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1.
Pestic Biochem Physiol ; 165: 104563, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32359542

RESUMO

Bradysia odoriphaga is a destructive insect pest, damaging more than 30 crop species. Nicotinic acetylcholine receptors (nAChRs) mediating fast excitatory transmission in the central nervous system in insects are the molecular targets of some economically important insecticides including imidacloprid, which has been widely used to control B. odoriphaga in China since 2013. However, the clear characterization about nAChRs in B. odoriphaga is still unknown. Hence, our objective is to identify and characterize the nAChR gene family in B. odoriphaga based on the transcriptome database and sequence, phylogenetic and expression profiles analysis. In this study, we cloned seven nAChR subunit genes from B. odoriphaga, including Boα1, Boα2, Boα3, Boα7, Boα8, Boß1 and Boß3. Sequence analysis revealed that the seven nAChR subunits of B. odoriphaga shared the typical structural features with Drosophila melanogaster nAChR α1 subunit, including an extracellular N-terminal domain containing six functional loops (loop A-F), a signature Cys-loop with two disulfide bond-forming cysteines separated by 13 amino acid residues, and four typical transmembrane helices (TM1-TM4) in the C-terminal region. Phylogenetic analysis suggested that seven nAChR subunit genes in B. odoriphaga are evolutionarily conserved among four model insects, including D. melanogaster, Bombyx mori, Apis mellifera and Tribolium castaneum. Meanwhile, nAChR α4, α5, α6 and ß2 subunit genes may potentially exist in B. odoriphaga, which need further study. Furthermore, quantitative real-time PCR analysis revealed the specific expression pattern of nAChR subunits in three body parts including head, thorax and abdomen, and developmental expression pattern of nAChR subunits throughout the B. odoriphaga life cycle. These results provided necessary information for further investigating the diverse functions of nAChRs in B. odoriphaga.


Assuntos
Drosophila melanogaster , Receptores Nicotínicos , Sequência de Aminoácidos , Animais , Abelhas , China , Filogenia
2.
Mol Plant Pathol ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32394633

RESUMO

bsr-d1, an allele encoding a transcription factor identified from the rice cultivar Digu, confers durable, broad-spectrum resistance to infections by strains of Magnaporthe oryzae. bsr-d1 was predicted to inhibit M. oryzae-induced expression of Bsr-d1 RNA and degradation of hydrogen peroxide to achieve resistance to M. oryzae. However, the global effect of biological process and molecular function on blast resistance mediated by Bsr-d1 remains unknown. In this study, we compared transcriptomic profiling between Bsr-d1 knockout (Bsr-d1KO) lines and the wild type, TP309. Our study revealed that bsr-d1 mainly regulates the redox state of plant cells, but also affects amino acid and unsaturated fatty acid metabolism. We further found that BSR-D1 indirectly regulates salicylic acid biosynthesis, metabolism, and signal transduction downstream of the activation of H2 O2 signalling in the bsr-d1-mediated immune response. Furthermore, we identified a novel peroxidase-encoding gene, Perox3, as a new BSR-D1 target gene that reduces resistance to M. oryzae when overexpressed in TP309. These results provide new insights into the bsr-d1-mediated blast resistance.

