Search Results (577)

Myocardial infarction (MI) remains one of the most common cardiovascular diseases and a leading cause of morbidity and mortality worldwide. In recent years, natural polymeric patches have attracted increasing attention as a promising therapeutic platform for myocardial tissue repair. This study explored the fabrication and evaluation of screen-printed electrodes (SPEs) on chitosan film as a novel platform for cardiac patch applications. Chitosan is a biodegradable and biocompatible natural polymer that provides an ideal substrate for SPEs, providing mechanical stability and promoting cell adhesion. Silver ink was employed to enhance electrochemical performance, and the electrodes exhibited strong adhesion and structural integrity under wet conditions. Mechanical testing and swelling ratio analysis were conducted to assess the patch’s physical robustness and aqueous stability. Silver ink was employed to enhance electrochemical performance, which was evaluated using cyclic voltammetry. In vitro, electrical stimulation through the chitosan–SPE patch significantly increased the expression of cardiac-specific genes (GATA-4, β-MHC, troponin I) in bone marrow mesenchymal stem cells (BMSCs), indicating early cardiogenic differentiation potential. In vivo, the implantation of the chitosan–SPE patch in a rat MI model demonstrated good tissue integration, preserved myocardial structure, and enhanced ventricular wall thickness, indicating that the patch has the potential to serve as a functional cardiac scaffold. These findings support the feasibility of screen-printed electrodes fabricated on chitosan film substrates as a cost-effective and scalable platform for cardiac repair, offering a foundation for future applications in cardiac tissue engineering. Full article

Background: Gastric cancer (GC) represents a significant global health burden with considerable heterogeneity in clinical and molecular behavior. The anatomical site of tumor origin—proximal versus distal—has emerged as a determinant of prognosis and response to therapy. The aim of this paper is to elucidate the transcriptional and regulatory differences between proximal gastric cancer (PGC) and distal gastric cancer (DGC) through master regulator (MR) analysis. Methods: We analyzed RNA-seq data from TCGA-STAD and microarray data from GEO (GSE62254, GSE15459). Differential gene expression and MR analyses were performed using DESeq2, limma, corto, and RegEnrich pipelines. A harmonized matrix of 4785 genes was used for MR inference following normalization and batch correction. Functional enrichment and survival analyses were conducted to explore prognostic associations. Results: Among 364 TCGA and 492 GEO patients, PGC was associated with more aggressive clinicopathological features and poorer outcomes. We identified 998 DEGs distinguishing PGC and DGC. PGC showed increased FOXM1 (a key regulator of cell proliferation), STAT3, and NF-κB1 activity, while DGC displayed enriched GATA6, CDX2 (a marker of intestinal differentiation), and HNF4A signaling. Functional enrichment highlighted proliferative and inflammatory programs in PGC, and differentiation and metabolic pathways in DGC. MR activity stratified survival outcomes, reinforcing prognostic relevance. Conclusions: PGC and DGC are governed by distinct transcriptional regulators and signaling networks. Our findings provide a biological rationale for location-based stratification and inform targeted therapy development. Full article

Introduction: Low-grade oncocytic tumor (LOT) is a recently described renal neoplasm characterized by indolent clinical behavior, a small nested architecture, and distinctive immunophenotypic features. Its distinction from other eosinophilic renal tumors, such as oncocytoma, eosinophilic chromophobe renal cell carcinoma (E-chRCC), and eosinophilic vacuolated tumor (EVT), can be challenging due to overlapping features. The L1 cell adhesion molecule (L1CAM) is being increasingly recognized as a potential diagnostic marker for LOT. Aims: To evaluate the diagnostic performance of L1CAM in distinguishing LOT from morphologically and immunophenotypically similar eosinophilic renal neoplasms. Methods: A total of 54 eosinophilic renal tumors (10 LOTs, 22 oncocytomas, 18 E-chRCCs, and 4 EVTs) were retrospectively collected from five academic institutions and reclassified according to the 2022 WHO criteria. All cases underwent histopathologic review and immunohistochemical analysis for CK7, CD117, GATA3, cathepsin K, and L1CAM. Results: L1CAM showed strong membranous expression in all LOTs (100%) and was negative in oncocytoma, E-chRCC, and EVT, yielding 100% sensitivity and specificity. Traditional markers exhibited overlapping patterns among tumor types. Conclusions: Our findings confirm L1CAM as a highly sensitive and specific marker for LOT, effectively distinguishing it from other eosinophilic renal neoplasms. Incorporating L1CAM into diagnostic panels may enhance accuracy, particularly in challenging cases. Full article

