Search Results (18,714)

Background/Objectives: Galectin-3 (Gal-3), encoded by LGALS3, is a β-galactoside-binding lectin involved in diverse tumor-associated processes, including immune modulation, cell cycle regulation, and stress adaptation. Despite its known roles in cancer biology, the full extent of its molecular functions and prognostic relevance across tumor types remains incompletely understood. This study aimed to systematically investigate the transcriptomic impact of LGALS3 deletion and assess its clinical significance in cancer. Methods: We analyzed CRISPR-Cas9 knockout transcriptomic data from the SigCom LINCS database to characterize the consensus gene signature associated with LGALS3 loss using functional enrichment analyses. Pan-cancer survival analyses were conducted using TIMER2.0. Differential Gal-3 protein levels in ductal adenocarcinoma and normal pancreatic tissues were evaluated using the Human Protein Atlas. Finally, functional analyses were performed in pancreatic ductal adenocarcinoma (PDAC). Results: LGALS3 deletion across multiple cancer cell lines led to transcriptomic changes involving mitotic progression, stress responses, and axonal guidance pathways. High LGALS3 expression was significantly associated with worse overall survival in lower-grade glioma, PDAC, uveal melanoma, and kidney renal papillary cell carcinoma. LGALS3 knockout in YAPC cells recapitulated the pan-cancer findings, linking LGALS3 to cell morphogenesis and proliferation. Conclusions: These findings identify Galectin-3 as a key regulator of oncogenic programs and a potential prognostic biomarker in PDAC and other malignancies, with implications for therapeutic targeting. Full article

Leprosy is a chronic infectious disease that targets the peripheral nervous system, leading to peripheral neuropathy. Mycobacterium leprae primarily infects Schwann cells, adipocytes, and macrophages, altering their metabolism and gene expression. This study investigates the metabolic interaction between M. leprae and Schwann cells, with a focus on indoleamine 2,3-dioxygenase (IDO), a key enzyme in tryptophan catabolism via the kynurenine pathway. We found that M. leprae induces IDO expression in Schwann cells, suggesting a role in immune modulation and neuropathy. Inhibition of IDO with 1-methyl-L-tryptophan (1-MT) reduced Schwann cell viability and metabolic activity in response to M. leprae. After 24 h of infection, M. leprae impaired mitochondrial membrane potential, although no significant changes in autophagy or mitochondrial ultrastructure were observed by electron microscopy. Interestingly, IDO1 inhibition upregulated the expression of antioxidant genes, including GPX4, NFE2L2, and HMOX1. In conclusion, these findings highlight a central role for IDO in shaping the metabolic and immunological response of Schwann cells to M. leprae infection. IDO induction contributes to immune regulation and cellular stress, while its inhibition disrupts cell viability and promotes antioxidant gene expression. These results position IDO as a potential therapeutic target for modulating host–pathogen interactions and mitigating nerve damage in leprosy. Full article

Tumor mutational burden (TMB) and tumor-infiltrating lymphocytes (TILs) are key biomarkers for predicting immunotherapy responses in cutaneous melanoma. The discordance between brisk TIL morphology and absent cytokine signals complicates immune profiling. We examined the interactions between TMB, TIL patterns, cytokine expression, and genomic alterations to uncover immune escape mechanisms and refine prognostic tools. A structure-based BRAF druggability analysis was performed to anchor the genomic findings in a therapeutic context. Primary cutaneous melanoma cases (N = 205) were classified as brisk (n = 65), non-brisk (n = 60), or absent TILs (n = 80) according to the American association for cancer research (AACR) guidelines. Inter-observer concordance was measured using intraclass correlation. Tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels were graded using immunohistochemistry. Eleven brisk TIL cases lacking TNF-α expression were analyzed using the (Illumina TruSight Oncology 500, Illumina-San Diego, CA, USA). Dabrafenib docking to the BRAF ATP site was performed with Glide SP/XP and rescored with Prime MM-GBSA. Brisk TILs lacking cytokine signals suggested post-translational silencing of TNF-α/IFN-γ. Among the 11 profiled cases, eight exhibited high TMB and copy number alterations, with enrichment of nine metastasis/immune regulation genes. Inter-observer concordance was high (absent TILs, 95%; brisk TILs, 90.7%). BRAF docking yielded a canonical type-I pose and strong ATP pocket engagement (ΔG_bind −84.93 kcal·mol⁻¹). Single biomarkers are insufficient for diagnosis. A multiparametric framework combining histology, cytokine immunohistochemistry (IHC), and genomic profiling enhances stratification and reveals immune escape pathways, with BRAF modeling providing a mechanistic anchor for the targeted therapy. Full article

