Ginsenoside Rg3 in combination with artesunate overcomes sorafenib resistance in hepatoma cell and mouse models

Ying-Jie Chen,Jia-Ying Wu,Yu-Yi Deng,Ying Wu,Xiao-Qi Wang,Amy Sze-man Li,Lut Yi Wong,Xiuqiong Fu,Zhi-Ling Yu,Chun Liang 고려인삼학회 2022 Journal of Ginseng Research Vol.46 No.3

Sorafenib is effective in treating hepatoma, but most patients develop resistance to it. STAT3signaling has been implicated in sorafenib resistance. Artesunate (ART) and 20(R)-ginsenoside Rg3 (Rg3)have anti-hepatoma effects and can inhibit STAT3 signaling in cancer cells. This study aimed to evaluatethe effects of Rg3 in combination with ART (Rg3-plus-ART) in overcoming sorafenib resistance, and toexamine the involvement of STAT3 signaling in these effects. Methods: Sorafenib-resistant HepG2 cells (HepG2-SR) were used to evaluate the in vitro anti-hepatomaeffects of Rg3-plus-ART. A HepG2-SR hepatoma-bearing BALB/c-nu/nu mouse model was used to assessthe in vivo anti-hepatoma effects of Rg3-plus-ART. CCK-8 assays and Annexin V-FITC/PI double stainingwere used to examine cell proliferation and apoptosis, respectively. Immunoblotting was employed toexamine protein levels. ROS generation was examined by measuring DCF-DA fluorescence. Results: Rg3-plus-ART synergistically reduced viability of, and evoked apoptosis in HepG2-SR cells, andsuppressed HepG2-SR tumor growth in mice. Mechanistic studies revealed that Rg3-plus-ART inhibitedactivation/phosphorylation of Src and STAT3 in HepG2-SR cultures and tumors. The combination alsodecreased the STAT3 nuclear level and induced ROS production in HepG2-SR cultures. Furthermore, overactivation of STAT3 or removal of ROS diminished the anti-proliferative effects of Rg3-plus-ART, andremoval of ROS diminished Rg3-plus-ART's inhibitory effects on STAT3 activation in HepG2-SR cells. Conclusions: Rg3-plus-ART overcomes sorafenib resistance in experimental models, and inhibition of Src/STAT3 signaling and modulation of ROS/STAT3 signaling contribute to the underlying mechanisms. Thisstudy provides a pharmacological basis for developing Rg3-plus-ART into a novel modality for treatingsorafenib-resistant hepatoma.

Schisandrin B Improves the Hypothermic Preservation of Celsior Solution in Human Umbilical Cord Mesenchymal Stem Cells

Zhang Ying,Wang Peng,Jin Mei-xian,Zhou Ying-qi,Ye Liang,Zhu Xiao-juan,Li Hui-fang,Zhou Ming,Li Yang,Li Shao,Liang Kang-yan,Wang Yi,Gao Yi,Pan Ming-xin,Zhou Shu-qin,Peng Qing 한국조직공학과 재생의학회 2023 조직공학과 재생의학 Vol.20 No.3

BACKGROUND: Human umbilical cord mesenchymal stem cells (hUCMSCs) have emerged as promising therapy for immune and inflammatory diseases. However, how to maintain the activity and unique properties during cold storage and transportation is one of the key factors affecting the therapeutic efficiency of hUCMSCs. Schisandrin B (SchB) has many functions in cell protection as a natural medicine. In this study, we investigated the protective effects of SchB on the hypothermic preservation of hUCMSCs. METHODS: hUCMSCs were isolated from Wharton’s jelly. Subsequently, hUCMSCs were exposed to cold storage (4 C) and 24-h re-warming. After that, cells viability, surface markers, immunomodulatory effects, reactive oxygen species (ROS), mitochondrial integrity, apoptosis-related and antioxidant proteins expression level were evaluated. RESULTS: SchB significantly alleviated the cells injury and maintained unique properties such as differentiation potential, level of surface markers and immunomodulatory effects of hUCMSCs. The protective effects of SchB on hUCMSCs after hypothermic storage seemed associated with its inhibition of apoptosis and the anti-oxidative stress effect mediated by nuclear factor erythroid 2–related factor 2 signaling. CONCLUSION: These results demonstrate SchB could be used as an agent for hypothermic preservation of hUCMSCs.

