• Journal of Life Science
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• v.31 no.11
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• pp.1037-1045
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• 2021

The prevalence of obesity is increasing worldwide, and since obesity is associated with dietary factors and sedentary lifestyles, it is a disease that is readily developing in the modern population. Because obesity is accompanied by serious complications such as diabetes and cardiovascular disease, prevention and treatment are important. Currently, drugs such as liraglutide and phentermine are used to treat obesity by suppressing appetite and inducing gastrointestinal motility delay. However, various side effects may occur, including thyroid cancer, cardiovascular problems, and central nervous system disorders. Therefore, to explore an obesity treatment method with relatively few side effects, a method known as "fat browning" was introduced to change white adipose tissue into brown adipose tissue to increase energy consumption. Ongoing studies are attempting to find effective natural substances to safely induce browning. Many natural substances have been identified. The induction of browning by treatment with natural substances generally involves three mechanisms: positive control of browning-inducing factors, inhibition of differentiation into white adipose tissue, and the activation of mechanisms related to browning. In this study, we describe plant extracts with known browning-inducing effects, such as strawberry, black raspberry, cinnamomum cassia, and Ecklonia stolonifera extracts. We also summarize the underlying mechanisms of action identified thus far, including the signaling pathway mediated by these extracts to induce browning. Furthermore, the effects of brown adipose tissue generated through browning on heart disease as an endocrine organ disruptor are discussed.

• Journal of Food Hygiene and Safety
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• v.22 no.1
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• pp.1-14
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• 2007

The term, "food safety", has traditionally been viewed as a practical science aimed at assuring the prevention acute illnesses caused by biological microorganisms, and only to a minor extent, chronic diseases cause by chronic low level exposures to natural and synthetic chemicals or pollutants. "food safety" meant to prevent microbiological agents/toxins in/on foods, due to contamination any where from "farm to Fork", from causing acute health effects, especially to the young, immune-compromised, genetically-predisposed and elderly. However, today a broader view must also include the fact that diet, perse (nutrients, vitamins/minerals, calories), as well as low level toxins and pollutant or supplemented synthetic chemicals, can alter gene expressions of stem/progenitor/terminally-differentiated cells, leading to chronic inflammation and other mal-functions that could lead to diseases such as cancer, diabetes, atherogenesis and possibly reproductive and neurological disorders. Understanding of the mechanisms by which natural or synthetic chemical toxins/toxicants, in/on food, interact with the pathogenesis of acute and chronic diseases, should lead to a "systems" approach to "food safety". Clearly, the interactions of diet/food with the genetic background, gender, and developmental state of the individual, together with (a) interactions of other endogenous/exogenous chemicals/drugs; (b) the specific biology of the cells being affected; (c) the mechanisms by which the presence or absence of toxins/toxicants and nutrients work to cause toxicities; and (d) how those mechanisms affect the pathogenesis of acute and/or chronic diseases, must be integrated into a "system" approach. Mechanisms of how toxins/toxicants cause cellular toxicities, such as mutagenesis; cytotoxicity and altered gene expression, must take into account (a) irreversible or reversal changes caused by these toxins or toxicants; (b)concepts of thresholds or no-thresholds of action; and (c) concepts of differential effects on stem cells, progenitor cells and terminally differentiated cells in different organs. This brief Commentary tries to illustrate this complex interaction between what is on/in foods with one disease, namely cancer. Since the understanding of cancer, while still incomplete, can shed light on the multiple ways that toxins/toxicants, as well as dietary modulation of nutrients/vitamins/metals/ calories, can either enhance or reduce the risk to cancer. In particular, diets that alter the embryo-fetal micro-environment might dramatically alter disease formation later in life. In effect "food safety" can not be assessed without understanding how food could be 'toxic', or how that mechanism of toxicity interacts with the pathogenesis of any disease.

