Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 815
Filtrar
1.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(1): 85-89, 2020 Jan 28.
Artigo em Chinês | MEDLINE | ID: mdl-32476378

RESUMO

OBJECTIVE: To observe the effects of resveratrol on body composition in adult catch-up growth rats and to explore the possible mechanism. METHODS: Eight-week-old male SD rats were randomly divided into 6 groups: normal controls for 4 weeks (NC4) group, caloric restriction for 4 weeks (R4) group, calorie restriction meanwhile resveratrol treatment for 4 weeks (R4E) group, normal controls for 12 weeks (NC12) group, catch-up growth (CUG) group and catch-up growth meanwhile resveratrol treatment for 8 weeks (CUGE) group. At the end of the four-week and twelve-week experimental period, the body weight, muscle and fat content of trunk and whole body, the ratio of trunk to whole body fat were detected, and at the end of twelve-week experimental period, the expression of SIRT1 in skeletal muscle and epididymal adipose tissue, and the expression of PPARγ in epididymal adipose tissue were detected. RESULTS: Compared with NC12 group, the fat content of trunk and whole body and trunk to whole body fat ratio in CUG group were increased significantly, along with the expression of PPARγ in epididymal adipose tissue was increased significantly (P<0.05), while the muscle content of trunk and whole body, the expression of SIRT1 in skeletal muscle and epididymal adipose tissue in CUG group were decreased significantly compared with NC12 group (P<0.05 or P<0.01); compared with CUG group, oral administration of resveratrol distinctly reduced the body fat content and trunk to whole body fat ratio in the CUGE groups, and the expression of PPARγ in epididymal adipose tissue of CUGE group was also significantly decreased (P<0.05). Meanwhile, the muscle content and the expression of SIRT1 in skeletal muscle and epididymal adipose tissue in CUGE group were significantly increased compared with the CUG group (P<0.05). CONCLUSION: Resveratrol can decrease body fat content, increase muscle content and improve abdominal fat accumulation in adult catch-up growth rats, and its mechanism may be associated with increasing SIRT1 expression in skeletal muscle and visceral adipose tissue, decreasing PPARγ expression in visceral adipose tissue.

2.
Blood Cancer J ; 10(5): 54, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393731

RESUMO

Seventy-six FDA-approved oncology drugs and emerging therapeutics were evaluated in 25 multiple myeloma (MM) and 15 non-Hodgkin's lymphoma cell lines and in 113 primary MM samples. Ex vivo drug sensitivities were mined for associations with clinical phenotype, cytogenetic, genetic mutation, and transcriptional profiles. In primary MM samples, proteasome inhibitors, dinaciclib, selinexor, venetoclax, auranofin, and histone deacetylating agents had the broadest cytotoxicity. Of interest, newly diagnosed patient samples were globally less sensitive especially to bromodomain inhibitors, inhibitors of receptor tyrosine kinases or non-receptor kinases, and DNA synthesis inhibitors. Clustering demonstrated six broad groupings of drug sensitivity linked with genomic biomarkers and clinical outcomes. For example, our findings mimic clinical observations of increased venetoclax responsiveness in t(11;14) patients but also identify an increased sensitivity profile in untreated patients, standard genetic risk, low plasma cell S-Phase, and in the absence of Gain(1q) and t(4;14). In contrast, increased ex vivo responsiveness to selinexor was associated with biomarkers of poor prognosis and later relapse patients. This "direct to drug" screening resource, paired with functional genomics, has the potential to successfully direct appropriate individualized therapeutic approaches in MM and to enrich clinical trials for likely responders.

