Establishment and characterization of two novel patient-derived cell lines from giant cell tumor of bone: NCC-GCTB8-C1 and NCC-GCTB9-C1 - Yuki Adachi; Rei Noguchi; Yuki Yoshimatsu; Yooksil Sin; Julia Osaki; Takuya Ono; Shuhei Iwata; Taro Akiyama; Ryuto Tsuchiya; Yu Toda; Shin Ishihara; Koichi Ogura; et al. (Human Cell, 2024)

Liraglutide prevents cellular senescence in human retinal endothelial cells (HRECs) mediated by SIRT1: an implication in diabetes retinopathy - Lihua Hou; Jianying Du; Yongxiao Dong; Min Wang; Libo Wang; Jifei Zhao (Human Cell, 2024)
Diabetes mellitus (DM) is a chronic metabolic disorder affecting millions of people worldwide, characterized by dysregulated glucose homeostasis and hyperglycemia. Diabetic retinopathy (DR) is one of the serious multisystemic complications. Aging is an important risk factor for DR. Endothelial sirtuin 1 (SIRT1) plays an important role in regulating the pathophysiology of glucose metabolism, cellular senescence, and aging. Liraglutide, an analog of Glucagon-like peptide 1 (GLP-1), has been widely used in the treatment of DM. However, the effects of Liraglutide on DR are less reported. Here, we investigated whether treatment with Liraglutide has beneficial effects on high glucose (HG)-induced injury in human retinal microvascular endothelial cells (HRECs). First, we found that exposure to HG reduced the expression of glucagon-like peptide 1 receptor 1 (GLP-1R). Additionally, Liraglutide ameliorated HG-induced increase in the expression of vascular endothelial growth factor-A (VEGF-A) and interleukin 6 (IL-6). Importantly, Liraglutide ameliorated cellular senescence and increased telomerase activity in HG-challenged HRECs. Liraglutide also reduced the levels of p53 and p21. Mechanistically, Liraglutide restored the expression of SIRT1 against HG. In contrast, the knockdown of SIRT1 abolished the protective effects of Liraglutide in cellular senescence of HRECs. Our findings suggest that Liraglutide might possess a benefit on DR mediated by SIRT1.

Transcription factors in chimeric antigen receptor T-cell development - Anran Dai; Xiangzhi Zhang; Xiaoyan Wang; Guodong Liu; Qiang Wang; Feng Yu (Human Cell, 2024)

Protein regulator of cytokinesis 1 accentuates cholangiocarcinoma progression via mTORC1-mediated glycolysis - Chao Zhang; Chengkun Qin (Human Cell, 2024)

Tetramerization of pyruvate kinase M2 attenuates graft-versus-host disease by inhibition of Th1 and Th17 differentiation - Meng Wang; Qiu-Jie Li; Hua-Yan Zhao; Jing-Lan Zhang (Human Cell, 2024)

MYCN immunohistochemistry as surrogate marker for MYCN-amplified spinal ependymomas - Divya Mohan; Aruna Nambirajan; Rafat Malik; Agrima Sharma; Vaishali Suri; Kavneet Kaur; Ramesh Doddamani; Ajay Garg; Subhash Gupta; Supriya Mallick; Mehar Chand Sharma (Human Cell, 2024)

Saracatinib prompts hemin-induced K562 erythroid differentiation but suppresses erythropoiesis of hematopoietic stem cells - Lina Ding; Diyu Chen; Yuanshuai Li; Yingjun Xie; Xiaofang Sun; Ding Wang (Human Cell, 2024)
Human myeloid leukemia cells (such as K562) could be used for the study of erythropoiesis, and mature erythroid markers and globins could be induced during leukemia cell differentiation; however, the pathways involved are different compared with those of hematopoietic stem cells (HSCs). We identified the differentially expressed genes (DEGs) of K562 cells and HSCs associated with stem cells and erythroid differentiation. Furthermore, we showed that hemin-induced differentiation of K562 cells could be induced by serum starvation or treatment with the tyrosine kinase inhibitor saracatinib. However, erythroid differentiation of HSCs was inhibited by the deprivation of the important serum component erythropoietin (EPO) or treatment with saracatinib. Finally, we found that the mRNA expression of K562 cells and HSCs was different during saracatinib-treated erythroid differentiation, and the DEGs of K562 cells and HSCs associated with tyrosine-protein kinase were identified. These findings elucidated the cellular phenomenon of saracatinib induction during erythroid differentiation of K562 cells and HSCs, and the potential mechanism is the different mRNA expression profile of tyrosine-protein kinase in K562 cells and HSCs.

RETRACTED ARTICLE: Wnt, notch signaling and exercise: what are their functions? - Yijie Zhao; Guangjun Wang; Zhifeng Wei; Duo Li; Mohammadamin Morshedi (Human Cell, 2024)

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 - SiJun Li; Lingyun Mei; Chufeng He; Xinzhang Cai; Hong Wu; XueWen Wu; Yalan Liu; Yong Feng; Jian Song (Human Cell, 2024)

Establishment and characterization of ZJUCHi003: an induced pluripotent stem cell line from a patient with Temple–Baraitser/Zimmermann–Laband syndrome carrying KCNH1 c.1070G > A (p.R357Q) variant - Die Chen; Jimei Su; Xueying Huang; Hongyu Chen; Tiejia Jiang; Chunchun Zhi; Zuolin Zhou; Bing Zhang; Lan Yu; Xiaoling Jiang (Human Cell, 2024)

Establishment and characterization of NCC-DFSP5-C1: a novel patient-derived dermatofibrosarcoma protuberans cell line - Takuya Ono; Rei Noguchi; Julia Osaki; Taro Akiyama; Yuki Adachi; Naoki Kojima; Yu Toda; Suguru Fukushima; Yuki Yoshimatsu; Akihiko Yoshida; Akira Kawai; Tadashi Kondo (Human Cell, 2024)

Prognostic significance and immune escape implication of tumor-infiltrating neutrophil plasticity in human head and neck squamous cell carcinoma - Xiaoke Zhu; Yu Heng; Duo Zhang; Di Tang; Jian Zhou; Hanqing Lin; Jingyu Ma; Xuping Ding; Lei Tao; Liming Lu (Human Cell, 2024)

Targeting cholesterol biosynthesis for AT/RT: comprehensive expression analysis and validation in newly established AT/RT cell line - Fumitaka Matsumoto; Kiyotaka Yokogami; Ai Yamada; Hiroshi Moritake; Takashi Watanabe; Shinji Yamashita; Yuichiro Sato; Hideo Takeshima (Human Cell, 2024)

Role of mechanically-sensitive cation channels Piezo1 and TRPV4 in trabecular meshwork cell mechanotransduction - Lingling Jing; Kexin Liu; Feng Wang; Ying Su (Human Cell, 2024)

Glycolysis Modulation by METTL7B Shapes Acute Lymphoblastic Leukemia Cell Proliferation and Chemotherapy Response - Li Zhang; Xiao Liu; Shuai Zhou; Peng Wang; Xuan Zhang (Human Cell, 2024)

Establishment and characterization of a novel hypopharyngeal squamous cell carcinoma cell line CZH1 with genetic abnormalities - Jingyu Ma; Xiaoke Zhu; Yu Heng; Xuping Ding; Lei Tao; Liming Lu (Human Cell, 2024)

PDL-1 and insulin resistance in obesity: a possible pathway for macrovascular disease - Mohnad Abdalla; Amr Ahmed El-Arabey; Zhongtao Gai (Human Cell, 2024)

Establishment and characterization of DPC-X4: a novel mixed-type ampullary cancer cell line - Changpeng Chai; Huan Tang; Jianfeng Yi; Lu Li; Cheng Yu; Yuanhui Su; Long Miao; Zhenzhen Ye; Zhengfeng Wang; Wei Luo; Jinjing Hu; Hui Zhang; et al. (Human Cell, 2024)

Correction: Investigation of the mixed origins of the MGC-803 cell line reveals that it is a hybrid cell line derived from HeLa - Meimei Yang; Jing He; Sixuan Xia; Yudong Wang; Jun Xiong; Cong Liao; Nan Li; Sanfu Qu; Chao Shen (Human Cell, 2024)

The miR-3074/BMP7 axis regulates TGF-β-caused activation of hepatic stellate cells in vitro and CCl4-caused murine liver fibrosis in vivo - Bingjie Liu; Xia Xie; Xin Yang; Chengyun Dou; Haibo Tang; Jing Liu (Human Cell, 2024)

A new lymphedema treatment using pyro-drive jet injection - Megumi Nishiyama; Yuko Sakaguchi; Sayuri Morito; Kei Nagase; Takehisa Sakumoto; Kunihiko Yamashita; Mariko Hashiguchi; Makoto Fukuda; Shuji Toda; Shigehisa Aoki (Human Cell, 2024)

Characterization of residual cancer by comparison of a pair of organoids established from a patient with esophageal squamous cell carcinoma before and after neoadjuvant chemotherapy - Takafumi Fuchino; Shusaku Kurogi; Yoshiyuki Tsukamoto; Tomotaka Shibata; Shoichi Fumoto; Hajime Fujishima; Keisuke Kinoshita; Yuka Hirashita; Masahide Fukuda; Chisato Nakada; Yusuke Itai; Kosuke Suzuki; et al. (Human Cell, 2024)

Long noncoding RNA small nucleolar RNA host gene 5 facilitates neuropathic pain in spinal nerve injury by promoting SCN9A expression via CDK9 - Changsheng Wang; Rongsheng Chen; Xitian Zhu; Xiaobo Zhang; Nancheng Lian (Human Cell, 2024)

Research hotspots and emerging trends in mesenchymal stem/stromal cells in bronchopulmonary dysplasia - Meng Ao; Heqian Ma; Meizhen Guo; Xuelin Dai; Xiaoying Zhang (Human Cell, 2023)

Establishment and characterization of NCC-PMP2-C1: a novel patient-derived cell line of pseudomyxoma peritonei with signet ring cells - Rei Noguchi; Yuki Yoshimatsu; Yooksil Sin; Takuya Ono; Ryuto Tsuchiya; Hiroshi Yoshida; Tohru Kiyono; Yutaka Yonemura; Tadashi Kondo (Human Cell, 2023)

Hypothermic machine perfusion reduces donation after circulatory death liver ischemia–reperfusion injury through the SERPINA3-mediated PI3Kδ/Akt pathway - Sheng Peng; Wenjin Liang; Zhongzhong Liu; Shaojun Ye; Zhiyong Peng; Zibiao Zhong; Qifa Ye (Human Cell, 2023)

Generation of iPSC lines (KAIMRCi003A, KAIMRCi003B) from a Saudi patient with Dravet syndrome carrying homozygous mutation in the CPLX1 gene and heterozygous mutation in SCN9A - Maryam Alowaysi; Mohammad Al-Shehri; Amani Badkok; Hanouf Attas; Doaa Aboalola; Moayad Baadhaim; Hajar Alzahrani; Mustafa Daghestani; Asima Zia; Khalid Al-Ghamdi; Asayil Al-Ghamdi; Samer Zakri; et al. (Human Cell, 2023)
The most prevalent form of epileptic encephalopathy is Dravet syndrome (DRVT), which is triggered by the pathogenic variant SCN1A in 80% of cases. iPSCs with different SCN1A mutations have been constructed by several groups to model DRVT syndrome. However, no studies involving DRVT-iPSCs with rare genetic variants have been conducted. Here, we established two DRVT-iPSC lines harboring a homozygous mutation in the CPLX1 gene and heterozygous mutation in SCN9A gene. Therefore, the derivation of these iPSC lines provides a unique cellular platform to dissect the molecular mechanisms underlying the cellular dysfunctions consequent to CPLX1 and SCN9A mutations.

Tissue-specific populations from amniotic fluid-derived mesenchymal stem cells manifest variant in vitro and in vivo properties - Nengqing Liu; Yi Cheng; Ding Wang; Hongmei Guan; Diyu Chen; Juan Zeng; Dian Lu; Yuanshuai Li; Yinghong Yang; Qian Luo; Lifen Zhu; Bin Jiang; et al. (Human Cell, 2023)
Amniotic fluid derived mesenchymal stem cells (AFMSCs), shed along the fetal development, exhibit superior multipotency and immunomodulatory properties compared to MSCs derived from other somatic tissues (e.g., bone marrow and fat). However, AFMSCs display heterogeneity due to source ambiguity, making them an underutilized stem cells source for translational clinical trials. Consequently, there is an urgent need to identify a method to purify the AFMSCs for clinical use. We found that the AFMSCs can be categorized into three distinct groups: kidney-specific AFMSCs (AFMSCs-K), lung-specific AFMSCs (AFMSCs-L), and AFMSCs with an undefined tissue source (AFMSCs-X). This classification was based on tissue-specific gene expression pattern of single cell colony. Additionally, we observed that AFMSCs-X, a minority population within the AFMSCs, exhibited the highest multipotency, proliferation, resistance to senescence and immuno-modulation. Our results showed that AFMSCs-X significantly improved survival rates and reduced bacterial colony forming units (CFU) in cecal ligation and puncture (CLP)-induced septic mice. Therefore, our study introduces a novel classification method to enhance the consistency and efficacy of AFMSCs. These subpopulations, originating from different tissue source, may offer a valuable and innovative resource of cells for regenerative medicine purposes.

