Article
Multidisciplinary Sciences
Zhong Li, Anil Mathew Tharappel, Jimin Xu, Yuekun Lang, Cathleen M. Green, Jing Zhang, Qishan Lin, Sudha Chaturvedi, Jia Zhou, Marlene Belfort, Hongmin Li
Summary: A small-molecule library was screened to find potent inhibitors of the Cne Prp8 intein, leading to the identification of compound 6G-318S with potential antifungal properties. These inhibitors showed specific action against Cryptococcus species and demonstrated synergistic effects with certain antimycotics. Their binding to the target Prp8 intein was covalent and mutation of the active-site residue reduced binding, highlighting their potential as a new class of antifungal drugs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Medicinal
Thomas A. Chappie, Mario Abdelmessih, Claude W. Ambroise, Markus Boehm, Mi Cai, Michael Green, Edward Guilmette, Claire M. Steppan, Lucy M. Stevens, Liuqing Wei, Simon Xi, Samuel A. Hasson
Summary: CD33/Siglec 3 is a receptor that regulates microglia activity and genetic variants of it can protect against late-onset Alzheimer's disease. Compounds that affect CD33 splicing provide a starting point for exploring small molecules that alter neuroimmune function in neurodegenerative diseases.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Review
Chemistry, Medicinal
Lijuan Xu, Chunlin Zhuang
Summary: This article presents an in-depth study of the ligand-kinase interactions in the crucial cleft areas of RIPK1 and RIPK3. The structural similarity and differential segments of ligands are systematically evaluated, providing new insights into the adaption of conserved and selective kinase domains to chemical diversity. The analysis can guide the discovery and optimization of inhibitors for RIPK1 and RIPK3.
MEDICINAL RESEARCH REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Laura Depta, Thomas Whitmarsh-Everiss, Luca Laraia
Summary: This review focuses on the importance of intracellular sterol transport proteins (STPs) in maintaining cellular lipid homeostasis. It highlights their substrate specificities and intracellular localisation, as well as their functions in health and disease. The review also discusses recent advances in the identification of small molecule modulators of STPs and their potential therapeutic applications.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Riccardo Rozza, Pavel Janos, Angelo Spinello, Alessandra Magistrato
Summary: RNA splicing plays a pivotal role in gene expression and deregulated splicing is linked to various diseases. The discovery of small-molecule splicing-modulators offers therapeutic opportunities. Structural data and all-atom simulations contribute to understanding splicing regulation and can aid in drug discovery efforts.
EXPERT OPINION ON DRUG DISCOVERY
(2022)
Article
Chemistry, Multidisciplinary
Qianglong Lv, Cunbin An, Tao Zhang, Jianqi Zhang, Shaoqing Zhang, Pengxin Zhou, Chang He, Jianhui Hou
Summary: Three small-molecule donors were designed and synthesized with different terminal alkyl chains, affecting their crystallinity and phase-separation morphology in blend films. Among them, BPF3T-C6 showed the best performance with a power conversion efficiency of 15.1%.
SCIENCE CHINA-CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Min-Min Tang, Kuppusamy Kanagaraj, Julius Rebek, Yang Yu
Summary: Groups on the upper rim of cavitands play a significant role in the recognition of small molecules. This study synthesized and characterized water-soluble deep cavitands with different upper rim groups and investigated their interactions with small-molecule guests.
CHEMISTRY-AN ASIAN JOURNAL
(2022)
Article
Cell Biology
Esra Albayrak, Merve Uslu, Sezer Akgol, Emre Can Tuysuz, Fatih Kocabas
Summary: Research suggests that modulation of ubiquitination and neddylation can enhance the function of hematopoietic stem cells (HSCs) by improving their quiescence and self-renewal capacity. Inhibition of ubiquitination and neddylation can increase murine and human stem and progenitor cell compartments, as well as enhance in vitro self-renewal potential. Additionally, inhibition of these processes may trigger bone marrow HSPCs mobilization while decreasing the proliferation of other bone marrow cells. These findings highlight the importance of SKP2, ubiquitination and neddylation in HSC maintenance and expansion.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Chemistry, Applied
Yuwei Duan, Xiaopeng Xu, Liyang Yu, Ying Li, Ruipeng Li, Qiang Peng
Summary: The molecular planarity of small molecule donor affects molecular packing, blend morphology, and photovoltaic properties of organic solar cells. Chemical modifications such as sulfuration and introduction of alkoxy groups were used to enhance planarity and induce various non-covalent interactions. End groups, like rhodanine and cyanoacetate, influenced molecular packing and blend morphology. The study provides insights on the impact of donor and acceptor packing behavior on photovoltaic properties through molecular design.
