{"title":"USP7-stabilised HIPK2 promotes high glucose-induced endothelial cell dysfunctions to accelerate diabetic foot ulcers.","authors":"Huimin Huang, Yangyong Huang","doi":"10.1080/13813455.2024.2376815","DOIUrl":"https://doi.org/10.1080/13813455.2024.2376815","url":null,"abstract":"<p><p><b>Background:</b> This study aimed to explore the molecular mechanism of homeodomain-interacting protein kinase 2 (HIPK2) in diabetic foot ulcers (DFU).</p><p><p><b>Methods:</b> High glucose (HG)-induced human umbilical vein endothelial cells (HUVECs) were used to construct DFU cell models. Cell functions were determined using CCK8 assay, EdU assay, flow cytometry, transwell assay, wound healing assay and tube formation assay. Quantitative real-time PCR and western blot were applied to measure the gene expression.</p><p><p><b>Results:</b> HG treatment suppressed HUVECs proliferation, invasion, migration, and angiogenesis, while enhanced apoptosis. HIPK2 was overexpressed in DFU patients, and its knockdown alleviated HG-induced HUVECs dysfunctions. USP7 stabilised HIPK2 protein by reducing its ubiquitination. USP7 overexpression promoted HG-induced HUVECs dysfunctions, and HIPK2 upregulation also reversed the regulation of USP7 knockdown on HG-induced HUVECs dysfunctions. USP7/HIPK2 axis inhibited the activity of PI3K/AKT pathway.</p><p><p><b>Conclusion:</b> Our study revealed that USP7-stabilised HIPK2 contributed to HG-induced HUVECs dysfunctions, thus accelerating DFU process.</p>","PeriodicalId":8331,"journal":{"name":"Archives of Physiology and Biochemistry","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vinicius Guzzoni, Isabel Cristina Mallosto Emerich de Abreu, Mariane Bertagnolli, Roberta Hack Mendes, Adriane Belló-Klein, Dulce Elena Casarini, Karin Flues, Geórgia Orsi Cândido, Janaína Paulini, Kátia De Angelis, Fernanda Klein Marcondes, Maria Cláudia Irigoyen, Tatiana Sousa Cunha
{"title":"Aerobic training increases renal antioxidant defence and reduces angiotensin II levels, mitigating the high mortality in SHR-STZ model.","authors":"Vinicius Guzzoni, Isabel Cristina Mallosto Emerich de Abreu, Mariane Bertagnolli, Roberta Hack Mendes, Adriane Belló-Klein, Dulce Elena Casarini, Karin Flues, Geórgia Orsi Cândido, Janaína Paulini, Kátia De Angelis, Fernanda Klein Marcondes, Maria Cláudia Irigoyen, Tatiana Sousa Cunha","doi":"10.1080/13813455.2024.2377381","DOIUrl":"https://doi.org/10.1080/13813455.2024.2377381","url":null,"abstract":"<p><strong>Objectve: </strong>The purpose of the research was to investigate the effects of aerobic training on renal function, oxidative stress, intrarenal renin-angiotensin system, and mortality of hypertensive and diabetic (SHR-STZ) rats.</p><p><strong>Materials and methods: </strong>Blood pressure, creatinine, urea levels, urinary glucose, urine volume, and protein excretion were reduced in trained SHR-STZ rats.</p><p><strong>Results: </strong>Aerobic training not only attenuated oxidative stress but also elevated the activity of antioxidant enzymes in the kid'ney of SHR-STZ rats. Training increased intrarenal levels of angiotensin-converting enzymes (ACE and ACE2) as well as the neprilysin (NEP) activity, along with decreased intrarenal angiotensin II (Ang II) levels. Aerobic training significantly improved the survival of STZ-SHR rats.</p><p><strong>Conclusion: </strong>The protective role of aerobic training was associated with improvements in the renal antioxidative capacity, reduced urinary protein excretion along with reduced intrarenal Ang II and increased NEP activity. These findings might reflect a better survival under the combined pathological conditions, hypertension, and diabetes.</p>","PeriodicalId":8331,"journal":{"name":"Archives of Physiology and Biochemistry","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Godwin Adakole Ujah, Emmanuel Oleba Ofutet, Catherine Ironya-Ogar Ukam, Precious Evangeline Omiunu, Emaediong Ufot Ackley, Iboro Godwin Japhet, Jane Charles Ntauko, Queen Comfort Clement, Racheal Atu, Victor Udo Nna
