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.

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.

Coronary Computed Tomography Angiography-Derived Fractional Flow Reserve in Patients with Anomalous Origin of the Right Coronary Artery from the Left Coronary Sinus

Chun Xiang Tang,Meng Jie Lu,Joseph Uwe Schoepf,Christian Tesche,Maximilian Bauer,John Nance,Parkwood Griffith,Guang Ming Lu,Long Jiang Zhang 대한영상의학회 2020 Korean Journal of Radiology Vol.21 No.2

Objective: To examine the fractional flow reserve derived from computed tomographic angiography (CT-FFR) in patients with anomalous origin of the right coronary artery from the left coronary sinus (R-ACAOS) with an interarterial course, assess the relationship of CT-FFR with the anatomical features of interarterial R-ACAOS on coronary computed tomographic angiography (CCTA), and determine its clinical relevance. Materials and Methods: Ninety-four patients with interarterial R-ACAOS undergoing CCTA were retrospectively included. Anatomic features (proximal vessel morphology [oval or slit-like], take-off angle, take-off level [below or above the pulmonary valve], take-off type, intramural course, % proximal narrowing area, length of narrowing, minimum luminal area [MLA] at systole and diastole, and vessel compression index) on CCTA associated with CT-FFR ≤ 0.80 were analyzed. Receiver operating characteristic analysis was performed to describe the diagnostic performance of CT-FFR ≤ 0.80 in detecting interarterial R-ACAOS. Results: Significant differences were found in proximal vessel morphology, take-off level, intramural course, % proximal narrowing area, and MLA at diastole (all p < 0.05) between the normal and abnormal CT-FFR groups. Take-off level, intramural course, and slit-like ostium (all p < 0.05) predicted hemodynamic abnormality (CT-FFR ≤ 0.80) with accuracies of 0.69, 0.71, and 0.81, respectively. Patients with CT-FFR ≤ 0.80 had a higher prevalence of typical angina (29.4% vs. 7.8%, p = 0.025) and atypical angina (29.4% vs. 6.5%, p = 0.016). Conclusion: Take-off level, intramural course, and slit-like ostium were the main predictors of abnormal CT-FFR values. Importantly, patients with abnormal CT-FFR values showed a higher prevalence of typical angina and atypical angina, indicating that CT-FFR is a potential tool to gauge the clinical relevance in patients with interarterial R-ACAOS.

Improved Control Strategy Based on Space Vectors for Suppressing Grid-Side Current Harmonics in Three-Phase Current Source Rectifiers with a Hybrid Switch

Xu, Yan,Lu, Guang-Xiang,Jiang, Li-Jie,Yi, Gui-Ping The Korean Institute of Power Electronics 2015 JOURNAL OF POWER ELECTRONICS Vol.15 No.2

This paper analyses the harmonic pollution to power grids caused by several high-power rectifiers, summarizes the requirements for rectifiers in suppressing grid-side current harmonics and optimizes a new-type of current source PWM rectifier with a hybrid switch. The rectifier with a hybrid switch boasts significant current characteristics and cost advantages in the high-power area. To further enhance the working frequency of the current source rectifier with a hybrid switch for suppressing grid-side harmonics and reducing the inductance size, this paper proposes an optimal control strategy based on space vector. It also verifies that the optimal control strategy based on space vector can reduce the total harmonic distortion of the grid-side current of the rectifier with a hybrid switch via circuit simulation and experimental results.

Improved Control Strategy Based on Space Vectors for Suppressing Grid-Side Current Harmonics in Three-Phase Current Source Rectifiers with a Hybrid Switch

Yan Xu,Guang-xiang Lu,Li-jie Jiang,Gui-Ping Yi 전력전자학회 2015 JOURNAL OF POWER ELECTRONICS Vol.15 No.2

This paper analyses the harmonic pollution to power grids caused by several high-power rectifiers, summarizes the requirements for rectifiers in suppressing grid-side current harmonics and optimizes a new-type of current source PWM rectifier with a hybrid switch. The rectifier with a hybrid switch boasts significant current characteristics and cost advantages in the high-power area. To further enhance the working frequency of the current source rectifier with a hybrid switch for suppressing grid-side harmonics and reducing the inductance size, this paper proposes an optimal control strategy based on space vector. It also verifies that the optimal control strategy based on space vector can reduce the total harmonic distortion of the grid-side current of the rectifier with a hybrid switch via circuit simulation and experimental results.

