Buccal Administration of a Zika Virus Vaccine Utilizing 3D-Printed Oral Dissolving Films in a Mouse Model.

Over the years, research regarding the Zika virus has been steadily increasing. Early immunization for ZIKV is a priority for preventing complications such as microencephaly and Guillain-Barré syndrome (GBS). Unlike traditional vaccination approaches, oral dissolving films (ODFs) or mucoadhesive film technology is an emerging, exciting concept that can be used in the field of pharmaceuticals for vaccine design and formulation development. This attractive and novel method can help patients who suffer from dysphagia as a complication of a disease or syndrome. In this study, we investigated a microparticulate Zika vaccine administered via the buccal route with the help of thin films or oral dissolving films (ODFs) with a prime dose and two booster doses two weeks apart. In vitro, the ODFs displayed excellent physiochemical properties, indicating that the films were good carriers for vaccine microparticles and biocompatible with the buccal mucosa. In vivo results revealed robust humoral (IgG, subtypes IgG1 and IgG2a) and T-cell responses (CD4+/CD8+) for ZIKV-specific immunity. Both the Zika MP vaccine and the adjuvanted Zika MP vaccine affected memory (CD45R/CD27) and intracellular cytokine (TNF-α and IL-6) expression. In this study, ZIKV vaccination via the buccal route with the aid of ODFs demonstrated great promise for the development of pain-free vaccines for infectious diseases.

Identification of Differentially Expressed Genes and Protein-Protein Interaction in Patients With COVID-19 and Diabetes Peripheral Neuropathy: A Bioinformatics and System Biology Approach.

The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact globally, resulting in a higher death toll and persistent health issues for survivors, particularly those with pre-existing medical conditions. Numerous studies have demonstrated a strong correlation between catastrophic COVID-19 results and diabetes. To gain deeper insights, we analysed the transcriptome dataset from COVID-19 and diabetic peripheral neuropathic patients. Using the R programming language, differentially expressed genes (DEGs) were identified and classified based on up and down regulations. The overlaps of DEGs were then explored between these groups. Functional annotation of those common DEGs was performed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Bio-Planet, Reactome, and Wiki pathways. A protein-protein interaction (PPI) network was created with bioinformatics tools to understand molecular interactions. Through topological analysis of the PPI network, we determined hub gene modules and explored gene regulatory networks (GRN). Furthermore, the study extended to suggesting potential drug molecules for the identified mutual DEG based on the comprehensive analysis. These approaches may contribute to understanding the molecular intricacies of COVID-19 in diabetic peripheral neuropathy patients through insights into potential therapeutic interventions.

Transcranial Doppler in the Detection of Cerebral Vasospasm After Subarachnoid Hemorrhage.

Background Transcranial Doppler (TCD) is a simple, noninvasive, nonionizing, portable technique but not widely practiced to detect cerebral vasospasm after subarachnoid hemorrhage (SAH). Objective The aim of this study was to assess the performance of TCD in the detection of cerebral vasospasm in patients with SAH considering CT angiography (CTA) as a gold standard. Methods and material This cross-sectional study included 50 patients with acute SAH admitted to the National Institute of Neurosciences & Hospital (NINS & H), Dhaka, Bangladesh, from February to June 2021. The neurological status, severity of SAH, and initial CT findings were recorded. All patients were screened for cerebral vasospasm with TCD on the 4th, 7th, 10th, and 14th days after the event. Screening of cerebral vasospasm by CTA was done on the 14th day of the event or earlier if TCD suggested vasospasm. Results The mean age of the participants was 51.4 ±13.4 years (mean ± SD), and females were predominant (N=29, 58%). CTA detected cerebral vasospasm in 18 (36%) participants, but TCD could detect it in only 13 (26%) cases. Among the participants who had no vasospasm by CTA, all but one were also found to have no vasospasm by TCD. The agreement between TCD and CTA in detecting cerebral vasospasm was significant (p<0.001, κ=0.726). TCD shows good specificity (96.9%) and positive predictive value (92.8%), but sensitivity (72.2%) and negative predictive value (81.6%) were comparatively lower. Overall, the diagnostic accuracy of TCD in detecting cerebral vasospasm was 88%. Conclusions Although compared to CTA, TCD is a highly specific but less sensitive tool in detecting vasospasm, TCD remains a reliable screening tool for detecting vasospasm following SAH.

