• 대한한의학방제학회지
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• 제25권4호
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• pp.457-469
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• 2017

Obesity is one of the most serious health problem because it induced numerous metabolic syndrome and increases the incidence of various disease, including diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. In 3T3-L1 adipocytes, increases in reactive oxygens species (ROS) occur with lipid accumulation. NADPH oxidase, producing superoxide anion, may contribute to the development of obesity-associated insulin resistance and type 2 diabetes. In this study, we elucidated the effect of Chaenomeles sinensis koehne extract (CSE) against the development of obesity and the inhibition mechanisms in 3T3-L1 preadiocytes. CSE decreased triglyceride content and inhibited the expression of adipogenic transcription factors including peroxisome proliferator-activated receptor $(PPAR){\gamma}$, CCAT/enhancer binding protein $(C/EBP){\alpha}$ and sterol regulatory element-binding protein (SREBP-1). In addition, CSE highly increased antioxidant activity in a dose-dependent manner. CSE remarkably reduced intracellular ROS increase and NAD(P)H oxidase activity, NOX1, NOX4, Rac1 protein expression, and phosphorylation of p47phox and p67phox We also studied the effect of CSE on weight gain induced by high-fat diet. The oral treatment of CSE (500 mg/kg, body weight) in diet-induced obese (DIO) mice showed decrease in triglyceride and adipocyte size. Therefore, these results indicate that the effect of CSE on anti-obese effects, adipocyte differentiation and reducing triglyceride contents as well as adipocyte size in obese mice, may be associated with inhibition of NAD(P)H oxidase-induced ROS production and adipose transcription factors. These results showed the potential to inhibit the obesity by CSE treatment through controlling the activation of NAD(P)H oxidase in vitro and in vivo obese model.

• 대한약리학회지
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• 제23권2호
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• pp.57-75
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• 1987

Two modalities of gonadotropin secretion, pulsatile gonadotropin and preovulatory gonadotropin surge, have been identified in the mammals. Pulsatile gonadotropin secretion is modulated by the pulsatile pattern of GnRH release and complex ovarian steroid feedback actions. The neural mechansim that regulates the pulsatile release of GnRH in the hypothalamus is called "GnRH pulse generator". Ovarian steroids, estradiol and progesterone, appear to exert thier feedback effects both directly on the pituitary to modulate gonadotropin release and on a hypothalamic site to modulate GnRH release; estradiol primarily affects the amplitude while progesterone decreases the frequency of the pulsatile GnRH. Steroid hormones are known to affect catecholamine transmission in brain. MBH-POA is richly innervated by NE systems and close apposition of NE terminals and GnRH cell bodies occurs in the MBH as well as in the POA. NE normally facilitates pulsatile LH release by acting through ${\alpha}-receptor$ mechanism. However, precise nature of facilitative role of NE transmission in maintaining pulsatile LH has not been clearly understood. Close apposition of DA and GnRH terminals in ME might permit DA to influence GnRH release. Action of DA transmission probably is mediated by axo-axonic contacts between GnRH and DA fibers in the ME. Dopamine transmission does not normally regulate pulsatile LH release, but under certain conditions, increased DA transmission inhibit LH pulse. Endogenous opioid acts to suppress the secretion of GnRH into hypophysial portal circulation, thereby inhibiting gonadotropin secretion. However, an interaction between endogenenous opioid peptides and gonadotropin release is a complex one which involves ovarian hormones as well. LH secretion appears to be most suppressed by endogenenous opioids during the luteal phase, at a time of elevated progesterone secretion. The arcuate nucleus contains not only cell bodies for GnRH and ${\beta}-endorphin$ but also a dense aborization of fibers suggesting that GnRH release is changed by the interactions between GnRH and ${\beta}-endorphin$ cell bodies within the arcuate nucleus. The frequency and amplitude of pulsatile LH release seem to be increased during the preovulatory gonadotropin surge. Estradiol exerts positive feedback action on the hypothalamo-pituitary axis to trigger preovulatory LH surge. GnRH is also crucial hormonal stimulus for preovulatory LH surge. It is unlikely, however, that increased secretion of GnRH during the preovulatory gonadotropin surge represents an obligatory neural signal for generation of the LH discharge in primates including human. Modulation of preovulatory LH surge by catecholamines has been studied almost exclusively in rats. NE and E may be involved in distinct way to accumulate GnRH in the MBH and its release into the hypophysial portal system during the critical period for LH surge on proestrus in rats. However, the mechanisms whereby augmented adrenergic transmission may facilitate the formation and accumulation of GnRH in the ME-ARC nerve terminals before the LH surge have not been clearly understood.

