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1.
Int J Med Sci ; 18(1): 128-136, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390781

RESUMO

Background: Traumatic brain injury (TBI) is a sudden trauma on the head, in which severe TBI (sTBI) is usually associated with death and long-term disability. MicroRNAs (miRNAs) are potential biomarkers of diverse diseases, including TBI. However, few systematic reviews and meta-analyses have been conducted to determine the clinical value of miRNAs expression in TBI patients. Methods: We conducted this systematic review and meta-analysis study according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed, Embase, the Cochrane Library, Web of Science, from inception to August 26, 2020. We included articles written in English that have reported on the diagnostic value of miRNAs expression in TBI patients. We excluded studies that did not provided sufficient information to construct the 2×2 contingency table. Results: Eight studies investigating the diagnostic value of miRNA in TBI were analyzed in this study. The overall sensitivity, specificity and area under the curve (AUC) of miRNAs in diagnosis of TBI were 89% [95% confidence interval (CI): 0.84-0.93], 92% (95% CI 0.82-0.97) and 95% (95% CI 0.93-0.97). We found that panels of multiple miRNAs could improve the diagnostic accuracy of TBI. Samples from blood and brain tissue have significantly enhanced diagnostic accuracy, when compared with saliva. The AUC of miRNAs in severe TBI was 0.97, with 91% sensitivity and 92% specificity. Conclusion: This systematic review and meta-analysis demonstrated that miRNAs could be potential diagnostic markers in TBI patients. MiRNAs detected in blood and brain tissue display high accuracy for TBI diagnosis.

2.
BMC Pregnancy Childbirth ; 21(1): 41, 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33422050

RESUMO

BACKGROUND: Radiofrequency ablation (RFA) is recommended to prevent potential neurological injury or intrauterine foetal death (IUFD) of the co-twin(s) in complicated monochorionic (MC) pregnancies. However, the impacts of various indications on the pregnancy outcome following RFA remain unclear. This study aimed to determine how the indications influence the perinatal outcomes in complicated MC pregnancies undergoing radiofrequency ablation. METHODS: This was a retrospective cohort study performed in a single centre. All consecutive MC pregnancies treated with RFA between July 2011 and July 2019 were included. The adverse perinatal outcomes and the survival rate were analysed based on various indications. The continuous variables with and without normal distribution were compared between the groups using Student's t-test and Mann-Whitney U test, respectively, and for categorical variables, Chi-square and Fisher's exact tests were used. P < 0.05 indicated a significant difference. RESULTS: We performed 272 RFA procedures in 268 complicated MC pregnancies, including 60 selective intrauterine growth restriction (sIUGR), 64 twin-twin transfusion syndrome (TTTS), 12 twin reversed arterial perfusion sequence (TRAPs), 66 foetal anomaly and 66 elective foetal reduction (EFR) cases. The overall survival rate of the co-twin was 201/272 (73.9%). The overall technical successful rate was determined at 201/263 (76.7%). The IUFD rate in the co-twin was 20/272 (7.4%). The TTTS group had recorded the lowest survival rate (37/64, 57. 8%), and the survival rate was significantly correlated with Quintero stages (P = 0.029). Moreover, the sIUGR III subgroup had a lower survival rate compared with sIUGR II (55.6%, versus 84.3%). The subgroup of foetal anomaly of gastroschisis or exomphalos had the highest IUFD rate (4/10, 40%), followed by sIUGR III (2/9, 22.2%) and dichorionic triamniotic (DCTA) subgroup (8/46, 17.9%). In EFR group, eight IUFD cases were all coming from the DCTA subgroup and received RFA before 17 weeks. CONCLUSIONS: The perinatal outcome of RFA was correlated with the indications, with the lowest survival rate in TTTS IV and the highest IUFD incidence in abdominal wall defect followed by sIUGR III. Elective RFA after 17 weeks may prevent IUFD in DCTA pregnancies.

