The gastrointestinal (GI) tract plays a central role in maintaining immune homeostasis, i.e., tolerance to non-pathogenic commensal bacteria, self-antigens, and food antigens, while also protecting the host against pathogenic organisms by mounting an inflammatory response. The fine line between tolerance and inflammation of the GI immune system, when disrupted, may result in diseases such as inflammatory bowel disease (IBD). IBD is a chronic inflammatory disorder of the GI tract, it is defined into two major subtypes, Crohn’s disease (CD) and ulcerative colitis (UC) (Ref. 1 & 2).The overactive mucosal immune response against gut microorganisms in genetically susceptible individuals is thought to have major impact in the development and pathophysiology of IBD.[..]

Chronic lymphocytic leukemia (CLL) is a type of cancer of the blood and bone marrow in which the bone marrow makes too many lymphocytes. This is a type of slow-growing leukaemia that affects developing B-lymphocytes. CLL is a malignancy of mature CD5+ B-cells that is characterized by apoptosis resistance and dysfunctional immune system. Within a complex cellular network in bone marrow and secondary lymphoid organs (SLOs), T-cells represent a key cell type in the CLL microenvironment that considerably expands along with disease course. In people with CLL, lymphocytes undergo a malignant (cancerous) change and become leukaemic cells. CLL remains stable for many months and years and has little, impact on their lifestyle or general health. Around 30-50% of people diagnosed[..]

Chronic lymphocytic leukemia (CLL) is a type of cancer of the blood and bone marrow in which the bone marrow makes too many lymphocytes. This is a prototypic malignancy that not only depends on intrinsic genetic defects, but also depends on the interactions with cells present in microenvironment such as T cells, monocyte-derived cells (MDC), and stromal cells (such as endothelial cells, fibroblastic reticular cells, and pericytes). Signals emanating from the microenvironment plays a significant role in supporting CLL cell proliferation and survival, as well as facilitating chemoresistance, cell proliferation, and migration. Tissue stromal cells, such as stromal cells and monocytederived nurselike cells (NLC) are critical elements of the tissue microenvironment in CLL,[..]

The immune response is initiated by innate immunity following exposure to foreign substances or tissue injury. Innate immunity exerts protective roles in host homeostasis in part by priming adaptive immune responses against persisting insults and inducing inflammation. However, the unbalanced immune response leads to severe inflammation and uncontrolled tissue damage and disease. Sensing of the intestinal microbiota by the host mucosal immune system plays significant roles in maintaining intestinal homeostasis and inducing systemic protective responses. Thus, manipulation of the intestinal microbiota is a potential alternative approach for maintaining health and preventing and/or treating diseases. Probiotics were defined as ‘live microorganisms which, when[..]

Probiotics are living microorganisms that confer health benefits to the host when administered in adequate amounts; however, dead bacteria and their components also exhibit probiotic properties. Bifidobacterium and strains of lactic acid bacteria are the most widely used bacteria that exhibit probiotic properties and are included in many functional foods and dietary supplements (Ref.1&2).During intestinal bacterial infection, there is colonization of the gut epithelium by the pathogen. The mucus produced by goblet cells accounts as one of the first lines of defense against pathogenic bacteria colonization and the intestinal cells produce antimicrobial peptides (cathelicidins and defensins) in order to contain the infection. Cathelicidins are small, cationic,[..]

Endocannabinoids are endogenous ligands of cannabinoid receptors that bind as the principal biologically active component of Cannabis sativa, D9-tetrahydrocannabinol (D9-THC), and also comprise amides, esters and ethers of long chain polyunsaturated fatty acids. Endogenous cannabinoids (endocannabinoids) serve as retrograde messengers at synapses in various regions of the brain. The endocannabinoid system (ECS) is a neuromodulatory system that plays important role in central nervous system (CNS) development, synaptic plasticity and in cancer pathogenesis as tumor promoters. The endocannabinoid system consists of endocannabinoids (major derivative include arachydonoyl ethanolamide (anandamide, AEA) and 2-arachydonoil glycerol (2AG)), their G-protein-coupled receptors[..]

