Genes最新文献

Idiopathic pulmonary fibrosis (IPF) is a fatal and progressive lung disorder. Its pathological process involves persistent epithelial damage, ongoing inflammation, and dysregulated tissue repair. Currently, there are no effective treatment methods to improve patient survival. However, post-translational modifications (PTMs) have gradually garnered widespread attention. They are the processes by which various chemical groups are added to or removed from proteins' amino acid side chains or the N- or C-terminal ends of the polypeptide chain following synthesis. Additionally, they can regulate the energy supply of cells, regulate the cell cycle, and affect important signaling pathways such as TGF-β. This review systematically summarizes different categories of PTMs, organizes the PTMs involved in various injury stages of IPF, outlines the roles of different cells throughout the process, and analyzes future clinical diagnosis and treatment strategies as well as intervention targets for IPF, providing guiding significance for the systematic intervention of IPF in the future.

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Background/Objectives: This study presents the first molecular characterization of NF1 gene variants in Kazakhstani patients, expanding regional understanding of neurofibromatosis type 1 (NF1). The NF1 gene encodes neurofibromin, a tumor suppressor protein that regulates the MAPK signaling pathway; its inactivation results in NF1, a multisystem disorder with pigmentary and tumor manifestations. Methods: A total of 60 pediatric and young adult patients of University Clinic Aksai were selected based on Legius criteria and studied clinically; genetic variants of NF1 gene were determined with AmpliSeq for Illumina Myeloid Panel (next generation sequencing). Results: Pathogenic or likely pathogenic (with some variants of unknown significance) were detected in 58 of 60 (96.7%) patients. Among them, 27 (46.6%) carried point variants, 21 (36.2%) had genomic deletions, 3 (5.2%) had duplications, 3 (5.2%) insertions, and 4 (6.9%) had exon-intron splicing site variants. Notably, all patients with duplication insertions and splicing variants presented with plexiform neurofibromas. Conclusions: The study defines the first variant spectrum in a Kazakhstani population, confirming genotype-phenotype correlations consistent with European cohorts (l.). These data highlight the predominance of structural and splicing alterations in patients with plexiform neurofibromas and support the integration of molecular testing into clinical management of NF1 in Kazakhstan.

Objectives: This study aimed to determine whether chromosomal mosaicism in blastocysts is associated with a distinct morphokinetic signature.

Methods: Preimplantation genetic testing for aneuploidy (PGT-A) was performed on 182 human embryos via trophectoderm biopsy on day 5 and analyzed by next-generation sequencing. Embryos were classified as euploid (n = 55), mosaic (n = 39: 21 low-grade, 18 high-grade), or aneuploid (n = 88), of which 18 with concurrent mosaicism. Prior to biopsy, embryos were cultured in a time-lapse system (EmbryoScope), and 12 morphokinetic parameters were assessed, including pronuclei fading (tPNf), cleavage times (t2-t9), morula formation (tM), blastulation start (tSB), and full blastocyst formation (tB). These parameters were compared according to ploidy status.

Results: Patients with euploid and mosaic embryos were comparable in terms of maternal age, ART indication and embryo quality (p > 0.05). In contrast, aneuploid embryos were obtained from older patients and had lower morphological grades. Mosaic embryos showed delayed tPNf (24.8 ± 6.5 vs. 22.8 ± 2.3 h, p = 0.03) and t2 (27.6 ± 6.6 vs. 25.4 ± 2.5 h, p = 0.02) compared to euploid embryos, mainly attributable to low-grade mosaic embryos. Whole-chromosome mosaicism, but not segmental mosaicism, was associated with delayed embryo development at several intermediate cleavage time points (t3, t4, t6, t7 and t9). Aneuploid embryos showed significant delays at later stages versus euploid embryos, particularly aneuploid embryos with mosaicism at t7 (56.6 ± 8.3 vs. 52 ± 5.6 h, p = 0.02), t8 (59.1 ± 9.6 vs. 54.8 ± 6.7 h, p = 0.04), tM (90.3 ± 7.7 vs. 83.6 ± 8.2 h, p = 0.006) and tB (113.0 ± 11.6 vs. 106.6 ± 8.9 h, p = 0.03).

Conclusions: Mosaic embryos exhibit delays in early development (tPNf, t2) but reach later morphokinetic milestones at rates similar to euploid embryos. In contrast, aneuploid embryos, especially those with mosaicism, exhibit marked developmental delays at later stages (t7, t8, tM, tB).

