Publications by authors named "Ji Hyun Park"

351 Publications

De Ritis ratio as a predictor of 1-year mortality after burn surgery.

Burns 2021 Feb 17. Epub 2021 Feb 17.

Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address:

Background: Burn is an overwhelming injury. The De Ritis ratio, defined as aspartate aminotransferase to alanine aminotransferase ratio, can be used to predict poor outcomes. We evaluated the risk factors, including the De Ritis ratio, associated with 1-year mortality after burn surgery.

Methods: Patients who underwent burn surgery from 2009 to 2019 were retrospectively evaluated. Multivariate Cox regression analysis was conducted to evaluate the risk factors for 1-year mortality after burn surgery. Receiver operating characteristic (ROC) curve analysis of the De Ritis ratio was performed to predict postoperative 1-year mortality. Kaplan-Meier survival analysis was also conducted. Other postoperative outcomes, such as durations of hospital and intensive care unit stays, acute kidney injury, and major adverse cardiac events, were evaluated.

Results: One-year mortality after burn surgery occurred in 247 (19.9%) of 1244 patients. The risk factors for 1-year mortality after burn surgery were the De Ritis ratio, age, American Society of Anesthesiologists physical status, diabetes mellitus, total body surface area burned, inhalation injury, serum creatinine level, and serum albumin level. The area under the ROC curve for the De Ritis ratio was 0.716 (optimal cutoff=1.9). The 1-year mortality rate after burn surgery was significantly higher in patients with a De Ritis ratio >1.9 than in those with a De Ritis ratio ≤1.9 (35.8% vs. 11.8%, P<0.001). The survival rate was significantly higher in patients with a De Ritis ratio ≤1.9 than in those with a De Ritis ratio >1.9 (log-rank test, P<0.001). Intensive care unit stay, acute kidney injury, and major adverse cardiac events were significantly higher in patients with a De Ritis ratio >1.9 than in those with a De Ritis ratio ≤1.9 (P=0.006, P<0.001, and P<0.001, respectively).

Conclusions: The preoperative De Ritis ratio was a risk factor for 1-year mortality after burn surgery. The De Ritis ratio >1.9 was significantly associated with an increased 1-year mortality after burn surgery. These findings emphasized the importance of identifying burn patients with an increased De Ritis ratio to reduce the mortality after burn surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.burns.2021.02.001DOI Listing
February 2021

Combination of three-dimensional placental vascular indices and volume and uterine artery pulsatility index at 10-13 weeks of gestation could improve the prediction of adverse pregnancy outcomes.

J Obstet Gynaecol Res 2021 Apr 5. Epub 2021 Apr 5.

Department of Obstetrics and Gynecology, The Catholic University of Korea, Seoul, South Korea.

Aim: To evaluate whether three-dimensional (3D) placental vascular indices and volumes during the first trimester of pregnancy can be used as predictors of subsequent adverse outcomes.

Methods: This was a prospective cohort study including women with singleton pregnancies between 10 and 13 weeks. 3D placental volume and vascular indices and uterine artery pulsatility index (UtA-PI) were measured. Adverse outcomes were defined whether there was any of the following complications: small for gestational age pregnancy, preterm delivery, and preeclampsia. The serum pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (β-hCG) levels were also compared. We analyzed the screening performances of these parameters for prediction of any of adverse outcomes.

Results: Of 348 women screened, 300 women were completed follow-up. Overall, 57 (19.0%) of 300 women developed any of adverse pregnancy outcomes. Multiple logistic regression analysis demonstrated that gestational age-adjusted z-scores of log placental volume (odds ratio [OR], 0.572; 95% confidence interval [CI], 0.416-0.788), log placental vascularization flow index (VFI; OR, 0.676; 95% CI, 0.496-0.921), and log UtA-PI (OR, 1.910; 95% CI, 1.335-2.731) were significantly associated adverse pregnancy outcomes. The multivariate model combining placental VFI, placental volume, UtA-PI, and underweight or obese body mass index exhibited the highest screening performances (AUC = 0.77) and PAPP-A and β-hCG did not add any significance to multivariate model.

Conclusions: Placental volume and vascular indices at 10-13 weeks of gestation are significantly associated with adverse pregnancy outcomes. Combination of these placental indices and UtA-PI could improve the screening performance for adverse outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jog.14781DOI Listing
April 2021

Correction to: Aberrant Expression of Sodium-Potassium-Chloride Cotransporter in Endometriosis.

Reprod Sci 2021 Mar 24. Epub 2021 Mar 24.

Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s43032-021-00551-0DOI Listing
March 2021

STK3/STK4 signalling in adipocytes regulates mitophagy and energy expenditure.

Nat Metab 2021 03 23;3(3):428-441. Epub 2021 Mar 23.

College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.

Obesity reduces adipocyte mitochondrial function, and expanding adipocyte oxidative capacity is an emerging strategy to improve systemic metabolism. Here, we report that serine/threonine-protein kinase 3 (STK3) and STK4 are key physiological suppressors of mitochondrial capacity in brown, beige and white adipose tissues. Levels of STK3 and STK4, kinases in the Hippo signalling pathway, are greater in white than brown adipose tissues, and levels in brown adipose tissue are suppressed by cold exposure and greatly elevated by surgical denervation. Genetic inactivation of Stk3 and Stk4 increases mitochondrial mass and function, stabilizes uncoupling protein 1 in beige adipose tissue and confers resistance to metabolic dysfunction induced by high-fat diet feeding. Mechanistically, STK3 and STK4 increase adipocyte mitophagy in part by regulating the phosphorylation and dimerization status of the mitophagy receptor BNIP3. STK3 and STK4 expression levels are elevated in human obesity, and pharmacological inhibition improves metabolic profiles in a mouse model of obesity, suggesting STK3 and STK4 as potential targets for treating obesity-related diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s42255-021-00362-2DOI Listing
March 2021

Bio-specific immobilization of enzymes on electrospun PHB nanofibers.

