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1.
J Nanosci Nanotechnol ; 20(4): 2267-2276, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492236

RESUMO

Two-dimensional (2D) BiOBr nanosheets (NSs) have attracted considerable interest as photocatalysts. The surface active sites of BiOBr NSs are crucial in determining the photocatalytic performance of these materials under visible light. The modification of the surface state of BiOBr NSs with multiple charged groups has been scarcely studied as a way to increase the number of surface active sites and the corresponding photocatalytic activity. Herein, vanadate-rich 2D BiOBr/Bi NSs were in-situ fabricated without adding strong reductants and subsequently used for visible-light-driven photocatalysis. Even under reductant-free condition, we were able to simultaneously deposit Bi0 and vanadate groups on the surface of pristine BiOBr NSs. The corresponding formation mechanism was also explored in a subsequent step. Compared to pristine BiOBr NSs and BiOBr/Bi NSs, the vanadate-rich BiOBr/Bi NSs prepared herein exhibited superior adsorption and enhanced photodegradation of Rhodamine B (RhB) under visible light illumination.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31713080

RESUMO

An obligately anaerobic, nitrate-reducing bacterial strain (MJB2T) was isolated from sediments of saline in Xinjiang province of China. Cells were Gram-stain-positive rods and motile by means of flagella and formed endospores. The novel strain MJB2T was able to grow at 15-37 °C (optimum 28-30 °C), pH 5.8-9.4 (optimum 7.8) and with 1.0-7.0% NaCl (optimum 5.0-6.0%, w/v). Sulfate, sulfite, thiosulfate, elemental sulfur, nitrite and Fe(III) were not used as terminal electron acceptors. Oxidase and catalase reactions were positive. H2S was producted from L-cystine. Complex substrates such as beef extract, peptone and yeast extract can be used as sole energy sources. The DNA G+C content was 29.4 mol%. The major cellular fatty acids (> 10%) were C14:0, C16:1 cis 7 and C16:1 cis 9. The main polar lipids consisted of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, three unidentified amino lipids, one unidentified amino glycolipid, two unidentified glycolipid, one unidentified aminophospholipid and two unidentified lipids. No respiratory quinones were detected. According to phylogenetic analysis based on 16S rRNA gene sequences, strain MJB2T was affiliated to the family Clostridiaceae (order Clostridiales) with highest 16S rRNA gene sequence similarity of 95.3% to Crassaminicella profunda Ra1766HT. Strain MJB2T exhibited 74.9% ANI values to C. profunda Ra1766HT. In silico DNA-DNA relatedness value between strain MJB2T and C. profunda Ra1766HT was 19.5%. The distinct biochemical, chemotaxonomic and phylogenetic differences from the previously described taxa supported that strain MJB2T represents a novel species of a new genus, for which the name Anaerophilus nitritogenes gen. nov., sp. nov. is proposed. The type strain is MJB2T (=KCTC 15800T=MCCC 1K03631T).

3.
Anal Chem ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31692331

RESUMO

In vivo detection of circulating tumor cells (CTCs) which inspect all of the circulating blood in body seems to have more advantages on cell capture, especially in earlier cancer diagnosis. Herein, based on in vivo microfluidic chip detection system (IV-chip-system), an extracorporeal circulation was constructed to effectively detect and monitor CTCs in vivo. Combined with microfluidic chip and immunomagnetic nanosphere (IMN), this system not only acts as a window for CTC monitoring but also serves as a collector for further cancer diagnosis and research on CTCs. Compared with the current in vivo detection method, this system can capture and detect CTCs in the bloodstream without any pretreatments, and it also has a higher CTC capture efficiency. It is worth mentioning that this system is stable and biocompatible without any irreversible damage to living animals. Taking use of this system, the mimicked CTC cleanup process in the blood vessel is monitored, which may open new insights in cancer research and early cancer diagnosis.

