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Ginsenoside compound K protects against cerebral ischemia/ reperfusion injury via Mul1/Mfn2-mediated mitochondrial dynamics and bioenergy

  • Qingxia Huang;Jing Li;Jinjin Chen;Zepeng Zhang;Peng Xu;Hongyu Qi;Zhaoqiang Chen;Jiaqi Liu;Jing Lu;Mengqi Shi;Yibin Zhang;Ying Ma;Daqing Zhao;Xiangyan Li
    • Journal of Ginseng Research
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    • v.47 no.3
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    • pp.408-419
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    • 2023
  • Background: Ginsenoside compound K (CK), the main active metabolite in Panax ginseng, has shown good safety and bioavailability in clinical trials and exerts neuroprotective effects in cerebral ischemic stroke. However, its potential role in the prevention of cerebral ischemia/reperfusion (I/R) injury remains unclear. Our study aimed to investigate the molecular mechanism of ginsenoside CK against cerebral I/R injury. Methods: We used a combination of in vitro and in vivo models, including oxygen and glucose deprivation/reperfusion induced PC12 cell model and middle cerebral artery occlusion/reperfusion induced rat model, to mimic I/R injury. Intracellular oxygen consumption and extracellular acidification rate were analyzed by Seahorse multifunctional energy metabolism system; ATP production was detected by luciferase method. The number and size of mitochondria were analyzed by transmission electron microscopy and MitoTracker probe combined with confocal laser microscopy. The potential mechanisms of ginsenoside CK on mitochondrial dynamics and bioenergy were evaluated by RNA interference, pharmacological antagonism combined with co-immunoprecipitation analysis and phenotypic analysis. Results: Ginsenoside CK pretreatment could attenuate mitochondrial translocation of DRP1, mitophagy, mitochondrial apoptosis, and neuronal bioenergy imbalance against cerebral I/R injury in both in vitro and in vivo models. Our data also confirmed that ginsenoside CK administration could reduce the binding affinity of Mul1 and Mfn2 to inhibit the ubiquitination and degradation of Mfn2, thereby elevating the protein level of Mfn2 in cerebral I/R injury. Conclusion: These data provide evidence that ginsenoside CK may be a promising therapeutic agent against cerebral I/R injury via Mul1/Mfn2 mediated mitochondrial dynamics and bioenergy.

Synthesis of Cyclen-Based Copper Complexes as a Potential Estrogen Receptor Ligand (에스트로젠 수용체 리간드로서 사이클렌을 기본 구조로 한 구리 착물의 합성)

  • Park, Jeong-Chan;Pandya, Darpan N.;Jeon, Hak-Rim;Lee, Sang-Woo;Ahn, Byeong-Cheol;Lee, Jae-Tae;Yoo, Jeong-Soo
    • Nuclear Medicine and Molecular Imaging
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    • v.41 no.4
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    • pp.326-334
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    • 2007
  • Purpose: The estrogen receptor (ER), which is over-expressed in ER-positive breast tumors, has been imaged by positron emission tomography (PET) using $[^{18}F]$ labeled estrogen ligands, especially $[^{18}F]FES$. However, $[^{18}F]$ has relatively short-lived half-life ($t_{1/2}$ =1.8 h) and the labeling yield of radio-fluorination is usually low compared with $^{64}Cu\;(t_{1/2}=12.7\;h)$. 1,4,7,10-tetraazacyclododecane (cyclen) is used to form stable metal complexes with copper, indium, gallium, and gadolinium. With these in mind, we prepared cyclen-based Cu complexes which mimic estradiol in aspect of two hydroxyl groups. Materials and Methods: 1.7-Protected cyclen, 1.7-bis (benzyloxycarbonyl)-cyclen was synthesized according to the reported procedure. After introducing two 4-benzyloxybenzyl groups at 4,10-positions, the benzyloxycarbonyl and benzyl groups were removed at the same time by hydrogenation on Pd/C to give 1,7-bis(4-hydroxybenzyl)-1,4,7,10-tetraazacyclododecane (1). Results: The prepared ligand 1 was fully characterized by $^1H,\;^{13}C$ NMR, and mass spectrometer. The synthesized ligand was reacted with copper chloride and copper perchlorate to give copper complexes $[Cu(1)]^{2+}2(CIO_4^-)\;and\;[Cu(1)Cl]^+Cl^-$ which were confirmed by high-resolution mass (FAB). Conclusion: We successfully synthesized a cyclen derivative of which two phenol groups are located on trans position of N-atoms. And, two Cu(ll) complexes of +2 and +1 overall charge, were prepared as a potential PET tracers for ER imaging.

