Amount Of Collagen Research Articles

Self-gripping versus polypropylene mesh for incisional hernia repair in a rat model.

Self-gripping mesh, made of monofilament polypropylene and covered by a layer of polylactic acid micro-hooks, is applied in ventral hernia repair, whereas cytological change and collagen expression around the mesh are rarely reported. The objective of this research was to compare inflammatory response and collagen proliferation between self-gripping and polypropylene mesh in rat model of incisional hernia. Forty-five rats were randomly divided into unrepaired (UR) group, polypropylene (PP) mesh group, and self-gripping (SG) mesh group and euthanized at 1, 2 and 4weeks postoperatively. The levels of inflammation, neovascularization, and collagen expression were measured by immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blot. One rat died and others developed typical incisional hernia in UR group, and hematoma, seroma, or wound infection were not observed in PP and SG groups. There was no significant difference in mesh shrinkage and inflammatory infiltration between PP and SG groups. With regard to neovascularization, 2 groups were comparable at 1 and 2weeks, while the neovascularization score of PP group was statistically higher than that of SG group at 4weeks. One week after surgery, the amounts of Collagen I (Col I) mRNA in PP group were significantly higher than SG group, while the amounts of Collagen III (Col III) mRNA were comparable between 2 groups. Two weeks following operation, the expressions of Col I mRNA and Col III mRNA in PP group were statistically lower than those in SG group. Four weeks postoperatively, the levels of Col I mRNA and Col III mRNA in PP group were significantly higher than those in SG group. Self-gripping mesh induced comparable inflammatory response and collagen proliferation compared with polypropylene mesh in a rat model. ZZU-LAC2023080121.

Structural Adaptations of the Anterolateral Complex of the Knee and Associated Tissues: A Comparative Anatomical and Histological Analysis of Knees With and Without an Anterolateral Ligament.

The anterolateral ligament (ALL) is considered a secondary stabilizer of internal rotation and, due to proximity to the lateral collateral ligament (LCL), it may contribute to anterolateral rotatory stability. This study characterized the anatomy of the ALL and associated tissues of the anterolateral complex (ALC) to determine if structural and histological compensatory adaptations exist in patients without an ALL. Forty-nine cadaveric knees were dissected from distal-to-proximal using established landmarks with the aid of internal rotation stress to localize the ALL (if present), LCL, iliotibial band (ITB), and anterolateral capsule. The width and thickness of ALL and LCL were measured with digital calipers at the origin, middle, and insertion, and cross-sectional areas were calculated. ALL and LCL length and ITB thickness were also obtained. Samples of each tissue were stained with hematoxylin and eosin and picrosirius red, and histological images were evaluated with ImageJ to quantify collagen density (mean gray value [mgv]) and quantity (percent coverage). Size measurements and collagen characteristics were compared between ALL-present and ALL-deficient knees. The ALL was identified in 63% of knees with mean cross-sectional areas of 8.9, 5.8, and 9.7 mm2 at the origin, middle, and insertion, respectively. Mean collagen density of the ALL was 106.9 mgv on a scale of 0 (black) to 255 (white), and overall collagen quantity was 40.3%. Proximal LCL width (p = 0.04), distal LCL thickness (p = 0.03), and cross-sectional area (p = 0.01), and ITB thickness (p = 0.02) were significantly greater in ALL-deficient knees. A significantly higher collagen density was found within the LCL (p = 0.04), and higher overall quantity of collagen within the LCL (p < 0.01) and ITB (p < 0.01), of ALL-deficient knees. Gross anatomical and histological alterations exist in knees without an ALL compared with those with an ALL. These may reflect adaptations in the ALC and LCL that are present to compensate for the absence of the anterolateral rotatory stability afforded by the ALL.