{"title":"Protective effect of <i>tert</i>-butylhydroquinone against cisplatin-induced hepatorenal injury via modulating oxidative stress, inflammation, and apoptosis.","authors":"Godwin Adakole Ujah, Emmanuel Oleba Ofutet, Catherine Ironya-Ogar Ukam, Precious Evangeline Omiunu, Emaediong Ufot Ackley, Iboro Godwin Japhet, Jane Charles Ntauko, Queen Comfort Clement, Racheal Atu, Victor Udo Nna","doi":"10.1080/13813455.2024.2376812","DOIUrl":"https://doi.org/10.1080/13813455.2024.2376812","url":null,"abstract":"<p><strong>Context: </strong>Cisplastin (CDDP) is a chemotherapeutic drug frequently used to manage a variety of cancers. However, its use is associated with hepatorenal toxicity resulting from elevated reactive oxygen species production.</p><p><strong>Objective: </strong>Herein, the hepatorenal protective effect of <i>tert</i>-butylhydroquinone (tBHQ) in cisplatin (CDDP)-treated rats was examined.</p><p><strong>Methods: </strong>Wistar male rats randomly divided into four groups: normal control, tBHQ, CDDP and tBHQ + CDDP received 50 mg/kg b.w./day of tBHQ orally for 14 days while 7 mg/kg b.w of CDDP was administered intraperitoneally on Day 8.</p><p><strong>Results: </strong>CDDP increased serum biomarkers of hepatic (AST, ALP, ALT, GGT) and renal (creatinine, urea, uric acid, kidney injury molecule 1) function. The levels of nuclear factor erythroid-2-related factor 2 protein and the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities were decreased in liver and kidney. Also, CDDP increased hepatic and renal levels of NF-κB, TNFα, Bax and caspase-3 proteins and decreased hepatorenal levels of Bcl-2 protein in the liver and kidney. Pre-treatment with tBHQ prevented these negative effects.</p><p><strong>Significance: </strong>Pre-intervention with tBHQ attenuates hepatorenal toxicity of CDDP by dampening oxidative stress, inflammation and apoptosis.</p>","PeriodicalId":8331,"journal":{"name":"Archives of Physiology and Biochemistry","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"METTL14 plays an oncogenic role in NSCLC by modulating ferroptosis and the m6A modification of GPX4.","authors":"Yang Lou, Kan Huang, Bo Xu, Xianguo Chen","doi":"10.1080/13813455.2024.2376813","DOIUrl":"https://doi.org/10.1080/13813455.2024.2376813","url":null,"abstract":"<p><strong>Context: </strong>N6-methyladenosine (m6A) of RNA is involved in the progression of non-small cell lung cancer (NSCLC).</p><p><strong>Objective: </strong>This study investigated the role of METTL14 in NSCLC and the mechanism.</p><p><strong>Materials and methods: </strong>Expression levels were assessed by quantitative real-time PCR and ELISA assays. Cells viability was assessed by cell counting kit-8. M6A methylation was analysed by methylated RNA immunoprecipitation (MeRIP), RIP, luciferase assay, and mRNA stability assay.</p><p><strong>Results: </strong>The results showed that METTL14 was highly expressed in NSCLC tissues and cell lines. Knockdown of METTL14 inhibited the cell viability while induced ferroptosis of NSCLC cells. Mechanistically, METTL14 interacts with GPX4, mediates m6A modification of GPX4, enhances its mRNA stability, and upregulates its expression. In addition, IGF2BP1 recognises the m6A-methylated GPX4 and mediates the elevated mRNA stability. Moreover, GPX4 reversed the effects of METTL14 depletion.</p><p><strong>Discussion and conclusion: </strong>The METTL14/GPX4 axis promotes NSCLC progression by inhibiting cell ferroptosis through the recognition of m6A modification mediated by IGF2BP1.