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1.
J Mol Med (Berl) ; 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32198625

RESUMO

The rapid advancement of genome editing technologies has opened up new possibilities in the field of medicine. Nuclease-based techniques such as the CRISPR/Cas9 system are now used to target genetically linked disorders that were previously hard-to-treat. The CRISPR/Cas9 gene editing approach wields several advantages over its contemporary editing systems, notably in the ease of component design, implementation and the option of multiplex genome editing. While results from the early phase clinical trials have been encouraging, the small patient population recruited into these trials hinders a conclusive assessment on the safety aspects of the CRISPR/Cas9 therapy. Potential safety concerns include the lack of fidelity in the CRISPR/Cas9 system which may lead to unintended DNA modifications at non-targeted gene loci. This review focuses modifications to the CRISPR/Cas9 components that can mitigate off-target effects in in vitro and preclinical models and its translatability to gene therapy in patient populations.

2.
Int Immunopharmacol ; 82: 106354, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32143008

RESUMO

The 5-hydroxytryptamine (5-HT) receptor is significant for the regulation of mood and memory. However, the role of 5-HT1AR in ß-Amyloid protein (Aß)-induced cognitive decline, neuroinflammation and the possible mechanism remains elusive. Thus, we aimed to evaluate the effects of 5-HT1AR on Aß-induced learning and memory decline and neuroinflammation in mice. Novel object recognition and Morris water maze tests were performed to observe learning and memory behavior in mice. Protein levels of Iba1, GFAP, MAP2, TNF-α, Tß4, C-fos, IKK-ß, IKB-α, NF-κBp65, phospho-NF-κBp65 in the hippocampus were examined by immunostaining or western blotting. Aß1-42-treatment inducing learning and memory decline was shown in novel object recognition and Morris water maze tests; neuroinflammation shown in immunostaining. Our study found out that 5-HT1AR inhibitor WAY100635 showed significant improvement in Aß-induced learning and memory decline. Moreover, WAY100635 decreases levels of Iba1, GFAP, and TNF-α in the hippocampus, which were related to neuroinflammation. While treatment with 5-HT1AR agonist 8-OH-DPAT or ERK inhibitor U0126 exerted no effects or even aggravated Aß-induced learning and memory decline. In addition, WAY100635 could downregulate phospho-NF-κB in the hippocampus of Aß1-42-injected mice. These results provide new insight into the mechanism, for 5-HT1AR in Aß-induced cognitive impairments through crosstalk with the NF-κB signaling pathway. Our data indicated that WAY100635 was involved in the protective effects against neuroinflammation and improvement of learning and memory in Alzheimer's disease.

3.
Yi Chuan ; 42(2): 222-229, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32102778

RESUMO

General education is an important part in higher education, which emphasizes the educational idea of integration of generality with specialty, and practices people-oriented education concept. However, there are some difficulties and puzzles in general education. Now the general education system with Chinese characteristics is needed to be established through practice and development. In this paper, we enumerate how to integrate knowledge of human genetics in practice of general education, teaching cases, and relevant analysis with concepts of general education. Using questions as "what are human beings?" as a leverage, we introduce teaching contents closely related to daily life. For example, we explain the past, present and future of human beings through contemporary evolutionary genomics teaching. In addition, we introduce problem-based deep thinking for students, thus integrating classical attributes of human beings into general education.


Assuntos
Currículo , Genética Humana/educação , Ensino , Humanos , Conhecimento , Estudantes
4.
Sci China Life Sci ; 63(3): 375-387, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32048161

