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1.
Appl Clin Genet ; 17: 33-46, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38567200

RESUMO

Tuberculosis remains a global health concern, with substantial mortality rates worldwide. Genetic factors play a significant role in influencing susceptibility to tuberculosis. This review examines the current progress in studying polymorphisms within immune genes associated with tuberculosis susceptibility, focusing on African populations. The roles of various proteins, including Toll-like receptors, Dendritic Cell-Specific Intercellular Adhesion Molecule-3 Grabbing Non-Integrin, vitamin D nuclear receptor, soluble C-type lectins such as surfactant proteins A and D, C-type Lectin Domain Family 4 Member E, and mannose-binding lectin, phagocyte cytokines such as Interleukin-1, Interleukin-6, Interleukin-10, Interleukin-12, and Interleukin-18, and chemokines such as Interleukin-8, monocyte chemoattractant protein 1, Regulated upon activation, normal T-cell expressed and secreted are explored in the context of tuberculosis susceptibility. We also address the potential impact of genetic variants on protein functions, as well as how these findings align with the genetic polymorphisms not associated with tuberculosis. Functional studies in model systems provide insights into the intricate host-pathogen interactions and susceptibility mechanisms. Despite progress, gaps in knowledge remain, highlighting the need for further investigations. This review emphasizes the association of Single Nucleotide Polymorphisms with diverse aspects of tuberculosis pathogenesis, including disease detection and Mycobacterium tuberculosis infection.

2.
Drug Chem Toxicol ; 47(2): 243-251, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38303124

RESUMO

Prolonged use of Highly Active Antiretroviral Therapy (HAART) has been linked to toxicity, particularly hepatotoxicity. There are few effective drugs for HAART patients that promote hepatic cell regeneration and prevent liver injury. Therefore, the purpose of this study was to investigate the hepato-protective activity of Methanol fruit extract of Punica granatum (MFEPG) in HAART-administered rats. Thirty rats weighing between 150-200 g were randomly divided into six groups and each group comprised of five rats. Distilled water was given to the rats in group one. Only HAART was given to the rats in group two. MFEPG at doses of 100 and 400 mg/kg was given to the rats in groups three and four. MFEPG dosages of 100 and 400 mg/kg along with HAART were given to the rats in groups five and six, respectively. All treatments were via oral gavage daily for 40 days. Under halothane anesthesia, all rats were sacrificed on day 41. Liver tissues were utilized for lipid peroxidation marker; Malondialdehyde (MDA), antioxidant enzymes; Superoxide dismutase (SOD) and Catalase (CAT) and histological evaluation, while blood samples were examined for biochemical parameters (AST, ALT, ALP, Total cholesterol, Total protein, and Albumin). The HAART-treated group exhibited a significantly higher amount of the lipid peroxidation end product; MDA, and significantly lower levels of antioxidant enzymes; SOD, and CAT. Liver enzymes and total cholesterol were significantly increased with a significant reduction in Total protein and Albumin levels in the HAART-treated group. Conversely, the liver function biomarkers were returned to normal levels in the HAART and MFEPG-treated groups. Histopathological studies revealed that when HAART-exposed rats were treated with MFEPG, both the biochemical and histological results significantly improved. Thus, the antioxidant activity of MFEPG provides protection against HAART-induced liver oxidative damage. More research is needed to determine the safety of using MFEPG in humans.


Assuntos
Antioxidantes , Punica granatum , Humanos , Ratos , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Ratos Wistar , Punica granatum/metabolismo , Terapia Antirretroviral de Alta Atividade , Metanol , Frutas , Extratos Vegetais/uso terapêutico , Fígado , Superóxido Dismutase/metabolismo , Peroxidação de Lipídeos , Albuminas/metabolismo , Albuminas/farmacologia , Colesterol/metabolismo , Colesterol/farmacologia
3.
J Exp Pharmacol ; 16: 1-11, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38213945

