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1.
Artigo em Inglês | MEDLINE | ID: mdl-34508561

RESUMO

OBJECTIVES: To explore the efficacy of plasma exchange (PE) therapy in refractory idiopathic inflammatory myopathy (IIM) patients with positive anti-signal recognition particle (SRP) antibody. METHODS: Nine refractory IIM patients with positive anti-SRP antibody were enrolled, who received PE therapy at Ruijin Hospital from Octobor 2017 to December 2020. The clinical manifestations, laboratory tests, chest CT and lower extremity MRI images before and after PE therapy were compared. The treatment response was evaluated by the 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) myositis response criteria. RESULTS: 88.9% (8/9) subjects had achieved improvement by 3 weeks after PE therapy, with 55.6% (5/9) minimal improvement and 33.3% (3/9) moderate improvement. There were statistically significant improvements between baseline and after PE therapy at 3 weeks on the core set measures: physician global activity, patient global activity, Health Assessment Questionnaire (HAQ), manual muscle testing (MMT), extramuscular disease activity, and muscle enzymes activity including creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST), except for alanine transaminase (ALT). Moreover, the chest CT showed regression of ground glass opacities and irregular linear opacities after PE therapy in four patients with interstitial lung disease. The MRI images of lower extremity in four patients showed reduction of muscle oedema after the therapy. CONCLUSION: PE therapy is effective for refractory IIM patients with positive anti-SRP antibody. It should be considered as an alternative treatment for those patients who are resistant to the combined therapy of glucocorticoids and immunosuppressive agents.

2.
Neurotoxicology ; 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34508789

RESUMO

Carbon black (CB) has been demonstrated to have adverse effects on the lung tissue. Few studies explored the effects of CB on the cerebellum, widely recognized to contribute to gait and balance coordination and timing in the motor domain. Some studies have reported that inflammatory response and damaged autophagy are important mechanisms of CB toxicity and can be repaired after the recovery. The present study aimed to determine whether long-term CB exposure could induce the inflammation and damaged autophagy of the cerebellum. The rats were randomly divided into four groups. The control group received the filtered air for 90 days; the carbon black (CB) group received CB particles for 90 days; the recovery (R) group received CB for 90 days and recovered for another 14 days; the recovery control (RC) group received filtered air for 104 days. The purpose of the R group was to test whether neuroinflammation and autophagy could be repaired after short-term recovery. The western blot and immunohistochemistry revealed that long-term CB exposure induced augmented level of pro-inflammatory cytokines (Interleukin-1ß, IL-1ß; Interleukin-6, IL-6; and Tumor Necrosis Factor-α, TNF-α) and anti-inflammatory cytokine (Interleukin-10, IL-10). The autophagic markers (Beclin1 and LC3) were increased in both CB group and R group. These findings clearly demonstrated that long-term CB exposure induced inflammation and autophagy in the cerebellum, which were not obviously changed after short-term recovery.

3.
Exp Eye Res ; 211: 108756, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34492282

RESUMO

The growth of the mouse eye and retina after birth is a dynamic, highly regulated process. In this study, we applied visible-light optical coherence tomography (vis-OCT), a non-invasive imaging technique, to examine developing retinal layer structures after eye-opening. We introduced a resampled circumpapillary B-scan averaging technique to improve the inter-layer contrast, enabling retinal layer thickness measurements as early as postnatal day 13 (P13) - right after eye-opening. We confirmed vis-OCT measurements using ex vivo confocal microscopy of retinal sections at different ages. Our results demonstrate that vis-OCT can visualize the developmental murine retinal layer structure in vivo, which offers us new opportunities to better characterize the pathological alterations in mouse models of developmental eye diseases.

4.
J Hazard Mater ; 416: 125862, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492810

RESUMO

Di (2-ethylhexyl) phthalate (DEHP) is widely used as a plastic additive and it could induce reproduction defects and fertility in mammals as environmental endocrine disruptor. However, the effects and potential mechanism of DEHP exposure during lactation stage on follicular development of offspring are still unclear. In this study, we found that the total primordial follicle number and antral follicles in the suckling of mice exposed to DEHP during lactation was significantly reduced. RNA-seq analysis results showed that the transcription levels of genes related to steroid production, ovarian hormone secretion and oxidative stress were significantly changed, which led to a decrease in 17ß-estradiol and an increase in oxidative stress. The proportion of DNA damage marker γH2AX in the ovary of female suckling exposed to DEHP was significantly increased. We also found an increase in the level of ovarian apoptosis, and the proliferation of ovarian granulosa cells was inhibited. These alterations also lead to abnormal spindle and chromosome misalignment during oocyte maturation. Overall, our data indicate that lactation exposure to DEHP can affect the secretion of hormones and the development of antral follicles in suckling mice by affecting the secretion pathways of ovarian hormone enzymes and oxidative stress pathway.


