Search Results (5,544)

This study developed chitosan (CS)-coated lipid nanoparticles (LNPs) co-loaded with CIP and LUT (CCIPLUTLNPs) as a multifunctional photodynamic therapy (PDT)-enhanced nanoplatform for PCA therapy. The formulations were characterized by particle size, polydispersity index, zeta potential, and encapsulation efficiency. Stability and hemocompatibility were also evaluated. Anticancer activity was assessed in PC-3 cells by measuring cell viability, intracellular reactive oxygen species (ROS) generation under dark and sunlight irradiation, and mitochondrial membrane potential (MMP). In addition, molecular docking was performed against 5α-reductase, androgen receptor (AR), and DNA topoisomerase IIα (TOP2A). Results: The developed LNPs exhibited nanoscale particle size, narrow size distribution, high drug encapsulation efficiency, and a positive surface charge following CS coating. The CS-coated LNPs demonstrated good storage stability and excellent hemocompatibility. Moreover, CCIPLUTLNPs produced the greatest cytotoxicity, enhanced ROS generation, and pronounced mitochondrial membrane depolarization in PC-3 cells. Sunlight irradiation significantly increased ROS production compared with dark conditions, confirming enhanced PDT activity. Molecular docking revealed favorable binding of CIP and LUT to 5α-reductase, AR, and TOP2A, supporting a multitarget anticancer mechanism. Conclusion: CCIPLUTLNPs represent a promising multifunctional nanoplatform that integrates efficient drug delivery, ROS-mediated PDT, and multitarget molecular interactions, offering a potential strategy for improved PCA treatment. Full article

Tendinopathy is a prevalent musculoskeletal condition characterised by chronic inflammatory and degenerative changes. Pulsed electromagnetic fields (PEMFs) represent a promising biophysical therapeutic modality, yet their effects across different inflammatory states of tendinopathy remain poorly characterised. To evaluate PEMF biological effects on human tenocytes, three in vitro models differing in IL-1β dose and duration were tested: acute low-dose (0.1 ng/mL, 96 h), acute high-dose (1 ng/mL, 96 h), and prolonged (0.1 ng/mL, 9 days). At the transcriptional level, PEMFs significantly reduced IL-6 and IL-8 mRNA overexpression in the acute low-dose model and CCL2 upregulation in the prolonged model. At the secretome level, PEMFs reduced GM-CSF and IL-8 secretion in the acute high-dose model, and suppressed CCL2 and CCL5 protein secretion in the prolonged model. MMP activity was not modulated by PEMFs in any condition. PEMFs consistently increased tenocyte proliferation across both the acute models. Finally, in wound healing assays, non-inflamed tenocytes exposed to PEMFs showed significantly enhanced wound closure compared to IL-1β-treated cells across all models; in the acute low-dose model, PEMFs also significantly improved wound closure in IL-1β-treated cells at an early timepoint, whereas no such effect was observed in cells exposed to high-dose or prolonged inflammation. PEMFs exert context-dependent effects, promoting healing primarily during acute or mild inflammation. These findings suggest that the inflammatory stage of tenocytes may influence PEMF responsiveness in vitro, highlighting the importance of considering this variable in the design of future clinical studies evaluating PEMF therapy for tendinopathy. Full article