CHREBP (Carbohydrate-response element-binding protein) is the major transcription factor conferring glucose-induced gene expression in pancreatic islets, liver and adipose tissue. To date, only two natural isoforms, CHREBPα and CHREBPβ, have been identified. CHREBP-β was identified in adipose tissue and found to be also expressed in islets and involved in glucose-induced beta cell proliferation. In adult pancreatic β cells, CHREBP activity is regulated by its cytosolic/nuclear localization (Ref.1&2).Chronic hyperglycemia, the hallmark of type 1 and T2D, can cause damage to numerous cell types, including pancreatic β cells. Although under physiological conditions an increase in glucose metabolism stimulates insulin secretion,[..]

Coronavirus disease 2019 (COVID-19) is a pandemic respiratory disease caused by the SARS-CoV-2 coronavirus that is rapidly evolving and spreading at a different rate in different countries. SARS-CoV-2 causing COVID-19, a kind of viral pneumonia with an unusual outbreak in Wuhan, China, in December 2019, belongs to the beta-coronavirus group of the Coronaviridae family, order Nidovirale, which also include other deadly viruses like SARS and MERS. SARS-CoV-2 shows about 88 percent identity to two bat-derived sequence of severe acute respiratory syndromes (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, and about 50 percent identity to the sequence of MERS-CoV (Ref.1 and 2). The SARS-CoV-2 genome consists of a positive sense single stranded RNA molecule[..]

Ethanol is a psychoactive substance with rewarding and sedative-hypnotic properties that stem largely from its acute effects on specific signaling proteins that lead to changes in localization and post-translational modifications, gene expression and neuronal excitability. Neurons adapt to repeated ethanol exposure through homeostatic changes in cellular signaling pathways that serve to maintain nervous system function in the presence of ethanol. The STOP and GO intracellular signaling pathways control alcohol drinking behavior. Moderate and/or limited consumption of alcohol results in the activation of signaling cascades within the STOP pathways. STOP signaling pathways which center on genes such as BDNF and GDNF. Activation of the STOP signaling cascades limits the[..]

GVHD (Graft-Versus-Host Disease) is the main complication after allogeneic SCT (Stem Cell Transplantation) and induced by donor T cells in the graft. As in physiological T cell responses, alloreactive T cells depend on their activation by APCs (Antigen Presenting Cells). Potential APCs are B cells, monocytes/macrophages,and mainly dendritic cells (DC), the most efficient cells in antigen uptake, processing, and presentation on HLA class I and class II molecules. In HLA-mismatched SCT, HLA molecules are recognized directly by donor T cells with a variable contribution of the HLA-bound peptide, whereas mHA (Minor Histocompatibility Antigens) are the main targets in HLA-identical SCT. These mHA consist of HLA-bound peptides derived from polymorphic proteins that differ[..]

T-cell activation and effector function is mediated by the formation of a long-lasting interaction established between T-cells and APCs (Antigen-Presenting Cells) called Immunological synapse (IS). During T-cell activation, different signaling molecules as well as the cytoskeleton and the endosomal compartment are polarized to the IS. Compartmentalization of interactions at the interface of T and B cells as the central accumulation of T-cell receptor–major histocompatibility complex–peptide (TCR-MHCp) interactions surrounded by a peripheral ring of adhesion molecule interactions. They called these zones, c-SMAC or p-SMAC respectively (central and peripheral supra-molecular activation clusters). The major components of the c-SMAC are key molecules for T[..]

Cushing’s syndrome (CS) has been described for about a century and represents a classical syndrome in endocrinology. Recent years have been marked by progress in elucidating the etiology and the pathogenesis of the disease. Endogenous Cushing’s syndrome is classically divided into corticotrophin (ACTH)-dependent and ACTH-independent hypercortisolism. ACTH-dependent subtype is caused by a pituitary ACTH-producing adenoma, also known as Cushing’s disease (70% of endogenous Cushing’s syndrome). Other cases are caused by ectopic ACTH secretion (10%) from a variety of neuroendocrine neoplasms including para ganglioma,phaeochromocytoma and neuroendocrine tumours of various sites (lung, thyroid, thymus,appendix and pancreas. While ACTH dependent[..]