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1.
Nanomaterials (Basel) ; 11(3)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808713

RESUMO

Controllable growth of wafer-scale in-plane nanowires (NWs) is a prerequisite for achieving addressable and scalable NW-based quantum devices. Here, by introducing molecular beam epitaxy on patterned Si structures, we demonstrate the wafer-scale epitaxial growth of site-controlled in-plane Si, SiGe, and Ge/Si core/shell NW arrays on Si (001) substrate. The epitaxially grown Si, SiGe, and Ge/Si core/shell NW are highly homogeneous with well-defined facets. Suspended Si NWs with four {111} facets and a side width of about 25 nm are observed. Characterizations including high resolution transmission electron microscopy (HRTEM) confirm the high quality of these epitaxial NWs.

2.
Cancers (Basel) ; 13(6)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809063

RESUMO

The novel coronavirus SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Severely symptomatic COVID-19 is associated with lung inflammation, pneumonia, and respiratory failure, thereby raising concerns of elevated risk of COVID-19-associated mortality among lung cancer patients. Angiotensin-converting enzyme 2 (ACE2) is the major receptor for SARS-CoV-2 entry into lung cells. The single-cell expression landscape of ACE2 and other SARS-CoV-2-related genes in pulmonary tissues of lung cancer patients remains unknown. We sought to delineate single-cell expression profiles of ACE2 and other SARS-CoV-2-related genes in pulmonary tissues of lung adenocarcinoma (LUAD) patients. We examined the expression levels and cellular distribution of ACE2 and SARS-CoV-2-priming proteases TMPRSS2 and TMPRSS4 in 5 LUADs and 14 matched normal tissues by single-cell RNA-sequencing (scRNA-seq) analysis. scRNA-seq of 186,916 cells revealed epithelial-specific expression of ACE2, TMPRSS2, and TMPRSS4. Analysis of 70,030 LUAD- and normal-derived epithelial cells showed that ACE2 levels were highest in normal alveolar type 2 (AT2) cells and that TMPRSS2 was expressed in 65% of normal AT2 cells. Conversely, the expression of TMPRSS4 was highest and most frequently detected (75%) in lung cells with malignant features. ACE2-positive cells co-expressed genes implicated in lung pathobiology, including COPD-associated HHIP, and the scavengers CD36 and DMBT1. Notably, the viral scavenger DMBT1 was significantly positively correlated with ACE2 expression in AT2 cells. We describe normal and tumor lung epithelial populations that express SARS-CoV-2 receptor and proteases, as well as major host defense genes, thus comprising potential treatment targets for COVID-19 particularly among lung cancer patients.

3.
Int Immunopharmacol ; 96: 107554, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33812257

RESUMO

Natural polysaccharides and their derivatives have attracted academic attention due to their extensive physiological activities. However, the hepatoprotective effects against carbon tetrachloride (CCl4) toxicity have not been well elucidated. The objectives of this study were to characterize the structural properties of sulfated Ganoderma applanatum residue polysaccharides (SGRP) and to evaluate their inhibitory effects on liver fibrosis caused by oxidative stress and inflammation. Our in vivo study showed that SGRP was hepatoprotective in CCl4-induced chronic liver injury mice. It reduced the histopathological damages, down-regulated CYP2E1 (cytochrome P450 2E1) expression, reduced serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, improved the anti-oxidative and anti-inflammatory properties, inhibited TLR4/NF-κB signaling pathway, and reduced the release of inflammatory cytokines. The structural studies indicated that SGRP is a heteropolysaccharide with 7.8% sulfur content and α-linked residue. Our study projects SGRP as a potential candidate in anti-fibrosis treatment by using it as a food supplement or in medicines produced by pharmaceutical industries.