Investigation of the mixed origins of the MGC-803 cell line reveals that it is a hybrid cell line derived from HeLa - Meimei Yang; Jing He; Sixuan Xia; Yudong Wang; Jun Xiong; Cong Liao; Nan Li; Sanfu Qu; Chao Shen (Human Cell, 2023)

Establishment and characterization of a patient-derived solitary fibrous tumor/hemangiopericytoma cell line model - Jing Yi Lee; Peiyong Guan; Abner Herbert Lim; Zexi Guo; Zhimei Li; Jessica Sook Ting Kok; Elizabeth Chun Yong Lee; Boon Yee Lim; Bavani Kannan; Jui Wan Loh; Cedric Chuan-Young Ng; Kah Suan Lim; et al. (Human Cell, 2023)

Delivery of microRNA-423-5p by exosome from adipose-derived stem/stromal cells inhibits DVL3 to potentiate autologous fat graft survival through adipogenesis and inflammatory response - Jinglin Zhu; Fangning Zhao; Yimeng Chai; Xinyu Jia; Facheng Li (Human Cell, 2023)

Treatment of type 2 diabetes mellitus with stem cells and antidiabetic drugs: a dualistic and future-focused approach - Priyamvada Amol Arte; Kanchanlata Tungare; Mustansir Bhori; Renitta Jobby; Jyotirmoi Aich (Human Cell, 2023)

Estrogen receptor- and progesterone receptor-positive breast tumors have higher mRNA levels of NR3C1 and ZBTB16, with implications in prognosis for luminal A subtype - Caglar Berkel (Human Cell, 2023)

LINC00941: a novel player involved in the progression of human cancers - Qibin Yan; Xinming Su; Yunzhu Chen; Zehua Wang; Wenbo Han; Qing Xia; Yunan Mao; Jiahua Si; Hanbing Li; Shiwei Duan (Human Cell, 2023)

Nucleoporin 93, a new substrate of the E3 ubiquitin protein ligase HECTD1, promotes esophageal squamous cell carcinoma progression - Jinfeng Zhang; Yanzhong Xin; Xiaodong Ling; Hao Liang; Luquan Zhang; Chengyuan Fang; Jianqun Ma (Human Cell, 2023)

Hypoxia and interleukin-1-primed mesenchymal stem/stromal cells as novel therapy for stroke - Maryam Adenike Salaudeen; Stuart Allan; Emmanuel Pinteaux (Human Cell, 2023)
Promising preclinical stroke research has not yielded meaningful and significant success in clinical trials. This lack of success has prompted the need for refinement of preclinical studies with the intent to optimize the chances of clinical success. Regenerative medicine, especially using mesenchymal stem/stromal cells (MSCs), has gained popularity in the last decade for treating many disorders, including central nervous system (CNS), such as stroke. In addition to less stringent ethical constraints, the ample availability of MSCs also makes them an attractive alternative to totipotent and other pluripotent stem cells. The ability of MSCs to differentiate into neurons and other brain parenchymal and immune cells makes them a promising therapy for stroke. However, these cells also have some drawbacks that, if not addressed, will render MSCs unfit for treating ischaemic stroke. In this review, we highlighted the molecular and cellular changes that occur following an ischaemic stroke (IS) incidence and discussed the physiological properties of MSCs suitable for tackling these changes. We also went further to discuss the major drawbacks of utilizing MSCs in IS and how adequate priming using both hypoxia and interleukin-1 can optimize the beneficial properties of MSCs while eliminating these drawbacks.

Cell replacement therapy with stem cells in multiple sclerosis, a systematic review - Maria Veatriki Christodoulou; Ermioni Petkou; Natalia Atzemoglou; Eleni Gkorla; Aikaterini Karamitrou; Yannis V. Simos; Stefanos Bellos; Chryssa Bekiari; Panos Kouklis; Spyridon Konitsiotis; Patra Vezyraki; Dimitrios Peschos; et al. (Human Cell, 2023)
Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and neurodegenerative disease of the central nervous system (CNS), characterized by demyelination and axonal loss. It is induced by attack of autoreactive lymphocytes on the myelin sheath and endogenous remyelination failure, eventually leading to accumulation of neurological disability. Disease-modifying agents can successfully address inflammatory relapses, but have low efficacy in progressive forms of MS, and cannot stop the progressive neurodegenerative process. Thus, the stem cell replacement therapy approach, which aims to overcome CNS cell loss and remyelination failure, is considered a promising alternative treatment. Although the mechanisms behind the beneficial effects of stem cell transplantation are not yet fully understood, neurotrophic support, immunomodulation, and cell replacement appear to play an important role, leading to a multifaceted fight against the pathology of the disease. The present systematic review is focusing on the efficacy of stem cells to migrate at the lesion sites of the CNS and develop functional oligodendrocytes remyelinating axons. While most studies confirm the improvement of neurological deficits after the administration of different stem cell types, many critical issues need to be clarified before they can be efficiently introduced into clinical practice.

Erythropoietin improves pulmonary hypertension by promoting the homing and differentiation of bone marrow mesenchymal stem cells in lung tissue - Zhendong Zhong; Kang Li; Chongyang Shen; Yuxiao Ma; Lu Guo (Human Cell, 2023)

Establishment and characterization of a novel hilar cholangiocarcinoma cell line, CBC3T-1 - Mingzhen Bai; Ningzu Jiang; Wenkang Fu; Chongfei Huang; Liang Tian; Ningning Mi; Long Gao; Haidong Ma; Yawen Lu; Jie Cao; Chao Zhang; Ping Yue; et al. (Human Cell, 2023)
Cholangiocarcinoma (CCA) is a group of malignant heterogeneous cancer arising from the biliary tree. The tumor is characterized by insidious onset, high degree of malignancy, poor prognosis, and high recurrence rate. Immortalized cancer cell lines are the best and easiest models for in vitro cancer research. Here, we established a naturally immortalized highly tumorigenic hilar cholangiocarcinoma (hCCA) cell line, CBC3T-1. The CBC3T-1 cell line was cultured for over 60 passages. Thorough analysis showed that CBC3T-1 cells share characteristics similar to original tumor cells from patients with cholangiocarcinoma and display a stable phenotype, including features of epithelial origin, stem cell-like properties, as well as a high invasive and migratory capability and tumorigenicity in mice. Furthermore, this cell line showed the best sensitivity to paclitaxel, followed by gemcitabine. RNA sequencing and whole‑exome sequencing showed that cancer-associated pathways and somatic mutations played a dominant role in the development of CCA. We established and characterized a new hCCA cell line, CBC3T-1, which contributes to a better understanding of bile duct cancer, and can be used to study tumorigenesis and progression and the role of anticancer drugs.

Human dental pulp stem cells have comparable abilities to umbilical cord mesenchymal stem/stromal cells in regulating inflammation and ameliorating hepatic fibrosis - Peixing Chen; Yanchun Lin; Wenbo Lin; Yun Li; Ting Fu; Yuanyue Liu; Tian Guan; Man Xin; Ling Ye; Peiluan Wang; Haoyu Zeng; Kaitao Yao (Human Cell, 2023)

Establishment and functional testing of a novel ex vivo extraskeletal osteosarcoma cell model (USZ20-ESOS1) - Kim Harnisch; Sabrina Steiner; Alicia Pliego-Mendieta; Yanjiang Chen; Lara Planas-Paz; Chantal Pauli (Human Cell, 2023)
Extraskeletal osteosarcoma (ESOS) is a rare malignant mesenchymal tumor that originates in the soft tissue. ESOS accounts for less than 1% of all soft tissue sarcomas and exhibits an aggressive behavior with a high propensity for local recurrence and distant metastasis. Despite advances in treatment, the prognosis for ESOS remains poor, with a five-year survival rate of less than 50% and 27% for metastatic patients. Ex vivo models derived from patient samples are critical tools for studying rare diseases with poor prognoses, such as ESOS, and identifying potential new treatment strategies. In this work, we established a novel ESOS ex vivo sarco-sphere model from a metastatic lesion to the dermis for research and functional testing purposes. The ex vivo cell model accurately recapitulated the native tumor, as evidenced by histomorphology and molecular profiles. Through a functional screening approach, we were able to identify novel individual anti-cancer drug sensitivities for different drugs such as romidepsin, miverbresib and to multiple kinase inhibitors. Overall, our new ESOS ex vivo cell model represents a valuable tool for investigating disease mechanisms and answering basic and translational research questions.

Establishment and characterization of a recurrent malignant peripheral nerve sheath tumor cell line: RsNF - Xingnan Zhang; Chenhao Hu; Dezhi Li; Song Liu (Human Cell, 2023)

Autophagy induced by Helicobacter Pylori infection can lead to gastric cancer dormancy, metastasis, and recurrence: new insights - Abdullatif Akbari; Seyed Mostafa Noorbakhsh Varnosfaderani; Melika Sadat Haeri; Zeinab Fathi; Fatemeh Aziziyan; Ali Yousefi Rad; Hamidreza Zalpoor; Mohsen Nabi-Afjadi; Yalda Malekzadegan (Human Cell, 2023)

Receptor tyrosine kinase gene expression profiling of orbital rhabdomyosarcoma unveils MET as a potential biomarker and therapeutic target - Sheetal Chauhan; Seema Sen; Khushboo Irshad; Seema Kashyap; Neelam Pushker; Rachna Meel; Mehar Chand Sharma (Human Cell, 2023)

Establishment and characterization of NCC-LMS3-C1: a novel patient-derived cell line of leiomyosarcoma - Yuki Yoshimatsu; Rei Noguchi; Julia Osaki; Yooksil Sin; Ryuto Tsuchiya; Takuya Ono; Taro Akiyama; Yuki Adachi; Yoshikazu Tanzawa; Akihiko Yoshida; Akira Kawai; Tadashi Kondo (Human Cell, 2023)

Tracking circulating PD-L1-positive cells to monitor the outcome of patients with gastric cancer receiving anti-HER2 plus anti-PD-1 therapy - Xiaoyi Chong; Yanyan Li; Jialin Lu; Xujiao Feng; Yilin Li; Xiaotian Zhang (Human Cell, 2023)
Dual blockade of HER2 and PD-1/PD-L1 is the most promising regimen for HER2-positive patients with gastric cancer (GC); PD-L1 combined positive score, rather than HER2 status, indicates potential benefit. Circulating tumor cells (CTCs) and circulating endothelial cells (CECs) derived from the tumor microenvironment provide platforms for the dynamic evaluation of PD-L1 expression. Whether PD-L1 positive CTCs/CECs (PD-L1 + CTCs/CECs) can serve as biomarkers for evaluating the efficacy of combination therapy remains unknown. Therefore, this study investigated PD-L1 expression and heterogeneous karyotypic features of CTCs/CECs and their involvement in the clinical response to treatment in 72 patients with advanced GC by applying a pre-established surface molecule-independent subtraction enrichment (SE)-iFISH strategy. In the captured PD-L1 positive cells, there were 42.80% and 57.20% of CTCs and CECs, respectively. PD-L1 + CTCs were pre-therapeutically detected in 0% (0/11) of HER2-negative patients and 14.75% (9/61) of HER2-positive patients. The presence of baseline PD-L1 + CTCs was relevant to inferior prognosis (mPFS: 14.40 months vs 5.00 months, P = 0.065); post-treatment PD-L1 + CECs were associated with longer irPFS (immunotherapeutic-related PFS) (mPFS: 15.57 months vs 6.73 months, P = 0.053). Further dynamic karyotype-based profiling of PD-L1 + CTCs/CECs indicated that multiploidy and triploidy were the dominant subtypes of baseline PD-L1 + CTCs, and that triploidy was specifically associated with therapeutic resistance. Intratherapeutically detected multiploid PD-L1 + CECs demonstrated a superior clinical response; triploidy and tetraploidy contributed to acquired resistance. The karyotypic features of PD-L1 + CTCs/CECs should be dynamically profiled in patients with GC treated with anti-HER2 plus anti-PD-1 therapy. Triploid-PD-L1 + CTCs and multiploid-PD-L1 + CECs are potential indicators of therapeutic response.

Passaging of gingival fibroblasts from periodontally healthy and diseased sites upregulates osteogenesis-related genes - Gerasimos D. Karlis; Ton Schoenmaker; Nektarios Tsoromokos; Olaf E. Veth; Bruno G. Loos; Teun J. de Vries (Human Cell, 2023)
To investigate biological processes of the periodontium, in vitro primary cell models have been established. To study the biology of the gingiva, primary gingival fibroblast cell models are widely used. For such experiments, cells need to be expanded and passaged. A key assumption is that primary cells maintain most of their original characteristics they have in situ. The aim of this research is to explore the impact of early passaging on selected gene expression of human gingival fibroblast cells. For this purpose, gene expression from the outgrowth of the resected tissues until the fourth passage was followed for nine tissue samples, from both healthy and diseased sites. Micrographs were taken from the cultures, RNA was extracted from the samples of each passage and quantitative PCR was performed for selected genes representing various biological processes. Epithelial cells were present during the first outgrowth, but were no longer present in the second passage. Our results indicate that the morphology of the gingival fibroblast cells does not change with passaging and that passages 2–4 contain only gingival fibroblasts. Gene expression of M-CSF , TNF-α , TLR4 , POSTN and FAPα was unchanged by passaging, the expression of IL-6 , IL-1β and TLR2 decreased due to passaging and the expression of in particular the selected osteogenesis genes ( ALP , RUNX2 , Osteonectin , COL1A ), OPG and MKI67 increased with passaging. Worldwide, use of the same passage in laboratory experiments using primary cell cultures is the standard. Our results support this, since for certain genes, in particular osteogenesis genes, expression may alter solely due to passaging.

