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1.
J Chromatogr A ; 1623: 461170, 2020 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-32505276

RESUMO

In this study, a multiresidue analytical method was developed, validated, and applied for quantifying 85 persistent organic pollutants (POPs), including 38 polychlorinated biphenyls (PCBs), 23 polybrominated diphenyl ethers (PBDEs), and 24 organochlorine pesticides (OCPs) from 200 µL of human serum. A modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) method was applied to minimize the required sample amount and optimize various conditions including the extraction solvent and the number of extractions. The extraction efficiency was optimized using double extraction with an ethyl acetate/hexane/acetone mixture. Gas chromatography coupled with triple-quadrupole mass spectrometry was used for analysis, and two different ionization sources, electron impact ionization (EI) and atmospheric pressure chemical ionization (APCI), were used to compare their sensitivity. The APCI source employed soft ionization at atmospheric pressure, producing abundant molecular ion formation with minimal fragmentation, in contrast to extensive fragmentation caused by EI. Of the 85 POPs analyzed, 59 target compounds (69.4%) showed lower limits of detection that were two- to fifty-fold lower in APCI than those determined using EI. The developed method was validated for its detection limit (0.5-10 pg/mL for PCBs, 2-20 pg/mL for PBDEs, and 2-40 pg/mL for OCPs), precision (0.8%-34.3% of coefficient of variation), recovery (49.6%-77.1%), matrix effect (46.7%-156.9%), and accuracy (81.2%-113.1% for PCBs, 85.8%-112.2% for PBDEs, and 55.2%-113.9% for OCPs). Its linearity was R2 > 0.99 for 84 compounds, and 96% average accuracy (for APCI) was obtained using the National Institute of Standards and Technology (NIST) standard reference materials (NIST 1957 and 1958). These ionization methods were compared by analyzing 25 real human serum samples. The observed species were 1.1-24.6 pg/mL of 28 PCBs, 2.5 pg/mL of BDE-47, and 6.5-195.1 pg/mL of 6 organochlorine pesticides (median concentration for each species), and only 11 compounds were detected with APCI owing to its enhanced sensitivity.

2.
J Chromatogr A ; 1623: 461210, 2020 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-32505294

RESUMO

Illegal dietary supplements adulterated with phosphodiesterase type 5 inhibitors (PDE-5i) are increasingly widely distributed through internet markets and underground routes. For this reason, it demands development of reliable screening methods to determine a wide range of PDE-5i drugs in various types of dietary supplements. Herein, we developed a screening method using gas chromatography-mass spectrometry (GC-MS) for simultaneous detection of 53 PDE-5i drugs in supplements. Common formulations (such as capsule, powder, pill, and tablet) of supplements with complicated matrices were treated by simple liquid-liquid extraction and trimethylsilyl (TMS) derivatization. With the aid of TMS derivatization, 53 PDE-5i drugs could be successfully separated and detected within 15 min, using a short microbore GC column (15 m). Moreover, owing to enhanced detection sensitivity and selectivity of PDE-5i TMS derivatives, 0.5 mg of sample was sufficient to screen and confirm targeted PDE-5i drugs. In this study, specific common ions according to structural characteristics of PDE-5i drugs were found under the electron ionization (EI) of their TMS derivatives. These specific common fragments could reflect the common pharmacophores for 4 classes of PDE-5i drugs (sildenafil, other sildenafil, vardenafil, and tadalafil analogues). Based on characteristic EI fragment ions, extracted common ion chromatograms (ECICs) and discriminant analysis (DA) were effectively used for reliable screening and classification of various types of PDE-5i drugs. Specific ECICs and DA using characteristic EI fragments here will aid in identification of newly emerging PDE-5i counterfeits in supplements. This study will be helpful to supervise illegal adulteration of PDE-5i drugs in dietary supplements to protect public health and consumer safety.

