Search Results (3,450)

Objectives: Oral leukoplakia (OL) is the most prevalent oral potentially malignant disorder and requires accurate diagnosis, safe excision, and reliable margin evaluation to minimize recurrence and malignant transformation. Diode laser excision is increasingly adopted due to its precision and favorable clinical outcomes; however, laser-induced thermal effects at surgical margins raise concerns regarding tissue integrity and histopathological reliability. This study aimed to evaluate optical coherence tomography (OCT) as a real-time, high-resolution, non-invasive imaging modality for assessing peri-incisional thermal effects during diode laser excision of non-dysplastic OL. The primary objective was to validate OCT for ultrastructural and morphometric tissue analysis while ensuring preservation of diagnostic readability. Methods: A single-center observational case series was conducted at the University of Turin. Thirty patients with clinically and histopathologically confirmed oral leukoplakia without epithelial dysplasia were enrolled and allocated to two groups: 15 lesions excised using a 980 nm diode laser in continuous-wave contact mode (laser group) and 15 lesions removed by conventional scalpel biopsy (control group). Laser excisions were performed with standardized parameters and a circumferential safety margin of 5 mm. Immediately after excision, specimens underwent ex vivo spectral-domain OCT (SD-OCT) imaging to evaluate the epithelial and connective tissue microarchitecture at surgical margins and central lesion areas. OCT acquisition sites were precisely correlated with histological sections. Quantitative OCT measurements of epithelial thickness, lamina propria thickness, and laser-induced thermal alterations were compared with corresponding histological findings. Results: OCT consistently provided high-resolution visualization of oral mucosal microarchitecture in both groups, allowing clear identification of epithelial stratification, basement membrane continuity, and lamina propria organization. In the laser group, OCT detected superficial optical alterations at the surgical margins consistent with laser-induced thermal effects, while deeper tissue layers remained structurally readable. Histological analysis revealed mean epithelial and connective tissue thermal alterations of 288.9 μm and 430.3 μm, respectively. OCT-derived measurements showed high concordance with histology, with an overall agreement of 88.5% and no statistically significant differences between OCT and histological assessments. Importantly, laser-induced thermal effects did not impair definitive histopathological diagnosis in any specimen. Comparison with the control group confirmed preserved tissue architecture in scalpel-excised samples and highlighted OCT sensitivity in detecting laser-related structural remodeling. Conclusions: OCT proved to be a reliable, non-invasive imaging technique for real-time assessment of diode laser-induced thermal effects during OL excision. The technique accurately delineated tissue microstructure and surgical margins without compromising histopathological interpretation. Integration of OCT into the laser-assisted management of oral potentially malignant disorders may enhance surgical precision, optimize margin control, reduce diagnostic uncertainty, and support individualized follow-up strategies. Full article

Influenza A virus (IAV) infection constitutes a major public health threat. Severe influenza virus infection can induce intense inflammatory responses and lung injury, leading to serious clinical symptoms or even death. The utility of current anti-influenza drugs is often limited by side effects and the emergence of drug-resistant strains. Based on the critical role of L-type voltage-gated calcium channels (L-VGCCs) in influenza virus replication, this study investigates the antiviral activity and mechanism of verapamil, a classic L-type calcium channel antagonist, against H1N1-UI182 virus. Verapamil, an L-type calcium channel blocker, is widely used in the treatment of cardiovascular diseases and has a well-established safety profile. Through molecular dynamics (MD) simulation and network pharmacology analysis, we predicted the stable binding mode of verapamil to the target protein (PDB id: 6JPA) and its potential multi-target network. In vitro, verapamil exhibited antiviral activity against H1N1-UI182 in MDCK cells, enhancing the survival rate of infected cells and reducing viral nucleoprotein (NP) expression. In a lethal H1N1-UI182 infection mouse model, verapamil treatment markedly improved survival rates, alleviated weight loss and lung pathological damage, exhibiting a dose-dependent protective effect. Lung tissue analysis showed that verapamil effectively reduced the lung index and viral load, suppressed the activation of the Nuclear factor kappa B (NF-κB) signaling pathway, and decreased the expression of key inflammatory factors, thereby mitigating the cytokine storm. A comparison of administration regimens indicated that pre-treatment yielded optimal efficacy, suggesting verapamil acts primarily during the early stage of the viral life cycle. This study systematically elucidates that verapamil exerts antiviral and immunomodulatory effects by regulating the NF-κB pathway. Network pharmacology analysis suggested the potential involvement of multiple targets and pathways, including EGFR, SRC, and phospholipase D signaling, providing hypotheses for future mechanistic investigation. This paper supports a drug repurposing strategy against drug-resistant influenza viruses and highlights its significant potential for clinical translation. Full article