Prospects of plant-derived exosome-like nanocarriers in oncology and tissue engineering - Shima Rahmati; Hafez Karimi; Morteza Alizadeh; Amir Hossein Khazaei; Ana Cláudia Paiva-Santos; Leila Rezakhani; Esmaeel Sharifi (Human Cell, 2023)

Targeting circulating tumor cells to prevent metastases - Karol Gostomczyk; Mohammed Dheyaa Marsool Marsool; Hamnah Tayyab; Anju Pandey; Jędrzej Borowczak; Facundo Macome; Jose Chacon; Tirth Dave; Mateusz Maniewski; Łukasz Szylberg (Human Cell, 2023)
Circulating tumor cells (CTCs) are cancer cells that detach from the primary tumor, enter the bloodstream or body fluids, and spread to other body parts, leading to metastasis. Their presence and characteristics have been linked to cancer progression and poor prognosis in different types of cancer. Analyzing CTCs can offer valuable information about tumors’ genetic and molecular diversity, which is crucial for personalized therapy. Epithelial-mesenchymal transition (EMT) and the reverse process, mesenchymal-epithelial transition (MET), play a significant role in generating and disseminating CTCs. Certain proteins, such as EpCAM, vimentin, CD44, and TGM2, are vital in regulating EMT and MET and could be potential targets for therapies to prevent metastasis and serve as detection markers. Several devices, methods, and protocols have been developed for detecting CTCs with various applications. CTCs interact with different components of the tumor microenvironment. The interactions between CTCs and tumor-associated macrophages promote local inflammation and allow the cancer cells to evade the immune system, facilitating their attachment and invasion of distant metastatic sites. Consequently, targeting and eliminating CTCs hold promise in preventing metastasis and improving patient outcomes. Various approaches are being explored to reduce the volume of CTCs. By investigating and discussing targeted therapies, new insights can be gained into their potential effectiveness in inhibiting the spread of CTCs and thereby reducing metastasis. The development of such treatments offers great potential for enhancing patient outcomes and halting disease progression.

Therapeutic potential of miRNAs in placental extracellular vesicles in ovarian and endometrial cancer - Yi Zhang; Yunhui Tang; Xinyue Chen; Xinyi Sun; Min Zhao; Qi Chen (Human Cell, 2023)

Activation of cell adhesion and migration is an early event of platelet-rich plasma (PRP)-dependent stimulation of human adipose-derived stem/stromal cells - Michika Fukui; Fangyuan Lai; Masakatsu Hihara; Toshihito Mitsui; Yuki Matsuoka; Zhongxin Sun; Sakurako Kunieda; Shigeru Taketani; Tokifumi Odaka; Kazu Okuma; Natsuko Kakudo (Human Cell, 2023)

MicroRNA-10a-5p-mediated downregulation of GATA6 inhibits tumor progression in ovarian cancer - Feiying Gao; Qiang Wu; Dan Lu (Human Cell, 2023)

Isolation of tumor stem-like cells from primary laryngeal squamous cell carcinoma cells (FD-LS-6) - Duo Zhang; Di Tang; Pen-tao Liu; Lei Tao; Li-ming Lu (Human Cell, 2023)

Copper in Cancer: from transition metal to potential target - Can Fang; Zhiwei Peng; Yaru Sang; Zihao Ren; Huiming Ding; Haibo Yuan; Kongwang Hu (Human Cell, 2023)

The effect of SARS-CoV-2 on the development of Parkinson's disease: the role of α-synuclein - Farideh Iravanpour; Majid Reza Farrokhi; Morteza Jafarinia; Razieh Tavakoli Oliaee (Human Cell, 2023)

TRIM28 recruits E2F1 to regulate CBX8-mediated cell proliferation and tumor metastasis of ovarian cancer - Fubin Zhang; Tianhong Zhu; Chenghao Wu; Dongsheng Shen; Lixiao Liu; Xueqin Chen; Yutao Guan; Huiqing Ding; Xiaowen Tong (Human Cell, 2023)

A short-term three dimensional culture-based drug sensitivity test is feasible for malignant bone tumors - Hiroaki Goto; Takashi Ohtsu; Mieko Ito; Maiko Sagisaka; Takuya Naruto; Jun-ichi Nagai; Norihiko Kitagawa; Mio Tanaka; Masakatsu Yanagimachi; Yukihiko Hiroshima; Yohei Miyagi (Human Cell, 2023)

Establishment and characterization of BMC-PDC-019: a novel patient-derived cell line of EGFR-mutant pulmonary adenocarcinoma transformed into small-cell lung cancer - Mi Young Kim; Seung Yeon Jung; Sungyoul Hong; So Won Oh; Kwang Nam Jin; Ji Eun Kim; Jin-Soo Kim (Human Cell, 2023)

Specific downregulation of microRNA-186 induces neural stem cell self-renewal by upregulating Bmi-1/FoxG1 expression - Tuantuan Chen; Jing Liu; Yang Liu; Yang Chen; Xue Wang (Human Cell, 2023)

Remodeling periodontal osteoimmune microenvironment through MAPK/NFκB phosphorylation pathway of macrophage via intelligent ROS scavenging - Xinyi Qiu; Haoran Peng; Yue Zhao; Yijun Yu; Jie Yang; Chao Liu; Shuangshuang Ren; Leiying Miao (Human Cell, 2023)

Generation of an induced pluripotent stem cell line from a patient with epileptic encephalopathy caused by the CYFIP2 R87C variant - Isabelle Leticia Zaboroski Silva; Rubens Gomes-Júnior; Evelin Brandão da Silva; Isadora May Vaz; Valderez Ravaglio Jamur; Bruno Solano de Freitas Souza; Patrícia Shigunov (Human Cell, 2023)

The role of mitochondrial/metabolic axis in development of tamoxifen resistance in breast cancer - Hany N. Azzam; Marwa O. El-Derany; Sara A. Wahdan; Reham M. Faheim; Gouda K. Helal; Ebtehal El-Demerdash (Human Cell, 2023)
Only a few investigations, to our knowledge, have examined the bioenergetics of Tamoxifen (TMX) resistant individuals and reported altered mitochondrial activity and metabolic profile. The primary cause of TMX resistance is firmly suggested to be metabolic changes. Metabolic variations and hypoxia have also been linked in a bidirectional manner. Increased hypoxic levels correlate with early recurrence and proliferation and have a negative therapeutic impact on breast cancer (BC) patients. Hypoxia, carcinogenesis, and patient death are all correlated, resulting in more aggressive traits, a higher chance of metastasis, and TMX resistance. Consequently, we sought to investigate the possible role of the metabolic/hypoxial axis Long non-coding RNA (LncRNA) Taurine up-regulated 1 (TUG-1), Micro-RNA 186-5p (miR-186), Sirtuin-3 (SIRT3), Peroxisome Proliferator Activator Receptor alpha (PPAR-α), and Hypoxia-Inducible Factor-1 (HIF-1) in the development of TMX resistance in BC patients and to correlate this axis with tumor progression. Interestingly, this will be the first time to explore epigenetic regulation of this axis in BC.

The induction of ferroptosis by KLF11/NCOA4 axis: the inhibitory role in clear cell renal cell carcinoma - Zi-Qi Zhou; Xi Lv; Shi-Bo Liu; Hong-Chen Qu; Qing-Peng Xie; Long-Feng Sun; Gang Li (Human Cell, 2023)

Circ-SFMBT2 sponges miR-224-5p to induce ketamine-induced cystitis by up-regulating metadherin (MTDH) - Fanchang Zeng; Qinghui Wu; Mi Song; Xinli Kang; Zhewen Ou; Zuobing Yang; Liumei Luo; Daoyuan Li (Human Cell, 2023)

De-differentiation in cultures of organoids from luminal-type breast cancer is restored by inhibition of NOTCH signaling - Hiroyuki Uematsu; Chieko Saito; Jumpei Kondo; Kunishige Onuma; Roberto Coppo; Yukiko Mori; Manabu Muto; Yuichiro Kikawa; Manami Tada; Tomoharu Sugie; Masahiro Inoue (Human Cell, 2023)

M1 linear ubiquitination of LKB1 inhibits vascular endothelial cell injury in atherosclerosis through activation of AMPK - Haiquan Huangfu; Zhichao Huang; Weiqian Liao; Tianyu Zou; Xiaoming Shang; Hairui Yu (Human Cell, 2023)

The interferon-stimulated genes are plausibly a primary genetic locus for genetically enabling hyperinflammatory and autoimmune diseases and lymphocyte exhaustion - Kevin Roe (Human Cell, 2023)

CTLA-4 and ovarian cancer residual tumors: the dark side of debulking surgery - Mohnad Abdalla; Amr Ahmed El-Arabey; Zhongtao Gai (Human Cell, 2023)

Multi-omic profiling and real time ex vivo modelling of imatinib-resistant dermatofibrosarcoma protuberans with fibrosarcomatous transformation - Jason Yongsheng Chan; Elizabeth Chun Yong Lee; Zhimei Li; Jing Yi Lee; Abner Herbert Lim; Eileen Poon (Human Cell, 2023)

Identification of a gene set that maintains tumorigenicity of the hepatocellular carcinoma cell line Li-7 - Yusuke Seyama; Kazuhiro Sudo; Suguru Hirose; Yukako Hamano; Takeshi Yamada; Takashi Hiroyama; Ryosuke Sasaki; Masami Yokota Hirai; Ichinosuke Hyodo; Kiichiro Tsuchiya; Yukio Nakamura (Human Cell, 2023)
The identification and development of therapeutic targets in cancer stem cells that lead to tumor development, recurrence, metastasis, and drug resistance is an important goal in cancer research. The hepatocellular carcinoma cell line Li-7 contains functionally different types of cells. Cells with tumor-forming activity are enriched in cancer stem cell-like CD13 + CD166 − cells and this cell population gradually decreases during culture in conventional culture medium (RPMI1640 containing 10% fetal bovine serum). When Li-7 cells are cultured in mTeSR1, a medium developed for human pluripotent stem cells, CD13 + CD166 − cells, and their tumorigenicity is maintained. Here, we sought to identify the mechanisms of tumorigenicity in this sub-population. We compared gene expression profiles of CD13 + CD166 − cells with other cell sub-populations and identified nine overexpressed genes ( ENPP2 , SCGN , FGFR4 , MCOLN3 , KCNJ16 , SMIM22 , SMIM24 , SERPINH1 , and TMPRSS2 ) in CD13 + CD166 − cells. After transfer from mTeSR1 to RPMI1640 containing 10% fetal bovine serum, the expression of these nine genes decreased in Li-7 cells and they lost tumorigenicity. In contrast, when these genes of Li-7 cells were forcibly expressed in cultures using RPMI1640 containing 10% fetal bovine serum, Li-7 cells maintained tumorigenicity. A metabolome analysis using capillary electrophoresis–mass spectrometry showed that two metabolic pathways, “Alanine, aspartate and glutamate metabolism” and “Arginine biosynthesis” were activated in cancer stem-cell-like cells. Our analyses here showed potential therapeutic target genes and metabolites for treatment of cancer stem cells in hepatocellular carcinoma.

Probe-based confocal laser endomicroscopy for real-time evaluation of colorectal liver metastasis in resected surgical specimens - Mikiya Takao; Yoshikuni Kawaguchi; Masaru Matsumura; Yusuke Kazami; Meguri Tanimoto; Satoru Abe; Harufumi Maki; Takeaki Ishizawa; Junichi Arita; Nobuhisa Akamatsu; Junichi Kaneko; Norihiro Kokudo; et al. (Human Cell, 2023)
Probe-based confocal laser endomicroscopy (pCLE) enables real-time examination of tissue structure. This study investigated pCLE with or without fluorescein sodium for the intraoperative diagnosis of colorectal liver metastasis (CLM) and detection of surgical margins. Thirty-four specimens of CLM and adjacent noncancerous tissue were obtained from 21 patients and examined by pCLE between May 2017 and March 2018. Images were obtained both without and with fluorescein sodium applied to the cut surface and compared with hematoxylin and eosin-stained tissue. Fluorescence intensity (FI) was measured by luminance-analysis software. Without external fluorophores, pCLE visualized 91.2% of CLM tissues as an irregular structure with low autofluorescence and 90.5% of noncancerous liver tissues as a regular structure with high autofluorescence. The median FI was significantly lower in cancer than in benign tissue in patients without chemotherapy [70.4 (51.6–110) vs. 48.3 (39.0–59.4), p = 0.002] and with chemotherapy [67.9 (54.6–89.2) vs. 48.6 (28.8–82.1), p < 0.001]. The border was clearly visible; pCLE with fluorescein sodium clearly showed their morphologies. In summary, our study demonstrated real-time pCLE distinguished CLM and noncancerous tissue by differences in structure and FI regardless of prehepatectomy chemotherapy. Fluorescein spray facilitated clear visualization of differences in the morphology.

