Background Cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) is a pivotal immune checkpoint regulator implicated in the development of autoimmune diseases, including type 1 diabetes (T1D). Objective This study examined the association of three CTLA-4 polymorphisms—rs231775 (+49 A/G), rs5742909 (−318 C/T), and rs3087243 (CT60 A/G)—along with haplotype structure and linkage disequilibrium (LD), with T1D susceptibility in Iraqi children. Methods In this case–control study, 100 pediatric T1D patients and 100 age- and sex-matched healthy controls were enrolled. Genotyping was performed using TETRA-ARMS PCR and allele-specific PCR. Genotype and allele distributions were evaluated under different genetic models using odds ratios (ORs) with 95% confidence intervals (CIs). Haplotype and LD analyses were conducted using the expectation–maximization algorithm. The study adhered to STROBE guidelines. Results The rs3087243 G allele was strongly associated with higher odds of T1D risk (OR = 4.05, 95% CI: 2.56–6.41, P < 0.001). The rs5742909 T allele also showed a significant association (OR = 2.25, 95% CI: 1.36–3.71, P < 0.001). No significant association was observed for rs231775. Haplotype analysis showed that the C-G-G and T-G-G haplotypes were more frequent among patients and exhibited nominal associations with T1D susceptibility. Moderate to strong LD was detected among the studied variants. After Bonferroni correction (α = 0.0167), only rs3087243 and rs5742909 remained significant. Conclusion The present findings suggest that CTLA-4 polymorphisms, particularly rs3087243 and rs5742909, may contribute to susceptibility to T1D in Iraqi children. The observed haplotype patterns and LD structure provide preliminary evidence of potential genetic relationships within the CTLA-4 locus; however, these secondary findings should be considered exploratory and require validation in larger independent cohorts.
Once regarded as transcriptional noise, long non-coding RNAs (lncRNAs) are now recognized as pivotal regulators of inflammation and host immune responses. In this context, comprehensive profiling of lncRNAs is especially relevant in heterogeneous disorders like asthma, where biologically distinct endotypes often converge into similar clinical presentations. Deploying lncRNAs as endotype-specific biomarkers offers a promising strategy to address heterogeneity in asthma, refine patient stratification, and guide the development of targeted therapies beyond conventional phenotype-based disease management. This comprehensive review outlines the multifaceted roles of lncRNAs across all stages of asthma pathogenesis, highlighting their function as molecular conduits linking environmental triggers to airway inflammation, driving hyperresponsiveness, and promoting persistent tissue remodelling. In addition, it discusses systematic discovery-to-validation pipelines for asthma-associated lncRNAs and finally addressing current limitations and their emerging potential as diagnostic and therapeutic candidates.
Colorectal cancer (CRC) is a prevalent malignancy globally, and the distinct roles of the integrin subunit β (ITGB) family in CRC are not fully understood. In this systematic exploration, we aimed to systematically characterize the expression patterns and explore the potential prognostic and immunological relevance of ITGB family members in CRC. The data from TCGA combined with online tumor analysis databases (UALCAN, HPA, cBioPortal, GeneMANIA, TIMER, et al) were utilized to analyze differential expression, diagnostic and prognostic value, genetic alteration, potential function pathway and immune cell infiltration of ITGBs in CRC. We found that all ITGB family members exhibited genetic alterations in CRC cohorts. At the transcript level, ITGB4/5 and ITGB8 were significantly upregulated, whereas ITGB3/7 were downregulated in CRC. At the protein level (CPTAC via UALCAN), ITGB2/5 were elevated, while ITGB1/3/4/6 and ITGB7 were reduced in colon adenocarcinoma. In contrast, ITGB5 exhibited consistent upregulation at both mRNA and protein levels. Receiver operating characteristic curve analysis highlighted ITGB3/4/5/7 and ITGB8 as potential biomarkers for distinguishing CRC from normal tissues, although these findings are hypothesis-generating and require further validation. Furthermore, ITGB1/3/5 and ITGB7 were significantly correlated with clinicopathologic features such as cancer clinical stage, cancer infiltration and metastasis. Survival analyses indicated that high ITGB7 and low ITGB6 mRNA levels were associated with shorter overall survival. To complement our bioinformatic predictions, we performed preliminary expression validation of ITGB5 in CRC cell lines and clinical tissues via qPCR and immunohistochemistry (IHC). Functional enrichment analyses of ITGB-associated gene programs highlighted processes related to cell adhesion, gene expression regulation, immune regulation, and angiogenesis. In addition, immune infiltration analyses revealed significant correlations between ITGB expression (especially ITGB2/3/7) and multiple immune-cell subsets. This comprehensive bioinformatic correlation analysis reveals statistical associations between ITGB family expression and clinical prognosis as well as tumor immune infiltration in CRC.
