Amount Of Collagen Research Articles

Therapeutic potential of hyaluronic acid hydrogel combined with bone marrow stem cells-conditioned medium on arthritic rats’ TMJs

Conditioned media (CM) is derived from mesenchymal stem cells (MSC) culture and contains biologically active components. CM is easy to handle and reduces inflammation while repairing injured joints. Combination therapy of the CM with cross-linked hyaluronic acid (HA) could ameliorate the beneficial effect of HA in treating degenerative changes of articulating surfaces associated with arthritic rats’ temporomandibular joints (TMJs). This study aimed to evaluate the therapeutic potential of HA hydrogel combined with bone marrow stem cells-conditioned medium (BMSCs-CM) on the articulating surfaces of TMJs associated with complete Freund’s adjuvant (CFA)-induced arthritis. Fifty female Sprague-Dawley rats were divided randomly into five equal groups. Rats of group I served as the negative controls and received intra-articular (IA) injections of 50 µl saline solution, whereas rats of group II were subjected to twice IA injections of 50 µg CFA in 50 µl; on day 1 of the experiment to induce persistent inflammation and on day 14 to induce arthritis. Rats of group III and IV were handled as group II and instead, they received an IA injection of 50 µl HA hydrogel and 50 µl of BMSCs-CM, respectively. Rats of group V were given combined IA injections of 50 µl HA hydrogel and BMSCs-CM. All rats were euthanized after the 4th week of inducing arthritis. The joints were processed for sectioning and histological staining using hematoxylin and eosin, Masson’s trichrome and toluidine blue special staining, and immunohistochemical staining for nuclear factor-kappa B (NF-κB). SPSS software was used to analyze the data and one-way analysis of variance followed by post-hoc Tukey statistical tests were used to test the statistical significance at 0.05 for alpha and 0.2 for beta. In the pooled BMSC-CM, 197.14 pg/ml of platelet-derived growth factor and 112.22 pg/ml of interleukin-10 were detected. Compared to TMJs of groups III and IV, TMJs of group V showed significant improvements (P = 0.001) in all parameters tested as the disc thickness was decreased (331.79 ± 0.73), the fibrocartilaginous layer was broadened (0.96 ± 0.04), and the amount of the trabecular bone was distinctive (19.35 ± 1.07). The mean values for the collagen amount were increased (12.29 ± 1.38) whereas the mean values for the NF-κB expression were decreased (0.62 ± 0.15). Combination therapy of HA hydrogel and BMSCs-CM is better than using HA hydrogel or BMSCs-CM, separately to repair degenerative changes in rats’ TMJs associated with CFA-induced arthritis.

Systematic Review on Working Mechanisms of Signaling Pathways in Fibrosis During Shockwave Therapy

Fibrosis is characterized by scarring and hardening of tissues and organs. It can affect every organ system, and so could result in organ failure due to the accumulation of extracellular matrix proteins. Previous studies suggest that mechanical forces (such as shockwave therapy, SWT) initiate a process of mechanotransduction and thus could regulate fibrosis. Nevertheless, it is largely unexamined which pathways are exactly involved in the application of SWT and can regulate fibrosis. The present article seeks to elucidate the underlying effect of SWT on fibrosis. Evidence shows that SWT activates macrophage activity, fibroblast activity, collagen amount and orientation and apoptosis, which ultimately lead to an adaptation of inflammation, proliferation, angiogenesis and apoptosis. The included articles reveal that other proteins and pathways can be activated depending on the energy levels and frequency of SWT. These findings demonstrate that SWT has beneficial effects on fibrosis by influencing the proteins and pathways. Based on these data, which highlights the underlying mechanisms, we can make preliminary conclusions about the treatment modalities of SWT in scar formation, such as the energy levels and frequencies that are necessary to prevent or treat fibrotic tissue.

Collagen Isolated from Human Adipose Tissue and Its Cellular Affinity.

