Article
Gastroenterology & Hepatology
Debjyoti Kundu, Lindsey Kennedy, Tianhao Zhou, Burcin Ekser, Vik Meadows, Amelia Sybenga, Konstantina Kyritsi, Lixian Chen, Ludovica Ceci, Nan Wu, Chaodong Wu, Shannon Glaser, Guido Carpino, Paolo Onori, Eugenio Gaudio, Gianfranco Alpini, Heather Francis
Summary: Inhibiting hepatic p16 expression may be a therapeutic approach for improving NAFLD/NASH phenotypes.
Article
Biochemistry & Molecular Biology
Alexander Mordhorst, Priyavathi Dhandapani, Susann Matthes, Valentina Mosienko, Michael Rothe, Mihail Todiras, Julie Self, Wolf-Hagen Schunck, Anja Schutz, Michael Bader, Natalia Alenina
Summary: Serotonin synthesis involves the hydroxylation of tryptophan, with most vertebrates having two known enzymes for this step. However, even in animals lacking these two enzymes, there is still some serotonin production, suggesting the presence of a third enzyme. The study found evidence that phenylalanine hydroxylase (PAH) may act as a third tryptophan hydroxylase in mammals, contributing to serotonin levels in the blood and potentially serving as a local source of serotonin in organs where other TPHs are not expressed.
Article
Biochemistry & Molecular Biology
Suvarna H. Pagire, Haushabhau S. Pagire, Kun-Young Park, Eun Jung Bae, Kwang-eun Kim, Minhee Kim, Jihyeon Yoon, Saravanan Parameswaran, Jun-Ho Choi, Sungmi Park, Jae-Han Jeon, Jin Sook Song, Myung Ae Bae, In-Kyu Lee, Hail Kim, Jae Myoung Suh, Jin Hee Ahn
Summary: This article introduces a new tryptophan hydroxylase type I (TPH1) inhibitor that acts in peripheral tissues for treating obesity and fatty liver disease. The inhibitor exhibits good in vitro activity and liver microsomal stability, while not penetrating the blood-brain barrier.
Article
Multidisciplinary Sciences
Nimish Godbole, Iiris Nyholm, Maria Hukkinen, Joseph R. Davidson, Athanasios Tyraskis, Jouko Lohi, Paivi Heikkila, Katja Eloranta, Marjut Pihlajoki, Mark Davenport, Markku Heikinheimo, Antti Kyronlahti, Mikko P. Pakarinen
Summary: This study investigates the utility of secretin receptor (SCTR) as a potential biomarker for predicting native liver survival and clearance of jaundice after portoenterostomy (PE) surgery in patients with biliary atresia (BA). The results show that higher expression of SCTR is associated with lower 5-year native liver survival and clearance of jaundice after PE. SCTR expression also correlates with liver fibrosis, ductular reaction, and markers of fibrosis and cholangiocytes. Therefore, SCTR may serve as a promising prognostic marker for PE outcomes and liver injury in BA.
SCIENTIFIC REPORTS
(2022)
Article
Gastroenterology & Hepatology
Binu John, Gabriella Aitcheson, Kaley B. Schwartz, Nidah S. Khakoo, Bassam Dahman, Yangyang Deng, David Goldberg, Paul Martin, Tamar H. Taddei, Cynthia Levy, David E. Kaplan
Summary: In patients with PBC and well-compensated cirrhosis, male sex is associated with a higher risk of both death and liver-related death or transplantation.
Article
Multidisciplinary Sciences
Naqash Alam, Sadiq Ali, Nazia Akbar, Muhammad Ilyas, Habib Ahmed, Arooj Mustafa, Shehzada Khurram, Zeeshan Sajid, Najeeb Ullah, Shumaila Qayyum, Tariq Rahim, Mian Syed Usman, Nawad Ali, Imad Khan, Khola Pervez, BiBi Sumaira, Nasir Ali, Nighat Sultana, Adeel Yunus Tanoli, Madiha Islam
Summary: This study aimed to investigate the association between single nucleotide polymorphisms in 6 candidate genes linked to the neurobiology of major depressive disorder in the North-Western population of Pakistan, but no statistically significant correlation was observed. The research did not support the major role of these polymorphisms in contributing to MDD susceptibility.
