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1.
Org Lett ; 22(3): 818-822, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31961159

RESUMO

A highly efficient asymmetric hydrogenation of γ- and δ-ketoacids was developed by using a chiral spiro iridium catalyst (S)-1a, affording the optically active γ- and δ-hydroxy acids/lactones in high yields with excellent enantioselectivities (up to >99% ee) and turnover numbers (TON up to 100000). This protocol provides an efficient and practical method for enantioselective synthesis of Ezetimibe.

2.
Phytopathology ; 110(1): 187-193, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31516080

RESUMO

Potyviral helper component protease (HC-Pro), as a major determinant of symptom expression in susceptible plants, is a likely target candidate in the production of attenuated strains for cross-protection. In this study, single or double mutations of Lys (K) to Glu (E) in the Lys-Ile-Thr-Cys motif and Arg (R) to Ile (I) in the Phe-Arg-Asn-Lys motif of the HC-Pro from the severe papaya leaf distortion mosaic virus strain DF (PLDMV-DF) reduced symptom expression and virus accumulation in infected papaya (Carica papaya) plants. The papaya plants infected with the attenuated double mutant of PLDMV-EI presented as symptomless. PLDMV-EI provided effective protection against PLDMV-DF infection in three papaya cultivars and had no effect on plant growth and development. Our result showed that PLDMV-EI is a promising mild strain for the practical use of cross-protection in the field.


Assuntos
Motivos de Aminoácidos , Carica , Peptídeo Hidrolases , Potyvirus , Motivos de Aminoácidos/genética , Carica/virologia , Mutação/genética , Peptídeo Hidrolases/genética , Potyvirus/enzimologia , Potyvirus/genética
3.
Int J Cancer ; 146(1): 103-114, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31199508

RESUMO

Next-generation sequencing of cell-free circulating DNA (cfDNA) has emerged as promising technique for identifying minimally invasive genomic profiling of tumor cells recently. However, it remains relatively unknown in LAM disease. In our study, paired cfDNA and genomic DNA (gDNA) in blood samples were obtained from 23 LAM patients and seven healthy controls to explore mutations profiles of targeted 70 cancer-related genes. As results, log2-based allele frequencies of mutations in cfDNA were significantly different from those of gDNA. By comparing the mutual mutations identified both in cfDNA and gDNA, a significant correlation was also observed. After removing mutations in gDNA, distinct somatic mutation profiles of cfDNA were observed in LAM patients. Forty of 70 targeted genes had recurrent mutations, of which ATM, BRCA2 and APC showed the highest frequency. Based on the mutation, correlation network constructed of 40 mutated genes, 11 hub genes bearing intensive interactions were highlighted, including BRCA1, BRCA2, RAD50, RB1, NF1, APC, MLH3, ATM, PDGFRA, PALB2 and BLM. Expression of the hub genes showed significant clusters between LAM patients and controls and that RAD50 and BRCA2 had the strongest associations with subject phenotypes. Myogenesis and estrogen response were confirmed to be positively regulated in LAM patients. Collectively, our study provided a landscape of genomic alterations in LAM and discovered several potential driver genes, that is, BRCA2 and RAD50, which shed a substantial light on the clinical application of key molecular markers and potential therapy targets for precision diagnosis and treatment in the future.


Assuntos
Ácidos Nucleicos Livres/genética , Neoplasias Pulmonares/genética , Linfangioleiomiomatose/genética , Mutação/genética , Adulto , Proteína BRCA2/genética , DNA Tumoral Circulante/genética , DNA de Neoplasias/genética , Proteínas de Ligação a DNA/genética , Feminino , Frequência do Gene/genética , Genoma/genética , Genômica/métodos , Humanos , Masculino , Pessoa de Meia-Idade
4.
J Virol Methods ; : 113795, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31809783