The use of collagen in cell cultures promotes cell proliferation and differentiation, and it has been commercialized. In this study, we separated and purified collagen from adipose tissue discarded during liposuction and prepared collagen-coated dishes. After collagen was identified from human adipose tissue, type identification and quantification were performed using SDS-PAGE and FPLC. Collagen type I was used to coat culture dishes. Human skin fibroblasts and human adipose tissue-derived stem cells were seeded at a density of 2.5×105 cells/mL on prepared dishes at a collagen concentration of 3 mg/mL and cultured for 7 days. Cell viability was then measured and analyzed. The WST-1 assay was used to evaluate the results. The amount of collagen in 300 g of adipose tissue was 25.5 mg for type I, 41.4 mg for type III, 10.6 mg for type IV, 6.5 mg for type V, and 15 mg for type VI. The highest rates were observed for adipose stem cells cultured on human adipose tissue-derived collagen-coated dishes. In cell cultures, cell affinity was higher when cells and the substrate used were of the same origin, and affinity was stronger when the tissue of origin was the same.

Sex differences in the substrate of atrial fibrillation and the outcome of thoracoscopic ablation

Abstract Background Women with atrial fibrillation (AF) suffer more from AF symptoms, a lower quality of life, and have an enhanced risk of stroke. The AF recurrence after ablation is higher in women than in men. We hypothesize that sex specific differences in the atrial fibrotic substrate underlie these differences in clinical outcome. Here, we sought to characterize atrial fibrosis and fibrosis formation in the left atrial appendage (LAA) of women and men undergoing thoracoscopic ablation of AF. Methods We used the excised LAA of 30 female and 30 male patients with persistent AF undergoing thoracoscopic AF ablation. Patients were matched for age. In addition propensity score matching was also conducted for adjusting intermediary variables such as AF duration, Age ≥ 75, Body mass index (BMI), and CHA2DS2-VASc score ≥ 4. LAAs were stained with picrosirius red to quantify collagen and with vimentin for fibroblasts. Images were analyzed automatically (Image J version 1.50i) using color deconvolution to identify the area fraction of collagen and fibroblast. Results Women had similar age as men (66.4±7.76 vs 66.1 ±7.57, P= 0.85) but had a trend toward more cardiovascular risk factors [CHA2DS2-VASc score ≥ 4, (23.3 vs 6.7)%, P=0.07]. The total percentage of fibroblasts was larger in women 14.98 (9.79-24.95) % than men 13 (5.85-17.46) %, P=.018. In addition, in women fibroblasts were located more in epicardially and endocardially than in the interstitium.[women 8.18 (5.06-13.36) % vs men 6.49 (2.73-9.92) % , P=0.005].There was not a remarkable differences in total amount of collagen between the groups [women 16.03 (9.67-26.98) % vs men 15.50 (9.50-20.90) %, P=0.57 ], but there was a trend towards more epicardial and endocardial collagen in women than men [11.81(5.75-22.11)% vs 10.24 (6.06-15.10) % , P=0.06]. Conclusion We demonstrate more epicardial and endocardial fibroblasts in the LAA of women compared to men with persistent AF. There was similarly a trend towards more epicardia and endocardial but not interstitial collagen deposition. These findings may –at least in part- underlie sex specific differences in AF pathophysiology and ablation outcome.

Individual and combined effects of commercial glyphosate, atrazine and 2,4-D herbicides on the gerbil ventral prostate

Exposure to pesticides, individually or in a mixture, in drinking water is one of the main sources of human contamination, which causes adverse effects on the reproductive system. Our study aimed to investigate, the effects of a 90-day exposure to low concentrations of glyphosate (GLY), atrazine (ATZ), and 2,4-dichlorophenoxyacetic acid (2,4-D), in commercial formulations, on morphological, molecular, and hormonal parameters of the ventral prostate of gerbils (Meriones unguiculatus). The animals were exposed via drinking water to individual concentrations of GLY: 700 μg/L, ATZ: 3 μg/L, and 2,4-D: 70 μg/L, as well as to their mixture (MIX). Our findings showed an increase in prostatic complex relative weight in ATZ-exposed animals. Stereological and morphometric techniques indicated an increase in the percentage and thickness of muscular stroma, following an increase in the amount of collagen and reticular fibers in the MIX group. Histopathological analysis showed a decrease in the incidence of epithelial atrophy, subepithelial inflammation, and microacini in the MIX. On the other hand, ATZ-exposed animals showed an increase in hyperplasia and total prostatic intraepithelial neoplasia (PIN). The expression of caspase-3 decreased and estrogen receptor alpha (ERα) increased in the 2,4-D and MIX. Western blotting showed an increase in estrogen receptor beta (ERβ) expression in MIX-exposed animals. Testosterone levels decreased in animals from the GLY, ATZ and 2,4-D groups. Our findings provide evidence that individual or combined exposure to herbicides causes hormonal imbalance and morphological alterations, besides favoring the incidence of proliferative lesions in the prostate, predisposing the gland to more severe injuries.