3.
Pestic Biochem Physiol ; 166: 104565, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32448419

RESUMO

Uridine diphosphate (UDP)-glycosyltransferases (UGTs) catalyze the conjugation of small lipophilic endogenous and exogenous compounds with sugars to produce water-soluble glycosides, playing an important role in insect endobiotic regulation and xenobiotic detoxification. In this study, two UGT-inhibitors, sulfinpyrazone and 5-nitrouracil, significantly increased spirotetramat toxicity against third instar nymphs of resistant Aphis gossypii, whereas there were no synergistic effects in apterous adult aphids, suggesting UGT involvement in spirotetramat resistance in cotton aphids. Furthermore, the UHPLC-MS/MS was employed to determine the content of spirotetramat and its four metabolites (S-enol, S-glu, S-mono, S-keto) in the honeydew of resistant cotton aphids under spirotetramat treatment. No residual spirotetramat was detected in the honeydew, while its four metabolites were detected at a S-enol: S-glu: S-mono: S-keto ratio of 69.30: 6.54: 1.44: 1.00. Therefore, glycoxidation plays a major role in spirotetramat inactivation and excretion in resistant aphids. Compared with the susceptible strain, the transcriptional levels of UGT344M2 were significantly upregulated in nymphs and adults of the resistant strain. RNA interference of UGT344M2 dramatically increased spirotetramat toxicity in nymphs, but no such effect were found in the resistant adult aphids. Overall, UGT-mediated glycoxidation were found to be involved in spirotetramat resistance. The suppression of UGT344M2 significantly increased the sensitivity of resistant nymphs to spirotetramat, suggesting that UGT344M2 upregulation might be associated with spirotetramat detoxification. This study provides an overview of the involvement of metabolic factors, UGTs, in the development of spirotetramat resistance.


Assuntos
Afídeos , Inseticidas , Animais , Compostos Aza , Glicosiltransferases , Resistência a Inseticidas , Compostos de Espiro , Espectrometria de Massas em Tandem , Difosfato de Uridina
4.
New Phytol ; 226(6): 1850-1863, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32112568

RESUMO

Broad-spectrum resistance is highly preferred in crop breeding programmes. Previously, we have reported the identification of the broad-spectrum resistance-Digu 1 (bsr-d1) allele from rice Digu. The bsr-d1 allele prevents activation of Bsr-d1 expression by Magnaporthe oryzae infection and degradation of H2 O2 by peroxidases, leading to resistance to M. oryzae. However, it remains unknown whether defence pathways other than H2 O2 burst and peroxidases contribute to the bsr-d1-mediated immunity. Blast resistance was determined in rice leaves by spray and punch inoculations. Target genes of OsMYB30 were identified by one-hybrid assays in yeast and electrophoretic mobility shift assay. Lignin content was measured by phloroglucinol-HCl staining, and acetyl bromide and thioacidolysis methods. Here, we report the involvement of the OsMYB30 gene in bsr-d1-mediated blast resistance. Expression of OsMYB30 was induced during M. oryzae infection or when Bsr-d1 was knocked out or downregulated, as occurs in bsr-d1 plants upon infection. We further found that OsMYB30 bound to and activated the promoters of 4-coumarate:coenzyme A ligase genes (Os4CL3 and Os4CL5) resulting in accumulation of lignin subunits G and S. This action led to obvious thickening of sclerenchyma cells near the epidermis, inhibiting M. oryzae penetration at the early stage of infection. Our study revealed novel components required for bsr-d1-mediated resistance and penetration-dependent immunity, and advanced our understanding of broad-spectrum disease resistance.

5.
Environ Sci Pollut Res Int ; 27(15): 18743-18756, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32207002

RESUMO

A novel combined bioreactor integrating anaerobic baffling and anaerobic filtration process was developed and operated for 210 days to treat low-strength rural wastewater. The effects of hydraulic residence time (HRT) and organic loading rate (OLR) on chemical oxygen demand (COD) removal and methane (CH4) production of the combined bioreactor were investigated. The combined bioreactor can start up successfully in 25 days and achieve enhanced performance. The COD removal rate and CH4 yield were influenced significantly by HRT and OLR. The influent COD was removed effectively through the synergistic effects of the anaerobic baffling and anaerobic filtration. The baffle zone played the main role in the degradation of the pollutants, and the filter zone mainly contributed to improve the resistance to shock loading. High-throughput sequencing technology was used to analyze the bacterial and archaeal community structure and diversity. Clostridium_sensu_stricto, Longilinea, Acetoanaerobium, Arcobacter, and Acinetobacter were found to be the dominant bacteria. While Methanothrix and Methanoregula were the dominant archaea, which were responsible for methane generation. This study not only highlights the good energy recovery and resource utilization potential of the combined bioreactor but also presents significant guidance for the application of the combined anaerobic process for low-strength rural wastewater treatment.

