CD276 promotes lipid metabolic reprogramming and regulates ferroptosis in clear cell renal cell carcinoma by upregulating FASN expression via SREBP1 - ZhiYu Zhang; Fan Zhang; YanHang Yu; ChuanAo Zhang; Jun OuYang (Human Cell, 2026)

Establishment of a patient-derived malignant peripheral nerve sheath tumor organoid model reveals SHH pathway activation and therapeutic vulnerability - Haruki Matsuoka; Keiichi Yoshida; Yukiko Matsuoka; Satoru Sasagawa; Noriko Nagamine; Yoji Kukita; Hideaki Sabe; Yusuke Yoshimura; Haruna Takami; Rie Suzuki; Hironari Tamiya; Shigeki Kakunaga; et al. (Human Cell, 2026)

Mitochondria and exosome intercellular co-transfer via annular gap junction vesicles in the human glioblastoma stem cell niche - Gabriel Arismendi-Morillo (Human Cell, 2026)

Chemotherapy-induced CAF-associated stromal remodeling in a humanized stroma pancreatic ductal adenocarcinoma organoid xenograft model: a comparison between GP and GS - Kaoru Furihata; Waka Iwashita; Atsushi Kurabayashi; Mutsuo Furihata; Kazushige Uchida; Keisuke Taniuchi (Human Cell, 2026)
Pancreatic ductal adenocarcinoma features a dense, desmoplastic tumor microenvironment (TME) dominated by cancer-associated fibroblasts (CAFs). While gemcitabine plus nab-paclitaxel (approximated as gemcitabine plus paclitaxel [GP]) and gemcitabine plus S-1 (GS) are standard regimens with distinct clinical indications, their specific effects on tumor suppression and CAF-associated stromal remodeling remain unclear. Using a humanized, three-dimensional (3D) S2-013 organoid xenograft model integrating human mesenchymal stem cells (MSCs) and human endothelial cells, we investigated the histopathological and immunohistochemical alterations induced by GP and GS. We quantitatively evaluated tumor parenchymal growth using cytokeratin 19 (CK19) and CAF-associated marker profiles, including α-smooth muscle actin (αSMA), fibroblast activation protein (FAP), platelet-derived growth factor receptors (PDGFR), and interleukin-6 (IL-6). Both regimens clearly suppressed tumor growth, but only GP significantly reduced parenchymal tumor growth compared with untreated controls. Notably, the treatments selectively remodeled the peritumoral stroma in the humanized xenograft model: PDGFR-expressing CAF-like cells were significantly reduced in the GP group, whereas FAP-expressing CAF-like cells and IL-6-expressing stromal cells were significantly decreased in the GS group. αSMA expression showed a general decreasing trend in both therapeutic arms. In summary, GP and GS chemotherapies induced distinct, measurable humanized TME remodeling modalities beyond direct cytotoxicity. By successfully recapitulating drug–stroma interactions and suggesting the human MSC origin of the peritumoral CAFs, this study demonstrates the robustness of our organoid xenograft model as a powerful preclinical screening platform for evaluating and predicting the efficacy of novel stroma-targeted and immunomodulatory investigative compounds.

Establishment of a ZFP64::NCOA3 fusion-positive spindle cell/sclerosing rhabdomyosarcoma organoid model and evaluation of fusion-gene dependency - Ryota Miyamoto; Keiichi Yoshida; Yukiko Matsuoka; Satoru Sasagawa; Noriko Nagamine; Yoji Kukita; Hideaki Sabe; Yusuke Yoshimura; Haruna Takami; Rie Suzuki; Hironari Tamiya; Shigeki Kakunaga; et al. (Human Cell, 2026)

Establishment and functional characterization of an EGFR-amplified tumoroid from squamous cell carcinoma of unknown primary - Miki Iwai; Etsuko Yokota; Takuro Yukawa; Kizuki Matsumoto; Takashi Urano; Kazutaka Nakashima; Hiroyoshi Doihara; Nagio Takigawa; Hideyo Fujiwara; Takashi Akiyama; Minoru Haisa; Yoshio Naomoto; et al. (Human Cell, 2026)
Carcinoma of unknown primary (CUP) remains a clinically challenging malignancy with limited treatment options and poor prognosis. Although genomic profiling has identified potentially actionable alterations, optimal therapeutic strategies are often unclear. Here, we report the establishment and characterization of a patient-derived tumoroid from an EGFR -amplified CUP and evaluate its utility as a functional model for therapeutic assessment. The patient-derived tumoroid (PDT-CUP#1) was successfully established from resected tumor tissue and maintained in long-term culture. Whole-exome sequencing demonstrated genomic concordance between the PDT-CUP#1 and the original tumor. Quantitative PCR and fluorescence in situ hybridization confirmed EGFR amplification. Xenograft tumors derived from PDT-CUP#1 recapitulated the histopathological features of the original lesion. Functional drug testing demonstrated differential sensitivity among EGFR-targeted agents. Whereas EGFR tyrosine kinase inhibition resulted in modest growth suppression, anti-EGFR monoclonal antibodies exhibited moderate antitumor effects, and an EGFR-targeted antibody–drug conjugate showed the most pronounced growth inhibition. Notably, the therapeutic sensitivity observed in the tumoroids was generally consistent with the patient’s clinical response to platinum-based chemotherapy combined with necitumumab. These findings demonstrate that a CUP-derived tumoroid can be successfully established while preserving the key molecular and pathological features of the original tumor. This model provides a platform for functional evaluation of therapeutic vulnerabilities and offers proof-of-concept for integrating patient-derived tumoroids into therapeutic decision-making in CUP.

Single-cell transcriptomics and functional analyses identified SPIN.DOC as a regulator for Wnt signaling and cancer stemness in colorectal cancer - Khuraijam Mrinalini Devi; Eshan Abbas; Thangjam Davis Singh; Rubismita Deka; Aditya Kumar; Lisam Shanjukumar Singh; Thiyam Ramsing Singh (Human Cell, 2026)

Integrative bulk and single-cell transcriptomics identify a recurrence-prognostic risk model with exploratory associations with treatment-response phenotypes in colorectal cancer - Shuai Li; Jingxian Li; Xianyue Bu; Mei Han; Ganggang Shi (Human Cell, 2026)

Correction: The dynamic evolution of circulating tumor cells during glecirasib treatment predicts survival and resistance in gastrointestinal tumors with KRASG12C mutation - Lei Jiang; Yiming Luo; Huan Liang; Xujiao Feng; Yan Huang; Yanyan Li; Zhenghang Wang; Ting Xu; Heng Zou; Zhi Li; Lin Shen; Yang Chen; et al. (Human Cell, 2026)

Exosomal miR-21-5p from ectopic endometrial stromal cells drives fibrosis progression in endometriosis through direct VHL targeting - Jia-Hao Chen; Yi-Hong Lei; Dian-Chao Lin; Hua-Ying Zhang; Zhi-Xiong Huang; Ruo-Fan Huang; Pei-Tong Wei; Meng-Jie Yang; Xin-Yu Ding; Wei-Dong Zhou; Qiong-Hua Chen (Human Cell, 2026)

A novel tRNA-derived fragment, tRF-19-79MP9PJZ, promotes uterine corpus endometrial carcinoma progression by targeting DSC3 - Huabo Jiang; Ting Jiang; Yuting Shen; Hongyan Jiang; Qing Yuan (Human Cell, 2026)
Uterine corpus endometrial carcinoma (UCEC) ranks as the 6th most common malignancy among women. Emerging evidence indicates that the dysregulation of tRNA-derived fragments (tRFs) is involved in the pathogenesis of multiple cancer types, including UCEC; however, the molecular mechanisms underlying the roles of tRFs in UCEC remain poorly characterized. Desmocollin3 (DSC3), a transmembrane protein, is predominantly expressed in the basal and suprabasal layers of normal stratified epithelia. While accumulating evidence has implicated DSC3 in the pathogenesis of multiple disease entities, its functional role in UCEC remains elusive. The present study is designed to investigate the functional significance and underlying molecular mechanisms of tRF-19-79MP9PJZ in the progression of UCEC. In this study, tRF-19-79MP9PJZ was found to be significantly upregulated in UCEC tissues and cell lines, with its elevated expression correlating with unfavorable prognostic outcomes in UCEC patients. Furthermore, tRF-19-79MP9PJZ knockdown was observed to suppress the proliferative and migratory capacities of UCEC cells, while concurrently enhancing apoptotic processes. At the mechanistic level, tRF-19-79MP9PJZ was demonstrated to facilitate UCEC progression through targeted regulation of DSC3. Collectively, this study elucidates a previously uncharacterized mechanism whereby tRF-19-79MP9PJZ drives UCEC development, thereby highlighting the potential of the tRF-19-79MP9PJZ/DSC3 axis as a therapeutic target for UCEC intervention.

HIPK2 exhibits context dependent dualistic effects and combinatorial inhibition of HIPK2-NLK-MAPK11 axis manifests synergism against gastric cancer - Aathithya Rangarajan; Thirumoorthi Natarajan; Sujatha Lakshminarayanan; Shirley SunderSingh; Jayavelu Subramani; Priya Ramanathan; Ramakrishnan Ayloor Seshadri; Gopal Gopisetty (Human Cell, 2026)

Exploring the role of CaMKII in exercise-induced cardioprotection - Yongchang Xu; Ziyu Liu; Xiaofeng Li (Human Cell, 2026)

"Indole-3-acetic acid promotes differentiation while suppressing proliferation in human intestinal epithelial cells": a Letter to the Editor - Johnny Padulo (Human Cell, 2026)

Colorectal cancer-derived exosomal ETS2 promotes macrophage M2 polarization by transcriptionally activating PRPF4 - Dengfeng Hou; Zhongyuan Bai; Jiaxin Zhao; Haipeng Fan; Junsheng Chen; Wenqi Bai (Human Cell, 2026)

Cytotoxic and genotoxic effects of oxime β-lapachone in human cancer cells: selectivity toward NCI-H460 and insights from molecular docking - Maria Francilene Souza Silva; Lara Polyana Silva Ramos; Fátima de Cássia Evangelista de Oliveira; Bruno Marques Soares; Daniel Pascoalino Pinheiro; Igor Frederico da Silveira Ramos; Rayran Walter Sousa; Victória Laysna dos Anjos Santos; Arlan de Assis Gonsalves; Paulo Michel Pinheiro Ferreira; Heurison Sousa e Silva; Cleônia Roberta de Melo Araújo; et al. (Human Cell, 2026)
β-Lapachone exhibits potent anticancer activity although its clinical application remains limited by toxicity and mechanisms of resistance. Therefore, structural modifications have been explored to improve its pharmacological profile. This study evaluated the cytotoxic, genotoxic, and toxicological effects of the oxime derivative β-lapachone oxime (Oxβ-Lp), together with its predicted pharmacokinetic properties and potential molecular interactions. Oxβ-Lp displayed cytotoxic activity against all tested cancer cell lines (NCI-H460, PC9, K562, and HepG2) after 72 h of exposure, with the greatest potency and selectivity observed in NCI-H460 non-small cell lung cancer cells (IC₅₀ = 1.88 µM; SI = 13.1). Mechanistic analyses demonstrated reduced cell viability, mitochondrial membrane depolarization, DNA damage, and induction of apoptosis, without significant cell cycle arrest. In Allium cepa , Oxβ-Lp did not alter the mitotic index or induce micronucleus formation but promoted chromosomal aberrations and DNA strand breaks. The Artemia salina assay indicated high acute toxicity (LC₅₀ = 16.80 µg/mL). Molecular docking suggested a potential interaction between Oxβ-Lp and NQO1, with binding energies comparable to those of dicoumarol and similar interaction patterns within the catalytic site. Overall, these findings demonstrate that Oxβ-Lp exhibits selective cytotoxicity against NCI-H460 cells and promotes apoptosis associated with mitochondrial dysfunction and DNA damage. Although the molecular mechanisms underlying its biological activity require further investigation, Oxβ-Lp represents a promising scaffold for developing novel anticancer agents.

Platelets as localized conduits of TGF-β1 in the tumor microenvironment: implications for cancer progression and therapy - Lulu Ji; Huitong Liu; Wei Zhu (Human Cell, 2026)

GATA6-mediated transcriptional activation and METTL3/IGF2BP2-dependent post-transcriptional stabilization upregulate CDC20 to promote the malignant progression of colorectal cancer and immune escape - Yuyu Wang; Xinfei Wang; Yongsheng Chang; Lu Yang; Daiyuan Dong; Yan Yang; Xiaohe Guo (Human Cell, 2026)

CCL21/CCR7 axis regulates VEGF-D m6A modification to drive lymphangiogenesis and lymphatic metastasis in gallbladder cancer - Zhenheng Wu; Xinran Cai; Lei Jiang; Bin Lin; Wei Pan; Shengzhe Lin; Yanling Chen; Haijie Hong (Human Cell, 2026)
Gallbladder cancer (GBC), the most common malignancy of the biliary tract, exhibits a high propensity for lymphatic system invasion. However, the mechanisms underlying lymphatic metastasis in GBC remain poorly understood. Here, we demonstrate that C–C motif chemokine ligand 21 (CCL21) is significantly upregulated in GBC and positively correlates with lymphatic vessel density and lymph node metastasis. Both in vivo and in vitro experiments confirm that CCL21/CCR7 axis promotes lymphangiogenesis and lymphatic metastasis in GBC. Mechanistically, CCL21/CCR7 modulates Vascular Endothelial Growth Factor-D (VEGF-D) mRNA N6-Methyladenosine (m 6 A) modification in an AlkB homolog 5 (ALKBH5)-dependent manner, thereby regulating VEGF-D protein expression. Site-directed mutagenesis experiments reveal that m 6 A modification sites in the coding sequence (CDS) region of VEGF-D mRNA are critical for VEGF-D protein regulation. Collectively, our findings highlight that CCL21/CCR7 regulates VEGF-D expression via m 6 A modification, driving lymphatic metastasis in GBC.

