Effect of TLRs and nuclear PPARγ receptors on the mechanisms of intestinal carcinogenesis.

Tool Like Receptors (TLR) are transmembrane proteins that play an important role in immune reactions associated with the recognition of pathogenic factors that cause infection. However, chronic inflammatory conditions associated with the activation of these receptors create favorable conditions for the development of cancerous processes. The relationship between nuclear PPARγ receptors and TLR receptors is also important, whose role and importance in the process of carcinogenesis is the subject of various studies.

Recent Advances in the Gastric Mucosal Protection Against Stress-induced Gastric Lesions. Importance of Renin-angiotensin Vasoactive Metabolites, Gaseous Mediators and Appetite Peptides.

Stress is known to cause severe adverse effects in the human gastrointestinal tract including mucosal microbleedings and erosions or even gastric ulceration but the mechanism of these complications has not been fully elucidated. The pathogenesis of stress-induced gastric damage involves the fall in Gastric Blood Flow (GBF), an increase in gastric acid secretion and gastric motility, enhanced adrenergic and cholinergic nerve activity and the rise in gastric mucosal generation of reactive oxygen species. The gastric mucosal defense mechanisms against the deleterious effect of stress include the activation of the hypothalamic-pituitary-adrenal axis which has been linked with glucocorticoids release capable of counteracting of stress-induced gastric lesions.

Terapeutic importance of apoptosis pathways in pancreatic cancer.

Recent studies indicate the significant role of apoptosis and the genes that control it in the process of carcinogenesis. Apoptosis or programmed cell death is a complex process that controls cell proliferation and maintenance of accounting for the necessary balance in the body. Disturbances of apoptotic signalling pathways directly lead to the development and progression of cancer.

The renin-angiotensin system and its vasoactive metabolite angiotensin-(1-7) in the mechanism of the healing of preexisting gastric ulcers. The involvement of Mas receptors, nitric oxide, prostaglandins and proinflammatory cytokines.

The inhibition of angiotensin-converting enzyme (ACE) or the blockade of angiotensin (Ang) AT-1 receptors affords protection against acute gastric mucosal injury, but whether the major metabolite of renin-angiotensin system (RAS), Ang-(1-7), accelerates the healing process of preexisting gastric ulcers remains unknown. Previous studies documented that Ang-(1-7) acting via its own Mas receptor exerts vascular responses opposing those of Ang II. We studied the effects of the Ang-(1-7)/Mas receptor axis on the healing rate of acetic-acid-induced gastric ulcers with or without the blockade of Mas receptors by A 779 and compared it with the effects of activation and blockade of the AT-1 receptor by the treatment with Ang II and losartan, respectively, the inhibition of ACE by lisinopril, the NO/cNOS inhibition by L-NAME and inhibition of prostaglandin/COX system by indomethacin in the presence of Ang-(1-7).

Esophagoprotective activity of angiotensin-(1-7) in experimental model of acute reflux esophagitis. Evidence for the role of nitric oxide, sensory nerves, hypoxia-inducible factor-1alpha and proinflammatory cytokines.

Gastroesophageal reflux disease (GERD) is a global disease rapidly increasing among world population. The pathogenesis of reflux esophagitis which is considered as the early stage of GERD is complex, resulting from an imbalance between aggressive factors damaging the esophagus and a number of the natural defense mechanisms. The esophageal mucosa is in a state of continuous exposure to potentially damaging endogenous and exogenous factors.

Lipid peroxidation, reactive oxygen species and antioxidative factors in the pathogenesis of gastric mucosal lesions and mechanism of protection against oxidative stress - induced gastric injury.

The gastric mucosa plays an important role in the physiological function of the stomach. This mucosa acts as gastric barrier, which protects deeper located cells against the detrimental action of the gastric secretory components, such as acid and pepsin. Integrity of the gastric mucosa depends upon a variety of factors, such as maintenance of microcirculation, mucus-alkaline secretion and activity of the antioxidizing factors.

Involvement of cyclooxygenase-1 and cyclooxygenase-2 activity in the therapeutic effect of ghrelin in the course of ethanol-induced gastric ulcers in rats.

Previous studies have shown that treatment with ghrelin exhibits protective and therapeutic effects in the gut. Aim of our present investigation was to examine the influence of ghrelin administration on the healing of ethanol-induced gastric ulcers and determine the role of cyclooxygenase-1 and cyclooxygenase-2 in this effect. Our studies were performed on male Wistar rats.

Experimental healing of preexisting gastric ulcers induced by hormones controlling food intake ghrelin, orexin-A and nesfatin-1 is impaired under diabetic conditions. A key to understanding the diabetic gastropathy?

Hormonal peptides like ghrelin, orexin A (OXA) or nesfatin-1 not only regulate appetite, which is their basic biological function, but also contribute to mechanisms responsible for maintaining integrity of the gastric mucosa. Previous studies including those from our laboratory have revealed that their gastroprotective effect results from cooperation with other factors responsible for protection of the gastric mucosa, including prostaglandin (PG) synthesis pathway, nitric oxide (NO) and the sensory afferent fibres releasing the vasoactive neurotransmitters. The aim of the present study was to determine whether ghrelin, orexin-A (OX-A) or nesfatin-1 with their protective effect on the gastric mucosa, also can modify the healing of chronic gastric ulcers.