6.
Toxicology ; 435: 152410, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32068018

RESUMO

Epidemiologic studies show that the levels of air pollutants and particulate matter are positively associated with the morbidity and mortality of cardiovascular diseases. Here we demonstrate that the intratracheal instillation of multi-walled carbon nanotubes (MWCNTs), a standard fine particle, exacerbate doxorubicin (DOX)-induced cardiotoxicity in mice through altering gut microbiota and pulmonary and colonic macrophage phenotype. MWCNTs (25 µg/kg per day, 5 days a week for 3 weeks) promoted cardiotoxicity and apoptosis in the DOX (2 mg/kg, twice a week for 5 weeks)-treated C57BL/6 mice. MWCNTs exaggerated DOX-induced gut microbiota dysbiosis characterized by the increased abundances of Helicobacteraceae and Coriobacteriaceae. In addition, MWCNTs promoted DOX-induced M1-like polarization of colonic macrophages with an increase in TNF-α, IL-1ß and CC chemokine ligand 2 in peripheral blood. Importantly, treatment with the antibiotics attenuated MWCNTs plus DOX-induced apoptosis of cardiomyocytes and M1-like polarization of colonic macrophages. The fecal microbiota transplantation demonstrated that MWCNTs exaggerated DOX-induced cardiotoxicity with M1-like polarization of colonic macrophages. The conditioned medium from MWCNTs-treated pulmonary macrophages promoted DOX-induced gut microbiota dysbiosis and colonic macrophage polarization. Furthermore, the co-culture of macrophages and fecal bacteria promoted M1-like macrophage polarization and their production of TNF-α and IL-1ß, and thereby exacerbated the effects of MWCNTs. Moreover, IL-1ß and TNF-α blockade, either alone or in combination attenuated MWCNTs-exacerbated cardiotoxicity. In summary, MWCNTs exacerbate DOX-induced cardiotoxicity in mice through gut microbiota and pulmonary and colonic macrophage interaction. Our findings identify a novel mechanism of action of inhaled particle-driven cardiotoxicity.

7.
Mol Cancer ; 19(1): 41, 2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-32103760

RESUMO

BACKGROUND: The poor prognosis of esophageal squamous cell carcinoma (ESCC) highlights the need for novel strategies against this disease. Our previous study suggested the involvement of CCL2 and tumor associated macrophages (TAMs) in esophageal carcinogenesis. Despite the recognition of TAMs as a promising target for cancer treatment, mechanisms underlying its infiltration, activation and tumor-promotive function in ESCC remain unknown. METHODS: Human esophageal tissue array and TCGA database were used to evaluate the clinical relevance of CCL2 and TAMs in ESCC. F344 rats and C57BL/6 mice were treated with N-nitrosomethylbenzylamine (NMBA) to establish orthotopic models of esophageal carcinogenesis. CCL2/CCR2 gene knockout mice and macrophage-specific PPARG gene knockout mice were respectively used to investigate the role of infiltration and polarization of TAMs in ESCC. CCL2-mediated monocyte chemotaxis was estimated in malignantly transformed Het-1A cells. THP-1 cells were used to simulate TAMs polarization in vitro. RNA-sequencing was performed to uncover the mechanism. RESULTS: Increasing expression of CCL2 correlated with TAMs accumulation in esophageal carcinogenesis, and they both predicts poor prognosis in ESCC cohort. Animal studies show blockade of CCL2-CCR2 axis strongly reduces tumor incidence by hindering TAMs recruitment and thereby potentiates the antitumor efficacy of CD8+ T cells in the tumor microenvironment. More importantly, M2 polarization increases PD-L2 expression in TAMs, resulting in immune evasion and tumor promotion through PD-1 signaling pathway. CONCLUSION: This study highlights the role of CCL2-CCR2 axis in esophageal carcinogenesis. Our findings provide new insight into the mechanism of immune evasion mediated by TAMs in ESCC, suggesting the potential of TAMs-targeted strategies for ESCC prevention and immunotherapy.

