Life sciences最新文献

Biochanin A-mediated anti-ferroptosis is associated with reduction of septic kidney injury 生物钱币素 A 介导的抗铁细胞生成与减轻脓毒性肾损伤有关

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-11 DOI: 10.1016/j.lfs.2024.123124

{"title":"Biochanin A-mediated anti-ferroptosis is associated with reduction of septic kidney injury","authors":"","doi":"10.1016/j.lfs.2024.123124","DOIUrl":"10.1016/j.lfs.2024.123124","url":null,"abstract":"<div><h3>Aims</h3><div>This study aimed to investigate the therapeutic potential of biochanin A in a sepsis associated- acute kidney injury (SA-AKI) mouse model induced by lipopolysaccharide (LPS).</div></div><div><h3>Main methods</h3><div>Male BALB/C mice (n = 7 per group) were injected with biochanin A (40 mg/kg, i.p.) or ferrostatin-1 (5 mg/kg, i.p.) in the presence or absence of LPS (10 mg/kg, i.p.). Survival rates were monitored twice a day for up to 2 weeks. Morphologic and functional changes in kidney tissue were assessed by H&E staining and by analyzing of levels of blood-urea nitrogen (BUN) and creatinine (CR) in serum, respectively. Kidney epithelial cell death was analyzed by TUNEL staining, Prussian blue staining, iron quantification, lipid peroxide quantification, and glutathione quantification. Anti-ferroptosis mechanism of biochanin A was analyzed by RNA sequencing in mouse embryonic fibroblast cells.</div></div><div><h3>Key findings</h3><div>Biochanin A increased the survival rate of septic mice and inhibited the secretion of high mobility group box 1, an important inflammatory mediator in sepsis. Biochanin A inhibited LPS-induced kidney damage by suppressing dilatation and kidney tubular epithelial cell death. Furthermore, serum levels of BUN and CR were reduced in biochanin A-treated endotoxemic mice. Biochanin A inhibited the accumulation of iron and lipid peroxide and prevented glutathione depletion in the kidney tissue. Also, nine genes associated with the anti-ferroptosis effects of biochanin A were identified by RNA sequencing analysis.</div></div><div><h3>Significance</h3><div>The present study suggests that biochanin A is an effective inhibitor of ferroptosis, representing a potential treatment or prophylactic for sepsis-related disorders such as SA-AKI.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433923","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

Schwann cell autotransplantation for the treatment of peripheral nerve injury 用于治疗周围神经损伤的许旺细胞自体移植。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-10 DOI: 10.1016/j.lfs.2024.123129

引用次数: 0

Sodium selenite inhibits cervical cancer progression via ROS-mediated suppression of glucose metabolic reprogramming 亚硒酸钠通过 ROS 介导的葡萄糖代谢重编程抑制宫颈癌的进展。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-09 DOI: 10.1016/j.lfs.2024.123109

{"title":"Sodium selenite inhibits cervical cancer progression via ROS-mediated suppression of glucose metabolic reprogramming","authors":"","doi":"10.1016/j.lfs.2024.123109","DOIUrl":"10.1016/j.lfs.2024.123109","url":null,"abstract":"<div><h3>Aims</h3><div>This study aims to explore the inhibitory effect of selenium on cervical cancer through suppression of glucose metabolic reprogramming and its underlying mechanisms.</div></div><div><h3>Methods</h3><div>Sodium selenite (SS) treated HeLa and SiHa cells were assessed for proliferation using the CCK-8 assay and immunofluorescence. DNA synthesis was measured with the EdU assay. A nude mouse xenograft model evaluated SS's anti-cervical cancer effects. Reactive oxygen species (ROS) and mitochondrial membrane potential were measured using flow cytometry, DCFH-DA, and JC-1 probes, respectively. Apoptosis was detected via Annexin V/PI staining and Western blot. Glucose uptake, lactate production, and ATP generation were determined using 2-NBDG probes and assay kits. The mRNA and protein levels of glycolysis-related genes HK2, GLUT1, and PDK1 were measured using RT-qPCR and Western blot.</div></div><div><h3>Key findings</h3><div>SS inhibited HeLa and SiHa cells viability in a dose- and time-dependent manner. Intraperitoneal injection of SS in nude mice significantly inhibited HeLa cell xenograft growth without evident hepatotoxicity or nephrotoxicity. SS inhibited glucose metabolic reprogramming in cancer cells primarily via ROS-mediated AKT/mTOR/HIF-1α pathway inhibition. Pretreatment with <em>N</em>-acetylcysteine (NAC) or MHY1485 (an mTOR activator) partially reversed the inhibitory effects of SS on glucose metabolic reprogramming, cell proliferation, and migration, as well as its pro-apoptotic effects.</div></div><div><h3>Significance</h3><div>SS exhibited anti-cervical cancer effects, likely through the induction of ROS generation and inhibition of glucose metabolic reprogramming in cervical cancer cells, thereby inhibiting cell proliferation and promoting apoptosis. These findings provide new insights into understanding the molecular mechanisms underlying SS for potential new drug development for cervical cancer.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391646","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