Pigs are a major source of animal protein and an important model for studying domestication, adaptation, and the genetics of complex traits. Over the past decade, pig genomics has progressed from generating reference assemblies and variant catalogues toward reconstructing population history and interpreting phenotypic divergence with greater resolution. Improvements in reference continuity, breed-matched assemblies, and pangenome/graph representations reduce reference bias in repeat-rich and structural-variant-prone regions, strengthening cross-population comparisons and fine-mapping across cohorts. Time-stratified ancient genomes provide an explicit temporal framework for evaluating lineage turnover and gene flow and support a multi-stage, network-based view of domestication. In parallel, genetic analyses of growth, carcass composition, meat quality, and disease resilience increasingly integrate association signals with regulatory annotation, gene expression, and tissue- or stage-specific context. Across these lines of work, maintaining comparability across reference frameworks remains central, including stable coordinate systems, robust imputation resources, and reproducible approaches for structural-variant genotyping. Together, these developments support more consistent inference and interpretation while providing a clearer basis for translation in breeding and biomedical research with attention to genetic diversity. Full article

Background/Objectives: This study aimed to evaluate the autoregulatory capacity of optic nerve head (ONH) tissue blood flow in response to intraocular pressure (IOP) fluctuations during vitrectomy in patients with proliferative diabetic retinopathy (PDR). We hypothesized that impaired autoregulation of ONH tissue blood flow in response to intraoperative IOP fluctuations could contribute to subsequent ONH atrophy and the development of visual field defects in PDR patients following vitrectomy. Methods: We included five eyes from five patients with PDR (mean age 70.6 ± 9.0 years) undergoing 25-gauge pars plana vitrectomy. ONH tissue blood flow was quantitatively assessed using intraoperative laser speckle flowgraphy. Mean blur rate in the tissue area (MT), an indicator of ONH tissue blood flow, was measured at baseline (infusion pressure 0 mmHg), during sustained elevation to 25 mmHg (at 5 and 10 min), and 1 min after return to baseline (11 min). IOP was modulated using the IOP Control system of the Constellation platform. Results: Elevation of IOP to 25 mmHg significantly reduced ONH tissue blood flow, with MT decreasing by 29% at 10 min compared with baseline (p < 0.05, Dunn’s multiple comparisons test). After IOP returned to baseline, MT significantly recovered compared with the 10 min measurement (p < 0.05) and returned to levels not significantly different from baseline (p > 0.05). Conclusions: MT decreases during intraoperative IOP elevation in PDR undergoing vitrectomy, but recovers after the return to baseline pressure, suggesting preserved short-term autoregulatory capacity. Careful IOP management during vitrectomy remains important in eyes with PDR. Full article

Background and objectives: Head and neck cancer patients frequently undergo radiotherapy, which can affect the properties of dental hard tissues. This study aimed to evaluate the effects of root canal treatment, radiotherapy, and sonic activation during irrigation on the fracture resistance of mandibular anterior teeth. Methods: 80 extracted mandibular anterior teeth were randomly divided into five groups: untreated control (Group I); root canal treatment without radiotherapy or sonic activation (Group II); root canal treatment without radiotherapy but with sonic activation (Group III); root canal treatment with 70 Gray (Gy) radiotherapy and sonic activation (Group IV); and root canal treatment with radiotherapy but without sonic activation (Group V). Radiotherapy was administered in fractionated doses (2 Gy/day, 5 days/week) over 7 weeks. Following instrumentation, root canal obturation was performed accordingly. Fracture resistance was measured using a universal testing apparatus with vertical loading until fracture. Statistical analyses included Shapiro–Wilk normality testing followed by appropriate non-parametric Kruskal–Wallis test followed by Dunn’s post hoc test with Bonferroni correction for multiple comparisons. Results: All root canal-treated groups exhibited significantly lower fracture resistance compared to the untreated control group [1572.3 (1217.0–1841.2) N, p < 0.05]. No statistically significant differences were observed between irradiated and non-irradiated groups (p > 0.05). Similarly, sonic activation during irrigation did not significantly affect the fracture resistance values (p > 0.05). Conclusions: Under the specific conditions of this in vitro protocol, fractionated radiotherapy and sonic activation did not demonstrate statistically significant effects on fracture resistance in mandibular anterior teeth, while endodontic procedures reduced fracture resistance. Full article

