Search

Background: Herbal medicine Ja-Geum-Jeong (JGJ) has been used for the treatment of detoxification in Eastern Asia. However, the mechanisms involved are not clearly defined. The purpose of the present study was to investigate if herb medication inhibits Methamphetamine (METH)'s reinforcing effect and also examined if a combination of herb medication and acupuncture produces a synergistic effect on METH., Methods: Male Sprague-Dawley rats were given acute METH intraperitoneally and the locomotor activity and ultrasonic vocalization (USV) calls were measured. Rats were administered JGJ orally and acupuncture was given at HT7 or SI5. Monosodium glutamate (MSG) and gamma-aminobutyric acid (GABA) agonists were injected into the Central amygdala (CeA) to investigate a possible neuroscientific mechanism. Tyrosine hydroxylase (TH) and fast scan cyclic voltammetry (FSCV) were measured to immunohistochemically and electrically confirm the behavioral data., Results: Locomotor activity and USV calls were increased by METH ( P < 0.05) and these increases were inhibited by JGJ ( P < 0.05). Also, JGJ had no effect on the normal group given saline, and acupuncture at SI5 acupoint, but not at HT7 acupoint, produced a synergistic effect when combined with JGJ ( P < 0.05). The JGJ's inhibition was blocked by the inactivation of CeA ( P < 0.05), and MSG mimicked JGJ ( P < 0.05). TH and FSCV measures showed the same pattern with the behavioral data ( P < 0.05)., Conclusion: Results of the present study suggest that JGJ had inhibitory effects on the METH which was mediated through the activation of CeA and that combination of acupuncture and herb produced synergistic effect., Competing Interests: The authors declare no competing interests., (© 2024 Korea Institute of Oriental Medicine. Published by Elsevier B.V.)

Background: Our previous studies proved that neurogenic inflammatory spots (or neurogenic spots) have the same physiological features as acupuncture points and that neurogenic spot stimulation generates therapeutic effects in various animal models. However, it is unclear how deeply the neurogenic spots should be stimulated to generate therapeutic effects., Methods: The effects of acupuncture at various needle depths below the neurogenic spot were examined in a rat immobilization stress-induced hypertension (IMH) model. Electroacupuncture was applied to a neurogenic spot at depths of 1, 2, or 3 mm using a concentric bipolar electrode., Results: Electrical stimulation of the neurogenic spot at a 3-mm depth most effectively lowered blood pressure compared with controls and stimulation at 1- and 2-mm depths, which was inhibited by pretreatment with a local anesthetic lidocaine. Electrical stimulation of the neurogenic spot or injection of substance P (SP) at a 3-mm depth significantly excited the rostral ventrolateral medulla (rVLM) compared with superficial stimulation. Electrical stimulation applied at a 3-mm depth on neurogenic spots dominantly caused c-fos expression from rVLM and ventrolateral periaqueductal gray (vlPAG) in IMH rats. Pretreatment with resiniferatoxin (RTX) injection into the neurogenic spot to ablate SP or calcitonin gene-related peptide (CGRP) prevented the effects of 3-mm neurogenic spot stimulation on blood pressure in IMH rats. Conversely, artificial injection of SP or CGRP generated anti-hypertensive effects in IMH rats., Conclusion: Our data suggest that neurogenic spot stimulation at a 3-mm depth generated anti-hypertensive effects through the local release of SP and CGRP and activation of rVLM and vlPAG., (© 2024 Korea Institute of Oriental Medicine. Published by Elsevier B.V.)