Background: While live-cell therapies face significant translational hurdles, cell-free secretomes derived from fetal progenitor cells offer a unique, scalable approach natively programmed for scarless tissue repair. Methods: This GLP-compliant study evaluated the therapeutic efficacy spectrum of an off-the-shelf, clinical-grade, intratracheal lyophilized FE002-Lu lung fibroblast conditioned medium (LFCM) across five controlled Wistar rat models of induced lung injury: bleomycin (5 mg/kg), asbestos (100 µg/rat), hyperoxia (100% oxygen exposure), silica (30 mg/rat), and lipopolysaccharide (LPS, 4 mg/kg). Following lung injury induction and symptom onset, symptomatic rats were randomized to receive intratracheal LFCM (low, mid, or high dose) or a vehicle control every 4 days for 28 days. Results: The intervention demonstrated an exceptional safety profile, maintaining 100% survival with no severe procedural toxicity across all cohorts. Across all study arms, LFCM effectively attenuated pulmonary inflammation, reducing pro-inflammatory markers (IL-1β, IL-6, TNF-α, and CINC-1) in bronchoalveolar lavage fluid. Concurrently, high LFCM doses consistently elevated the anti-inflammatory cytokine IL-10. Within the lung tissue, mid- and high doses significantly reduced key pro-fibrotic drivers, including TGF-β1, TIMP-1, WISP-1, and hydroxyproline. Treatments consistently decreased α-SMA expression and pro-fibrotic gene mRNA levels, mitigating pulmonary myofibroblast activation. This correlated with reduced Ashcroft scores and collagen deposition, thereby preserving lung architecture. Notably, the FE002-Lu LFCM treatment exerted a biphasic regulation of extracellular matrix turnover: it elevated Cathepsin-D and MMP-12 in the bleomycin arm to actively clear newly deposited fibrotic debris, while reducing these markers in the hyperoxia and LPS arms to prevent acute collateral degradation of the native lung matrix. In both particulate models (asbestos and silica), the LFCM mid-dose established an optimal therapeutic threshold, avoiding the localized secretome saturation and pro-fibrotic exacerbation occasionally observed at higher doses. Conclusions: Lyophilized FE002-Lu LFCM acts as a potent, pleiotropic biologic that effectively resolves acute pulmonary inflammation and arrests progressive fibrotic remodeling across multiple distinct in vivo models. By overcoming the cold-chain and delivery limitations inherent to pulmonary live-cell therapies, this stable, cell-free secretome represents a highly scalable, “off-the-shelf” candidate poised for non-invasive, aerosolized clinical translation. Full article

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune neurological disorder characterized by pathogenic antibodies against the NMDAR. A systematic protein profiling approach is warranted to identify biomarkers capable of predicting disease status. An Olink proximity extension assay (PEA) profiled 91 inflammation-related proteins from anti-NMDAR encephalitis patients. Disease severity or prognosis were assessed by CASE score or mRS score at 6-month follow-up. Patients were stratified into distinct molecular clusters using unsupervised clustering. Logistic regression models incorporating selected biomarkers were developed to predict disease severity and prognosis, followed by absolute quantification using ELISA. Patients were classified into four consensus clusters. Clusters 1 and 2 corresponded to the mild group, while Cluster 3 represented the severe group, consistent with CASE score above 6. Cluster 4 showed heterogeneous clinical features. Elevated serum levels of IL-10, IL-6, and SIRT2, as well as increased CSF levels of CXCL10, CXCL11, and MMP10, were positively associated with severe disease. Conversely, several proteins including LTA and CCL11, CCL8, TGFB1, CXCL6 were associated with severe disease or unfavorable 6-month outcomes. A logistic regression model combining serum CXCL6 and CCL11 with CSF MMP10 achieved an area under the curve (AUC) of 0.95 for predicting disease severity. Serum CCL11 alone showed predictive value for 6-month prognosis, with an AUC of 0.79. These findings delineate distinct protein signatures associated with clinical heterogeneity of anti-NMDAR encephalitis. Prediction models incorporating multiple biomarkers may provide an approach for disease severity stratification and prognosis forecast. Full article

