Article
Pharmacology & Pharmacy
Long He, Shuting Wen, Zhuotai Zhong, Senhui Weng, Qilong Jiang, Hong Mi, Fengbin Liu
Summary: The combination of 5-ASA and SAHA showed lower toxicity and alleviated inflammation more effectively in the treatment of UC. One possible mechanism of synergy is the synergistic inhibition of the NF-kB signaling pathway.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Hossein Shahdadi Sardou, Fatemeh Sadeghi, Hadi Afrasiabi Garekani, Abbas Akhgari, Amir Hossein Jafarian, Mohammadreza Abbaspour, Ali Nokhodchi
Summary: The aim of this study was to evaluate and optimize the combination of time and pH-dependent polymers as a single coating for the design of the colon-specific drug delivery system of 5-aminosalicylic acid (5-ASA) pellets. The ratio of ES:EL:EC of 33:52:15 w/w at a coating level of 7% was discovered as the optimum coating for the delivery of 5-ASA matrix pellets to the colon.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Riccardo Capecchi, Paola Migliorini, Federico Zanzi, Simona Maltinti, Ilaria Puxeddu, Nicola de Bortoli, Massimo Bellini, Francesco Costa, Santino Marchi, Lorenzo Bertani
Summary: The study demonstrated a correlation between Ig glycosylation and disease activity in UC patients, suggesting a potential role for lectin-selected Ig in predicting therapeutic effectiveness. If confirmed, Ig glycosylation could serve as a biomarker in UC.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Gastroenterology & Hepatology
Ohad Atia, Ramit Magen Rimon, Natan Ledderman, Shira Greenfeld, Revital Kariv, Yiska Loewenberg Weisband, Ron Shaoul, Eran Matz, Shmuel Odes, Idan Goren, Henit Yanai, Iris Dotan, Dan Turner
Summary: A nationwide study in Israel showed that 18% of patients with UC do not receive maintenance treatment, and half of them remain untreated after 3 years. The outcomes of untreated patients were similar to those of treated patients. Further research is needed to explore the role of NMT in UC.
INFLAMMATORY BOWEL DISEASES
(2023)
Review
Biochemistry & Molecular Biology
Naoyuki Taniguchi, Yuki Ohkawa, Kento Maeda, Yoichiro Harada, Masamichi Nagae, Yasuhiko Kizuka, Hideyuki Ihara, Yoshitaka Ikeda
Summary: Cancer-related changes in glycans on cell surface proteins are regulated by glycosyltransferases and related genes, which play key roles in cancer metastasis and invasion. The significance of EMT and N-glycan branching glycosyltransferases needs to be reconsidered for potential therapeutic strategies. Specific glycosyltransferases involved in EMT or MET pathways may be difficult to define due to their roles in intermediate states.
MOLECULAR ASPECTS OF MEDICINE
(2021)
Article
Medicine, General & Internal
F. Sarpdag, O. Yonem, A. Aktas, Y. Seckin, E. Tuncer, H. Ozer
Summary: The study found that in ulcerative colitis patients, there is a decrease in E-cadherin and an increase in fibronectin. Even during the inactive period, loss of E-cadherin continues. Further studies are needed to confirm the significance of these findings.
BRATISLAVA MEDICAL JOURNAL-BRATISLAVSKE LEKARSKE LISTY
(2021)
Article
Biochemistry & Molecular Biology
Raaj S. Mehta, Jared R. Mayers, Yancong Zhang, Amrisha Bhosle, Nathaniel R. Glasser, Long H. Nguyen, Wenjie Ma, Sena Bae, Tobyn Branck, Kijun Song, Luke Sebastian, Julian Avila Pacheco, Hyuk-Soo Seo, Clary Clish, Sirano Dhe-Paganon, Ashwin N. Ananthakrishnan, Eric A. Franzosa, Emily P. Balskus, Andrew T. Chan, Curtis Huttenhower
Summary: A multi-omics workflow was used to identify the microbial pathways responsible for the degradation of the drug 5-ASA in patients with inflammatory bowel disease. The study found 12 previously uncharacterized microbial acetyltransferases associated with 5-ASA inactivation. In addition, three microbial thiolases and one acyl-CoA N-acyltransferase were found to be epidemiologically associated with an increased risk of treatment failure among 5-ASA users.
