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Stem-leaf saponins from Panax notoginseng counteract aberrant autophagy and apoptosis in hippocampal neurons of mice with cognitive impairment induced by sleep deprivation

  • Cao, Yin;Yang, Yingbo;Wu, Hui;Lu, Yi;Wu, Shuang;Liu, Lulu;Wang, Changhong;Huang, Fei;Shi, Hailian;Zhang, Beibei;Wu, Xiaojun;Wang, Zhengtao
    • Journal of Ginseng Research
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    • v.44 no.3
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    • pp.442-452
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    • 2020
  • Backgroud: Sleep deprivation (SD) impairs learning and memory by inhibiting hippocampal functioning at molecular and cellular levels. Abnormal autophagy and apoptosis are closely associated with neurodegeneration in the central nervous system. This study is aimed to explore the alleviative effect and the underlying molecular mechanism of stem-leaf saponins of Panax notoginseng (SLSP) on the abnormal neuronal autophagy and apoptosis in hippocampus of mice with impaired learning and memory induced by SD. Methods: Mouse spatial learning and memory were assessed by Morris water maze test. Neuronal morphological changes were observed by Nissl staining. Autophagosome formation was examined by transmission electron microscopy, immunofluorescent staining, acridine orange staining, and transient transfection of the tf-LC3 plasmid. Apoptotic event was analyzed by flow cytometry after PI/annexin V staining. The expression or activation of autophagy and apoptosis-related proteins were detected by Western blotting assay. Results: SLSP was shown to improve the spatial learning and memory of mice after SD for 48 h, accomanied with restrained excessive autophage and apoptosis, whereas enhanced activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway in hippocampal neurons. Meanwhile, it improved the aberrant autophagy and apoptosis induced by rapamycin and re-activated phosphoinositide 3-kinase/Akt/mammalian target of rapamycin signaling transduction in HT-22 cells, a hippocampal neuronal cell line. Conclusion: SLSP could alleviate cognitive impairment induced by SD, which was achieved probably through suppressing the abnormal autophagy and apoptosis of hippocampal neurons. The findings may contribute to the clinical application of SLSP in the prevention or therapy of neurological disorders associated with SD.

Neutrophil Count and the Inflammation-based Glasgow Prognostic Score Predict Survival in Patients with Advanced Gastric Cancer Receiving First-line Chemotherapy

  • Li, Qing-Qing;Lu, Zhi-Hao;Yang, Li;Lu, Ming;Zhang, Xiao-Tian;Li, Jian;Zhou, Jun;Wang, Xi-Cheng;Gong, Ji-Fang;Gao, Jing;Li, Jie;Li, Yan;Shen, Lin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.945-950
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    • 2014
  • Purpose: To explore the value of systemic inflammatory markers as independent prognostic factors and the extent these markers improve prognostic classification for patients with inoperable advanced or metastatic gastric cancer (GC) receiving palliative chemotherapy. Methods: We studied the prognostic value of systemic inflammatory factors such as circulating white blood cell count and its components as well as that combined to form inflammation-based prognostic scores (Glasgow Prognostic Score (GPS), Neutrophil-Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Prognostic Index (PI) and Prognostic Nutritional Index (PNI)) in 384 patients with inoperable advanced or metastatic gastric cancer (GC) receiving first-line chemotherapy. Univariate and multivariate analyses were performed to examine the impact of inflammatory markers on overall survival (OS). Results: Univariate analysis revealed that an elevated white blood cell, neutrophil and/or platelet count, a decreased lymphocyte count, a low serum albumin concentration, and high CRP concentration, as well as elevated NLR/PLR, GPS, PI, PNI were significant predictors of shorter OS. Multivariate analysis demonstrated that only elevated neutrophil count (HR 3.696, p=0.003) and higher GPS (HR 1.621, p=0.01) were independent predictors of poor OS. Conclusion: This study demonstrated elevated pretreatment neutrophil count and high GPS to be independent predictors of shorter OS in inoperable advanced or metastatic GC patients treated with first-line chemotherapy. Upon validation of these data in independent studies, stratification of patients using these markers in future clinical trials is recommended.

