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1.
J Transl Med ; 17(1): 357, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684954

RESUMO

BACKGROUND: The 18-gene tumor inflammation signature (TIS) is a clinical research assay that enriches for clinical benefit to immune checkpoint blockade. We evaluated its ability to predict clinical benefit of immunotherapy in cancer patients treated with PD-1 checkpoint inhibitors in routine clinical care. METHODS: The CERTIM cohort is a prospective cohort which includes patients receiving immune checkpoint inhibitors in Cochin University hospital. RNA extracted from 58 archival formalin fixed paraffin embedded tumor blocks (including 38 lung cancers, 5 melanomas, 10 renal carcinomas, 4 urothelial carcinomas and 1 colon carcinoma) was hybridized to a beta version of the NanoString® PanCancer IO360™ CodeSet using nCounter® technology. Gene expression signatures were correlated with tumor responses (by RECIST criteria) and overall survival. PD-L1 immunostaining on tumor cells was assessed in 37 non-small cell lung cancer (NSCLC) samples and tumor mutational burden (TMB) measured by whole exome sequencing in 19 of these. RESULTS: TIS scores were significantly associated with complete or partial response to anti-PD-1 treatment in the whole cohort (odds ratio = 2.64, 95% CI [1.4; 6.0], p = 0.008), as well as in the NSCLC population (odds ratio = 3.27, 95% CI [1.2; 11.6], p = 0.03). Patients whose tumor had a high TIS score (upper tertile) showed prolonged overall survival compared to patients whose tumor had lower TIS scores, both in the whole cohort (hazard ratio = 0.37, 95% CI [0.18, 0.76], p = 0.005) and in the NSCLC population (hazard ratio = 0.36, 95% CI [0.14, 0.90], p = 0.02). In the latter, the TIS score was independent from either PD-L1 staining on tumor cells (spearman coefficient 0.2) and TMB (spearman coefficient - 0.2). CONCLUSIONS: These results indicate that validated gene expression assay measuring the level of tumor microenvironment inflammation such as TIS, are accurate and independent predictive biomarkers and can be easily implemented in the clinical practice.

2.
Spectrochim Acta A Mol Biomol Spectrosc ; 226: 117649, 2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31629983

RESUMO

The protamine capped gold nanoclusters (AuNCs@PRT) were synthesized by an one-pot approach, and utilized as a nanoprobe for highly sensitive and selective assay of U(VI) ions. The method is based on the aggregation induced fluorescent quenching of AuNCs@PRT by U(VI) ions. Under optimum conditions, the decrease of fluorescence intensity displayed a good linear correlation with the concentration of U(VI) ions ranging from 20.4 nM to 9.74 µM, with a detection limit of 6.1 nM. The relative standard deviations were 3.86%, 1.41% and 1.71% via 11 detections at concentrations of 40 nM, 0.40 µM and 4.0 µM of U(VI), respectively. The quenching mechanism was demonstrated to be due to the binding of U(VI) towards PRT to cause the aggregation of AuNCs@PRT rather than metal-metal interaction. The results suggest the potential application of this approach for monitoring the level of U(VI) in environmental samples.

3.
Cancer Immunol Res ; 7(11): 1760-1774, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31624067

RESUMO

Head and neck squamous cell carcinomas (HNSCC) promote inflammation in the tumor microenvironment through aberrant NF-κB activation, but the genomic alterations and pathway networks that modulate NF-κB signaling have not been fully dissected. Here, we analyzed genome and transcriptome alterations of 279 HNSCC specimens from The Cancer Genome Atlas (TCGA) cohort and identified 61 genes involved in NF-κB and inflammatory pathways. The top 30 altered genes were distributed across 96% of HNSCC samples, and their expression was often correlated with genomic copy-number alterations (CNA). Ten of the amplified genes were associated with human papilloma virus (HPV) status. We sequenced 15 HPV- and 11 HPV+ human HNSCC cell lines, and three oral mucosa keratinocyte lines, and supervised clustering revealed that 28 of 61 genes exhibit altered expression patterns concordant with HNSCC tissues and distinct signatures related to their HPV status. RNAi screening using an NF-κB reporter line identified 16 genes that are induced by TNFα or Lymphotoxin-ß (LTß) and implicated in the classic and/or alternative NF-κB pathways. Knockdown of TNFR, LTBR, or selected downstream signaling components established cross-talk between the classic and alternative NF-κB pathways. TNFα and LTß induced differential gene expression involving the NF-κB, IFNγ, and STAT pathways, inflammatory cytokines, and metastasis-related genes. Improved survival was observed in HNSCC patients with elevated gene expression in T-cell activation, immune checkpoints, and IFNγ and STAT pathways. These gene signatures of NF-κB activation, which modulate inflammation and responses to the immune therapy, could serve as potential biomarkers in future clinical trials.