Comprehensive genomic analysis of five kindreds with multiple childhood leukemias: importance of individual functional analysis for rare ETV6 germline variants - Ai Yamada; Shun Nagasawa; Midori Nakagawa; Sachiyo Kamimura; Nami Inoue; Hiroyoshi Watanabe; Masatoshi Takagi; Yuhki Koga; Dai Keino; Hideki Nakayama; Jun Yoshimura; Koichiro Doi; et al. (Human Cell, 2026)
Germline variants in leukemia predisposition genes are increasingly detected in pediatric patients. Nevertheless, the rare variants identified in diagnostic samples may be misinterpreted without variant-level functional evaluation and cautious clinical interpretation. Whole-exome sequencing was performed on 28 individuals from five kindreds in which at least two children developed acute leukemia. Results identified a rare ETV6 variant, c.604C > G (p.Arg202Gly), in monozygotic twins with ETV6::RUNX1 -positive B-cell precursor acute lymphoblastic leukemia. To support variant interpretation, HeLa-cell populations stably expressing FLAG-tagged wild-type ETV6 and p.Arg202Gly and the known loss-of-function control p.Pro214Leu were established. Subcellular localization was assessed via immunofluorescence microscopy with quantitative scoring. Transcriptional repression was evaluated using luciferase reporter assays driven by ETV6 target promoters ( MMP 3 and PF4 ). p.Arg202Gly predominantly showed nuclear localization comparable to WT, whereas p.Pro214Leu was enriched in the cytoplasm. In the reporter assays, similar to WT, p.Arg202Gly retained repression activity. Meanwhile, p.Pro214Leu failed to repress both reporters. The in-silico prediction of nuclear export sequences suggested an additional export signal in p.Pro214Leu, but not in p.Arg202Gly. Collectively, these findings indicate that p.Arg202Gly behaves as WT-like in the assays performed and do not support a loss-of-function effect. Our study emphasizes the importance of variant-level functional assessment for rare ETV6 variants to inform clinical interpretation and avoid overestimation of pathogenicity.

Multi-organ transcriptome profiling in an isogenic cachexia-inducing xenograft model to dissect host responses across heart, liver, kidney, and muscle - Julia Osaki; Yomogi Shiota; Ikumi Fujita; Kazuyoshi Yanagihara; Tadashi Kondo (Human Cell, 2026)

SLC25A51 and mitochondrial NAD⁺ transport in acute myeloid leukemia: mechanisms, therapeutic potential, and translational perspectives - Chunmeng Rong; Ruixiu Chen; Hanqi Lou; Yongming Xia; Shiwei Duan (Human Cell, 2026)

Targeting eIF5A2 hypusination with bikinin sensitizes hepatocellular carcinoma to lenvatinib by suppressing TFEB-mediated autophagy - Shuqian Wang; Qingyun Zhou; Qiaomei Lin; Shufen Zhang; Ying Cai; Fangnan Wu; Fangyuan Kuang; Lianghui Wang; Shangzhi Xie; Jiahua Lan; Li Zheng; Guodong Xu; et al. (Human Cell, 2026)

Minimum reporting requirements for newly established human tumor-derived cell lines: a pragmatic checklist anchored to ICLAC, Cellosaurus/RRID, Nature Portfolio standards, and UKCCCR guidelines - Tadashi Kondo (Human Cell, 2026)

Mechanistic investigation of TRIB3-mediated growth, metastasis and ferroptosis in renal cell carcinoma - Wei Wang; Long Zhang; Tao Wu; Yuefeng Li; Haidong Wang; Haiqiao Huang; Yuexian Guo (Human Cell, 2026)

Matriptase proteolysis selectively drives disassembly and internalization of the claudin-7 complex while preserving E-cadherin - Yu-Ling A. Kao; He-Yu Huang; Yin S. Yu; Nanxi Huang; Ya-Chin Chan; Chen-Ray Lee; Michael D. Johnson; Chen-Yong Lin (Human Cell, 2026)

CDH2 marks a fibroblast-associated stromal cell state in pancreatic ductal adenocarcinoma - Yongjie Li; Ni Chen; Xin Deng; Liqun Wang (Human Cell, 2026)

Daucosterol linoleate from sweet potato inhibits breast cancer metastasis via SCD1 downregulation and suppression of epithelial-mesenchymal transition - Xintong He; Juan Li; Jun Lu; Zhaomin Chen; Ya Wang; Kehui He; Xuegang Li; Hang Ma; Xiaoli Ye (Human Cell, 2026)

Interaction of Listeria monocytogenes with the human choroid plexus endothelium in vitro: impact on invasion of the epithelium - Carolin Stump-Guthier; Sandrin Schulze; Walter Muranyi; Mobarak Abu Mraheil; Torsten Hain; Michael Hagmann; Hiroshi Ishikawa; Horst Schroten; Christian Schwerk; Stefan Weichert (Human Cell, 2026)
In the central nervous system (CNS), the highly vascularized choroid plexus (CP) produces the cerebrospinal fluid (CSF) and also acts as a blood-CSF barrier (BCSFB). Due to its location in the ventricular system of the brain, the CP can be used by pathogens such as bacteria to enter the CNS by crossing from the blood into the brain. This process, which can lead to meningitis, encephalitis and meningoencephalitis, is usually prevented by the BCSFB. Since barrier function is thought to be mainly executed by the CP epithelium, whose cells are connected to each other by dense tight junction (TJ) strands, in vitro studies of bacterial pathogens interacting with the BCSFB have routinely been performed using CP epithelial cells only. Recent data have shown that the CP endothelium can also contribute to barrier function at the BCSFB. Here, we used immortalized human CP endothelial cells (iHCPEnC) to investigate the interaction of the CP endothelium with the bacterial pathogen Listeria monocytogenes ( Lm ). Although Lm adhere to iHCPEnC, the endothelial cells are only weakly invaded by Lm , but readily transmigrated, in contrast to a CP epithelial cell line (HIBCPP cells). In a two-cell type model of the CP Lm transmigrated across iHCPEnC and invaded into HIBCPP cells, indicating that the CP endothelium does not pose a particularly strong barrier to Lm when attempting to overcome the BCSFB. Epithelial invasion was reduced compared to a model consisting of only HIBCPP cells, suggesting a regulatory impact of the CP endothelium.

Establishment and characterization of TRI-LC21: a novel patient-derived cell line of SMARCA4-deficient undifferentiated thoracic tumor - Shasha Li; Hao Luo; Dongsheng Wu; Yin Ku; Nanzhi Luo; Zhipeng Gong; Wenjing Zhou; Xinyi Xie; Guanyu Zhou; Yaohui Chen; Lunxu Liu (Human Cell, 2026)
SMARCA4-deficient thoracic undifferentiated tumor is a rare and highly aggressive subtype of lung cancer defined in the 2021 World Health Organization classification. Its scarcity and highly undifferentiated histology limit the availability of representative in vitro models and hinder therapeutic development. In this study, we established a novel cell line, TRI-LC21, from the primary tumor of a patient with lung cancer showing pathological features consistent with this entity. TRI-LC21 exhibited stable proliferation, strong colony-forming ability, and robust tumorigenicity in subcutaneous xenograft models. Xenograft tumors recapitulated the histological features and immunophenotype of the original tumor. Cell line authenticity was confirmed by short tandem repeat profiling, and mycoplasma contamination was excluded. Whole-exome sequencing revealed SMARCA4 loss accompanied by co-mutations in TP53 , STK11 , RBM10 , and ARHGAP35 . Transcriptome analysis demonstrated decreased expression of epithelial-associated genes and increased expression of stemness- and plasticity-related programs, consistent with an undifferentiated phenotype. Collectively, TRI-LC21 faithfully recapitulates the histological, immunophenotypic, and molecular characteristics of this tumor type and provides a valuable in vitro model for mechanistic investigation and preclinical studies.

PD-1/PD-L1 inhibitor induces systemic inflammation and alters cardiac lipid metabolism in C57BL/6 J mice - Cong Ye; Zhi-Ting Jiang; Chen Yan; Xin-Ran Li; Yu-Hua Zhu; Ling-Yu Zeng; Lan Luo (Human Cell, 2026)

A Cellosaurus-based systematic survey of sarcoma cell lines identifies critical gaps in public availability and priorities for future cell line development - Takashi Kondo; Tadashi Kondo (Human Cell, 2026)

The role of FOXM1 in tumor immunology: implications for cancer treatment strategies - Shuping Wang; Kaifeng Zhang; Tao Yong; Yu An; Shuang Bai; Chang Yuan; Huayong Liu; Tiange Liu; Zhipan Li (Human Cell, 2026)

Vascular reprogramming in cancer: engineering the tumor microenvironment - Yusuke Nishimura (Human Cell, 2026)

MiR-7-5p suppresses TGF-β-induced glycolysis and proliferation in intrahepatic cholangiocarcinoma by targeting MyD88 - Yi Tang; Zhenyong Tang; Rongjun Liu; Shaowei Xie; Bin Chen; Tao Huang; Xiang Huang; Dongyi Xie; Qiuhuan Zhang; Yuntian Tang (Human Cell, 2026)

Bone marrow mesenchymal stem cell-derived exosomes exert therapeutic effects on inflammatory bowel disease through miR-148a-3p/Ets-1-dependent inhibition of pyroptosis - Feilong Zhang; Ji Song; Yunjiao Zhang; Hejun Hu; Ping Zhou; Caixiao Xu; Meinan Zhan; Anna Hou; Xiangli Lin; Wenjuan Shen (Human Cell, 2026)

CNOT9 affects hepatocellular carcinoma proliferation and cell cycle through the PTEN/AKT/p53 signaling pathway - Zhiyao Zhang; Jihong Wang; Xinrui Du; Xin Liu; Jia Liu; Han Li; Yi Jiang; Kun He; Xiaojing Chen; Yunwei Han (Human Cell, 2026)

The dynamic evolution of circulating tumor cells during glecirasib treatment predicts survival and resistance in gastrointestinal tumors with KRASG12C mutation - Lei Jiang; Yiming Luo; Huan Liang; Xujiao Feng; Yan Huang; Yanyan Li; Zhenghang Wang; Ting Xu; Heng Zou; Zhi Li; Lin Shen; Yang Chen; et al. (Human Cell, 2026)

A model of Helicobacter infection using an artificial liver constructed by a radial-flow bioreactor - Kyoko Ito; Haruka Maehashi; Tomohiro Kato; Tomokazu Matsuura (Human Cell, 2026)
Helicobacter DNA has been detected in liver tissues from patients with hepatocellular carcinoma and other liver diseases, suggesting a potential involvement of Helicobacter infection in hepatic pathogenesis. However, whether Helicobacter pylori ( H. pylori ) can infect human hepatocytes and how such infection affects hepatocyte structure and function remain unclear. In this study, we used a three-dimensional (3D) bioartificial liver model reconstructed using radial-flow bioreactor technology to investigate the ability of H. pylori to infect hepatocytes and to characterize the cellular responses induced by infection. Histological analysis and electron microscopy demonstrated that H. pylori adhered to the hepatocyte surface and penetrated intercellular spaces. Infection significantly induced a threefold increase in apoptosis, accompanied by upregulation of TNF-α (1.5-fold) and activation of NF-κB (1.6-fold) (all P < 0.05). In addition, PCNA expression significantly decreased to approximately 60% of control levels ( P < 0.05), whereas Akt activation was enhanced and β-catenin was predominantly localized in the cytoplasm. No significant differences were observed in Ki-67, IL-8, Ets-1, or c-Met expression compared with controls. These findings demonstrate that H. pylori can infect the 3D liver model and induce apoptosis and signaling alterations in hepatocytes, suggesting a potential pathological impact on the liver. Further studies are required to determine whether similar effects occur in the human liver in vivo.

TRERNA1-mediated acetylation represses ferroptosis of non-small cell lung cancer cells via the KAT6A/H3K23ac/TRIM24-PIK3CA pathway - Bobo Li; Yulan Sun (Human Cell, 2026)

When fatty liver fuels kidney cancer: the THRB connection - Amr Ahmed El-Arabey; Osama Ahmed Elsayed (Human Cell, 2026)

BASP1 promotes breast cancer progression and shapes an immunosuppressive microenvironment by recruiting MDSCs and suppressing T cell function - Haijie Hu; Xiaomin Feng; Zhi’an Yan; Fuzhong Qi; Donghai Li; Xuegang Luo (Human Cell, 2026)

A novel HPV E6/E7-regulated long noncoding RNA CRL suppresses cervical intraepithelial neoplasia progression by attenuating ferroptosis - Ting Zhang; Yanan Yan; Shuai Yuan; Tianqi Yang; Can Shi (Human Cell, 2026)

Effects of ABCG2 dysfunction on hyperuricemia progression in premenopausal and postmenopausal women - Yuka Miyoshi; Akiyoshi Nakayama; Hiroshi Nakashima; Itsumi Hashimoto; Yusuke Kawamura; Seiko Shimizu; Yu Toyoda; Tomoko Mizuno; Risa Tanabe; Yoshinobu Hamada; Mako Nagayoshi; Yoko Kubo; et al. (Human Cell, 2026)
Serum uric acid (SUA) levels are influenced by environmental and genetic factors, such as sex and ABCG2 variants. Their poorlyunderstood links to menstrual status prompted us to conduct this study to evaluate the effects of menstrual status-related ABCG2 function, detectable from the presence of its dysfunctional variants, on SUA levels. Recruited for the present study were 9244 Japanese individuals, comprising 4466 women and 4778 men. We evaluated the effect size on SUA and population attributable fractions (PAFs) for hyperuricemia progression based on factors, including ABCG2 function, BMI, alcohol consumption, age, and menstrual status (in women). The results, from the viewpoint of SUA increase, showed a 25% ABCG2 dysfunction to be equivalent to the effects of a 1.67 kg/m 2 increase in BMI, alcohol consumption of 154.2 g/week, an 18.6-year increase in age, and, in women, 42.7% due to menopause. In the tested female sample, the PAF for hyperuricemia due to ABCG2 dysfunction (32.8%) exceeded those for overweight/obesity (19.5%) and aging (28.7%). Menopausal status exhibited the highest PAF at 63.0%. In premenopausal individuals, the PAF for ABCG2 dysfunction was 45.8%, much higher than that after menopause (29.6%). Although premenopausal women generally had a lower prevalence of hyperuricemia than postmenopausal individuals, those with dysfunctional variants of ABCG2 tended to show a higher SUA increase and PAFs in premenopausal than in postmenopausal women. These results indicate that genetic testing might be helpful in preventing and treating hyperuricemia, particularly for those with higher SUA before menopause, in both individuals and in populations as a whole.

