Holmthorpe9623

Insulin usage (OR5.44; 95% CI1.53, 19.43; p=0.009), abnormal glycated hemoglobin (OR8.70; 95% CI2.68,26.27; p less then 0.01), hospital follow-up (OR3.38; 95% CI 1.11, 10.34; p=0.033) and neonatal intensive care unit admission (OR3.96; 95% CI 1.16, 13.54; p=0.028) were found to have significant associations with abnormal glucose tolerance at six weeks postpartum. Conclusion The proportion of women with a history of GDM and abnormal glucose tolerance at six weeks postpartum in Johor Bahru was 12% and was associated with insulin usage, abnormal glycated hemoglobin, hospital follow-up and neonatal intensive care unit admission. Screening during the postpartum period offers a window of opportunity for early identification of diabetes and prediabetes, as women with history of GDM are at increased risk of future glucose intolerance. © Academy of Family Physicians of Malaysia.Background The endocrine disruptor Bisphenol-A (BPA), has been involved in dysregulating adipose tissue development and increasing the risk of obesity. The objective of this experiment was to investigate whether treatment of human mesenchymal stem cells with BPA could modulate adipogenesis and adipocyte differentiation. Methods In this experimental study, the human adipose-derived mesenchymal stem cells (hASCs) were cultured for 2 weeks with continuous exposure to 10- 10 M or 10- 8 M concentrations of BPA. The extent of triglyceride accumulation was visualized by Oil Red O staining. To evaluate BPA effect on the expression levels of key adipogenic trascripotion factors and proteins, we used Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and ELISA. Results The results presented a dose-dependent triglyceride accumulation in treated cells with BPA. Additionally, we observed that BPA induced transcription of the Peroxisome proliferator-activated receptor-gamma (PPARγ), CCAAT-enhancer-binding protein-alpha (C/EBPα), CCAAT-enhancer-binding protein-beta (C/EBPβ), sterol regulatory element-binding protein-1c (SREBP1c), Fatty acid synthase (FASN), and lipoprotein lipase (LPL); BPA suppressed the expression of Fatty acid binding protein-4 (FABP4) and Estrogen receptor-beta (ERβ). Conclusions Our findings supported the hypothesis that BPA enhances adipogenic differentiation thereby may play a role in development of obesity and dysregulation of metabolic homoeostasis. © The Author(s) 2020.Introduction Colibactin is a small genotoxic molecule produced by enteric bacteria, including certain Escherichia coli (E. coli) strains harbored in the human large intestine. This polyketide-peptide genotoxin is considered to contribute to the development of colorectal cancer. The colibactin-producing (clb +) microorganisms possess a 54-kilobase genomic island (clb gene cluster). In the present study, to assess the distribution of the clb gene cluster, genotyping analysis was carried out among E. coli strains randomly chosen from the Japan Collection of Microorganisms, RIKEN BRC, Japan. Findings The analysis revealed that two of six strains possessed a clb gene cluster. These clb + strains JCM5263 and JCM5491 induced genotoxicity in in vitro micronucleus (MN) tests using rodent CHO AA8 cells. Since the induction level of MN by JCM5263 was high, a bacterial umu test was carried out with a cell extract of the strain, revealing that the extract had SOS-inducing potency in the umu tester bacterium. Conclusion These results support the observations that the clb gene cluster is widely distributed in nature and clb + E. coli having genotoxic potencies is not rare among microorganisms. © The Author(s) 2020.Background Tuberculosis (TB) is a major public health concern in the developing world. World Health Organization's (WHO's) list of 30 high TB burden countries accounted for 87% of the world's cases. The annual infection rate in developing countries reached 2% or more; where as in developed countries this figure is 0.5%. Objective The objective of this study is to assess treatment outcomes of tuberculosis retreatment case and its determinants at Nekemte Referral Hospital (NRH), West Ethiopia. Methods A retrospective cross-sectional study was conducted. All registered adult TB patients under retreatment regimen who were treated at NRH TB clinics from January 2014 to December 2017 were included in this study. A multiple logistic regression was used to assess the significance and strength of association. A P-value less then 0.05 was used as statistically significant. Results The prevalence of retreatment case was 12.12%. Of 219 study participants 159(72.6%) were patients with relapse, 43(19.6%) were with retreatment after failure and 17(7.8%) were patients who return after loss to follow-up. On multivariable logistic analysis poor treatment outcome was more likely to occur among patients with positive Acid Fast Bacilli (AFB) result at 5th month (Adjusted odds ratio (AOR =4.3, 95%, (1.8-10.0) p=0.001) and patients taking category 1 (2ERHZ/4RH) drugs (AOR=2.1, 95% CI= (1.1-4.5) p=0.048). Conclusion This study showed that treatment outcomes of TB retreatment case were below standard set by the WHO. Factors that were significantly associated with poor treatment outcome were positive AFB resulting at 5th month and patients on category 1(2ERHZ/4RH). © 2019 Bentham Science Publishers.Introduction Proapoptotic peptide, (KLAKLAK)2, exhibits strong anti-tumor effect with the help of cell-penetrating peptides such as Pep2, targeting TLR2 with high expression in acute myeloid leukemia (AML). However, the applications are limited due to the peptide's instability and high cost of synthesis. Recombinant PP7 bacteriophage-like particles (VLPs) can protect the peptides from degradation by proteases, based on their ability to display foreign peptides. Methods Here, we evaluated the feasibility of PP7 VLPs carrying