4.
Zhen Ci Yan Jiu ; 44(7): 516-9, 2019 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-31368284

RESUMO

OBJECTIVE: To observe the therapeutic effect of body acupuncture combined with auricular acupuncture in the treatment of woman menopause insomnia induced by disharmony between the heart and kidney. METHODS: A total of 111 outpatients with menopausal insomnia were randomly divided into treatment group (n=55, body acupoints plus auricular points) and control group (n=56, body acupoints). For control group, Shenmen (HT7), Sanyinjiao (SP6), Anmian, Zhaohai (KI6), Shenmai (BL62), Sishencong (EX-HN1), Xinshu (BL15) and Shenshu (BL21) were needled with filiform needles, and HT7, SP6, Anmian, BL15 and BL21 were also stimulated with electroacupuncture (EA) for 30 min, once every other day, 3 times a week for 3 weeks. For the treatment group, auricular points as Kidney, Shenmen, Sympathetic and Endocrine around the ear canal and the ear cavity were punctured with filiform needles in combination with the same intervention methods mentioned above in the control group. The quality and efficiency of sleep were assessed by using Pittsburgh Sleep Quality Index (PSQI) scale before and after the treatment. The symptom scores of traditional Chinese medicine (TCM) and the therapeutic effect were determined according to the "Guide Principles for Clinical Research of New Drugs of TCM" (formulated by Chinese Ministry of Health, 1997). RESULTS: After the treatment, the scores of sleep quantity and effective rate of PSQI scale, and those of insomnia and dreaminess, dysphoria with feverish sensation in chest, palms and soles, paplpitation and irritability, fatigue and forgetfulness of TCM were reduced significantly in both groups compared with their own pre-treatment (P<0.05). Of the 56 and 55 cases in the control and treatment groups, 18 (32.1%) and 30 (54.5%) experienced a marked improvement in their symptoms, 28 (50.0%) and 22 (40.0%) were effective, and 10 (17.9%) and 3 (5.5%) failed, with the effective rate being 82.1% and 94.5%, respectively. The therapeutic effect of stimulation of the body acupoints plus auricular acupoints was significantly superior to that of stimulation of simple body acupoints in lowering scores of PSQI scale, insomnia and dreaminess, dysphoria with feverish sensation in chest, palms and soles, dizziness and tinninus, paplpitation and irritability, and tital fever and night sweating of TCM, as well as the effective rate (P<0.05). CONCLUSION: Both body acupuncture and body acupuncture combined with auricular acupuncture are effective in the treatment of woman menopause insomnia due to disharmony between the heart and kidney, and the two combined treatment was evidently better.


Assuntos
Acupuntura Auricular , Distúrbios do Início e da Manutenção do Sono , Pontos de Acupuntura , Feminino , Coração , Humanos , Rim , Menopausa , Distúrbios do Início e da Manutenção do Sono/terapia , Resultado do Tratamento
5.
Food Funct ; 10(9): 5374-5385, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31393492

RESUMO

Many types of shellfish, including shrimp, are sometimes cooked before ingestion. Hence, it is necessary to investigate how cooking (boiling, pressure treatment or none (raw)) affects the structure, digestibility and immunoreactivity of multi-component shrimp muscle. Protein extraction, simulated gastrointestinal digestion, immunoreactivity, immunoglobulin E (IgE)-mediated human mast cell degranulation, morphology, particle size and UV absorbance scanning were used to investigate changes in the shrimp muscle upon treatment. The extractability of proteins and allergens was highest with 0.5 mol L-1 NaCl. Pressure treatment increased the digestibility and reduced the immunoreactivity of shrimp edible portions. Thermal processing induced the production of regular fiber bundles, blue shifts of absorbance peaks and reduction of particle size in the complex food matrix. These changes in macro- and micro-structure can further affect gastrointestinal digestibility and immunoreactivity due to the interactions between multiple components in the whole food. In conclusion, the digestibility, immunoreactivity and structure were altered by thermal processing of the complex food matrix.