The Beneficial Effects of Electroacupuncture at PC6 Acupoints (Neiguan) on Myocardial Ischemia in ASIC3 / mice

Ying-Wang,Yi-guo Chen,Wan-shuang Zhao,Di Li,Ya-han Xu,Meng-di Li,Jin Chen,Zhi-jun Kou,Qi-ge Wang,Nsoa dimitri Joseph 사단법인약침학회 2018 Journal of Acupuncture & Meridian Studies Vol.11 No.3

This study aims to investigate the possible mechanisms of electroacupuncture (EA) at PC6to improve myocardial ischemia (MI) by regulating the cardiac transient outward potassiumcurrent channel (Ito). According to the random number table, the mice were dividedinto six groups of six mice each: control group, MI group, PC6, LU7 (Lieque-point), ST36(Zusanli-point), and nonacupoint group. Mice in the control group were injected with saline(20 mg/kg, 24 hours interval), and the other ASIC3 / mice were injected subcutaneouslytwice with isoproterenol (ISO) (20 mg/kg, 24 hours interval). In thepreexperiment, 5 mg/kg, 10 mg/kg, 20 mg/kg, and 30 mg/kg of ISO were used, andthe results showed that 5 mg/kg and 10 mg/kg of ISO both could induce acute MI, butshorter duration of sustained MI. On the other hand, an injection of 30 mg/kg can makethe mice experience arrhythmia or die immediately, and EA was operated at PC6, LU7,ST36 acupoints, and nonacupoint in the mice of PC6, LU7, ST36, and nonacupoint groups,respectively, after injecting twice. Then Western blotting techniques (Western Blot) wereused to analyze the protein expressions of Kv1.4, Kv4.2, Kv4.3, and KchIP2. The results ofthis experiment showed that the protein expressions of Kv1.4, Kv4.2, Kv4.3, and KChIP2 inMI group were significantly lower than those in the control group (p < 0.01). Comparedwith MI group, the results of PC6, LU7, and ST36 groups obviously increased (p < 0.05). Furthermore, the expressions of PC6 group were higher than LU7 group and ST36 group(p < 0.05). And electrocardiogram’s T-waves showed obvious pathological changes inthe MI group compared to the control group (p < 0.01). After EA, the abnormal T-waves voltage of ECG in PC6, LU7, and ST36 groups was improved (p < 0.05). In addition, therate change of PC6 group was larger than that of both LU7 and ST36 groups (p < 0.05). But the T-waves voltage of the nonacupoint group was not significantly different than thatof the MI group (p > 0.05).

Weight Gain in Pregnancy, Maternal Age and Gestational Age in Relation to Fetal Macrosomia

( Yi Li ),( Qi-fei Liu ),( Dan Zhang ),( Ying Shen ),( Kui Ye ),( Han-lin Lai ),( Hai-qing Wang ),( Chuan-lai Hu ),( Qi-hong Zhao ),( Li Li ) 한국임상영양학회 2015 Clinical Nutrition Research Vol.4 No.2

To investigate the possible risk factors related to macrosomia. Pregnant women and their newborns (n = 1041) were recruited from a cohort study in Maternal and Child Care Center of Hefei from January 2011 to July 2012. Questionnaires were applied to collect the demographic data besides the medical records. Detailed health records of the entire pregnancy were obtained using retrospective study. Meanwhile the data of neonatal outcomes was prospectively tracked. Associations between exposure risk factors and macrosomia were analyzed using Pearson’s chi squared test. Logistic regression models were used to assess the independent association between these potential predictors and macrosomia. The incidence of macrosomia of this cohort was 11.24% of which male: female = 2.55:1. Male incidence (8.07%) of macrosomia was higher than female (3.17%), p < 0.001. Body mass index (BMI) before pregnancy (pre-BMI), maternal height, parity were not independently associated with macrosomia; multiple logistic regression analysis indicated that macrosomia was mainly independently associated with weight gain in pregnancy (OR=1.14,95% CI [1.10-1.19]), maternal age (OR = 1.09,95% CI [1.03-1.15]) and gestational age (OR = 1.62,95% CI [1.31-1.99]), respectively. Our findings indicate that weight gain in pregnancy, maternal age and gestational age should be considered as independent risk factors for macrosomia.

CADMIUM TELLURIDE NANOCRYSTALS: SYNTHESIS, GROWTH MODE AND EFFECT OF REACTION TEMPERATURE ON CRYSTAL STRUCTURES

XIAO-YING QI,KAN-YI PU,QU-LI FAN,DUO-FENG TANG,GUI-AN WEN,FREDDY Y. C. BOEY,LIAN-HUI WANG,WEI HUANG,HUA ZHANG 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2008 NANO Vol.3 No.2

A series of cadmium telluride (CdTe) nanocrystals were synthesized by a modified organometallic synthesis method at various reaction temperatures ranging from 130 to 250°C. In this method, octadecylamine (ODA) was introduced as an additional coordinating component to the mixture of trioctylphosphine oxide (TOPO) and trioctylphosphine (TOP). CdO was used as a precursor. The prepared CdTe nanocrystals were studied by the absorption and emission spectra as well as the powder X-ray diffraction (XRD) patterns. The result shows that besides the traditional continuous-growth mode observed frequently at relatively high reaction temperature, a discontinuous-growth mode was confirmed at the initial growth stage of CdTe nanocrystals, arising from the change of the absorption spectra of CdTe nanocrystals with the reaction time at relatively low reaction temperature. The structures of CdTe nanocrystals, e.g., the cubic zinc blende structure at 160°C and the hexagonalwurtzite structure at 250°C, were characterized by XRD.