Enzyme Microb Technol 2021 Apr 28;145:109749. Epub 2021 Jan 28.

Department of Chemical Engineering and Applied Chemistry, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Republic of Korea. Electronic address:

Enzyme immobilization provides substantial advantages in terms of improving the efficiency of enzymatic process as well as enhancing the reusability of enzymes. Phasins (PhaPs) are naturally occurring polyhydroxyalkanoate (PHA)-binding proteins, and thus can potentially be used as a fusion partner for oriented immobilization of enzymes onto PHA supports. However, presently available granular PHA supports have low surface-area-to-volume ratio and limited configurational flexibility of enzymatic reactions. In this study, we explored the use of electrospun polyhydroxybutyrate (PHB) nanofibers as an alternative support for high density immobilization of a PhaP-fused lipase. As envisioned, the electrospun PHB nanofibers could anchor 120-fold more enzyme than PHB granules of the same weight. Furthermore, the enzymes immobilized onto the PHB nanofibers exhibited markedly higher stability and activity compared to when immobilized on conventional immobilization supports. Our approach combines the advantageous features of nanofibrous material and specificity of biomolecular interaction for the efficient use of enzymes, which can be widely adopted in the development of various enzymatic processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.enzmictec.2021.109749DOI Listing
April 2021

Extracellular Mitochondria Signals in CNS Disorders.

Front Cell Dev Biol 2021 5;9:642853. Epub 2021 Mar 5.

Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States.

Mitochondria actively participate in the regulation of cell respiratory mechanisms, metabolic processes, and energy homeostasis in the central nervous system (CNS). Because of the requirement of high energy, neuronal functionality and viability are largely dependent on mitochondrial functionality. In the context of CNS disorders, disruptions of metabolic homeostasis caused by mitochondrial dysfunction lead to neuronal cell death and neuroinflammation. Therefore, restoring mitochondrial function becomes a primary therapeutic target. Recently, accumulating evidence suggests that active mitochondria are secreted into the extracellular fluid and potentially act as non-cell-autonomous signals in CNS pathophysiology. In this mini-review, we overview findings that implicate the presence of cell-free extracellular mitochondria and the critical role of intercellular mitochondrial transfer in various rodent models of CNS disorders. We also discuss isolated mitochondrial allograft as a novel therapeutic intervention for CNS disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.642853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973090PMC
March 2021

Aberrant Expression of Sodium-Potassium-Chloride Cotransporter in Endometriosis.

Reprod Sci 2021 Mar 11. Epub 2021 Mar 11.

Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.

Cell membrane ion channels have important roles in cell migration during cancer development and metastasis. Although endometriosis is a benign gynecological disease, some migration and invasion characteristics of endometriosis are similar to those of cancer. However, only a few studies have examined cell membrane ion channels and their associations with endometriosis. This study aimed to investigate the effects of these ion channels on development of endometriosis. A total of 39 women who underwent laparoscopic ovarian cyst enucleation were included in the study population. Eutopic endometrium or ectopic endometrium tissues were obtained from each patient based on allocation to an endometriosis group (n=21) or a control group (n=18). Quantitative real-time PCR (qRT-PCR) and western blot analyses were performed to quantify NKCC1, NKCC2, and CLCN3 mRNA expression and protein concentrations. SiRNA transfection and migration assays of the endometrial stromal cells were performed to test the effects of the ion channels on the migration ability. The qRT-PCR and western blot analyses revealed significantly elevated mRNA expression and protein expression of NKCC1, NKCC2, and CLCN3 in the ectopic endometrial tissue from the patients with endometriosis (p < 0.05). Migration assay of siRNA transfected cells suggested a decreased migratory potential of the endometrial stromal cells (p < 0.001). The magnitudes of expression of NKCC1, NKCC2, and CLCN3 were positively correlated with endometrioma size. The increased expression of NKCC1, NKCC2, and CLCN3 in endometriosis offers opportunities to understand mechanisms of endometriosis and develop novel therapeutic approaches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s43032-021-00531-4DOI Listing
March 2021

The prognostic nutritional index on postoperative day one is associated with one-year mortality after burn surgery in elderly patients.

Burns Trauma 2021 Jan 1;9:tkaa043. Epub 2021 Mar 1.

Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea.

Background: Burn injury in elderly patients can result in poor outcomes. Prognostic nutritional index (PNI) can predict the perioperative nutritional status and postoperative outcomes. We aim to evaluate the risk factors, including PNI, for one-year mortality after burn surgery in elderly patients.

Methods: Burn patients aged ≥65 years were retrospectively included. PNI was calculated using the following equation: 10 × serum albumin level (g/dL) + 0.005 × total lymphocyte count (per mm). Cox regression, receiver operating characteristic curve and Kaplan-Meier survival analyses were performed to evaluate the risk factors for postoperative one-year mortality.

Results: Postoperative one-year mortality occurred in 71 (37.6%) of the 189 elderly burn patients. Risk factors for one-year mortality were PNI on postoperative day one (hazard ratio (HR) = 0.872; 95% CI = 0.812-0.936;  < 0.001), Sequential Organ Failure Assessment score (HR = 1.112; 95% CI = 1.005-1.230;  = 0.040), American Society of Anesthesiologists physical status (HR = 2.064; 95% CI = 1.211-3.517;  = 0.008), total body surface area burned (HR = 1.017; 95% CI = 1.003-1.032;  = 0.015) and preoperative serum creatinine level (HR = 1.386; 95% CI = 1.058-1.816;  = 0.018). The area under the curve of PNI for predicting one-year mortality after burn surgery was 0.774 (optimal cut-off value = 25.5). Patients with PNI ≤25.5 had a significantly lower one-year survival rate than those with PNI >25.5 (32.1% 75.9%,  < 0.001).