RESUMO

Two reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assays were developed for the detection of areca palm necrotic ringspot virus (ANRSV) and areca palm necrotic spindle-spot virus (ANSSV), respectively. These two emerging viruses both induce necrotic symptoms in areca palms. The coat protein (CP) gene of ANRSV and the 9 K gene of ANSSV were used to design the respective RT-LAMP primers for the assays. Each set of four primers designed for each of these viruses was found to be highly specific in the detection of the respective targeted virus. The optimal incubation conditions for the RT-LAMP assays were 63 °C for 40 min for ANRSV and at 61 °C for 40 min for ANSSV. The sensitivity of the RT-LAMP method for each of these viruses was 10-fold greater than that of the corresponding conventional reverse-transcription polymerase chain reaction (RT-PCR). The RT-LAMP assays may be useful for the rapid early detection of ANSSV and ANRSV in commercial areca palm production.

5.
Radiol Case Rep ; 14(11): 1352-1355, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31516651

RESUMO

Background: Dermoid cysts are benign tumors rarely arising from the cecum. Also, including this report, 10 cases have been described in the literature, to our knowledge. Dermoid cysts are benign tumors rarely found in the cecum. A literature research has found only 9 other cases. Case: We describe the case of a healthy 44-year-old man with no surgical history, in whom a well-defined cystic-mass was incidentally found on abdominal computed tomography, presenting as an appendicular mucocele. An hemicolectomy was performed and pathological analysis revealed a dermoid cyst of the cecum. This paper describes the case of a healthy 44-year-old male with no prior surgical history, with a well-defined cystic mass found incidentally on abdominal computed tomography, thought to be an appendicular mucocele. After hemicolectomy and pathological analysis, this was revealed to be a dermoid cyst of the cecum. Conclusion: Although dermoid cysts are a rare tumor of the cecum, they should be considered in the differential diagnosis of a nontender palpate mass in right lower quadrant (RLQ) or cecal mass on imaging. Although rarely found in the cecum, a dermoid cyst should be included in the differential diagnosis of nontender palpable masses of the RLQ, or if revealed by imagery.

6.
Comput Intell Neurosci ; 2019: 1019749, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31485215

RESUMO

Product color plays a vital role in shaping brand style and affecting users' purchase decision. However, users' preferences about product color design schemes may vary due to their cognition differences. Although considering users' perception of product color has been widely performed by industrial designers, it is not effective to support this activity. In order to provide users with plentiful product color solutions as well as embody users' preference into product design process, involving users in interactive genetic algorithms (IGAs) is an effectual way to find optimum solutions. Nevertheless, cognition difference and uncertainty among users may lead to various understanding in line with IGA progressing. To address this issue, this study presents an advanced IGA by combining users' cognition noise which includes cognition phase, intermediate phase, and fatigue phase. Trapezoidal fuzzy numbers are employed to represent uncertainty of users' evaluations. An algorithm is designed to find key parameters through similarity calculation between RGB value and their area proportion of two individuals and users' judgment. The interactive product color design process is put forward with an instance by comparing with an ordinary IGA. Results show that (1) knowledge background will significantly affect users' cognition about product colors and (2) the proposed method is helpful to improve convergence speed and evolution efficiency with convergence increasing from 67.5% to 82.5% and overall average evolutionary generations decreasing from 18.15 to 15.825. It is promising that the proposed method can help reduce users' cognition noise, promote convergence, and improve evolution efficiency of interactive product color design.