RESUMO

Inflammatory leukocytes infiltration is orchestrated by mechanisms involving chemokines, selectins, addressins and other adhesion molecules derived from endothelial cells (ECs), but how they respond to inflammatory cues and coordinate leukocyte transmigration remain elusive. In this study, using hepatic ischemia/reperfusion injury (HIRI) as a model, we identified that endothelial Notch activation was rapidly and dynamically induced in liver sinusoidal endothelial cells (LSECs) in acute inflammation. In mice with EC-specific Notch activation (NICeCA), HIRI induced exacerbated liver damage. Consistently, endothelial Notch activation enhanced neutrophil infiltration and tumor necrosis factor (TNF)-α expression in HIRI. Transcriptome analysis and further qRT-PCR as well as immunofluorescence indicated that endomucin (EMCN), a negative regulator of leukocyte adhesion, was downregulated in LSECs from NICeCA mice. EMCN was downregulated during HIRI in wild-type mice and in vitro cultured ECs insulted by hypoxia/re-oxygenation injury. Notch activation in ECs led to increased neutrophil adhesion and transendothelial migration, which was abrogated by EMCN overexpression in vitro. In mice deficient of RBPj, the integrative transcription factor of canonical Notch signaling, although overwhelming sinusoidal malformation aggravated HIRI, the expression of EMCN was upregulated; and pharmaceutical Notch blockade in vitro also upregulated EMCN and inhibited transendothelial migration of neutrophils. The Notch activation-exaggerated HIRI was compromised by blocking LFA-1, which mediated leukocyte adherence by associating with EMCN. Therefore, endothelial Notch signaling controls neutrophil transmigration via EMCN to modulate acute inflammation in HIRI.

5.
Org Lett ; 22(3): 873-878, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31916771

RESUMO

New chalcone-based pyridinium salts have been successfully exploited, which could smoothly participate in the highly diastereoselective dearomatization with binucleophilic enaminones by taking advantage of their multiple reactive sites to construct bibridged benzoazepines in up to 89% yields. The key to the success was the skillful and unprecedented C-3 functionalization of the new pyridinium salts. This work not only provides a kind of novel pyridinium salt synthon but also achieves the first C-3 functionalization of pyridinium salts to construct complex and challenging bibridged benzoazepines with high synthetic efficiency.

6.
Ecotoxicol Environ Saf ; 191: 110200, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31958629

RESUMO

Cadmium (Cd) contamination in paddy soils and the related pollution risk of rice grain have received increasing attention. Agronomic measures, such as the application of sulfur and changes in water regimes, were reported to mitigate the accumulation of Cd in rice. However, there is limited information on the combined effects of sulfur application and water regimes. Therefore, a pot experiment was conducted to investigate the effects of two sulfur forms, three water regimes and multiple sulfur application rates on Cd accumulation in rice. The sulfur was applied as SO42- (SVI, replacing the traditional fertilizers by SO42--containing fertilizers), and element S (S0) was applied at 0, 10, 20, 30 and 40 mg S kg-1 soil. The water regimes were continuous flooding (F), flooding-moist alternation (FM), and moist irrigation (M), for a total of 30 treatments. The results indicated that application of SVI exceeding 30 mg S kg-1 significantly reduced the Cd concentrations in brown rice by 31.1-56.3%, and the Cd concentrations decreased with increasing amount of irrigation water. Similar reductions in Cd concentrations in rice shoots and rice straw collected at tillering and maturity stages were observed after application of SVI. However, the effect of S0 application on Cd accumulation in grain was not significant under different water regimes. Furthermore, this study found that application of both SVI and S0 inhibited the transfer of Cd from rice roots to shoots in most cases. These findings indicate that replacing traditional fertilizers with SO42--containing fertilizers, especially combined with increased irrigation, could be a potential approach to mitigate Cd accumulation in rice growing in Cd-contaminated acidic paddy soils.

