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Deprivation of sleep (DS) and its effects on circadian rhythm gene expression are not well understood despite their influence on various physiological and psychological processes. This study aimed to elucidate the changes in the expression of circadian rhythm genes following a night of sleep and DS. Their correlation with sleep architecture and physical activity was also examined. The study included 81 participants who underwent polysomnography (PSG) and DS with actigraphy. Blood samples were collected after PSG and DS. Expression levels of brain and muscle ARNT-like 1 (BMAL1), circadian locomotor output cycles kaput (CLOCK), neuronal PAS domain protein 2 (NPAS2), period 1 (PER1), cryptochrome 1 (CRY1) and nuclear receptor subfamily 1 group D member 1 (NR1D1) were analyzed using qRT-PCR. DS decreased the expression of CLOCK and BMAL1 while increasing PER1. PER1 expression correlated positively with total sleep time and non-rapid-eye-movement (NREM) sleep duration and negatively with sleep latency, alpha, beta and delta waves in the O1A2 lead. Physical activity during DS showed positive correlations with CLOCK, BMAL1, and CRY1. The findings highlight the role of PER1 in modulating sleep patterns, suggesting potential targets for managing sleep-related disorders. Further research is essential to deepen the understanding of these relationships and their implications.

The present work describes the protolytic properties of the sialorphin derivative (Pal-Lys- Lys-Gln-His-Asn-Pro-Arg) in an aqueous solution, at constant temperature 25.0 ± 0.1 °C and ionic strength 0.1 M (NaClO4), over the entire pH range. The overall protonation constants of the studied ligand were calculated by the potentiometric method. The logarithm values of the stepwise dissociation constants of the sialorphin derivative were found to be: [LH] = 11.88 ± 0.09, [LH2]+ = 9.96 ± 0.03, [LH3]2+ = 8.71 ± 0.03, [LH4]3+ = 5.49 ± 0.03, [LH5]4+ = 2.82 ± 0.03. The percentage of each species formed in an aqueous solution was estimated from the species distribution curves as a function of pH (82% [LH] at pH 11.0, 68% [LH2]+ at pH 9.3, 95% [LH3]2+ at pH 7.1, 90% [LH4]3+ at pH 4.2, 85% [LH5]4+ at pH  2.0). The five protonation constants indicate that the studied ligand can be very active in forming complexes with different metal ions. In addition, the sialorphin derivative can also be tested as a bioactive material, which warrants its further in vitro and in vivo studies.

The present work describes the complexation properties of two synthetic nucleosides (used as ligands), i.e. β-D-ribofuranoside-4-pyrimidinone (ribo) and β-D-deoxyribofuranoside-4-pyrimidinone (deoxy) with Ag(I) ions in aqueous solution. The stability constants of the studied coordination entities were calculated potentiometrically. The logarithm values of the overall stability constants of the coordination entities were found to be [Ag-deoxy]+ = 3.07, [Ag-(deoxy)2]+ = 6.90, [Ag-ribo]+ = 3.00 and [Ag-(ribo)2]+ = 6.63. Based on the species distribution curves as a function of CL/CM, the percentage of each coordination entity formed in aqueous solution was estimated (12 % [Ag-deoxy]+; 36 % [Ag-(deoxy)2]+; 16 % [Ag-ribo]+; 26 % [Ag-(ribo)2]+). It was found that the ligands form coordination entities with Ag(I) ions with stoichiometric ratios M : L = 1 : 1 and 1 : 2. Such coordination entities may show potential antiviral, antibacterial, and antitumor properties, which warrants further in vitro and in vivo studies. They may also be of great interest for their application in nanobiotechnology.

The cryptoglandular perianal fistula is a common benign anorectal disorder that is managed mainly with surgery and in some cases may be an extremely challenging condition. Perianal fistulas are often characterized by significantly decreased patient quality of life. Lack of fully recognized pathogenesis of this disease makes it difficult to treat it properly. Recently, adipose tissue hormones have been proposed to play a role in the genesis of cryptoglandular anal fistulas. The expression of adipose tissue hormones and epithelial-to-mesenchymal transition (EMT) factors were characterized based on 30 samples from simple fistulas and 30 samples from complex cryptoglandular perianal fistulas harvested during surgery. Tissue levels of leptin, resistin, MMP2, and MMP9 were significantly elevated in patients who underwent operations due to complex cryptoglandular perianal fistulas compared to patients with simple fistulas. Adiponectin and E-cadherin were significantly lowered in samples from complex perianal fistulas in comparison to simple fistulas. A negative correlation between leptin and E-cadherin levels was observed. Resistin and MMP2 levels, as well as adiponectin and E-cadherin levels, were positively correlated. Complex perianal cryptoglandular fistulas have a reduced level of the anti-inflammatory adipokine adiponectin and have an increase in the levels of proinflammatory resistin and leptin. Abnormal secretion of these adipokines may affect the integrity of the EMT in the fistula tract. E-cadherin, MMP2, and MMP9 expression levels were shifted in patients with more advanced and complex perianal fistulas. Our results supporting the idea of using mesenchymal stem cells in the treatment of cryptoglandular perianal fistulas seem reasonable, but further studies are warranted.

The present work describes the complexation of the anti-inflammatory sialorphin derivative Pal-Lys-Lys-Gln-His-Asn-Pro-Arg (palmitic acid-lysine-lysine-glutamine-histidine-asparagine-proline-arginine) with Cu(II) ions in an aqueous solution, at a temperature of 25.0 ± 0.1 °C, over the whole pH range. The complexing properties were characterized by potentiometric and UV-Vis spectrophotometric methods. The potentiometric method was used to calculate the logarithms of the overall stability constants (log β) and the values of the stepwise dissociation constants (pKa) of the studied complexes. The percentage of each species formed in an aqueous solution was estimated from the species distribution curve as a function of pH. The absorbance (A) and molar absorption coefficient (ε) values for the Cu(II)-sialorphin derivative system were determined with UV-Vis spectroscopy. Our studies indicate that the sialorphin derivative forms stable complexes with Cu(II) ions, which may lead to future biological and therapeutic applications.

