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1.
Psychol Mark ; 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34539053

RESUMO

The unprecedented crisis of COVID-19 posed severe negative consequences for consumers, marketers, and society at large. By investigating the effect of individuals' distance from the COVID-19 epicenter (i.e., the geographical area in which COVID-19 pandemic is currently most severe) on consumers' risk perception and subsequent behaviors, this research provides novel empirical findings that can offer practical insights for marketers. While intuitively, people expect individuals closer to the COVID-19 epicenter to generate a greater risk perception of the pandemic, empirical evidence from four studies provides consistent results for the opposite effect. We find that a closer (vs. farther) distance to the epicenter associates with lower (vs. higher) perceived risk of the pandemic, leading to less (vs. more) irrational consumption behaviors. We refer to this phenomenon as the "distance proximity effect," which holds for both physical and psychological distances. We further demonstrated that this effect is mediated by consumers' perception of uncertainty and moderated by individuals' risk aversion tendency. The current research contributes to the literature of consumers' risk perception and irrational consumption by highlighting a novel factor of distance proximity. It also offers some timely insights into managing and intervening COVID-19 related issues inside and outside an epicenter.

2.
Exp Cell Res ; 407(2): 112784, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34508746

RESUMO

Inflammation is an essential factor contributing to sepsis-induced endothelial cell (EC) activation. Interleukin-35 (IL-35) is an anti-inflammatory/immunosuppressive cytokine that exerts protective effects on many inflammatory diseases. In this study, we investigated the effects of IL-35 on lipopolysaccharide (LPS)-induced EC activation and the potential underlying mechanism. Human umbilical vein endothelial cells (HUVECs) were incubated with LPS (1 µg/ml) for 24 h and then cocultured with different concentrations (0, 1, 10, or 100 ng/ml) of recombinant human IL-35 (rhIL-35) for 12 h. Flow cytometry analysis revealed that IL-35 inhibited LPS-induced HUVEC apoptosis in a dose-dependent manner. RT-qPCR and Western blot analyses showed significantly higher mRNA and protein levels of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and the inflammatory factors IL-6 and IL-8 in the LPS group than in the control group. These changes were alleviated by IL-35 treatment, suggesting that IL-35 protects ECs by downregulating inflammation. Furthermore, IL-35 induced signal transducer and activator of transcription 1 (STAT1) and STAT4 activation and promoted their interaction. Blocking STAT1 or STAT4 expression by fludarabine (STAT1 inhibitor) treatment or siRNA-STAT4-interfering fragment transfection inhibited the protective effect of IL-35 on ECs. Moreover, we observed a similar protective effect of IL-35 treatment on ECs in a mouse sepsis model induced by intraperitoneal LPS injection. This study indicated that IL-35 exerts anti-inflammatory and antiapoptotic effects on LPS-induced EC activation by activating the STAT1 and STAT4 signaling pathways.

3.
J Infect Dev Ctries ; 15(8): 1074-1079, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34516413

RESUMO

INTRODUCTION: Public life in China is gradually returning to normal with strong measures in coronavirus 2019 (COVID-19) control. Because of the long-term effects of COVID-19, medical institutions had to make timely adjustments to control policies and priorities to balance between COVID-19 prevention and daily medical services. METHODOLOGY: The framework for infection prevention and control in the inpatient department was effectively organized at both hospital and department levels. A series of prevention and control strategies was implemented under this leadership: application of rigorous risk assessment and triage before admission through a query list; classifying patients into three risk levels and providing corresponding medical treatment and emergency handling; establishing new ward visiting criteria for visitors; designing procedures for PPE and stockpile management; executing specialized disinfection and medical waste policies. RESULTS: Till June 2020, the bed occupancy had recovered from 20.0% to 88.1%. In total, 13045 patients were received in our hospital, of which 54 and 127 patients were identified as high-risk and medium-risk, respectively, and 2 patients in the high-risk group were eventually laboratory-confirmed with COVID-19. No hospital-acquired infection of COVID-19 has been observed since the emergency appeared. CONCLUSIONS: The strategies ensured early detection and targeted prevention of COVID-19 following the COVID-19 pandemic, which improved the recovery of medical services after the pandemic.


