Mechanisms involved in the regulation of mitochondrial quality control by PGAM5 in heart failure.

Heart failure (HF) refers to a group of clinical syndromes in which various heart diseases lead to the inability of cardiac output to meet the metabolic needs of the body's tissues. Cardiac metabolism requires enormous amounts of energy; thus, impaired myocardial energy metabolism is considered a key factor in the occurrence and development of HF. Mitochondria serve as the primary energy source for cardiomyocytes, and their regular functionality underpins healthy cardiac function. The mitochondrial quality control system is a crucial mechanism for regulating the functionality of cardiomyocytes, and any abnormality in this system can potentially impact the morphology and structure of mitochondria, as well as the energy metabolism of cardiomyocytes. Phosphoglycerate mutase 5 (PGAM5), a multifunctional protein, plays a key role in the regulation of mitochondrial quality control through multiple pathways. Therefore, abnormal PGAM5 function is closely related to mitochondrial damage. This article reviews the mechanism of PGAM5's involvement in the regulation of the mitochondrial quality control system in the occurrence and development of HF, thereby providing a theoretical basis for future in-depth research.

Exploring T7 RNA polymerase-assisted CRISPR/Cas13a amplification for the detection of BNP via electrochemiluminescence sensing platform.

Brain natriuretic peptide (BNP) is considered to be an important biomarker of heart failure (HF) attracting attention. However, its low concentration and short half-life in blood lead to a low-sensitivity detection of BNP, which is a challenge that has to be overcome. In this work, we propose a highly specific, highly sensitive T7 RNA polymerase-assisted clustered regularly interspaced short palindromic repeats (CRISPR)/Cas13a system to detect BNP via an electrochemiluminescence (ECL) sensing platform and incorporate exonuclease III (Exo III)-hairpin and dumbbell-shaped hybridization chain reaction (HCR) technologies. In this detection scheme, the ECL sensing platform possesses low background signal and high sensitivity. Firstly, the T7 promoter-initiated T7 RNA polymerase acts as a signal amplification technique to generate large amounts of RNAs that can activate CRISPR/Cas13a activity. Secondly, CRISPR/Cas13a is able to trans-cleave the surrounding trigger strand to produce DNA1. Thirdly, DNA1 is involved in the co-amplification reaction of Exo III and hairpin DNA, which subsequently triggers a dumbbell-shaped HCR technology. Eventually, a large number of Ru (II) molecules are inserted into the interstitial space of the dumbbell-shaped HCR to generate a strong ECL signal. The CRISPR/Cas13a possesses outstanding specificity for a single base and increased sensitivity. The tightly conformed dumbbell-shaped HCR provides higher sensitivity than the traditional linear HCR amplification technique. Ultimately, the clever combination of several amplification reactions enables the limit of detection (LOD) as low as 3.2 fg/mL. It showed promise for clinical sample testing, with recovery rates ranging from 98.4% to 103% in 5% human serum samples. This detection method offered a valuable tool for early HF detection, emphasizing the synergy of amplification strategies and specificity conferred by CRISPR/Cas13a technology.

Evaluation of Chlamydia trachomatis screening from the perspective of health economics: a systematic review.

