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Extracellular matrix (ECM) pathologic remodeling underlies many disorders, including muscular dystrophy. Tissue decellularization removes cellular components while leaving behind ECM components. We generated on-slide decellularized tissue slices from genetically distinct dystrophic mouse models. The ECM of dystrophin- and sarcoglycan-deficient muscles had marked thrombospondin 4 deposition, while dysferlin-deficient muscle had excess decorin. Annexins A2 and A6 were present on all dystrophic decellularized ECMs, but annexin matrix deposition was excessive in dysferlin-deficient muscular dystrophy. Muscle-directed viral expression of annexin A6 resulted in annexin A6 in the ECM. C2C12 myoblasts seeded onto decellularized matrices displayed differential myoblast mobility and fusion. Dystrophin-deficient decellularized matrices inhibited myoblast mobility, while dysferlin-deficient decellularized matrices enhanced myoblast movement and differentiation. Myoblasts treated with recombinant annexin A6 increased mobility and fusion like that seen on dysferlin-deficient decellularized matrix and demonstrated upregulation of ECM and muscle cell differentiation genes. These findings demonstrate specific fibrotic signatures elicit effects on myoblast activity.

Small leucine‐rich proteoglycans, such as decorin and biglycan, play pivotal roles in collagen fibrillogenesis during development, healing, and aging in tendon. Previous work has shown that the absence of decorin and biglycan affects fibril shape and mechanical properties during tendon healing. However, the roles of decorin and biglycan in the healing process of aged tendons are unclear. Therefore the objective of this study was to evaluate the differential roles of decorin and biglycan during healing of patellar tendon injury in aged mice. Aged (300 days old) female Dcn+/+/Bgn+/+ control (WT, n = 52), Dcnflox/flox (I‐Dcn−/−, n = 36), Bgnflox/flox (I‐Bgn−/−, n = 36), and compound Dcnflox/flox/Bgnflox/flox (I‐Dcn−/−/Bgn−/−, n = 36) mice with a tamoxifen‐inducible Cre were utilized. Targeted gene expression, collagen fibril diameter distributions, mechanical properties, and histological assays were employed to assess the effects of knockdown of decorin and/or biglycan at the time of injury. Knockdown resulted in alterations in fibril diameter distribution and scar area, but surprisingly did not lead to many differences in mechanical properties. Biglycan played a larger role in early healing stages, while decorin is more significant in later stages, particularly in scar remodeling. This study highlights some of the differential roles of biglycan and decorin in the regulation of fibril structure and scar area, as well as influencing gene expression during healing in aged mice. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a prevalent malignant tumor of the gastrointestinal system, with the third and second highest incidence and mortality rates globally in 2020, respectively. Immunotherapy has developed rapidly in recent years. Natural killer (NK) cells have received increasing attention in the field of tumor immunotherapy due to their recognition and killing tumor cells without the limitations of major histocompatibility complexes. However, constraints within the tumor microenvironment that impede the infiltration and proliferation of NK cells result in poor efficacy of NK cell therapy for solid tumors. Oncolytic viral therapy is an immunogenic treatment with the potential to enhance anti-tumour immune responses and promote immune cell infiltration. In this study, we synergistically combine NK cells with an oncolytic adenovirus carrying Decorin (rAd.DCN) for the treatment of colorectal cancer (CRC) in a xenograft mouse model. By using Flow cytometry, real-time quantitative PCR and Calcein-AM release assay, we found that rAd.DCN could effectively promote proliferation, activation and degranulation of NK cells, up-regulate expression and secretion of NK cell killing activity-related factors, and enhance their killing activity. The efficacy is better than that of the blank control oncolytic virus rAd.Null. Combined treatment significantly inhibited tumor growth, increased the number of NK cells in peripheral blood, promoted the killing function of NK cells, and increased the expression levels of perforin and IFN-γ. At the same time, more NK cells were recruited to infiltrate tumor tissue. Our study established the feasibility of combination NK cells and oncolytic adenovirus application, thus expanding the scope of potentially curative treatments for NK cells in CRC. [ABSTRACT FROM AUTHOR]

BACKGROUND: Our previous studies found that the polypeptide of Cornus cervi Colla can promote bone growth, which has a good application prospect in the treatment of bone diseases. However, how Cornus cervi Colla works in the body and the principle are not clear. OBJECTIVE: To study the in vivo distribution and tracing of Cornus cervi Colla using fluorescence labeling and tracer technique. METHODS: Cornus cervi Colla was fluorescently labeled using fluorescein isothiocyanate, and the labeling results were detected by fluorescence imaging and UV spectral scanning. Successfully labeled Cornus cervi Colla was injected into mice by gavage, and the absorption of Cornus cervi Colla into blood was detected by laser confocal microscopy, and the distribution of Cornus cervi Colla in mice was detected by small animal in vivo imager. The distribution of Cornus cervi Colla in the mice was detected by laser confocal microscopy. Samples were taken from serum and bone at the time of the strongest fluorescence, and gel electrophoresis was carried out on serum and bone tissue protein solutions, and the components of Cornus cervi Colla absorbed into target organs were determined by secondary mass spectrometry. RESULTS AND CONCLUSION: The fluorescent markers were successfully separated by dextran gel chromatography, and the fluorescence imaging and ultraviolet spectrum scanning proved that the labeling was successful, and the fluorescence substitution degree of FITC-labeled Cornus cervi Colla was 0.953%. The fluorescence intensity of the components of Cornus cervi Colla in the blood showed that Cornus cervi Colla was most distributed in serum after oral administration for 2 hours. The fluorescence images of mice at different times were the same as those of bilateral femur and tibia, indicating that Cornus cervi Colla could play a role by entering the bone. Compared with UniProt database, secondary mass spectrometry showed that the peptide was a characteristic fragment of decorin. It is proved that decorin in Cornus cervi Colla can enter the bone to play a therapeutic role. [ABSTRACT FROM AUTHOR]

Desbuquois dysplasia type 1 (DBQD1) is a recessive chondrodysplasia caused by mutations in the CANT1 gene, encoding for the Golgi Calcium-Activated Nucleotidase 1 (CANT1). The enzyme hydrolyzes UDP, the by-product of glycosyltransferase reactions, but it might play other roles in different cell types. Using a Cant1 knock-out mouse, we demonstrated that CANT1 is crucial for glycosaminoglycan (GAG) synthesis; however, its impact on the biochemical properties of cartilage proteoglycans remains unknown. Thus, in this work, we characterized decorin and aggrecan from primary chondrocyte cultures and cartilage biopsies of mutant mice at post-natal day 4 by Western blots and further investigated their distribution in the cartilage extracellular matrix (ECM) by immunohistochemistry. We demonstrated that the GAG synthesis defect caused by CANT1 impairment led to the synthesis and secretion of proteoglycans with shorter GAG chains compared with wild-type animals. However, this alteration did not result in the synthesis and secretion of decorin and aggrecan in the unglycanated form. Interestingly, the defect was not cartilage-specific since also skin decorin showed a reduced hydrodynamic size. Finally, immunohistochemical studies in epiphyseal sections of mutant mice demonstrated that the proteoglycan structural defect moderately affected decorin distribution in the ECM. [ABSTRACT FROM AUTHOR]

Abstract Mitochondrial dysfunction with oxidative stress contributes to metabolic dysfunction-associated steatotic liver disease (MASLD) progression. We aimed to evaluate the fibrosis predictive efficacy of a novel non-invasive diagnostic panel using metabolic stress biomarkers. From a population-based general cohort, 144 subjects with MASLD were recruited in the development group and underwent magnetic resonance imaging-based liver examinations, anthropometric and laboratory tests. As an external validation group, 41 patients enrolled in a biopsy-evaluated MASLD cohort participated in this study. Liver fat content and stiffness were measured by magnetic resonance (MR) imaging-proton density fat fraction and MR elastography (MRE), respectively. Serologic stress biomarkers were quantitated by ELISA. Multivariate regression showed that waist-to-height ratio, growth differentiation factor-15 (GDF15), γ-glutamyltransferase, decorin, and alkaline-phosphatase were independent predictors of hepatic fibrosis (rank-ordered by Wald). The area under receiver-operator characteristics curve [AUROC (95% CI)) of the metabolic stress index for fibrosis (MSI-F) was 0.912 (0.85‒0.98) and 0.977 (0.92‒1.00) in development and validation groups, respectively. MSI-F also had better diagnostic accuracy (82.6‒92.4%) than other fibrosis indices in the both study cohorts. MSI-F consistently differentiated fibrosis severities across cohorts of MRE-evaluated general population and biopsy-proven patients with MASLD, while other indices showed no or less discrimination. MSI-F, as a novel non-invasive index based on a stress-stimulated protective hormone GDF15 and decorin, effectively predicted hepatic fibrosis. Furthermore, MSI-F may serve as pre-screening tool to increase the population that could be excluded from further evaluation, reducing unnecessary invasive investigations more effectively than other indices.

