MATERIALS AND METHODS: BCR-ABL positive CML cells resistant to imatinib (K562-R) were developed by overexposure of K562 cell lines to the drug. Cytotoxicity was determined by MTS assays and IC50 values calculated. Apoptosis assays were performed using annexin V-FITC binding assays and analyzed by flow cytometry. Methylation profiles were investigated using methylation specific PCR and sequencing analysis of SOCS-1 and SOCS-3 genes. Gene expression was assessed by quantitative real-time PCR, and protein expression and phosphorylation of STAT1, 2 and 3 were examined by Western blotting.
RESULTS: The IC50 for imatinib on K562 was 362 nM compared to 3,952 nM for K562-R (p=0.001). Percentage of apoptotic cells in K562 increased upto 50% by increasing the concentration of imatinib, in contrast to only 20% in K562-R (p<0.001). A change from non-methylation of the SOCS-3 gene in K562 to complete methylation in K562-R was observed. Gene expression revealed down- regulation of both SOCS-1 and SOCS-3 genes in resistant cells. STAT3 was phosphorylated in K562-R but not K562.
CONCLUSIONS: Development of cells resistant to imatinib is feasible by overexposure of the drug to the cells. Activation of STAT3 protein leads to uncontrolled cell proliferation in imatinib resistant BCR-ABL due to DNA methylation of the SOCS-3 gene. Thus SOCS-3 provides a suitable candidate for mechanisms underlying the development of imatinib resistant in CML patients.
MATERIALS AND METHODS: Two leukemic cell lines, MV4-11 (acute myeloid leukemia) and K562 (chronic myeloid leukemia), were studied. IC50 concentrations were determined and apoptosis and cell cycle regulation were studied by flow cytometric analysis. The expression of apoptosis and cell-cycle related regulatory proteins was assessed by Western blotting.
RESULTS: P sacharosa inhibited growth of MV4-11 and K562 cells in a dose-dependent manner. The mode of cell death was via induction of intrinsic apoptotic pathways and cell cycle arrest. There was profound up-regulation of cytochrome c, caspases, p21 and p53 expression and repression of Akt and Bcl-2 expression in treated cells.
CONCLUSIONS: These results suggest that P sacharosa induces leukemic cell death via apoptosis induction and changes in cell cycle checkpoint, thus deserves further study for anti-leukemic potential.
METHODS: A cross-sectional survey was conducted in a Malaysian supermarket. Information on sodium, potassium, and phosphorus contents was collected from the nutrition fact panel, while information on food additives containing sodium, potassium, and phosphorus was collected from the ingredient list.
RESULTS: The survey included 2,577 foods and beverages, and 79.4% of the products included sodium information in nutrition fact panels, but only 11.7% and 2.0% disclosed potassium and phosphorus content, respectively. Sodium-containing additives were found in 78.6% of products; potassium- and phosphorus-containing additives were reported in 28.5% and 46.9% of products, respectively. Sodium-containing additives were typically listed as "salt," potassium-containing additives as "alternative names," and phosphorus-containing additives as "starch" and "E numbers." Imported products were more likely to include sodium (P
METHODS: A cross-sectional study was conducted across four health clinics from February 2022 to May 2022. As part of the study, self-administered questionnaires were completed to determine symptoms related to SBS. An indoor air quality (IAQ) assessment was conducted four times daily for fifteen minutes at five areas in each clinic (laboratory, lobby, emergency room, pharmacy, and examination room).
RESULT: Most of the areas illustrated poor air movement (<0.15 m/s), except for the laboratory. The total bacterial count (TBC) was above the standard limit in both the lobby and emergency room (>500 CFU/m3). The prevalence of SBS was 24.84% (77) among the healthcare workers at the health clinics. A significant association with SBS was noted for those working in the examination room (COR = 2.86; 95% CI = 1.31; 6.27) and those experiencing high temperature sometimes (COR = 0.25; 95% CI = 0.11; 0.55), varying temperature sometimes (COR = 0.31; 95% CI = 0.003), stuffy air sometimes (COR = 0.17; 95% CI = 0.005; 0.64), dry air sometimes (COR = 0.20; 95% CI = 0.007; 0.64), and dust sometimes (COR = 0.25; 95% CI = 0.11; 0.60) and everyday (COR = 0.34; 95% CI = 0.14; 0.81). Only healthcare workers in the examination room (AOR = 3.17; 95% CI = 1.35; 7.41) were found to have a significant risk of SBS when controlling for other variables.
CONCLUSION: SBS is prevalent among healthcare workers at health clinics.