Human Cell最新文献

{"title":"The role of RhoA-ROCK signaling in benign prostatic hyperplasia: a review.","authors":"Shidong Shan, Min Su","doi":"10.1007/s13577-025-01179-x","DOIUrl":"https://doi.org/10.1007/s13577-025-01179-x","url":null,"abstract":"<p><p>Benign prostatic hyperplasia (BPH) is a common urological disease in middle-aged and elderly men. The main pathological mechanisms of BPH include static factors that increase prostate volume and dynamic factors that increase prostate tension. The RhoA/ROCK signaling pathway is a classical pathway that regulates cell contraction, migration, and growth. In this review, we summarize the potential role of RhoA/ROCK signaling in the development of BPH. The RhoA/ROCK signaling pathway can enhance the contraction of prostate smooth muscle through the Ca²⁺ sensitization pathway and increase passive tension in the prostate through tissue fibrosis. Additionally, RhoA/ROCK signaling promotes cell proliferation by regulating cell division and may influence apoptosis by affecting the actin cytoskeleton. Furthermore, risk factors, such as inflammation, metabolic syndrome, and hormonal changes, can upregulate RhoA/ROCK signaling, which in turn promotes these risk factors, eventually leading to the development of BPH. Given the role of RhoA/ROCK signaling in regulating multiple pathogenic factors of BPH, this pathway represents a promising molecular target for BPH treatment and warrants further study.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 2","pages":"48"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of a human ovarian endometrioid carcinoma cell line by constitutive expression of cyclin-dependent kinase 4, cyclin D1 and telomerase reverse transcriptase.","authors":"Hitomi Hoshino, Tomoya O Akama, Daisuke Inoue, Suzuko Moritani, Shohei Shigeto, Kazuyuki Matsuda, Hisato Yoshida, Natsumi Yonemoto, Mana Fukushima, Yoshio Yoshida, Motohiro Kobayashi","doi":"10.1007/s13577-025-01176-0","DOIUrl":"10.1007/s13577-025-01176-0","url":null,"abstract":"<p><p>Only a few human ovarian endometrioid carcinoma cell lines are currently available, partly due to the difficulty of establishing cell lines from low-grade cancers. Here, using a cell immortalization strategy consisting of i) inactivation of the p16^INK4a-pRb pathway by constitutive expression of mutant cyclin-dependent kinase 4 (R24C) (CDK4^R24C) and cyclin D1, and ii) acquisition of telomerase reverse transcriptase (TERT) activity, we established a human ovarian endometrioid carcinoma cell line from a 46-year-old Japanese woman. That line, designated JFE-21, has proliferated continuously for over 6 months with a doubling time of ~ 55 h. JFE-21 cells exhibit polygonal shapes and proliferate without contact inhibition to form a monolayer in a jigsaw puzzle-like arrangement. Ultrastructurally, JFE-21 cells exhibit well-developed rough endoplasmic reticulum, mitochondria and lysosomes in the cytoplasm, with cells contacting each other via desmosomes. G-band karyotype analysis indicated that cells had a near-tetraploid karyotype. Immunofluorescence staining revealed that the expression profile of a series of ovarian carcinoma markers in JFE-21 cells was consistent with ovarian endometrioid carcinoma. Moreover, Sanger sequencing of DNA polymerase ε (POLE) gene and immunohistochemical analysis of mismatch repair (MMR) proteins revealed that JFE-21 cells were classified as the no specific molecular profile (NSMP) subtype. In addition, JFE-21 cells were sensitive to paclitaxel and carboplatin administered to the donor as therapy. These findings indicate that constitutive expression of CDK4^R24C, cyclin D1 and TERT genes may be an option to establish cell lines from low-grade cancers, including ovarian endometrioid carcinoma.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 2","pages":"47"},"PeriodicalIF":3.4,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11779770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nimodipine ameliorates subarachnoid hemorrhage-induced neuroinflammation and injury by protecting mitochondrial function and regulating autophagy.","authors":"Liqiu Ma, Lan Yao, Zhaowei Zhang, Bing Hao","doi":"10.1007/s13577-025-01174-2","DOIUrl":"https://doi.org/10.1007/s13577-025-01174-2","url":null,"abstract":"<p><p>Subarachnoid hemorrhage (SAH) is a type of hemorrhagic stroke, and the neuroprotective effects of nimodipine following SAH have been well-documented. Sirtuin 3 (SIRT3), a mitochondrial nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase, plays a significant role in mitigating oxidative stress in various neurodegenerative conditions. However, the role of SIRT3 in the