ABSTRACT
Cholesterol-25-hydroxylase (CH25H) and its enzymatic product 25-hydroxycholesterol (25HC) exert broadly antiviral activity including inhibiting HIV-1 infection. However, their antiviral immunity and therapeutic efficacy in a nonhuman primate model are unknown. Here, we report that the regimen of 25HC combined with antiretroviral therapy (ART), provides profound immunological modulation towards inhibiting viral replication in chronically SIVmac239-infected rhesus macaques (RMs). Compared to the ART alone, this regimen more effectively controlled SIV replication, enhanced SIV-specific cellular immune responses, restored the ratio of CD4/CD8 cells, reversed the hyperactivation state of CD4+ T cells, and inhibited the secretion of proinflammatory cytokines by CD4+ and CD8+ T lymphocytes in chronically SIV-infected RMs. Furthermore, the in vivo safety and the preliminary pharmacokinetics of the 25HC compound were assessed in this RM model. Taken together, these assessments help explain the profound relationship between cholesterol metabolism, immune modulation, and antiviral activities by 25HC. These results provide insight for developing novel therapeutic drug candidates against HIV-1 infection and other related diseases.
Subject(s)
HIV Infections , Simian Acquired Immunodeficiency Syndrome , Simian Immunodeficiency Virus , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , CD4-Positive T-Lymphocytes , HIV Infections/drug therapy , Hydroxycholesterols , Macaca mulatta , Simian Acquired Immunodeficiency Syndrome/drug therapyABSTRACT
OBJECTIVE: To observe the efficacy and safety of the goebell-stoeckel fascia lata sling operation for female stress urinary incontinence. METHODS: Thirteen patients suffering from stress urinary incontinence (SUI) with prolapsed vagina were enrolled into this study. The average follow-up time was thirty months. The outcomes and complications after operation were analysed. RESULTS: All patients had complete cure. There were no vaginal bleeding, infection, rejection for surgery and no recurrent cases. Five patients had mild temporary dysuria, which disappeared within one month. CONCLUSION: The goebell-stoeckel fascia lata sling operation is an effective, safe, well-tolerated procedure for treatment of SUI.
