Article
Neurosciences
Shirley Alteba, Anna Portugalov, Cecilia J. Hillard, Irit Akirav
Summary: Early-life stress and early cannabis use may increase the risk of psychopathologies, affecting behavior in male and female rats. Chronic FAAH inhibition during mid-adolescence did not prevent the long-term effects of ELS on behavior, while it ameliorated ELS-induced depression and anxiety-like behavior during late-adolescence. Sex-dependent alterations in CB1 receptors and GRs expression in the BLA-PFC-CA1 circuit may contribute to the depressive behavioral phenotype.
Article
Biochemistry & Molecular Biology
Chaoling Chen, Weili Wang, Justin L. Poklis, Aron H. Lichtman, Joseph K. Ritter, Gaizun Hu, Dengpiao Xie, Ningjun Li
Summary: The study suggests that FAAH activation and the consequent reduction of AEA contribute to renal fibrogenesis, while FAAH inhibition protects against fibrogenesis in renal cells independently of CB receptors via the AEA-COX-2 pathway.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Shivani Jaiswal, Akhilesh, Ankit Uniyal, Vinod Tiwari, Senthil Raja Ayyannan
Summary: Researchers have discovered a promising lead compound for the treatment of neuropathic pain by designing and synthesizing a series of compounds. The lead compound exhibited potent inhibition activity against both FAAH and MAGL, and showed good safety profile in vivo experiments.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Sanela Rajlic, Luise Surmann, Pia Zimmermann, Christina Katharina Weisheit, Laura Bindila, Hendrik Treede, Markus Velten, Andreas Daiber, Georg Daniel Duerr
Summary: Ischemic cardiomyopathy leads to inflammation and left ventricular dysfunction. Animal studies suggest that the endocannabinoid system may have cardioprotective effects, including cardiomyocyte adaptation, inflammation, and remodeling. This study investigates the potential cardioprotective effect of the endocannabinoid anandamide (AEA) after ischemia and reperfusion using FAAH (-/-) mice and suggests that increased endocannabinoids may have detrimental effects on cardiomyocyte survival due to PPAR-alpha activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Veterinary Sciences
Vikram Thakur, Mohammad Bashashati, Josue Enriquez, Munmun Chattopadhyay
Summary: This study assessed specific gastrointestinal symptoms in Type 1 diabetic mice and evaluated treatment options for this condition. The results showed that inhibiting endocannabinoid degradation may have a therapeutic effect on gastrointestinal dysmotility.
VETERINARY SCIENCES
(2022)
Article
Immunology
Murat Cakir, Ali Aydin, Suat Tekin
Summary: This study investigated the effects of MAGL inhibitor KML29 and FAAH inhibitor URB597 on kidney ischemia-reperfusion injury. The results showed that administration of KML29 and URB597 can reduce kidney damage and inflammation caused by IR. The study suggests that inhibition of MAGL and FAAH may be a new therapeutic strategy for preventing kidney IR injury.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Valerio Chiurchiu, Lucia Scipioni, Beatrice Arosio, Daniela Mari, Sergio Oddi, Mauro Maccarrone
Summary: Growing evidence suggests that the immune system plays a critical role in the pathogenesis and progression of Alzheimer's disease, with targeting peripheral immune mechanisms showing promise as therapeutic strategies. Research has found that in AD patients, there is significantly reduced expression of CB1 and CB2 in B-lymphocytes, and decreased CB2 and increased FAAH in monocytes. Pharmacological inactivation of FAAH in monocytes from AD patients can modulate immune responses by altering cytokine production.
