Article
Engineering, Biomedical
Alexander Stahl, Dake Hao, Janos Barrera, Dominic Henn, Sien Lin, Seyedsina Moeinzadeh, Sungwoo Kim, William Maloney, Geoffrey Gurtner, Aijun Wang, Yunzhi Peter Yang
Summary: Conventional synthetic vascular grafts have high failure rates due to mismatched mechanical properties with native vessels and poor regenerative potential. In this study, we developed a new bioactive synthetic vascular graft with tailored pore sizes to promote pro-regenerative macrophage populations and improve vascular regeneration. The grafts showed similar mechanical properties to native blood vessels and maintained patency and vascular regeneration in animal models.
BIOACTIVE MATERIALS
(2023)
Article
Biochemistry & Molecular Biology
Yann Ayotte, Eve Bernet, Francois Bilodeau, Mena Cimino, Dominic Gagnon, Marthe Lebughe, Maxime Mistretta, Paul Ogadinma, Sarah-Lisa Ouali, Aissatou Aicha Sow, Laurent Chatel-Chaix, Albert Descoteaux, Giulia Manina, Dave Richard, Frederic Veyrier, Steven R. LaPlante
Summary: Fragment-based lead discovery has been proven to be a powerful technique for identifying starting chemical matter to target specific proteins or nucleic acids. The study successfully applied phenotype cell-based screens using a curated fragment library to identify inhibitors against a range of pathogens, showing that fragment-based phenotypic lead discovery is a promising complementary approach for tackling infectious diseases and other drug-discovery programs.
ACS CHEMICAL BIOLOGY
(2021)
Article
Cell Biology
Shadi A. D. Mohammed, Hanxing Liu, Salem Baldi, Pingping Chen, Fang Lu, Shumin Liu
Summary: This study found that Gedan Jiangya decoction (GJD) has therapeutic effects on spontaneously hypertensive rats (SHR) by lowering blood pressure, improving cardiovascular remodeling, and reducing inflammation.
MEDIATORS OF INFLAMMATION
(2022)
Article
Biochemistry & Molecular Biology
Tatsuo Akaki, Yuki Bessho, Takashi Ito, Shingo Fujioka, Minoru Ubukata, Genki Mori, Kenji Yamanaka, Takuya Orita, Satoki Doi, Tomoko Iwanaga, Kazutaka Ikegashira, Yoshiji Hantani, Isao Nakanishi, Tsuyoshi Adachi
Summary: This study utilized a fragment-based lead discovery approach to identify inhibitors against PDHKs with novel chemotypes, providing new structural insights into the deep binding interactions at the ATP site. The research successfully generated lead compounds with high selectivity and efficiency, opening up a new direction for the development of PDHKs inhibitors.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Daniel Evans-Yamamoto, Francois D. Rouleau, Piyush Nanda, Koji Makanae, Yin Liu, Philippe C. Despres, Hitoshi Matsuo, Motoaki Seki, Alexandre K. Dube, Diana Ascencio, Nozomu Yachie, Christian R. Landry
Summary: Barcode fusion genetics (BFG) utilizes deep sequencing to improve the throughput of protein-protein interaction (PPI) screening. This technology expands the scope of PPI research by leveraging clone collections from any species of interest and demonstrates high sensitivity and specificity for capturing known interactions.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Nutrition & Dietetics
Christopher H. Rhodes, Chenghao Zhu, Joanne Agus, Xinyu Tang, Qianyan Li, JoAnne Engebrecht, Angela M. Zivkovic
Summary: Periodic prolonged fasting (PF) extends lifespan and improves disease states through modulating the immune system. However, the relationship between metabolic factors, immunity, and longevity during PF in humans is poorly understood. This study aimed to investigate the effects of PF on metabolic and immune health in human subjects and identify plasma-borne factors responsible for these effects.
AMERICAN JOURNAL OF CLINICAL NUTRITION
(2023)
Article
Biochemistry & Molecular Biology
Hendrik J. Brink, Rick Riemens, Stephanie Thee, Berend Beishuizen, Daniel da Costa Pereira, Maikel Wijtmans, Iwan de Esch, Martine J. Smit, Albertus H. de Boer
Summary: In this study, a fragment-based drug screening approach was used to identify a PPI stabilizer targeting 14-3-3. The stabilizer was found to cooperatively stabilize 14-3-3 and enhance its binding to client proteins. This finding provides a tool compound for investigating the interactions between 14-3-3 and client proteins.
