Revised Subjects of the Current Korean Oriental Pharmacists' Licensing Examination

This study is designed to draw out new integrated subjects of the Korean Oriental Pharmacists' Licensing Examination (KOPLE). In 2004, for the revision of subjects, we have analyzed the curriculums of the Oriental Pharmacy department, the oriental pharmacist's (OP's) job description book, and the elementary items of KOPLE. We also examined the system of the Chinese Herb Pharmacists' Examination and other health personnel licensing examinations and studied the data of items and compared them with KOPLE. We heard the public opinion on the present KOPLE. We developed a subfield of 18 subjects, a middle category of 188 items, and a small category of 1,026 items. We proposed a new KOPLE that consists of three subjects: basic oriental pharmacy, applied oriental pharmacy, and laws and regulations

Mitochondrial Dysfunction Induces Formation of Lipid Droplets as a Generalized Response to Stress

Lipid droplet (LD) formation is a hallmark of cellular stress. Cells attempt to combat noxious stimuli by switching their metabolism from oxidative phosphorylation to glycolysis, sparing resources in LDs for generating cellular reducing power and for anabolic biosynthesis. Membrane phospholipids are also a source of LDs. To elucidate the formation of LDs, we exposed mice to hyperoxia, hypoxia, myocardial ischemia, and sepsis induced by cecal ligation and puncture (CLP). All the above-mentioned stressors enhanced the formation of LDs, as assessed by transmission electron microscopy, with severe mitochondrial swelling. Disruption of mitochondria by depleting mitochondrial DNA (ρ0 cells) significantly augmented the formation of LDs, causing transcriptional activation of fatty acid biosynthesis and metabolic reprogramming to glycolysis. Heme oxygenase (HO)-1 counteracts CLP-mediated septic shock in mouse models. In HO-1-deficient mice, LD formation was not observed upon CLP, but a concomitant decrease in “LD-decorating proteins” was observed, implying a link between LDs and cytoprotective activity. Collectively, LD biogenesis during stress can trigger adaptive LD formation, which is dependent on mitochondrial integrity and HO-1 activity; this may be a cellular survival strategy, apportioning energy-generating substrates to cellular defense

Carbon monoxide inhibits Fas activating antibody-induced apoptosis in endothelial cells

<p>Abstract</p> <p>Background</p> <p>The extrinsic apoptotic pathway initiates when a death ligand, such as the Fas ligand, interacts with its cell surface receptor (<it>ie</it>., Fas/CD95), forming a death-inducing signaling complex (DISC). The Fas-dependent apoptotic pathway has been implicated in several models of lung or vascular injury. Carbon monoxide, an enzymatic product of heme oxygenase-1, exerts antiapoptotic effects at low concentration <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p>Using mouse lung endothelial cells (MLEC), we examined the antiapoptotic potential of carbon monoxide against apoptosis induced by the Fas/CD95-activating antibody (Jo2). Carbon monoxide was applied to cell cultures <it>in vitro</it>. The expression and/or activation of apoptosis-related proteins and signaling intermediates were determined using Western Immunoblot and co-immunoprecipitation assays. Cell death was monitored by lactate dehydrogenase (LDH) release assays. Statistical significance was determined by student T-test and a value of <it>P </it>< 0.05 was considered significant.</p> <p>Results</p> <p>Treatment of MLEC with Fas-activating antibody (Jo2) induced cell death associated with the formation of the DISC, and activation of caspases (-8, -9, and -3), as well as the pro-apoptotic Bcl-2 family protein Bax. Exposure of MLEC to carbon monoxide inhibited Jo2-induced cell death, which correlated with the inhibition of DISC formation, cleavage of caspases-8, -9, and -3, and Bax activation. Carbon monoxide inhibited the phosphorylation of the Fas-associated death domain-containing protein, as well as its association with the DISC. Furthermore, carbon monoxide induced the expression of the antiapoptotic protein FLIP and increased its association with the DISC.</p> <p>CO-dependent cytoprotection against Fas mediated apoptosis in MLEC depended in part on activation of ERK1/2-dependent signaling.</p> <p>Conclusions</p> <p>Carbon monoxide has been proposed as a potential therapy for lung and other diseases based in part on its antiapoptotic effects in endothelial cells. In vitro, carbon monoxide may inhibit both Fas/caspase-8 and Bax-dependent apoptotic signaling pathways induced by Fas-activating antibody in endothelial cells. Strategies to block Fas-dependent apoptotic pathways may be useful in development of therapies for lung or vascular disorders.</p