3.
Interv Neuroradiol ; : 1591019920931651, 2020 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-32524863

RESUMO

The perioperative optimal blood pressure targets during mechanical thrombectomy for acute ischemic stroke are uncertain, and randomized controlled trials addressing this issue are lacking. There is still no consensus on the optimal target for perioperative blood pressure in acute ischemic stroke patients with large vessel occlusion. In addition, there are many confounding factors that can influence the outcome including the patient's clinical history and stroke characteristics. We review the factors that have an impact on perioperative blood pressure change and discuss the influence of perioperative blood pressure on functional outcome after mechanical thrombectomy. In conclusion, we suggest that blood pressure should be carefully and flexibly managed perioperatively in patient-received mechanical thrombectomy. Blood pressure changes during mechanical thrombectomy were independently correlated with poor prognosis, and blood pressure should be maintained in a normal range perioperatively. Postoperative blood pressure control is associated with recanalization status in which successful recanalization requires normal range blood pressure (systolic blood pressure 120-140 mmHg), while non-recanalization requires higher blood pressure (systolic blood pressure 160-180 mmHg). The preoperative blood pressure targets for mechanical thrombectomy should be tailored based on the patient's clinical history (systolic blood pressure ≤185 mmHg). Blood pressure should be carefully and flexibly managed intraoperatively (systolic blood pressure 140-180 mmHg) in patient-received endovascular therapy.

4.
Clin Cardiol ; 2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32515510

RESUMO

BACKGROUND: Myocardial infarction in the absence of obstructive coronary artery disease (MINOCA) accounts for approximately 5% - 6% of acute myocardial infarction (AMI) patients. Anxiety symptoms are common in patients with coronary artery disease (CAD), and are associated with a poor prognosis. However, the association between anxiety and MINOCA outcomes is less clear. HYPOTHESIS: Anxiety will be associated with clinical outcomes in patients with MINOCA. METHODS AND RESULTS: Between November 2014 and December 2016, 620 hospitalized patients with MINOCA were recruited from a single center. Within 7 days of coronary angiography, anxiety was assessed using the Zung Self-Rating Anxiety Scale. The primary endpoint was all-cause mortality; secondary endpoint was any major adverse cardiovascular event (MACE). After 3 years, 87 deaths and 151 MACE had occurred. Kaplan-Meier curves indicated the unadjusted rates of all-cause mortality (log-rank P = .045) and MACE (log-rank P = .023) were significantly higher in the anxiety group compared with the control group of patients without anxiety. Multivariate Cox regression analysis showed that clinically significant anxiety was an independent prognostic factor for all-cause mortality as well as MACE (hazard ratio [HR] = 1.547; 95% confidence interval [CI], 1.006-2.380; P = .047; HR = 1.460; 95% CI, 1.049-2.031; P = .025; respectively). CONCLUSIONS: Anxiety is significantly and independently associated with an increased risk of all-cause mortality and MACE in patients with MINOCA.

5.
Cerebrovasc Dis ; : 1-7, 2020 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-32526736

RESUMO

BACKGROUND: Genetic variants may play a role in determining the location of cerebral atherosclerosis. We aimed to investigate the association between RNF213, MMP2, and genetic polymorphisms linked to vascular tortuosity with the location of cerebral arterial atherosclerosis. METHODS: A prospective case-control study was conducted on patients with ischemic stroke and age- and sex-matched stroke-free controls. The stroke patients were categorized into those with intracranial artery atherosclerosis (ICAS), extracranial artery atherosclerosis (ECAS), and small vessel occlusion (SVO). Six single nucleotide polymorphisms (SNPs) including rs2118181 (FBN1), rs2179357 (SLC2A10), rs1036095 (TGFBR2), rs243865 (MMP2), rs1800470 (TGFB1), and rs112735431 (RNF213) were analyzed with the TaqMan Genotyping Assay, and the distribution of genotypes across groups was compared. RESULTS: None of the 6 SNPs were associated with stroke on comparing the 449 stroke patients (71 with ECAS, 169 with ICAS, and 209 with SVO) to the 447 controls. In the subgroup analysis, the adjusted odds ratios (aORs) for age and sex indicated a significant association between rs112735431 and ICAS in the allele comparison analysis and in the additive and dominant model analyses. rs112735431 was associated with anterior circulation involvement and increased burden of cerebral atherosclerosis. rs2179357 was significantly associated with ICAS in the recessive model analysis, and rs1800470 was significantly associated with ECAS in the recessive model analysis when compared to controls. CONCLUSION: rs112735431 was associated with ICAS and increased atherosclerosis burden in Korean stroke patients. Further studies are needed to elucidate the role of rs112735431 and to confirm the association of rs2179357 and rs1800470 with cerebral atherosclerosis.