Objectives: This study aimed to characterize the expression patterns and interrelationship of key fibrosis-related markers—TGF-β1, SMAD2, SMAD3, and fibronectin—in human endometrial tissue, and to explore their potential diagnostic relevance in differentiating intrauterine adhesions (IUAs) from cesarean scar defects (isthmocele), with a particular focus on underlying fibrotic remodeling processes. Methods: Endometrial samples were obtained from women diagnosed with IUAs, isthmocele, or without uterine pathology. Total RNA was extracted from all specimens, and gene expression levels were quantified using real-time quantitative polymerase chain reaction (PCR). Statistical analyses included intergroup comparisons, parametric and non-parametric correlation analysis, multivariable linear and logistic regression models, and receiver operating characteristic (ROC) curve analysis to explore the discriminatory potential of the evaluated markers. Results: Significant positive correlations were observed across the study population between SMAD2 and SMAD3 (r = 0.892; p = 0.001), SMAD2 and TGF-β1 (r = 0.697; p = 0.001), and SMAD3 and TGF-β1 (r = 0.910; p = 0.001), indicating coordinated activation of profibrotic signaling pathways. ROC curve analysis showed high discriminatory performance for isthmocele across all evaluated markers, with area under the curve (AUC) values of 0.976 for SMAD3, 0.961 for TGF-β1, 0.913 for fibronectin, and 0.928 for SMAD2 (all p = 0.001). In contrast, although elevated expression levels of fibrotic markers were observed across different American Fertility Society (AFS) stages in IUAs, these differences did not reach statistical significance. Conclusions: This study provides molecular evidence distinguishing isthmocele from IUAs with respect to fibrosis-related signaling in human endometrial tissue. The markedly elevated and coordinated expression of TGF-β1, SMAD2, SMAD3, and fibronectin in isthmocele reflects activation of post-cesarean fibrotic remodeling pathways. However, given the limited sample size and the exploratory nature of the analyses, larger cohorts and future studies are required to validate these findings and to allow extrapolation of the results to the general population. At this stage, these biomarkers should therefore be regarded as indicators of underlying pathophysiological processes. Full article

Background: In this study, we aimed to compare metabolomic profiles, biodistribution, and detoxification patterns of the novel SN-38 derivative NMe with irinotecan (IR), and to identify NMe-specific metabolites to evaluate its preclinical pharmacokinetic advantages. Methods: In vivo ADME studies were conducted for NMe, a 9-aminomethyl SN-38 derivative, and IR following a single intraperitoneal dose of 40 mg/kg in mice. Additionally, ADMET properties were predicted using ADMETlab and SwissADME tools for comparison. Levels of NMe and irinotecan absorbed into plasma, distributed to tissues, and metabolized were monitored in liver, lung, spleen, kidney, and stool samples at 15, 30, and 60 min post-administration. Tissue extracts were analysed using high-performance liquid chromatography (HPLC), liquid chromatography–electrospray ionization quadrupole time-of-flight-tandem mass spectrometry (LC-ESI-QTOF-MS), and nuclear magnetic resonance (NMR) techniques after lyophilization and reconstitution. We compared the metabolomic profiles of irinotecan and NMe. Results: We identified and confirmed NMe-specific metabolites, including 9-CH₂-S-cysteine conjugate, 9-CH₂OH, and NMe-formyl. Notably, novel irinotecan metabolites (IR-OH and IR-ΔE) were detected in small amounts in kidney samples. In some cases, two literature-known photodegradation products of irinotecan were present. NMe was found to quickly metabolize with different distribution to tissues, significantly greater to kidney and liver. Two SN-38 glucuronides, SN-38G(α) and SN-38G(β), were detected corresponding to α- and β-anomers. Where it was possible, NMe, IR and SN-38 were quantified using external calibration curves. In IR group, controlled and prolonged release of SN-38 was confirmed in all samples, yet SN-38G was observed in minority only in plasma, kidney, or lungs. In NMe groups, great relative amounts of SN-38 and SN-38G were detected. Greater content of SN-38G in NMe group than in irinotecan is expected to contribute to modulation and alleviation of some side effects in irinotecan-involved therapies, such as gastrointestinal toxicities (GIT). Conclusions: NMe shows a distinct metabolic profile characterized by rapid biotransformation, higher systemic glucuronidation of SN-38, and formation of unique metabolites, suggesting a potentially wider therapeutic window and reduced toxicity compared with IR. Full article

