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1.
Artigo em Inglês | MEDLINE | ID: mdl-31700131

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

2.
Med Sci Monit ; 25: 8422-8429, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703057

RESUMO

BACKGROUND Herein, we found that tripartite motif-containing 48 (TRIM48) was reduced in human glioblastoma (GBM) cell lines. We investigated whether and how TRIM48 functions in human GBM in vitro. MATERIAL AND METHODS Human GBM cells (U87 MG and U138 MG) were infected with lentivirus to overexpress TRIM48, and 1 human GBM cell line (T98G) was infected with siRNAs to knock down TRIM48 expression. Techniques used included cell proliferation assay, measured by CCK-8 and BrdU-ELISA method, and cell cycle assay, determined using flow cytometry. Curcumin, a specific activator of extracellular signal regulated kinases (ERK1/2), or PD98059, a specific inhibitor of ERK1/2, was used to activate or block the ERK1/2 pathway, respectively. Expression of phosphorylated (p)-ERK1/2, and its downstream targets (Cyclin D1) were measured to assess the mechanism. RESULTS Our data suggest that overexpression of TRIM48 reduces the viability of U87 MG and U138 MG and leads to cell cycle arrest (in G0-G1 phase), which is associated with blockade of the ERK1/2 pathway and reduction of Cyclin D1. In contrast, knockdown of TRIM48 resulted in the opposite effects. Interestingly, the inhibitory effect of TRIM48 overexpression on human GBM cell growth and the inactivation of ERK1/2 were significantly alleviated with additional curcumin treatment, while it the promoted the effect of siTRIM48 on human GBM cell growth, and the activation of ERK1/2 was significantly alleviated with additional PD98059 treatment. CONCLUSIONS TRIM48 suppressed the growth of human GBM cell via the prevention of ERK1/2 activation.

3.
Nat Nanotechnol ; 14(11): 1007-1017, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31695150

RESUMO

Nanomedicines are extensively employed in cancer therapy. We here propose four strategic directions to improve nanomedicine translation and exploitation. (1) Patient stratification has become common practice in oncology drug development. Accordingly, probes and protocols for patient stratification are urgently needed in cancer nanomedicine, to identify individuals suitable for inclusion in clinical trials. (2) Rational drug selection is crucial for clinical and commercial success. Opportunistic choices based on drug availability should be replaced by investments in modular (pro)drug and nanocarrier design. (3) Combination therapies are the mainstay of clinical cancer care. Nanomedicines synergize with pharmacological and physical co-treatments, and should be increasingly integrated in multimodal combination therapy regimens. (4) Immunotherapy is revolutionizing the treatment of cancer. Nanomedicines can modulate the behaviour of myeloid and lymphoid cells, thereby empowering anticancer immunity and immunotherapy efficacy. Alone and especially together, these four directions will fuel and foster the development of successful cancer nanomedicine therapies.

4.
IEEE Trans Cybern ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31581106

RESUMO

In this article, we are concerned with the synchronization problem of Kuramoto oscillators under the sampled-data updating law. This article is motivated by the needs of synchronization of Kuramoto oscillators in the presence of periodic and asynchronous coupling updates. Based on the periodical sampled-data method, a sufficient condition ensuring synchronization under periodic updates is derived. In order to relax the requirement of having all data updated simultaneously, an event-triggered law is designed to implement asynchronous coupling updates. Our synchronization analysis does not rely on any linearization technique around equilibrium points. Instead, we employ the Lyapunov stability theory and nonsmooth analysis technique to deduce the synchronization conditions and estimate the region of attraction. The effectiveness of the proposed sampled-data coupling is illustrated by numerical simulations.

