Objective To systematically review the efficacy and safety of different SGLT2 inhibitors in the treatment of heart failure. Methods The Cochrane Library, Web of Science, PubMed and EMbase databases were searched for randomized controlled trials on the efficacy and safety of SGLT2 inhibitors in patients with heart failure from inception to July 2, 2021. Two researchers independently screened literature, extracted data and evaluated the risk of bias of the included studies. Network meta-analysis was then performed using Stata 16.0 software. Results A total of 16 randomized controlled trials, including 15 312 patients, involving 5 interventions, namely dapagliflozin, empagliflozin, canagliflozin, sotagliflozin and ertugliflozin were included. Results of network meta-analysis showed that there was no significant difference in the compound outcome of hospitalization for heart failure or cardiovascular death, hospitalization for heart failure, all-cause mortality, risk of cardiovascular mortality and serious adverse reactions among patients with heart failure among 5 different SGLT2 inhibitors (P>0.05). Compared with placebo, both selective and non-selective SGLT2 inhibitors improved the risk of hospitalization for heart failure, hospitalization for heart failure, or compound cardiovascular mortality (P<0.05), while only selective SGLT2 inhibitors improved the risk of cardiovascular mortality, all-cause mortality, and serious adverse events (P<0.05). However, there was no significant difference between them (P>0.05). The area under the cumulative ordering probability curve of selective and non-selective SGLT2 inhibitors ranked first and second, except for the combined outcome of heart failure or cardiovascular death. Conclusion The current evidence indicates that there is no significant difference in the efficacy and safety of the 5 different SGLT2 inhibitors in the treatment of heart failure, and there is no significant difference between selective SGLT2 inhibitors and non-selective SGLT2 inhibitors. Due to the limited quantity and quality of included studies, more high-quality studies are needed to verify the above conclusion.
ObjectiveTo study the effects of Ghrelin for glucose metabolism and insulin sensitivity of L6 rat myoblasts in palmitic acid induced, and to explore its possible mechanisms. MethodsThe L6 rat myoblasts were cultured until differentiation, then using palmitic acid(0.3 mmol/L) for 16 hours. The experimental group was treated with different doses of Ghrelin(1, 10, and 100 nmol/L) for 8 hours, then the glucose uptake was detected by using glucose oxidase peroxidase method(GOD-POD), the cell membrane glucose transporter 4(GLUT-4) protein staining was observated under confocal microscopy, and the expressions of total protein kinase B(Akt), phosphorylated protein kinase B(pAkt), total glycogen synthase kinase-3β(GSK-3β), and phosphorylated glycogen synthase kinase-3β(pGSK-3β) were detected by using immunoblotting(Western blot). ResultsGhrelin enhanced the glucose uptake of L6 rat myoblasts with insulin resistance, the cell membrane Glut-4 stain was deepen, the expressions of pAkt and pGSK-3βprotein increased, and this effect could be PI3K blocker(LY294002) eliminated. ConclusionGhrelin promotes the glucose uptake of L6 rat myoblasts through PI3K/Akt/GSK-3βsignaling pathway, so as to improve the sensitivity of insulin in L6 rats muscle cells.
Sodium-glucose cotransporter (SGLT) -2 inhibitors is a new type of oral sugar-lowering drug. Instead of relying on insulin, it lowers blood sugar by inhibiting the reabsorption of near-curvy tube glucose, which is drained from the urine. SGLT-2 inhibitors not only have a sugar-lowering effect, but also benefit significantly in cardiovascular disease, and this drug has the advantages of permeable diuretic, reducing capacity load, and improving ventricular remodeling. SGLT-2 inhibitors can improve the diastolic function of patients with heart failure with preserved ejection fraction (HFpEF) and reduce the risk of adverse cardiovascular events. SGLT-2 inhibitors can benefit patients with HFpEF. Therefore, this article will discuss the progress of SGLT-2 inhibitors in HFpEF.
