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1.
Chin J Integr Med ; 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31705451

RESUMO

Resistance to anticancer drugs is a major problem in oncology, which causes the failure of antitumor treatment. A variety of factors contribute to drug resistance, including drug efflux and metabolism, tumor cell heterogeneity, tumor microenvironment stress-induced genetic or epigenetic alterations in the cancer cells and so on. However, how to circumvent this resistance to improve anticancer efficacy remains to be determined. To circumvent chemotherapeutic resistance, many reversal agents have been developed, but most of them fail in clinical trials due to severe adverse effects. Recently, several natural products have been reported to augment sensitivity or overcome resistance of anticancer chemotherapeutic drugs, including elemene, curcumin, Shenqi Fuzheng Injection (), PHY906, etc. Thus, understanding the novel function of Chinese medicine may allow us to develop a promising therapeutic approach to enhance the effects of anticancer strategies and prevent or overcome their resistance in the treatment of cancer patients.

2.
Int J Oncol ; 55(6): 1349-1360, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31638210

RESUMO

DNA replication is a vital process in cell division where anomalies can lead to tumorigenesis. Minichromosome maintenance complex component 10 (MCM10) plays a crucial role in this process. However, the role of MCM10 in lung cancer pathogenesis remains to be elucidated. In current study, using the publicly available lung cancer Gene Expression Omnibus (GEO) datasets, and Oncomine and the Cancer Genome Atlas databases, an increased expression of MCM10 was found in lung cancer tissues compared to normal lung tissues. The high expression of MCM10 was subsequently validated in clinical specimens by reverse transcription­quantitative PCR and immunohistochemistry. Analysis of the GEO datasets revealed that the high MCM10 expression was significantly associated with early and late recurrence, pathological stage and worse overall survival (OS). Cox's proportional hazards regression analyses revealed that MCM10 expression was an independent risk factor for poor OS and worse recurrence­free survival both in univariate and multivariate analysis. Furthermore, the increased expression of MCM10 was enriched in cell cycle­related processes, while in vitro transfection with small interfering RNA targeting MCM10 significantly suppressed cell viability, clone formation and induced G1 phase arrest in A549 and H661 cell lines by regulating the expression of cyclin D1 (CCND1). In addition, the current results indicated a combined effect of MCM10­CCND1 in predicting the prognosis of lung cancer patients. Altogether, the present study provided a novel potential molecular mechanism of lung cancer progression and may aid in development of novel treatment strategies.

3.
Medicine (Baltimore) ; 98(38): e17191, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567963

RESUMO

BACKGROUND: Primary dysmenorrhea (PD), the most common gynecological diseases, seriously affects women's life and work; however, without more effective treatment. Chinese herbal medicine (CHM) has been widely used for relieving dysmenorrheic pain in patients with PD. To assess the effectiveness and safety of CHM in patients with PD, a systematic review and meta-analysis of current published evidence regarding CHM as treatment for PD would be conducted in this study. METHODS: Literatures related to CHM for PD from the establishment of the database to June 2019 will be retrieved from the following databases: MEDLINE, EMBACE, Wed of Science and Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, and Wanfang Database. There are no language restrictions for retrieving literature. Eligible randomized clinical trials (RCTs) evaluating the effectiveness and safety of CHM in PD patients will be put in the study including outcomes of pain intensity, clinical effectiveness rate, quality of life, and adverse events. By scanning the titles, abstracts and full texts, 2 reviewers will independently select studies, extract data, and assess the quality of study. Meta-analysis of RCTs will be conducted using Review Manager 5.1 software. The results will be presented as risk ratio for dichotomous data, and standardized or weighted mean difference for continuous data. RESULT: This study will provide high-quality available evidence for the treatment of PD with CHM based on pain, clinical efficacy, quality of life, and adverse events. CONCLUSION: The systematic review willto evaluate the efficacy of CHM in treating PD and provide evidence for clinicians. PROSPERO REGISTRATION NUMBER: CRD42019121185.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Dismenorreia/tratamento farmacológico , Feminino , Humanos , Medicina Tradicional Chinesa/métodos , Resultado do Tratamento
4.
Parasit Vectors ; 12(1): 474, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31610804

