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1.
Aging (Albany NY) ; 12(1): 35-52, 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31926112

RESUMO

Hypoxia has been particularly associated with poor prognosis in cancer patients. Recent studies have suggested that hypoxia-related miRNAs play a critical role in various cancers, including colorectal cancer (CRC). In the present study, we found 52 differentially expressed miRNAs in HT-29 cells under hypoxic conditions versus normoxic conditions by analyzing the profiles of miRNAs. Using Cox model, we developed a hypoxia-related miRNA signature consisting of four miRNAs, which could successfully discriminate high-risk patients in the Cancer Genome Atlas (TCGA) training cohort (n=381). The prognostic value of this signature was further confirmed in the TCGA testing cohort (n=190) and an independent validation cohort composed of formalin-fixed paraffin-embedded clinical CRC samples (n=220), respectively. Multivariable Cox regression and stratified survival analysis revealed this signature was an independent prognostic factor for CRC patients. Time-dependent receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of this signature was significantly larger than that of any other clinical risk factors or single miRNA alone. A nomogram was constructed for clinical use, which incorporated both the miRNA signature and clinical risk factors and performed well in the calibration plots. Collectively, this novel hypoxia-related miRNA signature was an independent prognostic factor, and it possessed a stronger predictive power in identifying high-risk CRC patients than currently used clinicopathological features.

2.
Chemistry ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31957072

RESUMO

We firstly use diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (HEH) as a visible-light photoredox catalyst for cross coupling of arylhalides and arylsulfinates without transition-metal, sacrificial agent and mediator. This method is compatible with various functional groups and provides diaryl sulfones in good to high yields. Mechanistic studies indicate that this reaction undergoes the stepwise light irradiation of HE - , single electron transfer (SET) in donor-acceptor complex (DAC) from * HE - to arylhalide, trapping of aryl radical with sulfinate, SET oxidation of sulfone radical anion by HE • to sulfone via the DAC method.

3.
Life Sci ; 242: 117240, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31891722

RESUMO

Lycium barbarum polysaccharides (LBP) are derived from Wolfberry and have antioxidant activities. This study aimed to evaluate the efficacy of LBP for kidney injury in a rat model of sepsis. Male rats were divided randomly to control group (Con), LPS group (LPS), ulinastatin group (ULI), low dose LBP group (LBP-1), middle dose LBP group (LBP-2) and high dose LBP group (LBP-3). After intraperitoneal injection of LPS (5 mg/kg) to make sepsis model (LPS group), 10,000 U/kg ulinastatin were given in ULI group, and 200, 400 and 800 mg/kg LBP was given in LBP-1, -2, -3 group, respectively. Serum IL-1ß, IL-6, IL-8, TNF-α and NF-κB levels were measured by ELISA. Nrf2, Keap1, NF-κB, HO-1 and NQO1 expression levels were detected by PCR and Western blot analysis. We found that LBP decreased the levels of NF-κB and pro-inflammatory cytokines while attenuated kidney injury. In addition, LBP regulated Keap1-Nrf2/ARE signaling pathway in the kidney. In conclusion, LBP attenuates inflammation injury in the kidney via possible regulation of Keap1-Nrf2/ARE signaling.

