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1.
Cell Death Dis ; 10(8): 583, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31378785

RESUMO

ULK1, the upper-most protein of the ULK1 complex, is emerging as a crucial node in autophagy induction. However, the regulation of ULK1 is not fully understood. In this study, we identified TOPK (T-LAK cell-originated protein kinase), an oncokinase, as a novel upstream kinase to phosphorylate ULK1. We found that TOPK could directly bind with and phosphorylate ULK1 at Ser469, Ser495, and Ser533. The phosphorylation of ULK1 at Ser469, Ser495, and Ser533 by TOPK decreased the activity and stability of ULK1. In addition, we want to examine the initiation of autophagy because the reduction activity of ULK1 reduces the occurrence of autophagy. We demonstrated that TOPK could inhibit the initiation and progression of autophagy in glioma cells. Furthermore, TOPK inhibition increased the sensitivity of glioma cells to temozolomide (TMZ). This discovery provides insight into the problem of TMZ-resistance in GBM treatment.

2.
J Cancer Res Clin Oncol ; 145(9): 2343-2355, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31280348

RESUMO

PURPOSE: Combinations of bortezomib (Velcade), cyclophosphamide and dexamethasone have shown significant efficacy and safety for patients of newly diagnosed multiple myeloma (NDMM). In this study, we compared the efficacy and safety of modified VCD regimens with novel changes in bortezomib dose and schedule for NDMM. METHODS: Eighty-five NDMM patients from multiple centers were randomly assigned to a high-dose (1.6 mg/m2) (group A) or a low-dose (1.3 mg/m2) (group B) bortezomib, administrated on days 1, 6, 11, and 16 subcutaneously in a 4-week cycle for nine cycles, combined with 40 mg dexamethasone on bortezomib days and cyclophosphamide 300 mg/m2 on days 1-3 intravenously. RESULTS: After four cycles, complete response (CR) or better in group A (43.6%) was higher than that in group B (12.8%) (P = 0.002). During induction, for patients with R-ISS stage III, the CR or better rate in group A was superior to that in group B (P = 0.01). Of patients < 65, the CR or better rate of group A was superior to that of group B (P = 0.004). Rapid onset of CR occurred in group A (P < 0.01). Meanwhile, rate of 3-4 diarrhea was higher in group A (P = 0.03), which caused higher rate of dose reduction for patients ≥ 65 (P = 0.041). No significant difference between the two groups in PFS and OS. CONCLUSIONS: The studied high-dose VCD as induction regimen had an improved CR rate, especially in patients < 65 or with R-ISS stage III, and is feasible for young and high-risk patients. Trial registration ClinicalTrials.gov: NCT02086942.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bortezomib/administração & dosagem , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bortezomib/efeitos adversos , Ciclofosfamida/efeitos adversos , Dexametasona/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Teniposídeo/administração & dosagem , Resultado do Tratamento
3.
Plant Biotechnol J ; 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31199554

RESUMO

Cotton is widely cultivated globally because it provides natural fibre for the textile industry and human use. To identify quantitative trait loci (QTLs)/genes associated with fibre quality and yield, a recombinant inbred line (RIL) population was developed in upland cotton. A consensus map covering the whole genome was constructed with three types of markers (8295 markers, 5197.17 centimorgans (cM)). Six fibre yield and quality traits were evaluated in 17 environments, and 983 QTLs were identified, 198 of which were stable and mainly distributed on chromosomes 4, 6, 7, 13, 21 and 25. Thirty-seven QTL clusters were identified, in which 92.8% of paired traits with significant medium or high positive correlations had the same QTL additive effect directions, and all of the paired traits with significant medium or high negative correlations had opposite additive effect directions. In total, 1297 genes were discovered in the QTL clusters, 414 of which were expressed in two RNA-Seq data sets. Many genes were discovered, 23 of which were promising candidates. Six important QTL clusters that included both fibre quality and yield traits were identified with opposite additive effect directions, and those on chromosome 13 (qClu-chr13-2) could increase fibre quality but reduce yield; this result was validated in a natural population using three markers. These data could provide information about the genetic basis of cotton fibre quality and yield and help cotton breeders to improve fibre quality and yield simultaneously.

