Publications by authors named "Yingying Shao"

17 Publications

  • Page 1 of 1

Tumor microenvironment: a prospective target of natural alkaloids for cancer treatment.

Cancer Cell Int 2021 Jul 20;21(1):386. Epub 2021 Jul 20.

Tianjin State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.

Malignant tumor has become one of the major diseases that seriously endangers human health. Numerous studies have demonstrated that tumor microenvironment (TME) is closely associated with patient prognosis. Tumor growth and progression are strongly dependent on its surrounding tumor microenvironment, because the optimal conditions originated from stromal elements are required for cancer cell proliferation, invasion, metastasis and drug resistance. The tumor microenvironment is an environment rich in immune/inflammatory cells and accompanied by a continuous, gradient of hypoxia and pH. Overcoming immunosuppressive environment and boosting anti-tumor immunity may be the key to the prevention and treatment of cancer. Most traditional Chinese medicine have been proved to have good anti-tumor activity, and they have the advantages of better therapeutic effect and few side effects in the treatment of malignant tumors. An increasing number of studies are giving evidence that alkaloids extracted from traditional Chinese medicine possess a significant anticancer efficiency via regulating a variety of tumor-related genes, pathways and other mechanisms. This paper reviews the anti-tumor effect of alkaloids targeting tumor microenvironment, and further reveals its anti-tumor mechanism through the effects of alkaloids on different components in tumor microenvironment.
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http://dx.doi.org/10.1186/s12935-021-02085-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290600PMC
July 2021

The LncRNA RP11-279C4.1 Enhances the Malignant Behaviour of Glioma Cells and Glioma Stem-Like Cells by Regulating the miR-1273g-3p/CBX3 Axis.

Mol Neurobiol 2021 Jul 10;58(7):3362-3373. Epub 2021 Mar 10.

Department of Biochemistry and Molecular Biology, Medical School of Southeast University, # 87 Dingjiaqiao, Nanjing, 210009, China.

Glioma is the most common type of solid tumour affecting the central nervous system, and the survival rate of patients with glioma is low. However, the mechanism associated with glioma progression remains unclear. Growing evidence suggests that lncRNAs play essential roles in the initiation and progression of tumours, including gliomas. In the present study, we identified and verified the expression of the novel lncRNA RP11-279C4.1 by analyzing the TANRIC database and performing qRT-PCR assays, the results of which revealed its upregulation in glioma tissues and cell lines. The results of multiple functional experiments demonstrated that RP11-279C4.1 knockdown inhibited glioma malignant phenotypes, including cell proliferation, migration, invasion and cell self-renew ability in vitro. In addition, RP11-279C4.1 downregulation suppressed tumour growth in vivo. Mechanistically, RP11-279C4.1 induced CBX3 activation via competitively sponging miR-1273g-3p, and rescue assay results confirmed the importance of the RP11-279C4.1/miR-1273g-3p/CBX3 axis. Overall, the results of our present study demonstrated that RP11-279C4.1 functions as an oncogene that promotes tumour progression by modulating the miR-1273g-3p/CBX3 axis in glioma, suggesting that RP11-279C4.1 may be a novel therapeutic target for glioma.
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http://dx.doi.org/10.1007/s12035-021-02337-6DOI Listing
July 2021

Development and validation of a photographic atlas of food portions for accurate quantification of dietary intakes in China.

J Hum Nutr Diet 2021 Jun 6;34(3):604-615. Epub 2021 Jan 6.

Department of Maternal, Child and Adolescent Health, School of Public Health, Nanjing Medical University, Nanjing, China.

Background: Accurate estimation of food portion sizes remains an important challenge in dietary data collection. The present study aimed to develop a food atlas with adequate visual reference to improve the accuracy of dietary surveys in China.

Methods: A food atlas for dietary surveys in China was developed using three visual reference systems, namely, regularly placed food portions, the two-dimensional background coordinates and common objects known in daily life. The atlas was validated by estimating a meal before and after using the food atlas, and differences in weight estimation were compared using a paired t-test. In total, 50 college students participated in the study.

Results: After determination of food varieties; design of the food display; purchase, processing, cooking and weighing of food; photographing food; post-image processing and data processing, a total of 799 pictures of 303 types of food and two types of tableware were produced. The mean value of food weight estimated with the atlas was closer to the actual weight, and the variation range of these values was smaller and more stable than that estimated without the atlas. The differences estimated before and after using the atlas for all foods were significant (P < 0.05). Comparing the differences in weight before using the atlas, the error ranges of food samples were reduced.

