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“Mo'ez Al-Islam” E. Faris Safia Kacimi Ref'at A. Al-Kurd Mohammad A. Fararjeh Yasser K. Bustanji Mohammad K. Mohammad Mohammad L. Salem 《Nutrition Research》2012
Intermittent fasting and caloric restriction have been shown to extend life expectancy and reduce inflammation and cancer promotion in animal models. It was hypothesized that intermittent prolonged fasting practiced during the month of Ramadan (RIF) could positively affect the inflammatory state. To investigate this hypothesis, a cross-sectional study was designed to investigate the impact of RIF on selected inflammatory cytokines and immune biomarkers in healthy subjects. Fifty (21 men and 29 women) healthy volunteers who practiced Ramadan fasting were recruited for the investigation of circulating proinflammatory cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor α), immune cells (total leukocytes, monocytes, granulocytes, and lymphocytes), and anthropometric and dietary assessments. The investigations were conducted 1 week before Ramadan fasting, at the end of the third week of Ramadan, and 1 month after the cessation of Ramadan month. The proinflammatory cytokines IL-1β, IL-6, and tumor necrosis factor α; systolic and diastolic blood pressures; body weight; and body fat percentage were significantly lower (P < .05) during Ramadan as compared with before Ramadan or after the cessation of Ramadan fasting. Immune cells significantly decreased during Ramadan but still remained within the reference ranges. These results indicate that RIF attenuates inflammatory status of the body by suppressing proinflammatory cytokine expression and decreasing body fat and circulating levels of leukocytes. 相似文献
13.
Safia Al abrawi Marine Fouillet-Desjonqueres Louis David Xavier Barral Pierre Cochat Rolando Cimaz 《Pediatric rheumatology online journal》2008,6(1):17
Takayasu arteritis (TA) is a large vessel vasculitis that usually affects young female patients during the second and third
decades of life, but has been reported in children as young as 24 months of age. Aim of this report was to describe four children
(two girls) with TA, as well as summarizing main published studies. The mean age at presentation of our cases was 11 years
(range 8–15). Three patients were Caucasians and one Asian. Arterial hypertension was the commonest mode of presentation followed
by systemic symptoms. Other related symptoms were due to ischemia and consisted of abdomen, chest, and limb pain. An abdominal
bruit was noted in only one patient. Inflammation markers were always abnormal. Angiography was performed in all cases; left
subclavian artery and common carotid artery were more frequently involved. Renal artery stenosis was observed in two patients.
One boy was diagnosed as having an associated immune deficiency (Wiskott-Aldrich syndrome). Treatment modalities included
prednisone (n = 4), methotrexate (n = 3), and mycophenolate mofetil (MMF) (n = 1). Surgery was required in two patients. Follow-up
ranged from 3 to 10 years since diagnosis. In three cases antihypertensive drugs and methotrexate were stopped, and prednisone
was reduced to 7.5 mg/day. 相似文献
14.
Enhancement of camptothecin-induced cytotoxicity with UCN-01 in breast cancer cells: abrogation of S/G2 arrest 总被引:3,自引:0,他引:3
Purpose: To determine the ability of UCN-01 to abrogate the cell cycle arrest induced by camptothecin (CPT) in tumor cells that lack
p53 function, and therefore enhance the cytotoxicity of CPT in these cells in relation to normal cells with wild-type p53.
Methods: The responses of MDA-MB-231 and GI 101A breast cancer cells were compared to those of normal bovine endothelial cells. Cytotoxicity
was assessed by the MTT assay, and the resulting data were modeled using median-effect analysis. Inhibition of DNA synthesis
was determined by loss of [3H]thymidine incorporation, and cell cycle status was determined by flow cytometric analysis of propidium-iodide-stained nuclei.