7.
Int J Oncol ; 56(2): 606-617, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894296

RESUMO

Abnormal metabolism serves a critical role in the development and progression of different types of malignancies including glioblastoma (GBM), and may therefore serve as a promising target for treatment of cancer. Preclinical studies have indicated that a ketogenic diet (KD) may exhibit beneficial effects in patients with GBM; however, the underlying mechanisms remain incompletely understood. The aim of the present study was to evaluate the effects of a KD on glioma stem­like cells (GSCs), by culturing patient­derived primary GSCs as well as a GSC cell line in glucose­restricted, ß­hydroxybutyrate­containing medium (BHB­Glow) which was used to mimic clinical KD treatment. GSCs cultured in BHB­Glow medium exhibited reduced proliferation and increased apoptosis compared with cells grown in the control medium. Furthermore, decreased expression of stem cell markers, diminished self­renewal in vitro, and reduced tumorigenic capacity in vivo, providing evidence that the stemness of GSCs was compromised. Mechanistically, culturing in BHB­Glow medium reduced glucose uptake and inhibited glycolysis in GSCs. Furthermore, culturing in the BHB­Glow medium resulted in morphological and functional disturbances to the mitochondria of GSCs. These metabolic changes may have reduced ATP production, promoted lactic acid accumulation, and thus, increased the production of reactive oxygen species (ROS) in GSCs. The expression levels and activation of mammalian target of rapamycin, hypoxia­inducible factor 1 and B­cell lymphoma 2 were decreased, consistent with the reduced proliferation of GSCs in BHB­Glow medium. ROS scavenging reversed the inhibitory effects of a KD on GSCs. Taken together, the results demonstrate that treatment with KD inhibited proliferation of GSCs, increased apoptosis and attenuated the stemness in GSCs by increasing ROS production.

8.
Cell Death Dis ; 11(1): 6, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31919341

RESUMO

Aflatoxin B1 (AFB1) is a potent hepatocarcinogen in humans and exposure to AFB1 is known to cause both acute and chronic hepatocellular injury. As the liver is known to be the main target organ of aflatoxin, it is important to identify the key molecules that participate in AFB1-induced hepatotoxicity and to investigate their underlying mechanisms. In this study, the critical role of caveolin-1 in AFB1-induced hepatic cell apoptosis was examined. We found a decrease in cell viability and an increase in oxidation and apoptosis in human hepatocyte L02 cells after AFB1 exposure. In addition, the intracellular expression of caveolin-1 was increased in response to AFB1 treatment. Downregulation of caveolin-1 significantly alleviated AFB1-induced apoptosis and decreased cell viability, whereas overexpression of caveolin-1 reversed these effects. Further functional analysis showed that caveolin-1 participates in AFB1-induced oxidative stress through its interaction with Nrf2, leading to the downregulation of cellular antioxidant enzymes and the promotion of oxidative stress-induced apoptosis. In addition, caveolin-1 was found to regulate AFB1-induced autophagy. This finding was supported by the effect that caveolin-1 deficiency promoted autophagy after AFB1 treatment, leading to the inhibition of apoptosis, whereas overexpression of caveolin-1 inhibited autophagy and accelerated apoptosis. Interestingly, further investigation showed that caveolin-1 participates in AFB1-induced autophagy by regulating the EGFR/PI3K-AKT/mTOR signaling pathway. Taken together, our data reveal that caveolin-1 plays a crucial role in AFB1-induced hepatic cell apoptosis via the regulation of oxidation and autophagy, which provides a potential target for the development of novel treatments to combat AFB1 hepatotoxicity.

9.
Science ; 367(6476): 440-445, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31974254

RESUMO

The arousal state of the brain covaries with the motor state of the animal. How these state changes are coordinated remains unclear. We discovered that sleep-wake brain states and motor behaviors are coregulated by shared neurons in the substantia nigra pars reticulata (SNr). Analysis of mouse home-cage behavior identified four states with different levels of brain arousal and motor activity: locomotion, nonlocomotor movement, quiet wakefulness, and sleep; transitions occurred not randomly but primarily between neighboring states. The glutamic acid decarboxylase 2 but not the parvalbumin subset of SNr γ-aminobutyric acid (GABA)-releasing (GABAergic) neurons was preferentially active in states of low motor activity and arousal. Their activation or inactivation biased the direction of natural behavioral transitions and promoted or suppressed sleep, respectively. These GABAergic neurons integrate wide-ranging inputs and innervate multiple arousal-promoting and motor-control circuits through extensive collateral projections.

