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1.
J Acoust Soc Am ; 146(4): 2482, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31671957

RESUMO

Many underwater acoustic (UWA) channels exhibit impulsive noise, thereby severely degrading the performance of traditional channel estimation algorithms. This paper presents two channel estimation algorithms for impulsive noise, namely (i) the variable forgetting factor l1,0 recursive least sign algorithm (VFF-l1,0-RLSA) and (ii) the variable forgetting factor l2,0 recursive least sign algorithm (VFF-l2,0-RLSA), both of which exploit the group sparse multipath structure and maintain robustness under impulsive noise. By using the l1 norm of the estimation error as part of the cost function, RLSAs are better at detecting and rejecting impulsive noise than the recursive least squares algorithms. A mixed l1,0 or l2,0 norm is incorporated with a RLSA to achieve better performance in group sparse UWA channel estimation. The time-varying forgetting factor and regularization parameter in the two proposed algorithms help to improve their performance. Simulation results based on Arctic ice cracking noise demonstrate the robustness and superiority of the two proposed algorithms.

2.
Med Sci Monit ; 25: 8297-8305, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31682593

RESUMO

BACKGROUND Obesity has become a global public health problem. Obesity increases the risk of several lethal diseases. This study aimed to assess whether the obesity susceptibility was associated with genetic variation in vitamin D receptor (VDR) gene by conducting a meta-analysis. MATERIAL AND METHODS PubMed, EMBASE and Cochrane Library databases were screened for all relevant articles published up to October 2018. The pooled odds ratios (OR) were calculated using STATA 13.0 software for 4 polymorphisms in the VDR gene (ApaI, BsmI, FokI and TaqI). RESULTS Seven case-control studies, including 1188 obese patients and 1657 healthy controls, were recruited. The pooled findings showed that there were no associations between obesity risk and the VDR polymorphisms in ApaI, BsmI and TaqI loci overall. However, VDR TaqI polymorphism was associated with the risk of obesity in Asian under homozygous [TT versus tt: odds ratio (OR)=0.26, 95% confidence interval (CI)=0.14-0.49; P<0.001], heterozygous (Tt versus tt: OR=0.34, 95% CI=0.18-0.64; P=0.001), and dominant (TT+Tt versus tt: OR=0.30, 95% CI=0.17-0.52; P<0.001) models; FokI variant was related with increased risk of obesity only under dominant model (FF+Ff versus ff: OR=1.54, 95% CI=1.15-2.06; P=0.004). CONCLUSIONS Our meta-analysis results suggest that the T allele of TaqI may have a protective effect, while the F allele of FokI is proposed as a risk factor related to obesity.

3.
Acta Crystallogr C Struct Chem ; 75(Pt 11): 1494-1501, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31686660

RESUMO

A new potassium dysprosium polyborate, K3DyB6O12, has been prepared via the high-temperature molten salt method and structurally characterized by single-crystal X-ray diffraction analysis. The structure can be described as a three-dimensional framework composed of isolated bicyclic [B5O10]5- groups and Dy3+ and K+ ions. The Fourier transform IR (FT-IR) and ultraviolet-visible (UV-Vis) spectra were investigated. A series of K3Gd1-xDyxB6O12 phosphors was prepared and their photoluminescence properties were studied. The K3Gd1-xDyxB6O12 phosphors exhibit a strong yellow emission band at 577 nm (the 4F9/2→6H13/2 transition of Dy3+) under UV excitation of 275 nm (the 8S7/2→6IJ transition of Gd3+), suggesting the occurrence of the energy transfer Gd3+→Dy3+. The optimized doping concentration of the Dy3+ ion was 8 mol%. We may expect that K3Gd1-xDyxB6O12 is a promising pale-yellow emission phosphor for visual displays or solid-state lighting.