7.
Am J Transl Res ; 11(5): 2908-2924, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31217863

RESUMO

Current clinical approaches to treat irradiation-induced salivary gland hypofunction are ineffective. We previously reported that adipose-derived stem cell (ADSC)-based therapy ameliorates damaged salivary gland function in mice and that the effects were enhanced when the therapy was co-administrated with platelet-rich fibrin (PRF). We examined the feasibility of ADSC transdifferentiation into salivary gland acinar-like cells (SGALCs) and analyzed the potential of PRF to promote the transdifferentiation process in vitro. Salivary gland cells (SGCs) and ADSCs were indirectly co-cultured using Transwell inserts, and increasing concentrations of PRF-conditioned medium were applied to the co-culture system. The expression of α-amylase and AQP-5 were used to evaluate ADSC transdifferentiation. Notably, on day 7, 14, and 21, expression of both α-amylase and AQP-5 were detected in the co-cultured ADSCs. Additionally, PRF increased α-amylase and AQP-5 levels in ADSCs that were co-cultured for 7 days. These data demonstrate that ADSCs have the potential to transdifferentiate into SGALCs and that PRF can promote the transdifferentiation process. Therefore, these data reveal a possible mechanism to treat irradiation-induced salivary gland hypofunction and have translational medicine implications.

8.
J Cell Physiol ; 234(12): 21915-21924, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31041827

RESUMO

Diabetic retinopathy (DR) remains the leading cause of blindness in adults with diabetes mellitus. Numerous microRNAs (miRNAs) have been identified to modulate the pathogenesis of DR. The main purpose of this study was to evaluate the potential roles of miR-455-5p in high glucose (HG)-treated retinal pigment epithelial (RPE) cells and underlying mechanisms. Our present investigation discovered that the expression of miR-455-5p was apparently downregulated in ARPE-19 cells stimulated with HG. In addition, forced expression of miR-455-5p markedly enhanced cell viability and restrained HG-induced apoptosis accompanied by decreased BCL2-associated X protein (Bax)/B-cell leukemia/lymphoma 2 (Bcl-2) ratio and expression of apoptotic marker cleaved caspase-3 during HG challenged. Subsequently, augmentation of miR-455-5p remarkably alleviated HG-triggered oxidative stress injury as reflected by decreased the production of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) content as well as NADPH oxidase 4 expression, concomitant with enhanced the activities of superoxide dismutase, catalase, and GPX stimulated with HG. Furthermore, enforced expression of miR-455-5p effectively ameliorated HG-stimulated inflammatory response as exemplified by repressing the secretion of inflammatory cytokines interleukin 1ß (IL-1ß), IL-6, and tumour necrosis factor-α in ARPE-19 cells challenged by HG. Most importantly, we successfully identified suppressor of cytokine signaling 3 (SOCS3) as a direct target gene of miR-455-5p, and miR-455-5p negatively regulated the expression of SOCS3. Mechanistically, restoration of SOCS3 abrogated the beneficial effects of miR-455-5p on apoptosis, accumulation of ROS, and inflammatory factors production in response to HG. Taken together, these findings demonstrated that miR-455-5p relieved HG-induced damage through repressing apoptosis, oxidant stress, and inflammatory response by targeting SOCS3. The study gives evidence that miR-455-5p may serve as a new potential therapeutic agent for DR treatment.

9.
Neurosci Res ; 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31891740

RESUMO

Resveratrol shows ability to eliminate prion replication, but the exact mechanism for prion eradication was not clear yet. Our previous studies demonstrate a downregulation of brain-derived nerve growth factor (BDNF) during prion infection, meanwhile recovery of cerebral nerve growth factor (NGF) level by resveratrol treatment has been reported in other neurodegenerative models. To obtain the possible changes of brain NGF and its upstream regulatory cascade during prion infection and after removal of prion propagation, the levels of NGF and its upstream regulatory factors in various prion-infected and prion-eradicated SMB cell lines and mice brains inoculated with various SMB cellular lysates were assessed with various methodologies. The levels of NGF were significantly decreased during prion replication, while recovered after removal of PrPSc by resveratrol in vitro. Morphological assays revealed that the NGF signals mainly colocalized within neurons, but not in the proliferative astrocytes and microglia. The upstream positive regulatory kinases, such as p-CREB, p-CaMKIV, CaMKK2 were decreased in the prion infected cells and mice brains, whereas the negative regulatory one, p-CaMKK2, was increased. The aberrant situations of those kinases in prion infected cell lines or mice brains could be also partially reversed by removal of prion agent. Moreover, we demonstrated that the signals of CaMKK2 and p-CaMKK2 were also distributed predominately in neurons in the brain tissues. The data illustrate a direct linkage of abnormally repressive NGF and its upstream regulatory kinases with prion infection. Resveratrol has not only the ability to inhibit prion replication, but also to improve the expression of NGF via CaMKK2/CaMKIV cascade, which might benefit the microenvironment in brains.

