Search Results (3,610)

Phytophthora fruit rot caused by Phytophthora capsici is a devastating disease in many solanaceous vegetables, resulting in tremendous yield and economic losses. However, the underlying resistance or susceptibility to P. capsici in eggplant remains obscure. In this study, the transcriptomic analysis was performed between the resistant (G42) and susceptible (EP28) eggplant genotypes at 0, 1, 3 and 5 days post-inoculation (dpi). Taking 0 dpi as the control, a total of 4111, 7496 and 7325 DEGs were expressed at 1, 3 and 5 dpi, respectively, in G42 and 5316, 12675 and 12048 DEGs were identified at 1, 3 and 5 dpi, respectively, in EP28. P. capsici infection induced substantial transcriptional changes in the inoculated fruits. The analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) identified defense-related pathways including ‘plant-pathogen interactions’, ‘mitogen-activated protein kinase (MAPK)’ and ‘hormone biosynthesis and signal transduction’. The hormone-related genes encompassing ethylene, abscisic acid, auxins and gibberellins showed differential expression between G42 and EP28 eggplant genotypes, signifying their important roles in plant disease resistance. P. capsici infection induced the expression of major transcription factors such as MYB, NAC/NAM, bHLH, WRK, HSF, HD-ZIPAP2/ERF and Mad-box. qRT-PCR validation of the selected genes corroborates with RNA-seq, depicting the precision and consistency of the transcriptomic data. According to qRT-PCR and RNA-seq analyses, the expression of the pathogenesis-related gene transcriptional activator, SmPTI6 (Smechr0603020), is upregulated in G42 and downregulated in EP28. This differential expression suggests a potential role in the resistance to P. capsici. Functional analysis via a virus-induced gene silencing (VIGS) system found that silencing SmPTI6 in G42 enhanced infection by P. capsici, indicating that SmPTI6 performs a critical role in response to pathogen attack. The comprehensive results obtained in this study provide a valuable resource for understanding the molecular mechanisms underlying eggplant resistance to P. capsici and for establishing breeding resistant eggplant genotypes to P. capsici. Full article

Buffaloes are a vital genetic resource for dairy production, yet advancements in improving milk production have been somewhat limited. In this study, we performed an integrated analysis of genomic sequencing data from 78 water buffaloes and their milk production traits, with a focus on 305-day milk yield (MY). Leveraging advancements in sequencing technology alongside genome-wide association study (GWAS) methods such as cBLUP, GMATs, and BayesR, we aimed to identify genetic factors that could facilitate the breeding of high-quality buffaloes. Our analysis revealed two significant SNPs associated with milk production traits. Based on these markers, four candidate genes were identified within the surrounding genomic regions. These genes showed significant enrichment in lactation-related pathways, including the prolactin signaling pathway (mitogen-activated protein kinase 10, MAPK10), IL-17 signaling pathway (MAPK10), MAPK signaling pathway (MAPK10), and adipocytokine signaling pathway (MAPK10). The identification of these candidate genes, particularly MAPK10, provides a robust theoretical basis for molecular breeding strategies aimed at enhancing milk production in buffaloes. This work paves the way for more targeted and effective breeding programs in the future. Full article

In exerting its actions on the utilization and storage of nutrients, the hormonal effects of insulin (INS) on target cells include important changes in terms of cell morphology involving cytoskeletal actin. Sensitivity to INS affects intestinal epithelial cells, which express receptors through which tight junctions and barrier permeability are also modulated. Nevertheless, the impact of INS on physiological rather than pathophysiological processes along gastrointestinal epithelia is not fully established. Here, we investigate INS effects on differentiated Caco-2 monolayers challenged by inflammatory stimuli, i.e., interleukin 1 beta (IL-1β) and interferon gamma (IFN-γ), aiming to identify morpho-functional variations potentially associated with INS-dependent responses in intestinal epithelia differentially driven by different inflammation mediators. By observing the actin cytoskeleton, we characterized the impact of INS on actin structures’ organization, both in the absence and presence of pro-inflammatory treatments. Coherently, we observed altered expression of proteins interrelated to cytoskeletal dynamics (FAK, ITGB1), particularly evident in the synergistic action of IFN-γ and INS, also confirmed by the impact on INS-mediated regulation of the MAPK signalling pathway. Overall, the results describe a modular responsiveness of enterocyte-like monolayers to INS, depending on different inflammatory mediators, hinting at the interplay between INS signalling and morpho-functional remodelling in intestinal epithelial cells. Full article

