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| 1 | Distribution,function and physiological role of melatonin in the lower gut显示文摘Melatonin is a hormone with endocrine, paracrine andautocrine actions. It is involved in the regulation of multiple functions, including the control of the gastroin-testinal (GI) system under physiological and pathophys-iological conditions. Since the gut contains at least 400times more melatonin than the pineal gland, a reviewof the functional importance of melatonin in the gutseems useful, especially in the context of recent clinicaltrials. Melatonin exerts its physiological effects throughspecific membrane receptors, named melatonin-1 re-ceptor (MT1), MT2 and MT3. These receptors can befound in the gut and their involvement in the regulationof GI motility, inflammation and pain has been reportedin numerous basic and clinical studies. Stable levels ofmelatonin in the lower gut that are unchanged follow-ing a pinealectomy suggest local synthesis and, further more, implicate physiological importance of endogenous melatonin in the GI tract. Presently, only a small number of human studies report possible beneficial and also possible harmful effects of melatonin in case reports and clinical trials. These human studies include patients with lower GI diseases, especially patients with irritable bowel syndrome, inflammatory bowel disease and colorectal cancer. In this review, we summarize the presently available information on melatonin effects in the lower gut and discuss available in vitro and in vivo data. We furthermore aim to evaluate whether melatonin may be useful in future treatment of symptoms or diseases involving the lower gut. | Chun-Qiu Chen Jakub Fichna Mohammad Bashashati Yong-Yu Li Martin Storr | 2011 | World Journal of Gastroenterology2011，17，34： | 13 |
| 2 | Role of environmental pollution in irritable bowel syndrome显示文摘Irritable bowel syndrome(IBS),with the prevalence of 10%-20 % of the population has become an emerging problem worldwide. IBS is a functional gastrointestinal(GI) disorder characterized by abdominal pain or discomfort and altered bowel habits. The etiology of IBS contains genetic,psychological,and immunological factors,and has not been fully elucidated; of note,recent studies also point at environmental pollution and its role in the development of functional GI diseases. In this review we focus on several environmental factors,such as bacterial contamination,air pollution,radiation and even stress as potential triggers of IBS. We discuss associated disturbances in homeostasis,such as changes in intestinal microbiome and related pathophysiological mechanisms. Based on the effect of environmental factors on the GI tract,we also propose novel targets in IBS treatment. | Mateusz Marynowski Aleksandra Likońska Hubert Zatorski Jakub Fichna | 2015 | World Journal of Gastroenterology2015，21，40： | 10 |
| 3 | Inhibition of ileal bile acid transporter:An emerging therapeutic strategy for chronic idiopathic constipation显示文摘Chronic idiopathic constipation is a common disorder of the gastrointestinal tract that encompasses a wide profile of symptoms. Current treatment options for chronic idiopathic constipation are of limited value; therefore, a novel strategy is necessary with an increased effectiveness and safety. Recently, the inhibition of the ileal bile acid transporter has become a promising target for constipation-associated diseases. Enhanced delivery of bile acids into the colon achieves an accelerated colonic transit, increased stool frequency, and relief of constipationrelated symptoms. This article provides insight into the mechanism of action of ileal bile acid transporter inhibitors and discusses their potential clinical use for pharmacotherapy of constipation in chronic idiopathic constipation. | Paula Mosińska Jakub Fichna Martin Storr | 2015 | World Journal of Gastroenterology2015，21，24： | 4 |