Enhanced oxidative stress aggravates BLM-induced pulmonary fibrosis by promoting cellular senescence through enhancing NLRP3 activation. 氧化应激的增强通过加强 NLRP3 的激活促进细胞衰老，从而加重 BLM 诱导的肺纤维化。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-09 DOI: 10.1016/j.lfs.2024.123128

Jiukang Feng, Hui Liu, Kewei Jiang, Xinyu Gong, Rong Huang, Chao Zhou, Jiali Mao, Yuanli Chen, Hongmei Xu, Xiaoming Zhang, Xiaoxiao Yang, Dahai Zhao

{"title":"Enhanced oxidative stress aggravates BLM-induced pulmonary fibrosis by promoting cellular senescence through enhancing NLRP3 activation.","authors":"Jiukang Feng, Hui Liu, Kewei Jiang, Xinyu Gong, Rong Huang, Chao Zhou, Jiali Mao, Yuanli Chen, Hongmei Xu, Xiaoming Zhang, Xiaoxiao Yang, Dahai Zhao","doi":"10.1016/j.lfs.2024.123128","DOIUrl":"https://doi.org/10.1016/j.lfs.2024.123128","url":null,"abstract":"<p><strong>Aims: </strong>Idiopathic pulmonary fibrosis (IPF) is a disease associated with aging, where increased oxidative stress accelerates the progression of pulmonary fibrosis (PF). The specific mechanisms through which oxidative stress intensifies PF are still not fully understood.</p><p><strong>Materials and methods: </strong>In this study, we used bleomycin (BLM)-induced PF mouse model and TGF-β-induced collagen deposition cells for in vivo and in vitro experiments, respectively. Additionally, we employed BSO, a glutathione synthesis inhibitor, to induce excess ROS.</p><p><strong>Key findings: </strong>Our findings revealed that heightened ROS production significantly exacerbated PF development in mice and increased collagen deposition in A549 cells. We also showed that cellular senescence was further intensified by the combined treatment of BSO with BLM or TGF-β, as indicated by the increased levels of p53 and p21, along with an increase in β-galactosidase-positive cells. Moreover, inflammatory responses, including inflammatory cells, inflammatory cytokines, and ROS levels were dramatically increased with the BSO and BLM or TGF-β combination. Mechanistically, we found that NLRP3 inflammasome was activated more significantly by the combined treatments of BSO with BLM or TGF-β. Inhibition of NLRP3 ameliorated the aging-related phenotype and reduced p53 and p21 expression. Furthermore, we showed that N-acetylcysteine (NAC) treatment significantly attenuated BLM or BLM plus BSO-enhanced PF in vivo.</p><p><strong>Significance: </strong>Our study demonstrates that elevated ROS levels contribute to the development of PF via NLRP3-mediated cellular senescence. We also provide that targeting oxidative stress might be an effective strategy for treating PF.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406585","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

Zinc pyrithione ameliorates colitis in mice by interacting on intestinal epithelial TRPA1 and TRPV4 channels 吡啶硫酮锌通过与肠上皮 TRPA1 和 TRPV4 通道相互作用，缓解小鼠结肠炎。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-09 DOI: 10.1016/j.lfs.2024.123090

