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1.
Bioorg Med Chem ; 48: 116398, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34547714

RESUMO

Despite the success of imatinib in CML therapy through Bcr-Abl inhibition, acquired drug resistance occurs over time in patients. In particular, the resistance caused by T315I mutation remains a challenge in clinic. Herein, we embarked on a structural optimization campaign aiming at discovery of novel Bcr-Abl inhibitors toward T315I mutant based on previously reported dibenzoylpiperazin derivatives. We proposed that incorporation of flexible linker could achieve potent inhibition of Bcr-AblT315I by avoiding steric clash with bulky sidechain of Ile315. A library of 28 compounds with amino acids as linker has been developed and evaluated. Among them, compound AA2 displayed the most potent activity against Bcr-AblWT and Bcr-AblT315I, as well as toward Bcr-Abl driven K562 and K562R cells. Further investigations indicated that AA2 could induce apoptosis of K562 cells and down regulate phosphorylation of Bcr-Abl. In summary, the compounds with amino acid as novel flexible linker exhibited certain antitumor activities, providing valuable hints for the discovery of novel Bcr-Abl inhibitors to overcome T315I mutant resistance, and AA2 could be considered as a candidate for further optimization.

2.
Top Curr Chem (Cham) ; 379(6): 39, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34590223

RESUMO

Bioorthogonal reactions are rapid, specific and high yield reactions that can be performed in in vivo microenvironments or simulated microenvironments. At present, the main biorthogonal reactions include Staudinger ligation, copper-catalyzed azide alkyne cycloaddition, strain-promoted [3 + 2] reaction, tetrazine ligation, metal-catalyzed coupling reaction and photo-induced biorthogonal reactions. To date, many reviews have reported that bioorthogonal reactions have been used widely as a powerful tool in the field of life sciences, such as in target recognition, drug discovery, drug activation, omics research, visualization of life processes or exogenous bacterial infection processes, signal transduction pathway research, chemical reaction dynamics analysis, disease diagnosis and treatment. In contrast, to date, few studies have investigated the application of bioorthogonal reactions in the analysis of biomacromolecules in vivo. Therefore, the application of bioorthogonal reactions in the analysis of proteins, nucleic acids, metabolites, enzyme activities and other endogenous molecules, and the determination of disease-related targets is reviewed. In addition, this review discusses the future development opportunities and challenges of biorthogonal reactions. This review presents an overview of recent advances for application in biomolecular analysis and disease diagnosis, with a focus on proteins, metabolites and RNA detection.


Assuntos
Neoplasias/diagnóstico , Proteínas/análise , RNA/análise , Biomarcadores/análise , Reação de Cicloadição , Fezes/química , Corantes Fluorescentes/química , Fumaratos/análise , Humanos , Proteínas/química , Proteínas/metabolismo , RNA/química
3.
Anal Chem ; 93(38): 12848-12853, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34520178

RESUMO

Quantum dot (QD)-based digital immunoassays play an important role in ultrasensitive biomarker detection. However, the requirement of an objective with a high numerical aperture (NA) limits the application of this immunoassay. Here, high-quality imaging of massive single-QDs was achieved by the combination of an air objective (20×/0.4 NA) and liquid-immersed microspheres (150 µm, n = 2.2). The signal-to-noise ratio was comparable to that of a 100×/1.4 NA oil objective. Digital analysis of prostate-specific antigen (PSA) was performed within the dynamic range of 0-50 ng/mL and a limit of detection of 0.17 ng/mL. The measured serum data from the PSA were close to the values provided by a hospital. Using a low-magnification and low-NA objective may reduce the barrier of microscopy miniaturization and is beneficial to popularize biomolecular digital analysis.


Assuntos
Pontos Quânticos , Humanos , Imunoensaio , Masculino , Microesferas , Antígeno Prostático Específico , Soro
4.
Curr Top Med Chem ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503405

RESUMO

Cancer is the second leading cause of human death after cardiovascular disease, and the most used drugs in clinics are cytotoxic agents. However, these drugs have some inherent disadvantages, such as the risk of toxicity, low selectivity, poor solubility, and so on. To overcome these shortcomings, a variety of drug delivery strategies based on prodrugs have been developed. The application of drug delivery systems can optimize ADME properties of cytotoxic agents and improve their selectivity at the target, thereby greatly enhancing the anticancer effect in clinics. At present, it has become mainstream in drug design. This review systematically summarized the studies of prodrug-based drug delivery systems over the past five to ten years, according to four aspects, solubility, controlled release, in situ concentration, and targeting.