Conclusions: A food atlas has been developed for a retrospective dietary survey in China, which can be used to enable a better understanding of nutritional adequacy in the Chinese population.
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http://dx.doi.org/10.1111/jhn.12844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246756PMC
June 2021

Anticancer activities of TCM and their active components against tumor metastasis.

Biomed Pharmacother 2021 Jan 11;133:111044. Epub 2020 Dec 11.

State Key Laboratory of Component-based Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China. Electronic address:

Traditional Chinese Medicine (TCM) has the characteristics of multiple targets, slight side effects and good therapeutic effects. Good anti-tumor effects are shown by Traditional Chinese Medicine prescription, Chinese patent medicine, single Traditional Chinese Medicine and Traditional Chinese medicine monomer compound. Clinically, TCM prolonged the survival time of patients and improved the life quality of patients, due to less side effects. Cancer metastasis is a complex process involving numerous steps, multiple genes and their products. During the process of tumor metastasis, firstly, cancer cell increases its proliferative capacity by reducing autophagy and apoptosis, and then the cancer cell capacity is stimulated by increasing the ability of tumors to absorb nutrients from the outside through angiogenesis. Both of the two steps can increase tumor migration and invasion. Finally, the purpose of tumor metastasis is achieved. By inhibiting autophagy and apoptosis of tumor cells, angiogenesis and EMT outside the tumor can inhibit the invasion and migration of cancer, and consequently achieve the purpose of inhibiting tumor metastasis. This review explores the research achievements of Traditional Chinese Medicine on breast cancer, lung cancer, hepatic carcinoma, colorectal cancer, gastric cancer and other cancer metastasis in the past five years, summarizes the development direction of TCM on cancer metastasis research in the past five years and makes a prospect for the future.
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http://dx.doi.org/10.1016/j.biopha.2020.111044DOI Listing
January 2021

Enhancing the Interface Contact of Stacking Perovskite Solar Cells with Hexamethylenediammonium Diiodide-Modified PEDOT:PSS as an Electrode.

ACS Appl Mater Interfaces 2020 Sep 2;12(37):42321-42327. Epub 2020 Sep 2.

State Key Laboratory of Fine Chemicals, School of Chemistry, Dalian University of Technology, Dalian 116024, China.

As an indispensable component of perovskite solar cells (PSCs), the commonly used Au and Ag electrodes still have some problems such as high cost and instability issues with regard to being corroded by iodide ions. In this paper, we report stacking perovskite solar cells (S-PSCs), which can avoid the use of precious metal electrodes and reduce the cost of devices and the requirements of equipment compared to conventional PSCs. The S-PSCs are composed of two semicells: a photoanode and a counter electrode (CE). For stacked devices, effective contact of the photoanode/CE interface is very important to the performance of the device. We used poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) as the electrode and modified it by hexamethylenediammonium diiodide (HDADI) to improve its physical and electrical properties. The surface of the HDADI-modified PEDOT:PSS becomes rough and achieves higher adhesion, which enables the photoanode and CE to be sufficiently connected. In addition, the energy-level structure of the HDADI-modified PEDOT:PSS matches better with that of the adjacent functional layers. Therefore, the S-PSCs performance has been significantly improved. Under an illumination area of 1 cm, the power-conversion efficiency (PCE) of the S-PSCs can reach 15.21%. Moreover, the S-PSCs can be disassembled and assembled flexibly and repeatedly disassembled 500 times with almost no change in the PCE. This has a positive impact on cell maintenance and modular production.
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http://dx.doi.org/10.1021/acsami.0c11247DOI Listing
September 2020

Sophoridine Inhibits Human Colorectal Cancer Progression via Targeting MAPKAPK2.

Mol Cancer Res 2019 12 1;17(12):2469-2479. Epub 2019 Oct 1.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