{"title":"Zinc pyrithione ameliorates colitis in mice by interacting on intestinal epithelial TRPA1 and TRPV4 channels","authors":"","doi":"10.1016/j.lfs.2024.123090","DOIUrl":"10.1016/j.lfs.2024.123090","url":null,"abstract":"<div><h3>Aims</h3><div>Although zinc pyrithione (ZPT) has been studied as topical antimicrobial and cosmetic consumer products, little is known about its pharmacological actions in gastrointestinal (GI) health and inflammation. Our aims were to investigate the effects of ZPT on transient receptor potential (TRP) channels and Ca<sup>2+</sup> signaling in intestinal epithelial cells (IECs) and its therapeutic potential for colitis.</div></div><div><h3>Main methods</h3><div>Digital Ca<sup>2+</sup> imaging and patch-clamp electrophysiology were performed on human colonic epithelial cells (HCoEpiC) and rat small intestinal epithelial cells (IEC-6). The transcription levels of proinflammatory cytokines such as IL-1β were detected by RTq-PCR. Dextran sulfate sodium (DSS) was used to induce colitis in mice.</div></div><div><h3>Key findings</h3><div>ZPT dose-dependently induced Ca<sup>2+</sup> signaling and membrane currents in IECs, which were attenuated by selective blockers of transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 4 (TRPV4) channels, respectively. Interestingly, Ca<sup>2+</sup> entry via TRPA1 channels inhibited the activity of TRPV4 channels in HCoEpiC, but not vice versa. ZPT significantly promoted migration of IECs by activating TRPA1 and TRPV4 channels. ZPT reversed lipopolysaccharides (LPS)-induced changes in mRNA expression of TRPA1 and TRPV4. Moreover, ZPT decreased mRNA levels of pro-inflammatory factors promoted by LPS in HCoEpiC, which were restored by selective TRPA1 blocker. In whole animal studies in vivo, ZPT significantly ameliorated DSS-induced body weight loss, colon shortening and increases in stool score, serum calprotectin and lactic acid (LD) in mouse model of colitis.</div></div><div><h3>Significance</h3><div>ZPT exerts anti-colitic action likely by anti-inflammation and pro-mucosal healing through TRP channels in IECs. The present study not only expands pharmacology spectrum of ZPT in GI tract, but also repurposes it to a potential drug for colitis therapy.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391650","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

Navigating therapeutic prospects by modulating autophagy in colorectal cancer 通过调节结直肠癌中的自噬作用探索治疗前景。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-09 DOI: 10.1016/j.lfs.2024.123121

{"title":"Navigating therapeutic prospects by modulating autophagy in colorectal cancer","authors":"","doi":"10.1016/j.lfs.2024.123121","DOIUrl":"10.1016/j.lfs.2024.123121","url":null,"abstract":"<div><div>Colorectal cancer (CRC) remains a leading cause of death globally despite the improvements in cancer treatment. Autophagy is an evolutionarily conserved lysosomal-dependent degradation pathway that is critical in maintaining cellular homeostasis. However, in cancer, autophagy may have conflicting functions in preventing early tumour formation versus the maintenance of advanced-stage tumours. Defective autophagy has a broad and dynamic effect not just on cancer cells, but also on the tumour microenvironment which influences tumour progression and response to treatment. To add to the layer of complexity, somatic mutations in CRC including tumour protein p53 (TP53), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), Kirsten rat sarcoma viral oncogene homolog (KRAS), and phosphatase and tensin homolog (PTEN) can render chemoresistance by promoting a pro-survival advantage through autophagy. Recent studies have also reported autophagy-related cell deaths that are distinct from classical autophagy by employing parts of the autophagic machinery, which impacts strategies for autophagy regulation in cancer therapy. This review discusses the molecular processes of autophagy in the evolution of CRC and its role in the tumour microenvironment, as well as prospective therapeutic methods based on autophagy suppression or promotion. It also highlights clinical trials using autophagy modulators for treating CRC, underscoring the importance of autophagy regulation in CRC therapy.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400692","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 effect of m6A methyltransferase METTL3 mediated TMEM30A regulation on tumor energy metabolism and cisplatin anti-tumor activity in oral squamous cell carcinoma. m6A甲基转移酶METTL3介导的TMEM30A调控对口腔鳞状细胞癌肿瘤能量代谢和顺铂抗肿瘤活性的影响

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-08 DOI: 10.1016/j.lfs.2024.123122

