• Title/Summary/Keyword: E/I imbalance

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Biological Functions of N- and O-linked Oligosaccharides of Equine Chorionic Gonadotropin and Lutropin/Chorionicgonadotropin Receptor

  • Min, K. S.
    • Proceedings of the KSAR Conference
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    • 2000.10a
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    • pp.10-12
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    • 2000
  • Members of the glycoprotein family, which includes CG, LH, FSH and TSH, comprise two noncovalently linked $\alpha$- and $\beta$-subunits. Equine chorionic gonadotropin (eCG), known as PMSG, has a number of interesting and unique characteristics since it appears to be a single molecule that possesses both LH- and FSH-like activities in other species than the horse. This dual activity of eCG in heterologous species is of fundamental interest to the study of the structure-function relationships of gonadotropins and their receptors. CG and LH $\beta$ genes are different in primates. In horse, however, a single gene encodes both eCG and eLH $\beta$-subunits. The subunit mRNA levels seem to be independently regulated and their imbalance may account for differences in the quantities of $\alpha$ - and $\beta$ -subunits in the placenta and pituitary. The dual activities of eCG could be separated by removal of the N-linked oligosaccharide on the $\alpha$-subunit Asn 56 or CTP-associated O-linked oligosaccharides. The tethered-eCG was. efficiently secreted and showed similar LH-like activity to the dimeric eCG. Interestingly, the FSH-like activity of the tethered-eCG was increased markedly in comparison with the native and wild type eCG. These results also suggest that this molecular can implay particular models of FSH-like activity not LH-like activity in the eCG/indicate that the constructs of tethered molecule will be useful in the study of mutants that affect subunit association and/or secretion. A single-chain analog can also be constructed to include additional hormone-specific bioactive generating potentially efficacious compounds that have only FSH-like activity. The LH/CG receptor (LH/CGR), a membrane glycoprotein that is present on testicular Leydig cells and ovarian theca, granulosa, luteal, and interstitial cells, plays a pivotal role in the regulation of gonadal development and function in males as well as in nonpregnant and pregnant females. The LH/CGR is a member of the family of G protein-coupled receptors and its structure is predicted to consist of a large extracellular domain connected to a bundle of seven membrane-spanning a-helices. The LH/CGR phosphorylation can be induced with a phorbol ester, but not with a calcium ionophore. The truncated form of LHR also was down-regulated normally in response to hCG stimulation. In contrast, the cell lines expressing LHR-t63I or LHR-628, the two phosphorylation-negative receptor mutant, showed a delay in the early phase of hCG-induced desensitization, a complete loss of PMA-induced desensitization, and an increase in the rate of hCG-induced receptor down-regulation. These results clearly show that residues 632-653 in the C-terminal tail of the LHR are involved in PMA-induced desensitization, hCG-induced desensitization, and hCG-induced down-regulation. Recently, constitutively activating mutations of the receptor have been identified that are associated with familial male-precocious puberty. Cells expressing LHR-D556Y bind hCG with normal affinity, exhibit a 25-fold increase in basal cAMP and respond to hCG with a normal increase in cAMP accumulation. This mutation enhances the internalization of the free and agonist-occupied receptors ~2- and ~17-fold, respectively. We conclude that the state of activation of the LHR can modulate its basal and/or agonist-stimulated internalization. Since the internalization of hCG is involved in the termination of hCG actions, we suggest that the lack of responsiveness detected in cells expressing LHR-L435R is due to the fast rate of internalization of the bound hCG. This statement is supported by the finding that hCG responsiveness is restored when the cells are lysed and signal transduction is measured in a subcellular fraction (membranes) that cannot internalize the bound hormone.

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Ginsenoside Rg1 attenuates cerebral ischemia-reperfusion injury due to inhibition of NOX2-mediated calcium homeostasis dysregulation in mice

