Increased expression of collagens, transforming growth factor-β1, and -β3 in gluteal muscle contracture

<p>Abstract</p> <p>Backgroud</p> <p>Gluteal muscle contracture (GMC) is a multi-factor human chronic fibrotic disease of the gluteal muscle. Fibrotic tissue is characterized by excessive accumulation of collagen in the muscle's extracellular matrix. Transforming growth factor (TGF)-β1 and -β2 are thought to play an important role in fibrogenesis, while TGF-β3 is believed to have an anti-fibrotic function. We hypothesize that the expression of collagen and TGF-βs would be up-regulated in GMC patients.</p> <p>Methods</p> <p>The expression of collagen type I, type III and TGF-βs were studied in 23 fibrotic samples and 23 normal/control samples in GMC patients using immunohistochemistry, reverse transcription and polymerase chain reaction (RT-PCR) and western bolt analysis.</p> <p>Results</p> <p>Compared to the unaffected adjacent muscle, increased expression of TGF-β1 and -β3 was associated with deposition of collagen type I and type III in the fibrotic muscle of the GMC patients at the mRNA level. Strong up-regulation of these proteins in fibrotic muscle was confirmed by immunohistochemical staining and western blot analysis. TGF-β2 was not up-regulated in relation to GMC.</p> <p>Conclusion</p> <p>This study confirmed our hypothesis that collagen types I, III, TGF-β1 and TGF-β3 were up-regulated in biopsy specimens obtained from patients with GMC. Complex interaction of TGF-β1 with profibrotic function and TGF-β3 with antifibrotic function may increase synthesis of collagens and thereby significantly contribute to the process of gluteal muscle scarring in patients with GMC.</p

Stochastic Linear-quadratic Control Problems with Affine Constraints

In this paper, we investigate the stochastic linear-quadratic control problems with affine constraints in random coefficients case. With the help of the Pontryagin maximum principle and stochastic Riccati equation, the dual problem of original problem is established and the feedback solution of the optimal control problem is obtained. Under the Slater condition, the equivalence is proved between the solutions to the original problem and the ones of the dual problem, and the KKT condition is also provided for the dual problem. Finally, an invertibility assumption is given for ensuring the uniqueness of the solutions to the dual problem

Vibration characteristics and modal analysis of a grinding machine

The machine industry has undergone several developments in the past years, and reducing the cost and time required for machine designing is important. In this study, the vibration characteristics of a precision grinding machine were obtained through experimental modal analysis and finite element analysis. The experimental modal analysis employed single point excitation, and the equipment used to determine the frequency response of the grinding machine comprised a hammer, an accelerometer, and a spectrum analyzer. In addition, the resonance frequency, damping factor, and modal shape of the grinding machine were determined. The natural frequency, modal shape, and interface stiffness were determined through finite element analysis. Finally, the theoretical model and the experimental modal analysis models were compared, and get closer to the actual situation of a model to conduct several times analysis. Thus, this paper presents a reliable and convenient method to study the characteristics of machine tools; this method can reduce unnecessary costs and find structural weaknesses in machine designs for improvement

Electrochemical detection of non-esterified fatty acid by layer-by-layer assembled enzyme electrodes

AbstractIn this study, detection and measurement of non-esterified fatty acids (NEFA) concentration has been achieved by electrochemical method in one operation step. Multilayer films of poly(dimethyldiallyammonium chloride) (PDA) wrapped multi-wall carbon nanotubes (MWCNTs) and two enzymes acyl-CoA synthetase (ACS) and acyl-CoA oxidase (ACOD) were assembled on a carbon screen printed electrode by the layer-by-layer (LbL) immobilization. The fine polymer–enzyme layers produced by the LbL method, allowed mass transport from the reactant cascading down the layers to accomplish the two-step enzyme reactions. The polymer–CNTs and enzyme modified electrode exhibited good electrocatalytical property retaining enzyme activity. Linear increase of anodic current from H2O2 produced from NEFA oxidation was observed with the increasing concentrations of oleic acid. These results indicate a promising technique for a simple, rapid one-step determination of NEFA for diabetes management

Deletion of CD44 promotes adipogenesis by regulating PPARɣ and cell cycle-related pathways

