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Anti-inflammatory Effect of Morinda citrifolia on LPS-induced Inflammation in RAW 264.7 Cells Through the JAK/STAT Signaling Pathway (JAK/STAT 신호전달 경로를 통한 LPS 유도 RAW 264.7 세포의 염증에 대한 노니의 항염증 효과)

  • Jo, Beom Gil;Bang, In Seok
    • Journal of Life Science
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    • v.32 no.2
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    • pp.125-134
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    • 2022
  • This study investigated whether or not the major bioactive compounds of Noni (Morinda citrifolia) are involved in anti-inflammatory activity through the JAK/STAT upper signaling pathway in RAW 264.7 cells. The experimental results show that the M. citrifolia ethyl acetate fraction (Mc-EtOAc) obtained by sequential fractionation with organic solvents from the plant's dried fruits exhibits the highest antioxidant activity. In addition, the cytoprotective effects of Mc-EtOAc against H2O2-induced oxidative stress in the RAW 264.7 cells suppressed cytotoxicity in a dose-dependent manner. The group pretreated with Mc-EtOAc at a concentration of 240 ㎍/ml showed higher cell viability of 84.5%, compared to 71.6% in the LPS-treated group, and LPS-induced NO production decreased to half the amount in the positive control group. Mc-EtOAc treatment also led to a significant dose-dependent reduction in iNOS expression. Although COX-2 expression was increased by 300% following LPS induction, it was significantly decreased in a dose-dependent manner by pretreatment with Mc-EtOAc at concentrations of 120 and 240 ㎍/ml. An inhibition of the mRNA expression of pro-inflammatory cytokines IL-1β and TNF-α was observed. The investigation also revealed that the phosphorylation levels of pJAK1 and pSTAT3 in LPS-induced RAW 264.7 cells were significantly reduced by Mc-EtOAc treatment.

Impact of concurrent inspiratory muscle and aerobic exercise training on pulmonary function and cardiopulmonary responses (흡기근육 훈련과 유산소운동의 동시적용이 심폐반응과 폐기능에 미치는 영향)

  • Jung, H.J.;Lee, D.T.
    • Exercise Science
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    • v.21 no.3
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    • pp.373-384
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    • 2012
  • The effects of inspiratory muscle training in conjunction with aerobic exercise on inspiratory muscle strength, pulmonary function, and maximal oxygen uptake(VO2max) were examined. Twenty four healthy collegiate men were divided into three groups; respiratory muscle training group(RTG; n=8), running exercise group(REG; n=8), and both respiratory muscle training and running group(BTG; n=8). Their pulmonary function, maximal inspiratory pressures(PImax), and VO2max were assessed before and after intervention. RTG underwent inspiratory muscle training(IMT) with load set to 50 % of PImax, 30 times per session, twice a day, 4 days a week REG ran on a treadmill at 70-75 % of VO2max for 30 min a day, 4 days a week. BTG participated both IMT and the running exercise. Participant's anthropometric parameters and pulmonary function were not changed. VO2max increased by 6.1±3.3 %, 5.9±6.6 %, and 10.0±8.3 % in RTG, REG, and BTG, respectively(p< .05), and PImax also increased by 21.7±14.3 %, 19.7±12.0 %, and 27.0±12.1 % in RTG, REG, and BTG, respectively, but no group differences were found. Based on the study, although statistically insignificant, BTG showed the biggest increase of VO2max and PImax indicating a possible synergic effect of inspiratory muscle training and aerobic exercise on respiratory responses.