6.
Biomed Pharmacother ; 129: 110384, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32554248

RESUMO

A few clinical trials have recently reported the potential effect of colchicine in preventing post-operative atrial fibrillation (POAF) and early atrial fibrillation (AF) recurrence after catheter pulmonary vein isolation. However, the molecular mechanisms through which colchicine inhibits AF remain unclear. We aim to assess the anti-AF effect of colchicine in the rat sterile pericarditis (SP) model and to investigate its molecular mechanisms. SP was induced in Sprague-Dawley rats by the epicardial application of sterile talc. Treatment with colchicine or vehicle began 1 d before pericardiotomy. AF was induced by transesophageal burst pacing on day 3 after surgery. Treatment with colchicine reduced the duration of AF and the probability of induction of AF in SP rats. The dose of 0.5 mg kg-1·day-1 had the best effect. Such treatment also reduced neutrophil infiltration, the mRNA expression of IL-6, TGF-ß, and TNF-α, atrial fibrosis, fibrosis related genes, and signal molecules (STAT3, P38, and AKT). Meanwhile, the release of IL-1ß (4-24 h) and IL-6 (4-72 h) in atria after surgery was significantly inhibited by colchicine. In cultured rat cardiac fibroblasts, colchicine treatment inhibited IL-1ß-induced expression of IL-6, which was accompanied by significantly decreased phosphorylation of P38, AKT, JNK, and NFκB. Interestingly, the supplementation of IL-6 abolished the anti-AF effect of colchicine in SP rats. Colchicine prevents AF in SP rats through the inhibition of IL-1ß-induced IL-6 release and subsequent atrial fibrosis. However, further studies are required to investigate whether colchicine inhibits POAF through other mechanisms.

7.
Med Phys ; 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32542758

RESUMO

PURPOSE: High-Dose-Rate (HDR) brachytherapy is one of the most effective ways to treat the prostate cancer, which is the second most common cancer in men worldwide. This treatment delivers highly conformal dose through the transperineal needle implants and is guided by a real time ultrasound (US) imaging system. Currently, the brachytherapy needles in the US images are manually segmented by physicists during the treatment, which is time-consuming and error-prone. In this study, we propose a set of deep learning based algorithms to accurately segment the brachytherapy needles and locate the needle tips from the US images. METHODS: Two deep neural networks are developed to address this problem. First, a modified deep U-Net is used to segment the pixels belonging to the brachytherapy needles from the US images. Second, an additional VGG-16 based deep convolutional network is combined with the segmentation network to predict the locations of the needle tips. The networks are trained and evaluated on a clinical US images dataset with labeled needle trajectories collected in our hospital (Institutional Review Board approval (IRB 41755)). RESULTS: The evaluation results show that our method can accurately extract the trajectories of the needles with a resolution of 0.668 mm and 0.319 mm in x and y direction respectively. 95.4% of the x direction and 99.2% of the y direction have error ≤ 2 mm. Moreover, The position resolutions of the tips are 0.721 mm, 0.369 mm and 1.877 mm in x, y and z directions respectively, while 94.2%, 98.3% and 67.5% of the data have error ≤ 2 mm. CONCLUSIONS: This paper proposed a neural network based algorithm to segment the brachytherapy needles from the US images and locate the needle tip. It can be used in the HDR brachytherapy to help improve the efficiency and quality of the treatments.

8.
Cell ; 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32553274

RESUMO

Soybean is one of the most important vegetable oil and protein feed crops. To capture the entire genomic diversity, it is needed to construct a complete high-quality pan-genome from diverse soybean accessions. In this study, we performed individual de novo genome assemblies for 26 representative soybeans that were selected from 2,898 deeply sequenced accessions. Using these assembled genomes together with three previously reported genomes, we constructed a graph-based genome and performed pan-genome analysis, which identified numerous genetic variations that cannot be detected by direct mapping of short sequence reads onto a single reference genome. The structural variations from the 2,898 accessions that were genotyped based on the graph-based genome and the RNA sequencing (RNA-seq) data from the representative 26 accessions helped to link genetic variations to candidate genes that are responsible for important traits. This pan-genome resource will promote evolutionary and functional genomics studies in soybean.

