Elevated serum levels of anti-collagen type I antibodies in patients with spontaneous cervical artery dissection and ischemic stroke: a prospective multicenter study.

Introduction: Spontaneous cervical artery dissection (sCAD) is a rare vasculopathy whose trigger is still unknown. We hypothesized that autoimmunity against components of the vascular wall might play a critical role in sCAD and examined anti-collagen type I antibodies in patients with sCAD, acute ischemic stroke, patients with thromboendarterectomy, and controls. Methods: Fifty-seven patients with sCAD (age 45.7 ± 10.2 years, female 18 (31.6%)) were prospectively enrolled in four German stroke centers. Blood samples were collected at baseline, at day 10 ± 3, and after 6 ± 1 months. Patients with ischemic stroke not related to CAD (n=54, age 56.7 ± 13.7 years, female 15 (27.8%)), healthy probands (n=80, age 57.4 ± 12.9 years, female 56 (70%)), and patients undergoing thromboendarterectomy of the carotid artery (n=9, age 70.7 ± 9.3 years, female 2 (22.2%)) served as controls. Anti-collagen type I antibodies were determined by enzyme-linked immunosorbent assays (ELISAs). Results: Patients with acute sCAD had higher serum levels of anti-collagen type I antibodies (33.9 ± 24.6 µg/ml) than probands (18.5 ± 11.0 µg/ml; p <0.001) but lower levels than patients with ischemic stroke not related to sCAD (47.8 ± 28.4 µg/ml; p=0.003). In patients with sCAD, serum levels of anti-collagen type I antibodies were similar in the acute, subacute, and chronic phase. Levels of anti-collagen type I antibodies significantly correlated with circulating collagen type I (rho=0.207, p=0.003). Conclusion: Anti-collagen type I antibodies seem not to represent a trigger for acute sCAD or ischemic stroke but may rather be linked to the metabolism and turnover of collagen type I.

Eggshell membrane as promising supplement to maintain bone health: A systematic review.

Bone loss is a well-known phenomenon in the older population leading to increased bone fracture risk, morbidity, and mortality. Supplementation of eggshell membrane (ESM) is evaluated due to its possible application to prevent bone loss and usage in osteoporosis therapy. The similar organic chemical composition of ESM and human bone is described in detail as both mainly consist of collagen type I, chondroitin sulfate, dermatan sulfate, hyaluronic acid and elastan. ESM and its components are reported to improve mineralization in bone tissue. In many studies ESM intake reduced pain in patients with joint disorders and reduced inflammatory processes. Additionally, ESM improved calcium uptake in human cells. These findings in comparison with a clinical pilot study reporting pain reduction in osteoporotic patients and increased osteoblast activity in in vitro assays support ESM to be a beneficial supplement for bone health. In this systematic review we combined chemical structure analysis with clinical studies to give a more comprehensive picture with novel explanations.

Zinc Iodide Dimethyl Sulfoxide Reduces Collagen Deposition by Increased Matrix Metalloproteinase-2 Expression and Activity in Lung Fibroblasts.

Chronic inflammatory lung diseases are characterized by disease-specific extracellular matrix accumulation resulting from an imbalance of matrix metalloproteinases (MMPs) and their inhibitors. Zinc is essential for the function of MMPs, and zinc deficiency has been associated with enhanced tissue remodeling. This study assessed if zinc iodide (ZnI) supplementation through dimethyl sulfoxide (DMSO) modifies the action of MMPs in isolated human lung fibroblasts. The expression and activity of two gelatinases, MMP-2 and MMP-9, were determined by gelatin zymography and enzyme-linked immuno-sorbent assay (ELISA). Collagen degradation was determined by cell-based ELISAs. Collagen type I and fibronectin deposition was stimulated by human recombinant tumor growth factor ß1 (TGF-ß1). Untreated fibroblasts secreted MMP-2 but only minute amounts of MMP-9. TGF-ß1 (5 ng/mL) reduced MMP-2 secretion, but stimulated collagen type I and fibronectin deposition. All the effects of TGF-ß1 were significantly reduced in cells treated with ZnI-DMSO over 24 h, while ZnI and DMSO alone had a lower reducing effect. ZnI-DMSO alone did not increase MMP secretion but enhanced the ratio of active to inactive of MMP-2. ZnI alone had a lower enhancing effect than ZnI-DMSO on MMP activity. Furthermore, MMP-2 activity was increased by ZnI-DMSO and ZnI in the absence of cells. Soluble collagen type I increased in the medium of ZnI-DMSO- and ZnI-treated cells. Blocking MMP activity counteracted all the effects of ZnI-DMSO. Conclusion: The data suggest that the combination of ZnI with DMSO reduces fibrotic processes by increasing the degradation of collagen type I by up-regulating the activity of gelatinases. Thus, the combination of ZnI with DMSO might be considered for treatment of fibrotic disorders of the lung. DMSO supported the beneficial effects of ZnI.

