99mTc-HFAPi imaging identifies early myocardial fibrosis in the hypertensive heart.

BACKGROUND: This study aimed to explore whether 99mTc-radiolabeled fibroblast activation protein inhibitor (99mTc-HFAPi) imaging can detect early myocardial fibrosis in the hypertensive heart. METHODS: In the experimental model, spontaneously hypertensive rats (SHRs) and age-matched Wistar Kyoto rats (WKYs) were randomly divided into three groups (8, 16, and 28 weeks). The animals underwent 99mTc-HFAPi imaging and echocardiography. Autoradiography and histological analyses were performed in the left ventricle. The mRNA and protein expression level of the fibroblast activation protein (FAP) and collagen I were measured using quantitative PCR and western blot. In the clinical investigation, a total of 106 patients with essential hypertension and 20 gender-matched healthy controls underwent 99mTc-HFAPi imaging and echocardiography. RESULTS: In-vivo and in-vitro autographic images demonstrated diffusely enhanced 99mTc-HFAPi uptake in the SHR heart starting at week 8, before irreversible collagen deposition. The mRNA and protein levels of FAP in SHRs began to increase from week 8, whereas changes in collagen I levels were not detected until week 28. In the clinical investigation, even in hypertensive patients with normal diastolic indicators, normal left ventricular geometry, and normal global longitudinal strain (GLS), the prevalence of increased 99mTc-HFAPi uptake reached 34, 41, and 20%, respectively, indicating that early fibrogenesis precedes structural and functional myocardial abnormalities. CONCLUSION: In hypertension, 99mTc-HFAPi imaging can detect early fibrotic process before myocardial functional and structural changes.

The mediating role of anxiety and depression in the relationship between coping styles and life satisfaction among frontline medical workers during the COVID-19 pandemic: A cross-sectional study.

This study aimed to examine the mediating role of anxiety and depression in the relationship between coping styles and life satisfaction among frontline medical workers during the COVID-19 pandemic. Five hundred and fourteen frontline medical workers from Zunyi were recruited to complete questionnaires, including the Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Satisfaction with Life Scale (SWLS), and Simplified Coping Style Questionnaire (SCSQ). SPSS 24.0 was used to measure the characteristics of anxiety, depression, life satisfaction, and coping styles. We found that the prevalence rates of anxiety and depression among study participants were 22.57% and 18.29%, respectively. Besides, anxiety was positively correlated with depression; anxiety and depression were positively correlated with passive coping style but negatively correlated with life satisfaction and active coping style; life satisfaction was positively correlated with active coping style and negatively correlated with passive coping style (all p < 0.001). Moreover, anxiety and depression mediated the relationship between coping styles and life satisfaction. Anxiety accounted for 18.6% of the effect of active coping style and 35.48% of the effect of passive coping style on life satisfaction. Depression accounted for 48.84% of the effect of active coping style and 67.74% of the effect of passive coping style on life satisfaction. The present study provides novel insights into the effect of subclinical anxiety and depression on frontline medical workers in the pandemic area. Anxiety and depression yielded a mediating effect on the relationship between coping styles and life satisfaction.

Sirtuin 7 serves as a promising therapeutic target for cardiorenal diseases.

Cardiovascular disorders and associated renal diseases account for the main cause of morbidity and mortality worldwide, necessitating the development of novel effective approaches for the prevention and treatment of cardiorenal diseases. Mammalian sirtuins (SIRTs) function as nicotinamide adenine dinucleotide (NAD+)-dependent protein/histone deacetylases. Seven members of SIRTs share a highly invariant catalytic core domain responsible for the specific enzymatic activity. Intriguingly, the broad distribution of SIRTs and alternative isoforms implicate its distinct functions in diverse cardiac and renal cells and tissue types. Notably, SIRT7 has been shown to exert beneficial effects in cardiorenal physiology and pathophysiology via modulation of senescence, DNA damage repair, ribosomal RNA synthesis, protein biosynthesis, angiogenesis, apoptosis, superoxide generation, cardiorenal metabolism, and dysfunction. Furthermore, SIRT7 has emerged as a critical modulator of a broad range of cellular activities including oxidative stress, inflammation response, endoplasmic reticulum stress, and mitochondrial homeostasis, which are all of great significance in postponing the progression of cardiorenal diseases. More importantly, SIRT7 has been implicated in cardiorenal hypertrophy, fibrosis, remodeling, heart failure, atherosclerosis as well as renal acid-base and electrolyte homeostasis as an essential regulator. In this article, we focus on the involvement in cardiorenal physiology and pathophysiology, diverse actions and underlying mechanisms of the SIRT7 signaling, highlighting its updated research progress in heart failure, atherosclerosis, diabetic nephropathy and other cardiorenal diseases. Targeting SIRT7 signaling could be potentially exploited as a therapeutic strategy aiming to prevent and treat cardiorenal diseases.

