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Scientific Reports Jun 2023Aerobic training (AT) is suggested to be an effective anti-aging strategy for skin aging. However, the respective effects of resistance training (RT) have not been...
Aerobic training (AT) is suggested to be an effective anti-aging strategy for skin aging. However, the respective effects of resistance training (RT) have not been studied. Therefore, we compared the effects of AT and RT on skin aging in a 16-week intervention in 61 healthy sedentary middle-aged Japanese women. Data from 56 women were available for analysis. Both interventions significantly improved skin elasticity and upper dermal structure, and RT also improved dermal thickness. After the training intervention, expression of dermal extracellular matrix-related genes was increased in normal human primary dermal fibroblasts. AT and RT had different effects on circulating levels of factors, such as cytokines, hormones in serum, and metabolites, and RT increased dermal biglycan (BGN). To our knowledge, this is the first report to show different effects of AT and RT on skin aging and identify the key factors involved in RT-induced skin rejuvenation.
Topics: Middle Aged; Humans; Female; Skin Aging; Resistance Training; Skin; Extracellular Matrix; Aging; Fibroblasts
PubMed: 37353523
DOI: 10.1038/s41598-023-37207-9 -
Journal of Lipid Research Jan 2024Increased circulating levels of apolipoprotein C3 (APOC3) predict cardiovascular disease (CVD) risk in humans, and APOC3 promotes atherosclerosis in mouse models.... (Review)
Review
Increased circulating levels of apolipoprotein C3 (APOC3) predict cardiovascular disease (CVD) risk in humans, and APOC3 promotes atherosclerosis in mouse models. APOC3's mechanism of action is due in large part to its ability to slow the clearance of triglyceride-rich lipoproteins (TRLs) and their remnants when APOC3 is carried by these lipoproteins. However, different pools and forms of APOC3 exert distinct biological effects or associations with atherogenic processes. Thus, lipid-free APOC3 induces inflammasome activation in monocytes whereas lipid particle-bound APOC3 does not. APOC3-enriched LDL binds better to the vascular glycosaminoglycan biglycan than does LDL depleted of APOC3. Patterns of APOC3 glycoforms predict CVD risk differently. The function of APOC3 bound to HDL is largely unknown. There is still much to learn about the mechanisms of action of different forms and pools of APOC3 in atherosclerosis and CVD, and whether APOC3 inhibition would prevent CVD risk in patients on LDL-cholesterol lowering medications.
Topics: Mice; Animals; Humans; Apolipoprotein C-III; Lipoproteins; Triglycerides; Atherosclerosis
PubMed: 37972731
DOI: 10.1016/j.jlr.2023.100475 -
Frontiers in Oncology 2023Exit of quiescent disseminated cancer cells from dormancy is thought to be responsible for metastatic relapse and a better understanding of dormancy could pave the way...
Exit of quiescent disseminated cancer cells from dormancy is thought to be responsible for metastatic relapse and a better understanding of dormancy could pave the way for novel therapeutic approaches. We used an model of triple negative breast cancer brain metastasis to identify differences in transcriptional profiles between dormant and proliferating cancer cells in the brain. gene, encoding a small proteoglycan biglycan, was strongly upregulated in dormant cancer cells . expression was significantly downregulated in patient brain metastases as compared to the matched primary breast tumors and overexpression in cancer cells inhibited their growth and . Dormant cancer cells were further characterized by a reduced expression of glycolysis genes , and inhibition of glycolysis resulted in a reversible growth arrest reminiscent of dormancy. Our study identified mechanisms that could be targeted to induce/maintain cancer dormancy and thereby prevent metastatic relapse.