Zinc (Zn) is an indispensable micronutrient that plays a pivotal role in plant growth, development, and productivity by serving as a structural, catalytic, and regulatory cofactor for numerous enzymes and proteins. It is essential for the activity of carbonic anhydrase, RNA polymerase, alcohol dehydrogenase, and Cu/Zn-superoxide dismutase, thereby regulating photosynthesis, chlorophyll biosynthesis, protein synthesis, auxin metabolism, membrane stability, antioxidant defence, pollen development, and grain quality. However, the increasing prevalence of zinc deficiency in agricultural soils, driven by intensive cultivation and unsustainable nutrient management, has become a major constraint to crop productivity and nutritional security. The present study aimed to isolate, characterize, and evaluate efficient zinc-solubilizing bacterial strains for enhancing zinc bioavailability, zinc uptake, and rice productivity under zinc-deficient soil conditions. Among the eight bacterial isolates obtained from rice rhizosphere, Enterobacter ludwigii ZnPSBJ-23 and Enterobacter cloacae ZnPSBJ-6 exhibited superior zinc-solubilizing ability against insoluble zinc compounds, including zinc oxide (ZnO), zinc carbonate (ZnCO3), and zinc phosphate [Zn3(PO4)2]. The solubilization efficiencies of ZnPSBJ-23 and ZnPSBJ-6 were 340% and 286% for ZnO, 246% and 220% for Zn3(PO4)2, and 200% and 180% for ZnCO3, respectively. Morphological characterization revealed that both isolates produced round, entire, flat colonies with a shiny appearance. Inoculation of rice seedlings with these isolates significantly enhanced plant growth, yield attributes, zinc uptake, and grain zinc accumulation compared with the uninoculated control. Grain yield increased by 90% and 80% following inoculation with ZnPSBJ-23 and ZnPSBJ-6, respectively. The highest Zinc Mobilization Efficiency Index (ZnMEI) was recorded for ZnPSBJ-23 (0.98), followed by ZnPSBJ-6 (0.93), demonstrating their superior capacity to mobilize native soil zinc. These findings indicate that E. ludwigii ZnPSBJ-23 and E. cloacae ZnPSBJ-6 possess considerable potential as bioinoculants for improving zinc bioavailability, enhancing rice productivity, and promoting zinc biofortification in zinc-deficient soils. Future studies should focus on multilocation field validation, formulation development, rhizosphere colonization efficiency, and elucidation of the molecular mechanisms governing microbial zinc solubilization and plant–microbe interactions.
Background Familial Mediterranean Fever (FMF) is a monogenic autoinflammatory disorder. While gut microbiome alterations have been recognized in FMF, circulating cell-free microbial DNA signatures remain insufficiently characterized. This exploratory pilot study evaluated the circulating microbial DNA profiles in Egyptian children with FMF compared to healthy controls. Methods Peripheral blood was collected from 10 pediatric FMF patients in remission and 10 healthy controls matched according to age category and sex. The V3–V4 regions of the 16S rRNA gene were sequenced using an Illumina platform. Reads were processed using an OTU-based pipeline (97% identity). Results Alpha-diversity measures showed no significant differences between the groups. The unweighted UniFrac distance revealed significant differences in microbial composition (p = 0.01498), whereas the weighted UniFrac distance did not (p = 0.955). Taxa such as Pseudomonas, Delftia, and Weissella showed descriptive enrichment in FMF, whereas commensal lineages (Romboutsia, Blautia, and Lactobacillus) were more abundant in the control group. Conclusion These exploratory findings indicate distinct circulating microbial DNA profiles in pediatric FMF. However, given the low-biomass sample type, unsequenced negative controls, and pilot sample size, these results represent preliminary hypothesis-generating associations rather than validated clinical biomarkers.
The auxin/indole-3-acetic acid (AUX/IAA) proteins are key repressors in the auxin signaling pathway, playing crucial roles in growth, development, and stress adaptation in trees. In this study, we conducted a genome-wide identification of the AUX/IAA gene family in Populus wilsonii, revealing 35 members designated as PwiAUX/IAAs. All encoded proteins contain the typical conserved domains (I–IV), with lengths ranging from 145 to 368 amino acids, and are predicted to localize to the nucleus. Phylogenetic analysis classified these members into two major subgroups (A and B), showing a conserved clustering relationship with their counterparts in Arabidopsis. Chromosomal mapping indicated that the 35 genes are unevenly distributed across 11 chromosomes, with chromosomes 2 and 6 harboring the highest number (5 genes each). Tandem and segmental duplications were identified as key drivers of family expansion. Promoter analysis revealed that all members possess diverse cis-acting elements associated with hormone responses and abiotic stress. Expression profiling demonstrated distinct tissue- and developmental stage-specific expression patterns. For instance, PwiAUX/IAA4, PwiAUX/IAA13, and PwiAUX/IAA14 showed phloem-specific high expression, PwiAUX/IAA27 was prominently expressed in leaves, while the progressively increasing expression of PwiAUX/IAA35 with stem aging suggests its potential involvement in secondary growth, providing a candidate gene for future functional investigation. This study provides the first systematic analysis of the AUX/IAA gene family in P. wilsonii, offering valuable insights into its auxin signaling regulatory network and providing candidate gene resources for future molecular breeding applications in forest trees.
