Background Cancer remains one of the leading causes of mortality worldwide, with a continuously rising incidence. While cisplatin (Cis) is a widely used chemotherapeutic drug in cancer management, its clinical application is severely limited by chemotherapy –induced side effects, particularly hepatic and renal toxicity. Objective The study aimed to evaluate the protective effect of propolis and testosterone against cisplatin- induced hepatic-renal damage in male rats. Methods Thirty adult male white rats (200 and 220 g) were randomly divide into five groups (n = 6/group): (1) negative control group2; positive control group receiving cisplatin (7 mg/kg, IP single dose)3; testosterone and cisplatin (25 mg/kg, IP).4 Propolis and cisplatin (250 mg/kg propolis, orally);(5) testosterone, propolis and cisplatin (combined treatment). Results The serum in cisplatin treated group revealed a significant increase in creatinine, urea, ALT, AST and ALP. Moreover, significant decrease in SOD, and GSH and an increase MDA level in serum rat in comparison with control group. In addition. DNA damage was assessed in rat blood cells using alkaline comet assay. Administration of testosterone alone or propolis alone partially improved hepatic-renal damage and reduced DNA damage, while the combination of both showed superior protective effects. Histological examinations showed the hepatic renal damage that induced by cisplatin was attenuated by testosterone and propolis. Conclusion these results suggested that propolis and testosterone, whether alone or in combination may effectively attenuate cisplatin- induced hepatotoxicity and nephrotoxicity, potentially through their antioxidant and anti-inflammatory properties.
Introduction Chitinase-3-like protein 1 (CHI3L1) has been implicated in bone remodeling, but its relationship with bone turnover markers across different degrees of postmenopausal bone loss remains unclear. This study evaluated CHI3L1 together with CTX-1, NTX-1, and osteonectin (OSN) in Iraqi postmenopausal women with osteopenia (ON) and osteoporosis (OP). Materials and Methods Ninety postmenopausal women aged 45–65 years were classified into control, ON, and OP groups (n = 30 each) according to lumbar spine BMD and T-scores. Serum biomarkers were measured by ELISA. Group differences were assessed by one-way ANOVA with Tukey's HSD test. Pearson correlations were adjusted using the Benjamini–Hochberg false discovery rate, and multivariable regression was used to evaluate associations with BMD after adjustment for age, BMI, WHpR, and WHtR. ROC analysis assessed discriminatory performance. Results CHI3L1 and NTX-1 increased progressively from controls to ON and OP, whereas OSN decreased. CTX-1 was elevated in ON and OP versus controls but did not differ between ON and OP. CHI3L1, CTX-1, and NTX-1 were inversely associated with BMD, whereas OSN was positively associated (all p < 0.001). CTX-1 showed the highest AUC for ON versus controls (0.974), while NTX-1 showed the highest AUC for OP versus controls (0.999) and OP versus ON (0.968). Conclusion These biomarkers showed distinct associations with skeletal status and BMD. CHI3L1 may provide complementary information alongside established bone turnover markers, while NTX-1 exhibited the highest observed AUC for OP in this cohort. Larger independent studies are required for validation.
Feed conversion ratio (FCR) is a critical economic trait in broiler production, influencing both productivity and sustainability. In this study, an initial set of 2272 peak SNP records associated with FCR was retrieved from the Animal QTL Database and, following filtering and removal of duplicate/redundant records, 513 unique, non-redundant SNPs were retained for functional annotation using the Ensembl Variant Effect Predictor (VEP). These SNPs were mapped to 543 genes, allowing a detailed analysis of their genomic distribution and functional effects. The majority of SNPs were intron variants (54.0%), followed by downstream (17.7%), upstream (10.2%), and synonymous variants (6.5%). Missense variants (1.4%) were identified in biologically relevant genes such as ST3GAL6, NOX4, and TGFBR3, while 2.5% of SNPs were located in regulatory regions. Biotype classification showed that most variants (93.7%) occurred in protein-coding regions, with smaller proportions in lncRNA, enhancer, and miRNA regions. SNP clustering revealed potential genomic hotspots, with ST3GAL6 and DGKZ exhibiting exceptionally high densities, suggesting roles in FCR-related regulatory pathways. Functional enrichment analysis via g:Profiler identified significant associations with transcription factor binding motifs, including PU.1, NF-E4, and MAFA, as well as enrichment of catalytic activity and phosphatase-related complexes. These findings highlight potential genetic targets, such as ST3GAL6 and DGKZ, and regulatory networks, including catalytic activity (GO:0003824), that may influence FCR.
