LncRNA JPX targets SERCA2a to mitigate myocardial ischemia/reperfusion injury by binding to EZH2.

Long non-coding RNAs (lncRNAs) are pivotal regulators in heart disease, including myocardial ischemia/reperfusion (I/R) injury. LncRNA just proximal to XIST (JPX) is a molecular switch for X-chromosome inactivation. Enhancer of zeste homolog 2 (EZH2) is a core catalytic subunit of the polycomb repressive complex 2 (PRC2), which is involved in chromatin compaction and gene repression. This study aims to explore the mechanism of JPX regulating the expression of Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) by binding to EZH2 and preventing cardiomyocyte I/R damage in vivo and in vitro. First, we constructed mouse myocardial I/R and HL1 cell hypoxia/reoxygenation models, and found that JPX was low expressed in both models. JPX overexpression alleviated cardiomyocyte apoptosis in vivo and in vitro, reduced the I/R-induced infarct size in mouse hearts, lowered the serum cTnI concentration, and promoted mouse cardiac systolic function. The evidence implies that JPX can alleviate I/R-induced acute cardiac damage. Mechanistically, the FISH and RIP assays showed that JPX could bind to EZH2. The ChIP assay revealed EZH2 enrichment at the promoter region of SERCA2a. Both the EZH2 and H3K27me3 levels at the promoter region of SERCA2a were reduced in the JPX overexpression group compared to those in the Ad-EGFP group (P < 0.01). In summary, our results suggested that LncRNA JPX directly bound to EZH2 and reduced the EZH2-mediated H3K27me3 in the SERCA2a promoter region, protecting the heart from acute myocardial I/R injury. Therefore, JPX might be a potential therapeutic target for I/R injury.

Self-Reported Vision Loss, Health Status, and Social Participation Among Middle-Aged and Older Adults-Evidence From China.

Social participation is crucial for enhancing senior's well-being and promoting their integration into society. Using nationwide data investigated in China, this study explored the association between self-reported visual impairment, health level, and social participation among Chinese middle-aged old adults. It has been found that (a) the probability and frequency of social participation among middle-aged and older adults with self-reported vision loss were significantly lower than those without vision problems; (b) self-reported vision loss was negatively associated with self-rated health and mental health status, and both were positively associated with social participation; and (c) self-rated health and mental health played a mediating role between vision loss and social participation. The findings suggest that under the framework of active aging, universal vision screening programs and rehabilitation plans for the older adults with visual impairment are exceedingly significant to promote their participation in social activities, thereby enhancing their quality of life.

The biological function and potential mechanism of long non-coding RNAs in cardiovascular disease.

Long non-coding RNAs (lncRNAs), as part of the family of non-protein-coding transcripts, are implicated in the occurrence and progression of several cardiovascular diseases (CVDs). With recent advances in lncRNA research, these molecules are purported to regulate gene expression at multiple levels, thereby producing beneficial or detrimental biological effects during CVD pathogenesis. At the transcriptional level, lncRNAs affect gene expression by interacting with DNA and proteins, for example, components of chromatin-modifying complexes, or transcription factors affecting chromatin status. These potential mechanisms suggest that lncRNAs guide proteins to specific gene loci (eg promoter regions), or forestall proteins to specific genomic sites via DNA binding. Additionally, some lncRNAs are required for correct chromatin conformation, which occurs via chromatin looping in enhancer-like models. At the post-transcriptional level, lncRNAs interact with RNA molecules, mainly microRNAs (miRNAs) and mRNAs, potentially regulating CVD pathophysiological processes. Moreover, lncRNAs appear to post-transcriptionally modulate gene expression by participating in mRNA splicing, stability, degradation and translation. Thus, the purpose of this review is to provide a comprehensive summary of lncRNAs implicated in CVD biological processes, with an emphasis on potential mechanisms of action.

Environmental and Climate Impacts on Physiological Aging: Comprehensive Pathways to Enhanced Age-related Resilience.

This perspective article highlights the pressing necessity to focus on heterogeneity in organ-specific aging, emphasizing the influence of environmental and climate changes, as well as social interactions, on the aging process of individual organs. It explores innovative and integrative strategies tailored to the unique aging mechanisms of different organs, aiming to preserve their biological clocks. By emphasizing the importance of addressing organ-specific vulnerabilities, the article calls for transcending traditional pharmacological treatments and organ transplants. It proposes a comprehensive approach that combines environmental management, social support systems, and advanced technological interventions to improve the well-being and longevity of aging populations.