Comparison of Secretome Dental Pulp Stem Cell And Mebo Ointment on The Amount of Fibroblast and Collagen In Superficial Dermal Burns

Secretome Dental Pulp Stem Cells have been proposed as a new alternative for wound burn. The aim of this study is to compare Secretome Dental Pulp Stem Cells and MEBO ointment against several fibroblasts and collagen in the healing process of superficial dermal burns. This study used a post-test only controlled group design by using 15 rats that were given superficial dermal burned wounds. Rats were divided into a negative control group of NaCl 0.9% (K1), a treatment group of MEBO (K2), and a treatment group of DPSCs-secretome (K3). Histopathology was done on the 5th, 14th, and 21st days post-induction wound burn. Network-prepared histopathology by colouring Messon Trichomes. Then, it was observed under a microscope with 200x magnification. Scoring in a way semi-qualitative for assessing fibroblasts and collagen. The total score of fibroblasts in the MEBO group was higher than the DPSCs-secretome group on day 5th. In comparison, the score for increasing the amount of collagen in the DPSCs-secretome group on days 5th and 14th was higher than the MEBO group. DPSCs-secretome has better effectiveness in increasing the amount of collagen but not better in increasing fibroblasts compared to MEBO.

Differential effects of macrophage subtype-specific cytokines on fibroblast proliferation and endothelial cell function in co-culture system.

Macrophages are involved in several critical activities associated with tissue repair and regeneration. Current approaches in regenerative medicine are focusing on leveraging the innate immune response to accelerate tissue regeneration and improve long-term healing outcomes. Of particular interest in this regard are the currently known, four main M2 macrophage subtypes: M2interleukin (IL)-4,IL-13, M2IC, M2IL-10, M2non-selective adenosine receptor agonists (NECA) (M2IL-4,IL-13 → M2NECA). In this study, rat bone marrow-derived macrophages (M0) were polarized to each of the four subtypes M2IL-4,IL-13 → M2NECA and cultured for 72 h in vitro. Luminex assay results highlighted increased production of tissue inhibitor of metalloproteinases-1 (TIMP-1) for M2IL-4,IL-13, higher amounts of transforming growth factor-beta 1 (TGF-β1) for M2IL-10, and elevated vascular endothelial growth factor A (VEGF-A) from M2NECA. Co-culture experiments performed with M2IL-10 macrophages and L929 fibroblasts highlighted the increased production of soluble collagen within the media as well as higher amounts of collagen in the extracellular matrix. Human umbilical vein endothelial cells (HUVECs) were co-cultured with M2NECA macrophages, which demonstrated an increase in intercellular adhesion molecule (ICAM) and platelet endothelial cell adhesion molecule (PECAM), as well as increased formation of endothelial tubes. The findings of this study emphasize a critical demand for further characterization and analyses of distinct M2 subtypes and careful selection of specific macrophage populations for regeneration of specific tissue types. The current, broad classification of "M2" may be sufficient in many general tissue engineering applications, but, as conditions are constantly in flux within the microenvironment in vivo, a higher degree of specificity and control over the initial M2 subtype could result in more consistent long-term outcomes where macrophages are utilized as part of an overall regenerative strategy.

Dual optical elastography detects -induced alterations in the biomechanical properties of skin scaffolds.

