• 제목/요약/키워드: Reduced mechanism

검색결과 2,190건 처리시간 0.027초

Chronic kisspeptin delays puberty and reduces feed intake and body weight in female rats

  • Sathagopam, Sriravali;Ullewar, Meenal Prabhakar;Harne, Rakhi;Velmurugan, Sathya
    • 한국동물생명공학회지
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    • 제36권1호
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    • pp.25-34
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    • 2021
  • Kisspeptin is a key player in the central control of reproductive axis. Central administration of kisspeptin has been shown to advance puberty in rats. Stimulation of hypothalamic GnRH pulse generating mechanism by kisspeptin has been proposed to be the mechanism behind the onset of puberty. We hypothesized that chronic high doses of kisspeptin administration suppresses the reproductive axis and hence delays the pubertal onset. Hence, we investigated the effect of peripheral administration of chronic high doses of kisspeptin on pubertal onset, feed intake and body weight in female rats. Rats were treated with saline or kisspeptin (100 nmoles per day; intraperitoneal) for 26 days (day 25 to day 50 postnatal) and the day of vaginal opening was marked as day of puberty. Kisspeptin treated rats had delayed pubertal onset and reduced feed intake and body weight. Gonadal GPR54 mRNA was reduced suggesting that chronic high doses of kisspeptin may suppress the reproductive functions possibly by downregulation of GPR54 receptor. However, delay in puberty due to reduction in feed intake and body weight could not be ruled out in this study. Further, our study emphasizes the importance of dosage and duration of kisspeptin administration in the manipulation of reproductive axis. Our study, for the first time, suggests that kisspeptin and its analogues, if proven beneficial, could be used to treat precocious puberty in children. It appears that, though a promising tool for enhancing fertility, kisspeptin acts as a double-edged sword and has to be cautiously used to manipulate reproduction.

대황목단탕의 메티실린 내성 황색 포도상구균에 대한 항균활성 (The Antimicrobial Activity of Daehwangmokdan-tang against Methicillin-resistant Staphylococcus aureus)

  • 한형선;권동렬;강옥화
    • 대한본초학회지
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    • 제35권3호
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    • pp.47-54
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    • 2020
  • Objective : Infectious diseases are a growing problem worldwide by Methicillin-resistant Staphylococcus aureus (MRSA). Daehwangmokdan-tang is one of the oriental medicine prescriptions contained in Principles and Practice of Eastern Medicine. This study investigated the antibacterial activity of EtOH 70% extracts of Daehwangmokdan-tang (DMT) which prescription is composed of oriental medicine against MRSA. Methods : The antimicrobial activity and active concentration of MRSA were verified by measuring the minimum inhibitory concentration (MIC) of DMT. In addition, the effects of the disease were checked by treating the existing antibiotics and large ethanol extract in parallel, and the extent of growth suppression was checked over time. In addition, cell membrane permeability experiment confirmed the effect of large DMT on the immunity mechanism of MRSA. Results : TThe minimum inhibitory concentration of DMT against MRSA is 500 ~ 2000 ㎍/㎖ by broth dilution method. In the checkerboard method, the combinations of DMT with antibiotics has partial synergistic effect or synergy effect and DMT markedly reduced the MICs of the antibiotics oxacillin (OX), gentamicin (GEN) against MRSA. In the inhibition of resistance mechanism of DMT against MRSA, the expression of resistance gene and protein about β-lactam antibiotic was reduced. Also, we observed the effect of DMT about cell membrane permeability against MRSA, and confirmed that DMT suppressed growth of strains by increasing cell membrane permeability and energy metabolism. Conclusion : Basis on the result, we speculate that DMT may be useful for the treatment of MRSA infections when used in combination with β-lactam antibiotic.

Kalkitoxin attenuates calcification of vascular smooth muscle cells via RUNX-2 signaling pathways

