Search Results (89)

Background: The function and mechanism of N6-methyladenosine (m6A) methylation in pressure-overload cardiac fibrosis remains limited and unclear. This study aims to analyze and predict m6A modifications present in mouse hearts because of transverse aortic constriction (TAC). Materials and Methods: Twelve male C57BL/6 mice were randomly assigned to two groups, TAC group and sham group. The RNA Dot Blot assay was employed to evaluate the overall m6A methylation levels in both TAC and sham mice. The expression level of m6A-related enzymes were investigated through RT-PCR and Western blotting. MeRIP-seq and RNA-seq analyses were conducted to identify differentially modified m6A genes and mRNA expression genes. The protein–protein interaction (PPI) network was carried out to choose potential hub genes. Additionally, the transcription factor (TF)–microRNA (miRNA) coregulatory network and the drug–hub gene interaction network were built based on these hub genes. Furthermore, molecular docking simulations were also performed to analyze the interactions between drugs and hub genes. Results: Compared with the sham group, the TAC group demonstrated elevated levels of global m6A methylation. METTL3 and METTL14 were significantly upregulated, whereas FTO and ALKBH5 were significantly downregulated following TAC. MeRIP-seq analysis identified 17,806 m6A peaks associated with 9184 genes and 16,392 m6A peaks associated with 8550 genes in the TAC and sham groups, respectively. In conjunction with RNA-seq data, 66 genes were identified as exhibiting concurrent differences in both m6A methylation levels and mRNA expression. Six hub genes, Cd33, Irf4, Nr4a2, Hspa1b, Nr4a1, and Adcy1, were identified through the construction of a PPI network. The TF-miRNA coregulatory network contains six hub genes, 31 miRNAs, and 24 TFs. The drug–hub genes interaction network included five hub genes and 36 candidate drugs. Conclusions: The m6A modification is prevalent in TAC-induced cardiac fibrosis and significantly contributes to the fibrotic process by regulating critical genes. In the future, it may emerge as one of the potential cardiac fibrosis therapeutic targets. Full article

Specialized herbivores like giant pandas (Ailuropoda melanoleuca), red pandas (Ailurus fulgens), and bamboo rats, which primarily consume bamboo, are at risk of nutrient deficiencies, particularly vitamin B12 (VB12), potentially leading to cardiovascular diseases. This study explored the effects of VB12 supplementation on cardiovascular health in silver star bamboo rats (Rhizomys pruinosus). We first conducted a comprehensive genome annotation of R. pruinosus, laying the foundation for in-depth evolutionary studies. Comparative transcriptomic analysis revealed that genes related to cardiovascular disease (e.g., Sgcb, Adcy2, Itga1, Itgb8, Ifng, and Gpc1) were upregulated in the livers of R. pruinosus compared to carnivorous and omnivorous rodents, indicating a higher cardiovascular disease risk. After 60 days of VB12 supplementation, liver transcriptome analysis revealed significant improvements in cardiovascular health markers, including reduced cholesterol synthesis and enhanced fatty acid metabolism. Serum biochemical assays indicated that VB12 supplementation led to reduced homocysteine levels, decreased low-density lipoprotein (LDL)-to-high-density lipoprotein (HDL) ratios, and increased the apolipoprotein A-to-apolipoprotein B ratio. These findings suggest that VB12 may mitigate cardiovascular disease risk and could be considered in the dietary management of specialized bamboo-eating species. Our study provides valuable insights into disease prevention strategies for these species with similar dietary habits. Full article