Assuntos
Dietilexilftalato , Ovário , Animais , Dietilexilftalato/toxicidade , Estradiol , Feminino , Lactação , Camundongos , Folículo Ovariano
5.
Food Chem ; 370: 131014, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34500288

RESUMO

Liquid foams are crucial to many food systems, yet improving their lifetime remains challenging. In this study, stable foams were prepared by protein networks in association with starch nanocrystals (SNCs). The protein networks were structured by simultaneous folding of hydrophobic rice proteins (RPs) and hydrophilic pea proteins (PPs) due to anti-solvent precipitation from an alkaline solution, forming amphiphilic binary nanostructures (RP-PPs) to facilitate foaming. Relying on polar groups of RP-PPs and SNCs, the two biopolymers spontaneously formed flexible but mechanically strong complexes (RP-PP@SNCs) via dipole-dipole interactions and hydrogen bonding. After high-speed frothing, liquid foams that can be stable for up to 4 days were agitated with coherent RP-PP@SNCs docking at the interface in addition to the formation of three-dimensional networks in the continuous phase, contributing to joint stabilization mechanisms of Pickering-type coverages and steric hindrance. This study presents a facile strategy for innovating novel stabilization protocols for liquid foams.

6.
Food Chem ; 370: 130989, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34509944

RESUMO

In order to help the poultry industry to generate higher quality products, the headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) technique was used to identify volatile substances formed during the processing of Dezhou braised chicken (DBC). A total of 37 volatile substances including aldehydes, alcohols, ketones, esters, terpenoids, furans and pyrazines were identified during DBC processing across seven sampling stages. The analyses identified 2-ethylhexanol as a key flavor chemical within the chicken carcasses, and found that ethyl acetate, 1-hexanol, 4-methyl-2-pentanone and 1-pentanol were mainly produced during the deep-frying stage of processing. Stewing with herbs and spices was found to be an important stage in the flavor impartation process. 2-Butanone, n-nonanal, heptanal and ethanol were positively related to processing stage 3, whereas processing stage 4 was characterized by ethyl propanoate, benzaldehyde, butyl acetate, 2-pentyl furan and 2-heptanone. The processing stages 5, 6 and 7 were not significantly different (P > 0.05) from each other.

7.
Gene ; : 145969, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34530084

RESUMO

As the largest energy storage reservoir, subcutaneous adipose tissue (SAT) stores excess lipids by adipocytes enlargement and/or recruitment of new precursor cells. Energy overload can cause ectopic fat deposition and metabolic diseases. In this study, 6814 differentially expressed genes (DEGs) were screened in goat subcutaneous preadipocytes and mature adipocytes by RNA-seq technique. The relative expression of the DEGs were verified by qPCR, such as PLIN2, MECR, ADCY7, PEBP1 and KLF5, and their expression level was found to be consistent with the trend of RNA-seq analysis. The KLF5 was selected for further functional verification. Overexpression of KLF5 promoted both the adipogenesis and the differentiation of preadipocytes, while the expression of preadipocyte marker gene: preadipocyte factor 1(Pref1) was decreased, as well as, peroxisome proliferator activation Receptor γ(PPARγ), CCAAT enhancer binding protein ß(C/EBPß) and Sterol regulatory element binding protein isoform 1(SREBP1) were increased. On the contrary, the interference of KLF5 could reduce adipogenesis, enhance the expression of Pref1, and reduce the expression of C/EBPß and SREBP1. Our research provides a basic reference for revealing the mechanism of subcutaneous adipocyte differentiation in goats.

