Article
Cell Biology
Sidnee L. Hedrick, Dan Luo, Sophia Kaska, Kumar Kulldeep Niloy, Karen Jackson, Rupam Sarma, Jamie Horn, Caroline Baynard, Markos Leggas, Eduardo R. Butelman, Mary Jeanne Kreek, Thomas E. Prisinzano
Summary: The research aims to identify a novel opioid reversal agent with enhanced efficacy towards fentanyl and other synthetic opioids. Through screening and experiments on a series of naltrexone analogues, a promising lead, analogue 29, has been discovered with potent MOR antagonist activity in vitro and in vivo.
JOURNAL OF BIOMEDICAL SCIENCE
(2021)
Article
Multidisciplinary Sciences
Md Tariqul Haque Tuhin, Dengpan Liang, Fang Liu, Hala Aldawod, Toufiq Ul Amin, Joshua S. Ho, Rasha Emara, Arjun D. Patel, Melanie A. Felmlee, Miki S. Park, James A. Uchizono, Mamoun M. Alhamadsheh
Summary: The study develops a drug delivery approach to limit the passage of small molecules across the blood-brain barrier, and also develops new potent analgesics that have a significant impact on the central nervous system.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Mengna Zhang, Biao Xu, Ning Li, Run Zhang, Qinqin Zhang, Xuerui Shi, Kangtai Xu, Jian Xiao, Dan Chen, Jiandong Niu, Yonghang Shi, Quan Fang
Summary: Stable and orally bioavailable analogues of DN-9 achieving peripherally restricted analgesia with reduced side effects have been developed. Among these analogues, analogue 1 showed improved potency for kappa-opioid and NPFF2 receptors and exhibited powerful, long-lasting antinociceptive effects in mouse models of acute, inflammatory, and neuropathic pain without significant side effects at effective analgesic doses.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Boshi Huang, Mengchu Li, Pornprom Klongkumnuankarn, Rolando E. Mendez, James C. Gillespie, David L. Stevens, William L. Dewey, Dana E. Selley, Yan Zhang
Summary: Opioid-induced constipation (OIC) is a common side effect of opioid analgesics. Peripherally acting mu opioid receptor antagonists (PAMORAs) can effectively treat OIC without affecting the analgesic effects. A new compound has shown promising results in improving intestinal motility and may be developed as an oral treatment for constipation.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Jacob K. Meariman, Jane C. Sutphen, Juan Gao, Donald E. Mercante, Daniel R. Kapusta
Summary: In this study, the cardiovascular and renal responses to Difelikefalin were investigated, and the effects of the KOR antagonist norBNI on Difelikefalin and nalfurafine were examined. The results showed that Difelikefalin induced diuresis and decreased MAP through the central KOR pathway, while enhancing renal tubular electrolyte reabsorption through the peripheral KOR pathway.
PHARMACOLOGICAL RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Anna Abrimian, Tamar Kraft, Ying-Xian Pan
Summary: Endogenous opioid peptides, including enkephalins, dynorphins, and beta-endorphin, act through MOR, DOR, and KOR receptors, playing important roles in analgesia and various biological processes. The OPRM1 gene undergoes extensive pre-mRNA splicing, generating multiple splice variants, with the 7TM C-terminal variants playing a key role in the pharmacological functions of endogenous opioid peptides.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Xin Wang, Xiaoli Gou, Xiaojuan Yu, Dongdong Bai, Bowei Tan, Pingfeng Cao, Meilin Qian, Xiaoxiao Zheng, Hairong Wang, Pingming Tang, Chen Zhang, Fei Ye, Jia Ni
Summary: Kappa opioid receptor (KOR) agonists have potential for pain relief and treating pruritus, but their development is hindered by sedation, dysphoria and diuresis. The study on HSK21542 showed it to be a selective and potent KOR agonist with peripheral selectivity, providing a safe and effective alternative for patients suffering from pain and pruritus.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Agata Szymaszkiewicz, Marcin Talar, Jakub Wlodarczyk, Mikolaj Swierczynski, Adrian Bartoszek, Julia Krajewska, Anna Mokrowiecka, Ewa Malecka-Wojciesko, Jakub Fichna, Marta Zielinska
Summary: Nearly 20% of elderly patients suffer from constipation, but the age-related changes in the gastrointestinal (GI) tract remain insufficiently elucidated. This study evaluated the alterations within the endogenous opioid system (EOS) as a potential cause of constipation in the elderly. The results showed that the age-related impairment of GI peristalsis may result from reduced MOP and DOP response to opioid agonists or alterations in EOS expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Physiology
Mohammad Alqudah, Othman Al-Shboul, Ahmed Al-Dwairi, Doa'a G. Al-Udat, Abdelrahim Alqudah
Summary: Progesterone is a crucial hormone with various functions in the body. Apart from maintaining pregnancy and promoting endometrial differentiation, progesterone also plays a role in the nervous system, bone, vascular system, and gastrointestinal tract. Recent literature indicates that progesterone inhibits gut smooth muscle cells, thus contributing to the regulation of normal gastrointestinal motility.