4.
J Econ Entomol ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31756251

RESUMO

Laodelphax striatellus (Fallén) is an important rice pest species which has developed high resistance to imidacloprid. Previous studies have demonstrated that CYP6AY3v2 and CYP353D1v2 were constitutively overexpressed in a imidacloprid resistant strain and can metabolize imidacloprid to mediated metabolic resistance. Further studies still needed to explore whether there are other L. striatellus P450 enzymes that can also metabolize imidacloprid. In this study, the expression level of L. striatellus CYP4C71 was significantly upregulated both in laboratory strains and field strains of L. striatellus after imidacloprid treatment for 4 h. The capability of CYP4C71 to metabolize imidacloprid was investigated. The full-length CYP4C71 was cloned, and its open reading frame was 1,515 bp with an enzyme estimated to be 505 amino acid residues in size. Furthermore, CYP4C71 was heterologously expressed along with L. striatellus cytochrome P450 reductase (CPR) in insect cells. A carbon monoxide difference spectra analysis confirmed the successful expression of CYP4C71. The recombinant CYP4C71 showed high P450 O-demethylation activity with PNP as a substrate. In vitro metabolism studies showed that recombinant CYP4C71 can metabolize imidacloprid to an easily excreted hydroxy-form. The rate of imidacloprid depletion in response to imidacloprid concentration revealed Michaelis Menten kinetics (R2 fitted curve = 0.99) with a relative low affinity: Kcat = 0.032 ± 0.009 pmol depleted imidacloprid/min/pmol P450 and Km=85.19 ± 2.93 µM. A relative big Km (85.19 ± 2.93 µM) indicated relative low imidacloprid's affinity for the CYP4C71 enzyme. In conclusion, CYP4C71 was another P450 enzyme that can metabolize imidacloprid with a relatively low affinity.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31757830

RESUMO

To produce high levels of ß-lactams, the filamentous fungus Penicillium rubens (previously named P. chrysogenum) has been subjected to an extensive classical strain improvement (CSI) program during the last few decades. This has led to the accumulation of many mutations that were statistically spread over the genome. Detailed analysis reveals that several mutations targeted genes that encode enzymes involved in amino acid metabolism, in particular L-cysteine biosynthesis, one of the amino acids used for ß-lactam production. To examine the impact of the mutations of the enzyme function, the respective genes with and without the mutations were cloned and expressed in E. coli, purified and enzymatically analyzed. Mutations severely impaired the activities of a threonine and serine deaminase, and this inactivates metabolic pathways that compete for L-cysteine biosynthesis. Tryptophan synthase, which converts L-serine into L-tryptophan, was inactivated by a mutation, whereas a mutation in the 5-aminolevulinate synthase, which utilizes glycine was without an effect. Importantly, the CSI caused increased expression levels of a set of genes directly involved in cysteine biosynthesis. These results suggest that the CSI has resulted in improved cysteine biosynthesis by inactivation of the enzymatic conversions that directly compete for resources with the cysteine biosynthetic pathway, consistent with the notion that cysteine is key component during penicillin production.IMPORTANCE Penicillium rubens is an important industrial producer of ß-lactam antibiotics. High levels of penicillin production were enforced through extensive mutagenesis during a classical strain improvement (CSI) program over 70 years. Several mutations targeted amino acid metabolism, and resulted in enhanced L-cysteine biosynthesis. This work provides a molecular explanation on the interrelation between secondary metabolite production and amino acid metabolism and how classical strain improvement has resulted in improved production strains.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31670869

RESUMO

Traditional photosensitizers (PSs) show reduced singlet oxygen (1 O2 ) production and quenched fluorescence upon aggregation in aqueous media, which greatly affect their efficiency in photodynamic therapy (PDT). Meanwhile, non-targeting PSs generally yield low efficiency in antibacterial performance due to their short lifetimes and small effective working radii. Herein, a water-dispersible membrane anchor (TBD-anchor) PS with aggregation-induced emission is designed and synthesized to generate 1 O2 on the bacterial membrane. TBD-anchor showed efficient antibacterial performance towards both Gram-negative (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). Over 99.8 % killing efficiency was obtained for methicillin-resistant S. aureus (MRSA) when they were exposed to 0.8 µm of TBD-anchor at a low white light dose (25 mW cm-2 ) for 10 minutes. TBD-anchor thus shows great promise as an effective antimicrobial agent to combat the menace of multidrug-resistant bacteria.

7.
Med Ultrason ; 21(4): 487-490, 2019 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-31765459

RESUMO

Primary hepatic carcinosarcoma (PHCS) is a very rare malignant tumor with a poor prognosis. Previous studies in the English-language literature were case reports, focused on the clinical aspects, pathology and pathogenesis. Much is unknownabout the imaging characteristics of PHCS while ultrasound is the first imaging examination for hepatic disease. Contrastenhancedultrasound (CEUS) is a proven method that improves the detection and characterization of focal liver lesions. The purpose of the paper is to present the ultrasonographic and other imaging appearance of three cases of PHCS.

