JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献_第2页

LONP1 alleviates ageing-related renal fibrosis by maintaining mitochondrial homeostasis LONP1 通过维持线粒体稳态缓解与衰老相关的肾脏纤维化

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-09-11 DOI: 10.1111/jcmm.70090

Congxiao Zhang, Siman Shen, Li Xu, Man Li, Binyao Tian, Li Yao, Xinwang Zhu

{"title":"LONP1 alleviates ageing-related renal fibrosis by maintaining mitochondrial homeostasis","authors":"Congxiao Zhang, Siman Shen, Li Xu, Man Li, Binyao Tian, Li Yao, Xinwang Zhu","doi":"10.1111/jcmm.70090","DOIUrl":"https://doi.org/10.1111/jcmm.70090","url":null,"abstract":"Mitochondrial dysfunction is a pivotal event contributing to the development of ageing-related kidney disorders. Lon protease 1 (LONP1) has been reported to be responsible for ageing-related renal fibrosis; however, the underlying mechanism(s) of LONP1-driven kidney ageing with respect to mitochondrial disturbances remains to be further explored. The level of LONP1 was tested in the kidneys of aged humans and mice. Renal fibrosis and mitochondrial quality control were confirmed in the kidneys of aged mice. Effects of LONP1 silencing or overexpression on renal fibrosis and mitochondrial quality control were explored. In addition, N6-methyladenosine (m6A) modification and methyltransferase like 3 (METTL3) levels, the relationship between LONP1 and METTL3, and the impacts of METTL3 overexpression on mitochondrial functions were confirmed. Furthermore, the expression of insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) and the regulatory effects of IGF2BP2 on LONP1 were confirmed in vitro. LONP1 expression was reduced in the kidneys of aged humans and mice, accompanied by renal fibrosis and mitochondrial dysregulation. Overexpression of LONP1 alleviated renal fibrosis and maintained mitochondrial homeostasis, while silencing of LONP1 had the opposite effect. Impaired METTL3-m6A signalling contributed at least in part to ageing-induced LONP1 modification, reducing subsequent degradation in an IGF2BP2-dependent manner. Moreover, METTL3 overexpression alleviated proximal tubule cell injury, preserved mitochondrial stability, inhibited LONP1 degradation, and protected mitochondrial functions. LONP1 mediates mitochondrial function in kidney ageing and that targeting LONP1 may be a potential therapeutic strategy for improving ageing-related renal fibrosis.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Brain organoids: A new tool for modelling of neurodevelopmental disorders 脑器质性组织：神经发育障碍建模的新工具

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-09-11 DOI: 10.1111/jcmm.18560

Yirizhati Aili, Nuersimanguli Maimaitiming, Zengliang Wang, Yongxin Wang

{"title":"Brain organoids: A new tool for modelling of neurodevelopmental disorders","authors":"Yirizhati Aili, Nuersimanguli Maimaitiming, Zengliang Wang, Yongxin Wang","doi":"10.1111/jcmm.18560","DOIUrl":"https://doi.org/10.1111/jcmm.18560","url":null,"abstract":"Neurodevelopmental disorders are mostly studied using mice as models. However, the mouse brain lacks similar cell types and structures as those of the human brain. In recent years, emergence of three-dimensional brain organoids derived from human embryonic stem cells or induced pluripotent stem cells allows for controlled monitoring and evaluation of early neurodevelopmental processes and has opened a window for studying various aspects of human brain development. However, such organoids lack original anatomical structure of the brain during maturation, and neurodevelopmental maturation processes that rely on unique cellular interactions and neural network connections are limited. Consequently, organoids are difficult to be used extensively and effectively while modelling later stages of human brain development and disease progression. To address this problem, several methods and technologies have emerged that aim to enhance the sophisticated regulation of brain organoids developmental processes through bioengineering approaches, which may alleviate some of the current limitations. This review discusses recent advances and application areas of human brain organoid culture methods, aiming to generalize optimization strategies for organoid systems, improve the ability to mimic human brain development, and enhance the application value of organoids.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.18560","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Causal association between B cell count and psoriasis using two-sample Mendelian randomization 利用双样本孟德尔随机法研究 B 细胞计数与银屑病之间的因果关系

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-09-11 DOI: 10.1111/jcmm.70089

