Frontiers in Endocrinology
·
2022
·
IF 6.055
Linfeng Li,Baotong Zhou,Haoyang Xu,Hailin Shi,Li Gao,Bo Ge
Since 2019, coronavirus disease 2019 (COVID-19) has swept the world and become a new virus threatening the health of all mankind. The survey found that prostate cancer accounts for one in three male cancer patients infected with COVID-19. This undoubtedly makes prostate cancer patients face a more difficult situation. Prostate cancer is the second most harmful malignant tumor in men because of its insidious onset, easy metastasis, and easy development into castration-resistant prostate cancer even after treatment. Due to its high immunogenicity and a small number of specific infiltrating T cells with tumor-associated antigens in the tissue, it is difficult to obtain a good therapeutic effect with immune checkpoint blocking therapy alone. Therefore, in the current study, we developed a platform carrying Doxorubicin (DOX)-loaded black phosphate nanometer combined with photothermal therapy (PTT) and found this drug combination stimulated the immungentic cell death (ICD) process in PC-3 cells and DC maturation. More importantly, zinc ions have a good immunomodulatory function against infectious diseases, and can improve the killing ability of the nanosystem against prostate cancer cells. The introduction of Aptamer (Apt) enhances the targeting of the entire nanomedicine. We hope that this excellent combination will lead to effective treatment strategies for prostate cancer patients infected with COVID-19.
研究领域:
癌症研究
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纳米技术
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光热疗法
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免疫治疗
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病毒学
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药学
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产品关联
DOI
PubMed
高影响因子
EXPERT SYSTEMS WITH APPLICATIONS
·
2023
·
IF 8.5
Guanxing Chen,Haohuai He,Lu Zhao,Qiujie Lv,Calvin Yu-Chian Chen
The COVID-19 pandemic’s profound impact on global health and the economy underscores the need for new computational strategies to rapidly identify potential antiviral drugs against emerging and re-emerging infectious diseases. AI-based drug repurposing methods have the potential to significantly shorten the drug discovery process, rendering them a crucial and efficacious approach for screening anti-SARS-CoV-2 compounds. In this paper, we proposed GINCM-DTA, an AI-based graph isomorphism network with protein contact map representation for drug–target affinity (DTA) prediction, and presented the COVID-DTA dataset for SARS-CoV-2-specific drug repurposing. Pre-training GINCM-DTA on large-scale Davis and KIBA datasets achieved state-of-the-art performance, while fine-tuning on the COVID-DTA dataset using transfer learning resulted in a mean square error of 0.026 and concordance index of 0.967. Utilizing the fine-tuned GINCM-DTA model, we predicted DTAs for drugs against SARS-CoV-2 main targets, focusing on key conserved proteins and unmutated spike proteins for virtual screening. We integrated GINCM-DTA predictions with molecular docking simulations to identify five candidates. In vitro assays revealed Hydralazine (5.737 nM) as a potential inhibitor of ACE2 and TMPRSS2, effectively blocking SARS-CoV-2 infection. Moreover, the results highlight the potential of Hydralazine as a broad-spectrum drug candidate, demonstrating its efficacy in obstructing the binding between ACE2 and spike proteins of multiple Omicron variants, including the currently dominant strains BQ.1, BQ.1.1, XBB.1.5, and XBB.1.16. Our method offers a novel computational strategy for COVID-19 antiviral screening and prepares for potential future epidemics incited by emerging viruses.
研究领域:
人工智能
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药物发现
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计算生物学
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病毒学
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药学
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产品关联
DOI
高影响因子
PHARMACOLOGICAL RESEARCH
·
2020
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IF 5.893
Ruocong Yang,Hao Liu,Chen Bai,Yingchao Wang,Xiaohui Zhang,Rui Guo,Siying Wu,Jianxun Wang,Elaine Leung,Hang Chang,Peng Li,Tiegang Liu,Yi Wang
The Coronavirus Disease 2019 (COVID-19) pandemic has become a huge threaten to global health, which raise urgent demand of developing efficient therapeutic strategy. The aim of the present study is to dissect the chemical composition and the pharmacological mechanism of Qingfei Paidu Decoction (QFPD), a clinically used Chinese medicine for treating COVID-19 patients in China. Through comprehensive analysis by liquid chromatography coupled with high resolution mass spectrometry (MS), a total of 129 compounds of QFPD were putatively identified. We also constructed molecular networking of mass spectrometry data to classify these compounds into 14 main clusters, in which exhibited specific patterns of flavonoids (45 %), glycosides (15 %), carboxylic acids (10 %), and saponins (5 %). The target network model of QFPD, established by predicting and collecting the targets of identified compounds, indicated a pivotal role of Ma Xing Shi Gan Decoction (MXSG) in the therapeutic efficacy of QFPD. Supportively, through transcriptomic analysis of gene expression after MXSG administration in rat model of LPS-induced pneumonia, the thrombin and Toll-like receptor (TLR) signaling pathway were suggested to be essential pathways for MXSG mediated anti-inflammatory effects. Besides, changes in content of major compounds in MXSG during decoction were found by the chemical analysis. We also validate that one major compound in MXSG, i.e. glycyrrhizic acid, inhibited TLR agonists induced IL-6 production in macrophage. In conclusion, the integration of in silico and experimental results indicated that the therapeutic effects of QFPD against COVID-19 may be attributed to the anti-inflammatory effects of MXSG, which supports the rationality of the compatibility of TCM.
