Search Results (6,874)

Background/Objective: Larazotide acetate (LA) is a synthetic octapeptide under development as a therapeutic candidate for celiac disease, acting to reduce intestinal permeability and regulate tight junctions (TJs). Although several studies have shown barrier-protective effects, the cellular mechanisms underlying LA’s actions in the intestinal epithelium remain unclear. This study aimed to elucidate the mechanistic roles of LA in maintaining intestinal epithelial integrity during cellular injury. Methods: C2BBe1 and leaky IPEC-J2 cell monolayers were pretreated with 10 mM LA and subjected to anoxia/reoxygenation (A/R) injury. Transepithelial electrical resistance (TEER), TJ protein localization, and phosphorylation of myosin light chain-2 (MLC-2) were analyzed. In addition, RNA sequencing was conducted to identify differentially expressed genes and signaling pathways affected by LA treatment. Results: LA pretreatment significantly increased TEER and preserved TJ protein organization during A/R injury. Transcriptomic analysis revealed enrichment of genes related to barrier regulation, small GTPase signaling, protein phosphorylation, proliferation, and migration. LA pretreatment markedly reduced MLC-2 phosphorylation, likely through modulation of the ROCK pathway, consistent with RNA-seq findings. Moreover, LA enhanced cellular proliferation, validating transcriptomic predictions. Conclusions: LA exerts a protective effect on intestinal epithelial integrity by stabilizing tight junctions, reducing MLC-2 phosphorylation, and promoting epithelial proliferation. These findings highlight a novel mechanism for LA and support its therapeutic potential in treating gastrointestinal disorders associated with “leaky gut” and mucosal injury. Full article

Background/Objectives: Selenoproteins play indispensable roles in embryonic development, with their dysregulation linked to various metabolic and neurological disorders. This study aims to systematically quantify the mRNA expression levels of all 24 selenoprotein genes in murine heart, brain, liver, and kidney tissues across embryonic (E8.5, E12.5, E18.5) and postnatal (P7, P30, P90) developmental stages, in order to elucidate the regulatory landscape of selenium metabolism during development. Methods: We collected tissues from mice at six developmental stages and performed RNA extraction followed by quantitative real-time PCR (qPCR) to measure the expression of all 24 selenoprotein genes. Data were normalized using the geometric mean of ActB and Gapdh, and statistical analyses were conducted using one-way ANOVA with Duncan’s post hoc test. Results: Our analysis reveals three principal findings: (1) Distinct expression patterns emerge among selenoprotein families—deiodinases (Dio1-3) and thioredoxin reductases (Txnrd1-3) exhibit limited embryonic expression (<20-fold changes), while glutathione peroxidases (Gpx1, Gpx3, Gpx4) and biosynthesis-related genes (Selenop, Msrb1) show substantial postnatal upregulation (up to 600-fold increases); (2) Selenoproteins essential for embryonic survival (Gpx4, Txnrd1, Txnrd2, Selenoi, Selenot) display expression profiles concordant with their essential developmental functions; (3) Selenop and Msrb1, involved in selenium transport and redox regulation, demonstrate early embryonic upregulation with further increases during postnatal development. Conclusions: These spatiotemporal expression patterns elucidate the regulatory landscape of selenium metabolism during development and provide mechanistic insights into the phenotypes associated with selenium deficiency. The findings offer valuable implications for human nutritional interventions and developmental health. Full article

 Background/Objectives: The rapid rollout of 5G has renewed interest in potential reproductive effects of mid-band (3.5 GHz) and millimeter-wave (24 GHz) radiofrequency electromagnetic fields (RF-EMF). We examined frequency- and duration-dependent changes in testicular cytokines, apoptosis-related genes, and sperm quality in rats. Methods: Male Sprague Dawley rats (n = 6 per group) were exposed for 60 days to 3.5 GHz or 24 GHz RF-EMF for 1 h/day or 7 h/day. The sham controls were housed identically. Testicular expressions of IL-10, IL-6, IL-1β, and TNF-α were quantified; Tp53, Bax, Bcl2, and Casp3 mRNA expressions were measured; and sperm concentration, viability, and motility were evaluated. Results: IL-10 was significantly reduced in the 24 GHz group at both 1-h and 7-h exposure duration. At 7 h, TNF-α was also lower at 24 GHz. Casp3 expression was higher and Tp53 was lower at 3.5 GHz at 1-h exposure duration. Sperm concentration and viability were reduced after 24 GHz exposure at 7 h, while sperm motility was reduced after 3.5 GHz exposure at both durations. Conclusions: Exposure to RF-EMF 3.5 GHz primarily impacts sperm motility via extrinsic pro-apoptotic pathways, while exposure to 24 GHz impacts sperm concentration and viability potentially through immune–apoptotic mechanisms, with all negative effects amplified by 7-h daily exposure.  Full article

