Cultivating Capital for High School Newcomers: A Case Study of an Urban Newcomer Classroom

This qualitative case study examines how students in a high school newcomer program experience the development of social and cultural capital. Newcomer programs are created by K-12 schools with large influxes of refugees and immigrants. This case study data stems from a larger ethnographic study of a newcomer program at Georgetown High, an urban secondary school in the Northeast region of the United States. Using Bourdieu’s (1986) social and cultural capital theory as a framework for the study we provide an overview of the literature on the importance of helping newcomers build social and cultural capital. Themes arising from the data as representations of the experiences of newcomers building capital and the role of the teacher in that development is explored further. The paper concludes with a discussion of implications of the case for research, policy, and practice

Blood-Based DNA Methylation Biomarkers for Type 2 Diabetes: Potential for Clinical Applications

Type 2 diabetes (T2D) is a leading cause of death and disability worldwide. It is a chronic metabolic disorder that develops due to an interplay of genetic, lifestyle, and environmental factors. The biological onset of the disease occurs long before clinical symptoms develop, thus the search for early diagnostic and prognostic biomarkers, which could facilitate intervention strategies to prevent or delay disease progression, has increased considerably in recent years. Epigenetic modifications represent important links between genetic, environmental and lifestyle cues and increasing evidence implicate altered epigenetic marks such as DNA methylation, the most characterized and widely studied epigenetic mechanism, in the pathogenesis of T2D. This review provides an update of the current status of DNA methylation as a biomarker for T2D. Four databases, Scopus, Pubmed, Cochrane Central, and Google Scholar were searched for studies investigating DNA methylation in blood. Thirty-seven studies were identified, and are summarized with respect to population characteristics, biological source, and method of DNA methylation quantification (global, candidate gene or genome-wide). We highlight that differential methylation of the TCF7L2, KCNQ1, ABCG1, TXNIP, PHOSPHO1, SREBF1, SLC30A8, and FTO genes in blood are reproducibly associated with T2D in different population groups. These genes should be prioritized and replicated in longitudinal studies across more populations in future studies. Finally, we discuss the limitations faced by DNA methylation studies, which include including interpatient variability, cellular heterogeneity, and lack of accounting for study confounders. These limitations and challenges must be overcome before the implementation of blood-based DNA methylation biomarkers into a clinical setting. We emphasize the need for longitudinal prospective studies to support the robustness of the current findings of this review

The determination of the effect(s) of solute carrier family 22‑member 2 (SLC22A2) haplotype variants on drug binding via molecular dynamic simulation systems

Single nucleotide polymorphisms detected in the solute carrier member family-22 has been shown to result in a variable response in the treatment of type 2 diabetes mellitus with Metformin. This study predicted a three-dimensional protein structure for the SLC22A2 protein sequence using AlphaFold 2 and modelled five haplotypes within SLC22A2 protein structure observed in the Xhosa population of South Africa. The protein models were used to determine the effect(s) of haplotype variations on the transport function of Metformin and 10 other drugs by the SLC22A2 protein. Molecular dynamic simulation studies, molecular docking and interaction analysis of the five SLC22A2 haplotypes were performed in complex with the ligand 5RE in a POPC lipid bilayer to understand the mechanism of drug binding

An in vitro study on the combination effect of metformin and N-Acetyl cysteine against hyperglycaemia-Induced cardiac damage

Chronic hyperglycaemia is a major risk factor for diabetes-induced cardiovascular dysfunction. In a hyperglycaemic state, excess production of reactive oxygen species (ROS), coupled with decreased levels of glutathione, contribute to increased lipid peroxidation and subsequent myocardial apoptosis. N-acetylcysteine (NAC) is a thiol-containing antioxidant known to protect against hyperglycaemic-induced oxidative stress by promoting the production of glutathione. While the role of NAC against oxidative stress-related cardiac dysfunction has been documented, to date data is lacking on its beneficial effect when used with glucose lowering therapies, such as metformin (MET). Thus, the aim of the study was to better understand the cardioprotective effect of NAC plus MET against hyperglycaemia-induced cardiac damage in an H9c2 cardiomyoblast model. H9c2 cardiomyoblasts were exposed to chronic high glucose concentrations for 24 h. Thereafter, cells were treated with MET, NAC or a combination of MET and NAC for an additional 24 h. The combination treatment mitigated high glucose-induced oxidative stress by improving metabolic activity i.e. ATP activity, glucose uptake (GU) and reducing lipid accumulation. The combination treatment was as effective as MET in diminishing oxidative stress, lipid peroxidation and apoptosis. We observed that the combination treatment prevented hyperglycaemic-induced cardiac damage by increasing GLUT4 expression and mitigating lipid accumulation via phosphorylation of both AMPK and AKT, while decreasing nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), as well as protein kinase C (PKC), a known activator of insulin receptor substrate-1 (IRS-1), via phosphorylation at Ser307. On this basis, the current results support the notion that the combination of NAC and MET can shield the diabetic heart against impaired glucose utilization and therefore its long-term protective effect warrants further investigation

