Publications by authors named "Jeong Su Park"

105 Publications

Ginseng Saponin Enriched in Rh1 and Rg2 Ameliorates Nonalcoholic Fatty Liver Disease by Inhibiting Inflammasome Activation.

Nutrients 2021 Mar 5;13(3). Epub 2021 Mar 5.

College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Chungbuk 28160, Korea.

Nonalcoholic fatty liver disease (NAFLD) is becoming one of the most common chronic liver diseases in the world. One of the features of NAFLD is hepatic fat accumulation, which further causes hepatic steatosis, fibrosis, and inflammation. Saponins, the major pharmacologically active ingredients isolated from , contain several ginsenosides, which have various pharmacological and therapeutic functions. However, the ginsenoside-specific molecular mechanism of saponins in NAFLD remains unknown. This study aimed to elucidate the effects of ginseng saponin extract and its ginsenosides on hepatic steatosis, fibrosis, and inflammation and their underlying action mechanism in NAFLD. Mice were fed a fast food diet (FFD) for 16 weeks to induce NAFLD and then treated with saponin extract (50 or 150 mg/kg) for the remaining nine weeks to determine the effects of saponin on NAFLD. Saponin extract administration significantly alleviated FFD-induced hepatic steatosis, fibrosis, and inflammation. Particularly, saponin extract, compared with conventional red ginseng, contained significantly increased amounts of ginsenosides (Rh1 (10.34-fold) and Rg2 (7.1-fold)). In vitro Rh1 and Rg2 treatments exerted an anti-steatotic effect in primary hepatocytes, an antifibrotic effect in hepatic stellate cells, and anti-inflammatory and pro-mitophagy effects in immortalized mouse Kupffer cells. Mechanistically, saponin extract alleviated lipopolysaccharide-induced NLRP3 inflammasome activation by promoting mitophagy. In conclusion, saponin extract inhibited inflammation-mediated pathological inflammasome activation in macrophages, thereby preventing NAFLD development. Thus, saponin extract administration may be an alternative method for NAFLD prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu13030856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999915PMC
March 2021

The Need of Enterococcal Coverage in Severe Intra-Abdominal Infection: Evidence from Animal Study.

J Clin Med 2021 Mar 2;10(5). Epub 2021 Mar 2.

Department of Emergency Medicine, CHA University School of Medicine, Seongnam 13497, Korea.

Intra-abdominal infection (IAI) is a common and important cause of infectious mortality in intensive care units. Adequate source control and appropriate antimicrobial regimens are key in the management of IAI. In community-acquired IAI, guidelines recommend the use of different antimicrobial regimens according to severity. However, the evidence for this is weak. We investigated the effect of enterococcal coverage in antimicrobial regimens in a severe polymicrobial IAI model. We investigated the effects of imipenem/cilastatin (IMP) and ceftriaxone with metronidazole (CTX+M) in a rat model of severe IAI. We observed the survival rate and bacterial clearance rate. We identified the bacteria in blood culture. We measured lactate, alanine aminotransferase (ALT), creatinine, interleukin (IL)-6, IL-10, and reactive oxygen species (ROS) in the blood. Endotoxin tolerance of peripheral blood mononuclear cells (PBMCs) was also estimated to determine the level of immune suppression. In the severe IAI model, IMP improved survival and bacterial clearance compared to CTX+M. Enterococcus spp. were more frequently isolated in the CTX+M group. IMP also decreased plasma lactate, cytokine, and ROS levels. ALT and creatinine levels were lower in IMP group. In the mild-to-moderate IAI model, however, there was no survival difference between the groups. Immune suppression of PBMCs was observed in IAI model, and it was more prominent in the severe IAI model. Compared to CTX+M, IMP improved the outcome of rats in severe IAI model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10051027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958860PMC
March 2021

Cell-permeable transgelin-2 as a potent therapeutic for dendritic cell-based cancer immunotherapy.

J Hematol Oncol 2021 Mar 17;14(1):43. Epub 2021 Mar 17.

School of Life Sciences, Gwangju Institute of Science and Technology (GIST), 123 Cheomdangwagi-ro, Gwangju, 61005, Korea.

Background: Transgelin-2 is a 22 kDa actin-binding protein that has been proposed to act as an oncogenic factor, capable of contributing to tumorigenesis in a wide range of human malignancies. However, little is known whether this tiny protein also plays an important role in immunity, thereby keeping body from the cancer development and metastasis. Here, we investigated the functions of transgelin-2 in dendritic cell (DC) immunity. Further, we investigated whether the non-viral transduction of cell-permeable transgelin-2 peptide potentially enhance DC-based cancer immunotherapy.

Methods: To understand the functions of transgelin-2 in DCs, we utilized bone marrow-derived DCs (BMDCs) purified from transgelin-2 knockout (Tagln2) mice. To observe the dynamic cellular mechanism of transgelin-2, we utilized confocal microscopy and flow cytometry. To monitor DC migration and cognate T-DC interaction in vivo, we used intravital two-photon microscopy. For the solid and metastasis tumor models, OVA B16F10 melanoma were inoculated into the C57BL/6 mice via intravenously (i.v.) and subcutaneously (s.c.), respectively. OTI TCR T cells were used for the adoptive transfer experiments. Cell-permeable, de-ubiquitinated recombinant transgelin-2 was purified from Escherichia coli and applied for DC-based adoptive immunotherapy.

Results: We found that transgelin-2 is remarkably expressed in BMDCs during maturation and lipopolysaccharide activation, suggesting that this protein plays a role in DC-based immunity. Although Tagln2 BMDCs exhibited no changes in maturation, they showed significant defects in their abilities to home to draining lymph nodes (LNs) and prime T cells to produce antigen-specific T cell clones, and these changes were associated with a failure to suppress tumor growth and metastasis of OVA B16F10 melanoma cells in mice. Tagln2 BMDCs had defects in filopodia-like membrane protrusion and podosome formation due to the attenuation of the signals that modulate actin remodeling in vitro and formed short, unstable contacts with cognate CD4 T cells in vivo. Strikingly, non-viral transduction of cell-permeable, de-ubiquitinated recombinant transgelin-2 potentiated DC functions to suppress tumor growth and metastasis.