Human leukocyte extract (HLE), a non-immunogenic dialyzable leukocyte preparation (<10 kDa), may serve as a safe adjuvant in immunotherapy. We investigated the effects of albendazole (ABZ), HLE, and their combination in Mesocestoides vogae infected mice, focusing on lymphoid cells in the peritoneal cavity, the site of larval proliferation and parasite-induced immunosuppression. Peritoneal lymphoid cells were analysed by flow cytometry and qPCR. Cells proliferative responses to ConA, LPS, and parasite excretory/secretory (E/S) antigens, cytokine production (ELISA), IgM and IgG isotypes in exudates and parasite antigen recognition (Western blot) were assessed. Efficacy was measured by larval burden and 14-3-3 gene expression in larvae. HLE combined with ABZ enhanced larval clearance and suppressed 14-3-3 gene expression in larvae. HLE and combination therapy increased CD3⁺ T cell frequencies, especially CD3^+high, reduced regulatory CD3+/IL-10 Tregs and expression of Foxp3⁺. All treatments diminished CD19⁺/IL-10⁺ Bregs, correlating with lower CD9 and Atf3 mRNA levels compared to infected mice. Transcription factors T-bet expression was strongly upregulated, while GATA3 was moderately elevated. IFN-γ production and T/B cell proliferation were restored after HLE and combination therapy, partially, even in the presence of E/S antigens. IgM and total IgG levels against parasite antigens declined, while Th1-associated IgG2a increased in ABZ+HLE and HLE-treated groups. Albendazole failed to reverse the immunosuppressive Treg-type immunity but was more effective in reducing Breg populations and their functions. HLE enhanced ABZ efficacy by restoring Th1 responsiveness, reducing Treg/Breg activity, and modulating antibody profiles. It represents a promising immunomodulatory adjuvant in the treatment of the infections associated with Th2/Treg-driven immunosuppression. Full article

This study aimed to identify genetic variants using a customized next-generation sequencing (NGS) panel for pediatric myelodysplastic syndrome (pMDS) and to explore their associations with cytogenetic and clinical characteristics. Cytogenetic analyses were conducted using G-banding and fluorescence in situ hybridization. NGS was performed with the Ion Torrent Personal Genome Machine for the following genes: GATA2, RUNX1, CEBPA, ANKRD26, ETV6, SAMD9, SAMD9L, PTPN11, NRAS, SETBP1, DDX41, TP53, FLT3, SRP72, and JAK3. Analyses were performed with Ion Reporter 5.20.8.0 software. Genetic variants were classified using the dbSNP, 1000 Genomes, COSMIC, and Varsome databases. We analyzed 25 cases of pMDS; 15 presented abnormal karyotypes, and 19 showed genetic variants. Among the 29 variants identified across 12/15 genes, 27% were pathogenic and 14% were likely pathogenic, with NRAS and GATA2 most frequently associated with disease progression. A new somatic variant of uncertain significance in SETBP1 was detected in seven patients showing heterogeneous clinical outcomes. Genetic variants were found in 7/10 patients with normal karyotypes, indicating that submicroscopic alterations can shed light on disease biology. Our results highlight the critical role of a targeted NGS panel in identifying molecular alterations associated with pMDS pathogenesis, thereby enhancing diagnostic precision, prognosis, and aiding in treatment selection. Full article

