• Journal of Ginseng Research
• /
• 제40권2호
• /
• pp.185-195
• /
• 2016

Background: To investigate the effect of pectinase-treated Panax ginseng (GINST) in cellular and male subfertility animal models. Methods: Hydrogen peroxide ($H_2O_2$)-induced mouse spermatocyte GC-2spd cells were used as an in vitro model. Cell viability was measured using MTT assay. For the in vivo study, GINST (200 mg/kg) mixed with a regular pellet diet was administered orally for 4 mo, and the changes in the mRNA and protein expression level of antioxidative and spermatogenic genes in young and aged control rats were compared using real-time reverse transcription polymerase chain reaction and western blotting. Results: GINST treatment ($50{\mu}g/mL$, $100{\mu}g/mL$, and $200{\mu}g/mL$) significantly (p < 0.05) inhibited the $H_2O_2$-induced ($200{\mu}M$) cytotoxicity in GC-2spd cells. Furthermore, GINST ($50{\mu}g/mL$ and $100{\mu}g/mL$) significantly (p < 0.05) ameliorated the $H_2O_2$-induced decrease in the expression level of antioxidant enzymes (peroxiredoxin 3 and 4, glutathione S-transferase m5, and glutathione peroxidase 4), spermatogenesis-related protein such as inhibin-${\alpha}$, and specific sex hormone receptors (androgen receptor, luteinizing hormone receptor, and follicle-stimulating hormone receptor) in GC-2spd cells. Similarly, the altered expression level of the above mentioned genes and of spermatogenesis-related nectin-2 and cAMP response element-binding protein in aged rat testes was ameliorated with GINST (200 mg/kg) treatment. Taken together, GINST attenuated $H_2O_2$-induced oxidative stress in GC-2 cells and modulated the expression of antioxidant-related genes and of spermatogenic-related proteins and sex hormone receptors in aged rats. Conclusion: GINST may be a potential natural agent for the protection against or treatment of oxidative stress-induced male subfertility and aging-induced male subfertility.

• Journal of Ginseng Research
• /
• 제42권1호
• /
• pp.107-115
• /
• 2018

Background: Depression is one of the most commonly diagnosed neuropsychiatric diseases, but the underlying mechanism and medicine are not well-known. Although Panax ginseng has been reported to exert protective effects in various neurological studies, little information is available regarding its antidepressant effects. Methods: Here, we examined the antidepressant effect and underlying mechanism of P. ginseng extract (PGE) in a chronic restraint stress (CRS)-induced depression model in mice. Results: Oral administration of PGE for 14 d decreased immobility (depression-like behaviors) time in forced swim and tail suspended tests after CRS induction, which corresponded with attenuation of the levels of serum adrenocorticotropic hormone and corticosterone, as well as attenuated c-Fos expression in the amygdala. PGE enhanced messenger RNA expression level of brain-derived neurotrophic factor but ameliorated microglial activation and neuroinflammation (the level of messenger RNA and protein expression of cyclooxygenase-2 and inducible nitric oxide synthase) in the amygdala of mice after CRS induction. Interestingly, 14-d treatment with celecoxib, a selective cyclooxygenase-2 inhibitor, and $N_{\omega}$-nitro-L-arginine methyl ester hydrochloride, a selective inducible nitric oxide synthase inhibitor, attenuated depression-like behaviors after CRS induction. Additionally, PGE inhibited the upregulation of the nuclear factor erythroid 2 related factor 2 and heme oxygenase-1 pathways. Conclusion: Taken together, our findings suggest that PGE exerts antidepressant-like effect of CRS-induced depression by antineuroinflammatory and antioxidant (nuclear factor erythroid 2 related factor 2/heme oxygenase-1 activation) activities by inhibiting the hypothalamo-pituitary-adrenal axis mechanism. Further studies are needed to evaluate the potential of components of P. ginseng as an alternative treatment of depression, including clinical trial evaluation.