5.
Drug Dev Res ; 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34424555

RESUMO

Herein, two novel multifunctional releasable photoaffinity linkers were developed for effective and transient tracking interacting proteins with the overall objective of understanding their in vivo biological functions in real-time. These linkers could be used for the chemical modification of protein under moderate experimental conditions to form protein photoaffinity probes. These probes incorporated with both photoaffinity labels and tag-transfer, enable photo-crosslinking of bait proteins along with the release of unrelated groups. These photoaffinity linkers can be utilized to construct probes for disease markers, which could enable rapid diagnosis in a clinical setting at minimal interference with normal physiology.

6.
Drug Discov Today ; 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34332098

RESUMO

A major problem associated with cancer treatment is resistance-prone chemotherapeutic drugs. An increasing number of studies have documented that the occurrence of resistance tends to be associated with abnormal blood vessels. In 2001, Jain proposed the vascular normalization theory, which was recently applied to the drug-resistant treatment of tumors in the clinic. Through the intervention of angiogenesis inhibitors, remodeling the structure and function of abnormal vessels can maximize the efficacy of chemotherapeutic drugs. In this review, we systematically describe the occurrence and progress of tumor angiogenesis, as well as the pathological characteristics of tumor blood vessels. Moreover, druggable targets for vascular normalization and the development of related inhibitors are also outlined.

7.
Acta Pharmacol Sin ; 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34267343

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can induce acute inflammatory response like acute lung inflammation (ALI) or acute respiratory distress syndrome, leading to severe progression and mortality. Therapeutics for treatment of SARS-CoV-2-triggered respiratory inflammation are urgent to be discovered. Our previous study shows that Salvianolic acid C potently inhibits SARS-CoV-2 infection. In this study, we investigated the antiviral effects of a Salvia miltiorrhiza compound, Danshensu, in vitro and in vivo, including the mechanism of S protein-mediated virus attachment and entry into target cells. In authentic and pseudo-typed virus assays in vitro, Danshensu displayed a potent antiviral activity against SARS-CoV-2 with EC50 of 0.97 µM, and potently inhibited the entry of SARS-CoV-2 S protein-pseudo-typed virus (SARS-CoV-2 S) into ACE2-overexpressed HEK-293T cells (IC50 = 0.31 µM) and Vero-E6 cell (IC50 = 4.97 µM). Mice received SARS-CoV-2 S via trachea to induce ALI, while the VSV-G treated mice served as controls. The mice were administered Danshensu (25, 50, 100 mg/kg, i.v., once) or Danshensu (25, 50, 100 mg·kg-1·d-1, oral administration, for 7 days) before SARS-CoV-2 S infection. We showed that SARS-CoV-2 S infection induced severe inflammatory cell infiltration, severely damaged lung tissue structure, highly expressed levels of inflammatory cytokines, and activated TLR4 and hyperphosphorylation of the NF-κB p65; the high expression of angiotensinogen (AGT) and low expression of ACE2 at the mRNA level in the lung tissue were also observed. Both oral and intravenous pretreatment with Danshensu dose-dependently alleviated the pathological alterations in mice infected with SARS-CoV-2 S. This study not only establishes a mouse model of pseudo-typed SARS-CoV-2 (SARS-CoV-2 S) induced ALI, but also demonstrates that Danshensu is a potential treatment for COVID-19 patients to inhibit the lung inflammatory response.

8.
Cell Res ; 31(8): 847-860, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34112954

RESUMO

Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.