Conclusion: This work demonstrates that transgelin-2 is an essential protein for both cancer and immunity. Therefore, transgelin-2 can act as a double-edged sword depending on how we apply this protein to cancer therapy. Engineering and clinical application of this protein may unveil a new era in DC-based cancer immunotherapy. Our findings indicate that cell-permeable transgelin-2 have a potential clinical value as a cancer immunotherapy based on DCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13045-021-01058-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968273PMC
March 2021

Potentiating the Antitumor Activity of Cytotoxic T Cells the Transmembrane Domain of IGSF4 That Increases TCR Avidity.

Front Immunol 2020 1;11:591054. Epub 2021 Feb 1.

School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju, South Korea.

A robust T-cell response is an important component of sustained antitumor immunity. In this respect, the avidity of TCR in the antigen-targeting of tumors is crucial for the quality of the T-cell response. This study reports that the transmembrane (TM) domain of immunoglobulin superfamily member 4 (IGSF4) binds to the TM of the CD3 ζ-chain through an interaction between His177 and Asp36, which results in IGSF4-CD3 ζ dimers. IGSF4 also forms homo-dimers through the GxxVA motif in the TM domain, thereby constituting large TCR clusters. Overexpression of IGSF4 lacking the extracellular (IG4ΔEXT) domain potentiates the CD8 T cells to release IFN-γ and TNF-α and to kill OVA-B16F10 melanoma cells. In animal models, IG4ΔEXT significantly reduces B16F10 tumor metastasis as well as tumor growth. Collectively, the results indicate that the TM domain of IGSF4 can regulate TCR avidity, and they further demonstrate that TCR avidity regulation is critical for improving the antitumor activity of cytotoxic T cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2020.591054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882689PMC
February 2021

Impact of a computerised clinical decision support system on vancomycin loading and the risk of nephrotoxicity.

Int J Med Inform 2021 Feb 4;149:104403. Epub 2021 Feb 4.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.

Background: A vancomycin loading dose is recommended for the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections. However, clinicians often do not adhere to these recommendations, mainly due to nephrotoxicity risk, unfamiliarity with the guideline, or complexity of calculating an individual dose. Therefore, we introduced a computerised clinical decision support system (CDSS) for vancomycin loading (hereafter Vancomycin CDSS) to promote the use of vancomycin loading dose.

Methods: We describe a quasi-experimental study spanning 6 months before and 18 months after the deployment of a Vancomycin CDSS. The Vancomycin CDSS was integrated into the hospital's electronic medical record system in the form of a vancomycin order set. Our primary endpoint was the incidence of nephrotoxicity; the secondary endpoint was mean initial vancomycin trough levels. We also conducted a survey to evaluate the reasons why clinicians opted not to utilise a vancomycin loading dose.

Results: After implementation of Vancomycin CDSS, 363 out of 746 patients (49 %) who were first administered vancomycin received a loading dose. We did not find significant differences in nephrotoxicity between the pre- and post-intervention groups, nor between the loading- and non-loading groups. In the pre-intervention group, the mean initial vancomycin trough level was 7.10 mg/L, which was significantly lower than that in the post-intervention group of 11.11 mg/L. In the vancomycin loading group, the mean initial trough level was 11.95 mg/L, compared to 7.55 mg/L in the non-loading group. The main reason stated for not prescribing a vancomycin loading dose was concern about nephrotoxicity.

Conclusion: Introduction of the Vancomycin CDSS did not increase nephrotoxicity and increased the mean initial dose and trough level of vancomycin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijmedinf.2021.104403DOI Listing
February 2021

Whole-Genome Sequencing for Investigating a Health Care-Associated Outbreak of Carbapenem-Resistant .

Diagnostics (Basel) 2021 Jan 29;11(2). Epub 2021 Jan 29.

Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea.

Carbapenem-resistant (CRAB) outbreaks in hospital settings challenge the treatment of patients and infection control. Understanding the relatedness of clinical isolates is important in distinguishing outbreak isolates from sporadic cases. This study investigated 11 CRAB isolates from a hospital outbreak by whole-genome sequencing (WGS), utilizing various bioinformatics tools for outbreak analysis. The results of multilocus sequence typing (MLST), single nucleotide polymorphism (SNP) analysis, and phylogenetic tree analysis by WGS through web-based tools were compared, and repetitive element polymerase chain reaction (rep-PCR) typing was performed. Through the WGS of 11 isolates, three clonal lineages were identified from the outbreak. The coexistence of and with additional aminoglycoside-inactivating enzymes, predicted to confer multidrug resistance, was identified in all isolates. The MLST Oxford scheme identified three types (ST191, ST369, and ST451), and, through whole-genome MLST and whole-genome SNP analyses, different clones were found to exist within the MLST types. wgSNP showed the highest discriminatory power with the lowest similarities among the isolates. Using the various bioinformatics tools for WGS, CRAB outbreak analysis was applicable and identified three discrete clusters differentiating the separate epidemiologic relationships among the isolates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/diagnostics11020201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910894PMC
January 2021

Interplay between Saturated Free Fatty Acids and mmLDL Induces Inflammation in LPS-stimulated Macrophages.

Korean Circ J 2021 Jan 8;51(1):81-82. Epub 2020 Oct 8.

Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4070/kcj.2020.0386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779815PMC
January 2021

Laboratory Diagnostic Methods for Infection: the First Systematic Review and Meta-analysis in Korea.

Ann Lab Med 2021 Mar;41(2):171-180

Department of Laboratory Medicine, Sanggye Paik Hospital, School of Medicine, Inje University, Seoul, Korea.

