Life sciences最新文献_第5页

Genetics, epigenetics and autoimmunity constitute a Bermuda triangle for the pathogenesis of rheumatoid arthritis 遗传学、表观遗传学和自身免疫学构成了类风湿关节炎发病机制的百慕大三角。

IF 5.2 2区医学

Life sciences Pub Date : 2024-09-26 DOI: 10.1016/j.lfs.2024.123075

{"title":"Genetics, epigenetics and autoimmunity constitute a Bermuda triangle for the pathogenesis of rheumatoid arthritis","authors":"","doi":"10.1016/j.lfs.2024.123075","DOIUrl":"10.1016/j.lfs.2024.123075","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA), a multigene disorder with a heritability rate of 60 %, is characterized by persistent pain, synovial hyperplasia, and cartilage and bone destruction, ultimately causing irreversible joint deformity. The etiology and pathogenesis of rheumatoid arthritis (RA) are primarily influenced by specific genetic variants, particularly HLA alleles such as HLA-DRB1*01 and DRB1*04. However, other HLA alleles such as HLA-DRB1*10 and DPB*1 have also been found to contribute to increased susceptibility to RA. However, non-HLA genes also confer a comparatively high risk of RA disease manifestation. The most relevant single nucleotide polymorphisms (SNPs) associated with non-HLA genes are PTPN22, TRAF1, CXCL-12, TBX-5, STAT4, FCGR, PADI4, and MTHFR. In conjunction with genetic susceptibility, epigenetic alterations orchestrate paramount involvement in regulating RA pathogenesis. Increasing evidence implicates DNA methylation and histone protein modifications, including acetylation and methylation, as the primary epigenetic mechanisms that drive the pathogenesis and clinical progression of the disease. In addition to genetic and epigenetic changes, autoimmune inflammation also determines the pathological progression of the synovial membrane in joints with RA. Glycosylation changes, such as sialylation and fucosylation, in immune cells have been shown to be relevant to disease progression. Genetic heterogeneity, epigenetic factors, and changes in glycosylation do not fully explain the features of RA. Therefore, investigating the interplay between genetics, epigenetics, and autoimmunity is crucial. This review highlights the significance and interaction of these elements in RA pathophysiology, suggesting their diagnostic potential and opening new avenues for novel therapeutic approaches.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349487","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

Out-of-phase treatment with the synthetic glucocorticoid betamethasone disturbs glucose metabolism in mice 合成糖皮质激素倍他米松的非阶段性治疗会扰乱小鼠的糖代谢。

IF 5.2 2区医学

Life sciences Pub Date : 2024-09-25 DOI: 10.1016/j.lfs.2024.123080

{"title":"Out-of-phase treatment with the synthetic glucocorticoid betamethasone disturbs glucose metabolism in mice","authors":"","doi":"10.1016/j.lfs.2024.123080","DOIUrl":"10.1016/j.lfs.2024.123080","url":null,"abstract":"<div><h3>Objective</h3><div>Endogenous glucocorticoid levels display a strong circadian rhythm, which is often not considered when synthetic glucocorticoids are prescribed as anti-inflammatory drugs. In this study we evaluated the effect timing of glucocorticoid administration, i.e. in-phase (administered when endogenous glucocorticoid levels are high) versus out-of-phase (administered when endogenous glucocorticoid levels are low). We investigated the synthetic glucocorticoid betamethasone – which is extensively used in the clinic - and monitored the development of common metabolic side effects in mice upon prolonged treatment, with a particular focus on glucose metabolism.</div></div><div><h3>Methods</h3><div>Male and female C57BL/6J mice were treated with the synthetic glucocorticoid betamethasone in-phase and out-of-phase, and the development of metabolic side effects was monitored.</div></div><div><h3>Results</h3><div>We observed that, compared with in-phase treatment, out-of-phase treatment with betamethasone results in hyperinsulinemia in both male and female C57BL/6J mice. We additionally found that out-of-phase betamethasone treatment strongly reduced insulin sensitivity as compared to in-phase administration during morning measurements. Our study shows that the adverse effects of betamethasone are dependent on the time of treatment with generally less side effects on glucose metabolism with in-phase treatment.</div></div><div><h3>Conclusions</h3><div>This study highlights differences in glucocorticoid outcome based on the time of measurement, advocating that potential circadian variation should be taken into account when studying glucocorticoid biology.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349485","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

