International journal of molecular medicine
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Increased plasma levels of several acute phase proteins, such as C-reactive protein (CRP), have been documented among different patients with chronic renal failure (CRF). The aim of the present study was to determine whether pentraxin-3 (PTX3) is a reliable marker of inflammation in CRF. Plasma samples and monocytes were taken from 43 patients before and after undergoing haemodialysis (HD), from 45 uraemic patients (UR) without HD treatment and from 25 healthy controls. ⋯ In contrast, no changes were observed after HD. A significant correlation among plasma PTX3 versus fibrinogen, TNF-alpha and IL-1beta was observed in HD and UR patients. Collectively, these data suggest that PTX3 protein may represent an additional and stable marker of inflammation in CRF.
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RNA interference (RNAi) mediated by double- stranded small interfering RNA (siRNA) is a novel mechanism of sequence-specific, post-transcriptional gene silencing. There has been much research into the use of RNAi for the treatment of human diseases. Many viruses, including hepatitis B virus (HBV), are susceptible to inhibition by this mechanism. ⋯ Collectively, the PCR-based siRNA expression strategy provides a rapid and easy approach for testing candidate anti-HBV siRNA sequences and for cloning selected siRNA expression cassettes into a vector. RNAi based on the HFV vector was able to achieve effective, long-term inhibition of HBV gene expression and viral DNA replication. The combination of the two techniques may provide a powerful tool in the treatment of viral infection.
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Neuropeptide B/W receptor 1 (NPBWR1) and neuropeptide B/W receptor 2 (NPBWR2) are two structurally related orphan receptors linked to protein G. In rodents NPBWR2 is absent, and its counterpart is described as being similar to neuropeptide B/W receptor 2. Endogenous ligands of these receptors have been identified. ⋯ At 30 min, but not 60, of the experiment, NPW notably lowered blood leptin concentrations at both tested doses. On the contrary, NPB injections had no effect on blood leptin and insulin concentrations. Thus, the results suggest that NPW but not NPB exerts a potent suppressive effect on blood leptin concentrations in the rat, and this mechanism may be involved in NPW regulation of energy homeostasis.
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Hemorrhagic shock followed by resuscitation (HSR) causes neutrophil sequestration in the lung which leads to acute lung injury (ALI). Neutrophil elastase (NE) is thought to play a pivotal role in the pathogenesis of ALI. This study investigated whether sivelestat, a specific NE inhibitor, can attenuate ALI induced by HSR in rats. ⋯ HSR treatment induced lung injury, as demonstrated by pulmonary edema with infiltration of neutrophils, the increase in lung W/D ratio, MPO activity, gene expression of TNF-alpha and iNOS, and DNA-binding activity of NF-kappaB, and enhanced expression of ICAM-1. In contrast, sivelestat treatment significantly ameliorated the HSR-induced lung injury, as judged by the marked improvement in all these indices. These results indicate that sivelestat attenuated HSR-induced lung injury at least in part through an inhibition of the inflammatory signaling pathway, in addition to the direct inhibitory effect on NE.
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Fatty acid synthase (FAS), the key metabolic multi-enzyme that is responsible for the terminal catalytic step in the de novo fatty acid biosynthesis, plays an active role in the development, maintenance, and enhancement of the malignant phenotype in a subset of breast carcinomas. We recently described that a molecular bi-directional cross-talk between FAS and the Her-2/neu (erbB-2) oncogene is taking place at the level of transcription, translation, and activity in breast cancer cells. Because Her-2/neu has been linked with altered sensitivity to cytotoxic drugs, we envisioned that FAS gene expression may represent a novel predictive molecular factor for breast cancer response to chemotherapy in a Her-2/neu-related manner. ⋯ TOP2A protein levels were decreased during treatment with the anti-Her-2/neu antibody trastuzumab while, concomitantly, FAS promoter activity and FAS protein expression were significantly reduced. Of note, when the expression levels of TOP2A protein were analyzed following exposure of SK-Br3 cells to increasing concentrations of the novel slow-binding FAS inhibitor C75, a dose-dependent reduction in TOP2A expression was observed. Although FAS gene is not physically located in the Her-2/neu-TOP2A amplicon, our present findings strongly suggest that a tight functional association between FAS, Her-2/neu and TOP2A genes is taking place in a subset of breast carcinoma cells.