• 셀메드
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• 제10권1호
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• pp.7.1-7.6
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• 2020

Plants produce a wide range of active principles, making them a rich source of different types of medicines. Without any knowledge of the phytoconstituents or active principles the medicinal plants itself or in the form of polyherbal formulations, were used by all society of human being from ancient times for prevention and cure of disease, but most of the traditional formulations including the formulation of Ayurveda and Unani have not been scientifically validated in order to establish the pharmacopoeial standards to improve the efficacy. Globally, the people become conscious that uses of synthetic drugs for a long period is not safe; the trend of medical society at large is looking at alternatives from natural, safe sources to combat diseases. Due to this comprehension, it has been increased the demand for plant-derived medicine, and on the other side, it is extremely important to standardize the polyherbal formulations and validate them scientifically to improve their safety and efficacy. The polyherbal Unani formulation Safuf-e-Muallif is widely used and recommended in Unani system of medicine (USM) as a spermatogenic agent, semen thickening agent, etc. to treat sexual disorders viz. premature ejaculation, nocturnal emission, etc. The study mainly deals with phytochemical screening for the detection of nature of phytoconstituents and analytical technique like High-performance thin-layer chromatography (HPTLC) for developing fingerprint of Safuf-e-Muallif revealing specific identities of the drug. The phytochemical screening and HPTLC fingerprint profile for SM reported here may be used as a reference standard for quality control purpose in future.

• The Korean Journal of Physiology and Pharmacology
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• 제15권5호
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• pp.313-317
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• 2011

The effects of extremely low frequency electromagnetic fields (EMF) on intracellular $Ca^{2+}$ mobilization and cellular function in RBL 2H3 cells were investigated. Exposure to EMF (60 Hz, 0.1 or 1 mT) for 4 or 16 h did not produce any cytotoxic effects in RBL 2H3 cells. Melittin, ionomycin and thapsigargin each dose-dependently increased the intracellular $Ca^{2+}$ concentration. The increase of intracellular $Ca^{2+}$ induced by these three agents was not affected by exposure to EMF (60 Hz, 1 mT) for 4 or 16 h in RBL 2H3 cells. To investigate the effect of EMF on exocytosis, we measured beta-hexosaminidase release in RBL 2H3 cells. Basal release of beta-hexosaminidase was $12.3{\pm}2.3%$ in RBL 2H3 cells. Exposure to EMF (60 Hz, 0.1 or 1 mT) for 4 or 16 h did not affect the basal or $1{\mu}m$ melittin-induced beta-hexosaminidase release in RBL 2H3 cells. This study suggests that exposure to EMF (60 Hz, 0.1 or 1 mT), which is the limit of occupational exposure, has no influence on intracellular $Ca^{2+}$ mobilization and cellular function in RBL 2H3 cells.

• The Korean Journal of Physiology and Pharmacology
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• 제24권6호
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• pp.463-472
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• 2020

Direct reprogramming, also known as a trans-differentiation, is a technique to allow mature cells to be converted into other types of cells without inducing a pluripotent stage. It has been suggested as a major strategy to acquire the desired type of cells in cell-based therapies to repair damaged tissues. Studies related to switching the fate of cells through epigenetic modification have been progressing and they can bypass safety issues raised by the virus-based transfection methods. In this study, a protocol was established to directly convert fully differentiated fibroblasts into diverse mesenchymal-lineage cells, such as osteoblasts, adipocytes, chondrocytes, and ectodermal cells, including neurons, by means of DNA demethylation, immediately followed by culturing in various differentiating media. First, 24 h exposure of 5-azacytidine (5-aza-CN), a well-characterized DNA methyl transferase inhibitor, to NIH-3T3 murine fibroblast cells induced the expression of stem-cell markers, that is, increasing cell plasticity. Next, 5-aza-CN treated fibroblasts were cultured in osteogenic, adipogenic, chondrogenic, and neurogenic media with or without bone morphogenetic protein 2 for a designated period. Differentiation of each desired type of cell was verified by quantitative reverse transcriptase-polymerase chain reaction/western blot assays for appropriate marker expression and by various staining methods, such as alkaline phosphatase/alizarin red S/oil red O/alcian blue. These proposed procedures allowed easier acquisition of the desired cells without any transgenic modification, using direct reprogramming technology, and thus may help make it more available in the clinical fields of regenerative medicine.