Securing IoT Networks from DDoS Attacks Using a Temporary Dynamic IP Strategy.

The progression of the Internet of Things (IoT) has brought about a complete transformation in the way we interact with the physical world. However, this transformation has brought with it a slew of challenges. The advent of intelligent machines that can not only gather data for analysis and decision-making, but also learn and make independent decisions has been a breakthrough. However, the low-cost requirement of IoT devices requires the use of limited resources in processing and storage, which typically leads to a lack of security measures. Consequently, most IoT devices are susceptible to security breaches, turning them into "Bots" that are used in Distributed Denial of Service (DDoS) attacks. In this paper, we propose a new strategy labeled "Temporary Dynamic IP" (TDIP), which offers effective protection against DDoS attacks. The TDIP solution rotates Internet Protocol (IP) addresses frequently, creating a significant deterrent to potential attackers. By maintaining an "IP lease-time" that is short enough to prevent unauthorized access, TDIP enhances overall system security. Our testing, conducted via OMNET++, demonstrated that TDIP was highly effective in preventing DDoS attacks and, at the same time, improving network efficiency and IoT network protection.

Intranasal Immunization for Zika in a Pre-Clinical Model.

Humans continue to be at risk from the Zika virus. Although there have been significant research advancements regarding Zika, the absence of a vaccine or approved treatment poses further challenges for healthcare providers. In this study, we developed a microparticulate Zika vaccine using an inactivated whole Zika virus as the antigen that can be administered pain-free via intranasal (IN) immunization. These microparticles (MP) were formulated using a double emulsion method developed by our lab. We explored a prime dose and two-booster-dose vaccination strategy using MPL-A® and Alhydrogel® as adjuvants to further stimulate the immune response. MPL-A® induces a Th1-mediated immune response and Alhydrogel® (alum) induces a Th2-mediated immune response. There was a high recovery yield of MPs, less than 5 µm in size, and particle charge of -19.42 ± 0.66 mV. IN immunization of Zika MP vaccine and the adjuvanted Zika MP vaccine showed a robust humoral response as indicated by several antibodies (IgA, IgM, and IgG) and several IgG subtypes (IgG1, IgG2a, and IgG3). Vaccine MP elicited a balance Th1- and Th2-mediated immune response. Immune organs, such as the spleen and lymph nodes, exhibited a significant increase in CD4+ helper and CD8+ cytotoxic T-cell cellular response in both vaccine groups. Zika MP vaccine and adjuvanted Zika MP vaccine displayed a robust memory response (CD27 and CD45R) in the spleen and lymph nodes. Adjuvanted vaccine-induced higher Zika-specific intracellular cytokines than the unadjuvanted vaccine. Our results suggest that more than one dose or multiple doses may be necessary to achieve necessary immunological responses. Compared to unvaccinated mice, the Zika vaccine MP and adjuvanted MP vaccine when administered via intranasal route demonstrated robust humoral, cellular, and memory responses. In this pre-clinical study, we established a pain-free microparticulate Zika vaccine that produced a significant immune response when administered intranasally.

Caregiver Narratives of Children with Autism Spectrum Disorder: Exploring Symptom Recognition, Diagnosis, and Interventions.

The diagnosis of autism spectrum disorder (ASD) poses myriad challenges for families, yet there is a scarcity of research focusing on their journey from recognizing initial anomalies to implementing interventions. This qualitative study examines how caregivers in Sylhet, Bangladesh, perceive and manage ASD in their children, including early symptom identification, diagnostic processes, and intervention strategies. Data for this study were collected through semi-structured interviews, case studies, and observations involving 22 caregivers of children with ASD. Participants were chosen using purposive-convenience sampling, and data collection continued until interpretive saturation was achieved. The study findings unveil nuanced caregiver perceptions of ASD causation, influenced by sociocultural factors, religious beliefs, and genetic predispositions. These determinants wield significant influence over treatment modalities and the child's developmental trajectory. Importantly, the prevalence of supernatural beliefs and myths often surpasses biomedical explanations, highlighting gaps in awareness, educational outreach, and understanding of ASD. Nevertheless, religious beliefs and rituals concurrently serve as adaptive coping mechanisms, offering solace amidst uncertainty. Furthermore, a striking observation emerges: despite parents frequently identifying anomalies in their children within a 24-month, a substantial delay of 3 to 5 years persists between initial symptom recognition and formal diagnosis. This delay predominantly stems from caregiver hesitancy driven by societal stigmatization, familial dismissal attitudes, and limited diagnostic and specialized services. This study highlights the challenging diagnostic journey and caregiving for children with ASD in Bangladesh, stressing the need for systemic improvements in services, awareness, and research to enhance the well-being of individuals with ASD.

