Establishment and comparison of three sublines from a human uterine carcinosarcoma cell line, ESCA - Yixiu Long; Xuan Pei; Hongyu Liu; Xueyan Ouyang; Wei Jiang; Huijuan Yang (Human Cell, 2025)
The pathogenesis of uterine carcinosarcoma (UCS) remains unclear due to a few mature cell lines. Herein, we established a new cell line, ESCA, from a Chinese woman. Especially, three sublines, named ESCA-2, ESCA-3, ESCA-5, were isolated based on the rate of cells’ different sedimentation. All ESCA cells have been subcultured for more than 60 generations. ESCA sublines display different cell morphology and growth characteristics, as well as have different sensitivity to chemotherapeutic drugs. ESCA was most sensitive to paclitaxel and carboplatin, while ESCA-2 was most sensitive to ifosfamide. Besides, ESCA showed severe chromosome karyotype abnormalities and abnormal number of chromosomes. Whole exome sequence showed ESCA and its sublines, as well as tissue block shared similar single nucleotide variants, such as TP53 , TRRAP mutations, while relatively large differences in mutational signature abundance. When all ESCA cells were xenotransplanted subcutaneously into BALB/c-nu mice, they developed into tumors that resembled the original tumor with positive AE1/3 and Vimentin in immunohistochemical staining. Interestingly, the transplanted tumor from ESCA-5 proliferated fastest with a relatively low level of glucose uptake evaluated by micro-PET/CT scanning. Taken together, ESCA and its sublines may be valuable tools to explore the molecular mechanism of UCS .

Hypoxic breast cancer cell-derived exosomal miR-143-3p targets RICTOR to regulate M2 macrophage polarization, thereby modulating cancer cell invasiveness - Hongyu Lian; Miao Yu; Qi Li; Jiayi Xiao; Xin Tang; Bin Zhang; Dongxue Liu; Yongliang Xu; Mo Dong; Zitao Li; Lihong Yao; Caijuan Li (Human Cell, 2025)

Biological functions and molecular mechanisms of circHIPK3 in digestive system tumors - Jian Li; Xin Su; Xiao Xu; Youbao Ye; Cailiu Wang; Ang Liu; Changchun Zhao; Wenxiu Liu; Liwen Yang; Tao Wang; Xiangyong Hao (Human Cell, 2025)

KS-NailMel-1: a novel cell line of nail apparatus melanoma - Takamichi Ito; Yuka Tanaka; Keiko Tanegashima; Kiichiro Nishio; Hiroki Hashimoto; Toshio Ichiki; Fumitaka Ohno; Yumiko Kaku-Ito; Takeshi Nakahara (Human Cell, 2025)
Nail apparatus melanoma (NAM) is a specific type of cutaneous melanoma that develops in the nail apparatus of the hands and feet. The prognosis for metastatic NAM is poor due to a lack of fully effective systemic therapies. However, the difficulty in obtaining a NAM model has hindered basic research aimed at discovering effective treatment strategies. In this study, we established a NAM cell line, named KS-NailMel-1, from a primary tumor located on the nail apparatus of the left ring finger of a 68-year-old Japanese female. The cells were successfully maintained for over 9 months, exhibiting a doubling time of 38.6 ± 1.94 h. KS-NailMel-1 displayed consistent growth, spheroid formation, and invasiveness, and was confirmed to be identical to the original tumor through short tandem repeat analyses, whole-exome sequencing, and immunohistochemistry. Western blotting of the cells demonstrated the protein expression of NECTIN4, which has recently attracted attention as a potential therapeutic target for melanoma. The KS-NailMel-1 cell line represents a valuable resource for basic and preclinical research on NAM, deepening our understanding of the tumor characteristics and facilitating the development of treatment strategies for this rare form of cancer.

Mesenchymal stem/stromal cells-derived exosomes: possible therapeutic mechanism in inflammatory bowel disease - Zekun Li; Luyun Liu; Yuhui Sun; Xinjuan Liu; Ping Zhang; Yue Wang; Gang Ding (Human Cell, 2025)

Single-cell dynamic RNA and glycosylation sequencing reveals the mechanism underlying the differentiation of pluripotent stem cells into hematopoietic stem cells - Wanyi Feng; Sheng Zeng; Donghui Liu; Wei Gong; Junjie Hu; Weihua Xu; Zhichao Ma; Shengmiao Fu; Xinping Chen (Human Cell, 2025)
Studying the mechanism of hematopoietic stem cells’ generation from induced pluripotent stem cells in vitro can be useful for understanding embryonic hematopoiesis, as well as for the application of related cell therapy. This study aimed to delineate the process of the differentiation of induced pluripotent stem cells into hematopoietic stem cells’ models and provide a theoretical basis and clinical value for the production of hematopoietic stem cells in vitro. We analyzed the differentiation model by single-cell dynamic transcriptome and glycosylation sequencing, which was divided into three differentiation stages based on the new‐to‐total RNA ratio and glycosylation level. Two differentiation fates were found in the pseudo-time, including hematopoietic development and other tissue development. Precursor hematopoietic cells with a high glycosylation level greatly expressed hematopoietic regulation and vascular endothelial genes, suggesting that glycosylation is associated with angiogenesis and hematopoietic regulation. The multiple differentiation events in the in vitro model are similar to those in hematopoietic development in vivo, including yolk sac hematopoiesis, cellular communication between non-potential hematopoietic subsets and potential hematopoietic subsets, gene expression, and temporal deviations in hematopoietic fate. Our study has revealed the similar hematopoiesis process in the differentiation model via single-cell dynamic RNA and glycosylation sequencing, which provides an important theoretical basis for the study of hematopoietic stem cell development.

Establishment and characterization of NCC-MLPS4-C1: a novel patient-derived cell line of myxoid liposarcoma - Julia Osaki; Rei Noguchi; Takuya Ono; Yuki Adachi; Shuhei Iwata; Yomogi Shiota; Hiroya Kondo; Koichi Ogura; Shogo Nishino; Akihiko Yoshida; Akira Kawai; Tadashi Kondo (Human Cell, 2025)

Establishment and molecular characterization of the novel cutaneous squamous cell carcinoma cell line from advanced-stage Indian patient - Darshan Mehta; Akshay Paradkar; Prakash Nayak; Bharat Rekhi; Bhabani Mohanty; Pradip Chaudhari; Sanjeev K Waghmare (Human Cell, 2025)
Cutaneous squamous cell carcinoma (CSCC) is the second most prevalent skin cancer with low metastatic potential; it poses significant morbidity challenges. CSCC possesses significant heterogeneity and the treatment presents a formidable challenge. To gain a clear insight into the diverse nature of these tumors, the development of an in vitro cell line model is essential. However, there are few cell lines that were established, and only one skin SCC cell line is available on the ATCC. In the present study, we established and characterized a novel ACSCC1 cell line from the advanced-stage treatment naïve cutaneous SCC originating from the forearm of the Indian patient. The keratin expression profile showed the epithelial origin of the cell line, ploidy and karyotyping revealed the hyperdiploid population; ACSCC1 showed an increased tumorigenic and metastatic potential. Further, our cell line showed higher invasive, migratory potential and epithelial-mesenchymal-transition (EMT). Additionally, the Transmission electron microscopy (TEM) results showed an aberrant mitochondrial morphology and reduction in the cellular junctions. Further, our whole genome sequencing (WGS) analysis showed mutations in the cancer-related genes. Overall, the novel ACSCC1 cell line can be used to decipher the molecular signaling in the cancer stem cells (CSCs); targeting the CSCs population may help in understanding the tumor recurrence.

The glycocalyx: a key target for treatment of severe acute pancreatitis-associated multiple organ dysfunction syndrome - Huijuan Li; Haiyun Wen; Jie Liu; Xinyu Luo; Boliang Pei; Peng Ge; Zhenxuan Sun; Jin Liu; Junjie Wang; Hailong Chen (Human Cell, 2025)
The endothelial glycocalyx is a dynamic brush-like layer composed of proteoglycans and glycosaminoglycans, including heparan sulfate (HS) and hyaluronic acid (HA), and is an important regulator of vascular homeostasis. Its structure (thickness ranges from 20 to 6450 nm in different species) not only provides a charge-selective barrier but also serves to anchor mechanosensors such as the glypican-1 (GPC-1)/caveolin-1 (CAV-1) complex and buffers shear stress. In severe acute pancreatitis (SAP), inflammatory factors promote the expression of matrix metalloproteinases (MMPs) and heparinases, which degrade syndecan-1 (SDC-1) and HS, while oxidative stress disrupts HA-CD44 binding, leading to increased capillary leakage and neutrophil adhesion. This degradation process occurs before the onset of multiple organ dysfunction syndrome (MODS), highlighting the potential of the glycocalyx as an early biomarker. More importantly, the regeneration of glycocalyx through endothelial cell synthesis of glycosaminoglycans (GAGs) and shear stress-driven SDC recycling provides therapeutic prospects. This review redefines the pathophysiology of severe acute pancreatitis-associated multiple organ dysfunction (SAP-MODS) by exploring the glycocalyx’s central mechanistic role and proposes stabilizing glycocalyx structure as a potential strategy to prevent microcirculatory failure. Graphical Abstract

KDELR3 is transcriptionally activated by FOXM1 and accelerates lung adenocarcinoma growth and metastasis via inhibiting endoplasmic reticulum stress-induced cell apoptosis - Cheng Wang; Zhaoxuan Wang; Shiqing Wang; Lin Jing; Chundong Gu (Human Cell, 2025)

ITGA5 drives angiogenesis in diabetic retinopathy via TAK-1/NF-kB activation - Feifei Kan; Di Wang; Sijia Li; Yi Gao; Jianwen Wang (Human Cell, 2025)

Secretory pathway in honeybee venom and actin: evidence from chemical–biological interactions - Amr Ahmed El-Arabey (Human Cell, 2025)

Potential reverse functions of GOLPH3 and GOLPH3L in pyroptotic cell death, with implications in resistance to radiotherapy and chemotherapy - Caglar Berkel (Human Cell, 2025)

Establishment and characterization of patient-derived tongue squamous cell carcinoma cell lines - Priyanka Joshi; Sanjay Bane; Pankaj Chaturvedi; Poonam Gera; Sanjeev K. Waghmare (Human Cell, 2025)
Oral squamous cell carcinoma (OSCC) is a common carcinoma in Indian population, wherein one-third of global OSCC cases are from India. The five-year survival rate is poor due to late diagnosis. Oral tongue squamous cell carcinoma (OTSCC) is the second-most common OSCC. An in vitro cell line model is a valuable tool to get a deeper understanding of the molecular mechanisms involved in therapy resistance and disease progression. We report establishment of three OTSCC cell lines from advanced stage treatment naïve Indian patient samples, such as ACOTSC120, ACOSTC132, and ACOTSC140. All three OTSCC cell lines showed epithelial morphology, which was confirmed by Keratin-14 staining. The cell lines showed in vitro spheroid-forming and in vivo tumorigenic potential. The STR of the cell lines ensured their human origin and novelty when compared to DSMZ cell line database. The karyotype of the cell lines showed aneuploidy and further confirmed their human origin. These cell lines showed the presence of cancer stem cell (CSCs) population, i.e., the ALDH br /CD44 + population. These cell lines thus provide a model to help understand the biology of disease and its progression.

The role of microglia in the development of diabetic retinopathy and its potential clinical application - Tingting Lu; Jiameng shang; Shengdan Pu; Yuxin Xu; Xiaotong Sun; Xinyuan Gao (Human Cell, 2025)

Sunitinib-resistant renal cell carcinoma cell-derived exosomes promote facilitation of tumor progression via secretion of the lncRNA SNHG16 - WeiLijiang Saimaiti; Jun Ma; Paluoke Dilimulati; Yujie Wang (Human Cell, 2025)

Advanced glycation end products alter the structural integrity, increase the permeability and transform the biocompatibility of collagen within the peritoneal membrane - Makoto Fukuda; Yusuke Chiwata; Takayuki Narita; Maki Yoshihara; Hiroyuki Morimoto; Ayako Takamori; Shota Shibuki; Rinko Hinami; Ayano Ishibashi; Akinori Nagashima; Motoaki Miyazono; Shigehisa Aoki (Human Cell, 2025)

Establishment and characterization of Cri Du Chat neuronal stem cells: a novel promising resource to study the syndrome - Giovanna Piovani; Rosalba Monica Ferraro; Silvia Clara Giliani (Human Cell, 2025)
The Cri Du Chat (CdC) Syndrome is a rare chromosome disease condition resulting from variable size deletion occurring on the short arm of one of the chromosomes 5. This disorder, which affects one in 50,000 births, is responsible for developmental retardation, the mechanism of which has remained unexplained. TERT, SEMA5 A, CTNND2, TPPP, mapped in chromosome 5 short arm, are known to be expressed in the brain, and to play a role in the development of the nervous system, oligodentrocytes and in the regulation of glutamatergic and dopaminergic synaptic transmission. It is critical to understand how their haploinsufficiency might affect the development and presentation of the disease. In the absence of an animal model and of significant accessible, human tissue, human pluripotent stem cells (iPSC) directly reprogrammed from patient somatic cells open a new area of disease modeling as they can virtually be differentiated into any cell type. Our study reports, for the first time, the generation of neuronal stem cells (NSCs) from CdC-iPSCs line and in addition, subsequent differentiation into a heterogeneous population of neurons. Gene expression of the mentioned and single copy deleted genes was also evaluated by comparing their expression level in iPSC, NSCs and neuron lines. The present research represents the first and the most innovative approach, to create an in vitro CdC neuronal model to have a new translational framework to study the pathologic processes.

