Article
Multidisciplinary Sciences
Caroline Gubser Keller, Youngah Shin, Alex Mas Monteys, Nicole Renaud, Martin Beibel, Natalia Teider, Thomas Peters, Thomas Faller, Sophie St-Cyr, Judith Knehr, Guglielmo Roma, Alejandro Reyes, Marc Hild, Dmitriy Lukashev, Diethilde Theil, Natalie Dales, Jang-Ho Cha, Beth Borowsky, Ricardo Dolmetsch, Beverly L. Davidson, Rajeev Sivasankaran
Summary: Huntington's Disease is a neurodegenerative disorder caused by CAG repeat expansions in the HTT gene. The orally available and brain penetrant small molecule branaplam lowers HTT transcript by promoting inclusion of a poison exon or pseudoexon.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Fredrik R. Zetterberg, Alison MacKinnon, Thomas Brimert, Lise Gravelle, Richard E. Johnsson, Barbro Kahl-Knutson, Hakon Leffler, Ulf J. Nilsson, Anders Pedersen, Kristoffer Peterson, James A. Roper, Hans Schambye, Robert J. Slack, Susan Tantawi
Summary: This study presents a series of selective galectin-3 inhibitors with high affinity and oral bioavailability. These compounds show antifibrotic activity in fibrosis-related diseases and one of them has been selected as a clinical candidate for further research.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Fredrik R. Zetterberg, Alison MacKinnon, Thomas Brimert, Lise Gravelle, Richard E. Johnsson, Barbro Kahl-Knutson, Hakon Leffler, Ulf J. Nilsson, Anders Pedersen, Kristoffer Peterson, James A. Roper, Hans Schambye, Robert J. Slack, Susan Tantawi
Summary: Galectin-3 is a crucial carbohydrate-binding protein involved in the regulation of various diseases. The discovery of GB0139, a high-affinity drug for idiopathic pulmonary fibrosis, has opened up new possibilities for treatment. By optimizing physical and chemical parameters, a series of highly selective galectin-3 inhibitors with both high affinity and oral bioavailability have been developed. These compounds have demonstrated anti-fibrotic activity in liver and lung fibrosis mouse models and show promising pharmacokinetic and safety profiles. GB1211 has been selected as a clinical candidate for liver cirrhosis and cancer, and phase IIa clinical trials are currently underway.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Microbiology
Bao-Xue Quan, Huiping Shuai, An-Jie Xia, Yuxin Hou, Rui Zeng, Xin-Lei Liu, Gui-Feng Lin, Jing-Xin Qiao, Wen-Pei Li, Fa-Lu Wang, Kai Wang, Ren-Jie Zhou, Terrence Tsz-Tai Yuen, Ming-Xin Chen, Chaemin Yoon, Ming Wu, Shi-Yu Zhang, Chong Huang, Yi-Fei Wang, Wei Yang, Chenyu Tian, Wei-Min Li, Yu-Quan Wei, Kwok-Yung Yuen, Jasper Fuk-Woo Chan, Jian Lei, Hin Chu, Shengyong Yang
Summary: This study reports a promising lead compound, Y180, for oral drug development against SARS-CoV-2. Y180, an inhibitor of the main protease (Mpro), demonstrated therapeutic efficacy against wild-type SARS-CoV-2 and its variants, including the Omicron variant, after oral administration. It improved survival in a humanized mouse model.
NATURE MICROBIOLOGY
(2022)
Article
Microbiology
Courtney L. Finch, Julie Dyall, Shuang Xu, Elizabeth A. Nelson, Elena Postnikova, Janie Y. Liang, Huanying Zhou, Lisa Evans DeWald, Craig J. Thomas, Amy Wang, Xin Xu, Emma Hughes, Patrick J. Morris, Jon C. Mirsalis, Linh H. Nguyen, Maria P. Arolfo, Bryan Koci, Michael R. Holbrook, Lisa E. Hensley, Peter B. Jahrling, Connie Schmaljohn, Lisa M. Johansen, Gene G. Olinger, Joshua T. Schiffer, Judith M. White
Summary: The text discusses recent advancements in managing Ebola virus disease (EVD) with the approval of an Ebola vaccine and two monoclonal antibody therapies. It introduces the idea of a combined therapy for multiple filoviruses and presents initial experiments on two drug combinations in cell cultures and mouse models. Pharmacokinetic studies show promising results with oral delivery of drugs, indicating potential for further synergistic testing in EVD mouse models and potential increased efficacy in humans based on mathematical modeling.
Article
Multidisciplinary Sciences
Magdalena Zimon, Yunfeng Huang, Anthi Trasta, Aliaksandr Halavatyi, Jimmy Z. Liu, Chia-Yen Chen, Peter Blattmann, Bernd Klaus, Christopher D. Whelan, David Sexton, Sally John, Wolfgang Huber, Ellen A. Tsai, Rainer Pepperkok, Heiko Runz
Summary: Studying the contribution of pairs of genes to complex traits has been challenging. Here, the authors combine exome and genotype data with RNAi to screen for genetic interactions between 30 genes identified in lipid GWAS to hint at pairs whose joint modulation may improve lipid-lowering therapies.
