Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 789
Filtrar
1.
Adv Healthc Mater ; : e2100311, 2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-33963820

RESUMO

Membrane camouflaged-nanoparticles (CM-NPs) have been exploited to inherit desired functionalities from source cells. Despite those advantages, membrane cloak may play a "double-edged sword" role in tumor-targeting therapy, as the intact membrane coating may hinder function-exertion of loaded drugs after reaching predetermined site. Therefore, further optimization of CM-NPs is still needed to enhance their delivery efficiency. Herein, natural product, Solamargine (SM), a cholesterol-affiliative amphiphilic potato alkaloid is first applied as core component of "inner core," to design a cell-mimicking "core-shell" nanoparticle (RBC-SLip) with acid-responsive off-coating properties for tumor-targeted therapy. Owing to red blood cell membrane (RBCm)-derived outer coating, it circulates stably in physiological conditions. While it would undergo an off-coating morphological change in response to acid stimuli in tumor microenvironment (TME), afterwards, the resulting off-coating liposome (SLip) shows active tumor-targeting and endosomal escape abilities, thus contributing to superior antitumor efficacy. In addition, SM also possesses natural TME-modulating ability; therefore, RBC-SLip can synergize with the PD1/PD-L1 blockade immunotherapy when encapsulated with PTX to achieve enhanced chemoimmunotherapy. The off-coating strategy developed by natural products SM, provide a brand-new perspective to optimize CM-NPs, and it also embodies application value of "unification of medicines and excipients" of natural products.

2.
Medicine (Baltimore) ; 100(18): e25639, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950941

RESUMO

BACKGROUND: Salvianolate, a common drug for stabilizing heart disease and Angina Pectoris, is considered to be off-label for preventing venous thromboembolism (VTE) or anticoagulation at present. However, many clinical studies have showed that salvianolate can effectively inhibit the deep-vein thrombosis (DVT) incidence, and prevent VTE of perioperative patients in the real world in China. OBJECTIVE: This analysis aimed to evaluate the effectiveness and safety of salvianolate in preventing VTE in perioperative patients. METHODS: Databases of PubMed, Cochrane Library, Embase, CNKI, Wanfang and VIP were searched until July 2019. Literature retrieval, data extraction and quality assessment were independently completed by two researchers and checked with each other. Review Manager 5.2 software was applied for meta-analysis. RESULTS: A total of 429 studies were retrieved, including 11 randomized controlled trials (RCTs) with a total of 1149 subjects. Compared with low molecular weight heparin (LMWH) group alone, salvianolate combined LMWH group had lower DVT incidence in preventing perioperative thrombosis (2.75% and 14.23%, OR: 0.21, 95% CI:[0.08,0.53]; P = .0009). The incidence of adverse reactions of experimental group was similar to that of control group (1.79% and 2.31%, OR: 0.65, 95% CI:[0.18,2.35]. P = .51). Compared with the control group, D-dimer level (D-D), platelet count (PLT), fibrinogen (FIB), whole blood high shear viscosity (WBHSV), and whole blood low shear viscosity (WBLSV) were all significantly decreased (P < .01), and prothrombin time (PT) was significantly increased (P < .05). CONCLUSION: Salvianolate combined LMWH has better effectiveness and the same safety in preventing venous thromboembolism in perioperative patients. However, due to the small number of included literatures, large sample studies are still needed to further verify this conclusion.

