• Title/Summary/Keyword: PDE5

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Udenafil Induces the Hair Growth Effect of Adipose-Derived Stem Cells

  • Choi, Nahyun;Sung, Jong-Hyuk
    • Biomolecules & Therapeutics
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    • v.27 no.4
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    • pp.404-413
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    • 2019
  • Udenafil, which is a $PDE_5$ inhibitor, is used to treat erectile dysfunction. However, it is unclear whether udenafil induces hair growth via the stimulation of adipose-derived stem cells (ASCs). In this study, we investigated whether udenafil stimulates ASCs and whether increased growth factor secretion from ASCs to facilitate hair growth. We found that subcutaneous injection of udenafiltreated ASCs accelerated telogen-to-anagen transition in vivo. We also observed that udenafil induced proliferation, migration and tube formation of ASCs. It also increased the secretion of growth factors from ASCs, such as interleukin-4 (IL-4) and IL12B, and the phosphorylation of ERK1/2 and $NF{\kappa}B$. Furthermore, concomitant upregulation of IL-4 and IL12B mRNA levels was attenuated by ERK inhibitor or $NF{\kappa}B$ knockdown. Application of IL-4 or IL12B enhanced anagen induction in mice and increased hair follicle length in organ culture. The results indicated that udenafil stimulates ASC motility and increases paracrine growth factor, including cytokine signaling. Udenafil-stimulated secretion of cytokine from ASCs may promote hair growth via the ERK and $NF{\kappa}B$ pathways. Therefore, udenafil can be used as an ASC-preconditioning agent for hair growth.

Synthesis of Methoxy Polyoxyethlene Dodecanoates (Methoxy Polyoxyethylene Dodecanoate의 합성)

  • Kang, Yun-Seog;Noh, Sueng-Ho;Choi, Seung-Ok;Nam, Ki-Dae
    • Applied Chemistry for Engineering
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    • v.9 no.5
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    • pp.749-753
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    • 1998
  • Methoxy polyoxyethylene dodecanoates, kinds of nonionic surfactants, could be obtained from addition of ethylene oxide (5, 7, 9, and 12mol) with fatty acid methyl ester utilizing solid catalyst, metal oxide. Because ethylene oxide (EO) couldn't react directly in acid or alkali catalyst with dodecanoic acid methyl ester (DME) that had no active hydrogen, the reaction to add EO was carried out using active solid catalyst. By using IR, HPLC and $^1H$ NMR analysis, structural confirmation of methyl polyoxy ethylene dodecanate showed high yield ranging from 93 to 97%. EO unit mol number of reacted products was 5.2, 7.1, 9.2 and 12.1 mol respectively. Also, EO adduct distrobution of ethoxylated methyl laurate (MPD) had normal distribution curve like polyoxyethylene alkyl ether (AE).

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Status Analysis of Adulterated Herbal Medicine (국내외 위변조 한약 현황 분석)

  • Lee, Soojin
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.34 no.5
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    • pp.215-221
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    • 2020
  • Adulterated herbal medicine is intentionally added with undeclared improper or inferior ingredients which should not be in herbal medicine. The contamination with potentially hazardous substances such as heavy metal, pesticides, fungus, and microorganism sometimes can be regarded as one of adulteration in a broad sense. The problem of adulteration is that adulterated herbal medicine shows poor quality and/or can cause adverse events. Therefore, it is important to control adulteration issues for quality assurance and qualitative improvement of herbal medicines. This study aims to summarize and make a reference how to control adulterated herbal medicine. In this process, this study is to investigate studies about adulterated herbal medicine via searching Korean and foreign electronic databases such as PubMed, NDSL and OASIS. Finally eighteen papers were included to this study and analyzed according to the type of study, the category and efficacy of adulterants, the type of analysis methodologies and possible adverse events of adulterants. Phosphodiesterase type 5 (PDE-5) inhibitors for male sexual enhancement and anorexic, laxative, diuretic agents for weight loss and treating obesity has been used frequently as adulterants. The range of adverse event caused by adulterated herbal medicine were very wide from mild symptoms such as diarrhea, constipation, dizziness and blurred vision to very severe symptoms such as heart failure, hypoglycemia and renal impairment. This study showed the recent trend on the research of adulterated herbal medicine and this will be the ground to develop more detailed systems to control adulterated herbal medicine.

