Study of Pathogenicity Test, Antifungal Activity, and Secondary Metabolites of Bacillus spp. from Lake Bogoria as Biocontrol of Rhizoctonia solani Kühn in Phaseolus vulgaris L.

The common bean (Phaseolus vulgaris L.) is a yearly herbaceous plant grown for its edible dry seeds. Despite that, pests and diseases have contributed to the decline of common bean production in Kenya. Therefore, the study aimed to identify bacteria from Lake Bogoria, assess the pathogenicity of Rhizoctonia solani Kühn, screen for effective antifungal agents, and determine secondary metabolites for the biocontrol of R. solani. A total of 49 bacteria were isolated, of which 10 isolates had varied mycelial inhibition rates of R. solani in the co-culture technique. The efficacy of volatile compounds of the three selected bacterial strains had varied mycelial growth and percent reduction against R. solani. The pathogenicity assay showed varied plant parameters and biomass of R. solani on common bean plantlets. The molecular characterization based on 16 S ribosomal RNA confirmed the selected bacterial strains' identity with a diversity similar to the Bacillus genus. Gas chromatography-mass spectrometry analysis of secondary metabolites showed different antimicrobial compounds produced by Bacillus subtilis strain TW21. In conclusion, Lake Bogoria harbors useful microbes as biocontrol agents against plant pathogens. The current study discovers the potential biocontrol bacteria isolates from Lake Bogoria as alternative bioagents against R. solani. Therefore, the isolate Bacillus subtilis strain TW21 can be assessed further for toxicological and ecotoxicological studies and registered by the Pest Control Products Board (PCPB), Kenya, as a biocontrol product against common diseases affecting common beans' production.

Alcohol spiked with zolpidem and midazolam potentiates inflammation, oxidative stress and organ damage in a mouse model.

PURPOSE: Crime-related spiking of alcoholic drinks with prescription drugs is quite common and has been happening for centuries. This study, therefore, evaluated the effects of oral administration of alcohol spiked with the zolpidem and midazolam potent sedatives on inflammation, oxidative stress and various organ damage in male Swiss albino mice. METHODS: Mice were randomly assigned into six treatment groups; the first group constituted the normal control, the second group received 50 mg/kg body weight of zolpidem only, the third group received 50 mg/kg body weight zolpidem dissolved in 5 g/kg alcohol, the fourth group received 50 mg/kg midazolam only, the fifth group received midazolam (50 mg/kg) dissolved in 5 g/kg alcohol and the sixth group received 5 g/kg alcohol. RESULTS: Alcohol-induced significant reduction in neurological function and altered blood hematological indicators. Such neurological impairment and negative effects on blood were exacerbated in mice administered with spiked alcohol. Additionally, midazolam and zolpidem enhanced alcohol-driven elevation of liver function markers; the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) gamma glutamyltransferase (GGT), total bilirubin and alkaline phosphatase. Exposure to alcohol and/or spiked alcohol led to significant augmentation of nitric oxide and malonaldehyde, with concomitant depletion of liver glutathione (GSH) levels. Similarly, serum levels of pro-inflammatory cytokines tumor necrosis factor alpha and interferon-gamma were increased by co-exposure with midazolam or zolpidem. Alcohol-induced hepatotoxicity and nephrotoxicity were amplified by exposure to alcohol spiked with midazolam/zolpidem. CONCLUSION: Exposure to alcohol spiked with midazolam or zolpidem appears to exacerbate neurological deficits, inflammation, oxidative stress, and organ damage.

Sodium Metabisulfite-Induced Hematotoxicity, Oxidative Stress, and Organ Damage Ameliorated by Standardized Ginkgo biloba in Mice.

