Bone cancer is one of the cancer-related diseases, and there are increased numbers of patients with bone cancer worldwide. Therefore the efficacy of treatment of bone cancer is considered extremely vital. Bufalin has been showed to have biological activities including anticancer activities in vitro and in vivo. However, the exact associated mechanisms for bufalin induced apoptosis in human bone cancer cells are still unclear. In the present study, we investigated the effect of bufalin on the cytotoxic effects in U-2 OS human osteosarcoma cells. For examining apoptotic cell deaths, we used flow cytometry assay, Annexin V/PI double staining, and TUNNEL assay. Reactive oxygen species (ROS), Ca²⁺, mitochondrial membrane potential (ΔΨ_m), and caspase-8, -9 and -3 activities were measured by flow cytometry assay. Furthermore, western blotting and a confocal laser microscopy examination were used for measuring the alterations of apoptotic associated protein expression and translocation, respectively. The results indicated that bufalin induced cell morphological changes, decreased the viable cell number, induced apoptotic cell death, and increased the apoptotic cell number, and affected apoptotic associated protein expression in U-2 OS cells. Bufalin increased apoptotic proteins such as Bak, and decreased anti-apoptotic proteins such as Bcl-2 and Bcl-x in U-2 OS cells. Furthermore, bufalin increased the protein levels of cytochrome c (Cyto c), AIF (Apoptosis inducing factor) and Endo G (Endonuclease G) in cytoplasm that were also confirmed by confocal microscopy examination. Based on those findings, bufalin induced apoptotic cell death in U-2 OS cells may be via endoplasmic reticulum (ER) stress, caspase-, and mitochondria-dependent pathways; thus, we may suggest that bufalin could be used as an anti-cancer agent for the treatment of osteosarcoma in the future, and further in vivo studies are needed.

Background: Lethal toxin (LT) is a major virulence factor of Bacillus anthracis. Sprague Dawley rats manifest pronounced lung edema and shock after LT treatments, resulting in high mortality. The heart failure that is induced by LT has been suggested to be a principal mechanism of lung edema and mortality in rodents. Since LT-induced death occurs more rapidly in rats than in mice, suggesting that other mechanisms in addition to the heart dysfunction may be contributed to the fast progression of LT-induced pathogenesis in rats. Coagulopathy may contribute to circulatory failure and lung injury. However, the effect of LT on coagulation-induced lung dysfunction is unclear. Methods: To investigate the involvement of coagulopathy in LT-mediated pathogenesis, the mortality, lung histology and coagulant levels of LT-treated rats were examined. The effects of activated protein C (aPC) on LT-mediated pathogenesis were also evaluated. Results: Fibrin depositions were detected in the lungs of LT-treated rats, indicating that coagulation was activated. Increased levels of plasma D-dimer and thrombomodulin, and the ameliorative effect of aPC further suggested that the activation of coagulation-fibrinolysis pathways plays a role in LT-mediated pathogenesis in rats. Reduced mortality was associated with decreased plasma levels of D-dimer and thrombomodulin following aPC treatments in rats with LT-mediated pathogenesis. Conclusions: These findings suggest that the activation of coagulation in lung tissue contributes to mortality in LT-mediated pathogenesis in rats. In addition, anticoagulant aPC may help to develop a feasible therapeutic strategy.

Obesity is closely associated with metabolic syndrome, type 2 diabetes mellitus (T2DM) and cardiovascular diseases. Our previous reports uncover the significant associations betweeninterleukin-4 (IL-4)/IL-4 receptorgenotypes and T2DM, as well asIL-4genotypes and high density lipoprotein-cholesterol. Theses observations suggest that IL-4 harbors the capacity to regulate lipid metabolism. The present study is aimed at further elucidating regulatory roles of IL-4 to lipid metabolism by identifying putative proteins in 3T3-L1 adipocytes which are differentially expressed under IL-4 treatment. Proteins in mature 3T3-L1 adipocytes with altered expression levels under IL-4 treatment were identified by proteomic strategy. Our results revealed that IL-4 up-regulated levels of ATP synthase δ chain, Cytochromecreductase, Pyrophsphatase and Vimentin, whereas, Alpha-enolase, Gelsolin, Vinculin and Valosin were down-regulated. These observations suggest that IL-4 promotes energy metabolism and inhibit lipid deposits in adipocytes by up-regulating proteins accelerating ATP synthesis. Our results suggest that IL-4 facilitates adipocytes metabolism to catabolism with a favorable condition for lipolysis. These catabolized lipids in adipocytes triggered by IL-4 might either be released into periphery or metabolized intracellularlly, and modulate systemic energy metabolism.

