PPM1A Controls Diabetic Gene Programming through Directly Dephosphorylating PPAR?? at Ser273

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a master regulator of adipose tissue biology. In obesity, phosphorylation of PPAR gamma at Ser273 (pSer273) by cyclin-dependent kinase 5 (CDK5)/extracellular signal-regulated kinase (ERK) orchestrates diabetic gene reprogramming via dysregulation of specific gene expression. Although many recent studies have focused on the development of non-classical agonist drugs that inhibit the phosphorylation of PPAR gamma at Ser273, the molecular mechanism of PPAR gamma dephosphorylation at Ser273 is not well characterized. Here, we report that protein phosphatase Mg2+/Mn2+-dependent 1A (PPM1A) is a novel PPAR gamma phosphatase that directly dephosphorylates Ser273 and restores diabetic gene expression which is dysregulated by pSer273. The expression of PPM1A significantly decreases in two models of insulin resistance: diet-induced obese (DIO) mice and db/db mice, in which it negatively correlates with pSer273. Transcriptomic analysis using microarray and genotype-tissue expression (GTEx) data in humans shows positive correlations between PPM1A and most of the genes that are dysregulated by pSer273. These findings suggest that PPM1A dephosphorylates PPAR gamma at Ser273 and represents a potential target for the treatment of obesity-linked metabolic disorders

Ovarian Gynandroblastoma with a Juvenile Granulosa Cell Tumor Component in a Postmenopausal Woman: A Case Report and Literature Review

Gynandroblastoma is an extremely rare sex cord-stromal tumor with both female (granulosa cell tumor) and male (Sertoli-Leydig cell tumor) elements. Juvenile granulosa cell tumors are also very rare and are so named because they usually occur in children and adolescents. A 71-year-old woman with right upper quadrant abdominal pain visited our hospital. Pelvic computed tomography showed a large multilocular cystic mass, suspected to be of ovarian origin. We performed a total abdominal hysterectomy (total abdominal hysterectomy was performed) with bilateral salpingo-oophorectomy. A 13-cm multilocular cystic mass with serous fluid was observed in her right ovary. Upon microscopic examination, the solid component of the mass showed both Sertoli-Leydig cell and juvenile granulosa cell differentiation, which we diagnosed as gynandroblastoma. Gynandroblastoma with a juvenile granulosa cell tumor component is extremely rare and, until now, only six cases have been reported in the English literature. We report the first gynandroblastoma with a juvenile granulosa cell tumor component diagnosed in an elderly patient, along with a literature review

In-Plane Strengthening of Unreinforced Masonry Walls by Glass Fiber-Reinforced Polyurea

Strengthening techniques have been employed in Korea to unreinforced masonry walls (UMWs) for several years to protect them from damage caused by the intermittent occurrence of earthquakes. Polyurea, which has a high tensile strength and elongation rate, can be utilized as a strengthening material to enhance the in-plane strength and ductility of UMWs. Glass fiber-reinforced polyurea (GFRPU) is a composite elastomer manufactured by progressively adding milled glass fiber to polyurea. The purpose of this study is to investigate the enhancement of the in-plane strength and ductility of UMWs using GFRPU, depending on the shape of the GFRPU coating on the wall. Four masonry wall specimens are tested with test variables of the number of strengthening sides and coating shapes. It is illustrated that the GFRPU reinforcement of masonry wall leads to enhanced load-carrying capacity, ductility, and energy absorption. An empirical formula to represent the degree of strengthening effected by GFRPU is proposed in this study. Doi: 10.28991/cej-2021-03091782 Full Text: PD

Out-of-Plane Strengthening of Unreinforced Masonry Walls by Glass Fiber-Reinforced Polyurea