Sodium metabisulfite (SMB) is a biocide and antioxidant agent generally used as a preservative in food and beverage industries but can oxidize to harmful sulfite radicals. A standardized Ginkgo biloba (EGb-761) has demonstrated potent antioxidant and anti-inflammatory activities, which is beneficial for the treatment of diseases that exhibit oxidative stress and inflammation. The present study sought to investigate the putative ameliorative effects of EGb-761 against SMB-induced toxicity in mice. Thirty-two male Swiss white mice were randomized into control, SMB-treated, SMB + EGb-761-treated, and EGb-761-treated groups. EGb-761 (100 mg/kg/day) and SMB (98 mg/kg/day) were administered by gastric gavage for 40 days. Oral administration of EGb-761 restored SMB-induced decrease in body weight and prevented SMB-induced thrombocytopenia, leukocytosis, and anemia. Furthermore, EGb-761-treatment protected against SMB-induced liver and kidney injury depicted by decreased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, bilirubin, creatinine, urea, uric acid, and albumin. Furthermore, EGb-761 treatment attenuated SMB-driven dyslipidemia and metabolic acidosis. Besides, EGb-761 supplementation abrogated SMB-driven oxidative stress as depicted by stabilized reduced glutathione (GSH) levels in the brain, liver, kidney, spleen, heart, and lungs. SMB induced a significant increase of tissue levels of malondialdehyde (MDA), serum nitric oxide (NO), interferon-gamma (IFN-γ) and tumor necrosis factor-α (TNF-α) which were abrogated by EGb-761 treatment. In conclusion, these results deepen our understanding of EGb-761 in light of various detrimental effects of SMB-driven toxicities. These findings provide a novel approach that can be optimized for preventing or treating exposure due to SMB toxicity.

South-to-south mentoring as a vehicle for implementing sustainable health security in Africa.

BACKGROUND: While sustainability has become a universal precept in the development of global health security systems, supporting policies often lack mechanisms to drive policies into regular practice. 'On-paper' norms and regulations are to a great extent upheld by frontline workers who often lack the opportunity to communicate their first-hand experiences to decisionmakers; their role is an often overlooked, yet crucial, aspect of a sustainable global health security landscape. Initiatives and programs developing transdisciplinary professional skills support the increased bidirectional dialogue between these frontline workers and key policy- and decisionmakers which may sustainably narrow the gap between global health security policy design and implementation. METHODS: The International Federation of Biosafety Associations' (IFBA) Global Mentorship Program recruits biosafety and biosecurity champions across Africa to provide local peer mentorship to developing professionals in their geographic region. Mentors and mentees complete structured one year program cycles, where they are provided with written overviews of monthly discussion topics, and attend optional virtual interactive activities. Feedback from African participants of the 2019-2020 program cycle was collected using a virtual Exit Survey, where aspects of program impact and structure were assessed. RESULTS: Following its initial call for applications, the IFBA Global Mentorship Program received considerable interest from professionals across the African continent, particularly in East and North Africa. The pilot program cycle matched a total of 62 individuals from an array of professional disciplines across several regions, 40 of which were located on the African continent. The resulting mentorship pairs shared knowledge, skills, and experiences towards translating policy objectives to action on the front lines. Mentorship pairs embraced multidisciplinary approaches to harmonize health security strategies across the human and animal health sectors. South-to-South mentorship therefore provided mentees with locally relevant support critical to translation of best technical practices to local capacity and work. CONCLUSION: The IFBA's South-to-South Global Mentorship Program has demonstrated its ability to form crucial links between frontline biosafety professionals, laboratory workers, and policy- and decision-makers across several implicated sectors. By supporting regionally relevant peer mentorship programs, the gap between health security policy development and implementation may be narrowed.

Post-vaccine rotavirus genotype distribution in Nairobi County, Kenya.