Conclusions: PNI on postoperative day one was associated with postoperative one-year mortality in elderly burn patients. The postoperative one-year survival rate was lower in patients with PNI ≤25.5 than in those with PNI >25.5. These findings indicate the importance of identifying elderly burn patients with low PNI, thereby reducing the mortality after burn surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/burnst/tkaa043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935376PMC
January 2021

Exendin-4, a glucagon-like peptide receptor agonist, facilitates osteoblast differentiation via connexin43.

Endocrine 2021 Feb 27. Epub 2021 Feb 27.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Jeonbuk National University Medical School, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea.

Purpose: To investigate whether exendin-4 (Ex-4), a glucagon-like peptide 1 receptor (GLP-1R) agonist, affects connexin 43 (Cx43) expression in osteoblasts, and determine the specific mechanism underlying Cx43 modulation by Ex-4.

Methods: Osteoblast-like MC3T3-E1 cells were treated with Ex-4 with or without GLP-1R antagonist. We assessed Cx43 expression using RT-PCR, western blotting, and confocal microscopy; visualized intercellular communication using Lucifer yellow dye transfer assay; evaluated osteoblast differentiation using alkaline phosphatase and Alizarin red S (ARS) staining. Cx43 silencing or overexpression was investigated via RNA-interference or adenovirus infection. The mechanism underlying Cx43 regulation by Ex-4 was determined via treatment with either Src kinase inhibitor, KX2-391, Akt activator, sc79, or inhibitor, LY294002.

Results: Ex-4 treatment enhanced Cx43 expression and gap junctional intercellular communication in MC3T3-E1 cells. GLP-1R antagonist pretreatment abrogated the induction of Cx43 expression. Cx43 silencing significantly decreased ARS staining intensity in Ex-4-treated cells, whereas overexpression enhanced cell differentiation. Treatment with KX2-391 reduced both the Ex-4-induced increase of Cx43 expression and p-Akt protein levels. sc79 upregulated Cx43 expression, while LY294002 attenuated Cx43 upregulation by Ex-4.

Conclusions: Induced Cx43 expression in osteoblasts via the Src-Akt signaling pathway illustrates the underlying mechanism for promoting osteoblast differentiation by Ex-4.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12020-021-02664-7DOI Listing
February 2021

Changes in Gastric Corpus Microbiota With Age and After Eradication: A Long-Term Follow-Up Study.

Front Microbiol 2020 9;11:621879. Epub 2021 Feb 9.

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

infection changes gastric microbiota profiles. However, it is not clear whether eradication can restore the healthy gastric microbiota. Moreover, there has been no study regarding the changes in gastric microbiota with aging. The objective of this study was to investigate the changes in gastric corpus microbiota with age and following eradication. Changes in corpus mucosa-associated microbiota were evaluated in 43 individuals with endoscopic follow-up > 1 year, including 8 -uninfected and 15 -infected subjects with no atrophy/metaplasia by histology and pepsinogen I/II ratio > 4.0; 17 -infected subjects with atrophy/metaplasia and pepsinogen I/II ratio < 2.5; and 3 subjects with atrophy/metaplasia, no evidence of active infection, negative for anti- immunoglobulin G (IgG) antibody testing, and no previous history of eradication. Successful eradication was achieved in 21 patients. The gastric microbiota was characterized using an Illumina MiSeq platform targeting 16S ribosomal DNA (rDNA). The mean follow-up duration was 57.4 months (range, 12-145 months), and median follow-up visit was 1 (range, 1-3). Relative abundance of Lactobacillales and was increased with atrophy/metaplasia. In -uninfected subjects ( = 8), an increase in Proteobacteria (, Comamonadaceae, ); a decrease in Firmicutes (, ), Fusobacteria (), Nocardioidaceae, , and Prevotella; and a decrease in microbial diversity were observed during the follow-up ( trend < 0.05). In 10 of 21 subjects (47.6%), eradication induced restoration of microbial diversity; however, a predominance of with a decrease in microbial diversity occurred in 11 subjects (52.3%). The presence of atrophy/metaplasia at baseline and higher neutrophil infiltration in the corpus were associated with the restoration of gastric microbiota after successful eradication, whereas a higher relative abundance of at baseline was associated with the predominance of after eradication ( < 0.05). To conclude, in uninfected stomach, relative abundance of Proteobacteria increases, relative abundance of Firmicutes and Fusobacteria decreases, and microbial diversity decreases with aging. eradication does not always restore gastric microbiota; in some individuals, gastric colonization by species occurs after anti- treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2020.621879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900007PMC
February 2021

Late Mortality Prediction of Neutrophil-to-lymphocyte and Platelet Ratio in Patients With Trauma Who Underwent Emergency Surgery: A Retrospective Study.

J Surg Res 2021 Feb 11. Epub 2021 Feb 11.

Department of Anesthesiology and Pain Medicine, Ajou University School of Medicine, Suwon, South Korea. Electronic address:

Background: We aimed to evaluate the usefulness of neutrophil-to-lymphocyte (N/L) and neutrophil-to-lymphocyte platelet (N/LP) ratios in predicting late mortality of patients with trauma who underwent emergency surgery.

Materials And Methods: We retrospectively evaluated patients with trauma older than 19 y who underwent emergency surgery at our level I trauma center. Blood count-based ratios (N/L and N/LP at days 1, 3, and 7 of hospitalization) and trauma scores were analyzed. Statistical analysis was performed using univariable logistic regression and receiver operating curves.

Results: A total of 209 patients were evaluated. N/LP at day 7, N/L at day 7, Trauma Injury Severity Score, Revised Trauma Score, and Injury Severity Score were significantly associated with late mortality. Area under the receiver operating characteristic curves for predicting mortality was highest for N/LP at day 7 (0.867 [95% confidence interval 0.798-0.936], P < 0.001). The group with N/LP greater than the cutoff value (9.3, sensitivity 77.3%, specificity 83.1%) at day 7 showed higher mortality than the group with N/LP less than the cutoff value (35.4% versus 3.2%, P < 0.001, respectively) at day 7.