Molecular Signatures in Chicken Lungs Infected with Avian Influenza Viruses

  • Jeong Woong Park;Marc Ndimukaga;Jaeyoung Heo;Ki-Duk Song
    • Korean Journal of Poultry Science
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    • v.50 no.4
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    • pp.193-202
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    • 2023
  • Influenza IAVs are encapsulated negative-strand RNA viruses that infect many bird species' respiratory systems and can spread to other animals, including humans. This work reanalyzed previous microarray datasets to identify common and specific differentially expressed genes (DEGs) in chickens, as well as their biological activities. There were 760 and 405 DEGs detected in HPAIV and LPAIV-infected chicken cells, respectively. HPAIV and LPAIV have 670 and 315 DEGs, respectively, with both viruses sharing 90 DEGs. Because of HPAIV infection, numerous genes were implicated in a fundamental biological function of the cell cycle, according to the functional annotation of DEGs. Of the targeted genes, expressions of CDC Like Kinase 3 (CLK3), Nucleic Acid Binding Protein 1 (NABP1), Interferon-Inducible Protein 6 (IFI6), PIN2 (TERF1) Interacting Telomerase Inhibitor 1 (PINX1), and Cellular Communication Network Factor 4 (WISP1) were altered in DF-1 cells treated with polyinosinic:polycytidylic acid (PIC), a toll-like receptor 3 (TLR3) ligand, suggesting that transcription of these genes be controlled by TLR3 signaling. To gain a better understanding of the pathophysiology of AIVs in chickens, it is crucial to focus more research on unraveling the mechanisms through which AIV infections may manipulate host responses during the infection process. Insights into these mechanisms could facilitate the development of novel therapeutic strategies.

EFFECT OF OCTANOL, THE GAP JUNCTION BLOCKER, ON THE REGULATION OF FLUID SECRETION AND INTRACELLULAR CALCIUM CONCENTRATION IN SALIVARY ACINAR CELLS (흰쥐 악하선 세포에서 gap junction 봉쇄제인 octanol이 타액분비 및 세포내 $Ca^{2+}$ 농도 조절에 미치는 영향)

  • Lee, Ju-Seok;Seo, Jeong-Taeg;Lee, Syng-Il;Lee, Jong-Gap;Sohn, Heung-Kyu
    • Journal of the korean academy of Pediatric Dentistry
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    • v.26 no.2
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    • pp.399-415
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    • 1999
  • From bacteria to mammalian cells, one of the most important mediators of intracellular signal transduction mechanisms which regulate a variety of intracellular processes is free calcium. In salivary acinar cells, elevation of intracellular calcium concentration ($[Ca^{2+}]_i$) is essential for the salivary secretion induced by parasympathetic stimulation. However, in addition to $[Ca^{2+}]_i$, gap junctions which couple individual cells electrically and chemically have also been reported to regulate enzyme secretion in pancreatic acinar cells. Since the plasma membrane of salivary acinar cells has a high density of gap junctions, and these cells are electrically and chemically coupled with each other, gap junctions may modulate the secretory function of salivary glands. In this respect, I planned to investigate the role of gap junctions in the modulation of salivary secretion and $[Ca^{2+}]_i$, using mandibular salivary glands of rats. In order to measure the salivary flow rate, fluid was collected from the cannulated duct of the isolated perfused rat mandibular glands at 2 min intervals. $[Ca^{2+}]_i$, was measured from the cells loaded with fura-2 by spectrofluorometry. The results obtained were as follows: 1. CCh-induced salivary secretion was reversibly inhibited by 1 mM octanol, a gap junction blocker. 2. CCh-induced increase in $[Ca^{2+}]_i$, was also reversed by the application of 1 mM octanol. 3. Octanol did not block the initial increase in $[Ca^{2+}]_i$ caused by CCh, which suggested that the reduction of $[Ca^{2+}]_i$, caused by gap junction blockade was not resulted from the inhibition of $Ca^{2+}$ release from intracellular $Ca^{2+}$ stores. 4. Addition of octanol during stimulation with $1{\mu}M$ thapsigargin, a potent microsomal ATPase inhibitor, reduced $[Ca^{2+}]_i$, to the basal level. This suggested that inhibition of gap junction permeability closed plasma membrane $Ca^{2+}$ channels. 5. 2,5-di-tert-butyl-1,4-benzohydroquinone (TBQ) generated $[Ca^{2+}]_i$ oscillations resulting from periodic influx of $Ca^{2+}$ via plasma membrane. The TBQ-induced $[Ca^{2+}]_i$ oscillations were stopped by the application of 1mM octanol which implicated that gap junctions modulate the permeability of plasma membrane $Ca^{2+}$ channels. 6. Glycyrrhetinic acid, another well known gap junction blocker, also inhibited CCh-induced salivary secretion from rat mandibular glands. These results suggested that gap junctions play an important role in the modulation of fluid secretion from the rat mandibular glands and this was probably due to the inhibition of $Ca^{2+}$ influx through the plasma membrane $Ca^{2+}$ channels.