6.
Chin J Dent Res ; 22(2): 93-104, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31172137

RESUMO

The repair of large bone defects remains a huge challenge for bone regenerative medicine. To meet this challenge, a number of bone substitutes have been developed over recent years to overcome the drawbacks of traditional autograft and allograft therapies. Thus, the improvement of the osteoinductive ability of these substitutes has become a major focus for research in the field of bone tissue engineering. It has been reported that some metallic ions play an important role in bone metabolism in the human body, and that bone repair could be enhanced by incorporating these ions into bone substitutes. Moreover, it is well documented that ions released from these substitutes such as magnesium, zinc, and strontium can increase the osteogenic and angiogenic properties of bone repair scaffolds. However, the mechanisms of action of these ions on cellular bioactivity are currently unclear. Therefore, in the present article, we highlight the recent use of bioactive ions in bone tissue engineering and discuss the effects of these ions on osteogenesis and neovascularisation.


Assuntos
Regeneração Óssea , Substitutos Ósseos , Humanos , Íons , Osteogênese , Engenharia Tecidual , Tecidos Suporte
7.
J Phys Chem B ; 123(29): 6364-6384, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31251618

RESUMO

The electrical double layer (EDL) at the amorphous silica-aqueous electrolyte interface is of long-standing scientific interest and current technological relevance. Using extensive molecular dynamics simulations, we have studied this EDL as a function of salt concentration for a silica surface charge density of -0.82e/nm2 (e = electron charge). The simulation results can be captured with a simple model by breaking the double-layer region into three zones: an inner region in which the Na+ counterion population is independent of [NaCl] and there are no Cl- co-ions, an intermediate region which hosts a population of nonexchangeable Na+ plus another group of Na+ and Cl- ions whose population is described by a Langmuir adsorption model, and an outer region where the ion distribution is well-described using the Poisson-Boltzmann theory. When the asymptotic [NaCl] >0.17 M, the adsorption of Na+ in the intermediate zone leads to an overcompensation of the negatively charged silica surface. Nonlinear spectroscopic experiments on the water-amorphous silica interface have been interpreted by others using the Gouy-Chapman model at low salt concentration and the constant capacitance model at high salt concentration. We discuss the applicability of these and other models and the implications for interpretation of the results of second harmonic and sum frequency generation experiments.

8.
Sci Rep ; 9(1): 5819, 2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30967575

RESUMO

We investigated the characteristics of the choriocapillaris flow voids using optical coherence tomography angiography (OCTA) in 85 patients (164 eyes) with hypertension (mean ± SD age, 56 ± 11 years; 45% women; 20% poorly controlled BP; 16% diabetes) who are without ocular diseases and determined possible correlations with systemic vascular risk factors. Data on 24-hour ambulatory blood pressure (BP), serum creatinine, and urine microalbumin/creatinine ratio (MCR) were collected. Estimated glomerular filtration rate (eGFR) was calculated based on CKD-EPI Creatinine Equation. OCTA imaging (6 × 6 mm scans; AngioVue) with quantitative microvascular analysis of the choriocapillaris was performed. Linear regression was used to investigate the association of systemic risk factors with area (percentage), size (pixels) and number of choriocapillaris flow voids. Diabetes (ß = 0.33; 95% CI, 0.02 to 0.63) and daytime systolic BP (ß = -0.13; 95% CI, -0.24 to -0.02) were associated with areas of flow voids. Age (ß = 0.21; 95% CI, 0.06 to 0.36) and daytime diastolic BP (ß = -0.18; 95% CI, -0.34 to -0.02) were associated with size of flow voids. Age (ß = -21.21; 95% CI, -31.79 to -10.63) and nighttime diastolic BP (ß = 13.89; 95% CI, 0.61 to 27.17) were associated with number of flow voids. Kidney parameters were not associated with any features of flow voids. In patients with hypertension, a higher BP appeared to increase blood flow in the choriocapillaris which needs to be considered when using the OCTA to study eye diseases in hypertensives.