Conclusions: N/LP at day 7 may be a superior predictor of late mortality compared with preexisting trauma scores in patients with major trauma undergoing emergency surgery, by better reflecting the systemic inflammation status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jss.2020.11.088DOI Listing
February 2021

Transcriptomic Analyses of MYCN-Regulated Genes in Anaplastic Wilms' Tumour Cell Lines Reveals Oncogenic Pathways and Potential Therapeutic Vulnerabilities.

Cancers (Basel) 2021 Feb 6;13(4). Epub 2021 Feb 6.

Cancer Epigenetics Laboratory, School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.

The proto-oncogene is deregulated in many cancers, most notably in neuroblastoma, where gene amplification identifies a clinical subset with very poor prognosis. Gene expression and DNA analyses have also demonstrated overexpression of mRNA, as well as focal amplifications, copy number gains and presumptive change of function mutations of in Wilms' tumours with poorer outcomes, including tumours with diffuse anaplasia. Surprisingly, however, the expression and functions of the MYCN protein in Wilms' tumours still remain obscure. In this study, we assessed MYCN protein expression in primary Wilms' tumours using immunohistochemistry of tissue microarrays. We found MYCN protein to be expressed in tumour blastemal cells, and absent in stromal and epithelial components. For functional studies, we used two anaplastic Wilms' tumour cell-lines, WiT49 and 17.94, to study the biological and transcriptomic effects of MYCN depletion. We found that MYCN knockdown consistently led to growth suppression but not cell death. RNA sequencing identified 561 MYCN-regulated genes shared by WiT49 and 17.94 cell-lines. As expected, numerous cellular processes were downstream of MYCN. MYCN positively regulated the miRNA regulator and known Wilms' tumour oncogene , the genes encoding methylosome proteins PRMT1, PRMT5 and WDR77, and the mitochondrial translocase genes and . MYCN repressed genes including the developmental signalling receptor and the stromal marker . Importantly, we found that MYCN also repressed the presumptive Wilms' tumour suppressor gene , with MYCN knockdown resulting in increased REST protein and concomitant repression of RE1-Silencing Transcription factor (REST) target genes. Together, our study identifies regulatory axes that interact with MYCN, providing novel pathways for potential targeted therapeutics for poor-prognosis Wilms' tumour.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13040656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915280PMC
February 2021

Regulatory roles of G-protein coupled receptors in adipose tissue metabolism and their therapeutic potential.

Arch Pharm Res 2021 Feb 7;44(2):133-145. Epub 2021 Feb 7.

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University; Bio-MAX Institute, Seoul National University, 29-Room # 311, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.

The high incidence of obesity has increased the need to discover new therapeutic targets to combat obesity and obesity-related metabolic diseases. Obesity is defined as an abnormal accumulation of adipose tissue, which is one of the major metabolic organs that regulate energy homeostasis. However, there are currently no approved anti-obesity therapeutics that directly target adipose tissue metabolism. With recent advances in the understanding of adipose tissue biology, molecular mechanisms involved in brown adipose tissue expansion and metabolic activation have been investigated as potential therapeutic targets to increase energy expenditure. This review focuses on G-protein coupled receptors (GPCRs) as they are the most successful class of druggable targets in human diseases and have an important role in regulating adipose tissue metabolism. We summarize recent findings on the major GPCR classes that regulate thermogenesis and mitochondrial metabolism in adipose tissue. Improved understanding of GPCR signaling pathways that regulate these processes could facilitate the development of novel pharmacological approaches to treat obesity and related metabolic disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12272-021-01314-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907040PMC
February 2021

Intraductal papillary mucinous neoplasm of the biliary tract with cardiac metastasis: A case report.

Medicine (Baltimore) 2021 Jan;100(3):e24310

Pancreatobiliary Cancer Clinic, Department of Surgery.

Introduction: Intraductal papillary mucinous neoplasm of the biliary tract (IPNB) is a rare, low-grade neoplasm limited to the bile duct mucosa. The malignant transformation rate is low, and there have been limited reports of metastasis to other organs. Herein, we presented a rare case of a patient who was diagnosed with IPNB concurrent with invasive adenocarcinoma after surgery and was diagnosed with cardiac metastasis 6 months later.

Patient Concerns: A 61-year-old male patient presented with abdominal pain to a local clinic. He was diagnosed with intrahepatic cholangiocarcinoma with pancreatitis and transferred to our hospital.

Diagnosis: Diagnostic testing (magnetic resonance imaging, endoscopic retrograde cholangiopancreatography, positron emission tomography-computed tomography) revealed a papillary neoplasm and invasive adenocarcinoma with papillary neoplasm in the periampullary lesion.

Interventions: Pancreaticoduodenectomy, right hemihepatectomy, and left lateral sectionectomy of the liver were performed. After surgery, we planned gemcitabine-based adjuvant chemotherapy.

Outcomes: Upon completion of the sixth gemcitabine chemotherapy cycle, a hyperechoic, oval-shaped mass (1.3 × 2.6 cm) was found on the outer wall of the right atrium. Resection of a cardiac tumor in the right atrium and patch repair were performed.

Conclusion: To our knowledge, no other case of cardiac metastasis found during observation after surgery for an IPNB has been described. IPNBs are known to be less aggressive and to have a lower metastasis rate than intraductal papillary mucinous neoplasms; therefore, the number of case reports describing metastasis after surgery is relatively low. Our case suggests that close observation is necessary in patients diagnosed with an IPNB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000024310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837973PMC
January 2021

Real-world outcomes of anti-PD1 antibodies in platinum-refractory, PD-L1-positive recurrent and/or metastatic non-small cell lung cancer, and its potential practical predictors: first report from Korean Cancer Study Group LU19-05.

J Cancer Res Clin Oncol 2021 Feb 1. Epub 2021 Feb 1.

Department of Medical Oncology, Seoul St. Mary's Hospital, The Catholic University, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.

Purpose: Although immune-checkpoint inhibitors have become a new therapeutic option for recurrent/metastatic non-small cell lung cancers (R/M-NSCLC), its clinical benefit in the real-world is still unclear.