  • Saroj K Shrestha;Se-Woong Kim;Yunjo Soh
    • Journal of Veterinary Science
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    • 제24권5호
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    • pp.69.1-69.11
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    • 2023
  • Background: Kalkitoxin (KT) is an active lipopeptide isolated from the cyanobacterium Lyngbya majuscula found in the bed of the coral reef. Although KT suppresses cell division and inflammation, KT's mechanism of action in vascular smooth muscle cells (VSMCs) is unidentified. Therefore, our main aim was to investigate the impact of KT on vascular calcification for the treatment of cardiovascular disease. Objectives: Using diverse calcification media, we studied the effect of KT on VSMC calcification and the underlying mechanism of this effect. Methods: VSMC was isolated from the 6 weeks ICR mice. Then VSMCs were treated with different concentrations of KT to check the cell viability. Alizarin red and von Kossa staining were carried out to examine the calcium deposition on VSMC. Thoracic aorta of 6 weeks mice were taken and treated with different concentrations of KT, and H and E staining was performed. Real-time polymerase chain reaction and western blot were performed to examine KT's effect on VSMC mineralization. Calcium deposition on VSMC was examined with a calcium deposition quantification kit. Results: Calcium deposition, Alizarin red, and von Kossa staining revealed that KT reduced inorganic phosphate-induced calcification phenotypes. KT also reduced Ca++-induced calcification by inhibiting genes that regulate osteoblast differentiation, such as runtrelated transcription factor 2 (RUNX-2), SMAD family member 4, osterix, collagen 1α, and osteopontin. Also, KT repressed Ca2+-induced bone morphogenetic protein 2, RUNX-2, collagen 1α, osteoprotegerin, and smooth muscle actin protein expression. Likewise, Alizarin red and von Kossa staining showed that KT markedly decreased the calcification of ex vivo ring formation in the mouse thoracic aorta. Conclusions: This experiment demonstrated that KT decreases vascular calcification and may be developed as a new therapeutic treatment for vascular calcification and arteriosclerosis.

등가 스트럿 모델에 의한 리브 보강 RBS 철골모멘트접합부의 내진설계 (Seismic Design of Rib-Reinforced RBS (Reduced Beam Section) Steel Moment Connections Based on Equivalent Strut Model)

  • 이철호
    • 한국강구조학회 논문집
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    • 제13권5호
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    • pp.493-502
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    • 2001
  • 본 연구에서는 아직 설계법이 정립되지 않은 리브로 보강된 RBS 철골모멘트 접합부의 내진설계법을 등가 스트럿 모델에 의거하여 제시하였다. 종종 엔지니어가 리브를 사용하여 철골모멘트접합부의 내진성능을 높이고자 할 경우 고전 휨이론에 의거하여 리브와 보로 구성된 일체단면의 단면2차모멘트로서 그루브 용접부의 인장응력도 예측하려 하는데 이는 타당치 않다. 리브접합부의 응력전달 메커니즘은 고전 휨이론에 의한 메카니즘과는 전혀 다르다. 즉 리브는 고전 휨이론에 의한 기대와는 달리 리브의 대각선 기울기 방향으로 스트럿 거동을 보인다. 필자는 이 같은 점에 주목하여 리브를 스트럿 요소로 파악하여 리브 접합부의 설계에 활용될 수 있는 등가 스트럿 모델을 이미 제시한 바가 있다. 본 연구에서는 이 등가 스트럿 모델을 기초로 리브접합부의 실용설계에 활용될 수 있는 단계별 설계절차를 제안하였다.

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Synergistic Effect of Ethaselen and Selenite Treatment against A549 Human Non-small Cell Lung Cancer Cells

  • Xu, Wei;Ma, Wei-Wei;Zeng, Hui-Hui
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권17호
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    • pp.7129-7135
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    • 2014
  • Background: In this study, we aimed to evaluate the growth inhibitory effect of the combination of ethaselen (BBSKE) and low fixed dose of selenite against A549 human non-small cell lung cancer cells in vitro. Materials and Methods: Growth inhibitory effects against A549 cells were determined by SRB assay. Combination index (CI) values were calculated based on Chou-Talalay median-effect analyses. Dose reduction index (DRI) values were applied to calculate dose reduction of selenite. Contents of free thiols and GSH were determined by DTNB assay and intracellular ROS levels by DCFH-DA fluorescence labeling. Results: Compared with BBSKE or selenite single treatment, the combined application of ethaselen and a low fixed dose of selenite shortened the onset time of sodium selenite, reduced $IC_{50}$ values, and increased the maximum inhibition rates, suggesting a possible molecular mechanism of the synergism. Obvious synergistic effects were observed after different times of combination treatment, especially after 24 h. Compared with selenite single treatment, dosage of selenite could be remarkably reduced in combination therapy to gain the same inhibitory effect on cell proliferation. Compared with BBSKE single treatment, the content of free thiols and GSH were significantly reduced and ROS levels greatly elevated in the combination group. For the combination treatment, cell viability increased as greater concentrations of GSH were added. Conclusions: All these results indicate that the combination treatment of BBSKE and selenite showed synergism to inhibit A549 cell proliferation in vitro, and also reduced the selenite dosage to mitigate its toxicity which is very meaningful for combination chemotherapy of lung cancer. The synergism was probably caused by the accelerated exhaustion of intracellular reductive substances, such as free thiols and GSH, which ultimately leads to enhanced oxidative stress and apoptosis.

