Effect of poly-L-lactic acid and polydioxanone biostimulators on type I and III collagen biosynthesis.

OBJECTIVE: Safe, effective, and biocompatible minimally invasive procedures with the potential to stimulate collagen production have been made to recover dermal thickness and skin quality. The main of this animal model experiment was to observe the effect of poly-L-lactic acid (PLLA) and polydioxanone (PDO) biostimulators in collagen I and III after hypodermal injection. METHODOLOGY: Sixteen adult female rats (Wistar) were randomized into four groups and had dorsal treatment with: G1: hypodermic subcision (HS) only; G2: HS and PLLA hypodermic injection (HI), G3: HS and PDO HI; G4: Control, with no treatment. RESULTS: In histochemical, it was observed hypodermal and dermal tissue in more organized thickness in G3 and in G4 when compared to G1 and G2. There was few difference in G1 compared to G4. The tissue of G2 showed irregularities in the arrangement of collagen fibers, less defined structure and lower distribution of type I collagen compared to the other groups. There is a greater tendency for the proportions of type III collagen among tissues treated with both biostimulators (G2 and G3). PLLA and PDO had relatively similar percentages of collagen when compared to G4. The amount of type I collagen was higher in tissues treated with subcision, while type III collagen was higher in tissues treated with both biostimulators. CONCLUSION: G3 showed better performance in collagen production, although small, when compared with G2.

The Combined Anti-Aging Effect of Hydrolyzed Collagen Oligopeptides and Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells on Human Skin Fibroblasts.

Stem cell-derived exosomes (SC-Exos) are used as a source of regenerative medicine, but certain limitations hinder their uses. The effect of hydrolyzed collagen oligopeptides (HCOPs), a functional ingredient of SC-Exos is not widely known to the general public. We herein evaluated the combined anti-aging effects of HCOPs and exosomes derived from human umbilical cord mesenchymal stem cells (HucMSC-Exos) using a senescence model established on human skin fibroblasts (HSFs). This study discovered that cells treated with HucMSC-Exos + HCOPs enhanced their proliferative and migratory capabilities; reduced both reactive oxygen species production and senescence-associated ß-galactosidase activity; augmented type I and type III collagen expression; attenuated the expression of matrix-degrading metalloproteinases (MMP-1, MMP-3, and MMP-9), interleukin 1 beta (IL-1ß), and tumor necrosis factor-alpha (TNF-α); and decreased the expression of p16, p21, and p53 as compared with the cells treated with HucMSC-Exos or HCOPs alone. These results suggest a possible strategy for enhancing the skin anti-aging ability of HucMSC-Exos with HCOPs.

Deconvolution of synovial myeloid cell subsets across pathotypes and role of COL3A1+ macrophages in rheumatoid arthritis remission.

Background: Monocyte/macrophage (Mo/Mp) is a critical cell population involved in immune modulation of rheumatoid synovitis (RA) across different pathotypes. This study aims to investigate the contribution of Mo/Mp clusters to RA activity, and the biological function of particular subtypes in RA remission. Methods: We integrated single-cell RNA sequencing datasets from 4 published and 1 in-house studies using Liger selected by comparison. We estimated the abundance of Mo/Mp subtypes in bulk RNA-seq data from the 81 patients of the Pathobiology of Early Arthritis Cohort (PEAC) using deconvolution analysis. Correlations between Mo/Mp subtypes and RA clinical metrics were assessed. A particular cell type was identified using multicolor immunofluorescence and flow cytometry in vivo and successfully induced from a cell line in vitro. Potential immune modulation function of it was performed using immunohistochemical staining, adhesion assay, and RT-qPCR. Results: We identified 8 Mo/Mp clusters. As a particular subtype among them, COL3A1+ Mp (CD68+, COL3A1+, ACTA2-) enriched in myeloid pathotype and negatively correlated with RA severity metrics in all pathotypes. Flow cytometry and multicolor immunofluorescence evidenced the enrichment and M2-like phenotype of COL3A1+ Mp in the myeloid pathotype. Further assays suggested that COL3A1+ Mp potentially attenuates RA severity via expressing anti-inflammatory cytokines, enhancing Mp adhesion, and forming a physical barrier at the synovial lining. Conclusion: This study reported unexplored associations between different pathologies and myeloid cell subtypes. We also identified a fibroblast-and-M2-like cluster named COL3A1+ Mp, which potentially contributes to synovial immune homeostasis. Targeting the development of COL3A1+ Mp may hold promise for inducing RA remission.