  • Han, Yuli;Li, Xuewang;Yang, Liu;Zhang, Duoduo;Li, Lan;Dong, Xianan;Li, Yan;Qun, Sen;Li, Weizu
    • Journal of Ginseng Research
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    • v.46 no.4
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    • pp.515-525
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    • 2022
  • Background: The incidence of ischemic cerebrovascular disease is increasing in recent years and has been one of the leading causes of neurological dysfunction and death. Ginsenoside Rg1 has been found to protect against neuronal damage in many neurodegenerative diseases. However, the effect and mechanism by which Rg1 protects against cerebral ischemia-reperfusion injury (CIRI) are not fully understood. Here, we report the neuroprotective effects of Rg1 treatment on CIRI and its possible mechanisms in mice. Methods: A bilateral common carotid artery ligation was used to establish a chronic CIRI model in mice. HT22 cells were treated with Rg1 after OGD/R to study its effect on [Ca2+]i. The open-field test and poleclimbing experiment were used to detect behavioral injury. The laser speckle blood flowmeter was used to measure brain blood flow. The Nissl and H&E staining were used to examine the neuronal damage. The Western blotting was used to examine MAP2, PSD95, Tau, p-Tau, NOX2, PLC, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging was used to test the level of [Ca2+]i. Results: Rg1 treatment significantly improved cerebral blood flow, locomotion, and limb coordination, reduced ROS production, increased MAP2 and PSD95 expression, and decreased p-Tau, NOX2, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging results showed that Rg1 could inhibit calcium overload and resist the imbalance of calcium homeostasis after OGD/R in HT22 cells. Conclusion: Rg1 plays a neuroprotective role in attenuating CIRI by inhibiting oxidative stress, calcium overload, and neuroinflammation.

Development of Classification Model for hERG Ion Channel Inhibitors Using SVM Method (SVM 방법을 이용한 hERG 이온 채널 저해제 예측모델 개발)

  • Gang, Sin-Moon;Kim, Han-Jo;Oh, Won-Seok;Kim, Sun-Young;No, Kyoung-Tai;Nam, Ky-Youb
    • Journal of the Korean Chemical Society
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    • v.53 no.6
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    • pp.653-662
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    • 2009
  • Developing effective tools for predicting absorption, distribution, metabolism, excretion properties and toxicity (ADME/T) of new chemical entities in the early stage of drug design is one of the most important tasks in drug discovery and development today. As one of these attempts, support vector machines (SVM) has recently been exploited for the prediction of ADME/T related properties. However, two problems in SVM modeling, i.e. feature selection and parameters setting, are still far from solved. The two problems have been shown to be crucial to the efficiency and accuracy of SVM classification. In particular, the feature selection and optimal SVM parameters setting influence each other, which indicates that they should be dealt with simultaneously. In this account, we present an integrated practical solution, in which genetic-based algorithm (GA) is used for feature selection and grid search (GS) method for parameters optimization. hERG ion-channel inhibitor classification models of ADME/T related properties has been built for assessing and testing the proposed GA-GS-SVM. We generated 6 different models that are 3 different single models and 3 different ensemble models using training set - 1891 compounds and validated with external test set - 175 compounds. We compared single model with ensemble model to solve data imbalance problems. It was able to improve accuracy of prediction to use ensemble model.

Protective Effects of a Lycium chinense Ethanol Extract through Anti-oxidative Stress on Acute gastric lesion mice (급성 위염 유발 마우스 동물 모델에서 구기자(枸杞子) 에탄올 추출물의 위점막 손상 보호 효과)

  • Lee, AhReum;Lee, JooYoung;Kim, MinYeong;Shin, Mi-Rae;Shin, SungHo;Seo, BuIl;Kwon, OJun;Roh, Seong-Soo
    • The Korea Journal of Herbology
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    • v.30 no.6
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    • pp.63-68
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    • 2015
  • Objectives : Gastric lesions affect many people around the world and their development are results of the imbalance between destructive and protective factors in the gastric mucosa. Lycium chinense has been widely used as a traditional Korean medicine, it was recently reported that they have potent anti-inflammatory effects in chronic hepatitis models. Therefore, this study aimed to investigate the anti-inflammatory activity of Lycium chinense extract (LCE) on HCl-Ethanol induced gastric lesion mice.Methods : The ICR mice were divided randomly into five groups of six animals each. Group A was normal mice, and group B was treated orally with 0.5 ml 150 mM HCl-60% Ethanol. Mice in group C and D were pre-treatment of LCE (100 mg/kg and 200 mg/kg bodyweight, p.o before HCl/ethanol treatment) and group E was orally administered sucralfate (10 mg/kg).Results : 150mM HCl/60% ethanol-induced gastric mucosal injury mice were ameliorated mucosal damage upon histological evaluation by treatment of LCE. Pre-treatment of LCE attenuated reactive oxidative species (ROS) and produces peroxynitrite (ONOO-) in stomach tissues. As results of stomach protein analyses, LCE effectively reduce inflammatory-related factors such as cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6) in gastric lesion mice. In addition, nuclear factor kappa B (NF-κB) and inhibitor of phosphorylation of nuclear factor kappa B (p-IκB) were down-regulated in LCE-administrated gastric lesion mice.Conclusions : Our discovery supports that the therapeutic activity of LCE ameliorate the development of gastric lesion via suppressing the oxidative stress and gastric partial inflammation induced by 150 mM HCl/60% ethanol.

