Identification of novel and safe fungicidal molecules against fusarium oxysporum from plant essential oils: in vitro and computational approaches.

Phytopathogenic fungi are serious threats in the agriculture sector especially in fruit and vegetable production. The use of plant essential oil as antifungal agents has been in practice from many years. Plant essential oils (PEOs) of Cuminum cyminum, Trachyspermum ammi, Azadirachta indica, Syzygium aromaticum, Moringa oleifera, Mentha spicata, Eucalyptus grandis, Allium sativum, and Citrus sinensis were tested against Fusarium oxysporum. Three phase trials consist of lab testing (MIC and MFC), field testing (seed treatment and foliar spray), and computer-aided fungicide design (CAFD). Two concentrations (25 and 50 μl/ml) have been used to asses MIC while MFC was assessed at four concentrations (25, 50, 75, and 100 μl/ml). C. sinensis showed the largest inhibition zone (47.5 and 46.3 m2) for both concentrations. The lowest disease incidence and disease severity were recorded in treatments with C. sinensis PEO. Citrus sinensis that qualified in laboratory and field trials was selected for CAFD. The chemical compounds of C. sinensis PEO were docked with polyketide synthase beta-ketoacyl synthase domain of F. oxysporum by AutoDock Vina. The best docked complex was formed by nootkatone with -6.0 kcal/mol binding affinity. Pharmacophore of the top seven C. sinensis PEO compounds was used for merged pharmacophore generation. The best pharmacophore model with 0.8492 score was screened against the CMNP database. Top hit compounds from screening were selected and docked with polyketide synthase beta-ketoacyl synthase domain. Four compounds with the highest binding affinity and hydrogen bonding were selected for confirmation of lead molecule by doing MD simulation. The polyketide synthase-CMNPD24498 showed the highest stability throughout 80 ns run of MD simulation. CMNPD24498 (FW054-1) from Verrucosispora was selected as the lead compound against F. oxysporum

Factors associated with financial security, food security and quality of daily lives of residents in Nigeria during the first wave of the COVID-19 pandemic

An online survey was conducted to identify factors associated with financial insecurity, food insecurity and poor quality of daily lives of adults in Nigeria during the first wave of the COVID-19 pandemic. The associations between the outcome (experience of financial loss, changes in food intake and impact of the pandemic on daily lives) and the explanatory (age, sex, education level, anxiety, depression, HIV status) variables were determined using logistic regression analysis. Of the 4439 respondents, 2487 (56.0%) were financially insecure, 907 (20.4%) decreased food intake and 4029 (90.8%) had their daily life negatively impacted. Males (AOR:0.84), people who felt depressed (AOR:0.62) and people living with HIV -PLHIV- (AOR:0.70) had significantly lower odds of financial insecurity. Older respondents (AOR:1.01) had significantly higher odds of financial insecurity. Those depressed (AOR:0.62) and PLHIV (AOR:0.55) had significantly lower odds of reporting decreased food intake. Respondents who felt anxious (AOR:0.07), depressed (AOR: 0.48) and who were PLHIV (AOR:0.68) had significantly lower odds of reporting a negative impact of the pandemic on their daily lives. We concluded the study findings may reflect a complex relationship between financial insecurity, food insecurity, poor quality of life, mental health, and socioeconomic status of adults living in Nigeria during the COVID-19 pandemic

Factors associated with COVID-19 pandemic induced post-traumatic stress symptoms among adults living with and without HIV in Nigeria: a cross-sectional study

Background: Nigeria is a country with high risk for traumatic incidences, now aggravated by the COVID-19 pandemic. This study aimed to identify differences in COVID-19 related post-traumatic stress symptoms (PTSS) among people living and not living with HIV; to assess whether PTSS were associated with COVID-19 pandemic-related anger, loneliness, social isolation, and social support; and to determine the association between PTSS and use of COVID-19 prevention strategies.Methods: The data of the 3761 respondents for this analysis was extracted from a cross-sectional online survey that collected information about mental health and wellness from a convenience sample of adults, 18 years and above, in Nigeria from July to December 2020. Information was collected on the study's dependent variable (PTSS), independent variables (self-reported COVID-19, HIV status, use of COVID-19 prevention strategies, perception of social isolation, access to emotional support, feelings of anger and loneliness), and potential confounder (age, sex at birth, employment status). A binary logistic regression model tested the associations between independent and dependent variables.Results: Nearly half (47.5%) of the respondents had PTSS. People who had symptoms but were not tested (AOR = 2.20), felt socially isolated (AOR = 1.16), angry (AOR = 2.64), or lonely (AOR = 2.19) had significantly greater odds of reporting PTSS (p p Conclusion: The present study identified some multifaceted relationships between post-traumatic stress, HIV status, facemask use, anger, loneliness, social isolation, and access to emotional support during this protracted COVID-19 pandemic. These findings have implications for the future health of those affected, particularly for individuals living in Nigeria. Public health education should be incorporated in programs targeting prevention and prompt diagnosis and treatment for post-traumatic stress disorder at the community level.</p