8.
J Hazard Mater ; 423(Pt B): 127128, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34534804

RESUMO

Effectively harnessing renewable and inexhaustible solar radiation for energy conversion has attracted significant research interest in the past decade. Solar thermal conversion, as a ubiquitous phenomenon, can be implemented to evaporate water and concurrently boost photocatalytic performance for addressing freshwater scarcity and energy crisis. Most recently, solar water evaporation accompanied by photocatalytic degradation, sterilization, and hydrogen production has been proposed as a promising avenue to endow new vitality into the field of clean water and energy production. Driven by the advances of rationally designed solar-powered functional materials, a large variety of photothermal-coupled photocatalysis technologies have been exploited. In this context, it is imperative to summarize the recent progress and discuss the challenges in this multidisciplinary field. Herein, we overview photothermal materials based on various fundamental principles and highlight emerging applications in the areas of solar water evaporation, water purification, and solar-driven energy production. Furthermore, the challenges and perspectives toward both fundamental research and practical applications are also proposed. It is envisioned that this review can provide insightful suggestions to further advance the development of integrated solar thermal driven water evaporation and photocatalytic systems to fulfill concurrent energy conversion and environmental applications.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34520189

RESUMO

To diversify the motion modes of multifunctional soft robots capable of shape programming, we fabricate a biomimetic and programmable Ti3C2Tx MXene/low-density polyethylene (LDPE) bilayer actuator by spraying an aqueous dispersion of MXenes onto a plasma-activated LDPE film, followed by optimal thermal regulations. Because of the eminent light absorption and photothermal/electrothermal features of MXenes and the extremely mismatched thermal expansion coefficients between the two layers, the MXene/LDPE actuator can be sensitively driven by many stimuli of near-infrared light, electricity, and heat. The initial configuration of the bilayer actuator can be programmed by tuning the thermal regulation temperature, thereby assembling multiple actuation units to achieve biomimetic functions, such as artificial iris, mechanical arms, and flying birds. More importantly, in virtue of free shape cutting and programmable configuration, the MXene/LDPE bilayer actuator can perform untethered locomotion including crawling, rolling, and sailing. The soft robots can not only move on the ground in different forms but also sail on water along any designated routes and complete the surface cargo transportation driven by a near-infrared laser via the photothermal Marangoni effect. The shape-programmable methodology for the three amphibious motion modes lays foundations for wide applications of the MXene-based soft robots.

10.
Int J Cancer ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34520566

RESUMO

Elevated Epstein-Barr virus (EBV) DNA load is common in lymphomas. However, it remains unclear whether the disparity in viral load and its prognostic value in lymphomas are correlated with EBER status. In this retrospective multicenter study, we collected the data of pretreatment whole blood EBV DNA (pre-EBV DNA) and EBER status and evaluated their disparity and prognostic values in lymphomas. A total of 454 lymphoma patients from December 2014 to August 2020 were retrospectively retrieved. Mann-Whitney U test, Kruskal-Wallis test, and Bonferroni's adjustment were used to explore the disparity of EBV DNA and EBER status in lymphomas. Time-dependent receiver operating characteristic analysis and MaxStat analysis were used to determine optimal cut-off points of pre-EBV DNA load. Univariable and multivariable Cox proportional hazards models were established for the estimation of prognostic factors. The positive rate of EBV-DNA in NKTL patients was higher than that in DLBCL, FL, and HL patients, and the median positive pre-EBV copy number of NKTL was also higher than that of FL and DLBCL. EBV-DNA could clearly distinguish the prognosis of DLBCL, NKTL, HL and PTCL, and the integration of EBER status and EBV DNA could differentiate the prognosis of HL patients. Multivariable results revealed that pre-EBV DNA load had an effect on the prognosis of NKTL, FL and DLBCL. The status of pre-EBV DNA and EBER were disparate. Whole blood pre-EBV DNA predicted the prognosis of lymphomas, and the combination of EBV and EBER status could differentiate the prognosis of HL. This article is protected by copyright. All rights reserved.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34520665

RESUMO

Active targeted therapy for bowel cancer using untethered microrobots has attracted extensive attention. However, traditional microrobots face challenges, such as issues of mobility, biocompatibility, drug loading, sustained-release capabilities, and targeting accuracy. Here, we propose an untethered triple-configurational magnetic robot (TCMR) that is composed of three geometrically nested parts: actuation and guarding, anchoring and seeding, and drug release part. A targeting magnetic driving system actuates the TCMR along the predetermined trajectory to the target position. The pH-sensitive actuation and guarding part formed by electrodeposition is degraded in the intestinal environment and separates from the two other parts. A majority of magnetic nanoparticles encapsulated in this part are retrieved. The anchoring and seeding part anchors the lesion area and seeds the drug release part in the gaps of intestinal villi by hydrolysis. Ultimately, the drug release part containing the therapeutic completes the sustained release to prolong the duration of the therapeutic agent. Cytotoxicity and therapeutic tests reveal that TCMRs are biocompatible and suitable for targeted therapy and have good therapeutic performance. The newly designed TCMR will provide new ideas for targeted therapy, thus expanding the application scope of robotics technology in the biomedical field.

