Life sciences最新文献_第6页

Recent pharmacological insights on abating toxic protein species burden in neurological disorders: Emphasis on 26S proteasome activation 关于减轻神经系统疾病中有毒蛋白质负担的最新药理学见解：重点关注 26S 蛋白酶体的激活。

IF 5.2 2区医学

Life sciences Pub Date : 2024-11-01 DOI: 10.1016/j.lfs.2024.123206

Mahmoud A. Desouky, Haidy E. Michel, Doaa A. Elsherbiny, Mina Y. George

{"title":"Recent pharmacological insights on abating toxic protein species burden in neurological disorders: Emphasis on 26S proteasome activation","authors":"Mahmoud A. Desouky, Haidy E. Michel, Doaa A. Elsherbiny, Mina Y. George","doi":"10.1016/j.lfs.2024.123206","DOIUrl":"10.1016/j.lfs.2024.123206","url":null,"abstract":"<div><div>Protein homeostasis (proteostasis) refers to the plethora of mechanisms that safeguard the proper folding of the newly synthesized proteins. It entails various intricately regulated cues that demolish the toxic protein species to prevent their aggregation. The ubiquitin-proteasome system (UPS) is recognized as a salient protein degradation system, with a substantial role in maintaining proteostasis. However, under certain circumstances the protein degradation capacity of the UPS is overwhelmed, leading to the accumulation of misfolded proteins. Several neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Huntington disease, and amyotrophic lateral sclerosis are characterized with the presence of protein aggregates and proteinopathy. Accordingly, enhancing the 26S proteasome degradation activity might delineate a pioneering approach in targeting various proteotoxic disorders. Regrettably, the exact molecular approaches that enhance the proteasomal activity are still not fully understood. Therefore, this review aimed to underscore several signaling cascades that might restore the degradation capacity of this molecular machine. In this review, we discuss the different molecular components of the UPS and how 26S proteasomes are deleteriously affected in many neurodegenerative diseases. Moreover, we summarize different signaling pathways that can be utilized to renovate the 26S proteasome functional capacity, alongside currently known druggable targets in this circuit and various classes of proteasome activators.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123206"},"PeriodicalIF":5.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the molecular underpinnings of macrosomia in gestational diabetes mellitus: The role of EGFR signaling and placental syncytiotrophoblast 探索妊娠期糖尿病大畸形的分子基础：表皮生长因子受体信号转导和胎盘合体滋养细胞的作用。

IF 5.2 2区医学

Life sciences Pub Date : 2024-11-01 DOI: 10.1016/j.lfs.2024.123207

Peng Xu , Zewen Sun , Shu Zheng , Lin Pan , Shuai Dong , Jin He , Peng Chen , Chang Shu

{"title":"Exploring the molecular underpinnings of macrosomia in gestational diabetes mellitus: The role of EGFR signaling and placental syncytiotrophoblast","authors":"Peng Xu , Zewen Sun , Shu Zheng , Lin Pan , Shuai Dong , Jin He , Peng Chen , Chang Shu","doi":"10.1016/j.lfs.2024.123207","DOIUrl":"10.1016/j.lfs.2024.123207","url":null,"abstract":"<div><div>Macrosomia, which is frequently associated with gestational diabetes mellitus (GDM), is linked to maternal glycemic control during gestation. When GDM is complicated by macrosomia (GDMM), the placenta exhibits increased mass, underscoring its role as a critical nexus for maternal-fetal nutrient exchange. Despite this recognized correlation, the underlying mechanisms propelling placental hypertrophy have remained elusive. Our study leveraged single-cell RNA transcriptome sequencing of GDMM placental tissues to pinpoint the specific syncytiotrophoblast (SCT) subsets that regulate placental dimensions. Notably, we observed pronounced upregulation of the epidermal growth factor receptor (EGFR) and its corresponding ligands, with a particular emphasis on the autoregulatory cascade involving the glycoprotein hormone alpha subunit (CGA), EGFR, and the transcription factor GATA binding protein 2 (GATA2), as well as perturbations in hormonal homeostasis within the SCT. Furthermore, our cell interaction analysis revealed an enhanced interplay between myeloid cells and SCT3, augmenting the EGFR signaling pathway. These molecular exchanges underscore the pivotal role of the placental immune microenvironment in the etiology of macrosomia, shedding light on the pathophysiology of GDMM and paving the way for novel therapeutic approaches.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123207"},"PeriodicalIF":5.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

