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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.
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Terapia Antirretroviral Altamente Activa , Biomarcadores , Infecciones por VIH , Inflamación , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Biomarcadores/sangre , Femenino , Adulto , Masculino , Persona de Mediana Edad , Enfermedades Renales , Fármacos Anti-VIH/uso terapéutico , Riñón/fisiopatologíaRESUMEN
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.
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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.
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Infecciones por VIH , Insuficiencia Renal Crónica , Población Rural , Humanos , Masculino , Femenino , Sudáfrica/epidemiología , Estudios Transversales , Factores de Riesgo , Insuficiencia Renal Crónica/epidemiología , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Prevalencia , Adulto , Persona de Mediana Edad , Población Rural/estadística & datos numéricos , Tasa de Filtración Glomerular , Encuestas y CuestionariosRESUMEN
The introduction of antiretroviral therapy (ART) has significantly prolonged the lifespan of people living with human immunodeficiency virus (PLWH). However, the sustained use of this drug regimen has also been associated with a cluster of metabolic anomalies, including renal toxicity, which can lead to the development of kidney diseases. In this study, we reviewed studies examining kidney disease in PLWH sourced from electronic databases such as PubMed/MEDLINE, Scopus, and Google Scholar, as well as gray literature. The narrative synthesis of data from these clinical studies demonstrated that the serum levels of cystatin C remained unchanged or were not affected in PLWH on ART, while the creatinine-based glomerular filtration rate (GFR) fluctuated. In fact, some of the included studies showed that the creatinine-based GFR was increased in PLWH taking tenofovir disoproxil fumarate-containing ART, perhaps indicating that the use of both cystatin C- and creatinine-based GFRs is vital to monitor the development of kidney disease in PLWH. Clinical data summarized within this study indicate the potential detrimental effects of tenofovir-based ART regimens in causing renal tubular injury, while highlighting the possible beneficial effects of dolutegravir-based ART on improving the kidney function in PLWH. However, the summarized literature remains limited, while further clinical studies are required to provide insights into the potential use of cystatin C as a biomarker for kidney disease in PLWH.
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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 = 0.101.01, z = 2.41; p = 0.02) or those without HIV (SMD = 1.19; 95% CI = 0.761.63, 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.
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Enfermedades Cardiovasculares , Infecciones por VIH , Humanos , Adulto , Terapia Antirretroviral Altamente Activa , Proteína C-Reactiva , VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/complicaciones , LípidosRESUMEN
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.
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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.
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Tejido Adiposo Pardo , Enfermedades Metabólicas , Humanos , Tejido Adiposo Pardo/metabolismo , Obesidad/metabolismo , Metabolismo Energético/fisiología , Enfermedades Metabólicas/metabolismo , Transducción de Señal , Termogénesis/fisiologíaRESUMEN
Insulin resistance and pancreatic ß-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 ß-cell dysfunction. Predominant markers of inflammation such as C-reactive protein, tumor necrosis factor alpha, and interleukin-1ß are consistently associated with ß-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 ß-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 ß-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 ß-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 ß-cell function.
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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.
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Tejido Adiposo Beige , Obesidad , Humanos , Regulación de la Temperatura Corporal , Metabolismo Energético , Transporte BiológicoRESUMEN
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 Q10, 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.
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Enfermedades Cardiovasculares , Diabetes Mellitus , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Suplementos Dietéticos , Antioxidantes/farmacología , Diabetes Mellitus/tratamiento farmacológico , Glutatión , Estrés Oxidativo , Enfermedades Cardiovasculares/etiología , Inflamación/tratamiento farmacológicoRESUMEN
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.
