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4.
Clin Nutr ; 42(10): 1932-1939, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37634307

RESUMO

BACKGROUND: Postoperative skeletal muscle loss (SM loss) was reported to be associated with a poor prognosis in early-stage non-small cell lung cancer (NSCLC). Small airway dysfunction (SAD) is a common but neglected respiratory abnormality. Little information is known about the association between preoperative SAD and postoperative SM loss in early-stage NSCLC. Therefore, this study aimed to investigate the correlation between preoperative SAD and SM loss after surgery in early-stage NSCLC patients. METHODS: There were 348 NSCLC patients with stages I-IIIA in this study from January 2017 to December 2020. All CT images were contrast-enhanced scans, and the skeletal muscle index (SMI) was measured using CT images. A 10.0% decrease in SMI over 12 months was determined as the cut-off value to define excessive SM loss. Logistic regression analyses were used to examine the relationship between SAD and SM loss. RESULTS: This study included 348 subjects who underwent pulmonary operation (159 males and 189 females; mean age: 57.5 ± 8.8 years). 152 (43.7%) patients were identified as having SAD before surgery, and 179 patients (51.4%) were identified as having SM loss after 1 year. Moreover, a higher incidence of SAD was found in the SM loss group compared with that in the non-SM loss group (52.0% vs. 34.9%, p = 0.001). The patients with SAD were older, had larger tumor size, and had lower albumin levels. Furthermore, there were significant correlations between the lung function parameters manifesting SAD and the percentage change in SMI (for the forced expiratory flow when 75% of forced vital capacity has been exhaled (FEF75%), Pearson r=-0.107, p = 0.046; for FEF50%, r = -0.142, p = 0.008; and for FEF25-75%, r=-0.124, p = 0.021; respectively). However, no significant correlations were found between SMI and the lung function parameters reflecting proximal airway obstruction (p > 0.05). Logistic regression analysis revealed that preoperative SAD (HR, 2.465; 95% CI, 1.256-4.838; p = 0.009) was independent risk factor for postoperative SM loss in early-stage NSCLC. In addition, multivariable analysis revealed that SAD (HR, 1.816; 95% CI, 1.025-3.216, P = 0.041) were associated with postoperative complications. CONCLUSION: Preoperative SAD is significantly associated with postoperative complications and SM loss in early NSCLC patients. Our results suggest that preoperative assessment of SAD may be useful for risk stratification of surgical candidates with potential for targeted interventions.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Prognóstico , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos
5.
Chin J Integr Med ; 29(11): 971-979, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37118531

RESUMO

OBJECTIVE: To analyze the factors related to pregnancy of endometriosis and whether Chinese herbal medicines (CHMs) can improve pregnancy outcomes in patients with endometriosis in long-term management. METHODS: This multicenter cohort study retrospectively analyzed the clinical data of endometriosis patients with fertility needs from January 2019 to November 2019. A total of 252 patients with endometriosis from 5 level-III Grade A hospitals in Beijing were included in this study. Univariate and multivariate logistic regression analysis were performed for the relevant factors. The propensity score matching (PSM) function of SPSS software was used to match the CHMs group with the non-CHMs group. The pregnancy rate and live birth rate were analyzed. RESULTS: The results of univariate analysis showed that age, disease course, presence of infertility, presence of adenomyosis, time after surgery or use of gonadotropin-releasing hormone agonist (GnRH-a), use of CHMs and follow-up time were influencing factors of pregnancy in endometriosis patients (P<0.05). The results of multivariate analysis showed that age, presence of adenomyosis, time after surgery or use of GnRH-a, use of CHMs and follow-up time were independent factors affecting pregnancy in endometriosis patients, among which, age ⩾35 years old, presence of adenomyosis and follow-up time >6 months were independent risk factors (OR=0.445, 0.348, 0.140, respectively, P<0.05), time after surgery or use of GnRH-a ⩽6 months and use of CHMs were independent protective factors (OR=3.839, 3.842, respectively, P<0.05). After PSM, 99 pairs of two groups were matched successfully. The pregnancy rate of the CHMs group was higher than that of the non-CHMs group [55.56% (55/99) vs. 36.36% (36/99), P<0.05]. The live birth rate of the CHMs group was higher than that of the non-CHMs group [49.49% (49/99) vs. 35.35% (35/99), P<0.05]. CONCLUSION: CHMs can effectively improve clinical pregnancy rate and live birth rate of patients with endometriosis in the chronic disease management.