AMP kinase: A promising therapeutic drug target for post-COVID-19 complications AMP 激酶：有希望成为治疗 COVID-19 后并发症的药物靶点。

IF 5.2 2区医学

Life sciences Pub Date : 2024-11-01 DOI: 10.1016/j.lfs.2024.123202

Mohammad Saquib Ashraf , Kanika Tuli , Shadman Moiz , Satish Kumar Sharma , Deepa Sharma , Mohd Adnan

{"title":"AMP kinase: A promising therapeutic drug target for post-COVID-19 complications","authors":"Mohammad Saquib Ashraf , Kanika Tuli , Shadman Moiz , Satish Kumar Sharma , Deepa Sharma , Mohd Adnan","doi":"10.1016/j.lfs.2024.123202","DOIUrl":"10.1016/j.lfs.2024.123202","url":null,"abstract":"<div><div>The COVID-19 pandemic, caused by SARS-CoV-2, has resulted in severe respiratory issues and persistent complications, particularly affecting glucose metabolism. Patients with or without pre-existing diabetes often experience worsened symptoms, highlighting the need for innovative therapeutic approaches. AMPK, a crucial regulator of cellular energy balance, plays a pivotal role in glucose metabolism, insulin sensitivity, and inflammatory responses. AMPK activation, through allosteric or kinase-dependent mechanisms, impacts cellular processes like glucose uptake, fatty acid oxidation, and autophagy. The tissue-specific distribution of AMPK emphasizes its role in maintaining metabolic homeostasis throughout the body. Intriguingly, SARS-CoV-2 infection inhibits AMPK, contributing to metabolic dysregulation and post-COVID-19 complications. AMPK activators like capsaicinoids, curcumin, phytoestrogens, cilostazol, and momordicosides have demonstrated the potential to regulate AMPK activity. Compounds from various sources improve fatty acid oxidation and insulin sensitivity, with metformin showing opposing effects on AMPK activation compared to the virus, suggesting potential therapeutic options. The diverse effects of AMPK activation extend to its role in countering viral infections, further highlighting its significance in COVID-19. This review explores AMPK activation mechanisms, its role in metabolic disorders, and the potential use of natural compounds to target AMPK for post-COVID-19 complications. Also, it aims to review the possible methods of activating AMPK to prevent post-COVID-19 diabetes and cardiovascular complications. It also explores the use of natural compounds for their therapeutic effects in targeting the AMPK pathways. Targeting AMPK activation emerges as a promising avenue to mitigate the long-term effects of COVID-19, offering hope for improved patient outcomes and a better quality of life.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123202"},"PeriodicalIF":5.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DDIT4 promotes erythroid differentiation and coordinates with SIPA1 to regulate erythroid proliferation in bone marrow of high altitude erythrocytosis DDIT4 可促进红细胞分化，并与 SIPA1 相互配合，调节高海拔红细胞增多症骨髓中红细胞的增殖。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-31 DOI: 10.1016/j.lfs.2024.123212

Yu Cui , Xiao-yin Zhou , Xiao-xu Li , Yi-dong Yang , Cheng-zhong Yang , De-wei Chen , Jian Huang , Yu-qi Gao

{"title":"DDIT4 promotes erythroid differentiation and coordinates with SIPA1 to regulate erythroid proliferation in bone marrow of high altitude erythrocytosis","authors":"Yu Cui , Xiao-yin Zhou , Xiao-xu Li , Yi-dong Yang , Cheng-zhong Yang , De-wei Chen , Jian Huang , Yu-qi Gao","doi":"10.1016/j.lfs.2024.123212","DOIUrl":"10.1016/j.lfs.2024.123212","url":null,"abstract":"<div><div>Erythrocytosis moderately enhances the oxygen-carrying capacity of the blood and is considered a characteristic response of individuals adapting from low-altitude regions to high-altitude regions. Nevertheless, erythrocytosis can also turn excessive and result in maladaptive syndromes, such as high altitude polycythemia (HAPC). The increased differentiation or proliferation of erythroid cells in the bone marrow may be a crucial factor leading to accumulation of peripheral erythroid cells. However, the mechanism of erythroid regulation within the bone marrow of high-altitude erythrocytosis remains insufficiently systematically observed. We utilized single-cell transcription sequencing to characterize bone marrow cells following chronic hypoxic exposure and found that bone marrow erythrocytosis is associated with the accumulation of Baso-E, Poly-E, and Ortho-E cells at the terminal stage of erythroid lineage differentiation. Through analysis of differential gene expression and localization in differentiated cells within the erythroid lineage, we confirmed that DDIT4 expression was localized in advanced differentiated erythroblast including Baso-E, Poly-E and Ortho-E, its expression was significantly enhanced by hypoxia exposure. We demonstrated that overexpression of DDIT4 could promote K562 cell differentiation, and through the IP pull-down interaction protein profile, we found that DDIT4 might participate in regulating the cell cycle by interacting with SIPA1 to promote the proliferation of erythroid cells and may be involved in HAPC.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123212"},"PeriodicalIF":5.2,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GraphCVAE: Uncovering cell heterogeneity and therapeutic target discovery through residual and contrastive learning GraphCVAE：通过残差和对比学习发现细胞异质性和治疗靶点