4.
Nat Commun ; 10(1): 5078, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699995

RESUMO

A multiprotein complex polarisome nucleates actin cables for polarized cell growth in budding yeast and filamentous fungi. However, the dynamic regulations of polarisome proteins in polymerizing actin under physiological and stress conditions remains unknown. We identify a previously functionally unknown polarisome member, actin-interacting-protein 5 (Aip5), which promotes actin assembly synergistically with formin Bni1. Aip5-C terminus is responsible for its activities by interacting with G-actin and Bni1. Through N-terminal intrinsically disordered region, Aip5 forms high-order oligomers and generate cytoplasmic condensates under the stresses conditions. The molecular dynamics and reversibility of Aip5 condensates are regulated by scaffolding protein Spa2 via liquid-liquid phase separation both in vitro and in vivo. In the absence of Spa2, Aip5 condensates hamper cell growth and actin cable structures under stress treatment. The present study reveals the mechanisms of actin assembly for polarity establishment and the adaptation in stress conditions to protect actin assembly by protein phase separation.

5.
Adv Mater ; : e1903448, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31682043

RESUMO

The emergence of cesium lead iodide (CsPbI3 ) perovskite solar cells (PSCs) has generated enormous interest in the photovoltaic research community. However, in general they exhibit low power conversion efficiencies (PCEs) because of the existence of defects. A new all-inorganic perovskite material, CsPbI3 :Br:InI3 , is prepared by defect engineering of CsPbI3 . This new perovskite retains the same bandgap as CsPbI3 , while the intrinsic defect concentration is largely suppressed. Moreover, it can be prepared in an extremely high humidity atmosphere and thus a glovebox is not required. By completely eliminating the labile and expensive components in traditional PSCs, the all-inorganic PSCs based on CsPbI3 :Br:InI3 and carbon electrode exhibit PCE and open-circuit voltage as high as 12.04% and 1.20 V, respectively. More importantly, they demonstrate excellent stability in air for more than two months, while those based on CsPbI3 can survive only a few days in air. The progress reported represents a major leap for all-inorganic PSCs and paves the way for their further exploration in order to achieve higher performance.

6.
Sci Adv ; 5(10): eaaw6870, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31681841

RESUMO

Erythrocytes or red blood cells (RBCs) represent a promising cell-mediated drug delivery platform due to their inherent biocompatibility. Here, we developed an antigen delivery system based on the nanoerythrosomes derived from RBCs, inspired by the splenic antigen-presenting cell targeting capacity of senescent RBCs. Tumor antigens were loaded onto the nanoerythrosomes by fusing tumor cell membrane-associated antigens with nanoerythrosomes. This tumor antigen-loaded nanoerythrosomes (nano-Ag@erythrosome) elicited antigen responses in vivo and, in combination with the anti-programmed death ligand 1 (PD-L1) blockade, inhibited the tumor growth in B16F10 and 4T1 tumor models. We also generated a tumor model showing that "personalized nano-Ag@erythrosomes" could be achieved by fusing RBCs and surgically removed tumors, which effectively reduced tumor recurrence and metastasis after surgery.

7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1353-1359, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607283

RESUMO

OBJECTIVE: To study the safety and effectiveness of humanized CD19-targeted CAR-T cells (hCART19s) for treatment of patients with refractory/relapsed (R/R) B-ALL. METHODS: The analyzed patients were 15 children and adults with relapsed/refractory B-ALL who not received treatment with murine CD19 CAR-T cells. The patients received a single dose (1×106/kg) of autologous hCART19 infusion after lymphodepletion chemotherapy based on cyclophosphamide and fludarabine. RESULTS: Among the 15 patients, 13/14 (92.9%) evaluable patients achieved complete remission (CR) or CR with incomplete recovery of blood cells (CRi) on day 30 after hCART19s infusion. At day 180 after the infusion, the overall survival rate was 73.3%, and the leukemia-free survival rate was 69.2%. The cumulative incidence of relapse was 24.5% and non-relapse mortality rate was 7.7%. During treatment,12/15 patients (80%) developed cytokine release syndrome (CRS) of grade 1-2, and 3 patients (20.0%) developed CRS of grade 3-5. Only one patient (6.7%) suffered from the reversible neurotoxicity. CONCLUSION: hCART19s can effectively treat refractory/relapsed (R/R) adult and children with B-ALL, and the incidence of treatment-related CRS and neurotoxicity is low.

