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1.
Molecules ; 26(21)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34770975

RESUMO

Acyclovir (ACV) is an effective and selective antiviral drug, and the study of its toxicology and the use of appropriate detection techniques to control its toxicity at safe levels are extremely important for medicine efforts and human health. This review discusses the mechanism driving ACV's ability to inhibit viral coding, starting from its development and pharmacology. A comprehensive summary of the existing preparation methods and synthetic materials, such as 5-aminoimidazole-4-carboxamide, guanine and its derivatives, and other purine derivatives, is presented to elucidate the preparation of ACV in detail. In addition, it presents valuable analytical procedures for the toxicological studies of ACV, which are essential for human use and dosing. Analytical methods, including spectrophotometry, high performance liquid chromatography (HPLC), liquid chromatography/tandem mass spectrometry (LC-MS/MS), electrochemical sensors, molecularly imprinted polymers (MIPs), and flow injection-chemiluminescence (FI-CL) are also highlighted. A brief description of the characteristics of each of these methods is also presented. Finally, insight is provided for the development of ACV to drive further innovation of ACV in pharmaceutical applications. This review provides a comprehensive summary of the past life and future challenges of ACV.

2.
Front Mol Neurosci ; 14: 720984, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34720871

RESUMO

Objective: The objective of this study is to explore the role of GRIN2A gene in idiopathic generalized epilepsies and the potential underlying mechanism for phenotypic variation. Methods: Whole-exome sequencing was performed in a cohort of 88 patients with idiopathic generalized epilepsies. Electro-physiological alterations of the recombinant N-methyl-D-aspartate receptors (NMDARs) containing GluN2A mutants were examined using two-electrode voltage-clamp recordings. The alterations of protein expression were detected by immunofluorescence staining and biotinylation. Previous studies reported that epilepsy related GRIN2A missense mutations were reviewed. The correlation among phenotypes, functional alterations, and molecular locations was analyzed. Results: Three novel heterozygous missense GRIN2A mutations (c.1770A > C/p.K590N, c.2636A > G/p.K879R, and c.3199C > T/p.R1067W) were identified in three unrelated cases. Electrophysiological analysis demonstrated R1067W significantly increased the current density of GluN1/GluN2A NMDARs. Immunofluorescence staining indicated GluN2A mutants had abundant distribution in the membrane and cytoplasm. Western blotting showed the ratios of surface and total expression of the three GluN2A-mutants were significantly increased comparing to the wild type. Further analysis on the reported missense mutations demonstrated that mutations with severe gain-of-function were associated with epileptic encephalopathy, while mutations with mild gain of function were associated with mild phenotypes, suggesting a quantitative correlation between gain-of-function and phenotypic severity. The mutations located around transmembrane domains were more frequently associated with severe phenotypes and absence seizure-related mutations were mostly located in carboxyl-terminal domain, suggesting molecular sub-regional effects. Significance: This study revealed GRIN2A gene was potentially a candidate pathogenic gene of idiopathic generalized epilepsies. The functional quantitative correlation and the molecular sub-regional implication of mutations helped in explaining the relatively mild clinical phenotypes and incomplete penetrance associated with GRIN2A variants.

3.
Immunotherapy ; 13(17): 1387-1393, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34665016

RESUMO

Hepatocellular carcinoma is one of the most common malignant tumors in China and is also a major cause of cancer deaths worldwide. Recent advances in immunotherapy have identified new treatments in which immunotherapy can be combined with antiangiogenic therapy. We report a case of hepatocellular carcinoma with a tumor thrombus at the inferior vena cava-right atrium junction and multiple lung metastases after a multiple-course treatment. Treatment with sintilimab in combination with sorafenib led to a partial remission and immune-related hepatitis.

