Correlation of High-Grade Osteosarcoma Response to Chemotherapy with Enhanced Tissue Immunological Response: Analysis of CD95R, IFN-γ, Catalase, Hsp70, and VEGF.

High-grade osteosarcoma, a primary malignant bone tumour, is experiencing a global increase in reported incidence with varied prevalence. Despite advances in management, which include surgery and neoadjuvant chemotherapy often an unsatisfactory outcome is found due to poor or heterogeneous response to chemotherapy. Our study delved into chemotherapy responses in osteosarcoma patients and associated molecular expressions, focusing on CD95 receptor (CD95R), interferon (IFN)-γ, catalase, heat-shock protein (Hsp)70, and vascular endothelial growth factor (VEGF). Employing immunohistochemistry and Huvos grading of post-chemo specimens, we analysed formalin-fixed paraffin-embedded (FFPE) osteosarcoma tissue of resected post-chemotherapy specimens from Dr. Soetomo General Academic Hospital in Surabaya, Indonesia (DSGAH), spanning from 2016 to 2020. Results revealed varied responses (poor 40.38%, moderate 48.08%, good 11.54%) and distinct patterns in CD95R, IFN-γ, catalase, Hsp70, and VEGF expression. Significant differences among response groups were observed in CD95R and IFN-γ expression in tumour-infiltrating lymphocytes. The trend of diminishing CD95R expression from poor to good responses, accompanied by an increase in IFN-γ, implied a reduction in the count of viable osteosarcoma cells with the progression of Huvos grading. Catalase expression in osteosarcoma cells was consistently elevated in the poor response group, while Hsp70 expression was highest. VEGF expression in macrophages was significantly higher in the good response group. In conclusion, this study enhances our understanding of immune-chemotherapy interactions in osteosarcoma and identifies potential biomarkers for targeted interventions.

In Vitro Insulin Resistance Model: A Recent Update.

Insulin resistance, which affects insulin-sensitive tissues, including adipose tissues, skeletal muscle, and the liver, is the central pathophysiological mechanism underlying type 2 diabetes progression. Decreased glucose uptake in insulin-sensitive tissues disrupts insulin signaling pathways, particularly the PI3K/Akt pathway. An in vitro model is appropriate for studying the cellular and molecular mechanisms underlying insulin resistance because it is easy to maintain and the results can be easily reproduced. The application of cell-based models for exploring the pathogenesis of diabetes and insulin resistance as well as for developing drugs for these conditions is well known. However, a comprehensive review of in vitro insulin resistance models is lacking. Therefore, this review was conducted to provide a comprehensive overview and summary of the latest in vitro insulin resistance models, particularly 3T3-L1 (preadipocyte), C2C12 (skeletal muscle), and HepG2 (liver) cell lines induced with palmitic acid, high glucose, or chronic exposure to insulin.

The levels of pro-fibrotic cytokines in pulmonary tuberculosis with minimal and extensive lesions.

BACKGROUND: There are very few studies about the mechanism of fibrosis in tuberculosis (TB). This study aimed to determine the levels of tumor necrosis factor-α (TNF-α), insulin-like growth factor-1 (IGF-1), and transforming growth factor-ß1 (TGF-ß1) in pulmonary TB patients with minimal and extensive lesions. MATERIALS AND METHODS: Cross-sectional observational study design was used to observe the pulmonary TB patients with minimal and extensive lesions, and also healthy controls, each consisting of ten patients. RESULTS: The plasma levels of TNF-α, IGF-1, and TGF-ß1 in pulmonary TB groups were higher compared to the healthy controls. The TNF-α level in the minimal lesion of TB group was higher than the level in the extensive lesion but not significant (P = 0.741). The IGF-1 level in the minimal lesion of TB group was significantly (P = 0.007) increased compared to the extensive lesion. While the TGF-ß1 level in the minimal lesion of TB group was significantly (P = 0.005) lower than the level in the extensive lesion. CONCLUSION: In extensive lesion of TB group, there are differences in the levels of TNF-α, IGF-1, and TGF-ß1 compared to the minimal lesion of TB group as well as the healthy controls. The extent of lesions on chest radiograph also describes the state of ongoing pulmonary fibrosis which can be shown by the differences in the levels of pro-fibrotic cytokines.