PHYSIOLOGICAL RESEARCH
(2022)
Article
Neurosciences
Danxu Ma, Qian Huang, Xinyan Gao, Neil C. Ford, Ruijuan Guo, Chi Zhang, Shuguang Liu, Shao-Qiu He, Srinivasa N. Raja, Yun Guan
Summary: Drugs targeting the opioid receptor outside the central nervous system have shown promise in treating pain after spinal cord injury. Asimadoline adversely affected behavior in SCI mice, suggesting CNS drug penetration. In contrast, ICI-204448 reduced pain hypersensitivity without side effects, suggesting its potential as a treatment for SCI pain.
Article
Biochemistry & Molecular Biology
Luis Santos-Molina, Alexa Herrerias, Charles N. Zawatsky, Ozge Gunduz-Cinar, Resat Cinar, Malliga R. Iyer, Casey M. Wood, Yuhong Lin, Bin Gao, George Kunos, Grzegorz Godlewski
Summary: The activation of peripheral CB1 receptors plays a dominant role in promoting alcohol intake, while the iNOS inhibitory function of MRI-1867 helps in mitigating the alcohol-induced increase in endotoxemia.
Review
Biochemistry & Molecular Biology
Yasuyuki Tanahashi, Seiichi Komori, Hayato Matsuyama, Takio Kitazawa, Toshihiro Unno
Summary: The article reviews the mechanism of mAChRs in regulating gastrointestinal smooth muscle function and highlights the major signaling events induced by mAChRs. Challenges in studying individual mAChR subtypes and the need for novel strategies such as genetic manipulation are emphasized.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Gastroenterology & Hepatology
Jesse J. DiCello, Simona E. Carbone, Ayame Saito, Vi Pham, Agata Szymaszkiewicz, Arisbel B. Gondin, Sadia Alvi, Kiliana Marique, Priyank Shenoy, Nicholas A. Veldhuis, Jakub Fichna, Meritxell Canals, Arthur Christopoulos, Celine Valant, Daniel P. Poole
Summary: This study investigates the modulation of delta opioid receptor in the enteric nervous system using allosteric modulators, demonstrating the potential of positive allosteric modulation as a pharmacological approach to enhance opioid receptor signaling and suppress colonic motility. The findings suggest that allosteric modulation of opioid receptor signaling could be a therapeutic strategy for conditions such as irritable bowel syndrome.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Review
Medicine, General & Internal
Martina Rekatsina, Antonella Paladini, Asbjorn M. Drewes, Farrah Ayob, Omar Viswanath, Ivan Urits, Oscar Corli, Joseph Pergolizzi, Giustino Varrassi
Summary: Opioids are commonly used for treating chronic and acute pain, but can lead to adverse events such as opioid-induced bowel dysfunction, specifically opioid-induced constipation. Peripherally acting mu-opioid receptor antagonists (PAMORAs) have been developed to counteract these effects. Different PAMORAs have varying efficacy and tolerability profiles, with naloxegol and naldemedine showing promising results in reducing opioid-induced constipation.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2021)
Article
Medicine, Research & Experimental
Mathias E. Cook, Cecilie S. Knoph, Camilla A. Fjelsted, Jens B. Frokjaer, Anders E. Bilgrau, Srdan Novovic, Maiken Thyregod Jorgensen, Michael B. Mortensen, Liv B. J. Nielsen, Amer Hadi, Mark Berner-Hansen, Wiktor Rutkowski, Miroslav Vujasinovic, Matthias Lohr, Asbjorn M. Drewes, Soren S. Olesen
Summary: This study aims to investigate whether naldemedine can alter the natural course of pancreatitis in patients with recurrent acute pancreatitis and improve patient outcomes.
Article
Biochemistry & Molecular Biology
Agata Twardowska, Adam Makaro, Agata Binienda, Jakub Fichna, Maciej Salaga
Summary: Leaky gut syndrome is a medical condition characterized by intestinal hyperpermeability. Changes in bacterial composition, decreased expression levels of tight junction proteins, and increased concentration of pro-inflammatory cytokines can lead to intestinal hyperpermeability and the development of various diseases. Translocation of microorganisms and their toxic metabolites beyond the gastrointestinal tract can cause chronic inflammation and progression of disorders. Dietary intervention has shown potential in improving barrier function and restricting bacterial invasion, but there are no medical guidelines for the treatment or prevention of bacterial translocation in patients with leaky gut syndrome.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Tomasz Mackiewicz, Damian Jacenik, Marcin Talar, Jakub Fichna
Summary: This study suggests that the expression of GPR35 is associated with survival rates in colorectal cancer patients and has prognostic value for male patients.
