Pterostilbene Protects Against Lipopolysaccharide/D-Galactosamine-Induced Acute Liver Failure by Upregulating the Nrf2 Pathway and Inhibiting NF-κB, MAPK, and NLRP3 Inflammasome Activation

Erli Zhang,Jingbo Huang,Kun Wang,Qinlei Yu,Chao Zhu,Hua Ren 한국식품영양과학회 2020 Journal of medicinal food Vol.23 No.9

The purpose of this study was to evaluate the protective effect of pterostilbene (Psb) against lipopolysaccharide and D-galactosamine (L/D)-induced acute liver failure (ALF) in mice and its potential mechanisms. Histology of liver was detected by H&E staining. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in serum and malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH), and superoxide dismutase (SOD) contents in liver were examined using detection kits. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) secretion were detected by ELISA. Meanwhile, MAPK, NF-κB, NLRP3 inflammasome, and Nrf2 were assessed by western blotting. Our findings showed that pretreatment with Psb protected against L/D-induced ALF by lowering the lethality, improving liver histology, reducing ALT, AST, IL-6, IL-1β, TNF-α, MDA, and MPO levels, and boosting liver GSH content and SOD activity. Moreover, Psb pretreatment effectively suppressed inflammation by decreasing NLRP3 inflammasome, MAPK, and NF-κB pathway activations. Moreover, Psb pretreatment efficiently enhanced the expression of several antioxidant enzymes, mainly depending on Nrf2 activation. This was the first study to demonstrate that Psb protects against L/D-induced ALF by inactivating MAPK, NF-κb, and NLRP3 inflammasome and upregulating the Nrf2 signaling pathway, indicating a potential therapeutic application for ALF treatment.

Study of anti-inflammatory activities of a-D-glucosylated eugenol

Peng Zhang,Erli Zhang,Min Xiao,Weijian Xu,Chang Chen 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.1

Inflammation is an immune response against avariety of noxious stimuli, such as infection, chemicals,and physical injury. Eugenol, a natural phenolic extract,has drawn much attention for its various desirable pharmacologicalfunctions and is, therefore, broadly used in ourdaily life and medical practice. However, further usage ofeugenol is greatly limited due to its unwanted properties,such as physicochemical instability, poor solubility, andhigh-dose cytotoxicity. In hopes of extending its applicabilitythrough glycosylation, we previously reported anovel, efficient, and high throughput way to biosynthesizea-D-glucosylated eugenol (a-EG). In this study, we furtherexplored the potential superior properties of a-EG to itsparent eugenol in terms of anti-inflammatory activities. Wedemonstrated that a-EG was an effective anti-inflammatorymediator in both non-cellular and cellular environments. In addition, the non-cellular inhibitory effect of a-EGcould be amplified by a-glucosidase, which ubiquitouslyexists in cytoplasm. Furthermore, a-EG exhibited a superior anti-inflammatory effect to its parent eugenol in a cellularenvironment. In words, our findings collectively suggest thata-EG is a stronger anti-inflammatory mediator and maythereby serve as a desirable substitute for eugenol and apotential therapeutic prodrug in treating inflammatory diseasesin the future.

Functional RsaI/PstI Polymorphism in Cytochrome P450 2E1 Contributes to Bladder Cancer Susceptibility: Evidence from a Meta-analysis

Deng, Xiao-Dong,Gao, Qin,Zhang, Bo,Zhang, Li-Xia,Zhang, Wei,Er, Zhe-Er Mu,Xie, Ying,Ma, Ying,Liu, Yun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.12

