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Objective: This study investigated the prevalence trends of metabolic syndrome (MetS) in children and adolescents with obesity by systematically analyzing global data. Additionally, it aimed to compare regional disparities and criteria used to identify at-risk subpopulations among this demographic group., Methods: We searched three major databases, i.e., PubMed-Medline, Scopus, and Web of Science, from inception to August 31, 2023, yielding 2432 articles. We included original research papers reporting MetS prevalence among children and adolescents with obesity, irrespective of their regions and MetS diagnostic criteria used. We aggregated prevalence estimates using random-effects models to obtain the overall prevalence and conducted subgroup analyses for MetS criteria and study regions., Results: We included 57 studies, amounting to 27,923 participants. The overall prevalence of MetS in participants with obesity varied greatly across studies, ranging from 2.1% to 74.4%, with an average prevalence of 29.4%. This high prevalence of MetS was further supported by a meta-analysis comprising 57 studies that further strengthened the observation of a high prevalence of MetS, revealing an overall prevalence of 26% (95% CI: 0.22-0.30; I 2  = 98%)., Conclusions: Children and adolescents with obesity face a heightened risk of developing MetS. There is a pressing need for heightened attention to this issue, particularly in low- and middle-income countries such as those in sub-Saharan Africa., (© 2024 The Obesity Society.)

Background: Neuregulin 4 (Nrg4) is a brown adipose tissue-derived adipokine that greatly affects systemic metabolism and improves metabolic derangements. Although abnormal circulating levels of Nrg4 are common in obesity, it remains elusive whether low or elevated levels of this batokine are associated with the onset of metabolic diseases., Aim: To assess Nrg4 levels and its role as a feasible biomarker to predict the severity of obesity, gestational diabetes mellitus (GDM), type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and cardiovascular diseases (CVD)., Methods: A search for relevant studies was performed systematically using prominent search engines, including PubMed, Google Scholar, and Embase, by following PRISMA guidelines., Results: Ample clinical evidence reported low serum/plasma levels of Nrg4 in obesity and these were inversely proportional to the indices of metabolic syndrome, including body mass index, waist circumference, triglycerides, fasting plasma glucose, and homoeostatic model assessment for insulin resistance as well as high-sensitivity C-reactive protein. Low circulating Nrg4 levels may aid in the prediction of morbid obesity, and subsequent GDM, T2DM, NAFLD, and CVD., Conclusion: Current clinical evidence emphasizes that the circulating levels of Nrg4 are decreased in morbid obesity, and it also highlights that Nrg4 May serve as a potential prognostic biomarker for obesity-related metabolic diseases.

Objectives: There is a growing need to understand the potential role of soluble platelet selectin (sP-selectin) in sustained endothelial activation through increased levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion-1 (sVCAM-1) in people living with HIV (PLWH) on highly active antiretroviral therapy (HAART)., Methodology: This was a cross-sectional study involving PLWH on HAART (n = 55), in comparison to PLWH not on treatment (HAART-naïve) (n = 29), and (iii) HIV negative controls (n = 48) from the Mankweng area in the Limpopo province, South Africa. We quantified serum levels of sP-selectin, together with sICAM-1 and sVCAM-1. Most of the HAART-exposed group were on treatment for <5 years. We further performed frequency distribution and descriptive statistics for categorical variables., Results: Soluble P-selectin was positively correlated with sVCAM-1 (r = 0.469; p<0.001) in PLWH on HAART, even after adjusting for confounding factor such as age, BMI, and total cholesterol (r = 0.467; p<0.001). Moreover, in PLWH on HAART sP-selecting was independently associated with the release of sVCAM-1 (β = 0.445; p<0.001), even after adjusting for confounders (β = 0.475; p = 0.001). Serum levels of low-density lipoprotein cholesterol (LDL-C) (p = 0.004) and total cholesterol (p<0.001) were significantly higher in PLWH on HAART as compared to the HAART-naïve group., Conclusion: There is a need for more studies to investigate the role of sP-selectin in promoting endothelial activation and CVD-risk in PLWH on HAART, especially within the sub-Saharan Africa region., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mokoena et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Traditionally recognised as the energy reservoir and main site of adaptive thermogenesis, white and brown adipose tissues are complex endocrine organs regulating systemic energy metabolism via the secretion of bioactive molecules, termed "adipokines" and "batokines", respectively. Due to its significant role in regulating whole-body energy metabolism and other physiological processes, adipose tissue has been increasingly explored as a feasible therapeutic target for obesity. Flavonoids are one of the most significant plant polyphenolic compounds holding a great potential as therapeutic agents for combating obesity. However, understanding their mechanisms of action remains largely insufficient to formulate therapeutic theories. This review critically discusses scientific evidence highlighting the role of flavonoids in ameliorating obesity-related metabolic complications, including adipose tissue dysfunction, inflammation, insulin resistance, hepatic steatosis, and cardiovascular comorbidities in part by modulating the release of adipokines and batokines. Further discussion advocates for the use of therapeutics targeting these bioactive molecules as a potential avenue for developing effective treatment for obesity and its adverse metabolic diseases such as type 2 diabetes., Competing Interests: Conflict of interests The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Monitoring chronic diseases, particularly kidney disorders, in people living with HIV (PLWH) is of paramount importance. Here, a systematic search was conducted across electronic search engine and databases like PubMed, Scopus, and Google Scholar, from date of inception until December 2023, to identify pertinent studies reporting on any association between inflammation and kidney function in PLWH. Only six clinical studies in peer-reviewed journals met the inclusion criteria, involving 1467 participants aged 37 to 51, with approximately 17% being females. The report emphasizes the potential impact of highly active antiretroviral therapy (HAART) on kidney function in PLWH, highlighting the significance of monitoring inflammation markers as indicators of kidney function, even when HAART is effective. Acknowledging study limitations, particularly the scarcity of relevant research, the findings highlight a need for more research to inform on clinical guidance to optimize HIV management, particularly regarding kidney health and HAART regimens. Although very limited studies were evaluated, the study lays an important foundation for future research to uncover the complex relationship between HAART, inflammation markers, and kidney health in PLWH., (© 2024. The Author(s).)

Background: Limited evidence informs on the prevalence of chronic kidney disease (CKD) in people living with HIV (PLWH) in South Africa. Thus, this study aimed to determine the prevalence of CKD and its associated risk factors among PLWH within the rural province of Limpopo, South Africa., Methods: We conducted a cross-sectional study of 143 participants, subdivided into groups of PLWH ( n  = 103) and individuals without HIV ( n  = 43). Structured questionnaires were used to collect and capture sociodemographic information including age, sex, alcohol intake, smoking status, and educational status. Basic measurements taken included levels of cluster of differentiation 4 (CD4+) count, body mass index (BMI), blood pressure, plasma cystatin C, and fasting serum glucose levels. Plasma cystatin C-based estimated glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration (CKD-EPI) estimator to determine the prevalence of CKD., Results: The prevalence of CKD was approximately 7% in PLWH. Multivariate logistic regression analysis showed that it was only diabetes mellitus (odds ratio of 5.795, 95% confidence interval, p  = 0.034) and age (odds ratio of 1.078, 95% confidence interval, p  = 0.039) that were significantly associated with CKD in PLWH., Conclusion: Chronic kidney disease was prevalent in PLWH, and it was further associated with cardiovascular risk factors, diabetes, and ageing. As PLWH age, the burden of CKD may be increased with the increase in cardiovascular-related comorbidities such as diabetes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Choshi, Flepisi, Mabhida, Sekgala, Mokoena, Nkambule, Ndwandwe, Mchiza, Nqebelele, Kengne, Dludla and Hanser.)

