Allergen-induced NLRP3/caspase1/IL-18 signaling initiate eosinophilic esophagitis and respective inhibitors protect disease pathogenesis.

The current report describes a stepwise mechanistic pathway of NLRP3/caspase1/IL-18-regulated immune responses operational in eosinophilic esophagitis (EoE). We show that esophageal epithelial cells and macrophage-derived NLRP3 regulated IL-18 initiate the disease and induced IL-5 facilitates eosinophil growth and survival. We also found that A.

Nanofabrication of cobalt-tellurium using Allium sativum extract and its protective efficacy against HO-induced oxidative damage in HaCaT cells.

Allium sativum (A. sativum)is well known for its therapeutic and culinary uses. Because of their high medicinal properties, the clove extract was selected to synthesize cobalt-tellurium nanoparticles.

IL-18-mediated neutrophil recruitment promotes acute lung injury in inflammation-mediated chronic pancreatitis.

Lung injury is the most common secondary complication of pancreatitis and pancreatic malignancy. Around 60-70% of pancreatitis-related deaths are caused by lung injury; however, there is no animal model of the inflammation-mediated progressive pulmonary pathological events that contribute to acute lung injury in chronic pancreatitis (CP). Hence, we developed an inflammation-mediated mouse model and studied the pathological events that have a critical role in promoting the pathogenesis of lung injury.

Cardiovascular Dysfunction in Intrauterine Growth Restriction.

Purpose Of Review: We highlight important new findings on cardiovascular dysfunction in intrauterine growth restriction.

Recent Findings: Intrauterine growth restriction (IUGR) is a multifactorial condition which negatively impacts neonatal growth during pregnancy and is associated with health problems during the lifespan. It affects 5-15% of all pregnancies in the USA and Europe with varying percentages in developing countries.

Development and Characterization of Novel Chronic Eosinophilic Inflammation- Mediated Murine Model of Malignant Pancreatitis.

Aims: Develop a novel murine models of malignant pancreatitis.

Background: Although patients with chronic pancreatitis are at a greater risk of developing pancreatic cancer, there is no definitive mouse model that currently develops chronic pancreatitis-induced pancreatic cancer.

Objective: Characterization of eosinophilic inflammation-mediated malignant pancreatitis in novel murine model.

Molecules involved in the development of Barrett's esophagus phenotype in chronic eosinophilic esophagitis.

This paper aims to investigate the molecules involved in development of Barrett's esophagus (BE) in human eosinophilic esophagitis (EoE). Histopathological, immunohistochemical, real-time PCR Immuno blot, and ELISA analyses are performed to identify the signature genes and proteins involved in the progression of BE in EoE. We detected characteristic features of BE like intermediate columnar-type epithelial cells, induced BE signature genes like in the esophageal mucosa of patients with EoE.

Role of IL-18-transformed CD274-expressing eosinophils in promoting airway obstruction in experimental asthma.

Background: IL-5-dependent residential and IL-18-transformed pathogenic eosinophils have been reported; however, the role of IL-18-transformed CD274-expressing pathogenic eosinophils compared to IL-5-generated eosinophils in promoting airway obstruction in asthma has not yet been examined.

Methods: Eosinophils are detected by tissue anti-MBP and anti-EPX immunostaining, CD274 expression by flow cytometry, and airway resistance using the Buxco FinePointe RC system.

Results: We show that A.

Vaccine efficacy in mutant SARS-CoV-2 variants.

Many aspects of the SARS-CoV-2 virus remain poorly understood, including its rapid mutation and its effects on populations of different ages. The present literature of review is focused on the effectiveness of current available vaccines in view of immerging several SARS-CoV-2 variants. The most dangerous and infectious SARS-CoV-2 strain, B117, was recently discovered in the United Kingdom, and another new variant, 501.

Eosinophils and T cell surface molecule transcript levels in the blood differentiate eosinophilic esophagitis (EoE) from GERD.

We recently rereported that blood mRNA levels of T cells and IgE receptors are the novel non-invasive biomarkers for eosinophilic esophagitis (EoE) with the aim to establish the panel of T cells and IgE receptor as the novel non-invasive biomarkers for EoE. In addition to earlier proposed cell surface molecules, we now added T cell receptor CXCR6 and eosinophils expressed cell surface molecules CD101 and CD274 mRNA levels. The mRNA levels of eosinophils cell surface molecule CD101 and CD274 and T cell receptor CXCR6, Vβ11, CD1d and chemokine CXCL16 levels were examined using the blood of normal, EoE and GERD patients.