The aim of the present study is to evaluate the impact of chromium (Cr) supplementation on glucose and lipid metabolism in breast muscle in broilers under heat stress. A total of 220 day-old broiler chicks were reared in cages. At 29 days old, 180 birds were randomly assigned to three treatments (0, 400, and 800 µg Cr/kg, as chromium picolinate) and transferred to climate chambers (31 ± 1 °C, 60 ± 7% humidity) for 14 days. Growth performance, carcass traits, serum biochemical indices, fasting glucose and insulin, homeostasis model assessment of insulin resistance (HOMA-IR), as well as muscle metabolomic profiles and gene expression related to energy and lipid metabolism were analyzed. The results showed that, compared with the heat stress group, the groups supplemented with 400 and 800 µg Cr/kg showed higher dry matter intake and average daily gain, breast muscle ratio, and lower feed conversion ratio and abdominal fat ratio; chickens supplemented with 400 and 800 µg Cr/kg showed significantly lower serum corticosterone (CORT), free fatty acids, and cholesterol levels compared with the heat stress (HS) group (p < 0.05). Fasting blood glucose and HOMA-IR were also significantly reduced, while fasting insulin was significantly increased in the Cr-supplemented groups (p < 0.05). Metabolomic analysis revealed that Cr supplementation regulated lipid and amino acid metabolism by altering key metabolites such as citric acid, L-glutamine, and L-proline, and modulating pathways including alanine, aspartate, and glutamate metabolism, and glycerophospholipid metabolism. Furthermore, Cr supplementation significantly upregulated the expression of Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1 α (PGC-1α), ATP Binding Cassette Subfamily A Member 1 (ABCA1), Peroxisome Proliferator-Activated Receptor α (PPARα), and ATP Binding Cassette Subfamily G Member 1 (ABCG1) in both the hepatic and muscle tissue. This paper suggested that chromium supplementation may enhance energy metabolism and lipid transport like the findings of our study suggested. Full article

Dendrobium officinale (Orchidaceae) is a commonly used medicinal and edible herb. Although its anti-ageing properties have been demonstrated, the underlying mechanisms remain unclear. We employed network pharmacology and molecular biology techniques to systematically explore its anti-ageing mechanisms. An ageing model was established using D-galactose-induced Kunming mice. D. officinale significantly ameliorated ageing-related symptoms, including behavioural impairment and organ index reduction. It enhanced antioxidant capacity by increasing serum T-AOC levels and restoring renal activities of key antioxidant enzymes (SOD, GSH-Px, CAT) while reducing MDA; it suppressed serum TNF-α levels, indicating anti-inflammatory effects. Histopathological examination revealed that D. officinale alleviated D-galactose-induced renal damage, including tubular cell swelling and glomerular capsule widening. Network pharmacology identified 8 core active compounds (e.g., 5,7-dihydroxyflavone, naringenin) and 10 key targets (e.g., HSP90AA1, EGFR, MAPK3). KEGG analysis highlighted pathways including neuroactive ligand–receptor interaction, cAMP signalling, and calcium signalling. Molecular docking confirmed strong binding affinities between core compounds and key targets. Western blotting and immunohistochemistry validated that D. officinale upregulated EGFR, HSP90AA1, ERK, and GAPDH expression in renal tissues. In summary, D. officinale exerts anti-ageing effects by modulating oxidative stress, suppressing inflammation, and regulating multiple signalling pathways. Our findings provide a scientific rationale for its application in anti-ageing interventions. Full article