Article
Biochemical Research Methods
Florent Clerc, Karli R. Reiding, Noortje de Haan, Carolien A. M. Koeleman, Agnes L. Hipgrave Ederveen, Natalia Manetti, Viktoria Dotz, Vito Annese, Manfred Wuhrer
Summary: This study investigates the associations of immunoglobulin A1 and A2 glycosylation with inflammatory bowel diseases (IBD). Differences in IgA O- and N-glycosylation between patient groups were found to be associated with the diseases, and a statistical model was constructed to predict the disease group of the patients. These findings contribute to the development of noninvasive biomarkers for IBD and improvement in patient care.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Gastroenterology & Hepatology
Yuri Tsujii, Tsutomu Nishida, Naoto Osugi, Yoshifumi Fujii, Aya Sugimoto, Dai Nakamatsu, Kaori Mukai, Kengo Matsumoto, Shiro Hayashi, Masashi Yamamoto, Sachiko Nakajima
Summary: 5-ASA, a crucial drug for UC patients, has various side effects with different severity. Classifying ADRs related to 5-ASA into four groups could facilitate early recognition of ADRs. The study found that fever was the most common ADR, with the first use of 5-ASA being the main trigger.
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Cell Biology
Jiaxi Lu, Deliang Liu, Yuyong Tan, Feihong Deng, Rong Li
Summary: Abnormal immune regulation is a key feature of the pathogenic mechanism of ulcerative colitis, with macrophages and ILC2s playing important roles, particularly in decreased E-cadherin expression. The study found that increased miR-21a-5p expression in peritoneal exosomes correlates negatively with E-cadherin expression, and that miR-21a-5p is derived mainly from M1 macrophages, with KLRG1 promoting excessive ILC2 activation in UC. These findings provide molecular targets and a theoretical basis for understanding and improving the treatment of UC.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Gastroenterology & Hepatology
Sarah C. Sasson, Stephanie M. Slevin, Vincent T. F. Cheung, Isar Nassiri, Anna Olsson-Brown, Eve Fryer, Ricardo C. Ferreira, Dominik Trzupek, Tarun Gupta, Lulia Al-Hillawi, Mari-lenna Issaias, Alistair Easton, Leticia Campo, Michael E. B. FitzPatrick, Joss Adams, Meenali Chitnis, Andrew Protheroe, Mark Tuthill, Nicholas Coupe, Alison Simmons, Miranda Payne, Mark R. Middleton, Simon P. L. Travis, Benjamin P. Fairfax, Paul Klenerman, Oliver Brain
Summary: Our study demonstrates that CD8(+) tissue resident memory T (T-RM) cells are the main activated T cell subset in ICI colitis. The pattern of gastrointestinal immunopathology in ICI colitis is distinct from ulcerative colitis at both the immune and epithelial-signaling levels. Activation of CD8+ T-RM cells correlates with clinical and endoscopic severity of ICI colitis.
Review
Pharmacology & Pharmacy
Alix Demaris, Ella S. K. Widigson, Johan F. K. F. Ilvemark, Casper Steenholdt, Jakob B. Seidelin, Wilhelm Huisinga, Robin Michelet, Linda B. S. Aulin, Charlotte Kloft
Summary: This review aims to analyze the population PK models of infliximab (IFX) in patients with ulcerative colitis (UC) and acute severe UC (ASUC), and assess the impact of disease activity on IFX PK. The results showed that there are still many gaps in the current research, such as a limited number of models specifically developed for UC patients, a lack of studies on severe UC patients, and a lack of evaluation of predictive performance for the models. Therefore, more comprehensive research and adequate reporting and evaluation of the models are needed for clinical application.
Article
Gastroenterology & Hepatology
Natsuki Ishida, Shunya Onoue, Takahiro Miyazu, Satoshi Tamura, Shinya Tani, Mihoko Yamade, Moriya Iwaizumi, Yasushi Hamaya, Satoshi Osawa, Takahisa Furuta, Ken Sugimoto
Summary: This study established a cut-off value of 9.8 for the UCCIS score to predict clinical relapse in patients with ulcerative colitis, and identified optimal cut-off values of 10.2 for UCCIS and 1 for S-MES for predicting relapse within 5 years.