Oral cancer, the most common form of head and neck cancer, is worldwide a serious public health problem. Most patients present a locally advanced disease, and face poor prognosis, even with multimodality treatment. They may also develop second primary tumors in the entirety of their upper aerodigestive tract. The most altered signaling pathways are the PI3K/AKT/mTOR, TP53, RB, and the WNT/β-catenin pathways. Genomic and molecular cytogenetic analyses have revealed frequent losses at 3p, 8p, 9p, and 18q, along with gains at 3q, 7p, 8q, and 11q, and several genes frequently affected have been identified, such as TP53, CCND1, CTTN, CDKN2A, EGFR, HRAS, PI3K, ADAM9, MGAM, SIRPB1, and FAT1, among others. Various epigenetic alterations were also found, such as the global hypomethylation and hypermethylation of CDKN2A, APC, MGMT, PTEN, CDH1, TFP12, SOX17, GATA4, ECAD, MGMT, and DAPK. Several microRNAs are upregulated in oral cancer, including miR-21, miR-24, miR-31, miR-184, miR-211, miR-221, and miR-222, while others are downregulated, such as miR-203, miR-100, miR-200, miR-133a, miR-133b, miR-138, and miR-375. The knowledge of this molecular pathogenesis has not yet been translated into clinical practice, apart from the use of cetuximab, an EGFR antibody. Oral tumors are also genetically heterogenous and affect several pathways, which means that, due to the continuous evolution of these genetic alterations, a single biopsy is not sufficient to fully evaluate the most adequate molecular targets when more drugs become available. Liquid biopsies, either resorting to circulating tumor cells, extracellular vesicles or cell-free nucleic acids, have the potential to bypass this problem, and have potential prognostic and staging value. We critically review the current knowledge on the molecular, genetic and epigenetic alterations in oral cancer, as well as the applications and challenges of liquid biopsies in its diagnosis, follow-up, and prognostic stratification. Full article

This study presents the first successful generation and comprehensive characterization of trophoblastic organoids (TOs) and the derivation of three-dimensional cavity- or sac-like structures—termed lacunoids/cystoids—from sheep intracytoplasmic sperm injection (ICSI) embryos. TOs were generated from sheep ICSI embryos for the first time and were shown to express trophoblastic markers at levels comparable to those in embryonic tissue. Detailed morphological characterization was conducted for both the TOs and the derived lacunoids/cystoids. Additionally, the TOs’ interactions with endometrial organoids (EOs), as well as those with preimplantation embryos, were investigated through co-culture experiments. The TOs expressed key trophoblastic markers, including CDX2, GATA3, syncytin-1, KRT18, KRT7, and Sox2, confirming their validity as a model for studying sheep trophoblast biology. The generation of lacunoids/cystoids from the TOs further revealed their structural and developmental characteristics, contributing valuable insights into early placental development and trophoblast-related pathologies. The TOs also supported extended embryonic development, and their co-culture with EOs induced dynamic changes in gene expression, particularly in angiogenesis-related genes, in both organoid types. This novel and reproducible in vitro model offers a reliable platform to study early placental development, effectively recapitulating the biological crosstalk between the trophectoderm and endometrium. The in-depth characterization of TOs and lacunoids/cystoids highlights their potential to advance our understanding of trophoblast differentiation and related developmental disorders. Full article

