• Multiple miRNAs were significantly differentially expressed in offspring rat hippocampus after fluorine combined with aluminum (FA) exposure. • Twenty differentially expressed miRNAs might mediate FA-induced developmental neurotoxicity. • MiR-10a-5p, miR-34b-5p, and miR-182 were closely related to neurotoxic signaling of FA. • The BDNF-TrkB learning and memory-associated pathway was downregulated in the hippocampus after FA exposure.

This study was aimed at identifying molecular markers associated with the pathogenesis of sudden cardiac death (SCD). It provides a proteomic analysis of human left anterior descending coronary artery from subjects diagnosed with SCD through histological examination and cases of nondisease accidental deaths through autopsy. A total of 2784 proteins were obtained from label-free quantitative proteomic analysis. This included a total of 265 differential proteins which were involved in SCD-related processes, such as inflammation, muscle system process regulation, metal ion transport, and lysosomal pathway. Western blotting was carried out to measure the expressions of cathepsin C (CTSC), focal adhesion kinase (FAK), p-FAK, and proteins related to the p38/MAPK signaling pathway, whereas immunohistochemistry was performed to determine the localization and expression of CTSC, TNF-α, and CD206 in arterial tissues. It was found that CTSC were the most expressed proteins with a significant upward trend in SCD cases. Besides, CTSC regulated macrophage polarization to M1 through the FAK-induced p38/MAPK signaling pathway. This promoted the release of inflammatory factors and eventually increased the inflammatory response. In conclusion, this study implies that CTSC may be one of the key molecular targets for promoting macrophage M1 polarization in SCD, which may provide new therapeutic insights into the treatment of inflammatory diseases.

Background The Cathepsins family, including cathepsin B and cathepsin D, potentially affects the entire processes involved in atherosclerosis. Although coronary heart disease (CHD) has been widely studied as the basis of Sudden Cardiac Death (SCD), the relationship between CHD and CTSB/D remains unclear. Methods We screened for differentially expressed proteins (DEPs) associated with autophagy by limma package in R. For the genes corresponding to the DEPs after screening, we used various databases to carry out functional enrichment of related DEGs to explore their possible influence on a specific aspect of the disease. Functional enrichment analysis of DEGs was performed by DAVID, Metascape and GSEA. STRING and Cytoscape were obtained the hub genes, the analysis of interaction networks through the GENMANIA and Networkanalyst. Western Blot was used to validate the protein expression level of target genes. TF and miRNA prediction were performed using Networkanalyst and visualized using Cytoscape. Results The expression levels of members of the cathepsin family were up regulated in CHD tissues compared with the control. GO and KEGG revealed that cathepsin was markedly enriched in endopeptidase activities, immune responses, lysosome pathways, et al. The correlation analysis showed that in patients with CHD, the CTSB/CTSD expression were negatively correlated with ATG4D and BNIP3, but positively with BCL2L1, CAPNS1, and TP53. In the TF-mRNA-miRNA network, has-miR-24-3p and has-miR-128-3p had higher degrees, CTSB/CTSD could be targeted by them. Conclusions Our findings elucidated the expression and regulatory role of cathepsins in coronary heart disease induced SCD and might further explore the potential mechanisms of autophagy in CHD.

BackgroundCoronary heart disease is related to sudden death caused by multi-factors and a major threat to human health.This study explores the role of OX40L and ICAM-1 in the stability of coronary plaques and their relationship with sudden coronary death.MethodsA total of 118 human coronary arteries with different degrees of atherosclerosis and/or sudden coronary death comprised the experimental group and 28 healthy subjects constituted the control group were isolated from patients. The experimental group was subdivided based on whether the cause of death was sudden coronary death and whether it was accompanied by thrombosis, plaque rupture, plaque outflow and other secondary changes: group I: patients with coronary atherosclerosis but not sudden coronary death, group II: sudden coronary death without any of the secondary changes mentioned above, group III: sudden coronary death with coronary artery atherosclerotic lesions accompanied by either of the above secondary changes. The histological structure of the coronary artery was observed under a light microscope after routine HE staining, and the related indexes of atherosclerotic plaque lesions were assessed by image analysis software. The expressions of OX40L and ICAM-1 were detected by real-time quantitative PCR (RT-PCR), immunohistochemistry (IHC) and Western blotting, and the correlations between the expressions and the stability of coronary atherosclerotic plaque and sudden coronary death were analyzed.Results(1) The expression of OX40L protein in the control group and the three experimental groups showed an increasing trend, and the difference between groups was statistically significant (P < 0.05). (2) The expression of the ICAM-1 protein in the control group and the three experimental groups showed a statistically significant (P < 0.05) increasing trend. (3) The expression of OX40L and ICAM-1 mRNAs increased in the control and the three experimental groups and the difference was statistically significant (P < 0.05).ConclusionThe expression of OX40L and ICAM-1 proteins and mRNAs is positively correlated with the stability of coronary atherosclerotic plaque and sudden coronary death.

BackgroundTraumatic head injury is a leading cause of death and disability worldwide. How clinicopathological features differ by age remains unclear. This epidemiological study analyzed the clinicopathological features of patients with head injury belonging to 3 age groups.Material/MethodsData of patients with traumatic head injury were obtained from the Department of Cerebral Surgery of the Affiliated Hospital of Guizhou Medical University and the Guizhou Provincial People’s Hospital in 2011–2015. Their clinicopathological parameters were assessed. The patients were divided into 3 age groups: elderly (≥65 years), middle-aged (18–64 years), and juvenile (≤17 years) individuals.ResultsAmong 3356 hospitalizations for traumatic head injury (2573 males and 783 females, 654 died (19.49%), the highest and lowest mortality rates were in the elderly and juvenile groups, respectively. Fall was the most common cause in juvenile and elderly individuals (32.79% and 43.95%, respectively), while traffic injury was most common in the elderly group (35.08%). The manners of injury differed considerably among the 3 age groups. Scalp injury, skull fracture, intracranial hematoma, and cerebral injury were the most common mechanisms in juvenile (67.32%), middle-aged (63.50%), elderly (69.56%) and middle-aged (90.44%) individuals, respectively. Scalp injury and skull fracture types differed among the groups. Epidural, subdural, and intracerebral hematomas were most common in juvenile, middle-aged, and elderly individuals, respectively. Cerebral contusion showed the highest frequency in the 3 groups, and concussion the lowest.ConclusionsPatients with traumatic HI show remarkable differences in clinicopathological features among juvenile, middle-aged, and elderly individuals.