A systematic review assessing the association of inflammatory markers with kidney dysfunction in people living with HIV on highly active antiretroviral therapy.

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.

Global trends in clinical trials and interventions for the metabolic syndrome: A comprehensive analysis of the WHO International Clinical Trials platform.

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.

Aggravated Systemic Inflammation and Atherogenicity in African Patients Living With Type 2 Diabetes and Hypertension Comorbidity.

Objective: To explore routinely measured markers of systemic inflammation in hypertension (HTN) and type 2 diabetes (T2D) comorbidity, and their association with atherogenicity. Methods: This study included a total of 70 patients with T2D which were categorised into 2 groups, that is with T2D and with HTN comorbidity (T2D + HTN) (n = 35/group). All measured laboratory parameters were determined using standardised methods. Results: The neutrophil/lymphocyte ratio (NLR) was elevated in patients with T2D + HTN when compared to those with T2D (P = .0494). This was also the case with C-reactive protein (CRP) levels (P < .0001) and systemic immune-inflammation (SII) index (P = .0298). Notably, the majority of patients with T2D + HTN [63% (n = 22)] were classified as having an intermediate or high atherogenic index of plasma (AIP). The correlation analysis of systemic inflammation showed significant associations between CRP and age (r = .24, P = .0477); CRP and red blood cell count (r = -.4, P = .0455), and SII and systolic blood pressure (SBP) (r = .33, P = .0056). However, there was no association between inflammatory profiles and lipograms (P > .05). We further assessed predictors for an elevated AIP using mutivariable regression model adjusted for age, SBP, CRP and SII. Only NLR was a significant predictor of AIP (ß = .287, SE: 0.1, P = .0046). Conclusion: HTN comorbidity in T2D is associated with exacerbated levels of inflammation and atherogenicity. NLR is a significant independent risk factor for increased atherogenicity in patients with T2D. Therefore, the use of therapeutic strategies that target and alleviate inflammation in patients with T2D and HTN comorbidity is imperative in reducing the initiating and progression of cardiovascular events (CVEs).

Prevalence of chronic kidney disease and associated risk factors among people living with HIV in a rural population of Limpopo Province, South Africa.

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.

Factors that modulate platelet reactivity as measured by 5 assay platforms in 3429 individuals.

Background: Assessment of platelet function is key in diagnosing bleeding disorders and evaluating antiplatelet drug efficacy. However, there is a prevailing "one-size-fits-all" approach in the interpretation of measures of platelet reactivity, with arbitrary cutoffs often derived from healthy volunteer responses. Objectives: Our aim was to compare well-used platelet reactivity assays. Methods: Blood and platelet-rich plasma obtained from the Framingham Heart Study (N = 3429) were assayed using a range of agonists in 5 platelet assays: light transmission aggregometry, Optimul aggregometry, Multiplate impedance aggregometry (Roche Diagnostics), Total Thrombus-Formation Analysis System, and flow cytometry. Using linear mixed-effect models, we determined the contribution of preanalytical and technical factors that modulated platelet reactivity traits. Results: A strong intra-assay correlation of platelet traits was seen in all assays, particularly Multiplate velocity (r = 0.740; ristocetin vs arachidonic acid). In contrast, only moderate interassay correlations were observed (r = 0.375; adenosine diphosphate Optimul Emax vs light transmission aggregometry large area under the curve). As expected, antiplatelet drugs strongly reduced platelet responses, with aspirin use primarily targeting arachidonic acid-induced aggregation, and explained substantial variance (ß = -1.735; P = 4.59 × 10-780; variance proportion = 46.2%) and P2Y12 antagonists blocking adenosine diphosphate responses (ß = -1.612; P = 6.75 × 10-27; variance proportion = 2.1%). Notably, female sex and older age were associated with enhanced platelet reactivity. Fasting status and deviations from standard venipuncture practices did not alter platelet reactivity significantly. Finally, the agonist batch, phlebotomist, and assay technician (more so for assays that require additional sample manipulation) had a moderate to large effect on measured platelet reactivity. Conclusion: Caution must be exercised when extrapolating findings between assays, and the use of standard ranges must be medication-specific and sex-specific at a minimum. Researchers should also consider preanalytical and technical variables when designing experiments and interpreting platelet reactivity measures.