4.
Med Sci Monit ; 27: e929558, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33758160

RESUMO

BACKGROUND Gastric cancer is the most common gastrointestinal tumor, and the rates of recurrence and metastasis are high. Research results on molecular biomarkers used for prognosis of gastric cancer remain inconclusive. This study aimed to explore the gene expression module of gastric cancer and to determine potential prognostic biomarkers. MATERIAL AND METHODS Three microarray datasets (GSE13911, GSE79973, and GSE29272) from Gene Expression Omnibus (GEO), including 206 pairs of gastric tumors and adjacent normal samples, were used for analysis of differentially expressed genes (DEGs). The 3 microarray datasets yielded 144 genes associated with the progression and prognosis of gastric cancer. After this, a risk score model was developed for result validation using an independent dataset from The Cancer Genome Atlas. RESULTS The validation of the independent dataset showed significantly increased NID2, SPARC, and MFAP2 expression in gastric tumor tissues, which were associated with poor outcomes in gastric cancer patients. Moreover, the high risk score obtained was associated with poor overall survival (HR: 1.787; 1.069-2.986; P=0.027). Subgroup analyses revealed that these significant prognostic values were detected in patients aged <65.0 years, tumors in the antrum/distal colon, grade 3 tumors, or TNM-M0 stages of cancer. CONCLUSIONS The findings of this study show that NID2, SPARC, and MFAP2 are upregulated in gastric tumor tissues and are significantly associated with poor overall survival. Therefore, the predictive values of the risk score model employed for the prognosis of gastric cancer could be improved by using these 3 upregulated DEGs.

5.
Immunity ; 54(3): 586-602.e8, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33691136

RESUMO

To identify disease-relevant T cell receptors (TCRs) with shared antigen specificity, we analyzed 778,938 TCRß chain sequences from 178 non-small cell lung cancer patients using the GLIPH2 (grouping of lymphocyte interactions with paratope hotspots 2) algorithm. We identified over 66,000 shared specificity groups, of which 435 were clonally expanded and enriched in tumors compared to adjacent lung. The antigenic epitopes of one such tumor-enriched specificity group were identified using a yeast peptide-HLA A∗02:01 display library. These included a peptide from the epithelial protein TMEM161A, which is overexpressed in tumors and cross-reactive epitopes from Epstein-Barr virus and E. coli. Our findings suggest that this cross-reactivity may underlie the presence of virus-specific T cells in tumor infiltrates and that pathogen cross-reactivity may be a feature of multiple cancers. The approach and analytical pipelines generated in this work, as well as the specificity groups defined here, present a resource for understanding the T cell response in cancer.

6.
Arch Med Res ; 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33653596

RESUMO

OBJECTIVE: The early symptoms of nasopharyngeal carcinoma (NPC) are not obvious, and it is difficult to make early diagnosis. A case-control study was conducted to identify potential biomarkers and established a diagnosis model for nasopharyngeal carcinoma. METHODS: Plasma samples of 131 cases of NPC and 132 cases of healthy individuals were incubated with the Ray Biotech Human Lung Cancer IgG Autoantibody Detection Array G1, and signal values were used to develop a risk prediction model for NPC diagnosis. RESULTS: Of the 30 autoantibodies, high expression of MAGE-A4, NY-ESO-1, HuD, Survivin, IMDH2, Ubiquilin-1, IMP1, PGP9.5, IMP3, C-Myc and low expression of Cyclin B1 were potential biomarkers for NPC diagnosis (p <0.05), among which Survivin, MAGE-A4 and IMP3 shows higher AUC of 0.674, 0.652 and 0.650 respectively, the specificity of them was 89.39% (95% CI: 82.85-94.08%), 90.15% (95% CI: 83.75-94.65%) and 88.64% (81.95-93.50%).The risk probability analysis for NPC diagnosis based on the panel of Cyclin B1, NY-ESO-1, Survivin, and IMP3 displayed the best diagnosis performance with an AUC of 0.779, p (Yi = 1) = 1/(1+EXP[8.316+1.672*CyclinB1-1.152*NY-ESO-1-2.052*Survivin-0.950*IMP3]), the specificity of that was 86.36% (95% CI: 79.31-91.71%). CONCLUSIONS: Our findings demonstrated that the panel of Cyclin B1, NY-ESO-1, Survivin, and IMP3 has a good performance in the detection of NPC, and all 11 autoantibodies may also have a certain significance for the prognosis of NPC.