Article
Biochemistry & Molecular Biology
Wolf-Stephan Rudi, Michael Molitor, Venkata Garlapati, Stefanie Finger, Johannes Wild, Thomas Muenzel, Susanne H. Karbach, Philip Wenzel
Summary: The study shows that early treatment with the ACE inhibitor ramipril after myocardial infarction can reduce cardiac and circulating inflammation, improve retention of hematopoietic precursor cells in the bone marrow, and increase survival rates. Long-term ACE inhibition also limits vascular inflammation and improves endothelial function in mice with ischemic heart failure.
Article
Chemistry, Medicinal
Satish Sagar, Sarbjit Singh, Jayapal Reddy Mallareddy, Yogesh A. Sonawane, John Napoleon, Sandeep Rana, Jacob Contreras, Christabelle Rajesh, Edward L. Ezell, Smitha Kizhake, Jered C. Garrison, Prakash Radhakrishnan, Amarnath Natarajan
Summary: A novel quinoxaline urea analog 84 was discovered to inhibit TNF alpha-induced NF kappa B and pancreatic cancer cell growth to a greater extent than the previously studied 13-197. Analog 84 exhibited higher potency and oral bioavailability compared to 13-197.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Cardiac & Cardiovascular Systems
Michael R. Jackson, Kristie D. Cox, Simon D. P. Baugh, Luke Wakeen, Adel A. Rashad, Patrick Y. S. Lam, Boris Polyak, Marilyn Schuman Jorns
Summary: This study aims to discover and evaluate a first-in-class inhibitor of human sulfide:quinone oxidoreductase (SQOR) for the treatment of heart failure patients with reduced ejection fraction (HFrEF). The researchers identified a potent inhibitor (STI1) through high-throughput screening and demonstrated that it had a cardioprotective effect in an animal model of HFrEF. Treated mice showed reduced cardiac damage and improved survival, indicating the potential of SQOR inhibitors as a novel therapeutic approach for HFrEF.
CARDIOVASCULAR RESEARCH
(2022)
Article
Chemistry, Physical
Fan Zhang, Hui Tao, Jessica M. Gluck, Lu Wang, Mani A. Daneshmand, Martin W. King
Summary: Currently, there is no available small-caliber vascular graft for coronary or carotid artery repair or bypass. In this study, a textile-reinforced hydrogel vascular graft is developed. The textile fibers form a flexible and robust conduit which serves as the mechanical support, and it is embedded in a hydrogel matrix to promote faster reendothelialization. The composite graft exceeds the mechanical requirements and enhances endothelial cell adhesion and proliferation. Overall, the textile-reinforced hydrogel shows promise as a scaffold material for tissue engineered vascular grafts.
Article
Plant Sciences
Jia-Wen Shi, Zhuang-Zhuang Li, Jia-Shuo Wu, Wei-Yi Jin, Xiao-Yan Chang, Hong Sun, Li Dong, Zhi-Ping Jiang, Yue Shi
Summary: The study identified specific herbal components in Banxia Xiexin Decoction (BXD) that were associated with reduced intestinal SN-38 levels in mice treated with CPT-11, including chrysin, berberine, and baicalin. These compounds were proposed as the primary bioactive components of BXD, offering protection against chemotherapy-induced diarrhea. This spectrum-effect analysis provides valuable insights into the pharmacological activity of traditional Chinese medicine preparations.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Behavioral Sciences
Wiebke Herrmann, Jan Wacker
Summary: The study suggests a relationship between agentic extraversion and executive functions due to shared influences of individual differences in the dopamine system, particularly for tasks like 3-back and switching. However, it was found that some of this association is partly due to shared dopamine-based processes among tasks, indicating that variance components and measurement difficulties of EF tasks should be considered when investigating personality-related individual differences in EFs.
COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE
(2021)
Article
Engineering, Biomedical
Aditya Kumar, Starry He, Prashant Mali
Summary: Researchers established an experimental framework for systematic identification of maturation enhancing factors in human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs). Through transcriptome RNAseq analyses, they identified 22 transcription factors (TFs) whose expression progressively increased in 3D culture systems and adult mature cell types. Overexpression of five of these TFs (KLF15, ZBTB20, ESRRA, HOPX, and CAMTA2) individually improved calcium handling, metabolic function, and hypertrophy. Combinatorial overexpression of KLF15, ESRRA, and HOPX simultaneously improved all three maturation parameters.