Mechanisms of esophageal protection, gastroprotection and ulcer healing by melatonin. implications for the therapeutic use of melatonin in gastroesophageal reflux disease (GERD) and peptic ulcer disease.

Melatonin is a potent reactive oxygen metabolite scavenger and antioxidant that has been shown to influence many physiological functions of the gastrointestinal (GI) tract including secretion, motility, digestion and absorption of nutrients. The role of melatonin in gastroduodenal defense and ulcer healing has been the subject of recent investigations. Melatonin produced in the GI mucosa plays an important role in protection against noxious agents thus contributing to the maintenance of GI integrity and to esophageal protection, gastroprotection and ulcer healing.

New satiety hormone nesfatin-1 protects gastric mucosa against stress-induced injury: mechanistic roles of prostaglandins, nitric oxide, sensory nerves and vanilloid receptors.

Nesfatin-1 belongs to a family of anorexigenic peptides, which are responsible for satiety and are identified in the neurons and endocrine cells within the gut. These peptides have been implicated in the control of food intake; however, very little is known concerning its contribution to gastric secretion and gastric mucosal integrity. In this study the effects of nesfatin-1 on gastric secretion and gastric lesions induced in rats by 3.

Probiotics in the mechanism of protection against gut inflammation and therapy of gastrointestinal disorders.

A growing body of experimental and clinical evidence supports the hypothesis that the intestinal microbiota markedly influences function and the structure of the mucosal lining. Intestinal microbiota can potentially cause damage to the mucosa either directly by releasing toxins or indirectly by causing a detrimental immune response. Probiotic bacteria have been defined as live microorganisms, which when consumed in adequate amounts, confer a health benefit for the host.

Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, interacts with gastric oxidative metabolism and enhances stress-induced gastric lesions.

Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthase known to exert vasoconstriction of vascular bed. The elevation of ADMA has been considered as the cardiovascular risk factor associated with hyperlipidemia, hypercholesterolemia and metabolic syndrome. ADMA is produced by the action of dimethylarginine dimethylaminohydrolase (DDAH), which hydrolyzes ADMA to L-citrulline and dimethylamine.

The impact of asymmetric dimethylarginine (ADAMA), the endogenous nitric oxide (NO) synthase inhibitor, to the pathogenesis of gastric mucosal damage.

This review was designed to provide an update on the role of asymmetric arginine (ADMA), the endogenous inhibitor of nitric oxide (NO) synthase in the pathophysiology of the upper gastrointestinal (GI) tract. Numerous studies in the past confirmed that NO is a multifunctional endogenous gas molecule involved in most of the body organs' functional and metabolic processes including the regulation of gastrointestinal (GI) secretory functions, motility, maintenance of GI integrity, gastroprotection and ulcer healing. NO is metabolized from L-arginine by enzymatic reaction in the presence of constitutive NO synthase.

Effects of peripherally and centrally applied ghrelin in the pathogenesis of ischemia-reperfusion induced injury of the small intestine.

Ghrelin is an important hormone involved in the control of the human appetite center. Recently, protective properties of this hormone have been recognized in various models of impairment of the gastric mucosa, including stress, ischemia and reperfusion (I/R). Ghrelin is predominantly secreted by the gastric mucosa of stomach, but there are other sources of ghrelin, for example in the hypothalamus and various parts of the central nervous system (CNS) that should be taken into consideration.

Antibiotic treatment with ampicillin accelerates the healing of colonic damage impaired by aspirin and coxib in the experimental colitis. Importance of intestinal bacteria, colonic microcirculation and proinflammatory cytokines.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for their anti-inflammatory, analgesic and antipyretic effects, however their use is associated with the broad spectrum of side effects observed in human as well as the experimental animals. Despite damaging activity of NSAIDs in upper gastrointestinal (GI) tract, these drugs exert deleterious influence in lower GI tract, including colon. The role of GI microflora in the pathogenesis of NSAIDs-induced experimental colonic damage is not completely understood.

Role of sensory nerves in gastroprotective effect of anandamide in rats.

Previous studies have shown that stimulation of cannabinoid 1 (CB1) receptor protects the gastric mucosa against stress-induced lesion. Aim of the present study was to examine the influence of anandamide on lipid peroxidation and antioxidant defense system in gastric mucosa and the role of sensory nerves in gastroprotective effects of cannabinoids. Studies were performed on rats with intact or ablated sensory nerves (by neurotoxic doses of capsaicin).

Nitric oxide (NO)-releasing aspirin and (NO) donors in protection of gastric mucosa against stress.

Acute gastric mucosal lesions represent an important clinical problem. The experimental model of acute gastritis such as water immersion restraint (WRS) stress is useful tool in examination of pathomechanism of acute gastric damage. Nitric oxide (NO) plays an important role in the maintenance of gastric barrier, however the role of reactive oxygen species (ROS) in the interaction between NO and gastric mucosa integrity has been little studied.

Helicobacter pylori inhibits expression of heat shock protein 70 (HSP70) in human epithelial cell line. Importance of Cag A protein.

Heat shock proteins (HSP) are crucial for the maintenance of cell integrity under normal cell growth and at pathophysiological conditions such as colonization of gastric mucosa by Helicobacter pylori (Hp). The effect of Hp on mRNA expression for HSP70 in the gastric epithelial cells in vitro has been little studied and remains inconclusive. In this study we attempted to determine the alterations in gene expression for HSP70 induced by two live strains of Hp in the epithelial MKN7 cells.