Endoplasmic Reticular Stress and Pathogenesis of Experimental Colitis: Mechanism of Action of 5-Amino Salicylic Acid.

Objectives: Inflammatory bowel diseases which are characterized by endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) signaling pathway are commonly treated with 5-amino salicylic acid (5-ASA). The objective of this study was to investigate the role of 5-amino salicylic acid in the UPR-signaling pathway in experimental colitis.

Materials And Methods: Colitis was induced in male Sprague-Dawley rats by intrarectal instillation of trinitrobenzene sulfonic acid.

The Role of Claudins in the Pathogenesis of Dextran Sulfate Sodium-Induced Experimental Colitis: The Effects of Nobiletin.

Background: The pathogenesis of inflammatory bowel diseases such as ulcerative colitis and Crohn's disease is not well understood. This study investigated the roles and regulation of the claudin-1, -2, -3, and -4 isoforms in the pathogenesis of ulcerative colitis, and the potential therapeutic effects of nobiletin.

Methods: Colitis was induced in rats by administering dextran sulfate sodium [DSS] in drinking water for seven days.

Upregulation of NADPH-oxidase, inducible nitric oxide synthase and apoptosis in the hippocampus following impaired insulin signaling in the rats: Development of sporadic Alzheimer's disease.

NADPH-oxidase (NOX) is a multi-subunit enzyme complex. The upregulation of NOX causes massive production of superoxide (O), which avidly reacts with nitric oxide (NO) and increases cellular reactive oxygen/nitrogen species (ROS/RNS). Increased ROS/RNS plays pivotal role in the sporadic Alzheimer's disease (sAD) development and brain damage following impaired insulin signaling.

Serotonergic and Adrenergic Neuroreceptor Manipulation Ameliorates Core Symptoms of ADHD through Modulating Dopaminergic Receptors in Spontaneously Hypertensive Rats.

The core symptoms of attention deficit hyperactivity disorder (ADHD) are due to the hypofunction of the brain's adrenergic (NE) and dopamine (DA) systems. Drugs that enhance DA and NE neurotransmission in the brain by blocking their transporters or receptors are the current therapeutic strategies. Of late, the emerging results point out the serotonergic (5-HT) system, which indirectly modulates the DA activity in reducing the core symptoms of ADHD.

Insights into early pathogenesis of sporadic Alzheimer's disease: role of oxidative stress and loss of synaptic proteins.

Oxidative stress, induced by impaired insulin signaling in the brain contributes to cognitive loss in sporadic Alzheimer's disease (sAD). This study evaluated early hippocampal oxidative stress, pre- and post-synaptic proteins in intraperitoneal (IP) and intracerebroventricular (ICV) streptozotocin (STZ) models of impaired insulin signaling. Adult male Wistar rats were injected with STZ, IP, or ICV, and sacrificed 1-, 3-, or 6-weeks post injection.

N-Acetylcysteine Amide against Aβ-Induced Alzheimer's-like Pathology in Rats.

Oxidative stress with a depletion of glutathione is a key factor in the initiation and progression of Alzheimer's disease (AD). N-Acetylcysteine (NAC), a glutathione precursor, provides neuroprotective effects in AD animal models. Its amide form, N-Acetylcysteine amide (NACA), has an extended bioavailability compared to NAC.

The impact of heat therapy on neuromuscular function and muscle atrophy in diabetic rats.

Diabetes Mellitus (DM) is the most common metabolic disease worldwide and is associated with many systemic complications. Muscle atrophy is one of the significant complications in DM patients, making routine tasks laborious as atrophy continues. It is known that heat stress stimulates heat shock proteins and other proteins that maintain muscle mass; however, it is not thoroughly studied in diabetic conditions.

Neuroprotective potential of ocimum sanctum (Linn) leaf extract in preventing and attenuating stress induced substantia nigral neuronal damage in rats.

Background: In Ayurveda; an Indian system of traditional medicine, Ocimum sanctum is said to have remedial effect on hriddaurbalya (problems affecting the mind), aakshepayukta vikara (nervous disorders) and shiroroga (diseases of head). Hence, in Ayurvedic practice, it is profoundly used as an antistress medicine. Stress is known to affect neurons of functionally significant brain regions like substantia nigra.

Early time course of oxidative stress in hippocampal synaptosomes and cognitive loss following impaired insulin signaling in rats: Development of sporadic Alzheimer's disease.