Role and mechanism of COL3A1 in regulating the growth, metastasis, and drug sensitivity in cisplatin-resistant non-small cell lung cancer cells.

Non-small cell lung cancer (NSCLC) is among the most difficult malignancies to treat. Type III collagen (COL3A1) can affect the progression and chemoresistance development of NSCLC. We herein explored the mechanism that drives COL3A1 dysregulation in NSCLC. Potential RNA-binding proteins (RBPs) and transcription factors (TFs) that could bind to COL3A1 were searched by bioinformatics. mRNA expression was detected by quantitative PCR. Protein expression was evaluated using immunoblotting and immunohistochemistry. The effects of the variables were assessed by gauging cell growth, invasiveness, migratory capacity, apoptosis, and cisplatin (DDP) sensitivity. The direct YY1/COL3A1 relationship was confirmed by ChIP and luciferase reporter experiments. Xenograft experiments were done to examine COL3A1's function in DDP efficacy. COL3A1 showed enhanced expression in DDP-resistant NSCLC. In H460/DDP and A549/DDP cells, downregulation of COL3A1 exerted inhibitory functions in cell growth, invasiveness, and migration, as well as promoting effects on cell DDP sensitivity and apoptosis. Mechanistically, ELAV-like RNA binding protein 1 (ELAVL1) enhanced the mRNA stability and expression of COL3A1, and Yin Yang 1 (YY1) promoted the transcription and expression of COL3A1. Furthermore, upregulation of COL3A1 reversed ELAVL1 inhibition- or YY1 deficiency-mediated functions in DDP-resistant NSCLC cells. Additionally, COL3A1 downregulation enhanced the anti-tumor efficacy of DDP in vivo. Our investigation demonstrates that COL3A1 upregulation, induced by both RBP ELAVL1 and TF YY1, exerts important functions in phenotypes of NSCLC cells with DDP resistance, offering an innovative opportunity in the treatment of drug-resistant NSCLC.

Digital pathology with artificial intelligence analysis provides insight to the efficacy of anti-fibrotic compounds in human 3D MASH model.

Metabolic dysfunction-associated steatohepatitis (MASH) is a severe liver disease characterized by lipid accumulation, inflammation and fibrosis. The development of MASH therapies has been hindered by the lack of human translational models and limitations of analysis techniques for fibrosis. The MASH three-dimensional (3D) InSight™ human liver microtissue (hLiMT) model recapitulates pathophysiological features of the disease. We established an algorithm for automated phenotypic quantification of fibrosis of Sirius Red stained histology sections of MASH hLiMTs model using a digital pathology quantitative single-fiber artificial intelligence (AI) FibroNest™ image analysis platform. The FibroNest™ algorithm for MASH hLiMTs was validated using anti-fibrotic reference compounds with different therapeutic modalities-ALK5i and anti-TGF-ß antibody. The phenotypic quantification of fibrosis demonstrated that both reference compounds decreased the deposition of fibrillated collagens in alignment with effects on the secretion of pro-collagen type I/III, tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-3 and pro-fibrotic gene expression. In contrast, clinical compounds, Firsocostat and Selonsertib, alone and in combination showed strong anti-fibrotic effects on the deposition of collagen fibers, however less pronounced on the secretion of pro-fibrotic biomarkers. In summary, the phenotypic quantification of fibrosis of MASH hLiMTs combined with secretion of pro-fibrotic biomarkers and transcriptomics represents a promising drug discovery tool for assessing anti-fibrotic compounds.

Generation of the human induced pluripotent stem cell line (IBKMOLi003-A) from PBMCs of a vascular Ehlers-Danlos syndrome (vEDS) patient carrying the heterozygous nonsense mutation c.430C > T (p.Q105*) in the COL3A1 gene.

Ehlers-Danlos syndrome (EDS) belongs to a spectrum of rare heritable connective tissue disorders and is characterised by hyperextensibility, joint hypermobility and tissue fragility. Peripheral blood mononuclear cells (PBMCs) from a vascular EDS (vEDS) patient, known as the rarest EDS subtype, carrying a heterozygous nonsense mutation c.430C > T (p.Q105*) in the COL3A1 gene, which is essential for type III collagen synthesis, were reprogrammed into induced pluripotent stem cells (iPSCs). The generated iPSCs exhibit high expression of pluripotency-associated markers, possess trilineage differentiation capacity and reveal a normal karyotype. This novel patient-specific cell line enables in-depth pathophysiological studies of vEDS.

