Sudden cardiac death (SCD) caused by acute ischemic heart disease (IHD) is a major cause of sudden death worldwide. Circular RNAs (circRNAs) are abundant in the heart and play important roles in ...cardiovascular diseases, but the role of circRNAs as biomarkers in the forensic diagnosis of SCD caused by acute IHD remains poorly characterized. To investigate the potential of two heart-enriched circRNAs, circNFIX and circSLC8A1, we explored the expression of these two circRNAs in different kinds of commonly used IHD models, and further verified their expressions in forensic autopsy cases. The results from both the IHD rat and H9c2 cell models revealed that circSlc8a1 level was upregulated, while the circNfix level was elevated in the early stage of ischemia and subsequently downregulated. The time-dependent expression patterns of the two circRNAs suggested their potential as SCD biomarkers. In autopsy cases, the results showed that the expression of these two circRNAs in the myocardium with acute IHD-related SCDs corresponded to the observations in the ischemic models. Further analysis related to myocardial ischemia indicated that circSLC8A1 showed high sensitivity and specificity for myocardial infarction and was positively correlated with creatine kinase MB in pericardial fluid. Downregulated circNFIX level could indicate the ischemic myocardial damage, and it was negatively correlated with the coronary artery stenosis grade. The combination of circSLC8A1 and circNFIX had better performance to discriminate IHD-related SCDs. The results suggested that circSLC8A1 and circNFIX may be used as auxiliary diagnostic markers for SCD caused by acute IHD in forensic medicine.
The prevention and diagnosis of sudden cardiac death (SCD) are among the most important keystones and challenges in clinical and forensic practice. However, the diagnostic value of the current ...biomarkers remains unresolved issues. Therefore, novel diagnostic biomarkers are urgently required to identify patients with early-stage cardiovascular diseases (CVD), and to assist in the postmortem diagnosis of SCD cases without typical cardiac damage. An increasing number of studies show that circular RNAs (circRNAs) have stable expressions in myocardial tissue, and their time- and tissue-specific expression levels might reflect the pathophysiological status of the heart, which makes them potential CVD biomarkers. In this article, we briefly introduced the biogenesis and functional characteristics of circRNAs. Moreover, we described the roles of circRNAs in multiple SCD-related diseases, including coronary artery disease (CAD), myocardial ischemia or infarction, arrhythmia, cardiomyopathy, and myocarditis, and discussed the application prospects and challenges of circRNAs as a novel biomarker in the clinical and forensic diagnosis of SCD.
The FUT3 (Lewis) gene is responsible for the expression of Lewis fucosyltransferase, which is required for the synthesis of the structural determinants of both Lewis
and Lewis
specificity. These ...factors play an important role not only in clinical but also in medico-legal investigations. The gene sequence is highly polymorphic and ethnically specific. In the current study, we performed systematic sequence analysis of the coding region of FUT3 by DNA sequencing to investigate the genetic variations of FUT3 and the molecular basis of the Lewis phenotype in the Sindhi and Punjabi populations of Pakistan. Twenty-three point mutations were observed, including 7 unreported mutations, among which two missense mutations (490 G > A and 959 T > C) were predicted to be deleterious to enzyme activity by software assessment. In total, we observed 24 Lewis alleles, including 11 novel ones. However, all unreported missense mutations were present in Lewis-negative alleles confirmed previously. According to genotypic data, the Lewis-negative phenotypic frequencies were 11.5% and 22.93% in the Sindhi and Punjabi ethnic groups, respectively. Moreover, we found that le
and le
were predominant among Lewis-negative alleles, while the frequency of le
in the Punjabi population was significantly higher than that in the Sindhi population. In summary, our study revealed that there is a relatively high degree of sequence variation of the Lewis gene in Pakistani populations and provided the first genetic data on FUT3 in these two ethnic groups from Pakistan. The allele types and their frequencies showed that these ethnic groups exhibit more Caucasian components.