Wei Yuan, Shaobo Ouyang, Qiaoli Lv, Lan Liao

{"title":"The effect of m6A methyltransferase METTL3 mediated TMEM30A regulation on tumor energy metabolism and cisplatin anti-tumor activity in oral squamous cell carcinoma.","authors":"Wei Yuan, Shaobo Ouyang, Qiaoli Lv, Lan Liao","doi":"10.1016/j.lfs.2024.123122","DOIUrl":"https://doi.org/10.1016/j.lfs.2024.123122","url":null,"abstract":"<p><strong>Aims: </strong>Cisplatin (CDDP) is still one of the most commonly used first-line treatments for advanced and recurrent oral squamous cell carcinoma patients in clinical practice. However, the decrease in tumor sensitivity to CDDP weakens its therapeutic effect. There is still limited research on the effect of METTL3-mediated methylation of m6A on CDDP sensitivity in oral squamous cell carcinoma (OSCC). TMEM30A widely exists in biomembranes and regulates the lipid asymmetry of the membrane, but there is no report on its function in OSCC. This study aims to explore the specific mechanism by which METTL3 regulates m6A methylation of TMEM30A and affects the occurrence and development of OSCC, and further investigate the effects of METTL3 and TMEM30A on the anti-tumor activity of CDDP.</p><p><strong>Key findings: </strong>In oral squamous cell carcinoma, METTL3 plays a pro cancer role and weakens the anti-tumor efficacy of CDDP; METTL3 positively regulates the expression of TMEM30A by m6A methylation modification and binding to TMEM30A; The abnormally high expression of TMEM30A in tumors not only weakens CDDP sensitivity, but also enhances the malignant evolution of cancer cells, regulates the metabolic balance of ATP and lactate in cells, and is a potential oncogenic gene.</p><p><strong>Significance: </strong>TMEM30A promotes malignant progression of tumors through METTL3 mediated m6A methylation modification, participates in maintaining the balance of tumor ATP and lactate metabolism, and thus reduces the anti-tumor activity of CDDP. TMEM30A is a potential gene target for CDDP anti-tumor activity in OSCC.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400693","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

Tyrosine hydroxylase-positive neurons in the rostral ventrolateral medulla mediate sympathetic activation in sepsis. 酪氨酸羟化酶阳性神经元在脓毒症中介导交感神经的激活。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-07 DOI: 10.1016/j.lfs.2024.123118

Yuan Mi, Hao Yu, PingWang, Yuxin Miao, Xu Teng, Sheng Jin, Lin Xiao, Hongmei Xue, Danyang Tian, Qi Guo, Yuming Wu

{"title":"Tyrosine hydroxylase-positive neurons in the rostral ventrolateral medulla mediate sympathetic activation in sepsis.","authors":"Yuan Mi, Hao Yu, PingWang, Yuxin Miao, Xu Teng, Sheng Jin, Lin Xiao, Hongmei Xue, Danyang Tian, Qi Guo, Yuming Wu","doi":"10.1016/j.lfs.2024.123118","DOIUrl":"https://doi.org/10.1016/j.lfs.2024.123118","url":null,"abstract":"<p><strong>Aim: </strong>Sepsis results in high mortality and is associated with organ dysfunction caused by infection. The present study aimed to elucidate whether early-stage sympathetic activation is associated with the prognosis of sepsis and its possible mechanisms.</p><p><strong>Methods: </strong>Patients with sepsis and healthy controls were included. Sepsis in rats was induced by lipopolysaccharide. Dexmedetomidine, a α2-adrenergic receptor agonist, was used in patients and rats with sepsis to evaluate the role of the sympathetic nervous system in sepsis. Holter monitoring was used to detect heart rate variability, while plasma samples were obtained to measure levels of norepinephrine and inflammatory markers. Mean arterial pressure, heart rate, and renal sympathetic nerve activity were recorded. Immunofluorescence was used to detect the activation of neurons in the rostral ventrolateral medulla (RVLM).</p><p><strong>Results: </strong>In patients with sepsis, plasma levels of norepinephrine and interleukin-1β were higher compared with those in controls and positively correlated with acute physiology and chronic health evaluation (APACHEII). SDNN and SDANN were significantly reduced as well as negatively correlated with APACHEII. Meanwhile, rats with sepsis showed increased of sympathetic outflow and plasma levels of norepinephrine, with increased c-fos levels in the RVLM. Treatment with dexmedetomidine could improve prognosis. Lesion of tyrosine hydroxylase-positive neurons in the RVLM attenuated sympathetic activation and target organs damage in septic rats as well as improved survival.</p><p><strong>Conclusion: </strong>The results suggest that tyrosine hydroxylase-positive neurons in the RVLM might contribute to the prognosis of sepsis via activation of the sympathetic nervous system, while dexmedetomidine could ameliorate sepsis via inhibiting sympathetic activation.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391647","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