4.
Appl Opt ; 60(23): 7036-7042, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34613187

RESUMO

A precise and fast optical thermometer based on a tunable diode laser absorption spectroscopy is developed for breath diagnostics with relevance to noncontact body temperature measurement. As water vapor (H2O) is the major component in human breath, two optimal absorption lines of H2O at 1392 nm and 1371 nm are selected for sensitive body temperature measurement by systematically investigating the near-infrared spectral database. The optical thermometer is developed using two distributed feedback diode lasers with the time-division multiplexing technique to achieve real-time measurement. The sensor performance such as accuracy, repeatability, and time response is tested in a custom-designed gas cell with its temperature controlled in the range of 20°C-50°C. By measuring the test air with different water concentrations, the sensor consistently shows a quadratic response to temperature with an R-squared value of 0.9998. Under the readout rate of 1 s, the sensor achieves a measurement precision of 0.16°C, suggesting its potential applications to fast, accurate, and noncontact body temperature measurements.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34633573

RESUMO

PURPOSES: Our study aimed to examine the impact of diabetes, smoking and BMI on pancreatic cancer survival in a population-based setting by adjusting both sociodemographic and clinical factors and measuring their attributable risk. METHODS: Data on pancreatic adenocarcinoma patients diagnosed in 2011-2017 were acquired from the Louisiana Tumor Registry. Diabetes, smoking, height, and weight were abstracted from medical records and linked with Hospital Inpatient Discharge Data to enhance the completeness of the diabetes data. The Cox regression model was used to assess effect sizes of diabetes, smoking, and BMI on cancer-specific survival and survival rate. The partial population attributable risk was employed to measure the attributable risk of these risk factors. RESULTS: Of the 3,200 eligible patients, 34.6% were diabetics, 23.9% were current smokers, and 52.3% had BMI ≥ 25 kg/m2. After adjusting for sociodemographic and clinical factors, diabetic patients had an increased cancer-specific death risk of 15% (95% CI, 1.06-1.25), 36% (95% CI, 1.19-1.44) for current smokers, and 24% (95% CI, 1.00-1.54) for patients with a BMI ≥ 40 when compared to their counterparts. Diabetic current smokers had significantly lower 2- and 3-year adjusted cancer-specific survival rates, 13.1% and 10.5%, respectively. By eliminating diabetes and modifiable risk factors, an estimated 16.6% (95% CI, 6.9%-25.9%) of the cancer-specific deaths could be avoided during a nine-year observational period between 2011 and 2019. CONCLUSIONS: Diabetes and smoking contributed substantially to the reduction of pancreatic cancer survival even after controlling for sociodemographic and clinical factors; however, BMI ≥ 35 was observed to increase risk of mortality among stage III-IV patients only.

6.
Nat Commun ; 12(1): 5919, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635651

RESUMO

Abnormal activation of epidermal growth factor receptor (EGFR) drives non-small cell lung cancer (NSCLC) development. EGFR mutations-mediated resistance to tyrosine-kinase inhibitors (TKIs) is a major hurdle for NSCLC treatment. Here, we show that F-box protein FBXL2 targets EGFR and EGFR TKI-resistant mutants for proteasome-mediated degradation, resulting in suppression of EGFR-driven NSCLC growth. Reduced FBXL2 expression is associated with poor clinical outcomes of NSCLC patients. Furthermore, we show that glucose-regulated protein 94 (Grp94) protects EGFR from degradation via blockage of FBXL2 binding to EGFR. Moreover, we have identified nebivolol, a clinically used small molecule inhibitor, that can upregulate FBXL2 expression to inhibit EGFR-driven NSCLC growth. Nebivolol in combination with osimertinib or Grp94-inhibitor-1 exhibits strong inhibitory effects on osimertinib-resistant NSCLC. Together, this study demonstrates that the FBXL2-Grp94-EGFR axis plays a critical role in NSCLC development and suggests that targeting FBXL2-Grp94 to destabilize EGFR may represent a putative therapeutic strategy for TKI-resistant NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas F-Box/genética , Neoplasias Pulmonares/genética , Glicoproteínas de Membrana/genética , Acrilamidas/farmacologia , Compostos de Anilina/farmacologia , Animais , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Sinergismo Farmacológico , Receptores ErbB/genética , Receptores ErbB/metabolismo , Proteínas F-Box/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Nus , Nebivolol/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais , Análise de Sobrevida , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Org Lett ; 23(21): 8147-8152, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34662133