The relationship and diagnostic efficacy of N-terminal propeptide type III collagen in pathological changes associated with non-alcoholic steatohepatitis.

OBJECTIVE: This study delves into the role of N-terminal propeptide type III collagen (PIIINP) in the diagnosis and management of liver pathological changes associated with non-alcoholic steatohepatitis (NASH). PATIENTS AND METHODS: We collected baseline information, pathological data, and serum PIIINP levels of 168 patients diagnosed with non-alcoholic fatty liver disease (NAFLD) via ultrasound imaging in our hospital. Based on the non-alcoholic fatty liver disease activity score (NAS), patients with different NAFLD patterns were divided into a Definite NASH group and a Not/borderline group. Differences in PIIINP levels and pathological features between the two groups were compared and analyzed. The diagnostic value of PIIINP for NASH was evaluated using the receiver operating characteristic (ROC) curve. RESULTS: Patients with NASH exhibited significantly higher values of homeostatic model assessment for insulin resistance (HOMA-IR), fibrosis biomarker fibrosis-4 (FIB-4), aminotransferase-to-platelet ratio index (APRI), and serum PIIINP levels than those classified as Not/borderline. A marked increase in the serum concentrations of PIIINP was observed with the severity of fatty degeneration, lobular inflammation, and hepatocellular ballooning. The AUC of PIIINP for diagnosing definite NASH was 0.766 (95% CI: 0.694, 0.839), APRI was 0.634 (95% CI: 0.549, 0.718), and FIB-4 was 0.621 (95% CI: 0.534, 0.708). The AUC of PIIINP for diagnosing definite NASH was significantly higher than that of APRI and FIB-4 (all p<0.05). Utilizing the predetermined threshold values for diagnostic parameters, the PIIINP measure demonstrated a sensitivity of 71.6% and a specificity of 73.6% in diagnosing definitive NASH when its value exceeded 7.72 ng/dL. This yielded a Youden index of 0.45. Similarly, when the APRI measure exceeded 0.21, it exhibited a sensitivity of 60.5% and a specificity of 63.2%, resulting in a Youden index of 0.24. Moreover, when the FIB-4 index surpassed 0.26, it showed a sensitivity of 46.9% and a specificity of 79.3%, culminating in a Youden index of 0.26. CONCLUSIONS: NASH patients in this study exhibited significantly elevated PIIINP serum levels, which were closely associated with hepatocyte pathological changes. PIIINP demonstrated superior competence in diagnosing NASH than APRI and FIB-4 and thus offers a viable alternative for the clinical diagnosis of NASH.

Bioactive-Glass-Based Materials with Possible Application in Diabetic Wound Healing: A Systematic Review.

Diabetes affected 537 million adults in 2021, costing a total of USD 966 billion dollars in healthcare. One of the most common complications associated with diabetes corresponds to the development of diabetic foot ulcers (DFUs). DFUs affect around 15% of diabetic patients; these ulcers have impaired healing due to neuropathy, arterial disease, infection, and aberrant extracellular matrix (ECM) degradation, among other factors. The bioactive-glass-based materials discussed in this systematic review show promising results in accelerating diabetic wound healing. It can be concluded that the addition of BG is extremely valuable with regard to the wound healing rate and wound healing quality, since BG activates fibroblasts, enhances M1-to-M2 phenotype switching, induces angiogenesis, and initiates the formation of granulation tissue and re-epithelization of the wound. In addition, a higher density and deposition and better organization of collagen type III are seen. This systematic review was made using the PRISMA guideline and intends to contribute to the advancement of diabetic wound healing therapeutic strategies development by providing an overview of the materials currently being developed and their effect in diabetic wound healing in vitro and in vivo.

Molecular mechanisms of pelvic organ prolapse influenced by FBLN5 via FOSL1/miR-222/MEIS1/COL3A1 axis.