8.
Nat Commun ; 10(1): 4855, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31649272

RESUMO

Noble metal nanomaterials have been widely used as catalysts. Common techniques for the synthesis of noble metal often result in crystalline nanostructures. The synthesis of amorphous noble metal nanostructures remains a substantial challenge. We present a general route for preparing dozens of different amorphous noble metal nanosheets with thickness less than 10 nm by directly annealing the mixture of metal acetylacetonate and alkali salts. Tuning atom arrangement of the noble metals enables to optimize their catalytic properties. Amorphous Ir nanosheets exhibit a superior performance for oxygen evolution reaction under acidic media, achieving 2.5-fold, 17.6-fold improvement in mass activity (at 1.53 V vs. reversible hydrogen electrode) over crystalline Ir nanosheets and commercial IrO2 catalyst, respectively. In situ X-ray absorption fine structure spectra indicate the valance state of Ir increased to less than + 4 during the oxygen evolution reaction process and recover to its initial state after the reaction.

10.
J Mol Cell Cardiol ; 137: 34-45, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31629736

RESUMO

Hypertensive cardiac remodeling is a major cause of heart failure. The immunoproteasome is an inducible form of the proteasome and its catalytic subunit ß5i (also named LMP7) is involved in angiotensin II-induced atrial fibrillation; however, its role in deoxycorticosterone-acetate (DOCA)-salt-induced cardiac remodeling remains unclear. C57BL/6 J wild-type (WT) and ß5i knockout (ß5i KO) mice were subjected to uninephrectomy (sham) and DOCA-salt treatment for three weeks. Cardiac function, fibrosis, and inflammation were evaluated by echocardiography and histological analysis. Protein and gene expression levels were analyzed by quantitative real-time PCR and immunoblotting. Our results showed that after 21 days of DOCA-salt treatment, ß5i expression and chymotrypsin-like activity were the most significantly increased factors in the heart compared with the sham control. Moreover, DOCA-salt-induced elevation of blood pressure, adverse cardiac function, chamber and myocyte hypertrophy, interstitial fibrosis, oxidative stress, and inflammation were markedly attenuated in ß5i KO mice. These findings were verified in ß5i inhibitor PR-957-treated mice. Moreover, blocking of PTEN (the gene of phosphate and tensin homolog deleted on chromosome ten) markedly attenuated the inhibitory effect of ß5i knockout on DOCA-salt-induced cardiac remodeling. Mechanistically, DOCA-salt stress upregulated the expression of ß5i, which promoted the degradation of PTEN and the activation of downstream signals (AKT/mTOR, TGF-ß1/Smad2/3, NOX, and NF-κB), which ultimately led to cardiac hypertrophic remodeling. This study provides new evidence of the critical role of ß5i in DOCA-salt-induced cardiac remodeling through the regulation of PTEN stability, and indicates that the inhibition of ß5i may be a promising therapeutic target for the treatment of hypertensive heart diseases.

