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

An Immunocytochemical Profile of the Endocrine Pancreas Using an Occlusive Duct Ligation Model

Context Ligation of the pancreatic duct, distally to its confluence into the bile duct has been shown to induce endocrine tissue regeneration. The surplus endocrine tissue formed is presumed to be able to replace pathologically and/or experimentally compromised tissue. Objective This is a quantitative study on the histology of duct ligated pancreas employing immunocytochemistry and computerised morphometry. Interventions Pancreatic duct ligation was performed on 25 groups of six normal Sprague-Dawley rats. Experimental animals were sacrificed at 12-hour intervals from day one to ten post-duct ligation and every 24 hours thereafter to day 14, the pancreas removed, fixed and processed. Six consecutive 3-6 micron serial sections were cut on a rotary hand microtome, floated onto 3-aminopropyl-trimethoxysilan coated slides and alternatively immunocytochemically stained for insulin, glucagon, pancreatic polypeptide and somatostatin. Results Pancreas transformation between days ½ and 3½ was characterised by acinar deletion and the appearance of immunoreactive cells for the primary endocrine hormones. Transdifferentiation of existing endocrine tissue saw islet insulin core cells replaced by pancreatic polypeptide- and somatostatin positive cells, glucagon deletion and random appearance of all endocrine cell types within the inter-islet interstitium by day 3½. Days 4 to 14 were characterised by cellular migration and islet reconstruction. Conclusions To date our laboratory has investigated transplantation of foetal tissue beneath the renal capsule in syngeneic, isogeneic and allogeneic normal and diabetic rats. As pancreatic duct ligation induces the development of surplus endocrine tissue our next step would be to investigate the use of ligated pancreas as a replacement for foetal tissue.Image: Arrangement of bile and pancreatic ducts in the laboratory rat

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

A high fat, high sugar diet induces hepatic peroxisome proliferator-activated receptor gamma coactivator 1-alpha promoter hypermethylation in male Wistar rats

DATA AVAILABILITY STATEMENT : The datasets generated for this study are available from www.kaggle.com/dataset/e76461efceddbae54b4f6b5b32441cd5eecd212558a3d169485fe2798a6d26a8.Previously we reported that a high fat, high sugar (HFHS) diet induced adiposity, hyperinsulinaemia, hyperleptinaemia, hypertriglyceridaemia and increased liver mass in male Wistar rats. In the present study, the mechanisms underlying the increased liver mass were further elucidated by assessing hepatic lipid accumulation and the expression and methylation status of key metabolic genes using histology, quantitative real-time PCR and pyrosequencing, respectively. The HFHS diet induced hepatic steatosis, increased hepatic triglycerides (1.8-fold, p < 0.001), and increased the expression of sterol regulatory element-binding transcription factor 1 (Srebf1) (2.0- fold, p < 0.001) and peroxisome proliferator-activated receptor gamma (Pparg) (1.7-fold, p = 0.017) in the liver. The expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (Pgc1a) was decreased (2.6-fold, p < 0.010), which was accompanied by hypermethylation (p = 0.018) of a conserved CpG site in the promoter of Pgc1a in HFHS fed rats compared to controls. In silico analysis identified putative binding sites for CCAAT/enhancer-binding protein beta (C/EBPß) and hepatocyte nuclear factor 1 (HNF1) within proximity to the hypermethylated CpG. As Pgc1a is a co-activator of several transcription factors regulating multiple metabolic pathways, hypermethylation of this conserved CpG site in the promoter of Pgc1a may be one possible mechanism contributing to the development of hepatic steatosis in response to a HFHS diet. However, further work is required to confirm the role of Pgc1a in steatosis.The Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC) and the National Research Foundation (NRF) professional development programme (PDP).http://www.elsevier.com/locate/ybbrcam2024Obstetrics and GynaecologySDG-03:Good heatlh and well-bein

In vitro and in vivo hepatotoxicity study of Afriplex™ GRT through an inflammatory response

