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Aphis spiraecola Patch is one of the most economically important tree fruit pests worldwide. The pyrethroid insecticide lambda-cyhalothrin is commonly used to control A. spiraecola. In this 2-year study, we quantified the resistance level of A. spiraecola to lambda-cyhalothrin in different regions of the Shaanxi province, China. The results showed that A. spiraecola had reached extremely high resistance levels with a 174-fold resistance ratio (RR) found in the Xunyi region. In addition, we compared the enzymatic activity and expression level of P450 genes among eight A. spiraecola populations. The P450 activity of A. spiraecola was significantly increased in five regions (Xunyi, Liquan, Fengxiang, Luochuan, and Xinping) compared to susceptible strain (SS). The expression levels of CYP6CY7, CYP6CY14, CYP6CY22, P4504C1-like, P4506a13, CYP4CZ1, CYP380C47, and CYP4CJ2 genes were significantly increased under lambda-cyhalothrin treatment and in the resistant field populations. A L1014F mutation in the sodium channel gene was found and the mutation rate was positively correlated with the LC50 of lambda-cyhalothrin. In conclusion, the levels of lambda-cyhalothrin resistance of A. spiraecola field populations were associated with P450s and L1014F mutations. Our combined findings provide evidence on the resistance mechanism of A. spiraecola to lambda-cyhalothrin and give a theoretical basis for rational and effective control of this pest species.
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Afídeos , Inseticidas , Piretrinas , Canais de Sódio Disparados por Voltagem , Animais , Afídeos/genética , Piretrinas/farmacologia , Nitrilas/farmacologia , Mutação , Canais de Sódio Disparados por Voltagem/genética , Expressão Gênica , Inseticidas/farmacologia , Resistência a Inseticidas/genéticaRESUMO
Rhopalosiphum padi is a global pest that poses a significant threat to wheat crops and has developed resistance to various insecticides. G protein-coupled receptors (GPCRs), known for their crucial role in signaling and biological processes across insect species, have recently gained attention as a potential target for insecticides. GPCR has the potential to contribute to insect resistance through the regulation of P450 gene expression. However, GPCRs in R. padi remained unexplored until this study. We identified a total of 102 GPCRs in R. padi, including 81 receptors from family A, 10 receptors from family B, 8 receptors from family C, and 3 receptors from family D. Among these GPCR genes, 16 were up-regulated in both lambda-cyhalothrin and bifenthrin-resistant strains of R. padi (LC-R and BIF-R). A relaxin receptor gene, RpGPCR41, showed the highest up-regulated expression in both the resistant strains, with a significant increase of 14.3-fold and 22.7-fold compared to the susceptible strain (SS). RNA interference (RNAi) experiments targeting the relaxin receptor significantly increase the mortality of R. padi when exposed to the LC50 concentration of lambda-cyhalothrin and bifenthrin. The expression levels of five P450 genes (RpCYP6CY8, RpCYP6DC1, RpCYP380B1, RpCYP4CH2, and RpCYP4C1) were significantly down-regulated following knockdown of RpGPCR41 in LC-R and BIF-R strains. Our results highlight the involvement of GPCR gene overexpression in the resistance of R. padi to pyrethroids, providing valuable insights into the mechanisms underlying aphid resistance and a potential target for aphid control.