12.
Acta Pharmacol Sin ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34522005

RESUMO

Behavioral sensitization is a progressive increase in locomotor or stereotypic behaviours in response to drugs. It is believed to contribute to the reinforcing properties of drugs and to play an important role in relapse after cessation of drug abuse. However, the mechanism underlying this behaviour remains poorly understood. In this study, we showed that mTOR signaling was activated during the expression of behavioral sensitization to cocaine and that intraperitoneal or intra-nucleus accumbens (NAc) treatment with rapamycin, a specific mTOR inhibitor, attenuated cocaine-induced behavioural sensitization. Cocaine significantly modified brain lipid profiles in the NAc of cocaine-sensitized mice and markedly elevated the levels of phosphatidylinositol-4-monophosphates (PIPs), including PIP, PIP2, and PIP3. The behavioural effect of cocaine was attenuated by intra-NAc administration of LY294002, an AKT-specific inhibitor, suggesting that PIPs may contribute to mTOR activation in response to cocaine. An RNA-sequencing analysis of the downstream effectors of mTOR signalling revealed that cocaine significantly decreased the expression of SynDIG1, a known substrate of mTOR signalling, and decreased the surface expression of GluA2. In contrast, AAV-mediated SynDIG1 overexpression in NAc attenuated intracellular GluA2 internalization by promoting the SynDIG1-GluA2 interaction, thus maintaining GluA2 surface expression and repressing cocaine-induced behaviours. In conclusion, NAc SynDIG1 may play a negative regulatory role in cocaine-induced behavioural sensitization by regulating synaptic surface expression of GluA2.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34523095

RESUMO

Cr(VI), a serious threat to human health, widely exists in the effluents of various industrial processes. In this paper, the potential of industrial lignin for efficient removal of Cr(VI) from wastewater was systematically investigated, including pulping black liquor lignin (BLN), enzymolysis lignin (ELN), and SPORL pretreatment spent liquor (FS). The structure characterizations of three lignins were investigated by thermogravimetry (TG), Fourier transform infrared (FTIR) spectroscopy, Brunauer-Emmett-Teller (BET) surface area measurement, scanning electron microscope (SEM), and X-ray photoelectron spectroscopy (XPS). Among these three lignins, BLN showed the highest adsorption amount of Cr(VI) and good selectivity in wastewater simulation. According to the Langmuir model, the calculated maximum adsorption amount of Cr(VI) on ELN, BLN, and FS was 801.57, 864.30, and 642.26 mg g-1, respectively. The adsorption of Cr(VI) by industrial lignins was a chemisorption process, during which Cr(VI) was reduced to low-toxic Cr(III). This paper provided a promising application for the effective utilization of industrial lignins.

14.
J Agric Food Chem ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34523917

RESUMO

Abundant conjugated linoleic acid (CLA) producers exist among Bifidobacterium species. This CLA production is related to the mitigation of LA toxicity. However, there is still a lack of information on the metabolic response underlying this detoxification strategy. In this study, six bifidobacteria strains belonging to three different species were used to characterize growth and CLA accumulation in the presence of LA. A combination of non-targeted metabolomics techniques and biochemical indicators were used to explore metabolic profile changes in response to LA and the expression of important factors driving CLA production in Bifidobacterium species. The results suggested that free LA had growth inhibitory effects on bifidobacteria, resulting in a global metabolic stress response that caused metabolic reprogramming on all tested strains and promoted malondialdehyde production, inducing a redox imbalance. In particular, a strong decrease in reduced glutathione level was observed in Bifidobacterium breve CCFM683 [log2(FC) = -3.29]. Furthermore, LA-induced oxidative stress is an important factor driving high CLA production in certain strains.

