Hederagenin protects against myocardial ischemia-reperfusion injury via attenuating ALOX5-mediated ferroptosis.

Hederagenin (HDG), a medical herb, is known for its beneficial activities against diverse diseases. The cardioprotective effect of HDG has been preliminarily disclosed, but the efficacy and underlying mechanism by which HDG protects against myocardial ischemia-reperfusion (MI/R) injury have not been elucidated yet. To simulate MI/R injury, the left anterior descending artery was occluded for 30 min and then reperfusion for 120 min in a rat model, and the cellular model of hypoxia-reoxygenation (H/R) injury was constructed in H9c2 cardiomyocytes. Hematoxylin-eosin, Prussian blue, and 2,3,5-triphenyl-2H-tetrazolium chloride (TTC) staining were conducted to assess the histological injury, iron deposition, and myocardial infarction. Myocardial enzymes and oxidative stress-related factors were detected using their commercial kits. Lipid peroxidation was measured using BODIPY581/591 probe, and iron content was detected. Cell counting kit (CCK)-8, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), and flow cytometry assays were performed to assess cell viability and apoptosis. Protein levels were investigated by western blot. The interaction between HDG and 5-lipoxygenase (ALOX5) was verified using molecular docking. Our findings indicated that HDG significantly attenuated myocardial dysfunction by reducing infarction and myocardial injury. HDG significantly attenuated myocardial apoptosis in vitro and in vivo, as well as alleviating oxidative stress via reducing reactive oxygen species (ROS) and maintaining the balance between antioxidant and oxidant enzymes. Meanwhile, HDG inhibited I/R-induced ferroptosis in myocardium and cardiomyocytes, including reducing lipid peroxidation and iron level. Moreover, the binding relationship between HDG and ALOX5 was verified, and HDG could concentration dependently downregulate ALOX5. Furthermore, ALOX5 overexpression eliminated the inhibition of HDG on H/R-induced apoptosis, oxidative stress, and ferroptosis in H9c2 cardiomyocytes. HDG ameliorated myocardial dysfunction and cardiomyocyte injury by reducing apoptosis, oxidative stress, and ferroptosis through inhibiting ALOX5, providing a new perspective on the prevention and treatment of MI/R injury.

Development and validation of the systemic lupus erythematous scale amongst the system of quality of life instruments for chronic diseases QLICD-SLE (V2.0).

OBJECTIVE: The present study is aimed to develop and validate a quality of life scale for systemic lupus erythematosus (SLE) patients with Chinese cultural background, QLICD-SLE (V2.0). METHODS: The QLICD-SLE (V2.0) was developed using a systematic approach that involved focus groups, nominal discussions, and pilot testing. A total of 428 SLE patients participated in the scale's assessment. Validity was examined through qualitative analysis, item domain correlation, multidimensional scaling, and factor analysis. Reliability was assessed using Pearson's correlation and Cronbach's alpha coefficients. To evaluate responsiveness, paired T-tests were conducted to compare pre- and post-treatment measurements with the standardised response mean (SRM) being calculated. RESULTS: Correlation and factor analyses demonstrated strong construct validity. When using SF-36 as criteria, the correlation between various domains of QLICD-SLE and SF-36 ranged from 0.55 to 0.70. Test-retest correlation coefficients exceeded 0.71, and Cronbach's alpha coefficients for both measurements in each domain were greater than or equal to 0.75. T-test results showed that both the overall score and most facet scores within each domain showed statistically significant changes after treatment (P < 0.05), indicating reasonable responsiveness. CONCLUSION: The QLICD-SLE (V2.0) appears to be a valid and reliable instrument for assessing the quality of life in patients with SLE.

Up-regulated lncRNA SNHG9 mediates the pathogenesis of dilated cardiomyopathy via miR-326/EPHB3 axis.

