Diabetes mellitus, a life-threatening non-communicable disease, is now an epidemic-level problem in developed countries, and also prevalent in developing countries, including Bangladesh. Bangladesh ...has been facing a significant and growing burden of diabetes mellitus handling in recent decades. In the present study, we investigated whether a daily walking intervention could improve the fasting blood sugar level in newly diagnosed diabetes mellitus participants in rural Bangladesh who were not on medication. A rural population of 1,045 people in Bangladesh were screened for diabetes mellitus. One hundred fifty-six people, including 87 diabetes mellitus participants, went through a 5-month daily walking program (twice daily, 1.5 km walking each time). In our initial screening, the prevalence of newly diagnosed diabetes mellitus cases was 8.5% in the rural population. Mean fasting blood sugar level in these new diabetes mellitus cases was 10.0 ± 0.33 mmol/L. After five months of exercise, both the fasting blood sugar and 2h OGTT sugar levels were significantly improved, and no DM (diabetes mellitus) cases were on medication. The current research findings show that a walking program can be a potential lifestyle intervention to combat the diabetes mellitus epidemic in a poor rural context in Bangladesh.
Parity increases the risk for coronary heart disease; however, its association with metabolic syndrome among women in low-income countries is still unknown.
This study investigates the association ...between parity or gravidity and metabolic syndrome in rural Bangladeshi women.
A cross-sectional study was conducted in 1,219 women aged 15-75 years from rural Bangladesh. Metabolic syndrome was defined according to the standard NCEP-ATP III criteria. Logistic regression was used to estimate the association between parity and gravidity and metabolic syndrome, with adjustment of potential confounding variables.
Subjects with the highest gravidity (> = 4) had 1.66 times higher odds of having metabolic syndrome compared to those in the lowest gravidity (0-1) (P trend = 0.02). A similar association was found between parity and metabolic syndrome (P(trend) = 0.04), i.e., subjects in the highest parity (> = 4) had 1.65 times higher odds of having metabolic syndrome compared to those in the lowest parity (0-1). This positive association of parity and gravidity with metabolic syndrome was confined to pre-menopausal women (P(trend) <0.01). Among the components of metabolic syndrome only high blood pressure showed positive association with parity and gravidity (P(trend) = 0.01 and <0.001). Neither Parity nor gravidity was appreciably associated with other components of metabolic syndrome.
Multi parity or gravidity may be a risk factor for metabolic syndrome.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Protein-tyrosine phosphorylation is one of the posttranslational modifications and plays critical roles in regulating a wide variety of cellular processes, such as cell proliferation, ...differentiation, adhesion, migration, survival, and apoptosis. Protein-tyrosine phosphorylation is reversibly regulated by protein-tyrosine kinases and protein-tyrosine phosphatases. Strong inhibition of protein-tyrosine phosphatase activities is required to undoubtedly detect tyrosine phosphorylation. Our extremely careful usage of Na3VO4, a potent protein-tyrosine phosphatase inhibitor, has revealed not only the different intracellular trafficking pathways of Src-family tyrosine kinase members but also novel tyrosine phosphorylation signals in the nucleus and on mitotic spindle fibers and lysosomes. Furthermore, despite that the first identified oncogene product v-Src is generally believed to induce transformation through continuous stimulation of proliferation signaling by its strong tyrosine kinase activity, v-Src-driven transformation was found to be caused not by continuous proliferation signaling but by v-Src tyrosine kinase activity-dependent stochastic genome alterations. Here, I summarize our findings regarding novel tyrosine phosphorylation signaling in a spatiotemporal sense and highlight the significance of the roles of tyrosine phosphorylation in transcriptional regulation inside the nucleus and chromosome dynamics.
Src family non-receptor-type tyrosine kinases regulate a wide variety of cellular events including cell cycle progression in G2/M phase. Here, we show that Src signaling regulates the terminal step ...in cytokinesis called abscission in HeLa cells. Abscission failure with an unusually elongated intercellular bridge containing the midbody is induced by treatment with the chemical Src inhibitors PP2 and SU6656 or expression of membrane-anchored Csk chimeras. By anti-phosphotyrosine immunofluorescence and live cell imaging, completion of abscission requires Src-mediated tyrosine phosphorylation during early stages of mitosis (before cleavage furrow formation), which is subsequently delivered to the midbody through Rab11-driven vesicle transport. Treatment with U0126, a MEK inhibitor, decreases tyrosine phosphorylation levels at the midbody, leading to abscission failure. Activated ERK by MEK-catalyzed dual phosphorylation on threonine and tyrosine residues in the TEY sequence, which is strongly detected by anti-phosphotyrosine antibody, is transported to the midbody in a Rab11-dependent manner. Src kinase activity during the early mitosis mediates ERK activation in late cytokinesis, indicating that Src-mediated signaling for abscission is spatially and temporally transmitted. Thus, these results suggest that recruitment of activated ERK, which is phosphorylated by MEK downstream of Src kinases, to the midbody plays an important role in completion of abscission.