3.
Int J Cancer ; 148(5): 1106-1114, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32930403

RESUMO

Reasons behind the rapid increase of thyroid cancer (TC) in China are uncertain. We assessed the burden of TC and the role of access to screening and salt iodization. We analyzed two national databases in China: Hospital Quality Monitoring System (HQMS) and China Reinsurance Company (CRC) database. HQMS covered 1037 (44.3%) Class 3 hospitals and 76 263 617 Class 3 hospital inpatients in 2013 to 2017 and CRC covered 93 123 018 clients in 2000 to 2016. The proportion of TC inpatients among inpatients in HQMS and TC incidence in critical illness insurance buyers were used to evaluate the association with screening and iodine status. Between 2013 and 2017, the proportion of TC patients in HQMS with urban employee medical insurance and good access to screening increased sharply while there was little change among those with the other two forms of medical insurance. Across provinces, the proportion of TC inpatients in HQMS was positively correlated with per capita disposable income but not with median urinary iodine. Similar findings were observed in the CRC database. In 2017, approximately 1000 individuals were overdiagnosed with TC daily. We conservatively forecast that 5.1 million healthy individuals would become TC patients unnecessarily between 2019 and 2030. Our findings suggested the epidemic of TC in China was substantially underestimated. It was associated with screening but not with salt iodization.

4.
J Invest Dermatol ; 141(1): 152-163, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32619504

RESUMO

Phenformin is a drug in the biguanide class that was previously used to treat type 2 diabetes. We have reported the antitumor activities of phenformin to enhance the efficacy of BRAF-MAPK kinase-extracellular signal-regulated kinase pathway inhibition and to inhibit myeloid-derived suppressor cells in various melanoma models. Here we demonstrate that phenformin suppresses tumor growth and promotes keratinocyte differentiation in the 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate two-stage skin carcinogenesis mouse model. Moreover, phenformin enhances the suspension-induced differentiation of mouse and human keratinocytes. Mechanistically, phenformin induces the nuclear translocation of NFATc1 in keratinocytes in an AMPK-dependent manner. Pharmacologic or genetic inhibition of calcineurin and NFAT signaling reverses the effects of phenformin on keratinocyte differentiation. Taken together, our study reveals an antitumor activity of phenformin to promote keratinocyte differentiation that warrants future translational efforts to repurpose phenformin for the treatment of cutaneous squamous cell carcinomas.

5.
Food Chem ; 343: 128391, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33268181

RESUMO

Deoxynivalenol (DON) is found widely in foods and feeds that are contaminated with mildew and is one of the most harmful mycotoxins, threating not only human health but also impacting animal husbandry. Various physical, chemical and biological detoxification strategies have been applied in the past to reduce mycotoxin contamination. As a practical and economic method, addition of montmorillonite (Mt) offers the potential to eliminate mycotoxins, especially aflatoxin B1 (AFB1) and zearalenone (ZEA). Our study aimed to control DON, for the first time, using environmentally friendly Mt, modified with aluminum, iron and titanium via a pillaring effect to enlarge interlayer spacing. The materials were characterized using XRD, FTIR, SEM, EDS and BET. Spacing of the pillared Mt layers was shown to exceed that of raw Mt and could be tuned using the pillaring reagents (Al, Fe and Ti, 0.01 to 2.00 eq. relative to the cation exchange capacity of Mt). Adsorption of DON by pillared Mt was investigated using UPLC-MSMS (at pH 2.0 and 6.8). The results demonstrated that the adsorption ratios of 1.00-Al-Mt, 0.50-Fe-Mt and 1.00-Ti-Mt were 23.6%, 14.7% and 23.4%, respectively at pH 2.0 and 27.1%, 21.8%, and 27.4% correspondingly at pH 6.8 when added at 1.0 mg, which is 3-4 times higher than raw Mt (6.3-6.8% at pH 2.0 and 7.3-8.1% at pH 6.8). It was also found that with increased addition of pillared Mt (2.5 mg), the adsorption ratio approached 35%. The time for reaching equilibrium was approximately 120 min. These results demonstrated that Mt after pillaring modifications with Al, Fe and Ti can have potential for the control of DON in foods and feeds.