Background: There is growing evidence on the important role of non-human leukocyte antigen (HLA) antibodies in lung and heart transplant rejection. Since data on the prevalence and clinical significance of non-HLA antibodies in the Asian population are scarce, we analyzed non-HLA antibodies in heart and lung transplant patients., Methods: We used the Luminex method to measure non-HLA antibodies in patients who underwent heart transplantation (N = 28) or lung transplantation (N = 36) between 2016 and 2019. We evaluated the association between pre-existing non-HLA antibodies and acute rejection-free days in these recipients., Results: Of 64 patients, 27 (42.2%) patients underwent rejection, with 26 (40.6%) acute cellular rejection and one (1.6%) acute antibody-mediated rejection. Among 33 identified different non-HLA antibodies, only the anti-glutathione S-transferase theta-1 (GSTT1) antibody positive rate was significantly higher in patients with acute rejection compared to those without rejection (14.8% vs. 0%, p = 0.016). The angiotensin II type I receptor positive rate was not significantly different between the two groups (40% vs. 18.5%, p = 0.129). In the multivariate Cox regression analysis, anti-GSTT1 antibody-positive patients had a higher risk of acute allograft rejection (hazard ratio, 4.19; 95% confidence interval [CI], 1.41-12.49; p = 0.010). The Kaplan-Meier curve showed that anti-GSTT1 antibody-positive patients had fewer acute rejection-free days (χ 2  = 7.892; p = 0.005). Additionally, patients who underwent platelet transfusion (odds ratio, 1.49; 95% CI, 1.16-1.91; p = 0.002) before transplantation were more likely to be positive for anti-GSTT1 antibody., Conclusion: Patients with antibodies against GSTT1 before heart or lung transplantation have an increased risk of acute rejection., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: IQSEC3, a gephyrin-binding GABAergic (gamma-aminobutyric acidergic) synapse-specific guanine nucleotide exchange factor, was recently reported to regulate activity-dependent GABAergic synapse maturation, but the underlying signaling mechanisms remain incompletely understood., Methods: We generated mice with conditional knockout (cKO) of Iqsec3 to examine whether altered synaptic inhibition influences hippocampus-dependent fear memory formation. In addition, electrophysiological recordings, immunohistochemistry, and behavioral assays were used to address our question., Results: We found that Iqsec3-cKO induces a specific reduction in GABAergic synapse density, GABAergic synaptic transmission, and maintenance of long-term potentiation in the hippocampal CA1 region. In addition, Iqsec3-cKO mice exhibited impaired fear memory formation. Strikingly, Iqsec3-cKO caused abnormally enhanced activation of ribosomal P70-S6K1-mediated signaling in the hippocampus but not in the cortex. Furthermore, inhibiting upregulated S6K1 signaling by expressing dominant-negative S6K1 in the hippocampal CA1 of Iqsec3-cKO mice completely rescued impaired fear learning and inhibitory synapse density but not deficits in long-term potentiation maintenance. Finally, upregulated S6K1 signaling was rescued by IQSEC3 wild-type, but not by an ARF-GEF (adenosine diphosphate ribosylation factor-guanine nucleotide exchange factor) inactive IQSEC3 mutant., Conclusions: Our results suggest that IQSEC3-mediated balanced synaptic inhibition in hippocampal CA1 is critical for the proper formation of hippocampus-dependent fear memory., (Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Parkinson's disease (PD) is a neurodegenerative disease involving dopaminergic neuronal death in the substantia nigra (SN); recent studies have shown that interactions between gut and brain play a critical role in the pathogenesis of PD. In this study, the anti-inflammatory effect of Korean red ginseng (KRG) and the changes in gut microbiota were evaluated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. Male nine-week-old C57BL/6 mice were injected intraperitoneally with 30 mg/kg of MPTP at 24-h intervals for 5 days. Two hours after the daily MPTP injection, the mice were orally administered 100 mg/kg of KRG, which continued for 7 days beyond the MPTP injections, for a total of 12 consecutive days. Eight days after the final KRG administration, the pole and rotarod tests were performed and brain and colon samples of the mice were collected. Dopaminergic neuronal death, activation of microglia and astrocytes, α-synuclein and expressions of inflammatory cytokines and disruption of tight junction were evaluated. In addition, 16S ribosomal RNA gene sequencing of mouse fecal samples was performed to investigate microbiome changes. KRG treatment prevented MPTP-induced behavioral impairment, dopaminergic neuronal death, activation of microglia and astrocytes in the nigrostriatal pathway, disruption of tight junction and the increase in α-synuclein, interleukin-1β and tumor necrosis factor-α expression in the colon. The 16S rRNA sequencing revealed that MPTP altered the number of bacterial species and their relative abundances, which were partially suppressed by KRG treatment. Especially, KRG suppressed the abundance of the inflammation-related phylum Verrucomicrobia and genera Ruminococcus and Akkermansia (especially Akkermansia muciniphila), and elevated the abundance of Eubacterium, which produces the anti-inflammatory substances. These findings suggest that KRG prevents MPTP-induced dopaminergic neuronal death, activation of microglia and astrocytes, and accumulation of α-synuclein in the SN, and the regulation of inflammation-related factors in the colon may influence the effect., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Acupuncture has been used to treat a wide variety of diseases, disorders, and conditions for more than 2500 years. While the anatomical structures of acupuncture points (or acupoints) are largely unknown, our previous studies have suggested that many acupoints can be identified as cutaneous neurogenic inflammatory spots (neurogenic spots or Neuro-Sps), arising from the release of neuropeptides from activated small diameter sensory afferents at topographically distinct body surfaces due to the convergence of visceral and somatic afferents. In turn, the neuropeptides released during neurogenic inflammation may play important roles in the effects of acupuncture as well as the formation of active acupoints. Thus, the present study has focused on the role of substance P (SP) in acupuncture signal transduction and effects., Methods: Neuro-Sps were detected by using in vivo fluorescence imaging after intravenous injection of Evans blue dye (EBD) and compared with traditional acupoints. Stimulatory effects of the Neuro-Sps were examined in a rat model of immobilization-induced hypertension (IMH). The roles of increased SP in Neuro-Sps were also investigated by using immunohistochemistry, in vivo single-fiber peripheral nerve recordings, and in vivo midbrain extracellular recordings., Results: Neurogenic inflammation quickly appeared at acupoints on the wrist and was fully developed within 15 min in IMH model. The Neuro-Sps showed an increased release of SP from afferent nerve terminals. Mechanical stimulation of these Neuro-Sps increased cell excitability in the midbrain (rostral ventrolateral medulla) and alleviated the development of hypertension, which was blocked by the local injection of the SP receptor antagonist CP-99994 into Neuro-Sps prior to acupuncture and mimicked by the local injection of capsaicin. Single fiber recordings of peripheral nerves showed that increased SP into the Neuro-Sps elevated the sensitivity of A- and C-fibers in response to acupuncture stimulation. In addition, the discharge rates of spinal wide dynamic response (WDR) neurons significantly increased following SP or acupuncture treatment in Neuro-Sps in normal rats, but decreased following the injection of CP-99994 into Neuro-Sps in IMH rats., Conclusions: Our findings suggest that SP released during neurogenic inflammation enhances the responses of sensory afferents to the needling of acupoints and triggers acupuncture signaling to generate acupuncture effects., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Rumex japonicus Houtt. (RJ) is widely distributed in Korea, Japan, and China. The root of RJ has traditionally been used to treat constipation, jaundice, hematemesis, dysfunctional uterine bleeding, and gastrointestinal diseases. According to recent studies, plants of the genus Rumex have beneficial functionalities such as anti-microbial, antioxidative, and anti-inflammatory effects. Inflammatory bowel disease, including Crohn's disease and ulcerative colitis, is a chronic inflammatory disease characterized by an abnormal immune response and epithelial barrier dysfunction. This study evaluates the protective effect of RJ against dextran sulfate sodium (DSS)-induced colitis., Methods: Male 8-week-old C57BL/6 N mice were treated with methanolic extract of RJ for 14 days, and DSS-induced groups were administered 2.5% DSS for last 7 days. After sacrifice, the length and weight of the colon were measured, and colon sections were subjected to H&E staining, immunohistochemistry and Western blotting to investigate the changes of inflammatory cytokines, tight junction and apoptosis-related factors., Results: The colon of DSS-treated mouse was significantly shorter and heavier than the normal mouse. Moreover, DSS exposure induced an increase of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, occludin, zonula occludens-1, p21, p53 and Bcl-2, and decreased the expressions of IL-10, claudin-2 and cleaved caspase-3 in the colon tissue. These DSS-induced changes were inhibited by RJ treatment., Conclusion: Our results indicate that RJ effectively suppresses DSS-induced colitis by protecting tight junction connections in the colonic tissue. We therefore infer that RJ has the potential as a medicine or ingredient for treating colitis., (© 2020 Korea Institute of Oriental Medicine. Publishing services by Elsevier B.V.)