9.
Dis Markers ; 2020: 2782101, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32566037

RESUMO

MicroRNAs play critical roles in tumor progression. Our recent study has indicated that microRNA-7 (miR-7) impairs autophagy-derived pools of glucose to suppress the glycolysis in pancreatic cancer progression. However, the roles of miR-7 in clinical significance and chemoresistance of pancreatic cancer remain unexplored. The aim of this study was to assess the expression of miR-7 in patients with pancreatic cancer and to evaluate the possibility of its usage as a prognostic molecular biomarker. MicroRNA array-based quantification analysis of 372 miRNAs was compared in serum between pancreatic cancer and healthy individuals, gemcitabine-sensitive and gemcitabine-resistance patients. We identified miR-7 showed the potential predictive power for gemcitabine-sensitive patients with pancreatic cancer. Then, the results were validated in pancreatic tissue microarray and The Cancer Genome Atlas (TCGA) dataset, demonstrating that lower miR-7 expression was correlated with more advanced tumor stages and worse prognosis in pancreatic cancer. The Cox proportional-hazards model analysis identified miR-7 to be an independent variable for prediction of the survival. Furthermore, the mechanistic exploration suggested the clinical significance of miR-7 involved its interference effect on autophagy and glycolysis in pancreatic cancer using pancreatic cancer tissue microarrays and TCGA data. Therefore, the results of the present study provide evidences that low microRNA-7 expression may contribute to tumor progression and poor prognosis in pancreatic cancer.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32588076

RESUMO

As ideal cells that can be used for adoptive cell therapy, γδ T cells are a group of homogeneous cells with high proliferative and tumor killing ability. However, γδ T cells are apt to apoptosis and show decreased cytotoxicity under persistent stimulation in vitro and cannot aggregate at tumor sites efficiently in vivo, both of which are two main obstacles to tumor adoptive immunotherapy. In this study, we found that the immune checkpoint T-cell immunoglobulin domain and mucin domain 3 (TIM-3) were up-regulated significantly on γδ T cells during their ex vivo expansion and this up-regulation contributed to the dysfunction of γδ T cells. Although the killing ability of γδ T cells against breast cancer cells which exhibited a high level of epithelial cell adhesion molecule (EpCAM) was enhanced, the level of TIM-3 on γδ T cells was also further up-regulated under the application of the bispecific antibody MT110 (anti-CD3 × anti-EpCAM) which can redirect T cells to target cells. Besides, these γδ T cells with up-regulated TIM-3 exhibited an increased susceptibility to apoptosis. By reinvigorating dysfunctional γδ T cells and promoting them to accumulate at tumor sites, the combined use of TIM-3 inhibitor and MT110 could further enhance the anti-tumor effect of the adoptively transfused γδ T cells. These results may have clinical implications for the design of new translational anti-tumor regimens aimed at combining checkpoint blockade and immune cell redirection.

12.
Medicine (Baltimore) ; 99(23): e20532, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32502010

RESUMO

BACKGROUND: JLC has been widely applied as a promising adjunctive drug for GC. However, the exact effects and safety of JLC have yet to be systematically investigated. We aimed to summarize the efficacy and safety of JLC for the treatment of advanced GC through the meta-analysis, in order to provide scientific reference for the design of future clinical trials. METHODS: The protocol followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. Relevant randomized controlled trials were searched from Cochrane Library, PubMed, Web of Science (WOS), Excerpt Medica Database (Embase), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), China Scientific Journal Database (VIP), and Wanfang Database. Papers in English or Chinese published from their inception to January 2020 will be included without any restrictions.Study selection and data extraction will be performed independently by 2 investigators. The clinical outcomes including overall response rate, complete response rate, overall survival, Disease-free survival, quality of life (QoL), immune function, and adverse events, were systematically evaluated. Review Manager 5.3 and Stata 14.0 were used for data analysis, and the quality of the studies was also evaluated. RESULTS AND CONCLUSION: The findings of this research will be published in a peer-reviewed journal, and provide more evidence-based guidance in clinical practice. INTERNATIONAL PLATFORM OF REGISTERED SYSTEMATIC REVIEW AND META-ANALYSIS PROTOCOLS (INPLASY) REGISTRATION NUMBER:: INPLASY202040105. URL: https://inplasy.com/inplasy-2020-4-0105/.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Intervalo Livre de Doença , Humanos , Metanálise como Assunto , Projetos de Pesquisa , Neoplasias Gástricas/mortalidade , Revisões Sistemáticas como Assunto
13.
J Patient Saf ; 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32398541

