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The effect of TFmix on the amyloid fibril formation of semen-derived enhancer of virus infection (SEVI) peptide was detected by transmission electron microscopy. The toxicity of the TFmix gel was evaluated using human vaginal and cervical epithelial cell lines and rabbit vaginal irritation models, respectively. Levels of proinflammatory cytokines (IL-1\u03b2, IL-6, IL-8, and TNF-\u03b1) and immunoregulatory cytokines (IL-10 and GM-CSF) in cervicovaginal lavages (CVLs) were measured by ELISA kits. Proliferating cell nuclear antigen (PCNA) immunostaining was performed to evaluate inflammation in the vaginal tissues. TFmix gel could degrade SEVI-specific amyloid fibrils and showed low cytotoxicity to epithelial cells of the female reproductive tract. No apparent cervicovaginal toxicity was observed at any time point evaluated following the intravaginal administration of TFmix gel to rabbits, whereas application of N-9 gel resulted in damage to the vaginal epithelium. Neither proinflammatory nor immunoregulatory cytokine production was triggered by TFmix gel. Only low expression of PCNA was observed in vaginal tissues of TFmix gel-treated rabbits. The concentration of TFmix in plasma was very low (below the lower limit of quantitation) 1\u2009h after a single vaginal administration of TFmix gel. However, TFmix was still detected in the cervicovaginal lavages (CVLs) 6\u2009h after treatment, indicating that it could be retained in the vaginal cavity for a long period of time. With its potent anti-HIV-1 activity, marked stability at acidic condition, low mucosal toxicity, and lack of systemic absorption, TFmix gel can be considered as an inexpensive and safe microbicide candidate for the prevention of HIV sexual transmission.<\/jats:p>","DOI":"10.1089\/aid.2012.0084","type":"journal-article","created":{"date-parts":[[2012,8,6]],"date-time":"2012-08-06T23:50:22Z","timestamp":1344297022000},"page":"1498-1508","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":14,"title":["Vaginal Gel Formulation Based on Theaflavin Derivatives As a Microbicide to Prevent HIV Sexual Transmission"],"prefix":"10.1177","volume":"28","author":[{"given":"Jie","family":"Yang","sequence":"first","affiliation":[{"name":"Southern Medical University","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Li","sequence":"additional","affiliation":[{"name":"Southern Medical University","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Jin","sequence":"additional","affiliation":[{"name":"Southern Medical University","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suiyi","family":"Tan","sequence":"additional","affiliation":[{"name":"Southern Medical University","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayin","family":"Qiu","sequence":"additional","affiliation":[{"name":"Southern Medical University","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Yang","sequence":"additional","affiliation":[{"name":"Southern Medical University","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanqing","family":"Ding","sequence":"additional","affiliation":[{"name":"Southern Medical University","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Hong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Southern Medical University","place":["China"]},{"name":"Macau University of Science and Technology","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shibo","family":"Jiang","sequence":"additional","affiliation":[{"name":"Southern Medical University","place":["China"]},{"name":"Fudan University","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuwen","family":"Liu","sequence":"additional","affiliation":[{"name":"Southern Medical University","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2012,11,1]]},"reference":[{"key":"e_1_3_3_2_2","unstructured":"WHO. 2011progress report on the global AIDS epidemichttp:\/\/www.who.int\/hiv\/pub\/progress_report2011\/en\/."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1258\/095646203762869160"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1080\/02648725.2004.10648050"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69131-9"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.2174\/157016209788347921"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001432-200202000-00010"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1193748"},{"key":"e_1_3_3_9_2","first-page":"85","article-title":"Safety of multiple daily applications of COL-1492, a nonoxynol-9 vaginal gel, among female sex workers","volume":"14","author":"Van DL","year":"2000","unstructured":"Van DL, , Chandeying V, , Ramjee G et al. 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