Production and Release of Proinflammatory Mediators by the Cockroach Allergen Bla g 1 via a Shared Membrane-Destabilization Mechanism.

The cockroach allergen Bla g 1 encloses an exceptionally large hydrophobic cavity, which allows it to bind and deliver unsaturated fatty acid ligands. Bla g 1-mediated delivery of naturally occurring (nMix) ligands has been shown to destabilize lipid membranes, contributing to its digestive/antiviral functions within the source organism. However, the consequences of this activity on Bla g 1 allergenicity following human exposure remain unknown. In this work, we show that Bla g 1-mediated membrane disruption can induce a proinflammatory immune response in mammalian cells via two complementary pathways. At high concentrations, the cytotoxic activity of Bla g 1 induces the release of proinflammatory cytosolic contents including damage-associated molecular patterns (DAMPs) such as heat-shock Protein-70 (HSP70) and the cytokine interleukin-1 (IL-1ß). Sublytic concentrations of Bla g 1 enhanced the ability of phospholipase A2 (PLA2) to extract and hydrolyze phospholipid substrates from cellular membranes, stimulating the production of free polyunsaturated fatty acids (PUFAs) and various downstream inflammatory lipid mediators. Both of these effects are dependent on the presence of Bla g 1's natural fatty-acid (nMix) ligands with CC50 values corresponding to the concentrations required for membrane destabilization reported in previous studies. Taken together, these results suggest that mechanisms through which Bla g 1-mediated lipid delivery and membrane destabilization could directly contribute to cockroach allergic sensitization.

Protective effects of growth hormone - releasing hormone antagonists in the lungs of septic mice.

Growth hormone-releasing hormone antagonists (GHRHAnt) have been associated with antitumor and antioxidative activities. The present study investigates for the first time the effects of those compounds towards pro-inflammatory cytokine expression in a murine model of cecal ligation and puncture (CLP) - induced sepsis. The results indicate that GHRHAnt JV-1-36 significantly suppressed IL-1α, IL-6, and pSTAT3 activation in septic lungs. Moreover, GHRHAnt treatment reduced bronchoalveolar lavage fluid (BALF) protein concentration, suggesting a protective effect of that compound in sepsis-induced lung edema. Based on those findings, it is suggested that GHRHAnt may represent an exciting new therapeutic possibility in sepsis-induced endotoxemia and lung injury.

Key role of plankton species and nutrients on biomagnification of PAHs in the micro-food chain: A case study in plateau reservoirs of Guizhou, China.

There is considerable inconsistency in results pertaining to the biomagnification of PAHs in aquatic systems. Zooplankton specifically play an important role controlling the fate and distribution of organic contaminants up the food chain, particularly in large plateau reservoirs. However, it remains largely unknown how secondary factors affect the magnification of organic compounds in zooplankton. The present study assessed plankton species and nutrients affecting the trophic transfer of PAHs through the micro-food chain in plateau reservoirs, Guizhou Province China. Results show soluble ∑PAHs range from 99.9 - 147.3 ng L-1, and concentrations of ∑PAHs in zooplankton range from 1003.2 - 22441.3, with a mean of 4460.7 ng g-1 dw. Trophic magnification factors (TMFs) > 1 show biomagnifications of PAHs from phytoplankton to zooplankton. The main mechanisms for trophic magnification > 1 are 1) small Copepoda, Cladocera and Rotifera are prey for larger N. schmackeri and P. tunguidus, and 2) the δ15N and TLs of zooplankton are increasing with the increasing nutrients TN, NO3- and CODMn. As a result, log PAHs concentrations in zooplankton are positively correlated with the trophic levels (TLs) of zooplankton, and log BAFs of the PAHs in zooplankton are increasing with increasing TLs and log Kow. Temperature further enhances TMFs and biomagnifications of PAHs as noted by temperature related reductions in δ15N. There are also available soluble PAHs in the water column which are assimilated with increasing phytoplankton biomass within the taxa groups, diatoms, dinoflagellates and chlorophytes. Notable TMFs of PAHs in zooplankton in Guizhou plateau reservoirs are not significantly affected by phytoplankton and zooplankton biomass dilutions. The present study demonstrates the important roles of species selection, nutrients and temperature in the environmental fate of PAHs in freshwaters.