11.
Orthop Surg ; 11(5): 850-856, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31663290

RESUMO

OBJECTIVE: To compare the superior-level facet joint violations (FJV) between robot-assisted (RA) percutaneous pedicle screw placement and conventional open fluoroscopic-guided (FG) pedicle screw placement in a prospective cohort study. METHODS: This was a prospective cohort study without randomization. One-hundred patients scheduled to undergo RA (n = 50) or FG (n = 50) transforaminal lumbar interbody fusion were included from February 2016 to May 2018. The grade of FJV, the distance between pedicle screws and the corresponding proximal facet joint, and intra-pedicle accuracy of the top screw were evaluated based on postoperative CT scan. Patient demographics, perioperative outcomes, and radiation exposure were recorded and compared. Perioperative outcomes include surgical time, intraoperative blood loss, postoperative length of stay, conversion, and revision surgeries. RESULTS: Of the 100 screws in the RA group, 4 violated the proximal facet joint, while 26 of 100 in the FG group had FJV (P = 0.000). In the RA group, 3 and 1 screws were classified as grade 1 and 2, respectively. Of the 26 FJV screws in the FG group, 17 screws were scored as grade 1, 6 screws were grade 2, and 3 screws were grade 3. Significantly more severe FJV were noted in the FG group than in the RA group (P = 0.000). There was a statistically significant difference between RA and FG for overall violation grade (0.05 vs 0.38, P = 0.000). The average distance of pedicle screws from facet joints in the RA group (4.16 ± 2.60 mm) was larger than that in the FG group (1.92 ± 1.55 mm; P = 0.000). For intra-pedicle accuracy, the rate of perfect screw position was greater in the RA group than in the FG group (85% vs 71%; P = 0.017). No statistically significant difference was found between the clinically acceptable screws between groups (P = 0.279). The radiation dose was higher in the FG group (30.3 ± 11.3 vs 65.3 ± 28.3 µSv; P = 0.000). The operative time in the RA group was significantly longer (184.7 ± 54.3 vs 117.8 ± 36.9 min; P = 0.000). CONCLUSIONS: Compared to the open FG technique, minimally invasive RA spine surgery was associated with fewer proximal facet joint violations, larger facet to screw distance, and higher intra-pedicle accuracy.

12.
Chem Biodivers ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31612620

RESUMO

One new p-terphenyl compound gliocladinins C and two disubstituted tetrahydrofuran derivatives chaetominin A and B were isolated from potato endophytic fungus  Chaetomium subaffine . The absolute configurations of these compounds were elucidated by HR-ESI-MS, NMR, the DP4+ probabilities and electronic circular dichroism (ECD) spectra. In addition gliocladinins C and chaetominin A showed cytotoxin activity against two selected human tumor cell lines (Hep-2 and HepG-2).

13.
Jpn J Clin Oncol ; 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31612912

RESUMO

OBJECTIVE: As an aggressive subtype of lung cancer, small-cell lung cancer (SCLC) presents a poor prognosis. Although molecular and clinical characteristics have been established for SCLC, limited investigation has been performed for predicting survival of SCLC patients. METHODS: Genomic alterations were profiled in Chinese SCLC patients (N = 37) using targeted sequencing. Clonal mutation burden (CMB) integrated the number of mutations with the clonal structure of the tumor. Specific pathways involving DNA damage repair (DDR) and cell cycle as well as CMB were studied as potential biomarkers for prognosis of SCLC. RESULTS: TP53 and RB1 gene mutations were the most common alterations (91.9% and 83.8%, respectively), followed by LRP1B, FAM135B, SPTA1, KMT2D, FAT1, and NOTCH3. Survival analysis revealed that mutation status of the DDR pathway was associated with worse OS in our cohort. Importantly, patients with higher CMB exhibited worse OS in our cohort and this observation was successfully validated in the cBioportal cohort. Moreover, multivariate analysis demonstrated CMB as a promising independent prognostic factor for OS in Chinese SCLC patients. Interestingly, patients with loss of function of RB1, validated by immunohistochemistry staining, appeared to have worse OS. CONCLUSIONS: The mutational profiling of Chinese SCLC patients signified an ethnicity dependent component. CMB was firstly found to be associated with OS of Chinese SCLC patients and could be regarded as a prognostic marker for SCLC.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31647966

