Search Results (3,133)

Breast cancer is a heterogeneous disease driven by complex interactions between genetic, hormonal, metabolic, lifestyle, and environmental factors. Among environmental exposures, agricultural pesticides represent potential contributors to breast carcinogenesis through endocrine-disrupting, oxidative, genotoxic, and epigenetic mechanisms. Utilizing a structured search strategy across PubMed, Scopus, and Web of Science, this review provides a critical synthesis of current evidence linking major pesticide classes with breast cancer dynamics, strictly distinguishing preclinical mechanistic findings from human epidemiological data. Special attention is given to endocrine-disrupting pathways involving estrogen receptors and aromatase hyper-induction, alongside oxidative stress, matrix metalloproteinase activation, epithelial–mesenchymal transition, cancer stemness expansion, and therapeutic resistance. We further evaluate the cytoprotective potential and severe bioavailability bottlenecks of dietary phytochemicals in mitigating pesticide-induced damage. Finally, we address critical methodological limitations, such as exposure misclassification, confounding factors, and the gap between micromolar in vitro doses and realistic nanomolar human exposures, stressing that preclinical mechanisms cannot prove direct clinical causality Therefore, integrating prospective multi-omics biomonitoring with cumulative cocktail risk assessments is essential for evidence-based primary prevention. Full article

Lung cancer is among the most fatal malignancies worldwide, with approximately 85% of diagnosed cases being non-small-cell lung cancer (NSCLC). Despite the considerable progress in surgical, chemotherapeutic, radiotherapeutic, and immunological treatments, the prognosis of NSCLC remains poor due to late-stage diagnosis, molecular heterogeneity, treatment resistance, recurrence, and systemic toxicity. Therefore, there is an urgent need to develop more effective and less toxic therapies, and cancer nanotechnology has emerged as a promising approach. Selenium nanoparticles (SeNPs) are a viable option for lung cancer treatment because of their unique physicochemical and biochemical properties. They can be used for targeted drug delivery into cancer cells, as selenium possesses inherent anti-cancer properties, such as the induction of reactive oxygen species (ROS), mitochondrial disruption, DNA damage, cell-cycle arrest, and modulation of several signaling pathways, including PI3K/Akt, MAPK, NF-κβ, STAT3, and p53, leading to cancer cell death and repression of tumor progression. Green synthesis of SeNPs using plant-derived phytochemicals is a sustainable strategy as it allows for simultaneous reduction and stabilization of nanoparticles, with an additional therapeutic phytochemical effect against cancer. Various phytochemicals, such as flavonoids, polyphenols, terpenoids, and alkaloids, have the ability to chelate metal ions and act as reducing agents and stabilizers in the synthesis of SeNPs. The antioxidant, anti-inflammatory, anti-proliferative, and anti-metastatic activities of phytochemicals, along with their ability to inhibit the overexpressed enzymes, e.g., matrix metalloproteinases, in cancer cells, could provide an additional therapeutic benefit. However, the application of SeNPs in practice is limited by their low targeting ability, which results in poor bioavailability due to fast clearance from the bloodstream, reduced tumor accumulation, and poor cellular uptake. Conjugation of SeNPs with tumor-targeting peptides could enhance their delivery into the cancer cells. There is a variety of cell surface receptors that are overexpressed in lung cancer cells and can be used for targeted drug delivery. The most common receptors are EGFR, integrins, gastrin-releasing peptide receptor, neuropilin-1, and transferrin receptor. The ligands for these receptors, including the GE11 peptide for EGFR (epidermal growth factor receptor), RGD for integrins, bombesin for GRPR, and iRGD for neuropilin-1, could be used for targeting, as well as cell-penetrating peptides, such as TAT. This review discusses the current knowledge on the application of functionalized SeNPs for lung cancer treatment, specifically synthetic methods, physicochemical properties, mechanisms of action, and targeting strategies. Particular attention is paid to the combination of the anti-cancer effects of selenium and phytochemicals and their synergistic impact on tumor cell death. In addition, the challenges of the application of SeNPs for lung cancer treatment and possible future developments for functionalized SeNPs as novel therapeutic nanocarriers are discussed. Full article

