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Background Recent studies have reported the effects of metabolic syndrome (MetS) and its components on atrial fibrillation (AF), but the results remain controversial. Therefore, we performed a meta-analysis to evaluate the relationship between MetS and AF risk. Methods Studies were searched from the Cochrane library, PubMed, and Embase databases through May 2020. Adjusted hazard ratios (HRs) and its corresponding 95% confidence intervals (CIs) were extracted and then pooled by using a random effects model. Results A total of 6 observational cohort studies were finally included. In the pooled analysis, MetS was associated with an increased risk of AF (HR 1.57; 95% CI 1.40–1.77; P  < 0.01). And the components of MetS including abdominal obesity (HR 1.37; 95% CI 1.36–1.38; P  < 0.01), elevated blood pressure (HR 1.56; 95% CI 1.46–1.66; P  < 0.01), elevated fasting glucose (HR 1.18; 95% CI 1.15–1.21; P  < 0.01) and low high density cholesterol (HDL) (HR 1.18; 95% CI 1.06–1.32; P  < 0.01) was also associated with an increased risk of AF, while high triglyceride (HR 0.99; 95% CI 0.87–1.11, P  = 0.82) was not. Conclusions Our present meta-analysis suggested that MetS, as well as its components including abdominal obesity, elevated blood pressure, elevated fasting glucose and low HDL cholesterol were associated with an increase in the risk of AF.

Heart failure is the terminal outcome of the majority of cardiovascular diseases, which lacks specific diagnostic biomarkers and therapeutic targets. It contributes to most of cardiovascular hospitalizations and death despite of the current therapy. Therefore, it is important to explore potential molecules improving the diagnosis and treatment of heart failure. MicroRNAs (miRNAs) are small non-coding RNAs that have been reported to be involved in regulating processes of heart failure. After the discovery of miRNAs in exosomes, the subcellular distribution analysis of miRNAs is raising researchers' attention. Growing evidence demonstrates that exosomal miRNAs may be promising diagnostic and therapeutic molecules for heart failure. This review summarizes the role of exosomal miRNAs in heart failure in the prospect of molecular and clinical researches.

Aims Coexisting of atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF) could increase the risk of mortality. In this study, we aimed to assess the values of the CHADS2, R2CHADS2, and CHA2DS2‐VASc scores for AF prediction in HFpEF patients. Methods and results We performed a retrospective analysis on symptomatic HFpEF patients in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial. Associations of the CHADS2, R2CHADS2, and CHA2DS2‐VASc scores with the risk of incident AF in HFpEF patients without baseline AF (n = 2202) were assessed using the multivariable competing risk regression models. The discriminatory performances of these scores were calculated using the C‐index. During a median follow‐up of 3.3 years, the average incidence of AF was 1.80 per 100 patient‐years in HFpEF patients. When score was analysed as a continuous variable, per 1‐point increase in the CHADS2 (hazard ratio [HR] = 1.42, 95% confidence interval [CI]: 1.20–1.68, C‐index: 0.71), R2CHADS2 (HR = 1.25, 95% CI: 1.10–1.42, C‐index: 0.69), or CHA2DS2‐VASc (HR = 1.30, 95% CI: 1.16–1.46, C‐index: 0.70) scores was associated with an increased risk of incident AF. When score was analysed as a categorical variable, patients with CHADS2 ≥ 3 (HR = 2.62, 95% CI: 1.70–4.04), R2CHADS2 ≥ 3 (HR = 2.55, 95% CI: 1.56–4.17), or CHA2DS2‐VASc ≥ 4 (HR = 2.54, 95% CI: 1.59–4.07) had a higher risk of incident AF compared with the corresponding controls. Conclusions Our data first suggest that the CHADS2, R2CHADS2, and CHA2DS2‐VASc scores could predict the risk of incident AF in HFpEF patients with modest predictive abilities.

