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PurposeMulticentric osteolysis nodulosis and arthropathy (MONA) syndrome is a rare autosomal recessive skeletal dysplasia. Caused by mutations in the matrix metalloproteinase 2 gene (MMP2) on chromosome 16q12, this syndrome has infrequently been associated with ophthalmic manifestations. Corneal opacities have been reported but not described or documented in detail.MethodsComplete ophthalmologic examination and multimodal anterior segment imaging were used to characterize the corneal findings in a patient with MONA syndrome.ResultsA 19-year-old with MONA syndrome was referred for an eye exam based upon MONA screening recommendations. Visually insignificant peripheral corneal opacities were noted. Anterior segment optical coherence tomography (AS-OCT) demonstrated posterior stromal and endothelial hyperreflectivity. Confocal microscopy demonstrated an acellular peripheral endothelium with a normal central endothelium.ConclusionsCorneal opacities can occur with MONA syndrome, which is caused by mutations in the MMP2 gene. In the patient presented here, the corneal opacities are peripheral, deep stromal, with sparing of the anterior stroma and epithelium.

Peyronie's disease (PD) presents a multifaceted challenge in contemporary urological practice, marked by penile deformity, pain, and the potential for erectile dysfunction. We meticulously explored the existing literature of intralesional/topical interventions, aiming to provide clinicians with a nuanced understanding of available options for comprehensive PD management. To conduct this review, we performed a systematic search using the PubMed, Scopus, and ScienceDirect databases, including the keywords of combination of the "Peyronie's disease/plastic induration of the penis (PIP) and intralesional/topical treatments". The study selection was based on adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, resulting in the inclusion of 16 articles. We delve into the effectiveness and safety profiles of collagenase Clostridium histolyticum (CCH), interferon, platelet-rich plasma (PRP), hyaluronic acid, botulinum toxin, stem cell, extracorporeal shock wave therapy (ESWT), and traction therapy, assessing their impact on penile curvature, length improvement, and patient-reported symptoms and outcomes. The best options evaluated are intralesional injections of CCH and penile traction devices, alone or in combination. Despite PD remains a challenge for urologists, the objective of this review is to contribute to the evolving landscape of PD management, fostering informed decision-making, and personalized care for individuals grappling with this challenging condition. [ABSTRACT FROM AUTHOR]

Minimally invasive treatments for Dupuytren's disease (DD), such as percutaneous needle fasciotomy (PNF) and collagenase clostridium histolyticum (CCH), have become alternatives to open surgeries. This meta-analysis compared these treatments in terms of complications, patient satisfaction, clinical outcomes, and recurrence. Relevant studies up to June 2024 were identified through major databases, following PRISMA guidelines, and the study was registered on PROSPERO. Statistical analysis using Review Manager 5.4 found PNF had lower post-operative rates of oedema (RR = 0.15, 95% CI [0.09, 0.27], p < 0.00001), lymphadenopathy (RR = 0.09, 95% CI [0.02, 0.38], p = 0.0010), and pruritus (RR = 0.1, 95% CI [0.01, 0.73], p = 0.02) compared to CCH. However, there were no significant differences in skin tears, recurrence, reintervention, extension deficit, or residual flexion at metacarpal and proximal interphalangeal joints (p > 0.05). Patient-reported outcomes, including QuickDASH and URAM scores, also showed no significant differences. Eleven studies involving 1443 patients were analysed, and most were at a low-to-moderate risk of bias, as assessed using the Cochrane or Newcastle–Ottawa tools. While PNF showed fewer minor complications, overall clinical and patient-reported outcomes were comparable between the treatments. These findings highlight the need to tailor treatment choices to patient preferences and clinical context. [ABSTRACT FROM AUTHOR]

Introduction: Cervical disc herniation (CDH) is the most common cause of cervical radiculopathy and causes persistent neck pain and neurological deficits. Collagenase chemonucleolysis has been successfully applied to treat lumbar disc herniation, which has a similar pathological mechanism to CDH. However, its application for CDH remains under-researched, and there is an even greater lack of high-quality clinical evidence. This study aims to evaluate the efficacy and safety of collagenase chemonucleolysis for treating CDH. Methods: Eligible patients with CDH underwent collagenase chemonucleolysis via anterior cervical intradiscal injection or epidural injection. The primary efficacy endpoint showed an excellent and good rate regarding the Odom criteria, which was not lower than the reference value (≥ 78%) at 6 months postoperatively. The secondary efficacy endpoints were the percentage reduction in Numeric Rating Scale (NRS) and Neck Disability Index (NDI) scores from baseline, which were not lower than the reference values (≥ 40%, ≥ 30%), and improvement in the 36-Item Short Form Health Survey (SF-36) score compared to the preoperative value. The pre- and postoperative CDH index of patients were also compared. Safety endpoints included the incidence of adverse events (AEs) and serious adverse events (SAEs). Results: An excellent and good rate regarding the Odom criteria 6 months postoperatively was 90.5% (133/147), which was significantly higher than 78% (P < 0.004, 95% confidence interval 85.7–95.2%). The reduction in NRS and NDI scores exceeded 40% (P < 0.001) and 30% (P < 0.001), respectively. The SF-36 scores at 3 months and 6 months postoperatively were significantly higher than those preoperatively (P < 0.001). A significant difference was observed in the pre- and postoperative CDH index (109.6 ± 119.1 vs. 70.8 ± 74.8, P < 0.001). The incidence of AEs was 22.5% (33/147), of which 97.8% were grade 1–2. No collagenase-related AEs and SAEs occurred. Conclusion: Collagenase chemonucleolysis treatment for CDH exhibited favorable efficacy and safety and may be a better choice for patients in whom conservative treatment is ineffective. Trial Registration: The trial was registered on www.Chictr.org.cn (ChiCTR2200063043). [ABSTRACT FROM AUTHOR]

Collagenase (MMP-1, -8, and -13) is one of the groups of the matrix metalloproteinases (MMPs) that is responsible for the breakdown of collagen, particularly type-I collagen, which is found in profusion in the extracellular matrix (ECM). It is essential to understand the role of a group of biomarkers in the progression of periodontal disease. This study aims to evaluate the expression of MMP-1, -8, and -13 combined in the periodontitis progression induced by wire ligation and Enterococcus faecalis inoculation using the rat model. Twelve rats were allocated uniformly between the control group 0-day, experimental group 7- and 14-days. Orthodontic wire (0.2 mm) was placed between the proximal space of the right upper first and second molar tooth area and 0.5 μl of 1.5 × 108 cfu/ ml. Rats in the experimental groups received an injection of E. faecalis suspension into their gingival sulcus. After the respective induction time, the rats were euthanised. Gingival tissue and maxillary jaw samples were obtained from all rats for quantitative real-time PCR and histological examination. The results showed a significant increase in mRNA expression within the tissue samples from the gingiva of MMP-1 (p < 0.05), -8 (p < 0.01), and -13 (p < 0.01) in 7 days as compared to the control. The MMP-8 expression levels were also significantly reduced (p < 0.05). Histological analysis showed a higher inflammatory cell infiltration and the presence of osteoclast in the 7 days, which was reduced in the 14 days. MMP-1, -8, and -13 levels were positively correlated with the presence of inflammatory cells. Therefore, identifying a group of collagenases might be a useful biomarker to detect the progression of periodontitis. [ABSTRACT FROM AUTHOR]

