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1.
Int J Mol Sci ; 24(24)2023 Dec 18.
Article in English | MEDLINE | ID: mdl-38139414

ABSTRACT

Lessertia frutescens is a multipurpose medicinal plant indigenous to South Africa that is used for the management of cancer, stomach ulcers, wounds, etc. The use and demand for the raw materials from this plant have been increasing steadily over the years, putting strain on the dwindling wild populations. Although cultivation may provide relief to the strained supply, the persistent drought climate poses a threat to the plant's growth and productivity. This study explored three plant-growth-promoting rhizobacteria isolates, TUTLFNC33, TUTLFNC37 and TUTLFWC74, obtained from the root nodules of Lessertia frutescens as potential bioinoculants that can improve yield, biological activities and the production of secondary metabolites in the host plant. Isolate TUTLFNC37 was identified as the most promising isolate for inoculation of Lessertia frutescens under drought conditions as it induced drought tolerance through enhanced root proliferation, osmolyte proline accumulation and stomatal closure. Superior biomass yield, phenolics, triterpenes and antioxidant activity were evident in the extracts of Lessertia frutescens inoculated with TUTLFNC37 and under different levels of drought. Furthermore, the metabolomics of the plant extracts demonstrated the ability of the isolate to withstand drastic changes in the composition of unique metabolites, sutherlandiosides A-D and sutherlandins A-D. Molecular families which were never reported in the plant (peptides and glycerolipids) were detected and annotated in the molecular networks. Although drought had deleterious effects on Lessertia frutescens, isolate TUTLFNC37 alleviated the impact of the stress. Isolate TUTLFNC37 is therefore the most promising, environmentally friendly alternative to harmful chemicals such as nitrate-based fertilizers. The isolate should be studied to establish its field performance, cross infectivity with other medicinal plants and competition with inherent soil microbes.


Subject(s)
Alphaproteobacteria , Fabaceae , Humans , Drought Resistance , Bioprospecting , Fabaceae/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Plant Development
2.
Sci Rep ; 13(1): 17029, 2023 10 09.
Article in English | MEDLINE | ID: mdl-37813863

ABSTRACT

In most legumes, the rhizobial symbionts exhibit diversity across different environments. Although common bean (Phaseolus vulgaris L.) is one of the important legumes in southern Africa, there is no available information on the genetic diversity and N2-fixing effectiveness of its symbionts in Malkerns, Eswatini. In this study, we assessed the phylogenetic positions of rhizobial microsymbionts of common bean from Malkerns in Eswatini. The isolates obtained showed differences in morpho-physiology and N2-fixing efficiency. A dendrogram constructed from the ERIC-PCR banding patterns, grouped a total of 88 tested isolates into 80 ERIC-PCR types if considered at a 70% similarity cut-off point. Multilocus sequence analysis using 16S rRNA, rpoB, dnaK, gyrB, and glnII and symbiotic (nifH and nodC) gene sequences closely aligned the test isolates to the type strains of Rhizobium muluonense, R. paranaense, R. pusense, R. phaseoli and R. etli. Subjecting the isolates in this study to further description can potentially reveal novel species. Most of the isolates tested were efficient in fixing nitrogen and elicited greater stomatal conductance and photosynthetic rates in the common bean. Relative effectiveness (RE) varied from 18 to 433%, with 75 (85%) out of the 88 tested isolates being more effective than the nitrate fed control plants.


Subject(s)
Phaseolus , Rhizobium , Phaseolus/genetics , Rhizobium/physiology , Phylogeny , Eswatini , Sequence Analysis, DNA , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 16S/analysis , DNA, Bacterial/genetics , Symbiosis/genetics , Root Nodules, Plant/chemistry
3.
Article in English | MEDLINE | ID: mdl-37428357