• Toxicological Research
• /
• 제22권1호
• /
• pp.23-30
• /
• 2006

Among poly aromatic hydrocarbons, dioxin and PCBs are the most controversial environmental pollutants in our modern life. These pollutants are known as human carcinogens, and liver is the most sensitive target in animal cancer models. Specific aims of the study were focused on the mechanism of carcinogenesis in hepatocytes and the structure-activity relation among these diverse environmental chemicals. Because key mechanisms of dioxin-induced carcinogenesis in human epithelial cell model are the alteration of signal transduction pathway and PKC isoforms, the alteration of the signal transduction pathways and other factors associated with carcinogenesis were studied. Rat hepatocytes cultured under the sandwich protocols were exposed with the various concentration of dioxins and PCBs, and signal transduction pathway, protein kinase C isoforms, oxidant stress, and apoptotic nuclei were evaluated. Since it is important to understand the structure-activity relation among these chemicals to properly assess the carcinogenic potentials, the study analyzed the parameters associated with carcinogenic processes, based on their structural characteristics. In addition, signal transduction pathways and PKC isoforms involved in inhibition of UV-induced apoptosis were also analyzed to elaborate the tumor promotion mechanism of these chemicals. Induction of apoptosis by UV irradiation was optimal at $60\;J/m^2$ in primary hepatocyte in culture. Compared to non coplanar PCBs such as PCB 114 and PCB 153, coplanar PCBs such as PCB 77 and PCB126 showed a stronger inhibition of apoptosis induced by UV irradiation. Production of reactive oxygen species (ROS) was more stimulated by non-coplanar PCBs than coplanar PCBs with the most potent induction of ROS by chlorinated non-coplanar PCB. As compared to the level of induction by PCB126, non-coplanar PCB153 showed a higher increase of intracellular concentrations. Besides the alteration of intracellular calcium concentration, translocation of PKC from cytosolic fraction to membrane fraction was clearly observed upon the exposure of non-coplanar PCB. Taken together, the present study demonstrated that there is a potent structure-activity relationship among PCB congeners and the mechanism of PAH-induced carcinogenesis is structure-specific. The study suggested that more diverse pathways of PAH-induced carcinogenesis should be taken into account beyond the boundary of Ah receptor dogma to assess the health impact of PAH with more accuracy.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권7호
• /
• pp.3213-3222
• /
• 2016

Background: Methyl donor status influences DNA stability and DNA methylation although little is known about effects on DNA methyltransferases. The aim of this study was to determine whether methyl-donor status influences DNA methyltransferase (Dnmt) gene expression in cervical cancer cells, and if so, whether there are associated effects on global DNA methylation. Materials and Methods: The human cervical cancer cell line, C4-II, was grown in complete medium and medium depleted of folate (F-M+) and folate and methionine (F-M-). Growth rate, intracellular folate, intracellular methionine and homocysteine in the extracellular medium were measured to validate the cancer cell model of methyl donor depletion. Dnmt expression was measured by qRT-PCR using relative quantification and global DNA methylation was measured using a flow cytometric method. Results: Intracellular folate and methionine concentrations were significantly reduced after growth in depleted media. Growth rate was also reduced in response to methyl donor depletion. Extracellular homocysteine was raised compared with controls, indicating disturbance to the methyl cycle. Combined folate and methionine depletion led to a significant down-regulation of Dnmt3a and Dnmt3b; this was associated with an 18% reduction in global DNA methylation compared with controls. Effects of folate and methionine depletion on Dnmt3a and 3b expression were reversed by transferring depleted cells to complete medium. Conclusions: Methyl donor status can evidently influence expression of Dnmts in cervical cancer cells, which is associated with DNA global hypomethylation. Effects on Dnmt expression are reversible, suggesting reversible modulating effects of dietary methyl donor intake on gene expression, which may be relevant for cancer progression.