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Afídeos , Resistência a Inseticidas , Inseticidas , Piretrinas , Receptores Acoplados a Proteínas G , Animais , Afídeos/efeitos dos fármacos , Afídeos/genética , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Inseticidas/toxicidade , Nitrilas/farmacologia , Nitrilas/toxicidade , Piretrinas/farmacologia , Piretrinas/toxicidade , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Interferência de RNARESUMO
CRF-like diuretic hormone receptor (CRF/DHR), also known as DH44R in insects, are G-protein coupled receptors (GPCRs) that play a role in regulating osmotic balance in various insect species. These receptors have the potential to be targeted for the development of insecticides. However, our understanding of the role of DHR genes in aphids, including Rhopalosiphum padi, a major wheat pest, is currently limited. In this study, we isolated and characterized two R. padi DHRs (RpDHR1 and RpDHR2). The expression levels of RpDHR1 increased after starvation and were restored after re-feeding. The expression levels of RpDHR1 gene decreased significantly 24 h after injection of dsRNA targeting the gene. Knockdown of RpDHR1 increased aphid mortality under starvation conditions (24, 36, 48 and 60 h). Under starvation and desiccation condition, the aphid mortality decreased after knockdown of RpDHR1. This is the first study to report the role of DHR genes in the starvation and desiccation response of aphids. The results suggest that RpDHR1 is involved in the resistance of R. padi to starvation and dehydration, making it a potential target for insecticide development. Novel insecticides could be created by utilizing DHR agonists to disrupt the physiological processes of insect pests.
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Afídeos , Proteínas de Insetos , Animais , Afídeos/genética , Afídeos/fisiologia , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Inanição/genética , Dessecação , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , FilogeniaRESUMO
Uridine diphosphate-glucuronosyltransferases (UGTs) are major multifunctional detoxification phase II enzymes involved in the metabolic detoxification of xenobiotics. However, their roles in insecticides resistance are still unclear. In this study, we identified two UGTs genes (UGT2B13 and UGT2C1) in Rhopalosiphum padi, a serious insect pest of wheat worldwide. Bioassays results showed that the resistance ratio of R. padi resistance strain (LC-R) to lambda-cyhalothrin (LC) was 2963.8 fold. The roles of UGT2B13 and UGT2C1 in lambda-cyhalothrin resistance were evaluated. Results indicated that the UGTs contents were significantly increased in the LC resistant strain of R. padi. UGT2B13 and UGT2C1 were significantly overexpressed in the LC-R strain. Transcription levels of UGT2B13 and UGT2C1 were relatively higher in the gut of LC-R strain. RNA interference (RNAi) of UGT2B13 or UGT2C1 significantly decreased the UGTs contents of the LC-R aphids and increased mortality of R. padi exposure to the LC50 concentration of LC. This study provides a new view that UGTs are involved in LC resistance of R. padi. The findings will promote further work to detailed the functions of UGTs in the metabolism resistance of insects to insecticides.
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Afídeos , Inseticidas , Piretrinas , Animais , Inseticidas/farmacologia , Piretrinas/farmacologia , Nitrilas/farmacologia , Resistência a Inseticidas/genéticaRESUMO
Ampelopsis grossedentata (AG) is mainly distributed in Chinese provinces and areas south of the Yangtze River Basin. It is mostly concentrated or scattered in mountainous bushes or woods with high humidity. Approximately 57 chemical components of AG have been identified, including flavonoids, phenols, steroids and terpenoids, volatile components, and other chemical components. In vitro studies have shown that the flavone of AG has therapeutic properties such as anti-bacteria, anti-inflammation, anti-oxidation, enhancing immunity, regulating glucose and lipid metabolism, being hepatoprotective, and being anti-tumor with no toxicity. Through searching and combing the related literature, this paper comprehensively and systematically summarizes the research progress of AG, including morphology, traditional and modern uses, chemical composition and structure, and pharmacological and toxicological effects, with a view to providing references for AG-related research.
