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1.
Endocr Pathol ; 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31788765

RESUMO

Napsin A is widely used in the diagnosis of lung adenocarcinoma and has also been reported to be positive in cases of thyroid carcinomas. We investigated napsin A levels through immunohistochemistry on whole sections of 210 primary thyroid tumors of various subtypes and another 41 metastatic thyroid carcinomas, and compared these with 125 primary and 25 metastatic lung adenocarcinomas. The results showed that napsin A was expressed in 23.8% thyroid tumors and 30.3% papillary thyroid carcinomas. Most cases showed a focal and weak to moderate expression. In comparison, 80.8% primary lung adenocarcinomas expressed napsin A, with mostly diffused and strong expression. For metastatic carcinomas of thyroid and lung origin, napsin A was detected in 39.0% of thyroid carcinomas in contrast to 88.0% in cases of lung adenocarcinomas. Comparisons of additional markers, TTF-1, CK7, thyroglobulin, and Pax-8 in metastatic carcinomas showed the overlapping expression of immunomarkers of TTF-1 and CK7. Thyroglobulin and Pax-8 were useful for distinguishing between metastatic carcinomas; however, Pax-8 may be a superior marker due to its higher sensitivity. The clinicopathological analysis of papillary thyroid carcinomas showed that the expression of napsin A was positively correlated with lymph node metastasis (p = 0.030). Here, we focused on the expression of napsin A in thyroid tumors and compared it with that in lung adenocarcinomas. The expression of napsin A is common in thyroid tumors and the combined expression of napsin A and TTF-1 in a metastatic thyroid carcinoma is a cause for concern due to chances of misdiagnosis as lung adenocarcinoma.

2.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(4): 609-614, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31642244

RESUMO

OBJECTIVE: To investigate the effects of individualized intervention on postpartum breast-feeding behavior and satisfaction after cesarean section (CS). METHODS: 341 pregnant women who had cesarean section in West China Second Hospital of Sichuan University from 1st July to 30th August in 2018 were randomly divided into intervention group (171 cases) and control group (170 cases). The participants in experimental group received individualized intervention through the combination of prenatal and postnatal. The participants in control group received routine nursing care. The basic clinical data and breastfeeding information at discharge and day 42 postpartum were compared between the two groups. RESULTS: There were no significant differences in age, ethnicity, anesthesia type, preoperative feeding time between the two groups (P>0.05). At the time of discharge and day 42 postpartum, the rate of exclusive breastfeeding, breastfeeding satisfaction and planned breastfeeding duration in the intervention group were higher than those in the control group (P < 0.05). The incidence and degree of breast distending pain, the incidence of cracked nipples, the times of adding formula milk in 24 h, the rate of using feeding bottle and the incidence of feeding problems were all higher in the control group than those in the intervention group (P < 0.05). The knowledge scores of breastfeeding in both groups were higher at discharge than at admission, and the score was higher in the intervention group than that in the control group at the time of discharge. CONCLUSION: The combination of prenatal and postnatal individualized intervention can significantly improve the knowledge, behavior and satisfaction of breastfeeding.


Assuntos
Aleitamento Materno , Cesárea , Cuidado Pós-Natal , Cuidado Pré-Natal , China , Feminino , Humanos , Satisfação do Paciente , Período Pós-Parto , Gravidez
3.
Environ Sci Pollut Res Int ; 26(33): 34622-34632, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31654308

RESUMO

Organophosphorus pesticides are effective, cheap, and used extensively but can harm aquatic organism and human health. Here, water quality criteria (WQCs) for dichlorvos (DDVP) and malathion (MAL) were derived. Nine aquatic organisms native to China were used in toxicity tests. Published toxicity data for aquatic organisms native and non-native to China were also analyzed. DDVP and MAL WQCs were derived using (log-normal model) species sensitivity distributions. Species sensitivity distribution curves indicated native and non-native species have different sensitivities to DDVP. The sensitivities of native and non-native species to MAL were not different because non-native species data for fewer than eight genera were available, so further research is required. The results indicated that native species need to be considered when deriving WQCs. The criteria maximum concentration (CMC) and criteria continuous concentration (CCC) were 1.33 and 0.132 µg/L, respectively, for DDVP, and 0.100 and 0.008 µg/L, respectively, for MAL. The CMCs for DDVP and MAL derived using ETX 2.0 software and species sensitivity ranks were different from the CMCs obtained using the SSD method because of parameter uncertainties. The DDVP and MAL WQCs were significantly lower than Chinese surface water quality standard thresholds. The results provide basic data for revising these thresholds.