• Journal of Nutrition and Health
• /
• 제46권4호
• /
• pp.307-314
• /
• 2013

본 연구에서는 레스베라트롤이 당뇨병 및 비알코올성 지방간 질환 개선 효과를 가지는지를 규명하기 위해 고지방 식이 유도 비만 쥐를 대상으로 레스베라트롤을 4주간 osmotic pump를 사용하여 공급한 후 정상대조군과 고지방식이 제공 비만군과 비교 분석하였고 그 결과는 다음과 같다. 1) 고지방식이 유도 비만 쥐를 대상으로 8 mg/kg/day의 레스베라트롤을 4주간 처리한 결과 체중 변화, 간 조직 중량, 식이 섭취량에 영향을 미치지 않았다. 2) 레스베라트롤은 공복 혈당, 혈청 내 인슐린, 중성지방, 총 콜레스테롤 농도를 낮추었고, 인슐린 작용을 촉진시키는 혈청 아디포넥틴 수준을 개선시켰다. 또한, 고지방식이에 의해 높아진 간 조직 내 중성지방과 총콜레스테롤 농도를 낮추어 레스베라트롤이 지방간 개선 효과를 가질 수 있음을 제안하였다. 3) 자가포식의 표지인자인 autophagosome 생성과 LC3-II 형성 분석 결과, 고지방식이에 의해 과도한 자가포식이 유도되었음을 확인하였다. 레스베라트롤 처리는 이중막을 가지는 autophagosome 생성과 LC3-II 형성을 감소시켜 고지방식이에 의해 유도된 과도한 자가포식을 억제시킴을 보여주었다. 결론적으로 고지방식이와 함께 레스베라트롤을 제공하는 것은 당뇨병과 비알코올성 지방간 질환 관련 대사 인자들을 개선시키고, 이는 간에서의 자가포식 조절과 관련이 있다고 제안한다.

• Asian-Australasian Journal of Animal Sciences
• /
• 제22권7호
• /
• pp.943-954
• /
• 2009

Diacylglycerol acyltransferase (DGAT) is a key enzyme that catalyzes the final and rate-limiting step of triglyceride synthesis. Both DGAT1 and DGAT2 genes code proteins with DGAT activity. Studies have shown DGAT1 polymorphisms associate with intramuscular fat deposition in beef cattle, but fewer associations between DGAT2 and beef cattle economic traits have been reported. The objective of this study was to investigate single nucleotide polymorphism (SNP) in intron3 of bovine DGAT2 and evaluate the associations of that with carcass, meat quality, and fat yield traits. Test animals were 157 commercial feedlot steers belonging to 3 Chinese native breeds (22 for Luxi, 24 for Jinnan, and 23 for Qinchuan), 3 cross populations (20 for Charolais${\times}$Fuzhou, 18 for Limousin ${\times}$Luxi, and 17 for Simmental${\times}$Jinan) and 1 Taurus pure breed population (16 Angus steers). In the current study, 15 SNP were discovered in intron3 and exon4 of DGAT2 at positions 65, 128, 178, 210, 241, 255, 270, 312, 328, 334, 365, 366, 371, 415, and 437 (named as their positions in PCR amplified fragments). Only 7 of them (128, 178, 241, 270, 312, 328, and 371) were analyzed, because SNP in three groups (65-128-255, 178-210-365 and 241-334-366) were in complete linkage disequilibrium within the group, and SNP 415 was a deletion and 437 was a null mutation. Frequencies for rare alleles in the 3 native breed populations were higher than in the 3 cross populations for 178 (p = 0.04), 270 (p = 0.001), 312 (p = 0.03) and 371 (p = 0.002). A general linear model was used to evaluate the associations between either SNP genotypes or allele substitutions and the measured traits. Results showed that SNP 270 had a significant association with the fat yield associated with kidney, pelvic cavity, heart, intestine, and stomach (KPHISY). Animals with genotype CC and CT for 270 had less (CC: -7.71${\pm}$3.3 kg and CT: -5.34${\pm}$2.5 kg) KPHISY than animals with genotype TT (p = 0.02). Allele C for 270 was associated with an increase of -4.26${\pm}$1.52 kg KPHISY (p = 0.006) and $-0.92{\pm}0.45%$ of retail cuts weight percentage (NMP, Retail cuts weight/slaughter body weight) (p = 0.045); allele G for 312 was associated with an increase of -5.45${\pm}$2.41 kg KPHISY (p = 0.026). An initial conclusion was that associations do exist between DGAT2 gene and carcass fat traits. Because of the small sample size of this study, it is proposed that further effort is required to validate these findings in larger populations.