6.
Food Chem ; 338: 127846, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32836001

RESUMO

Cold storage is widely used for delaying ripening and senescence; however, fruit aroma diminishes noticeably after long-term cold storage. The esters synthesized by the lipoxygenase (LOX) pathway are responsible for 'Nanguo' pear aroma. As methyl jasmonate (MeJA) is known to act on various fruit qualities, we investigated whether it acts via the LOX pathway in cold-stored 'Nanguo' pears. MeJA treatment increased the content of volatile esters and unsaturated fatty acids and the activities of alcohol acyltransferase, alcohol dehydrogenase, and LOX. It also up-regulated the expression of key genes (PuAAT, PuADH3, PuADH5, PuADH9, PuLOX1, and PuLOX3) in the LOX pathway and that of transcription factors (PuMYB21-like, PuMYB108-like, PuWRKY61, PuWRKY72, and PuWRKY31), whose genes were differentially expressed in preliminary transcriptome analysis. Therefore, considering its effects on LOX pathway-related genes and transcription factors, MeJA may be useful in preventing cold-storage-induced decline in ester biosynthesis, aroma, and consequently the quality of cold-stored 'Nanguo' pears.


Assuntos
Acetatos/farmacologia , Ciclopentanos/farmacologia , Ésteres/metabolismo , Armazenamento de Alimentos/métodos , Oxilipinas/farmacologia , Pyrus/efeitos dos fármacos , Compostos Orgânicos Voláteis/metabolismo , Ácidos Graxos Insaturados/análise , Frutas/química , Frutas/efeitos dos fármacos , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Lipoxigenase/genética , Lipoxigenase/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas/genética , Proteínas/metabolismo , Pyrus/química , Pyrus/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
7.
Int Immunopharmacol ; 90: 107212, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33310666

RESUMO

BACKGROUND: The pathogenesis of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC) has not been fully elucidated. However, a strong correlation between IBD and high T helper 17 (Th17) levels has been found. Sirtuin 2 (SIRT2) has recently been found to play an important role in metabolic reprogramming, but its potential anti-inflammatory properties remain unclear. METHODS: The expression levels of SIRT2 and glucose metabolism-related proteins in peripheral blood mononuclear cells (PBMCs) of IBD patients and healthy volunteers were detected. Human PBMCs were differentiated into Th17 cells in vitro and were treated with TM simultaneously. The ratio of Th17 cells and apoptotic cells and the production of Interleukin (IL)-17A and the expression levels of transcription factors of classical signaling pathway related to Th17 differentiation were determined. The acetylation of LDHA and glucose metabolism was assessed. Subsequently, C57BL/6J colitis mice induced by 2.5% dextran sulfatesodiumsalt (DSS) were treated with or without TM, Disease activity index, T cell subsets in the mice spleen, relevant inflammatory cytokines in serum, specific mRNA, and proteins in mice colon were evaluated respectively. RESULTS: SIRT2 and glucose metabolism-related proteins in PBMCs of patients were overexpressed. Compared with the positive control group, human PBMCs treated with TM had lower levels of IL-17A, percentage of Th17 cells, levels of phospho-signal transducer and activator of transcription (p-STAT) 3 and phospho-nuclear transcription factor-κB (p-NF-κB), but higher levels of acetylated LDHA. Compared with colitis mice, TM-treated colitis mice had longer colons, reduced weight-losses, and lower disease activity index and histopathologic scores. Interestingly, although the expression levels of interferon (IFN)-γ, IL-17A, and retinoic acid receptor-related orphan receptor (ROR)-γt were inhibited in the colons of TM-treated colitis mice, the expression of forkhead box protein P3 (FOXP3) didn't change. Consistently, relative to the high percentage of splenic Th17 cells in colitis mice, the percentage of splenic Th17 cells in TM-treated colitis mice was as normal as PBS-treated mice, while the percentage of Treg cells was not affected. Additionally, the TM group had reduced levels of IL-23 and hypoxiainduciblefactor-1α (HIF-1α), and an increased level of IL-10 in the colon, compared with the colitis group. CONCLUSION: Our results indicate that TM reduces UC progression by reducing metabolic reprogramming and T cell differentiation. Specifically, TM prevented Th17 differentiation by reducing the expression of related transcription factors and promoting acetylation of LDHA (weakening glycolysis). SIRT2 may be a potential target for IBD treatment.

