Phosphatidylcholine induces apoptosis of 3T3-L1 adipocytes

<p>Abstract</p> <p>Background</p> <p>Phosphatidylcholine (PPC) formulation is used for lipolytic injection, even though its mechanism of action is not well understood.</p> <p>Methods</p> <p>The viability of 3T3-L1 pre-adipocytes and differentiated 3T3-L1 cells was measured after treatment of PPC alone, its vehicle sodium deoxycholate (SD), and a PPC formulation. Western blot analysis was performed to examine PPC-induced signaling pathways.</p> <p>Results</p> <p>PPC, SD, and PPC formulation significantly decreased 3T3-L1 cell viability in a concentration-dependent manner. PPC alone was not cytotoxic to CCD-25Sk human fibroblasts at concentrations <1 mg/ml, whereas SD and PPC formulation were cytotoxic. Western blot analysis demonstrated that PPC alone led to the phosphorylation of the stress signaling proteins, such as p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, and activated caspase-9, -8, -3 as well as cleavage of poly(ADP-ribose) polymerase. However, SD did not activate the apoptotic pathways. Instead, SD and PPC formulation induced cell membrane lysis, which may lead to necrosis of cells.</p> <p>Conclusions</p> <p>PPC results in apoptosis of 3T3-L1 cells.</p

Severe protein C deficiency in a newborn caused by a homozygous pathogenic variant in the PROC gene: a case report

Background Severe protein C deficiency is a rare and inherited cause of thrombophilia in neonates. Protein C acts as an anticoagulant, and its deficiency results in vascular thrombosis. Herein, we report a case of protein C deficiency with a homozygous pathogenic variant in a term neonate, with good outcomes after proper treatment. Case presentation A four-day-old male newborn was transferred to the Seoul National University Hospital on account of dark red to black skin lesions. He was born full-term with an average birth weight without perinatal problems. There were no abnormal findings in the prenatal tests, including intrauterine sonography. The first skin lesion was observed on his right toes and rapidly progressed to proximal areas, such as the lower legs, left arm, and buttock. Under the impression of thromboembolism or vasculitis, we performed a coagulopathy workup, which revealed a high D-dimer level of 23.05 μg/ml. A skin biopsy showed fibrin clots in most capillaries, and his protein C activity level was below 10%, from which we diagnosed protein C deficiency. On postnatal day 6, he experienced an apnea event with desaturation and an abnormal right pupillary light reflex. Brain computed tomography showed multifocal patchy intracranial hemorrhage and intraventricular hemorrhage with an old ischemic lesion. Ophthalmic examination revealed bilateral retinal traction detachments with retinal folds. Protein C concentrate replacement therapy was added to previous treatments including steroids, prostaglandin E1, and anticoagulation. After replacement therapy, there were no new skin lesions, and the previous lesions recovered with scarring. Although there were no new brain hemorrhagic infarctions, there was ongoing ischemic tissue loss, which required further rehabilitation. Ophthalmic surgical interventions were performed to treat the bilateral retinal traction detachments with retinal folds. Molecular analysis revealed a homozygous pathogenic variant in the PROC gene. Conclusion Severe protein C deficiency can manifest as a fatal coagulopathy in any organ. Early diagnosis and proper treatment, including protein C concentrate replacement, may improve outcomes without serious sequelae

The combined clinical impact of red blood cell distribution width and vascular calcification on cardiovascular events and mortality in patients with end-stage kidney disease

Background Little is known about how the interaction between red blood cell distribution width (RDW) and vascular calcification (VC) affects cardiovascular (CV) events and mortality in end-stage kidney disease (ESKD) patients. This study investigated the combined prognostic effect of RDW and VC in ESKD patients starting dialysis. Methods A retrospective single-center study of 582 ESKD patients was conducted. VC was assessed by calculating the aortic calcification index (ACI) using computed tomography. Patients were divided into low ACI-low RDW, low ACI-high RDW, high ACI-low RDW, and high ACI-high RDW groups based on median ACI (17.12) and RDW (14.3) values. The association between RDW and VC and the composite endpoint of CV events and death was analyzed. Results During a median follow-up of 3.1 years (range, 1.5–5.5 years), 165 CV events (28.4%) and 124 deaths (21.4%) occurred. Cox regression showed that the low ACI-high RDW (adjusted hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.04–2.66; p = 0.03) and high ACI-low RDW (adjusted HR, 1.95; 95% CI, 1.21–3.14; p = 0.006) groups had a greater risk of CV events and death than the low ACI-low RDW group. The high ACI-high RDW group had the greatest risk (adjusted HR, 2.23; 95% CI, 1.42–3.52; p = 0.001). The effect of the interaction between ACI and RDW on CV events and mortality was statistically significant (p = 0.005). Conclusion High RDW and VC interact to increase the risk of CV events and death in ESKD patients

Reactive oxygen species and p47phox activation are essential for the Mycobacterium tuberculosis-induced pro-inflammatory response in murine microglia