Methods: We investigated 1181 Korean patients with programmed death-1 ligand 1 (PD-L1)-positive [tumor proportion score (TPS) ≥ 10% by the SP263 assay or ≥ 50% by the 22C3 assay] R/M-NSCLC treated with pembrolizumab or nivolumab after failure of platinum-based chemotherapy.

Results: The median age was 67 years, 13% of patients had ECOG-PS ≥ 2, and 27% were never-smokers. Adenocarcinoma was predominant (61%) and 18.1% harbored an EGFR activating mutation or ALK rearrangement. Pembrolizumab and nivolumab were administered to 51.3% and 48.7, respectively, and 42% received them beyond the third-line chemotherapy. Objective response rate (ORR) was 28.6%. Pembrolizumab group showed numerically higher ORR (30.7%) than the nivolumab group (26.4%), but it was comparable with that of the nivolumab group having PD-L1 TPS ≥ 50% (32.4%). Median progression-free survival (PFS) and overall survival (OS) were 2.9 (95% CI 0-27.9) and 10.7 months (95% CI 0-28.2), respectively. In multivariable analysis, concordance of TPS ≥ 50% in both PD-L1 assays and the development of immune-related adverse events (irAEs) were two significant predictors of better ORR, PFS, and OS. EGFR mutation could also predict significantly worse OS outcomes.

Conclusion: The real-world benefit of later-line anti-PD1 antibodies was comparable to clinical trials in patients with R/M-NSCLC, although patients generally were more heavily pretreated and had poorer ECOG-PS. Concordantly high PD-L1 TPS ≥ 50% and development of irAE could independently predict better treatment outcomes, while EGFR mutation negatively affected OS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00432-021-03527-4DOI Listing
February 2021

Roles of A-kinase Anchor Protein 12 in Astrocyte and Oligodendrocyte Precursor Cell in Postnatal Corpus Callosum.

Stem Cell Rev Rep 2021 Jan 25. Epub 2021 Jan 25.

Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.

The formation of the corpus callosum in the postnatal period is crucial for normal neurological function, and clinical genetic studies have identified an association of 6q24-25 microdeletion in this process. However, the mechanisms underlying corpus callosum formation and its critical gene(s) are not fully understood or identified. In this study, we examined the roles of AKAP12 in postnatal corpus callosum formation by focusing on the development of glial cells, because AKAP12 is coded on 6q25.1 and has recently been shown to play roles in the regulations of glial function. In mice, the levels of AKAP12 expression was confirmed to be larger in the corpus callosum compared to the cortex, and AKAP12 levels decreased with age both in the corpus callosum and cortex regions. In addition, astrocytes expressed AKAP12 in the corpus callosum after birth, but oligodendrocyte precursor cells (OPCs), another major type of glial cell in the developing corpus callosum, did not. Furthermore, compared to wild types, Akap12 knockout mice showed smaller numbers of both astrocytes and OPCs, along with slower development of corpus callosum after birth. These findings suggest that AKAP12 signaling may be required for postnatal glial formation in the corpus callosum through cell- and non-cell autonomous mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12015-021-10118-wDOI Listing
January 2021

Endoplasmic Reticulum Interaction Supports Energy Production and Redox Homeostasis in Mitochondria Released from Astrocytes.

Transl Stroke Res 2021 Jan 21. Epub 2021 Jan 21.

Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, 149-2401, Charlestown, MA, 02129, USA.

Mitochondria can be released by astrocytes as part of a help-me signaling process in stroke. In this study, we investigated the molecular mechanisms that underlie mitochondria secretion, redox status, and functional regulation in the extracellular environment. Exposure of rat primary astrocytes to NAD or cADPR elicited an increase in mitochondrial calcium through ryanodine receptor (RyR) in the endoplasmic reticulum (ER). Importantly, CD38 stimulation with NAD accelerated ATP production along with increasing glutathione reductase (GR) and dipicolinic acid (DPA) in intracellular mitochondria. When RyR was blocked by Dantrolene, all effects were clearly diminished. Mitochondrial functional assay showed that these activated mitochondria appeared to be resistant to HO exposure and sustained mitochondrial membrane potential, while inhibition of RyR resulted in disrupted membrane potential under oxidative stress. Finally, a gain- or loss-of-function assay demonstrated that treatment with DPA in control mitochondria preserved GR contents and increased mitochondrial membrane potential, whereas inhibiting GR with carmustine decreased membrane potentials in extracellular mitochondria released from astrocytes. Collectively, these data suggest that ER-mitochondrial interaction mediated by CD38 stimulation may support mitochondrial energy production and redox homeostasis during the mode of mitochondrial transfer from astrocytes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12975-021-00892-7DOI Listing
January 2021

Insights from the Applications of Single-Cell Transcriptomic Analysis in Germ Cell Development and Reproductive Medicine.

Int J Mol Sci 2021 Jan 15;22(2). Epub 2021 Jan 15.

Department of Stem Cell and Regenerative Biotechnology, Institute of Advanced Regenerative Science, Konkuk University, Seoul 05029, Korea.

Mechanistic understanding of germ cell formation at a genome-scale level can aid in developing novel therapeutic strategies for infertility. Germ cell formation is a complex process that is regulated by various mechanisms, including epigenetic regulation, germ cell-specific gene transcription, and meiosis. Gonads contain a limited number of germ cells at various stages of differentiation. Hence, genome-scale analysis of germ cells at the single-cell level is challenging. Conventional genome-scale approaches cannot delineate the landscape of genomic, transcriptomic, and epigenomic diversity or heterogeneity in the differentiating germ cells of gonads. Recent advances in single-cell genomic techniques along with single-cell isolation methods, such as microfluidics and fluorescence-activated cell sorting, have helped elucidate the mechanisms underlying germ cell development and reproductive disorders in humans. In this review, the history of single-cell transcriptomic analysis and their technical advantages over the conventional methods have been discussed. Additionally, recent applications of single-cell transcriptomic analysis for analyzing germ cells have been summarized.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22020823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829788PMC
January 2021

Retrospective analysis of current guidelines for hepatocellular carcinoma diagnosis on gadoxetic acid-enhanced MRI in at-risk patients.