BMAL1 regulates the initial step of embryo implantation by modulating endometrial cell adhesion and migration - Keita Imai; Yidan Dai; Masanori Ono; Yoshinari Imai; Junya Kojima; Tomoko Fujiwara; Takiko Daikoku; Yoshiko Maida; Hitoshi Ando; Hiroshi Fujiwara; Hirotaka Nishi (Human Cell, 2026)

Indole-3-acetic acid promotes differentiation while suppressing proliferation in human intestinal epithelial cells - Marta Mallardo; Furqan Memon; Raffaella Pagliaro; Aurora Daniele; Ersilia Nigro (Human Cell, 2026)

The potential of bioengineered exosomes in regenerative medicine: a next generation therapy - Shiwani Kumari; Anjali Agnihotri; Arpit Sharma; Shweta Dongre; Ashwani Tiwari; Naveen Soni; Bhawana Bissa (Human Cell, 2026)

Immune imbalance in rheumatoid arthritis: insights from γδ T cell receptor phenotyping - Sylwia Biały; Joanna Wielińska; Kinga Maria Tyczyńska; Jerzy Świerkot; Katarzyna Bogunia-Kubik (Human Cell, 2026)
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction. While conventional αβ T cells have been extensively studied, the contribution of γδ T cells to RA pathogenesis remains insufficiently understood. Unlike αβ T cells, γδ T cells recognize antigens independently of major histocompatibility complex (MHC) restriction, and their surface receptor expression plays a pivotal role in regulating effector functions. This study aimed to investigate the phenotype and surface receptor profile of γδ T cells in RA patients undergoing anti-TNF therapy, to better understand their potential immunoregulatory and prognostic significance. Peripheral blood samples were collected from RA patients before and during treatment with TNF inhibitors, as well as from healthy controls. Flow cytometry was used to quantify γδ T cell frequency and to assess the expression of selected activation, differentiation, and exhaustion markers on their surface. RA patients exhibited a significant reduction in the frequency of circulating γδ T cells compared with healthy controls. Moreover, γδ T cells in RA displayed phenotypic features of advanced differentiation and functional exhaustion, including altered expression of key surface receptors. The observed alterations in γδ T cell phenotype and receptor expression suggest chronic immune activation in RA. These findings highlight the potential of γδ T cell surface markers as candidate biomarkers for disease activity and response to anti-TNF therapy.

Thiolutin attenuates neuroinflammation and neuronal apoptosis by suppressing microglial pyroptosis through NLRP3 inflammasome inhibition after spinal cord injury - Yifan Zeng; Lijuan Zhao; Shuxia Qian (Human Cell, 2026)

FUS modulates R-loops by functionally interacting with RNase H1 - Anusree Dey; Rituparna Das; Sheetal Uppal (Human Cell, 2026)

Integrative analysis of lncRNAs associated with disulfidptosis-related genes for prognostic risk evaluation and tumor immune microenvironment assessment in laryngeal squamous cell carcinoma - Qinghua Liu; Zesheng Zhang; Yingli Xie; Ru Tang; Ge Gao; Zhe Yang; Duanshali Liu; Yilun Zou; Yongxia Zhang; Mingbo Liu (Human Cell, 2026)

miR-141-5p positively regulates ACVRL1 expression to promote cervical cancer progression - Jianbing Liu; Yongzhi Jiao; Jinjuan Wang; Xiaohua Cui; Ying Gao; Yan Zhang; Jing Xu; Jianqing Hao; Yongli Hou; Wei Wang; Guang Yang; Li Li (Human Cell, 2026)

Histone H4K5 deacetylation by enhanced HDAC1 expression drives endothelial inflammation in diabetes through repression of the KLF2-eNOS axis - Srinjoy Chakraborty; Vivek Akhouri; Yash Tushar Katakia; Shyam Kumar Ramakrishnan; Anil Bhanudas Gaikwad; Syamantak Majumder (Human Cell, 2026)

miR-16-2-3p enhances glucocorticoid sensitivity in ulcerative colitis by targeting CREB1 and NF-κB1 - Tianfeng Yang; Juan Luo; Junrui Tang; Jing Wu; Shuxian Xia; Maojuan Li; Qi Huang; Gang Yang; Jiarong Miao; Yunzhen Zhu (Human Cell, 2026)

Gata1-mediated Hras transcription stimulates blood-brain barrier injury in ischemic stroke through activation of the ERK pathway - Kelong Chen; Ling Chen; Huijing Sun; Bin Li (Human Cell, 2026)

NOTCH3 signal activation by its extracellular domain accumulation in an iPSC line newly established from a CADASIL patient - Ruihua Sun; Zhenxiang Zhao; Ningning Che; Ning Liu; Xiaoyi Ji; Anqi Li; Fengyu Wang; Junkui Shang; Jiewen Zhang (Human Cell, 2026)

METTL14 promotes trophoblast dysfunction by elevating SZRD1 expression in an m6A-dependent manner - Qinglan Ye; Liyong Deng (Human Cell, 2026)

Bisphosphoglycerate mutase is involved in glucose metabolism and progression of nonalcoholic fatty liver disease based on liver organoids - Zheng Zhou; Xiyan Zheng; Xianqing Chen; Maoyun Xie; Fei Du; Zhiqun Lin; Xianjie Shi (Human Cell, 2026)

NR1H4 downregulation facilitates abnormal cell proliferation contributing to IgA nephropathy pathogenesis, with potential clinical implications - Xian Li; Wen Yang; Changxi Sun (Human Cell, 2026)

Deciphering the immunological landscape of HR + metastatic breast cancer: insights from single-cell transcriptomics - Lifang He; Qianqian Zhao; Zexiao Chen; Lijuan He; Zhaochang Qi; Jundong Wu; Kexiang Zhou; Yukun Cui (Human Cell, 2026)
Breast cancer remains the leading cause of cancer-related mortality among women worldwide, primarily due to metastatic complications. The immune components of the tumor microenvironment (TME) significantly influence metastatic progression. The objective of this study was to uniquely characterize the TME of hormone receptor-positive (HR +) breast cancer with a focus on ovarian metastasis using single-cell RNA sequencing. We delineated the cellular architecture of breast cancer tissues. A total of 9 cell types in 18 clusters were identified, including T cell, B cell and plasma, macrophage, neutrophil, fibroblast, macrophage, endothelial, basal, luminal, SMC (smooth muscle cells) and proliferation cells. Furthermore, macrophages were divided into tumor-associated macrophages and monocyte macrophages, with detailed marker gene analysis. Key statistical findings include the identification of five critical genes (GPR183, BHLHE41, CD83, SLC25A37, and SELL) associated with macrophage functionality. In vivo validation using immunohistochemistry on clinical samples from 10 breast cancer patients with ovarian metastases confirmed that GPR183, BHLHE41, and CD83 were highly expressed in tumor tissues, while SLC25A37 and SELL were highly expressed in adjacent normal tissues. Furthermore, survival analysis correlated the expression levels of these genes with patient outcomes, thus presenting potential prognostic biomarkers. Our study contributes to a deeper insight of the tumor microenvironment in HR + metastatic breast cancer, and offers potential targets for developing novel therapeutic interventions aimed at mitigating metastatic progression and improving clinical outcomes for HR + breast cancer patients.

Transcriptomic landscape of oral potentially malignant disorders: a meta-analysis approach - Vaishnav Vasudevan; Gangotri Siddappa; Reba Elsa Sam; H. K. Madhumathi; Anela Thomas; Sumsum P. Sunny; Vivek Shetty; Vidya Bhushan; Yogesh Dokhe; Vijay Pillai; Praveen Birur; Moni A. Kuriakose; et al. (Human Cell, 2026)

Heterogeneity of HTLV-1 proviral integration sites and internal structures in the ATL cell line MT-1 - Misaki Izaki; Yuki Hashikura; Kunihiko Umekita; Kazumi Umeki; Taiga Miyazaki (Human Cell, 2026)
Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL). The ATL-derived cell line MT-1 is used to study HTLV-1 biology and leukemogenesis. However, the proviral integration sites and internal structures of HTLV-1 are not comprehensively characterized in MT-1 cells. We analyzed two independently maintained MT-1 cell lines (MT-1 J and MT-1 M) using long PCR, quantitative PCR-based proviral load analysis, inverse long PCR, inverse PCR, integration site-specific PCR, direct sequencing, and Rapid Amplification of Integration Site without Interference by Genomic DNA contamination. Long PCR and proviral load analyses demonstrated that MT-1 cells harbor multiple full-length and defective HTLV-1 proviruses. MT-1 J cells exhibited reduced proviral load in the pX region, suggesting the presence of pX -lacking proviruses. Inverse long PCR and inverse PCR revealed at least five proviral integration sites in MT-1 J cells; MT-1 M cells contained three. Site-specific PCR confirmed the differential preservation of integration sites. Sequence analysis revealed two full-length proviruses and three type I defective proviruses with distinct internal deletions, including an unreported provirus with a large deletion encompassing pX . Rapid Amplification of Integration Site without Interference by Genomic DNA contamination identified major proviral clones shared between MT-1 J and MT-1 M cells, while revealing differences in clone frequencies and minor integration sites. The MT-1 cell line is a polyclonal population containing multiple full-length and defective HTLV-1 proviruses. Its proviral composition can change during long-term in vitro passaging. This heterogeneity should be considered when interpreting results obtained using MT-1 cells in HTLV-1 and ATL research.

Establishment and characterization of a novel HBV-integrated hepatic sarcomatoid carcinoma cell line - Jiayin Dai; Fang Cao; Zhenli Yang; Kun Dong; Xiaozheng Huang; Xiaocui Bian; Yuqin Liu (Human Cell, 2026)

Culture-dependent baseline states and drug response programs in myxofibrosarcoma models across 2D and 3D systems - Yuki Yoshimatsu; Yomogi Shiota; Tadashi Kondo (Human Cell, 2026)

Generation of a human-induced pluripotent stem cell line from a retinitis pigmentosa patient carrying biallelic mutations in EYS gene - Jueun Kim; Juyeong Yu; Donghyun Kim; Borami Shin; Johnny Kim; Yong Soo Park; Kee-Pyo Kim (Human Cell, 2026)

Human peritoneal CCR2LowCRIgHigh macrophage subset exhibits embryonic origin-like phenotypes - Naofumi Takahashi; Sara A. Habash; Yoshihiro Komohara; Shingo Usuki; Kei-ichiro Yasunaga; Shinjiro Hino; Randa A. Abdelnaser; Thorbjorg Einarsdottir; Takushi Nomura; Atsuko Yonemura; Takatsugu Ishimoto; Shinya Suzu (Human Cell, 2026)

Pathogenesis and therapeutic strategies for neuropsychiatric lupus centered on innate immune activation - Wataru Nagata; Toshiaki Ishizuka (Human Cell, 2026)
Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious central nervous system complication of systemic lupus erythematosus (SLE) that markedly reduces patient quality of life. Despite its clinical importance, the underlying mechanisms remain incompletely defined, and effective treatments are limited. In this review, we synthesize preclinical and clinical evidence that aberrant activation of innate immunity by self-nucleic acids and consequent overproduction of Type I interferons (IFN-I) constitute a central pathogenic axis in NPSLE. IFN-I and other inflammatory mediators promote disruption of the blood–brain barrier (BBB), enabling entry of autoantibodies, cytokines, and immune cells into the brain. These factors, together with damage-associated molecular patterns, activate microglia and astrocytes, driving sustained neuroinflammation that provokes synaptic loss, neurotransmitter dysregulation, excitotoxic neuronal injury, impaired neurogenesis, and mitochondrial dysfunction—mechanisms that underlie cognitive impairment, mood disorders, and other neuropsychiatric manifestations. We review therapeutic strategies targeting each step of this cascade, including blockade of IFN-I signaling (e.g., anifrolumab), inhibition of endosomal nucleic acid sensing (TLR antagonists), cytokine and JAK inhibition, modulation of microglial function (CSF1R inhibitors), and approaches to protect or restore BBB integrity (e.g., statins). Finally, we discuss biomarker-guided patient stratification and trial designs necessary to address NPSLE heterogeneity and accelerate the development of personalized therapies. By elucidating the cellular responses of the neurovascular unit to innate immune insults, this review provides a molecular framework for developing targeted therapies for NPSLE.

Extracellular vesicle-derived CDCP1 promotes chemoresistance and macrophage polarization in breast cancer - Yibing Liu; Li Ma; Ting Zhu; Di Wu; Yonglei Liu (Human Cell, 2026)

Ethanol-induced NINJ1 oligomerization might contribute to the lytic death of granulosa cells in PCOS - Caglar Berkel (Human Cell, 2026)

Exploring the role of protein homeostasis regulation in glycolysis in head and neck tumors - Tian Xia; Kunya Jiang; Qinghong Huang; Yuxiang Luo; Leifeng Chen; Debin Xu (Human Cell, 2026)

Pathological and therapeutic implications of Notch overexpression in claudin-low breast cancers - Reena Yadav; Sumit Goel; Deepinder Kaur; Laxmi Kumari; Divya Dahiya; Amanjit Bal; Alka Bhatia (Human Cell, 2026)

AKR1B10 drives hepatic steatosis and inflammation in metabolic dysfunction-associated steatotic liver disease via PI3K/AKT-mediated autophagy suppression - Na Nie; Jing Tian; Xiaoyan Dong (Human Cell, 2026)

Induction of activating transcription factor 3 (ATF3) in the cerebral cortex of a mouse model of blast-induced traumatic brain injury - Arumu Endo; Yasushi Satoh; Minori Koga; Wataru Nagata; Ken Yokochi; Fumiho Asai; Akihiro Ebihara; Tomohiro Tsuru; Yoshiyuki Araki; Masashi Kashitani; Hiroyuki Toda; Nozomi Ito; et al. (Human Cell, 2026)
Traumatic brain injury (TBI) is a leading cause of long-term disabilities and mortality worldwide. Blast-induced TBI (bTBI) is the injury most commonly sustained by military personnel, but the pathomechanisms are largely unknown. Recently, accumulating evidence has suggested that neuroinflammation, characterized by the activation of microglia and astrocytes and elevated production of inflammatory mediators such as interleukins, cytokines, and chemotactic cytokines (chemokines), is a key pathological feature in bTBI. Therefore, controlling excessive neuroinflammation is critical to improve long-term neurological outcomes after bTBI, so understanding the mechanism of the neuroinflammation in bTBI is of significant interest. Activating transcription factor 3 (ATF3) is one of the most important transcription factors that regulate local and systemic inflammation in multiple pathophysiological processes such as cardiovascular disease, dementia, and ischemia/reperfusion-induced damage. Recently, ATF3 has attracted much attention for involvement in the neuroinflammatory response, by regulating the production of neuroinflammatory mediators, in a weight-drop–based TBI model. In this model, the upregulation of Atf3 messenger ribonucleic acid (mRNA) levels was rapidly induced with the strongest increase at 1–2 h and decline by 4 h post-injury. However, there is little information about ATF3 in bTBI, and thus, the present study examined the expression of ATF3 in a mouse bTBI model. We here show the significant upregulation of Atf3 mRNA was not observed in the cerebral cortex at 2 h post-exposure. However, the upregulation was observed at 5 days post-injury. Our results suggest robust differences in time course of neuroinflammation between other non-blast and blast TBIs.

