26,741 research outputs found

    Biological effects of cigarette smoke in cultured human retinal pigment epithelial cells.

    Get PDF
    The goal of the present study was to determine whether treatment with cigarette smoke extract (CSE) induces cell loss, cellular senescence, and extracellular matrix (ECM) synthesis in primary human retinal pigment epithelial (RPE) cells. Primary cultured human RPE cells were exposed to 2, 4, 8, and 12% of CSE concentration for 24 hours. Cell loss was detected by cell viability assay. Lipid peroxidation was assessed by loss of cis-parinaric acid (PNA) fluorescence. Senescence-associated ß-galactosidase (SA-ß-Gal) activity was detected by histochemical staining. Expression of apolipoprotein J (Apo J), connective tissue growth factor (CTGF), fibronectin, and laminin were examined by real-time PCR, western blot, or ELISA experiments. The results showed that exposure of cells to 12% of CSE concentration induced cell death, while treatment of cells with 2, 4, and 8% CSE increased lipid peroxidation. Exposure to 8% of CSE markedly increased the number of SA-ß-Gal positive cells to up to 82%, and the mRNA expression of Apo J, CTGF, and fibronectin by approximately 3-4 fold. Treatment with 8% of CSE also increased the protein expression of Apo J and CTGF and the secretion of fibronectin and laminin. Thus, treatment with CSE can induce cell loss, senescent changes, and ECM synthesis in primary human RPE cells. It may be speculated that cigarette smoke could be involved in cellular events in RPE cells as seen in age-related macular degeneration

    Chronic CSE Treatment Induces the Growth of Normal Oral Keratinocytes via PDK2 Upregulation, Increased Glycolysis and HIF1α Stabilization

    Get PDF
    Exposure to cigarette smoke is a major risk factor for head and neck squamous cell carcinoma (HNSCC). We have previously established a chronic cigarette smoke extract (CSE)-treated human oral normal keratinocyte model, demonstrating an elevated frequency of mitochondrial mutations in CSE treated cells. Using this model we further characterized the mechanism by which chronic CSE treatment induces increased cellular proliferation.We demonstrate that chronic CSE treatment upregulates PDK2 expression, decreases PDH activity and thereby increases the glycolytic metabolites pyruvate and lactate. We also found that the chronic CSE treatment enhanced HIF1α accumulation through increased pyruvate and lactate production in a manner selectively reversible by ascorbate. Use of a HIF1α small molecule inhibitor blocked the growth induced by chronic CSE treatment in OKF6 cells. Furthermore, chronic CSE treatment was found to increase ROS (reactive oxygen species) production, and application of the ROS scavengers N-acetylcysteine abrogated the expression of PDK2 and HIF1α. Notably, treatment with dichloroacetate, a PDK2 inhibitor, also decreased the HIF1α expression as well as cell proliferation in chronic CSE treated OKF6 cells.Our findings suggest that chronic CSE treatment contribute to cell growth via increased ROS production through mitochondrial mutations, upregulation of PDK2, attenuating PDH activity thereby increasing glycolytic metabolites, resulting in HIF1α stabilization. This study suggests a role for chronic tobacco exposure in the development of aerobic glycolysis and normoxic HIFα activation as a part of HNSCC initiation. These data may provide insights into development of chemopreventive strategies for smoking related cancers

    The predictive value of trauma-related coping self-efficacy for posttraumatic stress symptoms:Differences between treatment seeking and non-treatment seeking victims

    Get PDF
    Objective: To assess and compare the (independent) predictive value of trauma-related coping selfefficacy (CSE) for posttraumatic stress symptoms (PTSS) among a treatment sample and a comparison group of nontreatment seeking victims. Method: Both the treatment (N 54) and comparison group (N 144) were exposed to potentially traumatic events (PTEs), experienced a heightened level of PTSS (IES 19), and were matched on work status and time between PTE and first measurement (T1).Respondents completed both baseline (T1) and follow-up measures (T2) approximately 8 months after T1. Results: Multiple regression analyses among the treatment sample showed that neither PTSS at T1 (start of treatment) nor CSE levels at T1 predicted PTSS at T2 among the treatment group. Among the comparison group, higher CSE levels at T1 and younger age were significantly associated with lower PTSS at T2. In both the treatment group and the comparison group PTSS levels were significantly lower at T2 than at T1. As expected, treatment seeking victims have higher PTSS and lower CSE levels than nontreatment seeking victims. Conclusions: Pretreatment CSE did not affect recovery during treatment: higher pretreatment CSE perceptions do not give treated individuals an advantage while CSE is predictive of PTSS among untreated victims

