Archives of Physiology and Biochemistry最新文献

Vitexin, a polyphenolic flavonoid, has been reported to be traditionally applied in the treatment of diabetes, cancer and cardiovascular diseases.

Objective: The aim of this study was to investigate the anti-apoptosis and anti-oxidation effect and the potential mechanism of vitexin on high glucose-induced HUVECs.

Materials and methods: A high dose of glucose was added to HUVECs to establish an in vitro model. The cell viability was detected by CCK8 and flow cytometry assays. 2,7-dichlorodihydrofluorescein diacetate, colorimetry, and enzyme-linked immunosorbent assay were performed to detect oxidative stress. Besides, top flash and western blotting were employed to evaluate the effect of vitexin on Wnt/β-catenin. Furthermore, a Wnt/β-catenin inhibitor (KYA1797K) was used to confirm whether Wnt/β-catenin is involved in the protection of vitexin. At the same time, RT-PCR and western blot were performed to determine the effect of vitexin on Nrf2, while immunofluorescence assays were employed for the assessment of Nrf2 localisation. Then, in order to validate that Nrf2 plays an important role in the anti-oxidant effect of vitexin, methods were utilised to silence Nrf2 gene.

Results: Herein, vitexin inhibited the proliferation and apoptosis of HG-mediated HUVECs. Mechanically, vitexin disrupted Wnt/β-catenin signalling pathway, thus resulting in the decrease of apoptosis in HG-induced HUVECs. A Wnt/β-catenin inhibitor (KYA1797K), was used for reverse verification. In the meantime, vitexin administration decreased reactive oxygen species (ROS) production and malondialdehyde (MDA) content and increased superoxide dismutase (SOD) activity in HG-induced HUVECs. Further investigations have revealed vitexin activated Nrf2 in HUVEC under high glucose, which was involved in its anti-oxidant effects.

Conclusion: Our investigation demonstrated that vitexin protected HUVECs from high glucose-induced injury via up-regulation of Wnt/β-catenin and Nrf2 signalling pathway. These results suggested that vitexin might serve as a potential drug for atherosclerosis and cardiovascular complications of diabetes.

This study evaluated if salidroside (SAL) alleviates high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) by downregulating miR-21. Rats (n = 8/group) were treated for 12 weeks as normal diet (control/ND), ND + agmoir negative control (NC) (150 µg/kg), ND + SAL (300 mg/kg), HFD, HFD + SAL, HFD + compound C (an AMPK inhibitor) (200 ng/kg), HFD + SAL + NXT629 (a PPAR-α antagonist) (30 mg/kg), and HFD + SAL + miR-21 agomir (150 µg/kg). SAL improved glucose and insulin tolerance and preserved livers in HFD-fed rats. In ND and HFD-fed rats, SAL reduced levels of serum and hepatic lipids and the hepatic expression of SREBP1, SREBP2, fatty acid (FA) synthase, and HMGCOAR. It also activated hepatic Nrf2 and increased hepatic/muscular activity of AMPK and levels of PPARα. All effects afforded by SAL were prevented by CC, NXT629, and miR-21 agmoir. In conclusion, activation of AMPK and upregulation of PPARα mediate the anti-steatotic effect of SAL.

Context: Patients with inflammatory bowel disease (IBD) were found to have the higher intestinal expression of Angiotensin-Converting Enzyme2 (ACE2) that could consequently increase susceptibility to COVID-19 infection.Objective: This study reports the outcomes of COVID-19 infection in a large cohort of IBD patients. We compare levels of serum ACE and IFN-α between COVID19 patients with and without IBD. We performed a cross-sectional retrospective multicenter study.Methods: We enrolled patients with IBD screened for SARS-COV-2 in six medical centres in Iran from June to November 2020. The blood samples were drawn to measure COVID-19 IgM and IgG, and serum levels of sACE2, sACE1, and interferon-α, regardless of suspicious symptoms have done the molecular test.Results: A total of 534 IBD patients were included in the study. Of these, 109 (20.0%) cases had detectable IgG and IgM against SARS-CoV-2. sACE2 levels were higher in IBD patients than controls, whereas ACE1and IFN-α levels were similar among groups.

Aims: To explore the interaction of TGFβ regulatory microRNAs (miRNAs) with different severities of diabetic kidney disease (DKD).

Methods: According to different UACR (30 and 300 mg/g), 436 subjects were included, and high glucose induced RMCs were cultured. Real-time PCR, ELISA, and automatic biochemical analysis were used to measure miRNAs, TGFβ1, and other biochemical indicators in serum and RMCs. Target genes of miRNA were predicted and visualised by bioinformatics.

Results: HbA1c, TGFβ1, miR-217, and miR-224 in T2DM patients increased with UACR, while miR-192 and miR-216a decreased. Ln UACR was positively correlated with HbA1c, TGFβ1, miR-217, and miR-224, and negatively correlated with miR-192 and miR-216a. High glucose and TGFβ1 affected miRNAs and these miRNAs affected each other. The miRNA target genes mainly revolve around PTEN, PI3K/Akt, and MAPK signalling pathways.

Conclusion: TGFβ regulatory miRNAs and different severity of DKD have a potential interaction regulating fibrosis through PTEN, PI3K/Akt, and MAPK pathways.