Background: Growing evidence suggests that mechanical stimulation modulates substrates in the supraspinal central nervous system (CNS) outside the canonical somatosensory circuits., Objective/methods: We evaluate mechanical stimulation applied to the cervical spine at the C7-T1 level (termed "MStim") on neurons and neurotransmitter release in the mesolimbic dopamine (DA) system, an area implicated in reward and motivation, utilizing electrophysiological, pharmacological, neurochemical and immunohistochemical techniques in Wistar rats., Results: Low frequency (45-80 Hz), but not higher frequency (115 Hz), MStim inhibited the firing rate of ventral tegmental area (VTA) GABA neurons (52.8% baseline; 450 s) while increasing the firing rate of VTA DA neurons (248% baseline; 500 s). Inactivation of the nucleus accumbens (NAc), or systemic or in situ antagonism of delta opioid receptors (DORs), blocked MStim inhibition of VTA GABA neuron firing rate. MStim enhanced both basal (178.4% peak increase at 60 min) and evoked DA release in NAc (135.0% peak increase at 40 min), which was blocked by antagonism of DORs or acetylcholine release in the NAc. MStim enhanced c-FOS expression in the NAc, but inhibited total expression in the VTA, and induced translocation of DORs to neuronal membranes in the NAc., Conclusion: These findings demonstrate that MStim modulates neuron firing and DA release in the mesolimbic DA system through endogenous opioids and acetylcholine in the NAc. These findings demonstrate the need to explore more broadly the extra-somatosensory effects of peripheral mechanoreceptor activation and the specific role for mechanoreceptor-based therapies in the treatment of substance abuse., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2019. Published by Elsevier Inc.)

The biocompatibility of a recently developed Ni-free Ti-16Nb-3Mo-1Sn (at.%) superelastic alloy was investigated both in vitro and in vivo. In addition, static water contact angle (WCA) and electrochemical tests were carried out. Commercial purity Ti (cp-Ti), which is already being used as a clinical material, was used as the control material. The alloy showed a stable corrosion behavior similar to that of the cp-Ti. The WCA measurements showed that the alloy exhibited hydrophilic properties that contributed to cell attachment to implants, as evident by the cytocompatibility tests. According to the in vivo implantation tests conducted on 30 adult BALB/c rats for periods up to 12 weeks, the tissue reaction around the implants was similar for both the cp-Ti and the alloy, and no significant difference was found in almost all parameters analyzed. Due to its stable superelastic properties accompanied with excellent biocompatibility and high corrosion resistance, we believe that this alloy is considered as a promising substitute for the biomedical materials containing Ni or other toxic elements., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Brominated flame retardants (BFRs), including polybrominated diphenyl ethers (PBDEs), tetrabromobisphenol A (TBBPA), and hexabromocyclododecanes (HBCDs), were investigated in bivalve (i.e., oyster (Crassostrea gigas) and mussel (Mytilus coruscus)), sediment, and seawater samples collected from aquaculture areas in South Korea to identify their occurrence, sources, and bioaccumulation. Among the studied chemicals, HBCDs predominated in bivalves and sediment, with concentrations of ND-67.52ng/g lipid weight and 3.47-168ng/g dry weight, respectively, while TBBPA was the highest contributor in seawater (ND-2.79ng/L). Compared with a non-aquaculture area, HBCD and PBDE concentrations were significantly higher in all matrices in the aquaculture area (Mann-Whitney U test, p<0.05), suggesting that sources may be located near or associated with the aquaculture areas, such as industrial complexes and expanded polystyrene buoys. Finally, the bioconcentration factor (BCF) and biota-sediment accumulation factor (BSAF) were estimated. Among the studied BFRs, BDE-47 (BCF: 1.70×10 6 L/kg; BSAF: 20.92) and α-HBCD (BCF: 1.05×10 6 L/kg; BSAF: 0.13) showed the highest accumulation potentials in bivalves., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The occurrence trends and effects of 30 human and veterinary pharmaceuticals, including antibiotics, anthelmintics, anti-inflammatory drugs, and β-blockers, in the marine environment, with a focus on seawater, sediment, cultured fish, and their feed collected from coastal and fish farm areas in the southern sea of Korea, were investigated. The concentrations of total pharmaceuticals in coastal area seawater (mean: 533ng/L) were higher than those in fish farm seawater (mean: 300ng/L), while the opposite trend (coastal area: 136ng/gdrywt