The role of exosomes and their enhancement strategies in the treatment of osteoarthritis - Linzhen Huang; Ge Dong; Jie Peng; Ting Li; Mi Zou; Kaibo Hu; Yuan Shu; Tao Cheng; Liang Hao (Human Cell, 2023)

Establishment and characterization of CSCRi006-A: an induced pluripotent stem cell line generated from a patient with Diamond-Blackfan Anemia (DBA) carrying ribosomal protein S19 (RPS19) mutation - Sonam Rani; Vasanth Thamodaran; Krittika Nandy; N. A. Fouzia; Madhavi Maddali; Praveena Rajesh; S. Vijayanand; Ernest David; Shaji R. Velayudhan (Human Cell, 2023)

Comprehensive cell surface protein profiling of human mesenchymal stromal cells from peritoneal dialysis effluent and comparison with those from human bone marrow and adipose tissue - Ganggang Shi; Chong Yang; Lan Zhou; Ming Zong; Qiunong Guan; Gerald da Roza; Hao Wang; Hualin Qi; Caigan Du (Human Cell, 2023)
Peritoneal mesenchymal stromal cells (pMSCs) are isolated from peritoneal dialysis (PD) effluent, and treatment with the pMSCs reduces peritoneal membrane injury in rat model of PD. This study was designed to verify the identity of the pMSCs. pMSCs were grown in plastic dishes for 4–7 passages, and their cell surface phenotype was examined by staining with a panel of 242 antibodies. The positive stain of each target protein was determined by an increase in fluorescence intensity as compared with isotype controls in flow cytometrical analysis. Here, we showed that pMSCs predominantly expressed CD9, CD26, CD29, CD42a, CD44, CD46, CD47, CD49b, CD49c, CD49e, CD54, CD55, CD57, CD59, CD63, CD71, CD73, CD81, CD90, CD98, CD147, CD151, CD200, CD201, β2-micoglobulin, epithelial growth factor receptor, human leukocyte antigen (HLA) class 1, and, to a lesser extent, CD31, CD45RO, CD49a, CD49f, CD50, CD58, CD61, CD105, CD164, and CD166. These cells lacked expression of most hematopoietic markers such as CD11b, CD14, CD19, CD34, CD40, CD80, CD79, CD86, and HLA-DR. There was 38.55% difference in the expression of 83 surface proteins between bone marrow (BM)-derived MSCs and pMSCs, and 14.1% in the expression of 242 proteins between adipose tissue (AT)-derived MSCs and pMSCs. The BM-MSCs but not both AT-MSCs and pMSCs express cytokine receptors (IFNγR, TNFI/IIR, IL-1R, IL-4R, IL-6R, and IL-7R). In conclusion, pMSCs exhibited a typical cell surface phenotype of MSCs, which was not the same as on BM-MSCs or AT-MSCs, suggesting that the pMSCs may represent a different MSC lineage from peritoneal cavity.

Circ_0067934: a circular RNA with roles in human cancer - Liqing Yu; Jiacheng Zheng; Jiali Yu; Yujun Zhang; Huoli Hu (Human Cell, 2023)
A circular RNA (circRNA) is a non-coding RNA (ncRNA) derived from reverse splicing from pre-mRNA and is characterized by the absence of a cap structure at the 5′ end and a poly-adenylated tail at the 3′ end. Owing to the development of RNA sequencing and bioinformatics approaches in recent years, the important clinical value of circRNAs has been increasingly revealed. Circ_0067934 is an RNA molecule of 170 nucleotides located on chromosome 3q26.2. Circ_0067934 is formed via the reverse splicing of exons 15 and 16 in PRKCI (protein kinase C Iota). Recent studies revealed the upregulation or downregulation of circ_0067934 in various tumors. The expression of circ_0067934 was found to be correlated with tumor size, TNM stage, and poor prognosis. Based on experiments with cancer cells, circ_0067934 promotes cancer cell proliferation, migratory activity, and invasion when overexpressed or downregulated. The potential mechanism involves the binding of circ_0067934 to microRNAs (miRNAs; miR-545, miR-1304, miR-1301-3p, miR-1182, miR-7, and miR-1324) to regulate the post-transcriptional expression of genes. Other mechanisms include inhibition of the Wnt/β-catenin and PI3K/AKT signaling pathways. Here, we summarized the biological functions and possible mechanisms of circ_0067934 in different tumors to enable further exploration of its translational applications in clinical diagnosis, therapy, and prognostic assessments.

The effect of local anaesthetics on apoptosis and NETosis of human neutrophils in vitro: comparison between lidocaine and ropivacaine - Karolina Iwona Kulińska; Sandra Szałkowska; Mirosław Andrusiewicz; Małgorzata Kotwicka; Hanna Billert (Human Cell, 2023)
There are immunological consequences to the method by which neutrophils undergo cell death. Neutrophil apoptosis, called silent death, leads to the resolution of inflammation, while NETosis deepens and prolongs the inflammatory response and is associated with a worse prognosis of severe infections, e.g., sepsis. Besides nociceptive inhibition, local anaesthetics modulate leukocyte functions, even at low, clinically relevant concentrations. There is currently no data on ropivacaine NETosis, and this study aimed to evaluate the impact of clinical concentrations of ropivacaine (0.0007, 0.007 and 1.4 mmol/L) and lidocaine (0.002, 0.02 and 4 mmol/L) on apoptosis and NETosis of adult peripheral blood neutrophils after 2 h of incubation. Neutrophil identification, apoptosis and NETosis were evaluated by flow cytometry using forward and side scatter characteristics and fluorescent labelling: CD15 for neutrophils identification; Annexin V and propidium iodide for apoptosis and citrullinated histone H3 and myeloperoxidase for NETosis. Lidocaine (4 mmol/L) and ropivacaine (1.4 mmol/L) induced early apoptosis in resting but not in stimulated neutrophils. Low doses of ropivacaine (0.0007 and 0.007 mmol/L) decreased the number of late apoptotic neutrophils, and the lowest dose slightly increased their viability. None of the drugs induced NETosis in resting neutrophils but decreased NETosis at clinical concentrations compared to PMA-stimulated 4 mM lidocaine, PMA-stimulated control, and 1.4 mM ropivacaine. The effect of lidocaine and ropivacaine on apoptosis and NETosis depended on neutrophil stimulation and drug concentrations. Ropivacaine tends to be cytoprotective at concentrations observed in plasma under local anaesthesia. Lidocaine enhanced NETosis at high concentration only in stimulated neutrophils. Thus, both drugs have the ability to change the course of inflammation.

PIAS1 impedes vascular endothelial injury and atherosclerotic plaque formation in diabetes by blocking the RUNX3/TSP-1 axis - Qingsong Jin; Tiantian Zhao; Liangyan Lin; Xiaoyan Yao; Yaqin Teng; Dongdong Zhang; Yongjun Jin; Meizi Yang (Human Cell, 2023)

tRNAThr-miR-720 mimicry in glioma cells - Guillermo Aquino-Jarquin (Human Cell, 2023)

Long noncoding RNA XLOC_006786 inhibits the proliferation, invasion and metastasis of osteosarcoma cells through NOTCH3 signaling pathway by targeting miR-491-5p - Jia-Yi Xu; Yang-fan Lv; Ya Cao; Hong-min Ma; Xiang-lin Hao; Lu Huang; Xue-feng Tang; Qiao-nan Guo (Human Cell, 2023)

Cofilin-1 induces acute kidney injury via the promotion of endoplasmic reticulum stress-mediated ferroptosis - Sihao Lin; Jie Wang; Bin Cao; Yang Huang; Xujun Sheng; Yingjian Zhu (Human Cell, 2023)
Ischemia–reperfusion injury (IRI) leads to acute kidney injury (AKI), which poses serious threat to public health and society. Many clinical studies were conducted to evaluate several biomarkers in AKI, among which Cofilin-1 remains to be a very promising one. To explore the potential mechanism of Cofilin-1 in AKI, we established an oxygen-glucose-deprivation (OGD)-induced AKI cell model. The overexpression and knock-down Cofilin-1 were used for gain- and loss-of-function. Pharmacological inhibitors were employed to study the related pathways. The results showed that Cofilin-1 was significantly upregulated in AKI cells, knocking down Cofilin-1 protected cells against the effect of OGD treatment and alleviated AKI phenotypes. Overexpression of Cofilin-1 might induce AKI by triggering ferroptosis, inhibiting NF-κB signaling or ER stress pathway attenuated Cofilin-1 induced lipid peroxidation and AKI. We also validated our findings in IRI-induced AKI mouse models in vivo. Our work elucidated that Cofilin-1 might induce AKI via promoting ER stress-mediated ferroptosis and argues it as a biomarker for early diagnosis of AKI. We also expect to offer novel insights on future therapeutic interventions.

Two-carba cyclic phosphatidic acid treatment promotes phenotypic switch from M1 to M2 microglia and prevents behavioral abnormalities in a mouse model of neuropsychiatric systemic lupus erythematosus - Wataru Nagata; Mari Gotoh; Akiho Koizumi; Keiko Fukasawa; Keiichi Nakagawa; Yasushi Satoh; Toshiaki Ishizuka (Human Cell, 2023)

F-box and leucine-rich repeat protein 16 controls tamoxifen sensitivity via regulation of mitochondrial respiration in estrogen receptor-positive breast cancer cells - Feng Chen; Lu Wang; Yanrong Feng; Wenxin Ma; Junqin Liu; Qianyao Bi; Yao Song; Rui Gao; Yanhan Jia (Human Cell, 2023)

Establishment and characterization of a novel cell line (SCCOHT-CH-1) and PDX models derived from Chinese patients of small cell ovarian carcinoma of the hypercalcemic type - Yi Gao; Kewei Zheng; Mingyi Kang; Jing Xu; Yan Ning; Weiguo Hu; Ke Li; Yu Kang; Congjian Xu (Human Cell, 2023)
Small cell carcinoma of the ovary hypercalcemic type (SCCOHT) is a rare and aggressive malignancy that poses a significant clinical challenge due to its grim prognosis. Unfortunately, only three SCCOHT cell lines are currently available for scientific research. In this study, we have successfully established a novel SCCOHT cell line from a recurrent lesion of a SCCOHT patient, named SCCOHT-CH-1. We comprehensively characterized the novel cell line by employing techniques such as morphological observation, CCK-8 assay, Transwell assay, clone formation assay, short tandem repeat sequence (STR) analysis, karyotype analysis, immunohistochemical staining, western blot assay, and xenograft tumor formation assay. SCCOHT-CH-1 cells were small circular and had a unique STR profile. The population-doubling time of SCCOHT-CH-1 was 33.02 h. The cell line showed potential migratory and invasive ability. Compared with another SCCOHT cell line COV434, SCCOHT-CH-1 exhibited higher expression of AKT, VIM, and CCND1. At the same time, SCCOHT-CH-1 has the ability of tumorigenesis in vivo. We also successfully constructed three patient-derived xenograft (PDX) models of SCCOHT, which were pathologically diagnosed to be consistent with the primary tumor, accompanied by loss of SAMRCA4 protein expression. The establishment of SCCOHT-CH-1 cell line and PDX models from Chinese people represent a pivotal step toward unraveling the molecular mechanism of SCCOHT and fostering the development of targeted interventions to tackle this challenging malignancy.

Adenosine metabolism by mesenchymal stromal cells isolated from different human tissues - Bruna Campos Galgaro; Liziane Raquel Beckenkamp; Liliana I. Sous Naasani; Márcia Rosângela Wink (Human Cell, 2023)

Intermittent cyclic mechanical compression promotes endplate chondrocytes degeneration by disturbing Nrf2/PINK1 signaling pathway-dependent mitophagy - Quan Zheng; Chuan-dong Wang; Song Shao; Ming-fan Wu; Qiang-bing Dou; Qi-wei Wang; Liang-ye Sun (Human Cell, 2023)

The potential role of acid ceramidase in oral squamous cell carcinoma chemo-resistance by inducing autophagy - Ali Norouzi; Fatemeh Davodabadi; Seyed Mostafa Noorbakhsh Varnosfaderani; Hamidreza Zalpoor (Human Cell, 2023)

RNA methylation reading protein YTHDF2 relieves myocardial ischemia–reperfusion injury by downregulating BNIP3 via m6A modification - Xinyong Cai; Pengtao Zou; Lang Hong; Yanmei Chen; Yuliang Zhan; Yuanyuan Liu; Liang Shao (Human Cell, 2023)

Establishment and characterization of NCC-DFSP4-C1: a novel cell line from a patient with dermatofibrosarcoma protuberans having the fibrosarcomatous transformation - Taro Akiyama; Yuki Yoshimatsu; Rei Noguchi; Yooksil Sin; Julia Osaki; Takuya Ono; Yuki Adachi; Ryuto Tsuchiya; Yu Toda; Koichi Ogura; Naoki Kojima; Akihiko Yoshida; et al. (Human Cell, 2023)

The miR-224-5p/SIRT3/AMPK/mTOR axis is involved in the melatonin-mediated inhibition of glucocorticoid-induced osteoporosis by activating autophagy - Sheng Chen; Min Dai (Human Cell, 2023)

Chimeric antigen receptor-natural killer cells: a promising sword against insidious tumor cells - Tahereh Hojjatipour; Zahra Sharifzadeh; Amirhosein Maali; Mehdi Azad (Human Cell, 2023)

Hungatella hathewayi impairs the sensitivity of colorectal cancer cells to 5-FU through decreasing CDX2 expression - Zhi Huang; Chuanlin Wang; Qiujin Huang; Zhiqiang Yan; Zhaohui Yin (Human Cell, 2023)

Vasculature cells control neuroglial co-localization and synaptic connection in a central nervous system tissue mimic system - SongHo Moon; Yuzuru Ito (Human Cell, 2023)