The skin's mechanical properties are tightly regulated. Various pathologies can affect skin stiffness, and understanding these changes is a focus in tissue engineering. Ex vivo skin scaffolds are a robust platform for evaluating the effects of various genetic and molecular interactions on the skin. Transforming growth factor-beta ( ) is a critical signaling molecule in the skin that can regulate the amount of collagen and elastin in the skin and, consequently, its mechanical properties. This study investigates the biomechanical properties of bio-engineered skin scaffolds, focusing on the influence of , a signaling molecule with diverse cellular functions. The receptor I inhibitor, galunisertib, was employed to assess the mechanical changes resulting from dysregulation of . Skin scaffold samples, grouped into three categories (control, -treated, and + galunisertib-treated), were prepared in two distinct culture media-one with aprotinin (AP) and another without. Two optical elastography techniques, namely wave-based optical coherence elastography (OCE) and Brillouin microscopy, were utilized to quantify the biomechanical properties of the tissues. Results showed significantly higher wave speed (with AP, ; without AP, ) and Brillouin frequency shift (with AP, ; without AP, ) in -treated group compared with the control group. The difference in wave speed between the control and + galunisertib with ( ) and without AP ( ) was not significant. Moreover, the + galunisertib-treated group exhibited lower wave speed without and with AP and reduced Brillouin frequency shift than the -treated group without AP, further strengthening the potential role of in regulating the mechanical properties of the samples. These findings offer valuable insights into -induced biomechanical alterations in bio-engineered skin scaffolds, highlighting the potential of OCE and Brillouin microscopy in the development of targeted therapies in conditions involving abnormal tissue remodeling and fibrosis.

Dissociated urethral plate Onlay and standard Onlay urethroplasty for mid-distal hypospadias: A comparative study

BackgroundUrethral plate(UP) reserved Onlay urethroplasty currently had been widely used in mid-distal hypospadias. However, for children with 15-30° bending after degloving, only dorsal tunica albuginea plication was performed to correct penile ventral curvature(VC), and long-term follow-up showed a high recurrence rate of penile curvature. We developed a modified Onlay urethroplasty which dissociated the UP and completely removed the tissue beneath UP to fully correct penile curvature, and compared it with the standard Onlay urethroplasty to explore its rationality and feasibility. MethodsWe prospectively collected clinical data from 68 children with hypospadias who underwent standard or modified Onlay urethroplasty between September 2019 and June 2021, and evaluated interim outcomes to identify the complications between two groups. And we conducted histological examination of the tissue beneath the UP. ResultsA total of thirty-two patients underwent modified Onlay urethroplasty. Intraoperative curvature measurements showed that 37.5% (12/32) of patients had completely straightened their penis after dissecting UP and removing fibrous tissue beneath it. A total of thirty-six patients underwent standard Onlay urethroplasty. Totally five fistulas were reported in the first and second groups, respecitively as well as the complication rates were 15.6% and 13.9%, respectively (P > 0.05). The histological results showed that the tissue below the UP contains a large amount of collagen, mainly type I collagen. ConclusionThe dissociated UP Onlay urethroplasty can maximally remove factors limiting penis growth and completely correct penile curvature, without increasing the incidence of postoperative complications.Therefore, we recommend the application of improved Onlay urethroplasty in children with mid-distal hypospadias.

A review on the processing technique, physicochemical, and bioactive properties of marine collagen.

Collagens are conventionally derived from bovine and porcine sources. However, these sources were commonly associated with infectious diseases such as bovine spongiform encephalopathy, foot and mouth disease, autoimmune and allergic reactions, and religious constraints. The significant amount of collagen available in marine species, especially fish skins, scales, fins, and bones, shows that marine species can be a potential alternative source to mammalian collagen. Therefore, this review aims to give a clearer outlook on the processing techniques of marine collagen and its physicochemical and bioactive properties as a potential alternative to mammalian collagen. The two most suitable extraction methods for marine collagen are pepsin-soluble extraction and ultrasound-assisted extraction. Additionally, marine collagen's physicochemical and bioactive properties, such as antioxidants, wound healing, tissue engineering, and cosmetic biomaterial have been thoroughly discussed in this review. PRACTICAL APPLICATION: Collagen extracted from marine sources showed its potential in physicochemical and bioactive properties, including antioxidants and wound-healing capabilities, as an alternative to mammalian collagen. The significant amount of collagen found in marine species, particularly in fish skins, scales, bones, and sea cucumbers, suggests that marine sources could be a viable alternative to land mammal collagen due to their abundance and accessibility. The ultrasound-assisted extraction technique has improved the extracted marine collagen's physicochemical and bioactivity properties and quality properties.

