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1.
Food Chem ; 369: 130978, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34500209

RESUMO

In this paper, the effects of soybean protein isolate (SPI) on the formations of five heterocyclic aromatic amines (HAAs) in roasted pork were investigated. The levels of all five HAAs improved upon addition of 2.5% of SPI (P < 0.05). With higher SPI dosage, the levels of HAA decreased after seeing an increase. Two HAAs (MeIQx and 4,8-DiMeIQx) were inhibited by 10.0% of SPI, with the inhibitory efficiencies of 7.0 % and 85.7%, respectively. After being heated, the levels of both the free amino acids and carbonyl groups in the SPI were observed significantly increased, from 55.04 µg g·SPI-1 to 91.66 µg g·SPI-1 and from 123.85 ± 13.07 to 931.78 ± 32.56, respectively (P < 0.05). Therefore, the possible promotion mechanism of the SPI was speculated that the heated SPI would provide both the HAA precursors and carbonyls, which significantly promoted the Strecker degradation and generated more HAA intermediates (P < 0.05).

2.
J Hematol Oncol ; 14(1): 171, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663417

RESUMO

GTPase-activating protein (GAP) is a negative regulator of GTPase protein that is thought to promote the conversion of the active GTPase-GTP form to the GTPase-GDP form. Based on its ability to regulate GTPase proteins and other domains, GAPs are directly or indirectly involved in various cell requirement processes. We reviewed the existing evidence of GAPs regulating regulated cell death (RCD), mainly apoptosis and autophagy, as well as some novel RCDs, with particular attention to their association in diseases, especially cancer. We also considered that GAPs could affect tumor immunity and attempted to link GAPs, RCD and tumor immunity. A deeper understanding of the GAPs for regulating these processes could lead to the discovery of new therapeutic targets to avoid pathologic cell loss or to mediate cancer cell death.

3.
Virus Res ; 306: 198582, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34599934

RESUMO

We recently developed a Tembusu virus (TMUV)-specific monoclonal antibody (MAb) 12F11, which was found to recognize a long amino acid sequence between residues 8 and 77 of domain III of the envelope protein (EDIII). Here, the epitope recognized by MAb 12F11 was mapped using alanine substitutions combined with dissociation constant analysis. The findings, and prediction of tertiary structure of TMUV EDIII, showed that the MAb 12F11 epitope contained one critical residue and 13 peripheral residues. Moreover, the antigenic site was shown to span four loops (N-terminal region, AB, BC, and CD) and three ß-strands (A, B, and D). The present work contributes to the understanding of antigenic structure of TMUV envelope protein.

4.
Trials ; 22(1): 585, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479619

RESUMO

BACKGROUND: Major depressive disorder is the second leading cause of years lost to disability worldwide. Anyu Peibo Capsule has been shown to be effective and safe in phase II trials. METHODS: This clinical study is a multi-center, randomized, double-blinded, placebo-controlled, parallel-group, phase III trial of Anyu Peibo Capsule in China. The aim is to test whether the administration of Anyu Peibo Capsule compared to placebo improves clinical outcomes in adults (aged 18 to 65 years) with MDD. Patients will receive an 8-week treatment of Anyu Peibo Capsule 1.6 g per day or placebo. The primary outcome will be the change from baseline in the total score for the Montgomery-Asberg Depression Rating Scale at the end of the 8-week treatment. DISCUSSION: The trial aims to provide pivotal evidence for the efficacy and safety of Anyu Peibo Capsule in patients with major depressive disorder. TRIAL REGISTRATION: ClinicalTrials.gov NCT04210973 . Registered on December 26, 2019.


Assuntos
Transtorno Depressivo Maior , Adulto , China , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/tratamento farmacológico , Método Duplo-Cego , Humanos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
5.
Pharmacogenomics ; 22(13): 821-831, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34505535

RESUMO

Aim: The relationship between hyperuricemia and polymorphisms of transporter genes in coronary artery disease (CAD) patients in China remains unclear. Materials & methods: A total of 258 hyperuricemia patients with CAD and 242 control patients with CAD were recruited in this case-control study. Twenty-four SNPs in genes of ABCG2, PDZK1, URAT1, OAT4, GLUT9, ABCC4, NPT1 and NPT4 were genotyped using direct sequencing in all subjects. Results: The mutation of ABCG2 rs2231142 locus increases the risk of hyperuricemia, and there is a gene dose effect in the influence of mutant heterozygotes and homozygotes. rs3825017 in URAT1 and rs62293298 in GLUT9 were also confirmed to be associated with hyperuricemia. Conclusion: Age, weight, creatinine clearance rate, diuretics and SNPs on ABCG2, URAT1 and GLUT9 were all risk factors of hyperuricemia.