Background: Dupuytren's disease (DD) is a systemic connective tissue disorder of the palm, predominantly affecting men of Northern European or Caucasian origin over 55. In addition to conventional surgery, Dupuytren's contracture can be treated in a minimally invasive way by injecting bacterial collagenase into the cord. However, studies on the long-term success rate when compared to the gold standard, surgical limited fasciectomy, are limited. Methods: This monocentric retrospective study examined 35 patients who had been treated with bacterial collagenase for Dupuytren's contracture, conducting a long-term follow-up after an average of 5.7 years. The results were compared to a control group of 40 patients treated with surgical limited fasciectomy on average 5.5 years ago. Finger extension (Tubiana stage), strength, sensitivity, the effect of possible risk factors, and patient-reported outcome measures (PROMs) were compared between the two groups. Results: The long-term results after therapy for DD showed a significant reduction in the Tubiana stage for both groups (p < 0.001). Additionally, we observed a longer mean preintervention Tubiana stage and a better long-term improvement in the Tubiana stage for patients with limited fasciectomy when compared to the collagenase group. (both p < 0.001). Neither grip strength nor the pinch test showed significant differences when compared within each group or when comparing both groups. Both the treated and untreated fingers of patients with limited fasciectomy had a superior two-point discrimination (p < 0.001). For the URAM questionnaire, we observed a significantly better result in the control group (p < 0.01). Retrospectively, significantly more patients in the collagenase group would not choose the same therapy to treat DD (35 vs. 8%; p < 0.05). Conclusions: The two therapy options should be seen as complementary for the treatment of DD. Collagenase therapy seems a sensible option for DD with an earlier Tubiana stage and contractures that predominantly affect the MCP joint. Contractures with higher Tubiana stages that also affect the PIP joint should predominantly be treated with limited fasciectomy. [ABSTRACT FROM AUTHOR]

Background: Zanthoxylum piperitum (L.) DC., commonly known as Japanese pepper, is a deciduous shrub native to East Asia. Its berries are widely used as a spice, known for imparting a distinctive, tingly numbing sensation. Biologically, Z. piperitum has antimicrobial, antioxidant, and anti-inflammatory properties, and it is studied for its potential benefits in pain relief and digestive health. This study proposed a novel biotechnological Z. piperitum phytocomplex (ZPP) obtained by plant cell culture for skin health, specifically targeting collagen synthesis, extracellular matrix stability, and resilience against cellular stress. Given the bioactivity of Z. piperitum, we aimed to analyze its efficacy as a sustainable alternative for skin-supportive applications in cosmetics and supplements. Methods: ZPP was produced through stable plant cell cultures, yielding a lignan-rich (3.02% w/w) phytocomplex. Human fibroblasts (HFFs) were treated with varying ZPP concentrations to assess cellular viability, collagen metabolism, and ECM-related enzyme activities, both under normal and cell stress conditions. The in vivo assessment was performed by measuring biophysical skin parameters such as hydration, elasticity, and roughness in female volunteers for a period of six weeks. Results: In vitro, ZPP exhibited non-cytotoxicity at all concentrations tested. Under hyperosmotic stress, ZPP reduced cellular damage, suggesting enhanced resilience. ZPP upregulated lysyl oxidase (LOX) protein levels, critical for collagen cross-linking and ECM stability, with protective effects observed under oxidative/inflammatory conditions. Additionally, ZPP selectively inhibited collagenase, attenuating collagen breakdown, though antioxidant activity was modest. In vivo evaluation highlighted improved skin hydration, elasticity, and roughness. Conclusions: ZPP shows promise as a biotechnological agent for skin health, particularly in supporting collagen integrity, ECM stabilization, and cellular resilience under stress. While further studies are needed to explore its full efficacy, especially for aging and environmentally stressed skin, these findings highlight ZPP's potential as a new ingredient for cosmetic formulations aimed at skin care and the treatment of alterations caused by aging or environmental conditions. [ABSTRACT FROM AUTHOR]

Abstract Background There is a substantial need for ex vivo cartilage damage models to assess new emerging cartilage repair strategies. Ex vivo cartilage explant models have the advantages of achieving standardized and reproducible experimental conditions while maintaining the cells in their native tissue environment. This study aimed to establish a bovine cartilage damage model to evaluate the safety and efficacy of novel cartilage repair therapies. We hypothesized that combining transient exposure to matrix-degrading enzymes with mechanical loading on bovine cartilage would simulate cartilage damage. Methods Prior to mechanical load, bovine osteochondral plugs underwent a brief 5-minutes treatment with collagenase to induce mild cartilage damage by disrupting the collagen network. To induce a moderate cartilage damage, aggrecanase 1 and aggrecanase 2 were additionally applied to the cartilage for 40 min post-collagenase treatment to degrade aggrecan. Data was analyzed using ANOVA or the Friedman test. Results Observations revealed a statistically significant loss of sulphated glycosaminoglycan (sGAG) using both Collagenase Treatment (CT) and Collagenase and Aggrecanase Treatment (CAT), while chondrocytes viability was maintained. Both treatments resulted in a significantly elevated release of inflammation markers during the initial two days, including IL6 and nitric oxide. Collagenase treatment also significantly increased neo-epitopes of aggrecan compared to the untreated plugs at day 7, suggesting endogenous aggrecanase activation upon collagen network disruption. The additional effect of mechanical loading on cartilage degeneration was also explored in the CT group. Mildly damaged cartilage treated solely with collagenase could withstand 1 h per day of cyclical load, at 10-20% compression of cartilage thickness combined with interfacial shear at 25 degrees. However, higher compression levels (20-40% of cartilage thickness) with the same shear stress regimen led to a significant increase in surface chondrocyte death, with no evidence of TUNEL staining. Conclusions This study establishes a promising model for evaluating cartilage repair strategies, and screening anti-catabolic drugs, particularly overload-related cartilage damage.

Background: Oncolytic viruses are promising tools for immune stimulatory gene therapy of cancer, but their clinical effect on solid tumors have so far been limited. Transduction of the target tumor cells is limited by both extracellular matrix that blocks viral spread within the solid tumor tissue and electrostatic forces that inhibit virus from binding its entry receptor on the cell surface. The enzymes hyaluronidase and collagenase and the polycations diethylaminoethyl (DEAE)-dextran, branched Polyethylenimine (PEI) and protamine sulfate have previously shown potential to improve gene transfer in different forms of viral gene therapy, since they may help the virus to overcome these barriers. In this study, we compared the transduction-enhancing potential of these substances when used as vehicles for adenoviral transduction in solid tumor tissue. Methods: Subcutaneous tumors of pancreatic ductal adenocarcinoma were established in mice and treated with a mix of adenoviral vector Adf35(GFP-Luc) and either one of the selected vehicles. Transduction efficacy was determined by quantification of the viral transgene expression level using live imaging. Results: Addition of hyaluronidase tripled the transgene expression of Adf35(GFP-Luc) when compared to virus alone. No such positive effect was seen for the other tested vehicles. Conclusions: Out of the tested candidates, hyaluronidase showed the best potential to facilitate viral spread in tumor tissue and transduction of tumor cells. Therefore, hyaluronidase may be used as vehicle to improve clinical efficacy of oncolytic virotherapies.