Assuntos
COVID-19/prevenção & controle , Infecção Hospitalar/prevenção & controle , Hospitais/estatística & dados numéricos , Controle de Infecções/métodos , COVID-19/epidemiologia , China/epidemiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/virologia , Hospitalização/estatística & dados numéricos , Hospitais/normas , Humanos , Controle de Infecções/instrumentação , Pacientes Internados/estatística & dados numéricos , Isolamento de Pacientes/métodos , Equipamento de Proteção Individual , Medição de Risco , Triagem
4.
Artigo em Inglês | MEDLINE | ID: mdl-34493193

RESUMO

Mesenchymal stem cells (MSCs) are multipotent progenitor cells that play crucial roles in the microenvironment of injured tissues. The potential therapeutics of MSCs have attracted extensive attention for several diseases such as acute respiratory distress syndrome (ARDS) and novel coronavirus disease 2019 (COVID-19) pneumonia. MSC-extracellular vesicles have been isolated from MSC-conditioned media (MSC-CM) with similar functional effects as parent MSCs. The therapeutic role of MSCs can be achieved through the balance between the inflammatory and regenerative microenvironments. Clinical settings of MSCs and their extracellular vesicles remain promising for many diseases, such as ARDS and pneumonia. However, their clinical applications remain limited due to the cost of growing and storage facilities of MSCs with a lack of standardized MSC-CM. This review highlights the proposed role of MSCs in pulmonary diseases and discusses the recent advances of MSC application for pneumonia and other lung disorders.

6.
Rev Assoc Med Bras (1992) ; 67(4): 590-596, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34495066

RESUMO

OBJECTIVE: Polycystic ovary syndrome can be divided into different subtypes, including insulin resistance and hyperandrogenism. The aim of this study was to investigate the relationship between serum asprosin levels and polycystic ovary syndrome subtypes. METHODS: A total of 93 women with polycystic ovary syndrome and 77 healthy women as controls were selected for this study. The clinical and laboratory data were compared between the Polycystic ovary syndrome group and the control group. The Polycystic ovary syndrome group was further divided into subgroups: (1) women with or without hyperandrogenism (polycystic ovary syndrome hyperandrogenism and Polycystic ovary syndrome none-hyperandrogenism, respectively) and (2) women with or without insulin resistance (polycystic ovary syndrome insulin resistance and Polycystic ovary syndrome none-insulin resistance, respectively). Serum asprosin was measured by using enenzyme-linked immunosorbent assay. RESULTS: Serum asprosin levels showed no significant difference between the polycystic ovary syndrome and control groups. However, it was significantly lower in the Polycystic ovary syndrome HA and insulin resistance groups compared with the respective Polycystic ovary syndrome none-hyperandrogenism and none-insulin resistance groups (p<0.05). In the Polycystic ovary syndrome group, serum asprosin was negatively correlated with body mass index, luteinizing hormone, testosterone, basal antral follicles, fasting insulin, homeostatic model assessment of insulin resistance, and triglycerides. After adjusting for body mass index, the correlations were not significant, and asprosin was only positively correlated with prolactin (prolactin; r=0.426, p<0.001). CONCLUSION: Our study shows that women with polycystic ovary syndrome hyperandrogenism or insulin resistance exhibit significantly lower serum asprosin levels compared with controls, and the lower asprosin level directly correlated with prolactin level.


Assuntos
Hiperandrogenismo , Resistência à Insulina , Hormônios Peptídicos , Síndrome do Ovário Policístico , Índice de Massa Corporal , Estudos Transversais , Feminino , Fibrilina-1 , Humanos , Insulina , Proteínas dos Microfilamentos , Fragmentos de Peptídeos , Síndrome do Ovário Policístico/complicações , Testosterona
8.
J Ethnopharmacol ; : 114655, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34537284