Background: Parkinson’s disease (PD) is a neurodegenerative disorder for which no curative therapies currently exist. Experimental models employing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) reproduce PD features such as striatal dopaminergic dysfunction and motor deficits. Various MPTP dosing regimens are used to screen drug candidates for PD, but their validity is limited because of the predominant use of young male animals. Sex bias is another issue that is underrepresented in PD research, since females are more susceptible to this pathology. Here, we studied the model of bolus administration of MPTP (30 mg/kg) in aged female mice and assessed its sensitivity to the antioxidants fullerene C₆₀ and fullerenol C₆₀(OH)₂₄, given that oxidative stress is a key contributor to PD. Methods: 12-month-old female C57BL/6 mice received fullerene (0.1 mg/kg/day, via diet) or fullerenol (0.15 mg/kg/day, via drinking water). On day 10, mice were injected with MPTP. We studied tremor, piloerection, and behavior in the pole test, rotarod, pole test, and open field. High-performance liquid chromatography (HPLC) was employed to study dopaminergic neurotransmission, and the expression levels of its molecular regulators and nitric oxide synthase (NOS)-related targets were investigated using RT-PCR in the striatum and cortex. Results: MPTP-challenged mice displayed profound impairment in markers of dopaminergic neurotransmission and cellular distress, and showed disrupted motor behavior and vegetative functions. Antioxidant-treated animals that received a bolus injection of MPTP demonstrated partial preservation of tremor response, dopaminergic parameters, and iNOS and nNOS gene expression, although motor performance in the pole test was only modestly improved. Fullerenol appeared more effective in decreasing MPTP-induced neurochemical changes. Conclusions: The applied MPTP model showed its validity in mimicking PD features and was sensitive to low doses of antioxidants, suggesting its usefulness for screening drugs that target oxidative and nitrosative stress. The neuroprotective effects of fullerene-based compounds suggest their potential utility in the treatment of PD. Full article

Phosphorus is a key macronutrient central to the processes of energy and information storage and exchange in the cell. Single-celled photosynthetic organisms, including microalgae, accumulate intracellular reserves of phosphorus (mostly in the form of polyphosphate) essential for the maintenance of cell homeostasis during fluctuations of external phosphorus availability. The polyphosphate reserves in microalgal cells are formed by polyphosphate polymerases—a ubiquitous enzyme family represented mainly by prokaryotic (PPK-type, typical of prokaryotes, e.g., cyanobacteria) and VTC-type polyphosphate polymerases harbored by eukaryotic microalgae, although certain species possess both PPK and VTC types of the enzyme. This enzyme is important for the environmental fitness of microalgae dwelling in diverse habitats, as well as for the efficiency of microalgae-based systems for the biocapture of phosphate from waste streams and for upcycling this valuable nutrient to agricultural ecosystems via biofertilizer from microalgal biomass. This review summarizes the recent progress in the field of structure, regulation, and functioning of VTC in microalgae. In conclusion, biotechnological implications and perspectives of VTC as a target of microalgal cell engineering and bioprocess design for improved phosphate bioremoval efficiency and culture robustness are considered. Full article