• The Korean Journal of Pain
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• v.27 no.1
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• pp.54-62
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• 2014

Background: The recently known analgesic action mechanisms of nefopam (NFP) are similar to those of anticonvulsants and antidepressants in neuropathic pain treatment. It is difficult to prescribe high doses of oral neuropathic drugs without titration due to adverse effects. Unfortunately, there are few available intravenous analgesics for the immediate management of acute flare-ups of the chronic neuropathic pain. The aim of this study was to determine the additional analgesic effects for neuropathic pain of NFP and its adverse effects during the titration of oral medications for neuropathic pain among inpatients with postherpetic neuralgia (PHN). Methods: Eighty inpatients with PHN were randomly divided into either the NFP or normal saline (NS) groups. Each patient received a 3-day intravenous continuous infusion of either NFP with a consecutive dose reduction of 60, 40, and 20 mg/d, or NS simultaneously while dose titrations of oral medications for neuropathic pain gradually increased every 3 days. The efficacy of additional NFP was evaluated by using the neuropathic pain symptom inventory (NPSI) score for 12 days. Adverse effects were also recorded. Results: The median NPSI score was significantly lower in the NFP group from days 1 to 6 of hospitalization. The representative alleviating symptoms of pain after using NFP were both spontaneous and evoked neuropathic pain. Reported common adverse effects were nausea, dizziness, and somnolence, in order of frequency. Conclusions: An intravenous continuous infusion of NFP reduces spontaneous and evoked neuropathic pain with tolerable adverse effects during the titration of oral medications in inpatients with PHN.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2503-2508
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• 2013

Histone deacetylation mediated by histone deacetylases (HDACs) has been reported as one of the epigenetic mechanisms associated with tumorigenesis. The poor responsiveness of anticancer drugs found with cholangiocarcinoma (CCA) leads to short survival rate. We aimed to investigate mRNA expression of HDACs class I and II, and the effect of HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA), in CCA in vitro. Expression of HDACs was studied in CCA cell lines (M213, M214 and KKU-100) and an immortal cholangiocyte (MMNK1) by semi-quantitative reverse transcription-PCR. SAHA and VPA, as well as a classical chemotherapeutic drug 5 -fluorouacil (5-FU) were used in this study. Cell proliferation was determined by sulforhodamine assay. $IC_{50}$ and $IC_{20}$ were then analyzed for each agent and cell line. Moreover, synergistic potentional of VPA or SAHA in combination with 5-FU at sub toxic does ($IC_{20}$) of each agent was also evaluated. Statistic difference of HDACs expression or cell proliferation in each experimental condition was analyzed by Student's t-test. The result demonstrated that HDACs were expressed in all studied cell types. Both SAHA and VPA inhibited cell proliferation in a dose-dependent manner. Interestingly, KKU-100 which was less senstitive to classical chemotheraoeutic 5-FU was highly was sensitive to HDAC inhibitors. Simultaneous combination of subtoxic doses of HDAC inhibitors and 5-FU signiicantly inhibited cell proliferation in CCA cell lines compared to single sgent treatment($P{\leq}0.01$), while sequentially combined treatments were less effective. The present study showed inhibitory effects of HDACIs on cell proliferation in CCA cell lines, with synergistic antitumor potential demonstrated by simultaneous combination of VPA or SAHA with 5-FU, suggesting a novel alternative therapeutic strategy in effective treatment of CCA.