A systematic review assessing the potential use of cystatin c as a biomarker for kidney disease in people living with HIV on antiretroviral therapy.

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.

High-dose oral contraceptives induce hyperinsulinemia without altering immune activation in diet-induced obesity which persists even following a dietary low-fat diet intervention.

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.

Effect of combined oral contraceptive on cardiorespiratory function and immune activation in premenopausal women involved in exercise: A systematic review protocol.

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.

High-sensitivity C-reactive protein among people living with HIV on highly active antiretroviral therapy: a systemic review and meta-analysis.

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.

Low levels and partial exposure to palmitic acid improves mitochondrial function and the oxidative status of cultured cardiomyoblasts.

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.

Endothelial dysfunction and cardiovascular diseases in people living with HIV on specific highly active antiretroviral therapy regimen: A systematic review of clinical studies.

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.

Genetic and nongenetic drivers of platelet reactivity in healthy Tanzanian individuals.

BACKGROUND: Platelets play a key role in hemostasis, inflammation, and cardiovascular diseases. Platelet reactivity is highly variable between individuals. The drivers of this variability in populations from Sub-Saharan Africa remain largely unknown. OBJECTIVES: We aimed to investigate the nongenetic and genetic determinants of platelet reactivity in healthy adults living in a rapidly urbanizing area in Northern Tanzania. METHODS: Platelet activation and reactivity were measured by platelet P-selectin expression and the binding of fibrinogen in unstimulated blood and after ex vivo stimulation with adenosine diphosphate and PAR-1 and PAR-4 ligands. We then analyzed the associations of platelet parameters with host genetic and nongenetic factors, environmental factors, plasma inflammatory markers, and plasma metabolites. RESULTS: Only a few associations were found between platelet reactivity parameters and plasma inflammatory markers and nongenetic host and environmental factors. In contrast, untargeted plasma metabolomics revealed a large number of associations with food-derived metabolites, including phytochemicals that were previously reported to inhibit platelet reactivity. Genome-wide single-nucleotide polymorphism genotyping identified 2 novel single-nucleotide polymorphisms (rs903650 and rs4789332) that were associated with platelet reactivity at the genome-wide level (P < 5 × 10-8) as well as a number of variants in the PAR4 gene (F2RL3) that were associated with PAR4-induced reactivity. CONCLUSION: Our study uncovered factors that determine variation in platelet reactivity in a population in East Africa that is rapidly transitioning to an urban lifestyle, including the importance of genetic ancestry and the gradual abandoning of the traditional East African diet.

High-fat diet promotes coagulation and endothelial activation in Sprague Dawley rats: Short-term effects of combined oral contraceptives.

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.

Potential regulatory role of PGC-1α within the skeletal muscle during metabolic adaptations in response to high-fat diet feeding in animal models.

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.

Potential Benefits of Coffee Consumption on Improving Biomarkers of Oxidative Stress and Inflammation in Healthy Individuals and Those at Increased Risk of Cardiovascular Disease.

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.

Bioactive Properties, Bioavailability Profiles, and Clinical Evidence of the Potential Benefits of Black Pepper (Piper nigrum) and Red Pepper (Capsicum annum) against Diverse Metabolic Complications.

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.

Sarcopenia in a type 2 diabetic state: Reviewing literature on the pathological consequences of oxidative stress and inflammation beyond the neutralizing effect of intracellular antioxidants.

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.

Sulforaphane: A nutraceutical against diabetes-related complications.

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.

Trends among platelet function, arterial calcium, and vascular function measures.