Blockade of Thromboxane Influences Does Not Affect Renal Blood Flow Deficit in Anesthetized Diabetic Rats (마취된 당뇨 흰쥐의 신혈류량 감소에 관여하는 기전 : 내인성 쓰롬복산계의 무관성)

  • Ha, Hun-Joo;Dunham, Earl W.
    • The Korean Journal of Pharmacology
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    • v.24 no.2
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    • pp.221-232
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    • 1988
  • Studies were conducted to determine whether reduced renal blood flow (RBF) exhibited by rats with uncontrolled, streptozotocin (STZ)-induced diabetes is attributable to diabetes-associated, enhanced renal vasoconstrictor influence of endogenous thromboxane $(TX)A_2$. Rats which were injected with STZ after pretreatment with 3-O-methyl glucose (3OMG), an agent which prevents STZ-induced hyperglycemia, were also studied. Basal values of total RBF (RBF; ml $min^{-1}$ $gKw^{-1}$; electromagnetic flow probe), systemic arterial pressure (BP; mm Hg) and renal vascular resistance (RVR;BP $RBF^{-1})$in pentobarbital-anesthetized rats during a control period were $5.9{\pm}0.3$(P<0.1_{VS}. CR), $115{\pm}3$ and $20.3{\pm}1.0$(P<0.1_{VS}. CR) for STZR (n=15), and $8.4{\pm}0.4$, $123{\pm}3$ and $15.1{\pm}0.8$ for age-matched control rats (CR; n= 15), respectively. Basal values of RBF, BP and RVR in 3OMG pretreated STZR were identical to CR. In preparations shown capable of renal vasodilatation, OKY 1581 (1 mg/kg, i.v. followed by 0.4 mg/kg min infusion) abolished arachidonate-induced $(TX)A_2$ synthesis, but did not alter basal BP, RBF or RVR in either STZR or CR (n=4/group). Similarly, i.r.a. infusion of SQ29548 (100 ng/ml RBF) abolished renal vasoconstriction induced by a TX/prostaglandin endoperoxide mimic, U46619, but had no discern able affect on RVR in either STZR (n=8) or CR (n=8). The data indicates that $TXA_2$ does not participate in the elevated basal RVR of STZR which are associated with the diabetic state.

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The Reserch on Actual Condition of Crime of Arson Which Occurs in Korea and Its Countermeasures (방화범죄의 실태와 그 대책 - 관심도와 동기의 다양화에 대한 대응 -)