4.
Theranostics ; 10(2): 498-515, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31903134

RESUMO

Rationale: STING is a critical player in the innate and adaptive immune system, sensing cytosolic DNA to activate the expression of interferon genes and regulate T lymphocytes, which drives immunogenic responses to cancer cells. Tumor-associated macrophages (TAMs), abundantly present in the tumor microenvironment, play a key role in cancer development. Gastric cancer is one of the most common and leading causes in cancer-related death worldwide. However, studies on the function and regulation of STING in TAMs and their roles in gastric cancer progression are still limited. Methods: We analyzed STING and CD68 expression of 200 pairs of gastric cancer and adjacent normal tissues by immunohistochemistry to identify the prognostic values of STING, as well as the correlations between STING and CD68 in gastric cancer. The characteristics of STING-altered macrophages, as well as their effects on cancer cell apoptosis and T cell differentiation were examined by flow cytometry. Cytokines secreted by STING-altered macrophages were identified by the Human Inflammation Array3 kit. Concentrations of soluble IL24 and IFN-ß were measured by ELISA. In vivo models, including spontaneous gastric cancer in p53+/- mice and cell line-based xenografts, were established, and clinical benefits of STING-altered macrophages were examined. Results: Our study identifies STING as a prognostic factor for gastric cancer, and for the first time demonstrated that knocking-down STING and STING activation by 2'3'-c-GAMP both promote TAMs polarizing into pro-inflammatory subtype and induce apoptosis of gastric cancer cells, mechanistically through IL6R-JAK-IL24 pathway. Conclusions : This study evaluated effects of targeting STING in TAMs in anti-gastric-cancer therapies. Moreover, we unveil a novel function of STING to activate the IL6R-JAK-IL24 pathway in macrophages.

5.
Fluids Barriers CNS ; 17(1): 2, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31906971

RESUMO

BACKGROUND: Genetic disruption of slc4a10, which encodes the sodium-dependent chloride/bicarbonate exchanger Ncbe, leads to a major decrease in Na+-dependent HCO3- import into choroid plexus epithelial cells in mice and to a marked reduction in brain intraventricular fluid volume. This suggests that Ncbe functionally is a key element in vectorial Na+ transport and thereby for cerebrospinal fluid secretion in the choroid plexus. However, slc4a10 disruption results in severe changes in expression of Na+,K+-ATPase complexes and other major transport proteins, indicating that profound cellular changes accompany the genetic manipulation. METHODS: A tandem mass tag labeling strategy was chosen for quantitative mass spectrometry. Alterations in the broader patterns of protein expression in the choroid plexus in response to genetic disruption of Ncbe was validated by semi-quantitative immunoblotting, immunohistochemistry and morphometry. RESULTS: The abundance of 601 proteins were found significantly altered in the choroid plexus from Ncbe ko mice relative to Ncbe wt. In addition to a variety of transport proteins, particularly large changes in the abundance of proteins involved in cellular energy metabolism were detected in the Ncbe ko mice. In general, the abundance of rate limiting glycolytic enzymes and several mitochondrial enzymes were reduced following slc4a10 disruption. Surprisingly, this was accompanied by increased ATP levels in choroid plexus cells, indicating that the reduction in capacity for energy metabolism was adaptive to high ATP rather than causal for a decreased capacity for ion and water transport. Ncbe-deficient cells also had a reduced cell area and decreased K+ content. CONCLUSION: Our findings suggest that the lack of effective Na+-entry into the epithelial cells of the choroid plexus leads to a profound change in the cellular phenotype, shifting from a high-rate secretory function towards a more dormant state; similar to what is observed during ageing or Alzheimer's disease.

6.
Sci Transl Med ; 12(525)2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915305

RESUMO

T cell activation is initiated upon binding of the T cell receptor (TCR)/CD3 complex to peptide-major histocompatibility complexes ("signal 1"); activation is enhanced by engagement of a second "costimulatory" receptor, such as the CD28 receptor on T cells binding to its cognate ligand(s) on the target cell ("signal 2"). CD3-based bispecific antibodies act by replacing conventional signal 1, linking T cells to tumor cells by binding a tumor-specific antigen (TSA) with one arm of the bispecific and bridging to TCR/CD3 with the other. Although some of these so-called TSAxCD3 bispecifics have demonstrated promising antitumor efficacy in patients with cancer, their activity remains to be optimized. Here, we introduce a class of bispecific antibodies that mimic signal 2 by bridging TSA to the costimulatory CD28 receptor on T cells. We term these TSAxCD28 bispecifics and describe two such bispecific antibodies: one specific for ovarian and the other for prostate cancer antigens. Unlike CD28 superagonists, which broadly activate T cells and resulted in profound toxicity in early clinical trials, these TSAxCD28 bispecifics show limited activity and no toxicity when used alone in genetically humanized immunocompetent mouse models or in primates. However, when combined with TSAxCD3 bispecifics, they enhance the artificial synapse between a T cell and its target cell, potentiate T cell activation, and markedly improve antitumor activity of CD3 bispecifics in a variety of xenogeneic and syngeneic tumor models. Combining this class of CD28-costimulatory bispecific antibodies with the emerging class of TSAxCD3 bispecifics may provide well-tolerated, off-the-shelf antibody therapies with robust antitumor efficacy.