Phage display screening in breast cancer: From peptide discovery to clinical applications 乳腺癌的噬菌体展示筛选：从多肽发现到临床应用。

IF 5.2 2区医学

Life sciences Pub Date : 2024-09-25 DOI: 10.1016/j.lfs.2024.123077

{"title":"Phage display screening in breast cancer: From peptide discovery to clinical applications","authors":"","doi":"10.1016/j.lfs.2024.123077","DOIUrl":"10.1016/j.lfs.2024.123077","url":null,"abstract":"<div><div>Breast cancer is known as the most common type of cancer found in women and a leading cause of cancer death in women, with the global incidence only increasing. Breast cancer in Malaysia is also unfortunately the most prevalent in Malaysian women. Many treatment options are available for breast cancer, but there is increasing resistance developed against treatment and increased recurrence risk, emphasizing the need for new treatment options. This review will focus on the applications of phage display screening in the context of breast cancer. Phage display screening can facilitate the drug discovery process by providing rapid screening and isolation of peptides that bind to targets of interest with high specificity. Peptides derived from phage display target various types of proteins involved in breast cancer, including HER2, C5AR1, p53 and PRDM14, either for therapeutic or diagnostic purposes. Different approaches were employed as well to produce potential peptides using radiolabelling and conjugation techniques. Promising results were reported for <em>in vitro</em> and <em>in vivo</em> studies utilizing peptides derived from phage display screening. Further optimization of the protocols and factors to consider are required to mitigate the challenges involved with phage display screening of peptides for breast cancer diagnosis and treatment.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349488","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

Unveiling the intricate dance: Obesity and TNBC connection examined 揭开复杂舞蹈的面纱研究肥胖与 TNBC 的关系

IF 5.2 2区医学

Life sciences Pub Date : 2024-09-25 DOI: 10.1016/j.lfs.2024.123082

{"title":"Unveiling the intricate dance: Obesity and TNBC connection examined","authors":"","doi":"10.1016/j.lfs.2024.123082","DOIUrl":"10.1016/j.lfs.2024.123082","url":null,"abstract":"<div><div>Amid the dynamic field of cancer research, various targeted therapies have proven crucial in combating breast cancer, the most prevalent cancer among women globally. Triple Negative Breast Cancer (TNBC) stands out from other types of breast cancer due to the absence of three key receptors on the cell surface (progesterone, estrogen, and HER2). Researchers are working on finding ways to address TNBC's elusive biomarkers and minimize the damage caused by the disease through treatments like chemotherapies and targeted pathway receptors. One connection that should receive more attention is the link between TNBC and obesity. Obesity is defined as consuming significantly more energy than is expended, resulting in a high BMI. Moreover, obesity fosters a cancer-friendly environment characterized by inflammation, elevated levels of hormones, proteins, and signaling that activate pathways promoting cancer. Non-Hispanic black women have experienced notable disparities in TNBC rates. Various factors have led to the higher incidence and poorer outcomes of TNBC in non-Hispanic black women. This detailed review explores the complex relationship between obesity and TNBC, examining how the two disorders are connected in terms of disparities and offering a glimpse into future research and interventions.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142327516","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

DNA-PKcs modulates mouse lung homeostasis via the regulation of mitochondrial fission DNA-PKcs通过调控线粒体分裂调节小鼠肺稳态