Endogenous stimuli-responsive gels are designed to alter drug release or matrix behavior in periodontal sites, but their responsiveness is often demonstrated under conditions that may not represent the biological compartment encountered after placement. This comprehensive review examined whether proposed periodontal triggers have been biologically calibrated. Targeted searches of PubMed/MEDLINE, publisher websites, and backward and forward citations identified human studies measuring periodontal pH, proteases, redox conditions, oxygen tension, microbial metabolites, and glucose, together with gel studies using the same cues. Human pH measurements ranged from mildly acidic to alkaline and did not support a universal activation window. Protease-responsive systems had the strongest mechanistic rationale, although recombinant-enzyme testing was not equivalent to native-fluid cleavage. Hydrogen peroxide-responsive gels were generally evaluated under challenge conditions above the limited direct gingival crevicular fluid evidence and without physiological antioxidant buffering. Oxygen-generating systems did not directly sense local oxygen tension. Some glucose challenges overlapped reported human GCF measurements, but calibration to defined periodontal sites and treatment conditions remained unverified. Across trigger classes, preclinical efficacy seldom isolated responsiveness from payload and carrier effects. Future studies should use compartment- and treatment-matched measurements, realistic input–output testing under flow and buffering, patient-derived fluids, and controls that isolate cue-dependent material behavior. Full article

Background/Objectives: The objectives of this study were to investigate the association between tear matrix metalloproteinase-9 (MMP-9) grade and thyroid eye disease (TED) activity and to evaluate its discriminatory performance for active TED. Methods: This retrospective cross-sectional study included 322 patients with TED, including 188 with inactive disease and 134 with active disease. Tear MMP-9 reaction intensity was graded from 0 to 3 using InflammaDry, and active TED was defined as a Clinical Activity Score (CAS) of ≥3. Receiver operating characteristic analysis was used to assess discriminatory performance. Multivariable logistic regression was used to evaluate the independent association between a grade 3 result and active TED, adjusting for age, sex, and serum thyroid-stimulating hormone receptor antibody level. The main outcome measures were the association of tear MMP-9 grade with CAS, area under the receiver operating characteristic curve, adjusted odds ratio, and diagnostic performance for active TED. Results: Tear MMP-9 grade was significantly higher in active than in inactive TED and correlated positively with disease activity (Spearman’s ρ = 0.253, p < 0.001). Its overall discriminatory performance for active TED was modest (area under the curve, 0.619; 95% confidence interval, 0.552–0.682). A grade 3 result was independently associated with active TED (adjusted odds ratio, 8.65; 95% confidence interval, 2.86–26.17; p < 0.001) and demonstrated high specificity (97.9%) but low sensitivity (19.4%), with a positive predictive value of 86.7% and a positive likelihood ratio of 9.12. Conclusions: Tear MMP-9 grade was associated with TED activity and may provide clinically relevant information regarding ocular surface inflammation in TED. Full article

