Human Cell最新文献_第7页

Single-cell sequencing advances in research on mesenchymal stem/stromal cells. 单细胞测序在间充质干细胞/基质细胞研究中的进展。

IF 3.4 3区生物学

Human Cell Pub Date : 2024-07-01 Epub Date: 2024-05-14 DOI: 10.1007/s13577-024-01076-9

Qingxi Long, Pingshu Zhang, Ya Ou, Wen Li, Qi Yan, Xiaodong Yuan

{"title":"Single-cell sequencing advances in research on mesenchymal stem/stromal cells.","authors":"Qingxi Long, Pingshu Zhang, Ya Ou, Wen Li, Qi Yan, Xiaodong Yuan","doi":"10.1007/s13577-024-01076-9","DOIUrl":"10.1007/s13577-024-01076-9","url":null,"abstract":"Mesenchymal stem/stromal cells (MSCs), originating from the mesoderm, represent a multifunctional stem cell population capable of differentiating into diverse cell types and exhibiting a wide range of biological functions. Despite more than half a century of research, MSCs continue to be among the most extensively studied cell types in clinical research projects globally. However, their significant heterogeneity and phenotypic instability have significantly hindered their exploration and application. Single-cell sequencing technology emerges as a powerful tool to address these challenges, offering precise dissection of complex cellular samples. It uncovers the genetic structure and gene expression status of individual contained cells on a massive scale and reveals the heterogeneity among these cells. It links the molecular characteristics of MSCs with their clinical applications, contributing to the advancement of regenerative medicine. With the development and cost reduction of single-cell analysis techniques, sequencing technology is now widely applied in fundamental research and clinical trials. This study aimed to review the application of single-cell sequencing in MSC research and assess its prospects.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923498","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}

引用次数: 0

VBP1 promotes tumor proliferation as a part of the hypoxia-related signature in esophageal squamous cell carcinoma. VBP1 促进肿瘤增殖，是食管鳞状细胞癌缺氧相关特征的一部分。

IF 3.4 3区生物学

Human Cell Pub Date : 2024-07-01 Epub Date: 2024-05-03 DOI: 10.1007/s13577-024-01068-9

Huikai Miao, Wuyou Gao, Leqi Zhong, Hongmu Li, Dongni Chen, Chunmei Xu, Zhesheng Wen, Youfang Chen

{"title":"VBP1 promotes tumor proliferation as a part of the hypoxia-related signature in esophageal squamous cell carcinoma.","authors":"Huikai Miao, Wuyou Gao, Leqi Zhong, Hongmu Li, Dongni Chen, Chunmei Xu, Zhesheng Wen, Youfang Chen","doi":"10.1007/s13577-024-01068-9","DOIUrl":"10.1007/s13577-024-01068-9","url":null,"abstract":"Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor in East Asia. Hypoxia, a hallmark of solid tumors, significantly alters redox homeostasis inside tumor microenvironment. This alteration drives tumor proliferation, invasion, and metastasis, leading to poor prognostic outcomes. However, the role of hypoxia-related genes in ESCC remains poorly understood. We employed RNA sequencing to identify differentially expressed genes in ESCC. Clinical data, transcriptome profiles, and a hypoxia-related gene set were extracted from open-source databases. A prognostic model was constructed using least absolute shrinkage and selection operator (LASSO) regression, which was then validated through Cox regression analysis. Within this prognostic model, we pinpointed and investigated a key hypoxia-related gene affecting prognosis. The gene's expression was validated using real-time PCR and immunohistochemistry in both esophageal carcinoma and normal tissues. Tumor proliferation was examined through in vitro and in vivo assays, including the Cell Counting Kit-8, EdU, colony formation, and subcutaneous tumor models. A robust four-gene prognostic model (VBP1, BGN, CDKN1A, and PPFIA1) was successfully constructed and validated. Among these, VBP1 emerged as a key gene, exhibiting high expression levels that correlated with poor prognosis in ESCC. Functional experiments confirmed that VBP1 significantly accelerated tumor proliferation both in vitro and in vivo. VBP1 is identified as a pivotal gene within the hypoxia-related prognostic signature, and it significantly promotes tumor proliferation in ESCC.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11194215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861110","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}

