Effect of human immunodeficiency virus on the brain: a review

CITATION: Cilliers, K. & Muller, C. J. F. 2021. Effect of human immunodeficiency virus on the brain: A review. The Anatomical Record, 304:1389– 1399. doi:10.1002/ar.24573The original publication is available at https://anatomypubs.onlinelibrary.wiley.com/journal/19328494Thirty million people are infected with human immunodeficiency virus (HIV) worldwide, and HIV-associated neurocognitive disorder (HAND) is one of the most common comorbidities of HIV. However, the effect of HIV on the brain has not been fully investigated. This article aimed to review the changes to the brain due to HIV in terms of atrophy, diffusion changes, and hyperintensities. Studies have observed significant atrophy in subcortical gray matter, as well as in cortical white and gray matter. Moreover, the ventricles enlarge, and the sulci widen. Although HIV causes changes to the white and gray matter of the brain, few diffusion tensor imaging studies have investigated the changes to gray matter integrity. White and gray matter hyperintensities have frequently been observed in HIV-positive individuals, with the subcortical gray matter (caudate nucleus and putamen) and periventricular white matter frequently affected. In conclusion, subcortical gray matter is the first brain region to be affected and is affected most severely. Additionally, this review highlights the gaps in the literature, since the effect of HIV on the brain is not fully known. Future studies should continue to investigate the effect of HIV on the brain in different stages of the disease, and alternate therapies should be developed since highly active antiretroviral therapy is currently ineffective at treating HAND.https://anatomypubs.onlinelibrary.wiley.com/doi/10.1002/ar.24573Publisher’s versio

Trace element concentration changes in brain tumors : a review

CITATION: Cilliers, K. et al. 2020. Trace element concentration changes in brain tumors: a review. The Anatomical Record, 303:1293-1299. doi:10.1002/ar.24254The original publication is available at https://anatomypubs.onlinelibrary.wiley.com/journal/19328494Trace elements have been implicated in cancer, since the levels differ between cancerous and noncancerous tissue, different cancer types, and different malignancy grades. However, few studies have been conducted on trace element concentrations in brain tumors. Thus, this study aims to review the available literature on trace element changes related to brain tumors, and to identify gaps in the literature. A literature search was done on Google Scholar and PubMed from their start date to January 2018, using terms related to trace element concentration and brain tumors. All brain tumor types were included, and articles could be published in any year. From this search, only 11 articles on this topic could be found. Tumors had significantly higher concentrations of arsenic, thorium, lanthanum, lutetium, cerium, and gadolinium compared to control brain samples. Compared to adjacent tissue, tumor tissue indicated increased magnesium, decreased copper, and contradicting results for zinc. Furthermore, the higher the malignancy grade, the lower the calcium, cadmium, iron, phosphorus and sulfur concentration, and the higher the mercury, manganese, lead, and zinc concentrations. In conclusion, altered trace element levels differ amongst different tumor types, as well as malignancy grades. Consequently, it is impossible to compare data from these studies, and available data are still considerably inconclusive. Ideally, future studies should have a sufficient samples size, compare different tumor types, and compare tumors with adjacent healthy tissue as well as with samples from unaffected matched brains. Anat Rec, 303:1293-1299, 2020. © 2019 American Association for Anatomy.https://anatomypubs.onlinelibrary.wiley.com/doi/full/10.1002/ar.24254Publisher’s versio

Identification of antidiabetic compounds from the aqueous extract of Sclerocarya birrea leaves