3.
BMC Med Educ ; 21(1): 266, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33971857

RESUMO

BACKGROUND: China is experiencing major medical education reforms that include establishing national training standards, standards for health professionals, and advanced health delivery system requirements. Graduate medical education (GME) is being piloted as a merger of Doctor of Medicine (MD) with PhD programs to improve academic research and clinical training. However, the academic degree-centred system has led to a preoccupation with research rather than clinical training. Unfortunately, there is a shortage of quality information regarding the clinical training of MD graduates from Chinese medical schools. To fill this gap, this general investigation aims to provide the perspective of recent MD graduates in China for the different subspecialties of clinical training as experienced in different contexts. METHODS: There were 432 MD graduates who participated in an online survey regarding their clinical training. Information collected included overall satisfaction, educational supervision, supervised learning events, curriculum coverage, local teaching, teamwork, educational governance, workload, supportiveness of the environment, feedback, clinical experience, patient safety, handovers, and reporting systems. RESULTS: Only 37.4% reported satisfaction with the overall clinical training quality; 54.6% rated the informal and bedside quality as "good"; 64.4% reported they knew who provided clinical supervision; but only 35.5% rated the quality of clinical supervision as high; 51.8% reported that they judged senior physicians as "not competent"; 41.9% agreed that the staff treated each other respectfully; 97.4% admitted that they worked beyond the mandatory hours and claimed they were regularly short of sleep; 84.2% raised concerns about patient safety; 45.3% reported that they received regular informal feedback; 48.1% believed that their concerns about education and training would be addressed. CONCLUSIONS: This study suggests that the quality of clinical training for MD graduates should be improved. While the overall satisfaction with the teaching quality was acceptable, the quality of many clinical training aspects scored poorly. A major problem seems an undue focus on research in MD/PhD training at the cost of the quality of clinical training, due to career perspectives that undervalue clinical competence. The findings of this study should benefit from a deeper investigation to understand the causes and possible remediation. Suggestions include defining subspecialties and training lengths; monitoring, evaluation, and integration SST with MD degree; providing funds or rewards for academic and clinical training; establishing supervising teams to guide clinical training; and establishing physician scientist task force to help overcome challenges.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33893718

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19) is having a dramatic effect on the mental health of healthcare workers (HCWs). Upon the emergence of the COVID-19 pandemic, the Chinese government dispatched about 42 000 HCWs to Wuhan City and Hubei Province to fight this pandemic. This study briefly examines front-line nurses who experienced burnout, with the main objective of investigating the mediating roles of positive and negative affect in the relationship between resilience and burnout in Wuhan hospitals at the peak of the COVID-19 pandemic. A total of 180 front-line nurses voluntarily participated via a social media group. They completed the online questionnaires, including the Maslach Burnout Inventory-General Survey (MBI-GS), the Positive and Negative Affect Schedule (PANAS), the Connor-Davidson Resilience Scale (CD-RISC), demographics, and work-related characteristics. Structural equation modelling (SEM) analysis was used to examine the mediating effect of positive and negative affect on the relationship between resilience and burnout. The total prevalence of burnout was 51.7%, of which 15.0% were severe burnout. These preliminary results revealed that positive and negative affect fully mediated the effects of resilience on burnout, emotional exhaustion, depersonalization, and reduced personal accomplishment of front-line nurses. It is necessary to know the impact of resilience on HCWs with burnout through the positive and negative affect of individual backgrounds and situations, and how policymakers can deploy resilience interventions to support front-line HCWs.

5.
Protein Cell ; 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33886094

RESUMO

N6-methyladenosine (m6A) on chromosome-associated regulatory RNAs (carRNAs), including repeat RNAs, plays important roles in tuning the chromatin state and transcription, but the intrinsic mechanism remains unclear. Here, we report that YTHDC1 plays indispensable roles in the self-renewal and differentiation potency of mouse embryonic stem cells (ESCs), which highly depends on the m6A-binding ability. Ythdc1 is required for sufficient rRNA synthesis and repression of the 2-cell (2C) transcriptional program in ESCs, which recapitulates the transcriptome regulation by the LINE1 scaffold. Detailed analyses revealed that YTHDC1 recognizes m6A on LINE1 RNAs in the nucleus and regulates the formation of the LINE1-NCL partnership and the chromatin recruitment of KAP1. Moreover, the establishment of H3K9me3 on 2C-related retrotransposons is interrupted in Ythdc1-depleted ESCs and inner cell mass (ICM) cells, which consequently increases the transcriptional activities. Our study reveals a role of m6A in regulating the RNA scaffold, providing a new model for the RNA-chromatin cross-talk.