Article
Biochemistry & Molecular Biology
Tiziana Genovese, Andrea Duranti, Ramona D'Amico, Roberta Fusco, Daniela Impellizzeri, Alessio Filippo Peritore, Rosalia Crupi, Enrico Gugliandolo, Salvatore Cuzzocrea, Rosanna Di Paola, Rosalba Siracusa, Marika Cordaro
Summary: Acute lung injury (ALI) is a lung disease characterized by severe inflammation without treatment. This study investigated the role of fatty acid amide hydrolase (FAAH) inhibition in an ALI mouse model and found that it could counteract the inflammatory response and histological changes caused by the disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Sarah Rieck, Sofia Kilgus, Johanna H. Meyer, Hao Huang, Lan Zhao, Michaela Matthey, Xin Wang, Steffen Schmitz-Valckenberg, Bernd K. Fleischmann, Daniela Wenzel
Summary: The study demonstrates that inactivation of FAAH impairs angiogenesis by increasing endogenous anandamide levels, which represents a novel antiangiogenic mechanism. This finding highlights the importance of exploring new pharmacological targets for antiangiogenic therapy in diseases characterized by pathological angiogenesis.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Tiziana Genovese, Andrea Duranti, Francesco Monaco, Rosalba Siracusa, Roberta Fusco, Daniela Impellizzeri, Ramona D'Amico, Marika Cordaro, Salvatore Cuzzocrea, Rosanna Di Paola
Summary: Idiopathic pulmonary fibrosis (IPF), a deadly lung condition, worsens over time and has no known cause. Traditional treatments for IPF, such as corticosteroids and immunomodulatory drugs, often have noticeable side effects and are not very effective. By inhibiting the fatty acid amide hydrolase (FAAH) enzyme, which breaks down endocannabinoids, it is possible to increase the levels of these natural pain-relieving compounds and reduce inflammation. In our study, we used a bleomycin-induced IPF model and found that administering URB878, an FAAH inhibitor, reduced histological changes, cell infiltration, pro-inflammatory cytokine production, inflammation, and nitrosative stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Dorsa Rafiei, Nathan J. Kolla
Summary: Studies have shown that increased FAAH expression is significantly correlated with depressive-like behaviors in animal models, and genetic knockout or pharmacological inhibition of FAAH can effectively reduce these behaviors in a dose-dependent manner. Differences in FAAH expression in depressive-like phenotypes are mainly localized in the animal prefrontal cortex, hippocampus, and striatum. Based on this, FAAH is considered a promising target for developing new pharmacotherapies for Major Depressive Disorder (MDD).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Mahdi Faal Maleki, Hamid Nadri, Mostafa Kianfar, Najmeh Edraki, Farhad Eisvand, Razieh Ghodsi, Seyed Ahmad Mohajeri, Farzin Hadizadeh
Summary: New carbamates were designed as inhibitors of FAAH and ChEs in order to improve the clinical condition of AD patients. Compounds with aminomethyl phenyl linker showed more potent inhibitory activity compared to those with piperazinyl ethyl linker.
BIOORGANIC CHEMISTRY
(2021)
Correction
Neurosciences
J. Kolla Nathan, R. Mizrahi, K. Karas, C. Wang, R. M. Bagby, S. McMain, A. I. Simpson, P. M. Rusjan, R. Tyndale, S. Houle, I. Boileau
Summary: The correction to this paper has been published.
NEUROPSYCHOPHARMACOLOGY
(2021)
Review
Chemistry, Medicinal
Shivani Jaiswal, Senthil Raja Ayyannan
Summary: Recently, FAAH and MAGL inhibitors have attracted attention for their potential anticancer effects. By regulating endogenous ligands, these inhibitors show therapeutic effects in chronic pain, metabolic disorders, psychoses, among others, and exhibit potential in various types of cancers.
Article
Biochemistry & Molecular Biology
Shivani Jaiswal, Senthil Raja Ayyannan
Summary: We designed and synthesized a series of N-1 and C-3 substituted isatin derivatives and found that compound 11 exhibited outstanding FAAH inhibition properties. This compound showed nanomolar-level inhibition and had high blood-brain permeability and significant antioxidant activity.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Matthew J. Roberts, Andrew Morton, Nathan Papa, Anthony Franklin, Sheliyan Raveenthiran, William J. Yaxley, Geoffrey Coughlin, Troy Gianduzzo, Boon Kua, Louise McEwan, David Wong, Brett Delahunt, Lars Egevad, Hemamali Samaratunga, Nicholas Brown, Robert Parkinson, Louise Emmett, John W. Yaxley
Summary: PSMA intensity on PSMA PET/CT is a clinically significant biomarker for predicting oncological outcomes and biochemical recurrence-free survival in patients undergoing radical prostatectomy.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2022)
Letter
Urology & Nephrology
Hemamali Samaratunga, Brett Delahunt, Lars Egevad
Article
Urology & Nephrology
S. Raveenthiran, W. J. Yaxley, T. Franklin, G. Coughlin, M. Roberts, T. Gianduzzo, B. Kua, H. Samaratunga, B. Delahunt, L. Egevad, D. Wong, L. McEwan, N. Brown, R. Parkinson, R. Esler, J. W. Yaxley
Summary: The study aimed to evaluate the ability of mpMRI and PSMA PET/CT individually and in combination to predict tumor location and Gleason score in prostate cancer. The results showed that combining PSMA PET/CT with mpMRI can improve the detection of significant prostate cancer.