RESUMO

OBJECTIVE: We aimed to present neurological profiles and clinical outcomes of patients with acute neurological symptoms, which developed during hospitalization with nonneurological illness. METHODS: We organized the neurological alert team (NAT), a neurological rapid response team, to manage in-hospital neurological emergencies. In this registry-based study, we analyzed the clinical profiles and outcomes of patients who were consulted to the NAT. We also compared the 3-month mortality of patients with acute neurological symptoms with that of patients without acute neurological symptoms. RESULTS: Among the 85,507 adult patients, 591 (0.7%) activated the NAT. The most common reason for NAT activation was stroke symptoms (37.6%), followed by seizures (28.6%), and sudden unresponsiveness (24.0%). The most common diagnosis by the NAT neurologists was metabolic encephalopathy (45.5%), followed by ischemic stroke (21.2%) and seizures or status epilepticus (21.0%). Patients with NAT activation had high rates in mortality before hospital discharge (22.5%) and at 3 months (34.7%), transfer to intensive care units (39.6%), and length of hospital stay (43.1 ± 57.1 days). They also had high prevalence of poor functional status (78.1%) and recurrence of neurological symptoms at 3 months (27.2%). In a Cox proportional hazards model, patients with in-hospital neurological emergencies had a hazard ratio of 13.2 in terms of mortality at 3 months (95% confidence interval, 11.5-15.3; P < 0.001). CONCLUSIONS: Occurrence of acute neurological symptoms during hospital admission was associated with high rate of mortality and poor functional status. These results call for enhanced awareness and hospital-wide strategies for managing in-hospital neurological emergencies.

14.
Dalton Trans ; 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32369069

RESUMO

The Fenton reaction is regarded as an advanced oxidation process that can efficiently remediate environmental pollutants. However, the one-time irreversible consumption of its catalysts raises the cost in practical application. Herein, we report the generation of active Fe2+ sites via photo-reduction by photogenerated electrons on a TiO2 nanotube-based catalyst (TNT(Pd)/Fe2O3) with Fe2O3 decorated on the outside wall, while the inside cavity entrapped Pd nanoparticles. Fenton catalytic investigations under visible light show that TNT(Pd)/Fe2O3 displays superior methyl orange degradation activity with 90% removal in 10 minutes. The kinetic constant is 4.3 times as the sum of the pure photocatalysis and Fenton catalytic kinetic constants. The synergistic effect between the Fenton and photocatalytic reactions is further evidenced by the photocurrent and photodegradation tests. The TNT(Pd)/Fe2O3 catalyst showed no decay in the Fenton-photocatalytic performance over three successive cycles. XPS measurements after long-term stability tests revealed no loss, but a slight increase in the number of Fe2+ species. All of these results suggest that the most active Fe2+ species in the Fenton reaction can be regenerated via the reduction by photogenerated electrons. This work addressed the challenge in catalyst regeneration in the traditional Fenton reaction via photoreduction by rational combination with a photocatalyst and the realized synergistic effect between photocatalysis and the Fenton reaction.