Soil Environmental Investigation of Plastic Film House in Chonnam Area (전남지역 시설재배 토양환경 실태조사)

  • Kim, Hee-Kwon;Park, In-Jin;Kim, Joung-Keun;Kim, Sang-Chul
    • Korean Journal of Soil Science and Fertilizer
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    • v.33 no.1
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    • pp.40-46
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    • 2000
  • The investigation and the analysis of soil chemical properties, microbial flora and cultural practices in plastic house of 60 farms (pepper 20, cucumber 20, oriental melon 20) were conducted in Chonnam area film. An amount of fertilizer application of farms was more than that of standard fertilizer application. That was phosphate at two and a half times, potassium at twice and manure at three times the amount of standard application. It was inferred that excessive fertilizer application would lead to salts accumulation in soil. Continuous cropping injury would be incurred by excesive salts accumulation in soil. Even if inorganic elements in soil culturing peppers, cucumbers and oriental melons were greater than optimum level, base-saturation degree of soil culturing peppers, cucumbers and oriental melons was 40:18:12, 55:16:14 and 40:27:11 respectively. That was lower than the optimum levels (60:15:5). Therefore, crops would be affected by uptake inhibition by nutrition imbalance. Density of Fusarium is related to plant decease in soil i.e. pepper $26.2{\times}10^2\;cfu\;g^{-1}$, cucumber $75.8{\times}10^2\;cfu\;g^{-1}$ and oriental melon $6.5{\times}10^2\;cfu\;g^{-1}$. B/F of soil planted with pepper, cucumber and oriental melon was 91.2, 80.4 and 18.8, respectively.

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Comparison of Korean Classification Models' Korean Essay Score Range Prediction Performance (한국어 학습 모델별 한국어 쓰기 답안지 점수 구간 예측 성능 비교)

  • Cho, Heeryon;Im, Hyeonyeol;Yi, Yumi;Cha, Junwoo
    • KIPS Transactions on Software and Data Engineering
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    • v.11 no.3
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    • pp.133-140
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    • 2022
  • We investigate the performance of deep learning-based Korean language models on a task of predicting the score range of Korean essays written by foreign students. We construct a data set containing a total of 304 essays, which include essays discussing the criteria for choosing a job ('job'), conditions of a happy life ('happ'), relationship between money and happiness ('econ'), and definition of success ('succ'). These essays were labeled according to four letter grades (A, B, C, and D), and a total of eleven essay score range prediction experiments were conducted (i.e., five for predicting the score range of 'job' essays, five for predicting the score range of 'happiness' essays, and one for predicting the score range of mixed topic essays). Three deep learning-based Korean language models, KoBERT, KcBERT, and KR-BERT, were fine-tuned using various training data. Moreover, two traditional probabilistic machine learning classifiers, naive Bayes and logistic regression, were also evaluated. Experiment results show that deep learning-based Korean language models performed better than the two traditional classifiers, with KR-BERT performing the best with 55.83% overall average prediction accuracy. A close second was KcBERT (55.77%) followed by KoBERT (54.91%). The performances of naive Bayes and logistic regression classifiers were 52.52% and 50.28% respectively. Due to the scarcity of training data and the imbalance in class distribution, the overall prediction performance was not high for all classifiers. Moreover, the classifiers' vocabulary did not explicitly capture the error features that were helpful in correctly grading the Korean essay. By overcoming these two limitations, we expect the score range prediction performance to improve.

Expression of Caspase 3, Survivin, and p53 Protein in Urethane Induced Mouse Lung Carcinogenesis (Urethane으로 유발된 생쥐 폐샘암종 발생과정에서 Caspase 3, Survivin과 p53 단백 발현)