BACKGROUND : The focus on traditional and complementary medicine for supplementation and treatment of diseases is high. Aspalathus linearis commonly known as Rooibos showed several beneficial effects, this led to the standardized production of a pharmaceutical grade green rooibos extract (Afriplex TM GRT) with enhanced polyphenolic content. The aim of this study was to assess toxicity of Afriplex TM GRT in HepG2/C3A cells and Sprague Dawley rats. METHODS : Afriplex GRT TM (0.1, 1, 10, 100, or 1000 μg/mL) in DMSO was added to the media to the final 0.01% DMSO for treatment of HepG2/C3A for 1, 24 and 48 hrs followed by MTT and ATP assays. Sprague Dawley rats were grouped to Control, Afriplex TM GRT treated (10, 100 and 300 mg/kg); and acute (24hrs tetrachloromethane (CCl 4) injected hepatotoxicity control). Serum biochemistry, histology and Western blot analysis on liver were performed. RESULTS : Afriplex TM GRT significantly reduced cell viability at 100 and 1000μg/mL after 48 hrs. Acute CCl 4 treatment significantly increased serum alanine aminotransferase in rats. The highest extract treatment of 300 mg/kg significantly elevated aspartate amino transferase. There was severe macro vesicular in the CCl 4 group whereas mild to moderate micro vesicular steatosis was seen in the 300 mg/kg Afriplex TM GRT treated group. Highest extract treatment significantly reduced NFkB expression on Western blot analysis. CONCLUSION : The beneficial effects of pharmaceutical grade Afriplex GRT TM are concentration and dosage based. Afriplex GRT TM exerts its beneficial effects via NFkB as demonstrated by the dose dependent reduction of NFkB on Western blot analysis. More work need to be done to explore the exact mechanism that occurs in the NFkB pathway.The SAMRC Research Capacity Development and the National Research Foundation for the Thuthuka Grant.https://www.elsevier.com/locate/toxrephj2022BiochemistryGeneticsMicrobiology and Plant Patholog

Model development for predicting in vitro bio-capacity of green rooibos extract based on composition for application as screening tool in quality control

CITATION: Viraragavan, A. et al. 2020. Model development for predicting in vitro bio-capacity of green rooibos extract based on composition for application as screening tool in quality control. Food & Function, 11:3084-3094. doi:10.1039/C9FO02480HThe original publication is available at http://pubs.rsc.org/en/Journals/Journal/FOMounting evidence of the ability of aspalathin to target underlying metabolic dysfunction relevant to the development or progression of obesity and type 2 diabetes created a market for green rooibos extract as a functional food ingredient. Aspalathin is the obvious choice as a chemical marker for extract standardisation and quality control, however, often the concentration of a single constituent of a complex mixture such as a plant extract is not directly related to its bio-capacity, i.e. the level of in vitro bioactivity effected in a cell system at a fixed concentration. Three solvents (hot water and two EtOH–water mixtures), previously shown to produce bioactive green rooibos extracts, were selected for extraction of different batches of rooibos plant material (n = 10). Bio-capacity of the extracts, tested at 10 μg ml−1, was evaluated in terms of glucose uptake by C2C12 and C3A cells and lipid accumulation in 3T3-L1 cells. The different solvents and inter-batch plant variation delivered extracts ranging in aspalathin content from 54.1 to 213.8 g kg−1. The extracts were further characterised in terms of other major flavonoids (n = 10) and an enolic phenylpyruvic acid glucoside, using HPLC-DAD. The 80% EtOH–water extracts, with the highest mean aspalathin content (170.9 g kg−1), had the highest mean bio-capacity in the respective assays. Despite this, no significant (P ≥ 0.05) correlation existed between aspalathin content and bio-capacity, while the orientin, isoorientin and vitexin content correlated moderately (r ≥ 0.487; P < 0.05) with increased glucose uptake by C2C12 cells. Various multivariate analysis methods were then applied with Evolution Program-Partial Least Squares (EP-PLS) resulting in models with the best predictive power. These EP-PLS models, based on all quantified compounds, predicted the bio-capacity of the extracts for the respective cell types with RMSECV values ≤ 11.5, confirming that a complement of compounds, and not aspalathin content alone, is needed to predict the in vitro bio-capacity of green rooibos extracts. Additionally, the composition of hot water infusions of different production batches of green rooibos (n = 29) at ‘cup-of-tea’ equivalence was determined to relate dietary supplementation with the extract to intake in the form of herbal tea.Publishers 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