10.
Virus Genes ; 54(6): 833-839, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30218292

RESUMO

We used green fluorescent protein (GFP)-tagged Papaya leaf distortion mosaic virus (PLDMV-GFP) to track PLDMV infection by fluorescence. The virus-derived small interfering RNAs (vsiRNAs) of PLDMV-GFP were characterized from papaya plants by next-generation sequencing. The foreign GFP gene inserted into the PLDMV genome was also processed as a viral gene into siRNAs by components involved in RNA silencing. The siRNAs derived from PLDMV-GFP accumulated preferentially as 21- and 22-nucleotide (nt) lengths, and most of the 5'-terminal ends were biased towards uridine (U) and adenosine (A). The single-nucleotide resolution map revealed that vsiRNAs were heterogeneously distributed throughout the PLDMV-GFP genome, and vsiRNAs derived from the sense strand were more abundant than those from the antisense strand. The hotspots were mainly distributed in the P1 and GFP coding region of the antisense strand. In addition, 979 papaya genes targeted by the most abundant 1000 PLDMV-GFP vsiRNAs were predicted and annotated using GO and KEGG classification. Results suggest that vsiRNAs play key roles in PLDMV-papaya interactions. These data on the characterization of PLDMV-GFP vsiRNAs will help to provide insight into the function of vsiRNAs and their host target regulation patterns.


Assuntos
Carica/virologia , Potyvirus/isolamento & purificação , RNA Interferente Pequeno/genética , RNA Viral/genética , Carica/genética , Carica/crescimento & desenvolvimento , Genoma Viral/genética , Proteínas de Fluorescência Verde/genética , Sequenciamento de Nucleotídeos em Larga Escala , Doenças das Plantas/genética , Doenças das Plantas/virologia , Potyvirus/genética , Potyvirus/patogenicidade , Interferência de RNA
11.
Oncoimmunology ; 7(8): e1462878, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30221058

RESUMO

Increased density of tumor-associated lymphatic vessels correlates with poor patient survival in melanoma and other cancers, yet lymphatic drainage is essential for initiating an immune response. Here we asked whether and how lymphatic vessel density (LVD) correlates with immune cell infiltration in primary tumors and lymph nodes (LNs) from patients with cutaneous melanoma. Using immunohistochemistry and quantitative image analysis, we found significant positive correlations between LVD and CD8+ T cell infiltration as well as expression of the immunosuppressive molecules inducible nitric oxide synthase (iNOS) and 2,3-dioxygénase (IDO). Interestingly, similar associations were seen in tumor-free LNs adjacent to metastatic ones, indicating loco-regional effects of tumors. Our data suggest that lymphatic vessels play multiple roles at tumor sites and LNs, promoting both T cell infiltration and adaptive immunosuppressive mechanisms. Lymph vessel associated T cell infiltration may increase immunotherapy success rates provided that the treatment overcomes adaptive immune resistance.