8.
Pest Manag Sci ; 76(4): 1371-1377, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31605421

RESUMO

BACKGROUND: The cotton aphid Aphis gossypii Glover is one of the most destructive insect pests. It has evolved resistance to numerous insecticides around the world due to the application of insecticides. Uridine diphosphate (UDP)-glycosyltransferases (UGTs) have been reported to potentially facilitate the detoxification process of imidacloprid and thiamethoxam in A. gossypii. RESULTS: In this study, the field populations of A. gossypii developed different levels of resistance to multiple insecticides. A UGT inhibitor, 5-nitrouracil, dramatically increased the toxicity of acetamiprid in resistant populations, moderately increased the toxicity of sulfoxaflor in the imidacloprid susceptible (IMI_S) population, and populations from Yuncheng in Shanxi Province (SXYC) and Jingzhou in Hubei Province (HBJZ), and increased the toxicity of bifenthrin in the IMI_S and HBJZ populations, but there was no synergism on omethoate or carbosulfan. Quantitative real-time PCR analysis revealed that UGT344B4 and UGT344C7 were overexpressed in all field populations, and UGT344N4 was overexpressed in the SDBZ and HBZJ populations. Furthermore, the suppression of UGT344B4 or UGT344C7 by RNA interference significantly increased the susceptibility to bifenthrin in the IMI_S population and the susceptibility to sulfoxaflor in the SXYC population. CONCLUSION: These results suggested that UGTs are potentially involved in the detoxification of neonicotinoid, sulfoximine, and pyrethroid insecticides in A. gossypii. Furthermore, the overexpression of UGTs could be associated with insecticide resistance in field populations of A. gossypii. The results might be helpful for the management of insecticide resistance in field populations of A. gossypii. © 2019 Society of Chemical Industry.

9.
Plant Sci ; 290: 110295, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31779907

RESUMO

Among the phosphofructokinase B-type carbohydrate kinase (PCK) family proteins, only few proteins, like the FRUCTOKINASE-LIKE 1 and 2, have been functionally characterized in regulation of chloroplast development. Here, we report the involvement of a PCK protein PFKB1 in chloroplast development by identification of a new rice mutant, revertible early yellowing Kitaake 2 [rey(k2)]. The mutant rey(k2) shows yellow leaf phenotype, reduced photosynthetic pigments, and retarded chloroplast development during early stages of seedlings, but gradually recovered at later stages. The phenotype of rey(k2) is resulted from the disruption of the PFKB1 protein. The Pfkb1 gene is ubiquitously expressed, and its protein is mainly targeted to the chloroplast and, in some cells, to the nucleus. In addition, the PFKB1 protein possesses phosphofructokinase activity in vitro. The rey(k2) mutant affects RNA levels of chloroplast-associated genes. In particular, the nuclear-encoded RNA polymerase (NEP)-dependent genes are expressed at a sustained high level in rey(k2) even after turning green, indicating that PFKB1 is essential for suppressing the expression of NEP-dependent genes. Taken together, our study suggests that PFKB1 functions as a novel regulator indispensable for early chloroplast development, at least partly by regulating chloroplast-associated genes.