An overview of the developments in 3D cancer cell models, assay techniques, and imaging modalities - Nicola H. Wheeler; Kayode A. Dada; Carrie A. Minnaar (Human Cell, 2026)
Cancer biology is a constantly evolving field of study due to the dynamic and complex nature of biological systems. The unique role of in vitro assays in cell biology has led to numerous transformations in our understanding of the functional and structural details of the cells and tissues that comprise these systems. However, the traditional monolayer assays have been reported to fall short of the in vivo physiology of cells. This has led to the development of 3D cell models, such as spheroids and organoids, that aim to recapitulate the intricate structural and functional behaviour of in vivo tumours. This review describes passive methods of spheroid formation (scaffold-free and scaffold-based) and the limitations that have driven the development of engineered active design methods to increase the physiological relevance of the model. Traditional assays need to be modified to evaluate these models, accounting for their architecture, density, and microenvironment gradients. Current developments in performing 3D cell assays include increased reagent concentration and incubation periods; however, many protocols still require single-cell analysis. We present a review of assay developments that maintain the spatial and contextual information that makes the 3D models physiologically relevant. Additionally, we introduce the advances in microscopy techniques that provide deeper visualisation of these models.

Ubiquitously expressed prefoldin-like chaperone (UXT) regulates putrescine metabolism and promotes colorectal cancer progression - Ming Chen; Shisi Huang; Lu Gong; Xingcheng Wu; Ying Li; Hanbing Wu (Human Cell, 2026)

Advancing diagnostic biomarkers in Alzheimer’s disease: interdisciplinary innovations and technological frontiers - Faheem Patwekar; Mohsina Patwekar; Lee Seong wei; Rohit Sharma; Ryan Varghese; Arifullah Mohammed (Human Cell, 2026)

CBC3T-3: a novel patient-derived cisplatin-resistant distal cholangiocarcinoma cell line harboring multiple TP53 missense mutations - Jiahui Xi; Mingzhen Bai; Ruyang Zhong; Chongfei Huang; Ruoshui An; Long Gao; Haidong Ma; Liang Tian; Jinyu Zhao; Ningzu Jiang; Xiang He; Leiqing Wang; et al. (Human Cell, 2026)
Distal cholangiocarcinoma (dCCA) is a malignant tumor characterized by a challenging diagnosis, high invasiveness, and extremely poor prognosis. Research on dCCA is limited by the scarcity of reliable patient-derived preclinical tumor models. This study established a novel human distal cholangiocarcinoma cell line, CBC3T-3, and systematically characterized its biological properties, genomic features, and potential for clinical application. This cell line was extracted from postoperative distal cholangiocarcinoma tumor from a 54-year-old male patient. It was stably passaged (> 50 generations) through primary culture and condition optimization, preserving the same pathology as that of the primary tumor. Whole-exome sequencing (WES) confirmed somatic mutations, tumor mutation burden, single-sample clonal structure, driver genes, and drug resistance genes in CBC3T-3 cells, revealing their genomic characteristics. Functional assays demonstrated that CBC3T-3 cells exhibit strong capabilities for proliferation, migration, and invasion in vitro. In a subcutaneous xenograft model in immunodeficient mice, palpable tumor nodules developed within 4 weeks, reflecting the clinical characteristics of rapidly progressive disease. Drug sensitivity analysis revealed that, compared with TFK-1 cells, CBC3T-3 cells presented significantly greater responses to paclitaxel, gemcitabine, and oxaliplatin but relatively poor responses to 5-FU and cisplatin. The integration of drug resistance gene findings from WES suggests that TP53 missense mutations may mediate primary resistance to cisplatin. The establishment of the CBC3T-3 cell line enhances the research toolkit for dCCA. Its genomic characteristics and functional plasticity provide a reliable preclinical tumor model for developing precision therapies and investigating drug resistance mechanisms.

Arginine deprivation induces ROS dependent autophagic cell death in human acute myeloid leukemia cells - Fatima Taki; Mirna Farhat; Oula El-Atat; Sarah Al-Samman; Nicole Assaf; Ralph J. Abi-Habib (Human Cell, 2026)

Rolled amniotic membrane for practical vascular graft development: a scoping review - Ahmad Hafiz Murtadha; Nur Najmi Mohamad Anuar; Mohamad Fikeri Ishak; Muhammad Dain Yazid; Nadiah Sulaiman (Human Cell, 2026)

Unveiling TNFRSF19: a novel tumor suppressor targeting endoplasmic reticulum stress and LGR5/Wnt/β-catenin in cervical cancer - Xing Wei; Lili Su; Ran Chen; Tingting He; Changyi Wu (Human Cell, 2026)

Femtosecond label-free imaging evaluates the metabolism of mesenchymal stromal cells - Jiawei Liu; Yang Liu; Benhan Xiong; Hu Cao; Xue Li; Chunyan Tian; Hua Wang (Human Cell, 2026)

Establishment and characterization of NCC-GCTB16-C1: novel patient-derived cell line of giant cell tumor of bone - Kenta Kono; Yomogi Shiota; Julia Osaki; Ting-Ting Shu; Satoshi Kamio; Shintaro Iwata; Shogo Nishino; Akihiko Yoshida; Sumio Ohtsuki; Seiji Ohtori; Akira Kawai; Tadashi Kondo (Human Cell, 2026)

Herbacetin alleviates acute doxorubicin cardiotoxicity via regulating the ERK1/2-FOXO3a signaling pathway - Sijia Bian; Xinran Li; Peiyan Zhu; Zhiting Jiang; Chen Yan; Shuling Wei; Liqi Luo; Yuhua Zhu; Lan Luo (Human Cell, 2026)

The sialyltransferase ST3GAL1 mediates MUCL1 sialylation to exacerbate breast cancer progression - Can Cui; Jing Feng; Boyu Shang; Qingxin Guo; Shuren Wang; Qi Wang; Fumin Cheng; Yi Zhou (Human Cell, 2026)

DKK1 exacerbates dental pulp inflammation: insights from RNA-sequencing analysis - Qiting Liang; Jingyi Ding; Jiayan Xie; Yongying Chen; Wanting Su; Chufang Liao (Human Cell, 2026)

MKRN2 enhances hepatocellular carcinoma proliferation through the p38 MAPK pathway - Xiaojing Chen; Zihan Yan; Xinrui Du; Zhiyao Zhang; Xin Liu; Jing Zhang; Lanxin Hu; Kun He; Jihong Wang; Yunwei Han (Human Cell, 2026)

5-Azacytidine induces sensory hair cell marker expression in human inner ear cells in vitro - Meng Deng; Zhengqing Hu (Human Cell, 2026)

Establishment and characterization of a novel sinonasal adenosquamous carcinoma cell line, TC717, with a high tumor mutational burden - Ryosuke Kuga; Takeo Yamamoto; Takeshi Iwasaki; Midori Taniguchi; Tomomi Manako; Hidetaka Yamamoto; Yoshinao Oda (Human Cell, 2026)

The role of macrophages in peritoneal dialysis-associated peritoneal fibrosis - Jianqiang Shu; Zhikang Sun; Wenwen Zhao; Yixiao Zhu; Qinglian Wang (Human Cell, 2026)

SIRT1 reduced DDX5 neddylation to attenuate myocardial ischemia/reperfusion injury - Yan Liang; Gongcheng Huang; Xiaohua Zhu; Chen Huang; Hai Liu; Liliang Shu (Human Cell, 2026)

Conditioned medium from human adipose-derived mesenchymal stromal cells can modulate cell migration and morphology of keratinocytes in vitro - Cristiano Rodrigues; Thaís Casagrande Paim; Carla Zanatelli; Elisa Vasconcellos Soares Prignon; Jéssica Gonçalves Azevedo; Liliana Ivet Sous Naasani; Márcia Rosângela Wink (Human Cell, 2026)
The regenerative ability of the skin is orchestrated by different types of cells, including mesenchymal stromal cells (MSCs). Their role in wound healing is being widely studied due to their capacity to produce a secretome able to modulate their microenvironment. In this context, MSCs factors can be isolated using in vitro cell culture and be experimentally tested for a series of clinical conditions, such as skin repair. In this study, we produced conditioned medium (MSC-CM) using primary cultures from human adipose-derived MSCs. This medium was used as treatment in a culture of keratinocytes cell line from adult human skin (HaCaT) to investigate the modulation of their dynamics. We analyzed cell proliferation, migration, and changes on cell morphology by labeling the actin filaments and nuclei. The factors released by MSCs were able to improve both the proliferation and migration of keratinocytes. In addition, there was an increase in the amount of actin stress fibers, filopodia protrusions, and nuclei irregularities. The MSCs secretome modified the migratory patterns of keratinocytes, being observable through their morphological changes. At least in part, this modulation was caused by the TGF-β1 signaling, considering that its antagonist, SB 431542, lead to a reduction of approximately 76% in the migration of HaCaT cells through the porous membranes of transwell chambers. Together, our data contribute to a better understanding of the role of MSCs on keratinocytes during wound healing and reinforce the importance to investigate their potential in dermal regeneration therapies.

The interplay between circadian rhythm components and apoptosis in health and disease - Mohammad Rafi Khezri; Somayeh Mohammadi Panah; Morteza Ghasemnejad-Berenji; Hojat Ghasemnejad-Berenji; Saeed Mehrzadi; Amin Abdollahzade Fard; Aysa Rezabakhsh; Maryam Rahnama (Human Cell, 2026)

Construction of a risk model based on exosome-related genes predict clinical prognosis and therapeutic response and revealing TIMP1 as a promising target in colorectal cancer - Xinyu Gao; Te Zhang; Tianhao Li; Yongdan Zhang; Xipeng Zhang; Haoren Jing (Human Cell, 2026)

The Hippo pathway in cardiac fibrosis: mechanisms and therapeutic prospects - Yuting Qiu; Shanshan Hu; Hui Li; Jiatong Ren; Meixi Liao; Jie Huo; Zenan Luo; Lili Lu (Human Cell, 2026)

Hsa_circ_0003176: a key player in the m6A modification-mediated regulation of autophagy and glycolysis in cisplatin-resistant non-small cell lung cancer - Sujuan Guo; Zhicheng Yang; Jiajie Qiao; Lei Rong (Human Cell, 2026)

Ethambutol induces optic neuropathy through SDHB-mediated ferroptosis in retinal ganglion cells via Smad4 pathway - Qiushi Li; Wei Ge; Yifan Zhang; Qibin Xu; Junli Xu; Yu Zhang; Xingneng Guo; Wenyan Sheng; Liwei Zhu (Human Cell, 2026)
Ethambutol (EMB)-induced optic neuropathy (EON) is a clinical concern. Ferroptosis, involving iron and toxic reactive oxygen species (ROS), causes unique cell death, but its mechanism in EON is unclear. This study aims to explore the EON mechanisms. Wistar rats were used to establish an EON model by administering EMB at 50 mg/kg daily for 8 weeks. Retinal ganglion cells (RGC-5 cells) were used for in vitro experiments. Histological staining, MTT assays, flow cytometry, western blot analysis, dual-luciferase reporter assay, chromatin immunoprecipitation, and high-throughput sequencing were conducted to investigate cell death modes and molecular changes. EMB treatment leads to significant cell loss and structural damage in RGCs of EON model, predominantly through ferroptosis. We confirm increased ROS levels, downregulation of SLC7A11 and GPX4, and decreased glutathione (GSH) levels, upregulation of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) levels in EMB-treated RGC-5 cells. Furthermore, sequencing data reveal that in RGC-5 cells treated with EMB, the differentially expressed genes (DEGs) primarily exhibited alterations in biological functions associated with metabolism, stress response, and apoptotic regulation. Specifically, EMB inhibits the expression of succinate dehydrogenase enzyme B (SDHB), thereby disrupting antioxidant defenses and facilitating ferroptosis. Moreover, Smad4 has been pinpointed as a pivotal transcription factor in regulating SDHB expression. Notably, its interaction with the promoter region of SDHB is inhibited by EMB. This study provides compelling evidence for the involvement of ferroptosis in EON and highlights SDHB and Smad4 as potential therapeutic targets for mitigating this adverse effect.

Chebulagic acid targets FBXO38 to enhance natural killer cell-mediated anti-tumor immunity in lung adenocarcinoma - Xiwen Hu; Rui Sha; Feiran Yang; Jinwen Chai; Bin Liu; Xiaoqing Xu (Human Cell, 2026)

Histone deacetylase 3 promotes hypoxia-induced human pulmonary arterial smooth muscle cell proliferation by modulating the CSF2-JAK2-STAT5 signaling pathway - Jie Zhang; Youfei Fan; Yanting Gao; Youpeng Jin (Human Cell, 2026)
The growth of human pulmonary arterial smooth muscle cells (hPASMCs) is one of the key contributors to vascular remodeling in pulmonary arterial hypertension (PAH). Although histone deacetylase 3 (HDAC3) has been implicated in acute lung injury and pulmonary fibrosis, its role in hypoxia-induced PAH remains unclear. Here, the function and associated mechanisms of HDAC3 in hypoxia-induced hPASMC proliferation were investigated. A hypoxia-induced hPASMC model was constructed to evaluate the role of HDAC3 in cell proliferation under hypoxic conditions. The effects of HDAC3 siRNA and ruxolitinib, a JAK pathway inhibitor, were assessed to explore the regulatory mechanism of HDAC3 in vascular remodeling. Hypoxia significantly upregulated both HDAC3 mRNA and protein. Inhibition of HDAC3 attenuated hypoxia-induced proliferation in hPASMCs. Moreover, HDAC3 inhibition downregulated CSF2 and suppressed proliferation by inactivating the JAK2/STAT5 axis. In contrast, HDAC3 overexpression enhanced CSF2 expression, activated JAK2/STAT5, and promoted hPASMCs’ proliferation under hypoxia. Notably, the pro-proliferative and pathway-activating effects of HDAC3 overexpression were reversed by CSF2 silencing or ruxolitinib treatment. HDAC3 plays a key role in hypoxia-induced hPASMC dysfunction. Its inhibition mitigates aberrant proliferation through a CSF2-dependent inactivation of the JAK2/STAT5 pathway under hypoxia. These results indicate the potential of using HDAC3 for treating hypoxia-induced PAH.