Interplay between LPL and GPIHBP1 in COVID-19 patients: a possible mechanism for post-recovery cardiomyopathy - Mohnad Abdalla; Amr Ahmed El-Arabey; Zhongtao Gai (Human Cell, 2023)

Musashi-1 regulates cell cycle and confers resistance to cisplatin treatment in Group 3/4 medulloblastomas cells - Pablo Shimaoka Chagas; Luciana Chain Veronez; Graziella Ribeiro de Sousa; Gustavo Alencastro Veiga Cruzeiro; Carolina Alves Pereira Corrêa; Fabiano Pinto Saggioro; Rosane Gomes de Paula Queiroz; Suely Kazue Nagahashi Marie; Silvia Regina Brandalise; Izilda Aparecida Cardinalli; José Andres Yunes; Carlos Gilberto Carlotti Júnior; et al. (Human Cell, 2023)

Establishment and characterization of a novel dedifferentiated chondrosarcoma cell line, SMU-DDCS, harboring an IDH1 mutation - Makoto Emori; Naoya Nakahashi; Akira Takasawa; Kenji Murata; Yasutaka Murahashi; Junya Shimizu; Tomohide Tsukahara; Shintaro Sugita; Kohichi Takada; Tadashi Hasegawa; Makoto Osanai; Kosuke Iba (Human Cell, 2023)

KS-EMPD-1: a novel cell line of primary extramammary Paget’s disease - Takamichi Ito; Yuka Tanaka; Toshio Ichiki; Yumiko Kaku-Ito; Takeshi Nakahara (Human Cell, 2023)

Donor-derived CAR-T therapy improves the survival of relapsed B-ALL after allogeneic transplantation compared with donor lymphocyte infusion - Zhao Liang; Hong Xu; Xuan Zhou; JiLong Yang; Sanfang Tu; Yanjie He; Lijuan Zhou; Yuhua Li (Human Cell, 2023)

ROCK2-RNA interaction map reveals multiple biological mechanisms underlying tumor progression in renal cell carcinoma - Zhengdong Hong; Xuexin Chen; Lei Wang; Xiaocheng Zhou; Haowei He; Gaode Zou; Qingnan Liu; Yiqian Wang (Human Cell, 2023)

Efficacy of redox nanoparticles for improving survival of transplanted cells in a mouse model of ischemic stroke - Koji Hirata; Aiki Marushima; Yukio Nagasaki; Hiroshi Ishikawa; Hideaki Matsumura; Arnela Mujagić; Aki Hirayama; Junko Toyomura; Akihiro Ohyama; Shohei Takaoka; Hiroki Bukawa; Akira Matsumura; et al. (Human Cell, 2023)

Exploring the future potential of mesenchymal stem/stromal cells and their derivatives to support assisted reproductive technology for female infertility applications - Andrew Rizano; Ria Margiana; Supardi Supardi; Pety Narulita (Human Cell, 2023)

MiR-3677-3p promotes development and sorafenib resistance of hepatitis B-related hepatocellular carcinoma by inhibiting FOXM1 ubiquitination - Hengzheng He; Jian Zhou; Fahui Cheng; Huijuan Li; Yangya Quan (Human Cell, 2023)

Functions, mechanisms, and clinical applications of lncRNA LINC00857 in cancer pathogenesis - Hussein Aldayyeni; Ahmed Hjazi; Sana Shahab; Jitendra Gupta; Hashem O. Alsaab; Yaseen Hasan Motea; Adeeb Abdulally Abdulhussien alazbjee; Rosario Mireya Romero-Parra; Rasha Fadhel Obaid; Beneen M. Hussien; Seyed Reza Hosseini-Fard (Human Cell, 2023)

Circular RNA circ_KIAA1429 accelerates hepatocellular carcinoma progression via the miR-133a-3p/high mobility group AT-hook 2 (HMGA2) axis in an m6A-dependent manner - Chun-Peng Zhang; Xin-Ying Huang (Human Cell, 2023)

Advances in combined application of dental stem cells and small-molecule drugs in regenerative medicine - Zejun Zheng; Shuai Tang; Tong Yang; Xiaolan Wang; Gang Ding (Human Cell, 2023)

Annexin A9 promotes cell proliferation by regulating the Wnt signaling pathway in colorectal cancer - Xuemei Lu; Liqiang Hu; Jiayan Mao; Shufen Zhang; Ying Cai; Wei Chen (Human Cell, 2023)
Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. Expression of Annexin A9 (ANXA9), a member of the annexin A family, is upregulated in CRC. However, the molecular role of ANXA9 in CRC remains unknown. In the present study, we aimed to investigate the function of ANXA9 and to elucidate the mechanisms underlying its regulation in CRC. In this study, mRNA expression data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and GEPIA database, respectively. Kaplan–Meier analysis was used to analyze the survival rates. LinkedOmics and Metascape databases were used to explore the potential mechanisms of regulation of ANXA9 and to identify genes co-expressed with ANXA9. Finally, in vitro experiments were used to evaluate the function of ANXA9 and explore potential mechanisms. We found that ANXA9 expression was significantly elevated in CRC tissue and cells. High ANXA9 expression was associated with shorter overall survival, poorer disease specific survival, as well as with patient age, clinical stage, M stage, and OS events in CRC. Knockdown of ANXA9 inhibited cell proliferation, invasion, migratory potential, and cell cycle arrest. Mechanistically, functional analysis revealed that genes co-expressed with ANXA9 were mainly enriched in the Wnt signaling pathway. ANXA9 deletion suppressed cell proliferation via the Wnt signaling pathway, while Wnt activation reversed the effects of ANXA9. In conclusion, ANXA9 may promote CRC progression by regulating the Wnt signaling pathway and may be a potential diagnostic biomarker in the clinical management of CRC.

The other side of the coin: mesenchymal stromal cell immortalization beyond evasion of senescence - Luana Suéling Lenz; Márcia Rosângela Wink (Human Cell, 2023)

Impact of CAR-T cell therapy on treating viral infections: unlocking the door to recovery - Nobendu Mukerjee; Swastika Maitra; Arabinda Ghosh; Rohit Sharma (Human Cell, 2023)

PSMD4 drives progression of hepatocellular carcinoma via Akt/COX2 pathway and p53 inhibition - Jiamin Zhang; Shu Fang; Fanghao Rong; Miaomiao Jia; Yunpeng Wang; Huixian Cui; Peipei Hao (Human Cell, 2023)

Embryonic transcription and epigenetics: root of the evil - Leonidas Benetatos; George Vartholomatos (Human Cell, 2023)

Implications of xenobiotic-response element(s) and aryl hydrocarbon receptor in health and diseases - Avijit Mandal; Nabendu Biswas; Md Nur Alam (Human Cell, 2023)

Establishment and characterization of two novel patient-derived cell lines from giant cell tumor of bone - Takuya Ono; Rei Noguchi; Yuki Yoshimatsu; Yooksil Sin; Ryuto Tsuchiya; Taro Akiyama; Naoki Kojima; Yu Toda; Chiaki Sato; Suguru Fukushima; Akihiko Yoshida; Akira Kawai; et al. (Human Cell, 2023)

A pilot study to screen the trisomy 13 from the amniotic fluid puncture - Junbei Xiang; Linfeng Xie; Mianxue Liu; Qian Wan (Human Cell, 2023)

Effects of condensates from volcanic fumaroles and cigarette smoke extracts on airway epithelial cells - Caterina Di Sano; Serena Di Vincenzo; Doriana Lo Piparo; Claudia D’Anna; Simona Taverna; Valentina Lazzara; Paola Pinto; Francesco Sortino; Elisabetta Pace (Human Cell, 2023)
The impact of volcanic airborne products on airway epithelium homeostasis is largely unknown. This study assessed the effects of volcanic Fumarole Condensates (FC) alone or combined with Cigarette Smoke Extracts (CSE) on airway epithelial cells (16HBE and A549). Chemical composition of FC was analyzed by gas chromatography and HPLC. Cells were exposed to FC and IL-33 and IL-8 were assessed. The effects of FC and CSE on cell injury were evaluated assessing cell metabolism/cell viability, mitochondrial stress, cell apoptosis/cell necrosis, and cell proliferation. FC contained: water vapor (70–97%), CO 2 (3–30%), acid gases (H 2 S, SO 2 , HCl, HF) around 1%. FC increased the intracellular IL-33 but differently modulated IL-33 and IL-8 gene expression and IL-8 release in the tested cell lines. FC without/with CSE: (a) increased cell metabolism/cell viability in 16HBE, while decreased it in A549; (b) increased mitochondrial stress in both cell types. FC with CSE increased cell necrosis in A549 in comparison to CSE alone. CSE reduced cell proliferation in 16HB,E while increased it in A549 and FC counteracted these effects in both cell types. Overall, FC induce a pro-inflammatory profile associated to a metabolic reprogramming without a relevant toxicity also in presence of CSE in airway epithelial cells.

BRD4770 inhibits vascular smooth muscle cell proliferation via SUV39H2, but not EHMT2 to protect against neointima formation - Tai-Qiang Chen; Xian Guo; Bo Huo; Xiao-Xuan Zhong; Qun-Hui Wang; Yue Chen; Xue-Hai Zhu; Gao-Ke Feng; Ding-Sheng Jiang; Ze-Min Fang; Xiang Wei (Human Cell, 2023)
The behavior of vascular smooth muscle cells (VSMCs) contributes to the formation of neointima. We previously found that EHMT2 suppressed autophagy activation in VSMCs. BRD4770, an inhibitor of EHMT2/G9a, plays a critical role in several kinds of cancers. However, whether and how BRD4770 regulates the behavior of VSMCs remain unknown. In this study, we evaluate the cellular effect of BRD4770 on VSMCs by series of experiments in vivo and ex vivo. We demonstrated that BRD4770 inhibited VSMCs’ growth by blockage in G2/M phase in VSMCs. Moreover, our results demonstrated that the inhibition of proliferation was independent on autophagy or EHMT2 suppression which we previous reported. Mechanistically, BRD4770 exhibited an off-target effect from EHMT2 and our further study reveal that the proliferation inhibitory effect by BRD4770 was associated with suppressing on SUV39H2/KTM1B. In vivo, BRD4770 was also verified to rescue VIH. Thus, BRD4770 function as a crucial negative regulator of VSMC proliferation via SUV39H2 and G2/M cell cycle arrest and BRD4770 could be a molecule for the therapy of vascular restenosis.

Eight influenza virus cellular manipulations which can boost concurrent SARS-CoV-2 infections to severe outcomes - Kevin Roe (Human Cell, 2023)

Autophagy and apoptosis: regulatory factors of chondrocyte phenotype transition in osteoarthritis - Zhibo Liu; Ting Wang; Xianding Sun; Mao Nie (Human Cell, 2023)

Stem cell sources from human biological waste material: a role for the umbilical cord and dental pulp stem cells for regenerative medicine - Monalisa Das; Alastair J. Sloan (Human Cell, 2023)

Effect of psoralen on the regulation of osteogenic differentiation induced by periodontal stem cell-derived exosomes - Jie Yu; Xiaonan Wu; Wenyi Zhang; Fuhang Chu; Qi Zhang; Meihua Gao; Yingjie Xu; Yingtao Wu (Human Cell, 2023)
Periodontitis is a chronic inflammatory disease that is the main cause of tooth loss in adults, and the key to periodontitis treatment is the repair and regenerate of periodontal bone tissue. Psoralen is the main component of the Psoralea corylifolia Linn, which shows antibacterial, anti-inflammatoryand osteogenic activities. It promotes the differentiation of periodontal ligament stem cells toward osteogenesis. Exosomes secreted by stem cells play important roles in information transmission during the osteogenic differentiation process. The aim of this paper was to investigate the role of psoralen in regulating osteogenic miRNA information in periodontal stem cells and in periodontal stem cells exosomes and the specific mechanism of its action. Experimental results show that exosomes of human periodontal ligament stem cell origin treated with psoralen (hPDLSCs + Pso-Exos) were not significantly different from untreated exosomes (hPDLSC-Exos) in terms of size and morphology. Thirty-five differentially expressed miRNAs were found to be upregulated and 58 differentially expressed miRNAs were found to be downregulated in the hPDLSCs + Pso-Exos compared to the hPDLSC-Exos ( P < 0.05). hsa-miR-125b-5p was associated with osteogenic differentiation. Among them, hsa-miR-125b-5p was associated with osteogenic differentiation. After hsa-miR-125b-5p was inhibited, the osteogenesis level of hPDLSCs was enhanced. In summary, the osteogenic differentiation of hPDLSCs was promoted by psoralen through the downregulation of hsa-miR-125b-5p gene expression in hPDLSCs, and the expression of the hsa-miR-125b-5p gene was also downregulated in exosomes. This finding provides a new therapeutic idea for using psoralen to promote periodontal tissue regeneration.