• Journal of Microbiology and Biotechnology
• /
• 제27권11호
• /
• pp.2044-2051
• /
• 2017

The main pathological hallmark of Alzheimer's disease is the deposition of amyloid-beta ($A{\beta}$) peptides in the brain. $A{\beta}$ has been widely used to mimic several aspects of Alzheimer's disease. However, several characteristics of amyloid-induced Alzheimer's disease pathology are not well established, especially in mice. The present study aimed to develop a new Alzheimer's disease model by investigating how $A{\beta}$ can be effectively aggregated using prokaryotes and eukaryotes. To express the $A{\beta}42$ complex in HEK293 cells, we cloned the $A{\beta}42$ region in a tandem repeat and incorporated the resulting construct into a eukaryotic expression vector. Following transfection into HEK293 cells via lipofection, cell viability assay and western blotting analysis revealed that exogenous $A{\beta}42$ can induce cell death and apoptosis. In addition, recombinant His-tagged $A{\beta}42$ was successfully expressed in Escherichia coli BL21 (DE3) and not only readily formed $A{\beta}$ complexes, but also inhibited the proliferation of SH-SY5Y cells and E. coli. For in vivo testing, recombinant His-tagged $A{\beta}42$ solution ($3{\mu}g/{\mu}l$ in $1{\times}PBS$ containing $1mM\;Ni^{2+}$) was injected stereotaxically into the left and right lateral ventricles of the brains of C57BL/6J mice (n = 8). Control mice were injected with $1{\times}PBS$ containing $1mM\;Ni^{2+}$ following the same procedure. Ten days after the sample injection, the Morris water maze test confirmed that exogenous $A{\beta}$ caused an increase in memory loss. These findings demonstrated that $Ni^{2+}$ is capable of complexing the 50-kDa amyloid and that intracerebroventricular injection of $A{\beta}42$ can lead to cognitive impairment, thereby providing improved Alzheimer's disease models.

• Toxicological Research
• /
• 제34권3호
• /
• pp.221-229
• /
• 2018

Tenofovir nanoparticles are novel therapeutic intervention in human immunodeficiency virus (HIV) infection reaching the virus in their sanctuary sites. However, there has been no systemic toxicity testing of this formulation despite global concerns on the safety of nano drugs. Therefore, this study was designed to investigate the toxicity of Tenofovir nanoparticle (NTDF) on the liver and kidney using an animal model. Fifteen adult male Sprague-Dawley (SD) rats maintained at the animal house of the biomedical resources unit of the University of KwaZulu-Natal were weighed and divided into three groups. Control animals (A) were administered with normal saline (NS). The therapeutic doses of Tenofovir (TDF) and nanoparticles of Tenofovir (NTDF) were administered to group B and C and observed for signs of stress for four weeks after which animals were weighed and sacrificed. Liver and kidney were removed and fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT) and liver function test (LFT). Cellular measurements and capturing were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, p values < 0.05 were significant. We observed no signs of behavioural toxicity and no mortality during this study, however, in the kidneys, we reported mild morphological perturbations widening of Bowman's space, and vacuolations in glomerulus and tubules of TDF and NTDF animals. Also, there was a significant elevation of glycogen deposition in NTDF and TDF animals when compared with control. In the liver, there were mild histological changes with widening of sinusoidal spaces, vacuolations in hepatocytes and elevation of glycogen deposition in TDF and NTDF administered animals. In addition to this, there were no significant differences in stereological measurements and cell count, LFT, RFT, weight changes and organo-somatic index between treatment groups and control. In conclusion, NTDF and TDF in therapeutic doses can lead to mild hepatic and renal histological damage. Further studies are needed to understand the precise genetic mechanism.