Arteriovenous (AV) access complications remain a major cause of morbidity in hemodialysis patients, influenced by multiple factors, including endothelial inflammation induced by uremia. In this study, we investigated the mechanisms underlying the upregulation of endothelial chemokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) by indolic uremic toxins, as well as their association with AV access complications in hemodialysis patients. In cultured human endothelial cells, IL-8 and MCP-1 were upregulated by indolic uremic toxins through activation of their receptor, the aryl hydrocarbon receptor (AHR), and non-canonical TGF-β pathway involving TAK1/p38 MAPK/AP-1 signaling. In a retrospective observational study of 204 hemodialysis patients, baseline serum IL-8 or MCP-1 were positively correlated with indolic uremic toxins and TGFβ1. Additionally, serum IL-8 ≥ 40.26 pg/mL and serum MCP-1 were independently associated with an increased risk of AV access complications over a 2-year period. In conclusion, we demonstrated that indolic uremic toxins promote endothelial inflammation by inducing IL-8 and MCP-1 expression via AHR activation and non-canonical TGF-β signaling. Clinically, elevated serum IL-8 and MCP-1 were independently associated with an increased risk of AV access complications in hemodialysis patients. Full article

The repeated head impacts experienced by athletes have attracted significant interest from both the public and the scientific community; however, the neurobiological effects following the games are not well understood. For example, a single football match carries the risk of repeated concussive and subconcussive head impacts, which can increase the risk of developing neurodegenerative diseases. Chronic traumatic encephalopathy (CTE) is one of the neurodegenerative conditions athletes often face or are unaware of. However, addressing the disease progression in CTE is difficult to determine due to several reasons, such as the failure to identify risk factors, difficulty in differentiating CTE from other neurodegenerative diseases, and the lack of a specific mechanism by which CTE leads to tau protein accumulation. In addition, CTE symptoms overlap with other neurodegenerative conditions, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), which poses a challenge to producing specific targeted therapy. In this case, ultrasound represents a promising non-invasive technique that enables clear visualization of brain structures and may modulate neuronal activity. The term ultrasound encompasses various modalities; for example, high-intensity focused ultrasound (HIFU) employs thermal energy to ablate cells, whereas low-intensity pulsed ultrasound (LIPUS) delivers mechanical energy that activates molecular signaling pathways to impede the progression of CTE. Therefore, the LIPUS application could potentially minimize the risk of damage in the surrounding tissues of the brain and reduce the disease progression in individuals with CTE. Nevertheless, limited studies have been reported in the literature, with a poor mechanistic approach. Hence, this review aims to highlight the molecular signaling pathways, such as AKT, MAPK, and ERK, affected by LIPUS and emphasize the need for additional research to clarify its mechanistic effects in CTE management. Ultimately, this review aims to contribute to a nuanced understanding of LIPUS as a therapeutic strategy in addressing the complexities of CTE and its associated neurodegenerative disorders. Full article

Background/Objectives: Radiotherapy can cause severe and irreversible brain damage, including cognitive impairment, increased dementia risk, debilitating depression, and other neuropsychiatric disorders. Current radioprotective drugs face limitations, such as single-target inefficacy or manufacturing hurdles. Isoliquiritigenin (ISL), a natural flavonoid derived from licorice root, exhibits broad bioactivities. It exhibits anti-inflammatory, anti-cancer, immunoregulatory, hepatoprotective, and cardioprotective activities. This study aimed to elucidate ISL’s neuronal radiation mitigation effects and key targets. Methods: In vitro and in vivo models of radiation-induced neuronal injury were established. ISL’s bioactivities were evaluated through cellular cytotoxicity assays, LDH release, ROS, ATP, glutamate, and GSH levels. In vivo, ISL’s radiation mitigation effect was evaluated with sucrose preference test, IL-β level, histopathological analysis, and Golgi-Cox staining analysis. Proteomics, pathway enrichment, and ensemble models (four machine learning models, weighted gene co-expression network, protein–protein interaction) identified core targets. Molecular docking and dynamic simulations validated ISL’s binding stability with key targets. Results: ISL attenuated radiation-induced cellular cytotoxicity, reduced LDH/ROS, restored ATP, elevated GSH, and mitigated glutamate accumulation. In rats, ISL alleviated anhedonia-like phenotypes and hippocampal synaptic loss. ISL also significantly suppressed radiation-induced neuroinflammation, as evidenced by reduced levels of the pro-inflammatory cytokine IL-1β. Proteomic analysis revealed that ISL’s main protective pathways included the synaptic vesicle cycle, glutamatergic synapse, MAPK signaling pathway, SNARE interactions in vesicular transport, insulin signaling pathway, and insulin secretion. Grm8, Grik3, and Grin3a were identified as key targets using the integrated models. The expression of these targets was upregulated post-radiation and restored by ISL. Molecular docking and dynamic simulations indicated that ISL showed stable binding to these receptors compared to native ligands. Conclusions: ISL demonstrates multi-scale radiation mitigation activities in vitro and in vivo by modulating synaptic and inflammatory pathways, with glutamate receptors as core targets. This work nominates ISL as an important natural product for mitigating radiotherapy-induced neural damage. Full article