Eur Radiol 2021 Jan 3. Epub 2021 Jan 3.

Division of Abdominal Radiology, Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Objective: To evaluate and compare the diagnostic performance of the updated HCC guidelines using gadoxetic acid-enhanced MRI.

Methods: In this study, patients at risk of HCC who underwent gadoxetic acid-enhanced MRI following US/CT surveillance were retrospectively recruited from 3 centers. Three radiologists independently evaluated hepatic nodule imaging features relevant to the diagnostic criteria outlined in each guideline. Per-lesion sensitivity, specificity, and accuracy were compared between guidelines using logistic regression with a generalized estimating equation. Inter-observer agreements on imaging features were determined using Fless κ statistics.

Results: Altogether, 447 nodules (310 HCCs, 20 combined hepatocellular-cholangiocarcinomas, 2 cholangiocarcinomas, and 115 benign entities) measuring 1-3 cm from 386 patients were assessed. The KLCA-NCC and APASL guidelines showed the highest sensitivity (82.3-90.6%, p < .001) and accuracy (83.9-88.6%) among the five guidelines. The OPTN/UNOS guideline showed the highest specificity (94.9-97.1%), followed by the AASLD/LI-RADS, EASL, KLCA-NCC, and APASL guidelines, with significant difference only with the APASL guideline. The diagnostic performance of the updated AASLD/LI-RADS and EASL guidelines and of the KLCA-NCC and APASL guidelines was comparable (p > .05). Inter-observer agreement was substantial to almost perfect (κ = 0.73-0.87).

Conclusions: For the diagnosis of HCC using gadoxetic acid-enhanced MRI, the KLCA-NCC and APASL guidelines showed the highest sensitivity and accuracy. The OPTN/UNOS guideline showed the highest specificity. Acknowledging their relative strengths and weaknesses could help adapt the diagnostic criteria according to the clinical context.

Key Points: • APASL and KLCA-NCC provided significantly the highest sensitivity and accuracy, followed by AASLD/LI-RADS and EASL in an endemic area for hepatitis B. • OPTN/UNOS showed the highest specificity, followed by AASLD/LI-RADS, EASL, KLCA-NCC, and APASL guidelines, with significant difference only with APASL. • Broadened definition of arterial hyperenhancement, washout, and the size of the lesion eligible to apply diagnostic criteria may improve the diagnostic performance for HCC in an endemic area for hepatitis B.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-020-07577-zDOI Listing
January 2021

Changes in Cecal Microbiota and Short-chain Fatty Acid During Lifespan of the Rat.

J Neurogastroenterol Motil 2021 Jan;27(1):134-146

Department of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul, Korea.

Background/aims: The gut microbiota regulates intestinal immune homeostasis through host-microbiota interactions. Multiple factors affect the gut microbiota, including age, sex, diet, and use of drugs. In addition, information on gut microbiota differs depending on the samples. The aim of this study is to investigate whether changes in cecal microbiota depend on aging.

Methods: Gut microbiota in cecal contents of 6-, 31-, and 74-week-old and 2-year-old male Fischer-344 rats (corresponding to 5-, 30-, 60-, and 80-year-old humans in terms of age) were analyzed using 16S ribosomal RNA metagenome sequencing and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) based on the Kyoto Encyclopedia of Genes and Genomes orthology. Moreover, short-chain fatty acid (SCFA) level in cecum and inflammation related factors were measured using real-time quantitative polymerase chain reaction and enzyme linked immunosorbent assay.

Results: Alpha and beta diversity did not change significantly with age. At the family level, Lachnospiraceae and Ruminococcaceae, which produce SCFAs, showed significant change in 31-week-old rats: Lachnospiraceae significantly increased at 31 weeks of age, compared to other age groups, while Ruminococcaceae decreased. Butyrate levels in cecum were significantly increased in 31-week-old rats, and the expression of inflammation related genes was increased followed aging. Especially, EU622775_s and EU622773_s, which were highly abundance species in 31-week-old rats, showed significant relationship with butyrate concentration. Enzymes required for producing butyrate-acetyl-CoA transferase, butyryl-CoA dehydrogenase, and butyrate kinase-were not predicted by PICRUSt.

Conclusions: Major bacterial taxa in the cecal lumen, such as Lachnospiraceae, well-known SCFAs-producing family, changed in 31-week-old rats. Moreover, unknown species EU622775_s and EU622773_s showed strong association with cecal butyrate level at 31 weeks of age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5056/jnm20148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786083PMC
January 2021

Metabolite Profiling of L. Leaves by High-Resolution Mass Spectrometry Coupled with ESI and APCI and In Vitro Antioxidant Activity, α-Glucosidase, and Elastase Inhibition Assays.

Int J Mol Sci 2020 Dec 24;22(1). Epub 2020 Dec 24.

Department of Chemistry, Kyungpook National University, Daegu 41566, Korea.

High-resolution mass spectrometry equipped with electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) sources was used to enhance the characterization of phytochemicals of ethanol extracts of L. leaves (ZLE). Sugar compounds, dicarboxylic acids, compounds of phenolic acids and flavonoids groups, and other phytochemicals were detected from the leaves. Antioxidant activity and inhibition potentiality of ZLE against α-glucosidase enzyme, and elastase enzyme activities were evaluated in in vitro analysis. ZLE significantly inhibited activities of α-glucosidase enzyme at a lower concentration (IC 2.51 ± 0.15 µg/mL). Glucose uptake in C2C12 cells was significantly enhanced by 42.13 ± 0.15% following the treatment with ZLE at 30 µg/mL. It also exhibited potential antioxidant activities and elastase enzyme inhibition activity (IC 27.51 ± 1.70 µg/mL). Atmospheric pressure chemical ionization mass spectrometry (APCI-MS) detected more peaks than electrospray ionization mass spectrometry (ESI-MS), and both ionization techniques illustrated the biological activities of the detected compounds more thoroughly compared to single-mode analysis. Our findings suggest that APCI along with ESI is a potential ionization technique for metabolite profiling, and ZLE has the potential in managing diabetes by inhibiting α-glucosidase activity and enhancing glucose uptake.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22010132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795549PMC
December 2020

Emergency exploratory laparotomy in a COVID-19 patient - A case report.