IF 5.2 2区医学

Life sciences Pub Date : 2024-09-25 DOI: 10.1016/j.lfs.2024.123078

{"title":"DNA-PKcs modulates mouse lung homeostasis via the regulation of mitochondrial fission","authors":"","doi":"10.1016/j.lfs.2024.123078","DOIUrl":"10.1016/j.lfs.2024.123078","url":null,"abstract":"<div><h3>Background</h3><div>The role of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is multifaceted, paradoxically promoting both cell survival and cell death across multiple organs. However, its impact on lung homeostasis remains elusive. Here, we investigate the function of DNA-PKcs in mouse lungs, aiming to elucidate its role for lung abnormalities associated with DNA-PKcs deficiency.</div></div><div><h3>Materials and methods</h3><div>Histological assessment and immunohistochemistry were used to reveal the pathological changes of the lungs in DNA-PKcs-deficient mice. Transcriptomic analysis identified differentially expressed genes and pathways in DNA-PKcs-deficient lungs. Furthermore, mitochondrial dysfunction induced by DNA-PKcs deficiency was investigated by qPCR and immunoblotting. Mouse primary lung fibroblasts were used to evaluate the potential therapeutic effect of inhibiting mitochondrial fission with Mdivi-1.</div></div><div><h3>Key findings</h3><div>In DNA-PKcs-deficient mouse lungs, we observed pathological changes including alveolar septal thickening, capillary congestion and hemorrhage, along with lung cell proliferation. Transcriptome analysis revealed an upregulation of the reactive oxygen species (ROS) biosynthesis process and the apoptotic signaling pathway caused by DNA-PKcs deficiency. Further investigations demonstrated that DNA-PKcs deficiency led to mitochondrial dysfunction and increased oxidative stress, along with increased cell apoptosis in the mouse lungs. Notably, we detected enhanced phosphorylation of the mitochondrial fission protein DRP1 in DNA-PKcs-deficient mouse lungs. Intriguingly, inhibiting mitochondrial fission using Mdivi-1 suppressed cell death in primary mouse lung fibroblasts with siRNA-mediated DNA-PKcs knockdown.</div></div><div><h3>Significance</h3><div>Our study provides insights into the crucial role of DNA-PKcs in sustaining lung homeostasis via the maintenance of mitochondrial functionality and provides a therapeutic strategy targeting mitochondrial fission against DNA-PKcs deficiency-associated lung diseases.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349470","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

Tubulin interaction at tubulin-binding sequence 1 (TBS1) is required for proper surface expression and TRPV1 channel activity 正常的表面表达和 TRPV1 通道活性需要管蛋白结合序列 1 (TBS1) 上的管蛋白相互作用。

IF 5.2 2区医学

Life sciences Pub Date : 2024-09-25 DOI: 10.1016/j.lfs.2024.123070

{"title":"Tubulin interaction at tubulin-binding sequence 1 (TBS1) is required for proper surface expression and TRPV1 channel activity","authors":"","doi":"10.1016/j.lfs.2024.123070","DOIUrl":"10.1016/j.lfs.2024.123070","url":null,"abstract":"<div><div>TRPV1, a polymodal and nonselective cation channel has unique gating mechanisms which is regulated by supramolecular complexes at the plasma membrane formed with membrane proteins, lipids and kinase pathways. Crosstalk between microtubule cytoskeleton with TRPV1 at various level has been established. Previously we demonstrated that the positively-charged residues present at specific tubulin-binding stretch sequences (i.e. TBS1 and TBS2, AA 710–730 and 770–797 respectively) located at the C-terminus of TRPV1 are crucial for tubulin interaction and such sequences have evolutionary origin. The nature of TRPV1-tubulin complex and its functional importance remain poorly understood. Here, we made several mutations in the TBS1 and TBS2 regions and characterized such mutants. Though these mutations reduce tubulin interaction drastically, a low and basal-level of tubulin interaction remains with these mutants. Substitution of positively-charged residues (Lys and Arg) to Ala in the TBS1, but not in TBS2 region results in reduced ligand-sensitivity. Such ligand-sensitivity is altered in response to Taxol or Nocodazole. We suggest that tubulin interaction at the TBS1 region favours channel opening while interaction in TBS2 favours channel closure. We demonstrate for the first time the functional significance of TRPV1-tubulin complex and endorse microtubule dynamics as a parameter that can alter TRPV1 channel functions. These findings can be relevant for several physiological functions and also in the context of chemotherapy-induced neuropathic pain caused by various microtubule stabilizing chemotherapeutic drugs. Thus, this characterization may indicate TRPV1 as a potential therapeutic target relevant for chemotherapeutic drug-induced peripheral neuropathies, neurodegeneration and other neurological disorders.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349486","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

Hypoxia impairs male reproductive functions via inducing rat Leydig cell ferroptosis under simulated environment at altitude of 5000 m 在海拔 5000 米的模拟环境下，缺氧通过诱导大鼠睾丸髓质细胞铁蛋白沉积损害雄性生殖功能。