Non-communicable disease (NCD) is now a burning public health issue in Bangladesh. Among crucial NCD risk factors, widespread low high-density lipoprotein cholesterol (HDL-C) levels is of top concern ...in Bangladesh. Over the last ten years, through an extensive nationwide investigation in Bangladesh, we found that more than 80% apparently healthy rural women in Bangladesh have low HDL-C levels. Thus, the present study investigated whether a lifestyle intervention program through daily walking could improve the low HDL-C levels in these women. A total of 231 rural women in Bangladesh were studied using an interventional approach, and analysis was performed based on a case-control design between low HDL-C and normal HDL-C. The subjects underwent a ten-week daily walking program (1.5 km walk twice a day). Among 231 participants at baseline, those with low HDL-C levels were 82.5%. Mean total HDL-C levels were 39.4 mg/dl in low HDL-C subjects and 56.1 mg/dl in normal HDL-C subjects, respectively, at baseline levels. The percentage of hypertriglyceridemia was 25.5% in low, and 10.3% in normal HDL-C subjects and the percentage of diabetes mellitus was 16.4% in low and 7.7% in normal HDL-C subjects before the exercise intervention. Although blood glucose levels and blood pressure were not changed significantly after the exercise intervention, low HDL-C levels were significantly improved with exercise (baseline, 39.8 ± 0.56; exercised, 46.3 ± 1.01, p < 0.001). The current research findings show that even a 10-week mild exercise program improved low HDL-C levels in rural Bangladeshi women, which can be a potential strategy for the prevention of NCD.
The ErbB family of receptor tyrosine kinases comprises four members: epidermal growth factor receptor (EGFR)/ErbB1, HER2/ErbB2, ErbB3 and ErbB4, and plays roles in signal transduction at the plasma ...membrane upon ligand stimulation. Stimulation with neuregulin-1 (NRG-1) cleaves ErbB4 and releases the ErbB4 intracellular domain (4ICD) that translocates into the nucleus to control gene expression. However, little is known about the regulation of 4ICD nuclear signaling through tyrosine phosphorylation. We show here that 4ICD nuclear signaling is antagonized by EGF-induced c-Src activation through EGFR. Generation of 4ICD by NRG-1 leads to increased levels of trimethylated histone H3 on lysine 9 (H3K9me3) in a manner dependent on the nuclear accumulation of 4ICD and its tyrosine kinase activity. Once EGF activates c-Src downstream of EGFR concomitantly with NRG-1-induced ErbB4 activation, c-Src associates with phospho-Tyr950 and phospho-Tyr1056 on 4ICD, thereby decreasing nuclear accumulation of 4ICD and inhibiting an increase of H3K9me3 levels. Moreover, 4ICD-induced transcriptional repression of the human telomerase reverse transcriptase (hTERT) is inhibited by EGF-EGFR-Src signaling. Thus, our findings reveal c-Src-mediated inhibitory regulation of ErbB4 nuclear signaling upon EGFR activation.
•The ZnF7 mutant of A20 failed to suppress TNF-α-induced apoptosis.•In the absence of cIAP1/2, A20 did not suppress TNF-α-induced apoptosis.•A20 was suggested to suppress TNF-α-induced apoptosis ...through controlling cIAP1/2.
The ubiquitin-editing enzyme A20 suppresses nuclear factor-κB (NF-κB) activation and tumor necrosis factor-α (TNF-α)-induced apoptosis in a deubiquitinating and ubiquitin ligase activity-dependent manner. Although recent studies revealed that A20 regulates NF-κB independently of its enzymatic activity through its seventh zinc finger motif (ZnF7), the involvement of ZnF7 in TNF-α-induced apoptosis is not clear. In this study, ZnF7 was found to be important for A20-mediated suppression of TNF-α-induced apoptosis. We also found that the ubiquitin ligases cIAP1/2 are required for A20 to suppress TNF-α-induced apoptosis. Because A20 binds to cIAP1/2 through ZnF7, these results suggest that A20 may control cIAP1/2 when suppressing TNF-α-induced apoptosis.
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