Generation and characterization of human iPSC lines (FAHZJUi001-A and FAHZJUi002-A) from two familial recurrent hydatidiform mole patients carrying homozygous mutation in the NLRP7 gene - Limeng Cai; Jiayang Wan; Yating Zhao; Yuyan Xu; Luya Cai; Li Zhang; Tingyu Gong; Jin Zhang; Jianhua Qian (Human Cell, 2026)

Normal human cell strains characterized by the properties of mesenchymal stromal cells: implications for the fundamental features of cultured cells - Fumio Kasai; Keisuke Fukumoto; Kaoru Saijo; Kazuaki Nakamura; Yohei Miyagi (Human Cell, 2026)

The role of TLR2/MyD88/NF-κB pathway-mediated macrophage M1 polarization in recurrent spontaneous abortion associated with antiphospholipid syndrome - Xiaolan Huang; Shuyin Zhang; Danhong Liang; Bingbing Huang; Jing Chen; Xiaoqing Chen (Human Cell, 2026)

A p53-responsive microRNA-100 released from cardiomyoblasts serves as an early biomarker for acute coronary syndrome - Cheng-I Cheng; Ming-Huei Chou; Kuang-Den Chen; Po-Han Chen; Ying-Hsien Kao (Human Cell, 2026)

Potential of potentiometric biosensors for the study of ion influx and efflux via gasdermin pores in plasma membrane in pyroptosis: a hypothesis - Caglar Berkel; Oguz Özbek; Onur Cem Altunoluk (Human Cell, 2026)

HSPA8 promotes the progression of gastric cancer by activating the canonical Wnt pathway and glycolysis - Xiaoyi Shi; Peng Ge; Yalan Luo; Jianzhong Liu; Xiao Shi; Jingwen Zhang; Aixia Gong (Human Cell, 2025)

Dysfunctional variants of ABCG2 create strong individual and population risks for progression of hyperuricemia: the potential for implementation of genome-personalized nursing - Akiyoshi Nakayama; Kimiko Hayano; Miki Ueno; Yuka Miyoshi; Hiroshi Nakashima; Seiko Shimizu; Itsumi Hashimoto; Miho Toba; Rion Kikuchi; Nana Takehana; Michiru Miura; Yusuke Kawamura; et al. (Human Cell, 2025)
Gout, a common disease, develops after prolonged hyperuricemia with elevated serum uric acid (SUA) levels. Sex, overweight/obesity, heavy drinking, and aging all increase risk. Common dysfunctional variants (polymorphisms) in the ABCG2/BCRP gene are major genetic causes of gout/hyperuricemia. Early management would thus have potential benefits for public health. Several studies report the effectiveness of nurse-led care for gout management. We evaluate here the individual and population genetic effects of ABCG2 in 9244 Japanese study participants, in all of whom ABCG2 variants had a higher population-attributable fraction (PAF; approximately 30%) for progression of hyperuricemia than those for other typical environmental risk factors (overweight/obesity, heavy drinking, and aging). PAFs for aging in males and heavy drinking in females were not significant. All these factors also showed significant individual risk of increased SUA level, and ABCG2 variants had sufficient effect size to allow them to be converted into other environmental factors. To implement genome-personalized nursing, we then mapped onto the process a theoretical framework that is based on a psychological model from behavioral change theory. Because the present results for convertibility will improve the predictability of genetic effects, cognitive interventions by nurses based on individual variants could therefore encourage both inducements of behavioral change: efficacy expectations (self-efficacy) and outcome expectations. We conclude that the framework would function effectively based on cognitive interventions by nurses/paramedics. This theoretical framework has potential as a basis for implementing genome-personalized prevention, medicine and nursing of gout/hyperuricemia, and for optimizing nurse-led care.

Neuroprotective activity of thiolutin in epileptic mice: the inhibition of NLRP3 inflammasome - Jiadong Sun; Caili Fan; Xiaoyu Chen; Lei Yan (Human Cell, 2025)

Exosomal miR-145-5p impairs neoadjuvant chemotherapy by suppressing TFRC-mediated macrophage iron uptake and driving M2 polarization in esophageal cancer - Jianfeng Xu; Deng Lei; Peng Xu; Yuqi Wang; Zhupeng Li; Jiacheng Wu; Weizhong Feng; Junqing Zhou (Human Cell, 2025)

Index of human cells in *Human Cell*, 2025 - Fumio Kasai; Hiroaki Kataoka (Human Cell, 2025)

Interplay between TGF-β signaling and long non-coding RNAs in digestive system cancers: mechanisms and biological implications - Penghui Li; Di Huang; Xinyu Gu (Human Cell, 2025)
The interaction between the transforming growth factor beta (TGFβ) signaling pathway and long non-coding RNAs (lncRNAs) has been known to contribute to the progression and metastasis of digestive system cancers. Dysregulated expression of lncRNAs associated with the TGFβ-Smad signaling pathway is correlated with several clinical features in digestive system cancers. These lncRNAs regulate multiple biological functions, including epithelial-to-mesenchymal transition (EMT), tumor growth, and immune responses. They interact with key molecules in the TGFβ-Smad pathway to influence gene transcription and cellular behavior. Alterations in the expression of these lncRNAs can serve as valuable biomarkers for early detection and prognosis. Targeting the lncRNA-TGFβ axis offers a novel approach to cancer treatment. This review summarizes the interactions between the TGFβ signaling pathway and lncRNAs in digestive system cancers, highlighting their potential in diagnosis, prognosis, and therapy.

Radiotherapy or chemoradiotherapy might sensitize cervical cancer cells to plasma membrane rupture during necroptosis by upregulating the expression of SIGLEC12, a recently identified membrane-rupturing protein - Caglar Berkel (Human Cell, 2025)

Antitumoral effect of Nitraria retusa bioactive compounds on two glioblastoma cell lines - Jihed Boubaker; Aida Lahmar; Abir Salek; Mouna Selmi; Mounira kriffa; José Luis; Leila Chekir-Ghedira (Human Cell, 2025)

Generation and characterization of early stage oral cancer cell line of buccal mucosa of Indian origin - Akhila George; Sudhir Nair; Kumar Prabhash; Sayujata Thakur; Poonam Gera; Arjun Singh; Pankaj Chaturvedi; Swapnil Rane; Trupti Pradhan; Subrata Sen; Madan Barkume; Dhanlaxmi Shetty; et al. (Human Cell, 2025)
Being topmost cancer in India, oral cancer management warrants discovery of novel biomarkers, treatment strategies, and targets to help with early diagnosis, treatment, and recovery. To have a continuous supply of cells, the study was aimed at generation and characterization of established cell line from buccal mucosa (BM) tumors from patients of Indian origin which can be developed as a pre-clinical tool for biomedical application. Surgically resected tumor tissue from histo-pathologically confirmed oral cancer were processed for explant culture. TBM-02 cell line was passaged and characterized for morphology and function. Further, the cell line was silenced for inflammasome pathway gene NLRP3 to evaluate its linkage with oral cancer tumorigenesis. TBM-02, successfully established from BM, was maintained up to 100 passages, exhibited epithelioid morphology, high EpCam expression and triploid ploidy with chromosomal aberrations. Novelty and human origin of TBM-02 was authenticated by Short Tandem Repeats profiling and comparison with DSMZ database. TBM-02 revealed tumorigenic potential in vitro and in vivo which was abrogated on silencing NLRP3. Increased expression of NLRP3, hallmark of chronic inflammation in TBM-02, was validated at protein and gene level and in xenograft. TBM-02 demonstrated migratory potential and was found to be a sensitive tool to study drug response. RNA sequencing demonstrated upregulation of oral cancer-associated genes and pathways. Thus, in current study, we have reported development of novel cell line from early-stage buccal mucosa cancer patient which has a strong potential to be developed and to be used as pre-clinical model for improving oral cancer management and therapeutics. Graphical Abstract

A novel function of STARD7: its tumor-promoting role involves the activation of NF-κB signaling pathway in ovarian cancer - Tian Tian; Xiaona Luan; Lingzhi Wang; Yan Kong; Liying Huang; Yan Wang (Human Cell, 2025)

Hsa_circ_0000437 promotes the progression of rheumatic valvular heart disease by activating the mitogen-activated protein kinase signaling pathways after sponging let-7f-5p and targeting RAS-like proto-oncogene B - Linwen Zhu; Ni Li; Huoshun Shi; Jie Song; Zhongjie Fang; Qinbo Shen; Xiuying Zhu; Yanggang Dan; Guofeng Shao; Lebo Sun (Human Cell, 2025)
Circular RNAs (circRNAs) are involved in cardiovascular disease development and progression. We identified has_circ_0000437 from three pairs of clinical samples using a circRNA microarray and predicted the has_circ_0000437 sponge let-7f-5p using bioinformatics. We expanded the sample to confirm the expression, correlation, and diagnostic value of has_circ_0000437, let-7f-5p and RAS-like proto-oncogene B (RALB) in rheumatic valvular heart disease (RVHD). The effects of has_circ_0000437 and let-7f-5p on biological function were observed in hVICs cells. To explore the molecular pathogenesis of has_circ_0000437 in the RVHD process, the target binding protein RAS-like proto-oncogene B (RALB) of has_circ_0000437 was obtained using label-free mass spectrometry and parallel reaction monitoring. The influence of the has_circ_0000437/let-7f-5p/RALB axis on the expression of mitogen-activated protein kinase (MAPK)-related proteins in the inflammatory signaling pathway predicted by Kyoto Encyclopedia of Genes and Genomes (KEGG) during RVHD was measured using Western blotting. We found that let-7f-5p was at low expression and negatively correlated with has_circ_0000437, which had a diagnostic value with an area under the curve of 0.998 after the combined diagnosis. Has_circ_0000437 and let-7f-5p had binding sites, and let-7f-5p alleviated the effect of has_circ_0000437 on the proliferation, migration, and cycle progression of hVICs. The inhibitory effect of has_circ_0000437 on hVICs apoptosis was diminished. Mechanism studies showed that has_circ_0000437 promotes the MAPK pathway through has_circ_0000437/let-7f-5p/RALB axis. These findings suggest that the has_circ_0000437/let-7f-5p/RALB axis promotes the MAPK pathway, proliferation, migration, and cycle progression in RVHD, inhibiting the apoptosis process, thereby promoting RVHD development. This pathway may suggest a target for RVHD diagnosis and treatment.

Expansion characteristics of CD34+ cells derived from umbilical cord blood HS/PCs in single-parameter culture under serum-free static suspension condition - Hezhi Chen; Liying Li; Weiting Guo; Jingjing Zhu; Langyu He; Yuen Yee Cheng; Jie Xu; Yue Kang; Xiujuan Zhang; Kedong Song (Human Cell, 2025)

OTUB2 aggravates pathological cardiac hypertrophy through Rac1 activation - Junhui Xing; Lijin Lin; Yi Zhao; Zhen Shen; Yuzhen Wei; Xiaofei Xue; Fen Qin; Hengdao Liu (Human Cell, 2025)

Deciphering the relevance of dead box RNA helicases in gliomagenesis and autophagy - Arpit Sharma; Naveen Soni; Megha Chaudhary; Jingyue Jia; Bhawana Bissa (Human Cell, 2025)

Establishment of immortalized ovarian stromal cell lines using Sendai virus vectors: a platform for studying tumor–stroma interactions and carcinogenesis - Masayo Okawa; Hiroaki Komatsu; Yasuhiro Kazuki; Kanako Kazuki; Genki Hichiwa; Kohei Hikino; Yuki Iida; Mayumi Sawada; Hiroyuki Kugoh; Shinya Sato; Mitsuo Oshimura; Tasuku Harada; et al. (Human Cell, 2025)
We aimed to generate immortalized stromal cell lines from the ovarian and fallopian tube tissues of a single patient using Sendai virus (SeV) vectors and identify candidate stromal genes involved in ovarian carcinogenesis. Tissues were collected from a 48-year-old woman with endometrioid borderline tumors and endometriomas. Primary cultures were established from the right ovarian endometrioma, left ovarian surface, bilateral fallopian tube, and endometrial surface. Immortalization was achieved using SeV vectors encoding human telomerase reverse transcriptase (TERT), B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1), and Simian virus 40 large T antigen (SV40T). Morphologically, the established cells exhibited spindle-shaped fibroblast-like features and expressed stromal markers (Vimentin-positive, Keratin-negative), confirming their stromal origin. Genetic and molecular changes associated with immortalization were evaluated via chromosomal analyses, transcriptome sequencing, and reverse transcription-polymerase chain reaction (RT-PCR). SeV-infected stromal cell lines retained their proliferative capacity for over 25 passages, whereas non-infected primary cells lost their epithelial characteristics and underwent senescence after five passages. Chromosomal abnormalities were more prevalent in stromal cells derived from the ovarian endometriomas, suggesting early genomic instability. Transcriptomic profiling and RT-PCR revealed upregulation of matrix metallopeptidase 1 (MMP1), pregnancy-associated plasma protein A (PAPPA), and C-X-C motif chemokine ligand 1 in cyst-derived stromal cells compared to those from the normal ovary and fallopian tube, implicating these genes in extracellular matrix remodeling and tumor–stroma crosstalk. We established immortalized ovarian and fallopian tube stromal cell lines using SeV-based vectors. The cyst-derived stromal cells exhibited early chromosomal instability and overexpression of MMP1 and PAPPA, supporting their potential role in ovarian carcinogenesis. These immortalized stromal cell lines provide a novel and stable platform for mechanistic studies and may contribute to biomarker discovery and therapeutic target development in ovarian cancer.