Fish reproduction requires suitable salinity and temperature, as well as sufficient energy. This study investigated temperature and salinity effects on ovarian development of Lateolabrax maculatus and energy metabolism differences between reproduction and growth. Two salinities (4‰ and 30‰) and temperatures (18 ± 1 °C and 30 ± 1 °C) formed four treatments: SWNT (30‰, 30 ± 1 °C), SWLT (30‰, 18 ± 1 °C), FWLT (4‰, 18 ± 1 °C), and FWNT (4‰, 30 ± 1 °C). GSI and sex hormones (FSH, LH, E2, and 17α,20β-DHP) were measured. Transcriptome analysis explored how temperature and salinity regulate ovarian development in L. maculatus, while integrated transcriptomic and targeted energy metabolomic analyses revealed energy metabolism differences between ovary and muscle during this process. The results showed that low salinity (4‰) and low temperature (18 ± 1 °C) synergistically promoted ovarian development in the FWLT group, as indicated by a significant increase in GSI and elevated levels of key sex hormones (FSH, LH, E2, and 17α,20β-DHP). Transcriptome analysis showed that low temperature activated pathways involved in steroidogenesis, oocyte maturation, and meiosis, and genes such as ADCY6, PRKACB, CPEB4, FZD7-A, and CCND2 were significantly upregulated. Salinity changes mainly affected amino acid metabolism, cholesterol metabolism, and the insulin signaling pathway. Genes such as PCSK9 and CKM may regulate ovarian development by regulating hormone synthesis and energy metabolism. Comprehensive transcriptome and metabolome analyses show that glycolysis is downregulated and oxidative phosphorylation is upregulated in the ovary, suggesting that ovarian oogenesis tends to be energized by aerobic metabolism. The TCA cycle may be used more for providing biosynthetic precursors and facilitating the transport of substrates between the mitochondrion and the cytoplasm rather than just as a source of ATP. Muscle tissue relies primarily on glycolysis for rapid energy production and may redistribute energy to the gonads, prioritizing the energy needs of the ovaries and contributing to the dynamic balance between reproduction and growth. This study provides insights into the molecular mechanisms of how environmental factors regulate fish reproduction, providing a theoretical basis and potential molecular targets for the regulation of reproduction and optimization of aquaculture environments. Full article

Background: Paroxysmal dyskinesias (PDs) are rare, episodic movement disorders characterized by sudden and involuntary hyperkinetic motor events. In paediatric populations, their diagnosis is often complicated by clinical overlap with epilepsy and other neurological conditions. Genetic underpinnings have increasingly been recognized as key to understanding phenotypic heterogeneity and guiding treatment. Objectives: This systematic review aims to provide a comprehensive overview of paediatric PD, with a focus on genetic aetiologies, clinical features, subtype classification, and therapeutic approaches, including genotype–treatment correlations. Methods: We systematically reviewed the literature from 2014 to 2025 using PubMed. Inclusion criteria targeted paediatric patients (aged 0–18 years) with documented paroxysmal hyperkinetic movements and genetically confirmed or clinically suggestive PD. Data were extracted regarding demographics, dyskinesia subtypes, age at onset, genetic findings, and treatment efficacy. Gene categories were classified as PD-specific or pleiotropic based on functional and clinical features. Results: We included 112 studies encompassing 605 paediatric patients. The most common subtype was Paroxistic Kinesigenic Dyskinesia (PKD). Male sex was more frequently reported. The mean onset age was 5.99 years. A genetic diagnosis was confirmed in 505 patients (83.5%), involving 38 different genes. Among these, PRRT2 was the most frequently implicated gene, followed by SLC2A1 and ADCY5. Chromosomal abnormalities affecting the 16p11.2 region were identified in ten patients, including deletions and duplications. Among the 504 patients with confirmed monogenic variants, 390 (77.4%) had mutations in PD-specific genes, while 122 (24.2%) carried pleiotropic variants. Antiseizure drugs—particularly sodium channel blockers such as carbamazepine and oxcarbazepine—were the most frequently reported treatment, with complete efficacy documented in 59.7% of the studies describing their use. Conclusions: Paediatric PDs exhibit significant clinical and genetic heterogeneity. While PRRT2 remains the most common genetic aetiology, emerging pleiotropic genes highlight the need for comprehensive diagnostic strategies. Sodium channel blockers are effective in a subset of genetically defined PD, particularly PRRT2-positive cases. Patients with pathogenic variants in other genes, such as ADCY5 and SLC2A1, may benefit from specific therapies that can potentially change their clinical course and prognosis. These findings support genotype-driven management approaches and underscore the importance of genetic testing in paediatric movement disorders. Full article