BACKGROUND: Rotaviruses are primary etiological agents of gastroenteritis in young children. In Kenya, G1P8 monovalent vaccine (Rotarix) was introduced in July 2014 for mandatory vaccination of all newborns at 6 and 10 weeks of age. Since then, no studies have been done to identify the rotavirus genotypes circulating in Nairobi County, Kenya, following the vaccine introduction, hence the post-vaccine genotype distribution is not known. OBJECTIVES: The aim of this study was to determine the post-vaccine occurrence of rotavirus genotypes in children <5 years of age in Nairobi County, Kenya. METHODS: Stool samples were collected from children presenting with diarrhea for whom the vaccination status was card-confirmed. Fecal samples were analyzed for rotavirus antigen using a commercial enzyme immunoassay (EIA) kit, followed by characterization by polyacrylamide gel electrophoresis, RT-PCR, and nested PCR genotyping, targeting the most medically important genotypes. RESULTS: The strains observed included G1P[8] (38.8%), G9P[8] (20.4%), G2P[4] (12.2%), G3[P4] (6.1%), G2P[6] (4.1%), and G9P[6] (4.1%). Mixed genotype constellations G3P[4][8] were also detected (4.1%). Remarkably, an increased prevalence of G2 genotypes was observed, revealing a change in genetic diversity of rotavirus strains. While the dominance of G1P[8] decreased after vaccination, an upsurge in G2P[4] (12.2%) and G9P[8] (20.4%) was observed. Additionally, G3[P4] (6.1%) and G2P[6] (4.1%) prevalence increased over the 3 years of study. CONCLUSIONS: The results inform the need for robust longitudinal surveillance and epidemiological studies to assess the long-term interaction between rotavirus vaccine and strain ecology.

Coenzyme Q10 nullified khat-induced hepatotoxicity, nephrotoxicity and inflammation in a mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: The consumption of khat (Catha Edulis, Forsk) is on the rise despite the much publicized associated deleterious health effects. How chemicals present in khat, affect various physiological and biochemical processes requires further scrutiny. A clear understanding of these processes will provide an avenue for countering khat-driven negative effects using appropriate pharmacological and/or nutritional interventions. AIM OF THE STUDY: The current study investigated the effect of khat on vital physiological and biochemical processes such as oxidative stress, inflammation and immune responses and the role of Coenzyme-Q10 (CoQ10), a potent antioxidant and anti-inflammatory, in modulating any negative effects due to khat exposure. METHODOLOGY: Three (3) weeks old forty (40) Swiss albino mice were randomly assigned into four treatment groups (n = 10). The first group was the control that was not administered with khat or CoQ10. The second group received 200 mg/kg body weight (b/w) of CoQ10, while the third group received 1500 mg/kg b/w of khat extract and finally the forth group was co-treated with 200 mg/kg b/w of CoQ10 and 1500 mg/kg b/w of khat extract. The experiment was conducted for 90 days after which samples were collected for physiological and biochemical analyses. RESULTS: The effects of khat and CoQ10 on the weights of brain, liver, kidney and spleen was determined. Administration of khat decreased the levels of RBCs and its subtypes (MCV, MCH, RDW-SD and RDW-CV), a clear indicator of khat-induced normochromic microcytic anemia. White blood cells (lymphocytes, monocytes, neutrophils and eosinophil) which are vital in responding to infections were markedly elevated by khat. Moreover, these results provide evidence for khat-induced liver and kidney injury as shown by increased biomarkers; AST, ALT, GGT and creatinine respectively. Standard histopathological analysis confirmed this finding for khat-driven liver and kidney injury. Further studies showed evidence for khat-induced inflammation and oxidative stress as depicted by increased levels of the pro-inflammatory cytokine TNF-alpha and elevation of GSH in the brain, liver and spleen. Remarkably, this is the first study to demonstrate the potential of CoQ10 in ameliorating khat-induced negative effects as outlined. CoQ10 supplementation restored the khat-induced reduction in RBC subtypes, and was protective against liver and kidney injury as shown by the appropriate biomarkers and standard histopathology analysis. The other significant finding was the CoQ10-driven normalization of GSH and TNF-α levels, indicating a protective effect from khat-driven oxidative stress and inflammation respectively. CONCLUSION: From this study, we conclude that CoQ10 may be useful in nullifying khat-driven deleterious events among chronic khat users.

Rotavirus prevalence and seasonal distribution post vaccine introduction in Nairobi county Kenya.