Weight Loss Correlates with Macrophage Inhibitory Cytokine-1 Expression and Might Influence Outcome in Patients with Advanced Esophageal Squamous Cell Carcinoma

  • Lu, Zhi-Hao;Yang, Li;Yu, Jing-Wei;Lu, Ming;Li, Jian;Zhou, Jun;Wang, Xi-Cheng;Gong, Ji-Fang;Gao, Jing;Zhang, Xiao-Tian;Li, Jie;Li, Yan;Shen, Lin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.15
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    • pp.6047-6052
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    • 2014
  • Background: Weight loss during chemotherapy has not been exclusively investigated. Macrophage inhibitory cytokine-1 (MIC-1) might play a role in its etiology. Here, we investigated the prognostic value of weight loss before chemotherapy and its relationship with MIC-1 concentration and its occurrence during chemotherapy in patients with advanced esophageal squamous cell carcinoma (ESCC). Materials and Methods: We analyzed 157 inoperable locally advanced or metastatic ESCC patients receiving first-line chemotherapy. Serum MIC-1 concentrations were assessed before chemotherapy. Patients were assigned into two groups according to their weight loss before or during chemotherapy:>5% weight loss group and ${\leq}5%$ weight loss group. Results: Patients with weight loss>5% before chemotherapy had shorter progression-free survival period (5.8 months vs. 8.7 months; p=0.027) and overall survival (10.8 months vs. 20.0 months; p=0.010). Patients with weight loss >5% during chemotherapy tended to have shorter progression-free survival (6.0 months vs. 8.1 months; p=0.062) and overall survival (8.6 months vs. 18.0 months; p=0.022), and if weight loss was reversed during chemotherapy, survival rates improved. Furthermore, serum MIC-1 concentration was closely related to weight loss before chemotherapy (p=0.001) Conclusions: Weight loss both before and during chemotherapy predicted poor outcome in advanced ESCC patients, and MIC-1 might be involved in the development of weight loss in such patients.

Cloning and Characterization of Ginsenoside-Hydrolyzing β-Glucosidase from Lactobacillus brevis That Transforms Ginsenosides Rb1 and F2 into Ginsenoside Rd and Compound K

  • Zhong, Fei-Liang;Ma, Rui;Jiang, Mingliang;Dong, Wei-Wei;Jiang, Jun;Wu, Songquan;Li, Donghao;Quan, Lin-Hu
    • Journal of Microbiology and Biotechnology
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    • v.26 no.10
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    • pp.1661-1667
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    • 2016
  • The ginsenoside-hydrolyzing β-glucosidase gene (bgy2) was cloned from Lactobacillus brevis. We expressed this gene in Escherichia coli BL21(DE3), isolated the resulting protein, and then utilized the enzyme for the biotransformation of ginsenosides. The bgy2 gene contains 2,223 bp, and encodes a protein of 741 amino acids that is a member of glycosyl hydrolase family 3. β-Glucosidase (Bgy2) cleaved the outer glucose moieties of ginsenosides at the C-20 position, and the inner glucose at the C-3 position. Under optimal conditions (pH 7.0, 30℃), we used 0.1 mg/ml Bgy2 in 20 mM sodium phosphate buffer (PBS) for enzymatic studies. In these conditions, 1.0 mg/ml ginsenoside Rb1 and ginsenoside F2 were converted into 0.59 mg/ml ginsenoside Rd and 0.72mg/ml compound K, with molar conversion productivities of 69% and 91%, respectively. In pharmaceutical and commercial industries, this recombinant Bgy2 would be suitable for producting ginsenoside Rd and compound K.

Surface-Displayed Porcine IFN-λ3 in Lactobacillus plantarum Inhibits Porcine Enteric Coronavirus Infection of Porcine Intestinal Epithelial Cells

  • Liu, Yong-Shi;Liu, Qiong;Jiang, Yan-Long;Yang, Wen-Tao;Huang, Hai-Bin;Shi, Chun-Wei;Yang, Gui-Lian;Wang, Chun-Feng
    • Journal of Microbiology and Biotechnology
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    • v.30 no.4
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    • pp.515-525
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    • 2020
  • Interferon (IFN)-λ plays an essential role in mucosal cells which exhibit strong antiviral activity. Lactobacillus plantarum (L. plantarum) has substantial application potential in the food and medical industries because of its probiotic properties. Alphacoronaviruses, especially porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV), cause high morbidity and mortality in piglets resulting in economic loss. Co-infection by these two viruses is becoming increasingly frequent. Therefore, it is particularly important to develop a new drug to prevent diarrhea infected with mixed viruses in piglets. In this study, we first constructed an anchored expression vector with CWA (C-terminal cell wall anchor) on L. plantarum. Second, we constructed two recombinant L. plantarum strains that anchored IFN-λ3 via pgsA (N-terminal transmembrane anchor) and CWA. Third, we demonstrated that both recombinant strains possess strong antiviral effects against coronavirus infection in the intestinal porcine epithelial cell line J2 (IPEC-J2). However, recombinant L. plantarum with the CWA anchor exhibited a more powerful antiviral effect than recombinant L. plantarum with pgsA. Consistent with this finding, Lb.plantarum-pSIP-409-IFN-λ3-CWA enhanced the expression levels of IFN-stimulated genes (ISGs) (ISG15, OASL, and Mx1) in IPEC-J2 cells more than did recombinant Lb.plantarum-pSIP-409-pgsA'-IFN-λ3. Our study verifies that recombinant L. plantarum inhibits PEDV and TGEV infection in IPEC-J2 cells, which may offer great potential for use as a novel oral antiviral agent in therapeutic applications for combating porcine epidemic diarrhea and transmissible gastroenteritis. This study is the first to show that recombinant L. plantarum suppresses PEDV and TGEV infection of IPEC-J2 cells.