5.
Se Pu ; 37(9): 925-931, 2019 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-31642295

RESUMO

Reproduction is one of the most basic characteristics of organisms, and the guarantee of the continuation and evolution of a species. As the country with world's largest population, China has been gradually increasing its investment in research on the reproductive system in recent years, particularly in the field of basic research. The rapid development and wide application of the microfluidic technology since its birth are sufficient to explain its application prospect. Currently, infertility and birth defects are major problems in the field of reproduction. Micro-reproductive technologies, including microfluidic and organs-on-chips, are formed through the combination of a wide range of basic science and bioengineering technologies. In reproductive research, microfluidic technology display several advantages:flexible design of the microchannel shape and size to better simulate the physiological environment, the low consumption of microfluidic chip, and highly integrated microfluidic technology. Microfluidic technology has been applied to various processes including sperm vitality evaluation and screening, sperm chemotaxis, cumulus oophorus cell removal, zona pellucida removal, ootid localization and screening, fertilization, early embryo culture and reproductive organ simulation. This paper introduces the recent progress in reproductive research based on microfluidic technology and its application prospects.


Assuntos
Microfluídica/tendências , Reprodução , Técnicas Reprodutivas/tendências , Humanos
6.
Cancer Cell ; 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31631026

RESUMO

H3K27M mutations resulting in epigenetic dysfunction are frequently observed in diffuse intrinsic pontine glioma (DIPGs), an incurable pediatric cancer. We conduct a CRISPR screen revealing that knockout of KDM1A encoding lysine-specific demethylase 1 (LSD1) sensitizes DIPG cells to histone deacetylase (HDAC) inhibitors. Consistently, Corin, a bifunctional inhibitor of HDACs and LSD1, potently inhibits DIPG growth in vitro and in xenografts. Mechanistically, Corin increases H3K27me3 levels suppressed by H3K27M histones, and simultaneously increases HDAC-targeted H3K27ac and LSD1-targeted H3K4me1 at differentiation-associated genes. Corin treatment induces cell death, cell-cycle arrest, and a cellular differentiation phenotype and drives transcriptional changes correlating with increased survival time in DIPG patients. These data suggest a strategy for treating DIPG by simultaneously inhibiting LSD1 and HDACs.

7.
IEEE Trans Cybern ; 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31634858

RESUMO

In this article, we consider the distributed synchronization problem of dynamic networked systems with adaptive nonlinear couplings. Based on how the information is collected, the interactions between subsystems are characterized by nonlinear relative state couplings and nonlinear absolute state couplings. In both cases, we show that the considered nonlinear interactions can be used to simulate the couplings with disturbed relative or absolute states. In order to implement the nonlinear couplings in a fully distributed fashion, adaptive control laws are proposed for the adjustment of coupling strengths between connected subsystems. It is shown that the connected network topology is sufficient to ensure the synchronization of dynamic networked systems with the proposed adaptive nonlinear coupling methods. Different from many existing works, the σ-modification technique is used to suppress the increase of the coupling strengths with an additional benefit of preventing the coupling strengths from increasing. Simulation examples are given to assess the performance of the proposed adaptive nonlinear couplings.

8.
Biomark Med ; 13(16): 1417-1427, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31599644

RESUMO

Aim: An existing meta-analysis have investigated the PTX3 levels in systemic lupus erythematosus (SLE) patients, but the number of studies has increased since 2015. We performed an updated meta-analysis to derive a more accurate estimation. Methods: The related literature was systematically searched in PubMed, Embase and The Cochrane Library database (up to 28 February, 2019). Results: SLE patients had significantly higher PTX3 levels than controls (pooled SMD = 0.48; 95% CI: 0.11-0.84). Subgroup analyses indicated SLE patients from non-Caucasian population, with age ≥45 years, SLE disease activity index (SLEDAI) ≥10 and plasma samples had higher PTX3 levels. Conclusion: Circulating PTX3 levels are increased in SLE patients, and affected by age, ethnicity, SLEDAI and sample type.