7.
JCI Insight ; 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31935197

RESUMO

BACKGROUND: Siponimod (BAF312) is a selective sphingosine 1-phosphate receptor 1 and 5 (S1PR1, S1PR5) modulator recently approved for active secondary progressive multiple sclerosis (SPMS). The immunomodulatory effects of siponimod in SPMS have not been previously described. METHODS: We conducted a multi-centered randomized, double-blind, placebo-controlled AMS04 mechanistic study with 36 SPMS participants enrolled in the EXPAND trial. Gene expression profiles were analyzed using RNA derived from whole blood with Affymetrix Human Gene ST 2.1 microarray technology. We performed flow cytometry based assays to analyze the immune cell composition and microarray gene expression analysis on peripheral blood from siponimod-treated participants with SPMS relative to baseline and placebo during the first year randomization phase. RESULTS: Microarray analysis showed that immune-associated genes involved in T and B cell activation and receptor signaling were largely decreased by siponimod, which is consistent with the reduction of CD4+ T cells, CD8+ T cells, and B cells. Analysis done by flow cytometry showed that within the remaining lymphocyte subsets, there was a reduction in the frequencies of CD4 and CD8 naïve T cells and central memory cells, while T effector memory cells, anti-inflammatory Th2, and T regulatory (Treg) cells were enriched. Transitional Bregs (CD24hiCD38hi) and B1 cell subsets (CD43+CD27+) were enriched, shifting the balance in favor of regulatory B cells over memory B cells. The pro-regulatory shift driven by siponimod treatment included a higher proliferative potential of Tregs compared with non-Tregs, and upregulated expression of PD-1 on Tregs. Additionally, a positive correlation was found between regulatory T cells and regulatory B cells in siponimod treated participants. CONCLUSION: The shift toward an anti-inflammatory and suppressive homeostatic immune system may contribute to the clinical efficacy of siponimod in SPMS. TRIAL REGISTRATION: NCT02330965.

8.
Chemosphere ; 242: 125196, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31896208

RESUMO

Lanzhou, an ex-heavily polluted city, was awarded "The Award for Today's Transformative Step" in 2015 World Climate Conference at Paris for its great efforts on air quality improvement since 2012. However, the health benefits from this improvement remain unclear. Therefore, we collected time-series data covering deaths, weather variables and air pollutants during the two periods (2004-2009, 2014-2017) and fitted single-pollutant models using the generalized additive models to evaluate the change of mortality risks associated with air pollutants in Lanzhou. Results showed that the annual average concentrations of respirable particulate matter (PM10) and sulfur dioxide (SO2) dropped by 19.28% and 66.29%, while the nitrogen dioxide (NO2) increased by 16.61% in 2014-2017 compared to 2004-2009. During the period 2004-2009, we found a 10-µg/m3 increase in PM10 (lag 2), SO2 (lag 0-5) and NO2 (lag 0-5) were associated with mortality increments of 0.12% (95% CI: 0.01, 0.22), 0.86% (95% CI: 0.42, 1.31) and 1.29% (95% CI: 0.70, 1.90), respectively. During the period 2014-2017, the association between PM10 and daily deaths was not significant, but we observed a 10-µg/m3 increase in SO2 (lag 0-5) and NO2 (lag 4) were related to mortality increments of 4.23% (95% CI: 1.82, 6.70) and 0.85% (95% CI: 0.19, 1.52), respectively. From 2004-2009 to 2014-2017, we observed markedly decline of mortality risk due to PM10, but not SO2 or NO2. In conclusion, the mortality risk of PM10 in Lanzhou has declined obviously after the substantially improved air quality due to the enforcement of air pollution controlling policies.