T-LAK cell-originated protein kinase (PBK/TOPK) is a serine/threonine kinase that is essential for DNA damage repair, cell division, mitosis, and tumor growth. Deleterious missense single nucleotide polymorphisms (nsSNPs) may alter the biological activity of PBK and structural stability, thus contributing to cancer progression. Therefore, this study aimed to use an integrated computational strategy to thoroughly identify and characterize pathogenic nsSNPs in the PBK gene and evaluate their potential clinical and therapeutic relevance in multiple myeloma. Additionally, compounds from Camellia sinensis were screened to identify potential inhibitors of three PBK mutants. Multiple computational approaches were employed to evaluate the drug-likeness and binding stability of these compounds. To identify missense variations, we employed multiple prediction tools, including SIFT, SNPs&GO, PolyPhen-2, PROVEAN, MetaSNP, and FATHMM. DeepREx-WS was used to assess sequence conservation, while MutPred2 and HOPE were employed for structural evaluation. SWISS-MODEL was used to construct structural models; HDOCK, PyRx 0.8, and PyMOL (v2.3.3) were used for molecular docking, virtual screening, and docked complex visualization; and CScape and Dr. Cancer were used to predict cancer-related alterations. Among the 421 missense SNPs identified in the NCBI dbSNP database, three variants — H158P, G188E, and G188R were found to be highly conserved across species, located in protein regions forming helices or strands, and associated with decreased protein stability. Structural analysis revealed that the three mutations altered the size, charge, and hydrophobicity of the PBK protein. Docking analyses revealed differences in the binding interactions and energies of TP53 with wild-type and mutant PBK proteins. Among the seven compounds screened from Camellia sinensis, Brassinolide was the most promising candidate for the PBK mutants H158P and G188R, whereas Castasterone showed the highest affinity for the G188E mutant, indicating its potential as a targeted therapeutic agent. Analysis of muTarget gene expression and Kaplan–Meier survival data indicated that PBK mutations were associated with specific gene expression changes. However, elevated PBK expression, rather than mutation status, was significantly correlated with poor prognosis in multiple myeloma. Our comprehensive in silico research provided insights into the structural and functional consequences of the identified PBK alterations. These findings support the hypothesis that PBK may serve as a potential prognostic biomarker and therapeutic target for treating multiple myeloma.
The need for sustainable construction material is rapidly increasing in recent past. To cope with this current situation the present study aims to develop bio-brick by inoculating ureolytic bacteria isolated from soil. The developed bio-brick showed 52.98% silt, clay with Plasticity index of 15.02%, Atterberg limits at 32.93% and 17.91% along with the water absorption capacity was found to be 8.52%. The compressive strength of the developed bio-brick increased to 7.15% with 4.49 MPa in comparison with control brick which was 4.19 MPa, thereby demonstrating enhanced mechanical performance compared to conventional fired clay bricks. The developed bio-brick demonstrated enhanced physical properties along with enhanced compressive strength of 7.15%. FTIR and XRD analyses confirmed the presence of silica-based mineral phases contributing to structural enhancement. X-ray diffractogram depicted peaks corresponding to the crystallographic planes of silica with highest diffraction at 26.75o. Additionally, the EDS analysis demonstrated that the bio-brick contained higher silica (46.83%). The SEM analysis highlighted significant bacterial colonization on the surface of the bio-brick, with clustered microbial formations, which might play important role in enhanced mechanical properties. Statistical analysis confirmed the significance of the observed improvement(p < 0.001). Metabolic profiling via TLC showed major bands at Rf values of 0.3, 0.4, 0.6, and 0.7 which were further identified via GC–MS with key metabolites, like Dodecyl acrylate and 2,4-Di-tert-butylphenol. The isolate was identified as Paenibacillus species via 16S rRNA sequencing. The developed bio-brick represents as one of the improved performance relative to conventional bricks with improved durability by balancing the strength and hydrophobic properties with minimal environmental effects. The findings highlight the potential of microbial-mediated bio-bricks as sustainable alternatives with reduced environmental impact, where microbial metabolites contribute to mineralization, binding, and hydrophobicity.