4.
Clin Exp Rheumatol ; 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31573475

RESUMO

OBJECTIVES: As a rare systemic autoinflammatory disease, adult-onset Still's disease (AOSD) has heterogeneous clinical manifestations, response to treatment and outcome. This study tried to assess the clinical characteristics, laboratory tests, and treatments of Chinese AOSD patients, and make a retrospective analysis. METHODS: We collected from 7 hospitals in China a total of 517 Chinese patients with AOSD who satisfied the Yamaguchi criteria. We retrospectively evaluated their clinical features, laboratory tests, treatments and compared them with published data from different studies. All the data in this study were from medical records and further statistic analyses. RESULTS: We evaluated a total of 517 AOSD patients, 72% female, average age of onset was 37.7; spiking fever, rash and arthralgia occurred in 472 (91.3%), 413 (79.9%), 378 (73.1%) cases, respectively. There were 439/513 (85.6%) cases with leukocytosis and 456/476 (95.8%) cases with raised serum ferritin. The highest frequently used medications and regimens for remission were glucocorticoids (498/517, 96.3%), methotrexate (273/517, 52.8%) and hydroxychloroquine (174/517, 33.7%). 84.4%. 357/423 of AOSD cases were able to achieve initial remission with different regimens, mostly including glucocorticoids, methotrexate or hydroxychloroquine. 47.2% of them (244/517) received 30

6.
Appl Microbiol Biotechnol ; 103(20): 8497-8509, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31501938

RESUMO

Unlike eukaryotes, prokaryotes are less proficient in homologous recombination (HR) and non-homologous end-joining (NHEJ). All existing genomic editing methods for Escherichia coli (E. coli) rely on exogenous HR or NHEJ systems to repair DNA double-strand breaks (DSBs). Although an E. coli native end-joining (ENEJ) system has been reported, its potential in genetic engineering has not yet been explored. Here, we present a CRISPR-Cas9-assisted native end-joining editing and show that ENEJ-dependent DNA repair can be used to conduct rapid and efficient deletion of chromosome fragments up to 83 kb or gene inactivation. Moreover, the positive rate and editing efficiency are independent of high-efficiency competent cells. The method requires neither exogenous DNA repair systems nor introduced editing template. The Cas9-sgRNA complex is the only foreign element in this method. This study is the first successful engineering effort to utilize ENEJ mechanism in genomic editing and provides an effective strategy for genetic engineering in bacteria that are inefficient in HR and NHEJ.

7.
J Biomol Struct Dyn ; : 1-19, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31556349

RESUMO

The therapeutic potential of PPARs antagonists extends beyond diabetes. PPARs antagonists represent a new drug class that holds promise as a broadly applicable therapeutic approach for cancer treatment. Thus, there is a strong need to develop a rational design strategy for creating PPARs antagonists. In this study, three-dimensional quantitative structure-activity relationship (3D-QSAR) models of PPARα receptor (CoMFA-1, q2 = 0.636, r2 = 0.953; CoMSIA-1, q2 = 0.779, r2 = 0.999) and PPARδ receptor (CoMFA-2, q2 = 0.624, r2 = 0.906; CoMSIA-2, q2 = 0.627, r2 = 0.959) were successfully constructed using 35 triazolone ring derivatives. Contour map analysis revealed that the electrostatic and hydrophobic fields played vital roles in the bioactivity of dual antagonists. Molecular docking studies suggested that the hydrogen bonding, electrostatic and hydrophobic interactions all influenced the binding of receptor-ligand complex. Based on the information obtained above, we designed a series of compounds. The docking results were mutually validated with 3D-QSAR results. Three-dimensional-QSAR and absorption, distribution, metabolism, excretion and toxicity (ADMET) predictions indicated that 19 newly designed compounds possessed excellent biological activity and physicochemical properties. In summary, this research could provide theoretical guidance for the structural optimization of novel PPARα and δ dual antagonists. Communicated by Ramaswamy H. Sarma.