• The Korean Journal of Physiology and Pharmacology
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• 제24권6호
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• pp.441-452
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• 2020

In vivo animal models are limited in their ability to mimic the extremely complex systems of the human body, and there is increasing disquiet about the ethics of animal research. Many authorities in different geographical areas are considering implementing a ban on animal testing, including testing for cosmetics and pharmaceuticals. Therefore, there is a need for research into systems that can replicate the responses of laboratory animals and simulate environments similar to the human body in a laboratory. An in vitro two-dimensional cell culture model is widely used, because such a system is relatively inexpensive, easy to implement, and can gather considerable amounts of reference data. However, these models lack a real physiological extracellular environment. Recent advances in stem cell biology, tissue engineering, and microfabrication techniques have facilitated the development of various 3D cell culture models. These include multicellular spheroids, organoids, and organs-on-chips, each of which has its own advantages and limitations. Organoids are organ-specific cell clusters created by aggregating cells derived from pluripotent, adult, and cancer stem cells. Patient-derived organoids can be used as models of human disease in a culture dish. Biomimetic organ chips are models that replicate the physiological and mechanical functions of human organs. Many organoids and organ-on-a-chips have been developed for drug screening and testing, so competition for patents between countries is also intensifying. We analyzed the scientific and technological trends underlying these cutting-edge models, which are developed for use as non-animal models for testing safety and efficacy at the nonclinical stages of drug development.

• Biomolecules & Therapeutics
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• 제3권4호
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• pp.322-326
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• 1995

General pharmacology of LB20304, a quinolone antibiotic, were examined in terms of general behaviour, cardiovascular, and central nervous system. LB20304 at oral dose of 2,000 mg/kg did not induce significant behavioural changes in mice. In contrast with ciprofloxacin, LB20304 at dose of 20 mg/kg, iv. did not show any observable effects on the blood pressure in rats. Displacement of [$^3$H]muscimol binding to the rat brain synaptic membranes was measured. LB20304 was shown to be about five times less potent than ciprofloxacin in specific GABA receptor binding. Drug interaction between LB20304 and 4-biphenyl acetic acid, an active metabolite of fenbufen, was assessed in mice by measuring convulsion and/or subsequent death. A single oral pretreatment with 4-BPA at 400 mg/kg increased the incidence of convulsion and death after oral administration of ciprofloxacin at the doses of 25, 50, and 100 from zero of five to three of five, two of five, and four of five, respectively, whereas LB20304 alone or combination with 4-BPA caused neither convulsions nor death at the doses of 12.5, 25, 50, and 100 mg/kg, respectively. Quinolones-induced epileptogenic activities were assessed by a direct intracerebral injection of test articles. The CD$_{50}$ values (nmole) are as follows; 169.47, 35.36, 105.29, and 88.67 for LB20304, ciprofloxacin, of loxacin, and lomefloxacin, respectively. From these data, LB 20304 at therapeutic doses seems to be much more safe than any other quinolones tested.d.

• The Korean Journal of Physiology and Pharmacology
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• 제23권5호
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• pp.393-402
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• 2019

Aurora kinases inhibitors, including ZM447439 (ZM), which suppress cell division, have attracted a great deal of attention as potential novel anti-cancer drugs. Several recent studies have confirmed the anti-cancer effects of ZM in various cancer cell lines. However, there have been no studies regarding the cardiac safety of this agent. We performed several cytotoxicity, invasion and migration assays to examine the anti-cancer effects of ZM. To evaluate the potential effects of ZM on cardiac repolarisation, whole-cell patch-clamp experiments were performed with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and cells with heterogeneous cardiac ion channel expression. We also conducted a contractility assay with rat ventricular myocytes to determine the effects of ZM on myocardial contraction and/or relaxation. In tests to determine in vitro efficacy, ZM inhibited the proliferation of A549, H1299 (lung cancer), MCF-7 (breast cancer) and HepG2 (hepatoma) cell lines with $IC_{50}$ in the submicromolar range, and attenuated the invasive and metastatic capacity of A549 cells. In cardiac toxicity testing, ZM did not significantly affect $I_{Na}$, $I_{Ks}$ or $I_{K1}$, but decreased $I_{hERG}$ in a dose-dependent manner ($IC_{50}$: $6.53{\mu}M$). In action potential (AP) assay using hiPSC-CMs, ZM did not induce any changes in AP parameters up to $3{\mu}M$, but it at $10{\mu}M$ induced prolongation of AP duration. In summary, ZM showed potent broad-spectrum anti-tumor activity, but relatively low levels of cardiac side effects compared to the effective doses to tumor. Therefore, ZM has a potential to be a candidate as an anti-cancer with low cardiac toxicity.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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• pp.84-84
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• 2001