Assuntos
Antivirais/metabolismo , COVID-19/patologia , Proteínas do Envelope de Coronavírus/metabolismo , Síndrome do Desconforto Respiratório/etiologia , SARS-CoV-2/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Animais , Antivirais/química , Antivirais/uso terapêutico , Apoptose , COVID-19/complicações , COVID-19/tratamento farmacológico , COVID-19/virologia , Proteínas do Envelope de Coronavírus/antagonistas & inibidores , Proteínas do Envelope de Coronavírus/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Meia-Vida , Humanos , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutagênese Sítio-Dirigida , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/patogenicidade , Baço/metabolismo , Baço/patologia , Carga Viral , Virulência
9.
J Sep Sci ; 44(16): 3061-3069, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34110096

RESUMO

Carthami flos, commonly known as Honghua in China, is the dried floret of safflower and widely acknowledged as a blood stasis promoting herb. The study aimed at investigating the relationship between thrombin and carthami flos through a high-performance thrombin affinity chromatography combined with a high-performance liquid chromatography-tandem mass spectrometry system. First, thrombin was immobilized on the glutaraldehyde-modified amino silica gel to prepare the thrombin affinity stationary phase, which was packed into a small column (1.0 × 2.0 mm, id) for recognizing the anticoagulant active components of carthami flos. The target component was enriched and analyzed by the high-performance liquid chromatography-tandem mass spectrometry system. Finally, hydroxysafflor yellow A was screened out and identified as the active component. The anticoagulant effects of hydroxysafflor yellow A were analyzed by anticoagulant experiments in vitro, and the interaction of hydroxysafflor yellow A with thrombin was investigated by the molecular docking method. The results proved that hydroxysafflor yellow A (30 µg/mL, 0.05 mM) and carthami flos extract (30 µg/mL) could prolong activated partial thrombin time and thrombin time by 50 and 11%, respectively. Moreover, hydroxysafflor yellow A exhibits a good hydrogen bond field and stereo field matching with thrombin. Overall, it was concluded that hydroxysafflor yellow A might exert an anticoagulation effect by interacting with thrombin and thus could be potential anticoagulant drugs for the prevention and treatment of venous thrombosis.

10.
Br J Nutr ; : 1-8, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34176541

RESUMO

Sarcopenic obesity is regarded as a risk factor for the progression and development of non-alcoholic fatty liver disease (NAFLD). Since male sex is a risk factor for NAFLD and skeletal muscle mass markedly varies between the sexes, we examined whether sex influences the association between appendicular skeletal muscle mass to visceral fat area ratio (SVR), that is, an index of skeletal muscle mass combined with abdominal obesity, and the histological severity of NAFLD. The SVR was measured by bioelectrical impedance in a cohort of 613 (M/F = 443/170) Chinese middle-aged individuals with biopsy-proven NAFLD. Multivariable logistic regression and subgroup analyses were used to test the association between SVR and the severity of NAFLD (i.e. non-alcoholic steatohepatitis (NASH) or NASH with the presence of any stage of liver fibrosis). NASH was identified by a NAFLD activity score ≥5, with a minimum score of 1 for each of its categories. The presence of fibrosis was classified as having a histological stage ≥1. The SVR was inversely associated with NASH in men (adjusted OR 0·62; 95 % CI 0·42, 0·92, P = 0·017 for NASH, adjusted OR 0·65; 95 % CI 0·43, 0·99, P = 0·043 for NASH with the presence of fibrosis), but not in women (1·47 (95 % CI 0·76, 2·83), P = 0·25 for NASH, and 1·45 (95 % CI 0·74, 2·83), P = 0·28 for NASH with the presence of fibrosis). There was a significant interaction for sex and SVR (Pinteraction = 0·017 for NASH and Pinteraction = 0·033 for NASH with the presence of fibrosis). Our findings show that lower skeletal muscle mass combined with abdominal obesity is strongly associated with the presence of NASH only in men.