SUPPLEMENTARY MATERIALS : TABLE S1: 1H NMR and 13C NMR data of Myricetin (1) in methanol-d4 compared to those reported [35] in DMSO-d6; TABLE S2: 1H NMR and 13C NMR data of Myricetin-3-O-β-D-glucuronide (2) in methanol-d4 compared to those reported [36] in methanol-d4; TABLE S3: 1H NMR and 13C NMR data of Quercetin-3-O-β-D-glucuronide (3) in methanol-d4 compared to those reported by [37] in methanol-d4; FIGURE S4: Relative Glucose uptake activity of Marula fractions in C2C12 myocytes over a range of 0.01-100µg/ml. Activity is expressed relative % to the baseline glucose uptake (control) set at 0% and the positive control insulin (Ins) set at 100%. Active fraction (fraction 3) exhibited comparable potency to Insulin. p value < * p < 0.05, ** p < 0.01. *** p < 0.001; FIGURE S5: ESI negative-mode BPI chromatogram of compound 1 (Myricetin) isolated from Fraction 4; FIGURE S6: ESI negative-mode BPI chromatogram of compound 2 (Myricetin3-O-β-D-glucuronide) isolated from Fraction 3; FIGURE S7: ESI negative-mode BPI chromatogram of compound 3 (Quercetin-3-O-β-D-glucuronide) isolated from Fraction 3; FIGURE S8: MS fragmentation pattern of peak 1 overlaid with MSMS fragmentation pattern of peak 1; FIGURE S9: MS fragmentation pattern of peak 2 overlaid with MSMS fragmentation pattern of peak 2; FIGURE S10: MS fragmentation pattern of peak 3 overlaid with MSMS fragmentation pattern of peak 3; FIGURE S11: MS fragmentation pattern of peak 4 overlaid with MSMS fragmentation pattern of peak 4; FIGURE S12: MS fragmentation pattern of peak 5 overlaid with MSMS fragmentation pattern of peak 5; FIGURE S13: MS fragmentation pattern of peak 6 overlaid with MSMS fragmentation pattern of peak 6.DATA AVAILABILITY STATEMENT : All the data supporting the findings of this study are available within the article and/or its Supplementary Materials.Diabetes, a prevalent metabolic condition with a wide range of complications, is fast becoming a global health crisis. Herbal medicine and enhanced extracts are some of the therapeutic options used in the management of diabetes mellitus. The plant-derived molecules and their suitable structure modification have given many leads or drugs to the world such as metformin used as an antidiabetic drug. The stem extract of Sclerocarya birrea has been reported as a potent antidiabetic (glucose uptake) agent. However, the bioactive compounds have not been reported from S. birrea for treatment of diabetes. In this study, the spray-dried aqueous leaf extracts of S. birrea were investigated as an antidiabetic agent using a 2-deoxy-glucose (2DG) technique showing good stimulatory effect on glucose uptake in differentiated C2C12 myocytes with % 2DG uptake ranging from 110–180% that was comparable to the positive control insulin. Three compounds were isolated and identified using bioassay-guided fractionation of the spray-dried aqueous extract of S. birrea leaves: myricetin (1), myricetin-3-O- -D-glucuronide (2) and quercetin-3-O- -D-glucuronide (3). Their chemical structures were determined using NMR and mass spectrometric analyses, as well as a comparison of experimentally obtained data to those reported in the literature. The isolated compounds (1–3) were studied for their stimulatory actions on glucose uptake in differentiated C2C12 myocytes. The three compounds (1, 2 and 3) showed stimulatory effects on the uptake of 2DG in C2C12 myocytes with % 2DG uptake ranging from 43.9–109.1% that was better compared to the positive control insulin. Additionally, this is the first report of the flavonoid glycosides (myricetin-3-O- -D-glucuronide) for antidiabetic activity and they are the main bioactive compound in the extract responsible for the antidiabetic activity. This result suggests that the S. birrea leaves have the potential to be developed for treatment of diabetes.The Department of Science and Innovation, South Africa, University of KwaZulu-Natal, South Africa and Biomedical Research and Innovation Platform, South African Medical Research Council.https://www.mdpi.com/journal/moleculesam2023Chemistr

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

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

Coenzyme Q10 supplementation improves adipokine levels and alleviates inflammation and lipid peroxidation in conditions of metabolic syndrome : a meta-analysis of randomized controlled trials

CITATION: Dludla, P. V., et al. 2020. Q10 Supplementation Improves Adipokine Levels and Alleviates Inflammation and Lipid Peroxidation in Conditions of Metabolic Syndrome: A Meta-Analysis of Randomized Controlled Trials. International Journal of Molecular Sciences. 2020; 21(9). doi:10.3390/ijms21093247The original publication is available at https://www.mdpi.com/journal/ijmsEvidence from randomized controlled trials (RCTs) suggests that coenzyme Q10 (CoQ10) can regulate adipokine levels to impact inflammation and oxidative stress in conditions of metabolic syndrome. Here, prominent electronic databases such as MEDLINE, Cochrane Library, and EMBASE were searched for eligible RCTs reporting on any correlation between adipokine levels and modulation of inflammation and oxidative stress in individuals with metabolic syndrome taking CoQ10. The risk of bias was assessed using the modified Black and Downs checklist, while the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool was used to evaluate the quality of evidence. Results from the current meta-analysis, involving 318 participants, showed that CoQ10 supplementation in individuals with metabolic syndrome increased adiponectin levels when compared to those on placebo (SMD: 1.44 [95% CI: −0.13, 3.00]; I2 = 96%, p < 0.00001). Moreover, CoQ10 supplementation significantly lowered inflammation markers in individuals with metabolic syndrome in comparison to those on placebo (SMD: −0.31 [95% CI: −0.54, −0.08]; I2 = 51%, p = 0.07). Such benefits with CoQ10 supplementation were related to its ameliorative effects on lipid peroxidation by reducing malondialdehyde levels, concomitant to improving glucose control and liver function. The overall findings suggest that optimal regulation of adipokine function is crucial for the beneficial effects of CoQ10 in improving metabolic health.https://www.mdpi.com/1422-0067/21/9/3247/htmPublishers versio