7.
J Immunol Res ; 2021: 6696606, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33748291

RESUMO

Background: Ganoderma lucidum has certain components with known pharmacological effects, including strengthening immunity and anti-inflammatory activity. G. lucidum seeds inherit all its biological characteristics. G. lucidum spore polysaccharide (GLSP) is the main active ingredient to enhance these effects. However, its specific biological mechanisms are not exact. Our research is aimed at revealing the specific biological mechanism of GLSP to enhance immunity and inhibit the growth of H22 hepatocellular carcinoma cells. Methods: We extracted primary macrophages (Mø) from BALB/c mice and treated them with GLSP (800 µg/mL, 400 µg/mL, and 200 µg/mL) to observe its effects on macrophage polarization and cytokine secretion. We used GLSP and GLSP-intervened macrophage supernatant to treat H22 tumor cells and observed their effects using MTT and flow cytometry. Moreover, real-time fluorescent quantitative PCR and western blotting were used to observe the effect of GLSP-intervened macrophage supernatant on the PI3K/AKT and mitochondrial apoptosis pathways. Results: In this study, GLSP promoted the polarization of primary macrophages to M1 type and the upregulation of some cytokines such as TNF-α, IL-1ß, IL-6, and TGF-ß1. The MTT assay revealed that GLSP+Mø at 400 µg/mL and 800 µg/mL significantly inhibited H22 cell proliferation in a dose-dependent manner. Flow cytometry analysis revealed that GLSP+Mø induced apoptosis and cell cycle arrest at the G2/M phase, associated with the expression of critical genes and proteins (PI3K, p-AKT, BCL-2, BAX, and caspase-9) that regulate the PI3K/AKT pathway and apoptosis. GLSP reshapes the tumor microenvironment by activating macrophages, promotes the polarization of primary macrophages to M1 type, and promotes the secretion of various inflammatory factors and cytokines. Conclusion: Therefore, as a natural nutrient, GLSP is a potential agent in hepatocellular carcinoma cell treatment and induction of apoptosis.

9.
Nat Med ; 27(3): 504-514, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33603241

RESUMO

Ipilimumab improves clinical outcomes when combined with nivolumab in metastatic non-small cell lung cancer (NSCLC), but its efficacy and impact on the immune microenvironment in operable NSCLC remain unclear. We report the results of the phase 2 randomized NEOSTAR trial (NCT03158129) of neoadjuvant nivolumab or nivolumab + ipilimumab followed by surgery in 44 patients with operable NSCLC, using major pathologic response (MPR) as the primary endpoint. The MPR rate for each treatment arm was tested against historical controls of neoadjuvant chemotherapy. The nivolumab + ipilimumab arm met the prespecified primary endpoint threshold of 6 MPRs in 21 patients, achieving a 38% MPR rate (8/21). We observed a 22% MPR rate (5/23) in the nivolumab arm. In 37 patients resected on trial, nivolumab and nivolumab + ipilimumab produced MPR rates of 24% (5/21) and 50% (8/16), respectively. Compared with nivolumab, nivolumab + ipilimumab resulted in higher pathologic complete response rates (10% versus 38%), less viable tumor (median 50% versus 9%), and greater frequencies of effector, tissue-resident memory and effector memory T cells. Increased abundance of gut Ruminococcus and Akkermansia spp. was associated with MPR to dual therapy. Our data indicate that neoadjuvant nivolumab + ipilimumab-based therapy enhances pathologic responses, tumor immune infiltrates and immunologic memory, and merits further investigation in operable NSCLC.

10.
Int J Pharm ; 597: 120374, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33581272

RESUMO

Puerarin (PUE), a bioactive flavonoid from the plant Pueraria lobata, exists in two hydrated forms: monohydrate (PUEMH) and dihydrate (PUEDH). The aim of the present work was to explore the thermodynamic and kinetic mechanism of the polymorphic transformation of PUE, including the solvent-mediated polymorphic transformation (SMPT) of PUEMH to PUEDH and the solid-state polymorphic transformations (SSPTs) of PUEMH and PUEDH. PUEMH and PUEDH were identified as isolated and channel hydrate, respectively. The thermodynamic parameters (ΔG < 0, ΔH < 0, and ΔS < 0) indicated that the SMPT was a spontaneous, exothermic and entropy-decreased reaction. The facilitating roles of stirring rate and temperature on the SMPT were favored by the primary and secondary nucleation process of PUEDH. In addition, the results of SSPTs suggested that PUEMH and PUEDH would transform to two different anhydrates (PUEAH-I and PUEAH-II) upon heating, respectively. The dehydration rate of PUEMH was slower than that of PUEDH due to the stronger hydrogen bond interactions. The rate-limiting step for the dehydration of PUEMH was the diffusion of water molecules, resulting in the increased dehydration activation during the dehydration process, while the dehydration activation energy of PUEDH showed opposite trend due to the complicated crystallization process of PUEAH-II.