CDC6 promotes the development and progression of clear cell renal cell carcinoma via upregulating RRM2 - Tianpeng Xie; Zanxuan Deng; Youping Ding; Peng Peng; Pan Rao; Yanqun Huang; Lizhen Li; Gaode Zou; Xiaofeng Zou; Mingfeng Xiang (Human Cell, 2025)

RMND5A upregulation via IGF2BP3-mediated m6A RNA modification enhances malignant traits and immune evasion in laryngeal squamous cell carcinoma cells - Shu Zhang; Xiaojun Li; Miao Zhang; Bo Kou (Human Cell, 2025)

Mitophagy is responsible to ionizing radiation but plays a very limited role in the radiosensitivity of adenocarcinoma cells - Chen Yan; Kai Huang; Yong Xu; Wei-Hang Lu; Jing Cai; Tao-Sheng Li (Human Cell, 2025)

Establishment and characterization of a novel cell line ICH-BCPALL-3 from B cell precursor acute lymphoblastic leukemia with TCF3::HLF - Keisuke Kato; Ioannis Panagopoulos; Ai Yoshimi; Norihito Ikenobe; Chie Kobayashi; Hiroaki Goto; Mieko Ito; Maiko Sagisaka; Kristin Andersen; Asami Noda; Minori Tamai; Koshi Akahane; et al. (Human Cell, 2025)

Effects of small extracellular vesicles isolated from pleural effusion on lung cancer cell proliferation and migration - G. Cammarata; A. Masucci; I. Giusti; V. Dolo; C. Di Sano; S. Taverna; E. Pace (Human Cell, 2025)
Pleural effusion (PE) is a common clinical manifestation associated with advanced stages of both malignant and non-malignant diseases. PE frequently occurs in advanced non-small cell lung cancer (NSCLC) and contributes to tumor progression. NSCLC accounts for more than 85% of the lung cancers and remains a problem worldwide due to its late diagnosis and low rate of response to treatment. Extracellular vesicles (EVs) present in PE are emerging as key mediators of intercellular communication, capable of transferring oncogenic signals through their molecular cargo. Among these molecules, microRNAs (miRNAs) are increasingly recognized as important drivers of cancer progression. miR-21 is a representative onco-miRNA, involved in lung cancer progression; moreover EV‐miR‐21 upregulation at the pre‐dissemination stage promotes cancer cell survival in the pleural cavity. This study compares, for the first time, the functional role of EVs isolated from malignant PE in NSCLC patients (NSCLC-PE-EVs) with those isolated from PE in patients with congestive heart failure (CHF-PE-EVs), focusing on their ability to modulate lung cancer cell behavior. The effects of these EVs were evaluated on COLO699 lung adenocarcinoma cells with proliferation, migration, and gene expression assays. NSCLC-PE was found to contain approximately twice the amount of EVs compared to CHF-PE. NSCLC-PE-EVs were enriched in the oncogenic miR-21-5p, while CHF-PE-EVs had higher levels of the tumor-suppressive miR-126-3p. Only NSCLC-PE-EVs induced dose-dependent increases in COLO699 cell proliferation and migration, consistent with elevated miR-21-5p expression. Functional studies confirmed that miR-21-5p mediates these effects by downregulating PTEN and PDCD4, and by upregulating MMP9 expression. Our findings show that NSCLC-PE-EVs promote malignant phenotypes in lung cancer cells via the transfer of miR-21-5p.

Establishment and characterization of a novel imatinib-resistant dermatofibrosarcoma protuberans cell line, DFSP-DPH1 - Hao Jiang; Kunqian He; Danli Li; Fengjun Zhu; Yuan Ren; Xinying Li; Yuanyuan Wang; Junbo Zhang; Yuangang Lu (Human Cell, 2025)

Interaction between gastric cancer organoids and peritoneal mesothelial cells suppresses the growth of gastric cancer organoids and induces drug resistance - Hiroyuki Uematsu; Shota Shimizu; Kunishige Onuma; Roberto Coppo; Yumi Sato; Tomoyuki Matsunaga; Yoshiyuki Fujiwara; Masahiro Inoue (Human Cell, 2025)

ONECUT2-driven activation of ADAMTS14 boosts colorectal cancer stemness via Wnt pathway - Yicheng Jiang; Xingping Tan (Human Cell, 2025)

Partial TEX14 peptides inhibit proliferation of cancer cells and have potential as anti-tumour agents - Tokuko Iwamori; Yusuke Sakurai; Tasrin Sultana; Yoshinori Katakura; Naoki Iwamori (Human Cell, 2025)

Quick and robust method for the generation of human iPSC-derived choroid plexus organoids - Rodi Kado Abdalkader; Takuya Fujita (Human Cell, 2025)

The "dual personality" of LOXL3: a tumor accomplice and a new hope for immunotherapy - Shuang Wu; Chao Huang (Human Cell, 2025)

WTAP-mediated m6A modification of PTPN1 contributes to ulcerative colitis pathogenesis through regulating colonic epithelial cell phenotypes - Yichi Zhang; Nijina Li; Dan Zhang; Hao Zhang (Human Cell, 2025)

Screening and validation of autophagy-related mRNAs and lncRNAs in bone nonunion based on transcriptome sequencing analysis - Wei Xu; Qianliang Wang; Meng Li; Feng Tian; Lei Liu; Jun Yan (Human Cell, 2025)

Srpx2 exerts multifaceted cardio-protection in septic cardiomyopathy: PI3K/AKT-dependent attenuation of mitochondrial oxidative stress, apoptotic signaling, and inflammatory response - Yan Guo; Ying Liu; Mingkai Zhou; Yulan Zhao (Human Cell, 2025)

SerpinB1 reduces neutrophil airway inflammation, airway remodeling, and pyroptosis in asthmatic mice by interacting with Elane - Na Chen; Zhu Chen; LianKe Li; Zhiwei Liu; Qiong Tao; Weizhou Wang; Yang Yang (Human Cell, 2025)

TPM3–NTRK1 fusion confers resistance to osimertinib in lung adenocarcinoma: a model in a continuous cell line - Fang Cao; Jiayin Dai; Kun Dong; Zhenli Yang; Yanli Zhu; Changsong Qi; Dongmei Lin; Xiaocui Bian; Yuqin Liu (Human Cell, 2025)

The likely role of hydrogen sulfide-mediated regulation of pyroptosis in polycystic ovaries - Caglar Berkel (Human Cell, 2025)

Overexpression of miR-454-3p inhibits high glucose-induced ET-1 expression, leading to eNOS upregulation in endothelial cells: an integrated bioinformatics and experimental analysis - Weifang Li; Qiuwang Zhang; Michael J. B. Kutryk (Human Cell, 2025)

Psoriasis and lichen planus: an immunohistochemical study of Trophoblast cell-surface antigen 2 expression in skin biopsies - Giovanni Tossetta; Sonia Fantone; Alessandra Filosa; Carlo Francesco Tomasini; Paola Savoia; Daniela Marzioni (Human Cell, 2025)

Long non-coding RNA FEZF1-AS1 suppresses ferroptosis in multiple myeloma cells through KIAA1429-mediated m6A modification - Qing Su; Weiliang Liu; Peijin Wang; Mingyi Wang (Human Cell, 2025)

Cedrol impedes lung cancer metastasis by reducing tumor-associated macrophage polarization mediated by MYC-driven aerobic glycolysis - Qingsheng Li; Yuxi Liu; Lin Zhang; Yi Zheng; Xiaofan Feng; Yanjie Wang (Human Cell, 2025)

Multifaceted roles of microbiota-derived deoxycholic acid in gastrointestinal cancers: from barrier disruption to therapeutic implications - Hai Zhao; Fan Yang; Jiaxin Yang; Sheng Yang (Human Cell, 2025)

Establishment of human histiocytic sarcoma organoids dependent on the SHH/YAP pathway - Yusuke Yoshimura; Keiichi Yoshida; Yukiko Matsuoka; Satoru Sasagawa; Noriko Nagamine; Yoji Kukita; Ryota Miyamoto; Rie Suzuki; Hironari Tamiya; Shigeki Kakunaga; Toshinari Yagi; Takuya Terakawa; et al. (Human Cell, 2025)

Single-cell transcriptome analysis highlights a critical role of ATG5 for endothelial cells in diabetic nephropathy - Yun Zhang; Lishuang Che; Hanyuan Gao; Quanzuan Zeng; Jiequn Zhang; Yanling Zheng; Yuangen Li; Xiaoqing Chen (Human Cell, 2025)

Multi-omic analysis constructs ferroptosis subtypes and risk signature and reveals that PEBP1 is an important tumor suppressor in kidney cancer - Shuaiqi Chen; Xizi Cheng; Zeyu Li; Huijun Fan; Xiangdong Xue; Kuo Ma; Jingxian Li; Feng Zhu (Human Cell, 2025)

Emerging role of the E3 ubiquitin ligase RNF114 in health and disease - Qian Wang; Shihan Cao; Zhenzhen Sun; Zhanjun Jia; Shiwei Yang (Human Cell, 2025)

Elucidating the risk factors and oncogene drivers of acute myeloid leukemia - Daniel Ruben Akiola Sanya; Djamila Onésime (Human Cell, 2025)

ZWINT down-regulated by miR-495-3p inhibited lung metastasis of breast cancer by blocking p38 MAPK signaling pathway activation - Ming-tao Shao; Wei-wen Li; Yong Li; Ping Chen; Shuai-shuai Yu; Wen-jie Lu; Chun-mei Chen; Yan Dong; Yi-wen Zhang; Qun-chen Zhang (Human Cell, 2025)
Breast cancer metastasis is the primary cause of patient mortality, yet effective therapeutic targets remain limited. Building on our prior identification of ZWINT as a prognostic marker linked to metastasis, this study defines its critical functional role and regulatory mechanism. Multi-omics analysis revealed a strong association between ZWINT expression and metastatic processes across breast cancer subtypes. Functionally, ZWINT knockdown significantly inhibited breast cancer cell migration and invasion in vitro and dramatically reduced lung metastasis in vivo. Mechanistically, we discovered that miR-495-3p directly targets and suppresses ZWINT expression, and this miR-495-3p/ZWINT axis acts through inhibiting p38 MAPK pathway activation to suppress metastatic progression in vitro. Our findings demonstrate that ZWINT drives breast cancer metastasis and is negatively regulated by miR-495-3p. The newly identified miR-495-3p/ZWINT/p38 MAPK axis may provide a promising therapeutic target for suppressing breast cancer progression.

Podocytes in health and disease: from development to regeneration - Yusuke Nishimura (Human Cell, 2025)

METTL14 knockdown augmented the polarization of M2-like macrophages to promote acute myeloid leukemia progression - Meng Wang; Zhibin Xie; Yuanyuan Tan; Yan Zhou; Siyi Wang; Pingping Zhang; Jiajia Li (Human Cell, 2025)

Hofbauer cell alterations and potential role in the pathophysiology of HELLP syndrome - Ayano Ezaki; Akihito Sagara; Yoshihiro Komohara; Cheng Pan; Hiromu Yano; Shukang Zhao; Mayuko Yamamoto; Anri Imamura; Hinano Akita; Jie Su; Ren Shirotani; Tomoka Takahashi; et al. (Human Cell, 2025)

Eucommia ulmoides (Duzhong) extract alleviates cerebral stroke by inhibiting ferroptosis-related gene DNA Damage-Inducible Transcript 4 (DDIT4) expression - Xin Qi; Mengyuan Deng; Minhong Li; Wenjia Ma; Yangbo Zhou (Human Cell, 2025)

Exportin-1 and epigenetic modifications interaction: more than nuclear transport - Leonidas Benetatos; Eleftheria Hatzimichael; Eleni Kapsali (Human Cell, 2025)

Generation of human induced pluripotent stem cell lines derived from Wolf–Hirschhorn syndrome patients with chromosomal 4p deletion - Tomoya Shimizu; Miho Takami; Mami Matsuo-Takasaki; Michiya Noguchi; Yukio Nakamura; Tadayoshi Hayata; Yohei Hayashi (Human Cell, 2025)
Wolf–Hirschhorn syndrome (WHS) is a devastating congenital disease caused by deletions on the short arm of chromosome 4 (4p), for which no curative treatments currently exist. To facilitate the development of therapeutic strategies, the development of experimental models of WHS is crucial for investigating its etiology and pathogenesis, which remain elusive. In this study, we successfully generated human induced pluripotent stem cells (hiPSCs) from three fibroblast lines from WHS patients. We then characterized these hiPSCs, along with one hiPSC line previously generated from peripheral blood mononuclear cells, as part of a Japanese nationwide project. All four hiPSC lines exhibited characteristics of self-renewal, pluripotency, and karyotypes with expected 4p deletions. Copy number variation microarray analysis revealed that these WHS-specific hiPSCs carried hemizygous deletions in p15.1–p16.3 regions, commonly encompassing 100 genes. Transcriptome analysis showed that the expression of these genes faithfully reflected hemizygous deletion in these WHS-specific hiPSCs and that these down-regulated genes were associated with the development of neural crest cells. These results indicate that WHS-specific hiPSCs can recapitulate the abnormal genomic structure genes related to and the gene expression profile observed in WHS patients. Given the limited understanding of the molecular pathogenesis of WHS, these cellular resources will be instrumental in modeling disease phenotypes and in advancing novel therapies for this syndrome.

ODC1 loss upon KLF6 upregulation promotes macrophage pyroptosis and acute kidney injury in sepsis - Jiansheng Ding; Shijie Zhang; Xiangxian Zhang (Human Cell, 2025)

tRNA-derived small RNAs: emerging regulators of ferroptosis in human diseases - Jiqing Zhang; Mu Liu; Zhongjun Li (Human Cell, 2025)

A stem cell-based toolkit to model Angelman syndrome caused by paternal uniparental disomy of chromosome 15 - Francisca Cazaux Mateus; João Camões dos Santos; Maria Arez; Evguenia P. Bekman; Simão T. da Rocha (Human Cell, 2025)
Angelman syndrome is a rare neurodevelopmental disorder caused by the loss of function of the maternally inherited UBE3A gene within the chr15q11-q13 region. This gene is subjected to a tissue-specific form of genomic imprinting leading to the silencing of the paternal allele in neurons. Angelman syndrome can result from various (epi)genetic mechanisms, with paternal uniparental disomy of chromosome 15 (patUPD15) being one of the rarest and least studied due to the absence of suitable models. To address this gap, we generated three independent induced pluripotent stem cell (iPSC) lines from individuals with Angelman syndrome caused by patUPD15, alongside genetically matched unaffected familial controls. Peripheral blood mononuclear cells (PBMCs) were reprogrammed into iPSCs using a non-integrative Sendai virus-based approach expressing the Yamanaka factors. All iPSC lines underwent rigorous quality control, confirming stem cell identity, trilineage differentiation potential, and genetic and epigenetic integrity. This newly established iPSC toolkit provides a powerful platform to investigate the molecular underpinnings of Angelman syndrome caused by patUPD15, paving the way for future translational research and therapeutic development tailored for this understudied form of the disorder.