8.
J Clin Invest ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31743111

RESUMO

A single sub-anesthetic dose of ketamine, an NMDA receptor (NMDAR) antagonist, produces rapid and sustained antidepressant actions in depressed patients, addressing a major unmet need for the treatment of mood disorders. Ketamine produces a rapid increase in extracellular glutamate and synaptic formation in the prefrontal cortex, but the initial cellular trigger that initiates these and its behavioral actions has not been identified. To address this question, we used a combination of viral shRNA and conditional mutation to produce cell specific knockdown or deletion of a key NMDAR subunit, GluN2B, implicated in the actions of ketamine. The results demonstrate that the antidepressant actions of ketamine were blocked by GluN2B-NMDAR knockdown on GABA (Gad1) interneurons, as well as subtypes expressing somatostatin (Sst), or parvalbumin (Pvalb), but not glutamate principle neurons in the mPFC. Further analysis of GABA subtypes showed that cell specific knockdown or deletion of GluN2B in Sst interneurons blocked or occluded the antidepressant actions of ketamine and revealed sex-specific differences that are associated with excitatory postsynaptic currents on mPFC principle neurons. These findings demonstrate that GluN2B-NMDARs on GABA interneurons are the initial cellular trigger for the rapid antidepressant actions of ketamine and show sex-specific adaptive mechanisms to GluN2B modulation.

9.
Int J Biol Macromol ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31739010

RESUMO

An open reading frame of sleh1, a gene encoding for a novel epoxide hydrolase from Solanum lycopersicum (SlEH1), was amplified by RT-PCR and expressed in E. coli BL21(DE3). The substrate spectrum assay showed that E. coli/sleh1 had EH activities towards all tested substrates except for racemic (rac-) 5a, and the highest enantiomeric ratio (E > 200) towards rac-2a, retaining (R)-2a with 99.1% ees and 49.2% yields and affording (R)-2b with 89.8% eep and 46.7% yieldp. Besides, E. coli/sleh1 also hydrolyzed of rac-7a-9a with moderate regioselectivities, producing (S)- or (R)-7b-9b with 40.5-51.3% eep and 69.4-75.2% yieldp. The pH optimum and stability of the purified SlEH1 were 7.5 and at a range of 6.5-8.5, and it was thermostable at or below 40 °C. Its catalytic efficiency (kcatS/KmS = 7.49 mM-1 s-1) for (S)-2a was much higher than that for (R)-2a. The gram-scale kinetic resolution of 150 mM rac-2a was carried out by E. coli/sleh1 at 20 °C for 8 h, producing (R)-2a with 98.2% ees and 45.3% overall yields after purification by silica gel column chromatography. Furthermore, the source of extremely high enantioselectivity of SlEH1 towards rac-2a was analyzed by molecular docking simulations.

10.
Microb Cell Fact ; 18(1): 202, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31739786

RESUMO

BACKGROUND: Epoxide hydrolase can regioselectively catalyze the oxirane ring-opening hydrolysis of rac-epoxides producing the corresponding chiral diols. In our laboratory, a gene named pveh1 encoding an EH from Phaseolus vulgaris was cloned. Although the directed modification of PvEH1 was carried out, the mutant PvEH1Y3 showed a limited degree of enantioconvergence towards racemic (rac-) m-chlorostyrene oxide (mCSO). RESULTS: PvEH1 and PvEH1Y3 were combinatively subjected to laboratory evolution to further enhance the enantioconvergence of PvEH1Y3 towards rac-mCSO. Firstly, the substrate-binding pocket of PvEH1 was identified using a CAVER 3.0 software, and divided into three zones. After all residues in zones 1 and 3 were subjected to leucine scanning, two E. coli transformants, E. coli/pveh1Y149L and /pveh1P184L, were selected, by which rac-mCSO was transformed into (R)-m-chlorophenyl-1,2-ethanediol (mCPED) having 55.1% and 27.2% eep. Secondly, two saturation mutagenesis libraries, E. coli/pveh1Y149X and /pveh1P184X (X: any one of 20 residues) were created at sites Y149 and P184 of PvEH1. Among all transformants, both E. coli/pveh1Y149L (65.8% αS and 55.1% eep) and /pveh1P184W (66.6% αS and 59.8% eep) possessed the highest enantioconvergences. Finally, the combinatorial mutagenesis was conducted by replacements of both Y149L and P184W in PvEH1Y3, constructing E. coli/pveh1Y3Z2, whose αS reached 97.5%, higher than that (75.3%) of E. coli/pveh1Y3. In addition, the enantioconvergent hydrolysis of 20 mM rac-mCSO was performed by E. coli/pveh1Y3Z2, giving (R)-mCPED with 95.2% eep and 97.2% yield. CONCLUSIONS: In summary, the enantioconvergence of PvEH1Y3Z2 was successfully improved by laboratory evolution, which was based on the study of substrate-binding pocket by leucine scanning. Our present work introduced an effective strategy for the directed modification of enantioconvergence of PvEH1.