4.
Viruses ; 11(5)2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31035728

RESUMO

Nucleoprotein (N) is a key element in rabies virus (RABV) replication. To further investigate the effect of N on RABV, we manipulated an infectious cDNA clone of the RABV HEP-Flury to rearrange the N gene from its wild-type position of 1 (N-P-M-G-L) to 2 (P-N-M-G-L), 3 (P-M-N-G-L), or 4 (P-M-G-N-L), using an approach that left the viral nucleotide sequence unaltered. Subsequently, viable viruses were recovered from each of the rearranged cDNA and examined for their gene expression levels, growth kinetics in cell culture, pathogenicity in suckling mice and protection in mice. The results showed that gene rearrangement decreased N mRNA transcription and vRNA replication. As a result, all viruses with rearranged genomes showed worse replication than that of rHEP-Flury in NA cells at a MOI of 0.01, but equivalent or slightly better replication levels at a MOI of 3. Consequently, the lethality in suckling mice infected with N4 was clearly attenuated compared with rHEP-Flury. However, the protection to mice was not enhanced. This study not only gives us insight into the understanding of the phenotype of RABV N gene rearrangement, but also helps with rabies vaccine candidate construction.

5.
Acta Anaesthesiol Scand ; 63(7): 847-852, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30982953

RESUMO

BACKGROUND: The intranasal route of dexmedetomidine (DEX) administration is becoming increasingly popular for providing adequate sedation during short examinations in infants and children. However, data on the 90% effective dose (ED90) of intranasal DEX are rare in children under 3 years old. METHODS: This is a double-blind trial using a biased coin design up-and-down sequential method (BCD-UDM). Fifty-three children aged under 3 years old requiring DEX for EEG were included in our study. The first patient received 2.5 µg kg-1 DEX, and the dose of DEX administered to the subsequent patient was determined by the response of the previous patient. The patient responses were recorded and analysed to calculate the ED90 by isotonic regression. The 95% confidence interval (CI) was estimated using a bootstrapping method. RESULTS: Fifty-three patients were included in our study, of which 45 patients were successfully sedated, and the 8 instances of failed sedation were rescued using sevoflurane inhalation, allowing the completion of the procedure. The 90% effective dose of DEX was calculated to be 3.28 µg kg-1 , and the 95% CI was 2.74 ~ 3.39 µg kg-1 . No significant adverse events occurred in any of the patients. CONCLUSION: The 90% effective dose of intranasal DEX sedation for EEG was 3.28 µg kg-1 in children under 3 years old.

6.
Cell Mol Immunol ; 2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30842630

RESUMO

Epigenetic modifications to histones dictate the differentiation of naïve CD4+ T cells into different subsets of effector T helper (TH) cells. The histone methyltransferase enhancer of zeste homolog 2 (EZH2) has been implicated in the mechanism regulating the differentiation of TH1, TH2 and regulatory T (Treg) cells. However, whether and how EZH2 regulates follicular helper T (TFH) cell differentiation remain unknown. Using a mouse model of acute lymphocytic choriomeningitis virus (LCMV) infection, we observed abundant EZH2 expression and associated H3K27me3 modifications preferentially in the early committed virus-specific TFH cells compared to those in TH1 cells. Ablation of EZH2 in LCMV-specific CD4+ T cells leads to a selective impairment of early TFH cell fate commitment, but not late TFH differentiation or memory TFH maintenance. Mechanistically, EZH2 specifically stabilizes the chromatin accessibility of a cluster of genes that are important for TFH fate commitment, particularly B cell lymphoma 6 (Bcl6), and thus directs TFH cell commitment. Therefore, we identified the chromatin-modifying enzyme EZH2 as a novel regulator of early TFH differentiation during acute viral infection.