9.
Brain Res Bull ; 156: 58-66, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31927062

RESUMO

Growing evidence suggests a critical role of astrocytes for pain regulation. The water channel protein aquaporin 4 (AQP4), a functional regulator of astrocytes, is involved in various neurological disorders. However, the pathophysiological roles of AQP4 in pain conditions remain unclear. In the present study, we investigated the effect of AQP4 gene knockout in central sensitization induced by complete Freund's adjuvant (CFA). The behavioral analysis revealed that mechanical allodynia and thermal hyperalgesia were more severe in AQP4 null mice than those of wild-type controls over the course of 11 days following CFA intraplantar injection. CFA caused activation of astrocytes with upregulated expression levels of AQP4 and glutamate transporter 1 (GLT1) in the dorsal horn of the spinal cord. AQP4 deficiency reduced GLT1 up-regulation, causing persistent expression of the neuronal activation marker Fos within superficial dorsal horn neurons, including glutamatergic neurons. However, AQP4 deletion did not affect CFA-evoked proinflammatory cytokine expression in the spinal cord. Together, these results have shown that AQP4 absence intensifies CFA-induced spinal central sensitization, which is associated with reduced compensatory up-regulation of GLT1, subsequently increasing glutamatergic overexcitation. Therefore, targeting spinal cord AQP4 may serve as a potential strategy for treatment of peripheral inflammation-evoked hyperalgesia.

10.
Cancer Lett ; 473: 74-89, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31904482

RESUMO

Gastrointestinal cancer causes countless deaths every year due to therapeutic resistance. However, whether metabolic alterations contribute to chemoresistance is not well understood. In this study, we report that fatty acid (FA) catabolism was activated in gastrointestinal cancer cells treated with oxaliplatin, which exhibited higher expression of the rate-limiting enzymes carnitine palmitoyltransferase 1B (CPT1B) and CPT2. The clinical analysis also showed that high expression of these enzymes was associated with poor oxaliplatin-based chemotherapy outcomes in patients. Furthermore, genetic or pharmacological inhibition of CPT2 with perhexiline disturbed NADPH and redox homeostasis and increased reactive oxygen species (ROS) generation and cell apoptosis in gastrointestinal cancer cells following oxaliplatin treatment. Specifically, the combination of oxaliplatin and perhexiline significantly suppressed the progression of gastrointestinal cancer in cell-based xenograft and patient-derived xenograft (PDX) models. Mechanistically, CPT2 was transcriptionally upregulated by nuclear factor of activated T cells 3 (NFATc3), which translocated to the nucleus in response to oxaliplatin treatment. In summary, our study suggests that the inhibition of CPT-mediated FA catabolism combined with conventional chemotherapy is a promising therapeutic strategy for patients with gastrointestinal cancers.

11.
J Am Chem Soc ; 142(2): 1057-1064, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31846307

RESUMO

Bis-labeling with a luminescent energy donor/acceptor pair onto biological substrates affords probes which give FRET readouts for the detection of interaction partners. However, the covalently bound luminophores bring about steric hindrance and nonspecific interaction, which probably perturb the biological recognition. Herein, we designed a highly sensitive and specific "labeling after recognition" sensing approach, where luminophore labeling occurred after the biological recognition. Taking the cutting enzyme caspase-3 as an example, we demonstrated the detection of its catalytic activity in solution and apoptotic cells using the tetrapeptide motif Asp-Glu-Val-Asp (DEVD) as the cleavable substrate, and an iridium(III) complex and a rhodamine derivative as the energy donor/acceptor pair. The DEVD tetrapeptide was modified with an azide and a GK-norbornylene groups at the amino and carboxyl terminuses, respectively, which allowed donor/acceptor bis-labeling via two independent catalysis-free bioorthogonal reactions. The phosphorescence lifetime of the iridium(III) complex was quenched upon bis-labeling owing to the intracellular FRET to the rhodamine derivative, and significantly elongated upon the peptide being catalytically cleaved by caspase-3. Interestingly, the sensitivity and efficiency of the lifetime responses were much higher in the "labeling after recognition" sensing approach. Molecular docking analysis showed that the steric hindrance and nonspecific interactions partially inhibited the biological recognition of the DEVD substrate by caspase-3. The imaging of the catalytic activity of caspase-3 in apoptotic cells was demonstrated via photoluminescence lifetime imaging microscopy. Lifetime analysis not only confirmed the occurrence of intracellular bioorthogonal bis-labeling and catalytic cleavage, but also showed the extent to which the two dynamic processes occurred.