RESUMO

BACKGROUND: The global spread of mosquito-borne diseases (MBD) has presented increasing challenges to public health. The transmission of MBD is mainly attributable to the biting behaviors of female mosquitoes. However, the ecological pattern of hourly host-seeking behavior in Aedes albopictus and its association with climatic variables are still not well understood, especially for a precise requirement for establishing an effective risk prediction system of MBD transmission. METHODS: Mosquito samples and data on mosquito hourly density and site-specific climatic variables, including temperature, relative humidity, illuminance and wind speed, were collected simultaneously in urban outdoor environments in Guangzhou during 2016-2018. Kernel regression models were used to assess the temporal patterns of hourly host-seeking behavior in mosquito populations, and negative binomial regression models in the Bayesian framework were used to investigate the associations of host-seeking behavior with climatic variables. RESULTS: Aedes albopictus was abundant, constituting 82% (5569/6790) of the total collected mosquitoes. Host-seeking behavior in Ae. albopictus varied across time and was significantly influenced by climatic variables. The predicted hourly mosquito densities showed non-linear relationships with temperature and illuminance, whereas density increased with relative humidity but generally decreased with wind speed. The range of temperature estimates for female biting was 16.4-37.1 °C, peaking at 26.5 °C (95% credible interval: 25.3-28.1). During the favorable periods, biting behavior of female Ae. albopictus was estimated to occur frequently all day long, presenting a bimodal distribution with peaks within 2-3 h around both dawn and dusk (05:00-08:00 h and 16:00-19:00 h). Moreover, a short-term association in hourly density between the females and males was found. CONCLUSIONS: Our field-based modeling study reveals that hourly host-seeking behavior of Ae. albopictus exhibits a complex pattern, with hourly variation constrained significantly by climatic variables. These findings lay a foundation for improving MBD risk assessments as well as practical strategies for vector control. For instances of all-day-long frequent female biting during the favorable periods in Guangzhou, effective integrated mosquito control measures must be taken throughout the day and night.

5.
Sci Rep ; 9(1): 14388, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31591428

RESUMO

We compared coastal restoration projects in a developing country, China, and a developed country, the United States of America, both of which are facing loss and degradation of coastal habitats at similar latitudes, for the period of 1992-2014. To document the scale of coastal habitat restoration projects in the two countries, we identified 914 coastal restoration projects with an accumulated area of 300,521 acres in China, with most of our information coming from scientific papers, and 1,620 coastal restoration projects with an accumulated area of 243,064 acres in the USA, with most of our information coming from public databases. In both countries, about half the projects were in wetland habitats, but China had a greater proportion of projects in submerged habitats (43% versus 28% in the USA) and the USA a greater proportion in coastal upland habitats (21% versus 9% in China). The number of new projects steadily increased over time in China, but dropped after 2006 in the USA, although the total cost of new projects continued to increase. The number of projects in China and the total cost of projects in the USA were correlated with national GDP. Restoration projects in China used fewer techniques, had fewer partners, and took longer to complete than projects in the USA. Information about projects was incomplete, especially in China, and both countries could do more to make information publically available. We know more about project construction than project outcomes, and it is unclear whether projects are achieving their goals or whether the techniques used are optimal.

