Jianjun Wu, Yinan Zhou, Hanqing Hu, Dawei Yang, Fan Yang
Type 2 diabetes mellitus (T2DM) is a common chronic disease that is strongly associated with cardiovascular risk. Long-term high blood glucose levels may induce cardiomyocyte apoptosis, cardiac dysfunction and suppress fetal cardiomyocyte proliferation. Recent epidemiological studies have shown a link between antioxidant carotenoids and T2DM, but a comprehensive longitudinal study of this association has not yet been conducted. We included participants with biological measurements for both serum cis-β-carotene and fasting glucose from NHANES (2001–2006). We divided the participants into quartiles according to serum cis-β-carotene levels and determined the association between these levels and glucose metabolism by using multivariable regression models adjusted for confounding factors. The mechanism through which β-carotene levels regulate plasma glucose levels was further investigated in vivo and in vitro. In addition, we performed a preliminary exploration of the effects of β-carotene on diabetic rats and primary cardiomyocytes. Higher cis-β-carotene (quartile 4) was associated with higher LDL-cholesterol levels but lower fasting blood glucose levels. However, T2DM rats subjected to β-carotene treatment showed diminished total triglycerides and LDL-cholesterol, and their β-carotene levels were associated with better cardiac function than that in the T2DM group (P<0.05). Moreover, β-carotene was found to be an important protective factor improving cardiac and mitochondrial function in diabetes. At non-cytotoxic doses, β-carotene clearly improved glucose uptake in insulin-resistant cells. Treatment with β-carotene increased GLUT4 and p-Akt expression, and attenuated the phosphorylation of IRS-1. Our data demonstrated that β-carotene improved cardiac mitochondria biogenesis in diabetes due to activation of PGC-1β. Our results indicate that β-carotene can be used to treat metabolic disorders through inhibition of the insulin-resistance pathway in diabetes.
{"title":"Effects of β-carotene on glucose metabolism dysfunction in humans and type 2 diabetic rats","authors":"Jianjun Wu, Yinan Zhou, Hanqing Hu, Dawei Yang, Fan Yang","doi":"10.15212/amm-2021-0009","DOIUrl":"https://doi.org/10.15212/amm-2021-0009","url":null,"abstract":"\u0000\u0000Type 2 diabetes mellitus (T2DM) is a common chronic disease that is strongly associated with cardiovascular risk. Long-term high blood glucose levels may induce cardiomyocyte apoptosis, cardiac dysfunction and suppress fetal cardiomyocyte proliferation. Recent epidemiological studies have shown a link between antioxidant carotenoids and T2DM, but a comprehensive longitudinal study of this association has not yet been conducted.\u0000\u0000\u0000\u0000We included participants with biological measurements for both serum cis-β-carotene and fasting glucose from NHANES (2001–2006). We divided the participants into quartiles according to serum cis-β-carotene levels and determined the association between these levels and glucose metabolism by using multivariable regression models adjusted for confounding factors. The mechanism through which β-carotene levels regulate plasma glucose levels was further investigated in vivo and in vitro. In addition, we performed a preliminary exploration of the effects of β-carotene on diabetic rats and primary cardiomyocytes.\u0000\u0000\u0000\u0000Higher cis-β-carotene (quartile 4) was associated with higher LDL-cholesterol levels but lower fasting blood glucose levels. However, T2DM rats subjected to β-carotene treatment showed diminished total triglycerides and LDL-cholesterol, and their β-carotene levels were associated with better cardiac function than that in the T2DM group (P<0.05). Moreover, β-carotene was found to be an important protective factor improving cardiac and mitochondrial function in diabetes. At non-cytotoxic doses, β-carotene clearly improved glucose uptake in insulin-resistant cells. Treatment with β-carotene increased GLUT4 and p-Akt expression, and attenuated the phosphorylation of IRS-1. Our data demonstrated that β-carotene improved cardiac mitochondria biogenesis in diabetes due to activation of PGC-1β.\u0000\u0000\u0000\u0000Our results indicate that β-carotene can be used to treat metabolic disorders through inhibition of the insulin-resistance pathway in diabetes.\u0000","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48253063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peptides are short chains of amino acids linked by peptide bonds. Many peptides and proteins are limited by their poor enzymatic stability and permeability across the intestinal epithelial membranes and/or blood-brain barrier (BBB). Parenteral administration of these peptides is unfavorable because of procedural complications and low patient compliance with treatments. Instead, oral delivery is the preferred route of administration because it allows for self-administration and has a high degree of patient acceptability and compliance. Oral delivery of these peptides poses a major challenge, because the peptide drug must overcome both the physical and biochemical barriers of the gastrointestinal tract and BBB. An oral drug delivery system is beneficial because it can protect peptide drugs against degradation and deliver them to the brain, where they exert their pharmacological actions. The use of active-targeting ligands and/or cell-penetrating peptides increases penetration and uptake across the BBB. This review focuses on the diverse combinations of drug delivery systems, active-targeting ligands, and cell-penetrating peptides used to deliver peptides to the brain.