Anesth Pain Med (Seoul) 2020 Oct 7;15(4):498-504. Epub 2020 Oct 7.

Department of Anesthesiology and Pain Medicine, National Medical Center, Seoul, Korea.

Background: Surgeries in patients with coronavirus disease 2019 (COVID-19) put medical staff at a high risk of infection. We report the anesthetic management and infection control of a mechanically ventilated COVID-19 patient who underwent exploratory laparotomy for suspected duodenal ulcer perforation.

Case: A 73-year-old man, mechanically ventilated for confirmed COVID-19, showed clinical and radiographic signs of a perforated duodenal ulcer, and he was transferred under sedation and intubation to a negative-pressure operating room. The operating and assistant staff wore personal protective equipment. High-efficiency particulate absorbing filters were inserted into the expiratory circuits of the anesthesia machine and portable ventilator. No participating staff contracted COVID-19, although the patient later died due to pneumonia.

Conclusions: This report can contribute to establishing clinical guidelines for the surgical management and operation room setting of COVID-19 patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.17085/apm.20041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724121PMC
October 2020

on : Confirmation in the Korean Peninsula after 82 Years and the First Record in South Korea.

Mycobiology 2020 Sep 14;48(6):518-521. Epub 2020 Sep 14.

Division of Forest Insect Pests and Diseases, National Institute of Forest Science, Seoul, Korea.

has been recorded on several species of in China, Japan, Russia (Far East), and North Korea since its first recorded observation as a rust fungus on in Jilin, China, in 1899. In the Korean Peninsula, the rust fungus was first recorded on in 1935, based on four specimens collected at Mt. Kumgangsan, Gangwondo Province, in the North Korean territory. We confirmed this rust in the Korean Peninsula after 82 years. The rust fungus was identified based on morphological characteristics and a molecular phylogenetic analysis. This is the first record of in South Korea.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/12298093.2020.1816155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717706PMC
September 2020

Taxonomic Study of the Genus (Strophariaceae, Basidiomycota) in Korea.

Mycobiology 2020 Oct 22;48(6):476-483. Epub 2020 Oct 22.

School of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul, Republic of Korea.

The genus (Strophariaceae, Basidiomycota) is made up of wood-rotting saprotrophic mushrooms characterized by a yellow or brown pileus with scales and/or slimy, and by a brownish smooth spore with a germ pore. However, these features are not enough to distinguish its species, or separate the genus from other brown-spored wood-rotting genera such as and . Although internal transcribed spacer (ITS) sequence-based identification has improved identification accuracy for species of , most species in Korea are reported based on morphological features. To evaluate the taxonomy of species, we investigated 62 specimens collected from 1999 to 2019 in Korea using ITS sequence analysis and morphological observation. Twelve of the 16 recorded species in Korea were identified. While eight species were clearly separated, the ITS analysis did not distinguish three in the complex. Therefore, further investigation is required to distinguish these three species. ITS sequences deposited in GenBank confirm that exists in Korea. The presence of the other four species could not be confirmed through specimens or sequence information in GenBank. A taxonomic key and the ITS sequence data for Korean species are included and can be good baselines for further research on taxonomy and diversity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/12298093.2020.1831427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717605PMC
October 2020

from Rhizosphere Soil in Terrestrial and Coastal Environments in South Korea.

Mycobiology 2020 Oct 16;48(6):431-442. Epub 2020 Oct 16.

School of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul, Republic of Korea.

, the most common genus plays an important ecological role in various terrestrial and marine environments. However, only a few species have been reported from rhizosphere soil. As part of a project to excavate Korean indigenous fungi, we investigated rhizosphere soil of six plants in the forest (terrestrial habitat) and sand dunes (coastal habitat) and focused on discovering species. A total of 64 strains were isolated and identified as 26 species in nine sections based on morphological characteristics and the sequence analysis of β-tubulin and calmodulin. Although this is a small-scale study in a limited rhizosphere soil, eight unrecorded species and four potential new species have been identified. In addition, most species from rhizosphere soil were unique to each plant. , , , , and were commonly isolated from rhizosphere soil. Eight species, , and were recorded for the first time in Korea. Here, we provide the detailed morphological description of these unrecorded species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/12298093.2020.1823611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717687PMC
October 2020

Prediction of Infarct Growth and Neurological Deterioration in Patients with Vertebrobasilar Artery Occlusions.

J Clin Med 2020 Nov 22;9(11). Epub 2020 Nov 22.

Department of Neurology, Ajou University School of Medicine, 164, World cup-ro, Yeongtong-gu, Suwon, Gyeonggi-do 16499, Korea.

