Life sciences最新文献

{"title":"Epigenetics as a strategic intervention for early diagnosis and combatting glycolyis-induced chemoresistance in gynecologic cancers","authors":"Sachin G. Nair ,&nbsp;Sonu Benny ,&nbsp;Wesley M. Jose ,&nbsp;T.P. Aneesh","doi":"10.1016/j.lfs.2024.123167","DOIUrl":"10.1016/j.lfs.2024.123167","url":null,"abstract":"<div><div>Prospective prediction from the Australian Institute of Health and Welfare (AIHW) showed a likely incidence of 1 in 23 women diagnosed with gynaecological malignancy, where the incidence of relapse with a drug-resistant clone poses a significant challenge in dealing with it even after initial treatment. Glucose metabolism has been exploited as a therapeutic target under anti-metabolomic study, but the non-specificity narrowed its applicability in cancer. Novel updates over epigenetics as a target in gynaecological cancer offer a rational idea of using this in the metabolic rewiring in mutated glycolytic flux-induced drug resistance. This review focuses on the application of epigenetic intervention at a diagnostic and therapeutic level to shift the current treatment paradigm of gynaecological cancers from reactive medicine to predictive, preventive, and personalised medicine. It presents the likely epigenetic targets that can be exploited potentially to prevent the therapeutic failure associated with glucose metabolism-induced chemotherapeutic drug resistance.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"358 ","pages":"Article 123167"},"PeriodicalIF":5.2,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503186","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 5-HT-related gut-brain axis in obesity","authors":"Chaoyong Jiang ,&nbsp;Qiong Zhan ,&nbsp;Chang Zeng","doi":"10.1016/j.lfs.2024.123171","DOIUrl":"10.1016/j.lfs.2024.123171","url":null,"abstract":"<div><h3>Aims</h3><div>The incidence of obesity increases annually. It is closely related to the occurrence of cardiovascular diseases, malignant tumors, etc., and has become a major global health problem. 5-hydroxytryptamine (5-HT), a multifunctional monoamine neurotransmitter, is dispersed throughout the central nervous system and digestive tract. It is intimately related to the mechanism of obesity.</div></div><div><h3>Materials and methods</h3><div>PubMed, Web of Science and Embase were carefully searched. We collected articles that are closely related to 5-HT, the gut-brain axis, and obesity.</div></div><div><h3>Key fingdings</h3><div>The gut microbiota not only influences nutrient metabolism but also centrally meditates appetite and mood regulation. The gut-brain axis, a system connecting the gut and the brain, is known to participate in two-way communication between the gut flora and the central nervous system.</div></div><div><h3>Significance</h3><div>There have been few reports on whether peripheral and central 5-HT interact bidirectionally via the gut-brain axis and jointly play a role in the pathogenesis of obesity. In this review, we summarize the rationale for the contribution of the 5-HT-related gut-brain axis to the development of obesity and explore feasible signaling pathways, which elucidates new targets for preventing and treating obesity.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"358 ","pages":"Article 123171"},"PeriodicalIF":5.2,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503182","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":"A novel exosome-like nanovesicles from Cordyceps militaris potentiate immunomodulatory and anti-tumor effect by reprogramming macrophages","authors":"Yuanyuan Luo ,&nbsp;Xiaozheng Ou ,&nbsp;De Liu ,&nbsp;Hui Shi ,&nbsp;Jiapei Liao ,&nbsp;Rongmin Yu ,&nbsp;Liyan Song ,&nbsp;Jianhua Zhu","doi":"10.1016/j.lfs.2024.123163","DOIUrl":"10.1016/j.lfs.2024.123163","url":null,"abstract":"<div><h3>Aims</h3><div>Fungi-derived exosome-like nanovesicles (ENs) are emerging as a highly promising class of nanoparticles, particularly noted for their cost-effective production. However, their impact on immune regulation and their potential as anti-tumor agents need further exploration. Our study specifically focused on the investigation of the immunomodulatory and anti-tumor properties of ENs derived from <em>Cordyceps militaris</em>, an edible fungus that had achieved large-scale commercial production, referred to as CMDENs.