Background: Cytochrome P450 2E1 (CYP2E1) might be involved in the development of bladder cancer. However, previous studies of any association between CYP2E1 RsaI/PstI polymorphism and bladder cancer risk have yielded conflicting results. In this study, we performed a more precise estimation of the relationship by a meta-analysis based on the currently available evidence from the literature. Method: To assess the effect of CYP2E1 RsaI/PstI polymorphism on bladder cancer susceptibility, a meta-analysis of 6 available studies with 1,510 cases and 1,560 controls were performed through Feb 2014. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to estimate the strength of association for CYP2E1 RsaI/PstI polymorphism under different genetic models. Results: When available studies were pooled into the meta-analysis, we found that the C1C2 and C2C2 genotypes of CYP2E1 RsaI/PstI polymorphism significantly decreased bladder cancer risk under different genetic models (heterozygote: OR=0.766, 95%CI=0.613-0.957, $P_{OR}$=0.019; homozygote: OR=0.51, 95%CI=0.303-0.858, $P_{OR}$=0.011; dominant: OR=0.733, 95%CI=0.593-0.905, $P_{OR}$=0.004; recessive: OR=0.565, 95%CI=0.337-0.947, $P_{OR}$=0.030). Subgroup analysis indicated that C2C2 genotype was significantly associated with decreased bladder cancer risk under the homozygote genetic model in Caucasians. There was no evidence of heterogeneity or publication bias. Conclusions: The current meta-analysis suggested that the CYP2E1 RsaI/PstI polymorphism might be associated with bladder cancer susceptibility, especially in Caucasians. Further studies are needed to validate the above conclusion.

Human Papillomavirus Type 16/18 Oncoproteins: Potential Therapeutic Targets in Non-smoking Associated Lung Cancer

Zhang, Er-Ying,Tang, Xu-Dong Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.11

High-risk human papillomavirus (HPV) especially HPV-16 and HPV-18 types are speculated to be important risk factors in non-smoking associated lung cancer in Asia. Increasing evidence has demonstrated that HPV oncoproteins may contribute to lung tumorigenesis and cell transformation. Importantly, HPV 16/18 E6 and E7 oncoproteins can mediate expression of multiple target genes and proteins, such as p53/pRb, VEGF, HIF-$1{\alpha}$, cIAP-2, and hTERT, and contribute to cell proliferation, angiogenesis and cell immortalization through different signaling pathways in lung cancer. This article provides an overview of experiment data on HPV-associated lung cancer, describes the main targets on which HPV E6/E7 oncoproteins act, and further discusses the potential signaling pathways in which HPV E6/E7 oncoproteins are involved. In addition, we also raise questions regarding existing problems with the study of HPV-associated lung cancer.

20(S)-Protopanaxadiol enhances angiogenesis via HIF-1α-mediated VEGF secretion by activating p70S6 kinase and benefits wound healing in genetically diabetic mice

Er-Yun Zhang,Bo Gao,Hai-Lian Shi,Ling-Fang Huang,Li Yang,Xiao-Jun Wu,Zheng-Tao Wang 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

Impaired angiogenesis is one of the crucial factors that impede the wound healing process in diabetic foot ulcers (DFUs). In this study, we found that 20(S)-protopanaxadiol (PPD), an aglycone of ginsenosides in Panax notoginseng, stimulated angiogenesis and benefited wound healing in genetically diabetic mice. In HUVECs, PPD promoted cell proliferation, tube formation and VEGF secretion accompanied by increased nuclear translocalization of HIF-1α, which led to elevated VEGF mRNA expression. PPD activated both PI3K/Akt/mTOR and Raf/MEK/ERK signaling pathways in HUVECs, which were abrogated by LY294002 and PD98059. Furthermore, these two pathways had crosstalk through p70S6K, as LY294002, PD98059 and p70S6K siRNA abolished the angiogenic responses of PPD. In the excisional wound splinting model established in db/db diabetic mice, PPD (0.6, 6 and 60 mg ml− 1) accelerated wound closure, which was reflected by a significantly reduced wound area and epithelial gaps, as well as elevated VEGF expression and capillary formation. In addition, PPD activated PI3K/Akt/ERK signaling pathways, as well as enhanced p70S6K activity and HIF-1α synthesis in the wounds. Overall, our results revealed that PPD stimulated angiogenesis via HIF-1α-mediated VEGF expression by activating p70S6K through PI3K/Akt/mTOR and Raf/MEK/ERK signaling cascades, which suggests that the compound has potential use in wound healing therapy in patients suffering from DFUs.