Plant-parasitic nematodes (PPNs) pose a significant threat to agricultural production and global food security. To mitigate this challenge, quantitative trait locus (QTL) mapping and genome-wide association studies (GWAS) have been extensively employed in crop resistance breeding research. These methods have identified resistance-related genes and genetic markers, offering a solid scientific basis and practical tools for resistance breeding. This review summarizes recent advances in QTL and GWAS applications for enhancing resistance to cyst nematodes (Heterodera glycines, H. filipjevi, and H. avenae), root-knot nematodes (Meloidogyne graminicola and M. incognita), and root-lesion nematodes (Pratylenchus spp.). It also evaluates the commercial deployment of resistance genes, discusses integrated breeding strategies, and highlights future research directions toward developing durable nematode-resistant crops. Full article

Background/Objectives: Obesity, defined by the excessive accumulation of adipose tissue, is associated with an increased risk of type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD). Obesity treatments based on natural products are receiving increasing attention as viable alternatives to conventional treatments. Methods: To investigate the anti-obesity effects of Paliurus ramosissimus leaf extract (PRLE) in vitro and in vivo, we conducted studies using 3T3-L1 pre-adipocytes. The in vivo studies used high-fat diet (HFD)-fed C57BL/6 mice. PRLE effects were assessed through Oil Red O staining, RT-qPCR, Western blot, and morphological analysis of adipose tissue. Results: PRLE significantly reduced lipid accumulation in 3T3-L1 cells without cytotoxicity. PRLE treatment decreased mRNA expression of adipogenic genes (PPARγ, C/EBPα, FABP4, and leptin) and protein levels of adipogenesis-related markers. In HFD-fed mice, PRLE administration significantly reduced body weight gain (p < 0.001), decreased adipose tissue mass, and diminished the weight and size of white adipose tissue. Conclusions: PRLE exhibits anti-obesity effects both in vitro and in vivo, suggesting its potential as a therapeutic agent for obesity prevention. Full article

Type 2 diabetes mellitus (T2DM) is a chronic disease that has become a serious health problem worldwide. Moreover, increased systemic and cerebrovascular inflammation is one of the major pathophysiological features of T2DM, and a growing body of evidence emphasizes T2DM with memory and executive function decline. Bioactive sphingolipids regulate a cell’s survival, inflammatory response, as well as glucose and insulin signaling/metabolism. Moreover, current research on the role of sphingosine kinases (SPHKs) and sphingosine-1-phosphate receptors (S1PRs) in T2DM is not fully understood, and the results obtained often differ. The aim of the present study was to evaluate the effect of metformin (anti-diabetic agent, MET) on the brain’s sphingosine-1-phosphate-related signaling and ultrastructure in diabetic mice. Our results revealed elevated mRNA levels of genes encoding sphingosine kinase 2 (SPHK2) and sphingosine-1-phosphate receptor 3 (S1PR3), which was accompanied by downregulation of sphingosine-1-phosphate receptor 1 (S1PR1) in the hippocampus of diabetic mice. Simultaneously, upregulation of genes encoding pro-inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) was observed. Administration of MET significantly reversed changes in mRNA levels in the hippocampus and reduced Sphk2, Il6, and Tnf, with concomitant upregulation of S1pr1 gene expression. Ultrastructural analysis of diabetic mice hippocampus revealed morphological alterations in neurons, neuropil, and capillaries that were manifested as mitochondria swelling, blurred synaptic structure, and thickened basal membrane of capillaries. The use of MET partially reversed those changes. Our research emphasizes the important role of insulin sensitivity modulation by metformin in the regulation of SPHKs and S1PRs and inflammatory gene expression in a murine model of T2DM. Full article