9.
ACS Appl Mater Interfaces ; 11(17): 15322-15331, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30986029

RESUMO

Reactive oxygen species (ROS)-induced oxidative stress leads to neuron damage and is involved in the pathogenesis of chronic inflammation in neurodegenerative diseases (NDs), such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. Researchers, therefore, are looking for antiinflammatory drugs and gene therapy approaches to slow down or even prevent neurological disorders. Combining therapeutics has shown a synergistic effect in the treatment of human diseases. Many nanocarriers could be designed for the simultaneous codelivery of drugs with genes to fight diseases. However, only a few researches have been performed in NDs. In this study, we developed a mesoporous silica nanoparticle (MSN)-based approach for neurodegenerative therapy. This MSN-based platform involved multiple designs in the targeted codelivery of (1) curcumin, a natural antioxidant product, to protect ROS-induced cell damage and (2) plasmid RhoG-DsRed, which is associated with the formation of lamellipodia and filopodia for promoting neurite outgrowth. At the same time, TAT peptide was introduced to the plasmid RhoG-DsRed via electrostatic interaction to elevate the efficiency of nonendocytic pathways and the nuclear plasmid delivery of RhoG-DsRed in cells for enhanced gene expression. Besides, such a plasmid RhoG-DsRed/TAT complex could work as a noncovalent gatekeeper. The release of curcumin inside the channel of the MSN could be triggered when the complex was dissociated from the MSN surface. Taken together, this MSN-based platform combining genetic and pharmacological manipulations of an actin cytoskeleton as well as oxidative stress provides an attractive way for ND therapy.


Assuntos
Curcumina/farmacologia , Portadores de Fármacos/química , Nanopartículas/química , Crescimento Neuronal/efeitos dos fármacos , Plasmídeos/metabolismo , Dióxido de Silício/química , Citoesqueleto de Actina/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Curcumina/química , GTP Fosfo-Hidrolases/genética , Camundongos , Estresse Oxidativo , Tamanho da Partícula , Fragmentos de Peptídeos/química , Plasmídeos/química , Porosidade , Espécies Reativas de Oxigênio/metabolismo , Produtos do Gene tat do Vírus da Imunodeficiência Humana/química
10.
Environ Sci Pollut Res Int ; 26(10): 9672-9685, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30734252

RESUMO

Photocatalytic oxidation of formaldehyde (HCHO) is considered as one of the promising ways to resolve indoor air HCHO pollution. TiO2 has been well known as the most extended application in photocatalysis due to its strong oxidizing ability and stability. Owing to high activity under visible light irradiation, TiO2 and Bi2O3 doping mixed with Bi2WO6 was analyzed in this study. The formation of two kinds of heterojunction caused efficient charge separation, leading to the effective reduction in the recombination of photo-generated electron and hole. The special structure and enhanced performance of these catalysts were analyzed. For the first time, the loading of alkali salts was researched for photocatalytic oxidation. In order to understand the reaction mechanism of alkali salts enhanced effects, the catalysts were investigated by using BET, XRD, UV-Vis, FT-IR, SEM, and XPS. The results found more than 2 wt% of Na2SO4 loading and the mixed methods with different solutions were key factors affecting the performance of catalysts. Nearly 92% HCHO conversion could be completed over Bi2WO6/Bi0.15Ti0.85O2 (Na2SO4), and the concentration of HCHO was only 0.07 mg/m3 for 24 h, which was below the limit of specification in China. The results also indicated that the solution mixing method was more favorable to increase the HCHO conversion due to decrease the size of Bi0.15Ti0.85O2 particles. The catalysts with Na2SO4 loading provided more surface-adsorbed oxygen that facilitated the desorption of CO2 and markedly increased the photocatalytic oxidation of HCHO. Graphical abstract Plausible mechanism over W-Bi2WO6/ Bi0.15Ti0.85O2-Na2SO4 (1:4) catalysts.