Metabolic syndrome has emerged as a significant global public health concern, necessitating comprehensive examination alongside cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2D). This study provides a comprehensive analysis of clinical trials, drawing upon data sourced from the International Clinical Trials Registry Platform (ICTRP), until April 2023. Information pertaining to trial attributes and intervention features was gathered and subsequently summarized. Among the 2379 studies found on ICTRP from 18 clinical registries, ClinicalTrials.gov was the most popular with 55 % of the studies, based on data emerging from the United States. Most trials were for treatment (44 %) and prevention (17 %), with fewer focused on basic science, and diagnostic purposes. Diet and exercise were the most prominent, with 710 and 247 studies, respectively. Metformin and statins emerge as leading pharmacological therapies, reflecting the prevalence of CVD and T2D in the context of metabolic syndrome. However, there is growing recognition of other promising interventions, such as Glucagon-Like Peptide-1 agonists and Dipeptidyl Peptidase IV inhibitors, which offer potential in slowing the progression of metabolic syndrome-related conditions. Notably, clinical trials primarily assessed diagnostic markers like lipid profiles, insulin, and blood pressure, rather than body mass and body mass index. These parameters are crucial for evaluating the effectiveness and safety of interventions for metabolic syndrome due to its multi-condition nature. Most studies aimed to address general symptom relief, while highlighting a need for additional well-designed treatment trials with rigorous methodologies in accordance with the World Health Organization's guidance for consistent evaluation and treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Combined oral contraceptives (COCs) are known to cause weight gain and alter metabolic and immunological pathways. However, modifications in arterial or venous thrombotic risk profiles of women of reproductive ages on COC remain unclear. The study aimed at assessing the impact of COC on immune activation in diet-induced obesity. We further established whether the dietary intervention of switching from a high-fat diet (HFD) to a low-fat diet (LFD) attenuates immunological responses. Twenty (n=20) five-week-old female Sprague Dawley rats were randomly divided into two diet groups of HFD (n=15) and LFD (n=5) and were monitored for eight weeks. After eight weeks, animals in the HFD group switched diets to LFD and were randomly assigned to receive high-dose COC (HCOC) or low-dose COC (LCOC) for six weeks. Animals on HFD significantly gained weight and had a higher lee index when compared to the LFD group (p < 0.05). Moreover, the triglyceride-glucose index, insulin, and other metabolic parameters also increased in the HFD group compared to the LFD group (p < 0.001). Consistently, the levels of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α), were elevated in the HFD group when compared to the LFD group (p < 0.05). Upon switching from a high-fat to a low-fat diet, insulin levels persistently increased in animals receiving HCOC treatment compared to the LFD and HFD/LFD groups (p < 0.05). Thus, in a rat model of HFD-feeding, short-term HCOC treatment induces long-term metabolic dysregulation, which persists despite dietary intervention. However, further studies are recommended to confirm these findings., Competing Interests: Declaration of Competing Interest The authors declare no competing interest, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Combined oral contraceptives (COCs), use in individuals are associated with increased risk of thrombotic events. This highlights the significance of assessing the impact of COC on promoting coagulation and endothelial activation in high-fat diet (HFD)-fed Sprague Dawley rats., Methods: Twenty (20) five-weeks-old female Sprague Dawley rats weighing between 150 and 200g were subjected to both LFD and HFD-feeding for 8-weeks to determine its influence on basic metabolic status, hemostatic profile, hemodynamic parameters (blood pressure and heart rate), as well as selected biomarkers of coagulation (tissue factor and D-dimer) and endothelial activation (Von Willebrand factor and nitric oxide). Thereafter HFD-fed animals were treated with receive high dose combined oral contraceptive (HCOC) and low dose combine oral contraceptive (LCOC) for 6 weeks., Results: Our results showed that beyond weight gain, HFD-feeding was associated with hyperglycemia, increased mean arterial pressure, and reduced nitric oxide levels when compared with LFD group (p<0.05). Interestingly, treatment with high dose of COC for 6-weeks did not significantly alter atherothrombotic markers (p>0.05). However, this study is not without limitation as regulation of these markers remains to be confirmed within the cardiac tissues or endothelial cells of these animals., Conclusion: HFD-feeding orchestrate the concomitant release of pro-coagulants and endothelial activation markers in rats leading to haemostatic imbalance and endothelial dysfunction. Short-term treatment with COC shows no detrimental effects in these HFD-fed rats. Although in terms of clinical relevance, our findings depict the notion that the risk of CVD in association with COC may depend on the dosage and duration of use among other factors especially in certain conditions. However, additional studies are required to confirm these findings, especially long-term effects of this treatment within the cardiac tissues or endothelial cells of these animals in certain conditions relating to postmenopausal state., (Copyright © 2023 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.)

High-fat diet (HFD) feeding in rodents has become an essential tool to critically analyze and study the pathological effects of obesity, including mitochondrial dysfunction and insulin resistance. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) regulates cellular energy metabolism to influence insulin sensitivity, beyond its active role in stimulating mitochondrial biogenesis to facilitate skeletal muscle adaptations in response to HFD feeding. Here, some of the major electronic databases like PubMed, Embase, and Web of Science were accessed to update and critically discuss information on the potential role of PGC-1α during metabolic adaptations within the skeletal muscle in response to HFD feeding in rodents. In fact, available evidence suggests that partial exposure to HFD feeding (potentially during the early stages of disease development) is associated with impaired metabolic adaptations within the skeletal muscle, including mitochondrial dysfunction and reduced insulin sensitivity. In terms of implicated molecular mechanisms, these negative effects are partially associated with reduced activity of PGC-1α, together with the phosphorylation of protein kinase B and altered expression of genes involving nuclear respiratory factor 1 and mitochondrial transcription factor A within the skeletal muscle. Notably, metabolic abnormalities observed with chronic exposure to HFD (likely during the late stages of disease development) may potentially occur independently of PGC-1α regulation within the muscle of rodents. Summarized evidence suggests the causal relationship between PGC-1α regulation and effective modulations of mitochondrial biogenesis and metabolic flexibility during the different stages of disease development. It further indicates that prominent interventions like caloric restriction and physical exercise may affect PGC-1α regulation during effective modulation of metabolic processes., (© 2023. The Author(s).)

Chronic lymphocytic leukemia (CLL) is characterized by dysfunctional B cells. Immune checkpoint molecules such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death-1 (PD-1) are upregulated in patients with CLL and may correlate with prognostic markers such as beta-2 microglobulin (B2M). The aim of this study was to evaluate the levels of immune checkpoints on B cell subsets and to further correlate them with B2M levels in patients with CLL. We recruited 21 patients with CLL and 12 controls. B cell subsets and the levels of immune checkpoint expression were determined using conventional multi-color flow cytometry. Basal levels of B2M in patients with CLL were measured using an enzyme-linked immunosorbent assay. Patients with CLL had increased levels of activated B cells when compared to the control group, p < 0.001. The expression of PD-1 and CTLA-4 were increased on activated B cells and memory B cells, p < 0.05. There were no associations between B2M levels and the measured immune checkpoints on B cell subsets, after adjusting for sex and age. In our cohort, the patients with CLL expressed elevated levels of PD-1 and CTLA-4 immune checkpoints on activated and memory B cell subsets. However, there was no correlation between these immune checkpoint expressions and B2M levels.