Novel insights into tumorigenesis and prognosis of endometrial cancer through systematic investigation and validation on mitophagy-related signature - Rui Sun; Xiaoyu Zhou; Tong Wang; Yao Liu; Lina Wei; Ziyi Qiu; Chunping Qiu; Jie Jiang (Human Cell, 2023)

Downregulation of the long noncoding RNA DSCR9 (Down syndrome critical region 9) delays breast cancer progression by modulating microRNA-504-5p-dependent G protein-coupled receptor 65 - Mingzhu Li; Conglin Lin; Zhibing Cai (Human Cell, 2023)

From in vivo to in vitro: exploring the key molecular and cellular aspects of human female gametogenesis - Sarah Abreu Coxir; Guilherme Mattos Jardim Costa; Camilla Fernandes dos Santos; Raquel de Lima Leite Soares Alvarenga; Samyra Maria dos Santos Nassif Lacerda (Human Cell, 2023)

Upregulation of helicase-like transcription factor predicts poor prognosis and facilitates hepatocellular carcinoma progression - Xuesong Cen; Yuyan Lu; Jing Lu; Ping Zhan; Yizhe Cheng; Changhong Luo; Jie Liu; Chengrong Xie; Fuqiang Wang (Human Cell, 2023)

HDAC inhibitor chidamide overcomes drug resistance in chronic myeloid leukemia with the T315i mutation through the Akt–autophagy pathway - Le Yin; Qingyang Zhang; Sisi Xie; Zhao Cheng; Ruijuan Li; Hongkai Zhu; Qian Yu; Huan Yuan; Canfei Wang; Hongling Peng; Guangsen Zhang (Human Cell, 2023)

Roles of non-coding RNAs in the metabolism and pathogenesis of bladder cancer - Daniel Ruben Akiola Sanya; Djamila Onésime (Human Cell, 2023)

ZNRF2 as an oncogene is transcriptionally regulated by CREB1 in breast cancer models - Jin-Tao Liu; Zhen-Xuan Sun; Rui Zhong; Yi-Dan Zhang; Teng Wang; Yu-Dong Hou; Jian-Heng Bao; Lei Zhang; Bo Chen (Human Cell, 2023)

EphA1 aggravates neuropathic pain by activating CXCR4/RhoA/ROCK2 pathway in mice - Qi Li; Rui Li; Xiaoxi Zhu; Xiaolei Chu; Xiaoqiong An; Ming Chen; Lei Zhang; Mingwei Gao; Long Chen (Human Cell, 2023)

Multi-omics data integration reveals the molecular network of dysregulation IQGAP2-mTOR promotes cell proliferation - Tao Chen; Xijie Fan; Guibin Li; Yuhuan Meng (Human Cell, 2023)

Role of cuproptosis in understanding diseases - Shihan Cao; Qian Wang; Zhenzhen Sun; Yue Zhang; Qianqi Liu; Qun Huang; Guixia Ding; Zhanjun Jia (Human Cell, 2023)

Correction: PTEN-induced kinase 1 enhances the reparative effects of bone marrow mesenchymal stromal cells on mice with renal ischaemia/reperfusion-induced acute kidney injury - Chenyu Lin; Wen Chen; Yong Han; Yujie Sun; Xiaoqiong Zhao; Yuan Yue; Binyu Li; Wenmei Fan; Tao Zhang; Li Xiao (Human Cell, 2023)

TEAD4 predicts poor prognosis and transcriptionally targets PLAGL2 in serous ovarian cancer - Xin Tong; Yi-Si Liu; Rui Tong; Wei-Wei Tang; Xue-Mei Li; Chun-Yan Wang; Yong-Peng Wang (Human Cell, 2023)

ZNF677 inhibits oral squamous cell carcinoma growth and tumor stemness by regulating FOXO3a - Zebiao Zhang; Ying Zhang; Xiaoyan Hu; Yanru Chen; Liangliang Zhuang; Shuqin Zhang (Human Cell, 2023)

Neutrophil (dys)function due to altered immuno-metabolic axis in type 2 diabetes: implications in combating infections - Pooja Yedehalli Thimmappa; Sampara Vasishta; Kailash Ganesh; Aswathy S Nair; Manjunath B Joshi (Human Cell, 2023)
Metabolic and inflammatory pathways are highly interdependent, and both systems are dysregulated in Type 2 diabetes (T2D). T2D is associated with pre-activated inflammatory signaling networks, aberrant cytokine production and increased acute phase reactants which leads to a pro-inflammatory ‘feed forward loop’. Nutrient ‘excess’ conditions in T2D with hyperglycemia, elevated lipids and branched-chain amino acids significantly alter the functions of immune cells including neutrophils. Neutrophils are metabolically active cells and utilizes energy from glycolysis, stored glycogen and β -oxidation while depending on the pentose phosphate pathway for NADPH for performing effector functions such as chemotaxis, phagocytosis and forming extracellular traps. Metabolic changes in T2D result in constitutive activation and impeded acquisition of effector or regulatory activities of neutrophils and render T2D subjects for recurrent infections. Increased flux through the polyol and hexosamine pathways, elevated production of advanced glycation end products (AGEs), and activation of protein kinase C isoforms lead to (a) an enhancement in superoxide generation; (b) the stimulation of inflammatory pathways and subsequently to (c) abnormal host responses. Neutrophil dysfunction diminishes the effectiveness of wound healing, successful tissue regeneration and immune surveillance against offending pathogens. Hence, Metabolic reprogramming in neutrophils determines frequency, severity and duration of infections in T2D. The present review discusses the influence of the altered immuno-metabolic axis on neutrophil dysfunction along with challenges and therapeutic opportunities for clinical management of T2D-associated infections.

HAI-1 is required for the novel role of FGFBP1 in maintenance of cell morphology and F-actin rearrangement in human keratinocytes - Dajun D. Lu; Nanxi Huang; Sheng-Wen A. Li; Jessica R. Fang; Chih-Hsin Lai; Jehng-Kang Wang; Khee-Siang Chan; Michael D. Johnson; Chen-Yong Lin (Human Cell, 2023)

Histone methyltransferase SETDB1 promotes osteogenic differentiation in osteoporosis by activating OTX2-mediated BMP-Smad and Wnt/β-catenin pathways - Lianying Hu; Zhen Cheng; Lunan Wu; Liangliang Luo; Ping Pan; Shujin Li; Qiyu Jia; Ning Yang; Bin Xu (Human Cell, 2023)

Advances in mesenchymal stem/stromal cell-based therapy and their extracellular vesicles for skin wound healing - Mohamed J. Saadh; Andrés Alexis Ramírez-Coronel; Ravinder Singh Saini; José Luis Arias-Gonzáles; Ali H. Amin; Juan Carlos Orosco Gavilán; Ioan Sârbu (Human Cell, 2023)

Correction: Dysregulated microRNAs participate in the crosstalk between colorectal cancer and atrial fibrillation - Jiatong Ding; Yuke Cao; Chaofan Qi; Zhen Zong (Human Cell, 2023)

FOXN3 inhibits the progression of ovarian cancer through negatively regulating the expression of RPS15A - Hua Yang; Mingyu Li; Yue Qi (Human Cell, 2023)

Global threat from novel SARS-CoV-2 variants, BF.7, XBB.1.5, BQ.1, and BQ.1.1: variants of concern? - Ryan Varghese; Dileep Kumar; Rohit Sharma (Human Cell, 2023)

Downregulation of argininosuccinate synthase 1 (ASS1) is associated with hypoxia in placental development - Sonia Fantone; Leonardo Ermini; Federica Piani; Nicoletta Di Simone; Greta Barbaro; Stefano Raffaele Giannubilo; Rosaria Gesuita; Giovanni Tossetta; Daniela Marzioni (Human Cell, 2023)

Role of ADAM33 short isoform as a tumor suppressor in the pathogenesis of thyroid cancer via oncogenic function disruption of full-length ADAM33 - Jing Lan; Yehui Zhou; Yang Liu; Yu Xia; Yuqiu Wan; Jianbo Cao (Human Cell, 2023)
Thyroid cancer is the most prevalent endocrine malignancy globally; however, its underlying pathogenesis remains unclarified. Reportedly, alternative splicing is involved in processes such as embryonic stem and precursor cell differentiation, cell lineage reprogramming, and epithelial-mesenchymal transitions. ADAM33-n, an alternative splicing isoform of ADAM33, encodes a small protein containing 138 amino acids of the N-terminal of full-length ADAM33, which constructs a chaperone-like domain that was previously reported to bind and block the proteolysis activity of ADAM33. In this study, we reported for the first time that ADAM33-n was downregulated in thyroid cancer. The results of cell counting kit-8 and colony formation assays showed that ectopic ADAM33-n in papillary thyroid cancer cell lines restricted cell proliferation and colony formation. Moreover, we demonstrated that ectopic ADAM33-n reversed the oncogenic function of full-length ADAM33 in cell growth and colony formation in the MDA-T32 and BCPAP cells. These findings indicate the tumor suppressor ability of ADAM33-n. Altogether, our study findings present a potential explanatory model of how the downregulation of the oncogenic gene ADAM33 promotes the pathogenesis of thyroid cancer.

Dysregulated microRNAs participate in the crosstalk between colorectal cancer and atrial fibrillation - Jiatong Ding; Yuke Cao; Chaofan Qi; Zhen Zong (Human Cell, 2023)

TIPE2 sensitizes breast cancer cells to paclitaxel by suppressing drug-induced autophagy and cancer stem cell properties - Wei Hu; Wenxiang Zheng; Jianxin Du; Zhaobing Tian; Yixin Zhao; Peiqing Zhao; Junsheng Li (Human Cell, 2023)

Mitochondrial transfer in PC-3 cells fingerprinted in ferroptosis sensitivity: a brand new approach targeting cancer metabolism - Amirsadegh Nikoo; Mehryar Habibi Roudkenar; Tomoaki Sato; Yoshikazu Kuwahara; Kazuo Tomita; Zahra Pourmohammadi-Bejarpasi; Nima Najafi-Ghalehlou; Amaneh Mohammadi Roushandeh (Human Cell, 2023)

Onionin A inhibits small-cell lung cancer proliferation through suppressing STAT3 activation induced by macrophages-derived IL-6 and cell–cell interaction with tumor-associated macrophage - Remi Mito; Toyohisa Iriki; Yukio Fujiwara; Cheng Pan; Tsuyoshi Ikeda; Toshihiro Nohara; Makoto Suzuki; Takuro Sakagami; Yoshihiro Komohara (Human Cell, 2023)
Tumor-associated macrophage (TAM)-derived IL-6 is involved in small-cell lung cancer (SCLC) progression and chemoresistance via the activation of signal transducer and activator of transcription 3 (STAT3) in the tumor microenvironment. This study aimed to identify natural compounds that suppress cell–cell interactions between TAMs and SCLC cells by inhibiting STAT3 activation. We used a library of natural compounds to identify candidate agents possessing anti-SCLC effects by inhibiting macrophage-induced tumor proliferation. SBC-3 and SBC-5, human SCLC cell lines, were used for in vitro experiments. Furthermore, we assessed the efficacy of these candidate agents in a murine xenograft model of human SCLC. Among the natural compounds examined, onionin A (ONA) inhibited IL-6-induced STAT3 activation and SCLC cell proliferation. ONA also reduced the secretion of IL-6 from macrophages and interfered with the direct effect of cell–cell interactions between macrophages and SCLC cells. Furthermore, ONA administration suppressed tumor progression in a tumor-bearing mouse model. ONA was identified as the most useful candidate for targeting cell–cell interactions between cancer cells and TAMs for anti-SCLC therapy.

Bone marrow mesenchymal stem cells derived exosomal Lnc TUG1 promotes bone fracture recovery via miR-22-5p/Anxa8 axis - Wei Li; Lihong Li; Rui Cui; Xiaoqing Chen; Haifeng Hu; Yuyu Qiu (Human Cell, 2023)
Bone fracture healing is a complex physiologic process that involves changes in the expression of several thousand genes. Long noncoding RNAs (lncRNAs) may have critical biological roles in this process. The objectives of the present study were to determine whether BMSC-derived exosomal lncTUG1 can enhance osteogenic differentiation and thereby promoting bone fracture recovery and to investigate its potential mechanisms of action. Bone marrow mesenchymal stromal cells were isolated from mice and cultured for the following experiments. After adipogenic and osteogenic differentiation induction, Oil Red O, alizarin red S, and alkaline phosphatase staining solutions were applied to confirm the formation of lipid droplets and calcium nodules. Western blotting analyses, real-time reverse transcription PCR assays, luciferase reporter were performed to confirm relative RNA and protein expressions and luciferase activities of transfected cells. RNA pull-down and RNA immunoprecipitation assays were also carried to verify the interaction between lncTUG1 and miR-22-5p. Additionally, a mouse model of closed femoral fractures was generated to evaluate the in vivo effect of increased lncTUG1 on fracture healing. BMSC-derived exosomal lncTUG1 enhanced the activity of osteoblasts. Overexpression of miR-22-5p reversed the osteopromoting effect of increased lncTUG1. The knockdown of Anxa8 reversed the osteogenic effect of miR-22-5p inhibitors, indicating an interaction between Anxa8 and miR-22-5p. Upregulation of lncTUG1 could promote the fracture recovery in vivo. In conclusion, the present study highlights the functional importance of BMSC-derived exosomal lncTUG1 in the process of bone fracture recovery.