Assuntos
Cloroplastos/metabolismo , Oryza/genética , Proteínas de Plantas/genética , Cloroplastos/genética , Oryza/citologia , Oryza/crescimento & desenvolvimento , Proteínas de Plantas/metabolismo , Plântula/citologia , Plântula/genética , Plântula/crescimento & desenvolvimento
10.
Environ Sci Pollut Res Int ; 27(7): 6785-6795, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31873905

RESUMO

A submerged anaerobic membrane bioreactor (SAnMBR) was used to treat low-concentration domestic sewage. The effects of hydraulic retention time (HRT) and organic load (OLR) on chemical oxygen demand (COD) removal, methanogenesis, and membrane fouling of the system were investigated. The SAnMBR achieved good COD removal efficiency as well as stable methane production, which were significantly affected by both OLR and HRT. The influent dissolved organic matter (DOM) was decomposed and transformed over time, and DOM concentration was gradually reduced. It can be inferred that the SAnMBR can effectively intercept the production of extracellular polymeric substances and improve effluent quality. The phenomenon of membrane fouling was investigated using various analytical tools. Results demonstrated that the SAnMBR was achieved good transmembrane pressures (TMP) (10-15 kPa), and the hydraulic force generated by the stirring device has a dynamic physical shearing action on the surface of the membrane, which can partly alleviate membrane fouling.


Assuntos
Esgotos , Eliminação de Resíduos Líquidos , Anaerobiose , Análise da Demanda Biológica de Oxigênio , Reatores Biológicos , Membranas Artificiais
11.
Arch Toxicol ; 93(11): 3261-3276, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31570982

RESUMO

Clinical application of doxorubicin (Dox) is limited due to its undesirable side effects, especially cardiotoxicity. Several microRNAs (miRNAs) such as microRNA-140-5p and miR-23a aggravate Dox-induced cardiotoxicity. Here we demonstrate that upregulation of miRNA let-7f-2-3p by long noncoding RNA (lncRNA) NEAT1 inhibits exportin-1 (XPO1)-mediated nuclear export of hematopoietic-substrate-1 associated protein X-1 (HAX-1) in Dox-induced cardiotoxicity. Treatment of the H9c2 cells with the Dox (1 µM) for 6 h inhibited HAX-1 nuclear export and decreased XPO1 expression. Overexpression of XPO1 significantly attenuated the Dox-induced leakage of myocardial enzymes (creatine phosphokinase, creatine kinase-MB and lactate dehydrogenase) and cardiomyocyte apoptosis with the increased HAX-1 nuclear export. Differentially expressed miRNAs including let-7f-2-3p were selected from the Dox or vehicle-treated cardiomyocytes. TargetScan and luciferase assay showed that let-7f-2-3p targeted XPO1 3' UTR. Inhibition of let-7f-2-3p reduced Dox-induced cardiotoxicity and apoptosis by inhibiting XPO1-mediated HAX-1 nuclear export, whereas let-7f-2-3p overexpression aggravated these effects. In addition, lncRNA NEAT1 was identified as an endogenous sponge RNA to repress let-7f-2-3p expression. Overexpression of lncRNA NEAT1 abolished the increased let-7f-2-3p expression by Dox, and thereby attenuated cardiotoxicity. The loss function of let-7f-2-3p increased XPO1-mediated HAX-1 nuclear export and reduced myocardial injury in Dox (20 mg/kg)-treated rats. Importantly, let-7f-2-3p inhibition in mice alleviated Dox-induced cardiotoxicity and preserved the antitumor efficacy. Together, let-7f-2-3p regulated by lncRNA NEAT1 aggravates Dox-induced cardiotoxicity through inhibiting XPO1-mediated HAX-1 nuclear export, and may serve as a potential therapeutic target against Dox-induced cardiotoxicity.