8.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(6): 684-688, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31315723

RESUMO

OBJECTIVE: To analyze the characteristics of cellular immune function and its prognostic risk factors in patients with community-acquired pneumonia (CAP). METHODS: The clinical data of patients diagnosed as CAP admitted to department of respiratory and critical care medicine of the Second Affiliated Hospital of Anhui Medical University from June 2018 to February 2019 were retrospectively analyzed. The patients were divided into survival group and death group according to the mortality at discharge and 28-day survival after hospital discharge; in addition, they were divided into bacterial group, fungi group and mixed infection group according to pathogen results at discharge. The differences of general clinical characteristics, arterial blood gas analysis indexes, plasma albumin, cellular immune function, inflammatory cytokines, the length of hospital stay among groups were analyzed. The correlation between the prognosis-related indicators in patients were analyzed by Pearson test or Spearman test, and Logistic regression model was used to analyze the risk factors of patients in non-survival group. RESULTS: 106 patients were finally enrolled, 69 of whom were survived, and 37 dead. Among 56 patients with pathogen results, 27 were diagnosed as bacterial infection, 11 as fungal infection, and 18 with mixed infection. Compared with the survival group, plasma albumin level, total T cell count, CD4+T cell count, CD8+T cell count were decreased in the death group, temperature, pH, acute physiology and chronic health evaluation II (APACHE II), procalcitonin (PCT), interleukin-6 (IL-6), C-reactive protein (CRP) were increased, and the length of hospital stay was significantly shortened. While there was no significant difference in gender, age, mean arterial pressure, arterial oxygen pressure, CD4+/CD8+, regulation T cell/effect T cell (TREG/TEF) between the two groups. Correlation analysis showed that plasma albumin, the length of hospital stay, APACHE II score, CD4+T cell count, CD8+T cell count, CD4+/CD8+, PCT, IL-6, CRP were correlated with death (r value was -0.480, -0.209, 0.203, -0.279, -0.270, 0.271, 0.247, 0.410, 0.329, all P < 0.05). Logistic regression analysis showed that plasma albumin, CD4+T cell count, CD8+T cell count, CD4+/CD8+decreased; APACHE II score, PCT, IL-6, and CRP increased; the length of hospital stay were correlated with death, and all were independent risk factors for death in CAP patients (all P < 0.05). Correlation analysis showed that the APACHE II score was negatively related to plasma albumin (r = -0.375, P < 0.05), positively related to CRP and IL-6 (r value was 0.363 and 0.333 respectively, both P < 0.05); negative correlation between plasma albumin and IL-6 (r = -0.372, P < 0.05), PCT and CD4+T cell count (r = -0.354, P < 0.05), CRP and the length of hospital stay (r = -0.356, P < 0.05). There were no significant correlations between the others. There was no significant difference in cellular immune function or inflammatory factor expression between different pathogenic infections. CONCLUSIONS: Cellular immune dysfunction, hypoproteinemia, APACHE II score and elevated inflammatory index are all influential factors for the death of CAP patients. Apart from conventional anti-infective treatment, the symptoms of hypoproteinemia and cellular immune function can predict the severity and prognosis of CAP patients.


Assuntos
Infecções Comunitárias Adquiridas/imunologia , Imunidade Celular/fisiologia , Pneumonia/imunologia , APACHE , Humanos , Prognóstico , Estudos Retrospectivos , Fatores de Risco
9.
Int J Mol Med ; 44(2): 405-416, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173173