11.
J Phys Chem Lett ; : 4799-4804, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-33998813

RESUMO

The Li-air battery is expected to become the next generation of the energy storage system because of its high theoretical energy density of 3500 Wh/kg (based on Li2O2 formation at the cathode). CO2 (∼300 ppm) in the air is regarded as an impurity for cathode reactions, because it can lead to the formation of Li2CO3, which increases the overcharge potentials, decreases energy efficiency, and gives rise to the serious decomposition of battery components. However, the impact of a low concentration of CO2 (<1000 ppm) on cell performance has not been addressed. In this work, we quantitatively characterized and analyzed the impact of a low concentration of CO2 on the electrochemical performance of Li-air batteries to investigate the tolerance of Li-air batteries to CO2. The discharge capacities and cyclability of the batteries with CO2 below 100 ppm are similar to those without CO2. The batteries with 0, 50, and 100 ppm of CO2 delivered 85, 88, and 83 cycles, respectively. At the same time, the critical byproduct Li2CO3 was quantified, and its effect on batteries is analyzed by in situ electrochemical impedance spectroscopy (EIS) with a distribution of relaxation time (DRT) calculation. This study promises a theoretical basis for developing CO2 removal materials and devices for Li-air batteries in the future.

12.
Oncol Rep ; 46(1)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34036393

RESUMO

Chronic myeloid leukemia (CML) accounts for approximately 15% of new adult leukemia cases. The fusion gene BCR­ABL is an important biological basis and target for CML. In the present study, a novel compound, ND­09, was developed and its inhibitory effect and mechanism of action on CML growth were evaluated using RT­PCR and western blot analysis. The results showed that ND­09 demonstrated a high level of inhibitory action toward CML cells overexpressing BCR­ABL and induced K562 cell apoptosis through the mitochondrial pathway. Notably, combined ND­09 and BCR­ABL siRNA treatment could better inhibit cell proliferation and induce apoptosis in K562 cells. Furthermore, this growth effect of BCR­ABL siRNA could be fully rescued by transfection with BCR­ABL. ND­09 exhibited a good fit within BCR­ABL and occupied its ATP­binding pocket, thus altering BCR­ABL kinase activity. Therefore, ND­09 downregulated the phosphorylation of BCR­ABL and ABL, ultimately inhibiting the downstream signaling pathways in K562 cells. These findings suggest that ND­09 induces growth arrest in CML cells by targeting BCR­ABL.

13.
Medicine (Baltimore) ; 100(16): e25524, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33879692

RESUMO

RATIONALE: Acutefatty liver of pregnancy (AFLP) is a potentially fatal obstetric emergency characterized by acute hepatic failure secondary to fatty infiltration. The resultant effects include coagulopathy, electrolyte abnormalities, and multisystem organ dysfunction. Pancreatitis typically develops after the onset of renal and hepatic dysfunction. Pancreatitis has been suggested as a poor prognostic indicator because it is associated with more adverse outcomes. PATIENT CONCERNS: A 29-year-old Chinese woman at 34.7 weeks pregnancy was admitted to hospital due to paroxysmal hypogastric pain and massive colporrhagia for 1 day. DIAGNOSIS: Laboratory tests revealed hepatic and renal impairment, coagulopathy. Thoracoabdominal computed tomography (CT) scanning showed pleural and peritoneal effusion, fatty liver, and pancreatitis. She was diagnosed with AFLP, severe acute pancreatitis (SAP), multiple organ dysfunction syndrome (MODS), and intrauterine fetal death. INTERVENTIONS: The patient was treated with blood component transfusions, plasma exchange combined with renal replacement therapy, antibiotic de-escalation, gastric and pancreatic secretion inhibitor, and enteral nutrition. OUTCOMES: After successful management, the patient was discharged without any complications on day 35 of admission. At 10 months follow-up, thoracoabdominal enhanced CT revealed was normal and laboratory tests revealed normal liver and kidney function. LESSONS: Once AFLP is highly suspected or confirmed, the pregnancy should be terminated in time and active symptomatic management should be given.


Assuntos
Fígado Gorduroso/diagnóstico , Falência Hepática Aguda/diagnóstico , Insuficiência de Múltiplos Órgãos/diagnóstico , Pancreatite/diagnóstico , Complicações na Gravidez/diagnóstico , Natimorto , Adulto , Fígado Gorduroso/complicações , Feminino , Humanos , Fígado/diagnóstico por imagem , Falência Hepática Aguda/etiologia , Testes de Função Hepática , Insuficiência de Múltiplos Órgãos/etiologia , Pâncreas/diagnóstico por imagem , Pancreatite/etiologia , Gravidez , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
14.
J Hepatobiliary Pancreat Sci ; 28(7): 593-603, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33908180