15.
Chem Asian J ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519418

RESUMO

Bistable switches (electrical switching between "ON" and "OFF" bistable states) have gradually developed into an ideal category of highly intelligent materials, due to their significant application in optical technology, signal processors, data storage and other switchable media applications in the field of electrical devices. Here, we successfully designed and synthesized [(FC 6 H 4 C 2 H 4 NH 3 ) 2 MCl 4 ] n (FC 6 H 4 C 2 H 4 NH 3 + )=deprotonated 4-fluoro- phenethylamine; M = Cd ( 1 ), Mn ( 2 )), which realized the coupling of thermo-dielectric switching characteristics, semi-conductor characteristics and photo-luminescent properties. DSC (Differential scanning calorimetry) and dielectric measurements show that 1 is a sensitive dielectric bistable switch between the high dielectric (ON) and low dielectric (OFF) states. The temperature-variable single crystal structure shows that the both 1 and 2 undergo a high-temperature reversible phase transition around 383 K/380 K, which is caused by the order-disordered transformation of organic cations and the slight distortion of the inorganic framework. In particular, 1 shows outstanding switchable dielectric behavior and semiconducting properties. Further, 1 and 2 emit strong green and yellow luminescence at 527 and 595 nm respectively.

16.
Microbiome ; 9(1): 180, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34470652

RESUMO

BACKGROUND: Probiotics have been used to regulate the gut microbiota and physiology in various contexts, but their precise mechanisms of action remain unclear. RESULTS: By population genomic analysis of 418 Bifidobacterium longum strains, including 143 newly sequenced in this study, three geographically distinct gene pools/populations, BLAsia1, BLAsia2, and BLothers, were identified. Genes involved in cell wall biosynthesis, particularly peptidoglycan biosynthesis, varied considerably among the core genomes of the different populations, but accessory genes that contributed to the carbohydrate metabolism were significantly distinct. Although active transmission was observed inter-host, inter-country, inter-city, intra-community, and intra-family, a single B. longum clone seemed to reside within each individual. A significant negative association was observed between host age and relative abundance of B. longum, while there was a strong positive association between host age and strain genotype [e.g., single nucleotide polymorphisms in the arginine biosynthesis pathway]. Further animal experiments performed with the B. longum isolates via using a D-galactose-induced aging mouse model supported these associations, in which B. longum strains with different genotypes in arginine biosynthesis pathway showed divergent abilities on protecting against host aging possibly via their different abilities to modify the metabolism of gut microbes. CONCLUSIONS: This is the first known example of research on the evolutionary history and transmission of this probiotic species. Our results propose a new mechanistic insight for promoting host longevity via the informed use of specific probiotics or molecules. Video abstract.


Assuntos
Bifidobacterium longum , Microbioma Gastrointestinal , Probióticos , Sulfaleno , Envelhecimento , Animais , Galactose , Microbioma Gastrointestinal/genética , Humanos , Camundongos
17.
Sensors (Basel) ; 21(17)2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34502853

RESUMO

Transcranial focused ultrasound (tFUS) has great potential in brain imaging and therapy. However, the structural and acoustic differences of the skull will cause a large number of technical problems in the application of tFUS, such as low focus energy, focal shift, and defocusing. To have a comprehensive understanding of the skull effect on tFUS, this study investigated the effects of the structural parameters (thickness, radius of curvature, and distance from the transducer) and acoustic parameters (density, acoustic speed, and absorption coefficient) of the skull model on tFUS based on acrylic plates and two simulation methods (self-programming and COMSOL). For structural parameters, our research shows that as the three factors increase the unit distance, the attenuation caused from large to small is the thickness (0.357 dB/mm), the distance to transducer (0.048 dB/mm), and the radius of curvature (0.027 dB/mm). For acoustic parameters, the attenuation caused by density (0.024 dB/30 kg/m3) and acoustic speed (0.021 dB/30 m/s) are basically the same. Additionally, as the absorption coefficient increases, the focus acoustic pressure decays exponentially. The thickness of the structural parameters and the absorption coefficient of the acoustic parameters are the most important factors leading to the attenuation of tFUS. The experimental and simulation trends are highly consistent. This work contributes to the comprehensive and quantitative understanding of how the skull influences tFUS, which further enhances the application of tFUS in neuromodulation research and treatment.