Background and aims Serum biomarkers that track mucosal inflammation in Crohn's disease (CD) beyond C-reactive protein (CRP) remain limited, particularly in Middle Eastern populations and in patients maintained on infliximab (IFX). We evaluated serum lipopolysaccharide-binding protein (LBP), interleukin-23 (IL-23) and interleukin-6 (IL-6) in active and IFX-maintained Iraqi CD patients versus healthy controls, and investigated the LBP-to-albumin ratio (LBP/Alb) as a novel composite biomarker. Methods In this cross-sectional case–control study (27 October 2025–25 March 2026) at Al-Najaf Gastrointestinal Tract Hospital, Iraq, 117 adults were enrolled: active CD (n = 32), IFX-CD (≥ 12 months maintenance; n = 35) and healthy controls (HC; n = 50). Serum LBP, IL-23 and IL-6 were measured by ELISA (BT Lab, Shanghai); CRP and albumin were measured on an SMT-120 analyser (Seamaty) in fixed-time mode. Activity was scored by the Harvey–Bradshaw Index (HBI); nutritional risk by MUST. Results LBP, IL-23 and IL-6 were significantly higher in both active CD and IFX-CD than in HC (all P < 0.001 after Bonferroni adjustment); pairwise differences between active CD and IFX-CD were not significant. IL-6 (AUC 0.982) and IL-23 (AUC 0.969) outperformed CRP (AUC 0.667) for discriminating all CD from HC. A combined IL-23 + IL-6 + CRP model reached AUC 0.995 (McFadden To address the possibility of overfitting and optimism in the diagnostic estimates, ROC performance was additionally evaluated by 5-fold stratified cross-validation in which standardisation and model fitting were performed within each training fold and applied to the held-out fold; cross-validated AUCs are reported with bootstrap 95% confidence intervals. Given the case–control design and the single-centre sample, these internal estimates are not a substitute for external validation, which remains necessary before any diagnostic application.R2 = 0.812). LBP/Alb correlated most strongly with HBI (ρ = 0.41), MUST (ρ = 0.50) and BMI (ρ = −0.46; all P < 0.001). Conclusions Serum LBP, IL-23 and IL-6 are markedly elevated in Iraqi CD patients and remain elevated during IFX maintenance, suggesting residual subclinical inflammation not captured by CRP alone. The LBP/Alb ratio is a promising accessible composite biomarker integrating bacterial-translocation and nutritional signals.
Background Chronic hepatitis C virus (HCV) infection is a growing health issue in Iraq, emphasizing the necessity to use precise diagnostic and predictive biomarkers to guide disease management. Although PCR-based detection of HCV viral load is highly sensitive, it is expensive and requires sophisticated facilities. Objectives To evaluate the diagnostic accuracy of serum microRNA-122 (miR-122), microRNA-221 (miR-221), and HCV core antigen (HCV core Ag) compared with PCR-based detection of HCV viral load, to determine their predictive value for treatment response, and to monitor their changes during direct-acting antiviral (DAA) therapy. Materials and Methods In this prospective study, 50 treatment-naive patients with chronic hepatitis C (CHC) and 50 healthy controls were recruited from Al-Ramadi Teaching Hospital and affiliated private clinics from January 2025 to December 2025. Each patient was assessed longitudinally at baseline, week 8, and week 12 of Sofosbuvir-Velpatasvir therapy, giving 150 patient-time observations. HCV RNA was measured using the GeneXpert system, HCV core antigen was measured using the Abbott Architect HCV Ag assay, and serum miR-122 and miR-221 were quantified using a separate RT-qPCR platform and normalized to miR-191. Results Serum miR-122 had excellent diagnostic accuracy (AUC = 0.92), with sensitivity and specificity of 89.3% and 86.0%, respectively. HCV core antigen demonstrated good diagnostic accuracy (AUC = 0.87). A combined model of miR-122 and HCV core antigen yielded superior diagnostic accuracy compared with either marker alone (AUC = 0.95). Baseline composite score predicted EOT virological response with good accuracy (AUC = 0.84). Significant correlations were found between HCV viral load and each of serum miR-122 (r = 0.78) and HCV core antigen (r = 0.82). Conclusion Serum miR-122 and HCV core antigen are clinically relevant complementary biomarkers for the diagnosis of chronic hepatitis C and for predicting on-treatment virological response in Iraqi patients. Although the microRNAs are themselves quantified by RT-qPCR, these findings support wider implementation of miRNA- and HCV core antigen-based testing as lower-cost complements, and in the case of HCV core antigen a potential alternative, to HCV RNA PCR for diagnosis and treatment monitoring in resource-constrained settings.