3.
Phytochemistry ; 176: 112399, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32408190

RESUMO

Black aspergilli are distributed worldwide and represent one of the most prolific sources of metabolites with biomedical and agrochemical interests. However, due to their similar morphological characteristics and insufficient molecular identification, the taxonomic classification of black aspergilli remains ill-defined. The production of specialised metabolites is often unique for species among black aspergilli and could be used as diagnostic chemical markers for species identification. In this study, chemical investigation of Aspergillus tubingensis OUCMBIII 143291 led to the discovery of the diagnostic chemical marker asperazine, a complex diketopiperazine heterodimer, as well as two previously undescribed analogues, asperazine B and C. In addition, an undescribed 2-benzylpyridin-4(1H)-one-containing amide, pestalamide D, along with four known related metabolites were isolated. Their chemical structures, including their absolute configurations, were established on the basis of comprehensive spectral analysis and chiral HPLC analysis of the acidic hydrolysates. Asperazines B and C can serve as potential chemical markers for distinguishing A. tubingensis from A. niger, two representative species of black aspergilli that are usually incorrectly identified. Moreover, the isolated compounds were evaluated for their antifungal activity against eight phytopathogenic fungi including Alternaria alternata, A. brassicae, Botrytis cinerea, Colletotrichum lagenarium, Fusarium oxysporum, Gaeumannomyces graminis, Penicillium digitatum, and Valsa mali. Pestalamide D exhibited significant activities against B. cinerea, C. lagenarium, and V. mali, with MIC values of 4, 8, and 8 µg/mL, respectively, compared with the positive controls carbendazim (MICs = 8, 4, and 4 µg/mL) and prochloraz (MICs = 8, 8, and 4 µg/mL). The results of this study reveal two additional chemical markers and provide a powerful tool for the rapid identification of black aspergilli.

4.
Mol Med Rep ; 22(1): 317-327, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32377749

RESUMO

Facial jaw muscle is involved in the occurrence, development, treatment and maintenance of maxillofacial deformities. The structure and function of this tissue can be altered by changes in external stimuli, and orthodontists can regulate its reconstruction using orthopedic forces. The PI3K/Akt signaling pathway is most well­known for its biological functions in cell proliferation, survival and apoptosis. In the present study, the effects of the PI3K/Akt signaling pathway in cyclic stretch­induced myoblast apoptosis were investigated. For this purpose, L6 rat myoblasts were cultured under mechanical stimulation and treated with the PI3K kinase inhibitor, LY294002, to elucidate the role of the PI3K/Akt signaling pathway. Cells were stained with Hoechst 33258 to visualize morphological changes and apoptosis of myoblasts, and western blotting was performed to detect expression of Akt, phosphorylated (p)­Akt (Ser473), glycogen synthase kinase 3ß (GSK­3ß) and p­GSK­3ß (Ser9). After addition of PI3K inhibitor, the expression of total Akt and GSK­3ß did not significantly differ among groups; however, the levels of p­Akt and p­GSK­3ß were lower in inhibitor­treated groups than in those treated with loading stress alone. In addition, the rate of apoptosis in myoblasts subjected to cyclic stretch increased in a time­dependent manner, peaking at 24 h. Collectively, it was also demonstrated that the PI3K/Akt/GSK­3ß pathway plays an important role in stretch­induced myoblast apoptosis.

5.
J Int Med Res ; 48(5): 300060520913423, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32466699

RESUMO

OBJECTIVE: Previous studies reported the effect of dexmedetomidine on intrathecal anesthesia. In this review, we explored the impact of dexmedetomidine as an adjunct for lumbar anesthesia in patients undergoing cesarean section. METHODS: Two authors searched eligible random controlled trials in electronic databases, including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, the Chinese BioMedical database, Chinese Scientific Journal Database, and the Wanfang database. RESULTS: Ten trials comprising 970 patients were included in this review. Intrathecal dexmedetomidine significantly reduced the onset time of sensory block (standardized mean difference (SMD), -1.50, 95% confidence interval (CI) -2.15, -0.85, I2 = 92%) and motor block (SMD -0.77, 95% CI -1.50, -0.49, I2 = 60%) and prolonged the block duration time (sensory block: SMD 2.02, 95% CI 1.29, 2.74, I2 = 93%; motor block: SMD 1.90, 95% CI 1.07, 2.74, I2 = 94%). Patients who received dexmedetomidine showed a lower incidence of shivering. No significant difference was reported for the neonatal Apgar score and other complications. CONCLUSION: The use of intrathecal dexmedetomidine during cesarean section can shorten the onset time of spinal anesthesia and enhance the effect of local anesthetic. It has no significant impact on neonates and there were no other adverse events.