6.
PLoS Negl Trop Dis ; 13(10): e0007391, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31618203

RESUMO

BACKGROUND: Myiasis due to Old World screw-worm fly, Chrysomya bezziana, is an important obligate zoonotic disease in the OIE-list of diseases and is found throughout much of Africa, the Indian subcontinent, southeast and east Asia. C. bezziana myiasis causes not only morbidity and death to animals and humans, but also economic losses in the livestock industries. Because of the aggressive and destructive nature of this disease in hosts, we initiated this study to provide a comprehensive understanding of human myiasis caused by C. bezziana. METHODS: We searched the databases in English (PubMed, Embase and African Index Medicus) and Chinese (CNKI, Wanfang, and Duxiu), and international government online reports to 6th February, 2019, to identify studies concerning C. bezziana. Another ten human cases in China and Papua New Guinea that our team had recorded were also included. RESULTS: We retrieved 1,048 reports from which 202 studies were ultimately eligible for inclusion in the present descriptive analyses. Since the first human case due to C. bezziana was reported in 1909, we have summarized 291 cases and found that these cases often occurred in patients with poor hygiene, low socio-economic conditions, old age, and underlying diseases including infections, age-related diseases, and noninfectious chronic diseases. But C. bezziana myiasis appears largely neglected as a serious medical or veterinary condition, with human and animal cases only reported in 16 and 24 countries respectively, despite this fly species being recorded in 44 countries worldwide. CONCLUSION: Our findings indicate that cryptic myiasis cases due to the obligate parasite, C. bezziana, are under-recognized. Through this study on C. bezziana etiology, clinical features, diagnosis, treatment, epidemiology, prevention and control, we call for more vigilance and awareness of the disease from governments, health authorities, clinicians, veterinary workers, nursing homes, and also the general public.

7.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 33(10): 1276-1282, 2019 Oct 15.
Artigo em Chinês | MEDLINE | ID: mdl-31544439

RESUMO

Objective: To observe the clinical application of multidisciplinary team (MDT) treatment in the management of geriatric hip fractures and evaluate its effectiveness. Methods: The clinical data of 76 elderly patients with hip fracture managed by MDT approach between August 2016 and February 2018 (MDT group) were retrospectively analyzed and compared with 102 patients managed by traditional orthopedics approach between January 2014 and December 2015 (conventional group). There was no significant difference in gender, age, fracture type, surgical procedure, and other general data between the two groups ( P>0.05). However, the number of comorbidities in the MDT group was significantly higher than that in the conventional group ( t=6.295, P=0.000), and the proportion of the number of comorbidities between the two groups was also significantly different ( χ 2=28.442, P=0.000). The consultation rate and transfer rate, time to surgery, rate of surgery within 2 or 3 days, operation time, postoperative hospitalization stay, length of hospitalization stay, hospitalization expense, rate of loss to follow-up, and mortality during hospitalization, 30-day mortality, 90-day mortality, and 1-year mortality after operation were compared between the two groups. Results: The rates of total consultations of the conventional group and the MDT group were 56.86% (58/102) and 56.58% (43/76), respectively, and the rates of total transferred patients were 15.69% (16/102) and 15.79% (12/76), respectively, with no significant differences ( P>0.05). Among them, the proportion of patients who transferred into intensive care unit (ICU) in conventional group was significantly higher than that in MDT group and the rates of patients who received geriatric consultation or transferred into geriatric department in MDT group were both significantly higher than those in conventional group ( P<0.05). There was no significant difference in rates of other department consultation or transfer between the two groups ( P>0.05). The time to surgery, operation time, postoperative hospitalization stay, and length of hospitalization stay in MDT group were significantly less than those in conventional group, but the proportion of patients who received surgery within 3 days in MDT group was significantly higher than that in conventional group ( P<0.05). There was no significant difference in the proportion of patients who received surgery within 2 days ( χ 2=2.027, P=0.155). The hospitalization expenses of total patients, femoral neck fracture, and intertrochanteric fracture subgroups in MDT group were all significantly higher than those in conventional group ( P<0.05). However, there was no significant difference in hospitalization expense of subtrochanteric fracture subgroup between the two groups ( Z=-1.715, P=0.086). The rate of loss to follow-up in conventional group and MDT group was 6.86% (7/102) and 3.95% (3/76), respectively, with no significant difference ( χ 2=0.698, P=0.403). The mortalities at hospitalization, 1 month, 3 months, and 1 year after operation in conventional group were 0, 1.05% (1/95), 3.16% (3/95), and 7.37% (7/95), respectively, and in MDT group were 0, 0, 2.74% (2/73), 6.85% (5/73), respectively, showing no significant differences in mortalities between the two groups ( P>0.05). Conclusion: MDT model in the management of geriatric hip fractures has been shown to reduce time to surgery, postoperative hospitalization stay, length of hospitalization stay, operation time, and the proportion of patients who received ICU consultation or transferred into ICU. Furthermore, MDT can improve the capacity for developing operations for patients with complex medical conditions and make medical resources used more rationally.