Delta Radiomics Model for the Prediction of Overall Survival and Local Recurrence in Small Cell Lung Cancer Patients After Chemotherapy.

RATIONALE AND OBJECTIVES: To evaluate the validity of CT-based delta radiomics signatures in predicting overall survival (OS) and local recurrence (LR) in small cell lung cancer (SCLC) patients after chemotherapy. MATERIALS AND METHODS: Retrospectively enrolled 136 SCLC patients were split into training and testing cohorts. Radiomics features were extracted from CT images before, after the second, and the fourth cycle of chemotherapy. Delta radiomics features were obtained by calculating the net changes of features. Three radiomics signatures (R1, R2, and R3) and three delta radiomics signatures (R21, R31, and R32) were developed. The best signature was defined as the radiomics risk signature (RRS). The significant clinicoradiological factors and RRS of OS or LR were applied to build the combined model. RRS was also investigated in the subgroups based on stage and treatment regimens, respectively. RESULTS: Delta radiomics models presented improved performance. R32 signature demonstrated the highest C-indices in the training and testing cohorts, with C-indices of 0.850 and 0.834 in the OS arm, and 0.723 and 0.737 in the LR arm, respectively. The incremental performance was observed after the clinicoradiological characteristics integrated into the RRSOS, with C-indexes of 0.857 and 0.836, respectively. Furthermore, the stratified analysis also confirmed the ability of RRS based on the stage and treatment regimen subgroups in the OS and LR arms, respectively. CONCLUSION: Delta radiomics signatures could improve the personalized prediction of OS and LR at the early stage of chemotherapy in SCLC patients. R32 signature performed the highest performance.

m6A RNA Methylation Decreases Atherosclerotic Vulnerable Plaque Through Inducing T Cells.

INTRODUCTION: Knockdown of fat mass and obesity-associated gene (FTO) can induce N6-methyladenosine (m6A) ribonucleic acid (RNA) methylation. The objective of this study was to explore the effect of m 6A RNA methylation on atherosclerotic vulnerable plaque by FTO knockdown. METHODS: A total of 50 New Zealand white rabbits were randomly divided into pure high-fat group, sham operation group, vulnerable plaque group, empty load group, and FTO knockdown group (10 rabbits/group). RESULTS: Flow cytometry showed that helper T (Th) cells in the FTO knockdown group accounted for a significantly higher proportion of lymphocytes than in the vulnerable plaque group and empty load group (P<0.05). Th cells were screened by cell flow. The level of m6A RNA methylation in the FTO knockdown group was significantly higher than in the vulnerable plaque group and empty load group (P<0.05). The levels of total cholesterol, triglyceride, and low-density lipoprotein C were higher at the 12th week than at the 1st week, but the high-density lipoprotein C level was lower at the 12th week than at the 1st week. At the 12th week, the interleukin-7 level was significantly lower in the adeno-associated virus-9 (AVV9)-FTO short hairpin RNA group than in the control and AVV9-green fluorescent protein groups (P<0.001). CONCLUSION: After successfully establishing a vascular parkinsonism rabbit model, m6A RNA methylation can decrease Th cells and vulnerable atherosclerotic plaques.

Prediction of the Old-Age Dependency Ratio in Chinese Cities Using DMSP/OLS Nighttime Light Data.

The old-age dependency ratio (ODR) is an important indicator reflecting the degree of a regional population's aging. In the context of aging, this study provides a timely and effective method for predicting the ODR in Chinese cities. Using the provincial ODR from the Seventh National Population Census and Defense Meteorological Satellite Program/Operational Linescan System (DMSP/OLS) nighttime light data, this study aims to predict and analyze the spatial correlation of the municipal ODR in Chinese cities. First, the prediction model of the ODR was established with curve regression. Second, the spatial structure of the municipal ODR was investigated using the Moran's I method. The experimental results show the following: (1) the correlation between the sum of the nighttime light and ODR is greater than the mean of nighttime light in the study areas; (2) the Sigmoid model fits better than other regression models using the provincial ODR in the past ten years; and (3) there exists an obvious spatial agglomeration and dependence on the municipal ODR. The findings indicate that it is reasonable to use nighttime light data to predict the municipal ODR in large and medium-sized cities. Our approach can provide support for future regional censuses and spatial simulations.

