Search Results (32,949)

The rapid development of the nuclear industry and mining has increased environmental radioactive contamination, posing potentially ecological risks and health threats to humans. Uranium compounds are known to exhibit selective nephrotoxicity, but their toxicological processes and mechanisms still remain poorly understood and controversial. In this study, the uranyl-induced toxicity in human renal tubular epithelial cells (HK-2) were explored using flow cytometry, DAPI staining, and comet assays. Our results demonstrate that uranium exposure primarily triggers apoptosis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment and protein–protein interaction (PPI) analyses revealed significant associations with DNA damage. Moreover, aberrant expression of ABC transporters (e.g., ABCB7) and mitochondrial-related proteins confirms uranium-induced mitochondrial dysfunction. Gene Ontology functional annotation implicated extrinsic apoptotic signaling pathways in uranium-induced cell death. The downregulation of the UBL5 protein also pointed to endoplasmic reticulum stress-mediated apoptosis. In summary, uranium exposure can induce the apoptosis of HK-2 cells through intrinsic pathways by damaging DNA and mitochondria and disrupting protein synthesis, with secondary contributions from endoplasmic reticulum stress and extrinsic apoptotic signaling. Full article

Background/Objectives: Previous multi-ethnic genome-wide association studies (GWAS) have identified the GALNT13 rs10196189 polymorphism as a potential genetic marker linked to sprint–power performance. However, its relevance in East Asian populations, particularly the Han Chinese, remains untested. This study aimed to replicate the association of rs10196189 with elite sprint–power athlete status in Han Chinese males and examine its potential influence on physical performance traits and tissue-specific gene regulation. Methods: A total of 188 healthy Han Chinese males (49 elite sprint–power athletes and 139 non-athletic controls) were genotyped using the TaqMan assay. Assessments included strength, sprint, jump, anaerobic power, DXA-derived body composition, and muscle ultrasound. Logistic regression and ROC analyses evaluated the predictive value of rs10196189. Linear regression models adjusted for age and BMI tested genotype–phenotype associations. Tissue expression and functional networks were analyzed using GTEx and HumanBase databases. Results: The G allele frequency was significantly higher in athletes (12.2%) than in controls (5.4%, p = 0.042). Dominant and additive models effectively predicted athlete status (OR = 2.53–2.58, p < 0.05). Although most traits showed no significant associations post-correction, medial gastrocnemius thickness showed a nominal association (β = 0.371, p = 0.011). Functional analyses revealed high GALNT13 expression in brain tissue and co-expression networks enriched in synaptic signaling and glycosylation pathways. Conclusions: This is the first study to validate the association of GALNT13 rs10196189 with elite athletic status in Han Chinese males. Findings provide novel population-specific evidence and propose tissue-specific glycosylation and neural mechanisms as pathways linking this variant to sprint–power phenotypes. Full article

STK26 is highly expressed in colorectal cancer (CRC) and linked to tumorigenesis. Although implicated in unfolded protein response (UPR)-related oxidative stress, whether STK26 regulates CRC occurrence via the ATF6 pathway—a classic UPR branch governing proteostasis and cell survival—remains unestablished. In our research, we found that STK26 expression aberrantly upregulated in CRC is closely associated with poor prognosis. In vitro, tumor phenotype assays showed that STK26 drives CRC cell growth, proliferation, and migration. These effects were reversed by the ATF6 inhibitor Ceapin-A7, demonstrating that STK26’s oncogenic function depends on ATF6. Moreover, transcriptome sequencing revealed that STK26 is associated with the protein folding, sorting, and degradation pathway, and a luciferase reporter assay showed that STK26 activated the ATF6 signal pathway. Furthermore STK26 interacted with p50ATF6 and enhanced its protein stabilization. In vivo studies demonstrated that the administration of the STK26 inhibitor Hesperadin significantly suppressed CRC growth, suggesting a tumor-promoting role for STK26 in CRC pathogenesis. In summary, our research reveals that STK26 is a novel regulator that promotes the growth, proliferation, and migration of CRC cells by activating the ATF6 signaling pathway and stabilizing p50ATF6. Hence, the STK26-ATF6 axis has the potential to become a new target for treating colorectal cancer. Full article