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammatory responses are associated wieh the pathophysiology of depression. Ginsenoside Rb1 (Rb1) exerts antidepressant effect, but the relationship between its activity and inflammation remains unclear. AIM OF THE STUDY: In this study, the antidepressant-like effect and underlying mechanisms of Rb1 were been investigated. MATERIALS AND METHODS: The neuroinflammatory mouse model of lipopolysaccharide (LPS)-induced acute depression-like behavior was employed to detect the action of Rb1. An integrative strategy combining the identification of prototype (Rb1) and its metabolites in vivo with network pharmacology analysis was used to explore therapeutic mechanisms of these ingredients. The putative targets and signalings were experimentally validated. The antidepressant-like effect of F2, the metabolite of Rb1, was firstly evaluated. RESULTS: Rb1 significantly ameliorated LPS-induced depressive-like behavior. Rb1 and its metabolites (Rd, F2, compound K, Rh2, Rg3, PPD) were identified and then a disease-component-target network was established. Experimental validation showed that Rb1 inhibited peripheral and hippocampal inflammation via MAPK/NF-κB signaling. In inflammatory-mediated depression state, Rb1 improved impaired glucocorticoid receptor, suppressed indoleamine 2,3-dioxygenase activity, increased 5-HT level and 5-HT1A receptor expression. Additionally, F2 was firstly discovered to exert antidepressant-like effect, and it existed higher activity than Rb1 against depression. CONCLUSION: The study highlighted the potential of Rb1 and F2 as healthy supplement or agent for inflammation-induced depression.

9.
Sheng Wu Gong Cheng Xue Bao ; 37(8): 2890-2902, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34472306

RESUMO

The evolution, structure and antigenic epitopes prediction of Rana dybowskii antimicrobial peptide dybowskin-1ST were carried out using bioinformatics software available online. Its antibacterial mechanism and structural properties were analyzed, and its activity was verified by applying wound healing assay in mice and bacteriostatic assay in vitro. This provides the theoretical basis for the improvement of parental peptide and the development of novel derivative peptides. The software MEGA_X were used to conduct homology alignment and to construct a phylogenetic tree. The online software ProtParam, ProtScale, PeptideCutter, signal, TMHMM Server were respectively used to predict the physicochemical parameters, hydrophilia/hydrophobicity, shear sites, signal peptides, and transmembrane domains of dybowskin-1ST. The online software SOPMA, Jpred4, DNAstar Protean were used to predict the secondary structure of dybowskin-1ST, and SWISS-MODEL, I-TASSER were used to predict the tertiary structure. ABCpred and SYFPEITHI were respectively used to predict its B-and T-cell epitopes. The effect of dybowskin-1ST on the wound healing was observed on experimental mice. Kirby-Bauer method and dilution method were used to determine the bacteriostatic activity of dybowskin-1ST. The dybowskin-1ST consists of 59 amino acid residues, of which leucine accounts for 16.9%, with a molecular formula of C318H510N80O93S2. Its theoretical isoelectric point is 5.10 and the charge is -2. The dybowskin-1ST and dybowskin-1CDYa are closely related phylogenetically. The secondary structure of dybowskin-1ST predicted by the three methods were similar, which consisted of α-helix (44.07%), extended strand (16.95%), ß-turns (3.39%), and random coil (35.39%). The prediction of tertiary structure showed that dybowskin-1ST was mainly composed of α-helix, and it was regarded as a hydrophilic protein with signal peptide sequence. Subcellular localization analysis showed that the probability of secreting the mitochondrial targeted peptides was 0.944. Dybowskin-1ST is an extracellular protein with no transmembrane structure region, but contains seven phosphorylation sites, three T-cell epitopes and eight B-cell epitopes. The dybowskin-1ST promoted wound healing and effectively inhibited the growth of Escherichia coli and Staphylococcus aureus. However, it had limited antibacterial activity against fungi and drug-resistant bacteria. Although the structure of dybowskin-1ST is rich in α-helix, the verification experiments showed that its antibacterial ability needs to be enhanced. The reason may be that it is a negatively charged and hydrophilic protein, and amino acid modification with the aim of increasing the number of positive charges and changing the hydrophobicity may be used to obtain derived peptides with enhanced activity.