PHARMACOLOGICAL REPORTS
(2022)
Article
Cell & Tissue Engineering
Jian Wan, Tianqi Wu, Ying Liu, Muqing Yang, Jakub Fichna, Yibing Guo, Lu Yin, Chunqiu Chen
Summary: In this study, a 3D culture model based on decellularized intestinal scaffolds (DIS) was developed, and it was found that MCs tryptase and TGF-beta 1 could promote the differentiation of fibroblasts into fibrotic-phenotype myofibroblasts in the 3D model through Akt and Smad2/3 signaling pathways. This study provides a new platform for intestinal disease modeling and screening of genes and signaling pathways.
TISSUE ENGINEERING AND REGENERATIVE MEDICINE
(2022)
Article
Medicine, Research & Experimental
Tomasz Mackiewicz, Jakub Wlodarczyk, Marta Zielinska, Marcin Wlodarczyk, Adam Durczynski, Piotr Hogendorf, Lukasz Dziki, Jakub Fichna
Summary: This study measured the expression of GPR35 in colorectal cancer (CRC) and pancreatic adenocarcinoma (PDAC) patients using real-time polymerase chain reaction (RT-PCR). The results showed significantly higher GPR35 expression in tumor samples compared to paired healthy samples, and correlations with tumor characteristics were observed. These findings suggest the potential prognostic value of GPR35 testing in CRC and PDAC patients.
ADVANCES IN CLINICAL AND EXPERIMENTAL MEDICINE
(2023)
Review
Medicine, General & Internal
Jakub Wlodarczyk, Jacek Burzynski, Bartlomiej Czerwinski, Mateusz Prusisz, Katarzyna Socala, Ewa Poleszak, Jakub Fichna, Kasper Marynczak, Marcin Wlodarczyk, Lukasz Dziki
Summary: Crohn's disease is a subtype of chronic inflammatory bowel diseases characterized by skip lesions and transmural inflammation. It can affect the entire gastrointestinal tract and persistent pain is one of the main symptoms. This study aims to provide an abbreviated summary of the current knowledge on the origins and treatment of pelvic pain in Crohn's disease.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Marek Pajak, Magdalena Wozniczka, Miroslawa Swiatek, Bartlomiej Czerwinski, Jakub Wlodarczyk, Jakub Fichna
Summary: The complexation properties of two synthetic nucleosides, beta-D-ribofuranoside-4-pyrimidinone (ribo) and beta-D-deoxyribofuranoside-4-pyrimidinone (deoxy), with Ag(I) ions in aqueous solution were investigated. The stability constants of the coordination entities formed were calculated and the percentage of each entity in solution was estimated. The results suggest that these coordination entities have potential antiviral, antibacterial, and antitumor properties, as well as potential applications in nanobiotechnology.
ACTA POLONIAE PHARMACEUTICA
(2023)
Review
Pharmacology & Pharmacy
Karolina Merecz, Mikolaj Hirsa, Olga Biniszewska, Jakub Fichna, Aleksandra Tarasiuk
Summary: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that affects approximately 10% of the global population. Recent studies have shown that antagonism of the serotonin 5-HT3 receptor is an effective treatment for IBS-D. The modulation of serotonin function plays a crucial role in maintaining intestinal homeostasis.
EXPERT OPINION ON PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Jakub Wlodarczyk, Julia Krajewska, Lukasz Szeleszczuk, Patrycja Szalwinska, Agata Gurba, Szymon Lipiec, Przemyslaw Taciak, Remigiusz Szczepaniak, Izabela Mlynarczuk-Bialy, Jakub Fichna
Summary: Inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis, are global health problems with increasing frequency and unclear pathogenesis. Current treatment involves drugs like corticosteroids and derivative compounds, but more specific and effective therapies are desired. In this study, novel gold complexes were tested and found to have anti-inflammatory potential both in vitro and in vivo, particularly TGS 703, which was able to alleviate inflammation in a mouse model of colitis and showed a link to antioxidant systems. These findings suggest that gold(III) complexes may have therapeutic applications in the treatment of IBD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Joanna Drogosz-Stachowicz, Katarzyna Gach-Janczak, Marek Mirowski, Jacek Pietrzak, Tomasz Janecki, Anna Janecka
Summary: The antitumor activity of a synthetic analog, AJ-418, with a 5,8-quinolinedione scaffold was investigated on breast cancer cell lines. AJ-418 showed strong antiproliferative activity against MCF-7 and MDA-MB-231 cells with lower cytotoxicity towards healthy MCF-10A cells. The compound induced morphological changes and apoptosis in cancer cells, while remaining unaffected in non-tumorigenic cells.