6.
Medicine (Baltimore) ; 99(20): e20326, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443384

RESUMO

The hypomethylation of the Cyclin D1 (CCND1) promoter induced by excess oxidative stress likely promotes the development of hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC). We aimed to evaluate methylation status of the CCND1 promoter as a new plasma marker for the detection of HBV-HCC.We consecutively recruited 191 participants, including 105 patients with HBV-HCC, 54 patients with chronic hepatitis B (CHB), and 32 healthy controls (HCs). Using methylation-specific polymerase chain reaction, we identified the methylation status of the CCND1 promoter in plasma samples. We analyzed the expression levels of the CCND1 mRNA in peripheral blood mononuclear cells by using quantitative real-time PCR. We assessed the plasma levels of superoxide dismutase, 8-hydroxydeoxyguanosine and malondialdehyde by using enzyme-linked immunosorbent assays.Patients with HBV-HCC (23.81%) presented a reduced methylation frequency compared with patients with CHB (64.81%) or HCs (78.13%) (P < .001). When receiver operating characteristic curves were plotted for patients with HBV-HCC versus CHB, the methylation status of the CCND1 promoter yielded diagnostic parameter values for the area under the curve of 0.705, sensitivity of 76.19%, and specificity of 64.81%, thus outperforming serum alpha-fetoprotein (AFP), which had an area under the curve of 0.531, sensitivity of 36.19%, and specificity of 90.74%. Methylation of the CCND1 promoter represents a prospective diagnostic marker for patients with AFP-negative HBV-HCC and AFP-positive CHB. The expression levels of CCND1 mRNA was increased in patients with HBV-HCC compared with patients with CHB (Z = -4.946, P < .001) and HCs (Z = -6.819, P < .001). Both the extent of oxidative injury and antioxidant capacity indicated by the superoxide dismutase, 8-hydroxydeoxyguanosine and malondialdehyde levels were increased in patients with HBV-HCC. Clinical follow up of patients with HBV-HCC revealed a worse overall survival (P = .012, log-rank test) and a decreased progression-free survival (HR = 0.109, 95%CI: 0.031-0.384) for the unmethylated CCND1 group than methylated CCND1 group.Our study confirms that oxidative stress appears to correlate with plasma levels of CCND1 promoter methylation, and the methylation status of the CCND1 promoter represents a prospective biomarker with better diagnostic performance than serum AFP levels.

7.
Int J Mol Sci ; 21(7)2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32252284

RESUMO

The symbiont endophytic fungi in tobacco are highly diverse and difficult to classify. Here, we sequenced the genomes of Curvularia trifolii and Leptosphaerulina chartarum isolated from tobacco plants. Finally, 41.68 Mb and 37.95 Mb nuclear genomes were sequenced for C. trifolii and L. chartarum with the scaffold N50, accounting for 638.94 Kb and 284.12 Kb, respectively. Meanwhile, we obtained 68,926 bp and 59,100 bp for their mitochondrial genomes. To more accurately classify C. trifolii and L. chartarum, we extracted seven nuclear genes and 12 mitochondrial genes from these two genomes and their closely related species. The genes were then used for calculation of evolutionary rates and for phylogenetic analysis. Results showed that it was difficult to achieve consistent results using a single gene due to their different evolutionary rates, while the phylogenetic trees obtained by combining datasets showed stable topologies. It is, therefore, more accurate to construct phylogenetic relationships for endophytic fungi based on multi-gene datasets. This study provides new insights into the distribution and characteristics of endophytic fungi in tobacco.

8.
Org Biomol Chem ; 18(17): 3258-3262, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32297885

RESUMO

Although the 2-position-selective decarboxylative coupling or addition of arylpropiolic acids with cyclic ethers has been intensively investigated, selective functionalization of arylpropiolic acids at the 3-position is still a big challenge. Herein, an intriguing and mild method for visible light induced regioselective addition of arylpropiolic acids by attacking exclusively at the 3-position with cyclic/acyclic ethers was developed. A variety of 3,3-bis-substituted acrylic acids were successfully obtained in moderate to excellent yields. A plausible reaction mechanism involving an energy transfer induced radical addition in the presence of visible light and photocatalyst was proposed.