ABSTRACT

ChatGPT represents an advanced conversational artificial intelligence (AI), providing a powerful tool for generating human-like responses that could change pharmacy prospects. This protocol aims to describe the development, validation, and utilization of a tool to assess the knowledge, attitude, and practice towards ChatGPT (KAP-C) in pharmacy practice and education. The development and validation process of the KAP-C tool will include a comprehensive literature search to identify relevant constructs, content validation by a panel of experts for items relevancy using content validity index (CVI) and face validation by sample participants for items clarity using face validity index (FVI), readability and difficulty index using the Flesch-Kincaid Readability Test, Gunning Fog Index, or Simple Measure of Gobbledygook (SMOG), assessment of reliability using internal consistency (Cronbach's alpha), and exploratory factor analysis (EFA) to determine the underlying factor structures (eigenvalues, scree plot analysis, factor loadings, and varimax). The second phase will utilize the validated KAP-C tool to conduct KAP surveys among pharmacists and pharmacy students in selected low- and middle-income countries (LMICs) (Nigeria, Pakistan, and Yemen). The final data will be analyzed descriptively using frequencies, percentages, mean (standard deviation) or median (interquartile range), and inferential statistics like Chi-square or regression analyses using IBM SPSS version 28. A p<0.05 will be considered statistically significant. ChatGPT holds the potential to revolutionize pharmacy practice and education. This study will highlight the psychometric properties of the KAP-C tool that assesses the knowledge, attitude, and practice towards ChatGPT in pharmacy practice and education. The findings will contribute to the potential ethical integration of ChatGPT into pharmacy practice and education in LMICs, serve as a reference to other economies, and provide valuable evidence for leveraging AI advancements in pharmacy.

4.
Plants (Basel) ; 12(1)2023 Jan 03.
Article in English | MEDLINE | ID: mdl-36616325

ABSTRACT

Lessertia frutescens is a multipurpose medicinal plant indigenous to South Africa. The curative ability of the medicinal plant is attributed to its rich phytochemical composition, including amino acids, triterpenoids, and flavonoids. A literature review of some of the phytochemical compounds, particularly amino acids, in L. frutescens shows a steady decrease in concentration over the years. The reduction of the phytochemical compounds and diminishing biological activities may be attributed to drought and salt stress, which South Africa has been grappling with over the years. Canavanine, a phytochemical which is associated with the anticancer activity of L. frutescens, reduced slightly when the plant was subjected to salt stress. Like other legumes, L. frutescens forms a symbiotic relationship with plant-growth-promoting rhizobacteria, which facilitate plant growth and development. Studies employing commercial plant-growth-promoting rhizobacteria to enhance growth and biological activities in L. frutescens have been successfully carried out. Furthermore, alleviation of drought and salt stress in medicinal plants through inoculation with plant growth-promoting-rhizobacteria is well documented and effective. Therefore, this review seeks to highlight the potential of plant-growth-promoting rhizobacteria to alleviate the effect of salt and drought in Lessertia frutescens.

5.
Toxicon ; 224: 107035, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-36706926

ABSTRACT

The World Health Organization has listed Snakebite Envenoming (SBE) as a priority neglected tropical disease, with a worldwide annual snakebite affecting 5.4 million people and injuring 2.7 million lives. In many parts of rural areas of Africa and Asia, medicinal plants have been used as alternatives to conventional antisnake venom (ASV) due in part to inaccessibility to hospitals. Systemic reviews (SR) of laboratory-based preclinical studies play an essential role in drug discovery. We conducted an SR to evaluate the relationship between interventional medicinal plants and their observed effects on venom-induced experiments. This SR was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The Modified collaborative approach to meta-analysis and review of animal data from experimental studies (CAMARADES) and SYRCLE's risk of bias tools were used to appraise the included studies. Data were searched online in Medline via PubMed, Embase via OVID, and Scopus. Studies reporting in vivo and in vitro pharmacological activities of African medicinal plants/extracts/constituents against venom-induced pathologies were identified and included for screening. Data from the included studies were extracted and synthesized. Ten studies reported statistically significant percentage protection (40-100%) of animals against venom-induced lethality compared with control groups that received no medicinal plant intervention. Sixteen studies reported significant effects (p ≤ 0.05) against venom-induced pathologies compared with the control group; these include hemolytic, histopathologic, necrotic, and anti-enzymatic effects. The plant family Fabaceae has the highest number of studies reporting its efficacy, followed by Annonaceae, Malvaceae, Combretaceae, Sterculiaceae, and Olacaceae. Some African medicinal plants are preclinically effective against venom-induced lethality, hematotoxicity, and cytotoxicity. The evidence was extracted from three in vitro studies, nine in vivo studies, and five studies that combined both in vivo and in vitro models. The effective plants belong to the Fabaceae family, followed by Malvaceae, and Annonaceae.


