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.

The effectiveness and safety of recombinant human growth hormone combined with alginate dressing in the treatment of diabetic foot ulcer: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic foot ulcer (DFU) is one of the serious complications of diabetes. It is the result of a joint effect of lower extremities vascular lesions, neuropathy, and infection, which require amputation and even threaten the life of the patient. At present, the conventional treatment for DFU includes infection control, wound care, wound reduction, reduction of foot pressure, use of dressings that are beneficial to wound surface healing, etc, but the effectiveness is not satisfactory. Recombinant human growth hormone and alginate dressing have been used in clinical, but there is lack of the relevant evidence of its effectiveness and safety, so this study evaluates the clinical effectiveness and safety of recombinant human growth hormone combined with alginate dressing in the treatment of DFU by systematic evaluation, the purpose is to provide a theoretical basis for the treatment of diabetic foot ulcer. METHODS: This study mainly retrieves the randomized controlled trial of recombinant human growth hormone combined alginate dressing in the treatment of DFU in 7 electronic databases, such as PubMed, EMbase, Cochrane Library, SinoMed, CNKI, WANGFANG database, and VIP database. All the retrieval dates of database are from the establishment of the database until May 31, 2020. At the same time, searching the related degree papers, conference papers, and other gray literature by manual. The original literature data are independently screened and extracted by 2 researchers on the basis of inclusion and exclusion criteria and literature information sheets, and cross-checked and resolved through group discussions and consultations when there are differences of the opinion. Assessing the methodological quality of inclusion in the study based on the "Bias Risk Assessment Form" of the Cochrane Collaboration Network. Using the software of RevMan 5.3.3 and STATA 13.0 for statistical analysis. RESULTS: This study compares the main and secondary outcome indicators by systematic evaluation and it will provide strong evidence of recombinant human growth hormone combined alginate dressing in the treatment of DFU. ETHICS AND DISSEMINATION: All data in this study are obtained through the web database and do not involve humans, so ethical approval is not suitable for this study. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/W6P24. CONCLUSION: This study will give positive conclusions about the effectiveness and safety of recombinant human growth hormone combined alginate dressing in the treatment of DFU.

Initial empirical treatment based on clinical feature of chronic cough.

BACKGROUND: An empirical therapy based on the clinical characteristics of cough had not been reported. We evaluated this strategy of empirical therapy on chronic cough. METHODS: Patients with chronic cough were initially diagnosed with corticosteroid-responsive cough (CRC), postnasal drip syndrome (PNDS) and gastroesophageal reflux-related cough (GERC) based on their medical history and clinical presentation, and received a sequential three-step empirical therapy. A successful response was required for final diagnosis. RESULTS: A total of 96 patients were recruited with a median duration of cough for 4 months (range, 2-100). The primary diagnosis based on history and clinical presentation was CRC in 53 patients (55.2%), PNDS in 36 (37.5%) and GERC in 7 (7.3%). Cough improved in 60 patients (62.5%) at the first step with mean time of 6.2 ± 3.3 days. Three-step empirical therapy was beneficial in 78 of 96 (81.2%) patients at last. The final spectrum and frequency of causes of cough based on therapeutic response were as follows: CRC (46.7%), PNDS (27.5%) and GERC (10.8%). Eighteen cases (18.8%) were not responsive to empirical treatment, seven of whom were identified as other causes by diagnostic tests. CONCLUSIONS: The empirical therapy aimed at primary diagnosis on the basis of history and clinical characteristics is a more targeted approach, and leads to improvement of chronic cough more quickly in most patients. CRC is the most common cause of chronic cough.

Leonurine (SCM-198) attenuates myocardial fibrotic response via inhibition of NADPH oxidase 4.

In our previous studies, we have reported that leonurine, a plant phenolic alkaloid in Herba leonuri, exerted cardioprotective properties in a number of preclinical experiments. Herein, we investigated the roles and the possible mechanisms of leonurine for reducing fibrotic responses in angiotensin II (Ang II)-stimulated primary neonatal rat cardiac fibroblasts and post-myocardial infarction (MI) rats. In in vitro experiments performed in neonatal rat cardiac fibroblasts, leonurine (10-20 µM) pretreatment attenuated Ang II-induced activation of extracellular signal-regulated kinase 1/2, production of intracellular reactive oxygen species (ROS), expression and activity of matrix metalloproteinase (MMP)-2/9, and expression of α-smooth muscle actin and types I and III collagen. A small interfering RNA-mediated knockdown strategy for NADPH oxidase 4 (Nox4) revealed that Nox4 was required for Ang II-induced activation of cardiac fibroblasts. In vivo studies using a post-MI model in rats indicated that administration of leonurine inhibited myocardial fibrosis while reducing cardiac Nox4 expression, ROS production, NF-κB activation, and plasma MMP-2 activity. In conclusion, our results provide the first evidence that leonurine could prevent cardiac fibrosis and the activation of cardiac fibroblasts partly through modulation of a Nox4-ROS pathway.

Inhibition of NADPH oxidase 4-related signaling by sodium hydrosulfide attenuates myocardial fibrotic response.