Abstract Colorectal cancer (CRC) is a prevalent malignant tumor of the gastrointestinal system, with the third and second highest incidence and mortality rates globally in 2020, respectively. Immunotherapy has developed rapidly in recent years. Natural killer (NK) cells have received increasing attention in the field of tumor immunotherapy due to their recognition and killing tumor cells without the limitations of major histocompatibility complexes. However, constraints within the tumor microenvironment that impede the infiltration and proliferation of NK cells result in poor efficacy of NK cell therapy for solid tumors. Oncolytic viral therapy is an immunogenic treatment with the potential to enhance anti-tumour immune responses and promote immune cell infiltration. In this study, we synergistically combine NK cells with an oncolytic adenovirus carrying Decorin (rAd.DCN) for the treatment of colorectal cancer (CRC) in a xenograft mouse model. By using Flow cytometry, real-time quantitative PCR and Calcein-AM release assay, we found that rAd.DCN could effectively promote proliferation, activation and degranulation of NK cells, up-regulate expression and secretion of NK cell killing activity-related factors, and enhance their killing activity. The efficacy is better than that of the blank control oncolytic virus rAd.Null. Combined treatment significantly inhibited tumor growth, increased the number of NK cells in peripheral blood, promoted the killing function of NK cells, and increased the expression levels of perforin and IFN-γ. At the same time, more NK cells were recruited to infiltrate tumor tissue. Our study established the feasibility of combination NK cells and oncolytic adenovirus application, thus expanding the scope of potentially curative treatments for NK cells in CRC.

Introduction: Myokines are produced in response to contractions and mechanical stress caused by exercise and plays a key role in muscle regeneration or control of some diseases. The role of resistance training in the secretion of myokines has been less investigated. The purpose of this study was to investigate the effect of 4 weeks of resistance training on the expression of musclin, apelin and decorin genes in the soleus muscle of male Wistar rats. Methods: The present study was experimental. Sixteen 8-week-old male Wistar rats with an average weight of 223±16.99 grams were randomly divided into 2 groups of control (n=8) and resistance training (n=8). After familiarizing the animals with the laboratory environment and resistance training on the ladder, the rats in the resistance training group trained on the ladder for 4 weeks, 3 days per week. Expression values of musclin, apelin and decorin genes of soleus muscle were measured by RT-PCR method. To analyze the data, independent t test was used at the level of p

Dupuytren's disease (DD) is a prevalent fibroproliferative disorder of the hand, shaped by genetic, epigenetic, and environmental influences. The extracellular matrix (ECM) is a complex assembly of diverse macromolecules. Alterations in the ECM's content, structure and organization can impact both normal physiological functions and pathological conditions. This study explored the content and organization of glycosaminoglycans, proteoglycans, and collagen in the ECM of patients at various stages of DD, assessing their potential as prognostic indicators. This research reveals, for the first time, relevant changes in the complexity of chondroitin/dermatan sulfate structures, specifically an increase of disaccharides containing iduronic acid residues covalently linked to either N-acetylgalactosamine 6-O-sulfated or N-acetylgalactosamine 4-O-sulfated, correlating with the disease's severity. Additionally, we noted an increase in versican expression, a high molecular weight proteoglycan, across stages I to IV, while decorin, a small leucine-rich proteoglycan, significantly diminishes as DD progresses, both confirmed by mRNA analysis and protein detection via confocal microscopy. Coherent anti-Stokes Raman scattering (CARS) microscopy further demonstrated that collagen fibril architecture in DD varies importantly with disease stages. Moreover, the urinary excretion of both hyaluronic and sulfated glycosaminoglycans markedly decreased among DD patients.Our findings indicate that specific proteoglycans with galactosaminoglycan chains and collagen arrangements could serve as biomarkers for DD progression. The reduction in glycosaminoglycan excretion suggests a systemic manifestation of the disease. [ABSTRACT FROM AUTHOR]

The management of hypertrophic scars (HSs), characterized by excessive collagen production, involves various nonsurgical and surgical interventions. However, the absence of a well‐defined molecular mechanism governing hypertrophic scarring has led to less‐than‐ideal results in clinical antifibrotic treatments. Therefore, our study focused on the role of decorin (DCN) and its regulatory role in the TGF‐β/Smad signalling pathway in the development of HSs. In our research, we observed a decrease in DCN expression within hypertrophic scar tissue and its derived cells (HSFc) compared to that in normal tissue. Then, the inhibitory effect of DCN on collagen synthesis was confirmed in Fc and HSFc via the detection of fibrosis markers such as COL‐1 and COL‐3 after the overexpression and knockdown of DCN. Moreover, functional assessments revealed that DCN suppresses the proliferation, migration and invasion of HSFc. We discovered that DCN significantly inhibits the TGF‐β1/Smad3 pathway by suppressing TGF‐β1 expression, as well as the formation and phosphorylation of Smad3. This finding suggested that DCN regulates the synthesis of collagen‐based extracellular matrix and fibrosis through the TGF‐β1/Smad3 pathway. [ABSTRACT FROM AUTHOR]

Aging is a high-risk factor for obstructive and fibrotic lung diseases. Fibrotic lung disease leading to decreased lung function is characterized by interstitial remodeling and tissue scarring (sclerosis), with destruction of alveoli and excess deposition of type I collagen, an extracellular matrix component secreted by fibroblasts. Therefore, regulating transforming growth factor-β (TGF-β) as a profibrotic signal is essential to suppress pulmonary fibrosis. In pulmonary fibrosis, TGF-β signaling is mediated by Smad and YAP/TAZ, and TAZ linked to the pathology of pulmonary function is observed in lung fibroblasts from patients with idiopathic pulmonary fibrosis. Although fibrosis is thought to be irreversible, it is an interventional condition. Decorin (DCN) blocks TGF-β signaling in pulmonary fibrosis, although there are no cellular pharmacological methods to stimulate DCN secretion. We previously showed that chicken eggshell membrane (ESM, a well-known wound-healing material) promotes dcn gene expression in fibroblasts. In this study, we investigated whether ESM stimulates DCN secretion as an endogenous mediator and ameliorates pulmonary fibrosis. Decorin secretion was significantly enhanced in the WI-38 lung fibroblast culture supernatants supplemented with ESM. This effect was increased with major component lysozyme and maximally promoted in experiments with lysozyme and ovotransferrin (the two main proteins in soluble ESM) at a 16:1 concentration ratio, the ratio in the ESM extract. Decorin secretion by ESM modulates TGF-β signaling in lung fibroblasts by reducing TAZ and pSmad2 nuclear localization. Decorin siRNA experiments confirmed that nuclear localization of TAZ is DCN-dependent. In a mouse model of bleomycin-induced pulmonary fibrosis, all fibrotic markers of ESM treatment group such as hydroxyproline (a collagen deposition marker), and both evaluation of fibrosis density by automated thresholding of picrosirius red-stained lung tissue scan images and Ashcroft fibrosis scores, and also the nuclear localization of TAZ were reduced after 2 weeks compared with control group. Furthermore, long-term (22 week) ESM consumption by healthy individuals significantly improved vital capacity and the forced expiratory volume in 1 s to forced vital capacity ratio (FEV1/FVC). This study reveals that ESM, a well-established wound-healing material, may be a potential preventive medicine for pulmonary fibrosis.

Sarcopenia is associated with progressive generalized skeletal muscle weakness, persistent decline in muscle strength, function, and quality of life in the elderly population. The presence of sarcopenia worsens the prognosis of older patients. In this regard, the study of the etiology and pathogenesis of sarcopenia, the identification of early markers for the diagnosis of this disease are relevant areas today. Myokines are secreted by skeletal muscle and play a important role in the regulation of muscle mass and function, metabolic homeostasis. Myokine synthesis disruption may contribute to the development of sarcopenia. In addition, we can see the polymorphism association of various genes with the development of the disease. This review brings together current knowledge about myokines and genetic factors as potential biomarkers for the early diagnosis of sarcopenia.