Background: Various methods are used for the diagnosis of infection (CDI). We systematically analyzed and investigated the performance of current laboratory diagnostic methods for CDI.

Methods: We performed systematic review and meta-analysis of studies in PubMed, Web of Science, Cochrane Library, and KoreaMed. The following methods were evaluated: glutamate dehydrogenase (GDH) enzyme immunoassays (GDH EIAs), toxin A and B detection by enzyme immunoassays (toxin AB EIAs), and nucleic acid amplification tests (NAATs) for toxin genes. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each method were calculated.

Results: Based on 39 studies, the pooled sensitivities/specificities were 92.7%/94.6%, 57.9%/97.0%, and 90.0%/95.8% for GDH EIAs, toxin AB EIAs, and NAATs, respectively, compared with those of toxigenic culture. The pooled sensitivities of automated EIAs were significantly higher than those of non-automated EIAs for both GDH and toxins A and B. The pooled sensitivity of Xpert was significantly higher than those of other NAATs. PPVs increased as CDI prevalence increased, and NPVs were excellent when CDI prevalence was low; at CDI prevalence of 5%, PPV=37%-65% and NPV=97%-100%; at CDI prevalence of 50%, PPV=92%-97% and NPV=65%-98%.

Conclusions: Toxin AB EIAs still show unsatisfactory sensitivity, whereas GDH EIAs and NAATs show relatively high sensitivity. However, toxin AB EIAs are the most specific tests. This study may provide useful information for CDI diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3343/alm.2021.41.2.171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591293PMC
March 2021

Dynamics of viral load and anti-SARS-CoV-2 antibodies in patients with positive RT-PCR results after recovery from COVID-19.

Korean J Intern Med 2021 01 25;36(1):11-14. Epub 2020 Nov 25.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Recently, the number of patients with coronavirus disease 2019 (COVID-19) who have tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), via the reverse transcription polymerase chain reaction (RT-PCR) test, after recovery has increased; this has caused a dilemma regarding the medical measures and policies. We evaluated the dynamics of viral load and anti-SARS-CoV-2 antibodies in four patients with positive RT-PCR results after recovery. In all patients, the highest levels of immunoglobulin G (IgG) and IgM antibodies were reached after about a month of the onset of the initial symptoms. Then, the IgG titers plateaued, and the IgM titers decreased, regardless of RT-PCR results. The IgG and IgM levels did not increase after the post-negative positive RT-PCR results in any of the patients. Our results reinforced that the post-negative positive RT-PCR results may be due to the detection of RNA particles rather than reinfection in individuals who have recovered from COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3904/kjim.2020.325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820639PMC
January 2021

Phosphoinositide 3-kinase inhibitors are effective therapeutic drugs for the treatment of hepatocellular carcinoma?

Clin Mol Hepatol 2020 10 17;26(4):577-578. Epub 2020 Sep 17.

Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3350/cmh.2020.0143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641560PMC
October 2020

Pandemic preparedness of an academic medical centre in the Republic of Korea.

Clin Microbiol Infect 2020 Dec 3;26(12):1595-1599. Epub 2020 Sep 3.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gyeonggi-do, Republic of Korea.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmi.2020.08.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470819PMC
December 2020

Impact of Public Health Interventions on Seasonal Influenza Activity During the SARS-CoV-2 Outbreak in Korea.

Clin Infect Dis 2020 May 30. Epub 2020 May 30.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Seoul National University College of Medicine, Republic of Korea.

Background: COVID-19 was introduced in Korea early and experienced a large outbreak in mid-February. We aimed to review the public health interventions used during the COVID-19 outbreak and describe the impact on seasonal influenza activity in Korea.

Methods: National response strategies and public health interventions, along with daily COVID-19 confirmed cases in Korea were reviewed during the pandemic. National influenza surveillance data were compared between seven sequential seasons. Characteristics of each season, including the rate of influenza-like illness (ILI), duration of epidemic, date of termination of epidemic, distribution of influenza virus strain and hospitalization were analyzed.

Results: After various public health interventions including enforced public education on hand hygiene, cough etiquette and staying at home with respiratory symptoms, universal mask use in public places, refrain from non-essential social activities and school closure, the duration of the influenza epidemic in 2019/2020 decreased by 6-12 weeks and the influenza activity peak rated 49.8 ILI/1,000 visits compared to 71.9-86.2 ILI/1,000 visits of previous seasons. During the period of enforced social distancing from week 9 to 17 of 2020, influenza hospitalization cases were 11.9-26.9-fold lower compared with previous seasons. During the 2019/2020 season, influenza B accounted for only 4%, in contrast with previous seasons in which influenza B accounted for 26.6% to 54.9% of all cases.

Conclusions: Efforts to activate high level national response not only led to a decrease in COVID-19, but also substantial decrease in seasonal influenza activity. Interventions applied to control COVID-19 may serve as useful strategies for prevention and control of influenza in upcoming seasons.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciaa672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314207PMC
May 2020

Fifteen new nucleotide substitutions in variants of human papillomavirus 18 in Korea : Korean HPV18 variants and clinical manifestation.

Virol J 2020 05 24;17(1):70. Epub 2020 May 24.

Department of Laboratory Medicine, Seoul National University Metropolitan Government Boramae Medical Center, Seoul, South Korea.