Article
Biochemistry & Molecular Biology
Ying Wan, Tianhao Zhou, Elise Slevin, Sachiko Koyama, Xuedong Li, Kelly Harrison, Tian Li, Bingru Zhou, Sugeily Ramos Lorenzo, Yudian Zhang, Wenjuan Xu, James E. Klaunig, Chaodong Wu, Ashok K. Shetty, Chiung-Kuei Huang, Fanyin Meng
Summary: Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by cholestasis, inflammation, and fibrotic scar formation. This study investigated the role of liver-specific microRNA-34a in ductular reaction and liver fibrosis. They found that miR-34a expression was increased in PSC livers, and its knockout in a cholestatic liver disease model reduced ductular pathology and fibrotic responses.
Article
Biochemistry & Molecular Biology
Xinjie Shi, Guiyun Zhao, Hu Li, Zhijie Zhao, Wei Li, Miaolian Wu, Yi-Ling Du
Summary: The authors have identified a new class of tryptophan hydroxylases in bacteria, which are mechanistically distinct from their eukaryotic counterparts and can be used for the synthesis of melatonin.
NATURE CHEMICAL BIOLOGY
(2023)
Review
Immunology
Yushu Yang, XiaoSong He, Manuel Rojas, Patrick S. C. Leung, Lixia Gao
Summary: Primary biliary cholangitis (PBC) is an immune-mediated liver disease characterized by cholestasis, biliary injuries, liver fibrosis, and chronic non-suppurative cholangitis. The pathogenesis of PBC involves immune dysregulation, abnormal bile metabolism, and progressive fibrosis, leading to cirrhosis and liver failure. Current treatments have limitations, and there is a need for further research to investigate underlying mechanisms and develop more effective therapies.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Cell Biology
Luigi Aloia
Summary: The adult liver has crucial functions and a high regenerative potential. The spatial organization of liver compartments plays a key role in liver regeneration. YAP/TAZ transcriptional co-activators regulate liver regeneration and liver disease by sensing extracellular matrix, metabolic and epigenetic remodeling.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Atae Akhrif, Marcel Romanos, Katharina Peters, Ann-Kathrin Furtmann, Julian Caspers, Klaus-Peter Lesch, Eva M. Meisenzahl-Lechner, Susanne Neufang
Summary: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that often persists into adulthood. In this study, the interaction of genetic and environmental factors in causing ADHD symptoms, such as impulsivity, was investigated. The TPH2 gene and DNA methylation in the 5' untranslated region of TPH2 were found to be associated with brain activity and behavioral performance in ADHD patients. This study provides insights into how genetic and epigenetic factors contribute to ADHD and impulsivity.
Article
Medicine, General & Internal
Nimish Godbole, Iiris Nyholm, Maria Hukkinen, Joseph R. Davidson, Athanasios Tyraskis, Katja Eloranta, Noora Andersson, Jouko Lohi, Paivi Heikkila, Antti Kyronlahti, Marjut Pihlajoki, Mark Davenport, Markku Heikinheimo, Mikko P. Pakarinen
Summary: This study revealed that IL-8 is overexpressed in the liver and serum of biliary atresia patients, especially during the postoperative period. IL-8 expression is positively correlated with ductular reaction, liver fibrogenesis, and related cellular markers.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Medicine, Research & Experimental
Jie Wang, Zihang Yuan, Haoran Zhang, Qipeng Wu, Yingying Miao, Yunxia Xu, Qinwei Yu, Xiaofei Huang, Ziling Zhang, Xinliang Huang, Qianhui Tang, Luyong Zhang, Zhenzhou Jiang
Summary: The study revealed that OCA induced overexpression of OPN in the liver of BDL mice, exacerbating ductular reaction, fibrosis, and liver inflammation, while reducing hepatocyte proliferation. This mechanism helps explain the risk of liver damage associated with OCA.
Article
Biochemistry & Molecular Biology
Vanessa Bottino-Rojas, Igor Ferreira-Almeida, Rodrigo D. Nunes, Xuechun Feng, Thai Binh Pham, Adam Kelsey, Rebeca Carballar-Lejarazu, Valentino Gantz, Pedro L. Oliveira, Anthony A. James
Summary: Mutations in the ommochrome biosynthesis pathway have varying effects on the survival and reproduction of mosquitoes, as well as compromising the permeability barrier function of the midgut in some species. Surprisingly, these mutations lead to an increase in microbiota without a general induction of immune genes. Antibiotic treatment can rescue some deleterious traits, and supplementation of xanthurenic acid can limit microbiota proliferation. These findings are important for the development of genetic strategies targeting vector mosquitoes.
INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2022)
Article
Neurosciences
Mariana Angoa-Perez, Branislava Zagorac, Dina M. Francescutti, Kevin R. Theis, Donald M. Kuhn
Summary: Neuronal 5HT plays a significant role in stress-related responses, including influencing food intake, body weight, CORT levels, and the gut microbiome, but has minimal effects on the brain and adrenal responses induced by CORT.