RESUMO

With the aim of developing novel annulations via ketene intermediates, allenyl imide and alkynoates bearing good leaving groups are used for their function in a tandem conjugate addition-elimination reaction (SN2' type) promoted by nucleophilic phosphine catalysts. By utilizing thioamides as 1S,3N-bis-nucleophiles, [3+3] and [3+2] annulations have been established to allow rapid access to 1,3-thiazin-4-ones and 5-alkenyl thiazolones in high yields, respectively. Furthermore, the possible reaction mechanisms are proposed on the basis of deuterium labeling experiments and density functional theory calculations.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34702140

RESUMO

The conazole fungicide propiconazole is frequently found in vegetables although usage is not allowed. To overcome the high-cost and time-consuming labour requirements of instrumental methods, we developed a simple and visual lateral flow immunoassay for the sensitive determination of propiconazole. A hapten was carefully designed to raise a monoclonal antibody against propiconazole. Bal b/c mice were immunised with the hapten-carrier protein conjugate and a specific monoclonal antibody (mAb) was produced. Based on this mAb, a sensitive immunochromatographic strip assay (ICA) was established for rapid screening of propiconazole in vegetable samples. After optimisation of analytical parameters, the ICA strip showed a detection limit of 0.13 ng g-1 and a linear range from 0.5 to 80 ng g-1 using a strip reader. The assay also can be read by the naked eye with a visual limit of detection of 80 ng g-1. The recoveries for spiked vegetable samples by ICA ranged from 85.2% to 114.9%, with a coefficient of variation less than 11.7%. The assay time is within 45 min for a single sample including the sample pre-treatment. For spiked and blind samples, the detection capability of ICA was equivalent to liquid chromatography-mass spectrometry.

9.
Int J Infect Dis ; 113: 127-135, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34653656

RESUMO

OBJECTIVES: To investigate the risk of haematologic and solid organ malignancies in patients with haemorrhagic fever with renal syndrome (HFRS) compared with the general population. METHODS: This propensity-score-matched cohort study was conducted using data collected from the Korean national health insurance service (NHIS) between January 2003 and December 2017. The HFRS cohort included 5888 newly diagnosed cases of HFRS, and 412,804 general participants from the NHIS database were included as the control cohort. The incidence rate of malignancies was assessed and compared between the HFRS and control cohorts. RESULTS: There were 64 cases of haematologic malignancy in 236,286 person-years of observation, and 1245 cases of solid organ cancer in 209,333 person-years. The risks of haematologic malignancy and solid organ cancer were significantly higher in the HFRS cohort [adjusted hazards ratio (aHR) 4.10, 95% confidence interval (CI) 2.36-7.14] than the control cohort [aHR 2.97, 95% CI 2.60-3.38). In subgroup analysis, the HFRS cohort was associated with high hazard ratios for leukaemia and non-Hodgkin lymphoma. The HFRS cohort also had increased aHRs for all types of solid organ cancer. CONCLUSIONS: Patients with HFRS are at increased risk of both haematologic and solid organ malignancies compared with the general population, and this increased proportionally over time. Careful monitoring for malignancy after the onset of HFRS may be necessary.

10.
Environ Monit Assess ; 193(11): 720, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34643825

RESUMO

Long-term variation of nitrate in the East Sea was monitored in order to investigate impact of Three Gorges Dam (TGD) in the Changjiang River's upstream, China and Nakdong River's estuary dam, Korea. Tracing source of nitrate was another objective in this study. For this study, nutrient data were collected for 20 years from 1999 to 2018 in the East Sea, and divided into 4 sections, and evaluated whether a significant difference exists among the averages of nitrate concentrations. The concentrations of nitrate were affected by the major rivers (the Nakdong and the Taehwa Rivers) and Tsushima Warm Current (TWC) which diverged from the Kuroshio Current passing through East China Sea (ECS). Our results also indicated that long-term nitrate concentrations decreased and its reasons. First, the construction of TGD in the upstream of the Changjiang River may have resulted in the decrease of the nitrate supply in the river and ECS which is carried by TWC, toward the East Sea. Second, decrease in the nitrate flux of the Nakdong River's estuary due to the construction of the estuary dam and sewer treatment plant could also be a factor for the nitrate decrease in the East Sea. Therefore, anthropogenic activities from the Nakdong River and Changjiang River had a long-term effect on the East Sea's nitrate concentrations. The amount of nitrate runoff reduced by the anthropogenic activities influenced the nitrate levels over a long period by the flow of currents in the East Sea.