Arterial tonometry and vascular calcification measures are useful in cardiovascular disease (CVD) risk assessment. Prior studies found associations between tonometry measures, arterial calcium, and CVD risk. Activated platelets release angiopoietin-1 and other factors, which may connect vascular structure and platelet function. We analyzed arterial tonometry, platelet function, aortic, thoracic and coronary calcium, and thoracic and abdominal aorta diameters measured in the Framingham Heart Study Gen3/NOS/OMNI-2 cohorts (n = 3,429, 53.7% women, mean age 54.4 years ±9.3). Platelet reactivity in whole blood or platelet-rich plasma was assessed using 5 assays and 7 agonists. We analyzed linear mixed effects models with platelet reactivity phenotypes as outcomes, adjusting for CVD risk factors and family structure. Higher arterial calcium trended with higher platelet reactivity, whereas larger aortic diameters trended with lower platelet reactivity. Characteristic impedance (Zc) and central pulse pressure positively trended with various platelet traits, while pulse wave velocity and Zc negatively trended with collagen, ADP, and epinephrine traits. All results did not pass a stringent multiple test correction threshold (p < 2.22e-04). The diameter trends were consistent with lower shear environments invoking less platelet reactivity. The vessel calcium trends were consistent with subclinical atherosclerosis and platelet activation being inter-related.

What is the context? Prior research has reported that measures of vascular system-influencing proteins such as angiopoietin-2, arterial calcium plaque formation, and arterial stiffness assessed by tonometry are associated with CVD risk.Since activated platelets produce and release vascular proteins like angiopoietin when activated, and microparticles that interact with endothelium, release of the foregoing mediators could provide one way in which vascular structure and platelet function influence each other.To our knowledge, no prior studies have directly investigated associations between these measures in a large sample. This investigation relates platelet function to arterial tonometry, aortic and arterial diameter, and arterial calcium measures in the Framingham Heart Study (FHS) Gen3/NOS/OMNI-2 cohorts (n = 3,429).What's new? Generally, higher arterial calcium measures trended with higher platelet reactivity, whereas larger aortic diameters trended with lower platelet reactivity.Arterial tonometry measures had positive and negative trends with platelet functions, including platelet measures with opposite relations to negative-inverse carotid-femoral pulse wave velocity (niCFPWV) and characteristic impedance (Zc). All tonometry, calcium, and diameter results did not reach a more stringent multiple testing threshold (p < 2.22e-04).What's the impact? The aortic diameter trends are consistent with lower shear stress invoking less platelet reactivity.The vessel calcium trends are consistent with increased vascular calcium buildup that could provoke platelet activation, thereby contributing to increased blood clot risk. Conversely, increased platelet activation could contribute to increased inflammation and thrombosis, leading to calcification in the arterial wall.

Alcohol intake including wine drinking is associated with decreased platelet reactivity in a large population sample.

BACKGROUND: Alcohol consumption is linked to decreased platelet function. Whether this link is dependent on sex or type of beverage remains unclear. METHODS: Cross-sectional data were obtained from the Framingham Heart Study (N = 3427). Alcohol consumption was assessed by using standardized medical history and Harvard semi-quantitative food frequency questionnaires. Five bioassays measured 120 platelet reactivity traits across agonists in whole-blood and platelet-rich plasma samples. Linear mixed-effects models adjusted for age, sex and aspirin use, hypertension, body mass index, cholesterol, high-density lipoprotein, triglycerides, smoking and diabetes evaluated associations between platelet reactivity and alcohol consumption. Beta effects, the regression coefficients that estimate the amount of change in each unit of the predictor variable whereas all other predictor variables remain fixed, for heavy alcohol consumption were compared with effects of aspirin use. RESULTS: Alcohol consumption was associated with decreased platelet reactivity, with more associations among wine and liquor compared with beer. Many platelet-alcohol associations in the full sample (86%, P < 0.01) had larger effect sizes in females. Lower light transmission aggregometry adenosine diphosphate (1.82 µM) maximum aggregation (P = 2.6E-3, 95% CI = -0.07, -0.02, ß = -0.042) and area under the curve (P = 7.7E-3, 95% CI = -0.07, -0.01, ß = -0.039) were associated with white wine consumption; however, red wine had no associations with platelet reactivity. The effect of aspirin use was on average 11.3 (±4.0) times greater than that of heavy drinking in our full sample. CONCLUSIONS: We confirm associations between alcohol consumption and decreased platelet reactivity. Effects appeared larger for liquor and wine intake and in our female cohort. Red wine consumption is not associated with lower platelet function, contrasting with prior population studies. Although we report an inhibitory relationship between alcohol intake and platelet function, these effects appear much smaller than that of aspirin use.