PubMed: 37456245
DOI: 10.3389/fonc.2023.1191980 -
Neurobiology of Disease Oct 2023Stroke is the second leading cause of death worldwide and has two major subtypes: ischemic stroke and hemorrhagic stroke. Neuroinflammation is a pathological hallmark of... (Review)
Review
Stroke is the second leading cause of death worldwide and has two major subtypes: ischemic stroke and hemorrhagic stroke. Neuroinflammation is a pathological hallmark of ischemic stroke and intracerebral hemorrhage (ICH), contributing to the extent of brain injury but also in its repair. Neuroinflammation is intricately linked to the extracellular matrix (ECM), which is profoundly altered after brain injury and in aging. In the early stages after ischemic stroke and ICH, immune cells are involved in the deposition and remodeling of the ECM thereby affecting processes such as blood-brain barrier and cellular integrity. ECM components regulate leukocyte infiltration into the central nervous system, activate a variety of immune cells, and induce the elevation of matrix metalloproteinases (MMPs) after stroke. In turn, excessive MMPs may degrade ECM into components that are pro-inflammatory and injurious. Conversely, in the later stages after stroke, several ECM molecules may contribute to tissue recovery. For example, thrombospondin-1 and biglycan may promote activity of regulatory T cells, inhibit the synthesis of proinflammatory cytokines, and aid regenerative processes. We highlight these roles of the ECM in ischemic stroke and ICH and discuss their potential cellular and molecular mechanisms. Finally, we discuss therapeutics that could be considered to normalize the ECM in stroke. Our goal is to spur research on the ECM in order to improve the prognosis of ischemic stroke and ICH.
Topics: Humans; Ischemic Stroke; Neuroinflammatory Diseases; Cerebral Hemorrhage; Stroke; Brain Injuries; Extracellular Matrix
PubMed: 37683956
DOI: 10.1016/j.nbd.2023.106282 -
IScience Sep 2023Biglycan (BGN) is a proteoglycan with branch chains and highly expressed in enteric neurons in the tumor tissue of colorectal cancer (CRC), which is negatively...
Biglycan (BGN) is a proteoglycan with branch chains and highly expressed in enteric neurons in the tumor tissue of colorectal cancer (CRC), which is negatively associated with survival rates in patients with CRC. However, how the proteoglycan promotes the progress of CRC through interacting with bacteria and regulating the immune response of enteric neurons remains largely unknown. In the present study, we found that biglycan deficiency changed tumor distribution in a colitis-associated colon cancer model. Furthermore, we revealed that BGN deficiency inhibits tumor growth in an allograft tumor model and the migration of cancer cell by upregulating interleukin-10 expression in enteric neurons. Significantly, we demonstrated that biglycan deficiency enriched the abundance of through competing with it for chondroitin sulfate to inhibit CRC progress. Our work provided new insights into the interaction between host proteoglycan and gut microbiota as well as the role of enteric neurons in the tumor microenvironment.
PubMed: 37664615
DOI: 10.1016/j.isci.2023.107515 -
Journal of Clinical Medicine Apr 2024The etiopathogenesis of ACL rupture is not clarified. The aim of this study is to identify genomic regions and genetic variants relevant to anterior cruciate ligament... (Review)
Review
BACKGROUND
The etiopathogenesis of ACL rupture is not clarified. The aim of this study is to identify genomic regions and genetic variants relevant to anterior cruciate ligament injury susceptibility that could be involved in non-contact anterior cruciate ligament ruptures.
METHODS
A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines with a PRISMA checklist and algorithm. A search of PubMed, MEDLINE, CINAHL, Cochrane, EMBASE, and Google Scholar databases was conducted using combinations of the terms "anterior cruciate ligament", "ACL", "rupture", "genetics", "single nucleotide polymorphisms", and "SNP" since the inception of the databases until 2021.
RESULTS
Twenty-three studies were included. A total of 7724 patients were analyzed. In total, 3477 patients had ACL ruptures and 4247 patients were controls. Genetic variants in genes encoding for collagens, elastin, fibrillin, matrix metalloproteinases, proteoglycans, angiogenesis-associated signaling cascade proteins, growth differentiation factors, tissue inhibitors of metalloproteases, interleukins, and fibrinogen were analyzed.