Screening of pivotal oncogenes modulated by DNA methylation in hepatocellular carcinoma and identification of atractylenolide I as an anti-cancer drug - Yang Zhi; Tong Qiaoyun (Human Cell, 2025)

Deficiency of synaptotagmin-1 aggravates pressure overload-induced cardiac hypertrophy and dysfunction via the p38 MAPK signaling pathway in mice - Jing Shen; Junqiu Miao; Lifei Wu; Deping Wang; Guang Li; Haixiong Wang; Jimin Cao (Human Cell, 2025)
Cardiac hypertrophy is a major risk factor for heart failure and sudden cardiac death, but its molecular mechanisms have not been well clarified. Synaptotagmin-1 (SYT1) is an important regulator of exocytosis and apoptosis and has been found expressed in the myocardium, while its functions in heart diseases have rarely been studied. Here, we investigated the role and mechanism of SYT1 in pressure overload-induced cardiac hypertrophy. Transverse aortic constriction (TAC) surgeries were performed to induce cardiac hypertrophy in global Syt1 knockout ( Syt1 +/− ) mice and C57BL/6J wild-type (WT) littermates in vivo, with respective sham mice as negative controls. Cardiomyocyte hypertrophy was induced by angiotensin II (Ang II) in H9C2 cells in vitro. The results showed that SYT1 expression was significantly upregulated in WT-TAC mice and in Ang II-treated H9C2 cells. Blocking angiotensin receptor by losartan decreased SYT1 expression in Ang II-treated H9C2 cells. Syt1 +/− mice showed significantly exacerbated cardiac hypertrophy, dysfunction, fibrosis, apoptosis and phosphorylation of myocardial p38 MAPK in response to TAC compared to WT mice. Knocking down SYT1 using siRNA in H9C2 cells aggravated Ang II-induced cell hypertrophy and apoptosis, and also enhanced p38 MAPK phosphorylation. Inhibition of p38 MAPK by SB203580 significantly alleviated the hypertrophy and apoptosis in Ang II-treated H9C2 cells. We conclude that deficiency of SYT1 aggravates pressure overload-induced cardiac hypertrophy via the p38 MAPK signaling pathway. The study elucidates a novel role of SYT1 in cardiac remodeling.

Generation of human induced pluripotent stem cell lines derived from a patient carrying an intragenic deletion in the NFIA gene - Ning Zhou; Shengnan Zhang; Chunli Wang; Bixia Zheng; Aihua Zhang; Wei Zhou (Human Cell, 2025)

Retraction Note: RCC2 contributes to tumor invasion and chemoresistance to cisplatin in hepatocellular carcinoma - Qingmin Chen; Peiqiang Jiang; Baoxing Jia; Yahui Liu; Ze Zhang (Human Cell, 2025)

Establishment and characterization of NCC-PS2-C1: a novel cell line of high-grade pleomorphic spindle cell sarcoma, most consistent with myxofibrosarcoma - 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)

Hyaluronic acid-modified milk exosomes carrying ZNF516 inhibit ABCC5 and contribute to pemetrexed sensitivity in lung adenocarcinoma - Hui Li; Yanyan Sun; Jue Wang; Zhiwu Wang; Lan Wu; Jie Lei; Ying Gao (Human Cell, 2025)

LncRNA OLMALINC promotes osteosarcoma progression through USP1-mediated autophagy suppression - Jianping Li; Bo Yu; Zhaowen Xue; Yiping Liang; Shanchuang Chen; Tao Gui; Zitao Liu; Lei Zhang; Rui Peng (Human Cell, 2025)

Clinical characteristics and induced pluripotent stem cells (iPSCs) disease model of Harel–Yoon syndrome caused by compound heterozygous ATAD3A variants - Ziyi Jiang; Hongyu Chen; Xianghong Zhang; Xiaoling Jiang; Zhengqing Tong; Jingjing Ye; Shanshan Shi; Xucong Shi; Fengxia Li; Weiqin Shao; Qiang Shu; Lan Yu (Human Cell, 2025)

The role of MICAL2 in cancer progression: mechanisms, challenges, and therapeutic potential - Ruiying Wang; Zhijuan Hou; Xiao Gao; Binyan Wu; Huizheng Hu; Hongpei Wu (Human Cell, 2025)

SIX1 enhances aerobic glycolysis and progression in cervical cancer through ENO1 - Xuelian Liu; Hang Ren; Anjin Wang; Ziyan Liang; Su Min; Shijie Yao; Shimeng Wan; Yang Gao; Hua Wang; Hongbing Cai (Human Cell, 2025)

The influence of cell source on the senescence of human mesenchymal stem/stromal cells - Seyed Mehdi Hoseini; Fateme Montazeri (Human Cell, 2025)

RFX5 promotes the progression of triple-negative breast cancer through transcriptional activation of JAG1 - Chenhao Li; Xin Wang; Dongliang Shi; Meng Yang; Wenhua Yang; Liang Chen (Human Cell, 2025)

Ovarian Leydig cells and neural crests - José-Luis Carrasco‑Juan; Olga Tapia; Miriam González‑Gómez; Abian Vega-Falcón; Sonia García‑Hernández; Alexis Rufino-Gómez; Rafael Méndez-Medina; Hugo Álvarez-Arguelles Cabrera (Human Cell, 2025)
In our search for markers to identify and study ovarian Leydig cells, we utilized immunohistochemical techniques and visualized the results using conventional and confocal microscopy. We successfully employed steroidogenic factor- 1 (SF1), androgen receptor (AR), and class III β-tubulin as markers. SF1 and AR specifically highlighted the intraneural cell precursors of Leydig cells, which were previously identified in a published case of mature cystic teratoma of the ovary, and the adult ovarian Leydig cells. Furthermore, the transient expression of class III β-tubulin could be associated with the intraneural displacement of these precursors, cooperating in their migration to colonize the ovaries of adult women.

In vitro properties of four benign meningioma cells derived from WHO grade 1 meningiomas - Thanawat Trasaktaweesakul; Pundit Asavaritikrai; Krajang Talabnin; Dusit Kongnawakul; Sukanya Tastub; Pitchanun Jaturutthaweechot; Nopporn Naewwan; Chutima Talabnin (Human Cell, 2025)

LINC01559: roles, mechanisms, and clinical implications in human cancers - Shuwen Zhang; Xin Lan; Ling Lei (Human Cell, 2025)

Establishment and characterization of novel cancer cachexia-inducing cell line, Aku60GC, of scirrhous gastric cancer - Rei Noguchi; Kazuyoshi Yanagihara; Yuki Iino; Teruo Komatsu; Takanori Kubo; Takuya Ono; Julia Osaki; Yuki Adachi; Shuhei Iwata; Yomogi Shiota; Toshio Seyama; Tadashi Kondo (Human Cell, 2025)

Establishment and characterization of NCC-OS2-C1: a novel patient-derived cell line of osteosarcoma - Shuhei Iwata; Rei Noguchi; Julia Osaki; Yuki Adachi; Yomogi Shiota; Koichi Ogura; Shogo Nishino; Akihiko Yoshida; Seiji Ohtori; Akira Kawai; Tadashi Kondo (Human Cell, 2025)

Non-muscle myosin heavy chain IIA regulates cell morphology, stress fibre structure, and cell migration in FLO-1 oesophageal adenocarcinoma cells - Deirdre Duff; Siobhan Gargan; Aideen Long (Human Cell, 2025)
The incidence of oesophageal adenocarcinoma (OAC) is increasing at a rapid rate in Western countries. Early oesophageal cancer is often asymptomatic and metastatic disease is common at presentation leading to poor prognosis and survival rates. Cell migration is tightly controlled in the healthy cell but can become dysregulated in diseases such as OAC where increased cell motility and migration can contribute to metastasis. We investigated the role of an actin-based molecular motor, non-muscle myosin heavy chain IIA (NMHCIIA) in the migratory capacity of oesophageal adenocarcinoma cells. Immunofluorescence microscopy and ratiometric imaging demonstrated that NMHCIIA co-localises with F-actin at the leading edge and retracting rear of migrating FLO-1 OAC cells. siRNA-mediated depletion of NMHCIIA from FLO-1 cells altered cell morphology, gave rise to an increased number of stress fibre like structures and reduced FLO-1 cell migration. These findings suggest that NMHCIIA influences FLO-1 cell migration by regulating F-actin dynamics and the actin cytoskeleton, providing insight into the mechanisms of migration employed by OAC cells and identifying NMHCIIA as a potential therapeutic target for this disease.

The causal dance: trimethylamine N-oxide, obesity, and acute pancreatitis in pathophysiological harmony - Jie Liu; Peng Ge; Yalan Luo; Hailong Chen (Human Cell, 2025)

Establishment and characterization of NCC-dCS2-C1: a novel patient-derived cell line of dedifferentiated chondrosarcoma - Shuhei Iwata; Takuya Ono; Rei Noguchi; Julia Osaki; Yuki Adachi; Yomogi Shiota; Suguru Fukushima; Shogo Nishino; Akihiko Yoshida; Seiji Ohtori; Akira Kawai; Tadashi Kondo (Human Cell, 2025)

Correction: Curzerenone inactivates the nuclear factor-kappa B signaling to suppress malignancy and immune evasion in cervical cancer by targeting CSNK2B - Yangyan Sun; Min Wang; Jing Ling; Qunying Wu; Guorong Han; Junxu Zhou (Human Cell, 2025)

Advances in the study of single-walled carbon nanotubes in ophthalmology - Junyu Wang; Ying Su; Feng Wang (Human Cell, 2025)

Correlation between levels of clock protein expression and effects on temozolomide-resistant glioblastoma and tumor progression - Keng-Liang Kuo; Shu-Jyuan Chang; Aij-Lie Kwan; Chee-Yin Chai (Human Cell, 2025)

Generation and characterization of human-induced pluripotent stem cell lines from patients with autism spectrum disorder and SCN2A variants - John Lenon de Souza Santos; Bruno Diaz Paredes; Corynne Stephanie Ahouefa Adanho; Carolina Kymie Vasques Nonaka; Katia Nunes da Silva; Ian Marinho Santos; Erick Correia Loiola; Viviane Aline Oliveira Silva; Clarissa Araújo Gurgel Rocha; Bruno Solano de Freitas Souza (Human Cell, 2025)

Azoramide, a novel regulator, favors adipogenesis against osteogenesis through inhibiting the GLP-1 receptor-PKA-β-catenin pathway - Zhao Yan; Banjun Ruan; Zheng Zhu; Xiaorui Cao; Zifan Lu (Human Cell, 2025)
The reciprocal fate decision of mesenchymal stem cells (MSCs) to either bone or adipocytes is determined by Wnt-related signaling and the glucagon-like peptide-1 receptor (GLP-1R). Azoramide, an ER stress alleviator, was reported to have an antidiabetic effect. In this study, we investigated the function of azoramide in regulating the lineage determination of MSCs for either adipogenic or osteogenic differentiation. Microcomputed tomography and histological analysis on bone morphogenetic protein (BMP)2-induced parietal periosteum bone formation assays, C3H10T1/2 and mouse bone marrow MSC-derived bone formation and adipogenesis assays, and specific staining for bone tissue and lipid droplets were used to evaluate the role of azoramide on the lineage determination of MSC differentiation. Cells were harvested for Western blot and quantitative real-time polymerase chain reaction (PCR), and immunofluorescence staining was used to explore the potential mechanism of azoramide for regulating MSC differentiation. Based on MSC-derived bone formation assays both in vivo and in vitro, azoramide treatment displayed a cell fate determining ability in favor of adipogenesis over osteogenesis. Further mechanistic characterizations disclosed that both the GLP-1R agonist peptide exendin-4 (Ex-4) and GLP-1R small interfering (si)RNA abrogated azoramide dual effects. Moreover, cAMP-protein kinase A (PKA)-mediated nuclear β-catenin activity was responsible for the negative function of azoramide on bone formation in favor of adipogenesis. These data provide the first evidence to show that azoramide may serve as an inhibitor against GLP-1R in MSC lineage determination.

Establishment and characterization of novel patient-derived esophageal tumoroids with long-term cultivability - Takashi Urano; Etsuko Yokota; Miki Iwai; Takuro Yukawa; Yoshio Naomoto; Nagio Takigawa; Hideyo Fujiwara; Takashi Akiyama; Minoru Haisa; Takuya Fukazawa; Tomoki Yamatsuji (Human Cell, 2025)

Generation of iPSCs line from patient with Singleton-Merten syndrome - Anna Belyaeva; Kseniya Perepelina; Evdokia Kuznetsova; Daria Smirnova; Tatyana Yakovleva; Victoria Turilova; Irina Neganova; Alla Shatrova; Yuliya Fomicheva; Olga Peregudina; Elena Vasichkina; Anna Kostareva; et al. (Human Cell, 2025)

Role of hepatocellular senescence in the development of hepatocellular carcinoma and the potential for therapeutic manipulation - Pramudi Wijayasiri; Stuart Astbury; Grace Needham; Philip Kaye; Mamatha Bhat; Anna M. Piccinini; Aloysious D. Aravinthan (Human Cell, 2025)
Accumulation of senescent hepatocytes is universal in chronic liver disease (CLD). This study investigates an association between hepatocyte senescence and hepatocellular carcinoma (HCC) and explores the therapeutic role of sirolimus. Background liver biopsies from 15 patients with cirrhosis and HCC and 45 patients with cirrhosis were stained for p16, a marker of cell senescence. STAM™ mice were randomized into 3 groups of 5 at 4 weeks of age and administered vehicle ± sirolimus intraperitoneally, thrice weekly, from 4 to 18 weeks of age. Placebo group was an administered vehicle, early sirolimus group was an administered vehicle with sirolimus, late sirolimus group was an administered vehicle from 4 to 12 weeks then vehicle with sirolimus from 12 to 18 weeks. The primary outcome was HCC nodule development. Senescent hepatocyte burden and senescence-associated secretory phenotype (SASP) factors were assessed in mice livers. In the human study, age (OR 1.282, 95% CI 1.086–1.513, p = 0.003) and p16 (OR 1.429, 95% CI 1.112–1.838, p = 0.005) were independently associated with HCC. In the animal study, all three groups exhibited similar MASLD activity scores ( p = 0.39) and fibrosis area ( p = 0.92). The number and the maximum diameter of HCC nodules were significantly lower in the early sirolimus group compared to placebo and late sirolimus group. The gene expression of SASP factors was similar in all groups. Protein levels of some SASP factors (TNFα, IL1β, IL-2, CXCL15) were significantly lower in sirolimus administered groups compared to placebo group. The study demonstrates an independent association between senescent hepatocyte burden and HCC. It indicates a potential chemoprophylactic role for sirolimus through SASP factor inhibition. These early results could inform a future human clinical trial. Graphical abstract