Subject(s)
Plants, Medicinal , Snake Bites , Animals , Africa , Antivenins/therapeutic use , Asia , Snake Bites/drug therapy , Treatment Outcome
6.
Toxicon X ; 16: 100142, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36438018

ABSTRACT

Snakebite envenoming (SBE) is a common neglected tropical disease in rural communities of Asia, Africa and Latin America. Among the several challenges besetting the control of SBE is inadequate access to high-quality care by snakebite victims, partly contributed by inadequate knowledge of SBE among healthcare professionals (HCPs). This narrative review examined the existing literature on the knowledge of snakebites among HCPs, the factors associated with their knowledge of snakebites and their training needs. Data on the knowledge of healthcare professionals regarding snakebites appeared scanty and were predominantly from studies done in Asia, Africa, and the Middle East. We found that the proportion of health workers with adequate knowledge of local medically important snakes could be as low as 20.2% in some settings in India, while as much as three-quarters of health workers still recommend tourniquets and Blackstone as first aid in some settings in India and Rwanda, respectively. In addition, the mean knowledge score of local snake-induced clinical syndromes could be as low as 46.2% in some settings in Ghana, while 52.7% of tertiary hospital doctors in northern Nigeria recommend antivenom in all snakebite cases. Similarly, 23% of Bhutan health workers have adequate overall knowledge of snakebite management. Furthermore, several sociodemographic characteristics of the HCPs (such as increasing age, years of experience, work setting, medical specialty, health profession and previous involvement in snakebite management) are associated with adequate snakebite knowledge. Moreover, most studies have consistently reported a lack of training on snakebites as a challenge. Therefore, the knowledge gaps identified could be incorporated into training programs and regional policies on SBE treatment protocols.

7.
Toxicol Res ; 38(4): 487-502, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36277361

ABSTRACT

The plant Combretum hypopilinum Diels (Combretaceae) has been utilized in Nigeria and other African nations to treat many diseases including liver, inflammatory, gastrointestinal, respiratory, infectious diseases, epilepsy and many more. Pharmacological investigations have shown that the plant possesses anti-infective, antidiarrhoeal, hepatoprotective, anti-inflammatory, anticancer, sedative, antioxidant, and antiepileptic potentials. However, information on its toxicity profile is unavailable despite the plant's therapeutic potential. As such, this work aimed to determine the acute and sub-acute oral toxic effects of the hydromethanolic leaves extract of C. hypopilinum. The preliminary phytochemical evaluation was carried out based on standard procedures. The acute toxicity evaluation was conducted by oral administration of the extract at the dose of 5000 mg/kg based on the guideline of the Organization of Economic Co-operation and Development (OECD) 423. To investigate the sub-acute toxicity effects, the extract was administered orally to the animals daily for 28-consecutive days at the doses of 250, 500, and 1000 mg/kg. Mortality, body weight and relative organ weight were observed. The hepatic, renal, haematological, and lipid profile parameters were investigated. The liver, kidney, heart, lung, small intestine, and stomach were checked for any histopathological alterations. The results of the phytochemical investigation showed cardiac glycosides, tannins, steroids, flavonoids, alkaloids, saponins, and triterpenes. Based on the acute toxicity investigation outcome, no death and signs of toxic effects were observed. The result showed that the oral median lethal dose (LD50) of the extract was more than the 5000 mg/kg. The extract remarkably reduced the weekly body weight of the animals at 500 mg/kg in the first and second weeks. It also significantly decreased the relative kidney weight, alkaline phosphatase, glucose, potassium, and low-density lipoprotein. There was a remarkable elevation in the percentage of eosinophils, basophils, monocytes, and granulocyte. There were histopathological abnormalities on the kidney, lung, stomach, and small intestine. The extract is relatively safe on acute exposure but moderately toxic at higher doses on sub-acute administration, particularly to the kidney.

8.
Sci Rep ; 12(1): 10629, 2022 06 23.
Article in English | MEDLINE | ID: mdl-35739215

ABSTRACT

This study assessed the genetic diversity and phylogenetic relationships of rhizobial isolates obtained from root nodules of groundnut, jack bean and soybean planted in different locations within Eswatini. Seventy-six rhizobial isolates were studied using ERIC-PCR (enterobacterial repetitive intergenic consensus) fingerprinting and PCR amplification of 16S rRNA, housekeeping genes (atpD, dnaK, glnll and rpoB) and symbiotic genes (nifH and nodC). The dendrogram generated from the ERIC-PCR banding patterns grouped the test rhizobial isolates into 16 major clusters (Cluster I-XVI), with three isolates, namely TUTAHeS60, TUTGMeS3 and TUTAHeS127, forming outgroups of Clusters IV, VI and IX, respectively. Furthermore, the 76 test isolates were grouped into 56 ERIC-PCR types at 70% similarity level. The phylogenetic analysis of the 16S rRNA gene and multilocus sequence analysis of four housekeeping (atpD, dnaK, glnII and rpoB) and two symbiotic (nifH and nodC) genes showed that all three legumes (groundnut, jack bean and soybean) were nodulated by bacterial symbionts belonging to the genus Bradyrhizobium, with some isolates exhibiting high divergence from the known reference type strains. The results also showed that B. arachidis, B. iriomotense and B. canariense were the closest type strains to the groundnut isolates, while B. pachyrhizi and B. elkanii were the closest relatives to the bacterial symbionts associated with the nodulation of both jack bean and soybean. This study is the first report to describe of the bacterial symbionts nodulating jack bean in African soils.


