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1.
Mol Cell Proteomics ; : 100051, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33549647

RESUMO

Sodium dodecyl sulfate (SDS) is widely used in sample preparation for proteomic research. However, SDS is incompatible with liquid chromatography and electrospray ionization (ESI). SDS depletion is therefore required ahead of liquid chromatography coupled with mass spectrometry (LC-MS) analysis. Most of current SDS removal strategies are time-consuming, laborious and have low reproducibility. Here, we describe a method, SDS-cyclodextrin assisted sample preparation (SCASP), by which cyclodextrin can bind to SDS and form cyclodextrins-SDS complexes in solutions, allowing for direct tryptic digestion. We demonstrate that SCASP is a simple, fast and robust SDS-based sample preparation method for proteomics application.

2.
J Magn Reson Imaging ; 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33555617

RESUMO

BACKGROUND: Gadolinium (Gd)-based contrast agents (GBCAs) have been widely used in MRI. However, several studies have reported Gd deposition in the brain, which has raised concerns about safety. PURPOSE: To investigate the effects of ischemic stroke on Gd deposition in the brain after repeated administration of linear or macrocyclic GBCAs and to determine whether GBCAs aggravate astrocyte injury after stroke. STUDY TYPE: Animal study. ANIMAL MODEL: Twenty-seven male Sprague-Dawley rats were randomized to an exposure group (n = 24) and a healthy control group (n = 3). Half of the exposure group (n = 12) underwent transient middle cerebral artery occlusion (tMCAO) and half (n = 12) had a sham procedure. In each subgroup (tMCAO or sham), the rats had repeated gadopentetate (n = 6) or gadobutrol (n = 6) injections. Oxygen-glucose deprivation and reoxygenation (OGD/R) was used as an in vitro model of stroke. ASSESSMENT: On day 3 and day 28 after the last injection (p.i.), the Gd concentration in the cerebrum was quantified by inductively coupled plasma mass spectrometry. Cell viability, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were analyzed in vitro. STATISTICAL TESTS: One-way analysis of variance and two-sample t-tests were performed. RESULTS: The Gd concentration in the ipsilateral hemisphere homogenates of tMCAO group was significantly higher than that in the brain homogenates of the sham group on day 3 p.i. of either gadobutrol (0.065 ± 0.006 vs. 0.042 ± 0.007 µg/g, P < 0.05) or gadopentetate (0.093 ± 0.010 vs. 0.069 ± 0.008 µg/g, P < 0.05). Increased Gd deposition was also found in the ipsilateral hemisphere homogenates of the tMCAO group compared with the brain homogenates of the sham group on day 28 p.i. of gadopentetate (0.075 ± 0.012 vs. 0.044 ± 0.003 µg/g, P < 0.05), but not gadobutrol (0.012 ± 0.007 vs. 0.010 ± 0.001 µg/g, P = 0.80). The Gd concentration in the ipsilateral hemisphere in the tMCAO group was significantly higher for gadopentetate than gadobutrol on both day 3 p.i. (0.085 ± 0.006 vs. 0.049 ± 0.005 µg/g, P < 0.05) and day 28 p.i (0.075 ± 0.012 vs. 0.012 ± 0.007 µg/g, P < 0.05). Additionally, compared with gadobutrol, gadopentetate decreased viability, increased ROS accumulation, and decreased MMP in OGD/R-induced astrocytes (all P < 0.05). DATA CONCLUSION: Administration of GBCAs after an animal model of ischemic stroke increased Gd deposition in the brain and aggravated astrocyte injury. The effect of gadopentetate appeared to be more pronounced than that of gadobutrol.