Biomarkers and Biochemical Indicators to Evaluate Bone Metabolism in Preterm Neonates.

The purpose of the present study was to evaluate the concentrations of some bone turnover markers in preterm neonates with uncomplicated clinical course in the first month of life. Samples from 13 preterm neonates were collected at three different times: at birth (T0) from umbilical cord blood (UCB); and at 15 (T1) and 30 (T2) days of life from peripheral blood (PB). The concentrations of calcium (Ca), phosphate (P), total alkaline phosphatase (ALP), Collagen Type 1 Amino-terminal Propeptide (PINP), osteocalcin (OC), Collagen Type 1 Carboxyl-Terminal Telopeptide (CTX) and Leptin were assessed. A statistically significant difference for ALP concentration at birth versus T1 and T2 was found. An evident increase in the median concentrations of CTX, OC and PINP from T0 to T2 were observed. A significant difference was also found for Leptin concentration at T0 compared to T1. In preterm infants, in the absence of acute or chronic medical conditions and without risk factors for metabolic bone disease (MBD) of prematurity, there is a significant increase in bone turnover markers during the first month of life. The knowledge of the variations in these markers in the first weeks of life, integrated by the variations in the biochemical indicators of bone metabolism, could help in recognizing any conditions at risk of developing bone diseases.

Establishment of homotrimer collagen type I signature and its association with clinical manifestation and tertiary lymphoid structures formation in liver cancer.

Background: collagen type I is a fundamental composition of extracellular matrix. Typically it exists in the form of a heterotrimer, consisting of two α1 chains encoded by COL1A1 and one α2 chain encoded by COL1A2. However, in cancer a homotrimeric form of collagen type I comprises three α1 chains encoded by COL1A1 was founded. There is still a lack of transcriptional and histologic methods for detecting homotrimeric collagen type I. Furthermore, a comprehensive analysis of the pan-cancer distribution pattern and clinical relevance of homotrimeric collagen type I is conspicuously absent. Method: Using transcriptional and immunoflourance method, we established homocol signature, which is able to transcriptionally and histologically detect homotrimeric collagen type I. We investigated the diagnostic and prognostic potential of homocol as a novel cancer biomarker in a pan-cancer cohort. Furthermore, we assessed its association with clinical manifestations in a liver cancer cohort undergoing treatment at our institute. Result: Homotrimer Collagen Type I is predominantly expressed by cancer cells and is linked to several critical cancer hallmarks, particularly inflammatory response and proliferation. Survival analyses have indicated that a high Homocol expression is correlated with poor outcomes in most types of cancer studied. In terms of cancer detection, Homocol demonstrated strong performance in Receiver Operating Characteristic (ROC) analysis, with an Area Under Curve (AUC) of 0.83 for pan-cancer detection and between 0.72 and 0.99 for individual cancers.In cohorts undergoing PD1 treatment, we noted a higher presence of Homocol in the response group. In a Hepatocellular Carcinoma (HCC) clinical set, high Homocol expression was associated with an increased formation of intra-tumor tertiary lymphoid structures (TLS), larger tumor sizes, more advanced Barcelona Clinic Liver Cancer (BCLC) stages, higher microvascular invasion (MVI) grades, absence of a capsule, and an enriched para-tumor collagen presence. Conclusion: our research has led to the development of a novel gene signature that facilitates the detection of Homotrimer Collagen Type I. This may greatly assist efforts in cancer detection, prognosis, treatment response prediction, and further research into Homotrimer Collagen Type I.