Background: Lymph node metastasis (LNM) is a major determinant of prognosis in gastric adenocarcinoma. Although lymphovascular invasion (LVI) and perineural invasion (PNI) are established markers of aggressive tumor behavior, their combined association with nodal dissemination has not been systematically evaluated. This study investigated the relationship between invasive histopathologic features and LNM and developed a composite invasion score. Methods: This retrospective study included 395 patients with gastric adenocarcinoma. Clinicopathological analyses involving LNM were performed in the surgical resection cohort. A composite invasion score (0–2) was generated based on the presence of LVI and PNI. Associations with LNM, metastatic lymph node burden, and lymph node ratio (LNR) were evaluated using non-parametric tests and multivariable logistic regression. Predictive performance was assessed using receiver operating characteristic (ROC) analysis. An exploratory external transcriptomic analysis was performed using the GSE15459 dataset. Results: Both LVI and PNI were significantly associated with LNM (both p < 0.001). The composite invasion score showed a stepwise association with nodal dissemination, with median metastatic lymph node counts increasing from 0 in score-0 tumors to 3.5 in score-1 and 9 in score-2 tumors (p < 0.001). After adjustment for pathological T stage, histological grade, Lauren classification, age, and tumor location, the composite invasion score remained an independent predictor of LNM (OR = 4.53, 95% CI: 1.81–13.00, p = 0.002). LNR also increased significantly across score categories (p < 0.001). The composite invasion score demonstrated good discriminatory performance for LNM (AUC = 0.848, 95% CI: 0.773–0.923). The exploratory transcriptomic analysis demonstrated significant upregulation of MMP11, MMP14, and FAP in advanced-stage tumors, consistent with increased extracellular matrix remodeling and stromal activation. Conclusions: A simple composite invasion score integrating LVI and PNI is independently associated with lymph node metastasis and metastatic burden in gastric adenocarcinoma. The accompanying exploratory transcriptomic analysis provides biological context for these clinicopathological findings by demonstrating stage-associated extracellular matrix remodeling rather than direct molecular validation of the proposed score. These findings support the potential utility of the composite invasion score as a postoperative pathology-derived risk stratification tool. Full article

Background: Acute subdural hematoma (ASDH) and chronic subdural hematoma (ChSDH) differ substantially in their pathophysiology, clinical course, and outcomes. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, have been implicated in blood–brain barrier disruption, extracellular matrix remodeling, and inflammatory processes involved in both traumatic brain injury and ChSDH. However, direct comparisons of perioperative MMP profiles between ASDH and ChSDH and their relationships with clinical characteristics remain limited. The aim of this study was to compare perioperative MMP-2 and MMP-9 concentrations in patients with ASDH and ChSDH and explore their associations with selected clinically relevant parameters. Methods: Thirty patients undergoing surgical treatment for subdural hematoma were prospectively enrolled, including 10 patients with ASDH and 20 with ChSDH. Serum samples were collected before surgery and on postoperative day 3, and hematoma content was obtained intraoperatively. MMP-2 and MMP-9 concentrations were measured using enzyme-linked immunosorbent assay. Results: Patients with ASDH had significantly higher MMP-9 concentrations in hematoma content (p = 0.002) and postoperative serum (p = 0.029) than patients with ChSDH, whereas MMP-2 concentrations did not differ significantly between the groups. In the ChSDH group, both MMP-2 and MMP-9 concentrations were significantly lower in hematoma content than in preoperative and postoperative serum, while no significant perioperative changes were observed in patients with ASDH. Higher MMP-2 concentrations in hematoma content were associated with lower leukocyte counts and smaller midline shift, whereas higher hematoma MMP-9 concentrations were associated with lower APTT and CRP concentrations after FDR correction. These findings suggest distinct perioperative MMP-2 and MMP-9 profiles in acute and chronic subdural hematomas. Conclusions: This study provides a direct comparison of perioperative MMP-2 and MMP-9 profiles in serum and hematoma content between patients with ASDH and ChSDH while also exploring their associations with selected clinically relevant parameters. Full article

Differences in the composition, microstructure, infrared spectral characteristics, and enzymatic hydrolysis properties of rice bran protein extracted by four methods were investigated, and the antioxidant and anti-photoaging activities of peptides derived from the resulting hydrolysates were further evaluated. Rice bran protein obtained via ultrasonic pretreatment combined with alkaline solublilization and acid precipitation (URP) exhibited relatively high purity (59.17%) and extraction yield (47.61%), together with increased surface porosity, enhanced hydration capacity, and improved enzymatic hydrolysis performance. The URP hydrolysate (URPP) showed a protein content of 81.00%, a degree of hydrolysis of 33.57%, and marked antioxidant activity (ABTS, 684.21; ORAC, 2016.15 μmol TE/g sample). The identified peptides were predominantly short and enriched in hydrophobic amino acids. Structural analysis suggested that the indole N-H group of tryptophan may play an important role in the antioxidant activity of these peptides. Moreover, these peptides alleviated UVB-induced photoaging in HaCaT cells by reducing oxidative stress and inflammatory responses and downregulating the mRNA expressions of AP-1, MMP-1 and MMP-3. Overall, these findings reveal an association between the extraction method, structural characteristics, and enzymatic hydrolysis properties of rice bran protein and the biological activities of its derived peptides, providing a basis for the high-value utilization of rice bran protein and the development of antioxidant and anti-photoaging functional ingredients. Full article