Skin aging is classified according to intrinsic factors, such as genetic and metabolic processes, and extrinsic factors, such as stress and exposure to ultraviolet radiation. These factors activate enzymes in the skin, such as collagenase, elastase, and hyaluronidase (HAse), thereby promoting skin aging. In this study, we investigated the effects of a Korean edible seaweed extract on collagenase, elastase, and HAse, three extracellular matrix enzymes involved in the aging process. Brown and green seaweed extracts showed high collagenase inhibitory activity. Among these, Cladophora wrightiana var. minor exhibited the highest inhibitory activity. In elastase inhibitory activities of seaweed extracts, the brown seaweed extract showed the highest elastase inhibitory activities compared to other seaweed extracts. Padina gymnospora showed the highest inhibitory activity among tested seaweed extracts. Green seaweed extracts of C. wrightiana var. minor showed the highest inhibitory activity, followed by brown seaweed extract. The results of this study suggest that seaweed extract strongly inhibits collagenase, elastase, and HAse, which are responsible for skin aging and antiwrinkle effects.

Abstract Pancreatic ductal adenocarcinoma (PDAC), characterized by a dense extracellular matrix (ECM), presents significant therapeutic challenges due to its poor prognosis and high resistance to chemotherapy. Current chemodrugs and diagnostic agents largely fail to cross the barrier posed by the ECM, which severely limits the PDAC theranostics. This study introduces a novel theranostic strategy using thioether-hybridized hollow mesoporous organosilica nanoparticles (dsMNs) for the co-delivery of copper (Cu) and disulfiram (DSF), aiming to induce cuproptosis in PDAC cells. Our approach leverages the ECM-degrading enzyme collagenase, integrated with dsMNs, to enhance drug penetration by reducing matrix stiffness. Furthermore, the innovative use of a pancreatic cancer cell membrane coating on the nanoparticles enhances tumor targeting and stability (dsMCu-D@M-Co). The multifunctional platform not only facilitates deep drug penetration and triggers cuproptosis effectively but also utilizes the inherent properties of Cu to serve as a T1-weighted magnetic resonance imaging (MRI) contrast agent. In vitro and in vivo assessments demonstrate significant tumor size reduction in PDAC-bearing mice, highlighting the dual functionality of our platform in improving therapeutic efficacy and diagnostic precision. This integrated strategy represents a significant advancement in the management of PDAC, offering a promising new direction for overcoming one of the most lethal cancers. Graphical Abstract

Seaweed is a great source of biologically active metabolites which could prove interesting in cosmeceutical applications. In this study, seven Icelandic seaweed species (Ascophyllum nodosum, Alaria esculenta, Laminaria hyperborea, Laminaria digitata, Saccharina latissima, Palmaria palmata, and Schizymenia jonssonii) were screened for total polyphenol content, antioxidant properties, and inhibition of skin-degrading enzymes. Antioxidant assays included DPPH (2,2-diphenyl-1-picrylhydrazyl), reducing power, and ORAC (oxygen radical absorbance capacity). In most assays, A. nodosum extracts were the most active. A. nodosum extracts also showed the strongest inhibition of the skin-degrading enzymes elastase and collagenase at low concentrations, demonstrating its skin-protective qualities. To further investigate the activity, A. nodosum was subsequently extracted with solvents with increasing polarity into seven different extracts. Compared to other extracts, the extracts obtained by extraction with acetone and methanol showed the highest activity in all assays. Extracts obtained with room-temperature water and 85 °C water also demonstrated moderate to high activities. The outcomes of this study support the potential utilization of the brown seaweed A. nodosum as a source of natural ingredients in cosmeceuticals.

Introduction: Traditional Eastern medicine (TEM) is becoming increasingly more popular in highly developed Western countries as an alternative form of supporting health and body care. Many herbs used in this medical practice possess antioxidant, anti-inflammatory and immunomodulatory effects. The skin aging process may progress with age, when collagen and elastin fibers gradually decrease. Excessive exposure to UV radiation, resulting in an increase in the production of free radicals, leads to damage at the molecular level to numerous structures in the body including the acceleration of skin aging. Material and methods: The content of polyphenolic compounds (among others: phenolic acids and flavonoids), antioxidant potential (ABTS, DPPH and FRAP assays) as well as the influence on the activity of enzymes, collagenase and elastase, were determined in infusions obtained from Gynostemma pentaphyllum, Tinospora cordifolia, Astragalus membranaceus, Codonopsis pilosula, Asparagus racemosus and Ocimum sanctum. Results: The highest content of polyphenolic compounds and the strongest antioxidant properties were observed in the infusions obtained from the O. sanctum herb, while the greatest ability to inhibit collagenase and elastase was observed in the infusions obtained from the T. cordifolia leaves. Conclusions: Infusions from the O. sanctum herb and T. cordifolia leaves may have a potentially beneficial effect on the skin and may be used in anti-aging formulations.

Leather industry is traditionally characterized by the use of large amounts of chemical agents, some of which are toxic to human health and the environment. However, during the last years, many efforts have been made with the aim of successfully implement enzymes as agents for different leather production stages. The lipopeptides produced by the Bacillus spp. genus have excellent surfactants and antibacterial properties and may collaborate in the soaking stage of leather processing as well as in leather preservation. Moreover, Bacillus sp. proteases and lipopeptides can be co-produced in one culture medium, saving the production costs. In the present work, a screening of enzymatic activities was performed on 11 strains of the Bacillus sp. genus that have been isolated from samples of an artisan tannery from Salta, Argentina. In particular, the ability of B. amyloliquefaciens B65 to degrade α-type (nails, hair, wool) and β-type (feathers) keratin was demonstrated by scanning electron microscopy (SEM). The co-production of proteases, keratinases, glycosidases, and lipopeptides of this strain was conducted at 37 °C in mineral media supplemented with chicken feathers. In these nutrient-deficient media, the strain secreted amylases, pectinases, proteases, keratinases, and collagenases. A MALDI-TOF study also revealed that the strains secreted homologues of kurstakins, iturins, surfactins, and fengycines lipopeptides families. Therefore, B. amyloliquefaciens B65 presents great industrial potential applications, not only for tanneries but also for other industries such as pharmaceuticals, food, textiles, and detergents, among others. [ABSTRACT FROM AUTHOR]