• Journal of Gastric Cancer
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• 제1권2호
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• pp.92-99
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• 2001

Purpose: E-cadherin is an adhesion molecule essential for tight connection between cells, forming the cadherin/catenin complex. Truncated $\beta$-catenin disrupts the interaction between E-cadherin and $\alpha$-catenin, leading to the loss of intercellular adhesion. Met protein, the hepatocyte growth factor receptor, plays important roles in signal transduction. We investigated the relationships between the expressions of E-cadherin, $\beta$-catenin, and c-met protein and the clinicopathological and prognostic parameters in gastric adenocarcinomas. Materials and Methods: The patterns of E-cadherin, $\beta$-catenin, and c-met protein expression were studied using immunohistochemistry in formalin-fixed, paraffin-embedded archival tissues from 76 surgically resected gastric adenocarcinomas. Results: Increased expressions of E-cadherin, $\beta$-catenin, and c-met were more significantly correlated in early gastric cancers (EGC) than in advanced gastric cancers (AGC) (P=0.002, P=0.003 and P=0.026). The positive immunoreactivities of all three markers were markedly lower in signet ring-cell type and poorly differentiated type lesions than in intestinal-type lesions. Decreased expression of the $\beta$-catenin protein correlated well with increased tumor invasion depth (P=0.039), and increased lymph node metastasis correlated well with reduced expression of c-met (P=0.046). Conclusion: In gastric cancers, reduced expressions of the E-cadherin, $\beta$-catenin, and c-met proteins may play some role in poorer tumor differentiation, deeper tumor invasion, and increased lymph node metastasis. Also, the c-met gene is thought to play a specific role in the mechanism of the yet unknown catenin action.

• Molecules and Cells
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• 제37권1호
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• pp.66-73
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• 2014

Myeloid-derived suppressor cells (MDSCs) play an important role in impairing the function of T cells. We characterized MDSCs in two chronic hepatitis C (CHC) cohorts: a cross-sectional group that included 61 treatment-naive patients with CHC, 14 rapid virologic response (RVR) cases and 22 early virologic response (EVR) cases; and a longitudinal group of 13 cases of RVR and 10 cases of EVR after pegylated-interferon-${\alpha}$/ribavirin treatment for genotype 1b HCV infection. Liver samples from 32 CHC patients and six healthy controls were subjected to immunohistochemical analysis. MDSCs frequency in treatment-naive CHC was significantly higher than in RVR, EVR, or healthy subjects and was positively correlated with HCV RNA. Patients infected with HCV genotype 2a had a significantly higher frequency of MDSCs than those infected with genotype 1b. Decreased T cell receptor (TCR) ${\zeta}$ expression on $CD8^+$ T cells was significantly associated with an increased frequency of MDSCs in treatment-naive CHC patients and was restored by L-arginine treatment in vitro. Increased numbers of liver arginase-$1^+$ cells were closely associated with the histological activity index in CHC. The TCR ${\zeta}$ chain was significantly downregulated on hepatic $CD8^+$ T cells in CHC. During antiviral follow up, MDSCs frequency in peripheral blood mononuclear cells was directly correlated with the HCV RNA load in the plasma and inversely correlated with TCR ${\zeta}$ chain expression in $CD8^+$ T cells in both RVR and EVR cases. Notably, the RVR group had a higher frequency of MDSCs at baseline than the EVR group. Collectively, this study provides evidence that MDSCs might be associated with HCV persistence and downregulation of CD8 ${\zeta}$ chain expression.