{"title":"Ligands for oral delivery of peptides across the blood-brain-barrier","authors":"Murad Al Gailani, Mengyang Liu, Jingyuan Wen","doi":"10.15212/amm-2021-0007","DOIUrl":"https://doi.org/10.15212/amm-2021-0007","url":null,"abstract":"Peptides are short chains of amino acids linked by peptide bonds. Many peptides and proteins are limited by their poor enzymatic stability and permeability across the intestinal epithelial membranes and/or blood-brain barrier (BBB). Parenteral administration of these peptides is unfavorable because of procedural complications and low patient compliance with treatments. Instead, oral delivery is the preferred route of administration because it allows for self-administration and has a high degree of patient acceptability and compliance. Oral delivery of these peptides poses a major challenge, because the peptide drug must overcome both the physical and biochemical barriers of the gastrointestinal tract and BBB. An oral drug delivery system is beneficial because it can protect peptide drugs against degradation and deliver them to the brain, where they exert their pharmacological actions. The use of active-targeting ligands and/or cell-penetrating peptides increases penetration and uptake across the BBB. This review focuses on the diverse combinations of drug delivery systems, active-targeting ligands, and cell-penetrating peptides used to deliver peptides to the brain.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41339967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xudong Xie, Liangcong Hu, Hang Xue, Y. Xiong, Adriana C. Panayi, Ze Lin, Lang Chen, Chenchen Yan, Wu Zhou, B. Mi, Guohui Liu
The Coronavirus Disease 2019 (COVID-19) pandemic has been estimated to have claimed more than 6 million lives, and most deaths have been attributed to complications non-specific to the virus. Therefore, understanding and treating these complications are imperative. In this meta-analysis, we reviewed 181 studies published in early stages of the COVID-19 pandemic. We presented that the complications with high incidence among all COVID-19 cases were acute respiratory distress syndrome (ARDS, 18.52%), respiratory failure (16.54%), liver injury (14.13%) and multiple-organ dysfunction syndrome (MODS, 13.62%). Among patients who died, the most common complications were ARDS (84.10%), respiratory failure (78.75%) and respiratory injury (75.72%). Subsequently, we analyzed the risk factors for complications, and reviewed the currently available therapies according to complications and prognosis. To decrease the prevalence of COVID-19 complications and mortality, healthcare workers and patients should pay greater attention to the complications identified herein, particularly those occurring preclinically.