Declined ELABELA plasma levels in hypertension patients with atrial fibrillation: a case control study.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia in patients with hypertension. ELABELA, which has cardioprotective effects, is decreased in the plasma of patients with hypertension and might be associated with AF in the hypertensive population. This study aims to measure the ELABELA plasma levels in hypertension patients with and without AF and to analyse the related factors. METHODS: A total of 162 hypertension patients with or without AF were recruited for our monocentric observational study. Subjects were excluded if they had a history of valvular heart disease, rheumatic heart disease, cardiomyopathy, thyroid diseases, or heart failure. The patients' histories were recorded, and laboratory examinations were conducted. Plasma ELABELA was detected by immunoassay. Echocardiographs were performed, and parameters were collected by two experienced doctors. Binary logistic regression analysis was used to identify the association between ELABELA plasma level and AF in patients with hypertension. RESULTS: Plasma ELABELA levels were lower in hypertension patients with AF than in those without AF (2.0 [1.5, 2.8] vs. 4.0 [3.4, 5.0] ng/ml, P < 0.001). ELABELA levels were correlated with age, heart rate, BNP levels and left atrial dimension. In addition to the left atrial dimension, ELABELA plasma levels were associated with AF in patients with hypertension (OR 0.081, 95% CI 0.029-0.224, P < 0.001). ELABELA levels were further decreased in the persistent AF subgroup compared with the paroxysmal AF subgroup (1.8 [1.4, 2.5] vs. 2.2 [1.8, 3.0] ng/ml, P = 0.012) and correlated with HR, BNP and ESR levels. CONCLUSIONS: ELALABELA levels were decreased in hypertension patients with AF and further lowered in the persistent AF subgroup. Decreased ELABELA plasma levels were associated with AF in hypertension patients and may be an underlying risk factor.

Does taking an angiotensin inhibitor increase the risk for COVID-19? - a systematic review and meta-analysis.

Because SARS-COV2 entry into cells is dependent on angiotensin converting enzyme 2 (ACE2) and angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) increase ACE2 activity, the safety of ACEI/ARB usage during the coronavirus disease 2019 (COVID-19) pandemic is a controversial topic. To address that issue, we performed a meta-analysis following The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Searches of the Embase, MEDLINE, PubMed, and Cochrane Library databases identified 16 case-control studies examining the effect of ACEI/ARB on the incidence of COVID-19 and its severity. ACEI/ARB usage was associated with an increased risk of COVID-19 morbidity (odds ratio (OR) 1.20, 95% confidence interval (CI) 1.07-1.33, P=0.001) among the general population but not in a hypertensive population (OR 1.05, 95% CI 0.90-1.21, P=0.553). ACEI/ARB usage was not associated with an increased risk of COVID-19 morbidity (coefficient 1.00, 95% CI 1.00-1.00, P=0.660) when we adjusted for hypertension in the general population. ACEI/ARB usage was also not associated with an increased risk of severe illness (OR 0.90, 95%CI 0.55-1.47, P=0.664) or mortality (OR 1.43, 95%CI 0.97-2.10, P=0.070) in COVID-19 patients. Our meta-analysis revealed that ACEI/ARB usage was not associated with either the increased risk of SARS-COV2 infection or the adverse outcomes in COVID-19 patients.

The relationship between serum amyloid A and apolipoprotein A-I in high-density lipoprotein isolated from patients with coronary heart disease.

BACKGROUND: Alteration in the protein composition of high-density lipoprotein (HDL) has been proposed as a mechanism for the development of coronary heart disease (CHD). In HDL, an increase in serum amyloid A protein (SAA) accompanying the decrease in apolipoprotein A-I (apoA-I) has been found during the acute inflammation period. However, whether this phenomenon persists in CHD patients, a disease related to inflammation, is unknown. The purpose of the present study was to explore the relationship between SAA and apoA-I in HDL isolated from CHD patients. METHODS: Overall, 98 patients with confirmed stable CHD and 90 control subjects matched for age and gender were enrolled in this case-control study. Potassium bromide (KBr) density gradient ultracentrifugation was used to isolate HDL from plasma. The levels of SAA and apoA-I in the HDL samples were detected by enzyme-linked immunosorbent assay kits. Pearson's correlation and general linear models were used in the analysis. RESULTS: Compared with controls, patients with CHD had a significant decrease in the amount of apoA-I ((14.21 ± 8.44) µg/ml vs. (10.95 ± 5.95) µg/ml, P = 0.003) in HDL and a significant increase in the amount of log SAA (1.21 ± 0.46 vs. 1.51 ± 0.55, P < 0.00001). Differences were independent of age, body mass index (BMI), HDL cholesterol (HDL-C), and other factors. An independently and statistically significant positive correlation between log SAA and apoA-I in HDL was observed only in the CHD group (ß = 2.0, P = 0.026). In the general linear model, changes in log(SAA), age, age2, gender, BMI and HDL-C could explain a statistically significant 43% of the variance in apoA-I. CONCLUSIONS: This study provides direct evidence for the first time that there was an independent positive correlation between log SAA and apoA-I in the HDL of CHD patients, indicating the alteration of protein composition in HDL. However, the question of whether this alteration in HDL is associated with impairment of HDL functions requires further research.

