Search Results (4,714)

Conventional plant disease management primarily depends on chemical pesticides. However, with the rising concerns related to human health, environmental sustainability, and the emergence of resistant pathogens, biocontrol agents (BCAs) have gained more attention as eco-friendly alternatives. Among the potential biocontrol agents, yeasts stand out due to their safety, adaptability, and diverse antagonistic mechanisms, ranging from competition and enzyme secretion to volatile compound production and immunity induction. Despite their potential, yeast-based BCAs face limitations in field efficacy, regulation, and an incomplete understanding of their molecular interactions. Most current studies focus on simple, pairwise interactions, overlooking the complexity of agroecosystems, where plants, pathogens, and BCAs interact within broader microbial communities. This review addresses the importance of understanding tripartite interactions among plants, pathogens, and yeasts, supported by integrated transcriptomic and comparative genomic approaches, as well as meticulous observations of phenotypic expressions to uncover strain-specific defense mechanisms and mode of action. By referring to well-studied models like Blumeria graminis f.sp. hordei–Hordeum vulgare–Pseudozyma flocculosa and Trichoderma tripartite systems, we highlight the underexplored potential of yeasts to modulate plant immunity and influence pathogen behavior through complex molecular crosstalk. Bridging these knowledge gaps through integrating proteomic, metabolomic, and transcriptomic analyses, we can better harness yeasts in sustainable and targeted biocontrol strategies. Full article

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins play evolutionarily conserved roles in intracellular vesicle trafficking and membrane fusion across eukaryotes. In pathogenic fungi, various SNARE homologs have been shown to critically regulate host infection processes. Here, we characterize the functional roles of CfSec22 in the sweet potato black rot pathogen Ceratocystis fimbriata. Phylogenetic and domain analyses demonstrate that CfSec22 shares homology with Sec22 proteins from Saccharomyces cerevisiae (ScSec22), Magnaporthe oryzae (MoSec22), and other fungi, containing both the characteristic Longin homology domain and V-SNARE domain. Functional studies reveal that CfSec22 regulates growth, conidiation, and virulence of C. fimbriata. Deletion of CfSEC22 resulted in abnormal vacuole morphology and impaired endocytosis. The ΔCfsec22 mutant displayed heightened sensitivity to diverse stress conditions: oxidative, endoplasmic reticulum, and cell wall stressors. Subcellular localization studies confirmed the endoplasmic reticulum residence of CfSec22. Finally, we established that CfSec22 regulates the secretion of virulence-associated proteins and is required for the induction of ipomeamarone in infected sweet potato tissues. Together, our findings demonstrate that CfSec22-mediated vesicle trafficking serves as a critical regulatory mechanism supporting growth, conidiogenesis, and pathogenicity in C. fimbriata. Full article

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen frequently associated with delayed wound healing, particularly in chronic skin injuries. Its capability to form biofilms, secrete virulence factors, and the faculty to compete with other microorganisms makes it a major challenge in clinical wound management. Recent literature reveals different molecular and cellular mechanisms through which P. aeruginosa disrupts the wound healing process. Findings highlight that it interferes with key phases of healing by modulating host immune responses, degrading extracellular matrix components, and inhibiting keratinocyte migration. Its quorum-sensing systems regulate the expression of critical virulence factors such as exotoxin A, elastases, pyocyanin, and rhamnolipids. Additionally, the production of the biofilm matrix components alginate, and polysaccharides provide protection against host defenses and antibiotics. Interactions with other microorganisms, including antagonistic effects on Staphylococcus epidermidis and synergistic relationships with Staphylococcus aureus, modify the wound microbiota. Promising therapeutic alternatives have shown efficacy in disrupting biofilms and reducing virulence. These insights remark the importance of targeting both P. aeruginosa and its ecological interactions to enhance wound healing outcomes and develop more effective treatments. This review aimed to highlight the pathogenic role of P. aeruginosa and its interactions with other microbial species in the context of skin wound healing. Full article