{"title":"Prognosis and treatment of complications associated with COVID-19: a systematic review and meta-analysis","authors":"Xudong Xie, Liangcong Hu, Hang Xue, Y. Xiong, Adriana C. Panayi, Ze Lin, Lang Chen, Chenchen Yan, Wu Zhou, B. Mi, Guohui Liu","doi":"10.15212/amm-2022-0002","DOIUrl":"https://doi.org/10.15212/amm-2022-0002","url":null,"abstract":"The Coronavirus Disease 2019 (COVID-19) pandemic has been estimated to have claimed more than 6 million lives, and most deaths have been attributed to complications non-specific to the virus. Therefore, understanding and treating these complications are imperative. In this meta-analysis, we reviewed 181 studies published in early stages of the COVID-19 pandemic. We presented that the complications with high incidence among all COVID-19 cases were acute respiratory distress syndrome (ARDS, 18.52%), respiratory failure (16.54%), liver injury (14.13%) and multiple-organ dysfunction syndrome (MODS, 13.62%). Among patients who died, the most common complications were ARDS (84.10%), respiratory failure (78.75%) and respiratory injury (75.72%). Subsequently, we analyzed the risk factors for complications, and reviewed the currently available therapies according to complications and prognosis. To decrease the prevalence of COVID-19 complications and mortality, healthcare workers and patients should pay greater attention to the complications identified herein, particularly those occurring preclinically.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46626711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Coronavirus disease 2019, responsible for a global pandemic, is caused by the severe acute respiratory syndrome coronavirus 2. Several vaccines have been developed and approved worldwide, particularly in China. As of Oct 17, 2021, four new coronavirus vaccines in China have been conditionally approved for marketing by the National Medical Products Administration, two of which have been authorized for emergency use in the Emergency Use Listing of the World Health Organization. Domestic vaccine R&D in China has relied on legal and regulatory support. This article summarizes the regulatory policy for vaccine development, review and approval. Vaccine approval laws have been continually improved, and regulations for special approval have been used to shorten the review time. China has coordinated pandemic-related needs, both domestically and with other countries, and made substantial progress in cooperative international anti-pandemic efforts.
{"title":"Regulatory lessons from China’s COVID-19 vaccines development and approval policies","authors":"Jingshu Yang, Yue Yang","doi":"10.15212/amm-2021-0008","DOIUrl":"https://doi.org/10.15212/amm-2021-0008","url":null,"abstract":"Coronavirus disease 2019, responsible for a global pandemic, is caused by the severe acute respiratory syndrome coronavirus 2. Several vaccines have been developed and approved worldwide, particularly in China. As of Oct 17, 2021, four new coronavirus vaccines in China have been conditionally approved for marketing by the National Medical Products Administration, two of which have been authorized for emergency use in the Emergency Use Listing of the World Health Organization. Domestic vaccine R&D in China has relied on legal and regulatory support. This article summarizes the regulatory policy for vaccine development, review and approval. Vaccine approval laws have been continually improved, and regulations for special approval have been used to shorten the review time. China has coordinated pandemic-related needs, both domestically and with other countries, and made substantial progress in cooperative international anti-pandemic efforts.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43212646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Caged xanthones are a class of natural compounds with approximately 200 members that are commonly isolated from the Garcinia genus in the Clusiaceae (formerly Guttiferae) family. They are often characterized by a notable 4-oxa-tricyclo[4.3.1.03,7]dec-2-one (caged) architecture with a common xanthone backbone. Because most caged xanthones have potent anticancer properties, they have become a target of interest in natural product chemistry. The unique chemical architectures and increasingly identified biological importance of these compounds have stimulated many studies and intense interest in their isolation, biological evaluation and mechanistic studies. This review summarizes recent progress and development in the chemistry and biological activity of caged Garcinia xanthones and of several compounds of non-Garcinia origin, from the years 2008 to 2021, providing an in-depth discussion of their structural diversity and medicinal potential. A preliminary discussion on structure-activity relationships is also provided.
{"title":"Structural diversity and biological activities of caged Garcinia xanthones: recent updates","authors":"Yeelin Phang, Changwu Zheng, Hongxi Xu","doi":"10.15212/amm-2022-0001","DOIUrl":"https://doi.org/10.15212/amm-2022-0001","url":null,"abstract":"Caged xanthones are a class of natural compounds with approximately 200 members that are commonly isolated from the Garcinia genus in the Clusiaceae (formerly Guttiferae) family. They are often characterized by a notable 4-oxa-tricyclo[4.3.1.03,7]dec-2-one (caged) architecture with a common xanthone backbone. Because most caged xanthones have potent anticancer properties, they have become a target of interest in natural product chemistry. The unique chemical architectures and increasingly identified biological importance of these compounds have stimulated many studies and intense interest in their isolation, biological evaluation and mechanistic studies. This review summarizes recent progress and development in the chemistry and biological activity of caged Garcinia xanthones and of several compounds of non-Garcinia origin, from the years 2008 to 2021, providing an in-depth discussion of their structural diversity and medicinal potential. A preliminary discussion on structure-activity relationships is also provided.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41902022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wan Najbah Nik Nabil, Zhichao Xi, Mengfan Liu, Yang Li, M. Yao, Taidong Liu, Q. Dong, Hongxi Xu
Quiescent cancer cells (QCCs) reversibly reside in G0 phase, thus allowing them to survive chemotherapy and radiotherapy, which generally target proliferating cells. Surviving QCCs may re-proliferate, and consequently result in cancer progression, recurrence, and metastasis. Therefore, understanding the key players governing QCC survival and activation is crucial for developing QCC-targeting agents. This review presents an overview of (1) the mechanisms underlying the regulation of QCC status and (2) recent advances in the development of QCC-targeting therapeutic agents and their underlying mechanisms. The development of effective therapeutic modalities that target QCCs may enable new cancer treatments to prevent cancer progression and recurrence.
