Silencing of cysteine and serine rich nuclear protein 1 inhibits apoptosis, senescence and collagen degradation in human-derived vaginal fibroblasts in response to oxidative stress or DNA damage.

Pelvic organ prolapse (POP) is a group of diseases caused by extracellular matrix (ECM) degradation in pelvic supportive tissues. Cysteine and serine rich nuclear protein 1 (CSRNP1) is involved in cell proliferation and survival regulation, and reportedly facilitates collagen breakdown in human chondrocytes. The present study aimed to probe the effect of CSRNP1 on collagen metabolism in human-derived vaginal fibroblasts. High expression of CSRNP1 was found in POP patient-derived vaginal fibroblasts in comparison to normal-derived vaginal fibroblasts. Following functional experiments revealed that CSRNP1 overexpression led to proliferation inhibition, apoptosis and collagen degradation in normal vaginal fibroblasts. In line with this, silencing of CSRNP1 inhibited hydrogen peroxide (H2O2)-triggered apoptosis, ROS generation and collagen loss in normal vaginal fibroblasts. Silencing of CSRNP1 also reduced the expression of cell senescence markers p21 and γ-H2Ax (the histone H2Ax phosphorylated at Ser139), as well as curbed collagen breakdown in normal vaginal fibroblasts caused by a DNA damage agent etoposide. Transcriptomic analysis of vaginal fibroblasts showed that differentially expressed genes affected by CSRNP1 overexpression were mainly enriched in the Wnt signaling pathway. Treatment with a Wnt pathway inhibitor DKK1 blocked CSRNP1 knockdown-caused collagen deposition. Mechanistically, CSRNP1 was identified to be a target of Snail family transcriptional repressor 2 (SNAI2). Forced expression of CSRNP1 reversed the anti-apoptotic, anti-senescent and anti-collagen loss effects of SNAI2 in normal vaginal fibroblasts exposed to H2O2 or etoposide. Our study indicates that the SNAI2/CSRNP1 axis may be a key driver in POP progression, which provides a potential therapeutic strategy for POP.

Prediction of Clinically Significant Prostate Cancer by a Specific Collagen-related Transcriptome, Proteome, and Urinome Signature.

BACKGROUND AND OBJECTIVE: While collagen density has been associated with poor outcomes in various cancers, its role in prostate cancer (PCa) remains elusive. Our aim was to analyze collagen-related transcriptomic, proteomic, and urinome alterations in the context of detection of clinically significant PCa (csPCa, International Society of Urological Pathology [ISUP] grade group ≥2). METHODS: Comprehensive analyses for PCa transcriptome (n = 1393), proteome (n = 104), and urinome (n = 923) data sets focused on 55 collagen-related genes. Investigation of the cellular source of collagen-related transcripts via single-cell RNA sequencing was conducted. Statistical evaluations, clustering, and machine learning models were used for data analysis to identify csPCa signatures. KEY FINDINGS AND LIMITATIONS: Differential expression of 30 of 55 collagen-related genes and 34 proteins was confirmed in csPCa in comparison to benign prostate tissue or ISUP 1 cancer. A collagen-high cancer cluster exhibited distinct cellular and molecular characteristics, including fibroblast and endothelial cell infiltration, intense extracellular matrix turnover, and enhanced growth factor and inflammatory signaling. Robust collagen-based machine learning models were established to identify csPCa. The models outcompeted prostate-specific antigen (PSA) and age, showing comparable performance to multiparametric magnetic resonance imaging (mpMRI) in predicting csPCa. Of note, the urinome-based collagen model identified four of five csPCa cases among patients with Prostate Imaging-Reporting and Data System (PI-IRADS) 3 lesions, for which the presence of csPCa is considered equivocal. The retrospective character of the study is a limitation. CONCLUSIONS AND CLINICAL IMPLICATIONS: Collagen-related transcriptome, proteome, and urinome signatures exhibited superior accuracy in detecting csPCa in comparison to PSA and age. The collagen signatures, especially in cases of ambiguous lesions on mpMRI, successfully identified csPCa and could potentially reduce unnecessary biopsies. The urinome-based collagen signature represents a promising liquid biopsy tool that requires prospective evaluation to improve the potential of this collagen-based approach to enhance diagnostic precision in PCa for risk stratification and guiding personalized interventions. PATIENT SUMMARY: In our study, collagen-related alterations in tissue, and urine were able to predict the presence of clinically significant prostate cancer at primary diagnosis.

