Volatile compounds of Bacillus pseudomycoides induce growth and drought tolerance in wheat (Triticum aestivum L.).

The plant growth-boosting biofilm-forming bacteria Bacillus pseudomycoides is able to promote growth and drought stress tolerance in wheat by suppressing the MYB gene, which synthesizes Myb protein (TaMpc1-D4) through secreted volatile compounds. In the present study, Triticum aestivum seeds were inoculated with five distinct bacterial strains. The growth, germination rate, root-shoot length, RWC, and chlorophyll content of seedlings were investigated. Furthermore, the levels of soluble sugars, proteins, H2O2, NO, cell death, and antioxidant enzymes (CAT, SOD, POD, and APX) were observed throughout the growth stage. All of the results showed that B. pseudomycoides had a substantially higher ability to form biofilm and promote these traits than the other strains. In terms of molecular gene expression, B. pseudomycoides inoculation strongly expressed the Dreb1 gene by silencing the expression of MYB gene through secreted volatile compounds. For identifying the specific volatile compound that silenced the MYB gene, molecular docking with Myb protein was performed. Out of 45 volatile compounds found, 2,6-ditert-butylcyclohexa-2,5-diene-1,4-dione and 3,5-ditert-butylphenol had a binding free energy of - 6.2 and - 6.5, Kcal/mol, respectively, which predicted that these compounds could suppress this protein's expression. In molecular dynamics simulations, the RMSD, SASA, Rg, RMSF, and hydrogen bonding values found assured the docked complexes' binding stability. These findings suggest that these targeted compounds may be suppressing Myb protein expression as well as the expression of Dreb1 and other drought response genes in wheat. More research (field trial) into plant growth and drought stress is needed to support the findings of this study.

phytochemdb: a platform for virtual screening and computer-aided drug designing.

The phytochemicals of medicinal plants are regarded as a rich source of diverse chemical spaces that have been used as supplements and alternative medicines in the millennium. Even in this era of combinatorial chemical drugs, phytomedicines account for a large share of the statistics of newly approved drugs. In the field of computational aided and rational drug design, there is an urgent need to develop and build a useful phytochemical database management system with a user-friendly interface that allows proper data storage, retrieval and management. We showed 'phytochemdb', a manually managed database that compiles 525 plants and their corresponding 8093 phytochemicals, aiming to incorporate the activities of phytochemicals from medicinal plants. The database collects molecular formula, three-dimensional/two-dimensional structure, canonical SMILES, molecular weight, no. of heavy atoms, no. of aromatic heavy atoms, fraction Csp3, no. of rotatable bonds, no. of H-bond acceptors, no. of H-bond donors, molar refractivity, topological polar surface area, gastrointestinal absorption, Blood-Brain Barrier (BBB) permeant, P-gp substrate, CYP1A2 inhibitor, CYP2C19 inhibitor, CYP2C9 inhibitor, CYP2D6 inhibitor, CYP3A4 inhibitor, Log Kp, Ghose, Veber, Egan, Muegge, bioavailability scores, pan-assay interference compounds, Brenk, Leadlikeness, synthetic accessibility, iLOGP and Lipinski rule of five with the number of violations for each compound. It provides open contribution functions for the researchers who screen phytochemicals in the laboratory and have released their data. 'phytochemdb' is a comprehensive database that gathers most of the information about medicinal plants in one platform, which is considered to be very beneficial to the work of researchers on medicinal plants. 'phytochemdb' is available for free at https://phytochemdb.com/.

Phytomedicines to Target Hepatitis B Virus DNA Replication: Current Limitations and Future Approaches.