Glutamine-Supplemented Parenteral Nutrition and Probiotics in Four Adult Autoimmune Enteropathy Patients

( Ren Ying Xu ),( Yan Ping Wan ),( Yi Quan Zhou ),( Li Ping Lu ),( Zhi Qi Chen ),( Ying Jie Wu ),( Wei Cai ) 대한소화기학회 2014 Gut and Liver Vol.8 No.3

To evaluate the effects of glutamine-supplemented parenteral nutrition (PN) and probiotics in adult autoimmune enteropathy (AIE) patients. Four adult AIE patients were identified from April 2006 to January 2012. Clinical and nutritional data were obtained from the patients’ medical records. Glutamine-supplemented PN started immediately when the AIE diagnosis was confirmed. The total PN duration was 351 days. According to the PN prescription, the average caloric intake ranged from 20 to 25 kcal/kg/day, and the protein intake ranged from 1.2 to 1.5 g/kg/day. Alanyl-glutamine (20 g/day) was administered to AIE patients for 4 weeks followed by a 2-week break, and this treatment schedule was repeated when PN lasted for more than 6 weeks. Body weight gain and an increased serum albumin level were achieved after PN, and defecation frequency and quality also improved. Each patient received oral supplements, 250 mL of Ensure and two probiotics capsules (each capsule containing 0.5×108 colonies) three times a day when enteral nutrition started. Three AIE patients were successfully weaned off PN, and one patient died of pneumonia. Glutamine-supplemented PN and probiotics show promise in managing patients with AIE and related malnutrition.

siRNA-mediated Silencing of Notch-1 Enhances Docetaxel Induced Mitotic Arrest and Apoptosis in PCa Cells

Ye, Qi-Fa,Zhang, Yi-Chuan,Peng, Xiao-Qing,Long, Zhi,Ming, Ying-Zi,He, Le-Ye Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.6

Purpose: Notch is an important signaling pathway that regulates cell fate, stem cell maintenance and the initiation of differentiation in many tissues. It has been reported that activation of Notch-1 contributes to tumorigenesis. However, whether Notch signaling might have a role in chemoresistance of prostate cancer is unclear. This study aimed to investigate the effects of Notch-1 silencing on the sensitivity of prostate cancer cells to docetaxel treatment. Methods: siRNA against Notch-1 was transfected into PC-3 prostate cancer cells. Proliferation, apoptosis and cell cycle distribution were examined in the presence or absence of docetaxel by MTT and flow cytometry. Expression of $p21^{waf1/cip1}$ and Akt as well as activation of Akt in PC-3 cells were detected by Western blot and Real-time PCR. Results: Silencing of Notch-1 promoted docetaxel induced cell growth inhibition, apoptosis and cell cycle arrest in PC-3 cells. In addition, these effects were associated with increased $p21^{waf1/cip1}$ expression and decreased Akt expression and activation in PC-3 cells. Conclusion: Notch-1 promotes chemoresistance of prostate cancer and could be a potential therapeutic target.

Glycididazole Sodium Combined with Radiochemotherapy for Locally Advanced Nasopharyngeal Carcinoma

Li, Ming-Yi,Liu, Jin-Quan,Chen, Dong-Ping,Qi, Bin,Liang, Yu-Ying,Yin, Wen-Jing Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.6

Background: To evaluate efficacy and side effects of glycididazole sodium (CMNa) combined with chemotherapy (cisplatin plus 5-FU/folic acid, PLF) and radiotherapy in treating patients with locally advanced nasopharyngeal carcinoma. Materials and Methods: Patients with III~IV stage nasopharyngeal carcinoma (NPC),were randomly divided into treatment group (46 patients) and control group (45 patients). Both groups received radiotherapy concomitant with PLF chemotherapy. The treatment group at the same time cwas given CMNa ($800mg/m^2$ before radiotherapy), by l h intravenous drip, three times a week. Results: When the dose of radiation was over 60 Gy, complete response rates of nasopharyngeal tumor and lymph node metastases in treatment group were significantly higher than in the control group (93.5% vs 77.8%; 89.1% vs 93.5%, p<0.05). Three months after radiotherapy, complete response rate of nasopharynx cancer and lymph node metastases in treatment group was both 97.8%, again higher than in the control group (84.4% and 82.2%) (p<0.05). In the treatment group, 1, 3, 5 year disease-free survival rates were 95.7%, 86.7% and 54.5%; and in control group, the corresponding disease-free survival rates were 93.3%, 66.2% and 38.6%, respectively, the difference being statistically significant (log-rank =5.887, p=0.015). One, 3, 5 year overall survival rates in two groups of patients were 97.8%, 93.5%, 70.4% and 95.5%, 88.07%, 48.4%, respectively, again with a statistically significant difference (log-rank=6.470, p=0.011). Acute toxicity and long-term radiotherapy related toxicity in the two groups did not differ (p>0.05). Conclusions: Glycididazole sodium could improve curative effects without increasing adverse reactions when treating paitents with locally advanced nasopharyngeal carcinoma.