Subject(s)
Bradyrhizobium , Fabaceae , Rhizobium , Arachis/genetics , Canavalia , DNA, Bacterial/genetics , Eswatini , Fabaceae/genetics , Phylogeny , RNA, Ribosomal, 16S/genetics , Rhizobium/genetics , Root Nodules, Plant/microbiology , Sequence Analysis, DNA , Glycine max/genetics , Symbiosis/genetics
9.
Inflammopharmacology ; 30(4): 1143-1151, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35701719

ABSTRACT

The coronavirus disease-2019 (COVID-19) pandemic has become a major global health problem. COVID-19 is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and exhibits pulmonary and extrapulmonary effects, including cardiovascular involvement. There are several attempts to identify drugs that could treat COVID-19. Moreover, many patients infected with COVID-19 have underlying diseases, particularly cardiovascular diseases. These patients are more likely to develop severe illnesses and would require optimized treatment strategies. The current study gathered information from various databases, including relevant studies, reviews, trials, or meta-analyses until April 2022 to identify the impact of SARS-CoV-2 treatment on the cardiovascular system. Studies have shown that the prognosis of patients with underlying cardiovascular disease is worsened by COVID-19, with some COVID-19 medications interfering with the cardiovascular system. The COVID-19 treatment strategy should consider many factors and parameters to avoid medication-induced cardiac injury, mainly in elderly patients. Therefore, this article provides a synthesis of evidence on the impact of different COVID-19 medications on the cardiovascular system and related disease conditions.


Subject(s)
COVID-19 Drug Treatment , Cardiovascular Diseases , Cardiovascular System , Aged , Cardiovascular Diseases/drug therapy , Humans , Pandemics , SARS-CoV-2
10.
Toxicon X ; 14: 100122, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35402895

ABSTRACT

Snakebite envenoming (SBE) is a neglected public health problem, especially in Asia, Latin America and Africa. There is inadequate knowledge of venom toxicokinetics especially from African snakes. To mimic a likely scenario of a snakebite envenoming, we used an enzyme-linked immunosorbent assay (ELISA) approach to study the toxicokinetic parameters in rabbits, following a single intramuscular (IM) administration of Northern Nigeria Naja nigricollis venom. We used a developed and validated non-compartmental approach in the R package PK to determine the toxicokinetic parameters of the venom and subsequently used pharmacometrics modelling to predict the movement of the toxin within biological systems. We found that N. nigricollis venom contained sixteen venom protein families following a mass spectrometric analysis of the whole venom. Most of these proteins belong to the three-finger toxins family (3FTx) and venom phospholipase A2 (PLA2) with molecular weight ranging from 3 to 16 kDa. Other venom protein families were in small proportions with higher molecular weights. The N. nigricollis venom was rapidly absorbed at 0.5 h, increased after 1 h and continued to decrease until the 16th hour (Tmax), where maximum concentration (Cmax) was observed. This was followed by a decrease in concentration at the 32nd hour. The venom of N. nigricollis was found to have high volume of distribution (1250 ± 245 mL) and low clearance (29.0 ± 2.5 mL/h) with an elimination half-life of 29 h. The area under the curve (AUC) showed that the venom remaining in the plasma over 32 h was 0.0392 ± 0.0025 mg h.L-1, and the mean residence time was 43.17 ± 8.04 h. The pharmacometrics simulation suggests that the venom toxins were instantly and rapidly absorbed into the extravascular compartment and slowly moved into the central compartment. Our study demonstrates that Nigerian N. nigricollis venom contains low molecular weight toxins that are well absorbed into the blood and deep tissues. The venom could be detected in rabbit blood 48 h after intramuscular envenoming.