IF 5.2 2区医学

Life sciences Pub Date : 2024-09-25 DOI: 10.1016/j.lfs.2024.123076

{"title":"Hypoxia impairs male reproductive functions via inducing rat Leydig cell ferroptosis under simulated environment at altitude of 5000 m","authors":"","doi":"10.1016/j.lfs.2024.123076","DOIUrl":"10.1016/j.lfs.2024.123076","url":null,"abstract":"<div><h3>Aims</h3><div>Many studies demonstrated reproductive damage in men residing in plains who are exposed to hypoxia at high altitudes. However, little is known about mechanisms between male reproductive impairment and hypobaric hypoxia. Hypoxia is one of the reasons for the imbalance of cellular redox system. Ferroptosis, involved in many pathophysiological progresses, is an oxidative damage-related, iron-dependent regulated cell death, which needs exogenous inducer. In our study, we explored the mechanism between hypoxia and male reproductive dysfunction.</div></div><div><h3>Materials and methods</h3><div>Here, we established animal model simulating hypobaric hypoxia at an altitude of 5000 m and used ELISA, WB, qPCR, flow cytometry and etc. to obtain different results.</div></div><div><h3>Key findings</h3><div>The results demonstrated decrease of plasma testosterone (T) and free testosterone (FT) levels under hypoxia, meanwhile there's decline in sperm counts and sperm motility, coupled with increase in sperm malformation rates. Flow cytometry confirmed significant reduction in Leydig cell numbers. Prussian blue staining showed iron depositions in interstitial testis. Features of ferroptosis such as increased MDA (malondialdehyde) levels, reduced solute carrier family 7 member 11 (SLC7A11, xCT) and glutathione peroxidase 4 (GPX4) expression were observed in testis after hypoxic exposure. Further in vitro experiments, we observed that hypoxia suppressed xCT-GPX4 pathway and enhanced cellular ROS accumulation to lead Leydig cell proliferation activity decline.</div></div><div><h3>Significance</h3><div>Our findings firstly indicated that hypoxia leads to male reproductive dysfunction via inducing Leydig cell ferroptosis. This discovery may offer a potential intervention target for addressing male reproductive injuries under hypoxic conditions.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349484","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

Skeletal muscle-derived exosomes prevent osteoporosis by promoting osteogenesis 骨骼肌源性外泌体通过促进骨生成预防骨质疏松症

IF 5.2 2区医学

Life sciences Pub Date : 2024-09-24 DOI: 10.1016/j.lfs.2024.123079

{"title":"Skeletal muscle-derived exosomes prevent osteoporosis by promoting osteogenesis","authors":"","doi":"10.1016/j.lfs.2024.123079","DOIUrl":"10.1016/j.lfs.2024.123079","url":null,"abstract":"<div><div>Skeletal muscle and bone are the major organs for physical activity, in which there is a parallel correlation between muscle mass and bone density throughout a lifetime. Osteoporosis is a systemic bone metabolic disorder caused by reduced bone formation and increased bone resorption. Based on the metabolic symbiosis relationship between skeletal muscle and bone, we hypothesis that skeletal muscle secretory factors could play constructive roles in osteoporosis. Exosomes have been verified to transfer bioactive factors among cells. However, the role of skeletal muscle derived-exosomes (SM-Exos) in osteoporosis is still unclear. In this study, we performed neuromuscular electrical stimulation (NMES) intervention on denervated skeletal muscles and subsequently extracted exosomes (DN + ES-Exo) from the skeletal muscles, and then injected these DN + ES-Exo into sarco-osteoporotic rats through tail vein. In vitro studies, we cocultured SM-Exos from different states with differentiated MC3T3-E1 osteoblasts. In brief, our research findings demonstrate that SM-Exos could partially promote osteogenesis both in vivo and in vitro. Further, our findings indicate that skeletal muscle contraction induced by NMES can reverse the incidence of sarco-osteoporosis to a certain degree, and DN + ES-Exo contributes to the improvement in osteoporosis by facilitating osteoblast differentiation. Then, we revealed that NMES might regulate several miRNAs in skeletal muscle, the miRNAs that are encapsulated by SM-Exos might be involved in osteogenic differentiation in a network manner. All in all, this study confirmed the effect of NMES on sarco-osteoporosis and explored the role of SM-Exos in the improvement of osteoporosis, which provide an effective theoretical support for the physical therapy of clinical sarco-osteoporosis.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349490","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

