• Nutrition Research and Practice
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• v.12 no.2
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• pp.101-109
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• 2018

BACKGROUD/OBJECTIVES: The objective of this study was to investigate the effects of vitamin C on inflammation, tumor development, and dysbiosis of intestinal microbiota in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced inflammation-associated early colon cancer mouse model. MATERIALS/METHODS: Male BALB/c mice were injected intraperitoneally with AOM [10 mg/kg body weight (b.w)] and given two 7-d cycles of 2% DSS drinking water with a 14 d inter-cycle interval. Vitamin C (60 mg/kg b.w. and 120 mg/kg b.w.) was supplemented by gavage for 5 weeks starting 2 d after the AOM injection. RESULTS: The vitamin C treatment suppressed inflammatory morbidity, as reflected by disease activity index (DAI) in recovery phase and inhibited shortening of the colon, and reduced histological damage. In addition, vitamin C supplementation suppressed mRNA levels of pro-inflammatory mediators and cytokines, including cyclooxygenase-2, microsomal prostaglandin E synthase-2, tumor necrosis $factor-{\alpha}$, Interleukin $(IL)-1{\beta}$, and IL-6, and reduced expression of the proliferation marker, proliferating cell nuclear antigen, compared to observations of AOM/DSS animals. Although the microbial composition did not differ significantly between the groups, administration of vitamin C improved the level of inflammation-related Lactococcus and JQ084893 to control levels. CONCLUSION: Vitamin C treatment provided moderate suppression of inflammation, proliferation, and certain inflammation-related dysbiosis in a murine model of colitis associated-early colon cancer. These findings support that vitamin C supplementation can benefit colonic health. Long-term clinical studies with various doses of vitamin C are warranted.

• Clinical and Experimental Reproductive Medicine
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• v.32 no.3
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• pp.223-230
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• 2005

Objective: This study was performed to evaluate the accuracy of hysterosalpingography (HSG) for evaluating female infertility patients by comparison with hysteroscopic and laparoscopic examination. Methods and Material: Total 219 infertile patients were retrospectively analyzed between January 1, 2002 and December 31, 2003. Ninety seven patients (44.3%) were primary infertility, 122 patients (55.7%) were secondary infertility. We performed hysteroscopic and laparoscopic examination on next cycle when HSG revealed any abnormal finding, and 3~6 cycles later if HSG was normal. Results: The accuracy of HSG was 65.2% compared with hysteroscopic examination (sensitivity 88.4%, specificity 46.4%, false positive rate 53.6%, false negative rate 11.6%). The most common abnormal finding of hysteroscopy was uterine synechia (67.4%) followed by endometrial polyp, uterine anomaly (e.g. uterine septum), endometrial hyperplasia. Compared with laparoscopic examination, the accuracy of HSG was 76.9% (sensitivity 98.9%, specificity 70.6%, +LR 3.36, -LR 0.02). The positive predictive value of normal patent tube was excellent (99.6%) but that of proximal tubal blockage was only 46.7%. The unilateral tubal obstruction of HSG was poor accuracy (+LR 3.85 -LR 0.68) and 70% of those was patent by laparoscopic examination. Laparoscopic examination also revealed that 53% of patients had peritubal adhesion and 37% of patients has additional pelvic findings, especially endometriosis. Among the patients had normal HSG, 53.5% patients with normal ultrasonography was diagnosed endometriosis (25.6% of them had endometriosis stage I-II). Conclusion: Normal HSG shows a high negative predictive value. Nevertheless, the incidence of associated pelvic disease in the normal HSG group is high enough to warrant diagnostic laparoscopy if nonsurgical treatment is unsuccessful. Because HSG has poor accuracy in predicting distal tubal blockage and peritubal adhesion, and poor positive predictive value of proximal tubal blockage, laparoscopic examination could be considered in abnormal HSG group.

• BMB Reports
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• v.54 no.10
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• pp.505-515
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• 2021

Human pluripotent stem cells (hPSCs) include human embryonic stem cells (hESCs) derived from blastocysts and human induced pluripotent stem cells (hiPSCs) generated from somatic cell reprogramming. Due to their self-renewal ability and pluripotent differentiation potential, hPSCs serve as an excellent experimental platform for human development, disease modeling, drug screening, and cell therapy. Traditionally, hPSCs were considered to form a homogenous population. However, recent advances in single cell technologies revealed a high degree of variability between individual cells within a hPSC population. Different types of heterogeneity can arise by genetic and epigenetic abnormalities associated with long-term in vitro culture and somatic cell reprogramming. These variations initially appear in a rare population of cells. However, some cancer-related variations can confer growth advantages to the affected cells and alter cellular phenotypes, which raises significant concerns in hPSC applications. In contrast, other types of heterogeneity are related to intrinsic features of hPSCs such as asynchronous cell cycle and spatial asymmetry in cell adhesion. A growing body of evidence suggests that hPSCs exploit the intrinsic heterogeneity to produce multiple lineages during differentiation. This idea offers a new concept of pluripotency with single cell heterogeneity as an integral element. Collectively, single cell heterogeneity is Janus-faced in hPSC function and application. Harmful heterogeneity has to be minimized by improving culture conditions and screening methods. However, other heterogeneity that is integral for pluripotency can be utilized to control hPSC proliferation and differentiation.

• Molecules and Cells
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• v.44 no.9
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• pp.688-695
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• 2021

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has become a global health concern. Various SARS-CoV-2 vaccines have been developed and are being used for vaccination worldwide. However, no therapeutic agents against coronavirus disease 2019 (COVID-19) have been developed so far; therefore, new therapeutic agents are urgently needed. In the present study, we evaluated several hepatitis C virus direct-acting antivirals as potential candidates for drug repurposing against COVID-19. Theses include asunaprevir (a protease inhibitor), daclatasvir (an NS5A inhibitor), and sofosbuvir (an RNA polymerase inhibitor). We found that asunaprevir, but not sofosbuvir and daclatasvir, markedly inhibited SARS-CoV-2-induced cytopathic effects in Vero E6 cells. Both RNA and protein levels of SARS-CoV-2 were significantly decreased by treatment with asunaprevir. Moreover, asunaprevir profoundly decreased virion release from SARS-CoV-2-infected cells. A pseudoparticle entry assay revealed that asunaprevir blocked SARS-CoV-2 infection at the binding step of the viral life cycle. Furthermore, asunaprevir inhibited SARS-CoV-2 propagation in human lung Calu-3 cells. Collectively, we found that asunaprevir displays broad-spectrum antiviral activity and therefore might be worth developing as a new drug repurposing candidate for COVID-19.

• Journal of The Korean Society of Integrative Medicine
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• v.9 no.2
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• pp.105-108
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• 2021

Background : Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare, autosomal recessive metabolic disorder which is caused by genetic mutations that disrupt the urea cycle. It is characterized by variable clinical presentation and the age of onset. Patients may present with gait disturbance and progressive paraplegia and muscle tightness in the lower extremities. The use of botulinum toxin in metabolic disease has rarely been discussed. We describe a case of a 14-year-old-boy with HHH syndrome, who presented with a several - month history of gait disturbance and lower extremity weakness. Case presentation : A 14-year old male had a history of recurrent upper respiratory tract infections, occasional vomiting, loss of appetite, and general weakness, all of which started since he was 10 months old. He was diagnosed with HHH syndrome at one year of age. At the age of 14, he was referred for the assessment and treatment of his gait disturbance and aggravated weakness of the lower extremities. Brain MRI, electrodiagnostic study and blood test were performed to exclude any lesions related to neurologic dysfunction. Botulinum toxin type A were injected into muscles of adductor longus, adductor magnus, lateral and medial hamstring, and lateral and medial gastrocnemius muscle heads under needle electromyography guidance to reduce lower limb spasticity. Intensive physical therapy including gait training and stretching exercise of adductor and calf muscles were also provided. After intensive physical therapy and botulinum toxin injection to reduce lower limb spasticity, he was able to ambulate for 20 meters independently without any walking aids. There were no adverse events after the injection. Conclusion : Botulinum toxin injection is a safe and effective therapy for patients with HHH syndrome who suffer from gait disturbance.

• Journal of Korean Traditional Oncology
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• v.23 no.2
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• pp.11-25
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• 2018

Objective: The purpose of this study is to report the case of a patient with non-small cell lung cancer (NSCLC) with Programmed cell death protein 1 (PD-1) mutation treated by Integrative Medicine Therapy (IMT). Methods: A patient with metastatic NSCLC received pembrolizumab 200mg intravenously for every 3 weeks from July 2017. Repeat cycle every 3 weeks since July 2017. The patient has been treated with Integrative Medicine Therapy (IMT) since December 2016. The tumor size was measured by computed tomography (CT) and magnetic resonance imaging(MRI). Adverse events were evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. Results: After combined treatment, the extent of proximal portion of primary tumor in the left lower lobe was decreased and disease status was stable radiologically. No evidence of newly developed metastatic lesions in the brain since May 2017. The patient did not experience any adverse event according to NCI-CTCAE ver. 5.0. Conclusion: This case study suggests that Integrative Medicine Therapy (IMT) may contribute to tumor response, in conjunction with Pembrolizumab on the treatment of patients with NSCLC.

• Perinatology
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• v.29 no.4
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• pp.189-194
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• 2018

Congenital neuroblastoma is a rare disease. Placental metastasis is extremely rare and poor prognosis has been reported in neonates. Mirror syndrome could occur in mother with placental metastasis with possibilities of hypertension and edema. We report a case of detection of left suprarenal mass in fetus at $31^{+5}weeks^{\prime}$ gestation. Mother presented with palpitation, edema, headache, and hypertension. Maternal 24 hours urine vanillylmandelic acid (VMA) and normetanephrine (NME) level at 34 weeks' gestation were elevated. Consequently, emergent cesarean section was done. Based on abdominal ultrasonography and whole body magnetic resonance imaging, left adrenal tumor with liver metastasis was suspected. Neuroblastoma was confirmed by liver and placenta biopsy. Chemotherapy was started with Pediatric Oncology Group 9243 at day 7 and changed into Children's Oncology Group 3961 due to cholestasis and poor response during 2nd cycle. Plasma exchange was done for aggravated direct hyperbilirubinemia. The baby expired at 73 days due to multi-organ failure. Maternal symptoms were completely resolved in 2 weeks after delivery along with normalization of the elevated level of VMA and NME. We report a first case of mirror syndrome in Korean mother and fetus resulting from metastatic congenital neuroblastoma to placenta.

• Microbiology and Biotechnology Letters
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• v.49 no.4
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• pp.510-518
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• 2021

Bacteriophages are considered excellent sensing elements for platforms detecting bacteria. However, their lytic cycle has restricted their efficacy. Here, we used the minor coat protein pIII domain (N1N2) of phage CTXφ to construct a novel surface plasmon resonance (SPR) biosensor that could detect Vibrio cholerae. N1N2 harboring the domains required for phage adsorption and entry was obtained from Escherichia coli using recombinant protein expression and purification. SDS-PAGE revealed an approximate size of 30 kDa for N1N2. Dot blot and transmission electron microscopy analyses revealed that the protein bound to the host V. cholerae but not to non-host E. coli K-12 cells. Next, we used amine-coupling to develop a novel recombinant N1N2 (rN1N2)-functionalized SPR biosensor by immobilizing rN1N2 proteins on gold substrates and using SPR to monitor the binding kinetics of the proteins with target bacteria. We observed rapid detection of V. cholerae in the range of approximately 10³ to 10⁹ CFU/ml but not of E. coli at any tested concentration, thereby confirming that the biosensor exhibited differential recognition and binding. The results indicate that the novel biosensor can rapidly monitor a target pathogenic microorganism in the environment and is very useful for monitoring food safety and facilitating early disease prevention.

• Research in Plant Disease
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• v.27 no.4
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• pp.137-148
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• 2021

Plant RNA viruses are one of the most destructive pathogens that cause a significant loss in crop production worldwide. They have evolved with high genetic diversity and adaptability due to the short replication cycle and high mutation rate during genome replication, which are characteristics of RNA viruses. Plant RNA viruses exist as quasispecies with high genetic diversity; thereby, a rapid population transition with new fitness can occur due to selective pressure resulting from environmental changes. Plant resistance can act as selective pressure and affect the fitness of the virus, which may lead to the emergence of resistance-breaking variants. In this paper, we introduced the evolutionary perspectives of plant RNA viruses and the driving forces in their evolution. Based on this, we discussed the mechanism of the emergence of variant viruses that overcome plant resistance. In addition, strategies for deploying plant resistance to viral diseases and improving resistance durability were discussed.

• Korean Journal of Acupuncture
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• v.38 no.4
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• pp.222-234
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• 2021

Objectives : The purpose of this study is to examine the efficacy of fire needling and warm needling for De Quervain Syndrome by reviewing clinical studies for recent 10 years. Methods : Randomized controlled trials, non-randomized controlled trials, and case series containing more than 20 cases about fire needling and warm needling for De Quervain Syndrome published since 2011 were searched through four foreign online databases (CNKI, Pubmed, EMBASE, Cochrane Library) and five Korean online databases (OASIS, Science ON, DBPIA, KISS, RISS). The number and characteristics of participants, treatment points and main treatment methods involving other combination treatments, treatment cycle or total periods of treatments, evaluation indices, efficacy, and adverse events were analyzed. Risk of bias of included randomized clinical trials was assessed using a revised tool for assessing risk of bias in randomized trials (RoB 2). Results : A total of 6 randomized clinical trials and 2 case series involving 471 participants were included. Tender point or 'Ashi point' was the most commonly used treatment point, followed by LU4. Treatment frequency ranged from once a day to once a week. One to three outcome measures were used to evaluate the results of the studies, with the efficacy rate the most frequently used, followed by visual analogue scale. Overall risk of bias of all included randomized clinical trials was judged to have some concerns. Conclusions : All selected studies showed that fire needling and warm needling treatments for De Quervain syndrome were more effective than other clinical methods or acupuncture treatments. However, as the number of clinical studies is still too small and the risk of bias of the studies is not low, it is believed that more systematic and objective studies should be conducted.