Epigenetic modifications, particularly DNA methylation, are implicated in the pathogenesis of metabolic syndrome (MetS). However, the methylation status of GFPT2, which encodes a key enzyme in the hexosamine biosynthetic pathway, remains poorly understood. Therefore, this study aimed to investigate the promoter methylation status of the GFPT2 gene in individuals with MetS and evaluate its association with clinical characteristics and its diagnostic potential. Whole blood samples were collected from 95 Iranian patients with MetS and 105 healthy controls. GFPT2 promoter methylation was quantified using the MethylQESD technique, a bisulfite conversion-independent method for the quantitative analysis of DNA methylation. Our findings revealed that GFPT2 promoter methylation was significantly higher in patients with MetS than in healthy controls (35.07 ± 19.72% vs. 25.39 ± 19.76%, P < 0.001). Receiver operating characteristic analysis yielded an area under the curve (AUC) of 0.693 (95% CI: 0.617–0.770, P < 0.001), with a sensitivity of 78.94% and a specificity of 72.38% at the optimal cutoff value. Among patients with MetS, GFPT2 promoter methylation was positively correlated with BMI (r = 0.716, 95% CI: 0.602–0.802, P < 0.001) and waist circumference (r = 0.500, 95% CI: 0.332–0.637, P < 0.001), whereas no significant associations were observed with age, sex, smoking status, physical activity, fasting blood glucose, blood pressure, HDL cholesterol, or triglyceride levels (P > 0.05). Despite its modest discriminatory performance, GFPT2 promoter methylation may serve as a complementary biomarker within a multi-marker panel, although further studies are needed to validate its clinical utility.
As the most prominent family of small guanosine triphosphate (GTP)-binding proteins in plants, RAB GTPases are essential regulators of intracellular trafficking, cytokinesis, autophagy, growth and development, as well as mediators of plant-pathogen interactions and environmental (abiotic and biotic) stress responses. While structurally and functionally characterised in various crops, the RAB GTPase gene family and its functional roles have remained unexplored in allopolyploid canola (Brassica napus).This study identified 205 BnRAB (RAB GTPases in Brassica napus) genes, representing the largest RAB GTPase family reported to date in a eudicot species. Phylogenetic and sequence analyses classified these genes into eight distinct groups (RABA–H), with members within each group exhibiting highly conserved gene structures and protein motif distributions. Evolutionary analysis suggested that the diversity of the BnRAB family may reflect the shared evolutionary history of the Brassica lineage, including ancient whole-genome triplication and subsequent hybridisation of Brassica rapa and Brassica oleracea.Transcriptomic analysis of publicly available RNA-Seq datasets indicates preferential expression of RAB GTPases in reproductive tissues and developing seeds, suggesting their potential roles in regulating agronomically important traits such as pollen development, seed set, and storage compound accumulation, thereby providing candidate targets for improving yield stability and stress resilience in canola. This is further supported by protein domain identification, promoter cis-element profiling and subcellular localisation prediction studies, which together associate these proteins with male gametophyte and seed development, and signalling pathways for light, phytohormones and various biotic (infection with Sclerotinia sclerotiorum, Leptosphaeria maculans, Leptosphaeria biglobosa) and abiotic (salinity, cold, drought and heat) stresses. These findings are based on computational and transcriptomic analyses, and further research is needed to establish the link between RAB GTPases and agronomically important traits in canola. Collectively, this research provides a comprehensive catalogue of BnRABs, providing a valuable genomic resource for future functional studies investigating the molecular mechanisms that drive plant development and stress tolerance.
The chitinase gene family in plants plays a significant role in plant defense, conferring resistance to biotic and abiotic stresses through the hydrolysis of β-1,4-glycosidic linkages in chitin. Potato is highly susceptible to fungal pathogens such as Fusarium spp. and Alternaria alternata, as well as drought stress due to its shallow root system. To better understand its defense mechanisms, we performed a genome-wide analysis and identified 31 chitinase genes in the potato genome. These genes were classified into glycosyl hydrolase families GH18 and GH19 and grouped into four classes (I, III, IV, and V). Gene structure analysis revealed that most potato chitinases contain few or no introns, supporting rapid transcription under stress conditions. Promoter analysis showed that class I chitinases carry the highest number of cis-acting elements associated with drought and pathogen responses. Phylogenetic and synteny analyses demonstrated evolutionary conservation and diversification between potato and tomato chitinases. Expression profiling using qRT-PCR analysis of representative genes indicated that the analyzed class I chitinase gene was strongly induced under both drought and chitin treatments, whereas the analyzed class V chitinase gene showed high responsiveness to chitin treatment but was suppressed under drought conditions. The analyzed class III and class IV chitinase genes displayed distinct expression patterns, suggesting potential functional specialization. Together, these findings highlight the potential contribution of the analyzed chitinase genes, particularly the class I representative gene, to potato stress responses and suggest that chitin application could be used as an effective elicitor of defense responses. Stress-responsive promoters identified in this study may provide tools for improving potato stress tolerance.