Polystyrene microplastic (MP) and its co-existing contaminants may exert different toxic effects on its surrounding aquatic organisms. In order to detect the intestinal harmful responses, tilapia were subjected to exposure with 75 nm of MPs, 100 ng·L⁻¹ of sulfamethoxazole (SMZ), 5 ng·L⁻¹ of BDE153, and combinations thereof over periods of 2, 4, and 8 days. Enzymatic assays, transcriptomics, proteomics, and metabolomics were employed to evaluate intestinal histopathological effects. Results showed that significant reductions were observed in ATP, ROS, SOD, EROD, lipid metabolism-related enzymes, pro-inflammatory cytokines (TNFα and IL-1β), and apoptosis marker caspase 3 across all groups at day 8. Histological evaluation revealed diminished goblet cell density, with distinct vacuole formation in the BDE153+MPs group. KEGG pathway analysis highlighted disruptions in endocytosis, MAPK signaling, phagosome formation, and actin cytoskeleton regulation. Proteomic findings indicated notable enrichment in endocytosis (decreased sorting nexin-2; increased Si:dkey-13a21.4), MAPK/PPAR signaling, protein processing in the endoplasmic reticulum (Sec61 subunit gamma), and cytoskeletal modulation (reduced fibronectin; elevated activation peptide fragment 1), with or without SMZ and BDE153. Metabolomic profiling showed significant alterations in ABC transporters, aminoacyl-tRNA biosynthesis, protein digestion and absorption, and linoleic acid metabolism. In summary, these findings suggest that BDE153 and MPs synergistically exacerbate intestinal damage and gene/protein expression over time, while SMZ appears to exert an antagonistic, mitigating effect. Full article

Early testicular development is vital for adult male fertility but remains highly vulnerable to stress during the suckling stage. Fermented Chinese chive (Allium tuberosum) is known for its antioxidant and immunomodulatory properties, yet its role in testicular development remains unclear. In this study, Songliao Black piglets received 3‰ fermented Chinese chive (LK group) mixed with starter feed and compared to a control (OD group). Testicular samples at weaning (28 days) underwent transcriptomic and metabolomic analyses. Although no significant differences were observed in gross testicular morphology, the LK group significantly increased individual (13.85%) and litter (15.11%) weaning weights (p < 0.05), with elevated serum triglycerides, total cholesterol, and a 32.2% rise in IgG levels (p < 0.05). Integrated analysis identified 76 shared pathways, including ferroptosis, insulin resistance, PI3K-Akt, MAPK, and cAMP signaling. Upregulated genes in the LK group were mainly related to energy metabolism, antioxidant defense, immune regulation, steroidogenesis, and neuroendocrine signaling, suggesting improved metabolic activity, reduced oxidative stress, and accelerated reproductive maturation. Molecular docking indicated that kaempferol and isorhamnetin from Chinese chive bind strongly to proteins involved in testicular development. Overall, fermented Chinese chive supplementation enhances early testicular development in suckling piglets via integrated modulation of metabolic, immune, and signaling pathways, providing a nutritional strategy to optimize reproductive potential in breeding boars. Full article