Background: Most Chlamydia trachomatis (CT) infections are asymptomatic. The infection can persist and lead to severe sequelae. Therefore, screening for CT can primarily prevent serious sequelae. Aim: To systematically evaluate CT screening from the perspective of health economics, summarize previous findings from different target populations, and make practical recommendations for developing local CT screening strategies. Methods: PubMed, Web of Science, Embase, Cochran Library, and National Health Service Economic Evaluation Database (Ovid) were searched from January 1, 2000, to March 4, 2023. Studies reporting the cost-effectiveness, cost-benefit, or cost-utility of CT screening were eligible to be included. A narrative synthesis was used to analyze and report the results following the PRISMA guidelines. The Consensus on Health Economic Criteria (CHEC) list was used to assess the methodological quality of included studies. Results: Our review finally comprised 39 studies addressing four populations: general sexually active people (n = 25), pregnant women (n = 4), women attending STD and abortion clinics (n = 4), and other high-risk individuals (n = 6). The total number of participants was ~7,991,198. The majority of studies assessed the cost-effectiveness or cost-utility of the screening method. The results showed that the following screening strategies may be cost-effective or cost-saving under certain conditions: performing CT screening in young people aged 15-24 in the general population, military recruits, and high school students; incorporating CT screening into routine antenatal care for pregnant women aged 15-30; opportunistic CT screening for women attending STD and abortion clinics; home-obtained sampling for CT screening using urine specimens or vaginal swab; performing CT screening for 14-30-year-old people who enter correctional institutions (i.e., jail, detention) as soon as possible; providing CT screening for female sex workers (FSWs) based on local incidence and prevalence; adding routine CT screening to HIV treatment using rectal samples from men who have sex with men (MSM). Conclusion: We found that CT screening in general sexually active people aged 15-24, military recruits, high school students, pregnant women aged 15-30, women attending STD and abortion clinics, people entering jail, detention, FSWs, and MSM has health economic value. Due to the different prevalence of CT, diversities of economic conditions, and varying screening costs among different populations and different countries, regions, or settings, no uniform and standard screening strategies are currently available. Therefore, each country should consider its local condition and the results of health economic evaluations of CT screening programs in that country to develop appropriate CT screening strategies.

Challenges of epidemiological investigation work in the COVID-19 pandemic: a qualitative study of the epidemiology workforce in Guangdong Province, China.

OBJECTIVES: This study sought to identify the epidemiological investigation challenges of the COVID-19 pandemic and offer insights into the underlying issues. DESIGN: An exploratory qualitative study used thematic analysis of semistructured and in-depth individual interviews. SETTING: This study was conducted in Centers for Disease Control and Prevention in Guangdong Province. PARTICIPANTS: Twenty-four participants consented to participate in an in-depth interview. Transcribed recordings were managed using NVivo software and analysed using inductive thematic analysis. RESULTS: The qualitative analysis revealed five key themes: high-intensity epidemiological investigation task, emergency management requiring improvement in the early stage, respondent uncertainty, impact on work and social life and inadequate early-stage Joint Prevention and Control Mechanism. CONCLUSION: This survey focuses on the epidemiology workforce at the forefront of the COVID-19 pandemic and qualitatively describes their experiences, vocational issues and psychological stressors. We found that the problems of epidemiological investigation posed intense challenges to the epidemiology workforce. These findings highlight the epidemiological investigation challenges associated with this pandemic. We have provided some suggestions that may help improve the efficiency and quality of the epidemiology workforce in China.

Fluid Shear Stress Ameliorates Prehypertension-Associated Decline in Endothelium-Reparative Potential of Early Endothelial Progenitor Cells.

This study investigated the effects of prehypertension and shear stress on the reendothelialization potential of human early EPCs and explored its potential mechanisms. Early EPCs from the prehypertensive patients showed reduced migration and adhesion in vitro and demonstrated a significantly impaired in vivo reendothelialization capacity. Shear stress pretreatment markedly promoted the in vivo reendothelialization capacity of EPCs. Although basal CXCR4 expression in early EPCs from prehypertensive donors was similar to that from healthy control, SDF-1-induced phosphorylation of CXCR4 was lower in prehypertensive EPCs. Shear stress up-regulated CXCR4 expression and increased CXCR4 phosphorylation, and restored the SDF-1/CXCR4-dependent JAK-2 phosphorylation in prehypertensive EPCs. CXCR4 knockdown or JAK-2 inhibitor treatment prevents against shear stress-induced increase in the migration, adhesion and reendothelialization capacity of the prehypertensive EPCs. Collectively, CXCR4 receptor profoundly modulates the reendothelialization potential of early EPCs. The abnormal CXCR4-mediated JAK-2 signaling may contribute to impaired functions of EPCs from patients with prehypertension.

Integrated Strategies of Diverse Feature Selection Methods Identify Aging-Based Reliable Gene Signatures for Ischemic Cardiomyopathy.