3.
Acta Radiol ; : 284185121990843, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33541090

RESUMO

BACKGROUND: Higher baseline Alberta Stroke Program Early Computed Tomography Score (ASPECTS) was associated with a lower probability of hemorrhagic transformation in patients with acute ischemic stroke (AIS). PURPOSE: To investigate the predictive value of cerebral blood volume (CBV)-ASPECTS of intracranial hemorrhage (ICH) in AIS treated with thrombectomy selected by computed tomographic perfusion (CTP) in an extended time window. MATERIAL AND METHODS: A total of 91 consecutive patients with AIS with large vessel occlusion in the anterior circulation after thrombectomy in an extended time window were enrolled between January 2018 and September 2019. ICH was diagnosed according to Heidelberg Bleeding Classification. CBV-ASPECTS was assessed by evaluating each ASPECTS region for relatively low CBV value compared with the mirror region in the contralateral hemisphere. Demographic characteristics, clinical data, CBV-ASPECTS, and procedure process and results were compared between patients with ICH and those without. RESULTS: ICH occurred in 31/91 (34.1%) patients with AIS. Symptomatic ICH (sICH) was observed in 4 (4.4%) patients, while asymptomatic ICH (aICH) was seen in 27 (29.7%). In univariate analysis, both ICH and aICH were associated with high admission NIHSS score (P<0.001 and P<0.001, respectively), more passes of retriever (P = 0.007 and P = 0.019, respectively), low NCCT-ASPECTS (P = 0.013 and P = 0.034, respectively), and low CBV-ASPECTS (P < 0.001 and P < 0.001, respectively). After multivariable analysis, low CBV-ASPECTS remained an independent predictor of ICH (odds ratio [OR] 0.521, 95% confidence interval [CI] 0.371-0.732, P < 0.001) and aICH (OR 0.532, 95% CI 0.376-0.752, P < 0.001), respectively. CONCLUSION: Low CBV-ASPECTS independently predicts ICH in patients with AIS treated with thrombectomy selected by CTP in an extended time window.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33543396

RESUMO

The development in nanobiotechnology provides an in-depth understanding of cell-surface interactions at the nanoscale level. Particularly, several surface features have shown the ability to interrogate the bacterial behavior and fate. In the past decade, the mechanical and physical sterilization has attracted considerable attention, as paradigms of such do not rely on chemical substances to damage or kill bacteria, whereas it is associated with natural living organisms or synthetic materials. Of note, such antibacterial scenario does not cause bacterial resistance, as the morphology of nanometer can directly cause bacterial death through physical and mechanical interactions. In this review, we provide an overview of recently developed technologies of leveraging topographical nanofeatures for physical sterilization. We mainly discuss the development of various morphologic nanostructures, and colloidal nanostructures show casing the capacity of "mechanical sterilization." Mechanically sterilized nanostructures can penetrate or cut through bacterial membranes. In addition, surface morphology, such as mechanical bactericidal nanoparticles and nanoneedles, can cause damage to the membrane of microorganisms, leading to cell lysis and death. Although the research in the field of mechanical sterilization is still in infancy, the effect of these nanostructure morphologies on sterilization has shown remarkable antibacterial potential, which could provide a new toolkit for anti-infection and antifouling applications. The mechanical and physical sterilization has attracted considerable attention, as paradigms of such do not rely on chemical substances to damage or kill bacteria. Moreover, such antibacterial scenario does not cause bacterial resistance, as the morphology of nanometer can directly cause bacterial death through physical and mechanical interactions. In this review, we focus on the advanced development of various morphologic nanostructures and colloidal nanostructures that show the capacity of "mechanical sterilization."