Developmental dysplasia of the hip (DDH) is a congenital disorder influenced by genetic and epigenetic factors. This study aimed to elucidate the molecular pathogenesis of DDH through a comprehensive transcriptomic analysis, identifying differentially expressed genes (DEGs) and long non-coding RNAs (lncRNAs) in hip joint capsules from DDH patients and healthy controls. RNA sequencing data from 12 samples (6 DDH, 6 controls) were retrieved from the NCBI database. Functional annotation was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses via the DAVID tool. A protein–protein interaction (PPI) network of DEGs was constructed using STRING with medium confidence settings. Among 78,930 transcripts, 4.3% were significantly differentially expressed, according to DESeq2 analysis. A total of 3425 DEGs were identified (FDR < 0.05, |log2 FC| > 2), including 1008 upregulated and 2417 downregulated transcripts in DDH samples. Additionally, 1656 lncRNAs were detected among the DEGs. These findings enhance our understanding of the genetic and epigenetic landscape of DDH and highlight the involvement of key biological pathways such as cell cycle regulation and Wnt signaling. This study provides a foundation for future molecular research into the pathogenesis of DDH. Full article

Background: Methamphetamine use, which is disproportionately prevalent among people with HIV, increases risk for cardio- and neurovascular pathology through persistent immune activation and inflammation. Preclinical studies indicate that cannabinoids may reduce markers of pro-inflammatory processes, but data from people with chronic inflammatory conditions are limited. We examined potentially interacting associations of lifetime methamphetamine use disorder (MUD), recent cannabis use, and HIV with four plasma markers of immune and inflammatory functions. Method: Participants with HIV (PWH, n = 86) and without HIV (PWoH, n = 148) provided urine and blood samples and completed neuromedical, psychiatric, and substance use assessments. Generalized linear models examined main and conditional associations of lifetime MUD, past-month cannabis use, and HIV with plasma concentrations of CXCL10/IP-10, CCL2/MCP-1, ICAM-1, and VCAM-1. Results: PWH displayed higher CXCL10/IP-10 than PWoH. Past-month cannabis use was independently associated with lower CXCL10/IP-10 levels and conditionally lower CCL2/MCP-1, ICAM-1, and VCAM-1 levels among people with lifetime MUD, but only PWoH displayed cannabis-associated lower VCAM-1 levels. Conclusions: Human plasma sample evidence suggests that cannabis use is associated with lower levels of immune and inflammatory molecules in the context of MUD or HIV. Cannabinoid pathways may be worthwhile clinical targets for treating sequelae of chronic inflammatory conditions. Full article

Myopia is one of the major public health conditions with significant complications. This study investigates the role of transforming growth factor (TGF)-β2, complement activation, and inflammasome pathways in myopia progression using a Brown Norway rat model. Myopia was induced, and complement regulation was manipulated using gene therapy via adeno-associated virus (AAV) vectors delivering CD55 or CD55 siRNA. Results showed that TGF-β2 exacerbated myopia by upregulating complement components C3 and C5, suppressing CD55, and activating inflammasome pathways through nuclear factor (NF)-κB signaling, leading to axial elongation and increased refractive errors. Overexpression of CD55 via AAV gene therapy effectively counteracted these effects, reducing axial length elongation and inflammation by suppressing inflammasome markers interleukin (IL)-1β and NLR family pyrin domain containing 3 (NLRP3), as confirmed by real-time quantitative PCR and immunofluorescence analyses. Conversely, silencing CD55 intensified TGF-β2-induced effects, further promoting axial elongation and inflammation. These findings highlight the critical role of CD55 in modulating TGF-β2-driven complement and inflammasome activation during myopia progression. The study suggests that gene therapy targeting CD55 could serve as a novel therapeutic strategy to mitigate myopia and related inflammatory processes, offering a promising avenue for managing this significant public health challenge. Full article