Pep2 and (KLAKLAK)2 (2PP7-Pep2-KLAK VLPs) expressed in E. coli. We further investigated the characteristics including size, toxicity, thermal stability, penetrating ability, anti-tumor activity, and potential anti-tumor mechanism of 2PP7-Pep2-KLAK VLPs. Results 2PP7-Pep2-KLAK VLPs was expressed in E. coli BL21(DE3) successfully with high yield and thermal stability. They penetrated the AML cells THP-1 rapidly after 30 min of incubation. Moreover, 2PP7-Pep2-KLAK VLPs were non-replicative, non-infectious, and non-toxic against normal cells, but inhibited the proliferation of THP-1 cells by inducing cell apoptosis after 24 h of exposure. This effect extends through 120 h of exposure, indicating their anti-proliferation effect was superior to that of synthetic peptides. In addition to the mitochondrial apoptotic pathway, the anti-tumor activity of 2PP7-Pep2-KLAK VLPs was also correlated with down-regulation of expression of enhancer of zeste homolog 2 (EZH2) and trimethylation of histone H3K27. Conclusions We identified the feasibility to prepare the stable, active Pep2-KLAK peptide by using PP7 bacteriophage as the vehicle. We revealed this peptide was an inhibitor of EZH2. 2PP7-Pep2-KLAK VLPs may have significant clinical implications in the treatment of MLL-AF9 AML as an epigenetic modulator. © Biomedical Engineering Society 2019.Background Diabetes mellitus is characterized by hyperglycemia which displays insufficiency or resistance to insulin. One of the complications of diabetes is the increased risk of fracture and the impairment of bone repair and regulation. Zoligratinib molecular weight There have been evidences from previous studies that mesenchymal stem cells (MSCs) from bone marrow promote cartilage and callous formation. In addition, IL-10, an anti-inflammatory cytokine, has been observed to relieve inflammation-related complications in diabetes. Methods In this study, the role of IL-10-overexpressing bone marrow-derived MSCs (BM-MSCs) was examined in the diabetic mice model with femur fracture. MSCs were isolated from the BALB/c mice and IL-10 over expression was conducted with lentivirus transduction. The streptozotocin (STZ)-induced diabetes model with femoral fracture was established. BM-MSCs with IL-10 over expression were transplanted into the fracture area. The expressions of inflammatory factors IL-6, TNF-α and INF-γ were examined by qPCR and immunoblot; the biomechanical strength of the fracture site of the mice was examined and evaluated. Results Data showed that IL-10 overexpressed BM-MSCs transplantation decreased inflammatory response, promoted bone formation, and increased the strength of the fracture site in STZ-induced diabetic mice with femoral fracture. Conclusion IL-10 overexpressed BM-MSCs transplantation accelerated fracture repair in STZ-induced diabetic mice, which in turn provides potential clinical application prospects. © Biomedical Engineering Society 2019.Introduction The adhesion of tumor cells to vessel wall is a critical stage in cancer metastasis. Firm adhesion of cancer cells is usually followed by their extravasation through the endothelium. Despite previous studies identifying the influential parameters in the adhesive behavior of the cancer cell to a planer substrate, less is known about the interactions between the cancer cell and microvasculature wall and whether these interactions exhibit organ specificity. The objective of our study is to characterize sizes of microvasculature where a deformable circulating cell (DCC) would firmly adhere or roll over the wall, as well as to identify parameters that facilitate such firm adherence and underlying mechanisms driving adhesive interactions. Methods A three-dimensional model of DCCs is applied to simulate the fluid-structure interaction between the DCC and surrounding fluid. A dynamic adhesion model, where an adhesion molecule is modeled as a spring, is employed to represent the stochastic receptor-ligand interactions using kinetic rate expressions. Results Our results reveal that both the cell deformability and low shear rate of flow promote the firm adhesion of DCC in small vessels ( less then 10 μ m ). Our findings suggest that ligand-receptor bonds of PSGL-1-P-selectin may lead to firm adherence of DCC in smaller vessels and rolling-adhesion of DCC in larger ones where cell velocity drops to facilitate the activation of integrin-ICAM-1 bonds. Conclusions Our study provides a framework to predict accurately where different DCC-types are likely to adhere firmly in microvasculature and to establish the criteria predisposing cancer cells to such firm adhesion. © Biomedical Engineering Society 2020.Introduction The pathophysiological increase in microvascular permeability plays a well-known role in the onset and progression of diseases like sepsis and atherosclerosis. However, how interactions between neutrophils and the endothelium alter vessel permeability is often debated. Methods In this study, we introduce a microfluidic, silicon-membrane enabled vascular mimetic (μSiM-MVM) for investigating the role of neutrophils in inflammation-associated microvascular permeability. In utilizing optically transparent silicon nanomembrane technology, we build on previous microvascular models by enabling in situ observations of neutrophil-endothelium interactions. To evaluate the effects of neutrophil transmigration on microvascular model permeability, we established and validated electrical (transendothelial electrical resistance and impedance) and small molecule permeability assays that allow for the in situ quantification of temporal changes in endothelium junctional integrity. Results Analysis of neutrophil-expressed β1 integrins revealed a prominent role of neutrophil transmigration and basement membrane interactions in increased microvascular permeability.