Metabolic changes during evolution of Sjögren's in both an animal model and human patients.

Sjögren's (SS) involves salivary and lacrimal gland dysfunction. These studies examined metabolic profiles in the B6. transgene mouse model of SS and a cohort of human SS patients at different stages of disease.

Association of Systemic Markers of Inflammation with Signs and Symptoms of Dry Eye Disease and Sjogren's Syndrome in the Dry Eye Assessment and Management (DREAM©) Study.

Purpose: To evaluate the possible role of systemic inflammation in dry eye disease (DED) via systemic inflammatory marker associations with DED signs and symptoms, and an analysis of a subgroup with Sjogren's Syndrome (SS).

Methods: Participant serums were analyzed using line immunoassays (LIAs) for the presence of antibodies against 34 systemic inflammatory markers. Using the 2012 American College of Rheumatology definition, the 481 participants were categorized into group 1 (SS;  = 52), group 2 (autoimmune disease not including SS;  = 66), or group 3 (control, i.

Metformin-induced activation of Ca signaling prevents immune infiltration/pathology in Sjogren's syndrome-prone mouse models.

Immune cell infiltration and glandular dysfunction are the hallmarks of autoimmune diseases such as primary Sjogren's syndrome (pSS), however, the mechanism(s) is unknown. Our data show that metformin-treatment induces the salivary glands of IL14α-transgenic mice (IL14α), which is a model for pSS. Mechanistically, we show that loss of in IL14α mice.

Marginal Zone B (MZB) Cells: Comparison of the Initial Identification of Immune Activity Leading to Dacryoadenitis and Sialadenitis in Experimental Sjögren's Syndrome.

Although multiple mouse strains have been advanced as models for Sjögren's syndrome (SS), which is a human systemic autoimmune disease characterized primarily as the loss of lacrimal and salivary gland functions, the C57BL/6.NOD- recombinant inbred (RI) mouse derived from the NOD/ShiLtJ line is considered one of the more appropriate models exhibiting virtually all the characteristics of the human disease. This mouse model, as well as other mouse models of SS, have shown that B lymphocytes are essential for the onset and development of observed clinical manifestations.

Targeting alarmin release reverses Sjogren's syndrome phenotype by revitalizing Ca signalling.

Background: Primary Sjogren's syndrome (pSS) is a systemic autoimmune disease that is embodied by the loss of salivary gland function and immune cell infiltration, but the mechanism(s) are still unknown. The aim of this study was to understand the mechanisms and identify key factors that leads to the development and progression of pSS.

Methods: Immunohistochemistry staining, FACS analysis and cytokine levels were used to detect immune cells infiltration and activation in salivary glands.

Efficacy and Safety of Low-Dose Interleukin 2 for Primary Sjögren Syndrome: A Randomized Clinical Trial.

Importance: Primary Sjögren syndrome (pSS) is a systemic autoimmune disease associated with dysregulated immune cells, with no efficient therapy. There is a need to study potential therapeutic approaches.

Objective: To investigate the efficacy, safety, and immune response of low-dose interleukin 2 (LD-IL-2) in the treatment of pSS.

A Temporal Comparative RNA Transcriptome Profile of the Annexin Gene Family in the Salivary versus Lacrimal Glands of the Sjögren's Syndrome-Susceptible C57BL/6.NOD- Mouse.

A generally accepted hypothesis for the initial activation of an immune or autoimmune response argues that alarmins are released from injured, dying and/or activated immune cells, and these products complex with receptors that activate signal transduction pathways and recruit immune cells to the site of injury where the recruited cells are stimulated to initiate immune and/or cellular repair responses. While there are multiple diverse families of alarmins such as interleukins (IL), heat-shock proteins (HSP), Toll-like receptors (TLR), plus individual molecular entities such as Galectin-3, Calreticulin, Thymosin, alpha-Defensin-1, RAGE, and Interferon-1, one phylogenetically conserved family are the Annexin proteins known to promote an extensive range of biomolecular and cellular products that can directly and indirectly regulate inflammation and immune activities. For the present report, we examined the temporal expression profiles of the 12 mammalian annexin genes ( and ), applying our temporal genome-wide transcriptome analyses of ex vivo salivary and lacrimal glands from our C57BL/6.