{"title":"Advances in therapeutic agents targeting quiescent cancer cells","authors":"Wan Najbah Nik Nabil, Zhichao Xi, Mengfan Liu, Yang Li, M. Yao, Taidong Liu, Q. Dong, Hongxi Xu","doi":"10.15212/amm-2021-0005","DOIUrl":"https://doi.org/10.15212/amm-2021-0005","url":null,"abstract":"Quiescent cancer cells (QCCs) reversibly reside in G0 phase, thus allowing them to survive chemotherapy and radiotherapy, which generally target proliferating cells. Surviving QCCs may re-proliferate, and consequently result in cancer progression, recurrence, and metastasis. Therefore, understanding the key players governing QCC survival and activation is crucial for developing QCC-targeting agents. This review presents an overview of (1) the mechanisms underlying the regulation of QCC status and (2) recent advances in the development of QCC-targeting therapeutic agents and their underlying mechanisms. The development of effective therapeutic modalities that target QCCs may enable new cancer treatments to prevent cancer progression and recurrence.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45862364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maintaining neuronal integrity and functions requires precise mechanisms controlling organelle and protein quality. Alzheimer's disease (AD) is characterized by functional defects in the clearance and recycling of intracellular components. As such, neuronal homeostasis involves autophagy, mitophagy, and apoptosis. Compromised activity in these cellular processes may cause pathological phenotypes of AD. Dysfunction of mitochondria is one of the hallmarks of AD. Mitophagy is a critical mitochondria quality control system, and the impaired mitophagy is observed in AD. Myeloid cell leukemia 1 (MCL1), a member of the pro-survival B-cell lymphoma protein 2 (BCL2) family, is a mitochondria-targeted protein that contributes to maintaining mitochondrial integrity. Mcl1 knockout mice display peri-implantation lethality. The studies on conditional Mcl1 knockout mice demonstrate that MCL1 plays a central role in neurogenesis and neuronal survival during brain development. Accumulating evidence reveals the critical role of MCL1 as a regulator of neuronal autophagy, mitophagy, and survival. In this review, we discuss the emerging neuroprotective function of MCL1 and how dysregulation of MCL1 signaling is involved in the pathogenesis of AD. As the pro-survival BCL2 family of proteins are promising targets of pharmacological intervention with BH3 mimetic drugs, we also discuss the promise of MCL1-targeting therapy in AD.