Radiation-induced heart disease (RIHD), a common side effect of chest irradiation, is a primary cause of mortality among patients surviving thoracic cancer. Thus, the development of novel, clinically applicable cardioprotective agents which can alleviate the harmful effects of irradiation on the heart is of great importance in the field of experimental oncocardiology. Biglycan and decorin are structurally related small leucine-rich proteoglycans which have been reported to exert cardioprotective properties in certain cardiovascular pathologies. Therefore, in the present study we aimed to examine if biglycan or decorin can reduce radiation-induced damage of cardiomyocytes. A single dose of 10 Gray irradiation was applied to induce radiation-induced cell damage in H9c2 cardiomyoblasts, followed by treatment with either biglycan or decorin at various concentrations. Measurement of cell viability revealed that both proteoglycans improved the survival of cardiac cells post-irradiation. The cardiocytoprotective effect of both biglycan and decorin involved the alleviation of radiation-induced proapoptotic mechanisms by retaining the progression of apoptotic membrane blebbing and lowering the number of apoptotic cell nuclei and DNA double-strand breaks. Our findings provide evidence that these natural proteoglycans may exert protection against radiation-induced damage of cardiac cells. [ABSTRACT FROM AUTHOR]

Decorin (DCN), a member of the small leucine-rich proteoglycan gene family, is secreted from stromal fibroblasts with non-cell-autonomous anti-breast-cancer effects. Therefore, in the present study, we sought to elucidate the function of decorin in breast stromal fibroblasts (BSFs). We first showed DCN downregulation in active cancer-associated fibroblasts (CAFs) compared to their adjacent tumor counterpart fibroblasts at both the mRNA and protein levels. Interestingly, breast cancer cells and the recombinant IL-6 protein, both known to activate fibroblasts in vitro, downregulated DCN in BSFs. Moreover, specific DCN knockdown in breast fibroblasts modulated the expression/secretion of several CAF biomarkers and cancer-promoting proteins (α-SMA, FAP- α, SDF-1 and IL-6) and enhanced the invasion/proliferation abilities of these cells through activation of the STAT3/AUF1 signaling. Furthermore, DCN-deficient fibroblasts promoted the epithelial-to-mesenchymal transition and stemness processes in BC cells in a paracrine manner, which increased their resistance to cisplatin. These DCN-deficient fibroblasts also enhanced angiogenesis and orthotopic tumor growth in mice in a paracrine manner. On the other hand, ectopic expression of DCN in CAFs suppressed their active features and their paracrine pro-carcinogenic effects. Together, the present findings indicate that endogenous DCN suppresses the pro-carcinogenic and pro-metastatic effects of breast stromal fibroblasts. [ABSTRACT FROM AUTHOR]

The prevalence of thyroid cancer has shown a progressive rise over time. This study aimed to explore the expression and underlying mechanisms of decorin (DCN) in follicular thyroid carcinoma (FTC), employing bioinformatics analysis and immunohistochemistry techniques. The GSE27155 dataset was obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and core DEGs were identified through data mining and analysis using the R language and online databases. The expression of core DEGs was validated using The Cancer Genome Atlas database. Additionally, the correlation between DCN and clinicopathological stage, tumor-infiltrating lymphocytes, and hotspot molecules in thyroid cancer was assessed using the Gene Expression Profiling Interactive Analysis and TIMER databases. Immunohistochemical (IHC) analysis was then conducted to verify the differential expression of core DCN in FTC and adjacent tissues. We confirmed the downregulation of three DEGs (DCN, GPC3, and PDGFRA). Furthermore, the analysis revealed a significant association between DCN expression and the clinical stage of patients with thyroid cancer (p<0.0001). DCN expression and the infiltration of several immune cells were positively correlated (p<0.01). A significant positive correlation was also noted between DCN and the NRAS and KRAS genes (partial cor>0, p<0.05). Immunohistochemical analyses revealed a significantly lower staining score (3.071 ± 2.493) for DCN protein in cancer tissues than that in adjacent tissues (8.643 ± 2.094) (p<0.0001). DCN is underexpressed and contributes to tumor progression in FTC. Thus, DCN serves as a tumor suppressor gene in FTC and a promising therapeutic target. [ABSTRACT FROM AUTHOR]

Hypertrophic scars (HTS) develop from an excessive synthesis of structural proteins like collagen and a decreased expression of proteoglycans such as decorin. Previous research has demonstrated that decorin expression is significantly down‐regulated in HTS, deep dermal tissue, and thermally injured tissue, reducing its ability to regulate pro‐fibrotic transforming growth factor‐beta 1 (TGF‐β1) and normal fibrillogenesis. However, treatment of HTS fibroblasts with interferon‐alpha 2b (IFN‐α2b) has been shown to reduce excessive collagen synthesis and improve HTS by reducing serum TGF‐β1 levels. The expression of decorin isoforms in HTS is currently unknown and the effects of TGF‐β1 and IFN‐α2b on decorin, decorin isoform expression and type 1 collagen are of great interest to our group. Dermal fibroblasts were treated with TGF‐β1 and/or IFN‐α2b, for 48 h. The expression and secretion of decorin, decorin isoforms and type 1 collagen were quantified with reverse transcription‐quantitative polymerase chain reaction, immunofluorescence staining and enzyme‐linked immunosorbent assays. The mRNA expression of decorin and each isoform was significantly reduced in HTS fibroblasts relative to normal skin. TGF‐β1 decreased the mRNA expression of decorin and decorin isoforms, whereas IFN‐α2b showed the opposite effect. IFN‐α2b significantly inhibited TGF‐β1's effect on the mRNA expression of type I collagen alpha 1 in papillary dermal fibroblasts and overall showed relative effects of inhibiting TGF‐β1. These data support that a further investigation into the structural and functional roles of decorin isoforms in HTS pathogenesis is warranted and that IFN‐α2b is an important agent in reducing fibrotic outcomes. [ABSTRACT FROM AUTHOR]

Background: Myokines may act as protective or causative factors in the pathogenesis of cardiovascular diseases. Conflicting data have been published regarding abnormal levels of myokines in both angina pevtoris and heart failure (HF) patients. Objective: The primary objective of this study was to evaluate the levels of decorin, myonectin, and irisin in individuals diagnosed with angina pectoris and congestive heart failure, and subsequent exposure to each of these conditions. Methods: The present study was conducted at Salah Al-Din Hospital in Tikrit, which took place between 1st from November in 2023 to 30th from January in 2024. The study consisted of a sample of 300 male patients, including 100 diagnosed with congestive heart failure (G1).) and. 100 were diagnosed with angina pectoris (G2). Participants ranged in age from 35 to 55. After a comprehensive medical examination by a qualified physician in this area. After randomization, a control group (C) consisting of 75 healthy men between 35 and 55 years of age was included. Results: When compared to the healthy volunteers (C), the sick groups (G1, G2) showed significantly higher serum concentrations of Decorin, Myonectin, and Irisin (p < 0.01). Regretfully, there was no discernible difference between patients with angina pectoris and those with congestive heart failure. Additionally, this study has provided additional evidence supporting the existence of negative associations between plasma Myonectin levels and Irisin in the same groups. Conclusion: Myokines have been identified as predictive biological markers that exhibit an independent association with an elevated risk of heart failure (HF) and angina pectoris. However, further work is necessary to fully understand their role in predicting unfavourable cardiac remodelling and stratifying clinical outcomes through large-scale clinical studies. Abbreviation: CHF: Congestive Heart Failure; CVD: Cardiovascular Diseases; CAD: coronary artery diseases; DCN: Decorin; CTRP15: Tumor necrosis factor-related protein15. [ABSTRACT FROM AUTHOR]

Interest in studying neonatal development and the improved healing response observed in neonates is increasing, with the goal of using this work to create better therapeutics for tendon injury. Decorin and biglycan are two small leucine-rich proteoglycans that play important roles in collagen fibrillogenesis to develop, maintain, and repair tendon structure. However, little is known about the roles of decorin and biglycan in early neonatal development and healing. The goal of this study was to determine the effects of decorin and biglycan knockdown on Achilles tendon structure and mechanics during neonatal development and recovery of these properties after injury of the neonatal tendon. We hypothesized that knockdown of decorin and biglycan would disrupt the neonatal tendon developmental process and produce tendons with impaired mechanical and structural properties. We found that knockdown of decorin and biglycan in an inducible, compound decorin/biglycan knockdown model, both during development and after injury, in neonatal mice produced tendons with reduced mechanical properties. Additionally, the collagen fibril microstructure resembled an immature tendon with a large population of small diameter fibrils and an absence of larger diameter fibrils. Overall, this study demonstrates the importance of decorin and biglycan in facilitating tendon growth and maturation during neonatal development. [ABSTRACT FROM AUTHOR]