Background/Objectives: Matrix metalloproteinases (MMPs) are enzymes that play a key role in the disruption of blood–brain barrier integrity and neuroinflammatory processes. The objective of this study is to elucidate the contribution of Matrix Metalloproteinase 1 (MMP1) rs1799750 (−1607 1G/2G), Matrix Metalloproteinase 2 (MMP2) [rs243865 (−1306 C > T), rs2285053 (−735 C > T)], and Matrix Metalloproteinase 3 (MMP3) rs3025058 (−1171 5A/6A) genetic variants to the pathogenesis of multiple sclerosis (MS), and to evaluate their potential as genetic markers of neurodegeneration in conjunction with clinical and environmental factors. Methods: The study included 100 MS patients and 100 healthy controls. Genotype distributions of MMP1, MMP2, and MMP3 genetic variants were determined using Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) methods. Participants’ demographic data and clinical histories were recorded. The relevant MMP loci were genotyped, and genotype–allele frequencies as well as haplotype combinations were evaluated. Their associations with clinical parameters were analyzed using Chi-square tests, Odds Ratios (ORs), and One-Way Analysis of Variance (One-Way ANOVA). Results: The rates of heart disease history (13% vs. 4%, p = 0.031), alcohol consumption (29% vs. 14%, p = 0.011), and smoking (35% vs. 21%, p = 0.029) were significantly higher in MS patients compared to the control group. The MMP2 rs243865 (−1306) TT genotype showed a strong positive association with MS, exhibiting approximately 10-fold higher odds of the disease (p < 0.001). Similarly, the MMP3 rs3025058 5A/6A genotype was associated with 2.45-fold higher odds of MS (p < 0.003). Higher odds of the disease were particularly evident with the MMP2 rs243865 (−1306) TT and MMP3 rs3025058 6A/6A combination (OR: 6.769, p < 0.001), followed by the MMP2 rs243865 (−1306) TT and MMP2 rs2285053 (−735) CT combination (OR: 7.169, p < 0.001). No statistically significant association was found between the examined genotypes or haplotypes and clinical parameters, including attack frequency and disease duration (p > 0.05). Conclusions: Our study indicates that MMP2 and MMP3 genetic variants are significantly associated with MS susceptibility, though these variants do not appear to directly influence disease severity parameters such as attack frequency and disease duration. These findings further support the potential involvement of MMPs, particularly in the immunopathological phase of the disease. Consequently, addressing modifiable lifestyle factors in individuals carrying susceptibility-associated genetic profiles and considering early interventions targeting MMP pathways may offer valuable strategic insights for personalized MS management. The data obtained suggest that MMP variations have a potential to be not merely disease markers, but also early-stage therapeutic markers that may be addressed before the first clinical attack occurs. The present study also emphasizes the necessity of transitioning from a reactive approach to a proactive, genetically based personalized medicine paradigm in MS management. Full article

Pulmonary arterial hypertension (PAH) is characterized by progressive vascular remodeling and immune dysregulation. Myeloid angiogenic cells (MACs) are blood-derived mononuclear cells that acquire endothelial-like features at sites of vascular injury, but their transcriptomic phenotype in the pulmonary vascular compartment is poorly characterized. We isolated adherent cells from blood aspirated from the wedged pulmonary artery of four patients with severe PAH during right heart catheterization. The cells were vWF-positive and ACTA2-negative by immunocytochemistry and co-expressed canonical endothelial (CDH5, PECAM1, ERG, FLT1) and myeloid (PTPRC/CD45, CD14, SPI1, IRF8) transcripts, consistent with MAC-like adherent cultures rather than a conventional endothelial population. Bulk RNA sequencing of these cultures was compared with human pulmonary artery endothelial cells (HPAECs) and HUVECs used as endothelial reference cultures. Relative to both references, PAH MACs showed higher transcript levels of cytokines (IL1A, TNF, IL15, IL10) and matrix metalloproteinases (MMP8/9/12); relative to HPAECs, they showed lower levels of Notch-associated genes (DLL4, HEYL). Protein–protein interaction analysis identified modules centered on complement components, myeloid immune receptors and CC chemokines. Because MACs from non-PAH subjects were not available, these differences describe the phenotype of PAH-derived MACs relative to endothelial reference cells rather than a PAH-specific effect. Adherent cultures obtained from wedged pulmonary arterial blood are therefore dominated by a mononuclear phagocyte transcriptional program, which has direct implications for the design of patient-derived pulmonary vascular cell models. Full article