Objective To observe the different effect such as high concentration of glucose and high concentration of insulin on GLUT1 of Rabbit Retinal Muuml;ller Cell in vitro. Methods Rabbit retinal Muuml;ller cells were cultured in vitro with suspended constitution，which were divided as the following groups: common control group，high glucose group，insulin group，high glucose combined insulin group. Laser confocal microscope combined with immunocytochemical and fluorescence staining method to quantitatively analyze the expression condition of GLUT1. Results The expression of GLUT1 has been enhanced obviously by high glucose and high insulin，which locates mainly in the cytoplasm that near to the nucleus. Conclusion Rabbit retinal Muuml;ller cells can express GLUT1，and the expression of GLUT1 can be reinforced by high glucose and high insulin. （Chin J Ocul Fundus Dis，2008，24：265-267）
OBJECTIVE:To investigate the transporting function of subretinal fluid in retinal pigment epithelium(RPE) of experimental retinal detachment (RD). METHODS: Twenty-seven pigmented rabbits with one eye as retinal detachment model and the other eye as control were divided into 4 groups ,ic. 7 rabbits in each group at random. The Na十-K+-ATPase activity in RPE-choroidal tissue at the detached region in both experimental and control eyes was determined at the lst,2nd,3rd and 4th week after retinal detachment,and also the ultrastructure of the RPE-choroidal tissues observed. RESULTS:The activity of Na十-K+-ATPase of experimental eyesE[(2.16士1.26)/mu;mol(mgmiddot;h)]was significantly lower than that of the controis[(4.84plusmn;1.59)mu;mol/(mgmiddot;h)]. The degree of decreasing activity was relieving along with increasing of the course of RD. The inward pinocytosis in RPE cells under electron-microscope was found from the 2nd week samples afterwards and becoming obvious along with increasing of the disease course. CONCLUSIONS:The outward transporting function of RPE was increased after RD,it became decreased along with increasing of the course df RD and the inward transporting function then developed.
Objective To investigate the clinical significance of the three iodide transporters in thyroid diseases. Methods Literatures about the Na+/I- symporter (NIS), pendrin and human apical iodide transporter (hAIT) in recent years were reviewed and their expressions in different thyroid diseases were also analyzed. Results NIS proteins express at the basolateral membrane of thyrocytes in normal thyroid tissue, while pendrin and hAIT proteins are limited to the apical membrane of thyrocytes lining in the follicular lumen. In the tissues of thyroid carcinomas, it was found that the NIS proteins expressed in the cytoplasm and their expressions decreased; The mutation of NIS gene may be one of the main causes of congenital hypothyroidism. The expression of prendrin protein may be related to the function of follicles: its expression level increased significantly both in Graves diseases and toxic adenomas, but significantly decreased in differentiated thyroid carcinoma. However, the correlation between the decrease and the degrees of differentiation of carcinoma cell line are still disputable. The expression of hAIT protein does not significantly altered in hyperfunctioning tissues. It only slightly decreased occasionally in hypofunctioning adenomas, but it decreased significantly in thyroid carcinomas. Conclusion The abnormal expressions of the three iodide transporters may be related closely with the type of thyroid diseases. However, their pathogenic mechanisms and the causes of their abnormal expression are still unknown, which need to be studied further.
Objective To observe the effects of bevacizumab on aquaporin 4 (AQP4) expression in human retinal Muuml;ller cells in vitro under hypoxia. To explored the mechanism of treating retinal edema with bevacizumab. Methods Human Muuml;ller cells were cultured using the enzymatic digestion method. Transmission electron microscopic analysis and immunofluorescence staining identified Muuml;ller cells. With semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), the expression of AQP4 mRNA and vascular endothelial growth factor （VEGF） mRNA in Muuml;ller cells cultured under different concentration of COCl2 for different hours were observed. The expression of AQP4 mRNA in Muuml;ller cells cultured using CoCl2 precultured with 200 mu;g/ml bevacizumab was measured. Results More than 95% of primary cells showed positive reaction to glial fibrillary acidic protein, glutamine synthetase, vimentin and alpha;-smooth muscle actin with immunofluorescence staining. Characteristic 8-10 nm intracellular filaments could be seen in the cytoplasm viewed with transmission electron microscopy. The results using RT-PCR showed that CoCl2 increased the AQP4 and VEGF mRNA expression in Muuml;ller cells in a dose and time dependent manner (r=0.952, 0.954;P＜0.05). The expression of AQP4 mRNA in Muuml;ller cells was increased by VEGF (F=12.43,P＜0.05). The expression of AQP4 mRNA was significantly decreased by bevacizumab (F=2 370.37，P＜0.05). Conclusion Bevacizumab can down-regulate the expression of AQP4 mRNA in human Muuml;ller cells under hypoxic conditions partially by VEGF path, which may be a mechanism for treating retinal edema with bevacizumab.