研究领域:
药理学
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医学
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中医药
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生物信息学
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Egyptian Journal of Internal Medicine
·
2023
·Vol. 35
·期 1
·1-9
·
IF 0
Muslim Shahnawaz,Mustafa Gulam,Nasrin Nasrin,Firdaus Aaisha,Singh Shambhu Kumar
SARS-CoV-2, the causative agent of COVID-19, claimed multiple lives in a very short span of time. Seeing the urgency of situation, vaccines were developed in hitherto unseen time frame. Vaccines definitely passed the test of safety and efficacy in clinical trials, but post mass vaccination data revealed cases of fatal adverse conditions in the temporal association of vaccination. The temporal association does not guarantee that the fatality is due to vaccination, but at the same time, it does create a concern. To overcome this concern and improve the safety of vaccination, we reviewed literature and collected data of 15 studies comprising of total 22 cases of fatal adverse condition/death in the temporal association of COVID-19 vaccination. Analysis of these data shows that many persons (40.90%) who succumbed were previously healthy individuals. All those who died developed symptoms or were admitted to hospital within a period of 3 weeks after vaccination. 86.36% cases of death took place within a period of 3 weeks after vaccination/presentation/admission/intervention. Complications which lead to death were CVST, thrombocytopenia/thrombosis /VITT, DIC and haemorrhage in 81.18% of cases. 81.81% cases of death were noted in the temporal association with ChAdOx1 nCoV-19 vaccine. 68.18% persons developed symptoms after first dose. Death was more common in females (59.09%), and the most commonly affected age group was 20 to 60 years (86.36%). Knowledge of fatal adverse conditions in the temporal association of vaccination will help to tackle these situations well and improve the safety of vaccination drive further.
研究领域:
免疫学
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流行病学
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公共卫生
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药理学
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转化医学
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DOI
BMC Medical Informatics and Decision Making
·
2021
·Vol. 21
·期 9
·271
·
IF 2.796
Wu Huanhuan,Zhong Yichen,Tian Yingjie,Jiang Shan,Luo Lingyun
Background 2019-nCoV has been spreading around the world and becoming a global concern. To prevent further widespread of 2019-nCoV, confirmed and suspected cases of COVID-19 infection are suggested to be kept in quarantine. However, the diagnose of COVID-19 infection is quite time-consuming and labor-intensive. To alleviate the burden on the medical staff, we have done some research on the intelligent diagnosis of COVID-19. Methods In this paper, we constructed a COVID-19 Diagnosis Ontology (CDO) by utilizing Protégé, which includes the basic knowledge graph of COVID-19 as well as diagnostic rules translated from Chinese government documents. Besides, SWRL rules were added into the ontology to infer intimate relationships between people, thus facilitating the efficient diagnosis of the suspected cases of COVID-19 infection. We downloaded real-case data and extracted patients’ syndromes from the descriptive text, so as to verify the accuracy of this experiment. Results After importing those real instances into Protégé, we demonstrated that the COVID-19 Diagnosis Ontology showed good performances to diagnose cases of COVID-19 infection automatically. Conclusions In conclusion, the COVID-19 Diagnosis Ontology will not only significantly reduce the manual input in the diagnosis process of COVID-19, but also uncover hidden cases and help prevent the widespread of this epidemic.
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DOI
高影响因子
International Insolvency Review
·
2021
·Vol. 30
·期 3
·329-343
·
IF 0.848
Daniel A. Austin,Yu Huan
Business bankruptcy in China is governed by the Enterprise Bankruptcy Law (EBL), a national insolvency code enacted in 2007. The EBL contains provisions for business liquidation, reorganization, and compromise of debt. Although adjustment of debt through bankruptcy is far less common in China than in western nations, Chinese courts have established a body of bankruptcy procedures and judicial interpretations that give insolvency in China a measure of predictability and effectiveness. Notwithstanding the EBL provisions, soon after the onset of the pandemic, PRC courts began to adopt ad-hoc rules and guidelines in bankruptcy cases for businesses whose financial woes were caused or exacerbated by coronavirus, or for enterprises that produced medical equipment and supplies to help prevent and control the virus. This paper examines these court measures, explores their political and judicial context, and demonstrates how they produced bankruptcy outcomes that were often significantly different than what would have resulted if the EBL had been applied based on pre-COVID-19 EBL practices.