Assuntos
Monitoramento Ambiental , Nitratos , China , Estuários , Nitratos/análise , Oceanos e Mares , República da Coreia , Rios
11.
PLoS One ; 16(9): e0258113, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34591939

RESUMO

A numerical model of the dynamic triaxial test of graded crushed stone was established based on DEM (Discrete Element Method) to study its dynamic characteristics. The influence of test conditions on simulation results was analysed through numerical simulation. A method for determining the test conditions was proposed, and the reliability of the simulation was verified. We studied the accumulation rule and failure standard of permanent deformation. We then determined the critical failure stress level. The prediction model of permanent deformation cumulative failure was then established. When the calculation time step is greater than 1E-4 s per step, the stability of the dynamic triaxial numerical test of graded crushed stone is good. The plastic deformation of the simulated specimen tends to be stable under 10,000 dynamic loading cycles. When the specimen height and diameter are greater than 20 and 10 cm, respectively, the specimen size has little influence on the simulated axial strain. The recommended specimen size is 10 cm (Ф) × 20 cm (h). The action time curve results are consistent with indoor measurement results, which proves the simulation's reliability. The critical failure stress is approximately linearly correlated with the confining pressure, and the cumulative failure equation of plastic deformation is established.


Assuntos
Simulação por Computador , Modelos Teóricos , Estresse Mecânico , Humanos , Reprodutibilidade dos Testes
12.
Transl Vis Sci Technol ; 10(11): 14, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34520512

RESUMO

Purpose: Dry eye disease (DED) is a multifactorial disorder of the tears and ocular surface accompanied by ocular discomfort, visual disturbance, tear film instability, and ocular surface inflammation. In the present study, we evaluated the efficacy of the tyrosine kinase inhibitor imatinib mesylate for the treatment of DED. Methods: Experimental models of DED were generated in Sprague Dawley rats using a combination of benzalkonium chloride (BAC) with atropine sulfate and in New Zealand White rabbits using BAC. The animals were treated twice daily with eye drops of vehicle, imatinib (0.01%-0.3%), or a positive control (Restasis). The improvement in DED due to imatinib was assessed by staining with fluorescein, lissamine green, impression cytology, and histological analysis. In addition, immunofluorescence staining was performed at the end of the study to evaluate the inflammatory response in the ocular surface. Results: Topical application of imatinib significantly reduced ocular surface damage compared with vehicle-treated animals. Imatinib restored the morphology and structure of the conjunctival epithelium and reduced the recruitment of immune cells in the corneal epithelium. Furthermore, imatinib significantly reduced the impression cytology score, thus demonstrating that imatinib prevents the loss of goblet cells in DED animal models. The therapeutic efficacy of imatinib was similar to or better than that of cyclosporine treatment. Conclusions: In this study, we provide an animal in vivo proof of concept of the therapeutic potential of imatinib for the treatment of DED. Translational Relevance: With this study we show the possibility of developing imatinib as a new ophthalmic drop to treat DED.


Assuntos
Síndromes do Olho Seco , Epitélio Corneano , Animais , Síndromes do Olho Seco/induzido quimicamente , Mesilato de Imatinib , Modelos Animais , Inibidores de Proteínas Quinases/uso terapêutico , Coelhos , Ratos , Ratos Sprague-Dawley
13.
Biomaterials ; 277: 121061, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34508957