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Effect of Repetitive Transcranial Magnetic Stimulation in Drug Resistant Depressed Patients (치료 저항성 우울증 환자에서 반복적 경두개 자기자극후 국소뇌혈류 변화)

  • Chung, Yong-An;Yoo, Ie-Ryung;Kang, Bong-Joo;Chae, Jeong-Ho;Lee, Hye-Won;Moon, Hyun-Jin;Kim, Sung-Hoon;Sohn, Hyung-Sun;Chung, Soo-Kyo
    • Nuclear Medicine and Molecular Imaging
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    • v.41 no.1
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    • pp.9-15
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    • 2007
  • Purpose: Repetitive transcranial magnetic stimulation (rTMS) has recently been clinically applied in the treatment of drug resistant depressed patients. There are mixed findings about the efficacy of rTMS on depression. Furthermore, the influence of rTMS on the physiology of the brain is not clear. We prospectively evaluated changes of regional cerebral blood flow (rCBF) between pre- and post-rTMS treatment in patients with drug resistant depression. Materials and Methods: Twelve patients with drug-resistant depression (7 male, 5 female; age range: $19{\sim}52$ years; mean age: $29.3{\pm}9.3$ years) were given rTMS on right prefrontal lobe with low frequency (1 Hz) and on left prefrontal lobe with high frequency (20 Hz), with 20-minute-duration each day for 3 weeks. Tc-99m ECD brain perfusion SPECT was obtained before and after rTMS treatment. The changes of cerebral perfusion were analyzed using statistical parametric mapping (SPM; t=3.14, uncorrected p<0.01, voxel=100). Results: Following areas showed significant increase in rCBF after 3 weeks rTMS treatment: the cingulate gyrus, fusiform gyrus of right temporal lobe, precuneus, and left lateral globus pallidus. Significant decrement was noted in: the precental and middle frontal gyrus of right frontal lobe, and fusiform gyrus of left occipital lobe. Conclusion: Low-frequency rTMS on the right prefrontal cortex and high-frequency rTMS on the left prefrontal cortex for 3 weeks as an add-on regimen have increased and decreased rCBF in the specific brain regions in drug-resistant depressed patients. Further analyses correlating clinical characteristics and treatment paradigm with functional imaging data may be helpful in clarifying the pathophysiology of drug-resistant depressed patients.

Improvement of Seed Germination in a Spontaneous Autotetraploid of Poncirus and Chlorophyll Fluorescence of Seedlings in Salt Stress (동질 사배체 탱자의 종자 발아 증진과 염류 과잉에 따른 엽록소 형광 반응)

  • Chae, Chi Won;Yun, Su Hyun;Park, Jae Ho;Kim, Min Ju;Han, Seung Gab;Kang, Seok Beom;Koh, Sang Wook;Han, Sang Heon
    • Journal of Life Science
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    • v.23 no.9
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    • pp.1079-1087
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    • 2013
  • Speed germination success and robust vegetative growth of citrus rootstock through improved sowing methods and fertilizer inputs offer the usage of root system for the citrus. The current study evaluated the influence of seed coat removal and different fertilizer concentrations on plant germination and plant growth of spontaneous rootstock siblings. Decoated and coated seeds of diploid and tetraploid plants were sown in tubes. Commercial fertilizer concentrations of 0, 2, 4, 6, 8 and $10g{\cdot}l^{-1}$ were added. The experimental layout followed a randomized block $2{\times}6$ factorial design (seed coat removal ${\times}$ fertilizer concentration) for each rootstock. Fertilizer concentrations were 0, 10, 20 and $30g{\cdot}l^{-1}$ of the fertilizer for the resistance of the strength on the salt level. The germination rate of seeds without testa sown in vitro was improved (67-80%) compared to that of nontreated seeds. The eventual tree height of the seeds without testa in the diploid group was increased due to higher fertilization compared to that in the nontreated group. The removal of seed testa promoted the seed germination of both diploid and tetraploid trifoliate orange and resulted in greater height. Their vegetative development was also increased due to the increased fertilization of the rootstock. The Fv/Fm value for the diploid plants was 0.4 and 0.8 for the tetraploid ones under salt stress after 11 days of treatment. The removal of seed testa may improve the seed germination of trifoliate orange. Tetraploid trifoliate orange appears to possess resistance to salt stress compared to the diploid variety.

