Garcinia mangostana Suppresses Triacylglycerol Synthesis in Hepatocytes and Enterocytes.

Regulation of diacylglycerol acyltransferase (DGAT) and pancreatic lipase (PL) activities is important in the treatment of triacylglycerol (TG)-related metabolic diseases. Garcinia mangostana, also known as mangosteen, is a traditional medicine ingredient used in the treatment of inflammation in Southeast Asia. In this study, The ethanolic extract of G. mangostana peel inhibited human recombinant DGAT1 and DGAT2, and PL enzyme activities in vitro. The inhibitory activity of DGAT1 and DGAT2 enzymes of four representative bioactive substances in mangosteen was confirmed. In addition, G. mangostana was confirmed to suppress the serum TG levels in C57 mice by inhibiting the absorption and synthesis of TG in the gastrointestinal tract. Through this study, it was revealed that G. mangostana extract could be useful for the prevention and amelioration of TG-related metabolic diseases such as obesity and fatty liver.

Black Ginseng Extract Exerts Potentially Anti-Asthmatic Activity by Inhibiting the Protein Kinase Cθ-Mediated IL-4/STAT6 Signaling Pathway.

Asthma is a chronic inflammatory lung disease that causes respiratory difficulties. Black ginseng extract (BGE) has preventative effects on respiratory inflammatory diseases such as asthma. However, the pharmacological mechanisms behind the anti-asthmatic activity of BGE remain unknown. To investigate the anti-asthmatic mechanism of BGE, phorbol 12-myristate 13-acetate plus ionomycin (PMA/Iono)-stimulated mouse EL4 cells and ovalbumin (OVA)-induced mice with allergic airway inflammation were used. Immune cells (eosinophils/macrophages), interleukin (IL)-4, -5, -13, and serum immunoglobulin E (IgE) levels were measured using an enzyme-linked immunosorbent assay. Inflammatory cell recruitment and mucus secretion in the lung tissue were estimated. Protein expression was analyzed via Western blotting, including that of inducible nitric oxide synthase (iNOS) and the activation of protein kinase C theta (PKCθ) and its downstream signaling molecules. BGE decreased T helper (Th)2 cytokines, serum IgE, mucus secretion, and iNOS expression in mice with allergic airway inflammation, thereby providing a protective effect. Moreover, BGE and its major ginsenosides inhibited the production of Th2 cytokines in PMA/Iono-stimulated EL4 cells. In EL4 cells, these outcomes were accompanied by the inactivation of PKCθ and its downstream transcription factors, such as nuclear factor of activated T cells (NFAT), nuclear factor kappa B (NF-κB), activator of transcription 6 (STAT6), and GATA binding protein 3 (GATA3), which are involved in allergic airway inflammation. BGE also inhibited the activation of PKCθ and the abovementioned transcriptional factors in the lung tissue of mice with allergic airway inflammation. These results highlight the potential of BGE as a useful therapeutic and preventative agent for allergic airway inflammatory diseases such as allergic asthma.

Heart-on-Chip for Combined Cellular Dynamics Measurements and Computational Modeling Towards Clinical Applications.

Organ-on-chip or micro-engineered three-dimensional cellular or tissue models are increasingly implemented in the study of cardiovascular pathophysiology as alternatives to traditional in vitro cell culture. Drug induced cardiotoxicity is a key issue in drug development pipelines, but the current in vitro and in vivo studies suffer from inter-species differences, high costs, and lack of reliability and accuracy in predicting cardiotoxicity. Microfluidic heart-on-chip devices can impose a paradigm shift to the current tools. They can not only recapitulate cardiac tissue level functionality and the communication between cells and extracellular matrices but also allow higher throughput studies conducive to drug screening especially with their added functionalities or sensors that extract disease-specific phenotypic, genotypic, and electrophysiological information in real-time. Such electrical and mechanical components can tailor the electrophysiology and mechanobiology of the experiment to better mimic the in vivo condition as well. Recent advancements and challenges are reviewed in the fabrication, functionalization and sensor assisted mechanical and electrophysiological measurements, numerical and computational modeling of cardiomyocytes' behavior, and the clinical applications in drug screening and disease modeling. This review concludes with the current challenges and perspectives on the future of such organ-on-chip platforms.

A postoperative parathyroid hormone-based algorithm to reduce symptomatic hypocalcemia following completion/total thyroidectomy: A retrospective analysis of 591 patients.

BACKGROUND: An institutional protocol for selective calcium/calcitriol supplementation after completion/total thyroidectomy was established based on the 4-hour postoperative parathyroid hormone level. The aim of this study was to evaluate the outcomes of this protocol 5 years after implementation. METHODS: All patients who underwent completion/total thyroidectomy from January 2012 to December 2016 were reviewed. Predictors of a 4-hour parathyroid hormone level <10 pg/mL and symptomatic hypocalcemia were assessed. RESULTS: Of 591 patients, 448 (76%) had a 4-hour parathyroid hormone ≥10, 72 (12%) had a 4-hour parathyroid hormone of 5-10, and 71 (12%) had a 4-hour parathyroid hormone <5. Hypocalcemic symptoms were infrequent (30/448, 7%) if the 4-hour parathyroid hormone was ≥10; 56% (40/71) of those with a 4-hour parathyroid hormone <5 reported symptoms. With 4-hour parathyroid hormone of 5-10, symptoms were reported in 32 of 72 (44%) patients; supplementation at discharge included calcium (n = 55, 76%), calcium and calcitriol (n = 12, 17%), or none (n = 5, 7%). Ten patients subsequently received calcitriol for persistent symptoms. On multivariate analysis, predictors of 4-hour parathyroid hormone <10 included incidental parathyroidectomy, malignancy, and thyroiditis; predictors of hypocalcemic symptoms included age <55 and 4-hour parathyroid hormone <10. CONCLUSION: After completion/total thyroidectomy, patients with a 4-hour parathyroid hormone ≥10 can be safely discharged without routine supplementation. The addition of calcitriol to calcium supplementation should be strongly considered for patients with a 4-hour parathyroid hormone of 5-10.