INTERNATIONAL JOURNAL OF COLORECTAL DISEASE
(2021)
Article
Immunology
Ruiqi Guo, Qingyu Meng, Baisen Wang, Fan Li
Summary: In this study, PLD was found to ameliorate DSS-induced colitis by regulating macrophage polarization, indicating its potential as a treatment for colitis. The mechanism behind this effect involves activation of the AMPK pathway.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Plant Sciences
Zhao-Jing Wang, Li-Hua Chen, Jing Xu, Qing-Xia Xu, Wei Xu, Xiu-Wei Yang
Summary: This study aimed to investigate the effects and mechanism of corylin on the gut-brain axis in a mouse model of chronic UC. The results showed that corylin significantly alleviated colitis symptoms, improved the intestinal mucosal barrier and blood-brain barrier, and increased the synthesis of 5-HT in the colon.
Article
Biochemistry & Molecular Biology
Etna Abad, Laia Civit, David Potesil, Zbynek Zdrahal, Alex Lyakhovich
Summary: The growing body of evidence suggests that cancer resistance is driven by a small subset of cancer stem cells, which share common qualities to activate self-defense mechanisms. Rad50, with enhanced DNA damage response, has been identified as a key contributor to tumor cell resistance.
Review
Medical Laboratory Technology
Federico V. Pallardo, Giovanni Pagano, Laura R. Rodriguez, Pilar Gonzalez-Cabo, Alex Lyakhovich, Marco Trifuoggi
Summary: Friedreich's Ataxia is an autosomal recessive genetic disease caused by frataxin deficiency, and research suggests that a combination strategy involving iron chelators, antioxidants, and mitochondrial cofactors may help mitigate the disease progression.
TRANSLATIONAL RESEARCH
(2021)
Article
Oncology
Etna Abad, Sara Samino, Robert L. Grodzicki, Giovanni Pagano, Marco Trifuoggi, Dmitry Graifer, David Potesil, Zbynek Zdrahal, Oscar Yanes, Alex Lyakhovich
Summary: Fanconi anemia is a chromosomal instability disorder associated with aplastic anemia, congenital abnormalities, and a high risk of malignancies. Studies have shown that defective FA cells exhibit various metabolic abnormalities, including increased de novo purine biosynthesis, high concentration of fumarate, and accumulation of purinosomal clusters. These findings suggest a potential role of purine metabolism in oncogenesis in FA cells with impaired DNA damage response.
Review
Cell Biology
Giovanni Pagano, Carla Manfredi, Federico Pallardo, Alex Lyakhovich, Luca Tiano, Marco Trifuoggi
Summary: The mitochondrial cofactors alpha-lipoic acid (ALA), coenzyme Q10 (CoQ10), and carnitine (CARN) play distinct roles in mitochondrial functioning and have strong antioxidant actions. Studies suggest that ALA and CARN are effective in counteracting inflammation-associated redox biomarkers, while CoQ10 decreases in proinflammatory conditions. The use of MNs in acute disorders shows promise, particularly when used in combination to combat oxidative stress.
INFLAMMATION RESEARCH
(2021)
Editorial Material
Gastroenterology & Hepatology
Felix Haller, Christoph Gasche
Review
Biochemistry & Molecular Biology
Giovanni Pagano, Luca Tiano, Federico Pallardo, Alex Lyakhovich, Sudit S. Mukhopadhyay, Paolo Di Bartolomeo, Adriana Zatterale, Marco Trifuoggi
Summary: Fanconi anemia (FA) has been linked to defective DNA repair and proinflammatory condition in early studies, but recent research suggests a potential re-definition of FA as a mitochondrial disease. Studies have shown that FA proteins affect mitochondrial function, indicating a central role of mitochondrial dysfunction in FA. Mitochondrial cofactors may have beneficial effects on FA patients, opening new avenues for potential mitoprotective strategies.