研究领域:
法学
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经济法学
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破产法
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司法制度
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公共政策
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DOI
高影响因子
Scientific Reports
·
2021
·Vol. 11
·期 1
·1-7
·
IF 4.38
Xiong Xisheng,Wang Kun,Tang Tao,Fang Jinzhi,Chen Yijun
Hydroxychloroquine (2-[[4-[(7-Chloroquinolin-4-yl) amino]pentyl](ethyl) amino]-ethanol, HCQ), an effective anti-malarial drug, has been tested in the clinics for potential treatment of severe coronavirus disease 2019 (COVID-19). Despite the controversy around the clinical benefits of HCQ, the existence of a chiral center in the molecule to possess two optical isomers suggests that there might be an enantiomeric difference on the treatment of COVID-19. Due to their poor resolution and the inability of quantification by previously reported methods for the analysis of HCQ enantiomers, it is necessary to develop an analytical method to achieve baseline separation for quantitative and accurate determination of the enantiomeric purity in order to compare the efficacy and toxicity profiles of different enantiomers. In this study, we developed and validated an accurate and reproducible normal phase chiral high-performance liquid chromatography (HPLC) method for the analysis of two enantiomers of HCQ, and the method was further evaluated with biological samples. With this newly developed method, the relative standard deviations of all analytes were lower than 5%, and the limits of quantification were 0.27 μg/ml, 0.34 μg/ml and 0.20 μg/ml for racemate, R- and S-enantiomer, respectively. The present method provides an essential analytical tool for preclinical and clinical evaluation of HCQ enantiomers for potential treatment of COVID-19.
研究领域:
药物化学
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分析化学
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传染病学
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2021
·
IF 7.46
Yaqin Zhang,Minyan Chen,Chengrong Liu,Jiaqi Chen,Xinyi Luo,Yingying Xue,Qiming Liang,Li Zhou,Yu Tao,Mingqiang Li,Di Wang,Jianhua Zhou,Jiasi Wang
The outbreak of corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a global pandemic. The high infectivity of SARS-CoV-2 highlights the need for sensitive, rapid and on-site diagnostic assays of SARS-CoV-2 with high-throughput testing capability for large-scale population screening. The current detection methods in clinical application need to operate in centralized labs. Though some on-site detection methods have been developed, few tests could be performed for high-throughput analysis. We here developed a gold nanoparticle-based visual assay that combines with CRISPR/Cas12a-assisted RT-LAMP, which is called C as12a-assisted RT- LA MP/AuN P (CLAP) assay for rapid and sensitive detection of SARS-CoV-2. In optimal condition, we could detect down to 4 copies/μL of SARS-CoV-2 RNA in 40 min. by naked eye. The sequence-specific recognition character of CRISPR/Cas12a enables CLAP a superior specificity. More importantly, the CLAP is easy for operation that can be extended to high-throughput test by using a common microplate reader. The CLAP assay holds a great potential to be applied in airports, railway stations, or low-resource settings for screening of suspected people. To the best of our knowledge, this is the first AuNP-based colorimetric assay coupled with Cas12 and RT-LAMP for on-site diagnosis of COVID-19. We expect CLAP assay will improve the current COVID-19 screening efforts, and make contribution for control and mitigation of the pandemic.
研究领域:
分子生物学
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病毒学
·
诊断检测
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纳米技术
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公共卫生
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Public Health
·
2026
·
IF 4.1
Yongzhong Jiang,Xiang Cheng,Ahmet Tanhan,Vincent T. Francisco,Ihsan Cagatay Ulus,Melissa Hauber-Ozer,Ruixue Zou
This study investigates the primary facilitators of and barriers to mental health among Chinese participants during the COVID-19 pandemic. We collected the participants’ experiences using the Online Photovoice (OPV) method and analyzed the data through Online Interpretative Phenomenological Analysis (OIPA) to identify key facilitators and barriers. The results of the study revealed 12 major facilitator themes, including social support (21.58%, n = 41), socialization (15.26%, n = 29), and scenery (14.21%, n = 27). Conversely, eight major barrier themes emerged, including restricted daily life (34.71%, n = 59), the economy (32.94%, n = 56), and epidemic prevention policy (27.12%, n = 41). We discussed the findings and provided suggestions for researchers, mental health providers, key authorities, and educators. Our findings provide important implications for intervening in the mental health of individuals in response to the negative impact of the COVID-19 pandemic. As the researchers and the partners helped us with the study, we keep sharing the results with key authorities and at academic platforms.