{"title":"The regulation of neuronal autophagy and cell survival by MCL1 in Alzheimer's disease.","authors":"A. Rezaeian, Wenyi Wei, H. Inuzuka","doi":"10.15212/amm-2021-0002","DOIUrl":"https://doi.org/10.15212/amm-2021-0002","url":null,"abstract":"Maintaining neuronal integrity and functions requires precise mechanisms controlling organelle and protein quality. Alzheimer's disease (AD) is characterized by functional defects in the clearance and recycling of intracellular components. As such, neuronal homeostasis involves autophagy, mitophagy, and apoptosis. Compromised activity in these cellular processes may cause pathological phenotypes of AD. Dysfunction of mitochondria is one of the hallmarks of AD. Mitophagy is a critical mitochondria quality control system, and the impaired mitophagy is observed in AD. Myeloid cell leukemia 1 (MCL1), a member of the pro-survival B-cell lymphoma protein 2 (BCL2) family, is a mitochondria-targeted protein that contributes to maintaining mitochondrial integrity. Mcl1 knockout mice display peri-implantation lethality. The studies on conditional Mcl1 knockout mice demonstrate that MCL1 plays a central role in neurogenesis and neuronal survival during brain development. Accumulating evidence reveals the critical role of MCL1 as a regulator of neuronal autophagy, mitophagy, and survival. In this review, we discuss the emerging neuroprotective function of MCL1 and how dysregulation of MCL1 signaling is involved in the pathogenesis of AD. As the pro-survival BCL2 family of proteins are promising targets of pharmacological intervention with BH3 mimetic drugs, we also discuss the promise of MCL1-targeting therapy in AD.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":"1 1 1","pages":"42-55"},"PeriodicalIF":0.0,"publicationDate":"2022-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46820979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neurodegenerative diseases (NDs) are characteristic with progression of neuron degeneration, resulting in dysfunction of cognition and mobility. Many neurodegenerative diseases are because of proteinopathies that results from unusual protein accumulations and aggregations. The aggregation of misfolded proteins like β-amyloid, α-synuclein, tau, and polyglutamates are hallmarked in Alzheimer's disease (AD), which are undruggable targets, and usually do not respond to conventional small-molecule agents. Therefore, developing novel technology and strategy for reducing the levels of protein aggregates would be critical for treatment of AD. Recently, the emerging proteolysis targeting chimeras (PRPTACs) technology has been significantly considered for artificial and selective degradation of aberrant target proteins. These engineered bifunctional molecules engage target proteins to be degraded by either the cellular degradation machinery in the ubiquitin-proteasome system (UPS) or via the autophagy-lysosome degradation pathway. Although the application of PROTACs technology is preferable than oligonucleotide and antibodies for treatment of NDs, many limitations such as their pharmacokinetic properties, tissue distribution and cell permeabilities, still need to be corrected. Herein, we review the recent advances in PROTACs technology with their limitation for pharmaceutical targeting of aberrant proteins involved in Alzheimer's diseases. We also review therapeutic potential of dysregulated signaling such as PI3K/AKT/mTOR axis for the management of AD.
{"title":"PROTACs technology for treatment of Alzheimer's disease: Advances and perspectives.","authors":"H. Inuzuka, Jing Liu, Wenyi Wei, A. Rezaeian","doi":"10.15212/amm-2021-0001","DOIUrl":"https://doi.org/10.15212/amm-2021-0001","url":null,"abstract":"Neurodegenerative diseases (NDs) are characteristic with progression of neuron degeneration, resulting in dysfunction of cognition and mobility. Many neurodegenerative diseases are because of proteinopathies that results from unusual protein accumulations and aggregations. The aggregation of misfolded proteins like β-amyloid, α-synuclein, tau, and polyglutamates are hallmarked in Alzheimer's disease (AD), which are undruggable targets, and usually do not respond to conventional small-molecule agents. Therefore, developing novel technology and strategy for reducing the levels of protein aggregates would be critical for treatment of AD. Recently, the emerging proteolysis targeting chimeras (PRPTACs) technology has been significantly considered for artificial and selective degradation of aberrant target proteins. These engineered bifunctional molecules engage target proteins to be degraded by either the cellular degradation machinery in the ubiquitin-proteasome system (UPS) or via the autophagy-lysosome degradation pathway. Although the application of PROTACs technology is preferable than oligonucleotide and antibodies for treatment of NDs, many limitations such as their pharmacokinetic properties, tissue distribution and cell permeabilities, still need to be corrected. Herein, we review the recent advances in PROTACs technology with their limitation for pharmaceutical targeting of aberrant proteins involved in Alzheimer's diseases. We also review therapeutic potential of dysregulated signaling such as PI3K/AKT/mTOR axis for the management of AD.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":"1 1 1","pages":"24-41"},"PeriodicalIF":0.0,"publicationDate":"2022-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48957606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Donglei Shi, Wenwen Liu, Guangwei Wang, Yuan Guo, Jian Li
Aging is a time-dependent decline in physiological function that affects most organisms and is the major risk factor for many non-communicable diseases. The early diagnosis of aging is critical for the treatment of aging and aging-related diseases. In recent years, extensive efforts have attempted to accurately diagnose aging. To date, multiple types of fluorescent probes for various age-related biomarkers have been developed, with the aims of achieving rapid, precise diagnosis of the aging process and evaluating the efficacy of anti-aging drugs. This review summarizes recent research progress in small-molecule fluorescence-based probes for aging diagnosis, and further discusses the challenges and opportunities in this field.