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Tejido Adiposo Pardo , Metformina , Humanos , Tejido Adiposo Pardo/metabolismo , Metformina/farmacología , Metformina/uso terapéutico , Metformina/metabolismo , Estudios de Factibilidad , Obesidad/metabolismo , Glucosa/metabolismo , Termogénesis , Metabolismo Energético , Proteína Desacopladora 1/metabolismo , Tejido Adiposo Blanco/metabolismoRESUMEN
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 Q10 (CoQ10). 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 CoQ10 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 CoQ10 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 CoQ10 biosynthesis to protect against the destructive complications of dyslipidemia.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Dislipidemias , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Ubiquinona/uso terapéutico , Ubiquinona/metabolismo , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Ácido Mevalónico , Colesterol , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/etiología , Dislipidemias/complicaciones , Dislipidemias/tratamiento farmacológicoRESUMEN
Background: Vitamin C is one of the most consumed dietary compounds and contains abundant antioxidant properties that could be essential in improving metabolic function. Thus, the current systematic review analyzed evidence on the beneficial effects of vitamin C intake on cardiovascular disease (CVD)-related outcomes in patients with diabetes or metabolic syndrome. Methods: To identify relevant randomized control trials (RCTs), a systematic search was run using prominent search engines like PubMed and Google Scholar, from beginning up to March 2022. The modified Black and Downs checklist was used to assess the quality of evidence. Results: Findings summarized in the current review favor the beneficial effects of vitamin C intake on improving basic metabolic parameters and lowering total cholesterol levels to reduce CVD-risk in subjects with type 2 diabetes or related metabolic diseases. Moreover, vitamin C intake could also reduce the predominant markers of inflammation and oxidative stress like C-reactive protein, interleukin-6, and malondialdehyde. Importantly, these positive outcomes were consistent with improved endothelial function or increased blood flow in these subjects. Predominantly effective doses were 1,000 mg/daily for 4 weeks up to 12 months. The included RCTs presented with the high quality of evidence. Conclusion: Clinical evidence on the beneficial effects of vitamin C intake or its impact on improving prominent markers of inflammation and oxidative stress in patients with diabetes is still limited. Thus, more RCTs are required to solidify these findings, which is essential to better manage diabetic patients at increased risk of developing CVD.
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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 Q10, glutathione peroxidase, and superoxide dismutase, as well as vitamins C and E.
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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.
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Diabetes Mellitus , Neuropatías Diabéticas , Administración Tópica , Capsaicina/efectos adversos , Diabetes Mellitus/tratamiento farmacológico , Humanos , Dolor/tratamiento farmacológico , Calidad de VidaRESUMEN
Aims: The current study sought to investigate the association between the methylenetetrahydrofolate reductase (MTHFR) variant (rs1801133) and the risk of developing hypertension (HTN) in an indigenous South African population. Methods: A total of 442 participants (hypertensive, n = 279 and non-hypertensive, n = 163) from the indigenous tribe residing in Mthatha, Eastern Cape (South Africa) were recruited. HTN was defined as a systolic (SBP) and diastolic blood pressure (DBP) of ≥130/80 mmHg following American Heart Association guidelines. The genotyping of MTHFR (rs1801133) was assessed using MassARRAY® System. Thereafter, the association between rs1801133 in various genetic models and HTN was determined by logistic regression model analysis. Furthermore, the interaction between rs1801133 and selected risk factors on HTN was performed using the open-source multifactor dimensionality reduction (MDR). Results: The low frequency of the T allele (5%) was also observed when compared with the C allele (95%) in both cases and controls. After adjusting for confounding factors (gender, smoking status, BMI, and blood glucose levels), there were no significant associations were observed between rs1801133 and the risk of HTN in all genetic models: genotypic (OR 0.75, 95% CI 0.29-1.95, p = 0.56), dominant (OR 0.86, 95% CI 0.35-2.16, p = 0.75), co-dominant (OR 1.33, 95% CI 0.51-3.48, p = 0.55) and allelic (OR 0.80, 95% CI 0.49-1.62, p = 0.70) in logistic regression analysis. However, a significant interaction was reported among rs1801133, age, and gender (p < 0.0001) with the risk of HTN. Conclusion: The present study reports on the lack of association between MTHFR (rs1801133) and the risk of HTN in an indigenous South African tribe. However, an interaction between gender, age, and rs1801133 was observed. Thus, future studies with a large sample size are required to further validate these findings.
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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.
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In this review, we have gathered and analyzed the available genetic evidence on the association between the methylenetetrahydrofolate reductase gene (MTHFR), rs1801133 and the risk of Hypertension (HTN) in African populations, which was further compared to the global data evidence. This review was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol and Human Genome Epidemiology Network (HuGENet) guidelines. Literature was retrieved through major search databases, including PubMed, Scopus, Web of Science, and African Journal Online. We identified 64 potential studies, of which 4 studies were from the African continent and 60 studies were reported globally. Among the studies conducted in Africa, only two (n = 2) reported a significant association between the MTHFR (rs1801133) and the risk of developing HTN. Only one (n = 1) study population was purely composed of black Africans, while others were of other ethnicities. Among studies conducted in other continents (n = 60), forty-seven (n = 47) studies reported a positive association between MTHFR (rs1801133) and the risk of developing HTN, whereas the remaining studies (n = 14) did not show a significant association. Available literature suggests an apparent association between rs1801133 and HTN in global regions; however, such information is still scarce in Africa, especially in the black African population.