Background/Objectives: Fish eggs activated with UV-irradiated spermatozoa and exposed to the High Hydrostatic Pressure (HHP) shock to inhibit first cell cleavage develop as gynogenetic Doubled Haploids (DHs) that are fully homozygous individuals. Due to the expression of the recessive genes and side effects of the gamete treatment, survival of fish DHs is rather low, and most of the mitotic gynogenotes die before hatching. Nevertheless, as maternal gene products provided during oogenesis control the initial steps of embryonic development in fish, a maternal effect on the survival of gynogenotes needs to be also considered to affect efficiency of gynogenesis. Thus, the objective of this research was to apply an RNA-seq approach to discriminate transcriptional differences between rainbow trout (Oncorhynchus mykiss) eggs with varied abilities to develop after gynogenetic activation. Methods: Gynogenetic development of rainbow trout was induced in eggs originated from eight females. Maternal RNA was isolated and sequenced using RNA-Seq approach. Survival rates of gynogenotes and transcriptome profiles of eggs from different females were compared. Results: RNA-seq analysis revealed substantial transcriptional differences between eggs originated from different females, and a significant correlation between the ability of the eggs for gynogenesis and their transcriptomic profiles was observed. Genes whose expression was altered in eggs with the increased survival of DHs were mostly associated (GO BP) with the following biological processes: development, cell differentiation, cell migration and protein transport. Some of the genes are involved in the oocyte maturation (RASL11b), apoptosis (CASPASE 6, PGAM5) and early embryogenesis, including maternal to zygotic transition (GATA2). Conclusions: Inter-individual variation of the transcription of maternal genes correlated with the competence of eggs for gynogenesis suggest that at least part of the mortality of the rainbow trout DHs appear before activation of zygotic genome and expression of the lethal recessive traits. Full article

GATA3 is a transcription factor involved in urothelial differentiation and is widely used as a diagnostic marker for urothelial carcinoma (UC). Although loss of GATA3 expression has been linked to more aggressive disease, its prognostic significance remains uncertain. Genetic variation within the GATA3 locus, particularly rs1244159, may influence protein expression and clinical outcomes. We conducted a case control study in Taiwan including 461 UC cases and 586 controls genotyped for four GATA3 SNPs. GATA3 expression was assessed via immunohistochemistry (IHC) in 98 tumor tissues. Logistic regression and Kaplan–Meier analyses were used to evaluate SNP associations and survival outcomes. An XGBoost-based machine learning model with SHAP (SHapley Additive exPlanations) was applied to rank survival predictors. The rs1244159 G allele was associated with a significantly reduced UC risk (adjusted OR = 0.48, p = 0.0231) and higher GATA3 expression (p = 0.0173). High GATA3 expression predicted improved overall survival (p = 0.0092), particularly among G allele carriers (p = 0.0071). SHAP analysis identified age, chemotherapy, and GATA3 expression as the top predictors of survival, consistent with Cox regression results. In conclusion, our integrative analysis suggests that the rs1244159 G allele modulates GATA3 expression and influences UC prognosis. Combining genomics, pathology, and machine learning, GATA3 may serve as a clinically useful biomarker for risk stratification and outcome prediction in UC. Full article

Hearing impairments (HIs) are clinically and genetically very heterogeneous. Finding the causative mutations in patients is frequently a challenge. We investigated two brothers affected by a sensorineural, moderate non-syndromic HI. Exome sequencing revealed that they carried the heterozygous c.812C>T (p.Ser271Leu) variant in GATA3. This gene encodes a transcription factor involved in embryonic development, its mutations causing the autosomal dominant HDR (hypoparathyroidism, deafness, and renal disease) syndrome. The variant affects a conserved residue within the proximal zinc-finger motif of GATA3. Sanger sequencing confirmed the presence of the variant in the two brothers, but it showed that surprisingly it was not carried by any of the parents. Segregation studies on 20 fully informative microsatellite markers in the family confirmed that the variant arose de novo. A benign SNP in the mother, close to the position of the variant, allowed us to determine that this was inherited from the father. Gene reporter functional assays supported the pathogenicity of the variant. Clinical reassessment of the two brothers did not disclose any additional abnormality. We conclude that mosaicism for this de novo mutation in the father’s germ line explains the pattern of inheritance in this family and that p.Ser271Leu is causing this unexpected phenotype of non-syndromic HI. Full article