11.
Medicine (Baltimore) ; 100(4): e24455, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530254

RESUMO

RATIONALE: The clinical prognosis of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) patients is poor. Therefore, effective treatment is still a challenge at present. Moreover, little is known about the value of radiotherapy in the treatment of PTCL-NOS. PATIENT CONCERNS: A 55-year-old male patient with eating difficulties and progressive exacerbation for 3 months was diagnosed as non-Hodgkin's lymphoma. Airway compression occurred after 2 cycles of first line treatment with cyclophosphamide-Adriamycin-vincristine-prednisone regimen, radiotherapy (48Gy/24f) was given as the second line therapy. DIAGNOSIS: After radiotherapy, the patient complained that mild intermittent dysphagia still existed. Endoscopic biopsy of the upper digestive tract confirmed necrotic material and superficial squamous epithelial mucosa, suggesting esophageal stricture after radiotherapy, which was indistinguishable from tumor residue. INTERVENTIONS: The patient received anti-inflammatory treatment outside the hospital and did not receive any other special treatment. OUTCOMES: The symptoms of dysphagia disappeared and the focus showed complete response (CR). As of October 1, 2020, the patient has been diagnosed with PTCL-NOS for more than 57 months and the overall survival (OS) have not been achieved. LESSONS: Radiotherapy has obvious and rapid anti-tumor effect on cyclophosphamide-Adriamycin-vincristine-prednisone refractory PTCL-NOS. At the same time, hollow organs after radiotherapy can lead to lumen stenosis and the symptoms of suspected recurrence which is difficult to distinguish only from the imaging findings.


Assuntos
Esôfago/lesões , Linfoma de Células T Periférico/terapia , Radioterapia/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Afasia/etiologia , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Linfoma de Células T Periférico/diagnóstico por imagem , Linfoma de Células T Periférico/tratamento farmacológico , Linfoma de Células T Periférico/patologia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Prednisolona/uso terapêutico , Intervalo Livre de Progressão , Vincristina/uso terapêutico
13.
Inorg Chem ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33615779

RESUMO

Although many strategies have been used to help design effective near-infrared (NIR) luminescent materials, it is still a huge challenge to realize long-wavelength NIR luminescence of diimineplatinum(II) complexes in the solid state. Herein, we have successfully achieved long-wavelength NIR luminescence of a family of diimineplatinum(II) complexes based on a new strategy that combines a one-dimensional (1D) "Pt wire" structure with the electronic effect of the substituent. The structures of six solvated diimineplatinum(II) complexes based on 4,4-dichloro-2,2'-bipyridine or 4,4-dibromo-2,2'-bipyridine and 4-substituted phenylacetylene ligands have been determined, namely, 1·1/2toluene, 2·1/2THF, 3·1/8toluene, 4·1/2THF, 5·1/8CH2Cl2, and 6·1/4toluene. All of them crystallize in the monoclinic space group C2/c or C2/m and stack in the 1D "Pt wire" structure. In the solid state, six complexes exhibited unusual long-wavelength metal-metal-to-ligand charge-transfer luminescence that peaked at 984, 1044, 972, 990, 1022, and 935 nm, respectively. Interestingly, 2·1/2THF has the shortest Pt···Pt distance and the longest emission wavelength among the six complexes. As far as we know, the luminescence of 2·1/2THF at 1044 nm is the longest emission wavelength among known diimineplatinum(II) complexes. Systematic studies revealed that good molecular planarity, suitable substituent position, weak hydrogen-bond-forming ability of the substituents, appropriate molecular bending, and weakening of the interaction between solvated molecules and platinum molecules are conducive to the construction of a 1D "Pt wire" structure of the diimineplatinum(II) complex. Furthermore, the emission energy of the complex is mainly determined by the strength of the Pt-Pt interaction and electronic effect of the substituent.

14.
Oxid Med Cell Longev ; 2021: 9703682, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613827

RESUMO

Background: The liver is one of the most commonly affected organs in multiple organ dysfunction syndrome (MODS). In recent years, there have been many studies on Ganoderma lucidum polysaccharides (GLP), but the role of GLP in MODS is still unclear. The purpose of this work was to explore the antioxidant, anti-inflammatory, and protective effects of GLP on the liver in MODS model mice. Methods: The characteristic properties of GLP were processed by physicochemical analysis. The MODS models were successfully established with intraperitoneal injection of zymosan in Kunming strain mice. The antioxidant, anti-inflammatory, and hepatoprotective effects of GLP were processed both in vitro and in vivo by evaluating the oxidative parameters, inflammatory factors, and liver pathological observations. Results: The characterization analysis revealed that GLP was a pyranose mainly composed of glucose with the molecular weights (Mw) of 8309 Da. The experimental results proved that GLP had potential hepatoprotection possibly by improving the antioxidant status (scavenging excessive oxygen radicals, increasing the antioxidant enzyme activities, and reducing the lipid peroxide), alleviating the inflammatory response (reducing the inflammatory factor levels), and guaranteeing the liver functions. Conclusions: This research suggested that GLP had the potential to be developed as a natural medicine for the treatment of multiple organ failure.