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Hipertensión , Metilenotetrahidrofolato Reductasa (NADPH2) , Población Negra/genética , Predisposición Genética a la Enfermedad , Humanos , Hipertensión/epidemiología , Hipertensión/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
Hypertension (HTN) is a persistent public health problem affecting approximately 1.3 billion individuals globally. Treatment-resistant hypertension (TRH) is defined as high blood pressure (BP) in a hypertensive patient that remains above goal despite use of ≥3 antihypertensive agents of different classes including a diuretic. Despite a plethora of treatment options available, only 31.0% of individuals have their HTN controlled. Interindividual genetic variability to drug response might explain this disappointing outcome because of genetic polymorphisms. Additionally, the poor knowledge of pathophysiological mechanisms underlying hypertensive disease and the long-term interaction of antihypertensive drugs with blood pressure control mechanisms further aggravates the problem. Furthermore, in Africa, there is a paucity of pharmacogenomic data on the treatment of resistant hypertension. Therefore, identification of genetic signals having the potential to predict the response of a drug for a given individual in an African population has been the subject of intensive investigation. In this review, we aim to systematically extract and discuss African evidence on the genetic variation, and pharmacogenomics towards the treatment of HTN. Furthermore, in silico methods are utilized to elucidate biological processes that will aid in identifying novel drug targets for the treatment of resistant hypertension in an African population. To provide an expanded view of genetic variants associated with the development of HTN, this study was performed using publicly available databases such as PubMed, Scopus, Web of Science, African Journal Online, PharmGKB searching for relevant papers between 1984 and 2020. A total of 2784 articles were reviewed, and only 42 studies were included following the inclusion criteria. Twenty studies reported associations with HTN and genes such as AGT (rs699), ACE (rs1799752), NOS3 (rs1799983), MTHFR (rs1801133), AGTR1 (rs5186), while twenty-two studies did not show any association within the African population. Thereafter, an in silico predictive approach was utilized to identify several genes including CLCNKB, CYPB11B2, SH2B2, STK9, and TBX5 which may act as potential drug targets because they are involved in pathways known to influence blood pressure. Next, co-expressed genes were identified as they are controlled by the same transcriptional regulatory program and may potentially be more effective as multiple drug targets in the treatment regimens for HTN. Genes belonging to the co-expressed gene cluster, ACE, AGT, AGTR1, AGTR2, and NOS3 as well as CSK and ADRG1 showed enrichment of G-protein-coupled receptor activity, the classical targets of drug discovery, which mediate cellular signaling processes. The latter is of importance, as the targeting of co-regulatory gene clusters will allow for the development of more effective HTN drug targets that could decrease the prevalence of both controlled and TRH.
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Antihipertensivos/uso terapéutico , Población Negra/genética , Biología Computacional/métodos , Predisposición Genética a la Enfermedad , Hipertensión/epidemiología , Farmacogenética , Polimorfismo Genético , África/epidemiología , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/genética , Factores de RiesgoRESUMEN
Background: The occurrence of hypertension has been increasing alarmingly in both low and middle-income countries. Despite acknowledging hypertension as the most common life-threatening risk factor for cardiovascular disease (CVD), a dearth of data is available on the prevalence, awareness, and determinants of hypertension in rural parts of South Africa. The principal aim of the current study is to determine the prevalence and associated risk factors of hypertension among a black rural African population from the Mtatha town of Eastern Cape Province. Methods: This was a cross-sectional study, and individuals over 18 years of age were randomly screened using a World Health Organization stepwise questionnaire. Sociodemographic information, anthropometric measurements, fasting blood glucose levels, and three independent blood pressure (BP) readings were measured. Blood pressure measurements were classified according to the American Heart Association guidelines. Univariate and multivariate analyses were performed to determine the significant predictors of hypertension. Results: Of the total participants (n = 556), 71% of individuals had BP scores in the hypertensive range. In univariate analysis, age, westernized diet, education, income, and diabetic status, as well as overweight/obese status were positively associated with the prevalence of hypertension. However, in a multivariate logistic regression analysis only, age, body mass index (BMI), diabetic status, and westernized diet were significantly associated with a higher risk of developing hypertension. Gender, age, and BMI were potential factors having a significant association with the treatment of hypertension. Individuals who did not consider the importance of medicine had higher chances of having their hypertension being untreated. Conclusions: Prevalence of hypertension was high among the black rural African population of Mthatha town. Gender, age, westernized diet, education level, income status, diabetic as well as overweight/obese status were the most significant predictors of hypertension.