7.
Front Immunol ; 10: 169, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30814995

RESUMO

The long-term persistence of viral antigens drives virus-specific CD8 T cell exhaustion during chronic viral infection. Yet exhausted, CD8 T cells are still endowed with certain levels of effector function, by which they can keep viral replication in check in chronic infection. However, the regulatory factors involved in regulating the effector function of exhausted CD8 T cell are largely unknown. Using mouse model of chronic LCMV infection, we found that the deletion of transcription factor TCF-1 in LCMV-specific exhausted CD8 T cells led to the profound reduction in cytokine production and degranulation. Conversely, ectopic expression of TCF-1 or using agonist to activate TCF-1 activities promotes the effector function of exhausted CD8 T cells. Mechanistically, TCF-1 fuels the functionalities of exhausted CD8 T cells by promoting the expression of an array of key effector function-associated transcription regulators, including Foxo1, Zeb2, Id3, and Eomes. These results collectively indicate that targeting TCF-1 mediated transcriptional pathway may represent a promising immunotherapy strategy against chronic viral infections by reinvigorating the effector function of exhausted virus-specific CD8 T cells.

8.
J Neurol ; 266(6): 1474-1480, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30911824

RESUMO

OBJECTIVE: Subclinical abnormalities, including microangiopathy, swelling of nerve fibers, visual field abnormalities and visual functional impairments had been reported in Leber's hereditary optic neuropathy (LHON) carriers. The purpose of this study was to investigate microstructural changes of brain white matter in asymptomatic LHON carriers using DTI and tract-based spatial statistics (TBSS). METHODS: DTI and neuro-ophthalmologic measurements were acquired in 14 LHON carriers and 15 gender- and age-matched healthy controls, and diffusion metrics, including fractional anisotropy (FA), axial (AD), radial diffusion (RD) and mean diffusion (MD) were calculated. Intergroup differences in diffusion metrics were compared regressing out potential nuisance covariates of age and gender. A correlation analysis was performed to test associations between abnormal neuro-ophthalmologic measures and diffusion metrics while controlling the effects of age and gender. RESULTS: Compared to healthy controls, LHON carriers showed a weak increase of thickness of the retinal nerve fiber layer (RNFL) of the right inferior quadrant (F = 5.22, p = 0.032, before multiple comparison correction). LHON carriers exhibited widespread decreased FA value (bilateral anterior thalamic radiations, bilateral corticospinal tracts, major and minor forceps, bilateral inferior fronto-occipital fasciculi and left superior longitudinal fasciculus), increased RD value (bilateral anterior thalamic radiations, bilateral corticospinal tracts, major and minor forceps, bilateral inferior fronto-occipital fasciculi, bilateral inferior longitudinal fasciculi, bilateral superior longitudinal fasciculi and bilateral uncinate fasciculi) and increased MD value (bilateral anterior thalamic radiations, bilateral corticospinal tracts, minor forceps, bilateral inferior fronto-occipital fasciculi, bilateral inferior longitudinal fasciculi, left superior longitudinal fasciculus and bilateral uncinate fasciculi). Moreover, these changed diffusion metrics were not correlated with age, gender, LHON mutations and retinal measures in LHON carriers. CONCLUSION: Our results show microstructural alterations in brain white matter in asymptomatic LHON carriers, indicating that LHON-related genetic mutations themselves might result in occult white matter alterations in the brain.

9.
Nan Fang Yi Ke Da Xue Xue Bao ; 38(11): 1294-1299, 2018 Nov 30.
Artigo em Chinês | MEDLINE | ID: mdl-30514675

RESUMO

OBJECTIVE: To investigate the effects of propofol combined with hypoxia on cognitive function of immature rats and the possible role of p38 pathway and tau protein in mediating such effects. METHODS: Ninety 7-day-old (P7) SD rats were randomized for daily intraperitoneal injection of propofol (50 mg/kg) or lipid emulsion (5.0 mL/kg) for 7 consecutive days. After each injection, the rats were placed in a warm box (38 ℃) with an oxygen concentration of 18% (hypoxia), 21% (normal air), or 50% (oxygen) until full recovery of the righting reflex. Another 90 P7 rats were similarly grouped and received intraperitoneal injections of p-p38 blocker (15 mg/kg) 30 min before the same treaments. The phosphorylated tau protein, total tau protein and p-p38 content in the hippocampus were detected using Western blotting. The spatial learning and memory abilities of the rats were evaluated with Morris water maze test. RESULTS: Compared with lipid emulsion, propofol injection resulted in significantly increased levels of p-p38, phosphorylated tau and total tau proteins in rats with subsequent hypoxic or normal air treatment (P < 0.05), but propofol with oxygen and injections of the blocker before propofol did not cause significant changes in the proteins. Without subsequent oxygenation, the rats receiving injections of propofol, with and without prior blocker injection, all showed significantly prolonged latency time and reduced platform-crossing times and third quadrant residence time compared with the corresponding lipid emulsion groups (P < 0.05). With oxygen treatment, the rats in propofoland blocker-treated groups showed no significant difference in the performance in Morris water maze test from the corresponding lipid emulsion group. The results of Morris water maze test differed significantly between blocker-propofol group and propofol groups irrespective of exposures to different oxygen levels (P < 0.05), but not between the lipid emulsion and blocker group pairs with exposures to different oxygen levels. CONCLUSIONS: Propofol combined with hypoxia can affect the expression of tau protein through p38 pathway to impair the cognitive function of immature rats, in which oxygen plays a protective role.