Article
Chemistry, Medicinal
Hasane Ratni, Renata S. Scalco, Alexander H. Stephan
Summary: Targeting mRNA with small molecules, once considered a challenging scientific task, has now become a viable technology for developing new drugs with high therapeutic relevance. This exciting platform has been established through the discovery of small molecule splicing modifiers and the development of drugs like risdiplam for treating diseases such as SMA.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Multidisciplinary Sciences
Tobias Raisch, Andreas Brockmann, Ulrich Ebbinghaus-Kintscher, Jorg Freigang, Oliver Gutbrod, Jan Kubicek, Barbara Maertens, Oliver Hofnagel, Stefan Raunser
Summary: Slowpoke (Slo) potassium channels, which have high conductance and are activated by positive transmembrane potential and high intracellular Ca2+ concentrations, are targets for insecticides and antiparasitic drugs. The study presents cryo-EM structures of Drosophila Slo in Ca2+-bound and Ca2+-free forms, as well as in complex with fungal neurotoxin verruculogen and anthelmintic drug emodepside, revealing potential insect-specific binding pockets and mechanisms of action on Slo channel activity.
NATURE COMMUNICATIONS
(2021)
Article
Nanoscience & Nanotechnology
Qinrui Ye, Jinfeng Ge, Dandan Li, Zhenyu Chen, Jingyu Shi, Xiaoli Zhang, Erjun Zhou, Daobin Yang, Ziyi Ge
Summary: This work demonstrates the importance of fine-tuning the phase-separated morphology in achieving efficient ASM-OSCs. By designing and synthesizing a pair of isomers, the substitution site of fluorine atoms was adjusted to improve the power conversion efficiency of ASM-OSCs.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Nanoscience & Nanotechnology
Qinrui Ye, Jinfeng Ge, Dandan Li, Zhenyu Chen, Jingyu Shi, Xiaoli Zhang, Erjun Zhou, Daobin Yang, Ziyi Ge
Summary: Fine-tuning the phase-separated morphology of all-small-molecule organic solar cells (ASM-OSCs) is crucial for achieving high efficiency. In this study, a pair of isomers, BDT-UF and BDT-DF, were designed and synthesized. The positioning of the fluorine atom was found to affect the molecular planarity and crystallinity of the blend films, leading to improved power conversion efficiency (PCE) of the devices.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Review
Oncology
Zhihui Dou, Dapeng Zhao, Xiaohua Chen, Caipeng Xu, Xiaodong Jin, Xuetian Zhang, Yupei Wang, Xiaodong Xie, Qiang Li, Cuixia Di, Hong Zhang
Summary: The study of Bcl-x pre-mRNA splicing reveals its crucial role in cell death regulation and its dysregulation is associated with various human diseases, particularly cancers. Understanding the mechanism and regulation of Bcl-x splicing has provided insights for drug development to enhance cancer cell sensitivity to death, highlighting the significance of aberrant splicing isoforms of Bcl-x as targets for cancer therapy.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Review
Pharmacology & Pharmacy
Scott J. Barraza, Anuradha Bhattacharyya, Christopher R. Trotta, Matthew G. Woll
Summary: The concept of using small molecules to modulate pre-mRNA splicing was validated with FDA approval of risdiplam in 2020. Efforts have continued towards the discovery of new splicing-modulating drugs, taking advantage of new insights into RNA-processing pathways and regulatory networks. This review provides a compilation and summary of small molecules discovered and developed since 2020 to alter pre-mRNA splicing, organized by classes of biological targets.
