Current Issue : January - March Volume : 2015 Issue Number : 1 Articles : 5 Articles
It is now evident that many nuclear hormone receptors can modulate target gene expression. REV-ERB????, one of the nuclear\nhormone receptors with the capacity to alter clock function, is critically involved in lipid metabolism, adipogenesis, and the\ninflammatory response. Recent studies suggest that REV-ERB???? plays a key role in the mediation between clockwork and\ninflammation. The purpose of the current study was to investigate the role of REV-ERB???? in the regulation of interleukin-6 (il6)\ngene expression in murine macrophages. REV-ERB???? agonists, or over expression of rev-erb???? in the murine macrophage cell line\nRAW264 cells, suppressed the induction of il6 mRNA following a lipopolysaccharide (LPS) endotoxin challenge. Also, rev-erb????\nover expression decreased LPS-stimulated nuclear factor ????B (NF????B) activation in RAW264 cells. We showed that REV-ERB????\nrepresses il6 expression not only indirectly through an NF????B bindingmotif but also directly through a REV-ERB???? bindingmotif in\nthe murine il6 promoter region. Furthermore, peritonealmacrophages frommice lacking rev-erb???? increased il6 mRNA expression.\nThese data suggest that REV-ERB???? regulates the inflammatory response of macrophages through the suppression of il6 expression.\nREV-ERB???? may therefore be identified as a potent anti-inflammatory receptor and be a therapeutic target receptor of inflammatory\ndiseases....
Posttraumatic stress disorder (PTSD) is characterized by the occurrence of a traumatic event that is beyond the normal range\nof human experience. The future of PTSD treatment may specifically target the molecular mechanisms of PTSD. In the US,\napproximately 20% of adults report taking herbal products to treat medical illnesses. L-theanine is the amino acid in green tea\nprimarily responsible for relaxation effects. No studies have evaluated the potential therapeutic properties of herbal medications on\ngene expression in PTSD.We evaluated gene expression in PTSD-induced changes in the amygdala and hippocampus of Sprague-\nDawley rats. The rats were assigned to PTSD-stressed and nonstressed groups that received either saline, midazolam, L-theanine,\nor L-theanine + midazolam. Amygdala and hippocampus tissue samples were analyzed for changes in gene expression. One-way\nANOVA was used to detect significant difference between groups in the amygdala and hippocampus. Of 88 genes examined, 17 had\na large effect size greater than 0.138. Of these, 3 genes in the hippocampus and 5 genes in the amygdala were considered significant\n(???? < 0.05) between the groups. RT-PCR analysis revealed significant changes between groups in several genes implicated in a\nvariety of disorders ranging from PTSD, anxiety, mood disorders, and substance dependence....
Prostate cancer is the most common noncutaneous cancer among men in the United States. A genetic contribution to prostate\ncancer risk has been documented, but knowledge of the molecular mechanisms involved in prostate cancer initiation is still not\nwell understood. Loss of heterozygosity (LOH) of chromosomal regions is crucial in tumor progression. In human prostate cancer,\nseveral chromosomal regions demonstrating a high frequency of LOH have been previously identified. KCTD11 (REN) is a tumor\nsuppressor gene mapping on human chromosome 17p13.2, whose expression is frequently lost in human medulloblastoma and\nin several other cancer types. KCTD11 acts as a negative regulator of the Hedgehog (Hh) signaling. Here, we demonstrated that\nKCTD11 LOH is a common genetic lesion in human prostate adenocarcinoma. Indeed, nuclear KCTD11 protein expression is\nstrongly reduced in primary prostate cancer, and this event correlated with overexpression of proteins acting into the Hedgehog\npathway. Low levels of KCTD11 mRNA have been also observed in prostatic cancer cells, and ectopic overexpression of KCTD11 led\nto growth arrest.Our study demonstrates and supports that KCTD11, as well as negatively regulated downstreameffectors belonging\nto Hh signaling, plays a role in prostate cancer pathogenesis. This could be suitable to characterize new diagnostic and therapeutic\nmarkers....
Valeriana officinalis is one of the most popular medicinal plants commonly used as a sedative and sleep aid. It is suggested that its\npharmacologically active compounds derived from the root may modulate the CYP3A4 gene expression by activation of pregnane\nX receptor (PXR) or constitutive androstane receptor (CAR) and lead to pharmacokinetic herb-drug interactions. The aim of the\nstudy was to determine the influence of valerian on the expression level of CYP3A1 (homologue to human CYP3A4) as well as\nnuclear receptors PXR, CAR, RXR, GR, and HNF-4????. Male Wistar rats were given standardized valerian extract (300mg/kg/day,\np.o.) for 3 and 10 days. The expression in liver tissue was analyzed by using real-time PCR. Our result showed a decrease of CYP3A1\nexpression level by 35% (P = 0.248) and 37% (P < 0.001), respectively. Moreover, Valeriana exhibited statistically significant\nreduction in RXR (approximately 28%) only after 3-day treatment. We also demonstrated a decrease in the amount HNF-4???? by\n22% (P = 0.005) and 32% (P = 0.012), respectively. In case of CAR, the increase of expression level by 46% (P = 0.023) was noted.\nThese findings suggest that Valeriana officinalis extract can decrease the CYP3A4 expression and therefore may lead to interactions\nwith synthetic drugs metabolized by this enzyme....
With the development of nanotechnology, nano carriers have been increasingly used for curative drug/gene delivery. Various\nnano carriers are being introduced and assessed, such as polymer nano particles, liposomes, and micelles. As a novel theranostic\nsystem, nano carriers hold great promise for ultrasound molecular imaging, targeted drug/gene delivery, and therapy.Nanocarriers,\nwith the properties of smaller particle size, and long circulation time, would be advantageous in diagnostic and therapeutic\napplications. Nanocarriers can pass through blood capillary walls and cell membrane walls to deliver drugs. The mechanisms\nof interaction between ultrasound and nanocarriers are not clearly understood, which may be related to cavitation, mechanical\neffects, thermal effects, and so forth. These effects may induce transient membrane permeabilization (sonoporation) on a single cell\nlevel, cell death, and disruption of tissue structure, ensuring noninvasive, targeted, and efficient drug/gene delivery and therapy.The\nsystem has been used in various tissues and organs (in vitro or in vivo), including tumor tissues, kidney, cardiac, skeletal muscle, and\nvascular smooth muscle. In this review, we explore the research progress and application of ultrasound-mediated local drug/gene\ndelivery with nano carriers....
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