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GAS5 was able to bind to miR-144 and regulate the expressin of mTOR. mTOR inhibitor GDC-0349 could reverse the inhibition of GAS5 on autophagy but could not reverse its effect on apoptosis.<br /><br /> GAS5 expresses highly in OA cartilage tissues and increases with the progression of OA. GAS5 inhibits autophagy and promotes the apoptosis of OACs, and the inhibition of autophagy may be related to its regulation of mTOR.<br /><br />GAS5 expresses highly in OA cartilage tissues and increases with the progression of OA. GAS5 inhibits autophagy and promotes the apoptosis of OACs, and the inhibition of autophagy may be related to its regulation of mTOR.<br /><br /> Does fertility treatment (FT) significantly increase the incidence of breast, ovarian, endometrial or cervical cancer?<br /><br /> Overall, FT does not significantly increase the incidence of breast, ovarian or endometrial cancer and may even reduce the incidence of cervical cancer.<br /><br /> Infertility affects more than 14% of couples. [https://www.selleckchem.com/products/ipa-3.html selleck kinase inhibitor] Infertility and nulliparity are established risk factors for endometrial, ovarian and breast cancer, yet the association with FT is more contentious.<br /><br /> A literature search was carried out using Cochrane Library, EMBASE, Medline and Google Scholar up to December 2019. Peer-reviewed studies stating cancer incidence (breast, ovarian, endometrial or cervical) in FT and no-FT groups were identified. Out of 128 studies identified, 29 retrospective studies fulfilled the criteria and were included (n = 21 070 337).<br /><br /> In the final meta-analysis, 29 studies were included breast (n = 19), ovarian (n = 19), endometrial (n = 15) and cervical (n = 13), 17 studies involved multiple cancer types and so weree with previously published meta-analyses for individual cancers but the association between IVF and CC treatment and an increase in ovarian cancer incidence requires additional work to understand the potential mechanism driving this association. In particular, focusing on (i) discriminating specific treatments effects from an inherent risk of malignancy; (ii) differential risk profiles among specific patient sub-groups (refractory treatment and obesity); and (iii) understanding the impact of FT outcomes on cancer incidence.<br /><br /> This study did not receive any funding. The authors have no financial, personal, intellectual and professional conflicts of interest to declare.<br /><br /> CRD42019153404.<br /><br />CRD42019153404.Antiretroviral therapy effectively controls human immunodeficiency virus (HIV) infection. However, a reservoir of latently infected cells persists under suppressive therapy, constituting a major barrier to an HIV cure. The block-and-lock approach to a functional cure aims at the transcriptional and epigenetic silencing of proviruses, blocking viral reactivation in the absence of therapy, preventing disease progression and transmission, despite the presence of detectable integrated proviruses. This approach has been put forward for exploration based on the activity of didehydro-cortistatin A, an inhibitor of the HIV transcriptional activator Tat. Here we review the mechanisms by which didehydro-cortistatin A inhibition of Tat's feedback loop transcriptional amplification results in epigenetic silencing of the HIV promoter, and we discuss the benefits and limitations of the block-and-lock approach for an HIV cure.The latent reservoir for human immunodeficiency virus type 1 (HIV-1) in resting CD4+ T cells is a major barrier to cure. The dimensions of the reservoir problem can be defined with 2 assays. A definitive minimal estimate of the frequency of latently infected cells is provided by the quantitative viral outgrowth assay (QVOA), which detects cells that can be induced by T-cell activation to release infectious virus. In contrast, the intact proviral DNA assay (IPDA) detects all genetically intact proviruses and provides a more accurate upper limit on reservoir size than standard single-amplicon polymerase chain reaction assays which mainly detect defective proviruses. The frequency of cells capable of initiating viral rebound on interruption of antiretroviral therapy lies between the values produced by the QVOA and the IPDA. We argue here that the 1-2-log difference between QVOA and IPDA values in part reflects that the fact that many replication-competent proviruses are not readily induced by T-cell activation. Findings of earlier studies suggest that latently infected cells can be activated to proliferate in vivo without expressing viral genes. The proliferating cells nevertheless retain the ability to produce virus on subsequent stimulation. The low inducibility of latent proviruses is a major problem for the shock-and-kill strategy for curing HIV-1 infection, which uses latency-reversing agents to induce viral gene expression and render infected cells susceptible to immune clearance. The latency-reversing agents developed to date are much less effective at reversing latency than T-cell activation. Taken together, these results indicate that HIV-1 eradication will require the discovery of much more effective ways to induce viral gene expression.Since the first case of an HIV sterilizing cure was published, remarkable progress has been made in our understanding of the mechanisms behind HIV persistence. However, our goal of achieving a safe and broadly-available treatment for sustained HIV remission has proven elusive. In this supplement, we provide a series of articles reviewing the technical hurdles facing the field, key assays to measure HIV persistence and the next-generation of therapeutics for HIV remission.Antiretroviral therapy effectively controls human immunodeficiency virus (HIV) replication but it is unable to fully eradicate the HIV reservoir and treatment must be life-long. Progress toward a strategy for HIV remission will require overcoming key hurdles to fill gaps in our understanding of HIV persistence, but the identification of individuals who have attained sterilizing or functional HIV cure show that such a goal is achievable. In this review, we first outline challenges in targeting the HIV reservoir, including difficulties identifying HIV-infected cells, ongoing work elucidating the complex intracellular environment that contribute to HIV latency, and barriers to reactivating and clearing the HIV reservoir. We then review reported cases of HIV sterilizing cure and explore natural models of HIV remission and the promise that such HIV spontaneous and posttreatment controllers may hold in our search for a broadly-applicable strategy for the millions of patients living with HIV.