Dysregulated miR-10a-5p is associated with a variety of cardiovascular diseases and fetal growth in the second trimester. This study aimed to investigate the expression and clinical significance of serum miR-10a-5p in patients with hypertension during pregnancy (HDP).

103 healthy pregnant women (control group) and 120 pregnant women with HDP (HDP group) were enrolled in this study. The relative miR-10a-5p was analyzed by qRT-PCR and its association with clinical indicators was performed by Pearson's correlation analysis. The diagnostic and prognostic value were by receiver operator characteristic (ROC) curve and Kaplan-Meier curve analysis, respectively. The risk factor evaluation of HDP was performed by multivariate logistic regression analysis. Adverse pregnancy outcomes were recorded during follow-up.

The miR-10a-5p level was significantly declined in HDP patients compared to control (p < 0.001). The reduced miR-10a-5p was negatively related to SBP (r = -0.6777, p < 0.0001), DBP (r = -0.6026, p < 0.0001), TNF-α (r = -0.7020, p < 0.0001) and IL-6 (r = -0.7149, p < 0.0001). MiR-10-5p was a risk factor of HDP (OR = 0.433, 95% CI: 0.247-0.759, p = 0.003). HDP pregnant women with low miR-10a-5p expression levels (13/68) faced more probability of adverse pregnancy outcomes than those of high miR-10a-5p expression levels (8/52).

Declined miR-10a-5p contributed to the diagnosis and prognosis of HDP and was also a risk factor of HDP.

Public health and clinical guidelines identify the importance of sedentary behaviors for cardiovascular diseases, particularly among postmenopausal women. The goal of this trial was to compare the behavioral and physiological impacts of 2 distinct approaches to changing sedentary behaviors.

Overweight or obese sedentary postmenopausal women (N=407) were randomly assigned to 1 of 3 study conditions for 3 months: (1) healthy living (control), (2) reduce sitting time (sit less), and (3) increase sit-to-stand transitions (STSTs; sit-to-stand). Each study arm received 7 individual health coach sessions across 12 weeks. At baseline and 3 months, participants had fasting blood drawn, had blood pressure measured, and wore thigh (activPal) and hip (ActiGraph) accelerometers for 7 days. Linear mixed models evaluated each intervention arm compared with the control (healthy living) arm.

A total of 388 women (95%) completed the 3-month trial. The sit less arm reduced total sitting time by 58 minutes per day more than the healthy living arm (95% CI, -82.9 to -33.6; P<0.001) but did not change STSTs (-1 STST/day [95% CI, -9.4 to 6.5]; P=0.72). Conversely, the sit-to-stand arm significantly increased STST by 26 STST per day more than the healthy living arm (95% CI, 17.71 to 33.64; P<0.001) but did not differ in change to sitting time (-10 min/day [95% CI, -34.6 to 14.9]; P=0.44). The sit-to-stand arm had significant decreases in diastolic blood pressure compared with the healthy living arm (-2.24 mm Hg [95% CI, -4.08 to -0.40]; P=0.02) and similar decreases in systolic blood pressure compared with the healthy living arm (-3.33 mm Hg [95% CI, -6.32 to -0.33]; P=0.03), although it did not reach the a priori significance threshold of P<0.025. There were no significant intervention effects on blood pressure for the sit less arm and no intervention effects for the glucoregulatory outcomes for either arm.

This trial demonstrated the feasibility of changing sedentary behaviors as well as the distinct nature of sitting time and STST. Increasing STST improved blood pressure in overweight and obese postmenopausal women within 3 months. Focusing on increasing STST may be an achievable behavioral target to reduce cardiovascular disease risk in postmenopausal women.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT03473145.

Ischemic brain injury (IBI) is characterized by high morbidity, disability and mortality rates; however, it lacks effective clinical treatments. Mesenchymal stem cells (MSCs), as pluripotent stem cells with self‑renewal capacity and multilineage differentiation potential, have emerged as a promising therapeutic strategy for neurological disorders. In the present study, in vitro experiments were performed using the Wnt signaling agonist Wnt3a and the B lymphoma Mo‑MLV insertion region 1 homolog (Bmi1) small molecule inhibitor PTC209 to treat MSCs, and the roles and regulatory mechanisms of the Bmi1 and Wnt3a‑RhoA signaling pathways on the neural differentiation of MSCs were explored by MTT assay, immunofluorescence analysis and western blotting. In vivo experiments were also performed by establishing a rat model of middle cerebral artery occlusion (MCAO), transplanting different MSCs into the rat brain tissues after in vitro labeling, and comparing ischemic brain damage in each group of rats by Neurological Severity Score scoring, grasp assay, triphenyltetrazolium chloride staining, hematoxylin and eosin staining, and assessing neurological recovery via immunofluorescence and western blot analysis. The in vivo study aimed to assess the roles of the Bmi1 and Wnt3a‑RhoA signaling pathways in brain injury repair in MCAO rats and the mechanism. Specifically, recombinant Wnt3a cytokine was administered to upregulate the Wnt3a‑RhoA pathway, whereas the small‑molecule inhibitor PTC209 was utilized to suppress Bmi1 expression. The findings suggested that Bmi1 modulates the neural differentiation of MSCs through its regulatory effects on Wnt3a and RhoA expression, thereby influencing the reparative potential of MSCs in ischemic brain tissue. These findings highlight the therapeutic relevance of targeting Wnt3a‑RhoA activation and Bmi1 inhibition in MSC‑based interventions for IBI.

