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The Journal of Frailty & Aging 2024Population aging might increase the prevalence of undernutrition in older people, which increases the risk of frailty. Numerous studies have indicated that myokines are...
BACKGROUND
Population aging might increase the prevalence of undernutrition in older people, which increases the risk of frailty. Numerous studies have indicated that myokines are released by skeletal myocytes in response to muscular contractions and might be associated with frailty. This study aimed to evaluate whether myokines are biomarkers of frailty in older inpatients with undernutrition.
METHODS
The frailty biomarkers were extracted from the Gene Expression Omnibus and Genecards datasets. Relevant myokines and health-related variables were assessed in 55 inpatients aged ≥ 65 years from the Peking Union Medical College Hospital prospective longitudinal frailty study. Serum was prepared for enzyme-linked immunosorbent assay using the appropriate kits. Correlations between biomarkers and frailty status were calculated by Spearman's correlation analysis. Multiple linear regression was performed to investigate the association between factors and frailty scores.
RESULTS
The prevalence of frailty was 13.21%. The bioinformatics analysis indicated that leptin, adenosine 5'-monophosphate-activated protein kinase (AMPK), irisin, decorin, and myostatin were potential biomarkers of frailty. The frailty group had significantly higher concentrations of leptin, AMPK, and MSTN than the robust group (p < 0.05). AMPK was significantly positively correlated with frailty (p < 0.05). The pre-frailty and frailty groups had significantly lower concentrations of irisin than the robust group (p < 0.05), whereas the DCN concentration did not differ among the groups. Multiple linear regression suggested that the 15 factors influencing the coefficients of association, the top 50% were the ADL score, MNA-SF score, serum albumin concentration, urination function, hearing function, leptin concentration, GDS-15 score, and MSTN concentration.
CONCLUSIONS
Proinflammatory myokines, particularly leptin, myostatin, and AMPK, negatively affect muscle mass and strength in older adults. ADL and nutritional status play major roles in the development of frailty. Our results confirm that identification of frailty relies upon clinical variables, myokine concentrations, and functional parameters, which might enable the identification and monitoring of frailty.
Topics: Humans; Aged; AMP-Activated Protein Kinases; Fibronectins; Frailty; Inpatients; Leptin; Myokines; Myostatin; Prospective Studies; Malnutrition; Biomarkers
PubMed: 38616363
DOI: 10.14283/jfa.2024.9 -
Cells May 2024Radiation-induced heart disease (RIHD), a common side effect of chest irradiation, is a primary cause of mortality among patients surviving thoracic cancer. Thus, the...
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.
Topics: Decorin; Biglycan; Apoptosis; Animals; Myocytes, Cardiac; Rats; Cell Line; Cell Survival; Humans
PubMed: 38786104
DOI: 10.3390/cells13100883 -
Revista Brasileira de Ginecologia E... Dec 2023The serum ischemia modified albumin (IMA), biglycan, and decorin levels of pregnant women who were hospitalized for threatened preterm labor were measured.
OBJECTIVE
The serum ischemia modified albumin (IMA), biglycan, and decorin levels of pregnant women who were hospitalized for threatened preterm labor were measured.
METHODS
Fifty-one consecutive pregnant women with a single pregnancy between the 24 and 36 weeks with a diagnosis of threatened preterm labor were included in the present prospective cohort study.
RESULTS
As a result of multivariate logistic regression analysis for predicting preterm delivery within 24 hours, 48 hours, 7 days, 14 days, ≤ 35 gestational weeks, and ≤ 37 gestational weeks after admission, area under the curve (AUC) (95% confidence interval [CI[) values were 0.95 (0.89-1.00), 0.93 (0.86-0.99), 0.91 (0.83-0.98), 0.92 (0.85-0.99), 0.82 (0.69-0.96), and 0.89 (0.80-0.98), respectively. In the present study, IMA and biglycan levels were found to be higher and decorin levels lower in women admitted to the hospital with threatened preterm labor and who gave preterm birth within 48 hours compared with those who gave birth after 48 hours.
