Life sciences最新文献

{"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 ,&nbsp;Arturo Auñon-Lopez ,&nbsp;Marc Pignitter ,&nbsp;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}

{"title":"Nanomedicine in cardiology: Precision drug delivery for enhanced patient outcomes","authors":"Fengli Peng ,&nbsp;Zimu Wang ,&nbsp;Zhimei Qiu ,&nbsp;Wei Zhang ,&nbsp;Yongchao Zhao ,&nbsp;Chaofu Li ,&nbsp;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}

{"title":"Association between metabolic syndrome and benign prostatic hyperplasia: The underlying molecular connection","authors":"Xun Fu ,&nbsp;Yutao Wang ,&nbsp;Yi Lu,&nbsp;Jiang Liu,&nbsp;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}

{"title":"Activation of the apelin/APJ system by vitamin D attenuates age-related muscle atrophy","authors":"Yoo Jeong Lee,&nbsp;Gyu Hee Kim,&nbsp;Da Som Lee,&nbsp;Hyeon-Ju Jeong,&nbsp;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 D₃-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 D₃ supplementation. The levels of markers involved in muscle atrophy and cellular senescence in the muscle of the aged mice were substantially decreased by vitamin D₃. 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 D₃-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 D₃ treatment.</div></div><div><h3>Significance</h3><div>Our present data indicate that vitamin D₃ 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}

{"title":"Gut microbiota as a modulator of type 1 diabetes: A molecular perspective","authors":"Lukic Nikola,&nbsp;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}

{"title":"Bay 11-7082 mitigates oxidative stress and mitochondrial dysfunction via NLRP3 inhibition in experimental diabetic neuropathy","authors":"Lokesh Sharan ,&nbsp;Anubroto Pal ,&nbsp;S. Sarath Babu ,&nbsp;Ashutosh Kumar ,&nbsp;Sugato Banerjee","doi":"10.1016/j.lfs.2024.123203","DOIUrl":"10.1016/j.lfs.2024.123203","url":null,"abstract":"<div><h3>Objective</h3><div>Diabetic neuropathy is associated with mitochondrial dysfunction and neuroinflammation. Chronic hyperglycemia triggers inflammatory responses and oxidative stress, causing peripheral neuropathy, whereas mitochondrial dysfunction caused by increased ROS generation and reduced bioenergetics maintains the inflammatory cycle. The purpose of this study is to evaluate the pharmacological efficacy of Bay 11–7082 (B11) against diabetic neuropathy in rats.</div></div><div><h3>Methods</h3><div>B11 was administered at doses of 1 and 3 mg/kg to STZ-induced diabetic animals (55 mg/kg, i.p). Behavioral and functional assessments were conducted to assess neuropathy. Molecular protein expressions were evaluated for B11's efficacy against STZ-induced diabetic neuropathic rats and in SHSY5Y cells exposed to 175 mM of <span>d</span>-glucose.</div></div><div><h3>Results</h3><div>Diabetic rats exhibited deficits in nerve functions, altered nociceptive parameters, and increased expression of NLRP3, ASC, Caspase-1, and NF-κB. Additionally, diabetic animals showed reduced levels of PGC1α/Nrf2/HO-1, with an overexpression of PARP1. Compromised mitochondrial function was evident through increased mitochondrial dynamic marker DRP1 and elevated levels of inflammatory cytokines TNF-α, IL-1β, IL-18, and IL-6. However, B11 administration significantly ameliorated these changes, suggesting that B11's NLRP3 inhibition may be attributed to the activation of the mitochondrial biogenesis pathway via PGC1α/Nrf2/HO-1, along with improved mitochondrial health. In high glucose exposed SHSY5Y cells, B11 treatment attenuated neuroinflammation by inhibiting NLRP3 activation and reducing mitochondrial damage.</div></div><div><h3>Conclusion</h3><div>B11, showed a protective effect against diabetic neuropathy by inhibiting oxidative stress, NLRP3 activation, and improving mitochondrial health in experimental diabetic neuropathy. This study provides new mechanistic insights into the neuroprotective role of Bay 11–7082 against diabetic neuropathy.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123203"},"PeriodicalIF":5.2,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564456","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}

{"title":"Longitudinal evaluation of liver stiffness reveals hepatic cholesterol as the determinant of fibrosis progression in mice","authors":"Na Young Lee ,&nbsp;Ja Hyun Koo","doi":"10.1016/j.lfs.2024.123201","DOIUrl":"10.1016/j.lfs.2024.123201","url":null,"abstract":"<div><h3>Aims</h3><div>The metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately 30 % of the global population. While excessive consumption of dietary fat induces steatosis, it does not develop fibrosis, indicating that additional factors are required as “second hits” for further progression of MASLD. Here, based on shear wave elastography, we compared the longitudinal patterns of fibrogenesis induced by different diets and show the crucial role of cholesterol accumulation in fibrosis progression.</div></div><div><h3>Materials and methods</h3><div>Mice were fed chow, high-fat (HFD), high-fat high-cholesterol (HFHCD), choline-deficient, L-amino acid-defined high-fat (CDAHFD), or 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine diets over 12 weeks.</div></div><div><h3>Key findings</h3><div>Mice fed with HFD gained significant amounts of body weight but did not show an increase in liver stiffness. In contrast, the addition of cholesterol in the same diet robustly induced liver stiffening starting from the first week, which was comparable to the CDAHFD-induced fibrosis model. Longitudinal tracking of liver stiffness revealed a two-step progression of fibrosis after prolonged feeding of HFHCD and CDAHFD, likely due to cellular cholesterol accumulation over a certain threshold after the transition point. Biochemical analyses suggested the critical role of both total and hepatic cholesterol accumulation in liver fibrosis development.</div></div><div><h3>Significance</h3><div>Collectively, our results underscore the significance of cholesterol in liver fibrosis development, also highlighting the benefit of monitoring liver stiffness to understand the pathogenesis of liver fibrosis.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"358 ","pages":"Article 123201"},"PeriodicalIF":5.2,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564482","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}