Assuntos
Adenomiose , Endometriose , Gravidez , Feminino , Humanos , Adulto , Resultado da Gravidez , Endometriose/complicações , Endometriose/tratamento farmacológico , Endometriose/cirurgia , Estudos Retrospectivos , Estudos de Coortes , Hormônio Liberador de Gonadotropina , Extratos Vegetais , Fertilização in vitro
6.
Respir Res ; 23(1): 328, 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36463140

RESUMO

BACKGROUND: Bronchiectasis is a highly heterogeneous chronic airway disease with marked geographic and ethnic variations. Most influential cohort studies to date have been performed in Europe and USA, which serve as the examples for developing a cohort study in China where there is a high burden of bronchiectasis. The Establishment of China Bronchiectasis Registry and Research Collaboration (BE-China) is designed to: (1) describe the clinical characteristics and natural history of bronchiectasis in China and identify the differences of bronchiectasis between the western countries and China; (2) identify the risk factors associated with disease progression in Chinese population; (3) elucidate the phenotype and endotype of bronchiectasis by integrating the genome, microbiome, proteome, and transcriptome with detailed clinical data; (4) facilitate large randomized controlled trials in China. METHODS: The BE-China is an ongoing prospective, longitudinal, multi-center, observational cohort study aiming to recruit a minimum of 10,000 patients, which was initiated in January 2020 in China. Comprehensive data, including medical history, aetiological testing, lung function, microbiological profiles, radiological scores, comorbidities, mental status, and quality of life (QoL), will be collected at baseline. Patients will be followed up annually for up to 10 years to record longitudinal data on outcomes, treatment patterns and QoL. Biospecimens, if possible, will be collected and stored at - 80 °C for further research. Up to October 2021, the BE-China has enrolled 3758 patients, and collected 666 blood samples and 196 sputum samples from 91 medical centers. The study protocol has been approved by the Shanghai Pulmonary Hospital ethics committee, and all collaborating centers have received approvals from their local ethics committee. All patients will be required to provide written informed consent to their participation. CONCLUSIONS: Findings of the BE-China will be crucial to reveal the clinical characteristics and natural history of bronchiectasis and facilitate evidence-based clinical practice in China. Trial registration Registration Number in ClinicalTrials.gov: NCT03643653.


Assuntos
Bronquiectasia , Humanos , Bronquiectasia/diagnóstico , Bronquiectasia/epidemiologia , China/epidemiologia , Estudos de Coortes , Estudos Multicêntricos como Assunto , Estudos Observacionais como Assunto , Estudos Prospectivos , Qualidade de Vida , Sistema de Registros
7.
Am J Transl Res ; 13(5): 4464-4476, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34150027

RESUMO

With the advancement of tumor subtype-specific treatments, precise histopathologic distinction between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) is of significant clinical importance. Nevertheless, the current markers are insufficiently precise in poorly differentiated tissue. This study aimed to establish a histology-specific immunomarker combination to subclassify non-small cell lung cancer (NSCLC) specimens. Based on previous work, we assessed the differential expression of anterior gradient 2 (AGR2) and keratin 5 (KRT5) in ADC and SCC by analyzing public datasets and postoperative specimens. Subsequently, we established a train set (n = 188) and a validation set (n = 42) comprised of NSCLC surgical specimens for training and verifying the subtype-identification capabilities of the two biomarkers separately and in combination, and contrasted the diagnostic utility of AGR2-KRT5 with that of the classic immunomarker combination, TTF1-P40. Differential expression of the two genes was statistically significant in ADC and SCC samples, both at the mRNA and protein levels. The specificity and sensitivity of AGR2 to detect ADC in the training set were 97.0% and 94.4%, while the sensitivity and specificity of KRT5 to determine SCC were 93.9% and 98.9%, respectively. The accuracies of AGR2-KRT5 in ADC, SCC, and across all samples were 93.3%, 92.0% and 92.6% respectively. In the validation cohort, the predictive accuracy of AGR2-KRT5 was up to 100% for ADC and 86.7% for SCC. Compared with TTF1-P40 in ADC samples, AGR2-KRT5 had 8.4% higher accuracy. In summary, the AGR2-KRT5 immunomarker combination reliably distinguished SCC from ADC, and was more accurate than TTF1-P40 in ADC.