Zongfeng Zhao, Jie Cheng, Jian Zhu, Sheng Lu, Hongli Lv, Xiujuan Wu

{"title":"Causal association between B cell count and psoriasis using two-sample Mendelian randomization","authors":"Zongfeng Zhao, Jie Cheng, Jian Zhu, Sheng Lu, Hongli Lv, Xiujuan Wu","doi":"10.1111/jcmm.70089","DOIUrl":"https://doi.org/10.1111/jcmm.70089","url":null,"abstract":"To investigate the causality between B cell count and psoriasis by Mendelian randomization (MR). Collected B cell count and psoriasis data from IEU Open GWAS Project. Employed inverse variance weighting (IVW), MR-Egger, WM, weighted mode for analysis, ensuring result robustness. Assessed horizontal pleiotropy with MR-Egger, detected outliers using MR-PRESSO and examined instrumental variables heterogeneity with Cochran's Q-test. The IVW method suggested an association between a genetically predicted memory B cell count and the risk of psoriasis vulgaris. IVW results also showed no causality between other exposure factors and the corresponding outcomes. Also, the global test of MR-PRESSO analysis showed a significant association between a genetically predicted transitional absolute B cell count and the lower risk of psoriasis vulgaris. MR-Egger regression showed that horizontal pleiotropy did not influence the analysis results. We found that memory B cell absolute counts are associated with a lower risk of psoriasis. These data further elucidate the role of memory B cells in psoriasis and provide new options for psoriasis treatment.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hdac3 deficiency limits periosteal reaction associated with Western diet feeding in female mice Hdac3 缺乏症可限制雌性小鼠因摄入西式饮食而产生的骨膜反应

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-09-11 DOI: 10.1111/jcmm.70081

Elizabeth K. Vu, Ismael Y. Karkache, Anthony Pham, Jinsha Koroth, Elizabeth W. Bradley

{"title":"Hdac3 deficiency limits periosteal reaction associated with Western diet feeding in female mice","authors":"Elizabeth K. Vu, Ismael Y. Karkache, Anthony Pham, Jinsha Koroth, Elizabeth W. Bradley","doi":"10.1111/jcmm.70081","DOIUrl":"https://doi.org/10.1111/jcmm.70081","url":null,"abstract":"Diet-induced obesity is associated with enhanced systemic inflammation that limits bone regeneration. HDAC inhibitors are currently being explored as anti-inflammatory agents. Prior reports show that myeloid progenitor-directed Hdac3 ablation enhances intramembranous bone healing in female mice. In this study, we determined if Hdac3 ablation increased intramembranous bone regeneration in mice fed a high-fat/high-sugar (HFD) diet. Micro-CT analyses demonstrated that HFD-feeding enhanced the formation of periosteal reaction tissue of control littermates, reflective of suboptimal bone healing. We confirmed enhanced bone volume within the defect of Hdac3-ablated females and showed that Hdac3 ablation reduced the amount of periosteal reaction tissue following HFD feeding. Osteoblasts cultured in a conditioned medium derived from Hdac3-ablated cells exhibited a four-fold increase in mineralization and enhanced osteogenic gene expression. We found that Hdac3 ablation elevated the secretion of several chemokines, including CCL2. We then confirmed that Hdac3 deficiency increased the expression of Ccl2. Lastly, we show that the proportion of CCL2-positve cells within bone defects was significantly higher in Hdac3-deficient mice and was further enhanced by HFD. Overall, our studies demonstrate that Hdac3 deletion enhances intramembranous bone healing in a setting of diet-induced obesity, possibly through increased production of CCL2 by macrophages within the defect.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A hypothesis on treatment strategy of severe multicentric Castleman disease with continuous renal replacement therapy 持续肾脏替代疗法治疗重度多中心卡斯特曼病的策略假设

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-09-09 DOI: 10.1111/jcmm.70026

Cătălin Constantinescu, David Kegyes, Bogdan Tigu, Vlad Moisoiu, Olga Grăjdieru, Andrea Szekely, Evangelos Terpos, Ciprian Tomuleasa