Derivation of functional neurons from induced pluripotent stem cells using a simple neuromesodermal progenitor generation and rapid spinal cord neuron differentiation process - Selinay Şenkal-Turhan; Ezgi Bulut-Okumuş; Fikrettin Şahin; Yavuz Yavuz; Bayram Yılmaz; Hatice Burcu Şişli; Sadık Kalaycı; Hüseyin Buğra Özgün; Zehra Ömeroğlu Ulu; Pınar Akkuş Süt; Ayşegül Doğan (Human Cell, 2025)

In vitro generation of spiral ganglion neurons from embryonic stem cells - Oluwafemi S. Agboola; Meng Deng; Zhengqing Hu (Human Cell, 2025)

Circ_0090100 induces AHNAK expression to inhibit trophoblast cell proliferation and invasion and accelerate cell apoptosis by segregating miR-139-5p in preeclampsia - Zhenli Shan; Linfang Zhou; Yan Ma; Yiying Huang (Human Cell, 2025)

STX1A regulates ferroptosis and chemoresistance in gastric cancer through mitochondrial function modulation - Yan Niu; Chunyu Liu; Lizhou Jia; Fangxin Zhao; Yixiao Wang; Lu Wang; Weiyi Chen; Yanzi Gan; Yongjun Wen (Human Cell, 2025)

Replication factor C4, which is regulated by insulin-like growth factor 2 mRNA binding protein 2, enhances the radioresistance of breast cancer by promoting the stemness of tumor cells - Xiao-Yu Zhu; Pi-Song Li; Hui Qu; Xing Ai; Zi-Ting Zhao; Jia-Bei He (Human Cell, 2025)

Novel CRISPR-Cas9 iPSC knockouts for PCCA and PCCB genes: advancing propionic acidemia research - Emilio M. García-Tenorio; Mar Álvarez; Mónica Gallego-Bonhomme; Lourdes R. Desviat; Eva Richard (Human Cell, 2025)
Propionic acidemia (PA) is a rare autosomal recessive metabolic disorder caused by mutations in the PCCA and PCCB genes, which encode subunits of the mitochondrial enzyme propionyl-CoA carboxylase (PCC). This enzyme deficiency leads to the accumulation of toxic metabolites, resulting in severe metabolic dysfunction. To create ideal in vitro disease models of PA with isogenic controls and provide a robust platform for therapeutic research, we generated two induced pluripotent stem cell (iPSC) lines with knockout (KO) mutations in the PCCA and PCCB genes using CRISPR-Cas9 gene editing in a healthy control iPSC line. The KO iPS cells were successfully established and characterized, confirming the presence of frameshift insertions and deletions in each target gene, as well as the loss of the corresponding transcript, protein expression, and activity. Additionally, the generated iPSC lines exhibit hallmark characteristics of pluripotency, including the potential to differentiate into all three germ layers. Our PCCA and PCCB KO iPSC models provide a valuable tool for studying the molecular mechanisms underlying PA and hold potential for advancing new therapeutic approaches.

Poly(I:C) signaling induces robust CXCL10 production and apoptosis in human esophageal squamous cell carcinoma cells - Yusuke Sato; Akari Yamaya; Kento Sonoda; Akiyuki Wakita; Yushi Nagaki; Ryohei Sasamori; Yoshihiro Sasaki; Takatoshi Yoneya; Shu Nozaki; Tsukasa Takahashi; Misako Matsumoto; Tsukasa Seya; et al. (Human Cell, 2025)
We previously reported that high tumoral expression of Toll-like receptor 3 (TLR3) and CXCL10, a member of the CXC chemokine family, was an independent positive prognostic factor in patients with advanced thoracic esophageal squamous cell carcinoma (ESCC). However, the direct relationships between TLR3 and CXCL10 in ESCC cells was not fully understood. Here, we analyzed TLR3 mRNA and protein expression in two ESCC lines (TE8 and KYSE180) and one esophageal adenocarcinoma (EAC) line (OE19). We also assessed the effect of the TLR3 agonist poly(I:C) on production of downstream adapter proteins and cytokines, including CXCL10, and further tested its effects on cell viability and caspase 3/7 activity with and without siRNA-induced knockdown of TLR3 and the TICAM-1 or MAVS adapter protein. Both ESCC lines, but not the EAC line, showed high expression of TLR3 mRNA and protein. TICAM-1 and MAVS were also expressed, and their knockdown suppressed responsiveness to poly(I:C) in the ESCC lines. Poly(I:C) induced strong CXCL10 production, resulting in significantly upregulated caspase3/7 activity and downregulated cell proliferation in both ESCC lines but not the EAC line. The effect of poly(I:C) on CXCL10 production was attenuated after transfecting the cells with siRNAs targeting TICAM-1 or MAVS. TLR3 is thus highly expressed in ESCC cells, where it induces strong CXCL10 production and significantly upregulates caspase3/7 activity and downregulates cell proliferation. TLR3 signaling and the resultant downstream CXCL10 production have the potential to serve as useful prognostic markers and therapeutic targets for the treatment of ESCC.

MTHFD2 stabilizes LOX expression through RNA methylation modification to promote sepsis-induced acute kidney injury progression - Shudong Sun; Baoyi Han; Guohui Ren; Lei Fan; Junchao Sun; Huiling Li; Jiyi Huang (Human Cell, 2025)

Fetal adnexa-derived allogeneic mesenchymal stem cells for cardiac regeneration: the future trend of cell-based therapy for age-related adverse conditions - Fazel Gorjipour; Sepideh Bohloolighashghaei; Mohammadjavad Sotoudeheian; Hamidreza Pazoki Toroudi (Human Cell, 2025)

CircTBCK protects against osteoarthritis by regulating extracellular matrix and autophagy - Wei Wang; Yuzhe Sun; Peng Tang; Rui Zhang; Yufeng Jiang; Hongwei Min; Chen Gao (Human Cell, 2025)
Osteoarthritis (OA) is a widespread chronic bone and joint disease for which there is currently no effective preventive or therapeutic treatment. Accumulating evidence indicates that circular RNAs (circRNAs), a class of noncoding RNAs, play critical roles in OA. Therefore, in this study, we aimed to reveal an unexplored circTBCK and elucidate its mechanism of action in the pathological process of OA. The different expression of circTBCK was obtained both in vitro and in vivo. In the in vivo model, mice were induced via destabilization of the medial meniscus (DMM) surgery, while in vitro model, mouse cells like primary chondrocytes of newborn mice and ATDC5 cell line were treated with IL-1β treatment (10 ng/mL for 24 h). The level of circTBCK was examined by quantitative real-time polymerase chain reaction (qRT-PCR). After circTBCK was overexpressed or knocked down, IL-1β treatment was performed, and then, chondrocyte viability was detected via a Cell Counting Kit-8 (CCK-8) assay at 0, 24, 48, or 72 h. To assess type II collagen (Collagen II) expression, immunofluorescence (IF) analysis was used. The levels of mRNAs and proteins related to proliferation, the extracellular matrix (ECM) and autophagy were determined by qRT-PCR and Western blotting. Compared with OA treatment, primary chondrocytes with treatment of both circTBCK overexpression and IL-1βincreased the expression of anabolic factors—Collagen II and SRY-box transcription factor 9 (SOX9), proliferation-related molecules—Ki-67 and proliferating cell nuclear antigen (PCNA), and autophagy-related molecules—Microtubule-associated protein 1 light chain 3 (LC3), B-cell lymphoma 1 (Bcl1), and autophagy-related 5 (Atg5) and decreased Sequestosome 1 (SQSTM1 or P62). In contrast, knockdown of circTBCK aggravated the chondrocyte degeneration induced by IL-1β. Overall, our findings suggest that circTBCK, an unexplored circRNA, could regulate autophagy, proliferation, and the extracellular matrix (ECM) to mitigate the development of OA, suggesting a possible target for OA prevention and therapy.

β-Hydroxybutyrate mitigates the detrimental effects of high glucose in human retinal pigment epithelial ARPE-19 cells - Francesca Argentino; Marta Mallardo; Ciro Costagliola; Aurora Daniele; Ersilia Nigro (Human Cell, 2025)
High glucose leads to cellular damage and dysfunction in the retina. Dietary interventions, including the use of ketogenic diets, have been explored for their potential to reduce the adverse effects of hyperglycemia. β-Hydroxybutyrate (BHB), a ketone body, has immune and anti-inflammatory properties. This study aims to investigate whether BHB ameliorates the harmful effects induced by high glucose in ARPE-19 cells, a model of retinal pigment epithelium. We investigated the effects induced by high glucose and/or BHB on viability, migration, colony-forming ability, cell cycle progression and cytokine production. Our data indicate that high glucose significantly reduces the viability of ARPE-19 cells with no significant changes in apoptosis or autophagy, while inducing cell cytostasis. On the other hand, BHB exerts a protective effect on ARPE-19 cells under hyperglycemic conditions improving cell viability and alleviating glucose-induced cell cycle arrest. Additionally, BHB treatment affects the expression of IL-8 and IL-17α, as well as of MCP-1, modulating the inflammatory response, cell migration and wound healing. In conclusion, this study highlights the potential protective role of BHB against the detrimental effects induced by high glucose on ARPE-19 cells. These findings support the use of ketone bodies in mitigating high glucose-induced cellular damage. Future research will be critical to translate these findings to the clinical practice for metabolic diseases.

Extrachromosomal circular DNA: a double-edged sword in cancer progression and age-related diseases - Shadira Anindieta Irdianto; Astari Dwiranti; Anom Bowolaksono (Human Cell, 2025)

Exploring the therapeutic potential of MOTS-c in age-related macular degeneration: from cellular responses to patient-derived cybrids - Zahra Mohtashami; Kevin Schneider; Reza Azimi; Shari Atilano; Marilyn Chwa; M. Cristina Kenney; Mithalesh Kumar Singh (Human Cell, 2025)

Relevance of mitochondrial morphological changes in keratoconus patients undergoing collagen cross-linking and deep anterior lamellar keratoplasty - Shivam Sharma; Lata Singh; Tapas Chandra Nag; Seema Kashyap; Seema Sen; Chanda Panwar; Mithalesh Kumar Singh; Namrata Sharma (Human Cell, 2025)

Immunomodulatory role of exosome-derived content in pediatric medulloblastoma: a molecular subgroup perspective - Jessica Oliveira de Santis; Graziella Ribeiro de Sousa; Rosane Gomes de Paula Queiroz; Marina Ferreira Cândido; Fausto Almeida; Caroline Patini de Rezende; Patricia Cassia de Ruy; Gabriel Santos Arini; Beth Coyle; Philippa Wade; María Sol Brassesco; Carlos Alberto Scrideli; et al. (Human Cell, 2025)

Derivation of hiPSC line (ICADRB2i007-A-3) from an individual with osteoporosis linked to ADRB2: c.46G > A - O. Krasnova; P. Semenova; A. Kovaleva; J. Sopova; V. Turilova; T. Yakovleva; O. Bystrova; M. Martynova; I. Neganova (Human Cell, 2025)

Long noncoding RNA SNHG4 promotes glioma progression via regulating miR-367-3p/MYO1B axis in zebrafish xenografts - Yueqing Zhang; Yongjin Wang; Yang Yang; Chunming Sun (Human Cell, 2025)
Glioma is one of the most malignancy and prevalent tumor in the human central nervous system, which is associated with severe morbidity and high mortality. Numerous studies have explained the clear correlation between abnormal expression of lncRNA and progression of Glioma. LncRNA small nucleolar RNA host gene 4 (SNHG4) have been proved to play oncogenesis roles in various tumors, however, the underlying mechanism remains to be explored deeply. In this study, by analysis of the public database, we found that SNHG4 was upregulated in multiple cancer tissues, including glioma. Subsequently, the functional roles of SNHG4 were investigated, and we found that knockdown of SNHG4 remarkedly inhibited cell proliferation, migration. While, overexpression of SNHG4 enhanced these functions of glioma cells in vitro. Meanwhile, as the in vivo tool, zebrafish xenograft model was used to verify the functions of SNHG4 in glioma cells. Mechanically, we identified that SNHG4 or MYO1B could bind with miR-367-3p by the luciferase reporter assays. Furthermore, the rescue experiments showed that the inhibition of miR-367-3p or the expression of MYO1B partially rescue the inhibition effects of SNHG4 in glioma cells. Our study reveals that SNHG4 promotes the proliferation, migration of glioma via regulating miR-367-3p/MYO1B axis.

Differentiation of human hyalocytes from induced pluripotent stem cells through ascorbic acid treatment - Elena Laura Mazzoldi; Gabriele Benini; Rosalba Monica Ferraro; Moira Micheletti; Giovanni Martellosio; Viola Balduchelli; Piergiuseppe Sacristani; Daniele Lussignoli; Francesco Semeraro; Sara Rezzola; Marco Presta; Loredana Bergandi; et al. (Human Cell, 2025)
Hyalocytes are macrophage-like cells residing in the eye vitreous cortex. Even though hyalocytes have been firstly described in the mid-Nineteenth century, they have been poorly explored. Recent researches highlighted hyalocyte involvement in both physiological and pathological processes of the vitreoretinal interface. Nonetheless, the majority of works involving hyalocyte cultures were carried out in animals, while fewer studies were performed on humans because their isolation requires vitrectomy. The aim of this study was to differentiate human induced pluripotent stem cells (iPSCs) into hyalocytes as a non-invasive method to continuously obtain cells. iPSCs were first differentiated into hematopoietic stem/progenitor cells (HSPCs) and then into macrophages. Macrophages were either left untreated (NT) or treated with ascorbic acid (AA) alone or combined with bFGF and/or TGF-β1. Additionally, macrophages were cultured in the presence of a pool of vitreous bodies from vitrectomies. Cells were analyzed for morphology and then for gene and protein expression through qRT-PCR, immunofluorescence, Western Blot, and flow cytometry. Similar to cells treated with the vitreous body, macrophages treated with AA alone or in combination with bFGF exhibited a more elongated shape compared to NT or cells treated with TGF-β1. Additionally, these treatments resulted in gene expression downregulation for S100A4 , S100A10 , S100B , and CX3CR1 , while upregulating COL6A1 , HLA-DRA , and CD74 . At the protein level, S100B, CD14, and CD49d were downregulated with all treatments, while collagen VI and HLA-DR were upregulated. This work demonstrates that hyalocytes can be differentiated by treatment of iPSC-derived macrophages with ascorbic acid for a period of 21 days.