Construction of a Transposon-mediated Baculovirus Vector Hanpvid and a New Cell Line for Expressing Barnase

( Qin Qin ),( Ying Le Liu ),( Ying Zhu ),( Shun Yi Li ),( Yi Peng Qi ) 생화학분자생물학회 2005 BMB Reports Vol.38 No.1

In this study we developed the transposon-mediated shuttle vector `Hanpvid`, which composed of HaNPV (Heliothis armigera nuclear polyhedrosis virus) genomic DNA and a transposon cassette from Bacmid of Bac-to-Bac system. Hanpvid replicates in E. coli in the same way as Bacmid and retains infective function in cotton bollworm cells (Hz-AMU). Using Hanpvid we constructed a recombinant virus, which could infect Hz-AM1 cells and generate recombinant HaNPV (rHa-Bar) containing the barnase gene, a ribonuclease gene from Bacillus amyloliquefaciens. Since the expression vector carrying barnase gene cannot replicate in the absence of barstar, a specific inhibitor of barnase, we constructed a new cotton bollworm cell line (AMl-NB) using the marker rescue method. In AM1-NB barstar was integrated into the cellular chromosome to sustain the replication of rHa-Bar. To screen out recombinant HaNPV for potential use as biopesticide, Hz-AM! and AM1-NB cell lines were infected with rHa-Bar, respectively. The results obtained indicate that Viral progenies in AM1-NB were 23 and 160 times greater than those in Hz-AM1 48 h and 72 h after infection, respectively. With additional insertion of the polyhedron gene from AcNPV (Autographa californica nuclear polyhedrosis virus) into the Hanpvid genome, rHa-Bar regained the polyhedron phenotype and its pest-killing rate greatly improved. Toxic analysis showed that the lethal dosages (LD_(50)) and the lethal time(s) (LT_(50)) of rHa-Bar were reduced by 20% and 30%, respectively, compared to wt-HaNPV in the third instar larvae of cotton bollworm. This study shows that in AM1-NB barnase can be effectively produced and used as pest-killing agent for the biological control of cotton pests.

Elevated Expression of Nuclear Protein Kinase CK2α as a Poor Prognosis Indicator in Lymph Node Cancerous Metastases of Human Thyroid Cancers

Guo, Miao,Liu, Chao,Qi, Feng-Jie,Zhang, Xiu-Mei,Ren, Li-Li,Liu, Yi-Meng,Meng, Zhi-Chao,Zhu, Zhi-Tu,Xiao, Jian-Ying Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.17

Aim: To investigate the expression of protein kinase $CK2{\alpha}$ ($CK2{\alpha}$) in human thyroid disease and its relationship with thyroid cancer metastasis. Materials and Methods: Using immunohistochemistry we measured the expression of $CK2{\alpha}$ in 76 benign and malignant human thyroid cancer tissues, including 10 pairs of papillary carcinoma tissues with or without lymph node cancerous metastasis and similarly 10 pairs of lymph nodes. Results: The expression of $CK2{\alpha}$ was found to be higher in thyroid carcinoma cases (papillary carcinoma, follicular carcinoma, anaplastic carcinoma and medullary carcinoma) than in ones such as chronic lymphocytic thyroiditis, nodular goiter and adenoma. These findings were also confirmed by RT-PCR and Western blotting. More strikingly, elevated expression of $CK2{\alpha}$ in thyroid papillary carcinoma tissues was not only significantly associated with lymph node cancerous metastasis and clinical stage of thyroid cancers; but also correlated with epithelial-mesenchymal transition (EMT) and high tenascin C (TNC) expression. In addition, EMT and high TNC expression in thyroid carcinoma tissues was significantly associated with lymph node cancerous metastasis. Conclusions: Elevated expression of nuclear $CK2{\alpha}$ is a poor prognosis indicator in lymph node cancerous metastasis of human thyroid cancers.