is a traditional Chinese medicine commonly used to treat cancer in China. However, its active components and underlying mechanism remain ambiguous. In this study, we have screened the pharmacokinetic parameters of the main chemical constituents of by Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform and have found that Sophoridine is one of the best antitumor active ingredients. We have found that MAPKAPK2 is a potential target for Sophoridine by the PharmMapper and KEGG databXase analysis. Moreover, we have found that Sophoridine selectively inactivates phospho-MAPKAPK2 (Thr222) and directly binds into the ATP site of MAPKAPK2 by molecular docking. Furthermore, we have found out a direct binding between MAPKAPK2 and Sophoridine by cellular thermal shift assay and drug affinity responsive targets stability assay. The inhibition effects are further confirmed by Western blot: Sophoridine significantly decreases phospho-MAPKAPK2 (Thr222) in a time-dependent manner, but there is no obvious change in its total expression in colorectal cancer cells. Clinical studies have shown that a higher level of MAPKAPK2 is associated with a poorer percent survival rate (prognosis). Furthermore, a higher level of MAPKAPK2 is positively associated with the enrichment of downregulation of apoptosis and autophagy by gene set enrichment analysis, as well as upregulation of proliferation and cell-cycle arrest. Taken together, our results suggest that the MAPKAPK2 plays a key role in Sophoridine-inhibited growth and invasion in colorectal cancers. IMPLICATIONS: These studies show that Sophoridine may be a promising therapeutic strategy that blocks tumorigenesis in colorectal cancers.
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http://dx.doi.org/10.1158/1541-7786.MCR-19-0553DOI Listing
December 2019

Malnutrition associated factors on children under 5 years old in Lhaviyani Atoll, Maldives.

J Biomed Res 2019 Mar;34(4):301-308

Department of Maternal, Child and Adolescent Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China.

In this report, we aimed to analyze the prevalence of undernutrition and associated factors among children under 5 years of age in Lhaviyani Atoll, Maldives. A total of 800 children (under 5 years old) and their mothers were selected for this study. Data was collected by using a pretested questionnaire and anthropometric measurements were taken from the hospital record book. Chi-square tests and multivariate logistic regression were used to find the association between nutritional status and determinants. The distribution of height for age and weight for age in surveyed children in Maldives was skewed to the left compared with the WHO standard. The prevalence of undernutrition based on underweight (10.75%), stunting (13.5%), and wasting (9.60%) was estimated to be 23.85% among children. Child age, gender and mother's education were significantly associated with undernutrition ( <0.05). Our survey highlighted that better nutritional interventions are needed to improve child health in this region.
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http://dx.doi.org/10.7555/JBR.33.20180141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386413PMC
March 2019

Lycorine Displays Potent Antitumor Efficacy in Colon Carcinoma by Targeting STAT3.

Front Pharmacol 2018 8;9:881. Epub 2018 Aug 8.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Signal transducer and activator of transcription 3 (STAT3) is an attractive therapeutic target for cancer treatment. In this study, we identify lycorine is an effective inhibitor of STAT3, leading to repression of multiple oncogenic processes in colon carcinoma. Lycorine selectively inactivates phospho-STAT3 (Tyr-705), and subsequent molecular docking uncovers that lycorine directly binds to the SH2 domain of STAT3. Consequently, we find that lycorine exhibits anti-proliferative activity and induces cell apoptosis on human colorectal cancer (CRC) . Lycorine induces the activation of the caspase-dependent mitochondrial apoptotic pathway, as indicated by activation of caspase and increase of the ratio of Bax/Bcl-2 and mitochondrial depolarization. Overexpressing STAT3 greatly blocks these effects by lycorine in CRC cells. Finally, lycorine exhibits a potential therapeutic effect in xenograft colorectal tumors by targeting STAT3 without observed toxicity. Taken together, the present study indicates that lycorine acts as a promising inhibitor of STAT3, which blocks tumorigenesis in colon carcinoma.
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http://dx.doi.org/10.3389/fphar.2018.00881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092588PMC
August 2018

Magnolin promotes autophagy and cell cycle arrest via blocking LIF/Stat3/Mcl-1 axis in human colorectal cancers.

Cell Death Dis 2018 06 13;9(6):702. Epub 2018 Jun 13.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.

Magnolin is a multi-bioactive natural compound that possesses underlying anti-cancer properties. However, the mechanisms underlying remain to be elucidated. Here, we report the role of magnolin in suppressing human colorectal cancer (CRC) cells via activating autophagy and cell cycle arrest in vitro and in vivo. Pre-treatment of cells with specific autophagy inhibitor (3-methyladenine) or knockdown of endogenous LC-3B by siRNA significantly abrogates magnolin-induced cell cycle arrest. Molecular validation mechanistically shows that magnolin-induced autophagy and cell cycle arrest in CRC cells is correlated with decreased transcriptional levels of leukemia inhibitory factor (LIF), and we further find that inhibition of LIF decreases phosphorylation level of Stat3 and represses transcriptional expression of Mcl-1. Furthermore, magnolin-induced autophagy and cell cycle arrest suppress the growth of xenograft colorectal tumors without apparent toxicity. Finally, we evaluate the clinical correlation of LIF/Stat3/Mcl-1 in CRC patient tissues. As expected, LIF, p-Stat3, and Mcl-1 levels are high in CRC tissue but are scarcely found in normal colon tissue. High positive expressions of LIF or Mcl-1 are associated with poor prognosis. Doubly positive cases have shown the worst outcome. Taken together, our results have clarified a novel molecular mechanism whereby magnolin induces autophagy and cell cycle arrest through LIF/Stat3/Mcl-1 pathway in CRCs. Our results also have revealed that magnolin has a promising therapeutic potential in CRCs.
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http://dx.doi.org/10.1038/s41419-018-0660-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999973PMC
June 2018