BACKGROUND: Myocardial fibrosis plays a pivotal role in the development of heart failure. Hydrogen sulfide (H2S) is an endogenous gasotransmitter with potent cardioprotective properties; however, whether H2S is involved in fibrotic process remains unknown. This study aimed to explore the role of H2S in the process of cardiac fibrosis and the underlying mechanisms. METHODS: Myocardial infarction (MI) was established in rats by ligation of coronary artery. Activation of rat neonatal cardiac fibroblasts was induced by angiotensin II (Ang II). Fibrotic responses in ischemic myocardium and in Ang II-stimulated cardiac fibroblasts were examined. The effects of sodium hydrosulfide (NaHS, an exogenous H2S donor) on NADPH oxidase 4 (Nox4), reactive oxygen species (ROS) production, extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, heme oxygenase-1 (HO-1), and cystathionine γ-lyase (CSE) were tested to elucidate the protective mechanisms of H2S on fibrotic response. RESULTS: NaHS treatment inhibited Ang II-induced expression of α-smooth muscle actin, connective tissue growth factor (CTGF), and type I collagen and upregulated expression of HO-1 in cardiac fibroblasts. Ang II-induced Nox4 expression in cardiac fibroblasts was quenched by NaHS and this was associated with a decreased ROS production and reduced ERK1/2 phosphorylation and CTGF expression. In vivo studies using MI model indicated that NaHS administration attenuated Nox4 expression and fibrotic response. Moreover, NaHS therapy also prevented cardiac inflammatory response accompanied by increases in HO-1 and CSE expression. CONCLUSIONS: The beneficial effect of H2S, at least in part, was associated with a decrease of Nox4-ROS-ERK1/2 signaling axis and an increase in HO-1 expression.

Synthesis, complexation, and fluorescence behavior of 3,4-dimethylthieno[2,3-b]thiophene carrying two monoaza-15-crown-5 ether groups.

A novel fluoroionophore 1 based on 3,4-dimethylthieno[2,3-b]thiophene bearing two monoaza-15-crown-5 ethers at 3- and 4-positions was prepared. UV-vis and fluorescence responses of compound 1 upon the addition of alkali and alkaline earth metal cations were evaluated in acetonitrile solution. Receptor 1 showed unique response for Ba(2+) due to the formation of an intramolecular sandwich complex.

Thrombopoietin protects against doxorubicin-induced cardiomyopathy, improves cardiac function, and reversely alters specific signalling networks.

AIMS: We investigated the therapeutic efficacy of thrombopoietin (TPO) in acute and chronic rat models of heart damage and explored the mechanisms in terms of genome-wide transcriptional changes, phosphorylation signals, and bone marrow endothelial progenitor cell (EPC) levels. METHODS AND RESULTS: Cardiac damage was induced in rat models of (i) acute-doxorubicin (DOX) treatment: single high-dose DOX, four doses TPO, followed up for 5 days; and (ii) chronic-DOX treatment: one low-dose DOX and three doses TPO weekly for 6 weeks, followed up for 11 weeks. Our results demonstrated that TPO treatment led to significant improvements of fractional shortening, cardiac output, and morphologic parameters in both models. In the acute-DOX model, microarray and network analyses showed that DOX damage was associated with changes in a large cohort of gene expressions, of which many were inversely regulated by TPO, including modulators of signal transduction, ion transport, anti-apoptosis, protein kinase B/ p42/p44 extracellular signal-regulated kinase (AKT/ERK) pathways, cell division, and contractile protein/matrix remodelling. Many of these regulations also occurred in chronic-DOX animals, in which TPO treatment reduced morphological damage and cardiomyopathy score, and increased AKT phosphorylation of heart tissues. Thrombopoietin also increased EPC colonies in their bone marrow. CONCLUSION: Our overall data suggest that TPO promotes cardiac protection from acute- and chronic-DOX insults, possibly mediated by multi-factorial mechanisms including AKT- and ERK-associated restoration of regulatory gene activities critical for normal heart function.

Dexrazoxane protects against doxorubicin-induced cardiomyopathy: upregulation of Akt and Erk phosphorylation in a rat model.

PURPOSE: Dexrazoxane (DZR), a clinically approved cation chelator, is effective in reducing doxorubicin (DOX)-induced heart damage, yet its cardioprotective mechanism is not fully understood. We aimed to investigate the effects of DZR on the activation of Akt and Erk 1/2 signals in a rat model of DOX-induced cardiomyopathy. METHODS: Male Sprague-Dawley rats received weekly DOX injection (2.5 mg/kg) for 6 weeks, with or without DZR pretreatment at a dose ratio of 20:1. The ventricular functions of these animals were monitored at week 6, 9 and 11 by echocardiography. At week 11, their heart morphology was studied by light and electron microscopy. Phosphorylation of Akt and Erk in heart tissues was measured by Western blot analysis. RESULTS: DOX caused myocardial damage with compromised left ventricular function, increased myocardium injury and reduced phosphorylation of Akt and Erk. DZR exerted a significant cardioprotective effect in terms of improved fractional shortening, cardiac output and cardiomyopathy score at one or more time points. We also provided the first evidence that dexarazoxane-treated animals had increased levels of Akt and Erk activation, whilst total Akt and Erk remained unchanged. CONCLUSIONS: Our results showed that the cardioprotective effect of dexarazoxane has been sustained beyond the treatment period. The data also suggested that activation of the Akt and Erk signaling pathways was regulated in the course of DOX-induced cardiomyopathy and protection by DZR.