• Title/Summary/Keyword: cause-effect pathway

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Effect of Byakangelicin from Angelica dahurica and its Semi-synthetic Derivatives on Aldose Reductase, Galactosemic Cataracts, the Polyol Contents and $Na^{+}$, $K^{+}$-ATPase activity in Sciatic Nerves of Streptozotocin-induced Diabetic Rats.

  • Lim, Soon-Sung;Jung, Sang-Hoon;Shin, Kuk-Hyun
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1998.11a
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    • pp.184-184
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    • 1998
  • Aldose reductase(AR), a rate-limiting enzyme in the polyol pathway, has been demonstrated to cause the intracellular accumulation of sorbitol or galactitol and hence to play key roles not only in the cataract formation in the lens but also in the pathogenesis of diabetic complications such as neuropathy, retinopathy and nephropathy, etc. In a series of investigations to evaluate potential AR inhibitors from medicinal plants, we have shown that some hot water extracts exhibited a significant inhibition of a significant inhibition of bovine lens AR in vitro. Among active plants, the roots of Angelica dahuria (Umbelliferae) were shown to have relatively potent AR inhibitory activity. Systematic fractionation of the ether soluble fraction monitored by bioassay led to isolation of two furanocoumarins, byakangelicin(I) and ter-O-methyl byakangelicin( II), were identified as potential AR inhibitors, their $IC_{50}$ values being 6.2 M and 2.8 M, respectively.

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Molecular Characterization of a Bombyx mori Protein Disulfide Isomerase(bPDI) (누에 배양세포로부터 분리한 Protein Disulfide Isomerase 유전자의 발현 특성)

  • 구태원;윤은영;황재삼;강석우;권오유
    • Journal of Life Science
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    • v.11 no.5
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    • pp.415-422
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    • 2001
  • Many secreted proteins have disulfide bonds that are important for their structure and function. Protein disulfide isomerase (PDI, EC 5.3.1.4.), an enzyme that catalyzes the formation and rearrangement of thiol/disulfide exchange reactions, is a resident of the endoplasmic reticulum (ER). The subcellular localization and its function as catalyst of disulfide bond formation in the biosynthesis of secretory and cell membrane proteins suggest that PDI plays a key role in the secretory pathway. We have isolated a cDNA encoding protein disulfide isomerase from Bombyx mori(bPDI). It has been characterized under ER stress conditions (dominantly induced by calcium ionophore A23187, tunicamycin and DTT), which is known to cause an accumulation of unfolded proteins in the ER. Furthermore, It has also been examined for tissue distribution(pronounced at the fat body), hormonal regulation (juvenile hormone, insulin and juvenile +transferrin; however, it is not effected by transferrin alone), and the effect of exogenous bacteria (peak at 16 h after infection) on the bPDI mRNA expression. The results suggest that bPDI is a member of the ER stress protein group, and it may play an important role in exogenous bacterial infection in fat body, and that homones regulate its expression.

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Factors on the Pathway from Trauma to Suicidal Ideation in Adolescents

  • Kwon, Seo Young;Nam, Ji Ae;Ko, Boo Sung;Lee, Chang Wha;Choi, Kyeong-Sook
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.30 no.1
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    • pp.26-33
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    • 2019
  • Objectives: Suicide is the most frequent cause of death among Korean adolescents, and adolescents who have experienced trauma have an increased risk of post-traumatic stress disorder (PTSD) symptoms, depression, and suicide attempts. However, resilience and self-esteem are protective factors. We examined the effects of resilience and self-esteem on the relationship among traumatic experiences, PTSD symptoms, depression, and suicidal ideation. Methods: Middle-school students (n=403) completed questionnaires assessing traumatic experiences, PTSD symptoms, depression, suicidal ideation, resilience, and self-esteem. Path analysis was performed to investigate the mediating effects of PTSD symptoms, resilience, self-esteem, and depression on the relationship between trauma exposure and suicidal ideation. Results: Traumatic experience was positively correlated with PTSD symptoms, depression, and suicidal ideation. PTSD symptoms and depression were positively correlated with suicidal ideation. The relationship between traumatic experiences and suicidal ideation was mediated by PTSD symptoms, which had both direct and indirect effects on suicidal ideation; the indirect effect was mediated by resilience, self-esteem, and depression. Conclusion: Korean adolescents who had experienced trauma were more likely to develop PTSD symptoms, increasing their risk of depression and suicidal ideation. However, self-esteem and resilience may help protect against depression and suicidal ideation. Our findings could inform suicide prevention initiatives.