Macrophages-induced IL-18-mediated eosinophilia promotes characteristics of pancreatic malignancy.

Reports indicate that accumulated macrophages in the pancreas are responsible for promoting the pathogenesis of chronic pancreatitis (CP). Recently, macrophage-secreted cytokines have been implicated in promoting pancreatic acinar-to-ductal metaplasia (ADM). This study aims to establish the role of accumulated macrophage-activated NLRP3-IL-18-eosinophil mechanistic pathway in promoting several characteristics of pancreatic malignancy in CP.

Chronic inflammation promotes epithelial-mesenchymal transition-mediated malignant phenotypes and lung injury in experimentally-induced pancreatitis.

Patients with chronic pancreatitis have an increased risk of pancreatic malignancy, but the mechanisms underlying this relationship are poorly understood. We developed a mouse model of chronic pancreatitis by treatment with a combination of cerulein and azoxymethane. In our model, we show that cerulein and azoxymethane treated mice develop pathological malignant phenotype and associated lung inflammation.

Blood mRNA levels of T cells and IgE receptors are novel non-invasive biomarkers for eosinophilic esophagitis (EoE).

Eosinophilic esophagitis (EoE) is often misdiagnosed as GERD; therefore, the goal of the current study is to establish a non-invasive diagnostic and monitoring biomarker that differentiated GERD from EoE. Reports indicates that IL-15 responsive iNKT cells and tissue specific IgE have a critical in EoE pathogenesis, not in GERD. Therefore, we tested the hypothesis that the panel of IL-15-responsive T cell and IgE receptors may be novel non-invasive biomarkers for EoE.

Eosinophils in the pathogenesis of pancreatic disorders.

Eosinophils comprise approximately 1-4% of total blood leukocytes that reside in the intestine, bone marrow, mammary gland, and adipose tissues to maintain innate immunity in healthy individuals. Eosinophils have four toxic granules known as major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin (EDN), and upon degranulation, these granules promote pathogenesis of inflammatory diseases like allergy, asthma, dermatitis, and gastrointestinal disorders. Additionally, the role of eosinophils is underscored in exocrine disorders including pancreatitis.

Tacrolimus (FK506) treatment protects allergen-, IL-5- and IL-13-induced mucosal eosinophilia.

Eosinophils are a common clinical feature associated with chronic allergic diseases, and elemental diets, systemic steroids, anti-IL-5 and anti-IL-13 treatment have shown some therapeutic promise. Herein, we present evidence that pre- and post-intraperitoneal administration of tacrolimus (FK506) is very effective in reducing CCR3/Siglec-F eosinophils in Aspergillus-challenged asthma and EoE, CD2-IL-5 induced global eosinophilia, and DOX regulated IL-13-induced asthma. We used flow cytometry and anti-major basic protein (MBP) immunostaining to examine eosinophils in the spleen, bone marrow, BALF, lung, oesophagus and intestine.

Experimental Modeling of Eosinophil-Associated Diseases.

Eosinophils are an important subtype of leukocytes derived from bone marrow multipotent hematopoietic stem cells and represent about 1% of leukocytes in circulating blood. In homeostatic conditions, eosinophils reside in the intestine to maintain the balance of immune responses by communicating with gut microbes without causing inflammation. However, under the stressed or diseased condition, eosinophils degranulate, releasing their granule-derived cytotoxic proteins that are involved in inflammatory responses.

IL-15 immunotherapy is a viable strategy for COVID-19.

Coronavirus disease 2019 (COVID-19) is a pulmonary inflammatory disease induced by a newly recognized coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection was detected for the first time in the city of Wuhan in China and spread all over the world at the beginning of 2020. Several millions of people have been infected with SARS-CoV-2, and almost 382,867 human deaths worldwide have been reported so far.

Theranostic Nanoparticles for Pancreatic Cancer Treatment.

Pancreatic cancer is one of the low vascular permeable tumors with a high mortality rate. The five-year survival period is ~5%. The field of drug delivery is at its pace in developing unique drug delivery carriers to treat high mortality rate cancers such as pancreatic cancer.

Chronic Pancreatitis and the Development of Pancreatic Cancer.