Flotillin-2 dampens T cell antigen-sensitivity and functionality.

T cell receptor (TCR) engagement triggers T cell responses, yet how TCR-mediated activation is regulated at the plasma membrane remains unclear. Here, we report that deleting the membrane scaffolding protein Flotillin-2 (Flot2) increases T cell antigen sensitivity, resulting in enhanced TCR signaling and effector function to weak TCR stimulation. T cell-specific Flot2-deficient mice exhibited reduced tumor growth and enhanced immunity to infection. Flot2-null CD4 + T cells exhibited increased T helper 1 polarization, proliferation, Nur77 induction, and phosphorylation of ZAP70 and LCK upon weak TCR stimulation, indicating a sensitized TCR-triggering threshold. Single cell-RNA sequencing suggested that Flot2 - null CD4 + T cells follow a similar route of activation as wild-type CD4 + T cells but exhibit higher occupancy of a discrete activation state under weak TCR stimulation. Given prior reports that TCR clustering influences sensitivity of T cells to stimuli, we evaluated TCR distribution with super-resolution microscopy. Flot2 ablation increased the number of surface TCR nanoclusters on naïve CD4 + T cells. Collectively, we posit that Flot2 modulates T cell functionality to weak TCR stimulation, at least in part, by regulating surface TCR clustering. Our findings have implications for improving T cell reactivity in diseases with poor antigenicity, such as cancer and chronic infections.

Characterization, histopathology and immunogenicity of the lumpy skin disease virus isolated during 2019-20 in Bangladesh.

Introduction: Lumpy skin disease (LSD) is a highly contagious vector-borne viral disease of cattle. LSD has emerged in Bangladesh in 2019, causing significant economic losses due to its high morbidity and mortality. This research was designed to isolate, identify, and assess the immunogenicity of LSD virus (LSDV) using nodular tissue samples obtained from affected cattle during the 2019-20 outbreak across nine districts of Bangladesh. Methods: To determine the presence of LSDV in nodular tissues, we initially used iiPCR and PCR, followed by histopathological examination. 151 were positive via iiPCR and PCR among the 180 collected samples. The PCR positive 151 samples were then inoculated into 10-day-old embryonated chicken eggs via the CAM route to isolate LSDV, confirmed through PCR. Subsequently, partial sequencing and phylogenetic analysis of the P32 gene were performed to determine the origin of the circulating LSDV strain. The immunogenicity of selected LSDV strains was assessed through an ELISA test. Results: The PCR results revealed a distinct positive band at 192 bp in both the nodular tissue samples and the LSDV isolated from chicken embryo inoculations. Microscopic analysis of the nodular lesions revealed thickening of the epidermis, ballooning degeneration of keratinocytes, and proliferation of follicular epithelia. Additionally, mononuclear infiltration was observed at the demarcation line between infected and healthy tissue, with necrosis of muscular tissues beneath the epidermis. The LSDV isolate from Bangladesh exhibited a close genetic relationship with LSDV strains isolated from neighboring and other regional countries including India, Myanmar, and Mongolia. This observation strongly suggests the possibility of a transboundary spread of the LSD outbreak in Bangladesh during 2019-2020. The results of the immunogenicity test showed that the serum antibody titer remained at a protective level for up to 18 months following secondary immunization with inactivated LSDV antigen. This finding suggests that the inactivated LSDV antigen could be a potential vaccine candidate to protect cattle in Bangladesh against LSDV. Conclusion: In conclusion, our research successfully isolated, identified, and characterized LSDV in cattle nodular tissues from the 2019-20 outbreak in Bangladesh. Furthermore, it provided insights into the probable origin of the circulating strain and investigated a potential vaccine candidate to protect cattle in the region from LSDV.