Assuntos
Fraturas do Colo Femoral , Fraturas do Quadril , Equipe de Assistência ao Paciente , Idoso , Humanos , Estudos Retrospectivos , Resultado do Tratamento
8.
Brief Bioinform ; 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31504150

RESUMO

Functional annotation of protein sequence with high accuracy has become one of the most important issues in modern biomedical studies, and computational approaches of significantly accelerated analysis process and enhanced accuracy are greatly desired. Although a variety of methods have been developed to elevate protein annotation accuracy, their ability in controlling false annotation rates remains either limited or not systematically evaluated. In this study, a protein encoding strategy, together with a deep learning algorithm, was proposed to control the false discovery rate in protein function annotation, and its performances were systematically compared with that of the traditional similarity-based and de novo approaches. Based on a comprehensive assessment from multiple perspectives, the proposed strategy and algorithm were found to perform better in both prediction stability and annotation accuracy compared with other de novo methods. Moreover, an in-depth assessment revealed that it possessed an improved capacity of controlling the false discovery rate compared with traditional methods. All in all, this study not only provided a comprehensive analysis on the performances of the newly proposed strategy but also provided a tool for the researcher in the fields of protein function annotation.

9.
Neurosci Res ; 2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31526851

RESUMO

We aimed to demonstrate the effects of microRNA (miR)-101 on neuropathic pain and explore the underlying mechanisms. Rat spinal microglia cells were isolated and inflammatory condition was stimulated by 24-h incubation with lipopolysaccharide (LPS). Rats were divided into 4 groups: sham, chronic constriction injury (CCI), CCI + miR-negative control (miR-NC) and CCI + miR-101 mimics. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) tests were conducted. The mRNA levels of key genes were determined by quantitative real-time polymerase chain reaction. Mammalian target of rapamycin (mTOR) protein level was detected by Western blot. Concentrations of interleukin (IL)-6, IL-1ß and tumor necrosis factor (TNF)-α were examined by ELISA. MiR-101 was downregulated and mTOR was upregulated in lumbar spinal dorsal horns from CCI rats. Targetscan and luciferase reporter assay confirmed that mTOR was direct target of miR101. MiR-101 mimics inhibited LPS-stimulated increase in the levels of IL-6, IL-1ß and TNF-α in primary microglial cells in vitro. In the rat CCI model, miR-101 mimics also suppressed CCI-induced decrease in PWT and PWL and inhibited CCI-induced increase in mRNA and protein levels of IL-6, IL-1ß and TNF-α. In addition, miR-101 downregulated mTOR mRNA and protein expressions in CCI rats. Besides, CCI operation resulted in miR-101 downregulation and mTOR mRNA upregulation in spinal microglia cells in a time-dependent manner. In conclusion, miR-101 had neuropathic pain-attenuating activity through targeting mTOR.