Background: The use of combined oral contraceptive (COC) is common among women of reproductive age despite the potential risk of them developing thrombotic events. There is a need to understand how COC affects cardiorespiratory function and markers of immune activation in premenopausal women involved in exercise. This highlights a need for a systematic review to enhance our understanding of how the use of COC affects cardiovascular health in premenopausal women subjected to exercise., Method: This systematic review protocol was prepared following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) 2015 statement. An extensive search of relevant literature by two independent reviewers will be conducted through the EBSCOhost interface to access databases such as MEDLINE, EMBASE, and CINAHL. Other health sources, including Cochrane CENTRAL, unpublished studies and grey literature, will also be searched. The search will include all studies that report the effect of COC on essential parameters of cardiorespiratory function and markers of immune activation in premenopausal women involved in exercise. All included studies will be appraised using appraisal tools, while appropriate extraction tools will be used for data extraction. Where possible, eligible studies will be pooled for meta-analysis. If statistical pooling is not feasible, our findings will be presented in a narrative format. The certainty of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation Assessment (GRADE) tool., Trial Registration: PROSPERO registration number: CRD42021265257., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fabunmi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Despite the improved efficacy of highly active antiretroviral therapy (HAART) in viral suppression, emerging evidence indicates an increased burden of noncommunicable diseases in people living with HIV (PLWH). Immune activation and persistently elevated levels of inflammation have been associated with endothelial dysfunction in PLWH, likely contributing to the development of cardiovascular diseases (CVDs). Here, electronic search databases including PubMed, Google Scholar, Cochrane Library, and Science Direct were used to retrieve scientific evidence reporting on any association between markers of endothelial function and CVD-related outcomes in PLWH on HAART. Extracted data was subjected to quality assessment using the Downs and Black checklist. Most (60 %) of the results indicated the presence of endothelial dysfunction in PLWH on HAART, and this was mainly through reduced flow mediated dilation and elevated serum makers of adhesion molecules like ICAM-1, VCAM-1, and P-selectin. The summarized evidence indicates an association between persistently elevated markers of endothelial dysfunction and a pro-inflammatory state in PLWH on HAART. Only a few studies reported on improved endothelial function markers in PLWH on HAART, while limited evidence is available to prove that endothelial dysfunction is associated with CVD-risk, which could be attributed to therapeutic effects of HAART. Limited studies with relatively high quality of evidence were included in this systematic review. In conclusion, results from this review lay an important foundation for future research, even a meta-analysis, that will improve the understanding of the contributing factors to the burden of CVDs in PLWH on HAART., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Lipid overload or metabolic stress has gained popularity in research that explores pathological mechanisms that may drive enhanced oxidative myocardial damage. Here, H9c2 cardiomyoblasts were exposed to various doses of palmitic acid (0.06 to 1 mM) for either 4 or 24 h to study its potential physiological response to cardiac cells. Briefly, assays performed included metabolic activity, cholesterol content, mitochondrial respiration, and prominent markers of oxidative stress, as well as determining changes in mitochondrial potential, mitochondrial production of reactive oxygen species, and intracellular antioxidant levels like glutathione, glutathione peroxidase and superoxide dismutase. Cellular damage was probed using fluorescent stains, annexin V and propidium iodide. Our results indicated that prolonged exposure (24-hours) to palmitic acid doses ≥ 0.5 mM significantly impaired mitochondrial oxidative status, leading to enhanced mitochondrial membrane potential and increased mitochondrial ROS production. While palmitic acid dose of 1 mM appeared to induce prominent cardiomyoblasts damage, likely because of its capacity to increase cholesterol content/ lipid peroxidation and severely suppressing intracellular antioxidants. Interestingly, short-term (4-hours) exposure to palmitic acid, especially for lower doses (≤ 0.25 mM), could improve metabolic activity, mitochondrial function and protect against oxidative stress induced myocardial damage. Potentially suggesting that, depending on the dose consumed or duration of exposure, consumption of saturated fatty acids such as palmitic acid can differently affect the myocardium. However, these results are still preliminary, and in vivo research is required to understand the significance of maintaining intracellular antioxidants to protect against oxidative stress induced by lipid overload., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The pathological consequences of inflammation persist in people living with the human immunodeficiency virus (PLWH), regardless of the positive outcomes of highly active antiretroviral therapy (HAART). The current systematic review and meta-analysis aims to understand and explore the levels of high-sensitivity C-reactive protein (hs-CRP) and other cardiovascular disease (CVD)-risk factors including lipid profiles among PLWH on HAART. Major electronic databases including PubMed, Scopus, and Web of Science were searched to retrieve relevant global literature reporting on hs-CRP levels in PLWH on HAART. A total of twenty-two studies with an average participant age of 40 years were eligible for this systematic review and meta-analysis. Majority of the included studies were from Africa (n = 11), the United States (n = 6), and Europe (n = 5). Our systemic review showed that most studies reported increased levels of hs-CRP among PLWH on HAART when compared to controls (PLWH not on HAART or those without HIV), especially in studies from Africa. This was supported by a meta-analysis showing significantly elevated levels of hs-CRP in PLWH on HAART when compared to PLWH not on HAART (standardised mean difference [SMD] = 0.56; 95% CI = 0.10‑1.01, z = 2.41; p = 0.02) or those without HIV (SMD = 1.19; 95% CI = 0.76‑1.63, z = 5.35; p < 0.001). Where lipid profiles, as a major predictor for CVD risk, were also impaired in PLWH on HAART when compared to PLWH not on HAART and HIV-negative participants. In conclusion, elevated levels of hs-CRP and lipid levels are prevalent in PLWH on HAART, this may increase the risk of CVD complications, especially for those people living in Africa. However, more evidence in larger population studies is required to confirm these outcomes and unveil any possible clinical implications of HAART-induced modulation of hs-CRP levels in PLWH., (© 2024. The Author(s).)

Epigallocatechin gallate (EGCG) is one of the most abundant and powerful flavonoids contained in green tea. Because of the global increase in green tea consumption, there has been a general interest in understanding its health benefits, including its bioactive compounds like EGCG. Indeed, preclinical evidence already indicates that EGCG demonstrated a strong antioxidant and anti-inflammatory properties that could be essential in protecting against metabolic syndrome. The current review explores clinical evidence reporting on the beneficial effects of EGCG supplementation in obese subjects or patients with diverse metabolic complications that include type 2 diabetes and cardiovascular disease. The discussion incorporates the impact of different formulations of EGCG, as well as the effective doses and treatment duration. Importantly, besides highlighting the potential use of EGCG as a nutraceutical, the current review also discusses crucial evidence related to its pharmaceutical development as an agent to hinder metabolic diseases, including its bioavailability and metabolism profile, as well as its well-known biological properties.

The discovery and rejuvenation of metabolically active brown adipose tissue (BAT) in adult humans have offered a new approach to treat obesity and metabolic diseases. Beyond its accomplished role in adaptive thermogenesis, BAT secretes signaling molecules known as "batokines", which are instrumental in regulating whole-body metabolism via autocrine, paracrine, and endocrine action. In addition to the intrinsic BAT metabolite-oxidizing activity, the endocrine functions of these molecules may help to explain the association between BAT activity and a healthy systemic metabolic profile. Herein, we review the evidence that underscores the significance of BAT-derived metabolites, especially highlighting their role in controlling physiological and metabolic processes involving thermogenesis, substrate metabolism, and other essential biological processes. The conversation extends to their capacity to enhance energy expenditure and mitigate features of obesity and its related metabolic complications. Thus, metabolites derived from BAT may provide new avenues for the discovery of metabolic health-promoting drugs with far-reaching impacts. This review aims to dissect the complexities of the secretory role of BAT in modulating local and systemic metabolism in metabolic health and disease., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: We have previously determined that the occurrence of missed vaccination opportunities in children in Cape Town, South Africa, is shaped by both individual and contextual factors. These factors present valuable openings for enhancing quality and implementing broader strategies to enhance the delivery of routine Immunisation services., Methods: Here, we are further reporting regional-level data on the coverage and factors influencing vaccination completion within a similar study population, based on extensive data analysis from the 2016 South African Demographic and Health Survey., Results and Discussion: The study reveals commendable vaccination coverage for most vaccines within recommended schedules, with high rates of initial vaccinations at birth and during the primary vaccination schedule. However, there are notable areas for improvement, particularly in ensuring complete coverage for the second measles vaccine and the 18-month vaccine. Socio-demographic factors also play a role, with maternal education and caregiver awareness campaigns showing the potential to positively influence vaccination completeness. This study emphasises the importance of timely vaccinations during the early months of life and underscores the need for interventions to maintain coverage as children age. Specific sub-districts, such as Tygerberg, may require targeted efforts to enhance vaccination completeness. Additionally, assessing caregiver knowledge about child vaccination is deemed vital, as it can impact vaccination decisions and adherence., Conclusions: The findings provide valuable insights for public health interventions in Cape Town, aimed at reducing the burden of vaccine-preventable diseases and ensuring the health of the region's youngest population.