CONCLUSION
Findings regarding the association between genes encoding for collagen (COL3A1, COL1A1, and COL12A1), aggrecan (ACAN), decorin (DCN), matrix metalloproteinase (MMP3), interleukin 6 (IL-6), vascular endothelial growth factor A (VEGFA), biglycan (BGN), fibrinogen (FGB), and ACL injuries were found to be inconclusive. Additional evidence is required in order to establish substantial conclusions regarding the association between genetic variants and ACL rupture.
PubMed: 38673603
DOI: 10.3390/jcm13082330 -
International Journal of Molecular... Jun 2023Proteoglycans are vital components of the extracellular matrix in articular cartilage, providing biomechanical properties crucial for its proper functioning. They are... (Review)
Review
Proteoglycans are vital components of the extracellular matrix in articular cartilage, providing biomechanical properties crucial for its proper functioning. They are key players in chondral diseases, specifically in the degradation of the extracellular matrix. Evaluating proteoglycan molecules can serve as a biomarker for joint degradation in osteoarthritis patients, as well as assessing the quality of repaired tissue following different treatment strategies for chondral injuries. Despite ongoing research, understanding osteoarthritis and cartilage repair remains unclear, making the identification of key molecules essential for early diagnosis and effective treatment. This review offers an overview of proteoglycans as primary molecules in articular cartilage. It describes the various types of proteoglycans present in both healthy and damaged cartilage, highlighting their roles. Additionally, the review emphasizes the importance of assessing proteoglycans to evaluate the quality of repaired articular tissue. It concludes by providing a visual and narrative description of aggrecan distribution and presence in healthy cartilage. Proteoglycans, such as aggrecan, biglycan, decorin, perlecan, and versican, significantly contribute to maintaining the health of articular cartilage and the cartilage repair process. Therefore, studying these proteoglycans is vital for early diagnosis, evaluating the quality of repaired cartilage, and assessing treatment effectiveness.
Topics: Humans; Aggrecans; Cartilage, Articular; Decorin; Extracellular Matrix Proteins; Biglycan; Osteoarthritis; Cartilage Diseases; Lectins, C-Type
PubMed: 37446002
DOI: 10.3390/ijms241310824 -
Cancers Jul 2023Cancer development is a multifactorial procedure that involves changes in the cell microenvironment and specific modulations in cell functions. A tumor microenvironment... (Review)
Review
Cancer development is a multifactorial procedure that involves changes in the cell microenvironment and specific modulations in cell functions. A tumor microenvironment contains tumor cells, non-malignant cells, blood vessels, cells of the immune system, stromal cells, and the extracellular matrix (ECM). The small leucine-rich proteoglycans (SLRPs) are a family of nineteen proteoglycans, which are ubiquitously expressed among mammalian tissues and especially abundant in the ECM. SLRPs are divided into five canonical classes (classes I-III, containing fourteen members) and non-canonical classes (classes IV-V, including five members) based on their amino-acid structural sequence, chromosomal organization, and functional properties. Variations in both the protein core structure and glycosylation status lead to SLRP-specific interactions with cell membrane receptors, cytokines, growth factors, and structural ECM molecules. SLRPs have been implicated in the regulation of cancer growth, motility, and invasion, as well as in cancer-associated inflammation and autophagy, highlighting their crucial role in the processes of carcinogenesis. Except for the class I SLRP decorin, to which an anti-tumorigenic role has been attributed, other SLPRs' roles have not been fully clarified. This review will focus on the functions of the class I and II SLRP members biglycan and lumican, which are correlated to various aspects of cancer development.
PubMed: 37509212
DOI: 10.3390/cancers15143549 -
Journal of Clinical Research in... Jan 2024In animal models of obesity, adipocyte-derived versican, and macrophage-derived biglycan play a crucial role in mediating adipose tissue inflammation. We aimed to...