Meat quality is influenced by genetic, nutritional, and microbial factors, with increasing attention on the role of gut-derived metabolites. In this study, we conducted untargeted metabolomics of 10 gut tract sites and RNA sequencing (RNA-seq) of longissimus dorsi muscles in Meigu goats and Liangshan black sheep raised under standardized conditions. Results showed that goat muscle contained significantly higher levels of essential amino acids (e.g., methionine) and specific fatty acids (e.g., C18:3_N6, C20:4_N6), suggesting improved nutritional quality. Transcriptomic analysis identified 3133 differentially expressed genes (DEGs), among which ADCY1 and SLC38A4 were upregulated in goats and strongly associated with meat traits. Using integrative correlation analysis, we uncovered 17 genes and 19 gut metabolites that were significantly correlated with more than eight meat quality parameters across multiple gut sites. Notably, these metabolites included bioactive compounds such as L-tyrosine ethyl ester and pelargonidin 3-O-glucoside, while genes were enriched in pathways related to amino acid transport, cAMP signaling, and muscle development. Together, these findings highlight a potential gut–muscle axis involving metabolite-mediated modulation of muscle gene expression, contributing to breed-specific differences in meat composition and quality. This study provides a valuable framework for improving ruminant meat quality through integrative multi-omics analysis. Full article

Cannabis vaping, particularly involving cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), rapidly delivers highly concentrated cannabinoids to the brain, potentially affecting the hippocampus. This study examined differential expression of long noncoding RNAs (lncRNAs) and mRNAs in the hippocampus after acute exposure to vaporized CBD or THC. Male ICR mice were exposed to vaporized CBD or THC (50 mg, n = 5/group), and hippocampal tissues were collected at 1, 3, and 14 days post-exposure. Total RNA sequencing was conducted on day 1 samples, and selected transcripts were validated using qRT-PCR across multiple time points. CBD led to significant up- or downregulation of L3mbtl1, Wnt7a, and Camk2b at day 1. However, Wnt7a showed gradual recovery at days 3 and 14. In the THC group, Grin2a, Gria3, and Golga2 were significantly upregulated, while Drd1, Drd2, Gnal, and Adcy5 were significantly downregulated at day 1. Time-course analysis showed that Drd2 expression returned to baseline by day 14, whereas Adcy5 remained persistently downregulated through days 3 and 14. In the CBD group, NONMMUT069014.2 was upregulated, while NONMMUT033147.2 and NONMMUT072606.2 were downregulated at day 1; notably, NONMMUT072606.2 showed a transient increase at day 3 before returning to baseline. In the THC group, NONMMUT085523.1 and NONMMUT123548.1 were upregulated, whereas NONMMUT019734.2, NONMMUT057101.2, and NONMMUT004928.2 were downregulated, with most showing gradual recovery by day 14. Correlation analysis revealed that THC-responsive lncRNAs—including NONMMUT004928.2, NONMMUT057101.2, and NONMMUT019734.2—were strongly associated with downregulated mRNAs such as Drd2 and Adcy5. These findings highlight cannabinoid-specific hippocampal transcriptomic responses and suggest potential regulatory roles for lncRNA–mRNA interactions in cannabinoid-induced neural changes. Full article