8.
Chin J Integr Med ; 26(2): 92-99, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31997236

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of Chinese medicine (CM) improving pregnancy outcomes after surgery for endometriosis-associated infertility. METHODS: A multicenter, randomized, double-blind placebo parallel controlled clinical trial was designed. A total of 202 patients who had laparoscopy for endometriosis-associated infertility with qi stagnation and blood stasis syndrome were included and randomly divided into the CM treatment group and placebo control group at a ratio of 1:1 using a central block randomization from May 2014 to September 2017, 101 patients in each group. The two groups received continuous intervention at 1-5 days after surgery, for 6 menstrual cycles. Before ovulation, the CM group was treated Huoxue Xiaoyi Granule (); after ovulation, Bushen Zhuyun Granule ( was involved. The control group was treated with placebo. Transvaginal ultrasonography was performed every menstrual cycle during the treatment, and female hormone levels in the follicular and luteal phases were measured during the 1st, 3rd and 6th menstrual cycles. The analysis was continued until pregnancy. The primary outcomes were clinical pregnancy rate and pregnancy outcome, and the secondary outcomes were follicular development and endometrial receptivity. Safety evaluations were performed before and after treatment. RESULTS: (1) Clinical pregnancy and live birth rates: the clinical pregnancy and live birth rates of the CM group were significantly higher than those of the placebo group [44.6% (45/101) vs. 29.7% (30/101), 34.7% (35/101) vs. 20.8% (21/101), both P<0.05]. (2) Follicle development: the incidence of dominant follicles, rate of cumulative cycle ovulation, and rate of cumulative cycle mature follicle ovulation were significantly higher in the CM group than those in the placebo group [93.8% (350/373) vs. 89.5% (341/381), 80.4% (275/342) vs. 69.1% (253/366), 65.8% (181/275) vs 56.1% (142/253), P<0.05 or P<0.01]). The incidence of cumulative cycle luteinized unruptured follicle syndrome was significantly lower in the CM group than in the placebo group [11.7% (40/342) vs. 17.8% (65/366), P<0.05). (3) Endometrial receptivity: after treatment, both endometrial types and endometrial blood flow types in the CM group were mainly types A and B, while those in the placebo group were mainly types B and C, with a significant difference between the two groups (both P<0.05). (4) Adverse events: the incidence of adverse events between the two groups was not significantly different (P>0.05). CONCLUSION: Strategies for activating blood circulation-regulating Gan (Liver)-tonifying Shen (Kidney) sequential therapy can effectively improve the clinical pregnancy rate and live birth rate of endometriosis-associated infertility with qi stagnation and blood stasis after laparoscopy, improve follicular development, promote ovulation, improve endometrial receptivity, while being a safe treatment option. (Trial registration No. NCT02676713).


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Endometriose/cirurgia , Infertilidade Feminina/tratamento farmacológico , Infertilidade Feminina/cirurgia , Resultado da Gravidez , Adulto , Método Duplo-Cego , Endometriose/complicações , Feminino , Humanos , Infertilidade Feminina/etiologia , Medicina Tradicional Chinesa , Gravidez , Taxa de Gravidez
9.
Insect Biochem Mol Biol ; 97: 1-9, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29680288