N-lactoyl amino acids (Lac-AAs) are key players that regulate appetite and body weight. The most prominent and well-studied member is N-lactoyl phenylalanine (Lac-Phe), which can be induced by food intake, exercise and metformin treatment. However, its broader metabolic impact remains insufficiently characterized. This study investigates the effects of Lac-Phe on insulin signaling, inflammation, and mitochondrial respiration using HepG2 and differentiated C2C12 cell models, as well as isolated rat brain mitochondria and synaptosomes. Our results demonstrate that Lac-Phe significantly impairs insulin-stimulated phosphorylation of key proteins in the insulin signaling pathway, particularly in skeletal muscle cells, indicating disrupted insulin signaling. Additionally, Lac-Phe exposure increases the secretion of pro-inflammatory cytokines in C2C12 skeletal muscle cells and markedly impairs mitochondrial respiration in HepG2 liver cells and rat brain-derived synaptosomes, but not in isolated mitochondria. These findings highlight potential adverse metabolic effects of Lac-Phe, especially when administered at high concentrations, and underscore the necessity of conducting a comprehensive risk assessment and dose optimization before considering Lac-Phe or related Lac-AAs as therapeutic agents. Our work provides important insights into the molecular liabilities associated with Lac-Phe and calls for further studies to balance its therapeutic promise against possible metabolic risks. Full article

The rust disease caused by Melampsora apocyni seriously affects the growth of Poacynum hendersonii. However, the defense mechanisms against rust infection remain unclear. This study explored the regulatory mechanisms of P. hendersonii in response to rust disease through combined physiological, biochemical, and transcriptomic analyses. The results showed that with the increase in disease severity, the chlorophyll content of leaves decreased significantly, while the antioxidant and phenylalanine ammonia lyase activities progressively increased. Mild infection triggered an 11.9-fold surge in salicylic acid levels and a sharp decline in abscisic acid compared to controls, as well as increased synthesis of total phenolics, total flavonoids, chlorogenic acid, cryptochlorogenic acid, isoquercetin, hyperoside, rutin, and astragalin. Transcriptome analysis showed that the “plant–pathogen interaction, plant hormone signal transduction and phenylpropanoid biosynthesis” pathways were significantly up-regulated in the mild infection stage, while “glycerophospholipid metabolism, fatty acid degradation and ABC transporters” were activated in the severe infection stage. In summary, P. hendersonii regulates energy metabolism and phenylpropanoid metabolism through salicylic acid signaling and promotes the accumulation of secondary metabolites and the lignification process of leaves, thereby enhancing rust resistance. Key enzyme genes (COMT, POD, CAD, F5H) and metabolites (chlorogenic acid, isoquercitrin, rutin) can be used as important targets for disease resistance breeding. Our research provides important reference for the prevention and control of M. apocyni in P. hendersonii. Full article

Spinal health depends on the dynamic interplay between mechanical forces, biochemical signaling, and cellular behavior. This review explores how key molecular pathways, including integrin, yeas-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), Piezo, and Wingless/Integrated (Wnt) with β-catenin, actively shape the structural and functional integrity of spinal tissues. These signaling mechanisms respond to physical cues and interact with inflammatory mediators such as interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α), driving changes that lead to disc degeneration, vertebral fractures, spinal cord injury, and ligament failure. New research is emerging that shows scaffold designs that can directly harness these pathways. Further, new stem cell-based therapies have been shown to promote disc regeneration through targeted differentiation and paracrine signaling. Interestingly, many novel bone and ligament scaffolds are modulating anti-inflammatory signals to enhance tissue repair and integration, as well as prevent scaffold degradation. Neural scaffolds are also arising. These mimic spinal biomechanics and activate Piezo signaling to guide axonal growth and restore motor function. Scientists have begun combining these biological platforms with brain–computer interface technology to restore movement and sensory feedback in patients with severe spinal damage. Although this technology is not fully clinically ready, this field is advancing rapidly. As implantable technology can now mimic physiological processes, molecular signaling, biomechanical design, and neurotechnology opens new possibilities for restoring spinal function and improving the quality of life for individuals with spinal disorders. Full article

This study investigated the effects of dietary supplementation with varying levels (CK: 0.0 g/kg; RL: 0.1 g/kg; RM: 1.0 g/kg; RH: 10.0 g/kg) of Rhodotorula mucilaginosa on muscle composition, serum biochemical indicators, antioxidant capacity, lipid metabolism, and the mTOR signaling pathway in red claw crayfish (Cherax quadricarinatus). Results showed that, compared to CK, treatment groups had higher muscle crude protein, fat, leucine, histidine, arginine, and essential amino acids (p < 0.05), and lower saturated fatty acids (p < 0.05). Treatment groups also exhibited increased activities of alkaline phosphatase, acid phosphatase, superoxide dismutase, catalase, glutathione S-transferase, lysozyme, albumin, total protein, and antioxidant capacity (p < 0.05), with reduced activities of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and triglycerides (p < 0.05). In the hepatopancreas, treatment groups showed significant downregulation of AMP-activated protein kinase α, β, and γ, and carnitine palmitoyltransferase 1 genes (p < 0.05). Conversely, genes involved in lipid anabolism (peroxisome proliferator-activated receptor γ, acetyl-CoA carboxylase, fatty acid synthase, sterol regulatory element-binding protein, protein kinase B, and mammalian target of rapamycin 1 and 2) were upregulated (p < 0.05). In conclusion, R. mucilaginosa supplementation affects muscle composition, lipid metabolism, and mTOR signaling. The optimal dose is 1.0 g/kg. Full article

