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Abstract Background Chronic ER stress and dysfunction is a hallmark of obesity and a critical contributor to metaflammation, abnormal hormone action and altered substrate metabolism in metabolic tissues, such as liver and adipocytes. Lack of STAMP2 in lean mice induces inflammation and insulin resistance on a regular diet, and it is dysregulated in the adipose tissue of obese mice and humans. We hypothesized that the regulation of STAMP2 is disrupted by ER stress. Methods 3T3-L1 and MEF adipocytes were treated with ER stress inducers thapsigargin and tunicamycin, and inflammation inducer TNFα. The treatments effect on STAMP2 expression and enzymatic function was assessed. In addition, 3T3-L1 adipocytes and HEK cells were utilized for Stamp 2 promoter activity investigation performed with luciferase and ChIP assays. Results ER stress significantly reduced both STAMP2 mRNA and protein expression in cultured adipocytes whereas TNFα had the opposite effect. Concomitant with loss of STAMP2 expression during ER stress, intracellular localization of STAMP2 was altered and total iron reductase activity was reduced. Stamp 2 promoter analysis by reporter assays and chromatin immunoprecipitation, showed that induction of ER stress disrupts C/EBPα-mediated STAMP2 expression. Conclusion These data suggest a clear link between ER stress and quantitative and functional STAMP2-deficiency. Highlights • STAMP2 is of importance in the understanding of metabolic disease. • ER stress affects STAMP2 expression, distribution, and function in adipocytes. • Loss of C/EBPα binding to Stamp 2 promoter under ER stress decrease STAMP2 levels. • This implicates STAMP2 as a link between ER dysfunction and metabolic disease. [ABSTRACT FROM AUTHOR]

Aim To enhance survival and generation of definitive endoderm cells from human embryonic stem cells in a simple and reproducible system. Main methods Definitive endoderm (DE) differentiation from human embryonic stem cells (hESCs) was induced under a chemical-defined condition withdrawn insulin supplement and serum albumin. We dissected influence of “alternative growth factors”, WNT3A, BMP4 and bFGF in activin A-driven differentiation by detection of DE-associated genes expression and cell viability. Expression of DE-associated SOX17 and FOXA2 genes was analyzed by real time reverse transcription polymerase chain reaction (RT-PCR) and Western blot assays. Quantitative evaluation of DE efficiency was performed by flow cytometry analysis of CXCR4-expressed cell population. Cell viability during DE differentiation was analyzed by an Annexin V/PI double staining test. Key findings Supplementation with WNT3A, BMP4 or bFGF promoted DE generation in a dose- and time-dependent manner. Cell apoptosis elicited by activin A was significantly ameliorated by a cocktail with WNT3A, BMP4 and bFGF. This allowed for sustained cell viability without insulin-containing supplements, thereby indirectly improving the efficiency of DE generation. Therefore, the cocktail containing is optimal for efficient DE generation in the presence of activin A and an insulin/albumin-free condition. Significance This optimal condition facilitates the balance between the productivity and the viability maintenance, and could be valuable for mass production of DE with minimal variation. [ABSTRACT FROM AUTHOR]

Perillaldehyde (PAE), a natural monoterpenoid agent extracted from Perilla frutescence , PAE has been reported to present various physiological capabilities, such as anti-inflammation, anti-oxidative and anti-fungal. In this study, we show that PAE exhibits strong antifungal activity against Candida albicans (C. albicans). C. albicans , a fungal pathogen with high incidence of antifungal resistance in clinical settings, is the major cause of oropharyngeal candidiasis (OPC). OPC is characterized by inflammatory immunological responses to fungal infections. Our in vitro results show PAE inhibited several virulence attributes of C. albicans including biofilm formation, yeast-to-hyphal transition and secreted aspartic proteinases (SAPs) gene expression. Using an experimental murine model of OPC, we found that PAE inhibited NLRP3 inflammasome assembly, reduced the excessive accumulation of ROS and prevented the p65 transfer in nuclear; processes all leading to reduced inflammation burden in the host. Together, this supports use PAE as a promising new agent to improve OPC. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The purpose of this study was to investigate the accuracy of high-frequency ultrasonography in the diagnosis of injuries of medial patellofemoral ligaments (MPFLs), analyse the characteristics of MPFL injury and correlations between injury of the MPFL and articular cartilage of the inferomedial patella in patients with acute traumatic lateral patellar dislocation. Methods: High-frequency sonographic images of 49 patients with acute traumatic lateral patellar dislocations treated surgically were reviewed. The χ 2 tests were performed for statistical analysis. Results: Twenty-eight cases of complete MPFL tear and 21 cases of partial MPFL tear were identified in operation, with 27 cases of MPFL tear located at their femoral attachment, 21 cases of tear at the patellar attachment and one case of midsubstance tear. The diagnostic accuracy of sonography regarding partial MPFL tear and complete MPFL tear was 89.8% and 89.8%. Among the patients with MPFL tear at the patellar attachment, eight and six cases were concomitant with chondral and osteochondral lesions in the inferomedial patella, respectively, in contrast to nine and six cases in patients with MPFL tear at the femoral attachment, respectively. There was no significant difference between the two locations described above regarding the prevalence rates of chondral or osteochondral lesions of the inferomedial patella (P =0.732, P =0.614). Among the patients with complete MPFL tear, 12 and 10 cases were concomitant with chondral and osteochondral lesions in the inferomedial patella, respectively, while six and two cases were concomitant with partial MPFL tear. There was no significant difference between the two types of injuries discussed above on the prevalence rates of chondral lesions of the inferomedial patella (P =0.305), but the prevalence rate of osteochondral lesions between the two types of injuries discussed above was statistically different (P =0.035). Conclusions: The MPFL is most easily injured at the femoral attachment, secondly at the patellar attachment. High-frequency ultrasonography is an accurate method in the diagnosis of an MPFL tear. There are neither significant differences on the prevalence rates of chondral or osteochondral lesions of the inferomedial patella between locations of MPFL injuries, nor significant difference on the prevalence rates of chondral lesions between MPFL injury types; but the complete MPFL tear is more often concomitant with inferomedial patellar osteochondral lesions than the partial MPFL tear. [Copyright &y& Elsevier]