High-risk human papillomavirus (HPV) infection is an essential factor for the development of cervical cancer. HPV18 is the second most common carcinogenic HPV type following HPV16, but the lineages of HPV18 have been less well studied than those of HPV 16. The purpose of this study was to analyze the nucleotide variants in the E6, E7, and L1 genes of HPV18, to assess the prevalence of HPV18 variants in Korea and to explore the relationship between HPV18 genetic variants and the risk for cervical cancer.A total of 170 DNA samples from HPV18-positive cervical specimens were collected from women admitted to a secondary referral hospital located in Seoul. Among them, the lineages of the 97 samples could be successfully determined by historical nomenclature.All the studied HPV 18 variants were lineage A. Sublineages A1 and A4 comprised 91.7% (89/97) and 1.0% (1/97), respectively. Sublineages other than A1 or A4 comprised 7.2% (7/97). We identified 15 new nucleotide substitutions among 44 nucleotide substitutions: C158T, T317G, T443G, A560G, A5467G, A5560C, A5678C, A6155G, G6462A, T6650G, G6701A, T6809C, A6823G, T6941C and T6953C. Among them, 6 substitutions at positions 317, 443, 5467, 5560, 6462, and 6823 resulted in amino acid changes (E6: F71L and N113K; L1: H13R, H44P, A345T, and N465S, respectively). The pathologic results were classified as normal in 25.8% (25/97) of the women, atypical squamous cells of undermined significance (ASCUS) in 7.2% (7/97), cervical intraepithelial neoplasia (CIN) 1 in 36.1% (35/97), CIN2/3 in 19.6% (18/97), and carcinoma in 12.4% (12/97). There was no significant association between the HPV18 sublineages and the severity of pathologic lesion or the disease progression.This study is the first to analyze the distribution of HPV18 variants in Korean and to associate the results with pathologic findings. Although the HPV18 variants had no significant effect on the degree and progression of the disease, the newly discovered nonsynonymous mutation in L1 might serve as a database to determine vaccine efficacy in Korean women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12985-020-01337-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245819PMC
May 2020

Recommendations Regarding Practical DEL Typing Strategies for Serologically D-Negative Asian Donors.

Transfus Med Hemother 2020 Feb 17;47(1):88-93. Epub 2019 May 17.

Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Republic of Korea.

Background: DEL, the weakest D variant, is mistyped as D-negative by routine serological assays. Transfusion of red blood cells expressing the DEL phenotype has the potential to elicit anti-D alloimmunization in D-negative recipients. The goal of this study was to recommend DEL typing strategies for serologically D-negative Asian donors.

Methods: RhCE phenotyping and the adsorption-elution test were performed on 674 serologically D-negative samples. genotyping using real-time polymerase chain reaction and melting curve analysis were also undertaken to identify DEL alleles. Costs and turnaround time of RhCE phenotyping, the adsorption-elution test, and genotyping were estimated.

Results: Sensitivity and specificity of the adsorption-elution test for serologically D-negative samples were 94.9% (93/98) and 91.5% (527/576), respectively. C+ phenotypes were detected in all 98 samples with DEL alleles. Despite comparable costs, genotyping was more accurate and rapid than the adsorption-elution test.

Conclusions: Two practical DEL typing strategies using RhCE phenotyping as an initial screening method were recommended for serologically D-negative Asian donors. Compared with DEL typing using genotyping, serological DEL typing using adsorption-elution test is predicted to increase the incidence of anti-D alloimmunization and decrease the D-negative donor pool without having any cost-competitiveness but can be used in laboratories where molecular methods are not applicable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000500098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036552PMC
February 2020

Ezetimibe ameliorates lipid accumulation during adipogenesis by regulating the AMPK-mTORC1 pathway.

FASEB J 2020 01 27;34(1):898-911. Epub 2019 Nov 27.

Severance Biomedical Science Institute, Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.

Adipogenesis, a critical process that converts adipocyte precursors into adipocytes, is considered a potential therapeutic target for the treatment of obesity. Ezetimibe, a drug approved by the United States Food and Drug Administration, is used for the treatment of hypercholesterolemia. Recently, it was reported to ameliorate high fat diet-induced dyslipidemia in mice and reduce lipid accumulation in hepatocytes through the activation of AMPK. However, the anti-adipogenic effects of ezetimibe and the underlying molecular mechanism have not yet been elucidated. Here, we found that ezetimibe reduced lipid accumulation via activating AMPK during the early phase of adipogenesis. We also observed that ezetimibe inhibited peroxisome proliferator-activated receptor γ, which is a major transcription factor of adipogenesis. Furthermore, ezetimibe-mediated AMPK activation reduced lipid accumulation by inhibiting mTORC1 signaling, leading to the downregulation of lipogenesis-related genes. Mitotic clonal expansion, required for adipogenesis, accelerates cell cycle progression and cell proliferation. We additionally observed that ezetimibe prevented the progression of mitotic clonal expansion by arresting the cell cycle at the G0/G1 phase, which was followed by the inhibition of cell proliferation. Collectively, ezetimibe-mediated inhibition of adipogenesis is dependent on the AMPK-mTORC1 pathway. Thus, we suggest that ezetimibe might be a promising drug for the treatment of obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1096/fj.201901569RDOI Listing
January 2020

SQSTM1/p62 activates NFE2L2/NRF2 via ULK1-mediated autophagic KEAP1 degradation and protects mouse liver from lipotoxicity.

Autophagy 2020 11 10;16(11):1949-1973. Epub 2020 Jan 10.

Severance Biomedical Science Institute, Yonsei University College of Medicine , Seoul, Republic of Korea.