Preparation of wheat straw-supported Nanoscale Zero-Valent Iron and its removal performance on ciprofloxacin.

Ecotoxicol Environ Saf 2018 Aug 24;158:100-107. Epub 2018 Apr 24.

Shandong Provincial Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science and Engineering, Shandong University, Jinan 250100, China.

Wheat straw-supported Nanoscale Zero-Valent Iron particles (WS-NZVI) were successfully synthesized, which were used for Ciprofloxacin hydrochloride (CIP) removal in simulation wastewater. The structure, chemical composition and micro-morphology of WS-NZVI and Nanoscale Zero-Valent Iron (NZVI) were characterized by scanning electron microscopy analysis (SEM), X-ray diffraction (XRD), as well as the Fourier Transformed IR spectra (FT-IR). XRD results proved the existence of Fe°, and SEM images indicated that the agglomeration of NZVI was effectively inhibited when loaded on wheat straw. Besides, the effects of initial solution pH, CIP concentration, adsorbents dosage and contacting time on the removal efficiency of CIP by WS-NZVI and NZVI were investigated. The experimental results showed that, compared with NZVI and wheat straw, WS-NZVI possessed higher removal efficiency for CIP, and the maximum removal capacity of CIP by WS-NZVI was 363.63 mg g (25 °C). Furthermore, WS-NZVI was suitable for wider pH range (pH = 4-10) in comparison with NZVI. For the WS-NZVI, the kinetic was better fitted with pseudo-second-order equation, rather than pseudo-first-order equation. The Mass spectrometry (MS) analysis deduced that the degradation reaction mainly occurred on quinolone groups piperazinyl ring. Therefore, it is feasible that using wheat straw as a support material to enhance the performance of NZVI, and the synthesized WS-NZVI has a potential in the organic compounds elimination because of its redox reaction activity.
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http://dx.doi.org/10.1016/j.ecoenv.2018.04.020DOI Listing
August 2018

Highly Enhanced Photoreductive Degradation of Polybromodiphenyl Ethers with g-C3N4/TiO2 under Visible Light Irradiation.

Nanomaterials (Basel) 2017 Apr 3;7(4). Epub 2017 Apr 3.

Department of Chemistry, Shaoxing University, Shaoxing 312000, Zhejiang, China.

A series of high activity photocatalysts g-C3N4-TiO2 were synthesized by simple one-pot thermal transformation method and characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy, Brunauer-Emmett-Teller (BET) surface area, and ultraviolet-visible diffuse reflectance spectroscopy (UV-Vis-DRS). The g-C3N4-TiO2 samples show highly improved photoreductive capability for the degradation of polybromodiphenyl ethers compared with g-C3N4 under visible light irradiation. Among all the hybrids, 0.02-C3N4-TiO2 with 2 wt % g-C3N4 loaded shows the highest reaction rate, which is 15 times as high as that in bare g-C3N4. The well-matched band gaps in heterojunction g-C3N4-TiO2 not only strengthen the absorption intensity, but also show more effective charge carrier separation, which results in the highly enhanced photoreductive performance under visible light irradiation. The trapping experiments show that holetrapping agents largely affect the reaction rate. The rate of electron accumulation in the conductive band is the rate-determining step in the degradation reaction. A possible photoreductive mechanism has been proposed.
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http://dx.doi.org/10.3390/nano7040076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408168PMC
April 2017

[Validation of an online dietary assessment tool].

Wei Sheng Yan Jiu 2017 Mar;46(2):272-276

Department of Maternal, Child and Adolescent Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China.

Objective: To assess the validity of eat-right assistant( ERA) as an online dietary assessment tool.