Assuntos
Ranidae , Sequência de Aminoácidos , Animais , Camundongos , Filogenia , Proteínas Citotóxicas Formadoras de Poros , Estrutura Secundária de Proteína
10.
Cancer Discov ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479870

RESUMO

Chronic and low-grade inflammation associated with persistent bacterial infections has been linked to colon tumor development; however, the impact of transient and self-limited infections in bacterially-driven colon tumorigenesis has remained enigmatic. Here we report that UshA is a novel genotoxin in attaching/effacing (A/E) pathogens, which includes the human pathogens enteropathogenic Escherichia coli (EPEC), enterohemorrhagic E. coli (EHEC), and their murine equivalent Citrobacter rodentium (CR). UshA harbors direct DNA digestion activity with a catalytic histidine-aspartic acid dyad. Injected via the Type III Secretion System (T3SS) into host cells, UshA triggers DNA damage and initiates tumorigenic transformation during infections in vitro and in vivo. Moreover, UshA plays an indispensable role in CR infection-accelerated colon tumorigenesis in genetically susceptible ApcMinΔ716/+ mice. Collectively, our results reveal that UshA, functioning as a bacterial T3SS-dependant genotoxin, plays a critical role in prompting transient and noninvasive bacterial infection-accelerated colon tumorigenesis in mice.

11.
Eur J Histochem ; 65(3)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34474553

RESUMO

Osteosarcoma (OS) is the most prevalent malignant bone tumor in children and young adults. There is an urgent need for a novel biomarker related to the prognosis of OS. We performed a meta-analysis incorporating six independent datasets and performed a survival analysis with one independent dataset GSE21257 in the GEO database for gene screening. The results revealed that one potential biomarker related to OS survival, POGZ was the most significantly upregulated gene. We also verified that the POGZ was overexpressed in clinical samples. The survival analysis revealed that POGZ is associated with a poor prognosis in OS. Moreover, flow cytometry analysis of isolated OS cells demonstrated that OS cells were arrested in the G1 phase after POGZ knockdown. The RNA-seq results indicated that POGZ was co-expressed with CCNE1 and CCNB1. Pathway analysis showed that genes associated with high expression levels of POGZ were related to the cell cycle pathway. A cell model was constructed to detect the effects of POGZ. After POGZ knockdown, OS cell proliferation, invasion and migration were all decreased. Therefore, POGZ is an important gene for evaluating the prognosis of OS patients and is a potential therapeutic target.

12.
BMC Public Health ; 21(1): 1619, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488700

RESUMO

BACKGROUND: To evaluate global burden of refraction disorders by year, age, region, gender, socioeconomic status and other national characteristics in terms of disability adjusted life years (DALYs) and prevalence from Global Burden of Disease (GBD) study 2019 and World Bank Open Data 2019. METHODS: Global, regional, and national DALY numbers, crude DALY rates, age-standardized DALY and prevalence rates of refraction disorders were acquired from the GBD study 2019. Mobile cellular subscriptions, urban population, GDP per capita, access to electricity and total fertility rate were obtained from the World Bank to explore the factors that influenced the health burden of refraction disorders. Kruskal-Wallis test, linear regression and multiple linear regression were performed to evaluate the associations between the health burden with socioeconomic levels and other national characteristics. Wilcoxon Signed-Rank Test was used to investigate the gender disparity. RESULTS: Globally, age-standardized DALY rates of refraction disorders decreased from 88.9 (95% UI: 60.5-120.3) in 1990 to 81.5 (95% UI: 55.0-114.8) in 2019, and might fall to 73.16 (95% UI: 67.81-78.51) by 2050. Age-standardized prevalence rates would also reduce to 1830 (95% UI: 1700-1960) by 2050, from 2080 (95% UI: 1870-2310) in 1990 to 1960 (95% UI: 1750-2180) in 2019. In low SDI region, age-standardized DALY rates (equation: Y = 114.05*X + 27.88) and prevalence rates (equation: Y = 3171.1*X + 403.2) were positively correlated with SDI in linear regression respectively. East Asia had the highest blindness rate caused by refraction disorders in terms of age-standardized DALY rates (11.20, 95% UI: 7.38-16.36). Gender inequality was found among different age groups and SDI regions. CONCLUSION: Health burden of refraction disorders decreased in recent years, and may continue to alleviate in the next three decades. Older ages, females and lower socioeconomic status were associated with higher refraction disorders health burden.