Crohn’s disease (CD) is a chronic, relapsing disorder belonging to inflammatory bowel diseases (IBD). It is manifested by relapsing transmural inflammation found in any segment of the gastrointestinal tract. Chronic fatigue is a common and underrecognized symptom of CD for which the prevalence is much higher in the population of CD patients compared to the healthy population. It stems from an intricate web of interactions between various risk factors, and its pathophysiology is still not fully understood. The implementation of routine screening and a holistic, multidisciplinary approach involving psychological support may be crucial in the management of CD patients with chronic fatigue. There is currently no single intervention aimed at decreasing fatigue alone, and its treatment is especially difficult in patients with fatigue persisting despite clinical and endoscopic remission. Extensive research is still needed in order to be able to predict, prevent, identify, and ultimately treat fatigue associated with CD. The aim of this review is to summarize the knowledge on the etiology, diagnosis, and treatment of chronic fatigue in CD patients.

Inflammatory bowel diseases (IBD) and their main representatives, Crohn’s disease and ulcerative colitis, are worldwide health-care problems with constantly increasing frequency and still not fully understood pathogenesis. IBD treatment involves drugs such as corticosteroids, derivatives of 5-aminosalicylic acid, thiopurines, and others, with the goal to achieve and maintain remission of the disease. Nowadays, as our knowledge about IBD is continually growing, more specific and effective therapies at the molecular level are wanted. In our study, we tested novel gold complexes and their potential effect on inflammation and IBD in vitro, in silico, and in vivo. A series of new gold(III) complexes (TGS 404, 512, 701, 702, and 703) were designed and screened in the in vitro inflammation studies. In silico modeling was used to study the gold complexes’ structure vs. their activity and stability. Dextran sulphate sodium (DSS)-induced mouse model of colitis was employed to characterize the anti-inflammatory activity in vivo. Lipopolysaccharide (LPS)-stimulated RAW264.7 cell experiments proved the anti-inflammatory potential of all tested complexes. Selected on the bases of in vitro and in silico analyses, TGS 703 significantly alleviated inflammation in the DSS-induced mouse model of colitis, which was confirmed by a statistically significant decrease in the macro- and microscopic score of inflammation. The mechanism of action of TGS 703 was linked to the enzymatic and non-enzymatic antioxidant systems. TGS 703 and other gold(III) complexes present anti-inflammatory potential and may be applied therapeutically in the treatment of IBD.

Inflammatory bowel disease (IBD) patients often have sleep and mood disorders. Brain-derived neurotrophic factor (BDNF) and proBDNF were shown to modulate interactions between the central nervous system and the gastrointestinal tract, possibly contributing to psychological issues. Anti-tumor necrosis factor (TNF) therapy in IBD can alter BDNF expression and further affect the brain–gut axis. Eighty IBD patients and 44 healthy controls (HCs) were enrolled and divided into subsets based on disease activity and condition (ulcerative colitis (UC)/Crohn’s disease (CD)). Questionnaires evaluating sleep parameters and depression as well as venous blood were collected. The IBD group had a lower expression of BDNF mRNA, but higher proBDNF and BDNF protein concentration than HCs. The UC group had a higher BDNF protein concentration than the CD. BDNF protein was positively correlated to sleep efficiency in the IBD group. Depression severity was associated positively with BDNF mRNA and negatively with BDNF protein in the remission group. Anti-TNF therapy enhanced BDNF mRNA expression. The BDNF pathway might be disturbed in IBD, linking it to sleep disorders and depression. Systemic inflammation could be the main cause of this disruption. BDNF mRNA is a more reliable parameter than protein due to numerous post-translational modifications.

BackgroundCrohn’s disease (CD) is a chronic nonspecific inflammatory bowel disease (IBD) with an increasing incidence worldwide. The etiology of CD is still obscure, but microbial dysbiosis has been recognized as an essential factor contributing to CD. However, few studies have revealed the microbiome’s signatures and reciprocal correlations between multiple sites in patients with CD over different disease stages. This study investigated the specific microbial architectures of the oral cavity, sputum, and ileum in patients with CD in the active and remission stages.MethodsMicrobial samples from the oral cavity, sputum, and ileum were collected from patients with CD in the active and remission stages and healthy controls. The microbial composition was assessed by 16S ribosomal RNA (rRNA) gene sequencing. In addition, bioinformatics methods were used to demonstrate the microbial signatures, functional changes, and correlations between microbiota and clinical data in CD.ResultsCompared with healthy controls, a distinct microbiota dysbiosis in the oral cavity, sputum, and ileum of patients with CD was identified, characterized by alterations in microbiota biodiversity and composition. The oral cavity and sputum microbiota showed significantly lower microbial diversity in patients with CD than in healthy controls. In terms of microbiota composition, the microbiota changes in the oral cavity of patients with CD were similar to those in the sputum, while they were different from those in the ileum. In the oral cavity and sputum of patients with CD, a lower relative abundance of Firmicutes and Actinobacteria was observed compared to healthy controls, which was most prominent in the active stage. In contrast, an increased relative abundance of Fusobacteria, Porphyromonas, and Haemophilus was observed in patients with CD. The predicted metabolic pathways involved in the oral cavity, sputum, and ileum were similar, predominantly involving metabolism, environmental information processing, and genetic information processing.ConclusionThe results revealed the alterations of microbiota architecture in the oral cavity, sputum, and ileum of patients with CD, which varied across disease stages. Studying microbiota dysbiosis may bring new insights into the etiology of CD and lead to novel treatments.

Adhesion G protein-coupled receptor F5 (ADGRF5) is involved inthe neoplastic transformation of some cancer types. However, the significance of ADGRF5 expression signature and the impact of signaling pathways mediated by ADGRF5 during neoplastic transformation of the colon and colorectal cancer (CRC) progression has been poorly examined. Using Gene Expression Omnibus and The Cancer Genome Atlas datasets, we showed that ADGRF5 is overexpressed in the colons of patients with CRC. In line, combined analysis of ADGRF5 expression with clinical characterization revealed an increased expression of ADGRF5 in patients with more advanced stages of CRC compared to patients with early stages of CRC. The Spearman correlation analysis documented numerous genes positively and negatively correlated with the expression pattern of ADGRF5 in the colon of patients with CRC. In the colon of CRC patients, the expression signature of ADGRF5 was associated with genes participating in phosphatidylinositol 3-kinase/Akt, focal adhesion, cell adhesion molecules, and ribosome signaling pathways. Of note, ADGRF5 expression correlated with the levels of tumor-infiltrating immune cells in the colon of CRC patients. Moreover, we found that CRC patients with high expression of ADGRF5 had a significantly lower probability of overall survival and disease-free survival. In conclusion, our results support the prognostic value of ADGRF5 and its potent therapeutic implication in CRC.

