The compound 7-ethyl-10-hydroxy-camptothecin (SN38) is a broad-spectrum antitumor agent whose applications are greatly limited by its poor solubility. Therefore, irinotecan, the hydrophilic derived prodrug of SN38, has been developed as the commercial formulation Campto® for colorectal cancer. However, only 1% to 0.1% of irinotecan is converted to active SN38 in vivo, thus leading to unsatisfactory antitumor activity in clinical settings. Herein, we report a smart stimuli-responsive SN38 prodrug nanoassembly for efficient cancer therapy. First, SN38 was conjugated with an endogenous lipid, cholesterol (CST), via a redox dual-responsive disulfide bond (namely SN38-SS-CST). The prodrug self-assembled into uniform prodrug nanoassemblies with good colloidal stability and ultrahigh drug loading. SN38-SS-CST NPs released sufficient SN38 in the redox environments of tumor cells but remained intact in normal tissues. Finally, SN38-SS-CST NPs potently inhibited the growth of colon cancer without causing systemic toxicity, thus indicating their promise as a translational chemotherapeutic nanomedicine.
{"title":"Smart stimuli-responsive carrier-free nanoassembly of SN38 prodrug as efficient chemotherapeutic nanomedicine","authors":"Guanting Li, Qianhui Jin, Fengli Xia, Shuwen Fu, Xuanbo Zhang, Hongying Xiao, Chutong Tian, Qingzhi Lv, J. Sun, Zhonggui He, Bingjun Sun","doi":"10.15212/amm-2023-0003","DOIUrl":"https://doi.org/10.15212/amm-2023-0003","url":null,"abstract":"The compound 7-ethyl-10-hydroxy-camptothecin (SN38) is a broad-spectrum antitumor agent whose applications are greatly limited by its poor solubility. Therefore, irinotecan, the hydrophilic derived prodrug of SN38, has been developed as the commercial formulation Campto® for colorectal cancer. However, only 1% to 0.1% of irinotecan is converted to active SN38 in vivo, thus leading to unsatisfactory antitumor activity in clinical settings. Herein, we report a smart stimuli-responsive SN38 prodrug nanoassembly for efficient cancer therapy. First, SN38 was conjugated with an endogenous lipid, cholesterol (CST), via a redox dual-responsive disulfide bond (namely SN38-SS-CST). The prodrug self-assembled into uniform prodrug nanoassemblies with good colloidal stability and ultrahigh drug loading. SN38-SS-CST NPs released sufficient SN38 in the redox environments of tumor cells but remained intact in normal tissues. Finally, SN38-SS-CST NPs potently inhibited the growth of colon cancer without causing systemic toxicity, thus indicating their promise as a translational chemotherapeutic nanomedicine.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48099874","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}
Proteolysis-targeting chimeras (PROTACs), a novel targeted protein degradation technology for potential clinical drug discovery, is composed of a protein-targeting ligand covalently linked to an E3 ligase ligand. Through recruiting E3 ligase to target proteins, PROTACs elicit ubiquitination and subsequent degradation of targets via the ubiquitin-proteasome system. In the past few decades, molecular docking and virtual screening have emerged as an efficient strategy in drug discovery for identifying compounds from a large database of chemical structures. For PROTACs, molecular docking accurately simulates the protein-PROTAC-E3 ternary complex, thus greatly accelerating structure-activity-relationship analysis, and improving ligand affinity and selectivity. In this review, we summarize recent efforts in the application of molecular docking and virtual screening for PROTAC drug discovery. To date, approximately nine target proteins and twelve PROTACs have been successfully developed through molecular docking and virtual screening. Finally, the potential challenges of molecular docking and virtual screening-based PROTACs are discussed.