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Ampelopsis , Medicamentos de Ervas Chinesas , Plantas Medicinais , Ampelopsis/química , Medicamentos de Ervas Chinesas/química , Flavonoides/farmacologia , Flavonoides/química , Glucose , Compostos Fitoquímicos/farmacologia , Etnofarmacologia , Extratos Vegetais/químicaRESUMO
Insect octopamine (OA) receptors are G-protein coupled receptors (GPCRs) that play essential roles in physiological and behavioural processes. However, there is little information about the function of OA receptors in the aphids' response to stress. From the genome sequence of Rhopalosiphum padi genome sequence, a cosmopolitan cereal pest, we identified six OA receptor genes RpOAMB, RpOctR, RpOctß1R, RpOctß2R, RpOctß3R, RpOctR-like with two, one, one, four, four, seven exons, respectively. All the OA receptors contain seven transmembrane domains, which were the signature of GPCRs. Our results showed that (1) the contents of OA increased significantly after food starvation, (2) the transcription levels of RpOAMB, RpOctR, RpOctß2R and RpOctß3R increased after starvation and were restored after re-feeding, and (3) the expression levels of these four genes decreased significantly 48 h post-injection of dsRNA that targeted the respective genes. Knockdown of RpOctR, RpOctß2R or RpOctß3R genes significantly increased aphid mortality under 24 h starvation conditions. Mortality of R. padi injected with dsRpOctR or dsRpOctß2R was significantly higher than control under 48 h starvation treatments. This is the first report on the role of OA receptors in the starvation response of aphids. The current study provides knowledge for a better understanding the physiological roles of insect OA receptors.
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Afídeos , Animais , Afídeos/genética , Receptores de Amina BiogênicaRESUMO
BACKGROUND: Alternative splicing (AS) plays important roles in transcriptome and proteome diversity. Its dysregulation has a close affiliation with oncogenic processes. This study aimed to evaluate AS-based biomarkers by machine learning algorithms for lung squamous cell carcinoma (LUSC) patients. METHOD: The Cancer Genome Atlas (TCGA) database and TCGA SpliceSeq database were utilized. After data composition balancing, Boruta feature selection and Spearman correlation analysis were used for differentially expressed AS events. Random forests and a nested fivefold cross-validation were applied for lymph node metastasis (LNM) classifier building. Random survival forest combined with Cox regression model was performed for a prognostic model, based on which a nomogram was developed. Functional enrichment analysis and Spearman correlation analysis were also conducted to explore underlying mechanisms. The expression of some switch-involved AS events along with parent genes was verified by qRT-PCR with 20 pairs of normal and LUSC tissues. RESULTS: We found 16 pairs of splicing events from same parent genes which were strongly related to the splicing switch (intrapair correlation coefficient = - 1). Next, we built a reliable LNM classifier based on 13 AS events as well as a nice prognostic model, in which switched AS events behaved prominently. The qRT-PCR presented consistent results with previous bioinformatics analysis, and some AS events like ITIH5-10715-AT and QKI-78404-AT showed remarkable detection efficiency for LUSC. CONCLUSION: AS events, especially switched ones from the same parent genes, could provide new insights into the molecular diagnosis and therapeutic drug design of LUSC.
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Macleaya cordata extracts (MCE) are listed as feed additives in animal production by the European Food Authority. The core components of MCE are mainly sanguinarine (SA) and chelerythrine (CHE). This study aims to investigate sex differences in the pharmacokinetics and tissue residues of MCE in rats.Male and female rates were intragastrically administered MCE (1.25 mg·kg-1 body weight and 12.5 mg·kg-1 body weight dose for 28 days). SA and CHE concentrations were determined using high-performance liquid chromatography/tandem mass spectrometry.The peak plasma concentration (Cmax) and area under the curve (AUC) of both CHE and SA were higher in female than in male rats (12.5 mg·kg-1 body weight group), whereas their half-life (T1/2) and apparent volume of distribution (Vd) was lower (p < 0.05). Tissue rfesidue analysis indicated that SA and CHE were more distributed in male than in female rats and were highly distributed in the caecum and liver. SA and CHE were completely eliminated from the liver, kidney, lung, heart, spleen, leg muscle, and caecum after 120 h, indicating they did not accumulate in rats for a long time.Overall, we found that the pharmacokinetics and tissue residues of SA and CHE of male and female rats showed sex differences.