Unravelling the impact of active and passive contributors to arterial stiffness in male mice and their role in vascular aging

Arterial stiffness, a key indicator of vascular health, encompassing active (vascular tone) and passive (extracellular matrix) components. This study aims to address how these different components affect arterial stiffness along the aorta and the influence of aging. Aortic segments of 12 week and 24 month old (both n = 6) male C57BL/6J mice were mounted in a Rodent Oscillatory Set-up to study Arterial Compliance, in order to measure arterial stiffness and vascular reactivity. Regional variations in arterial stiffness were evident, with abdominal infrarenal aorta (AIA) exhibiting highest stiffness and smallest diameters. AIA displayed both the highest amount of collagen and collagen:elastin ratio. Regional ex vivo vascular reactivity revealed heightened AIA contractions and lowered NO availability. Aging is a significant factor contributing towards vessel remodelling and arterial stiffness. Aging increased arterial stiffness, aortic diameters, collagen content, and reduced VSMC contraction. The results of this study could identify specific regions or mechanisms to target in the development of innovative therapeutic interventions aimed at enhancing overall vascular health.

Novel Collagen-Based Emulsions Embedded with Palmarosa Essential Oil, and Chamomile and Calendula Tinctures, for Skin-Friendly Textile Materials.

Skin-friendly textile materials were obtained by applying oil-in-water emulsions based on palmarosa essential oil, chamomile, and calendula tinctures onto cotton fabrics. Different formulations based on these bioactive principles incorporated in collagen as polymeric matrices were prepared and immobilized on a plain weave textile structure from 100% cotton. The functionalized textile materials were characterized in terms of physicochemical, mechanical, antibacterial, and biocompatibility points of view. The pH values of the prepared emulsions were in the range of 4.81-5.23 and showed no significant differences after 4 h of storage. Moreover, the addition of a higher quantity of active principles (palmarosa essential oil and plant tinctures) caused slightly lower values of acidic pH. The electrical conductivity of the obtained emulsions increased with the decrease in the oil phases in the system. The highest values were obtained for the emulsion developed with the smallest volume fraction of active principle-palmarosa essential oil and plant tinctures. The emulsion that contained the least amount of collagen and the highest number of active principles exhibited the lowest stability. The textile materials treated with synthesized emulsions exerted antibacterial effects against S. aureus and E. coli strains and did not affect keratinocyte growth, spreading, and organization, highlighting the biocompatibility of these developed skin-friendly textiles.

Review of the slaughter wastes and the meat by-products recycling opportunities

In the ancient times, the Kazakhstan population were considered as nomadic people, where a cult of all types of cattle breeding had a leading position. However, currently the processing approaches of livestock slaughter wastes and secondary meat raw materials are weakly developed. The presented review of waste-free technologies considers the utilization processes of following: carcasses, skins, bones, meat scraps, blood, adipose tissue, horns, feet, hooves, and internal organs. These substances are an important source of animal protein, collagen, bioactive peptides, blood plasma, minerals, and fats that can be applied in various industries: food, feed, medical, and technological. When slaughtering livestock, meat on bones makes up almost half of the total weight of livestock, yet the remaining half contains offal and inedible raw materials. Blood consists of: erythrocytes, leukocytes, platelets, and plasma. Animal bones have mostly proteins (30–50%) and lipids (13–20%) from bone tissues. Tendons, bones and skins contain a large amount of collagen. Animal fat and adipose tissue have 54.9% saturated acids, 40.9% unsaturated fatty acids and 4.2% polyunsaturated fatty acids. Bioactive peptides from collagen derivatives contain from 2 to 20 amino acids and have various biological (antihypertensive, antioxidant, and antimicrobial) activity. This review considers a world current status, modern prospects and opportunities in the slaughter wastes and the meat by-products recycling technologies. Overview of existing approaches for waste processing with the subsequent use of the final product in the food industry, the production of feed, medicines and technical products is considered. The complete processing within the slaughtering livestock and the secondary meat raw materials allows to expand the wide-range products with a low prime cost, thereby promoting to the sustainable development of agroecology by applying the waste hierarchy: Reducing, Reusing, and Recycling.