Chronic kidney disease (CKD) is a growing global health burden, strongly associated with cardiovascular disease, the leading cause of mortality in this population. Dyslipidemia is a key metabolic abnormality in CKD, but traditional lipid measures such as total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides often fail to capture the complexity of lipid disturbances in CKD and after kidney transplantation. Apolipoproteins have emerged as more reliable markers of cardiovascular and renal risk. Elevated apolipoprotein B (ApoB), reduced apolipoprotein A1 (ApoA1), and a higher ApoB/ApoA1 ratio are linked to CKD progression, cardiovascular events, and post-transplant complications, including post-transplant diabetes mellitus. Lipoprotein(a), a genetically determined atherogenic lipoprotein, accumulates in CKD due to impaired clearance and further increases cardiovascular risk. Other apolipoproteins, such as APOL1 and APOE, modulate CKD susceptibility through lipid-dependent and independent mechanisms. In addition, proprotein convertase subtilisin/kexin type 9 (PCSK9) has been identified as an important regulator of lipid metabolism, and PCSK9 inhibitors may represent a promising therapeutic option, though evidence in advanced CKD and transplant recipients is still limited, especially regarding their effects on apolipoproteins. This review summarizes current evidence on apolipoproteins and PCSK9 in CKD and transplantation, with attention to their potential as biomarkers and therapeutic targets. Full article

Background and Clinical Significance: In hepatocellular carcinoma (HCC), numerous signaling pathways become aberrantly regulated, resulting in sustained cellular proliferation and enhanced metastatic potential. Tumors that lack PYGO2 may not show the same types of tissue remodeling or regenerative features driven by the Wnt/β-catenin pathway, which could make the tumor behave differently from others that are Wnt-positive. PIK3CA-positive tumors are often associated with worse prognosis due to the aggressive nature of the PI3K/AKT pathway activation. This is linked to higher chances of metastasis, recurrence, and resistance to therapies that do not target this pathway. Case presentation: In this paper we present a rare case of hepatocellular carcinoma with PIK3CA-positive and PYGO2-negative signaling pathways, several key aspects of the tumor’s behavior, prognosis, and treatment options. Although alpha-fetoprotein (AFP) levels were significantly elevated, the CT and MRI examination showed characteristics of malignancy, HCC with secondary hepatic lesions and associated perfusion disturbances. The case particularities and immunohistochemistry features are highlighted in the context of literature review, the PIK3CA mutation suggesting the activation of the PI3K/AKT/mTOR pathway, a critical signaling pathway involved in cell survival, proliferation, and metabolism. Conclusions: Due to the aggressive nature of PIK3CA mutations, close monitoring and consideration of immunotherapy and targeted treatments are of crucial importance. Full article

The MADS-box transcription factors play essential roles in various processes of plant growth and development. Here, we identified 107 MADS-box genes in Osmanthus fragrans Lour. genome (OfMADS), encoding proteins ranging from 61 to 608 amino acids. Phylogenetic analysis classified these genes into five subfamilies: MIKC*, MIKCC, Mα, Mβ, and Mγ, with conserved motif architectures within subfamilies. Tandem and whole-genome duplications were identified as key drivers of OfMADS expansion. Cis-regulatory element analysis revealed enrichment for hormone response and developmental regulatory motifs, implicating roles in growth and flowering processes. Transcriptome dynamics across six floral developmental stages (bolting to petal shedding) uncovered 78 differentially expressed OfMADS genes, including 16 exhibiting flower-specific expressions. Integrated metabolome profiling demonstrated robust correlations between critical OfMADS regulators and scent metabolites. This nexus suggests a potential role of these OfMADS in regulating specialized metabolite biosynthesis pathways. Our multi-omics study provides insights into the regulatory hierarchy of OfMADS in coordinating floral morphogenesis and the accumulation of economically significant metabolites in O. fragrans. These findings establish a foundation for subsequent functional validation and molecular breeding of horticultural traits. Full article