Diabetes impairs multiple stages of the wound-healing process, resulting in chronic, infection-prone wounds that pose a substantial clinical burden. Despite available therapeutic options, effective management remains challenging owing to inadequate treatment efficacy, increasing antimicrobial resistance, and potential adverse side effects. Diabetic wounds exhibit a complex pathological microenvironment characterized by persistent bacterial colonization, hyperglycemia, tissue hypoxia, chronic inflammation, excessive matrix metalloproteinase activity, oxidative stress, and pH dysregulation. Nonetheless, traditional treatment strategies continue to rely largely on passive protection, inadequately addressing the underlying biological mechanisms responsible for impaired healing. Chitosan (CS), a naturally occurring cationic polysaccharide with high biocompatibility, antimicrobial activity, hemostatic properties, and a chemically tuneable structure, represents an attractive platform for advanced wound dressings. This review explores the potential of engineered chitosan-based systems for diabetic wound management through the strategic integration of therapeutic ions (Cu²⁺, Zn²⁺, Mg²⁺, Ag⁺, Mn²⁺), mesoporous silica nanocarriers, and superparamagnetic iron oxide nanoparticles (SPIONs). Unlike previous reviews that have primarily examined these components individually, the present work provides the first comprehensive analysis of their integration within a single multifunctional chitosan-based platform. By systematically evaluating their complementary therapeutic and diagnostic functions, including antimicrobial activity, angiogenic stimulation, oxidative stress modulation, controlled therapeutic delivery, and magnetic field-responsive behavior, this review establishes a unified design framework for the development of next-generation chronic wound dressings. Furthermore, it identifies potential synergistic interactions, key translational challenges, and future research directions required for the development of clinically relevant smart systems. Collectively, this integrated strategy offers a promising approach to overcoming the complex biological barriers that hinder diabetic wound healing. Full article

Osteoarthritis (OA), rheumatoid arthritis (RA), and temporomandibular disorders (TMDs) are heterogeneous joint diseases whose pathophysiology involves inflammation, tissue degeneration, and progressive functional decline. Although their etiologies differ, these conditions display overlapping molecular mechanisms related to extracellular matrix (ECM) remodeling, proteolytic activity, and immune signaling. This systematic review synthesizes current evidence on glycoprotein-associated and proteomic biomarkers identified in synovial fluid and saliva, predominantly derived from protein-level studies, while also evaluating the limited data on glycosylation-specific changes. Using PRISMA guidelines, thirty-eight studies met the review-level eligibility criteria. A structured molecular dataset derived from 20 of these studies was examined through integrative bioinformatics workflows, including network construction, topology analysis, Gene Ontology enrichment, UpSet intersection analysis, and pathway analysis. The analyses revealed a literature-derived disease–protein network characterized by recurrently reported extracellular matrix proteins and matrix metalloproteinases, together with enrichment of collagen-remodeling and regulated proteolytic pathways. Pathway enrichment further indicated shared mechanisms involving ECM regulation, growth-factor signaling, platelet activation, and inflammatory responses based on pathway enrichment. Glycoproteins, particularly proteoglycan 4 (PRG4), together with fibronectin (FN1), cartilage oligomeric matrix protein (COMP), and aggrecan (ACAN), were recurrently represented within the shared OA–RA protein set and were associated with extracellular matrix organization and inflammatory processes. This systematic review synthesizes protein-level biomarker evidence involving experimentally annotated glycoproteins and separately evaluates studies that directly characterized glycan or glycosylation changes. Protein-level network, overlap, and enrichment analyses identified recurrent extracellular matrix remodeling and regulation of extracellular proteolysis, particularly across OA and RA. These analyses describe disease-associated occurrence of glycoproteins and do not by themselves demonstrate altered glycosylation. Direct glycan-level characterization was available in only 5 of the 38 included studies and was largely restricted to O-glycan alterations involving proteins such as PRG4 and MMP3, underscoring the limited availability of glycosylation-specific evidence. Overall, ECM remodeling and the regulation of extracellular proteolysis emerged as the main shared molecular themes across OA and RA. Comparisons involving TMD remained exploratory because of the small evidence base and the predominance of salivary samples, which prevents separation of disease-related from biofluid-related effects. The complementary use of synovial fluid and salivary biomarkers, although requiring validation through paired-sample studies, may facilitate the development of non-invasive diagnostic and monitoring strategies. Full article