This study delves into the role of FBLN5 in pelvic organ prolapse (POP) and its molecular mechanisms, focusing on the FOSL1/miR-222/MEIS1/COL3A1 axis. Gene relationships linked to POP were confirmed using bioinformatics databases like GEO and StarBase. Primary human uterosacral ligament fibroblasts (hUSLF) were extracted and subjected to mechanical stretching. Cellular cytoskeletal changes were examined via phalloidin staining, intracellular ROS levels with a ROS kit, cell apoptosis through flow cytometry, and cell senescence using ß-galactosidase staining. FBLN5's downstream targets were identified, and the interaction between FOSL1 and miR-222 and miR-222 and MEIS1 were validated using assays. In rat models, the role of FBLN5 in POP was assessed using bladder pressure tests. Results indicated diminished FBLN5 expression in uterine prolapse. Enhanced FBLN5 countered mechanical damage in hUSLF cells by downregulating FOSL1. FOSL1 augmented miR-222, inhibiting MEIS1, which subsequently fostered COL3A1 transcription. In rat models, the absence of FBLN5 exacerbated POP by influencing the FOSL1/miR-222/MEIS1/COL3A1 pathway. FBLN5's protective role likely involves regulating the above axis and boosting COL3A1 expression. Further research is needed to validate the effectiveness and safety of this mechanism in human patients and to propose potential new treatment options.

Collagen induction of immune cells in the mammary glands during pregnancy.

The mammary glands are dynamic tissues affected by pregnancy-related hormones during the pregnancy-lactation cycle. Collagen production and its dynamics are essential to the remodeling of the mammary glands. Alterations of the mammary microenvironment and stromal cells during the pregnancy-lactation cycle are important for understanding the physiology of the mammary glands and the development of breast tumors. In this study, we performed an evaluation of collagen dynamics in the mammary fat pad during the pregnancy-lactation cycle. Reanalysis of single-cell RNA-sequencing (scRNA-Seq) data showed the ectopic collagen expression in the immune cells and cell-cell interactions for collagens with single-cell resolution. The scRNA-Seq data showed that type I and type III collagen were produced not only by stromal fibroblasts but also by lymphoid and myeloid cell types in the pregnancy phase. Furthermore, the total cell-cell interaction score for collagen interactions was dramatically increased in the pregnancy tissue. The data presented in this study provide evidence that immune cells contribute, at least in part, to mammary collagen dynamics. Our findings suggest that immune cells, including lymphoid and myeloid cells, might be supportive members of the extracellular matrix orchestration in the pregnancy-lactation cycle of the mammary glands.NEW & NOTEWORTHY Our study evaluated mammary gland collagen dynamics during the pregnancy-lactation cycle using single-cell RNA-sequencing data. We found ectopic collagen expression in immune cells and an increase in collagen interactions during pregnancy. Type I and type III collagen were produced by lymphoid, myeloid, and stromal fibroblast cells during pregnancy. These findings suggest that immune cells, including lymphoid and myeloid cells, play a crucial role in supporting the extracellular matrix in mammary glands during pregnancy-lactation cycles.

Study on the Effect of Type III Recombinant Humanized Collagen on Human Vascular Endothelial Cells.

The effect and mechanism of type III recombinant humanized collagen (hCOLIII) on human vascular endothelial EA.hy926 cells at the cellular and molecular levels were investigated. The impact of hCOLIII on the proliferation of EA.hy926 cells was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid assay, the effect of hCOLIII on cell migration was investigated by scratch assay, the impact of hCOLIII on cell cycle and apoptosis was detected by flow cytometry, the ability of hCOLIII to induce angiogenesis of EA.hy926 cells was evaluated by angiogenesis assay, and the effect of hCOLIII on vascular endothelial growth factor (VEGF) expression was detected by real-time reverse transcription-polymerase chain reaction analysis. The hCOLIII at concentrations of 0.5, 0.25, and 0.125 mg/mL all showed specific effects on the proliferation and migration of human vascular endothelial cells. It could also affect the cell cycle, increase the proliferation index, and increase the expression level of VEGF in human vascular endothelial cells. In the meantime, hCOLIII at the concentration of 0.5 mg/mL also showed a promoting effect on vessel formation. hCOLIII can potentially promote the endothelization process of blood vessels, mainly by affecting the proliferation, migration, and vascular-like structure of human endothelial cells. At the same time, hCOLIII can promote the expression of VEGF. This collagen demonstrated its potential as a raw material for cardiovascular implants.

Muscle quality, physical performance, and comorbidity are predicted by circulating procollagen type III N-terminal peptide (P3NP): the InCHIANTI follow-up study.