[Biological characteristics of mesenchymal stem cells in human umbilical cord blood and their supporting capacities in ex vivo expansion of CD34+ hematopoietic stem cells].

OBJECTIVE: To explore the biological characteristics of mesenchymal stem cells (MSC) derived from umbilical cord blood (UCB) and their supporting capacities in ex vivo expansion of hematopoietic stem/progenitor cells (HSPCs). METHODS: Low-density mononuclear cells (MNCs) from UCB were cultured in IMDM containing 20% FBS to form confluent adherent cells through 15 passages. Some cytokines in the conditioned medium were determined with ELISA. UCB-derived adherent cells were displayed with antibodies and analyzed with flow cytometry. The supporting capacity of UCB-derived adherent cells for ex vivo expansion of CD34(+) cells was assayed by co-culture in a two step culture. UCB-derived adherent cells were induced for chondrogenic differentiation with chondrogenic medium, and the induced cells were analyzed for the type II pro-collagen gene expression with RT-PCR. RESULTS: The mean number of adherent fibroblast like colonies derived from UCB was (3.5 +/- 0.7)/10(6) MNCs. UCB-derived MSCs could survive for at least 15 passages of expansion. In their undifferentiated status, UCB-derived MSCs were CD13(+), CD29(+), CD90(+), CD105(+), CD166(+), SH2(+), SH3(+), SH4(+), CD45(-), CD34(-), and CD14(-). Stem cell factor (SCF), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) could be detected in the supernatant of the cultures. The MSCs cultured in chondrogenic media could differentiate into chondrogenic cells and express type II pro-collagen mRNA. UCB-derived MSCs could support the proliferation and differentiation of UCB CD34(+) cells in vitro. CONCLUSION: UCB-derived MSCs are similar to those derived from adult bone marrow and can support the proliferation of hematopoietic stem/progenitor cells.

A protein delivery system: biodegradable alginate-chitosan-poly(lactic-co-glycolic acid) composite microspheres.

In the present study we developed alginate-chitosan-poly(lactic-co-glycolic acid) (PLGA) composite microspheres to elevate protein entrapment efficiency and decrease its burst release. Bovine serum albumin (BSA), which used as the model protein, was entrapped into the alginate microcapsules by a modified emulsification method in an isopropyl alcohol-washed way. The rapid drug releases were sustained by chitosan coating. To obtain the desired release properties, the alginate-chitosan microcapsules were further incorporated in the PLGA to form the composite microspheres. The average diameter of the composite microcapsules was 31+/-9microm and the encapsulation efficiency was 81-87%, while that of conventional PLGA microspheres was just 61-65%. Furthermore, the burst releases at 1h of BSA entrapped in composite microspheres which containing PLGA (50:50) and PLGA (70:30) decreased to 24% and 8% in PBS, and further decreased to 5% and 2% in saline. On the contrary, the burst releases of conventional PLGA microspheres were 48% and 52% in PBS, respectively. Moreover, the release profiles could be manipulated by regulating the ratios of poly(lactic acid) to poly(glycolic acid) in the composite microspheres.

[The experimental study on the idiotypic nucleic Acid vaccine constructed from the genomic DNA to lymphoma].

This study was to investigate the anti-lymphocytic malignancy immunologic effects induced by two types of the idiotypic nucleic acid vaccines which were constructed from the genomic DNA and RNA of the human B lymphoma cell line respectively. Namalwa cell line and BALB/c mice were used as the models. The gene fragments of the IgH variable region (IgHV), which were obtained from the genomic DNA and RNA of Namalwa cell respectively, were cloned into the eukaryocytic expression vector pcDNA 3.0 to be used as the idiotypic nucleic acid vaccines. After transfecting COS cells with one of vaccines constructed from the genomic DNA by using LipofectAMINE, the result of transcription was identified by using RT-PCR. The experimental mice were immunized by intramuscular injection with two types of vaccines. The specific anti-idiotypic antibody was detected by indirect immunofluorescence assay. The results showed that the nucleic acid vaccine constructed from the genomic DNA can be transcribed in COS cells, the transcription product turned shorter, and the intron region of 86 bp was spliced accurately. When immunizing the mice, two vaccines both induced the anti-idiotypic antibody against Namalwa cell, the anti-idiotypic antibody could be detected since detected since after immunization, and got to the peak of titer on the sixth week. It was concluded that the nucleic acid vaccines against lymphoma can be constructed from both the genomic DNA and RNA.