Article
Infectious Diseases
Julia A. Pavlova, Zimfira Z. Khairullina, Andrey G. Tereshchenkov, Pavel A. Nazarov, Dmitrii A. Lukianov, Inna A. Volynkina, Dmitry A. Skvortsov, Gennady I. Makarov, Etna Abad, Somay Y. Murayama, Susumu Kajiwara, Alena Paleskava, Andrey L. Konevega, Yuri N. Antonenko, Alex Lyakhovich, Ilya A. Osterman, Alexey A. Bogdanov, Natalia V. Sumbatyan
Summary: This study synthesized and studied new chimeric compounds that combine chloramphenicol and triphenylphosphonium, showing dual action targeting both bacterial ribosomes and cellular membranes. These compounds demonstrated inhibitory effects on CHL-resistant bacterial strains in addition to suppressing protein synthesis.
Review
Biochemistry & Molecular Biology
Giovanni Pagano, Federico V. Pallardo, Alex Lyakhovich, Luca Tiano, Marco Trifuoggi
Summary: Retinitis pigmentosa is a mitochondrial disease with no current cure, but a combination of mitochondrial nutrients may be effective in delaying progression. Research suggests the need for testing these combinations in animal models to validate potential protective effects against retinal oxidative stress.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Chemistry, Medicinal
Etna Abad, Alex Lyakhovich
Summary: In this study, it was found that extracellular vesicles from chemoresistant TNBC cells can transfer mitochondria to sensitive cancer cells, increasing their chemoresistance. Exosome fractions carrying mitochondria contribute to acquired chemoresistance by increasing mtDNA levels with mutations in the mtND4 gene. Blocking mitochondrial transport by exosome inhibitors can reduce acquired TNBC chemoresistance.
Article
Gastroenterology & Hepatology
Maximilian Baumgartner, Michaela Lang, Hunter Holley, Daniel Crepaz, Bela Hausmann, Petra Pjevac, Doris Moser, Felix Haller, Fabian Hof, Andrea Beer, Elisabeth Orgler, Adrian Frick, Vineeta Khare, Rayko Evstatiev, Susanne Strohmaier, Christian Primas, Werner Dolak, Thomas Koecher, Kristaps Klavins, Timo Rath, Markus F. Neurath, David Berry, Athanasios Makristathis, Markus Muttenthaler, Christoph Gasche
Summary: The study reveals the presence of mucosal biofilms in a subset of patients with IBS and ulcerative colitis, which are associated with disrupted bile acid metabolism and bacterial dysbiosis. This provides new insights into the pathophysiology of IBS and ulcerative colitis.
Article
Pharmacology & Pharmacy
Igor Karp, Alex Lyakhovich
Summary: Traditional cancer treatments kill differentiated cancer cells but not resistant cells or cancer stem cells, which often cause metastasis and recurrences. Unlike many cancers, the bioenergetics of resistant cells and stem cells are often dependent on mitochondrial function. Compounds that induce mitochondrial dysfunction may provide an alternative approach to anticancer therapy.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Immunology
Mario Kuttke, Dominika Hromadova, Ceren Yildirim, Julia S. Brunner, Andrea Vogel, Hannah Paar, Sophie Peters, Maria Weber, Melanie Hofmann, Martina Kerndl, Markus Kieler, Hannes Datler, Laszlo Musiejovsky, Manuel Salzmann, Michaela Lang, Klara Soukup, Angela Halfmann, Omar Sharif, Gernot Schabbauer
Summary: This study found that the PI3K/PTEN signaling pathway in dendritic cells enhances IL-6 production, leading to exacerbated Th1 cell responses and increased mortality in inflammatory bowel diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Nutrition & Dietetics
Annelieke Overbeeke, Michaela Lang, Bela Hausmann, Margarete Watzka, Georgi Nikolov, Jasmin Schwarz, Gudrun Kohl, Kim De Paepe, Kevin Eislmayr, Thomas Decker, Andreas Richter, David Berry
Summary: This study used quantitative analyses to investigate the diet-induced imbalance of mucosal homeostasis. The findings suggest that lack of dietary fiber leads to erosion of the mucus layer due to diminished mucus production rather than overgrowth of mucus degraders. The study also showed reduced intestinal length, loss of the colonic crypt-structure, and decreased diversity in the gut microbiota as a result of fiber deficiency.
