Asthma is a complex, chronic inflammatory lung disease which is characterized by persistent airway inflammation and airway wall remodeling, that includes the structural changes in the airway wall, epithelial cell shedding, hyperplasia and hypertrophy of the ASM (airway smooth muscle) bundles, basement membrane thickening and increased vascular density. Airway wall remodeling starts early in the pathogenesis of asthma [Ref.1]. It originates from complex interactions between genetic factors and environmental agents such as aeroallergens and respiratory viruses [Ref.2]. In the airway lumen, TSLP, IL-25, and IL-33 acts directly on dendritic cells and then it processes the antigenic molecules and present them to Th0 (naïve T helper cells) [Ref.3]. Further, Th0 get[..]

Chronic obstructive pulmonary disease (COPD) is a major global health problem that is becoming preva¬lent, particularly in developing countries [Ref.1]. It is one of the most common diseases in the world, with a lifetime risk estimated to be as high as 25%, and now equally affects both men and women [Ref.2]. COPD is greatly under¬ diagnosed and often diagnosed late in its course, so there are vigorous attempts to increase awareness of this dis¬ease and to promote the use of spirometry to identify more patients [Ref.3]. COPD involves chronic inflammation of the periph-eral airways and lung parenchyma, which leads to pro¬gressive narrowing of the airways and shortness of breath [Ref.4.]Cigarette smoke (and other irritants) activates macrophages and[..]

Cancer cell genotypes are a manifestation of six essential alterations in cell physiology that collectively dictate malignant growth; self-sufficiency in growth signals, insensitivity to growth-inhibitory (anti-growth) signals, evasion of programmed cell death (apoptosis), limitless replicative potential, sustained angiogenesis and tissue invasion and metastasis. Environmental and endogenous DNA-damaging agents and genetic instability drive tumor progression by generating mutations in two types of genes, oncogenes and tumor suppressor genes, providing cancer cells with selective growth advantage and thereby leading to the clonal outgrowth of a tumor. In general, oncogenes (called proto-oncogenes in their normal, non-mutated form) promote cell proliferation and[..]

The MAPK (Mitogen-Activated Protein Kinase) pathway is one of the primordial signaling systems that nature has used in several permutations to accomplish an amazing variety of tasks. It exists in all eukaryotes, and controls such fundamental cellular processes as Proliferation, Differentiation, Survival and Apoptosis. Mammalian MAPK can be divided into four groups based on their structure and function: ERKs (Extracellular signal-Regulated Kinases), p38MAPKs, JNKs (c-Jun NH2-terminal Kinases) and ERK5 (Extracellular signal-Regulated Kinase-5) or BMK. Activation of these MAPKs occurs through a cascade of upstream kinases; a MAPKKK (MAPK Kinase Kinase) first phosphorylates a dual-specificity protein kinase MAPKK (MAPK Kinase), which in turn phosphorylates the MAPK. This[..]

Malaria is the world's largest parasitic disease, killing more people than any other communicable disease except Tuberculosis. Malaria is a major public health problem in more than 100 countries, inhabited by a total of some 2.4 billion people, or close to half of the world's population. Each year, 300–500 million people contract malaria and about 3 million die, most of which are children under five years old. In absolute numbers, malaria kills 3,000 children per day under the age of five. The total number of deaths readily exceeds that from AIDS. Human malaria is caused by infection with intracellular protozoan parasites of the genus Plasmodium that are transmitted by Anopheles mosquitoes. Four species of Plasmodium infect humans: P. falciparum, P.[..]

Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders affecting humans and animals. Human TSEs are often categorized with other protein misfolding neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease, Huntington’s disease, fronto-temporal dementia and amyotrophic lateral sclerosis. The mechanism of disease propagation is well understood and involves the conformational conversion of a normal cell-surface protein (PrPc) into a protease-resistant, Beta-sheet-rich form (PrPSc) that is infectious in the absence of nucleic acid. However, some forms of spongiform encephalopathies are commonly associated with inherited mutations at the PrPc coding gene (PrnP), particularly[..]