9.
Nat Commun ; 11(1): 1624, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286257

RESUMO

A strategy that informs on countries' potential losses due to lack of climate action may facilitate global climate governance. Here, we quantify a distribution of mitigation effort whereby each country is economically better off than under current climate pledges. This effort-sharing optimizing approach applied to a 1.5 °C and 2 °C global warming threshold suggests self-preservation emissions trajectories to inform NDCs enhancement and long-term strategies. Results show that following the current emissions reduction efforts, the whole world would experience a washout of benefit, amounting to almost 126.68-616.12 trillion dollars until 2100 compared to 1.5 °C or well below 2 °C commensurate action. If countries are even unable to implement their current NDCs, the whole world would lose more benefit, almost 149.78-791.98 trillion dollars until 2100. On the contrary, all countries will be able to have a significant positive cumulative net income before 2100 if they follow the self-preservation strategy.

10.
Zootaxa ; 4728(2): zootaxa.4728.2.8, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-32230578

RESUMO

In the present paper, one new species and two new records of Erythroneurini from Guizhou Province, China are reported. The new species, Seriana bacilla sp. n. is described and illustrated. A key to distinguish all species of the genus is given. Another two species newly recorded from China, Empoascanara gracilis Dworakowska, 1992 and Tautoneura mayarami Mathew Ramakrishnan, 1996, are redescribed and illustrated.


Assuntos
Hemípteros , Animais , China
11.
Med Princ Pract ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32126568

RESUMO

OBJECTIVES: To observed the relationship between serum 25-hydroxyvitamin D (25-(OH) D) and different cognitive domains and evaluated the predictive value of 25-(OH) D level for cognitive impairment in patients with white matter lesions (WML). METHODS: The Mini-mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) were used to evaluate cognitive function in patients with WML. The differences in clinical data including 25-(OH) D were analysed between cognitive normality (n=87) and impairment (n=139) groups and variant cognitive domains analysed between groups of different levels of serum 25-(OH) D. And risk factors for cognitive impairments were evaluated with multivariate logistic regression analysis and receiver operating characteristic (ROC) curve of 25-(OH) D level were performed to examine the association between 25-(OH) D and WML with cognitive dysfunction. Results: As the severity of WML increased, the proportion of patients with low level of serum 25-(OH) D increased (P < 0.05) . The total MoCA scores and its all domain scores except for naming were significantly lower in patients with low levels of serum 25-(OH) D than that in patients with high levels of serum 25-(OH) D (P < 0.05). Multivariate logistic regression analyses showed that the serum 25-(OH) D levels, age, lower education level, hypertension, Systolic pressure, stroke, TC and uric acid levels were independently correlated with cognitive impairment. Conclusion:In patients with WML, low levels of serum 25-(OH) D is correlated with impairments of multiple cognitive domains and is an independent risk factor for cognitive impairment.

12.
Sci Total Environ ; 723: 137982, 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32222500

RESUMO

Through exploring price characteristics of carbon futures products in EU ET, this paper aims to provide China's policy makers with meaningful materials and references for understanding how a carbon trading market can be established and well regulated. Based on the dataset comprising of multiple sources including Euro stoxx600 index, coal and crude oil prices, natural gas prices and European clean energy company stock prices, etc., this paper uses BP neural network model to simulate the long-term trends of carbon futures prices in six scenarios that represent the typical features of a carbon trading market. The results show that: (1) the magnitude of economic development's effect on carbon price is the largest among other factors, with the shortest duration; (2) in comparison, the effect of black energy consumption is weaker, but its lasting duration is the longest; (3) the impact of clean energy development on carbon price is similar to that of black energy, but the effect magnitude and lasting duration are relatively smaller. These findings suggest three viable directions for the development of China's carbon trading market in future i.e. adjusting total quotas in accordance with economic development, establishing market price stabilization mechanism, and developing clean energy. The novelty of this paper is to simulate the long-term trend of carbon prices by constructing a carbon price prediction system.