Article
Clinical Neurology
Nazar Serikuly, Erik T. Alpyshov, DongMei Wang, JingTao Wang, LongEn Yang, GuoJun Hu, DongNi Yan, Konstantin A. Demin, Tatyana O. Kolesnikova, David Galstyan, Tamara G. Amstislavskaya, Abdrazak M. Babashev, Mikael S. Mor, Evgeniya Efimova, Raul R. Gainetdinov, Tatyana Strekalova, Murilo S. de Abreu, Cai Song, Allan Kalueff
Summary: Arecoline is a naturally occurring psychoactive alkaloid with effects on nicotinic and muscarinic receptors. Studies on zebrafish showed that acute and chronic arecoline treatments induced anxiolytic-like behavior, altered neurotransmitter levels, and activated specific genes related to brain function and immune response, suggesting potential for developing novel anxiolytic drugs based on arecoline-like molecules.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2021)
Article
Neurosciences
Evgeniya V. Efimova, Alena A. Kozlova, Valeria Razenkova, Nataliia V. Katolikova, Kristina A. Antonova, Tatyana D. Sotnikova, Natalia S. Merkulyeva, Aleksandr S. Veshchitskii, Daria S. Kalinina, Dmitry E. Korzhevskii, Pavel E. Musienko, Evgeny V. Kanov, Raul R. Gainetdinov
Summary: TAAR5 is not only involved in the regulation of emotional status, but also adult neurogenesis and dopamine transmission. TAAR5-KO mice showed an increased number of proliferating neurons in the major neurogenic areas, suggesting that future TAAR5 antagonists may provide new treatment opportunities for neurodegenerative disorders like Parkinson's disease.
Article
Clinical Neurology
Anastasia Levchenko, Alexander Kanapin, Anastasia Samsonova, Olga Yu. Fedorenko, Elena G. Kornetova, Timur Nurgaliev, Galina E. Mazo, Arkadiy V. Semke, Alexander O. Kibitov, Nikolay A. Bokhan, Raul R. Gainetdinov, Svetlana A. Ivanova
Summary: In this study, a genome-wide association study was conducted in a cohort of paranoid schizophrenia patients with tardive dyskinesia and healthy controls, revealing a gene network associated with neurodevelopment and brain function. The findings suggest common pathogenic mechanisms for schizophrenia and tardive dyskinesia, indicating that orofacial and limbtruncal types of tardive dyskinesia might be driven by interacting genes implicated in neurodevelopment. The results shed light on the importance of neurodevelopment and brain function in these disorders.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Junwan Fan, Haowen Li, Lun Kuang, Zichen Zhao, Wenyan He, Chen Liu, Yongjun Wang, Steven Y. Cheng, Wei Chen
Summary: A new Smoothened inhibitor, 0025A, has been discovered in this study, which effectively targets the Hedgehog signaling pathway and inhibits cancer cell activity. Additionally, it can suppress hair growth in mice.
CELL AND BIOSCIENCE
(2021)
Article
Neurosciences
Alexander Lopachev, Maria A. Lagarkova, Olga S. Lebedeva, Margarita A. Ezhova, Rogneda B. Kazanskaya, Yulia A. Timoshina, Anastasiya Khutorova, Evgeny E. Akkuratov, Tatiana N. Fedorova, Raul R. Gainetdinov
Summary: Cardiotonic steroids can induce significant changes in gene expression in neurons, leading to the activation of pathways associated with neuronal maturation and synapse formation. This activation is achieved through the MAP-kinase ERK1/2 and the transcriptional factor CREB. These findings suggest that ouabain at non-toxic concentrations may promote neuronal maturation, neurite growth, and increased synaptogenesis in dopamine-receptive GABAergic neurons.
Article
Biochemistry & Molecular Biology
Placido Illiano, Damiana Leo, Raul R. Gainetdinov, Marta Pardo
Summary: The study focuses on the PFC function in early adolescent female rats with heterozygous and homozygous ablation of DAT, showing changes in neuronal and glial cell homeostasis. Genetic ablation of DAT in the early adolescent PFC leads to a hyperactive phenotype, alterations in glutamatergic neurotransmission, neurodegeneration, and glial activation. This study provides insight into neuroinflammatory pathological processes in DAT-ablated female rats, potentially offering new investigational approaches in human diseases.