Results: UCN-01, a specific inhibitor of protein kinase C (PKC) presently in clinical trials, abrogated CPT-induced activation of
S and G2 checkpoints in human MDA-MB-231 and GI 101A breast carcinoma cells, both of which are mutants for the p53 gene. This abrogation
occurred with the use of sublethal doses (100 nM) of UCN-01 and correlated with the enhancement of CPT-induced cytotoxicity. Median-effect analysis showed that synergistic
cytotoxic interactions existed between CPT and UCN-01 against these tumor cells. In normal cells, however, abrogation of the
S phase arrest caused accumulation in G0/G1 phase, perhaps by the presence of wild-type p53 activity, with no change in CPT-induced cytotoxicity. Conclusion: We have shown previously that the cytotoxicity of CPT is correlated with cell cycle response in normal and tumor cells.
Low doses of CPT arrest cells in the G2/M phase and inhibit DNA synthesis, but higher doses cause arrest of cells in S phase. Thus modulation of events at the S
and G2 checkpoints may provide an opportunity to enhance CPT-induced cytotoxicity in tumor cells. The results of this study indicate
that UCN-01 enhances the progression of tumor cells through S phase thus greatly increasing CPT-induced cytotoxicity. Normal
cells, however, are able to arrest in G0/G1 and thus avoid the increased toxicity induced by CPT. Our findings suggest potential usefulness of combining UCN-01 in topoisomerase
I inhibitor-based drug therapy for the treatment of breast cancer with a dysfunctional p53 gene.
Received: 25 February 1999 / Accepted: 4 October 1999 相似文献
15.
Tawfik A Jin L Banes-Berceli AK Caldwell RB Ogbi S Shirley A Barber D Catravas JD Stern DM Fulton D Caldwell RW Marrero MB 《Vascular pharmacology》2005,43(5):320-326
The generation of reactive oxygen species (ROS) has been implicated in the perturbation of endothelial function and cell death. However, the specific signaling pathways which mediate and modifying this response have not been fully elucidated. Therefore, in this study we tested the hypothesis that activation of JAK2 is involved in the aortic endothelial cell (EC) response to ROS. When ECs were exposed to HG (25 mM) for 6 h or ROS (i.e., H(2)O(2) (100 microM)) for 1 h and returned to normal medium we found a decrease in cell density and morphologic signs of apoptosis. Furthermore, incubation of ECs with HG and H(2)O(2) also resulted in the tyrosine phosphorylation of JAK2. In addition, pretreatment of ECs with AG-490, an inhibitor of JAK2, prevented nuclear fragmentation, whereas inhibitors of Jun kinase (SP 600125), MAP kinase (PD 98059), Src kinase (PP2) or PI-3 kinase (wortmannin) were without effect. Finally, immunoblot analysis of caspase-3 and PARP cleavage confirmed a role for activation of JAK2 in both HG- or ROS-induced apoptosis, based on inhibition by either AG-490 or adenoviral transfection with a dominant-negative JAK2 mutant. In conclusion the activation of JAK2 plays a pivotal role in oxidant stress-induced commitment of ECs to apoptosis, based on studies with HG and H(2)O(2). 相似文献
16.
Ogbi M Wingard CJ Ogbi S Johnson JA 《Naunyn-Schmiedeberg's archives of pharmacology》2004,370(4):251-261
We have observed a lengthening of the duration between spontaneous cardiac contractions under conditions that preferentially activate the epsilon protein kinase C (PKC) isozyme. Therefore, we investigated whether this response could be selectively mediated by PKC in neonatal cardiac myocytes (NCMs) and adult rat ventricular trabeculae. Contraction of NCMs was monitored using light scattering techniques and trabecular force generation was monitored in tissue baths using a force transducer. The involvement of the PKC isozyme was confirmed using an PKC-selective translocation inhibitor and Western blot translocation assays. In NCMs 3 nM 4- phorbol 12-myristate-13-acetate (PMA) treatment preferentially activates (translocates) PKC. In this study 3 nM 4- PMA induced a 2-fold increase in contractile amplitude and a 14-fold increase in the quiescent period between contractions in NCMs. Extracellular adenosine 5-triphosphate (ATP) also enhanced contractile amplitude by 1.7-fold and the quiescent period duration by 8-fold. The enhancement of quiescent period duration was attenuated by an PKC-selective translocation inhibitor. To investigate these relationships in intact myocardium, we studied spontaneously beating adult rat ventricular trabecula. In these fibers contractile amplitude was only modestly enhanced; however, the quiescent period was lengthened by 4.5-fold following a 15-min exposure to 3 nM 4- PMA. 4- PMA treatment also promoted arrhythmogenesis and increased the association of PKC with the particulate fraction in these fibers. Our results suggest that PKC may influence a specific phase of ventricular myocyte spontaneous beating. A better understanding of PKC modulation of spontaneous cardiac contraction may improve our understanding of the molecular events contributing to ventricular automaticity. 相似文献
17.