Antibiotic resistance is a growing global health concern, with poultry systems acting as important reservoirs of antibiotic resistance genes (ARGs). However, resistome and functional profiles of indigenous chickens raised under traditional systems remain underexplored. This study aimed to characterize the antibiotic resistome, virulence factor genes, and metabolic potential of gut microbiota in Indonesian Kedu chickens using a shotgun metagenomic approach. Digesta samples from five gastrointestinal segments of 21 healthy adult chickens were analyzed through high-throughput sequencing. ARGs were identified using the Comprehensive Antibiotic Resistance Database (CARD) and Antibiotic Resistance Genes Databases (ARDB), while virulence factors and functional genes were annotated using Virulence Factor Database (VFDB), Clusters of Orthologous Groups (COG), and Carbohydrate-Active EnZymes (CAZy) databases.Results revealed a diverse resistome dominated by multidrug resistance and efflux pump mechanisms, with prominent genes associated with fluoroquinolone, tetracycline, β-lactam, and glycopeptide resistance. The detection of clinically relevant ARGs suggests that genetic determinants associated with antimicrobial resistance are present in the gut microbiota of traditionally raised Kedu chickens, although metagenomic data alone cannot determine whether these genes are actively expressed or confer phenotypic resistance. Virulence factor analysis showed functions related to adherence, immune evasion, iron acquisition, quorum sensing, and efflux activity, reflecting strong microbial adaptability. Functional profiling demonstrated enrichment in translation, carbohydrate and amino acid metabolism, genome maintenance, and cell envelope biogenesis. Additionally, CAZyme analysis indicated a high capacity for complex polysaccharide degradation, supporting efficient utilization of fiber-rich traditional diets.In conclusion, this study provides a comprehensive metagenomic overview of antibiotic resistance and functional potential in Kedu chicken gut microbiota, emphasizing the importance of incorporating indigenous poultry into antimicrobial resistance surveillance within a One Health framework.
Background Lepidium sativum L. is a medicinal plant in the Brassicaceae family that has been used for the production of food and medicine. Scientists are becoming interested in it because of its rich phytochemical profile and ethnomedical uses. Nonetheless, a comprehensive understanding of its conventional use, bioactive components, pharmacological actions, and therapeutic significance is still crucial. Objective This review examines Lepidium sativum's traditional uses, phytochemical profile, pharmacological actions, and toxicological and safety considerations. Methods A literature search was conducted via PubMed, Scopus, Web of Science, and Google Scholar. This review was conducted in accordance with SANRA, and the findings were synthesized qualitatively. Results This review shows Lepidium sativum has a variety of pharmacological activities, including anti-inflammatory, analgesic, antimicrobial, antidiabetic, gastroprotective, hepatoprotective, nephroprotective, cardioprotective, neuroprotective, osteoprotective, wound-healing, reproductive, and anticancer effects. Bioactive components such as glucosinolates, alkaloids, phenolics, flavonoids, coumarins, and lignans are mostly responsible for these activities. These compounds affect cellular signaling, oxidative stress, inflammation, apoptosis, and metabolic pathways. Nevertheless, differences in phytochemical content, extraction techniques, dosage, bioavailability, and lack of standardization limit clinical translation. Traditional dosages of Lepidium sativum are usually harmless, but excessive doses or extended exposure to concentrated formulations may be harmful. Conclusion Lepidium sativum is a promising multipurpose medicinal plant that combines traditional knowledge with contemporary pharmacological research. Phytochemical bioactives and biological effects enable its growth as a source of functional foods, nutraceuticals, and medicinal agents. To determine its therapeutic potential, more research on molecular pathways, safety assessment, and clinical validation is necessary.
