Synergistic Effects of Leflunomide and Benazepril in Streptozotocin-Induced Diabetic Nephropathy

Jin, Hua,Piao, Shang Guo,Jin, Ji Zhe,Jin, Ying Shun,Cui, Zhen Hua,Jin, Hai Feng,Zheng, Hai Lan,Li, Jin Ji,Jiang, Yu Ji,Yang, Chul Woo,Li, Can S.Karger 2014 The Nephron Journals Vol.126 No.3

<P>Abstract</P><P><B><I>Background:</I></B> Leflunomide (LEF) and benazepril have renoprotective effects on diabetic nephropathy (DN) through their anti-inflammatory and anti-fibrotic activities. This study investigated whether combined treatment using LEF and benazepril affords superior protection compared with the respective monotherapies. <B><I>Methods:</I></B> Diabetes was induced with streptozotocin (STZ, 65 mg/kg) by intraperitoneal injection in male Wistar rats. Two weeks after STZ injection, diabetic rats were treated daily for 12 weeks with LEF (10 mg/kg), benazepril (10 mg/kg), or a combination of both. Basic parameters (body weight, fasting blood glucose level, and 24 h urinary protein excretion), histopathology, inflammatory [inflammatory cell infiltration (ED-1), monocyte chemoattractant protein-1 (MCP-1), and Toll-like receptor-2 (TLR-2)] and glomerulosclerotic factors [transforming growth factor-β<SUB>1</SUB> (TGF-β<SUB>1</SUB>) and connective tissue growth factor (CTGF)], and oxidative stress (8-hydroxy-2'-deoxyguanosine, 8-OHdG) were studied. <B><I>Results:</I></B> Benazepril or LEF treatment significantly prevented body weight loss and 24 h urinary protein excretion induced by diabetes; combined treatment with LEF and benazepril further improved these parameters compared with giving each drug alone (all p < 0.01). Increased expression of inflammatory (MCP-1 and TLR-2) and glomerulosclerotic (TGF-β<SUB>1</SUB> and CTGF) factors in diabetic rat kidney was reduced by treatment with either LEF or benazepril and was further reduced by the combined administration of the two drugs (p < 0.01). These effects were accompanied by suppression of urinary 8-OHdG excretion. There was no significant between-group difference in blood glucose level. <B><I>Conclusions:</I></B> LEF treatment lessens DN, and combined treatment with LEF and benazepril provides synergistic effects in preventing DN.</P><P>© 2014 S. Karger AG, Basel</P>

Glutathione-S-transferase (GSTM1, GSTT1) Null Phenotypes and Risk of Lung Cancer in a Korean Population

Piao, Jin-Mei,Shin, Min-Ho,Kim, Hee Nam,Cui, Lian-Hua,Song, Hye-Rim,Kweon, Sun-Seog,Choi, Jin-Su,Kim, Young-Chul,Oh, In-Jae,Kim, Kyu-Sik Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

Purpose: The aim of this study was to evaluate any association of GSTM1 and GSTT1 null genotypes with the risk of lung cancer in a South Korean population. Methods: We conducted a large-scale, population-based case-control study including 3,933 lung cancer cases and 1,699 controls. Genotypes of GSTM1 and GSTT1 were determined using real-time polymerase chain reaction. Results: In logistic regression analysis adjusted for age and smoking, we did not find any association between GSTM1 or GSTT1 and LC risk in women. However, in men, the GSTM1 and GSTTI null genotypes were borderline associated with risk (OR=1.18, 95% CI=0.99-1.41 for GSTM1, OR=1.18, 95% CI=0.99-1.41 for GSTT1), and combined GSTM1 and GSTT1 null genotypes conferred an increased risk for LC in men (OR=1.39, 95% CI=1.08-1.78). The OR for the GSTT1 null genotype was greater in subjects aged 55 years old or younger (OR=1.45, 95% CI=1.09-1.92 for men; OR=1.36, 95% CI=0.97-1.90 for women), than in those over age 55 (OR=1.03, 95% CI=0.83-1.27 for men; OR=0.86, 95% CI=0.66-1.12 for women) in both genders (p for interaction <0.05). Conclusions: In the Korean population, the GSTM1 and GSTT1 null genotypes are risk factors for LC in men; the GSTT1 null genotype has a more prominent effect on LC risk in younger people (age 55 years and under) than in older individuals.