6.
ACS Appl Mater Interfaces ; 13(17): 19625-19632, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33886270

RESUMO

Hen egg white lysozyme (HEWL) is frequently applied as a model protein for research on protein folding, unfolding, and fibrillization identified by featured fluorescent probes. Here, a series of hydrophilic, pH-sensitive tetraarylethene (TAE)-type AIEgens are synthesized via a geminal cross-coupling (GCC) reaction and evaluated for their capabilities of fluorescence sensing and super-resolution localization imaging of HEWL fibrils. With superior optical and sensing properties, the selected TAE-type AIEgen probe is weakly emissive in aqueous media, without dependence on the pH value and buffer concentration, but exhibits "turn-on" fluorescence upon interaction with HEWL amyloid fibrils in a spontaneous and reversible way that just meets the requirement of fluorescence random switching for super-resolution imaging. The selected probe has the strongest fluorescence response to HEWL amyloid fibrils exhibiting a limit of detection of 0.59 nmol/L and enables super-resolution fluorescence imaging of amyloid aggregates with a high resolution of 40 nm.

7.
Sci Total Environ ; 784: 147023, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33905937

RESUMO

Although there has been increasing research on water saving in China's industrial sector, with the proposal of different methods and enriching perspectives, not much has been studied about the sector's water-saving potential (WSP), especially in terms of a quantitative analysis. In this paper, a quantitative WSP model is proposed based on (a) economic costs minimization, (b) diffusion of water-saving technologies, (c) progressive water price policies, and (d) data availability. To transform exogenous variables into endogenous ones, we assumed technology depreciation and designed a water trading mechanism in a policy-limited scenario. By analysing the data of 2015, the WSP of chemical and steel industries in Tianjin was estimated as 16.128 MCM and 1.914 MCM with technology penetration and strict progressive water prices, while the WSP in Zhejiang province was estimated as 17.541 MCM and 3.108 MCM with the same level of technology penetration. This study could be a reference point for further research on evaluation of WSP of other industrial sectors and guide governments in drafting water-saving policies.

8.
Drug Des Devel Ther ; 15: 1441-1457, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33833503

RESUMO

Aim: White tip silver needle, a slightly fermented white tea, is abundant in flavonoids, and it has great significance in terms of D-galactose/lipopolysaccharide-induced aging in mice. Methods: We analyzed the antioxidant capacity of white tip silver needle flavonoids (WTSNF) in vitro, assessed the effects of WTSNF on organ indexes, pathological changes, liver function indexes, biochemical indicators, molecular biological indicators, and genes related to oxidation and inflammation. Results: Ultra-high performance liquid chromatography-tandem mass spectrometry results showed that WTSNF contained baicalin, kaempferol, kaempferide, quercetin, isorhamnetin, lespenephryl, and rutin. WTSNF showed strong scavenging ability for both 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) free radicals. Pathological analysis results showed that WTSNF reduced liver, kidney, and lung damage in mice with induced aging. In the serum and liver tissue, WTSNF effectively increased the antioxidant-related levels of superoxide dismutase, catalase, glutathione peroxidase, glutathione, and total antioxidant capacity and reduced the levels of aspartate aminotransferase, alanine aminotransferase, malondialdehyde and nitric oxide. WTSNF also reduced the inflammation-related levels of interleukin-6, interleukin-1 beta, tumor necrosis factor alpha (TNFα), and interferon gamma (IFN-γ) and increased the levels of interleukin-10 and interleukin-12. Furthermore, WTSNF upregulated the mRNA expression levels of cupro-zinc superoxide dismutase, manganese superoxide dismutase, catalase, glutathione peroxidase, interleukin-10, neuronal nitric oxide synthase, endothelial nitric oxide synthase, nuclear factor erythroid 2-related factor, heme oxygenase 1, NAD(P)H dehydrogenase [quinone] 1, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκB-α), and thioredoxin, while it downregulated the mRNA expression levels of interleukin-6, interleukin-18, interleukin-1 beta, TNFα, IFN-γ, inducible nitric oxide synthase, cyclooxygenase-2, and nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB). Conclusion: WTSNF is a high-quality natural product with antioxidative and anti-inflammatory properties that can inhibits D-galactose/lipopolysaccharide-induced aging in mice.