Pharmacotherapy for inflammatory bowel disease (IBD) is difficult, and some patients do not respond to currently available treatments. Therefore, the discovery of novel anti-IBD agents is imperative. Our aim was the synthesis of lipidated analogs of sialorphin and the in vitro characterization of their effect on the degradation of Met-enkephalin by neutral endopeptidase (NEP). We also investigated in vivo whether the most active inhibitor (peptide VIII) selected in the in vitro studies could be a potential candidate for the treatment of colitis. Peptides were synthesized by the solid-phase method. Molecular modeling technique was used to explain the effect of fatty acid chain length in sialorphin analogs on the ligand–enzyme interactions. The anti-inflammatory effect was evaluated in the dextran sulphate sodium (DSS)-induced model of colitis in mice. Peptide VIII containing stearic acid turned out to be in vitro the strongest inhibitor of NEP. We have also shown that the length of the chain of stearic acid fits the size of the grove of NEP. Peptides VII and VIII exhibited in vivo similar anti-inflammatory activity. Our results suggest that lipidation of sialorphin molecule is a promising direction in the search for NEP inhibitors that protect enkephalins.

In the present study, the complexing properties of ceftazidime with Fe(III) ions in aqueous solutions were characterized by UV-vis spectrophotometric and potentiometric methods. Using the UV-vis spectrophotometric method, the absorbance values for Fe(III) ions, a third-generation cephalosporin antibiotic (ceftazidime), and the Fe(III)-ceftazidime system were determined. Based on pH-metric studies, the value of the stability constant for the Fe(III)-ceftazidime complex was calculated.

The present work describes the complexation properties of two oxime-containing Schiff bases (used as ligands), viz. 2-hydroxyimino-N′-[1-(2-pyridyl)ethylidene]propanohydrazone (Hpop) and 2-hydroxyimino-N′-[(pyridine-2-yl)methylidene]propanohydrazone (Hpoa), with Co(II) ions in DMSO/water solution. Volumetric (oxygenation) studies were carried out to determine the uptake of molecular oxygen O2 in the formation of the complexes Co(II)-Hpop and Co(II)-Hpoa. The acquired data can be useful in the development of oxygen bioinorganic complexes of metal ions with Schiff base ligands in solution. Their properties allow them to be used as synthetic oxygen transporters. Moreover, the binding of dioxygen could play an important role in the research of catalytic activity by such systems.

Cryptoglandular perianal fistula is a common benign anorectal disorder that is managed mainly with surgery. A fistula is typically defined as a pathological communication between two epithelialized surfaces. More specifically, perianal fistula manifests as an abnormal tract between the anorectal canal and the perianal skin. Perianal fistulas are often characterized by significantly decreased patient quality of life. The cryptoglandular theory of perianal fistulas suggests their development from the proctodeal glands, which originate from the intersphincteric plane and perforate the internal sphincter with their ducts. Involvement of proctodeal glands in the inflammatory process could play a primary role in the formation of cryptoglandular perianal fistula. The objective of this narrative review was to investigate the current knowledge of the pathogenesis of cryptoglandular perianal fistula with the specific aims of characterizing the potential role of proinflammatory factors responsible for the development of chronic inflammation. Further studies are crucial to improve the therapeutic management of cryptoglandular perianal fistulas.

Leaky gut syndrome is a medical condition characterized by intestinal hyperpermeability. Since the intestinal barrier is one of the essential components maintaining homeostasis along the gastrointestinal tract, loss of its integrity due to changes in bacterial composition, decreased expression levels of tight junction proteins, and increased concentration of pro-inflammatory cytokines may lead to intestinal hyperpermeability followed by the development of gastrointestinal and non-gastrointestinal diseases. Translocation of microorganisms and their toxic metabolites beyond the gastrointestinal tract is one of the fallouts of the leaky gut syndrome. The presence of intestinal bacteria in sterile tissues and distant organs may cause damage due to chronic inflammation and progression of disorders, including inflammatory bowel diseases, liver cirrhosis, and acute pancreatitis. Currently, there are no medical guidelines for the treatment or prevention of bacterial translocation in patients with the leaky gut syndrome; however, several studies suggest that dietary intervention can improve barrier function and restrict bacteria invasion. This review contains current literature data concerning the influence of diet, dietary supplements, probiotics, and drugs on intestinal permeability and bacterial translocation.

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. Moreover, the effect of opioid receptor (MOP, DOP, KOP) agonists on the mouse GI tract functions and the EOS components expression in mouse tissues and colonic biopsies from patients with functional constipation were determined. In the oldest mice, the GI peristalsis was significantly impaired as compared to the younger groups. The tissue response to MOP and DOP, but not KOP, agonists weakened with age in vitro; for DOP, it was confirmed in vivo. In the mouse upper GI tract, Oprm1, Oprd1, Oprk1 expression decreased with age; in the colon, Oprm1 expression increased. There were no differences in the expression of these genes in the colonic biopsies from patients >50 years old as compared to the younger group. In conclusion, the age-related impairment of the GI peristalsis may result from reduced MOP and DOP response to the activation with opioid agonists or the alterations in the EOS expression.

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). The aim of the study is to investigate the impact of AMCase inhibitor (OAT-177) on the dextran sulfate sodium (DSS)-induced models of colitis. In the short-term therapeutic protocol, OAT-177 given intragastrically in a 30 mg/kg dose, twice daily, produced a significant (p < 0.001) anti-inflammatory effect, as shown by the macroscopic score. Additionally, OAT-177 significantly decreased TNF-α mRNA levels and MPO activity compared to DSS-only treated mice. Intraperitoneal administration of OAT-177 at a dose of 50 mg/kg caused statistically relevant reduction of the colon length. In the long-term therapeutic protocol, OAT-177 given intragastrically in a dose of 30 mg/kg, twice daily, significantly improved colon length and body weight compared to DSS-induced colitis. This is the first study proving that AMCase inhibitors may have therapeutic potential in the treatment of IBD.