Polyembryonic maize, capable of producing multiple seedlings from a single kernel, holds great potential value in agricultural and industrial applications, but the seedling quality needs to be improved. In this study, seedlings of two waxy maize (Zea mays L. sinensis Kulesh) inbred lines, D35 (a polyembryonic line with twin shoots) and N6110 (single-shoot), exhibited similar relative growth rates during 1 to 5 days post-germination. UPLC-MS/MS profiling of 3- to 5-day-old seedling roots and shoots revealed that H2JA, MeSAG, and IAA-Val-Me were the common differentially accumulated metabolites (DAMs) of the 3-day-old vs. 5-day-old seedlings of D35 and N6110 in the same tissues, and MeSAG, tZ9G, cZROG, and DHZROG were identified in D35 vs. N6110 across the same tissues and the same periods. RNA-seq analyses showed various processes involved in seedling development, including DNA replication initiation, rhythmic processes, the cell cycle, secondary metabolic processes, and hormone biosynthetic regulation. The differentially expressed genes (DEGs) between D35 and N6110 were significantly enriched in organic hydroxy compound biosynthetic, alcohol biosynthetic, organic hydroxy compound metabolic, abscisic acid biosynthetic, and apocarotenoid biosynthetic processes. The KEGG-enriched pathways of DAMs and DEGs identified that AUX1, AHP, A-ARR, JAR1, SIMKK, ERF1, and GID2 might be conserved genes regulating seedling growth. The integrated analyses revealed that 98 TFs were potentially associated with multiple hormones, and 24 of them were identified to be core genes, including 11 AP2/ERFs, 4 Dofs, 2 bZIPs, 2 MADS-box genes, 2 MYBs, 1 GATA, 1 LOB, and 1 RWP-RK member. This study promotes a valuable understanding of the complex hormone interactions governing twin-shoot seedling growth and offers potential targets for improving crop establishment via seedling quality. Full article

Selenium (Se), as a vital trace element, plays an important role in regulating the antioxidant systems of plants, strengthening photosynthetic capacity, and enhancing their stress resistance. Selenate and selenite are the dominant forms of Se available to plants in soils. This research takes highland barley as the research object, aiming to assess the impacts of plant growth, organic acid metabolite, and six transcription factor families in highland barley seedlings under varying concentrations of Na₂SeO₃. The study indicated that compared to the control group (CK), the plant height of highland barley seedlings under Se1 (0.02 g/kg Na₂SeO₃) treatment significantly increased by 66%. Under the Se2 (0.2 g/kg Na₂SeO₃) treatment, plant height significantly decreased by 28%. With Na₂SeO₃ concentration increased, the pigment content, O₂⁻ production rate, and soluble protein content in highland barley seedlings decreased, while the contents of soluble sugar, MDA, and H₂O₂ increased. Se1 treatment was found to be more beneficial for the growth and development of seedlings. The organic selenium in leaves and roots under Se2 treatment significantly increased by 1105-fold and 188-fold, respectively. The most effective migration capability from soil to leaf under Se1 or Se2 treatment was up to 6.15 or 6.56, respectively. Based on metabolomics, 30 differential metabolites of organic acids were screened from highland barley seedlings under Na₂SeO₃ treatment and showed positive correlationships with organic selenium, inorganic selenium, and total selenium in highland barley seedling leaves. Through transcriptome analysis, heatmap analysis on six major categories of transcription factors (bHLH, MYB, NAC, WRKY, GATA, and HSF) was performed. Under Se2 treatment, approximately two-thirds of the transcription factors showed high expressions. We further screened 26 differentially expressed genes (DEGs) related to Na₂SeO₃ concentration. Based on correlation analysis, there were six genes in the bHLH family, five in MYB, three in NAC, five in WRKY, and three in the GATA and HSF families that showed positive correlations with 30 differential organic acid metabolites. These results enhance our understanding of the relationship between the organic acid metabolites and transcription factor expression in highland barley seedlings under Na₂SeO₃ treatment. Full article