Sarcopenia is characterized by skeletal muscle quantitative and qualitative alterations. A marker of collagen turnover, procollagen type III N-terminal peptide (P3NP), seems to be related to those conditions. This study aims to assess the predictive role of P3NP in muscle density and physical performance changes. In the InCHIANTI study, a representative sample from the registry lists of two towns in Tuscany, Italy, was recruited. Baseline data was collected in 1998, and follow-up visits were conducted every 3 years. Out of the 1453 participants enrolled at baseline, this study includes 1052 participants. According to P3NP median levels, population was clustered in two groups; 544 (51.7%) of the 1052 subjects included were classified in the low median levels (LM-P3NP); at the baseline, they were younger, had higher muscle density, and performed better at the Short Physical Performance Battery (SPPB), compared to the high-median group (HM-P3NP).LM-P3NP cases showed a lower risk to develop liver chronic diseases, CHF, myocardial infarction, and osteoarthritis. HM-P3NP levels were associated with a longitudinal reduction of muscle density, and this effect was potentiated by the interaction between P3NP and leptin. Moreover, variation in physical performance was inversely associated with high level of P3NP, and directly associated with high fat mass, and with the interaction between P3NP and muscle density. Our data indicate that P3NP is associated with the aging process, affecting body composition, physical performance, and clinical manifestations of chronic degenerative age-related diseases.

RNF185 Control of COL3A1 Expression Limits Prostate Cancer Migration and Metastatic Potential.

RNF185 is a RING finger domain-containing ubiquitin ligase implicated in ER-associated degradation. Prostate tumor patient data analysis revealed a negative correlation between RNF185 expression and prostate cancer progression and metastasis. Likewise, several prostate cancer cell lines exhibited greater migration and invasion capabilities in culture upon RNF185 depletion. Subcutaneous inoculation of mouse prostate cancer MPC3 cells stably expressing short hairpin RNA against RNF185 into mice resulted in larger tumors and more frequent lung metastases. RNA-sequencing and Ingenuity Pathway Analysis identified wound-healing and cellular movement among the most significant pathways upregulated in RNF185-depleted lines, compared with control prostate cancer cells. Gene Set Enrichment Analyses performed in samples from patients harboring low RNF185 expression and in RNF185-depleted lines confirmed the deregulation of genes implicated in epithelial-to-mesenchymal transition. Among those, COL3A1 was identified as the primary mediator of RNF185's ability to impact migration phenotypes. Correspondingly, enhanced migration and metastasis of RNF185 knockdown (KD) prostate cancer cells were attenuated upon co-inhibition of COL3A1. Our results identify RNF185 as a gatekeeper of prostate cancer metastasis, partly via its control of COL3A1 availability. IMPLICATIONS: RNF185 is identified as an important regulator of prostate cancer migration and metastasis, in part due to its regulation of COL3A1. Both RNF185 and COL3A1 may serve as novel markers for prostate tumors.

COL3A1-positive endothelial cells influence LUAD prognosis and regulate LUAD carcinogenesis by NCL-PI3K-AKT axis.

BACKGROUND: Lung adenocarcinoma (LUAD), as the most common type of lung cancer, poses a significant threat to public health. Tumor heterogeneity plays a crucial role in carcinogenesis, which could be largely deciphered by next-generation sequencing (NGS). METHODS: We obtained and screened single-cell RNA sequencing (scRNA-seq) data from 16 LUAD samples, and endothelial cells (ECs) were grouped into three clusters. The origin of EC differentiation was explored by pseudo-time analysis. CellChat analysis was used to detect potential communication between ECs and malignant cells, and gene regulatory network analysis was used to identify changes in transcription factor activity. We explored the prognosis of specific ECs clusters and their effects on the tumor microenvironment (TME) at the bulk transcriptome level. 5-Ethynyl-2'- deoxyuridine (EdU) and Ki-67 staining were conducted to study the proliferative phenotype of LUAD cell lines. Western blotting targeting the phosphorylation of PI3K-AKT proteins was utilized for determination of the downstream pathway of NCL. RESULTS: COL3A1-positive ECs showed the highest crosstalk interaction with malignant cells, indicating that they have important effects on driving LUAD carcinogenesis. Vascular endothelial growth factor (VEGF) signaling pathway was identified as the main signaling pathway, mediating signal transduction from malignant cells. The TME-related genes of COL3A1-positive ECs were significantly more highly expressed. COL3A1-positive ECs showed unique metabolic and immune characteristics, as well as highly activated metabolic signaling pathways and inflammatory responses. Importantly, LUAD patients with low COL3A1-positive ECs scores displayed an inferior prognosis outcome and a higher risk of metastasis. The key target gene NCL, which is involved in the interaction between epithelial cells and cancer cells, has been identified through screening. Flow cytometry showed that knockdown of NCL prompted the apoptosis of A549 and NCI-H1299. Western blotting showed that knockdown of NCL decreased the phosphorylation of AKT and PI3K, which identified the downstream pathway of NCL. CONCLUSIONS: COL3A1-positive ECs have important effects on the development of LUAD and the formation of an immune microenvironment. Furthermore, we identified a key target gene, NCL, which is involved in the interaction between endothelial cells and cancer cells. NCL also affected the apoptosis and proliferation in LUAD through the PI3K-AKT pathway.