11.
Colloids Surf B Biointerfaces ; : 110616, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31740323

RESUMO

Multidrug-resistant (MDR) bacterial strains have led to notable heathy threats to human beings. The demand for the development of effective antibacterial materials is increasing. Silver nanoparticles (AgNPs) and graphene-based nanomaterials are two major types of nanomaterials that are studied to inhibit and/or kill bacteria. In this study, by combining the excellent photothermal effect of graphene and antibacterial activity of AgNPs, we have applied reduced graphene oxide/silver (RGO/Ag) nanocomposite to destroy the MDR bacteria. The antibacterial activity of the RGO/Ag nanocomposite was systematically investigated using a regular bacterium of Escherichia coli (E. coli) and an MDR bacterium of Klebsiella pneumoniae (Kp). Compared with AgNPs, graphene oxide (GO) and RGO, the RGO/Ag nanocomposite showed significant higher antibacterial efficiency for both regular bacteria and MDR bacteria. Under a near-infrared (NIR) irradiation (0.30 W/cm2 for 10 min), the RGO/Ag nanocomposite demonstrated an enhanced synergetic antibacterial activity through the photothermal effect. Nearly 100 % of E. coli and Kp were killed by the treatment of 15 µg/mL and 30 µg/mL of RGO/Ag nanocomposite, respectively. Moreover, a membrane integrity assay and a reactive oxygen species (ROS) assay demonstrated that the RGO/Ag nanocomposite under NIR irradiation induced the cell membrane disruption and generation of ROS, providing possible mechanisms for their high antibacterial activity besides the photothermal effect. Finally, the cytotoxicity of the RGO/Ag nanocomposites toward different mammalian cells was studied, the cell viabilities retained above 60 % at higher concentrations of RGO/Ag, indicating that the RGO/Ag nanocomposites may be a low cytotoxic, efficient antibacterial agent with the irradiation.

12.
Neurobiol Dis ; 134: 104669, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31707118

RESUMO

Dysfunction of medial prefrontal cortex (mPFC) in association with imbalance of inhibitory and excitatory neurotransmission has been implicated in depression. However, the precise cellular mechanisms underlying this imbalance, particularly for GABAergic transmission in the mPFC, and the link with the rapid acting antidepressant ketamine remains poorly understood. Here we determined the influence of chronic unpredictable stress (CUS), an ethologically validated model of depression, on synaptic markers of GABA neurotransmission, and the influence of a single dose of ketamine on CUS-induced synaptic deficits in mPFC of male rodents. The results demonstrate that CUS decreases GABAergic proteins and the frequency of inhibitory post synaptic currents (IPSCs) of layer V mPFC pyramidal neurons, concomitant with depression-like behaviors. In contrast, a single dose of ketamine can reverse CUS-induced deficits of GABA markers, in conjunction with reversal of CUS-induced depressive-like behaviors. These findings provide further evidence of impairments of GABAergic synapses as key determinants of depressive behavior and highlight ketamine-induced synaptic responses that restore GABA inhibitory, as well as glutamate neurotransmission.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31600810