Adipose tissue renewal requires precise coordination of stem/progenitor cell proliferation, preadipocyte commitment, and terminal adipocyte differentiation. T-cadherin (CDH13), an atypical GPI-anchored cadherin, is expressed in adipose tissue and functions as a receptor for high-molecular-weight (HMW) adiponectin—a key adipokine produced by adipose tissue and involved in metabolic regulation. While T-cadherin is implicated in cardiovascular and metabolic homeostasis, its role in adipogenesis still remains poorly understood. In this study, we used the 3T3-L1 preadipocyte model to investigate the function of T-cadherin in adipocyte differentiation. We analyzed T-cadherin expression dynamics during differentiation and assessed how T-cadherin overexpression or knockdown affects lipid accumulation, expression of adipogenic markers, and key signaling pathways including ERK, PI3K–AKT, AMPK, and mTOR. Our findings demonstrate that T-cadherin acts as a negative regulator of adipogenesis. T-cadherin overexpression ensured a proliferative, undifferentiated cell state, delaying early adipogenic differentiation and suppressing both lipid droplet accumulation and the expression of adipogenic markers. In contrast, T-cadherin downregulation accelerated differentiation, enhanced lipid accumulation, and increased insulin responsiveness, as indicated by PI3K–AKT pathway activation at specific stages of adipogenesis. These results position T-cadherin as a key modulator of adipose tissue plasticity, regulating the balance between progenitor expansion and terminal differentiation, with potential relevance to obesity and metabolic disease. Full article

Background: Glutamate transporter 1 (GLT-1) plays a vital role in maintaining glutamate homeostasis in the body. A decreased GLT-1 expression in astrocytes can heighten neuronal sensitivity to glutamate excitotoxicity after traumatic brain injury (TBI). Despite its significance, the mechanisms behind the reduced expression of GLT-1 following TBI remain poorly understood. After TBI, the endocannabinoid 2-arachidonoyl glycerol (2-AG) is elevated several times. 2-AG is known to inhibit key positive transcriptional regulators of GLT-1. This study aims to investigate the role of 2-AG in regulating GLT-1 expression and to uncover the underlying mechanisms involved. Methods: A controlled cortical impact (CCI) model was used to establish a TBI model in C57BL/6J mice. The CB1 receptor antagonist (referred to as AM281) and the monoacylglycerol lipase (MAGL) inhibitor (referred to as JZL184) were administered to investigate the role and mechanism of 2-AG in regulating GLT-1 expression following TBI. Behavioral tests were conducted to assess neurological functions, including the open field, Y-maze, and novel object recognition tests. Apoptotic cells were identified using the TUNEL assay, while Western blot analysis and immunofluorescence were employed to determine protein expression levels. Results: The expression of GLT-1 in the contused cortex and hippocampus following TBI showed an initial decrease, followed by a gradual recovery. It began to decrease within half an hour, reached its lowest level at 2 h, and then gradually increased, returning to normal levels by 7 days. The administration of AM281 alleviated neuronal death, improved cognitive function, and reversed the reduction of GLT-1 caused by TBI in vivo. Furthermore, 2-AG decreased GLT-1 expression in astrocytes through the CB1-CREB signaling pathway. Mechanistically, 2-AG activated CB1, which inhibited CREB phosphorylation in astrocytes. This decreased GLT-1 levels and ultimately increased neuronal sensitivity to glutamate excitotoxicity. Conclusions: Our research demonstrated that the upregulation of GLT-1 expression effectively mitigated neuronal apoptosis and cognitive dysfunction by inhibiting the CB1-CREB signaling pathway. This finding may offer a promising therapeutic strategy for TBI. Full article