9.
J Air Waste Manag Assoc ; : 1-16, 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33689567

RESUMO

Malaysia, also known as a food haven, is currently facing an excessive food waste problem which poses a threat to the environment. The objective of this research is to study the factors that affect the behavioral intention of Malaysians to reduce food waste. This study employs the Theory of Planned Behavior (TPB) and the Norm Activation Model (NAM) to better understand the behavioral intention of Malaysians toward reducing food waste. A cross-sectional study was conducted, using 352 self-administered survey questionnaires. Data collected were analyzed through PLS-SEM analysis. The results show that awareness of consequences (AC) and ascription of responsibility (AR) influence personal norms, while attitude, perceived behavioral control, and personal norms (PN) have significant effect on behavioral intention (BI) to reduce food waste. Furthermore, PN partially mediates the relationship between AC and BI as well as AR and BI. This study offers critical insights which will benefit the Malaysian Government, Non-Governmental Organizations (NGOs), and other related parties in recognizing factors influencing the intention to reduce food waste which can be adopted to develop practical solutions to curb food waste in Malaysia.Implications: This study offers critical insights to the Malaysian Government, non-governmental organizations (NGOs), and other related parties in recognizing factors influencing the intention to reduce food waste which can be adopted to develop practical solutions to curb food waste in Malaysia.

10.
Nutr Cancer ; : 1-10, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33715541

RESUMO

Lentinan can lead to apoptosis of tumor cells and improve immune function. However, limited research focused on the immunogenic death regulation mechanism of lentinan on mouse H22 cells. The study aimed to explore the effect of Lentinan on the expression of immunogenic death-related proteins in mice H22 cells. MTT method was used to detect and evaluate the effect of 200-1000 µg/mL lentinan on the survival rate of H22 cells after 24 h, 48 h, and 72 h, respectively. Flow cytometry was employed to collect the apoptotic rate of lentinan at different concentrations (200-800µg/mL) on H22 cells for 48 h, and obtain the apoptotic rate of 600 µg/mL lentinan at different times (12-72 h). The effect of Lentinan on the expression of H22 Immunogenic Cell Death proteins was analyzed by ELISA and HPLC-MS afterward. Results suggest that lentinan cytotoxic and pro-apoptotic have a concentration-dependent manner with the H22 cells. Moreover, the rate of apoptosis increased significantly (P < 0.05) in 24 h. Lentinan can induce the expression of Calreticulin(CRT), High mobility protein 1(HMGB1), ATP and Heat shock protein 70 (HSP70) .Therefore, the antitumor effect of lentinan may be related to the regulation of immunogenic death-related protein expression, which was beneficial to the future development of liver cancer vaccines.

11.
Reprod Biomed Online ; 42(5): 901-908, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33771465

RESUMO

RESEARCH QUESTION: Could the mitochondrial DNA (mtDNA) copy number of cumulus cells be used as a biomarker of the potential of embryo implantation in good prognosis IVF patients? DESIGN: A prospective cohort study on good prognosis IVF patients from a large reproductive medicine centre. A total of 392 embryos from 61 cycles (including 31 implanted and 30 non-implanted cycles) were enrolled in the study. The corresponding cumulus cell mtDNA copy number of embryos was tested by real-time quantitative polymerase chain reaction. The corresponding cumulus cell mtDNA copy numbers were compared between implanted and non-implanted embryos and also compared between high quality and poor quality embryos. Then, a mitochondrial function assay including mitochondrial membrane potentials, concentration of reactive oxygen species (ROS) and ATP content of the corresponding cumulus cells were compared between high quality and poor quality embryos to verify the above experimental findings. RESULTS: For the same population, the mean cumulus cell mtDNA copy numbers for implanted and non-implanted embryos were 255.61 ± 81.02 and 254.50 ± 73.29 (P = 0.47), and those for high quality and poor quality embryos were 266.02 ± 98.56 and 295.71 ± 70.64 (P = 0.99), respectively. There was no significant difference in cumulus cell mtDNA copy number between implanted and non-implanted embryos or between high quality and poor quality embryos. The mitochondrial membrane potential, ROS levels and ATP content of the corresponding cumulus cells did not differ significantly between high quality and poor quality groups. CONCLUSIONS: Measurement of cumulus cell mtDNA copy number might not provide any advantage to embryo prioritization in good prognosis IVF patients. Any suggested link between cumulus cell mtDNA copy number and embryo implantation requires further validation.