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Objective: This study explores the inhibition of papillary thyroid carcinoma proliferation by Decorin via the EGFR/SHP2/FER pathway. Method: ology: Thirty-two pairs of papillary thyroid carcinoma tissues and adjacent normal tissues were collected for immunohistochemical analysis. Thyroid cancer cell lines with overexpressed or silenced Decorin were employed in subcutaneous tumor formation experiments in nude mice. Cell membrane proteins were extracted for Western blot and immunofluorescence analyses. Results: Reduced Decorin expression in human papillary thyroid carcinoma was associated with inhibited formation of the EGFR/SHP2/FER complex. Immunohistochemical analysis revealed lower Decorin levels in carcinoma tissues compared to adjacent normal tissues, corroborated by decreased Decorin and PTEN levels in carcinoma as shown by Western Blot. Overexpression of Decorin in mouse models diminished tumor growth, an effect reversed by Decorin silencing and mitigated by FER inhibition. Decorin modulated Rab5-GTP and Rab7-GTP levels, impacting endosome transition and subsequent signaling pathways. Conclusion: Decorin inhibits papillary thyroid carcinoma proliferation by disrupting the EGFR/SHP2/FER pathway and modulating endosomal transport.

Glioblastoma (GBM) accounts for approximately half of all malignant brain tumors, and it remains lethal with a five-year survival of less than 10%. Despite the immense advancements in the field, it has managed to evade even the most promising therapeutics: immunotherapies. The main reason is the highly spatiotemporally heterogeneous and immunosuppressive GBM tumor microenvironment (TME). Accounting for this complex interplay of TME-driven immunosuppression is key to developing effective therapeutics. This review will explore the immunomodulatory role of the extracellular matrix (ECM) by establishing its contribution to the TME as a key mediator of immune responses in GBM. This relationship will help us elucidate therapeutic targets that can be leveraged to develop and deliver more effective immunotherapies. [ABSTRACT FROM AUTHOR]

Objective: This study analyzes the levels of peripheral blood placental growth factor (PLGF), body mass index (BMI), decorin (DCN), lactate dehydrogenase (LDH), uric acid (UA), and clinical indicators of patients with preeclampsia (PE), and establishes a predictive risk model of PE, which can provide a reference for early and effective prediction of PE. Methods: 81 cases of pregnant women with PE who had regular prenatal checkups and delivered in Jinshan Branch of Shanghai Sixth People's Hospital from June 2020 to December 2022 were analyzed, and 92 pregnant women with normal pregnancies who had their antenatal checkups and delivered at the hospital during the same period were selected as the control group. Clinical data and peripheral blood levels of PLGF, DCN, LDH, and UA were recorded, and the two groups were subjected to univariate screening and multifactorial logistic regression analysis. Based on the screening results, the diagnostic efficacy of PE was evaluated using the receiver operating characteristic (ROC) curve. Risk prediction nomogram model was constructed using R language. The Bootstrap method (self-sampling method) was used to validate and produce calibration plots; the decision curve analysis (DCA) was used to assess the clinical benefit rate of the model. Results: There were statistically significant differences in age, pre-pregnancy BMI, gestational weight gain, history of PE or family history, family history of hypertension, gestational diabetes mellitus, and history of renal disease between the two groups (P < 0.05). The results of multifactorial binary logistic stepwise regression revealed that peripheral blood levels of PLGF, DCN, LDH, UA, and prepregnancy BMI were independent influences on the occurrence of PE (P < 0.05). The area under the curve of PLGF, DCN, LDH, UA levels and pre-pregnancy BMI in the detection of PE was 0.952, with a sensitivity of 0.901 and a specificity of 0.913, which is better than a single clinical diagnostic indicator. The results of multifactor analysis were constructed as a nomogram model, and the mean absolute error of the calibration curve of the modeling set was 0.023, suggesting that the predictive probability of the model was generally compatible with the actual value. DCA showed the predictive model had a high net benefit in the range of 5% to 85%, suggesting that the model has clinical utility value. Conclusion: The occurrence of PE is related to the peripheral blood levels of PLGF, DCN, LDH, UA and pre-pregnancy BMI, and the combination of these indexes has a better clinical diagnostic value than a single index. The nomogram model constructed by using the above indicators can be used for the prediction of PE and has high predictive efficacy. [ABSTRACT FROM AUTHOR]

Proteoglycans are differentially expressed in different atherosclerotic plaque phenotypes, with biglycan and decorin characteristic of ruptured plaques and versican and hyaluronan more prominent in eroded plaques. Following plaque disruption, the exposure of extracellular matrix (ECM) proteins triggers platelet adhesion and thrombus formation. In this study, the impact of differential plaque composition on platelet function and thrombus formation was investigated. Platelet adhesion, activation and thrombus formation under different shear stress conditions were assessed in response to individual proteoglycans and composites representing different plaque phenotypes. The results demonstrated that all the proteoglycans tested mediated platelet adhesion but not platelet activation, and the extent of adhesion observed was significantly lower than that observed with type I and type III collagens. Thrombus formation upon the rupture and erosion ECM composites was significantly reduced (p < 0.05) compared to relevant collagen alone, indicating that proteoglycans negatively regulate platelet collagen responses. This was supported by results demonstrating that the addition of soluble biglycan or decorin to whole blood markedly reduced thrombus formation on type I collagen (p < 0.05). Interestingly, thrombus formation upon the erosion composite displayed aspirin sensitivity, whereas the rupture composite was intensive to aspirin, having implications for current antiplatelet therapy regimes. In conclusion, differential platelet responses and antiplatelet efficacy are observed on ECM composites phenotypic of plaque rupture and erosion. Proteoglycans inhibit thrombus formation and may offer a novel plaque-specific approach to limit arterial thrombosis. [ABSTRACT FROM AUTHOR]

to investigate the serum levels of decorin, a small leucine-rich proteoglycan, in women diagnosed with polycystic ovary syndrome (PCOS) and concurrently presenting with moderate to severe acne vulgaris. PATIENTS AND METHODS: Sixty patients with acne vulgaris symptoms, subsequently diagnosed with PCOS according to the revised Rotterdam criteria, were enrolled in the study. Acne severity was assessed using the acne global severity scale (AGSS), with patients fitting AGSS category 4 (moderate) and 5 (severe) grouped into two separate cohorts of 30 individuals each. The moderate acne group comprised patients with few inflammatory lesions and a minor nodule alongside predominantly non-inflammatory lesions, whereas the severe group contained patients with multiple nodules and a mix of non-inflammatory and inflammatory lesions. A control group of twenty healthy women without acne vulgaris or PCOS was also established. The study measured serum testosterone, follicle- stimulating hormone (FSH), Luteinizing Hormone (LH), and insulin levels, and calculated insulin resistance via the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) formula. Quantitative sandwich enzyme immunoassay was employed to determine decorin levels from venous blood samples. RESULTS: While age, body mass index (BMI), serum FSH, LH, testosterone, and HOMA-IR values demonstrated similarity between the moderate and severe acne cohorts, comparisons between the control and both acne groups (AGSS-4 and AGSS-5) revealed significantly elevated values in the latter, excluding age, BMI, and FSH. Importantly, the serum decorin levels in both acne groups were substantially higher than in controls. A significant positive correlation was observed between serum decorin levels and both HOMA-IR (r=7.88, p<0.01) and testosterone (r=0.813, p<0.01). CONCLUSIONS: This study suggests that elevated circulating decorin levels play a pivotal role in the manifestation of acne vulgaris in women with PCOS. [ABSTRACT FROM AUTHOR]