Sarcopenia remains one of the major pathological features of type 2 diabetes (T2D), especially in older individuals. This condition describes gradual loss of muscle mass, strength, and function that reduces the overall vitality and fitness, leading to increased hospitalizations and even fatalities to those affected. Preclinical evidence indicates that dysregulated mitochondrial dynamics, together with impaired activity of the NADPH oxidase system, are the major sources of oxidative stress that drive skeletal muscle damage in T2D. While patients with T2D also display relatively higher levels of circulating inflammatory markers in the serum, including high sensitivity-C-reactive protein, interleukin-6, and tumor necrosis factor-α that are independently linked with the deterioration of muscle function and sarcopenia in T2D. In fact, beyond reporting on the pathological consequences of both oxidative stress and inflammation, the current review highlights the importance of strengthening intracellular antioxidant systems to preserve muscle mass, strength, and function in individuals with T2D., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2023 Elsevier Inc. All rights reserved.)

There is an increasing interest in the use of nutraceuticals and plant-derived bioactive compounds from foods for their potential health benefits. For example, as a major active ingredient found from cruciferous vegetables like broccoli, there has been growing interest in understanding the therapeutic effects of sulforaphane against diverse metabolic complications. The past decade has seen an extensive growth in literature reporting on the potential health benefits of sulforaphane to neutralize pathological consequences of oxidative stress and inflammation, which may be essential in protecting against diabetes-related complications. In fact, preclinical evidence summarized within this review supports an active role of sulforaphane in activating nuclear factor erythroid 2-related factor 2 or effectively modulating AMP-activated protein kinase to protect against diabetic complications, including diabetic cardiomyopathy, diabetic neuropathy, diabetic nephropathy, as well as other metabolic complications involving non-alcoholic fatty liver disease and skeletal muscle insulin resistance. With clinical evidence suggesting that foods rich in sulforaphane like broccoli can improve the metabolic status and lower cardiovascular disease risk by reducing biomarkers of oxidative stress and inflammation in patients with type 2 diabetes. This information remains essential in determining the therapeutic value of sulforaphane or its potential use as a nutraceutical to manage diabetes and its related complications. Finally, this review discusses essential information on the bioavailability profile of sulforaphane, while also covering information on the pathological consequences of oxidative stress and inflammation that drive the development and progression of diabetes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The consumption of food-derived products, including the regular intake of pepper, is increasingly evaluated for its potential benefits in protecting against diverse metabolic complications. The current study made use of prominent electronic databases including PubMed, Google Scholar, and Scopus to retrieve clinical evidence linking the intake of black and red pepper with the amelioration of metabolic complications. The findings summarize evidence supporting the beneficial effects of black pepper ( Piper nigrum L.), including its active ingredient, piperine, in improving blood lipid profiles, including reducing circulating levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides in overweight and obese individuals. The intake of piperine was also linked with enhanced antioxidant and anti-inflammatory properties by increasing serum levels of superoxide dismutase while reducing those of malonaldehyde and C-reactive protein in individuals with metabolic syndrome. Evidence summarized in the current review also indicates that red pepper ( Capsicum annum ), together with its active ingredient, capsaicin, could promote energy expenditure, including limiting energy intake, which is likely to contribute to reduced fat mass in overweight and obese individuals. Emerging clinical evidence also indicates that pepper may be beneficial in alleviating complications linked with other chronic conditions, including osteoarthritis, oropharyngeal dysphagia, digestion, hemodialysis, and neuromuscular fatigue. Notably, the beneficial effects of pepper or its active ingredients appear to be more pronounced when used in combination with other bioactive compounds. The current review also covers essential information on the metabolism and bioavailability profiles of both pepper species and their main active ingredients, which are all necessary to understand their potential beneficial effects against metabolic diseases.

Cardiovascular diseases (CVDs) are considered the predominant cause of death globally. An abnormal increase in biomarkers of oxidative stress and inflammation are consistently linked with the development and even progression of metabolic diseases, including enhanced CVD risk. Coffee is considered one of the most consumed beverages in the world, while reviewed evidence regarding its capacity to modulate biomarkers of oxidative stress and inflammation remains limited. The current study made use of prominent electronic databases, including PubMed, Google Scholar, and Scopus to retrieve information from randomized controlled trials reporting on any association between coffee consumption and modulation of biomarkers of oxidative stress and inflammation in healthy individuals or those at increased risk of developing CVD. In fact, summarized evidence indicates that coffee consumption, mainly due to its abundant antioxidant properties, can reduce biomarkers of oxidative stress and inflammation, which can be essential in alleviating the CVD risk in healthy individuals. However, more evidence suggests that regular/prolonged use or long term (>4 weeks) consumption of coffee appeared to be more beneficial in comparison with short-term intake (<4 weeks). These positive effects are also observed in individuals already presenting with increased CVD risk, although such evidence is very limited. The current analysis of data highlights the importance of understanding how coffee consumption can be beneficial in strengthening intracellular antioxidants to alleviate pathological features of oxidative stress and inflammation to reduce CVD risk within the general population. Also covered within the review is essential information on the metabolism and bioavailability profile of coffee, especially caffeine as one of its major bioactive compounds.

Aflatoxin B1 is a secondary metabolite with a potentially devastating effect in causing liver damage in broiler chickens, and this is mainly facilitated through the generation of oxidative stress and malonaldehyde build-up. In the past few years, significant progress has been made in controlling the invasion of aflatoxins. Phytochemicals are some of the commonly used molecules endowed with potential therapeutic effects to ameliorate aflatoxin, by inhibiting the production of reactive oxygen species and enhancing intracellular antioxidant enzymes. Experimental models involving cell cultures and broiler chickens exposed to aflatoxin or contaminated diet have been used to investigate the ameliorative effects of phytochemicals against aflatoxin toxicity. Electronic databases such as PubMed, Science Direct, and Google Scholar were used to identify relevant data sources. The retrieved information reported on the link between aflatoxin B1-included cytotoxicity and the ameliorative potential/role of phytochemicals in chickens. Importantly, retrieved data showed that phytochemicals may potentially protect against aflatoxin B1-induced cytotoxicity by ameliorating oxidative stress and enhancing intracellular antioxidants. Preclinical data indicate that activation of nuclear factor erythroid 2-related factor 2 (Nrf2), together with its downstream antioxidant genes, may be a potential therapeutic mechanism by which phytochemicals neutralize oxidative stress. This highlights the need for more research to determine whether phytochemicals can be considered a useful therapeutic intervention in controlling mycotoxins to improve broiler health and productivity.