The miR-1305/KLF5 negative regulatory loop affects pancreatic cancer cell proliferation and apoptosis - Yufu Zhou; Yulin Tang; Feizhou Huang; Zhichao Wang; Zhengbin Wen; Qi Fang; Changfa Wang (Human Cell, 2025)

Twist2 knockdown alleviates renal ischemia–reperfusion injury by maintaining mitochondrial function and enhancing mitophagy through Bnip3 - Lexi Zhang; Jianfeng Ye; Cheng Qiu (Human Cell, 2025)

Establishment and characterization of NCC-SFT1-C1: a novel patient-derived cell line of solitary fibrous tumor - Shuhei Iwata; Rei Noguchi; Julia Oosaki; Yuki Adachi; Yomogi Shiota; Eisuke Kobayashi; Toshiyuki Takemori; Shogo Nishino; Akihiko Yoshida; Seiji Ohtori; Akira Kawai; Tadashi Kondo (Human Cell, 2025)

The role of RhoA-ROCK signaling in benign prostatic hyperplasia: a review - Shidong Shan; Min Su (Human Cell, 2025)

Establishment of a human ovarian endometrioid carcinoma cell line by constitutive expression of cyclin-dependent kinase 4, cyclin D1 and telomerase reverse transcriptase - Hitomi Hoshino; Tomoya O. Akama; Daisuke Inoue; Suzuko Moritani; Shohei Shigeto; Kazuyuki Matsuda; Hisato Yoshida; Natsumi Yonemoto; Mana Fukushima; Yoshio Yoshida; Motohiro Kobayashi (Human Cell, 2025)
Only a few human ovarian endometrioid carcinoma cell lines are currently available, partly due to the difficulty of establishing cell lines from low-grade cancers. Here, using a cell immortalization strategy consisting of i) inactivation of the p16 INK4a -pRb pathway by constitutive expression of mutant cyclin-dependent kinase 4 (R24C) (CDK4 R24C ) and cyclin D1, and ii) acquisition of telomerase reverse transcriptase (TERT) activity, we established a human ovarian endometrioid carcinoma cell line from a 46-year-old Japanese woman. That line, designated JFE-21, has proliferated continuously for over 6 months with a doubling time of ~ 55 h. JFE-21 cells exhibit polygonal shapes and proliferate without contact inhibition to form a monolayer in a jigsaw puzzle-like arrangement. Ultrastructurally, JFE-21 cells exhibit well-developed rough endoplasmic reticulum, mitochondria and lysosomes in the cytoplasm, with cells contacting each other via desmosomes. G-band karyotype analysis indicated that cells had a near-tetraploid karyotype. Immunofluorescence staining revealed that the expression profile of a series of ovarian carcinoma markers in JFE-21 cells was consistent with ovarian endometrioid carcinoma. Moreover, Sanger sequencing of DNA polymerase ε ( POLE ) gene and immunohistochemical analysis of mismatch repair (MMR) proteins revealed that JFE-21 cells were classified as the no specific molecular profile (NSMP) subtype. In addition, JFE-21 cells were sensitive to paclitaxel and carboplatin administered to the donor as therapy. These findings indicate that constitutive expression of CDK4 R24C , cyclin D1 and TERT genes may be an option to establish cell lines from low-grade cancers, including ovarian endometrioid carcinoma.

Nimodipine ameliorates subarachnoid hemorrhage-induced neuroinflammation and injury by protecting mitochondrial function and regulating autophagy - Liqiu Ma; Lan Yao; Zhaowei Zhang; Bing Hao (Human Cell, 2025)

The multifaceted roles of aldolase A in cancer: glycolysis, cytoskeleton, translation and beyond - Shiyi Yu; Yaji Xue; Yongli Chen; Yuanye Cao; Yawen Yang; Xiaoyu Ge; Xinting Cai (Human Cell, 2025)

Inhibitory effects of the combination of rapamycin with gemcitabine plus paclitaxel on the growth of pancreatic cancer tumors - Yuri Jobu; Miki Nishigawa; Kaoru Furihata; Mutsuo Furihata; Kazushige Uchida; Keisuke Taniuchi (Human Cell, 2025)
We previously examined the antitumor effects of short interfering RNA nanoparticles targeting mammalian target of rapamycin (mTOR) in an orthotopic pancreatic cancer mouse model. We herein report the inhibitory effects of the mTOR inhibitor rapamycin on tumor growth in a novel established mouse model of pancreatic cancer using human pancreatic cancer cell line-derived organoids. Gemcitabine, 5-fluorouracil, and gemcitabine plus nab-paclitaxel are clinically used to treat advanced pancreatic cancer. In vitro assays showed that rapamycin strongly inhibited cell invasion, while gemcitabine, 5-fluorouracil, and gemcitabine plus paclitaxel primarily inhibited cell proliferation with minimal effects on invasion. In vivo mouse experiments demonstrated that rapamycin exhibited superior antitumor activity to S-1 (a metabolically activated prodrug of 5-fluorouracil) and another mTOR inhibitor, everolimus, while its efficacy was similar to that of gemcitabine plus paclitaxel (which was used instead of nab-paclitaxel due to concerns about allergic reactions in mice to human albumin) in a mouse model of pancreatic cancer using human pancreatic cancer cell line-derived organoids. Furthermore, the combination of rapamycin with gemcitabine plus paclitaxel exerted synergistic inhibitory effects on the growth of pancreatic cancer tumors. Although the inhibition of tumor growth was significantly stronger in everolimus-treated mice than in control mice, there were no additive anti-growth effects when combined with gemcitabine plus paclitaxel. The present results suggest that the combination of rapamycin with gemcitabine plus paclitaxel achieved the greatest reduction in tumor volumes in the mouse xenograft model and, thus, has significant clinical promise.

High glucose induces renal tubular epithelial cell senescence by inhibiting autophagic flux - Ying Zhang; Yu Zhao; Yu-Qiu Liu; Ya-Ping Fang; Li Sun; Shan-Zhai Wei; Xiao-Dong Zhu; Xiao-Liang Zhang (Human Cell, 2025)

The dual role of PTPN22 in immune modulation and transplantation tolerance - Beyza Goncu; Ali Osman Gurol (Human Cell, 2025)

Modeling the lymph node stromal cells in oral squamous cell carcinoma: insights into the stromal cues in nodal metastasis - Bonney Lee James; Shaesta Naseem Zaidi; R. K. Aiswarya; Vivek Shetty; R. Vidya Bhushan; Yogesh Dokhe; B. S. Naveen; Vijay Pillai; Sujan K. Dhar; Moni Abraham Kuriakose; Amritha Suresh (Human Cell, 2025)

Identification of a novel GRHPR mutation in primary hyperoxaluria type 2 and establishment of patient-derived iPSC line - Xiang Yan; Zihao Xu; Yue Chen; Langping Gao; Zige Jiang; Lexin Liu; Guozhen Wang; Xiangjun Chen; Chengpeng Wu; Lidan Hu (Human Cell, 2025)

Human amniotic epithelial stem cells, a potential therapeutic approach for diabetes and its related complications - Zhenshuo Chen; Yunfei Luo; Jianping Liu (Human Cell, 2025)

Taxifolin regulates SLC31A1-mediated cuproptosis and tumor progression in hepatocellular carcinoma - Jike Li; Yuelian Wang; Lei Bao; Guo Chen; Qing Ye; Chengshi He; Lin Liu; Mei Luo (Human Cell, 2025)

Long non-coding RNA MSC-AS1 confers imatinib resistance of gastrointestinal stromal tumor cells by activating FNDC1 and ANLN-mediated PI3K/AKT pathway - Lin Chen; Yongjian Gao; Huaixi Yang; Yanzhuo Su; Yunxin Zhang; Lin Lou; Xuefeng Wang; Dayong Ding (Human Cell, 2025)

Loss of hepatocyte growth factor activator inhibitor type 1 (HAI-1) upregulates MMP-9 expression and induces degradation of the epidermal basement membrane - Liang Weiting; Makiko Kawaguchi; Tsuyoshi Fukushima; Yuichiro Sato (Human Cell, 2024)

Curzerenone inactivates the nuclear factor-kappa B signaling to suppress malignancy and immune evasion in cervical cancer by targeting CSNK2B - Yangyan Sun; Min Wang; Jing Ling; Qunying Wu; Guorong Han; Junxu Zhou (Human Cell, 2024)

Bone marrow stromal cell antigen 2 is broadly expressed in the different pluripotent states of human pluripotent stem cells and regulates the expression of pluripotency genes and three germ layer markers - Hong Seo Choi; Ji Yoon Lee; Mun Ju Choi; Min Seong Kim; Chun Jeih Ryu (Human Cell, 2024)

β-Asarone regulates microglia polarization to alleviate TBI-induced nerve damage via Fas/FasL signaling axis - Mingyue Xia; Min Yi; Chunyuan Guo; Yeli Xie; Wenting Yu; Dongsheng Wang; Xingping Dai (Human Cell, 2024)

MiR-34a regulates renal circadian rhythms during cisplatin-induced nephrotoxicity - Mohnad Abdalla; Amr Ahmed El-Arabey; Zhongtao Gai (Human Cell, 2024)

Exosomal miR-146a-5p derived from bone marrow mesenchymal stromal cells regulate Th1/Th2 balance and alleviates immune thrombocytopenia in pregnancy - Yanyan Rong; Wei Lu; Xianbao Huang; Dexiang Ji; Dehong Tang; Ruibin Huang; Wenhua Zhou; Guoan Chen; Yue He (Human Cell, 2024)

N6-methyladenosine-modified SRD5A3, identified by IGF2BP3, sustains cisplatin resistance in bladder cancer - Kai Liao; Jing Li; Caixian He; Jiyong Peng (Human Cell, 2024)
Resistance to cisplatin-based chemotherapy limits the clinical benefit to some bladder cancer patients, and understanding the epigenetic regulation mechanism of cisplatin (CDDP) resistance in bladder cancer from the perspective of N6-methyladenosine (m6A) modification may optimize CDDP-based treatments. The study identified SRD5A3 as an oncogene for bladder cancer and stabilized by a m6A reader, IGF2BP3, to sustain CDDP resistance. Our results revealed that the expression of SRD5A3 was elevated in human bladder cancer tissues and cell lines, and this elevation was more evident in CDDP-resistant T24 and 5637 cells. Results of CCK-8 assay, colony formation assay, EdU staining, and flow cytometric analysis revealed that SRD5A3 knockdown and IGF2BP3 knockdown reduced cell proliferation and prevented chemoresistance in CDDP-resistant T24 and 5637 cells. Results of methylated RNA immunoprecipitation-PCR, RNA immunoprecipitation assay, and luciferase reporter assay showed IGF2BP3 recognized the SRD5A3 m6A modification and stabilized its mRNA. Nude mice implanted subcutaneously with CDDP-resistant T24 cells were injected intraperitoneally with CDDP (2 mg/kg) every 3 days for 35 days and the results demonstrated that SRD5A3 knockdown and IGF2BP3 knockdown effectively inhibited the tumor growth in subcutaneous implantation model. Collectively, the study unveils that IGF2BP3-mediated SRD5A3 m6A modification facilitates bladder cancer progression and induces CDDP resistance, providing rational therapeutic targets for bladder cancer patients.

Establishment and characterization of NCC-GCTB10-C1: a novel cell line derived from a patient with recurrent giant cell tumor of bone - Yuki Adachi; Rei Noguchi; Julia Osaki; Takuya Ono; Taro Akiyama; Hiroya Kondo; Eisuke Kobayashi; Naoki Kojima; Akihiko Yoshida; Hideki Yokoo; Akira Kawai; Tadashi Kondo (Human Cell, 2024)

Establishment and characterization of a novel patient-derived cell line from conventional central grade 3 chondrosarcoma, NCC-CS1-C1 - Rei Noguchi; Takuya Ono; Julia Osaki; Yuki Adachi; Shuhei Iwata; Yomogi Shiota; Kazuyoshi Yanagihara; Shogo Nishino; Takaya Funada; Koichi Ogura; Akihiko Yoshida; Akira Kawai; et al. (Human Cell, 2024)

Establishment of two novel organoid lines from patients with combined hepatocellular cholangiocarcinoma - Yun Gao; Xiaoyun Chen; Yuerong Zhu; Suiqing Zhou; Long Zhang; Qiuyue Wu; Hui Zhang; Ziyi Wang; Xuejiao Chen; Xinyi Xia; Liyong Pu; Xuehao Wang (Human Cell, 2024)

Emerging role of exosomes during the pathogenesis of viral hepatitis, non-alcoholic steatohepatitis and alcoholic hepatitis - Congjian Shi; Shuang Hu; Shen Liu; Xiaodi Jia; Yubin Feng (Human Cell, 2024)

Establishment and characterization of the novel myxofibrosarcoma cell line, SMU-MFS - Naoya Nakahashi; Makoto Emori; Kohichi Takada; Yasutaka Murahashi; Junya Shimizu; Kazuyuki Murase; Tomohide Tsukahara; Shintaro Sugita; Akira Takasawa; Kousuke Iba; Atsushi Teramoto; Makoto Osanai (Human Cell, 2024)

Molecular leveraging of HOX-embedded non-coding RNAs in the progression of acute myeloid leukemia - Christine Wilson; Priyanka Swaroop; Sachin Kumar; Anita Chopra; Surender K. Sharawat (Human Cell, 2024)

ZC3H13 promotes autophagy in bladder cancer through m6A methylation modification of PJA2 and ubiquitination of KSR1 - Beibei Liu; Mengjie Chen; Yujie Liang; Zhijie Mei; Wei Sun; Wuyue Gao; Tiantian Zhang; Rui Wang; Yuanyuan Guo (Human Cell, 2024)

Establishment of a novel benign meningioma cell line spontaneously immortalized under hypoxic conditions - Takaaki Ishikawa; Masahide Matsuda; Hiroshi Ishikawa; Junko Toyomura; Akihiro Ohyama; Noriaki Sakamoto; Alexander Zaboronok; Eiichi Ishikawa (Human Cell, 2024)