Comparisons of Curative and Side Effects of Chemoradiotherapy among Xinjiang Han, Uigur and Kazakh Esophageal Carcinoma Patients

Zhang, Li,Ma, Li-Li,Zhang, Jian-Qing,Yang, Mei,Xun, Tu-Er,Li, Ai Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.1

Objective: This study aimed to explore the differences in the curative and side effects of chemoradiotherapy on esophageal cancer (EC) among Xinjiang Han, Uigur and Kazakh patients. Methods: 170 patients with IIA stage-IV of esophageal squamous cell carcinoma were analyzed retrospectively. Based on different nationalities, they were divided into the Han, Uigur and Kazakh groups. The 1-, 2- and 3-year survival rates, incidence of the side effects (including hematological toxicities, radioactive esophagitis and percutaneous reactions) and application of antibiotics and harmonics were compared among the groups. There was no significant difference in the short-term curative effects among the Han, Uigur and Kazakh groups. The 1- 2- and 3-year survival rates of the three groups were 84%, 40%, 26%; 78%, 27%, 18%; and 60%, 21%, 12% ($x^2$=14.497, P<0.05). The incidence rate of hamatological toxicity ${\geq}$Grade 2 in the Kazakh group was significantly lower than that in the Han or Uigur group. Results: The incidence rates of radioactive esophagitis and percutaneous reactions Grade 2 in the Han group were significantly higher than those in the Uigur or Kazakh group. There was no significant difference in the types of applied antibiotics among the groups, but there were significant differences in the days of antibiotic application and proportion of patients receiving harmonics between the Hans and either of other groups. Conclusion: Chemoradiotherapy shows a better effect in the long-term survival rate among Han EC patients compared with Uigur or Kazakh EC patients. Uigur and Kazakh patients show a better tolerance to the side effects of chemoradiotherapy compared with Hans.

Human Recombinant Endostatin Combined with Cisplatin Based Doublets in Treating Patients with Advanced NSCLC and Evaluation by CT Perfusion Imaging

Zhang, Feng-Lin,Gao, Er-Yun,Shu, Rong-Bao,Wang, Hui,Zhang, Yan,Sun, Peng,Li, Min,Tang, Wei,Jiang, Bang-Qin,Chen, Shuang-Qi,Cui, Fang-Bo Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Aims: To study the effectiveness of human recombinant endostatin injection (Endostar(R)) combined with cisplatin doublets in treating advanced non-small cell lung cancer (NSCLC), and to evaluate outcome by CT perfusion imaging. Methods: From April 2011 to September 2014, 76 patients with advanced NSCLC who were treated with platinum-based doublets were divided into group A (36 patients) and group B (40 patients). Endostar(R) 15mg/day was administered 4 days before chemotherapy and combined with chemotherapy from day 5 in group A, and combined with chemotherapy from the first day in Group B. Endostar(R) in the two groups was injected intravenously for 14 days. Results: Treatment effectiveness in the two groups differed with statistical significance (p<0.05). Effectiveness evaluated by CT perfusion imaging, BF, BV, MTT and PS also demonstrated significant differences (all p<0.05). Adverse reactions in the two groups did not significantly vary (p> 0.05). Conclusions: The response rate with Endostar(R) administered 4 days before chemotherapy and combined with chemotherapy from day 5 in group A was better than Endostar(R) combined with chemotherapy from the first day, and CT perfusion imaging could be a reasonable method for evaluation of patient outcomes.

The evaluation of online course of Traditional Chinese Medicine for Medical Bachelor, Bachelor of Surgery international students during the COVID-19 epidemic period

Zhang Qing,He Yi-Jing,Zhu Yu-Hang,Dai Min-Chen,Pan Man-Man,Wu Jia-Qi,Zhang Xian,Gu Ying-Er,Wang Fang-Fang,Xu Xiang-Rong,Qu Fan 한국한의학연구원 2020 Integrative Medicine Research Vol.9 No.3