In-silico prediction of TGF-β1 non-synonymous variants and their impact on binding affinity to Fresolimumab

TGF-β1 is a potent immunoregulatory cytokine that plays diverse roles in development, bone healing, fibrosis, and cancer. However, characterizing TGF-β1 gene variants is challenging because the structural and functional consequences of these variants are still undetermined. In this study, we aimed to perform an in-silico analysis of TGF-β1 non-synonymous variants and their pathogenic effects on the TGF-β1 protein. A total of 10,252 TGF-β1 SNPs were collected from the NCBI dbSNP database and in-silico tools (SIFT, PROVEAN, Mutation Taster, ClinVar, PolyPhen-2, CScape, MutPred, and ConSurf) were used. The in-silico predicted potential variants were further investigated for their binding to the TGF-β1 targeting drug “Fresolimumab”. Molecular docking was performed using HADDOCK and confirmed by PRODIGY and PDBsum. The in-silico analysis predicted four potential TGF-β1 nsSNPs: E47G in the LAP domain of the propeptide and I22T, L28F, and E35D in the mature TGF-β1 peptide. HADDOCK and molecular dynamics simulations revealed that the I22T and E35D variants have higher binding affinity for Fresolimumab as compared to the wild type and L28F variants. Molecular dynamics simulations (100 ns) and principal component analysis showed that TGF-β1 variants influenced the protein structure and caused variations in the internal dynamics of protein complexes with the antibody. Among them, the E35D variant significantly destabilized the TGF-β1 protein structure, resulting in rearrangement in the binding site and affecting the interactions with the Fresolimumab. This study identified four variants that can affect the TGF-β1 protein structure and result in functional consequences such as impaired response to Fresolimumab.: TGF-β1 is a potent immunoregulatory cytokine that plays diverse roles in development, bone healing, fibrosis, and cancer. However, characterizing TGF-β1 gene variants is challenging because the structural and functional consequences of these variants are still undetermined. In this study, we aimed to perform an in-silico analysis of TGF-β1 non-synonymous variants and their pathogenic effects on the TGF-β1 protein. A total of 10,252 TGF-β1 SNPs were collected from the NCBI dbSNP database and in-silico tools (SIFT, PROVEAN, Mutation Taster, ClinVar, PolyPhen-2, CScape, MutPred, and ConSurf) were used. The in-silico predicted potential variants were further investigated for their binding to the TGF-β1 targeting drug "Fresolimumab". Molecular docking was performed using HADDOCK and confirmed by PRODIGY and PDBsum. The in-silico analysis predicted four potential TGF-β1 nsSNPs: E47G in the LAP domain of the propeptide and I22T, L28F, and E35D in the mature TGF-β1 peptide. HADDOCK and molecular dynamics simulations revealed that the I22T and E35D variants have higher binding affinity for Fresolimumab as compared to the wild type and L28F variants. Molecular dynamics simulations (100 ns) and principal component analysis showed that TGF-β1 variants influenced the protein structure and caused variations in the internal dynamics of protein complexes with the antibody. Among them, the E35D variant significantly destabilized the TGF-β1 protein structure, resulting in rearrangement in the binding site and affecting the interactions with the Fresolimumab. This study identified four variants that can affect the TGF-β1 protein structure and result in functional consequences such as impaired response to Fresolimumab.Communicated by Ramaswamy H. Sarma

Computational investigation of Moringa oleifera phytochemicals targeting EGFR: molecular docking, molecular dynamics simulation and density functional theory studies

Epidermal growth factor receptor (EGFR) is a prominent target for anticancer therapy due to its role in activating several cell signaling cascades. Clinically approved EGFR inhibitors are reported to show treatment resistance and toxicity, this study, therefore, investigates Moringa oleifera phytochemicals to find potent and safe anti-EGFR compounds. For that, phytochemicals were screened based on drug-likeness and molecular docking analysis followed by molecular dynamics simulation, density functional theory analysis and ADMET analysis to identify the effective inhibitors of EGFR tyrosine kinase (EGFR-TK) domain. Known EGFR-TK inhibitors (1-4 generations) were used as control. Among 146 phytochemicals, 136 compounds showed drug-likeness, of which Delta 7-Avenasterol was the most potential EGFR-TK inhibitor with a binding energy of -9.2 kcal/mol followed by 24-Methylenecholesterol (-9.1 kcal/mol), Campesterol (-9.0 kcal/mol) and Ellagic acid (-9.0 kcal/mol). In comparison, the highest binding affinity from control drugs was displayed by Rociletinib (-9.0 kcal/mol). The molecular dynamics simulation (100 ns) exhibited the structural stability of native EGFR-TK and protein-inhibitor complexes. Further, MM/PBSA computed the binding free energies of protein complex with Delta 7-Avenasterol, 24-Methylenecholesterol, Campesterol and Ellagic acid as -154.559 ± 18.591 kJ/mol, -139.176 ± 19.236 kJ/mol, -136.212 ± 17.598 kJ/mol and -139.513 ± 23.832 kJ/mol, respectively. Non-polar interactions were the major contributors to these energies. The density functional theory analysis also established the stability of these inhibitor compounds. ADMET analysis depicted acceptable outcomes for all top phytochemicals without displaying any toxicity. In conclusion, this report has identified promising EGFR-TK inhibitors to treat several cancers that can be further investigated through laboratory and clinical tests