Electronic topological transition in sliding bilayer graphene

We demonstrate theoretically that the topology of energy bands and Fermi surface in bilayer graphene undergoes a very sensitive transition when extremely tiny lateral interlayer shift occurs in arbitrary directions. The phenomenon originates from a generation of effective non-Abelian vector potential in Dirac Hamiltonian by the sliding motions. The characteristics of the transition such as pair annihilations of massless Dirac fermions are dictated by the sliding direction owing to a unique interplay between the effective non-Abelian gauge fields and Berry's phases associated with massless electrons. The transition manifests itself in various measurable quantities such as anomalous density of states, minimal conductivity, and distinct Landau level spectrum.Comment: title changed, an extended version for regular article format, 10 pages, 5 figure

Distinct fibroblast subsets regulate lacteal integrity through YAP/TAZ-induced VEGF-C in intestinal villi

Emerging evidence suggests that intestinal stromal cells (IntSCs) play essential roles in maintaining intestinal homeostasis. However, the extent of heterogeneity within the villi stromal compartment and how IntSCs regulate the structure and function of specialized intestinal lymphatic capillary called lacteal remain elusive. Here we show that selective hyperactivation or depletion of YAP/TAZ in PDGFR beta(+) IntSCs leads to lacteal sprouting or regression with junctional disintegration and impaired dietary fat uptake. Indeed, mechanical or osmotic stress regulates IntSC secretion of VEGF-C mediated by YAP/TAZ. Single-cell RNA sequencing delineated novel subtypes of villi fibroblasts that upregulate Vegfc upon YAP/TAZ activation. These populations of fibroblasts were distributed in proximity to lacteal, suggesting that they constitute a peri-lacteal microenvironment. Our findings demonstrate the heterogeneity of IntSCs and reveal that distinct subsets of villi fibroblasts regulate lacteal integrity through YAP/TAZ-induced VEGF-C secretion, providing new insights into the dynamic regulatory mechanisms behind lymphangiogenesis and lymphatic remodeling.Peer reviewe

Gut microbiota regulates lacteal integrity by inducing VEGF-C in intestinal villus macrophages

A lacteal is a blunt-ended, long, tube-like lymphatic vessel located in the center of each intestinal villus that provides a unique route for drainage of absorbed lipids from the small intestine. However, key regulators for maintaining lacteal integrity are poorly understood. Here, we explore whether and how the gut microbiota regulates lacteal integrity. Germ depletion by antibiotic treatment triggers lacteal regression during adulthood and delays lacteal maturation during the postnatal period. In accordance with compromised lipid absorption, the button-like junction between lymphatic endothelial cells, which is ultrastructurally open to permit free entry of dietary lipids into lacteals, is significantly reduced in lacteals of germ-depleted mice. Lacteal defects are also found in germ-free mice, but conventionalization of germ-free mice leads to normalization of lacteals. Mechanistically, VEGF-C secreted from villus macrophages upon MyD88-dependent recognition of microbes and their products is a main factor in lacteal integrity. Collectively, we conclude that the gut microbiota is a crucial regulator for lacteal integrity by endowing its unique microenvironment and regulating villus macrophages in small intestine.Peer reviewe

S6 kinase 1 plays a key role in mitochondrial morphology and cellular energy flow