Exosomes derived from mesenchymal stromal cells: a promising treatment for pelvic floor dysfunction - Leimei Xu; Yizhen Sima; Chengzhen Xiao; Yisong Chen (Human Cell, 2023)

Reduced expression of gangliosides with GM2-determinant in cervical carcinoma-derived cells after subcutaneous transplantation into nude mice - Kyoko Tanaka; Isao Murakami; Mikio Mikami; Daisuke Aoki; Masao Iwamori (Human Cell, 2023)
Human cervical carcinoma-derived cell lines have been frequently found to contain gangliosides with GM2-determinant, i.e., GM2, GalNAc-GM1b and GalNAc-GD1a, but GM2 was only detected in 5 of 15 tissues, and GalNAc-GM1b and GalNAc-GD1a were not found in any tissues from patients with several histological types of cervical carcinomas. To further characterize the ganglioside expression in cervical carcinomas, cells were grown by subcutaneous transplantation into nude mice, and gangliosides were quantitated by TLC-immunostaining with the anti-GM2 (YHD-06) antibody and a newly developed anti-GM3 (5H6) antibody, which reacts with GM3 and GM1b, but not with GD1a. Gangliosides with GM2-determinant in cells disappeared in transplanted cells, and the amount of GM3, a precursor for GM2, in transplanted cells was greater than in cultured cells. Also, transplanted cells containing GalNAc-GM1b newly expressed GM1b, suggesting that the activity of GalNAc transferase for synthesis of GalNAc-GM1b is retarded on subcutaneous transplantation. The ganglioside composition, with GM3 as the major one, in the transplanted cells was similar to that in cervical carcinoma tissues, and thus, the expression of gangliosides with GM2-determinant seemed to be accelerated under cell-cultivation conditions.

Ferroptosis in pancreatic diseases: potential opportunities and challenges that require attention - Zhao Zhirong; Han Li; Liu Yi; Zhou Lichen; Dai Ruiwu (Human Cell, 2023)

Identification of LBH and SPP1 involved in hepatic stellate cell activation during liver fibrogenesis - Weiming Dai; Yuecheng Guo; Zhenyang Shen; Junjun Wang; Lungen Lu; Hui Dong; Xiaobo Cai (Human Cell, 2023)

Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) as an undetermined tool in tumor cells - Parviz Azimnasab-sorkhabi; Maryam Soltani-asl; Jose´ Roberto Kfoury Junior (Human Cell, 2023)

Paraoxonase-2 is upregulated in triple negative breast cancer and contributes to tumor progression and chemoresistance - Roberto Campagna; Valentina Pozzi; Sara Giorgini; Doriana Morichetti; Gaia Goteri; Davide Sartini; Emma Nicol Serritelli; Monica Emanuelli (Human Cell, 2023)

Prognostic and functional roles of EIF4G1 in lung squamous cell carcinoma - Baoxin Bai; Lin Dong; Minghao Feng; Zhiwen Zhang; Ying Lu; Zengguang Xu; Yali Liu (Human Cell, 2023)
Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) is highly expressed in many cancers and affects their occurrence and development. However, the effect of EIF4G1 on the prognosis, biological function and the relevant mechanism in lung squamous cell carcinoma (LSCC) is unclear. Through clinical cases, Cox’s proportional hazard model and Kaplan–Meier plotter survival analysis, we find the expression levels of EIF4G1 are dependent on age and clinical stage, high expression of EIF4G1 could be used to predict the overall survival of LSCC patients. LSCC cell line NCI-H1703, NCI-H226 and SK-MES-1infected with EIF4G1 siRNA are used to detect the function of EIF4G1 with cell proliferation and tumorigenesis in vivo and vitro. The data show that EIF4G1 promotes tumor cell proliferation and the G1/S transition of cell cycle in LSCC, then the biological function of LSCC is effected by the AKT/mTOR pathway. Above all, these results have demonstrated that EIF4G1 promotes LSCC cell proliferation and may represent an indicator of prognosis in LSCC.

A prognostic risk model, tumor immune environment modulation, and drug prediction of ferroptosis and amino acid metabolism-related genes in hepatocellular carcinoma - Lina Ji; Qianqian Zhang; Yumeng Cao; Lixin Liu (Human Cell, 2023)

Promotion of ferroptosis in head and neck cancer with divalent metal transporter 1 inhibition or salinomycin - Jaewang Lee; Jong-Lyel Roh (Human Cell, 2023)

Long non-coding RNAs in osteoporosis: from mechanisms of action to therapeutic potential - Jianglin Hou; Da Liu; Jihui Zhao; Sen Qin; Senxiang Chen; Zimo Zhou (Human Cell, 2023)

Clinical significance and biofunction of ZNF384 in renal cell carcinoma discovered by data mining and experimentation - Fangshi Xu; XiaoJie Yang; Li Xue; Peng Zhang; Tie Chong; Yi Sun (Human Cell, 2023)

Insights into the characteristics of primary radioresistant cervical cancer using single-cell transcriptomics - Biyuan Xing; Congli Pu; Yunshang Chen; Yuhan Sheng; Baofang Zhang; Jie Cui; Gang Wu; Yingchao Zhao (Human Cell, 2023)
Radioresistance is a major cause of radiotherapy failure among patients with cervical cancer (CC), the fourth most common cause of cancer mortality in women worldwide. Traditional CC cell lines lose intra-tumoral heterogeneity, posing a challenge for radioresistance research. Meanwhile, conditional reprogramming (CR) maintains intra-tumoral heterogeneity and complexity, as well as the genomic and clinical characteristics of original cells and tissues. Three radioresistant and two radiosensitive primary CC cell lines were developed under CR conditions from patient specimens, and their characteristics were verified via immunofluorescence, growth kinetics, clone forming assay, xenografting, and immunohistochemistry. The CR cell lines had homogenous characteristics with original tumor tissues and maintained radiosensitivity in vitro and in vivo, while also maintaining intra-tumoral heterogeneity according to single-cell RNA sequencing analysis. Upon further investigation, 20.83% of cells in radioresistant CR cell lines aggregated in the G2/M cell cycle phase, which is sensitive to radiation, compared to 38.1% of cells in radiosensitive CR cell lines. This study established three radioresistant and two radiosensitive CC cell lines through CR, which will benefit further research investigating radiosensitivity in CC. Our present study may provide an ideal model for research on development of radioresistance and potential therapeutic targets in CC.

Microenvironmental elements singularity synergistically regulate the behavior and chemosensitivity of endometrioid carcinoma - Sayuri Morito; Maki Kawasaki; Megumi Nishiyama; Takehisa Sakumoto; Mariko Hashiguchi; Takayuki Narita; Atsushi Kawaguchi; Shuji Toda; Shigehisa Aoki (Human Cell, 2023)

Beauty and the beast: host microRNA-155 versus SARS-CoV-2 - K. I. Papadopoulos; A. Papadopoulou; T. C. Aw (Human Cell, 2023)

Human umbilical cord mesenchymal stem cell-derived TGFBI attenuates streptozotocin-induced type 1 diabetes mellitus by inhibiting T-cell proliferation - Chushan Wu; Weijiang Liu; Yuanlin Liu; Tingting Xu; Man Li; Xue Li; Yang Wang; Guangyu Meng; Lu Li; Rongxiu Zheng; Yi Zhang (Human Cell, 2023)
MSCs have been demonstrated to have a great benefit for type 1 diabetes mellitus (T1DM) due to their strong immunosuppressive and regenerative capacity. However, the comprehensive mechanism is still unclear. Our previous study indicated that transforming growth factor beta induced (TGFBI) is highly expressed in human umbilical cord-derived mesenchymal stem or stromal cells (hUC-MSCs), which are also implicated in T1DM. In this study, we found that infusion of TGFBI knockdown hUC-MSCs displayed impaired therapeutic effects in T1DM mice and decreased immunosuppressive capability. TGFBI knockdown hUC-MSCs could increase the proportion of T-cell infiltration while increasing the expression of IFN-gamma and interleukin-17A in the spleen. In addition, we also revealed that hUC-MSC-derived TGFBI could repress activated T-cell proliferation by interfering with G1/S checkpoint CyclinD2 expression. Our results demonstrate that TGFBI plays a critical role in MSC immunologic regulation. TGFBI could be a new immunoregulatory molecule controlling MSC function for new treatments of T1DM. Graphical Abstract Schematic Representation of the Immunosuppression capacity of hUC-MSC by TGFBI

The role of non-coding RNA in lupus nephritis - Hanzhi Liang; Qinghua Liu (Human Cell, 2023)

CircRNA_0017076 acts as a sponge for miR-185-5p in the control of epithelial-to-mesenchymal transition of tubular epithelial cells during renal interstitial fibrosis - Fan Zhang; Huimei Zou; Xiaoying Li; Jun Liu; Ying Xie; Min Chen; Jie Yu; Xin Wu; Bing Guo (Human Cell, 2023)

Impact of umbilical cord mesenchymal stromal/stem cell secretome and cord blood serum in prostate cancer progression - André Sousa; Pedro Coelho; Fernanda Leite; Catarina Teixeira; Ana Catarina Rocha; Inês Santos; Pilar Baylina; Ruben Fernandes; Raquel Soares; Raquel Costa; Andreia Gomes (Human Cell, 2023)
Prostate cancer (PCa) is the second most common malignancy in men, and the fifth leading cause of death worldwide. Mesenchymal stromal/stem cells (MSC) have been identified in PCa, although contradictory effects in malignant transformation and tumor progression have been described. Since umbilical cord (UC) MSC and cord blood serum (CBS) are rich in numerous growth and anti-inflammatory factors, UC-MSC secretome and CBS are able to modulate tumor cell proliferation and survival as well as immunity and angiogenesis. In the present study, we address this relationship and investigate the influence of UC-MSC secretome and CBS on two human PCa cell lines (PC3 and LNCaP) and a normal epithelial prostate cell line (HPEpiC). Our results disclosed that upon exposure to UC-MSC-conditioned medium or CBS, both PC3 and LNCaP cells exhibited reduced viability, proliferation, and motility while non-malignant epithelial prostate cells were unaffected. These findings were corroborated by expression analysis of AKT/PI3K signaling pathway, p53 and interleukin genes. UC-MSC and CBS factors decreased the expression of growth-stimulating AKT and PI3K effectors and simultaneously up-regulated the expression of tumor-suppressor p53. Moreover, a more anti-inflammatory expression profile was found in both malignant PCa cell lines. Altogether, these results shed light into possible mechanisms by which UC-MSC and CBS reduce PCa progression, further reinforcing their potential use as novel therapeutic agents in PCa. Graphical abstract

Correction to: Systematic single-cell dissecting reveals heterogeneous oncofetal reprogramming in the tumor microenvironment of gastric cancer - Shaocong Mo; Xin Shen; Yulin Wang; YunPeng Liu; Takehito Sugasawa; ZongCheng Yang; Wenchao Gu; Takahito Nakajima (Human Cell, 2023)

Correction to: Cl-amidine attenuates lipopolysaccharide-induced inflammation in human gingival fibroblasts via the JNK/MAPK, NF-κB, and Nrf2 signalling pathways - Jianxin Du; Ning Wang; Hui Sun; Linlin Zheng; Xiangqin Qi (Human Cell, 2023)

Paraoxonase-2 expression in oral squamous cell carcinoma - Roberto Campagna; Valentina Pozzi; Alessia Salvucci; Lucrezia Togni; Marco Mascitti; Davide Sartini; Eleonora Salvolini; Andrea Santarelli; Lorenzo Lo Muzio; Monica Emanuelli (Human Cell, 2023)

Novel insights into the angiogenic function of JMJD2B in diabetic hind limb ischemia: involvement of activating Wnt/β-catenin pathway - Zhiwei Wang; Mingxing Li; Yuanfeng Liu; Zhentao Qiao; Xufeng Zu; Tao Cao; Tao Bai (Human Cell, 2023)

Three dimensional models of dedifferentiated liposarcoma cell lines: scaffold-based and scaffold-free approaches - Sayumi Tahara; Fernanda Costas C. de Faria; Patricia Sarchet; Federica Calore; Joe Sharick; Jennifer L. Leight; Lucia Casadei; Raphael E. Pollock (Human Cell, 2023)

Recent updates of stem cell-based erythropoiesis - Heeju Han; Yeri Alice Rim; Ji Hyeon Ju (Human Cell, 2023)

MiR-326 regulates cell proliferation and apoptosis in fibroblast-like synoviocytes in rheumatoid arthritis - Wang Yiou; Wang Zhihong; Zhu Shibai; Li Shanni; Qian Wenwei (Human Cell, 2023)

Emergence of monkeypox: a worldwide public health crisis - J. P. Shabaaz Begum; Leirika Ngangom; Prabhakar Semwal; Sakshi Painuli; Rohit Sharma; Ashim Gupta (Human Cell, 2023)

The reversibility of cancer radioresistance: a novel potential way to identify factors contributing to tumor radioresistance - Yoshikazu Kuwahara; Kazuo Tomita; Mehryar Habibi Roudkenar; Amaneh Mohammadi Roushandeh; Tomoaki Sato; Akihiro Kurimasa (Human Cell, 2023)

Silencing of adipocyte enhancer-binding protein 1 (AEBP1) alleviates renal fibrosis in vivo and in vitro via inhibition of the β-catenin signaling pathway - Naiquan Liu; Dajun Liu; Shiyu Cao; Jing Lei (Human Cell, 2023)

Inhalant cannabidiol impedes tumor growth through decreased tumor stemness and impaired angiogenic switch in NCI-H1437-induced human lung cancer model - Évila Lopes Salles; Sahar Emami Naeini; Hesam Khodadadi; Bidhan Bhandari; Sholeh Rezaee; Edie Threlkeld; Hannah M. Rogers; Vincenzo Costigliola; Alvin V. Terry; David C. Hess; Sumitra Deb; Swati Palit Deb; et al. (Human Cell, 2023)