10.
Phys Chem Chem Phys ; 21(37): 21030-21037, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31528913

RESUMO

The control of surfactant adsorption/desorption, a fundamental process in colloid and surface chemistry, is of crucial importance for surfactant recycling and pollution-free waste treatment. Using first-principles simulations, we designed a photoswitchable approach to realize separation of a photoresponsive surfactant from the adsorbate. We chose a 4-butyl-(4'-(3-trimethylammoniumpropoxy)phenyl)azobenzene cation and quartz as the model system of a surfactant and adsorbate, respectively. Through first-principles calculations, we found that the trans isomer of the surfactant tends to assemble on the silica surface, while the cis isomer tends to be detached from the surface and is instead surrounded by water molecules. The chemical origin of the difference arises from the interactions between the surfactant and solvent, which depend on the molecular conformational change and associated redistribution of charges before and after the isomerization. Intriguingly, the interaction energy between the silica surface and the surfactant does not change significantly with the conformational change of the molecule. Meanwhile, an appreciable void space of the cis conformer attributed to the steric hindrance disfavors the assembling of surfactants on the silica surface, and its significant polarity favors the water environment, which prompts its desorption from the surface. The prediction from computations was then validated by experimental results. We expect our proof-of-concept study on the phototriggered separation of azobenzene-derived surfactant from a silica surface to provide an alternative way of achieving stimuli-responsive separation of surfactant from adsorbates.

11.
Waste Manag ; 99: 146-153, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31476639

RESUMO

The thermal degradation dynamics of new and aged PVC sheaths was studied in detail. The results illustrated that compared to new PVC sheath, the onset decomposition of aged PVC sheath mainly happened at higher temperature with larger peak value of mass loss rate. Three model-free methods most commonly used were employed to estimate the activation energy values at different conversions. It was noted that the aged PVC sheath exhibited greater entire activation energy than new PVC sheath. Two thermal degradation regions were observed based on the activation energy variation with conversion. The threshold of conversion for two regions was 0.6 for new PVC sheath and 0.5 for aged PVC sheath. The possible reaction mechanism was predicted by generalized master-plots method. The reaction model corresponding to each region showed observed difference between new and aged PVC sheaths. The compensation effect was also used to calculate the related pre-exponential factor. The variation of thermal degradation behavior could be ascribed to the changes of chemical composition, molecular structure, composition proportion and various additives after thermal aging. Besides, the thermal degradation process was reconstructed by an ANN model and it indicated that the predicted data fitted well with the experimental data.


Assuntos
Temperatura Alta , Cloreto de Polivinila , Cinética
12.
Biosci Rep ; 39(10)2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31537628

RESUMO

BACKGROUND: Candida is a fungus that causes various types of candidemia, which is the fourth major infectious disease of the blood system. MALDI-TOF-MS is a simple and rapid detection instrument. The aim of the present study was to verify the accuracy of MALDI-TOF-MS in detecting Candida. METHOD: A pooled analysis of articles on MALDI-TOF-MS for diagnosis of candidemia was performed. The quality of original research was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) guidelines. Stata 12.0 software was used to merge the correct identification rates of Candida and Candida subspecies and obtain pooled sensitivity and specificity of the diagnostic methods. Heterogeneity was found in the subgroup analysis of the included articles. Hence, we explored the factors causing the heterogeneity and its impact on the overall situation. Sensitivity analysis was used to examine the effect of Candida level on total response. Egger's test was used to evaluate the publication bias of the included articles. RESULTS: A total of 16 articles in Pubmed, 79 articles in Embase, 1 article in Cochrane Library, 30 articles in Web of Science and 3 from other sources were identified, of which 10 articles were included based on the inclusion and exclusion criteria. The overall identification accuracy was 100%. CONCLUSION: The accuracy of MALDI-TOF-MS for the identification of Candida was 100%. Further research is necessary to determine whether MALDI-TOF-MS can be used as a clinical diagnostic standard for the identification of Candida.