A MZB Cell Activation Profile Present in the Lacrimal Glands of Sjögren's Syndrome-Susceptible C57BL/6.NOD- Mice Defined by Global RNA Transcriptomic Analyses.

The C57BL/6.NOD-Aec1Aec2 mouse has been extensively studied to define the underlying cellular and molecular basis for the onset and development of Sjögren's syndrome (SS), a human systemic autoimmune disease characterized clinically as the loss of normal lacrimal and salivary gland functions leading respectively to dry eye and dry mouth pathologies. While an overwhelming majority of SS studies in both humans and rodent models have long focused primarily on pathophysiological events and the potential role of T lymphocytes in these events, recent studies in our murine models have indicated that marginal zone B (MZB) lymphocytes are critical for both development and onset of SS disease.

3,5-Bis(trifluoromethyl)phenylsulfonamides, a novel pancreatic cancer active lead. Investigation of the terminal aromatic moiety.

Virtual screening identified N-(6-((4-bromobenzyl)amino)hexyl)-3,5-bis(trifluoromethyl)benzenesulfonamide (1) a lead compound that bound to the S100A2-p53 binding groove. S100A2 is a Ca binding protein with implications in cell signaling and is known to be upregulated in pancreatic cancer. It is a validated pancreatic cancer drug target.

Upregulated Chemokine and Rho-GTPase Genes Define Immune Cell Emigration into Salivary Glands of Sjögren's Syndrome-Susceptible C57BL/6.NOD- Mice.

The C57BL/6.NOD- mouse is considered a highly appropriate model of Sjögren's Syndrome (SS), a human systemic autoimmune disease characterized primarily as the loss of lacrimal and salivary gland functions. This mouse model, as well as other mouse models of SS, have shown that B lymphocytes are essential for the development and onset of observed clinical manifestations.

On the development of first aid kits composition.

The paper compares the composition of selected types of first aid kits listed in the Czechoslovak branch standards editions (ON 84 6635 First Aid Kits, 1968, 1976, 1989). The authors focused only on evaluating the development of medicine representation. During the study period, a total of 17 medicinal products belonging to the four main ATC groups were represented in wall-mounted first-aid kits, five types of products from the three main ATC groups in travel first-aid kits, and ten types of products from the four main ATC groups in medical bags.

Targeting the S100A2-p53 Interaction with a Series of 3,5-Bis(trifluoromethyl)benzene Sulfonamides: Synthesis and Cytotoxicity.

In silico approaches identified 1, N-(6-((4-bromo- benzyl)amino)hexyl)-3,5-bis(trifluoromethyl)benzene sulfonamide, as a potential inhibitor of the S100A2-p53 protein-protein interaction, a validated pancreatic cancer drug target. Subsequent cytotoxicity screening revealed it to be a 2.97 μM cell growth inhibitor of the MiaPaCa-2 pancreatic cell line.

Early Covert Appearance of Marginal Zone B Cells in Salivary Glands of Sjögren's Syndrome-Susceptible Mice: Initiators of Subsequent Overt Clinical Disease.

The C57BL/6.NOD- mouse model has been extensively studied to define the underlying cellular and molecular bioprocesses critical in the onset of primary Sjögren's Syndrome (pSS), a human systemic autoimmune disease characterized clinically as the loss of lacrimal and salivary gland functions leading to dry eye and dry mouth pathologies. This mouse model, together with several gene knockout mouse models of SS, has indicated that B lymphocytes, especially marginal zone B (MZB) cells, are necessary for development and onset of clinical manifestations despite the fact that destruction of the lacrimal and salivary gland cells involves a classical T cell-mediated autoimmune response.

Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior.

Purpose: We describe a novel neurobehavioral phenotype of autism spectrum disorder (ASD), intellectual disability, and/or attention-deficit/hyperactivity disorder (ADHD) associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis.

Methods: We assembled a cohort of 38 individuals (from 33 unrelated families) with de novo variants in RFX3, RFX4, and RFX7.

Decrease in alpha-1 antiproteinase antitrypsin is observed in primary Sjogren's syndrome condition.

Primary Sjogren's syndrome (pSS) is a systemic autoimmune disease that is characterized by the infiltration of immune cells. Although the loss of salivary gland function is a major manifestation observed in pSS, the factors that could promote these changes in salivary gland tissue in pSS is not yet determined. Herein, we provide evidence that loss of alpha1 antiproteinase antitrypsin could contribute to the induction of pSS.

Carnitine Palmitoyl Transferase Deficiency in a University Immunology Practice.

Purpose: This report describes the clinical manifestations of 35 patients sent to a University Immunology clinic with a diagnosis of fatigue and exercise intolerance who were identified to have low carnitine palmitoyl transferase activity on muscle biopsies.

Recent Findings: All of the patients presented with fatigue and exercise intolerance and many had been diagnosed with fibromyalgia. Their symptoms responded to treatment of the metabolic disease.

Efficacy and safety of low-dose IL-2 in the treatment of systemic lupus erythematosus: a randomised, double-blind, placebo-controlled trial.

Objectives: Open-labelled clinical trials suggested that low-dose IL-2 might be effective in treatment of systemic lupus erythematosus (SLE). A double-blind and placebo-controlled trial is required to formally evaluate the safety and efficacy of low-dose IL-2 therapy.

Methods: A randomised, double-blind and placebo-controlled clinical trial was designed to treat 60 patients with active SLE.

Immunologic Adverse Effects of Biologics for the Treatment of Atopy.

The use of biologic agents as therapies for atopic diseases such as asthma and atopic dermatitis has increased greatly in recent years. The biological agents used to treat atopic diseases are for the most part monoclonal antibodies that suppress the immune response and reduce inflammation by targeting particular cytokines or other molecules involved in Th1, Th2, or Th17 immune reactions. Various side effects and rare complications have been reported from these agents.

Sjogren's Syndrome and TAM Receptors: A Possible Contribution to Disease Onset.

Sjogren's syndrome (SS) is a chronic, progressive autoimmune disease featuring both organ-specific and systemic manifestations, the most frequent being dry mouth and dry eyes resulting from lymphocytic infiltration into the salivary and lacrimal glands. Like the related autoimmune disease systemic lupus erythematosus (SLE), SS patients and mouse models display accumulation of apoptotic cells and a Type I interferon (IFN) signature. Receptor tyrosine kinases (RTKs) of the Tyro3, Axl, and Mer (TAM) family are present on the surface of macrophages and dendritic cells and participate in phagocytosis of apoptotic cells (efferocytosis) and inhibition of Type I IFN signaling.

Serum soluble CD25 as a risk factor of renal impairment in systemic lupus erythematosus - a prospective cohort study.

Objective Serum soluble CD25 (sCD25) could be used as a biomarker for disease activity in conditions associated with T-cell activation including various autoimmune diseases. This study aimed to explore the role of sCD25 as an indicator of disease activity and organ involvement in patients with systemic lupus erythematosus (SLE). Methods Serum samples were collected from 107 SLE patients and 92 age-matched healthy controls (HCs).

P2Y R deletion ameliorates sialadenitis in IL-14α-transgenic mice.

Objective: Interleukin-14α-transgenic (IL-14αTG) mice develop an autoimmune exocrinopathy with characteristics similar to Sjögren's syndrome, including sialadenitis and hyposalivation. The P2Y receptor (P2Y R) for extracellular ATP and UTP is upregulated during salivary gland inflammation (i.e.