12.
Front Physiol ; 10: 1112, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31555146

RESUMO

Circular RNAs (circRNAs) have vital roles in great variety of biological processes. However, expression levels and functions of circRNAs related to heat acclimation (HA) are poorly understood. This study is the first time an in-depth circRNA expression profiling were used to investigate circRNA-miRNA interactions in HA rats in order to further comprehend the mechanisms underlying HA. CircRNA expression profile was performed in rats' hypothalamus of HA and control group with microarray assays and their functions were predicted by using Bioinformatics analysis. Differential circRNAs and their regulated downstream miRNAs and mRNAs were quantitatively validated by means of quantitative polymerase chain reaction in real-time (RT-qPCR). Enzyme-linked immunosorbent assay (ELISA) was then applied to predict the expression of proteins. In total, 53 circRNAs were expressed distinctively between the HA and Control; up- and down-regulation of circRNAs were 28 and 25, respectively, in HA (fold change > 1.5, P < 0.05). Three circRNAs and two miRNAs and three predicted mRNAs were obviously regulated after validated by RT-qPCR in HA rats. Two proteins expression were proportional to their mRNA changes. Further analysis demonstrates that circRNAs closest to HA can be categorized into three signal pathways: including rno_circRNA_014301-vs-rno-miR-3575-vs-Hif-1α, rno_circRNA_014301-vs-rno-miR-3575-vs-Lppr4, and rno_circRNA_010393-vs-rno-miR-20b-3p-vs-Mfap4 in hypoxia response pathways, substance/energy metabolism, and inflammatory response pathways. Our findings implicate that many circRNAs regulate expressions of genes that interact with each other to exert their functions during HA.

13.
Pestic Biochem Physiol ; 159: 98-106, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400791

RESUMO

The cotton aphid, Aphis gossypii Glover, is a destructive global crop pest. Control of A. gossypii has relied heavily on the application of chemical insecticides. The cotton aphid has developed resistance to numerous insecticides, including imidacloprid, which has been widely used to control cotton pests in China since the 1990s. Our objective was to investigate the potential role of UDP-glycosyltransferases (UGTs) in imidacloprid resistance based on transcriptomic and proteomic analyses of field-originated imidacloprid-resistant (IMI_R) and -susceptible (IMI_S) A. gossypii clones. The transcriptomic and proteomic analyses revealed that 12 out of 512 differentially expressed genes and three out of 510 differentially expressed proteins were predicted as UDP-glycosyltransferase (UGT). Based on quantitative real-time PCR analysis, nine UGT genes, UGT343A4, UGT344A15, UGT344A16, UGT344B4, UGT344C7, UGT344C9, UGT344N4, UGT 24541, and UGT7630, were up-regulated in the IMI_R clone compared to the IMI_S clone. Meanwhile, UGT344A16, UGT344B4, UGT344C7, and UGT344N4 were overexpressed at the protein level based on western blot analysis. Furthermore, knockdown of UGT344B4 or UGT344C7 using RNA interference (RNAi) significantly increased sensitivity to imidacloprid in the IMI_R clone. In conclusion, UGTs potentially contributed to imidacloprid resistance in A. gossypii originating from cotton-growing regions of China. These results provide insights into the way we study insecticide resistance in cotton aphids.


Assuntos
Afídeos/efeitos dos fármacos , Glucosiltransferases/metabolismo , Neonicotinoides/farmacologia , Nitrocompostos/farmacologia , Animais , Afídeos/genética , Afídeos/metabolismo , Glucosiltransferases/genética , Resistência a Inseticidas/genética , Proteômica , Transcriptoma/genética
14.
Curr Opin Plant Biol ; 50: 114-120, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31163394

RESUMO

Blast is arguably the most devastating fungal disease of rice. Systematic studies of this disease have made significant progress and identified many genes. Broad-spectrum resistance is highly preferred in agricultural practice. Here, we focus our discussion on resistance (R) and defense-regulator (DR) genes that confer broad-spectrum resistance to Magnaporthe oryzae, in particular those potentially causing no significant yield penalties. Recent advances show that broad-spectrum resistance can be achieved without significant yield penalties, or even with yield benefits. Cross talks of defense signaling mediated by these genes are present that may allow the host to integrate different anti-fungal factors against M. oryzae infection. We also summarize possible mechanisms underlying broad-spectrum resistance to rice blast.