Mesenchymal stem/stromal cells: dedicator to maintain tumor homeostasis - Juncun Yao; Li Sun; Feng Gao; Wei Zhu (Human Cell, 2024)

Establishment and characterization of NCC-GCTB14-C1 and NCC-GCTB15-C1: two novel patient-derived cell lines of giant cell tumor of bone - Shuhei Iwata; Takuya Ono; Rei Noguchi; Julia Osaki; Yuki Adachi; Yomogi Shiota; Shintaro Iwata; Shogo Nishino; Akihiko Yoshida; Seiji Ohtori; Akira Kawai; Tadashi Kondo (Human Cell, 2024)

In Vitro differentiation of hair-follicle bulge stem cells into synaptophysin-expressing neurons: a potential new approach for neuro-regeneration - Mohamad Mahjoor; Maliheh Nobakht; Fatemehsadat Ataei Kachouei; Hamidreza Zalpoor; Fatemeh Heidari; Abazar Yari; Sanaz Joulai Veijouye; Hojjatollah Nazari; Nayereh Sajedi (Human Cell, 2024)

Generation of human induced pluripotent stem cell lines derived from patients of cystic biliary atresia - Ningxin Ge; Kan Suzuki; Iori Sato; Michiya Noguchi; Yukio Nakamura; Mami Matsuo-Takasaki; Jun Fujishiro; Yohei Hayashi (Human Cell, 2024)
Biliary atresia (BA), resulting from abnormal development of the liver’s internal or external bile ducts, can lead to liver damage and potentially fatal cirrhosis. Type I cystic biliary atresia is a relatively uncommon, but clinically significant variant of BA. It is critical to develop experimental models of BA to examine the etiology and pathogenesis, which remain elusive, and to develop future therapeutics. Here, we have successfully generated a panel of human induced pluripotent stem cells (hiPSCs) from five Japanese patients carrying type I cystic BA. These hiPSC lines exhibited characteristics of self-renewal and pluripotency. These cells held normal karyotypes mostly, but one of them carried hemizygous deletions, the clinical significance of which is unknown yet. Whole genome sequence analysis indicated that some of the mutations or single nucleotide polymorphisms (SNPs) commonly found in these patients are related to hepatobiliary abnormality. Given the limited understanding of the molecular pathogenesis of cystic BA, attributed to unknown factors of genetic and environmental causes, these cellular resources will be instrumental in replicating disease phenotypes and in advancing novel therapies for this disease.

Pancreatic cancer-derived exosomal miR-510 promotes macrophage M2 polarization and facilitates cancer cell aggressive phenotypes - Tao Wang; Lin Ye; Yingjie Zhou; Xionghan Zhang; Renjian Li; Yi Zhou; Jun Weng; Qingrong Mo; Yaqun Yu (Human Cell, 2024)

Strong genetic effect on gout revealed by genetic risk score from meta-analysis of two genome-wide association studies - Akiyoshi Nakayama; Yusuke Kawamura; Masahiro Nakatochi; Yu Toyoda; Mayuko Nakajima; Kazuki Maehara; Mana Kirihara; Seiko Shimizu; Keitaro Matsuo; Hirotaka Matsuo; Toru Shimizu; Hiroshi Ooyama; et al. (Human Cell, 2024)

Identification of novel gout loci from trans-ethnic meta-analysis of serum urate level - Yusuke Kawamura; Akiyoshi Nakayama; Masahiro Nakatochi; Yuka Aoki; Yu Toyoda; Takahiro Nakamura; Seiko Shimizu; Keitaro Matsuo; Nariyoshi Shinomiya; Hirotaka Matsuo; Ken Yamamoto; Toru Shimizu; et al. (Human Cell, 2024)

Pathophysiology, molecular mechanisms, and genetics of atrial fibrillation - Pan Han; Xinxin Zhao; Xuexun Li; Jing Geng; Shouxiang Ni; Qiao Li (Human Cell, 2024)

Establishment and drug resistance characterization of paired organoids using human primary colorectal cancer and matched tumor deposit specimens - Jiao Deng; Jerry H. Qin; Xiaolan Li; Deding Tao; Yongdong Feng (Human Cell, 2024)
Tumor deposits (TDs) represent a specific form tumor metastasis observed in colorectal cancer (CRC). The lack of successfully established cell lines for TDs, as well as the molecular mechanisms by which TDs occur remain largely unknown. Here, we established paired CRC organoids, including a human primary cancer organoid and its TD organoid, from a 46-year-old male patient with CRC. Further analysis revealed that, compared with primary tumor-derived cells, TD-derived cells exhibited enhanced proliferative, invasive and metastatic capabilities, and increased expression of stemness-related proteins. Furthermore, the present findings also demonstrated that TD-derived cells were more resistant to oxaliplatin or 5-FU. Transcriptomic profiling and qPCR revealed that TD-derived cells exhibited more alterations in fatty acid metabolism signaling and enhanced lipid synthesis ability compared to primary tumor-derived cells. Inhibition of lipid synthesis markedly decreased resistance to oxaliplatin in TD-derived cells. Taken together, the paired organoids established using CRC primary tumor and its TD specimens will provide valuable tools to study tumorigenicity, metastasis and chemoresistance in CRC. Notably, these models will provide novel insights to study tumor heterogeneity and lipid metabolism in CRC.

Establishment and characterization of a patient-derived metastatic extraskeletal Ewing sarcoma cell line ES-ZSS-1 - Chenlu Zhang; Mengling Liu; Lijuan Luan; Xi Guo; Yang You; Zhiming Wang; Wei Li; Nanhang Lu; Yingyong Hou; Lili Lu; Weiqi Lu; Yuhong Zhou (Human Cell, 2024)

Emodin regulated lactate metabolism by inhibiting MCT1 to delay non-small cell lung cancer progression - Fei Zhang; Tian Gu; Jin Li; Yanqiu Zhu; Mingliang Chu; Qing Zhou; Jiemin Liu (Human Cell, 2024)

Brain inflammaging in the pathogenesis of late-life depression - Toshiaki Ishizuka; Wataru Nagata; Keiichi Nakagawa; Sayaka Takahashi (Human Cell, 2024)

Adiponectin-induced activation of ERK1/2 drives fibrosis in retinal pigment epithelial cells - Karthikka Palanisamy; Muthuramalingam Karpagavalli; Ragavachetty Nagaraj Nareshkumar; Sharada Ramasubramanyan; Narayanasamy Angayarkanni; Rajiv Raman; Subbulakshmi Chidambaram (Human Cell, 2024)

Assessment of non-myelotoxic agents as a preparatory regimen for hematopoietic stem cell gene therapy - Mehmet Emin Şeker; Özgür Doğuş Erol; Burcu Pervin; Gerard Wagemaker; Niek P. van Til; Fatima Aerts-Kaya (Human Cell, 2024)

MiR-124-3p inhibits cell stemness in glioblastoma via targeting EPHA2 through ALKBH5-mediated m6A modification - Maimaitiyiming Tuoheti; Jinxian Li; Cheng Zhang; Feng Gao; Jichao Wang; Yonggang Wu (Human Cell, 2024)

Generation of CRISPR/Cas9 modified human iPSC line with correction of heterozygous mutation in exon 6 of the CaSR gene - P. I. Semenova; A. V. Panova; J. V. Sopova; O. A. Krasnova; V. I. Turilova; T. K. Yakovleva; K. S. Kulikova; D. A. Petrova; S. L. Kiselev; I. E. Neganova (Human Cell, 2024)

High prevalence of chromosome 17 in breast cancer micronuclei: a means to get rid of tumor suppressors? - Laxmi Kumari; Sreejesh Sreedharanunni; Divya Dahiya; Pranab Dey; Alka Bhatia (Human Cell, 2024)

Interaction of SARS-CoV-2 Spike protein with ACE2 induces cortical actin modulation, including dephosphorylation of ERM proteins and reduction of cortical stiffness - Thi Ly Do; Kouichi Tachibana; Norio Yamamoto; Kiyoshi Ando; Takaaki Isoda; Takanori Kihara (Human Cell, 2024)

Autophagy activation ameliorates the fibrosis of trabecular meshwork cells induced by TGFβ2 through the promotion of fibrotic proteins degradation - Gang Wang; Rumeng Zhao; Zhenyang Guo; Huiling Cui; Di Wang; Jing Ren; Shichao Zhu; Ke Zhang; Bo Tang; Jingyi Zhang; Peng Li; Shichao Duan; et al. (Human Cell, 2024)

Application of hydrogel-loaded dental stem cells in the field of tissue regeneration - Xiaolan Wang; Zejun Zheng; Ying Zhang; Jinmeng Sun; Jian Liu; Yunxia Liu; Gang Ding (Human Cell, 2024)

ST3GAL4 promotes tumorigenesis in breast cancer by enhancing aerobic glycolysis - Xiaoqing Chen; Weijie Su; Jiewen Chen; Peng Ouyang; Jin Gong (Human Cell, 2024)

Inhibition of the AP-1/TFPI2 axis contributes to alleviating cerebral ischemia/reperfusion injury by improving blood–brain barrier integrity - Yue Cao; Ruixian Xing; Qiushi Li; Yang Bai; Xuewen Liu; Buxian Tian; Xin Li (Human Cell, 2024)

Transcription repression of estrogen receptor alpha by ghrelin/Gq/11/YAP signaling in granulosa cells promotes polycystic ovary syndrome - Pengfei Zhu; Xingyu Bi; Dan Su; Xiaoling Li; Yanhua Chen; Zhijiao Song; Lijiang Zhao; Yaoqing Wang; Suming Xu; Xueqing Wu (Human Cell, 2024)

Establishment and characterization of two novel patient-derived cell lines from myxofibrosarcoma: NCC-MFS7-C1 and NCC-MFS8-C1 - Yuki Adachi; Rei Noguchi; Julia Osaki; Takuya Ono; Shuhei Iwata; Taro Akiyama; Ryuto Tsuchiya; Yu Toda; Sekita Tetsuya; Shintaro Iwata; Eisuke Kobayashi; Naoki Kojima; et al. (Human Cell, 2024)

GABAA receptor modulation by the endocannabinoid system: insights into the regulatory mechanisms involving glutamine synthetase and MAPK mediators - Sina Pakkhesal (Human Cell, 2024)

Sequencing-based study of neural induction of human dental pulp stem cells - Shohei Takaoka; Fumihiko Uchida; Hiroshi Ishikawa; Junko Toyomura; Akihiro Ohyama; Hideaki Matsumura; Koji Hirata; Satoshi Fukuzawa; Naomi Ishibashi Kanno; Aiki Marushima; Kenji Yamagata; Toru Yanagawa; et al. (Human Cell, 2024)

Cyclic tensile stress promotes osteogenic differentiation via upregulation of Piezo1 in human dental follicle stem cells - Binqing Xie; Xianyi He; Ye Guo; Jie Shen; Binbin Yang; Rui Cai; Junliang Chen; Yun He (Human Cell, 2024)

The role of monoglyceride lipase gene in promoting proliferation, metastasis, and free fatty acid accumulation in uveal melanoma cells - Yanan Xu; Jiangming Zhong; Zhenhua Liu; Deyu Li (Human Cell, 2024)

Establishment and characterization of NCC-SS6-C1: a novel patient-derived cell line of synovial sarcoma - Julia Osaki; Rei Noguchi; Takuya Ono; Yuki Adachi; Shuhei Iwata; Yu Toda; Takaya Funada; Shintaro Iwata; Naoki Kojima; Akihiko Yoshida; Akira Kawai; Tadashi Kondo (Human Cell, 2024)

Exploring the relationship between ulcerative colitis, colorectal cancer, and prostate cancer - Yurie Kura; Marco A. De Velasco; Kazuko Sakai; Hirotsugu Uemura; Kazutoshi Fujita; Kazuto Nishio (Human Cell, 2024)

Apelin-13 alleviates intrauterine adhesion by inhibiting epithelial–mesenchymal transition of endometrial epithelial cells and promoting angiogenesis - Qun Zhao; Yuyan Li; Xingping Zhao; Jiahui Zhou; Yifan Zheng; Zhiyue Li (Human Cell, 2024)

Osteoarthritis rat serum-derived extracellular vesicles aggravate osteoarthritis development by inducing NLRP3-mediated pyroptotic cell death and cellular inflammation - Zhifang Tang; Longjun Shu; Zijian Cao; Yongqing Xu; Chuan Li (Human Cell, 2024)

Zebrafish larvae as a model for studying the impact of oral bacterial vesicles on tumor cell growth and metastasis - Marjut Metsäniitty; Saika Hasnat; Carina Öhman; Tuula Salo; Kari K. Eklund; Jan Oscarsson; Abdelhakim Salem (Human Cell, 2024)
Oral bacteria naturally secrete extracellular vesicles (EVs), which have attracted attention for their promising biomedical applications including cancer therapeutics. However, our understanding of EV impact on tumor progression is hampered by limited in vivo models. In this study, we propose a facile in vivo platform for assessing the effect of EVs isolated from different bacterial strains on oral cancer growth and dissemination using the larval zebrafish model. EVs were isolated from: wild-type Aggregatibacter actinomycetemcomitans and its mutant strains lacking the cytolethal distending toxin (CDT) or lipopolysaccharide (LPS) O-antigen; and wild-type Porphyromonas gingivalis . Cancer cells pretreated with EVs were xenotransplanted into zebrafish larvae, wherein tumor growth and metastasis were screened. We further assessed the preferential sites for the metastatic foci development. Interestingly, EVs from the CDT-lacking A. actinomycetemcomitans resulted in an increased tumor growth, whereas EVs lacking the lipopolysaccharide O-antigen reduced the metastasis rate. P. gingivalis -derived EVs showed no significant effects. Cancer cells pretreated with EVs from the mutant A. actinomycetemcomitans strains tended to metastasize less often to the head and tail compared to the controls. In sum, the proposed approach provided cost- and labor-effective yet efficient model for studying bacterial EVs in oral carcinogenesis, which can be easily extended for other cancer types. Furthermore, our results support the notion that these nanosized particles may represent promising targets in cancer therapeutics.