Seaweed is a great source of biologically active metabolites which could prove interesting in cosmeceutical applications. In this study, seven Icelandic seaweed species (Ascophyllum nodosum, Alaria esculenta, Laminaria hyperborea, Laminaria digitata, Saccharina latissima, Palmaria palmata, and Schizymenia jonssonii) were screened for total polyphenol content, antioxidant properties, and inhibition of skin-degrading enzymes. Antioxidant assays included DPPH (2,2-diphenyl-1-picrylhydrazyl), reducing power, and ORAC (oxygen radical absorbance capacity). In most assays, A. nodosum extracts were the most active. A. nodosum extracts also showed the strongest inhibition of the skin-degrading enzymes elastase and collagenase at low concentrations, demonstrating its skin-protective qualities. To further investigate the activity, A. nodosum was subsequently extracted with solvents with increasing polarity into seven different extracts. Compared to other extracts, the extracts obtained by extraction with acetone and methanol showed the highest activity in all assays. Extracts obtained with room-temperature water and 85 °C water also demonstrated moderate to high activities. The outcomes of this study support the potential utilization of the brown seaweed A. nodosum as a source of natural ingredients in cosmeceuticals. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to evaluate the yield, viability, clinical safety, and efficacy of the stromal vascular fraction (SVF) separated with a new protocol with all clinical-grade drugs. Materials and Methods: SVF cells were isolated from lipoaspirate obtained from 13 participants aged from 30 to 56 years by using a new clinical protocol and the laboratory protocol. The cell yield, viability, morphology, mesenchymal stem cell (MSC) surface marker expression, and differentiation abilities of the SVF cells harvested from the two protocols were compared. Furthermore, three related clinical trials were conducted to verify the safety and efficiency of SVF cells isolated by the new clinical protocol. Results: There were no significant differences in the yield, viability, morphology, and differentiation potential of the SVFs isolated with the clinical protocol and laboratory protocol. Adipose-derived mesenchymal stem cell (ASC) surface marker expression, including that of CD14, CD31, CD44, CD90, CD105, and CD133, was consistent between the two protocols. Clinical trials have demonstrated the effectiveness of the SVF isolated with the new clinical protocol in improving skin grafting, promoting mechanical stretch-induced skin regeneration and improving facial skin texture. No complications occurred. Conclusion: SVF isolated by the new clinical protocol had a noninferior yield and viability to that of the SVF separated by the laboratory protocol. SVFs obtained by the new protocol can be safely and effectively applied to improve skin grafting, promote mechanical stretch-induced skin regeneration, and improve facial skin texture. Trial Registration: The trials were registered with the ClinicalTrials.gov (NCT03189628), the Chinese Clinical Trial Registry (ChiCTR2000039317), and the ClinicalTrials.gov (NCT02546882). All the three trials were not patient-funded trials. No Level Assigned: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Tumor malignancy highly depends on the stiffness of tumor matrix, which mainly consists of collagen. Despite the destruction of tumor matrix is conducive to tumor therapy, it causes the risk of tumor metastasis. Here, metal‐anesthetic network‐coated dormant collagenase‐producing Clostridium is constructed to simultaneously destruct tumor matrix and inhibit tumor metastasis. By metal‐phenolic complexation and π–π stacking interactions, a Fe3+‐propofol network is formed on bacterial surface. Coated dormant Clostridium can selectively germinate and rapidly proliferate in tumor sites due to the ability of carried Fe3+ ions to promote bacterial multiplication. Intratumoral colonization of Clostridium produces sufficient collagenases to degrade tumor collagen mesh and the loaded propofol restrains tumor metastasis by inhibiting tumor cell migration and invasion. Meanwhile, the delivered Fe3+ ions are reduced to the Fe2+ form by intracellular glutathione, thereby inducing potent Fenton reaction to trigger lipid peroxidation and ultimate ferroptosis of tumor cells. In addition to a satisfactory safety, a single intratumoral injection of coated dormant Clostridium not only effectively retards the growth of established large primary tumors, but also significantly suppresses distal lung metastasis in two different orthotopic tumor models. This work proposes a strategy to develop advanced therapeutics for malignant tumor treatment and metastasis prevention. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC), characterized by a dense extracellular matrix (ECM), presents significant therapeutic challenges due to its poor prognosis and high resistance to chemotherapy. Current chemodrugs and diagnostic agents largely fail to cross the barrier posed by the ECM, which severely limits the PDAC theranostics. This study introduces a novel theranostic strategy using thioether-hybridized hollow mesoporous organosilica nanoparticles (dsMNs) for the co-delivery of copper (Cu) and disulfiram (DSF), aiming to induce cuproptosis in PDAC cells. Our approach leverages the ECM-degrading enzyme collagenase, integrated with dsMNs, to enhance drug penetration by reducing matrix stiffness. Furthermore, the innovative use of a pancreatic cancer cell membrane coating on the nanoparticles enhances tumor targeting and stability (dsMCu-D@M-Co). The multifunctional platform not only facilitates deep drug penetration and triggers cuproptosis effectively but also utilizes the inherent properties of Cu to serve as a T1-weighted magnetic resonance imaging (MRI) contrast agent. In vitro and in vivo assessments demonstrate significant tumor size reduction in PDAC-bearing mice, highlighting the dual functionality of our platform in improving therapeutic efficacy and diagnostic precision. This integrated strategy represents a significant advancement in the management of PDAC, offering a promising new direction for overcoming one of the most lethal cancers. [ABSTRACT FROM AUTHOR]

Desmoplasia is a hallmark feature of pancreatic ductal adenocarcinoma (PDAC) that contributes significantly to treatment resistance. Approaches to enhance drug delivery into fibrotic PDAC tumors continue to be an important unmet need. In this study, we have engineered a tumor-colonizing E. coli-based agent that expresses both collagenase and hyaluronidase as a strategy to reduce desmoplasia and enhance the intratumoral perfusion of anticancer agents. Overall, we observed that the tandem expression of both these enzymes by tumor-colonizing E. coli resulted in the reduced presence of intratumoral collagen and hyaluronan, which likely contributed to the enhanced chemotherapeutic efficacy observed when used in combination. These results highlight the importance of combination treatments involving the depletion of desmoplastic components in PDAC before or during treatment. [ABSTRACT FROM AUTHOR]

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The Aloe vera plant has been widely used as a food ingredient, medicine and cosmetics. This research aims to test the gel and ethanol extract of Aloe vera leaves as an antioxidant and absorber of UV light in vitro, as well as predicting the interaction mechanism for ROS1 kinase and collagenase receptors in silico. The antioxidant activity test method was carried out in vitro using DPPH (1,1-Diphenyl-2-Picrylhydrazyl-Hydrazine) reagent. Activity as a UV light absorber is carried out by calculating the sun protected factor (SPF) value. The antiaging activity test was carried out by predicting the interaction mechanism of the ROS1 kinase and collagenase receptors in silico using several phenolic compounds that have been found in Aloe vera. The total phenolic content of Aloe vera ethanol extract was 379.136 ± 0.34 GAE/g sample, while that of Aloe vera gel was 0.0619 ± 0.04 GAE/g sample. Aloe vera ethanol extract showed moderate antioxidant activity with an IC50 of 101.9 µg/mL, and is able to absorb UV light at concentrations of 0.05% and 0.1% with ultra protection criteria. Several phenolic compounds found in Aloe vera plants showed high binding energy to ROS1 kinase and collagenase receptors. Isoquercitrin showed the highest binding energy to the ROS1 kinase receptor, while isovitexin showed the highest binding energy to the collagenase receptor. The conclusion of this research showed that Aloe vera leaves contain compounds that have potential as antioxidants and antiaging. [ABSTRACT FROM AUTHOR]

