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Article ; Online: Antiaging Strategies and Remedies: A Landscape of Research Progress and Promise.

Tenchov, Rumiana / Sasso, Janet M / Wang, Xinmei / Zhou, Qiongqiong Angela

ACS chemical neuroscience

2024 Volume 15, Issue 3, Page(s) 408–446

Abstract: Aging is typified by a gradual loss of physiological fitness and accumulation of cellular damage, leading to deteriorated functions and enhanced vulnerability to diseases. Antiaging research has a long history throughout civilization, with many efforts ... ...

Abstract	Aging is typified by a gradual loss of physiological fitness and accumulation of cellular damage, leading to deteriorated functions and enhanced vulnerability to diseases. Antiaging research has a long history throughout civilization, with many efforts put forth to understand and prevent the effects of aging. Multiple strategies aiming to promote healthy aging and extend the lifespan have been developed including lifestyle adjustments, medical treatments, and social programs. A multitude of antiaging medicines and remedies have also been explored. Here, we use data from the CAS Content Collection to analyze the publication landscape of recent research related to antiaging strategies and treatments. We review the recent advances and delineate trends in research headway of antiaging knowledge and practice across time, geography, and development pipelines. We further assess the state-of-the-art antiaging approaches and explore their correlations with age-related diseases. The landscape of antiaging drugs has been outlined and explored. Well-recognized and novel, currently evaluated antiaging agents have also been summarized. Finally, we review clinical applications of antiaging products with their development pipelines. The objective of this review is to summarize current knowledge on preventive strategies and treatment remedies in the field of aging, to outline challenges and evaluate growth opportunities, in order to further efforts to solve the problems that remain.
Language	English
Publishing date	2024-01-12
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1948-7193
ISSN (online)	1948-7193
DOI	10.1021/acschemneuro.3c00532
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: PEGylated Lipid Nanoparticle Formulations: Immunological Safety and Efficiency Perspective.

Tenchov, Rumiana / Sasso, Janet M / Zhou, Qiongqiong Angela

Bioconjugate chemistry

2023 Volume 34, Issue 6, Page(s) 941–960

Abstract: Lipid nanoparticles (LNPs) have been recognized as efficient vehicles to transport a large variety of therapeutics. Currently in the spotlight as important constituents of the COVID-19 mRNA vaccines, LNPs play a significant role in protecting and ... ...

Abstract	Lipid nanoparticles (LNPs) have been recognized as efficient vehicles to transport a large variety of therapeutics. Currently in the spotlight as important constituents of the COVID-19 mRNA vaccines, LNPs play a significant role in protecting and transporting mRNA to cells. As one of their key constituents, polyethylene glycol (PEG)-lipid conjugates are important in defining LNP physicochemical characteristics and biological activity. PEGylation has proven particularly efficient in conferring longer systemic circulation of LNPs, thus greatly improving their pharmacokinetics and efficiency. Along with revealing the benefits of PEG conjugates, studies have revealed unexpected immune reactions against PEGylated nanocarriers such as accelerated blood clearance (ABC), involving the production of anti-PEG antibodies at initial injection, which initiates accelerated blood clearance upon subsequent injections, as well as a hypersensitivity reaction referred to as complement activation-related pseudoallergy (CARPA). Further, data have been accumulated indicating consistent yet sometimes controversial correlations between various structural parameters of the PEG-lipids, the properties of the PEGylated LNPs, and the magnitude of the observed adverse effects. Detailed knowledge and comprehension of such correlations are of foremost importance in the efforts to diminish and eliminate the undesirable immune reactions and improve the safety and efficiency of the PEGylated medicines. Here, we present an overview based on analysis of data from the CAS Content Collection regarding the PEGylated LNP immunogenicity and overall safety concerns. A comprehensive summary has been compiled outlining how various structural parameters of the PEG-lipids affect the immune responses and activities of the LNPs, with regards to their efficiency in drug delivery. This Review is thus intended to serve as a helpful resource in understanding the current knowledge in the field, in an effort to further solve the remaining challenges and to achieve full potential.
MeSH term(s)	Humans ; COVID-19 ; Liposomes/chemistry ; Polyethylene Glycols/chemistry ; Nanoparticles/chemistry ; Lipids/chemistry
Chemical Substances	Lipid Nanoparticles ; Liposomes ; Polyethylene Glycols (3WJQ0SDW1A) ; Lipids
Language	English
Publishing date	2023-05-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1024041-x
ISSN	1520-4812 ; 1043-1802
ISSN (online)	1520-4812
ISSN	1043-1802
DOI	10.1021/acs.bioconjchem.3c00174
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Article ; Online: Aging Hallmarks and Progression and Age-Related Diseases: A Landscape View of Research Advancement.