Chronic ultraviolet (UV) exposure is a primary driver of skin photoaging, yet safe and effective natural interventions remain limited. This study investigated the anti-photoaging potential and mechanism of Antarctic krill peptides (AKP), a low-molecular-weight oligopeptide mixture (Mw ~331 Da, with 82.82% <500 Da) prepared by enzymatic hydrolysis and membrane fractionation. AKP exhibited excellent skin permeability in vitro. In UV-irradiated human dermal fibroblasts (HDF), AKP alleviated oxidative damage, restored superoxide dismutase activity, reduced malondialdehyde content, and promoted collagen I and XVII secretion, and inhibited matrix metalloproteinase-1 (MMP-1) expression. In a chronic UV-induced mouse photoaging model, topical AKP ameliorated epidermal thickening, dermal collagen loss, and macroscopic wrinkle formation. Skin proteomics revealed that AKP upregulated estrogen receptor Esr1 and androgen receptor Ar, activating the estrogen signaling pathway, which in turn corrected aberrant keratin (Krt5/14/19) and cell-cycle protein (Cdkn1a/Ccna2) expression. Immunohistochemical validation confirmed that AKP inhibited MMP-1/9 overexpression, elevated tissue inhibitor of metalloproteinase-1 (TIMP-1), and increased deposition of collagens I, III, and XVII, thereby restoring extracellular matrix homeostasis. Collectively, these findings demonstrate that AKP combats skin photoaging through estrogen-mediated regulation of matrix degradation and repair. This work fills a mechanistic gap for Antarctic krill-derived peptides and supports their development as natural marine-based anti-aging agents. Full article

Objective: To compare two lipid-lowering therapy strategies involving Ezetimibe and Alirocumab on the vulnerability of atherosclerotic plaque (AP) in patients with acute coronary syndrome (ACS) not achieving the LDL-cholesterol target while on intensive statin therapy. Methods: Combi-LLT-ACS (Patients receiving combination lipid-lowering therapy admitted with the acute coronary syndrome) included 125 patients aged 59 (51; 64) years, of whom 67.2% were men. All underwent percutaneous coronary intervention of the IRA; also, all patients had at least one stenosis < 50% in non-IRA, had high compliance with statins, and did not reached LDL-C level of ≤1.4 mmol/L. Patients underwent Coronary Computed Tomography Angiography (CCTA) to detect vulnerable AP as well as lipid profile and numerous biomarkers: neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), monocyte to high-density lipoprotein ratio (MHR), systemic inflammatory response index (SIRI), matrix metalloprotease type 9 (MMP-9), tissue inhibitor of metalloproteinases type 1 (TIMP-1), Galectin-3 (GAL-3), neutrophil gelatinase-associated lipocalin (NGAL), and C-reactive protein (CRP). Thereafter, they were randomized into two groups, Ezetimibe vs. Alirocumab, on the same visit. The follow-up period was 52 weeks. We used the following CCTA criteria to detect vulnerable AP: positive remodeling, napkin-ring sign, spotty calcification, and low-attenuation plaque. Results: One month after ACS, vulnerable APs were observed by CCTA in 56 patients (44.8%). After 52 weeks, 10 (17.9%) patients showed stabilization of previously vulnerable APs or a decrease in the number of AP vulnerability criteria. At week 52, TC and LDL-C levels decreased significantly over time in both groups. Both arms of therapy demonstrated a positive effect on the inflammatory markers and markers of extracellular matrix remodeling. Direct comparison of changes between groups revealed no statistically significant differences in the number of vulnerability criteria (p = 0.930); however, in the group receiving Ezetimibe, we found a statistically significant change over the observation period (p = 0.032). Conclusions: Among patients with ACS, receiving a high-intensity statin in combination with Ezetimibe or Alirocumab prevented the emergence of new vulnerable coronary lesions over 52 weeks. While direct regression of specific vulnerability criteria was not observed, these therapeutic strategies were associated with a reduction in LDL-C and biomarkers of inflammation and extracellular matrix remodeling. Full article