• Journal of Ginseng Research
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• 제46권6호
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• pp.759-770
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• 2022

Background: Aerobic cellular respiration provides chemical energy, adenosine triphosphate (ATP), to maintain multiple cellular functions. Sirtuin 1 (SIRT1) can deacetylate peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) to promote mitochondrial biosynthesis. Targeting energy metabolism is a potential strategy for the prevention and treatment of various diseases, such as cardiac and neurological disorders. Ginsenosides, one of the major bioactive constituents of Panax ginseng, have been extensively used due to their diverse beneficial effects on healthy subjects and patients with different diseases. However, the underlying molecular mechanisms of total ginsenosides (GS) on energy metabolism remain unclear. Methods: In this study, oxygen consumption rate, ATP production, mitochondrial biosynthesis, glucose metabolism, and SIRT1-PGC-1α pathways in untreated and GS-treated different cells, fly, and mouse models were investigated. Results: GS pretreatment enhanced mitochondrial respiration capacity and ATP production in aerobic respiration-dominated cardiomyocytes and neurons, and promoted tricarboxylic acid metabolism in cardiomyocytes. Moreover, GS clearly enhanced NAD⁺-dependent SIRT1 activation to increase mitochondrial biosynthesis in cardiomyocytes and neurons, which was completely abrogated by nicotinamide. Importantly, ginsenoside monomers, such as Rg1, Re, Rf, Rb1, Rc, Rh1, Rb2, and Rb3, were found to activate SIRT1 and promote energy metabolism. Conclusion: This study may provide new insights into the extensive application of ginseng for cardiac and neurological protection in healthy subjects and patients.

• Animal Bioscience
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• 제36권3호
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• pp.521-528
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• 2023

Objective: This study investigated the effects of surgical castration on behavior, physiological and inflammatory indicators, and leukocyte cytokine mRNA levels in Korean cattle bull calves. Methods: Nineteen Korean cattle bull calves (average body weight, 254.5 kg; average age, 8.2 months) were divided into two treatment groups: control (n = 9) and castration (n = 10). Surgical castration was performed using Newberry knives and a Henderson castrating tool. Blood was obtained just before castration (0 h) and at 0.5 h, 6 h, 1 d, 3 d, 7 d, and 14 d after castration. Plasma cortisol (PC), saliva cortisol (SC), plasma substance P, and plasma haptoglobin concentrations, and the leucocyte mRNA levels of the interleukin-1-alpha (IL1A), interleukin-1-beta (IL1B), interleukin-1 receptor antagonist (IL1RN), and interleukin-6 (IL6) genes were analyzed. Results: Castration decreased (p<0.01) the average daily gain and gain/feed ratio. Castration reduced the time spent eating (p<0.001) and the eating frequency (p<0.01) and increased (p<0.001) the lying frequency. Castration temporarily increased (p<0.05) circulating PC and SC concentrations at 0.5 h after castration. Castration temporarily increased (p<0.05) plasma substance P concentrations at 1 d after castration. Castration increased (p<0.05) plasma haptoglobin concentrations at 1 and 3 d after castration. Castration increased (p<0.05) leukocyte mRNA levels of the IL1A, IL1B, IL1RN, and IL6 genes at 6 h after castration. Conclusion: Castration temporarily induced stress and expression of leucocyte inflammatory cytokine genes in Korean cattle bull calves.

• Tuberculosis and Respiratory Diseases
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• 제43권3호
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• pp.308-322
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• 1996