A visual dataset for recognition of rice varieties.

This article presents a comprehensive dataset sourced from various markets across Bangladesh, highlighting 20 distinct rice varieties predominantly consumed locally. The dataset encompasses a diverse range of rice strains, including Subol Lota, Bashmoti (Deshi), Ganjiya, Shampakatari, Sugandhi Katarivog, BR-28, BR-29, Paijam, Bashful, Lal Aush, BR-Jirashail, Gutisharna, Birui, Najirshail, Pahari Birui, Polao (Katari), Polao (Chinigura), Amon, Shorna-5, and Lal Binni. Using a smartphone camera, low-resolution images capturing the essence of each rice variety were meticulously obtained, resulting in a total of 4,730 images with a non-uniform distribution. The dataset also includes augmented data, totaling 23,650 images. This precisely curated dataset holds significant promise and utility, showcasing diverse attributes, including the unique representation of 20 rice varieties, each characterized by distinct colors, sizes, and potential applications within the agricultural sector.

Analyzing molecular signatures in preeclampsia and fetal growth restriction: Identifying key genes, pathways, and therapeutic targets for preterm birth.

Background: Intrauterine growth restriction (IUGR) and preeclampsia (PE) are intricately linked with specific maternal health conditions, exhibit shared placental abnormalities, and play pivotal roles in precipitating preterm birth (PTB) incidences. However, the molecular mechanism underlying the association between PE and IUGR has not been determined. Therefore, we aimed to analyze the data of females with PE and those with PE + IUGR to identify the key gene(s), their molecular pathways, and potential therapeutic interactions. Methods: In this study, a comprehensive relationship analysis of both PE and PE + IUGR was conducted using RNA sequence datasets. Using two datasets (GSE148241 and GSE114691), differential gene expression analysis via DESeq2 through R-programming was performed. Gene set enrichment analysis was performed using ClusterProfiler, protein‒protein interaction (PPI) networks were constructed, and cluster analyses were conducted using String and MCODE in Cytoscape. Functional enrichment analyses of the resulting subnetworks were performed using ClueGO software. The hub genes were identified under both conditions using the CytoHubba method. Finally, the most common hub protein was docked against a library of bioactive flavonoids and PTB drugs using the PyRx AutoDock tool, followed by molecular dynamic (MD) simulation analysis. Pharmacokinetic analysis was performed to determine the ADMET properties of the compounds using pkCSM. Results: We identified eight hub genes highly expressed in the case of PE, namely, PTGS2, ENG, KIT, MME, CGA, GAPDH, GPX3, and P4HA1, and the network of the PE + IUGR gene set demonstrated that nine hub genes were overexpressed, namely, PTGS2, FGF7, FGF10, IL10, SPP1, MPO, THBS1, CYBB, and PF4. PTGS2 was the most common hub gene found under both conditions (PE and PEIUGR). Moreover, the greater (-9.1 kcal/mol) molecular binding of flavoxate to PTGS2 was found to have satisfactory pharmacokinetic properties compared with those of other compounds. The flavoxate-bound PTGS2 protein complex remained stable throughout the simulation; with a ligand fit to protein, i.e., a RMSD ranging from ∼2.0 to 4.0 Å and a RMSF ranging from ∼0.5 to 2.9 Å, was observed throughout the 100 ns analysis. Conclusion: The findings of this study may be useful for treating PE and IUGR in the management of PTB.

XAI-FusionNet: Diabetic foot ulcer detection based on multi-scale feature fusion with explainable artificial intelligence.