Cardiac hypertrophy is a pathophysiological response to harmful stimuli. The continued presence of cardiac hypertrophy will ultimately develop into heart failure. The mitochondrion is the primary organelle of energy production, and its dysfunction plays a crucial role in the progressive development of heart failure from cardiac hypertrophy. Hispidulin, a natural flavonoid, has been substantiated to improve energy metabolism and inhibit oxidative stress. However, how hispidulin regulates cardiac hypertrophy and its underlying mechanism remains unknown. We found that hispidulin significantly inhibited pressure overload-induced cardiac hypertrophy and improved cardiac function in vivo and blocked phenylephrine (PE)-induced cardiomyocyte hypertrophy in vitro . We further proved that hispidulin remarkably improved mitochondrial function, manifested by increased electron transport chain (ETC) subunits expression, elevated ATP production, increased oxygen consumption rates (OCR), normalized mitochondrial morphology, and reduced oxidative stress. Furthermore, we discovered that Sirt1, a well-recognized regulator of mitochondrial function, might be a target of hispidulin, as evidenced by its upregulation after hispidulin treatment. Cotreatment with EX527 (a Sirt1-specific inhibitor) and hispidulin nearly completely abolished the antihypertrophic and protective effects of hispidulin on mitochondrial function, providing further evidence that Sirt1 could be the pivotal downstream effector of hispidulin in regulating cardiac hypertrophy.

Individuals with diabetes have a high risk of cardiovascular disease (CVD). However, the association between type 1 diabetes mellitus (T1DM) and the risk of CVD has not been well addressed. This meta-analysis aimed to investigate the association between T1DM and CVD. We searched the PubMed and EMBASE for studies that examined the association between T1DM and CVD until October 2020. We calculated the pooled risk ratios (RRs) with confidence intervals (CIs) from individual studies based on a random-effects model. We included 10 observational studies involving 166,027 patients with T1DM, and individuals were matched controls from the general population. Among T1DM patients, the RR of CVD was 5.09 (95% CI, 3.72–6.96), of coronary heart disease (CHD) was 9.38 (95% CI, 5.56–15.82), and of myocardial infarction was 6.37 (95% CI, 3.81–10.66). The RR of heart failure was 4.29 (95% CI, 3.54–5.19), of atrial fibrillation was 1.36 (95% CI, 1.17–1.59), and of stroke was 4.08 (95% CI, 3.42–4.86). Moreover, there was an increased RR among females for CHD, CVD, myocardial infarction, and stroke associated with T1DM. This study suggests that T1DM is associated with an increased risk of several types of CVD. However, the possible mechanisms for the increased risk of CVD remain unclear. •T1DM is associated with an increased risk of several types of CVD.•There was an increased RR among females for CHD, CVD, myocardial infarction, and stroke associated with T1DM.

As a major public health problem, the prevalence of Acinetobacter baumannii (A. baumannii) infections in hospitals due to the pathogen’s multiple-antibiotic resistance has attracted extensive attention. We previously reported a series of 1,3-diamino-7H-pyrrolo[3,2-f]quinazoline (PQZ) compounds, which were designed by targeting Escherichia coli dihydrofolate reductase (ecDHFR), and exhibited potent antibacterial activities. In the current study, based on our molecular-modeling study, it was proposed that PQZ compounds may function as potent A. baumannii DHFR (abDHFR)-inhibitors as well, which inspired us to consider their anti-A. baumannii abilities. We further found that three PQZ compounds, OYYF-171, -172, and -175, showed significant antibacterial activities against A. baumannii, including multidrug-resistant (MDR) strains, which are significantly stronger than the typical DHFR-inhibitor, trimethoprim (TMP), and superior to, or comparable to, the other tested antibacterial agents belonging to β-lactam, aminoglycoside, and quinolone. The significant synergistic effect between the representative compound OYYF-171 and the dihydropteroate synthase (DHPS)-inhibitor sulfamethoxazole (SMZ) was observed in both the microdilution-checkerboard assay and time-killing assay, which indicated that using SMZ in combination with PQZ compounds could help to reduce the required dosage and forestall resistance. Our study shows that PQZ is a promising scaffold for the further development of folate-metabolism inhibitors against MDR A. baumannii.