  • Choi, Jong-Tae
    • Korean Security Journal
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    • no.1
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    • pp.371-408
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    • 1997
  • This article is the reserch on actual condition of crime of arson which occurs in Korea and its countermeasures. The the presented problem in this article are that (1) we have generally very low rate concern about the crime of arson contrary to realistic problems of rapid increase of crime of arson (2) as such criminal motives became so diverse as to the economic or criminal purpose unlike characteristic and mental deficiency of old days, and to countermeasure these problems effectively it presentation the necessity of systemantic research. Based on analysis of reality of arson, the tendency of this arson in Korea in the ratio of increase is said to be higher than those in violence crime or general fire rate. and further its rate is far more greater than those of the U.S.A. and Japan. Arson is considered to be a method of using fire as crime and in case of presently residence to be the abject, it is a public offense crime which aqccompany fatality in human life. This is the well It now fact to all of us. And further in order to presentation to the crime of arson, strictness of criminal law (criminal law No, 164 and 169, and fire protection law No. 110 and 111) and classification of arsonist as felony are institutionary reinforced to punish with certainty of possibility, Therefore, as tendency of arson has been increased compared to other nations, it is necessary to supplement strategical policy to bring out overall concerns of the seriousness of risk and damage of arson, which have been resulted from the lack of understanding. In characteristics analysis of crime of arson, (1) It is now reveald that, in the past such crime rate appeared far more within the boundary of town or city areas in the past, presently increased rate of arsons in rural areas are far more than in the town or small city areas, thereby showing characteristics of crime of arson extending nation wide. (2) general timetable of arson shows that night more than day time rate, and reveald that is trait behavior in secrecy.(3) arsonists are usually arrested at site or by victim or report of third person(82,9%).Investigation activities or self surrenders rate only 11.2%. The time span of arrest is normally the same day of arson and at times it takes more than one year to arrest. This reveals its necessity to prepare for long period of time for arrest, (4) age rate of arson is in their thirties mostly as compared to homicide, robbery and adultery, and considerable numbers of arsons are in old age of over fifties. It reveals age rate is increased (5) Over half of the arsonists are below the junior high school (6) the rate of convicts by thier records is based on first offenders primarily and secondly more than 4 time convicts. This apparently shows necessity of effective correctional education policy for their social assimilation together with re-investigation of human education at the primary and secondary education system in thier life. The examples of motivation for arosnits, such as personal animosity, fury, monetary swindle, luscious purpose and other aims of destroying of proof, and other social resistance, violence including ways of threatening, beside the motives of individual defects, are diverse and arsonic suicide and specifically suicidal accompany together keenly manifested. When we take this fact with the criminal theory, it really reveals arsons of crime are increasing and its casualities are serious and a point as a way of suicide is the anomie theory of Durkheim and comensurate with the theory of that of Merton, Specifically in the arson of industrial complex, it is revealed that one with revolutionary motive or revolting motive would do the arsonic act. For the policy of prevention of arsons, professional research work in organizational cooperation for preventive activities is conducted in municipal or city wise functions in the name of Parson Taskforces and beside a variety of research institutes in federal government have been operating effectively to countermeasure in many fields of research. Franch and Sweden beside the U.S. set up a overall operation of fire prevention research funtions and have obtained very successful result. Japan also put their research likewise for countermeasure. In this research as a way of preventive fire policy, first, it is necessary to accomodate the legal preventitive activities for fire prevention in judicial side and as an administrative side, (1) precise statistic management of crime of arson (2) establishment of professional research functions or a corporate (3) improvement of system for cooperative structural team for investigation of fires and menpower organization of professional members. Secondly, social mentality in individual prospect, recognition of fires by arson and youth education of such effect, educational program for development and practical promotion. Thirdly, in view of environmental side, the ways of actual performance by programming with the establishment of cooperative advancement in local social function elements with administrative office, habitants, school facilities and newspapers measures (2) establishment of personal protection where weak menpowers are displayed in special fire prevention measures. These measures are presented for prevention of crime of arson. The control of crime and prevention shall be prepared as a means of self defence by the principle of self responsibility Specifically arsonists usually aims at the comparatively weak control of fire prevention is prevalent and it is therefore necessary to prepare individual facilities with their spontaneous management of fire prevention instead of public municipal funtures of local geverment. As Clifford L. Karchmer asserted instead of concerns about who would commit arson, what portion of area would be the target of the arson. It is effective to minister spontaveously the fire prevention measure in his facility with the consideration of characteristics of arson. On the other hand, it is necessary for the concerned personnel of local goverment and groups to distribute to the local society in timely manner for new information about the fire prevention, thus contribute to effective result of fire prevention result. In consideration of these factors, it is inevitable to never let coincide with the phemonemon of arsons in similar or mimic features as recognized that these could prevail just an epedemic as a strong imitational attitude. In processing of policy to encounter these problems, it is necessary to place priority of city policy to enhancement of overall concerns toward the definitive essense of crime of arson.

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A Novel in Vitro Method for the Metabolism Studies of Radiotracers Using Mouse Liver S9 Fraction (생쥐 간 S9 분획을 이용한 방사성추적자 대사물질의 새로운 체외 측정방법)

  • Ryu, Eun-Kyoung;Choe, Yearn-Seong;Kim, Dong-Hyun;Lee, Sang-Yoon;Choi, Yong;Lee, Kyung-Han;Kim, Byung-Tae
    • The Korean Journal of Nuclear Medicine
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    • v.38 no.4
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    • pp.325-329
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    • 2004
  • Purpose: Usefulness of mouse liver S9 fraction was evaluated for the measurement of the metabolites in the in vitro metabolism study of $^{18}F$-labeled radiotracers. Materials and Methods: Mouse liver S9 fraction was isolated at au early step in the course of microsome preparation. The in vitro metabolism studies were tarried out by incubating a mixture containing the radiotracer, S9 fraction and NADPH at $37^{\ciirc}C$, and an aliquot of the mixture was analyzed at the indicated time points by radio-TLC. Metabolic defluorination was further confirmed by the incubation with calcium phosphate, a bone mimic. Results: The radiotracer $[^{18}F]1$ underwent metabolic defluorination within 15 min, which was consistent with the results of the in vivo method and the in vitro method using microsome. Radiotracer $[^{18}F]2$ was metabolized to three metabolites including $4-[^{18}F]fluorobenzoic$ acid within 60 min. It is likely that the one of these metabolites at the origin of radio-TLC was identical with the one that obtained from the in vivo and in vitro (microsome) method. Compared with the in vitro method using microsome, the method using S9 fraction gave a similar pattern of the metabolites but with a different ratio, which can be explained by the presence of cytosol in the S9 fraction. Conclusion: These results suggest that the findings of the in vitro metabolism studies using S9 fraction can reflect the in vivo metabolism of novel radiotracers in the liver. Moreover, this method can be used as a tool to determine metabolic defluorination along with calcium phosphate absorption method.