• Journal of The Korean Society of Clinical Toxicology
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• v.8 no.2
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• pp.113-121
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• 2010

Purpose: Drug-induced non-cardiogenic pulmonary edema has been reported on in a drug case series. For most of the agents that cause pulmonary edema, the pathogenic mechanisms that are responsible for the pulmonary edema remain unknown. We report here on the cases of suspected drug-induced pulmonary edema and we analyze the clinical characteristics. Methods: We reviewed the medical records of 1,345 patients who had drug adverse effects and drug poisoning from January 2005 to July 2010, and 480 of these patients were admitted to the EM Department. Among them, 17 patients developed abnormal chest radiological findings and they were analyzed for any clinical characteristics, the initial symptoms, securing the airway and the clinical results. Results: Seventeen patients out of 480 (3.54%) developed drug-induced abnormal chest radiographic pulmonary edema; they displayed initial symptoms that included mental change (41.2%), dyspnea (17.6%), vomiting (11.8%), etc, and some displayed no symptoms at all (11.8%). Only 3 patients out of the 11 who died or had severe pulmonary edema were able to obtain an advanced airway prior to their arrival to the EM Department. Clinical recovery was generally rapid and this was mostly completed within 6 hours. The mortality rate was 11.8% (2 of 17 patients), and the causative drugs were found to be propofol (35.3%, 6 of 17 patients), multiple drugs (41.2% or 7 out of 17) and one patient each with ephedrine, ethylene glycol, doxylamine and an unknown drug, respectively. Conclusion: Drug-induced pulmonary edema and deaths are not uncommon, and recovery is typically rapid with few long-term sequelae when drug administration is discontinued. Oxygen therapy and securing the airway must be performed during transportation for patients with pulmonary edema.

• Interdisciplinary Bio Central
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• v.5 no.2
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• pp.3.1-3.7
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• 2013

Recently, the productivity of drug discovery has gradually decreased as the limitations of single-target-based drugs for various and complex diseases become exposed. To overcome these limitations, drug combinations have been proposed, and great efforts have been made to predict efficacious drug combinations by statistical methods using drug databases. However, previous methods which did not take into account biological networks are insufficient for elaborate predictions. Also, increased evidences to support the fact that drug effects are closely related to metabolic enzymes suggested the possibility for a new approach to the study drug combinations. Therefore, in this paper we suggest a novel approach for analyzing drug combinations using a metabolic network in a systematic manner. The influence of a drug on the metabolic network is described using the distance between the drug target and an enzyme. Target-enzyme distances are converted into influence scores, and from these scores we calculated the correlations between drugs. The result shows that the influence score derived from the targetenzyme distance reflects the mechanism of drug action onto the metabolic network properly. In an analysis of the correlation score distribution, efficacious drug combinations tended to have low correlation scores, and this tendency corresponded to the known properties of the drug combinations. These facts suggest that our approach is useful for prediction drug combinations with an advanced understanding of drug mechanisms.

• The Korean Journal of Pharmacology
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• v.8 no.2
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• pp.35-39
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• 1972

Previous studies on the effect of the visible lights on the organism have shown the possible influences on the nervous system. It was reported that the illumination of blue beam increased the sympathetic tone and that of red beam increased the parasympathetic tone. The pharmacological actions of the sympathomimetics were also known to be altered by various visible lights. But their modes and mechanisms of actions on the nervous system have not been clarified and is obscure. To elucidate the precise mechanism of action of the visible lights on the nervous system, present study was made to observe the survival time of the mole living in the dark environment, under the illumination of the various visible lights and influences of several drugs. The results are summerized as follows: 1. The illumination of the natural sun light caused the survival time of the mole to be shortened and visible monochromatic beams (red, blue and green) even more markedly shortened the survival time. No significant difference was noted depending on the wave length of the chromatic beam. 2. The shortened survival time caused by the visible monochromatic lights was prolonged by strychnine but not affected by morphine. 3. The survival time under the illumination of the visible monochromatic lights was prolonged by acetylcholine and physostigmine. 4. The shortened survival time under the illumination of the monochromatic visible lights was not affected by adrenaline but prolonged by priscoline. It is suggested that the shortened survival time of the mole by the illumination of the visible lights can be prolonged by the stimulation of central and parasympathetic nervous system and blocking of the sympathetic nervous system.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.517-535
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• 2014