13.
Environ Res ; 184: 109295, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32126376

RESUMO

BACKGROUND: Phthalate metabolites in follicular fluid (FF) may negatively affect normal folliculogenesis; however, the predictors of phthalate metabolite concentrations in urine and FF and relationships between urine and FF phthalate metabolite concentrations among women undergoing in vitro fertilization (IVF) are poorly understood. OBJECTIVE: To investigate predictors of phthalate metabolites in urine and FF and correlations between urine and FF phthalate metabolite concentrations among women undergoing IVF. METHOD: We recruited 305 women seeking infertility treatment at a reproductive center in Wuhan, China, from October to November 2016. Information regarding demographic characteristics, personal care product use and plastic material contact was obtained through direct interviews. Concentrations of 8 phthalate metabolites in urine and FF samples were measured using high-performance liquid chromatography and tandem mass spectrometry. Associations regarding metabolite concentrations in urine and FF samples were analysed by Spearman's correlation and linear regression. Generalized linear regression was used to examine potential predictors of phthalate metabolite concentrations in urine and FF. RESULTS: Weak to moderate associations between urine and FF samples were found for monoethyl phthalate (MEP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) (correlation coefficient: MEP, 0.350; MEOHP, 0.377); no associations were observed for other metabolites. The predictive powers of urinary metabolite concentrations in determining FF metabolite concentrations were uniformly low, with R2 ≤ 0.113. Body mass index (BMI) and educational level were inversely associated with the urinary concentrations of certain metabolites. Higher household income, intake of bottled drinks within 48 h, and use of shower gel and soap were frequently associated with higher urinary metabolite concentrations. BMI, higher household income and use of disposable plastic cups within 48 h were associated with higher metabolite concentrations in FF. CONCLUSION: Phthalate metabolite concentrations in urine and FF vary according to sociodemographic characteristics and lifestyle factors. Phthalate metabolite concentrations in urine may not be appropriate for estimating ovary phthalate exposure.

14.
Pathol Res Pract ; 216(5): 152914, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32147273

RESUMO

DNA methylation is one of the epigenetic mechanisms to regulate gene expression and frequently occurs in human cancer cells. T-cadherin (CDH13) is a new member of the cadherin superfamily and possesses multiple functions. Our study included 26 normal controls (NCs), 65 chronic hepatitis B patients (CHB), 14 liver cirrhosis patients (LC) and 157 hepatocellular carcinoma patients (HCC). We mainly focused on the mRNA expression and methylation status of CDH13 in peripheral blood mononuclear cells (PBMCs), which were detected by semi-quantitative real-time polymerase chain reaction (RT-qPCR) and methylation-specific polymerase chain reaction (MSP) respectively. The CDH13 mRNA level was lower in HCC, especially in early-stage of HCC than in NCs and CHB groups (p < 0.05). Methylation frequency of the CDH13 promoter was significantly higher in HCC patients than in the NCs and CHB groups (67.52 % vs 0.00 %, p < 0.001, 67.52 % vs 52.31 %, p < 0.05, respectively). CDH13 mRNA level was significantly and relatively lower in methylated groups than in unmethylated groups among the whole participants. The methylation level of CDH13 promoter in HCC might be influenced or partly influenced by some critical factors such as TBil, ALB and AFP (p < 0.05). As an important factor in signaling pathway regulating by CDH13 to promote carcinogenesis, JNK level was significantly higher in HCC which had a higher methylation frequency than in NCs, CHB and LC (p < 0.05). Furthermore, the combination of the methylated CDH13 level and AFP level showed a better score: AUC = 0.796 (SE = 0.031, 95 %CI 0.735-0.857; p < 0.001) in male and AUC = 0.832 (SE = 0.057, 95 %CI 0.721-0.944; p < 0.001) in female compared to AFP alone for diagnosing HCC from NCs, CHB and LC. The methylation of CDH13 promoter was an independent predictor for assessing the prognosis of HCC patients (r=-1.378 p < 0.05). In conclusion, hypermethylation of CDH13 in PBMCs was associated with the underexpression of mRNA and the high risk of HCC. The methylation status of the CDH13 promoter in PBMCs was a potential noninvasive biomarker to predict the prognosis of HCC patients.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32215933