CONCLUSION
In pregnant women admitted to the hospital with threatened preterm labor, the prediction preterm delivery of the combined model created by adding IMA, decorin, and biglycan in addition to the TVS CL measurement was higher than the TVS CL measurement alone.
CLINICAL TRIAL REGISTRATION
The present trial was registered at ClinicalTrials.gov, number NCT04451928.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Premature Birth; Decorin; Prospective Studies; Biomarkers; Biglycan; Serum Albumin; Obstetric Labor, Premature; Ischemia
PubMed: 38141595
DOI: 10.1055/s-0043-1772593 -
Materials Horizons May 2024Understanding the molecular mechanism by which the periodontal ligament (PDL) is maintained uncalcified between two mineralized tissues (cementum and bone) may...
Understanding the molecular mechanism by which the periodontal ligament (PDL) is maintained uncalcified between two mineralized tissues (cementum and bone) may facilitate the functional repair and regeneration of the periodontium complex, disrupted in the context of periodontal diseases. However, research that explores the control of type I collagen (COL I) mineralization fails to clarify the detailed mechanism of regulating spatial collagen mineralization, especially in the periodontium complex. In the present study, decorin (DCN), which is characterized as abundant in the PDL region and rare in mineralized tissues, was hypothesized to be a key regulator in the spatial control of collagen mineralization. The circular dichroism results confirmed that DCN regulated the secondary structure of COL I, and the surface plasmon resonance results indicated that COL I possessed a higher affinity for DCN than for other mineralization promoters, such as DMP-1, OPN, BSP and DSPP. These features of DCN may contribute to blocking intrafibrillar mineralization in COL I fibrils during the polymer-induced liquid-precursor mineralization process when the fibrils are cross-linked with DCN. This effect was more remarkable when the fibrils were phosphorylated by sodium trimetaphosphate, as shown by the observation of a tube-like morphology TEM and mineral sheath SEM. This study enhances the understanding of the role of DCN in mineralization regulation among periodontal tissues. This provides insights for the development of biomaterials for the regeneration of interfaces between soft and hard tissues.
PubMed: 38690683
DOI: 10.1039/d3mh02216a -
Tissue & Cell Apr 2024High-temperature requirement A1 (HtrA1), a multidomain serine protease acting on Extracellular matrix (ECM) rearrangement, is also secreted by osteoblasts and...
High-temperature requirement A1 (HtrA1), a multidomain serine protease acting on Extracellular matrix (ECM) rearrangement, is also secreted by osteoblasts and osteoclasts. Recent and conflicting literature highlights HtrA1's role as a controller of bone remodeling, proposing it as a possible target for pathologies with unbalanced bone resorption, like Osteoporosis (OP). To add knowledge on this molecule function in bone physiopathology, here we compared HtrA1 distribution in the ECM of healthy (H) and OP bone tissue, also examining its localization in the sites of new bone formation. HtrA1 was homogeneously expressed in the mature bone ECM of H tissue showing a 55.6 ± 16.4% of the stained area, with a significant (p=0.0001) decrease in OP percentage stained area (21.1 ± 13.1). Moreover, HtrA1 was present in the endosteum and cells involved in osteogenesis, mainly in those "entrapped" in woven bone, whereas osteocytes in mature lamellar bone were negative. Based on our previous observation in OP tissue of a significantly increased expression of Decorin and Osteocalcin, both involved in bone mineralization and remodeling and equally substrates for HtrA1, we speculate that HtrA1 by controlling the proper amount of Decorin and Osteocalcin favors normal bone maturation and mineralization. Besides, we suggest that late-osteoblasts and pre-osteocytes secrete HtrA1 in the adjacent matrix whilst proceeding with their maturation and that HtrA1 expression is further modified during the remodeling from woven to the lamellar bone. Overall, our data suggest HtrA1 as a positive regulator of bone matrix formation and maturation: its reduced expression in mature OP bone, affecting protein content and distribution, could hamper correct bone remodeling and mineralization.