Ginsenoside Rh2 attenuates microglial activation against toxoplasmic encephalitis via TLR4/NF-kB signaling pathway

Xiang Xu,Lan Jin,Tong Jiang,Ying Lu,Fumie Aosai,Hu-Nan Piao,Guang-Hua Xu,Cheng-Hua Jin,Xue-Jun Jin,Juan Ma,Lian-Xun Piao 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.5

Background: Ginsenoside Rh2 (GRh2) is a characterized component in red ginseng widely used in Korea and China. GRh2 exhibits a wide range of pharmacological activities, such as anti-inflammatory, antioxidant, and anticancer properties. However, its effects on Toxoplasma gondii (T. gondii) infection have not been clarified yet. Methods: The effect of GRh2 against T. gondii was assessed under in vitro and in vivo experiments. The BV2 cells were infected with tachyzoites of T. gondii RH strain, and the effects of GRh2 were evaluated by MTT assay, morphological observations, immunofluorescence staining, a trypan blue exclusion assay, reverse transcription PCR, and Western blot analyses. The in vivo experiment was conducted with BALB/c mice inoculated with lethal amounts of tachyzoites with or without GRh2 treatment. Results and conclusion: The GRh2 treatment significantly inhibited the proliferation of T. gondii under in vitro and in vivo studies. Furthermore, GRh2 blocked the activation of microglia and specifically decreased the release of inflammatory mediators in response to T. gondii infection through TLR4/NF-kB signaling pathway. In mice, GRh2 conferred modest protection from a lethal dose of T. gondii. After the treatment, the proliferation of tachyzoites in the peritoneal cavity of infected mice markedly decreased. Moreover, GRh2 also significantly decreased the T. gondii burden in mouse brain tissues. These findings indicate that GRh2 exhibits an antieT. gondii effect and inhibits the microglial activation through TLR4/NF-kB signaling pathway, providing the basic pharmacological basis for the development of new drugs to treat toxoplasmic encephalitis.

Ginsenoside Rh2 reduces depression in offspring of mice with maternal toxoplasma infection during pregnancy by inhibiting microglial activation via the HMGB1/TLR4/NF-kB signaling pathway

Xiang Xu,Yu-Nan Lu,Jia-Hui Cheng,Hui-Wen Lan,Jing-Mei Lu,Guang-Nan Jin,Guang-Hua Xu,Cheng-Hua Jin,Juan Ma,Hu-Nan Piao,Xuejun Jin,Lian-Xun Piao 고려인삼학회 2022 Journal of Ginseng Research Vol.46 No.1

Background: Maternal Toxoplasma gondii (T. gondii) infection during pregnancy has been associated with various mental illnesses in the offspring. Ginsenoside Rh2 (GRh2) is a major bioactive compound obtained from ginseng that has an anti-T. gondii effect and attenuates microglial activation through toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-kB) signaling pathway. GRh2 also alleviated tumor-associated or lipopolysaccharide-induced depression. However, the effects and potential mechanisms of GRh2 on depression-like behavior in mouse offspring caused by maternal T. gondii infection during pregnancy have not been investigated. Methods: We examined GRh2 effects on the depression-like behavior in mouse offspring, caused by maternal T. gondii infection during pregnancy, by measuring depression-like behaviors and assaying parameters at the neuronal and molecular level. Results: We showed that GRh2 significantly improved behavioral measures: sucrose consumption, forced swim time and tail suspended immobility time of their offspring. These corresponded with increased tissue concentrations of 5-hydroxytryptamine and dopamine, and attenuated indoleamine 2,3-dioxygenase or enhanced tyrosine hydroxylase expression in the prefrontal cortex. GRh2 ameliorated neuronal damage in the prefrontal cortex. Molecular docking results revealed that GRh2 binds strongly to both TLR4 and high mobility group box 1 (HMGB1). Conclusion: This study demonstrated that GRh2 ameliorated the depression-like behavior in mouse offspring of maternal T. gondii infection during pregnancy by attenuating the excessive activation of microglia and neuroinflammation through the HMGB1/TLR4/NF-kB signaling pathway. It suggests that GRh2 could be considered a potential therapy in preventing and treating psychiatric disorders in the offspring mice of mothers with prenatal exposure to T. gondii infection.