Oxidative stress, caused by impaired insulin signaling, plays a pivotal role in the pathogenesis of sporadic Alzheimer's disease (sAD). We investigated the oxidative stress parameters in the synaptosomes prepared from the hippocampus tissue in order to identify their potential role in sAD development in intraperitoneal (IP) and intracerebroventricular (ICV) streptozotocin (STZ) injections models of insulin signaling impairment. Rats were harvested 1, 3, or 6 weeks post treatment.

Impaired spatial navigation and age-dependent hippocampal synaptic dysfunction are associated with chronic inflammatory response in db/db mice.

Type 2 diabetes mellitus (T2DM) increases the risk of developing Alzheimer's disease (AD), which has been proposed to be driven by an abnormal neuroinflammatory response affecting cognitive function. However, the impact of T2DM on hippocampal function and synaptic integrity during aging has not been investigated. Here, we investigated the effects of aging in T2DM on AD-like pathology using the leptin receptor-deficient db/db mouse model of T2DM.

Anti-allergic, anti-asthmatic and anti-inflammatory effects of an oxazolidinone hydroxamic acid derivative (PH-251) - A novel dual inhibitor of 5-lipoxygenase and mast cell degranulation.

We have recently reported the discovery of a series of oxazolidinone hydroxamic acid derivatives that are potent inhibitors of 5-lipoxygenase (5-LO) [arachidonate 5-lipoxygenase; EC 1.13.11.

Tumor necrosis factor (TNF) induces astrogliosis, microgliosis and promotes survival of cortical neurons.

Objectives: Neuro-inflammation occurs as a sequence of brain injury and is associated with production of cytokines. Cytokines can modulate the function and survival of neurons, microglia and astrocytes. The objective of this study is to examine the effect of TNF on the neurons, microglia and astrocytes in normal brain and stab wound brain injury.

Prostaglandin E sensitizes the cough reflex centrally via EP3 receptor-dependent activation of NaV 1.8 channels.

Background: Cough hypersensitivity is a major characteristic feature associated with several types of cough, including chronic cough, but its underlying mechanisms remain to be fully understood. Inflammatory mediators, such as prostaglandin E (PGE), have been implicated in both peripheral induction and sensitization of the cough reflex. In this study, using a conscious guinea pig model of cough, we investigated whether PGE can sensitize the cough reflex via central actions and, if so, via which mechanisms.

Prevalence of lead toxicity in adolescents in Kuwait.

Background: Elevated blood lead level (EBLL) is a public health problem in both developing and industrialized countries. Being a petrochemical-based economy, lead (Pb) levels are expected to be high in Kuwait, but systematic data on population exposure are lacking. This study aimed at determining the prevalence of EBLL in adolescents in Kuwait.

Association of blood lead level with vitamin D binding protein, total and free 25-hydroxyvitamin D levels in middle-school children.

A negative association between blood Pb level (BPbL) and vitamin D metabolites in occupationally exposed populations has been reported, but data from the general population are scarce. Furthermore, the association between BPbL and vitamin D binding protein (DBP) and free 25-hydroxyvitamin D (25(OH)D) has not been reported. We investigated the association of BPbL with DBP, total and free 25(OH)D in healthy adolescents (n 1347; age range 11-16 years) cross-sectionally selected from all Governorates of Kuwait, utilising multi-stage cluster random sampling.

Interferon-Gamma and Interleukin-1Beta Enhance the Secretion of Brain-Derived Neurotrophic Factor and Promotes the Survival of Cortical Neurons in Brain Injury.

Neuro-inflammation is associated with the production of cytokines, which influence neuronal and glial functions. Although the proinflammatory cytokines interferon-γ (IFN-γ) and interleukin-1Beta (IL-1β) are thought to be the major mediators of neuro-inflammation, their role in brain injury remains ill-defined. The objective of this study was to examine the effect of IFN-γ and IL-1β on survival of cortical neurons in stab wound injury in mice.

Low Doses of Thymoquinone and Ferulic Acid in Combination Effectively Inhibit Proliferation of Cultured MDA-MB 231 Breast Adenocarcinoma Cells.

Thymoquinone (TQ) and Ferulic Acid (FA) are natural ingredients from and , respectively. Individually both TQ and FA have shown anticancer properties in a variety of cancer cell lines. We investigated the combination effect of lower doses of TQ and FA on proliferation, apoptosis, and cell cycle of a breast cancer cell line MDA-MB 231.

dBcAMP Rescues the Neurons From Degeneration in Kainic Acid-Injured Hippocampus, Enhances Neurogenesis, Learning, and Memory.