Dietary intake and glutamine-serine metabolism control pathologic vascular stiffness.

Perivascular collagen deposition by activated fibroblasts promotes vascular stiffening and drives cardiovascular diseases such as pulmonary hypertension (PH). Whether and how vascular fibroblasts rewire their metabolism to sustain collagen biosynthesis remains unknown. Here, we found that inflammation, hypoxia, and mechanical stress converge on activating the transcriptional coactivators YAP and TAZ (WWTR1) in pulmonary arterial adventitial fibroblasts (PAAFs). Consequently, YAP and TAZ drive glutamine and serine catabolism to sustain proline and glycine anabolism and promote collagen biosynthesis. Pharmacologic or dietary intervention on proline and glycine anabolic demand decreases vascular stiffening and improves cardiovascular function in PH rodent models. By identifying the limiting metabolic pathways for vascular collagen biosynthesis, our findings provide guidance for incorporating metabolic and dietary interventions for treating cardiopulmonary vascular disease.

Corneal crosslinking efficacy in patients with keratoconus under 18 years of age / Eficácia do crosslinking corneano em portadores de ceratocone com idade inferior a 18 anos

ABSTRACT Purpose: Keratoconus presents certain specificities in pediatric patients compared with adults. The greatest challenge is because the disease is typically more severe and progresses faster in children. This retrospective study aimed to report crosslinking procedure in patients under 18 years of age and their follow-up for at least 24 months after the procedure. Methods: Overall, 12 eyes from 10 patients were studied and data, such as visual acuity with and without correction, maximum keratometry, corneal thickness, foveal thickness, and endothelial microscopy, were assessed at both preoperative and postoperative visits. Corneal crosslinking was performed in all patients. Results: A tendency toward reduced Kmax and improved Corrected Distance Visual Acuity at all postoperative moments. Only one of the 12 eyes exhibited increased Kmax of more than 1 D during a time frame longer than 12 months. Regarding pachymetry, a tendency for corneal thinning was observed in the first four months after surgery. Conclusion: Encouraging results were obtained regarding the stabilization of the disease, progression, and procedural safety, corroborating to other authors' findings. The significance of early diagnosis and short-term follow-up were highlighted.

RESUMO Objetivo: O ceratocone na população pediátrica apresenta algumas particularidades em relação à população adulta. O maior desafio é devido à doença ser geralmente mais severa e rapidamente progressiva em crianças. Métodos: Este artigo utiliza uma análise retrospectiva para relatar o uso do crosslinking em jovens menores de 18 anos e sua evolução pelo menos 24 meses após o procedimento. Foram estudados 12 olhos de 10 pacientes, e dados como acuidade visual com e sem correção, ceratometria máxima, espessura corneana, espessura foveal e microscopia endotelial avaliados no pré e pós-operatórios. O crosslinking corneano foi realizado em todos os pacientes pelo mesmo cirurgião. Resultados: Observou-se uma tendência de redução do valor do Kmax e melhora da acuidade visual corrigida em todos os momentos de pós operatório. Com relação à paquimetria, observou-se afinamento corneano do ponto mais fino, nos primeiros quatro meses de pós-operatório. Conclusão: Resultados encorajadores foram obtidos com relação à estabilização da doença, progressão e segurança do procedimento, corroborando com as conclusões de outros autores. A importância do diagnóstico precoce e do acompanhamento a curto prazo do paciente deve ser destacada.