Dilated cardiomyopathy (DCM) is a common cause of heart failure and also a major indication for heart transplantation. It has been reported that long non-coding RNAs (lncRNAs) are involved in the development of various cardiac diseases. However, the roles of lncRNAs in DCM are not fully understood. In this study, we uncovered that serum SNHG9 (small nucleolar RNA host gene 9, a lncRNA) serves as a biomarker for dilated cardiomyopathy. GEO datasets (GSE124405) were re-analyzed to identify the aberrant lncRNAs in the plasma sample of patients with heart failure. The receiver operating characteristic (ROC) curve was used to assess the expression alterations of the aberrant lncRNAs including SNHG9, XIST, PLCK2-AS1, KIF9-AS1, ARHGAP31-AS1, LINC00482, etc. Using the area under curve (AUC) of ROC, we found that serum SNHG9 exhibits considerable performance in distinguishing DCM from normal control and DCM stage-III from stage-I/II (New York Heart Association Class). Furthermore, we determined the serum SNHG9 expression level of the doxorubicin (Dox)-induced DCM mice model, and found that the upregulated SNHG9 is negatively associated with heart function. Besides, the deletion of SNHG9 by AAV-9 alleviated heart injury in the Dox-induced mice model. Taken together, the current results suggest that SNHG9 is a novel regulatory factor in dilated cardiomyopathy development.

RIP3 Contributes to Cardiac Hypertrophy by Influencing MLKL-Mediated Calcium Influx.

Receptor-interacting protein 3(RIP3), a RIP family member, has been reported as a critical regulator of necroptosis and involves in the pathogenesis of various heart diseases. However, its role in the development of myocardial hypertrophy after pressure overload is unclear. We aimed to investigate the roles of RIP3 in pathological cardiac hypertrophy. A rat model of myocardial hypertrophy induced by the aortic banding method was used in this study. Neonatal rat cardiomyocytes (NRCMs) were stimulated with angiotensin II (Ang-II) or phenylephrine (PE) to induce neurohumoral stress. Our results showed that RIP3 level was significantly elevated in the hypertrophic myocardium tissues from patients, rats subjected to AB surgery, and NRCMs treated with Ang-II or PE. After downregulation of RIP3 expression in NRCMs, the phenotypes of myocardial hypertrophy were obviously alleviated. In mechanism, we demonstrated that RIP3 interacts with mixed lineage kinase domain-like protein (MLKL) and promotes its cell membrane localization to increase the influx of calcium within cells, thereby mediating the development of myocardial hypertrophy. More interestingly, we found the blockage of calcium influx by 2-aminoethoxydiphenyl borate, and lanthanum chloride efficiently reverses RIP3-induced cardiac remodeling in NRCMs. Taken together, our findings indicate a key role of the RIP3-MLKL signaling pathway in myocardial hypertrophy, which may be a novel promising treatment strategy for myocardial hypertrophy.

MiR-26a-5p alleviates cardiac hypertrophy and dysfunction via targeting ADAM17.

Cardiac hypertrophy has been a high prevalence rate throughout the world. It has posed a big threat to public health due to limited therapeutic approaches. Previous studies showed that pathological cardiac hypertrophy was associated with autophagy, microRNAs (miRNA), and other signaling pathways, while the molecular mechanisms remain incompletely characterized. In this study, we used thoracic aortic constriction (TAC)-induced mice and angiotensin-II (Ang-II)-induced H9C2 cell line as cardiac hypertrophy model to investigate the role of miR-26a-5p in cardiac hypertrophy. We found that miR-26a-5p was downregulated in cardiac hypertrophy mice. Overexpression of miR-26a-5p by type 9 recombinant adeno-associated virus (rAAV9) reversed the heart hypertrophic manifestations. The phenotypes were also promoted by miR-26a-5p inhibitor in Ang-II-induced H9C2 cells. Through miRNA profile analysis and dual-luciferase reporter assay, ADAM17 was identified as a direct target of miR-26a-5p. Restored expression of ADAM17 disrupted the effect of miR-26a-5p on cardiac hypertrophy. To sum up, these results indicated that miR-26a-5p played an inhibitory role in cardiac hypertrophy and dysfunction via targeting ADAM17. The miR-26a-5p-ADAM17-cardiac hypertrophy axis provided special insight and a new molecular mechanism for a better understanding of cardiac hypertrophy disease, as well as the diagnostic and therapeutic practice.

Study on association between shear wave elastography parameters and clinicopathological characteristics in breast cancer: A protocol for systematic review.