Lipotoxicity, induced by saturated fatty acid (SFA)-mediated cell death, plays an important role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). The KEAP1 (kelch like ECH associated protein 1)-NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2) pathway is a pivotal defense mechanism against lipotoxicity. We previously reported that SQSTM1/p62 has a cytoprotective role against lipotoxicity through activation of the noncanonical KEAP1- NFE2L2 pathway in hepatocytes. However, the underlying mechanisms and physiological relevance of this pathway have not been clearly defined. Here, we demonstrate that NFE2L2-mediated induction of SQSTM1 activates the noncanonical KEAP1-NFE2L2 pathway under lipotoxic conditions. Furthermore, we identified that SQSTM1 induces ULK1 (unc-51 like autophagy activating kinase 1) phosphorylation by facilitating the interaction between AMPK (AMP-activated protein kinase) and ULK1, leading to macroautophagy/autophagy induction, followed by KEAP1 degradation and NFE2L2 activation. Accordingly, the activity of this SQSTM1-mediated noncanonical KEAP1-NFE2L2 pathway conferred hepatoprotection against lipotoxicity in the livers of conventional - and liver-specific -knockout mice. Moreover, this pathway activity was evident in the livers of patients with nonalcoholic fatty liver. This axis could thus represent a novel target for NAFLD treatment. ACACA: acetyl-CoA carboxylase alpha; ACTB: actin beta; BafA1: bafilomycin A; CM-H2DCFDA:5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate; CQ: chloroquine; CUL3: cullin 3; DMSO: dimethyl sulfoxide; FASN: fatty acid synthase; GSTA1: glutathione S-transferase A1; HA: hemagglutinin; Hepa1c1c7: mouse hepatoma cells; HMOX1/HO-1: heme oxygenase 1; KEAP1: kelch like ECH associated protein 1; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3; MEF: mouse embryonic fibroblast; MTORC1: mechanistic target of rapamycin kinase complex 1; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NAC: N-acetyl-L-cysteine; NAFLD: nonalcoholic fatty liver disease; NASH: nonalcoholic steatohepatitis; NFE2L2/NRF2: nuclear factor, erythroid 2 like 2; NQO1: NAD(P)H quinone dehydrogenase 1; PA: palmitic acid; PARP: poly (ADP-ribose) polymerase 1; PRKAA1/2: protein kinase AMP-activated catalytic subunits alpha1/2; RBX1: ring-box 1; ROS: reactive oxygen species; SESN2: sestrin 2; SFA: saturated fatty acid; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; SREBF1: sterol regulatory element binding transcription factor 1; TBK1: TANK binding kinase 1; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling; ULK1: unc-51 like autophagy activating kinase.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15548627.2020.1712108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595589PMC
November 2020

Fermented Korean Red Ginseng Extract Enriched in Rd and Rg3 Protects against Non-Alcoholic Fatty Liver Disease through Regulation of mTORC1.

Nutrients 2019 Dec 4;11(12). Epub 2019 Dec 4.

College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju 28160, Korea.

The fermentation of Korean red ginseng (RG) increases the bioavailability and efficacy of RG, which has a protective role in various diseases. However, the ginsenoside-specific molecular mechanism of the fermented RG with (CRG) has not been elucidated in non-alcoholic fatty liver disease (NAFLD). A mouse model of NAFLD was induced by a fast-food diet (FFD) and treated with CRG (100 or 300 mg/kg) for the last 8 weeks. CRG-mediated signaling was assessed in the liver cells isolated from mice. CRG administration significantly reduced the FFD-induced steatosis, liver injury, and inflammation, indicating that CRG confers protective effects against NAFLD. Of note, an extract of CRG contains a significantly increased amount of ginsenosides (Rd and Rg3) after bioconversion compared with that of conventional RG. Moreover, in vitro treatment with Rd or Rg3 produced anti-steatotic effects in primary hepatocytes. Mechanistically, CRG protected palmitate-induced activation of mTORC1 and subsequent inhibition of mitophagy and PPARα signaling. Similar to that noted in hepatocytes, CRG exerted anti-inflammatory activity through mTORC1 inhibition-mediated M2 polarization. In conclusion, CRG inhibits lipid-mediated pathologic activation of mTORC1 in hepatocytes and macrophages, which in turn prevents NAFLD development. Thus, the administration of CRG may be an alternative for the prevention of NAFLD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu11122963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949916PMC
December 2019

Cluster of Lymphadenitis due to Nontuberculous Mycobacterium in Children and Adolescents 8-15 Years of Age.

J Korean Med Sci 2019 Dec 2;34(46):e302. Epub 2019 Dec 2.

Department of Pediatrics, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Background: Nontuberculous mycobacteria (NTM) lymphadenitis is an under-recognized entity, and data of the true burden in children are limited. Without a high index of suspicion, diagnosis may be delayed and microbiological detection is challenging. Here, we report a cluster of NTM lymphadenitis experienced in Korean children.

Methods: Subjects under 19 years of age diagnosed with NTM lymphadenitis during November 2016-April 2017 and April 2018 were included. Electronic medical records were reviewed for clinical, laboratory and pathological findings. Information regarding underlying health conditions and environmental exposure factors was obtained through interview and questionnaires.

Results: A total of ten subjects were diagnosed during 18 months. All subjects were 8-15 years of age, previously healthy, male and had unilateral, nontender, cervicofacial lymphadenitis for more than 3 weeks with no significant systemic symptoms and no response to empirical antibiotics. Lymph nodes involved were submandibular (n = 8), preauricular (n = 6) and submental (n = 1). Five patients had two infected nodes and violaceous discoloration was seen in seven subjects. Biopsy specimens revealed chronic granulomatous inflammation and acid-fast bacteria culture identified in two cases and NTM polymerase chain reaction was positive in two cases. Survey revealed various common exposure sources.

Conclusion: NTM lymphadenitis is rare but increasing in detection and it may occur in children and adolescents. Diagnosis requires high index of suspicion and communication between clinicians and the laboratory is essential for identification of NTM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3346/jkms.2019.34.e302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882942PMC
December 2019

Molecular insights into the role of mitochondria in non-alcoholic fatty liver disease.

Arch Pharm Res 2019 Nov 30;42(11):935-946. Epub 2019 Sep 30.

Department of Pharmacy, College of Pharmacy and Medical Research Center, Chungbuk National University, 194-21 Osongsaengmyung-1 Ro, Cheongju, Chungbuk, 28160, South Korea.