가미대강활탕(加味大羌活湯)이 Collagen II로 유발된 관절염에 미치는 영향 (Inhibitory Effects of Gamidaeganghwal-tang(Jiaweidaqianghuo-tang) on Rheumatoid Arthritis Induced by Type II Collagen)

  • 김민기;오민석
    • 한방재활의학과학회지
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    • 제19권2호
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    • pp.89-102
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    • 2009
  • Objectives : This study was carried out to understand the immunity responses and anti-oxidation effect of the Gamidaeganghwal-tang(GDT) on rheumatoid arthritis by using the THP-1 cells and the serum of CIA mice. Methods : For this purpose, GDT was orally administerd to mice with rheumatoid arthritis induced by collagen II. To investigate the immunity responses, value of cytokine and gene expression in the THP-1 cell, levels of cytokines in the serum of CIA(collagen type II induced arthritis) mice, number of immunocyte in PBMC of CIA mice were measured. Then, anti-oxidant activity, scavenging activity on DHHP(2,2-diphenyl-1-picrylhydrazyl) free radical and SOD(Superoxide dismutae)-like activity of GDT was observed. Results : 1. The levels of IL-$1{\beta}$, IL-6, IL-8, MCP-1 at 100, $50{\mu}g/m{\ell}$ of GDT were significantly reduced in the THP-1 cell. 2. The levels of TNF-${\alpha}$, COX-2 mRNA expression at 100, $50{\mu}g/m{\ell}$ of GDT and IL-$1{\beta}$, IL-6 at $100{\mu}g/m{\ell}$ of GDT were significantly reduced in the THP-1 cell line. 3. The levels of IL-6, TNF-${\alpha}$ and IL-$1{\beta}$ were significantly reduced in the serum of CIA mice. 4. The absolute number of CD3+, CD4+ and CD8+ cells were significantly induced, CD3+/CD69+, CD3+/CD49+, CD19+, B220+/CD23+ cells were significantly reduced in PBMC. 5. Scavenging activity on DPPH free radical and SOD-like activity were significantly induced in a concentration dependent manner. Conclusions : Taking all these observations, GDT considered to be effective in treating rheumatoid arthritis. Therefore we have to survey continuously in looking for the effective substance and mechanism in the future.

축약법에 의한 구조물 결합부의 동적 거동 예측 (Dynamical Predictions of the Structural Connection by the Reduced Approach)

  • 윤성호
    • 한국전산구조공학회논문집
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    • 제27권6호
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    • pp.589-596
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    • 2014
  • 기계 구조물에서 부재의 결합부가 시스템 전체의 동적 거동에 매우 심각한 영향을 미치고 있다. 따라서 동적인 응답의 정확한 예측은 이러한 결합부를 어떻게 모델링 하느냐에 달려 있다고 해도 과언이 아니다. 본 논문에서는 결합부의 유연성을 정량적으로 표현하기 위하여 서로 대칭이고 마주보는 외팔보의 중앙에 선형 및 비틀림 스프링을 결합부에 이식하였다. 이를 바탕으로 결합부의 강성 변화에 따른 시스템의 재해석은 축약법과 유한요소법으로 계산하였다. 이항 급수로 표현되는 기저 벡터의 수에 따라서 전체 모델의 크기는 획기적으로 감소되어 축약 모델로 매우 짧은 시간에 효율적으로 계산할 수 있었다. 본 연구에서는 두 가지 경우의 수치해석 예가 제시되어 축약 모델의 결과가 정밀해와 잘 일치함을 보여주고 있다.