8.
Obes Facts ; : 1-13, 2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33352568

RESUMO

OBJECTIVES: The impact of heterogeneity on gender difference for achieving clinically meaningful weight loss (cmWL) remains unclear. Here, we explored the potential gender differences in factors associated with cmWL. METHODS: A total of 60,668 participants with body mass index (BMI) ≥25 kg/m2 at study entry and available BMI values at follow-up were included in this study. cmWL was defined as a weight loss of ≥5% from the study entry to follow-up. The associations of social-demographic factors, personal history of chronic diseases, lifestyle behaviors, and history of BMI with cmWL were evaluated using logistic regression models. RESULTS: During a median follow-up of 9.13 years, 26.6% of the participants had a cmWL (30.8% for females vs. 23.1% in males; p < 0.001). Participants with older age, obesity at study entry, being more physical activity compared to 10 years ago, being relapsed smokers or consistent current smokers, having a history of chronic diseases (i.e., diabetes, osteoporosis, and stroke), cancer diagnosis during the study period, and more than 10-year follow-up were more likely to achieve cmWL in both males and females (all p < 0.05). The new smoking quitters and participants with less active in physical activity compared to 10 years ago were less likely to achieve cmWL in both males and females (all p < 0.05). Specifically, males with a history of emphysema were more likely to reach cmWL, and for females, those being overweight at 20 years old and current drinkers were more likely to reach cmWL (p < 0.05). Sensitivity analyses demonstrated similar results. CONCLUSION: Age, BMI status, physical activity, smoking status, family income, and health status were independent factors in males and females for weight management. However, further well-designed prospective studies are warranted to confirm our findings.

9.
J Med Chem ; 63(24): 15852-15863, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33291877

RESUMO

To validate the hypothesis that Tyr748 is a crucial residue to aid the discovery of highly selective phosphodiesterase 8A (PDE8A) inhibitors, we identified a series of 2-chloroadenine derivatives based on the hit clofarabine. Structure-based design targeting Tyr748 in PDE8 resulted in the lead compound 3a (IC50 = 0.010 µM) with high selectivity with a reasonable druglike profile. In the X-ray crystal structure, 3a bound to PDE8A with a different mode from 3-isobutyl-1-methylxanthine (a pan-PDE inhibitor) and gave a H-bond of 2.7 Å with Tyr748, which possibly interprets the 220-fold selectivity of 3a against PDE2A. Additionally, oral administration of compound 3a achieved remarkable therapeutic effects against vascular dementia (VaD), indicating that PDE8 inhibitors could serve as potential anti-VaD agents.

10.
J Infect Dev Ctries ; 14(11): 1231-1237, 2020 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-33296333

RESUMO

INTRODUCTION: The outbreak of COVID-19 has spread worldwide. The evidence about risk factors of healthcare workers who infected COVID-19 is limited. This study aims to describe characteristics and influencing factors of the COVID-19 infection in healthcare workers. METHODOLOGY: The study was performed among COVID-19 infected and uninfected healthcare workers in three hospitals in Wuhan. A total of 325 healthcare workers participated; among them 151 COVID-19-infected healthcare workers were included. Characteristics of infected healthcare workers, and influencing factors including exposure histories, the use of protective equipment in different risk conditions and areas, perceptions, emotions, satisfactions and educations were described and analyzed. RESULTS: Healthcare workers got infected clustered mostly in the physical examination center. When performing general operations on confirmed or suspected patients, the use of protective equipment including the effectiveness of masks (p < 0.001), gloves (p < 0.001); and the use of gloves (p < 0.001), suits (p < 0.001), gowns (p < 0.001), shoe covers (p < 0.001), and hats (p < 0.001) were protective factors. The use of protective equipment was a protective factor in most cases. Negative emotions and dissatisfaction to the hospital response were associated with the increased risk of infection. CONCLUSIONS: The use of protective equipment, emotions and satisfactions to hospital responses are key COVID-19-infected factors. The awareness, the supply and the use of protective equipment, the layout of departments and other environmental and management factors should be strictly equipped. In addition, hospitals should also pay attention to emotions and satisfaction of healthcare workers.