10.
Oncogene ; 39(8): 1807-1820, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31740785

RESUMO

Increasing evidence has suggested that liver cancer arises partially from transformed hepatic progenitor cells (HPCs). However, the detailed mechanisms underlying HPC transformation are poorly understood. In this study, we provide evidence linking the coexistence of hepatitis B virus X protein (HBx) and transforming growth factor beta 1 (TGF-ß1) with miR-199a-3p in the malignant transformation of HPCs. The examination of liver cancer specimens demonstrated that HBx and TGF-ß1 expression was positively correlated with epithelial cell adhesion molecule (EpCAM) and cluster of differentiation 90 (CD90). Importantly, EpCAM and CD90 expression was much higher in the specimens expressing both high HBx and high TGF-ß1 than in those with high HBx or high TGF-ß1 and the double-low-expression group. HBx and TGF-ß1 double-high expression was significantly associated with poor prognosis in primary liver cancer. We also found that HBx and TGF-ß1 induced the transformation of HPCs into hepatic cancer stem cells and promoted epithelial-mesenchymal transformation, which was further enhanced by concomitant HBx and TGF-ß1 exposure. Moreover, activation of the c-Jun N-terminal kinase (JNK)/c-Jun pathway was involved in the malignant transformation of HPCs. miR-199a-3p was identified as a significantly upregulated microRNA in HPCs upon HBx and TGF-ß1 exposure, which were shown to promote miR-199a-3p expression via c-Jun-mediated activation. Finally, we found that miR-199a-3p was responsible for the malignant transformation of HPCs. In conclusion, our results provide evidence that TGF-ß1 cooperates with HBx to promote the malignant transformation of HPCs through a JNK/c-Jun/miR-199a-3p-dependent pathway. This may open new avenues for therapeutic interventions targeting the malignant transformation of HPCs in treating liver cancer.

11.
Rapid Commun Mass Spectrom ; 34(4): e8591, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-31729085

RESUMO

RATIONALE: Accurate quantitative analysis of bromine and iodine in serum is an important aspect of monitoring body condition, but the volatile loss of halogen in sample pretreatment is a troublesome problem. We present a validated and flexible high-throughput method for quantification of bromine and iodine in dried serum spots (DSS) using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and an external aqueous standard calibration curve. The influence of serum matrix and laser ablation (LA) conditions on the analysis of bromine and iodine in DSS was researched systematically. METHODS: Aqueous standards without matrix matching were used for calibration to analyze bromine and iodine in serum by LA-ICP-MS. 5-µL volumes of the aqueous standard solution and serum samples in 10 times diluted concentration were deposited on the PTFE paper to form dried standard calibration spots (DSCS) and DSS, of less than 2 mm in diameter. LA was performed using a focused Nd:YAG laser beam in raster lineal scan mode. RESULTS: The limits of detection (LODs) for bromine and iodine in DSS were 0.23 and 0.03 mg L-1 , respectively. The relative standard deviation (RSD) for this method was less than 10%. The samples were also detected with matrix matching calibration by ICP-MS. The accuracy of the method was verified by statistical analysis of these results from ICP-MS and LA-ICP-MS. The accuracy is satisfactory with recoveries ranging from 81.5% to 118%. CONCLUSIONS: A novel and simple approach for high-throughput screening of bromine and iodine in DSS has been established by LA-ICP-MS. Calibration could be achieved using an aqueous standard solution instead of a matrix-matching solution. The method allowed analysis of low-volume biological samples without derivatization and decreased the risk of contamination or loss.

12.
J Asian Nat Prod Res ; 22(2): 131-137, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30526062

RESUMO

Nine ursane-type triterpenoids including three new ones 2α, 19α-dihydroxyurs-3-O-acetyltormentic acid (1), 1α, 2α, 3α, 20ß-tetrahydroxyurs -13(18)-en-28-oic acid (2), and 2α, 3α, 20ß, 24-tetrahydroxyurs-13(18)-en-28-oic acid (3) were isolated from the roots of Rosa multiflora. Their structures were elucidated by extensive spectroscopic methods, including NMR, MS, and IR spectroscopic analyses data. All the isolates were evaluated for their anti-inflammatory activity in vitro and the results showed that compounds 1-9 displayed moderate inhibitory activity with IC50 values ranging from 24.7 to 86.2 µM compared with the postitive control Amino guanidine (IC50 4.3 µM).[Formula: see text].