• Quantification of tissue glycosaminoglycans via mass spectrometry provides unique insight into extracellular matrix remodeling after TBI. • Decreases in N-sulfated heparan sulfate, 4S and 2S/4S chondroitin sulfate, and increases in 0S chondroitin sulfate were observed 24 h after injury, which normalized 7d after injury. • Increases in total heparan sulfate, chondroitin sulfate, and hyaluronan were observed at the site of injury after 7d. • Unbiased transcriptomics analyses revealed upregulation of the proteoglycans glypican-3 and decorin, and the biosynthesis enzyme hyaluronan synthase 2 at 7d post-injury. These transcriptional changes may be responsible for observed increases in glycosaminoglycans. • Behavioral assessment of Dcn−/− mice 7d post-injury suggests a protective role for decorin upregulation following TBI. Traumatic brain injury (TBI) is the leading cause of death and disability due to injury worldwide. Extracellular matrix (ECM) remodeling is known to significantly contribute to TBI pathophysiology. Glycosaminoglycans, which are long-chain, variably sulfated polysaccharides abundant within the ECM, have previously been shown to be substantially altered after TBI. In this study, we sought to delineate the dynamics of glycosaminoglycan alterations after TBI and discover the precise biologic processes responsible for observed glycosaminoglycan changes after injury. We performed state-of-the art mass spectrometry on brain tissues isolated from mice after TBI or craniotomy-alone. We observed dynamic changes in glycosaminoglycans at Day 1 and 7 post-TBI, with heparan sulfate, chondroitin sulfate, and hyaluronan remaining significantly increased after a week vis-à-vis craniotomy-alone tissues. We did not observe appreciable changes in circulating glycosaminoglycans in mice after experimental TBI compared to craniotomy-alone nor in patients with TBI and severe polytrauma compared to control patients with mild injuries, suggesting increases in injury site glycosaminoglycans are driven by local synthesis. We subsequently performed an unbiased whole genome transcriptomics analysis on mouse brain tissues 7 days post-TBI and discovered a significant induction of hyaluronan synthase 2, glypican-3, and decorin. The functional role of decorin after injury was further examined through multimodal behavioral testing comparing wild-type and Dcn −/− mice. We discovered that genetic ablation of Dcn led to an overall negative effect of TBI on function, exacerbating motor impairments after TBI. Collectively, our results provide a spatiotemporal characterization of post-TBI glycosaminoglycan alterations in the brain ECM and support an important adaptive role for decorin upregulation after TBI. [ABSTRACT FROM AUTHOR]

Considering the therapeutic efficacy of Stachydrine on breast cancer (BC), this study aims to decipher the relevant mechanism. The effects of Stachydrine on BC cell viability, proliferation and apoptosis were firstly investigated. Then, Bioinformatics was applied to sort out the candidate interacting with Stachydrine as well as its expression and downstream target in BC. Relative expressions of genes of interest as well as proliferation‐ and apoptosis‐related factors in BC cells were quantified through quantitative reverse‐transcription PCR and western blot as appropriate. As a result, Stachydrine inhibited the proliferation, down‐regulated the expressions of proliferating cell nuclear antigen and CyclinD1, enhanced cell cycle arrest and apoptosis, and up‐regulated the levels of Cleaved caspase‐3 and Cleaved caspase‐9 in BC cells. Phospholipase A2 Group IIA (PLA2G2A) was predicted as the candidate interacting with Stachydrine and to be lowly expressed in BC. PLA2G2A silencing reversed while PLA2G2A overexpression reinforced the effects of Stachydrine. Decorin (DCN) was the downstream target of PLA2G2A and also lowly expressed in BC. PLA2G2A silencing counteracted yet overexpressed PLA2G2A strengthened the promoting effects of Stachydrine on DCN level. Collectively, Stachydrine inhibits the growth of BC cells to promote cell cycle arrest and apoptosis via PLA2G2A/DCN axis. [ABSTRACT FROM AUTHOR]

Despite Non-small cell lung cancer (NSCLC) ranks among the most deadly cancers worldwide, and currently, apart from a low percentage, targetable molecules have not been identified in its etiopathogenesis. The relationship between the proteoglycans decorin and biglycan, which are present in the extracellular matrix of cells, and transforming growth factor Beta-1 (TGF-B1), has been shown in many cancers. We investigated the significance of these molecules in NSCLC. Fasting serum levels of decorin, biglycan, and TGF-B1 were obtained from 48 newly diagnosed NSCLC patients and compared with those of 48 adult control subjects matched for age and demographics. Demographic data, baseline laboratory values, and ELISA results were compared between the groups. The median age was 65(39–83) similar in both groups. There was no relation between demographic and clinical parameters and the levels of decorin, biglycan, and TGF-B1 in the NSCLC group. However, in comparison to the control group, NSCLC patients had significantly higher levels of biglycan (42.55 ± 27.40 vs. 24.38 ± 12.05 ng/mL, p= 0.026) and TGF-B1 (15.55 ± 9.16 vs. 10.07 ± 7.8 pg/mL, p= 0.001), while decorin levels were significantly lower (6.64 ± 1.92 vs. 10.28 ± 3.13 ng/mL, p= 0.002). In the multivariate regression analysis; Decorin < 8.13 ng/mL (OR, 10.96; 95% CI: 3.440–34.958), current smoking (OR, 3.81; 95% CI: 1.320–10.998), COPD (OR, 43.6; 95% CI: 2.082–913.081), and lower BMI (OR, 1.22; 95% CI: 1.070–1.405, p= 0.003) were identified as independent predictive markers for NSCLC diagnosis. The decreased serum decorin level is an independent marker for NSCLC. Further studies are needed to investigate the prognostic significance of decorin on survival and its potential as a target in treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Fucoxanthin (Fx) is a representative marine carotenoid. To achieve clinical application of Fx toward cancer treatment, it is important to clarify the presence or absence of its effect in patient-derived xenograft (PDX) mice. Here, we investigated the anticancer effects of Fx in pancreatic cancer (PC)-PDX mice. Consequently, our results suggest that the increase in decorin (DCN) and pro-oxidant p-p38(Thr180/Tyr182) and phospho c-Jun N-terminal kinase (pJNK)(Thr183/Tyr185)-related signals and the inhibition of insulin growth factor binding protein 2 (IGFBP2)-, epithelial cell adhesion molecule (EpCAM)-, and lipocalin 2 (LCN2)-related signals are key regulators of tumor suppression in the PC-PDX mice. The protein alterations in the mice were partially supported by in vitro experiments. Therefore, Fx may be a promising candidate for cancer therapy in patients with PC. Pancreatic cancer (PC) is one of the most fatal cancers, and there is an urgent need to develop new anticancer agents with fewer side effects for the treatment of this condition. A patient-derived xenograft (PDX) mouse model transplanted with cancer tissue from patients is widely accepted as the best preclinical model for evaluating the anticancer potential of drug candidates. Fucoxanthin (Fx) is a highly polar carotenoid contained in edible marine brown algae and possesses anticancer activity. However, there is a lack of data on the effects of Fx in PDX models. We investigated the anticancer effects of Fx in PDX mice transplanted with cancer tissues derived from a patient with PC (PC-PDX) using comprehensive protein expression assay. Fx administration (0.3%Fx diet) ad libitum for 27 days significantly abrogated tumor development (0.4-fold) and induced tumor differentiation in PC-PDX mice, as compared to those in the control mice. Fx significantly upregulated the expression of non-glycanated DCN (2.4-fold), tended to increase the expressions of p-p38(Thr180/Tyr182) (1.6-fold) and pJNK(Thr183/Tyr185) (1.8-fold), significantly downregulated IGFBP2 (0.6-fold) and EpCAM (0.7-fold), and tended to decrease LCN2 (0.6-fold) levels in the tumors of the PC-PDX mice, as compared to those in the control mice. Some of the protein expression patterns were consistent with the in vitro experiments. That is, treatment of fucoxanthinol (FxOH), a prime metabolite derived from dietary Fx, enhanced non-glycanated DCN, p-p38(Thr180/Tyr182), and pJNK(Thr183/Tyr185) levels in human PC PANC-1 and BxPC-3 cells.These results suggested that Fx exerts anticancer and differentiation effects in a PC-PDX mice through alterations of some multifunctional molecules. [ABSTRACT FROM AUTHOR]

• Preeclamptic women with acute renal failure had significantly higher Syndecan-1 and Heparin Sulphate levels. • Among those with other outcomes (pulmonary edema, Eclampsia, and HELLP syndrome), endo -glycocalyx disruption markers were insignificantly higher than those without any adverse outcomes. • Assessing the Levels of biomarkers, especially the glycocalyx degradation products may have a role, in combination with other biomarkers and clinical parameters, in identifying the risk of developing adverse maternal outcomes in severe pre-eclampsia. Identifying preeclamptic women with an increased risk of severe maternal complications can aid in timely interventions to optimize pregnancy outcomes. Newer biomarkers such as Decorin and markers of endo glycocalyx disruption were assessed in earlier studies for its role in predicting preeclampsia, but their role in identifying those with adverse maternal outcomes is limited. This study aimed to evaluate the association of these biomarkers with adverse maternal outcomes in women with severe pre-eclampsia. Markers of glycocalyx disruption may be further explored for their role along with clinical features and other biomarkers in identifying women at higher risk of maternal complications. [ABSTRACT FROM AUTHOR]