Cancer is one of the leading causes of morbidity and mortality worldwide. Colorectal cancer (CRC) is the third most frequently diagnosed cancer in men and the second in women. Standard patterns of antitumor therapy, including cisplatin, are ineffective due to their lack of specificity for tumor cells, development of drug resistance, and severe side effects. For this reason, new methods and strategies for CRC treatment are urgently needed. Current research includes novel platinum (Pt)- and other metal-based drugs such as gold (Au), silver (Ag), iridium (Ir), or ruthenium (Ru). Au(III) compounds are promising drug candidates for CRC treatment due to their structural similarity to Pt(II). Their advantage is their relatively good solubility in water, but their disadvantage is an unsatisfactory stability under physiological conditions. Due to these limitations, work is still underway to improve the formula of Au(III) complexes by combining with various types of ligands capable of stabilizing the Au(III) cation and preventing its reduction under physiological conditions. This review summarizes the achievements in the field of stable Au(III) complexes with potential cytotoxic activity restricted to cancer cells. Moreover, it has been shown that not nucleic acids but various protein structures such as thioredoxin reductase (TrxR) mediate the antitumor effects of Au derivatives. The state of the art of the in vivo studies so far conducted is also described.

Abstract Background Ayurvedic medicine is based on natural healing methods that use herbal medicine to cleanse the body of toxins and to attain physical and mental regeneration. Triphala (TLP) is one of the most important ayurvedic supplements and is believed to have a beneficial effect on the entire gastrointestinal (GI) tract. Purpose We aim to summarize available literature focused on the components of TLP (Terminalia chebula, Terminalia bellerica and Phyllanthus emblica) and discusse their effectiveness and therapeutic value for improving lower GI symptoms in functional GI disorders, particularly irritable bowel syndrome (IBS). Methods This study is based on pertinent papers that were retrieved by a selective search using relevant keywords in PubMed and ScienceDirect databases. Results The components of TLP are believed to cause restoration of the epithelium lining of the digestive tract, and by exhibiting mild laxative properties facilitate passage of stool in the colon. TLP is rich in polyphenols, vitamin C and flavonoids, which provide antioxidant and anti-inflammatory effects. It also contains various types of acids, such as gallic, chebulagic and chebulinic, which additionally possess cytoprotective and antifungal properties. Conclusion Triphala holds potential in improving lower GI symptoms and may be a valuable and effective addition to standard treatment of IBS. Supplementation of TLP herbal formulations alone or along with other probiotics can be recommended in ongoing clinical studies.

Opioid peptides and opiate drugs such as morphine, mediate their analgesic effects, but also undesired side effects, mostly through activation of the mu opioid receptor. However, delta- and kappa-opioid receptors can also contribute to the analgesic effects of opioids. Recent findings showed that simultaneous activation of multiple opioid receptors may result in additional analgesia with fewer side effects. Here, we evaluated the pharmacological profile of our formerly developed mixed mu/kappa-opioid receptor ligands, Dmt-c[D-Lys-Phe-Phe-Asp]NH2 (C-36) and Dmt-c[D-Lys-Phe-p-CF3-Phe-Asp]NH2 (F-81). The ability of these peptides to cross the blood–brain barrier was tested in the parallel artificial membrane permeability (PAMPA) assay. On the basis of the hot-plate test in mice after central and peripheral administration, analog F-81 was selected for the anti-nociceptive and anti-inflammatory activity assessment after peripheral administration.

Background: Recent studies suggest that lipids, including free fatty acids (FFAs), are necessary for proper μ opioid receptor (MOR) binding and that activation of opioid receptors (ORs) improves intestinal inflammation. The objective of the study was to investigate a possible interaction between the ORs and FFA receptors (FFARs) ligands in the colitis. Methods: The potential synergistic effect of ORs and FFARs ligands was evaluated using mouse model of acute colitis induced by dextran sulfate sodium (DSS, 4%). Compounds were injected intraperitoneally (i.p.) once or twice daily at the doses of 0.01 or 0.02 mg/kg body weight (BW) (DAMGO—an MOR agonist), 0.3 mg/kg BW (DPDPE—a δ OR (DOR) agonist) and 1 mg/kg BW (naloxone—a non-selective OR antagonist, GLPG 0974—a FFAR2 antagonist, GSK 137647—a FFAR4 agonist and AH 7614—a FFAR4 antagonist) for 4 days. Results: Myeloperoxidase (MPO) activity was significantly decreased after DAMGO (0.02 mg/kg BW) and GSK 137647 (1 mg/kg BW) administration and co-administration as compared to DSS group. Conclusions: Treatment with ligands of ORs and FFARs may affect the immune cells in the inflammation; however, no significant influence on the severity of colitis and no synergistic effect were observed.

Perianal fistula in patients with Crohn’s disease is an extremely challenging condition. The disease tends to reoccur, and with current treatment options, a large number of patients are left with active ailment and experience major morbidity. In recent years, hopeful results regarding local use of mesenchymal stem cells (MSCs) in perianal Crohn’s disease have been published. Although to this day there are no clear guidelines determining optimal dosage, injections frequency and culture conditions, their efficiency has proven to be much higher than conventionally used methods. According to studies, they can effectively induce as well as maintain fistula closure. This approach also avoids common side effects related to conventional surgical treatment.

Acute pancreatitis (AP) is an inflammatory disease that causes severe tissue damage. Ghee butter from bovine colostrum (GBBC) is a clarified butter produced by heating milk fat to 40 °C and separating the precipitating protein. As colostrum mainly contains fatty acids (FAs), immunoglobulins, maternal immune cells, and cytokines, we hypothesized that it may exert anti-inflammatory effects. We investigated the effects of GBBC on experimental AP in mice. Two intraperitoneal (ip) injections of L-arginine (8%) were given 1 h apart to generate the AP murine model. After 12 h from the first L-arginine injection, mice were divided into the following experimental groups: AP mice treated with GBBC (oral gavage (po) every 12 h) and non-treated AP mice (po vehicle every 12 h). Control animals received vehicle only. At 72 h, mice were euthanized. Histopathological examination along with myeloperoxidase (MPO) and amylase/lipase activity assays were performed. In a separate set of experiments, FFAR1 and FFAR4 antagonists were used to verify the involvement of respective receptors. Administration of GBBC decreased MPO activity in the pancreas and lungs along with the microscopical severity of AP in mice. Moreover, treatment with GBBC normalized pancreatic enzyme activity. FFAR1 and FFAR4 antagonists tended to reverse the anti-inflammatory effect of GBBC in mouse AP. Our results suggest that GBBC displays anti-inflammatory effects in the mouse model of AP, with the putative involvement of FFARs. This is the first study to show the anti-inflammatory potential of a nutritional supplement derived from GBBC.