RESUMO

Background: Highly Active Antiretroviral Therapy (HAART) has been linked to oxidative damage to kidney cells leading to renal disease in people living with HIV/AIDS on HAART treatment. The toxic effects of HAART affect the patients' quality of life leading to poor adherence to their regimen. Therefore, the purpose of this study was to investigate the nephron-protective activity of methanol crude peel extract of Punica granatum (MPEPG) in HAART-administered Wistar rats. Methods: Thirty male albino Wistar rats weighing between 180-200g were randomly divided into six groups of five rats each. Group one served as normal control and was given distilled water only. Group two serves as a negative control and was given HAART at a dosage of 64 mg/kg. Groups 3 and 4 were given 100 and 400 mg/kg of MPEPG, respectively, while groups 5 and 6 were given MPEPG dosages of 100 and 400 mg/kg along with HAART, respectively, for 40 days. The rats were sacrificed under halothane anaesthesia, and the kidneys were removed for histological evaluation, while blood samples were analyzed for biochemical parameters. Results: In the HAART (TLD) treated group, there was a significantly high amount of MDA and a lower level of the antioxidant enzymes SOD and CAT. Biochemical analysis revealed that animals treated with HAART (TLD) had significantly higher levels of urea and creatinine, which are biomarkers of kidney damage than the normal control animals. In contrast, all the kidney function markers were returned to normal levels in the HAART-treated group after administration of methanol crude peel extract of P. granatum. The kidney tissues of animals given HAART had considerable structural damage as revealed by histopathological studies. When HAART-exposed rats were treated with MPEPG, both the biochemical and histological results significantly improved. Conclusion: Methanol crude peel extract of P. granatum provided effective protection against kidney oxidative injury brought on by HAART because of its anti-oxidant and free radical scavenging properties.

4.
Heliyon ; 9(3): e13922, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36873543

RESUMO

Information on the basic changes associated with green tea small molecules in acute inflammation is deficient. The purpose of the study was to characterize and establish the effects of green tea silver nanoparticles (AgNPs) following inflammation in BALB/c male mice. In this study, green tea silver nitrate nanoparticles were characterized and the extract were made up to constitute high (100%), medium (10%), and low (1%) concentrations for administration. Acute inflammation was induced in groups I-V of the experimental rodents by injecting 0.5 ml/kg of fresh egg albumin on the subplantar surface of the right hind paw and animals were monitored for 36 h. Group I-III were administered 100%, 10%, 1% green tea nanoparticles extract while group IV was given diclofenac. Group V was the positive control while group VI was the negative control that received the vehicle. Paw edema was measured at a 2 h interval for 3 days, while the pain was assessed by measuring the locomotion activity using the voluntary wheel running and the anxiety-like behavior. Hypersensitivity was measured through the temperature sensation experiment and a non-linear regression analysis was done. Here, synthesized green tea AgNPs registered an absorbance band at 460 nm, phytochemicals due to presence of organic functional groups of O[bond, double bond]C[bond, double bond]O of oxycarbons, of C[bond, double bond]C of a conjugate alkene, C[bond, double bond]O of a stretching bond of a secondary alcohol. The silver green tea nanoparticles were spherical, covered by a slimy layer, capped and stable. Green tea AgNPs significantly decreased temperature hypersensitivity in BALB/c male mice and this demonstrated their protective effects. Low concentrations of green tea nanoparticles inhibited edema thus mimicking effects of diclofenac, however, the percentage of inhibition was highest in medium and high silver-tea nanoparticles concentrations demonstration the importance of concentration in therapeutics. Anxiety was lowest in BALB/c male mice treated with high concentrations of silver green tea nanoparticles, and this led to increased locomotory activity in mice. Green tea AgNPs have strong anti-inflammatory effects at high concentrations. Concentrations of green tea AgNPs modulated basic sensory and motor behaviors in BALB/c male mice demonstrating their importance in complementary and integrative medical practice.

