Cell Biochemistry and Function最新文献

{"title":"Epigenetic Regulation by Histone Methylation and Demethylation in Freeze-Tolerant Frog Kidney","authors":"Olawale O. Taiwo,&nbsp;Sarah A. Breedon,&nbsp;Kenneth B. Storey","doi":"10.1002/cbf.70036","DOIUrl":"https://doi.org/10.1002/cbf.70036","url":null,"abstract":"<p>The wood frog (<i>Rana sylvatica</i>) endures whole-body freezing over the winter, with extensive extracellular ice formation and halted physiological activities. Epigenetic mechanisms, including reversible histone lysine methylation, enable quick alterations in gene expression, helping to maintain viability during freeze-thaw cycles. The present study evaluated eight histone lysine methyltransferases (KMTs), 10 histone lysine demethylases (KDMs), and 11 histone marks in wood frog kidneys. Using immunoblotting, significant changes in relative protein levels of multiple KMTs and KDMs were observed in response to freezing, with variable alterations during thawing. Specifically, the repressive methyl marks H3K27me1 and H4K20me3 significantly decreased during freezing, whereas H3K9me3, H3K27me3, and H3K36me2 decreased during thawing. These results demonstrate that the regulation of histone methylation and demethylation play crucial roles in controlling gene expression over the freeze-thaw cycle and the maintenance of normal renal physiology.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"42 8","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbf.70036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142868851","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":"Melatonin-Supplemented Obese Female Mice Show Less Inflammation in Ovarian Adipocytes and Browning in Subcutaneous Adipocytes","authors":"Brenda A. Nagagata,&nbsp;Carlos A. Mandarim-de-Lacerda,&nbsp;Marcia Barbosa Aguila","doi":"10.1002/cbf.70034","DOIUrl":"https://doi.org/10.1002/cbf.70034","url":null,"abstract":"<div>\u0000 \u0000 <p>We hypothesized that melatonin (Mel) supplementation may offer therapeutic benefits for obesity, particularly in women. Therefore, the study evaluated Mel's effects on white adipose tissue (WAT) in diet-induced obese female mice. Four-week-old C57BL/6 females were assigned to either a control diet (C group) or a high-fat diet (HF group) for 6 weeks (<i>n</i> = 20/group). Following this, Mel was administered (10 mg/kg/day) for 8 weeks (<i>n</i> = 10/group), resulting in four groups: C, CMel, HF, and HFMel. The HF group developed obesity. HFMel displayed reduced fat pad size, lower plasma insulin, and improved glucose tolerance and insulin resistance compared to HF. In ovarian WAT (oWAT), HFMel versus HF showed reduced pro-inflammatory markers, less endoplasmic reticulum (ER) stress, and smaller adipocyte size. In subcutaneous WAT (sWAT), HFMel versus HF demonstrated increased adipocyte multiloculation, higher uncoupling protein-1 expression, and elevated thermogenic gene expression. Principal component analysis of gene expressions in oWAT and sWAT revealed significant differences: in oWAT, ER stress and inflammation markers were linked to the HF group, while HFMel and CMel clustered together, indicating a beneficial Mel effect. In sWAT, HFMel and CMel clustered on the opposite side of HF, which is associated with thermogenic gene expressions. In conclusion, the findings demonstrate that Mel supplementation in obese female mice, even when maintained on an HF diet, effectively modulated weight gain and reduced ovarian and subcutaneous fat accumulation. Mel supplementation positively influenced insulin resistance, inflammation, and ER stress while promoting thermogenesis in WAT in obese female mice.