引用次数: 0

DNMT1 driven by mouse amniotic fluid mesenchymal stem cell exosomes improved corneal cryoinjury via inducing microRNA-33 promoter DNA hypermethylation modification in corneal epithelium cells. 小鼠羊水间充质干细胞外泌体驱动的DNMT1通过诱导角膜上皮细胞microRNA-33启动子DNA高甲基化修饰改善角膜冷冻损伤。

IF 3.4 3区生物学

Human Cell Pub Date : 2024-07-01 Epub Date: 2024-05-23 DOI: 10.1007/s13577-024-01082-x

Weiqi Xu, Xinfeng Fei, Zeyu Cui, Dikang Pan, Yan Liu, Te Liu

{"title":"DNMT1 driven by mouse amniotic fluid mesenchymal stem cell exosomes improved corneal cryoinjury via inducing microRNA-33 promoter DNA hypermethylation modification in corneal epithelium cells.","authors":"Weiqi Xu, Xinfeng Fei, Zeyu Cui, Dikang Pan, Yan Liu, Te Liu","doi":"10.1007/s13577-024-01082-x","DOIUrl":"10.1007/s13577-024-01082-x","url":null,"abstract":"Severe corneal cryoinjury can cause permanent corneal swelling and bullous keratopathy, one of the main reason for loss of sight. Mouse amniotic fluid mesenchymal stem cells (mAF-MSCs) can repair corneal damage caused by freezing; however, whether the exosomes derived from mAF-MSCs have the same repair effect is unknown. In this study, the mAF-MSC-exosomes were transplanted into the eyeballs of corneal cryoinjured mice. Histopathological examination showed that the mAF-MSC-exosomes improved the corneal structure and status of corneal epithelial cells in corneal cryoinjured mice. RRBS-sequencing showed that compared with the control group, four genes (Rpl13-ps6, miR-33, Hymai, and Plagl1), underwent DNA hypermethylation modification after mAF-MSC-exosomes treatment. The result of FISH indicated that miR-33-3p hybridization signals were enhanced in corneal epithelial cells from mice treated with mAF-MSC-exosomes. Semi-quantitative PCR and western blotting indicated that mAF-MSC-exosomes contained high levels of DNMT1 mRNA and protein. Additionally, luciferase report assays indicated that miR-33-3p overexpression in NIH-3T3 mouse embryonic fibroblast cells inhibited the activity of luciferase carrying a sequence from the 3' untranslated region of Bcl6. Moreover, BCL6 mRNA and protein levels in corneal tissues from mice treated with mAF-MSC-exosomes were higher than those in the control group. Therefore, our results suggested that mAF-MSC-exosomes could repair corneal cryoinjury by releasing DNMT1, which induced hypermethylation of the miR-33 promoter in corneal epithelial cells. Consequent downregulated miR-33 transcription upregulated Bcl6 expression, ultimately achieving the repair of corneal cryoinjury in mice.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089213","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}

引用次数: 0

Tyndallized bacteria prime bronchial epithelial cells to mount an effective innate immune response against infections. 胫骨化细菌能激发支气管上皮细胞对感染做出有效的先天性免疫反应。

IF 3.4 3区生物学

Human Cell Pub Date : 2024-07-01 Epub Date: 2024-05-30 DOI: 10.1007/s13577-024-01080-z

Serena Di Vincenzo, Caterina Di Sano, Claudia D'Anna, Maria Ferraro, Velia Malizia, Andreina Bruno, Marta Cristaldi, Chiara Cipollina, Valentina Lazzara, Paola Pinto, Stefania La Grutta, Elisabetta Pace