6.
Microorganisms ; 9(7)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34361971

RESUMO

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been used in the field of clinical microbiology since 2010. Compared with the traditional technique of biochemical identification, MALDI-TOF MS has many advantages, including convenience, speed, accuracy, and low cost. The accuracy and speed of identification using MALDI-TOF MS have been increasing with the development of sample preparation, database enrichment, and algorithm optimization. MALDI-TOF MS has shown promising results in identifying cultured colonies and rapidly detecting samples. MALDI-TOF MS has critical research applications for the rapid detection of highly virulent and drug-resistant pathogens. Here we present a scientific review that evaluates the performance of MALDI-TOF MS in identifying clinical pathogenic microorganisms. MALDI-TOF MS is a promising tool in identifying clinical microorganisms, although some aspects still require improvement.

7.
BMC Psychiatry ; 21(1): 396, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376171

RESUMO

BACKGROUND: Cognitive deficits are common in patients with schizophrenia (SCZ). Abnormal serum total bilirubin (TBIL) levels have been involved in cognitive deficits associated with neuropsychiatric diseases such as mild cognitive impairment and subcortical ischemic vascular disease. However, this relationship has not yet been fully investigated in patients with SCZ. Therefore, the aim of this study was to investigate the association between the serum TBIL concentration and cognitive deficits in SCZ patients and to determine whether a sex difference exists in the association. METHODS: A total of 455 participants were eligible and included in this cross-sectional study. Cognition was evaluated using the Montreal Cognitive Assessment. Serum TBIL concentration was measured with an automatic biochemistry analyzer according to the routine protocol in the hospital medical laboratory. RESULTS: Serum TBIL levels were lower in the cognition impairment group than in the cognition normal group in male patients. In contrast, serum TBIL levels tended to be increased in the cognition impairment group in female patients, although the difference was not significant. Further stepwise multiple regression analysis stratified by sex showed that serum TBIL was independently and positively associated with cognitive function in male patients but not in female patients. Moreover, the association between serum TBIL level and cognitive function was also identified by the propensity score matching (PSM) method in male patients, but not in female patients. CONCLUSION: These findings suggest that lower serum TBIL levels may be associated with cognitive impairment in male SCZ patients.


Assuntos
Esquizofrenia , Bilirrubina , Cognição , Estudos Transversais , Feminino , Humanos , Masculino , Esquizofrenia/complicações , Caracteres Sexuais
9.
J Clin Neurosci ; 91: 69-74, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34373061

RESUMO

ASH1L mutations have been identified with variable phenotypes, including intellectual disability, autism spectrum disorder (ASD), and multiple congenital anomalies (MCA). However, the mechanisms underlying this phenotypic variation remain unknown. Here, we present twin sisters exhibiting mild intellectual disability and seizures. Whole-exome sequencing of the family revealed a novel de novo heterozygous sequence variant, NM_018489.2: c.2678dup (p.Lys894*) in exon 3 of ASH1L which was estimated to be pathogenic. Furthermore, we reviewed previously reported ASH1L mutations in order to evaluate genotype-phenotype correlations for ASH1L variants. We found that patients with missense mutations in ASH1L appeared to present with more severe phenotypes and a higher likelihood of ASD than those with truncating mutations. The relationship between phenotype and genotype reported across several patients may help to explain the mechanisms underlying the phenotypic variation commonly observed between ASH1L mutations.


Assuntos
Transtorno do Espectro Autista , Proteínas de Ligação a DNA/genética , Histona-Lisina N-Metiltransferase/genética , Deficiência Intelectual , Convulsões , Transtorno do Espectro Autista/genética , Humanos , Deficiência Intelectual/genética , Mutação , Mutação de Sentido Incorreto , Fenótipo , Convulsões/genética
10.
Mol Med Rep ; 24(3)2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34278444