Rotaviruses are one of the leading etiological agents of gastroenteritis in young children, for which a monovalent G1P(8) vaccine has been provided for free in Kenyan since July 2014. The main objective was to estimate the post vaccine prevalence and seasonal distribution of rotavirus diarrhea in children less than 5 years in Nairobi County, Kenya. Rotavirus positive samples were collected from children below 5 years of age in two hospitals within Nairobi County where vaccination status was card-confirmed. The children were examined and the demographic and clinical profiles of the children were recorded. Fecal specimens were analyzed for rotavirus antigen using an ELISA kit, followed by characterization by PAGE. Out of the total 323 samples, 49 had detectable rotavirus infection, representing 15.2% prevalence. Age distribution of rotavirus prevalence was as follows: ≤ 6 months-8.5%, 7-12 months-27.4%, 13-24 months - 41.4%, 25-36 months - 16.4% while 36-65 months had 6.3%. Rotavirus diarrhea was more common in wet and cold months of the year, the highest prevalence being observed in August (24.5%), 12.3% in both July and March, while April scored a prevalence of 10.2%. Out of the 49 rotavirus positive children, 48 had vomiting and abdominal cramps while all had fever and watery stool. The prevalence of Rotaviral diarrhea in children less than 5 years in Nairobi County Kenya has greatly reduced following the vaccine introduction and is more common during the wet and cold seasons of the year.

Lanyamycin, a macrolide antibiotic from Sorangium cellulosum, strain Soce 481 (Myxobacteria).

Lanyamycin (1/2), a secondary metabolite occurring as two epimers, was isolated from the myxobacterium Sorangium cellulosum, strain Soce 481. The structures of both epimers were elucidated from HRESIMS and 1D and 2D NMR data and the relative configuration of their macrolactone ring was assigned based on NOE and vicinal 1H NMR coupling constants and by calculation of a 3D model. Lanyamycin inhibited HCV infection into mammalian liver cells with an IC50 value of 11.8 µM, and exhibited a moderate cytotoxic activity against the mouse fibroblast cell line L929 and the human nasopharyngeal cell line KB3 with IC50 values of 3.1 and 1.5 µM, respectively, and also suppressed the growth of the Gram-positive bacterium Micrococcus luteus.

Hyafurones, hyapyrrolines, and hyapyrones: polyketides from Hyalangium minutum.

Seven new polyketides, for which the trivial names hyafurones A1-B (1-3), hyapyrrolines A (4) and B (5), and hyapyrones A (6) and B (7) are proposed, were isolated from the fermentation broth of the myxobacteria Hyalangium minutum, strains NOCB-2(T) and Hym-3. Their structures were elucidated from NMR and HRESIMS data, and their geometric configuration was assigned based on NOE and vicinal (1)H coupling data. Both hyafurone B (3) and hyapyrone B (7) inhibited growth of the Gram-positive bacterium Nocardia flava, while 7 showed antifungal activity against Mucor hiemalis.

Hyaladione, an S-methyl cyclohexadiene-dione from Hyalangium minutum.

A bioassay-guided fractionation of the crude methanol extract of the myxobacterium Hyalangium minutum, strain NOCB-2(T) (DSM 14724(T)), led to the isolation of hyaladione (1), a novel S-methyl cyclohexadiene-dione. The structure of 1 was established by HRESIMS, NMR, and IR spectroscopy as well as X-ray crystallography. Compound 1 was active against growing mammalian cell lines, with IC(50) values ranging from 1.23 to 3.93 µM, in addition to a broad spectrum of antibacterial and antifungal activities, including inhibition of pathogenic methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa with an MIC of 0.83 and 8.5 µg mL(-1), respectively.

Marinoquinolines A-F, pyrroloquinolines from Ohtaekwangia kribbensis (Bacteroidetes).

Marinoquinoline A (1) was isolated from the gliding bacterium Ohtaekwangia kribbensis together with the novel marinoquinolines B-F (2-6). Their structures were elucidated from NMR and HRESIMS data. The pyrroloquinolines showed weak antibacterial and antifungal activities and moderate cytotoxicity against four growing mammalian cell lines with IC(50) values ranging from 0.3 to 8.0 µg/mL. In a screening against tropical parasites marinoquinolines A-F (1-6) showed activity against Plasmodium falciparum K1 with IC(50) values between 1.7 and 15 µM.