THE PPARG RECEPTOR AGONIST PIOGLITAZONE REDUCES PULMONARY FIBROSIS INDUCED BY BLEOMYCIN ADMINISTRATION IN MICE

The aim of the study was to investigate the possibility of preventing the development of pulmonary fibrosis by activating the PPARG pathway of peroxisome proliferator-activated receptors, in particular, by administering pioglitazone. Materials and methods. The experiment was performed on 60 male BALB/c mice, which were divided into: 1 group of animals received bleomycin (BLM) oropharyngeally (n=35), 2 group of animals received saline (n=25) oropharyngeally. Pulmonary fibrosis was modeled in group 1: bleomycin at a concentration of 1 mg/kg pre-dissolved in 40 μL of saline for 6 days, group 2 was administered saline in a volume of 40 μL for the same period of time. 3 21 days later, the mice were separated: Group 3 OF aspiration with bleomycin combined with oral administration of pioglitazone (BLM+PGL) (n=15), Group 4 received oropharyngeal bleomycin combined with oral administration of saline (BLM+Saline) (n=15), group 5 - oral saline in combination with oral administration of pioglitazone (OP+PGL) (n=10), group 6 – oral saline in combination with oral saline (OP+SGL) (n=10). Animals of groups 3 and 4 received 40 μL of pioglitazone (20 mg/kg) orally for 14 days. Animals of groups 5 and 6 received 40 μL of saline orally for 14 days, respectively. On day 35, animals of all groups were euthanized by intraperitoneal injection of sodium thiopental at a dose of 250 mg/kg, and lung tissue was sampled from each animal for further determination of hydroxyproline levels and histopathological examination. Results. The obtained results demonstrate a significant decrease in the level of lung moisture, the mass ratio of the right lung. The histopathological examination significantly reduced the amount of collagen when comparing the treated group with the control group. Conclusions. Activation of PPARG receptors has a positive effect on the structure of the lungs in mice in the bleomycin model of pulmonary fibrosis in mice. Pioglitazone reduces inflammation in the lungs of mice and decreases collagen content in the lung tissue.

Enhancing Instant Fortified Rice Congee (IFRC) for Elderly Nutrition: Collagen and Curcumin Optimisation Using Response Surface Methodology (RSM)

Instant rice congee (IRC) fortified with functional ingredients has been specifically formulated to provide enhanced nutrition for the elderly. The optimisation of collagen and curcumin amounts in instant fortified rice congee (IFRC) was determined using Response Surface Methodology (RSM). The study revealed that the optimal conditions for IFRC formulation involved incorporating 7.96 g of collagen and 361 mg of curcumin, resulting in the highest observed values for protein content (32.41%), Total Phenolic Content (TPC) at 24.75 mg GAE/g sample, Ferric Reducing Antioxidant Power (FRAP) at 6.03 mg TE/g sample, adhesiveness at -329.23 g/s and cohesiveness at 0.60. In contrast, the formulation exhibited the lowest values for hardness (581.70 g). These findings, derived from the application of RSM, provide valuable insights into the optimal combination of collagen and curcumin in IFRC, showcasing its potential to enhance key nutritional and textural attributes. The outcomes from this study offer practical guidance for utilising collagen and curcumin as functional ingredients in fortified foods, particularly in the context of creating nutritionally enriched and palatable options for the elderly.

Dextromethorphan inhibits collagen and collagen-like cargo secretion to ameliorate lung fibrosis.

Excessive deposition of fibrillar collagen in the interstitial extracellular matrix (ECM) of human lung tissue causes fibrosis, which can ultimately lead to organ failure. Despite our understanding of the molecular mechanisms underlying the disease, no cure for pulmonary fibrosis has yet been found. We screened a drug library and found that dextromethorphan (DXM), a cough expectorant, reduced the amount of excess fibrillar collagen deposited in the ECM in cultured primary human lung fibroblasts, a bleomycin mouse model, and a cultured human precision-cut lung slice model of lung fibrosis. The reduced extracellular fibrillar collagen upon DXM treatment was due to reversible trafficking inhibition of collagen type I (COL1) in the endoplasmic reticulum (ER) in TANGO1- and HSP47-positive structures. Mass spectrometric analysis showed that DXM promoted hyperhydroxylation of proline and lysine residues on various collagens (COL1, COL3, COL4, COL5, COL7, and COL12) and latent transforming growth factor-β-binding protein (LTBP1 and LTBP2) peptides, coinciding with their secretion block. Additionally, proteome profiling of DXM-treated cells showed increased thermal stability of prolyl-hydroxylases P3H2, P3H3, P3H4, P4HA1, and P4HA2, suggesting a change in their activity. Transcriptome analysis of profibrotic stimulated primary human lung fibroblasts and human ex vivo lung slices after DXM treatment showed activation of an antifibrotic program through regulation of multiple pathways, including the MMP-ADAMTS axis, WNT signaling, and fibroblast-to-myofibroblast differentiation. Together, these data obtained from in vitro, in vivo, and ex vivo models of lung fibrogenesis show that DXM has the potential to limit fibrosis through inhibition of COL1 membrane trafficking in the ER.