Background and Objectives: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterised by recurrent nodules, abscesses, sinus tract formation, and tissue remodelling. Increasing evidence suggests that oxidative stress contributes to HS pathogenesis; however, the role of the Nrf2–Keap1–Sestrin-2 axis and its interaction with matrix remodelling pathways remains poorly understood. This study aimed to evaluate serum levels of Nrf2, Keap1, Sestrin-2, asprosin, MMP-1, and TIMP-1 in patients with HS and to investigate their potential roles in disease pathophysiology. Materials and Methods: A total of 26 patients with hidradenitis suppurativa and 20 healthy volunteers were enrolled in the study. Serum biomarkers were measured in patients with HS and healthy controls. In addition to conventional statistical analyses, multivariate analyses, including PCA, PLS-DA, VIP scoring, correlation mapping, ROC analysis, heatmap visualisation, and biplot assessment, were performed to characterise biomarker interactions and discriminatory performance. Results: HS patients exhibited significantly increased serum asprosin, Keap1, and MMP-1 levels, whereas Nrf2, Sestrin-2, and TIMP-1 levels were significantly reduced compared with controls. Multivariate analyses demonstrated clear separation between patient and control groups within the cohort, indicating a distinct biochemical signature associated with HS. VIP analysis identified Nrf2, Sestrin-2, and TIMP-1 as the most influential variables contributing to group discrimination. Within the HS group, none of the pairwise biomarker correlations remained statistically significant after Benjamini–Hochberg false discovery rate (FDR) correction. ROC analysis showed diagnostic performance for Nrf2 and Sestrin-2. Conclusions: These findings suggest that alterations in serum markers related to the Nrf2–Keap1–Sestrin-2 axis and the MMP-1/TIMP-1 balance are associated with oxidative stress, inflammation, and tissue remodelling in HS. Nrf2 and Sestrin-2 may represent candidate biomarkers; however, given the modest sample size and single-centre design, their discriminatory performance should be considered exploratory and requires confirmation in larger independent cohorts. Full article

Background/Objectives: Glioblastoma (GBM) is the most aggressive and lethal primary brain tumor, and elucidating the molecular determinants of its malignant progression is essential for improving patient outcomes. NTAN1 encodes N-terminal asparagine amidase 1, a component of the N-degron pathway involved in selective protein turnover; however, its role in GBM remains unclear. This study aimed to investigate the clinical significance and biological function of NTAN1 in GBM. Methods: Integrated analyses of The Cancer Genome Atlas (TCGA) transcriptomic and clinical data were performed, together with tissue microarray validation, to assess the association between NTAN1 expression and prognosis in GBM. Immunohistochemical analysis of GBM specimens was conducted to evaluate NTAN1 protein expression. Functional studies, including NTAN1 knockdown and overexpression experiments, were used to examine its effects on GBM cell proliferation, clonogenic growth, migration, and invasion. An orthotopic GBM model was established to assess the effect of NTAN1 inhibition on tumor growth. Transcriptomic analysis was further performed to explore the molecular changes associated with NTAN1 knockdown. Results: Elevated NTAN1 expression was associated with poor survival in GBM. Immunohistochemical analysis further demonstrated that high NTAN1 protein expression predicted unfavorable prognosis. Functional studies showed that NTAN1 knockdown inhibited GBM cell proliferation, clonogenic growth, migration, and invasion, whereas NTAN1 overexpression promoted these malignant phenotypes. In an orthotopic GBM model, NTAN1 inhibition significantly reduced tumor volume. Transcriptomic analysis showed that NTAN1 knockdown was associated with reduced expression of invasion-related genes, including SPINK1, MMP1, and LIF, and with enrichment changes in inflammation-associated pathways, suggesting that NTAN1 may promote GBM progression through pro-invasive molecular programs. Conclusions: Collectively, these findings identify NTAN1 as a potential promoter of GBM malignant progression and a prognostic biomarker of poor outcome. Full article