Methods: Women employees in child-bearing age in a company in Shanghai and pregnant women who received regular antenatal care, lactating women whose children had physical examination in a village hospital in Suzhou were recruited into this study. They recorded their food and drink intakes on the ERA and completed 24-hour dietary recalls for three days consecutively. The energy, nutrient and food group intakes of the two methods were calculated for further comparisons.

Results: A total of ninety participants completed the study. Except for fruit intake, no significant differences were found between the two methods for mean intakes of energy and nutrients as well as other food intakes. Correlation coefficients ranged from 0. 61- 0. 93( mean0. 75). Bland-Altman plots showed agreement between the two methods.

Conclusion: ERA is a relatively reliable tool for dietary assessment and is potential to be applied in target population.
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March 2017

MiR-135a and MRP1 play pivotal roles in the selective lethality of phenethyl isothiocyanate to malignant glioma cells.

Am J Cancer Res 2016 1;6(5):957-72. Epub 2016 May 1.

Department of Clinical Pharmacology, Xiangya Hospital, Central South UniversityChangsha 410008, P. R. China; Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of PharmacogeneticsChangsha 410078, P. R. China.

Amounting evidence has demonstrated that phenethyl isothiocyanate (PEITC) is a strong inducer of reactive oxygen species (ROS) and functions as a selective killer to various human cancer cells. However, it remains obscure whether PEITC has potential selective lethality to malignant glioma cells. Thus in this study, we performed multiple analysis such as MTT assay, Hoechst 33258 staining, flow cytometry, foci formation, RT-PCR, Western blot, and transfection to explore the selective lethality of PEITC to malignant glioma cells and the underlying mechanisms. We found that PEITC induced a selective apoptosis and suppressed tumorigenicity and migration of malignant glioma cells. Furthermore, we found PEITC significantly induced GSH depletion, ROS production, caspase-9 and caspase-3 activation, and miR-135a upregulation in malignant glioma cells but not in normal cells. Moreover, PEITC activated the miR-135a-mitochondria dependent apoptosis pathway as demonstrated by downregulation of STAT6, SMAD5 and Bcl-xl while upregulation of Bax expression and Cytochrome-C release in malignant glioma cell lines but not in the immortalized human normal glial HEB cells. Correspondingly, the above PEITC-induced activation of the ROS-MiR-135a-Mitochondria dependent apoptosis pathways in malignant glioma was attenuated by pre-transfection with miR-135a inhibitor, pre-treatment with multidrug resistance-associated protein 1 (MRP1) inhibitor Sch B, or combination with glutathione (GSH). These results revealed that PEITC selectively induced apoptosis of malignant glioma cells through MRP1-mediated export of GSH to activate ROS-MiR-135a-Mitochondria dependent apoptosis pathway, suggesting a potential application of PEITC for treating glioma.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4889712PMC
June 2016

One-pot approach to 1,2-disubstituted indoles via Cu(II)-catalyzed coupling/cyclization under aerobic conditions and its application for the synthesis of polycyclic indoles.

J Org Chem 2014 Oct 22;79(19):9000-8. Epub 2014 Sep 22.

Department of Chemistry, College of Chemistry and Life Sciences, Zhejiang Normal University , Jinhua 321004, People's Republic of China.

A straightforward assembly of 1,2-disubstituted indoles has been developed through a Cu(II)-catalyzed domino coupling/cyclization process. Under aerobic conditions, a wide range of 1,2-disubstituted indole derivatives were efficiently and facilely synthesized from 2-alkynylanilines and boronic acids. 2-(2-Bromoaryl)-1-aryl-1H-indoles, which were selectively generated in one pot under the Cu catalysis, afforded the indolo[1,2-f]phenanthridines via Pd-catalyzed intramolecular direct C(sp(2))-H arylation. The one-pot tandem approaches to the polycyclic indole derivatives were also successfully achieved.
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http://dx.doi.org/10.1021/jo501250uDOI Listing
October 2014

[Protective effect of purple sweet potato flavonoids on CCL4-induced acute liver injury in mice].

Zhejiang Da Xue Xue Bao Yi Xue Ban 2013 Nov;42(6):649-53

Zhejiang University City College, School of Medicine, Hangzhou 310015, China.

Objective: To investigate the protective effect of purple sweet potato flavonoids (PSPF) on CCl4-induced acute liver injury in mice.

Methods: Sixty mice were randomly divided into six groups (n=10 in each): blank group, model group, PSPF groups (400 mg*kg(-1), 200 mg*kg-1 and 100 mg*kg(-1)) and positive control group (DDB 150 mg*kg(-1)). Acute liver injury was induced by administration of peanut oil with 0.1% CCl4 (10 mg*kg(-1)) in mice. The viscera index, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were measured, and the activities of superoxide dismutase (SOD) and the contents of malondialdehyde (MDA) in hepatic tissues were also measured. The pathological changes of liver were observed with microscopy.