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-31 DOI: 10.1016/j.lfs.2024.123208

Zhiwei Zhang, Mengqiu Wang, Ruoyan Dai, Zhenghui Wang, Lixin Lei, Xudong Zhao, Kaitai Han, Chaojing Shi, Qianjin Guo

{"title":"GraphCVAE: Uncovering cell heterogeneity and therapeutic target discovery through residual and contrastive learning","authors":"Zhiwei Zhang, Mengqiu Wang, Ruoyan Dai, Zhenghui Wang, Lixin Lei, Xudong Zhao, Kaitai Han, Chaojing Shi, Qianjin Guo","doi":"10.1016/j.lfs.2024.123208","DOIUrl":"10.1016/j.lfs.2024.123208","url":null,"abstract":"<div><div>Advancements in Spatial Transcriptomics (ST) technologies in recent years have transformed the analysis of tissue structure and function within spatial contexts. However, accurately identifying spatial domains remains challenging due to data sparsity and noise. Traditional clustering methods often fail to capture spatial dependencies, while spatial clustering methods struggle with batch effects and data integration. We introduce GraphCVAE, a model designed to enhance spatial domain identification by integrating spatial and morphological information, correcting batch effects, and managing heterogeneous data. GraphCVAE employs a multi-layer Graph Convolutional Network (GCN) and a variational autoencoder to improve the representation and integration of spatial information. Through contrastive learning, the model captures subtle differences between cell types and states. Extensive testing on various ST datasets demonstrates GraphCVAE's robustness and biological contributions. In the dorsolateral prefrontal cortex (DLPFC) dataset, it accurately delineates cortical layer boundaries. In glioblastoma, GraphCVAE reveals critical therapeutic targets such as TF and NFIB. In colorectal cancer, it explores the role of the extracellular matrix in colorectal cancer. The model's performance metrics consistently surpass existing methods, validating its effectiveness. GraphCVAE's advanced visualization capabilities further highlight its precision in resolving spatial structures, making it a powerful tool for spatial transcriptomics analysis and offering new insights into disease studies.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123208"},"PeriodicalIF":5.2,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The distinct mechanism regulating taurine homeostasis in mice: Nutrient availability affects taurine levels in the liver and energy restriction influences it in the intestine 调节小鼠体内牛磺酸平衡的独特机制：营养供应会影响肝脏中的牛磺酸水平，而能量限制则会影响肠道中的牛磺酸水平。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-31 DOI: 10.1016/j.lfs.2024.123213

