Sulfur Dioxide Alleviates Organ Damage and Inflammatory Response in Cecal Ligation and Puncture-Induced Sepsis Rat.

The study aimed to elucidate the mechanisms by which sulfur dioxide (SO2) alleviates organ damage during sepsis using RNA-Seq technology. A cecal ligation and puncture (CLP) sepsis model was established in rats, and the effects of SO2 treatment on organ damage were assessed through histopathological examinations. RNA-Seq was performed to analyze differentially expressed genes (DEGs), and subsequent functional annotations and enrichment analyses were conducted. The CLP model successfully induced sepsis symptoms in rats. Histopathological evaluation revealed that SO2 treatment considerably reduced tissue damage across the heart, kidney, liver, and lungs. RNA-Seq identified 950 DEGs between treated and untreated groups, with significant enrichment in genes associated with ribosomal and translational activities, amino acid metabolism, and PI3K-Akt signaling. Furthermore, gene set enrichment analysis (GSEA) showcased enrichments in pathways related to transcriptional regulation, cellular migration, proliferation, and calcium-ion binding. In conclusion, SO2 effectively mitigates multi-organ damage induced by CLP sepsis, potentially through modulating gene expression patterns related to critical biological processes and signaling pathways. These findings highlight the therapeutic promise of SO2 in managing sepsis-induced organ damage.

Association Between IL-17 and Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

Background: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by neutrophils airway infiltration. It is currently known that Interleukin-17 (IL-17) is an important pro-inflammatory factor. It can promote the accumulation of neutrophils and participate in the chronic inflammatory process of COPD. However, the value of IL-17 levels in the diagnosis and assessment of COPD remains controversial. In view of this, we conducted a systematic review and meta-analysis to assess its relevance. Methods: We searched databases such as PubMed, Web of Science, Cochrane Library and Embase to extract original research. Results: A total of 10 studies with 2268 participants were included in this meta-analysis. The results showed that the level of serum IL-17 in patients with stable COPD was significantly higher than that in healthy controls (standard mean difference SMD, 1.59, 95% CI 0.84-2.34; p<0.001). Compared with the stable COPD group, the serum IL-17 level in acute exacerbation (AECOPD) was significantly higher (SMD, 1.78, 95% CI 1.22-2.33; p<0.001). The level of IL-17 in sputum of COPD patients was also higher than that of healthy controls (SMD, 2.03, 95% CI 0.74-3.31; p<0.001). Conclusion: Our results showed that IL-17 levels were elevated in serum and sputum in COPD patients compared with healthy controls, and IL-17 levels increased with disease progression. IL-17 serves as a potential biomarker to indicate the persistence of neutrophilic inflammation and exacerbation of COPD.

Role of Th17 cells, Treg cells, and Th17/Treg imbalance in immune homeostasis disorders in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, following strokes and cardiovascular diseases. Chronic lung inflammation is believed to play a role in the development of COPD. In addition, accumulating evidence shows that the immune system plays a crucial role in the pathogenesis of COPD. Significant advancements have been made in research on the pathogenesis of immune diseases and chronic inflammation in recent years, and T helper 17 (Th17) cells and regulatory T (Treg) cells have been found to play a crucial role in the autoimmune response. Th17 cells are a proinflammatory subpopulation that causes autoimmune disease and tissue damage. Treg cells, on the other hand, have a negative effect but can contribute to the occurrence of the same disease when their antagonism fails. This review mainly summarizes the biological characteristics of Th17 cells and Treg cells, their roles in chronic inflammatory diseases of COPD, and the role of the Th17/Treg ratio in the onset, development, and outcome of inflammatory disorders, as well as recent advancements in immunomodulatory treatment targeting Th17/Treg cells in COPD.

Metformin reverses the resistance mechanism of lung adenocarcinoma cells that knocks down the Nrf2 gene.