Acute myocarditis encompasses a spectrum of diseases characterized by ongoing inflammation and cardiomyocyte injury, lacking specific diagnostic biomarkers and effective therapies. Transfer RNA (tRNA)‑derived small RNAs (tsRNAs), formed by specific cleavage of tRNAs in response to certain stimuli, participate in diverse diseases; however, their involvement in myocarditis remains unclear. The present study aimed to investigate the role and mechanism of a novel tsRNA, 5'tRNA‑derived stress‑induced RNA (tiRNA)‑Gln‑TTG‑001, in myocarditis. Plasma samples were obtained from patients with acute myocarditis to examine the clinical significance of 5'tiRNA‑Gln‑TTG‑001. AC16 human cardiomyocytes treated with lipopolysaccharide to induce inflammatory responses were utilized to explore the function and mechanism of 5'tiRNA‑Gln‑TTG‑001. Cell viability, apoptosis rates, and levels of factors associated with inflammation (IL‑1β, IL‑6 and IL‑18), myocardial injury (creatine kinase MB and high‑sensitivity cardiac troponin) and myocardial dysfunction (N‑terminal pro‑B‑type natriuretic peptide) were quantified to assess the degree of cardiomyocyte inflammatory injury. RNA fluorescence in situ hybridization (RNA‑FISH), cell transfection, dual‑luciferase reporter assays and functional experiments, including gain‑of‑function and loss‑of‑function assays and rescue experiments, were carried out to further explore the underlying mechanisms. The results revealed that 5'tiRNA‑Gln‑TTG‑001 was upregulated in acute myocarditis and positively correlated with high‑sensitivity cardiac troponin T and T2 ratio. In vitro experiments demonstrated that 5'tiRNA‑Gln‑TTG‑001 aggravated cardiomyocyte inflammatory injury. RNA‑FISH revealed co‑localization of 5'tiRNA‑Gln‑TTG‑001 and chloride intracellular channel 4 (CLIC4) in the nucleus and cytoplasm. Gain‑of‑function and loss‑of‑function experiments revealed that 5'tiRNA‑Gln‑TTG‑001 promoted CLIC4 expression. Dual‑luciferase reporter assays indicated that 5'tiRNA‑Gln‑TTG‑001 activated CLIC4 by binding to its 3'untranslated region. Furthermore, downregulation of CLIC4 rescued cardiomyocyte inflammatory injury aggravated by 5'tiRNA‑Gln‑TTG‑001. Meanwhile, the knockdown of 5'tiRNA‑Gln‑TTG‑001 reduced cardiomyocyte inflammatory injury and the effect was reversed by the upregulation of CLIC4. Overall, the present study demonstrated that 5'tiRNA‑Gln‑TTG‑001 may aggravate cardiomyocyte inflammatory injury via CLIC4 upregulation. Moreover, 5'tiRNA‑Gln‑TTG‑001 could offer a promising option for the diagnosis of myocarditis and serve as a potential therapeutic target.

Vascular calcification (VC) is a pathological condition closely associated with a range of cardiovascular diseases, including atherosclerosis (AS), hypertension, vascular injury, and diabetic angiopathy. Programmed cell death, encompassing apoptosis, autophagy, pyroptosis and ferroptosis, plays a pivotal role in the progression of VC. These cellular processes are intricately regulated by multiple signaling pathways, such as the Wnt/β-catenin and NF-κB pathways, among others. A deeper understanding of the roles and underlying mechanisms of programmed cell death in VC could offer valuable insights for the development of innovative therapeutic strategies targeting cardiovascular diseases.