{"title":"A hypothesis on treatment strategy of severe multicentric Castleman disease with continuous renal replacement therapy","authors":"Cătălin Constantinescu, David Kegyes, Bogdan Tigu, Vlad Moisoiu, Olga Grăjdieru, Andrea Szekely, Evangelos Terpos, Ciprian Tomuleasa","doi":"10.1111/jcmm.70026","DOIUrl":"https://doi.org/10.1111/jcmm.70026","url":null,"abstract":"Castleman disease (CD) is a rare lymphoproliferative disorder, with non-specific clinical manifestations, often delayed diagnosis and treatment, which pose a significant challenge in the present times. Patients diagnosed with this disease have poor prognosis due to the limited treatment options. Multicentric CD occurs at multiple lymph node stations and is associated with a proinflammatory response that leads to the development of the so-called ‘B symptoms’. IL-6 seems to be a key cytokine involved in various manifestations such as lymphadenopathies, hepatosplenomegaly, and polyclonal hypergammaglobulinemia. Its levels correlate with the activity of the disease. Other consequences of MCD include increased fibrinogen levels leading to deep vein thrombosis and thromboembolic disorders, high hepcidin levels causing anaemia, elevated VEGF levels promoting angiogenesis and vascular permeability, which, along with hypoalbuminemia, induce oedema, ascites, pleural and pericardial effusions, and in severe cases, generalized anasarca. In extreme cases multiple organ failure can occur, often resulting in death. We propose the use of continuous renal replacement therapy (CRRT) in managing severe multicentric CD. Our arguments are based on the principles that CRRT is able to remove IL-6 from circulation thus attenuating the cytokine storm, can influence hepcidin levels, and reduction in oedema, and is often used in multiple organ failure to regain homeostasis control. Therefore, it could be used as a therapy or bridge therapy in severe cases. To sustain our hypothesis with evidence, we have gathered several studies from the literature confirming the successful removal of cytokines, especially IL-6 from circulation, which can be used as a starting point.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cathepsin B in cardiovascular disease: Underlying mechanisms and therapeutic strategies 心血管疾病中的胰蛋白酶 B：基本机制和治疗策略。

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-09-09 DOI: 10.1111/jcmm.70064

Zhulan Cai, Shunyao Xu, Chen Liu

{"title":"Cathepsin B in cardiovascular disease: Underlying mechanisms and therapeutic strategies","authors":"Zhulan Cai, Shunyao Xu, Chen Liu","doi":"10.1111/jcmm.70064","DOIUrl":"10.1111/jcmm.70064","url":null,"abstract":"Cathepsin B (CTSB) is a member of the cysteine protease family, primarily responsible for degrading unnecessary organelles and proteins within the acidic milieu of lysosomes to facilitate recycling. Recent research has revealed that CTSB plays a multifaceted role beyond its function as a proteolytic enzyme in lysosomes. Importantly, recent data suggest that CTSB has significant impacts on different cardiac pathological conditions, such as atherosclerosis (AS), myocardial infarction, hypertension, heart failure and cardiomyopathy. Especially in the context of AS, preclinical models and clinical sample imaging data indicate that the cathepsin activity-based probe can reliably image CTSB activity in foam cells and atherosclerotic plaques; concurrently, it allows synchronous diagnostic and therapeutic interventions. However, our knowledge of CTSB in cardiovascular disease is still in the early stage. This paper aims to provide a comprehensive review of the significance of CTSB in cardiovascular physiology and pathology, with the objective of laying a theoretical groundwork for the development of drugs targeting CTSB.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70064","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Involvement of heparanase in the pathogenesis of acute pancreatitis: Implication of novel therapeutic approaches 肝素酶参与急性胰腺炎的发病机制：新型治疗方法的意义。

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-09-09 DOI: 10.1111/jcmm.18512

Dalit B. Hamo-Giladi, Ahmad Fokra, Edmond Sabo, Aviva Kabala, Irena Minkov, Shadi Hamoud, Salim Hadad, Zaid Abassi, Iyad Khamaysi