Topics: Humans; Osteocalcin; Serine Proteases; Bone Matrix; Decorin; High-Temperature Requirement A Serine Peptidase 1; Serine Endopeptidases; Bone and Bones; Extracellular Matrix; Osteoporosis
PubMed: 38367326
DOI: 10.1016/j.tice.2024.102329 -
Journal of Ethnopharmacology May 2024Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide, largely due to the limitations of available therapeutic strategies. The...
ETHNOPHARMACOLOGICAL RELEVANCE
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide, largely due to the limitations of available therapeutic strategies. The traditional Chinese medicine Qizhu Anticancer Prescription (QZACP) can improve the quality of life and prolong the survival time of patients with HCC. However, the precise mechanisms underlying the anti-cancer properties of QZACP remain unclear.
PURPOSE
This study examined the anti-hepatocarcinogenic properties of QZACP, with a specific focus on its influence on the p21-activated secretory phenotype (PASP)-mediated immune surveillance, to elucidate the underlying molecular pathways involved in HCC.
MATERIALS AND METHODS
Cell proliferation was measured using the Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, and clonogenic assays. The cell cycle was evaluated using flow cytometry, and senescence was identified by staining with senescence-associated beta-galactosidase (SA-β-gal). A primary liver cancer model produced by diethylnitrosamine was established in C57 BL/6 mice to assess the tumor-inhibitory effect of QZACP. The liver's pathological characteristics were examined using hematoxylin and eosin staining. PASP screening was performed using GeneCards, DisGeNet, Online Mendelian Inheritance in Man, and The Cancer Genome Atlas databases. Western blot analysis, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and Transwell migration assays were performed.
RESULTS
Serum containing QZACP enhanced p21 expression, triggered cell cycle arrest, accelerated cell senescence, and suppressed cell proliferation in Huh7 and MHCC-97H liver cancer cells. QZACP reduced the quantity and dimensions of liver tumor nodules and enhanced p21 protein expression, SA-β-Gal staining in tumor lesions, and cytotoxic CD8 T cell infiltration. Bioinformatic analyses indicated that PASP factors, including hepatocyte growth factor, decorin (DCN), dermatopontin, C-X-C motif chemokine ligand 14 (CXCL14), and Wnt family member 2 (WNT2), play an important role in the development of HCC. In addition, these factors are associated with the presence of natural killer cells and CD8 T cells within tumors. Western blotting and ELISA confirmed that QZACP increased DCN, CXCL14, and WNT2 levels in tumor tissues and peripheral blood.
CONCLUSIONS
QZACP's suppression of HCC progression may involve cell senescence mediated via p21 upregulation, DCN, CXCL14, and WNT2 secretion, and reversal of the immunosuppressive microenvironment. This study provides insights that can be used in the development of new treatment strategies for HCC.
PubMed: 38823657
DOI: 10.1016/j.jep.2024.118400 -
Cornea May 2024The aims of this study were to construct a mesenchymal stem cell (MSC)-laden in situ-forming hydrogel and study its effects on preventing corneal stromal opacity.
PURPOSE
The aims of this study were to construct a mesenchymal stem cell (MSC)-laden in situ-forming hydrogel and study its effects on preventing corneal stromal opacity.
METHODS
The native gellan gum was modified by high temperature and pressure, and the rabbit bone marrow MSCs were encapsulated before adding Ca 2+ to initiate cross-linking. The effects of the hydrogel on 3D culture and gene expression of the rabbit bone marrow MSCs were observed in vitro. Then, the MSC-hydrogel was used to repair corneal stromal injury in New Zealand white rabbits within 28 days postoperation.