Background: This research sought to screen potential biomarkers in diagnosing breast diseases and elucidating their immune-related mechanisms. Methods: Three datasets were attained from the Gene Expression Omnibus (GEO) database. LIMMA package and weighted gene co-expression network analysis (WGCNA) were used to ascertain differentially expressed genes (DEGs) and key modules in benign breast disease (BBD) and breast cancer (BC). The intersecting genes underwent functional enrichment analysis. Three machine learning (ML) methods (encompassing LASSO regression, random forest, and support vector machine recursive feature elimination (SVM-RFE)) were implemented to select core genes. The diagnostic performance of the core genes was evaluated by comparing their expression levels, plotting receiver operating characteristic (ROC) curves, and constructing a Nomogram. The TCGA-BRCA dataset was used to estimate the prognostic capability of the core genes among individuals with BC. Finally, the IC infiltration was ascertained utilizing the CIBERSORT algorithm. Results: In total, 2579 DEGs were identified in BBD. WGCNA exhibited that the 1652 genes in green and pink modules were strongly correlated with BBD. In BC, 2742 DEGs were identified. The turquoise and red modules contained 7286 genes exhibiting strong correlations with BC. After intersecting, 41 common genes were obtained, which were predominantly enriched in immune and inflammation regulation pathways. Through integrated screening with three ML algorithms, Arrestin Domain Containing 1 (ARRDC1) and ATPase Sarcoplasmic/Endoplasmic Reticulum Ca²⁺ Transporting 2 (ATP2A2) were identified as core genes. The ROC curve exhibited that the AUC for the two genes was greater than 0.8. The calibration curve of the nomogram signified a strong alignment between the anticipated risk and detected results. Survival analysis in TCGA-BRCA showed that the high expression of the two genes exhibited a significantly positive association with unfavorable prognosis. Immune infiltration analysis further demonstrated the dysregulation of multiple immune cells in patient samples. Conclusions:ARRDC1 and ATP2A2 are strongly linked to BBD and BC. These findings might enhance our comprehension of the pathogenesis and progression of both BBD and BC, offering prospective biological biomarkers and therapeutic targets for clinical treatment.

Background/Objectives: Licorice (Glycyrrhiza glabra L.) is a highly important medicinal plant that is widely used in China owing to its active ingredients. Its main active components are flavonoids, including liquiritigenin, liquiritin and licochalcone A. The hairy roots (HRs) induced by Agrobacterium rhizogenes are a commonly used chassis in synthetic biology to enhance the production of active compounds in medicinal plants. Methods: A biosynthesis system to acquire the active ingredients of G. glabra was established using an HR culture system. It employed a transcriptome analysis to identify the change in gene expression following treatment with methyl jasmonate (MeJA). Results: After 28 days of suspension culture, the biomass of HRs increased by approximately 34.5-fold and reached 1.83 g/100 mL flask. Treatment with MeJA significantly increased the contents of liquiritigenin, liquiritin, and glabridin in the HRs. The transcriptome data indicated that MeJA activated the flavonoid biosynthetic pathway genes in the HRs, which was largely consistent with the qRT-PCR results. Furthermore, the overexpression of the GgCHS6 gene substantially increased the content of flavonoids in HRs. Conclusions: Collectively, this study established an HR system to biosynthesize the active ingredients of G. glabra using metabolic engineering and genetic engineering techniques and provides several valuable candidate genes for further functional study.

Background: Diabetic nephropathy (DN) is a leading cause of end-stage renal disease, arising from complex interactions between metabolic, hemodynamic, and genetic factors. Among candidate genes, vascular endothelial growth factor A (VEGFA) has been extensively investigated due to its role in endothelial homeostasis and microvascular complications of diabetes. The present study aimed to examine the association of VEGFA polymorphisms with DN in a Greek population and to perform a comprehensive meta-analysis of available evidence. Methods: A case-control study was conducted, including 197 patients with type 2 diabetes mellitus (T2DM) and DN, 155 diabetic patients without nephropathy, and 246 healthy controls. Ten tagging single-nucleotide polymorphisms (SNPs) across VEGFA were genotyped. Statistical analyses employed the generalized odds ratio (OR_G). To contextualize these findings, a meta-analysis of 13 eligible studies was performed, encompassing 7520 cases, 6951 diabetic controls, and 1718 healthy controls. Results: Of the tested variants in the present case-control study, only rs833070 was significantly associated with DN across all comparisons. Nine VEGFA variants were evaluated in meta-analysis, with rs2146323 showing a protective effect (allelic OR = 0.85; 95% CI: 0.76-0.95), while other variants yielded non-significant associations. Conclusions: Overall, the data suggest that VEGFA polymorphisms, particularly rs833070 and rs2146323, contribute to genetic susceptibility to DN, although population-specific differences and heterogeneity across studies remain substantial. Future research in large, ethnically diverse cohorts with functional analyses is warranted to clarify causal mechanisms and enable the integration of VEGFA genetic variation into risk stratification and personalized therapeutic strategies.

Background/objectives: The sarcoplasmic reticulum Ca²⁺-ATPase 1 (Atp2a1) is a key regulator of calcium homeostasis and muscle relaxation, yet its roles in fish remain poorly understood.

Methods: We investigated the structural characteristics, phylogenetic relationships, and transcriptional regulation of atp2a1 in Acrossocheilus fasciatus, a stream-dwelling cyprinid sensitive to environmental fluctuations.