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"42 8","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142868850","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":"Biotechnological Interventions for the Production of Subunit Vaccines Against Group A Rotavirus","authors":"Mukta Prajapati,&nbsp;Pooja Malik,&nbsp;Astha Sinha,&nbsp;Honey Yadav,&nbsp;Yachna K. Jaiwal,&nbsp;Yogesh K. Ahlawat,&nbsp;Darshna Chaudhary,&nbsp;Ranjana Jaiwal,&nbsp;Nisha Sharma,&nbsp;Pawan K. Jaiwal,&nbsp;Vijay K. Chattu","doi":"10.1002/cbf.70031","DOIUrl":"https://doi.org/10.1002/cbf.70031","url":null,"abstract":"<p>Group A rotavirus (RVA) is a major cause of severe gastroenteritis in infants and young children globally, despite the availability of live-attenuated vaccines. Challenges such as limited efficacy in low-income regions, safety concerns for immunocompromised individuals, and cold-chain dependency necessitate alternative vaccine strategies. Subunit vaccines, which use specific viral proteins to elicit immunity, provide a safer and more adaptable approach. This review highlights biotechnological advancements in producing subunit vaccines, focusing on recombinant expression systems like bacterial, yeast, insect, mammalian, and plant-based platforms for scalable and cost-effective production of viral proteins. Key innovations include molecular engineering, adjuvant development, and delivery system improvements to enhance vaccine immunogenicity and efficacy. Subunit vaccines and virus-like particles expressed in various systems have demonstrated promising preclinical and clinical results, with some candidates nearing commercial readiness. Reverse vaccinology, combined with Artificial Intelligence and Machine Learning, is driving the development of innovative multiepitope vaccines and antivirals. Strategies such as passive immunization, single-chain antibodies, immunobiotics, and novel antivirals are also explored as alternative management options. The review also underscores advanced genome editing and reverse genetics approaches to improve vaccine design and antiviral therapies. These biotechnological interventions offer hope for equitable and effective control of rotavirus diarrhea, particularly in resource-limited settings, and represent significant progress toward addressing current vaccine limitations.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"42 8","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbf.70031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142868766","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":"Effectiveness of a Novel PLA2R1 Knock-in Middle Age Rat Model in Repairing Renal Function Damage","authors":"Daihe Yang,&nbsp;Zitong Zhang,&nbsp;Lu Zhao,&nbsp;Wendong Sui,&nbsp;Yinyin Li,&nbsp;Yun Zhou,&nbsp;Bo Huang","doi":"10.1002/cbf.70032","DOIUrl":"10.1002/cbf.70032","url":null,"abstract":"<div>\u0000 \u0000 <p>Phospholipase A2 receptor 1 (PLA2R1) exists important role in membranous nephropathy. In this study, we evaluate a PLA2R1 in a middle-aged rat model of renal function repair to further investigate the molecular mechanisms of membranous nephropathy. We analyzed the PLA2R1 knockout (KO) model and PLA2R1 knock in (KI) model in rats, extending the time to 85 weeks of age. Urinary biochemical indicators were detected using a fully automated biochemical analyzer. The complement C3, IgG, and Nephrin were detected using the immunofluorescence method. Western blot was used to detect the expression levels of complement C3, IgA and PLA2R1 in middle-aged models. The KO model continues to display glomerular proteinuria, complement C3 aggregation, and IgA and IgG deposition. Comparing with the KO model, the deposition of complement C3 and IgA in the glomerulus of the KI chimeric model still exists and IgG expression weakened. Inserting humanized PLA2R1 into rats can continuously repair partial renal function and reduce proteinuria, which will help investigate the pathogenesis of membranous nephropathy and complement activation signaling pathways.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"42 8","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863518","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":"Effect of Aconitum diphtheria on the Proliferation, Apoptosis, and Inflammatory Response of Rheumatoid Arthritis Fibroblast-Like Synoviocytes","authors":"Yan Meng,&nbsp;Xuan-lin Cai,&nbsp;Shan Cong,&nbsp;Jiao Sun,&nbsp;Yong-wei Hu,&nbsp;Li Luo","doi":"10.1002/cbf.70026","DOIUrl":"10.1002/cbf.70026","url":null,"abstract":"<div>\u0000 \u0000 <p>Rheumatoid arthritis (RA), a highly disabling autoimmune disease, is characterized by joint damage and synovial hyperplasia. This paper was designed to explore the effect and mechanisms of <i>Aconitum