Assuntos
/transmissão , Pessoal de Saúde/estatística & dados numéricos , Transmissão de Doença Infecciosa do Paciente para o Profissional , Adulto , Estudos de Casos e Controles , China , Feminino , Pessoal de Saúde/psicologia , Departamentos Hospitalares/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Equipamento de Proteção Individual/estatística & dados numéricos , Fatores de Risco , Inquéritos e Questionários
11.
Plant Biotechnol J ; 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33319456

RESUMO

Retention of flesh texture attributes during cold storage is critical for the long-term maintenance of fruit quality. The genetic variations determining flesh firmness and crispness retainability are not well understood. The objectives of this study are to identify gene markers based on quantitative trait loci (QTLs) and to develop genomics-assisted prediction (GAP) models for apple flesh firmness and crispness retainability. Phenotype data of 2664 hybrids derived from three Malus domestica cultivars and a M. asiatica cultivar were collected in 2016 and 2017. The phenotype segregated considerably with high broad-sense heritability of 83.85% and 83.64% for flesh firmness and crispness retainability, respectively. Fifty-six candidate genes were predicted from the 62 QTLs identified using bulked segregant analysis and RNA-seq. The genotype effects of the markers designed on each candidate gene were estimated. The genomics-predicted values were obtained using pyramiding marker genotype effects and overall mean phenotype values. Fivefold cross-validation revealed that the prediction accuracy was 0.5541 and 0.6018 for retainability of flesh firmness and crispness, respectively. An 8-bp deletion in the MdERF3 promoter disrupted MdDOF5.3 binding, reduced MdERF3 expression, relieved the inhibition on MdPGLR3, MdPME2, and MdACO4 expression, and ultimately decreased flesh firmness and crispness retainability. A 3-bp deletion in the MdERF118 promoter decreased its expression by disrupting the binding of MdRAVL1, which increased MdPGLR3 and MdACO4 expression and reduced flesh firmness and crispness retainability. These results provide insights regarding the genetic variation network regulating flesh firmness and crispness retainability, and the GAP models can assist in apple breeding.

12.
Sci Total Environ ; 760: 144316, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33341640

RESUMO

Microplastic pollution in marine environments is of particular concern on its risk to the ecosystem. To assess and manage microplastic contaminants, their quantitative detection in environmental samples is a high priority. However, uncertainties of current methods still exist when estimating their abundances, particularly with fine-grained (<1 mm) microplastics. This work reports a novel thermoanalytical method for quantifying microplastics by measuring the contents of microplastic-derived carbon (MPC) in samples under the premise of nearly eliminating the limit of their particle appearances. After validating the method via samples with the spiked microplastics, we have conducted a case study on sediment core H43 that spanned 1925-2009 CE from the Yellow Sea for further illustrating the high reliability and practicability of this method for quantifying microplastics in natural samples. Our results have demonstrated that the proposed method may be a promising technique to determine the mass-related concentrations of the total microplastics in marine sediments for evaluating their pollution status and quantitative contribution to marine carbon storage.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33349447