Background Probiotics are increasingly used in aquaculture to enhance fish survival, growth, and health, offering a sustainable approach to fish farming. Objective This study assessed the probiotic properties of Bacillus pumilus HFS2, isolated from the digestive tract of Heteropneustes fossilis. Method Among fourteen isolates, HFS2 was characterized using physiological, biochemical, and 16S rRNA analyses, and it's in vitro probiotic properties as well as in vivo safety were evaluated. Results The isolate was Gram-positive, rod-shaped, motile, and aerobic, showing positive results for methyl red, catalase and Voges–Proskauer tests, and a negative result for the indole test. It fermented dextrose, lactose, maltose, and mannitol with acid production but did not ferment sucrose. In vitro probiotic assessments showed that the strain tolerated a temperature range of 4–35 °C, survived at pH 2–5, and tolerated bile concentrations of 2.5–7.5%. The isolate demonstrated promising adhesion-related properties, including autoaggregation (66%), cell surface hydrophobicity (69% with xylene and 68% with toluene), and coaggregation with Lactococcus lactis (53%) and Staphylococcus arlettae (49%). It also exhibited inhibitory activity against fish pathogens such as Lactococcus garvieae, Aeromonas caviae, A. jandaei, A. veronii, and A. hydrophila. The isolate exhibited γ-hemolytic activity, strong biofilm-forming ability, and susceptibility to commonly used antibiotics, including ampicillin, vancomycin, erythromycin, tetracycline, chloramphenicol, and ciprofloxacin, while resistance observed only against cefotaxime. In vivo safety evaluation through intraperitoneal injection and immersion challenge at 108 CFU/mL indicated no pathogenic effects in H. fossilis. Conclusion These results suggest that B. pumilus HFS2 is a resilient and promising potential probiotic candidate for aquaculture applications.
Endophytic bacteria associated with Brassicaceae roots produce extracellular polysaccharides (EPS) that may inhibit carbohydrate-hydrolyzing enzymes related to antidiabetic properties. This study evaluated EPS produced by Brassicaceae root endophytes for inhibitory activity against carbohydrate-digesting enzymes and examined putative ligand–enzyme interactions using molecular docking. Endophytic bacteria were isolated from roots of cabbage, broccoli, Chinese broccoli, and pakcoy, phenotypically characterized, and identified by 16S rRNA gene sequencing. Crude EPS were extracted from bacterial cultures and quantified as dry weight, with total carbohydrate (glucose equivalents) and protein contents determined for compositional comparison. α-Glucosidase inhibitory activity was assessed in vitro using p-nitrophenyl-α-D-glucopyranoside as the substrate, and IC50 values were calculated from dose–response curves with acarbose as a positive control. In silico docking was performed against α-glucosidase (PDB: 2QMJ) using EPS-related monosaccharides, and pose reliability was evaluated by RMSD. Ten isolates produced EPS with yields ranging from 76.7 to 309.7 mg L−1. EPS-associated glucose equivalents ranged from 22.7 to 68.8 mg L−1 and protein from 22.8 to 46.7 mg L−1, indicating isolate/strain-dependent compositional variation. Two crude EPS samples showed the strongest α-glucosidase inhibition, with IC50 values of 121.16 ppm (Pseudomonas plecoglossicida AK8A4) and 168.72 ppm (Neobacillus drentensis AK4B2), whereas the remaining samples showed IC50 values >200 ppm; acarbose yielded an IC50 of 79.79 ppm. Docking produced stable poses (RMSD <2 Å) and predicted stronger binding for acarbose than for individual monosaccharides; among the latter, D-mannose showed the most favorable energy against α-glucosidase. Brassicaceae root bacterial endophytes produced crude EPS with potential α-glucosidase inhibitory activity, supporting further purification and structure–activity analysis to define active fractions and inhibitory mechanisms.
The aromatic rice cultivar Rojolele (Oryza sativa L. cv. Rojolele), prized for its superior organoleptic qualities, is highly susceptible to yellow stem borer (Scirpophaga incertulas), a pest causing significant yield losses in Asia. To address this vulnerability, we developed marker-free transgenic Rojolele lines expressing the cry1Ab gene using a double T-DNA vector system, eliminating reliance on antibiotic resistance markers. Agrobacterium-mediated transformation yielded 21 independent T0 lines, with PCR and Southern blot analysis confirming stable integration of cry1Ab in seven lines by the T3 generation. Immunostrip assays verified functional Cry1Ab protein expression, while bioassays demonstrated complete resistance in lines I.AR.4 and III.AR.5.3. Susceptible lines (I.AR.2, III.AR.5.2) exhibited variable transgene expressions, highlighting the importance of event selection. The marker-free strategy aligns with biosafety regulations, and the retained agronomic traits ensure compatibility with commercial cultivation. This study provides a sustainable solution to protect high-value aromatic rice, combining insect resistance with consumer-preferred qualities. Field trials and resistance management strategies, such as gene pyramiding, are recommended for future deployment.