</div></div><div><h3>Main methods</h3><div>The ENs of <em>C. militaris</em> were collected through ultra-high-speed centrifugation, followed by characterization of their physicochemical properties and contents. Subsequently, the biological distribution of these vesicles was investigated using <em>in vivo</em> fluorescence imaging experiments. Finally, the immune activation and polarization of macrophages were examined through both <em>in vitro</em> and <em>in vivo</em> experiments.</div></div><div><h3>Key findings</h3><div>Herein, we presented the discovery of CMDENs that were rich in proteins, lipids, flavonoids and alkaloids. Immunomodulatory experiments conducted <em>in vivo</em> demonstrated that CMDENs exhibited protective effects against cyclophosphamide-induced immunosuppression in mice by significantly enhancing macrophage phagocytosis and peripheral blood immune cell counts. Moreover, CMDENs effectively induced the polarization of M0- and M2-like macrophages toward M1-like phenotype by activating MAPKs signaling pathway. Notably, CMDENs exhibited remarkable capabilities in inhibiting tumor growth by reprogramming tumor-associated macrophages and activating tumor-infiltrating T lymphocytes, without any observed toxicity in mice bearing tumors.</div></div><div><h3>Significance</h3><div>Our research suggested that CMDENs possessed the potential to be explored as a nano-immunomodulatory agent for cancer.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"358 ","pages":"Article 123163"},"PeriodicalIF":5.2,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503183","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":"Rodent models in sensorineural hearing loss research: A comprehensive review","authors":"Wenjing Li ,&nbsp;Baoying Xu ,&nbsp;Yuqi Huang ,&nbsp;Xueling Wang ,&nbsp;Dehong Yu","doi":"10.1016/j.lfs.2024.123156","DOIUrl":"10.1016/j.lfs.2024.123156","url":null,"abstract":"<div><div>Sensorineural hearing loss (SNHL) constitutes a major global health challenge, affecting millions of individuals and substantially impairing social integration and quality of life. The complexity of the auditory system and the multifaceted nature of SNHL necessitate advanced methodologies to understand its etiology, progression, and potential therapeutic interventions. This review provides a comprehensive overview of the current animal models used in SNHL research, focusing on their selection based on specific characteristics and their contributions to elucidating pathophysiological mechanisms and evaluating novel treatment strategies. It discusses the most commonly used rodent models in hearing research, including mice, rats, guinea pigs, Mongolian gerbils, and chinchillas. Through a comparative analysis, this review underscores the importance of selecting models that align with specific research objectives in SNHL studies, discussing the advantages and limitations of each model. By advocating for a multidisciplinary approach that leverages the strengths of various animal models with technological advancements, this review aims to facilitate significant advancements in the prevention, diagnosis, and treatment of sensorineural hearing loss.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"358 ","pages":"Article 123156"},"PeriodicalIF":5.2,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503180","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":"ACE and ACE2 activities and polymorphisms assessment: A populational study from Ipaussu (SP, Brazil) during the COVID-19 pandemic","authors":"Lilian dos Santos ,&nbsp;Lys Angela Favaroni Mendes Salgado Ribeiro ,&nbsp;Andréia Cristina Febba Gomes ,&nbsp;Nayara Azinheira Nobrega Cruz ,&nbsp;Lilian Caroline Gonçalves de Oliveira,&nbsp;Marcos Antonio Cenedeze,&nbsp;Hélio Tedesco Silva Junior,&nbsp;José Osmar Medina Pestana,&nbsp;Dulce Elena Casarini","doi":"10.1016/j.lfs.2024.123157","DOIUrl":"10.1016/j.lfs.2024.123157","url":null,"abstract":"<div><h3>Aim</h3><div>The angiotensin-converting enzyme 2 (ACE2) and its homolog, the angiotensin converting enzyme 1 (ACE), are involved in COVID-19 physiopathology. Alterations in the enzymatic structure, expression, and/or activity may influence the risk of infection and severity of disease. For this reason, we aimed to identify different allelic forms of <em>ACE2</em> G8790A and <em>ACE</em> I/D polymorphisms in a Brazilian cohort and evaluate their impact on ACE and ACE2 activities and their association with COVID-19 susceptibility and severity.