Stem cell therapies, including mesenchymal (MSCs) and haematopoietic stem cells (HSCs), have shown promise in neurodegenerative diseases. Here, we investigated the therapeutic effects of a defined combination of unmanipulated MSCs and CD34⁺ HSCs, termed Neuro-Cells (NC), in a murine model of Alzheimer’s disease (AD), the APPswe/PS1dE9 mouse. At 12 months of age, mice received intracisternal injections of NC (1.39 × 10⁶ MSCs + 5 × 10⁵ HSCs) or vehicle. After 45 days, behavioural testing, immunohistochemical analyses of amyloid plaque density (APD), and cortical gene expression profiling were conducted. NC-treated APP/PS1 mice exhibited preserved object recognition memory and reduced anxiety-like behaviours, contrasting with deficits observed in untreated transgenic controls. Histologically, NC treatment significantly reduced the density of small amyloid plaques (<50 μm²) in the hippocampus and thalamus, and total plaque burden in the thalamus. Gene expression analysis revealed that NC treatment normalised or reversed disease-associated changes in insulin receptor (IR) signalling and neurotrophic pathways. Specifically, NC increased expression of Bdnf, Irs2, and Pgc-1α, while attenuating aberrant upregulation of Insr, Igf1r, and markers of ageing and AD-related pathology (Sirt1, Gdf15, Arc, Egr1, Cldn5). These findings indicate that NC therapy mitigates behavioural and molecular hallmarks of AD, potentially via restoration of BDNF and insulin receptor-mediated signalling. Full article

Background/Objectives: Eupatorium lindleyanum DC (Eup), a traditional Chinese medicinal herb, is widely used for treating inflammation-mediated diseases, including pneumonia. However, its potential therapeutic effects on inflammation-driven liver fibrosis remain to be elucidated. This study aimed to investigate the effects of Eup on carbon tetrachloride (CCl₄)-induced liver fibrosis and elucidate its underlying mechanisms. Methods: The chemical constituents of Eup were analyzed using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-LC/MS). A CCl₄-induced liver fibrosis murine model and LX-2 cells were used in study. Serum biochemical assays, histological analysis, qRT-PCR, ELISA, and Western blot were used to assess Eup’s anti-inflammatory and anti-fibrotic properties. RNA sequencing (RNA-seq) was employed to identify potential mechanisms, with validation by Western blot. Results: 89 and 49 compounds were identified in Eup under positive and negative ion modes, respectively. In vivo, Eup treatment decreased collagen deposition and expression levels of fibrosis-related genes, including collagen I and α-smooth muscle actin. Additionally, Eup alleviated hepatic inflammation. In vitro, Eup inhibited FBS-induced hepatic stellate cell (HSCs) activation. Gene set enrichment analysis (GSEA) indicated that Eup significantly downregulated the platelet-derived growth factor (PDGF)/platelet-derived growth factor receptor-beta (PDGFR-β) signaling pathway, which was further validated in both CCl₄-induced fibrotic livers and PDGF-BB-activated HSCs using western blot. Conclusions: Eup attenuated liver fibrosis by inhibiting inflammation and suppressing HSCs activation via downregulating PDGF/PDGFR-β signaling pathway. Full article

Drought stress significantly limits crop growth and yield, and the mechanisms underlying genotypic variation in drought tolerance remain unclear. This study investigated the growth and transcriptomic responses of two sorghum varieties, drought-sensitive Jinza 35 (V1) and drought-tolerant Longza 24 (V2), under drought conditions. Comparative transcriptomic analysis, along with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, revealed distinct molecular mechanisms between the two varieties. Both varieties exhibited drought-responsive changes in photosynthesis-related pathways. However, the drought-tolerant V2 showed significant enrichment in phenylpropanoid biosynthesis, starch-sucrose metabolism, and plant hormone signaling pathways, suggesting enhanced metabolic flexibility under stress. In contrast, V1 primarily activated ribosome metabolism and cell cycle regulation pathways, indicating a less adaptive response focused on basic cellular processes. These findings highlight key metabolic and regulatory differences underlying drought tolerance in sorghum. The study provides valuable molecular insights and candidate pathways for future functional studies and the breeding of drought-resistant sorghum varieties. Full article