12.
Emerg Microbes Infect ; 10(1): 472-480, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33657971

RESUMO

Pandemic influenza, typically caused by the reassortment of human and avian influenza viruses, can result in severe or fatal infections in humans. Timely identification of potential pandemic viruses must be a priority in influenza virus surveillance. However, the range of host species responsible for the generation of novel pandemic influenza viruses remains unclear. In this study, we conducted serological surveys for avian and human influenza virus infections in farmed mink and determined the susceptibility of mink to prevailing avian and human virus subtypes. The results showed that farmed mink were commonly infected with human (H3N2 and H1N1/pdm) and avian (H7N9, H5N6, and H9N2) influenza A viruses. Correlational analysis indicated that transmission of human influenza viruses occurred from humans to mink, and that feed source was a probable route of avian influenza virus transmission to farmed mink. Animal experiments showed that mink were susceptible and permissive to circulating avian and human influenza viruses, and that human influenza viruses (H3N2 and H1N1/pdm), but not avian viruses, were capable of aerosol transmission among mink. These results indicate that farmed mink could be highly permissive "mixing vessels" for the reassortment of circulating human and avian influenza viruses. Therefore, to reduce the risk of emergence of novel pandemic viruses, feeding mink with raw poultry by-products should not be permitted, and epidemiological surveillance of influenza viruses in mink farms should be urgently implemented.

13.
Bioresour Technol ; 329: 124909, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33684842

RESUMO

A consortium (HPP) with improved ability in biomass conversion was achieved by adjusting the proportion of Pseudoxanthomonas taiwanensis in a natural consortium (HP), but the mechanism behind was unknown. Herein, the diversities of microbial community structure and gene functions of the consortia were analyzed first, and found that HPP had a more balanced microbial structure with enriched gene pathways related to cellular processes, environmental information processing and metabolism. Then, key genes responsible for biomass conversion were further analyzed, finding that their abundance and distribution contributed to HPP's efficient biomass conversion. Finally, consolidated bioprocessing of agricultural wastes by HPP was carried out to verify its enhanced ability, and ethanol with the highest yield that was ever reported was achieved at 0.28 g/g. This is the first study which reported the underlying mechanisms for synergistic effects of microbial consortia, and will guide the artificial construction of complex microbial consortium for specific purpose.


Assuntos
Lignina , Xanthomonadaceae , Biomassa , Consórcios Microbianos
14.
Opt Express ; 29(3): 3458-3464, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33770943

RESUMO

High-speed, high-efficiency silicon photodetectors play important roles in the optical communication links that are used increasingly in data centers to handle the increasing volumes of data traffic and higher bandwidths required as use of big data and cloud computing continues to grow exponentially. Monolithic integration of the optical components with signal processing electronics on a single silicon chip is of paramount importance in the drive to reduce costs and improve performance. Here we report grating-enhanced light absorption in a silicon photodiode. The absorption efficiency is determined theoretically to be as high as 77% at 850 nm for the optimal structure, which has a thin intrinsic absorption layer with a thickness of 220 nm. The fabricated devices demonstrate a high bandwidth of 11.3 GHz and improved radio-frequency output power of more than 14 dB, thus making them suitable for use in data center optical communications.

15.
Med Sci Monit ; 27: e929389, 2021 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-33714972

RESUMO

BACKGROUND Accumulated evidence has suggested that hydrogen sulfide (H2S) has a role in bone formation and bone tissue regeneration. However, it is unknown whether the H2S content is associated with bone mineral density (BMD) in patients with osteopenia/osteoporosis. MATERIAL AND METHODS In the present study, we aimed to explore the changes of serum H2S in osteopenia and osteoporosis patients. We analyzed femur expression of cystathionine ß synthase (CBS), cystathionine γ lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), which are key enzymes for generating H2S. RESULTS Sixteen (16%) patients had osteopenia, 9 (9%) had osteoporosis, and 75 (75%) had normal BMD. In comparison with patients with normal BMD (controls), the serum levels of H2S were unexpectedly increased in patients with osteopenia and osteoporosis. This increase was much higher in patients with osteoporosis than in those with osteopenia. Serum H2S levels were negatively correlated with femoral BMD, but not lumbar BMD. Interestingly, the expression of CBS and CSE were downregulated in femur tissues in patients with osteoporosis, whereas the expression of 3-MST remained unchanged. Serum phosphorus levels, alkaline phosphatase, hemoglobin, and triglycerides were found to be closely associated with CBS and CSE scores in femur tissues. CONCLUSIONS Serum H2S levels and femur CBS and CSE expression may be involved in osteoporosis pathogenesis.