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Papaveraceae , Caracteres Sexuais , Animais , Cromatografia Líquida de Alta Pressão , Feminino , Masculino , Espectrometria de Massas , Papaveraceae/química , Extratos Vegetais , RatosRESUMO
Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers, and long noncoding RNAs (lncRNAs) regulate gene expression or activities. This study investigated the role of lncRNA LINC00551 in ESCC development and progression. Three paired ESCC and normal tissues were subjected to next-generation sequencing and we identified 82 upregulated and 60 downregulated lncRNAs, including LINC00551, which was confirmed to markedly downregulated in 78 ESCC tissues and in the Gene Expression Profiling Interactive Analysis data set. Downregulated LINC00551 expression was associated with lymph node metastasis, advanced TNM stage, and tumor size. Moreover, downregulated LINC00551 expression was also associated with poor progression-free survival and overall survival of ESCC patients. In vitro and in vivo, LINC00551 overexpression inhibited ESCC cell proliferation and invasion, whereas knockdown of LINC00551 expression promoted ESCC cell proliferation and invasion. RNA pull-down and mass spectrometry assays identified the potential LINC00551 binding proteins, and HSP27 was a promising LINC00551 targeting proteins after RNA immunoprecipitation assay. At the protein level, LINC00551 bound to and decreased HSP27 phosphorylation, and in turn, downregulated ESCC cell proliferation and invasion. The current study demonstrated the functional significance of LINC00551 in ESCC development, progression, and prognosis. Further study will assess LINC00551 as a novel prognostic marker or therapeutic target for ESCC.
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Proliferação de Células/genética , Carcinoma de Células Escamosas do Esôfago/genética , Proteínas de Choque Térmico/genética , Chaperonas Moleculares/genética , RNA Longo não Codificante/genética , Idoso , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Xenoenxertos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Fosforilação/genética , Prognóstico , RNA Longo não Codificante/antagonistas & inibidoresRESUMO
A series of natural, environmentally friendly and low-cost menthol-based hydrophobic deep eutectic solvents (DES) were synthesized to extract and concentrate solutes from dilute aqueous solutions, especially triphenylmethane (TPM) dye micropollutants. The system has excellent extraction performance for TPM. Density functional theory (DFT) and molecular dynamics (MD) simulation were used to quantitatively analyze the effect of the DES composition and TPM structure on the distribution of target molecules in two phases. The solvation free energy of ethyl violet (EV) in DES (-17.128 to -21.681 kcal mol-1) is much larger than that in water (-0.411 kcal mol-1), and increases with the increase of the HBD chain length, which is proportional to the extraction rate, indicating that the TPM molecules are more inclined to the DES environment, especially long-chain DES, than aqueous solution. For the same C12DES, the extraction efficiency of the TPM dyes follows the order: ethyl violet (EV) (99.9%) > crystal violet (CV) (99.6%) > methyl violet (MV) (98.8%). EV has the smallest positive charge and the smallest dipole moment (9.109 D), and the Flory-Huggins parameters of EV (χEV-C12DES 0.053) relative to MV and CV are the smallest in C12DES, and are also the largest in water (χEV-H2O 0.053), indicating that EV has the largest polarity difference with H2O and is more easily detached from water and compatible with the long-chain DES phase. The motion of EV and MV on the phase interface of DES and water was calculated to further analyze from the molecular level. At the same time, EV tends to move into the DES phase. In summary, the excellent extraction ability of DES for TPM is verified through experiments and simulations, providing solid theoretical support in terms of separation in other fields.