    Cigarette Smoke Extract Stimulates Rat Pulmonary Artery Smooth Muscle Cell Proliferation via PKC-PDGFB Signaling

    Get PDF
    Accumulating evidence suggests a direct role for cigarette smoke in pulmonary vascular remodeling, which contributes to the development of pulmonary hypertension. However, the molecular mechanisms underlying this process remain poorly understood. Platelet-derived growth factor (PDGF) is a potential mitogen and chemoattractant implicated in several biological processes, including cell survival, proliferation, and migration. In this study, we investigated the effect of cigarette smoke extract (CSE) on cell proliferation of rat pulmonary artery smooth muscle cells (rPASMCs). We found that stimulation of rPASMCs with CSE significantly increased cell proliferation and promoted cell cycle progression from G1 phase to the S and G2 phases. CSE treatment also significantly upregulated the mRNA and protein levels of PDGFB and PDGFRβ. Our study also revealed that Rottlerin, an inhibitor of PKCδ signaling, prevented CSE-induced cell proliferation, attenuated the increase of S and G2 phase populations induced by CSE treatment, and downregulated PDGFB and PDGFRβ mRNA and protein levels in rPASMCs exposed to CSE. Collectively, our data demonstrated that CSE-induced cell proliferation of rPASMCs involved upregulation of the PKCδ-PDGFB pathway

    Effect of Turmeric and Carrot Seed Extracts on Serum Liver Biomarkers and Hepatic Lipid Peroxidation, Antioxidant Enzymes and Total Antioxidant Status in Rats

    Get PDF
    Introduction: Pathogenic role of free radicals are well known in various metabolic diseases. They originate from internal and external sources of body. Essential roles of antioxidant defense system for cellular redox regulation and free radical scavenging activity were described in this study. Many in vitro investigations have shown that turmeric (TE) and carrot seed extract (CSE) exhibits to possess antioxidant activities. In this study, we evaluated the antioxidant potentials of ethanolic TE and CSE based on in vivo experiment in the rats. Methods: Animals were assigned to six groups: the 1st and 2nd groups were control groups and 2nd group received 0.2 ml dimethyl sulphoxide as vehicle treated group; other four experimental groups received different doses of TE (100, 200 mg/kg b.w.) and CSE (200, 400 mg/kg b.w.) by gavages, respectively for a period of one month. The indicators of oxidative stress, lipids peroxidation, markers of hepatocyte injury and biliary function markers were measured. Results: The levels of superoxide dismutase, catalase, and glutathione peroxidase were significantly stimulated in the hepatic tissue of treatment groups. The malondialdehyde contents of liver tissue were significantly reduced in the groups fed with TE and CSE. Serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, in treated groups were found to be significantly decreased, whereas albumin and total protein increased as compared to the control groups (P<0.05). Conclusion: this study showed that the regular intake of TE and CSE through the diet can improve antioxidant status and inhibit peroxidation activity in the liver tissue so that using these extracts may protect tissue oxidative stress

    Use Of Core Stabilization Exercise And Medical Exercise Therapy In The Treatment Of A Patient With Chronic Post Partum Low Back Pain: A Case Report

    Get PDF
    Low back pain and lumbar hyper-mobility are common during and after pregnancy. Chronic postpartum low back pain (LBP) can be difficult to manage. Core stabilization exercises (CSE) have been shown to improve function and reduce pain in patients with chronic LBP due to lumbar instability. Medical Exercise Therapy (MET) has shown good outcomes in reducing pain in patients with LBP but has not been thoroughly investigated in the treatment of chronic post partum LBP. There is limited research reporting the use of a combined treatment protocol utilizing CSE and MET in the treatment of chronic LBP in postpartum women. The purpose of this case report was to investigate a combined physical therapy treatment protocol of CSE and MET on a patient with chronic low back pain 2 years post-partum.https://dune.une.edu/pt_studcrposter/1079/thumbnail.jp

    H2S and homocysteine control a novel feedback regulation of cystathionine beta synthase and cystathionine gamma lyase in cardiomyocytes.