{"title":"Computational strategies for PROTAC drug discovery","authors":"J. Wu, Wanhe Wang, Chung-Hang Leung","doi":"10.15212/amm-2022-0041","DOIUrl":"https://doi.org/10.15212/amm-2022-0041","url":null,"abstract":"Proteolysis-targeting chimeras (PROTACs), a novel targeted protein degradation technology for potential clinical drug discovery, is composed of a protein-targeting ligand covalently linked to an E3 ligase ligand. Through recruiting E3 ligase to target proteins, PROTACs elicit ubiquitination and subsequent degradation of targets via the ubiquitin-proteasome system. In the past few decades, molecular docking and virtual screening have emerged as an efficient strategy in drug discovery for identifying compounds from a large database of chemical structures. For PROTACs, molecular docking accurately simulates the protein-PROTAC-E3 ternary complex, thus greatly accelerating structure-activity-relationship analysis, and improving ligand affinity and selectivity. In this review, we summarize recent efforts in the application of molecular docking and virtual screening for PROTAC drug discovery. To date, approximately nine target proteins and twelve PROTACs have been successfully developed through molecular docking and virtual screening. Finally, the potential challenges of molecular docking and virtual screening-based PROTACs are discussed.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47173202","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}
Hanmei Li, Rui Gou, Jiaying Liao, Yao Wang, Rui Qu, Qi Tang, Jingyao Gan, Liang Zou, Sanjun Shi
Rheumatoid arthritis is a systemic inflammatory disease that can lead to articular cartilage destruction and periarticular bone erosion, thus ultimately compromising joint integrity and function. Anti-inflammatory drugs and biological agents are commonly used to treat rheumatoid arthritis, but they cannot selectively target inflamed joints, because of their systemic mechanisms, short half-lives and low bioavailability. Consequently, these agents must be used at high doses and delivered frequently, thereby increasing costs and the risk of adverse effects. Drug delivery systems, such as nanoparticles, liposomes and micelles, can significantly prolong drug half-life in the body and enable targeted delivery into the joints. In this review, we comprehensively describe the pathogenesis and clinical diagnosis of rheumatoid arthritis, and summarize recent advances in targeted therapeutic strategies, particularly nano-targeting systems for rheumatoid arthritis.
{"title":"Recent advances in nano-targeting drug delivery systems for rheumatoid arthritis treatment","authors":"Hanmei Li, Rui Gou, Jiaying Liao, Yao Wang, Rui Qu, Qi Tang, Jingyao Gan, Liang Zou, Sanjun Shi","doi":"10.15212/amm-2022-0039","DOIUrl":"https://doi.org/10.15212/amm-2022-0039","url":null,"abstract":"Rheumatoid arthritis is a systemic inflammatory disease that can lead to articular cartilage destruction and periarticular bone erosion, thus ultimately compromising joint integrity and function. Anti-inflammatory drugs and biological agents are commonly used to treat rheumatoid arthritis, but they cannot selectively target inflamed joints, because of their systemic mechanisms, short half-lives and low bioavailability. Consequently, these agents must be used at high doses and delivered frequently, thereby increasing costs and the risk of adverse effects. Drug delivery systems, such as nanoparticles, liposomes and micelles, can significantly prolong drug half-life in the body and enable targeted delivery into the joints. In this review, we comprehensively describe the pathogenesis and clinical diagnosis of rheumatoid arthritis, and summarize recent advances in targeted therapeutic strategies, particularly nano-targeting systems for rheumatoid arthritis.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41844788","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}
Lydia Mukanhaire, Huijie Li, Zhengyue Fan, Liping Yang, Y. Zheng, Zhuoling Ran, Xiaoyu Zong, Lingjian Zhang, Y. Gong, Changqing Yang, Jian Gong
The objective of this study was to systematically evaluate the clinical efficacy of the complementary use of corticosteroids in the treatment of community-acquired pneumonia (CAP). We searched all relevant documents in five scientific databases from inception to June 2022 to collect clinical trials (randomized controlled trials and controlled trials) reporting on the adjunctive use of corticosteroids in CAP treatment. The primary outcome was mortality, and secondary outcomes included the time to clinical stability, therapeutic efficacy, duration of antibiotic treatment and length of hospital/ICU stay. Therapeutic efficacy was defined as the rate of achieving clinical recovery with no fever, improvement or disappearance of cough. Clinical stability was defined by improvements in laboratory values. Two researchers independently screened the literature according to the inclusion and exclusion criteria, extracted data and evaluated the quality of literature. Statistical analysis and meta-analysis of intervention measures and indicators were performed with IBM SPSS and RevMan 5.4 software. Nine randomized controlled trials comprising 2673 participants with CAP (1335 in the corticosteroid group and 1338 in the control group) were identified and included in this study. The mean cumulative corticosteroid dose and treatment duration were 298.00±287.140 mg and 5.22±1.787 days, respectively. Corticosteroid treatment was not associated with a significant decrease in mortality (RR; 95% CI, 0.96 [0.67–1.38], P=0.83). Because of the low number of included patients in our study, more studies with larger sample sizes and high-quality randomized, double-blind controlled trials are needed to confirm the results.