15.
Environ Int ; 140: 105751, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32353668

RESUMO

Phthalate exposure was shown to alter thyroid function, however it is unclear, whether oxidative and nitrosative stress explains the intermediate biological mechanism. This study aimed to investigate the associations between phthalate exposure, oxidative/nitrosative stress, and thyroid function in adults, and to examine the mediating role of oxidative/nitrosative stress in the associations between phthalate exposure and thyroid function. Levels of eleven urinary phthalate metabolites, three urinary biomarkers of oxidative/nitrosative stress (malondialdehyde [MDA], 8-OHdG, and 8-NO2Gua) and five serum thyroid hormones (thyroxine [T4], free T4, triiodothyronine, thyroid-stimulating hormone, and thyroxine-binding globulin) were measured in 266 Taiwanese adults. Cross-sectional associations between phthalate metabolites, biomarkers of oxidative/ nitrosative stress and thyroid hormones were analyzed using multivariate regression models. Mediation analysis was conducted to assess the role of oxidative/nitrosative stress in the associations between phthalate metabolites and thyroid hormone levels. Sum of di-(2-ethylhexyl) phthalate (DEHP) metabolites was positively associated with MDA (ßT1-T2 = 0.253, 95%CI [0.060, 0.447]; ß â‰§ T2 = 0.317, 95% CI [0.098, 0.536]; Ptrend = 0.005) and 8-NO2Gua (ßT1-T2 = -0.010, 95%CI [-0.138, 0.118]; ß â‰§ T2 = 0.144, 95% CI [-0.001, 0.289]; Ptrend = 0.045). Mono-n-butyl phthalate (MnBP) was positively associated with 8-NO2Gua (ßT1-T2 = 0.201, 95% CI [0.078, -0.324]; ß â‰§ T2 = 0.161, 95% CI [0.031, -0.292]; Ptrend = 0.018). T4 was negatively associated with MDA (ßT1-T2 =  -0.027, 95% CI [-0.088, 0.0034]; ß≧T2 = -0.094, 95% CI [-0.161, -0.028]; Ptrend = 0.005) and 8-NO2Gua (ßT1-T2 = -0.068, 95% CI [-0.127, -0.010]; ß≧T2 = -0.125, 95% CI [-0.184, -0.066]; Ptrend < 0.001). Free T4 was positively associated with MDA (Ptrend = 0.047) and with 8-NO2Gua (Ptrend < 0.001). 8-NO2Gua mediated 11% of the association between the sum of DEHP metabolites and T4, and 17% of the association between MnBP and free T4. These results suggest that phthalate exposure may influence thyroid hormone levels through induced oxidative/nitrosative stress.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32357825

RESUMO

AIMS: The purpose of our study is to explore the combination effect of epirubicin and Bacillus Calmette Guerin (BCG) and its mechanism. BACKGROUND: Bladder cancer is a threat to human health worldwide. Commonly used chemotherapy drugs and biotherapy have significant therapeutic effects on bladder cancer, but the mechanism and combined effects are still unclear. OBJECTIVE: To evaluate the anti-cancer effect of epirubicin combined with BCG on human bladder cancer cells, our studies were carried out. METHODS: The viability of human bladder cancer cells with epirubicin and/or BCG treatments was examined by Cell Counting Kit-8 (CCK-8) assay. Apoptosis and cell cycle phase were determined by flow cytometry analysis. Pre-apoptosis factors of caspase-3, p53, B-cell lymphoma 2 associated X protein (Bax) and anti-apoptosis factor of B-cell lymphoma 2 (Bcl2) were detected by western blot. RESULTS: The viability of human bladder cancer with epirubicin or BCG treatment was decreased and the viability with epirubicin combined with BCG treatment was decreased more, which were determined by CCK-8 assay. Both epirubicin and BCG increased the apoptosis rate of human bladder cancer and arrested more cells into G0/G1 phase, which were tested by flow cytometry. The expression of caspase-3, p53 and Bax were increased and the expression of Bcl2 was decreased with epirubicin treatment on human bladder cells, which were analyzed by western blot. The expression of caspase-3 and p53 were increased with BCG treatment, which were examined by western blot. CONCLUSION: Epirubicin induced apoptosis in human bladder cancer cells by up-regulating the expression of pro-apoptotic factors (caspase-3, p53 and Bax) and down-regulating the expression of anti-apoptotic factor (Bcl-2). BCG promoted apoptosis of human bladder cancer cells by up-regulating the expression of caspase-3 and p53. BCG plays a potential role at the time of the combination of epirubicin and BCG on bladder cancer cells in early stage. Both epirubicin and BCG affected cell cycle distribution via arresting more bladder cancer cells at G0/G1 phase, which ultimately led bladder cancer proliferation in vitro and promoted apoptosis.

17.
Sci Rep ; 10(1): 7609, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32376878

RESUMO

Intraoperative neuromonitoring (IONM) facilitates recurrent laryngeal nerve (RLN) protection in thyroid and parathyroid surgeries. This study aimed to investigate a novel transcutaneous electromyography (EMG) recording method for IONM of the RLN during minimally invasive parathyroidectomy (MIP). Twenty patients with primary hyperparathyroidism undergoing MIP were enrolled. Two paired needle electrodes were percutaneously inserted into the bilateral laminas of thyroid cartilage for monitoring the vagus nerve and RLN. A standardized IONM procedure (V1-R1-R2-V2 signals) was strictly followed, and the RLN was routinely located and mapped. Pre- and postoperative laryngofiberoscopy was performed to confirm vocal cord function. The proposed technique was successfully used in all patients, and typical EMG signals were effectively detected. No significant change in EMG signals before and after tumor resection was noted, and a normal vocal cord movement was ensured in all patients with postoperative laryngofiberoscopy. IONM helped localize the position of the RLN and facilitated the safe resection of the parathyroid tumor during MIP. The novel transcutaneous EMG recording method proposed in this study was feasible, convenient, reliable, and inexpensive.