RESUMO

Patient-derived xenograft (PDX) models are powerful tools for understanding cancer biology and drug discovery. In this study, a polymeric nano-sized drug delivery system poly (OEGMA)-PTX@Ce6 (NPs@Ce6) composed of a photosensitizer chlorin e6 (Ce6) and a cathepsin B-sensitive polymer-paclitaxel (PTX) prodrug was constructed. The photochemical internalization (PCI) effect and enhanced chemo-photodynamic therapy (PDT) were achieved via a two-stage light irradiation strategy. The results showed that the NPs@Ce6 had great tumor targeting and rapid cellular uptake induced by PCI, thereby producing excellent anti-tumor effects on human bladder cancer PDX models with tumor growth inhibition greater than 98%. Bioinformatics analysis revealed that the combination of PTX chemotherapy and PDT up-regulated oxidative phosphorylation and reactive oxygen species (ROS) generation, blocked cell cycle and proliferation, and down-regulated the pathways related to tumor progression, invasion and metastasis, including hypoxia, TGF-ß signaling and TNF-α signaling pathways. Western blots analysis confirmed that proteins promoting apoptosis (Bax, Cleaved caspase-3, Cleaved PARP) and DNA damage (γH2A.X) were up-regulated, while those inhibiting apoptosis (Bcl-2) and mitosis (pan-actin and α/ß-tubulin) were down-regulated after chemo-PDT treatment. Therefore, this stimuli-responsive polymer-PTX prodrug-based nanomedicine with combinational chemotherapy and PDT evaluated in the PDX models could be a potential candidate for bladder cancer therapy.


Assuntos
Nanopartículas , Fotoquimioterapia , Porfirinas , Pró-Fármacos , Neoplasias da Bexiga Urinária , Linhagem Celular Tumoral , Xenoenxertos , Humanos , Fármacos Fotossensibilizantes , Neoplasias da Bexiga Urinária/tratamento farmacológico
14.
Am J Cancer Res ; 11(7): 3515-3536, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34354858

RESUMO

Gemcitabine is often recommended as a first-line treatment for patients with metastatic pancreatic cancer. However, gemcitabine resistance is a major challenge in the treatment of pancreatic ductal adenocarcinoma. Our group serendipitously identified the role of doxycycline as a potentiator of gemcitabine efficacy in pancreatic cancer cells. Doxycycline and gemcitabine co-treatment was significantly more cytotoxic to pancreatic cancer cells compared to gemcitabine alone. Interestingly, doxycycline only exerted synergistic effects when coupled with gemcitabine as opposed to other conventional chemotherapeutics including nucleoside analogs. The anti-clonogenic effects of gemcitabine on pancreatic cancer cells were also enhanced by doxycycline. According to cell cycle analyses, doxycycline prolonged gemcitabine-mediated S phase cell cycle arrest. Further, gene expression profiling analyses indicated that a small set of genes involved in cell cycle regulation were uniquely modulated by gemcitabine and doxycycline co-treatment compared to gemcitabine alone. Western blot analyses indicated that several cell cycle-related proteins, including cyclin D1, p21, and DNA damage inducible transcript 4 (DDIT4), were further modulated by doxycycline and gemcitabine co-treatment. Taken together, our findings indicate that doxycycline enhances the effects of gemcitabine on cell cycle progression, thus rendering pancreatic cancer cells more sensitive to gemcitabine. However, additional studies are required to assess the mechanisms of doxycycline and gemcitabine synergism, which might lead to novel treatment options for pancreatic cancer.

15.
Biology (Basel) ; 10(7)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203341

RESUMO

TGF-ß signaling plays a pivotal role in promoting tumor cell migration and cancer metastasis. ΔNp63α and TAp63α are two major isoforms of p53-related p63 protein. Our recent study has shown that TGF-ß1 promotes ΔNp63α protein degradation to facilitate cancer metastasis. However, whether TAp63α is involved in TGF-ß1-induced cancer metastasis remains unclear. In this study, we show that, in human pancreatic cancer MIA PaCa-2 cells harboring p53-R248W allele, TGF-ß1 can significantly inhibit TAp63α protein stability in a Smad pathway-independent manner. Lysosome inhibitor, chloroquine, but not proteasome inhibitor MG132, can rescue TGF-ß1-induced downregulation of TAp63α protein. In addition, we show that either TGF-ß1 treatment or silencing of TAp63α can dramatically increase migration of MIA PaCa-2 cells. Importantly, the restored expression of TAp63α can effectively block TGF-ß1-induced migration of MIA PaCa-2 cells. Mechanistically, we show that TGF-ß1 promotes TAp63α protein degradation, leading to upregulation of p53-R248W protein expression, and consequently resulting in elevated MIA PaCa-2 cell migration. Together, this study indicates that lysosomal degradation is an important way for regulating TAp63α protein fate and highlights that TGF-ß1-TAp63α-mutant p53 axis is critically important in pancreatic cancer metastasis.