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common cause of fatal liver diseases such as cirrhosis, liver cancer, and indications for orthotopic liver transplantation. Given its high prevalence, the absence of FDA-approved drugs for NAFLD is noticeable. In the pathogenesis of NAFLD, it is well known that mitochondrial dysfunction arises as a result of changes in ETC complexes and the membrane potential (Δψm), as well as decreased ATP synthesis. Due to their fundamental role in energy metabolism and cell death decision, alterations in mitochondria are considered to be critical factors causing NAFLD. Reduced levels of β-oxidation, along with increased lipogenesis, result in lipid accumulation in hepatocytes, and the subsequent production of reactive oxygen species and hepatocyte injury, which contribute to hepatic inflammation and fibrosis through the activations of Kupffer cells and hepatic stellate cells. Here, we review the latest findings describing the involvement of mitochondrial processes in the development of NAFLD and discuss the potential targets against which therapeutics for this disease can be developed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12272-019-01178-1DOI Listing
November 2019

A novel strategy for interpreting the T-SPOT.TB test results read by an ELISPOT plate imager.

PLoS One 2019 25;14(9):e0222920. Epub 2019 Sep 25.

Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea.

Background: The T-SPOT.TB can be read by an ELISPOT plate imager as an alternative to a labor-intensive and time-consuming manual reading, but its accuracy has not been sufficiently discussed to date.

Methods: 1,423 test results obtained from manual reading using a microscope and an ELISPOT plate imager were compared. The agreement of qualitative test results was assessed using Cohen's kappa coefficient. The relationship of spot counts was studied using Bland-Altman analysis.

Results: The overall percent agreement of the qualitative test results was 95.43% with a kappa coefficient of 0.91. Positive test results with the maximum net spot count of 8 and borderline test results showed relatively high discordance. The agreement of spot counts in panel A, panel B, and nil control was good, and variability did not increase with higher spot counts. On the basis of study findings, a novel strategy for interpreting the test results by an ELISPOT plate imager was proposed.

Conclusions: To increase diagnostic accuracy, positive test results with the maximum net spot count of 8 and borderline test results should be manually confirmed. Our strategy could be a practical guide for laboratories to build their own strategies for interpreting the test results by an ELISPOT plate imager.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222920PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760805PMC
March 2020

Spatiotemporal Expression of Anticoagulation Factor in Freshwater Leeches.

Int J Mol Sci 2019 Aug 16;20(16). Epub 2019 Aug 16.

School of Biological Sciences, College of Natural Sciences, Chungbuk National University, Cheongju, Chungbuk 28644, Korea.

, which was originally discovered in the salivary glands of the Mexican leech , was newly isolated from . To confirm the temporal expression of during embryogenesis, we carried out semi-quantitative RT-PCR. was uniquely expressed at stage 4 of the cleavage and was strongly expressed in the late stages of organogenesis, as were other members. In order to confirm the spatial expression of , we performed fluorescence in situ hybridization in the late stages of organogenesis. The expression of each in the proboscis showed a similar pattern and varied in expression in the body. In addition, the spatial expression of orthologs in different leeches showed the possibility of different function across leech species. was expressed in the same region as , which is a known mediator of signal transduction pathway. Hau-antistasin1 is probably a downstream target of Hedgehog signaling, involved in segment polarity signal pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms20163994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719055PMC
August 2019

Repositioning of niclosamide ethanolamine (NEN), an anthelmintic drug, for the treatment of lipotoxicity.

Free Radic Biol Med 2019 06 26;137:143-157. Epub 2019 Apr 26.

Severance Biomedical Science Institute, Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. Electronic address:

Nonalcoholic steatohepatitis (NASH) is a common liver disease associated with metabolic disorders, including obesity and type 2 diabetes (T2D). Despite its worldwide prevalence, there are no effective drugs for the treatment of NASH. The progression of NASH is mainly accelerated by reactive oxygen species (ROS)-induced lipotoxicity. The transcription factor known as nuclear factor erythroid 2-related factor 2 (Nrf2) is pivotal for the elimination of ROS. Accordingly, activators of Nrf2 have been implicated as promising therapeutic targets for the treatment of NASH. Niclosamide (ethanolamine salt; NEN), a drug approved by the US Food and Drug Administration (USFDA), is currently used as an anthelmintic drug for the treatment of parasitic infections. Recently, NEN was shown to improve hepatic steatosis in high-fat diet (HFD)-fed mice. However, the underlying mechanism of its antioxidant function in NASH remains unknown. Here, we demonstrate that NEN induces AMPK-mediated phosphorylation of p62 at S351 that can lead to noncanonical Nrf2 activation. We also demonstrate that NEN protects cells and mouse liver from acute lipotoxic stress through activating p62-dependent Keap1-Nrf2 pathway. Taken together, NEN can be used for clinical applications and has the potential to provide a new therapeutic option for NASH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.freeradbiomed.2019.04.030DOI Listing
June 2019

Dual roles of ULK1 (unc-51 like autophagy activating kinase 1) in cytoprotection against lipotoxicity.

Autophagy 2020 01 9;16(1):86-105. Epub 2019 Apr 9.

Severance Biomedical Science Institute, Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.