RESUMO

Hydroxysafflor Yellow A (HSYA) may reduce ischemia/reperfusion (I/R) injury. However, the underlying molecular mechanisms remain unclear. The present study explored the effect and the mechanisms of HSYA on myocardial injury in vivo and in vitro. Myocardial infarct size was assessed by Evans blue/2,3,5­triphenyltetrazoliumchloride staining. Levels of cardiac troponin I (cTnI), interleukin­6 (IL­6), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured using commercial kits. Alteration of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) generation was determined by fluorescent signals. Apoptosis was detected by terminal deoxynucleotidyl­transferase­mediated dUTP nick­end labeling staining, flow cytometry assay and caspase­3 activity. Expression levels of the apoptosis­associated proteins were detected by reverse transcription quantitative polymerase chain reaction and western blot analysis. In vivo, animals treated with HSYA presented less severe myocardial injury and decreased janus kinase 2 (JAK2)/signal transducer and activator of transcription 1 (STAT1) activity, improved antioxidant capacity and decreased apoptosis. In vitro, compared with the hypoxia (H)/reoxygenation (R) + HSYA group, AG490 and S1491 treatment decreased the releases of cTnI, IL­6 and LDH and enhanced the resistance to oxidative stress by maintaining MMP and decreasing ROS generation. In addition, AG490 and S1491 were also identified to alleviate the H/R­induced apoptosis by inhibiting caspase 3 activity and modulating the expression levels of cleaved caspase­3, tumor necrosis factor receptor superfamily member 6 (Fas), Fas ligand, B­cell lymphoma 2 (Bcl­2) and Bcl­2­associated X protein. These data suggested that inactivation of the JAK2/STAT1 pathway strengthened the HSYA­induced protective effect in H/R­induced myocardial injury. In conclusion, the treatment of HSYA was effective in decreasing IR­induced myocardial injury, and this may be largely dependent on the JAK2/STAT1 pathway. Therefore, the present study provided a potential strategy to prevent myocardial I/R injury.

10.
Cancer Biol Ther ; 20(8): 1091-1096, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30991882

RESUMO

Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare malignant tumor defined by a unique chromosomal translocation of the NUT gene on chromosome 15q14. This very rare tumor is usually located in midline structures, especially in the head and neck region. However, there have been no previous reports of NMC arising from the eyes. Here, we first describe a case of NMC originating in the right orbit of a 60-year-old woman. A multimodality approach, including surgery, chemotherapy, radiotherapy, and target therapy, was adopted in clinical practice.

11.
Opt Lett ; 44(6): 1524-1527, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30874692

RESUMO

Cascading of the electro-optic (EO) effect and nonlinear wave mixing can provide a way to manipulate photonic conversion in an electrically controllable manner. Here we experimentally demonstrate simultaneous transverse EO coupling and second-harmonic generation (SHG) in a periodically poled lithium niobate on insulator ridge waveguide. With tight light confinement, large EO, and nonlinear coefficients in the LNOI waveguide, the integrated device features a low-voltage fast-speed response for EO coupling and efficient conversion for SHG. The proposed scheme holds promise in realizing electrically controllable on-chip nonlinear devices.

12.
Medicine (Baltimore) ; 97(43): e12920, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30412096

RESUMO

To explore the influence of the 75 g oral glucose tolerance test (OGTT) on pregnancy outcomes and to determine the risk factors for adverse outcomes among women with gestational diabetes mellitus (GDM).This retrospective cohort study was conducted among women who had GDM and were treated between January 1, 2015 and December 31, 2017. The diagnostic criteria for GDM were proposed by the International Diabetes and Pregnancy Research Organization (IADPSG) in 2010. Women with GDM were stratified according to the number of abnormal OGTT values or the presence/absence of adverse pregnancy outcomes. Maternal characteristics, OGTT values, pregnancy outcomes, and the relationship between the latter 2 were analyzed.In total, 3221 pregnant women with GDM were included. The incidence of adverse outcomes was affected by maternal age (28-37 years, in particular; odds ratio [OR], 1.403; 95% confidence interval [CI], 1.037-1.899; P = .028), days of pregnancy (OR, 0.904; 95% CI, 0.894-0.914; P < .001), gestational weight gain (OR, 1.018; 95% CI, 1.000-1.036;, P = .048), and age of menarche (OR, 0.925; 95% CI, 0.863-0.992; P = .029). Both fasting plasma glucose (FPG) and 2-h OGTT were positively correlated with adverse outcomes, of which FPG was more predictive (FPG: OR, 1.143; 95% CI, 1.007-1.297; P = .038; 2-h OGTT: OR, 1.074; 95% CI, 1.018-1.133; P = .009). Meanwhile, higher abnormal OGTT values were associated with significantly increased risks of antenatal insulin treatment, cesarean delivery, premature delivery, gestational hypertension, premature rupture of membranes, preeclampsia, macrosomia, neonatal asphyxia, and full term low weight infants.OGTT values and the number of abnormal glucose are associated with various adverse pregnancy outcomes. Stratified management is recommended for pregnant women with GDM, especially those with fasting hyperglycemia and/or 3 abnormal OGTT values.