Bone collagen tensile properties of the aging human proximal femur.

Despite the dominant role of bone mass in osteoporotic fractures, aging bone tissue properties must be thoroughly understood to improve osteoporosis management. In this context, collagen content and integrity are considered important factors, although limited research has been conducted on the tensile behavior of demineralized compact bone in relation to its porosity and elastic properties in the native mineralized state. Therefore, this study aims (i) at examining the age-dependency of mineralized bone and collagen micromechanical properties; (ii) to test whether, and if so to which extent, collagen properties contribute to mineralized bone mechanical properties. Two cylindrical cortical bone samples from fresh frozen human anatomic donor material were extracted from 80 proximal diaphyseal sections from a cohort of 24 female and 19 male donors (57 to 96 years at death). One sample per section was tested in uniaxial tension under hydrated conditions. First, the native sample was tested elastically (0.25 % strain), and after demineralization, up to failure. Morphology and composition of the second specimen was assessed using micro-computed tomography, Raman spectroscopy, and gravimetric methods. Simple and multiple linear regression were employed to relate morphological, compositional, and mechanical variables with age and sex. Macro-tensile properties revealed that only elastic modulus of native samples was age dependent whereas apparent elastic modulus was sex dependent (p < 0.01). Compositional and morphological analysis detected a weak but significant age and sex dependency of relative mineral weight (r = -0.24, p < 0.05) and collagen disorder ratio (I∼1670/I∼1640, r = 0.25, p < 0.05) and a strong sex dependency of bone volume fraction while generally showing consistent results in mineral content assessment. Young's modulus of demineralized bone was significantly related to tissue mineral density and Young's modulus of native bone. The results indicate that mechanical properties of the organic phase, that include collagen and non-collagenous proteins, are independent of donor age. The observed reduction in relative mineral weight and corresponding overall stiffer response of the collagen network may be caused by a reduced number of mineral-collagen connections and a lack of extrafibrillar and intrafibrillar mineralization that induces a loss of waviness and a collagen fiber pre-stretch.

Content and tissue expression of Collagen I, Collagen IV, and Laminin in the Extracellular Matrix in Prostate Adenocarcinoma.

Prostate cancer is one of the most common neoplasm in the male population. It is not known why some tumors become more aggressive than others. Although most studies show changes in the expression of cell adhesion molecules and the extracellular matrix correlated with the Gleason score, no study has objectively measured the tissue content of these molecules. This study aims to measure the content and tissue expression of collagen type I and IV and laminin in the extracellular matrix of patients with prostate adenocarcinoma and correlate these findings with the Gleason score and clinical characteristics. Forty-one patients who underwent radical prostate surgery at the Urology Department of a reference Hospital in Brazil between January 2015 and December 2020 were studied. The tissue protein content was estimated under light microscopy at a final magnification of 200 × . The mean collagen I score in prostate adenocarcinoma tissue samples was 7.16 ± 1.03 pixels/field. The mean type IV collagen score was 3.44 ± 0.61 pixels/field. The mean laminin score was 5.19 ± 0.79 pixels/field. The total Gleason score was correlated with both collagen and laminin. All the correlations were negative, which shows that the higher the collagen/laminin expression was, the lower the total Gleason score (p-value < 0,05). According to the Pearson correlation analysis, age has no statistical relationship with collagen and laminin content. PSA, in turn, showed a correlation only with laminin, but r = -0.378 (p = 0.015). Among the associated diseases and lifestyle habits, there is only statistical significance in the comparison of alcoholism for collagen I. For collagen IV and laminin, no statistical significance was obtained with the clinical variables analyzed.

Fibrillar extracellular matrix produced by pericyte-like cells facilitates glioma cell dissemination.