Role of Collagen Metabolism in Liver Fibrosis and Research Progress in Traditional Chinese Medicine on the Regulation of Collagen Metabolism / 中国药师

The abnormal accumulation of extracellular matrix (ECM) in liver is the main feature of hepatic fibrosis,and collagen is the most important component in ECM.Collagen plays an important role in the occurrence and development of liver fibrosis.Therefore,to find traditional Chinese medicine with significant effect on collagen metabolism has become a critical approach for the treatment of hepatic fibrosis.This review summarized the role of collagen metabolism in liver fibrosis,and the research progress in traditional Chinese medicines with anti-hepatic fibrosis effect by regulating collagen metabolism was explored as well.

Effects of water extract from Ligustri Lucidi Fructus on bone structure and metabolism in ovariectomized rats / 中草药

Objective: To investigate the protecting and regulatory effects of water extract from Fructus Ligustri Lucidi (FLL) on bone structure and bone metabolism in osteoporosis rats. Methods: SD female rats were bilaterally ovariectomized to establish osteoporosis model, and Sham operated rats only cut the fat around the ovary. Experimental rats were divided into four groups: Sham operation (SHAM) group, model (OVX) group, alendronic acid sodium (ALN) group, and Fructus Ligustri Lucidi (FLL) group, with nine rats in each group. The rats in FLL group were given FLL water extract (3.5 g/kg) and rats in ALL group were given ALN suspension (0.12 g/kg) by ig administration for 12 weeks. At the end of the experiments, the contents of serum and urine calcium (S-Ca) and phosphorus (S-P), urine creatinine (U-Ca/Cr and U-P/Cr), serum high density lipoprotein (HDL-C) cholesterol, low density lipoprotein (LDL-C) cholesterol, total cholesterol (TC), and triglyceride (TG) were measured by biochemical methods. The levels of collagen I amino terminal peptide (PINP), collagen I carboxyl terminal peptide (CTX-I), osteocalcin (OCN), and urine deoxypyridinoline (DPD) were measured with ELISA. The determination of alkaline phosphatase (ALP) was by radioimmunoassay method. To evaluate the change of bone tissue structure, the bone density instrument, VivaCT, and a universal testing machine were used. Results: FLL could inhibit the increased body weight of ovariectomy (OVX) rats, increase S-Ca, S-P, serum HDL and PINP contents, reduce urinary U-Ca/Cr and U-P/Cr ratios, reduce serum LDL-C, TC, TG, ALP, OCN, CTX, and reduce urinary DPD content (P < 0.05 or 0.01) in OVX rats. Meanwhile, FLL can elevate the femur head and vertebral bone mineral density, bone micro-structure and bone strength in OVX rats. Conclusion: FLL can improve the bone density and bone strength in OVX rats by regulating Ca and P metabolism, collagen and non-collagen metabolism.

Early clinical outcomes of laser in situ keratomileusis concurrent with accelerated corneal collagen crosslinking for myopia and astigmatism with thin cornea / 中华实验眼科杂志