Chronic alcohol consumption leads to myocardial injury, ventricle dilation, and cardiac dysfunction, which is defined as alcoholic cardiomyopathy (ACM). To explore the induced myocardial injury and ...underlying mechanism of ACM, the Liber-DeCarli liquid diet was used to establish an animal model of ACM and histopathology, echocardiography, molecular biology, and metabolomics were employed. Hematoxylin-eosin and Masson's trichrome staining revealed disordered myocardial structure and local fibrosis in the ACM group. Echocardiography revealed thinning wall and dilation of the left ventricle and decreased cardiac function in the ACM group, with increased serum levels of brain natriuretic peptide (BNP) and expression of myocardial BNP mRNA measured through enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction (PCR), respectively. Through metabolomic analysis of myocardium specimens, 297 differentially expressed metabolites were identified which were involved in KEGG pathways related to the biosynthesis of unsaturated fatty acids, vitamin digestion and absorption, oxidative phosphorylation, pentose phosphate, and purine and pyrimidine metabolism. The present study demonstrated chronic alcohol consumption caused disordered cardiomyocyte structure, thinning and dilation of the left ventricle, and decreased cardiac function. Metabolomic analysis of myocardium specimens and KEGG enrichment analysis further demonstrated that several differentially expressed metabolites and pathways were involved in the ACM group, which suggests potential causes of myocardial injury due to chronic alcohol exposure and provides insight for further research elucidating the underlying mechanisms of ACM.
Evidence on the association between long-term ozone exposure and greenness exposure and hemorrhagic stroke (HS) is limited, with mixed results. One potential source of this inconsistency is the ...difference in exposure time metrics. This study aimed to investigate the association between long-term exposure to ambient ozone, greenness, and mortality from HS using exposure metrics at different times. We also examined whether greenness exposure modified the relationship between ozone exposure and mortality due to HS. The study population consisted of 45771 participants aged ≥40 y residing in 20 counties in Shandong Province who were followed up from 2013 to 2019. Ozone exposure metrics (annual mean and warm season) and the normalized difference a measure of greenness exposure, were calculated. The relationship between environmental exposures (ozone and greenness exposures) and mortality from HS was assessed using time-dependent Cox proportional hazards models, and the modification of greenness exposure was examined using stratified analysis with interaction terms. The person-years at the end of follow-up were 90,663. With full adjustments, the risk of death from hemorrhagic stroke increased by 5% per interquartile range increase in warm season ozone hazard ratio =1.05; 95 % confidence interval: 1.01–1.08. No clear association was observed between annual ozone and mortality HS. Both the annual and summer NDVI were found to reduce the risk of HS mortality. The relationships were influenced by age, sex, and residence (urban or rural). Furthermore, greenness exposure was shown to have a modifying effect on the relationship between ozone exposure and the occurrence of HS mortality (P for interaction = 0.001). Long-term exposure to warm season O3 was positively associated with HS mortality, while greenness exposure was inversely associated with HS mortality. Greenness exposure may mitigate the negative effects of warm season ozone exposure on HS mortality.
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•Warm season ozone positively associated with hemorrhagic stroke (HS) mortality.•Greenness exposure was negatively correlated with HS mortality.•Summer greenness attenuated the adverse effect of ozone on HS mortality.
Chronic alcohol exposure can cause myocardial degenerative diseases, manifested as cardiac insufficiency, arrhythmia, etc. These are defined as alcoholic cardiomyopathy (ACM). Alcohol-mediated ...myocardial injury has previously been studied through metabolomics, and it has been proved to be involved in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway concerning unsaturated fatty acids biosynthesis and oxidative phosphorylation, which tentatively explored the mechanism of ACM induced by chronic drinking. To further study alcohol-induced myocardial injury, myocardial specimens from a previously successfully established mouse model of ACM were subjected to histological, echocardiographic, and proteomic analyses, and validated by real-time quantitative polymerase chain reaction (qPCR). Results of histopathology and echocardiography showed the hypertrophy of cardiomyocytes, the dilation of ventricles, and decreased cardiac function. Proteomic results, available via ProteomeXchange with identifier PXD032949, revealed 56 differentially expressed proteins (DEPs) were identified, which have the potential to be involved in the KEGG pathway related to fatty acid biosynthesis disorders, lipid metabolism disorders, oxidative stress, and, ultimately, in the development of dilated cardiomyopathy (DCM). The present study further elucidates the underlying effects of myocardial injury due to chronic alcohol intake, laying a foundation for further studies to clarify the potential mechanisms of ACM.
Several studies have demonstrated that exercise preconditioning is an effective means of alleviating poststroke cognitive impairment (PSCI). Mechanisms of regulating cognitive function have not been ...fully elucidated. Herein, the present study is aimed at exploring the effect of the microbiota-gut-inflammasome-brain axis in the process of exercise preconditioning moderating cognitive impairment after ischemic stroke. We observed that exercise preconditioning decreased infarct size, reduced the degree of neuronal damage, and alleviated cognitive impairment in mice with ischemic stroke. In addition, exercise preconditioning also reduced the expression of inflammatory cytokines, as well as NLRP3, Caspase-1, IL-18, and IL-1β protein expressions. Ischemic stroke could downregulate the abundance of Roseburia while increasing the abundance of the Helicobacter at the level of genus. As a comparison, exercise preconditioning increased the abundance of the Lactobacillus, which was beneficial for mice at the genus level. In conclusion, exercise preconditioning can improve cognitive dysfunction after ischemic stroke through alleviating inflammation and regulating the composition and diversity of the gut microbiota, which might provide a new strategy for the prevention of PSCI.