9.
Int J Clin Pract ; : e13438, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31633263

RESUMO

AIMS: Several studies have reported a potential association between prostate volume (PV) and prostate disease. Here, we classified the risk factors for PV among benign prostatic hyperplasia (BPH) patients. METHODS: In all, 4293 BPH patients with available clinical information were enrolled. Body mass index (BMI) was obtained as weight divided by height squared. PV was calculated as length × width × height (cm) × π/6. Mann-Whitney U tests were used to determine the differences between PV subgroups. Univariate and multiple linear regression tests were performed to uncover the connection between clinical features and PV. The differences in the age, BMI, height and fasting blood glucose (FBG) of the subgroups were evaluated by Kruskal-Wallis tests and adjusted with Bonferroni post hoc correction. A nomogram was created to directly illustrate the mutual interaction of amalgamator parameters. RESULTS: PV did not influence the incidence of kidney stones (P = .815), whereas prostate calculi were positively associated with an enlarged prostate (>30 mL) (P < .001). Age (adjusted R = 0.363, P < .001), height (adjusted R = 0.088, P < .001), BMI (adjusted R = 0.039, P = .013) and FBG (adjusted R = -0.034, P = .027) were the independent risk/protective factors related to enlarged PV among BPH patients. The nomogram illustrated the predictive risk of an enlarged prostate (>30 mL) in men. The area under the ROC curve value was 0.659 in the training cohort and 0.677 in an internal validation cohort. CONCLUSIONS: Age, height and BMI were positive independent risk factors of enlarged PV in BPH patients, and FBG had a protective role.

10.
BMC Genomics ; 20(1): 765, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640544

RESUMO

BACKGROUND: Hypsizygus marmoreus, a high value commercialized edible mushroom is widely cultivated in East Asia, and has become one of the most popular edible mushrooms because of its rich nutritional and medicinal value. Mitochondria are vital organelles, and play various essential roles in eukaryotic cells. RESULTS: In this study, we provide the Hypsizygus marmoreus mitochondrial (mt) genome assembly: the circular sequence is 102,752 bp in size and contains 15 putative protein-coding genes, 2 ribosomal RNAs subunits and 28 tRNAs. We compared the mt genomes of the 27 fungal species in the Pezizomycotina and Basidiomycotina subphyla, with the results revealing that H. marmoreus is a sister to Tricholoma matsutake and the phylogenetic distribution of this fungus based on the mt genome. Phylogenetic analysis shows that Ascomycetes mitochondria started to diverge earlier than that of Basidiomycetes and supported the robustness of the hyper metric tree. The fungal sequences are highly polymorphic and gene order varies significantly in the dikarya data set, suggesting a correlation between the gene order and divergence time in the fungi mt genome. To detect the mt genome variations in H. marmoreus, we analyzed the mtDNA sequences of 48 strains. The phylogeny and variation sited type statistics of H. marmoreus provide clear-cut evidence for the existence of four well-defined cultivations isolated lineages, suggesting female ancestor origin of H. marmoreus. Furthermore, variations on two loci were further identified to be molecular markers for distinguishing the subgroup containing 32 strains of other strains. Fifteen conserved protein-coding genes of mtDNAs were analyzed, with fourteen revealed to be under purifying selection in the examined fungal species, suggesting the rapid evolution was caused by positive selection of this gene. CONCLUSIONS: Our studies have provided new reference mt genomes and comparisons between species and intraspecies with other strains, and provided future perspectives for assessing diversity and origin of H. marmoreus.

12.
J Exp Med ; 216(11): 2546-2561, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31601677

RESUMO

Chronic activation of brain innate immunity is a prominent feature of Alzheimer's disease (AD) and primary tauopathies. However, to what degree innate immunity contributes to neurodegeneration as compared with pathological protein-induced neurotoxicity, and the requirement of a particular glial cell type in neurodegeneration, are still unclear. Here we demonstrate that microglia-mediated damage, rather than pathological tau-induced direct neurotoxicity, is the leading force driving neurodegeneration in a tauopathy mouse model. Importantly, the progression of ptau pathology is also driven by microglia. In addition, we found that APOE, the strongest genetic risk factor for AD, regulates neurodegeneration predominantly by modulating microglial activation, although a minor role of apoE in regulating ptau and insoluble tau formation independent of its immunomodulatory function was also identified. Our results suggest that therapeutic strategies targeting microglia may represent an effective approach to prevent disease progression in the setting of tauopathy.

