Low back pain(LBP)is the world's leading cause of disability and is increasing in prevalence more rapidly than any other pain condition.Intervertebral disc(IVD)degeneration and facet joint osteoarthritis(FJOA)are ...Low back pain(LBP)is the world's leading cause of disability and is increasing in prevalence more rapidly than any other pain condition.Intervertebral disc(IVD)degeneration and facet joint osteoarthritis(FJOA)are two common causes of LBP,and both occur more frequently in elderly women than in other populations.Moreover,osteoarthritis(OA)and OA pain,regardless of the joint,are experienced by up to twice as many women as men,and this difference is amplified during menopause.Changes in estrogen may be an important contributor to these pain states.Receptors for estrogen have been found within IVD tissue and nearby joints,highlighting the potential roles of estrogen within and surrounding the IVDs and joints.In addition,estrogen supplementation has been shown to be effective at ameliorating IVD degeneration and OA progression,indicating its potential use as a therapeutic agent for people with LBP and OA pain.This review comprehensively examines the relationship between estrogen and these pain conditions by summarizing recent preclinical and clinical findings.The potential molecular mechanisms by which estrogen may relieve LBP associated with IVD degeneration and FJOA and OA pain are discussed.展开更多
Nullbasic is a mutant form of HIV-1 Tat that has strong ability to protect cells from HIV-1 replication by inhibiting three different steps of viral replication: reverse transcription, Rev export of viral m RNA from t...Nullbasic is a mutant form of HIV-1 Tat that has strong ability to protect cells from HIV-1 replication by inhibiting three different steps of viral replication: reverse transcription, Rev export of viral m RNA from the nucleus to the cytoplasm and transcription of viral m RNA by RNA polymerase II. We previously showed that Nullbasic inhibits transduction of human cells including T cells by HIV-1-based lentiviral vectors. Here we investigated whether the Nullbasic antagonists huTat2(a Tat targeting intrabody), HIV-1 Tat or Rev proteins or cellular DDX1 protein could improve transduction by a HIV-1 lentiviral vector conveying Nullbasic-Zs Green1 to human T cells. We show that overexpression of huTat2, Tat-FLAG and DDX1-HA in virus-like particle(VLP) producer cells significantly improved transduction efficiency of VLPs that convey Nullbasic in Jurkat cells. Specifically, co-expression of Tat-FLAG and DDX1-HA in the VLP producer cell improved transduction efficiency better than if used individually. Transduction efficiencies could be further improved by including a spinoculation step. However, the same optimised protocol and using the same VLPs failed to transduce primary human CD4^+T cells. The results imply that the effects of Nullbasic on VLPs on early HIV-1 replication are robust in human CD4^+T cells. Given this significant block to lentiviral vector transduction by Nullbasic in primary CD4^+T cells, our data indicate that gammaretroviral, but not lentiviral, vectors are suitable for delivering Nullbasic to primary human T cells.展开更多
基金supported by the Natural Science Foundation of China (No.81871800 and 82072496)granted to W.D.the Natural Science Foundation of Hebei Province (No.H2020206203)granted to S.Y.+1 种基金a National Health and Medical Research Council (NHMRC)Australia Ideas Grant (No.2011398) granted to D.H.supported by the Assistant Secretary of Defense for Health Affairs endorsed by the US Department of Defense through the FY19 Chronic Pain Management Research Program (D.M.K:award no.W81XWH2010909)。
文摘Low back pain(LBP)is the world's leading cause of disability and is increasing in prevalence more rapidly than any other pain condition.Intervertebral disc(IVD)degeneration and facet joint osteoarthritis(FJOA)are two common causes of LBP,and both occur more frequently in elderly women than in other populations.Moreover,osteoarthritis(OA)and OA pain,regardless of the joint,are experienced by up to twice as many women as men,and this difference is amplified during menopause.Changes in estrogen may be an important contributor to these pain states.Receptors for estrogen have been found within IVD tissue and nearby joints,highlighting the potential roles of estrogen within and surrounding the IVDs and joints.In addition,estrogen supplementation has been shown to be effective at ameliorating IVD degeneration and OA progression,indicating its potential use as a therapeutic agent for people with LBP and OA pain.This review comprehensively examines the relationship between estrogen and these pain conditions by summarizing recent preclinical and clinical findings.The potential molecular mechanisms by which estrogen may relieve LBP associated with IVD degeneration and FJOA and OA pain are discussed.
基金supported by the National Health and Medical Research Council Project Grant (1085359)supported by Prime Minister’s Australia Asia Endeavour Postgraduate (Ph.D.) Award funded by the Australian Government,epartment of Education and Training,UQ international scholarship (UQI) and UQ Centenial scholarship (UQCent)
文摘Nullbasic is a mutant form of HIV-1 Tat that has strong ability to protect cells from HIV-1 replication by inhibiting three different steps of viral replication: reverse transcription, Rev export of viral m RNA from the nucleus to the cytoplasm and transcription of viral m RNA by RNA polymerase II. We previously showed that Nullbasic inhibits transduction of human cells including T cells by HIV-1-based lentiviral vectors. Here we investigated whether the Nullbasic antagonists huTat2(a Tat targeting intrabody), HIV-1 Tat or Rev proteins or cellular DDX1 protein could improve transduction by a HIV-1 lentiviral vector conveying Nullbasic-Zs Green1 to human T cells. We show that overexpression of huTat2, Tat-FLAG and DDX1-HA in virus-like particle(VLP) producer cells significantly improved transduction efficiency of VLPs that convey Nullbasic in Jurkat cells. Specifically, co-expression of Tat-FLAG and DDX1-HA in the VLP producer cell improved transduction efficiency better than if used individually. Transduction efficiencies could be further improved by including a spinoculation step. However, the same optimised protocol and using the same VLPs failed to transduce primary human CD4^+T cells. The results imply that the effects of Nullbasic on VLPs on early HIV-1 replication are robust in human CD4^+T cells. Given this significant block to lentiviral vector transduction by Nullbasic in primary CD4^+T cells, our data indicate that gammaretroviral, but not lentiviral, vectors are suitable for delivering Nullbasic to primary human T cells.