Effects of Oxya chinensis sinuosa hot water extract on benign prostatic hyperplasia in LNCaP cells

  • Hyun Jung Lim;Sohyun Park;Ra-Yeong Choi;In-Woo Kim;Minchul Seo;Hae Yong Kweon;Joon Ha Lee
    • International Journal of Industrial Entomology and Biomaterials
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    • v.47 no.2
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    • pp.140-146
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    • 2023
  • In recent years, the number of patients with benign prostatic hyperplasia (BPH), a condition that commonly occurs in elderly men, has increased due to aging and the adoption of western dietary habits. Treatment with chemical drugs, such as finasteride or dutasteride, can cause side effects such as erectile dysfunction or sexual problems. This necessitates the development of remedies using natural substances derived from food ingredients. In this study, we investigated the inhibitory effects of Oxya chinensis sinuosa hot water extract (OCH) on BPH production in LNCaP cells, a hormone-dependent prostate cancer cell line. We found that the mRNA expression of androgen receptor (AR), prostate specific antigen (PSA), and, 5α-reductases 1, and 2 decreased following treatment with OCH. Furthermore, OCH treatment resulted in reduced protein expression of BPH regulators, such as AR. Collectively, these results suggest that OCH exerts a beneficial effect on BPH by inhibiting the AR signaling pathway, indicating the potential of OCH as a therapeutic agent for the prevention and treatment of BPH.

Effects of deoxynivalenol- and zearalenone-contaminated feed on the gene expression profiles in the kidneys of piglets

  • Reddy, Kondreddy Eswar;Lee, Woong;Jeong, Jin young;Lee, Yookyung;Lee, Hyun-Jeong;Kim, Min Seok;Kim, Dong-Woon;Yu, Dongjo;Cho, Ara;Oh, Young Kyoon;Lee, Sung Dae
    • Asian-Australasian Journal of Animal Sciences
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    • v.31 no.1
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    • pp.138-148
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    • 2018
  • Objective: Fusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEN), common contaminants in the feed of farm animals, cause immune function impairment and organ inflammation. Consequently, the main objective of this study was to elucidate DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the kidneys of piglets. Methods: Fifteen 6-week-old piglets were randomly assigned to three dietary treatments for 4 weeks: control diet, and diets contaminated with either 8 mg DON/kg feed or 0.8 mg ZEN/kg feed. Kidney samples were collected after treatment, and RNA-seq was used to investigate the effects on immune-related genes and gene networks. Results: A total of 186 differentially expressed genes (DEGs) were screened (120 upregulated and 66 downregulated). Gene ontology analysis revealed that the immune response, and cellular and metabolic processes were significantly controlled by these DEGs. The inflammatory stimulation might be an effect of the following enriched Kyoto encyclopedia of genes and genomes pathway analysis found related to immune and disease responses: cytokine-cytokine receptor interaction, chemokine signaling pathway, toll-like receptor signaling pathway, systemic lupus erythematosus (SLE), tuberculosis, Epstein-Barr virus infection, and chemical carcinogenesis. The effects of DON and ZEN on genome-wide expression were assessed, and it was found that the DEGs associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9, CXCL10, chemokine [C-C motif] ligand 4), proliferation (insulin like growth factor binding protein 4, IgG heavy chain, receptor-type tyrosine-protein phosphatase C, cytochrome P450 1A1, ATP-binding cassette sub-family 8), and other immune response networks (lysozyme, complement component 4 binding protein alpha, oligoadenylate synthetase 2, signaling lymphocytic activation molecule-9, ${\alpha}$-aminoadipic semialdehyde dehydrogenase, Ig lambda chain c region, pyruvate dehydrogenase kinase, isozyme 4, carboxylesterase 1), were suppressed by DON and ZEN. Conclusion: In summary, our results indicate that high concentrations of DON and ZEN suppress the inflammatory response in kidneys, leading to potential effects on immune homeostasis.

Effect of Fructose-1,6-diphosphate[FDP] on Red Blood Cells after Extracorporeal Circulation (체외순환후 fructose-1,6-diphosphatate[FDP]가 적혈구에 미치는 영향)