High Performance Current Sensing Circuit for Current-Mode DC-DC Buck Converter

Jin, Hai-Feng,Piao, Hua-Lan,Cui, Zhi-Yuan,Kim, Nam-Soo The Korean Institute of Electrical and Electronic 2010 Transactions on Electrical and Electronic Material Vol.11 No.1

A simulation study of a current-mode direct current (DC)-DC buck converter is presented in this paper. The converter, with a fully integrated power module, is implemented by using sense method metal-oxide-semiconductor field-effect transistor (MOSFET) and bipolar complementary metal-oxide-semiconductor (BiCMOS) technology. When the MOSFET is used in a current sensor, the sensed inductor current with an internal ramp signal can be used for feedback control. In addition, the BiCMOS technology is applied in the converter for an accurate current sensing and a low power consumption. The DC-DC converter is designed using the standard $0.35\;{\mu}m$ CMOS process. An off-chip LC filter is designed with an inductance of 1 mH and a capacitance of 12.5 nF. The simulation results show that the error between the sensing signal and the inductor current can be controlled to be within 3%. The characteristics of the error amplification and output ripple are much improved, as compared to converters using conventional CMOS circuits.

The Bacterial Surface Expression of SARS Viral Epitope using Salmonella typhi Cytolysin A

Piao, Hong-Hua,Seong, Ji-Hyoun,Song, Man-Ki,Kim, Youn-Uck,Shin, Dong-Jun,Choy, Hyon-E,Hong, Yeong-Jin The Korean Society for Microbiology 2009 Journal of Bacteriology and Virology Vol.39 No.2

The cytolysin A (ClyA) is a 34 kDa pore-forming cytotoxic protein and expressed by some enteric bacteria including Salmonella typhi. This toxin is transported on the bacterial surface and secreted without posttranslational modification. Using the surface display of ClyA, the expression vectors for 193-aa immunogenic antigen of spike protein (termed S1E) from severe acute respiratory syndrome coronavirus (SARS-CoV) were constructed. The vectors carried a gene encoding S. typhi ClyA conjugated to S1E at the C terminus (termed ClyA-S1E) and asd gene in pGEM-T and pBR322, named pGApLCS1E and pBApLCS1E, respectively. An asd-mutated E. coli transformed with these vectors could grow without diaminopimelic acid (DAP), indicating that they were stably maintained in such mutants. ClyA-S1E recombinant proteins from these vectors were expressed on the surface of the attenuated S. typhimurium deficient of global virulence gene regulator, ppGpp. However, they did not show the hemolytic activity on the blood agar plate and cytotoxicity against HeLa cells. To examine whether bacteria expressing ClyA-S1E induced the immune response against S1E, S. typhimurium deficient of ppGpp and Asd was transformed with these vectors and orally immunized in mice. In the western blotting against GST-conjugated S1E using the immunized mouse sera, it was shown that the significant band was detected in the mouse serum by the bacteria transformed with pGApLCS1E but not with pBApLCS1E. It indicates that the immune response producing antibody was dependent on the expression level of ClyA-S1E. Therefore, ClyA delivery system can be used for SARS vaccine development.