Assuntos
Formaldeído/química , Modelos Químicos , Adsorção , Poluição do Ar em Ambientes Fechados/análise , Álcalis , Bismuto/química , Catálise , China , Luz , Oxirredução , Oxigênio , Processos Fotoquímicos , Espectroscopia de Infravermelho com Transformada de Fourier , Titânio/química , Compostos de Tungstênio/química
11.
Clin Cancer Res ; 25(9): 2860-2873, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30723145

RESUMO

PURPOSE: To identify deregulated and inhibitory miRNAs and generate novel mimics for replacement nanomedicine for head and neck squamous cell carcinomas (HNSCC). EXPERIMENTAL DESIGN: We integrated miRNA and mRNA expression, copy number variation, and DNA methylation results from The Cancer Genome Atlas (TCGA), with a functional genome-wide screen. RESULTS: We reveal that the miR-30 family is commonly repressed, and all 5 members sharing these seed sequence similarly inhibit HNSCC proliferation in vitro. We uncover a previously unrecognized inverse relationship with overexpression of a network of important predicted target mRNAs deregulated in HNSCC, that includes key molecules involved in proliferation (EGFR, MET, IGF1R, IRS1, E2F7), differentiation (WNT7B, FZD2), adhesion, and invasion (ITGA6, SERPINE1). Reexpression of the most differentially repressed family member, miR-30a-5p, suppressed this mRNA program, selected signaling proteins and pathways, and inhibited cell proliferation, migration, and invasion in vitro. Furthermore, a novel miR-30a-5p mimic formulated into a targeted nanomedicine significantly inhibited HNSCC xenograft tumor growth and target growth receptors EGFR and MET in vivo. Significantly decreased miR-30a/e family expression was related to DNA promoter hypermethylation and/or copy loss in TCGA data, and clinically with decreased disease-specific survival in a validation dataset. Strikingly, decreased miR-30e-5p distinguished oropharyngeal HNSCC with poor prognosis in TCGA (P = 0.002) and validation (P = 0.007) datasets, identifying a novel candidate biomarker and target for this HNSCC subset. CONCLUSIONS: We identify the miR-30 family as an important regulator of signal networks and tumor suppressor in a subset of HNSCC patients, which may benefit from miRNA replacement nanomedicine therapy.

12.
Mater Sci Eng C Mater Biol Appl ; 97: 793-802, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30678970

RESUMO

Photo-activated therapy is a non-invasive and promising medical technology for the treatment of cancers. Herein, we present Ce6-HA-CIS phototherapeutic nanohybrids composed of Cu-In-S (CIS) heterostructured nanorod (HS-rod), chlorin e6 (Ce6), and hyaluronic acid (HA) for the use in targeted photodynamic/photothermal therapy (PDT/PTT). In the Ce6-HA-CIS nanohybrids, the CIS HS-rod was investigated as a PTT agent to convert light into thermal energy, with Ce6 acting as a PDT agent to generate singlet oxygen (1O2). HA encapsulated the surface of the CIS HS-rod and aided the hydrophobic CIS HS-rod in achieving aqueous solubility. HA also acts as a tumor-specific targeting vector of cancer cells bearing the cluster determinant 44 receptor. Under light irradiation, the fabricated Ce6-HA-CIS nanohybrids exhibited high photothermal conversion efficiency, good photo-stability, and satisfactory photodynamic activity. In vitro and in vivo experiments demonstrated that Ce6-HA-CIS showed low cytotoxicity and synergistic photodynamic and photothermal cancer cell killing effects as compared to PTT or PDT agents alone. Therefore, these phototherapeutic nanohybrids may enhance cancer therapy in future clinical applications.