Oxidative stress (OS) has been proposed as a significant causative and propagating factor in inflammatory bowel diseases (IBDs). Modulation of OS is possible through antioxidants and inhibition of oxidizing enzymes. Thirty-one IBD patients and thirty-two controls were included in the study. The aim was to examine the levels of OS in colonic tissue of IBD requiring surgical intervention and control group, and their association with pain intensity. Total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase (CAT) activity, glutathione (GSH) and oxidized glutathione (GSSG) levels, and glutathione peroxidase (GPX) activity as markers of antioxidant defense were determined. Cyclooxygenases activities (Total COX, COX-1 and COX-2) were measured as prooxidant enzymes. Thiobarbituric acid reactive substances (TBARS) concentrations were measured to evaluate lipid peroxidation. Disease activity was assessed, and each subject filled out VAS and Laitinen’s pain assessment scales. Correlation between the OS, pain intensity, disease activity parameters, C-reactive protein (CRP), number of stools passed daily, disease duration, and dietary habits was investigated. No TAC differences were found between the groups. A significant decrease of SOD activity and GSH and GSSG levels was seen in IBD patients vs. controls, while GPX activity was diminished significantly only in CD patients. CAT and COX-1 activity was increased, and COX-2 significantly decreased in IBD. TBARS were significantly higher in CD patients compared to control group. No correlation was found between pain scores, inflammatory status, disease activity, disease duration, or dietary habits and OS markers. In our study, OS did not influence pain sensation reported by IBD patients.

Diet is considered an important trigger in inflammatory bowel diseases (IBD), as feeding habits can affect intestinal permeability and clearance of bacterial antigens, consequently influencing the immune system. Free fatty acid receptors (FFARs), expressed on the intestinal epithelial cells, belong to the family of luminal-facing receptors that are responsive to nutrients. The objective of this study was to characterize the anti-inflammatory activity and the effect on intestinal barrier function of synthetic FFAR agonists in mouse models of colitis. Therapeutic activity of GW9508 (FFAR1 agonist), 4-CMTB (FFAR2 agonist), AR420626 (FFAR3 agonist), and GSK137647 (FFAR4 agonist) was investigated in two models of semi-chronic colitis: induced by trinitrobenzenesulfonic acid (TNBS), mimicking Crohn’s disease, as well as induced by dextran sulfate sodium (DSS), which recapitulates ulcerative colitis in humans. Moreover, we assessed the influence of FFARs agonists on epithelial ion transport and measured the ion flow stimulated by forskolin and veratridine. Administration of FFAR4 agonist GSK137647 attenuated both TNBS-induced and DSS-induced colitis in mice, as indicated by macroscopic parameters and myeloperoxidase activity. The action of FFAR4 agonist GSK137647 was significantly blocked by pretreatment with selective FFAR4 antagonist AH7614. Moreover, FFAR1 and FFAR4 agonists reversed the increase in the colon permeability caused by inflammation. FFAR4 restored the tight junction genes expression in mouse colon. This is the first evaluation of the anti-inflammatory activity of selective FFAR agonists, showing that pharmacological intervention targeting FFAR4, which is a sensor of medium and long chain fatty acids, attenuates intestinal inflammation.

Chitinases belong to the evolutionarily conserved glycosyl hydrolase family 18 (GH18). They catalyze degradation of chitin to N-acetylglucosamine by hydrolysis of the β-(1-4)-glycosidic bonds. Although mammals do not synthesize chitin, they possess two enzymatically active chitinases, i.e., chitotriosidase (CHIT1) and acidic mammalian chitinase (AMCase), as well as several chitinase-like proteins (YKL-40, YKL-39, oviductin, and stabilin-interacting protein). The latter lack enzymatic activity but still display oligosaccharides-binding ability. The physiologic functions of chitinases are still unclear, but they have been shown to be involved in the pathogenesis of various human fibrotic and inflammatory disorders, particularly those of the lung (idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, sarcoidosis, and asthma) and the gastrointestinal tract (inflammatory bowel diseases (IBDs) and colon cancer). In this review, we summarize the current knowledge about chitinases, particularly in IBDs, and demonstrate that chitinases can serve as prognostic biomarkers of disease progression. Moreover, we suggest that the inhibition of chitinase activity may be considered as a novel therapeutic strategy for the treatment of IBDs.

Introduction: Adiponectin is a hormone secreted by adipocytes, which exhibits insulin-sensitizing and anti-inflammatory properties and acts through adiponectin receptors: AdipoR1 and AdipoR2. The aim of the study was to evaluate whether activation of adiponectin receptors AdipoR1 and AdipoR2 with an orally active agonist AdipoRon has gastroprotective effect and to investigate the possible underlying mechanism. Methods: We used two well-established mouse models of gastric ulcer (GU) induced by oral administration of EtOH (80% solution in water) or diclofenac (30 mg/kg, p.o.). Gastroprotective effect of AdipoRon (dose 5 and 50 mg /kg p.o) was compared to omeprazole (20 mg/kg p.o.) or 5% DMSO solution (control). Clinical parameters of gastroprotection were assessed using macroscopic (gastric lesion area) and microscopic (evaluation of the gastric mucosa damage) scoring. To establish the molecular mechanism, we measured: myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities; glutathione (GSH) level; and IL-1β, adenosine monophosphate-activated protein kinase (AMPK), and phosphorylated AMPK expression in gastric tissue. Results: AdipoRon produced a gastroprotective effect in both GU mouse models as evidenced by significantly lower macroscopic and microscopic damage scores. AdipoRon exhibited anti-inflammatory effect by reduction in MPO activity and IL-1β expression in the gastric tissue. Moreover, AdipoRon induced antioxidative action, as demonstrated with higher GSH levels, and increased SOD and GPX activity. Conclusions: Activation of AdipoR1 and AdipoR2 using AdipoRon reduced gastric lesions and enhanced cell response to oxidative stress. Our data suggest that AdipoR1 and AdipoR2 activation may be an attractive therapeutic strategy to inhibit development of gastric ulcers.