{"title":"Small-molecule fluorescence-based probes for aging diagnosis","authors":"Donglei Shi, Wenwen Liu, Guangwei Wang, Yuan Guo, Jian Li","doi":"10.15212/amm-2021-0004","DOIUrl":"https://doi.org/10.15212/amm-2021-0004","url":null,"abstract":"Aging is a time-dependent decline in physiological function that affects most organisms and is the major risk factor for many non-communicable diseases. The early diagnosis of aging is critical for the treatment of aging and aging-related diseases. In recent years, extensive efforts have attempted to accurately diagnose aging. To date, multiple types of fluorescent probes for various age-related biomarkers have been developed, with the aims of achieving rapid, precise diagnosis of the aging process and evaluating the efficacy of anti-aging drugs. This review summarizes recent research progress in small-molecule fluorescence-based probes for aging diagnosis, and further discusses the challenges and opportunities in this field.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45580841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mouse double minute 2 (MDM2) is an E3 ubiquitin ligase which effectively degrades tumor suppressor p53. In the past two decades, many MDM2 inhibitors that disrupt the MDM2-p53 binding have been discovered and developed. Given that the MDM2-p53 forms auto-regulatory loop in which p53 is a substrate of MDM2 for targeted degradation, while MDM2 is a p53 target for transcriptional upregulation, these MDM2 inhibitors have limited efficacy due to p53 degradation by accumulated MDM2 upon rapid in vivo clearance of the MDM2 inhibitors. Fortunately, proteolysis targeting chimeras (PROTACs), a novel therapeutic strategy, overcome the limitations of MDM2 inhibitors. Some of MDM2 inhibitors developed in the past two decades have been used in PROTAC technology for two applications: 1) as component 1 to bind with endogenous MDM2 as a target for PROTAC-based degradation of MDM2; and 2) as component 2 to bind with endogenous MDM2 as a PROTAC E3 ligand for PROTAC-based degradation of other oncogenic proteins. In this review, we summarize current progress in the discovery and development of MDM2-based PROTAC drugs with future perspectives and challenges for their applications in effective treatment of human cancer.
{"title":"PROTAC Degraders with Ligands Recruiting MDM2 E3 Ubiquitin Ligase: An Updated Perspective.","authors":"Xin Han, Wenyi Wei, Yi Sun","doi":"10.15212/amm-2022-0010","DOIUrl":"https://doi.org/10.15212/amm-2022-0010","url":null,"abstract":"<p><p>Mouse double minute 2 (MDM2) is an E3 ubiquitin ligase which effectively degrades tumor suppressor p53. In the past two decades, many MDM2 inhibitors that disrupt the MDM2-p53 binding have been discovered and developed. Given that the MDM2-p53 forms auto-regulatory loop in which p53 is a substrate of MDM2 for targeted degradation, while MDM2 is a p53 target for transcriptional upregulation, these MDM2 inhibitors have limited efficacy due to p53 degradation by accumulated MDM2 upon rapid <i>in vivo</i> clearance of the MDM2 inhibitors. Fortunately, proteolysis targeting chimeras (PROTACs), a novel therapeutic strategy, overcome the limitations of MDM2 inhibitors. Some of MDM2 inhibitors developed in the past two decades have been used in PROTAC technology for two applications: 1) as component 1 to bind with endogenous MDM2 as a target for PROTAC-based degradation of MDM2; and 2) as component 2 to bind with endogenous MDM2 as a PROTAC E3 ligand for PROTAC-based degradation of other oncogenic proteins. In this review, we summarize current progress in the discovery and development of MDM2-based PROTAC drugs with future perspectives and challenges for their applications in effective treatment of human cancer.</p>","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":"1 2","pages":"244-259"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9211018/pdf/nihms-1812315.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9628419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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