Physiological response of red macroalgae Pyropia yezoensis (Bangiales, Rhodophyta) to light quality: a short-term adaptation

  • Xuefeng Zhong;Shuai Che;Congying Xie;Lan Wu;Xinyu Zhang;Lin Tian;Chan Liu;Hongbo Li;Guoying Du
    • ALGAE
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    • v.38 no.2
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    • pp.141-150
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    • 2023
  • Light quality is a common environmental factor which influences the metabolism of biochemical substances in algae and leads to the response of algal growth and development. Pyropia yezoensis is a kind of economic macroalgae that naturally grows in the intertidal zone where the light environment changes dramatically. In the present study, P. yezoensis thalli were treated under white light (control) and monochromatic lights with primary colors (blue, green, and red) for 14 days to explore their physiological response to light quality. During the first 3 days of treatment, P. yezoensis grew faster under blue light than other light qualities. In the next 11 days, it showed better adaptation to green light, with higher growth rate and photosynthetic capacity (reflected by a higher rETRmax = 61.58 and Ek = 237.78). A higher non-photochemical quenching was observed in the treatment of red light than others for 14 days. Furthermore, the response of P. yezoensis to light quality also results in the difference of photosynthetic pigment contents. The monochromatic light could reduce the synthesis of all pigments, but the reduction degree was different, which may relate to the spectral absorption characteristics of pigments. It was speculated that P. yezoensis adapted to a specific or changing light environments by regulating the synthesis of pigments to achieve the best use of light energy in photosynthesis and premium growth and metabolism.

Dynamics of fungal community during silage fermentation of elephant grass (Pennisetum purpureum) produced in northern Vietnam

  • Vu, Viet Ha;Li, Xiyang;Wang, Mengyuan;Liu, Rongmei;Zhang, Guojian;Liu, Wei;Xia, Baixue;Sun, Qun
    • Asian-Australasian Journal of Animal Sciences
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    • v.32 no.7
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    • pp.996-1006
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    • 2019
  • Objective: This study aimed to gain deeper insights into the dynamic changes in spoilage fungi populations during fermentation and the influence of traditional additives on silage quality. Methods: Elephant grass (Pennisetum purpureum) was prepared without any additive (control), and with the addition of 0.5% salt, and 0.5% salt-0.2% sugar mixture. The fungal community was then determined using a classic culturing method and high-throughput sequencing at 0, 5, 15, and 60 days after ensiling. Results: The results showed that the fungal community of elephant grass silage varied significantly between the natural fermentation without any additive and the two additive groups. The diversity and relative abundance of spoilage molds in the control group were much higher than those in the two treatment groups (p<0.05). Three species of yeasts (Candida sp., Pichia sp., Trichosporon sp.) and four spoilage molds (Fusarium sp., Aspergillus sp., Muco sp. and Penicillin sp.) were the predominant fungi in elephant grass during natural fermentation from 0 to 60 days, which were found to be significantly decreased in salt and sugar additive groups (p<0.05). Meanwhile, the diversity and relative abundance of undesirable molds in the 0.5%-salt additive group were the lowest among all groups. Conclusion: Adding salt and sugar, particularly 0.5% salt, is a promising effective approach to reduce the amount of undesirable fungi thus, improving the silage quality of elephant grass in northern Vietnam.