Results: PSPF significantly decreased serum ALT, AST and LDH levels (P<0.05 or P<0.01) and MDA content in hepatic tissues (P<0.01), increased the activities of SOD (P<0.01).

Conclusion: Purple sweet potato total flavonoids can prevent CCl4-induced acute liver injury in mice, which may be related to inhibition of lipid peroxidation and reduction of oxygen free radicals.
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November 2013

Melatonin reduces bacterial translocation by preventing damage to the intestinal mucosa in an experimental severe acute pancreatitis rat model.

Exp Ther Med 2013 Dec 10;6(6):1343-1349. Epub 2013 Oct 10.

Department of Gastroenterology and Hepatology, First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China.

Recent studies have demonstrated that melatonin significantly decreased all studied acute pancreatitis-associated inflammatory parameters, in addition to reducing apoptosis and necrosis associated with pancreatic injury. However, the effect of melatonin on gut barrier dysfunction and bacterial translocation has not been fully elucidated. This study aimed to investigate the protective effects of melatonin on intestinal integrity in a rat model of severe acute pancreatitis (SAP) to evaluate whether melatonin prevented intestine barrier dysfunction and reduced bacterial translocation. Forty male Sprague Dawley (SD) rats were randomly divided into three groups, with 8 rats in the sham operation (SO) group, 18 rats in the SAP group and 14 SAP rats in the melatonin treatment (MT) group. SAP was induced by retrograde injection of 4% taurocholate into the biliopancreatic duct. Melatonin was administered 30 min prior to taurocholate injection in the melatonin-treated rats. All rats were sacrificed 24 h subsequent to pancreatitis induction. Real-time fluorescence quantitative polymerase chain reaction was used to detect and quantify () O157 in postcava blood. The microvilli structure was also analyzed with transmission electron microscopy. The level of DNA in the MT group was significantly lower than in rats in the SAP group. No DNA was detected in the control group. Villus height and crypt depth in the ileum were significantly higher in the MT and control groups compared to the SAP group, and were significantly higher in the MT group than in the SAP group. These results suggested that melatonin prevented gut barrier dysfunction and reduced bacterial translocation, resulting in reduced pancreatic-associated infections and decreased early mortality rates.
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http://dx.doi.org/10.3892/etm.2013.1338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829749PMC
December 2013

Melatonin ameliorates acute necrotizing pancreatitis by the regulation of cytosolic Ca2+ homeostasis.

Pancreatology 2012 May-Jun;12(3):257-63. Epub 2012 Feb 15.

Department of Gastroenterology and Hepatology, First Affiliated Hospital of Wenzhou Medical College, Wenzhou, 325000 Zhejiang, China.

Objectives: This study aims to investigate the relationship between the protective effects of melatonin in pancreas and the expression of sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) and Na(+)/Ca(2+) exchanger (NCX) in rats with acute necrotizing pancreatitis (ANP), to verify whether melatonin ameliorates ANP by alleviating calcium overload.

Methods: Ninety-six male Sprague-Dawley rats were randomly divided into four groups (sham operation group, ANP group, melatonin treatment group, melatonin contrast group). ANP was induced by the retrograde injection of 4% taurocholate (1 ml/kg body weight) into the biliopancreatic duct. Melatonin (50 mg/kg body weight) was administered 30 min before the induction of ANP in the melatonin treatment group. Rats in each group were euthanized at 1, 4, and 8 h after ANP induction. Pancreatic tissues were removed to measure SERCA and NCX levels and cytosolic calcium ion (Ca(2+)) concentration ([Ca(2+)](i)).

Results: At each time point, SERCA and NCX levels in the melatonin treatment group were significantly higher than that in the ANP group, and lower than that in the sham group and the melatonin contrast group. These levels did not differ between the 4- and 8-h time points in the ANP group. [Ca(2+)](i) in pancreatic acinar cells was higher in the melatonin treatment group than in the sham group and the melatonin contrast group, but lower than in the ANP group, at each time point.

Conclusion: Melatonin can reduce pancreatic damage via the up-regulation of SERCA and NCX expression, which can alleviate calcium overload in pancreatic acinar cells.
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http://dx.doi.org/10.1016/j.pan.2012.02.004DOI Listing
November 2012
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