Animal African Trypanosomiasis (AAT), primarily caused by Trypanosoma congolense, continues to threaten livestock productivity across sub-Saharan Africa. The persistence of the disease is largely driven by antigenic variation of Variant Surface Glycoproteins (VSGs), which enable immune evasion. Lysosomal α-D-mannosidase (LDM) suggestively plays a key role in VSG catabolism, and its inhibition may impair parasite survival. This study employed computational and biochemical approaches to characterize T. congolense lysosomal α-D-mannosidase (TcLDM) and identify potential inhibitory compounds. A high-quality TcLDM homology model was constructed and validated, followed by molecular docking of 38 structural analogues of known α-mannosidase inhibitors retrieved from the ZINC database which led to 4 hits with good selectivity ratio toward the parasite orthologues (ZINC000003795857, ZINC000043929526, ZINC000257502749, ZINC000257502751). Molecular dynamics simulations (100 ns) using GROMACS 2022 confirmed the structural stability of the 4 top ligands, particularly kifunensine (ZINC000003795857) and its analogue ZINC000257502749, which exhibited persistent interactions with key catalytic residues. Experimentally, TcLDM was isolated and partially purified using a combination of ion exchange chromatography and gel filtration to a purification fold of 1.62, revealing a molecular weight of ∼66 kDa, optimal activity at pH 5.0, and KM ≈ 0.503 mM. Kifunensine showed mixed-type inhibition with IC50 = 52.97 μM, significantly reducing catalytic efficiency. In vivo drug incubation infectivity assay showed that kifunensine suppressed parasitemia in a dose-dependent manner, achieving near clearance at higher concentrations. These findings collectively highlight TcLDM as a viable enzyme target and suggest kifunensine and ZINC000257502749 as promising scaffolds for anti-trypanosomal drug design.

Background: Monkeypox has become a significant public health concern owing to the recent epidemics and associated morbidity. The treatment is limited by the availability of drugs, especially in endemic communities. Computational methods can facilitate the discovery and development of new and effective therapies that are affordable. This study was aimed at identifying potential drug candidates from the SuperNatural chemical library against monkeypox virus essential proteins using computational methods. Methods: We identified 7 highly conserved essential proteins involved in monkeypox virus (MPXV) replication, infectivity, and propagation as potential therapeutic targets. A library of 447 orally administrable drug-like compounds from the SuperNatural database was screened against the proteins for potential binders/ligands associations using virtual screening and molecular dynamics simulations. Results: Our search identified hit compounds that mimicked the tecovirimat binding pose and outperformed it in binding affinity. Notably, resveratrol-3-O-D-glucopyranoside showed significant binding affinity to the viral protein F13L, a key protein involved in MPXV transmission. Extensive molecular dynamics simulations showed stable interactions between resveratrol-3-O-β-D-glucopyranoside and F13L, and other hit compounds with their respective targets. Conclusion: Although the predicted interactions require further experimental validation, our results suggested that the identified compounds could be promising therapeutic candidates for the development of novel monkeypox drugs. These findings might underscore the significance of natural compounds in drug discovery and lay the foundation for developing novel antivirals against monkeypox.