Assuntos
Glicemia/análise , Diabetes Gestacional/epidemiologia , Jejum/sangue , Resultado da Gravidez/epidemiologia , Adulto , China/epidemiologia , Estudos de Coortes , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Feminino , Teste de Tolerância a Glucose/métodos , Teste de Tolerância a Glucose/estatística & dados numéricos , Humanos , Incidência , Gravidez , Complicações na Gravidez/epidemiologia , Estudos Retrospectivos , Fatores de Risco
13.
Histopathology ; 2018 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-30368884

RESUMO

AIMS: To assess the expression of EMT regulators in follicular thyroid tumours. METHODS AND RESULTS: The expression of E-cadherin (E-CAD) and transcription factors TWIST, SLUG, and SNAIL in follicular thyroid tumours were examined by immunohistochemistry in tissue samples, including 18 follicular adenomas (FA), 12 minimally invasive follicular thyroid carcinomas (MI-FTC), 16 widely invasive follicular thyroid carcinomas (WI-FTC), 10 poorly differentiated follicular thyroid carcinomas (PDTC), and 6 anaplastic thyroid carcinomas (ATC). Metastatic tumour tissues from 6 of these cases were also examined. The results showed an increasing expression trend of EMT regulators in a panel of follicular tumour cases with a spectrum of morphological subtypes from low risk to high risk malignancy. The expression of EMT regulators was higher in the WI-FTC, PDTC, and ATC groups but focal and lower in the FA and MI-FTC groups. Different expression intensity of E-CAD and EMT regulators at the tumour center part and the invasive front (IF) was observed. The loss of E-CAD and expression of EMT regulators were significantly correlated with distant metastasis and vascular invasion (VI) in the well-differentiated follicular carcinoma (WD-FTC), and 6 tumours of metastatic sites also showed variables positive for EMT regulators. The disease-free survival analysis showed an apparent relationship between the expression of EMT regulators and the tumour disease-free outcomes in WD-FTC. CONCLUSIONS: Our study supported the role of EMT in the development of follicular thyroid carcinoma and indicated that EMT regulatory proteins may play an important role in WD-FTC that are widely invasive, and exhibit distant metastasis. This article is protected by copyright. All rights reserved.

14.
Nat Commun ; 9(1): 3616, 2018 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-30190534

RESUMO

The translation of rare codons relies on their corresponding rare tRNAs, which could not be fully charged under amino acid starvation. Theoretically, disrupted or retarded translation caused by the lack of charged rare tRNAs can be partially restored by feeding or intracellular synthesis of the corresponding amino acids. Inspired by this assumption, we develop a screening or selection system for obtaining overproducers of a target amino acid by replacing its common codons with the corresponding synonymous rare alternative in the coding sequence of selected reporter proteins or antibiotic-resistant markers. Results show that integration of rare codons can inhibit gene translations in a frequency-dependent manner. As a proof-of-concept, Escherichia coli strains overproducing L-leucine, L-arginine or L-serine are successfully selected from random mutation libraries. The system is also applied to Corynebacterium glutamicum to screen out L-arginine overproducers. This strategy sheds new light on obtaining and understanding amino acid overproduction strains.

15.
Opt Express ; 26(9): 12016-12021, 2018 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-29716118

RESUMO

Configurable narrow bandwidth filters are indispensable components in optical communication networks. Here, we present an easily-integrated compact tunable filtering based on polarization-coupling process in a thin periodically poled lithium niobate (PPLN) in a reflective geometry via the transverse electro-optic (EO) effect. The structure, composed of an in-line polarizer and a thinned PPLN chip, forms a phase-shift Solc-type filter with similar mechanism to defected Bragg gratings. The filtering effect can be dynamically switched on and off by a transverse electric filed. Analogy of electromagnetically induced transparency (EIT) transmission spectrum and electrically controllable group delay is experimentally observed. The mechanism features tunable center wavelength in a wide range with respect to temperature and tunable optical delay to the applied voltage, which may offer another way for optical tunable filters or delay lines.