THE MOLECULAR MECHANISM, TYPES AND TREATMENT OF SCAR FORMATION

Wound healing and scar formation is a complex biological process that occurs as a response to injury, characterized by the deposition of extracellular matrix components and the proliferation of fibroblasts. The mechanisms underlying wound healing and following scar formation can vary significantly depending on the type of scar, such as hypertrophic scars and keloids, and are influenced by various cellular and molecular factors. Myofibroblasts, a differentiated form of fibroblasts, play a pivotal role in wound healing and scar formation due to their contractile properties and ability to produce large amounts of collagen and other extracellular matrix components. Scar formation process involves complex interactions among various cell types, including fibroblasts, macrophages, and endothelial cells, as well as the extracellular matrix components. Understanding these mechanisms is crucial for developing therapeutic strategies to minimize pathological scarring, such as hypertrophic scars and keloids. The initial phase of scar formation is dominated by inflammation, which is essential for initiating the healing process. Inflammatory cells, particularly macrophages, play a pivotal role in orchestrating the wound healing response. Fibroblasts are the primary effector cells in scar formation, responsible for synthesizing extracellular matrix components, including collagen. Scars can be classified into several types based on their characteristics, underlying mechanisms, and clinical presentations. The two most commonly discussed types of scars are hypertrophic scars and keloids, but there are also atrophic scars, contracture scars, and acne scars, each with distinct features and implications for treatment. The aim of this study is to explain the molecular mechanism, types and treatment of scar formation.

Designing lysyl hydroxylase inhibitors for oral submucous fibrosis - Insights from molecular dynamics.

Alpha-ketoglutarate (αKG) dependent Lysyl hydroxylase (LH) is a critical enzyme in the post-translational conversion of lysine into hydroxylysine in collagen triple helix and telopeptide regions. Overexpression of LH increases collagen hydroxylation and covalent cross-linkage, causing fibrosis. Currently, no drugs are available to inhibit LH potentially. Virtual screening of the Zinc database was employed to identify new leads. They were docked using Glide. Lead1 complex exhibits a notably superior docking score compared to other leads. This complex hinders iron stabilization by engaging with the HXD..Xn..H motif and competitively inhibiting 2OG binding at the catalytic site via interactions with Cys691 and Arg729 by forming a salt bridge. Molecular dynamics simulations over a 500 ns time scale and molecular mechanics Poisson-Boltzmann surface area calculations illustrate the stable binding of Leads. DCCA analysis finds the coordinated residue motions and the influence of the second coordinating sphere in long-range interactions. In-silico results were validated by quantifying the amount of collagen in zebrafish through histology and hydroxyproline assay. These findings demonstrated a reduction in collagen deposition in the treated samples compared to the positive control. This computational study unveiled insights into how leads may impede collagen lysine hydroxylation and potentially impact collagen-related processes.

Biomechanical modelling infers that collagen content within peripheral nerves is a greater indicator of axial Young's modulus than structure.

The mechanical behaviour of peripheral nerves is known to vary between different nerves and nerve regions. As the field of nerve tissue engineering advances, it is vital that we understand the range of mechanical regimes future nerve implants must match to prevent failure. Data on the mechanical behaviour of human peripheral nerves are difficult to obtain due to the need to conduct mechanical testing shortly after removal from the body. In this work, we adapt a 3D multiscale biomechanical model, developed using asymptotic homogenisation, to mimic the micro- and macroscale structure of a peripheral nerve. This model is then parameterised using experimental data from rat peripheral nerves and used to investigate the effect of varying the collagen content, the fibril radius and number density, and the macroscale cross-sectional geometry of the peripheral nerve on the effective axial Young's moduli of the whole nerve. Our results indicate that the total amount of collagen within a cross section has a greater effect on the axial Young's moduli compared to other measures of structure. This suggests that the amount of collagen in a cross section of a peripheral nerve, which can be measured through histological and imaging techniques, is one of the key metrics that should be recorded in the future experimental studies on the biomechanical properties of peripheral nerves.