16.
Materials (Basel) ; 14(13)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203216

RESUMO

Herein, the effects of the contents of emulsified asphalt, waterborne epoxy resin emulsion, and curing agent on the permeability, bond shear strength, water stability, and aging resistance of epoxy-emulsified asphalt were studied. A formulation of epoxy-emulsified asphalt as a fog-sealing adhesive material was recommended, and a comparison between the fabricated adhesive material and a traditional Chinese fog-sealing adhesive material was conducted to verify the technical performance of the new material. In addition, the strength formation mechanism of the epoxy-emulsified asphalt was revealed via microcosmic analysis. Results show that the curing agent content mainly affects the permeability of epoxy-emulsified asphalt, and the emulsified asphalt content significantly affects the bond shear strength, water stability, and aging resistance. Moreover, the ratio of waterborne epoxy resin emulsion to the curing agent (epoxy ratio) has a certain effect on the bond shear strength. In the recommended formulation (a high-permeability and high-bonding fog-sealing adhesive material, which can be referred to simply as HPBFA), emulsified asphalt accounts for 80% of the total mass of the mixture, and the epoxy ratio is 2:1-3:1. It can improve air permeability, bond shear strength, water stability and aging resistance. The HPBFA-cured material exhibits a continuous three-dimensional network structure, hydrophobic surface, and large contact angle. Furthermore, the initial thermal weight loss temperature of the HPBFA-cured material is significantly higher than the environmental aging temperature. Additionally, the maximum temperature decomposition range is 0-160 °C, indicating improved strength, wear resistance, permeability, and aging resistance of the material.

17.
Front Genet ; 12: 679097, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220951

RESUMO

Accumulating evidence has revealed that dysregulated lncRNA expression contributes to the onset and progression of cancer. However, the mechanistic role of lncRNA in glioma progression and tumor immunology remains largely unknown. This study aimed to evaluate the significance of maternally expressed gene 3 (MEG3) in the prognosis of and its immune-related roles in gliomas. The expression levels of MEG3 were analyzed using Oncomine and TIMER database. As an important imprinted gene, the copy number variation (CNV) of MEG3 in both glioblastoma multiforme (GBM) and low-grade glioma (LGG) were analyzed using GSCALite database, whereas its prognostic significance was assessed using PrognoScan and GEPIA databases. The relationship between MEG3 and tumor-infiltrated immune cells was analyzed using TIMER. Results showed that MEG3 expression was lower in most of the human cancer tissues than in the normal tissues. We also found that heterozygous deletion of MEG3 occurred more frequent than heterozygous amplification in gliomas, and mRNA expression of MEG3 was significantly positively correlated with its CNV in both the GBM and LGG group. Survival analysis showed that the CNV level of MEG3 had significant correlation with overall survival (OS) and progression-free survival (PFS) compared with wild type in LGG. Lower MEG3 expression was related with poor prognosis. Further analysis showed that in GBM, MEG3 expression level was significantly positively correlated with that of infiltrating CD8+ T cells and significantly negatively correlated with that of infiltrating dendritic cells. In LGG, MEG3 expression level was significantly negatively correlated with levels of infiltrating B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. Univariate Cox survival analysis demonstrated that only the level of infiltrating dendritic cells significantly affected the survival time of patients with GBM, while all six types of immune cells had a significant effect on the survival time of patients with LGG. Furthermore, MEG3 expression showed strong correlations with multiple immune markers in gliomas, especially in LGG. The current findings suggest that MEG3 expression might serve as a possible prognostic marker and potential immunotherapeutic target for gliomas.