DRUG DISCOVERY TODAY
(2023)
Article
Cell Biology
Pamposh Raina, S. K. Singh, Anil K. Goswami, Manoj Kumar Kashyap, Madhu Khullar, S. K. Sharma, Kailash Chander Barwal
Summary: MN/CA9, a cell surface glycoprotein and tumor-associated antigen, plays a crucial role in cell proliferation and oncogenesis. The study showed a correlation between MN/CA9 gene expression in blood and tumor tissue samples of RCC patients, suggesting its potential importance in the diagnosis and management of RCC.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2022)
Editorial Material
Cell & Tissue Engineering
James J. Yoo
CURRENT STEM CELL RESEARCH & THERAPY
(2023)
Article
Cell Biology
Deepak Kumar, Manoj K. Kashyap, Zhe Yu, Ide Spaanderman, Reymundo Villa, Thomas J. Kipps, James J. La Clair, Michael D. Burkart, Januario E. Castro
Summary: Alterations in RNA splicing are associated with malignancies. This study found that the RNA splicing modulators FD-895 and pladienolide B can induce higher apoptosis levels and inhibit solid tumor growth by modulating the Wnt signaling pathway and mRNA splicing.
Letter
Oncology
Jacqui-Lyn Saw, M. Hasib Sidiqi, Michael Ruff, Sara Hocker, Hassan Alkhateeb, Stephen M. Ansell, N. Nora Bennani, David Dingli, Suzanne R. Hayman, Patrick B. Johnston, Prashant Kapoor, Saad J. Kenderian, Taxiarchis V. Kourelis, Shaji K. Kumar, Jonas Paludo, Mithun V. Shah, Mustaqeem A. Siddiqui, Rahma Warsame, Allison Rosenthal, Marie Grill, Januario E. Castro, Jason Siegel, Zaid H. Abdel Rahman, Mohamed A. Kharfan-Dabaja, Elson So, Yi Lin
BLOOD CANCER JOURNAL
(2022)
Letter
Hematology
Evandro D. Bezerra, Madiha Iqbal, Javier Munoz, Arushi Khurana, Yucai Wang, Matthew J. Maurer, Radhika Bansal, Matthew A. Hathcock, Nora Bennani, Hemant S. Murthy, Allison C. Rosenthal, Jonas Paludo, Jose C. Villasboas, Patrick B. Johnston, Thomas M. Habermann, Stephen M. Ansell, Januario E. Castro, Thomas E. Witzig, Mohamed A. Kharfan-Dabaja, Grzegorz S. Nowakowski, Yi Lin
Review
Oncology
Ginna Granroth, Allison Rosenthal, Maggie McCallen, Christopher Coughlin, Hollie Benson, Jeanne Palmer, Januario E. Castro, Javier Munoz
Summary: This paper aims to describe the comprehensive supportive care for patients with relapsed or refractory lymphoma undergoing cellular therapy, focusing on the perspective of advanced practice providers (APPs). Recent findings indicate that CAR-T cell therapy is increasingly used for treating relapsed or refractory B-cell hematologic malignancies. APPs play a pivotal role in supporting these patients throughout their treatment.
CURRENT ONCOLOGY REPORTS
(2022)
Editorial Material
Oncology
Xiujing He, Manoj Kumar Kashyap, Zhizhuang Joe Zhao, Jian Yu, Hubing Shi
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Julia E. Wiedmeier-Nutor, Madiha Iqbal, Allison C. Rosenthal, Evandro D. Bezerra, Juan Esteban Garcia-Robledo, Radhika Bansal, Patrick B. Johnston, Matthew Hathcock, Jeremy T. Larsen, P. Leif Bergsagel, Yucai Wang, Craig B. Reeder, Jose F. Leis, Rafael Fonseca, Jeanne M. Palmer, Brianna J. Gysbers, Raphael Mwangi, Rahma M. Warsame, Taxiarchis Kourelis, Suzanne R. Hayman, David Dingli, Prashant Kapoor, Shaji K. Kumar, Urshila Durani, Jose C. Villasboas, Jonas Paludo, N. Nora Bennani, Grzegorz Nowakowski, Stephen M. Ansell, Januario E. Castro, Mohamed A. Kharfan-Dabaja, Yi Lin, Paschali Veridis, Hemant S. Murthy, Javier Munoz
Summary: This study evaluated the levels of SARS-CoV-2 spike-binding IgG antibodies in non-Hodgkin lymphoma and multiple myeloma CAR T therapy recipients after COVID-19 vaccination. It found that only a minority of these patients were able to mount a clinically relevant antibody response (> 250 IU/mL).