This study aimed towards probing the role of peroxynitrite damaged human DNA (ONOO–-DNA) in the induction of circulating antibodies in certain cancers of gynecologic origin. We have compared the binding specificity of DNA isolated from the lymphocytes of cancer patients with that of the experimentally modified DNA. Also, the induced anti-ONOO−-DNA antibodies have been used to probe oxidative damage in the DNA isolated from cancer patients. Human placental DNA was modified with peroxynitrite (ONOO−) and analyzed by ultraviolet (UV) and fluorescence spectroscopy, gel electrophoresis, thermal denaturation profile, etc. Antibodies against modified DNA were induced in experimental animals. Specific binding of the antibodies was evaluated by ELISA and band shift assay. 91 cancer patients were selected and grouped according to the type of cancer. Specific binding characteristics of circulating autoantibodies (IgG) were determined by competitive-inhibition ELISA, using different inhibitors. Maximum inhibition of antibody activity by ONOO−-DNA reflected specific recognition of modified epitopes by cancer IgG. This shows generation of neo-epitopes on DNA, upon modification with ONOO−, that are recognized by cancer IgG. Our results indicate epitope sharing between the DNA isolated from cancer patients and the in-vitro modified ONOO−-DNA. The possible role of nitrosative stress in the gynecologic oncology has been discussed. 相似文献
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Epidermal‐like architecture obtained from equine keratinocytes in three‐dimensional cultures
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Ruchi Sharma Safia Z. Barakzai Sarah E. Taylor F. Xavier Donadeu 《Journal of tissue engineering and regenerative medicine》2016,10(8):627-636
Despite the high prevalence of skin conditions in the horse, there is a dearth of literature on the culture and biology of equine skin cells, and this is partially attributable to the lack of suitable in vitro skin models. The objective of this study was to develop a three‐dimensional (3D) culture system that would support the proliferation and differentiation of equine keratinocytes, similar to that observed in natural epidermis. Cell monolayers were obtained from explants of equine skin and serially passaged as highly pure keratinocyte populations (> 95% of cells), based on their expression of cytokeratins, including CK‐5 and CK‐14, which are associated in vivo with proliferating keratinocyte populations. Explant‐derived keratinocytes were seeded into Alvetex? 3D tissue scaffolds for 30 days under conditions that promote cell differentiation. Ultrastructural, immunohistochemical and biochemical analyses revealed that keratinocytes within scaffolds were able to proliferate and attain tissue polarity, including differentiation into basal and suprabasal layers. The basal layer contained distinct cuboidal cells with large nuclei and stained for proliferative markers such as CK‐5 and CK‐14. In contrast, the suprabasal layers consisted of cells with distinct polyhedral morphology, abundant cytoplasmic processes and desmosomes indicative of stratum spinosum and distinct flattened cornified cells that expressed involucrin, a marker of terminal differentiation. Thus, keratinocytes derived from primary equine skin explants were able to attain epidermal‐like architecture in culture. This novel system could provide a very useful tool for modelling skin diseases, drug testing/toxicity studies and, potentially, equine regenerative medicine. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献