Butylparaben (BP), a widely used preservative, was implicated in cognitive impairment, though its neurotoxic mechanisms remain elusive. Basal forebrain cholinergic neurons (BFCN) are selectively lost in dementias, contributing to cognitive decline. To explore different mechanisms related with BFCN loss, we employed BF SN56 cholinergic wild-type or silenced cells for Tau, amyloid-beta precursor protein (βApp), acetylcholinesterase (AChE), or glycogen synthase kinase-3 beta (GSK3β) genes, exposing them to BP (0.1–80 µM) for 1 or 14 days alongside triiodothyronine (T3; 15 nM), N-acetylcysteine (NAC; 1 mM), or recombinant heat shock protein 70 (rHSP70; 30 µM). BP disrupted cholinergic transmission by AChE inhibition and provoked cell death through thyroid hormones (THs) pathway disruption, Aβ/p-Tau protein accumulation, AChE-S overexpression, and oxidative stress (OS). Aβ/p-Tau accumulation was correlated with HSP70 downregulation, OS exacerbation, and GSK3β hyperactivation (for p-Tau). BP-induced OS was mediated by reactive oxygen species (ROS) overproduction and nuclear factor erythroid 2-related factor 2 (NRF2) pathway disruption. All observed effects were contingent upon TH signaling impairment. These findings uncover novel mechanistic links between BP exposure and BFCN neurodegeneration, providing a framework for therapeutic strategies. Full article

Rabies, a zoonotic infectious disease causing central nervous system inflammation, remains a threat to public health in regions with limited medical resources. Vaccination effectively reduces rabies incidence and mortality, underscoring the need for vaccines that are cost-effective, immunogenic, protective, and safe. This study constructed a recombinant rabies virus (rRABV)-overexpressing glucocorticoid-induced tumor necrosis factor receptor ligand (GitrL), named rLBNSE-GitrL, using a reverse genetic operating system. rLBNSE-GitrL exhibited similar in vitro phenotypic characteristics and immune safety as the parent RABV (rLBNSE). This recombinant virus stimulated the production of a greater number of activated dendritic cells (DCs) compared to rLBNSE. The enhanced innate immune response induced by rLBNSE-GitrL may be mediated through the activation of innate immune-related signaling pathways, such as the tumor necrosis factor (TNF), and chemokine signaling pathways, and the upregulation of a series of innate immune-related genes, including MMP2, IL-6, CXCL9, TIMP1, IL-17d, and TNF-α. Consequently, rLBNSE-GitrL elicited significantly higher levels of RABV vaccine-induced virus-neutralizing antibodies (VNA), IgG, and IgM compared to rLBNSE as early as 3 days post-immunization (dpi), thereby improving the protective effect in mice. Collectively, the overexpression of GitrL facilitated the induction of early and potent antibody responses following RABV immunization. Full article

Saline-alkali stress seriously affects the growth and development of crops. Sorghum bicolor (L.), a C4 plant, is an important cereal crop in the world, and its growth and geographical distribution are limited by alkali conditions. In this study, sorghum genotypes with different alkaline resistance (alkaline-sensitive Z1 and alkaline-tolerant Z14) were used as experimental materials to explore the effects of alkali on sorghum seedlings. RNA-seq technology was used to examine the differentially expressed genes (DEGs) in alkali-tolerant Z14 to reveal the molecular mechanism of sorghum response to alkali stress. The results showed that plant height, root length, and biomass of both cultivars decreased with time under 80 mM NaHCO₃ treatment, but Z14 showed better water retention abilities. The photosynthetic fluorescence parameters and chlorophyll content also decreased, but the Fv/Fm, ETH, ΦPSII, and chlorophyll content of Z14 were significantly higher than those of Z1. The level of reactive oxygen species (ROS) increased in both sorghum varieties under alkali stress, while the enzyme activities of SOD, POD, CAT, and APX were also significantly increased, especially in Z14, resulting in lower ROS compared with Z1. Transcriptome analysis revealed around 6000 DEGs in Z14 sorghum seedlings under alkali stress, among which 267 DEGs were expressed in all comparison groups. KEGG pathways were enriched in the MAPK signaling pathway, plant hormone signal transduction, and RNA transport. bHLHs, ERFs, NACs, MYBs, and other transcription factor families are actively involved in the response to alkali stress. A large number of genes involved in photosynthesis and the antioxidant system were found to be significantly activated under alkali stress. In the stress signal transduction cascades, Ca²⁺ signal transduction pathway-related genes were activated, about 23 PP2Cs in ABA signaling were upregulated, and multiple MAPK and other kinase-related genes were triggered by alkali stress. These findings will help decipher the response mechanism of sorghum to alkali stress and improve its alkali tolerance. Full article