RESUMO

OBJECTIVES: The purpose of this study was to evaluate the postrelapse survival of relapsed osteosarcoma with pulmonary metastases in patients who received pulmonary metastasectomy using intent to treat and propensity score analysis. METHODS: Patients with osteosarcoma who relapsed with pulmonary metastases between 2004 and 2018 who were treated in a hospital affiliated with a medical school were included. All the enrolled patients were evaluated as operable with assessment algorithm at the time of diagnosis of pulmonary relapse and intent to treat analysis was done. Multiple propensity score methods (eg, matching, stratification, covariate adjustment, and inverse probability of treatment weighting) were performed to balance confounding bias. Cox proportional hazards regression and the Kaplan-Meier method were used to evaluate patient survival. RESULTS: A total of 125 patients met the study criteria. Of these, 59 (47.2%) patients received pulmonary metastasectomy combined with chemotherapy and 66 (52.8%) received chemotherapy alone. The 2-year and 5-year postrelapse survival rate of metastasectomy group and nonmetastasectomy group were 68.4% versus 25.0% and 41.0% versus 0%, respectively. The median postrelapse survival was 24.9 versus 13.5 months, respectively. Pulmonary metastasectomy was independently associated with improved survival (hazard ratio, 0.185; 95% confidence interval, 0.103-0.330; P < .001). These results were confirmed by multiple propensity score analyses. Further stratified analysis revealed that the survival advantage associated with metastasectomy was not significant in patients with metastases involving ≥3 lung lobes and patients with very high pretreatment serum alkaline phosphatase (more than twice the upper limit). CONCLUSIONS: Pulmonary metastasectomy is associated with improved survival in patients with recurrent osteosarcoma.

14.
Nat Commun ; 11(1): 6354, 2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33311485

RESUMO

The formation of zygote is the beginning of mammalian life, and dynamic epigenetic modifications are essential for mammalian normal development. H3K27 di-methylation (H3K27me2) and H3K27 tri-methylation (H3K27me3) are marks of facultative heterochromatin which maintains transcriptional repression established during early development in many eukaryotes. However, the mechanism underlying establishment and regulation of epigenetic asymmetry in the zygote remains obscure. Here we show that maternal EZH2 is required for the establishment of H3K27me3 in mouse zygotes. However, combined immunostaining with ULI-NChIP-seq (ultra-low-input micrococcal nuclease-based native ChIP-seq) shows that EZH1 could partially safeguard the role of EZH2 in the formation of H3K27me2. Meanwhile, we identify that EHMT1 is involved in the establishment of H3K27me2, and that H3K27me2 might be an essential prerequisite for the following de novo H3K27me3 modification on the male pronucleus. In this work, we clarify the establishment and regulatory mechanisms of H3K27me2 and H3K27me3 in mouse zygotes.


Assuntos
Genoma , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/metabolismo , Zigoto/metabolismo , Animais , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Epigenômica , Heterocromatina , Histona-Lisina N-Metiltransferase/genética , Masculino , Metilação , Camundongos , Camundongos Endogâmicos ICR , Camundongos Knockout , Nuclease do Micrococo , Oogênese/fisiologia , Complexo Repressor Polycomb 2/genética , Processamento de Proteína Pós-Traducional
15.
Brain Behav ; : e01918, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33295701

RESUMO

OBJECTIVE: To explore the effect of RTA-408 on the propofol-induced cognitive impairment of neonatal mice via regulating Nrf2 and NF-κB p65 nuclear translocation. METHODS: C57BL/6 neonatal mice were randomized into intralipid, propofol, vehicle + propofol, and RTA-408 + propofol groups. The learning and memory ability was inspected by Morries water maze (MWM) test. TUNEL staining was performed to examine the apoptosis of neurons in hippocampus. The gene and protein expressions in hippocampus were detected by immunohistochemistry, qRT-PCR, or Western blotting. The activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were tested by the corresponding kits. RESULTS: Propofol prolonged escape latency of mice, decreased the times of crossing the platform, and shortened the time of staying in the target quadrant, while RTA-408 treatment improved the above-mentioned situation. Besides, Nrf2 protein in hippocampus of mice induced by propofol was decreased with the increased NF-κB p65 nuclear translocation, which was reversed by RTA-408. Meanwhile, RTA-408 decreased the apoptosis of neurons accompanying with the down-regulation of Caspase-3 and the up-regulations of neuronal-specific nuclear protein (NeuN), microtubule-associated protein 2 (Map2), Ca2 + /Calmodulin-dependent Protein Kinase II (CaMKII), and parvalbumin (PV) immunostaining in hippocampus. Besides, propofol-induced high levels of proinflammatory cytokines and antioxidase activities in hippocampus were reduced by RTA-408. CONCLUSION: RTA-408 improved propofol-induced cognitive impairment in neonatal mice via enhancing survival of neurons, reducing the apoptosis of hippocampal neurons, mitigating the inflammation and oxidative stress, which may be correlated with the activation of Nrf2 and the inhibition of NF-κB p65 nuclear translocation.