Background Keratectasia after laser in situ keratomileusis (LASIK) is a rare but severe complication,which threatens the visual acuity and corneal strength.Corneal collagen crosslinking (CXL) is a new therapy that increases the security and decreases the risk of complication.However,the effectiveness and safety of LASIK-CXL is still need to be concerned.Objective This study was to evaluate the safety of LASIK-CXL for myopia and astigmatism with thin cornea.Methods A prospective cohort study was designed.A total of 128 eyes of 64 patients with thin corneal and myopic astigmatism enrolled in Beijing Tongren Eye Center from January 2014 to January 2015.The patients were assigned to LASIK group (74 eyes of 37 patients) and LASIK-CXL group (54 eyes of 27 patients).Refractive surgery was performed by Visumax femtosecond lasrer and VISX S4 excimer laser.Eyes of LASIK-CXL group applied accelerated CXL immediately after LASIK.The follow-up was 6 months.Manifest refraction,uncorrected (UDVA) and corrected distance visual acuity (CDVA),average keratometry values (AveK),anterior segment OCT (AS-OCT),corneal hysteresis (CH) and corneal resistance factor (CRF) were examined before and after operation.This research passed through Ethics Committee of Beijing Tongren Hospital.Results The spherical equivalent (SE) of the LASIK group and LASIK-CXL group were (-6.49 ±2.41)D and (-6.97 ±2.41) D before operation and decreased to (-0.68 ±0.88) D and (-0.75 ±0.94) D 6 months after operation.The UDVA (LogMAR) was 1.18±0.28 and 1.05±0.38 before operation and elevated to-0.06±0.09 and-0.03±0.186 months after operation in the LASIK group and LASIK-CXL group.The preoperative AveK values were (44.37 ±1.46) D and (44.47± 1.50)D in the LASIK group and LASIK-CXL group and reduced to postoperative (39.30±2.06) D and (38.66± 1.80) D.The preoperative SRI of LASIK group and LASIK-CXL group were 0.25 ±0.21 and 0.24±0.22,which increased to 0.29±0.24 and 0.28±0.24.The SAI values were 0.36±0.16 and 0.39±0.15 before operation,which increased to 0.57 ±0.31 and 0.75 ±0.376 months after operation,and the SAI value of the LASIK-CXL group was significantly higher than that of LASIK (F =10.220,P--0.002).CRF values of LASIK and LASIK-CXL were (8.44±1.44)mmHg and (8.63±1.35) mmHg in preoperation,which decreased to (5.74±1.31) mmHg and (6.25± 1.24) mmHg in postoperation.The result of LASIK-CXL was higher than that of LASIK (F=8.650,P =0.040).CH values were 8.78 ± 1.51 and 8.69 ± 1.62 in preoperation,which decreased to (7.23 ± 1.08) mmHg and (6.50±1.32)mmHg.The value of LASIK-CXL was lower than that of LASIK (F =5.860,P =0.017).The mean depth of demarcation line was (228.45±28.24) μm (range 165 to 310 μm) on OCT,which was presented in 45 eyes (81.82％) at 1 month in postoperation.Conclusions Accelerated CXL with FS-LASIK is effective and safe in improving visual acuity in myopic astigmatism patients with thin cornea,which also can increase the rigidity of the cornea.

Effects of embryonic fibroblasts on the aging-related phenotypes and dysfunction of diabetic ulcer fibro-blasts / 中华内分泌外科杂志

Objective To observe the effects of human embryonic fibroblasts ( FBs ) on the biological characteristics of diabetic FBs in vitro , and to explore the possible therapeutic mechanism on diabetic ulcers . Methods Diabetic FBs were isolated and cultured with embryonic FBs (experimental group), adult FBs(control group 1)and alone(control group 2)in transwell chambers.Diabetic FBs growth curves in the coculture systems were described.The cell shape was observed by microscopy with HE staining .On the 4th and 7th day of cocul-ture, diabetic FBs were isolated to measure the expression levels of hydroxyproline and transforming growth factor -beta 1(TGF-β1)in the supernatant of monoculture .The cell senescense was displayed by β-galactosidase histo-chemical staining on the 3th, 5th and 7th day of coculture.Eight patients with diabetic foot ulcers who were can-didates for embryonic FBs constructs after failed traditional treatment were included in the study .The pre and post self-control study was conducted by observing the wound healing process before and after embryonic FBs treat -ment.Results Diabetic FBs in the experimental coculture system displayed more typical pattern and faster grow -ing rate.The level of hydroxyproline and TGF-β1 in the supernatant of diabetic FBs monoculture was significantly higher in the experimental group than in the control group after treated 4 or 7 days ( hydroxyproline:4 d, 7 d :compared with control group 1:P=0.023,P=0.007;compared with control group 2: P=0.007, P=0.003;TGF-β1 4 d, 7 d:compared with control group 1:P=0.000, P=0.000;compared with control group 2: P=0.000, P=0.000).The expression of SA-β-gal tended to be more apparent in control group 1 and 2 than in the experimental group on the 3rd,5th,and 7th day.All of the 8 cases with diabetic ulcers were cured by using em-bryonic FBs constructs .Conclusion Embryonic FBs can promote the proliferation of diabetic FBs , correct cell senescence and increase the production of hydroxyproline and TGF-β1,which maybe enhance the process of dia-betic wound healing .