Tenchov, Rumiana / Sasso, Janet M / Wang, Xinmei / Zhou, Qiongqiong Angela

ACS chemical neuroscience

2023 Volume 15, Issue 1, Page(s) 1–30

Abstract: Aging is a dynamic, time-dependent process that is characterized by a gradual accumulation of cell damage. Continual functional decline in the intrinsic ability of living organisms to accurately regulate homeostasis leads to increased susceptibility and ... ...

Abstract	Aging is a dynamic, time-dependent process that is characterized by a gradual accumulation of cell damage. Continual functional decline in the intrinsic ability of living organisms to accurately regulate homeostasis leads to increased susceptibility and vulnerability to diseases. Many efforts have been put forth to understand and prevent the effects of aging. Thus, the major cellular and molecular hallmarks of aging have been identified, and their relationships to age-related diseases and malfunctions have been explored. Here, we use data from the CAS Content Collection to analyze the publication landscape of recent aging-related research. We review the advances in knowledge and delineate trends in research advancements on aging factors and attributes across time and geography. We also review the current concepts related to the major aging hallmarks on the molecular, cellular, and organismic level, age-associated diseases, with attention to brain aging and brain health, as well as the major biochemical processes associated with aging. Major age-related diseases have been outlined, and their correlations with the major aging features and attributes are explored. We hope this review will be helpful for apprehending the current knowledge in the field of aging mechanisms and progression, in an effort to further solve the remaining challenges and fulfill its potential.
MeSH term(s)	Cellular Senescence/physiology ; Age Factors
Language	English
Publishing date	2023-12-14
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1948-7193
ISSN (online)	1948-7193
DOI	10.1021/acschemneuro.3c00531
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Article ; Online: Molecular Glues: The Adhesive Connecting Targeted Protein Degradation to the Clinic.

Sasso, Janet M / Tenchov, Rumiana / Wang, DaSheng / Johnson, Linda S / Wang, Xinmei / Zhou, Qiongqiong Angela

Biochemistry

2022 Volume 62, Issue 3, Page(s) 601–623

Abstract: Targeted protein degradation is a rapidly exploding drug discovery strategy that uses small molecules to recruit disease-causing proteins for rapid destruction mainly via the ubiquitin-proteasome pathway. It shows great potential for treating diseases ... ...

Abstract	Targeted protein degradation is a rapidly exploding drug discovery strategy that uses small molecules to recruit disease-causing proteins for rapid destruction mainly via the ubiquitin-proteasome pathway. It shows great potential for treating diseases such as cancer and infectious, inflammatory, and neurodegenerative diseases, especially for those with "undruggable" pathogenic protein targets. With the recent rise of the "molecular glue" type of protein degraders, which tighten and simplify the connection of an E3 ligase with a disease-causing protein for ubiquitination and subsequent degradation, new therapies for unmet medical needs are being designed and developed. Here we use data from the CAS Content Collection and the publication landscape of recent research on targeted protein degraders to provide insights into these molecules, with a special focus on molecular glues. We also outline the advantages of the molecular glues and summarize the advances in drug discovery practices for molecular glue degraders. We further provide a thorough review of drug candidates in targeted protein degradation through E3 ligase recruitment. Finally, we highlight the progression of molecular glues in drug discovery pipelines and their targeted diseases. Overall, our paper provides a comprehensive reference to support the future development of molecular glues in medicine.
MeSH term(s)	Proteolysis ; Proteins/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination ; Drug Discovery ; Proteasome Endopeptidase Complex/metabolism
Chemical Substances	Proteins ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2022-07-20
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1108-3
ISSN	1520-4995 ; 0006-2960
ISSN (online)	1520-4995
ISSN	0006-2960
DOI	10.1021/acs.biochem.2c00245
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Article ; Online: Exosomes─Nature's Lipid Nanoparticles, a Rising Star in Drug Delivery and Diagnostics.