In this study a new superelastic Ti-18Zr-4.5Nb-3Sn-2Mo alloy was prepared by adding 2at% of Mo as a substitute for Nb to the Ti-18Zr-11Nb-3Sn alloy, and heat treatment at different temperatures was conducted. The temperature dependence of superelasticity and annealing texture was investigated. Texture showed a dependence of annealing temperature: the specimen annealed at 923K for 0.3ks exhibited {113} β <47¯1> β type texture which was similar to the deformation texture, while specimens annealed at 973, 1073K, and 1173K showed {001} β <110> β type recrystallization texture which was preferable for recovery strain. The largest recovery strain of 6.2%, which is the same level as that of the Ti-18Zr-11Nb-3Sn alloy, was obtained in the specimen annealed at 1173K for 0.3ks due to the well-developed {001} β <110> β type recrystallization texture. The Ti-18Zr-3Nb-3Sn-2Mo alloy presented a higher tensile strength compared with the Ti-18Zr-11Nb-3Sn alloy when heat treated at 1173K for 0.3ks, which was due to the solid solution strengthening effect of Mo. Annealing at 923K for 0.3ks was effective in obtaining a good combination of a high strength as 865MPa and a large recovery strain as 5.6%. The high recovery strain was due to the high stress at which the maximum recovery stain was obtained which was attributed to the small grain size formed at low annealing temperature., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Levels of 11 perfluoroalkyl acids (PFAAs), including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), were measured in wastewater (influent and effluent) and sludge samples collected from 25 industrial wastewater treatment plants (I-WWTPs) in five industrial sectors (chemicals, electronics, metals, paper, and textiles) in South Korea. The highest ∑11PFAAs concentrations were detected in the influent and effluent from the paper (median: 411ng/L) and textile (median: 106ng/L) industries, and PFOA and PFOS were the predominant PFAAs (49-66%) in wastewater. Exceptionally high levels of PFAAs were detected in the sludge associated with the electronics (median: 91.0ng/g) and chemical (median: 81.5ng/g) industries with PFOS being the predominant PFAA. The discharge loads of 11 PFAAs from I-WWTP were calculated that total discharge loads for the five industries were 0.146ton/yr. The textile industry had the highest discharge load with 0.055ton/yr (PFOA: 0.039ton/yr, PFOS: 0.010ton/yr). Municipal wastewater contributed more to the overall discharge of PFAAs (0.489ton/yr) due to the very small industrial wastewater discharge compared to municipal wastewater discharge, but the contribution of PFAAs from I-WWTPs cannot be ignored., (Copyright © 2016 Elsevier B.V. All rights reserved.)

