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Purpose: Skeletal muscle has a major influence on whole-body metabolic homeostasis. In the present study, we aimed to determine the metabolic effects of the β 3 adrenergic receptor agonist CL316243 (CL) in the skeletal muscle of high-fat diet-fed rats. Methods: Sprague-Dawley rats were randomly allocated to three groups, which were fed a control diet (C) or a high-fat diet (HF), and half of the latter were administered 1 mg/kg CL by gavage once weekly (HF+CL), for 12 weeks. At the end of this period, the serum lipid profile and glucose tolerance of the rats were evaluated. In addition, the phosphorylation and protein and mRNA expression of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor γ coactivator (PGC)-1α, and carnitine palmitoyl transferase (CPT)-1b in skeletal muscle were measured by Western blot analysis and qPCR. The direct effects of CL on the phosphorylation (p-) and expression of AMPK, PGC-1α, and CPT-1b were also evaluated by Western blotting and immunofluorescence in L6 myotubes. Results: CL administration ameliorated the abnormal lipid profile and glucose tolerance of the high-fat diet-fed rats. In addition, the expression of p-AMPK, PGC-1α, and CPT-1b in the soleus muscle was significantly increased by CL. CL (1 μM) also increased the protein expression of p-AMPK, PGC-1α, and CPT-1b in L6 myotubes. However, the effect of CL on PGC-1α protein expression was blocked by the AMPK antagonist compound C, which suggests that CL increases PGC-1α protein expression via AMPK. Conclusion: Activation of the β 3 adrenergic receptor in skeletal muscle ameliorates the metabolic abnormalities of high-fat diet-fed rats, at least in part via activation of the AMPK/PGC-1α pathway. [ABSTRACT FROM AUTHOR]

Background: Perivascular adipose tissue (PVAT) can regulate vascular homeostasis by secreting various adipokines. This study investigated the effects of PVAT browning on its endocrine function. Methods: In the first section of our study, male Sprague-Dawley rats were randomly divided into cold exposure (8°C) and 24°C acclimation groups. After cold exposure for 7 days, interscapular brown adipose tissue (iBAT), subcutaneous white adipose tissue, thoracic aortic PVAT, and abdominal aortic PVAT (aPVAT) were harvested for histological and brown marker gene expression analysis. In the second part, male rats were fed a high fat diet (HFD) for 10 weeks. In the 11th week, the rats were treated with or without cold exposure. After 14-day cold exposure, aPVAT was collected for histological, gene, and protein expression analysis. Results: Cold exposure had a browning effect on aPVAT by increasing UCP-1 and PGC-1α expression levels. After HFD feeding for 10 weeks, 14-day cold exposure was still able to induce aPVAT browning. Compared with thermoneutrality acclimation rats, TNF-α, IL-6, and p-p65 expression levels were significantly lower in aPVAT from HFD-fed rats with cold exposure. In contrast, p-AMPK expression levels were increased in aPVAT from HFD-fed rats with cold exposure. Conclusions: Our study demonstrated that browning of aPVAT in HFD-fed rats lowered the pro-inflammatory adipokine expression levels and activated AMPK. [ABSTRACT FROM AUTHOR]

Objective: To assess the quality of medical care in childhood-onset systemic lupus erythematosus (SLE) at tertiary pediatric rheumatology centers as measured by observance of SLE quality indicators (SLE-QIs).Methods: International consensus has been achieved for childhood-onset SLE-QIs capturing medical care provision in 9 domains: diagnostic testing, education of cardiovascular (CV) risk and lifestyles, lupus nephritis (LN), medication management, bone health, ophthalmologic surveillance, transition, pregnancy, and vaccination. Using medical record information, the level of performance of these childhood-onset SLE-QIs was assessed in childhood-onset SLE populations treated at 4 tertiary pediatric rheumatology centers in the US, 2 in Brazil, and 1 center in India.Results: A total of 483 childhood-onset SLE patients were assessed. Care for the 310 US patients differed markedly for childhood-onset SLE-QIs addressing LN, bone health, vaccinations, education on CV risk, and transition planning. Performance of safety blood testing for medications was high at all centers. Despite often similar performance on the childhood-onset SLE-QI, access to kidney biopsies was lower in Brazil than in the US. Irrespective of the country of practice, larger centers tended to meet the childhood-onset SLE-QIs more often than smaller centers.Conclusion: The childhood-onset SLE-QIs, evidence-based minimum standards of medical care, are not consistently met in the US or some other countries outside the US. This has the potential to contribute to suboptimal childhood-onset SLE outcomes. [ABSTRACT FROM AUTHOR]

Objective To evaluate the results of orthodontic micro- implant anchorage implantation by application of Spiral CT and three-dimensional reconstruction techniques, so as to explore its application value in assisting clinical diagnosis and treatment. Methods 20 orthodontic patients were implanted with 48 micro- planting screws. SOMATOM Sensation 40/64 helical CT scan was performed. The axial unenhanced helical CT data were given multi-planar reconstruction (MPR), maximum intensity projection (MIP), volume rendering (VR) and surface multidimensional reconstruction (CPR) by using the Siemens 3D post-processing software. The axial scanning images and reconstructed images were compared, observed and analyzed . Results The planting results of 37 micro screws were satisfactory without injuring the vital tissues surrounding the root. The planting results of 11 micro-screw were not ideal, and these micro-screws were observed or reimplanted and got success. Spiral CT axial scan showed better the tooth root interval and the relationship between tooth root and the planting screws. VR can directly showed the overall relationship between the planting screws and teeth, jaw contour appearance. The relationship between the screw and tooth was showed satisfactorily by MIP which could rotate freely and observe from different angles. MPR could clearly show the structural relationships between micro-root planting screws and tooth root and surrounding tissues from the cross section, and could make up for the shortcomings of axial limitations, and was easy to measure the distance and tilt angle of the long axis. Conclusion Spiral CT and three-dimensional reconstruction can accurately show the jaw micro planting screw shape, location and spatial relationships with adjacent teeth, the image is clear, intuitive and definite, and spiral CT and three-dimensional reconstruction has high application value in orthodontics micro-implant anchorage clinic as a powerful auxiliary examination means. [ABSTRACT FROM AUTHOR]