16.
Int Orthop ; 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33559052

RESUMO

PURPOSE: The semi-extended tibial intramedullary nailing method would enable easier and improved reductions for tibial fractures as well as facilitate fluoroscopic imaging; however, its in-articular nature remains controversial. The aim of this study was to compare the clinical and functional outcomes of the semi-extended infrapatellar (SEIP) approach and hyper-flexed infrapatellar (HFIP) approach for intramedullary nailing to treat tibial shaft fractures. METHODS: This study involved the retrospective analysis of the medical records of patients with tibial shaft fractures that were fixed through either the SEIP approach or the HFIP approach of intramedullary nailing and who were admitted to a level 1 trauma centre. The minimum patient follow-up period was 12 months and the clinical and functional outcomes were estimated at the 12-month visit. RESULTS: Of the 80 patients whose medical records were analyzed, 40 (50%) underwent SEIP nailing and the remaining 40 (50%) underwent the traditional HFIP nailing. Compared with the HFIP group, patients in the SEIP group had a higher Lysholm knee score (median, 92 [interquartile range, 88-95] vs median, 88 [interquartile range, 81-92]; p = .01), a shorter intra-operative fluoroscopy time (median, 93 [interquartile range, 78-105] s, vs median, 136 [interquartile range, 110-157] s; p < .001), and operation time (mean, 88.1 [SD, 17.8] min vs mean, 98.7 [SD, 19.3] min; p = .01). The VAS score was significantly lower in the SEIP group (median, 0; interquartile range, 0-0) than in the HFIP group (median, 0; interquartile range, 0-2) (p = .03). There were two cases (5%) in the SEIP group and 10 cases (25%) in the HFIP group of moderate AKP (p = .03). Meanwhile, there was no significant difference in malalignment, nonunion, delayed union, infection, and other complications, as well as SF-36 physical and mental scores. CONCLUSION: We found that the SEIP approach to tibia intramedullary nailing was superior to the HFIP approach based on the intra-operative and post-operative outcomes. Thus, this novel technique provides an infrapatellar option for semi-extended tibial nailing.

17.
Cell Transplant ; 30: 963689720985113, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33522306

RESUMO

Bladder cancer is one of the most common malignancies. The existence of bladder cancer stem cells (BCSCs) has been suggested to underlie bladder tumor initiation and recurrence. Propofol is a commonly used intravenous anesthetic. Here, we find that propofol can dramatically block the activation of Hedgehog pathway in BCSCs. The propofol strongly repressed the growth of cancer cells. Attenuated proliferation and enhanced apoptosis of tumor cells were observed upon propofol stimulation. Furthermore, propofol reduced the self-renewal ability of BCSCs as well as the tumor formation. In conclusion, propofol is potentially used as a novel therapeutic agent for bladder cancer by targeting self-renewal through inhibiting Hedgehog pathway.