Coingestion of Collagen With Whey Protein Prevents Postexercise Decline in Plasma Glycine Availability in Recreationally Active Men.

Whey protein ingestion during recovery from exercise increases myofibrillar but not muscle connective protein synthesis rates. It has been speculated that whey protein does not provide sufficient glycine to maximize postexercise muscle connective protein synthesis rates. In the present study, we assessed the impact of coingesting different amounts of collagen with whey protein as a nutritional strategy to increase plasma glycine availability during recovery from exercise. In a randomized, double-blind, crossover design, 14 recreationally active men (age: 26 ± 5years; body mass index: 23.8 ± 2.1kg·m-2) ingested in total 30g protein, provided as whey protein with 0g (WHEY), 5g (WC05); 10g (WC10), and 15g (WC15) of collagen protein immediately after a single bout of resistance exercise. Blood samples were collected frequently over 6hr of postexercise recovery to assess postprandial plasma amino acid kinetics and availability. Protein ingestion strongly increased plasma amino acid concentrations (p < .001) with no differences in plasma total amino acid availability between treatments (p > .05). The postprandial rise in plasma leucine and essential amino acid availability was greater in WHEY compared with the WC10 and WC15 treatments (p < .05). Plasma glycine and nonessential amino acid concentrations declined following whey protein ingestion but increased following collagen coingestion (p < .05). Postprandial plasma glycine availability averaged -8.9 ± 5.8, 9.2 ± 3.7, 23.1 ± 6.5, and 39.8 ± 11.0mmol·360min/L in WHEY, WC05, WC10, and WC15, respectively (incremental area under curve values, p < .05). Coingestion of a small amount of collagen (5g) with whey protein (25g) is sufficient to prevent the decline in plasma glycine availability during recovery from lower body resistance-type exercise in recreationally active men.

The Potential Of Superoxide Dismutase Enzyme From Tomato Fruit (Solanum Lycopersicum) To Repair Collagen Damage In 3t3 Fibroblast Cells Exposed To Ultraviolet A Radiation

UV A radiation can cause photoaging to the skin which is show by a decrease in the amount of collagen and death of fibroblast cell. This study aimed to determine the SOD enzyme activity of tomatoes (Solanum lycopersycum Mill.) influences the increase of viability of fibroblast cell and deposition of collagen. The study design used a completely randomized design (CRD) with 11 treatments and 3 repetitions. The procedures of this study include: (1) extracting SOD enzymes (2) making bradford reagents (3) making standard protein solutions (4) measuring total protein content (5) testing the antioxidant activity of SOD enzymes (6) preparing 3T3 fibroblast cells (7) Cell exposure 3T3 fibroblasts with UV A rays (8) preparation of tomato SOD enzyme stock solutions (9) determination of cell viability and collagen deposition. Data analized by normality test, homogeneity test, one way ANOVA test, tuckey test and dunnet test. The results of SOD enzyme activity showed the highest percent inhibition was 77.83%. Highest value of percent viability of fibroblast cells that were exposed to UV A rays after given 90% SOD enzyme treatment was 233.00% and collagen deposition was 157.67%. The results showed that variations in the SOD enzyme concentration of tomatoes had a significant effect on cell viability and collagen deposition in fibroblast cells. with a value of sig = 0,000 (p &lt;α). Based on the result, we can concluded that SOD enzyme from tomatoe fruit show significant activity as anti-photoaging.