Tenchov, Rumiana / Sasso, Janet M / Wang, Xinmei / Liaw, Wen-Shing / Chen, Chun-An / Zhou, Qiongqiong Angela

ACS nano

2022 Volume 16, Issue 11, Page(s) 17802–17846

Abstract: Exosomes are a subgroup of nanosized extracellular vesicles enclosed by a lipid bilayer membrane and secreted by most eukaryotic cells. They represent a route of intercellular communication and participate in a wide variety of physiological and ... ...

Abstract	Exosomes are a subgroup of nanosized extracellular vesicles enclosed by a lipid bilayer membrane and secreted by most eukaryotic cells. They represent a route of intercellular communication and participate in a wide variety of physiological and pathological processes. The biological roles of exosomes rely on their bioactive cargos, including proteins, nucleic acids, and lipids, which are delivered to target cells. Their distinctive properties─innate stability, low immunogenicity, biocompatibility, and good biomembrane penetration capacity─allow them to function as superior natural nanocarriers for efficient drug delivery. Another notably favorable clinical application of exosomes is in diagnostics. They hold various biomolecules from host cells, which are indicative of pathophysiological conditions; therefore, they are considered vital for biomarker discovery in clinical diagnostics. Here, we use data from the CAS Content Collection and provide a landscape overview of the current state and delineate trends in research advancement on exosome applications in therapeutics and diagnostics across time, geography, composition, cargo loading, and development pipelines. We discuss exosome composition and pathway, from their biogenesis and secretion from host cells to recipient cell uptake. We assess methods for exosome isolation and purification, their clinical applications in therapy and diagnostics, their development pipelines, the exploration goals of the companies, the assortment of diseases they aim to treat, development stages of their research, and publication trends. We hope this review will be useful for understanding the current knowledge in the field of medical applications of exosomes, in an effort to further solve the remaining challenges in fulfilling their potential.
MeSH term(s)	Drug Delivery Systems/methods ; Nanoparticles ; Liposomes/metabolism ; Exosomes/metabolism
Chemical Substances	Lipid Nanoparticles ; Liposomes
Language	English
Publishing date	2022-11-10
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1936-086X
ISSN (online)	1936-086X
DOI	10.1021/acsnano.2c08774
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Article ; Online: Gut Microbiome-Brain Alliance: A Landscape View into Mental and Gastrointestinal Health and Disorders.

Sasso, Janet M / Ammar, Ramy M / Tenchov, Rumiana / Lemmel, Steven / Kelber, Olaf / Grieswelle, Malte / Zhou, Qiongqiong Angela

ACS chemical neuroscience

2023 Volume 14, Issue 10, Page(s) 1717–1763

Abstract: Gut microbiota includes a vast collection of microorganisms residing within the gastrointestinal tract. It is broadly recognized that the gut and brain are in constant bidirectional communication, of which gut microbiota and its metabolic production are ... ...