Review
Pharmacology & Pharmacy
Jacek Burzynski, Jakub Fichna, Aleksandra Tarasiuk
Summary: Acute pancreatitis (AP) and chronic pancreatitis (CP) are severe diseases that pose a great threat to human health in high-income countries. Oxidative stress plays a significant role in the development of AP and CP, and there is growing interest in the use of antioxidant therapy to manage these conditions. Vitamin A, a well-known antioxidant, has been understudied in relation to its impact on oxidative stress in AP and CP. This review aims to evaluate the molecular targets of vitamin A and its potential role in attenuating oxidative stress in AP and CP. The findings suggest that vitamin A may influence several molecular pathways involved in antioxidative defense and cytoprotection, indicating its potential to alter the disease course of AP and CP.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2023)
Article
Toxicology
Szymon Lipiec, Agata Gurba, Izabela M. Agnieszczak, Andrzej Antoni Szczepankiewicz, Przemyslaw Szymanski, Przemyslaw Taciak, Remigiusz Szczepaniak, Lukasz Szeleszczuk, Hanna Nieznanska, Jakub Wlodarczyk, Jakub Fichna, Lukasz P. Bialy, Izabela Mlynarczuk-Bialy
Summary: Metal-based agents in cancer therapy, like cisplatin and its derivates, have established clinical applications but also can induce serious side effects. Thus, metallotherapeutic alternatives for platinum derivatives are developed and intensively studied. Platinum is replaced by several transition metals including gold. Especially gold (III) complexes can have the same square-planar structure and are isoelectric with platinum (II).
TOXICOLOGY IN VITRO
(2023)
Article
Immunology
Adam Makaro, Mikolaj Swierczynski, Kacper Pokora, Barbara Sarniak, Radzislaw Kordek, Jakub Fichna, Maciej Salaga
Summary: Inflammatory bowel diseases (IBD) is a chronic and relapsing inflammation in the gastrointestinal tract. The incidence and prevalence of IBD are high and increasing, and current therapeutic strategies are suboptimal. This study focused on gliflozins, a group of anti-diabetic drugs, and found that they have anti-inflammatory properties. In vitro experiments showed that two gliflozins, EMPA and DAPA, suppressed nitric oxide production in macrophages, and in vivo experiments demonstrated that EMPA alleviated colitis in mice. Our findings suggest that SGLT-2 inhibitors have anti-inflammatory effects independent of their hypoglycemic effects.
INFLAMMOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Marcin Sochal, Marta Ditmer, Agata Binienda, Agata Gabryelska, Piotr Bialasiewicz, Renata Talar-Wojnarowska, Jakub Fichna, Ewa Malecka-Wojciesko
Summary: Inflammatory bowel disease (IBD) patients often experience sleep and mood disorders which may be related to the disruption of the brain-gut axis. This study found that IBD patients had lower expression of BDNF mRNA but higher concentrations of proBDNF and BDNF protein compared to healthy controls. BDNF protein levels were positively correlated with sleep efficiency in the IBD group and depression severity was associated with BDNF mRNA and protein levels in the remission group.
Article
Medicine, General & Internal
Marcin Sochal, Alicja Witkowska, Agata Binienda, Agata Gabryelska, Piotr Bialasiewicz, Jakub Fichna, Renata Talar-Wojnarowska, Ewa Malecka-Wojciesko
Summary: The study investigates the impact of the serotonergic pathway on the pathogenesis and course of inflammatory bowel diseases (IBDs), and its relationship with sleep and mood disorders. The results show that patients with active IBD have higher levels of 5-HT and SERT protein expression, which are positively correlated with insomnia severity. After treatment, only 5-HT levels are decreased.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Biology
Marcin Wlodarczyk, Adam Makaro, Mateusz Prusisz, Jakub Wlodarczyk, Marta Nowocien, Kasper Marynczak, Jakub Fichna, Lukasz Dziki
Summary: Crohn's disease (CD) is a chronic, relapsing inflammatory bowel disease characterized by transmural inflammation in the gastrointestinal tract. Chronic fatigue is a common and often underestimated symptom in CD patients, with a higher prevalence compared to the general population. Its underlying causes and mechanisms are complex and not fully understood. Routine screening and a comprehensive, multidisciplinary approach, including psychological support, may play a crucial role in managing CD patients with chronic fatigue. Further research is needed to predict, prevent, identify, and treat fatigue associated with CD. This review aims to summarize the current knowledge on the etiology, diagnosis, and treatment of chronic fatigue in CD patients.