Assuntos
Nanotubos/química , Fármacos Fotossensibilizantes/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cobre/química , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Feminino , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Ácido Hialurônico/uso terapêutico , Índio/química , Luz , Masculino , Melanoma Experimental/tratamento farmacológico , Camundongos , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/química , Porfirinas/farmacologia , Porfirinas/uso terapêutico , Oxigênio Singlete/química , Oxigênio Singlete/metabolismo , Enxofre/química , Peixe-Zebra/crescimento & desenvolvimento , Peixe-Zebra/metabolismo
13.
ACS Appl Mater Interfaces ; 11(5): 4790-4798, 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30624037

RESUMO

Mesoporous silica nanoparticles (MSNs) hold great potential as a versatile platform for biomedical applications, especially drug delivery. However, evidence shows that MSNs even when PEGylated are rapidly cleared from the bloodstream by the monocyte phagocytic system. Erythrocytes, also called red blood cells (RBCs), can serve as biocompatible carriers of various bioactive substances, including drugs, enzymes, and peptides. In this work, we synthesize a series of fluorescent PEGylated MSNs with different synthetic diameters ranging from 10 to 200 nm and investigate the size effect on their encapsulation in human RBCs (hRBCs) by a hypotonic dialysis-based method. According to fluorescence images and flow cytometry analyses, we demonstrated that a hydrodynamic diameter below 30 nm is critical for efficient MSN encapsulation. Confocal microscopy and scanning electron microscopy images further confirmed that PEGylated MSNs were successfully embedded inside RBC. PEGylation serves an important role not only for stabilizing MSNs in biological milieu but also for reducing significant hemolysis caused by bare MSNs and thus for successful encapsulation. In addition to PEGylation, we further introduce positively charged functional groups onto the MSNs to show that nanoparticle-encapsulated hRBCs could serve as depots for delivering biological molecules through electrostatic attraction or chemical conjugation with MSNs. Also, we verify the existence of CD47 membrane protein, a marker of self, on the nanoparticle-encapsulated hRBCs and assess its ability of circulation in the blood, which could act as a circulation reservoir for delivering pharmacological substances through an osmosis-based method with MSNs.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Eritrócitos/metabolismo , Nanopartículas/química , Dióxido de Silício/química , Animais , Antígeno CD47/sangue , Antígeno CD47/metabolismo , Eritrócitos/química , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacocinética , Hemólise/efeitos dos fármacos , Humanos , Camundongos , Camundongos SCID , Microscopia Confocal , Nanopartículas/toxicidade , Polietilenoglicóis/química , Dióxido de Silício/farmacocinética
14.
Theriogenology ; 126: 75-80, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30537656

RESUMO

In vitro fertilization (IVF) and somatic cell nuclear transfer (SCNT) are important breeding techniques for livestock. High-quality MII oocytes produced from in vitro maturation (IVM) are required for the two techniques listed above. The ovaries used for IVM operations are primarily acquired from commercial abattoirs, and the pathogen status of slaughtered animals becomes an unavoidable issue. Our previous monitoring data showed that porcine circovirus type 2 (PCV-2) is the main pathogen present in ovaries from abattoirs. However, the characteristics and effects of PCV-2 infection in oocyte maturation and in vitro production (IVP) of embryos are unclear, and currently there are no relevant studies. Therefore, the aim of this study was to determine the PCV-2 infection pattern and determine whether it affects oocyte in vitro maturation and IVP embryo development. More than five hundred ovaries and five thousand oocytes were utilized in the present study. Polymerase chain reaction (PCR) was used to detect PCV-2 DNA in ovaries, follicular fluid (FF), oocytes, cumulus cells and IVP embryos. The effects of viral infections on the rate of oocyte maturation and IVP embryo development were evaluated. We also analyzed the number of copies of the virus in the IVM and IVP process by absolute quantitative fluorescence PCR. Our study showed that the prevalent virus subgenotype in ovaries was PCV-2a. PCV-2a infection did not significantly affect ovarian/oocyte morphology and maturation. Moreover, virus infection did not have a significant effect on the development of the IVP embryos except for a reduction in IVF blastocyst cell numbers. Further tests showed that the viral copy numbers fluctuated at different stages between the IVP embryos and culture medium. For the first time, this study identified the infection pattern of naturally sourced PCV-2 in the course of oocyte maturation and embryo development.