Unravelling the interplay between ER stress, UPR and the cGAS-STING pathway: Implications for osteoarthritis pathogenesis and treatment strategy 揭示 ER 应激、UPR 和 cGAS-STING 通路之间的相互作用：对骨关节炎发病机制和治疗策略的影响。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-06 DOI: 10.1016/j.lfs.2024.123112

{"title":"Unravelling the interplay between ER stress, UPR and the cGAS-STING pathway: Implications for osteoarthritis pathogenesis and treatment strategy","authors":"","doi":"10.1016/j.lfs.2024.123112","DOIUrl":"10.1016/j.lfs.2024.123112","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a debilitating chronic degenerative disease affecting the whole joint organ leading to pain and disability. Cellular stress and injuries trigger inflammation and the onset of pathophysiological changes ensue after irreparable damage and inability to resolve inflammation, impeding the completion of the healing process. Extracellular matrix (ECM) degradation leads to dysregulated joint tissue metabolism. The reparative effort induces the proliferation of hypertrophic chondrocytes and matrix protein synthesis. Aberrant protein synthesis leads to endoplasmic reticulum (ER) stress and chondrocyte apoptosis with consequent cartilage matrix loss. These events in a vicious cycle perpetuate inflammation, hindering the restoration of normal tissue homeostasis. Recent evidence suggests that inflammatory responses and chondrocyte apoptosis could be caused by the activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signalling axis in response to DNA damage. It has been reported that there is a crosstalk between ER stress and cGAS-STING signalling in cellular senescence and other diseases. Based on recent evidence, this review discusses the role of ER stress, Unfolded Protein Response (UPR) and cGAS-STING pathway in mediating inflammatory responses in OA.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391648","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

Metformin's cardioprotective role in isoprenaline-induced myocardial infarction: Unveiling insights into the AMPK, NF-κB, JAK2/STAT3 pathways, and cholinergic regulation 二甲双胍在异丙肾上腺素诱发的心肌梗死中的心脏保护作用：揭示 AMPK、NF-κB、JAK2/STAT3 通路和胆碱能调节的奥秘。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-05 DOI: 10.1016/j.lfs.2024.123115

{"title":"Metformin's cardioprotective role in isoprenaline-induced myocardial infarction: Unveiling insights into the AMPK, NF-κB, JAK2/STAT3 pathways, and cholinergic regulation","authors":"","doi":"10.1016/j.lfs.2024.123115","DOIUrl":"10.1016/j.lfs.2024.123115","url":null,"abstract":"<div><h3>Aim</h3><div>Despite advancements in treatment modalities, myocardial infarction (MI) remains a significant global cause of mortality and morbidity. Metformin (MET), a commonly used antidiabetic medication, has demonstrated potential in various cardioprotective mechanisms. This study investigated whether MET could alleviate the histopathological, electrocardiographic, and molecular consequences of MI in rats.</div></div><div><h3>Materials and methods</h3><div>The study hypothesis was tested using an isoprenaline (ISOP)-induced MI model, where male Wistar rats were injected with ISOP (85 mg/kg/day, s.c., for 2 days) and treated with MET at the doses of 500 and 1000 mg/kg/day for 18 days or left untreated.</div></div><div><h3>Key findings</h3><div>ISOP-treated rats exhibited several indicators of MI, including significant ST-segment depression and prolonged QT-intervals on ECGs, worsened left ventricular histopathology with increased inflammatory cell infiltration, reduced expression of cardiac CHRM2, a cardioprotective cholinergic receptor, adaptive increases in AMPK and α7nAchR levels, and elevated levels of iNOS, NO, STAT3, JAK2, IL-6, TNF-α, and NF-κB. These effects were attenuated in rats treated with either low or high doses of MET. MET administration restored normal ECG recordings, diminished oxidative stress and inflammatory mediators, and downregulated NF-κB expression. Moreover, MET improved CHRM2 expression and normalized α7nAchR levels. Additionally, MET influenced the expression of key signaling molecules such as Akt, STAT3, and JAK2.</div></div><div><h3>Significance</h3><div>These findings might suggest that MET exerts cardioprotective effects in ISOP-induced MI in rats by mitigating critical inflammatory signaling pathways and regulating protective cholinergic mechanisms in the heart.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381237","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