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      Protein expression profiles that underpin the preventive and therapeutic potential of Moringa oleifera Lam against azoxymethane and dextran sodium sulfate-induced mouse colon carcinogenesis

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          Abstract

          Previous studies in a mouse model have indicated the anticancer potential of boiled Moringa oleifera pod (bMO)-supplemented diets; however, its molecular mechanisms are still unclear. Therefore, the present study aimed to explore the protein expression profiles responsible for the suppressive effect of bMO supplementation on azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced mouse colon carcinogenesis. Analysis by gel electrophoresis and liquid chromatography-tandem mass spectrophotometry demonstrated that there were 125 proteins that were differentially expressed in mouse colon tissues between 14 experimental groups of mice. The differentially expressed proteins are involved in various biological processes, such as signal transduction, metabolism, transcription and translation. Venn diagram analysis of the differentially expressed proteins was performed in six selected mouse groups, including negative control, positive control mice induced by AOM/DSS, the AOM/DSS groups receiving preventive or therapeutic bMO diets and their bMO-supplemented control groups. This analysis identified 7 proteins; 60S acidic ribosomal protein P1 (Rplp1), fragile X mental retardation, cystatin 9, round spermatids protein, zinc finger protein 638, protein phosphatase 2C (Ppm1g) and unnamed protein product as being potentially associated with the preventive and therapeutic effects of bMO in AOM/DSS-induced mouse colon cancer. Analysis based on the search tool for interactions of chemicals (STITCH) database predicted that Rplp1 interacted with the apoptotic and inflammatory pathways, whereas Ppm1g was associated only with inflammatory networks. This proteomic analysis revealed candidate proteins that are responsible for the effects of bMO supplementation, potentially by regulating apoptotic and inflammatory signaling networks in colorectal cancer prevention and therapy.

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          Cultivation, Genetic, Ethnopharmacology, Phytochemistry and Pharmacology of Moringa oleifera Leaves: An Overview

          Moringa oleifera is an interesting plant for its use in bioactive compounds. In this manuscript, we review studies concerning the cultivation and production of moringa along with genetic diversity among different accessions and populations. Different methods of propagation, establishment and cultivation are discussed. Moringa oleifera shows diversity in many characters and extensive morphological variability, which may provide a resource for its improvement. Great genetic variability is present in the natural and cultivated accessions, but no collection of cultivated and wild accessions currently exists. A germplasm bank encompassing the genetic variability present in Moringa is needed to perform breeding programmes and develop elite varieties adapted to local conditions. Alimentary and medicinal uses of moringa are reviewed, alongside the production of biodiesel. Finally, being that the leaves are the most used part of the plant, their contents in terms of bioactive compounds and their pharmacological properties are discussed. Many studies conducted on cell lines and animals seem concordant in their support for these properties. However, there are still too few studies on humans to recommend Moringa leaves as medication in the prevention or treatment of diseases. Therefore, further studies on humans are recommended.
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            Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics.

            Fragile X syndrome (FXS) is the most frequent form of inherited intellectual disability and is also linked to other neurologic and psychiatric disorders. FXS is caused by a triplet expansion that inhibits expression of the FMR1 gene; the gene product, FMRP, regulates mRNA metabolism in the brain and thus controls the expression of key molecules involved in receptor signaling and spine morphology. While there is no definitive cure for FXS, the understanding of FMRP function has paved the way for rational treatment designs that could potentially reverse many of the neurobiological changes observed in FXS. Additionally, behavioral, pharmacological, and cognitive interventions can raise the quality of life for both patients and their families.
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              Establishment of a hepatocellular carcinoma cell line with unique metastatic characteristics through in vivo selection and screening for metastasis-related genes through cDNA microarray.

              To establish a hepatocellular carcinoma (HCC) cell line from lung metastatic lesions of human HCC in nude mice so as to provide a suitable model for the study of lung-metastasis-related molecular mechanisms. HCC clone cells MHCC97-H were inoculated into BALB/c nude mice, and the pulmonary metastatic lesions were harvested and re-implanted into nude mice for the second round of in vivo selection. The same procedure was repeated twice. A new cell line from the third round of lung metastases was established. A human HCC cell line with unique metastatic characteristics was established by in vivo selection. This cell line, designated as HCCLM3, was polygonal epithelial cell with hypotriploid karyotype and population doubling time of 34.9 h. The cells were positive for alpha fetoprotein (AFP), albumin, cytokeratin 8 (CK8), and negative for hepatitis B surface antigen (HBsAg) by immunocytochemistry. Fluorescence polymerase chain reaction (PCR) showed HBV DNA integration in the cellular genome. When 5 x 10(6) cells were injected subcutaneously into nude mice, tumorigenicity was 100%, with a latency period of 11+/-1 days. Five weeks after s.c. injection, the pulmonary metastatic rate was 100%, the median number of lung metastases being 121 per mouse. After orthotopic implantation of tumor tissue into nude mouse liver for 35 days, widespread loco-regional and distant metastases occurred, with 100% abdominal wall metastases, 80% intra-abdominal cavity metastases, 100% intrahepatic metastases, 70% diaphragm metastases, and 100% pulmonary metastases. The median number of lung metastatic lesions was 268 per mouse. Gene expression profile of HCCLM3 was compared by cDNA microarray with MHCC97-L, a clonal cell strain from the same parental cell line but with low metastatic potential; 25 differentially expressed genes were identified, 18 of which showed decreased expression and seven increased expression in HCCLM3, including the decreased expression of cell cycle control gene Rb2, mismatch repair gene hMSH2, and signal transduction gene protein kinase C beta2, and increased expression of signal transduction gene MAP kinase, kinase 6. A new HCC cell line characterized by high pulmonary metastases via s.c. and orthotopic inoculation was established, which provides a new model for the study of liver cancer metastasis. Its gene expression profile could help in the understanding of the mechanism of metastasis and provide potential targets for anti-metastasis intervention.
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                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                August 2020
                11 June 2020
                11 June 2020
                : 20
                : 2
                : 1792-1802
                Affiliations
                [1 ]Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170, Thailand
                [2 ]Funtional Ingredients and Food Innovation Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani 12120, Thailand
                [3 ]Section of Animal Laboratory, Research Division, National Cancer Institute, Bangkok 10400, Thailand
                [4 ]Food Cluster, Institute of Nutrition, Mahidol University, Nakhon Pathom 73170, Thailand
                [5 ]Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathumthani 12121, Thailand
                Author notes
                Correspondence to: Dr Chareeporn Akekawatchai, Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, 99 Moo 18, Piyachart Bldg, Paholyotin Road, Pathumthani 12121, Thailand, E-mail: cakekawatchai@ 123456gmail.com
                Dr Siriporn Tuntipopipat, Food Cluster, Institute of Nutrition, Mahidol University, Putthamonthon 4 Road, Putthamonthon, Nakhon Pathom 73170, Thailand, E-mail: siriporn.tun@ 123456mahidol.ac.th
                [*]

                Contributed equally

                Article
                OL-0-0-11730
                10.3892/ol.2020.11730
                7377166
                628ff28a-b0a0-4e69-993a-33869b516a3a
                Copyright: © Phannasil et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 05 October 2019
                : 01 April 2020
                Categories
                Articles

                Oncology & Radiotherapy
                aom/dextran-induced mouse colon carcinogenesis,mo,proteomics,gelc-ms/ms

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