</div></div><div><h3>Main methods</h3><div>A total of 549 COVID-19-negative and 270 COVID-19-positive participants from Ipaussu, Sao Paulo, Brazil, were recruited. ACE2 and ACE activities were measured by fluorogenic assays using MCA-Ala-Pro-Lys(Dnp) as the substrate for ACE2 and <em>Z</em>-Phe-His-Leu-OH (Z-FHL) and Hippuryl-His-Leu-OH (<em>h</em>−HL) as substrates for ACE. Genomic DNA was extracted from EDTA-peripheral blood, and the regions of the genes containing <em>ACE2</em> G8790A and <em>ACE</em> I/D polymorphisms were amplified by PCR-restriction fragment length polymorphism and real-time PCR, respectively.</div></div><div><h3>Key findings</h3><div>The G allele of <em>ACE2</em> G8790A polymorphism and D allele of <em>ACE</em> I/D polymorphism are associated with increased ACE and ACE2 activities. ACE activity ratio (<em>Z</em>-FHL/h-HL), an inflammatory marker, is increased in women with GG genotype and COVID-19-positive diagnosis.</div></div><div><h3>Significance</h3><div>For the first time, it was demonstrated that in females, the GG genotype is associated with increased ACE activity ratio (<em>Z</em>-FHL/h-HL) in the COVID-19-positive group. Elevated ACE activity ratio (Z-FHL/h-HL) is highly linked to inflammation and may justify the associations between the G genotype and COVID-19 severity of symptoms and outcomes.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"358 ","pages":"Article 123157"},"PeriodicalIF":5.2,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503184","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":"Inhibition of proteasome activity facilitates definitive endodermal specification of pluripotent stem cells by influencing YAP signalling","authors":"Akshaya Ashok ,&nbsp;Ashwini Ashwathnarayan ,&nbsp;Smitha Bhaskar ,&nbsp;Spandana Shekar ,&nbsp;Guruprasad Kalathur ,&nbsp;Jyothi Prasanna ,&nbsp;Anujith Kumar","doi":"10.1016/j.lfs.2024.123160","DOIUrl":"10.1016/j.lfs.2024.123160","url":null,"abstract":"<div><h3>Aims</h3><div>The knowledge of the molecular players that regulate the generation of endoderm cells is imperative to obtain homogenous population of pancreatic β-cells from stem cells. The Ubiquitin proteasome system (UPS) has been envisaged as a crucial intracellular protein degradation system, but its role in the generation of β-cells remains elusive. Hence, it would be appropriate to unravel the potential role of UPS in endoderm specification and utilize the understanding to generate β-cells from pluripotent stem cells.</div></div><div><h3>Materials and methods</h3><div>The pluripotent stem cells (mESCs, miPSCs and hIPSCs) were subjected to differentiation towards pancreatic β-cells and assessed the proteasomal activity during endodermal differentiation. Pharmacologic agents MG132 and IU-1 were employed to inhibit and activate proteasomal activity respectively at the definitive endoderm stage to investigate its impact on the generation of β-cells. The expression of stage-specific genes were analyzed at transcript and protein levels. We also explored the role of unfolded protein response and UPS-regulated signalling pathways in endodermal differentiation.</div></div><div><h3>Key findings</h3><div>We observed decreased proteasomal activity specifically during endoderm, but not during the generation of other lineages. Extraneous proteasomal inhibition enhanced the expression of endodermal genes while increasing the proteasomal activity hindered definitive endodermal differentiation. Proteasomal inhibition at the definitive endodermal stage culminated in an enriched generation of insulin-positive cells. Elevated endodermal gene expression was consistent in mESCs and hIPSCs upon proteasomal inhibition. Mechanistic insight revealed the proteasome-inhibited enhanced endodermal differentiation to be via modulating the YAP pathway.</div></div><div><h3>Significance</h3><div>Our study unravels the specific involvement of UPS in endoderm cell generation from pluripotent stem cells and paves the way for obtaining potential definitive endodermal cells for plausible cellular therapy in the future.