Urban industrial complexes have been expanding worldwide, reducing the spatial separation between agricultural, residential, and industrial zones, particularly in developing nations. Urban road dust contamination, a sensitive indicator of urban environmental quality, primarily originates in urbanization and industrialization. Its detrimental impacts on human health arise not only from particulate matter itself but also from toxic and harmful substances embedded within dust particles. Toxic metals in road dust can pose health risks through inhalation, ingestion and contact. To investigate the seasonal patterns, bioaccessibility levels and the potential human health risks linked to toxic metals (Cadmium (Cd), Nickel (Ni), Arsenic (As), Lead (Pb), Zinc (Zn), Copper (Cu), and Chromium (Cr)), 34 dust samples were collected from key roads in proximity to representative industrial facilities in Wuhan’s Qingshan District. The study found that the concentrations of Cd, Pb, and Cu in road dust were within the limits set by the national standard (GB 15618-2018), while Ni and As were not. Seasonally, Ni, As, Pb, Zn, and Cr exhibited higher concentrations during the summer than in other seasons, whereas Cd levels were lowest in spring and highest in autumn, the opposite of Cu. According to the Simplified Bioaccessibility Extraction Test (SBET), the average bioaccessibility rates of toxic metals were Cd > Zn > Cu > Ni > Cr > As > Pb. An improved health risk assessment model was developed, integrating metal enrichment, bioaccessibility, and parameter uncertainty. Results indicated that Cd, Ni, Zn, Cu, As, and Cr posed no significant non-carcinogenic risk. However, for children, the carcinogenic risks of Cd and As were relatively high, identifying them as priority control metals. Therefore, it is recommended to periodically monitor As and Cd and regulate their potential emission sources, especially in winter and spring. Full article

Riparian zones, located at the interface between terrestrial and aquatic systems, are among the most dynamic and ecologically valuable landscapes. These transitional areas play a pivotal role in maintaining environmental health by supporting biodiversity, regulating hydrological processes, filtering pollutants, and stabilizing streambanks. At the core of these functions lie the unique characteristics of riparian soils, which result from complex interactions between water dynamics, sedimentation, vegetation, and microbial activity. This paper provides a comprehensive overview of the origin, structure, and functioning of riparian soils, with particular attention being paid to their physical, chemical, and biological properties and how these properties are shaped by periodic flooding and vegetation patterns. Special emphasis is placed on Mediterranean riparian environments, where marked seasonality, alternating wet–dry cycles, and increasing climate variability enhance both the importance and fragility of riparian systems. A bibliographic study, covering 25 years (2000–2025), was carried out through Scopus and Web of Science. The results highlight that riparian areas are key for carbon sequestration, nutrient retention, and ecosystem connectivity in water-limited regions, yet they are increasingly threatened by land use change, water abstraction, pollution, and biological invasions. Climate change exacerbates these pressures, altering hydrological regimes and reducing soil resilience. Conservation requires integrated strategies that maintain hydrological connectivity, promote native vegetation, and limit anthropogenic impacts. Preserving riparian soils is therefore fundamental to sustain ecosystem services, improve water quality, and enhance landscape resilience in vulnerable Mediterranean contexts. Full article

Nuclear factor of activated T cells 5 (NFAT5), an osmosensitive transcription factor, has been shown to protect against coxsackievirus B3 (CVB3)-induced myocarditis but is susceptible to cleavage by viral proteases. Identifying agents that upregulate NFAT5 may offer a novel antiviral strategy. Cyclodextrins, cyclic oligosaccharides that influence cellular osmolality, are promising candidates. In this study, we demonstrate that NFAT5 is critical for maintaining desmosomal integrity in cardiomyocytes. Cardiac-specific Nfat5-knockout mice showed a significant reduction in desmosomes, as observed by transmission electron microscopy. Furthermore, we identified desmoplakin (DSP), a structural desmosomal protein, as a direct transcriptional target of NFAT5, with reduced expression in Nfat5-knockout mouse hearts and NFAT5-knockdown HeLa cells. Notably, treatment with 5 mM cyclodextrin significantly upregulated NFAT5 expression with minimal cytotoxicity, restored DSP expression, and suppressed CVB3 replication by inhibiting viral RNA transcription, protein synthesis, and virion production. Additionally, cyclodextrin reduced mRNA levels of proinflammatory cytokines interleukin-1 beta and interleukin-8, indicating its potential role as an alleviator of excessive cytokine production. These findings identify NFAT5 as a key regulator of desmoplakin expression and prove cyclodextrin as a dual-functioning agent in counteracting cardiac damage through NFAT5-DSP-mediated protection of desmosome integrity and suppressing proinflammatory cytokine expression in CVB3-induced myocarditis. Full article