Saturated fatty acid (SFA)-induced lipotoxicity is caused by the accumulation of reactive oxygen species (ROS), which is associated with damaged mitochondria. Moreover, lipotoxicity is crucial for the progression of nonalcoholic steatohepatitis (NASH). Autophagy is required for the clearance of protein aggregates or damaged mitochondria to maintain cellular metabolic homeostasis. The NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2)-KEAP1 (kelch like ECH associated protein 1) pathway is essential for the elimination of ROS. ULK1 (unc-51 like autophagy activating kinase 1; yeast Atg1) is involved in the initiation of autophagy; however, its role in lipotoxicity-induced cell death in hepatocytes and mouse liver has not been elucidated. We now show that ULK1 potentiates the interaction between KEAP1 and the autophagy adaptor protein SQSTM1/p62, thereby mediating NFE2L2 activation in a manner requiring SQSTM1-dependent autophagic KEAP1 degradation. Furthermore, ULK1 is required for the autophagic removal of damaged mitochondria and to enhance binding between SQSTM1 and PINK1 (PTEN induced kinase 1). This study demonstrates the molecular mechanisms underlying the cytoprotective role of ULK1 against lipotoxicity. Thus, ULK1 could represent a potential therapeutic target for the treatment of NASH.: ACTB: actin beta; CM-HDCFDA:5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate; CQ: chloroquine; CUL3: cullin 3; DMSO: dimethyl sulfoxide; GSTA1: glutathione S-transferase A1; HA: hemagglutinin; Hepa1c1c7: mouse hepatoma cells; HMOX1/HO-1: heme oxygenase 1; KEAP1: kelch like ECH associated protein 1; LPS: lipopolysaccharides; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MAPK8/JNK: mitogen-activated protein kinase 8; MEF: mouse embryonic fibroblast; MFN1: mitofusin 1; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NASH: nonalcoholic steatohepatitis; NFE2L2/NRF2: nuclear factor, erythroid 2 like 2; NQO1: NAD(P)H quinone dehydrogenase 1; PA: palmitic acid; PARP: poly (ADP-ribose) polymerase 1; PINK1: PTEN induced kinase 1; PRKAA1/2: protein kinase AMP-activated catalytic subunits alpha1/2; PRKN/PARK2: parkin RBR E3 ubiquitin protein ligase; PRKC/PKC: protein kinase C; RBX1: ring-box 1; ROS: reactive oxygen species; SFA: saturated fatty acid; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; TOMM20: translocase of outer mitochondrial membrane 20; TUBA: tubulin alpha; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling; ULK1: unc-51 like autophagy activating kinase 1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15548627.2019.1598751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984596PMC
January 2020

Laboratory Diagnosis of Infection in Korea: The First National Survey.

Ann Lab Med 2019 May;39(3):317-321

Department of Laboratory Medicine, Sanggye Paik Hospital, School of Medicine, Inje University, Seoul, Korea.

In May 2015, we conducted a voluntary online survey on laboratory diagnostic assays for infection (CDI) across clinical microbiology laboratories in Korea. Responses were obtained from 66 laboratories, including 61 hospitals and five commercial laboratories. Among them, nine laboratories reported having not conducted CDI assays. The toxin AB enzyme immunoassay (toxin AB EIA), nucleic acid amplification test (NAAT), and culture, alone or in combination with other assays, were used in 51 (89.5%), 37 (64.9%), and 37 (64.9%) of the remaining 57 laboratories, respectively, and 23 (40.4%) of the laboratories performed all three assays. Only one laboratory used the glutamate dehydrogenase assay. Nine laboratories used the toxin AB EIA as a stand-alone assay. The median (range) of examined specimens in one month for the toxin AB EIA, NAAT, and culture was 160 (50-2,060), 70 (7-720), and 130 (9-750), respectively. These findings serve as valuable basic data regarding the current status of laboratory diagnosis of CDI in Korea, offering guidance for improved implementation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3343/alm.2019.39.3.317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340851PMC
May 2019

Microarray-Based Nucleic Acid Assay and MALDI-TOF MS Analysis for the Detection of Gram-Negative Bacteria in Direct Blood Cultures.

Am J Clin Pathol 2019 01;151(2):143-153

Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

Objectives: To compare a microarray-based identification and resistance determination system (blood culture gram-negative [BC-GN]; Nanosphere, Northbrook, IL) with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for direct blood cultures (BCs).

Methods: BC-GN and MALDI-TOF MS assay results from direct BCs were compared with conventional test results after pure culture.

Results: Among 124 BCs, 130 gram-negative rods (GNRs), including six cultures with mixed GNRs (117 bacteria were covered by the BC-GN panel), were detected. The BC-GN test presented 116/117 (99.1%) concordance for the identification of targeted GNRs. Among the six polymicrobial BCs, 10 targeted GNRs were correctly identified. Among the 100 BCs tested by MALDI-TOF MS, 88/106 (86.7%) GNRs were correctly identified, and 18 GNRs were not identified. Among the six polymicrobial samples, seven of 12 GNRs (58.3%) were correctly identified.

Conclusions: The BC-GN assay exhibited superior performance compared with MALDI-TOF MS for the identification of targeted GNRs in direct BCs, particularly in polymicrobial samples.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcp/aqy118DOI Listing
January 2019

Clinical and Molecular Characterization of Panton-Valentine Leukocidin-Positive Invasive Staphylococcus aureus Infections in Korea.

Microb Drug Resist 2019 Apr 31;25(3):450-456. Epub 2018 Oct 31.

1 Department of Internal Medicine, Seoul National University Bundang Hospital , Seongnam, Republic of Korea.

Aim: Panton-Valentine leukocidin (PVL) is a virulent cytotoxin and an indicator of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infection. In this study, we evaluated the prevalence and clinical and molecular characteristics of PVL-positive invasive S. aureus (ISA) infections in Korea.

Results: A collection of 1,962 nonduplicate clinical isolates were screened for multilocus sequence typing, staphylococcal cassette chromosome mec (SCCmec), accessory gene regulator typing, major toxins, and antimicrobial susceptibility. Twenty-eight (1.4%) PVL-positive S. aureus samples were found; of them 19 (67.9%) were MRSA (8 CA and 11 healthcare-associated infections). Seventeen patients (60.7%) were men (median age: 63 years; range: 13-93 years) and 12 patients (42.9%) had no underlying comorbidities. The most common infections were skin and skin structure infection (SSSI) and pneumonia. The 30-day mortality rate was 37.0%. The most common PVL-positive MRSA clones were ST8-SCCmec IVa and ST30-SCCmec IVc along with their single-locus variants. Antimicrobial susceptibility and toxin-gene profile differed according to the clone.