RESUMO

Long non­coding RNAs (lncRNAs) have been shown to function as crucial regulators in the progression of various types of cancer, including nasopharyngeal carcinoma (NPC). The aim of the present study was to investigate the mechanisms underlying the role of the FBXL19­AS1/microRNA (miR)­431/prostate and breast cancer overexpressed 1 (PBOV1) axis in the progression of NPC. The expression levels of FBXL19­AS1, miR­431 and PBOV1 were assessed by reverse transcription­quantitative PCR. The Cell Counting Kit­8 assay was utilized to detect cell viability. Cell migration and invasion were determined using a Transwell assay. The associations between FBXL19­AS1 and miR­431 or miR­431 and PBOV1 were verified via bioinformatics analysis, dual­luciferase and RNA­binding protein immunoprecipitation assays. It was demonstrated that the expression levels of FBXL19­AS1 and PBOV1 were upregulated in NPC tissues and cells, whereas miR­431 expression was downregulated. FBXL19­AS1 directly interacted with miR­431. FBXL19­AS1 silencing inhibited the viability, migration and invasion of C666­1 and SUNE1 cells, whereas these effects could be alleviated by suppressing miR­431. miR­431 could target the 3'­untranslated region of PBOV1. Overexpression of PBOV1 neutralized the miR­431­mediated suppression of NPC progression. Moreover, FBXL19­AS1 could regulate PBOV1 by sponging miR­431 in NPC cells. In conclusion, the lncRNA FBXL19­AS1 accelerated NPC progression via the miR­431/PBOV1 axis, suggesting that it may serve as a potential therapeutic target for patients with NPC.

11.
Genes Dis ; 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34222571

RESUMO

Despite the growing knowledge of T cell responses in COVID-19 patients, there is a lack of detailed characterizations for T cell-antigen interactions and T cell functions. Here, with a predicted peptide library from SARS-CoV-2 S and N proteins, restricted to three of the most prominent HLA-A alleles in the Asian population, we found that specific CD8+ T cell responses were identified in over 75% of COVID-19 convalescent patients (15/20). A total of 15 SARS-CoV-2 epitopes from the S and N proteins were identified, and among them, 3 dominant epitopes were further characterized. We found that an epitope from the N protein, N361-369 (KTFPPTEPK), was the most dominant epitope from our selected peptide library. Importantly, we discovered 2 N361-369-specific T cell receptors (TCRs) with high functional avidity that were independent of the CD8 co-receptor. These TCRs exhibited complementary cross-reactivity to several presently reported N361-369 mutant variants, as to the wild-type epitope. Further, the natural functions of these TCRs in the cytotoxic immunity against SARS-CoV-2 were determined with dendritic cells (DCs) and the lung organoid model. We found that the N361-369 epitope could be normally processed and endogenously presented by these different types of antigen presenting cells, to elicit successful activation and effective cytotoxicity of CD8+ T cells ex vivo. Our study evidenced potential mechanisms of cellular immunity to SARS-CoV-2, and illuminated potential ways of viral clearance in COVID-19 patients. These results indicate that utilizing CD8-independent TCRs against SARS-CoV-2-associated antigens may provide functional superiority that is beneficial for the adoptive cell immunotherapies based on natural or genetically engineered T cells. Additionally, this information is highly relevant for the development of the next-generation vaccines with protections against continuously emerged SARS-CoV-2 mutant strains.

12.
Ann Palliat Med ; 10(6): 6482-6492, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34237965

RESUMO

BACKGROUND: High levels of lipoprotein(a) (Lp(a)) is an independent risk factor for premature coronary heart disease (PCHD). It is also considered a residual risk for controlled low density lipoprotein cholesterol (LDL-C). Dietary control, exercise, and drugs have limited effects on the levels of Lp(a). Recently, mental health was found to be associated with lipid levels and increased risk of PCHD. However, the relationship between mental health and Lp(a) is still unknown. This study explored the association between mental health and Lp(a) levels in men with PCHD. METHODS: A retrospective, observational study was conducted. A total of 226 male patients with PCHD, aged 49.65±3.68 years, was included in this study. The control group consisted of 230 age-matched healthy male volunteers. Serum Lp(a) levels ≥30 mg/dL, as measured by the immunoturbidimetry method, were considered high. All participants received health related quality of life (HRQoL) scores using the self-assessed 36-Item Short Form Health Survey (SF-36). The HRQoL includes both a physical component summary (PCS) and a mental component summary (MCS). RESULTS: Patients with PCHD were found to have higher levels of Lp(a) (51.61±33.39 vs. 26.42±21.93, P<0.001), and lower MCS (35.83±4.21 vs. 39.85±4.12) and PCS scores (38.02±3.73 vs. 39.63±3.21) compared to healthy volunteers. The MCS score was negatively correlated with Lp(a) levels in the PCHD group (R=-0.295, P<0.001), but no correlation was detected in the control group. There was no relationship between the PCS score and Lp(a) levels in neither the PCHD group nor the healthy control group. Multivariate logistic regression analysis indicated that the MCS and PCS scores were negatively correlated with the risk of PCHD. CONCLUSIONS: These findings suggested that poor mental health may be associated with high levels of Lp(a) and increased risk of PCHD in men. Therefore, improving the mental state in men with PCHD may be crucial.