Gliomagenesis induces profound changes in the composition of the extracellular matrix (ECM) of the brain. In this study, we identified a cellular population responsible for the increased deposition of collagen I and fibronectin in glioblastoma. Elevated levels of the fibrillar proteins collagen I and fibronectin were associated with the expression of fibroblast activation protein (FAP), which is predominantly found in pericyte-like cells in glioblastoma. FAP+ pericyte-like cells were present in regions rich in collagen I and fibronectin in biopsy material and produced substantially more collagen I and fibronectin in vitro compared to other cell types found in the GBM microenvironment. Using mass spectrometry, we demonstrated that 3D matrices produced by FAP+ pericyte-like cells are rich in collagen I and fibronectin and contain several basement membrane proteins. This expression pattern differed markedly from glioma cells. Finally, we have shown that ECM produced by FAP+ pericyte-like cells enhances the migration of glioma cells including glioma stem-like cells, promotes their adhesion, and activates focal adhesion kinase (FAK) signaling. Taken together, our findings establish FAP+ pericyte-like cells as crucial producers of a complex ECM rich in collagen I and fibronectin, facilitating the dissemination of glioma cells through FAK activation.

Plasma-Activated Polydimethylsiloxane Microstructured Pattern with Collagen for Improved Myoblast Cell Guidance.

We focused on polydimethylsiloxane (PDMS) as a substrate for replication, micropatterning, and construction of biologically active surfaces. The novelty of this study is based on the combination of the argon plasma exposure of a micropatterned PDMS scaffold, where the plasma served as a strong tool for subsequent grafting of collagen coatings and their application as cell growth scaffolds, where the standard was significantly exceeded. As part of the scaffold design, templates with a patterned microstructure of different dimensions (50 × 50, 50 × 20, and 30 × 30 µm2) were created by photolithography followed by pattern replication on a PDMS polymer substrate. Subsequently, the prepared microstructured PDMS replicas were coated with a type I collagen layer. The sample preparation was followed by the characterization of material surface properties using various analytical techniques, including scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS). To evaluate the biocompatibility of the produced samples, we conducted studies on the interactions between selected polymer replicas and micro- and nanostructures and mammalian cells. Specifically, we utilized mouse myoblasts (C2C12), and our results demonstrate that we achieved excellent cell alignment in conjunction with the development of a cytocompatible surface. Consequently, the outcomes of this research contribute to an enhanced comprehension of surface properties and interactions between structured polymers and mammalian cells. The use of periodic microstructures has the potential to advance the creation of novel materials and scaffolds in tissue engineering. These materials exhibit exceptional biocompatibility and possess the capacity to promote cell adhesion and growth.

Efficacy and Safety of Spinal Collagen Mesotherapy in Patients with Chronic Low Back Pain in a Three-Month Follow-Up-Retrospective Study.

Background: Low back pain syndrome is associated with muscular and myofascial pain and is linked with muscle overstrain or a lack of regular physical activity as well as a habitual bad posture, which cause the overload of perispinal soft tissues. One of the forms of therapy of LBP is the mesotherapy of the spine, which consists of multi-point micro-injections of drugs or medicine mixtures, which include preparations of collagen type I. The aim of the study was to assess the efficacy and safety of mesotherapy with collagen type I. Methods: A retrospective analysis of the results of the treatment of patients with chronic low back pain syndrome using mesotherapy was performed. A total of 130 patients (83 women and 47 men; mean age: 51 ± 14 years) were divided into two groups: group I (n = 65), treated with collagen type I, and group II (n = 65), treated with lignocaine 1%. Mesotherapy was performed weekly over five weeks. Patients were assessed using the following scales: the VAS, Laitinen Scale, and Revised Oswestry Low Back Pain Disability Scale before the start of the treatment, after five treatments, and at the three-month follow-up visit. Results: A statistically significant improvement was observed after the use of spinal mesotherapy both with collagen type I and lignocaine, with the collagen treatment having better results at the three-month follow-up visit. No adverse effects were observed after the procedures. Conclusions: Spinal mesotherapy using collagen type I and lignocaine seems to be an effective method in the treatment of chronic LBP. Collagen mesotherapy gives better results in the long term. Mesotherapy is a safe form of therapy.