Assuntos
Pessoas com Deficiência , Carga Global da Doença , Idoso , Feminino , Saúde Global , Humanos , Pessoa de Meia-Idade , Prevalência , Anos de Vida Ajustados por Qualidade de Vida
13.
J Comput Biol ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34529511

RESUMO

A major challenge in cancer genomics is to identify cancer driver genes and modules. Most existing methods to identify cancer driver modules (iCDM) identify groups of genes whose somatic mutational patterns exhibit either mutual exclusivity or high coverage of patient samples, without considering other biological information from multiomics data sets. Here we integrate mutual exclusivity, coverage, and protein-protein interaction information to construct an edge-weighted network, and present a graph clustering approach based on symmetric non-negative matrix factorization to iCDM. iCDM was tested on pan-cancer data and the results were compared with those from several advanced computational methods. Our approach outperformed other methods in recovering known cancer driver modules, and the identified driver modules showed high accuracy in classifying normal and tumor samples.

14.
Front Immunol ; 12: 730483, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512666

RESUMO

The antiviral innate immunity is the first line of host defense against viral infection. Mitochondrial antiviral signaling protein (MAVS, also named Cardif/IPS-1/VISA) is a critical protein in RNA virus-induced antiviral signaling pathways. Our previous research suggested that E3 ubiquitin-protein ligases RING-finger protein (RNF90) negatively regulate cellular antiviral responses by targeting STING for degradation, though its role in RNA virus infection remains unknown. This study demonstrated that RNF90 negatively regulated RNA virus-triggered antiviral innate immune responses in RNF90-silenced PMA-THP1 cells, RNF90-deficient cells (including HaCaTs, MEFs, and BMDMs), and RNF90-deficient mice. However, RNF90 regulated RNA virus-triggered antiviral innate immune responses independent of STING. RNF90 promoted K48-linked ubiquitination of MAVS and its proteasome-dependent degradation, leading to the inhibition of innate immune responses. Altogether, our findings suggested a novel function and mechanism of RNF90 in antiviral innate immunity.

15.
MRS Commun ; : 1-9, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34513262

RESUMO

In vitro thrombogenicity test systems require co-cultivation of endothelial cells and platelets under blood flow-like conditions. Here, a commercially available perfusion system is explored using plasma-treated cyclic olefin copolymer (COC) as a substrate for the endothelial cell layer. COC was characterized prior to endothelialization and co-cultivation with platelets under static or flow conditions. COC exhibits a low roughness and a moderate hydrophilicity. Flow promoted endothelial cell growth and prevented platelet adherence. These findings show the suitability of COC as substrate and the importance of blood flow-like conditions for the assessment of the thrombogenic risk of drugs or cardiovascular implant materials. Supplementary Information: The online version contains supplementary material available at 10.1557/s43579-021-00072-6.

16.
Analyst ; 146(18): 5533-5541, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34515705

RESUMO

It is a pre-requisite to ionize analyte molecules efficiently for detection by laser desorption/ionization mass spectrometry. Here, we report a conceptual demonstration of cationizing neutral small molecules which are typically difficult to be ionized with the traditional organic matrices due to their low proton/cation affinity values. Our strategy features generating radical cations from site-specifically carboxylated 10-(4-carboxyphenyl)-10H-phenothiazine-3,7-dicarboxylic acid (PTZ(A)2-Ph(A)) with a laser, and anchoring the chlorine ion from NaCl through covalent bond-like bridging interactions with the N/S atoms in the heterocyclic structure. This "Maverick" design allows a dramatic change of the energy landscape of analyte sodiation with an enhanced efficiency. We have synthesized two families of compounds based on the model structures of phenothiazine (PTZ) and phenoxazine (PXZ) and their carboxylated derivatives, and performed comparison between them or against the traditional organic matrices in a systematic format. We have demonstrated that PTZ(A)2-Ph(A) is outstanding as a novel MALDI matrix for the detection of oligosaccharides and amino acids, with an ultra-clean background baseline and high signal-to-noise ratios (up to dozens of times better than the traditional matrices). This work provides a new method for the cationization of neutral small molecules in a distinct mechanism, inspiring the development of next-generation matrices for sensitive detection of hard-to-be-ionized molecules by MALDI MS.


