ULP-2 SUMO protease regulates UPR and mitochondrial homeostasis in Caenorhabditis elegans.

Mitochondria are the powerhouses of cells, responsible for energy production and regulation of cellular homeostasis. When mitochondrial function is impaired, a stress response termed mitochondrial unfolded protein response (UPRmt) is initiated to restore mitochondrial function. Since mitochondria and UPRmt are implicated in many diseases, it is important to understand UPRmt regulation.

Indoleamine-2,3-dioxygenase in murine and human systemic lupus erythematosus: Down-regulation by the tolerogeneic peptide hCDR1.

וֹndoleamine-2,3-dioxygenase (IDO) plays a role in immune regulation. Increased IDO activity was reported in systemic lupus erythematosus (SLE). We investigated the effects of the tolerogenic peptide hCDR1, shown to ameliorate lupus manifestations, on IDO gene expression.

The tolerogenic peptide hCDR1 immunomodulates cytokine and regulatory molecule gene expression in blood mononuclear cells of primary Sjogren's syndrome patients.

Primary Sjogren's syndrome (pSS) is an autoimmune disease characterized by lymphocytic infiltration of exocrine glands. We investigated whether the tolerogenic peptide, hCDR1, that ameliorates lupus manifestations would have beneficial effects on pSS as well. The in vitro effects of hCDR1 on gene expression of pro-inflammatory cytokines and regulatory molecules were tested in peripheral blood mononuclear cells (PBMC) of 16 pSS patients.

Clostridium difficile infection in hospitalized patients with inflammatory bowel disease: Prevalence, risk factors, and prognosis.

To evaluate the frequency, possible risk factors, and outcome of Clostridium difficile infection (CDI) in inflammatory bowel disease (IBD) patients.There has been an upsurge of CDI in patients with IBD who has been associated with increased morbidity and mortality. Various risk factors have been found to predispose IBD patients to CDI.

The tolerogenic peptide, hCDR1, down-regulates the expression of interferon-α in murine and human systemic lupus erythematosus.

Background: The tolerogenic peptide, hCDR1, ameliorated manifestations of systemic lupus erythematosus (SLE) via the immunomodulation of pro-inflammatory and immunosuppressive cytokines and the induction of regulatory T cells. Because type I interferon (IFN-α) has been implicated to play a role in SLE pathogenesis, we investigated the effects of hCDR1 on IFN-α in a murine model of SLE and in human lupus.

Methodology Principal Findings: (NZBxNZW)F1 mice with established SLE were treated with hCDR1 (10 weekly injections).

Return to flight with multiple sclerosis: aeromedical considerations.

Multiple sclerosis (MS) is the most frequent demyelinating disease of the central nervous system, with versatile manifestations--relapsing-remitting or progressive--and an unpredictable course, with prognoses ranging from minimal neurological impairment to severely disabled. Disease modifying agents can minimize relapse rate and slow disease progression. Yet most patients suffer relapses and progression despite use of these agents.

Induction of hippocampal neurogenesis by a tolerogenic peptide that ameliorates lupus manifestations.

To determine the effect of the tolerogenic peptide hCDR1 on hippocampal neurogenesis, we treated SLE-afflicted (NZBxNZW)F1 mice with hCDR1 (once a week for 10weeks). The treatment resulted in the up-regulation of neurogenesis in the dentate gyrus and restored the NeuN immunoreactivity in brain hippocampi of the mice in association with increased gene expression of IGF-1, NGF and BDNF. Furthermore, hCDR1 treatment significantly up-regulated p-ERK and p-Akt that are suggested to be key components in mediating growth factor-induced neurogenesis.

A role for the B-cell CD74/macrophage migration inhibitory factor pathway in the immunomodulation of systemic lupus erythematosus by a therapeutic tolerogenic peptide.

Systemic lupus erythematosus (SLE) is an autoimmune disease that involves dysregulation of B and T cells. A tolerogenic peptide, designated hCDR1, ameliorates disease manifestations in SLE-afflicted mice. In the present study, the effect of treatment with hCDR1 on the CD74/macrophage migration inhibitory factor (MIF) pathway was studied.

In vivo dynamical interactions between CD4 Tregs, CD8 Tregs and CD4+ CD25- cells in mice.

Background: Regulatory T cells (Tregs) were shown to be central in maintaining immunological homeostasis and preventing the development of autoimmune diseases. Several subsets of Tregs have been identified to date; however, the dynamics of the interactions between these subsets, and their implications on their regulatory functions are yet to be elucidated.