The removal of excess cholesterol from the body by High-density lipoprotein (HDL) in a process termed reverse cholesterol transport (RCT) has long been proposed to play a critical role in reduction of the lipid burden in arterial wall atherosclerotic lesions. While HDL-cholesterol levels are associated with decreased cardiovascular risk and considered to be "good-cholesterol", clinical studies using HDL-raising therapies to potentially enhance RCT have consistently produced disappointing results. In this mini review we evaluate the effects of human disease on RCT along with the changes in this process upon various therapeutic interventions. Despite the importance of assay standardization, the major method for monitoring RCT has relied upon the cholesterol efflux capacity (CEC) assay, a highly-difficult and tedious cell culture assay, which is low-throughput and only suitable for research studies. Hence, we also briefly review several new methods to measure RCT both in vitro and in vivo, along with new cell-free alternative RCT assays, which have the potential to be developed into routine automated diagnostic assay. The benefits of HDL may yet be revealed by the use of these new high-throughput RCT assays perhaps as a screening tool for novel RCT boosting agents or as new biomarkers for cardiovascular disease risk.

Gout is caused by hyperuricemia and is associated with cardiovascular diseases. Treatment for hyperuricemia primarily involves urate-lowering medications. Some trials showed higher cardiovascular mortality rates with febuxostat compared to allopurinol in gout patients. However, data on the cardiovascular safety of benzbromarone compared to allopurinol is limited, and there is no data comparing benzbromarone to febuxostat. This study aims to assess the cardiovascular safety of benzbromarone, febuxostat, and allopurinol in gout patients.

A comprehensive search was conducted across PubMed and EMBASE from their inception to August 2024. Inclusion criteria were randomized controlled trials (RCTs) and cohort studies including adult patients with the diagnosis of gout, with urate-lowering medications. The outcome was the incidence of major adverse cardiovascular events. This systematic review and network meta-analysis were recorded in INPLASY with the ID INPLASY202460049.

A total of 176 studies were identified through the database search. There were 119 articles identified in EMBASE and 57 articles identified in PubMed. Following screening and review, 17 qualified studies (5 RCTs) were included in the network meta-analysis. The relative cardiovascular event risk (risk ratio, RR) for benzbromarone compared to febuxostat is 0.82 (95% CI 0.61-1.09), and for benzbromarone compared to allopurinol, the RR is 0.87 (95% CI 0.75-1.01). The RR for febuxostat compared to allopurinol is 1.08 (95% CI 0.97-1.20).

Our network meta-analysis suggests a subtle trend indicating a lower risk of cardiovascular events for benzbromarone compared to both febuxostat and allopurinol in gout patients, although not statistically significant.

https://inplasy.com/inplasy-2024-6-0049/, identifier INPLASY202460049.

Traditionally, Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs), a pivotal class of drug, mimics the actions of endogenous Glucagon-like peptide-1, which have been found to be remarkable in the treatment of type 2 diabetes alongside other comorbidities. GLP-1 receptors being widely available in the different organs and tissues such as the brain, lung, pancreas, stomach, heart, and endometrium has explained the broader therapeutic application of GLP-1RA. The recent studies have explored the physiological effects of GLP-1RA on body organs, establishing them as a potential therapeutic option for a wide range of diseases. Activation of GLP-1 receptors contribute to regulation of blood glucose levels, weight management, cardiovascular health, and potential neuroprotection, while also having a positive influence on musculoskeletal health. This review has emphasized the expanded role of GLP-1RA by highlighting the most significant and notable studies. While GLP-1RA has proven clinical efficacy, the need for more comprehensive studies, to ensure their long-term safety, is essential to optimize their therapeutic role and improve patient outcomes on a global scale. Addressing the significant gap for research on cost effectiveness of these drugs is also crucial for their accessibility in comparison to other drugs. Nevertheless, the limited data available calls for a platform for future research to carry out the expanded therapeutic effects of GLP-1RA.

Atherosclerotic cardiovascular disease (ASCVD) pathogenesis is fundamentally driven by dyslipidemia, characterized by lipid metabolism disorders that facilitate cholesterol deposition within damaged vascular endothelia. This process culminates in atherosclerotic plaque formation and coronary stenosis, ultimately inducing myocardial ischemia. While low-density lipoprotein cholesterol (LDL-C) remains the principal lipid determinant of ASCVD progression, emerging evidence indicates persistent residual cardiovascular risk despite optimal statin-mediated LDL-C control. This review aims to systematically evaluate the contributory role of non-traditional lipid biomarkers in ASCVD pathophysiology and clinical outcomes. Through comprehensive analysis of current research, we examine the biological properties and atherogenic mechanisms of non-conventional lipid particles, epidemiological evidence linking these biomarkers with residual cardiovascular risk, and therapeutic implications of targeting alternative lipid pathways. Particular emphasis is placed on elucidating the pathophysiological interplay between triglyceride-rich lipoproteins, lipoprotein(a), and oxidized phospholipids with vascular inflammation and plaque instability. Furthermore, we critically appraise recent clinical trial data regarding novel lipid-modifying agents and propose future research directions to address current knowledge gaps in residual risk management. This synthesis underscores the necessity of expanding therapeutic strategies beyond LDL-C reduction to achieve comprehensive cardiovascular risk mitigation.