Basal cell carcinoma (BCC), the most common skin cancer, is primarily driven by Hedgehog (Hh) and TP53 pathway alterations. Although additional pathways were implicated, the mutational landscape in Asian populations, particularly Koreans, remains underexplored. We performed whole-exome sequencing of BCC tumor tissues from Korean patients and analyzed mutations in 11 established BCC driver genes (PTCH1, SMO, GLI1, TP53, CSMD1/2, NOTCH1/2, ITIH2, DPP10, and STEAP4). Mutational profiles were compared with Caucasian cohort profiles to identify ethnicity-specific variants. Ultraviolet (UV)-exposed and non-UV-exposed tumor sites were compared; genes unique to non-UV-exposed tumors were further analyzed with protein–protein interaction analysis. BCCs in Koreans exhibited distinct features, including fewer truncating and more intronic variants compared to Caucasians. Korean-specific mutations in SMO, PTCH1, TP53, and NOTCH2 overlapped with oncogenic gain-of-function/loss-of-function (GOF/LOF) variants annotated in OncoKB, with some occurring at hotspot sites. BCCs in non-exposed areas showed recurrent mutations in CSMD1, PTCH1, and NOTCH1, suggesting a UV-independent mechanism. Novel mutations in TAS1R2 and ADCY10 were exclusive to non-exposed BCCs, with protein–protein interaction analysis linking them to TP53 and NOTCH2. We found unique ethnic-specific and UV-independent mutational profiles of BCCs in Koreans. TAS1R2 and ADCY10 may contribute to tumorigenesis of BCC in non-exposed areas, supporting the need for population-specific precision oncology. Full article

Approximately 70% of people will experience a traumatic event in their lifetime, but post-traumatic stress disorder (PTSD) will only develop in 3.9% and complex post-traumatic stress disorder (CPTSD) in 1–8% of the population worldwide, although in some countries (e.g., Poland and Northern Ireland) it will develop in a much higher percentage. Stress-related disorders have a complex pathogenesis involving neurophysiological, genetic, epigenetic, neuroendocrine and environmental factors. This article reviews the current state of knowledge on the molecular aspects of selected PTSD symptoms: hypervigilance, re-experiencing, emotion dysregulation and dissociation, i.e., the symptoms with strong neurobiological components. Among analysed susceptibility factors are specific gene polymorphisms (e.g., FKBP5, COMT, CHRNA5, CRHR1, 5-HTTLPR, ADCY8 and DRD2) and their interactions with the environment, changes in the HPA axis, adrenergic hyperactivity and disturbances in the activity of selected anatomical structures (including the amygdala, prefrontal cortex, corpus callosum, anterior cingulate gyrus and hippocampus). It is worth noting that therapeutic methods with proven effectiveness in PTSD (TF-CBT and EMDR) have a substantial neurobiological rationale. Molecular aspects seem crucial when searching for effective screening/diagnostic methods and new potential therapeutic options. Full article

We profiled the gene expressions in the hypothalamic paraventricular nuclei of 12 male and 12 female pups from a standard rat model of infantile spasms to determine the sex dichotomy of the neurotransmission genomic fabrics. Infantile spasms were triggered in rat pups prenatally primed with two doses of betamethasone followed by the postnatal repeated administration of N-methyl-D-aspartic acid to induce spasms. Publicly available microarray data were used to characterize each gene in each condition for both sexes by the independent transcriptomic features: average expression level, control of the transcript abundance, and expression correlation with every other gene. This study revealed substantial sex differences in the expression level, control, and inter-coordination of the investigated genes among the studied groups. The transcriptomic differences assist in providing a molecular explanation of the behavioral differences and development of infantile epilepsy spasm syndrome in the two sexes. Full article