13.
Scand J Gastroenterol ; 54(8): 953-959, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31361977

RESUMO

Background: Acute mesenteric ischemia (AMI) is a rare life-threatening condition, especially for the patients with transmural intestinal necrosis (TIN). However, the optimal time for surgical intervention is controversial. As a series study, this study aimed to identify the outcomes and clinical characteristic of patients with TIN. Methods: Clinical data of 158 patients with AMI from January 2010 to December 2017 were retrospectively analyzed in a national gastrointestinal referral center in China to confirm the outcomes and identify predictors for TIN. Results: According to the results of pathological assessment and follow-up, 62 patients were TIN and 96 were non-TIN. Patients with TIN have a higher mortality and incidence of severe complications. The significant independent predictors for TIN were arterial lactate level (OR: 4.76 [2.29 ∼ 9.89]), free intraperitoneal fluid (OR: 9.49 [2.56 ∼ 35.24]) and pneumatosis intestinalis (OR: 7.08 [1.68 ∼ 29.82]) in computed tomography (CT) scan imaging. The overall area under the receiver operating characteristics (ROC) curve of the model was 0.934 (95% confidence interval: 0.893 ∼ 0.974). Using ROC curve, the cutoff value of arterial lactate level predicting the onset of TIN was 2.65 mmol/L. Conclusions: Patients concomitant with TIN manifest a higher risk of poor prognosis. The three predictors for TIN were arterial lactate level >2.65 mmol/L, free intraperitoneal fluid and pneumatosis intestinalis. Close monitoring these predictors would help identify AMI patients developed TIN and in urgent need for bowel resection.

14.
ACS Appl Mater Interfaces ; 11(33): 29569-29578, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31361117

RESUMO

Circulating tumor cells (CTCs) in blood is the direct cause of tumor metastasis. The isolation and detection of CTCs in the whole blood is very important and of clinical value in early diagnosis, postoperative review, and personalized treatment. It is difficult to separate all types of CTCs that efficiently rely on a single path due to cancer cell heterogenicity. Here, we designed a new kind of "filter chip" for the retention of CTCs with very high efficiency by integrating the effects of cell size and specific antigens on the surface of tumor cells. The filter chip consists of a semicircle arc and arrays and can separate large-scale CTC microspheres, which combined with CTCs automatically. We synthesized interfacial zinc oxide coating with nanostructure on the surface of the microsphere to increase the specific surface area to enhance the capturing efficiency of CTCs. Microspheres, trapped in the arrays, would entrap CTCs, too. The combination of the three kinds of strategies resulted in more than 90% capture efficiency of different tumor cell lines. Furthermore, it is easy to find and isolate the circulating tumor cells from the chip as tumor cells would be fixed inside the structure of a filter chip. To avoid the high background contamination when a few CTCs are surrounded by millions of nontarget cells, a digital detection method was applied to improve the detection sensitivity. The CTCs in the whole blood were specifically labeled by the antibody-DNA conjugates and detected via the DNA of the conjugates with a signal amplification. The strategy of the antibody-functional microsphere-integrated microchip for cell sorting and detection of CTCs may find broad implications that favor the fundamental cancer biology research, the precise diagnosis, and monitoring of cancer in the clinics.

15.
Disaster Med Public Health Prep ; : 1-11, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31317864

RESUMO

ABSTRACTGiven the non-repeatability, complexity, and unpredictability of unconventional public health emergencies, building accurate models and making effective response decisions based only on traditional prediction-response decision-making methods are difficult. To solve this problem, under the scenario-response paradigm and theories on parallel emergency management and discrete event system (DES), the parallel simulation decision-making framework (PSDF), which includes the methods of abstract modeling, simulation operation, decision-making optimization, and parallel control, is proposed for unconventional public health emergency response processes. Furthermore, with the example of the severe acute respiratory syndrome (SARS) response process, the evolutionary scenarios that include infected patients and diagnostic processes are transformed into simulation processes. Then, the validity and operability of the DES-PSDF method proposed in this paper are verified by the results of a simulation experiment. The results demonstrated that, in the case of insufficient prior knowledge, effective parallel simulation models can be constructed and improved dynamically by multi-stage parallel controlling. Public health system bottlenecks and relevant effective response solutions can also be obtained by iterative simulation and optimizing decisions. To meet the urgent requirements of emergency response, the DES-PSDF method introduces a new response decision-making concept for unconventional public health emergencies.