<p>Abstract</p> <p>Background</p> <p>Activated microglia elicits a robust amount of pro-inflammatory cytokines, which are implicated in the pathogenesis of tuberculosis in the central nervous system (CNS). However, little is known about the intracellular signaling mechanisms governing these inflammatory responses in microglia in response to <it>Mycobacterium tuberculosis </it>(Mtb).</p> <p>Methods</p> <p>Murine microglial BV-2 cells and primary mixed glial cells were stimulated with sonicated Mtb (s-Mtb). Intracellular ROS levels were measured by staining with oxidative fluorescent dyes [2',7'-Dichlorodihydrofluorescein diacetate (H₂DCFDA) and dihydroethidium (DHE)]. NADPH oxidase activities were measured by lucigenin chemiluminescence assay. S-Mtb-induced MAPK activation and pro-inflammatory cytokine release in microglial cells were measured using by Western blot analysis and enzyme-linked immunosorbent assay, respectively.</p> <p>Results</p> <p>We demonstrate that s-Mtb promotes the up-regulation of reactive oxygen species (ROS) and the rapid activation of mitogen-activated protein kinases (MAPKs), including p38 and extracellular signal-regulated kinase (ERK) 1/2, as well as the secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-12p40 in murine microglial BV-2 cells and primary mixed glial cells. Both NADPH oxidase and mitochondrial electron transfer chain subunit I play an indispensable role in s-Mtb-induced MAPK activation and pro-inflammatory cytokine production in BV-2 cells and mixed glial cells. Furthermore, the activation of cytosolic NADPH oxidase p47phox and MAPKs (p38 and ERK1/2) is mutually dependent on s-Mtb-induced inflammatory signaling in murine microglia. Neither TLR2 nor dectin-1 was involved in s-Mtb-induced inflammatory responses in murine microglia.</p> <p>Conclusion</p> <p>These data collectively demonstrate that s-Mtb actively induces the pro-inflammatory response in microglia through NADPH oxidase-dependent ROS generation, although the specific pattern-recognition receptors involved in these responses remain to be identified.</p

ACVR1 Gene Mutation in Sporadic Korean Patients with Fibrodysplasia Ossificans Progressiva

Fibrodysplasia ossificans progressiva (FOP; OMIM 135100) is a rare but extremely disabling genetic disorder of the skeletal system, and is characterized by the progressive development of ectopic ossification of skeletal muscles and subsequent joint ankylosis. The c.617G>A; p.R206H point mutation in the activin A type I receptor (ACVR1) gene has been reported to be a causative mutation of FOP. In the present study, mutation analysis of the ACVR1 gene was performed in 12 patients diagnosed or suspected to have FOP. All patients tested had a de novo heterozygous point mutation of c.617G>A; p.R206H in ACVR1. Mutation analysis confirmed a diagnosis of FOP in patients with ambiguous features, and thus, could be used for diagnostic purposes. Early confirmation through mutation analysis would allow medical professionals to advise on the avoidance of provoking events to delay catastrophic flare-ups of ectopic ossifications

Pneumopericardium as a Complication of Pericardiocentesis

Pneumopericardium is a rare complication of pericardiocentesis, occurring either as a result of direct pleuro-pericardial communication or a leaky drainage system. Air-fluid level surrounding the heart shadow within the pericardium on a chest X-ray is an early observation at diagnosis. This clinical measurement and process is variable, depending on the hemodynamic status of the patient. The development of a cardiac tamponade is a serious complication, necessitating prompt recognition and treatment. We recently observed a case of pneumopericardium after a therapeutic pericardiocentesis in a 20-year-old man with tuberculous pericardial effusion

Development of a Mobile Application, “Wild Flowers of Bukhansan National Park (version 1.0)”, for Identification of Plants in Bukhansan National Park

AbstractWe developed the educational purpose mobile application, named “Wild Flowers of Bukhansan National Park (version 1.0)”, aiming for easy identification of wildflowers for students and visitors in the park. When visitors find a flower or part of plant in the park, visitors can search for its name utilizing the pictures and characters provided in their own smartphone mobile devices or tablet PCs. The application provides pictures of wildflowers in the park and character-based searching system based on 12 diagnostic features (e.g., growth form, leaf arrangement, flower symmetry, petal color, petal number, sepal number, etc). We adopted the complete floristic survey of Chung and Lee (1962) and added species that we confirmed their distribution in the park during the development of this application. In summary, number of vascular plants in this park was estimated to be 428 taxa including 100 families, 280 genera, 327 species, 1 subspecies, 50 varieties, and 5 formas. We provided a total of 588 pictures representing 358 taxa and each taxon includes multiple pictures in many cases. Included identification quizzes can be an efficient educational tool as well as fun activity for students and visitors who are learning plant species in Korea. Our next step will include GPS function in the application for indicating visitor's location and for providing previously reported sites of the species that we interested in the map of the park. The future application which includes GPS function will be a valuable tool for the monitoring of rare plants, plant researches related to the climate changes, etc. We currently provide Korean iPhone version only, and English version and both of android versions will be serviced soon

TmToll-7 Plays a Crucial Role in Innate Immune Responses Against Gram-Negative Bacteria by Regulating 5 AMP Genes in Tenebrio molitor

Although it is known that the Drosophila Toll-7 receptor plays a critical role in antiviral autophagy, its function in other insects has not yet been reported. Here, we have identified a Toll-like receptor 7 gene, TmToll-7, in the coleopteran insect T. molitor and examined its potential role in antibacterial and antifungal immunity. We showed that TmToll-7 expression was significantly induced in larvae 6 h after infection with Escherichia coli and Staphylococcus aureus and 9 h after infection with Candida albicans. However, even though TmToll-7 was induced by all three pathogens, we found that TmToll-7 knockdown significantly reduced larval survival to E. coli, but not to S. aureus, and C. albicans infections. To understand the reasons for this difference, we examined the effects of TmToll-7 knockdown on antimicrobial peptide (AMP) gene expression and found a significant reduction of E. coli-induced expression of AMP genes such as TmTenecin-1, TmDefensin-1, TmDefensin-2, TmColeoptericin-1, and TmAttacin-2. Furthermore, TmToll-7 knockdown larvae infected with E. coli showed significantly higher bacterial growth in the hemolymph compared to control larvae treated with Vermilion dsRNA. Taken together, our results suggest that TmToll-7 plays an important role in regulating the immune response of T. molitor to E. coli