12.
Cancer Biomark ; 23(1): 145-156, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30010111

RESUMO

OBJECTIVE: Colorectal cancer (CRC) is the 3rd most common cancer worldwide. Recently, long non-coding RNAs (lncRNAs) were found to be critical modulators in the CRC progression. The aim of this study is to investigate the potential roles of lncRNA P73 antisense RNA 1T (TP73-AS1) in CRC development and progression. METHODS: Quantitative real-time PCR (qRT-PCR) was performed to determine relevant gene expression levels; western blot was performed to determine protein expression levels; CCK-8, colony formation, wound healing and Transwell invasion assays were used to determined CRC cell proliferation, migration and invasion; in vivo tumor growth was assessed in xenograft mice model. RESULTS: TP73-AS1 was up-regulated in both CRC tissues and CRC cell lines. Overexpression of TP73-AS1 was associated with metastasis and advanced clinical stages in CRC patients. Overexpression of TP73-AS1 promoted CRC cell growth, proliferation, migration and invasion in vitro; and knockdown of TP73-AS1 significantly inhibited CRC cell growth, proliferation, migration and invasion in vitro as well as tumor growth in vivo. Bioinformatics analysis and luciferase reporter assay indicated that TP73-AS1 could bind directly with miR-194, and TP73-AS1 negatively regulated the expression of miR-194 in CRC cells. Further study indicated that miR-194 negatively regulated the downstream target of transforming growth factor alpha (TGFα) via targeting its 3' untranslated region, and TP73-AS1 positively regulated the expression of TGFα in CRC cells. Moreover, overexpression of miR-194 suppressed CRC cell proliferation and invasion, and attenuated the effects of TP73-AS1 overexpression on CRC cell proliferation and invasion. Silence of TGFα inhibited CRC cell proliferation and invasion, and also reversed the effects of TP73-AS1 overexpression on CRC cell proliferation and invasion. CONCLUSIONS: this study demonstrated that TP73-AS1 regulated CRC progression by acting as a competitive endogenous RNA to sponge miR-194 to modulate the expression of TGFα.


Assuntos
Neoplasias Colorretais/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Fator de Crescimento Transformador alfa/genética , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , RNA Antissenso/genética , RNA Antissenso/farmacologia , RNA Longo não Codificante/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto
13.
PLoS One ; 13(6): e0199762, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29953550

RESUMO

The calorific value (CAL, KJ g-1) of different plant organs are important plant traits. Variation in CAL among different plant organs reflects the energy utilization and distribution strategy of plant. Here, we explored how the CAL of different plant organs varies at the species and regional level in relation to vegetation type (3697 forests samples, 430 grasslands samples, and 146 deserts samples). The results showed that, in the forests and grasslands, CAL significantly differed among the different organs and functional types of plants. The CAL of different organs in forests was ordered as: leaf (19.71 ± 1.82 KJ g-1) > branch (19.33 ± 1.32 KJ g-1) > trunk (19.09 ± 1.44 KJ g-1) > root (19.02 ± 1.11 KJ g-1). For forests, the CAL of plant organs, except for the leaves of trees and shrubs, increased with increasing latitude (P < 0.01). In comparison, the CAL in the roots of shrubs and herbs decreased with increasing longitude (P < 0.01). Through delineating systematic references of CAL among different plant organs, our findings provide key parameters to improve estimates of biomass energy at regional and global scales.


Assuntos
Componentes Aéreos da Planta/química , Plantas/química , China
14.
Eur J Cancer ; 99: 66-77, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29909091