Cross-sectional study of the association of 5 single nucleotide polymorphisms with enalapril treatment response among South African adults with hypertension

This study investigates the association of 5 single nucleotide polymorphisms (SNPs) in selected genes (ABO, VEGFA, BDKRB2, NOS3, and ADRB2) with blood pressure (BP) response to enalapril. The study further assessed genetic interactions that exist within these genes and their implications in enalapril treatment response among South African adults with hypertension.A total of 284 participants belonging to the Nguni tribe of South Africa on continuous treatment for hypertension were recruited. Five SNPs in enalapril pharmacogenes were selected and genotyped using MassArray. Uncontrolled hypertension was defined as BP ≥140/90 mm Hg. The association between genotypes, alleles, and BP response to treatment was determined by fitting multivariate logistic regression model analysis, and genetic interactions between SNPs were assessed by multifactor dimensionality reduction.Majority of the study participants were female (75.00%), Xhosa (78.87%), and had uncontrolled hypertension (69.37%). All 5 SNPs were exclusively detected among Swati and Zulu participants. In the multivariate (adjusted) logistic model analysis, ADRB2 rs1042714 GC (adjusted odds ratio [AOR] = 2.31; 95% confidence interval [CI] 1.02-5.23; P = .044) and BDKRB2 rs1799722 CT (AOR = 2.74; 95% CI 1.19-6.28; P = .017) were independently associated with controlled hypertension in response to enalapril. While the C allele of VEGFA rs699947 (AOR = 0.37; 95% CI 0.15-0.94; P = .037) was significantly associated with uncontrolled hypertension. A significant interaction between rs699947, rs495828, and rs2070744 (cross-validation consistency = 10/10; P = .0005) in response to enalapril was observed.We confirmed the association of rs1042714 (ADRB2) and rs1799722 (BDKRB2) with controlled hypertension and established an interaction between rs699947 (VEGFA), rs495828 (ABO), and rs2070744 (NOS3) with BP response to enalapril. Our findings have provided substantial evidence for the use of SNPs as predictors for enalapril response among South Africans adults with hypertension. Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc

The effect of adiponectin in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and the potential role of polyphenols in the modulation of adiponectin signaling

CITATION: Shabalala, Samukelisiwe C. et al. 2020. The effect of adiponectin in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and the potential role of polyphenols in the modulation of adiponectin signaling. Biomed Pharmacotherapy, 131:110785, doi:10.1016/j.biopha.2020.110785.The original publication is available at: https://www.sciencedirect.comNon-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, as it affects up to 30 % of adults in Western countries. Moreover, NAFLD is also considered an independent risk factor for cardiovascular diseases. Insulin resistance and inflammation have been identified as key factors in the pathophysiology of NAFLD. Although the mechanisms associated with the development of NAFLD remain to be fully elucidated, a complex interaction between adipokines and cytokines appear to play a crucial role in the development of this condition. Adiponectin is the most common adipokine known to be inversely linked with insulin resistance, lipid accumulation, inflammation and NAFLD. Consequently, the focus has been on the use of new therapies that may enhance hepatic expression of adiponectin downstream targets or increase the serum levels of adiponectin in the treatment NAFLD. While currently used therapies show limited efficacy in this aspect, accumulating evidence suggest that various dietary polyphenols may stimulate adiponectin levels, offering potential protection against the development of insulin resistance, inflammation and NAFLD as well as associated conditions of metabolic syndrome. As such, this review provides a better understanding of the role polyphenols play in modulating adiponectin signaling to protect against NAFLD. A brief discussion on the regulation of adiponectin during disease pathophysiology is also covered to underscore the potential protective effects of polyphenols against NAFLD. Some of the prominent polyphenols described in the manuscript include aspalathin, berberine, catechins, chlorogenic acid, curcumin, genistein, piperine, quercetin, and resveratrol.Publisher's versio