JOURNAL OF UROLOGY
(2022)
Article
Pathology
William Yaxley, Brett Delahunt, John Yaxley, Michelle C. Thundeer, Diane N. Kenwright, Lars Egevad, Hemamali Samaratunga
Summary: This study investigated the prognostic value of quantifying the percentage of Gleason pattern 5 tumor in needle biopsies. The results showed that any proportion of Gleason pattern 5 tumor was associated with a worse prognosis compared to GS4+3 tumors.
Article
Immunology
Axel Moeller, Klaus Schwamborn, Adrian Spillmann, Janet Hoogstraate, Robert Szulkin, Olof Akre, Lars Egevad, Mark Clements, Markus Aly
Summary: Repurposing existing drugs and vaccines for different diseases shows promise. A study found that oral cholera vaccine could potentially be used to treat inflammatory diseases and common cancers. However, the observed effect may be due to a bias in healthy travelers.
Article
Pathology
Kimmo Kartasalo, Peter Strom, Pekka Ruusuvuori, Hemamali Samaratunga, Brett Delahunt, Toyonori Tsuzuki, Martin Eklund, Lars Egevad
Summary: This study developed an artificial intelligence algorithm based on deep neural networks for detecting perineural invasion (PNI) in prostate biopsies. By digitizing and annotating a large number of biopsy samples, the algorithm achieved high accuracy in PNI detection, potentially providing valuable assistance to pathologists.
Article
Biochemical Research Methods
Philippe Weitz, Yinxi Wang, Kimmo Kartasalo, Lars Egevad, Johan Lindberg, Henrik Gronberg, Martin Eklund, Mattias Rantalainen
Summary: This study proposes a new approach to predict gene expression profiles based on the morphological features of tumors. By using convolutional neural networks, gene expression profiles were successfully predicted from hematoxylin and eosin-stained images, offering a cost-effective solution for large-scale research studies and molecular diagnostics.
Letter
Pathology
Hemamal Samaratunga, Tony Gianduzzo, Joanna Perry-Keene, Lars Egevad, Brett Delahunt
Article
Cell Biology
Lars Egevad, Brett Delahunt, Kenneth A. Iczkowski, Theo van der Kwast, Geert J. L. H. van Leenders, Katia R. M. Leite, Chin-Chen Pan, Hemamali Samaratunga, Toyonori Tsuzuki, Nita Mulliqi, Xiaoyi Ji, Henrik Olsson, Masi Valkonen, Pekka Ruusuvuori, Martin Eklund, Kimmo Kartasalo
Summary: There is evidence that cribriform morphology is associated with a worse prognosis for prostatic adenocarcinoma. This study aimed to investigate the reproducibility of cribriform cancer diagnosis in prostate needle biopsies. A panel of nine prostate pathology experts independently reviewed 304 digitised biopsies and achieved a 2/3 consensus diagnosis of cribriform and noncribriform cancer in 90% of the cases. Strict diagnostic criteria were used to identify cribriform patterns and generate a set of consensus cases for standardization.