13.
Eur J Med Chem ; 185: 111729, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31655431

RESUMO

Panaxatriol (PT) is a natural product derived from ginseng that possesses cardioprotective effects in isolated rat hearts. To develop more potent therapeutic agents against myocardial ischemia/reperfusion (MI/R) injury from natural products, a novel series of heterocycle ring-fused panaxatriol derivatives were designed and synthesized. In vitro results showed that approximately half of them exhibited increased cytoprotective activity compared with PT in a cardiomyocyte model of oxygen-glucose deprivation and reperfusion (OGD/R) injury. Furthermore, the in vitro activity of the representative derivative, compound 18, was also confirmed in a rat model of MI/R injury. In vivo results showed that 18 can markedly reduce myocardial infarction size, decrease circulating cardiac troponin I (cTnI) leakage, and alleviate cardiac tissue damage in the rats. Therefore, these findings provide the basis for further development of novel anti-MI/R injury agents.

15.
J Cell Mol Med ; 23(11): 7143-7150, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31475453

RESUMO

Infectious diseases are a type of disease caused by pathogenic microorganisms. Although the discovery of antibiotics changed the treatment of infectious diseases and reduced the mortality of bacterial infections, resistant bacterial strains have emerged. Anti-infective therapy based on aetiological evidence is the gold standard for clinical treatment, but the time lag and low positive culture rate of traditional methods of pathogen diagnosis leads to relative difficulty in obtaining the evidence of pathogens. Compared with traditional methods of pathogenic diagnosis, next-generation and third-generation sequencing technologies have many advantages in the detection of pathogenic microorganisms. In this review, we mainly introduce recent progress in research on pathogenic diagnostic technology and the applications of sequencing technology in the diagnosis of pathogenic microorganisms. This review provides new insights into the application of sequencing technology in the clinical diagnosis of microorganisms.

16.
Sci Total Environ ; 697: 134073, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31473547

RESUMO

The improvement of urban river revetment soil is conducive to promote the growth of pioneer plants which can accelerate the restoration of ecosystems. How to effectively amend soil structure and composition to provide a suitable soil rhizosphere for rapid plant expansion is essential to be solved in the study. Biochar and lake dredged sediments were used to amend an urban river bank soil, where compaction and lack of mineral nutrition hindered the growth of Phragmites. The study found that the addition of 50% mass of dredged sediments combined with 5% mass of straw biochar increased the plant height maximum growth rate, tiller number per unit area, and root biomass by 32.93%, 29.62%, and 41.39%, respectively. The reason for these positive effects on plant growth mainly involved the improvement of rhizosphere soil properties. Addition of biochar increased porosity and available phosphorus content while dredged sediments increased soil organic carbon, thereby increasing the underground unit total phosphorus content of Phragmites by 18.18%. An increase of the Alpha diversity index of rhizosphere microorganisms (8.18%) and the decrease in infection rate of arbuscular mycorrhizal fungi (23.61%) also proved that the rapid expansion of Phragmites was improved owing to changes of the soil physicochemical properties. The combination of biochar and dredged sediments realized synergistic improvement of soil physical structure and increase of nutrient content, which helped promote the growth and expansion of the underground part of Phragmites. This cost-effective method can be feasible used for improvement of urban river revetment ecosystem.

17.
Toxicol Lett ; 316: 109-118, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31472180

RESUMO

Lithocholic acid (LCA) is both a secondary bile acid and a vitamin D receptor (VDR) ligand. The VDR is activated by 1,25-dihydroxy vitamin D3 and plays an important role in maintaining integrity of the intestinal mucosal barrier. LCA can also substitute for vitamin D to carry out the in vivo functions of vitamin D. However, it is unclear whether activation of the VDR by LCA affects mucosal barrier function. In the present study, we researched the protective effect of LCA on tumor necrosis factor-alpha (TNF-α)-induced intestinal epithelial barrier dysfunction in Caco-2 cells of the human epithelial intestinal adenocarcinoma cell line. Caco-2 cell monolayers were pretreated with LCA and then exposed to 100 ng/mL TNF-α. The results showed that LCA alleviated the decrease in transepithelial electrical resistance and the increase in FITC-Dextran flux induced by TNF-α. LCA ameliorated the TNF-α-induced decrease in protein expression and distribution of ZO-1, E-cadherin, Occludin, and Claudin-1, which are tight junction markers. Additionally, the LCA treatment effectively counteracted TNF-α-mediated downregulation of silent information regulator 1 (SIRT1), nuclear factor erythroid2-related factor 2 (Nrf2), and heme oxygenase-1, which are related to oxidative stress. Increases in NF-κB p-p65 and p-IκB-α induced by TNF-α were significantly inhibited by LCA. Considering all these, the present study indicates that LCA has a significant protective effect on TNF-α-induced injury of intestinal barrier function through the VDR and suggests that suppressing NF-κB signaling and activating the SIRT1/Nrf2 pathway might be one of the mechanisms underlying the protective effect of LCA.