5.
Artigo em Inglês | MEDLINE | ID: mdl-33526298

RESUMO

INTRODUCTION: This study investigated the prevalence of and risk factors for alveolar fenestration and dehiscence in the anterior teeth of Chinese patients with skeletal Class III malocclusion. METHODS: This study included clinical and radiographic examinations and intraoperative observations of 460 anterior teeth from 54 patients who underwent corticotomy and periodontal regenerative surgery before orthodontic treatment. Fenestration and dehiscence were detected and recorded during open-flap surgery. Univariate and multivariate analyses were performed to assess relationships between fenestration and dehiscence and age, sex, history of previous orthodontic treatment, mandibular plane angle, dentition, tooth position, sagittal root position, periodontal biotype, gingival recession, width of keratinized gingiva, and width of the basal bone. RESULTS: The prevalence of buccal alveolar bone defects was 16.1% (fenestration) and 20.7% (dehiscence) at the tooth level. Multivariate logistic regressions showed that fenestration was significantly associated with tooth position (canine vs central incisor, odds ratio [OR] = 3.324; P = 0.006; lateral incisor vs central incisor, OR = 5.588; P  <0.001), and sagittal root position (buccally positioned vs centrally positioned, OR = 5.865; P = 0.025). Dehiscence was significantly associated with dentition (mandible vs maxilla, OR = 11.685; P  <0.001), tooth position (canine vs central incisor, OR = 3.863; P = 0.007), age (OR = 1.227; P = 0.010), sex (male vs female, OR = 5.530; P = 0.026), and history of orthodontic treatment (yes vs no, OR = 4.773; P = 0.028). CONCLUSIONS: Buccally positioned teeth in the osseous housing, lateral incisors, and canines were more likely to exhibit alveolar fenestration. Mandibular teeth and canines, patients who were older, were male, and had a history of orthodontic treatment, were more likely to exhibit alveolar dehiscence.

6.
Langmuir ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33529533

RESUMO

In transfer printing, the loaded droplet on the probe has a significant influence on the dispensing resolution. A suitable loading approach for a high-viscous liquid is highly required. Herein, a novel electrostatic loading method is presented, in which the main aim is to control precisely the formation and breaking of a cone-shaped liquid bridge. An experimental device is developed. The influence of electrical and geometric parameters on the feature size of the liquid bridge is investigated in detail. In the formation of the liquid bridge, the increase of voltage or the decrease of the air gap can enhance the electric field intensity, thus reducing the formation period and increasing the initial cone tip diameter of the liquid cone. After the liquid bridge is formed, both the circuit current implying the liquid wetted area on the probe surface and the lifting velocity of the probe are utilized to further regulate the volume of the loaded droplet. Loaded droplets ranging from 60 to 600 pL are obtained via the method with a standard deviation of 4 to 30 pL. Moreover, a dot array is transferred with different loaded droplets. The minimum diameter of the printed dots is about 140 µm with a variation less than 5%. The advantages include the reduced risk of contamination, the droplet-size independent of the size of the probe, and the low cost of the device.

8.
Med Care ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33560712

RESUMO

BACKGROUND: Breast cancer screening for women aged 40-49 years is prevalent and costly, with costs varying substantially across US regions. Newer approaches to mammography may improve cancer detection but also increase screening costs. We assessed factors associated with regional variation in screening costs. METHODS: We used Blue Cross Blue Shield Axis, a large US commercial claims database accessed through secure portal, to assess regional variation in screening utilization and costs. We included screening mammography±digital breast tomosynthesis (DBT), screening ultrasound, diagnostic mammography±DBT, diagnostic ultrasound, magnetic resonance imaging and biopsy, and evaluated their utilization and costs. We assessed regional variation in annual per-screened-beneficiary costs and examined potential savings from reducing regional variation. RESULTS: Of the 2,257,393 privately insured women, 41.2% received screening mammography in 2017 (range: 26.6%-54.2% across regions). Wide regional variation was found in the DBT proportion (0.7%-91.1%) and mean costs of DBT ($299; range: $113-714) and 2-dimensional (D) mammograms ($213; range: $107-471). In one-fourth of the regions, the mean DBT cost was lower than the mean 2D mammography cost in the full sample. Regional variation in the per-screened-beneficiary cost (mean: $353; range: $151-751) was mainly attributable to variation in the cost of DBT (accounting for 23.4% of regional variation) and 2D mammography (23.0%). Reducing regional variation by decreasing the highest values to the national mean was projected to save $79-335 million annually. CONCLUSIONS: The mean mammogram cost for privately insured women ages 40-49 varies 7-fold across regions, driving substantial variation in breast cancer screening costs. Reducing this regional variation would substantially decrease the screening costs.