The Effects of Woohwangcheongsim-won on Hypoxic E18 Cortical Neuroblast (우황청심원(牛黃淸心元)이 저산소증 유발 배양신경세포에 미치는 영향)

  • Cho, Gyu-Seon;Shin, Gil-Cho;Moon, Il-Soo;Lee, Won-Chul;Chung, Sung-Hyun
    • The Journal of Internal Korean Medicine
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    • v.22 no.2
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    • pp.135-144
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    • 2001
  • Objectives : The purpose of this investigation is to evaluate the effects of Woohwangcheongsim-won on neuronal death of hypoxic E18 cortical neuroblast. Methods : To evaluate the effect of Woohwangcheongsim-won on neuronal death caused by hypoxia, the survival rate of E18 cortical neuroblast was measured with MTT assay and the changes of several synaptic proteins and enzymes were investigated with the immunoblot assays. Results : The E18 cortical neuroblasts were added 50, 100, 500, 1,000, and $5,000{\mu}g/ml$ Woohwangcheongsim-won. They showed neurotoxicity, when the concentration of Woohwangcheongsim-won was above $1,000{\mu}g/ml$. The E18 cortical neuroblasts, which were added 50, 100, and $500{\mu}g/ml$ Woohwangcheongsim-won, were exposed 98% $N_2/5%\;CO_2$ for 3 hours to induce hypoxia, 3 days later, the survival rate of $50{\mu}g/ml$ Woohwangcheongsim-won was 141.5% when compared to the control group. On the immuneblot assays, the expressions of ${\alpha}$CaMKII, NR2A, NR28, PDE2, PSD-95, and eEF-$1{\alpha}$ were increased in normoxia, but those of NR2A, NR2B were decreased in hypoxia when compared to the control group. Conclusions : The data shows that the effects of Woohwangcheongsim-won on neuronal death of hypoxic E18 cortical neuroblast is a significant result.

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Development of Rapid Analytical Method of Forbidden Medicines in Dietary Supplements Using LC-ESI-Tandem MS (LC-ESI-tandem MS를 이용한 기능성표방식품 중 부정유해물질 신속검사체계 개발)

  • Kim, Hee-Yun;Jang, Young-Mi;Joo, Hyun-Jin;Jung, Young-Hyun;Lee, Myoung-Sook;Park, Jong-Seok;Lee, Kwang-Ho;Lee, Hwa-Mi
    • Korean Journal of Food Science and Technology
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    • v.39 no.4
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    • pp.372-379
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    • 2007
  • A high-performance liquid chromatography-electrospray ionization (HPLC-ESI) tandem MS was developed for the rapid and simultaneous determination of forbidden medicines in dietary supplements. Thirteen medicinal components such as PDE-5 inhibitors and their analogues, and the newly identified dimethylsildenafil and xanthoanthrafil, were included in this study. After tentative standardization of molecular ions in both polarities using thirteen references on the mass spectrometer, with ESI-continuous infusion via the syringe pump method, the relative intensity of the ions present in the resulting spectra was quantitatively compared. From the results, the ion mode was selected depending on each reference's characteristics. A HPLC method coupled with the ESI mode was developed considering the matrix effect and interference depending on the type of sample. The validation test of the developed method was followed by carrying out precision, accuracy, recovery, sensitivity and linearity, etc. The method showed sufficiently high sensitivity, reproducibility, and specificity, and produced 4 times faster results when compared with the existing HPLC/UV method for the determination of forbidden compounds in dietary supplements.

Sildenafil Ameliorates Advanced Glycation End Products-Induced Mitochondrial Dysfunction in HT-22 Hippocampal Neuronal Cells

  • Sung, Soon Ki;Woo, Jae Suk;Kim, Young Ha;Son, Dong Wuk;Lee, Sang Weon;Song, Geun Sung
    • Journal of Korean Neurosurgical Society
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    • v.59 no.3
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    • pp.259-268
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    • 2016
  • Objective : Accumulation of advanced glycation end-products (AGE) and mitochondrial glycation is importantly implicated in the pathological changes of the brain associated with diabetic complications, Alzheimer disease, and aging. The present study was undertaken to determine whether sildenafil, a type 5 phosphodiesterase type (PDE-5) inhibitor, has beneficial effect on neuronal cells challenged with AGE-induced oxidative stress to preserve their mitochondrial functional integrity. Methods : HT-22 hippocampal neuronal cells were exposed to AGE and changes in the mitochondrial functional parameters were determined. Pretreatment of cells with sildenafil effectively ameliorated these AGE-induced deterioration of mitochondrial functional integrity. Results : AGE-treated cells lost their mitochondrial functional integrity which was estimated by their MTT reduction ability and intracellular ATP concentration. These cells exhibited stimulated generation of reactive oxygen species (ROS), disruption of mitochondrial membrane potential, induction of mitochondrial permeability transition, and release of the cytochrome C, activation of the caspase-3 accompanied by apoptosis. Western blot analyses and qRT-PCR demonstrated that sildenafil increased the expression level of the heme oxygenase-1 (HO-1). CoPP and bilirubin, an inducer of HO-1 and a metabolic product of HO-1, respectively, provided a similar protective effects. On the contrary, the HO-1 inhibitor ZnPP IX blocked the effect of sildenafil. Transfection with HO-1 siRNA significantly reduced the protective effect of sildenafil on the loss of MTT reduction ability and MPT induction in AGE-treated cells. Conclusion : Taken together, our results suggested that sildenafil provides beneficial effect to protect the HT-22 hippocampal neuronal cells against AGE-induced deterioration of mitochondrial integrity, and upregulation of HO-1 is involved in the underlying mechanism.