18.
J Am Chem Soc ; 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32362123

RESUMO

We report a novel solid-state molecular device structure based on double self-assembled monolayers (D-SAM) incorporated into the suspended nanowire architecture to form a "Au|SAM-1||SAM-2|Au" junction. Using commercially available thiol molecules that are devoid of synthetic difficulty, we constructed a "Au|S-(CH2)6-ferrocene||SAM-2|Au" junction with various lengths and chemical structures of SAM-2 to tune the coupling between the ferrocene conductive molecular orbital and electrode of the junction. Combining low noise and a wide temperature range measurement, we demonstrated systematically modulated conduction depending on the length and chemical nature of SAM-2. Meanwhile, the transport mechanism transition from tunneling to hopping and the intermediate state accompanied by the current fluctuation due to the coexistence of the hopping and tunneling transport channels were observed. Considering the versatility of this solid-state D-SAM in modulating the electrode-molecule interface and electroactive groups, this strategy thus provides a novel facile strategy for tailorable nanoscale charge transport studies and functional molecular devices.

19.
CNS Neurosci Ther ; 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32449258

RESUMO

INTRODUCTION: Astrogliosis and glial scar formation following spinal cord injury (SCI) are viewed as major obstacles that hinder axonal regeneration and functional recovery. Regulating the glial scar and axonal regeneration in the lesion site is important for treating SCI. AIMS: Considering the important role of astrocyte in glial scar formation and subsequent axonal regeneration, we intended to investigate the effect of the transcription factors OCT4 and KLF4 on astrocyte and the underlying mechanism after spinal cord contusion injury in transgenic mice. RESULTS: Western blotting, q-PCR, immunofluorescence, and functional evaluation suggested that glial fibrillary acidic protein (GFAP) expression decreased in the lesion area, the porosity of the scar increased, and remyelination enhanced. Mice overexpressing the transcription factors OCT4 and KLF4 had higher Basso Mouse Scale scores than did the control mice. Moreover, using immunofluorescence and Western blotting, we discovered that some astrocytes expressed nestin and sox2 protein, suggesting that these astrocytes were reprogrammed into neural stem cell-like cells. Furthermore, a cell scratch assay showed that the migration ability of the astrocytes was significantly inhibited in the presence of the transcription factors OCT4 and KLF4. In addition, we demonstrated that the Hippo/Yap pathway was activated after these two transcription factors overexpressed in astrocytes. CONCLUSIONS: In summary, these results suggest that overexpression of the transcription factors OCT4 and KLF4 could induce astrocyte reprogramming, which subsequently improves remyelination and functional recovery after SCI.

20.
Anal Chem ; 92(9): 6470-6477, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32249564

RESUMO

Nucleic acid aptamers have been widely used in various fields such as biosensing, DNA chip, and medical diagnosis. However, the high susceptibility of nucleic acids to ubiquitous nucleases reduces the biostability of aptamers and limits their applications in biological contexts. Therefore, improving the biostability of aptamers becomes an urgent need. Herein, we present a simple strategy to resolve this problem by directly replacing the d-DNA-based aptamers with left-handed l-DNA. By testing several reported aptamers against respective targets, we found that our proposed strategy stood up well for nonchiral small molecule targets (e.g., Hemin and cationic porphyrin) and chiral targets whose interactions with aptamers are chirality-independent (e.g., ATP). We also found that the l-DNA aptamers were indeed endowed with greatly improved biostability due to the extraordinary resistance of l-DNA to nuclease digestion. With respect to other small-molecule targets whose interactions with aptamers are chirality-dependent (e.g., kanamycin) and biomacromolecules (e.g., tyrosine kinase-7), however, the proposed strategy was not entirely effective likely due to the participation of the DNA backbone chirality into the target recognition. In spite of this limitation, this strategy indeed paves an easy way to screen highly biostable aptamers important for the applications in many fields.

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