diphtheria</i> on the proliferation and apoptosis of RA fibroblast-like synoviocytes (RA-FLS). First, RA-FLS was treated with different doses of <i>A. diphtheria</i> extracts. Then, an inverted biological microscope was adopted to observe the RA-FLS morphology. Subsequently, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining, Cell Counting Kit-8 and western blot were utilized to analyze the apoptosis, proliferation, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway-related proteins in RA-FLS, respectively. The experimental results disclosed that, after treatment of RA-FLS with <i>A. diphtheria</i> extracts, the cells became round and the intercellular space was increased. Besides, the RA-FLS proliferation was effectively inhibited by <i>A. diphtheria</i> extracts, while the apoptosis was promoted. Additionally, <i>A. diphtheria</i> extracts could effectively downregulate the expression levels of p-NF-κB (p50), NF-κB (p50), p-NF-κB (p65), and NF-κB (p65). Collectively, <i>A. diphtheria</i> can effectively inhibit RA-FLS proliferation and promote apoptosis in a dose-dependent manner. Similarly, <i>A. diphtheria</i> is able to downregulate p-NF-κB and NF-κB protein expression, but there is no dose–response relationship.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"42 8","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833365","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":"Synergistic Effect of Donepezil and Neurotropic B Vitamins on Dysregulated Antioxidant, Inflammation and Neurotransmitter Status in Aluminium Chloride-Induced Neurotoxicity in Rats","authors":"Bidemi Emmanuel Ekundayo,&nbsp;Olusola Bolaji Adewale,&nbsp;Blessing Ariyo Obafemi,&nbsp;Monde McMillan Ntwasa,&nbsp;Sogolo Lucky Lebelo,&nbsp;Tajudeen Olabisi Obafemi","doi":"10.1002/cbf.70028","DOIUrl":"10.1002/cbf.70028","url":null,"abstract":"<div>\u0000 \u0000 <p>Combination therapy offers a promising advantage because they target multiple pathways involved in the pathogenesis and progression of Alzheimer's disease. This study aimed to investigate the synergistic effect of donepezil and each of vitamin B12, vitamin B6 and vitamin B1 on aluminium chloride (AlCl₃)-induced neurotoxicity in rats. Fifty-four rats were divided into nine groups of six. Group I received distilled water, group II—AlCl₃ (100 mg/kg), group III- AlCl₃ (100 mg/kg) + Donepezil (10 mg/kg), group IV-AlCl₃(100 mg/kg) + Donepezil (10 mg/kg) + Vitamin B12 (5 mg/kg), group V-AlCl₃ (100 mg/kg) + Donepezil (10 mg/kg) + Vitamin B6 (5 mg/kg), group VI-AlCl₃ (100 mg/kg) + Donepezil (10 mg/kg) + Vitamin B1 (5 mg/kg), group VII-AlCl₃ (100 mg/kg) + Vitamin B12 (5 mg/kg), group VIII-AlCl₃ (100 mg/kg) + Vitamin B6 (5 mg/kg), group IX-AlCl₃ (100 mg/kg) + Vitamin B1 (5 mg/kg). Treatment lasted for 40 days. Biochemical analyses of the brain revealed that chronic administration of AlCl₃ significantly increased the level of inflammatory cytokines, caspase 9, malondialdehyde, nitric oxide and acetylcholinesterase (AChE) activity, while causing a significant decrease in superoxide dismutase (SOD) activity, Nrf2, reduced glutathione, dopamine and norepinephrine. Results also showed that AlCl₃ caused cognitive impairment as indicated by a reduction in the percentage alternation index and hypo-activity towards novel object in animals treated with AlCl₃ only. Moreover, results from biochemical evaluations indicated that treatment with donepezil, B vitamins and combination of donepezil and B vitamins attenuated the deficits in dopamine, norepinephrine, Nrf2, SOD and reduced glutathione, while also reducing the elevated levels of malondialdehyde, nitric oxide, AChE, caspase 9 and inflammatory markers. These observations were corroborated by result of histopathological evaluation. The combination of donepezil and vitamin B12, B6 and B1 proved to be more effective than donepezil monotherapy. Donepezil conferred significant protection against AlCl₃–induced neurotoxicity, however, the combination of donepezil and vitamin B12, vitamin B6 and Vitamin B1 significantly performed better in neuroprotective indices than donepezil monotherapy. The combination of donepezil and vitamin B1 was better amongst the three combination therapies in this study.