Assuntos
Doença da Artéria Coronariana , Lipoproteína(a) , Humanos , Masculino , Saúde Mental , Qualidade de Vida , Estudos Retrospectivos , Fatores de Risco
13.
J Zhejiang Univ Sci B ; 22(7): 590-598, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34269011

RESUMO

Although microRNA-155 (miR-155) is considered a pro-inflammatory mediator, cumulative evidence indicates that it also has anti-inflammatory effects in macrophages and dendritic cells. In this study, we identified the dramatic expression changes of more than half of potential miR-155-targeted genes upon lipopolysaccharide (LPS) stimulation; 223 genes were down-regulated and 85 genes were up-regulated, including suppressor of cytokine signaling 1 (SOCS1) and transforming growth factor-ß-activated kinase 1-binding protein 2 (TAB2), two well-known genes involved in miR-155-mediated regulation of the Toll-like receptor 4 (TLR4) signaling pathway. We also found that miR-155 acted as an anti-inflammatory mediator in the initial stage of LPS-induced inflammatory response mainly through repressing TAB2 protein translation, and as a pro-inflammatory mediator by down-regulating SOCS1 in the later stage. Meanwhile, overexpression of TAB2 3' untranslated region (UTR) in macrophages promoted the development of endotoxin tolerance by competing for binding with miR-155, which resulted in an elevated expression level of SOCS1 protein. These findings provide new insights for understanding the regulatory mechanisms in fine-tuning of LPS-induced innate immune response.

14.
BMJ Open ; 11(7): e042326, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215595

RESUMO

BACKGROUND: Cataract surgery is very important to prevent blindness, but its productivity and efficiency in China are unknown. Our study aimed to evaluate the geographical distribution of cataract surgeons and prospectively identify the factors associated with the increased productivity in cataract surgery and efficiency in outpatient ophthalmic services in rural Chinese hospitals. METHODS: Data were prospectively collated from various hospital datasets and the census registered by the geographical unit county. Prior to mapping, the geographical location data of counties were cross-linked with the equivalent ophthalmologist and service output data to create categories and map multiple data attributes. Descriptive statistical analyses were performed to characterise the data stratified by county. Linear regression analyses were used to explore the factors associated with the increased productivity/efficiency. RESULTS: The ophthalmologists, surgical productivity of ophthalmologists and outpatient efficacy of ophthalmologists significantly varied across counties. During the period between 2016 and 2018, the median (IQR) change in surgical productivity of and outpatient efficacy of ophthalmologists were 31.627 (-3.33 to 29.94) and 118.08 (-132.30 to 740.89). In the simple regression analysis for predictors of a high productivity change, only the increased number of phaco machine had statistical significance (p=0.003). In addition, only the gross domestic product per capita in 2016 was associated with an increased improvement in efficiency of outpatient services (p=0.008). CONCLUSIONS: This study demonstrated that the ophthalmologist productivity and the efficiency of outpatient services were unequally geographically distributed, and their predictors were identified. Further studies to elucidate the extent of the problem and improve the health service delivery models are required.