연구배경 : 히스타민은 폐혈관주위의 비만 세포내에 풍부하게 분포하니 아직까지 급성 폐손상의 병리기전에 있어 히스타민의 역할에 대해서는 규명되어 있지 않았다. 히스타민은 IL-1 이나 IL-8과 같은 cytokine 사이에 상호작용이 있고 혈관내피 표면상에 P-selectin의 표현을 증가시키는 것으로 알려져 있다. 이에 저자들은 건강한 백서의 기도내로 침윤이 증가되며 히스타민과 TNF를 병용 투여서는 TNF 단독 투여사보다 폐장내 호중구의 침윤이 증폭되고 폐손상의 정도가 증가 될 것으로 가정하였다. 방법 : 몸무게 270-370gm인 Sprague-Dawley 쥐를 사용하여 정상군은 생리식염수 0.5mL을, 치료군은 체증 1Kg 당 $1.1{\mu}g$, $11{\mu}g$ 및 $55{\mu}g$의 히스타민을 단독 혹은 TNF 500ng과 함께 병용하여 기도로 투여하거나 히스타민 $55{\mu}g$과 IL-1 50ng을 병용투여 한 뒤 5시간 뒤 에 폐조직 내 myeloperoxidase(MPO) 활성도와 폐포액내 호중구 수 및 쥐의 IL-8으로 고려되는 cytokine-induced neutrophil chemoattractant(CINC)의 활성도 그리고 폐혈관내 알부민의 폐조직내로의 누출을 측정하였다. 또한 TNF와 히스타민을 병용투여한 뒤 TNF와 히스타민 병용치료군에 항히스타민제를 경정맥내로 주입한 뒤 동일한 방법으로 각 지표들을 측정하여, 관찰된 상승효과가 차단되는지를 보았다. 곁과 1) TNF치료군은 정상군에 비하여 폐장내 MPO 활성도, 기관폐포액내 홍중구수 및 폐혈관의 누출이 더 높게 나타났으며(각 p<0.001), 히스타면 투여군은 11 및 $55{\mu}g/kg$ 투여군에서 정상군에 비해 MPO 활성도만이 높게 나타났다(p<0.05) 2) 폐장내 MPO 활성도는 기도내로 TNF와 병용투여한 히스타민 $1.1{\mu}g$군, $11{\mu}g$군 및 $55{\mu}g$ 군 모두에서 정상군에 비해 증가되어 나타났으며(각 p<0.001) 히스타민 $11{\mu}g/kg$ 병합투여군에서는 TNF 단독치료군에 비해서도 높게 나타났다(p=0.0251). 기관폐포액내 호중구의 수는 히스타민 1.1, 11 및 $55{\mu}g/kg$군 모두에서 정상군(p<0.05)에 비해 증가되어 나타났으며 $1.1{\mu}g/kg$군은 TNF 단독치료군에 비해서도 높았다(p=0.0367). 급성 폐혈관 히스타민 $1.1{\mu}g$군, $11{\mu}g$군 $55{\mu}g$군에서 정상군에 비해 증가되었으나(p<0.001), TNF 치료군과는 차이가 없었다. 3) TNF와 히 스타민 1.1, 11 및 $55{\mu}g/kg$이 병용투여된 군 모두에서 정상군에 비해 폐포 세척액내 CINC 활성도가 유의하게 증가되었다(각각 p-값<0.01 및< 0.05) 4) $H_1$ 수용체차단제인 mepyramine과 $H_2$ 수용체차단제인 ranitidine 세척액내 증폭되었던 호중구 수 및 CINC의 활성도를 감소시켰다(각각 p-값>0.05) 5) IL-1과 병용 투여한 히스타민은 정상군에 비해 MPO 활성도 및 급성 폐혈관 누출이 증가되었으나(p<0.05), IL-1 치료군과는 차이가 없었다. 결론 : 본연구의 결과로서 백서의 기도내로 국소적으로 히스타민을 투여시 5시간 이내에 폐조직내 호중구의 침윤이 증가되고 TNF로 유도된 폐조직내 MPO 활성도 및 기관폐포액 내 호중구 수의 증가가 증폭되나 폐혈관내 알부민의 폐장내 누출의 증폭작용이 없고 IL-1으로 유도된 폐손상에도 급성 폐손상의 증폭작용이 관찰되지 않으므로 TNF나 IL-1으로 유도되는 급성 폐손상에 히스타민 병용 투여에 의한 폐손상의 증폭작용은 없을 것으로 사료되었다.

• 대한약리학회지
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• 제30권3호
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• pp.273-289
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• 1994