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Due to the extensive use of chemical insecticides, the field populations of Rhopalosiphum padi, a serious wheat pest worldwide, have developed resistance to insecticides. Therefore, deep understanding of the mechanisms of the aphid's physiological response to insecticides would be of importance for the management of insecticide resistance in pests. Takeout belongs to a protein superfamily found exclusively in insects. Previous research showed that the takeout gene had various functions in insect physiology and behavior. However, few studies have explored the functions of takeout in insect insecticide susceptibility. The susceptibility of R. padi to imidacloprid and beta-cypermethrin was tested. Thirteen takeout-like genes were identified based on the genome database of R. padi. The number of exons was variable in these takeout-like genes, and nine highly conserved amino acids (two Cysteine, two Proline, four Glycine and one Aspartic acid) were identified. Expression levels of takeout-like-2, takeout-like-3, takeout-like-5, takeout-like-8, takeout-like-10 and takeout-like-11 were significantly increased after imidacloprid treatment; seven genes (takeout-like-1, takeout-like-2, takeout-like-5, takeout-like-6, takeout-like-7, takeout-like-8 and takeout-like-11) tended to be upregulated after beta-cypermethrin treatment. RNA interference results showed that the mortalities of R. padi injected with dsTOL-2, dsTOL-5, dsTOL-8, dsTOL-10 and dsTOL-11 were significantly increased after exposure to imidacloprid in comparison with control (injection of dsGFP). Under two sublethal concentrations of beta-cypermethrin, the silencing of takeout-like-2, takeout-like-5 and takeout-like-11 significantly increased the mortalities of R. padi. These results provide evidence for the involvement of takeout-like genes in insecticide susceptibility of R. padi, which improves our understanding the determinant of insecticide susceptibility.
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Afídeos , Inseticidas , Animais , Afídeos/genética , Resistência a Inseticidas/genética , Inseticidas/toxicidade , TriticumRESUMO
Cations are crucial components in emerging functional polyelectrolytes for a myriad of applications. Rapid development in this area necessitates the exploration of new cations with advanced properties. Herein we describe a combination of computational and experimental design of cobaltocene metallo-cations that have distinct electronic and redox properties. One of the direct outcomes on the first synthesis of a complete set of cation derivatives is to discover highly stable cations, which are further integrated to construct metallo-polyelectrolytes as anion-exchange membranes in solid-state alkaline fuel cells. The device performance of these polyelectrolytes under highly basic and oxidative environments is competitive with many organo-polyelectrolytes.
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BACKGROUND: Alternative splicing (AS) plays critical roles in generating protein diversity and complexity. Dysregulation of AS underlies the initiation and progression of tumors. Machine learning approaches have emerged as efficient tools to identify promising biomarkers. It is meaningful to explore pivotal AS events (ASEs) to deepen understanding and improve prognostic assessments of lung adenocarcinoma (LUAD) via machine learning algorithms. METHOD: RNA sequencing data and AS data were extracted from The Cancer Genome Atlas (TCGA) database and TCGA SpliceSeq database. Using several machine learning methods, we identified 24 pairs of LUAD-related ASEs implicated in splicing switches and a random forest-based classifiers for identifying lymph node metastasis (LNM) consisting of 12 ASEs. Furthermore, we identified key prognosis-related ASEs and established a 16-ASE-based prognostic model to predict overall survival for LUAD patients using Cox regression model, random survival forest analysis, and forward selection model. Bioinformatics analyses were also applied to identify underlying mechanisms and associated upstream splicing factors (SFs). RESULTS: Each pair of ASEs was spliced from the same parent gene, and exhibited perfect inverse intrapair correlation (correlation coefficient = - 1). The 12-ASE-based classifier showed robust ability to evaluate LNM status of LUAD patients with the area under the receiver operating characteristic (ROC) curve (AUC) more than 0.7 in fivefold cross-validation. The prognostic model performed well at 1, 3, 5, and 10 years in both the training cohort and internal test cohort. Univariate and multivariate Cox regression indicated the prognostic model could be used as an independent prognostic factor for patients with LUAD. Further analysis revealed correlations between the prognostic model and American Joint Committee on Cancer stage, T stage, N stage, and living status. The splicing network constructed of survival-related SFs and ASEs depicts regulatory relationships between them. CONCLUSION: In summary, our study provides insight into LUAD researches and managements based on these AS biomarkers.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/genética , Processamento Alternativo/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Aprendizado de Máquina , PrognósticoRESUMO