We report cardiac arrest due to obstruction of the right ventricular outflow tract (RVOT) caused by an RVOT mass that was not identified preoperatively. A 62-year-old woman with renal cell carcinoma (RCC) experienced deteriorating hypotension and bradycardia during radical nephrectomy. Hemodynamic stability was maintained on extracorporeal membrane oxygenation, and after surgery, she was transferred to the intensive care unit. On postoperative day 3, transthoracic echocardiography showed an intracardiac mass obstructing the RVOT, which caused severe functional pulmonary stenosis and moderate resting pulmonary hypertension. Despite maintaining extracorporeal membrane oxygenation, the patient died of cardiac arrest. Our findings suggest that it may be necessary to perform additional tests if RCC has invaded the renal vein and inferior vena cava or if a patient with RCC has abnormal cardiovascular symptoms without definite etiology for exclusion of cardiac metastasis or tumor thrombus. In addition, intraoperative transesophageal echocardiography might be the procedure of choice for the evaluation of these conditions because other diagnostic tests are difficult to perform during surgery. In conclusion, for patients with acute hemodynamic instability for whom other possible causes have been excluded, we recommend that anesthesiologists use transesophageal echocardiography to detect outflow tract obstruction or pulmonary thromboembolism and perform anesthetic management., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Hepatitis C virus (HCV) is considered a major public health concern worldwide. Despite recent advances in curing chronic hepatitis C, unmet medical needs still remain, especially due to the high economic burden of therapies. Accordingly, our study aimed to identify affordable novel HCV inhibitors by screening of natural product compound libraries. We identified micrococcin P1, a macrocyclic peptide antibiotic, inhibiting HCV entry in a pan-genotypic manner with an EC50 range of 0.1-0.5 μM. Micrococcin P1 interfered with HCV entry at an attachment step. Furthermore, micrococcin P1 efficiently inhibited HCV spread by blocking cell-free infection as well as cell-to-cell transmission, without affecting the secretion of infectious virions. Interestingly, the putative molecular target of micrococcin P1 is glycoprotein E2 (IIe-630-Thr), as revealed by selection for viral drug resistance. In addition, micrococcin P1 inhibited sofosbuvir-resistant HCV strains and showed synergy in combination with selected HCV drugs, suggesting an alternative treatment paradigm for patients. In conclusion, we identified micrococcin P1 as specifically inhibiting entry of all HCV genotypes and demonstrated that micrococcin P1 potentially could add value to therapies in combination with current HCV interventions., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Study Objective: To compare analgesic efficacy of ultrasound (US) guidance alone and US guidance combined with nerve stimulation (NS) for continuous femoral nerve block (CFNB) in patients undergoing total knee arthroplasty (TKA)., Design: Prospective, randomized double-blind trial., Setting: Postanesthesia care unit and general ward., Patients: Fifty American Society of Anesthesiologist physical status I to II patients undergoing TKA under spinal anesthesia., Interventions: In group A (n = 25), an 18-gauge Tuohy needle was directed at the lower mid-part of the femoral nerve, and a nonstimulating catheter was inserted through the needle under US guidance. In group B (n = 25), an 18-gauge Tuohy needle and stimulating catheter were directed to the lower part of femoral nerve under US guidance, and quadriceps muscle contraction was checked using NS. All patients received a 20-mL loading dose of 0.2% ropivacaine, a continuous infusion of 4 mL/h, and a 4-mL bolus of 0.2% ropivacaine with a lockout time of 60 minutes for patient-controlled analgesia., Measurements: The primary outcome was resting and exercising pain quality assessed by numeric rating scale. Other outcomes included procedure time for correct catheter placement, block failure rate, patient satisfaction for postoperative pain control, total dose of local anesthetic, additional opioid requirement, and adverse effects postoperatively., Main Results: There were no significant differences between groups in resting and exercising numeric rating scale. Procedure times were longer in group B than group A (P < .05). There were no significant differences between groups in block failure rate or other outcomes., Conclusions: US-guided CFNB was associated with similar analgesic efficacy and block failure rate and reduced procedure time compared to US with NS guidance for CFNB in patients undergoing TKA., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Korea has kept the heritage of Korean traditional medicine (KM) during the 19th century harsh modernization, and has established a medical system in parallel with Western medicine. The purpose of this study was to review systematically the history and current system for educating highly qualified traditional medical doctors in Korea. KM produces 750 certified medical doctors every year with a 4-7-year curriculum in 12 universities and their affiliated hospitals. There are 22,074 clinicians along with 2474 clinical specialists in eight departments as of 2014. A national licensing examination and continuing medical education for KM are used for maintaining qualifications of KM doctors, and independent organizations are established for the evaluation of educational institutes. KM has thrived to establish an independent and competitive educational system for KM doctors, equivalent to Western medicine, and has regained a pivotal role for public health in Korea. This study would be useful for cultivating traditional medicine and establishing its educational system in the world.