Mast cells (MCs) belong to the cell network that regulates uterine spiral artery remodeling (uSAR), a critical vascular adaptation supporting placental development and fetal growth. Our previous in vitro study demonstrated that human MCs promote trophoblast invasion, as well as uterine vascular smooth muscle cells (uVSMCs) migration and transition to a synthetic phenotype—essential steps for a successful uSAR. Although MCs are known targets of bisphenol A (BPA), a widespread endocrine-disrupting chemical, its impact on their supportive role in uSAR is unknown. In this study, we used murine cell lines to investigate whether BPA (0.1–100 µM) affects MC-mediated promotion of cellular processes critical for uSAR. Our results showed that BPA exposure hindered MCs’ ability to promote trophoblast invasion and the switch in uVSMCs’ synthetic phenotype and migration. The highest concentrations of BPA altered the expression of genes related to MCs activation and proliferation, and of those involved in trophoblasts invasion. In contrast, low doses induced the expression of pro-inflammatory mediators in MCs without detectable effect on trophoblasts at the transcriptional level. These findings confirmed MCs as key mediators of uSAR, and identified BPA as a disruptor of their function, emphasizing its potential harmful impact on reproductive health. Full article

This study aimed to compare blood samples from Yili horses with outstanding and average performance in 5000 m races through transcriptome sequencing, identify key differentially expressed genes, lncRNAs, and circRNAs, as well as related enriched pathways, and elucidate their regulatory networks. This study used six healthy four-year-old Yili stallions as subjects, divided into an excellent group (E group, n = 3) and an ordinary group (O group, n = 3) based on their 5000-m race performance. Blood RNA-Seq technology was used to analyze differentially expressed mRNAs, lncRNAs, and circRNAs. A total of 2298 mRNAs, 264 lncRNAs, and 215 circRNAs were identified as differentially expressed. Key genes such as EGR1, FOSB, MRPL1, LOC100049811, SIRPB2, and CYTB regulate athletic performance. These genes and their associated RNAs synergistically participate in energy metabolism, protein homeostasis, and muscle remodeling processes, revealing the molecular mechanisms influencing athletic performance and providing important references for identifying candidate genes associated with equine athletic performance. Full article

Pubertal molting represents a pivotal transition in the life cycle of crustaceans, marking the shift from somatic growth to reproductive development. In mud crabs, mating is known to facilitate this process, yet the molecular mechanisms remain poorly understood. Here, we applied full-length transcriptome sequencing to characterize changes in gene expression and alternative splicing (AS) across post-mating ovarian development. AS analysis revealed extensive transcript diversity, predominantly alternative first exon (AF) and alternative 5′ splice site (A5) events, enriched in genes linked to chromatin remodeling, protein regulation, and metabolism, underscoring AS as a fine-tuning mechanism in ovarian development. Comparative analyses revealed profound molecular reprogramming after mating. In the UM vs. M1 comparison, pathways related to serotonin and catecholamine signaling were enriched, suggesting early neuroendocrine regulation. Serotonin likely promoted, while dopamine inhibited, oocyte maturation, indicating a potential “inhibition–activation” switch. In the UM vs. M3 comparison, pathways associated with oxidative phosphorylation, ATP biosynthesis, and lipid metabolism were upregulated, reflecting heightened energy demands during vitellogenesis. ECM-receptor interaction, HIF-1, and IL-17 signaling pathways further pointed to structural remodeling and tissue regulation. Enhanced antioxidant defenses, including upregulation of SOD2, CAT, GPX4, and GSTO1, highlighted the importance of redox homeostasis. Together, these findings provide the first comprehensive view of transcriptional and splicing dynamics underlying post-mating ovarian maturation in Scylla paramamosain, offering novel insights into the molecular basis of crustacean reproduction. Full article

Despite the health concerns regarding alcohol and its link to cancer, moderate consumption of red wine has been associated with healthy aging and longevity, defined as up to one drink per day for women and two drinks per day for men (approximately 142 mL or 5 oz per drink). Previous research has revealed the health benefits of red wine, particularly in relation to cardiovascular disease. However, the influence of genetic factors on these benefits remains to be elucidated. In this study, we explored genes linked to red wine and created a curated gene set that intersects with those related to centenarians, which are markers of exceptional longevity. By analyzing literature from over 190 databases, we identified and validated a curated list of 43 genes associated with red wine and centenarians. We conducted gene set enrichment analysis as well as enrichment analysis of diseases and their tissue distributions. The results suggest that these genes play a crucial role in stress response and apoptosis, which are essential for cell survival and renewal. Additionally, these genes were enriched in pathways associated with smooth muscle cell proliferation, neuroinflammation, nucleotide excision repair, and lipoprotein metabolism (false discovery rate, FDR < 3 × 10⁻⁷). Gene set enrichment analysis indicated significant tissue distribution in the gastrointestinal, cardiovascular, and respiratory systems. Furthermore, the disease–gene enrichment analysis pointed to associations with diseases related to tissues and organs, including cardiovascular disease (heart disease and stroke), type 2 diabetes, gastrointestinal diseases and metabolic diseases, immune diseases, and cancer (FDR < 9.37 × 10⁻⁶); notably, cardiovascular diseases, diabetes, and cancer are leading causes of death, suggesting that these genes may be protective against those diseases. Our review of the literature indicates that individuals who do not currently drink alcohol should not be encouraged to start. However, we propose that moderate consumption of red wine, especially for middle-aged to older adults after 40 years old, can provide significant health benefits due to its components and the positive effects of hormesis. Although further research is necessary to uncover additional genes, this study provides the first genetic overview of the health benefits of red wine, emphasizing its potential in supporting healthy aging and longevity. Full article