  • Shin, Jong Wook;Lee, Soo Hwan;Park, Eon Sub
    • Tuberculosis and Respiratory Diseases
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    • v.63 no.3
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    • pp.251-260
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    • 2007
  • Purpose: An imbalance of cell proliferation and cell apoptosis is an important mechanism in carcinogenesis. Capase 3, survivin and p53 have been identified as important members of the apoptotic related proteins. This study evaluated the proliferating cell nuclear antigen(PCNA), apoptosis, apoptotic related protein such as capase 3, survivin and p53 using urethane-induced mouse lung carcinogenesis, which provides reproducible steps from hyperplasia to adenocarcinoma. Methods: Urethane was administered to the ICR mice through an intra-peritoneal injection, The mice were sacrificed at 5, 15, and 25 weeks after urethane intervention. The sequential morphological changes and immunohistochemical expression of PCNA, apoptosis, capase 3, survivin, and p53 were examined during mouse lung carcinogenesis. Results: During carcinogenesis, the sequential histological changes were observed from hyperplasia of type II pneumocytes, to anadenoma, and ultimately to an overt adenocarcinoma. The PCNA Labeling index (LI) was 9.6% in hyperplasia, 23.2% in adenoma, and 55.7% in adenocarcinoma, respectively. The apoptotic LI was 0.24% in hyperplasia, 1.25% in adenoma, and 5.27% in adenocarcinoma. A good correlation was observed between the PCNA LI and apoptotic LI. The expression of caspase 3 was remarkable- i.e., 46.7% in adenocarcinoma, in contrast to 15% in hyperplasia and 16% in adenoma. Survivin was detected weakly in the alveolar hyperplasia and showed an increasing expressional pattern in adenoma and adenocarcinoma. p53 expression was detected only in the adenocarcinoma lesions with an expression rate of 13.3%. The level of caspase 3 expression correlated with the increase in the apoptotic index. The positive expression of caspase 3 was associated with an increased apoptotic index. Conclusions: These results suggest that the PCNA LI and apoptotic LI might be useful markers for evaluating the risk of a malignant transformation. In addition, caspase, survivin and p53 might play a role in the early and late steges of urethane-induced mouse lung carcinogenesis.

The Budget of Nutrients in the Estuaries Near Mokpo Harbor (목포항 주변 하구역의 영양염 수지)

  • Kim, Yeong-Tae;Choi, Yoon-Seok;Cho, Yoon-Sik;Oh, Hyun-Taik;Jeon, Seung-Ryul;Choi, Yong Hyeon;Han, Hyoung-Kyun
    • Journal of the Korean Society of Marine Environment & Safety
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    • v.22 no.6
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    • pp.708-722
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    • 2016
  • Land-Ocean Interactions in the Coastal Zone (LOICZ) models for nutrient budgets were used to estimate the seasonal capacity of the Youngsan Estuary and Youngam-Geumho Estuary to sink and/or supply nutrients such as dissolved inorganic phosphorus (DIP) and nitrogen (DIN) to provide an understanding of the behavior of the coupled biogeochemical cycles of phosphorus and nitrogen in the estuaries (Youngsan Estuary, Youngam-Geumho Estuary) near Mokpo Harbor. During non-stratified periods (May, September, and November, 2008), simple three-box models were applied in each sub-region of the system, while a two-layer box model was applied during on-site observation of stratification development (July, 2008). The resulting mass-balance calculation indicated that even after large discharges from artificial lakes (in May and July), DIP influxes due to a mixing exchange ($V_{X-3}$, or $V_{deep}$) were more than terrigenous loads, indicating the backward transportation of nutrients from a marine source. The model results also indicated that for nutrient loads (DIP and DIN fluxes) in September, an extreme congestion of nutrients occurred around the mouths (sub-region III of the model) of the estuaries, possibly due to an imbalance in physical circulations between the estuaries and offshore locations. In November, the Youngam-Geumho Estuary, into which freshwater was discharged from artificial lakes (Youngam and Geumho Lake), showed nutrient enrichment in the water column, but the Youngsan Estuary showed nutrient depletion. In conclusion, to efficiently control water quality in the estuaries near Mokpo Harbor, integrated environmental management programs should be implemented. I.e., the reduction of nutrient loads from land basins as well as the deposit of nutrient loads into adjacent coastal lines.

A Study on the Increase of Dental Technicians in Korea and the Regional Distribution of the Korea Dental Technician Association Members (우리나라 치과기공사의 증가현황 및 협회원의 지역별 분포현황 연구)