Article
Medicine, General & Internal
M. Alvaro Berbis, David S. McClintock, Andrey Bychkov, Jeroen Van der Laak, Liron Pantanowitz, Jochen K. Lennerz, Jerome Y. Cheng, Brett Delahunt, Lars Egevad, Catarina Eloy, Alton B. Farris III, Filippo Fraggetta, Raimundo Garcia del Moral, Douglas J. Hartman, Markus D. Herrmann, Eva Hollemans, Kenneth A. Iczkowski, Aly Karsan, Mark Kriegsmann, Mohamed E. Salama, John H. Sinard, J. Mark Tuthill, Bethany Williams, Cesar Casado-Sanchez, Victor Sanchez-Turrion, Antonio Luna, Jose Aneiros-Fernandez, Jeanne Shen
Summary: AI is expected to be routinely and impactfully used in pathology practice by 2030, according to experts in the field. This consensus study highlights the anticipated short-to-mid-term impact of AI and raises important practical, ethical, and legal challenges that need to be addressed prior to its clinical implementation.
Article
Oncology
Naveen S. Vasudev, Ghislaine Scelo, Kate I. Glennon, Michelle Wilson, Louis Letourneau, Robert Eveleigh, Nazanin Nourbehesht, Madeleine Arseneault, Antoine Paccard, Lars Egevad, Juris Viksna, Edgars Celms, Sharon M. Jackson, Behnoush Abedi-Ardekani, Anne Y. Warren, Peter J. Selby, Sebastian Trainor, Michael Kimuli, Jon Cartledge, Naeem Soomro, Adebanji Adeyoju, Poulam M. Patel, Magdalena B. Wozniak, Ivana Holcatova, Antonin Brisuda, Vladimir Janout, Estelle Chanudet, David Zaridze, Anush Moukeria, Oxana Shangina, Lenka Foretova, Marie Navratilova, Dana Mates, Viorel Jinga, Ljiljana Bogdanovic, Bozidar Kovacevic, Anne Cambon-Thomsen, Guillaume Bourque, Alvis Brazma, Jorg Tost, Paul Brennan, Mark Lathrop, Yasser Riazalhosseini, Rosamonde E. Banks
Summary: Targeted gene sequencing can help in risk prediction and adjuvant treatment decisions for patients with resected localized ccRCC. Mutations in the VHL gene have a significant impact on patient outcomes, independent of other gene mutations. Genomic characterization can personalize treatment discussions and inform future adjuvant trial design.
CLINICAL CANCER RESEARCH
(2023)
Editorial Material
Pathology
Murali Varma, Brett Delahunt, Liang Cheng, Runjan Chetty, Eva Comperat, Vikram Deshpande, Lars Egevad, Theodorus H. van der Kwast, Antonio Lopez-Beltran, W. Glenn McCluggage
JOURNAL OF CLINICAL PATHOLOGY
(2023)
Article
Toxicology
Lina Thors, Elisabeth Wigenstam, Johanna Qvarnstrom, Andreas Larsson, Sandra Lindberg, Linda Oberg, Jenny Rattfelt-Nyholm, Anders Bucht
Summary: Decontamination is crucial in mass casualty incidents to prevent the absorption of toxic compounds. This study evaluated different decontamination strategies for skin exposure to various contaminants, finding that efficacy depended on the specific chemical involved. Dry removal followed by wet decontamination was beneficial for sulfur mustard simulant exposure, while rapid wet decontamination was more effective for industrial chemical and nerve agent exposure. However, wet decontamination procedures resulted in increased penetration of the nerve agent VX. In conclusion, establishing simple and efficient decontamination procedures for a wide range of chemicals is challenging, and including a dry removal step can be agent-specific and facilitate patient management.
TOXICOLOGY IN VITRO
(2023)
Letter
Pathology
Hemamali Samaratunga, Lars Egevad, Brett Delahunt
Review
Pathology
Murali Varma, Laura C. Collins, Runjan Chetty, Dipti M. Karamchandani, Karen Talia, John Dormer, Monika Vyas, Brendan Conn, Yaileen D. Guzman-Arocho, Adam Jones, Miranda Pring, W. Glenn Mccluggage
Summary: This paper highlights the importance of macroscopic examination and tissue sampling in histopathology reporting and discusses potential solutions and challenges. It emphasizes the need for adequate guidance and supervision in macroscopic examination and highlights the importance of clinical context, specimen fixation, macroscopic descriptions, and tissue sampling.
JOURNAL OF CLINICAL PATHOLOGY
(2023)