Differences in skin and hair phenotypes between the scapular and ventral regions of yaks (Bos grunniens) are obvious and become more prominent with age. However, the genetic mechanism that causes differences in yak skin at different ages has not been reported. In this study, we investigated the transcriptomic profile of yak skin across different ages (0.5 years, 2.5 years, and 4.5 years) and body sites (scapular and ventral regions). Differential gene expression analysis was initially conducted to explore the transcriptomic differences in skin at different ages and different body sites. Subsequently, weighted gene co-expression network analysis (WGCNA) was employed to analyze the transcriptomic data comprehensively. The results showed that, among all comparison groups, the Y2.5_S vs. Y2.5_V group (regional comparison) exhibited the highest number of DEGs, with 491 genes (179 upregulated and 312 downregulated), followed by the Y2.5_V vs. Y0.5_V group (age comparison), which had 370 DEGs (103 upregulated and 267 downregulated). DEGs such as IGF2BP3, ADCY8, FOSL1, and S100A8 were found in all comparison groups of different ages, and multiple members of the HOX gene family including HOXC10, HOXA9, HOXA6, HOXB9, and HOXB6 were differentially expressed in comparison groups at different sites. Functional enrichment analysis showed that there were more obvious differences in immune function between different ages of skin and more obvious differences in endocrine function between different parts of skin. WGCNA revealed that genes related with immunity such as GLYATL2, ACSL5, and SPDEF were the core genes of the co-expression module associated with the scapula region, and multiple genes related to hair follicle development such as FOXN1, OVOL1, DLX3, HOXC13, and TCHH were found to be the hub genes of the co-expression module associated with the ventral region. Overall, our study provides valuable insights into the transcriptomic complexity of yak skin across different ages and body sites. The differential gene expression patterns and co-expression network modules identified in this study lay the foundation for further research on skin biology and adaptation mechanisms in yaks. Full article

The genetic mechanisms underlying the formation of defects, such as bumps and growths on the hock joints in pigs, remain poorly understood. Therefore, the aim of this study was to investigate the relationship between runs of homozygosity (ROH) and the formation of hock joint bumps, with the goal of identifying associated SNPs and candidate genes involved in these defects. The study was conducted on a population of Large White breed pigs (n = 568) using runs of homozygosity (ROH) analysis and genome-wide association studies (GWAS). The results suggested that the predisposition to hock joint bumps in pigs may have arisen due to recent selective breeding pressure. Using GWAS, 27 SNPs were identified at the suggestive significance level, with one SNP (rs325478346) reaching genome-wide significance. These markers are localized in genes associated with various biological processes, including lipid metabolism (VIPR2 and CFTR), inflammatory processes (MTURN and ADCY2), connective tissue structural integrity (COL27A1), muscle regeneration (PAMR1), and ion exchange and cellular homeostasis (KCNIP4 and NALCN), as well as regulation of cell growth, extracellular matrix remodeling, and fibroblast differentiation (CEP120 and SCUBE3). Further research utilizing omics technologies will provide deeper insights into the pathogenesis of hock joint bumps and contribute to the development of strategies for the prevention and potential treatment of this defect. Full article

Cadmium (Cd) contamination in plants and soil poses significant risks to livestock, particularly sheep. Cd exposure often leads to severe gastrointestinal diseases in sheep that are difficult to treat. Milk-derived exosomes, particularly those from sheep milk (SM-Exo), have shown potential in treating gastrointestinal disorders, though their efficacy in Cd-induced colitis remains unclear. In this study, we investigated the therapeutic potential of SM-Exo in a Cd-induced colitis model. Hu sheep were exposed to Cd, and their fecal microbiota were collected to prepare bacterial solutions for fecal microbiota transplantation (FMT) in mice. The changes in gut microbiota and gene expression were analyzed through microbiome and transcriptomics. Our results showed that prior to treatment, harmful bacteria (e.g., Bacteroides and Parabacteroides) were increased in FMT mice. SM-Exo treatment increased beneficial bacteria, particularly Lachnoclostridium, and activated the Cyclic Adenosine Monophosphate (cAMP) pathway, upregulating genes like Adcy1, Adcy3, CREB, and Sst. These changes were linked to reduced Cd-induced cell death and alleviation of colonic inflammation. In conclusion, SM-Exo appears to be a promising treatment for Cd-induced colitis, likely through modulation of the gut microbiota and activation of the cAMP pathway. Full article