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"358 ","pages":"Article 123160"},"PeriodicalIF":5.2,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469111","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":"Functionalized metal oxide nanoparticles: A promising intervention against major health burden of diseases","authors":"Kornwalai Tunkaew ,&nbsp;Chaikarn Liewhiran ,&nbsp;Chutima S. Vaddhanaphuti","doi":"10.1016/j.lfs.2024.123154","DOIUrl":"10.1016/j.lfs.2024.123154","url":null,"abstract":"<div><div>Metal oxide nanoparticles (MONPs) is one of the most effective materials for medical applications with their substantial surface metallic ions and high surface area–volume ratio. Over decades, MONPs have been considered potential treatments due to their demonstrated ability and reactivity to target diverse cellular signaling pathways implicated in antimicrobial effects, as well as in the amelioration of oxidative stress, inflammation, cancer progression, and glucose together with lipid dysregulation. Based on their unique characteristics, MONPs have shown to be biodegradable and biocompatible vehicles for drugs, which have recently been applied in drug delivery as nanocarriers to enhance their delivery capacity for mechanistic membrane transport. However, little is known about the precise cellular responses, molecular mechanisms, and potential use of MONPs in the medical field. This review emphasizes on elaborating the biochemical reactivities of MONPs on molecular and cellular reactions, highlighting the physiological responses, mechanisms of action, certain drawbacks, and remediation of these functionalized materials. The significant goal of this literature is to shed light on the new perspectives of MONPs in pre-clinical application to pursue for clinical research as alternative-personalized medicines to prevent individuals from drastic diseases.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"358 ","pages":"Article 123154"},"PeriodicalIF":5.2,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469110","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":"Circulating CD45RA−Foxp3++ Treg cells serve as a biomarker for predicting minimal clinical manifestations status of myasthenia gravis","authors":"Yaru Lu ,&nbsp;Qian Ma ,&nbsp;Lu Yu ,&nbsp;Xiaoxi Liu ,&nbsp;Pei Chen ,&nbsp;Weibin Liu","doi":"10.1016/j.lfs.2024.123162","DOIUrl":"10.1016/j.lfs.2024.123162","url":null,"abstract":"<div><h3>Aims</h3><div>Regulatory T cells (Tregs) are key mediators of the induction of immune tolerance; however, the mechanisms by which they regulate myasthenia gravis (MG) are not fully understood. This study aimed to explore the characteristics of Tregs and their subpopulations in the peripheral blood of patients with minimal clinical manifestations (MM) of MG and identify biomarkers that predict MM-MG for treatment guidance.</div></div><div><h3>Materials and methods</h3><div>The clinical data of patients with general MG who visited our hospital were retrospectively analyzed. Age- and sex-matched volunteers were selected as healthy controls (HC). Flow cytometry was used to determine the proportion, function, and subpopulations of total Tregs. A correlation analysis was conducted for subpopulation proportions and MG disease severity.</div></div><div><h3>Key findings</h3><div>A total of 27 cases of MM-MG, 40 cases of naїve-MG, and 33 cases of HC were included in this study. The number of total Tregs and the suppressive function of total Tregs were elevated in patients with MM-MG compared to those of patients with naїve-MG. Further analysis revealed that the frequency of CD45RA⁻Foxp3⁺⁺ Tregs (a-Tregs) negatively correlated with quantitative myasthenia gravis (QMG) scores for patients with naїve-MG. In addition, the number of a-Tregs was significantly greater in patients with MM-MG than in patients with naїve-MG, and CD45RA⁻Foxp3⁺ Tregs expressed higher and lower levels of CTLA-4 and CXCR3, respectively.</div></div><div><h3>Significance</h3><div>CD45RA⁻Foxp3⁺⁺ Tregs were significantly more abundant and highly expressed surface inhibitory molecules in patients with MM-MG. This profile may serve as a predictive biomarker for MM-MG.