5.
Front Bioeng Biotechnol ; 10: 820218, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35252130

RESUMO

The greatest challenge of the current generation and generations to come is antimicrobial resistance, as different pathogenic bacteria have continuously evolved to become resistant to even the most recently synthesized antibiotics such as carbapenems. Resistance to carbapenems limits the therapeutic options of MDR infections as they are the only safe and effective drugs recommended to treat such infections. This scenario has complicated treatment outcomes, even to the commonest bacterial infections. Repeated attempts to develop other approaches have been made. The most promising novel therapeutic option is the use of nanomaterials as antimicrobial agents. Thus, this study examined the efficacy of Camellia sinensis extract (CSE) and Prunus africana bark extract (PAE) green synthesized Copper oxide nanoparticles (CuONPs) against carbapenem-resistant bacteria. Furthermore, the photocatalytic and antioxidant activities of CuONPs were evaluated to determine the potential of using them in a wide range of applications. CuONPs were biosynthesized by CSE and PAE. UV vis spectroscopy, X-ray Diffraction (XRD), Dynamic light scattering (DLS), Fourier Transform Infrared spectroscopy (FTIR), and Scanning Electron Microscopy (SEM) were used to characterize the nanoparticles. CuONPs susceptibility tests were carried out by the agar well diffusion method. The photocatalytic and antioxidant activities of the CuONPs were determined by the methylene blue and DPPH free radical scavenging assays, respectively. UV vis absorbance spectra registered surface plasmon resonance peaks between 272 and 286 nm, confirming the presence of CuONPs. The XRD array had nine strong peaks at 2θ values typical of CuONPs. FTIR spectra exhibited bands associated with organic functional groups confirming capping and functionalization of the CuONPs by the phytochemicals. DLS analysis registered a net zeta potential of +12.5 mV. SEM analysis revealed that the nanoparticles were spherical and clustered with a mean diameter of 6 nm. Phytosynthesized CuONPs exhibited the highest growth suppression zones of 30 mm with MIC ranging from 30 to 125 µg/ml against MDR bacteria. Furthermore, the CuONPs achieved a methylene blue dye photocatalysis degradation efficiency of 85.5% and a free radical scavenging activity of 28.8%. PAE and CSE successfully bio-reduced copper ions to the nanoscale level with potent antimicrobial, photocatalysis, and antioxidant activities.

6.
Antimicrob Resist Infect Control ; 10(1): 57, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33736698

RESUMO

BACKGROUND: Klebsiella pneumoniae is an opportunistic pathogen that has been implicated as one of commonest cause of hospital and community acquired infections. The K. pneumoniae infections have considerably contributed to morbidity and mortality in patients with protracted ailments. The capacity of K. pneumoniae to cause diseases depends on the presence of an array virulence factors. Coexistence and expression of virulence factors and genetic determinants of antibiotic resistance complicates treatment outcomes. Thus, emergence of pathogenic MDR K. pneumoniae poses a great threat to the healthcare system. However, the carriage of antibiotic resistance among pathogenic K. pneumoniae is yet to be investigated in Uganda. We sought to investigate the carbapenem resistance profiles and pathogenic potential based on capsular serotypes of K. pneumoniae clinical isolates. METHODS: This was a cross sectional study involving use of archived Klebsiella pneumoniae isolates collected between January and December, 2019 at four tertiary hospitals in Uganda. All isolates were subject to antimicrobial susceptibility assays to determine phenotypic antibiotic resistance, pentaplex PCR to detect carbapenemases encoding genes and heptaplex PCR to identify capsular serotypes K1, K2, K3, K5, K20, K54 and K57. RESULTS: The study found an overall phenotypic carbapenem resistance of 23.3% (53/227) and significantly higher genotypic resistance prevalence of 43.1% (98/227). Over all, the most prevalent gene was blaOXA-48-like (36.4%), followed by blaIMP-type (19.4%), blaVIM-type (17.1%), blaKPC-type (14.0%) and blaNDM-type (13.2%). blaVIM-type and blaOXA-48-like conferred phenotypic resistance in all isolates and 38.3% of isolates that harbored them respectively. Capsular multiplex PCR revealed that 46.7% (106/227) isolates were pathogenic and the predominantly prevalent pathotype was K5 (18.5%) followed by K20 (15.1%), K3 (7.1%), K2 (3.1%) and K1 (2.2%). Of the 106 capsular serotypes, 37 expressed phenotypic resistance; thus, 37 of the 53 carbapenem resistant K. pneumoniae were pathogenic. CONCLUSION: The high prevalence of virulent and antibiotic resistant K. pneumoniae among clinical isolates obtained from the four tertiary hospital as revealed by this study pose a great threat to healthcare. Our findings underline the epidemiological and public health risks and implications of this pathogen.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Farmacorresistência Bacteriana , Infecções por Klebsiella/epidemiologia , Proteínas de Bactérias/genética , Estudos Transversais , Humanos , Klebsiella pneumoniae/classificação , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase , Prevalência , Sorogrupo , Centros de Atenção Terciária , Uganda , beta-Lactamases/genética
7.
Sci Rep ; 11(1): 4116, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33602952