{"title":"Efficacy of corticosteroids as an adjunctive therapy in the treatment of community-acquired pneumonia: a systematic review and meta-analysis","authors":"Lydia Mukanhaire, Huijie Li, Zhengyue Fan, Liping Yang, Y. Zheng, Zhuoling Ran, Xiaoyu Zong, Lingjian Zhang, Y. Gong, Changqing Yang, Jian Gong","doi":"10.15212/amm-2022-0037","DOIUrl":"https://doi.org/10.15212/amm-2022-0037","url":null,"abstract":"The objective of this study was to systematically evaluate the clinical efficacy of the complementary use of corticosteroids in the treatment of community-acquired pneumonia (CAP). We searched all relevant documents in five scientific databases from inception to June 2022 to collect clinical trials (randomized controlled trials and controlled trials) reporting on the adjunctive use of corticosteroids in CAP treatment. The primary outcome was mortality, and secondary outcomes included the time to clinical stability, therapeutic efficacy, duration of antibiotic treatment and length of hospital/ICU stay. Therapeutic efficacy was defined as the rate of achieving clinical recovery with no fever, improvement or disappearance of cough. Clinical stability was defined by improvements in laboratory values. Two researchers independently screened the literature according to the inclusion and exclusion criteria, extracted data and evaluated the quality of literature. Statistical analysis and meta-analysis of intervention measures and indicators were performed with IBM SPSS and RevMan 5.4 software. Nine randomized controlled trials comprising 2673 participants with CAP (1335 in the corticosteroid group and 1338 in the control group) were identified and included in this study. The mean cumulative corticosteroid dose and treatment duration were 298.00±287.140 mg and 5.22±1.787 days, respectively. Corticosteroid treatment was not associated with a significant decrease in mortality (RR; 95% CI, 0.96 [0.67–1.38], P=0.83). Because of the low number of included patients in our study, more studies with larger sample sizes and high-quality randomized, double-blind controlled trials are needed to confirm the results.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44842843","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}
Xue Jiang, Yong-ming Zeng, Wen Zhang, Chenyuan Wang, Wei Li
Despite the advances in contraceptives, there is still a high rate of unintended pregnancies worldwide, due in large part to the lack of effective, convenient, and safe birth control methods. Compared with short-acting contraceptives, approaches that offer long-term pregnancy protection have attracted greater interest because of the reduced dosing frequency and improved patient compliance. As a novel transdermal drug delivery system, the microneedle (MN) patch has been widely used for a variety of biomedical applications, including long-acting contraception, due to unique properties, such as painless self-administration and elimination of biohazardous waste. In this review we provide a systemic review of MN patches that have been utilized for long-term contraception, including dissolvable MN patches, polymeric biodegradable MN patches, and silk fibroin-based biodegradable MN patches. The acceptability and biosafety of these contraceptive MN patches are also discussed. Finally, we give our perspectives on the future clinical translation of MN patches for long-acting contraception.