BACKGROUND AND OBJECTIVES: It is unclear whether the prognostic significance of the 8th American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging system for non-small-cell lung cancer (NSCLC) is applicable to lung cancer as a second primary malignancy (LCSPM). This study used a population-based database to evaluate this relationship. METHODS: Patients diagnosed with second primary lung cancer after a nonpulmonary malignancy were identified from the Surveillance, Epidemiology and End Results (SEER) registry from 2004 to 2015. Cumulative incidence function (CIF) and multivariable CIF regression analyses were performed to estimate the difference in disease-specific mortality (DSM) among different TNM stages. RESULTS: Our cohort included 2687 patients from the SEER database. After CIF analysis, although rates of 1-year, 3-year, and 5-year DSM trended higher with increasing TNM stages, the DSM curves overlapped for many subcategories. In a multivariable regression analysis, hazards ratios (HRs) for subcategories of stage Ι demonstrated no significant difference compared with the reference stage ΙA1 ([ΙA2 HR = 1.120; 95% confidence interval [CI], 0.477-2.626]; [ΙA3 HR = 1.762; 95% CI, 0.752-4.126]; [ΙB HR = 2.003; 95% CI, 0.804-4.911]). The following HRs trended higher for increasing TNM stages but with overlapping CIs among adjacent stage groupings. CONCLUSION: The 8th edition AJCC TNM staging system fails to provide accurate prognostic value for LCSPM.
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Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Segunda Neoplasia Primária/patologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Incidência , Neoplasias Pulmonares/mortalidade , Masculino , Estadiamento de Neoplasias , Segunda Neoplasia Primária/mortalidade , Prognóstico , Análise de Regressão , Programa de SEER , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Bronchoscopy is applied broadly in the diagnosis and treatment of pulmonary diseases. Over the past few decades, an increasing number of studies about bronchoscopy have been published. However, little is known about their qualities and characteristics. METHODS: All of the databases in Web of Science (including the Web of Science Core Collection, BIOSIS Citation Index, KCI-Korean Journal Database, MEDLINE, Russian Science Citation Index, and SciELO Citation Index) were utilized to identify articles published from 1990 to 2020. The top 100 most cited articles about bronchoscopy were selected for degree centrality analysis and analyses regarding publication time, total citation number, the citation density, time-related flux, first author, published journal, geographic origin, and research theme. RESULTS: The selected articles were published mainly in the 2000s and 1990s. Citations per article ranged from 731 to 196. The leading country was the USA, followed by the United Kingdom. The most frequently studied themes were bronchoalveolar lavage (BAL) fluid and biopsy. The degree centrality analysis connoted that "BAL, inflammation, diagnosis" had a high degree of centrality in the 1990s, while "diagnosis, BAL, biopsy, prospective" took centre stage in the 2000s. CONCLUSIONS: The time, area, and theme distribution of the 100 most cited articles on bronchoscopy have been thoroughly analyzed. It is noticeable that researches based on BAL and endobronchial or transbronchial biopsies currently plays a major role.
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Bibliometria , Broncoscopia/métodos , Bases de Dados Factuais , Publicações Periódicas como Assunto , Humanos , InternacionalidadeRESUMO
Keyin Pills is a kind of traditional Chinese medicine for the treatment of psoriasis, but it has been reported that it can cause serious liver injury. In this paper, we used the integrated evidence chain method to retrieve and reevaluate the adverse drug reaction database, CNKI literature and cases of liver injury relating to Keyin Pills in specialist hepatology hospitals. We screened out 23 cases with the causal relationship of the possible grade and above. Among them, 11 cases showed the positive causal relationship only with Keyin Pills, accounting for 47.83%, suggesting that there was objective liver injury caused by Keyin Pills. The incubation period of liver injury caused by Keyin Pills is 1-90 days, and the cumulative dosage span is 20-1 800 g. There were obvious individual diffe-rences. There was no relationship between liver injury as well as dose and course of treatment, suggesting that Keyin Pills could induce immune idiosyncratic liver injury. Furthermore, based on the liver injury model induced by immunological stress, it was confirmed that Keyin Pills could induce acute liver injury in a dose-dependent manner in rats with immunological stress. The toxic dose(14 g·kg~(-1)) of a single dose was 6.7 times of the clinical equivalent dose, and had no significant effect on the biochemical index of liver function and histopathology in normal rats. Decomposition experiments showed that Dictamnus dasycarpus in Keyin Pills is the main medicinal flavor that causes special liver injury, and the other three medicines had neither liver injury nor compatibility attenuation effect. The results suggest that clinical medication shall pay attention to the risk of liver injury caused by Keyin Pills in patients with immunological stress.