Fiber-reinforced polymer reinforcement or polyurea reinforcement techniques are applied to strengthen unreinforced masonry walls (UMWs). The purpose of this experimental study is to verify the out-of-plane reinforcing effect of sprayed glass fiber-reinforced polyurea (GFRPU), which is a composite elastomer made of polyurea and milled glass fibers on UMW. The out-of-plane strengths and ductile behaviors based on various coating shapes are compared in this study. An empirical formula to describe the degree of reinforcement on the out-of-plane strength of the UMW is derived based on the experimental results. It is observed that the peak load-carrying capacity, ductility, and energy absorption capacity gradually improve with an increase in the strengthening degree or area. Compared with the existing masonry wall reinforcement method, the GFRPU technique is a construction method that can help improve the safety performance along with ease of construction and economic efficiency. Doi: 10.28991/CEJ-2022-08-01-011 Full Text: PD

Mycobacterium abscessus activates the NLRP3 inflammasome via Dectin-1–Syk and p62/SQSTM1

Numerous atypical mycobacteria, including Mycobacterium abscessus (Mabc), cause nontuberculous mycobacterial infections, which present a serious public health threat. Inflammasome activation is involved in host defense and the pathogenesis of autoimmune diseases. However, inflammasome activation has not been widely characterized in human macrophages infected with atypical mycobacteria. Here, we demonstrate that Mabc robustly activates the nucleotide binding and oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome via dectin-1/Syk-dependent signaling and the cytoplasmic scaffold protein p62/SQSTM1 (p62) in human macrophages. Both dectin-1 and Toll-like receptor 2 (TLR2) were required for Mabc-induced mRNA expression of pro-interleukin (IL)-1β, cathelicidin human cationic antimicrobial protein-18/LL-37 and β-defensin 4 (DEFB4). Dectin-1-dependent Syk signaling, but not that of MyD88, led to the activation of caspase-1 and secretion of IL-1β through the activation of an NLRP3/apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) inflammasome. Additionally, potassium efflux was required for Mabc-induced NLRP3/ASC inflammasome activation. Furthermore, Mabc-induced p62 expression was critically involved in NLRP3 inflammasome activation in human macrophages. Finally, NLRP3/ASC was critical for the inflammasome in antimicrobial responses to Mabc infection. Taken together, these data demonstrate the induction mechanism of the NLRP3/ASC inflammasome and its role in innate immunity to Mabc infection

Efficacy and Safety of Autologous Stromal Vascular Fraction in the Treatment of Empty Nose Syndrome

Objectives Regenerative treatment using stem cells may serve as treatment option for empty nose syndrome (ENS), which is caused by the lack of turbinate tissue and deranged nervous system in the nasal cavity. We aimed to assess the efficacy and safety of the autologous stromal vascular fraction (SVF) in the treatment of ENS. Methods In this prospective observational clinical study, we enrolled 10 ENS patients who volunteered to undergo treatment of ENS through the injection of autologous SVF. Data, including demographic data, pre- and postoperative Sino-Nasal Outcome Test-25 (SNOT-25) scores, overall patient satisfaction, and postoperative complications, were prospectively collected. Nasal secretion was assessed using the polyurethane foam absorption method, and the levels of biological markers were analyzed in both ENS group and control group using enzyme-linked immunosorbent assay. The SVF extracted from abdominal fat was diluted and injected into both inferior turbinates. Results Among the 10 initial patients, one was excluded from the study. Subjective satisfaction was rated as “much improved” in two and “no change” in seven. Among the improved patients, the mean preinjection SNOT-25 score was 55.0 and the score at 6 months after injection was 19.5. However, the average SNOT-25 score of nine participants at 6 months after injection (mean±standard deviation, 62.4±35.8) did not differ significantly from the baseline SNOT25 score (70.1±24.7, P>0.05, respectively). Among the various inflammatory markers assessed, the levels of interleukin (IL)-1β, IL-8, and calcitonin gene-related peptide were significantly higher in ENS patients. Compared with preinjection secretion level, the nasal secretions from SVF-treated patients showed decreased expressions of IL-1β and IL-8 after injection. Conclusion Although SVF treatment appears to decrease the inflammatory cytokine levels in the nasal mucosa, a single SVF injection was not effective in terms of symptom improvement and patient satisfaction. Further trials are needed to identify a more practical and useful regenerative treatment modality for patients with ENS

Cell-free synthesis of functional phospholipase A1 from Serratia sp.

Additional file 1: Figure S1 Gas chromatography analysis of sesame oil incubated with cell-free synthesized PLA1