Assuntos
Oligossacarídeos , Prótons , Lasers , Fenotiazinas , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
17.
Nucleic Acids Res ; 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34534340

RESUMO

With the accumulation of massive data sets from high-throughput experiments and the rapid emergence of new types of omics data, gene sets have become more diverse and essential for the refinement of gene annotation at multidimensional levels. Accordingly, we collected and defined 236 007 gene sets across different categories for 44 plant species in the Plant Gene Set Annotation Database (PlantGSAD). These gene sets were divided into nine main categories covering many functional subcategories, such as trait ontology, co-expression modules, chromatin states, and liquid-liquid phase separation. The annotations from the collected gene sets covered all of the genes in the Brassicaceae species Arabidopsis and Poaceae species Oryza sativa. Several GSEA tools are implemented in PlantGSAD to improve the efficiency of the analysis, including custom SEA for a flexible strategy based on customized annotations, SEACOMPARE for the cross-comparison of SEA results, and integrated visualization features for ontological analysis that intuitively reflects their parent-child relationships. In summary, PlantGSAD provides numerous gene sets for multiple plant species and highly efficient analysis tools. We believe that PlantGSAD will become a multifunctional analysis platform that can be used to predict and elucidate the functions and mechanisms of genes of interest. PlantGSAD is publicly available at http://systemsbiology.cau.edu.cn/PlantGSEAv2/.

18.
J Cosmet Dermatol ; 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496123

RESUMO

BACKGROUND: The nose is located in the middle of the face; therefore, nasal scarring will bring a significant psychological impact on patients. Although there are many treatment methods for depressed scars, these methods have varying degrees of efficacy and all carry certain adverse effects. A better treatment method is urgent to be found. In this study, the effect of micro-plasma radiofrequency technology combined with subcision to treat nasal depressed scars is evaluated. METHODS: 18 Chinese patients with nasal depressed scars participated in this study. All patients received one session of micro-plasma radiofrequency treatment first. 2 months later, subcision combined with micro-plasma radiofrequency technology was performed on them at 6-month intervals, and a total of 2 sessions of combined treatment were performed. Goodman and Baron Scale was used to evaluate nasal scars before treatment and 6 months after the final session. RESULTS: All 18 patients in this study had Grade 4 nasal scars before treatment. 6 months after the end of treatment, 13 patients (72.2%) showed excellent or near total improvement, and 5 patients (27.8%) showed marked improvement. No adverse side effects were observed during treatment. Patient self-evaluation indicated that all patients were satisfied with the cosmetic outcomes. CONCLUSIONS: In this study, we explored a new treatment method for nasal depressed scars. We used micro-plasma radiofrequency technology combined with subcision to treat nasal depressed scars and obtained relatively satisfactory results with no adverse effects.

19.
Bioengineered ; 12(1): 5892-5903, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34482807

RESUMO

Bladder cancer is one of the most severe genitourinary cancers, causing high morbidity worldwide. However, the underlying molecular mechanism is not clear, and it is urgent to find target genes for treatment. G-protein-coupled receptors are currently a target of high interest for drug design. Thus, we aimed to identify a target gene-related to G-protein-coupled receptors for therapy. We used The Cancer Genome Atlas (TCGA) and DepMap databases to obtain the expression and clinical data of RGS19. The results showed that RGS19 was overexpressed in a wide range of tumor, especially bladder cancer. We also explored its effect on various types of cancer. High expression of RGS19 was also shown to be significantly associated with poor prognosis. Cell models were constructed for cell cycle detection. shRGS19 can halt the cell cycle at a polyploid point. RGS19 is a G-protein-coupled receptor signaling pathway-related gene with a significant effect on survival. We chose RGS19 as a therapeutic target gene in bladder cancer. The drug GSK1070916 was found to inhibit the effect of RGS19 via cell rescue experiments in vitro.

20.
Eur J Med Chem ; 226: 113845, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34534838

RESUMO

To resolve the problem of drug resistance caused by epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer, we used the principle of collocation to design and synthesize a series of aminopyrimidine derivatives with 4,5,6,7-tetrahydrothieno [3,2-c]pyridine side chains (according to the binding mode of AZD9291 to EGFRT790M) for use as EGFRL858R/T790M kinase inhibitors. The most promising compound A12, a non-covalently bound reversible inhibitor, showed excellent kinase inhibitory activity against EGFRL858R/T790M, with an IC50 value of 4.0 nM and more than 42-fold selectivity for EGFRWT (IC50 = 170.0 nM). Moreover, compound A12 showed strong anti-proliferative activity against H1975 cells, with IC50 value of 0.086 µΜ. Additionally, the effective inhibition of cell migration and the promotion of apoptosis by A12 verified its mechanism of action, as a selective inhibitor of EGFRL858R/T790M.

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