APL BIOENGINEERING
(2023)
Article
Biochemistry & Molecular Biology
Lijie Shi, Silvia E. Racedo, Alexander Diacou, Taeju Park, Bin Zhou, Bernice E. Morrow
Summary: CRK and CRKL genes play crucial roles in NCCs, and their loss can lead to cardiac malformation and abnormal aortic arch development. These defects may be attributed to altered NCCs localization and function, as well as reduced differentiation of vascular smooth muscle cells.
HUMAN MOLECULAR GENETICS
(2022)
Article
Multidisciplinary Sciences
Qin Gong, Kim Robinson, Chenrui Xu, Phuong Thao Huynh, Kelvin Han Chung Chong, Eddie Yong Jun Tan, Jiawen Zhang, Zhao Zhi Boo, Daniel Eng Thiam Teo, Kenneth Lay, Yaming Zhang, John Soon Yew Lim, Wah Ing Goh, Graham Wright, Franklin L. Zhong, Bruno Reversade, Bin Wu
Summary: NLRP1 and CARD8 are two recently characterized sensor proteins for the human inflammasome complex. The cryo-EM CARD filament structures of the NLRP1 and CARD8 activating domains reveal how NLRP1 and CARD8 discriminate between ASC and pro-caspase-1. The authors propose a two-step model for NLRP1 activation.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Geetika Sahni, Shu-Yung Chang, Jeremy Teo Choon Meng, Jerome Zu Yao Tan, Jean Jacques Clement Fatien, Carine Bonnard, Kagistia Hana Utami, Puck Wee Chan, Thong Teck Tan, Umut Altunoglu, Hulya Kayserili, Mahmoud Pouladi, Bruno Reversade, Yi-Chin Toh
Summary: Research has successfully directed the formation of neural embryonic tissues from human pluripotent stem cells, replicating cellular processes relevant to early neurodevelopment. Spatial-temporal patterning of mesoendoderm guides the development of primitive ectoderm, facilitating tissue folding of the prospective neuroepithelium. The model allows for detection of structural dysmorphia in neuroepithelium tissues and differentiation between neural tube defect-inducing drugs.
Article
Cardiac & Cardiovascular Systems
David Coquerel, Eugenie Delile, Lauralyne Dumont, Frederic Chagnon, Alexandre Murza, Xavier Sainsily, Dany Salvail, Philippe Sarret, Eric Marsault, Mannix Auger-Messier, Olivier Lesur
Summary: By utilizing G alpha i-biased APJ agonists, it is possible to regulate cardiac function and potentially offer a protective impact in the treatment of cardiovascular diseases.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2021)
Article
Chemistry, Medicinal
Magali Chartier, Michael Desgagne, Marc Sousbie, Jerome Cote, Jean-Michel Longpre, Eric Marsault, Philippe Sarret
Summary: The study presents the synthesis and functional in vivo characterization of the first NTS2-selective macrocyclic NT analog, demonstrating potent analgesic effects in rodent pain models without undesired effects associated with NTS1 activation. This highlights the strong therapeutic potential of NTS2-selective analogs for acute and chronic pain management.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Behavioral Sciences
Melanie Vivancos, Roberto Fanelli, Elie Besserer-Offroy, Sabrina Beaulieu, Magali Chartier, Martin Resua-Rojas, Christine E. Mona, Santo Previti, Emmanuelle Remond, Jean-Michel Longpre, Florine Cavelier, Philippe Sarret
Summary: The chemically-modified NT(8-13) analog JMV5296 showed a prolonged plasma half-life, peptide selectivity toward NTS2, and induced a strong antinociceptive effect in acute, tonic, and chronic pain models without inducing hypothermia, suggesting it as a promising avenue for new stable NT agonists development and improvement of pain management.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Article
Multidisciplinary Sciences
Nairie Michaelian, Anastasiia Sadybekov, Elie Besserer-Offroy, Gye Won Han, Harini Krishnamurthy, Beata A. Zamlynny, Xavier Fradera, Phieng Siliphaivanh, Jeremy Presland, Kerrie B. Spencer, Stephen M. Soisson, Petr Popov, Philippe Sarret, Vsevolod Katritch, Vadim Cherezov
Summary: The leukotriene B4 receptor 1 (BLT1) plays a role in various human diseases and the crystal structure study reveals molecular determinants of ligand binding and selectivity toward different receptor subtypes, providing insights for future structure-based drug design.