Results: Bioinformatic analyses revealed that the 991-aa Atp2a1 protein is highly conserved among teleosts but exhibits divergence from mammals in the Cation_ATPase_N domain and transmembrane regions TM3, TM9, and TM10. Phylogenetic analysis clustered A. fasciatus most closely with Onychostoma macrolepis. Tissue-specific qRT-PCR demonstrated predominant expression in skeletal muscle, followed by testis, brain, heart, and gill. Promoter prediction identified binding motifs for KLF9, CTCF, MAZ, KLF5, ONECUT3, and HOXB13. qRT-PCR analysis showed that long-term cold acclimation (16 °C vs. 24 °C) markedly downregulated atp2a1 expression (ANOVA, p < 0.05, n = 3), whereas moderate flow velocity (2 BL·s^-1 vs. 0 BL·s^-1) significantly upregulated it (ANOVA, p < 0.05, n = 3). Alternative splicing analysis based on RNA-seq data further revealed a corresponding decrease and increase in skipped exon (SE) inclusion under cold and flow conditions, respectively (P_adj < 0.05).

Conclusions: These results further raise the possibility that the regulatory complexity of atp2a1 contributes to adaptation of teleosts under fluctuating environments.

Background: Cystic echinococcosis (CE) is a globally distributed zoonosis triggered by the larval stage of Echinococcus granulosus (E. granulosus), impacting humans and an extensive array of mammalian intermediate hosts. EGR-01664 is the major egg antigen of E. granulosus, but almost nothing is currently known about the function of EGR-01664 from E. granulosus.

Methods: This study aimed to investigate the E. granulosus EGR-01664 gene (GenBank ID: 36337379), and the recombinant EGR-01664 protein was expressed successfully. Next, the transcription of the EGR-01664 gene across various developmental stages of E. granulosus was analyzed. Its spatial expression patterns in adult worms and protoscoleces were characterized using both quantitative PCR (qPCR) and immunofluorescence assays. Furthermore, the immunomodulatory effects of rEGR-01664 on cell proliferation, nitric oxide production, and cytokine secretion were examined by co-culturing the recombinant protein with canine PBMCs.

Results: The rEGR-01664 could be recognized by sera from dogs infected with E. granulosus. Immunofluorescence assay (IFA) localization revealed the protein's presence in the epidermis of protoscoleces, the adult epidermis, and some parenchymal tissues. qPCR revealed that EGR-01664 mRNA levels were significantly higher in protoscoleces compared to adults (p < 0.0001). At a concentration of 20 μg/mL, rEGR-01664 could significantly activate the transcription and expression of IL-10, TGF-β1, IL-17A, and Bax in canine PBMCs. However, with an increase in concentration, it inhibited the expression of IFN-γ, Bcl-2, GSDMD, IL-18, and IL-1β. These results suggest that the EGR-01664 gene plays a crucial role in the development, parasitism, and reproduction of E. granulosus. In vitro studies have shown that rEGR-01664 protein regulates the immune regulation function of canine PBMCs, suggesting its potential as a vaccine adjuvant or immunotherapy target.

Conclusions: EGR-01664 may modulate canine PBMC functions to regulate host immune responses, thereby facilitating our understanding of how E. granulosus EGR-01664 contributes to the mechanism of parasitic immune evasion.

Background: Seed shattering enhances ecological adaptation in perennial grasses but severely limits harvestable seed yield in forage crops. Psathyrostachys juncea is an important perennial forage species in arid and cold regions, yet the genetic basis of its seed shattering remains largely unknown. Here we asked which genomic regions and biological pathways underlie natural variation in seed shattering in P. juncea, and whether cellulose synthase (CESA)-mediated cell-wall formation contributes to abscission-zone strength.

Results: We evaluated seed shattering in a diverse association panel of P. juncea across four environment--year combinations and performed a genome-wide association study (GWAS) using genotyping-by-sequencing single-nucleotide polymorphism (SNP) markers. The analysis identified 36 significant SNP loci distributed on multiple chromosomes, consistent with a highly polygenic and environment-responsive architecture. Candidate-gene annotation highlighted pathways related to cell-wall biosynthesis, hormone signaling and sugar transport. Notably, in the BT23SHT environment a cluster of association signals on chromosome 3D co-localized with several genes annotated as cellulose synthase (CESA). Abscission-zone transcriptome profiling and qRT-PCR at 7, 14, 21 and 28 days after heading revealed that CESA genes, including TraesCS3D02G010100.1 located near the lead SNP Chr3D_3539055, showed higher early expression in low-shattering lines and a decline toward baseline in high-shattering lines. Comparative analyses placed P. juncea CESA proteins within a broadly conserved but lineage-divergent framework among grasses.

Conclusion: Together, these results define the genetic landscape of seed shattering in P. juncea and nominate cellulose-biosynthetic genes on chromosome 3D as promising targets for marker-assisted selection of low-shattering, high-seed-yield forage cultivars.