Background: Dupuytren's disease (DD) is a systemic connective tissue disorder of the palm. It particularly affects men of Northern European or Caucasian origin over the age of 55. In addition to the classical surgical therapy via limited fasciectomy, Dupuytren's contracture can also be treated minimally invasively. A relatively new treatment method is the use of collagenase injections (Xiapex) to reduce the contracture of the fingers. The data regarding the long-term success of this therapy are currently limited. Methods: In this monocentric retrospective study, we examined 35 patients who were treated with collagenase (Xiapex) for Dupuytren's contracture in the long fingers. Following the manufacturer's recommendations, the injection was administered intralesionally, and the cord was ruptured through the passive extension of the finger under local anesthesia with Mepivacain the following day. The clinical follow-up examination was conducted after an average of 5.7 years. The stages of Dupuytren's disease were documented using the Tubiana classification. Additionally, parameters of finger extension ability, differentiated by metacarpophalangeal (MCP), and proximal interphalangeal (PIP) joints, as well as patient-specific risk parameters, were evaluated Results: The long-term results of collagenase therapy after an average of 5.7 years showed a significant improvement in the contracture of the affected fingers. In the MCP joints, the flexion contracture decreased from 42° to 17° (p ≤ 0.001), and in the PIP joints, it decreased from 56° to 33° (p ≤ 0.001). The primary recurrence rate was 11% for the MCP joints and 19% for the PIP joints, respectively. The analysis of risk factors showed a significant risk for worse long-term outcomes in patients with diabetes and those with nicotine abuse. Conclusions: Collagenase therapy for Dupuytren's disease achieved significant long-term improvements in contracture in both MCP and PIP joints. In accordance with general risk factors for DD, patients with diabetes and those with nicotine abuse are at risk of worse long-term outcomes. Overall, it is a time-saving, low-risk, and straightforward technique for treating the disabling contracture component of this disease. [ABSTRACT FROM AUTHOR]

Skin aging has been defined to enclose both intrinsic and extrinsic aging. Phytochemicals are frequently used for developing skin care formulations and could protect the skin's epidermal and dermal layers, consisting mainly of elastin and collagen, from UV radiation. Berberine is an isoquinoline alkaloid and a biologically active component from plant sources. Our objective was to assess Berberine's anti-aging capabilities by conducting elastase and collagenase enzyme inhibition and kinetic studies and to also evaluating its antioxidant capacity with three different methods. Furthermore, heat stability, pH and sun protection factor (SPF) of the formulated cream containing 1.5% berberine was evaluated. The elastase and collagenase IC50 values of berberine were estimated to be 47.54 and, 22.16 µg/mL respectively. Berberine was determined as an un-competitive inhibitor of elastase and collagenase. It scavenged DPPH and ABTS free radicals with IC50 values of 66.81 and 180.5 µg/mL respectively. 210.387 mg/L of berberine was equivalent in reducing power of 176 mg/L of ascorbic acid. SPF and pH value of cream containing berberine was found to be 12.3 and 5.62 respectively. In conclusion, these findings suggest that Berberine is a promising candidate for use as an active ingredient in cosmeceuticals, offering a natural approach to enhance skin health and reduce the visible signs of aging. [ABSTRACT FROM AUTHOR]

Collagen is a popularly known elastic structural protein in the human body system, where it forms an integral part of support networks in the skin, hair, and nails. This study evaluated natural phenolic compounds from Chrysophyllum albidum aqueous fruit extract in silico as potential anticollagenase inhibitors. The phenolic compounds present in the extract include quercetin, caffeic acid, chlorogenic acid, kaempferol, apigenin, catechin, and gallic acid. Schrodinger Maestro (v12.8) was used to carry out the molecular docking procedure of the phenolic compounds with collagenase. QikProp (Schrodinger Maestro v12.8) and the AdmetSAR 2.0 database were also used to predict the ADME (Absorption, Distribution, Metabolism, and Excretion) and toxicity profiles, respectively. DFT analysis was conducted using Spartan10 software. Molecular docking results revealed that chlorogenic acid has the strongest binding affinity with collagenase (-9.367 kcal/mol) compared with other C. albidum phenolic compounds (caffeic acid: -8.114 kcal/mol; gallic acid: -7.200 kcal/mol; quercetin: -6.551 kcal/mol; kaempferol: -6.182 kcal/mol; apigenin: - 5.436 kcal/mol; catechin: -5.347 kcal/mol) and reference compounds such as resveratrol (-5.333 kcal/mol), Vitamin C (-9.296 kcal/mol), Vitamin E (-3.073 kcal/mol), ursolic acid (-2.144 kcal/mol) (except arbutin; -9.518 kcal/mol). Furthermore, chlorogenic acid displayed good moderation for ADME/tox parameters and binding free energy value (MMGBSA) as investigated. DFT analysis confirmed the stability and molecular reactivity of the compounds. This study identifies chlorogenic acid, a natural phenolic compound in C. albidum aqueous fruit part extract, as a potential lead for skin anti-aging remedies, subject to further investigation. [ABSTRACT FROM AUTHOR]

Chios mastic gum (CMG), the resin of Pistacia lentiscus var. Chia, is a product with great ethnopharmacological and economic significance. This study attempts to investigate, for the first time, the activity of CMG, its fractions and isolated compounds against specific enzymes, which play pivotal roles in the degradation of proteins contained in skin connective tissue. Initially, crude CMG was subjected to extraction, fractionation and isolation through different chromatographic techniques to obtain the acidic and neutral fraction of terpenes. Additionally, the characteristic and major active triterpene acids of CMG, masticadienonic and isomasticadienonic acids (MNA, IMNA) were isolated in pure form. All samples were analysed by means of High-Performance Thin-Layer Chromatography (HPTLC) with four distinct development systems to obtain their constituents' profile. Finally, samples were tested for their ability to inhibit the elastase and collagenase enzymes. According to our findings, for collagenase, a mixture of MNA and IMNA demonstrated the most potent activity with an IC50 value of 31.07 μg/mL, while for elastase CMG's acidic fraction provided the most promising results with an IC50 value of 17.30 μg/mL. Overall, these results attempt to fill the gap in scientific knowledge about the use of CMG and its constituents in skincare and cosmetic products. [ABSTRACT FROM AUTHOR]

Lumbar disc herniation (LDH) affects millions globally, with annual healthcare costs exceeding $100 billion in the United States alone, driving increasing interest in minimally invasive radiological interventions as treatment alternatives. This narrative review examines developments in collagenase chemonucleolysis for LDH, integrating a literature analysis with clinical experience. Key advancements include the transition from single-agent to combination therapies, exploration of diverse injection routes, and the progression from C-arm fluoroscopy to multi-slice CT guidance. The synergistic use of collagenase, oxygen-ozone, and anti-inflammatory analgesics has enhanced efficacy. Safety measures such as aspiration tests, contrast agent tests, and lidocaine tests implemented to mitigate procedural risks. However, challenges persist, including non-standardized dosages and potential complications arising from intradiscal injections. Future research should focus on establishing accreditation systems, refining patient selection criteria, optimizing drug dosages, and exploring advanced image-guided technologies. While chemonucleolysis offers advantages such as minimal invasiveness and cost-effectiveness, its complexity necessitates a multidisciplinary approach. Key findings demonstrate that combination therapy achieves superior outcomes compared to monotherapy, with long-term efficacy rates reaching 90% and 6-month success rates of 95%. Additionally, CT guidance has significantly improved procedural precision and safety compared to traditional fluoroscopy. This review provides insights for clinicians and researchers, highlighting the potential of chemonucleolysis in LDH management to ensure its safe and effective integration into mainstream treatment protocols.

We examined whether treatment utilization for Dupuytren's contracture varied with the presence of adverse socioeconomic determinants of health in the United States. After propensity score matching, the presence of adverse socioeconomic determinants of health was associated with decreased treatment utilization. [ABSTRACT FROM AUTHOR]

Dupuytren disease is a benign, progressive fibroproliferative disorder of the hands. To date, only one pharmacotherapy (clostridial collagenase) has been approved for use in Dupuytren disease. There is a great need for additional nonsurgical methods that can be used to either avoid the risks of invasive treatments or help minimize recurrence rates following treatment. A number of nonsurgical modalities have been discussed in the past and continue to appear in discussions among hand surgeons, despite highly variable and often poor or no long-term clinical data. This article reviews many of the pharmacotherapies discussed in the treatment of Dupuytren disease and novel therapies used in inflammation and fibrosis that offer potential treatment options.