Human eosinophils are crucial effector cells implicated in a number of chronic inflammatory reactions, associated with bronchial asthma, allergic-inflammatory diseases, and parasitic infections.The chemotactic response of eosinophils is mostly mediated by CCR3 (CC Chemokine Receptor-3), a member of the G protein-coupled, seven-transmembrane receptor family, linked to heterotrimeric G-Proteins. Although its expression was first thought to be limited to eosinophils, CCR3 is now known to be more widely expressed on cells involved in allergic inflammation, such as basophils, macrophages, mast cells, neutrophils, airway epithelial cells, and potentially TH2 T-lymphocytes . Chemokines such as: Eotaxin, Eotaxin2, and Eotaxin3 signal exclusively via CCR3 that recruit[..]

CDKN2A (Cyclin Dependent Kinase Inhibitor-2A), which is also referred to as p16(INK4A) encodes ARFs (Alternative Reading Frames), or transcript variants. In mice the p16(INK4A) encodes a transcript variant known as p19(ARF), whereas in humans it encodes p14(ARF).p19(ARF) is a key component of a major human tumor suppressor pathway that is responsible for arresting cell-cycle progression and inducing cell death in response to DNA damage and oncogenic stress. It plays an important role as an inhibitor of the MDM2-mediated degradation of p53. p19(ARF) activity is linked to its oligomerization and is sensitive to the redox status of the cell. Oxidative stress affects p19(ARF) oligomerization. Tumor promotion is associated with an altered redox status, and it is known that[..]

PI3Ks (Phosphoinositide-3 Kinases) are heterodimeric lipid kinases that are composed of a regulatory and catalytic subunit that are encoded by different genes. The phosphorylated lipid phosphatidylinositol 3-phosphate (PtdIns3P) is an important signaling molecule and has been found to localize to endosomes, multivesicular bodies, phagosomes, midbodies, peroxisomes and omegasomes. The generated PtdIns3P attracts PtdIns3P-binding factors, which either contain a PX (Phox homology) domain or a FYVE (Fab1p, YOTB, Vac1p and EEA1) domain. The subsequent signaling cascades are involved in endocytic transport and endocytic signaling, cytokinesis as well as autophagy. (Ref.1). Two distinct VPS34P (Vacuolar Protein-Sorting-34-PI3K (Phosphatidylinositde-3 Kinase)) complexes occur[..]

cAMP (Cyclic Adenosine 3',5'-monophosphate) is the first identified second messenger, which has a fundamental role in the cellular response to many extracellular stimuli. The cAMP signaling pathway controls a diverse range of cellular processes. Indeed, not only did cAMP provide the paradigm for the second messenger concept, but also provided the paradigm for signaling compartmentalization. The different receptors, chiefly the GPCRs (G-Protein Coupled Receptors), Alpha and Beta-ADRs (Adrenergic Receptors), Growth Factor receptors, CRHR (Corticotropin Releasing Hormone Receptor), GcgR (Glucagon Receptor), DCC (Deleted in Colorectal Carcinoma), etc are responsible for cAMP accumulation in cells that cause different physiological outcomes, and changes in cAMP[..]

Bacterial meningitis is an inflammation of the meninges, in particular the arachnoid and the pia mater, associated with the invasion of bacteria into the subarachnoid space.The pathogens take advantage of the specific features of the immune system in the CNS, replicate and induce inflammation. A hallmark of bacterial meningitis is the recruitment of highly activated leukocytes into the CSF.The predominant causative pathogens in adults are Streptococcuspneumoniae, Neisseriameningitidis, and Listeria monocytogenes which are responsible for about 80% of all cases, while GBS(group B Streptococcus), S. pneumoniae, Escherichiacoli,N.meningitidis, and Haemophilusinfluenza type B cause about 90% of cases of BM in children globally.The mortality rate of neonatal meningitis was[..]

Small interfering RNAs (siRNAs) are 21–23nt dsRNA (double-stranded RNA) molecules that facilitate potent and sequence-specific gene suppression via the mechanism of RNAi (RNA interference). When introduced into cultured mammalian cells, siRNAs facilitate the degradation of mRNA sequences to which they are homologous, thereby silencing the encoding gene. The basic mechanism behind RNAi is the breaking of a dsRNA matching a specific gene sequence into short pieces of siRNA. These siRNAs with symmetric 2–3nt 3' overhangs and 5'-phosphate and 3'-hydroxyl groups post-transcriptionally silences a gene through mRNA inhibition or degradation. Interference of gene expression by siRNA is now recognized as a naturally occurring biological strategy for[..]