Impact of DPP-4 inhibitors on plasma levels of BNP and NT-pro-BNP in type 2 diabetes mellitus.

BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4i) decrease glucose levels by regulating incretin peptides in type 2 diabetes mellitus (T2DM). This study aimed to determine the modulatory effect of DPP-4i on brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in patients with T2DM. METHODS: PubMed, Embase and the Cochrane Library were systematically searched to identify randomized controlled trials (RCTs) evaluating the impact of DPP-4i on BNP or NT-pro-BNP. A fixed- or random-effects model was used for quantitative analysis, according to the heterogeneity. Sensitivity analysis and publication bias were performed using standard methods. RESULTS: Nine trials with 3056 patients with T2DM were included. Meta-analysis revealed that DPP-4i did not significantly modulate the BNP (0.21 pg/mL, 95% CI - 2.36-2.79) or NT-pro-BNP level (- 7.34 pg/mL, 95% CI - 24.27-9.59). DPP-4i demonstrated no stronger effect on modulating BNP (5.17 pg/mL, 95% CI - 7.48-17.82) or NT-pro-BNP (- 9.95 pg/mL, 95% CI - 44.61-24.71) than active comparators. Pooled analysis was robust and stable after sensitivity analysis. CONCLUSIONS: DPP-4i exhibits no significant effect on modulating BNP or NT-pro-BNP and shows no stronger effect than traditional antidiabetic agents in T2DM.

TIMELESS inhibits breast cancer cell invasion and metastasis by down-regulating the expression of MMP9.

Breast cancer is the first killer leading to female death, and tumor metastasis is one of the important factors leading to the death of patients, but the specific mechanism of breast cancer metastasis is not very clear at present. Our study showed that overexpression of TIMELESS could significantly inhibit the invasion and metastasis of breast cancer cells ZR-75-30 and the assembly of F-actin protein. On the contrary, knockdown of TIMELESS promoted the invasion and metastasis of breast cancer cells. Further study revealed that TIMELESS overexpression decreased the mRNA and protein levels of MMP9. Furthermore, TIMELESS could interact with p65, leading to repress the association of p65 and its acetyltransferase CBP and down-regulating the acetylation level of p65, which inhibited the activation of NF-κB signal pathway. In conclusion, our research showed that TIMELESS may repress the invasion and metastasis of breast cancer cells via inhibiting the acetylation of p65, inhibiting the activation of NF-κB, thus down-regulating the expression of MMP9, and then inhibiting the invasion and metastasis of breast cancer cells.

Associations between TNFSF4 gene polymorphisms (rs2205960 G > A, rs704840 T > G and rs844648 G > A) and susceptibility to autoimmune diseases in Asians: a meta-analysis.

BACKGROUND: Tumor necrosis factor superfamily member 4 (TNFSF4) has significant role in modulating autoimmune diseases (ADs) and single nucleotide polymorphism (SNP) is also related with the susceptibility to some diseases. So a meta-analysis aimed at systematically assessing the associations between TNFSF4 polymorphisms (rs2205960 G > A, rs704840 T > G and rs844648 G > A) and ADs risk was performed in Asians. METHODS: Total 14 eligible articles published before March 2019 involving 35 studies, of which 21 studies (16,109 cases and 26,378 controls) for rs2205960 G > A, 8 studies (2,424 cases and 3,692 controls) for rs704840 T > G, and 6 studies (3,839 cases and 5,867 controls) for rs844648 G > A were included. Effects of the three respective polymorphisms on the susceptibility to ADs were estimated by pooling the odds ratios (ORs) with their corresponding 95% confidence interval (95% CI) in allelic, dominant, recessive, heterozygous and homozygous models. RESULTS: The overall analysis revealed that all the rs2205960 G > A, rs704840 T > G and rs844648 G > A polymorphisms could increase the risk of ADs in allelic, dominant, recessive, heterozygous and homozygous models. Furthermore, subgroup analysis showed that both rs2205960 G > A and rs704840 T > G were significantly associated with the susceptibility to systemic lupus erythematosus (SLE). What's more, statistically significant association between rs2205960 G > A polymorphism and primary Sjögren's syndrome (pSS) susceptibility was also observed in allelic, dominant and heterozygous models. CONCLUSIONS: This current meta-analysis suggested that all of the three TNFSF4 polymorphisms may be associated with ADs susceptibility in Asians.

Manganese-catalysed divergent silylation of alkenes.

Transition-metal-catalysed, redox-neutral dehydrosilylation of alkenes is a long-standing challenge in organic synthesis, with current methods suffering from low selectivity and narrow scope. In this study, we report a general and simple method for the manganese-catalysed dehydrosilylation and hydrosilylation of alkenes, with Mn2(CO)10 as a catalyst precursor, by using a ligand-tuned metalloradical reactivity strategy. This enables versatility and controllable selectivity with a 1:1 ratio of alkenes and silanes, and the synthetic robustness and practicality of this method are demonstrated using complex alkenes and light olefins. The selectivity of the reaction has been studied using density functional theory calculations, showing the use of an iPrPNP ligand to favour dehydrosilylation, while a JackiePhos ligand favours hydrosilylation. The reaction is redox-neutral and atom-economical, exhibits a broad substrate scope and excellent functional group tolerance, and is suitable for various synthetic applications on a gram scale.

Association of polymorphisms of CYP11B2 gene -344C/T and ACE gene I/D with antihypertensive response to angiotensin receptor blockers in Chinese with hypertension.

The aim of this study was to determine whether the polymorphism of aldosterone synthase (CYP11B2) -344C/T and angiotensin-converting enzyme (ACE) insertion/deletion (I/D) were associated with the response of blood pressure (BP) to telmisartan treatment. After a two-week single-blind placebo run-in period, 148 patients with mild-to-moderate primary hypertension received monotherapy of telmisartan with 80 mg/day and then were followed up for eight weeks. Polymorphisms of CYP11B2 -344C/T and ACE I/D gene were determined through polymerase chain reaction-restriction fragment polymorphism analysis. The relationship between these polymorphisms and changes in BP was monitored and evaluated after eight weeks of treatment. With respect tothe polymorphism of CYP11B2 -344C/T, the reduction in diastolic BP was significantly greater in patients carrying the C allele (CC+CT) compared with those carrying the TT genotype. There was no significant differences between ACE I/D polymorphism and BP reduction after treatment. We concluded that the aldosterone synthase -344C/T polymorphism was related to the antihypertensive treatment with telmisartan in hypertensive patients.

Association of mononucleotide polymorphisms of angiotensinogen gene at promoter region with antihypertensive response to angiotensin receptor blockers in hypertensive Chinese.

INTRODUCTION:: This study aimed to investigate whether mononucleotide polymorphisms of the angiotensinogen gene at promoter were associated with the blood-pressure-lowering response to telmisartan treatment. MATERIALS AND METHODS:: After a two-week single-blind placebo run-in period, 148 patients with mild-to-moderate primary hypertension received monotherapy with 80 mg/day of telmisartan and then were followed up for eight weeks. The -6A/G and -20A/C polymorphisms of the angiotensinogen gene at promoter were determined through polymerase chain reaction and restriction fragment length polymorphsim analysis. The relationship between these polymorphisms and changes in blood pressure was observed and evaluated after eight weeks of treatment. RESULTS:: There were no significant differences between -6A/G, -20A/C polymorphisms of the angiotensinogen gene and blood pressure reductions after treatment, p>0.05. CONCLUSION:: It is suggested that angiotensinogen-6 A/G and angiotensinogen-20 A/C polymorphisms were not associated with the antihypertensive response to telmisartan treatment in Chinese patients with hypertension.