Lung decellularized matrix-derived 3D spheroids: Exploring silicosis through the impact of the Nrf2/Bax pathway on myofibroblast dynamics

Silicosis is an occupational respiratory disease caused by long-term inhalation of high concentrations of free silica particles. Studies suggest that oxidative stress is a crucial initiator of silicosis fibrosis, and previous studies have linked the antioxidative stress transcription factor known as Nrf2 to fibrosis antagonism. Myofibroblasts play a pivotal role in tissue damage repair due to oxidative stress. Unlike physiological repair, myofibroblasts in fibrosis exhibit an apoptosis-resistant phenotype, continuously synthesising and secreting significant amounts of collagen and other extracellular matrices, which could be a direct cause of silicosis fibrosis. However, the relationship and mechanism of action between oxidative stress and myofibroblast apoptosis resistance remain unclear. In this study, a new 3D cell culture model using mice lung decellularised matrix particles and fibroblasts was developed, simulating the changes in myofibroblasts during the development of silicotic nodules. Western Blot results indicate that silica stimulation leads to increased collagen deposition and decreased apoptosis-related protein Bax and oxidative stress-related protein Nrf2 in the 3D spheroid model. Immunofluorescence experiments reveal co-localisation in their expression. In Nrf2 overexpressing spheroids, Bax exhibits significant upregulation. In the Nrf2 knockout spheroids, Bax is also significantly downregulated; after intervention with Bax inhibitors, a significant downregulation of Bax-induced apoptosis was also detected in the Nrf2-overexpressed spheroids. In contrast, Bax-induced apoptosis showed a significant upregulation trend in Nrf2-overexpressed spheroids after intervention with Bax agonists. The results demonstrate that the spheroid model can mimic the development process of silicotic nodules, and silica stimulation leads to an apoptosis-resistant phenotype in myofibroblasts in the model, acting through the Nrf2/Bax pathway. This research establishes a new methodology for silicosis study, identifies therapeutic targets for silicosis, and opens new avenues for studying the mechanisms of silicosis fibrosis.

Biochemical and Histological Differences between Longitudinal and Vertical Fibres of Dupuytren's Palmar Aponeurosis and Innovative Clinical Implications.

Dupuytren's disease, a chronic and progressive fibroproliferative lesion of the hand, which affects the palmar fascia, has a recurrence rate after selective aponeurotomy of 20-40% at 5 years. This study focused, for the first time, on the microanatomical and histopathological characteristics of the longitudinal and vertical fibres (usually spared during surgery) in the aponeurosis with Dupuytren's disease, in different stages of the Tubiana's classification. Twelve human samples were collected and analysed by immunostaining, Total Collagen Assay, ELISA Immunoassay, and immunoblotting for the Von Willebrand factor, α-Sma, D2-40, CD-68, Total Collagen, Collagen-I and III, IL1β, TNF-α to analyse the blood and lymphatic vascularization, the amount and distribution of collagen, and the inflammation. The results show a progressive increase in the arterial vascularization in the vertical fibres (from 8.8/mm2 in the early stage to 21.4/mm2 in stage 3/4), and a parallel progressive decrease in the lymphatic drainage (from 6.2/mm2 to 2.8/mm2), correlated with a local inflammatory context (increase in IL-1β and TNF-α until the stage 2) in both the longitudinal and vertical fibres. The acute inflammation after stage 2 decreased, in favour of a fibrotic action, with the clear synthesis of new collagen (up to ~83 µg/mg), especially Collagen-I. These results clearly demonstrate the involvement of the septa of Legueu and Juvara in the disease pathology and the modifications with the disease's progression. A greater understanding of the pathology becomes fundamental for staging and the adequate therapeutic timing, to obtain the best morpho-functional result and the lowest risk of complications.

Evaluation of the effects of decellularized umbilical cord Wharton's Jelly ECM on polyhydroxy butyrate electrospun scaffolds: A new strategy for cartilage tissue engineering

The field of regenerative medicine has recently witnessed the emergence of the allogeneic decellularized extracellular matrix as a scaffold with natural biological signals in tissue engineering. In the present study, to prevent immune rejection and disease transmission, Wharton's Jelly extracellular matrix (WJM) derived from the human umbilical cord was first decellularized (DWJM). Eventually, the fibrous scaffolds based on poly 3-hydroxybutyrate (PHB) and five different concentrations (0, 1, 3, 5, and 10 wt%) of DWJM were fabricated through electrospinning. The results demonstrate reducing the diameter of the fibers, improved mechanical properties, hydrophilicity, and degradation rate in the scaffold containing 3 wt % DWJM. Excellent biocompatibility and increased chondrocyte cell adherence rate on the substrate of PHB-DWJM 3 % scaffolds compared with pure PHB scaffolds can be attributed to the high amounts of Collagen, sulfated glycosaminoglycans (GAGs), and hyaluronic acid (HA) in the DWJM. In conclusion, the physicochemical properties and biological activities of PHB-DWJM scaffolds indicate that blending DWJM with PHB electrospun scaffold can provide a suitable environment for articular cartilage tissue regeneration.