Dibutyryl cyclic adenosine monophosphate (dBcAMP) is a cell-permeable synthetic analog of cyclic adenosine monophosphate (cAMP). Although the elevation of cAMP levels was reported to promote the functional recovery in spinal cord injury, its role in neurogenesis or functional recovery after hippocampal injury is unknown. The objective of the study was to investigate the effects of dBcAMP on learning, memory, and hippocampal neurogenesis in the excitotoxically lesioned hippocampus.

Effect of N-Acetyl Cysteine on Intracerebroventricular Colchicine Induced Cognitive Deficits, Beta Amyloid Pathology, and Glial Cells.

Among the many factors responsible for the cognitive decline in Alzheimer's disease, beta amyloid protein and plaque formation is crucial. This amyloid pathology is associated with activation of glial cells and oxidative stress but whether oxidative stress activates beta amyloid protein in the neurons is not clear. Further the expression of microglia is also known to vary during pathogenesis of beta amyloid plaques.

Memantine Is Protective against Cytotoxicity Caused by Lead and Quinolinic Acid in Cultured Rat Embryonic Hippocampal Cells.

Quinolinic acid (QA) is an excitotoxic metabolite of the kynurenine pathway of tryptophan metabolism produced in response to inflammation and oxidative stress. Lead (Pb) causes oxidative stress and thus may produce neurotoxicity by increasing QA production. We investigated the in vitro cytotoxic effects of Pb and QA and the protective effects of the NMDA receptor antagonist memantine.

-Acetyl Cysteine Supplement Minimize Tau Expression and Neuronal Loss in Animal Model of Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by the accumulation of neurofibrillary tangles (NFT), deposition of beta amyloid plaques, and consequent neuronal loss in the brain tissue. Oxidative stress to the neurons is often attributed to AD, but its link to NFT and β-amyloid protein (BAP) still remains unclear. In an animal model of AD, we boosted the oxidative defense by -Acetyl cysteine (NAC), a precursor of glutathione, a powerful antioxidant and free radical scavenger, to understand the link between oxidative stress and NFT.

Intraventricular infusion of quinolinic acid impairs spatial learning and memory in young rats: a novel mechanism of lead-induced neurotoxicity.

Background: Lead (Pb), a heavy metal, and quinolinic acid (QA), a metabolite of the kynurenine pathway of tryptophan metabolism, are known neurotoxicants. Both Pb and QA impair spatial learning and memory. Pb activates astrocytes and microglia, which in turn induce the synthesis of QA.

Dibutyryl Cyclic Adenosine Monophosphate Rescues the Neurons From Degeneration in Stab Wound and Excitotoxic Injury Models.

Dibutyryl cyclic adenosine monophosphate (dBcAMP), a cell-permeable synthetic analog of cAMP, has been shown to induce astrogliosis in culture. However, the exact mechanism underlying how dBcAMP exerts its function is not clear. The objective of this study was to examine the effects of dBcAMP on astrogliosis and survival of neurons in stab wound and kainic acid models of brain injury.

Exposure to low level of lead during preweaning period increases metallothionein-3 expression and dysregulates divalent cation levels in the brain of young rats.

Lead (Pb) is a neurotoxic heavy metal, but the mechanism of its neurotoxicity is not clearly understood. Expression of metallothioneins (MTs) is induced in response to heavy metal exposure as a protective mechanism against heavy metal toxicity. There are several isoforms of MTs (MT-1 to 4), of which MT-3 is the neuron specific isoform, which also has neurite growth inhibitory effects.

Monoamine oxidase-B inhibitor protects degenerating spinal neurons, enhances nerve regeneration and functional recovery in sciatic nerve crush injury model.

Monoamine oxidase-B (MAOB), a flavin adenine dinucleotide (FAD), is an enzyme which catalyzes the oxidation of amines. MAOB is proposed to play a major role in the pathogenesis of neurodegeneration through the production of reactive oxygen species (ROS) and neurotoxins. The present study was designed to outline the effects of the MAOB inhibitor (MAOB-I) on neuroprotection of spinal neurons, regeneration of sciatic nerve fibers, and recovery of sensory-motor functions in the sciatic nerve crush injury model.