Background and aims: Fatty diet can affect the expression of myokines. Thus, the aim of this study was to evaluate the effect of aerobic and resistance training secreted protein acidic rich in cysteine (SPARC), decorin (DCN), and myonectin muscle gene expression in rats fed with a high-fat diet. Methods: In this experimental study, 32 rats were randomly divided into healthy control, obese control, obese+aerobic exercise, and obese+resistance exercise groups. The training program was implemented for 4 weeks at aerobic moderate intensity (50% VO2max in the first week and 65% VO2max in the last week). For resistance training, the animals were also trained to climb the ladder (height 110 cm, slope 80%, and the distance between the bars of the ladder 2 cm), which is based on the determination of one-repetition maximum (1RM). Obese rats received a dose of 0.5 mL/100 g of body weight orally by gavage for 4 weeks and 5 days a week. Results: There was no significant difference between the groups in terms of DCN expressions (P=0.702). However, the expression of SPARC (P=0.039) and myonectin in the obese control group was significantly increased compared to the healthy control (P=0.038). The expression of SPARC and myonectin in the aerobic training group (P=0.038, P=0.042) and the resistance training group (P=0.048, P=0.049) was significantly decreased in comparison to obesity control. Resistance training caused a greater decrease in myonectin compared to aerobic training (P=0.049). Conclusion: The findings revealed that aerobic and resistance exercises are effective in reducing SPARC and myonectin expression in the skeletal muscle of rats fed with a high-fat diet.

Pancreatic cancer (PC) is one of the most fatal cancers, and there is an urgent need to develop new anticancer agents with fewer side effects for the treatment of this condition. A patient-derived xenograft (PDX) mouse model transplanted with cancer tissue from patients is widely accepted as the best preclinical model for evaluating the anticancer potential of drug candidates. Fucoxanthin (Fx) is a highly polar carotenoid contained in edible marine brown algae and possesses anticancer activity. However, there is a lack of data on the effects of Fx in PDX models. We investigated the anticancer effects of Fx in PDX mice transplanted with cancer tissues derived from a patient with PC (PC-PDX) using comprehensive protein expression assay. Fx administration (0.3%Fx diet) ad libitum for 27 days significantly abrogated tumor development (0.4-fold) and induced tumor differentiation in PC-PDX mice, as compared to those in the control mice. Fx significantly upregulated the expression of non-glycanated DCN (2.4-fold), tended to increase the expressions of p-p38(Thr180/Tyr182) (1.6-fold) and pJNK(Thr183/Tyr185) (1.8-fold), significantly downregulated IGFBP2 (0.6-fold) and EpCAM (0.7-fold), and tended to decrease LCN2 (0.6-fold) levels in the tumors of the PC-PDX mice, as compared to those in the control mice. Some of the protein expression patterns were consistent with the in vitro experiments. That is, treatment of fucoxanthinol (FxOH), a prime metabolite derived from dietary Fx, enhanced non-glycanated DCN, p-p38(Thr180/Tyr182), and pJNK(Thr183/Tyr185) levels in human PC PANC-1 and BxPC-3 cells.These results suggested that Fx exerts anticancer and differentiation effects in a PC-PDX mice through alterations of some multifunctional molecules.

Desbuquois dysplasia type 1 (DBQD1) is a recessive chondrodysplasia caused by mutations in the CANT1 gene, encoding for the Golgi Calcium-Activated Nucleotidase 1 (CANT1). The enzyme hydrolyzes UDP, the by-product of glycosyltransferase reactions, but it might play other roles in different cell types. Using a Cant1 knock-out mouse, we demonstrated that CANT1 is crucial for glycosaminoglycan (GAG) synthesis; however, its impact on the biochemical properties of cartilage proteoglycans remains unknown. Thus, in this work, we characterized decorin and aggrecan from primary chondrocyte cultures and cartilage biopsies of mutant mice at post-natal day 4 by Western blots and further investigated their distribution in the cartilage extracellular matrix (ECM) by immunohistochemistry. We demonstrated that the GAG synthesis defect caused by CANT1 impairment led to the synthesis and secretion of proteoglycans with shorter GAG chains compared with wild-type animals. However, this alteration did not result in the synthesis and secretion of decorin and aggrecan in the unglycanated form. Interestingly, the defect was not cartilage-specific since also skin decorin showed a reduced hydrodynamic size. Finally, immunohistochemical studies in epiphyseal sections of mutant mice demonstrated that the proteoglycan structural defect moderately affected decorin distribution in the ECM.

Abstract Background Higher circulating levels of trimethylamine N-oxide (TMAO), which is a metabolite that can be produced by the gut microbiota from L-carnitine (LC), have been associated with bone mineral density (BMD). Because LC supplementation can improve bone density and microstructural properties in animal models, this study aimed to examine the effects of 12 weeks of LC supplementation on BMD and selected blood markers involved in bone metabolism of postmenopausal women participating in a resistance training (RT) program. Methods Twenty-seven postmenopausal women, who had not been treated for osteoporosis, with a total T-score above − 3.0 and no diet differences completed 12 weeks of RT. The participants’ diets were supplemented with either 1 g of LC-L-tartrate and 3 g of leucine per day (LC group) or 4 g of leucine per day as a placebo (PLA group), in a double-blind fashion. Results After the intervention in the LC group, plasma total carnitine and serum decorin levels were higher than the corresponding preintervention values (p = 0.040 and p = 0.042, respectively). Moreover, plasma TMAO and serum SPARC levels were higher in the LC group than the corresponding postintervention values in the PLA group (p

Background: Skeletal muscle is a tissue that secretes myokines from muscle cells in response to training stimuli and muscle contractions. Therefore, this study aimed to investigate the effect of 4-week moderate-intensity aerobic exercise on the expression of three genes: apelin, decorin, and musclin in the skeletal muscle fibers of Wistar rats. In addition, the study examined the changes in gene expression levels during the training period. Methods: The present study enrolled 16 male Wistar rats with an approximate age of eight weeks and a weight range of 200-220 grams. They were randomly divided into two equal groups: An aerobic exercise group (n=8) and a control group (n=8). During the four-week training period, the experimental group performed aerobic exercises on a treadmill with an intensity of 50-70% of their maximum power, for three sessions per week, while the control group did not engage in any activity. After completing the training period, the rats were sacrificed 48 hours later to evaluate the gene expression of the study variables using the real-time PCR method for tissue analysis. An independent t-test was used to examine the difference between groups, and statistical significance was set at P

Abstract Background The interplay between gut microbiota and tumor microenvironment (TME) in the pathogenesis of colorectal cancer (CRC) is largely unknown. Here, we elucidated the functional role of B. adolescentis and its possible mechanism on the manipulation of Decorin+ macrophages in colorectal cancer. Methods The relative abundance of B. adolescentis in tumor or para-tumor tissue of CRC patients was analyzed. The role of B. adolescentis was explored in the CRC animal models. The single cell-RNA sequencing (scRNA-seq) was used to investigate the myeloid cells subsets in TME. The expression level of TLR2/YAP axis and its downstream Decorin in macrophages were tested by Western blot and qRT-PCR. Knockdown of Decorin in Raw264.7 was performed to investigate the effect of Decorin+ macrophages on subcutaneous tumor formation. Multi-immunofluorescence assay examined the number of Decorin+ macrophages on the CRC tissue. Results We found that the abundance of B. adolescentis was significantly reduced in tumor tissue of CRC patients. Supplementation with B. adolescentis suppressed AOM/DSS-induced tumorigenesis in mice. ScRNA-seq and animal experiment revealed that B. adolescentis increased Decorin+ macrophages. Mechanically, Decorin was activated by TLR2/YAP axis in macrophages. The abundance of B. adolescentis was correlated with the number of Decorin+ macrophages and the expression level of TLR2 in tumor tissue of CRC patients. Conclusions These results highlight that B. adolescentis induced Decorin+ macrophages and provide a novel therapeutic target for probiotic-based modulation of immune microenvironment in CRC.