  • 이정렬
    • Journal of Chest Surgery
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    • v.25 no.7
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    • pp.693-701
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    • 1992
  • Extracorporeal cardiopulmonary bypass[CPB] has been associated with a wide variety of hematologic derangements, including a transient deformation and hemolysis of red blood cells[RBCs], which is supposed to be due to mechanical trauma and/or metabolic alterations. Since membrane integrity is, in part, maintained by energy requiring process, inadequate function of erythrocyte glycolytic pathway, which is inevitalble during CPB, may cause depletion of high energy phosphate pool and result in hemolysis. The authors performed an investigation to assess whether administration of Fructose-l, 6-diphsphate [FDP], which has been known to enhance intracellular glycolytic activities, could counteract erythrocyte hemolytic events caused by CPB. Sixty pateints with cyanotic congenital heart diseases, who underwent open heart surgery under CPB longer than 60 minutes, were randomly divided into two groups depending on whether use of FDP[Group FDP] or not[Group Control]. The age, sex, CPB time, preoperative hemoglobin level, disease entities were all similar[Table 1], and membrane type oxygenators were used in all patients. In Group, FDP, a dose of 250mg/kg body weight of FDP was administered by intravenous dripping every 12 hours from the morning of the operation to postoperative 48 hours, To demonstrate the degree and pattern of hemolysis of erythrocyte, reticulocyte count, indirect /direct bilirubin, haptoglobin, plasma hemoglobin, lactate dehydrogenase were measured every 12 hours from the time of cessation of CPB to 48 hours and RBC morphologic study, osmotic fragility test were done every 24 hours. All parameters revealed less hemolytic in group FDP [Fig. 1~5], though the differences between two groups were not significant, except plasma hemoglobin, lactate dehydrogenase changes. A pattern of sequential changes of plasma hemoglobin, lactate deh-ydrogenase showed the highest level at the time of CPB stop and abrupt decrease in following 24 hours in both groups, and statistically significant differences were demonstrated in group FDP at least for the first 12 hours postoperatively[p<0.05]. The authors conclude that they can expect the benificial effect of FDP on the maintenance of membrane stability of RBC probably by energy enhancement during the shock status of CPB, but FDP could not completely prevent the damaging effect on RBC by cardiopulmonary bypass

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Protective Effects of Nypa fruticans Wurmb against Oxidative DNA Damage and UVB-induced DNA Damage

  • So-Yeon Han;Tae-Won Jang;Da-Yoon Lee;Seo-Yoon Park;Woo-Jin Oh;Se Chul Hong;Jae-Ho Park
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2023.04a
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    • pp.54-54
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    • 2023
  • Nypa fruticans Wurmb (N. fruticans) is a plant that belongs to Araceae and N. fruticans is mainly found in tropical mangrove systems. The parts (leaves, stems, and roots) of N. fruticans are traditionally used for asthma, sore throat, and liver disease. N. fruticans contains flavonoids and polyphenols, which are substances that have inhibitory effects on cancer and oxidant. In previous studies, some pharmaceutical effects of N. fruticans on melanogenesis and inflammation have been reported. The present study is conducted to investigate the effect of the ethyl acetate fraction of N. fruticans (ENF) on oxidative DNA damage and UVB-induced DNA damage. DNA damage response (DDR) pathway is important in research on cancer, apoptosis, and so on. DDR pathways are considered a crucial factor affecting the alleviation of cellular damage. ENF could reduce oxidative DNA damage derived from reactive oxygen species by the Fenton reaction. Also, ENF reduced the intensity of intracellular ROS in the live cell image by DCFDA assay. UVB is known to cause skin and cellular damage, then finally contribute to causing the formation of tumors. As for the strategies of reducing DNA damage by UVB, inhibition of p53, H2AX, and Chk2 can be important indexes to protect the human body from DNA damage. As a result of confirming the protective effect of ENF for UVB damage, MMPs significantly decreased, and the expression of apoptosis-related factors tended to decrease. In conclusion, ENF can provide protective effects against double-stranded DNA break (DSB) caused by oxidative DNA damage and UVB-induced DNA damage. These results are considered to be closely related to the protective effect against radicals based on catechin, epicatechin, and isoquercitrin contained in ENF. Based on these results, it is thought that additional mechanism studies for inhibiting cell damage are needed.

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Whole-genome sequence association study identifies cyclin dependent kinase 8 as a key gene for the number of mummified piglets

  • Pingxian, Wu;Dejuan, Chen;Kai, Wang;Shujie, Wang;Yihui, Liu;Anan, Jiang;Weihang, Xiao;Yanzhi, Jiang;Li, Zhu;Xu, Xu;Xiaotian, Qiu;Xuewei, Li;Guoqing, Tang
    • Animal Bioscience
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    • v.36 no.1
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    • pp.29-42
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    • 2023
  • Objective: Pigs, an ideal biomedical model for human diseases, suffer from about 50% early embryonic and fetal death, a major cause of fertility loss worldwide. However, identifying the causal variant remains a huge challenge. This study aimed to detect single nucleotide polymorphisms (SNPs) and candidate genes for the number of mummified (NM) piglets using the imputed whole-genome sequence (WGS) and validate the potential candidate genes. Methods: The imputed WGS was introduced from genotyping-by-sequencing (GBS) using a multi-breed reference population. We performed genome-wide association studies (GWAS) for NM piglets at birth from a Landrace pig populatiGWAS peak located on SSC11: 0.10 to 7.11 Mbp (Top SNP, SSC11:1,889,658 bp; p = 9.98E-13) was identified in cyclin dependent kinase on. A total of 300 Landrace pigs were genotyped by GBS. The whole-genome variants were imputed, and 4,252,858 SNPs were obtained. Various molecular experiments were conducted to determine how the genes affected NM in pigs. Results: A strong GWAS peak located on SSC11: 0.10 to 7.11 Mbp (Top SNP, SSC11:1,889,658 bp; p = 9.98E-13) was identified in cyclin dependent kinase 8 (CDK8) gene, which plays a crucial role in embryonic retardation and lethality. Based on the molecular experiments, we found that Y-box binding protein 1 (YBX1) was a crucial transcription factor for CDK8, which mediated the effect of CDK8 in the proliferation of porcine ovarian granulosa cells via transforming growth factor beta/small mother against decapentaplegic signaling pathway, and, as a consequence, affected embryo quality, indicating that this pathway may be contributing to mummified fetal in pigs. Conclusion: A powerful imputation-based association study was performed to identify genes associated with NM in pigs. CDK8 was suggested as a functional gene for the proliferation of porcine ovarian granulosa cells, but further studies are required to determine causative mutations and the effect of loci on NM in pigs.