Abstract: Proteasome inhibitors exhibit antitumoral activity against malignancies of different histology. Emerging evidence indicates that antiapoptotic factors may also accumulate as a consequence of exposure to these drugs, thus it seems plausible that activation of survival signaling cascades might compromise their antitumoral effects. Bcl-2-associated athanogene (BAG) family proteins are characterized by their property of interaction with a variety of partners involved in modulating the proliferation/death balance, including heat shock proteins (HSP), Bcl-2, Raf-1. In this report, we demonstrated that BAG3 is a novel antiapoptotic molecule induced by proteasome inhibitors in various cancer cells at the transcriptional level. Moreover, we demonstrated that BAG3 knockdown by siRNA sensitized cancer cells to MG132-induced apoptosis. Taken together, our results suggest that BAG3 induction might represents as an unwanted molecular consequence of utilizing proteasome inhibitors to combat tumors. [Copyright &y& Elsevier]

Background: Congenital nephrotic syndrome (CNS) is characterised by increased proteinuria, hypoproteinemia, and edema beginning in the first 3 months of life. Recently, molecular genetic studies have identified several genes involved in the pathogenesis of CNS. A systematic investigation of the genes for CNS in China has never been performed; therefore, we conducted a mutational analysis in 12 children with CNS,with the children coming from 10 provinces and autonomous regions in China.Methods: Twelve children with CNS were enrolled from 2009 to 2016. A mutational analysis was performed in six children by Sanger sequencing in eight genes (NPHS1, NPHS2, PLCE1, WT1, LAMB2, LMXIB, COQ6 and COQ2) before 2014, and whole-exome sequencing was used from 2014 to 2016 in another six children. Significant variants that were detected by next generation sequencing were confirmed by conventional Sanger sequencing in the patients' families.Results: Of the 12 children, eight patients had a compound heterozygous NPHS1 mutation, one patient had a de novo mutation in the WT1 gene, and another patient with extrarenal symptoms had a homozygous mutation in the COQ6 gene. No mutations were detected in genes NPHS2, PLCE1, LAMB2, LMXIB, and COQ2 in the 12 patients.Conclusions: This study demonstrates that the majority of CNS cases (67%, 8/12 patients) are caused by genetic defects, and the NPHS1 mutation is the most common cause of CNS in Chinese patients. A mutational analysis of NPHS1 should be recommended in Chinese patients with CNS in all exons of NPHS1 and in the intron-exon boundaries. [ABSTRACT FROM AUTHOR]

Background: Primary hyperoxaluria type 1 is a rare autosomal recessive disease of glyoxylate metabolism caused by a defect in the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT) that leads to hyperoxaluria, recurrent urolithiasis, and nephrocalcinosis.Methods: Two unrelated patients with recurrent urolithiasis, along with members of their families, exhibited mutations in the AGXT gene by PCR direct sequencing.Results: Two heterozygous mutations that predict truncated proteins, p.S81X and p.S275delinsRAfs, were identified in one patient. The p.S81X mutation is novel. Two heterozygous missense mutations, p.M1T and p.I202N, were detected in another patient but were not identified in her sibling. These four mutations were confirmed to be of paternal and maternal origin.Conclusions: These are the first cases of primary hyperoxaluria type 1 to be diagnosed by clinical manifestations and AGXT gene mutations in mainland China. The novel p.S81X and p.I202N mutations detected in our study extend the spectrum of known AGXT gene mutations. [ABSTRACT FROM AUTHOR]

Objective. Brown adipose tissue (BAT) dissipates chemical energy to protect against obesity. In the present study, we aimed to determine the effects of Erchen decoction on the lipolysis and thermogenesis function of BAT in high-fat diet-fed rats. Methods. Sprague-Dawley rats were randomly divided into four groups, which were fed a control diet (C) or a high-fat diet (HF), and the latter was administered with high and low doses of Erchen decoction by gavage once a day, for 12 weeks. Body weight, the serum lipid profile, serum glucose, and insulin levels of the rats were evaluated. In addition, the phosphorylation and protein and mRNA expression of AMP-activated protein kinase (AMPK), adipose triglyceride lipase (ATGL), peroxisome proliferator-activated receptor γ coactivator- (PGC-) 1α, and uncoupling protein 1 (UCP-1) in BAT were measured by immunoblotting and RT-PCR. Results. Erchen decoction administration decreased body weight gain and ameliorated the abnormal lipid profile and insulin resistance index of the high-fat diet-fed rats. In addition, the expression of p-AMPK and ATGL in the BAT was significantly increased by Erchen decoction. Erchen decoction also increased the protein and mRNA expression of PGC-1α and UCP-1 in BAT. Conclusion. Erchen decoction ameliorates the metabolic abnormalities of high-fat diet-fed rats, at least in part via activation of lipolysis and thermogenesis in BAT. [ABSTRACT FROM AUTHOR]