Pancreatitis is a fibro-inflammatory disorder of the pancreas that can occur acutely or chronically as a result of the activation of digestive enzymes that damage pancreatic cells, which promotes inflammation. Chronic pancreatitis with persistent fibro-inflammation of the pancreas progresses to pancreatic cancer, which is the fourth leading cause of cancer deaths across the globe. Pancreatic cancer involves cross-talk of inflammatory, proliferative, migratory, and fibrotic mechanisms.

Significance of Interleukin (IL)-15 in IgE associated eosinophilic Esophagitis (EoE).

Background And Aim: IgE-mediated immune responses contribute to the pathogenesis of eosinophilic esophagitis (EoE). Interleukin (IL)-4 is a well-established cytokine involved in B cell activation, immunoglobulin (Ig) E production and isotype class switching. Earlier reports indicated that IL-15, B cells and IgE are induced in EoE pathogenesis.

Possible novel non-invasive biomarker for inflammation mediated pancreatic malignancy.

Objectives: Pancreatic malignancy is a major public health problem worldwide and recent reports indicated that pancreatic cancer will be second most common cause of cancer-related deaths by the end of 2021. The cause of increasing death rate is due to the nonexistence of detection tools to early diagnose, poor prognosis, resistance to chemotherapy and also lack in understanding the mechanism of PDAC pathogenesis. Circulating tumor cells (CTCs) play a major role in metastatic step of intravasation and presence of these cells are strong prognostic marker for the progression of pancreatic malignancy in chronic pancreatitis (CP).

Synergy of Interleukin (IL)-5 and IL-18 in eosinophil mediated pathogenesis of allergic diseases.

Eosinophils are circulating granulocytes that have pleiotropic effects in response to inflammatory signals in the body. In response to allergens or pathogens, exposure eosinophils are recruited in various organs that execute pathological immune responses. IL-5 plays a key role in the differentiation, development, and survival of eosinophils.

Intestinal overexpression of IL-18 promotes eosinophils-mediated allergic disorders.

Baseline eosinophils reside in the gastrointestinal tract; however, in several allergic disorders, excessive eosinophils accumulate in the blood as well in the tissues. Recently, we showed in vitro that interleukin (IL)-18 matures and transforms IL-5-generated eosinophils into the pathogenic eosinophils that are detected in human allergic diseases. To examine the role of local induction of IL-18 in promoting eosinophil-associated intestinal disorders, we generated enterocyte IL-18-overexpressing mice using the rat intestinal fatty acid-binding promoter (Fabpi) and analysed tissue IL-18 overexpression and eosinophilia by performing real-time polymerase chain reaction, Enzyme-Linked Immunosorbent Assay and anti-major basic protein immunostaining.

Attenuation of Allergen-, IL-13-, and TGF-α-induced Lung Fibrosis after the Treatment of rIL-15 in Mice.

Endogenous IL-15 deficiency promotes lung fibrosis; therefore, we examined the effect of induced IL-15 in restricting the progression of lung fibrosis. Our objective in this work was to establish a novel therapeutic molecule for pulmonary fibrosis. Western blot, qPCR, and ELISA were performed on the lung tissues of IL-15-deficient mice, and recombinant IL-15 (rIL-15)-treated CC10-IL-13 and CC10-TGF-α mice, and allergen-challenged CC10-IL-15 mice were examined to establish the antifibrotic effect of IL-15 in lung fibrosis.

Interleukin-18 has an Important Role in Differentiation and Maturation of Mucosal Mast Cells.

A significant amount of correlational evidence has linked increased levels of IL-18 with allergic diseases in both human and animal models, and, as mast cells are major mediators of allergies, we hypothesized that IL-18 may have a role in mast cell biology. Rationale for our hypothesis is based on the evidence that IL-3 deficient mice are not devoid of mast cells, even though IL-3 is a major differentiation and growth factor for mast cells. Accordingly, we cultured IL-18 responsive bone marrow CD34+ cells under a variety of conditions and cytokine combinations to examine mast cell differentiation and maturation using flow cytometry, quantitative PCR,and immunostaining techniques.

Chemical composition, antioxidant potential, macromolecule damage and neuroprotective activity of .

Herbal medicines are known to mitigate radical induced cell damage. Hence identification and scientific validation of herbal medicines contribute to better use in Ayurvedic/Unani research. In the present study, we investigated antioxidant and anti-apoptotic properties of ().