18.
J Clin Transl Hepatol ; 9(3): 384-391, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34221924

RESUMO

Background and Aims: To investigate the usefulness of inflammation biomarkers to serve as a predictors of portal vein thrombosis (PVT) postoperatively (post) in patients with portal hypertension after splenectomy and periesophagogastric devascularization. Methods: A total of 177 liver cirrhosis patients were recruited from January 2013 to December 2017. They were divided into a PVT group (n=71) and a non-PVT group (n=106), according to ultrasound examination findings at 7-day post. Inflammation biomarkers involving platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), red blood cell distribution width-to-platelet ratio(RPR), mean platelet volume-to-platelet ratio (MPR) preoperatively (pre) and at 1, 3, 7-days post were recorded. Results: The univariate logistic regression analysis indicated that PLR (pre) (odds ratio (OR)=3.963, 95% confidence interval (CI)=2.070-7.587, p<0.000), MLR (pre) (OR=2.760, 95% CI=1.386-5.497, p=0.004), PLR (post-day 7) (OR=3.345, 95% CI=1.767-6.332, p=0.000) were significantly associated with the presence of PVT. The multivariate logistic regression analysis results indicated that PLR (pre) (OR=3.037, 95% CI=1.463-6.305, p=0.003), MLR (pre) (OR=2.188, 95% CI=1.003-4.772, p=0.049), PLR(post-day 7) (OR=2.166, 95% CI=1.053-4.454, p=0.036) were independent factors for predicting PVT. Conclusions: The PLR (pre), MLR (pre), and PLR (post-day 7) are predictors of portal vein thrombosis post in patients with portal hypertension after splenectomy and periesophagogastric devascularization.

19.
World J Clin Cases ; 9(19): 5082-5091, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34307559

RESUMO

BACKGROUND: Thallium poisoning is rare and difficult to recognize. Early diagnosis and treatment of thallium-poisoned patients are essential to prevent morbidity and mortality. AIM: To evaluate the efficacy of treatments and outcomes of five patients with early diagnosis of acute thallium poisoning. METHODS: Five patients who consumed a thallium-contaminated meal were hospitalized in succession, and underwent clinical examinations such as blood tests and electromyography tests. Urine and blood tests confirmed the diagnosis of thallotoxicosis, revealing the occurrence of food poisoning. All patients underwent detoxification treatment, including hemoperfusion (HP) and treatment with Prussian blue (PB). A 24-mo follow-up was performed to evaluate the long-term outcomes on the patients after discharge. RESULTS: Initially, the patients presented with symptoms of acute thallium poisoning including hyperalgesia of the limbs and abdominalgia, which may differ from common peripheral neuropathy. Accompanying symptoms such as hepatic damage and alopecia were observed in all the patients, which further confirmed the diagnosis of poisoning. Treatment with chelating agents was ineffective, while HP and treatment with PB drastically decreased the thallium concentration in the urine and blood. With early diagnosis and intervention, four patients had a good prognosis and no permanent sequelae. One patient developed blindness and disability during the 24-mo follow-up period. CONCLUSION: Identification of incident cluster and characteristic symptoms is extremely important for early diagnosis of acute thallium poisoning. HP plus PB is essential to improve the prognosis of thallium-poisoned patients.

20.
Pharmaceuticals (Basel) ; 14(6)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207383

RESUMO

Triple-negative breast cancer (TNBC) is a subset of breast cancer with aggressive characteristics and few therapeutic options. The lack of an appropriate therapeutic target is a challenging issue in treating TNBC. Although a high level expression of epidermal growth factor receptor (EGFR) has been associated with a poor prognosis among patients with TNBC, targeted anti-EGFR therapies have demonstrated limited efficacy for TNBC treatment in both clinical and preclinical settings. However, with the advantage of a number of clinically approved EGFR inhibitors (EGFRis), combination strategies have been explored as a promising approach to overcome the intrinsic resistance of TNBC to EGFRis. In this review, we analyzed the literature on the combination of EGFRis with other molecularly targeted therapeutics or conventional chemotherapeutics to understand the current knowledge and to provide potential therapeutic options for TNBC treatment.

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