Homocysteine level and gestational diabetes mellitus: a systematic review and meta-analysis.

AIMS: It is reported that elevated homocysteine (Hcy) level represents an independent risk factor for gestational diabetes mellitus (GDM). However, the relationship between Hcy level and GDM remains controversial. Our study aimed to systematically review available literature linking Hcy to GDM for a comprehensive understanding of the relationship between circulating Hcy level and GDM in humans. METHODS: PubMed, The Cochrane Library, and Web of Science were searched for studies published up to January 2021. Manual searches of references of the relevant studies were also conducted. Standard mean difference (SMD) with 95% confidence interval (95%CI) were calculated to evaluate the relationship between Hcy level and GDM using the Review Manager 5.3 and Stata 12.0. RESULTS: Of 106 references reviewed, 12 studies with a total of 712 GDM patients contributed to the present meta-analysis. Hcy level was significantly elevated in women with GDM compared with those without GDM (SMD = 0.55; 95% CI: 0.25-0.85, p = .0003). In the subgroup meta-analyses, this evidence was more consistent among women with Hcy sampling during the second trimester (SMD = 0.76, 95% CI: 0.34-1.18, p = .0004) and with average age ≥30 years (SMD = 0.69, 95% CI: 0.25-1.12, p = .002). CONCLUSION: The evidence indicated that the level of circulating Hcy was significantly elevated among women with GDM compared with those with normal glucose tolerance, especially with mean age ≥30 years and in the second trimester.

Visfatin level and gestational diabetes mellitus: a systematic review and meta-analysis.

It is reported that elevated visfatin level is associated with gestational diabetes mellitus (GDM). However, the relationship between visfatin level and GDM remains controversial. The aim of our study was to systematically review available literature linking visfatin to GDM for a comprehensive understanding of the relationship between circulating visfatin level and GDM in human. PubMed, The Cochrane Library and Web of Science were searched for studies published up to July 2020. Standard mean difference with 95% confidence interval was calculated to evaluate the relationship between visfatin level and GDM using the Review Manager 5.3 and Stata 12.0. The evidence indicated that no significant difference was observed in the level of circulating visfatin between the women with GDM and normal glucose tolerance, suggesting circulating visfatin level is not independently related to GDM. Nevertheless, visfatin is involved in the development of GDM in obese women.

Sonic hedgehog signaling regulates hypoxia/reoxygenation-induced H9C2 myocardial cell apoptosis.

The sonic hedgehog (Shh) signaling pathway has been reported to protect cells against hypoxia/reoxygenation (H/R) injury; however, the role of Shh and relevant molecular mechanisms remain unclear. In the present study, the rat cardiomyoblast cell line H9C2 was subjected to hypoxia and serum-starvation for 4 h. Cells were subsequently reoxygenated using 95% O2 and 5% CO2. Reverse transcription-quantitative polymerase chain reaction was performed to quantify the expression of Shh mRNA, while cell apoptosis was assessed using flow cytometry. Caspase-3 activity and p53 expression were measured by western blotting and an MTT assay was subsequently used to assess cell viability. In addition, reactive oxygen species levels were measured using dichlorofluorescein and H/R-induced changes in the activation of superoxide dismutase, catalase, phosphorylated-endothelial nitric oxide synthase, phosphorylated-protein kinase B (Akt) and mammalian target of rapamycin activation were assessed using western blotting. H/R treatment decreased the cell viability of H9C2 cells, but activated endogenous Shh signaling. The activation of Shh signaling protected H9C2 myocardial cells from H/R-induced apoptosis and restored cell viability. In the present study, Shh signaling was demonstrated to serve a protective role against H/R by activating the phosphoinositol 3-kinase (PI3K)/Akt pathway and promoting the expression of anti-oxidant enzymes to ameliorate oxidative stress. In summary, Shh signaling attenuated H/R-induced apoptosis through via the PI3K/Akt pathway.

Diosgenin Protects Rats from Myocardial Inflammatory Injury Induced by Ischemia-Reperfusion.

BACKGROUND Diosgenin, a phytosteroid sapogenin, has anti-inflammatory properties shown to reduce myocardial ischemia-reperfusion injury (MIRI). However, the specific mechanism by which this is achieved is not clear. This study investigated the protective effects of diosgenin on myocardial ischemia/reperfusion (I/R) and the potential anti-inflammatory mechanisms. MATERIAL AND METHODS Healthy adult male SD rats, body weight (b.w.) 250-280 g, were used to model ischemia-reperfusion injury (IRI) and were administered diosgenin (50 mg/kg and 100 mg/kg b.w.) intragastrically for 4 consecutive weeks before surgery. The left anterior descending artery (LAD) was ligated to induce myocardial ischemia for 30 min and reperfusion for 30 min, 60 min, and 120 min while relevant indicators were detected. RESULTS Both 50 mg and 100 mg diosgenin oral administration increased left ventricular developed pressure (LVDP) and maximum changing rate of ventricular pressure (±dp/dtmax), decreased left ventricular end-diastolic pressure (LVEDP), and myocardial enzyme markers. TTC staining suggested that diosgenin reduced myocardial infarct size in the rat model. Pathological results showed that myocardial ischemia and inflammation were alleviated by diosgenin. In addition, the increased expression of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß) in serum, and myeloperoxidase (MPO) in myocardium were significantly suppressed by diosgenin administration. Diosgenin further inhibited the phosphorylation of transcription factor NF-κB and modulated the expression of downstream inflammatory cytokines by regulating the activation of p38-MAPK and JNK pathways. CONCLUSIONS Results demonstrate diosgenin plays an anti-inflammatory role in the protection of MIRI through regulation of p38-MAPK and JNK pathways and phosphorylation of NF-κB.