  • Kwon, Soon-Seog
    • Journal of Technologic Dentistry
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    • v.26 no.1
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    • pp.9-34
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    • 2004
  • The present study reviews the license registration status of dental technicians and dentists from 1970 to 2002, the number of technician members of The Korea Dental Technician Association from 1990 to 2003, and the number of dentist members in 2003. It also considers the yearly membership fluctuations, its growth rates, yearly increase/decrease, the rate of dentist to dental technician, regional distribution of association members, regional yearly increase/decrease of the members, and the regional distribution of dentists and dental technicians. The purpose is to identify and predict the problems in the demand/supply of dental technicians and the regional imbalance of manpower distribution. By doing so, this study attempts to propose the appropriate standard for the supply of dental technicians and point out the necessity of making mid- or long-term plans for ensuring the efficiency of manpower supply and balanced regional distribution. The result is as follows: 1. The number of dental technicians and dentists in 2002 has grown 36.79 and 9.27 times from 1970, and 2.20 and 2.05 times from 1990, respectively. It tool 11 years for the twofold increase of dental technicians from 1990, one year faster than the same increase of dentists. The number of dental technicians per a dentist was the lowest in 1972 (0.21 person), and the highest in 2002 (0.86 person). Specifically, the fastest growth was observed for a year from 1983 (0.47 technician per a dentist) to 1984 (0.6). From 1984 to 1986, the ratio grew by 0.1 every year. Summing up the numbers of dentists and dental technicians who passed the national certification examination, this study predicted the number of dental technicians per a dentist to be 0.88 in 2003, and 0.90 in 2004. 2. From 1990 to 2003, the average distribution of dental technician was 71.76% in the metropolitan areas and 28.24% in other smaller regions. The proportion of dental technicians working in the three major cities (Seoul, Busan, and Daegu) was the lowest in 2001 (52.39%) and the highest in 1996 (62.66%). The majority number of dental technicians who practiced in the metropolitan areas (about 70% of the entire population) were in service in the three major cities. 3. Compared with 1990, the number of dental technicians in 2003 grew 2.28 times in the large cities, and 2.05 times in other smaller regions. The yearly growth rate was the highest in 1994 over the previous year: 26.06% in large cities and 17.86% in the other regions. In the large metropolitan cities, the growth rate was the highest in Incheon (5.8 times for 5 years from 1998 to 2003), In the rest of the regions, the increase of dental technicians was the highest in Gyeonggi (6.5 times from 1990 to 2003). 4. In 2003, as much as 73.40% of all the members of the Korea Dental Technician Association were distributed in the large metropolitan cities, and the rest 26.60% were in other smaller regions. Meanwhile, 54.35% of the dentists practiced in the metropolitan cities, and the rest 45.65% were in service at other regions. This result indicates that more dental technicians than dentists are concentrated in large cities. More than half of all the technician members of the Association are distributed in the three major cities (i.e. Seoul, Busan, Daegu). On the other hand, 42.03% of dentist members are in these three cities and 53.97% of them practice in Seoul, Gyeonggi, and Busan. In 2003, the ratio of dentist to dental technician is 1:0.43 in general, while the ratio is 1:0.58 in the metropolitan cities, and 1:0.43 in other regions. In 2003, 33.30% of all the certified dental technicians are the member of the Korea Dental Technician Association, while 66.82% of all the licensed dentists are its members.

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Comparative Volume Measuring Methods According to the Tumor Characters in PET/CT (PET/CT 검사에서 종양의 특성에 따른 체적 측정 방법 비교)

  • Choi, Yong Hoon;Ban, Yung Gak;Oh, Shin Hyun;Lim, Han Sang;Kim, Jae Sam
    • The Korean Journal of Nuclear Medicine Technology
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    • v.20 no.1
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    • pp.52-58
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    • 2016
  • Purpose Recent retrospective studies are being actively conducted to analyze the survival of patients with SUVmax, MTV, TLG, such as information from a variety of PET originating. However, there is no clear way is difficult to accurately measure the volume of the tumor may be the difference between the caster is raised. In this study, to evaluate compare the volume measuring methods according to the characteristics of the tumor. Materials and Methods 18F-saline to fill the NEMA IEC Body Phantom insert the volume of balance and imbalance in phantom were acquired to the Biograph truepoint 40 (Siemens medical system, Germany) PET/CT scanner. The ratio of the volume and Background was acquired as 3.0, 5.0, 8.0, 18, 40. Clinical patients were randomly selected 120 people in staging patients with cancer of the digestive system from the year 2010 until the year 2014. Measurement methods were used a 40% threshold, 50% threshold and gradient segmentation technique, i.e. PET EDGE. Five years of experience of the two radio-technologist and one doctor was measured by repeated three times. Analysis methods were Intraclass correlation coefficient and Pearson correlation. Results In Phantoms, the 40% threshold method gave the best concordance between measured and actual volumes (r = 0.992, 0.997). In clinical patient outcome agreement between observers EDGE it is as high as 0.999 (CI: 0.998-0.999). And there were no statistical significance of the difference between the measurements (P = 0.620). 40% threshold method showed the best correlation between the measurements (r = 0.953). Increasing the ratio of tumor to background decreased the influence of a measuring method. Conclusion How to measure volume of the tumor in the patient was clinically most useful is 50% and the lowest impact on the characteristics of the tumor. Therefore, to reduce the background of the patients in PET/CT scan, it should be required research and effort.

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