Neurodegeneration is increasingly recognized not as a linear trajectory of protein accumulation, but as a multidimensional collapse of biological organization—spanning intracellular signaling, transcriptional identity, proteostatic integrity, organelle communication, and network-level computation. This review intends to synthesize emerging frameworks that reposition neurodegenerative diseases (ND) as progressive breakdowns of interpretive cellular logic, rather than mere terminal consequences of protein aggregation or synaptic attrition. The discussion aims to provide a detailed mapping of how critical signaling pathways—including PI3K–AKT–mTOR, MAPK, Wnt/β-catenin, and integrated stress response cascades—undergo spatial and temporal disintegration. Special attention is directed toward the roles of RNA-binding proteins (e.g., TDP-43, FUS, ELAVL2), m6A epitranscriptomic modifiers (METTL3, YTHDF1, IGF2BP1), and non-canonical post-translational modifications (SUMOylation, crotonylation) in disrupting translation fidelity, proteostasis, and subcellular targeting. At the organelle level, the review seeks to highlight how the failure of ribosome-associated quality control (RQC), autophagosome–lysosome fusion machinery (STX17, SNAP29), and mitochondrial import/export systems (TIM/TOM complexes) generates cumulative stress and impairs neuronal triage. These dysfunctions are compounded by mitochondrial protease overload (LONP1, CLPP), UPR maladaptation, and phase-transitioned stress granules that sequester nucleocytoplasmic transport proteins and ribosomal subunits, especially in ALS and FTD contexts. Synaptic disassembly is treated not only as a downstream event, but as an early tipping point, driven by impaired PSD scaffolding, aberrant endosomal recycling (Rab5, Rab11), complement-mediated pruning (C1q/C3–CR3 axis), and excitatory–inhibitory imbalance linked to parvalbumin interneuron decay. Using insights from single-cell and spatial transcriptomics, the review illustrates how regional vulnerability to proteostatic and metabolic stress converges with signaling noise to produce entropic attractor collapse within core networks such as the DMN, SN, and FPCN. By framing neurodegeneration as an active loss of cellular and network “meaning-making”—a collapse of coordinated signal interpretation, triage prioritization, and adaptive response—the review aims to support a more integrative conceptual model. In this context, therapeutic direction may shift from damage containment toward restoring high-dimensional neuronal agency, via strategies that include the following elements: reprogrammable proteome-targeting agents (e.g., PROTACs), engineered autophagy adaptors, CRISPR-based BDNF enhancers, mitochondrial gatekeeping stabilizers, and glial-exosome neuroengineering. This synthesis intends to offer a translational scaffold for viewing neurodegeneration as not only a disorder of accumulation but as a systems-level failure of cellular reasoning—a perspective that may inform future efforts in resilience-based intervention and precision neurorestoration. Full article

The Kazakh horse, one of China’s indigenous primitive breeds, is renowned for its remarkable adaptability and distinctive physiological traits. The ovary is a vital reproductive organ in female animals, responsible for oocyte production and hormone secretion. However, limited research has been conducted on gene expression profiles in the ovarian tissue of equine species. To address this gap, the present study performed transcriptomic sequencing on ovarian tissues from 12 Kazakh horses in different physiological states. A total of 979 differentially expressed mRNAs were identified, including 619 upregulated and 360 downregulated genes. Among these, key genes such as COL1A1, LHCGR, KISS1, NTRK2, COL1A2, and THBS4 were identified as differentially expressed. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that 374 of these genes were primarily involved in ovarian steroidogenesis, the PI3K-Akt signaling pathway, and ECM-receptor interactions among 292 enriched pathways. This study provides a comprehensive transcriptomic profile of equine ovarian tissue, offering in-depth insights into differential gene expression and signal pathways associated with ovarian development in Kazakh horses, providing theoretical foundations and referential data for future research in equine ovarian development and reproductive studies. Full article