Assessing the antitumor effects of metformin on ovarian clear cell carcinoma - Satoshi Takemori; Tohru Morisada; Makoto Osaka; Momoe Watanabe; Atsushi Tajima; Shinji Tanigaki; Yoichi Kobayashi (Human Cell, 2024)

Development of 3D-iNET ORION: a novel, pre-clinical, three-dimensional in vitro cell model for modeling human metastatic neuroendocrine tumor of the pancreas - Jan Strnadel; Mark A. Valasek; Grace Y. Lin; Huahui Lin; Ann M. Ponsford Tipps; Sang Myung Woo; Ken Fujimura; Huawei Wang; Sunkyu Choi; Jack Bui; Christopher Hermosillo; Kristen Jepsen; et al. (Human Cell, 2024)
Neuroendocrine tumors (NETs) of the pancreas are rare neoplasms that present complex challenges to diagnosis and treatment due to their indolent course. The incidence of pancreatic neuroendocrine tumors has increased significantly over the past two decades. A limited number of pancreatic neuroendocrine cell lines are currently available for the research. Here, we present 3D-iNET ORION, a novel 3-dimensional (spheroid) cell line, isolated from human pancreatic neuroendocrine tumor liver metastasis. Three-dimensionally grown (3D) cancer cell lines have gained interest over the past years as 3D cancer cell lines better recapitulate the in vivo structure of tumors, and are more suitable for in vitro and in vivo experiments. 3D-iNET ORION cancer cell line showed high potential to form tumorspheres when embedded in Matrigel matrix and expresses synaptophysin and EpCAM. Electron microscopy analysis of cancer cell line proved the presence of dense neurosecretory granules. When xenografted into athymic mice, 3D-iNET ORION cells produce slow-growing tumors, positive for chromogranin and synaptophysin. Human Core Exome Panel Analysis has shown that 3DiNET ORION cell line retains the genetic aberration profile detected in the original tumor. In conclusion, our newly developed neuroendocrine cancer cell line can be considered as a new research tool for in vitro and in vivo experiments.

In vitro models of the choroid plexus and the blood-cerebrospinal fluid barrier: advances, applications, and perspectives - Christian Schwerk; Horst Schroten (Human Cell, 2024)
The choroid plexus (CP), a highly vascularized endothelial–epithelial convolute, is placed in the ventricular system of the brain and produces a large part of the cerebrospinal fluid (CSF). Additionally, the CP is the location of a blood–CSF barrier (BCSFB) that separates the CSF from the blood stream in the CP endothelium. In vitro models of the CP and the BCSFB are of high importance to investigate the biological functions of the CP and the BCSFB. Since the CP is involved in several serious diseases, these in vitro models promise help in researching the processes contributing to the diseases and during the development of treatment options. In this review, we provide an overview on the available models and the advances that have been made toward more sophisticated and “in vivo near” systems as organoids and microfluidic lab-on-a-chip approaches. We go into the applications and research objectives for which the various modeling systems can be used and discuss the possible future prospects and perspectives.

Carbon quantum dots for the diagnosis and treatment of ophthalmic diseases - Xi Zhang; Liang Yang; Feng Wang; Ying Su (Human Cell, 2024)

Immunomodulatory signalling networks in glioblastoma multiforme: a comprehensive review of therapeutic approaches - Souhrid Sarkar; Somi Patranabis (Human Cell, 2024)

Potential protumor function of CD74 in clear cell renal cell carcinoma - Ayano Ezaki; Hiromu Yano; Cheng Pan; Yukio Fujiwara; Toshiki Anami; Yuki Ibe; Takanobu Motoshima; Junji Yatsuda; Shigeyuki Esumi; Yuji Miura; Tomomi Kamba; Yoshihiro Komohara (Human Cell, 2024)

Establishment and characterization of a novel MDM2/MYCN-co-amplified neuroblastoma cell line, NBN-SHIM, established from a late recurrent stage MS tumor - Keisuke Kato; Jun-ichi Nagai; Hiroaki Goto; Masato Shinkai; Norihiko Kitagawa; Yasunori Toyoda; Toshiji Nishi; Hisato Kigasawa; Mio Tanaka; Kenji Kurosawa; Yumi Ito; Masayuki Haruta; et al. (Human Cell, 2024)

Comparison among different preclinical models derived from the same patient with a non-functional pancreatic neuroendocrine tumor - Yan Wang; Zeng Ye; Xin Lou; Junfeng Xu; Desheng Jing; Chenjie Zhou; Yi Qin; Jie Chen; Xiaowu Xu; Xianjun Yu; Shunrong Ji (Human Cell, 2024)

Nanofiber-based delivery of evodiamine impedes malignant properties of intrahepatic cholangiocarcinoma cells by targeting HDAC4 and restoring TPM1 transcription - Rui Zou; Yiyao Wang; Yaoqing Cai; Zhenming Xing; Yongfu Shao; Duo Li; Chunchun Qi (Human Cell, 2024)

PROX1 is a regulator of neuroendocrine-related gene expression in lung carcinoid - Kouhei Sakurai; Tatsuya Ando; Yasuhiro Sakai; Yuichiro Mori; Satoru Nakamura; Taku Kato; Hiroyasu Ito (Human Cell, 2024)

Extracellular signal-regulated kinase is activated in podocytes from patients with diabetic nephropathy - Aoi Yamashiro; Yasushi Satoh; Shogo Endo; Naoki Oshima (Human Cell, 2024)

Long non-coding RNA SIX1-1 promotes proliferation of cervical cancer cells via negative transcriptional regulation of RASD1 - Xiaoli Hu; Wan Wang; Teng Ma; Wanqi Zhang; Xiaohui Tang; Yingru Zheng; Xiuhui Zheng (Human Cell, 2024)

Establishment and characterization of the PDAC-X3 cell line: a novel Chinese-origin pancreatic ductal adenocarcinoma cell line - Changpeng Chai; Huan Tang; Xin Miao; Yuanhui Su; Lu Li; Cheng Yu; Jianfeng Yi; Zhenzhen Ye; Long Miao; Bo Zhang; Zhengfeng Wang; Wei Luo; et al. (Human Cell, 2024)

NR2F1 overexpression alleviates trophoblast cell dysfunction by inhibiting GDF15/MAPK axis in preeclampsia - Ke Zhang; Hailing Zhang; Bing Wang; Shanshan Gao; Caiping Sun; Cong Jia; Jinquan Cui (Human Cell, 2024)

The function of long non-coding RNA IFNG-AS1 in autoimmune diseases - Jiale Zhao; Yibei Gui; Wei Wu; Xueqing Li; Lijun Wang; Hailin Wang; Yiyang Luo; Gang Zhou; Chengfu Yuan (Human Cell, 2024)

Recent advances in nanomaterials for the treatment of femoral head necrosis - Yalin Yuan; Mi Zou; Shuqin Wu; Congcong Liu; Liang Hao (Human Cell, 2024)

Pathophysiological role of Na–Cl cotransporter in kidneys, blood pressure, and metabolism - Ran You; Zhanjun Jia (Human Cell, 2024)

Mesenchymal stem cells and their extracellular vesicles in bone and joint diseases: targeting the NLRP3 inflammasome - Shuangshuang Xu; Ying Zhang; Zejun Zheng; Jinmeng Sun; Yanan Wei; Gang Ding (Human Cell, 2024)

Derivation of two iPSC lines (KAIMRCi004-A, KAIMRCi004-B) from a Saudi patient with Biotin-Thiamine-responsive Basal Ganglia Disease (BTBGD) carrying homozygous pathogenic missense variant in the SCL19A3 gene - Maryam Alowaysi; Moayad Baadhaim; Mohammad Al-Shehri; Hajar Alzahrani; Amani Badkok; Hanouf Attas; Samer Zakri; Seham Alameer; Dalal Malibari; Manal Hosawi; Mustafa Daghestani; Khalid Al-Ghamdi; et al. (Human Cell, 2024)
The neurometabolic disorder known as biotin-thiamine-responsive basal ganglia disease (BTBGD) is a rare autosomal recessive condition linked to bi-allelic pathogenic mutations in the SLC19A3 gene. BTBGD is characterized by progressive encephalopathy, confusion, seizures, dysarthria, dystonia, and severe disabilities. Diagnosis is difficult due to the disease’s rare nature and diverse clinical characteristics. The primary treatment for BTBGD at this time is thiamine and biotin supplementation, while its long-term effectiveness is still being investigated. In this study, we have generated two clones of induced pluripotent stem cells (iPSCs) from a 10-year-old female BTBGD patient carrying a homozygous mutation for the pathogenic variant in exon 5 of the SLC19A3 gene, c.1264A > G (p.Thr422Ala). We have confirmed the pluripotency of the generated iPS lines and successfully differentiated them to neural progenitors. Because our understanding of genotype–phenotype correlations in BTBGD is limited, the establishment of BTBGD-iPSC lines with a homozygous SLC19A3 mutation provides a valuable cellular model to explore the molecular mechanisms underlying SLC19A3-associated cellular dysfunction. This model holds potential for advancing the development of novel therapeutic strategies.

The origin of ovarian Leydig cells: a possibly solved enigma? - José-Luis Carrasco-Juan; Miriam González-Gómez; Olga Tapia; Sonia García-Hernández; Abian Vega-Falcón; Rafael Méndez-Medina; Hugo Álvarez-Argüelles Cabrera; Lucio Díaz-Flores (Human Cell, 2024)

KIN17 functions in DNA damage repair and chemosensitivity by modulating RAD51 in hepatocellular carcinoma - Xueran Huang; Zichang Dai; Biyun Zeng; Xiangyan Xiao; Kashif Rafiq Zahid; Xiaocong Lin; Tiancai Liu; Tao Zeng (Human Cell, 2024)

The role of neutrophils in chronic cough - Guan-Zhen Xue; Hai-Zhen Ma; Ta-na Wuren (Human Cell, 2024)

A call for standardization for secretome and extracellular vesicles in osteoarthritis: results show disease-modifying potential, but protocols are too heterogeneous—a systematic review - Daniele D’Arrigo; Manuela Salerno; Luca De Marziani; Angelo Boffa; Giuseppe Filardo (Human Cell, 2024)

Adipose-derived stem cells modified by TWIST1 silencing accelerates rat sciatic nerve repair and functional recovery - Bo Chen; Leining Wang; Xiaogui Pan; Shuai Jiang; Yihe Hu (Human Cell, 2024)
The regeneration of peripheral nerves after injury is often slow and impaired, which may be associated with weakened and denervated muscles subsequently leading to atrophy. Adipose-derived stem cells (ADSCs) are often regarded as cell-based therapeutic candidate due to their regenerative potential. The study aims to assess the therapeutic efficacy of gene-modified ADSCs on sciatic nerve injury. We lentivirally transduced ADSCs with shRNA-TWIST1 and transplanted modified cells to rats undergoing sciatic nerve transection and repair. Results showed that TWIST1 knockdown accelerated functional recovery of rats with sciatic nerve injury as faster nerve conduction velocity and higher wire hang scores obtained by rats transplanted with TWIST1-silenced ADSCs than scramble ADSCs. Although the rats experienced degenerated axons and decreased myelin sheath thickness after sciatic nerve injury 8 weeks after operation, those transplanted with TWIST1-silenced ADSCs exhibited more signs of regenerated nerve fibers surrounded by newly formed myelin sheaths than those with scramble ADSCs. The rats transplanted with TWIST1-silenced ADSCs presented increased expressions of neurotrophic factors including neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell line-derived neurotrophic factor (GDNF) in the sciatic nerves than those with scramble ADSCs. These results suggest that genetically modifying TWIST1 in ADSCs could facilitate peripheral nerve repair after injury in a more efficient way than that with ADSCs alone.

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, 2024)

EP300 promotes tumor stemness via epigenetic activation of CRISP3 leading to lobaplatin resistance in triple-negative breast cancer - Yan Wang; Yi Zhang; Xiaowei Qi (Human Cell, 2024)

Re: Identification of a family with van der Hoeve's syndrome harboring a novel COL1A1 mutation and generation of patient-derived iPSC lines and CRISPR/Cas9-corrected isogenic iPSCs - Raymond Dalgleish (Human Cell, 2024)

Synergistic effect of chimeric antigen receptor modified with Bcl-2 on enhanced solid tumour targeting - Xiaoyan Wang; Guodong Liu; Tian Huan; Yuxing Wang; Bo Jiang; Wei Liu; Anran Dai; Xiangzhi Zhang; Feng Yu (Human Cell, 2024)

Delivery of neurotrophin-3 by RVG-Lamp2b-modified mesenchymal stem cell-derived exosomes alleviates facial nerve injury - Wenting Bi; Xiaodan Mu; Yongfeng Li; Qingyan Sun; Lei Xiang; Min Hu; Huawei Liu (Human Cell, 2024)

Targeted inhibition of SUMOylation: treatment of tumors - Hongwei Zhao; Panpan Zhao; Chao Huang (Human Cell, 2024)

Transforming tumoroids derived from ALK-positive pulmonary adenocarcinoma to squamous cell carcinoma in vivo - Etsuko Yokota; Miki Iwai; Yuta Ishida; Takuro Yukawa; Masaki Matsubara; Yoshio Naomoto; Hideyo Fujiwara; Yasumasa Monobe; Minoru Haisa; Nagio Takigawa; Takuya Fukazawa; Tomoki Yamatsuji (Human Cell, 2024)
Approximately 3–5% of non-small cell lung cancers (NSCLC) harbor ALK fusion genes and may be responsive to anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors. There are only a few reports on cell lines with EML4-ALK variant 3 (v3) and tumoroids that can be subject to long-term culture (> 3 months). In this study, we established tumoroids (PDT-LUAD#119) from a patient with lung cancer harboring EML4-ALK that could be cultured for 12 months. Whole-exome sequencing and RNA sequencing analyses revealed TP53 mutations and an EML4-ALK v3 mutation. PDT-LUAD#119 lung tumoroids were sensitive to the ALK tyrosine kinase inhibitors (ALK TKIs) crizotinib, alectinib, entrectinib, and lorlatinib, similar to NCI-H3122 cells harboring EML4-ALK variant 1 (v1). Unexpectedly, clear squamous cell carcinoma and solid adenocarcinoma were observed in xenografts from PDT-LUAD#119 lung tumoroids, indicating adenosquamous carcinoma. Immunostaining revealed that the squamous cell carcinoma was ALK positive, suggesting a squamous transformation of the adenocarcinoma. Besides providing a novel cancer model to support basic research on ALK-positive lung cancer, PDT-LUAD#119 lung tumoroids will help elucidate the pathogenesis of adenosquamous carcinoma.