The effects of Eucheuma cottonii on alveolar macrophages and malondialdehyde levels in bronchoalveolar lavage fluid in chronically particulate matter 10 coal dust-exposed rats.

OBJECTIVES: To investigate the effect of Eucheuma cottonii on alveolar macrophages (AM) and malondialdehyde (MDA) levels in bronchoalveolar lavage fluids (BALF) in particulate matter 10 (PM10) coal dust-exposed rats. MATERIALS AND METHODS: Ten groups, including a non exposed group and groups exposed to coal dust at doses of 6.25 (CD6.25), 12.5 (CD12.5), or 25 mg/m(3) (CD25) an hour daily for 6 months with or without supplementation of ethanolic extract of E. cottonii at doses of 150 (EC150) or 300 mg/kg BW (EC300). The number of macrophages was determined using a light microscope. MDA levels were measured by TBARS assay. RESULTS: EC150 insignificantly (P > 0.05) reduces the AM in CD groups compared to non treatment groups. EC150 and EC300 significantly (P < 0.05) decreased MDA levels in CD12.5 and CD25 groups relative to non treatment groups. CONCLUSION: E. cottonii attenuated oxidative stress in chronic exposure of PM10 coal dust.

Green tea extract protects endothelial progenitor cells from oxidative insult through reduction of intracellular reactive oxygen species activity.

OBJECTIVES: Many studies have reported that tea consumption decreases cardiovascular risk, but the mechanisms remain unclear. Green tea is known to have potent antioxidant and free radical scavenging activities. This study aimed to investigate whether green tea extract (GTE) can protect endothelial progenitors cells (EPCs) against oxidative stress through antioxidant mechanisms. MATERIALS AND METHODS: Mononuclear cells (MNCs) were isolated from peripheral blood by density gradient centrifugation with Ficoll. The cells were then plated on fibronectin-coated culture dishes. After 7 days of culture, EPCs were characterized as adherent cells double positive for DiI-ac-LDL uptake and lectin binding. EPCs were further identified by assessing the expression of CD34/45, CD133, and KDR. EPCs were then treated with hydrogen peroxide (H2O2) at doses of 50, 100, 200 µM and incubated with or without GTE (25 µg/ml). The intracellular reactive oxygen species (ROS) levels were detected by flow cytometry using a 2',7'-dichlorofluorescein diacetate (DCF-DA) fluorescent probe. RESULTS: GTE ameliorated the cell viability of EPCs induced by H2O2 at doses of 50, 100, 200 µM for about 25.47, 22.52, and 11.96% higher than controls, respectively. GTE also decreased the intracellular ROS levels of EPCs induced by H2O2 at doses of 50, 100, 200 µM for about 84.24, 92.27, and 93.72% compared to controls, respectively. CONCLUSION: GTE improves cell viability by reducing the intracellular ROS accumulation in H2O2-induced EPCs.

The Effects of Eucheuma cottonii on Signaling Pathway Inducing Mucin Synthesis in Rat Lungs Chronically Exposed to Particulate Matter 10 (PM10) Coal Dust.

This study was aimed at investigating the effects of Eucheuma cottonii (EC) in oxidative stress and the signaling for mucin synthesis in rat lungs chronically exposed to coal dust. Coal dust with concomitant oral administration of ethanolic extract of EC at doses of 150 (EC150) or 300 mg/kg BW (EC300) compared to exposed to PM10 coal dust at doses of 6.25 (CD6.25), 12.5 (CD12.5), or 25 mg/m(3) (CD25) (an hour daily for 6 months) and nonexposure group (control). The malondialdehyde (MDA), epidermal growth factor (EGF), transforming growth factor (TGF)- α , epidermal growth factor receptor (EGFR), and MUC5AC levels were determined in the lung. The administration of EC300 significantly (p < 0.05) reduced the MDA levels in groups exposed to all doses of coal dust compared to the respective coal dust-exposed nonsupplemented groups. Although not statistically significant,EC reduced the EGF levels and EGFR expressions in CD12.5 and CD25 groups and decreased the TGF- α , level and MUC5AC expression in CD25 group compared to the respective coal dust-exposed nonsupplemented groups. EC was able to decrease oxidative stress and was also able to decrease signaling for mucin synthesis, at least a part, via reducing the ligand in chronic coal dust exposure.