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Doença Hepática Induzida por Substâncias e Drogas , Dictamnus , Medicamentos de Ervas Chinesas , Psoríase , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Fígado , Medicina Tradicional Chinesa , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , RatosRESUMO
OBJECTIVE: This study aimed to investigate the function and mechanism of neddylation of HDAC1 underlying drug resistance of AML cells. METHODS: Evaluation experiments of effects of HDAC1 on drug resistance of AML cells were performed with AML cell transfected with constructs overexpressing HDAC1 or multi-drug resistance AML cells transfected with siRNA for HDAC1 through observing cell viability, percentage of apoptotic cell, doxorubicin-releasing index and multidrug resistance associated protein 1 (MRP1) expression. Neddylation or ubiquitination of HDAC1 was determined by immunoprecipitation or Ni2+ pull down assay followed by western blot. The role of HDAC1 was in vivo confirmed by xenograft in mice. RESULTS: HDAC1 was significantly upregulated in refractory AML patients, and in drug-resistant AML cells (HL-60/ADM and K562/A02). Intracellular HDAC1 expression promoted doxorubicin resistance of HL-60, K562, and primary bone marrow cells (BMCs) of remission AML patients as shown by increasing cell viability and doxorubicin-releasing index, inhibiting cell apoptosis. Moreover, HDAC1 protein level in AML cells was regulated by the Nedd8-mediated neddylation and ubiquitination, which further promoted HDAC1 degradation. In vivo, HDAC1 overexpression significantly increased doxorubicin resistance; while HDACs inhibitor Panobinostat markedly improved the inhibitory effect of doxorubicin on tumor growth. Furthermore, HDAC1 silencing by Panobinostat and/or lentivirus mediated RNA interference against HDAC1 effectively reduced doxorubicin resistance, resulting in the inhibition of tumor growth in AML bearing mice. CONCLUSION: Our findings suggested that HDAC1 contributed to the multidrug resistance of AML and its function turnover was regulated, at least in part, by post-translational modifications, including neddylation and ubiquitination.
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Resistencia a Medicamentos Antineoplásicos , Histona Desacetilase 1/biossíntese , Histona Desacetilase 1/metabolismo , Leucemia Mieloide Aguda/patologia , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Indução Enzimática/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Histona Desacetilase 1/deficiência , Histona Desacetilase 1/genética , Humanos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Camundongos , Pessoa de Meia-Idade , Proteína NEDD8/metabolismo , Ubiquitinação/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto JovemRESUMO
Efficient and durable nonprecious metal electrocatalysts for the oxygen reduction (ORR) are highly desirable for several electrochemical devices, including anion exchange membrane fuel cells (AEMFCs). Here, a 2D planar electrocatalyst with CoOx embedded in nitrogen-doped graphitic carbon (N-C-CoOx ) was created through the direct pyrolysis of a metal-organic complex with a NaCl template. The N-C-CoOx catalyst showed high ORR activity, indicated by excellent half-wave (0.84â V vs. RHE) and onset (1.01â V vs. RHE) potentials. This high intrinsic activity was also observed in operating AEMFCs where the kinetic current was 100â mA cm-2 at 0.85â V. When paired with a radiation-grafted ETFE powder ionomer, the N-C-CoOx AEMFC cathode was able to achieve extremely high peak power density (1.05â W cm-2 ) and mass transport limited current (3â A cm-2 ) for a precious metal free electrode. The N-C-CoOx cathode also showed good stability over 100â hours of operation with a voltage decay of only 15 % at 600â mA cm-2 under H2 /air (CO2 -free) reacting gas feeds. The N-C-CoOx cathode catalyst was also paired with a very low loading PtRu/C anode catalyst, to create AEMFCs with a total PGM loading of only 0.10â mgPt-Ru cm-2 capable of achieving 7.4â W mg-1 PGM as well as supporting a current of 0.7â A cm-2 at 0.6â V with H2 /air (CO2 free)-creating a cell that was able to meet the 2019 U.S. Department of Energy initial performance target of 0.6â V at 0.6â A cm-2 under H2 /air with a PGM loading <0.125â mg cm-2 with AEMFCs for the first time.