RESUMO

BACKGROUND: Epidemiologic evidence suggests that exposure to particulate matter ≤2.5 µm (PM2.5) aggravates asthma. OBJECTIVE: Investigate the underlying mechanisms between PM2.5 exposure and asthma severity. METHODS: The relationship between PM2.5 exposure and asthma severity was investigated in an asthma model with CD4+ T cell-specific aryl hydrocarbon receptor (AhR) null mice. Effects of PM2.5 and polycyclic aromatic hydrocarbons (PAHs) on differentiation of T-helper 17/T-regulatory (Th17/Treg) cells were investigated by flow cytometry and quantitative reverse-transcription polymerase chain reaction. Mechanisms were investigated by mRNA sequencing, chromatin immunoprecipitation, bisulfite sequencing and glycolysis rates. RESULTS: PM2.5 impaired differentiation of Treg cells, promoted differentiation of Th17 cells, and aggravated asthma in an AhR-dependent manner. PM2.5 and one of its prominent PAHs, indeno[1,2,3-cd]pyrene (IP), promoted differentiation of Th17 cells by up-regulating hypoxia-inducible factor-1α expression and enhancing glycolysis via AhRs. Exposure to PM2.5 and IP enhanced glutamate oxaloacetate transaminase (Got)1 expression via AhRs and accumulation of R-2-hydroxyglutarate, which inhibited ten-eleven translocation methylcytosine dioxygenase-2 activity, resulting in hypermethylation in the forkhead box p3 locus and impaired differentiation of Treg cells. A Got1 inhibitor, (aminooxy)acetic acid, ameliorated asthma by shifting differentiation of Th17 cells to Treg cells. Similar regulatory effects of exposure to PM2.5 or IP on Th17/Treg imbalance were noted in human T cells and, in a case-control design, PAH exposure appeared to be a potential risk factor for asthma. CONCLUSIONS: The molecular pathways AhR-HIF-1α and AhR-Got1 mediate pulmonary responses upon exposure to PM2.5 through their ability to disturb the balance of Th17/Treg cells.

15.
Zhongguo Zhong Yao Za Zhi ; 44(15): 3358-3364, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602895

RESUMO

To evaluate the effect of Tripterygium Glycosides Tablets extract in the treatment of rheumatoid arthritis( RA). Clinical trials of treating rheumatoid arthritis with Tripterygium Glycosides Tablets published by Meta-analysis were retrieved from EMbase,PubMed,Clinical Trials,Web of Science,Cochrane Library,CNKI,Wanfang,VIP,CBM and Chi CTR,and comprehensively analyzed. A total of 3 studies were enrolled,the modified Sharp score( m TSS),tender join joint erosions( JE) and joint space narrowing( JSN) of Tripterygium Glycosides Tablets group were significant superior to those of control group,including positive drugs methotrexate( MTX) and salazopyridine( SSZ)( P<0. 01). Tripterygium Glycosides Tablets had an effect in treating RA. Due to the small sample size,this study shall be verified with high-quality,large-sample-size double-blinded RCTs.


Assuntos
Antirreumáticos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Glicosídeos/farmacologia , Tripterygium/química , Humanos , Comprimidos
16.
Curr Med Sci ; 39(5): 766-777, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31612395

RESUMO

The activation of hepatic stellate cells (HSCs) is a major event during hepatic fibrogenesis. Restoration of intracellular lipid droplet (LD) formation turns the activated HSC back to a quiescent state. Our previous studies have shown that curcumin suppresses HSC activation through increasing peroxisome proliferator-activated receptor, gamma (PPARγ) and 5' adenosine monophosphate-activated protein kinase (AMPK) activities. This study aims at evaluating the effect of curcumin on lipid accumulation in HSCs and hepatocytes, and further elucidating the underlying mechanisms. Now we showed that curcumin increased LD formation in activated HSCs and stimulated the expression of sterol regulatory element-binding protein and fatty acid synthase, and reduced the expression of adipose triglyceride lipase. Exogenous perilin5 expression in primary HSCs promoted LD formation. Perilipin 5 siRNA eliminated curcumin-induced LD formation in HSCs. These results suggest that curcumin recovers LD formation and lipid accumulation in activated HSCs by increasing perilipin 5 gene expression. Furthermore, inhibition of AMPK or PPARγ activity blocked curcumin's effect on Plin5 gene expression and LD formation. Our results provide a novel evidence in vitro for curcumin as a safe, effective candidate to treat liver fibrosis.