Purpose: Dupuytren contracture is characterized by the formation of cords and nodules in the palm. Surgical release has historically been the definitive treatment. Collagenase clostridium histolyticum (CCH) has been used successfully as an alternative to surgery. The treatment of proximal interphalangeal (PIP) contractures is the most challenging. The purpose of this study was to evaluate CCH treatment for Dupuytren contracture of the PIP joint. Methods: A retrospective chart review was performed for CCH treatment of Dupuytren contracture at a single institution from January 2010 to April 2023. Data collected included pretreatment/posttreatment total flexion contracture and adverse events. Contractures were analyzed both by severity (high >40° and low 50% correction of contracture) were associated with low severity contractures at postmanipulation. There were 256 adverse events recorded (54.5%), including 187 skin tears (39.8%), 68 cases of lymphadenopathy (14.5%), and one injection site infection (0.2%). High severity and combined contractures were independently associated with an increased incidence of skin tears upon manipulation. Conclusions: Collagenase clostridium histolyticum treatment is effective for isolated or combined PIP joint contractures. Adverse events were associated with more severe contractures. Given the degree of improvement based on contracture severity, earlier intervention may provide better correction of contracture. Type of study/level of evidence: Therapeutic III.

Desiree Giselle Castelanich,1,2 Luis Alberto Parra Hernández,2 Maricarmen Chacín3 1Sociedad Argentina de Dermatología, Buenos Aires, Argentina; 2Sociedad Internacional de Rejuvenecimiento Facial No Quirúrgico (SIRF), Barranquilla, Colombia; 3Universidad Simón Bolívar. Facultad de Ciencias de la Salud, Centro de Investigaciones de Ciencias de la Vida (CICV), Barranquilla, ColombiaCorrespondence: Maricarmen Chacín, Email Maricarmen.chacing@unisimon.edu.coIntroduction: Epidermoid cysts (E.C.s), also known as sebaceous cysts, are benign asymptomatic subepidermal nodules filled with keratin material. These cysts originate from the follicular infundibulum, which when obstructed by keratin, results in cyst formation. Conventionally, E.C.s have been managed surgically with a high success rate and minimal complications. In this report, we present the successful resolution of an E.C. using a minimally invasive technique involving the intralesional injection of recombinant hydrolytic enzymes like hyaluronidase, collagenase, and lipase.Case Presentation: A 44-year-old woman with no significant medical history presented to the clinic with a mass on her right cheek that had been evolving for over 10 years. Skin and soft tissue ultrasound confirmed the presence of an E.C. of 9.3× 6.6 × 9.3 mm. Owing to the size and location of the cyst, a decision was made to infiltrate the lesion with recombinant enzymes. Remarkably, significant clinical improvement was observed on Day 21, and complete dissolution of the E.C. occurred 40 days after the initial intervention. Importantly, no recurrences were observed during the 4-year follow-up period.Conclusion: Intralesional administration of hydrolytic enzymes represents an innovative technique in the management of E.C.s. However, further controlled studies are required to determine the efficacy and safety of this procedure.Keywords: epidermoid cyst, hyaluronidase, lipase, collagenase, sebaceous cyst

Purpose: Controversy exists regarding the comparative efficacy of collagenase injection and percutaneous needle fasciotomy in the treatment of Dupuytren contracture. The randomized controlled trials (RCTs) that have compared the two treatment methods have reported results mostly implying similar treatment efficacy, durability, and complications. We aimed to review these RCTs regarding methodical quality and risk of bias. Methods: We searched PubMed and Cochrane Library databases up to May 2023. All RCTs comparing collagenase injection with needle fasciotomy were included. Eligible articles were reviewed by two researchers, of whom one was blinded to each article’s title, authors, year of publication, journal, and source of the studies. To assess methodical quality, we used the modified Jadad scale yielding a score of 0 (lowest quality) to 5 (highest quality). We assessed risk of bias with the Cochrane risk-of-bias tool (RoB 2). Results: Five studies were eligible, comprising 204 patients treated with collagenase injection and 209 patients treated with needle fasciotomy. The modified Jadad score ranged from 1 to 2 points in the five studies, and the overall risk of bias was high in all studies. Pretrial protocols could be retrieved for only two studies, revealing important discrepancies with the published articles. Conclusion: The published RCTs that have compared collagenase injection with needle fasciotomy in the treatment of Dupuytren contracture demonstrate a high risk of bias.

Objective: The goal of this systematic review was to identify the mechanisms associated with the enzymatic degradation of collagen and gelatin biomaterials and the possible associated flaws. Methods: Four databases (PubMed, B-On, Cochrane Library, and ResearchGate) were used for the bibliographic search of articles. The research question was formulated using the PCC method, (P): collagen or gelatin sponges, hydrogels, and scaffolds; concept (C): enzymatic degradation of collagen or gelatin sponges, hydrogels, and scaffolds; and context (C): effect of enzymatic action on degradation time of collagen or gelatin sponges, hydrogels, and scaffolds. The search was contextualized according to PRISMA recommendations. The identification and exclusion of evidence followed the PRISMA criteria, with specific inclusion and exclusion factors being stipulated for the selection of articles. The risk of bias assessment was performed using the QUIN Scale. Results: The initial search was composed of 13,830 articles after removing duplicates; 56 articles followed for the full-text reading; 45 were excluded; then, 11 articles were obtained, constituting the results of this systematic review. All studies evaluated the materials using gravimetric analysis, and collagenases were the proteases used for the degradation solution. The materials tested were as follows: human-like collagen (HLC) hydrogel with microbial transglutaminase (MTGase), gelatin sponges subjected to different types of crosslinking, and collagen scaffolds with different types of crosslinking. The period of analysis varied between 0.25 h and 35 days. It was possible to highlight the lack of uniformity in the protocols used, which varied largely, thus influencing the degradation times. The risk of bias was low in nine studies and medium in two studies. Conclusions: This systematic review identified a gap in the literature, highlighting the absence of in vitro studies using human saliva and a collagenase concentration close to the physiological levels to simulate oral dynamics. However, based on existing literature, the mechanisms associated with collagen enzymatic degradation in collagen and gelatin biomaterials were comprehensively understood, answering the first research question postulated. In response to the second research question, the main shortcomings identified in the laboratory evaluation of mechanisms associated with collagen enzymatic degradation in collagen and gelatin biomaterials included the lack of standardization in degradation test protocols; this limited inter-study comparisons, which increased heterogeneity. Additionally, variations in collagenase concentrations and types influenced collagen degradation rates, and inappropriate evaluation intervals hindered the identification of total degradation time.