뇌-허혈후 나타나는 신경세포의 손상에 glutamate의 과다한 유리와 그의 N-methyl-D-aspartate (NMDA) 수용체: calcium 통로 활성작용 및 polyamine중 putrescine의 증가로 인한 신경세포내 $[Ca^{2+}]$의 상승과 관련 있다는 보고들이 있다. 본 연구에서는 Mongolian gerbil에서 5분간 경동맥을 차단하여 뇌-허혈을 가한후 재관류시 해마의 세포외액내 polyamine, glutamate, acetylcholine농도, 해마의 $[^3H]MK-801$ 결합능의 변동 및 해마조직소견의 변동에 미치는 비가역성 ornithine decarboxylase (ODC) 억제제인 difluoromethylornithine (DFMO), diamine oxidase (DAO) 억제제인 aminoguanidine (AG), NMDA 수용체 길항제인 MK-801 및 calcium 통로 차단제인 nimodipine (NM)의 효과를 비교-검색하였다. 해마 세포외액내 polyamine, glutamate 및 acetylcholine은 microdialysis probe를 해마의 CA1부위에 위치시킨 후 나온 분취액을 HPLC와 luminometer를 사용하여 측정하였고, 해마조직에서 신경세포의 손상은 cresyl-violet 염색법으로 관찰하였다. 허혈후 해마 세포외액내 putrescine농도는 5분이내에 급속히 증가하여 뇌-허혈후 96시간까지 증가되는 경향을 보였으며 AG과 MK-801 처치시 saline 처치군에 비하여 증가정도가 상승되었으나 NM과 DFMO 처치로 putrescine의 증가는 감소되는 경향을 보였다. 해마 세포외액내 glutamate의 농도는 허혈후 5분 이내에 9배이상 유의하게 증가한 후 급격히 감소되어 25분후에는 정상치로 회복되었으나, 이같은 변동은 AG, DFMO 및 MK-801 처치로 영향을 받지 않았고 NM 처치로는 glutamate의 증가가 둔화되는 경향을 보였다. 해마 세포외액내 acetylcholine 농도는 허혈에 의하여 큰변동이 없었으나 허혈전 acetylcholine농도는 DFMO나 MK-801처치로 감소되는 경향을 보였다. 해마-synaptosome막의 $[^3H]MK-801$ 결합능은 saline 처치군에 비하여 AG과 MK-801 처치로 유의하게 감소되었다. 해마의 조직소견상 AG과 NM은 허혈후의 신경세포손상을 억제하고, MK-801은 손상의 예방에 별 영향을 주지 못하였으나 DFMO는 허혈에 의한 신경세포의 손상을 더욱 악화시키는 경향을 보였다. 이상의 결과로 미루어 NM과 다른기전으로 AG은 해마신경세포의 손상을 NMDA-수용체: calcium 통로의 활성화를 조절하여 허혈성 뇌손상을 억제할 수 있으리라 사료된다.

• 대한약리학회지
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• 제28권1호
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• pp.61-74
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• 1992

마취가토에서 혈압유지에 중요한 역할을 하고 있는 교감신경계, renin-angiotensin계, vasopressin계를 차단하였을때의 혈압자체의 변동과 norepinephrine (NE), angiotensin II (AII) 및 vasopressin (VP)의 승압효과의 변동을 조사하였다. 교감신경계와 renin-angiotensin계의 차단에는 각각 교감신경절 차단약인 chlorisondamine (CS)과 pirenzepine (PZ), angiotensin 변환효소억제약인 enalapril (ENAL)를 사용하였다. VP계의 차단에는 혈장 VP농도를 하강시킴이 알려져 있는 kappa opioid 수용체의 작용약인 bremazocine (BREM)을 사용하였다. CS (0.4mg/kg), ENAL (2mg/kg), BREM (0.25mg/kg)은 각각 비슷한 정도의 저혈압상태를 일으켰다. BREM에 의한 저혈압은 VP와 같은 효과를 가진 합성약인 desmopressin으로 유의하게 길항되었으며 BREM에 의한 저혈압이 적어도 일부 혈장 VP농도의 하강과 관계있음을 시사하였다. CS는 ENAL 또는 BREM으로 하강된 혈압을, ENAL은 CS 또는 BREM으로 하강된 혈압을, BREM은 CS 또는 ENAL로 하강된 혈압을, 더욱 하강시켰다. CS, PZ 그리고 ENAL 또는 CS, PZ 그리고 BREM에 의한 저혈압은 CS이외의 세약물에 의한 저혈압보다 심하였다. CS는 NE에 의한 승압효과 뿐만아니라 AII와 VP의 승압효과도 강화시켰다. AII의 승압효과는 또 ENAL과 BREM으로도 증대되었다. VP의 승압효과는 BREM으로도 강화되었다. ${\alpha}$-수용체의 길항약인 phentolamine과 phenoxybenzamine은 AII와 VP승압효과를 강화시켰다. 3승압계 차단이 혈압자체에 미치는 실험결과는 3계가 모두 혈압조절에 관여하고 그 중에서도 교감신경계가 가장 큰 역할을 하고 있음을 가리키고 있다. 한 승압계의 차단하에서, 그 계의 승압 hormone 뿐만아니라 다른 계의 승압 hormone의 승압효과도 증대됨은 이 3승압계가 긴밀한 상호작용을 하고 있는 증거이다.