RESUMO

PURPOSE: Irinotecan (CPT-11) in combination with 5-fluorouracil (5FU) is widely used in the treatment of colorectal cancer. We assessed potential clinical variables that may predict toxicity and more specifically the role of UGT1A1 polymorphisms associated with irinotecan toxicity. We used data from the PETACC3 trial, which randomised patients in adjuvant setting to 6 months of leucovorin (LV) and 5FU (LV5/FU2) or LV5/FU2 + irinotecan. PATIENTS AND METHODS: Clinical and toxicity data were available for 2982 patients, DNA was available for 1200 (40%) of these patients. We genotyped the polymorphisms UGT1A1*28 and UGT1A1-3156G > A. Risk factors for neutropenia and diarrhoea were assessed by univariable and multivariable analyses. RESULTS: In univariable analysis, UGT1A*28 genotype was associated with an increased incidence of grade III-IV neutropenia (incidence: 44% versus 26%; odds ratio [OR]: 2.3; 95% confidence interval [CI]: 1.4-3.7). In multivariable analysis, the most important predictors (ordered in terms of contribution to R2) were baseline neutrophil count (OR for 1-unit (109/l) decrease: 1.8, 95% CI: 1.3-1.7), female sex (OR: 1.8, 95% CI: 1.1-3.0), body surface area (OR for 0.1-unit increase: 0.8, 95% CI: 0.7-1.0), UGT1A1 (OR: 2.8, 95% CI: 1.6-5.0), age (OR per 10 years: 1.3, 95% CI: 1.1-1.6) and poor performance status (OR: 1.6, 95% CI: 1.0-2.6). The main predictors for grade IV neutropenia were sex, age, performance score and UGT1A1. The main predictors for diarrhoea were sex and age. CONCLUSIONS: We found that a complex of risk factors is involved in the development of toxicity, including UGT1A1. Parameters that are readily available in clinical practice, notably sex, age and performance status, are stronger predictors than the UGT1A1*28 genotype. Further studies beyond the UGT1A1*28 genotype are needed to fully understand the determinants of toxicity risk, notably in females.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Diarreia/epidemiologia , Glucuronosiltransferase/genética , Neutropenia/epidemiologia , Adulto , Fatores Etários , Idoso , Biomarcadores Farmacológicos/sangue , Superfície Corporal , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Diarreia/induzido quimicamente , Feminino , Fluoruracila/efeitos adversos , Humanos , Incidência , Irinotecano/efeitos adversos , Leucovorina/efeitos adversos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neutropenia/sangue , Neutropenia/induzido quimicamente , Neutropenia/genética , Neutrófilos , Fatores Sexuais , Resultado do Tratamento , Adulto Jovem
15.
Protein Expr Purif ; 146: 17-22, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29373846

RESUMO

Plant methionine sulfoxide reductase B1 (MsrB1) protects the photosynthetic apparatus from oxidative damage by scavenging reactive oxygen species to repair Met-oxidized proteins in response to abiotic stresses and biotic attack. Papaya MsrB1 (PaMsrB1) was identified previously to interact with papaya ringspot virus NIa-Pro, and this interaction inhibits the import of PaMsrB1 into the chloroplast. Further functional characterization of PaMsrB1 requires the production of a biologically active purified recombinant protein. In this report, PaMsrB1 as a fusion protein containing an N-terminal maltose-binding protein (MBP) was expressed in Escherichia coli Rosetta (DE3) cells and purified. Production of soluble fusion protein was greater when the cells were cultured at 16 °C than at 37 °C. The Factor Xa protease digested MBP-PaMsrB1 fusion protein and subsequently purified recombinant PaMsrB1 specifically reduced the R-diastereomer of methionine sulfoxide (MetSO) and Dabsyl-MetSO to Met in the presence of dithiothreitol. Eight chloroplast-localized and five non-chloroplast-localized candidate proteins that interact with PaMsrB1 were isolated by affinity chromatography and liquid chromatography coupled to tandem mass spectrometry. The results provide a platform to further understand the anti-oxidative defense mechanism of PaMsrB1.


Assuntos
Carica/enzimologia , Metionina Sulfóxido Redutases/metabolismo , Mapas de Interação de Proteínas , Sequência de Aminoácidos , Carica/química , Carica/genética , Carica/metabolismo , Cloroplastos/genética , Cloroplastos/metabolismo , Escherichia coli/genética , Expressão Gênica , Metionina Sulfóxido Redutases/química , Metionina Sulfóxido Redutases/genética , Oxirredução , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Solubilidade
16.
Eur J Cancer ; 89: 82-89, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29241084