Plant-derived extracellular vesicle-like nanoparticles (EVNPs) have emerged as bioactive nanomaterials with potential applications in skin biology; however, their isolation from complex plant matrices and their integrated biological effects remain insufficiently characterized. In this study, hemp seed-derived vesicle-like nanoparticles (hs- extracellular VLNPs) were isolated using a multi-step workflow combining pre-clarification, sequential filtration, electrokinetic capture, and tangential flow filtration. The isolated hs-VLNPs exhibited membrane-enclosed vesicle-like morphology, a nanoscale size distribution predominantly within 100–200 nm, and a negative surface charge. hs-VLNPs maintained cellular viability within the concentration range used for most functional assays and exhibited multiple biological activities associated with skin cellular homeostasis. In human dermal fibroblasts, hs-VLNPs increased procollagen type I production and attenuated UVB-induced matrix metalloproteinase-1 (MMP-1) expression following UVB exposure. In HaCaT keratinocytes, hs-VLNPs enhanced scratch closure under non-cytotoxic treatment conditions. Inflammatory mediator responses were cell- and mediator-dependent, with differential effects observed in RAW264.7 macrophages and human dermal fibroblasts rather than uniform suppression of inflammatory mediators. In addition, hs-VLNPs reduced α-melanocyte-stimulating hormone (α-MSH)-induced melanin production while exhibiting little direct inhibition of tyrosinase activity, suggesting that the anti-melanogenic effect may involve cellular regulatory mechanisms rather than direct enzymatic inhibition. Collectively, these findings demonstrate that electrokinetic capture combined with membrane-based filtration enables the enrichment of biologically active vesicle-like nanoparticles from hemp seeds. Rather than exerting a single biological effect, hs-VLNPs modulated multiple interconnected processes involving extracellular matrix homeostasis, cellular migration, immune responses, and melanogenesis, providing a foundation for further investigation of hemp seed-derived EVNPs as plant-derived nanomaterials for skin-related applications. Full article

Background/Objectives: This study evaluated the effects of endodontic irrigation protocols on the apparent elastic modulus and post-treatment total endogenous matrix metalloproteinase (MMP) activity of mineralized radicular dentin. Methods: Radicular dentin beams obtained from 60 extracted single-rooted teeth were allocated to six groups: distilled water, 2.5% sodium hypochlorite, 17% ethylenediaminetetraacetic acid (EDTA), 7% maleic acid (MA), 1% phytic acid (IP6), and 5% IP6. Apparent elastic modulus was determined before and after immersion using three-point bending, while total MMP activity was quantified using a generic colorimetric assay. Data were analyzed using two-way mixed ANOVA, Welch’s ANOVA with Tamhane’s T2 post hoc test, and Spearman’s correlation (α = 0.05). Results: A significant irrigation protocol × time interaction was observed for apparent elastic modulus (p < 0.001), with the greatest reductions following 7% MA and 5% IP6 treatment. Relative total MMP activity differed significantly among the irrigation protocols [Welch’s F(5, 23.05) = 36.285, p < 0.001] and was highest following 7% MA and 5% IP6 treatment. No statistically significant difference in relative total MMP activity was detected between the 1% IP6 and 17% EDTA protocols (p = 0.086). ΔEM% and relative total MMP activity were negatively correlated in the pooled analysis (r_s = −0.679, p < 0.001); however, this association was no longer statistically significant after adjustment for irrigation protocol (partial r_s = −0.146, p = 0.288). Conclusions: Protocol-dependent responses were observed. Low-concentration IP6 warrants further investigation as a potential EDTA alternative, although equivalence and clinical substitutability remain unestablished. Full article

Background/Objectives: Colorectal cancer is a leading cause of global cancer-related mortality. Capecitabine, a 5-fluorouracil prodrug, effectively targets colorectal cancer but suffers from an extremely short half-life, requiring frequent administration. Bilosomes (membrane-stabilized bile salts) are vesicular systems that improve gastrointestinal stability, prevent drug leakage, and extend residence time. This study aimed to fabricate and characterize capecitabine-loaded nanosized bilosomes to overcome the pharmacokinetic limitations and systemic toxicities of conventional capecitabine therapy. By leveraging bile salt-stabilized vesicular systems, we seek to provide sustained capecitabine release, improve gastrointestinal permeability, and enhance therapeutic efficacy against colorectal cancer. We also assessed the anticancer potential of capecitabine-loaded nanosized bilosomes by measuring diagnostic and prognostic biomarkers, including cancer embryonic antigen, carbohydrate antigen 19.9, matrix metalloproteinase-9, and vascular endothelial growth factor A, to evaluate their impact on tumor progression, extracellular matrix degradation, and angiogenesis. Methods: In a 3² full factorial design, nine capecitabine-loaded bilosomes were generated utilizing a central composite design within the framework of response surface methodology. Entrapment efficiency, in vitro drug release and its kinetics, vesicle size, zeta potential, and their kinetics were evaluated. The optimized capecitabine-loaded nanosized bilosomes formulation was subjected to further investigations, such as Fourier transform infra-red spectroscopy, differential scanning calorimetry, X-ray diffractometry study, stability studies, pharmacokinetic study, and in vivo studies, including detection of matrix metalloproteinase-9 and vascular endothelial growth factor A by Real-Time polymerase chain reaction, evaluation of colon biomarker, and examination of colon tissue through histopathology. Results: The prepared capecitabine-loaded bilosomes were nanosized spheres with suitable entrapment efficiency and a high zeta potential. After treatment with capecitabine-loaded bilosomes, the data collected from living organisms indicated a notable reduction in the serum values of carbohydrate antigen 19.9 and cancer embryonic antigen, gene expression values of matrix metalloproteinase-9 and vascular endothelial growth factor A. Histopathological study showed almost complete restoration of colonic features with a lesser extent of epithelial lining and crypt dysplasia. Conclusions: The present study findings demonstrate that capecitabine-loaded bilosomes possess high anti-tumor activity against colorectal cancer. Full article