Cirrhotic-extracellular matrix attenuates aPD-1 treatment response by initiating immunosuppressive neutrophil extracellular traps formation in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is closely associatedwith chronic liver diseases, particularly liver cirrhosis, which has an altered extracellular matrix (ECM) composition. The influence and its mechanism of the cirrhotic-ECM on the response of HCC to immune checkpoint inhibitor (ICI) remains less clarified. METHODS: In silico, proteomic and pathological assessment of alteration of cirrhotic-ECM were applied in clinical cohort. Multiple pre-clinical models with ECM manipulation were used to evaluate cirrhotic-ECM's effect on ICI treatment. In silico, flow cytometry and IHC were applied to explore how cirrhotic-ECM affect HCC microenvironment. In vitro and in vivo experiments were carried out to identify the mechanism of how cirrhotic-ECM undermined ICI treatment. RESULTS: We defined "a pro-tumor cirrhotic-ECM" which was featured as the up-regulation of collagen type 1 (Col1). Cirrhotic-ECM/Col1 was closely related to impaired T cell function and limited anti PD-1 (aPD-1) response of HCC patients from the TCGA pan cancer cohort and the authors' institution, as well as in multiple pre-clinical models. Mechanically, cirrhotic-ECM/Col1 orchestrated an immunosuppressive microenvironment (TME) by triggering Col1-DDR1-NFκB-CXCL8 axis, which initiated neutrophil extracellular traps (NETs) formation to shield HCC cells from attacking T cells and impede approaching T cells. Nilotinib, an inhibitor of DDR1, reversed the neutrophils/NETs dominant TME and efficiently enhanced the response of HCC to aPD-1. CONCLUSIONS: Cirrhotic-ECM modulated a NETs enriched TME in HCC, produced an immune suppressive TME and weakened ICI efficiency. Col1 receptor DDR1 could be a potential target synergically used with ICI to overcome ECM mediated ICI resistance. These provide a mechanical insight and novel strategy to overcome the ICI resistance of HCC.

Evaluation of t-DARPP Expression Alteration in Association with DDR1 Expression in Non-Small Cell Lung Cancer.

Background: Discoidin domain receptor 1 (DDR1) signaling plays a critical role in various cellular functions. Increased DDR1 expression has been shown in different human cancers. t-DARPP is a truncated isoform of DARPP-32, and its upregulation promotes cell survival and migration. Most lung cancer patients have non-small cell lung cancer (NSCLC), and their survival rate is low. Therefore, it is necessary to study new and effective targeted therapies. Increased t-DARPP expression in NSCLC patients is associated with patient survival and can act as a prognostic marker correlated with increasing stages of NSCLC. The current study aimed to evaluate alteration in DDR1 expression and its effects on t-DARPP expression in NSCLC. Methods: Two human lung adenocarcinoma cell lines, A549 and Calu-3, were treated with collagen type I and transfected with DDR1 siRNA. The relative expression of DDR1 and t-DARPP was evaluated using qRT-PCR. Results: The results indicated that collagen type I could stimulate DDR1 expression in NSCLC cells. Also, DDR1 upregulation resulted in a significant increase in t-DARPP expression. In contrast, suppression of DDR1 expression significantly decreased t-DARPP expression. Conclusion: Our findings propose that modification in the expression of DDR1, caused by collagen type I and siRNA, might influence the expression of t-DARPP in NSCLC that is linked to NSCLC progression. Moreover, this alteration could potentially serve as an innovative target for therapeutic intervention.

Is Osteogenesis Imperfecta Associated with Cardiovascular Abnormalities? A Systematic Review of the Literature.

Osteogenesis imperfecta (OI) is a rare genetic disorder caused by abnormal collagen type I production. While OI is primarily characterized by bone fragility and deformities, patients also have extraskeletal manifestations, including an increased risk of cardiovascular disease. This review provides a comprehensive overview of the literature on cardiovascular diseases in OI patients in order to raise awareness of this understudied clinical aspect of OI and support clinical guidelines. In accordance with the PRISMA guidelines, a systematic literature search in PubMed, Embase, Web of Science and Scopus was conducted that included articles from the inception of these databases to April 2023. Valvular disease, heart failure, atrial fibrillation, and hypertension appear to be more prevalent in OI than in control individuals. Moreover, a larger aortic root was observed in OI compared to controls. Various cardiovascular diseases appear to be more prevalent in OI than in controls. These cardiovascular abnormalities are observed in all types of OI and at all ages, including young children. As there are insufficient longitudinal studies, it is unknown whether these abnormalities are progressive in nature in OI patients. Based on these findings, we would recommend referring individuals with OI to a cardiologist with a low-threshold.