AbstractBackground Benign breast lesions are often associated with hard nodule formation after microwave ablation (MWA), which persists for a long time and causes problems in patients. The aim of this study was to evaluate the efficacy of decorin in the treatment of hard nodule formation and its potential mechanism of action.Methods Using a Bama miniature pig model of mammary gland hyperplasia, immunohistochemistry, Masson’s trichrome and western blotting were firstly applied to compare the extent of fibrosis and activation of key members of the TGF-β1/SMAD and MAPK signaling pathways of hard nodule in the control and MWA groups, and then the extent of fibrosis and expression of signaling pathways in hard nodule were examined after application of decorin.Results The results showed that the MWA group had increased levels of TGF-β1, p-SMAD2/3, p-ERK1/2, and collagen I proteins and increased fibrosis at 2 weeks, 4 weeks, and 3 months after MWA. After decorin treatment, the expression levels of each protein were significantly downregulated, and the degree of fibrosis was reduced at 2 weeks, 4 weeks, and 3 months after MWA compared with the MWA group.Conclusion In conclusion, these results suggest that activation of TGF-β1 may play an important role in hard nodule formation and that decorin may reduce hard nodule formation after MWA in a model of mammary gland hyperplasia by inhibiting the TGF-β1/SMAD and MAPK signaling pathways.

Background: There is still a profound lack of efficient therapeutic strategies against pancreatic and other periampullary adenocarcinoma. Surgery is seldom possible, leaving palliative chemotherapy the only option for most patients. Chemotherapy treatment is however often accompanied by serious side-effects, and the identification of biomarkers for early prediction of disease and treatment-associated symptoms could help alleviate patient suffering. This study investigated the dynamic interrelationship between immune-related serum proteins, routine biomarkers, and health-related quality of life (HRQoL) factors during chemotherapy treatment of patients enrolled in the prospective, observational study Chemotherapy, Host response And Molecular dynamics in Periampullary cancer (CHAMP). Methods: Proximity extension assay was applied to analyse 92 immune-associated proteins in longitudinal serum samples from 75 patients, 18 treated with curative and 57 with palliative intent. HRQoL data were available from all patients at baseline (BL), from 41 patients at three months, and from 23 patients at six months. Information on routine laboratory parameters albumin, CA19-9, CEA and CRP were collected from medical charts. Results: In total nine proteins; chemokine (C–C motif) ligand 23 (CCL23), cluster of differentiation 4 (CD4), cluster of differentiation 28 (CD28), decorin (DCN), galectin-1 (Gal-1), granzyme B (GZMB), granzyme H (GZMH), matrix metallopeptidase 7 (MMP7), and monocyte chemotactic protein-1 (MCP-1) were strongly correlated (Spearman's Rho ≤ -0.6 or ≥ 0.6) with either cognitive functioning (DCN), emotional functioning (DCN, MCP-1), dyspnoea (CD28, GZMB, GZMH) or insomnia (CCL23, CD4, Gal-1, MMP7) during treatment. Associations between routine laboratory parameters (CA 19–9, CA-125, CRP, CEA and albumin) and HRQoL factors were overall weaker. None of the investigated proteins were associated with pain. Conclusions: This is, to our knowledge, the first study exploring associations between serum biomarkers and HRQoL in patients with pancreatic or other periampullary cancer, and some findings merit further validation. The associations of DCN and MCP-1with impaired cognitive and/or emotional functioning are of particular interest, given their established link to various neurodegenerative conditions. Chemotherapy is known to cause persistent cognitive dysfunction with effects on memory and executive function, referred to as "chemo brain". It would therefore be of great value to identify biomarkers for early detection and management of this debilitating condition. Trial registration: Clinical Trial Registration: NCT03724994. [ABSTRACT FROM AUTHOR]

Thin endometrium, defined as an endometrial thickness of less than 7 mm during the late follicular phase, is a common cause of frequent cancelation of embryo transfers or recurrent implantation failure during assisted reproductive treatment. Small proteoglycans regulate intracellular signaling cascades by bridging other matrix molecules and tissue elements, affecting cell proliferation, adhesion, migration, and cytokine concentration. The aim of the study is to investigate the role of small leucine-rich proteoglycans in the pathogenesis of thin and thick human endometrium and their differences from normal endometrium in terms of fine structure properties. Normal, thin, and thick endometrial samples were collected, and small leucine-rich proteoglycans (SLRPs), decorin, lumican, biglycan, and fibromodulin immunoreactivities were comparatively analyzed immunohistochemically. The data were compared statistically. Moreover, ultrastructural differences among the groups were evaluated by transmission electron microscopy. The immunoreactivities of decorin, lumican, and biglycan were higher in the thin endometrial glandular epithelium and stroma compared to the normal and thick endometrium (p < .001). Fibromodulin immunoreactivity was also higher in the thin endometrial glandular epithelium than in the normal and thick endometrium (p < .001). However, there was no statistical difference in the stroma among the groups. Ultrastructural features were not profoundly different among cases. Telocytes, however, were not seen in the thin endometrium in contrast to normal and thin endometrial tissues. These findings suggest a possible role of changes in proteoglycan levels in the pathogenesis of thin endometrium. [ABSTRACT FROM AUTHOR]

Objective • This study aims to investigate the role of decorin in the adhesion process of Treponema pallidum subspecies pallidum (T. pallidum) to human brain microvascular endothelial cells. Methods • The study involved an in vitro experimental design. Western blot analysis was conducted to determine the protein expression level of decorin in the cells. The cells were divided into four groups: Tp group, inactivated Tp group, LPS group, and negative control group. The adhesion of T. pallidum to the cells was analyzed using darkfield microscopy counting and quantitative polymerase chain reaction (qPCR). The cells were divided into four groups based on different preprocessing treatments: control group, decorin group, DCN-siRNA group, and DCN-siRNA+decorin group. Changes in the F-actin of the cells were explored using confocal laser scanning microscopy. The cells were divided into the Tp group, Tp+decorin group, and control group. Results • Western blot analysis showed high expression of decorin in the Tp group and LPS group. Darkfield microscopy counting revealed a significantly higher number of T. pallidum adhered to a single cell in the decorin group compared to the control group. Conversely, the number of adhered T. pallidum was significantly lower in the DCN-siRNA group compared to the control group. qPCR results indicated a considerably higher T. pallidum load in the decorin group compared to the control group. In the Tp group, T. pallidum treatment induced the reorganization of F-actin, while the distribution of F-actin in the Tp+decorin group was comparable to that of the control group. Conclusions • Decorin enhances the adhesion of T. pallidum to human brain microvascular endothelial cells, suggesting that decorin may act as one of the receptors regulating the adhesion of T. pallidum to cells. Furthermore, T. pallidum treatment triggers the rearrangement of F-actin in cells, and decorin plays a protective role in this process. [ABSTRACT FROM AUTHOR]

Background and aims: Fatty diet can affect the expression of myokines. Thus, the aim of this study was to evaluate the effect of aerobic and resistance training secreted protein acidic rich in cysteine (SPARC), decorin (DCN), and myonectin muscle gene expression in rats fed with a high-fat diet. Methods: In this experimental study, 32 rats were randomly divided into healthy control, obese control, obese+aerobic exercise, and obese+resistance exercise groups. The training program was implemented for 4 weeks at aerobic moderate intensity (50% VO2max in the first week and 65% VO2max in the last week). For resistance training, the animals were also trained to climb the ladder (height 110 cm, slope 80%, and the distance between the bars of the ladder 2 cm), which is based on the determination of one-repetition maximum (1RM). Obese rats received a dose of 0.5 mL/100 g of body weight orally by gavage for 4 weeks and 5 days a week. Results: There was no significant difference between the groups in terms of DCN expressions (P=0.702). However, the expression of SPARC (P=0.039) and myonectin in the obese control group was significantly increased compared to the healthy control (P=0.038). The expression of SPARC and myonectin in the aerobic training group (P=0.038, P=0.042) and the resistance training group (P=0.048, P=0.049) was significantly decreased in comparison to obesity control. Resistance training caused a greater decrease in myonectin compared to aerobic training (P=0.049). Conclusion: The findings revealed that aerobic and resistance exercises are effective in reducing SPARC and myonectin expression in the skeletal muscle of rats fed with a high-fat diet. [ABSTRACT FROM AUTHOR]