András Gregor , Arturo Auñon-Lopez , Marc Pignitter , Kalina Duszka

{"title":"The distinct mechanism regulating taurine homeostasis in mice: Nutrient availability affects taurine levels in the liver and energy restriction influences it in the intestine","authors":"András Gregor , Arturo Auñon-Lopez , Marc Pignitter , Kalina Duszka","doi":"10.1016/j.lfs.2024.123213","DOIUrl":"10.1016/j.lfs.2024.123213","url":null,"abstract":"<div><h3>Aims</h3><div>Our previous findings indicate that caloric restriction (CR) stimulates the production and secretion of taurine-conjugated bile acids in mice. Subsequent processing by gut microbiota leads to increased levels of deconjugated bile acids, taurine, and various taurine conjugates in the intestine. Furthermore, we demonstrated that carbohydrate restriction and protein restriction, to a smaller extent, mirror the impact of CR in terms of hepatic production of bile acids but not their secretion. We hypothesized that modulating dietary macronutrient levels would influence taurine homeostasis in the liver and intestine of ad libitum-fed and CR animals.</div></div><div><h3>Materials and methods</h3><div>Ad libitum-fed male mice were allocated to receive either a control, low-protein (LP), low-fat (LF), or low-carbohydrate (LC) diet. Meanwhile, CR groups were given 80 % of their regular voluntary food intake as a control, high-protein (HP), high-fat (HF), or high-carbohydrate (HC) diet.</div></div><div><h3>Key findings</h3><div>While CR did not affect the taurine levels and its conjugates in the liver, alteration in carbohydrates and protein intake impacted it. Conversely, in the intestine, CR increased the amount of free and conjugated taurine, whereas the various diets did not affect it or disrupt the CR-specific phenotype. Notably, variations in diet composition impacted the expression of the taurine transporter (<em>Slc6a6</em>) and glutathione-S transferases (GST) in the intestine as well as cysteine dioxygenase (<em>Cdo</em>) in the liver.</div></div><div><h3>Significance</h3><div>The liver and the intestine show distinct responses to dietary interventions, with hepatic taurine being affected by the diet composition, while intestinal taurine is governed by energy availability.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123213"},"PeriodicalIF":5.2,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nanomedicine in cardiology: Precision drug delivery for enhanced patient outcomes 心脏病学中的纳米医学：精准给药，提高患者疗效。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-31 DOI: 10.1016/j.lfs.2024.123199

Fengli Peng , Zimu Wang , Zhimei Qiu , Wei Zhang , Yongchao Zhao , Chaofu Li , Bei Shi

{"title":"Nanomedicine in cardiology: Precision drug delivery for enhanced patient outcomes","authors":"Fengli Peng , Zimu Wang , Zhimei Qiu , Wei Zhang , Yongchao Zhao , Chaofu Li , Bei Shi","doi":"10.1016/j.lfs.2024.123199","DOIUrl":"10.1016/j.lfs.2024.123199","url":null,"abstract":"<div><div>Cardiovascular diseases as a primary driver of global morbidity and mortality. Despite the array of therapeutic avenues in clinical practice, predominantly pharmaceutical and surgical interventions, they often fall short of fully addressing the clinical exigencies of cardiovascular patients. In recent years, nanocarriers have shown great potential in the treatment and diagnose of cardiovascular diseases. They can enhance drug targeting and bioavailability while reducing side effects. Additionally, by improving imaging and detection technologies, they enhance early diagnosis and disease monitoring capabilities. These advancements in technology offer new solutions for precision medicine in cardiovascular diseases, advancing treatment efficacy and disease management.</div><div>Crafted from biomaterials, metals, or their amalgamations, these nanocarriers approximate the dimensions of biologically active molecules like proteins and DNA. Cardiovascular nanomedicine, in its infancy, has only recently burgeoned. Yet, with continual refinement in nanocarrier architecture, drug delivery mechanisms, and therapeutic outcomes, the potential of nanomedical technologies in clinical contexts becomes increasingly evident. This review aims to consolidate the strides made in nanocarrier research concerning the treatment and diagnose of cardiovascular diseases.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"358 ","pages":"Article 123199"},"PeriodicalIF":5.2,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association between metabolic syndrome and benign prostatic hyperplasia: The underlying molecular connection 代谢综合征与良性前列腺增生之间的关系：潜在的分子联系。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-31 DOI: 10.1016/j.lfs.2024.123192

Xun Fu , Yutao Wang , Yi Lu, Jiang Liu, Hongjun Li

{"title":"Association between metabolic syndrome and benign prostatic hyperplasia: The underlying molecular connection","authors":"Xun Fu , Yutao Wang , Yi Lu, Jiang Liu, Hongjun Li","doi":"10.1016/j.lfs.2024.123192","DOIUrl":"10.1016/j.lfs.2024.123192","url":null,"abstract":"<div><div>Benign prostatic hyperplasia (BPH), a common cause of lower urinary tract symptoms (LUTS), has been recently regarded as a metabolic disease. Metabolic syndrome (MetS) is a constellation of metabolic disarrangements, including insulin resistance, obesity, hypertension, and dyslipidemia, and it has been established that these components of MetS are important contributing factors exacerbating the degree of prostatic enlargement and bladder outlet obstruction among patients with BPH. Clinical and experimental studies demonstrated that many molecules, such as insulin, insulin-like growth factor 1 (IGF-1), androgen and estrogen, and adipokines, are involved in the overlapping pathogenesis of BPH and MetS, indicating that clinicians might be able to simultaneously alleviate or cure two diseases by choosing appropriate medications. This article aims to systematically review the pathophysiological aspect and traditional etiology and pathogenesis of BPH and discuss the intricate association between MetS and BPH from the molecular point of view, in an attempt to provide stronger evidence for better treatment of two diseases.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"358 ","pages":"Article 123192"},"PeriodicalIF":5.2,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Activation of the apelin/APJ system by vitamin D attenuates age-related muscle atrophy 维生素 D 激活 apelin/APJ 系统可减轻与年龄有关的肌肉萎缩。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-31 DOI: 10.1016/j.lfs.2024.123205