Intradermal delivery of a liposomal formulation encapsulating amphiphilic ascorbic acid by iontophoresis for promotion of collagen synthesis

Collagen is a structural protein in skin that is an important component for maintaining skin functions, such as elasticity. As the amount and functional capacity of collagen in the skin decreases with age, wrinkles and skin sagging are induced. Treatment of the skin with vitamin C (ascorbic acid, AsA) is attracting attention as a means of inducing collagen production. However, penetration of AsA into the skin is difficult due to its hydrophilicity. To overcome this limitation, we focused on a combination of iontophoresis (ItP), which is a non-invasive intradermal drug delivery technology, and use of a liposome formulation, to improve skin penetration of AsA. In this study, palmitoylated AsA was used to increase the encapsulation efficiency into liposomes. We prepared liposomes encapsulating palmitoylated AsA (AsA-lipo) and performed ItP of fluorescently-labeled AsA-lipo on the shaved dorsal skin of rats. Fluorescence of the liposomes was observed in skin sections following ItP, indicating that AsA-lipo was delivered into the skin. The amount of collagen in the skin after ItP of AsA-lipo increased with the number of doses, and the amount of collagen mRNA also showed an increasing trend. Furthermore, the amount of hydroxyproline, which is a major component of collagen, was significantly increased in skin treated with AsA-lipo via ItP. In conclusion, results of this study demonstrate the successful promotion of skin collagen synthesis by non-invasive iontophoretic intradermal delivery of AsA-lipo.

The Potential Applications of Natural Colostrum in Skin Health

Skin is a crucial organ for preserving the body’s equilibrium. Like other parts of the body, skin also ages due to extrinsic and intrinsic factors, leading to several signs such as wrinkles, spots, and a decline in elasticity, causing a range of issues similar to those seen elsewhere in the body. Some of these factors include ultraviolet (UV) radiation, hormonal disorders, genetic factors, loss of moisture, metabolic disorders, exposure to chemicals, and smoking. Colostrum, which is the initial foremilk, has shown positive effects on the consequences of these factors. Its content is richer than mature milk and contains several beneficial components. For instance, it includes hyaluronic acid, a molecule that binds water and keeps the skin hydrated; lactoferrin, with high antimicrobial properties; immunoglobulins, which are responsible for immunity; growth factors, which increase the amount of collagen, the main protein type of the skin; and, finally, the telomerase enzyme, which maintains the telomere’s length and, thus, decelerates the aging process. It has recently become apparent that using skin products with natural ingredients is essential. Considering its nature, contents, and effects, colostrum stands out as an excellent material for the cosmetic industry, especially for the aging sector. Therefore, the aim of this review article is to demonstrate the potential application of natural colostrum in skin health and its usage in natural cosmetic products in the cosmetic sector.

Allium sativum nanovesicles exhibit anti-inflammatory and antifibrotic activity in a bleomycin-induced lung fibrosis model.

Idiopathic pulmonary fibrosis (IPF) is a chronic and highly fatal disease characterized by excessive accumulation of extracellular matrix (ECM), foci of myofibroblasts, and a usual pattern of interstitial pneumonia. As suggested by international guidelines, the treatment for this disease involves supportive therapies, as there is currently no effective treatment. Plant-derived nanovesicles have emerged as a new treatment for various diseases and have been tested in cellular and murine models. This research aimed to test the use of Allium sativum nanovesicles (AS-NV) in a murine model of IPF induced by bleomycin. AS-NV reduced the amount of collagen and restored lung architecture in the mouse model. AS-NV was tested on human lung fibroblasts, which do not affect the viability of healthy cells. AS-NV treatment decreases the mRNA levels of genes related to fibrosis, inflammation, and ECM deposition (Mmp2,Timp-2,Vegf,Pcna,Col1a1,Tgf-β,α-Sma,IL-1β,and Hif1a) in bleomycin-induced idiopathic pulmonary fibrosis. This research highlights the anti-inflammatory and antifibrotic activity of AS-NV, which contributes to plant nanovesicle mechanisms in IPF; however, more AS-NV studies are needed to identify alternative treatments for idiopathic pulmonary fibrosis.