10.
Clin Cancer Res ; 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30397177

RESUMO

PURPOSE: Cancer stem-like cells (CSCs) contribute to bladder cancer (BCa) chemotherapy resistance and progression, but the associated mechanisms have not been elucidated. This study determined whether blocking an autocrine signaling loop in CSCs improves the therapeutic effects of cis-platinum on BCa. EXPERIMENTAL DESIGN: The expression of the epithelial marker OV6 and other markers in human BCa specimens was examined by immunohistochemistry. The CSC properties of magnetic-activated cell sorting (MACS)-isolated OV6+ and OV6- BCa cells were examined. Molecular mechanisms were assessed through RNA-Seq, cytokine antibody arrays, co-immunoprecipitation (co-IP), chromatin immunoprecipitation (ChIP), and other assays. An orthotopic BCa mouse model was established to evaluate the in vivo effects of a YAP inhibitor (verteporfin) and a PDGFR inhibitor (CP-673451) on the cis-platinum resistance of OV6+ CSCs in BCa. RESULTS: Up-regulated OV6 expression positively associated with disease progression and poor prognosis for BCa patients. Compared with OV6- cells, OV6+ BCa cells exhibited strong CSC characteristics, including self-renewal, tumor initiation in NOD/SCID mice and chemotherapy resistance. YAP, which maintains the stemness of OV6+ CSCs, triggered PDGFB transcription by recruiting TEAD1. Autocrine PDGF-BB signaling through its receptor PDGFR stabilized YAP and facilitated YAP nuclear translocation. Furthermore, blocking the YAP/TEAD1/PDGF-BB/PDGFR loop with verteporfin or CP-673451 inhibited the cis-platinum resistance of OV6+ BCa CSCs in an orthotopic BCa model. CONCLUSIONS: OV6 could be a helpful indicator of disease progression and prognosis for BCa patients, and targeting the autocrine YAP/TEAD1/PDGF-BB/PDGFR loop might serve as a remedy for cis-platinum resistance in patients with advanced BCa.

11.
Chin J Nat Med ; 16(10): 756-765, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30322609

RESUMO

Liver injury remains a significant global health problem and has a variety of causes, including oxidative stress (OS), inflammation, and apoptosis of liver cells. There is currently no curative therapy for this disorder. Sanwei Ganjiang Prescription (SWGJP), derived from traditional Chinese medicine (TCM), has shown its effectiveness in long-term liver damage therapy, although the underlying molecular mechanisms are still not fully understood. To explore the underlining mechanisms of action for SWGJP in liver injury from a holistic view, in the present study, a systems pharmacology approach was developed, which involved drug target identification and multilevel data integration analysis. Using a comprehensive systems approach, we identified 43 candidate compounds in SWGJP and 408 corresponding potential targets. We further deciphered the mechanisms of SWGJP in treating liver injury, including compound-target network analysis, target-function network analysis, and integrated pathways analysis. We deduced that SWGJP may protect hepatocytes through several functional modules involved in liver injury integrated-pathway, such as Nrf2-dependent anti-oxidative stress module. Notably, systems pharmacology provides an alternative way to investigate the complex action mode of TCM.

