The role of bidirectional communication between the adipokines and the endogenous opioid system in an experimental mouse model of colitis-associated colorectal cancer.

Background: Colorectal cancer (CRC) is one of the leading causes of death globally. Multiple factors may contribute to the pathogenesis of CRC, including the abnormalities in the functioning of the endogenous opioid system (EOS) or adiponectin-related signaling. The aim of our study was to evaluate if differences in the expression of opioid receptors (ORs) influence the development of CRC and if modulation of adiponectin receptors using AdipoRon, a selective AdipoR1 receptor agonist, affects colorectal carcinogenesis.

Regulators of G-Protein Signaling (RGS) in Sporadic and Colitis-Associated Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common neoplasms worldwide. Among the risk factors of CRC, inflammatory bowel disease (IBD) is one of the most important ones leading to the development of colitis-associated CRC (CAC). G-protein coupled receptors (GPCR) are transmembrane receptors that orchestrate a multitude of signaling cascades in response to external stimuli.

Empagliflozin attenuates intestinal inflammation through suppression of nitric oxide synthesis and myeloperoxidase activity in in vitro and in vivo models of colitis.

Inflammatory bowel diseases (IBD) are characterized by chronic and relapsing inflammation affecting the gastrointestinal (GI) tract. The incidence and prevalence of IBD are relatively high and still increasing. Additionally, current therapeutic strategies for IBD are not optimal.

Pharmacological approaches to treat intestinal pain.

Introduction: Pain is one of the most substantial factors responsible for lowering quality of life in patients with intestinal diseases. Its multifactorial pathogenesis makes intestinal pain difficult to manage with currently available medications, especially considering the risk of serious adverse effects and exacerbation of underlying disease.

Areas Covered: The most commonly administered drugs in intestinal pain are medications forming the so-called analgesic ladder, which act directly on pain sensation: acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), and opioids in full range of activity strength.

The Involvement of the Endogenous Opioid System in the Gastrointestinal Aging in Mice and Humans.

Nearly 20% of elderly patients suffer from constipation, but the age-related changes in the gastrointestinal (GI) tract remain insufficiently elucidated. In this study, the alterations within the endogenous opioid system (EOS) as a potential cause of constipation in the elderly were evaluated. The GI functions were assessed in vitro and in vivo and compared between 6-, 12- and 18-month old mice.

The Anti-Inflammatory Effect of Acidic Mammalian Chitinase Inhibitor OAT-177 in DSS-Induced Mouse Model of Colitis.

Inflammatory bowel diseases (IBD) are chronic and relapsing gastrointestinal disorders, where a significant proportion of patients are unresponsive or lose response to traditional and currently used therapies. In the current study, we propose a new concept for anti-inflammatory treatment based on a selective acidic mammalian chitinase (AMCase) inhibitor. The functions of chitinases remain unclear, but they have been shown to be implicated in the pathology of various inflammatory disorders regarding the lung (asthma, idiopathic pulmonary fibrosis) and gastrointestinal tract (IBD and colon cancer).

[NLRP3 inflammasome as causative and protecting factor in pathogenesis of inflammatory bowel diseases].

Inflammatory bowel diseases (IBD) are a group of chronic and globally appearing conditions that significantly decrease patientsâ quality of life. The main representatives of IBD are Crohnâs disease and ulcerative colitis. Although the etiology of IBD is still not fully understood, the NLRP3 inflammasome is one of the most promising targets of research in this field.

Critical interactions between opioid and cannabinoid receptors during tolerance and physical dependence development to opioids in the murine gastrointestinal tract: proof of concept.

Introduction: Tolerance (TOL) and physical dependence (PD) constitute important limitations of opioid therapy. The aim of our study was to validate research tools to investigate TOL and PD and to characterize the interactions between opioid (OR) and cannabinoid (CB) receptors in these processes in the GI tract.

Methods: TOL was assessed through the comparison of morphine ability to inhibit electrically evoked smooth muscles contractility in the mouse ileum that was previously incubated with/without morphine for 1 h.

New insights into molecular pathways in colorectal cancer: Adiponectin, interleukin-6 and opioid signaling.

Colorectal cancer (CRC) is one of the most common cause of death among neoplasms around the world. The environmental factors, like diet and obesity, are crucial in CRC pathogenesis by creating cancer-favorable microenvironment and hormonal changes. Adiponectin, the adipose tissue-specific hormone, is generally considered to negatively correlate with CRC development.

The Nrf2 in the pathophysiology of the intestine: Molecular mechanisms and therapeutic implications for inflammatory bowel diseases.

Nrf2 (nuclear factor erythroid 2-related factor 2) is a stress-responsive transcription factor, associated with cellular homeostasis. Under normal conditions Nrf2 is kept in the cytoplasm by Kelch-like ECH-associated protein 1 (Keap1) which facilitates its degradation. Meanwhile, oxidative or electrophilic stress trigger Keap1 dissociation from the Nrf2/Keap1 complex and Nrf2 translocation to the nucleus where it induces the expression of numerous anti-oxidative and anti-inflammatory genes.