{"title":"Advances in microneedle patches for long-acting contraception","authors":"Xue Jiang, Yong-ming Zeng, Wen Zhang, Chenyuan Wang, Wei Li","doi":"10.15212/amm-2022-0042","DOIUrl":"https://doi.org/10.15212/amm-2022-0042","url":null,"abstract":"Despite the advances in contraceptives, there is still a high rate of unintended pregnancies worldwide, due in large part to the lack of effective, convenient, and safe birth control methods. Compared with short-acting contraceptives, approaches that offer long-term pregnancy protection have attracted greater interest because of the reduced dosing frequency and improved patient compliance. As a novel transdermal drug delivery system, the microneedle (MN) patch has been widely used for a variety of biomedical applications, including long-acting contraception, due to unique properties, such as painless self-administration and elimination of biohazardous waste. In this review we provide a systemic review of MN patches that have been utilized for long-term contraception, including dissolvable MN patches, polymeric biodegradable MN patches, and silk fibroin-based biodegradable MN patches. The acceptability and biosafety of these contraceptive MN patches are also discussed. Finally, we give our perspectives on the future clinical translation of MN patches for long-acting contraception.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47176864","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}
Bo Feng, Xiao Lu, Guangqin Zhang, Libo Zhao, Dong Mei
Neuroblastoma (NB) is a common solid tumor in children and infants, the formation and regression of which is closely linked to the tumor-host immune relationship. Stimulator of interferon genes (STING) agonists, particularly cyclic dinucleotide (CDN), have promising potential in NB therapy by generating innate and adaptive immune stimulation, thus leading to tumor control. CDN delivery in vivo is challenging due to the negative charge, hydrophilicity, and susceptibility to degradation by phosphodiesterase, which hinders the effectiveness of CDN. Thus, our study proposed four methods to load CDN into liposomes, using 2′,3′-cGAMP as the model drug. Lipid nanoparticles were prepared, followed by physicochemical characterization. Subsequently, cellular inhibition and immune stimulation were investigated. As a result, lipid calcium phosphate nanoparticles (LCP-NPs) possessed the highest encapsulation efficiency among the four preparation methods, with a diameter of 82.57±3.72 nm. LCP-NPs maintained size stability under refrigeration conditions at 4°C within 48 h. The surface of the liposome was positively charged. Compared to free cGAMP, LCP-NPs resulted in a slower release, enhanced cytotoxicity against tumor cells, greater activation of the cGAS-STING pathway, and increased expression of the immune factors. Taken together, these findings clearly demonstrated the effectiveness of the liposomal delivery system for cGAMP and provided a promising strategy for the treatment of NB.
{"title":"STING agonist delivery by lipid calcium phosphate nanoparticles enhances immune activation for neuroblastoma","authors":"Bo Feng, Xiao Lu, Guangqin Zhang, Libo Zhao, Dong Mei","doi":"10.15212/amm-2023-0011","DOIUrl":"https://doi.org/10.15212/amm-2023-0011","url":null,"abstract":"Neuroblastoma (NB) is a common solid tumor in children and infants, the formation and regression of which is closely linked to the tumor-host immune relationship. Stimulator of interferon genes (STING) agonists, particularly cyclic dinucleotide (CDN), have promising potential in NB therapy by generating innate and adaptive immune stimulation, thus leading to tumor control. CDN delivery in vivo is challenging due to the negative charge, hydrophilicity, and susceptibility to degradation by phosphodiesterase, which hinders the effectiveness of CDN. Thus, our study proposed four methods to load CDN into liposomes, using 2′,3′-cGAMP as the model drug. Lipid nanoparticles were prepared, followed by physicochemical characterization. Subsequently, cellular inhibition and immune stimulation were investigated. As a result, lipid calcium phosphate nanoparticles (LCP-NPs) possessed the highest encapsulation efficiency among the four preparation methods, with a diameter of 82.57±3.72 nm. LCP-NPs maintained size stability under refrigeration conditions at 4°C within 48 h. The surface of the liposome was positively charged. Compared to free cGAMP, LCP-NPs resulted in a slower release, enhanced cytotoxicity against tumor cells, greater activation of the cGAS-STING pathway, and increased expression of the immune factors. Taken together, these findings clearly demonstrated the effectiveness of the liposomal delivery system for cGAMP and provided a promising strategy for the treatment of NB.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67303295","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}
Yang Zhou, Shujing Xu, Nerea López-Carrobles, Dang Ding, Xinyong Liu, L. Menéndez-Arias, P. Zhan
Viral infections represent a major threat to human health and the global economy; however, most of the currently available antiviral drugs are not fully effective in restricting viral replication and selecting for drug-resistant variants. Targeted protein degradation technologies are promising strategies to avoid or delay the emergence of drug resistance. Among the protein degradation-based multi-specific approaches, proteolysis targeting chimera (PROTAC) is the main strategy applied in the antiviral field. In this review we will introduce the elements and mechanisms of action used by PROTAC technology, as well as the advantages of PROTACs over available antiviral drugs. We also summarize the latest progress in the application of PROTACs in antiviral research, discuss existing challenges and look into future opportunities for antiviral drug discovery.