18.
Phytomedicine ; 83: 153469, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33535128

RESUMO

BACKGROUND: Ischemic stroke is a multifactorial disease contributing to mortality and neurological dysfunction. Isoliquiritin (ISL) has been reported to possess a series of pharmacological activities including antioxidant, anti-inflammatory, antifungal, anti-depression, anti-neurotoxicity and pro-angiogenesis activities but whether it can be used for ischemic stroke treatment remains unknown. PURPOSE: The goal of this study is to explore its therapeutic effect on ischemic stroke and demonstrated the potential mechanism of ISL in zebrafish model. METHODS: Using the photothrombotic-induced adult zebrafish model of ischemic stroke, we visualized the telencephalon (Tel) and optic tectum (OT) infarction injury at 24 h post-light exposure for 30 min by TTC and H&E staining. The effect of ISL on neurological deficits was analyzed during open tank swimming by video tracking. The antioxidant activity against ischemia injury was quantified by SOD, GSH-Px and MDA assay. Transcriptome analysis of zebrafish Tel revealed how ISL regulating gene expression to exert protective effect, which were also been validated by real-time quantitative PCR assays. RESULTS: We found for the first time that the Tel tissue was the first damaged site of the whole brain and it showed more sensitivity to the brain ischemic damage compared to the OT. ISL reduced the rate of Tel injury, ameliorated neurological deficits as well as counteracted oxidative damages by increasing SOD, GSH-Px and decreasing MDA activity. GO enrichment demonstrated that ISL protected membrane and membrane function as well as initiate immune regulation in the stress response after ischemia. KEGG pathway analysis pointed out that immune-related pathways, apoptosis as well as necroptosis pathways were more involved in the protective mechanism of ISL. Furthermore, the log2 fold change in expression pattern of 25 genes detected by qRT-PCR was consistent with that by RNA-seq. CONCLUSIONS: Tel was highly sensitive to the brain ischemia injury in zebrafish model of ischemic stroke. ISL significantly exerted protective effect on Tel injury, neurological deficits and oxidative damages. ISL could regulate a variety of genes related to immune, apoptosis and necrosis pathways against complex cascade reaction after ischemia. These findings enriched the study of ISL, making it a novel multi-target agent for ischemic stroke treatment.

19.
Stem Cell Reports ; 16(3): 458-469, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33636112

RESUMO

A small subgroup of embryonic stem cells (ESCs) exhibit molecular features similar to those of two-cell embryos (2C). However, it remains elusive whether 2C-like cells and 2C embryos share similar epigenetic features. Here, we map the genome-wide profiles of histone H3K4me3 and H3K27me3 in 2C-like cells. We found that the majority of genes in 2C-like cells inherit their histone status from ESCs. Among the genes showing a switch in their histone methylation status during 2C-like transitions, only a small number acquire 2C-embryo epigenetic signatures. In contrast, broad H3K4me3 domains display extensive loss in 2C-like cells. Most of the differentially expressed genes display decreased H3K4me3 and H3K27me3 levels in 2C-like cells, whereas de novo H3K4me3 deposition is closely linked with the expression levels of upregulated 2C-specific genes. Taken together, our study reveals the unique epigenetic profiles of 2C-like cells, facilitating the further exploration of totipotency in the future.

20.
Toxicol Lett ; 343: 1-10, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33571620

RESUMO

AIMS: Both gefitinib and afatinib are epidermal growth factor tyrosine kinase inhibitors (EGFR-TKI) in the treatment of non-small cell lung cancer (NSCLC). It has been reported that gefitinib and afatinib could cause hepatotoxicity during the clinic treatment, therefore it is critical to investigate their hepatotoxicity systematically. In this study, zebrafish (Danio rerio) were used as model animals to compare the hepatotoxicity and their toxic mechanism. MAIN METHODS: The zebrafish transgenic line [Tg (fabp10a: dsRed; ela3l:EGFP) was used in this study. After larvae developed at 3 days post fertilization (dpf), they were put into different concentrations of gefitinib and afatinib. At 6 dpf, the viability, liver area, fluorescence intensity, histopathology, apoptosis, transaminase reflecting liver function, the absorption of yolk sac, and the expression of relative genes were observed and analyzed respectively. KEY FINDINGS: Both gefitinib and afatinib could induce the larvae hepatotoxicity dose-dependently. Based on the liver morphology, histopathology, apoptosis and function assessments, gefitinib showed higher toxicity, causing more serious liver damage. Both gefitinib and afatinib caused abnormal expressions of genes related to endoplasmic reticulum stress (ERS) pathway and apoptosis. For example, jnk, perk, bip, chop, ire1, bid, caspase3 and caspase9 were up-regulated, while xbp1s, grp78, bcl-2/bax, and caspase8 were down-regulated. The hepatotoxicity difference of gefitinib and afatinib might be due to the different expression level of related genes.


Assuntos
Afatinib/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/patologia , Embrião não Mamífero/efeitos dos fármacos , Gefitinibe/toxicidade , Fígado/efeitos dos fármacos , Inibidores de Proteínas Quinases/toxicidade , Animais , Animais Geneticamente Modificados , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/patologia , Peixe-Zebra/embriologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...