Increased hepatic triacylglycerol (TG) storage in lipid droplets (LDs) is a hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). Human carboxylesterase 1 (CES1) regulates TG storage and secretion in hepatocytes, but the mechanism remains to be elucidated. We performed studies in rat hepatoma McArdle RH7777 cells stably transfected with CES1 cDNA and in Ces1d-deficient mice using a variety of biochemical, pharmacological and cell biology approaches including the assessment of gene expression, confocal immunofluorescence microscopy, lipid synthesis measurements and quantitative mass spectrometry. CES1-expressing cells accrued more TG compared to cells lacking CES1 when incubated with oleic acid. CES1 increased the expression of Srebf1c, Nr1h3 and Nr1h2 encoding transcription factors (SREBP1c and LXRα and LXRβ, respectively) that regulate the expression of lipogenic genes. Additionally, CES1 increased the expression of Acsl1 encoding an enzyme catalyzing fatty acid activation and the expression of Dgat1 and Dgat2 encoding enzymes catalyzing TG synthesis. Treatment of CES1-expressing cells with PPARγ antagonist (GW9662), LXR antagonist (GSK2033) or CYP27A1 inhibitor Felodipine prevented CES1-mediated fatty acid esterification into TG. Ces1d-deficient mice fed high-fat diet (HFD) presented with decreased expression of Nr1h3, Nr1h2, Srebf1c and reduced hepatic TG content. Felodipine and GSK2033 treatment eliminated the differential effects on TG concentration between wild-type and Ces1d-deficient hepatocytes. The results suggest that CES1/Ces1d activates PPARγ, LXR and SREBP1c pathways, thereby increasing TG synthesis and LD storage by augmenting fatty acid esterification. Full article

Fracture repair complications occur in 5–10% of cases, despite bone’s regenerative capacity. Bone marrow-derived (BM) stem cells have been extensively investigated for orthopedic applications but, given the critical role that periosteum plays in fracture repair, periosteal-derived (PO) cells offer a promising alternative cell source. This study compared the in vitro osteogenic capacities of equine BM and PO cells. Passage 3 cells from each source were maintained in osteogenic medium for up to 10 days. Osteogenesis was assessed by Runx2, Osterix, and alkaline phosphatase (ALP) mRNA up-regulation, induction of ALP activity, and matrix mineralization. Comparisons were made by paired t tests, repeated measures one-way or two-way ANOVAs, as indicated. BM cells proved superior to PO cells in osteogenesis assays. BM cells significantly up-regulated Runx2, Osterix, and ALP mRNAs, ALP activity, and secreted a mineralized matrix by day 10. PO cells did not. BMP-2 expression increased significantly in BM cells in osteogenic medium, whereas BMP-2 expression in PO cells was unchanged. Exogenous BMP-2 did not restore osteogenesis in periosteal cells, indicating that ex vivo expansion affects periosteal osteogenic capacity beyond BMP-2 downregulation. Clinical applications of PO cells will require the identification and exogenous provision of requisite stimulatory factors and substrates. Full article

The lung is increasingly recognized as an organ with dual endocrine and respiratory roles, participating in a complex bidirectional crosstalk with systemic hormones and local/paracrine activity. Endocrine and paracrine pathways regulate lung development, ventilation, immunity, and repair, while pulmonary cells express hormone receptors and secrete mediators with both local and systemic effects, defining the concept of the “endocrine lung”. This narrative review summarizes current evidence on the endocrine–pulmonary axis. Thyroid hormones, glucocorticoids, sex steroids, and metabolic hormones (e.g., insulin, leptin, adiponectin) critically influence alveologenesis, surfactant production, ventilatory drive, airway mechanics, and immune responses. Conversely, the lung produces mediators such as serotonin, calcitonin gene-related peptide, endothelin-1, leptin, and keratinocyte growth factor, which regulate vascular tone, alveolar homeostasis, and immune modulation. We also describe the respiratory manifestations of major endocrine diseases, including obstructive sleep apnea and lung volume alterations in acromegaly, immunosuppression and myopathy in Cushing’s syndrome, hypoventilation in hypothyroidism, restrictive “diabetic lung”, and obesity-related phenotypes. In parallel, chronic pulmonary diseases such as chronic obstructive pulmonary disease, interstitial lung disease, and sleep apnea profoundly affect endocrine axes, promoting insulin resistance, hypogonadism, GH/IGF-1 suppression, and bone metabolism alterations. Pulmonary neuroendocrine tumors further highlight the interface, frequently presenting with paraneoplastic endocrine syndromes. Finally, therapeutic interactions are discussed, including the risks of hypothalamic–pituitary–adrenal axis suppression with inhaled corticosteroids, immunotherapy-induced endocrinopathies, and inhaled insulin. Future perspectives emphasize mapping pulmonary hormone networks, endocrine phenotyping of chronic respiratory diseases, and developing hormone-based interventions. Full article