Skin photoaging is closely associated with oxidative stress, inflammatory responses, and dysregulated collagen metabolism. Paeonol (Pae) possesses antioxidant and anti-inflammatory activities; however, its poor water solubility and short skin retention time limit its topical application. In this study, a transdermal delivery system based on a carboxymethyl chitosan (CMCS)/Carbomer 940 (Carb940) composite gel loaded with hydroxypropyl-β-cyclodextrin inclusion complexes of paeonol (Pae-CD) was developed. Pae-CD was prepared using an ultrasound-assisted saturated aqueous solution method, and the physicochemical properties, sustained-release behavior, transdermal permeation, antioxidant activity, and safety of Pae-CD/gel were evaluated. Furthermore, a mouse model of skin photoaging induced by combined ultraviolet A (UVA)/ultraviolet B (UVB) irradiation was established to investigate its reparative effects in vivo. The results showed that Pae-CD/gel exhibited a homogeneous three-dimensional porous structure, favorable sustained-release characteristics, enhanced skin retention capacity, and good cellular compatibility. In vivo experiments demonstrated that Pae-CD/gel markedly ameliorated ultraviolet-induced skin dryness, abnormal epidermal thickening, and dermal collagen loss. It also reduced oxidative stress and inflammatory factor levels, down-regulated matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-3 (MMP-3) expression, and promoted the restoration of collagen type I (COL-1) and hydroxyproline (HYP) levels. Systemic safety evaluation revealed no obvious toxicity. In summary, Pae-CD/gel exerts antioxidant and anti-inflammatory effects and regulates collagen metabolism by enhancing transdermal delivery and local retention, thereby providing a safe and effective topical delivery strategy for the repair of skin photoaging. Full article

Background/Objectives: Exposure to lead (Pb) is a serious public health concern for which there is no safe level. The aim of this study was to investigate the toxicity of Pb to undifferentiated (uSH-SY5Y) and differentiated (dSH-SY5Y) human neuroblastoma cells and to evaluate gene transcription in response to sub-lethal lead exposure. Methods: Pb was applied to uSH-SY5Y and dSH-SY5Y cells across a concentration range of 0–5 mM for 4, 6, and 24 h, and cell viability was assessed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase assays. Results: Pb induced a significant concentration- and exposure-dependent reduction in cell viability. Pb significantly impacted cellular bioenergetics and reduced ATP production in a concentration- and exposure duration-dependent manner, triggering elevated levels of deleterious reactive oxygen species. Transcriptomic profiling in dSH-SY5Y cells after a sub-lethal 24 h exposure to 1.25 mM Pb revealed 757 upregulated and 2206 downregulated genes. From Gene Ontology and KEGG pathway enrichment analysis, biological processes were predominantly associated with immune and inflammatory processes, including cytokine-mediated signalling. Upregulated differentially expressed genes (DEGs) included those for PI3K/Akt and cytokine signalling, and downregulated DEGs included genes linked to spinocerebellar ataxia, mitophagy, cytokine receptor interaction and cellular metabolism. Protein–protein interaction analysis identified six key hub-upregulated genes with a primarily inflammatory focus (CD44, CXCR4, PTGS2, IL1β, TNF, MMP9) and one downregulated gene (CD4) as potential regulators of Pb-induced cellular responses. Disease association analyses revealed links to chemical carcinogenesis and neurodegenerative diseases. Conclusions: Collectively, these findings provide molecular insights into Pb-induced neurotoxicity and highlight a network of genes that converge on neurological and inflammatory pathways, which are candidates for further mechanistic investigation and possible therapeutic targeting following Pb poisoning. Full article