{"title":"Tyndallized bacteria prime bronchial epithelial cells to mount an effective innate immune response against infections.","authors":"Serena Di Vincenzo, Caterina Di Sano, Claudia D'Anna, Maria Ferraro, Velia Malizia, Andreina Bruno, Marta Cristaldi, Chiara Cipollina, Valentina Lazzara, Paola Pinto, Stefania La Grutta, Elisabetta Pace","doi":"10.1007/s13577-024-01080-z","DOIUrl":"10.1007/s13577-024-01080-z","url":null,"abstract":"Airway epithelium represents a physical barrier against toxic substances and pathogens but also presents pattern recognition receptors on the epithelial cells that detect pathogens leading to molecule release and sending signals that activate both the innate and adaptive immune responses. Thus, impaired airway epithelial function and poor integrity may increase the recurrence of infections. Probiotic use in respiratory diseases as adjuvant of traditional therapy is increasingly widespread. There is growing interest in the use of non-viable heat-killed bacteria, such as tyndallized bacteria (TB), due to safety concerns and to their immunomodulatory properties. This study explores in vitro the effects of a TB blend on the immune activation of airway epithelium. 16HBE bronchial epithelial cells were exposed to different concentrations of TB. Cell viability, TB internalization, TLR2 expression, IL-6, IL-8 and TGF-βl expression/release, E-cadherin expression and wound healing were assessed. We found that TB were tolerated, internalized, increased TLR2, E-cadherin expression, IL-6 release and wound healing but decreased both IL-8 and TGF-βl release. In conclusion, TB activate TLR2 pathway without inducing a relevant pro-inflammatory response and improve barrier function, leading to the concept that TB preserve epithelial homeostasis and could be used as strategy to prevent and to manage respiratory infection, exacerbations included.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11194193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176607","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}

引用次数: 0

PMAIP1 regulates autophagy in osteoblasts via the AMPK/mTOR pathway in osteoporosis. 在骨质疏松症中，PMAIP1 通过 AMPK/mTOR 通路调节成骨细胞的自噬。

IF 3.4 3区生物学

Human Cell Pub Date : 2024-07-01 Epub Date: 2024-04-30 DOI: 10.1007/s13577-024-01067-w

Yijie Gao, Anquan Huang, Yantao Zhao, Yunxia Du

{"title":"PMAIP1 regulates autophagy in osteoblasts via the AMPK/mTOR pathway in osteoporosis.","authors":"Yijie Gao, Anquan Huang, Yantao Zhao, Yunxia Du","doi":"10.1007/s13577-024-01067-w","DOIUrl":"10.1007/s13577-024-01067-w","url":null,"abstract":"Osteoporosis (OP) is a highly prevalent disorder characterized by low bone mass that severely reduces patient quality of life. Although numerous treatments for OP have been introduced in clinic, many have side effects and high costs. Therefore, there is still an unmet need for optimal solutions. Here, raw signal analysis was used to identify potential high-risk factors for OP, and the biological functions and possible mechanisms of action (MOAs) of these factors were explored via gene set enrichment analysis (GSEA). Subsequently, molecular biological experiments were performed to verify and analyze the discovered risk factors in vitro and in vivo. PMAIP1 was identified as a potential risk factor for OP and significantly suppressed autophagy in osteoblasts via the AMPK/mTOR pathway, thereby inhibiting the proliferation and differentiation of osteoblasts. Furthermore, we constructed an ovariectomy (OVX) model of OP in rats and simultaneously applied si-PMAIP1 for in vivo interference. si-PMAIP1 upregulated the expression of LC3B and p-AMPK and downregulated the expression of p-mTOR, and these effects were reversed by the autophagy inhibitor. Micro-CT revealed that, si-PMAIP1 significantly inhibited the development of osteoporosis in OVX model rats, and this therapeutic effect was attenuated by treatment with an autophagy inhibitor. This study explored the role and mechanism of PMAIP1 in OP and demonstrated that PMAIP1 may serve as a novel target for OP treatment.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870898","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}

引用次数: 0

Combined use of hydrogen-rich water and enzyme-digested edible bird's nest improves PMA/LPS-impaired wound healing in human inflammatory gingival tissue equivalents. 联合使用富氢水和酶消化燕窝可改善 PMA/LPS 对人类炎症牙龈组织等效创伤愈合的影响。

IF 3.4 3区生物学

Human Cell Pub Date : 2024-07-01 Epub Date: 2024-04-29 DOI: 10.1007/s13577-024-01065-y