Diagnostic and prognostic significance of keloid-like collagen remodeling patterns in the extracellular matrix of colorectal cancer.

The desmoplastic reaction is considered a promising prognostic parameter for colorectal cancer. However, intermediate desmoplastic reaction is characterized by sizeable stromal heterogeneity, including both small amounts of keloid-like collagen (KC) in the fibrotic stroma and thick tufts of KC circumferentially surrounding cancer nests and occupying most of the fields of view. The present study aimed to evaluate the diagnostic and prognostic significance of KC histophenotyping with a quantitative visual assessment of its presence in the stroma of the invasive margin of TNM (The "tumor-node-metastasis" classification) stage II/III colorectal cancer (CRC). 175 resected tumors from patients with TNM stage II/III CRC were examined. Keloid-like collagen was assessed according to Ueno H. criteria. KC was assessed at the primary tumor invasive margin using Hematoxylin & Eosin and Masson's trichrome staining. The cut-off point for KC was examined using "the best cutoff approach by log-rank test." Using a cutoff point of 30%, we histologically divided fibrous stroma in the invasive area into two groups: "type A"-KC ≤ 0.3 and "type B"-KC>0.3. Type A stroma was observed in 48% of patients, type B-in 52%. The association between collagen amount and 5-year recurrence-free survival (5-RFS) was assessed using Cox regression analysis. Kaplan-Meier analysis and log-rank tests were used to assess the significance of survival analysis. Analysis of categorical variables showed that increased KC in CRC stroma predicted adverse outcomes for 5-RFS (hazard ratio [HR] = 3.143, 95%, confidence interval [CI] = 1.643-6.012, p = 0.001). Moreover, in Kaplan-Meier analysis, the log-rank test showed that type B exhibited worse 5-RFS than type A (p = 0.000). KC is an independent predictor of 5-year overall and RFS in patients with TNM stage II/III CRC treated with surgery, with worse survival rates when the amount of KC increases by >30%.

Characterization of Immune Cell Infiltration and Collagen Type III Disorganization in Human Secondary Lymphedema: A Case-control Study.

Secondary lymphedema (SL) affects 120 million people globally, posing a lifelong burden for up to 37% of cancer survivors. Chronic inflammation and progressive fibrosis are key drivers of SL, yet detailed characterization of immune cell subpopulations across lymphedema stages is lacking. This study aimed to investigate the immunologic profile of lymphedematous skin and its association with extracellular matrix changes, which could serve as clinical biomarkers or therapeutic targets. This case-control study analyzed the skin from 36 patients with and without SL, using immunofluorescence to quantify T cells, B cells, macrophages, and their subpopulations. Collagen quantity and composition were examined using picrosirius red staining, and mast cell infiltration was assessed with toluidine blue staining. Early and late SL stages were compared to identify histomorphological and immunologic correlates of stage progression. We found a predominance of CD4+ T cells and mast cells in SL skin (1.4/mm² versus 1.0/mm², P < 0.01; 1.2/mm² versus 0.2/mm², P < 0.0001) and a higher ratio of collagen III to collagen I fibers (51.6% versus 75.0%, P < 0.001). M2 macrophages were more abundant in late-stage than in early-stage lymphedema (1.7/mm² versus 1.0/mm², P = 0.02). This study demonstrated a shift toward CD4+ T cell and mast cell infiltration in SL skin, correlating with extracellular matrix disorganization and an altered collagen III/I ratio. These findings enhance our understanding of the cellular and morphological changes in SL, potentially guiding future diagnostic and therapeutic strategies.