Assuntos
Infecções por Circoviridae/veterinária , Circovirus , Fertilização In Vitro/veterinária , Oócitos/virologia , Doenças dos Suínos/embriologia , Suínos/embriologia , Animais , Infecções por Circoviridae/embriologia , Meios de Cultura , DNA Viral/isolamento & purificação , Desenvolvimento Embrionário , Fertilização In Vitro/métodos , Técnicas de Maturação in Vitro de Oócitos/veterinária , Oócitos/crescimento & desenvolvimento , Suínos/virologia
15.
Environ Technol ; : 1-13, 2018 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-30379618

RESUMO

A series of MnOx-CeO2 catalysts with MOx doping (M = Cu, Fe, Co and La) supported on cordierite were synthesized by the citric acid complex method, showing preferable catalytic oxidation of chlorobenzene. The distribution of active oxides, surface areas, as well as the structural morphology of M-MnOx-CeO2 catalysts varied with the different Mn/Ce and M/Mn molar ratios. Meanwhile, physicochemical properties of these catalysts were characterized by XRD, BET, SEM, TEM, H2-TPR and IR. More importantly, the catalytic oxidation routes were also investigated where the process was from chlorobenzene to CO2, H2O, HCl and other by-products for the FeOx-MnOx-CeO2 and CuO-MnOx-CeO2 catalysts. The CuO-MnOx-CeO2 catalysts showed a higher chlorobenzene conversion, and the measured light-off temperature T90 was approximately 400°C. However, a large amount of chloropropane as main by-products was observed. For the FeOx-MnOx-CeO2 catalysts, more carbon monoxide could be found with inadequate oxidation. Comparative analyses of two catalysts indicated that the main cause of the oxidation activities and mechanisms were different in the oxidation capacity and water absorbability of FeOx and CuO. Nevertheless, all of these catalysts did not exhibit any deactivation due to chloride with a high reaction temperature, with chloride transformed to form HCl in the off-gas stream.

16.
Cell Rep ; 25(5): 1332-1345.e5, 2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-30380422

RESUMO

Cell lines are important tools for biological and preclinical investigation, and establishing their relationship to genomic alterations in tumors could accelerate functional and therapeutic discoveries. We conducted integrated analyses of genomic and transcriptomic profiles of 15 human papillomavirus (HPV)-negative and 11 HPV-positive head and neck squamous cell carcinoma (HNSCC) lines to compare with 279 tumors from The Cancer Genome Atlas (TCGA). We identified recurrent amplifications on chromosomes 3q22-29, 5p15, 11q13/22, and 8p11 that drive increased expression of more than 100 genes in cell lines and tumors. These alterations, together with loss or mutations of tumor suppressor genes, converge on important signaling pathways, recapitulating the genomic landscape of aggressive HNSCCs. Among these, concurrent 3q26.3 amplification and TP53 mutation in most HPV(-) cell lines reflect tumors with worse survival. Our findings elucidate and validate genomic alterations underpinning numerous discoveries made with HNSCC lines and provide valuable models for future studies.

17.
Brain Res ; 1700: 19-30, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30420052

RESUMO

The present study was undertaken because no previous developmental studies exist on MCH neurons in any avian species. After validating a commercially-available antibody for use in chickens, immunohistochemical examinations first detected MCH neurons around embryonic day (E) 8 in the posterior hypothalamus. This population increased thereafter, reaching a numerical maximum by E20. MCH-positive cell bodies were found only in the posterior hypothalamus at all ages examined, restricted to a region showing very little overlap with the locations of hypocretin/orexin (H/O) neurons. Chickens had fewer MCH than H/O neurons, and MCH neurons also first appeared later in development than H/O neurons (the opposite of what has been found in rodents). MCH neurons appeared to originate from territories within the hypothalamic periventricular organ that partially overlap with the source of diencephalic serotonergic neurons. Chicken MCH fibers developed exuberantly during the second half of embryonic development, and they became abundant in the same brain areas as in rodents, including the hypothalamus (by E12), locus coeruleus (by E12), dorsal raphe nucleus (by E20) and septum (by E20). These observations suggest that MCH cells may play different roles during development in chickens and rodents; but once they have developed, MCH neurons exhibit similar phenotypes in birds and rodents.