Diabetic foot ulcer (DFU) poses a significant threat to individuals affected by diabetes, often leading to limb amputation. Early detection of DFU can greatly improve the chances of survival for diabetic patients. This work introduces FusionNet, a novel multi-scale feature fusion network designed to accurately differentiate DFU skin from healthy skin using multiple pre-trained convolutional neural network (CNN) algorithms. A dataset comprising 6963 skin images (3574 healthy and 3389 ulcer) from various patients was divided into training (6080 images), validation (672 images), and testing (211 images) sets. Initially, three image preprocessing techniques - Gaussian filter, median filter, and motion blur estimation - were applied to eliminate irrelevant, noisy, and blurry data. Subsequently, three pre-trained CNN algorithms -DenseNet201, VGG19, and NASNetMobile - were utilized to extract high-frequency features from the input images. These features were then inputted into a meta-tuner module to predict DFU by selecting the most discriminative features. Statistical tests, including Friedman and analysis of variance (ANOVA), were employed to identify significant differences between FusionNet and other sub-networks. Finally, three eXplainable Artificial Intelligence (XAI) algorithms - SHAP (SHapley Additive exPlanations), LIME (Local Interpretable Model-agnostic Explanations), and Grad-CAM (Gradient-weighted Class Activation Mapping) - were integrated into FusionNet to enhance transparency and explainability. The FusionNet classifier achieved exceptional classification results with 99.05 % accuracy, 98.18 % recall, 100.00 % precision, 99.09 % AUC, and 99.08 % F1 score. We believe that our proposed FusionNet will be a valuable tool in the medical field to distinguish DFU from healthy skin.

Influence of folic acid and vitamin B12 supplementation on arsenic methylation: A double-blinded, placebo-controlled trial in Bangladeshi children.

BACKGROUND: Inorganic arsenic is metabolized to monomethyl- (MMAs) and dimethyl- (DMAs) species via one-carbon metabolism (OCM); this facilitates urinary arsenic elimination. OCM is influenced by folate and vitamin B12 and previous randomized control trials (RCTs) showed that folic acid (FA) supplementation increases arsenic methylation in adults. This RCT investigated the effects of FA + B12 supplementation on arsenic methylation in children, a key developmental stage where OCM supports growth. METHODS: A total of 240 participants (8-11 years, 53 % female) drinking from wells with arsenic concentrations > 50 µg/L, were encouraged to switch to low arsenic wells and were randomized to receive 400 µg FA + 5 µg B12 or placebo daily for 12-weeks. Urine and blood samples were collected at baseline, week 1 (only urine) and week 12. Generalized estimated equation (GEE) models were used to assess treatment effects on arsenic species in blood and urine. RESULTS: At baseline, the mean ± SD total blood and urinary arsenic were 5.3 ± 2.9 µg/L and 91.2 ± 89.5 µg/L. Overall, total blood and urine arsenic decreased by 11.7% and 17.6%, respectively, at the end of follow up. Compared to placebo, the supplementation group experienced a significant increase in the concentration of blood DMAs by 14.0% (95% CI 5.0, 25.0) and blood secondary methylation index (DMAs/MMAs) by 0.19 (95% CI: 0.09, 0.35) at 12 weeks. Similarly, there was a 1.62% (95% CI: 0.43, 20.83) significantly higher urinary %DMAs and -1.10% (95% CI: -1.73, -0.48) significantly lower urinary %MMAs in the supplementatio group compared to the placebo group after 1 week. The direction of the changes in the urinary %iAs, %MMAs, and %DMAs at week 12 were consistent with those at week 1, though estimates were not significant. Treatment effects were stronger among participants with higher baseline blood arsenic concentrations. Results were consistent across males and females, and participants with higher and lower folate and B12 status at baseline. CONCLUSION: This RCT confirms that FA + B12 supplementation increases arsenic methylation in children as reflected by decreased MMAs and increased DMAs in blood and urine. Nutritional interventions may improve arsenic methylation and elimination in children, potentially reducing arsenic toxicity while also improving nutritional status.

Genetic association of Interleukin-17A polymorphism in Bangladeshi patients with breast and cervical cancer: a case-control study with functional analysis.

