Effect of oral genistein administration in early and late phases of allergic encephalomyelitis

Objective(s): Experimental allergic encephalomyelitis (EAE) is an autoimmune disease validated as animal model of multiple sclerosis (MS). Administration of genistein, a phytoestrogenic component of soy, to mice at the onset of EAE is known to attenuate the clinical signs of the disease. The potential effects of genistein on established EAE is less studied. In the current study, we aimed to compare the effects of genistein administration on EAE severity in early and late phases of the disease. Materials and Methods: The C57BL/6 mice were induced with EAE, using MOG 35-55 and gavaged with genistein (300 mg/kg) either after the appearance of the first clinical sign or 30 days post disease induction for ten days. 24 hr after the last gavage, mice were sacrificed. Brains and spleens were removed for assessing lymphocyte proliferation, cell cytotoxicity, and cytokine profile. Spinal cords were dissected to assess the amount of demyelination using Luxol fast blue/cresyl violet staining. Results: Administering mice with genistein, after the establishment of EAE, did not reverse the clinical signs of disease. However, treating with genistein at the onset of disease alleviated the clinical signs by reducing neuronal demyelination. Genistein suppressed the production of IFN-γ and enhanced IL-10 secretion in splenocyte and brain. Genistein also reduced IL-12 and TNF-α secretion in splenocytes, suppressed the proliferation of T-cells, and reduced the cell cytotoxicity. Conclusion: Genistein oral therapy might only reduce EAE severity if started in early phases of the disease

The Internet Use and Community Involvement in Tehran Iran

This is exploring the impact of the internet on local community involvement in Tehran, Iran. It investigates how the internet changes community involvement and argues that the Internet has created new forms of community involvement instead of local community involvement. This study has employed quantitative research methods. The sample for this research was drawn from the population of Internet users, namely people who accessed and used the Internet in Tehran, Iran. The results of the study indicate that there was no significant correlation between the amount of Internet use and local community involvement. People who spend more time online (high Internet user) do not have a greater local community involvement than people who use Internet less of the time. By contrast in terms of type of Internet use and social capital the study found that people who used the Internet for local news and reading newspapers online were more involved in the local community. The study illustrated that the Internet encourages people to some extent to become involved in the national or global community.nbs

Genistein induces a protective immunomodulatory effect in a mouse model of cervical cancer

Background: Genistein (GEN), a naturally occurring flavonoid present in soy bean, has attracted scientific interest for its possible benefits in cancer. Objective: The potential immunomodulatory effects of genistein on the immune system and against TC-1 tumor cell line were evaluated in adult female C57BL/6 mice. Methods: Mice were treated with GEN 10 days before to 10 days after the tumor induction. Thirty days after the last GEN treatment, lymphocyte proliferation, Lactase Dehydrogenase (LDH) cytolytic activity and cytokine secretion were analyzed in GEN and control groups. Results: The results showed that ingestion of genistein significantly increased lymphocyte proliferation and LDH release. Furthermore, the treatment with genistein also caused a significant increment in interferon gamma (IFN-γ). In addition, the treatment achieved significant therapeutic effect in tumor models compared to the control group. These results indicated that the effect of GEN on tumor growth may be attributed to its effect on lymphocyte proliferation, cytolytic activity and IFN-γ production. Conclusion: These results demonstrate that GEN exerts an immunomodulatory effect in a mouse model of Human Papillomavirus (HPV) associated-cervical cancer

A Modal Series Representation of Genesio Chaotic System

In this paper an analytic approach is devised to represent, and study the behavior of, nonlinear dynamic chaotic Genesio system using general nonlinear modal representation. In this approach, the original nonlinear ordinary differential equations (ODEs) of model transforms to a sequence of linear time- invariant ODEs. By solving the proposed linear ODEs sequence, the exact solution of the original nonlinear problem is determined in terms of uniformly convergent series. Also an efficient algorithm with low computational complexity and high accuracy is presented to find the approximate solution. Simulation results indicate the effectiveness of the proposed method.Comment: International Journal of Instrumentation and Control Systems (IJICS) Vol.2, No.3, July 201

Protection of mice by a λ-based therapeutic vaccine against cancer associated with human papillomavirus type 16

Objective: Human papillomavirus (HPV) oncoproteins (i.e. E6 and E7) are constitutively expressed in cervical cancer cells. The proteins are ideal targets to be used for developing therapeutic vaccines against existing HPV-associated carcinomas. To date, whole bacteriophage ('phage')-λ particles, rather than purified 'naked' DNA, have been described as highly efficient delivery vehicles for a DNA vaccine. Methods: In this study, a safe and efficient λ-based therapeutic cancer vaccine, recombinant λ-ZAP E7 phage, was developed by inserting a HPV16 E7 gene into the Lambda ZAP® cytomegalovirus vector. λ-ZAP E7 phages were employed to immunize mice against the E7-expressing murine tumor cell line (TC-1), which is used as a tumor model in an H-2b murine system. Results: The tumor-bearing mice indicated a significant inhibition of tumor growth after 3 injections of 2 × 1012 particles of recombinant phages. Released lactate dehydrogenase, interferon-γ and granzyme B from spleen cells and lymphocyte proliferation of spleen cells, which all demonstrate the enhancement of cell-mediated immunity, suggested the phages could be a potent gene delivery system in animal models. Conclusion: Our results suggest the recombinant phages can be used as effective biological tools for inducing E7-specific protective immune responses. Hence, the study introduces a possible therapeutic strategy against cervical cancer and other HPV-related neoplasia. Copyright © 2010 S. Karger AG, Basel