</p>","PeriodicalId":8331,"journal":{"name":"Archives of Physiology and Biochemistry","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Behaviour of Tunisian <i>Psammomys obesus</i> fed high-calorie diets: biochemical disturbance and histopathological alterations.","authors":"Souhaieb Chrigui, Sihem Mbarek, Sameh Hadj Taieb, Zohra Haouas, Monssef Feki, Maha Benlarbi, Ayachi Zemmel, Fatiha Chigr, Nourhène Boudhrioua, Rafika Ben Chaouacha-Chekir","doi":"10.1080/13813455.2024.2375983","DOIUrl":"https://doi.org/10.1080/13813455.2024.2375983","url":null,"abstract":"<p><p>This work investigated the biochemical disturbances and histological alteration in <i>Psammomys obesus</i> animal model fed different high calorie diets (HCDs) during three months. Four diets were used: a low-calorie natural diet, <i>Chenopodiaceae</i> halophyte plant used as control (LCD), a high standard carbohydrate diet rich in protein, HCD 0, a high carbohydrate diet rich in two concentrations of fat, HCD 1 and HCD 2. All animals having received HCDs developed dyslipidemia after one month of experiment with distinction of different sub-groups developing or not obesity and diabetes. HCDs induced a remarkable increasing in blood cholesterol, LDL-cholesterol and triglyceride levels indicating a fast induction of dyslipidemia and a significant increase of aminotransaminases activities revealing a pronounced hepatotoxicity. Animal developing diabetes showed a severe hepatic injury, a degeneration of the adipose tissue and a significant reduction of retinal thickness. <i>P. obesus</i> seems to be an excellent animal model to investigate nutritional metabolic diseases.</p>","PeriodicalId":8331,"journal":{"name":"Archives of Physiology and Biochemistry","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Muhammed Haluk Ciftci, Vedat Turkoglu, Zehra Bas, Fatih Caglar Celikezen
{"title":"In vitro inhibitor effect and molecular docking of thiamine (vitamin B<sub>1</sub>), riboflavin (vitamin B<sub>2</sub>), and reference inhibitor captopril on angiotensin-converting enzyme purified from sheep plasma.","authors":"Muhammed Haluk Ciftci, Vedat Turkoglu, Zehra Bas, Fatih Caglar Celikezen","doi":"10.1080/13813455.2024.2376814","DOIUrl":"https://doi.org/10.1080/13813455.2024.2376814","url":null,"abstract":"<p><strong>Objective: </strong>Angiotensin-converting enzyme (ACE, EC 3.4.15.1) is a very important factor in the regulation of blood pressure. Also, the inhibition of ACE with natural compounds has been a very important research area in the treatment of high blood pressure. ACE was purified and characterized from sheep plasma. Molecular docking studies and the inhibition effect of thiamine, riboflavin, and captopril on ACE were investigated.</p><p><strong>Methods: </strong>Herein, ACE was purified from sheep plasma by affinity chromatography. The effect of thiamine and riboflavin on ACE was researched. Molecular docking studies were performed to understand the molecular interactions between thiamine, riboflavin, and captopril with ACE.</p><p><strong>Results: </strong>The purification coefficient was found to be 8636 fold. The binding energy of thiamine, riboflavin, and captopril was found to be -6.7 kcal/mol, -8.1 kcal/mol, and -5.5 kcal/mol, respectively. Thiamine conformed to three conventional hydrogen bonds with ASP:415, HIS:513, and LYS:454. Riboflavin formed four conventional hydrogen bonds with GLN:281, GLU:376, THR:282, and TYR:520. Captopril formed two conventional hydrogen bonds with ARG:124, one conventional hydrogen bond with TYR:62 and ASN:85, and one carbon-hydrogen bond with ASN:66. Molecular docking results showed that thiamine, riboflavin, and captopril interacted with ACE through hydrogen bonding and hydrophobic interactions. Thiamine and riboflavin indicated significant inhibition effects on ACE. The IC<sub>50</sub> values of thiamine, riboflavin, and captopril were found as 960.56 µM, 11.02 µM, and 1.60 nM, respectively. K<sub>i</sub> values for thiamine, riboflavin, and captopril were determined as 1352.04 µM, 12.30 µM, and 1.06 nM, respectively.