RESUMO

OBJECTIVE: The clinical data of patients with hemifacial spasm (HFS) were analyzed statistically to identify factors leading to delayed cure after microvascular decompression (MVD). METHODS: A retrospective analysis of the clinical data of 600 patients with HFS subjected to MVD from March 2016 to May 2018 was performed. Student t test, chi-square test, logistic regression analysis, and multivariate analysis of variance were used to analyze the correlation between delayed cure and its related factors. RESULTS: Among the 600 patients enrolled, 117 had delayed cure after MVD. The shortest duration of delayed cure was 4 days, and the longest was 540 days, with an average of 108 days. The frequency of delayed improvement in these patients was not associated with sex, age, or offending vessel type (p > 0.05); however, delayed cure was positively correlated with the course of the disease, grade of HFS severity, and disappearance of abnormal muscle responses during the operation (p < 0.05). Moreover, a longer disease course was associated with more severe related symptoms and a longer duration of postoperative delayed cure. CONCLUSION: MVD is an effective treatment for HFS. Given that postoperative delayed cure was unavoidable, even with accurate identification of the offending vessel and sufficient decompression of the root exit zone, delayed cure should be considered in patients undergoing reoperation due to lack of remission or relapse after the operation. Additionally, the timing of efficacy assessments should be delayed.

14.
J Cell Biol ; 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619485

RESUMO

The primary cilium is a sensory organelle that protrudes from the cell surface. Primary cilia undergo dynamic transitions between assembly and disassembly to exert their function in cell signaling. In this study, we identify the small GTPase Rab7 as a novel regulator of cilia disassembly. Depletion of Rab7 potently induced spontaneous ciliogenesis in proliferating cells and promoted cilia elongation during quiescence. Moreover, Rab7 performs an essential role in cilia disassembly; knockdown of Rab7 blocked serum-induced ciliary resorption, and active Rab7 was required for this process. Further, we demonstrate that Rab7 depletion significantly suppresses cilia tip excision, referred to as cilia ectocytosis, which has been identified as required for cilia disassembly. Mechanically, the failure of F-actin polymerization at the site of excision of cilia tips caused suppression of cilia ectocytosis on Rab7 depletion. Overall, our results suggest a novel function for Rab7 in regulating cilia ectocytosis and cilia disassembly via control of intraciliary F-actin polymerization.

16.
Diabetes Obes Metab ; 2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31588657

RESUMO

AIMS: To evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of rongliflozin in a cohort of healthy Chinese people and people with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: We examined the effects of a single ascending dose (SAD) of rongliflozin (10-200 mg) in combination with food (20 mg) in 50 healthy people, and a multiple ascending dose (MAD) of rongliflozin (10-50 mg once daily for 12 days) in 36 people with T2DM. RESULTS: No serious adverse events (AEs) or discontinuations as a result of AEs (related to rongliflozin) occurred in either study. In healthy participants and those with T2DM, rongliflozin was rapidly absorbed, with a time to maximum plasma concentration of 0.63 to 1.75 hours. Systemic exposure (maximum observed serum concentration and area under the curve) to rongliflozin and its inactive major metabolites (T1444, T1454 and T1830) increased in proportion to dose. In the SAD and MAD studies, there was a dose-related increase in urinary glucose excretion (UGE) ranging from 10 to 50 mg rongliflozin. This increase in UGE was associated with dose-related decreases in serum glucose values in people with T2DM in the MAD group. In the SAD group, UGE plateaued at 50 to 200 mg. CONCLUSIONS: Rongliflozin was well tolerated in all participants. The PK and PD measurements obtained for rongliflozin demonstrate a dose-response relationship when the drug is administered at doses ranging from 10 to 50 mg in healthy people and in people with T2DM.

17.
Cancer Imaging ; 19(1): 69, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31665093

RESUMO

OBJECTIVE: The present study aimed to evaluate the diagnostic performance and safety of PET/CT-guided percutaneous core bone biopsy and to compare the PET/CT-guided method to conventional CT-guided percutaneous core biopsies to diagnose Chinese patients with bone tumors and tumor-like lesions. METHODS: Data for 97 patients with bone tumors and tumor-like lesions diagnosed by percutaneous core bone biopsy from February 2013 to November 2018 were retrospectively analyzed. The study included 42 cases in the PET/CT group and 55 cases in the CT alone group. The diagnostic performance, cost and complications associated with the intervention were compared between the two groups. All patients were eventually confirmed to have bone tumors and tumor-like lesions according to surgical pathology findings. RESULTS: There were no significant differences in patient characteristics (P > 0.05). For the patients in the PET/CT group, the overall diagnostic yield of the initial biopsies and the diagnostic accuracy derived from the surgically proven cases were both 97.62%, which was significantly higher than the values in the CT group during the same period (P < 0.05). No major biopsy-related complications (e.g., serious bleeding or tumor dissemination) occurred before, during, or after the intervention. Therefore, no significant difference was observed between the two groups with regard to the complication rate (P > 0.05). CONCLUSION: Compared with CT-guided percutaneous bone biopsy, PET/CT-guided percutaneous bone biopsy is an effective and safe alternative with high diagnostic performance in the evaluation of hypermetabolic bone lesions to diagnose bone tumors and tumor-like lesions.