Hepatitis B virus infection (HBV) is one of the most common causes of hepatitis, and may lead to cirrhosis or hepatocellular carcinoma. According to the World Health Organization (WHO), approximately 296 million people worldwide are carriers of the hepatitis B virus. Various nucleos(t)ide analogs, which specifically suppress viral replication, are the main treatment agents for HBV infection. However, the development of drug-resistant HBV strains due to viral genomic mutations in genes encoding the polymerase protein is a major obstacle to HBV treatment. In addition, adverse effects can occur in patients treated with nucleos(t)ide analogs. Thus, alternative anti-HBV drugs of plant origin are being investigated as they exhibit excellent safety profiles and have few or no side effects. In this study, phytomedicines/phytochemicals exerting significant inhibitory effects on HBV by interfering with its replication were reviewed based on different compound groups. In addition, the chemical structures of these compounds were developed. This will facilitate their commercial synthesis and further investigation of the molecular mechanisms underlying their effects. The limitations of compounds previously screened for their anti-HBV effect, as well as future approaches to anti-HBV research, have also been discussed.

Dermal Papilla Cell-Derived Extracellular Vesicles Increase Hair Inductive Gene Expression in Adipose Stem Cells via ß-Catenin Activation.

Recently, extracellular vesicle (EV)-mediated cell differentiation has gained attention in developmental biology due to genetic exchange between donor cells and recipient cells via transfer of mRNA and miRNA. EVs, also known as exosomes, play a role in maintaining paracrine cell communication and can induce cell proliferation and differentiation. However, it remains unclear whether adipose-derived stem cells (ASCs) can adopt dermal papilla (DP)-like properties with dermal papilla cell-derived extracellular vesicles (DPC-EVs). To understand the effect of DPC-EVs on cell differentiation, DPC-EVs were characterized and incubated with ASCs, of monolayer and spheroid cell cultures, in combination with the CAO1/2FP medium specialized for dermal papilla cells (DPCs). DPC-like properties in ASCs were initially evaluated by comparing several genes and proteins with those of DPCs via real-time PCR analysis and immunostaining, respectively. We also evaluated the presence of hair growth-related microRNAs (miRNAs), specifically mir-214-5P, mir-218-5p, and mir-195-5P. Here, we found that miRNA expression patterns varied in DPC-EVs from passage 4 (P4) or P5. In addition, DPC-EVs in combination with CAP1/2FP accelerated ASC proliferation at low concentrations and propagated hair inductive gene expression for versican (vcan), alpha-smooth muscle actin (α-sma), osteopontin (opn), and N-Cam (ncam). Comparison between the expression of hair inductive genes (vcan, α-sma, ctnb, and others), the protein VCAN, α-SMA and ß-Catenin (CTNB), and hair inductive miRNAs (mir-214-5P, mir-218-5p, and mir-195-5p) of DPC-EVs revealed similarities between P4 DPC-EVs-treated ASCs and DPCs. We concluded that early passage DPC-EVs, in combination with CAP1/2FP, enabled ASCs to transdifferentiate into DPC-like cells.

The Influence of Atopic Dermatitis on Health-Related Quality of Life in Bangladesh.

Atopic dermatitis (AD) is the foremost non-fatal skin-related disease that affects all age groups. Despite the growing prevalence of AD in low- and middle-income countries, its physiological consequences remain overlooked in countries like Bangladesh. Therefore, we aim to assess and characterize the influence of AD on the health-related quality of life (HRQoL) in Bangladeshi patients. A cross-sectional study comprising 184 eligible adults (83 men and 101 women; mean age, 33.46 ± 15.44 years) was conducted at the dermatology outpatient department of Shaheed Suhrawardy Medical College Hospital (a tertiary hospital in Dhaka, Bangladesh). AD was determined using the UK Working Party criteria. A structured questionnaire, Eczema Area and Severity Index (EASI), and Dermatology Life Quality Index (DLQI) were administered to obtain information on patient characteristics, AD severity, and HRQoL. The mean DLQI score for the entire sample was 11.29 ± 5.27 (range, 1-26), and 51.60% reported the disease greatly affected their lives. Bivariate analysis revealed significant differences in self-rated health measures of DLQI scores in terms of self-reported AD severity, overall health, and the EASI. In multivariable regression models adjusted for patient characteristics, the self-perceived severe AD group reported significantly higher DLQI scores (coefficient = 2.72; 95% confidence interval (CI) = 0.38-5.05; p = 0.022) than the mild group. Concurrently, we observed a substantial increase in the DLQI scores among patients with moderate and severe EASI scores (coefficient = 1.96, 95% CI = 0.08-3.92, p < 0.05 and coefficient = 4.35, 95% CI = 1.98-6.72, p < 0.001, respectively) than in those with mild EASI scores, suggesting that HRQoL was markedly influenced by greater AD severity. These findings highlight the need for a more patient-centric approach to the management of AD in order to alleviate patient suffering and, thereby, improve HRQoL.