Objective: Ischemic cardiomyopathy (ICM) is a major cardiovascular state associated with prominently increased morbidity and mortality. Our purpose was to detect reliable gene signatures for ICM through integrated feature selection strategies. Methods: Transcriptome profiles of ICM were curated from the GEO project. Classification models, including least absolute shrinkage and selection operator (LASSO), support vector machine (SVM), and random forest, were adopted for identifying candidate ICM-specific genes for ICM. Immune cell infiltrates were estimated using the CIBERSORT method. Expressions of candidate genes were verified in ICM and healthy myocardial tissues via Western blotting. JC-1 staining, flow cytometry, and TUNEL staining were presented in hypoxia/reoxygenation (H/R)-stimulated H9C2 cells with TRMT5 deficiency. Results: Following the integration of three feature selection methods, we identified seven candidate ICM-specific genes including ASPN, TRMT5, LUM, FCN3, CNN1, PCNT, and HOPX. ROC curves confirmed the excellent diagnostic efficacy of this combination of previous candidate genes in ICM. Most of them presented prominent interactions with immune cell infiltrates. Their deregulations were confirmed in ICM than healthy myocardial tissues. TRMT5 expressions were remarkedly upregulated in H/R-stimulated H9C2 cells. TRMT5 deficiency enhanced mitochondrial membrane potential and reduced apoptosis in H/R-exposed H9C2 cells. Conclusion: Collectively, our findings identified reliable gene signatures through combination strategies of diverse feature selection methods, which facilitated the early detection of ICM and revealed the underlying mechanisms.

LncRNA PVT1 Knockdown Ameliorates Myocardial Ischemia Reperfusion Damage via Suppressing Gasdermin D-Mediated Pyroptosis in Cardiomyocytes.

Objective: Myocardial ischemia reperfusion (I/R) damage is a life-threatening vascular emergency after myocardial infarction. Here, we observed the cardioprotective effect of long non-coding RNA (lncRNA) PVT1 knockdown against myocardial I/R damage. Methods: This study constructed a myocardial I/R-induced mouse model and a hypoxia/reoxygenation (H/R)-treated H9C2 cells. PVT1 expression was examined via RT-qPCR. After silencing PVT1 via shRNA against PVT1, H&E, and Masson staining was performed to observe myocardial I/R damage. Indicators of myocardial injury including cTnI, LDH, BNP, and CK-MB were examined by ELISA. Inflammatory factors (TNF-α, IL-1ß, and IL-6), Gasdermin D (GSDMD), and Caspase1 were detected via RT-qPCR, western blot, immunohistochemistry, or immunofluorescence. Furthermore, CCK-8 and flow cytometry were presented for detecting cell viability and apoptosis. Results: LncRNA PVT1 was markedly up-regulated in myocardial I/R tissue specimens as well as H/R-induced H9C2 cells. Silencing PVT1 significantly lowered serum levels of cTnI, LDH, BNP, and CK-MB in myocardial I/R mice. H&E and Masson staining showed that silencing PVT1 alleviated myocardial I/R injury. PVT1 knockdown significantly lowered the production and release of inflammatory factors as well as inhibited the expression of GSDMD-N and Caspase1 in myocardial I/R tissue specimens as well as H/R-induced H9C2 cells. Moreover, silencing PVT1 facilitated cell viability and induced apoptosis of H/R-treated H9C2 cells. Conclusion: Our findings demonstrated that silencing PVT1 could alleviate myocardial I/R damage through suppressing GSDMD-mediated pyroptosis in vivo and in vitro. Thus, PVT1 knockdown may offer an alternative therapeutic strategy against myocardial I/R damage.

Bisphenol Analogues and Their Chlorinated Derivatives in Breast Milk in China: Occurrence and Exposure Assessment.

Concentrations of bisphenol A (BPA) and its analogues (together with their chlorinated derivatives are referred to as BPs) were measured in 181 breastmilk samples collected from 9 provinces in China in 2014. Twelve BP types were found. The BP concentrations ranged from not detected to 5.912 µg/L. BPA was the predominant BP, followed by bisphenol F (BPF) and bisphenol S (BPS). The mean BPA, BPF, and BPS levels were 0.444, 0.107, and 0.027 µg/L, respectively. Other BPs were sporadically detected in breastmilk samples. There were no differences (p > 0.05) in BPA, BPF, BPS, or total BP levels in the urban and rural regions or the northern and southern regions. BPA accounted for approximately 70% of the BPs and BPF accounted for more than 20% of the BPs in breast milk samples. The high contribution of BPF indicated that BPA analogues, not only BPA, should receive attention. The upper-bound daily intakes of BPs for infants 0-6 months old were 0.044-1.291 µg/kg bw/day. Despite the absence of tolerable daily intake data, attention should be paid not only on BPA but also BPF.