Yield components are the most important breeding objectives, directly determining maize high-yield breeding. It is well known that these traits are controlled by a large number of quantitative trait loci (QTL). Therefore, deeply understanding the genetic basis of yield components and identifying key regulatory candidate genes can lay the foundation for maize marker-assisted selection (MAS) breeding. In this study, our aim was to identify the key genomic regions that regulate maize yield component formation through bioinformatic methods. Herein, 554 original QTLs related to 11 yield components, including ear length (EL), hundred-kernel weight (HKW), ear weight (EW), cob weight (CW), ear diameter (ED), cob diameter (CD), kernel row number (KRN), kernel number per row (KNR), kernel length (KL), grain weight per plant (GW), and kernel width (KW) in maize, were collected from the MaizeGDB, national center for biotechnology information (NCBI), and China national knowledge infrastructure (CNKI) databases. The consensus map was then constructed with a total length of 7154.30 cM. Approximately 80.32% of original QTLs were successfully projected on the consensus map, and they were unevenly distributed on the 10 chromosomes (Chr.). Moreover, 44 meta-QTLs (MQTLs) were identified by the meta-analysis. Among them, 39 MQTLs controlled two or more yield components, except for the MQTL4 in Chr. 1, which was associated with HKW; MQTL11 in Chr. 2, which was responsible for EL; MQTL19 in Chr. 3, which was related to KRN; MQTL26 in Chr. 5, which was involved in HKW; and MQTL36 in Chr. 7, which regulated EL. These findings were consistent with the Pearson correlation results, indicating that these traits exhibited co-linked heredity phenomena. Meanwhile, 159 candidate genes were found in all of the above MQTLs intervals, of which, 29 genes encoded E3 ubiquitin protein ligase, which was related with kernel size and weight. Other genes were involved in multiple metabolic processes, including plant hormones signaling transduction, plant growth and development, sucrose–starch synthesis and metabolism, and reproductive growth. Overall, the results will provide reliable genetic resources for high-yield molecular breeding in maize. Full article

Background/Objectives: Neuroblastoma (NB) is an aggressive pediatric malignancy that accounts for nearly 15% of all childhood cancer-related deaths, with high-risk cases showing a poor 20% prognosis and limited response to current therapies. Survivin, encoded by the BIRC5 gene, is an anti-apoptotic protein frequently overexpressed in NB and linked to treatment resistance and unfavorable clinical outcomes. Methods and Results: An analysis of 1235 NB patient datasets revealed a significant association between elevated BIRC5 expression and reduced overall and event-free survival, highlighting survivin as an important therapeutic target in NB. To explore this strategy, we evaluated the efficacy of YM-155, a small-molecule survivin inhibitor, across multiple NB cell lines. YM-155 displayed potent cytotoxic activity in six NB cell lines with IC₅₀ values ranging from 8 to 212 nM and significantly inhibited colony formation and 3D spheroid growth in a dose-dependent manner. Mechanistic analyses revealed that YM-155 downregulated survivin at both mRNA and protein levels, induced apoptosis by about 2–7-fold, and caused G0/G1 phase cell cycle arrest. Moreover, YM-155 treatment enhanced p53 expression, suggesting reactivation of tumor suppressor pathways. Notably, combining YM-155 and the chemotherapeutic agent etoposide resulted in synergistic inhibition of NB growth with ED75 values ranging from 0.17 to 1, compared to either agent alone. In the xenograft mouse model, YM-155 inhibited tumor burden in contrast to controls by about 3-fold, and without any notable toxic effects in vivo. Conclusion: Overall, our findings identify YM-155 as a promising therapeutic agent for high-risk NB by directly targeting survivin and enhancing chemosensitivity. These results support continued preclinical development of survivin inhibitors as part of rational combination strategies in pediatric cancer treatment. Full article