Abstract	Gut microbiota includes a vast collection of microorganisms residing within the gastrointestinal tract. It is broadly recognized that the gut and brain are in constant bidirectional communication, of which gut microbiota and its metabolic production are a major component, and form the so-called gut microbiome-brain axis. Disturbances of microbiota homeostasis caused by imbalance in their functional composition and metabolic activities, known as dysbiosis, cause dysregulation of these pathways and trigger changes in the blood-brain barrier permeability, thereby causing pathological malfunctions, including neurological and functional gastrointestinal disorders. In turn, the brain can affect the structure and function of gut microbiota through the autonomic nervous system by regulating gut motility, intestinal transit and secretion, and gut permeability. Here, we examine data from the CAS Content Collection, the largest collection of published scientific information, and analyze the publication landscape of recent research. We review the advances in knowledge related to the human gut microbiome, its complexity and functionality, its communication with the central nervous system, and the effect of the gut microbiome-brain axis on mental and gut health. We discuss correlations between gut microbiota composition and various diseases, specifically gastrointestinal and mental disorders. We also explore gut microbiota metabolites with regard to their impact on the brain and gut function and associated diseases. Finally, we assess clinical applications of gut-microbiota-related substances and metabolites with their development pipelines. We hope this review can serve as a useful resource in understanding the current knowledge on this emerging field in an effort to further solving of the remaining challenges and fulfilling its potential.
MeSH term(s)	Humans ; Gastrointestinal Microbiome/physiology ; Brain/metabolism ; Central Nervous System/physiology ; Gastrointestinal Tract ; Microbiota/physiology
Language	English
Publishing date	2023-05-08
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1948-7193
ISSN (online)	1948-7193
DOI	10.1021/acschemneuro.3c00127
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The Evolving Landscape of Antibody-Drug Conjugates: In Depth Analysis of Recent Research Progress.

Sasso, Janet M / Tenchov, Rumiana / Bird, Robert / Iyer, Kavita A / Ralhan, Krittika / Rodriguez, Yacidzohara / Zhou, Qiongqiong Angela

Bioconjugate chemistry

2023 Volume 34, Issue 11, Page(s) 1951–2000

Abstract: Antibody-drug conjugates (ADCs) are targeted immunoconjugate constructs that integrate the potency of cytotoxic drugs with the selectivity of monoclonal antibodies, minimizing damage to healthy cells and reducing systemic toxicity. Their design allows ... ...

Abstract	Antibody-drug conjugates (ADCs) are targeted immunoconjugate constructs that integrate the potency of cytotoxic drugs with the selectivity of monoclonal antibodies, minimizing damage to healthy cells and reducing systemic toxicity. Their design allows for higher doses of the cytotoxic drug to be administered, potentially increasing efficacy. They are currently among the most promising drug classes in oncology, with efforts to expand their application for nononcological indications and in combination therapies. Here we provide a detailed overview of the recent advances in ADC research and consider future directions and challenges in promoting this promising platform to widespread therapeutic use. We examine data from the CAS Content Collection, the largest human-curated collection of published scientific information, and analyze the publication landscape of recent research to reveal the exploration trends in published documents and to provide insights into the scientific advances in the area. We also discuss the evolution of the key concepts in the field, the major technologies, and their development pipelines with company research focuses, disease targets, development stages, and publication and investment trends. A comprehensive concept map has been created based on the documents in the CAS Content Collection. We hope that this report can serve as a useful resource for understanding the current state of knowledge in the field of ADCs and the remaining challenges to fulfill their potential.
MeSH term(s)	Humans ; Immunoconjugates/therapeutic use ; Antineoplastic Agents/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Neoplasms/drug therapy
Chemical Substances	Immunoconjugates ; Antineoplastic Agents ; Antibodies, Monoclonal
Language	English
Publishing date	2023-10-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1024041-x
ISSN	1520-4812 ; 1043-1802
ISSN (online)	1520-4812
ISSN	1043-1802
DOI	10.1021/acs.bioconjchem.3c00374
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Article ; Online: The Progress and Promise of RNA Medicine─An Arsenal of Targeted Treatments.

Sasso, Janet M / Ambrose, Barbara J B / Tenchov, Rumiana / Datta, Ruchira S / Basel, Matthew T / DeLong, Robert K / Zhou, Qiongqiong Angela

Journal of medicinal chemistry

2022 Volume 65, Issue 10, Page(s) 6975–7015

Abstract: In the past decade, there has been a shift in research, clinical development, and commercial activity to exploit the many physiological roles of RNA for use in medicine. With the rapid success in the development of lipid-RNA nanoparticles for mRNA ... ...

