Diabetes and its associated complications have increasingly become major challenges for global healthcare. The current therapeutic strategies involve insulin replacement therapy for type 1 diabetes (T1D) and small-molecule drugs for type 2 diabetes (T2D). Despite these advances, the complex nature of diabetes necessitates innovative clinical interventions for effective treatment and complication prevention.
View Article and Find Full Text PDFSIRT6 is an emerging regulator of longevity. Overexpression of SIRT6 extends the lifespan of mice. Conversely, SIRT6 knockout mice demonstrate severe metabolic defects and a shortened lifespan.
View Article and Find Full Text PDFHuman sirtuins play important roles in various cellular events including DNA repair, gene silencing, mitochondrial biogenesis, insulin secretion and apoptosis. They regulate a wide array of protein and enzyme targets through their NAD -dependent deacetylase activities. Sirtuins are also thought to mediate the beneficial effects of low-calorie intake to extend longevity in diverse organisms from yeast to mammals.
View Article and Find Full Text PDFThe sirtuin family of NAD-dependent protein deacylases has gained significant attention during the last two decades, owing to their unique enzymatic activities as well as their critical roles in a broad array of cellular events. Innovative chemical probes are heavily pursued for the functional annotation and pharmacological perturbation of this group of "eraser" enzymes. We have developed several series of activity-based chemical probes (ABPs) to interrogate the functional state of active sirtuins in complex biological samples.
View Article and Find Full Text PDFAmong all the NAD precursors, nicotinamide riboside (NR) has gained the most attention as a potent NAD-enhancement agent. This recently discovered vitamin, B3, has demonstrated excellent safety and efficacy profiles and is orally bioavailable in humans. Boosting intracellular NAD concentrations using NR has been shown to provide protective effects against a broad spectrum of pathological conditions, such as neurodegenerative diseases, diabetes, and hearing loss.
View Article and Find Full Text PDFInhibition of nicotinamidase could represent a potential antimalarial since parasites require nicotinic acid to successfully recycle nicotinamide to NAD, and importantly, humans lack this biosynthetic enzyme. Recently, mechanism-based inhibitors of nicotinamidase have been discovered. The most potent compound inhibits both recombinant nicotinamidase and parasites replication in infected human red blood cells (RBCs).
View Article and Find Full Text PDFReports of increasing false-negative HRP2-based rapid diagnostic test results across Africa require constant monitoring of factors associated with these false-negative outcomes, as failure of this diagnostic tool will have severe consequences on malaria treatment and control programs. This study characterized the extent of genetic diversity in the Plasmodium falciparum histidine-rich protein 2 (Pfhrp2) gene in P. falciparum isolates from symptomatic malaria patients across the regions of Ghana.
View Article and Find Full Text PDFAdenosine and its derivatives are important building blocks of the biological system. They serve as the universal energy currency, amplify intracellular signals for various signal transduction pathways, and can also be used as the co-substrates for enzymatic transformations. The synthesis and regulation of adenosine and its analogs rely on the adenosine binding proteins (ABPs).
View Article and Find Full Text PDFBackground: Clinical presentations of malaria in Ghana are primarily caused by infections containing microscopic densities of Plasmodium falciparum, with a minor contribution from Plasmodium malariae and Plasmodium ovale. However, infections containing submicroscopic parasite densities can result in clinical disease. In this study, we used PCR to determine the prevalence of three human malaria parasite species harboured by suspected malaria patients attending healthcare facilities across the country.
View Article and Find Full Text PDFThe human sirtuins are a group of NAD-dependent protein deacylases. They "erase" acyl modifications from lysine residues in various cellular targets including histones, transcription factors, and metabolic enzymes. Through these far-reaching activities, sirtuins regulate a diverse array of biological processes ranging from gene transcription to energy metabolism.
View Article and Find Full Text PDFSubclinical infections that serve as reservoir populations to drive transmission remain a hurdle to malaria control. Data on infection dynamics in a geographical area is required to strategically design and implement malaria interventions. In a longitudinal cohort, we monitored Plasmodium falciparum infection prevalence and persistence, and anti-parasite immunity to gametocyte and asexual antigens for 10 weeks.
View Article and Find Full Text PDFThe mammalian sirtuins are a group of posttranslational modification enzymes that remove acyl modifications from lysine residues in an NAD-dependent manner. Although initially proposed as histone deacetylases (HDACs), they are now known to target other cellular enzymes and proteins as well. Sirtuin-catalyzed simple amide hydrolysis has profound biological consequences including suppression of gene expression, promotion of DNA damage repair, and regulation of glucose and lipid metabolism.
View Article and Find Full Text PDFIntroduction: The global effort to eradicate malaria requires a drastic measure to terminate relapse from hypnozoites as well as transmission via gametocytes in malaria-endemic areas. Primaquine has been recommended for the treatment of P. falciparum gametocytes and P.
View Article and Find Full Text PDFBackground: Monitoring changes in the composition of the species circulating within the population over a period can inform appropriate treatment recommendations. This study monitored variations in the prevalence of four common human species carried by children with asymptomatic malaria infections over a two-year period.
Methods: Two cross-sectional studies were conducted in November 2017 and December 2019.
Background: The Alere™ Malaria Ag P.f Ultra-sensitive RDT (UsmRDT) kit is an HRP2-based malaria rapid diagnostic test (RDT) with enhanced sensitivity relative to the SD Bioline Malaria Ag P.f RDT (mRDT) kit.
View Article and Find Full Text PDFBackground: Parasitological diagnosis generates data to assist malaria-endemic countries determine their status within the malaria elimination continuum and also inform the deployment of proven interventions to yield maximum impact. This study determined prevalence of malaria parasitaemia and mRDT performances among febrile patients in selected health care facilities across Ghana.
Methods: This study was a cross-sectional survey conducted in the previously 10 regions of Ghana from May to August 2018.
Introduction: False-negative malaria rapid diagnostic test (RDT) results amongst symptomatic malaria patients are detrimental as they could lead to ineffective malaria case management. This study determined the nationwide contribution of parasites with Pfhrp2 and Pfhrp 3 gene deletions to false negative malaria RDT results in Ghana.
Methods: This was a cross sectional study where whole blood (~2 ml) was collected from patients presenting with malaria symptoms at 100 health facilities in all the regions in Ghana from May to August 2018.
Background: The ABO and the Rhesus blood group systems, as well as various abnormal haemoglobin (Hb) variants (haemoglobinopathies) are known to influence malaria parasite carriage and disease severity in individuals living in malaria endemic areas. This study identified the blood group and Hb variant distribution and Plasmodium falciparum infection status of afebrile individuals living in southern Ghana.
Methods: Afebrile participants were recruited from Obom (358) in the Greater Accra Region and Ewim (100) and Simiw (329) in the Central Region of Ghana.
Background: are known to respond differently to antimalarial drugs. Herbal products with extended treatment regimens and inadequate dosing information are widely used to treat malaria in Ghana. This study set out to determine the activity of selected herbal extracts on the development of asexual and sexual stage malaria parasites.
View Article and Find Full Text PDFBackground: Red blood cell (RBC) polymorphisms are suggested to influence the course of Plasmodium falciparum malaria. Whereas some variants have been found to be protective, others have been found to enhance parasite development. This study evaluated the effect of variant haemoglobin (Hb) and ABO blood groups on P.
View Article and Find Full Text PDF