15.
Transplantation ; 105(3): 569-576, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33617202

RESUMO

BACKGROUND: We evaluated the outcome of liver transplantation (LT) in neonatal-onset citrullinemia type I patients, especially its impact on neurological deficits and developmental retardation. METHODS: From October 2006 to October 2019, 5 of the 2003 children who received LT at Ren Ji Hospital had been diagnosed with citrullinemia type I. The primary indication for transplantation was repeated metabolic compensation and developmental retardation in 4 patients and prophylactic transplantation in the other. Among them, 3 patients received living donor LT and 2 received orthotopic LT. RESULTS: All recipients had successfully recovered within the median follow-up period of 32 months (range, 6-54 mo). Transplantation restored citrulline metabolism and liver function. Plasma ammonia and citrulline concentration decreased to normal levels with no further hyperammonemic episodes being reported, even after normal diet intake began. Meanwhile, uracil-2 and orotic acid were not detected in urinary excretion. Strikingly, patients suffered developmental retardation before LT showed improved psychomotor ability and significant catch-up growth during the follow-up period. Cognitive ability, including language skills and academic performance, also greatly improved. Three patients had sustained brain injuries and exhibited severe neurological deficits before transplantation, especially repeated generalized tonic-clonic seizures. LT halted neurological deterioration and controlled seizure episodes, which further facilitated the intellectual development and improvement of life quality. CONCLUSIONS: LT is an effective treatment for neonatal-onset citrullinemia type I patients, which reverses metabolism decompensation and improves quality of life. For patients who have suffered severe hyperammonemic insults, LT should be conducted at an early age to avoid further neurological or developmental deficits.

16.
Sci Rep ; 11(1): 3779, 2021 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-33580165

RESUMO

In less than 6 months, COVID-19 spread rapidly around the world and became a global health concern. Hypertension is the most common chronic disease in COVID-19 patients, but its impact on these patients has not been well described. In this retrospective study, 82 patients diagnosed with COVID-19 were enrolled, and epidemiological, demographic, clinical, laboratory, radiological and therapy-related data were analyzed and compared between COVID-19 patients with (29 cases) or without (53 cases) hypertension. The median age of the included patients was 60.5 years, and the cohort included 49 women (59.8%) and 33 (40.2%) men. Hypertension (31 [28.2%]) was the most common chronic illness, followed by diabetes (16 [19.5%]) and cardiovascular disease (15 [18.3%]). The most common symptoms were fatigue (55 [67.1%]), dry cough (46 [56.1%]) and fever ≥ 37.3 °C (46 [56.1%]). The median time from illness onset to positive RT-PCR test was 13.0 days (range 3-25 days). There were 6 deaths (20.7%) in the hypertension group and 5 deaths (9.4%) in the nonhypertension group, and more hypertensive patients with COVID-19 (8 [27.6%]) than nonhypertensive patients (2 [3.8%]) (P = 0.002) had at least one comorbid disease. Compared with nonhypertensive patients, hypertensive patients exhibited higher neutrophil counts, serum amyloid A, C-reactive protein, and NT-proBNP and lower lymphocyte counts and eGFR. Dynamic observations indicated more severe disease and poorer outcomes after hospital admission in the hypertension group. COVID-19 patients with hypertension have increased risks of severe inflammatory reactions, serious internal organ injury, and disease progression and deterioration.


Assuntos
/complicações , Hipertensão/epidemiologia , Insuficiência de Múltiplos Órgãos/epidemiologia , Idoso , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
17.
Int J Med Mushrooms ; 23(2): 85-96, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33639084

RESUMO

The present work was designed to investigate the antioxidant and hepatoprotective effects of acidic-hydrolysis Lentinus edodes residue polysaccharides (Ac-LRP) on lipopolysaccharide-induced liver injury in mice. Hepatoprotective effects were observed in liver treated with Ac-LRP at doses of 200, 400, and 600 mg/kg body weight, respectively. Activities of superoxide dismutase, glutathione peroxide, catalase, total antioxidant capacity, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase and levels of total cholesterol, triglyceride, malondialdehyde, and lipid peroxidation in liver or serum samples were analyzed. Ac-LRP reduced the incidence of liver necrosis detected via histological observations. In addition, Ac-LRP chemical bonds and ultrastructure were measured. These results provided valuable evidence supporting the utilization of Ac-LRP as a functional food and natural medicine for the treatment of liver injury.