Effects of Pomace of Schizandra chinensis, Schizandrin, and Gomisin A on LPS-induced Inflammatory Responses in RAW264.7 Cells (오미자 박, schizandrin 및 gomisin A에 의한 RAW264.7 세포주에서 lipopolysaccharide로 유도된 염증 반응의 억제)

  • Seo, Yu-Mi;Kim, Hyun-Ji;Lee, Eun-Joo;Chung, Chungwook;Sung, Hwa-Jung;Sohn, Ho-Yong;Park, Jong-Yi;Kim, Jong-Sik
    • Journal of Life Science
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    • v.28 no.3
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    • pp.339-344
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    • 2018
  • Schizandra chinensis has been used as a traditional Chinese medicine and is known to have various bioactive components, including schizandrin and gomisin A. In the current study, we investigated the anti-inflammatory activities and their working mechanisms of ethanol extracts of pomace of Schizandra chinensis (PSC), schizandrin (SZ), and gomisin A (GA). First, we analyzed the effects of PSC on nitric oxide (NO) production and cell viabilities in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The results indicated that PSC dramatically reduced NO production in LPS-activated RAW264.7 cells in a dose-dependent manner without affecting cell viabilities. PSC also decreased the expression of pro-inflammatory genes iNOS and COX-2, whereas the expression of TNF-${\alpha}$ was not affected by PSC. In addition, PSC inhibited phosphorylation of p38, ERK1/2, and JNK but did not change the expression of their total protein. The results indicate that PSC can regulate LPS-induced inflammatory responses by suppressing MAPK (mitogen-activated protein kinase) signaling. We also analyzed the effects of SZ and GA on NO production and cell viabilities in RAW264.7 cells. The results showed that SZ and GA also decreased NO production in a dose-dependent manner in LPS-activated RAW 264.7 cells without affecting cell viabilities. SZ reduced the expression of iNOS, whereas GA downregulated iNOS and COX-2. Overall, these findings clarify the molecular mechanisms of the anti-inflammatory effects mediated by PSC, SZ, and GA.

Statistical Optimization of Production Medium for Enhanced Production of Itaconic Acid Biosynthesized by Fungal Cells of Aspergillus terreus (Aspergillus terreus에 의해 생합성되는 이타콘산의 생산성 증가를 위한 통계적 생산배지 최적화)

  • Jang, Yong-Man;Shin, Woo-Shik;Lee, Do-Hoon;Kim, Sang-Yong;Park, Chul-Hwan;Jeong, Yong-Seob;Chun, Gie-Taek
    • KSBB Journal
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    • v.24 no.1
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    • pp.30-40
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    • 2009
  • Statistical optimization of the production medium was carried out in order to find an optimal medium composition in itaconic acid fermentation process. Itaconic acid utilized in the manufacture of various synthetic resins is a dicarboxylic acid biosynthesized by fungal cells of Aspergillus terreus in a branch of the TCA cycle via decarboxylation of cis-aconitate. Through OFAT (one factor at a time) experiments, six components (glucose, fructose, sucrose, soluble starch, soybean meal and cottonseed flour) were found to have significant effects on itaconic production among various carbon- and nitrogen-sources. Hence, using these six factors, interactive effects were investigated via fractional factorial design, showing that the initial concentrations of sucrose and cottonseed flour should be high for enhanced production of itaconic acid. Furthermore, through full factorial design (FFD) experiments, negative effects of $KH_2PO_4$ and $MgSO_4$ on itaconic acid biosynthesis were demonstrated, when excess amounts of the each component were initially added. Based on the FFD analysis, further statistical experiments were conducted along the steepest ascent path, followed by response surface method (RSM) in order to obtain optimal concentrations of the constituent nutrients. As a result, optimized concentrations of sucrose and cottonseed flour were found to be 90.4g/L and 53.8g/L respectively, with the corresponding production level of itaconic acid to be 4.36 g/L (about 7 fold higher productivity as compared to the previous production medium). From these experimental results, it was assumed that optimum ratio of the constituent carbon (sucrose) and nitrogen (cottonseed flour) sources was one of the most important factors for the enhanced production of itaconic acid.