The Clinical Features of Endobronchial Tuberculosis - A Retrospective Study on 201 Patients for 6 years (기관지결핵의 임상상-201예에 대한 후향적 고찰)

  • Lee, Jae Young;Kim, Chung Mi;Moon, Doo Seop;Lee, Chang Wha;Lee, Kyung Sang;Yang, Suck Chul;Yoon, Ho Joo;Shin, Dong Ho;Park, Sung Soo;Lee, Jung Hee
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.5
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    • pp.671-682
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    • 1996
  • Background : Endobronchial tuberculosis is definded as tuberculous infection of the tracheobronchial tree with microbiological and histopathological evidence. Endobronchial tuberculosis has clinical significance due to its sequela of cicatrical stenosis which causes atelectasis, dyspnea and secondary pneumonia and may mimic bronchial asthma and pulmanary malignancy. Method : The authors carried out, retrospectively, a clinical study on 201 patients confirmed with endobronchial tuberculosis who visited the Department of Pulmonary Medicine at Hangyang University Hospital from January 1990 10 April 1996. The following results were obtained. Results: 1) Total 201 parients(l9.5%) were confirmed as endobronchial tuberculosis among 1031 patients who had been undergone flexible bronchofiberscopic examination. The number of male patients were 55 and that of female patients were 146. and the male to female ratio was 1 : 2.7. 2) The age distribution were as follows: there were 61(30.3%) cases in the third decade, 40 cases(19.9%) in the fourth decade, 27 cases(13.4%) in the sixth decade, 21 cases(10.4%) in the fifth decade, 19 cases(9.5%) in the age group between 15 and 19 years, 19 cases(9.5%) in the seventh decade, and 14 cases(7.0%) over 70 years, in decreasing order. 3) The most common symptom, in 192 cases, was cough 74.5%, followed by sputum 55.2%, dyspnea 28.6%, chest discomfort 19.8%, fever 17.2%, hemoptysis 11.5%, in decreasing order, and localized wheezing was heard in 15.6%. 4) In chest X-ray of 189 cases, consolidation was the most frequent finding in 67.7%, followed by collapse 43.9%. cavitary lesion 11.6%, pleural effusion 7.4%, in decreasing order, and there was no abnormal findings in 3.2%. 5) In the 76 pulmanary function tests, a normal pattern was found in 44.7%, restrictive pattern in 39.5 %, obstructive pattern in 11.8%, and combined pattern in 3.9%. 6) Among total 201 patients, bronchoscopy showed caseous pseudomembrane in 70 cases(34.8%), mucosal erythema and edema in 54 cases(26.9%), hyperplastic lesion in 52 cases(25.9%), fibrous s.enosis in 22 cases(10.9%), and erosion or ulcer in 3 cases(1.5%). 7) In total 201 cases, bronchial washing AFB stain was positive in 103 cases(51.2%), bronchial washing culture for tuberculous bacilli in 55 cases(27.4%). In the 99 bronchoscopic biopsies, AFB slain positive in 36.4%. granuloma without AFB stain positive in 13.1%, chronic inflammation only in 36.4%. and non diagnostic biopsy finding in 14.1%. Conclusions : Young female patients, whose cough resistant to genenal antitussive agents, should be evaluated for endobronchial tuberculosis, even with clear chest roentgenogram and negative sputum AFB stain. Furthermore, we would like to emphasize that the bronchoscopic approach is a substantially useful means of making a differential diagnosis of atelectasis in older patients of cancer age. At this time we have to make a standard endoscopic classification of endobronchial tuberculosis, and well designed prospective studies are required to elucidate the effect of combination therapy using antituberculous chemotherapy with steroids on bronchial stenosis in patients with endobronchial tuberculosis.

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