RESUMO

In the tobacco hornworm Manduca sexta, juvenile hormone (JH) is critical for the control of species-specific size. However, whether the basic helix-loop-helix/Per-Arnt-Sim domain receptor methoprene-tolerant (Met) is involved remains unconfirmed. In the present paper, we found that RNA interference (RNAi)-aided knockdown of Met gene (LdMet) lowered the larval and pupal fresh weights and shortened the larval development period in the Colorado potato beetle Leptinotarsa decemlineata. Dietary introduction of JH into the LdMet RNAi larvae rescued neither the decreased weights nor the reduced development phase, even though JH ingestion by control larvae extended developmental time and caused large pupae. Moreover, the transcript levels of five genes involved in prothoracicotropic hormone and cap 'n' collar isoform C/Kelch-like ECH associated protein 1 pathways were upregulated in the LdMet silenced larvae. Ecdysteroidogenesis was thereby activated; 20-hydroxyecdysone (20E) titer was increased; and 20E signaling pathway was elicited in the LdMet RNAi larvae. Therefore, JH, acting through its receptor Met, inhibits PTTH production and release before the attainment of critical weight. Once the critical weight is reached, JH production and release are averted; and the hemolymph JH is removed. The elimination of JH allows the brain to release PTTH. PTTH subsequently stimulates ecdysteroid biosynthesis and release to start larval-pupal transition in L. decemlineata.


Assuntos
Tamanho Corporal/efeitos dos fármacos , Besouros/crescimento & desenvolvimento , Resistência a Medicamentos , Ecdisteroides/biossíntese , Metoprene/farmacologia , Animais , Larva/crescimento & desenvolvimento
10.
Medicine (Baltimore) ; 96(36): e8005, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28885364

RESUMO

BACKGROUND: The aim of this study was to compare the safety and survival outcomes of early stage cervical cancer patients treated by laparoscopically assisted radical vaginal hysterectomy (LARVH) versus abdominal radical hysterectomy (ARH). METHODS: Since March 2008 to July 2012, the patients with early stage cervical cancer undergoing LARVH or ARH in Beijing hospital have been entered into this study. Statistical analysis used Statistical Product and Service Solutions (SPSS) and significance was defined as P < .05. RESULT: Forty-two patients were included in LARVH group and 35 patients in ARH group. Both groups were similar with respect to age, body mass index (BMI), histological diagnosis, and stage. There were no differences in operative time, vaginal length, and postoperative complications, but blood loss, rate of transfusion, length of catheterized, and length of hospital stay were significantly less in LARVH. Number of lymph node retrieved was less than ARH. No differences were seen regarding recurrence rate, length of disease free survival, overall survival, and mortality rate after a median follow up of 58.5 and 48.5 months. CONCLUSION: LARVH is a suitable alternative to ARH for early-stage cervical cancer, which shows less blood loss, shorter catheterized and hospital stay, and similar survival outcomes.


Assuntos
Histerectomia/métodos , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Perda Sanguínea Cirúrgica , Transfusão de Sangue , Catéteres , Feminino , Seguimentos , Humanos , Laparoscopia , Tempo de Internação , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Duração da Cirurgia , Complicações Pós-Operatórias , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
11.
Plant Cell Rep ; 36(4): 529-542, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28155114

RESUMO

KEY MESSAGE: Over-expression of SlJA2 decreased the accumulation of SA, which resulted in significant physiological and gene expression changes in transgenic tobacco plants, leading to the decreased heat tolerance of transgenic tobacco. NAC family, the largest transcription factors in plants, responses to different environmental stimuli. Here, we isolated a typical NAC transcription factor (SlJA2) from tomato and got transgenic tobacco with SlJA2 over-expression. Expression of SlJA2 was induced by heat stress (42 °C), chilling stress (4 °C), drought stress, osmotic stress, abscisic acid, and salicylic acid. Over-expression of SlJA2 decreased the accumulation of salicylic acid by regulating expression of salicylic acid degradation gene under heat stress. Compared to WT plants, stomatal apertures and water loss increased in transgenic plants, and the damage of photosynthetic apparatus and chlorophyll breakdown were more serious in transgenic plants under heat stress. Meanwhile, more H2O2 and O2·- were accumulated transgenic plants and proline synthesis was restricted, which resulted in more serious oxidative damage compared to WT. qRT-PCR analysis showed that over-expression of SlJA2 could down-regulate genes involved in reactive oxygen species scavenging, proline biosynthesis, and response to heat stress. All the above results indicated that SlJA2 may be a negative regulator responded to plant's heat tolerance. Thus, this study provides new insight into roles of NAC family member in plant response to abiotic stress.