Mitochondrial morphology, which is associated with changes in metabolism, cell cycle, cell development and cell death, is tightly regulated by the balance between fusion and fission. In this study, we found that S6 kinase 1 (S6K1) contributes to mitochondrial dynamics, homeostasis and function. Mouse embryo fibroblasts lacking S6K1 (S6K1 KO MEFs) exhibited more fragmented mitochondria and a higher level of Dynamin related protein 1 (Drp1) and active Drp1 (pS616) in both whole cell extracts and mitochondria' fraction. In addition, there was no evidence for autophagy and mitophagy induction in S6K1 depleted cells. Glycolysis and mitochondrial respiratory activity was higher in S6K1-KO MEFs, whereas OxPhos ATP production was not altered. However, inhibition of Drp1 by Mdivi1 (Drp1 inhibitor) resulted in higher OxPhos ATP production and lower mitochondrial membrane potential. Taken together the depletion of S6K1 increased Drpl-mediated fission, leading to the enhancement of glycolysis. The fission form of mitochondria resulted in lower yield for OxPhos ATP production as well as in higher mitochondrial membrane potential. Thus, these results have suggested a potential role of S6K1 in energy metabolism by modulating mitochondrial respiratory capacity and mitochondrial morphology.

Massive Paradoxical Air Embolism in Brain Occurring after Central Venous Catheterization: A Case Report

Cerebral air embolism is a rare but fatal complication of central venous catheterization. Here, we report a case of paradoxical cerebral air embolism associated with central venous catheterization. An 85-yr-old man underwent right internal jugular vein catheterization, and became obtunded. Brain MR imaging and CT revealed acute infarction with multiple air bubbles on the side of catheter insertion. The possibility of cerebral air embolism should be considered in patients developing neurological impairment after central venous catheterization, and efforts should be made to limit cerebral damage

Fatal Biliary-Systemic Air Embolism during Endoscopic Retrograde Cholangiopancreatography: A Case with Multifocal Liver Abscesses and Choledochoduodenostomy

We report a rare case of a massive fatal embolism that occurred in the middle of endoscopic retrograde cholangiopancreatography (ERCP) and retrospectively examine the significant causes of the event. The patient was a 50-year old female with an uncertain history of previous abdominal surgery for multiple biliary stones 20 years prior. The patient presented with acute right upper quadrant pain. An abdominal computed tomographic (CT) scan revealed the presence of multiple stones in the common bile duct (CBD) and intra-hepatic duct (IHD) with biliary obstruction, multifocal liver abscesses, and air-biliarygram. Emergency ERCP showed a wide and straight opening of choledochoduodenostomy, which may have been created during a previous surgery, and multiple filling defects in the CBD. With the use of a forward endoscope, mud stones were extracted through the opening of the choledochoduodenostomy. Cardiac arrest suddenly developed during the procedure, and despite immediate resuscitation, the patient died due to a massive systemic air embolism. We reviewed previously reported fatal cases and accessed factors facilitating air embolisms in this case

Three-Dimensional Human Alveolar Stem Cell Culture Models Reveal Infection Response to SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the cause of a present pandemic, infects human lung alveolar type 2 (hAT2) cells. Characterizing pathogenesis is crucial for developing vaccines and therapeutics. However, the lack of models mirroring the cellular physiology and pathology of hAT2 cells limits the study. Here, we develop a feeder-free, long-term, three-dimensional (3D) culture technique for hAT2 cells derived from primary human lung tissue and investigate infection response to SARS-CoV-2. By imaging-based analysis and single-cell transcriptome profiling, we reveal rapid viral replication and the increased expression of interferon-associated genes and proinflammatory genes in infected hAT2 cells, indicating a robust endogenous innate immune response. Further tracing of viral mutations acquired during transmission identifies full infection of individual cells effectively from a single viral entry. Our study provides deep insights into the pathogenesis of SARS-CoV-2 and the application of defined 3D hAT2 cultures as models for respiratory diseases