17.
J Ethnopharmacol ; 248: 112262, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31585162

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia ordosica Krasch. (AOK) has been used for rheumatic arthritis, cold headache, sore throat, etc. in traditional Chinese/Mongolian medicine and is used for nasosinusitis by local Mongolian "barefoot" doctors. Up to now, their mechanisms are still unclear. AIM: To evaluate the in vivo anti-inflammatory and allergic rhinitis (AR) alleviating effect as well as in vitro antimicrobial activities of AOK extracts to verify its ethno-medicinal claims. MATERIALS AND METHODS: Crude extracts (methanol/95%-ethanol/ethyl acetate) of AOK root/stem/leaf and fractions (petroleum ether/ethyl acetate/n-butanol/aqueous) of AOK root extract were prepared. Xylene-induced ear swelling model in mouse and ovalbumin (OVA)-induced AR model in guinea pig were established. Ear swelling degrees of mice were measured. The numbers of rubbing movement and sneezes of guinea pigs were counted to evaluate the symptoms of AR. The serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1 were measured by ELISA assay. The histological changes of nasal mucosa were investigated by light microscope after H&E staining. Antimicrobial activities of AOK extracts were also tested. LC-MS/MS analysis was performed to characterize the constituents of active extract and molecular docking was conducted to predict the biological mechanism. RESULTS: In ear-swelling model, extract (100.00 mg/kg) from the ethyl acetate layer of 95% ethanol (100.00 mg/kg) showed better swelling inhibition in mice than positive control (dexamethasone, 191.91 mg/kg). In AR model, extract from the ethyl acetate layer of 95% ethanol significantly alleviated the AR symptoms in guinea pigs, decreased the serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1, and reduced the infiltration of eosinophil in nasal mucosa. For Staphylococcus aureus, the ethyl acetate extract of AOK stem showed the highest inhibition (MIC=1.25 mg/mL), for Escherichia coli, n-butanol layer of 95% ethanol extract of AOK root showed the highest inhibition (MIC=15.00 mg/mL), for Candida glabrata, 95%-ethyl acetate extract of AOK leaf showed the best inhibition (MIC=0.064 mg/mL), while ethyl acetate and n-butanol layers showed similar inhibition on MRSA (MIC=7.50 mg/mL). LC-MS/MS characterization showed that dicaffeoylquinic acids account for more than 30% of ethyl acetate layer of AOK extract. Dicaffeoylquinic acids bind with histamine-1 receptor with high affinities and interesting modes. CONCLUSIONS: Extracts from AOK had interesting anti-inflammatory activity in mice, alleviating effect against OVA-induced AR in guinea pigs, and antimicrobial activities in vitro, which support the ethno-medicinal use of it. The main constituents in ethyl acetate layer of AOK root extract are dicaffeoylquinic acids and could bind with histamine-1 receptor well. These findings highlighted the importance of natural product chemistry study of AOK.