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DOI
高影响因子
ACS Nano
·
2021
·
IF 15.881
Yue Yin,Wen Su,Jie Zhang,Wenping Huang,Xiaoyang Li,Haixia Ma,Mixiao Tan,Haohao Song,Guoliang Cao,Shengji Yu,Di Yu,Ji Hoon Jeong,Xiao Zhao,Hui Li,Guangjun Nie,Hai Wang
The successful control of coronavirus disease 2019 (COVID-19) pandemic is not only relying on the development of vaccines, but also depending on the storage, transportation, and administration of vaccines. Ideally, nucleic acid vaccine should be directly delivered to proper immune cells or tissue (such as lymph nodes). However, current developed vaccines are normally treated through intramuscular injection, where immune cells do not normally reside. Meanwhile, current nucleic acid vaccines must be stored in a frozen state that may hinder their application in developing countries. Here, we report a separable microneedle (SMN) patch to deliver polymer encapsulated spike (or nucleocapsid) protein encoding DNA vaccines and immune adjuvant for efficient immunization. Compared with intramuscular injection, SMN patch can deliver nanovaccines into intradermal for inducing potent and durable adaptive immunity. IFN-γ+CD4/8+ and IL-2+CD4/8+ T cells or virus specific IgG are significantly increased after vaccination. Moreover, in vivo results show the SMN patches can be stored at room temperature for at least 30 days without decreases in immune responses. These features of nanovaccines-laden SMN patch are important for developing advanced COVID-19 vaccines with global accessibility.
研究领域:
生物医学工程
·
疫苗开发
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免疫学
✓ 已验证
DOI
PubMed
高影响因子
Current Drug Safety
·
2024
·Vol. 20
·期 1
·33-47
·
IF 1.1
Viswarupachari Tanguturi Yella,Sumit Pareek,Bhumika Meena,K.S.B.S. Krishna Sasanka,Pugazhenthan Thangaraju,Sree Sudha T Y
Aims & ObjectivesThe objective of this study was to conduct a systematic review of research pertaining to the COVID-19 vaccine and its association with neurological complications.MethodsWe performed a comprehensive search of the literature using Google Scholar, PubMed, and NCBI databases from December 2021 to December 2022. For Google Scholar, PubMed, and NCBI databases we used the following key search terms: “neurological adverse effects”, “COVID-19 vaccination”, “SARS-CoV-2”, CNS complications, and CNS adverse effects. Two reviewer authors individually searched and assessed the titles and abstracts of all articles. The third reviewer resolved the disagreement between them. Data were documented regarding title, study location, type of study, type of COVID-19 vaccine, type of neurological complications/adverse effects, and sample size.ResultsFrom our findings, it is confirmed that these neurological complications like Guillain-Barre syndrome (23.6%), Neuromyelitis Optica spectrum disorder (5.5%), Neuropathy (6.9%), Transverse Myelitis (8.3%) and Acute disseminated Encephalomyelitis (4.1%) are majorly affected in most of the people. The increase in risks associated with SARS-CoV-2 infection far outweighs any previously reported associations with vaccination.ConclusionWe found no safety signal was observed between COVID-19 vaccines and the immune-mediated neurological events. Before assuming a causal relationship, the side effects of the COVID-19 vaccine should first be carefully examined to rule out known associated factors. Symptom onset was within two weeks of vaccination in the majority of cases; as such, this seems to be a high-risk period warranting vigilance.
研究领域:
医学
·
免疫学
·
神经科学
✓ 已验证
DOI
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 19
·4713
·
IF 4.2
Wei He,Qi Geng,Guiying Ji,Ji Li,Dan Wang,Yucai He,Qiuheng Jin,Jianren Ye
The remarkable efficacy of COVID-19 vaccines has established mRNA as a highly promising biomedical technology. However, the adequate application of mRNA therapeutics necessitates additional measures to mitigate the inherent immunogenicity, which is predominantly caused by dsRNA. As a byproduct of the in vitro transcription of mRNA, dsRNA was reported to be originated through several distinct mechanisms, including the extension of 3′ loop-back hairpins, the extension of hybridized abortive transcripts, and promoter-independent transcription. The intricate mechanisms involved pose a dilemma as the reduction in dsRNA results in a concomitant decrease in other critical quality attributes of mRNA. Here, we demonstrate that the promoter binding motifs of T7 RNA polymerase directly impact the production of promoter-independent transcription-based dsRNA. Specifically, the G753A mutation significantly reduces the formation of dsRNA byproducts, which can further combine with modified nucleotides to enhance the effectiveness of dsRNA mitigation and with previously reported high-integrity mutation K389A to minimize side effects. Accordingly, the present study reports a cost-effective approach to synthesize high-purity, less immunostimulatory mRNA by using an engineered T7 RNA polymerase mutant.
研究领域:
分子生物学
·
生物技术
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）