Diabetes Mellitus is a chronic metabolic disorder affecting a substantial global population leading to complications such as retinopathy, nephropathy, neuropathy, foot problems, heart attacks, and strokes if left unchecked. Prompt detection and diagnosis are crucial in managing and averting these complications. This study compares the effectiveness of a Decision Tree Classifier and an Artificial Neural Network (ANN) in predicting Diabetes Mellitus. The Decision Tree Classifier demonstrated superior performance, achieving a 97.7% accuracy rate compared to the ANN's 94.7%. The Decision Tree Classifier also achieved higher precision (96.9% vs. 88.8%) and recall (96.5% vs. 90.2%) than the ANN, along with a balanced F1 score of 96.5% versus 90.2%. The Matthews Correlation Coefficient (MCC) confirmed a stronger correlation between predictions and actual labels for the Decision Tree Classifier (87.4%) compared to the ANN (78%). Furthermore, the Area Under Curve (AUC) score of 96% for the Decision Tree Classifier was higher than that of ANN (78%). The relative importance feature analysis clearly established glycated hemoglobin (HbA1c) as the paramount factor in predicting diabetes mellitus. Diabetic patients showed markedly higher cholesterol and triglycerides, increasing cardiovascular risk, while High Density Lipoprotein (HDL) and Low-Density Lipoprotein (LDL) levels showed no significant difference between diabetics and non-diabetics. However, Very Low-Density Lipoprotein (VLDL) was significantly elevated, suggesting altered lipid transport in diabetes. Body Mass Index (BMI) was also notably higher in diabetics, reinforcing the link between obesity and diabetes risk. Principal Component analysis further highlighted five clusters of health-related variables, identifying age-related metabolic indicators (AGE, HbA1c, BMI), kidney function markers (creatinine (Cr), Urea), cardiovascular lipid profiles (Cholesterol, LDL), lipid transport (VLDL), and protective cardiovascular indicator (HDL). The study highlights the superiority of decision tree classifier in predicting Diabetes Mellitus, suggesting its potential for significant clinical applications in diagnosis and management.

Stem Cells (SCs) have become potentially instrumental in addressing many human diseases such as cancer, diabetes, age-related diseases and tissue defects. The unique ability of SCs to multiply indefinitely and differentiate into various cell types makes them invaluable in regenerative medicine and treatment. Regenerative medicine is an advancing field that focuses on restoring tissue and organ function in individuals with severe injuries and chronic illnesses. Pluripotent cells, capable of adopting roles from any of the three germ layers, exhibit exceptional versatility and are promising for a wide range of medical conditions. They also offer a solution to limitations posed by animal models in understanding specific disorders. Recent breakthroughs have shown that combining SCs with cutting-edge technologies like 3D bioprinting and 3D culture systems can revolutionize tissue engineering and organ regeneration. 3D bioprinting allows precise construction of complex tissue structures, bringing us closer to recreating functional organs for transplantation. Moreover, the integration of SCs with gene editing techniques presents unprecedented opportunities for precise genetic modification, correcting disease-causing mutations and opening avenues for personalized therapies. In addition, SCs play an important role in drug discovery and testing, serving as valuable models for studying disease mechanisms and screening potential therapeutic biomolecules. This paper provides a comprehensive exploration of SCs, transcription factors, diverse therapeutic applications of these cells as well as their role in the fields of tissue engineering, 3D bioprinting, 3D culture systems, gene editing, disease modeling, and drug discovery and testing.

Thalassemia represents a diverse group of inherited hematological disorders characterized by defective globin chain synthesis, leading to chronic anemia and associated complications. The complicated pathophysiology of beta-thalassemia involves genetic mutations or rarely deletions of the beta-globin gene on chromosome 11 whereas alpha-thalassemia involves deletions in the HBA1 and HBA2 genes or occasionally alterations to the DNA sequence in or around these genes. These mutation and deletion effects disrupt the balance of α/β-globin chain production, resulting in ineffective erythropoiesis, hemolysis, and a cascade of clinical manifestations including anemia, bone deformities, and iron overload. Advances in diagnostic techniques have enhanced our ability to detect and characterize these mutations, facilitating early and accurate diagnoses. Current management strategies encompass regular blood transfusions, the use of hydroxyurea to improve hemoglobin levels, and iron chelation therapy to prevent iron-related organ damage. Moreover, other therapeutics such as thalidomide for those not responding to hydroxyurea, Sirolimus for patients with immunodeficiencies, and use of vitamin E as an antioxidant have proven to be effective. Innovative therapies such as gene therapy and bone marrow transplantation offer promising curative potential, opening a new era in the treatment of thalassemia. This review focuses on pathophysiological mechanisms underlying thalassemia, explores the diagnostic methodologies, and highlights recent advancements in therapeutic approaches.