16.
Ann Palliat Med ; 9(6): 4119-4126, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33302672

RESUMO

BACKGROUND: To further the exploration of the pathogenesis of mild cognitive impairment (MCI), we aimed to determine the appropriate dose for a rapidly established MCI rat model using D-galactose (D-gal), with lasting cognitive effects. METHODS: In Experiment 1, we evaluated various D-gal concentrations (100-2,000 mg/kg/day), and determined that, compared with saline injections of the same volume. In Experiment 2, we evaluated the duration of the effect of 1,000 mg/kg/day D-gal injections for 1 week, with MWM testing initiated at 1 day, 1 month, and 3 months after completion of the injection regime in three model groups, respectively. RESULTS: In Experiment 1, D-gal injections at a concentration of 1,000 mg/kg/day for 1 week was adequate to induce a significantly worse Morris water maze (MWM) test performance and pathomorphologic changes in the hippocampus, with MWM testing initiated 1 day after completion of the injection regime. In Experiment 2, Before modeling, the overall condition (fur, mental state, foraging behavior, and activity level), body weight, swimming speed, and swimming time did not significantly differ between the control (saline injections) and model groups (D-gal injections). After modeling, MWM test performance was considerably worse (longer escape latencies and fewer platform crossings within 90 seconds) in the model groups than in the control group, without significant differences among model groups. Furthermore, movement trajectories were similar among model groups. CONCLUSIONS: These results demonstrate that subcutaneous injections of D-gal 1,000 mg/kg/day for 1 week produce changes consistent with the characteristics and pathological processes of MCI. Thus, high-dose D-gal injection allows the rapid establishment of an MCI model that is effective and sustainable.

17.
Adv Sci (Weinh) ; 7(23): 2003370, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33304769

RESUMO

It is demonstrated that a novel eutectic solution including 1,3,5-trioxane (TXE) and succinonitrile (SN) can be converted into solid-state polymer electrolyte (SPE) via in situ polymerization triggered by lithium difluoro(oxalato)borate (LiDFOB). It is worth noting that all the precursors (LiDFOB, TXE, and SN) of this novel SPE are totally solid and nonvolatile at room temperature, where, LiDFOB works as a lithium salt and an initiator simultaneously to avoid the introduction of impurity. It is noted that such SPE presents a considerable ionic conductivity of 1.14 × 10-4 S cm-1 and a sufficiently wide electrochemical window of 4.5 V, which is significant for supporting the high-energy lithium batteries. In addition, this dedicatedly designed in situ polymerization is powerful to build kinetically favorable polymer-based protective layers on LiCoO2 cathode and Li metal anode simultaneously, guaranteeing outstanding cycling stability (capacity retention of 88% after 200 cycles) of 4.3 V LiCoO2/lithium metal batteries at room temperature. More intriguingly, soft packed LiCoO2/SPE/Li metal batteries can still light a blue light emitting diode (LED) under the harsh conditions of being bent, cut, and stroked by a hammer, demonstrating excellent safety characteristics.