Downregulation of Uncoupling Protein 2(UCP2) Mediated by MicroRNA-762 Confers Cardioprotection and Participates in the Regulation of Dynamic Mitochondrial Homeostasis of Dynamin Related Protein1 (DRP1) After Myocardial Infarction in Mice.

Acute myocardial infarction (MI) is one of the leading causes of death in the world, and its pathophysiological mechanisms have not been fully elucidated. The purpose of this study was to investigate the role and mechanism of uncoupling protein 2 (UCP2) after MI in mouse heart. Here, we examined the expression and role of UCP2 in mouse heart 4 weeks after MI. The expression of UCP2 was detected by RT-PCR and western blotting. Cardiac function, myocardial fibrosis, and cardiomyocyte apoptosis were assessed by echocardiography and immunohistochemistry. Phosphatase dynamin-related protein1 (P-DRP1) and myocardial fibrosis-related proteins were measured. Cardiomyocytes were exposed to hypoxia for 6 h to mimic the model of MI. Mdivi, an inhibitor of P-DRP1, was used to inhibit DRP1-dependent mitochondrial fission. Mitochondrial superoxide, membrane potential, oxygen consumption rate, and cardiomyocyte apoptosis were detected after hypoxia. It is shown mitochondrial superoxide, membrane potential, oxygen consumption rate, and cardiomyocyte apoptosis were dependent on the level of P-DRP1. UCP2 overexpression reduced cardiomyocyte apoptosis (fibrosis), improved cardiac function and inhibit the phosphorylation of DRP1 and the ratio of P-DRP1/DRP1. However, inhibition of DRP1 by mdivi did not further reduce cell apoptosis rate and cardiac function in UCP2 overexpression group. In addition, bioinformatics analysis, luciferase activity, and western blot assay proved UCP2 was a direct target gene of microRNA-762, a up-regulated microRNA after MI. In conclusion, UCP2 plays a protective role after MI and the mechanism is involved in microRNA-762 upstream and DRP1-dependent mitochondrial fission downstream.

[Association between hemoglobin scavenger receptor CD163 expression and coronary atherosclerotic severity in patients with coronary heart disease].

OBJECTIVE: To investigate the association between hemoglobin scavenger receptor (CD163) expression levels on monocytic surfaces and coronary atherosclerotic severity in patients with coronary heart disease (CHD) as well as the roles of CD163 in inflammation and lipidperoxidation. METHODS: Eighty-four patients were diagnosed as CHD according to the results of coronary angiography and ACC/AHA diagnostic criteria. The patients were divided into 3 groups: acute myocardial infarction (AMI) group (n = 30), unstable angina (UA) group (n = 30), stable angina (SA) group (n = 24). Another 20 patients with normal coronary artery served as control. Expression levels of CD163 on monocytes were detected by means of flow cytometry, and the results were shown as mean fluorescence intensity (mfi). All patients underwent coronary angiography and the results were further evaluated by Jenkins score. Serum CRP and LDL-C were also measured. RESULTS: The expression levels of CD163 on monocytes in peripheral blood were significantly higher in CHD patients compared to controls (P < 0.01) in the order of AMI group [(84.4 +/- 6.9) mfi] > UA group [(64.1 +/- 5.5) mfi, P < 0.01 vs. AMI] > SA group [(46.7 +/- 6.5) mfi, P < 0.01 vs. AMI and UA] > control group [(22.0 +/- 6.1) mfi, P < 0.01 vs. AMI, UA and SA]. The expression levels of CD163 on monocytes in patients with CHD were positively correlated with Jenkins score (r = 0.9107, P < 0.01), CRP (r = 0.766, P < 0.01) and LDL-C (r = 0.749, P < 0.01). CONCLUSIONS: Expression levels of CD163 was significantly increased in patients with CHD and positively correlated with coronary heart disease severity and serum CRP and LDL-C.