Dengue virus (DENV) and chikungunya virus (CHIKV) co-infection poses a growing challenge in regions where both arboviruses co-circulate, highlighting the need for integrated vaccine strategies. Here, we designed a multi-epitope subunit vaccine candidate targeting conserved regions of the DENV NS1 protein and the CHIKV NSP1 protein using an immunoinformatics-based approach. Conserved CTL, HTL, and B-cell epitopes were selected on the basis of antigenicity, safety-related screening, and population coverage, then assembled with immunologically appropriate linkers and an N-terminal human β-defensin-2 adjuvant. The construct displayed favourable physicochemical features and acceptable structural quality after three-dimensional modeling and validation. Docking analysis indicated stable interaction with human TLR4, which was further examined by normal-mode analysis and 100-ns all-atom molecular dynamics simulations performed in AMBER v24 with the ff19SB force field. Trajectory analyses supported conformational stability of the vaccine-TLR4 complex, and MM/GBSA calculations suggested favourable binding energetics. Codon optimization supported expression feasibility in the E. coli pET-28a(+) system. In silico immune simulation further predicted induction of both humoral and cellular immune responses, with increased antibody production and immune-memory development. These results support the proposed construct as a rational candidate for further experimental evaluation toward a vaccine strategy against DENV-CHIKV co-infection.
Non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to non-alcoholic steatohepatitis (NASH) and fibrosis, yet current non-invasive tools lack accuracy in distinguishing these stages. This study aimed to evaluate the circulating miR-34a and miR-223 as biomarkers for NAFLD staging. In this cross-sectional study, 200 participants were equally divided into healthy individuals and patients with steatosis, NASH and fibrosis groups. Serum miRNA expression was measured by stem-loop RT-qPCR and miR-16 was used for normalization, while clinical parameters were measured to validate miRNAs. ANOVA and Kruskal-Wallis tests were used for group comparisons, while ROC analysis and multivariate regression were used to assess the diagnostic performance. Both miRNAs showed significant changes in mean expression across disease stages (p < 0.001). miR-34a increased from controls (1.42-fold) to NASH (41.28-fold), followed by a relative decline in fibrosis (12.84-fold), while miR-223 remained low in steatosis before rising sharply in NASH (42.17-fold). Both miRNAs correlated strongly with ALT, AST, platelet count, and lipid parameters (|r| > 0.6, p < 0.01). The combined miRNA panel accurately differentiated steatosis from NASH (AUC = 0.978; 96% sensitivity; 94% specificity). Both were independently associated with advanced disease (miR-34a: OR = 1.32, 95% CI: 1.18–1.48; miR-223: OR = 1.28, 95% CI: 1.15–1.42; p < 0.001), and patients in the highest quartiles had a 116-fold higher risk. The addition of both miRNAs to clinical models improved AUC from 0.812 to 0.912 (NRI = 0.267, p < 0.001). The expression patterns of miR-34a and miR-223 offered a practical non-invasive approach for staging of NAFLD.