Dongliang Wang, Naohiro Shimamura, Nobuhiko Miwa, Li Xiao

{"title":"Combined use of hydrogen-rich water and enzyme-digested edible bird's nest improves PMA/LPS-impaired wound healing in human inflammatory gingival tissue equivalents.","authors":"Dongliang Wang, Naohiro Shimamura, Nobuhiko Miwa, Li Xiao","doi":"10.1007/s13577-024-01065-y","DOIUrl":"10.1007/s13577-024-01065-y","url":null,"abstract":"Gingival wound healing plays a critical role in maintaining oral health. However, this process can be delayed by oxidative stress and excessive inflammatory responses. In this study, we established a human inflammatory gingival tissue equivalent (iGTE) to investigate the inhibitory effects of hydrogen-rich water (HW), enzyme-digested edible bird's nest (EBND) and sialic acid (SA) on PMA (an inducer of oxidative free radicals)- and LPS (an inflammatory stimulus)-impaired wound healing. The iGTE was constructed by human gingival fibroblasts (hGFs), keratinocytes and macrophages under three-dimensional conditions. Wounds in the iGTE and hGF/keratinocyte monolayers were created by mechanical injury. Tissues and cells were pretreated with HW, EBND, and SA, and then exposed to the inflammatory and oxidative environment induced by PMA (10 ng/mL) and LPS (250 ng/mL). The inflammatory cytokines IL-6 and IL-8 were quantitatively analyzed by ELISA. Histopathological image analysis was performed by HE and immunofluorescence staining. In the iGTE, PMA/LPS significantly reduced the epithelial thickness while causing a decrease in K8/18, E-cadherin, laminin and elastin expression and an increase in COX-2 expression along with ulcer-like lesions. In mechanically scratched hGFs and keratinocyte monolayers, PMA/LPS significantly impaired wound healing, and promoted the secretion of IL-6 and IL-8. Pretreatment of HW, EBND, and SA significantly suppressed PMA/LPS-induced wound healing delay and inflammatory responses in cell monolayers, as well as in the iGTE. Remarkably, the combined use of HW and EBND exhibited particularly robust results. Combined use of HW and EBND may be applied for the prevention and treatment of wound healing delay.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859247","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}

引用次数: 0

Aquaporins in colorectal cancer: exploring their role in tumorigenesis, metastasis, and drug response. 大肠癌中的水蒸发蛋白：探索它们在肿瘤发生、转移和药物反应中的作用。

IF 3.4 3区生物学

Human Cell Pub Date : 2024-07-01 Epub Date: 2024-05-29 DOI: 10.1007/s13577-024-01078-7

Maryam Azimi Mohammadabadi, Ali Moazzeni, Leila Jafarzadeh, Fatemeh Faraji, Amir Hossein Mansourabadi, Elahe Safari

{"title":"Aquaporins in colorectal cancer: exploring their role in tumorigenesis, metastasis, and drug response.","authors":"Maryam Azimi Mohammadabadi, Ali Moazzeni, Leila Jafarzadeh, Fatemeh Faraji, Amir Hossein Mansourabadi, Elahe Safari","doi":"10.1007/s13577-024-01078-7","DOIUrl":"10.1007/s13577-024-01078-7","url":null,"abstract":"Aquaporins (AQPs) are small, integral proteins facilitating water transport across plasma cell membranes in response to osmotic gradients. This family has 13 unique members (AQP0-12), which can also transport glycerol, urea, gases, and other salute small molecules. AQPs play a crucial role in the regulation of different cellular processes, including metabolism, migration, immunity, barrier function, and angiogenesis. These proteins are found to aberrantly overexpress in various cancers, including colorectal cancer (CRC). Growing evidence has explored AQPs as a potential diagnostic biomarker and therapeutic target in different cancers. However, there is no comprehensive review compiling the available information on the crucial role of AQPs in the context of colorectal cancer. This review highlights the significance of AQPs as the biomarker and regulator of tumor cells metabolism. In addition, the proliferation, angiogenesis, and metastasis of tumor cells related to AQPs expression as well as function are discussed. Understanding the AQPs prominent role in chemotherapy resistance is of great importance clinically.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161396","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}

引用次数: 0

CYTOR-NFAT1 feedback loop regulates epithelial-mesenchymal transition of retinal pigment epithelial cells. CYTOR-NFAT1反馈环调节视网膜色素上皮细胞的上皮-间质转化。