Chitosan thread in the healing of the cecal wall of rabbits (Oryctolagus cuniculus) submitted to cecorrhaphy.

The development and evaluation of synthesis materials are crucial to reducing the morbidity and magnitude of post-enterorrhaphy surgical complications. Despite the possibility of production, chitosan thread has not yet been used in enterorrhaphy, and its effects on intestinal healing have not been evaluated. Therefore, this study aimed to evaluate the effects of chitosan thread on the intestinal wall repair of rabbits submitted to cecorrhaphy. For this, 42 rabbits were allocated into two groups with 21 animals. One group was submitted to cecorrhaphy with chitosan suture thread (CG) and the other with poliglecaprone suture thread (PG). The occurrence of postoperative complications, the intensity of edema, cellular response, formation of granulation tissue, as well as the deposition and maturation of collagen fibers, and the intensity of vascular endothelial growth factor (VEGF-α) expression, were evaluated during the intestinal wall repair process. The evaluations occurred on the 5th, 15th, and 25th postoperative (PO) days. The animals did not develop peritonitis, but adherence was observed in six animals from CG and seven from PG, with no difference between groups. The polymorphonuclear infiltrate showed higher intensity and higher amount of type III collagen fibers in CG on the 15th PO day. In contrast, a lower amount of type I collagen fibers was observed in CG samples on the 25th PO day. Therefore, the chitosan thread used for cecorrhaphy in rabbits results in minimal postoperative complications, presents biocompatibility, and bioactively assists the tissue repair process of the cecal wall, inducing minimal tissue reaction, stimulating the deposition of type III collagen fibers in the proliferative phase, with sustained VEGF-α expression, but with reduced deposition of type I fibers, indicating a delay in collagen maturation.

COL3A1 is a potential diagnostic biomarker for synovial chondromatosis and affects the cell cycle and migration of chondrocytes.

BACKGROUND: Synovial chondromatosis (SC) primarily affects the major joints and is characterized by the formation of benign cartilaginous nodules. In the present study, we evaluated the differences in the histology and gene expression of SC and normal cartilages and further elucidated the function of hub genes in SC. METHODS: Histological staining and biochemical analysis were performed to measure collagen and glycosaminoglycan (GAG) contents in SC and normal cartilage samples. Then, microarray analysis was performed using knee joint samples (three normal and three SC samples) to identify the differentially expressed genes (DEGs). Subsequently, bioinformatics analysis was performed to identify the hub genes and explore the mechanisms underlying SC. The intersection of the top 10 upregulated DEGs, top 10 downregulated DEGs, and hub genes was validated in SC tissues. Lastly, in vitro experiments and our clinical cohort were used to determine the potential biological functions and diagnostic value, respectively, of the most significant gene. RESULTS: The GAG and collagen contents were comparable to or higher in SC tissues than in normal tissues. Microarray analysis revealed 143 upregulated and 107 downregulated DEGs in SC. Furthermore, functional enrichment analysis revealed an association between immunity and metabolism-related pathways and SC development. Among 20 hub genes, two intersection genes, namely, collagen type III alpha 1 chain (COL3A1) and HSPA8, were notably expressed in SC tissues, with COL3A1 exhibiting a more significant difference in mRNA expression. Furthermore, COL3A1 can promote chondrocyte migration and cell cycle progression. Additionally, clinical data revealed COL3A1 can be a diagnostic marker for primary SC (AUC = 0.82) and be a positive correlation with neutrophil-to-lymphocyte ratio. CONCLUSIONS: These results suggest that SC tissues contained the abundant GAG and collagen. COL3A1 can affect the function of chondrocytes and be a diagnostic marker of primary SC patients. These findings provide a novel approach and a fundamental contribution for diagnosis and treatment in SC.

