Genes & genomics最新文献

Background: Type 2 diabetes (T2D) is a complex and heterogeneous metabolic disorder that presents significant challenges in treatment development. Emerging evidence indicates that T2D is closely associated with dysregulation of the sphingolipid metabolic pathway, which plays crucial roles in cellular signaling, membrane structure, and metabolic homeostasis.

Objective: To identify and characterize key sphingolipid pathway components that contribute to the pathogenesis of T2D.

Methods: We employed a multi-omics approach integrating genomic, transcriptomic, and metabolomic datasets. Two-sample Mendelian randomization analysis was performed using genome-wide association study data. For functional validation, we conducted in vivo experiments using both lean and ob/ob mice treated with recombinant sphingomyelin phosphodiesterase 1 (SMPD1).

Results: A mouse phenome-liver transcriptome analysis initially identified SMPD1, which converts sphingomyelin to ceramide, as a potential significant factor in T2D. Further investigation using human T2D blood lipid metabolome revealed a decrease of sphingomyelin in T2D patients, strongly suggesting SMPD1's involvement. Two-sample Mendelian randomization, utilizing genome-wide association studies, established a causal effect between SMPD1 gene expression and diabetic traits. Additionally, bulk and single-cell RNA-seq datasets from liver tissues with metabolic dysfunction-associated steatotic liver disease (MASLD) showed that SMPD1 was upregulated in MASLD hepatocytes. Critically, administering recombinant SMPD1 to both lean and ob/ob mice increased hepatic ceramide levels and worsened glucose intolerance and insulin resistance, definitively confirming SMPD1's pathogenic role.

Conclusion: Our findings strongly indicate that SMPD1, as part of the sphingolipid pathway, represents a promising therapeutic target for both T2D and MASLD.

Background: Hybridization within the family Clariidae has been recognized as a crucial strategy for genetic improvement in aquaculture, particularly in Asia and Africa, due to its potential to enhance growth, feed efficiency, tolerance, and disease resistance.

Objective: This review synthesizes information on the biological, genetic, and technological aspects of clariid catfish hybridization, explaining its benefits and highlighting the ecological and regulatory challenges in aquaculture.

Methods: Published information on reproductive biology, hybrid performance, induced breeding, and genomic resources of clariid catfish was examined and summarized.

Results: The reproductive biology of clariid catfish, including external fertilization, overlapping spawning periods, and premating barriers, was described, which shows that viability is promoted. Notable crosses such as Clarias gariepinus × Heterobranchus longifilis and Clarias gariepinus × Clarias macrocephalus were reported, which demonstrated heterosis with higher growth, feed efficiency, and survival rate. Breeding using hormonal agents such as luteinizing hormone-releasing hormone analog, human chorionic gonadotropin, and Ovaprim has facilitated the production of hybrids. Challenges such as partial sterility, phenotypic variability, and decline of vigor in the F₁ generation were identified. Ecological concerns related to hybrid escape, genetic introgression, and biodiversity loss, which pose a risk to native species, were highlighted. The absence of harmonized regulations, limited genomic resources, and insufficient traceability protocols worsens these issues.

Conclusions: Sustainability of clariid catfish hybridization depends on the integration of genomic tools into breeding programs, deployment of sterile hybrids, reinforcement of biosafety systems, and establishment of regional policies. A balance between productivity and conservation is necessary; Clarias hybridization supports aquaculture development but requires careful consideration to protect biodiversity.

Background: Dairy cattle are economically important animal resources contributing to human health and well-being by providing nutritious milk and other products. Non-coding RNAs are involved in biological processes, regulating gene expressions at the levels of messenger. However, the effects on miRNA expression and their function in dairy cattle are still unclear.

Objective: We aimed to understand better miRNA expressions associated with milk and reproduction quantitative trait loci (QTLs) and their locations in dairy cattle.

Methods: In this study, miRNA profiling was performed in blood samples collected from three non-pregnant cows using the Illumina HiSeq 2500 platform. The expression levels of miRNAs were estimated by miRDeep2 and QTLs associated with milk and reproduction were identified using cattleQTLdb. Functional enrichment analysis was performed to determine biological functions or pathways using DAVID.

Results: In total, 406 known and 562 novel expressed miRNAs were identified in three dairy cattle using miRDeep2. A total of 27,652 and 31,064 QTLs associated with milk and reproduction traits were identified by QTL mapping for known and novel miRNAs, respectively. Of these, 1835 and 1020 miRNAs were related to milk and reproduction traits, respectively.

Conclusion: Our study provides a basis for further research to understand the miRNA expressions in dairy cattle and their role in milk and reproduction traits. We suggest that miRNAs may be helpful as biomarkers for improving milk and reproduction traits in dairy cattle through genetic selection.

Background: High-grade serous ovarian cancer (HGSOC) is the most aggressive ovarian cancer subtype, characterized by high recurrence, chemoresistance, and poor prognosis. Although competing endogenous RNA (ceRNA) networks involving long non-coding RNAs (lncRNAs) have been proposed as key regulators of tumor progression, their cell type-specific roles in HGSOC remain unclear.

Objectives: We aimed to identify lncRNA-associated ceRNA networks active within the HGSOC tumor microenvironment.

Methods: We performed an integrative analysis combining single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq datasets. Cancer cells were isolated, and coexpression analyses were conducted using high-dimensional weighted gene coexpression network analysis. The resulting ceRNA modules were validated and functionally annotated using The Cancer Genome Atlas and pathway enrichment analysis.

Results: Our analysis identified a cancer cell-specific ceRNA network involving MIR100HG, mir-224-5p, and EYA4. Interaction prediction and expression correlation analyses indicated that MIR100HG may function as a molecular sponge for mir-224-5p, thereby alleviating its suppression of EYA4. The presence of a 7mer-m8 seed match between mir-224-5p and EYA4 supported this interaction. Pathway analysis suggested a link between the identified ceRNA network and the Wnt signaling pathway, a key driver of tumor initiation and metastasis.

Conclusion: The MIR100HG-mir-224-5p-EYA4 ceRNA network may promote tumor progression by modulating Wnt signaling. These findings offer insights into a potential posttranscriptional regulatory mechanism in tumor development and therapeutic targeting in HGSOC.

Urine-based liquid biopsy represents a transformative, non-invasive diagnostic approach that enables the molecular profiling of tumor-derived biomarkers shed into the urinary tract. By overcoming the limitations of traditional tissue biopsies, this methodology facilitates early cancer detection, real-time monitoring of therapeutic response, and longitudinal disease surveillance. This review provides a comprehensive overview of current urine-based liquid biopsy platforms, with a focus on protein and RNA biomarkers in urological cancers. We highlight the clinical relevance of these biomarkers and discuss technological innovations-including multi-omics integration, machine learning applications, and point-of-care testing-that are expanding their diagnostic utility. By leveraging the unique anatomical accessibility of urological malignancies via urine sampling, this field is poised to significantly enhance precision oncology.