Epigallocatechin gallate as a nutraceutical to potentially target the metabolic syndrome: novel insights into therapeutic effects beyond its antioxidant and anti-inflammatory properties.

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.

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.

A review of challenges and prospects of 3D cell-based culture models used for studying drug induced liver injury during early phases of drug development.

Drug-induced liver injury (DILI) is the leading cause of compound attrition during drug development. Over the years, a battery of in-vitro cell culture toxicity tests is being conducted to evaluate the toxicity of compounds prior to testing in laboratory animals. Two-dimensional (2D) in-vitro cell culture models are commonly used and have provided a great deal of knowledge; however, these models often fall short in mimicking natural structures of tissues in-vivo. Testing in humans is the most logical method, but unfortunately there are ethical limitations associated with human tests. To overcome these limitations better human-relevant, predictive models are required. The past decade has witnessed significant efforts towards the development of three-dimensional (3D) in-vitro cell culture models better mimicking in-vivo physiology. 3D cell culture has advantages in being representative of the interactions of cells in-vivo and when validated can act as an interphase between 2D cell culture models and in-vivo animal models. The current review seeks to provide an overview of the challenges that make biomarkers used for detection of DILI not to be sensitive enough during drug development and explore how 3D cell culture models can be used to address the gap with the current models.

Trends in Vaccine Completeness in Children Aged 0-23 Months in Cape Town, South Africa.

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.

Activated monocytes as a therapeutic target to attenuate vascular inflammation and lower cardiovascular disease-risk in patients with type 2 diabetes: A systematic review of preclinical and clinical studies.

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.

Clinical use of N-acetyl cysteine during liver transplantation: Implications of oxidative stress and inflammation as therapeutic targets.

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.

Capsaicin, its clinical significance in patients with painful diabetic neuropathy.

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.

Corrigendum: In vitro Characterization of Insulin-Producing ß-Cell Spheroids.

[This corrects the article DOI: 10.3389/fcell.2020.623889.].

Drug-Induced Liver Injury: Clinical Evidence of N-Acetyl Cysteine Protective Effects.

Oxidative stress is a key pathological feature implicated in both acute and chronic liver diseases, including drug-induced liver injury (DILI). The latter describes hepatic injury arising as a direct toxic effect of administered drugs or their metabolites. Although still underreported, DILI remains a significant cause of liver failure, especially in developed nations. Currently, it is understood that mitochondrial-generated oxidative stress and abnormalities in phase I/II metabolism, leading to glutathione (GSH) suppression, drive the onset of DILI. N-Acetyl cysteine (NAC) has attracted a lot of interest as a therapeutic agent against DILI because of its strong antioxidant properties, especially in relation to enhancing endogenous GSH content to counteract oxidative stress. Thus, in addition to updating information on the pathophysiological mechanisms implicated in oxidative-induced hepatic injury, the current review critically discusses clinical evidence on the protective effects of NAC against DILI, including the reduction of patient mortality. Besides injury caused by paracetamol, NAC can also improve liver function in relation to other forms of liver injury such as those induced by excessive alcohol intake. The implicated therapeutic mechanisms of NAC extend from enhancing hepatic GSH levels to reducing biomarkers of paracetamol toxicity such as keratin-18 and circulating caspase-cleaved cytokeratin-18. However, there is still lack of evidence confirming the benefits of using NAC in combination with other therapies in patients with DILI.

Curcumin supplementation improves biomarkers of oxidative stress and inflammation in conditions of obesity, type 2 diabetes and NAFLD: updating the status of clinical evidence.

Oxidative stress and inflammation remain the major complications implicated in the development and progression of metabolic complications, including obesity, type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). In fact, due to their abundant antioxidant and anti-inflammatory properties, there is a general interest in understanding the therapeutic effects of some major food-derived bioactive compounds like curcumin against diverse metabolic diseases. Hence, a systematic search, through prominent online databases such as MEDLINE, Scopus, and Google Scholar was done focusing on randomized controlled trials (RCTs) reporting on the impact of curcumin supplementation in individuals with diverse metabolic complications, including obesity, T2D and NAFLD. Summarized findings suggest that curcumin supplementation can significantly reduce blood glucose and triglycerides levels, including markers of liver function like alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in patients with T2D and NAFLD. Importantly, this effect was consistent with the reduction of predominant markers of oxidative stress and inflammation, such as the levels of malonaldehyde (MDA), tumor necrosis factor-alpha (TNF-α), high sensitivity C-reactive protein (hs-CRP) and monocyte chemoattractant protein-1 (MCP-1) in these patients. Although RCTs suggest that curcumin is beneficial in ameliorating some metabolic complications, future research is still necessary to enhance its absorption and bioavailability profile, while also optimizing the most effective therapeutic doses.

Vitamin K: A vital micronutrient with the cardioprotective potential against diabetes-associated complications.