RESUMO

BACKGROUND: The presence of significant liver fibrosis is a key determinant of long-term prognosis in non-alcoholic fatty liver disease (NAFLD). We aimed to develop a novel machine learning algorithm (MLA) to predict fibrosis severity in NAFLD and compared it with the most widely used non-invasive fibrosis biomarkers. METHODS: We used a cohort of 553 adults with biopsy-proven NAFLD, who were randomly divided into a training cohort (n = 278) for the development of both logistic regression model (LRM) and MLA, and a validation cohort (n = 275). Significant fibrosis was defined as fibrosis stage F ≥ 2. MLA and LRM were derived from variables that were selected using a least absolute shrinkage and selection operator (LASSO) logistic regression algorithm. RESULTS: In the training cohort, the variables selected by LASSO algorithm were body mass index, pro-collagen type III, collagen type IV, aspartate aminotransferase and albumin-to-globulin ratio. The diagnostic accuracy of MLA showed the highest values of area under the receiver operator characteristic curve (AUROC: 0.902, 95% CI 0.869-0.904) for identifying fibrosis F ≥ 2. The LRM AUROC was 0.764, 95% CI 0.710-0.816 and significantly better than the AST-to-Platelet ratio (AUROC 0.684, 95% CI 0.605-0.762), FIB-4 score (AUROC 0.594, 95% CI 0.503-0.685) and NAFLD Fibrosis Score (AUROC 0.557, 95% CI 0.470-0.644). In the validation cohort, MLA also showed the highest AUROC (0.893, 95% CI 0.864-0.901). The diagnostic accuracy of MLA outperformed that of LRM in all subgroups considered. CONCLUSIONS: Our newly developed MLA algorithm has excellent diagnostic performance for predicting fibrosis F ≥ 2 in patients with biopsy-confirmed NAFLD.

15.
Protein Cell ; 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33864621

RESUMO

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (Mpro), PLpro is responsible for processing the viral replicase polyprotein into functional units. Therefore, it is an attractive target for antiviral drug development. Here we discovered four compounds, YM155, cryptotanshinone, tanshinone I and GRL0617 that inhibit SARS-CoV-2 PLpro with IC50 values ranging from 1.39 to 5.63 µmol/L. These compounds also exhibit strong antiviral activities in cell-based assays. YM155, an anticancer drug candidate in clinical trials, has the most potent antiviral activity with an EC50 value of 170 nmol/L. In addition, we have determined the crystal structures of this enzyme and its complex with YM155, revealing a unique binding mode. YM155 simultaneously targets three "hot" spots on PLpro, including the substrate-binding pocket, the interferon stimulating gene product 15 (ISG15) binding site and zinc finger motif. Our results demonstrate the efficacy of this screening and repurposing strategy, which has led to the discovery of new drug leads with clinical potential for COVID-19 treatments.

16.
Curr Med Chem ; 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33820512

RESUMO

Hydrogel is a hydrophilic but water-soluble polymer system with a three-dimensional network structure. Hydrogel can absorb large amounts of water and maintain its shape and remain soft. The high-moisturizing properties, good biocompatibility and controlled biodegradability of hydrogels have allowed them to be widely used in wound dressing, tissue engineering, controlled drug delivery systems and other fields. This article reviews the most widely used antibacterial gel dressings for wound healing in recent years and focuses on the application of an environmentally responsive intelligent hydrogel delivery system. Finally, the development prospects and challenges of hydrogel wound dressings are forecasted.

17.
Adv Ther (Weinh) ; : 2000224, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33786369

RESUMO

SARS-CoV-2 caused the emerging epidemic of coronavirus disease in 2019 (COVID-19). To date, there are more than 82.9 million confirmed cases worldwide, there is no clinically effective drug against SARS-CoV-2 infection. The conserved properties of the membrane fusion domain of the spike (S) protein across SARS-CoV-2 make it a promising target to develop pan-CoV therapeutics. Herein, two clinically approved drugs, Itraconazole (ITZ) and Estradiol benzoate (EB), are found to inhibit viral entry by targeting the six-helix (6-HB) fusion core of SARS-CoV-2 S protein. Further studies shed light on the mechanism that ITZ and EB can interact with the heptad repeat 1 (HR1) region of the spike protein, to present anti-SARS-CoV-2 infections in vitro, indicating they are novel potential therapeutic remedies for COVID-19 treatment. Furthermore, ITZ shows broad-spectrum activity targeting 6-HB in the S2 subunit of SARS-CoV and MERS-CoV S protein, inspiring that ITZ have the potential for development as a pan-coronavirus fusion inhibitor.