CK2 phosphorylates AP-2α and increases its transcriptional activity

  • Ren, Kaiqun;Xiang, Shuanglin;He, Fangli;Zhang, Wenfeng;Ding, Xiaofeng;Wu, Yanyang;Yang, Liping;Zhou, Jianlin;Gao, Xiang;Zhang, Jian
    • BMB Reports
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    • v.44 no.7
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    • pp.490-495
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    • 2011
  • Transcription factor AP-$2{\alpha}$ involves in the process of mammalian embryonic development and tumorigenesis. Many studies have shown that AP-$2{\alpha}$ functions in association with other interacting proteins. In a two-hybrid screening, the regulatory subunit ${\beta}$ of protein casein kinase 2 ($CK2{\beta}$) was identified as an interacting protein of AP-$2{\alpha}$; we confirmed this interaction using in-vitro GST pull-down and in-vivo co-immunoprecipitation assays; in an endogenous co-immunoprecipitation experiment, we further found the catalytic subunit ${\alpha}$ of protein casein kinase 2 ($CK2{\alpha}$) also exists in the complex. Phosphorylation analysis revealed that AP-$2{\alpha}$ was phosphorylated by CK2 kinase majorly at the site of Ser429, and such phosphorylation could be blocked by CK2 specific inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) in a dose-dependent manner. Luciferase assays demonstrated that both $CK2{\alpha}$ and $CK2{\beta}$ enhanced the transcription activity of AP-$2{\alpha}$; moreover, $CK2{\beta}$ increased the stability of AP-$2{\alpha}$. Our data suggest a novel cellular function of CK-2 as a transcriptional co-activator of AP-$2{\alpha}$.

Biotransformation of Panax ginseng extract by rat intestinal microflora: identification and quantification of metabolites using liquid chromatography-tandem mass spectrometry

  • Dong, Wei-Wei;Zhao, Jinhua;Zhong, Fei-Liang;Zhu, Wen-Jing;Jiang, Jun;Wu, Songquan;Yang, Deok-Chun;Li, Donghao;Quan, Lin-Hu
    • Journal of Ginseng Research
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    • v.41 no.4
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    • pp.540-547
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    • 2017
  • Background: In general, after Panax ginseng is administered orally, intestinal microbes play a crucial role in its degradation and metabolization process. Studies on the metabolism of P. ginseng by microflora are important for obtaining a better understanding of their biological effects. Methods: In vitro biotransformation of P. ginseng extract by rat intestinal microflora was investigated at $37^{\circ}C$ for 24 h, and the simultaneous determination of the metabolites and metabolic profile of P. ginseng saponins by rat intestinal microflora was achieved using LC-MS/MS. Results: A total of seven ginsenosides were detected in the P. ginseng extract, including ginsenosides Rg1, Re, Rf, Rb1, Rc, Rb2, and Rd. In the transformed P. ginseng samples, considerable amounts of deglycosylated metabolite compound K and Rh1 were detected. In addition, minimal amounts of deglycosylated metabolites (ginsenosides Rg2, F1, F2, Rg3, and protopanaxatriol-type ginsenosides) and untransformed ginsenosides Re, Rg1, and Rd were detected at 24 h. The results indicated that the primary metabolites are compound K and Rh1, and the protopanaxadiol-type ginsenosides were more easily metabolized than protopanaxatriol-type ginsenosides. Conclusion: This is the first report of the identification and quantification of the metabolism and metabolic profile of P. ginseng extract in rat intestinal microflora using LC-MS/MS. The current study provided new insights for studying the metabolism and active metabolites of P. ginseng.

Combined Expression of Metastasis Related Markers Naa10p, SNCG and PRL-3 and its Prognostic Value in Breast Cancer Patients

  • Min, Li;Ma, Ruo-Lan;Yuan, Hua;Liu, Cai-Yun;Dong, Bing;Zhang, Cheng;Zeng, Yan;Wang, Li;Guo, Jian-Ping;Qu, Li-Ke;Shou, Cheng-Chao
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.7
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    • pp.2819-2826
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    • 2015
  • Combinations of multiple biomarkers representing distinct aspects of metastasis may have better prognostic value for breast cancer patients, especially those in late stages. In this study, we evaluated the protein levels of N-${\alpha}$-acetyltransferase 10 protein (Naa10p), synuclein-${\gamma}$ (SNCG), and phosphatase of regenerating liver-3 (PRL-3) in 365 patients with breast cancer by immunohistochemistry. Distinct prognostic subgroups of breast cancer were identified by combination of the three biomarkers. The Naa10p+SNCG-PRL-3-subgroup showed best prognosis with a median distant metastasis-free survival (DMFS) of 140 months, while the Naa10p-SNCG+PRL-3+subgroup had the worst prognosis with a median DMFS of 60.5 months. Multivariate analysis indicated Naa10p, SNCG, PRL-3, and the TNM classification were all independent prognostic factors for both DMFS and overall survival (OS). The three biomarker combination of Naa10p, SNCG and PRL-3 performed better in patients with lymph node metastasis, especially those with more advanced tumors than other subgroups. In conclusion, the combined expression profile of Naa10p, SNCG and PRL-3, alone or in combination with the TNM classification system, may provide a precise estimate of prognosis of breast cancer patients.