Assuntos
Rosa , Triterpenos , Anti-Inflamatórios , Estrutura Molecular
13.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(10): 944-948, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31814572

RESUMO

T cell adoptive therapy using chimeric antigen receptor T (CAR-T) cells has emerged as a novel strategy for the treatment of cancer. CAR-T cells kill tumor cells independent on the major histocompatibility complex (MHC), which has already achieved impressive progression in the treatment of blood malignancies. Nonetheless, in the treatment of solid tumors, CAR-T cell therapy has problems of easy off-target and inefficient treatment. The rapid development of synthetic biology has greatly enhanced the enthusiasm of CAR-T designers. In this review, we present discussions around current constraints on CAR-T cell therapy in the treatment of solid tumor and cutting-edge progress of new-type CAR-T cell armed with synthetic biology. Moreover, the preclinical studies and clinical trials of several solid tumor targets with a wide range of applications are described in detail.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Imunoterapia Adotiva , Neoplasias/terapia , Receptores de Antígenos Quiméricos , Humanos , Receptores de Antígenos de Linfócitos T
14.
Medicine (Baltimore) ; 98(50): e18362, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852141

RESUMO

BACKGROUND: According to the Barcelona Clinic Liver Cancer (BCLC) staging system, the presence of portal vein tumor thrombosis (PVTT) is considered to indicate an advanced stage of hepatocellular carcinoma (HCC) with nearly no cure. Hepatic resection and transarterial chemoembolization (TACE) have recently been recommended for treatment of HCC with PVTT. METHODS: We conducted a systematic review to compare the overall survival between patients with HCC and PVTT undergoing hepatectomy, TACE or conservative treatment including sorafenib chemotherapy. The PubMed, Web of Science, and Cochrane Library databases were searched. All relevant studies were considered. Hazard ratios with 95% confidence intervals were calculated for comparison of the cumulative overall survival. Ten retrospective studies met the inclusion criteria and were included in the review. RESULTS: Overall survival was not higher in the hepatectomy group than TACE group. But survival rate was higher in hepatectomy group than conservative group. The subgroup analysis demonstrated that hepatectomy was superior in patients without PVTT in the main trunk than in patients with main portal vein invasion. In patients without main PVTT, hepatectomy has showed more benefit than TACE. However, there has been no significant difference between the hepatectomy and TACE groups among patients with main PVTT. CONCLUSION: For patients with resectable HCC and PVTT, hepatectomy might be more effective in patients without PVTT in the main trunk than TACE or conservative treatment.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica/mortalidade , Hepatectomia/mortalidade , Neoplasias Hepáticas , Veia Porta/cirurgia , Sorafenibe/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Tratamento Conservador/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Masculino , Taxa de Sobrevida , Resultado do Tratamento , Trombose Venosa
15.
Cell Death Dis ; 10(12): 869, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31740664

RESUMO

Extracellular vesicles (EVs) including exosomes can serve as mediators of cell-cell communication under physiological and pathological conditions. However, cargo molecules carried by EVs to exert their functions, as well as mechanisms for their regulated release and intake, have been poorly understood. In this study, we examined the effects of endothelial cells-derived EVs on neurons suffering from oxygen-glucose deprivation (OGD), which mimics neuronal ischemia-reperfusion injury in human diseases. In a human umbilical endothelial cell (HUVEC)-neuron coculture assay, we found that HUVECs reduced apoptosis of neurons under OGD, and this effect was compromised by GW4869, a blocker of exosome release. Purified EVs could be internalized by neurons and alleviate neuronal apoptosis under OGD. A miRNA, miR-1290, was highly enriched in HUVECs-derived EVs and was responsible for EV-mediated neuronal protection under OGD. Interestingly, we found that OGD enhanced intake of EVs by neurons cultured in vitro. We examined the expression of several potential receptors for EV intake and found that caveolin-1 (Cav-1) was upregulated in OGD-treated neurons and mice suffering from middle cerebral artery occlusion (MCAO). Knock-down of Cav-1 in neurons reduced EV intake, and canceled EV-mediated neuronal protection under OGD. HUVEC-derived EVs alleviated MCAO-induced neuronal apoptosis in vivo. These findings suggested that ischemia likely upregulates Cav-1 expression in neurons to increase EV intake, which protects neurons by attenuating apoptosis via miR-1290.