Methodology/principal Findings: We employed a combination of mathematical modeling and frequent in vivo measurements of several T cell subsets.

Atherosclerosis in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease that has a late mortality phase owing mainly to cardiovascular manifestations. Atherosclerosis itself is characterized by inflammatory components, fulfilling the criteria of Witebsky and Rose for an autoimmune disease. SLE patients have increased risk for cardiovascular events, and these are the result of both atherosclerosis and thromboembolic events.

Common infectious agents prevalence in antiphospholipid syndrome.

Antiphospholipid syndrome is characterized by thrombosis and pregnancy loss. Infections are generally associated with autoimmune diseases, but in the setting of antiphospholipid syndrome this link has been suggested as having a pathogenic role. In this study, 98 patients with antiphospholipid syndrome were screened for antibodies directed to several infectious agents.

A new model of induced experimental systemic lupus erythematosus (SLE) in pigs and its amelioration by treatment with a tolerogenic peptide.

Introduction: Systemic lupus erythematosus (SLE) is characterized by a variety of autoantibodies and systemic clinical manifestations. A tolerogenic peptide, hCDR1, ameliorated lupus manifestations in mice models. The objectives of this study were to induce experimental SLE in pigs and to determine the ability of hCDR1 to immunomodulate the disease manifestations.

A tolerogenic peptide down-regulates mature B cells in bone marrow of lupus-afflicted mice by inhibition of interleukin-7, leading to apoptosis.

Systemic lupus erythematosus (SLE) is an autoimmune disease mediated by T and B cells. It is characterized by a variety of autoantibodies and systemic clinical manifestations. A tolerogenic peptide, designated hCDR1, ameliorated the serological and clinical manifestations of SLE in both spontaneous and induced models of lupus.

A tolerogenic peptide that induces suppressor of cytokine signaling (SOCS)-1 restores the aberrant control of IFN-gamma signaling in lupus-affected (NZB x NZW)F1 mice.

Interferon-gamma (IFN-gamma) plays a pathogenic role in systemic lupus erythematosus (SLE). Uncontrolled IFN-gamma signaling may result from a deficiency in the negative regulator, namely, suppressor of cytokine signaling-1 (SOCS-1). We investigated the activation status of IFN-gamma signaling pathway in SLE-afflicted (New-Zealand-BlackxNew-Zealand-White)F1 mice and determined its responsiveness when treating with a tolerogenic peptide, hCDR1, which ameliorates SLE.

Treatment of lupus patients with a tolerogenic peptide, hCDR1 (Edratide): immunomodulation of gene expression.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by dysregulation of cytokines, apoptosis, and B- and T-cell functions. The tolerogenic peptide, hCDR1 (Edratide), ameliorated the clinical manifestations of murine lupus via down-regulation of pro-inflammatory cytokines and apoptosis, up-regulation of the immunosuppressive cytokine TGF-beta, and the induction of regulatory T-cells. In the present study, gene expression was determined in peripheral blood mononuclear cells of 9 lupus patients that were treated for 26 weeks with either hCDR1 (five patients), or placebo (four patients).

The tolerogenic peptide hCDR1 downregulates pathogenic cytokines and apoptosis and upregulates immunosuppressive molecules and regulatory T cells in peripheral blood mononuclear cells of lupus patients.

A tolerogenic peptide, hCDR1, ameliorated murine lupus via the upregulation of functional regulatory cells and by immunomodulating cytokine production. In the present study we analyzed the ability of hCDR1 to similarly affect gene expression and regulatory T cells when incubated with peripheral blood mononuclear cells (PBMC) of lupus patients. To this end, peripheral blood mononuclear cells (PBMC) of 11 lupus patients and five gender- and age-matched healthy controls were cultured with hCDR1 or a control peptide.

B-cell activating factor (BAFF) plays a role in the mechanism of action of a tolerogenic peptide that ameliorates lupus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by dysregulated immune responses mediated by T and B cells. A tolerogenic peptide, designated hCDR1, ameliorated the serological and clinical manifestations of SLE in mouse models of lupus. We investigated the role of B-cell activating factor (BAFF) in the beneficial effects of hCDR1.

Atherosclerosis in autoimmune rheumatic diseases-mechanisms and clinical findings.