{"title":"Recent advances in the molecular design and applications of proteolysis targeting chimera-based multi-specific antiviral modality","authors":"Yang Zhou, Shujing Xu, Nerea López-Carrobles, Dang Ding, Xinyong Liu, L. Menéndez-Arias, P. Zhan","doi":"10.15212/amm-2023-0019","DOIUrl":"https://doi.org/10.15212/amm-2023-0019","url":null,"abstract":"Viral infections represent a major threat to human health and the global economy; however, most of the currently available antiviral drugs are not fully effective in restricting viral replication and selecting for drug-resistant variants. Targeted protein degradation technologies are promising strategies to avoid or delay the emergence of drug resistance. Among the protein degradation-based multi-specific approaches, proteolysis targeting chimera (PROTAC) is the main strategy applied in the antiviral field. In this review we will introduce the elements and mechanisms of action used by PROTAC technology, as well as the advantages of PROTACs over available antiviral drugs. We also summarize the latest progress in the application of PROTACs in antiviral research, discuss existing challenges and look into future opportunities for antiviral drug discovery.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67303576","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}
Qing-Qing Xu, Wen Yang, Mei Zhong, Zhi-xiu Lin, Nora E. Gray, Yan-Fang Xian
Alzheimer’s disease (AD), an irreversible neurodegenerative disease that progressively impairs memory and cognitive judgment, severely affects the quality of life and imposes a heavy burden on the healthcare system. No cure is currently available for AD, in part because the pathogenesis of this disease has not been established. Animal models are essential for investigating AD pathogenesis and evaluating potential therapeutic strategies for AD. Some phenotypic and neuropathologic changes in AD patients can be recapitulated with genetic and pharmacologic approaches in animals. This article systematically reviews the animal models available for AD research, including transgenic, chemical- or drug-induced, and spontaneous animal models, and the characteristics of these animal models. In this review we also discuss the challenges and constraints when using AD animal models. Although no single animal model can reproduce all pathologic aspects and behavioral features in AD patients, the currently available AD models are valuable tools for deciphering the pathogenic mechanisms underlying AD and developing new anti-AD therapeutics.
{"title":"Animal models of Alzheimer’s disease: preclinical insights and challenges","authors":"Qing-Qing Xu, Wen Yang, Mei Zhong, Zhi-xiu Lin, Nora E. Gray, Yan-Fang Xian","doi":"10.15212/amm-2023-0001","DOIUrl":"https://doi.org/10.15212/amm-2023-0001","url":null,"abstract":"Alzheimer’s disease (AD), an irreversible neurodegenerative disease that progressively impairs memory and cognitive judgment, severely affects the quality of life and imposes a heavy burden on the healthcare system. No cure is currently available for AD, in part because the pathogenesis of this disease has not been established. Animal models are essential for investigating AD pathogenesis and evaluating potential therapeutic strategies for AD. Some phenotypic and neuropathologic changes in AD patients can be recapitulated with genetic and pharmacologic approaches in animals. This article systematically reviews the animal models available for AD research, including transgenic, chemical- or drug-induced, and spontaneous animal models, and the characteristics of these animal models. In this review we also discuss the challenges and constraints when using AD animal models. Although no single animal model can reproduce all pathologic aspects and behavioral features in AD patients, the currently available AD models are valuable tools for deciphering the pathogenic mechanisms underlying AD and developing new anti-AD therapeutics.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67303321","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}
Junjie Li, Shuoyi Ma, Yantao Zheng, Mengchen Qin, Hui Jia, Chang Liu, Yunjia Li, Guanghui Deng, Min Cai, Bin Liu, Lei Gao
The role of cuproptosis, a newly discovered form of programmed cell death, remains poorly understood in hepatocellular carcinoma (HCC). This study was aimed at constructing a novel cuproptosis model for analyzing the clinical features, mutation characteristics and immune profile of HCC associated with cuproptosis-related genes (CRG), and to analyze the prognostic value of CRGs in HCC. We comprehensively evaluated HCC datasets containing clinicopathological information from The Cancer Genome Atlas and GEO, on the basis of 19 CRGs. The prognostic value of the cuproptosis-related risk score was established. Our results revealed two clusters associated with cuproptosis. Cluster B exhibited pronounced isolated innate immune cell infiltration and poor prognosis, and significant differences in prognosis and immune infiltration were observed between the groups with high and low cuproptosis risk. High copper mortality risk scores were associated with an elevated tumor mutational burden (TMB) and poor prognosis. Our findings suggest that evaluating copper-death subtypes provides insights into CRGs. Moreover, the copper mortality risk score model aids in characterizing prognosis and immune infiltration independently of the TMB.