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"42 8","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827541","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":"Thymol as Biofilm and Efflux Pump Inhibitor: A Dual-Action Approach to Combat Mycobacterium tuberculosis","authors":"Bhabani Shankar Das,&nbsp;Ashirbad Sarangi,&nbsp;Isha Pahuja,&nbsp;Vishal Singh,&nbsp;Suvendu Ojha,&nbsp;Sidhartha Giri,&nbsp;Ashima Bhaskar,&nbsp;Debapriya Bhattacharya","doi":"10.1002/cbf.70030","DOIUrl":"10.1002/cbf.70030","url":null,"abstract":"<div>\u0000 \u0000 <p>Tuberculosis (TB) remains a significant global health challenge, exacerbated by the emergence of drug-resistant strains of <i>Mycobacterium tuberculosis</i> (<i>M. tb</i>). The complex biology of <i>M. tb</i>, particularly its key porins, contributes to its resilience against conventional treatments, highlighting the exploration of innovative therapeutic strategies. Following with this challenges, the present study investigates the bioactivity properties of phenolic compounds derived from the terpene groups, specifically through Thymol (THY) against <i>M. smegmatis</i> as a surrogated model fo<i>r M. tb</i>. Furthermore, the study employed with combination of two approaches i.e., in vitro assays and computational methods to evaluate the efficacy of THY against <i>M. smegmatis</i> and its interaction with <i>M. tb</i> biofilm and efflux pump proteins, particularly Rv1258c and Rv0194. The in vitro findings demonstrated that THY exhibits inhibitory activity against <i>M. smegmatis</i> and shows promising interaction with a combination of isoniazid (INH) and rifampicin (RIF) of TB regimens. Furthermore, THY demonstrated significant inhibitory action towards motility and biofilm formation of <i>M. smegmatis</i>. The combination of THY with INH and RIF exhibited a synergistic effect, enhancing the overall antimicrobial efficacy. Additionally, THY displayed reactive oxygen species (ROS) activity and potential efflux pump inhibitory action towards <i>M. smegmatis</i>. The computational analysis revealed that THY interacts effectively with efflux pump proteins Rv1258c and Rv0194, showing superior binding affinity compared to verapamil, a known efflux pump inhibitor. Pharmacokinetic studies highlighted that THY possess a favourable safety profile. In conclusion, THY represents a promising inhibitory compound for tuberculosis prevention, potentially addressing challenges posed by drug resistance.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"42 8","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827542","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":"Harnessing Bioluminescence: A Comprehensive Review of In Vivo Imaging for Disease Monitoring and Therapeutic Intervention","authors":"B. Sangeetha,&nbsp;K. I. Leroy,&nbsp;B. Udaya Kumar","doi":"10.1002/cbf.70020","DOIUrl":"10.1002/cbf.70020","url":null,"abstract":"<div>\u0000 \u0000 <p>The technique of using naturally occurring light-emitting reactants (photoproteins and luciferases] that have been extracted from a wide range of animals is known as bioluminescence imaging, or BLI. This imaging offers important details on the location and functional state of regenerative cells inserted into various disease-modeling animals. Reports on gene expression patterns, cell motions, and even the actions of individual biomolecules in whole tissues and live animals have all been made possible by bioluminescence. Generally speaking, bioluminescent light in animals may be found down to a few centimetres, while the precise limit depends on the signal's brightness and the detector's sensitivity. We can now spatiotemporally visualize cell behaviors in any body region of a living animal in a time frame process, including proliferation, apoptosis, migration, and immunological responses, thanks to BLI. The biological applications of in vivo BLI in nondestructively monitoring biological processes in intact small animal models are reviewed in this work, along with some of the advancements that will make BLI a more versatile molecular imaging tool.