Heat stress on microbiota composition, barrier integrity, and nutrient transport in gut, production performance, and its amelioration in farm animals

  • Patra, Amlan Kumar;Kar, Indrajit
    • Journal of Animal Science and Technology
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    • 제63권2호
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    • pp.211-247
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    • 2021
  • Livestock species experience several stresses, particularly weaning, transportation, overproduction, crowding, temperature, and diseases in their life. Heat stress (HS) is one of the most stressors, which is encountered in livestock production systems throughout the world, especially in the tropical regions and is likely to be intensified due to global rise in environmental temperature. The gut has emerged as one of the major target organs affected by HS. The alpha- and beta-diversity of gut microbiota composition are altered due to heat exposure to animals with greater colonization of pathogenic microbiota groups. HS also induces several changes in the gut including damages of microstructures of the mucosal epithelia, increased oxidative insults, reduced immunity, and increased permeability of the gut to toxins and pathogens. Vulnerability of the intestinal barrier integrity leads to invasion of pathogenic microbes and translocation of antigens to the blood circulations, which ultimately may cause systematic inflammations and immune responses. Moreover, digestion of nutrients in the guts may be impaired due to reduced enzymatic activity in the digesta, reduced surface areas for absorption and injury to the mucosal structure and altered expressions of the nutrient transport proteins and genes. The systematic hormonal changes due to HS along with alterations in immune and inflammatory responses often cause reduced feed intake and production performance in livestock and poultry. The altered microbiome likely orchestrates to the hosts for various relevant biological phenomena occurring in the body, but the exact mechanisms how functional communications occur between the microbiota and HS responses are yet to be elucidated. This review aims to discuss the effects of HS on microbiota composition, mucosal structure, oxidant-antioxidant balance mechanism, immunity, and barrier integrity in the gut, and production performance of farm animals along with the dietary ameliorations of HS. Also, this review attempts to explain the mechanisms how these biological responses are affected by HS.

Ofloxacin Resistance Mechanism in PA150 and PA300-Clinical Isolates of Pseudomonas aeruginosa in Korea

  • Lee, Soon-Deuk;Lee, Yeon-Hee
    • Archives of Pharmacal Research
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    • 제21권6호
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    • pp.671-676
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    • 1998
  • Five hundred and seventy clinical strains of Pseudomonas aeruginosa were isolated from August 1993 to August 1994 in Korea and screened for their resistance to ciprofloxacin, norfloxacin, and ofloxacin. Among these, two P. aeruginosa strains (PA150 and PA300) were selected based on their strong resistance (MICs > 50mcg/ml) to all three quinolones. The susceptible strain as well as two resistant strains had proton gradient-dependent efflux system. Efflux system in PA300 showed different specificities to ofloxacin and ciprofloxacin while PA150 had less permeability for ofloxacin. Ofloxacin had a less inhibitory action on DNA synthesis in permeabilized cells of PA150 and PA300 than 1771M. When quinolone resistance determining region (QRDR) in gyrA was sequenced, PA300 had one missense mutation, Asn 116Tyr, which was newly reported in this work. The results showed that PA150 became ofloxacin resistant by reduced ofloxacin accumulation due to the existence of efflux system and low permeability, while resistance of PA300 was due to the efflux system and a mutation in QRDR of gyrA -the target site of quinolone.

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Effect of Orally Administered Branched-chain Amino Acids on Protein Synthesis and Degradation in Rat Skeletal Muscle

  • Yoshizawa, Fumiaki;Nagasawa, Takashi;Sugahara, Kunio
    • Asian-Australasian Journal of Animal Sciences
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    • 제18권1호
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    • pp.133-140
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    • 2005
  • Although amino acids are substrates for the synthesis of proteins and nitrogen-containing compounds, it has become more and more clear over the years that these nutrients are also extremely important as regulators of body protein turnover. The branched-chain amino acids (BCAAs) together or simply leucine alone stimulate protein synthesis and inhibit protein breakdown in skeletal muscle. However, it was only recently that the mechanism(s) involved in the regulation of protein turnover by BCAAs has begun to be defined. The acceleration of protein synthesis by these amino acids seems to occur at the level of peptide chain initiation. Oral administration of leucine to food-deprived rats enhances muscle protein synthesis, in part, through activation of the mRNA binding step of translation initiation. Despite our knowledge of the induction of protein synthesis by BCAAs, there are few studies on the suppression of protein degradation. The recent findings that oral administration of leucine rapidly reduced $N^{\tau}$-methylhistidine (3-methylhistidine; MeHis) release from isolated muscle, an index of myofibrillar protein degradation, indicate that leucine suppresses myofiblilar protein degradation. The details of the molecular mechanism by which leucine inhibits proteolysis is just beginning to be elucidated. The purpose of this report was to review the current understanding of how BCAAs act as regulators of protein turnover.