Ceramide 1-phosphate (C1P) is a key regulator of cell proliferation and survival in both normal and transformed cells. Major pathways implicated in the mitogenic actions of C1P include activation of the mitogen-activated protein kinases (MAPKs) ERK1-2 and JNK, as well as stimulation of the phosphatidylinositol 3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway, the product of retinoblastoma, or the sphingomyelin synthase (SMS)/diacylglycerol (DAG)/protein kinase C-alpha (PKC-α) pathway. C1P-stimulated cell proliferation can also be mediated through enhanced secretion of vascular endothelial growth factor (VEGF) in macrophages or by releasing lysophosphatidic acid (LPA) in myoblasts. Also, the production of low levels of reactive oxygen species (ROS) can mediate the stimulation of cell growth by C1P, particularly in macrophages. Upregulation of the PI3K/Akt/mTOR pathway is also involved in the inhibition of cell death by C1P, which can also contribute to cell survival by blocking the activity of the ceramide-generating enzymes acid sphingomyelinase (ASMase) and serine palmitoyl transferase (SPT). Moreover, C1P-promoted cell survival involves upregulation of inducible nitric oxide synthase (iNOS) and the subsequent production of nitric oxide (NO). Using photosensitive C1P analogues, it could be concluded that promotion of cell growth and inhibition of cell death were elicited by intracellularly generated C1P in a receptor-independent manner. The aim of the present review is to evaluate in detail the implication of the CerK/C1P axis in controlling cell proliferation and survival in mammalian cells, as well as to discuss and update on the molecular mechanisms by which C1P can accomplish these actions. Full article

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the third leading cause of cancer-related death. Hyperactivation of oncogenes and suppression of tumor suppressor genes/proteins drive HCC initiation and progression. MicroRNAs (miRNAs) critically modulate HCC biology by regulating proliferation, apoptosis, and metastasis. Acting either as tumor suppressors or oncomiRs, they shape core signaling pathways, including PI3K/Akt/mTOR, Hippo–YAP/TAZ, Wnt/β-catenin, RAS/MAPK, and p53. Their dysregulation in tissues and body fluids renders them promising diagnostic biomarkers and therapeutic targets. Preclinical studies demonstrate that miRNA-based strategies—either restoring tumor-suppressive miRNAs (e.g., miR-34a, miR-125a-5p) or inhibiting oncogenic miRNAs (e.g., miR-660-5p)—can suppress HCC progression and reduce treatment resistance. Combination approaches, such as pairing miR-122 mimics with miR-221 inhibitors or delivering miR-326 via nanoparticles, further enhance efficacy by simultaneously targeting multiple oncogenic pathways. This review summarizes recent advances in miRNA-mediated regulation of HCC signaling and highlights their clinical potential, including ongoing trials of miRNA-based diagnostics and therapeutics for early detection, prognostication, and personalized treatment. Full article

Dual-specificity protein phosphatases (DUSPs) are a family of proteins that dephosphorylate both phospho-serine/threonine and phospho-tyrosine residues of Mitogen-Activated Protein Kinases (MAPKs). MAPKs are involved in a large number of cellular processes, including proliferation, differentiation, apoptosis, and stress responses. Therefore, dysregulation or improper functioning of the MAPK signalling is involved in the onset and progression of several diseases, including cancer. Likewise, dysregulation of DUSPs markedly affects cancer biology. The importance of MAPKs in the modulation of tumour development has been known for a long time, and MAPKs are consistently used as molecular targets for cancer therapy. However, in the last decade, DUSPs have acquired a greater interest as possible therapeutic targets to regulate MAPK activity and to prevent resistance mechanisms to MAPK-targeting therapies. Moreover, the possibility of exploiting DUSPs as biomarkers for the diagnosis and prognosis of specific types of cancer is also emerging. In this review, we report what is known in the literature on the role of DUSPs in cancer onset and progression, focusing on those targeting the extracellular signal-regulated kinases (ERKs), in particular ERK1/2 and ERK5 conventional MAPKs. The specific role of each ERK-targeting DUSP in supporting or hampering cancer progression in the context of different types of cancer is also discussed. Full article

The growth of rice (Oryza sativa L.) is affected by long days, which occur throughout the year in southern China, leading to a sharp decline in rice varieties and yields. In order to conduct adaptive genetic breeding research on rice, it is urgent to understand the long days response mechanism of rice. This study used RNA-seq technology to analyze rice under long day conditions and found that RNA, Ehd1, chlorophyll a/b binding protein, were identified as key genes or proteins under long day conditions. MAPK is closely related to long day conditions. This study provides a unique theoretical basis for long-term research and genetic breeding of rice by screening key genes related to the photoperiod. Full article