IF 3.4 3区生物学

Human Cell Pub Date : 2024-07-01 Epub Date: 2024-05-14 DOI: 10.1007/s13577-024-01075-w

Rong Zhang, Lin Wang, Yang Li, Yan Liu, Kui Dong, Yajing Pei, Junmei Zhao, Gang Liu, Jing Li, Xiaodan Zhang, Tong Cui, Yan Gao, Wenjuan Wang, Yongrui Wang, Chenwei Gui, Guohong Zhou

{"title":"CYTOR-NFAT1 feedback loop regulates epithelial-mesenchymal transition of retinal pigment epithelial cells.","authors":"Rong Zhang, Lin Wang, Yang Li, Yan Liu, Kui Dong, Yajing Pei, Junmei Zhao, Gang Liu, Jing Li, Xiaodan Zhang, Tong Cui, Yan Gao, Wenjuan Wang, Yongrui Wang, Chenwei Gui, Guohong Zhou","doi":"10.1007/s13577-024-01075-w","DOIUrl":"10.1007/s13577-024-01075-w","url":null,"abstract":"Epithelial mesenchymal transition (EMT) occurring in retinal pigment epithelial cells (RPE) is a crucial mechanism that contributes to the development of age-related macular degeneration (AMD), a pivotal factor leading to permanent vision impairment. Long non-coding RNAs (lncRNAs) have emerged as critical regulators orchestrating EMT in RPE cells. In this study, we explored the function of the lncRNA CYTOR (cytoskeleton regulator RNA) in EMT of RPE cells and its underlying mechanisms. Through weighted correlation network analysis, we identified CYTOR as an EMT-related lncRNA associated with AMD. Experimental validation revealed that CYTOR orchestrates TGF-β1-induced EMT, as well as proliferation and migration of ARPE-19 cells. Further investigation demonstrated the involvement of CYTOR in regulating the WNT5A/NFAT1 pathway and NFAT1 intranuclear translocation in the ARPE-19 cell EMT model. Mechanistically, CHIP, EMSA and dual luciferase reporter assays confirmed NFAT1's direct binding to CYTOR's promoter, promoting transcription. Reciprocally, CYTOR overexpression promoted NFAT1 expression, while NFAT1 overexpression increased CYTOR transcription. These findings highlight a mutual promotion between CYTOR and NFAT1, forming a positive feedback loop that triggers the EMT phenotype in ARPE-19 cells. These discoveries provide valuable insights into the molecular mechanisms of EMT and its association with AMD, offering potential avenues for targeted therapies in EMT-related conditions, including AMD.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923423","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}

引用次数: 0

Interrogating the estrogen-mediated regulation of adrenocortical Klotho expression using ovariectomized albino rat model exposed to repeated restraint stress. 利用暴露于反复束缚应激的卵巢切除白化大鼠模型，探讨雌激素介导的肾上腺皮质 Klotho 表达调控。

IF 3.4 3区生物学

Human Cell Pub Date : 2024-07-01 Epub Date: 2024-05-16 DOI: 10.1007/s13577-024-01069-8

Ahmed A Morsi, Ezat A Mersal, Ahmed M Abdelmoneim, Ghaiath Hussein, Mohamed M Sofii, Khalid Elfaki Ibrahim, Mohamed S Salim