Although the underlying mechanisms are not yet fully understood, vitamin D has been proven to be associated with the pathogenesis of inflammatory bowel disease, participating in immune response and regulating gut microbiota composition. In this study, we established a dextran sodium sulfate-induced colitis model and intervened with vitamin D. Subsequently, colonic histopathology, serum biochemistry, transcription of inflammatory cytokines, gut microbiota, and key signaling pathways were examined. Our research demonstrated that intervention with vitamin D reduced the disease activity index of DSS-induced colitis and improved histopathological changes, protecting tight junction protein ZO-1 and intestinal glands from damage induced by DSS. Analysis of gut microbiota revealed alterations in both α diversity and β diversity in DSS-induced colitis, whereas interventions with active vitamin D corrected the changes in certain bacterial abundance and improved the composition of gut microbiota. The transcription levels of inflammatory cytokines, including IL-23, IL-1β, IFN-γ, IL-6, IL-17, and STING, were elevated in the DSS-induced colitis model. However, intervention with active vitamin D effectively suppressed the transcription of these factors. Finally, immunohistochemistry and Western blotting revealed that the intervention with vitamin D suppressed the expression of proteins associated with the STING pathway, including GATA1, STING, IRF3, and IKBα, leading to inhibition of downstream IFN-β production. Vitamin D administration can ameliorate the severity of DSS-induced colitis by preserving intestinal barrier integrity, modulating gut microbiota composition through suppression of the STING pathway. Full article

Filamentous fungi hold critical industrial value for their ability to produce enzymes, antibiotics, organic acids, and food fermentation. GATA transcription factors (TFs) serve as central regulators of nitrogen metabolism, synthesis of secondary metabolites, stress adaptation, and directly influence fungal development and pathogenicity in filamentous fungi. In this review, we primarily discuss the structural characterization, different types, and phylogenetic analysis of filamentous fungi GATA TFs in filamentous fungi. Subsequently, we systematically summarize the multifunctions of GATA TFs in the mycelial growth, morphological differentiation, and conidial development of filamentous fungi. In addition, we explore their functions in the synthesis of secondary metabolites such as antibiotics (e.g., cephalosporins, penicillins) and organic acids (e.g., ganoderic acid, fumaric acid) in filamentous fungi. Furthermore, we focus on the key roles of GATA TFs AreA and AreB in nitrogen and carbon metabolism in filamentous fungi and their potential synergistic regulatory relationships. Finally, we review the important roles of GATA TFs in the adaptation of filamentous fungi to environmental changes. This review provides research ideas for the development of genetically engineered strains with optimized growth characteristics, increased target metabolites in the fermentation production process, and enhanced environmental adaptability. Full article

The 2024 outbreak of highly pathogenic avian influenza virus (HPAIV) H5N1 in U.S. dairy cattle presented an unprecedented scenario where the virus infected bovine mammary glands and was detected in milk, raising serious concerns for public health and the dairy industry. Unlike previously described subclinical influenza A virus (IAV) infections in cattle, H5N1 infection induced severe clinical symptoms, including respiratory distress, mastitis, and abnormal milk production. To understand the host immune responses and changes, particularly in the mammary gland, we performed single-cell RNA sequencing analysis on bovine milk somatic cells (bMSCs) in vitro exposed to an H5N1 isolate from an infected dairy farm. We identified ten distinct cell clusters and observed a shift toward type-2 immune responses, characterized by T cells expressing IL13 and GATA3, and three different subtypes of epithelial cells based on the expression of genes associated with milk production. Our study revealed temporal dynamics in cytokine expression, with a rapid decline in luminal epithelial cells and an increase in macrophages and dendritic cells, suggesting a role in increased antigen presentation. While viral RNA was detected in bulk-exposed bMSC samples via qRT-PCR, no viral reads were observed in the scRNA-seq data, indicating that the immune responses captured may be due to exposure to viral components rather than productive infection. This research fills a critical gap in understanding the immune responses of bovine mammary glands to H5N1 exposure and highlights the need for further investigation into therapeutic strategies for managing such outbreaks. Full article