Papillary thyroid carcinoma (PTC) is the most prevalent form of well-differentiated cancer of the thyroid gland. In the current study, we applied integrated bioinformatics analyses to introduce key genes with diagnostic and prognostic value, and decipher the signaling pathways involved in patients with PTC. We analyzed four integrated profiles from Gene Expression Omnibus (GEO) including, GSE58545, GSE3467, GSE29265, and GSE60542. GEO2R was utilized to analyze and detect differentially expressed genes (DEGs), and then the results of four datasets were integrated. Gene ontology (GO), KEGG-related pathway, protein-protein interaction (PPI) network, survival, and immunohistochemical assessment were performed by DAVID, ShinyGO, STRING, GEPIA, and Human Protein Atlas (HPA), respectively. In addition, we performed molecular docking of hub genes with 1615 FDA approved drugs. The findings of GO enrichment indicated that the up- and down-regulated genes were mostly participating in cell adhesion, extracellular region, and bicarbonate transport, proteinaceous extracellular receptor complex, respectively. Pathway enrichment indicated that the upregulated genes were linked with ECM-receptor interaction, and downregulated genes were largely involved in tyrosine metabolism and the JAK/STAT signaling pathway. The FN1, DPP, CD36, KIT, and ITGA2 proteins and hsa-mir-124-3p were identified as druggable target genes. According to docking analysis, Olysio, Gabapentin, Naldemedine, Imatinib and Enzacamene were drugs that exhibited strong interactions with the target proteins. The findings of the current study offer that FN1, DPP4, CD36, KIT, ITGA2 and hsa-miR-124-3p may be novel biosignatures and therapeutic targets for PTC. In addition, it was demonstrated that discovered pharmaceuticals may be employed as prospective PTC treatments.
The rise of antimicrobial resistance and emerging infectious diseases necessitates the discovery of novel antibacterial agents. Endophytic actinomycetes, especially Streptomyces species colonizing medicinal plant tissues, constitute a reservoir of structurally diverse bioactive metabolites that remains insufficiently characterized. This study reports the isolation and comprehensive characterization of an endophytic actinomycete, designated strain YBRX0, recovered from the root tissues of the Vietnamese medicinal plant Croton tonkinensis Gagnep. Strain identity was established through an integrated approach combining colony morphology, scanning electron microscopy, physiological and biochemical profiling, and 16S rRNA gene phylogenetic analysis. Bioactivity screening of the ethyl acetate fermentation extract employed agar well diffusion to assess antibacterial spectrum, with inhibitory potency quantified by broth microdilution. Antioxidant capacity was measured via DPPH radical scavenging, and secondary metabolite composition was profiled by GC–MS. The integrated characterization placed strain YBRX0 unambiguously within the genus. At 1 mg/mL, the ethyl acetate extract demonstrated broad-spectrum activity against both Gram-positive and Gram-negative pathogens, with MIC values ranging from 8 to 16 μg/mL. Antioxidant screening yielded an IC₅₀ of 197.26 ± 8.87 μg/mL. GC–MS tentatively identified Pyrrolopyrazine diketopiperazines and Benzeneacetamide as principal constituents. Collectively, these findings indicate that the crude extract of Streptomyces sp. YBRX0 exhibited notable antibacterial activity despite being an unfractionated mixture, supporting its potential as a promising source of bioactive metabolites for further bioprospecting and compound isolation efforts targeting drug-resistant pathogens.
This research aims to show the promising capacity of Streptomyces sp. BLC 17–3 to produce high β-mannanase enzymes and generate mannooligosaccharide (MOS) such as mannobiose, mannotriose, mannotetraose and mannopentaose when exposed to mannan polymers. Streptomyces sp. BLC 17–3 was isolated from the sponge (Rhabdastrella globostellata) Put4 obtained from the marine waters of Putus Island in Bitung, North Sulawesi, Indonesia. The characterization results showed that the peak enzyme activity was achieved at 50 mM sodium acetate, 6.0 pH, and 60 °C temperature on the seventh day of production with a value of 155.77 ± 3.21 U/mL. The SDS-PAGE and zymograms also showed that the size of the enzyme molecule was approximately ±34.8–49.1 kDa. Moreover, whole-genome sequencing was conducted to identify the genetic basis of MOS-synthesizing capabilities in the selected strain, followed by functional annotation of genes encoding mannan degradation and associated functions. The results showed an 8,248,862 Mb complete draft genome of the strain which comprised 111 predicted gene models. Gene annotation also provided important information about the location and function of protein-encoding genes. A total of 6 mannan degradation-related genes encoding mannanase-related metabolism were identified and the three-dimensional structures were predicted using AlphaFold 3. This characterization and modeling further enhanced the bioprospecting and development of this strain which exhibited efficient mannose metabolism. The results showed Streptomyces sp. BLC 17–3 as a promising microorganism for the future bioproduction of MOS which were discovered to have the capability of serving as a potential prebiotic substance to enhance digestion and promote health.