Hypoglycemic Effect of Chlorella sp. CMS-1 Hot Water Extract on Streptozotocin-Induced Diabetic Rats (Streptozotocin-유발 당뇨쥐에 대한 클로렐라 열수 추출물의 혈당 강하 효과)

  • Kim, Jung-Wook;Cha, Jae-Young;Heo, Jin-Sun;Jin, Hyun-Jin;Cho, Young-Su
    • Journal of Life Science
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    • v.18 no.11
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    • pp.1584-1591
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    • 2008
  • The effect of Chlorella hot water extract (CE) on hyperglycemia in streptozotocin- induced diabetic rats has not been studied. Therefore, hypoglycemic effect of CE in type I streptozotocin- induced diabetic rats was studied. Rats were fed a semisynthetic diet supplemented with either 3% (the STZ+CE3) and 6% (the STZ+CE6) CE or no supplement the Normal and the STZ-Control rats for 4 weeks. The concentrations of fasting and non-fasting blood glucose were higher in the STZ-Control rats than in the Normal rats, but this rise was lowered in the STZ+CE3 and the STZ+CE6 rats. Serum insulin concentrations were decreased with STZ injection, however, the decreased levels were almost restored to the Normal level with CE supplementation. The increased serum fructosamine levels associated with hyperglycemia were decreased with the CE treatment. The morphology of pancreatic islets in the Normal rat was round and maintained a typical arrangement. The STZ-Control pancreatic beta-cells were found to have significant swelling and severely morphological damaged, however, pancreatic tissue damage by STZ in the CE-supplemented diet group was ameliorated. This study shows that Chlorella hot water extract had a hypoglycemic effect on the STZ-diabetic rats via either increased insulin secretion during recovery or the prevention of STZ-induced pancreatic damage.

Extract from Prunus mume Sieb. et Zucc. Fruit Prevents LPS-induced Homotypic Aggregation of Monocytic THP-1 Cells via Suppression of Nitric Oxide Production and NF-κB Activation (매실 추출물의 산화질소 생성과 NF-κB 활성 조절을 통한 LPS유도성 THP-1 세포 동형성 응집의 억제 효과)

  • Lee, Hye-Rim;Park, Youngsook;Kim, Hyun Jeong;Lee, Aram;Choi, Jihea;Pyee, Jaeho;Park, Heonyong;Kim, Jongmin
    • Journal of Life Science
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    • v.25 no.7
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    • pp.801-809
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    • 2015
  • Homotypic cell adhesion (homotypic aggregation) in activated monocytes plays a central role in physiological and pathological processes including inflammatory responses, differentiation and migration. The extract of the Prunus mume Sieb. et Zucc. fruit (Maesil) has potential benefits to human health; such as anti-viral, anti-microbial, and anti-cancer activities. Indeed, Maesil extract may modulate inflammatory responses via interference with homotypic aggregation in monocytes. In the present study, the molecular mechanisms underpinning the therapeutic efficacy of Maesil extract in inflammatory diseases were investigated. It was found that Maesil extract inhibited homotypic aggregation in lipopolysaccharide (LPS)-activated monocytes. This was mediated by reduction of nitric oxide (NO) production, partly via inhibition of inducible nitric oxide synthase (iNOS) expression in LPS-activated THP-1 cells. It was confirmed that NO inhibition is a key mechanism in Maesil induced blockade of monocyte aggregation through identification of reversal of this inhibitory effect by the NO-producing agent S-nitroso-N-acetyl penicillamine (SNAP). In addition, Maesil extract significantly attenuated LPS-induced IκB-α phosphorylation and NF-κB translocation into the nucleus. In conclusion, Maesil extract exerts anti-inflammatory effects via inhibition of homotypic aggregation of LPS-activated monocytes through mechanisms involving the suppression of NO production and NF-κB activity, suggesting Maesil extract as a potential therapeutic candidate for the prevention and treatment of chronic inflammatory diseases.