Dietary modifications, including those affecting dietary fat and its fatty acid (FA) composition, may be involved in the development of brain–gut axis disorders, with different manifestations in males and females. Our aim was to evaluate the impact of three purified diets with different FA composition on the brain–gut axis in rats of both sexes. Male and female Wistar rats fed a cereal-based standard diet from weaning were used. At young adult age (2–3 months old), animals were divided into three groups and treated each with a different refined diet for 6 weeks: a control group fed on AIN-93G diet containing 7% soy oil (SOY), and two groups fed on AIN-93G modified diets with 3.5% soy oil replaced by 3.5% coconut oil (COCO) or 3.5% evening primrose oil (EP). Different brain–gut axis parameters were evaluated during 4–6 weeks of dietary intervention. Compared with SOY diet (14% saturated FAs, and 58% polyunsaturated FAs), COCO diet (52.2% saturated FAs and 30% polyunsaturated FAs) produced no changes in brain functions and minor gastrointestinal modifications, whereas EP diet (11.1% saturated FAs and 70.56% polyunsaturated FAs) tended to decrease self-care behavior and colonic propulsion in males, and significantly increased exploratory behavior, accelerated gastrointestinal transit, and decreased cecum and fecal pellet density in females. Changes in FA composition, particularly an increase in ω-6 polyunsaturated FAs, seem to facilitate the development of brain–gut axis alterations in a sex-dependent manner, with a relatively higher risk in females.

The present study examines the chemical composition of an evening primrose flavanol preparation (EPFP) and its chemopreventive activity in colon cancer SW-480 cells. EPFP was found to inhibit SW-480 cell viability by 67% vs. controls at 150 µM catechin equivalents (CE) following 72 h incubation (IC50 = 65 µM CE). EPFP decreased both NF-κB protein expression (33% vs. control at 100 µM CE) and phosphorylation at serine 529 of the p65 subunit (49% vs. control at 100 µM CE) in SW-480 cells. Moreover, 100 µM CE EPFP suppressed COX-2 mRNA expression to 23% of control values and protein expression to 78%. In addition, EPFP reduced MMP-9 protein expression to 24% vs. controls at 100 µM CE. These results provide the first evidence that EPFP reduces NF-κB, COX-2, and MMP-9 expression, which may suggest it has cytotoxic, anti-inflammatory, and anti-metastatic activities towards colon cancer cells.

Inflammatory bowel diseases (IBD) are at the top of the worldwide rankings for gastrointestinal diseases as regards occurrence, yet efficient and side-effect-free treatments are currently unavailable. In the current study, we proposed a new concept for anti-inflammatory treatment based on gold (III) complexes. A new gold (III) complex TGS 121 was designed and screened in the in vitro studies using a mouse macrophage cell line, RAW264.7, and in vivo, in the dextran sulphate sodium (DSS)-induced mouse model of colitis. Physicochemical studies showed that TGS 121 was highly water-soluble; it was stable in water, blood, and lymph, and impervious to sunlight. In lipopolysaccharide (LPS)-stimulated RAW264.7 cells, the complex showed a potent anti-inflammatory profile, as evidenced in neutral red uptake and Griess tests. In the DSS-induced mouse model of colitis, the complex administered in two doses (1.68 μg/kg, intragastrically, and 16.8 μg/kg, intragastrically, once daily) produced a significant (* p < 0.05) anti-inflammatory effect, as shown by macroscopic score. The mechanism of action of TGS 121 was related to the enzymatic and non-enzymatic antioxidant system; moreover, TGS 121 induced changes in the tight junction complexes expression in the intestinal wall. This is the first study proving that gold (III) complexes may have therapeutic potential in the treatment of IBD.

Due to its immunomodulatory effect, vitamin D has been associated with clinical parameters and outcomes in inflammatory bowel diseases (IBDs) which are chronic conditions of the gastrointestinal tract. Upon synthesis or digestion, vitamin D is metabolized in the liver to form 25(OH)D3, the major circulating metabolite. Further renal hydroxylation generates 1,25(OH)2D3, the most potent metabolite. Our aim was to examine the association between vitamin D levels, and its supplementation and pain intensity in 39 IBD patients and 33 healthy individuals. 25(OH)D3 and 1,25(OH)2D3 serum levels were measured. Each subject filled out visual analog scale (VAS) and Laitinen’s pain assessment scales. Laboratory results were obtained, and disease activity was assessed. Linear regression was employed to investigate the correlation between 25(OH)D3, 1,25(OH)2D3 and pain intensity, clinical activity parameters, C-reactive protein, disease duration, and dietary habits. In IBD patients, 25(OH)D3 was increased, whereas 1,25(OH)2D3 was not. Vitamin D3 supplementation did not influence their levels. No correlation was found between pain scores, disease activity, inflammatory status, disease duration or dietary habits and both forms of vitamin D. Elevated 25(OH)D3 and normal 1,25(OH)D3 were found in IBD patients as compared to the controls. We discovered no effect from supplementation and no association between pain severity and vitamin D.

Background: the pharmacological treatment and/or maintenance of remission in inflammatory bowel diseases (IBDs) is currently one of the biggest challenges in the field of gastroenterology. Method: our aim was the synthesis of homo- and heterodimers of natural enkephalinase inhibitors (opiorphin; sialorphin; spinorphin) and the in vitro characterization of their effect on the degradation of enkephalin by neutral endopeptidase (NEP) and stability in human plasma. We investigated the in vivo heterodimer of Cys containing analogs of sialorphin and spinorphin (peptide X) in a mouse model of colitis. The extent of inflammation was evaluated based on the microscopic score; macroscopic score; ulcer score, colonic wall thickness, colon length and quantification of myeloperoxidase activity. Results: we showed that the homo- and heterodimerization of analogs of sialorphin, spinorphin and opiorphin containing Cys residue at the N-terminal position resulted in dimeric forms which in vitro exhibited higher inhibitory activity against NEP than their parent and monomeric forms. We showed that peptide X was more stable in human plasma than sialorphin and spinorphin. Peptide X exerts potent anti-inflammatory effect in the mouse model of colitis. Conclusion: we suggest that peptide X has the potential to become a valuable template for anti-inflammatory therapeutics for the treatment of gastrointestinal (GI) tract inflammation.