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Review
Genetics & Heredity
Mohanraj Gopikrishnan, R. Hephzibah Cathryn, R. Gnanasambandan, Hossam M. Ashour, Gianfranco Pintus, Mohamed Hammad, Manoj Kumar Kashyap, C. George Priya Doss, Hatem Zayed
Summary: Circular RNAs (circRNAs) function as regulatory elements in orchestrating gene expression and protein functions, and have been implicated in various biological processes, including cancer. This review summarizes the roles of circRNAs in breast cancer, particularly in its initiation, progression, metastasis, and drug resistance. CircRNAs can indirectly influence gene expression by acting as miRNA sponges, disrupting miRNA regulation of target genes. They can also interact with proteins and modulate their functions, including signaling pathways involved in cancer development. Furthermore, circRNAs can encode peptides that play a role in breast cancer pathophysiology, making them potential diagnostic biomarkers and therapeutic targets. Challenges and prospects associated with the clinical use of circRNAs in breast cancer are also discussed.
FUNCTIONAL & INTEGRATIVE GENOMICS
(2023)
Review
Cell Biology
Ambikesh Soni, Manohar Prasad Bhandari, Gagan Kant Tripathi, Priyavand Bundela, Pradeep Kumar Khiriya, Purnima Swarup Khare, Manoj Kumar Kashyap, Abhijit Dey, Balachandar Vellingiri, Suresh Sundaramurthy, Arisutha Suresh, Jose M. de la Lastra
Summary: In recent years, the nanobiotechnology approach has been considered by drug manufacturers and researchers to improve the drug delivery system for tumour and cancer diseases. This article reviews current strategies to improve tumour and cancer drug delivery, focusing on biocompatibility, biodistribution, and active targeting. Nanoparticle-based drug delivery provides target-specific delivery and controlled release, offering a better therapeutic window for treatment options by eradicating diseased cells while sparing normal cells. Nanoparticle-based therapy also overcomes the challenges of treating brain tumors by breaching the blood-brain barriers, improving drug delivery to the target.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2023)
Editorial Material
Genetics & Heredity
Zahra Sadat Hashemi, Mahlegha Ghavami, Manoj Kumar Kashyap
FRONTIERS IN GENETICS
(2023)
Review
Endocrinology & Metabolism
Reza Rastmanesh, Lucky Krishnia, Manoj Kumar Kashyap
Summary: The COVID-19 pandemic has had various effects on people's lives, including changes in social behavior, healthcare procedures, and physiological responses. This has influenced medical studies, particularly in areas such as ophthalmology, sleep studies, cognitive research, and gender-related studies. There may be other COVID-19-related influences that are unrecognized in medical research. To address this, future studies should consider factors such as the severity of initial illness, timing of analysis, and the presence of a control group. Facemask-induced influences can confound the results of diabetes studies in multiple ways.
CLINICAL MEDICINE INSIGHTS-ENDOCRINOLOGY AND DIABETES
(2023)
Article
Hematology
Juan Esteban Garcia-Robledo, Cristina Valencia-Sanchez, Molly G. Knox, Brent P. Goodman, Allison C. Rosenthal, Bhavesh Patel, Januario E. Castro
Summary: Bedside sonographic measurement of optic nerve sheath diameter is helpful in diagnosing elevated intracranial pressure, and proved valuable in a case of immune effector cell-associated neurotoxicity syndrome. The patient showed wide optic nerve sheath diameters and bulging optic discs bilaterally. Prompt treatment resulted in a successful recovery with no long-term neurological deficits.
HEMATOLOGY REPORTS
(2023)
Review
Oncology
Anjali Kashyap, Greesham Tripathi, Avantika Tripathi, Rashmi Rao, Manju Kashyap, Anjali Bhat, Deepak Kumar, Anjali Rajhans, Pravindra Kumar, Darshan Shimoga Chandrashekar, Riaz Mahmood, Amjad Husain, Hatem Zayed, Alok Chandra Bharti, Manoj Kumar Kashyap
Summary: RNA splicing is a fundamental process that brings diversity at the transcriptome and proteome levels. Aberrant regulation of RNA splicing is associated with various diseases, including cancer. In hepatocellular carcinoma (HCC), multiple splicing events have been observed, which directly affect tumor progression and patient survival.