The aim of this meta-analysis was to assess the effects of almond consumption on the lipid profiles of type 2 diabetes mellitus (T2DM) patients. Eligible trials were searched from four electronic databases until Jan 2020. Five eligible articles were included in the final quantitative analysis. Overall, meta-analysis could not show any beneficial effect of almond consumption on total cholesterol (TC) weighted mean difference (WMD: 0.65 mg/dL, 95% CI: -7.52-8.82, p = .87), triglyceride (TG; WMD: 1.59 mg/dL, 95% CI: -21.77-24.96, p = .89), low-density lipoprotein cholesterol (LDL-C; WMD: -5.40 mg/dL, 95% CI: -13.30-2.50, p = .18), and high-density lipoprotein cholesterol (HDL-C; WMD: 1.57 mg/dL, 95% CI: -0.95-4.10, p = .22). However, subgroup analyses showed that serum LDL-C levels were significantly reduced in trials administered > 50 g/d almond. The data suggest that consumption of almond could not improve lipid profile in patients with T2DM.

Context: The evidence on potential cross-talk of vitamin D and insulin in the regulation of cardiac metabolism is very scanty.

Objective: Cholecalciferol was administered to male Wistar rats for six weeks to study its effects on cardiac glucose metabolism regulation.

Materials and methods: An expression, phosphorylation and/or subcellular localisation of insulin signalling molecules, glucose transport and metabolism key proteins were studied.

Results: Circulating non-esterified fatty acids (NEFA) level was lower after cholecalciferol administration. Cholecalciferol decreased cardiac insulin receptor substrate 1 Ser³⁰⁷ phosphorylation, while insulin-stimulated Akt Thr³⁰⁸ phosphorylation was increased. Cardiac 6-phosphofructo-2-kinase protein, hexokinase 2 mRNA level and insulin-stimulated glycogen synthase kinase 3β Ser⁹ phosphorylation were also increased. Finally, FOXO1 transcription factor cytosolic level was reduced.

Conclusion: Vitamin D-related improvement of insulin signalling and insulin regulation of glucose metabolism in the rat heart is accompanied by the decrease of blood NEFA level and dysregulation of cardiac FOXO1 signalling.

Background: The aim of this study was to compare the sex-dependent intergenerational effects of insulin, glibenclamide, and metformin on glucose and lipid metabolism in the offspring born to GDM mice.

Methods: The murine GDM was induced by high fat diet. The offspring were grouped based on the treatments in maternal mice. ITT and GTT were performed at 4th and 8th weeks of age, respectively. Serum levels of TC, TG, HDL-C, and LDL-C plus hepatic levels of TG and TC, were respectively determined by enzymatic kits. Western blotting was conducted to detect related proteins in the livers from offspring.

Results: The dyslipidaemia, hepatic lipid abnormality, and insulin insensitivity caused by GDM were persistently normalised in male adult offspring by the respective therapies of insulin, glibenclamide, and metformin during maternal pregnancy. Specifically, the decreases in plasma TC, TG, and LDL-C levels (29%, 37.8%, and 57.7%, respectively, p ˂ .05) and in hepatic lipid contents (TC 31.3% and TG 39.2%, p ˂ .05), the increases in hepatic phosphorylation levels of AKT, CPT1A, PPAR-α, and PPAR-γ (57.1%, 91.7%, 68%, and 173.3%, respectively, p ˂ .05) and the inhibition of G6Pase, PEPCK, and HMGCS1 (35.7%, 68.8%, and 77.3% respectively, p ˂ .05) were still observed in the male offspring born to treated GDM mice from 4th to 8th week of age. Unexpectedly, the aforementioned parameters in female progenies in different groups were not significantly changed compared with controls.

Conclusions: Respective treatments in GDM mice during pregnancy with insulin, glibenclamide, and metformin have the long-term persistent effects in male offspring, while female progenies born to untreated dams showed an autonomous inhibition of intergenerational relay of glucose and lipid dysregulation. Our current findings may imply a sex-dependent strategy of medical care for GDM mothers and their offspring.NoveltiesRespective interventions of insulin, glibenclamide, and metformin on dams exerted the persisted effects on male progenies.Therapies of three drugs on dams had the similarly improved effects in offspring.Female offspring autonomously corrected their dysregulated glucose-lipid metabolism caused by gestational diabetes mellitus (GDM) in dams.

Diabetic retinopathy (DR) is the main cause of adult insomnia, which causes certain social and economic pressure. This research was to investigate the role and regulatory mechanisms of MALAT1, miR-378a-3p and PDE6g in retinal microvascular endothelial cells (RMECs) under high glucose (HG). MALAT1, Mir-378a-3p and PDE6G expressions level were detected by qRT-PCR and Western blot. The proliferation, Bax and Bcl-2 protein expression of RMECs were detected by CCK-8 and western blot. The target relationships of MALAT1, miR-378a-3p and PDE6G were determined by bioinformatics analysis, dual-luciferase reporter gene, RIP and RNA pull-down assay. HG enhanced the expression of MALAT1 and PDE6G, and inhibited the expression of miR-378a-3p. Overexpression of MALAT1 promotes the proliferation of RMECs and inhibits apoptosis under HG condition. MALAT1 competitively adsorbed miR-378a-3p, which targeted PDE6G. Data reveal that MALAT1/miR-378a-3p/PDE6G signal axis restrain the apoptosis of RMECs under HG. This finding may help to delay the development of DR.