The Effect of Phytochemicals and Food Bioactive Compounds on Diabetes

There are three main types of diabetes, namely, type 1 diabetes, type 2 diabetes (T2D), and diabetes in pregnancy (gestational diabetes) [...

In vitro comparison of various antioxidants and flavonoids from Rooibos as beta cell protectants against lipotoxicity and oxidative stress-induced cell death.

Oxidative stress and lipotoxicity effects on pancreatic β cells play a major role in the pathogenesis of type 2 diabetes (T2D). Flavonoids and antioxidants are under study for their cytoprotective effects and antidiabetic potential. In this study, we aimed to compare the protective effect of the Rooibos components aspalathin, isoorientin, 3-hydroxyphloretin (3-OH) and green Rooibos extract (GRT) itself, and exendin-4 and N-acetylcysteine (NAC) as reference molecules, against lipotoxicity and oxidative stress. The insulin-producing β cell line INS1E was exposed to hydrogen peroxide or streptozotocin (STZ) to induce oxidative stress, and palmitate to induce lipotoxicity. Cell viability was assessed by a MTS cell viability assay. Antioxidant response and antiapoptotic gene expression was performed by qRT-PCR. Glucose transporter 2 (GLUT 2) transporter inhibition was assessed through 2-NBDG uptake. GRT and the flavonoids aspalathin and 3-hydroxyphloretin offered significant protection against oxidative stress and lipotoxicity. GRT downregulated expression of pro-apoptotic genes Txnip and Ddit3. The flavonoids aspalathin and 3-hydroxyphloretin also downregulated these genes and in addition upregulated expression of antioxidant response genes Hmox1, Nqo1 and Sod1. Isoorientin gave no cytoprotection. Cytoprotection by Rooibos components was significantly higher than by NAC or exendin-4. Rooibos components strongly protect INS1E β cells against diabetogenic stress. Cytoprotection was associated with the upregulation of antioxidant response genes of the NRF2/KEAP1 pathway or suppression of the TXN system. The Rooibos molecules offered better protection against these insults than exendin-4 and NAC, making them interesting candidates as β cell cytoprotectants for therapeutic or nutraceutical applications

New Insights into the Efficacy of Aspalathin and Other Related Phytochemicals in Type 2 Diabetes&mdash;A Review

In the pursuit of bioactive phytochemicals as a therapeutic strategy to manage metabolic risk factors for type 2 diabetes (T2D), aspalathin, C-glucosyl dihydrochalcone from rooibos (Aspalathus linearis), has received much attention, along with its C-glucosyl flavone derivatives and phlorizin, the apple O-glucosyl dihydrochalcone well-known for its antidiabetic properties. We provided context for dietary exposure by highlighting dietary sources, compound stability during processing, bioavailability and microbial biotransformation. The review covered the role of these compounds in attenuating insulin resistance and enhancing glucose metabolism, alleviating gut dysbiosis and associated oxidative stress and inflammation, and hyperuricemia associated with T2D, focusing largely on the literature of the past 5 years. A key focus of this review was on emerging targets in the management of T2D, as highlighted in the recent literature, including enhancing of the insulin receptor and insulin receptor substrate 1 signaling via protein tyrosine phosphatase inhibition, increasing glycolysis with suppression of gluconeogenesis by sirtuin modulation, and reducing renal glucose reabsorption via sodium-glucose co-transporter 2. We conclude that biotransformation in the gut is most likely responsible for enhancing therapeutic effects observed for the C-glycosyl parent compounds, including aspalathin, and that these compounds and their derivatives have the potential to regulate multiple factors associated with the development and progression of T2D