Plasma levels of PRO-C3, a type III collagen synthesis marker, are associated with arterial stiffness and increased risk of cardiovascular death.

BACKGROUND AND AIMS: The N-terminal propeptide of type III collagen (PRO-C3) assay measures a pro-peptide released during type III collagen synthesis, an important feature of arterial stiffening and atherogenesis. There is a clinical need for improved non-invasive, cheap and easily accessible methods for evaluating individuals at risk of cardiovascular disease (CVD). In this study, we investigate the potential of using circulating levels of PRO-C3 to mark the degree of vascular stenosis and risk of cardiovascular events. METHODS: Baseline plasma levels of PRO-C3 were measured by ELISA in subjects belonging to the SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) cohort (N = 1354). Associations between PRO-C3 levels with vascular characteristics, namely stiffness and stenosis, and risk of future cardiovascular events were explored. Subjects were followed up after a median of 35 months (interquartile range 34-36 months), with recorded outcomes cardiovascular death and all-cause mortality. RESULTS: We found a correlation between PRO-C3 levels and pulse wave velocity (rho 0.13, p = 0.000009), a measurement of arterial stiffness. Higher PRO-C3 levels were also associated with elevated blood pressure (rho 0.07, p = 0.014), as well as risk of cardiovascular mortality over a three-year follow-up period (OR 1.56, confidence interval 1.008-2.43, p = 0.046). CONCLUSIONS: Elevated circulating PRO-C3 levels are associated with arterial stiffness and future cardiovascular death, in the SUMMIT cohort, suggesting a potential value of PRO-C3 as a novel marker for declining vascular health.

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.

A Modified Suture Technique to Improve Scar Appearance in Wounds Under High Tension.

ABSTRACT: The purpose of this study was to introduce a modified suture technique and to compare its effects on skin scar formation with 2 traditional suture methods: simple interrupted suture (SIS) and vertical mattress suture (VMS). Three groups of healthy adult female Sprague-Dawley rats were selected (6 replicates in each group), and the full-thickness skin of 5 cm × 0.2 cm was cut off on the back of the rats after anesthesia. The wounds were then sutured using 1 of the 3 methods for each group: SIS, VMS, and a newly introduced modified vertical mattress suture (M-VMS) technique with the needle reinsertion at the exit point. A traction device was installed on the back of the rats to achieve high tension wounds. The tensile distance was increased by 1 mm every day for 20 days. After 20 days of healing, the hematoxylin-eosin staining method was used for observation of scar morphology. The collagen production rate was measured by Masson staining, and the type I collagen and type III collagen were detected by the immunofluorescence method. Immunohistochemical staining was used to detect the expression of myofibroblast marker α-smooth muscle actin, and real-time quantitative polymerase chain reaction and Western blot techniques were used to detect the expressions of transforming growth factors TGFß1, TGFß2, and TGFß3 to understand the mechanisms of scar formation. Results showed that the quantity and density of collagen fibers were both lower in the M-VMS group than in the other 2 groups. Immunofluorescence results showed that type I collagen was significantly lower, whereas type III collagen was significantly higher in the M-VMS group than in the other 2 groups. The expressions of α-smooth muscle actin and TGFß1 both were lower in the M-VMS group than in the other 2 groups. The expression of TGFß2 and TGFß3 had no obvious difference among the 3 groups. For wounds under high tension, compared with SIS and VMS methods, the M-VMS technique we proposed can reduce scar formation due to the reduction of collagen formation, myofibroblast expression, and TGFß1 expression.

Bioinformatic Analysis of the Mechanism of Action of COL3A1 in Pan-Cancer and Design of Specific Inhibitors for Its Conformation.

In this study, we investigated the mechanism of action of COL3A1 in various types of cancers by bioinformatics analysis and designed some specific inhibitors aimed at the treatment of this gene. We found that COL3A1 was highly expressed in several cancer types and correlated with tumor progression and prognosis. Through systems biology analysis, we identified a central role for COL3A1 in cancer development, including cell proliferation, metastasis and invasion. We also used molecular dynamics simulations and drug screening techniques to design anticancer drugs with potential COL3A1 inhibitory functions. These results provide a strong rationale for the development and use of COL3A1 as a therapeutic target.