Echinacoside and Cistanche tubulosa(Schenk) R. wight have male reproductive protection effect by targeting hypothalamic and rogen receptor

OBJECTIVE Cistanche deserticola Y.C.Ma is an official plant that grows in arid or semi-arid areas.Our early work demonstrated that Cistanche extracts protect against sperm damage in mice under bisphenol A induced reproductive damage.Echinacoside(ECH) is one of the major active components.The present study investigated the mechanisms behind the possible protective effects of ECH against oligoasthenospermia in rat and identified the interaction between ECH and AR.METH.ODS The distribution of ECH was assayed by HPLC,the quantity and quality of sperm was evaluated and hormone levels were determined by radioimmunosorbent assay.The levels of androgen receptor(AR) and key steroidogenic-related genes were reduced as determined by Western blotting and qPCR analysis.The interaction between ECH and AR were evaluated by fluorescence localization assay,indirect ELISA and molecular docking.RESULTS ECH significantly increased the quantity of sperm and secretions of luteinizing hormone and testosterone.ECH was distributed to the hypothalamus but not in the testes.ECH combined with hypothalamic AR in the pocket of Met-894 and Val-713 to inhibit transfer of AR from the cytoplasm to nuclei in the hypothalamus.While negative feedback of sex hormone regula.tion was inhibited,positive feedback was stimulated to increase the secretion of luteinizing hormone and testosterone subsequently enhancing the quantity of sperm.C.militaris significantly alleviated the BPA-induced reproductive damage by increasing testicular superoxide dismutase(SOD),glutathione peroxidase(GSH-PX) and glutathione(GSH);as well as by reducing serum malondialdehyde(MDA).C.militaris not only obviously enhanced the levels of serumLH and T,but it also improved the sperm count and motility compared to the BPA-treated group.CONCLUSION C.militaris and ECH protect the BPA induced reproductive damage.ECH blocks AR activity in the hypothalamus to increase the quantity of sperm and protect against oligoasthenospermia in rats.

Human Leukocyte Antigen-A Allele Distribution in Nasopharyngeal Carcinoma Patients Showing Anti-Melanoma-Associated Antigen A or Synovial Sarcoma X-2 T Cell Response in Blood

Background： Development of innovative immunotherapy is imperative to improve the poor survival of the nasopharyngeal carcinoma （NPC） patients. In this study, we evaluated the T cell response to melanoma-associated antigen （MAGE）-A1, MAGE-A3, or synovial sarcoma X-2 （SSX-2） in the peripheral blood of treatment-naive NPC patients. The relationship of responses among the three proteins and the human leukocyte antigen （HLA）-A types were analyzed to provide evidence of designing novel therapy. Methods： Sixty-one NPC patients admitted into the Tumor Hospital affiliated to the Xinjiang Medical University between March 2015 and July 2016 were enrolled. Mononuclear cells were isolated from the peripheral blood before any treatment. HLA-A alleles were typed with Sanger sequence-based typing technique. The T cell response to the MAGE-A1, MAGE-A3, or SSX-2 was evaluated with the Enzyme-Linked ImmunoSpot assay. Mann-Whitney U-test was used to compare the T cell responses from different groups. Spearman＇s rank correlation was used to analyze the relationship of T cell responses. Results： HLA-A＊02：01, A＊02：07, and A＊24：02 were the three most frequent alleles （18.9%, 12.3%, and 11.5%, respectively） among the 22 detected alleles. 31.1%, 19.7%, and 16.4% of the patients displayed MAGE-A1, MAGE-A3, or SSX-2-specific T cell response, respectively. The magnitudes of response to the three proteins were 32.5, 38.0, and 28.7 SFC/106 peripheral blood mononuclear cells, respectively. The T cell response against the three proteins correlated with each other to different extent. The percentage of A＊02：01 and A＊24：02 carriers were significantly higher in patients responding to any of the three proteins compared to the nonresponders. Conclusion： MAGE-A1, MAGE-A3, or SSX-2-specific T cell responses were detectable in a subgroup of NPC patients, the frequency and magnitude of which were correlated.