NATURE COMMUNICATIONS
(2021)
Article
Health Care Sciences & Services
Lise Dassieu, Emilie Paul-Savoie, Elise Develay, Ana Cecilia Villela Guilhon, Anais Lacasse, Line Guenette, Kadija Perreault, Helene Beaudry, Laurent Dupuis
Summary: This study aimed to understand experiences of people living with chronic pain and community pharmacists regarding the management of analgesic adverse effects. Patients and pharmacists had varying definitions of adverse effects, leading to dilemmas and discrepancies in decision-making. Pharmacists faced barriers in supporting patients due to organizational and financial constraints.
HEALTH EXPECTATIONS
(2022)
Article
Chemistry, Medicinal
Kien Tran, Xavier Sainsily, Jerome Cote, David Coquerel, Pierre Couvineau, Sabrina Saibi, Lounes Haroune, Elie Besserer-Offroy, Joel Flynn-Robitaille, Martin Resua Rojas, Alexandre Murza, Jean-Michel Longpre, Mannix Auger-Messier, Olivier Lesur, Michel Bouvier, Eric Marsault, Pierre-Luc Boudreault, Philippe Sarret
Summary: We have developed novel macrocyclic compounds of Ape13, analogues 39 and 40, which have reduced molecular weight and specific pharmacological profiles.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Cecile Petigny, Audrey-Ann Dumont, Hugo Giguere, Audrey Collette, Brian J. Holleran, Mircea Iftinca, Christophe Altier, Elie Besserer-Offroy, Mannix Auger-Messier, Richard Leduc
Summary: In this study, BRET biosensors were developed to study the conformational changes of TRPC channels following receptor activation. The biosensors were tested in both cell lines and physiological conditions and showed successful detection of conformational changes. The results suggest that G alpha(q)-coupled receptor activation induces conformational changes in the TRPC7 BRET biosensor.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Shifeng Xue, Thanh Thao Nguyen Ly, Raunak S. Vijayakar, Jingyi Chen, Joel Ng, Ajay S. Mathuru, Frederique Magdinier, Bruno Reversade
Summary: This study reveals that Smchd1 regulates Hox gene expression at an epigenetic level in mammals, and its loss causes precocious and ectopic Hox transcription. The loss of maternal Smchd1 also leads to Hox epimutations and affects the vertebral patterning in offspring. Furthermore, the regulation is mediated by the direct interacting partner Lrif1.
NATURE COMMUNICATIONS
(2022)
Article
Developmental Biology
Hyuk Nam Kwon, Kristen Kurtzeborn, Vladislav Iaroshenko, Xing Jin, Abigail Loh, Nathalie Escande-Beillard, Bruno Reversade, Sunghyouk Park, Satu Kuure
Summary: Nephron endowment plays a crucial role in adult renal health, and defects in the molecular regulation of nephron progenitors can lead to reduced nephron mass. This study characterized the metabolic consequences of MAPK/ERK deficiency and identified pyruvate and proline as important factors in nephron progenitor maintenance.
Article
Dermatology
Mingfeng Li, Kenneth Lay, Andreas Zimmer, Kristin Technau-Hafsi, Jasmine Wong, Antonia Reimer-Taschenbrecker, Jan Rohr, Ebtesam Abdalla, Judith Fischer, Bruno Reversade, Cristina Has
Summary: A previously unreported NLRP1 gene variant was identified, leading to different clinical presentations in two sisters. The variant triggered the activation of inflammation and resulted in different severity of skin manifestations.
BRITISH JOURNAL OF DERMATOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Santo Previti, Michael Desgagne, Dirk Tourwe, Florine Cavelier, Philippe Sarret, Steven Ballet
Summary: Chronic pain is a global health issue and opioid drugs are commonly used for pain management. However, they come with adverse effects. Neurotensin (NT) ligands have shown promising potential for pain management, without the adverse effects of opioids.
JOURNAL OF PEPTIDE SCIENCE
(2023)
Article
Biology
Eva Hasel de Carvalho, Shivani S. Dharmadhikari, Kateryna Shkarina, Jingwei Rachel Xiong, Bruno Reversade, Petr Broz, Maria Leptin
Summary: The researchers constructed a light-responsive form of the inflammasome adaptor protein, allowing tight control of inflammasome formation within cells. By introducing this construct into zebrafish, they were able to induce inflammasome formation in individual skin cells. They found that the resulting cell death from inflammasome formation varied morphologically in different cell types.