Assuntos
Expressão Gênica , Nicotiana/metabolismo , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Transdução de Sinais/genética , Estresse Fisiológico/genética , Termotolerância/genética , Secas , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Peróxido de Hidrogênio/metabolismo , Solanum lycopersicum/genética , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/efeitos dos fármacos , Plantas Geneticamente Modificadas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ácido Salicílico/farmacologia , Transdução de Sinais/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Nicotiana/efeitos dos fármacos , Nicotiana/genética
12.
Onco Targets Ther ; 9: 4397-409, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27499634

RESUMO

Lung cancer has become one of the leading causes of cancer mortality worldwide, and non-small-cell lung cancer (NSCLC) accounts for ~85% of all lung cancer cases. Currently, platinum-based chemotherapy drugs, including cisplatin and carboplatin, are the most effective treatment for NSCLC. However, the clinical efficacy of chemotherapy is markedly reduced later in the treatment because drug resistance develops during the treatment. Recently, a series of studies has suggested the involvement of FAT10 in the development and malignancy of multiple cancer types. In this study, we focused our research on the function of FAT10 in NSCLC, which has not been previously reported in the literature. We found that the expression levels of FAT10 were elevated in quick chemoresistance NSCLC tissues, and we demonstrated that FAT10 promotes NSCLC cell proliferation, migration, and invasion. Furthermore, the protein levels of FAT10 were elevated in cisplatin- and carboplatin-resistant NSCLC cells, and knockdown of FAT10 reduced the drug resistance of NSCLC cells. In addition, we gained evidence that FAT10 regulates NSCLC malignancy and drug resistance by modulating the activity of the nuclear factor kappa B signaling pathway.

13.
J Plant Physiol ; 204: 54-65, 2016 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-27518221

RESUMO

The NAC proteins are the largest transcription factors in plants. The functions of NACs are various and we focus on their roles in response to abiotic stress here. In our study, a typical NAC gene (SlNAM1) is isolated from tomato and its product is located in the nucleus. It also has a transcriptional activity region situated in C-terminal. The expression levels of SlNAM1 in tomato were induced by 4°C, PEG, NaCl, abscisic acid (ABA) and methyl jasmonate (MeJA) treatments. The function of SlNAM1 in response to chilling stress has been investigated. SlNAM1 overexpression in tobacco exhibited higher germination rates, minor wilting, and higher photosynthetic rates (Pn) under chilling stress. Meanwhile, overexpression of SlNAM1 improved the osmolytes contents and reduced the H2O2 and O2•- contents under low temperature, which contribute to alleviating the oxidative damage of cell membrane after chilling stress. Moreover, the transcripts of NtDREB1, NtP5CS, and NtERD10s were higher in transgenic tobacco, and those increased expressions may confer higher chilling tolerance of transgenic plants. These results indicated that overexpression of SlNAM1 could improve chilling stress tolerance of transgenic tobacco.


Assuntos
Adaptação Fisiológica , Temperatura Baixa , Nicotiana/fisiologia , Proteínas de Plantas/metabolismo , Solanum lycopersicum/metabolismo , Estresse Fisiológico , Fatores de Transcrição/metabolismo , Sequência de Aminoácidos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Peróxido de Hidrogênio/metabolismo , Malondialdeído/metabolismo , Estresse Oxidativo , Proteínas de Plantas/química , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Alinhamento de Sequência , Frações Subcelulares/metabolismo , Superóxidos/metabolismo , Nicotiana/genética , Nicotiana/crescimento & desenvolvimento , Fatores de Transcrição/química , Ativação Transcricional/genética , Regulação para Cima/genética
14.
Sci Rep ; 6: 26963, 2016 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-27377989