</p><p><strong>Conclusion: </strong>In this work, it was concluded that thiamine and riboflavin may have preventive and therapeutical impacts against high blood pressure with their ACE inhibitor effect. Thiamine and riboflavin showed a lower inhibitory effect with a higher IC<sub>50</sub> than captopril. However, when the inhibitory effect of thiamine and riboflavin vitamins is compared to captopril, it is concluded that they may be natural inhibitors with fewer side effects.</p>","PeriodicalId":8331,"journal":{"name":"Archives of Physiology and Biochemistry","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hsa_circ_0004776 regulates the retina neovascularization in progression of diabetic retinopathy <i>via</i> hsa-miR-382-5p/<i>BDNF</i> axis.","authors":"Lu Ye, Yixiu Chen, Wendong Gu, Jun Shao, Yu Xin","doi":"10.1080/13813455.2024.2375981","DOIUrl":"10.1080/13813455.2024.2375981","url":null,"abstract":"<p><p>The aim of this work was to identify the regulatory function of hsa_circ_0004776 in the progression of diabetic retinopathy (DR). The direct interactions between hsa_circ_0004776 and hsa-miR-382-5p and between hsa-miR-382-5p and <i>BDNF</i>, were confirmed <i>via</i> dual-luciferase reporter assays. Quantitative Real-Time PCR analysis indicated that hsa_circ_0004776 was highly expressed in aqueous humour samples of DR patients and human retinal microvascular epithelial cells (hRECs) under a high-glucose environment, whereas hsa-miR-382-5p showed the opposite trend. Overexpressed hsa_circ_0004776 significantly enhanced DNA synthesis, proliferation, migration, and tube formation in hRECs in hyperglycaemia, while hsa-miR-382-5p mimics reversed these changes. Additionally, in a streptozotocin-induced Sprague-Dawley rat model of DR, vitreous microinjection of rno-miR-382-5p agomir reversed the pathologic features in the progression of DR, including retinal vascular leakage, capillary decellularization, loss of pericytes, fibrosis, and gliosis. Our results indicated that under hyperglycaemic conditions, hsa_circ_0004776 influences the progression of DR <i>via</i> hsa-miR-382-5p and thus represents a potential therapeutic target.</p>","PeriodicalId":8331,"journal":{"name":"Archives of Physiology and Biochemistry","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaosi Hong, Leiqin Cai, Lanlan Li, Dinghao Zheng, Jianghong Lin, Zhuoxian Liang, Wan Fu, Diefei Liang, Tingting Zeng, Kan Sun, Wei Wang, Sifan Chen, Meng Ren, Li Yan
{"title":"Keratinocyte-derived small extracellular vesicles delay diabetic wound healing by triggering fibroblasts autophagy.","authors":"Xiaosi Hong, Leiqin Cai, Lanlan Li, Dinghao Zheng, Jianghong Lin, Zhuoxian Liang, Wan Fu, Diefei Liang, Tingting Zeng, Kan Sun, Wei Wang, Sifan Chen, Meng Ren, Li Yan","doi":"10.1080/13813455.2024.2358020","DOIUrl":"https://doi.org/10.1080/13813455.2024.2358020","url":null,"abstract":"<p><p>Keratinocyte and fibroblast dysfunctions contribute to delayed healing of diabetic wounds. Small extracellular vesicles (sEV) are key mediators of intercellular communication and are involved in the pathogenesis of several diseases. Recent findings suggest that sEV derived from high-glucose-treated keratinocyte (HaCaT-HG-sEV) can transport LINC01435 to inhibit tube formation and migration of HUVECs, thereby delaying wound healing. This study aimed to elucidate sEV-related communication mechanisms between keratinocytes and fibroblasts during diabetic wound healing. HaCaT-HG-sEV treatment and LINC01435 overexpression significantly decreased fibroblast collagen level and migration ability but significantly increased fibroblast autophagy. However, treatment with an autophagy inhibitor suppressed LINC01435 overexpression-induced decrease in collagen levels in fibroblasts. In diabetic mice, HaCaT-HG-sEV treatment decreased collagen levels and increased the expression of the autophagy-related proteins Beclin-1 and LC3 at the wound site, thereby delaying wound healing. Conclusively, LINC01435 in keratinocyte-derived sEV activates fibroblast autophagy and reduces fibroblast collagen synthesis, leading to impaired diabetic wound healing.