Background: Ionizing radiation (IR) exposure poses a significant health risk due to its widespread use in medical diagnostics and therapeutic applications, necessitating rapid and effective biomarkers for assessment. Objective: The aim of this study is to identify the serum proteomic signature of IR exposure in patients undergoing radiotherapy (RT). Methods: Blood samples were obtained from eighteen patients with head and neck cancer (HNC) and five patients with rectal cancer before and immediately after they underwent curative intensity-modulated radiotherapy (IMRT). The comprehensive serum proteome was analyzed in individual samples using nanoHPLC-MS/MS. Results: Forty radiation-modulated proteins (RMPs), 24 upregulated and 16 downregulated, with a fold change ≥1.5 and p-value < 0.05 were identified. About 40% of the RMPs are involved in acute phase response, DNA repair, and inflammation; the key RMPs were ADCY1, HGF, MCEMP1, CHD4, RECQL5, MSH6, and ZNF224. Conclusions: This study identifies a panel of serum proteins that may reflect the radiation response, providing a valuable molecular fingerprint of IR exposure and paving the way for the development of sensitive and specific biomarkers for early detection and clinical management of IR-related injuries. Full article

Follicle development in dairy goats is lower after induced estrus during the non-breeding season, reducing conception rates and challenging year-round milk supply. This study investigated follicle development during the breeding and non-breeding seasons and explored molecular mechanisms for variations in the proportions of follicles of different sizes using ovarian RNA-seq and in vitro experiments. Induced estrus during the non-breeding season used a simulated breeding season short photoperiod and male effect methods, while the male effect method was used during the breeding season. This study identified an increase in follicle size during the breeding season and performed RNA-seq on ovaries to explore the underlying causes. The RNA-seq analysis elucidated pathways associated with cellular and hormonal metabolism and identified adenylyl cyclase 5 (ADCY5) as a key differentially expressed gene. In vitro experiments demonstrated that interfering with ADCY5 in ovarian granulosa cells (GCs) reduced steroid synthesis. Conversely, the overexpression of ADCY5 increased steroid synthesis. ADCY5 affects the biological function of GCs and consequently influences follicle development through the cAMP-response element binding protein (CREB) and p38 mitogen-activated protein kinase phosphorylation (MAPK) pathways. Overall, our findings demonstrate that follicle development in dairy goats differs between the breeding and non-breeding seasons and that the differential expression levels of the ADCY5 gene contribute to this discrepancy. Full article

In livestock production, deeply understanding the molecular mechanisms of growth and metabolic differences in different breeds of cattle is of great significance for optimizing breeding strategies, improving meat quality, and promoting sustainable development. This study aims to comprehensively reveal the molecular-level differences between Chinese domestic cattle and Simmental crossbred cattle through multi-omics analysis, and further provide a theoretical basis for the efficient development of the beef cattle industry. The domestic cattle in China are a unique genetic breed resource. They have characteristics like small size, strong adaptability, and distinctive meat quality. There are significant differences in the growth rate and meat production between these domestic cattle and Simmental hybrid cattle. However, the specific molecular-level differences between them are still unclear. This study conducted a comprehensive comparison between the domestic cattle in China and Simmental crossbred cattle, focusing on microbiology, short-chain fatty acids, blood metabolome, and transcriptome. The results revealed notable differences in the microbial Simpson index between the domestic and Simmental crossbred cattle. The differential strain Akkermansia was found to be highly negatively correlated with the differential short-chain fatty acid isocaproic acid, suggesting that Akkermansia may play a key role in the differences observed in isocaproic acid levels or phenotypes. Furthermore, the transcriptional metabolomics analysis indicated that the differentially expressed genes and metabolites were co-enriched in pathways related to insulin secretion, thyroid hormone synthesis, bile secretion, aldosterone synthesis and secretion, and Cyclic Adenosine Monophosphate (cAMP) signaling pathways. Key genes such as ADCY8 and 1-oleoyl-sn-glycero-3-phosphocholine emerged as crucial regulators of growth and metabolism in beef cattle. Full article