Melatonin, ROR-α and circadian rhythm in liver - Samanmitha Srinivasa; Shuchi Odiyanda Charmanna; Rachana Rajesh Nayak; Shreyas Hulusemane Karunakara; Prasanna Kumar Santhekadur (Human Cell, 2025)

Establishment of KGAS, a cell line derived from gastric-type adenocarcinoma of the uterine cervix - Hiroaki Yamada; Akira Yokoi; Eri Asano-Inami; Masami Kitagawa; Kosuke Yoshida; Kazuhiro Suzuki; Shin Nishio; Hiroaki Kajiyama; Naotake Tsuda (Human Cell, 2025)
Gastric-type adenocarcinoma (GAS) of the uterine cervix is a rare and aggressive subtype of cervical adenocarcinoma characterized by intrinsic resistance to chemotherapy and poor clinical outcomes due to the lack of effective treatment options. To address this critical unmet need, we established a novel GAS-derived cell line, KGAS, from ascitic fluid collected from a patient with recurrent GAS. Short tandem repeat (STR) analysis confirmed the genetic identity between the primary tumor and the cell line. Upon transplantation into immunocompromised mice, KGAS cells formed tumors that expressed Claudin-18 and MUC6, clinically recognized markers of GAS. Furthermore, KGAS cells exhibited marked resistance to paclitaxel and carboplatin, showing significantly reduced growth inhibition compared to HeLa cells. We also established a paclitaxel- and carboplatin-resistant subline, rKGAS, and performed microRNA (miRNA) sequencing to explore the molecular basis of acquired chemoresistance. Seventeen differentially expressed miRNAs were identified between KGAS and rKGAS cells. Upregulated miRNAs in rKGAS were predicted to target oncogenes such as BCL2, MET, SIRT1, and VEGFA, whereas downregulated miRNAs were associated with tumor suppressor genes, including IGF1R, TNFAIP3, and MTOR. The KGAS and rKGAS cell lines represent valuable preclinical models for elucidating the molecular mechanisms of chemoresistance and malignant progression in cervical GAS, and may contribute to the development of novel therapeutic strategies for this challenging cancer subtype.

The SWI/SNF chromatin remodeling complex subunit BAF53B as an immunohistochemical marker for neuroendocrine neoplasms - Kouhei Sakurai; Mako Ochiai; Kanata Kojima; Kento Kato; Tatsuya Ando; Taku Kato; Hiroyasu Ito (Human Cell, 2025)

Apigenin inhibits endothelial-to-mesenchymal transition of coronary artery endothelial cells and myocardial fibrosis by regulating ribosome biogenesis through GTPBP4 modulation - Xiaoyong Hu; Zhaoying Yang; Rui Tang; Zhongying Lv; Ting Zou; Yuanyuan Dou; Hongjian Li (Human Cell, 2025)

Correction: Long non-coding RNA DUXAP10 exerts oncogenic properties in osteosarcoma by recruiting HuR to enhance SOX18 mRNA stability - Guantong Wang; Qian Zhang; Qinjue Wang; Jing Wang; Lulu Chen; Qiang Sun; Dengshun Miao (Human Cell, 2025)

SIRT1 as a potential target for age-related eye diseases: mechanisms and therapeutic strategies - Huirui Liu; Yuting Ouyang; Hongyan Ge (Human Cell, 2025)

USF1-induced RPS6KB2 activation influences aggressive phenotype in B-cell non-Hodgkin lymphoma - Zhaoyu Liu; Xiang Song; Zhuang Liu; Xiaoyu He; Hong Gao; Xunru Liu (Human Cell, 2025)

100% Fish oil-based lipid emulsion inhibits hepatic stellate cell activation via suppression of the TGF-β1 autocrine signaling - Ryo Watanabe; Mayako Morii; Kenki Yamagata; Takashi Ebihara; Takehiko Sasaki; Yoshihiro Mezaki; Masaru Mizuno (Human Cell, 2025)

FTO inhibited miR-487a-3p biosynthesis via N6-methyladenosine-dependent pathway to promote WNT5A-mediated osteogenic differentiation of adipose-derived stem cells - Yong Li; Yang Yue; Chaoqun Cen; Bo Liu (Human Cell, 2025)

Nicotinamide N-methyltransferase enhances paclitaxel resistance in ovarian clear cell carcinoma - Ryoko Kikuchi-Koike; Masaru Sakamoto; Yuko Sasajima; Yuko Miyagawa; Hiroshi Uozaki; Kenji Umayahara; Kei Hashimoto; Yuko Takahashi; Kazuki Takasaki; Chikara Kihira; Haruka Nishida; Takayuki Ichinose; et al. (Human Cell, 2025)
Nicotinamide N-methyltransferase (NNMT) is an S-adenosyl-l-methionine (SAM)-dependent cytosolic enzyme, and a growing body of evidence suggest that it plays an essential role in cancer progression. Recently, NNMT has a role in methylation metabolism and tumorigenesis and was associated with a poor prognosis against numerous cancers. In addition, it has been reported that NNMT has been overexpressed in the stroma of advanced high-grade serous carcinoma and may contribute to decreased survival. This study aimed to identify novel biomarkers to predict resistance and investigate their clinicopathologic significance in paclitaxel-resistant advanced or recurrent ovarian clear cell carcinoma (OCCC). Fluorescence-labeled two-dimensional differential gel electrophoresis (2D-DIGE), immunohistochemical, and MASCOT analyses allowed us to identify the cytoplasmic metabolic enzyme NNMT. In cultured cell studies, NNMT protein expression was higher in paclitaxel-resistant OVMANA and OVTOKO cells than in paclitaxel-sensitive KK and ES-2 cells. Furthermore, although analysis of clinical tissue samples showed no association with poor prognosis in 7 individuals with low NNMT expression in the cytoplasm of OCCC cells, high expression of NNMT in the cytoplasm of OCCC cells may be associated with low sensitivity to paclitaxel in OCCC and may have prognostic implications. Therefore, targeting therapy to reduce cytoplasmic NNMT expression levels may increase the sensitivity of OCCC to paclitaxel.

Regulatory T cells in cancer anti-PD-(L)1 therapy - Keywan Mortezaee (Human Cell, 2025)

Simulating tumor complexity: 3D pancreatic tumor spheroid model for improved drug screening - Bano Subia; Ankit Patel; Simran Nathwani; Krishnarup Ghoshdastidar; Mukul Jain; Kasinath Viswanathan (Human Cell, 2025)

Collagen alpha-5(IV) chain activation by nuclear factor 1/C promotes nasopharyngeal carcinoma progression - Ying Cao; Peibei Wang; Peng Li; Kai Wei; Xinle Kang; Xiao Han; De Huai; Bing Fei (Human Cell, 2025)

The cell-surface serine protease prostasin is lost during cervical squamous cell carcinogenesis - Joseph G. Lundgren; Michael G. Flynn; Karin List (Human Cell, 2025)

The expression of PD-1 ligands in the immune microenvironment was altered in TTF-1-negative lung adenocarcinoma - Hiroyuki Yamada; Hiromu Yano; Eri Matsubara; Shukang Zhao; Yusuke Shinchi; Cheng Pan; Takamasa Koga; Kosuke Fujino; Yukio Fujiwara; Koei Ikeda; Yoshihiro Komohara; Makoto Suzuki (Human Cell, 2025)
Thyroid transcription factor-1 (TTF-1) is a lineage-specific marker for lung adenocarcinoma (LUAD), whereas the relatively minor subset of TTF-1-negative LUADs shows a poor prognosis and a limited response to therapy. However, its relationship with the tumor immune microenvironment remains poorly defined. How TTF-1 expression affects the immune context in LUAD was investigated, focusing on tumor-associated macrophages (TAMs) and T-cell infiltration. Immunohistochemical (IHC) analysis of 226 LUAD specimens showed that TTF-1-negative tumors were associated with epidermal growth factor receptor wild-type status, advanced stage, and worse progression-free and cancer-specific survivals. Notably, PD-L1 (programmed death-ligand 1) and PD-L2 expression in TAMs, but not in cancer cells, was significantly reduced in TTF-1-negative tumors. Public single-cell RNA sequencing data confirmed downregulation of CD274 (PD-L1) in TAMs from tumors with low expression of TTF-1-related genes. In contrast, PDCD1LG2 (PD-L2) expression showed less consistent patterns. On IHC analysis, infiltration of CD8 + and CD4 + T cells was modestly lower in TTF-1-negative tumors, accompanied by decreased HLA class I and II expressions. Transcriptomic analysis of The Cancer Genome Atlas LUAD cohort further showed lower interferon gamma (IFN-γ) signaling and decreased T cell-inflamed gene signatures in the low TTF-1-negative tumors. These findings suggest that TTF-1-negative LUAD exhibits more immune-suppressive features, with a relatively reduced antitumor immune response characterized by decreased T-cell infiltration and INF-γ signaling, which are related to PD-L1 and PD-L2 expressions in TAMs.

Exosomal FGD5-AS1 promotes proliferation of lung cancer cells under hypoxia by inhibiting miR-1179 and activating P-cadherin - Bilan Yang; Zhongkun Tian; Zhiqiang Luo; Yi Yuan; Qiang Wen; Zhihua Liu (Human Cell, 2025)

Establishment and characterization of a new Chinese extrahepatic cholangiocarcinoma cell line, EBC-X1 - Yuanhui Su; Huan Tang; Xin Miao; Cheng Yu; Changpeng Chai; Wei Huang; Lu Li; Jieyu Zheng; Tao Xu; Fa Jin; Zhipeng Ye; Zhao Hu; et al. (Human Cell, 2025)

Unveiling the vital role of OGG1 in inflammation, vascular endothelial damage, and cell death in obstetric and gynecological diseases - Yang Li; Wenying Zhang; Bo Wang; Fuju Wu (Human Cell, 2025)
The DNA repair enzyme 8-oxoguanine DNA glycosylase-1 (OGG1) plays a crucial role in the initiation of DNA base excision repair pathway by recognizing and excising the oxidative base lesions including 7,8-dihydro-8-oxoguanine (8-oxoG). Beyond its canonical function in DNA repair, OGG1 has been implicated in regulating inflammation-related genes, growth factor expression, and various cell death pathways, including apoptosis, parthanatos, and autophagy. These mechanisms are often involved in obstetric and gynecological disorders, which are frequently characterized by inflammation, endothelial dysfunction, and dysregulated cell death. As such, OGG1 emerges as a potential therapeutic target for these conditions. However, comprehensive reviews detailing OGG1’s mechanistic roles in reproductive diseases remain scarce. This review aims to synthesize current knowledge primarily on non-canonical functions of OGG1, with a focus on its potential involvement in disorders such as endometriosis, polycystic ovary syndrome, uterine fibroids, and malignancies, and to highlight its promise as a therapeutic target.

ATG5-mediated cGAS-STING-NLRP3 axis alleviates symptoms of knee osteoarthritis - Hao Wu; Jinhong Yan; Qian Zhang; Gong Cheng; Zhilin Cao (Human Cell, 2025)

Bone marrow mesenchymal stem cell-derived exosomal METTL14 promotes the osteogenic differentiation of MC3T3-E1 cells by regulating BMP2 in bone fracture recovery - Min Liu; Zhenye Guo; Xiaoyan Shi; Zhengquan Dong; Huyun Qiao; Dong Wang; Yonghong Zhang (Human Cell, 2025)

Robo4 inhibits neovascularization in oxygen-induced retinopathy by regulating ARF6 and VEGF - Yujun Liao; Chunhong Yu; Weiwei Xiong; Xiaolong Yin (Human Cell, 2025)

Leucyl-tRNA synthetase promotes malignant progression in diffuse large B-cell lymphoma by regulating glycolysis via the LRPPRC/HIF-1α/HK2 axis - Weiming Zhang; Nasha Yu; Xiangxiang Song; Xing Zhong (Human Cell, 2025)
Diffuse large B-cell lymphoma (DLBCL) is a malignant tumor and research on its therapeutic targets has received increasing attention. It has been reported that Leucyl-tRNA synthetase (LARS) contributes to the growth and migration of non-Hodgkin lymphoma (NHL), yet its effect on DLBCL progression remains to be elucidated. MTT and flow cytometry were carried out to determine the cellular phenotypes of DLBCL cells under LARS overexpression. The differentially expressed proteins (DEPs) were screened by mass spectrometry. ELISA, western blot, and xenograft tumor experiments were implemented to confirm the impact of LARS and the LRPPRC/HIF-1α axis on malignant progression and glycolysis. Dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) were applied for exploring the underlying mechanism by which LARS was regulated. LARS promoted the malignant phenotypes, such as increasing cell proliferation and inhibiting apoptosis, and enhanced abnormal glycolysis both in vitro and in vivo. Based on mass spectrometry and functional recovery experiments, we found that LARS upregulated LRPPRC expression. More importantly, overexpressing LRPPRC facilitated malignant phenotypes and glycolysis through the elevation of HIF-1α expression, which could be reversed by silenced HIF-1α. Mechanistically, LARS promoted the expression of HIF-1α by activating LRPPRC, which in turn enhanced the transcription of HK2, thereby facilitating malignant progression and abnormal glycolysis. LARS facilitated abnormal glycolysis via the LRPPRC/HIF-1α/HK2 axis, thereby promoting the malignant progression of DLBCL.

Palmatine inhibits colorectal cancer proliferation and metastasis by regulating miR-363-3p/AURKA axis - Changxia Mao; Xue Chai; Huan He; Jianyu Zhu; Juan Li; Hang Ma; Xuegang Li; Xiaoli Ye (Human Cell, 2025)

Establishment of Coala: a novel 3D and 2D cancer cell line derived from colorectal cancer liver metastasis - Sandra Mersakova; Juraj Marcinek; Dusan Brany; Olga Chodelkova; Martin Vorcak; Martin Cermak; Martina Poturnajova; Zuzana Kozovska; Henrieta Skovierova; Slavomira Novakova; Barbora Mitruskova; Dusan Loderer; et al. (Human Cell, 2025)
Metastatic colorectal cancer is one of the most critical causes of cancer-related dead in patients suffering this type of malignancy. As the liver metastases are found in almost 25–50% of all colorectal cancer patients, there is an urgent need for suitable in vitro and in vivo models. To the best of our knowledge, only a limited number of well-described 2D or 3D organoid/spheroid cell lines originated from human liver metastases was reported for this type of malignancy and submitted to ATCC and other repository centers for general use. Here, we present a novel, well-characterized cell line Coala that was derived directly from liver metastasis of patient with colorectal cancer. Coala cancer cell line was derived by 2D and 3D culture technology and can be, therefore, cultured as standard 2D cell line or as 3D spheroid culture. When transplanted into athymic mice, Coala cell line forms fast growing tumors with histological features similar to original tumor and expressed CDX2, SATB2, and CK20 . Whole exome sequencing analysis of Coala cell line showed the presence of pathogenic mutations in C8B , PRKCQ , IRGM , FGFR4 , POLR1C , APC and TP53 genes. As verified by antibody array chip analysis, Coala cells express Snail , Pdx-1 , FoxA2, and E-cadherin . Our cell line represents a new, well characterized in vitro research tool for cancer research and will be available to researchers in the field via biorepository centers.