Prognostic Value of T Cell Immunoglobulin Mucin-3 in Prostate Cancer

Piao, Yong-Rui,Piao, Long-Zhen,Zhu, Lian-Hua,Jin, Zhe-Hu,Dong, Xiu-Zhe Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.6

Background: Optimal treatment for prostate cancer remains a challenge worldwide. Recently, T cell immunoglobulin mucin-3 (TIM-3) has been implicated in tumor biology but its contribution prostate cancer remains unclear. The aim of this study was to investigate the role of TIM-3 as a prognostic marker in patients with prostate cancer. Methods: TIM-3 protein expression was determined by immunohistochemistry and Western blotting in 137 prostate cancer tumor samples and paired adjacent benign tissue. We also performed cell proliferation assays using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl- 2H tetrazolium bromide (MTT) and cell invasion assays. The effects of small interfering RNA (siRNA)-mediated knockdown of TIM-3 (TIM-3 siRNA) in two human prostate cancer cell lines were also evaluated. Results: TIM-3 expression was higher in prostate cancer tissue than in the adjacent benign tissue (P<0.001). High TIM-3 expression was an independent predictor of both recurrence-free survival and progression-free survival. TIM-3 protein was expressed in both prostate cancer cell lines and knockdown suppressed their proliferation and invasion capacity. Conclusions: TIM-3 expression is associated with a poor prognosis in prostate cancer. Taken together, our resutlts indicate that TIM-3 is a potential prognostic marker in prostate cancer.

Neuroprotective Effect of Wogonin: Potential Roles of Inflammatory Cytokines

Piao, Hua-Zi,Jin, Shun-Ai,Chun, Hyang-Sook,Lee, Jae-Chul,Kim, Won-Ki The Pharmaceutical Society of Korea 2004 Archives of Pharmacal Research Vol.27 No.9

Wogonin (5,7-dihydroxy-8-methoxyflavone), an active component originated from the root of Scutellaria baicalensis Georgi, has been reported to possess antioxidant and anti-inflamma-tory properties. In this study, we investigated the neuroprotective effect of wogonin in a focal cerebral ischemia rat model. Wogonin markedly reduced the infarct volume after 2 h middle cerebral artery occlusion followed by 22 h reperfusion. Wogonin decreased the production of nitric oxide and inflammatory cytokines such as TNF-$\alpha$ and IL-6 in lipopolisaccharide-stimu-lated microglial cells. While wogonin reduced the activity of NF-$textsc{k}$B, it did not change the activ-ity of mitogen-activated protein kinases family members, p38, ERK and JNK. The lipopolisaccharide-stimulated production of NO and cytokines was significantly blocked by vari-ous kinds of NF-$textsc{k}$B inhibitors such as N-acetyl cysteine, pyrrolidinedithiocarbamate and MG-132. The data may indicate that wogonin has neuroprotective effect by preventing the over-activation of microglial cells, possibly by inactivating NF-$textsc{k}$B signaling pathway

Metabolite profiling of gypenoside LVI in rat after oral and intravenous administration

Dao-Jin Chen,Hua-Gang Hu,Shao-Fang Xing,Huimin Liu,Xiang-Lan Piao 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.6

Gypenoside LVI, one of the major bioactivetriterpene saponins in Gynostemma pentaphyllum, has beenregarded as a potential and promising lead drug for antitumorstrategy. To better understand the pharmacologicalactivities of the component, an investigation of its in vivometabolism is important and necessary. In the presentstudy, a liquid chromatography-ion trap time of flighttandem mass spectrometry has been utilized to discoverand identify the metabolites of gypenoside LVI in rat urineafter oral and intravenous administration. Negative electrosprayionisation mass spectrometry was used to discerngypenoside LVI and its possible metabolites in urinesamples. As a result, after oral and intravenous administration,eight and six metabolites together with gypenosideLVI were detected and identified in rat urine, respectively. As metabolites of gypenoside LVI, they have never beenreported before. Deglycosylation and dehydration werefound to be the major metabolic processes of gypenosideLVI in rat.

Characterization and map-based cloning of the EP3 gene controlling panicle erectness in rice

Ri Hua Piao,Wen Zhu Jiang,Tae Ho Ham,Min Seon Choi,Yong Li Qiao,Sang Ho Chu,Jung Hyun Park,Mi Ok Woo,Zheng Xun Jin,Hee Jong Koh,Gyn Heung An,Joo Hyun Lee 한국육종학회 2009 한국육종학회 학술발표회 발표요지 Vol.41 No.1