β-Sitosterol alleviates the malignant phenotype of hepatocellular carcinoma cells via inhibiting GSK3B expression - Ruoyu Wang; Dan Tang; Longyun Ou; Jiacheng Jiang; Yu-nan Wu; Xuefei Tian (Human Cell, 2024)
To explore the effects of β-Sitosterol upon hepatocellular carcinoma cell proliferation, apoptosis, migration, invasion, and epithelial–mesenchymal transition (EMT), and to investigate the underlying mechanism using network pharmacology. Human hepatocellular carcinoma cell lines (Huh-7 and HCCLM3) were expose to gradient concentrations of β-Sitosterol (5 μg/mL, 10 μg/mL, and 20 μg/mL). Cell viability and proliferation were assessed using MTT, CCK-8, colony formation, and EdU assays.Flow cytometry was employed to evaluate cell cycle and apoptosis. Scratch and Transwell assays were performed, respectively, to detect cell migration and invasion. The levels of apoptosis-associated proteins (BAX, BCL2, and cleaved caspase3) as well as EMT-associated proteins (E-cadherin, N-cadherin, Snail, and Vimentin) were detected in Huh-7 and HCCLM3 cell lines using Western blot analysis. The drug target gene for β-Sitosterol was screened via PubChem and subsequently evaluated for expression in the GSE112790 dataset. In addition, the expression level of glycogen synthase kinase 3 beta (GSK3B) within the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) database was analyzed, along with its correlation to the survival outcomes of patients with hepatocellular carcinoma. The diagnostic efficiency of GSK3B was assessed by analyzing the ROC curve. Subsequently, Huh-7 and HCCLM3 cell lines were transfected with the overexpression vector of GSK3B and then treated with β-Sitosterol to further validate the association between GSK3B and β-Sitosterol. GSK3B demonstrated a significantly elevated expression in patients with hepatocellular carcinoma, which could predict hepatocellular carcinoma patients’ impaired prognosis based on GEO dataset and TCGA database. GSK3B inhibitor (CHIR-98014) notably inhibited cell proliferation and invasion, promoted cell apoptosis and cell cycle arrest at G0/G1 phase in hepatocellular carcinoma cells. β-Sitosterol treatment further promoted the efffects of GSK3B inhibitor on hepatocellular carcinoma cells. GSK3B overexpression has been found to enhance the proliferative and invasive capabilities of hepatocellular carcinoma cells. Furthermore it has been observed that GSK3B overexpression, it has been obsear can partially reverse the inhibitory effect of β-Sitosterol upon hepatocellular. β-Sitosterol suppressed hepatocellular carcinoma cell proliferation and invasion, and enhanced apoptosis via inhibiting GSK3B expression.

Immunosuppressive regulatory cells in cancer immunotherapy: restrain or modulate? - Yan Wu; Dongfeng Chen; Yang Gao; Qinggang Xu; Yang Zhou; Zhong Ni; Manli Na (Human Cell, 2024)

Tyndallized bacteria prime bronchial epithelial cells to mount an effective innate immune response against infections - Serena Di Vincenzo; Caterina Di Sano; Claudia D’Anna; Maria Ferraro; Velia Malizia; Andreina Bruno; Marta Cristaldi; Chiara Cipollina; Valentina Lazzara; Paola Pinto; Stefania La Grutta; Elisabetta Pace (Human Cell, 2024)
Airway epithelium represents a physical barrier against toxic substances and pathogens but also presents pattern recognition receptors on the epithelial cells that detect pathogens leading to molecule release and sending signals that activate both the innate and adaptive immune responses. Thus, impaired airway epithelial function and poor integrity may increase the recurrence of infections. Probiotic use in respiratory diseases as adjuvant of traditional therapy is increasingly widespread. There is growing interest in the use of non-viable heat-killed bacteria, such as tyndallized bacteria (TB), due to safety concerns and to their immunomodulatory properties. This study explores in vitro the effects of a TB blend on the immune activation of airway epithelium. 16HBE bronchial epithelial cells were exposed to different concentrations of TB. Cell viability, TB internalization, TLR2 expression, IL-6, IL-8 and TGF-βl expression/release, E-cadherin expression and wound healing were assessed. We found that TB were tolerated, internalized, increased TLR2, E-cadherin expression, IL-6 release and wound healing but decreased both IL-8 and TGF-βl release. In conclusion, TB activate TLR2 pathway without inducing a relevant pro-inflammatory response and improve barrier function, leading to the concept that TB preserve epithelial homeostasis and could be used as strategy to prevent and to manage respiratory infection, exacerbations included.

Biochemical characterization of renal hypouricemia-associated mutations in urate transporter genes using human cells - Yu Toyoda; Tappei Takada; Akiyoshi Nakayama; Nariyoshi Shinomiya; Hirotaka Matsuo (Human Cell, 2024)

Aquaporins in colorectal cancer: exploring their role in tumorigenesis, metastasis, and drug response - Maryam Azimi Mohammadabadi; Ali Moazzeni; Leila Jafarzadeh; Fatemeh Faraji; Amir Hossein Mansourabadi; Elahe Safari (Human Cell, 2024)

DNMT1 driven by mouse amniotic fluid mesenchymal stem cell exosomes improved corneal cryoinjury via inducing microRNA-33 promoter DNA hypermethylation modification in corneal epithelium cells - Weiqi Xu; Xinfeng Fei; Zeyu Cui; Dikang Pan; Yan Liu; Te Liu (Human Cell, 2024)

Generation of induced pluripotent stem cells from an individual with early onset and severe hypertrophic cardiomyopathy linked to MYBPC3: c.772G > A mutation - Marta Ribeiro; Joanna Jager; Marta Furtado; Teresa Carvalho; Joaquim M. S. Cabral; Dulce Brito; Maria Carmo-Fonseca; Sandra Martins; Simão Teixeira da Rocha (Human Cell, 2024)
Hypertrophic cardiomyopathy (HCM) is frequently caused by mutations in the MYPBC3 gene, which encodes the cardiac myosin-binding protein C (cMyBP-C). Most pathogenic variants in MYPBC3 are either nonsense mutations or result in frameshifts, suggesting that the primary disease mechanism involves reduced functional cMyBP-C protein levels within sarcomeres. However, a subset of MYPBC3 variants are missense mutations, and the molecular mechanisms underlying their pathogenicity remain elusive. Upon in vitro differentiation into cardiomyocytes, induced pluripotent stem cells (iPSCs) derived from HCM patients represent a valuable resource for disease modeling. In this study, we generated two iPSC lines from peripheral blood mononuclear cells (PBMCs) of a female with early onset and severe HCM linked to the MYBPC3 : c.772G > A variant. Although this variant was initially classified as a missense mutation, recent studies indicate that it interferes with splicing and results in a frameshift. The generated iPSC lines exhibit a normal karyotype and display hallmark characteristics of pluripotency, including the ability to undergo trilineage differentiation. These novel iPSCs expand the existing repertoire of MYPBC3 -mutated cell lines, broadening the spectrum of resources for exploring how diverse mutations induce HCM. They additionally offer a platform to study potential secondary genetic elements contributing to the pronounced disease severity observed in this individual.

Establishment and characterization of TK-ALCL1: a novel NPM-ALK-positive anaplastic large-cell lymphoma cell line - Prin Sungwan; Jutatip Panaampon; Ryusho Kariya; Satoshi Kamio; Rumi Nakagawa; Toru Hirozane; Yukiko Ogura; Makoto Abe; Kaoru Hirabayashi; Yukio Fujiwara; Kazutaka Kikuta; Seiji Okada (Human Cell, 2024)

Crosstalk among proximal tubular cells, macrophages, and fibroblasts in acute kidney injury: single-cell profiling from the perspective of ferroptosis - Yulin Wang; Ziyan Shen; Shaocong Mo; Han Zhang; Jing Chen; Cheng Zhu; Shiqi Lv; Di Zhang; Xinhui Huang; Yulu Gu; Xixi Yu; Xiaoqiang Ding; et al. (Human Cell, 2024)
The link between ferroptosis, a form of cell death mediated by iron and acute kidney injury (AKI) is recently gaining widespread attention. However, the mechanism of the crosstalk between cells in the pathogenesis and progression of acute kidney injury remains unexplored. In our research, we performed a non-negative matrix decomposition (NMF) algorithm on acute kidney injury single-cell RNA sequencing data based specifically focusing in ferroptosis-associated genes. Through a combination with pseudo-time analysis, cell–cell interaction analysis and SCENIC analysis, we discovered that proximal tubular cells, macrophages, and fibroblasts all showed associations with ferroptosis in different pathways and at various time. This involvement influenced cellular functions, enhancing cellular communication and activating multiple transcription factors. In addition, analyzing bulk expression profiles and marker genes of newly defined ferroptosis subtypes of cells, we have identified crucial cell subtypes, including Egr1 + PTC-C1, Jun + PTC-C3, Cxcl2 + Mac-C1 and Egr1 + Fib-C1. All these subtypes which were found in AKI mice kidneys and played significantly distinct roles from those of normal mice. Moreover, we verified the differential expression of Egr1, Jun, and Cxcl2 in the IRI mouse model and acute kidney injury human samples. Finally, our research presented a novel analysis of the crosstalk of proximal tubular cells, macrophages and fibroblasts in acute kidney injury targeting ferroptosis, therefore, contributing to better understanding the acute kidney injury pathogenesis, self-repairment and acute kidney injury-chronic kidney disease (AKI-CKD) progression.

Interrogating the estrogen-mediated regulation of adrenocortical Klotho expression using ovariectomized albino rat model exposed to repeated restraint stress - Ahmed A. Morsi; Ezat A. Mersal; Ahmed M. Abdelmoneim; Ghaiath Hussein; Mohamed M. Sofii; Khalid Elfaki Ibrahim; Mohamed S. Salim (Human Cell, 2024)

Functional characterization of variants in human ABCC11, an axillary osmidrosis risk factor - Yu Toyoda; Hirotaka Matsuo; Tappei Takada (Human Cell, 2024)

CYTOR-NFAT1 feedback loop regulates epithelial-mesenchymal transition of retinal pigment epithelial cells - Rong Zhang; Lin Wang; Yang Li; Yan Liu; Kui Dong; Yajing Pei; Junmei Zhao; Gang Liu; Jing Li; Xiaodan Zhang; Tong Cui; Yan Gao; et al. (Human Cell, 2024)

Single-cell sequencing advances in research on mesenchymal stem/stromal cells - Qingxi Long; Pingshu Zhang; Ya Ou; Wen Li; Qi Yan; Xiaodong Yuan (Human Cell, 2024)

VBP1 promotes tumor proliferation as a part of the hypoxia-related signature in esophageal squamous cell carcinoma - Huikai Miao; Wuyou Gao; Leqi Zhong; Hongmu Li; Dongni Chen; Chunmei Xu; Zhesheng Wen; Youfang Chen (Human Cell, 2024)
Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor in East Asia. Hypoxia, a hallmark of solid tumors, significantly alters redox homeostasis inside tumor microenvironment. This alteration drives tumor proliferation, invasion, and metastasis, leading to poor prognostic outcomes. However, the role of hypoxia-related genes in ESCC remains poorly understood. We employed RNA sequencing to identify differentially expressed genes in ESCC. Clinical data, transcriptome profiles, and a hypoxia-related gene set were extracted from open-source databases. A prognostic model was constructed using least absolute shrinkage and selection operator (LASSO) regression, which was then validated through Cox regression analysis. Within this prognostic model, we pinpointed and investigated a key hypoxia-related gene affecting prognosis. The gene's expression was validated using real-time PCR and immunohistochemistry in both esophageal carcinoma and normal tissues. Tumor proliferation was examined through in vitro and in vivo assays, including the Cell Counting Kit-8, EdU, colony formation, and subcutaneous tumor models. A robust four-gene prognostic model (VBP1, BGN, CDKN1A, and PPFIA1) was successfully constructed and validated. Among these, VBP1 emerged as a key gene, exhibiting high expression levels that correlated with poor prognosis in ESCC. Functional experiments confirmed that VBP1 significantly accelerated tumor proliferation both in vitro and in vivo. VBP1 is identified as a pivotal gene within the hypoxia-related prognostic signature, and it significantly promotes tumor proliferation in ESCC.

Overexpressing Bcl-2 enhances murine chimeric antigen receptor T cell therapy against solid tumor - Xiaoyan Wang; Guodong Liu; Xianggang Shi; Yuxing Wang; Bo Jiang; Wei Liu; Anran Dai; Xiangzhi Zhang; Feng Yu (Human Cell, 2024)

PMAIP1 regulates autophagy in osteoblasts via the AMPK/mTOR pathway in osteoporosis - Yijie Gao; Anquan Huang; Yantao Zhao; Yunxia Du (Human Cell, 2024)

Developing more comprehensive thyroid cancer organoids for precision medicine - Huihui Yang; Dong Chen (Human Cell, 2024)

Combined use of hydrogen-rich water and enzyme-digested edible bird’s nest improves PMA/LPS-impaired wound healing in human inflammatory gingival tissue equivalents - Dongliang Wang; Naohiro Shimamura; Nobuhiko Miwa; Li Xiao (Human Cell, 2024)

MicroRNA-322-5p targeting Smurf2 regulates the TGF-β/Smad pathway to protect cardiac function and inhibit myocardial infarction - Liping Guo; Ke Li; Yan Ma; Huaiming Niu; Jun Li; Xin Shao; Na Li; Yuehui Sun; Haixiong Wang (Human Cell, 2024)

Genetic diversity among the present Japanese population: evidence from genotyping of human cell lines established in Japan - Fumio Kasai; Makoto Fukushima; Yohei Miyagi; Yukio Nakamura (Human Cell, 2024)
Japan is often assumed to have a highly homogeneous ethnic population, because it is an island country. This is evident in human cell lines collected from cell banks; however, these genotypes have not been thoroughly characterized. To examine the population genotypes of human cell lines established in Japan, we conducted SNP genotyping on 57 noncancerous cell lines and 43 lung cancer cell lines. Analysis of biogeographic ancestry revealed that 58 cell lines had non-admixed Japanese genotypes, 21 cell lines had an admixture of Japanese and East Asian genotypes, and the remaining 21 cell lines had East Asian genotypes. The proportion of non-admixed Japanese genotypes was similar between lung cancer and noncancerous cell lines, suggesting that patients in Japan may not exclusively have Japanese genotypes. This could influence the incidence of inherited diseases and should be taken into account in personalized medicine tailored to genetic background. The genetic makeup of the present-day Japanese population cannot be fully explained by the ancestral Jomon and Yayoi lineages. Instead, it is necessary to consider a certain level of genetic admixture between Japanese and neighboring Asian populations. Our study revealed genetic variation among human cell lines derived from Japanese individuals, reflecting the diversity present within the Japanese population.