9.
Acta Pharmacol Sin ; 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33574569

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with a minimal difference between its incidence rate and mortality rate. Advances in oncology over the past several decades have dramatically improved the overall survival of patients with multiple cancers due to the implementation of new techniques in early diagnosis, therapeutic drugs, and personalized therapy. However, pancreatic cancers remain recalcitrant, with a 5-year relative survival rate of <9%. The lack of measures for early diagnosis, strong resistance to chemotherapy, ineffective adjuvant chemotherapy and the unavailability of molecularly targeted therapy are responsible for the high mortality rate of this notorious disease. Genetically, PDAC progresses as a complex result of the activation of oncogenes and inactivation of tumor suppressors. Although next-generation sequencing has identified numerous new genetic alterations, their clinical implications remain unknown. Classically, oncogenic mutations in genes such as KRAS and loss-of-function mutations in tumor suppressors, such as TP53, CDNK2A, DPC4/SMAD4, and BRCA2, are frequently observed in PDAC. Currently, research on these key driver genes is still the main focus. Therefore, studies assessing the functions of these genes and their potential clinical implications are of paramount importance. In this review, we summarize the biological function of key driver genes and pharmaceutical targets in PDAC. In addition, we conclude the results of molecularly targeted therapies in clinical trials and discuss how to utilize these genetic alterations in further clinical practice.

10.
Sci Data ; 8(1): 54, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33547315

RESUMO

The 2019 coronavirus disease (COVID-19) is pseudonymously linked to more than 100 million cases in the world as of January 2021. High-quality data are needed but lacking in the understanding of and fighting against COVID-19. We provide a complete and updating hand-coded line-list dataset containing detailed information of the cases in China and outside the epicenter in Hubei province. The data are extracted from public disclosures by local health authorities, starting from January 19. This dataset contains a very rich set of features for the characterization of COVID-19's epidemiological properties, including individual cases' demographic information, travel history, potential virus exposure scenario, contacts with known infections, and timelines of symptom onset, quarantine, infection confirmation, and hospitalization. These cases can be considered the baseline COVID-19 transmissibility under extreme mitigation measures, and therefore, a reference for comparative scientific investigation and public policymaking.


Assuntos
/epidemiologia , /diagnóstico , China/epidemiologia , Busca de Comunicante , Demografia , Hospitalização , Humanos , Quarentena , Viagem
11.
Artigo em Inglês | MEDLINE | ID: mdl-33534601

RESUMO

Potyviruses move to neighboring cells in the form of virus particles or coat protein (CP)-containing ribonucleoprotein complex. However, the precise roles of RNA binding residues in potyviral CP in viral cell-to-cell movement remain to be elucidated. In this study, we predicted the three-dimensional model of tobacco vein banding mosaic potyvirus (TVBMV)-encoded CP and found nine residues presumably located in the CP RNA-binding pocket. Substitutions of the two basic residues at positions of 192 and 225 (R192 and K225) either with alanine, cysteine, or glutamic acid abolished TVBMV cell-to-cell and systemic movement in Nicotiana benthamiana plants. These substitutions also reduced the replication of the mutant viruses. Results from the electrophoretic mobility shift assay showed that the RNA binding activity of mutant CPs derived from R192 or K225 substitutions was significantly lower than that of wild-type CP. Analysis of purified virus particles showed that mutant viruses with R192 or K225 substitutions formed RNA-free virus-like particles. Mutations of R192 and K225 did not change the CP plasmodesmata localization. The wild-type TVBMV CP could rescue the deficient cell-to-cell movement of mutant viruses. Moreover, deletion of any of the other seven residues also abolished TVBMV cell-to-cell movement and reduced the CP-RNA binding activity. The corresponding nine residues in watermelon mosaic virus CP were also found to play essential roles in virus cell-to-cell movement. In conclusion, residues R192 and K225 in the CP RNA-binding pocket are critical for viral RNA binding and affect both virus replication and cell-to-cell movement.