Background: Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), are critical conditions lacking effective pharmacologic therapies. Lipopolysaccharide (LPS), a bacterial endotoxin, is a well-established trigger of ALI. Emerging evidence suggests that heparin derivatives may attenuate lung injury, but their mechanisms remain unclear. Methods: This study evaluated the protective effects of 2-O, 3-O desulfated heparin (ODSH) in a murine model of LPS-induced ALI. Mice received LPS intratracheally with or without ODSH pre-treatment. Lung injury was assessed by bronchoalveolar lavage fluid (BALF) analysis, Evans blue dye albumin EBDA) extravasation, and histopathology. Results: ODSH treatment significantly reduced BALF protein concentration, inflammatory cell infiltration, and EBDA leakage. ODSH preserved endothelial barrier function in vitro, as evidenced by transendothelial electrical resistance (TER) measurements in human lung microvascular endothelial cell (HLMVEC) monolayers. Histological assessment (H&E staining) and myeloperoxidase (MPO) staining demonstrated reduced lung injury and neutrophil infiltration in the ODSH group. ODSH also downregulated pro-inflammatory mediators (NF-κB, IL-6, p38 MAPK) and upregulated the anti-inflammatory cytokine IL-10. Conclusions: ODSH mitigates LPS-induced ALI by reducing vascular permeability, neutrophilic inflammation, and pro-inflammatory signaling while enhancing IL-10 expression. These findings suggest ODSH may offer a novel therapeutic approach for treating ALI. Full article

Chronic inflammation underpins the pathogenesis of both rheumatoid arthritis (RA) and neurodegenerative conditions such as Alzheimer’s disease (AD). This narrative review explores the role of C-reactive protein (CRP), particularly its monomeric form (mCRP), as a central molecular link connecting systemic autoimmune inflammation with neuroinflammatory and vascular pathology. In RA, fibroblast-like synoviocytes (FLSs) are activated by CRP through CD32/CD64-mediated signaling, triggering proinflammatory cascades involving NF-κB and p38 MAPK. Recent studies have highlighted that locally synthesized CRP within the synovium may convert to mCRP, amplifying inflammation and tissue damage. Beyond RA, mCRP has been identified within amyloid-beta (Aβ) plaques in AD brains, suggesting a direct role in neurodegenerative pathology. Experimental models also demonstrate that mCRP is upregulated in stroke-affected brain regions and associated with complement activation and blood–brain barrier (BBB) disruption, which is central to AD progression. The convergence of pathways involving IL-6, RAGE (receptor for advanced glycation end-products), and mCRP-mediated complement activation reveals a shared axis of inflammation between RA and AD. This highlights the potential of mCRP not only as a biomarker of chronic inflammation but also as a therapeutic target. Furthermore, evidence from periodontal disease and cardiovascular comorbidities highlights the systemic nature of mCRP-driven inflammation, offering insights into the mechanisms of disease overlap. This review advocates for further mechanistic studies into mCRP signaling, particularly its role at the interface of systemic and neuroinflammation, with the goal of identifying new interventional strategies for patients with RA at elevated risk of neurodegenerative and vascular complications. Full article

Alzheimer’s disease (AD) and major depressive disorder (MDD) are prevalent central nervous system (CNS) disorders that share overlapping symptoms but differ in underlying molecular mechanisms. Distinguishing these mechanisms is essential for developing targeted diagnostic and therapeutic strategies. In this study, we integrated multi-tissue transcriptomic datasets from brain and peripheral samples to identify differentially expressed microRNAs (miRNAs) in AD and MDD. Functional enrichment analyses (KEGG, GO) revealed that dysregulated miRNAs in AD were associated with MAPK, PI3K–Akt, Ras, and PD-1/PD-L1 signaling, pathways linked to synaptic plasticity, neuroinflammation, and immune regulation. In contrast, MDD-associated miRNAs showed enrichment in Hippo signaling and ubiquitin-mediated proteolysis, implicating altered neurogenesis and protein homeostasis. Network analysis highlighted key disease- and tissue-specific miRNAs, notably hsa-miR-1202 and hsa-miR-24-3p, with potential roles in neuronal survival and molecular network regulation. These findings suggest that miRNAs may serve as non-invasive biomarkers for diagnosis, prognosis, and treatment monitoring in both disorders. While therapeutic targeting of miRNAs offers promise, challenges such as blood–brain barrier penetration and tissue-specific delivery remain. This integrative approach provides a translational framework for advancing miRNA-based strategies in CNS disease research. Full article