16.
J Phys Chem Lett ; 10(15): 4317-4322, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31310541

RESUMO

Hybrid heterostructures are a promising type of materials framework for optoelectronic conversion. We designed a ternary energy-dependent thin layer of Cu2S-Pt-WO3 (p-type-metal-n-type) heterojunction to explore an alternative way of realizing efficient charge separation. First-principles calculations showed that the Fermi level of the whole system is lined up via the mediation of Pt metal, which fosters the combination of holes in Cu2S and electrons in WO3 and keeps electrons in Cu2S and holes in WO3 well separated. Importantly, creation of band bending and charge polarization steer low-energy charges selectively to the intermediate metal and keep high-energy charges on individual semiconductors apart. Our simulation analysis of two-dimensional layers with the metal bridge shows increased charge flows across the junction compared to that of their bulk counterparts. Overall, this heterojunction is viable for suppressing recombination of photogenerated electron-hole pairs and augmented electrons per surface that would allow enhanced optoelectronic conversion.

17.
J Pharm Biomed Anal ; 175: 112738, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31362249

RESUMO

Turmeric (Curcuma longa L, Zingiberaceae) rhizomes exhibit versatile biological activities including the significant anti-cancer property. As an herbal medicine, the therapeutic effects of turmeric may be expressed by multi-components which have complicated integration effects on multi-targets. Therefore, having previously found three A549 cell-binding curcuminoids (curcumin, Cur; demethoxycurcumin, DMcur; bisdemethoxycurcumin, BMcur) from turmeric, studies were undertaken in this paper to determine the anti-cancer mechanism and integration effects of these curcuminoids by using chemical markers' knockout and UHPLC-LTQ Orbitrap MS-based metabolomics. Four curcuminoid-containing fractions including a mixture of 3 cell-binding curcuminoids (CE), and three individual curcuminoids with natural proportion in turmeric were prepared by chemical markers' knockout method. CE, Cur, DMcur and BMcur fractions showed significant anti-cancer activity on A549 cells. The activities of CE, Cur and BMcur fractions were comparative with the turmeric crude extract (TcE). In the metabolomics study, CE and three individual curcuminoid fractions changed the expression of 25 metabolites in A549 cells, which were involved in glycerophospholipid catabolism, sphingolipid metabolism and fatty acid metabolism, etc. Among them, glycerophospholipid catabolism was disordered greatly in CE group, while sphingolipid metabolism was suggested to be closely related to DMcur and BMcur activity. Furthermore, the metabolomics data showed that three curcuminoids existed synergistic and antagonistic actions and the use of multi-curcuminoids is more powerful than use of single curcuminoid on the metabolic alterations of A549 cells.

18.
Drug Alcohol Depend ; 202: 168-171, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31352306

RESUMO

BACKGROUND: Cocaine is a commonly abused drug and there is no approved medication specifically to treat its addiction or overdose. Bacterial cocaine esterase (CocE)-derived RBP-8000 is currently under clinical development for cocaine overdose treatment. It is proven to be effective for human use to accelerate cocaine metabolism into physiologically inactive products. Besides cocaine, RBP-8000 may hydrolyze the neurotransmitter acetylcholine (ACh), however, no study has reported its cholinesterase activity. The present study aims to examine RBP-8000's cholinesterase activity and substrate selectivity to address the potential concern that this enzyme therapy might produce cholinergic side-effects. METHODS: Both computational modeling and experimental kinetic analysis were carried out to characterize the potential cholinesterase activity of RBP-8000. Substrates interacting with RBP-8000 were modeled for their enzyme-substrate binding complexes. In vitro enzymatic kinetic parameters were measured using Ellman's colorimetric assay and analyzed by Michaelis-Menten kinetics. RESULTS: It is the first demonstration that RBP-8000 catalyzes the hydrolysis of acetylthiocholine (ATC). However, its catalytic efficiency (kcat/KM) against ATC is 1000-fold and 5000-fold lower than it against cocaine at 25 °C and 37 °C, respectively, suggesting RBP-8000 has the desired substrate selectivity for cocaine over ACh. CONCLUSION: Given the fact that clinically relevant dose of RBP-8000 displays insignificant cholinesterase activity relative to endogenous cholinesterases in human, administration of RBP-8000 is unlikely to produce any significant cholinergic side-effects. This study provides supplemental evidences in support of further development of RBP-8000 towards a clinically used pharmacotherapy for cocaine overdose.