Assuntos
Células Epiteliais/efeitos dos fármacos , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Ácido Litocólico/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Receptores de Calcitriol/agonistas , Sirtuína 1/metabolismo , Fator de Necrose Tumoral alfa/toxicidade , Células CACO-2 , Citoproteção , Impedância Elétrica , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Permeabilidade , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Junções Íntimas/patologia
18.
Gen Comp Endocrinol ; 284: 113268, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31491376

RESUMO

CPFX is a highly effective antibiotic, but it has been reported to significantly impair both testicular function and structure in rats. In this study, we assessed reversal of CPFX-induced variation in mice testicular structure and testosterone synthesis by probiotic microbes in the infected model and normal model. We detected testicular weight, testicular structure and Leydig cell variables in numbers. We detected the levels of serum testosterone and steroidogenic enzymes, as well as DBC1, Sirt1, NF-κB, and related redox state and inflammatory response in the testes. The results showed that probiotic microbes had significantly elevated serum testosterone levels and steroidogenic enzymes, higher Sirt1, anti-oxidative enzymes and anti-inflammatory cytokine expression, and lower NF-κB, DBC1, oxidative damage, pro-inflammatory cytokine expression. The results suggest that the testis-protective, antiinflammatory and antioxidation effects of probiotics largely resulted from its ability to decrease oxidative stress and preserve antioxidant activity by stabilizing antioxidant defense systems, reducing oxidative damage and inflammatory response.

19.
IEEE Trans Cybern ; 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31545764

RESUMO

In this article, we investigate a robust distributed model predictive control (DMPC) scheme for tracking the consensus of linear multiagent systems (MASs) subject to additive disturbances and time-varying communication delays. A terminal constraint set is constructed by the Lyapunov-Razumikhin functional, and a corresponding local controller is designed for each agent. Furthermore, the sufficient conditions ensure that the terminal constraint set is provided in the form of linear matrix inequalities (LMIs). The recursive feasibility of the proposed algorithm is guaranteed based on the designed terminal constraint set, terminal cost, and local controller. Moreover, the closed-loop system is shown to be input-to-state stable (ISS). An illustrative example is given to verify the effectiveness of the presented approach.

20.
Arch Oral Biol ; 107: 104494, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31404781

RESUMO

OBJECTIVE: More and more researches focused on studying the relationship of fish consumption with the risk of oral cancer, among which discrepancies have risen. The current study aimed to evaluate the possible relationship about fish consumption and oral cancer risk. METHODS: The PubMed, Web of Science and Chinese National Knowledge Infrastructure were searched up to May 31th, 2019. Pooled odds ratios (OR) and 95% confidence intervals (CI) was calculated using a random-effect model by Stata 12.0 software. RESULTS: A total of 15 publications involving 5211 cases and 70,005 participants were used in the current study. Overall, a significantly reduced association about fish consumption on oral cancer risk was found in all included subjects (OR = 0.74, 95% CI = 0.64-0.85). Subgroup analysis by geographic location suggested that highest category of fish consumption compared with lowest category had an inverse association on oral cancer risk in Europeans only (OR = 0.67, 95% CI = 0.55-0.82), instead of other populations. No publication bias was detected. CONCLUSIONS: In summary, our results indicated that fish consumption may contribute to the lower development of oral cancer in European populations, instead of other populations.

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