Analysis of the Genetic Diversity Associated With the Drug Resistance and Pathogenicity of Influenza A Virus Isolated in Bangladesh From 2002 to 2019.

The subtype prevalence, drug resistance- and pathogenicity-associated mutations, and the distribution of the influenza A virus (IAV) isolates identified in Bangladesh from 2002 to 2019 were analyzed using bioinformatic tools. A total of 30 IAV subtypes have been identified in humans (4), avian species (29), and environment (5) in Bangladesh. The predominant subtypes in human and avian species are H1N1/H3N2 and H5N1/H9N2, respectively. However, the subtypes H5N1/H9N2 infecting humans and H3N2/H1N1 infecting avian species have also been identified. Among the avian species, the maximum number of subtypes (27) have been identified in ducks. A 3.56% of the isolates showed neuraminidase inhibitor (NAI) resistance with a prevalence of 8.50, 1.33, and 2.67% in avian species, humans, and the environment, respectively, the following mutations were detected: V116A, I117V, D198N, I223R, S247N, H275Y, and N295S. Prevalence of adamantane-resistant IAVs was 100, 50, and 30.54% in humans, the environment, and avian species, respectively, the subtypes H3N2, H1N1, H9N2, and H5N2 were highly prevalent, with the subtype H5N1 showing a comparatively lower prevalence. Important PB2 mutations such D9N, K526R, A588V, A588I, G590S, Q591R, E627K, K702R, and S714R were identified. A wide range of IAV subtypes have been identified in Bangladesh with a diversified genetic variation in the NA, M2, and PB2 proteins providing drug resistance and enhanced pathogenicity. This study provides a detailed analysis of the subtypes, and the host range of the IAV isolates and the genetic variations related to their proteins, which may aid in the prevention, treatment, and control of IAV infections in Bangladesh, and would serve as a basis for future investigations.

Optimal stimulation toward the dermal papilla lineage can be promoted by combined use of osteogenic and adipogenic inducers.

Dermal papilla cells (DPCs) play crucial roles in hair regeneration, but they readily lose their hair-forming ability during in vitro culture. Although the formation of spheroids partially restores the ability, shrinkage of the spheroids makes it difficult to maintain cellular viability. To address this problem, we stimulated DPCs with factors known to induce adipogenic and/or osteogenic differentiation, because DPCs share unique gene expression profiles with adipocytes and osteocytes. We isolated DPCs from versican (vcan)-GFP mice, in which GFP is expressed under the control of a vcan promoter, which is strongly active in DPCs of anagen hair follicles. GFP fluorescence was most intense when the spheroids were made from DPCs cultured in a half-diluted combination of adipogenic and osteogenic media (CAO1/2), a Dulbecco's modified Eagle's medium-based medium that contains 10% FBS, 275 nm dexamethasone, 2.5 mm ß-glycerol phosphate, 12.5 µg·mL-1 ascorbic acid, 0.125 µm isobutylmethylxanthine and 2.5 ng·mL-1 insulin. The dose of each additive used was less than the optimal dose for adipogenic or osteogenic differentiation, and shrinkage of the spheroids was avoided through the addition of fibroblast growth factor 2 and platelet-derived growth factor-AA to  CAO1/2. In addition, the gene and protein expression of vcan, osteopontin, alkaline phosphatase and α-smooth muscle actin in the spheroids were augmented to levels similar to those of the intact dermal papillae, which exhibited restored hair-forming activity. In conclusion, a combination of certain adipogenic and osteogenic inducers, together with fibroblast growth factor 2 and platelet-derived growth factor-AA, can promote differentiation toward the DPC lineage.