The healthy skeletal muscle extracellular matrix (ECM) has several functions including providing structural integrity to myofibers, enabling lateral force transmission, and contributing to overall passive mechanical properties. In diseases such as Duchenne Muscular dystrophy, there is accumulation of ECM materials, primarily collagen, which results in fibrosis. Previous studies have shown that fibrotic muscle is often stiffer than healthy muscle, in part due to the increased number and altered architecture of collagen fibers within the ECM. This would imply that the fibrotic matrix is stiffer than the healthy matrix. However, while previous studies have attempted to quantify the extracellular contribution to passive stiffness in muscle, the outcomes are dependent on the type of method used. Thus, the goals of this study were to compare the stiffness of healthy and fibrotic muscle ECM and to demonstrate the efficacy of two methods for quantifying extracellular-based stiffness in muscle, namely decellularization and collagenase digestion. These methods have been demonstrated to remove the muscle fibers or ablate collagen fiber integrity, respectively, while maintaining the contents of the extracellular matrix. Using these methods in conjunction with mechanical testing on wildtype and D2.mdx mice, we found that a majority of passive stiffness in the diaphragm is dependent on the ECM, and the D2.mdx diaphragm ECM is resistant to digestion by bacterial collagenase. We propose that this resistance is due to the increased collagen cross-links and collagen packing density in the ECM of the D2.mdx diaphragm. Taken altogether, while we did not find increased stiffness of the fibrotic ECM, we did observe that the D2.mdx diaphragm conveyed resistance against collagenase digestion. These findings demonstrate how different methods for measuring ECM-based stiffness each have their own limitations and can produce different results.

The increasing incidence of dermatological diseases prompts the search for new natural methods of treatments, and lichens, with their special symbiotic structure, are a little-known and promising source of biologically active substances. Seven lichen species, Cladonia unicialis (L.) Weber ex F.H. Wigg. (Cladoniaceae), Evernia prunastri (L.) Ach. (Parmeliaceae), Hypogymnia physodes (L.) Nyl. (Parmaliaceae), Parmelia sulcata (Taylor) (Parmeliaceae), Physcia adscendens (Fr.) H. Olivier (Physciaceae), Pseudoevernia furfuracea (L.) Zopf (Parmeliaceae), and Xanthoria parietina (L.) Th. Fr. (Teloschistaceae), were used in our experiment. We identified different metabolites in the acetone extracts of all the lichen species. Based on the high-performance liquid chromatography analysis, the content of lichen substances in the extracts was evaluated. The impact of the individual lichen-specific reference substances, compared to the lichen extracts, on the viability of keratinocytes (HaCaT cell line) and fibroblasts (BJ cell line) and on the activity of selected skin-related enzymes was investigated. Our results revealed that only emodin anthrone at a concentration of 200 mg/L was cytotoxic to keratinocytes and fibroblasts in both cell viability assays. In turn, the C. uncialis extract was only cytotoxic to keratinocytes when used at the same concentration. The other tested treatments showed a positive effect on cell viability and no cytotoxicity or indeterminate cytotoxicity (shown in only one of the tests). Elastase and collagenase activities were inhibited by most of the lichen extracts. In turn, the individual lichen compounds (with the exception of evernic acid) generally had an undesirable stimulatory effect on hyaluronidase and collagenase activity. In addition, almost all the tested compounds and extracts showed anti-inflammatory activity. This suggests that some lichen compounds hold promise as potential ingredients in dermatological and skincare products, but their safety and efficacy require further study. The high cytotoxicity of emodin anthrone highlights its potential use in the treatment of hyperproliferative skin diseases such as psoriasis. [ABSTRACT FROM AUTHOR]

Background: Skin problems caused by oxidative stress lead to the activation of collagenase and tyrosinase enzymes, contributing to skin aging, discoloration, and infections. Equisetum ramosissimum and Moringa peregrina were assessed for their potential uses in treating various skin conditions. Objective: The present research aimed to investigate the positive effects of polyphenols in Equisetum ramosissimum and Moringa peregrina extracts as potential cosmetic products for the treatment of different skin conditions. Methods: Total phenolic and flavonoid contents, antioxidants, and anti-collagenase and anti-tyrosinase activities of plant extract mixtures (PEM) at different ratios of (M. peregrina: E. ramosissimum) were determined using standard procedures. Inhibitory effects of PEM against acne-causing Staphylococcus aureus (ATCC 29213) were evaluated using the diameter (cm) of the inhibition zone method. A cream formulation containing PEM was developed and characterized for stability and potential skin irritation in rats using standard procedures. Results: The PEM at a ratio of (2:1) showed the highest total phenolic and flavonoid content (150.15 ± 2.8 mg/g, equivalent to gallic acid, and 41.5 ± 1.2 mg/g, equivalent to quercetin, respectively). Antioxidant activities for PEM (2:1) were also optimal, as determined by the DPPH and ABTS methods (IC50 = 7.06 ± 0.12 µg/mL and 53.29 ± 3.3 µg/mL, respectively). Furthermore, PEM (2:1) exhibited superior inhibitory activities against collagenase and tyrosinase enzymes (IC50 = 32.4 ± 1.19 µg/mL and 8.4 ± 1.19 µg/mL, respectively). Antimicrobial activity of PEM (2:1) tested on S. aureus showed the largest zone of growth inhibition (2.8 cm) at a concentration of 60 mg/mL. Studies on the PEM (2:1) cream formulation revealed that it remained stable under room conditions. Skin irritation tests on rats showed no signs of oedema or erythema after treatment. Conclusion: The PEM with a ratio of (2:1) demonstrated optimal activity as an oxidative stress-neutralizing agent, inhibitor of enzymes responsible for skin aging and hyperpigmentation, and antibacterial agent. The cream formulation containing PEM exhibited physical stability and no detectable risk of skin irritation throughout the research procedures. [ABSTRACT FROM AUTHOR]

Purpose: Our goal was to identify new Peyronie's disease (PD) subtypes, non-PD penile curvature classifications, and define active (acute) vs stable (chronic) phases of disease using evidence-based analyses. Materials and Methods: A retrospective review was performed of 1098 men who presented with penile deformity, including subjective standardized and nonstandardized questionnaires and objective measures. A second cohort of 719 men who were sent a mailed survey was also utilized for the relapsing/remitting subtype. Statistical analyses were performed to identify clusters of disease characteristics representative of distinct PD and non-PD categorizations, including sensitivity/specificity analyses and subtype comparisons. Results: Comparative analyses identified 4 distinct subtypes of PD: (1) classical and nonclassical, (2) calcifying—moderate/severe calcification, (3) progressive—subjective worsening following disease onset, and (4) relapsing/remitting—reactivation following ≥ 6 months of stability. Additional, non-PD categorizations included congenital (lifelong), maturational (developed around puberty), and trauma induced. Statistical analyses demonstrated unique profiles among each category. Penile pain was not found to be a reliable predictor for disease progression or stability. Stable phase disease (historically "chronic") was variably defined by subtype: classical (≥3 months); progressive, calcifying, or trauma induced (≥12 months + ≥3 months stable OR ≥6 months stable). Similarly, PD subtypes may be assigned at ≥ 3 months following disease onset. A PTNM staging system is proposed to help communicate disease states, in which P = PD component (Ca—calcifying, Cl—classical, P—progressive, R—relapsing/remitting, U—undifferentiated), T = trauma component (0—absent, 1—present), N = non-PD component (C—congenital, M—maturational, U—undifferentiated), and M = mode (0—stable, 1—active); for example, PClT1N0M0 = stable classical PD with prior trauma. Conclusions: The current study provides an evidence-based proposal for the establishment of new PD subtypes and non-PD curvature categorizations as well as a standardized definition for active vs stable phases of disease. [ABSTRACT FROM AUTHOR]

