Multiple Isomers of Photolumazine V Bind MR1 and Differentially Activate MAIT Cells.

In response to microbial infection, the nonclassical Ag-presenting molecule MHC class I-related protein 1 (MR1) presents secondary microbial metabolites to mucosal-associated invariant T (MAIT) cells. In this study, we further characterize the repertoire of ligands captured by MR1 produced in Hi5 (Trichoplusia ni) cells from Mycobacterium smegmatis via mass spectrometry. We describe the (to our knowledge) novel MR1 ligand photolumazine (PL)V, a hydroxyindolyl-ribityllumazine with four isomers differing in the positioning of a hydroxyl group. We show that all four isomers are produced by M. smegmatis in culture and that at least three can induce MR1 surface translocation. Furthermore, human MAIT cell clones expressing distinct TCR ß-chains differentially responded to the PLV isomers, demonstrating that the subtle positioning of a single hydroxyl group modulates TCR recognition. This study emphasizes structural microheterogeneity within the MR1 Ag repertoire and the remarkable selectivity of MAIT cell TCRs.

Prevalence of inappropriate antibiotic doses among pediatric patients of inpatient, outpatient, and emergency care units in Bangladesh: A cross-sectional study.

The heterogeneous pediatric populations, their physiological differences, along with the necessity of performing additional dose calculation, make the pediatric population more vulnerable to the incidences of inappropriate antibiotic doses. This study was conducted to examine and evaluate the appropriateness of antibiotic doses. A cross-sectional study with a quantitative approach was conducted in three hospitals located in Savar from January 06, 2021 to October 17, 2022. This study had used a convenient sampling method to collect 405 filled prescription orders from heterogeneous pediatric patients prescribed by physicians from emergency, inpatient, and outpatient care units of various clinical settings. The Harriet Lane Handbook was used as reference to investigate inappropriate doses of antibiotics. Subsequently, all analyses were conducted using the RStudio 1.3.959 software. Binary logistic regression was used to assess the risk of inappropriate antibiotic prescription in pediatrics. The overall prevalence of inappropriate antibiotic dosing in pediatrics was 335 out of 545 (61.5%). Overdosing (36.3%) and oral antibiotic prescriptions (64%) were more common than underdosing (20.4%) and parenteral antibiotics (36%). The majority (230 out of 405, 56.8%) of pediatric patients had prescriptions with inappropriate antibiotic doses, with prevalence rates of 33.8% for inpatients, 86.7% for outpatients, and 50% for emergency pediatrics. The results also indicated that pediatric patients in outdoor and emergency care units, infants, toddlers, and early childhood, those prescribed two antibiotics simultaneously, and those receiving parenteral antibiotics, were less likely to have inappropriate antibiotic dosages in their prescriptions. This study demonstrated that about one out of every two prescriptions had inappropriate antibiotic doses; in particular, prescriptions containing only one antibiotic exhibited a substantial proportion of inappropriate antibiotic doses. Inappropriate antibiotic doses may result in therapeutic failure, patient harm, and antibiotic resistance. Good clinical pharmacy practice and careful adherence to pediatric dosing standards may minimize inappropriate antibiotic doses.

Knowledge, attitudes, and practices regarding antibiotic use in Bangladesh: Findings from a cross-sectional study.