Aim: This work aims to contribute toward development of preventive measures for the control of monkeypox (mpox) virus disease through computational design of a multiepitope vaccine. Methods: To accomplish this, we employed a robust immunoinformatics approach to design a putative chimeric vaccine candidate from 18 viral transmembrane proteins. Results: The resulting chimeric vaccine candidate is a 76.4 kDa protein containing 687 amino acids with an estimated isoelectric point of 9.39. In addition, it was predicted to adopt a stable 3D conformation that harbors discontinuous B-cell epitopes and strongly interacts with key immune receptors. Conclusion: The designed hypothetical antigen is a valuable addition to the collection of prospective vaccine candidates for future development and trials against the re-emerging mpox disease.

African trypanosomiasis is caused by Trypanosoma brucei subspecies and available drugs against it, are unsatisfactory due to poor pharmacokinetic properties. Trypanosomal Alternative Oxidase (TAO) is an attractive target for anti-trypanosome rational drug discovery because it is essential for parasite-specific ATP generation and absent in the mammalian host. In this study, 360 filtered ligands from the Universal Natural Product Database were virtually screened and docked on T. brucei brucei TAO (PDB-ID 3VVA). From the virtual screening, 10 ligands with binding energy from -10.6 to -9.0 kcal/mol were selected as hits and further subjected pharmacokinetic and toxicity analyses where all of them passed Lipinski's rule of five. Also, the compounds were non-mutagenic, non-tumorigenic and could cross the blood brain barrier. The two topmost hits (UNPD29179; megacerotonic acid and UNPD41551; a quinazoline derivative) interacted with `four glutamates (Glu123, Glu162, Glu213 and Glu266) close to di-iron (2 iron elements) at the catalytic site of the enzyme. Subsequently, 100 ns MD simulations of the two topmost hits were performed using GROMACS where high RMSD values of 0.75 nm (TAO-UNPD29179) and 0.52 nm (TAO- UNPD41551), low residues fluctuations and consistent values of radius of gyration were observed. Moreover, Solvent Accessible Surface Area showed a consistent value of 160 nm(2) for both complexes while TAO-UNPD29179 had higher number of hydrogen bonds than the TAO-UNPD41551. Similarly, MM/PBSA calculations indicated that UNPD29179 had higher free binding energy with TAO than UNPD41551. The data suggest that megacerotonic acid and a quinazoline derivative could be potential inhibitors of TAO with improved pharmacokinetic properties. Communicated by Ramaswamy H. Sarma

Purpose of Review:The climate change (CC) or global warming (GW) modifies environment that favors vectors' abundance, growth, and reproduction, and consequently, the rate of development of pathogens within the vectors. This review highlights the threats of GW-induced vector-borne diseases (VBDs) in Southern Europe (SE) and the need for mitigation efforts to prevent potential global health catastrophe.Recent Findings:Reports showed astronomical surges in the incidences of CC-induced VBDs in the SE. The recently (2022) reported first cases of African swine fever in Northern Italy and West Nile fever in SE are linked to the CC-modified environmental conditions that support vectors and pathogens' growth and development, and disease transmission.Summary:VBDs endemic to the tropics are increasingly becoming a major health challenge in the SE, a temperate region, due to the favorable environmental conditions caused by CC/GW that support vectors and pathogens' biology in the previously non-endemic temperate regions.

