Bioinformatics-Led Identification of Potential Biomarkers and Inflammatory Infiltrates in Burn Injury.

Burn injury is a life-threatening disease with a poor prognosis. The immune change and underlying mechanisms remain largely unknown. Thus, this study aims to find potential biomarkers and analyze the immune infiltrates after burn injury. Gene expression data of burn patients were obtained from the Gene Expression Omnibus database. Key immune-related genes (IRGs) were screened by differential and least absolute shrinkage and selection operator (LASSO) regression analysis. Based on key IRGs, patients were divided into two clusters by consensus cluster analysis. Immune infiltration was analyzed by the single sample gene set enrichment analysis (GSEA) method and the immune score was calculated by the principal component analysis method. A nomogram model was constructed based on the calculated immune score and clinical features. Finally, the expression of screened key genes was validated by an external cohort and quantitative polymerase chain reaction experiment. Fifty-nine IRGs were differently expressed in burn patients. After LASSO regression analysis, 12 key genes remained, namely AZU1, OLR1, RNASE2, FGF13, NR1D2, NR2E1, TLR5, CAMP, DEFA4, PGLYRP1, CTSG, and CCR3. Then, patients were divided into two clusters. Immune infiltration analysis revealed that more immune cells were infiltrated and more pathways were activated in cluster A, in which patients showed high immune scores. Finally, a nomogram model was constructed and showed high accuracy and reliability. The expression pattern of 12 key genes in an external cohort and clinical samples was in accordance with the theoretical analysis results. In conclusion, this research elucidated the key role of immune response in burns and could be used as a guide for burn treatment.

Advances in the study of nicotinamide adenine dinucleotide phosphate oxidase in myocardial remodeling.

Myocardial remodeling is a key pathophysiological basis of heart failure, which seriously threatens human health and causes a severe economic burden worldwide. During chronic stress, the heart undergoes myocardial remodeling, mainly manifested by cardiomyocyte hypertrophy, apoptosis, interstitial fibrosis, chamber enlargement, and cardiac dysfunction. The NADPH oxidase family (NOXs) are multisubunit transmembrane enzyme complexes involved in the generation of redox signals. Studies have shown that NOXs are highly expressed in the heart and are involved in the pathological development process of myocardial remodeling, which influences the development of heart failure. This review summarizes the progress of research on the pathophysiological processes related to the regulation of myocardial remodeling by NOXs, suggesting that NOXs-dependent regulatory mechanisms of myocardial remodeling are promising new therapeutic targets for the treatment of heart failure.

Interleukin-5 deletion promotes sepsis-induced M1 macrophage differentiation, deteriorates cardiac dysfunction, and exacerbates cardiac injury via the NF-κB p65 pathway in mice.

Inflammation plays a crucial role in sepsis-induced cardiac injury. The purpose of this study was to determine whether interleukin-5 (IL-5) affected lipopolysaccharide (LPS)-induced cardiac injury by regulating the inflammatory response. First, the expression level and source of cardiac IL-5 were examined, and the results showed that LPS treatment and cecal ligation decreased cardiac IL-5 expression in macrophages. In addition, LPS was used to establish a mouse sepsis model, and the effects of IL-5 deletion on cardiac injury, M1 macrophage differentiation and myocardial cell apoptosis were analyzed. The results showed that IL-5 deficiency significantly increased cardiac injury marker expression, worsened cardiac dysfunction, promoted M1 macrophage differentiation and exacerbated myocardial cell apoptosis in LPS-induced septic mice. The nuclear factor-kappa B (NF-κB) p65 pathway was inhibited by JSH-23, and the results showed that treatment with JSH-23 inhibited M1 macrophage differentiation and alleviated cardiac injury in LPS-treated IL-5-knockout mice. Furthermore, the effects of IL-5 deficiency on M1 macrophage differentiation and myocardial cell apoptosis were measured in vitro. The IL-5-mediated promotion of M1 macrophage differentiation was also reversed by S31-201, and the pro-apoptotic effect of IL-5 knockout on macrophage-mediated myocardial cell apoptosis was also reversed by JSH-23. In conclusion, we found that IL-5 knockout may exacerbate sepsis-induced cardiac injury by promoting M1 macrophage differentiation in mice. IL-5 may be a potential target for the clinical prevention of sepsis-related cardiac injury.

Salidroside downregulates microRNA­133a and inhibits endothelial cell apoptosis induced by oxidized low­density lipoprotein.

Vascular endothelial cell apoptosis is regulated by microRNA­133a (miR­133a), which participates in the formation of atherosclerotic (AS) plaques, leading to the development of several cardiovascular diseases. Salidroside (SAL), the main component of Rhodiola, is considered to exert anti­AS effect; however, its mode of action remains unclear. Thus, the present study aimed to determine whether SAL inhibits endothelial cell apoptosis through the miR­133a pathway. Cultured human coronary artery endothelial cells (HCAECs) were exposed to oxidized low­density lipoprotein (ox­LDL). Cell viability and cytotoxicity were monitored by MTT assay. In parallel, the mRNA expression levels of miR­133a and Bcl­xL, and the protein levels of anti­apoptotic Bcl­xL and activated caspase­3 were measured. The apoptotic levels were examined by flow cytometry. Furthermore, the effects of silencing and overexpressing miR­133a on the parameters mentioned above were evaluated. Exposure to ox­LDL induced an increase in the expression of miR­133a, with a concomitant decrease in the level of Bcl­xL in the HCAECs; these effects were reversed by treatment with SAL. Importantly, the effects of SAL were impaired upon the silencing of miR­133a, whereas the overexpression of miR­133a partly restored the effects of SAL. On the whole, the findings of the present study demonstrate that SAL inhibits the ox­LDL­induced upregulation of miR­133a expression, while promoting the expression of Bcl­xL, thereby preventing endothelial cell apoptosis.

New electronic spectra of the HCCl and DCCl A-X vibronic bands.

The dispersed fluorescence spectra following the excitation of several A<--X vibronic bands of HCCl and DCCl at visible wavelengths were successfully acquired in a discharge supersonic free jet expansion using an intensified charge-coupled device detector. The dispersed fluorescence spectra reveal more details of the X(1) A(') state vibrational structure in these molecules than previous reports. Dispersed fluorescence spectra of all four isotopomers (HC(35)Cl, HC(37)Cl, DC(35)Cl, and DC(37)Cl) were obtained. These dispersed fluorescence spectra exhibit the vibrational structures up to approximately 6000 cm(-1) above the zero-point level and determine the vibrational structures of HC(37)Cl and DC(37)Cl. Complete vibrational parameters including fundamental frequencies, anharmonicities, and coupling constants were determined for the HCCl/DCCl X(1) A(') state. Furthermore, perturbations from the background triplet state a(3) A(") and emission to triplet state levels were observed in the spectra. The singlet-triplet energy gap from the zero-point level could be determined to be 2167 cm(-1) (6.20+/-0.05 kcal/mol) in HCCl and to be 2187 cm(-1) (6.25+/-0.05 kcal/mol) in DCCl. Additionally, some of the A<--X excitation spectrum are reported for HCCl and DCCl.