18.
Anal Chem ; 93(6): 3089-3095, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33539073

RESUMO

Digital multiplexed homogeneous immunoassay is supposed to have the advantages of high sensitivity, high analytical throughput, small sampling errors, and low consumption. We present a spectral imaging-based multiplex, homogenous immunoassay by counting sandwich-structured immunocomplexes in the form of quantum dot (QD) aggregates. As a proof of concept, the method was utilized to detect two tumor biomarkers: carcino-embryonic antigen (CEA) and α-fetoprotein (AFP). The immunocomplex induced by CEA contained QD 655 and QD 585 and were recognized by the spectral pattern of dual-color QD aggregates under a transmission-grating-based spectral imaging microscope. Immunocomplexes induced by AFP were labeled with the QD 585 aggregate and were identified by the spectral blue-shift pattern of same-color QD aggregates. Limits of detection for AFP and CEA were calculated to be 0.02 and 0.10 pM at a signal-to-noise ratio of 3, respectively. Further successful quantification of the model proteins in human plasma demonstrated the accuracy and reliability of our approach.


Assuntos
Pontos Quânticos , Biomarcadores Tumorais , Antígeno Carcinoembrionário , Humanos , Imunoensaio , Testes Imunológicos , Reprodutibilidade dos Testes , alfa-Fetoproteínas
19.
Top Curr Chem (Cham) ; 379(2): 10, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33544237

RESUMO

Fluorescence imaging is an important method in the field of biomedicine. Fluorescence imaging is nondestructive, has high efficiency and sensitivity, high resolution and allows real-time dynamic monitoring of living cells. However, it also has some disadvantages, such as high background signals and low selectivity. Bioorthogonal reactions, with the advantages of being both nondestructive and effective, are used to trace and analyze biological interactions in vivo. This review focuses on recent progress in understanding the mechanism of action of fluorescence probes.


Assuntos
Corantes Fluorescentes/metabolismo , Imagem Óptica , Corantes Fluorescentes/química , Estrutura Molecular
20.
Cell Rep ; 34(7): 108761, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33567255

RESUMO

Coronavirus disease 2019 (COVID-19) is a current global health threat caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging evidence indicates that SARS-CoV-2 elicits a dysregulated immune response and a delayed interferon (IFN) expression in patients, which contribute largely to the viral pathogenesis and development of COVID-19. However, underlying mechanisms remain to be elucidated. Here, we report the activation and repression of the innate immune response by SARS-CoV-2. We show that SARS-CoV-2 RNA activates the RIG-I-MAVS-dependent IFN signaling pathway. We further uncover that ORF9b immediately accumulates and antagonizes the antiviral type I IFN response during SARS-CoV-2 infection on primary human pulmonary alveolar epithelial cells. ORF9b targets the nuclear factor κB (NF-κB) essential modulator NEMO and interrupts its K63-linked polyubiquitination upon viral stimulation, thereby inhibiting the canonical IκB kinase alpha (IKKα)/ß/γ-NF-κB signaling and subsequent IFN production. Our findings thus unveil the innate immunosuppression by ORF9b and provide insights into the host-virus interplay during the early stage of SARS-CoV-2 infection.


Assuntos
Proteínas do Nucleocapsídeo de Coronavírus/genética , Quinase I-kappa B/metabolismo , SARS-CoV-2/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/virologia , COVID-19/imunologia , COVID-19/metabolismo , Proteínas do Nucleocapsídeo de Coronavírus/metabolismo , Células HEK293 , Humanos , Imunidade Inata/imunologia , Interferon Tipo I/metabolismo , Interferons/metabolismo , NF-kappa B/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Cultura Primária de Células , Receptores do Ácido Retinoico/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Transdução de Sinais , Ubiquitinação
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