RESUMO

Previous investigations on photosynthesis have been performed on leaves irradiated from the adaxial surface. However, leaves usually sway because of wind. This action results in the alternating exposure of both the adaxial and abaxial surfaces to bright sunlight. To simulate adaxial and abaxial surfaces alternant irradiation (ad-ab-alt irradiation), the adaxial or abaxial surface of leaves were exposed to light regimes that fluctuated between 100 and 1,000 µmol m(-2) s(-1). Compared with constant adaxial irradiation, simulated ad-ab-alt irradiation suppressed net photosynthetic rate (Pn) and transpiration (E) but not water use efficiency. These suppressions were aggravated by an increase in alternant frequency of the light intensity. When leaves were transferred from constant light to simulated ad-ab-alt irradiation, the maximum Pn and E during the high light period decreased, but the rate of photosynthetic induction during this period remained constant. The sensitivity of photosynthetic gas exchange to simulated ad-ab-alt irradiation was lower on abaxial surface than adaxial surface. Under simulated ad-ab-alt irradiation, higher Pn and E were measured on abaxial surface compared with adaxial surface. Therefore, bifacial leaves can fix more carbon than leaves with two "sun-leaf-like" surfaces under ad-ab-alt irradiation. Photosynthetic research should be conducted under dynamic conditions that better mimic nature.


Assuntos
Dióxido de Carbono/metabolismo , Melia azedarach/metabolismo , Fotossíntese , Folhas de Planta/metabolismo , Solanum lycopersicum/metabolismo , Solanum lycopersicum/efeitos da radiação , Melia azedarach/efeitos da radiação , Folhas de Planta/efeitos da radiação , Estômatos de Plantas , Transpiração Vegetal , Luz Solar
15.
Drug Des Devel Ther ; 9: 3837-51, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26229444

RESUMO

The epidermal growth factor receptor (EGFR) family has been validated as a successful antitumor drug target for decades. Known EGFR inhibitors were exposed to distinct drug resistance against the various EGFR mutants within non-small-cell lung cancer (NSCLC), particularly the T790M mutation. Although so far a number of studies have been reported on the development of third-generation EGFR inhibitors for overcoming the resistance issue, the design procedure largely depends on the intuition of medicinal chemists. Here we retrospectively make a detailed analysis of the 42 EGFR family protein crystal complexes deposited in the Protein Data Bank (PDB). Based on the analysis of inhibitor binding modes in the kinase catalytic cleft, we identified a potent EGFR inhibitor (compound A-10) against drug-resistant EGFR through fragment-based drug design. This compound showed at least 30-fold more potency against EGFR T790M than the two control molecules erlotinib and gefitinib in vitro. Moreover, it could exhibit potent HER2 inhibitory activities as well as tumor growth inhibitory activity. Molecular docking studies revealed a structural basis for the increased potency and mutant selectivity of this compound. Compound A-10 may be selected as a promising candidate in further preclinical studies. In addition, our findings could provide a powerful strategy to identify novel selective kinase inhibitors on the basis of detailed kinase-ligand interaction space in the PDB.


Assuntos
Antineoplásicos/farmacologia , Desenho de Fármacos , Receptores ErbB/antagonistas & inibidores , Simulação de Acoplamento Molecular , Receptores ErbB/genética , Cloridrato de Erlotinib/farmacologia , Gefitinibe , Humanos , Quinazolinas/farmacologia , Receptor ErbB-2/antagonistas & inibidores , Estudos Retrospectivos
16.
Asian Pac J Cancer Prev ; 16(18): 8031-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26745035