18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(5): 1437-1441, 2018 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-30295264

RESUMO

OBJECTIVE: To explore clinical features and laboratory data of glucose-6-phosphate dehydrogenase(G6PD)deficiency and to investigate the relationship between them. METHODS: Clinical data of 43 patients with G6PD deficiency was analyzed, the statistical method was applied to investigate the relationship between clinical features and laboratory data. RESULTS: Among 43 patients,neonatal jaundice occurred as the first symptom in 10 cases,while acute hemolytic anemia occurred as the first symptom in 23 cases. The major clinical symptoms of G6PD deficiency included icteric skin and/or sclera,dark urine,fever,gastrointestinal symptoms,fatigue and lethargy. Symptoms of 26 patients were caused by obvious inducement,including fava beans(61.5%),infection(34.6%)and miocardial infarction(3.8%). All of 43 patients showed decreased G6PD activity,while the level of their indirect serum bilirubin(IBIL)was positively correlated with reticulocyte percentage(Ret%,r=0.5881,P=0.013) and mean corpuscular volume(MCV,r=0.6854,P=0.0024). Patients with neonatal jaundice as the first symptom,showed higher level of Ret%(P<0.01)and MCV(P<0.001)and low RBC count(P<0.01)and low Hb level(P<0.01). as compard with patients with acute hemolytic anemia as first symptome. CONCLUSION: Neonatal jaundice and acute hemolytic anemia are common clinical features of G6PD deficiency. Laboratory results of IBIL,Ret% and MCV have auxiliary value to evaluate the severity of hemolysis induced by G6PD deficiency. Patients with neonatal jaundice as their first symptom show more severe hemolysis than those only suffered from acute hemolytic anemia.

19.
PLoS One ; 13(10): e0204829, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30273358

RESUMO

Naphthalene causes mouse airway epithelial injury. However, repeated exposures of naphthalene result in mouse airway tolerance. Previous results showed that toxicity or tolerance was correlated with changes of phosphorylcholine-containing lipids. In this study, a mass spectrometry-based lipidomic approach was applied to examine the effects of naphthalene-induced injury or tolerance in the male ICR mice. The injury model was vehicle x 7 plus 300 mg/kg naphthalene while the tolerant one was 200 mg/kg daily x 7 followed by 300 mg/kg naphthalene on day 8. The lung, liver, kidney, and serum samples were collected for profiles of phosphorylcholine-containing lipids including phosphatidylcholines (PCs) and sphingomyelins (SMs). A partial least-square-discriminate analysis model showed different lung phosphorylcholine-containing lipid profiles from the injured, tolerant, and control groups. Perturbation of diacyl-PCs and plasmenylcholines may be associated with enhanced membrane flexibility and anti-oxidative mechanisms in the lungs of tolerant mice. Additionally, alterations of lyso-PCs and SMs may be responsible for pulmonary dysfunction and inflammation in the lungs of injured mice. Moreover, serum PC(16:0/18:1) has potential to reflect naphthalene-induced airway injuries. Few phosphorylcholine-containing lipid alterations were found in the mouse livers and kidneys across different treatments. This study revealed the changes in lipid profiles associated with the perturbations caused by naphthalene tolerance and toxicity; examination of lipids in serum may assist biomarker development with the potential for application in the human population.

20.
Mikrochim Acta ; 185(10): 483, 2018 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-30269212

RESUMO

The authors report on a one-pot approach for synthesizing highly fluorescent protamine-stabilized gold nanoclusters. These are shown to be a viable nanoprobe for selective and sensitive fluorometric determination of lead(II) via quenching of fluorescence via Pb(II)-Au(I) interaction. Under optimized conditions, fluorescence measured at excitation/emission peaks of 300/599 nm drops in the 80 nM-15 µM lead(II) concentration range. The detection limit is 24 nM, and relative standard deviations (for n = 11) at concentrations of 0.10, 4.0 and 15 µM are 1.6, 2.5 and 1.9%, respectively. The relative recoveries of added lead(II) in the water samples ranged from 97.9 ± 2.29% to 101.2 ± 1.83%. Graphical abstract Lead(II) ions are found to be able to selectively and sensitively quench the fluorescence of the protamine-gold nanoclusters (PRT-AuNCs). Thereby, an inexpensive, selective and sensitive lead(II) assay was established.

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