Article
Biochemistry & Molecular Biology
Ramilya Z. Murtazina, Ilya S. Zhukov, Olga M. Korenkova, Elena A. Popova, Savelii R. Kuvarzin, Evgeniya V. Efimova, Larisa G. Kubarskaya, Ekaterina G. Batotsyrenova, Ekaterina A. Zolotoverkhaya, Anastasia N. Vaganova, Sergey A. Apryatin, Natalia V. Alenina, Raul R. Gainetdinov
Summary: The study found no significant effects of TAAR9 on hematological and most biochemical parameters, but revealed a significant decrease in total and low-density lipoprotein cholesterol levels in the blood of TAAR9-KO rats. This suggests a potential new drug target for disorders related to cholesterol regulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Behavioral Sciences
Natalia P. Kurzina, Anna B. Volnova, Irina Y. Aristova, Raul R. Gainetdinov
Summary: ADHD is believed to be related to increased hyperactivity caused by alterations in dopamine transmission. DAT-KO rats, a model for studying ADHD-related mechanisms, were found to have deficiencies in cognitive task learning, but their hyperactivity did not hinder learning non-spatial tasks with novel stimuli. The longer exploration of novel objects in DAT-KO rats may facilitate persistent learning in the task paradigm.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2021)
Article
Pharmacology & Pharmacy
Stephen P. H. Alexander, Arthur Christopoulos, Anthony P. Davenport, Eamonn Kelly, Alistair Mathie, John A. Peters, Emma L. Veale, Jane F. Armstrong, Elena Faccenda, Simon D. Harding, Adam J. Pawson, Christopher Southan, Jamie A. Davies, Maria Pia Abbracchio, Wayne Alexander, Khaled Al-hosaini, Magnus Baeck, Nicholas M. Barnes, Ross Bathgate, Jean-Martin Beaulieu, Kenneth E. Bernstein, Bernhard Bettler, Nigel J. M. Birdsall, Victoria Blaho, Francois Boulay, Corinne Bousquet, Hans Braeuner-Osborne, Geoffrey Burnstock, Girolamo Calo, Justo P. Castano, KevinJ Catt, Stefania Ceruti, Paul Chazot, Nan Chiang, Bice Chini, Jerold Chun, Antonia Cianciulli, Olivier Civelli, Lucie H. Clapp, Rejean Couture, Zsolt Csaba, Claes Dahlgren, Gordon Dent, Khuraijam Dhanachandra Singh, Steven D. Douglas, Pascal Dournaud, Satoru Eguchi, Emanuel Escher, Edward J. Filardo, Tung Fong, Marta Fumagalli, Raul R. Gainetdinov, Marc de Gasparo, Craig Gerard, Marvin Gershengorn, Fernand Gobeil, Theodore L. Goodfriend, Cyril Goudet, Karen J. Gregory, Andrew L. Gundlach, Joerg Hamann, Julien Hanson, Richard L. Hauger, Debbie L. Hay, Akos Heinemann, Morley D. Hollenberg, Nicholas D. Holliday, Mastgugu Horiuchi, Daniel Hoyer, Laszlo Hunyady, Ahsan Husain, Adriaan P. IJzerman, Tadashi Inagami, Kenneth A. Jacobson, Robert T. Jensen, Ralf Jockers, Deepa Jonnalagadda, Sadashiva Karnik, Klemens Kaupmann, Jacqueline Kemp, Charles Kennedy, Yasuyuki Kihara, Takio Kitazawa, Pawel Kozielewicz, Hans-Juergen Kreienkamp, Jyrki P. Kukkonen, Tobias Langenhan, Katie Leach, Davide Lecca, John D. Lee, Susan E. Leeman, Jerome Leprince, Xaria X. Li, Tom Lloyd Williams, Stephen J. Lolait, Amelie Lupp, Robyn Macrae, Janet Maguire, Jean Mazella, Craig A. McArdle, Shlomo Melmed, Martin C. Michel, Laurence J. Miller, Vincenzo Mitolo, Bernard Mouillac, Christa E. Mueller, Philip Murphy, Jean-Louis Nahon, Tony Ngo, Xavier Norel, Duuamene Nyimanu, Anne-Marie Ocarroll, Stefan Offermanns, Maria Antonietta Panaro, Marc Parmentier, Roger G. Pertwee, Jean-Philippe Pin, Eric R. Prossnitz, Mark Quinn, Rithwik Ramachandran, Manisha Ray, Rainer K. Reinscheid, Philippe Rondard, G. Enrico Rovati, Chiara Ruzza, Gareth J. Sanger, Torsten Schoeneberg, Gunnar Schulte, Stefan Schulz, Deborah L. Segaloff, Charles N. Serhan, Leigh A. Stoddart, Yukihiko Sugimoto, Roger Summers, Valerie P. Tan, David Thal, Walter (Wally) Thomas, PieterB M. W. M. Timmermans, Kalyan Tirupula, Giovanni Tulipano, Hamiyet Unal, Thomas Unger, Celine Valant, Patrick Vanderheyden, David Vaudry, Hubert Vaudry, Jean-Pierre Vilardaga, Christopher S. Walker, Ji Ming Wang, Donald T. Ward, Hans-Juergen Wester, Gary B. Willars, Trent M. Woodruff, Chengcan Yao, Richard D. Ye