BACKGROUND: This study aims to explore the association between shear wave elastography parameters (SWEPs) and clinicopathological characteristics (CPCs) in breast cancer (BC). METHODS: The electronic databases of Cochrane Library, MEDLINE, EMBASE, Allied and Complementary Medicine Database, WANGFANG, VIP, and China National Knowledge Infrastructure will be used to search for studies dated from database inception to the present. No limitations of language and publication status will be applied in this study. Only case-controlled study and randomized controlled trials investigating the association between SWEP and CPC in BC will be included. Cochrane risk of bias will be used to assess study quality for each included study. RevMan 5.3 software will be utilized for statistical analysis. RESULTS: This study will provide accurate data to appraise the association between SWEP and CPC in BC. CONCLUSION: This study will summarize the most recent evidence to improve our understanding of the association between SWEP and CPC in BC. OSF REGISTRATION NUMBER:: osf.io/vmkwu.

LncRNA Tincr regulates PKCɛ expression in a miR-31-5p-dependent manner in cardiomyocyte hypertrophy.

Cardiomyocyte hypertrophy is a fatal factor in heart disease resulting in heart failure and even mortality. Although many studies have been focusing on the pathogenesis of cardiomyocyte hypertrophy, the exact molecular mechanisms are still unexclusive. In this study, we first found that the expression level of lncRNA Tincr was significantly decreased in the myocardial tissues of TAC mouse models of cardiomyocyte hypertrophy, and this result was further confirmed in H9C2 cells, a widely used rat myoblast cell lines. More intriguingly, we demonstrated that the aberration of Tincr is essential to the pathogenesis of cardiomyocyte hypertrophy, indicated by the re-induction of Tincr improving the heart functions of hypertrophic mice. In mechanism, we identified miR-31-5p as a direct target of Tincr using a widely used online bioinformatics tool StarBase, and this result was further experimentally validated using dual-luciferase reporter assay and real-time PCR. Also, we identified PRKCE as a direct target of miR-31-5p, and loss function of miR-31-5p significantly blocks the positive regulatory effect of Tincr on PRKCE expression in H9C2 cells. The knockdown of Tincr resulted in increased cardiomyocyte size, and, however, inhibition of miR-31-5p or overexpression of PRKCE significantly reversed the increased cardiomyocyte size. Taken together, our study showed that a novel Tincr-miR-31-5p axis targeting PRKCE was involved in cardiomyocyte hypertrophy, indicating that it may provide potential therapy in cardiomyocyte hypertrophy.

Behavioral Intention to Initiate Antiretroviral Therapy (ART) Among Chinese HIV-Infected Men Who Have Sex With Men Having High CD4 Count in the Era of "Treatment for All".

China has updated its national guideline recommending antiretroviral therapy (ART) to all people living with HIV (PLWH) since 2016. This study was to investigate the prevalence of behavioral intention to initiate ART among HIV-infected men who have sex with men (MSM) with CD4 levels >350 cells/mm3, who had just become eligible to receive free ART in China. A cross-sectional survey was conducted among 262 eligible HIV-infected MSM who had never received ART. The theory of planned behavior (TPB) was used to guide the variable selection. The prevalence of behavioral intention to initiate ART was 69.9%. After adjusting for significant background variables, all five constructs of TPB were significantly associated with behavioral intention to initiate ART. These significant constructs were: positive attitudes (adjusted odds ratios, AOR: 1.14; 95% CI [1.06, 1.24]) and negative attitudes (AOR: 0.89; 95% CI [0.82, 0.97]) toward immediate ART initiation; perceived their significant others would support them to initiate ART immediately (perceived subjective norm; AOR: 1.14; 95% CI [1.03, 1.25]); perceived high proportion of PLWH having similar CD4 cell levels were on ART (perceived descriptive norm; AOR: 2.22, 95% CI [1.16, 4.24]); and being confident in initiating ART immediately (perceived behavioral control; AOR: 1.21; 95% CI [1.04, 1.39]). Prevalence of behavioral intention to initiate ART was high among this group of MSM. Effective health promotion is needed to translate behavioral intention into related action. TPB may be a useful framework for developing future health promotion increasing ART coverage in this group.