Article
Gastroenterology & Hepatology
Maximilian Baumgartner, Rebecca Zirnbauer, Sabine Schlager, Daniel Mertens, Nikolaus Gasche, Barbara Sladek, Craig Herbold, Olga Bochkareva, Vera Emelianenko, Harald Vogelsang, Michaela Lang, Anton Klotz, Birgit Moik, Athanasios Makristathis, David Berry, Stefanie Dabsch, Vineeta Khare, Christoph Gasche
Summary: With increasing urbanization and industrialization, the prevalence of inflammatory bowel diseases (IBDs) has been rising over the past two decades. This study found that the emerging pathogen atypical enteropathogenic E. coli (aEPEC) is associated with disease activity in ulcerative colitis (UC) patients, and it may disrupt immune-microbiota homeostasis.
Article
Gastroenterology & Hepatology
Adrian Frick, Vineeta Khare, Kristine Jimenez, Kyle Dammann, Michaela Lang, Anita Krnjic, Christina Gmainer, Maximilian Baumgartner, Ildiko Mesteri, Christoph Gasche
Summary: The study revealed that PAK1 is involved in regulating crypt homeostasis under inflammatory conditions by controlling Notch1, identifying a novel PAK1-Notch1 axis in the pathophysiology of inflammatory bowel disease and colitis-associated cancer.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Pharmacology & Pharmacy
Paola Orlandi, Marta Banchi, Francesca Vaglini, Marco Carli, Stefano Aringhieri, Arianna Bandini, Carla Pardini, Cristina Viaggi, Michele Lai, Greta Ali, Alessandra Ottani, Eleonora Vandini, Patrizia Guidi, Margherita Bernardeschi, Veronica La Rocca, Giulio Francia, Gabriella Fontanini, Mauro Pistello, Giada Frenzilli, Daniela Giuliani, Marco Scarselli, Guido Bocci
Summary: This study investigates the role of MC4R in melanoma and the use of the selective antagonist ML in combination with vemurafenib. The results show that ML can inhibit melanoma cell proliferation and induce apoptosis through the inhibition of ERK1/2 phosphorylation and reduction of BCL-XL expression. The combination of vemurafenib and ML exhibits a synergistic effect in vitro and inhibits tumor growth in vivo without causing adverse effects.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Conor J. Bloxham, Katina D. Hulme, Fabrizio Fierro, Christian Fercher, Cassandra L. Pegg, Shannon L. O'Brien, Simon R. Foster, Kirsty R. Short, Sebastian G. B. Furness, Melissa E. Reichelt, Masha Y. Niv, Walter G. Thomas
Summary: Bitter taste receptors (T2Rs) are a type of G protein-coupled receptors that allow humans to detect aversive and toxic substances. This study characterized the functional properties of previously identified T2Rs in human cardiac tissues and their naturally occurring polymorphisms. The results showed differences in signaling among different T2R variants, and revealed a potential association between the T2R50 Tyr203 variant and cardiovascular disease.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Lu Chen, Huanying Shi, Wenxin Zhang, Yongjun Zhu, Haifei Chen, Zimei Wu, Huijie Qi, Jiafeng Liu, Mingkang Zhong, Xiaojin Shi, Tianxiao Wang, Qunyi Li
Summary: This study demonstrates that Carfilzomib exhibits potent anti-tumor activity against esophageal squamous cell carcinoma (ESCC) by triggering mitochondrial apoptosis and reprogramming cellular metabolism. It has been identified that activating transcription factor 3 (ATF3) plays a crucial role as a cellular target in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively counteracts the effects of Carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, ATF3 mediates the anti-tumor activity of Carfilzomib, suggesting its potential as a therapeutic agent for ESCC.
BIOCHEMICAL PHARMACOLOGY
(2024)
Review
Pharmacology & Pharmacy
Xing Zhang, Xiang Li, Ran Xia, Hong-Sheng Zhang
Summary: This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer and highlights the role of redox status and metabolism. Combination therapy for ferroptosis has great potential in treating resistant malignant tumors.
BIOCHEMICAL PHARMACOLOGY
(2024)