The histological growth patterns in liver metastases from colorectal cancer display differences in lymphoid, myeloid, and mesenchymal cells.

Colorectal liver metastases grow following different histologic growth patterns (HGPs), classified as desmoplastic and nondesmoplastic (dHGP, non-dHGP), being the latter associated with worst prognosis. This study aimed to investigate the tumor microenvironment (TME) between HGPs supporting different survival. Multiplexed immunohistochemical staining was performed with the Opal7 system in a 100-patients cohort to evaluate the tumor-liver interface with three different cell panels: lymphoid, myeloid, and carcinoma-associated fibroblasts. Differences between HGPs were assessed by Mann-Whitney U test with Pratt correction and Holm-Bonferroni multitest adjustment. Cytotoxic T-cells were more abundant in tumoral areas of dHGP, while non-dHGP had higher macrophages infiltration, Th2, CD163+, and Calprotectin+ cells as well as higher pSMAD2 expression. Regarding carcinoma-associated fibroblasts, several subsets expressing COL1A1 were enriched in dHGP, while αSMAlow_single cells were present at higher densities in non-dHGP. Interestingly, Calprotectin+ cells confer better prognoses in non-dHGP, identifying a subgroup of good outcome patients that unexpectedly also show an enrichment in other myeloid cells. In summary, our results illustrate different TME landscapes with respect to HGPs. dHGP presents a higher degree of immunocompetence, higher amounts of Collagen 1 as well as lesser presence of myeloid cell populations, features that might be influencing on the better prognosis of encapsulated metastases.

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.

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.

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.

IL-11 Expression in Systemic Sclerosis Is Dependent on Caspase-1 Activity but Does Not Increase Collagen Deposition

Background: Interleukin-11 (IL-11) is increased in patients with systemic sclerosis (SSc) and is thought to play a role in fibrosis. Many studies have reported decreased fibrosis when IL-11 is blocked, but few have examined factors that induce IL-11 expression. Because fibrosis has been linked to activated inflammasomes driving caspase-1 maturation and the secretion of IL-1β, we set out to determine if IL-11 expression was dependent on caspase-1 activity. Methods: Primary lung fibroblast cell lines derived from patients with SSc, IPF (fibrotic control), and healthy individuals were cultured at low passage. Gene expression for IL-11 and the IL-11 receptor (IL-11Rα1) was analyzed using qPCR and normalized to the control, and collagen production was measured using Sirius Red. Results: SSc and IPF fibroblasts expressed significantly more IL-11 transcripts than normal cells (3.35-fold and 9.97-fold more, p = 0.0396 and p = 0.0023, respectively). IL-11Rα1 was expressed 2.32-fold and 2.27-fold more in SSc and IPF (p = 0.0004 and p = 0.0032, respectively) than in normal cells. In SSc fibroblasts, inhibition of caspase-1 with YVAD decreased IL-11 expression by 49.59% (p = 0.0016) but did not affect IL-11Rα1 expression (p &gt; 0.05). IL-11 expression was increased 2.97-fold with TGF-β1 (p = 0.0030) and 22.24-fold with IL-1β (p &lt; 0.0001), while the expression of IL-11Rα1 was not induced with these two cytokines. LPS increased IL-11 expression in normal fibroblasts 1.52-fold (p = 0.0042), which was abolished with YVAD (p &lt; 0.0001). IL-11Rα1 gene transcripts were also increased with LPS 1.50-fold (p = 0.0132), but YVAD did not inhibit this expression. In these studies, we were unable to detect IL-11 protein nor were we able to induce COL1A1 expression or increase the total amount of collagen secreted by fibroblasts with human recombinant IL-11. Conclusions: IL-11 and its receptor, IL-11Rα1, are both elevated in fibrosis. IL-11 expression is dependent on inflammasome activation of caspase-1 and the downstream cytokines TGF-β1 and IL-1β, while IL-11Rα1 was only dependent on NF-kB.

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.