| 4 | Antinociceptive effects of novel melatonin receptor agonists in mouse models of abdominal pain显示文摘AIM: To characterize the antinociceptive action of the novel melatonin receptor(MT) agonists, Neu-P11 and Neu-P12 in animal models of visceral pain. METHODS: Visceral pain was induced by intracolonic(ic) application of mustard oil or capsaicin solution or by intraperitoneal(ip) administration of acetic acid. Neu-P11, Neu-P12, or melatonin were given ip or orally and their effects on pain-induced behavioral responses were evaluated. To identify the receptors involved, thenon-selective MT1/MT2 receptor antagonist luzindole, the MT2 receptor antagonist 4-P-PDOT, or the μ-opioid receptor antagonist naloxone were injected ip or intracerebroventricularly(icv) prior to the induction of pain. RESULTS: Orally and ip administered melatonin, Neu-P11, and Neu-P12 reduced pain responses in a dose-dependent manner. Neu-P12 was more effective and displayed longer duration of action compared to melatonin. The antinociceptive effects of Neu-P11 or Neu-P12 were antagonized by ip or icv. administered naloxone. Intracerebroventricularly, but not ip administration of luzindole or 4-P-PDOT blocked the antinociceptive actions of Neu-P11 or Neu-P12. CONCLUSION: Neu-P12 produced the most potent and long-lasting antinociceptive effect. Further development of Neu-P12 for future treatment of abdominal pain seems promising. | Chunqiu Chen Jakub Fichna Moshe Laudon Martin Storr | 2014 | World Journal of Gastroenterology2014，20，5： | 3 |
| 5 | Nociceptin effect on intestinal motility depends on opioidreceptor like-1 receptors and nitric oxide synthase colocalization显示文摘AIM: To study the effect of the opioid-receptor like-1(ORL1) agonist nociceptin on gastrointestinal(GI)myenteric neurotransmission and motility. METHODS: Reverse transcriptase- polymerase chain reaction and immunohistochemistry were used to localize nociceptin and ORL1 in mouse tissues. Intracellular electrophysiological recordings of excitatory and inhibitory junction potentials(EJP, IJP) were made in a chambered organ bath. Intestinal motility was measured in vivo. RESULTS: Nociceptin accelerated whole and upper GI transit, but slowed colonic expulsion in vivo in an ORL1-dependent manner, as shown using [Nphe1]NOC and AS ODN pretreatment. ORL1 and nociceptin immunoreactivity were found on enteric neurons. Nociceptin reduced the EJP and the nitric oxide-sensitive slow IJP in an ORL1-dependent manner, whereas the fast IJP was unchanged. Nociceptin further reduced the spatial spreading of the EJP up to 2 cm. CONCLUSION: Compounds acting at ORL1 are good candidates for the future treatment of disorders associated with increased colonic transit, such as diarrhea or diarrhea-predominant irritable bowel syndrome. | Andrei Sibaev Jakub Fichna Dieter Saur Birol Yuece Jean-Pierre Timmermans Martin Storr | 2015 | World Journal of Gastrointestinal Pharmacology and Therapeutics2015，6，3： | 2 |
| 6 | Correlations between skin lesions induced by anti-tumor necrosis factor-α and selected cytokines in Crohn's disease patients显示文摘AIM:To investigate the correlation between the appearance of skin lesions and concentration of interleukin(IL)-17A,IL-23 and interferon-γ(IFN-γ)in Crohn’s disease(CD)patients during anti-tumor necrosis factor-α(TNF-α)therapy METHODS:A prospective study included 30 adult patients with CD of Caucasian origin(19 men and 11women;mean age±SD 32.0±8.6 years)during biological therapy with anti-TNF-αantibodies from January2012 to March 2013.Eighteen patients were treated with infliximab,seven with adalimumab and five withcertolizumab.Inclusion criteria were exacerbation of the underlying disease,Crohn’s Disease Activity Index over 300 and the ineffectiveness of previously used non-biological therapies.Patients with a history of psoriasis,atopic dermatitis and other autoimmune skin lesions were excluded from the study.The control group consisted of 12 healthy subjects.A diagnostic survey was carried out,blood tests and careful skin examination were performed,and the serum levels of IL-17,IL-23 and IFN-γwere measured using an enzyme-linked immunosorbent assays technique.Dermatoses that have developed in the course