Background: The use of oral contraceptives (OCs) is associated with an increased risk of cardiovascular events such as arterial and venous thrombosis (VTE). Cardiovascular diseases (CVDs) are the leading cause of death worldwide, with low- and middle-income nations accounting for over three-quarter of CVD deaths. The aim of this systematic review is to provide a comprehensive synthesis of the available evidence on the link between OC use and CVD risk in premenopausal women and to further assess the role of geographic disparities in the reported prevalence of CVD risk in women on OCs., Methods: A comprehensive search of databases such as MEDLINE, Academic Search Complete, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Health Source: Nursing/Academic Edition was conducted, right from the inception to the present, by using the EBSCOhost search engine. The Cochrane Central Register of Clinical trials (CENTRAL) was also searched to augment relevant sources of information. OpenGrey, which is a repository of information providing open access to bibliographical references, was searched and the reference list of the selected studies was also scanned. The potential risk of bias of the included studies was assessed using the modified Downs and Black checklist. Data analysis was performed using the Review Manager (RevMan) version 5.3., Results: We included 25 studies that comprised 3,245 participants, of which 1,605 (49.5%) are OC users, while 1,640 (50.5%) are non-OC users. A total of 15 studies were included for meta-analysis, and the overall pooled estimates suggested a significant increase in the traditional cardiovascular risk variables [standardized mean difference (SMD) = 0.73, (0.46, 0.99) ( Z  = 5.41, p  < 0.001)] and little to no difference in endothelial activation among OC users when compared with non-OC users [SMD = -0.11, (-0.81, 0.60) ( Z  = 0.30, p  = 0.76)]. Europe [SMD = 0.03, (-0.21, 0.27), ( Z  = 0.25 p  = 0.88)] had the least effect size, while North America had the highest effect size [SMD = 1.86, (-0.31, 4.04), ( Z  = 1.68 p  = 0.09)] for CVD risk in OC users when compared with non-OC users., Conclusion: The use of OCs suggests a significant increase in the prevalence of traditional cardiovascular risk variables with little to no difference in the risk of endothelial dysfunction when compared with non-OC users, and the magnitude of CVD risks varies across different geographical regions., Registration and Protocol: This systematic review was registered in the international prospective register of systematic reviews (PROSPERO) under the registration number: CRD42020216169., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Fabunmi, Dludla and Nkambule.)

Poor adherence to the prescribed antihypertensive therapy is an understated public health problem and is one of the main causes of the high prevalence of uncontrolled hypertension in sub-Saharan Africa. Medication adherence is vital for the effectiveness of antihypertensive treatment and is key to ameliorating the clinical outcomes in hypertensive patients. However, it has often been ignored because the current methods used to assess medication adherence are not reliable, limiting their utilization in clinical practice. Therefore, the identification of the most accurate and clinically feasible method for measuring medication adherence is critical for tailoring effective strategies to improve medication adherence and consequently achieve blood pressure goals. This review not only explores various available methods for estimating medication adherence but also proposes therapeutic drug monitoring in hair for the measurement of medication adherence to the antihypertensive medication period., Competing Interests: The authors declare no conflict of interest. The content of the paper was exclusively written by the author(s) listed. No ghost writer was used to write this article., (Copyright: © 2023 The Author(s).)

Insulin resistance and pancreatic β-cell dysfunction are major pathological mechanisms implicated in the development and progression of type 2 diabetes (T2D). Beyond the detrimental effects of insulin resistance, inflammation and oxidative stress have emerged as critical features of T2D that define β-cell dysfunction. Predominant markers of inflammation such as C-reactive protein, tumor necrosis factor alpha, and interleukin-1β are consistently associated with β-cell failure in preclinical models and in people with T2D. Similarly, important markers of oxidative stress, such as increased reactive oxygen species and depleted intracellular antioxidants, are consistent with pancreatic β-cell damage in conditions of T2D. Such effects illustrate a pathological relationship between an abnormal inflammatory response and generation of oxidative stress during the progression of T2D. The current review explores preclinical and clinical research on the patho-logical implications of inflammation and oxidative stress during the development of β-cell dysfunction in T2D. Moreover, important molecular mechanisms and relevant biomarkers involved in this process are discussed to divulge a pathological link between inflammation and oxidative stress during β-cell failure in T2D. Underpinning the clinical relevance of the review, a systematic analysis of evidence from randomized controlled trials is covered, on the potential therapeutic effects of some commonly used antidiabetic agents in modulating inflammatory makers to improve β-cell function., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Brown adipose tissue (BAT), a thermoregulatory organ known to promote energy expenditure, has been extensively studied as a potential avenue to combat obesity. Although BAT is the opposite of white adipose tissue (WAT) which is responsible for energy storage, BAT shares thermogenic capacity with beige adipose tissue that emerges from WAT depots. This is unsurprising as both BAT and beige adipose tissue display a huge difference from WAT in terms of their secretory profile and physiological role. In obesity, the content of BAT and beige adipose tissue declines as these tissues acquire the WAT characteristics via the process called "whitening". This process has been rarely explored for its implication in obesity, whether it contributes to or exacerbates obesity. Emerging research has demonstrated that BAT/beige adipose tissue whitening is a sophisticated metabolic complication of obesity that is linked to multiple factors. The current review provides clarification on the influence of various factors such as diet, age, genetics, thermoneutrality, and chemical exposure on BAT/beige adipose tissue whitening. Moreover, the defects and mechanisms that underpin the whitening are described. Notably, the BAT/beige adipose tissue whitening can be marked by the accumulation of large unilocular lipid droplets, mitochondrial degeneration, and collapsed thermogenic capacity, by the virtue of mitochondrial dysfunction, devascularization, autophagy, and inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ziqubu, Dludla, Mthembu, Nkambule, Mabhida, Jack, Nyambuya and Mazibuko-Mbeje.)

Cardiovascular diseases (CVDs) continue to be the leading cause of death in people with diabetes mellitus. Severely suppressed intracellular antioxidant defenses, including low plasma glutathione (GSH) levels, are consistently linked with the pathological features of diabetes such as oxidative stress and inflammation. In fact, it has already been established that low plasma GSH levels are associated with increased risk of CVD in people with diabetes. Dietary supplements are widely used and may offer therapeutic benefits for people with diabetes at an increased risk of developing CVDs. However, such information remains to be thoroughly scrutinized. Hence, the current systematic review explored prominent search engines, including PubMed and Google Scholar, for updated literature from randomized clinical trials reporting on the effects of dietary supplements on plasma GSH levels in people with diabetes. Available evidence indicates that dietary supplements, such as coenzyme Q 10 , selenium, curcumin, omega-3 fatty acids, and vitamin E or D, may potentially improve cardiometabolic health in patients with diabetes. Such beneficial effects are related to enhancing plasma GSH levels and reducing cholesterol, including biomarkers of oxidative stress and inflammation. However, available evidence is very limited and additional clinical studies are still required to validate these findings, including resolving issues related to the bioavailability of these bioactive compounds.

Brown adipose tissue (BAT) is increasingly recognized as the major therapeutic target to promote energy expenditure and ameliorate diverse metabolic complications. There is a general interest in understanding the pleiotropic effects of metformin against metabolic complications. Major electronic databases and search engines such as PubMed/MEDLINE, Google Scholar, and the Cochrane library were used to retrieve and critically discuss evidence reporting on the impact of metformin on regulating BAT thermogenic activity to ameliorate complications linked with obesity. The summarized evidence suggests that metformin can reduce body weight, enhance insulin sensitivity, and improve glucose metabolism by promoting BAT thermogenic activity in preclinical models of obesity. Notably, this anti-diabetic agent can affect the expression of major thermogenic transcriptional factors such as uncoupling protein 1 (UCP1), nuclear respiratory factor 1 (NRF1), and peroxisome-proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α) to improve BAT mitochondrial function and promote energy expenditure. Interestingly, vital molecular markers involved in glucose metabolism and energy regulation such as AMP-activated protein kinase (AMPK) and fibroblast growth factor 21 (FGF21) are similarly upregulated by metformin treatment in preclinical models of obesity. The current review also discusses the clinical relevance of BAT and thermogenesis as therapeutic targets. This review explored critical components including effective dosage and appropriate intervention period, consistent with the beneficial effects of metformin against obesity-associated complications.