Cats (Felis catus) are important companion animals and potential sources of zoonotic endoparasites. Despite so, investigations into the health status of cats are grossly inadequate in Nigeria, most especially, the feral cats. In this study, a cross-sectional survey was performed with geospatial tools to determine the prevalence of endoparasites in fecal samples of feral cats in Sabon Gari Local Government Area (L.G.A), Kaduna State, Nigeria. A total of 80 cats were involved in trapped, captured, released (TCR) program. Fecal samples obtained from the cats were analyzed using Zinc Sulphate-sucrose solution centrifugal floatation method followed by microscopy. Cat infection was determined by the microscopic detection of ova, cysts, or oocysts. Geographical Information System (GIS) tools were used to determine the spatial distribution of parasitic infections and Kernal Density Algorithm was employed to determine the degree of variations in the prevalence of infections in the study region with respect to possible contamination centers. Overall, the prevalence of endoparasites documented in this study was 85% (68/80). A total of seven helminth parasites and three protozoan parasites were identified. Ancylostoma spp. was the most prevalent helminth with a prevalence of 39% (31/80), while Toxoplasma gondii was the most common protozoan parasite (11%: 9/80) in the study area. Spatial distribution shows that, while some parasites are evenly distributed in the study area, others were clustered in specific locations. Results of the Kernal Density Algorithm analysis shows that people in Hayin Commanda settlement have the highest possibility of getting infection with zoonotic parasites identified in this study. This report highlights the need for development of a comprehensive parasite control strategies in Nigeria with emphasis on One Health approach.

Selective permeability of biological membranes represents a significant barrier to the delivery of therapeutic substances into both microorganisms and mammalian cells, restricting the access of drugs into intracellular pathogens. Cell-penetrating peptides usually 5-30 amino acids with the characteristic ability to penetrate biological membranes have emerged as promising antimicrobial agents for treating infections as well as an effective delivery modality for biological conjugates such as nucleic acids, drugs, vaccines, nanoparticles, and therapeutic antibodies. However, several factors such as antimicrobial resistance and poor drug delivery of the existing medications justify the urgent need for developing a new class of antimicrobials. Herein, we review cell-penetrating peptides (CPPs) used to treat microbial infections. Although these peptides are biologically active for infections, effective transduction into membranes and cargo transport, serum stability, and half-life must be improved for optimum functions and development of next-generation antimicrobial agents. [GRAPHICS] .

Babesia sp. are intracellular parasitic organisms that affects mainly the red blood cells of most mammals, causing the disease known as babesiosis, and transmitted by ticks. Babesisosis is potentially fatal and a major disease of dogs in Nigeria. Therefore, active and routine surveillance is recommended. In this study, the infection was investigated among apparently healthy domestic dogs in six Area Councils of the Federal Capital Territory (FCT), Abuja, Nigeria with the aim of determining the prevalence of the infection and the associated risk factors. Blood samples were collected from dogs (n = 480) at randomly selected households, from September 2015 to August 2016. Data regarding sampling location, sex, age, breed, use, presence or absence of ticks were recorded. Blood smears were prepared, stained with Geimsa stain, and examined under light microscope for Babesia sp. The results showed an overall prevalence of 10.8% Babesia canis infection. The prevalence among dogs examined in the six Area Councils were 6.3%, 12.5%, 10.0%, 12.5%, 11.3%, and 12.5 % for Abaji, AMAC, Bwari, Gwagwalada, Kuje and Kwali Area Council, respectively. The prevalence was highest (12.5%) among dogs from Kwali, AMAC and Gwagwalada, and lowest 5 (6.3%) among dogs from Abaji. Of the infected dogs, 13.7% were females and 8.3%, males. Dogs between 12 < 36 months old had the highest (17.0%) prevalence of infection while those of >60 months of age had the lowest (4.5%). Based on breed, the infection was more prevalent among exotic dogs (12.9%) than cross breeds (9.4%). While none of pet dogs were positive for Babesia canis, prevalence of 11.1% and 11.3% were recorded for guard and hunting dogs, respectively. Tick infestation was recorded for 254 dogs of which 17.3% had Babesia canis while only 3.5% of 226 non-infested dogs were Babesia positive. Babesia infection during the rainy season was 14.6% while 3.5% of dogs were positive during dry season. The data on monthly prevalence showed that August and September had the highest (13.5%) prevalence while January and February had the lowest (2.0%). We conclude that the canine babesiosis in the FCT was significantly dependent on age, use of dogs, tick infestation, and season. Therefore, priorities should be given to these factors while instituting control measures against the infection.