12.
Genome Biol ; 20(1): 267, 2019 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-31810476

RESUMO

BACKGROUND: Chromosome evolution is an important driver of speciation and species evolution. Previous studies have detected chromosome rearrangement events among different Carnivora species using chromosome painting strategies. However, few of these studies have focused on chromosome evolution at a nucleotide resolution due to the limited availability of chromosome-level Carnivora genomes. Although the de novo genome assembly of the giant panda is available, current short read-based assemblies are limited to moderately sized scaffolds, making the study of chromosome evolution difficult. RESULTS: Here, we present a chromosome-level giant panda draft genome with a total size of 2.29 Gb. Based on the giant panda genome and published chromosome-level dog and cat genomes, we conduct six large-scale pairwise synteny alignments and identify evolutionary breakpoint regions. Interestingly, gene functional enrichment analysis shows that for all of the three Carnivora genomes, some genes located in evolutionary breakpoint regions are significantly enriched in pathways or terms related to sensory perception of smell. In addition, we find that the sweet receptor gene TAS1R2, which has been proven to be a pseudogene in the cat genome, is located in an evolutionary breakpoint region of the giant panda, suggesting that interchromosomal rearrangement may play a role in the cat TAS1R2 pseudogenization. CONCLUSIONS: We show that the combined strategies employed in this study can be used to generate efficient chromosome-level genome assemblies. Moreover, our comparative genomics analyses provide novel insights into Carnivora chromosome evolution, linking chromosome evolution to functional gene evolution.

13.
Bioinformatics ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31790141

RESUMO

MOTIVATION: Threading is one of the most effective methods for protein structure prediction. In recent years, the increasing accuracy in protein contact map prediction opens a new avenue to improve the performance of threading algorithms. Several preliminary studies suggest that with predicted contacts, the performance of threading algorithms can be improved greatly. There is still much room to explore to make better use of predicted contacts. RESULTS: We have developed a new contact-assisted threading algorithm named CATHER using both conventional sequential profiles and contact map predicted by a deep learning-based algorithm. Benchmark tests on an independent test set and the CASP12 targets demonstrated that CATHER made significant improvement over other methods which only use either sequential profile or predicted contact map. Our method was ranked at the top 10 among all 39 participated server groups on the 32 free modeling targets in the blind tests of the CASP13 experiment. These data suggest that it is promising to push forward the threading algorithms by using predicted contacts. AVAILABILITY AND IMPLEMENTATION: http://yanglab.nankai.edu.cn/CATHER/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

14.
Aging (Albany NY) ; 112019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31790362

RESUMO

To provide comprehensive estimates of the global, regional, and national burden of infertility from 1990 to 2017, using findings from a 2017 study on the global burden of disease (GBD), we assessed the burden of infertility in 195 countries and territories from 1990 to 2017. DisMod-MR 2.1 is a Bayesian meta-regression method that estimates non-fatal outcomes using sparse and heterogeneous epidemiological data. Globally, the age-standardized prevalence rate of infertility increased by 0.370% per year for females and 0.291% per year for males from 1990 to 2017. Additionally, age-standardized disability-adjusted life-years (DALYs) of infertility increased by 0.396% per year for females and 0.293% per year for males during the observational period. An increasing trend to these burden estimates was observed throughout the all socio-demographic index (SDI) countries. Interestingly, we found that high SDI countries had the lowest level of prevalence and DALYs in both genders. However, the largest increasing trend was observed in high-SDI countries for females. By contrast, low-SDI countries had the largest increasing trend in males. Negative associations were observed between these burden estimates and the SDI level. The global disease burden of infertility has been increasing throughout the period from 1990 to 2017.