Background: During the COVID-19 epidemic period, Traditional Chinese Medicine (TCM) course for international students of Medical Bachelor, Bachelor of Surgery (MBBS) program in Zhejiang University has shifted from traditional classroom to online environment. This study aimed to investigate MBBS international students’ perception on online TCM course, and to assess the online learning efficacy. Methods: A total of 84 MBBS international students attending course of “Basic Traditional Chinese Medicine” during 2020 academic years at Zhejiang University were enrolled in this study. A quantitative questionnaire was respectively completed before and after the TCM course using a pretest–post-test design. By means of two online learning platforms, Learning in ZJU and DingTalk, TCM course was broadcast in both live and archived format to students. Results: A total of 48 participants completed both baseline and follow-up questionnaires. The majority of participants preferred face-to-face classroom learning (26, 54.17% of total) when compared with online learning. Students felt that the course had brought in much benefits (mean 3.88, SD 0.87), and they were satisfied with the course content (mean 3.83, SD 0.95). Students’ TCM related knowledge and their behaviors of discussion and consulting were significantly improved by online TCM course (all P < 0.001). Students’ awareness of the necessity of TCM education and their feeling of difficulty in learning TCM were significantly strengthened (P = 0.042, 0.025, respectively). Conclusion: Online learning is a good alternative for TCM course of MBBS international students when classroom learning is suspended, whereas it cannot replace the need for onsite and face-to-face learning.

DEPTOR Expression Negatively Correlates with mTORC1 Activity and Tumor Progression in Colorectal Cancer

Lai, Er-Yong,Chen, Zhen-Guo,Zhou, Xuan,Fan, Xiao-Rong,Wang, Hua,Lai, Ping-Lin,Su, Yong-Chun,Zhang, Bai-Yu,Bai, Xiao-Chun,Li, Yun-Feng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

The mammalian target of rapamycin (mTOR) signaling pathway is upregulated in the pathogenesis of many cancers, including colorectal cancer (CRC). DEPTOR is an mTOR inhibitor whose expression is negatively regulated by mTOR. However, the role of DEPTOR in the development of CRC is not known. The aim of this study was to investigate the expression of DEPTOR and mTORC1 activity (P-S6) in a subset of CRC patients and determine their relation to tumor differentiation, invasion, nodal metastasis and disease-free survival. Here, Immunohistochemical expression of P-S6 (S235/236) and DEPTOR were evaluated in 1.5 mm tumor cores from 90 CRC patients and in 90 samples of adjacent normal mucosa by tissue microarray. The expression of P-S6 (S235/236) was upregulated in CRC, with the positive rate of P-S6 (S235/236) in CRC (63.3%) significantly higher than that in control tissues (36.7%, 30%) (p<0.05). P-S6 (S235/236) also correlated with high tumor histologic grade (p=0.002), and positive nodal metastasis (p=0.002). In contrast, the expression level of DEPTOR was correlated with low tumor histological grade (p=0.006), and negative nodal metastasis (p=0.001). Interestingly, P-S6 (S235/236) expression showed a significant negative association with the expression of DEPTOR in CRC (p=0.011, R= -0.279). However, upregulation of P-S6 (S235/236) (p=0.693) and downregulation of DEPTOR (p=0.331) in CRC were not significantly associated with overall survival. Thus, we conclude that expression of DEPTOR negatively correlates with mTORC1 activity and tumor progression in CRC. DEPTOR is a potential marker for prognostic evaluation and a target for the treatment of CRC.

Ethyl Methane Sulfonate Induces Disease Resistance in Begonia × hiemalis Fotsch.

Yang-Er Chen,Ying-Hong Zhang,Shu Yuan,Han-Mei Liu,Xian-Yin Zeng,Huai-Yu Zhang 한국원예학회 2014 Horticulture, Environment, and Biotechnology Vol.55 No.6

To evaluate the disease resistance of Begonia × hiemalis Fotsch. ‘Schwabenland Red’ mutants induced byethyl methane sulphonate (EMS), we investigated the incidence and severity of stem rot caused by Rhizoctoniasolani Kuhn, and their morphological changes. In this study, we obtained three mutants with highly resistant diseaseafter two rounds of screening when the inoculated amount was 3 sheets/plant. The severity scale was 0 and therewere no obvious symptoms of stem rot in highly resistant Begonia × hiemalis. However, most of EMS mutagenizedplants were susceptible to stem rot caused by R. solani under this inoculated amount. In addition, these resistantmutants had different phenotypes as compared with the uninfected control plants. The color of leaves of the R. solani-resistent mutants was different with the control plants and their leaves were bigger than that of the control. The shape and number of their flowers were obviously different, as compared to the control plants.