    Get PDF
    Hydrogen sulfide (H2S), a cardioprotective gas, is endogenously produced from homocysteine by cystathionine beta synthase (CBS) and cystathionine gamma lyase (CSE) enzymes. However, effect of H2S or homocysteine on CBS and CSE expression, and cross-talk between CBS and CSE are unclear. We hypothesize that homocysteine and H2S regulate CBS and CSE expressions in a dose dependent manner in cardiomyocytes, and CBS deficiency induces cardiac CSE expression. To test the hypothesis, we treated murine atrial HL1 cardiomyocytes with increasing doses of homocysteine or Na2S/GYY4137, a H2S donor, and measured the levels of CBS and CSE. We found that homocysteine upregulates CSE but downregulates CBS whereas Na2S/GYY4137 downregulates CSE but upregulates CBS in a dose-dependent manner. Moreover, the Na2S-treatment downregulates specificity protein-1 (SP1), an inducer for CSE, and upregulates miR-133a that targets SP1 and inhibits cardiomyocytes hypertrophy. Conversely, in the homocysteine-treated cardiomyocytes, CBS and miR-133a were downregulated and hypertrophy was induced. In vivo studies using CBS+/-, a model for hyperhomocysteinemia, and sibling CBS+/+ control mice revealed that deficiency of CBS upregulates cardiac CSE, plausibly by inducing SP1. In conclusion, we revealed a novel mechanism for H2S-mediated regulation of homocysteine metabolism in cardiomyocytes, and a negative feedback regulation between CBS and CSE in the heart

    Lycopene Inhibits NF-kB-Mediated IL-8 Expression and Changes Redox and PPARγ Signalling in Cigarette Smoke–Stimulated Macrophages

    Get PDF
    Increasing evidence suggests that lycopene, the major carotenoid present in tomato, may be preventive against smoke-induced cell damage. However, the mechanisms of such a prevention are still unclear. The aim of this study was to investigate the role of lycopene on the production of the pro-inflammatory cytokine IL-8 induced by cigarette smoke and the possible mechanisms implicated. Therefore, human THP-1 macrophages were exposed to cigarette smoke extract (CSE), alone and following a 6-h pre-treatment with lycopene (0.5–2 µM). CSE enhanced IL-8 production in a time- and a dose-dependent manner. Lycopene pre-treatment resulted in a significant inhibition of CSE-induced IL-8 expression at both mRNA and protein levels. NF-kB controlled the transcription of IL-8 induced by CSE, since PDTC prevented such a production. Lycopene suppressed CSE-induced NF-kB DNA binding, NF-kB/p65 nuclear translocation and phosphorylation of IKKα and IkBα. Such an inhibition was accompanied by a decrease in CSE-induced ROS production and NOX-4 expression. Lycopene further inhibited CSE-induced phosphorylation of the redox-sensitive ERK1/2, JNK and p38 MAPKs. Moreover, the carotenoid increased PPARγ levels which, in turn, enhanced PTEN expression and decreased pAKT levels in CSE-exposed cells. Such effects were abolished by the PPARγ inhibitor GW9662. Taken together, our data indicate that lycopene prevented CSE-induced IL-8 production through a mechanism involving an inactivation of NF-kB. NF-kB inactivation was accompanied by an inhibition of redox signalling and an activation of PPARγ signalling. The ability of lycopene in inhibiting IL-8 production, NF-kB/p65 nuclear translocation, and redox signalling and in increasing PPARγ expression was also found in isolated rat alveolar macrophages exposed to CSE. These findings provide novel data on new molecular mechanisms by which lycopene regulates cigarette smoke-driven inflammation in human macrophages

    Aktivitas Superoksida Dismutase Tikus Diabetes yang Diberi Ekstrak Batang Kapulaga dan Glibenklamid

    Get PDF
    Superoxide Dismutase (SOD) is an antioxidant enzyme which reduce anion superoxide radicals as well as known caused of diabetes. There are many natural additive was believed having capacity to repaired an antioxidant celluler status. Cardamom's stem were reported containing flavonoid and vitamin C which have been proven as in vitro antioxidant. There was no data showing its in vivo potency. This study aims to knoe the SOD activity of diabetes rats which were given cardamom stem extract (CSE) and glibenclamide. The research carried out with the use of experimentally Randomized Design Complete (RAL) by administering treatment on diabetes rat without CSE and glibenclamide as a control, consist of 100 mg/kg bodymass CSE and 2 mg/kg bodymass glibenclamide. The experiment consists of 3 treatments with 7 repetitions, blood sampling carried out experiments as much as 3 times with intervals of 7 days once. The data was analyzed using a variety of analysis (ANOVA). The result showed that the SOD activity increased from 4261 Unit/mg protein to 6604,668 Unit/mg protein (P<0.01) in diabetes rats treatment by CSE for 14 days
    corecore