neuroprotective mechanisms of nimodipine after SAH remains unclear. In this study, the in vitro cytotoxicity of neurons exposed to 2% ethanol (to stimulate oxidative stress) was assessed. An in vivo experimental SAH model was established in adult mice through internal carotid perforation. A series of in vitro and in vivo experiments were conducted to investigate the function of SIRT3 and its potential mechanisms in nimodipine-treated SAH. Nimodipine, at a concentration of 10 μM within 48 h of incubation, exerted significant neuroprotective effects, enhancing SIRT3 protein expression under oxidative stress. Functional in vitro studies revealed that elevated SIRT3 expression improved mitochondrial function and promoted neuronal autophagy. Additional studies unveiled that SIRT3 knockdown or inhibition of autophagosome formation using inhibitor 3-methyladenine suppressed nimodipine-induced autophagy. The absence of autophagy increased neuronal cytotoxicity and mitochondrial dysfunction, decreased the release of anti-inflammatory cytokines, and increased the release of proinflammatory cytokines. Furthermore, blocking autophagy exacerbated neuronal apoptosis worsened neurological outcomes, and nullified the neuroprotective effects of nimodipine in the SAH mouse model. These findings highlight a mechanism where SIRT3 mediates nimodipine's neuroprotective effects by regulating mitochondrial function and autophagy. This suggests that SIRT3 serves as a promising therapeutic target for SAH.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 2","pages":"46"},"PeriodicalIF":3.4,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The multifaceted roles of aldolase A in cancer: glycolysis, cytoskeleton, translation and beyond.","authors":"Shiyi Yu, Yaji Xue, Yongli Chen, Yuanye Cao, Yawen Yang, Xiaoyu Ge, Xinting Cai","doi":"10.1007/s13577-025-01172-4","DOIUrl":"https://doi.org/10.1007/s13577-025-01172-4","url":null,"abstract":"<p><p>Cancer, a complicated disease characterized by aberrant cellular metabolism, has emerged as a formidable global health challenge. Since the discovery of abnormal aldolase A (ALDOA) expression in liver cancer for the first time, its overexpression has been identified in numerous cancers, including colorectal cancer (CRC), breast cancer (BC), cervical adenocarcinoma (CAC), non-small cell lung cancer (NSCLC), gastric cancer (GC), hepatocellular carcinoma (HCC), pancreatic cancer adenocarcinoma (PDAC), and clear cell renal cell carcinoma (ccRCC). Moreover, ALDOA overexpression promotes cancer cell proliferation, invasion, migration, and drug resistance, and is closely related to poor prognosis of patients with cancer. Although originally discovered to promote cancer initiation and progression by accelerating glycolysis, recent studies have revealed its atypical roles in cancer, e.g., adjusting cytoskeleton, regulating mRNA translation, cell signaling pathways, and DNA repair. These aforementioned findings challenge our traditional understanding of ALDOA function and prompt deep exploration of its novel roles in tumor biology. The present review summarizes the latest insights into ALDOA as a potential cancer biomarker and therapeutic target.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 2","pages":"45"},"PeriodicalIF":3.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory effects of the combination of rapamycin with gemcitabine plus paclitaxel on the growth of pancreatic cancer tumors.","authors":"Yuri Jobu, Miki Nishigawa, Kaoru Furihata, Mutsuo Furihata, Kazushige Uchida, Keisuke Taniuchi","doi":"10.1007/s13577-024-01165-9","DOIUrl":"10.1007/s13577-024-01165-9","url":null,"abstract":"<p><p>We previously examined the antitumor effects of short interfering RNA nanoparticles targeting mammalian target of rapamycin (mTOR) in an orthotopic pancreatic cancer mouse model. We herein report the inhibitory effects of the mTOR inhibitor rapamycin on tumor growth in a novel established mouse model of pancreatic cancer using human pancreatic cancer cell line-derived organoids. Gemcitabine, 5-fluorouracil, and gemcitabine plus nab-paclitaxel are clinically used to treat advanced pancreatic cancer. In vitro assays showed that rapamycin strongly inhibited cell invasion, while gemcitabine, 5-fluorouracil, and gemcitabine plus paclitaxel primarily inhibited cell proliferation with minimal effects on invasion. In vivo mouse experiments demonstrated that rapamycin exhibited superior antitumor activity to S-1 (a metabolically activated prodrug of 5-fluorouracil) and another mTOR inhibitor, everolimus, while its efficacy was similar to that of gemcitabine plus paclitaxel (which was used instead of