河南医学高等专科学校

Ischemic heart disease (IHD) is a major cardiovascular health concern. In addition to metabolic and behavioral risks, diesel particulate matter (DPM), with a widely exposed population, is an important external environmental risk factor for IHD. However, the effect biomarkers used to diagnose DPM-caused IHD and underlying mechanisms remain unknown. We investigated the biomarkers and underlying mechanisms of DPM in relation to myocardial hypoxia injury. This study applied a unique population of diesel engine testers with stable DPM exposure. Electrocardiogram examination, echocardiogram examination, serum levels of myocardial enzymes, and 6-min walking test were used for the myocardial risks assessment. A mouse model exposed to occupational environmental DPM dose and in vitro models of DPM-induced myocardial hypoxia injury were used for assessment of mitochondrial aerobic metabolism via the oxygraph-2k system, western blotting, and kits. Ion fluorescence probes, ion supplements, and mitochondrial RNA splicing protein 2 (Mrs2) overexpression transfection were used in further investigations and verifications of the mechanism of mitochondrial Mg2+ deficiency. We identified compromised myocardial mitochondrial aerobic metabolism as a precursor biomarker for the cardiac risk of myocardial hypertrophy and hypoxia injury in DPM exposure. DPM induce mitochondrial Mg2+ deficiency of cardiomyocytes, which in turn disrupt the mitochondrial aerobic metabolism processes, including the tricarboxylic acid cycle, oxidative phosphorylation, and ATP synthesis. Mg2+ deficiency is mediated by the disruption of Mg2+ transport proteins, such as DPM-enhanced hyperubiquitination and degradation of Mrs2, a protein responsible for mitochondrial Mg2+ uptake. Our findings show that compromised mitochondrial aerobic metabolism, associated with Mg2+ deficiency, serves as a critical biomarker for DPM-induced IHD and represents a promising investigative avenue for intervention.

Central post-stroke pain (CPSP) is a debilitating neuropathic condition that significantly impairs quality of life and is challenging to manage. Salvia miltiorrhiza (Danshen), a traditional Chinese herb, has demonstrated efficacy against neuropathic pain, but its active analgesic components and underlying mechanisms remain unclear. This study investigated the therapeutic potential of Danshenol B, an active component of Danshen, in a CPSP mouse model, focusing on its mechanism of action via the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (PIK3CG)/NLR family pyrin domain-containing protein 3 (NLRP3) signaling pathway. A CPSP model was established in mice, and RNA sequencing of the ipsilateral ventral posterolateral thalamic nucleus/ventral posteromedial thalamic nucleus (VPL/VPM) was performed to identify differentially expressed genes (DEGs). Network pharmacology analysis linked these DEGs to known Danshen components, and molecular docking of 42 Danshen constituents was conducted to identify strong ligand-target interactions. Danshenol B was then administered (5, 10, 50 mg/kg) to CPSP mice to evaluate its analgesic effects, and thalamic PIK3CG and NLRP3 protein levels were measured to assess pathway involvement. Additionally, PIK3CG and NLRP3 expression were manipulated (via overexpression or knockdown) to determine their roles in CPSP and their regulatory relationship. In the CPSP model, 409 DEGs were identified in the ipsilateral VPL/VPM. Network pharmacology revealed 21 Danshen-derived compounds potentially targeting 11 of these DEGs. Molecular docking highlighted Danshenol B as a top candidate, showing strong binding (-9.127 kcal/mol) to PIK3CG. In CPSP mice, Danshenol B (50 mg/kg) significantly alleviated CPSP and suppressed the PIK3CG/NLRP3 pathway. The overexpression of PIK3CG increased NLRP3 and negated the effects of Danshenol B, whereas its knockdown alleviated CPSP and reduced NLRP3. Notably, simultaneous overexpression of NLRP3 attenuated the analgesic effects induced by PIK3CG knockdown, further confirming that NLRP3 functions downstream of PIK3CG in mediating CPSP. Danshenol B alleviates CPSP in mice by suppressing the PIK3CG/NLRP3 signaling pathway, elucidating its analgesic mechanism and highlighting its potential as a novel therapeutic candidate for CPSP.

Diesel exhaust (DE) is a significant contributor to the traffic-related air pollution (TRAP) and has been linked to multiple adverse health outcomes. However, research on glycolipid metabolic disturbance associated with human exposure to DE remains scarce. Based on the cohort of diesel engine testers (DETs), this study revealed that DE exposure could disrupt liver function and interfere with the glucose and lipid metabolism in humans. By combining targeted analyses of amino acids and fatty acids with untargeted lipidomics approaches, we comprehensively elucidated the altered plasma metabolic profiles induced by DE exposure. A total of 8 amino acids, 3 fatty acids, and 36 lipids were identified as differential metabolites. These perturbed metabolites further indicate the impaired glycolipid metabolism, and furnish evidence of the adverse health risks resulting from DE exposure, primarily encompassing insulin resistance, cardiovascular diseases (CVDs), liver diseases, and neurotoxicity. A machine learning-based regression algorithm identified metabolites that are likely to mediate changes in the clinical indicators related to glycolipid metabolism. Mediation analysis and validation cohort showed that alanine (Ala), AcCa(21:1), and PC(38:1) potentially serve as early predictive biomarkers for DE-induced alterations in glucose levels. This study offers the first metabolic evidence establishing a link between DE exposure and glycolipid metabolic disturbance, highlighting the potential health risks posed by TRAP.

Tuberculosis (TB) can easily spread among students and can lead to an outbreak once there is an infection in a school. Outbreaks of drug-resistant TB (DR-TB) in schools have occasionally been reported, but the profile of DR-TB in students in a province has rarely been described. This study was conducted to determine the prevalence of DR-TB and factors associated with it in students in Henan Province, China. We retrospectively reviewed the data of 3527 pulmonary TB patients among students with culture-confirmed Mycobacterium tuberculosis (M.tb) isolates collected from the Tuberculosis Information Management System of the China Disease Prevention and Control Information System from 2015 to 2021. Prevalence of DR-TB was analyzed. Comparisons between categorical variables were analyzed using the chi-square test or Fisher’s exact test as appropriate. Logistic regression models were used to identify the factors associated with DR-TB. Any DR-, RR (rifampin resistance)- and MDR (multi-drug resistance) -TB rates in students were 10.46

Diesel exhaust (DE) entering the environment poses a significant risk to public health, but the molecular mechanisms of DE-induced metabolic disorders remain largely unknown. Here we elucidated the impacts of DE exposure on hepatic lipid metabolism using a range of cohort, in vivo, and in vitro approaches. The cohort study revealed altered liver function indices of diesel engine testers (DETs) compared to those of non-DETs and with increasing exposure duration. Mice exposed to DE via whole-body exposure system developed hepatic steatosis, which coincided with an upregulation of the fatty acid transporter CD36, and a marked increase in long-chain fatty acids. Mechanistically, enhanced CD36 expression was predominantly related to the activation of aryl hydrocarbon receptor (AHR). Notably, treatment with organic extract of diesel exhaust particulate (DEP-OE) up-regulated the AHR/CD36 signaling pathway, and led to lipid accumulation in primary mouse hepatocytes. Both effects were markedly diminished by AHR and CD36 knockdown. Finally, we show that targeted inhibition of AHR alleviated DE-induced steatosis in mouse liver. Together, we demonstrate that the organic components of DE cause hepatic steatosis by activating the AHR/CD36 signaling pathway. Our research elucidates DE exposure risks and sheds new insights into the early prevention of diseases in DE-exposed populations.