Background and Objectives: Esophageal atresia (EA) is associated with dysmotility and postoperative morbidity, which may reflect congenital abnormalities of innervation and extracellular matrix (ECM) remodeling. This study compared immunoreactivity for protein gene product 9.5 (PGP 9.5), motilin, three matrix metalloproteinases (MMP-1, MMP-2, and MMP-9), and three tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2, and TIMP-4) among proximal EA, distal EA, and control esophageal tissues. Materials and Methods: Twenty-two formalin-fixed, paraffin-embedded EA tissue specimens (10 proximal and 12 distal segments) and five control specimens were evaluated using semiquantitative immunohistochemistry. Nonparametric methods were used for group comparisons, and associations were assessed using Spearman rank correlations. Results: Epithelial MMP-1 differed among the groups (p = 0.043) and was lower in proximal EA than in controls (pairwise p = 0.036). MMP-2 differed in the epithelium (p = 0.019) and connective tissue (p = 0.022); controls had higher values in the pairwise comparisons. Connective-tissue TIMP-2 also differed among the groups (p = 0.021) and was lower in proximal EA than in controls (pairwise p = 0.0017). PGP 9.5, MMP-9, TIMP-1, and TIMP-4 showed no significant differences in arithmetic mean values among the groups. Motilin’s immunoreactivity was more pronounced in proximal EA, but epithelial immunoreactivity did not differ significantly among the groups. Exploratory, unadjusted correlations among neural, motility-related, and ECM-remodeling markers were observed in EA tissue. Conclusions: The reported differences were specific to the segment and tissue compartment. MMP-2 was lower in distal EA epithelium and in connective tissue from both EA segments than in controls, whereas connective-tissue TIMP-2 was lower in proximal EA. Motilin did not differ significantly among the groups. The correlation findings require confirmation in analyses that adjust for multiple testing. Full article

Monocyte-to-macrophage differentiation and subsequent activation play a crucial role in tissue fibrosis. While the human monocytic cell line THP-1 is widely used as an in vitro model, variations in the use of phorbol 12-myristate 13-acetate (PMA) differentiation often led to inconsistent macrophage phenotypes. Here, we present an optimized protocol yielding mature differentiated THP-1 macrophages (d-THP-1) with stable baseline competence for fibrosis-associated transcriptional change. A protocol consisting of 48 h PMA treatment followed by a 24 h resting phase successfully generated macrophage-like THP-1 cells, confirmed by microscopic assessment and flow cytometric analysis of surface markers. Furthermore, the responsiveness of these optimized macrophages to the chemokine CXCL12 was validated. Following stimulation, the optimized cells exhibited a potentially fibrosis-associated state, characterized by significant early upregulation of matrix metalloproteinase 9 (MMP9) and late upregulation of transforming growth factor-β (TGF-β) measured by RT-qPCR. This reproducible protocol provides a reliable in vitro platform for studying macrophage-mediated fibrotic pathways and screening of therapeutic targets. Full article