18.
ACS Biomater Sci Eng ; 6(10): 5866-5873, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33320575

RESUMO

Preeclampsia has impacted 3-5% pregnancies among the world and its complications lead to both maternal and fetal morbidity and mortality. However, management of preeclampsia is limited. Nanoparticles targeting chondroitin sulfate A (CSA) can deliver drugs to placenta. Inactivation of soluble fms-like tyrosine kinase (sFlt-1) and nuclear factor-erythroid 2-like 2 (Nrf2) has been proved to alleviate preeclampsia and improve maternal and fetal outcomes. Carboxyl-polyethylene glycol-poly (d,l-lactide) (COOH-PEG5K-PLA8K), cationic lipid DOTAP, and siNrf2 and sisFlt-1 were used to construct the nanoparticles and conjugating peptides targeting CSA was fabricated to it. The expression levels of proteins and RNAs were estimated by qRT-PCR and Western blot assays. ELISA assays were performed to evaluate levels of circulating sFlt-1. The nanoparticles containing siNrf2 and sisFlt-1 are targeted to the placenta trophoblasts and downregulated the expression levels of Nrf2 and sFlt-1 as well as their downstream genes in the placental cells of model mice. Treatment of nanoparticles induced the expression of angiogenic factors in placenta. Knocking down Nrf2 and sFlt-1 synchronously alleviated the preeclampsia and increased the maternal and fetal outcomes in preeclampsia model mice. Nanoparticle-mediated simultaneous downregulation of placental Nrf2 and sFlt1 improved maternal and fetal outcomes in a preeclampsia mouse model.

19.
Anticancer Drugs ; 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33323682

RESUMO

Activation and proliferation of cancer stem cells exert an important role in the invasion, metastasis, and recurrence of malignant tumors, including lung cancer. Therefore, exploring molecular targets related to self-renewal and mobility of lung cancer stem cells has important clinical significance. In our present study, we aimed to explore the effects of miR-138-5p on lung cancer stem-like cells and associated regulatory mechanism. In our present study, enhanced self-renewal capacity and elevated expression of cancer stem cells markers CD133, CD44, aldehyde dehydrogenase 1 of lung cancer stem-like cells derived from A549 cells were firstly verified. Then, obviously enhanced autophagy was found in lung cancer stem-like cells compared with parental cells A549. Besides, we found that enhanced autophagy induced by rapamycin promoted self-renewal and cell mobility of lung cancer stem-like cells and suppression of autophagy by 3-methyladenine exerted just opposite effects. In addition, miR-138-5p was found to be downregulated in lung cancer stem-like cells compared with that in parental cell A549. At the same time, overexpression of miR-138-5p by transfected with miR-138-5p mimic was found to effectively suppress self-renewal and invasion of lung cancer stem-like cells. Further study revealed that ATG7 was a target of miR-138-5p and overexpressed miR-138-5p suppressed ATG7-mediated autophagy. In addition, specific small interference RNA-ATG7 strengthened the inhibiting effect of miR-138-5p mimic on self-renewal and invasion of lung cancer stem-like cells. Taken together, we found that autophagy helped to maintain self-renewal and invasion ability of lung cancer stem-like cells and overexpressed miR-138-5p exerted anti-tumor effects by blocking the self-renewal and invasion of lung cancer stem-like cells through suppressing ATG7-mediated autophagy.

20.
J Fish Dis ; 2020 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-33340375

RESUMO

Rapid and user-friendly diagnostic tests are necessary for early diagnosis and immediate detection of diseases, particularly for on-site screening of pathogenic microorganisms in aquaculture. In this study, we developed a dual-sample microfluidic chip integrated with a real-time fluorogenic loop-mediated isothermal amplification assay (dual-sample on-chip LAMP) to simultaneously detect 10 pathogenic microorganisms, that is Aeromonas hydrophila, Edwardsiella tarda, Vibrio harveyi, V. alginolyticus, V. anguillarum, V. parahaemolyticus, V. vulnificus, infectious hypodermal and haematopoietic necrosis virus, infectious spleen and kidney necrosis virus, and white spot syndrome virus. This on-chip LAMP provided a nearly automated protocol that can analyse two samples simultaneously, and the tests achieved limits of detection (LOD) ranging from 100 to 10-1  pg/µl for genomic DNA of tested bacteria and 10-4 to 10-5  pg/µl for recombinant plasmid DNA of tested viruses, with run times averaging less than 30 min. The coefficient of variation for the time-to-positive value was less than 10%, reflecting a robust reproducibility. The clinical sensitivity and specificity were 93.52% and 85.53%, respectively, compared to conventional microbiological or clinical methods. The on-chip LAMP assay provides an effective dual-sample and multiple pathogen analysis, and thus would be applicable to on-site detection and routine monitoring of multiple pathogens in aquaculture.

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