Introduction Alzheimer's disease is a progressive neurodegenerative disorder that is the leading cause of dementia worldwide. Genetic factors, particularly Apolipoprotein E (APOE) polymorphisms, are known to play a significant role in increasing susceptibility to Alzheimer's disease. The increasing number of publications related to APOE and Alzheimer's disease has prompted the need for bibliometric analysis and systematic reviews to comprehensively understand research developments and their genetic relationships. This study aims to analyze the global development of research on APOE polymorphisms in Alzheimer's disease through a bibliometric study and systematic review approach. Methods The study used a combined bibliometric and systematic review design. Data were obtained from the Scopus database for the period 2000–2025 using keywords Title-Abs-Key ((“APOE” Or “APOE E4” Or “Apolipoprotein E4”) And (“Alzheimer's disease”And (“Genetic Susceptibility”Or”Risk Factor”)) And (Limit-To (Doctype,”Ar”)) And (Limit-To(Language,”English”)) And Pubyear > 1999 And Pubyear < 2026. Bibliometric analysis was performed using VOSviewer and Microsoft Excel to evaluate publication trends, countries, institutions, journals, author collaborations, and co-occurrence keywords . A systematic review was conducted on 26 articles that met the inclusion criteria to evaluate the association of APOE polymorphisms with Alzheimer's risk. Results A total of 3824 articles from 718 publication sources were identified with an average citation of 51.51 per document. The United States was the country with the highest publication contribution. Keyword co-occurrence analysis showed that APOE4, genetics, and biomarkers were the main research themes. The results of the systematic review showed that APOE polymorphisms, especially rs429358 and rs7412, had a significant association with an increased risk of Alzheimer's disease in various ethnic populations with a very low p-value of up to 1E-320. Conclusion APOE polymorphisms play an important role in the genetic susceptibility of Alzheimer's disease and have the potential to be key biomarkers in early detection and the development of precision medicine in neurodegenerative diseases.
Clostridium difficile, a toxin-producing bacterium, can lead to conditions ranging from mild diarrhea to severe pseudomembranous colitis. Our research introduces an innovative strategy for developing a multi-epitope mRNA vaccine using in-silico methods targeting proteins involved in Clostridium difficile infection (CDI). Through computational models, we identified epitopes for B cells, helper T lymphocytes (HTL), and cytotoxic T lymphocytes (CTL) from protein sequences, assessing their immune response potential, allergenicity, toxicity, and autoimmune risk. The constructed 3D model underwent interaction docking and immune simulations, including evaluations of population coverage and physicochemical properties. Finally, molecular dynamics simulations were employed to test the vaccine's stability. Our findings suggest that this approach holds promise for creating a multi-epitope mRNA vaccine against C. difficile infection.
Background: Human metapneumovirus (HMPV) is a major cause of acute respiratory tract infections, particularly in young children, older adults, and immunocompromised individuals. Despite its significant clinical burden, no approved antiviral therapies or vaccines are currently available. This study aimed to identify potential RNA interference (RNAi)-based therapeutic candidates targeting the highly conserved fusion (F) gene of HMPV.Methods: An in silico pipeline was employed to design and evaluate small interfering RNA (siRNA) candidates targeting the HMPV F gene. A total of 869 siRNA sequences were initially generated using siDirect 2.1 software, which were sequentially filtered to 34 and then to 10 candidates based on sequence characteristics and predicted silencing efficiency. Molecular docking was performed to assess interactions between selected siRNAs and the human Argonaute-2 (AGO2) protein, followed by 100-ns molecular dynamics simulations to evaluate structural stability. Principal component analysis and free-energy landscape analyses were also performed.Results: Three siRNA candidates (F11, F19, and F26) demonstrated favorable RNAi characteristics, including high predicted silencing efficiency and strong target binding. Among them, F11 exhibited the highest sequence conservation across global HMPV strains, the highest melting temperature, favorable AGO2 interaction, and stable dynamic behavior. Principal component analysis indicated that F11 sampled the most constrained conformational subspace, which had a well-defined low-energy basin, thereby identifying it as the most promising candidate.Conclusions: This study identified F11 as the most promising siRNA candidate targeting the highly conserved HMPV fusion (F) gene, demonstrating strong potential as an RNAi-based therapeutic agent according to computational analyses. However, further in vitro and in vivo validation is required to confirm its efficacy and safety.