Luteolin modulates SERCA2a via Sp1 upregulation to attenuate myocardial ischemia/reperfusion injury in mice.

The sarco/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) is responsible for calcium transport during excitation-contraction coupling and is essential for maintaining myocardial systolic/diastolic function and intracellular Ca2+ levels. Therefore, it is important to investigate mechanisms whereby luteolin modulates SERCA2a expression to attenuate myocardial ischemia/reperfusion injury. C57BL/6j mice were randomly divided into eight groups. The expression and activity of SERCA2a was measured to assess interactions between the SERCA2a promoter and the Sp1 transcription factor, and the regulatory effects of luteolin. We used serum LDH release, serum cardiac troponin I level, hemodynamic data, myocardial infarction size and apoptosis-related indices to measure SERCA2a cardio-protective effects of luteolin pretreatment. Sp1 binding to SERCA2a promoter under ischemia/reperfusion conditions in the presence or absence of luteolin was analyzed by chromatin immunoprecipitation. Our experimental results indicated that during myocardial ischemia/reperfusion injury, luteolin pretreatment upregulated the expression levels of SERCA2a and Sp1. Sp1 overexpression enhanced the expression of SERCA2a at the transcriptional level. Luteolin pretreatment reversed the expression of SERCA2a through the increased expression of Sp1. Moreover, we demonstrated that luteolin pretreatment appeared to exert myocardial protective effects by upregulating the transcriptional activity of SERCA2a, via Sp1. In conclusion, during myocardial ischemia/reperfusion, Sp1 appeared to downregulate the expression of SERCA2a. Luteolin pretreatment was shown to improve SERCA2a expression via the upregulation of Sp1 to attenuate myocardial ischemia/reperfusion injury.

Analysis of chemical components in herbal formula Qi Bai Granule by UPLC-ESI-Q-TOF-MS.

Qi Bai Granule (QBG), a traditional Chinese medicine formula for the treatment of idiopathic thrombocytopenic purpura, is composed of seven herbs. It is necessary to learn its chemical composition for quality control. In this study, a method for rapid separation and structural identification of the constituents in QBG was established by UPLC-ESI-Q-TOF-MS in negative and positive ion mode. As a result, 112 compounds, such as triterpenoids, flavonoids and monoterpenes were detected. Based on the retention times, accurate masses, fragment ions, related literatures, and/or authentic standards, 107 compounds were unambiguously identified or tentatively characterized. Additionally, 20% monarch, 50% minister, 5% assistant and 24% guide drugs of 112 compounds were detected, which on the whole was consistent with the compatibility of QBG. The results would provide a scientific basis for the quality control, quantitative analysis and further study in vivo or vitro of QBG.

m 6A RNA Methylation Decreases Atherosclerotic Vulnerable Plaque Through Inducing T Cells

ABSTRACT Introduction: Knockdown of fat mass and obesity-associated gene (FTO) can induce N6-methyladenosine (m 6A) ribonucleic acid (RNA) methylation. The objective of this study was to explore the effect of m 6A RNA methylation on atherosclerotic vulnerable plaque by FTO knockdown. Methods: A total of 50 New Zealand white rabbits were randomly divided into pure high-fat group, sham operation group, vulnerable plaque group, empty load group, and FTO knockdown group (10 rabbits/group). Results: Flow cytometry showed that helper T (Th) cells in the FTO knockdown group accounted for a significantly higher proportion of lymphocytes than in the vulnerable plaque group and empty load group (P<0.05). Th cells were screened by cell flow. The level of m 6A RNA methylation in the FTO knockdown group was significantly higher than in the vulnerable plaque group and empty load group (P<0.05). The levels of total cholesterol, triglyceride, and low-density lipoprotein C were higher at the 12th week than at the 1st week, but the high-density lipoprotein C level was lower at the 12th week than at the 1st week. At the 12th week, the interleukin-7 level was significantly lower in the adeno-associated virus-9 (AVV9)-FTO short hairpin RNA group than in the control and AVV9-green fluorescent protein groups (P<0.001). Conclusion: After successfully establishing a vascular parkinsonism rabbit model, m 6A RNA methylation can decrease Th cells and vulnerable atherosclerotic plaques.