16.
Biochem Biophys Res Commun ; 498(1): 132-138, 2018 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-29425820

RESUMO

Emerging evidence has indicated that transforming growth factor-beta 1 (TGF-ß1) induces the epithelial-mesenchymal transition (EMT) in cancer cells, thus promoting their motility and invasiveness. Quercetin, a member of the polyphenolic flavonoid family, has been reported to display anticancer activity against a broad range of cancer cell types. Indeed, numerous studies have shown the cancer preventive effects and molecular mechanisms of quercetin in vitro using diverse cell model systems. However, the potential effect of quercetin on EMT remains unclear. In this study, we identified a unique function of quercetin in inhibiting the EMT process induced by TGF-ß1. In particular, quercetin rescued the morphological changes and EMT-like phenotypes in TGF-ß1-activated SW480 cells, and this inhibition of TGF-ß1-induced EMT was mediated via the suppression of Twist1 expression. In addition, quercetin strongly suppressed TGF-ß1-induced invasion of SW480 cells. Thus, quercetin may be considered a novel therapeutic agent for the treatment of patients with refractory cancer and for the prevention of the metastatic cascade initiated by EMT.


Assuntos
Caderinas/genética , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Proteínas Nucleares/metabolismo , Quercetina/farmacologia , Fator de Crescimento Transformador beta1/efeitos adversos , Proteína 1 Relacionada a Twist/metabolismo , Antígenos CD , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Metástase Neoplásica , Proteínas Nucleares/genética , Regiões Promotoras Genéticas/genética , Proteína 1 Relacionada a Twist/genética
17.
Acta Biomater ; 62: 257-272, 2017 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-28859899

RESUMO

In this study, novel prodrug-modified cationic liposome nanocomplexes (Combo NCs) were reported for gemcitabine (GEM) and docetaxel (DTX) co-delivery. This nanoplatform exhibited multiple favorable characteristics, such as a 'green' fabrication with a one-step chemical reaction, appropriate size (∼200nm) and distribution (PDI<0.2), low zeta potential (-31.1mv), high drug-loading efficiency (9.3% GEM plus 3.1% DTX, wt%) and pH and enzymatic dual-stimulus-responsive release properties. Immunofluorescence and cellular uptake studies showed that Combo NCs efficiently targeted overexpressed CD44 in MDA-MB-231 carcinoma. In vitro studies revealed that Combo NCs played a critical role in the synergistic induction of cytotoxicity, apoptosis and inhibition of wound healing. Combo NCs were confirmed to exhibit great potency for increasing S phase arrest and remodeling the CDA and dCK balance by decreasing the mRNA expression of CDA down to 0.09-fold and increasing the mRNA expression of dCK by 1.36-fold, remarkably increasing the dCK/CDA ratio to 15.3-fold compared with the blank control. The biodistribution results obtained in vivo revealed an effective accumulation in tumor foci. All of these advantages of Combo NCs contributed to their remarkable anti-tumor efficacy without systemic toxicity as well as their apoptosis-enhancing and anti-proliferative capacities, as determined by TUNEL and Ki67 immunohistochemistry in vivo. Consequently, such a rationally contemplated co-delivery system demonstrated the promising potential of clinical applications for triple-negative breast cancer therapy. STATE OF SIGNIFICANCE: The Combo NCs were innovatively applied for co-delivery of hydrophilic GEM and hydrophobic DTX. The ester bond linking and shielding effect of HA-GEM made the carriers achieve synchronous release properties, which was determined in in vitro release study. Due to the HA modification, the vectors own great potency for positive targeting to CD44 overexpressed triple-negative breast cancer cells MDA-MB-231. Cytotoxicity and apoptosis studies confirmed the targeting effect and synergism between two drugs. Interestingly, we found in cell cycle study, drug combinations (free combination or Combo NCs) didn't show a rise in G2M phase, which was significantly higher when treated DTX alone. We further discovered the role of DTX in combinations may involve in modulating GEM associated enzymes thus enhancing the efficacy of GEM. Consequently, this nanoplatform provided a novel solution for achieving targeted co-delivery and potentiating effect in cancer therapy.