RESUMO

Of recent, immense attention has been given to chitosan in the biomedical field due to its valuable biochemical and physiological properties. Traditionally, the chief source of chitosan is chitin from crab and shrimp shells. Chitin is also an important component of fish scales, insects and fungal cell walls. Thus, the aim of this study was to isolate and characterize chitosan from locally available material for potential use in the biomedical field. Chitosan ash and nitrogen contents ranged from 1.55 to 3.5% and 6.6 to 7.0% respectively. Molecular weight varied from 291 to 348KDa. FTIR spectra revealed high degree of similarity between locally isolated chitosan and commercial chitosan with DD ranging from 77.8 to 79.1%. XRD patterns exhibited peaks at 2θ values of 19.5° for both mushroom and banana weevil chitosan while Nile perch scales chitosan registered 3 peaks at 2θ angles of 12.3°, 20.1° and 21.3° comparable to the established commercial chitosan XRD pattern. Locally isolated chitosan exhibited antimicrobial activity at a very high concentration. Ash content, moisture content, DD, FTIR spectra and XRD patterns revealed that chitosan isolated from locally available materials has physiochemical properties comparable to conventional chitosan and therefore it can be used in the biomedical field.


Assuntos
Agaricales/química , Braquiúros/química , Quitosana/química , Musa/química , Percas/metabolismo , Gorgulhos/química , Exoesqueleto/química , Animais , Quitina/química , Peso Molecular , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Uganda , Difração de Raios X/métodos
8.
BMC Res Notes ; 12(1): 425, 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31311592

RESUMO

OBJECTIVE: Passion fruit improvement efforts by conventional breeding have had limited success calling for research into alternative approaches such as tissue culture and genetic engineering. An efficient and reproducible regeneration system is a prerequisite for successful genetic engineering. Currently, there is no reliable regeneration system for Uganda's passion fruit varieties owing to the high heterogeneity of the Passiflora genus. Therefore, this study aimed at establishing an efficient and reproducible regeneration system for Uganda's Passiflora edulis f. flavicarpa (yellow passion fruit) and Passiflora edulis f. edulis (purple passion fruit) for routine utilization with an ultimate goal of improving its agronomic value. RESULTS: The study successfully induced shoots by both direct and indirect organogenesis for the yellow passion fruit variety. Highest shoot induction frequency (14.85%) was achieved on 8.9 µM BAP while 7.9 µM BAP did not initiate any shoots. Optimal shoot elongation and rooting was achieved on 0.44 µM BAP and 5.37 µM α-naphthaleneacetic (NAA) respectively. Rooted yellow passion fruit plantlets were successfully weaned with over 65% survival rates. It took approximately 6 months to produce a weaned healthy passion fruit plant. The purple passion fruit variety proved to be recalcitrant to tissue culture with no successful shoot or callus induction.


Assuntos
Engenharia Genética/métodos , Passiflora/fisiologia , Folhas de Planta/fisiologia , Regeneração/fisiologia , Técnicas de Cultura de Tecidos/métodos , Ácidos Naftalenoacéticos/farmacologia , Organogênese/efeitos dos fármacos , Organogênese/genética , Passiflora/classificação , Passiflora/genética , Folhas de Planta/genética , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Brotos de Planta/genética , Brotos de Planta/crescimento & desenvolvimento , Regeneração/genética , Especificidade da Espécie , Uganda
9.
BMC Res Notes ; 11(1): 629, 2018 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-30170613

RESUMO

OBJECTIVE: In this systematic review, we present the molecular epidemiology and knowledge gaps of the carbapenem resistance in East Africa as well as the future probable research interventions that can be used to address the emergence of carbapenem resistance in the region. RESULTS: The 17 articles which presented concrete information about the prevalence of carbapenem resistance in East Africa were reviewed. Tanzania exhibited the highest level of carbapenem resistance at 35% while DRC had the lowest level at 0.96%. Uganda was the only country with studies documenting CR obtained amongst hospital environment isolates with incidence ranging from 21% in Pseudomonas aeruginosa to 55% in Acinetobacter baumannii. Carbapenem resistance was more exhibited in A. baumannii (23%), followed by P. aeruginosa (17%), Klebsiella pneumoniae (15%), Proteus mirabilis (14%) and Escherichia coli (12%) mainly isolated from respiratory tract, blood, urine and wound/pus. The regional genetic determinants of carbapenem resistance detected were blaIMP, blaVIM-1 blaSPM-l, blaNDM-1, blaOXA-23 blaOXA-24, blaOXA-58 and blaKPC.


Assuntos
Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana , Acinetobacter baumannii , África Oriental , Antibacterianos , Escherichia coli , Humanos , Testes de Sensibilidade Microbiana , beta-Lactamases
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