OBJECTIVE
In animal models of obesity, adipocyte-derived versican, and macrophage-derived biglycan play a crucial role in mediating adipose tissue inflammation. We aimed to investigate the levels of versican and biglycan in obese children and their potential association with body adipose tissue and hepatosteatosis.
METHODS
Serum levels of versican, biglycan, IL-6, and hsCRP were measured using the ELISA method. The fat deposition in the liver, spleen, and subcutaneous adipose tissue was calculated using the IDEAL-IQ sequences of MRI. Bioimpedance analysis was performed using the Tanita BC 418 MA device.
RESULTS
The study included 36 obese and 30 healthy children. Serum levels of versican, hsCRP, and IL-6 were higher in the obese group, while no significant difference was found in biglycan levels between the groups. There was a positive correlation between versican, biglycan, hsCRP, and IL-6. The MRI revealed higher segmental and global hepatic steatosis in obese children. There was no relationship between the hepatic fat content and versican, biglycan, IL-6, and hsCRP. Versican, biglycan, hsCRP, and IL-6 were not predictive of hepatosteatosis. Body fat percentage >32% provided a predictive sensitivity of 81.8% and a specificity of 70.5% for hepatosteatosis (AUC: 0.819, p<0.001). Similarly, a BMI SDS >1.75 yielded a predictive sensitivity of 81.8% and a specificity of 69.8% for predicting hepatosteatosis (AUC: 0.789, p<0.001).
CONCLUSION
Obese children have higher levels of versican, hsCRP, and IL-6, and more fatty liver than their healthy peers. Body fat percentage and BMI SDS were the best predictors for hepatosteatosis in these children.
PubMed: 38238969
DOI: 10.4274/jcrpe.galenos.2024.2023-9-18 -
Proceedings of the National Academy of... Apr 2024The complex interplay between malignant cells and the cellular and molecular components of the tumor stroma is a key aspect of cancer growth and development. These...
The complex interplay between malignant cells and the cellular and molecular components of the tumor stroma is a key aspect of cancer growth and development. These tumor-host interactions are often affected by soluble bioactive molecules such as proteoglycans. Decorin, an archetypical small leucine-rich proteoglycan primarily expressed by stromal cells, affects cancer growth in its soluble form by interacting with several receptor tyrosine kinases (RTK). Overall, decorin leads to a context-dependent and protracted cessation of oncogenic RTK activity by attenuating their ability to drive a prosurvival program and to sustain a proangiogenic network. Through an unbiased transcriptomic analysis using deep RNAseq, we identified that decorin down-regulated a cluster of tumor-associated genes involved in lymphatic vessel (LV) development when systemically delivered to mice harboring breast carcinoma allografts. We found that Lyve1 and Podoplanin, two established markers of LVs, were markedly suppressed at both the mRNA and protein levels, and this suppression correlated with a significant reduction in tumor LVs. We further identified that soluble decorin, but not its homologous proteoglycan biglycan, inhibited LV sprouting in an ex vivo 3D model of lymphangiogenesis. Mechanistically, we found that decorin interacted with vascular endothelial growth factor receptor 3 (VEGFR3), the main lymphatic RTK, and its activity was required for the decorin-mediated block of lymphangiogenesis. Finally, we identified that Lyve1 was in part degraded via decorin-evoked autophagy in a nutrient- and energy-independent manner. These findings implicate decorin as a biological factor with antilymphangiogenic activity and provide a potential therapeutic agent for curtailing breast cancer growth and metastasis.
Topics: Decorin; Lymphangiogenesis; Animals; Mice; Humans; Female; Breast Neoplasms; Lymphatic Vessels; Cell Line, Tumor; Disease Progression; Vesicular Transport Proteins; Membrane Glycoproteins; Gene Expression Regulation, Neoplastic
PubMed: 38652741
DOI: 10.1073/pnas.2317760121