Cardiovascular disease (CVD) remains the leading cause of mortality in patients with type 2 diabetes (T2D). The conventional therapies seem to offer minimal long-term cardioprotection against diabetes-related complications in patients living with T2D. There is a growing interest in understanding the therapeutic effects of food-derived bioactive compounds in protecting or managing these metabolic diseases. This includes uncovering the therapeutic potential of fat-soluble micronutrients such as vitamin K, which are abundantly found in green leafy vegetables. We searched the major electronic databases including PubMed, Web of Sciences, Scopus, Google Scholar and Science direct. The search retrieved randomized clinical trials and preclinical studies, reporting on the impact of vitamin K on CVD-related complications in T2D. The current review updates clinical evidence on the therapeutic benefits of vitamin K by attenuating CVD-risk factors such as blood lipid profiles, blood pressure, as well as markers of oxidative stress and inflammation in patients with T2D. Importantly, the summarized preclinical evidence provides a unique perspective into the pathophysiological mechanisms that could be targeted by vitamin K in the primary prevention of T2D-related complications. Lastly, this review further explores the controversies related to the cardioprotective effects of vitamin K, and also provides the basic information such as the source and bioavailability profile of this micronutrient is covered to highlight its therapeutic potential.

In vitro Characterization of Insulin-Producing ß-Cell Spheroids.

Over the years, immortalized rodent ß-cell lines such as RIN, HIT, MIN, ßTC, and INS-1 have been used to investigate pancreatic ß-cell physiology using conventional two-dimensional (2D) culture techniques. However, physical and physiological limitations inherent to 2D cell culture necessitates confirmatory follow up studies using sentient animals. Three-dimensional (3D) culture models are gaining popularity for their recapitulation of key features of in vivo organ physiology, and thus could pose as potential surrogates for animal experiments. In this study, we aimed to develop and characterize a rat insulinoma INS-1 3D spheroid model to compare with 2D monolayers of the same cell line. Ultrastructural verification was done by transmission electron microscopy and toluidine blue staining, which showed that both 2D monolayers and 3D spheroids contained highly granulated cells with ultrastructural features synonymous with mature pancreatic ß-cells, with increased prominence of these features observed in 3D spheroids. Viability, as assessed by cellular ATP quantification, size profiling and glucose utilization, showed that our spheroids remained viable for the experimental period of 30 days, compared to the limiting 5-day passage period of INS-1 monolayers. In fact, increasing ATP content together with spheroid size was observed over time, without adverse changes in glucose utilization. Additionally, ß-cell function, assessed by determining insulin and amylin secretion, showed that the 3D spheroids retained glucose sensing and insulin secretory capability, that was more acute when compared to 2D monolayer cultures. Thus, we were able to successfully demonstrate that our in vitro INS-1 ß-cell 3D spheroid model exhibits in vivo tissue-like structural features with extended viability and lifespan. This offers enhanced predictive capacity of the model in the study of metabolic disease, ß-cell pathophysiology and the potential treatment thereof.

Popular three-dimensional models: Advantages for cancer, Alzheimer's and cardiovascular diseases.

The increasing prevalence of non-communicable diseases, namely cancer, Alzheimer's (AD) and cardiovascular diseases (CVDs), worldwide continues to be a major health burden. Research attempts have been made to understand the pathophysiology and develop effective therapeutic agents for these diseases using conventional in vitro and ex vivo models. Due to the complexity of human disease mechanisms, often these models fail to recapitulate clinically relevant pathologies. As such, interests are arising in the exploration of three-dimensional (3D) in-vitro models, which create an artificial environment to closely mimic in vivo human conditions. Several studies have developed 3D models for cancer, AD and CVD research which can greatly improve the understanding of biological mechanisms and mirror clinical drug activities. Thus, 3D cultures may provide new in-vitro models that recapitulate the architecture and biological mechanisms of human diseases prior to the need for the use of sentient animals.

Intestinal transport and absorption of bioactive phenolic compounds from a chemically characterized aqueous extract of Athrixia phylicoides.

ETHNOPHARMACOLOGICAL RELEVANCE: Athrixia phylicoides, popularly known as "bush tea", is an indigenous aromatic shrub found in mountainous and grassland areas of the northern and eastern parts of southern Africa. The plant is traditionally used for the treatment of several ailments, including coughing, treating infected wounds, treating boils and sore throat, hypertension and heart disease. Potential anti-diabetic effects have also been demonstrated in vitro. AIM OF THE STUDY: To investigate the intestinal transport of prominent phenolic constituents, across a fully differentiated Caco-2 monolayer, using a characterized aqueous extract of A. phylicoides, previously shown to have bioactivity. MATERIALS AND METHODS: HPLC-DAD and LC/MS analyses were used to identify the major phenolic compounds within the extract. Intestinal transport of the phenolic compounds was assessed using a differentiated Caco-2 monolayer model in order to predict bioavailability and identify metabolite formation. Rate of transport, efflux and percentage cross-over were calculated for the respective phenolic compounds. RESULTS: Nine prominent compounds, present in the aqueous extract of A. phylicoides, were identified. Of these, three phenolic acids (protocatechuic acid, caffeic acid and para-coumaric acid), crossed the Caco-2 cell monolayer in significant amounts, with Papp values of 4.52, 4.35 (×10-6cm/s) and 2.38 (×10-5cm/s), respectively. para-Coumaric acid was shown to have the highest predicted bioavailability. CONCLUSIONS: Para-Coumaric acid, identified for the first time in A. phylicoides, was shown to have the highest predicted bioavailability suggesting that it could play a major role in the bioactivity of A. phylicoides.