Skin photoaging, primarily driven by UVA radiation, is characterized by the accumulation of senescent fibroblasts and the degradation of the extracellular matrix (ECM). While the roles of reactive oxygen species (ROS) and matrix metalloproteinases (MMPs) are well-documented, the regulatory impact of post-translational glycosylation in this process remains poorly understood. We established a UVA-induced photoaging model in human dermal fibroblasts (HDFs) and employed bulk mRNA-seq and high-throughput lectin microarrays to profile glycomic alterations. The functional role of the sialyltransferase ST6GAL1 was investigated through pharmacological inhibition of cellular sialylation (3Fax-Neu5Ac), siRNA-mediated knockdown, and gain-of-function overexpression. Mechanistic insights were gained via RAS-ERK pathway analysis and validated in a 3D reconstructed human full-thickness skin model (T-Skin™). Glycomic profiling revealed that UVA irradiation triggers a broad increase in α2,6-sialylation in HDFs. We identified ST6GAL1 as the primary enzymatic driver of this remodeling, with its expression upregulated in both photoaged HDFs and 3D skin models. Functional assays demonstrated that ST6GAL1 overexpression induces hallmark features of photoaging, including p16, MMP and γ-H2AX upregulation, G0/G1 cell cycle arrest and increased SA-β-gal activity. Conversely, pharmacological or genetic inhibition of ST6GAL1 effectively mitigated the photoaged phenotype. Mechanistically, ST6GAL1 regulates the expression of p16 via the activation of the RAS-ERK signaling cascade. Our study identifies ST6GAL1-mediated α2,6-sialylation as a novel functional hallmark of skin photoaging, highlighting the association of ST6GAL1 with the RAS-ERK-p16 axis as a potential regulator for targeting UVA-induced skin photoaging and dermal senescence. Full article

Background: In recent decades, the incidence of colorectal cancer (CRC) has been rising worldwide. CRC ranks second in cancer-related mortality. The identification of reliable biomarkers for early diagnosis and prognosis prediction, along with a deeper understanding of the underlying molecular events, holds substantial promise for improving patient outcomes. The tissue inhibitor of the metalloproteinase 1 (TIMP1) gene is overexpressed in various gastrointestinal malignancies and contributes to tumor progression. However, its role in regulating the CRC tumor immune microenvironment (TIME) and its potential as a clinically actionable prognostic biomarker remain unclear. Methods: To probe how TIMP1 acts as a prognosis-related candidate biomarker in colorectal carcinoma, TCGA-derived datasets were adopted to conduct Kaplan–Meier survival assessment. We also investigated the connection between the expression abundance of TIMP1 and the infiltration of immune populations and intratumoral lymphocytes; furthermore, immune checkpoint-related genes were systematically assessed across multiple tumor types via the TISIDB and TIMER2.0 platforms, with particular emphasis on CRC. We adopted the ESTIMATE scoring system to figure out how TIMP1 gene expression correlates with the phenotypic properties of the colorectal-cancer TIME. We relied on the limma toolkit for the screening of differential transcripts from high-TIMP1 and low-TIMP1 cohorts. Enrichment assessments covering Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes entries were then carried out to predict the potential biological pathways associated with TIMP1. We constructed the protein–protein interaction map for TIMP1-interacting partners via the STRING repository. To further explore TIMP1-correlated genes, we performed Venn diagram intersection analysis combined with Spearman’s correlation test. Finally, quantitative reverse-transcription PCR was then implemented to detect TIMP1 messenger-RNA abundance inside the RKO colorectal carcinoma cell line as well as normal colonic epithelial CCD-18Co cells, which offered in vitro experimental verification for our bioinformatic outcomes. Results: According to outcome data, TIMP1 transcripts were markedly up-regulated in CRC specimens and cell lines relative to normal samples. Elevated TIMP1 expression served as a poor-prognosis indicator for overall survival (hazard ratio [HR] = 0.43, 95% confidence interval [CI] = 0.29–0.64, p < 0.001) and disease-specific survival (HR = 0.39, 95% CI = 0.22–0.68, p = 0.001) among colorectal-carcinoma patients. TIMP1-high and TIMP1-low groups exhibited notable differences in immune cell infiltration (CD8⁺ T, macrophage, mast, neutrophil, B, monocyte, dendritic, and CD4⁺ T cells). TIMP1 expression was also significantly correlated with tumor-infiltrating lymphocytes, key immune checkpoint genes (e.g., CD274 [PD-L1] and CTLA4), and immunomodulatory chemokines (e.g., CCL3 and CCL5). Twelve TIMP1-interacting DEGs were selected: COL5A1, FN1, PRG4, and a cluster of nine MMPs (MMP1/2/3/7/8/9/11/13/14), all of which showed significant positive correlations with TIMP1 (r = 0.31–0.63, all p < 0.001). Conclusions: TIMP1 expression correlates with features of the tumor immune microenvironment and extracellular matrix remodeling in CRC, suggesting that TIMP1 shows potential as a candidate biomarker. However, its potential as a therapeutic target warrants further experimental investigation. Full article