{"title":"Involvement of heparanase in the pathogenesis of acute pancreatitis: Implication of novel therapeutic approaches","authors":"Dalit B. Hamo-Giladi, Ahmad Fokra, Edmond Sabo, Aviva Kabala, Irena Minkov, Shadi Hamoud, Salim Hadad, Zaid Abassi, Iyad Khamaysi","doi":"10.1111/jcmm.18512","DOIUrl":"10.1111/jcmm.18512","url":null,"abstract":"Acute pancreatitis (AP) is a common gastrointestinal disease with high morbidity and mortality rate. Unfortunately, neither the etiology nor the pathophysiology of AP are fully understood and causal treatment options are not available. Recently we demonstrated that heparanase (Hpa) is adversely involved in the pathogenesis of AP and inhibition of this enzyme ameliorates the manifestation of the disease. Moreover, a pioneer study demonstrated that Aspirin has partial inhibitory effect on Hpa. Another compound, which possesses a mild pancreato-protective effect against AP, is Trehalose, a common disaccharide. We hypothesized that combination of Aspirin, Trehalose, PG545 (Pixatimod) and SST0001 (Roneparstat), specific inhibitors of Hpa, may exert pancreato-protective effect better than each drug alone. Thus, the current study examines the pancreato-protective effects of Aspirin, Trehalose, PG545 and SST0001 in experimental model of AP induced by cerulein in wild-type (WT) and Hpa over-expressing (Hpa-Tg) mice. Cerulein-induced AP in WT mice was associated with significant rises in the serum levels of lipase (X4) and amylase (X3) with enhancement of pancreatic edema index, inflammatory response, and autophagy. Responses to cerulein were all more profound in Hpa-Tg mice versus WT mice, evident by X7 and X5 folds increase in lipase and amylase levels, respectively. Treatment with Aspirin or Trehalose alone and even more so in combination with PG545 or SST0001 were highly effective, restoring the serum level of lipase back to the basal level. Importantly, a novel newly synthesized compound termed Aspirlose effectively ameliorated the pathogenesis of AP as a single agent. Collectively, the results strongly indicate that targeting Hpa by using anti-Hpa drug combinations constitute a novel therapy for this common orphan disease.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.18512","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multifaceted bioinformatic analysis of m6A-related ferroptosis and its link with gene signatures and tumour-infiltrating immune cells in gliomas 对与 m6A 相关的铁凋亡及其与胶质瘤中基因特征和肿瘤浸润免疫细胞的联系的多方面生物信息学分析。

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-09-09 DOI: 10.1111/jcmm.70060

Yang Yang, Liu Hao, Liu Guiyang, Piao Haozhe

{"title":"Multifaceted bioinformatic analysis of m6A-related ferroptosis and its link with gene signatures and tumour-infiltrating immune cells in gliomas","authors":"Yang Yang, Liu Hao, Liu Guiyang, Piao Haozhe","doi":"10.1111/jcmm.70060","DOIUrl":"10.1111/jcmm.70060","url":null,"abstract":"Whether N6-Methyladenosine (m6A)- and ferroptosis-related genes act on immune responses to regulate glioma progression remains unanswered. Data of glioma and corresponding normal brain tissues were fetched from the TCGA database and GTEx. Differentially expressed genes (DEGs) were identified for GO and KEGG enrichment analyses. The FerrDb database was based to yield ferroptosis-related DEGs. Hub genes were then screened out using the cytoHubba database and validated in clinical samples. Immune cells infiltrating into the glioma tissues were analysed using the CIBERSORT R script. The association of gene signature underlying the m6A-related ferroptosis with tumour-infiltrating immune cells and immune checkpoints in low-grade gliomas was analysed. Of 6298 DEGs enriched in mRNA modifications, 144 were ferroptosis-related; NFE2L2 and METTL16 showed the strongest positive correlation. METTL16 knockdown inhibited the migrative and invasive abilities of glioma cells and induced ferroptosis in vitro. NFE2L2 was enriched in the anti-m6A antibody. Moreover, METTL16 knockdown reduced the mRNA stability and level of NFE2L2 (both p < 0.05). Proportions of CD8+ T lymphocytes, activated mast cells and M2 macrophages differed between low-grade gliomas and normal tissues. METTL16 expression was negatively correlated with CD8+ T lymphocytes, while that of NFE2L2 was positively correlated with M2 macrophages and immune checkpoints in low-grade gliomas. Gene signatures involved in the m6A-related ferroptosis in gliomas were identified via bioinformatic analyses. NFE2L2 interacted with METTL16 to regulate the immune response in low-grade gliomas, and both molecules may be novel therapeutic targets for gliomas.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Linoleyl acetate and mandenol alleviate HUA-induced ED via NLRP3 inflammasome and JAK2/STAT3 signalling conduction in rats 乙酸亚油酸酯和曼地诺通过NLRP3炎性体和JAK2/STAT3信号传导缓解HUA诱导的大鼠ED。