11.
Molecules ; 27(7)2022 Mar 25.
Article in English | MEDLINE | ID: mdl-35408523

ABSTRACT

BACKGROUND: Low-dose aspirin (LDA) is the backbone for secondary prevention of coronary artery disease, although limited by gastric toxicity. This study aimed to identify novel metabolites that could predict LDA-induced gastric toxicity using pharmacometabolomics. METHODS: Pre-dosed urine samples were collected from male Sprague-Dawley rats. The rats were treated with either LDA (10 mg/kg) or 1% methylcellulose (10 mL/kg) per oral for 28 days. The rats' stomachs were examined for gastric toxicity using a stereomicroscope. The urine samples were analyzed using a proton nuclear magnetic resonance spectroscopy. Metabolites were systematically identified by exploring established databases and multivariate analyses to determine the spectral pattern of metabolites related to LDA-induced gastric toxicity. RESULTS: Treatment with LDA resulted in gastric toxicity in 20/32 rats (62.5%). The orthogonal projections to latent structures discriminant analysis (OPLS-DA) model displayed a goodness-of-fit (R2Y) value of 0.947, suggesting near-perfect reproducibility and a goodness-of-prediction (Q2Y) of -0.185 with perfect sensitivity, specificity and accuracy (100%). Furthermore, the area under the receiver operating characteristic (AUROC) displayed was 1. The final OPLS-DA model had an R2Y value of 0.726 and Q2Y of 0.142 with sensitivity (100%), specificity (95.0%) and accuracy (96.9%). Citrate, hippurate, methylamine, trimethylamine N-oxide and alpha-keto-glutarate were identified as the possible metabolites implicated in the LDA-induced gastric toxicity. CONCLUSION: The study identified metabolic signatures that correlated with the development of a low-dose Aspirin-induced gastric toxicity in rats. This pharmacometabolomic approach could further be validated to predict LDA-induced gastric toxicity in patients with coronary artery disease.


Subject(s)
Coronary Artery Disease , Metabolomics , Animals , Aspirin/adverse effects , Humans , Magnetic Resonance Spectroscopy/methods , Male , Metabolomics/methods , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Stomach
12.
Ther Adv Infect Dis ; 9: 20499361211072644, 2022.
Article in English | MEDLINE | ID: mdl-35237433

ABSTRACT

BACKGROUND: Snakebite envenoming (SBE) is a high-priority, neglected, tropical disease that affects millions of people in developing countries annually. The only available standard drug used for the treatment of SBE is antisnake venom (ASV) which consists of immunoglobulins that have been purified from the plasma of animals hyper-immunized against snake venoms. The use of plants as alternatives for treatment of poisonous bites particularly snakebites is important in remote areas where there might be limited, or no access to hospitals and storage facilities for antivenom. The pharmacological activity of some of the medicinal plants used traditionally in the treatment of SBE have also been scientifically validated. METHOD: A systematic review will be conducted according to the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies checklist for study quality in animal/in vivo studies. The tool will be modified and validated to assess in vitro models and studies that combine in vivo and in vitro studies. The systematic review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. English published articles on African medicinal plants used in the treatment of snakebite envenoming will be searched in Medline, Embase, and Scopus from 2000 to 2021. DISSEMINATION: The findings of the study will be communicated through publication in peer-reviewed journal and presentation at scientific conferences. Medicinal plants have been important sources for the development of many effective drugs currently available in orthodox medicine. Botanically derived medicines have played a major role in human societies throughout history. Plants components used in traditional medicine gained much attention by many toxinologists as a tool for designing potent antidotes against snake envenoming. Our systematic review will provide a synthesis of the literature on the efficacy of these medicinal plants. We will also appraise the prospects of African medicinal plants with pharmacologically demonstrated activity against snakebite and envenoming.

13.
J Racial Ethn Health Disparities ; 9(1): 184-192, 2022 Feb.
Article in English | MEDLINE | ID: mdl-33469869

ABSTRACT

BACKGROUND: A relentless flood of information accompanied the novel coronavirus 2019 (COVID-19) pandemic. False news, conspiracy theories, and magical cures were shared with the general public at an alarming rate, which may lead to increased anxiety and stress levels and associated debilitating consequences. OBJECTIVES: To measure the level of COVID-19 information overload (COVIO) and assess the association between COVIO and sociodemographic characteristics among the general public. METHODS: A cross-sectional online survey was conducted between April and May 2020 using a modified Cancer Information Overload scale. The survey was developed and posted on four social media platforms. The data were only collected from those who consented to participate. COVIO score was classified into high vs. low using the asymmetrical distribution as a guide and conducted a binary logistic regression to examine the factors associated with COVIO. RESULTS: A total number of 584 respondents participated in this study. The mean COVIO score of the respondents was 19.4 (± 4.0). Sources and frequency of receiving COVID-19 information were found to be significant predictors of COVIO. Participants who received information via the broadcast media were more likely to have high COVIO than those who received information via the social media (adjusted odds ratio ([aOR],14.599; 95% confidence interval [CI], 1.608-132.559; p = 0.017). Also, participants who received COVID-19 information every minute (aOR, 3.892; 95% CI, 1.124-13.480; p = 0.032) were more likely to have high COVIO than those who received information every week. CONCLUSION: The source of information and the frequency of receiving COVID-19 information were significantly associated with COVIO. The COVID-19 information is often conflicting, leading to confusion and overload of information in the general population. This can have unfavorable effects on the measures taken to control the transmission and management of COVID-19 infection.