12.
Signal Transduct Target Ther ; 6(1): 75, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33619259

RESUMO

The current treatment strategies in advanced malignancies remain limited. Notably, immunotherapies have raised hope for a successful control of these advanced diseases, but their therapeutic responses are suboptimal and vary considerably among individuals. Tumor-associated macrophages (TAMs) are a major component of the tumor microenvironment (TME) and are often correlated with poor prognosis and therapy resistance, including immunotherapies. Thus, a deeper understanding of the complex roles of TAMs in immunotherapy regulation could provide new insight into the TME. Furthermore, targeting of TAMs is an emerging field of interest due to the hope that these strategies will synergize with current immunotherapies. In this review, we summarize recent studies investigating the involvement of TAMs in immune checkpoint inhibition, tumor vaccines and adoptive cell transfer therapies, and discuss the therapeutic potential of targeting TAMs as an adjuvant therapy in tumor immunotherapies.

14.
Arch Gynecol Obstet ; 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33625596

RESUMO

PURPOSE: Vitamin D (VD) deficiency seems to be associated with the risk of recurrent spontaneous abortion (RSA). Vitamin D receptor (VDR) and cytochrome P450 family 2 subfamily R member 1 (CYP2R1) are two genes which are vital for VD metabolism and actions. However, whether single-nucleotide polymorphisms (SNPs) in these genes are correlated with the risk of RSA are poorly understood. Therefore, we aimed to characterize the relationships among VDR SNPs, CYP2R1 SNPs and RSA. METHODS: This case-control study enrolled 75 RSA patients and 83 controls. Serum VD and some cytokines were detected with LC-MS/MS and flow cytometry, respectively. Genotyping for three SNPs of CYP2R1 (rs10741657, rs10766197 and rs12794714) and five SNPs of VDR (rs7975232, rs1544410, rs2189480, rs2228570 and rs2239179) was done with polymerase chain reaction (PCR) and high-throughput sequencing. All the data were analyzed with appropriate methods and in different models. RESULTS: The results revealed a significant correlation between the AG genotype of CYP2R1 rs12794714 and VD levels (OR 0.686; 95% CI 0.49-0.96; p = 0.028). Besides, the AG and GG genotypes of CYP2R1 rs12794714 were markedly related to the risk of RSA (OR 52.394, 59.497; 95% CI 2.683-1023.265, 3.110-1138.367; p = 0.009, 0.007, respectively). CONCLUSION: Our results indicate that CYP2R1 rs12794714 might be a risk factor for RSA. Hence, early screening of pregnant women for CYP2R1 rs12794714 is necessary to warrant proactive counseling and treatment against RSA.

15.
Chemosphere ; 274: 129739, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33529949

RESUMO

To our knowledge, little evidence is available about effects of aircraft noise (AN), a non-chemical stressor, on cognitive function. Again, it is unknown whether or not the heat stress (HS)-induced cognitive deficits can be exacerbated by AN. The adult male mice were assigned to four groups: group 1 mice exposed to non-HS (24-26 °C 2 h daily for 4 consecutive days) and white noise (WN) (2 h daily for 4 consecutive days), group 2 mice exposed to WN and HS (32-34 °C 2 h daily for 4 consecutive days), group 3 mice exposed to AN and non-HS (2 h daily for 4 consecutive days) and group 4 mice exposed to AN and HS (2 h daily for consecutive 4 days). Cognitive function were determined by passive avoidance, Y-maze, Morris water maze, and novel object recognition tests. Gut barrier and blood-brain-barrier (BBB) permeability, upload of lipopolysaccharide (LPS) translocation, systemic and central inflammation, and stress reactions were examined. Heat stressed mice displayed both increased stress reactions and learning and memory loss. Heat stress also caused gut barrier hyperpermeability, increased upload of LPS translocation, systemic inflammation, BBB disruption and hippocampal neuroinflammation. Aircraft noise stressed mice did not display systemic inflammation but caused gut barrier hyperpermeability, increased upload of LPS translocation, increased stress reactions, BBB disruption, hippocampal neuroinflammation and cognitive deficits. Aircraft noise exposure further exacerbated the heat stress-induced cognitive deficits and its complications. Our data suggest that AN, like HS, causes cognitive impairments via similar mechanisms in male mice.