Abstract	In the past decade, there has been a shift in research, clinical development, and commercial activity to exploit the many physiological roles of RNA for use in medicine. With the rapid success in the development of lipid-RNA nanoparticles for mRNA vaccines against COVID-19 and with several approved RNA-based drugs, RNA has catapulted to the forefront of drug research. With diverse functions beyond the role of mRNA in producing antigens or therapeutic proteins, many classes of RNA serve regulatory roles in cells and tissues. These RNAs have potential as new therapeutics, with RNA itself serving as either a drug or a target. Here, based on the CAS Content Collection, we provide a landscape view of the current state and outline trends in RNA research in medicine across time, geography, therapeutic pipelines, chemical modifications, and delivery mechanisms.
MeSH term(s)	COVID-19 Vaccines ; Humans ; RNA ; RNA, Messenger/metabolism ; SARS-CoV-2 ; COVID-19 Drug Treatment
Chemical Substances	COVID-19 Vaccines ; RNA, Messenger ; RNA (63231-63-0)
Language	English
Publishing date	2022-05-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.2c00024
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Zs.MB 1: Show issues

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Article ; Online: Messenger RNA-Based Therapeutics and Vaccines: What's beyond COVID-19?

Li, Dongqiao / Liu, Cynthia / Li, Yingzhu / Tenchov, Rumiana / Sasso, Janet M / Zhang, Di / Li, Dan / Zou, Lixue / Wang, Xuezhao / Zhou, Qiongqiong

ACS pharmacology & translational science

2023 Volume 6, Issue 7, Page(s) 943–969

Abstract: With the rapid success in the development of mRNA vaccines against COVID-19 and with a number of mRNA-based drugs ahead in the pipelines, mRNA has catapulted to the forefront of drug research, demonstrating its substantial effectiveness against a broad ... ...

Abstract	With the rapid success in the development of mRNA vaccines against COVID-19 and with a number of mRNA-based drugs ahead in the pipelines, mRNA has catapulted to the forefront of drug research, demonstrating its substantial effectiveness against a broad range of diseases. As the recent global pandemic gradually fades, we cannot stop thinking about what the world has gained: the realization and validation of the power of mRNA in modern medicine. A significant amount of research has now been concentrated on developing mRNA drugs and vaccine platforms against infectious and immune diseases, cancer, and other debilitating diseases and has demonstrated encouraging results. Here, based on the CAS Content Collection, we provide a landscape view of the current state, outline trends in the research and development of mRNA therapeutics and vaccines, and highlight some notable patents focusing on mRNA therapeutics, vaccines, and delivery systems. Analysis of diseases disclosed in patents also reveals highly investigated diseases for treatments with these medicines. Finally, we provide information about mRNA therapeutics and vaccines in clinical trials. We hope this Review will be useful for understanding the current knowledge in the field of mRNA medicines and will assist in efforts to solve its remaining challenges and revolutionize the treatment of human diseases.
Language	English
Publishing date	2023-07-03
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2575-9108
ISSN (online)	2575-9108
DOI	10.1021/acsptsci.3c00047
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Article: Assay Techniques and Test Development for COVID-19 Diagnosis.

Carter, Linda J / Garner, Linda V / Smoot, Jeffrey W / Li, Yingzhu / Zhou, Qiongqiong / Saveson, Catherine J / Sasso, Janet M / Gregg, Anne C / Soares, Divya J / Beskid, Tiffany R / Jervey, Susan R / Liu, Cynthia

ACS central science

2020 Volume 6, Issue 5, Page(s) 591–605

Keywords	covid19
Language	English
Publishing date	2020-04-30
Publishing country	United States
Document type	News
ISSN	2374-7943
ISSN	2374-7943
DOI	10.1021/acscentsci.0c00501
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