Down-regulation of COL1A1 inhibits tumor-associated fibroblast activation and mediates matrix remodeling in the tumor microenvironment of breast cancer.

We investigated the effects of collagen type I alpha 1 (COL1A1) on tumor-associated fibroblast activation and matrix remodeling in the tumor microenvironment of breast cancer. Cells were divided into the blank control, negative control, and siRNA-COL1A1 groups, or HKF control, HKF + exosomes (EXO), HKF + siRNA negative control-EXO, and HKF + siRNA-COL1A1-EXO co-culture groups. Western blot and quantitative real-time PCR detected gene expressions. COL Ⅰ, COL Ⅲ, and TGF-ß1 were detected by enzyme-linked immunosorbent assay. We found that compared with blank and negative control groups, COL1A1 expression and the secretion of exosomes by breast cancer cells were inhibited in the siRNA-COL1A1 group. Compared with the HKF control group, the COL Ⅰ, COL Ⅲ, TGF-ß1, α-SMA, and fibroblast activation protein (FAP) were increased, while the E-cadherin and CAV-1 were decreased in the HKF + EXO, HKF + siRNA negative control-EXO, and HKF + siRNA-COL1A1-EXO co-culture groups. Compared with HKF + EXO and HKF + siRNA negative control-EXO co-culture groups, the COL Ⅰ, COL Ⅲ, TGF-ß1, α-SMA, and FAP were decreased, and the E-cadherin and CAV-1 were increased in the HKF + siRNA-COL1A1-EXO co-culture group. Collectively, COL1A1 down-regulation may inhibit exosome secretion possibly via inhibiting COL Ⅰ and upregulating CAV-1, thereby inhibiting tumor-associated fibroblast activation and matrix remodeling in the tumor microenvironment.

Periplaneta americana extract attenuates hepatic fibrosis progression by inhibiting collagen synthesis and regulating the TGF-ß1/Smad signaling pathway.

INTRODUCTION: Liver fibrosis is the damage repair response following chronic liver diseases. Activated hepatic stellate cells (HSCs) are the main extracellular matrix (ECM)-producing cells and key regulators in liver fibrosis. Periplaneta americana shows prominent antifibrotic effects in liver fibrosis; however, the underlying mechanisms remain undetermined. This study aimed to elucidate the therapeutic effects of P. americana extract (PA-B) on liver fibrosis based on the regulation of the TGF-ß1/Smad signal pathway. MATERIAL AND METHODS: HSCs and Sprague Dawley rats were treated with TGF-ß1 and CCl4, respectively, to establish the hepatic fibrosis model in vitro and in vivo. The effect of PA-B on liver rat fibrosis was evaluated by biochemical (serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), hyaluronic acid (HA), laminin (LN), collagen type IV (Col-IV), pro-collagen type III (PC-III)) and histological examinations. Further, fibrogenic markers expression of alpha smooth muscle actin (α-SMA), collagen type I (Col-I), and collagen type III (Col-III), and the TGF-ß1/Smad pathway-related factors were assessed by immunofluorescence (IF), real time quantitative polymerase chain reaction (RT-qPCR), and western blotting (WB). RESULTS: Treatment of HSC-T6 cells with PA-B suppressed the expression of α-SMA, Col-I, and Col-III, downregulated the expression of TGF-ß1 receptors I and II (TßR I and TßR II, respectively), Smad2, and Smad3, and upregulated Smad7 expression. PA-B mitigates pathologic changes in the rat model of liver fibrosis, thus alleviating liver index, and improving liver function and fibrosis indices. The effects of PA-B on the expression of α-SMA, Col-I, Col-III, TßR I, TßR II, Smad2, Smad3, and Smad7 were consistent with the in vitro results, including reduced TGF-ß1 expression. CONCLUSIONS: The therapeutic effect of PA-B on liver fibrosis might involve suppression of the secretion and expression of TGF-ß1, regulation of the TGF-ß1/Smad signaling pathway, and inhibition of collagen production and secretion.