Acute lung injury (ALI) is a severe pulmonary disorder characterized by the disruption of the alveolar–capillary barrier, leading to impaired oxygenation and pulmonary edema. Current pharmacological interventions primarily involve the use of steroid drugs, oxygen radical scavengers, and bronchodilators. However, the therapeutic efficacy of these interventions remains inconsistent. Canthin-6-ones, a class of tryptophan-derived alkaloids, exhibit anti-inflammatory, antioxidant, and immunomodulatory properties. In this study, we synthesized a novel Canthin-6-one derivative, namely HCX3, and evaluated its potential beneficial effects and underlying mechanisms on ALI. Prior to the experimental study, network pharmacology analysis revealed that HCX3 may exert anti-inflammatory effects in the context of ALI through the regulation of multiple signaling pathways, including the NF-κB pathways. To validate these findings, Lipopolysaccharide (LPS) was employed to stimulate RAW 264.7 macrophages and bone marrow-derived macrophages (BMDMs) to construct cellular models of inflammatory response associated with ALI. Our data demonstrated that exposure to HCX3 significantly inhibited the transcription and the secretion of multiple pro-inflammatory mediators, including IL-1β, IL-6, and TNF-α, in a dose-dependent manner. Additionally, HCX3 reduced LPS-induced phosphorylation levels of p65 and IκB-α in macrophages, indicating an inhibitory effect of the compound on the activation of NF-κB signaling pathway. Collectively, our data suggest that HCX3 exhibits significant anti-inflammatory effects by inhibiting NF-κB-related signaling pathways, providing new insights for ALI treatment. Full article

Background/Objectives: The interaction between brain-metastasizing melanoma cells and surrounding microglia shapes the immune tumor microenvironment and influences tumor progression. Gene expression analysis revealed that sphingosine-1-phosphate receptor 1 (S1PR1), encoding the S1P1 receptor, is upregulated in microglia upon interaction with melanoma cells. Here, we investigated the functions of S1P1 in microglia and its contribution to melanoma–microglia crosstalk. Methods: We examined the effects of S1P1 inhibition on microglia and four brain-metastasizing human melanoma cell lines in monocultures and co-cultures using the selective S1P1 antagonist NIBR0213 and S1PR1 gene knockdown. Results: We found that melanoma-secreted IL-6 upregulated S1PR1 expression in microglia. S1P1 inhibition increased expression of CD32, CD150, and CD163 in microglia; however, CD150 and CD163 upregulation was abolished in the presence of melanoma cells. S1P1 inhibition downregulated immunosuppressive and anti-inflammatory factors in microglia, including CD274, SOCS3, TGFBR1, TGFBR2, and JunB, promoting a pro-inflammatory phenotype. It also reduced viability of both melanoma and microglia cells, inducing apoptosis in melanoma-associated microglia, possibly via downregulation of CH25H, an upstream regulator of SREBPs. In co-cultures, melanoma cells were more sensitive than microglia to NIBR0213-induced growth arrest. In 3D spheroid cultures, NIBR0213 delayed melanoma–microglia aggregation. Combined treatment with the BRAF inhibitor Vemurafenib and NIBR0213 enhanced Vemurafenib efficacy in three of four melanoma lines. Conclusions: S1P1 contributes to the immunosuppressive phenotype of microglia. Inhibiting the S1P/S1P1 axis impairs viability and crosstalk between melanoma cells and tumor-activated microglia, offering a potential therapeutic strategy for melanoma brain metastases. Full article

Serpulids are among the few annelid groups capable of building skeletal structures by secreting calcium carbonate. Compared with other biomineralizing organisms, their control over tube construction is relatively limited, making them vulnerable to environmental changes. To distinguish between intrinsic biological regulation and extrinsic environmental influence in tube formation, we examine the calcareous tube of Hydroides elegans, focusing on the tube ultrastructure, mineral composition, elemental distribution, organic-inorganic constituents, and biomineralization mechanism. The results show that the tube consists of three superimposed layers: an innermost organic sheet, an intermediate lamello-fibrillar calcite layer, and an outermost spherulitic prismatic calcite layer. The outer spherulitic prismatic layer frequently exhibits bioerosion, trapped sedimentary particles, and fan-shaped aragonite aggregates, indicating pronounced environmental influence. In contrast, the middle lamello-fibrillar calcite fabric is highly organized and closely integrated with the innermost organic sheet, indicating strictly biological controls. This study highlights the combined effect of biological controls and environmental influences in serpulid tube calcification, contributing to our understanding of their adaptive evolution in changing oceans. Full article