{"title":"Repurposing Aprepitant: Can it protect against doxorubicin-induced Chemobrain beyond its antiemetic role?","authors":"Asmaa A. Gomaa ,&nbsp;Dalaal M. Abdallah ,&nbsp;Hanan S. El-Abhar ,&nbsp;Bassant M. El-Mokadem","doi":"10.1016/j.lfs.2024.123210","DOIUrl":"10.1016/j.lfs.2024.123210","url":null,"abstract":"<div><div>The substance P (SP) and neurokinin-1 receptor (NK-1R) axis is crucial in numerous pathological processes, including inflammation, stress responses, pain perception, and vomiting. Consequently, aprepitant, an NK-1R blocker, is used as an antiemetic in chemotherapy, including the use of doxorubicin (DOX), but whether aprepitant can also assuage DOX-mediated chemobrain remains to be unveiled. Here, we scrutinized the potential neuroprotective effect and underlying mechanisms of aprepitant using DOX-induced chemobrain model, where rats were allocated into 4 groups (control, aprepitant, DOX, and DOX+ aprepitant). Cognitive deficits were assessed through behavioral tests and hippocampal structural alterations were determined by H&amp;E and toluidine blue staining. Biochemical measurements were performed using ELISA, real-time quantitative PCR, western blotting, and immunohistochemical methods. Aprepitant improved cognitive responses, and hippocampal morphology, enhancing the presence of intact neurons. At the molecular tier, aprepitant significantly reduced hippocampal contents of SP and the inflammatory markers NF-κB and IL-1β. Additionally, it signified its antioxidant and antiapoptotic capacities by downregulating cleaved caspase-3 protein expression and curbing the content of malondialdehyde but boosted those of glutathione and Bcl-2. Aprepitant also downregulated the expression of miR-146a and turned off the endoplasmic reticulum (ER) stress cascade PERK/eIF-2α/ATF-4/CHOP. To recapitulate, aprepitant demonstrates a neuroprotective effect against DOX-mediated chemobrain by alleviating inflammatory, oxidative, and apoptotic responses, partly by reducing SP, ER stress, and miR-146a. These findings not only underscore the potential of aprepitant as a neuroprotective agent but also offer new understanding of the mechanisms behind chemobrain, leading to better therapeutic strategies for cancer patients.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123210"},"PeriodicalIF":5.2,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564476","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}

{"title":"AI-empowered visualization of nucleic acid testing","authors":"Zehua Lu,&nbsp;Xiaogang Wang,&nbsp;Junge Chen","doi":"10.1016/j.lfs.2024.123209","DOIUrl":"10.1016/j.lfs.2024.123209","url":null,"abstract":"<div><h3>Aims</h3><div>The visualization of nucleic acid testing (NAT) results plays a critical role in diagnosing and monitoring infectious and genetic diseases. The review aims to review the current status of AI-based NAT result visualization. It systematically introduces commonly used AI-based methods and techniques for NAT, emphasizing the importance of result visualization for accessible, clear, and rapid interpretation. This highlights the importance of developing a NAT visualization platform that is user-friendly and efficient, setting a clear direction for future advancements in making nucleic acid testing more accessible and effective for everyday applications.</div></div><div><h3>Method</h3><div>This review explores both the commonly used NAT methods and AI-based techniques for NAT result visualization. The focus then shifts to AI-based methodologies, such as color detection and result interpretation through AI algorithms. The article presents the advantages and disadvantages of these techniques, while also comparing the performance of various NAT platforms in different experimental contexts. Furthermore, it explores the role of AI in enhancing the accuracy, speed, and user accessibility of NAT results, highlighting visualization technologies adapted from other fields of experimentation.</div></div><div><h3>Significance</h3><div>This review offers valuable insights for researchers and everyday users, aiming to develop effective visualization platforms for NAT, ultimately enhancing disease diagnosis and monitoring.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123209"},"PeriodicalIF":5.2,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564546","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}

{"title":"The organoid modeling approach to understanding the mechanisms underlying neurodegeneration: A comprehensive review","authors":"Hanieh Jalali ,&nbsp;Sana Rahimian ,&nbsp;Nasim Shahsavarian ,&nbsp;Rozhan Norouzi ,&nbsp;Zahra Ahmadiyeh ,&nbsp;Hossein Najafi ,&nbsp;Hasti Golchin","doi":"10.1016/j.lfs.2024.123198","DOIUrl":"10.1016/j.lfs.2024.123198","url":null,"abstract":"<div><div>Neurodegenerative diseases (NDs) are severe disorders of the nervous system, and their causes are still not completely understood. Modeling the complex pathological mechanisms underlying NDs has long posed a significant challenge, as traditional <em>in vitro</em> and animal models often fail to accurately recapitulate the disease phenotypes observed in humans; however, the rise of organoid technology has opened new approaches for developing innovative disease models that can better capture the nuances of the human nervous system. Organoid platforms hold promise for contributing to the design of future clinical trials and advancing our understanding of these devastating neurological conditions and accelerate the discovery of effective, personalized therapies. This comprehensive review discusses the recent advancements in neural organoid technology and explores the potential of patient-derived organoids for modeling NDs conditions and presents findings related to the mechanisms of their development or progress.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"358 ","pages":"Article 123198"},"PeriodicalIF":5.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564484","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}