Cancer metastasis, characterized by the dissemination of malignant cells from the primary tumor to distant organs, remains the leading cause of cancer-related mortality in solid tumors. In colorectal cancer (CRC), increasing attention has been directed toward therapeutic strategies aimed at suppressing cancer cell migration and invasion rather than solely reducing tumor mass, giving rise to the concept of migrastatic therapies. In the present study, green-synthesized silver nanoparticles (AgNPs), previously obtained using aqueous extracts of Filipendula ulmaria (L.) Maxim. and Salvia verticillata L., were evaluated for their antimigratory and anti-inflammatory potential in human colorectal carcinoma HCT-116 cells. Treatment with AgNPs induced considerable perturbations in cellular redox homeostasis, as evidenced by increased intracellular reactive oxygen species (ROS), lipid peroxidation (LPO), glutathione (GSH), and nitric oxide (NO) levels. These redox alterations were accompanied by a significant inhibition of cancer cell migration, together with reduced expression of matrix metalloproteinases MMP-2 and MMP-9, key mediators of extracellular matrix remodeling associated with tumor progression. AgNP exposure was associated with activation of the cytoprotective transcription factor Nrf-2 and suppression of the pro-inflammatory NF-κB/COX-2 signaling axis, indicating coordinated modulation of redox-sensitive pathways linked to tumor cell motility and inflammatory responses. Collectively, these findings demonstrate that green-synthesized AgNPs derived from F. ulmaria and S. verticillata exert multi-level regulatory effects on redox balance, inflammatory signaling, and migration-associated molecular markers in colorectal cancer cells. This study supports their potential as promising migrastatic nanocarriers for further investigation in colorectal cancer research. Full article

Background: Aggression and violence are complex behavioral phenomena with substantial biological underpinnings involving immune activation and lipid metabolism. Previous evidence has linked inflammatory signaling and altered cholesterol homeostasis to impulsive and antisocial behaviors. The present exploratory study investigated differential gene expression patterns associated with severe violent offending and their relationship with aggression-related phenotypes. Methods: Whole-blood samples from 19 male severe violent offenders and 11 healthy controls were analyzed using Clariom S gene expression arrays followed by qPCR validation. Participants additionally completed psychometric assessments including the State Trait Anger Expression Inventory-II (STAXI-II), the Psychopathic Personality Inventory-Revised (PPI-R), and the Appetitive and Facilitative Aggression Scale (AFAS). Results: Differential expression analysis identified 833 significantly dysregulated genes (FDR < 0.1; fold change ≥ 1.5) in violent offenders relative to controls. Among the most strongly altered genes were IL1B, TLR4, PTGS2 (COX-2), ABCA1, IL6R, PRF1, and MMP9. qPCR validation confirmed significant upregulation of MMP9, PTGS2, IL6R, and PRF1. Gene x behavior analyses demonstrated significant associations between PTGS2 expression and reactive as well as outwardly directed aggression, while MMP9 expression correlated with psychopathy-related traits. Furthermore, several lipid metabolism-related genes, including ABCA1, ABCG1, NPC1, DGAT2, and TLR4, showed expression patterns suggestive of altered intracellular lipid trafficking and lysosomal lipid accumulation. ABCA1 expression correlated positively with outward anger expression (STAXI-II), whereas ABCG1 and TLR4 were negatively associated with inwardly expressed anger (STAXI-II). Conclusions: These findings support a model in which innate immune activation and dysregulated lipid metabolism contribute to aggression-related phenotypes and severe violent behavior. Although exploratory and limited by sample size, the results highlight potential molecular pathways underlying pathological aggression and warrant further investigation in larger cohorts. Full article