Introduction: The Hedgehog (Hh) signaling pathway is aberrantly activated in various types of cancer and plays a critical regulatory role. However, its biological significance in gastric cancer remains unclear. In this study, the mechanism underlying the role of Hh in gastric cancer progression and prognosis was investigated through bioinformatics analysis as well as in vitro and in vivo experiments. Methods: In this study, a systematic analysis of scRNA-seq datasets and bulk RNA-seq datasets from gastric cancer patients derived from the GEO database and TCGA database was performed by us, which revealed the activation characteristics of Hh in different cell types within the gastric cancer tumor microenvironment (TME). Furthermore, through conducting multiplex immunofluorescence staining experiments on clinical gastric cancer samples, we clarified the association mechanism between fibroblasts with highly activated Hh and the gastric cancer tumor immunosuppressive microenvironment. Finally, by means of in vitro and in vivo experiments, we elucidated the key molecular mechanism by which fibroblasts with highly activated Hh remodel the gastric cancer tumor immunosuppressive microenvironment. Results: We identified a distinct subpopulation of fibroblasts, designated MMP1 + FIB, in the gastric cancer tumor microenvironment. Studies revealed that this subpopulation can significantly activate Hh, suggesting it may play a crucial role in the regulation of the TME. Subsequent mechanistic investigations further confirmed that MMP1 + FIB exhibits a significant correlation with the immunosuppressive state of the TME (R = 0.29, p = 2.5 × 10^−0.8). In terms of the specific functions, the complement system in this fibroblast subpopulation is significantly activated (p < 0.05); further studies demonstrated that MMP1 + FIB can induce the polarization of macrophages toward the M2 subtype (an immunosuppressive phenotype) by specifically secreting complement C3 protein. Collectively, these processes contribute to the establishment of an immunosuppressive TME and ultimately promote the proliferation and metastasis of gastric cancer cells. Discussion: Aberrant activation of the Hh signaling pathway promotes gastric cancer progression via the MMP1 + FIB–C3–macrophage axis, providing a potential therapeutic strategy for targeting the tumor microenvironment. Full article

Metabolic syndrome (MetS), characterized by obesity, insulin resistance, dyslipidemia, and hypertension, is a growing global health concern. This review examines the relationship between adipose tissue insulin resistance (AT-IR) and MetS. Adipose tissue functions beyond energy storage as an endocrine organ that regulates metabolism through hormone and cytokine secretion. When adipose tissue becomes insulin resistant, it contributes to systemic metabolic dysfunction through impaired glucose uptake and dysregulated adipokine production. This creates a bidirectional relationship where AT-IR promotes MetS development, while MetS-associated inflammation further worsens adipose insulin sensitivity. Key mechanisms include inflammatory signaling, altered adipokine profile, and mitochondrial dysfunction. Understanding these interactions offers therapeutic opportunities, as targeting adipose tissue function may provide novel approaches for MetS treatment. This review synthesizes current evidence on AT-IR-MetS interactions and discusses therapeutic implications and future research directions. Full article

Prostate stem cell antigen (PSCA) is a Ly6/uPAR protein that targets neuronal nicotinic acetylcholine receptors (nAChRs). It exists in membrane-tethered and soluble forms, with the latter upregulated in Alzheimer’s disease. We hypothesize that PSCA may be linked to a wider spectrum of neurological diseases and could induce neuroinflammation. Indeed, PSCA expression is significantly upregulated in the brain of patients with multiple sclerosis, Huntington’s disease, Down syndrome, bipolar disorder, and HIV-associated dementia. To investigate PSCA’s structure, pharmacology, and inflammatory function, we produced a correctly folded water-soluble recombinant analog (ws-PSCA). In primary hippocampal neurons and astrocytes, ws-PSCA differently regulates secretion of inflammatory factors and adhesion molecules and induces pro-inflammatory responses by increasing TNFβ secretion. Heteronuclear NMR and ¹⁵N relaxation measurements reveal a classical β-structural three-finger fold with conformationally disordered loops II and III. Positive charge clustering on the molecular surface suggests the functional importance of ionic interactions by these loops. Electrophysiological studies in Xenopus oocytes point on ws-PSCA inhibition of α3β2-, high-, and low-sensitive variants of α4β2- (IC₅₀ ~50, 27, and 15 μM, respectively) but not α4β4-nAChRs, suggesting targeting of the β2 subunit. Ensemble docking and molecular dynamics simulations predict PSCA binding to high-sensitive α4β2-nAChR at α4/β2 and β2/β2 interfaces. Complexes are stabilized by ionic and hydrogen bonds between PSCA’s loops II and III and the primary and complementary receptor subunits, including glycosyl groups. This study gives new structural and functional insights into PSCA’s interaction with molecular targets and provides clues to understand its role in the brain function and mental disorders. Full article