{"title":"Interrogating the estrogen-mediated regulation of adrenocortical Klotho expression using ovariectomized albino rat model exposed to repeated restraint stress.","authors":"Ahmed A Morsi, Ezat A Mersal, Ahmed M Abdelmoneim, Ghaiath Hussein, Mohamed M Sofii, Khalid Elfaki Ibrahim, Mohamed S Salim","doi":"10.1007/s13577-024-01069-8","DOIUrl":"10.1007/s13577-024-01069-8","url":null,"abstract":"Reproductive aging is associated with altered stress response and many other menopausal symptoms. Little is known about the adrenal expression of the anti-aging protein Klotho or how it is modulated by estrogen in ovariectomized stressed rats. Fifty-six Wistar female rats were assigned into seven equal groups. Sham-operated (Sham), sham stressed (Sham/STS), ovariectomized (OVR), ovariectomized stressed (OVR/STS), ovariectomized stressed rosiglitazone-treated (OVR/STS/R), ovariectomized stressed estrogen-treated (OVR/STS/E), and ovariectomized stressed estrogen/GW9662 co-treated (OVR/STS/E/GW) groups. All stressed rats were subjected daily to a one-hour restraint stress test for 19 days. At the end of the experiment, blood was collected for serum corticosterone (CORT) analysis. Adrenal tissues were obtained and prepared for polymerase chain reaction (PCR) assay, hematoxylin and eosin (H&E), immunohistochemistry-based identification of Klotho and PPAR-γ, and Oil Red O (ORO) staining. The rise in serum CORT was negligible in the OVR/STS group, in contrast to the Sham/STS group. The limited CORT response in the former group was restored by estrogen and rosiglitazone and blocked by estrogen/GW9226 co-administration. ORO-staining revealed a more evident reduction in the adrenal fat in the OVR/STS group, which was reversed by estrogen and counteracted by GW. Also, there was a comparable expression pattern of Klotho and PPAR-γ in the adrenals. The adrenal Klotho decreased in the OVR/STS group, but was reversed by estrogen treatment. GW9226/estrogen co-treatment interfered with the regulatory effect of estrogen on Klotho. The study suggested modulation of the adrenal Kotho expression by estrogen, in the ovariectomized rats subjected to a restraint stress test. This estrogen-provided adrenal protection might be mediated by PPAR-γ activation.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140946318","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}

引用次数: 0

Generation of induced pluripotent stem cells from an individual with early onset and severe hypertrophic cardiomyopathy linked to MYBPC3: c.772G > A mutation. 从一名与 MYBPC3：c.772G > A 突变有关的早发性严重肥厚型心肌病患者体内生成诱导多能干细胞。

IF 3.4 3区生物学

Human Cell Pub Date : 2024-07-01 Epub Date: 2024-05-18 DOI: 10.1007/s13577-024-01073-y

Marta Ribeiro, Joanna Jager, Marta Furtado, Teresa Carvalho, Joaquim M S Cabral, Dulce Brito, Maria Carmo-Fonseca, Sandra Martins, Simão Teixeira da Rocha

{"title":"Generation of induced pluripotent stem cells from an individual with early onset and severe hypertrophic cardiomyopathy linked to MYBPC3: c.772G > A mutation.","authors":"Marta Ribeiro, Joanna Jager, Marta Furtado, Teresa Carvalho, Joaquim M S Cabral, Dulce Brito, Maria Carmo-Fonseca, Sandra Martins, Simão Teixeira da Rocha","doi":"10.1007/s13577-024-01073-y","DOIUrl":"10.1007/s13577-024-01073-y","url":null,"abstract":"Hypertrophic cardiomyopathy (HCM) is frequently caused by mutations in the MYPBC3 gene, which encodes the cardiac myosin-binding protein C (cMyBP-C). Most pathogenic variants in MYPBC3 are either nonsense mutations or result in frameshifts, suggesting that the primary disease mechanism involves reduced functional cMyBP-C protein levels within sarcomeres. However, a subset of MYPBC3 variants are missense mutations, and the molecular mechanisms underlying their pathogenicity remain elusive. Upon in vitro differentiation into cardiomyocytes, induced pluripotent stem cells (iPSCs) derived from HCM patients represent a valuable resource for disease modeling. In this study, we generated two iPSC lines from peripheral blood mononuclear cells (PBMCs) of a female with early onset and severe HCM linked to the MYBPC3: c.772G > A variant. Although this variant was initially classified as a missense mutation, recent studies indicate that it interferes with splicing and results in a frameshift. The generated iPSC lines exhibit a normal karyotype and display hallmark characteristics of pluripotency, including the ability to undergo trilineage differentiation. These novel iPSCs expand the existing repertoire of MYPBC3-mutated cell lines, broadening the spectrum of resources for exploring how diverse mutations induce HCM. They additionally offer a platform to study potential secondary genetic elements contributing to the pronounced disease severity observed in this individual.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11194200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960152","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}

引用次数: 0