of biological therapy in patients who had no pre-existing skin lesions of similar character were qualified as skin lesions induced by antiTNF-αtherapy.RESULTS:Skin manifestations occurred in 18 of CD patients during the anti-TNF-αtherapy(60%),in the average time of 10.16±3.42 mo following the beginning of the 52-wk treatment cycle.Skin lesions observed in CD patients during biological therapy included psoriasiform lesions(44.4%),and eczema forms lesions(22.2%).In CD patients with drug induced skin lesions significantly higher levels of hemoglobin(13.3±1.5 g/dL vs 10.8±1.9 g/dL,P=0.018)and hematocrit(39.9%±4.5%vs 34.3%±5.4%,P=0.01),as well as a significantly lower level of platelets(268±62×103/μL vs 408±239×103/μL,P=0.046)was observed compared with CD patients without skin manifestations.The concentrations of IL-17A and IL-23in CD patients with skin lesions developed under antiTNF-αtherapy were significantly higher compared to those in patients without lesions(IL-17A:39.01±7.03pg/mL vs 25.71±4.90 pg/mL,P=0.00004;IL-23:408.78±94.13 pg/mL vs 312.15±76.24 pg/mL,P=0.00556).CONCLUSION:Skin lesions in CD patients during bio-logical therapy may result from significantly increased concentrations of IL-17A and IL-23,which are strongly associated with TNF-α/Th1 immune pathways. | Marcin Wodarczyk Aleksandra Sobolewska Bartosz Wójcik Karolina Loga Jakub Fichna Maria Wisniewska-Jarosińska | 2014 | World Journal of Gastroenterology2014，20，22： | 2 |
| 7 | Synthesis of target-specific radiolabelld peptides for diagnostic imaging 显示文摘 | Fichna J Janecka A | 2003 | Bioconjug Chem2003，14，1： | 1 |
| 8 | The role of morphine in regulation of cancer cell growth显示文摘 | Gach K Wyr(e)bska A Fichna J | | 0，，03： | 1 |
| 9 | Neutrophil ge- latinase-associated lipocalin and Cathepsin L as early pre- dictors of kidney dysfunction in children with type 1 diabe- tes显示文摘 | Soltysiak J Skowron'ska B Fichna P | 2014 | Endokrynologia Polska2014，65，6： | 1 |
| 10 | Opioid receptors and their ligands显示文摘 | JANECKA A FICHNA J JANECKI T | 2004 | Curr Top Med Chem2004，4，1： | 1 |
| 11 | Polyphenols as mitochondria-targeted anticancer drugs显示文摘 | GORLACH S FICHNA J LEWANDOWSKA U | 2015 | Cancer Letters2015，366，2： | 1 |
| 12 | Functional characterization of opioid receptor ligands by aequorin luminescence-based calcium assay显示文摘 | Fichna J Gach K Piestrzeniewicz M | 2006 | J Pharmacol Exp Ther2006，317，3： | 1 |
| 13 | The role of morphine in regulation of cancer cell growth显示文摘 | Gach K Wyrebska A Fichna J | | 0，，03： | 1 |
| 14 | Experimental colitis in mice is attenuated by changes in the levels of endocannabinoid metabolites induced by selective inhibition of fatty acid amide hydrolase (FAAH)显示文摘 | M. Sa?aga A. Mokrowiecka P.K. Zakrzewski A. Cygankiewicz E. Leishman M. Sobczak H. Zatorski E. Ma?ecka-Panas R. Kordek M. Storr W.M. Krajewska H.B. Bradshaw J. Fichna | 2014 | Journal of Crohn’s and Colitis2014，，： | 1 |
| 15 | The influence of opioids on uroki- nase plasminogen activator on protein and mRNA level in MCF-7 breast cancer cell line 显示文摘 | Gach K Szemraj J Fichna J | 2009 | Chem Biol Drug Des2009，74，4： | 1 |
| 16 | Normal-range albuminuria does not exclude nephropathy in diabetic children 显示文摘 | Zaehwieja J Sohysiak J Fichna P | 2010 | Pediatr Nephrol2010，25，8： | 1 |
| 17 | The influence of opi- oids on urokinase plasminogen activator on protein and mRNA level in MCF-7 breast cancer cell line 显示文摘 | Gaeh K Szemraj J Fichna J | 2009 | Chem Biol Drug Des2009，74，4： | 1 |
| 18 | The endomorphin system and its evolving neurophysiological role 显示文摘 | Fichna J Janecka A Costentin J | 2007 | Phar- macol Rev2007，59，： | 1 |
| 19 | Characterization of the effects of opiorphin and sialorphin and their analogs substituted in position 1 with pyroglutamic acid on motility in the mouse ileum显示文摘 | El?bieta Kamysz Maciej Sa?aga Marta Sobczak Wojciech Kamysz Jakub Fichna | 2013 | J Pept Sci2013，，3： | 1 |
| 20 | Brain Gut Interactions in IBS 显示文摘 | Fichna J Storr MA | 2012 | Front Pharmacol2012，3，： | 1 |
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