Dual Effect of Hepatic Macrophages on Liver Ischemia and Reperfusion Injury during Liver Transplantation

Tian-Fei Lu,Tai-Hua Yang,Cheng-Peng Zhong,Chuan Shen,Wei-Wei Lin,Guang-Xiang Gu,Qiang Xia,Ning Xu 대한면역학회 2018 Immune Network Vol.18 No.3

Ischemia-reperfusion injury (IRI) is a major complication in liver transplantation (LT) and it is closely related to the recovery of grafts' function. Researches has verified that both innate and adaptive immune system are involved in the development of IRI and Kupffer cell (KC), the resident macrophages in the liver, play a pivotal role both in triggering and sustaining the sterile inflammation. Damage-associated molecular patterns (DAMPs), released by the initial dead cell because of the ischemia insult, firstly activate the KC through pattern recognition receptors (PRRs) such as toll-like receptors. Activated KCs is the dominant players in the IRI as it can secret various pro-inflammatory cytokines to exacerbate the injury and recruit other types of immune cells from the circulation. On the other hand, KCs can also serve in a contrary way to ameliorate IRI by upregulating the anti-inflammatory factors. Moreover, new standpoint has been put forward that KCs and macrophages from the circulation may function in different way to influence the inflammation. Managements towards KCs are expected to be the effective way to improve the IRI.

Pemetrexed as a Component of First-, Second- and Third-line Chemotherapy in Treating Patients with Metastatic Lung Adenocarcinoma

Huang, Xin-En,Tian, Guang-Yu,Cao, Jie,Xu, Xia,Lu, Yan-Yan,Wu, Xue-Yan,Liu, Jin,Shi, Lin,Xiang, Jin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

Purpose: The current research was conducted to investigate the efficacy and safety of pemetrexed given continuously as a basement agent for first-, second- to third line chemotherapy of patients with metastatic lung adenocarcinoma. Patients and Methods: Patients with metastatic lung adenocarcinoma who were diagnosed in Jiangsu Cancer Hospital and Research Insitute, were enrolled. All received pemetrexed 500 $mg/m^2$ (intravenous; on day 1), and another chemotherapieutic agent every 3 weeks until disease progression, or intolerable toxicity. Then the patients were changed to a second line chemotherapy that was still based on pemetrexed 500 $mg/m^2$ and another chemotherapeutic agent differing from the first line example, until disease progression, or intolerable toxicity. When third line chemotherapy was needed, pemetrexed 500 $mg/m^2$ and another new chemotherapeutic agent were combined until disease progression. Evaluation of efficacy was conducted after two cycles of chemotherapy using the Response Evaluation Criteria for Solid Tumors. Toxicity was recorded according to NCI Criteria for Adverse Events version 3.0. Results: From January 2010 to September 2013, 15 patients were enrolled. Their median age was 56 years (range 43 to 77 years). Eight patients were male and 7 female. Five patients (33.3%) achieved PR, while 6 patients (40.0%) remained stable, no CR on first line; and 1 PR (7.7%), 5 stable (38.5%) were recorded when pemetrexed was ordered in second line; 5 patients (41.7%) were stable after pemetrexed was combined in third line; no complete response was observed. Main side effects were grade 1 to 2 neutrophil suppression and thrombocytopenia. Other toxicities included elevated transaminase and oral mucositis, but no treatment related death occurred. Conclusions: Pemetrexed continuously as a basement agent from first-, second- to third line chemotherapy is mildly effective in treating patients with metastatic lung adenocarcinoma with tolerable toxicity.