Influence of an Astronomical Observation Program on Preservice Elementary Teachers Astronomy Achievement, Astronomy Teaching Efficacy Beliefs, and Scientific Attitude (천체관측을 통한 학습이 천문성취도, 천문교수효능에 대한 신념, 과학적 태도에 미치는 효과)

  • 채동현
    • Journal of Korean Elementary Science Education
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    • v.18 no.2
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    • pp.79-101
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    • 1999
  • Astronomy is a good area to introduce a student to the study of science. The student often questions what causes the change in seasons, in the day and right, and in the rotation of stars, etc. Attempts to find answers to problems related to these astronomical observations influence the student`s intellectual development. This study is to investigate the effect of running an astronomical observations program on the preservice elementary teachers' astronomy achievement, astronomy teaching efficacy beliefs, and scientific attitude. Students consist of twenty four preservice elementary teachers. Three instruments are used: one is the astronomy achievement test, which is of an essay type, and 5 items. The other is the astronomy teaching efficacy beliefs test, which is of a Likert scale type, and 22 items. Another is the scientific attitude test, which is of the Likert scale type, and 10 items. Data are collected before and after instruction in the astronomical observations program, through the use of these tests. Data are compared. The results are: \circled1There is a significant difference between before and after instructions in the astronomy achievement test(t=11.31, p=000). \circled2There is a significant difference between before and after instructions in the astronomy teaching efficacy beliefs test(t=5.98, p=.000). \circled3There is a significant difference between before and after instructions in the scientific attitude test(t=270, pde. There fore, the a=.013). As a result, running an astronomical observations program has an effect on the preservice elementary teachers' astrono my achievement, astronomy teaching efficacy beliefs, and scientific attituuthor urges the teacher to teach astronomy through the astronomical observations in school.

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Involvement of Crosstalk Between cAMP and cGMP in Synaptic Plasticity in the Substantia Gelatinosa Neurons

  • Kim, Tae-Hyung;Chung, Ge-Hoon;Park, Seok-Beom;Chey, Won-Young;Jun, Sung-Jun;Kim, Joong-Soo;Oh, Seog-Bae
    • International Journal of Oral Biology
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    • v.36 no.2
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    • pp.83-89
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    • 2011
  • Substantia gelatinosa (SG) neurons receive synaptic inputs from primary afferent $A{\delta}$- and C-fibers, where nociceptive information is integrated and modulated by numerous neurotransmitters or neuromodulators. A number of studies were dedicated to the molecular mechanism underlying the modulation of excitability or synaptic plasticity in SG neurons and revealed that second messengers, such as cAMP and cGMP, play an important role. Recently, cAMP and cGMP were shown to downregulate each other in heart muscle cells. However, involvement of the crosstalk between cAMP and cGMP in neurons is yet to be addressed. Therefore, we investigated whether interaction between cAMP and cGMP modulates synaptic plasticity in SG neurons using slice patchclamp recording from rats. Synaptic activity was measured by excitatory post-synaptic currents (EPSCs) elicited by stimulation onto dorsal root entry zone. Application of 1 mM of 8-bromoadenosine 3,5-cyclic monophosphate (8-Br-cAMP) or 8-bromoguanosine 3,5-cyclic monophosphate (8-Br-cGMP) for 15 minutes increased EPSCs, which were maintained for 30 minutes. However, simultaneous application of 8-BrcAMP and 8-Br-cGMP failed to increase EPSCs, which suggested antagonistic cross-talk between two second messengers. Application of 3-isobutyl-1-methylxanthine (IBMX) that prevents degradation of cAMP and cGMP by blocking phosphodiesterase (PDE) increased EPSCs. Co-application of cAMP/cGMP along with IBMX induced additional increase in EPSCs. These results suggest that second messengers, cAMP and cGMP, might contribute to development of chronic pain through the mutual regulation of the signal transduction.