Assuntos
Extração de Catarata , Oftalmologistas , Oftalmologia , China , Hospitais de Condado , Humanos
15.
Acta Ophthalmol ; 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34137171

RESUMO

PURPOSE: To evaluate iris volume before and after pupil dilation using swept-source anterior segment optical coherence tomography (SS-ASOCT) and investigate the associated factors of iris volume and iris volume change after pupil dilation in patients with type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study was conducted in Zhongshan Ophthalmic Center among T2DM registered patients in the community of Guangzhou, China. Anterior chamber volume (ACV), iris volume, anterior chamber depth (ACD), angle opening distance at 500 µm (AOD 500) and pupil diameter were estimated using SS-ASOCT (CASIA; Tomey, Nagoya, Japan). Venous blood was taken for the measurement of glycosylated haemoglobin A1c (HbAlc). All biometric measurements were performed before and after pharmacologic pupil dilation. RESULTS: A total of 117 subjects were included in the analysis. The mean age (±SD) was 64.96 ± 7.75 years, and 62.4% were females. After pupil dilation, iris volume decreased in all eyes. Shorter duration of diabetes (p = 0.035), longer axial length (p < 0.001) and smaller pupil diameter (p < 0.001) were associated with larger iris volume. The change in iris volume per millimetre change in pupil diameter was 1.35mm3 /mm. Smaller baseline iris volume (p = 0.002) and higher HbA1c level (p = 0.010) were associated with smaller change in iris volume per millimetre change in pupil diameter, after adjusting for other factors. CONCLUSION: Iris volume can be estimated by SS-ASOCT. Diabetic duration was associated with static anatomy of iris volume, while HbA1c level indicated the dynamic response of iris volume. It is likely that diabetic duration and HbA1c level could affect the macroscopic and microscopic composition of the iris in the diabetic population.

16.
Int J Nanomedicine ; 16: 3091-3103, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33953557

RESUMO

Objective: To synthesize and determine the antifungal activity of AgBr-nanoparticles (NP) @CTMAB (cetyltrimethyl-ammonium bromide) against Candida albicans (C. albicans) for use in the field of denture cleaning. Methods: The morphology and structure of AgBr-NP@CTMAB were characterized by IR, UV-Vis, XRD and SEM. The antifungal potential of AgBr-NP@CTMAB against C. albicans was determined by colony formation assay and growth curve analysis. PMMA containing AgBr-NP@CTMAB was prepared, and the long-term antifungal efficacy was analyzed. The effect against C. albicans biofilm was analyzed by SEM and OD600 , and the color changes of the specimens were observed by stereomicroscopy after 1 week of incubation. Cytotoxicity to human oral gingival fibroblasts and oral mucosal epithelial cells was detected by Cell Counting Kit-8 (CCK-8) in vitro. Results: The compound showed a good crystalline phase, the presence of AgBr nanoparticles and the hybridization of CTMAB+ with AgBr-NPs. AgBr-NP@CTMAB showed significant antifungal activity against C. albicans at concentrations of 10 µg/mL and 20 µg/mL. PMMA specimens containing AgBr-NP@CTMAB showed no long-term antifungal effect against C. albicans biofilm. The clearance rate of C. albicans attached to PMMA was 44.73% after soaking in 10 µg/mL AgBr-NP@CTMAB solution for 30 min and 91.35% for 8 h. There was no significant residual cytotoxicity or visual color change after soaking. Significance: AgBr-NP@CTMAB showed promising potential treatment for denture cleaners.


Assuntos
Antifúngicos/síntese química , Antifúngicos/farmacologia , Cetrimônio/química , Nanopartículas/química , Polimetil Metacrilato/química , Antifúngicos/química , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Candida albicans/fisiologia , Técnicas de Química Sintética , Humanos , Nanotecnologia
17.
Plant Physiol ; 186(1): 110-124, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-33793888

RESUMO

Protein cysteine residues are susceptible to oxidative modifications that can affect protein functions. Proteomic techniques that comprehensively profile the cysteine redoxome, the repertoire of oxidized cysteine residues, are pivotal towards a better understanding of the protein redox signaling. Recent technical advances in chemical tools and redox proteomic strategies have greatly improved selectivity, in vivo applicability, and quantification of the cysteine redoxome. Despite this substantial progress, still many challenges remain. Here, we provide an update on the recent advances in proteomic strategies for cysteine redoxome profiling, compare the advantages and disadvantages of current methods and discuss the outstanding challenges and future perspectives for plant redoxome research.