Conclusions: ISA infections caused by PVL-positive strains are rare in Korea, with the two most common infections being SSSI and pneumonia. Our findings indicated that several PVL-positive MRSA clones, predominantly ST8-SCCmecIVa and ST30-SCCmecIVc, were circulating and causing sporadic cases of ISA infections in the community and hospital settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/mdr.2018.0238DOI Listing
April 2019

Pharmacokinetic Characteristics and Limited Sampling Strategies for Therapeutic Drug Monitoring of Colistin in Patients With Multidrug-Resistant Gram-Negative Bacterial Infections.

Ther Drug Monit 2019 02;41(1):102-106

Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam.

Background: Colistin is increasingly used as the last therapeutic option for the treatment of multidrug-resistant, Gram-negative bacterial infections. To ensure safe and efficacious use of colistin, therapeutic drug monitoring (TDM) is needed due to its narrow therapeutic window. This study aimed to evaluate the pharmacokinetic (PK) characteristics of colistin and to guide TDM in colistin-treated patients in Korea.

Methods: In a prospective study, we analyzed PK characteristics in 15 patients who intravenously received colistin methanesulfonate twice per day. Colistin methanesulfonate doses were adjusted based on renal function of the subjects. The appropriate blood sampling points for TDM were evaluated by analyzing the correlations between the PK parameters and the plasma concentrations at each time point.

Results: The mean values for the minimum, maximum, and average concentrations (Cmin, Cmax, and Caverage) of colistin at steady state were 2.29, 5.5, and 3.38 mg/L, respectively. The dose-normalized Cmin, Cmax, Caverage, and area under the plasma concentration-time curve from 0 to the last measurable concentration (AUClast) showed negative correlations with the creatinine clearance. The combination of the 0- and 2-hour post-dose plasma concentrations was evaluated as the appropriate sampling point for TDM. Two patients reported nephrotoxic adverse events during colistin administration.

Conclusions: Our study clarifies the PK characteristics of successful colistin treatment using TDM. Further evaluations in a larger patient population are needed to confirm the clinical usefulness of colistin TDM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/FTD.0000000000000572DOI Listing
February 2019

The Antidiabetic Drug Lobeglitazone Protects Mice From Lipogenesis-Induced Liver Injury via Mechanistic Target of Rapamycin Complex 1 Inhibition.

Front Endocrinol (Lausanne) 2018 21;9:539. Epub 2018 Sep 21.

Severance Biomedical Science Institute, Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul, South Korea.

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder closely linked with type II diabetes (T2D). The progression of NAFLD is associated with the induction of lipogenesis through hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) pathway. An increase in lipogenesis induces endoplasmic reticulum (ER) stress and accelerates oxidative liver injury in the pathogenesis of NAFLD. Lobeglitazone, one of thiazolidinediones (TZDs), is used as an antidiabetic drug to lower serum glucose level through an increase in insulin sensitivity. It is known to improve pathological symptoms in animals and humans with NAFLD. However, the underlying molecular mechanism of the protective effects of lobeglitazone against NAFLD has not been elucidated. Here, we show that under the physiological condition of acute lipogenesis, lobeglitazone inhibits hepatic lipid synthesis, the subsequent ER stress, and ω-oxidation of fatty acids by inhibiting the mTORC1 pathway. As a result, lobeglitazone protected mice from lipogenesis-induced oxidative liver injury. Taken together, lobeglitazone might be a suitable drug for the treatment of patients with diabetes and NAFLD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2018.00539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161559PMC
September 2018

Statues and Improvement of Electronic Medical Record System in Traditional Korean Medicine.

J Pharmacopuncture 2018 Sep 30;21(3):195-202. Epub 2018 Sep 30.

Department of Obstetrics and Gynecology, College of Korean Medicine, Sangji University, Korea.

Objectives: The study was to survey use of electronic medical records in subjects of Korean medicine doctors working for Korean medicine organizations and to contemplate ways to develop utilization of electronic medical records.

Methods: On August 2017, it conducted online self-reported survey on subjects of Korean medicine doctors at Korean hospitals and clinics who agreed to participate in the study. A total 40 doctors in hospital and 279 doctors in clinic were included. The surveyed contents include kinds of electronic chart, reason for not using electronic medical records and problems with creation of medical records.

Results: It finds that 100% of those working at Korean medicine hospitals and 86.4% of those at Korean medicine clinics have used electronic medical records. Subjects answered the biggest reason for not using electronic medical records was inconvenience. The most serious problems with creation of electronic medical records at Korean medicine organizations found in the study include there was no method of creation of medical records and no standardized terminology for use in electronic medical records.

Conclusion: For utilization of electronic medical records at Korean medicine organizations, standardization of terminology, development of EMR in favour of its users and development of strategy that motivates use of EMR are required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3831/KPI.2018.21.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168188PMC
September 2018

T cell microvilli constitute immunological synaptosomes that carry messages to antigen-presenting cells.

Nat Commun 2018 09 7;9(1):3630. Epub 2018 Sep 7.

School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju, 61005, Korea.

Microvilli on T cells have been proposed to survey surfaces of antigen-presenting cells (APC) or facilitate adhesion under flow; however, whether they serve essential functions during T cell activation remains unclear. Here we show that antigen-specific T cells deposit membrane particles derived from microvilli onto the surface of cognate antigen-bearing APCs. Microvilli carry T cell receptors (TCR) at all stages of T cell activation and are released as large TCR-enriched, T cell microvilli particles (TMP) in a process of trogocytosis. These microvilli exclusively contain protein arrestin-domain-containing protein 1, which is directly involved in membrane budding and, in combination with vacuolar protein-sorting-associated protein 4, transforms large TMPs into smaller, exosome-sized TMPs. Notably, TMPs from CD4 T cells are enriched with LFA-2/CD2 and various cytokines involved in activating dendritic cells. Collectively, these results demonstrate that T cell microvilli constitute "immunological synaptosomes" that carry T cell messages to APCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-018-06090-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128830PMC
September 2018