Activated PLK1 promotes the migration and invasion of polyploid giant cancer cells with daughter cells via β-catenin/STAT3 signaling pathway - Xinyue Zhou; Yidi Ning; Xiaorui Wang; Jing Xu; Yandi Liu; Mingqing Zhang; Shiwu Zhang (Human Cell, 2025)

Establishment and characterization of a novel patient-derived TP63-rearranged anaplastic large-cell lymphoma model PTCL-S1 - Kelila Xin Ye Chai; Elizabeth Chun Yong Lee; Zhimei Li; Nur Ayuni Binte Muhammad; Jing Quan Lim; Dachuan Huang; Soon Thye Lim; Jason Yongsheng Chan; Choon Kiat Ong (Human Cell, 2025)
Anaplastic large-cell lymphoma (ALCL) accounts for 15% of all peripheral T-cell lymphomas globally and can be further divided into subcategories, of which patients with ALK-negative ALCL have dismal prognosis and overall survival. We established a patient-derived xenograft (PDX) and in vitro model (designated PTCL-S1) of TP63 -rearranged ALK-negative ALCL from the primary tumour site of a 55-year old Chinese woman. Whole genome sequencing of the patient’s tumour identified various mutations including AKT1 and NOTCH1 , as well as the TP63 - TBL1XR1 gene fusion. RNA sequencing followed by Sanger sequencing confirmed the gene rearrangement in original tumour, PDX and PTCL-S1 cell line. Immunohistochemistry profiling of the PDX model and cell-line were consistent with the patient’s primary tumour sample (CD3 + /CD30 + /CD79a-). Cytotoxic agents (doxorubicin, etoposide and gemcitabine) commonly used in ALCL treatment exhibited potent anti-proliferative activity in the cell-line. In conclusion, the established PTCL-S1 cell line can be a useful tool for further investigation of the understanding of TP63 -rearranged ALK-negative ALCL.

Editorial Expression of Concern: Human placental mesenchymal stromal cell therapy restores the cytokine efflux and insulin signaling in the skeletal muscle of obesity-induced type 2 diabetes rat model - Nagasuryaprasad Kotikalapudi; Samuel Joshua Pragasam Sampath; Sukesh Narayan Sinha; R. Bhonde; Sathish Kumar Mungamuri; Vijayalakshmi Venkatesan (Human Cell, 2025)

Correction: IL-32/NFκB/miR-205 loop sustains the high expression of IL-32 and enhances the motility of cervical cancer cells - Jianbing Liu; Kai Yang; Xiaoyu Lin; Jing Xu; Xiaohua Cui; Jianqing Hao; Wei Wang; Wenhao Wang; Li Li; Min Hao (Human Cell, 2025)

SMU-pRMS: a novel cell line of pleomorphic rhabdomyosarcoma - Naoya Nakahashi; Makoto Emori; Yasutaka Murahashi; Kazuyuki Murase; Junya Shimizu; Kenji Murata; Tomohide Tsukahara; Shintaro Sugita; Kousuke Iba; Kohichi Takada; Makoto Osanai; Atsushi Teramoto (Human Cell, 2025)

Blocking secretion of exosomes by GW4869 dampens CD8+ T cell exhaustion and prostate cancer progression - Jing Liu; Hongyan Guo; Shiqi Liu; Yinying Hu; Yanqin Huang; Jiping Rong; Fang Yuan; Ruping Wang; Zhigang Wang (Human Cell, 2025)
Functional exhaustion of T lymphocytes is considered an important factor in the failure of tumor treatment. Accumulating evidence has shown that tumor cells cultivate their immune microenvironment through secreting exosomes. However, the mechanism through which tumor cell-derived exosomes participate in the regulation of lymphocyte function remains unclear. In this study, we found that exosomes derived from prostate cancer (PCa) cells were able to upregulate the expression of PD-1 and TIM-3 in CD8 + T cells, inducing the secretion of cytokines related to T cell exhaustion and significantly decreasing the ability to kill PCa cells. Importantly, our data indicated that treatment with GW4869 could reverse the effects of PCa-derived exosomes on CD8 + T cells and further inhibit the growth of PCa cells in vivo and in vitro by blocking the generation of exosomes. Our findings support the notion that exosomes derived from PCa cells can induce T cell exhaustion and promote PCa progression, while treatment of GW4869 effectively rejuvenates CD8 + T cells and reverses the effect of PCa exosomes. These findings indicate that GW4869 has potential in the treatment of PCa.

Metformin promotes osteogenic differentiation of human periodontal ligament stem cells via KLF2-mediated activation of miR-181a-5p under lipopolysaccharide stimulation - Xu Zhang; Wen Hu; Hua Hua (Human Cell, 2025)
Periodontal ligament stem cells (PDLSCs) constitute a promising source for successful periodontal regeneration. This study aims to explore roles of metformin, krüppel-like factor 2 (KLF2), and miR-181a-5p in mediating osteogenic differentiation of human PDLSCs (hPDLSCs) following lipopolysaccharide (LPS) stimulation. The osteogenic differentiation potential of hPDLSCs isolated from human premolar root samples were examined by alkaline phosphatase (ALP) staining, ALP activity assay, Alizarin red S staining, and Western blotting of osteogenic markers. Metformin pretreatment at dose of 100 μM significantly resulted in increased ALP activity, elevated protein expressions of osteogenic markers, and more generated mineralized matrix in hPDLSCs with LPS stimulation. KLF2 and miR-181a-5p were found to be increased by metformin pretreatment at dose of 100 μM in hPDLSCs with stimulation but not in hPDLSCs without LPS stimulation. The interaction between the KLF2 and the promoter of miR-181a-5p was noted by the dual-luciferase reporter assay. KLF2 knockdown or miR-181a-5p inhibition notably abrogated the improvements of osteogenic differentiation by metformin pretreatment in LPS-stimulated hPDLSCs. The findings of the study indicate metformin protects hPDLSCs against impaired osteogenic differentiation of hPDLSCs after LPS stimulation by KLF2-mediated activation of miR-181a-5p under inflammation conditions.

Activation of the circAGFG1/miR-195-5p/PD-L1 axis induces lung injury in sepsis - Yang Bi; Rui Ding; Xinyan Liu; Yun He; Xukun Liu; Shouye Ma; Chaofan Wang; Zhongfa Zhang; Xuan Song (Human Cell, 2025)
Severe sepsis can escalate to acute lung injury (ALI), a critical condition with limited treatment options. Emerging research highlights the role of non-coding RNAs, including microRNAs (miRNAs) and circular RNAs (circRNAs), in regulating epithelial and immune cell responses in sepsis-induced ALI. This study delves into the circAGFG1/miR-195-5p/PD-L1 axis to elucidate its potential in this context. The conducted experiments using Th17 cells differentiated from CD4+ T cells isolated from human umbilical cord blood, co-cultured with transfected Calu-3 cells. The assessed cell viability, RNA, and protein expression levels under inflammatory stimuli. In addition, we collected bronchoalveolar lavage fluid and lung tissues from a cecal ligation and puncture mouse model. Quantification of RNA and protein expression of inflammatory and survival markers provided insights into the regulatory mechanisms involved. Peripheral blood samples from sepsis/ALI patients and healthy controls revealed that circAGFG1 expression is significantly downregulated, while miR-195-5p expression is upregulated in patients compared to healthy individuals. In both Calu-3 cells and induced Th17 cells, as well as in sepsis-induced ALI mouse models, the circAGFG1/miR-195-5p/PD-L1 axis was shown to regulate the expression of inflammatory cytokines, Th17 cell differentiation, and markers of epithelial cell survival. Results show the circAGFG1/miR-195-5p/PD-L1 axis plays a critical role in the pathogenesis of sepsis-induced ALI. Targeting this axis could present a novel therapeutic strategy for preventing ALI in sepsis and other conditions characterized by heightened lung inflammation. This research paves the way for new treatment approaches, offering hope for improved outcomes in patients suffering from severe sepsis and ALI. Graphical abstract

Establishment and characterization of two novel patient-derived cell lines from giant cell tumor of bone: NCC-GCTB11-C1 and NCC-GCTB12-C1 - Yuki Adachi; Takuya Ono; Rei Noguchi; Julia Osaki; Shuhei Iwata; Taro Akiyama; Kazuyoshi Yanagihara; Shogo Nishino; Koichi Ogura; Akihiko Yoshida; Hideki Yokoo; Akira Kawai; et al. (Human Cell, 2025)

Senescence of dental pulp stem cells: phenotypes, underlying mechanisms and regulatory molecules - Ping Zhang; Yu Cui; Zekun Li; Luyun Liu; Xinjuan Liu; Xiaoling Ding; Gang Ding (Human Cell, 2025)

Multi-epitope vaccines: charting a new frontier in monkeypox prevention and control - Pooja Tiwary; Krishil Oswal; Ryan Varghese; Harsh Anchan; Mitul Oswal (Human Cell, 2025)

Establishment and characterization of preclinical model of primary ovarian squamous cell carcinoma - Chenyang Xu; Weiming Xu; Conghui Wu; Chen Xu; Zhengxiao Ma; Jiamin Wang; Yue Zhuo; Xinan Cai; Yuting Zhang; Yingqi Lyu; Jinchao Wang; Minran Huang; et al. (Human Cell, 2025)

Exosomes derived from human umbilical cord mesenchymal stem cells inhibit hepatocyte pyroptosis via miR-423-5p/ZBP1 in acute liver failure - Dan Xie; Lina Yu; Ziyang Wang; Gongqin Qiu; Shi Ouyang (Human Cell, 2025)
Human umbilical cord mesenchymal stromal cells (hucMSCs) have emerged as a promising therapeutic option for acute liver failure (ALF). However, the detailed mechanism by which hucMSCs modulate hepatocyte pyroptosis in ALF remains unclear. In this study, we induced ALF in mice using acetaminophen (APAP). Mice were intravenously injected with 1 × 10 6 hucMSCs/ hucMSCs-Exo via the tail vein 6 h after APAP administration. Liver pathological changes were assessed by hematoxylin and eosin (H&E) staining. Subsequently, an in vitro model of liver cell failure and pyroptosis model was established using LO2 cells treated with lipopolysaccharide (LPS) and adenosine 5’-triphosphate (ATP). The levels of cell pyroptosis marker caspase-1 were detected by flow cytometry analysis, RT-qPCR assay, and western blot assay. The study employed a comprehensive approach, including flow cytometry analysis, RT-qPCR assay, miRNA sequencing, and luciferase reporter gene experiments. hucMSCs and hucMSCs- exosomes (MSCs-Exo) inhibited cell inflammation to improve ALF in vivo model of ALF and inhibited hepatocyte pyroptosis in LO2 cells induced by ATP and LPS. MiR-423-5p emerged as a potential mediator of the anti-pyroptotic effects of hucMSCs-Exo, with ZBP1 identified as one of its downstream targets. Subsequent validation confirmed that miR-423-5p targets ZBP1 to regulate pyroptosis. These findings highlight the role of hucMSCs-derived exosomal miR-423-5p in inhibiting hepatocyte pyroptosis in LO2 cells induced by ATP and LPS. miR-423-5p serves as a crucial mediator in this process, targeting ZBP1, a protein significantly involved in the pyroptotic pathway. Our findings may provide basics for further research on mechanism of hucMSCs and present a promising cell-free strategy treating ALF.

CircTADA2A inhibits cell proliferation and promotes ferroptosis by sponging miR-638 in acute myeloid leukemia - Yuan Yuan; Jiajia Li; Meng Wang; Yan Jin; Ruixiang Xia (Human Cell, 2025)

Establishment and characterization of NCC-EMC1-C1: a novel patient-derived cell line of extraskeletal myxoid chondrosarcoma - Shuhei Iwata; Rei Noguchi; Julia Osaki; Yuki Adachi; Yomogi Shiota; Shuhei Osaki; Shogo Nishino; Akihiko Yoshida; Seiji Ohtori; Akira Kawai; Tadashi Kondo (Human Cell, 2025)

Generation of human-induced pluripotent stem cells from a patient with Beckwith–Wiedemann syndrome - Mei Tang; Jiafan Lei; Congwen Shao; Wenyan Zhou; Min Xiong; Min Huang; Chunyan Huang; Fei Wang; Jun Liu; Jun Li; Xueqing Xu (Human Cell, 2025)

Identification of autophagy-related biomarkers in prostate cancer prognosis - Yancheng Di; Linlin Zhao; Lingling Zhang; Lei Chen (Human Cell, 2025)

EZH2 regulates tumor-associated macrophages by the KDM6A-mediated inflammatory response in HPV16-positive cervical cancer - Qing Tang; Ying Yang; Jia’nan Sun (Human Cell, 2025)

Human metapneumovirus: a mini-review on the genetic and phylogenetic roots of a rising respiratory threat - Pooja Tiwary; Krishil Oswal; Ryan Varghese; Harsh Anchan (Human Cell, 2025)

Potential of platelet-rich plasma-derived exosomes for bone-defect repair: in vitro and in vivo study - Xuepu Zhang; Limin Yang; Yaguang Wang; Zhaoliang Ban; Xiaohu Ma; Qiangqiang Zhang; Yue Zhang (Human Cell, 2025)

Establishment and characterization of TK-DDCS1: a novel IDH1 mutated dedifferentiated chondrosarcoma cell line - Krittamate Saisuwan; Piyanard Boonnate; Hiroki Goto; Rumi Nakagawa; Makoto Abe; Kaoru Hirabayashi; Yukio Fujiwara; Kazutaka Kikuta; Seiji Okada (Human Cell, 2025)