Assuntos
Antígenos de Neoplasias/biossíntese , Protocolos de Quimioterapia Combinada Antineoplásica , Receptores de Hialuronatos/biossíntese , Nanoestruturas , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/química , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Desoxicitidina/análogos & derivados , Desoxicitidina/química , Desoxicitidina/farmacologia , Docetaxel , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Lipossomos , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Taxoides/química , Taxoides/farmacologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
18.
Neurotoxicology ; 59: 56-64, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28099871

RESUMO

Fluoride and arsenic are inorganic contaminants that occur in the natural environment. Chronic fluoride and/or arsenic exposure can induce developmental neurotoxicity and negatively influence intelligence in children, although the underlying molecular mechanisms are poorly understood. This study explored the effects of fluoride and arsenic exposure in drinking water on spatial learning, memory and key protein expression in the ERK/CREB signaling pathway in hippocampal and cerebral cortex tissue in rat offspring. Pregnant rats were divided into four groups. Control rats drank tap water, while rats in the three exposure groups drank water with sodium fluoride (100mg/L), sodium arsenite (75mg/L), and a sodium fluoride (100mg/L) and sodium arsenite (75mg/L) combination during gestation and lactation. After weaning, rat pups drank the same solution as their mothers. Spatial learning and memory ability of pups at postnatal day 21 (PND21) and postnatal day 42 (PND42) were measured using a Morris water maze. ERK, phospho-ERK (p-ERK), CREB and phospho-CREB (p-CREB) protein expression in the hippocampus and cerebral cortex was detected using Western blot. Compared with the control pups, escape latencies increased in PND42 pups exposed to arsenic and co-exposed to fluoride and arsenic, and the short-term and long-term spatial memory ability declined in pups exposed to fluoride and arsenic, both alone and in combination. Compared with controls, ERK and p-ERK levels decreased in the hippocampus and cerebral cortex in pups exposed to combined fluoride and arsenic. CREB protein expression in the cerebral cortex decreased in pups exposed to fluoride, arsenic, and the fluoride and arsenic combination. p-CREB protein expression in both the hippocampus and cerebral cortex was decreased in pups exposed to fluoride and arsenic in combination compared to the control group. There were negative correlation between the proteins expression and escape latency periods in pups. These data indicate that exposure to fluoride and arsenic in early life stage changes ERK, p-ERK, CREB and p-CREB protein expression in the hippocampus and cerebral cortex of rat offspring at PND21 and PND 42, which may contribute to impaired neurodevelopment following exposure.


Assuntos
Arsênico/toxicidade , Cariostáticos/toxicidade , Fluoretos/toxicidade , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Fatores Etários , Animais , Peso Corporal/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/embriologia , Hipocampo/crescimento & desenvolvimento , Hipocampo/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Ratos Sprague-Dawley , Reflexo/efeitos dos fármacos
19.
Front Plant Sci ; 8: 2256, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29403511

RESUMO

Plants develop a high flexibility to alter growth, development, and metabolism to adapt to the ever-changing environments. Multiple signaling pathways are involved in these processes and the molecular pathways to transduce various developmental signals are not linear but are interconnected by a complex network and even feedback mutually to achieve the final outcome. This review will focus on two important plant hormones, auxin and brassinosteroid (BR), based on the most recent progresses about these two hormone regulated plant growth and development in Arabidopsis, and highlight the cross-talks between these two phytohormones.

20.
Onco Targets Ther ; 9: 2675-82, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27226730

RESUMO

PURPOSE: Telomere shortening occurs in tumor tissues and peripheral blood lymphocytes of many common human malignancies, including lung cancer, but its variation in T-cells has never been investigated. Thus, the aim of this study was to assess telomere length in T-cells and its correlation with the clinical characteristics of patients with lung cancer. PATIENTS AND METHODS: A total of 40 patients with lung cancer but without prior cancer history and 25 healthy individuals were selected. T-cells were isolated and their telomere lengths were measured using quantitative real-time polymerase chain reaction methods. RESULTS: Telomere length in T-cells was significantly shorter in patients with lung cancer than in controls (P<0.001). Shorter telomere length was significantly associated with increased clinical stage (P=0.008) and distant metastasis (P=0.028). Naïve T-cells from patients with lung cancer had significantly decreased telomere length when compared with those from controls (P=0.012). CONCLUSION: The shortened telomere length in T-cells occurred in naïve T-cells and might be related to lung cancer progression.

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