Assuntos
Magnaporthe , Oryza , Resistência à Doença , Humanos , Doenças das Plantas
15.
Int J Mol Sci ; 20(11)2019 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-31181758

RESUMO

To protect themselves from pathogens, plants have developed an effective innate immune system. Plants recognize pathogens and then rapidly alter signaling pathways within individual cells in order to achieve an appropriate immune response, including the generation of reactive oxygen species, callose deposition, and transcriptional reprogramming. Post-translational modifications (PTMs) are versatile regulatory changes critical for plant immune response processes. Significantly, PTMs are involved in the crosstalk that serves as a fine-tuning mechanism to adjust cellular responses to pathogen infection. Here, we provide an overview of PTMs that mediate defense signaling perception, signal transduction in host cells, and downstream signal activation.


Assuntos
Imunidade Vegetal , Proteínas de Plantas/metabolismo , Processamento de Proteína Pós-Traducional , Transdução de Sinais
16.
Transl Lung Cancer Res ; 8(2): 124-134, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31106123

RESUMO

Background: Epidermal growth factor receptor (EGFR) mutation represents a good response to EGFR-tyrosine kinase inhibitor and an advantageous prognostic factor in advanced-stage non-small cell lung cancer (NSCLC). However, the predictive value of EGFR mutation for prognosis in NSCLC patients after complete surgery, which more reflective of natural process, remains controversial. We sought to examine the predictive value of EGFR mutation in NSCLC. Several studies with small sample sizes have been reported but small studies bring bias especially in a postoperative setting. Therefore, we sought to pool all current evidence to show the true effects. Methods: Electronic databases were used to search the relevant articles. Disease-free survival (DFS), which will be less effected by subsequent treatments after recurrence, was the primary endpoint. The DFS between EGFR mutated and wild-type patients were compared focus on stage I patients who are rarely received adjuvant therapy. Besides, the DFS of patients with 19 exon deletion (19del) and 21 exon L858R mutation (L858R) were compared. A random effects model was used. Results: A total of 19 relevant studies which involved 4,872 cases were enrolled and 2,086 patients were EGFR-mutated. The majority of studies used PCR-based methods to detect EGFR mutations. Through meta-analysis, we observed the DFS of EGFR-mutated patients were similar to wild type patients in overall population (HR 0.93, 95% CI: 0.74 to 1.17). Similar results were observed in stage I subgroup (HR 0.82, 95% CI: 0.50 to 1.33). DFS of 19 del patients were potentially inferior to L858R patients but the difference was not significant (HR 1.38, 95% CI: 0.76 to 2.52). Conclusions: There was no significant difference in postoperative DFS between EGFR-mutant patients and wild-type with resected NSCLC. In addition, there is still insufficient evidence to support different postoperative treatment strategies (especially for stage I) for both mutated and wild-type patients. However, 19 del may be a negative factor, which may require more strict management. Thus, we strongly encourage reporting specific prognostic impacts of different mutation types.

18.
Thorac Cancer ; 10(4): 593-600, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30854808

RESUMO

BACKGROUND: To date, few studies have evaluated the impact of lobectomy versus sublobar resection for early small cell lung cancer (SCLC). We investigated the survival rates of patients with pathological stage T1-2N0M0 SCLC who underwent lobectomy or sublobar resection. METHODS: We identified 548 SCLC patients in the Surveillance, Epidemiology, and End Results database who underwent lobectomy or sublobar resection. Propensity score matching (PSM) and Cox regression analysis were used to adjust for baseline characteristics. RESULTS: The three-year overall survival (OS) of patients treated with lobectomy (n = 376, 60%) was significantly higher than those treated with sublobar resection (n = 172, 38%). PSM and Cox multivariable analysis further confirmed this result (hazard ratio [HR] 0.543, 95% confidence interval [CI] 0.421-0.680; P < 0.001). The three-year OS of patients treated with segmentectomy (n = 24, 54%) and wedge resection (n = 148, 36%) was not significantly different (HR 0.639, 95% CI 0.393-1.039; P = 0.071). Based on PSM analysis, segmentectomy conferred a superior survival advantage to patients relative to wedge resection (HR 0.466, 95% CI 0.221-0.979; P = 0.040). CONCLUSION: Lobectomy correlated with superior survival. For patients in which lobectomy is unsuitable, prognosis following segmentectomy appears to be better than after wedge resection.