NATURE COMMUNICATIONS
(2021)
Article
Nanoscience & Nanotechnology
Sedat Unal, Osman Dogan, Yesim Aktas
Summary: This study aims to develop an oral nanoparticle drug delivery system for the treatment of intestinal tumors. By using poly(lactic-co-glycolic acid) (PLGA) as the nanoparticle material and modified with chitosan (CS) for improved mucoadhesive properties, a nanoparticle formulation that can accumulate in mucus and protect the drug has been designed. In vitro experiments showed that the formulation has favorable nanoparticle size and sustained release characteristics, as well as significant cytotoxicity and permeability, offering a promising and innovative approach for the treatment of intestinal tumors.
BEILSTEIN JOURNAL OF NANOTECHNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Cynthia L. Bristow, Ronald Winston
Summary: This study investigates the role of plasma α1-proteinase inhibitor (α1PI) in lipoprotein regulation and the development of orally available small molecules as substitutes for α1PI. It demonstrates that certain beta-lactam compounds have the potential to act as α1PI surrogates by binding to specific proteins and reducing LDL levels.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Kazunori Kadota, Hirohito Terada, Ayaka Fujimoto, Satoshi Nogami, Hiromasa Uchiyama, Yuichi Tozuka
Summary: Orally disintegrating tablets (ODTs) improve patient adherence by easily disintegrating in the presence of saliva, but the bitter taste of active pharmaceutical ingredients can reduce compliance. This study aimed to formulate ODTs with high-dose memantine hydrochloride while masking the bitter taste. ODTs coated with enteric polymers showed the fastest disintegration time and reduced bitterness, demonstrating a potential for improved patient experience.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Allergy
Edward J. Duckworth, Nivetha Murugesan, Lily Li, Louise J. Rushbrooke, Daniel K. Lee, Gian Marco De Donatis, Andreas Maetzel, Christopher M. Yea, Sally L. Hampton, Edward P. Feener
Summary: This report describes the pharmacological and pharmacodynamic properties of the novel oral small-molecule PKa inhibitor KVD900 for the potential on-demand treatment of HAE. The results show that orally administered KVD900 rapidly inhibits PKa activity, kallikrein kinin system activation, and HK cleavage in plasma, providing an opportunity to halt the generation of bradykinin and reverse HAE attacks.
CLINICAL AND EXPERIMENTAL ALLERGY
(2022)
Article
Pharmacology & Pharmacy
Adelaide Jewell, Hannah Williams, Caroline L. Hoad, Paul R. Gellert, Marianne B. Ashford, James Butler, Snow Stolnik, David Scurr, Michael J. Stocks, Luca Marciani, Penny A. Gowland, Pavel Gershkovich
Summary: This study evaluated the feasibility of MRI for imaging lipid uptake into the intestinal lymphatics, shedding light on targeted lymph nodes. The method described has potential for repeated lymph node measurements and tracking lipid uptake. Future studies should focus on optimizing the methodology in a larger cohort.
Article
Biochemistry & Molecular Biology
Amrinder Singh, Shubham Thakur, Harmanpreet Singh, Harjeet Singh, Sandeep Kaur, Satwinderjeet Kaur, Rajesh Dudi, Dilip Manikrao Mondhe, Subheet Kumar Jain
Summary: The study successfully developed a novel nanovesicular formulation of DTX based on Vitamin E TPGS, which exhibited nanometric size, spherical vesicular shape, high drug encapsulation efficiency, sustained-release profile, and high dilution integrity with normal saline. In vitro cytotoxicity assay showed significantly increased IC50 value compared to the commercial formulation, and in vivo anticancer activity demonstrated significant tumor growth inhibition. This novel formulation could potentially offer improved therapeutic efficacy, reduced toxicity, and sustained drug release behavior.
JOURNAL OF LIPOSOME RESEARCH
(2021)
Article
Immunology
Brady Trevisan, Martin Rodriguez, Hailey Medder, Shannon Lankford, Rebecca Combs, John Owen, Anthony Atala, Christopher D. Porada, Graca Almeida-Porada
Summary: This study demonstrates the potential of using autologous bone marrow-derived mesenchymal stromal cells as cellular delivery vehicles for long-term expression of FVIII in the treatment of hemophilia A.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Wael Alturaiki
Summary: This study investigated the plasma protein concentrations of total IgE and TSLP cytokines in patients with chronic stable asthma. The results showed higher levels of total IgE and TSLP in asthma patients compared to normal controls. Additionally, the expression of TSLP-r on B cells was also significantly higher in asthma patients. Measuring plasma levels of TSLP in patients with stable asthma may be used to assess asthma symptoms and evaluate the efficacy of corticosteroid therapy.