BACKGROUND: Escalating antibiotic resistance presents a notable worldwide dilemma, pointing a large involvement of general population. The objective of this study was to assess knowledge, attitudes, and practices regarding the utilization of antibiotics among Bangladeshi residents. METHODS: A cross-sectional study, conducted from January 01 to April 25, 2022, included 1,947 Bangladeshi adults with a history of antibiotic use, via online surveys and face-to-face interviews using a pretested semi-structured questionnaire. Descriptive statistics, Chi-square tests, and multivariate linear regression models were employed. RESULTS: Mean scores for knowledge, attitudes, and practices were 6.59±1.20, 8.34±1.19, and 12.74±2.59, with correct rates of 73.22%, 92.67%, and 57.91%. Positive predictors for knowledge included being unmarried (ß = 0.10, p = 0.001), higher education (College: ß = 0.09, p = 0.025; Bachelor: ß = 0.22, p<0.001; Master or above: ß = 0.14, p<0.001), various professions (student: ß = 0.57, p<0.001; housewife: ß = 0.33, p<0.001; employee: ß = 0.53, p<0.001; businessman: ß = 0.31, p<0.001; unemployed: ß = 0.15, p<0.001), and residing in semi-urban (ß = 0.32, p<0.001) or urban areas (ß = 0.15, p<0.001). Positive predictors for attitudes included being married (ß = 0.18, p<0.001), specific professions (student: ß = 1.06, p<0.001; housewife: ß = 0.33, p<0.001; employee: ß = 0.86, p<0.001; businessman: ß = 0.37, p<0.001; unemployed: ß = 0.47, p<0.001), higher SES (Lower-middle: ß = 0.22, p<0.001; Middle: ß = 0.26, p<0.001), and residing in semi-urban areas (ß = 0.18, p<0.001); negative predictors included higher education (College: ß = -0.12, p = 0.001; Master or above: ß = -0.09, p = 0.008) and being rich (ß = -0.13, p<0.001). Positive predictors for practices included being married (ß = 0.18, p<0.001), specific professions (student: ß = 0.32, p<0.001; employee: ß = 0.43, p<0.001; businessman: ß = 10, p = 0.034; unemployed: ß = 0.11, p = 0.009), and higher SES (Lower-middle: ß = 0.14, p = 0.009; Middle: ß = 0.38, p<0.001; Higher-middle: ß = 0.15, p = 0.008); negative predictors included higher education (College: ß = -0.21, p<0.001), being rich (ß = -0.12, p<0.001), residing in semi-urban (ß = -0.14, p<0.001) or urban areas (ß = -0.16, p<0.001). CONCLUSIONS: Participants exhibited adequate knowledge and positive attitudes but lagged behind in proper practice of antibiotic use. Proper initiatives should be tailored to enhance prudent antibiotic use and mitigate the risk of antimicrobial resistance.

Delivery of loaded MR1 monomer results in efficient ligand exchange to host MR1 and subsequent MR1T cell activation.

MR1-restricted T cells have been implicated in microbial infections, sterile inflammation, wound healing and cancer. Similar to other antigen presentation molecules, evidence supports multiple, complementary MR1 antigen presentation pathways. To investigate ligand exchange pathways for MR1, we used MR1 monomers and tetramers loaded with 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU) to deliver the antigen. Using MR1-deficient cells reconstituted with wild-type MR1 or MR1 molecules that cannot bind 5-OP-RU, we show that presentation of monomer-delivered 5-OP-RU is dependent on cellular MR1 and requires the transfer of ligand from the soluble molecule onto MR1 expressed by the antigen presenting cell. This mode of antigen delivery strengthens the evidence for post-ER ligand exchange pathways for MR1, which could represent an important avenue by which MR1 acquires antigens derived from endocytosed pathogens.

Positive impacts of COVID-19 Lock down in Bangladesh: An online investigation.

Background: This research focuses on the positive impacts of the COVID-19 lockdown on society and the environment, despite acknowledging the widespread negative effects of the pandemic and lockdown measures. The research was aimed at pinpointing and evaluating the beneficial results stemming from these measures. Method: Data for the study was collected through an online survey distributed via Google forms to adults over the age of 18 across the country. A total of 1230 participants completed the survey, mostly from rural areas (61.7%), providing valuable insights for analysis. The questionnaire encompassed personal, family, and cohesive social data, along with information on the environment and biodiversity. The study utilized structural equation modeling (SEM) and confirmatory factor analysis (CFA) to analyze the data and examine correlations between variables. Results: The findings indicated that the COVID-19 lockdown had positive implications for individuals and society, leading to increased health consciousness, improved family relationships, and constructive social attitudes. Moreover, restrictions on access to natural tourist destinations and parks during the lockdown contributed to positive changes in biodiversity. These results highlight the importance of adopting appropriate measures during pandemics to foster personal and social well-being, as well as the preservation of natural environments and biodiversity. Conclusion: This study emphasizes the need for further research to promote sustainable living in similar situations. By understanding the data appropriately, individuals can play a constructive role in future pandemics, leading to positive outcomes for both society and the environment.

Therapeutic Potentials of Colocasia affinis Leaf Extract for the Alleviation of Streptozotocin-Induced Diabetes and Diabetic Complications: In vivo and in silico-Based Studies.

