International journal of molecular medicine
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The mechanism of communicating hydrocephalus after subarachnoid hemorrhage (SAH) remains unclear. Revealing a signaling cascade may provide significant insights into the molecular etiology of the accumulation of cerebrospinal fluid (CSF) in cerebral compartments during SAH. ⋯ The cascade of TGF β1-Smad3 was significantly upregulated by TH, which, in turn, stimulated the proliferation of subarachnoid meninges. TH-induced overexpression of TGF-β1 and activation of its downstream factors might be a mechanism of communicating hydrocephalus after SAH.
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The accumulation of foam cells in atherosclerotic lesions is a hallmark of early-stage atherosclerosis. Kaempferol has been shown to inhibit oxidized low-density lipoprotein (oxLDL) uptake by macrophages; however, the underlying molecular mechanisms are not yet fully investigated. In this study, we shown that treatment with kaempferol markedly suppresses oxLDL-induced macrophage foam cell formation, which occurs due to a decrease in lipid accumulation and an increase in cholesterol efflux from THP-1-derived macrophages. ⋯ This increase was reversed following the knockdown of the HO-1 gene using small hairpin RNA (shRNA). Moreover, the kaempferol-mediated attenuation of lipid accumulation and the promotion of cholesterol efflux was also inhibited by HO-1 shRNA. In conclusion, the c-Jun-AP‑1-dependent downregulation of CD36 and the HO-1-dependent upregulation of ABCG1, SR-BI and ABCA1 may mediate the beneficial effects of kaempferol on foam cell formation.
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Elucidation of the mechanisms underlying neuropathic pain is expected to aid in the discovery and selection of effective therapeutic methods. Currently, microRNA (miRNA) is thought to play an important role in the development and maintenance of the nervous system. We, therefore, hypothesized that miRNAs are involved in neuropathic pain, and investigated this possibility by analyzing miRNA expression in the dorsal horn of the spinal cord in a chronic constriction injury (CCI) rat model using the TaqMan® Low Density Array (TLDA). ⋯ Certain miRNAs were reported to be related to neuropathic pain; miR-500, -221 and -21. The expression levels of a large number of miRNAs in the dorsal horn of the spinal cord in CCI rats changed. These results provide a step toward elucidation of the mechanisms underlying neuropathic pain.
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Chronic hepatitis B (CHB) virus infection is caused by compromised host immunity, but the precise underlying mechanism remains unclear. Retinoic acid-inducible gene I (RIG-I) triggers antiviral immunity by inducing interferon-β (IFN-β) production following viral infection. To investigate the role of the RIG-I-IFN-β signaling pathway in monocyte-derived dendritic cells (moDCs) during CHB infection, moDCs were generated by stimulating CD14+ monocytes in vitro. ⋯ To further investigate the function of RIG-I in chronic hepatitis B virus (HBV) infection, HepG2 or HepG2.2.15 (HBV-transformed) cell lines were challenged with VSV following RIG-1 transfection. IFN-β induction was suppressed in HepG2.2.15 cells, but was restored following RIG-I transfection. Taken together, these data indicate that compromised moDC function in CHB patients is attributable to an impaired RIG-I-IFN-β signaling pathway, which results in compromised host viral clearance and HBV persistence in a susceptible population.
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We have previously reported that 5 copies of the hypoxia response element (HRE) can conditionally regulate brain-derived neurotrophic factor gene expression under hypoxic/ischemic conditions in mice. In the present study, we investigated the controlled expression of neurotrophin-3 (NT-3) by HRE under hypoxic conditions and determined the protective effects of conditionally expressed NT-3 on hypoxia-induced apoptosis in PC12 cells. Five copies of the HRE (5HRE) and the simian virus 40 minimal promoter (SV40mp) were employed to construct a cassette, and transfer of therapeutic gene, NT-3, into PC12 cells was achieved using a retroviral vector. ⋯ In addition, the hypoxia-induced upregulation of both p38 and caspase-3 activities was suppressed in 5HRE-NT3 transgenic PC12 cells under hypoxic conditions (P<0.05). Taken together, these results demonstrate that 5HRE-SV40mp regulates NT-3 gene expression in response to hypoxia in PC12 cells. The data presented in this study may prove useful in future gene therapy studies for the treatment of ischemic diseases.