Subject(s)
COVID-19 , Social Media , Cross-Sectional Studies , Humans , Pandemics , SARS-CoV-2 , Surveys and Questionnaires
14.
Vaccines (Basel) ; 11(1)2022 Dec 31.
Article in English | MEDLINE | ID: mdl-36679942

ABSTRACT

This study aimed to explore knowledge, attitude, perceptions, and willingness regarding vaccination among university students in Pakistan. This cross-sectional study was carried out using an open online self-administered survey via Google Forms. The survey data were collected between the 15 to 30 of October 2022. A total of 946 respondents participated in the study, of which the majority were female (514, 54.3%). Most students belonged to a medical background, specifically pharmaceutical sciences. Most of the respondents did not know about monkeypox before 2022 (646, 68.3%). Regarding overall knowledge of monkeypox, most of the respondents had average knowledge (726, 76.7%), with very few having good knowledge (60, 6.3%). Regarding overall attitudes towards monkeypox, most of the respondents had neutral attitudes (648, 68.5%). There was a significant association between knowledge of Monkeypox with the type of academic degree (p < 0.001), type of discipline (p < 0.001), and region of respondents (p < 0.001). The willingness to vaccinate among the population was (67.7%). The current study pointed out that the overall knowledge of monkeypox was average in most respondents, with considerable knowledge gaps in most aspects. The overall attitude towards monkeypox was neutral. Further, the knowledge about monkeypox was strongly associated with academic degree, study discipline, and region of respondents. Our findings emphasize the need to raise public awareness by educating students on the monkeypox virus. This will improve adherence to preventative recommendations.

15.
Heliyon ; 7(12): e08482, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34934830

ABSTRACT

ATP synthase subunit c (AtpE) is an enzyme that catalyzes the production of ATP from ADP in the presence of sodium or proton gradient from Mycobacterium tuberculosis (MTB). This enzyme considered an essential target for drug design and shares the same pathway with the target of Isoniazid. Thus, this enzyme would serve as an alternative target of the Isoniazid. The three dimensional (3D) model structure of the AtpE was constructed based on the principle of homology modeling using the Modeller9.16. The developed model was subjected to energy minimization and refinement using molecular dynamic (MD) simulation. The minimized model structure was searched against Zinc and PubChem database to determine ligands that bind to the enzyme with minimum binding energy using RASPD and PyRx tool. A total of 4776 compounds capable of bindings to AtpE with minimum binding energy were selected. These compounds further screened for physicochemical properties (Lipinski rule of five). All the compounds that possessed the desirable property selected and used for molecular docking analysis. Five (5) compounds with minimum binding energies ranged between ─8.69, and ─8.44 kcal/mol, less than the free binding energy of ATP were selected. These compounds further screened for the absorption, distribution, metabolism, excretion, and toxicity (ADME and toxicity) properties. Of the five compounds, three (ZINC14732869, ZINC14742188, and ZINC12205447) fitted all the ADME and toxicity properties and subjected to MD simulation and Molecular Mechanics Generalized Born and Surface Area (MM-GBSA) analyses. The results indicated that the ligands formed relatively stable complexes and had free binding energies, less than the binding energy of the ATP. Therefore, these ligands considered as prospective inhibitors of MTB after successful experimental validation.