Assuntos
Crânio , Transdutores , Acústica , Encéfalo , Simulação por Computador , Crânio/diagnóstico por imagem
18.
Nanoscale Horiz ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34490855

RESUMO

Low dimensional tellurium is currently of great interest for potential electronic applications due to the experimentally observed Weyl fermions and the excellent carrier mobility, on/off ratios and current-carrying capacity in devices. However, the optical properties of Te nanostructures are not well explored, especially in the field of nonlinear optics. Here, we prepared a series of Te nanostructures by electrochemical exfoliation and liquid phase exfoliation methods, including one-dimensional (1D) Te nanowires (NWs), quasi-1D Te nanorods (NRs), zero-dimensional (0D) Te nanodots (NDs) and two-dimensional (2D) Te nanosheets (NSs). Femtosecond Z-scan measurements reveal unique dimension-dependent nonlinear optical (NLO) properties. 1D Te NWs and quasi-1D Te NRs exhibited higher saturable absorption behavior than 0D Te nanostructures, while the 2D Te NSs are a high performance optical limiting material. Ultrafast transient absorption spectroscopy revealed the dimension-dependent exciton dynamics. The reverse saturable absorption of 2D Te NSs is derived from faster exciton relaxation and stronger excited state absorption. This work paves the way for the design of saturable absorbers with high performance and broadens the application of 2D Te in the field of laser protection and other novel ultrafast photonics.

19.
Medicine (Baltimore) ; 100(35): e27187, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477178

RESUMO

ABSTRACT: It is well-known that microRNAs are able to regulate the expression of target mRNAs through complementary base-pairing to their 3'-untranslated regions (3'UTR) sequences. This study aimed to investigate whether single nucleotide polymorphisms resided in the 3'UTR sequences in patients with chronic hepatitis B viruses (HBV) infection are associated with the development and metastasis of hepatocellular carcinoma (HCC). Seventeen single nucleotide polymorphisms in the 3'UTR sequence of 10 genes regulated or affected by hepatitis B virus X protein were found by bioinformatics methods. Two hundred fifteen patients with HBV-related HCC and 216 patients with chronic HBV infection were recruited. Through case-control study, only found that the von Hippel-Lindau gene rs1642742 (G>A) may be associated with the occurrence and metastasis of HCC. The ORs of the frequencies of rs1642742 A allele versus G allele were 1.424 (P = .038, 95% confidence interval [CI] = 1.019-1.989) between HBV-related HCC and chronic HBV infection group and were 2.004 (P = .037, 95%CI = 1.031-3.895) between tumor metastasis and non-metastasis group, respectively. Through multivariate regression analysis, we also found that rs1642742 AA genotype was an independent risk factor for tumor metastasis (odds ratio = 2.227, 95% CI = 1.043-4.752, P = .038) in HBV-related HCC group. Our study suggested that Von Hippel-Lindau rs1642742 contributed to susceptibility to developing HCC and correlated with tumor metastasis.


Assuntos
Carcinoma Hepatocelular/genética , Hepatite B Crônica/complicações , Neoplasias Hepáticas/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Adulto , Carcinoma Hepatocelular/virologia , Feminino , Humanos , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Polimorfismo de Nucleotídeo Único
20.
Front Immunol ; 12: 691811, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489938

RESUMO

The glioma tumor microenvironment (TME), composed of several noncancerous cells and biomolecules is known for its complexity of cancer-immune system interaction. Given that, novel risk signature is required for predicting glioma patient responses to immunotherapy. In this study, we systematically evaluated the TME infiltration pattern of 2877 glioma samples. TME phenotypes were determined using the Partitioning Around Medoid method. Machine learning including SVM-RFE and Principal component analysis (PCA) were used to construct a TME scoring system. A total of 857 glioma samples from four datasets were used for external validation of the TME-score. The correlation of TME phenotypes and TME-scores with diverse clinicopathologic characteristics, genomic features, and immunotherapeutic efficacy in glioma patients was determined. Immunohistochemistry staining for the M2 macrophage marker CD68 and CD163, mast cell marker CD117, neutrophil marker CD66b, and RNA sequencing of glioma samples from the XYNS cohort were performed. Two distinct TME phenotypes were identified. High TME-score correlated with a high number of immune infiltrating cells, elevated expression of immune checkpoints, increased mutation rates of oncogenes, and poor survival of glioma patients. Moreover, high TME-score exhibited remarkable association with multiple immunomodulators that could potentially mediate immune escape of cancer. Thus, the TME-score showed the potential to predict the efficacy of anti-PD-1 immunotherapy. Univariate and multivariate analyses demonstrated the TME-score to be a valuable prognostic biomarker for gliomas. Our study demonstrated that TME could potentially influence immunotherapy efficacy in melanoma patients whereas its role in immunotherapy of glioma patients remains unknown. Therefore, a better understanding of the TME landscape in gliomas would promote the development of novel immunotherapy strategies against glioma.

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