Background/Aim: Casticin, one of the active components of Vitex rotundifolia L., presents biological and pharmacological activities including inhibition of migration, invasion and induction of apoptosis in numerous human cancer cells in vitro. This study aimed to assess the effects of casticin on tumor growth in a human oral cancer SCC-4 cell xenograft mouse model in vivo. Materials and Methods: Twenty-four nude mice were injected subcutaneously with SCC-4 cells and when palpable tumors reached a volume of 100-120 mm³ the mice were randomly divided into three groups. The control (0.1% dimethyl sulfoxide), casticin (0.2 mg/kg), and casticin (0.4 mg/kg) groups were intraperitoneally injected every two days for 18 days. Tumor volume and body weights were measured every two days. Results: Casticin significantly decreased tumor volume and weight in SCC-4 cell xenograft mice but there was no statistically significant difference between the body weights of control mice and mice treated with 0.2 mg/kg or 0.4 mg/kg casticin. Therefore, the growth of SCC-4 cells in athymic nude mice can be inhibited by casticin in vivo. Conclusion: These findings support further investigations in the potential use of casticin as an oral anti-cancer drug in the future.

The use of peritoneal dialysis in end-stage renal disease is increasing in clinical practice. The main purpose of this study was to evaluate the effect of far-infrared radiation therapy on inflammation and the cellular immunity of patients undergoing peritoneal dialysis. We recruited 56 patients undergoing peritoneal dialysis, and we included 32 patients for the experimental group and 24 patients from the control group in the final analysis. The experimental evaluation in our study was as follows: (1) We used abdominal computed tomography to explore the changes in abdominal blood vessels. (2) We compared the effects of peritoneal dialysis using blood glucose, HbAlC, albumin, urea nitrogen, creatinine, white blood cells, hs-CRP; peritoneal Kt/V of peritoneal function, and eGFR. (3) We compared the cytokines’ concentrations in the two groups while controlling for the other cytokines. Results and Discussion: (1) There was no significant difference in the abdominal blood vessels of the experimental group relative to the control group according to abdominal CT over the 6 months. (2) Our study demonstrates statistically significant effects of FIR therapy on the following parameters: creatinine (p = 0.039 *) and hs-CRP (p < 0.001 **) levels decreased significantly, and eGFR (p = 0.043 *), glucose (p < 0.001 **), and albumin (p = 0.048 *) levels increased significantly. Our study found that in the experimental group, creatinine and hs-CRP levels decreased significantly due to FIR therapy for 6 months. However, our study also found that the glucose level was significantly different after FIR therapy for 6 months. Peritoneal dialysis combined with FIR can reduce the side effects of the glucose in the dialysis buffer, which interferes with peritoneal inflammation and peritoneal mesothelial cell fibrosis. (3) In addition, we also found that no statistically significant difference in any inflammatory cytokine after FIR therapy. IFN-γ (p = 0.124), IL-12p70 (p = 0.093), IL-18 (p = 0.213), and TNF-α (p = 0.254) did not exhibit significant improvements after peritoneal dialysis with FIR treatment over 6 months. Conclusions: We found that the effectiveness of peritoneal dialysis was improved significantly with FIR therapy, and significant improvements in the peritoneal permeability and inflammatory response were observed.

Background: Lung cancer continues to be one of the most fatal malignancies globally. Uncovering differentially expressed genes (DEGs) is crucial for advancing our understanding of tumor mechanisms and discovering new therapeutic targets. This study sought to identify key genes linked to prognosis and immune infiltration in lung cancer through the analysis of public gene expression datasets. Methods: We examined three microarray datasets from the Gene Expression Omnibus (GSE10072, GSE33356, and GSE18842) to detect DEGs between tumor and normal lung tissues. Functional enrichment was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses to interpret the biological relevance of these genes. Protein–protein interaction (PPI) networks were constructed via STRING and visualized using Cytoscape to screen for central hub genes. The prognostic implications of the hub genes were investigated using Kaplan–Meier Plotter and TIMER2.0 based on data from The Cancer Genome Atlas (TCGA). PECAM1 expression levels and its relationship with immune cell infiltration were further explored using UCSC Xena. Results: A total of 477 DEGs were consistently identified across all three datasets. Among the top 10 down-regulated hub genes, PECAM1 was significantly reduced in tumor tissues. Lower PECAM1 expression was positively associated with better first-progression survival (FPS) in lung cancer patients. This gene was particularly suppressed in lung adenocarcinoma (LUAD) and showed strong correlations with immune cell infiltration. Co-expression analysis revealed that genes linked to PECAM1 are involved in immune-related pathways. Conclusions: Our findings highlight PECAM1 as a potential prognostic biomarker in lung cancer, especially in LUAD. Its association with immune infiltration and patient survival supports its possible utility in early detection and as a candidate for immunotherapy development.