The triterpene, methyl-3β-hydroxylanosta-9,24-dien-21-oate (RA3), attenuates high glucose-induced oxidative damage and apoptosis by improving energy metabolism

BACKGROUND: Hyperglycemia-induced cardiovascular dysfunction has been linked to oxidative stress and accelerated apoptosis in the diabetic myocardium. While there is currently no treatment for diabetic cardiomyopathy (DCM), studies suggest that the combinational use of anti-hyperglycemic agents and triterpenes could be effective in alleviating DCM. HYPOTHESIS: To investigate the therapeutic effect of methyl-3β-hydroxylanosta-9,24-dien-21-oate (RA3), in the absence or presence of the anti-diabetic drug, metformin (MET), against hyperglycemia-induced cardiac injury using an in vitro H9c2 cell model. METHODS: To mimic a hyperglycemic state, H9c2 cells were exposed to high glucose (HG, 33 mM) for 24 h. Thereafter, the cells were treated with RA3 (1 μM), MET (1 μM) and the combination of MET (1 μM) plus RA3 (1 μM) for 24 h, to assess the treatments therapeutic effect. RESULTS: Biochemical analysis revealed that RA3, with or without MET, improves glucose uptake via insulindependent (IRS-1/PI3K/Akt signaling) and independent (AMPK) pathways whilst ameliorating the activity of antioxidant enzymes in the H9c2 cells. Mechanistically, RA3 was able to alleviate HG-stimulated oxidative stress through the inhibition of reactive oxygen species (ROS) and lipid peroxidation as well as the reduced expression of the PKC/NF-кB cascade through decreased intracellular lipid content. Subsequently, RA3 was able to mitigate HG-induced apoptosis by decreasing the activity of caspase 3/7 and DNA fragmentation in the cardiomyoblasts. CONCLUSION: RA3, in the absence or presence of MET, demonstrated potent therapeutic properties against hyperglycemia-mediated cardiac damage and could be a suitable candidate in the prevention of DCM.South African National Treasury and National Research Foundation.https://www.elsevier.com/locate/phymedpm2022BiochemistryGeneticsMicrobiology and Plant Patholog

Sclerocarya birrea (marula) extract inhibits hepatic steatosis in db/db mice

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of hepatic metabolic perturbations ranging from simple steatosis to steatohepatitis, cirrhosis and hepatocellular carcinoma. Currently, lifestyle modifications to reduce weight gain are considered the most effective means of preventing and treating the disease. The aim of the present study was to determine the therapeutic benefit of Sclerocarya birrea (Marula leaf extract, MLE) on hepatic steatosis. Obese db/db mice were randomly stratified into the obese control, metformin (MET) or MLE-treated groups. Mice were treated daily for 29 days, at which point all mice were euthanized and liver samples were collected. Hematoxylin and eosin staining was used for histological assessment of the liver sections, while qRT-PCR and Western blot were used to determine hepatic mRNA and protein expression, respectively. Thereafter, the association between methylenetetrahydrofolate reductase (Mthfr a key enzyme in one-carbon metabolism and DNA-methylation-induced regulation of gene transcription) and lipogenic genes was evaluated using Pearson’s correlation coefficient. Mice treated with MLE presented with significantly lower body and liver weights as compared with the obese control and MET-treated mice (p ≤ 0.05). Further, MLE treatment significantly inhibited hepatic steatosis as compared with the obese control and MET-treated mice (p ≤ 0.05). The reduced lipid accumulation was associated with low expression of fatty acid synthase (Cpt1; p ≤ 0.05) and an upregulation of the fatty acid oxidation gene, carnitine palmitoyltransferase (Cpt1; p ≤ 0.01), as compared with the obese control mice. Interestingly, MLE treatment improved the correlation between Mthfr and Cpt1 mRNA expression (r = 0.72, p ≤ 0.01). Taken together, the results suggest that Marula leaf extracts may inhibit hepatic steatosis by influencing the association between Mthfr and genes involved in hepatic lipid metabolism. Further studies are warranted to assess DNA methylation changes in lipid metabolism genes.The National Research Foundation and by baseline funding of the South African Medical Research Council’s Division of Biomedical Research and Innovation Platform.https://www.mdpi.com/journal/ijerphChemistr