16.
Nat Commun ; 10(1): 5277, 2019 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-31754099

RESUMO

Mitochondrial calcium ([Ca2+]mito) dynamics plays vital roles in regulating fundamental cellular and organellar functions including bioenergetics. However, neuronal [Ca2+]mito dynamics in vivo and its regulation by brain activity are largely unknown. By performing two-photon Ca2+ imaging in the primary motor (M1) and visual cortexes (V1) of awake behaving mice, we find that discrete [Ca2+]mito transients occur synchronously over somatic and dendritic mitochondrial network, and couple with cytosolic calcium ([Ca2+]cyto) transients in a probabilistic, rather than deterministic manner. The amplitude, duration, and frequency of [Ca2+]cyto transients constitute important determinants of the coupling, and the coupling fidelity is greatly increased during treadmill running (in M1 neurons) and visual stimulation (in V1 neurons). Moreover, Ca2+/calmodulin kinase II is mechanistically involved in modulating the dynamic coupling process. Thus, activity-dependent dynamic [Ca2+]mito-to-[Ca2+]cyto coupling affords an important mechanism whereby [Ca2+]mito decodes brain activity for the regulation of mitochondrial bioenergetics to meet fluctuating neuronal energy demands as well as for neuronal information processing.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31614944

RESUMO

The present study aims to explore the impact of career development support on job adaptation and withdrawal intention, and the multilevel moderating role of host country environmental factors. Through the questionnaire survey, we collected 242 expatriates' data of 25 countries from China's multinational corporations. Based on the constructed multilevel analysis model, we find: (1) career development support has a significant impact on job adaptation and withdrawal intention of expatriates; (2) job adaptation plays a mediating role between career development support and withdrawal intention; and (3) host country environment plays the multilevel moderating role between career development support and job adaptation. Through the multilevel model of host country environment, this study explores the mechanism of how career development support affects job adaptation and withdrawal intention. The conclusions enhance the understanding of the adaptation of expatriates and have important theoretical and practical reference value to achieve successful expatriate in the context of host country environment.


Assuntos
Satisfação no Emprego , Adulto , Escolha da Profissão , China , Estudos Transversais , Emigrantes e Imigrantes , Emprego , Feminino , Humanos , Intenção , Masculino , Análise Multinível , Inquéritos e Questionários
18.
Biomater Sci ; 7(12): 5404-5413, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31633702

RESUMO

A polyester hernia patch has received extensive attention in mesh hernia repair. However, it is still a challenge to develop polyester-based implants with inherent antibacterial properties due to the lack of active functional groups. In this study, poly(butylene succinate-co-butylene aspartate) (PBSA) was constructed by introducing aspartic acid on a polybutylene succinate (PBS) polyester chain (PBSA). Antimicrobial treatment was conducted by grafting levofloxacin (Lv) on the surface of a PBSA polymer (PBSA-g-Lv). In vitro antibacterial test results showed that PBSA-g-Lv had sufficient local antimicrobiotic effects against Staphylococcus aureus and Escherichia coli and no side effect on L929 cells was observed. Furthermore, almost no change was observed in the thermodynamic properties of PBS and PBSA; in vivo tests demonstrated that this contact-active antibacterial PBSA-g-Lv nanofiber is a promising material to fulfill the dual functions of promoting tissue regeneration and preventing bacterial infection. The presented data confirmed that an antibiotic surface modification of PBSA polyesters was expected to be used as hernia repair materials.