16.
Syst Appl Microbiol ; 44(6): 126264, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34601230

ABSTRACT

The study of the nitrogen fixation and phylogenetic diversity of nodule microsymbionts of grain legumes in many parts of the globe is often carried out in order to identify legume-rhizobia combinations for agricultural sustainability. Several reports have therefore found that rhizobial species diversity is shaped by edapho-climatic conditions that characterize different geographic locations, suggesting that rhizobial communities often possess traits that aid their adaptation to their habitat. In this study, the soybean-nodulating rhizobia from semi-arid savannahs of Ghana and South Africa were evaluated. The authenticated rhizobial isolates were highly diverse based on their colony characteristics, as well as their BOX-PCR profiles and gene sequences. In the 16S rRNA phylogeny, the isolates were placed in the different clades Bradyrhizobium iriomotense and Bradyrhizobium jicamae together with two superclades Bradyrhizobium japonicum and Bradyrhizobium elkanii. The multilocus (atpD, glnII, gyrB, recA) phylogenetic analyses indicated the dominance of Bradyrhizobium diazoefficiens and putative new Bradyrhizobium species in the semi-arid Ghanaian region. The phylogenetic analyses based on the symbiotic genes (nifH and nodC) clustered the test isolates into different symbiovars (sv. glycinearum, sv. retame and sv. sojae). Principal component analysis (PCA) showed that soil factors played a significant role in favoring the occurrence of soybean-nodulating microsymbionts in the tested local conditions. The results suggested that isolates had marked local adaptation to the prevailing conditions in semi-arid regions but further studies are needed to confirm new Bradyrhizobium species.


Subject(s)
Fabaceae , Glycine max , Bradyrhizobium , DNA, Bacterial/genetics , Genotype , Ghana , Phylogeny , RNA, Ribosomal, 16S/genetics , Root Nodules, Plant , Sequence Analysis, DNA , South Africa
17.
Ther Adv Infect Dis ; 8: 20499361211039379, 2021.
Article in English | MEDLINE | ID: mdl-34434552

ABSTRACT

INTRODUCTION: Anti-snake venom (ASV) is the standard therapy for the management of snakebite envenoming (SBE). Therefore, the knowledge of ASV among healthcare practitioners (HCPs) is essential for achieving optimal clinical outcomes in snakebite management. This study aimed to assess knowledge of ASV among the HCPs in northern Nigeria. METHODS: We conducted a cross-sectional study involving eligible HCPs from different healthcare settings in northern Nigeria. The participants were recruited into the study using a combination of online (via Google Form) and face-to-face paper-based survey methods. The ASV knowledge of the respondents was measured using a validated anti-snake venom knowledge assessment tool (AKAT). Inadequate overall knowledge of ASV was defined as scores of 0-69.9%, and 70-100% were considered adequate overall knowledge scores. The predictors of ASV knowledge were determined using multiple logistic regression. RESULTS: Three hundred and thirty-one (331) eligible HCPs were included in the study analysis (310 from online and 21 from paper-based survey). Overall, an estimated 12.7% of the participants had adequate knowledge of ASV. Adequate ASV knowledge was higher among physicians compared with other HCPs (21.7%; χ2 = 8.1; p = 0.04). Those without previous training on ASV (adjusted odds ratio [aOR], 0.37; 95% confidence interval [CI], 0.18-0.73; p = 0.004) and who have not previously administered/dispensed ASV (aOR, 0.31; 95% CI, 0.15-0.63; p < 0.001) were less likely to have adequate knowledge of ASV. CONCLUSION: The knowledge of ASV among healthcare practitioners in northern Nigeria is grossly inadequate. Experience with administering or dispensing ASV predicts ASV knowledge. Therefore, appropriate interventions are needed to improve ASV knowledge, particularly among the HCPs, for optimal healthcare outcomes.

18.
Molecules ; 26(14)2021 Jul 19.
Article in English | MEDLINE | ID: mdl-34299638

ABSTRACT

The endoplasmic reticulum (ER) plays a multifunctional role in lipid biosynthesis, calcium storage, protein folding, and processing. Thus, maintaining ER homeostasis is essential for cellular functions. Several pathophysiological conditions and pharmacological agents are known to disrupt ER homeostasis, thereby, causing ER stress. The cells react to ER stress by initiating an adaptive signaling process called the unfolded protein response (UPR). However, the ER initiates death signaling pathways when ER stress persists. ER stress is linked to several diseases, such as cancer, obesity, and diabetes. Thus, its regulation can provide possible therapeutic targets for these. Current evidence suggests that chronic hyperglycemia and hyperlipidemia linked to type II diabetes disrupt ER homeostasis, thereby, resulting in irreversible UPR activation and cell death. Despite progress in understanding the pathophysiology of the UPR and ER stress, to date, the mechanisms of ER stress in relation to type II diabetes remain unclear. This review provides up-to-date information regarding the UPR, ER stress mechanisms, insulin dysfunction, oxidative stress, and the therapeutic potential of targeting specific ER stress pathways.