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-09-08 DOI: 10.1111/jcmm.70075

Pingyu Ge, Hong Xie, Yinxue Guo, Hang Jin, Lan Chen, Zhichao Chen, Yan Liu

{"title":"Linoleyl acetate and mandenol alleviate HUA-induced ED via NLRP3 inflammasome and JAK2/STAT3 signalling conduction in rats","authors":"Pingyu Ge, Hong Xie, Yinxue Guo, Hang Jin, Lan Chen, Zhichao Chen, Yan Liu","doi":"10.1111/jcmm.70075","DOIUrl":"10.1111/jcmm.70075","url":null,"abstract":"Hyperuricemia (HUA) is characterized by elevated blood uric acid levels, which can increase the risk of erectile dysfunction (ED). Clinical studies have demonstrated satisfactory efficacy of a traditional Chinese medicine formula QYHT decoction in improving ED. Furthermore, the main monomeric components of this formula, linoleyl acetate and mandenol, demonstrate promise in the treatment of ED. This study established an ED rat model induced by HUA and the animals were administered with linoleyl acetate and mandenol. HE and TUNEL were performed to detect tissue changes, ELISA to measure the levels of serum testosterone (T), MDA, NO, CRP, and TNF-α and qPCR and WB to assess the expression levels of NLRP3, ASC, Caspase-1, JAK2, and STAT3 in whole blood. The findings showed that linoleyl acetate and mandenol improved kidney tissue morphology, reduced cell apoptosis in penile tissue, significantly increased T and NO levels, while substantially decreasing levels of MDA, CRP, and TNF-α. Meanwhile, the expression of NLRP3, ASC, and Caspase-1 mRNAs and proteins was markedly reduced, and the phosphorylation of JAK2 and STAT3 was inhibited. These findings were further validated through faecal microbiota transplantation results. Taken together, linoleyl acetate and mandenol could inhibit NLRP3 inflammasome activation, reduce inflammatory and oxidative stress responses, suppress the activity of JAK–STAT signalling pathway, ultimately providing a potential treatment for HUA-induced ED.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A common variant in PIK3CG gene associated with the prognosis of heart failure 与心力衰竭预后相关的 PIK3CG 基因常见变异。

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-09-08 DOI: 10.1111/jcmm.70069

Dong Hu, Lei Xiao, Shiyang Li

{"title":"A common variant in PIK3CG gene associated with the prognosis of heart failure","authors":"Dong Hu, Lei Xiao, Shiyang Li","doi":"10.1111/jcmm.70069","DOIUrl":"10.1111/jcmm.70069","url":null,"abstract":"Phosphoinositide 3-kinase γ (PI3Kγ) is G-protein-coupled receptor-activated lipid kinase with both kinase-dependent and kinase-independent activity. Plenty of evidence have demonstrated that PI3Kγ participated in TAC and I/R-induced myocardial remodelling and heart failure (HF). In this study, we tested the hypothesis that common variants in the PI3Kγ gene (PIK3CG) were associated with the prognosis of HF in the Chinese Han population. Through re-sequencing and genotyping, we finally identified a common variant in the 3′UTR of PIK3CG strongly associated with the prognosis of HF in two-stage population: adjusted p = 0.007, hazard ratio = 0.56 (0.36–0.85) in the first cohort and adjusted p = 0.024, hazard ratio = 0.39 (0.17–0.88) in the replicated cohort. A series of functional assays revealed that rs10215499-A allele suppressed PIK3CG translation by facilitating has-miR-133a-3p binding, but not the G allele. Subjects carrying the GG genotype showed higher mRNA and protein level than those with AA and AG genotype. Furthermore, overexpression of PIK3CG could protect AC16 from hypoxia/reoxygenation (H/R)-induced apoptosis, while the case was opposite for PIK3CG silencing. In conclusion, common variant rs10215499 in the 3′-UTR of PIK3CG might affect the prognosis of HF by interfering with miR-133a-3p binding and PIK3CG is a promising target for HF treatment in the future.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0