An Atelocollagen Injection Enhances the Healing of Nonoperatively Treated Achilles Tendon Tears: An Experimental Study in Rats.

Background: There is growing interest in nonoperative treatment for the management of Achilles tendon ruptures (ATRs). However, nonoperative treatment is limited by the risk of tendon reruptures and low satisfaction rates. Recently, atelocollagen injections have been reported to have beneficial effects on tendon healing. Purpose: To evaluate the beneficial effects of injected atelocollagen on Achilles tendon healing and investigate the mechanism of atelocollagen on tendon healing. Study Design: Controlled laboratory study. Methods: Percutaneous tenotomy of the right Achilles tendon in 66 rats was performed. The animals were equally divided into the noninjection group (NG) and the collagen injection group (CG). At 1, 3, and 6 weeks, the Achilles functional index, cross-sectional area, load to failure, stiffness, stress, and the modified Bonar score were assessed. Transmission electron microscopy, western blotting, and immunohistochemistry were also performed. Results: The Achilles functional index (-6.8 vs -43.0, respectively; P = .040), load to failure (42.1 vs 27.0 N, respectively; P = .049), and stiffness (18.8 vs 10.3 N/mm, respectively; P = .049) were higher in the CG than those in the NG at 3 weeks. There were no significant differences in histological scores between the 2 groups. Transmission electron microscopy analysis showed that the mean diameter of collagen fibrils in the CG was greater than that in the NG at 3 weeks (117.2 vs 72.6 nm, respectively; P < .001) and 6 weeks (202.1 vs 144.0 nm, respectively; P < .001). Western blot analysis showed that the expression of collagen type I in the CG was higher than that in the NG at 1 week (P = .005) and 6 weeks (P = .001). Conclusion: An atelocollagen injection had beneficial effects on the healing of nonoperatively treated Achilles tendon injuries. The Achilles tendon of CG rats exhibited better functional, biomechanical, and morphological outcomes compared with NG rats. The molecular data indicated that the mechanism of atelocollagen injections may be associated with an increased amount of collagen type I. Clinical Relevance: An atelocollagen injection might be a good adjuvant option for the nonoperative treatment of ATRs.

NGS analysis of collagen type I genes in Polish patients with Osteogenesis imperfecta: a nationwide multicenter study.

Osteogenesis imperfecta (OI) is a rare genetic disorder of the connective tissue. It presents with a wide spectrum of skeletal and extraskeletal features, and ranges in severity from mild to perinatal lethal. The disease is characterized by a heterogeneous genetic background, where approximately 85%-90% of cases have dominantly inherited heterozygous pathogenic variants located in the COL1A1 and COL1A2 genes. This paper presents the results of the first nationwide study, performed on a large cohort of 197 Polish OI patients. Variants were identified using a next-generation sequencing (NGS) custom gene panel and multiplex ligation probe amplification (MLPA) assay. The following OI types were observed: 1 (42%), 2 (3%), 3 (35%), and 4 (20%). Collagen type I pathogenic variants were reported in 108 families. Alterations were observed in α1 and α2 in 70% and 30% of cases, respectively. The presented paper reports 97 distinct causative variants and expands the OI database with 38 novel pathogenic changes. It also enabled the identification of the first glycine-to-tryptophan substitution in the COL1A1 gene and brought new insights into the clinical severity associated with variants localized in "lethal regions". Our results contribute to a better understanding of the clinical and genetic aspects of OI.

Inhibition Effect of Physalis angulata Leaf Extract on Viability, Collagen Type I, and Tissue Inhibitor of Metalloproteinase 1 (TIMP-1) but Not Plasminogen Activator Inhibitor-1 (PAI-1) of Keloid Fibroblast Culture.