300 healthy Chinese perch (Siniperca chuatsi) (34.35 ± 0.47 g) were randomly divided into five groups (P1–P5) fed diets supplemented with 0, 0.2, 0.4, 0.8, and 1.6 g/kg protease for 8 weeks. Compared to P1, protease supplementation significantly up-regulated endogenous pepsinogen genes (pga1 and pgc) and down-regulated the muscle deamination gene ampd. In comparison to P1, the expression level of the hepatic gene ast increased in P2, P3, and P5, while gdh elevated in P2 and P3 (p < 0.05). Compared to P1, the expression of feeding-related gene npy decreased while pomc increased in P2; agrp increased in P3; and pomc and cart decreased in P5, resulting in significant increases in feed intake in P2, P3, and P5 (p < 0.05). Glycolytic genes (gk and pk) and lipid metabolism gene pparα were up-regulated in P2, P3 and P5, while hsl increased in P3 but decreased in P5 (p < 0.05). P5 exhibited significantly improved weight gain rate, specific growth rate, protein efficiency ratio, and protein retention rate, alongside reduced feed conversion ratio compared with P1. Therefore, dietary 1.6 g/kg protease significantly enhances growth, improves feed efficiency, stimulates pepsinogen secretion, and modulates deamination, glycolytic, and lipid metabolism genes in Siniperca chuatsi. Full article

Introduction: Tumor- and/or treatment-associated hypothalamic damage results in reduced quality of life and increased morbidity due to sleep disorders in survivors of craniopharyngioma. Methods: The narrative review is based on a search of Web of Science, MEDLINE/PubMed, and Embase databases for the identification of publications. The search terms craniopharyngioma, sleep disorders, fatigue, and daytime sleepiness were used. Selected English language papers published 1970–2025 were included. Results: Circadian rhythms (wakefulness and sleep) are controlled by hypothalamic suprachiasmatic nuclei and regulated by melatonin. A dysregulation of circadian rhythms due to altered melatonin secretion can be observed in craniopharyngioma with hypothalamic involvement. Furthermore, sleep quality is regulated by lateral hypothalamic areas, the ventrolateral preoptic nucleus, and monoaminergic nuclei which function as the arousal system. Flexible changes between sleep and wakefulness can be achieved through interaction of arousal and sleep-promoting systems named “flip–flop” switch. Insomnia can be the result of damage to the ventrolateral preoptic nucleus. Excessive daytime sleepiness and disrupted sleep patterns can be observed due to dysregulation of lateral hypothalamic areas. Obesity, chronic fatigue, headache, and excessive daytime sleepiness can be the result of poor sleep quality. “Primary” hypothalamic sleep dysfunction, including narcolepsy, dysregulated sleep–wake cycles, and hypersomnia, can be observed due to hypothalamic dysfunction. “Secondary” sleep disturbances including obstructive sleep apnea, insufficient substitution medication for arginine vasopressin deficiency (nocturia), or psychosocial factors are sequelae in patients with craniopharyngioma and hypothalamic lesions. Conclusions: Further research on novel treatment approaches for sleep disorders due to hypothalamic syndrome are warranted to improve the outcome after craniopharyngioma. Full article

Collagens make up the main components of the extracellular matrix (ECM), and, in cancer, are often aberrantly secreted by both tumor cells and stromal cells in the tumor microenvironment (TME). Collagen prolyl 4-hydroxylase (C-P4H), an enzyme that hydroxylates proline into 4-hydroxyproline at the Y position of the collagen -X-Y-Gly- triplet motif, is essential for the stability of the mature collagen trimer and collagen secretion. In this review, we summarize the research on the structure and function of C-P4H, the regulation of C-P4H enzyme activity, and the role of overexpression of its α-subunit, P4HA1, in promoting cancer progression as well as its potential as a prognostic marker and therapeutic target. Overexpression of P4HA1 is displayed in almost all solid cancers, including breast, colorectal, and lung cancer, and is associated with cancer progression, worse response to therapy, and poorer patient survival. Characterization of P4HA1 overexpression has demonstrated links to key hallmarks of cancer, not only in the canonical collagen deposition role, but also in non-canonical functions, such as cell stemness, hypoxic response, glucose metabolism, angiogenesis, and modulation of tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment. P4HA1 is thus an attractive target for developing novel targeted therapies to improve treatment response in many cancer types. Full article