• Asian-Australasian Journal of Animal Sciences
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• 제30권11호
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• pp.1620-1632
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• 2017

Objective: This study evaluated the effects of a traditional Chinese medicine formula (TCMF) on muscle fiber characteristics in finishing pigs and the effects of the formula's extract (distilled water, ethyl acetate and petroleum ether extraction) on porcine cell proliferation and isoforms of myosin heavy chain (MyHC) gene expression in myocytes. Methods: In a completely randomized design, ninety pigs were assigned to three diets with five replications per treatment and six pigs per pen. The diets included the basal diet (control group), TCMF1 (basal diet+2.5 g/kg TCMF) and TCMF2 (basal diet+5 g/kg TCMF). The psoas major muscle was obtained from pigs at the end of the experiment. Muscle fiber characteristics in the psoas major muscle were analyzed using myosin ATPase staining. Cell proliferation was measured using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) dye and cytometry. Isoforms of MyHC gene expression were detected by real-time quantitative polymerase chain reaction. Results: The final body weight and carcass weight of finishing pigs were increased by TCMF1 (p<0.05), while the psoas major muscle cross-sectional area was increased by TCMF (p<0.05). The cross-sectional area and diameter of psoas major muscle fiber Ι, IIA, and IIB were increased by TCMF2 (p<0.05). The cross-sectional area and fiber diameter of psoas major muscle fiber IIA and IIB were increased by diet supplementation with TCMF1 (p<0.05). Psoas major muscle fiber IIA and IIB fiber density from the pigs fed the TCMF1 diet and the type IIB fiber density from the pigs fed the TCMF2 diet were lower compared to pigs fed the control diet (p<0.05). Pigs fed TCMF2 had a higher composition of type Ι fiber and a lower percentage of type IIB fiber in the psoas major muscle (p<0.05). The expression levels of MyHC Ι, MyHC IIa, and MyHC IIx mRNA increased and the amount of MyHC IIb mRNA decreased in the psoas major muscle from TCMF2, whereas MyHC Ι and MyHC IIx mRNA increased in the psoas major muscle from TCMF1 (p<0.05). Peroxisome proliferator-activated receptor ${\gamma}$ $coactivator-1{\alpha}$ and CaN mRNA expression in the psoas major muscle were up-regulated by TCMF (p<0.05). Porcine skeletal muscle satellite cell proliferation was promoted by $4{\mu}g/mL$ and $20{\mu}g/mL$ TCMF water extraction (p<0.05). Both $1{\mu}g/mL$ and $5{\mu}g/mL$ of TCMF water extraction increased MyHC IIa, MyHC IIb, and MyHC IIx mRNA expression in porcine myocytes (p<0.05), while MyHC Ι mRNA expression in porcine myocytes was decreased by $5{\mu}g/mL$ TCMF water extraction (p<0.05). Porcine myocyte MyHC Ι and MyHC IIx mRNA expression were increased, and MyHC IIa and MyHC IIb mRNA expression were down-regulated by $5{\mu}g/mL$ TCMF ethyl acetate extraction (p<0.05). MyHC Ι and MyHC IIa mRNA expression in porcine myocytes were increased, and the MyHC IIb mRNA expression was decreased by $1{\mu}g/mL$ TCMF ethyl acetate extraction (p<0.05). Four isoforms of MyHC mRNA expression in porcine myocytes were reduced by $5{\mu}g/mL$ TCMF petroleum ether extraction (p<0.05). MyHC IIa mRNA expression in porcine myocytes increased and MyHC IIb mRNA expression decreased by $1{\mu}g/mL$ in a TCMF petroleum ether extraction (p<0.05). Conclusion: These results indicated that TCMF amplified the psoas major muscle cross-sectional area through changing muscle fiber characteristics in finishing pigs. This effect was confirmed as TCMF extraction promoted porcine cell proliferation and affected isoforms of MyHC gene expression in myocytes.