Introduction: The use of oral contraceptives (OCs) is linked to an increased risk of cardiovascular diseases (CVDs) in women of reproductive age. CVD remain one of the top causes of death worldwide, with at least three-quarters of deaths occurring in low-income and middle-income nations. The impact of various types of combined oral contraceptive (COC) on several modifiable risk factors associated with CVDs in premenopausal women is inconsistent regardless of genetic mutations. The aim of this systematic review will be to provide a comprehensive synthesis of the available evidence on the impact of COC usage on modifiable risk factors associated with CVDs and assess ethnic and geographic disparities in the reported prevalence of CVD., Methods and Analysis: This systematic review protocol was prepared in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses Protocols 2015 statement. An extensive search on the Embase, MEDLINE and Cochrane Library will be conducted from inception until. Two reviewers will independently screen for eligible studies using a predefined criterion. The risk of bias and quality of included studies will be assessed using the modified Downs and Black's checklist. Whereas the overall quality of included studies will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation assessment tool., Ethics and Dissemination: This is a review of existing studies and will not require ethical approval. The findings will be disseminated through peer-reviewed publication. The use of OC and the risk of CVDs including arterial and venous thrombosis remain a major concern among women of reproductive age. Thus, given the impact of COCs on the risk variables linked with CVDs, this review may provide an insight and assistance during COC use., Prospero Registration Number: CRD42020216169., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Unlike the white adipose tissue (WAT) which mainly stores excess energy as fat, brown adipose tissue (BAT) has become physiologically important and therapeutically relevant for its prominent role in regulating energy metabolism. The current study makes use of an established animal model of type 2 diabetes (T2D) db/db mice to determine the effect of the disease progression on adipose tissue morphology and gene regulatory signatures. Results showed that WAT and BAT from db/db mice display a hypertrophied phenotype that is consistent with increased expression of the pro-inflammatory cytokine, tumor necrosis factor-alpha (Tnf-α). Moreover, BAT from both db/db and non-diabetic db/+ control mice displayed an age-related impairment in glucose homeostasis, inflammatory profile, and thermogenic regulation, as demonstrated by reduced expression of genes like glucose transporter (Glut-4), adiponectin (AdipoQ), and uncoupling protein 1 (Ucp-1). Importantly, gene expression of the batokines regulating sympathetic neurite outgrowth and vascularization, including bone morphogenic protein 8b (Bmp8b), fibroblast growth factor 21 (Fgf-21), neuregulin 4 (Nrg-4) were altered in BAT from db/db mice. Likewise, gene expression of meteorin-like (Metrnl), growth differentiation factor 15 (Gdt-15), and C-X-C motif chemokine-14 (Cxcl-14) regulating pro- and anti-inflammation were altered. This data provides some new insights into the pathophysiological mechanisms involved in BAT hypertrophy (or whitening) and the disturbances of batokines during the development and progression of T2D. However, these are only preliminary results as additional experiments are necessary to confirm these findings in other experimental models of T2D., Competing Interests: Declaration of competing interest The authors, Khanyisani Ziqubu, Phiwayinkosi V. Dludla, Marakiya T. Moetlediwa, Thembeka A. Nyawo, Carmen Pheiffer1, Babalwa U. Jack, Bongani B. Nkambule, Sithandiwe E. Mazibuko-Mbeje, hereby declare that they have no conflicts of interest to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Dyslipidemia is one of the major risk factors for the development of cardiovascular disease (CVD) in patients with type 2 diabetes (T2D). This metabolic anomality is implicated in the generation of oxidative stress, an inevitable process involved in destructive mechanisms leading to myocardial damage. Fortunately, commonly used drugs like statins can counteract the detrimental effects of dyslipidemia by lowering cholesterol to reduce CVD-risk in patients with T2D. Statins mainly function by blocking the production of cholesterol by targeting the mevalonate pathway. However, by blocking cholesterol synthesis, statins coincidently inhibit the synthesis of other essential isoprenoid intermediates of the mevalonate pathway like farnesyl pyrophosphate and coenzyme Q 10 (CoQ 10 ). The latter is by far the most important co-factor and co-enzyme required for efficient mitochondrial oxidative capacity, in addition to its robust antioxidant properties. In fact, supplementation with CoQ 10 has been found to be beneficial in ameliorating oxidative stress and improving blood flow in subjects with mild dyslipidemia.. Beyond discussing the destructive effects of oxidative stress in dyslipidemia-induced CVD-related complications, the current review brings a unique perspective in exploring the mevalonate pathway to block cholesterol synthesis while enhancing or maintaining CoQ 10  levels in conditions of dyslipidemia. Furthermore, this review disscusses the therapeutic potential of bioactive compounds in targeting the downstream of the mevalonate pathway, more importantly, their ability to block cholesterol while maintaining CoQ 10 biosynthesis to protect against the destructive complications of dyslipidemia., (Copyright © 2022 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Background: Due to contradicting findings on impact of statins on endothelial function in type 2 diabetes mellitus especially across the randomized controlled trials (RCTs). With this systematic review, we aim to evaluate whether the use of statins improves endothelial function in adults with type 2 diabetes. We will further highlight if these biomarkers are ideal therapeutic targets for risk for atherosclerosis and cardiovascular disease., Methods: This protocol was carried out according to the preferred reporting items for systematic review and meta-analysis protocols-2015 guideline. The online databases, such as MEDLINE, Scopus, and Web of Sciences, will be targeted using the medical subject heading terms (MeSH) and text words. The review will include clinical studies on the effect of statins on markers of endothelial function in type 2 diabetes. The Cochrane risk of bias guideline will be used to assess the quality and risk of bias. We are planning to use the grading of recommendation assessment, development, and evaluation approach to evaluate the strength and quality of evidence., Results: This study will not involve human samples and patient data; hence ethics approval will not be required. The findings will be presented in journal clubs and conferences and published in peer-reviewed journals., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Natural compounds may bear promising therapeutic benefits against metabolic diseases such as type 2 diabetes mellitus (T2DM), which are characterized by a state of insulin resistance and mitochondrial dysfunction. Here, we examined the cellular mechanisms by which aspalathin, a dihydrochalcone C-glucoside unique to rooibos, may ameliorate palmitate-induced insulin resistance and mitochondrial dysfunction in cultured C2C12 myotubules. This current study demonstrated that aspalathin remains effective in improving glucose uptake in insulin-resistant skeletal muscle cells, supported by the upregulation of insulin-dependent signaling that involves the activation of insulin receptor (IR) and direct phosphorylation of protein kinase B (AKT). Interestingly, aspalathin also improved mitochondrial respiration and function, which was evident by an increased expression of carnitine palmitoyltransferase 1 (Cpt1), fatty acid transport protein 1 (Fatp1), sirtuin 1 (Sirt1), nuclear respiratory factor 1 (Nrf1), and transcription factor A, mitochondrial (Tfam). Importantly, our results showed that aspalathin treatment was effective in ameliorating the devastating outcomes of insulin resistance and mitochondrial dysfunction that are linked with an undesired pro-inflammatory response, by reducing the levels of well-known pro-inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and protein kinase C-theta (PKC-theta). Thus, beyond improving glucose uptake and insulin signaling, the current study brings a new perspective in the therapeutic benefits of aspalathin in improving mitochondrial respiration and blocking inflammation to attenuate the detrimental effect of palmitate in skeletal muscle cells.

Lipid peroxidation, including its prominent byproducts such as malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE), has long been linked with worsened metabolic health in patients with type 2 diabetes (T2D). In fact, patients with T2D already display increased levels of lipids in circulation, including low-density lipoprotein-cholesterol and triglycerides, which are easily attacked by reactive oxygen molecules to give rise to lipid peroxidation. This process severely depletes intracellular antioxidants to cause excess generation of oxidative stress. This consequence mainly drives poor glycemic control and metabolic complications that are implicated in the development of cardiovascular disease. The current review explores the pathological relevance of elevated lipid peroxidation products in T2D, especially highlighting their potential role as biomarkers and therapeutic targets in disease severity. In addition, we briefly explain the implication of some prominent antioxidant enzymes/factors involved in the blockade of lipid peroxidation, including termination reactions that involve the effect of antioxidants, such as catalase, coenzyme Q 10 , glutathione peroxidase, and superoxide dismutase, as well as vitamins C and E.