• 대한조선학회논문집
• /
• 제28권1호
• /
• pp.12-18
• /
• 1991

3차원(次元) 탱크내에서의 유체(流體)의 슬로싱 현상(現象)에 관하여 경계적분법(境界積分法)의 패널 방법(方法)을 이용한 경계치(境界値) 문제해법(問題解法)으로 수치계산(數値計算)하였다. Shinkai는 경계요소(境界要素)의 소오스의 세기가 절점(節点) 사이에서 선형변화(線型變化)하도록 계산하였음에 반하여 본 연구에서는 삼각형(三角形)패널마다 일정(一定)한 세기의 소오스를 분포(分布)시켰다. 각(各) 시간(時間)단계에서의 소오스의 세기는 Green 정리(定理)에 의한 제2종(第2種) Fredbolm적분(積分) 방정식(方程式)을 풀어서 구하며, 시간(時間)이 경과함에 따른 수치 계산과 이에 따른 오차(誤差)의 누적을 피하기 위하여 Adam-Bashforth-Moulton 방법(方法)을 이용하였다. 강제조화(强制調和)동요하는 선박의 구형(球形)탱크가 부분적재(部分積載)된 경우에 대하여 수치(數値)계산한 결과, 자유표면(自由表面)의 높이 계산치(計算値)는 Shinkai의 결과와 비교한 바 비교적 적은 시간동안에는 잘 일치하고 있음을 확인하였다. 본 수치 계산방법(方法)의 정도(精度)를 검토하기 위하여 입력(入力) 및 출력(出力) 에너지가 보존(保存)되는지를 확인하여 보았는데, 시간이 경과되면서 약간의 오차가 있지만 문제의 비선형성(非線型性), 모델의 패널수가 작음을 감안할때는 인정할 만한 정확도(正確度)로 판단된다.

• 한국음향학회지
• /
• 제31권6호
• /
• pp.373-383
• /
• 2012

수중음향통신 시스템의 성능은 다중경로 전달특성에 의해 발생하는 인접심볼간 간섭(ISI, Inter-Symbol Interference)과 도플러 편이(Doppler shift)에 영향을 받는다. 그러므로 해양도파관 환경의 수치실험은 다중경로에 의해 발생하는 시간 확산과 송 수신기의 움직임으로 발생하는 도플러 편이로 인한 시변동성을 고려해야 한다. 본 논문에서는 해양도파관 환경의 변동성을 고려한 가상의 신호 생성 시뮬레이터인 VirTEX(Virtual Time series EX-periment)를 활용[10]하여 시뮬레이터 기반 수중음향통신 시스템의 성능을 검증하였다. 수중음향통신 시스템 성능 검증을 위해 해상실험에서 획득한 실측데이터와 VirTEX 기반 수치모의 된 데이터의 채널응답분석 및 통신성능 분석을 수행한다. 해상실험 및 수치모의실험을 통해 수신된 탐침신호의 채널 임펄스 응답(channel impulse response) 분석결과 다중경로 개수와 깊이에 따른 채널응답의 변화 경향이 매우 유사함을 확인하였으며, 해상실험 및 수치모의실험을 통해 수신된 통신신호의 BER(Bit Error Rate)을 통하여 VirTEX 시뮬레이터를 활용한 수중음향통신 시스템의 통신성능을 확인하였다.