16.
Bioorg Chem ; 108: 104666, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33550070

RESUMO

Lysine-specific histone demethylase 1 (LSD1) was the first histone demethylase identified in epigenetics and has recently emerged as an attractive therapeutic target for treating tumors. To date, almost all reported LSD1 inhibitors have been chemosynthesized; however, natural products possess pharmacological and biological activity and can be sources for drug development. Here, we established a target separation countercurrent chromatography technique to isolate LSD1 inhibitors from zedoary turmeric oil. Four sesquiterpene-based LSD1 inhibitors were efficiently obtained with an inhibition ratio equal to or less than that of the positive control drug. Compound 2 showed the most potent inhibitory activity, with a half-maximal inhibitory concentration of 3.97 µM, and was further tested to determine its ability to inhibit LSD1 and its antitumor metastatic effects in MDA-MB-231 cells. These four compounds are the first sesquiterpene-based natural LSD1 inhibitors to be characterized. Our findings provide a new molecular framework for studying LSD1 inhibitors and offer a template for designing more sesquiterpene-based LSD1 inhibitors with potential antitumor activity.

17.
Ecotoxicol Environ Saf ; 208: 111705, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396036

RESUMO

The baking industries and disinfection of tap water released a considerable amount of bromate into surface water, which has been reported as a carcinogenic compound to mammals. Rotifers play an important role in freshwater ecosystems and are model organisms to assess environmental contamination. In the present study, the effects of different concentrations (0.001, 0.01, 0.1, 1, 10, 100 and 200 mg/L) of bromate on the life-table and population growth parameters were investigated in the rotifer Brachionus calyciflorus. The results showed that the 24-h LC50 of bromate to B. calyciflorus was 365.29 mg/L (95%Cl: 290.37-480.24). Treatments with 0.01, 10 and 200 mg/L bromate shorten the reproductive period. High levels of bromate (100 and 200 mg/L) significantly decreased net reproductive rate, intrinsic rate of population increase, life span, mictic rate of B. calyciflorus. To investigate the underlying mechanisms, swimming speed and antioxidative biomarkers were compared between bromate treatments and the control. The results showed that glutathione (GSH) and malondialdehyde (MDA) contents, total superoxide dismutase (T-SOD) and peroxidase (POD) activities decreased significantly in response to bromate exposure and the reasons required further investigation. Treatments with 0.001-200 mg/L bromate all significantly reduced swimming linear speed to rotifer larvae and treatments with 100-200 mg/L bromate significantly suppressed the swimming linear speed of adult rotifer. These changes would reduce filtration of algal food and could explain the decreased survival and reproduction. Overall, bromate may not show acute toxicity to rotifers, but still have potential adverse effects on rotifer behavior, which may then influence the community structure in aquatic ecosystems.