The heartwood of Rhus verniciflua has been known to be effective for lingering intoxication and diabetes mellitus and rheumatoidal arthritis in traditional folk medicine in Korea. We have previously reported that antimutagenic effect of flavonoids derived from the heartwood extract of R. verniciflua, and sulfuretin was the active component. Recently, we have demonstrated that sulfuretin could be an anti-inflammatory principle of the R. verniciflua heartwood partially dependent on cyclooxigenase-inhibitory activity. The present study was undertaken to demonstrate the anti-rheumatoidal arthritis effect of the R. verniciflua heartwood extract, its EtOAc fraction and the main flavonoids, sulfuretin and fustin. All the test samples showed variably significant inhibitory effects on hind paw edema induced by Freund's complete adjuvant reagent (FCA reagent). Sulfuretin treatment with 10 mg/kg (i.p.) for seven days showed the inhibitory effect of 54.2${\pm}$3.0%, Similar trends in RA- and CRP tests, vascular permeability test and trypsin inhibitor test were also found. In addition, no dead mouse was found even when the dose was increased up to 5,000 mg/kg (i.p.). Treatment with 250-1,500 mg/kg on normal rats did not show any marked toxicological significances in the tests of body weight gain, wet weight of organs and hepatic functions. These results suggested that the heartwood of R. verniciflua could be an adequate crude drug for rheumatoidal arthritis with an active component of sulfuretin. The toxicological safety of the heartwood of R, verniciflua is contrasted to known severe allergenic action of the stem bark or its exudate.

• Biomolecules & Therapeutics
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• 제17권4호
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• pp.438-445
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• 2009

We investigated global gene expression from both mouse liver and mouse hepatic cell lines treated with acetaminophen (APAP) in order to compare in vivo and in vitro profiles and to assess the feasibility of the two systems. During our analyses of gene expression profiles, we picked up several down-regulated genes, such as the cytochrome P450 family 51 (Cyp51), sulfotransferase family cytosolic 1C member 2 (Sult1c2), 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (Hmgcs1), and several genes that were up-regulated by APAP, such as growth arrest and DNA-damage-inducible 45 alpha (Gadd45a), transformation related protein 53 inducible nuclear protein 1 (Trp53inp1) and zinc finger protein 688 (Zfp688). For validation of gene function, synthesized short interfering RNAs (siRNAs) for these genes were transfected in a mouse hepatic cell line, BNL CL.2, for investigation of cell viability and mRNA expression level. We found that siRNA transfection of these genes induced down-regulation of respective mRNA expression and decreased cell viability. siRNA transfection for Cyp51 and others induced morphological alterations, such as membrane thickening and nuclear condensation. Taken together, siRNA transfection of these six genes decreased cell viability and induced alteration in cellular morphology, along with effective inhibition of respective mRNA, suggesting that these genes could be associated with APAP-induced toxicity. Furthermore, these genes may be used in the investigation of hepatotoxicity, for better understanding of its mechanism.

• Biomolecules & Therapeutics
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• 제28권2호
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• pp.163-171
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• 2020

Silibinin exhibits antidiabetic potential by preserving the mass and function of pancreatic β-cells through up-regulation of estrogen receptor-α (ERα) expression. However, the underlying protective mechanism of silibinin in pancreatic β-cells is still unclear. In the current study, we sought to determine whether ERα acts as the target of silibinin for the modulation of antioxidative response in pancreatic β-cells under high glucose and high fat conditions. Our in vivo study revealed that a 4-week oral administration of silibinin (100 mg/kg/day) decreased fasting blood glucose with a concurrent increase in levels of serum insulin in high-fat diet/streptozotocin-induced type 2 diabetic rats. Moreover, expression of ERα, NF-E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in pancreatic β-cells in pancreatic islets was increased by silibinin treatment. Accordingly, silibinin (10 μM) elevated viability, insulin biosynthesis, and insulin secretion of high glucose/palmitate-treated INS-1 cells accompanied by increased expression of ERα, Nrf2, and HO-1 as well as decreased reactive oxygen species production in vitro. Treatment using an ERα antagonist (MPP) in INS-1 cells or silencing ERα expression in INS-1 and NIT-1 cells with siRNA abolished the protective effects of silibinin. Our study suggests that silibinin activates the Nrf2-antioxidative pathways in pancreatic β-cells through regulation of ERα expression.

• Safety and Health at Work
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• 제2권4호
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• pp.301-312
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• 2011

Firefighters and police officers have the third highest prevalence of obesity among 41 male occupational groups in the United States (US). However, few studies have examined the relationship of firefighter working conditions and health behaviors with obesity. This paper presents a theoretical framework describing the relationship between working conditions, health behaviors, and obesity in firefighters. In addition, the paper describes a detailed study plan for exploring the role of occupational and behavioral risk factors in the development of obesity in firefighters enrolled in the Orange County Fire Authority Wellness Fitness Program. The study plan will be described with emphasis on its methodological merits: adopting a participatory action research approach, developing a firefighter-specific work and health questionnaire, conducting both a cross-sectional epidemiological study using the questionnaire and a sub-study to assess the validity of the questionnaire with dietary intake and physical activity measures, and evaluating the strengths and weaknesses of the body mass index as an obesity measure in comparison to skinfold-based percent body fat. The study plan based on a theoretical framework can be an essential first step for establishing effective intervention programs for obesity among professional and voluntary firefighters.