As a major public health problem, the prevalence of Acinetobacter baumannii (A. baumannii) infections in hospitals due to the pathogen's multiple-antibiotic resistance has attracted extensive attention. We previously reported a series of 1,3-diamino-7H-pyrrolo[3,2-f]quinazoline (PQZ) compounds, which were designed by targeting Escherichia coli dihydrofolate reductase (ecDHFR), and exhibited potent antibacterial activities. In the current study, based on our molecular-modeling study, it was proposed that PQZ compounds may function as potent A. baumannii DHFR (abDHFR)-inhibitors as well, which inspired us to consider their anti-A. baumannii abilities. We further found that three PQZ compounds, OYYF-171, -172, and -175, showed significant antibacterial activities against A. baumannii, including multidrug-resistant (MDR) strains, which are significantly stronger than the typical DHFR-inhibitor, trimethoprim (TMP), and superior to, or comparable to, the other tested antibacterial agents belonging to β-lactam, aminoglycoside, and quinolone. The significant synergistic effect between the representative compound OYYF-171 and the dihydropteroate synthase (DHPS)-inhibitor sulfamethoxazole (SMZ) was observed in both the microdilution-checkerboard assay and time-killing assay, which indicated that using SMZ in combination with PQZ compounds could help to reduce the required dosage and forestall resistance. Our study shows that PQZ is a promising scaffold for the further development of folate-metabolism inhibitors against MDR A. baumannii.As a major public health problem, the prevalence of Acinetobacter baumannii (A. baumannii) infections in hospitals due to the pathogen's multiple-antibiotic resistance has attracted extensive attention. We previously reported a series of 1,3-diamino-7H-pyrrolo[3,2-f]quinazoline (PQZ) compounds, which were designed by targeting Escherichia coli dihydrofolate reductase (ecDHFR), and exhibited potent antibacterial activities. In the current study, based on our molecular-modeling study, it was proposed that PQZ compounds may function as potent A. baumannii DHFR (abDHFR)-inhibitors as well, which inspired us to consider their anti-A. baumannii abilities. We further found that three PQZ compounds, OYYF-171, -172, and -175, showed significant antibacterial activities against A. baumannii, including multidrug-resistant (MDR) strains, which are significantly stronger than the typical DHFR-inhibitor, trimethoprim (TMP), and superior to, or comparable to, the other tested antibacterial agents belonging to β-lactam, aminoglycoside, and quinolone. The significant synergistic effect between the representative compound OYYF-171 and the dihydropteroate synthase (DHPS)-inhibitor sulfamethoxazole (SMZ) was observed in both the microdilution-checkerboard assay and time-killing assay, which indicated that using SMZ in combination with PQZ compounds could help to reduce the required dosage and forestall resistance. Our study shows that PQZ is a promising scaffold for the further development of folate-metabolism inhibitors against MDR A. baumannii.

As a major public health problem, the prevalence of Acinetobacter baumannii (A. baumannii) infections in hospitals due to the pathogen’s multiple-antibiotic resistance has attracted extensive attention. We previously reported a series of 1,3-diamino-7H-pyrrolo[3,2-f]quinazoline (PQZ) compounds, which were designed by targeting Escherichia coli dihydrofolate reductase (ecDHFR), and exhibited potent antibacterial activities. In the current study, based on our molecular-modeling study, it was proposed that PQZ compounds may function as potent A. baumannii DHFR (abDHFR)-inhibitors as well, which inspired us to consider their anti-A. baumannii abilities. We further found that three PQZ compounds, OYYF-171, -172, and -175, showed significant antibacterial activities against A. baumannii, including multidrug-resistant (MDR) strains, which are significantly stronger than the typical DHFR-inhibitor, trimethoprim (TMP), and superior to, or comparable to, the other tested antibacterial agents belonging to β-lactam, aminoglycoside, and quinolone. The significant synergistic effect between the representative compound OYYF-171 and the dihydropteroate synthase (DHPS)-inhibitor sulfamethoxazole (SMZ) was observed in both the microdilution-checkerboard assay and time-killing assay, which indicated that using SMZ in combination with PQZ compounds could help to reduce the required dosage and forestall resistance. Our study shows that PQZ is a promising scaffold for the further development of folate-metabolism inhibitors against MDR A. baumannii.