CD44, a cell surface adhesion receptor and stem cell biomarker, is recently implicated in chronic metabolic diseases. Ablation of CD44 ameliorates adipose tissue inflammation and insulin resistance in obesity. Here, we investigated cell type specific CD44 expression in human and mouse adipose tissue and further studied how CD44 in preadipocytes regulates adipocyte function. Using Crispr Cas9-mdediated gene deletion and lentivirus-mediated gene re-expression, we discovered that deletion of CD44 promotes adipocyte differentiation and adipogenesis, whereas re-expression of CD44 abolishes this effect and decreases insulin responsiveness and adiponectin secretion in 3T3-L1 cells. Mechanistically, CD44 does so via suppressing Pparg expression. Using quantitative proteomics analysis, we further discovered that cell cycle-regulated pathways were mostly decreased by deletion of CD44. Indeed, re-expression of CD44 moderately restored expression of proteins involved in all phases of the cell cycle. These data were further supported by increased preadipocyte proliferation rates in CD44 deficient cells and re-expression of CD44 diminished this effect. Our data suggest that CD44 plays a crucial role in regulating adipogenesis and adipocyte function possibly through regulating PPARɣ and cell cycle-related pathways. This study provides evidence for the first time that CD44 expressed in preadipocytes plays key roles in regulating adipocyte function outside immune cells where CD44 is primarily expressed. Therefore, targeting CD44 in (pre)adipocytes may provide therapeutic potential to treat obesity-associated metabolic complications

Deletion of CD44 promotes adipogenesis by regulating PPARɣ and cell cycle-related pathways

CD44, a cell surface adhesion receptor and stem cell biomarker, is recently implicated in chronic metabolic diseases. Ablation of CD44 ameliorates adipose tissue inflammation and insulin resistance in obesity. Here, we investigated cell type specific CD44 expression in human and mouse adipose tissue and further studied how CD44 in preadipocytes regulates adipocyte function. Using Crispr Cas9-mdediated gene deletion and lentivirus-mediated gene re-expression, we discovered that deletion of CD44 promotes adipocyte differentiation and adipogenesis, whereas re-expression of CD44 abolishes this effect and decreases insulin responsiveness and adiponectin secretion in 3T3-L1 cells. Mechanistically, CD44 does so via suppressing Pparg expression. Using quantitative proteomics analysis, we further discovered that cell cycle-regulated pathways were mostly decreased by deletion of CD44. Indeed, re-expression of CD44 moderately restored expression of proteins involved in all phases of the cell cycle. These data were further supported by increased preadipocyte proliferation rates in CD44 deficient cells and re-expression of CD44 diminished this effect. Our data suggest that CD44 plays a crucial role in regulating adipogenesis and adipocyte function possibly through regulating PPARɣ and cell cycle-related pathways. This study provides evidence for the first time that CD44 expressed in preadipocytes plays key roles in regulating adipocyte function outside immune cells where CD44 is primarily expressed. Therefore, targeting CD44 in (pre)adipocytes may provide therapeutic potential to treat obesity-associated metabolic complications

Estrogen-mediated gut microbiome alterations influence sexual dimorphism in metabolic syndrome in mice

peer-reviewedBackground Understanding the mechanism of the sexual dimorphism in susceptibility to obesity and metabolic syndrome (MS) is important for the development of effective interventions for MS. Results Here we show that gut microbiome mediates the preventive effect of estrogen (17β-estradiol) on metabolic endotoxemia (ME) and low-grade chronic inflammation (LGCI), the underlying causes of MS and chronic diseases. The characteristic profiles of gut microbiome observed in female and 17β-estradiol-treated male and ovariectomized mice, such as decreased Proteobacteria and lipopolysaccharide biosynthesis, were associated with a lower susceptibility to ME, LGCI, and MS in these animals. Interestingly, fecal microbiota-transplant from male mice transferred the MS phenotype to female mice, while antibiotic treatment eliminated the sexual dimorphism in MS, suggesting a causative role of the gut microbiome in this condition. Moreover, estrogenic compounds such as isoflavones exerted microbiome-modulating effects similar to those of 17β-estradiol and reversed symptoms of MS in the male mice. Finally, both expression and activity of intestinal alkaline phosphatase (IAP), a gut microbiota-modifying non-classical anti-microbial peptide, were upregulated by 17β-estradiol and isoflavones, whereas inhibition of IAP induced ME and LGCI in female mice, indicating a critical role of IAP in mediating the effects of estrogen on these parameters. Conclusions In summary, we have identified a previously uncharacterized microbiome-based mechanism that sheds light upon sexual dimorphism in the incidence of MS and that suggests novel therapeutic targets and strategies for the management of obesity and MS in males and postmenopausal women