18.
Head Neck ; 41 Suppl 1: 19-45, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31573749

RESUMO

BACKGROUND: Biomarkers in head and neck squamous cell carcinoma (HNSCC) emerge rapidly in recent years, especially for new targeted therapies and immunotherapies. METHODS: Recent, relevant peer-reviewed evidence were critically reviewed and summarized. RESULTS: This review article briefly introduces essential biomarker concepts, including purposes and classifications (predictive, prognostic, and diagnostic markers), and the phases of biomarker development. We summarize current biomarkers in order of clinical utility; p16 and human papillomavirus status remain the most important and validated biomarkers in HNSCC. The rationale for biomarker study design continues to evolve with technological advances, especially whole-exome or whole-genomic sequencing. Noninvasive body fluid and liquid biopsy biomarkers appear to hold strong potential for development as tools for early cancer detection, cancer diagnosis, monitoring of disease recurrence, and outcome prediction. In light of discrepancies among different technologies, standardized approaches are needed. CONCLUSION: Biomarkers from cancer tissue or blood in HNSCC could direct new anticancer therapies.

19.
Cancer Lett ; 2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31639425

RESUMO

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) that links extracellular signals to the control of cell survival, growth, proliferation and differentiation. Due to its frequent overexpression and hyperactivation, EGFR has been a therapeutic target for human malignancies. Unfortunately, the specialized inhibitors of EGFR or EGFR-mediated pathways have not yet achieved the desired clinical effects. Therefore, it is necessary to elucidate the EGFR-mediated molecular basis of tumourigenesis, development and therapeutic resistance and to identify potential therapeutic targets. Interestingly, emerging research has indicated that autophagy is closely related to tumourigenesis, tumour progression and chemoresistance. Both autophagy upregulation and downregulation have been observed in cancers, suggesting its dual oncogenic and tumour suppressor properties during malignant transformation. Importantly, EGFR has been demonstrated to be a critical determinant of whether autophagy has a cytoprotective or cytotoxic effect. Therefore, here, we mainly focus on the function of EGFR in autophagy, especially the potential mechanism. The EGFR-mediated pathways or proteins involved in autophagy regulation include (1) the EGFR-mTOR pathway; (2) the EGFR-RAS pathway; (3) EGFR-Beclin1; (4) the EGFR-STAT3 pathway and (5) EGFR-LAPTM4B (oncoprotein lysosomal-associated transmembrane protein 4B). In addition, we also describe the role of EGFR-mediated autophagy in chemoresistance and tumour therapy. We attempt to summarized the mechanism by which EGFR-mediated signalling pathways participate in regulating autophagy and to investigate how to use the existing knowledge to identify potential cancer therapeutic targets.

20.
Haemophilia ; 2019 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-31657079

RESUMO

INTRODUCTION AND AIMS: Age-related severity and distribution of haemophilic arthropathy (HA) among Chinese patients with haemophilia using the Haemophilia Early Detection with Ultrasound (HEAD-US) system have not been extensively studied. METHODS: In our study, 89 patients with moderate and severe haemophilia were recruited. A total of 534 joints (knees, ankles and elbows on both sides included) were evaluated using musculoskeletal ultrasound (MSKUS) and scored using the HEAD-US system. RESULTS: Prevalence and average number of HA were 39.1% and 0.7, 90.6% and 3.2, 94.1% and 4.5, and 100% and 4.3 for ages ≤10, 11-20, 21-30 and 31-40 years, respectively. Prevalence and mean number of knee, ankle and elbow arthropathies also increased with age, although joint damages progressed in unparallel patterns. A significant difference in synovium subscores was observed between patients aged <10 and >10 years. An increasing tendency was observed in cartilage and subchondral bone subscores along with age before 30 years. No significant difference in mean joint scores was found between patients receiving on-demand therapy and those receiving on-demand to low-dose prophylactic therapy. CONCLUSIONS: Haemophilic arthropathy developed in early childhood and progressed mainly before 30 years of age among Chinese patients with haemophilia, although in different ways among the knee, ankle and elbow.

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