12.
J Chromatogr A ; 1573: 18-27, 2018 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-30243735

RESUMO

The quantification of preservatives in cosmetics has attracted great attentions for their controversial and widespread use. HPLC is a prevailing method for preservatives determination among various analytical methods. However, it takes long time to fully separate these compounds because of the complexity of cosmetic matrices. In this study, a fast and green HPLC-DAD strategy assisted with second-order multivariate calibration methods based on alternating trilinear decomposition (ATLD) and multivariate curve resolution-alternating least squares (MCR-ALS) was developed for the simultaneous determination of eight selected preservatives in complex facial mask samples. This appealing strategy proved to be a useful tool for eliminating unknown interferences in complex matrices without complete separation, which benefited from the "second-order advantages" and thus made the determination of the eight analytes in facial mask samples shorten to 8.2 min under a fast elution program. In particular, for the first time, we focused on the applicability of ATLD method for modeling of HPLC-DAD data with severe signal overlapping and slight time shifts. The spiked recovery values were in the range of 71.4-124.6%, and the RMSEP and REP values ranged from 0.07 to 2.4 µg mL-1 and 1.3-14.5%, respectively, indicating that the ATLD method could provide satisfactory prediction. The resolved spectral profiles and concentration values were compared with those obtained by the MCR-ALS method, an excellent tool for modeling of data deviating from trilinearity. Both qualitative and quantitative results from the two methods were consistent with each other, which evidenced the competence of ATLD method in handling HPLC-DAD data with severe signal overlapping and slight time shifts.


Assuntos
Técnicas de Química Analítica/métodos , Cromatografia Líquida de Alta Pressão , Cosméticos/química , Algoritmos , Calibragem , Análise dos Mínimos Quadrados , Análise Multivariada
13.
Appl Opt ; 57(24): 6971-6975, 2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30129586

RESUMO

In this work, we demonstrate the thermal regeneration of fiber Bragg gratings written in the hydrogenated standard communication optical fibers by two annealing processes. The first annealing process is done at an intermediate temperature (500°C, 700°C, and 900°C) for a specific period of time before cooling down to room temperature. The second annealing is at 1000°C in which the thermal regeneration is attained. The experimental results show that the regenerated gratings that are preannealed at 700°C have charted a reflectivity larger than 65%. They have higher thermal stability compared to that of the standard annealing process. Meanwhile the difference in temperature sensitivity is very small. The temperature sensitivities of regenerated gratings, which have undergone only two annealing processes, are 16.1 pm/°C and 15.8 pm/°C, respectively.

14.
J Sep Sci ; 41(16): 3232-3240, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30009500

RESUMO

In this work, high-performance liquid chromatography with diode array detection was applied for the simultaneous determination of andrographolide and dehydroandrographolide in Andrographis paniculata and its preparations. As a result of the incomplete baseline separation caused by complex backgrounds, the classical univariate calibration method failed to determine accurate contents of the analytes. On this occasion, chemometric second-order calibration based on the well-known alternating trilinear decomposition algorithm was then explored to serve as a post-experimental remedial tool to solve this problem. By using the intelligent "mathematical separation" of alternating trilinear decomposition, the peak areas of the analytes do not need to be directly measured and the predictive results become accurate. The contents of andrographolide and dehydroandrographolide were determined to be (7.95 ± 0.15) and (1.85 ± 0.02) µg/mL for Andrographis paniculata, (1.34 ± 0.01) and (5.53 ± 0.04) µg/mL for its preparations, which was in agreement with those obtained by a reference liquid chromatography with mass spectrometry method. This study showed the superiority of second-order calibration method over classical univariate calibration method for simultaneous determination of multi-analytes in complex samples. It also proved that second-order calibration may be a good choice for remedying incomplete baseline separation problem, with the accompanied reduction of experimental burden and toxic organic solvents as well as analysis time and cost.