Effect of Aldosterone on the Proliferation and Collagen Metabolism of Cardiac Fibroblasts in Neonate Rat / 中国药房

OBJECTIVE: To investigate the effects of aldosterone (Ald) on the proliferation and collagen synthesis of cardiac fibroblasts (CFs) in neonate rats and to research its mechanism. METHODS: The neonatal rat cardiac fibroblasts were induced by anchorage velocity-dependent separation method. SD rats were divided into control group, Ald (1.0?10-7 mol?L-1) group, Ald combined with spirolactone group and Ald combined with losartan group. After 24 h of exposure, CFs proliferation was measured by MTT assay and cell cycle distribution was determined with flow cytometer (FCM). Spectrophotography was used to detect the content of hydroxyproline and immunofluorescence staining method was applied to determine the protein expression of proliferation cell nuclear antigen (PCNA) and fibronectin (FN). RESULTS: As compared with control group, in Ald group the activity of CFs was increased as well as its percentage in S stage. The content of hydroxyproline and the protein expression of PCNA and FN were also increased while the percentage of CFs in G0/G1 stage was decreased (P0.05). CONCLUSION: Ald-stimulated CFs proliferation and collagen synthesis were mediated by activation of AT1 receptors and Ald receptor,and Ald receptor plays a major role. A corresponding increase in the protein expression of PCNA and FN in CFs may be related to the proliferation effect.

Lipoid Proteinosis / 대한피부과학회지

Lipoid proteinosis is a rare autosomal recessively inherited disorder that is characterized by the deposition of hyaline-like material in the skin, oral cavity, and other organs. Microscopically, there is extensive deposition of amorphous eosinophilic material surrounding capillaries, sweat glands and in papillary dermis. Although the pathogenesis of this disease is not well understood, it is believed that it may result from the defect of collagen metabolism leading to abnormal accumulation of noncollagenous glycoprotein. We report a case of lipoid proteinosis in a 20-year-old female that demonstrates the characteristic clinical, histopathological, and ultramicroscopic features of this disease.

A study on the collagen metabolism and therapy of hepatic fibrosis / 中国药理学通报

Hepatic fibrosis is the hallmark of most chronic liver diseases. Its essense is excessive deposition of extracellular matrix components(ECM) in liver, which occurs due to an imbalance between the production and degradation of matrix. Collagen is the most important part of ECM. Therefore,one important antifibrotic pathway is to effectively inhibit the synthesis of collagen or increase its degradation. The review describes the current progress in collagen metabolism and antifibrotic therapy related to hepatic fibrosis.

Change in the collagen metabolic markers of ischemic cardiomyopathy and its clinical significance / 中国实用内科杂志

Objective To investigate the pathological contribution of serological markers of collagen metabolism including matrix-metalloproteinases(MMPs)and its tissue inhibitors(TIMPs),the markers for type I collagen degradation(ICTP)and synthesis(PICP)to cardiac remodeling of ischemic cardiomyopathy(ICM)as well as the pharmacological regulation effect.Methods Plasma levels of MMP-9,TIMP-1,ICTP and PICP were determined by ELISA and RIA in 86 consecutive ICM patients and 25 age-matched control subjects.Patients were divided into two subgroups according to ACEI-taking or not.Echocardiography were performed in all cases.Results The plasma concentration of MMP-9、TIMP-1 and MMP-9/TIMP-1 was significantly increased in ICM group(all P