19.
Medicine (Baltimore) ; 98(39): e17180, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574824

RESUMO

BACKGROUND: ATPase family, AAA+ domain containing 2 (ATAD2) is also known as AAA+ nuclear coregulator cancer-associated protein or PRO2000. ATAD2 has been reported as a prognostic factor in different cancer types, but the association between ATAD2 high expression and survival is still unclear. Thereby, this meta-analysis was performed to evaluate the prognostic value of ATAD2 high expression in human cancers. METHODS: All of the studies included were retrieved from PubMed, EMBASE, and Cochrane Library electronic databases. The clinical outcomes were evaluated by calculating hazard ratio (HR) with their 95% confidence interval (CI). RESULTS: Thirteen studies including 2689 patients were eligible for this analysis. The pooled results showed that ATAD2 over-expression was significantly associated with shorter overall survival (OS) (HR = 2.32, 95% CI = 1.77-3.02), as well as shorter recurrence-free survival (RFS), disease-free survival (DFS), and disease-specific survival (DSS) (HR = 1.83, 95% CI = 1.51-2.23) among human cancers. Subgroup analyses for OS were implemented in terms of region, tumor type, and sample size and the results were coincident with overall pooled results. Begg funnel plot and Egger test showed the presence of publication bias for OS. Sensitivity analysis indicated that both results were not affected for removing any study. CONCLUSION: ATAD2 would be likely to act as a prognostic biomarker for the patients of different cancer types and provide a guide on clinical treatment. Prospective clinical studies are needed to support these findings.


Assuntos
ATPases Associadas a Diversas Atividades Celulares/análise , Adenosina Trifosfatases/análise , Proteínas de Ligação a DNA/análise , Neoplasias/enzimologia , Neoplasias/mortalidade , Intervalo Livre de Doença , Humanos , Prognóstico , Modelos de Riscos Proporcionais
20.
Neurochem Res ; 44(11): 2590-2605, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31560103

RESUMO

Increased number of newly-born neurons produced at latent stage after status epilepticus (SE) contribute to aberrant rewiring of hippocampus and are hypothesized to promote epileptogenesis. Although physical training (PT) was reported to cause further increase in neurogenesis after SE, how PT affect their integration pattern is still elusive, whether they integrate into normal circuits or increase aberrant integrations is yet to be determined. To understand this basic mechanism by which PT effects SE and to elaborate the possible role of neuronal integrations in prognosis of SE, we evaluated the effect of 4 weeks of treadmill PT in adult male mice after pilocarpine-induced SE on behavioral and aberrant integrations' parameters. Changes in BDNF gene methylation and its protein level in hippocampus was also measured at latent stage (2-weeks) to explore underlying pathways involved in increasing neurogenesis. Our results demonstrated that although PT increased proliferation and maturation of neurons in dentate gyrus, they showed reduced aberrant integrations into hippocampal circuitry assessed through a decrease in the number of ectopic granular cells, hilar basal dendrites and mossy fiber sprouting as compared to non-exercised SE mice. While SE decreased the percentage methylation of specific CpGs of BDNF gene's promoter, PT did not yield any significant difference in methylation of BDNF CpGs as compared to non-exercised SE mice. In conclusion, PT increases hippocampal neurogenesis through increasing BDNF levels by some pathways other than demethylating BDNF CpGs and causes post SE newly-born neurons to integrate into normal circuits thus resulting in decreased spontaneous recurrent seizures and enhanced spatial memory.


Assuntos
Giro Denteado/metabolismo , Hipocampo/metabolismo , Neurogênese/fisiologia , Condicionamento Físico Animal , Estado Epiléptico/terapia , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proliferação de Células/fisiologia , Ilhas de CpG , DNA/metabolismo , Metilação de DNA , Giro Denteado/patologia , Hipocampo/patologia , Masculino , Camundongos , Neurônios/metabolismo , Neurônios/patologia , Pilocarpina , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/metabolismo , Regulação para Cima
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