19.
Thorac Cancer ; 10(4): 823-831, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30779318

RESUMO

BACKGROUND: The clinical utility of malignant pleural effusion (MPE) to detect mutation has been well documented; however, routine practice of the use of MPE involves collection of the cell pellet to detect mutation, and limited studies have interrogated the MPE supernatant as an alternative source of tumor-derived DNA for mutation profiling. In this study, we investigated the potential of MPE supernatant as a liquid biopsy specimen by comparing its mutation profile with that of matched MPE cell pellets, tissue, and plasma samples. METHODS: Sequencing data from 17 patients with matched lung tissue, plasma, and MPE samples were retrospectively analyzed. Capture-based targeted sequencing was performed on matched plasma and MPE supernatant samples obtained from 154 patients with advanced lung adenocarcinoma. RESULTS: MPE supernatants had significantly higher median maximum allelic fractions (maxAFs) than their corresponding cell pellets (P = 0.008) and plasma samples (P = 0.036), and a comparable maxAF value to that of tissue samples (P = 0.675). Comparison of MPE supernatant and matched plasma samples from the larger cohort (n = 154) revealed a comparable mutation detection rate; however, MPE supernatant had a significantly higher median maxAF than plasma (20.3% vs. 1.13%; P < 0.001). Furthermore, the concordance rates between MPE supernatant and plasma for single-nucleotide and copy number variations were 56% and 18%, respectively, suggesting that MPE supernatant reveals a more comprehensive mutation spectrum, particularly for copy number variations. CONCLUSION: Overall, our study shows that MPE supernatant is an optimal alternative source of tumor-derived DNA for comprehensive mutation profiling.

20.
New Phytol ; 222(3): 1507-1522, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30632163

RESUMO

miRNAs contribute to plant resistance against pathogens. Previously, we found that the function of miR398b in immunity in rice differs from that in Arabidopsis. However, the underlying mechanisms are unclear. In this study, we characterized the mutants of miR398b target genes and demonstrated that multiple superoxide dismutase genes contribute to miR398b-regulated rice immunity against the blast fungus Magnaporthe oryzae. Out of the four target genes of miR398b, mutations in Cu/Zn-Superoxidase Dismutase1 (CSD1), CSD2 and Os11g09780 (Superoxide DismutaseX, SODX) led to enhanced resistance to M. oryzae and increased hydrogen peroxide (H2 O2 ) accumulation. By contrast, mutations in Copper Chaperone for Superoxide Dismutase (CCSD) resulted in enhanced susceptibility. Biochemical studies revealed that csd1, csd2 and sodx displayed altered expression of CSDs and other superoxide dismutase (SOD) family members, leading to increased total SOD enzyme activity that positively contributed to higher H2 O2 production. By contrast, the ccsd mutant showed CSD protein deletion, resulting in decreased CSD and total SOD enzyme activity. Our results demonstrate the roles of different SODs in miR398b-regulated resistance to rice blast disease, and uncover an integrative regulatory network in which miR398b boosts total SOD activity to upregulate H2 O2 concentration and thereby improve disease resistance.


Assuntos
Resistência à Doença , Peróxido de Hidrogênio/metabolismo , MicroRNAs/metabolismo , Oryza/metabolismo , Doenças das Plantas/microbiologia , Superóxido Dismutase/metabolismo , Regulação para Baixo , Regulação da Expressão Gênica de Plantas , Magnaporthe , MicroRNAs/genética , Modelos Biológicos , Mutação/genética , Oryza/genética , Oryza/microbiologia , Espécies Reativas de Oxigênio/metabolismo
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