INTRODUCTION: Hypoglycemia in diabetes mellitus (DM) correlates with hepatic impairment, nephropathy, lipid abnormalities, and oxidative stress and subsequently complicates the disease pathogenesis. Medicinal plants have been used for the management of diabetes since ancient times. In this study, we explored the potentials of Colocasia affinis (CA), a plant known to possess anti-allergic and anti-inflammatory activities, as a remedy for diabetes and related complications. METHODS: We induced diabetes in rats using a single intraperitoneal dose (65 mg/kg) of streptozotocin (STZ). We next treated the rats with an ethanolic extract of leaves of CA to reveal its antidiabetic and organ-protective potentials. Biomarkers of diabetes, inflammation, and oxidative stress were measured using biochemical and histopathological analysis. We also performed molecular docking for three major phytochemicals (kaempferol, myricetin, and rosmarinic acid) of CA. RESULTS: Oral administration of the CA leaves extract at 250 mg/kg and 500 mg/kg doses decreased blood glucose level significantly (p<0.05) in STZ-induced diabetic rats. The extract also considerably attenuated plasma HbA1c levels and normalized blood lipids, glycogen, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Additionally, treatment with the extract improved kidney complications by decreasing serum creatinine and blood urea nitrogen (BUN) levels. Furthermore, CA leaves extract normalized nitric oxide (NO) and advance oxidative protein products (AOPP) in diabetic rats. The extract also showed significant improvement of the antioxidant enzymes glutathione dismutase (GSH) and superoxide dismutase (SOD) at a dose of 500 mg/kg. Besides, histological investigation demonstrated attenuation of inflammation of the vital organs, including the liver and the kidney. In silico studies revealed that three major phytochemicals (kaempferol, myricetin, and rosmarinic acid) of the ethanolic extract of leaves of CA can inhibit several molecular targets of diabetes and inflammation. CONCLUSION: Collectively, our results demonstrated the therapeutic potentials of CA for the mitigation of diabetes and diabetic complications.

Polyhydroxybutyrate and its copolymer with polyhydroxyvalerate as biomaterials: influence on progression of stem cell cycle.

Poly(3-hydroxybutyrate) (PHB) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) are biopolyesters reported to provide favorable microenvironments for cell culture and possess potential for tissue engineering applications. Both biopolymers have been investigated for applications in a variety of medical scenarios, including nerve and bone repair. This study investigated the influence these biomaterials exerted on cell cycle progression of olfactory ensheathing cells (OECs) and mesenchymal stem cells (MSCs) commonly used in the engineering of nerve and bone tissues. Cell cycle regulation is important for cell survival; analysis revealed that the biomaterials induced significant cell cycle progression in both MSCs and OECs. Significantly higher percentages of cells were cycled at synthesis (S) phase of the cycle on PHBV films compared to PHB, with MSCs more susceptible than OECs. Furthermore, detection of early stages of apoptotic activation showed significant differences in the two cell populations exhibiting necrosis and apoptosis when cultivated on the biomaterials. OECs compromised on PHB (5.6%) and PHBV (2.5%) compared to MSCs with 12.6% on PHB and 17% on PHBV. Significant differences in crystallinity and surface rugosity were determined between films of the two biomaterials, 88% and 1.12 µm for PHB and 76% and 0.72 µm for PHBV. While changes in surface properties may have influenced cell adhesion, the work presented here suggests that application of these biomaterials in tissue engineering are specific to cell type and requires a detailed investigation at the cell-material interface.

Ameliorative effects of ethanolic constituents of Bangladeshi propolis against tetracycline-induced hepatic and renal toxicity in rats.

The study reports the phenolic composition of propolis from Bangladesh and its ameliorative effects against tetracycline-induced hepatonephrotoxicity in rats. Male Wistar Albino rats (n = 18) were randomly divided into three following groups: (1) normal control, (2) tetracycline-treatment (200 mg kg-1  rat-1 ), and (3) tetracycline (200 mg kg-1  rat-1 ) + propolis (100 mg kg-1  rat-1 ) treatments. The ethanolic extract of propolis contained major phenolic acids as well as a flavonoid, rutin. Oral exposure to tetracycline caused severe hepatic and renal damage as indicated by significant alterations in liver marker enzymes in rat serum: bilirubin and protein concentrations, lipid profile, and markers of kidney function when compared with controls. The observed biochemical perturbations were accompanied by histopathological changes. Co-administration with propolis extract, however, prevented the changes in biochemical parameters, as revealed by maintenance of cell membrane integrity and regulation of lipid profile and the conservation of the histoarchitecture. PRACTICAL APPLICATIONS: Propolis is a resinous honeybee product which is becoming increasingly popular due to its potential contributions to human health. The phenolic compounds identified in propolis from Bangladesh were effective against tetracycline-induced hepatic and renal toxicity. Propolis may be a promising natural product in reducing the effects of chronic liver and kidney damage.