Glucagon-like peptide-1 protects against cardiac microvascular endothelial cells injured by high glucose.

OBJECTIVE: To investigate the protective effect of glucagon-like peptid-1 (GLP-1) against cardiac microvascular endothelial cell (CMECs) injured by high glucose. METHODS: CMECs were isolated and cultured. Superoxide assay kit and dihydroethidine (DHE) staining were used to assess oxidative stress. TUNEL staining and caspase 3 expression were used to assess the apoptosis of CMECs. H89 was used to inhibit cAMP/PKA pathway; fasudil was used to inhibit Rho/ROCK pathway. The protein expressions of Rho, ROCK were examined by Western blot analysis. RESULTS: High glucose increased the production of ROS, the activity of NADPH, the apoptosis rate and the expression level of Rho/ROCK in CMECs, while GLP-1 decreased high glucose-induced ROS production, the NADPH activity and the apoptosis rate and the expression level of Rho/ROCK in CMECs, the difference were statistically significant (P<0.05). CONCLUSIONS: GLP-1 could protect the cardiac microvessels against oxidative stress and apoptosis. The protective effects of GLP-1 are dependent on downstream inhibition of Rho through a cAMP/PKA-dependent manner, resulting in a subsequent decrease in the expression of NADPH oxidase.

The effects of subclinical hypothyroidism on serum lipid level and TLR4 expression of monocyte in peripheral blood of rats.

OBJECTIVE: To observe effect of subclinical hypothyroidism (SCH) on serum lipid level and expression of toll-like receptor 4 (TLR4) in rats' peripheral blood mononuclear cells (PBMC). METHODS: Fifty Wistar female rats were divided into three groups: normal control (NC group; n=10), sham group (n=10), and L-T-4 (L-thyroxine) group (n=30, with thyroidectomy, fed with rich-calcium water after operation. 5 weeks later, abdominal subcutaneous injection of L-T-4: 0.95 µg/100g/d). 8 weeks later, the rats were killed then the peripheral blood was collected to determine the levels of serum thyroid-stimulating hormone (TSH), total thyroid hormone (TT4), total cholesterol (TC) and low density lipoprotein cholesterin (LDL-C). Rats in L-T-4 group were divided into normal lipid (NL) group) and high lipid (HL) group) according to lipid value of NC group. Monocytes were separated from blood to determine TLR4 expression by flow cytometry. RESULTS: In NL and HL groups TSH were higher than in NC and Sham groups (p<0.05). TT4 have no significant differences (p>0.05). TLR4, TLR4 mRNA, NF-κB (p65) were increased (p<0.05). TNF-α, IL-6 and IL-1ß were higher than in NC and sham groups (p<0.01). There were no significant differences of TLR4, TLR4 mRNA, NF-κB (p65), TNF-α, IL-6 and IL-1ß expression between NL and HL groups (p>0.05). CONCLUSION: TLR4, TLR4 mRNA, NF-κB (p65) of PBMC and TNF-α, IL-6, IL-1ß expression in serum were all increased in SCH rats, which was not related to serum dyslipidemia.

Ginkgo biloba extract reducing myocardium cells apoptosis by regulating apoptotic related proteins expression in myocardium tissues.

The Bax, cyt-c and caspase-3 proteins play an important role in regulating the myocardial apoptosis. Although very little is known about the specific signal pathways modulated by Ginkgo biloba extract (GBE), it seems advisable to suppose that GBE-induced antiapoptotic effect might be attributed to the regulation of the expression of these proteins. Our aim was to investigate whether GBE could attenuate ischemia/reperfusion-induced apoptosis in cardiac myocytes and its potential mechanisms. In the myocardium ischemia reperfusion (IR) rat model, treatment of GBE (400 mg/kg) significantly decreased the cardiomyocyte cell apoptosis and myocardium infarction. Immunohistochemical analysis showed that GBE significantly inhibited I/R-induced increase of myocardial Bax, caspase-3, and cyt-c proteins expression. Western blot analysis confirmed results of immunohistochemical analysis. It is most likely that multiple pathways are involved in IR-induced apoptosis in rat myocardium cells. Therefore, these results demonstrate that GBE exhibits significant protective effect against myocardial I/R injury in rat heart, which is related to down-regulate Bax, cyt-c and caspase-3. Bcl-2 overexpression might prevent IR-induced apoptosis by inhibiting cytochrome c release from the mitochondria and block activation of caspase-3.

A new hepoprotective saponin from Semen Celosia cristatae.

A new triterpenoid saponin, named semenoside A (1), was isolated from Semen Celosia cristatae. Its structure was elucidated on the basis of 1D, 2D NMR, HR-FAB-MS and ESI-MS techniques, and physicochemical properties. The hepatoprotective activity of semenoside A with an oral dose of 1.0, 2.0 and 4.0mg/kg, respectively, were investigated by carbon tetrachloride (CCl(4))-induced hepatotoxicity in mice. The results indicated that it had significant hepatoprotective effects (p < 0.01).