Genome-wide association analysis of nine reproduction and morphological traits in three goat breeds from Southern China

  • Xiaoyan, Sun;Jing, Jiang;Gaofu, Wang;Peng, Zhou;Jie, Li;Cancan, Chen;Liangjia, Liu;Nianfu, Li;Yuanyou, Xia;Hangxing, Ren
    • Animal Bioscience
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    • v.36 no.2
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    • pp.191-199
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    • 2023
  • Objective: This study aimed to investigate the significant single nucleotide polymorphisms (SNPs) and genes associated with nine reproduction and morphological traits in three breed populations of Chinese goats. Methods: The genome-wide association of nine reproduction and morphological traits (litter size, nipple number, wattle, skin color, coat color, black dorsal line, beard, beard length, and hind leg hair) were analyzed in three Chinese native goat breeds (n = 336) using an Illumina Goat SNP50 Beadchip. Results: A total of 17 genome-wide or chromosome-wide significant SNPs associated with one reproduction trait (litter size) and six morphological traits (wattle, coat color, black dorsal line, beard, beard length, and hind leg hair) were identified in three Chinese native goat breeds, and the candidate genes were annotated. The significant SNPs and corresponding putative candidate genes for each trait are as follows: two SNPs located on chromosomes 6 (CSN3) and 24 (TCF4) for litter size trait; two SNPs located on chromosome 9 (KATNA1) and 1 (UBASH3A) for wattle trait; three SNPs located on chromosome 26 (SORCS3), 24 (DYM), and 20 (PDE4D) for coat color trait; two SNPs located on chromosome 18 (TCF25) and 15 (CLMP) for black dorsal line trait; four SNPs located on chromosome 8, 2 (PAX3), 5 (PIK3C2G), and 28 (PLA2G12B and OIT3) for beard trait; one SNP located on chromosome 18 (KCNG4) for beard length trait; three SNPs located on chromosome 17 (GLRB and GRIA2), 28 (PGBD5), and 4 for hind leg hair trait. In contrast, there were no SNPs identified for nipple number and skin color. Conclusion: The significant SNPs or genes identified in this study provided novel insights into the genetic mechanism underlying important reproduction and morphological traits of three local goat breeds in Southern China as well as further potential applications for breeding goats.

Effects of Schisandra chinensis fruit extract and gomisin A on the contractility of penile corpus cavernosum smooth muscle: a potential mechanism through the nitric oxide - cyclic guanosine monophosphate pathway

  • Choi, Bo Ram;Kim, Hye Kyung;Park, Jong Kwan
    • Nutrition Research and Practice
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    • v.12 no.4
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    • pp.291-297
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    • 2018
  • BACKGROUND/OBJECTIVES: This study evaluated the effects and molecular mechanisms of the Schisandra chinensis fruit extract (SC) and its major compound gomisin A (GA), on the contractility of rabbit penile corpus cavernosum smooth muscle (PCCSM). MATERIALS/METHODS: PCCSM was exposed to SC or GA after appropriate pretreatment with nitric oxide synthase (NOS) blocker, guanylate cyclase blocker, adenylyl cyclase blocker or protein kinase A blocker. Subsequently, we evaluated the cyclic nucleotide in the perfusate by radioimmunoassay, protein expression level of neuronal NOS (nNOS) and endothelial NOS (eNOS) by western blot, and the interaction of SC or GA with udenafil and rolipram. RESULTS: Both SC and GA induce PCCSM relaxations in a concentration-dependent manner. Pretreatment with NOS blocker, guanylate cyclase blocker, adenylyl cyclase blocker or protein kinase A blocker result in significantly decreased relaxation. SC and GA also induce the levels of cyclic nucleotide in the perfusate in a concentration-dependent manner. Perfusion with GA also showed significantly higher levels of eNOS protein. Furthermore, the udenafil and rolipram induced relaxations of PCCSM were enhanced after exposure to SC and GA. Our results indicate that SC and GA induce the relaxation of PCCSM via the nitric oxide (NO)-cGMP and cAMP signaling pathways. CONCLUSIONS: The SC and GA are potential alternative treatments for men who want to consume natural products to ameliorate erectile function, or who do not respond to the commercially available medicines.