BACKGROUND: Breast and cervical cancer are the two leading cancers in terms of incidence and mortality. Previous studies reported different interleukins, including interleukin-17A (IL-17A) to be responsible for the development and progression of these malignancies. Therefore, we speculated that the variants in this gene might be associated with these cancer developments in Bangladeshi population. For evaluating the hypothesis, we investigated the association of IL-17A rs3748067 polymorphism with the susceptibility of both breast and cervical cancer. METHODS: This case-control study was performed on 156 breast cancer patients, 156 cervical cancer patients, and 156 controls using the tetra-primer amplification refractory mutation system-polymerase chain reaction. The statistical software package SPSS (version 25.0) was applied for analyses. The genetic association was measured by the odds ratio (OR) and 95% confidence intervals (CIs). A statistically significant association was considered when p-value ≤ 0.05. Functional analysis was performed using GEPIA and UALCAN databases. RESULTS: From the calculation of the association of IL-17A rs3748067 with breast cancer, it is found that no genotype or allele showed a statistically significant association (p>0.05). On the other hand, the analysis of IL-17A rs3748067 with cervical cancer demonstrated that CT genotype showed a significant association (CT vs. CC: OR=1.79, p=0.021). In the overdominant model, CT genotype also revealed a statistically significant association with cervical cancer, which is found to be statistically significant (OR=1.84, p=0.015). CONCLUSION: Our study summarizes that rs3748067 polymorphism in the IL-17A gene may be associated with cervical cancer but not breast cancer in Bangladeshi patients. However, we suggest studies in the future with a larger sample size.

Antifungal plant flavonoids identified in silico with potential to control rice blast disease caused by Magnaporthe oryzae.

Rice blast disease, caused by the fungus Magnaporthe oryzae, poses a severe threat to rice production, particularly in Asia where rice is a staple food. Concerns over fungicide resistance and environmental impact have sparked interest in exploring natural fungicides as potential alternatives. This study aimed to identify highly potent natural fungicides against M. oryzae to combat rice blast disease, using advanced molecular dynamics techniques. Four key proteins (CATALASE PEROXIDASES 2, HYBRID PKS-NRPS SYNTHETASE TAS1, MANGANESE LIPOXYGENASE, and PRE-MRNA-SPLICING FACTOR CEF1) involved in M. oryzae's infection process were identified. A list of 30 plant metabolites with documented antifungal properties was compiled for evaluation as potential fungicides. Molecular docking studies revealed that 2-Coumaroylquinic acid, Myricetin, Rosmarinic Acid, and Quercetin exhibited superior binding affinities compared to reference fungicides (Azoxystrobin and Tricyclazole). High throughput molecular dynamics simulations were performed, analyzing parameters like RMSD, RMSF, Rg, SASA, hydrogen bonds, contact analysis, Gibbs free energy, and cluster analysis. The results revealed stable interactions between the selected metabolites and the target proteins, involving important hydrogen bonds and contacts. The SwissADME server analysis indicated that the metabolites possess fungicide properties, making them effective and safe fungicides with low toxicity to the environment and living beings. Additionally, bioactivity assays confirmed their biological activity as nuclear receptor ligands and enzyme inhibitors. Overall, this study offers valuable insights into potential natural fungicides for combating rice blast disease, with 2-Coumaroylquinic acid, Myricetin, Rosmarinic Acid, and Quercetin standing out as promising and environmentally friendly alternatives to conventional fungicides. These findings have significant implications for developing crop protection strategies and enhancing global food security, particularly in rice-dependent regions.

Tea (Camellia sinensis) cultivated in three agro-ecological regions of Bangladesh: Unveiling the variability of methylxanthine, bioactive phenolic compound, and antioxidant activity.

Tea (Camellia sinensis) is a widely consumed beverage known for its numerous health benefits, largely attributed to its rich content of quality determining secondary metabolites such as methylxanthine compounds and bioactive phenolic compounds. The goal of this study was to find out variations of the levels of methylxanthines, bioactive phenolic compounds, and antioxidant activity in methanolic and hot water extracts of 129 tea samples grown in three different ecological regions of Bangladesh named Panchagar, Sylhet, and Chattogram. Methylxanthine and bioactive phenolic compounds were determined by using HPLC-DAD, and the antioxidant profile was analysed by UV-vis spectrophotometric methods for methanol and hot water extracts of tea leaves. The IC50 values showed the trend as Panchagar > Sylhet > Chattogram and Sylhet > Chattogram > Panchagar for water and methanol extract, respectively. The results revealed significant (p < 0.05) variations in the levels of methylxanthines content: Panchagar > Chattogram > Sylhet. Caffeine was significantly higher (103.02 ± 5.55 mg/g of dry extract) in the methanolic extract of tea leaves of Panchagar district and lower (53.33 ± 4.30 mg/g of dry extract) in the hot water extract of Sylhet district. Panchagar and Chattogram possessed significantly (p < 0.05) higher catechin content for methanol (57.01 ± 5.50 mg/g dry extract) and hot water (55.23 ± 4.11 mg/g dry extract) extracts, respectively. The utilization of canonical discriminant functions yielded highly favorable outcomes in the classification of tea from three distinct cultivation origins in Bangladesh, relying on their inherent features. This study demonstrated the potential effects of geographical variations on the bioactive compounds and antioxidant properties of tea, emphasizing the importance of regional differences in tea cultivation for optimizing its health benefits as well as dispersing tea cultivation across the country.