Carboxylative enzymes are involved in many pathways and their regulation plays a crucial role in many of these pathways. In particular, γ-glutamylcarboxylase (GGCX) converts glutamate residues (Glu) into γ-carboxyglutamate (Gla) of the vitamin K-dependent proteins (VKDPs) activating them. VKDPs include at least 17 proteins involved in processes such as blood coagulation, blood vessels calcification, and bone mineralization. VKDPs are activated by the reduced form of vitamin K, naturally occurring as vitamin K1 (phylloquinone) and K2 (menaquinones, MKs). Among these, MK7 is the most efficient in terms of bioavailability and biological effect. Similarly to other trans isomers, it is produced by natural fermentation or chemically in both trans and cis. However, the efficacy of the biological effect of the different isomers and the impact on humans are unknown. Our study assessed carboxylative efficacy of trans and cis MK7 and compared it with other vitamin K isomers, evaluating both the expression of residues of carboxylated Gla-protein by western blot analysis and using a cell-free system to determine the GGCX activity by HPLC. Trans MK7H 2 showed a higher ability to carboxylate the 70 KDa GLA-protein, previously inhibited in vitro by warfarin treatment. However, cis MK7 also induced a carboxylation activity albeit of a small extent. The data were confirmed chromatographically, in which a slight carboxylative activity of cis MK7H 2 was demonstrated, comparable with both K1H 2 and oxidized trans MK7 but less than trans MK7H 2 . For the first time, a difference of biological activity between cis and trans configuration of menaquinone-7 has been reported., (© 2022 The Authors. BioFactors published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.)

Diabetic neuropathy is a risk factor for developing complications such as autonomic cardiovascular disease, osteoarthropathy, foot ulcers, and infections, which may be the direct cause of death. Even worse, patients plagued by this condition display painful neuropathic symptoms that are usually severe and frequently lead to depression, anxiety, and sleep disarrays, eventually leading to a poor quality of life. There is a general interest in evaluating the therapeutic properties of topical capsaicin cream as an effective agent for pain relief in these patients. As such, the current review makes use of major search engines like PubMed and Google Scholar, to bring an updated analysis of clinical studies reporting on the therapeutic effects of capsaicin in patients with painful diabetic neuropathy. In fact, most of the summarized literature indicates that topical capsaicin (0.075 %) cream, when applied to the painful areas for approximately 8 weeks, can reduce pain, which may lead to clinical improvements in walking, working, and sleeping in patients with painful diabetic neuropathy. The current review also discusses essential information on capsaicin, including its source, bioavailability profile, as well as treatment doses and duration, to highlight its therapeutic potential., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Moringa oleifera is one of the popular plants that have shown significant health benefits. Certainly, preclinical evidence (predominantly from animal models) summarized in the current review supports the beneficial effects of Moringa oleifera leaf extracts in combating the prominent characteristic features of diabetes mellitus. This includes effective control of blood glucose or insulin levels, enhancement of insulin tissue sensitivity, improvement of blood lipid profiles, and protecting against organ damage under sustained conditions of hyperglycemia. Interestingly, as major complications implicated in the progression of diabetes, including organ damage, Moringa oleifera leaf and seed extracts could efficiently block the detrimental effects of oxidative stress and inflammation in these preclinical models. Notably, these extracts (especially leaf extracts) showed enhanced effects in strengthening intracellular antioxidant defences like catalase, superoxide dismutase, and glutathione to lower lipid peroxidation products and reduce prominent pro-inflammatory markers such as tumor necrosis factor-α, interleukin (1L)-β, IL-6, monocyte chemoattractant protein-1 and nitric oxide synthase. From animal models of diabetes, the common and effective dose of leaf extracts of Moringa oleifera was 100-300 mg/kg, within the treatment duration of 2-8 weeks. Whereas supplementation with approximately 20 g leaf powder of Moringa oleifera for at least 2 weeks could improve postprandial blood glucose in subjects with prediabetes or diabetes. Although limited clinical studies have been conducted on the antidiabetic properties of Moringa oleifera , current findings provide an important platform for future research directed at developing this plant as a functional food to manage diabetic complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mthiyane, Dludla, Ziqubu, Mthembu, Muvhulawa, Hlengwa, Nkambule and Mazibuko-Mbeje.)

Background: Obesity is a major risk factor for atherosclerotic cardiovascular disease (ASCVD) and is associated with altered platelet function. The mean platelet volume (MPV) is a rapid measure of platelet activation and a prognostic marker in patients with cardiovascular disease. However, no meta-analysis on the association between MPV and obesity has been conducted, and the value of monitoring the MPV in patients with obesity remains unclear., Objective: To provide cumulative evidence on whether the mean platelet volume (MPV) is increased in individuals with obesity and to describe associations between the ASCVD-risk factors and the MPV in individuals with obesity., Methods: This meta-analysis was prepared following the Meta-analysis Of Observational Studies (MOOSE) guidelines. We searched the PubMed and Embase database from inception until the 31st of March 2021. Studies were included when they reported the mean platelet volume in individuals with obesity and provided a suitable non-obese comparator group. The risk of bias was independently assessed by two reviewers using the Newcastle-Ottawa scale. The primary outcome of the meta-analysis was the MPV, while we considered the atherosclerotic risk profiles as a secondary outcome., Results: We identified 178 citations through the PUBMED and 255 citations through EMBASE database search. In all, 13 studies met the inclusion criteria. Firstly, we report an increased mean platelet volume in individuals with obesity compared to non-obese individuals (MD 0.79; [95%CI: 0.42 to 1.16], I2 = 93.4%). Moreover, the reported increase in the MPV was inversely associated with the body mass index (Coefficient: -0.57, standard error (SE): 0.18, p < 0.001) and directly related to changes in triglyceride levels (Coefficient: 4.99, standard error (SE): 1.14, p < 0.001)., Conclusion: This meta-analysis and meta-regression showed an increased MPV in nondiabetic individuals living with obesity. Moreover, the MPV was associated with hypertriglyceridemia, an independent predictor of atherosclerotic cardiovascular disease. Overall, the findings suggest that MPV may be a valuable rapid marker for the monitoring and risk-stratification of individuals with obesity who may be at risk of developing cardiovascular disease., (© 2022. The Author(s).)

Skeletal muscle insulin resistance and mitochondrial dysfunction are some of the major pathological defects implicated in the development of type 2 diabetes (T2D). Therefore, it has become necessary to understand how common interventions such as physical exercise and caloric restriction affect metabolic function, including physiological processes that implicate skeletal muscle dysfunction within a state of T2D. This review critically discusses evidence on the impact of physical exercise and caloric restriction on markers of insulin resistance and mitochondrial dysfunction within the skeletal muscle of patients with T2D or related metabolic complications. Importantly, relevant information from clinical studies was acquired through a systematic approach targeting major electronic databases and search engines such as PubMed, Google Scholar, and Cochrane library. The reported evidence suggests that interventions like physical exercise and caloric restriction, within a duration of approximately 2 to 4 months, can improve insulin sensitivity, in part by targeting the phosphoinositide 3-kinases/protein kinase B pathway in patients with T2D. Furthermore, both physical exercise and caloric restriction can effectively modulate markers related to improved mitochondrial function and dynamics. This was consistent with an improved modulation of mitochondrial oxidative capacity and reduced production of reactive oxygen species in patients with T2D or related metabolic complications. However, such conclusions are based on limited evidence, additional clinical trials are required to better understand these interventions on pathological mechanisms of T2D and related abnormalities., (Copyright © 2022 Elsevier Inc. All rights reserved.)

