Natural products as novel anti-obesity agents: insights into mechanisms of action and potential for therapeutic management

Obesity affects more than 10% of the adult population globally. Despite the introduction of diverse medications aimed at combating fat accumulation and obesity, a significant number of these pharmaceutical interventions are linked to substantial occurrences of severe adverse events, occasionally leading to their withdrawal from the market. Natural products serve as attractive sources for anti-obesity agents as many of them can alter the host metabolic processes and maintain glucose homeostasis via metabolic and thermogenic stimulation, appetite regulation, pancreatic lipase and amylase inhibition, insulin sensitivity enhancing, adipogenesis inhibition and adipocyte apoptosis induction. In this review, we shed light on the biological processes that control energy balance and thermogenesis as well as metabolic pathways in white adipose tissue browning, we also highlight the anti-obesity potential of natural products with their mechanism of action. Based on previous findings, the crucial proteins and molecular pathways involved in adipose tissue browning and lipolysis induction are uncoupling protein-1, PR domain containing 16, and peroxisome proliferator-activated receptor-γ in addition to Sirtuin-1 and AMP-activated protein kinase pathway. Given that some phytochemicals can also lower proinflammatory substances like TNF-α, IL-6, and IL-1 secreted from adipose tissue and change the production of adipokines like leptin and adiponectin, which are important regulators of body weight, natural products represent a treasure trove for anti-obesity agents. In conclusion, conducting comprehensive research on natural products holds the potential to accelerate the development of an improved obesity management strategy characterized by heightened efficacy and reduced incidence of side effects

Protocol for a randomised feasibility study of Point-Of-care HIV viral load testing to Enhance Re-suppression in South Africa: the POwER study

Introduction Access to HIV viral load testing remains difficult for many people on antiretroviral therapy (ART) in low-income and middle-income countries. Weak laboratory and clinic systems often delay the detection and management of viraemia, which can lead to morbidity, drug resistance and HIV transmission. Point-of-care testing could overcome these challenges. We aim to assess whether it is feasible to conduct a randomised trial of point-of-care viral load testing to manage viraemia.Methods and analysis We will conduct an open-label, single-site, individually randomised, feasibility study of Point-Of-care HIV viral load testing to Enhance Re-suppression, in Durban, South Africa. We will enrol approximately 100 people living with HIV who are aged ≥18 years, receiving first-line ART but with recent viraemia ≥1000 copies/mL, and randomise them 1:1 to receive point-of-care viral load or standard laboratory viral load monitoring, after 12 weeks. All participants will continue to receive care from public sector healthcare workers following South African HIV management guidelines. Participants with persistent viraemia ≥1000 copies/mL will be considered for switching to second-line ART. We will compare the proportion in each study arm who achieve the primary outcome of viral suppression <50 copies/mL at 24 weeks after enrolment. Additional outcomes include proportions retained in the study, proportions with HIV drug resistance, time to viral load results and time to switching to second-line ART. We will assess implementation of point-of-care viral load testing using process evaluation data, and through interviews and focus groups with healthcare workers.Ethics and dissemination University of Oxford Tropical Research Ethics Committee and the Biomedical Research Ethics Committee of the University of KwaZulu-Natal have approved the study. We will present results to stakeholders, and through conferences and open-access, peer-reviewed journals.Trial registration number PACTR202001785886049

Diagnostic accuracy of the rapid Xpert HIV-1 Viral Load XC, Xpert HIV-1 Viral Load & m-PIMA HIV-1/2 Viral Load in South African clinics

Background: We aimed to evaluate the analytic performance of three rapid HIV viral load assays: the novel Xpert HIV-1 VL XC (Xpert XC), the Xpert HIV-1 VL (Xpert VL), and the m-PIMA HIV52 1/2 VL (m-PIMA). Setting: Two South African clinics. Methods: We conducted a prospective diagnostic accuracy study. Site-laboratory technicians and nurses used the Xpert XC, Xpert VL and m-PIMA to test plasma samples from people with HIV receiving antiretroviral therapy. We compared results with the Roche Cobas HIV-1 reference assay. We determined accuracy to detect viraemia at the World Health Organization (WHO) failure threshold of 1000 copies/mL on all three assays, and 50 and 200 copies/mL on the Xpert assays. We assessed agreement using Bland-Altman plots. Results: We enrolled 140 participants (98 [70%] women, median age 37 years), who provided 189 paired samples at one or more timepoints. We tested 174 samples with the Xpert XC, 188 with the Xpert VL, and 128 with the m-PIMA. At 1000 copies/mL, sensitivity and specificity (95% confidence intervals) were 97% (82-100) and 98% (93-99) (Xpert XC), 100% (87-100) and 96% (91-98) (Xpert VL), and 92% (72-99) and 99% (93-100) (m-PIMA) respectively. At 50 copies/mL, sensitivity and specificity were 93% (81-98) and 96% (91-99) (Xpert XC), and 95% (84-99) and 95% (90-98) (Xpert VL) respectively. Mean bias was -0.10 (-0.54 to 0.34) log10 copies/mL (Xpert XC), 0.07 (-0.37 to 0.52) log10 copies/mL (Xpert VL) and -0.26 (-0.83 to 0.31) log10 copies/mL (m-PIMA). Conclusions: In these South African clinics, the accuracy of all three assays was clinically acceptable to detect viraemia at the WHO failure threshold, while both Xpert assays were also accurate at detecting low level viraemia

Natural products as novel anti-obesity agents:insights into mechanisms of action and potential for therapeutic management

Obesity affects more than 10% of the adult population globally. Despite the introduction of diverse medications aimed at combating fat accumulation and obesity, a significant number of these pharmaceutical interventions are linked to substantial occurrences of severe adverse events, occasionally leading to their withdrawal from the market. Natural products serve as attractive sources for anti-obesity agents as many of them can alter the host metabolic processes and maintain glucose homeostasis via metabolic and thermogenic stimulation, appetite regulation, pancreatic lipase and amylase inhibition, insulin sensitivity enhancing, adipogenesis inhibition and adipocyte apoptosis induction. In this review, we shed light on the biological processes that control energy balance and thermogenesis as well as metabolic pathways in white adipose tissue browning, we also highlight the anti-obesity potential of natural products with their mechanism of action. Based on previous findings, the crucial proteins and molecular pathways involved in adipose tissue browning and lipolysis induction are uncoupling protein-1, PR domain containing 16, and peroxisome proliferator-activated receptor-γ in addition to Sirtuin-1 and AMP-activated protein kinase pathway. Given that some phytochemicals can also lower proinflammatory substances like TNF-α, IL-6, and IL-1 secreted from adipose tissue and change the production of adipokines like leptin and adiponectin, which are important regulators of body weight, natural products represent a treasure trove for anti-obesity agents. In conclusion, conducting comprehensive research on natural products holds the potential to accelerate the development of an improved obesity management strategy characterized by heightened efficacy and reduced incidence of side effects.</p