RESUMO

BACKGROUND: Preclinical studies have demonstrated that ß-adrenergic receptor antagonists could improve the prognosis of breast cancer. However, the conclusions of clinical and pharmacoepidemiological studies have been inconsistent. This review was conducted to re-assess the relationship between beta-adrenoceptor blockers and breast cancer prognosis. MATERIALS AND METHODS: The literature was searched from PubMed, EMBASE and Web of Nature (Thompson Reuters) databases through using key terms, such as breast cancer and beta- adrenoceptor blockers. RESULTS: Ten publications met the inclusion criteria. Six suggested that receiving beta- adrenoceptor blockers reduced the risk of breast cancer-specific mortality, and three of them had statistical significance (hazard ratio (HR)=0.42; 95% CI=0.18-0.97; p=0.042). Two studies reported that risk of recurrence and distant metastasis (DM) were both significantly reduced. One study demonstrated that the risk of relapse- free survival (RFS) was raised significantly with beta-blockers (BBS) (HR= 0.30; 95% CI=0.10-0.87; p=0.027). One reported longer disease-free interval (Log Rank (LR)=6.658; p=0.011) in BBS users, but there was no significant association between overall survival (OS) and BBS (HR= 0.35; 95% CI=0.12-1.0; p=0.05) in five studies. CONCLUSIONS: Through careful consideration, it is suggested that beta-adrenoceptor blockers use may be associated with improved prognosis in breast cancer patients. Nevertheless, larger size studies are needed to further explore the relationship between beta-blocker drug use and breast cancer prognosis.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptores Adrenérgicos beta/química , Animais , Feminino , Humanos
17.
Plant Physiol Biochem ; 80: 318-27, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24852818

RESUMO

Chilling is one of the most serious environmental stresses that disrupt the metabolic balance of cells and enhance the production of reactive oxygen species (ROS). Light harvesting complex (LHC) proteins had a function in dissipating excess excitation energy and eliminating ROS to maintain the normal physiological function of cells. A tomato (Lycopersicon esculentum) LHC antenna protein gene (LeLhcb2) was isolated. The LeLhcb2-green fluorescent protein (GFP) fusion protein was targeted to the chloroplast of Arabidopsis mesophyll protoplast. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that the expression of LeLhcb2 was markedly abundant in leaves and was induced by chilling (4 °C). qRT-PCR analysis and western blot confirmed that the sense gene LeLhcb2 was transferred into tobacco genome and overexpressed. Under chilling stress, the transgenic plants showed not only better growth, higher fresh weight, chlorophyll content, but also lower malondialdehyde (MDA) accumulation and relative electrical conductivity (REC), compared with the wild type (WT). The maximal photochemical efficiency of PSII (Fv/Fm), non-photochemical quenching (NPQ) and D1 protein content were also higher in the transgenic plants. Furthermore, the relatively lower hydrogen peroxide (H2O2) and superoxide radical (O2(-)) levels in the sense plants were not considered to due to the higher activity of ascorbate peroxidase (APX) and superoxide dismutase (SOD). These results suggested that the overexpression of LeLhcb2 had a key function in alleviating photo-oxidation of PSII and enhanced transgenic tobacco tolerance to chilling stress.


Assuntos
Nicotiana/metabolismo , Nicotiana/fisiologia , Plantas Geneticamente Modificadas/metabolismo , Plantas Geneticamente Modificadas/fisiologia , Solanum lycopersicum/genética , Temperatura Baixa , Complexos de Proteínas Captadores de Luz/metabolismo , Plantas Geneticamente Modificadas/genética , Espécies Reativas de Oxigênio/metabolismo , Nicotiana/genética
18.
Plant Physiol Biochem ; 73: 309-20, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24184451

RESUMO

ICE1 (inducer of CBF expression 1), a MYC-type bHLH transcription factor, is an important activator of CBF3/DREB1A for regulating cold signaling and stress tolerance. In this study, we isolated the novel ICE1-like gene SlICE1a from tomato which contains the conserved bHLH domain, an S-rich motif, and ACT-domain. It is localized in the nucleus and harbors transcription-activating activity in the N-terminal. In addition, the SlICE1a transcript is slightly upregulated by cold stress, salt stress, and osmotic stress. SlICE1a overexpression in tobacco enhances the induction of CBF/DREB and their target genes, consequently increasing the levels of proline, soluble sugars, and late embryogenesis abundant (LEA) proteins, and enhancing tolerance to cold stress, osmotic stress, and salt stress. SlICE1a functions in abiotic stress responses by regulating the expression of stress-tolerant genes, and is thus beneficial for crop improvement.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Temperatura Baixa , Regulação da Expressão Gênica de Plantas , Nicotiana/genética , Pressão Osmótica , Tolerância ao Sal/genética , Solanum lycopersicum/genética , Adaptação Fisiológica/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Metabolismo dos Carboidratos , Genes de Plantas , Solanum lycopersicum/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Prolina/metabolismo , Estresse Fisiológico/genética , Nicotiana/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
19.
J Zhejiang Univ Sci B ; 14(7): 578-85, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23825143