15.
Mol Cancer ; 18(1): 174, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791342

RESUMO

BACKGROUND: Long noncoding RNAs (lncRNAs) play nonnegligible roles in the epigenetic regulation of cancer cells. This study aimed to identify a specific lncRNA that promotes the colorectal cancer (CRC) progression and could be a potential therapeutic target. METHODS: We screened highly expressed lncRNAs in human CRC samples compared with their matched adjacent normal tissues. The proteins that interact with LINRIS (Long Intergenic Noncoding RNA for IGF2BP2 Stability) were confirmed by RNA pull-down and RNA immunoprecipitation (RIP) assays. The proliferation and metabolic alteration of CRC cells with LINRIS inhibited were tested in vitro and in vivo. RESULTS: LINRIS was upregulated in CRC tissues from patients with poor overall survival (OS), and LINRIS inhibition led to the impaired CRC cell line growth. Moreover, knockdown of LINRIS resulted in a decreased level of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), a newly found N6-methyladenosine (m6A) 'reader'. LINRIS blocked K139 ubiquitination of IGF2BP2, maintaining its stability. This process prevented the degradation of IGF2BP2 through the autophagy-lysosome pathway (ALP). Therefore, knockdown of LINRIS attenuated the downstream effects of IGF2BP2, especially MYC-mediated glycolysis in CRC cells. In addition, the transcription of LINRIS could be inhibited by GATA3 in CRC cells. In vivo experiments showed that the inhibition of LINRIS suppressed the proliferation of tumors in orthotopic models and in patient-derived xenograft (PDX) models. CONCLUSION: LINRIS is an independent prognostic biomarker for CRC. The LINRIS-IGF2BP2-MYC axis promotes the progression of CRC and is a promising therapeutic target.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31791639

RESUMO

AIMS: The prevalence of metabolic syndrome (MetS) has been increasing in recent years. Investigation of whether consumption of legumes as a part of healthy diet could reduce the odds of MetS has led to inconsistent conclusions. Here, we performed the first meta-analysis of observational studies to analyze the association between legume consumption and prevalence of MetS. DATA SYNTHESIS: PubMed, EMBASE, and Web of Science databases were searched to identify observational studies up to June 1, 2019. We extracted data from the studies included and performed quality assessments. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Publication bias and subgroup and sensitivity analyses were also performed. We finally included four cross-sectional studies, two cohort studies, and one case-control study involving 56,028 participants. The summary OR revealed no statistically significant association between legume consumption and odds of MetS (OR = 0.93, 95% CI = 0.76-1.12, I2 = 73.5%). Subgroup analysis of study characteristics and adjustment for confounding along with sensitivity analyses revealed no statistically significant differences. No evidence of publication bias was detected. CONCLUSION: Legume consumption is not associated with the odds of MetS. These findings require validation in well-designed cohort studies and randomized clinical trials with accurate measurement of legume intake and strict control of confounders. REGISTRATION: This study was registered with the International Prospective Register of Systematic Reviews (registration number: CRD42019131777).

17.
Onco Targets Ther ; 12: 9513-9525, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31807027

RESUMO

Background: Accumulating evidences suggest that microRNAs (miRNAs) play key roles in mediating glioblastoma progression. Decreased expression of miR-152-3p was reported in several cancer types including glioblastoma. Methods: The sensitivity of glioblastoma cells to cisplatin was assessed by the cell counting kit-8 assay and flow cytometry analysis. The expression of miR-152-3p was determined by RT-qPCR method. Bioinformatic analysis, dual luciferase reporter assay and Western blot were used to explore the target gene of miR-152-3p. The association between miR-152-3p and SOS1 was confirmed in glioblastoma tissues by Pearson correlation analysis. Results: In the current study, we discovered that overexpression of miR-152-3p increased cisplatin sensitivity while inhibition of miR-152-3p decreased cisplatin sensitivity in glioblastoma cells (T98G and U87). In addition, miR-152-3p augmented cell apoptosis induced by cisplatin treatment. It was further predicted and validated that SOS1, a protein involved in regulating chemotherapy sensitivity, was a direct target gene of miR-152-3p. SOS1 was proven to suppress the cytotoxic effect of cisplatin in glioblastoma. Transfection of recombinant SOS1 could effectively reverse the increased cisplatin sensitivity induced by miR-152-3p overexpression in T98G. Furthermore, overexpression of SOS1 reduced the percentage of apoptotic cells increased by miR-152-3p mimic in the presence of cisplatin in T98G. More importantly, a significant negative correlation between miR-152-3p levels and SOS1 levels was observed in glioblastoma tissues collected from 40 patients. Conclusion: Our study identified miR-152-3p as a chemotherapy sensitizer in glioblastoma.