Molecular Mechanisms of Protein Kinase C-induced Apoptosis in Prostate Cancer Cells

  • Gonzalez-Guerrico, Anatilde M.;Meshki, John;Xiao, Liqing;Benavides, Fernando;Conti, Claudio J.;Kazanietz, Marcelo G.
    • BMB Reports
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    • v.38 no.6
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    • pp.639-645
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    • 2005
  • Protein kinase C (PKC) isozymes, a family of serine-threonine kinases, are important regulators of cell proliferation and malignant transformation. Phorbol esters, the prototype PKC activators, cause PKC translocation to the plasma membrane in prostate cancer cells, and trigger an apoptotic response. Studies in recent years have determined that each member of the PKC family exerts different effects on apoptotic or survival pathways. $PKC{\delta}$, one of the novel PKCs, is a key player of the apoptotic response via the activation of the p38 MAPK pathway. Studies using RNAi revealed that depletion of $PKC{\delta}$ totally abolishes the apoptotic effect of the phorbol ester PMA. Activation of the classical $PKC{\alpha}$ promotes the dephosphorylation and inactivation of the survival kinase Akt. Studies have assigned a pro-survival role to $PKC{\varepsilon}$, but the function of this PKC isozyme remains controversial. Recently, it has been determined that the PKC apoptotic effect in androgen-dependent prostate cancer cells is mediated by the autocrine secretion of death factors. $PKC{\delta}$ stimulates the release of $TNF{\alpha}$ from the plasma membrane, and blockade of $TNF{\alpha}$ secretion or $TNF{\alpha}$ receptors abrogates the apoptotic response of PMA. Molecular analysis indicates the requirement of the extrinsic apoptotic cascade via the activation of death receptors and caspase-8. Dissecting the pathways downstream of PKC isozymes represents a major challenge to understanding the molecular basis of phorbol ester-induced apoptosis.

Effect of Anemarrhenae Rhizoma Ethanol Extract on Apoptosis Induction of HT-29 Human Colon Cancer Cells (지모(知母)에탄올추출물의 HT-29대장암세포 Apoptosis 유도효과)

  • Kim, Tae-Hyun;Kim, Pom-Ho;Jeon, Byoung-Kook;Yoon, Jeong-Rock;Woo, Won-Hong;Mun, Yeun-Ja;Lee, Jang-Cheon;Lee, Boo-Kyun;Park, oung-Gue;Lim, Kyu-Sang
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.24 no.1
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    • pp.16-24
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    • 2011
  • Objective : In this study, we investigated the effects of ethanol extract of Anemarrhenae Rhizoma (EAR) on the proliferation and apoptosis induction of HT-29 human colon cancer cells. Methods : Cell viability of HT-29 cells were measured by MTT assay and apoptisis-related proteins were assessed using western blotting. Chromatin condensation of HT-29 cells stained with Hoechst 33258. Results : In the present study, we demonstrated that EAR exhibited significant cytotoxicity in HT-29 cells. The induction of apoptosis in HT-29 cells by EAR treatment was characterized by chromatin condensation and the activation of caspase-3. EAR-induced apoptosis is accompanied by the release of cytochrome c and the specific proteolytic cleavage of PARP. EAR was appeared cytotoxic effect to HT-29 cells in a dose-dependent manner. Concomitantly, EAR treatment led to increase in the caspase-9. The reduction of Bcl-2 and truncation of Bid were induced by EAR. Conclusion : We studied that the EAR induced apoptosis in human colon adenocarcinoma HT-29 cells. These results indicated that EAR can cause apoptosis through mitochondria/caspase pathway in human HT-29 cells.