Oral-specific microenvironments regulate cell behavior and anticancer drug sensitivity of tongue squamous cell carcinoma - Shuhei Iwamoto; Megumi Nishiyama; Maki Kawasaki; Sayuri Morito; Takehisa Sakumoto; Shuji Toda; Yoshio Yamashita; Shigehisa Aoki (Human Cell, 2023)

ARHGAP6 inhibits bladder cancer cell viability, migration, and invasion via β-catenin signaling and enhances mitomycin C sensitivity - Weihua Chen; Mingyue Tan; Chao Yu; Guoqiang Liao; Dehui Kong; Jie Bai; Bo Yang; Hua Gong (Human Cell, 2023)

A prognostic cuproptosis-related lncRNA predictive signature for bladder cancer patients - Shaoqin Jiang; Jili Zhang; Qi Fan; Zhihao Li; Ruiling Dou; Zequn Lin; Zhenlin Chen; Yue Xu; Zhangcheng Huang; Jingyuan Lan; Wenwen Lin; Sijie Xu; et al. (Human Cell, 2023)

Possible role of combined therapy targeting MET and pro-HGF activation for renal cell carcinoma: analysis by human HGF-producing SCID mice - Masato Fujii; Takahiro Akioka; Shoichi Kimura; Takahiro Nagai; Takumi Kiwaki; Tsuyoshi Fukushima; Shoichiro Mukai; Toshiyuki Kamoto (Human Cell, 2023)

Hyperinflammatory disease and vasculitis-associated autoimmune disease pathogenesis by novel virulent pathogens inducing lymphocyte exhaustion and/or suppression - Kevin Roe (Human Cell, 2023)

Regulatory role of apelin receptor signaling in migration and differentiation of mouse embryonic stem cell-derived mesoderm cells and mesenchymal stem/stromal cells - Hatice Burcu Şişli; Selinay Şenkal; Taha Bartu Hayal; Ezgi Bulut; Ayşegül Doğan (Human Cell, 2023)

Systematic single-cell dissecting reveals heterogeneous oncofetal reprogramming in the tumor microenvironment of gastric cancer - Shaocong Mo; Xin Shen; Yulin Wang; YunPeng Liu; Takehito Sugasawa; ZongCheng Yang; Wenchao Gu; Takahito Nakajima (Human Cell, 2023)

Establishment and characterization of a new intrahepatic cholangiocarcinoma cell line, ICC-X3 - Hao Xu; Wei Luo; Zhenjie Zhao; Xin Miao; Changpeng Chai; Jinjing Hu; Huan Tang; Hui Zhang; Wence Zhou (Human Cell, 2023)

Establishment and characterization of NCC-DSM1-C1: a novel cell line derived from a patient with desmoid fibromatosis - Taro Akiyama; Yuki Yoshimatsu; Rei Noguchi; Yooksil Sin; Julia Osaki; Takuya Ono; Yuki Adachi; Ryuto Tsuchiya; Yu Toda; Eisuke Kobayashi; Naoki Kojima; Akihiko Yoshida; et al. (Human Cell, 2023)

SPOCK2 and SPRED1 function downstream of EZH2 to impede the malignant progression of lung adenocarcinoma in vitro and in vivo - Yang Liu; Xiaoxi Fan; Changrui Jiang; Shun Xu (Human Cell, 2023)
Enhancer of zeste homolog 2 (EZH2) is an important epigenetic regulator, and is associated with the malignant progression of lung cancer. However, the mechanisms of EZH2 on lung adenocarcinoma (LUAD) remain unclear. The relationship between EZH2 and SPOCK2 or SPRED1 was confirmed by dual-luciferase reporter assay. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed to examine the expression of SPOCK2 and SPRED1 and their prognostic values of LUAD. The effects of SPOCK2 and SPRED1 on the biological characters of LUAD cells were identified on functional assays in vitro and in vivo. Our results showed that EZH2 suppressed the expression and transcriptional activity of SPOCK2 and SPRED1, and these effects were reversed by the EZH2 inhibitor, Tazemetostat. SPOCK2 and SPRED1 were expressed at low levels in LUAD patients, and a high expression level of SPOCK2 or SPRED1 predicted better survival. Moreover, overexpression of SPOCK2 or SPRED1 could inhibit tumoral proliferation, migration ratio, and invasion activity in vitro as well as retard tumor growth in vivo. However, EZH2 elevation could rescue these impacts and accelerate LUAD progression. Our findings reveal that SPOCK2 and SPRED1 are epigenetically suppressed by EZH2 and may act as novel regulators to inhibit the proliferation, migration, and invasion of LUAD cells.

Chronic intermittent hypoxia-induced BNIP3 expression mitigates contractile dysfunction and myocardial injury in animal and cell model via modulating autophagy - Ruifang Chi; Chanjuan Chai; Gaizhen Liu; Huili Cao; Bin Yang (Human Cell, 2023)

Circular RNA hsa_circ_0000519 contributes to angiogenesis and tumor progression in hepatocellular carcinoma through the miR-1296/E2F7 axis - Yi Liu; Hui Tang; Yaling Zhang; Qian Wang; Shiying Li; Zhiyi Wang; Xiaofeng Shi (Human Cell, 2023)

CircMAN1A2 contributes to nasopharyngeal carcinoma progression via enhancing the ubiquitination of ATMIN through miR-135a-3p/UBR5 axis - Qian-Qian Dang; Pei-Hong Li; Juan Wang; Jing-Yi Zhao; Su-Nan Zhai; Ying-Juan Zheng; Dao-Ke Yang (Human Cell, 2023)

METTL3-mediated Hsa_circ_0000390 downregulation enhances the proliferation, migration, and invasion of colorectal cancer cells by increasing Notch1 expression - Junwei Tang; Mei Huang; Hong Peng; Jing He; Lei Gong; Mei Yang; Xi Zhao; Yang Zhao; Heping Zheng (Human Cell, 2023)

Expansion of human amniotic epithelial cells using condition cell reprogramming technology - Aisha Naeem; Muhammad Umer Choudhry; Alex Kroemer; Simone Wahnschafft; Wanxing Cui; Chris Albanese (Human Cell, 2022)
Human amniotic epithelial cells (hAECs) are non-immunogenic epithelial cells that can develop into cells of all three germline lineages. However, a refined clinically reliable method is required to optimize the preparation and banking procedures of hAECs for their successful translation into clinical studies. With the goal of establishing standardized clinically applicable hAECs cultured cells, we described the use of a powerful epithelial cell culture technique, termed C onditionally R eprogrammed Cells (CRC) for ex vivo expansion of hAECs. The well-established CRC culture method uses a Rho kinase inhibitor (Y-27632) and J2 mouse fibroblast feeder cells to drive the indefinite proliferation of all known epithelial cell types. In this study, we used an optimized CRC protocol to successfully culture hAECs in a CRC medium supplemented with xenogen-free human serum. We established that hAECs thrive under the CRC conditions for over 5 passages while still expressing pluripotent stem markers (OCT-4, SOX-2 and NANOG) and non-immunogenic markers (CD80, CD86 and HLA-G) suggesting that even late-passage hAECs retain their privileged phenotype. The hAECs-CRC cells were infected with a puromycin-selectable lentivirus expressing luciferase and GFP (green fluorescent protein) and stably selected with puromycin. The hAECs expressing GFP were injected subcutaneously into the flanks of Athymic and C57BL6 mice to check the tolerability and stability of cells against the immune system. Chemiluminescence imaging confirmed the presence and viability of cells at days 2, 5, and 42 without acute inflammation or any tumor formation. Collectively, these data indicate that the CRC approach offers a novel solution to expanding hAECs in humanized conditions for future clinical uses, while retaining their primary phenotype. Graphical abstract

Piezo protein determines stem cell fate by transmitting mechanical signals - Xiaolei Qiu; Zhuoyue Deng; Meijing Wang; Yuqi Feng; Lintao Bi; Lisha Li (Human Cell, 2022)

Expression of estrogen receptors, PELP1, and SRC in human spermatozoa and their associations with semen quality - Izabela Skibińska; Mirosław Andrusiewicz; Magdalena Jendraszak; Aleksandra Żbikowska; Piotr Jędrzejczak; Małgorzata Kotwicka (Human Cell, 2022)
Sperm cells are target cells for both estrogens and xenoestrogens. Due to the specific structure of spermatozoa, these hormonal compounds may act on sperm in a non-genomic mechanism only. However, the ESR-mediated signaling pathways are still poorly understood. In this study, we obtained 119 samples from male participants of Caucasian descent who donated semen for standard analysis. We analyzed gene expression of estrogen receptors ( ESR1 and ESR2 ) and their coregulators—proline-, glutamic acid-, and leucine-rich protein 1 ( PELP1 ), and cellular kinase c-Src ( SRC ). RNA level was established using reverse-transcribed RNA as a template, followed by a polymerase chain reaction. Proteins’ presence was confirmed by western blot and immunocytochemistry techniques. “Normal” values of semen parameters were defined as follows: > 32% sperm with progressive motility, > 4% sperm cells with normal morphology, > 15 × 10 6 sperm per mL, > 58% live spermatozoa and leukocyte amount < 10 6 cells per mL, according to WHO 2010 reference. Semen parameters that deviated from these “normal” values were labeled as “abnormal”. Gene expression ratios revealed significant, moderate, and negative correlations for ESR1 / ESR2 and weak, negative ESR2 / PELP1 correlations in the subgroup of patients with abnormal values of semen parameters. In addition, SRC/PELP1 was moderately and positively correlated in the subgroup with parameters within the reference values established by WHO 2010. Our study showed that both PELP1 scaffolding protein and SRC kinase might influence semen quality via ESRs. It seems that not the expression of a single gene may affect the sperm quality, but more gene-to-gene mutual ratio. Characterization of estrogen-signaling pathway-related genes’ modulated expression in sperm cells could aid in better understanding sperm biology and quality.

Silencing RPL8 inhibits the progression of hepatocellular carcinoma by down-regulating the mTORC1 signalling pathway - Tao Sun; Weiying Zhu; Qingjing Ru; Yi Zheng (Human Cell, 2022)

The roles of ETS transcription factors in liver fibrosis - Li-Ye Zhang; Yong Tan; Xiao-Jie Luo; Jiang-Feng Wu; Yi-Ran Ni (Human Cell, 2022)

Heterophyllin B inhibits the malignant phenotypes of gastric cancer cells via CXCR4 - Yunhai Wei; Lei Yin; Jinyu Zhang; Jianing Tang; Xiaofeng Yu; Zhongxin Wu; Yuhai Gao (Human Cell, 2022)

Recent topics and advanced therapies in chronic granulomatous disease - Hiroyuki Nunoi; Hideki Nakamura; Toyoki Nishimura; Makoto Matsukura (Human Cell, 2022)

Roles of RNA-binding proteins in neurological disorders, COVID-19, and cancer - Daniel Ruben Akiola Sanya; Claudia Cava; Djamila Onésime (Human Cell, 2022)

Microfibril-associated protein 2 is activated by POU class 2 homeobox 1 and promotes tumor growth and metastasis in tongue squamous cell carcinoma - Bo Yan; Qiang Sun; Hong Zhou; Xuanping Cao (Human Cell, 2022)

Induction of premature senescence and a less-fibrogenic phenotype by programmed cell death 4 knockdown in the human hepatic stellate cell line Lieming Xu-2 - Rasheda Perveen; Iwata Ozaki; M. Manirujjaman; Keiichiro Mine; Yuzo Murata; Kenichi Tanaka; Jinghe Xia; Hirokazu Takahashi; Keizo Anzai; Sachiko Matsuhashi (Human Cell, 2022)
Although programmed cell death 4 (PDCD4) was initially reported as a tumor suppressor and has been shown to inhibit cancer cell growth and metastasis, recent studies have demonstrated that loss of PDCD4 expression also induces growth inhibition by inducing apoptosis and/or cellular senescence. At present, the roles of PDCD4 in the activation and profibrogenic properties of myofibroblasts, which are critically involved in organ fibrosis, such as that in the liver, are unclear. We, therefore, investigated the roles of PDCD4 in myofibroblasts using human hepatic stellate cell line Lieming Xu-2 (LX-2). PDCD4 knockdown inhibited LX-2 proliferation and induced a senescent phenotype with increased β-galactosidase staining and p21 expression in a p53-independent manner together with downregulation of the notch signaling mediator RBJ-κ/CSL. During PDCD4 knockdown, alpha smooth muscle actin (α-SMA; an activation marker of myofibroblasts), matrix metalloproteinases MMP-1 and MMP-9, and collagen IV were upregulated, but the expression of collagen1α1 and collagen III was markedly downregulated without any marked change in the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1). These results demonstrated that knockdown of PDCD4 induced the cellular senescence phenotype and activated myofibroblasts while suppressing the profibrogenic phenotype, suggesting roles of PDCD4 in cellular senescence and fibrogenesis in the liver.

Construction of a m5C-related long non-coding RNA signature for the prognosis of hepatocellular carcinoma - Jing Lu; Haoyu Wang; Wanyue Cao; Desheng Chen; Zeping He; Junming Xu (Human Cell, 2022)

Establishment and comprehensive analysis of a new human cell line (NK-NJ) with NK-cell characteristics established from extranodal natural killer cell lymphoma/leukemia - Jin-Hua Liang; Wei-Ting Wang; Kai-Xin Du; Tong-Yao Xing; Yan Wang; Hui Wang; Lu Liu; Rui Guo; Yang Shao; Junheng Liang; Yue Li; Hao-Rui Shen; et al. (Human Cell, 2022)