RESUMO

The efficacy of dexmedetomidine in the prevention of postoperative delirium (POD) remains ambiguous, however, it has been used to reduce the incidence of delirium in elderly patients. Here, we conducted a meta-analysis study for assessing the effects of dexmedetomidine on POD among elderly patients following non-cardiac surgery. A systematic literature search was performed against the PubMed, EMBASE, Cochrane Library, and Web of Science databases, and all relevant literature published till November 30, 2019, were considered. Our analysis included 16 randomised controlled trials conducted with 4534 patients for exploring the effects of dexmedetomidine on POD in elderly patients following non-cardiac surgery. It was observed that the overall incidence of POD was significantly lower in the dexmedetomidine group than in the control group (risk ratio [RR] 0.51, 95% confidence interval [CI] 0.43-0.61, P < .01). Similar results were obtained from subgroup analysis upon comparison of the placebo (RR 0.52, 95% CI 0.41-0.66, P < .01, moderate quality of evidence), propofol-treated (RR 0.55, 95% CI 0.38-0.78, P < .01, low quality of evidence), and midazolam-treated (RR 0.38, 95% CI 0.20-0.71, P < .01, low quality of evidence) groups. Trial sequential analysis revealed that the cumulative z-value superseded the monitoring boundary and reached the required information size. However, patients who received dexmedetomidine had a higher incidence of bradycardia and hypotension. In conclusion, the meta-analysis revealed that dexmedetomidine appears to decrease the risk of POD in elderly patients following non-cardiac surgery. However, as some of the studies were heterogeneous and of low quality, high-quality trials are necessary for drawing more definitive conclusions.

16.
J Mol Cell Biol ; 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32219319

RESUMO

Error-free mitosis depends on accurate chromosome attachment to spindle microtubules, which is monitored by the spindle assembly checkpoint (SAC) signaling. As an upstream factor of SAC, the precise and dynamic kinetochore localization of Mps1 kinase is critical for initiating and silencing SAC signaling. However, the underlying molecular mechanism remains elusive. Here, we demonstrated that the multisite interactions between Mps1 and Ndc80 complex (Ndc80C) govern Mps1 kinetochore targeting. Importantly, we identified direct interaction between Mps1 tetratricopeptide repeat domain and Ndc80C. We further identified that Mps1 C-terminal fragment, which contains the protein kinase domain and C-tail, enhances Mps1 kinetochore localization. Mechanistically, Mps1 C-terminal fragment mediates its dimerization. Perturbation of C-tail attenuates the kinetochore targeting and activity of Mps1, leading to aberrant mitosis due to compromised SAC function. Taken together, our study highlights the importance of Mps1 dimerization and multisite interactions with Ndc80C in enabling responsive SAC signaling.

18.
Int J Phytoremediation ; : 1-10, 2020 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-32064907

RESUMO

A greenhouse pot experiment was conducted to assess the effects of biochar (BC) and arbuscular mycorrhizal fungus (AMF)-Funneliformis mosseae (Fm), Glomus versiforme (Gv) and Rhizophagus intraradices (Ri) on the plant growth and Cd/Pb accumulation by corn grown in the soils artificially contaminated with 5 mg Cd and 300 mg Pb kg-1 soil. The single AMF inoculation and combined usage of AMF and BC evidently improved the P contents of maize. Furthermore, the combined use of AMF and BC produced pronounced positive effect on corn growth, and the shoot biomass in Gv + BC group was 9.85-fold higher than that of the control. Meanwhile, the single BC addition and combined utilization of AMF and BC significantly reduced Cd and Pb concentrations in maize, and the greater reduces were found in the combined utilization, and the lowest Cd concentration of shoot was appeared in Gv + BC group. The single BC addition and combined application of AMF and BC significantly increased soil pH, and reduced soil diethylenetriaminepentaacetic acid (DTPA)-extractable Cd/Pb. This study demonstrated a synergistic effect between AMF (Gv, Fm, Ri) and BC on improving maize growth and decreasing Cd/Pb accumulation in maize, and the combined use of Gv and BC brought the most pronounced effect, which could provide a feasible strategy for safe production of maize from Cd/Pb-polluted soils.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32078016