Background and Aims: The pathogenesis of coronary artery disease (CAD) is closely associated with chronic inflammatory processes. CD8(+) T cells are a key participant in the pathogenesis of atherosclerosis, the major cause of CAD; however, it remains unclear which CD8(+) T-cell subset is responsible. We investigated the immunological features of CD8(+) T cells expressing low and high levels of the IL-6 receptor α chain (IL-6Rα), a cytokine known to play a key role in cardiovascular diseases., Methods: The expression of IL-6Rα on CD8(+) T cells and its association with plasma levels of soluble components of the IL-6/IL-6Rs as well as with clinical parameters were analyzed using FACS analysis and ELISA of CAD patients and age-matched healthy controls (HCs). Immunological characteristics of CD8(+) T cells expressing low and high levels of IL-6Rα (CD8(+)IL-6Rα(low or high)) were examined by in vitro culture and intracellular FACS analysis., Results: CAD patients had higher frequencies of circulating CD8(+)IL-6Rα(low) effector memory (EM) T cells compared with HCs (median frequency; 74.59% vs. 60.09%, p = 0.0158). Expanded CD8(+)IL-6Rα(low) T cells positively correlated with the frequency of senescent, cytotoxic CD8(+)CD57(+) T cells (r = 0.6655, p < 0.0001) and plasma IL-6 level (r = 0.3995, p = 0.0432) in CAD patients. Loss of IL-6Rα expression on CD8(+) T cells was induced by the combination of IL-6 and IL-15 with accompanying TCR-independent proliferation (p = 0.0101). Moreover, these CD8(+)IL-6Rα(low) T cells had features of type 1 cytotoxic CD8(+) T cells., Conclusions: Our findings suggest the possible involvement of expanded CD8(+)IL-6Rα(low) EM T cells in CAD through their pro-inflammatory and highly cytotoxic capacities., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Exposure to perfluoroalkyl substances (PFASs) may disrupt thyroid systems, though the specific effects of PFASs are still being elucidated. Since research regarding exposure in infants is highly limited, our goal was to investigate exposure levels of PFASs in infant serum and correlate these levels with thyroid hormones (THs). This was accomplished by analyzing 16 PFASs in sera from a case group of infants with congenital hypothyroidism and a control group. Total PFAS exposure level was 2.63-44.7ng/mL in the case group and 2.44-22.4ng/mL in the control group. Concentrations of serum perfluorooctanoic acid (PFOA, p<0.01), perfluorononanoic acid (PFNA, p<0.001), perfluorooctanoic acid (PFDA, p<0.005), and perfluoroundecanoic acid (PFUnDA, p<0.005) were significantly higher in the case group than the control group. Levels of certain PFASs (PFOA, perfluorotridecanoic acid [PFTrDA], and perfluorohexane sulfonate [PFHxS]) showed a moderate to weak correlation with relevant antibodies., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Upon screening synthetic small molecule libraries with the infectious hepatitis C virus (HCV) cell culture system, we identified a benzothiazepinecarboxamide (BTC) scaffold that inhibits HCV. A structure-activity relationship (SAR) study with BTCs was performed, and modifications that led to nanomolar antiviral activity and improved the selective index (CC50/EC50) by more than 1000-fold were identified. In addition, a pharmacophore modeling study determined that the tricyclic core and positive charge on the piperidine moiety were essential for antiviral activity. Furthermore, we demonstrated that BTC interferes with HCV glycoprotein E1/E2-mediated viral entry and the generation of infectious virions by using HCV pseudoparticle and cell culture supernatant transfer assays, respectively. BTC showed potent antiviral activity against HCV genotype 2 (EC50 = 0.01 ± 0.01 μM), but was less potent against a genotype 1/2 chimeric virus (EC50 = 2.71 ± 0.05 μM), which expressed the structural proteins of HCV genotype 1. In summary, we identified, optimized, and characterized novel BTC inhibitors that interfere with early and late steps of the HCV viral life cycle., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The adequate treatment of spinal cord injury (SCI)-induced neuropathic pain still remains an unresolved problem. The current medications predominantly used in the SCI-induced neuropathic pain therapy are morphine, anticonvulsants, antidepressants, and antiepileptics, which suggests that psychiatric aspects might be important factors in the treatment of neuropathic pain. It is well documented that the modulation of the sensory events is not a unique way for achieving pain relief. In addition, pain patients still express dissatisfaction and complain of unwanted effects of the medications, suggesting that alternative approaches for the treatment of neuropathic pain are essential. In psychiatry, pain relief represents relaxation and a feeling of comfort and satisfaction, which suggests that cognitive and emotional motivations are important factors in the treatment of neuropathic pain. The comorbidity of chronic pain and psychiatric disorders, which is well recognized, suggests that the effective therapeutic relief for neuropathic pain induced by SCI can be achieved in conjunction with the management of the sensory and psychiatric aspects of patient. In this review, we address the feasibility of a combined acupuncture and pharmacotherapy treatment for the relief of neuropathic pain behavior following SCI., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Reconstruction of branch pulmonary arteries (PAs) can be demanding in redo congenital cardiac surgeries. Sutureless patch angioplasty could be a useful method to solve this problem, and we evaluated the feasibility of sutureless patch angioplasty for postoperative PA stenosis in patients who underwent congenital cardiac surgery., Methods: We retrospectively reviewed 28 patients (19 males and 9 females) who underwent sutureless patch angioplasty for postoperative PA stenosis between November 2004 and April 2015. The median age was 7.3 months (range, 4.3 to 54.7), and the median weight was 7.2 kg (range, 5.3 to 12.2 kg). Right PA angioplasty was performed in 5, left PA angioplasty in 10, and both sides in 13 patients. The most common original diagnosis was hypoplastic left heart syndrome (n = 18 of 28, 64.3%). Concomitant surgeries were the bidirectional cavopulmonary shunt in 24 patients, the Fontan operation in 3, and the Rastelli operation in 1 patient., Results: No operative death occurred. However, 2 late deaths were recorded, and both were unrelated to PA angioplasty. Mean follow-up duration was 60.9 ± 33.1 months. None of the patients had postoperative bleeding or thrombotic occlusion. No reoperation for PA restenosis was performed, and only 1 patient (3.6%) had a PA balloon angioplasty with a good result 12.9 months after the operation. Echocardiography or computed tomography angiography at the recent follow-up showed good branch PAs in all patients., Conclusions: Sutureless patch angioplasty for postoperative PA stenosis could simplify PA angioplasty, and be a safe and effective method for PA reconstruction in patients who undergo congenital cardiac surgery., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: In tetralogy of Fallot, whether relieving right ventricular outflow tract obstruction requires transannular patch enlargement (TAPE) of the pulmonary valve depends on pulmonary valvular annulus size. The z-score of pulmonary annulus is most commonly used as a predictor of the need for TAPE. However, the z-score is a complex value affected by height, body weight, body surface area, and different reference populations. Therefore, we hypothesized that the great artery annulus size ratio (pulmonary valvular annulus size to aortic valve annuls size [GA ratio]) may be a better predictor of the need for TAPE., Methods: We analyzed 122 patients retrospectively who had undergone total correction of tetralogy of Fallot between January 2007 and March 2015. We categorized the patients into two groups, TAPE versus non-TAPE. Great arterial annuli sizes were evaluated in each group, and the GA ratio cutoff values for TAPE were calculated., Results: In total, 40 patients (32.8%) required TAPE. Both GA ratios and z-scores were smaller in the TAPE group than in the non-TAPE group (0.51 versus 0.67, p < 0.0001, and -2.46 versus -0.85, p < 0.0001, respectively). In receiver operating characteristics analyses, the z-score and GA ratio cutoff values were -1.67 (area under the curve = 0.797) and 0.56 (area under the curve = 0.900), respectively, demonstrating that the GA ratio was a more powerful diagnostic tool as a predictor of TAPE (p = 0.014)., Conclusions: Our results suggest that the GA ratio is a useful predictor for TAPE and can be applied readily and simply in clinical practice., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The occurrence and distribution of eight UV filters benzophenone (BP), benzophenone-3 (BP-3), ethylhexyl methoxy cinnamate (EHMC), 4-methylbenzylidene camphor (4-MBC), 2-ethylhexyl 4-dimethylaminobenzoate (OD-PABA), 2-ethylhexyl salicylate (EHS), isoamyl benzoate, and benzyl cinnamate in eleven sites among three rivers, five sewage treatment plants (STPs), and four wastewater treatment plants (WWTPs) located in different parts of Korea was investigated. The total concentrations of UV filters in the three sampled seasons were 62.9-412 ng L(-1) (river), 417-5055 ng L(-1) (STP influent), 108-2201 ng L(-1) (STP effluent), 122-4154 ng L(-1) (WWTP influent), and 120-849 ng L(-1) (WWTP effluent). The concentration of the target pollutants in the influent of the treatment systems was directly proportional to the resident population density. A seasonal increase of >27% was observed in the total concentration of the UV filters in the rivers and influents of the treatment plants (TPs) during summer. BP, BP-3, EHMC, 4-MBC, and EHS were the most dominant, showing a distinct distribution pattern that was dependent on the effectiveness of the treatment process and properties of each compound. The concentrations of the UV filters were higher in the TPs influents than in the rivers, and the most dominant UV filters in the rivers were those with low removal rate. Although biological treatment processes favored the removal of the UV filter compounds in the TPs, complete removal was not achieved before discharge into the rivers., (Copyright © 2015. Published by Elsevier B.V.)

Illicit drug consumption in five cities in South Korea was estimated by analyzing 17 drug residues in untreated wastewater samples collected during the Christmas and New Year period of 2012-13. Only methamphetamine, amphetamine, and codeine were detected at concentrations of tens of nanograms per liter or even lower concentrations in more than 90% of the samples. Other illicit drug residues (including cocaine, methadone, and benzoylecgonine) that have been detected frequently in wastewater from other countries were not found in this study. Methamphetamine was found to be the most widely used illicit drug in South Korea, and the estimated average consumption rate was 22 mg d(-1) (1000 people)(-1). This rate is, for example, 2-5 times lower than the estimated average consumption rates in Hong Kong and other parts of China and 4-80 times lower than the estimated average consumption rates in cities in Western countries. It should be noted that the wastewater samples analyzed in this study were collected during a holiday season, when daily consumption of illicit drugs is often higher than on an average day. The methamphetamine usage rates were calculated for different cities in South Korea, and the usage rates in smaller cities was higher (2-4 times) than the average., (Copyright © 2015. Published by Elsevier B.V.)

In this study, a new Ti-Zr-Nb-Sn alloy system was developed as Ni-free biomedical superelastic alloys with a large recovery strain and excellent biocompatibility. Ti-18Zr-(9-16)Nb-(0-4)Sn alloys were prepared by an Ar arc melting method and the effect of composition on the crystal structure and superelastic properties was investigated. A large superelastic recovery strain of 6.0% was observed in Ti-18Zr-12.5Nb-2Sn, Ti-18Zr-11Nb-3Sn, and Ti-18Zr-9.5Nb-4Sn alloys subjected to cold-rolling and solution treatment. XRD results showed that the large recovery strain of Sn-added alloys is due to a combination effect of a large transformation strain and a strong recrystallization texture. The Ti-18Zr-11Nb-3Sn alloy exhibited excellent cyclic stability with an extremely narrow stress hysteresis about 20MPa. Cytocompatibility was also examined using three types of cell lines, murine fibroblast L929, human osteosarcoma SaOS-2, and human umbilical vein endothelial cell HUVEC and the results showed that the Ti-18Zr-11Nb-3Sn alloy exhibited larger cell covering ratios when compared with those of the Ti-50.5Ni alloy for all kinds of cells., (Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

A new class of Ti-50Zr base biomedical superelastic alloys was developed in this study. The (Ti-Zr)-Mo-Sn alloys exhibited a shape memory effect and superelastic property by adjusting Mo and Sn contents. The (Ti-Zr)-1.5Mo-3Sn alloy revealed the most stable superelasticity among (Ti-Zr)-(1-2)Mo-(2-4)Sn alloys. The superelastic recovery strain showed a strong dependence on heat treatment temperature after cold working in the (Ti-Zr)-1.5Mo-3Sn alloy. The superelastic recovery strain increased as the heat treatment temperature increased although the critical stress for slip decreased. The (Ti-Zr)-1.5Mo-3Sn alloy heat treated at 1073K exhibited excellent superelastic properties with a large recovery strain as large as 7% which is due to the strong {001}β<110>β recrystallization texture., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Starch is one of the most abundant biopolymers in nature and is typically isolated from plants in the form of micro-scale granules. Recent studies reported that nano-scale starch particles could be readily prepared from starch granules, which have unique physical properties. Because starch is environmentally friendly, starch nanoparticles are suggested as one of the promising biomaterials for novel utilization in foods, cosmetics, medicines as well as various composites. An overview of the most up-to-date information regarding the starch nanoparticles including the preparation processes and physicochemical characterization will be presented in this review. Additionally, the prospects and outlooks for the industrial utilization of starch nanoparticles will be discussed., (Copyright © 2014 Elsevier B.V. All rights reserved.)

We aimed to verify the effectiveness of semi-permeable membrane devices (SPMDs) for monitoring hydrophobic organic compounds, such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), that are not easy to detect using conventional grab samples (because of their low concentrations), in water. We used SPMDs and grab samples to monitor PCBs and PBDEs upstream and downstream of a sewage treatment plant (STP) in the Suyeong River in Busan, Korea. Concentrations in three different phases (freely dissolved, apparently dissolved, and particulate) were measured, to investigate the aquatic fate of PCBs and PBDEs. The freely dissolved (SPMD) concentrations were 2-3 times higher than the apparently dissolved and particulate phase (grab sample) concentrations. No meaningful relationships were found between the total PCB and PBDE concentrations of the grab sample and SPMD sample because of the different partitioning behaviors and detection frequencies of the individual chemicals. However, the summed concentrations of specific PCB and PBDE congeners (that were abundant in all samples) in the grab and SPMD samples correlated well (r(2)=0.7451 for PCBs 28+52+153, r(2)=0.9987 for PBDEs 28+47+99). The PBDE concentrations measured using SPMDs decreased with increasing distance from the STP, but no apparent dilution effect was found in the grab samples. Our results show that SPMDs could be used to support grab sampling for specific chemicals, or to trace chemical sources (such as STPs) to the aquatic environment., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Serum samples were collected from volunteers of various ages and both genders using a proportionate stratified sampling method, to assess the exposure of the general population in Busan, South Korea to perfluorinated compounds (PFCs). 16 PFCs were investigated in serum samples from 306 adults (124 males and 182 females) and one day composite diet samples (breakfast, lunch, and dinner) from 20 of the serum donors, to investigate the relationship between food and serum PFC concentrations. Perfluorooctanoic acid and perfluorooctanesulfonic acid were the dominant PFCs in the serum samples, with mean concentrations of 8.4 and 13 ng/mL, respectively. Perfluorotridecanoic acid was the dominant PFC in the composite food samples, ranging from

Hepatitis C virus (HCV) infection is a global health concern with chronic liver damage threatening 3% of the world's population. To date, the standard of care is a combination of pegylated interferon-alpha with ribavirin, and recently two direct acting antivirals have entered the clinics. However, because of side effects, drug resistance and viral genotype-specific differences in efficacy current and potentially also future therapies have their limitations. Here, we describe the development of a phenotypic high-throughput assay to identify new cross-genotype inhibitors with novel mechanism of action, by combining a genotype (gt) 1 replicon with the infectious HCV gt2 cell culture system. To develop this phenotypic multiplex assay, HCV reporter cells expressing RFP-NLS-IPS and gt1b replicon cells expressing NS5A-GFP were co-plated and treated with compounds followed by inoculation with gt2a HCV. At 72h post treatment, RFP translocation as a marker for HCV infection and GFP fluorescence intensity as a marker for gt1 RNA replication were measured. Additionally, the total cell number, which serves as an indicator of cytotoxicity, was determined. This phenotypic strategy supports multi-parameter data acquisition from a single well to access cross-genotypic activity, provides an indication of the stage of the viral life cycle targeted, and also assesses compound cytotoxicity. Taken together, this multiplex phenotypic platform facilitates the identification of novel compounds for drug development and chemical probes for continuing efforts to understand the HCV life cycle., (Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.)

We investigated 33 pharmaceuticals and personal care products (PPCPs) with emphasis on anthelmintics and their metabolites in human sanitary waste treatment plants (HTPs), sewage treatment plants (STPs), hospital wastewater treatment plants (HWTPs), livestock wastewater treatment plants (LWTPs), river water and seawater. PPCPs showed the characteristic specific occurrence patterns according to wastewater sources. The LWTPs and HTPs showed higher levels (maximum 3000 times in influents) of anthelmintics than other wastewater treatment plants, indicating that livestock wastewater and human sanitary waste are one of principal sources of anthelmintics. Among anthelmintics, fenbendazole and its metabolites are relatively high in the LWTPs, while human anthelmintics such as albendazole and flubendazole are most dominant in the HTPs, STPs and HWTPs. The occurrence pattern of fenbendazole's metabolites in water was different from pharmacokinetics studies, showing the possibility of transformation mechanism other than the metabolism in animal bodies by some processes unknown to us. The river water and seawater are generally affected by the point sources, but the distribution patterns in some receiving water are slightly different from the effluent, indicating the influence of non-point sources., (Copyright © 2013 Elsevier B.V. All rights reserved.)

A combination of a radiotherapeutic regimen with telomerase inhibition is valuable when tumor cells are to be sensitized to radiation. Here, we describe cell clones unresponsive to radiosensitization after telomere shortening. After extensive division of individual transformed clones of mTERC-/- cells, about 22% of clones were unresponsive to radiosensitization even though telomerase action was inhibited. The telomere lengths of unsensitized mTERC-/- clones were reduced, as were those of most sensitized clones. However, the unsensitized clones did not exhibit chromosomal end-to-end fusion to the extent noted in all sensitized clones. Thus, a defense mechanism preventing telomere erosion is operative even when telomeres become shorter under conditions of telomerase deficiency, and results in unresponsiveness to the radiosensitization generally mediated by telomere shortening., (Copyright © 2010 Elsevier Inc. All rights reserved.)

We isolated spontaneously proliferating cells from primary astrocyte-enriched cultures prepared from neonatal rat brain. These cells proliferated and retained their characteristics for up to 50 generations. They expressed the microglial marker, OX42, but not glial fibrillary acidic protein, an astroglial marker. In addition, they possessed phagocytotic activity, and, when stimulated by lipopolysaccharide (LPS) or interferon-gamma (IFN-gamma), they expressed proinflammatory mediators, including cytokines (i.e., interleukin (IL)-1beta and tumor necrosis factor-alpha) and chemokines (i.e., IL-8 and monocyte chemotactic protein-1). Protein expression of inducible nitric oxide synthase and cyclooxygenase-2, and production of NO by these cells were induced by LPS or IFN-gamma. Thus, these cells possess the characteristics of microglia and can be used as a rat microglial cell line.