Yoo Jeong Lee, Gyu Hee Kim, Da Som Lee, Hyeon-Ju Jeong, Joo Hyun Lim

{"title":"Activation of the apelin/APJ system by vitamin D attenuates age-related muscle atrophy","authors":"Yoo Jeong Lee, Gyu Hee Kim, Da Som Lee, Hyeon-Ju Jeong, Joo Hyun Lim","doi":"10.1016/j.lfs.2024.123205","DOIUrl":"10.1016/j.lfs.2024.123205","url":null,"abstract":"<div><h3>Aims</h3><div>Age-related frailty and reduced physical activity contribute to a degenerative loss of muscle mass, function, and strength, which is known as sarcopenia. Increasing evidence has shown that vitamin D has beneficial effects on the muscle health. However, the molecular mechanisms of vitamin D have not been fully elucidated. In this study, we aimed to demonstrate whether vitamin D can overcome muscle atrophy due to aging, especially with respect to the regulation of myokines.</div></div><div><h3>Main methods</h3><div>Young (3-month-old) and aged (18-month-old) C57BL/6 mice were assigned to the following 3 groups: normal diet (1000 IU/kg), vitamin D<sub>3</sub>-supplemented diet (20,000 IU/kg), and normal diet plus exercise for 4 months.</div></div><div><h3>Key findings</h3><div>We found that the reduction in muscle strength and mass due to aging was reversed by vitamin D<sub>3</sub> supplementation. The levels of markers involved in muscle atrophy and cellular senescence in the muscle of the aged mice were substantially decreased by vitamin D<sub>3</sub>. Interestingly, we observed that the expression of apelin and its receptor (APJ), which is known to be secreted after exercise, significantly increased in aged muscles with a vitamin D<sub>3</sub>-supplemented diet but not in the young mice. Moreover, circulating interleukin-6 (IL-6) and growth differentiation factor 8 (GDF8) levels were significantly increased in the aged mice but were restored by vitamin D<sub>3</sub> treatment.</div></div><div><h3>Significance</h3><div>Our present data indicate that vitamin D<sub>3</sub> supplementation ameliorates aging-induced muscle atrophy and senescence, similar to the effects of exercise, suggesting the positive impact of vitamin D as an intervention strategy to prevent aging-induced metabolic diseases.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123205"},"PeriodicalIF":5.2,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gut microbiota as a modulator of type 1 diabetes: A molecular perspective 肠道微生物群是 1 型糖尿病的调节因子：分子视角

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-31 DOI: 10.1016/j.lfs.2024.123187

Lukic Nikola, Lukic Iva

{"title":"Gut microbiota as a modulator of type 1 diabetes: A molecular perspective","authors":"Lukic Nikola, Lukic Iva","doi":"10.1016/j.lfs.2024.123187","DOIUrl":"10.1016/j.lfs.2024.123187","url":null,"abstract":"<div><div>Type 1 diabetes (T1D) is defined as an autoimmune metabolic disorder, characterized by destruction of pancreatic β-cells and high blood sugar levels. If left untreated, T1D results in severe health complications, including cardiovascular and kidney disease, as well as nerve damage, with ultimately grave consequences. Besides the role of genetic and certain environmental factors in T1D development, in the last decade, one new player emerged to affect T1D pathology as well, and that is a gut microbiota. Dysbiosis of gut bacteria can contribute to T1D by gut barrier disruption and the activation of autoimmune response, leading to the destruction of insulin producing cells, causing the development and aggravation of T1D symptoms. The relationship between gut microbiota and diabetes is complex and varies between individuals and additional research is needed to fully understand the effects of gut microbiome alternations in T1D pathogenesis. Therefore, the goal of this review is to understand the current knowledge in underlying molecular mechanism of gut microbiota effects, which leads to the new approaches for further studies in the prevention and treatment of T1D.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123187"},"PeriodicalIF":5.2,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0