RESULTS
The short-chain gellan gum solution has a very low viscosity (<0.1 Pa·s) that is ideal for encapsulating cells. Moreover, mRNA expressions of 3D-cultured MSCs coding for corneal stromal components (decorin, lumican, and keratocan) were upregulated (by 127.8, 165.5, and 25.4 times, respectively) ( P < 0.05) on day 21 in vitro and were verified by Western blotting results. For the in vivo study, the corneal densitometry of the experimental group was (20.73 ± 1.85) grayscale units which was lower than the other groups ( P < 0.05). The MSC-hydrogel downregulated mRNA expression coding for fibrosis markers (α-smooth muscle actin, vimentin, collagen type 5-α1, and collagen type 1-α1) in the rabbit corneal stroma. Furthermore, some of the 5-ethynyl-2'-deoxyuridine (EdU)-labeled MSCs integrated into the upper corneal stroma and expressed keratocyte-specific antigens on day 28 postoperation.
CONCLUSIONS
The short-chain gellan gum allows MSCs to slowly release to the corneal stromal defect and prevent corneal stromal opacity. Some of the implanted MSCs can integrate into the corneal stroma and differentiate into keratocytes.
Topics: Animals; Rabbits; Hydrogels; Cornea; Corneal Stroma; Corneal Keratocytes; Mesenchymal Stem Cells; Corneal Opacity; Corneal Injuries; Collagen; RNA, Messenger
PubMed: 38289027
DOI: 10.1097/ICO.0000000000003475 -
Journal of Proteomics Apr 2024Lysine succinylation (Ksucc) is a recently identified posttranslational modification that is involved in many diseases. This study examined the role of Ksucc in the...
Lysine succinylation (Ksucc) is a recently identified posttranslational modification that is involved in many diseases. This study examined the role of Ksucc in the pathogenesis of hypertrophic scar (HS). The presence of Ksucc in human skin was measured by immunoblotting. Ksucc occurs in many skin proteins ranging from 25 to 250 kDa, and higher levels of Ksucc are found in HS skin than in normal skin. An immunoaffinity approach coupled with LC-MS/MS was used to characterize the first succinylome of human skin, and 159 Ksucc sites in 79 proteins were identified. Among these, there were 38 increased succinylated sites in 29 proteins but no decreased succinylated sites in HS compared with normal skin. A parallel reaction monitoring assay was performed to validate the results of the succinylome and showed that the levels of Ksucc in decorin and collagens, which are involved in the pathogenesis of HS, were increased in HS than in normal skin. In addition, increasing the level of Ksucc enhanced cell proliferation and upregulated the expression of fibrosis markers (α-SMA, COL1, and COL3) in human skin fibroblasts. Our results provide global insights into the functional role of Ksucc in hypertrophic scarring.
Topics: Humans; Cicatrix, Hypertrophic; Lysine; Proteomics; Chromatography, Liquid; Tandem Mass Spectrometry; Protein Processing, Post-Translational
PubMed: 38460743
DOI: 10.1016/j.jprot.2024.105155 -
Foods (Basel, Switzerland) Sep 2023To investigate the possible degradation of the intramuscular connective tissue (IMCT) with cathepsin L, isolated IMCTs were incubated with purified cathepsin L in vitro....
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 T and T 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 T and T of IMCT were more sensitive than they were at pH 5.5~6.5.
PubMed: 37761226
DOI: 10.3390/foods12183517 -
Cells Apr 2024Decorin (DCN), a member of the small leucine-rich proteoglycan gene family, is secreted from stromal fibroblasts with non-cell-autonomous anti-breast-cancer effects....
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.
Topics: Decorin; Humans; STAT3 Transcription Factor; Female; Signal Transduction; Interleukin-6; Animals; Breast Neoplasms; Mice; Cancer-Associated Fibroblasts; Down-Regulation; Heterogeneous Nuclear Ribonucleoprotein D0; Fibroblasts; Stromal Cells; Cell Line, Tumor; Carcinogenesis; Cell Proliferation; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Breast
PubMed: 38667295
DOI: 10.3390/cells13080680