Constraints on coastal dune invasion for a notorious plant invader.

Although most biological invasions are not successful, relatively few studies have examined otherwise notorious invaders in systems where they are not highly problematic. The annual grass Bromus tectorum is a dominant invader in western North America, but is usually confined to human-dominated and disturbed systems (e.g. roadsides and parking lots) in the East where it remains virtually unstudied. This study aims to address fundamental ecological questions regarding B. tectorum in a Cape Cod dune ecosystem. (i) What is the range of variation in population dynamics and the potential for population growth? (ii) Which factors influence its local abundance and distribution? We observed substantial variation in population dynamics over 3 years, with the number of adult B. tectorum individuals increasing substantially between the first 2 years (λ = 9.24) and then decreasing (λ = 0.43). Population growth in terms of total seeds was similarly variable, but to a lesser extent (λ = 2.32 followed by λ = 0.32). Experimental soil disturbance led to a more than 10-fold increase in mean seedling emergence, and high sensitivity to differences in emergence carried this effect through the life cycle. In contrast, barriers to seed dispersal had no effect on population dynamics, suggesting limited dispersal in this system. Across the landscape, the presence of B. tectorum was associated with areas of higher plant diversity as opposed to those with a strong dominant (e.g. the foredune, dominated by Ammophila breviligulata, or low heathlands, characterized by Hudsonia tomentosa and Arctostaphylos uva-ursi). Overall, we find that B. tectorum is capable of both substantial population growth and decline in a dune ecosystem, but is likely limited without disturbance and dispersal agents. Thus, management actions that restrict dune access (e.g. for nesting habitat) likely have the co-benefit of limiting the invasive potential of B. tectorum.

A comprehensive protein expression profile of extracellular matrix biomaterial derived from porcine urinary bladder.

AIMS: To generate a comprehensive profile of the protein composition of xenogeneic biomaterial, derived from porcine urinary bladder matrix (UBM). MATERIALS & METHODS: Tunica layers and muscularis mucosa were removed from bladders using mechanical delamination. UBM was prepared using a solution of peracetic acid in ethanol, lyophilized then milled into powder. UBM biomaterial was subjected to tryptic digests and components separated using high-performance liquid chromatography with an ion trap mass spectrometer and identified through databases. RESULTS: A repertoire of 129 proteins with neurotrophic, antiangiogenic and tumor-suppressive activities and those associated with tissue remodeling and wound repair were identified. CONCLUSION: This study provides the first insight into the complex nature of the UBM and how its application may be tailored for specific applications in regenerative medicine. We propose that the UBM be further investigated for reconstructive and regenerative remodeling of cardiac and dermal tissues, as well as peripheral nerves.

Coalescence of extracellular matrix (ECM) from porcine urinary bladder (UBM) with a laser-activated chitosan-based surgical adhesive.

Urinary bladder matrix (UBM) has been extensively investigated as a naturally occurring biomaterial in therapeutic applications for tissue repair or regeneration, while other strategies involve biopolymers such as chitosan for tissue reconstruction. The coalescence of UBM with chitosan has considerable potential in enhancing tissue reconstruction. Characterisation of a novel, laser-activated, chitosan-based, thin-film surgical adhesive with UBM in various morphologies showed that the films had increased surface rugosities and crystallinities (Ra approx. 0.83 um, approx. 12% crystallinity) when compared to the chitosan adhesive alone (R a = 0.74 um, 7% crystallinity). Tensile strength of the films was significantly increased by the addition of UBM in particulate form (12.1-32.4 MPa). Furthermore, tissue adhesion strengths using these hybrid biomaterials were maintained at approx. 15 kPa compared to 3 kPa for fibrin glue. Histological analysis demonstrated that laser irradiation of the UBM-chitosan adhesive biomaterial caused no thermal damage to tissue. Examination of the cellular response at the material interface showed that 3T3 fibroblasts maintained their regular morphology with enhanced growth compared to films of both chitosan and its adhesive form. These results suggest that coalescence of UBM with a chitosan-based adhesive supports the development of biomaterial devices for sutureless wound closure that could enhance tissue repair and reconstruction.