Background/Objectives: Although copper nanoparticles (Cu-NPs) are increasingly explored as food and feed additives, there is still limited evidence on how the commonly consumed dietary fibre matrix modulates their effects on the gut microbiota. This study evaluated whether different dietary fibres (cellulose, pectin, inulin, psyllium) modulate Cu-NP–driven changes in caecal microbiota activity, composition, and bile acid metabolism in rats in a multifactorial design accounting for fibre type, copper dose, and copper form. Methods: Wistar male rats (n = 10 per group, 10 groups) were fed semi-purified diets for 6 weeks. Cu-NPs were provided at 6.5 or 13 mg Cu/kg diet and combined with cellulose (control fibre) or with pectin, inulin, or psyllium. Caecal digesta parameters, microbial enzyme activities, short-chain fatty acids (SCFAs), bile acids, and 16S rRNA sequencing were used to assess microbial diversity. Results: Final body weight did not differ among groups, whereas feed intake decreased most consistently with inulin and psyllium. Inulin and psyllium increased caecal digesta and tissue mass, while pectin increased caecal ammonia. Higher Cu-NPs dose reduced several microbial enzyme activities and lowered major SCFAs across most treatments; pectin most strongly preserved/enhanced glycosidase activities and was associated with increased SCFA levels vs. control, with a 32% rise in acetate, a 47% rise in propionate, and a 61% rise in butyrate. Fibre type dominated bile acid outcomes: psyllium reduced total bile acids by 11.8% vs. control, while inulin increased muricholic acids by 216% vs. control. Microbiota alpha and beta diversity separated primarily by fibre type, with distinct clustering particularly in pectin-fed groups. Across comparisons, Mucispirillum was consistently reduced in fibre-supplemented groups vs. cellulose, alongside recurrent changes in selected genera; functional profiling highlighted shared shifts in carbohydrate, fermentation, transport, and stress-response features under Cu-NPs exposure. Conclusions: The gastrointestinal and microbiota responses to Cu-NPs are strongly fibre-dependent; thus, Cu-NP safety and functionality should be evaluated together with the accompanying dietary fibre matrix, not as a standalone exposure. Implications for humans remain indirect and require confirmation in human-relevant models and clinical settings. Full article

Displacement estimation methods in strain elastography use ultrasound signals to estimate displacements and strain in soft tissue. Although several methods exist, systematic comparisons under controlled simulation conditions for lesions smaller than 5 mm are limited. Evaluating axial accuracy for superficial and intermediate depths in small breast cancer lesions is clinically important, as early-stage detection with existing techniques remains challenging. In this study, speckle tracking, the Doppler method, and the combined autocorrelation method (CAM) were used to estimate axial displacements from simulated elastography signals. The performance of these methods was assessed using the root mean square error (RMSE) for displacement field, strain, and tumor size estimation in a three-layer model comprising healthy tissue–tumor–healthy tissue. An extended analysis considering anatomically realistic tissue and motion artifacts conditions for the case of smallest lesion is presented. Finally, the CAM method, which obtained the best results, was assessed varying SNR/strain values. Simulation results show that CAM outperforms the other methods in displacement estimation across early-stage tumor sizes at both superficial and intermediate depths in all performed tests. Full article

Diagnostic imaging is essential in veterinary practice, and cone-beam computed tomography (CBCT) has emerged as a promising tool to complement radiography. This study aimed to optimize the image quality of a novel multimodality veterinary X-ray prototype integrating direct digital radiography, fluoroscopy and CBCT, and to assess its potential clinical applications, focusing on the CBCT component. The study was conducted in three phases: optimization of CBCT image quality using postmortem samples, comparison of CBCT and 16-slice multidetector CT (MDCT) images of four cadavers (two dogs and two cats), and potential clinical applications in 24 live patients. Comparative evaluation in postmortem scans revealed that CBCT achieved equal quality in 65% of bone compared to MDCT and a slightly inferior quality in 90% of soft-tissue structures using the bone reconstruction protocol, with beam hardening as the main limiting factor. Clinical validation showed that CBCT was particularly useful for identifying small fractures and mineralized structures, providing diagnostic information not clearly visible on radiographs. Integration of radiography, fluoroscopy, and CBCT in a single device facilitated workflow and allowed a more precise diagnosis in most of the patients examined with the prototype, which demonstrated promising diagnostic performance in small-animal and exotic veterinary practice. Full article