Subject(s)
Diabetes Mellitus, Type 2/metabolism , Endoplasmic Reticulum Stress , Oxidative Stress , Signal Transduction , Animals , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/pathology , Humans , Hyperglycemia/drug therapy , Hyperglycemia/metabolism , Hyperglycemia/pathology , Hyperlipidemias/drug therapy , Hyperlipidemias/metabolism , Hyperlipidemias/pathology , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/pathology , Obesity/drug therapy , Obesity/metabolism , Obesity/pathology
19.
Sci Rep ; 11(1): 12747, 2021 06 17.
Article in English | MEDLINE | ID: mdl-34140555

ABSTRACT

Identification and symbiotic characterization of indigenous rhizobial isolates are the basis for inoculant formulations needed for sustainable grain legume production. This study screened for morpho-genetic diversity of indigenous cowpea nodulating rhizobia in farmers' fields across two contrasting agroecological zones of Northern Mozambique. The photosynthetic function induced by the isolates in their homologous cowpea was assessed. The results showed high genetic variability among the isolates based on morphology and ERIC-PCR fingerprinting. The trap cowpea genotype did not influence the diversity of isolates collected from the two different agroecologies, suggesting that the cowpea-rhizobia compatibility may be conserved at species level. Phylogenetic analysis of the 16S rRNA gene assigned representative rhizobial isolates to species in the Bradyrhizobium and Rhizobium genera, with some isolates showing high divergence from the known reference type strains. The isolates from both agroecologies highly varied in the number and biomass of nodules induced in the homologous cowpea, resulting in variable plant growth and photosynthetic activities. A total of 72% and 83% of the isolates collected from the agroecological zones 7 and 8 were respectively classified as highly effective candidates with > 80% relative effectiveness compared to plants fertilized with nitrate, indicating that elite native strains populated the studied soils. Moreover, the top 25% of high N2-fixing isolates from the two agroecologies recorded relative effectiveness ranging from 115 to 154%, values higher than the effectiveness induced by the commercial Bradyrhizobium sp. strain CB756. These strains are considered as having potential for use in inoculant formulations. However, future studies should be done to assess the ecologically adaptive traits and symbiotic performance under field conditions.


Subject(s)
Genetic Variation , Rhizobium/genetics , Soil Microbiology , Vigna/microbiology , Ecosystem , Genes, Bacterial , Mozambique , Phylogeny , Plant Roots/microbiology , Polymerase Chain Reaction , RNA, Ribosomal, 16S/genetics , Rhizobium/classification
20.
Data Brief ; 36: 107155, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34041327

ABSTRACT

This article describes the dataset for the elucidation of the possible mechanisms of antidiarrhoeal actions of methanol leaves extract of Combretum hypopilinum (Diels) Combretaceae in mice. The plant has been used in traditional medicine to treat diarrhoea in Nigeria and other African countries. We introduce the data for the antidiarrhoeal activity of the methanol leaf extract of Combretum hypopilinum at 1,000 mg/kg investigated using charcoal meal test in mice with loperamide (5 mg/kg) as the standard antidiarrhoeal agent. To elucidate the possible mechanisms of its antidiarrhoeal action, naloxone (2 mg/kg), prazosin (1 mg/kg), yohimbine (2 mg/kg), propranolol (1 mg/kg), pilocarpine (1 mg/kg) and isosorbide dinitrate (150 mg/kg) were separately administered to different groups of mice 30 minutes before administration of the extract. Each mouse was dissected using dissecting set, and the small intestine was immediately removed from pylorus to caecum, placed lengthwise on moist filter paper and measured the distance travelled by charcoal relative to the length of the intestine using a calibrated ruler in centimetre. Besides, the peristaltic index and inhibition of charcoal movement of each animal were calculated and recorded. The methods for the data collection is similar to the one used to investigate the possible pathways involved in the antidiarrhoeal action of Combretum hypopilinum in mice in the research article by Ahmad et al. (2020) "Mechanisms of Antidiarrhoeal Activity of Methanol Leaf Extract of Combretum hypopilinum Diels (Combretaceae): Involvement of Opioidergic and (α1 and ß)-Adrenergic Pathways" (https://doi.org/10.1016/j.jep.2020.113750) [1]. Therefore, this datasets could form a basis for in-depth research to elucidate further the pharmacological properties of the plant Combretum hypopilinum and its bioactive compounds to develop standardized herbal product and novel compound for management of diarrhoea. It could also be instrumental for evaluating the plant's pharmacological potentials using other computational-based and artificial intelligence approaches, including predictive modelling and simulation.

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