18.
Biomed Chromatogr ; : e4701, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31596954

RESUMO

Patrinia villosa (Thunb.) Juss. (PVJ) is described as pungent, bitter and slightly cold in Chinese medicine, and is associated with the large intestine, stomach and liver meridians. The preliminary experiments of our research team proved that PVJ total flavonoids have excellent inhibitory effects on liver cancer cells. And, the present experiment use the UPLC-Q-TOF-MS technology and serum pharmacochemistry methods to analyze the chemical components in vitro and in vivo of PVJ anti-liver tumors. The results show that a total of 14 chemical components are identified in the total flavonoids extract of PVJ, and it is mainly composed of flavonoids, flavonones, flavonols and phenolic acids. At the same time, 7 prototypical components and 7 metabolic components are detected in the drug-containing plasma. Hydrocaffeate and scutellarein are the phase I metabolites of caffeic acid and scutellarin, respectively. Sulfated apigenin, sulfated luteolin, sulfated kaempferol, and methylated kaempferol are the II phase metabolites of apigenin, luteolin, kaempferol, respectively. The experiment provides a reference for the research and development of anti-tumor drug candidates, and provides a basis for revealing the bioactive components of PVJ and anti-tumor mechanism.

19.
J Cell Physiol ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31603255

RESUMO

Glioblastoma multiforme (GBM) is a highly proliferative cancer with generally poor prognosis and accumulating evidence has highlighted the potential of long noncoding RNAs (lncRNAs) in the biological behaviors of glioma cells. This study focused on the identification of lncRNAs to identify targets for possible GBM prognosis. Microarray expression profiling found that 1,759 lncRNAs and 3,026 messenger RNAs (mRNAs) were upregulated, and 1932s lncRNA and 2,979 mRNAs were downregulated in GBM. Bioinformatics analysis and experimental verification identified TCONS_00020456 (TCON) for further analysis. In situ hybridization, along with immunohistochemical and receiver operating characteristic analysis determined TCON (truncation value = 3.5) as highly sensitive and specific in GBM. Grade IV patients with glioma life span with different lncRNA staining scores were analyzed. TCON staining scores below 3.5 indicated poor prognosis (life span ranging from 0.25 to 7 months), even if the glioma was surgically removed. TCON decreased significantly in GBM, and showed a coexpressional relationship with Smad2 and protein kinase C α (PKCα). Overexpression of TCON reduced the proliferation on one hand and migration, invasion on the other. TCON also inhibited epithelial-mesenchymal transformation and glioma progression in vivo, based on a nude mouse tumorigenicity assay. In addition, we predicted a potential binding site and intersection that microRNAs targeting Smad2, PKCα, and TCON through RACE pretest and bioinformatics analysis. Taken together, TCON, regarded as oncosuppressor, targeting the Smad2/PKCα axis plays a novel role in inhibiting the malignant progression of glioma. Moreover, it also demonstrates that the level of TCON can be used as a prognostic and diagnostic biomarker for GBM.

20.
J Exp Bot ; 2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31587070

RESUMO

An increased concentration of cytosolic Ca2+ is an early response of plant cells to heat shock (HS). Arabidopsis thaliana cyclic nucleotide-gated ion channel 6 (CNGC6) mediates heat-induced Ca2+ influx and is activated by cyclic adenosine monophosphate. However, it remains unclear how Ca2+ conductivity of the CNGC6 is negatively regulated under the elevated concentration of cytosolic Ca2+. In this study, A. thaliana CaM1/4, CaM2/3/5, CaM6 and CaM7 isoforms were found to bind to CNGC6 in varying degrees, and this binding was dependent on the presence of Ca2+ and IQ6, an atypical isoleucine glutamine motif in CNGC6. Knockout of CaM2, CaM3, CaM5 and CaM7 genes led to a marked increase in plasma membrane (PM) inward Ca2+ current under HS conditions; however, knockout of CaM1, CaM4 and CaM6 genes had no significant effect on PM Ca2+ current. Moreover, the deletion of the IQ6 from CNGC6 led to a marked increase in PM Ca2+ current under HS conditions. Taken together, the data presented here suggest that the CNGC6-mediated Ca2+ influx is likely to be negatively regulated by CaM2/3/5 and CaM7 isoforms under HS conditions, and the IQ6 plays important roles in CaM binding and the feedback regulation of the channel.

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