JOURNAL OF KING SAUD UNIVERSITY SCIENCE
(2022)
Article
Oncology
Rekha Priyadarshini, Gerard Marshall Raj, Rajan Sundaram, Smita Kayal, Ananthakrishnan Ramesh, Deepak Gopal Shewade
Summary: This study demonstrated a significant association between SNP rs1128503 (C1236T) in the ABCB1 gene and plasma levels of docetaxel, while SNP rs1045642 (C3435T) showed no association. Patients with higher plasma levels of docetaxel had better tumor response.
Review
Biochemistry & Molecular Biology
Haitao Wang, Jiangping Xu, Philip Lazarovici, Wenhua Zheng
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2017)
Article
Biochemistry & Molecular Biology
Galit Gincberg, Esther Shohami, Philip Lazarovici, Uriel Elchalal
JOURNAL OF MOLECULAR NEUROSCIENCE
(2018)
Article
Cell & Tissue Engineering
Galit Gincberg, Esther Shohami, Victoria Trembovler, Alexander G. Alexandrovich, Philip Lazarovici, Uriel Elchalal
Article
Biochemistry & Molecular Biology
Galia Tiram, Shiran Ferber, Paula Ofek, Anat Eldar-Boock, Dikla Ben-Shushan, Eilam Yeini, Adva Krivitsky, Roni Blatt, Nava Almog, Jack Henkin, Orit Amsalem, Eylon Yavin, Gadi Cohen, Philip Lazarovici, Joo Sang Lee, Eytan Ruppin, Michael Milyavsky, Rachel Grossman, Zvi Ram, Marcelo Calderon, Rainer Haag, Ronit Satchi-Fainaro
Review
Neurosciences
Haitao Wang, Jiangping Xu, Philip Lazarovici, Remi Quirion, Wenhua Zheng
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2018)
Review
Food Science & Technology
Philip Lazarovici, Cezary Marcinkiewicz, Peter I. Lelkes
Review
Cell Biology
Yizhou Jiang, Fengxia Yan, Zhongping Feng, Philip Lazarovici, Wenhua Zheng
Article
Biochemistry & Molecular Biology
Chaim Gilon, Agata Gitlin-Domagalska, Adi Lahiani, Shiran Yehoshua-Alshanski, Adi Shumacher-Klinger, Dan Gilon, Mahmoud Taha, Israel Sekler, Amnon Hoffman, Philip Lazarovici
Review
Biochemistry & Molecular Biology
Limor Rubin, Collin T. Stabler, Adi Schumacher-Klinger, Cezary Marcinkiewicz, Peter Lelkes, Philip Lazarovici
Summary: This review explores the role of neurotrophins in neurogenesis, vasculogenesis, and embryonic development of the respiratory system, as well as their implications for respiratory diseases.
CYTOKINE & GROWTH FACTOR REVIEWS
(2021)
Article
Cell Biology
Lijun Ge, Shuyuan Liu, Limor Rubin, Philip Lazarovici, Wenhua Zheng
Summary: Insulin-like growth factor-1 (IGF-1) and its binding proteins and receptors are expressed in the central nervous system (CNS), playing a neurotrophic role in normal growth and development. Recent research suggests that IGF-1 may also have neuroprotective effects in neurological disorders such as stroke, brain trauma, Alzheimer's disease, and epilepsy, by modulating glutamate-mediated excitotoxic signaling pathways. Animal studies and clinical trials have demonstrated the potential therapeutic value of IGF-1 in CNS diseases. This review focuses on the relationship between IGF-1-induced neuroprotection and glutamate-induced excitatory neurotoxicity, providing a basis for the clinical application of IGF-I as a neuroprotective therapy for neurological diseases associated with glutamate excitotoxicity.
Article
Materials Science, Multidisciplinary
Majdi Saleem Naamneh, Philip Lazarovici, Jehoshua Katzhendler
Summary: This study investigated the activity of different organocatalysts and initiators in the ring-opening polymerization of OCAs derived from phenylalanine. It found that dimethylaminoethyl amine and dimethylaminopropyl amine were highly active catalysts for controlled polymerization, while 4-(Hydroxymethyl)-1H-imidazole was the most effective catalyst for uncontrolled polymerization in the presence of 4-DMAP. The study highlights the potential application of Phe-OCA polymers in biomedical materials and provides important implications for the synthesis of polymeric polyesters in translational medicine.
ACS APPLIED POLYMER MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
Michal Klazas, Majdi Saleem Naamneh, Wenhua Zheng, Philip Lazarovici
Summary: The study aimed to investigate the protective effect of gabapentin on Taxol-induced peripheral neuropathy and its impact on intra-epidermal nerve fibers density.
Article
Biochemistry & Molecular Biology
David Lankri, Dikla Haham, Adi Lahiani, Philip Lazarovici, Dmitry Tsvelikhovsky
ACS CHEMICAL NEUROSCIENCE
(2018)
Review
Neurosciences
Adi Lahiani, Annette Brand-Yavin, Ephraim Yavin, Philip Lazarovici
Article
Biochemistry & Molecular Biology
Matan Geron, Rakesh Kumar, Henry Matzner, Adi Lahiani, Galit Gincberg, Gadi Cohen, Philip Lazarovici, Avi Priel
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2017)