nab-paclitaxel due to concerns about allergic reactions in mice to human albumin) in a mouse model of pancreatic cancer using human pancreatic cancer cell line-derived organoids. Furthermore, the combination of rapamycin with gemcitabine plus paclitaxel exerted synergistic inhibitory effects on the growth of pancreatic cancer tumors. Although the inhibition of tumor growth was significantly stronger in everolimus-treated mice than in control mice, there were no additive anti-growth effects when combined with gemcitabine plus paclitaxel. The present results suggest that the combination of rapamycin with gemcitabine plus paclitaxel achieved the greatest reduction in tumor volumes in the mouse xenograft model and, thus, has significant clinical promise.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 2","pages":"44"},"PeriodicalIF":3.4,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11723851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142966795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High glucose induces renal tubular epithelial cell senescence by inhibiting autophagic flux.","authors":"Ying Zhang, Yu Zhao, Yu-Qiu Liu, Ya-Ping Fang, Li Sun, Shan-Zhai Wei, Xiao-Dong Zhu, Xiao-Liang Zhang","doi":"10.1007/s13577-024-01156-w","DOIUrl":"https://doi.org/10.1007/s13577-024-01156-w","url":null,"abstract":"<p><p>Autophagy, a cellular degradation process involving the formation and clearance of autophagosomes, is mediated by autophagic proteins, such as microtubule-associated protein 1 light chain 3 (LC3) and sequestosome 1 (p62), and modulated by 3-methyladenine (3-MA) as well as chloroquine (CQ). Senescence, characterised by permanent cell cycle arrest, is marked by proteins such as cyclin-dependent kinase inhibitor 1 (p21) and tumour protein 53 (p53). This study aims to investigate the relationship between cell senescence and renal function in diabetic kidney disease (DKD) and the effect of autophagy on high-glucose-induced cell senescence. We categorised 46 patients with DKD diagnosed by renal biopsy into classes I, IIa, IIb, III and IV and used four normal kidney specimens from patients with renal trauma as controls. We evaluated pathological changes, LC3 and p21. We used streptozotocin-induced DKD models in rats and 35 mM glucose-cultured human proximal tubular epithelial cells (HK-2) with or without 3-MA and CQ. We assessed p53, p21, LC3 and p62. We observed autophagosomes and detected senescence-associated galactosidase (SA-β-gal) activity. In patients with DKD, p21 and LC3 expression levels increased over time and correlated positively with blood creatinine and proteinuria. In DKD rats and HK-2 cells, p21, p53, LC3 and p62 expression levels were higher than in the controls, as were SA-β-gal-positive cells, renal tubular autophagosomes and co-expression of p21 and LC3. The 3-MA reduced p16, p21 and p53 expression compared with the high glucose group, whereas CQ had the opposite effect. These results suggest that renal tubular cell senescence is associated with the progression of DKD. Additionally, autophagic flux may play a role in mediating high-glucose-induced senescence in renal tubular cells.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 2","pages":"43"},"PeriodicalIF":3.4,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The dual role of PTPN22 in immune modulation and transplantation tolerance.","authors":"Beyza Goncu, Ali Osman Gurol","doi":"10.1007/s13577-024-01170-y","DOIUrl":"https://doi.org/10.1007/s13577-024-01170-y","url":null,"abstract":"","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 2","pages":"42"},"PeriodicalIF":3.4,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling the lymph node stromal cells in oral squamous cell carcinoma: insights into the stromal cues in nodal metastasis.","authors":"Bonney Lee James, Shaesta Naseem Zaidi, R K Aiswarya, Vivek Shetty, R Vidya Bhushan, Yogesh Dokhe, B S Naveen, Vijay Pillai, Sujan K Dhar, Moni Abraham Kuriakose, Amritha Suresh","doi":"10.1007/s13577-024-01166-8","DOIUrl":"https://doi.org/10.1007/s13577-024-01166-8","url":null,"abstract":"<p><p>The study explores the development and characterization of lymph node stromal cell cultures (LNSCs) from patients with oral squamous cell carcinoma (OSCC), highlighting the importance of understanding tumor-node cross-talk for effective prognostic and therapeutic interventions. Herein, we describe the development and characterization of primary lymph node stromal cells (LNSCs, N = 14) from nodes of metastatic and non-metastatic OSCC patients. Primary cultures were established by the explant method from positive (N + ; N = 2), and negative nodes (N0_m; N = 4) of the metastatic patients (N = 3) as well as negative (N0_nm; N = 8) nodes from non-metastatic (N = 4) patients. STR profiling confirmed the purity and novelty, while characterization by immunocytochemistry/flow cytometry revealed heterogeneous cell populations consisting of fibroblastic reticular cells (CD31-Gp38 +) and double negative cells (CD31-Gp38-). Transcriptomic profiling indicated molecular alterations in the cells based on the non-metastatic, the pre-metastatic or metastatic status of the nodes, pro-inflammatory, matrix remodeling, and immune evasion being the primary pathways. Assessment of the protein levels for five selected markers (MX1, ISG15, CPM, ITGB4 and FOS) in the cell lines revealed that CPM levels were significantly reduced in the N + and N0_m nodes whereas ISG15 levels reduced in N0_m. Significantly, the profiling also provided insights into possible glycosylation of CPM (N0_nm) and ISGylation of ISG15 (N0_m). Cytokine profiling indicated release of chemokines/anti-proliferative cytokines from the negative nodes, while angiogenic/pro-metastatic cytokines were released from the nodes of metastatic patients. The lymph node stromal cell models established in the study with distinctive transcriptomic/cytokine characteristics will be invaluable in delineating the processes underlying nodal metastasis.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 2","pages":"41"},"PeriodicalIF":3.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Title: Identification of a novel GRHPR mutation in primary hyperoxaluria type 2 and establishment of patient-derived iPSC line.","authors":"Xiang Yan, Zihao Xu, Yue Chen, Langping Gao, Zige Jiang, Lexin Liu, Guozhen Wang, Xiangjun Chen, Chengpeng Wu, Lidan Hu","doi":"10.1007/s13577-024-01169-5","DOIUrl":"10.1007/s13577-024-01169-5","url":null,"abstract":"<p><p>This research delves into Primary Hyperoxaluria Type 2 (PH2), an autosomal recessive disorder precipitated by a unique case of compound heterozygous deleterious mutations in the GRHPR gene, specifically the intron2/3 c.214-2 T > G and the exon8 c.864-865delTG, leading to a premature stop codon at p.Val289fsTer22. The intron 2/3 variant (c.214-2 T > G) is a novel finding and is reported for the first time. These mutations are associated with profound alterations in protein structure and function. Employing patient-derived induced pluripotent stem cells (iPSCs), we have successfully generated a patient-specific model that exhibits the hallmarks of pluripotency, including typical stem cell morphology, expression of pluripotency markers, and a normal karyotype. The iPSCs are capable of differentiating into all three germ layers, underscoring their potential for regenerative medicine. The established iPSC line offers a promising platform for drug screening and regenerative medicine approaches for PH2.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 2","pages":"40"},"PeriodicalIF":3.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human amniotic epithelial stem cells, a potential therapeutic approach for diabetes and its related complications.","authors":"Zhenshuo Chen, Yunfei Luo, Jianping Liu","doi":"10.1007/s13577-024-01171-x","DOIUrl":"10.1007/s13577-024-01171-x","url":null,"abstract":"<p><p>The escalating diabetes prevalence has heightened interest in innovative therapeutic strategies for this disease and its complications. Human amniotic epithelial stem cells (HAESCs), originate from the innermost layer of the placenta closest to the fetus and express stem cell markers in the amniotic membrane's umbilical cord attachment area, which have garnered significant attention. This article critically examines emerging research advancements and potential application values of hAESCs in treating diabetes and its complications. Initially, we will discuss the characteristics, origin, and advantages of hAESCs in differentiating into insulin-secreting cells. Subsequently, we will focus on the potential applications of hAESCs in treating diabetes complications such as diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy, etc. We will scrutinize the progress of relevant clinical studies and trials involving hAESC therapy. In conclusion, as an emerging diabetes treatment method, hAESCs exhibit immense potential and application value. Despite numerous challenges in practical application, we are confident that with scientific advancement and technological progress, hAESCs will play a pivotal role in treating diabetes and its related complications.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 2","pages":"39"},"PeriodicalIF":3.4,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}