Summary: The Concise Guide to PHARMACOLOGY 2021/22 presents concise overviews of nearly 1900 human drug targets with an emphasis on selective pharmacology, along with links to a more detailed knowledgebase. It serves as a permanent, citable record for researchers, providing useful information in the field of pharmacology.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Cell Biology
Alena A. Kozlova, Vinitha N. Ragavan, Natalia Jarzebska, Iana V. Lukianova, Anastasia E. Bikmurzina, Elena Rubets, Toshiko Suzuki-Yamamoto, Masumi Kimoto, Arduino A. Mangoni, Raul R. Gainetdinov, Norbert Weiss, Michael Bauer, Alexander G. Markov, Roman N. Rodionov, Nadine Bernhardt
Summary: The distribution of ADMA and DDAH systems in the brain is of significant importance, with DDAH1 found to be widely distributed among various cell types, while DDAH2 is limited to a few brain regions and neurons.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anastasia N. Vaganova, Ramilya Z. Murtazina, Taisiia S. Shemyakova, Andrey D. Prjibelski, Nataliia Katolikova, Raul R. Gainetdinov
Summary: TAAR5 receptors not only participate in odor perception but also express in brain structures, potentially related to emotional behaviors and pathogenesis of brain disorders. Research has found ubiquitous low expression of TAAR5 in various brain regions and altered expression in diseases such as Down syndrome and depression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Ilya S. Zhukov, Larisa G. Kubarskaya, Inessa Karpova, Anastasia N. Vaganova, Marina N. Karpenko, Raul R. Gainetdinov
Summary: Trace amine-associated receptor 5 (TAAR5) plays a crucial role in perceiving odors, regulating emotions, and potentially treating neuropsychiatric disorders. Research suggests that TAAR5 deficiency may lead to minor negative effects on hematological parameters, while having minimal impact on other blood-related factors. Further study is needed to fully understand the implications of TAAR5 gene knockout in erythropoiesis and eryptosis processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Alexander Sapegin, Anatoly A. Peshkov, Evgeny Kanov, Raul R. Gainetdinov, Beata Duszynska, Andrzej J. Bojarski, Mikhail Krasavin
Summary: Di(het)areno-fused 1,4,7-(oxa)thiadiazecanes were synthesized via the 'hydrated imidazoline ring expansion' (HIRE) method, with two compounds displaying micromolar agonistic activity towards TAAR1. These compounds are suitable as scaffolds for the design of selective aminergic receptor modulators.
MENDELEEV COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Stefan R. Bornstein, Karin Voit-Bak, Timo Donate, Roman N. Rodionov, Raul R. Gainetdinov, Sergey Tselmin, Waldemar Kanczkowski, Gregor M. Mueller, Martin Achleitner, Jun Wang, Julio Licinio, Michael Bauer, Allan H. Young, Sandrine Thuret, Nicole Bechmann, Richard Straube
Summary: Research has found that patients with long COVID syndrome and chronic fatigue syndrome have similar elevation of autoantibodies. Extracorporeal apheresis can effectively reduce these antibodies levels and improve symptoms, providing a promising therapeutic option for patients with post-COVID-19 syndrome. This method may also be effective in cases involving other unknown antibodies and inflammatory mediators.
MOLECULAR PSYCHIATRY
(2022)
Article
Clinical Neurology
Alena A. Kozlova, Elena Rubets, Magdalini R. Vareltzoglou, Natalia Jarzebska, Vinitha N. Ragavan, Yingjie Chen, Jens Martens-Lobenhoffer, Stefanie M. Bode-Boeger, Raul R. Gainetdinov, Roman N. Rodionov, Nadine Bernhardt
Summary: In this study, the role of DDAH1 in behavioral endophenotypes with neuropsychiatric relevance was investigated. The results showed that DDAH1-ko mice exhibited changes in exploratory behavior, amphetamine response, and dopamine metabolite levels. Female mice showed the most significant amphetamine response, supporting the potential implication of the DDAH/ADMA pathway in central nervous system processes.
JOURNAL OF NEURAL TRANSMISSION
(2023)