Berberine ameliorates the progression of primary sclerosing cholangitis by activating farnesoid X receptor

Primary sclerosing cholangitis (PSC) is a rare cholestatic disease characterized by biliary infiltration, hepatic fibrosis and bile duct destruction. To date, treatment options for PSC are very limited. Therefore, the current study is aimed to investigate the therapeutic potential of berberine (BBR) against PSC. The disease was induced by feeding the mice with 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine (DDC) for four weeks. The serum biochemistry and liver histology were analyzed. Furthermore, the expression of farnesoid X receptor (FXR) was also evaluated by real-time PCR. The results indicated that berberine prevents the progression of PSC by modulating the expression of FXR which ultimately regulates other genes (including Cyp7A1 and BSEP) thus maintaining bile acids homeostasis. Furthermore, the docking analysis showed that berberine interacts with the binding pocket of FXR to activate the protein thus acting as an FXR agonist. In conclusion, data indicate that berberine protects the liver from PSC-related injury. This effect might be due to the modulation of FXR activity

Socio-economic factors associated with post-traumatic stress symptoms among adolescents and young people during the first wave of the COVID-19 pandemic

Abstract This study assessed the association between sociodemographic factors and post-traumatic stress symptoms (PTSS) among 18–24-year-olds during the first wave of the COVID-19 pandemic. This was a secondary analysis of data from 4508 individuals collected through an online survey conducted between June and January 2021. PTSS was measured as a dependent variable using the checklist for post-traumatic stress disorder in civilians. Age, birth sex, sexual, level of education, access to emotional and social support, and emotional distress were the independent variables. A multivariate logistic regression analysis was conducted to determine the associations between the dependent and independent variables while controlling for the country related confounding variables. Females (AOR:2.023), sexual minority individuals (AOR:1.868), those who did not disclose their sexual identify (AOR:1.476), those with poor access to emotional and social support (AOR:4.699) and individuals with no formal education (AOR:13.908), and only primary level education (AOR:4.521) had higher odds of PTSS. The study highlights the multifaceted nature of PTSS during the pandemic and suggests the importance of promoting access of young people, especially females, sexual minority individuals and those with low educational status, to emotional/social support to mitigate the probability of PTSS, especially among sexual minority individuals

A multi-country survey on access to healthcare and treatment services among individuals with critical medical care needs during the first wave of the pandemic

Background Healthcare services were significantly interrupted during the early phase of the COVID-19 pandemic. The aim of the present study was to determine the associations between sociodemographic factors and healthcare access during the first wave of the COVID-19 pandemic among individuals with critical care needs.MethodsThis was a secondary analysis of the data of 5,156 participants recruited from 152 countries during the first wave of the COVID-19 pandemic. The dependent variables were self-reported difficulty of access to health care, challenges with obtaining medication, and the use of alternative medical services. The independent variables were age at last birthday; sex at birth, level of education, employment status and the macro-social vulnerability status. The confounding variable was the country income level. Three multivariable logistic regression analyses were conducted to determine the associations between the dependent variables and the independent variables after adjusting for the confounder.ResultsDifficulty accessing health care services and obtaining medications was experienced by 1922 (37.3%) and 3746 (72.7%) participants respectively. Also, 1433 (27.8%) used alternative medical care. Retirees (AOR:1.59), unemployed (AOR:1.198), people living with HIV (AOR:2.36) and at increased risk of COVID-19 (AOR:2.10), people who used drugs (AOR:1.83) and transacted sex (AOR:1.971) had significantly higher odds for reporting difficulty with access to health care. Males (AOR:1.23), respondents with secondary level of education (AOR:1.39), retirees (AOR:2.19), unemployed (AOR:1.47), people living with HIV (AOR:2.46), people who used drugs (AOR:1.79), transacted sex (AOR:2.71) and those who might be (AOR: 1.66) and were at (AOR: 2.3) increased risk of severe COVID-19 had significantly higher odds for reporting difficulty with access to medications. People who used drugs (AOR:2.093) transacted sex (AOR:1.639), who might be (AOR: 1.211) and were at (AOR: 1.511) increased risk of severe COVID-19, and who had difficulty accessing usual healthcare (AOR: 9.047) and obtaining medications (AOR:2.16) had significantly higher odds of reporting alternative medical care use. People living with HIV (AOR:0.562) had significantly lower odds of using alternative medical care.ConclusionWe identified populations who had challenges with access to healthcare and obtaining medications used alternative medical care except for people living with HIV. Priority attention should be given to alternative medical care use during future health pandemics.Peer reviewe