RESUMO

BACKGROUND: KRAS mutation occurs in ∼40% of locally advanced rectal cancers (LARCs). The multitarget tyrosine kinase inhibitor sorafenib has radiosensitising effects and might improve outcomes for standard preoperative chemoradiotherapy in patients with KRAS-mutated LARC. METHODS: Adult patients with KRAS-mutated T3/4 and/or N1/2M0 LARC were included in this phase I/II study. The phase I dose-escalation study of capecitabine plus sorafenib and radiotherapy was followed by a phase II study assessing efficacy and safety. Primary end-points were to: establish the maximum tolerated dose of the regimen in phase I; determine the pathologic complete response (pCR) rate in phase II defined as Dworak regression grade 3 and 4. RESULTS: Fifty-four patients were treated at 18 centres in Switzerland and Hungary; 40 patients were included in the single-arm phase II study. Recommended doses from phase I comprised radiotherapy (45 Gy in 25 fractions over 5 weeks) with capecitabine 825 mg/m2 twice daily × 33 plus sorafenib 400 mg/d. Median daily dose intensity in phase II was radiotherapy 100%, capecitabine 98.6%, and sorafenib 100%. The pCR rate (Dworak 3/4) was 60% (95% CI, 43.3-75.1%) by central independent pathologic review. Sphincter preservation was achieved in 89.5%, R0 resection in 94.7%, and downstaging in 81.6%. The most common grade 3 toxicities during phase II included diarrhoea (15.0%), skin toxicity outside radiotherapy field (12.5%), pain (7.5%), skin toxicity in radiotherapy field, proctitis, fatigue and cardiac ischaemia (each 5%). CONCLUSIONS: Combining sorafenib and standard chemoradiotherapy with capecitabine is highly active in patients with KRAS-mutated LARC with acceptable toxicity and deserves further investigation. www.clinicaltrials.gov: NCT00869570.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Retais/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Quimiorradioterapia/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Niacinamida/administração & dosagem , Niacinamida/efeitos adversos , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Radioterapia Adjuvante/efeitos adversos , Neoplasias Retais/genética , Sorafenibe
17.
Virology ; 510: 99-103, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28715654

RESUMO

A novel Rhizobium radiobacter (synonym Agrobacterium tumefaciens)-mediated approach was developed to generate stable infectious clones of plant viruses. This method uses R. radiobacter for both cloning and inoculation of infectious clones, bypassing the requirement of cloning in E. coli to avoid the instability. Only three steps are included in this method: (i) construct viral genome-encoding plasmids in vitro by one-step Gibson assembly; (ii) transform the assembled DNA products into R. radiobacter; (iii) inoculate plants with the R. radiobacter clones containing the viral genome. Stable infectious clones were obtained from two potyviruses papaya ringspot virus (PRSV) and papaya leaf distortion mosaic virus (PLDMV) using this method, whereas attempts utilizing "classical" E. coli cloning system failed repeatedly. This method is simple and efficient, and is promising for a wide application in generation of infectious clones of plant virus, especially for those which are instable in E. coli.


Assuntos
Agrobacterium tumefaciens/genética , Clonagem Molecular , Potyvirus/genética , Genética Reversa , Virologia/métodos , Plantas/virologia , Transformação Genética
18.
Chin Med J (Engl) ; 130(11): 1296-1302, 2017 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-28524828

RESUMO

BACKGROUND: Atherosclerosis (AS) is an inflammatory disease. Inflammation was considered to play a role in the whole process of AS. This study aimed to analyze the relationships of inflammatory factors and risk factors with different target organ damages (TOD) in essential hypertension (EH) patients and to explore its clinical significance. METHODS: A total of 294 EH patients were selected and divided into four groups according to their conditions of TOD. Forty-eight healthy subjects were selected as control. The clinical biochemical parameters, serum amyloid A, serum tryptase, and lipoprotein-associated phospholipase A2 (Lp-PLA2) in each group were detected, and the related risk factors were also statistically analyzed. RESULTS: Fibrinogen (Fbg) was the most significant independent risk factor in acute coronary syndrome (ACS) group (odds ratio [OR]: 22.242, 95% confidence interval [CI]: 6.458-76.609, P< 0.001) with the largest absolute value of the standardized partial regression coefficient B' (b': 1.079). Lp-PLA2 was the most significant independent risk factor in stroke group (OR: 13.699, 95% CI: 5.236-35.837, P< 0.001) with b' = 0.708. Uric acid (UA) was the most significant independent risk factor in renal damage group (OR: 15.307, 95% CI: 4.022-58.250, P< 0.001) with b' = 1.026. CONCLUSIONS: Fbg, Lp-PLA2, and UA are the strongest independent risk factors toward the occurrence of ACS, ischemic stroke, and renal damage in EH patients, thus exhibiting the greatest impacts on the occurrence of ACS, ischemic stroke, and renal damage in EH patients, respectively.