It remains essential to decipher some of the pathological mechanisms that link obesity with deteriorating human health. Insulin resistance, due to enhanced free fatty acid substrate delivery, results in disrupted glucose homeostasis and altered mitochondrial oxidative capacity, which is a characteristic feature of an obese state. In fact, as a major site for regulating glucose homeostasis and energy production in response to insulin, the skeletal muscle has become an interesting target tissue to understand the impact of lipid overload on the development of insulin resistance and impaired mitochondrial respiratory function. In addition to systematically retrieving the discussed data, the current review brings an essential perspective in understanding the relevance of experimental models of lipid overload such as high fat diets in understanding the pathological link between insulin resistance and pathological changes in mitochondrial oxidative capacity. Importantly, inclusion of evidence from transgenic model highlights some of the unique molecular targets that are implicated in the development of insulin resistance and inefficient mitochondrial respiration processes within an obese state. Importantly, saturation with lipid products such as ceramides and diacylglycerols, especially within the skeletal muscle, appears to be instrumental in paving the path leading to worsening of metabolic complications. These metabolic consequences mostly interfere with the efficiency of the mitochondrial electron transport chain, leading to overproduction of toxic reactive oxygen species. Therefore, therapeutic agents that reverse the effects of lipid overload by improving insulin sensitivity and mitochondrial oxidative capacity are crucial for the management or even treatment of metabolic diseases., (Copyright © 2021 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

The current study aimed to determine the expression levels of caspase-3 in circulating innate lymphoid cell subtypes (ILCs) in a high-fat diet (HFD)-induced prediabetes mouse model. Another critical point was to assess the therapeutic effects of metformin and fluvastatin in modulating caspase-3 activation in ILCs within these HFD-fed mice. Prominent results showed that mice exposed to HFD for 14 weeks displayed impaired glucose tolerance that was accompanied by elevated levels of low-density lipoprotein cholesterol (LDL-c) and altered haematological profile as characterised by significantly increased concentrations of red blood cell count, white cell count and lymphocytes when compared to those fed a low-fat diet (LFD). Moreover, the expression of caspase-3 in ILC1 and ILC3 was significantly increased in the HFD groups in comparison to the LFD-fed group. Notably, six-week treatment with metformin and fluvastatin reduced the caspase-3 activation in ILC subtypes. The reduced caspase-3 activation in ILC1 was inversely associated with HDL-c levels following metformin treatment. Interestingly, the reduced caspase-3 activation in ILC3 was associated with lower total cholesterol following fluvastatin treatment in these HFD-fed mice. However, there were no differences in activation of caspase-3 on ILC2 or any association between caspase-3 activation and changes in body weight or fasting blood glucose. Thus, while HFD-feeding clearly modulates ILCs, potentially leading to pro-apoptotic mechanisms, metformin and fluvastatin may play a major role in protecting against such metabolic disturbances.

Chronic inflammation remains an essential complication in the pathogenesis and aggravation of metabolic diseases. There is a growing interest in the use of medicinal plants or food-derived bioactive compounds for their antioxidant and anti-inflammatory properties to improve metabolic function. For example, rutin, a flavonol derivative of quercetin that is found in several medicinal plants and food sources has displayed therapeutic benefits against diverse metabolic diseases. Here, we searched the major electronic databases and search engines such as PubMed/MEDLINE, Scopus and Google Scholar to systematically extract and critically discuss evidence reporting on the impact of rutin against metabolic diseases by affecting inflammation. In fact, available preclinical evidence suggests that rutin, through its strong antioxidant properties, can effectively ameliorate inflammation by reducing the levels of pro-inflammatory markers such as tumor necrosis factor-α, interleukin (IL)-6, cyclooxygenase-2, IL-1β, as well as blocking nuclear factor kappa B (NF-κB)/mitogen-activated protein kinase (MAPK) activation to improve metabolic function. Notably, although clinical data on the impact of rutin on inflammation is limited, food-derived sources rich in this flavonol such as Fagopyrum tataricum, Coffea arabica and Aspalathus linearis (rooibos) have shown promise in improving metabolic function, in part by reducing markers of oxidative stress and inflammation. However, additional studies are still required to confirm the therapeutic properties of rutin in a clinical setting, including the enhancement of it low bioavailability profile., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Currently, liver transplantation is considered as the definitive treatment option for individuals with complete liver failure. However, the detrimental effects of oxidative stress and inflammation remain the predominant feature that drives hepatic ischemia-reperfusion injury during liver transplantation. As such, therapeutic drugs that hinder oxidative stress and attenuate inflammation, have become ideal targets to curb liver injuries during transplantation. The current review analyses available clinical evidence on the importance of using N-acetyl cysteine (NAC) during liver transplantation. Thus, prominent online search engines such as PubMed and Google Scholar were accessed to retrieve literature from randomized clinical trials reporting on the use of NAC during liver transplantation. Overwhelming evidence suggests that established therapeutic properties of NAC, through enhancing endogenous antioxidants like glutathione to block oxidative stress and attenuate inflammation, remain essential to improve liver function in patients undergoing liver transportation. However, to the contrary, some clinical studies did not show any beneficial effects in patients receiving NAC during liver transplantation. Thus, such controversies, in addition to discussing the implications of oxidative stress and inflammation in relation to hepatic ischemia-reperfusion injury remain the major subject of the current review., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Emerging evidence suggests that epicardial fat thickness (EFT) may be a critical feature to understand cardiac health and determine the risk of heart failure. The current review critically assesses and discusses evidence on the efficiency of measuring EFT, in comparison to the well-known markers B-type natriuretic peptide (BNP) and its N-terminal fragment pro-B-type natriuretic peptide (NT-proBNP), as a prognostic and diagnostic approach in individuals with or at risk of heart failure. A systematic approach was undertaken to search major databases, PubMed, Scopus, Google Scholar and the Cochrane library to identify studies that quantified EFT and serum BNP/NT-proBNP levels in individuals with or at risk of heart failure. Twelve studies met the inclusion criteria and a total of 1983 participants were included in this systematic review. Evidence shows a clear association between increased EFT and elevated BNP/NT-proBNP levels in individuals with metabolic disease and suggests that both methods can be used for heart failure diagnosis and prognosis. However, due to the broad spectrum of challenges linked with measuring EFT, BNP/Pro-BNP is the predominant method used for heart failure diagnosis and prognosis in clinical practice. Nonetheless, measuring EFT provides a powerful and reproducible diagnostic tool for risk stratification and heart failure diagnosis and prognosis. Importantly, measuring EFT proves valuable to validate BNP/NT-proBNP levels to predict heart failure, especially due to its non-invasive nature., (© 2021. The Author(s).)

Low grade inflammation is associated with the progression of atherosclerosis. Patients with type 2 diabetes (T2D) have altered cholesterol levels, which are targeted by free radicals to promote lipid peroxidation. Elevated levels of monocyte-associated cytokines such as interleukin (IL)-6, monocyte chemoattractant protein 1 (MCP-1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and tumor necrosis factor-alpha (TNF-α), subsequently drive endothelial tissue injury. In fact, the levels of circulating platelet-monocyte aggregates in patients with T2D is a robust marker for atherosclerosis and a cardiovascular disease (CVD)-risk factor. To identify eligible studies, we searched the major online databases using PubMed and Google Scholar. The cumulative evidence synthesized in the current review suggests that, traditional therapies which include thiazolidinediones, statins and some calcium channel blockers can be useful in the primary prevention of atherosclerosis by inhibiting the formation of monocyte-derived microparticles, and pro-inflammatory cytokines such as IL-6, TNF-α, MCP-1, and NF-κB in patients with T2D. Future studies are needed to ascertain whether the combination of dietary interventions and glucose or lipid lowering agents can provide an enhanced cardioprotection in patients with T2D., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)