Acupuncture and moxibustion are increasingly recognized as effective and safe modalities for the management of neurological disorders, garnering substantial interest from both neurologists and ...patients. This study systematically reviews literature from major databases spanning the years 2012 to 2024 to construct a comprehensive dataset on the acupuncture treatment of neurological diseases. The data were meticulously compiled through a detailed search and screening process, adhering to established principles for data extraction and segmentation. The resultant acupuncture treatment database served as the foundation for subsequent analyses utilizing the association rule algorithm. This advanced computational approach facilitated a deep investigation into the relationships among acupuncture points used in neurological treatments. By employing a complex network analysis, the study identified the optimal distribution of acupuncture points, and cluster analysis further categorized these points for diverse neurological conditions. Our findings indicate that a total of 206 acupuncture points are prevalently used in neurological therapies. The regions of the head, face, and neck are most frequently targeted, with these areas collectively accounting for 1,048 instances of point utilization. Specifically, 124 unique acupuncture points have been identified as particularly effective for neurological applications. The association pairs “Yangbai-Zusanli” and “Sanyinjiao-Zusanli” demonstrated the highest levels of support and confidence, at 96.29% and 48.59% respectively. The core constellation of acupuncture points, comprising “Zhuzhu,” “Yangbai,” “Sizhukong,” “Yuyin,” “Sibai,” “Zusanli,” and “Baihui,” encapsulates the strategic focal areas for enhancing therapeutic outcomes in neurology. The integration of data mining techniques in this research not only underscores the specific patterns in the distribution of acupuncture points but also suggests a potential framework for augmenting the efficacy of treatments for neurological conditions. Through such analytical methodologies, the study contributes to a nuanced understanding of acupuncture’s role in neurology, paving the way for targeted and optimized therapeutic strategies.
Ventricular arrhythmia (VA) is a major component of sudden cardiac death (SCD). To investigate the expression of brain natriuretic peptide (BNP), endothelin-1 (ET-1), and transforming growth ...factor-beta 1 (TGF-β1) during VA, we established a rat model of VA induced by BaCl
solution through a microinjector pump. PD142893 (ET-1 receptor blocker) and SB431542 (TGF-β1 receptor type I blocker) were used to explore the effect of ET-1 and TGF-β1 on BNP expression in the myocardium after VA. BNP, ET-1, and TGF-β1 in rat myocardium were assayed by western blot and immunohistochemical staining for proteins, and real-time quantitative polymerase chain reaction for mRNAs. We found increased expression of BNP and ET-1 in rat myocardium that was associated with the duration of VA. However, TGF-β1 protein expression remained unchanged. Such early increases in BNP and ET-1 may be attributed to fatal arrhythmias associated with SCD, suggesting these may be novel biomarkers of this disease. After intraperitoneal injection of PD142893 and SB431542, respectively, BNP was downregulated in the myocardium of the left ventricle; however, this was abrogated by co-application of the two inhibitors. These results suggested that both ET-1 and TGF-β1, by specifically binding to their receptors, might be involved in the myocardial synthesis of BNP during VA in vivo.
Emissions trading system (ETS) is a cost-effective way towards achieving the carbon neutrality goal. Based on the gaps in the research on carbon allowance allocation vis-à-vis the carbon neutrality ...target, this study examines how to allocate carbon allowances equitably and effectively among Chinese provinces. Different from the previous research that mainly considers responsibility, ability, and potential of equity dimensions, this paper proposes a composite indicator allocation approach based on the equity of history, demand, contribution, and guarantee, and it also employs the entropy method and expert survey method to obtain the indicator weight values in different scenarios. Results show that the carbon allowances of some provinces, such as the forest-rich province of Yunnan, vary significantly in five scenarios, but little differences are observed for some provinces, such as the high historical emissions province of Shanxi. More provinces achieve data envelopment analysis efficiency in the preferred scenario. Compared with the objective scenario, the required emission reduction in the preferred gross domestic product (GDP) scenario is 231 million tonnes less, and the emission reduction cost is 190 billion yuan less. It is suggested that the Chinese government should adopt the allocation scheme in preference for the GDP scenario.
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