Assuntos
Andrographis/química , Diterpenos/análise , Calibragem , Cromatografia Líquida de Alta Pressão , Conformação Molecular
15.
Environ Monit Assess ; 190(8): 457, 2018 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-29995278

RESUMO

Breastfeeding is a specific and important way for women to eliminate harmful substances accumulated in body. Hexachlorobenzene (HCB), ß-hexachlorocyclohexane (ß-HCH), and 2,2-bis(p-chlorophenyl)-1,1-dichloroethene (p,p'-DDE) are dominant organochlorine compounds(OCCs) and persistent organic pollutants (POPs) accumulated in human being. Although a 6-month breastfeeding was suggested by the World Health Organization (WHO), the excretion characteristics of OCCs in human milk during the first 6-month lactation remain controversial. The main purpose of this study was to continuously monitor the three dominant OCC concentrations and reveal their elimination characteristic in human milk within the first 6-month lactation. To do that, with one sample per month, during their first 6-month lactation, human milk samples were continuously collected from 40 mothers after their first birth. The result showed that the concentrations of the three OCCs in human milk during the lactation continuously decreased from 51.7 to 39.9 µg/kg milk lipids for HCB, from 136.5 to 84.8 µg/kg milk lipids for ß-HCH, and from 307.3 to 192 µg/kg milk lipids, respectively. The excretion kinetics of each compound in milk lipids fitted zero-order kinetics during the 6-month lactation. The excretion rate of the three OCCs was approximately 3% per month for HCB and 7% per month for the other two compounds during the lactation, with tdec 1/2 of 13 months for HCB, 7.5 months for ß-HCH, and 8 months for p,p'-DDE. The excretion rate of the target compounds depended on initial deposited levels, compound properties, and exposure or input source.


Assuntos
Poluentes Ambientais/metabolismo , Hidrocarbonetos Clorados/metabolismo , Leite Humano/metabolismo , Adulto , Aleitamento Materno , Diclorodifenil Dicloroetileno/metabolismo , Monitoramento Ambiental , Feminino , Hexaclorobenzeno/análise , Hexaclorobenzeno/metabolismo , Hexaclorocicloexano/metabolismo , Humanos , Hidrocarbonetos Clorados/análise , Cinética , Leite Humano/química , Período Pós-Parto
16.
Front Immunol ; 9: 1127, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29875775

RESUMO

Follicular helper CD4+ T (TFH) cells are critical for optimal B-cell-mediated humoral immunity by initiating, fueling, and sustaining germinal center reactions. The differentiation of TFH cells relies on multiple intrinsic and extrinsic factors; however, the details by which these factors are integrated to coordinate TFH differentiation are largely unknown. In this study, using a mouse model of acute lymphocytic choriomeningitis virus (LCMV) viral infection, we demonstrate that mTOR complex 2 (mTORC2) kinase integrates TCR signaling and ICOS-mediated co-stimulation to promote late differentiation and functional maturation of virus-specific TFH cells. Specifically, mTORC2 functions to maintain TFH lineage specifications, including phenotypes, migratory characteristics, and functional properties. Thus, our results highlight the importance of mTORC2 in guarding TFH phenotypic and functional maturation.

17.
Appl Opt ; 57(15): 4237-4244, 2018 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-29791400

RESUMO

An in-fiber Mach-Zehnder interferometer (MZI) is proposed and experimentally demonstrated for relative humidity (RH) and temperature measurements. The MZI is formed by a grapefruit-shaped photonic crystal fiber (G-PCF) cascaded with a short section of multimode fiber that serves as a mode coupler. To enhance sensitivity to humidity, femtosecond laser micromachining was performed to remove a portion of cladding of the G-PCF to expose its core to the ambient medium. The output interference spectrum is fast Fourier transformed to produce a spatial frequency spectrum that describes the intensity composition of the cladding modes in the MZI. In our investigation, it was observed that the interference dip intensity has a sensitivity of -0.077 dB/% RH to the change of RH in the range of 25%-80% RH, whereas the dip wavelength has a temperature sensitivity of ∼3.3 pm/°C in the range of 25°C-70°C. In addition, the dip intensity was insensitive to temperature. These characteristics have provided convenience in eliminating temperature cross talk and achieving accurate humidity measurement.