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BACKGROUND: Induction chemotherapy has been shown to improve survival of patients with stage III A/N2 (T1-3, N2, M0) non-small cell lung cancer (NSCLC), followed by resection, but the benefits of neoadjuvant radiotherapy still remain controversial. METHODS: PubMed, Embase, and Cochrane library databases were searched for relevant randomized controlled trials (RCTs) comparing the outcomes of induction chemoradiotherapy over induction chemotherapy, in patients with resectable stage IIIA/N2 NSCLC. Odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were calculated using random- or fixed-effects model, and heterogeneity was assessed using I2 test. Publication bias was examined by funnel plots analysis. RESULTS: A total of three RCTs met the inclusion criteria of our meta-analysis. The pooled results demonstrated that, in comparison to induction chemotherapy, induction chemoradiotherapy has a significant benefit in tumor response, mediastinal downstaging, and pathological complete response of mediastinal lymph nodes. In addition, no more peri-intervention mortality was detected in patients from chemoradiotherapy group, and a higher number of patients from this group had R0 resection. However, our results did not show any difference between overall survival and progression-free survival after 2, 4, and 6 years of follow-ups, in patients undergoing radiation therapy vs. induction chemotherapy. CONCLUSION: Preoperative chemoradiotherapy, as compared to induction chemotherapy alone, is associated with similar peri-intervention mortality, a greater tumor response, mediastinal nodule downstaging, and rate of R0 resection, but does not improve survival of resectable stage IIIA/N2 NSCLC patients.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/mortalidade , Quimioterapia de Indução/mortalidade , Neoplasias Pulmonares/terapia , Terapia Neoadjuvante/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Taxa de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: To explore the risk factors, preventive measures and therapeutic methods for bronchopleural fistula (BPF) after lung resections.â© Methods: A restrospective analysis for 11 patients with BPF after pneumonectomy from April 2012 to June 2016 in Department of Thoracic Surgery, Xiangya Hospital, Central South University was performed. Their clinical characteristics, treatment and prognosis were analyzed, and the risk factors and effective therapeutic strategies were summarized.â© Results: Among the 11 patients with BPF, 10 cases were cured finally, and 1 case with conservative treatment was dead. The total mortality rate was 9.09%. The 10 patients treated with positive measures were all cured, including 5 cases with pulmonary lobectomy and pneumonectomy, 4 cases with amplatzer and covered stent, and 1 case with fibrin glue. One case with conservative treatment was dead because of respiratory failure.â© Conclusion: It is important to intervene BPF as early as possible. Fibrin glue via bronchoscope for tiny BPF after lung resection is preferred to be considered. We recommend to take early positive operation (pulmonary lobectomy and pneumonectomy) after pulmonary resection if the BPF cannot be cured via bronchoscope whereas the patients' condition is allowed. The amplatzer or covered stent should be considered first for the patient with BPF after pneumonectomy.