Background/Objectives: Locally advanced midface malignant tumors require extensive resection, resulting in complex defects involving bone and multiple soft tissue structures. Reconstructing these substantial defects presents a significant challenge to restore both function and aesthetics. This study aims to compare the functional and aesthetic outcomes of chimeric free flaps versus single free flaps in midface microvascular reconstructions. Methods: This retrospective analysis included fifty consecutive patients with Type III Cordeiro defects who underwent midface reconstruction with free tissue transfer between 2020 and 2024. The cohort included fourteen patients who received prefabricated chimeric flaps and thirty-six patients who received single free flaps. Outcomes were assessed six months postoperatively using a modified University of Washington Quality of Life Questionnaire (UW-QOL), analyzing domains including speech, chewing, sensation, appearance, pain, and social activity. Statistical analysis was performed using the Mann–Whitney U test. Results: In the chimeric flap group, no major flap necrosis or complications were observed. In unadjusted comparisons, the chimeric flap group showed higher transformed UW-QOL scores in several domains. Statistically significant between-group differences were observed for opening and speech (p = 0.004), change in appearance (p = 0.022), sensation (p = 0.011), and social activity (p = 0.006). Aesthetic outcomes, assessed via patient rating of appearance, were also significantly higher in unadjusted comparisons with the chimeric flap approach. Furthermore, in Type IIIa defects, titanium mesh successfully provided reliable orbital support. Conclusions: Chimeric free flaps represent a feasible reconstructive option in selected cases of complex maxillary and midface reconstruction. Their main advantages—providing the proper amount of specific, well-vascularized tissue and offering greater mobility of components— may be associated with more favorable functional, aesthetic, and social outcomes in unadjusted comparisons compared to reconstruction using single free flaps. Full article

Chest X-ray (CXR) imaging remains the most widely used radiological modality for assessing pulmonary and cardiothoracic disease, yet its interpretation is inherently constrained by tissue superposition, subtle radiographic findings and marked inter-observer variability. Recent advances in artificial intelligence (AI) have driven significant progress in automated CXR analysis, supported by large public datasets, evolving annotation strategies and increasingly expressive deep learning architectures. This review presents a comprehensive synthesis of approaches for pulmonary abnormality detection, encompassing convolutional neural networks, transformers, multimodal and vision–language models and self-supervised representation learning. We critically discuss their strengths, limitations and vulnerability to label noise, domain shift and shortcut learning. In parallel, we examine dataset properties, annotation practices, robustness challenges, explainability methods and the heterogeneity of evaluation protocols that hinder fair comparison and clinical translation. Building on these observations, the review identifies key future directions, including foundation models, multimodal integration, federated and domain-generalized training, longitudinal modeling, synthetic data generation and standardized clinical evaluation frameworks. By integrating methodological and clinical perspectives, this work offers an up-to-date reference for researchers and clinicians and outlines a roadmap toward reliable, interpretable and clinically deployable AI systems for chest radiography. Full article