Herbal Spices as Food and Medicine: Microscopic Authentication of Commercial Herbal Spices.

Herbal spices are an agricultural commodity, economically very important and beneficial in primary healthcare in the food and medicine sectors. Herbal spices are used as food flavoring agents as well as in phytotherapies throughout the world and have nutritive benefits. The food and medicine industries widely employ artificial or natural adulteration to retard the deterioration and utilization of these adulterants in food and medicine products has given rise to significant apprehension among consumers, primarily stemming from the potential health risks that they pose. Thus, their characterization for the purpose of identification, origin, and quality assurance is mandatory for safe human consumption. Here, we studied 22 samples of commonly traded herbal spices that belong to 20 different genera and 21 species comprising 14 families, investigated macroscopically or organoleptically as well as histologically under microscopic examination. In this study, we provide details on organoleptic features including appearance, taste, odor, color, shape, size, fractures, types of trichomes, and the presence of lenticels among the examined herbal spices and these features have great significance in the detection of both natural as well as artificial deterioration. In terms of microscopic characterization, each examined plant part comprising different anatomical characteristics has taxonomic importance and also provides useful information for authentication from natural adulterants. Furthermore, the studied taxa were also described with nutritive and therapeutic properties. For condiments, herbal beverages and medicinal purposes, different herbal parts such as leaves, floral buds, seeds, fruit, and accessory parts like mericarp, rhizome, bulbs, and bark were used and commercially traded. Similarly, in this study, the leaves of Cinnamomum tamala and Mentha spicata, the floral buds of Syzygium aromaticum, the seeds of Amomum subulatum, Brassica nigra, Punica granatum, Myristica fragrans, Phyllanthus emblica, and Elettaria cardamomum, the mericarp of Coriandrum sativum, and Cuminum cyminum were observed. As a result, we show the potential of herbal spices as a source of many valuable phytochemicals and essential nutrients for food, nutraceutical, and homoeopathic medicine.

Selection of lansoprazole from an FDA-approved drug library to inhibit the Alzheimer's disease seed-dependent formation of tau aggregates.

The efficacy of current treatments is still insufficient for Alzheimer's disease (AD), the most common cause of Dementia. Out of the two pathological hallmarks of AD amyloid-ß plaques and neurofibrillary tangles, comprising of tau protein, tau pathology strongly correlates with the symptoms of AD. Previously, screening for inhibitors of tau aggregation that target recombinant tau aggregates have been attempted. Since a recent cryo-EM analysis revealed distinct differences in the folding patterns of heparin-induced recombinant tau filaments and AD tau filaments, this study focused on AD seed-dependent tau aggregation in drug repositioning for AD. We screened 763 compounds from an FDA-approved drug library using an AD seed-induced tau aggregation in SH-SY5Y cell-based assay. In the first screening, 180 compounds were selected, 72 of which were excluded based on the results of lactate dehydrogenase assay. In the third screening with evaluations of soluble and insoluble tau, 38 compounds were selected. In the fourth screening with 3 different AD seeds, 4 compounds, lansoprazole, calcipotriene, desogestrel, and pentamidine isethionate, were selected. After AD seed-induced real-time quaking-induced conversion, lansoprazole was selected as the most suitable drug for repositioning. The intranasal administration of lansoprazole for 4 months to AD seed-injected mice improved locomotor activity and reduced both the amount of insoluble tau and the extent of phosphorylated tau-positive areas. Alanine replacement of the predicted binding site to an AD filament indicated the involvement of Q351, H362, and K369 in lansoprazole and C-shaped tau filaments. These results suggest the potential of lansoprazole as a candidate for drug repositioning to an inhibitor of tau aggregate formation in AD.