Despite the discovery of numerous driving and passenger genes that play key roles in cancer characteristics, progress in cancer treatment has not been satisfactory. This is mainly because conventional therapies are neither selective nor targeted. Another important reason is that cancer cells rapidly develop resistance to chemotherapeutic agents due to excessive accumulation of mutations and/or epigenetic changes. In light of this, we believe that the discovery of new targets and key genes/proteins could improve treatment options. In this study, tissue samples (tumor and normal mucosa) were first collected from the colon or rectum by right or left hemicolectomy. Proteomic analysis was then performed using the label-free nLC-MS/MS method. We determined 77 proteins with statistically significant differences in expression levels between cancerous and normal mucosa. While the expression of 76 proteins was decreased in cancer tissues, only one protein (RNA-binding motif protein_X chromosome—RBMX) was increased in colorectal cancer tissues. The bioinformatics portal Metascape was used to determine the biological processes involved. 77 proteins with significantly different expression between cancerous and normal tissues were compared with the UALCAN platform using data from the Clinical Proteomics Tumor Analysis Consortium (CPTAC). The results for 45 of the 77 proteins clearly matched the CPTAC dataset. Western blot studies confirmed that RBMX protein (critical for gene transcription and alternative splicing of various pre-mRNAs) was increased 2.04-fold, while decorin protein (a matrix proteoglycan with tumor suppressor functions) was dramatically decreased by about 6.04-fold in tumor samples compared with normal mucosa. [ABSTRACT FROM AUTHOR]

To investigate the possible degradation of the intramuscular connective tissue (IMCT) with cathepsin L, isolated IMCTs were incubated with purified cathepsin L in vitro. Here, we prepared purified cathepsin L from bovine pancreas by using DEAE Sephacel, Sephacryl S-100 HR, SP Sepharose FF, and con A-Sepharose affinity chromatography in sequence. An SDS-PAGE analysis of CNBr-digested peptides showed that the degradation of collagen in IMCT could take place on terminal non-helical peptides rather than the triple helix region. Decorin (DCN) was clearly degraded at a pH of 5.0. The TP and TO of intramuscular connective tissue decreased to 41.41 °C and 43.79 °C, respectively. In the cathepsin L treatment of pH 5.0, the decreases in the TP and TO of IMCT were more sensitive than they were at pH 5.5~6.5. [ABSTRACT FROM AUTHOR]

Bone biomineralization is a complex process in which type I collagen and associated non-collagenous proteins (NCPs), including glycoproteins and proteoglycans, interact closely with inorganic calcium and phosphate ions to control the precipitation of nanosized, non-stoichiometric hydroxyapatite (HAP, idealized stoichiometry Ca10(PO4)6(OH)2) within the organic matrix of a tissue. The ability of certain vertebrate tissues to mineralize is critically related to several aspects of their function. The goal of this study was to identify specific NCPs in mineralizing and non-mineralizing tissues of two animal models, rat and turkey, and to determine whether some NCPs are unique to each type of tissue. The tissues investigated were rat femur (mineralizing) and tail tendon (non-mineralizing) and turkey leg tendon (having both mineralizing and non-mineralizing regions in the same individual specimen). An experimental approach ex vivo was designed for this investigation by combining sequential protein extraction with comprehensive protein mapping using proteomics and Western blotting. The extraction method enabled separation of various NCPs based on their association with either the extracellular organic collagenous matrix phases or the inorganic mineral phases of the tissues. The proteomics work generated a complete picture of NCPs in different tissues and animal species. Subsequently, Western blotting provided validation for some of the proteomics findings. The survey then yielded generalized results relevant to various protein families, rather than only individual NCPs. This study focused primarily on the NCPs belonging to the small leucine-rich proteoglycan (SLRP) family and the small integrin-binding ligand N-linked glycoproteins (SIBLINGs). SLRPs were found to be associated only with the collagenous matrix, a result suggesting that they are mainly involved in structural matrix organization and not in mineralization. SIBLINGs as well as matrix Gla (γ-carboxyglutamate) protein were strictly localized within the inorganic mineral phase of mineralizing tissues, a finding suggesting that their roles are limited to mineralization. The results from this study indicated that osteocalcin was closely involved in mineralization but did not preclude possible additional roles as a hormone. This report provides for the first time a spatial survey and comparison of NCPs from mineralizing and non-mineralizing tissues ex vivo and defines the proteome of turkey leg tendons as a model for vertebrate mineralization.

Radiation-induced heart disease (RIHD), a common side effect of chest irradiation, is a primary cause of mortality among patients surviving thoracic cancer. Thus, the development of novel, clinically applicable cardioprotective agents which can alleviate the harmful effects of irradiation on the heart is of great importance in the field of experimental oncocardiology. Biglycan and decorin are structurally related small leucine-rich proteoglycans which have been reported to exert cardioprotective properties in certain cardiovascular pathologies. Therefore, in the present study we aimed to examine if biglycan or decorin can reduce radiation-induced damage of cardiomyocytes. A single dose of 10 Gray irradiation was applied to induce radiation-induced cell damage in H9c2 cardiomyoblasts, followed by treatment with either biglycan or decorin at various concentrations. Measurement of cell viability revealed that both proteoglycans improved the survival of cardiac cells post-irradiation. The cardiocytoprotective effect of both biglycan and decorin involved the alleviation of radiation-induced proapoptotic mechanisms by retaining the progression of apoptotic membrane blebbing and lowering the number of apoptotic cell nuclei and DNA double-strand breaks. Our findings provide evidence that these natural proteoglycans may exert protection against radiation-induced damage of cardiac cells.

Decorin (DCN), a member of the small leucine-rich proteoglycan gene family, is secreted from stromal fibroblasts with non-cell-autonomous anti-breast-cancer effects. Therefore, in the present study, we sought to elucidate the function of decorin in breast stromal fibroblasts (BSFs). We first showed DCN downregulation in active cancer-associated fibroblasts (CAFs) compared to their adjacent tumor counterpart fibroblasts at both the mRNA and protein levels. Interestingly, breast cancer cells and the recombinant IL-6 protein, both known to activate fibroblasts in vitro, downregulated DCN in BSFs. Moreover, specific DCN knockdown in breast fibroblasts modulated the expression/secretion of several CAF biomarkers and cancer-promoting proteins (α-SMA, FAP- α, SDF-1 and IL-6) and enhanced the invasion/proliferation abilities of these cells through activation of the STAT3/AUF1 signaling. Furthermore, DCN-deficient fibroblasts promoted the epithelial-to-mesenchymal transition and stemness processes in BC cells in a paracrine manner, which increased their resistance to cisplatin. These DCN-deficient fibroblasts also enhanced angiogenesis and orthotopic tumor growth in mice in a paracrine manner. On the other hand, ectopic expression of DCN in CAFs suppressed their active features and their paracrine pro-carcinogenic effects. Together, the present findings indicate that endogenous DCN suppresses the pro-carcinogenic and pro-metastatic effects of breast stromal fibroblasts.

Background: The interplay between gut microbiota and tumor microenvironment (TME) in the pathogenesis of colorectal cancer (CRC) is largely unknown. Here, we elucidated the functional role of B. adolescentis and its possible mechanism on the manipulation of Decorin+ macrophages in colorectal cancer. Methods: The relative abundance of B. adolescentis in tumor or para-tumor tissue of CRC patients was analyzed. The role of B. adolescentis was explored in the CRC animal models. The single cell-RNA sequencing (scRNA-seq) was used to investigate the myeloid cells subsets in TME. The expression level of TLR2/YAP axis and its downstream Decorin in macrophages were tested by Western blot and qRT-PCR. Knockdown of Decorin in Raw264.7 was performed to investigate the effect of Decorin+ macrophages on subcutaneous tumor formation. Multi-immunofluorescence assay examined the number of Decorin+ macrophages on the CRC tissue. Results: We found that the abundance of B. adolescentis was significantly reduced in tumor tissue of CRC patients. Supplementation with B. adolescentis suppressed AOM/DSS-induced tumorigenesis in mice. ScRNA-seq and animal experiment revealed that B. adolescentis increased Decorin+ macrophages. Mechanically, Decorin was activated by TLR2/YAP axis in macrophages. The abundance of B. adolescentis was correlated with the number of Decorin+ macrophages and the expression level of TLR2 in tumor tissue of CRC patients. Conclusions: These results highlight that B. adolescentis induced Decorin+ macrophages and provide a novel therapeutic target for probiotic-based modulation of immune microenvironment in CRC. [ABSTRACT FROM AUTHOR]