18.
Hypertension ; : HYPERTENSIONAHA11913504, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31838909

RESUMO

Evidence on the associations between airborne particulates of diameter ≤1 µm (PM1) and airborne particulates of diameter ≤2.5 µm (PM2.5) and childhood blood pressure (BP) is scarce. To help to address this literature gap, we conducted a study to explore the associations in Chinese children. Between 2012 and 2013, we recruited 9354 children, aged 5 to 17 years, from 62 schools in 7 northeastern Chinese cities. We measured their BP with a mercury sphygmomanometer. We used a spatiotemporal model to estimate daily ambient PM1 and PM2.5 exposures, which we assigned to participants' home addresses. Associations between particulate matter exposure and BP were evaluated with generalized linear mixed regression models. The findings indicated that exposure to each 10 mg/m3 greater PM1 was significantly associated with 2.56 mm Hg (95% CI, 1.47-3.65) higher systolic BP and 61% greater odds for hypertension (odds ratio=1.61 [95% CI, 1.18-2.18]). PM1 appears to play an important role in associations reported between PM2.5 exposure and BP, and we found that the ambient PM1/PM2.5 ratio (range, 0.80-0.96) was associated with BP and with hypertension. Age and body weight modified associations between air pollutants and BP (P<0.01), with stronger associations among younger (aged ≤11 years) and overweight/obese children. This study provides the first evidence that long-term exposure to PM1 is associated with hypertension in children, and that PM1 might be a leading contributor to the hypertensive effect of PM2.5. Researchers and policy makers should pay closer attention to the potential health impacts of PM1.

19.
Eurographics Workshop Vis Comput Biomed ; 38(3): 467-478, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31840002

RESUMO

We present a general high-performance technique for ray tracing generalized tube primitives. Our technique efficiently supports tube primitives with fixed and varying radii, general acyclic graph structures with bifurcations, and correct transparency with interior surface removal. Such tube primitives are widely used in scientific visualization to represent diffusion tensor imaging tractographies, neuron morphologies, and scalar or vector fields of 3D flow. We implement our approach within the OSPRay ray tracing framework, and evaluate it on a range of interactive visualization use cases of fixed- and varying-radius streamlines, pathlines, complex neuron morphologies, and brain tractographies. Our proposed approach provides interactive, high-quality rendering, with low memory overhead.

20.
Environ Sci Technol ; 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31825640

RESUMO

With the potential continuous application of mono- or few-layered black phosphorus (BP) in electronic, photonic, therapeutic and environmental fields, the possible side effects of BP on aquatic organisms after release into natural water are of great concern. We investigated the potential toxicity of BP on the unicellular organism, Tetrahymena thermophila (T. thermophila). After the exposure for 8 h at 10 µg/mL, the reproduction of T. thermophila significantly decreased by 46.3%. Severe cell membrane and cilium damage were observed by scanning electron microscopy (SEM) upon treatment with BP. Based on bright-field microscopy and three-dimensional Raman imaging, we investigated the cellular uptake and translocation of BP within T. thermophila. It was observed that the engulfment of BP by T. thermophila was oral apparatus dependent, through which intracellular BP was then transported to the posterior end of T. thermophila by food vacuole packaging. Our study also revealed that BP induced the increase of intracellular reactive oxidant species and formed oxidative stress-dependent toxicity to T. thermophila. Our findings paved a way for better understanding the BP toxicityon aquatic organisms and its potential ecological risks.

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