Comparison of Serum Tumor Associated Material (TAM) with Conventional Biomarkers in Cancer Patients

Shu, Jian,Li, Cheng-Guang,Liu, Yang-Chen,Yan, Xiao-Chun,Xu, Xu,Huang, Xin-En,Cao, Jie,Li, Ying,Lu, Yan-Yan,Wu, Xue-Yan,Liu, Jin,Xiang, Jin Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Objective: To compare expression level of serum tumor associated materials (TAM) with several conventional serum tumor biomarkers, eg., carcinoembryonic antigen (CEA), carbohydrate antigen19-9 (CA19-9), carbohydrate antigen 15-3 (CA15-3), alpha-fetoprotein(AFP), in selected solid tumors. Methods: Patients diagnosed histologically or cytologically with liver, breast, esophageal, gastric, colorectal or pancreatic cancers were enrolled into this study. After diagnosis, the level of TAM was determined by chemical colorimetry, and levels of conventional tumor markers was measured by chemiluminescence methods. Results: A total of 560 patients were enrolled into this study. No statistically significant difference was detected in TAM and the above mentioned tumor biomarkers in terms of their positivity and negativity ( P>0. 05). Conclusions: Detection of TAM in liver, breast, esophageal, gastric, colorectal, and pancreatic cancer patients demonstrates a good accordance with CEA, CA199, CA153, and AFP, thus suggesting that further study is warranted to verify whether TAM could be a surrogate for these conventional biomarkers.

Phase II Study on Safety and Efficacy of Yadanzi^® (Javanica oil emulsion injection) Combined with Chemotherapy for Patients with Gastric Cancer

Liu, Jin,Huang, Xin-En,Tian, Guang-Yu,Cao, Jie,Lu, Yan-Yan,Wu, Xue-Yan,Xiang, Jin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.3

Objective: To investigate the efficacy and safety of Yadanzi$^{(R)}$ (Javanica oil emulsion injection) combined with chemotherapy for treatment of patients with advanced gastric cancer. Methods: From January 2011 to December 2012, we recruited 75 patients with advanced gastric cancer, who received javanica oil emulsion injection together with chemotherapy. After two cycles of treatment, efficacy and safety of the combined therapies were evaluated. Results: Overall response rate of 75 patients after treatment was 85.3% (CR+PR+SD). Treatment related side effects were recorded. No treatment related death occurred. Conclusions: Javanica oil emulsion injection combined with chemotherapy could be considered as a safe and effective regimen in treating patients with advanced gastric cancer. Further randomized clinical trials should be conducted to confirm whether the addition of Yadanzi$^{(R)}$ to chemotheraphy could be associated with reduced toxicity, enhanced tolerability and improved quality of life for patients with advanced gastric cancer.

A Highly Active Alpha Amylase from Bacillus Licheniformis: Directed Evolution, Enzyme Characterization and Structural Analysis

( Yi Han Liu ),( Shu Ai Fan ),( Xiao Guang Liu ),( Zhi Meng Zhang ),( Jian Ling Wang ),( Zheng Xiang Wang ),( Fu Ping Lu ) 한국미생물 · 생명공학회 2014 Journal of microbiology and biotechnology Vol.24 No.7

The stability of Bacillus licheniformis alpha-amylase (BLA) under acid condition was enhanced through direct evolution using the error-prone polymerase chain reaction. One beneficial mutation site, H281I, was obtained in BLA. The specific activity of H281I was 161/352 U/mg, which was 62.6/27.5% higher than that of the wild-type (WT) (99/276 U/mg) at pH 4.5/6.5 and 95°C. The pH optimum for H281I was decreased about 1 unit, whereas no significant changes of optimum temperature and thermostability were observed compared with the wild type (WT). The kcat/Km value of H281I was 1.7-/1.4-fold higher at pH 4.5/6.5, respectively, than that of WT. The structure model analysis indicated that the H281I mutation altered the predicted interaction between the amino acid residues at 281 and 273, thus creating a conducive local environment for substrate binding, as reflected by its decreased Km, and consequently increased the specific activity.