The nuclear factor, erythroid 2 like 2 (Nrf2)/antioxidant response element (ARE) pathway has an important role in the drug resistance of adenocarcinoma, and may act via different mechanisms, including the mitogen-activated protein kinase (MAPK) pathway. However, it has remained elusive whether metformin affects Nrf2 and regulates Nrf2/ARE in adenocarcinoma. In the present study, reverse-transcription quantitative polymerase chain reaction, cell transfection, western blot analysis, a Cell Counting kit-8 assay and apoptosis detection were used to investigate the above in the A549 cell line and cisplatin-resistant A549 cells (A549/DDP). The results indicated that Nrf2, glutathione S-transferase α 1 (GSTA1) and ATP-binding cassette subfamily C member 1 (ABCC1) were dose-dependently reduced by metformin, and that the effect in A549 cells was greater than that in A549/DDP cells. Treatment with metformin decreased the proliferation and increased the apoptosis of A549 cells to a greater extent than that of A549/DDP cells, and the effect was dose-dependent. After transfection of A549/DDP cells with Nrf2 short hairpin RNA (shRNA), GSTA1 and ABCC1 were markedly decreased, compared with the shRNA-control group of A549/DDP, and low dose-metformin reduced the proliferation and increased apoptosis of A549/DDP cells. Metformin inhibited the Akt and extracellular signal-regulated kinase (ERK)1/2 pathways in A549 cells and activated the p38 MAPK and c-Jun N-terminal kinase (JNK) pathways. Furthermore, in the presence of metformin, inhibitors of the p38 MAPK and JNK signaling pathway at different concentrations did not affect the levels of Nrf2, but inhibitors of the Akt and ERK1/2 pathway at different doses reduced the expression of Nrf2. In addition, inhibitors of p38 MAPK and JNK did not affect the effect of metformin on Nrf2, while inhibitors of Akt and ERK1/2 dose-dependently enhanced the inhibitory effects of metformin in A549 cells. In conclusion, metformin inhibits the phosphoinositide-3 kinase/Akt and ERK1/2 signaling pathways in A549 cells to reduce the expression of Nrf2, GSTA1 and ABCC1. Metformin also reverses the resistance of A549/DDP cells to platinum drugs, inhibits the proliferation and promotes apoptosis of drug-resistant cells. These results may provide a theoretical basis and therapeutic targets for the clinical treatment of tumors.

Vitamin D3 repressed astrocyte activation following lipopolysaccharide stimulation in vitro and in neonatal rats.

Vitamin D3 has been reported to be an immunity modulator and high levels of vitamin D3 are correlated with a decreased risk for developing diseases in the central nervous system. Astrocytes are important immune cells and contribute toward inflammation during neurological diseases. The vitamin D receptor has been reported to be expressed in astrocytes; however, the effect of vitamin D3 on astrocyte activation has not been studied. Here, we found that lipopolysaccharide stimulation in astrocytes could enhance the expression of vitamin D receptor and Cyp27B1, which encodes the enzyme for converting vitamin D3 into its active form. Vitamin D3 suppressed the expression of proinflammatory cytokines tumour necrosis factor-α, interleukin-1ß, vascular endothelial growth factor, and also TLR4 in activated astrocytes. Astrocyte activation was further found to be suppressed after the administration of vitamin D3 in neonatal rats injected with lipopolysaccharide in vivo. We demonstrated the antiactivation effect of vitamin D3 in astrocytes after lipopolysaccharide stimulation. Considering the function of reactive astrocytes in augmenting inflammatory response in neurodegeneration and brain injury, the finding that vitamin D3 administration may inhibit astrocyte activation may be potentially useful for the treatment of central nervous system disorders.

Genetic effects of XRCC4 and ligase IV genes on human glioma.

Ligase IV and XRCC4 genes, important molecules in the nonhomologous end-joining pathway for repairing DNA double-strand breaks, may play crucial roles in carcinogenesis. To detect their effects on the risk of human glioma, their gene expression differences between 110 human glioma tissues and 50 healthy brain tissues were determined using quantitative real-time PCR. Furthermore, two tagging single nucleotide polymorphisms (SNPs) in ligase IV and four SNPs in XRCC4 genes were genotyped in 317 glioma patients and 352 healthy controls. The association of glioma and ligase IV/XRCC4 was evaluated using methods for SNP, haplotype, and gene-gene interaction analysis. Compared with those in normal brain tissues, the relative gene expression levels of ligase IV and XRCC4 were significantly downregulated in glioma tissue (P=0.0017 and 0.0006, respectively). Single SNP analysis indicated that only rs10131 in ligase IV remained significantly associated with glioma (P=0.0036) after 10 000 permutation tests. Haplotype analysis showed that the haplotype profiles of ligase IV and XRCC4 were significantly different between glioma patients and healthy controls (P=0.004 and 3.13E-6, respectively). Finally, the gene-gene interaction analysis suggested that the three-locus model (rs1805388, rs10131, and rs2075685) was the best model for ligase IV and XRCC4 to have interaction effects on the risk of glioma. In conclusion, both ligase IV and XRCC4 may act in concert to modulate the development of glioma.