RESUMO

Ascorbate peroxidases are directly involved in reactive oxygen species (ROS) scavenging by reducing hydrogen peroxide to water. The tomato thylakoid-bound ascorbate peroxidase gene (StAPX) was introduced into tobacco. RNA gel blot analysis confirmed that StAPX in tomato leaves was induced by methylviologen-mediated oxidative stress. The sense transgenic seedlings exhibited higher tAPX activity than that of the wild type (WT) plants under oxidative stress conditions, while the antisense seedlings exhibited lower tAPX activity. Lower APX activities of antisense transgenic seedlings caused higher malondialdehyde contents and relative electrical conductivity. The sense transgenic seedlings with higher tAPX activity maintained higher chlorophyll content and showed the importance of tAPX in maintaining the optimal chloroplast development under methylviologen stress conditions, whereas the antisense lines maintained lower chlorophyll content than WT seedlings. Results indicated that the over-expression of StAPX enhanced tolerance to methylviologen-mediated oxidative stress in sense transgenic tobacco early seedlings, whereas the suppression of StAPX in antisense transgenic seedlings showed high sensitivity to oxidative stress.


Assuntos
Ascorbato Peroxidases/biossíntese , Ascorbato Peroxidases/genética , Regulação da Expressão Gênica de Plantas , Nicotiana/fisiologia , Estresse Oxidativo , Paraquat/química , Antioxidantes/química , Clorofila/química , Cloroplastos/genética , Condutividade Elétrica , Herbicidas/química , Solanum lycopersicum/enzimologia , Malondialdeído/química , Oligonucleotídeos Antissenso/genética , Fenótipo , Plantas Geneticamente Modificadas/genética , Plântula/genética , Estresse Fisiológico , Nicotiana/genética
20.
Plant Physiol Biochem ; 70: 150-8, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23777904

RESUMO

The salt overly sensitive pathway has an important function in plant salinity tolerance. The enhancer of SOS3-1 (ENH1) participates in a new salinity stress pathway with SOS2 but without SOS3. To investigate the physiological effects and functional mechanism of ENH1 under salt stress, ENH1 was isolated from tomato and overexpressed in tobacco. Under salt stress, the sprouting percentage, fresh weight, and dry weight of transgenic plants were higher than those of wild-type (WT) plants. Under salt stress, the chlorophyll content, net photosynthetic rate, and maximal photochemical efficiency of PSII in transgenic plants decreased more slowly than those in WT plants. The overexpression of LeENH1 in tobacco excluded Na(+) from the cytosol and retained high K(+) levels in the cytosol to reestablish ion homeostasis. Higher thylakoid-bound ascorbate peroxidase activity and lower reactive oxygen species levels were found in transgenic plants under salt stress.


Assuntos
Citosol/metabolismo , Nicotiana/metabolismo , Proteínas de Plantas/metabolismo , Tolerância ao Sal/genética , Sódio/metabolismo , Solanum lycopersicum/metabolismo , Estresse Fisiológico/genética , Ascorbato Peroxidases/metabolismo , Clorofila/genética , Clorofila/metabolismo , Expressão Gênica , Genes de Plantas , Homeostase , Solanum lycopersicum/genética , Solanum lycopersicum/fisiologia , Fotossíntese/genética , Complexo de Proteína do Fotossistema II/genética , Complexo de Proteína do Fotossistema II/metabolismo , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Potássio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Tilacoides/metabolismo , Nicotiana/genética
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