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"42 8","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823919","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":"Exploring the Function of OPTN From Multiple Dimensions","authors":"Yanan Guo,&nbsp;Yixiao Tian,&nbsp;Peng Xia,&nbsp;Xinyue Zhou,&nbsp;Xiaohui Hu,&nbsp;Zhao Guo,&nbsp;Pengfei Ji,&nbsp;Xinyi Yuan,&nbsp;Daosen Fu,&nbsp;Keyu Yin,&nbsp;Rong Shen,&nbsp;Degui Wang","doi":"10.1002/cbf.70029","DOIUrl":"10.1002/cbf.70029","url":null,"abstract":"<div>\u0000 \u0000 <p>Autophagy is an essential intracellular degradation system responsible for delivering cytoplasmic components to lysosomes. Within this intricate process, optineurin (OPTN), an autophagy receptor, has attracted extensive attention due to its multifaceted roles in the autophagy process. OPTN is regulated by various posttranslational modifications and actively participates in numerous signaling pathways and cellular processes. By exploring the regulatory mechanism of OPTN posttranslational modification, we can further understand the critical role of protein posttranslational modification in biological progress, such as autophagy. Additionally, OPTN is implicated in many human diseases, including rheumatoid arthritis, osteoporosis, and infectious diseases. And we delve into the inflammatory pathways regulated by OPTN and clarify how it regulates inflammatory diseases and cancer. We aim to enhance the understanding of OPTN's multifaceted functions in cellular processes and its implications in the pathogenesis of inflammatory diseases and cancer.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"42 8","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817241","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":"Impact of Tissue Factor Gene Knockout on Coagulation Properties of Umbilical Cord-Derived Multipotent Mesenchymal Stromal/Stem Cells","authors":"Zahra Heidari,&nbsp;Jafar Fallahi,&nbsp;Mohsen Sisakht,&nbsp;Fatemeh Safari,&nbsp;Kamran Hosseini,&nbsp;Ardeshir Bahmanimehr,&nbsp;Amir Savardashtaki,&nbsp;Sahar Khajeh,&nbsp;Seyed Mohammad Bagher Tabei,&nbsp;Vahid Razban","doi":"10.1002/cbf.70021","DOIUrl":"10.1002/cbf.70021","url":null,"abstract":"<div>\u0000 \u0000 <p>Multipotent mesenchymal stromal/stem cells (MSCs) refer to a population of stem cells that exhibit distinct progenitor cell characteristics including the potential for differentiation into a wide range of cell types. MSCs have become a promising candidate for cell therapy and tissue regeneration due to their unique properties, such as their ability to differentiate into multiple cell types, their capacity for expansion, self-renewal, and immune-regulatory effects. However, reports have brought attention to thrombosis-related complications associated with MSCs therapy in the last decade. As tissue factor (TF) is a powerful coagulation activator expressed by MSCs that stimulates the extrinsic coagulation pathway, we investigated the thrombotic properties of human umbilical cord MSCs (HUCMSCs) after knocking out the <i>TF</i> gene. MSCs populations that obtained from umbilical cord were cultured and expanded in the appropriate medium cell culture. The identity of the MSCs was verified through flow cytometry, and their ability to differentiate into osteogenic and adipogenic lineages. Two gRNAs for Exons 1 and 2 of the <i>TF</i> gene have been designed and cloned into px458 vector's backbone (pSpCas9 (BB)−2A-GFP). Following transfecting of gRNAs into HUCMSCs and successfully knocking out the <i>TF</i> gene using GAP-PCR, the impact of normal and knockout HUCMSCs on coagulation was assessed through prothrombin time (PT), <span>D</span>-dimer level, clotting time (CT), and turbidity assay. Furthermore, the impact of TF knockout (TFKO) on MMP19 expression was assessed. Our results revealed that the PT was prolonged and <span>D</span>-dimer level was decreased in TFKO group compared to normal HUCMSCs. These findings suggest that <i>TF</i> gene plays a crucial role in regulating coagulation in HUCMSCs. Also, a significant reduction in MMP19 expression was observed within the TFKO group.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"42 8","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806193","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}