Biocompatible thin films are essential for advancing biomedical devices, as they enhance integration with biological tissues, improve device longevity, and reduce complications. The rapid evolution of both medical needs and materials science has led to a diverse array of deposition techniques, each offering unique advantages and challenges for tailoring surface properties without compromising the bulk characteristics of implants and sensors. While laser-based methods—such as pulsed laser deposition (PLD) and Matrix-Assisted Pulsed Laser Evaporation (MAPLE)—are renowned for their precision, ability to preserve complex material stoichiometry, and suitability for low-temperature processing, the broader landscape includes several other important approaches. Physical Vapor Deposition (PVD) techniques, including magnetron sputtering and pulsed electron deposition, are widely used for their ability to create uniform, adherent coatings with controlled thickness and composition, making them suitable for both hard and soft biomedical substrates. Chemical Vapor Deposition (CVD) and its plasma-enhanced variant (PECVD) offer conformal coatings and excellent control over film chemistry, which is particularly valuable for functional polymer and ceramic films. Other methods, such as sol–gel processing, ion beam deposition, and electrophoretic deposition, provide additional flexibility in terms of coating composition, adhesion, and processing temperature, allowing for the fabrication of films with tailored mechanical, chemical, and biological properties. Despite these advances, the field faces ongoing challenges in optimizing film properties for specific clinical applications, ensuring reproducibility, and scaling up production for widespread use. The necessity of this review lies in its comprehensive comparison of laser-based techniques with alternative deposition methods, providing critical insights into their respective strengths, limitations, and suitability for different biomedical scenarios. By synthesizing recent developments and highlighting current gaps, this review aims to guide researchers and clinicians in selecting the most appropriate thin-film deposition strategies to meet the evolving demands of next-generation biomedical devices. Full article

Background: Prostate cancer (PCa) shows a marked biological heterogeneity that is closely associated with tumor aggressiveness. A substantial proportion of clinically significant tumors remain undetected by multiparametric magnetic resonance imaging (mpMRI). Elucidating the molecular basis of MRI visibility and identifying non-invasive biomarkers could improve the risk stratification and clinical management of patients. Accordingly, this study aimed to assess tissue and urine proteomic signatures associated with PCa aggressiveness and mpMRI visibility. Methods: In this exploratory study, we performed an integrated proteomic analysis of prostate tissue and preoperative urine samples from 24 patients stratified into four groups: benign prostatic hyperplasia (BPH), indolent PCa (Gleason 6), clinically significant PCa with MRI-visible lesions, and clinically significant PCa with MRI-non-visible lesions. Data-independent acquisition mass spectrometry (DIA workflows) was used to identify differentially expressed proteins associated with malignancy, tumor aggressiveness, and MRI visibility. Results: Pairwise proteomic analyses revealed significant molecular differences between BPH and all PCa groups, identifying 694 non-redundant proteins differentially expressed in tissue and 482 in preoperative urine, showing molecular features associated with both disease presence and progression. Comparative tissue and urine analyses identified 82 proteins, reflecting shared biological pathways in metabolism, cytoskeletal organization, immune processes, and extracellular matrix remodeling. Finally, a direct comparison of MRI-visible and MRI-non-visible clinically significant PCa identified a panel of differentially expressed proteins, including LCN2/NGAL, S100A9, and AOC1/DAO, that showed differential urinary abundance and prognostic relevance in the TCGA-PRAD cohort. Conclusions: Our results suggest that proteomic alterations in PCa are associated with disease progression and aggressiveness and capture biologically relevant differences between tissue and urinary proteomes. These differences are also observed between MRI-visible and MRI-non-visible clinically significant prostate cancers, supporting the potential of urinary proteomics as a non-invasive complement to imaging-based diagnostics. Full article

Background: Metalloproteinases (MMPs), together with their tissue inhibitors (TIMPs), regulate the extracellular matrix (ECM) in various tissues. MMP-2 and TIMP-2 maintain this process in renal tissue. An imbalance in the MMP-2/TIMP-2 ratio alters the abundance and proportions of specific extracellular matrix components, leading to kidney fibrosis. We aimed to assess differences in the morphometric parameters of the kidney and the immunohistochemical (IHC) expression of MMP-2 and TIMP-2 in kidney biopsies according to their fibrotic state. Methods: The histological slides were scanned using the 3DHISTECH Pannoramic MIDI II Scanner, and the resulting digital images of the sections were analyzed using Pattern Quant software; the morphometric analyses were performed with the Slide Viewer application. Results: In the current manuscript, we have investigated the significant enlargement of the diameter of the urinary space and renal corpuscle, as well as the reduced height of the epithelial lining of the proximal and distal convoluted tubules, of grafted kidneys with fibrosis when compared to the non-fibrotic kidneys. Moreover, we have noticed a rising MMP-2/TIMP-2 ratio in the immunohistochemical reaction in the renal tissue of fibrotic grafted kidneys in comparison to healthy kidneys. Conclusions: These results suggest that the MMP-2/TIMP-2 ratio, together with the lower inhibition of MMP-2, may promote an increased extracellular matrix remodeling, which accompanies the development of fibrosis. Full article