In many countries around the world (including the United States, Canada, and Spain), research is being conducted into the impact of air pollution on the formation of various types of cancer. For a long time it was thought that the inhalation of pollutants could lead to lung diseases. Now the effects of air pollutants on tumors in the airways, kidneys, bladder, breast, and colon have been investigated and are better understood. It is now known that particulates in air pollution can cross the blood–brain barrier and also reach the placenta. The aim of this study was to find a possible relationship between the emission of pollutants into the atmosphere and the formation of specific types of tumors in the Polish population. Two databases available on the Internet were used in the analysis: the bank of measurement data on air quality in Poland (the repository of Environmental Protection Inspection) and cancer statistics. The pollution measurement data for the years 2000–2016 were taken from the Chief Inspectorate for Environmental Protection website, a database with results from 264 stations located in Poland for 13 types of gases and atmospheric pollutants. Statistical data on cancer C00–D09 (according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10)) in the Polish population in the years 1999–2015 were retrieved from onkologia.org.pl. A novel code was constructed, allowing the downloading of statistics from the databases, examination of their correlation, and selection of the best model of regression through machine learning. The results of the analyses indicate a high correlation of air pollution with the incidence of selected types of cancer. Particularly noteworthy is the observed effect of NOx on the incidence of small and large intestine cancers in the Masovia and West Pomerania provinces. The other gases and pollutants with the most significant impact on the incidence of gastrointestinal cancer have also been identified. Based on statistical analysis, we found a correlation between air pollution and tumor incidence in individual provinces, as well as an influence of the emission of nitrogen oxides on the cancer incidence rate.

Ulcerative colitis belongs to inflammatory bowel diseases, which is a group of chronic disorders of the gastrointestinal tract. It is a debilitating condition with a wide range of symptoms including rectal bleeding, diarrhea, and visceral pain. Current dietary habits often lead to imbalance in n-6/n-3 polyunsaturated fatty acids (PUFA) in favor of n-6 PUFA. Recent data showed the potential anti-inflammatory advantage of n-3 PUFA. Walnut oil (WO) is rich in those fatty acids and mainly consists of linoleic and linolenic acids that may act via free fatty acids receptors (FFARs). We assessed the anti-inflammatory effect of WO in the mouse model of dextran sulfate sodium (DSS)-induced colitis. Moreover, we examined changes in the expression of tight junction proteins (TJ), pro-inflammatory cytokines, and FFAR proteins in the inflamed mouse colon. WO improves the damage score in inflamed tissue, significantly restoring ion transport and colonic wall permeability. Inflammation caused changes in TJ, FFAR, and pro-inflammatory gene proteins expression, which WO was able to partially reverse. WO has anti-inflammatory properties; however, its exact mechanism of action remains unclear. This stems from the pleiotropic effects of n-3 PUFA ligands associated with receptor distribution and targeted signaling pathways.

Red cabbage is an important source of vitamins, micro- and macroelements and polyphenols. The aim of our study was to evaluate the anti-inflammatory effect of red cabbage extract (RCE) in mouse models of inflammatory bowel disease (IBD). The effect of RCE on experimental colitis was determined using clinical, macro- and microscopic parameters of inflammation. To study the mechanism of RCE action, the expression of pro-inflammatory cytokines and parameters of oxidative stress were assessed. RCE produced a potent anti-inflammatory action in the mouse model of Crohn's disease, as shown by decreased macroscopic damage score in acute (2.70 ± 0.24 vs. 5.78 ± 0.58 for control group) and chronic (1.81 ± 0.38 vs. 2.94 ± 0.29) colitis model. In the animal model of ulcerative colitis, total macroscopic score was decreased after prophylactic and therapeutic administration (11.9 ± 0.5 and 11.2 ± 0.9 vs. 14.2 ± 0.4 in control group, respectively). Red cabbage extract may be applied as a potential dietary supplement in IBD therapy.

Polyunsaturated fatty acids (PUFAs) are bioactive lipids which modulate inflammation and immunity. They gained recognition in nutritional therapy and are recommended dietary supplements. There is a growing body of evidence suggesting the usefulness of PUFAs in active therapy of various gastrointestinal (GI) diseases.In this review we briefly cover the systematics of PUFAs and their metabolites, and elaborate on their possible use in inflammatory bowel disease (IBD), functional gastrointestinal disorders (FGIDs) with focus on irritable bowel syndrome (IBS), and colorectal cancer (CRC). Each section describes the latest findings from in vitro and in vivo studies, with reports of clinical interventions when available.

In recent years, there has been a significant increase in the clinical use of organometallic compounds and metal complexes for therapeutic purposes including treatment of inflammatory bowel diseases (IBD). Their action is based on the inhibition of the inflow of pro-inflammatory cytokines, the elimination of free radicals or the modulation of intestinal microbiota. In addition, these compounds are intended for use in the diagnosis and treatment of colorectal cancer (CRC) which is often a consequence of IBD. The aim of this study is to critically discuss recent findings on the use of organometallic compounds and metal complexes in the treatment of IBD and CRC and suggest future trends in drug design.

The pathogenesis of inflammatory bowel diseases (IBD) seems to be associated with alterations of immunoregulation. Several lines of evidence suggest that estrogens play a role in the modulation of immune responses and may be related to the etiology of IBD. The purpose of this work was to examine the involvement of G protein-coupled estrogen receptor (GPER), estrogen receptor α (ERα), estrogen receptor β (ERβ) and ERα spliced variants ERα36 and ERα46 in Crohn’s disease (CD) and ulcerative colitis (UC). The studied group included 73 patients with IBD and 31 sex and age-related controls. No differences in serum levels of 17β-estradiol nor of CYP1A1 and SULT1E1 enzymes involved in estrogen catabolism were stated. The expression pattern of estrogen receptors in tissue samples was quantified using real-time PCR and Western blotting. Statistically significant up-regulation of GPER and ERα in both CD and UC as well as down-regulation of ERβ in CD patients was found. However, differences in the expression of estrogen receptors in CD and UC have been identified, depending on the sex and age of patients. In men, up-regulation of GPER, ERα and ERα46 expression was shown in CD and UC patients. In women under 50 years of age, GPER protein level increased in UC whereas ERβ expression tended to decrease in CD and UC patients. In turn, in women over 50 the protein level of ERα increased in UC while ERβ expression decreased in CD patients. Dysregulation of estrogen receptors in the intestinal mucosa of patients with CD and UC indicates that estrogen signaling may play a role in the local immune response and maintain epithelial homeostasis in a gender- and age-dependent manner.