18.
Plant Sci ; 307: 110894, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33902855

RESUMO

Cadmium (Cd) is a highly toxic element to living organisms, and its accumulation in the edible portions of crops poses a potential threat for human health. The molecular mechanisms underlying Cd detoxification and accumulation are not fully understood in plants. In this study, the involvement of a C-type ABC transporter, OsABCC9, in Cd tolerance and accumulation in rice was investigated. The expression of OsABCC9 was rapidly induced by Cd treatment in a concentration-dependent manner in the root. The transporter, localized on the tonoplast, was mainly expressed in the root stele under Cd stress. OsABCC9 knockout mutants were more sensitive to Cd and accumulated more Cd in both the root and shoot compared to the wild-type. Moreover, the Cd concentrations in the xylem sap and grain were also significantly increased in the knockout lines, suggesting that more Cd was distributed from root to shoot and grain in the mutants. Heterologous expression of OsABCC9 in yeast enhanced Cd tolerance along with an increase of intracellular Cd content. Taken together, these results indicated that OsABCC9 mediates Cd tolerance and accumulation through sequestration of Cd into the root vacuoles in rice.


Assuntos
Transporte Biológico/genética , Transporte Biológico/fisiologia , Cádmio/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Oryza/genética , Oryza/fisiologia , Raízes de Plantas/metabolismo , Brotos de Planta/metabolismo , Grão Comestível/metabolismo , Grão Comestível/fisiologia , Regulação da Expressão Gênica de Plantas , Brotos de Planta/genética
19.
Ann Palliat Med ; 10(4): 3960-3975, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33832291

RESUMO

BACKGROUND: The complication, pulmonary fibrosis (PF) secondary to COVID-19, may have a second wave of late mortality, given the huge number of individuals infected by COVID-19. However, the molecular mechanisms of PF secondary to COVID-19 haven't been fully elucidated, making the identification of novel strategies for targeted therapy challenging. This study aimed to systematically identify the molecular mechanisms and high-frequency core traditional Chinese medicine (TCM) targeting PF secondary to COVID-19 through network pharmacology and data mining. METHODS: The molecular mechanisms of PF secondary to COVID-19 were identified by mapping the COVID-19 differentially expressed gene and known targets associated with PF, protein-protein interactions network analysis, and enrichment pathway analysis; then the high-frequency core TCM targeting PF secondary to COVID-19 were identified by data mining and "Key targets related to PF secondary to COVID-19 - Ingredients" and "Key ingredients-key herbs" network analysis; and last we validated the interaction between the key ingredients and key targets by molecular docking. RESULTS: The molecular mechanisms of PF secondary to COVID-19 were mainly related to tumor necrosis factor (TNF) signaling pathway, cytokine-cytokine receptor interaction pathway, and NF-κB signaling pathway. Among these, cytokines interleukin 6 (IL-6), TNF, and IL-1ß were identified as the key targets associated with PF secondary to COVID-19. The high-frequency core TCM targeting these key targets were identified, including ingredients of quercetin, epigallocatechin-3-gallate, emodin, triptolide, resveratrol, and herb of Polygonum cuspidatum. Finally, our results were validated by quercetin and resveratrol both well docked to IL-6, TNF, and IL-1ß protein, with the estimated docking energy <0 kcal/mol. CONCLUSIONS: This study identified the cytokines-related molecular mechanisms of PF secondary to COVID-19, and the high-frequency core TCM against PF by targeting IL-6, TNF, and IL-1ß. Which provides new ideas for the discovery of small molecular compounds with potential therapeutic effects on PF secondary to COVID-19.


Assuntos
COVID-19 , Medicamentos de Ervas Chinesas , Fibrose Pulmonar , Mineração de Dados , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , SARS-CoV-2
20.
Front Immunol ; 12: 653189, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33828563

RESUMO

After the pandemic of COVID-19, neutralizing antibodies (NAbs) against SARS-CoV-2 have been developed for the prophylactic and therapeutic purposes. However, few methodologies are described in detail on how to rapidly and efficiently generate effective NAbs to SARS-CoV-2. Here, we integrated and optimized a strategically screening method for NAbs, which has enabled us to obtain SARS-CoV-2 receptor-binding domain (RBD) specific NAbs within 6 days, followed by additional 9 days for antibody production and function analysis. Using this method, we obtained 198 specific Abs against SARS-CoV-2 RBD from the blood samples of COVID-19 convalescent patients, and 96 of them showed neutralizing activity. At least 20% of these NAbs exhibited advanced neutralizing potency and high affinity, with the top two NAbs showing half-maximal inhibitory concentration (IC50) to block authentic SARS-CoV-2 at 9.88 and 11.13 ng/ml, respectively. Altogether, our study provides an effective methodology with high applicable value for discovering potential preventative and therapeutic NAbs for the emerging infectious diseases.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/sangue , COVID-19/imunologia , Humanos , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo
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