Assuntos
Bromatos/toxicidade , Rotíferos/efeitos dos fármacos , Rotíferos/fisiologia , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Bromatos/análise , Larva/efeitos dos fármacos , Larva/fisiologia , Crescimento Demográfico , Reprodução/efeitos dos fármacos , Rotíferos/crescimento & desenvolvimento , Rotíferos/metabolismo , Natação , Poluentes Químicos da Água/análise
18.
BMC Ophthalmol ; 21(1): 38, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446150

RESUMO

BACKGROUND: To analyze the clinical characteristics, treatment and prognosis of children with unilateral retinoblastoma (RB) and intracranial segment of retrobulbar optic nerve invasion. METHODS: A total of 14 children with unilateral RB and intracranial segment of retrobulbar optic nerve invasion were enrolled in this retrospective study from January 2009 to December 2018. Clinical characteristics, treatment and prognosis were collected and analyzed. Survival curves were calculated by Kaplan-Meier method. RESULTS: Of 14 cases, there were 7 male and 7 female, ranging in age from 22.85 to 121.97 months (median, 41.03 months). Seventy-one percent of patients came from first-tier cities in China and effected in the left eye. Magnetic resonance imaging (MRI) results indicated that all patients presented with thickened and enhanced optic nerve and intracranial segment of optic nerve invasion. Nine patients received comprehensive therapeutic regimen (chemotherapy, eye enucleation, radiotherapy and intrathecal therapy). The patients were followed up to December 2019, with a median follow-up of 20.6 months. The median disease specific survival was 48.99 ± 8.62 months, and the overall survival (OS) rate was 64.3%. Radiotherapy and comprehensive therapeutic regimen had significant impact on survival time (all p < 0.05). CONCLUSIONS: The overall prognosis of unilateral RB patients with intracranial segment of retrobulbar optic nerve invasion was poor. Chemotherapy and surgical treatment were necessary, but more attention should be paid to radiotherapy and intrathecal therapy for improving prognosis.

19.
ACS Sens ; 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33496573

RESUMO

Restriction endonucleases (ENases) and DNA methyltransferases (MTases) are important enzymes in biological processes, and detection of ENases/MTases activity is significant for biological and pharmaceutical studies. However, available nonamplification methods with a versatile design, desirable sensitivity, and signal production mode of unbiased quantification toward multiple nucleases are rare. By combining deliberately designed hairpin DNA probes with the colocalized particle counting technique, we present a nonamplification, separation-free method for multiplexed detection of ENases and MTases. In the presence of target ENases, the hairpin DNA is cleaved and the resulting DNA sequence forms a sandwich structure to tie two different-colored fluorescent microbeads together to generate a colocalization signal that can be easily detected using a standard fluorescence microscope. The multiplexed assay is realized via different color combinations. For the assay of methyltransferase, methylation by MTases prevents cleavage of the hairpin by the corresponding ENase, leading to decreased colocalization events. Three ENases can be simultaneously detected with high selectivity, minimal cross-talk, and detection limits of (4.1-6.4) × 10-4 U/mL, and the corresponding MTase activity can be measured without a change of the probe design. The potential for practical application is evaluated with human serum samples and different ENase and MTase inhibitors with satisfactory results. The proposed method is separation-free, unbiased toward multiple targets, and easy to implement, and the strategy has the potential to be extended to other targets.

20.
Nat Nanotechnol ; 16(1): 104-113, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33437035

RESUMO

Tumour heterogeneity remains a major challenge in cancer therapy owing to the different susceptibility of cells to chemotherapy within a solid tumour. Cancer stem-like cells (CSCs), which reside in hypoxic tumour regions, are characterized by high tumourigenicity and chemoresistance and are often responsible for tumour progression and recurrence. Here we report a nanotherapeutic strategy to kill CSCs in tumours using nanoparticles that are co-loaded with the differentiation-inducing agent, all-trans retinoic acid, and the chemotherapeutic drug, camptothecin. All-trans retinoic acid is released under hypoxic conditions, leading to CSC differentiation in the hypoxic niche. In differentiating CSC, the reactive oxygen species levels increase, which then causes the release of camptothecin and subsequent cell death. This dual strategy enables controlled drug release in CSCs and reduces stemness-related drug resistance, enhancing the chemotherapeutic response. In breast tumour mouse models, treatment with the nanoparticles suppresses tumour growth and prevents post-surgical tumour relapse and metastasis.

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