Protozoan parasites of the Order Trypanosomatida infect a wide range of multicellular plants and animals, causing devastating and potentially fatal diseases. Trypanosomes are the most relevant members of the order in sub-Saharan Africa because of mortalities and morbidities caused to humans and livestock. There are growing concerns that trypanosomes are expanding their reservoirs among wild animals, which habours the parasites, withstand the infection, and from which tsetse flies transmit the parasites back to humans and livestock. This study was designed to investigate the potentials of the African hedgehog serving as reservoir for African animal trypanosomes. Five adult hedgehogs alongside five laboratory mice were intraperitoneally inoculated with 106 and 104 of Trypanosoma congolense cells, respectively, and monitored for parasitemia and survival. Serum from twenty hedgehogs was subjected to trypanocidal activity-guided fractionation by successive ion-exchange and gel-filtration chromatographies, followed by characterization with Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis (SDS-PAGE). Hedgehogs were resistant to the infection as no parasite was detected and none died even after 60 days, while all the mice died within 12 days. Both the serum and plasma prepared from hedgehogs demonstrated trypanocidal activity- rapidly killed trypanosomes even when diluted 1000 times. The trypanolytic factor was identified to be proteinaceous with an estimated molecular weight of 115-kDa. For the first time, it is here demonstrated that hedgehog blood has significant trypanolytic activity against T. congolense. The potential application of the hedgehog protein for the breeding of trypanosomosis-resistant livestock in tsetse fly belt is discussed.

Summary Introduction: Nowadays, many synthetic drugs comes with various degrees of side effects, accumulative toxicity and development of resistance by microorganisms. Medicinal plants used worldwide can be developed into modern drugs with little or no side effects and greater efficacy. Objective: The aim of this paper was to document the alternative therapy used in Dutsin-Ma local community in Katsina state, Nigeria. Methods: Ethnobotanical survey was carried out among 40 traditional herbalists. Out of 106 plants found, screening was conducted to include only plants that are prescribed simultaneously by the entire herbalists. Results: We have found 32 species of medicinal plants from 20 families that are used for management and alternative therapy against common ailments such as malaria, diabetes, sickle cell anaemia, hypertension, ulcer, paralysis, typhoid fever and immune deficiency. Conclusion: Traditional medicinal plants provide the alternative therapy for treatment and management of diseases to significant number of people. Herbal practitioners are still relevant to African healthcare system.

Ludwigia abyssinica belongs to the family Onagaraceae, it is native to South America, well distributed in Africa and traditionally used in the treatment of generalized back pain, various skin infections, gastrointestinal and wound disorders. The objective of the study is to establishes some important pharmacognostic profile of L. abyssinica leaves with the hope of assisting in its proper identification as well as standardization for quality and purity. Evaluation of the fresh and powdered sample of the leaves was carried out to determine the micromorphological, chemomicroscopic and some physicochemical parameters of the plant. The microscopy revealed the presence of anomocytic type of stomata in both adaxial and abaxial epidermis with irregular epidermal cells and deeply wavy anticlinal walls on the upper epidermis and with sinous anticlinal walls and polygonal shaped epidermal cells on the lower epidermis. Chemomicroscopic characters present include; cellulose cell wall, lignified cell wall, tannins, starch, calcium oxalate and cutin. The physicochemical parameters evaluated include: moisture content (7.00%), total ash (7.80%), water soluble (4.67%), acid insoluble (2.33%), ethanol extractive value (17.00%), and water extractive value (19.70%). Quantitative leaf microscopy, had shown that on the average stomata number (8.00), stomatal index (12.12%) on upper epidermal layer while on the lower epidermal layer the stomatal number and index were (20.00) and (16.80%) respectively, palisade ratio (13.00), vein islet number (12.00), and vein termination number (11.00). The results of this investigation may be useful for the compilation of a suitable monograph on L.abyssinica.