Atherosclerosis is one of the major entities leading to morbidity and mortality in the western world. It is known now that atherosclerosis cannot be explained merely by the presence of the Framingham traditional risk factors and that autoimmunity takes a significant role in its pathogenesis. It is also known that individuals with autoimmune diseases demonstrate increased incidence of cardiovascular manifestations and subclinical atherosclerotic disease.

The role of apoptosis in the ameliorating effects of a CDR1-based peptide on lupus manifestations in a mouse model.

Experimental systemic lupus erythematosus (SLE) can be induced in mice following immunization with an anti-DNA mAb expressing a major Id, 16/6Id. Treatment with a peptide, designated human CDR1 (hCDR1; Edratide), that is based on the sequence of CDR1 of the 16/6Id ameliorated disease manifestations. In the present study, we investigated the roles of apoptosis and related molecules in BALB/c mice with induced experimental SLE following treatment with hCDR1.

Altered gene expression in mice with lupus treated with edratide, a peptide that ameliorates the disease manifestations.

Objective: To identify genes that are differently expressed in (NZB x NZW)F(1) mice with established lupus compared with healthy controls, and to determine how gene expression is affected by treatment with hCDR1 (Edratide), a peptide synthesized on the basis of the sequence of the first complementarity-determining region (CDR1) of an autoantibody.

Methods: RNA was extracted from spleen cells of young, disease-free mice and of older mice with systemic lupus erythematosus (SLE) that were treated with hCDR1 or with vehicle alone. Gene expression was assessed using the DNA microarray technique and verified by real-time reverse transcriptase-polymerase chain reaction (RT-PCR).

IL-1 beta-deficient mice are resistant to induction of experimental SLE.

IL-1 is one of the most pleiotropic pro-inflammatory and immunostimulatory cytokines. Overproduction of IL-1 has been shown to be involved in the pathogenicity of various autoimmune inflammatory diseases, including systemic lupus erythematosus (SLE). However, the different contributions that the IL-1 agonistic molecules make in their in vivo native milieu, IL-1beta which is mainly secreted against IL-1alpha which is mainly cell-associated, have not been established.

A peptide based on the complementarity-determining region 1 of an autoantibody ameliorates lupus by up-regulating CD4+CD25+ cells and TGF-beta.

Systemic lupus erythematosus is an autoimmune disease characterized by autoantibodies and systemic clinical manifestations. A peptide, designated hCDR1, based on the complementarity-determining region (CDR) 1 of an autoantibody, ameliorated the serological and clinical manifestations of lupus in both spontaneous and induced murine models of lupus. The objectives of the present study were to determine the mechanism(s) underlying the beneficial effects induced by hCDR1.

Curcumin synergistically potentiates the growth inhibitory and pro-apoptotic effects of celecoxib in pancreatic adenocarcinoma cells.

Background And Aim: Adenocarcinoma of the Pancreas is a leading cause of cancer-related mortality, accounting for an estimated 30,000 deaths per year in the United States. Multiple studies have indicated that specific cyclooxygenase-2 (COX-2) inhibitors may serve in the prevention and treatment of a variety of malignancies including pancreatic adenocarcinoma. Recent studies had shown that the long-term use of high concentration of COX-2 inhibitors is not toxic free and may be limited due to serious gastrointestinal and cardiovascular side effects.

Amelioration of murine lupus by a peptide, based on the complementarity determining region-1 of an autoantibody as compared to dexamethasone: different effects on cytokines and apoptosis.

A peptide (hCDR1) based on the sequence of the complementarity-determining region-1 of an anti-DNA autoantibody ameliorates clinical manifestations of lupus. We analyzed the beneficial effects of hCDR1 when given alone or in combination with dexamethasone, while comparing the mechanisms of action of the latter. Treatment with either hCDR1 or dexamethasone, or a combination of the latter significantly reduced titers of dsDNA-specific autoantibodies, levels of proteinuria, and intensity of glomerular immune complex deposits.

High prevalence of systemic lupus erythematosus in 78 myasthenia gravis patients: a clinical and serologic study.

Objective: The objective of this study was to define the prevalence of systemic lupus erythematosus (SLE) in patients with myasthenia gravis (MG).

Methods: Seventy-eight MG patients recruited unselectively from Israeli MG database were evaluated by medical history, physical examination and serology (ANA at 1:100 and anti-ds-DNA at 1:10 dilution) for the presence of SLE, which was defined by the presence of four or more American College of Rheumatology diagnostic criteria.

Results: Thirty-one (40%) of our patients were males and 47 (60%) were females.