Objective: The goal of this systematic review was to identify the mechanisms associated with the enzymatic degradation of collagen and gelatin biomaterials and the possible associated flaws. Methods: Four databases (PubMed, B-On, Cochrane Library, and ResearchGate) were used for the bibliographic search of articles. The research question was formulated using the PCC method, (P): collagen or gelatin sponges, hydrogels, and scaffolds; concept (C): enzymatic degradation of collagen or gelatin sponges, hydrogels, and scaffolds; and context (C): effect of enzymatic action on degradation time of collagen or gelatin sponges, hydrogels, and scaffolds. The search was contextualized according to PRISMA recommendations. The identification and exclusion of evidence followed the PRISMA criteria, with specific inclusion and exclusion factors being stipulated for the selection of articles. The risk of bias assessment was performed using the QUIN Scale. Results: The initial search was composed of 13,830 articles after removing duplicates; 56 articles followed for the full-text reading; 45 were excluded; then, 11 articles were obtained, constituting the results of this systematic review. All studies evaluated the materials using gravimetric analysis, and collagenases were the proteases used for the degradation solution. The materials tested were as follows: human-like collagen (HLC) hydrogel with microbial transglutaminase (MTGase), gelatin sponges subjected to different types of crosslinking, and collagen scaffolds with different types of crosslinking. The period of analysis varied between 0.25 h and 35 days. It was possible to highlight the lack of uniformity in the protocols used, which varied largely, thus influencing the degradation times. The risk of bias was low in nine studies and medium in two studies. Conclusions: This systematic review identified a gap in the literature, highlighting the absence of in vitro studies using human saliva and a collagenase concentration close to the physiological levels to simulate oral dynamics. However, based on existing literature, the mechanisms associated with collagen enzymatic degradation in collagen and gelatin biomaterials were comprehensively understood, answering the first research question postulated. In response to the second research question, the main shortcomings identified in the laboratory evaluation of mechanisms associated with collagen enzymatic degradation in collagen and gelatin biomaterials included the lack of standardization in degradation test protocols; this limited inter-study comparisons, which increased heterogeneity. Additionally, variations in collagenase concentrations and types influenced collagen degradation rates, and inappropriate evaluation intervals hindered the identification of total degradation time. [ABSTRACT FROM AUTHOR]

Objective: Primary cell isolation is essential for studying cellular behavior and disease mechanisms, with collagenase-mediated tissue dissociation playing a critical role in the process. However, the impact of collagenase treatment duration on the proteome of primary cells, particularly in breast cancer research, remains underexplored. This study aims to investigate the effects of collagenase II treatment duration on the proteomic profiles of primary breast cancer cells. Materials and Methods: Breast cancer tissues from patients diagnosed with infiltrating ductal carcinoma were treated with collagenase II for either 1 or 3 hours. Subsequent proteomic analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Identified proteins were subjected to bioinformatic analyses to determine the functional implications of the proteomic changes induced by the different treatment durations. Results: Bioinformatic analyses showed that 1-hour treatment predominantly affected proteins involved in cytoskeletal organization and cell adhesion, with significant enrichment in actin cytoskeleton dynamics and structural molecule activity. In contrast, 3-hour treatment led to significant metabolic reprogramming, with enhanced regulation of pathways involved in energy production, including the TCA cycle and glycolysis. Conclusion: This study reveals for the first time that, collagenase II treatment duration significantly alters the proteomic profile of primary breast cancer cells, with shorter durations affecting structural proteins and longer durations inducing metabolic changes. Optimizing treatment time is crucial for targeted proteomic studies. [ABSTRACT FROM AUTHOR]

We have analysed the in silico potential of bioactive peptides from cheese whey, the most relevant by-product from the dairy industry, to bind into the active site of collagenase and elastase. The peptides generated from the hydrolysis of bovine β-lactoglobulin with three proteases (trypsin, chymotrypsin, and subtilisin) were docked onto collagenase and elastase by molecular docking. The interaction models were ranked according to their free binding energy using molecular dynamics simulations, which showed that most complexes presented favourable interactions. Interactions with elastase had significantly lower binding energies than those with collagenase. Regarding the interaction site, it was found that four bioactive peptides were positioned in collagenase's active site, while six were found in elastase's active site. Among these, the most we have found one promising collagen-binding peptide produced by chymotrypsin and two for elastase, produced by subtilisin and chymotrypsin. These in silico results can be used as a tool for designing further experiments aiming at testing the in vitro potential of the peptides found in this work. [ABSTRACT FROM AUTHOR]

The number of patients with degenerative tendon disease affects millions of people both among athletes and the general population, causing significant socio-economic consequences. Despite the availability of various methods of conservative and surgical treatment, more than a third of patients experience constant pain. Objective. To study the indicators of the metabolism of connective tissue in animals with a model of degenerative damage to tendons against the background of the introduction of a culture of fibroblastic cell elements. Methods. Therefore, the development of methods for restoring the structure of tendons using cell cultures, in particular fibroblasts, will allow to optimize the course of reparative processes, reduce the risk of complications during surgical intervention and accelerate healing, and at the molecular level -- to improve the structure of collagen fibers. Laboratory studies of biochemical markers of a tendon with a degenerative-dystrophic lesion and against the background of the introduction of cell culture can help in the differential diagnosis of its extracellular matrix. Results. The experimental data obtained by us indicate the presence of differences in the biochemical markers of tendons with degenerative-dystrophic lesions in rats 7, 21, and 45 days after the introduction of culture of fibroblastic cell elements. However, 45 days after the introduction of the culture of fibroblast cell elements, the normalization of metabolic processes in the extracellular matrix of connective tissue occurs, namely, the activity of collagenase and the concentration of protein-bound hydroxyproline approaches normal values. This indicates the predominance of the synthetic phase over the catabolic one in collagen metabolism. Conclusions. In this context, the introduction of culture of fibroblastic cell elements, as an alternative anti-inflammatory method, may provide another potential opportunity in the treatment of chronic degenerative-dystrophic lesions of the Achilles tendon. [ABSTRACT FROM AUTHOR]

Objective: To characterize inflammatory and mechanical changes in the collagenase-induced OA (CIOA) model in rats. Design: Skeletally mature, 6-month-old Wistar rats received unilateral intraarticular injections of saline, 500 U or 1000 U of collagenase on days 0 and 2 of the study. Joint tissues were harvested on either day 4 or 70 to evaluate the acute and long-term changes. Blood biomarkers, gait asymmetry and mechanical hyperalgesia were assessed repeatedly up until day 70. Results: The intraarticular injection of collagenase triggered an increase in cartilage degeneration and bone resorption over time, particularly for 1000 U. Similarly, mild synovitis was observed on day 70 with an increased number of synovial lining cells, increased fibrosis, and infiltration of peripheral macrophages. Mechanistically, these findings were linked to a dose-related mechanical weakening of the anterior cruciate ligament (ACL), which caused persistent joint destabilization throughout the study. Furthermore, the collagenase injection triggered acute inflammation and swelling of the synovium on day 4 and an acute systemic inflammatory response with increased cytokine and peripheral blood immune cell levels. While mild synovitis persisted until day 70, the systemic inflammatory response returned to control levels after 8 days. Similarly, the observed acute changes in gait and mechanical hyperalgesia also returned to baseline after 21 days. Conclusion: By evaluating inflammatory and mechanical factors at different doses and timepoints, our characterization enables a more targeted study design and increases the clinical relevance of future studies involving the CIOA model.