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"358 ","pages":"Article 123162"},"PeriodicalIF":5.2,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469107","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":"Surface engineered nano architectonics: An evolving paradigm for tackling Alzheimer's disease","authors":"Mansi Negi,&nbsp;Etikala Amulya,&nbsp;Vivek Phatale,&nbsp;Noella Abraham,&nbsp;Aachal Hedaoo,&nbsp;Dadi A. Srinivasarao,&nbsp;Saurabh Srivastava","doi":"10.1016/j.lfs.2024.123155","DOIUrl":"10.1016/j.lfs.2024.123155","url":null,"abstract":"<div><div>As per the World Health Organization (WHO) estimation, Alzheimer's disease (AD) will affect 100 million population across the globe by 2050. AD is an incurable neurodegenerative disease that remains a mystery for neurologists owing to its complex pathophysiology. Currently, available therapeutic regimens will only cause symptomatic relief by improving the cognitive and behavioral functions of AD. However, the major pitfalls in managing AD include tight junctions in the endothelial cells of the blood-brain barrier (BBB), diminished neuronal bioavailability, enzymatic degradation and reduced stability of the therapeutic moiety. In an effort to surmount the drawbacks mentioned above, researchers shifted their focus toward nanocarriers (NCs). Nevertheless, non-specific targeting of NCs imparts toxicity to the peripheral organs, thereby reducing the bioavailability of therapeutic moiety at the target site. To unravel this unmet clinical need, scientists came up with the idea of a novel intriguing strategy of surface engineering by targeting ligands. Surface-decorated NCs provide targeted drug delivery, controlled drug release, enhanced penetration and bioavailability. In this state-of-the-art review, we have highlighted in detail various molecular signalling pathways involved in AD pathogenesis. The significance of surface functionalization and its application in AD management have been deliberated. We have elaborated on the regulatory bottlenecks and clinical hurdles faced during lab-to-industrial scale translation along with possible solutions.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"358 ","pages":"Article 123155"},"PeriodicalIF":5.2,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469058","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":"A reliable strategy for establishment of an animal model of diabetic cardiomyopathy: Induction by a high-fat diet combined with single or multiple injections of low-dose streptozotocin","authors":"Weixing Wen ,&nbsp;Yue Cao ,&nbsp;Peng Chen ,&nbsp;Jiahuan Li ,&nbsp;Weiwen Li ,&nbsp;Guolin Huang ,&nbsp;Haoxiao Zheng ,&nbsp;Xiaolin Zhu ,&nbsp;Hao Zhang ,&nbsp;Yangxin Chen ,&nbsp;Xiaohui Huang ,&nbsp;Yunzhao Hu ,&nbsp;Yuli Huang","doi":"10.1016/j.lfs.2024.123161","DOIUrl":"10.1016/j.lfs.2024.123161","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic cardiomyopathy (DCM) is one of the leading causes of death in patients with diabetes mellitus (DM). This study aimed to identify a reliable method for establishing an animal model of DCM for investigation of new targets and treatments.</div></div><div><h3>Methods</h3><div>Eighty-four 4-week-old male Sprague–Dawley rats were randomly allocated to receive a normal diet or a high-fat diet (HFD) in an approximate ratio of 1:3. At 9 weeks of age, rats in the HFD group received streptozotocin (STZ) 30 mg/kg by intraperitoneal injection and rats in the control group received the same volume of buffer solution. The rodent model of DM was deemed to be successfully established when a random blood glucose measurement was &gt;16.7 mmol/L on three consecutive occasions. If necessary, STZ was readministered.</div></div><div><h3>Results</h3><div>Three of the 64 rats in the HFD group died after a second STZ injection. DM was induced in 14, 39, and 8 rats after one, two, and three injections, respectively, with cumulative success rates of 21.9 %, 82.8 %, and 95.3 %. Three months later, the rats with DM showed persistent hyperglycemia and insulin resistance and developed histopathological changes indicating cardiac hypertrophy, myocardial fibrosis, and diastolic dysfunction. The metabolic and cardiac histopathological changes were consistent regardless of whether DM was induced by one, two, or three injections of STZ.</div></div><div><h3>Conclusion</h3><div>An HFD combined with one or more intraperitoneal injections of low-dose STZ is a straightforward and reliable method for inducing DCM in rats. When a single dose of STZ fails to induce DM, repeated injections can be considered.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"358 ","pages":"Article 123161"},"PeriodicalIF":5.2,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469046","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}