Assuntos
Hipertensão Essencial/sangue , Hipertensão Essencial/fisiopatologia , 1-Alquil-2-acetilglicerofosfocolina Esterase , Idoso , Anti-Hipertensivos/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Hipertensão Essencial/complicações , Hipertensão Essencial/tratamento farmacológico , Feminino , Humanos , Nefropatias/sangue , Nefropatias/etiologia , Nefropatias/fisiopatologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Proteína Amiloide A Sérica/metabolismo , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia , Triptases/sangue
19.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 33(4): 460-464, 2017 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-28395714

RESUMO

Objective To determine the expiration dates of CD3e+CD4+ T and CD3e+CD8a+ T lymphocytes of Kunming mice. Methods The sterile spleen and anticoagulant blood of Kunming mice were collected and used to prepare the single-cell suspensions. After CD3e, CD4 and CD8a of T cells were stained with fluorophore-conjugated monoclonal antibodies, the samples were fixed with paraformaldehyde (PFA) and stored at 4DegreesCelsius in dark followed by detection using three-color flow cytometry at several specific time points. The best regression curves fitted with the least squares method were used for calculating the contents of T cells at each time point and the subsequent statistical analysis. Samples without PFA served as the blank controls. Results The levels of PFA-fixed CD3e+CD4+ T and CD3e+CD8a+ T lymphocytes from spleen tissues significantly decreased at 11 days and 16 days post collection, respectively; whereas no difference was found in the samples without PFA until 8 days and 11 days post collection, respectively. As for the T cells separated from the peripheral blood, the longer storage periods were both 18 days under the PFA fixation, which were longer than those of the blank controls (10 and 15 days, respectively). Conclusion The PFA-fixed T lymphocytes of the spleen and peripheral blood of Kunming mice should be detected using flow cytometry within 11 days post collection.


Assuntos
Técnicas Citológicas/métodos , Linfócitos T/química , Linfócitos T/citologia , Animais , Feminino , Citometria de Fluxo , Formaldeído/química , Contagem de Linfócitos , Masculino , Camundongos , Polímeros/química , Fatores de Tempo
20.
Comput Intell Neurosci ; 2017: 9740278, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28316619

RESUMO

Consumers' opinions toward product design alternatives are often subjective and perceptual, which reflect their perception about a product and can be described using Kansei adjectives. Therefore, Kansei evaluation is often employed to determine consumers' preference. However, how to identify and improve the reliability of consumers' Kansei evaluation opinions toward design alternatives has an important role in adding additional insurance and reducing uncertainty to successful product design. To solve this problem, this study employs a consensus model to measure consistence among consumers' opinions, and an advanced particle swarm optimization (PSO) algorithm combined with Linearly Decreasing Inertia Weight (LDW) method is proposed for consensus reaching by minimizing adjustment of consumers' opinions. Furthermore, the process of the proposed method is presented and the details are illustrated using an example of electronic scooter design evaluation. The case study reveals that the proposed method is promising for reaching a consensus through searching optimal solutions by PSO and improving the reliability of consumers' evaluation opinions toward design alternatives according to Kansei indexes.


Assuntos
Algoritmos , Simulação por Computador , Consenso , Comportamento do Consumidor , Humanos , Modelos Teóricos
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