18.
Ann Hum Genet ; 82(5): 244-253, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29663307

RESUMO

Recent studies suggested that long noncoding RNAs (lncRNAs) were widely transcribed in the genome, but their potential roles in the genetic complexity of human disorders required further exploration. The purpose of the present study was to explore genetic polymorphisms of lncRNAs associated with bone mineral density (BMD) and its potential value. Based on the lncRNASNP database, 55,906 lncSNPs were selected to conduct a genome-wide association study meta-analysis among 11,140 individuals of seven independent studies for BMDs at femoral neck (FN), lumbar spine, and total hip (HIP). Promising results were replicated in Genetic Factors for Osteoporosis Consortium (GEFOS Sequencing, n = 32,965). We found two lncRNA loci that were significantly associated with BMD. MEF2C antisense RNA 1 (MEF2C-AS1) located at 5q14.3 was significantly associated with FN-BMD after Bonferroni correction, and the strongest association signal was detected at rs6894139 (P = 3.03 × 10-9 ). LOC100506136 rs6465531 located at 7q21.3 showed significant association with HIP-BMD (P = 7.43 × 10-7 ). MEF2C-AS1 rs6894139 was replicated in GEFOS Sequencing with P-value of 1.43 × 10-23 . Our results illustrated the important role of polymorphisms in lncRNAs in determining variations of BMD and provided justification and evidence for subsequent functional studies.

19.
Clin Cancer Res ; 24(18): 4612-4626, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-29691294

RESUMO

Purpose: Cancer stem-like cells (CSC) contribute to the progression and androgen deprivation therapy (ADT) resistance of prostate cancer. As CSCs depend on their specific niche, including tumor-associated macrophages (TAM), elucidating the network between CSCs and TAMs may help to effectively inhibit the progression and ADT resistance of prostate cancer.Experimental Design: The underlying intracellular mechanism that sustains the stem-like characteristics of CSCs in prostate cancer was assessed via RNA sequencing, co-immunoprecipitation, chromatin immunoprecipitation, and other assays. A coculture system and cytokine antibody arrays were used to examine the interaction network between CSCs and TAMs. In addition, an orthotopic prostate cancer model was established to evaluate the in vivo effects of the combined targeting of CSCs and their interaction with TAMs on ADT resistance.Results: Autophagy-related gene 7 (ATG7) facilitated the transcription of OCT4 via ß-catenin, which binds to the OCT4 promoter, promoting CSC characteristics in prostate cancer, including self-renewal, tumor initiation, and drug resistance. In addition, CSCs remodeled their specific niche by educating monocytes/macrophages toward TAMs, and the CSC-educated TAMs reciprocally promoted the stem-like properties of CSCs, progression and ADT resistance of prostate cancer via IL6/STAT3. Furthermore, the combined targeting of CSCs and their interaction with TAMs by inhibiting ATG7/OCT4 and IL6 receptor effectively ameliorated ADT resistance in an orthotopic prostate cancer model.Conclusions: Targeting CSCs and their niche may prove to be a more powerful strategy than targeting CSCs alone, providing a rational approach to ameliorating ADT resistance in prostate cancer. Clin Cancer Res; 24(18); 4612-26. ©2018 AACR.

20.
Arch Virol ; 163(7): 1889-1895, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29594364

RESUMO

Rabies, which is caused by the rabies virus (RABV), is an ancient zoonosis that has a high mortality rate. Previous studies have indicated that recombinant RABV expressing canine interleukin-6 (rHEP-CaIL6), induced more virus-neutralizing antibodies than parental RABV in mice following intramuscular immunization. To investigate the immune response induced in the CNS by rHEP-CaIL6 after intranasal or intracranial administration in mice, the permeability of the blood-brain barrier (BBB), the infiltration of CD3 T cells, and innate immune response-related effector molecules in the CNS were examined. It was observed that infection of rHEP-CaIL6 led to enhanced BBB permeability following intranasal infection. More CD3 T cells infiltrated into the central nervous system (CNS) in mice infected with rHEP-CaIL6 than in those infected with the HEP-Flury strain. Furthermore, rHEP-CaIL6 induced an increased expression of innate immune response-related effector molecules, compared with the parental HEP-Flury strain, within the CNS. Taken together, these findings suggest that rHEP-CaIL6 induced stronger immune responses in mice brains, which is more beneficial for virus clearance. These results may also partly illustrate the role of IL6 in RABV infection.


Assuntos
Encéfalo/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Vírus da Raiva/genética , Vírus da Raiva/imunologia , Raiva/imunologia , Administração Intranasal , Animais , Barreira Hematoencefálica , Encéfalo/virologia , Cães , Imunidade Inata , Fatores Imunológicos , Camundongos , Raiva/virologia , Linfócitos T/imunologia
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