Poly (lactic-co-glycolic acid) (PLGA) is one of the most effective biodegradable polymeric nanoparticles (NPs). It has been approved by the US FDA to use in drug delivery systems due to controlled and sustained-release properties, low toxicity, and biocompatibility with tissue and cells. In the present review, the structure and properties of PLGA copolymers synthesized by ring-opening polymerization of DL-lactide and glicolide were characterized using 1H nuclear magnetic resonance spectroscopy, gel permeation chromatography, Fourier transform infrared spectroscopy and differential scanning calorimetry. Methods of preparation and characterization, various surface modifications, encapsulation of diverse anticancer drugs, active or passive tumor targeting and different release mechanisms of PLGA nanoparticles are discussed. Increasing experience in the application of PLGA nanoparticles has provided a promising future for use of these nanoparticles in cancer treatment, with high efficacy and few side effects.

• Journal of Ginseng Research
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• v.47 no.4
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• pp.583-592
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• 2023

Background: Alcohol is one of the most commonly used psychoactive drugs. Due to its addictive characteristics, many people struggle with the side effects of alcohol. Korean Red Ginseng (KRG) is a traditional herbal medicine that is widely used to treat various health problems. However, the effects and mechanisms of KRG in alcohol-induced responses remain unclear. Therefore, the purpose of this study was to investigate the effects of KRG in alcohol-induced responses. Methods: We investigated two aspects: alcohol-induced addictive responses and spatial working memory impairments. To determine the effects of KRG in alcohol-induced addictive responses, we performed conditioned place preference tests and withdrawal symptom observations. To assess the effects of KRG in alcohol-induced spatial working memory impairment, Y-maze, Barnes maze, and novel object recognition tests were performed using mice after repeated alcohol and KRG exposure. To investigate the potential mechanism of KRG activity, gas chromatography-mass spectrometry and western blot analysis were performed. Results: KRG-treated mice showed dose-dependent restoration of impaired spatial working memory following repeated alcohol exposure. Furthermore, withdrawal symptoms to alcohol were reduced in mice treated with KRG and alcohol. The PKA-CREB signaling pathway was activated after alcohol administration, which was reduced by KRG. However, the levels of inflammatory cytokines were increased by alcohol and decreased by KRG. Conclusion: Taken together, KRG may alleviate alcohol-induced spatial working memory impairments and addictive responses through anti-neuroinflammatory activity rather than through the PKA-CREB signaling pathway.

• Biomolecules & Therapeutics
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• v.15 no.3
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• pp.145-149
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• 2007

We have previously shown that 2,4,3',5'-tetramethoxystilbene (TMS), a synthetic trans-stilbene analogue acting as a potent inhibitor of human cytochrome P450 1B1, induces apoptotic cell death in human cancer cells. In the present studies, we report the mechanisms of apoptotic cell death by TMS in human promyelocytic leukemic HL-60 cells. We found that treatment of HL-60 cells with TMS suppressed the cell growth in a concentration-dependent manner with $IC_{50}$ value of about 0.8 ${\mu}M$. Immunoblot experiments revealed that DMHS-induced apoptosis was associated with cleavage of poly (ADP-ribose) polymerase. The release of cytochrome c from mitochondria into the cytosol was significantly increased in response to TMS. TMS caused activation of caspase-3 in a concentration-dependent manner and TMS-mediated caspase-3 activation was partially prevented by the caspase inhibitor, zVAD-fmk. Interestingly, we found that the cytotoxic effect of anticancer drugs such as paclitaxel, docetaxel, or etoposide was enhanced in the presence of TMS. Simultaneous treatment with TCDD also significantly increased cytotoxic effects of TMS alone or TMS and anti-cancer agents. Taken together, our present results indicated that TMS leads to apoptotic cell death in HL-60 cells through activation of caspase-3 activity and release of cytochrome c into cytosol. The ability of TMS to increase cytotoxic effect of anticancer drugs may contribute to its usefulness for cancer chemotherapy.