Chronic hepatitis C virus (HCV) infection is the leading risk factor for hepatocellular carcinoma (HCC) and chronic liver disease worldwide. Green tea, in addition to being consumed as a healthy beverage, contains phenolic catechins that have been used as medicinal substances. In the present study, we illustrated that the epicatechin isomers (+)-epicatechin and (−)-epicatechin concentration-dependently inhibited HCV replication at nontoxic concentrations by using in vitro cell-based HCV replicon and JFH-1 infectious systems. In addition to significantly suppressing virus-induced cyclooxygenase-2 (COX-2) expression, our results revealed that the anti-HCV activity of the epicatechin isomers occurred through the down-regulation of COX-2. Furthermore, both the epicatechin isomers additively inhibited HCV replication in combination with either interferon-α or viral enzyme inhibitors [2′-C-methylcytidine (NM-107) or telaprevir]. They also had prominent anti-inflammatory effects by inhibiting the gene expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and inducible nitrite oxide synthase as well as the COX-2 in viral protein-expressing hepatoma Huh-7 cells. Collectively, (+)-epicatechin and (−)-epicatechin may serve as therapeutic supplements for treating HCV-related diseases.
SUMMARYTo evaluate the prevalence of coronary artery disease (CAD) in patients with spinal cord injury (SCI), 47 clinically asymptomatic SCI patients received thallium-201 myocardial perfusion single photon emission computed tomography (Tl-201 SPECT) after dipyridamole administration for the diagnosis of CAD. There were 4 groups as follows; group 1: 13 patients with quadriplegia and complete SCI, group 2: 11 patients with quadriplegia and incomplete SCI, group 3: 11 patients with paraplegia and complete SCI, and group 4: 12 patients with paraplegia and incomplete SCI. There were no significant differences in sex distribution, ages, SCI duration, or CAD risk factors among the SCI patients in the 4 groups. All Tl-201 SPECT images were interpreted by the agreement of 2 experienced nuclear medicine physicians without prior knowledge of the patients' histories. A total of 30 of 47 (63.8%) SCI patients had abnormal Tl-201 SPECT findings. Among the 4 groups of SCI patients, those in groups 1 and 4 had the significantly highest and lowest prevalences of abnormal Tl-201 SPECT findings, respectively. We concluded that combined quadriplegia and complete SCI is an important CAD risk factor in SCI patients based on the objective evidence of intravenous dipyridamole cardiac stress testing with Tl-201 SPECT. (Int Heart J 2006; 47: 325-330) Key words: Spinal cord injury, Thallium-201 myocardial perfusion single photon emission computed tomography THERE is a cluster of multiple risk factors for coronary artery disease (CAD) among individuals with spinal cord injury (SCI), 1) but there is little information available on the prevalence of CAD in this population. SCI patients tend to have an increased percentage of body fat and have sedentary life styles. These individuals may not have symptoms despite significant CAD, partially due to their reduced level of activity. SCI patients often undergo rehabilitation programs, exercise training, metabolic testing, and surgical procedures without having their From the
Cyclooxygenase-2 (COX-2) is one of the important mediators of inflammation in response to viral infection, and it contributes to viral replication, for example, cytomegalovirus or hepatitis C virus replication. The role of COX-2 in dengue virus (DENV) replication remains unclear. In the present study, we observed an increased level of COX-2 in patients with dengue fever compared with healthy donors. Consistent with the clinical data, an elevated level of COX-2 expression was also observed in DENV-infected ICR suckling mice. Using cell-based experiments, we revealed that DENV-2 infection significantly induced COX-2 expression and prostaglandin E2 (PGE2) production in human hepatoma Huh-7 cells. The exogenous expression of COX-2 or PGE2 treatment dose-dependently enhanced DENV-2 replication. In contrast, COX-2 gene silencing and catalytic inhibition sufficiently suppressed DENV-2 replication. In an ICR suckling mouse model, we identified that the COX-2 inhibitor NS398 protected mice from succumbing to life-threatening DENV-2 infection. By using COX-2 promoter-based analysis and specific inhibitors against signaling molecules, we identified that NF-κB and MAPK/JNK are critical factors for DENV-2-induced COX-2 expression and viral replication. Altogether, our results reveal that COX-2 is an important factor for DENV replication and can serve as a potential target for developing therapeutic agents against DENV infection.
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