Inflammatory bowel diseases, particularly ulcerative colitis (UC) and lymphocytic colitis (LC), affect many people. The role of melatonin in the pathogenesis of UC is precisely determined, whereas in LC it remains unknown. The aim of this study was to compare the expression of the melatonin-synthesizing enzymes tryptophan hydroxylase (TPH1), arylalkylamine-N-acetyltransferase (AANAT), and N-acetylserotonin methyltransferase (ASMT) in the colonic mucosa and urinary excretion of 6-sulfatoxymelatonin in patients with ulcerative and lymphocytic colitis. The study included 30 healthy subjects (group C), 30 patients with severe ulcerative colitis (group UC), and 30 patients with lymphocytic colitis (group LC). The diagnosis was based on endoscopic, histological, and laboratory examinations. Biopsy specimens were collected from right, transverse, and left parts of the colon. The levels of mRNA expression, TPH1, AANAT, and ASMT were estimated in the colonic mucosa with RT-PCR. The urine concentration of aMT6s was determined by the photometric method. The expression of TPH1, AANAT, and ASMT in colonic mucosa in UC and LC patients was significantly higher than in healthy subjects. Significant differences were found in the urinary aMT6s excretion: group C—13.4 ± 4.8 µg/24 h, group UC—7.8 ± 2.6 µg/24 h (p < 0.01), group LC—19.2 ± 6.1 µg/24 h (p < 0.01). Moreover, a negative correlation was found between fecal calprotectin and MT6s—in patients with UC − r = −0.888 and with LC − r = −0.658. These results indicate that patients with UC and those with LC may display high levels of melatonin-synthesizing enzymes in their colonic mucosa, which could possibly be related to increased melatonin synthesis as an adaptive antioxidant activity.

AST-120 (kremezin) exhibits its favourable effects in reducing the levels of renal toxins by selective adsorption of low molecular weight substances from the intestinal lumen. So far, a vast majority of studies were focused on the role of AST-120 in the treatment of chronic kidney diseases and cardiovascular disorders, and positive therapeutic effects of the agent have already been confirmed in clinical conditions. Up to the present, there are only a few studies regarding the role of AST-120 in irritable bowel syndrome (IBS). Compelling data suggest the ability of the compound to adsorb protein-bound uremic toxins and mast cell derived mediators and to modulate the farnesoid X receptor, which is a bile acid sensor indispensable for maintaining homeostasis in the intestine. In this review we focus on the actions of AST-120 on intestinal permeability, reduction of visceral sensitivity and alteration of gut motility. We also discuss whether AST-120 can mitigate common IBS symptoms, such as abdominal pain, bloating and malfunction of the colonic transit and thus improve the quality of life of patients with IBS.

Crohn’s disease (CD) and ulcerative colitis (UC), which belong to the group of inflammatory bowel diseases (IBD), are chronic inflammatory conditions of the gastrointestinal (GI) tract. Over the last eighty years the overview of IBD has evolved, along with disease symptom recognition, hypotheses on etiology and recommendations for clinical treatment. This review focuses on the clinical aspects of IBD throughout the years and discusses the most recent and future concepts in IBD diagnosis.

Berberine and its derivatives display potent analgesic, anti-inflammatory and anticancer activity. Here we aimed at characterizing the mechanism of action of berberine in the gastrointestinal (GI) tract and cortical neurons using animal models and in vitro tests.The effect of berberine was characterized in murine models mimicking diarrhea-predominant irritable bowel syndrome (IBS-D) symptoms. Then the opioid antagonists were used to identify the receptors involved. Furthermore, the effect of berberineon opioid receptors expression was established in the mouse intestine and rat fetal cortical neurons.In mouse models, berberine prolonged GI transit and time to diarrhea in a dose-dependent manner, and significantly reduced visceral pain. In physiological conditions the effects of berberine were mediated by mu- (MOR) and delta- (DOR) opioid receptors; hypermotility, excessive secretion and nociception were reversed by berberine through MOR and DOR-dependent action. We also found that berberine increased the expression of MOR and DOR in the mouse bowel and rat fetal cortical neurons.Berberine significantly improved IBS-D symptoms in animal models, possibly through mu- and delta- opioid receptors. Berberine may become a new drug candidate for the successful treatment of IBS-D in clinical conditions.

In an attempt to further investigate the role of cannabinoid (CB) system in the pathogenesis of inflammatory bowel diseases, we employed two recently developed ligands, AM841 (a covalently acting CB agonist) and CB13 (a peripherally-restricted CB agonist) to establish whether central and peripheral CB sites are involved in the anti-inflammatory action in the intestine.AM841 (0.01, 0.1 and 1 mg/kg, i.p.) significantly decreased inflammation scores in dextran sulfate sodium (DSS)- and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-treated mice when administered before induction of colitis or as a treatment of existing intestinal inflammation. The effect was absent in CB1, CB2 and CB(1/2)-deficient mice. A peripherally-restricted agonist CB13 did not alleviate colitis when given i.p. (0.1 mg/kg), but significantly decreased inflammation score after central administration (0.1 µg/animal).This is the first evidence that central and peripheral CB receptors are responsible for the protective and therapeutic action of cannabinoids in mouse models of colitis. Our observations provide new insight to CB pharmacology and validate the use of novel ligands AM841 and CB13 as potent tools in CB-related research.

AIMS: Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder, associated with alterations of bowel function, abdominal pain and other symptoms related to the GI tract. Recently the endogenous cannabinoid system (ECS) was shown to be involved in the physiological and pathophysiological control of the GI function. The aim of this pilot study was to investigate whether IBS defining symptoms correlate with changes in endocannabinoids or cannabinoid like fatty acid levels in IBS patients. METHODS: AEA, 2-AG, OEA and PEA plasma levels were determined in diarrhoea-predominant (IBS-D) and constipation-predominant (IBS-C) patients and were compared to healthy subjects, following the establishment of correlations between biolipid contents and disease symptoms. FAAH mRNA levels were evaluated in colonic biopsies from IBS-D and IBS-C patients and matched controls. RESULTS: Patients with IBS-D had higher levels of 2AG and lower levels of OEA and PEA. In contrast, patients with IBS-C had higher levels of OEA. Multivariate analysis found that lower PEA levels are associated with cramping abdominal pain. FAAH mRNA levels were lower in patients with IBS-C. CONCLUSION: IBS subtypes and their symptoms show distinct alterations of endocannabinoid and endocannabinoid-like fatty acid levels. These changes may partially result from reduced FAAH expression. The here reported changes support the notion that the ECS is involved in the pathophysiology of IBS and the development of IBS symptoms.

BACKGROUND: We studied whether short-term exposure to air pollution was associated with non-specific abdominal pain in epidemiologic and animal studies. METHODS: Patients visiting the emergency department with non-specific abdominal pain were identified in Edmonton (1992 to 2002, n = 95,173) and Montreal (1997 to 2002, n = 25,852). We calculated the daily concentrations for ozone (O(3)), nitrogen dioxide (NO(2)), sulfur dioxide (SO(2)), carbon monoxide (CO), and particles