19.
Cancer Sci ; 110(9): 2734-2747, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31278886

RESUMO

Lung cancer has the highest morbidity and mortality among all cancers. Discovery of early diagnostic and prognostic biomarkers of lung cancer can greatly facilitate the survival rate and reduce its mortality. In our study, by analyzing Gene Expression Omnibus and Oncomine databases, we found a novel potential oncogene uridine-cytidine kinase 2 (UCK2), which was overexpressed in lung tumor tissues compared to adjacent nontumor tissues or normal lung. Then we confirmed this finding in clinical samples. Specifically, UCK2 was identified as highly expressed in stage IA lung cancer with a high diagnostic accuracy (area under the receiver operating characteristic curve > 0.9). We also found that high UCK2 expression was related to poorer clinicopathological features, such as higher T stage and N stage and higher probability of early recurrence. Furthermore, we found that patients with high UCK2 expression had poorer first progression survival and overall survival than patients with low UCK2 expression. Univariate and multivariate Cox regression analyses showed that UCK2 was an independent risk factor related with worse DFS and OS. By gene set enrichment analysis, tumor-associated biological processes and signaling pathways were enriched in the UCK2 overexpression group, which indicated that UCK2 might play a vital role in lung cancer. Furthermore, in cytology experiments, we found that knockdown of UCK2 could suppress the proliferation and migration of lung cancer cells. In conclusion, our study indicated that UCK2 might be a potential early diagnostic and prognostic biomarker for lung cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Pulmonares/patologia , Recidiva Local de Neoplasia/diagnóstico , Uridina Quinase/metabolismo , Idoso , Linhagem Celular Tumoral , Proliferação de Células , Conjuntos de Dados como Assunto , Intervalo Livre de Doença , Feminino , Técnicas de Silenciamento de Genes , Humanos , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Uridina Quinase/genética
20.
Mol Carcinog ; 58(10): 1832-1845, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31219645

RESUMO

The cancer stem cells (CSCs) is a subset of cancer cells that possess stem cell properties, which plays a crucial role in the occurrence, metastasis, and recurrence of the tumor. XB130 is a novel adapter protein potentially serves as a functional factor in CSCs. To determine the role of CSCs in breast cancer, we focused on the study of XB130. In our study, we found that XB130 expression was significantly upregulated in breast cancer and was closely related to the clinicopathologic characteristics, overall survival and poor prognosis of breast cancer patients. Functionally, we found that knockdown of XB130 was not only played an important role in proliferation, epithelial-mesenchymal transition (EMT), and metastasis in breast cancer cells but also exhibited potent antitumor activity in animal tumor models. Moreover, we demonstrated that silencing endogenous XB130 regulated the cancer stem cell-like properties of breast cancer, including the formation of self-renewing spheres and the proportion of breast cancer SP+ cells. Mechanistically, our studies indicated that downregulation of XB130 restrained the EMT and Wnt/ß-catenin signaling, so as to weaken the tumor-initiating cell-like phenotype of breast cancer cells. This study indicates that XB130 plays an important role in maintaining the EMT and stem cell-like characteristics of breast cancer cells, supporting the significance of XB130 as a new potential therapeutic target for early diagnosis and prognosis of breast cancer.

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