{"title":"Prognostic value and immune infiltration analyses of cuproptosis-related genes in hepatocellular carcinoma","authors":"Junjie Li, Shuoyi Ma, Yantao Zheng, Mengchen Qin, Hui Jia, Chang Liu, Yunjia Li, Guanghui Deng, Min Cai, Bin Liu, Lei Gao","doi":"10.15212/amm-2023-0035","DOIUrl":"https://doi.org/10.15212/amm-2023-0035","url":null,"abstract":"The role of cuproptosis, a newly discovered form of programmed cell death, remains poorly understood in hepatocellular carcinoma (HCC). This study was aimed at constructing a novel cuproptosis model for analyzing the clinical features, mutation characteristics and immune profile of HCC associated with cuproptosis-related genes (CRG), and to analyze the prognostic value of CRGs in HCC. We comprehensively evaluated HCC datasets containing clinicopathological information from The Cancer Genome Atlas and GEO, on the basis of 19 CRGs. The prognostic value of the cuproptosis-related risk score was established. Our results revealed two clusters associated with cuproptosis. Cluster B exhibited pronounced isolated innate immune cell infiltration and poor prognosis, and significant differences in prognosis and immune infiltration were observed between the groups with high and low cuproptosis risk. High copper mortality risk scores were associated with an elevated tumor mutational burden (TMB) and poor prognosis. Our findings suggest that evaluating copper-death subtypes provides insights into CRGs. Moreover, the copper mortality risk score model aids in characterizing prognosis and immune infiltration independently of the TMB.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134884305","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}
A significant proportion of patients who survive coronavirus disease of 2019 (COVID-19) develop a constellation of life-altering symptoms that persist long after the initial infection has resolved. This post-COVID-19 syndrome may result from the development of autoreactive IgG antibodies that cause inflammation and tissue injury. In this commentary, we suggest that efgartigimod, a drug approved for the treatment of generalized myasthenia gravis, be tested for use in patients with post-COVID-19. Efgartigimod is a humanized IgG Fc fragment containing five point mutations that significantly increase affinity for the Fc region of the neonatal crystallizable fragment receptor (FcRn). FcRn is involved in the pathogenesis of autoimmune diseases via the IgG recycling pathway because FcRN binds to autoreactive IgG antibodies and prevents the antibodies from being catabolized. Efgartigimod is a modified immunoglobulin that competitively displaces endogenous IgG from FcRn, thus increasing the level of unbound IgG, which is then catabolized and leads to decreased circulating levels of autoreactive as well as normal IgG. We suggest that efgartigimod be evaluated in a random, double-blind placebo-control trial in adults with post-COVID-19 for at least 2 months. If re-purposing this myasthenia gravis-approved drug for post - COVID-19 is successful, additional bioengineered FcRn antagonists should be tested for efficacy in patients with post-COVID-19.
{"title":"Efgartigimod, an FcRn antagonist, as a potential treatment for post COVID-19 syndrome","authors":"S. Reznik, A. Tiwari, C. Ashby","doi":"10.15212/amm-2023-0004","DOIUrl":"https://doi.org/10.15212/amm-2023-0004","url":null,"abstract":"A significant proportion of patients who survive coronavirus disease of 2019 (COVID-19) develop a constellation of life-altering symptoms that persist long after the initial infection has resolved. This post-COVID-19 syndrome may result from the development of autoreactive IgG antibodies that cause inflammation and tissue injury. In this commentary, we suggest that efgartigimod, a drug approved for the treatment of generalized myasthenia gravis, be tested for use in patients with post-COVID-19. Efgartigimod is a humanized IgG Fc fragment containing five point mutations that significantly increase affinity for the Fc region of the neonatal crystallizable fragment receptor (FcRn). FcRn is involved in the pathogenesis of autoimmune diseases via the IgG recycling pathway because FcRN binds to autoreactive IgG antibodies and prevents the antibodies from being catabolized. Efgartigimod is a modified immunoglobulin that competitively displaces endogenous IgG from FcRn, thus increasing the level of unbound IgG, which is then catabolized and leads to decreased circulating levels of autoreactive as well as normal IgG. We suggest that efgartigimod be evaluated in a random, double-blind placebo-control trial in adults with post-COVID-19 for at least 2 months. If re-purposing this myasthenia gravis-approved drug for post - COVID-19 is successful, additional bioengineered FcRn antagonists should be tested for efficacy in patients with post-COVID-19.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67303138","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}
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