A rule-based method for predicting the electrical activation of the heart with cardiac resynchronization therapy from non-invasive clinical data

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Quantifying atrial anatomy uncertainty from clinical data and its impact on electro-physiology simulation predictions

Patient-specific computational models of structure and function are increasingly being used to diagnose disease and predict how a patient will respond to therapy. Models of anatomy are often derived after segmentation of clinical images or from mapping systems which are affected by image artefacts, resolution and contrast. Quantifying the impact of uncertain anatomy on model predictions is important, as models are increasingly used in clinical practice where decisions need to be made regardless of image quality. We use a Bayesian probabilistic approach to estimate the anatomy and to quantify the uncertainty about the shape of the left atrium derived from Cardiac Magnetic Resonance images. We show that we can quantify uncertain shape, encode uncertainty about the left atrial shape due to imaging artefacts, and quantify the effect of uncertain shape on simulations of left atrial activation times

Theoretical investigation of InAs/GaSb type-II pin superlattice infrared detector in the mid wavelength infrared range

In this study, we present the theoretical investigation of type-II InAs/GaSb superlattice p-i-n detector. Kronig-Penney and envelope function approximation is used to calculate band gap energy and superlattice minibands. Variational method is also used to calculate exciton binding energies. Our results show that carriers overlap increases at GaSb/InAs interface on the higher energy side while it decreases at InAs/GaSb interface on the lower energy side with increasing reverse bias due to shifting the hole wavefunction toward to the GaSb/InAs interface decisively. Binding energies increase with increasing electric field due to overall overlap of electron and hole wave functions at the both interfaces in contrast with type I superlattices. This predicts that optical absorption is enhanced with increasing electric field. © 2013 American Institute of Physics

The effects of vitamin D supplementation on interictal serum levels of calcitonin gene-related peptide (CGRP) in episodic migraine patients: Post hoc analysis of a randomized double-blind placebo-controlled trial

Background: Emerging evidence showed promising effects of vitamin D on headaches characteristics. Thus, it seems there is still a need for more researches to clarify the mechanisms by which this vitamin exerts anti-migraine effects. Methods: The present study was conducted as a 16-week randomized double-blind placebo-controlled trial on 80 episodic migraine patients allocated in 2 parallel groups each consisted of 40 patients who received vitamin D 2000 IU/d or placebo. At baseline and after the intervention completion, headache diaries and migraine disability assessment questionnaire (MIDAS) were used to assess migraine related variables in patients. Also, interictal serum concentration of calcitonin gene-related peptide (CGRP) (as the dominant mediator of migraine pain pathogenesis) was evaluated using ELISA method. Results: The mean (SD) of age in the vitamin D and placebo groups was 37 (8) and 38 (12) years, respectively. ANCOVA test adjusted for baseline values, and confounders showed vitamin D supplementation resulted in a significant improvement in MIDAS score after 12 weeks in the intervention group (21.49 (16.22-26.77)) compared to placebo (31.16 (25.51-36.82) P value: 0.016). Moreover, after controlling for baseline levels, and other variables using ANCOVA, CGRP level was appeared to be significantly lower following vitamin D supplementation (153.26 (133.03-173.49) ng/L) than the patients in the placebo arm (188.35 (167.15-209.54) ng/L) (P value = 0.022). Conclusion: According to the current findings, vitamin D supplementation in episodic migraineurs, particularly in those with migraine with aura, may potentially improve migraine headache characteristics and disability probably through attenuating CGRP levels. Therefore, these results could provide a new insight into anti-nociceptive effects of vitamin D; however, more studies are required to confirm our findings. Trial registration: The trial is registered in the Iranian registry of clinical trials (IRCT) at 11 July 2018, with IRCT code: IRCT20151128025267N6. © 2020 The Author(s)

Changes in Cardiac Substrate Transporters and Metabolic Proteins Mirror the Metabolic Shift in Patients with Aortic Stenosis

In the hypertrophied human heart, fatty acid metabolism is decreased and glucose utilisation is increased. We hypothesized that the sarcolemmal and mitochondrial proteins involved in these key metabolic pathways would mirror these changes, providing a mechanism to account for the modified metabolic flux measured in the human heart. Echocardiography was performed to assess in vivo hypertrophy and aortic valve impairment in patients with aortic stenosis (n = 18). Cardiac biopsies were obtained during valve replacement surgery, and used for western blotting to measure metabolic protein levels. Protein levels of the predominant fatty acid transporter, fatty acid translocase (FAT/CD36) correlated negatively with levels of the glucose transporters, GLUT1 and GLUT4. The decrease in FAT/CD36 was accompanied by decreases in the fatty acid binding proteins, FABPpm and H-FABP, the β-oxidation protein medium chain acyl-coenzyme A dehydrogenase, the Krebs cycle protein α-ketoglutarate dehydrogenase and the oxidative phosphorylation protein ATP synthase. FAT/CD36 and complex I of the electron transport chain were downregulated, whereas the glucose transporter GLUT4 was upregulated with increasing left ventricular mass index, a measure of cardiac hypertrophy. In conclusion, coordinated downregulation of sequential steps involved in fatty acid and oxidative metabolism occur in the human heart, accompanied by upregulation of the glucose transporters. The profile of the substrate transporters and metabolic proteins mirror the metabolic shift from fatty acid to glucose utilisation that occurs in vivo in the human heart