Gamma-aminobutyric acid-mediated neuro-immune interactions in glioblastoma: Implications for prognosis and immunotherapy response 胶质母细胞瘤中γ-氨基丁酸介导的神经-免疫相互作用：对预后和免疫疗法反应的影响。

IF 5.2 2区医学

Life sciences Pub Date : 2024-09-23 DOI: 10.1016/j.lfs.2024.123067

{"title":"Gamma-aminobutyric acid-mediated neuro-immune interactions in glioblastoma: Implications for prognosis and immunotherapy response","authors":"","doi":"10.1016/j.lfs.2024.123067","DOIUrl":"10.1016/j.lfs.2024.123067","url":null,"abstract":"<div><h3>Aims</h3><div>This study aimed to investigate the role of gamma-aminobutyric acid (GABA) in the glioblastoma (GBM) tumor immune microenvironment (TIME) and its impact on prognosis and response to immunotherapy.</div></div><div><h3>Main methods</h3><div>This study employed single-cell RNA sequencing (scRNA-seq) to delineate the TIME of GBM, utilized non-negative matrix factorization (NMF) for GABA-associated cell clustering, and performed pseudotime analysis for cellular trajectories. Additionally, we integrated immunohistochemistry (IHC), immunofluorescence (IF), and protein-protein interaction <strong>(</strong>PPI) analysis to explore the regulatory mechanisms within the tumor microenvironment.</div></div><div><h3>Key findings</h3><div>The study identified distinct GABA-associated immune cell subtypes, particularly macrophages and T-cells, with unique gene expression and developmental trajectories. The development of the GABA-associated scoring model (GABAAS), introduced novel prognostic indicators, enhancing our ability to predict patient outcomes. This study also suggests that GABA-related genes, including NDRG2 and TIMP1, play a crucial role in immune modulation, with potential implications for immunotherapy responsiveness.</div></div><div><h3>Significance</h3><div>The findings underscore the potential of targeting GABA-related genes (NDRG2 and TIMP1) and M2 macrophage to reshape the glioblastoma immune landscape, offering a new frontier in personalized neuro-immunotherapy. This approach holds promise to counter individual tumor immunosuppressive mechanisms, enhancing patient outcomes.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349471","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

Effect of senolytic drugs in young female mice chemically induced to estropause 化学诱导雌性小鼠衰老药物的效果

IF 5.2 2区医学

Life sciences Pub Date : 2024-09-21 DOI: 10.1016/j.lfs.2024.123073

{"title":"Effect of senolytic drugs in young female mice chemically induced to estropause","authors":"","doi":"10.1016/j.lfs.2024.123073","DOIUrl":"10.1016/j.lfs.2024.123073","url":null,"abstract":"<div><h3>Aims</h3><div>This study aimed to assess metabolic responses and senescent cell burden in young female mice induced to estropause and treated with senolytic drugs.</div></div><div><h3>Main methods</h3><div>Estropause was induced by 4-vinylcyclohexene diepoxide (VCD) injection in two-month-old mice. The senolytics dasatinib and quercetin (D + Q) or fisetin were given by oral gavage once a month from five to 11 months of age.</div></div><div><h3>Key findings</h3><div>VCD-induced estropause led to increased body mass and reduced albumin concentrations compared to untreated cyclic mice, without affecting insulin sensitivity, lipid profile, liver enzymes, or total proteins. Estropause decreased catalase activity in adipose tissue but had no significant effect on other redox parameters in adipose and hepatic tissues. Fisetin treatment reduced ROS levels in the hepatic tissue of estropause mice. Estropause did not influence senescence-associated beta-galactosidase activity in adipose and hepatic tissues but increased senescent cell markers and fibrosis in ovaries. Senolytic treatment did not decrease ovarian cellular senescence induced by estropause.</div></div><div><h3>Significance</h3><div>Overall, the findings suggest that estropause leads to minor metabolic changes in young females, and the senolytics D + Q and fisetin had no protective effects despite increased ovarian senescence.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290422","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