Introduction: Keloids are excessive fibroproliferative diseases that are caused by abnormal wound healing. The anti-proliferative activity of Physalis angulata compounds has potential as a keloid therapeutic agent. This study aimed to observe the effects of P. angulata on fibroblast viability and collagen type I, tissue inhibitor of metalloproteinase 1 (TIMP-1), and plasminogen activator inhibitor 1 (PAI-1) levels in human keloid fibroblasts. Methods: We conducted an experimental study of P. angulata ethanol extract on three primary human keloid fibroblast 3 passage cultures with four replications. Fibroblast viability was measured using the MTT assay after incubation with 3, 5, and 10 µg/mL P. angulata. Concentrations of P. angulata used to observe effects on TIMP-1, PAI-1, and collagen type I levels were 10%, 20%, 30%, and 40% of inhibitory concentration 50 (IC50). The levels of collagen type I, TIMP-1, and PAI-1 were measured by ELISA. Mean comparisons between multiple treatment groups were analyzed using one-way ANOVA followed by post-hoc analysis. Results: The 10 µg/mL P. angulata group had significantly lower fibroblast viability than the control group (p<0.05) with an IC50 6.3 µg/mL. The collagen type I level of 10% IC50 (0.63 µg/mL) P. angulata group was lower than control (12.910 vs 47.866 ng/mL) (p=0.042). Level of TIMP-1 in 40% IC50 (2.51 µg/mL) P. angulata group was lower than control (5.350 vs 9.972 ng/mL) (p=0.043). There was no significant difference in the PAI-1 levels. Conclusion: This study showed the inhibitory effect of 10 µg/mL P. angulata extract on keloid fibroblast viability, with an IC50 of 6.3 µg/mL. This study also showed collagen type-1 and TIMP-1 inhibition, but not PAI-1 inhibition, after P. angulate treatment.

Urinary Peptidomics and Pulse Wave Velocity: The African-PREDICT Study.

Increased arterial stiffness is related to early vascular aging and is an independent predictor for cardiovascular disease and mortality. Molecular mechanisms underlying increased arterial stiffness are largely unexplored, especially at the proteome level. We aimed to explore the relationship between pulse wave velocity and urinary proteomics. We included 919 apparently healthy (no chronic illnesses) Black and White men and women (equally distributed) between 20 and 30 years from the African-PREDICT study. Capillary electrophoresis time-of-flight mass spectrometry was used to analyze the urinary proteome. We measured the carotid-femoral pulse wave velocity to estimate arterial stiffness. In the total group, pulse wave velocity correlated positively with collagen-derived peptides including collagen types I, II, III, IV, V, and IX and inversely with collagen type XI (adjusted for mean arterial pressure). Regarding noncollagen-derived peptides, pulse wave velocity positively correlated with polymeric immunoglobulin receptor peptides (n = 2) (all q-value ≤0.05). In multivariable adjusted analyses, pulse wave velocity associated positively and independently with seven urinary peptides (collagen type I, n = 5) (all p-value ≤0.05). We found significant positive and independent associations between pulse wave velocity and the collagen type I-derived peptides, suggesting that dysregulation of collagen type I in the extracellular matrix scaffold could lead to early onset of increased arterial stiffness.

Role of Collagen in the Etiology of Inguinal Hernia Patients: A Case-Control Study.

Introduction Technical faults are no longer accepted as the sole reason for recurrence following inguinal hernia (InH) repairs. Medical literature has been studied to find any contributing factors and collagen has emerged as a promising marker. Owing to their long half-lives, it has been found to best reflect the process of scarring, which is central to ensuring the formation of a proper fibrous tissue that incorporates the mesh with the abdominal wall. Methods Sixty participants were divided into two groups. The case group were patients diagnosed with InH and the control group had patients undergoing abdominal surgeries for indications other than abdominal wall hernias. A 0.5x0.5cm specimen of skin and transversalis fascia were biopsied and subsequently stained to determine the amount of collagen I and III. Results Collagen I, collagen III and the ratio of collagen I to III was measured. Collagen I was normal in the skin of both groups but decreased in transversalis fascia of cases. Collagen III was found to be normal in transversalis fascia of both cases and controls, but increased in the skin of cases. Ratio of collagen I to III was decreased in both skin and transversalis fascia of cases. Statistical analysis was carried out using an unpaired t-test, non-parametric Mann-Whitney test, ANOVA and chi-square test. Conclusions Our study has reported that in patients with inguinal hernia, collagen III or immature collagen is increased in skin and collagen I or mature collagen is decreased in the transversalis fascia. The ratio of collagen I/III is decreased in both skin and transversalis fascia.