18.
J Thorac Oncol ; 16(4): 583-600, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33388477

RESUMO

INTRODUCTION: Lung adenocarcinomas harboring EGFR mutations do not respond to immune checkpoint blockade therapy and their EGFR wildtype counterpart. The mechanisms underlying this lack of clinical response have been investigated but remain incompletely understood. METHODS: We analyzed three cohorts of resected lung adenocarcinomas (Profiling of Resistance Patterns of Oncogenic Signaling Pathways in Evaluation of Cancer of Thorax, Immune Genomic Profiling of NSCLC, and The Cancer Genome Atlas) and compared tumor immune microenvironment of EGFR-mutant tumors to EGFR wildtype tumors, to identify actionable regulators to target and potentially enhance the treatment response. RESULTS: EGFR-mutant NSCLC exhibited low programmed death-ligand 1, low tumor mutational burden, decreased number of cytotoxic T cells, and low T cell receptor clonality, consistent with an immune-inert phenotype, though T cell expansion ex vivo was preserved. In an analysis of 75 immune checkpoint genes, the top up-regulated genes in the EGFR-mutant tumors (NT5E and ADORA1) belonged to the CD73/adenosine pathway. Single-cell analysis revealed that the tumor cell population expressed CD73, both in the treatment-naive and resistant tumors. Using coculture systems with EGFR-mutant NSCLC cells, T regulatory cell proportion was decreased with CD73 knockdown. In an immune-competent mouse model of EGFR-mutant lung cancer, the CD73/adenosine pathway was markedly up-regulated and CD73 blockade significantly inhibited tumor growth. CONCLUSIONS: Our work revealed that EGFR-mutant NSCLC has an immune-inert phenotype. We identified the CD73/adenosine pathway as a potential therapeutic target for EGFR-mutant NSCLC.

19.
Br J Nutr ; : 1-9, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33494844

RESUMO

Experimental studies suggest that abnormal levels of Ca, Mg and phosphorus are implicated in pancreatic carcinogenesis. We investigated the associations between intakes of these minerals and the risk of pancreatic cancer in a case-control study conducted in 1994-1998. Cases of pancreatic cancer (n 150) were recruited from all hospitals in the metropolitan area of the Twin Cities and Mayo Clinic, Minnesota. Controls (n 459) were randomly selected from the general population and frequency matched to cases by age, sex and race. All dietary variables were adjusted for energy intake using the residual method prior to data analysis. Logistic regression was performed to evaluate the associations between intake of three nutrients examined and the risk of pancreatic cancer. Total intake of Ca (936 v. 1026 mg/d) and dietary intake of Mg (315 v. 331 mg/d) and phosphorus (1350 v. 1402 mg/d) were significantly lower in cases than in controls. After adjustment for confounders, there were not significant associations of total and dietary intakes of Ca, Mg and phosphorus with the risk of pancreatic cancer. In addition, no significant interactions exist between intakes of these minerals and total fat on pancreatic cancer risk. In conclusion, the present study does not suggest that intakes of Ca, Mg and phosphorus were significantly associated with the risk of pancreatic cancer.

20.
Biomed Pharmacother ; 135: 111004, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33433361

RESUMO

The present work was aimed to investigate the protective effects of enzymatic-hydrolyzed Auricularia polytricha polysaccharides (EnAPS) on renal functions. The characterizations were analyzed by physicochemical methods, and the renoprotections were processed in adenine-induced chronic kidney diseases (CKD) models of mice. Animal experiments exhibited that EnAPS showed superior renal-protections contributing to its antioxidant effects of increasing the enzyme activities and decreasing the lipid contents, and anti-inflammatory effects of reducing proinflammatory cytokines than A. polytricha polysaccharides (APS). Besides, the anti-apoptosis effects of EnAPS was proved by down-regulating Bax and Caspase-3 expressions and up-regulating Bcl-2 expressions by molecular biotechnology, and the anti-fibrosis effects was confirmed by histopathological observations of staining. The characterizations indicated that lower molecular weights possibly contributed to the superior renoprotective effects. These results suggested that enzymatic hydrolysis had potential effects in enhancing the bioactivities, and the polysaccharides could be used in the development of functional foods supplement against CKD.

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