</p>","PeriodicalId":8331,"journal":{"name":"Archives of Physiology and Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anmar Al-Taie, Oritsetimeyin Arueyingho, Jalal Khoshnaw, Abdul Hafeez
{"title":"Clinical outcomes of multidimensional association of type 2 diabetes mellitus, COVID-19 and sarcopenia: an algorithm and scoping systematic evaluation.","authors":"Anmar Al-Taie, Oritsetimeyin Arueyingho, Jalal Khoshnaw, Abdul Hafeez","doi":"10.1080/13813455.2022.2086265","DOIUrl":"10.1080/13813455.2022.2086265","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to provide a scoping and comprehensive review for the clinical outcomes from the cross-link of Type 2 diabetes mellitus (T2DM), COVID-19, and sarcopenia.</p><p><strong>Methods: </strong>By using PRISMA guidelines and searching through different databases that could provide findings of evidence on the association of T2DM, COVID-19, and sarcopenia.</p><p><strong>Results: </strong>Thirty-three studies reported a relationship between sarcopenia with T2DM, twenty-one studies reported the prognosis COVID-19 in patients with T2DM, ten studies reported the prognosis of COVID-19 in patients with sarcopenia, five studies discussed the outcomes of sarcopenia in patients with COVID-19, and one study reported sarcopenia outcomes in the presence of T2DM and COVID-19.</p><p><strong>Conclusion: </strong>There is an obvious multidimensional relationship between T2DM, COVID-19 and sarcopenia which can cause prejudicial effects, poor prognosis, prolonged hospitalisation, lowered quality of life and a higher mortality rate during the current COVID-19 pandemic.</p>","PeriodicalId":8331,"journal":{"name":"Archives of Physiology and Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47405476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mona N BinMowyna, Nora A AlFaris, Ekram A Al-Sanea, Jozaa Z AlTamimi, Tahany S Aldayel
{"title":"Resveratrol attenuates against high-fat-diet-promoted non-alcoholic fatty liver disease in rats mainly by targeting the miR-34a/SIRT1 axis.","authors":"Mona N BinMowyna, Nora A AlFaris, Ekram A Al-Sanea, Jozaa Z AlTamimi, Tahany S Aldayel","doi":"10.1080/13813455.2022.2046106","DOIUrl":"10.1080/13813455.2022.2046106","url":null,"abstract":"<p><p>This study evaluated if miR-34a/SIRT1 signalling mediates the anti-hepatosteatotic effect of resveratrol (RSV) in high-fat-diet (HFD)-fed rats. Rats were divided into seven groups (<i>n</i> = 6/each) as control, control + miR-34a agomir negative control, HFD, HFD + miR-34a, HFD + RSV, HFD + RSV + Ex-527 (a SIRT1 inhibitor), and HFD + RSV + miR-34a agomir. After 8 weeks, RSV suppressed dyslipidemia, lowered fasting glucose and insulin levels, improved insulin sensitivity, and prevented hepatic lipid accumulation. These effects were associated with hepatic downregulation of SREBP1 and SREBP2, upregulation of PPARα, and acetylation of Nrf2 (activation) and NF-κβ p65 (inhibition). Also, RSV reduced the transcription of miR-34a and increased the nuclear localisation of SIRT1 in the livers, muscles, and adipose tissues of HFD-fed rats. All these effects were prevented by EX-527 and miR-34a agmir. In conclusion, RSV prevents HFD-induced insulin resistance and hepatic steatosis by suppressing miR-34a-induced activation of SIRT1.</p>","PeriodicalId":8331,"journal":{"name":"Archives of Physiology and Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41872699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}