We aimed to identify predictors of infarct growth and neurological deterioration (ND) in vertebrobasilar occlusions (VBOs) with a focus on clinical-core mismatch. From 2010 to 2018, VBO patients were selected from a university hospital registry. In total, 138 VBO patients were included. In these patients, a posterior circulation Alberta Stroke Program Early CT score (PC-ASPECTS) less than 6 was associated with futile outcome. Within patients with feasible cores, a decrease in PC-ASPECTS score of 2 or more on follow-up imaging was classified as infarct growth and could be predicted by a National Institutes of Health Stroke Scale (NIHSS) mental status subset of 1 or higher (odds ratio (OR): 3.34, 95% confidence interval (CI) (1.19-9.38), = 0.022). Among the 73 patients who did not undergo reperfusion therapy, 13 patients experienced ND (increase in discharge NIHSS score of 4 or more compared to the initial presentation). Incomplete occlusion (vs. complete occlusion, OR 6.17, 95% CI (1.11-34.25), = 0.037), poorer collateral status (BATMAN score, OR: 1.91, 95% CI (1.17-3.48), = 0.009), and larger infarct cores (PC-ASPECTS, OR: 1.96, 95% CI (1.11-3.48), = 0.021) were predictive of ND. In patients with VBO, an initial PC-ASPECTS of 6 or more, but with a decrease in the mental status subset of 1 or more can predict infarct growth, and may be used as a criterion for clinical-core mismatch. ND in VBO patients presenting with milder symptoms can be predicted by incomplete occlusion, poor collaterals, and larger infarct cores.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9113759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700123PMC
November 2020

AKAP12 Supports Blood-Brain Barrier Integrity against Ischemic Stroke.

Int J Mol Sci 2020 Nov 28;21(23). Epub 2020 Nov 28.

Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Boston, MA 02129, USA.

A-kinase anchor protein 12 (AKAP12) is a scaffolding protein that associates with intracellular molecules to regulate multiple signal transductions. Although the roles of AKAP12 in the central nervous system are still relatively understudied, it was previously shown that AKAP12 regulates blood-retinal barrier formation. In this study, we asked whether AKAP12 also supports the function and integrity of the blood-brain barrier (BBB). In a mouse model of focal ischemia, the expression level of AKAP12 in cerebral endothelial cells was upregulated during the acute phase of stroke. Also, in cultured cerebral endothelial cells, oxygen-glucose deprivation induced the upregulation of AKAP12. When AKAP12 expression was suppressed by an siRNA approach in cultured endothelial cells, endothelial permeability was increased along with the dysregulation of ZO-1/Claudin 5 expression. In addition, the loss of AKAP12 expression caused an upregulation/activation of the Rho kinase pathway, and treatment of Rho kinase inhibitor Y-27632 mitigated the increase of endothelial permeability in AKAP12-deficient endothelial cell cultures. These in vitro findings were confirmed by our in vivo experiments using knockout mice. Compared to wild-type mice, knockout mice showed a larger extent of BBB damage after stroke. However, the inhibition of rho kinase by Y-27632 tightened the BBB in knockout mice. These data may suggest that endogenous AKAP12 works to alleviate the damage and dysfunction of the BBB caused by ischemic stress. Therefore, the AKAP12-rho-kinase signaling pathway represents a novel therapeutic target for stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21239078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730430PMC
November 2020

Reactive oxygen species modulator 1 expression predicts lymph node metastasis and survival in early-stage non-small cell lung cancer.

PLoS One 2020 1;15(12):e0239670. Epub 2020 Dec 1.

Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.

Reactive oxygen species modulator 1 (romo1) causes cell hyperplasia and promotes cancer cell invasion. Based recent studies, the overexpression of romo1 is associated with lymphatic metastasis and poor prognosis in lung cancer. We aimed to evaluate associations between romo1 expression and lymph node metastasis in non-small cell lung cancer (NSCLC). Clinical data and pathological results were retrospectively reviewed for 98 subjects diagnosed with NSCLC and who underwent surgical biopsy between 1994 and 2009. A total 98 tumor specimens were analyzed. The romo1 H score was correlated with stage and was significantly higher in subjects with lymph node metastasis than in those without metastasis (173 vs 116; P < 0.05). The area (%) of grade 1 expression was significantly smaller (19.5 vs 37.0; P = 0.005) and the area of grade 3 expression was significantly larger (27.9 vs 6.00; P < 0.001) in subjects with lymph node metastasis than in those without metastasis. In stage I patients, disease free survival (DFS) (191 ± 18.8 vs. 75.6 ± 22.4 months, P = 0.004) was significantly longer in the low romo1 group than in the high romo1 group. A multivariate analysis showed a significant association between high romo1 expression and poor DFS (hazard ratio 5.59, 95 confidence interval, 1.54-20.3, P = 0.009). These findings support the prognostic value of romo1 in NSCLC, especially in stage I.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239670PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707601PMC
January 2021

Effects of O-GlcNAcylation on functional mitochondrial transfer from astrocytes.

J Cereb Blood Flow Metab 2020 Nov 5:271678X20969588. Epub 2020 Nov 5.

Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.

Mitochondria may be transferred from cell to cell in the central nervous system and this process may help defend neurons against injury and disease. But how mitochondria maintain their functionality during the process of release into extracellular space remains unknown. Here, we report that mitochondrial protein O-GlcNAcylation is a critical process to support extracellular mitochondrial functionality. Activation of CD38-cADPR signaling in astrocytes robustly induced protein O-GlcNAcylation in mitochondria, while oxygen-glucose deprivation and reoxygenation showed transient and mild protein modification. Blocking the endoplasmic reticulum - Golgi trafficking with Brefeldin A or slc35B4 siRNA reduced O-GlcNAcylation, and resulted in the secretion of mitochondria with decreased membrane potential and mtDNA. Finally, loss-of-function studies verified that O-GlcNAc-modified mitochondria demonstrated higher levels of neuroprotection after astrocyte-to-neuron mitochondrial transfer. Collectively, these findings suggest that post-translational modification by O-GlcNAc may be required for supporting the functionality and neuroprotective properties of mitochondria released from astrocytes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0271678X20969588DOI Listing
November 2020

Corrigendum to "Xanthii fructus extract inhibits TNF-α/IFN-γ-induced Th2-chemokines production via blockade of NF-κB, STAT1 and p38-MAPK activation in human epidermal keratinocytes" [J. Ethnopharmacol. 171 (2015) 85-93].

J Ethnopharmacol 2021 Feb 11;266:113450. Epub 2020 Oct 11.

College of Pharmacy, Keimyung University, 1095 Dalgubeoldaero, Dalseo-Gu, Daegu, 42601, Republic of Korea. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2020.113450DOI Listing
February 2021