Establishment and characterization of novel high mucus-producing lung tumoroids derived from a patient with pulmonary solid adenocarcinoma - Miki Iwai; Etsuko Yokota; Yuta Ishida; Takuro Yukawa; Yoshio Naomoto; Yasumasa Monobe; Minoru Haisa; Nagio Takigawa; Takuya Fukazawa; Tomoki Yamatsuji (Human Cell, 2024)
Among mucus-producing lung cancers, invasive mucinous adenocarcinoma of the lung is a rare and unique subtype of pulmonary adenocarcinoma. Notably, mucus production may also be observed in the five subtypes of adenocarcinoma grouped under the higher-level diagnosis of Invasive Non-mucinous Adenocarcinomas (NMA). Overlapping pathologic features in mucus-producing tumors can cause diagnostic confusion with significant clinical consequences. In this study, we established lung tumoroids, PDT-LUAD#99, from a patient with NMA and mucus production. The tumoroids were derived from the malignant pleural effusion of a patient with lung cancer and have been successfully developed for long-term culture (> 11 months). Karyotyping by fluorescence in situ hybridization using an alpha-satellite probe showed that tumoroids harbored aneuploid karyotypes. Subcutaneous inoculation of PDT-LUAD#99 lung tumoroids into immunodeficient mice resulted in tumor formation, suggesting that the tumoroids were derived from cancer. Xenografts from PDT-LUAD#99 lung tumoroids reproduced the solid adenocarcinoma with mucin production that was observed in the patient's metastatic lymph nodes. Immunoblot analysis showed MUC5AC secretion into the culture supernatant of PDT-LUAD#99 lung tumoroids, which in contradistinction was barely detected in the culture supernatants of NCI-A549 and NCI-H2122 pulmonary adenocarcinoma cells known for their mucin-producing abilities. Here, we established a novel high-mucus-producing lung tumoroids from a solid adenocarcinoma. This preclinical model may be useful for elucidating the pathogenesis of mucus-producing lung cancer.

Cancer-associated fibroblasts-derived exosomal METTL3 promotes the proliferation, invasion, stemness and glutaminolysis in non-small cell lung cancer cells by eliciting SLC7A5 m6A modification - Yafeng Fan; Yanling Yu (Human Cell, 2024)

Polyvinylpyrrolidone can prevent oolemma lysis caused by abnormal rupture of the plasma membrane in Piezo-ICSI - Kohei Mizuno; Osamu Okitsu; Mako Goto; Atsuko Kusuhara; Koji Kusuhara (Human Cell, 2024)

Characterization of immortalized ovarian epithelial cells with BRCA1/2 mutation - Hiroaki Komatsu; Masayo Okawa; Yasuhiro Kazuki; Kanako Kazuki; Genki Hichiwa; Kazuto Shimoya; Shinya Sato; Fuminori Taniguchi; Mitsuo Oshimura; Tasuku Harada (Human Cell, 2024)

Pioglitazone ameliorates ischemia/reperfusion-induced acute kidney injury via oxidative stress attenuation and NLRP3 inflammasome - Zhenfeng Ye; Jing Zhang; Zhou Xu; Zhangwang Li; Gaomin Huang; Bin Tong; Panpan Xia; Yunfeng Shen; Honglin Hu; Peng Yu; Xiaoqing Xi (Human Cell, 2024)

A xenotransplantable malignant deciduoid mesothelioma-cell line, D-Meso-Sonobe - Yuki Hanamatsu; Chiemi Saigo; Hiroshi Sonobe; Tamotsu Takeuchi (Human Cell, 2024)

The effects of exercise on epigenetic modifications: focus on DNA methylation, histone modifications and non-coding RNAs - Junxiong Zhang; Zhongxin Tian; Chao Qin; Mohammad Reza Momeni (Human Cell, 2024)

Establishment of a human ovarian clear cell carcinoma cell line mutant in PIK3CB but not PIK3CA - Hitomi Hoshino; Daisuke Inoue; Akiko Shinagawa; Hisato Yoshida; Shohei Shigeto; Kazuyuki Matsuda; Tomoya O. Akama; Yoshio Yoshida; Motohiro Kobayashi (Human Cell, 2024)
A human ovarian clear cell carcinoma cell line was established from a 46-year-old Japanese woman. That line, designated MTC-22, has proliferated continuously for over 6 months in conventional RPMI 1640 medium supplemented with 10% foetal bovine serum and has been passaged over 50 times. MTC-22 doubling-time is ~ 18 h, which is much shorter than most ovarian clear cell carcinoma lines reported to date. Morphologically, MTC-22 cells exhibit polygonal shapes and proliferate to form a monolayer in a jigsaw puzzle-like arrangement without contact inhibition. Ultrastructurally, cells exhibit numerous intracytoplasmic glycogen granules and well-developed mitochondria. G-band karyotype analysis indicated that cells have a complex karyotype close to tetraploid. We observed that the expression pattern of a series of ovarian carcinoma-related molecules in MTC-22 cells was identical to that seen in the patient’s tumour tissue. Notably, MTC-22 cells, and the patient’s carcinoma tissue, expressed low-sulphated keratan sulphate recognised by R-10G and 294-1B1 monoclonal antibodies, a hallmark of non-mucinous ovarian carcinoma, and particularly of clear cell ovarian carcinoma. Moreover, characteristic point mutations—one in ARID1A , which encodes the AT-rich interaction domain containing protein 1A, and the other in PIK3CB, which encodes the catalytic subunit of phosphoinositide 3-kinase—were seen in the patient’s tumour tissue and retained in MTC-22 cells. Collectively, these findings indicate that MTC-22 cells could serve as a valuable tool for investigating the pathophysiology of ovarian clear cell carcinoma, particularly that harbouring PIK3CB mutations, and for developing and validating new diagnostic and therapeutic approaches to this life-threatening malignancy.

Establishment and molecular characterization of HCB-541, a novel and aggressive human cutaneous squamous cell carcinoma cell line - Ana Carolina Laus; Izabela Natalia Faria Gomes; Aline Larissa Virginio da Silva; Luciane Sussuchi da Silva; Mirella Baroni Milan; Silvia AparecidaTeixeira; Ana Carolina Baptista Moreno Martin; Letícia do Nascimento Braga Pereira; Carlos Eduardo Barbosa de Carvalho; Camila Souza Crovador; Flávia Escremin de Paula; Flávia Caroline Nascimento; et al. (Human Cell, 2024)
Cutaneous squamous cell carcinoma (cSCC) is a common type of skin cancer that can result in significant morbidity, although it is usually well-managed and rarely metastasizes. However, the lack of commercially available cSCC cell lines hinders our understanding of this disease. This study aims to establish and characterize a new metastatic cSCC cell line derived from a Brazilian patient. A tumor biopsy was taken from a metastatic cSCC patient, immortalized, and named HCB-541 after several passages. The cytokeratin expression profile, karyotypic alterations, mutational analysis, mRNA and protein differential expression, tumorigenic capacity in xenograft models, and drug sensitivity were analyzed. The HCB-541 cell line showed a doubling time between 20 and 30 h and high tumorigenic capacity in the xenograft mouse model. The HCB-541 cell line showed hypodiploid and hypotetraploidy populations. We found pathogenic mutations in TP53 p.(Arg248Leu), HRAS (Gln61His) and TERT promoter (C228T) and high-level microsatellite instability (MSI-H) in both tumor and cell line. We observed 37 cancer-related genes differentially expressed when compared with HACAT control cells. The HCB-541 cells exhibited high phosphorylated levels of EGFR, AXL, Tie, FGFR, and ROR2, and high sensitivity to cisplatin, carboplatin, and EGFR inhibitors. Our study successfully established HCB-541, a new cSCC cell line that could be useful as a valuable biological model for understanding the biology and therapy of metastatic skin cancer.

Modulation of the RAC1/MAPK/ERK signalling pathway by farnesyl diphosphate synthase regulates granulosa cells proliferation in polycystic ovary syndrome - Xiaoli Guo; Yijuan Cao; Qing He; Linna Chen; Qing Wang; Jingbo Zhang; Wenqiang Lv; Bei Zhang; Xueyan Zhou (Human Cell, 2024)

Establishment and characterization of multiple patient-derived organoids from a case of advanced endometrial cancer - Yoshiaki Maru; Mami Kohno; Kiyomi Suzuka; Akiko Odaka; Mari Masuda; Akinobu Araki; Makiko Itami; Naotake Tanaka; Yoshitaka Hippo (Human Cell, 2024)

Compensatory upregulation of MT2A alleviates neurogenic intermittent claudication through inhibiting activated p38 MAPK-mediated neuronal apoptosis - Chenggang Wang; Zhanchao Wang; Ying Zi; Xuejian Dan; Jiahui Xu; Jingwei Zhao; Wei Xu; Zhourui Wu; Wei Liu; Bin Ma (Human Cell, 2024)

Pathological mechanisms of cold and mechanical stress in modulating cancer progression - Yun-jing Hou; Xin-xin Yang; Lin He; Hong-xue Meng (Human Cell, 2024)

The significance of m6A RNA methylation regulators in diagnosis and subtype classification of HBV-related hepatocellular carcinoma - Qijuan Zang; Yalin Ju; Siyi Liu; Shaobo Wu; Chengbin Zhu; Liangru Liu; Weicheng Xu; Yingli He (Human Cell, 2024)

The mechanism of the contribution of ICAM-1 to epithelial–mesenchymal transition (EMT) in bladder cancer - Marta Zarzycka; Małgorzata Kotula-Balak; Dorota Gil (Human Cell, 2024)

Prognostic value of inflammation and immune-related gene NOD2 in clear cell renal cell carcinoma - Lei Lyu; Rui Min; Fuxin Zheng; Wei Xiang; Tao Huang; Yan Feng; Chuanhua Zhang; Jingdong Yuan (Human Cell, 2024)

CLLU1 as an emerging biomarker in chronic lymphoid leukemia - Chunmeng Rong; Chenhao Liang; Jinze Shen; Yuhua Zhang; Qurui Wang; Fang Yang; Yalu Chen; Yuqing Luo; Meier Gu; Panpan Gao; Yongming Xia; Shiwei Duan (Human Cell, 2024)

Knockdown of nicotinamide N-methyltransferase suppresses proliferation, migration, and chemoresistance of Merkel cell carcinoma cells in vitro - Valentina Pozzi; Elisa Molinelli; Roberto Campagna; Emma N. Serritelli; Monia Cecati; Edoardo De Simoni; Davide Sartini; Gaia Goteri; Nathaniel I. Martin; Matthijs J. van Haren; Eleonora Salvolini; Oriana Simonetti; et al. (Human Cell, 2024)
Merkel cell carcinoma (MCC) is an aggressive skin cancer, with a propensity for early metastasis. Therefore, early diagnosis and the identification of novel targets become fundamental. The enzyme nicotinamide N -methyltransferase (NNMT) catalyzes the reaction of N -methylation of nicotinamide and other analogous compounds. Although NNMT overexpression was reported in many malignancies, the significance of its dysregulation in cancer cell phenotype was partly clarified. Several works demonstrated that NNMT promotes cancer cell proliferation, migration, and chemoresistance. In this study, we investigated the possible involvement of this enzyme in MCC. Preliminary immunohistochemical analyses were performed to evaluate NNMT expression in MCC tissue specimens. To explore the enzyme function in tumor cell metabolism, MCC cell lines have been transfected with plasmids encoding for short hairpin RNAs (shRNAs) targeting NNMT mRNA. Preliminary immunohistochemical analyses showed elevated NNMT expression in MCC tissue specimens. The effect of enzyme downregulation on cell proliferation, migration, and chemosensitivity was then evaluated through MTT, trypan blue, and wound healing assays. Data obtained clearly demonstrated that NNMT knockdown is associated with a decrease of cell proliferation, viability, and migration, as well as with enhanced sensitivity to treatment with chemotherapeutic drugs. Taken together, these results suggest that NNMT could represent an interesting MCC biomarker and a promising target for targeted anti-cancer therapy.

The role of cardiac microenvironment in cardiovascular diseases: implications for therapy - Jiayu Yao; Yuejun Chen; Yuqing Huang; Xiaoou Sun; Xingjuan Shi (Human Cell, 2024)

Lactate in breast cancer cells is associated with evasion of hypoxia-induced cell cycle arrest and adverse patient outcome - Yamin Liu; Yasir Suhail; Ashkan Novin; Junaid Afzal; Aditya Pant; Kshitiz (Human Cell, 2024)

Establishment and characterization of NCC-ASPS2-C1: a novel patient-derived cell line of alveolar soft part sarcoma - Julia Osaki; Rei Noguchi; Kazuyoshi Yanagihara; Takuya Ono; Yuki Adachi; Shuhei Iwata; Yu Toda; Tetsuya Sekita; Eisuke Kobayashi; Naoki Kojima; Akihiko Yoshida; Akira Kawai; et al. (Human Cell, 2024)

Anexelekto (AXL) no more: microRNA-155 (miR-155) controls the “Uncontrolled” in SARS-CoV-2 - K. I. Papadopoulos; A. Papadopoulou; T. C. Aw (Human Cell, 2024)