RESUMO

Tumor-associated antigens (TAAs) have been tested in various clinical trials in cancer treatment but the patterns of specific T cell response to personalized TAA immunization remains to be fully understood. We report antigen-specific T cell responses in patients immunized with dendritic cell vaccines pulsed with personalized TAA panels. Tumor samples from patients were first analyzed to identify overexpressed TAAs. Autologous DCs were then transfected with pre-manufactured mRNAs encoding the full-length TAAs, overexpressed in the patients' tumors. Patients with glioblastoma multiforme (GBM) or advanced lung cancer received DC vaccines transfected with personalized TAA panels, in combination with low-dose cyclophosphamide, poly I:C, imiquimod and anti-PD-1 antibody. Antigen-specific T cell responses were measured. Safety and efficacy were evaluated. A total of ten patients were treated with DC vaccines transfected with personalized TAA panels containing 3-13 different TAAs. Among the seven patients tested for anti-TAA T cell responses, most of the TAAs induced antigen-specific CD4+ and/or CD8+ T cell responses, regardless of their expression levels in the tumor tissues. No Grade III/IV adverse events were observed among these patients. Furthermore, the treated patients were associated with favorable overall survival when compared to patients who received standard treatment in the same institution. Personalized TAA immunization-induced-specific CD4+ and CD8+ T cell responses without obvious autoimmune adverse events and was associated with favorable overall survival. These results support further studies on DC immunization with personalized TAA panels for combined immunotherapeutic regimens in solid tumor patients.Trial registration ClinicalTrials.gov, NCT02709616 (March, 2016), NCT02808364 (June 2016), NCT02808416 (June, 2016).

20.
Toxicology ; 432: 152392, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32014472

RESUMO

Acrylamide (AA) constitutes an important industrial chemical agent and well-known neurotoxin. However, the mechanism underlying AA-mediated neurotoxicity is extremely complicated and controversial. In this study, we found that activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome and its subsequent downstream inflammatory responses plays an important role in AA-induced neurotoxicity mechanisms. In vitro experiments revealed that AA (2.5 mM) induced BV2 microglial cytotoxicity and triggered NLRP3 inflammasome activation along with downstream proinflammatory cytokine interleukin-1ß and interleukin-18 expression. Treatment with inhibitor or NLRP3 siRNA efficiently protected BV2 microglial cells against AA-induced cytotoxicity and reversed NLRP3 inflammasome activation and its mediated inflammatory reaction. Similarly, AA exposure (50 mg/kg) for 10 consecutive days caused significant activation of NLRP3 inflammasomes and neuroinflammation in C57BL/6 mice, whereas inhibiting these effects through specific NLRP3 inflammasome blocker MCC950 (5 mg/kg) intervention or NLRP3 knock-out significantly ameliorated AA-induced ataxia, cerebellar Purkinje cells degeneration, and apoptosis. Furthermore, we demonstrated that antagonism of NLRP3 could also up-regulate the Nrf2 signalling pathway and related antioxidant genes. In conclusion, our findings indicate that activation of the NLRP3 inflammasome pathway is involved in AA-induced neurotoxicity, whereas MCC950 treatment or NLRP3 knock-out could effectively protect against AA-induced neurotoxic injury through the inhibition of neuroinflammation and activation of the Nrf2 antioxidant pathway. Therefore, the NLRP3 inflammasome might serve as a promising therapeutic target, with drugs designed to specifically inhibit this pathway potentially providing new avenues for preventing or ameliorating AA poisoning.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA