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1.
Artigo em Inglês | MEDLINE | ID: mdl-32240363

RESUMO

PURPOSE: Cervical lymph-node (CLN) metastasis commonly occurs in patients with nasopharyngeal carcinoma (NPC) metastasis. The presence of Epstein-Barr virus (EBV) genomes in neck lymph nodes may diagnose CLN. This research was designed to appraise the diagnostic value of EBV concentration for cervical lymph nodes in NPC. METHODS: Two hundred and fifty-three NPC patients with 276 CLNs were enrolled. MRI was performed to detect CLN metastasis, and plasma EBV concentration was measured by quantitative PCR before treatment. Ultrasonography (US) and US-FNA were subsequently performed in the suspicious lymph nodes. Fifteen patients (22 lymph nodes) underwent fine-needle aspiration cytology (FNAC), and the remaining 242 patients (254 lymph nodes) underwent core needle biopsy (CNB) for CLNs at the clinician's demand. The aspiration needle was rinsed with 1 ml of normal saline for EBV detection. The method of lymph-node EBV measurement was consistent with that for plasma. The MRI results and EBV concentrations in plasma and lymph nodes were recorded and analyzed. Plasma EBV concentrations ≥ 4000 copies/ml were regarded as positive. RESULTS: CLN-EBV concentrations ≥ 787.5 copies/ml were regarded as positive according to receiver-operating characteristic curve analysis. The AUC of the EBV (0.925) concentration in CLN metastasis was significantly larger than the AUC of MRI (0.714) (P < 0.001). The sensitivity and specificity were 94.09% and 48.72% for MRI in lymph-node metastasis and 95.36% (P > 0.05) and 84.62% (P < 0.01) for EBV DNA in CLN metastasis, respectively. The sensitivity and specificity of EBV in plasma were 77.2% and 71.8%, respectively. The diagnostic specificity and AUC of EBV in CLNs were higher than those of MRI and plasma EBV (P < 0.005). CONCLUSIONS: Ultrasound-guided CLN FNA to obtain EBV concentrations may provide a new method to diagnose CLN metastasis with high sensitivity and specificity.

2.
J Cell Mol Med ; 24(9): 5082-5096, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32191396

RESUMO

Benign prostatic hyperplasia (BPH) occurs most commonly among older men, often accompanied by chronic tissue inflammation. Although its aetiology remains unclear, autoimmune dysregulation may contribute to BPH. Regulatory T cells (Tregs) prevent autoimmune responses and maintain immune homeostasis. In this study, we aimed to investigate Tregs frequency, phenotype, and function in BPH patients and to evaluate adoptive transfer Tregs for immunotherapy in mice with BPH via CD39. Prostate specimens and peripheral blood from BPH patients were used to investigate Treg subsets, phenotype and Treg-associated cytokine production. Sorted CD39+/- Tregs from healthy mice were adoptively transferred into mice before or after testosterone propionate administration. The Tregs percentage in peripheral blood from BPH patients was attenuated, exhibiting low Foxp3 and CD39 expression with low levels of serum IL-10, IL-35 and TGF-ß. Immunohistochemistry revealed Foxp3+ cells were significantly diminished in BPH prostate with severe inflammatory. Although the Tregs subset was comprised of more effector/memory Tregs, CD39 was still down-regulated on effector/memory Tregs in BPH patients. Before or after testosterone propionate administration, no alterations of BPH symptoms were observed due to CD39- Tregs in mice, however, CD39+ Tregs existed more potency than Tregs to regulate prostatic hyperplasia and inhibit inflammation by decreasing IL-1ß and PSA secretion, and increasing IL-10 and TGF-ß secretion. Furthermore, adoptive transfer with functional Tregs not only improved prostate hyperplasia but also regulated muscle cell proliferation in bladder. Adoptive transfer with Tregs may provide a novel method for the prevention and treatment of BPH clinically.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32215933

RESUMO

The efficacy of dexmedetomidine in the prevention of postoperative delirium (POD) remains ambiguous, however, it has been used to reduce the incidence of delirium in elderly patients. Here, we conducted a meta-analysis study for assessing the effects of dexmedetomidine on POD among elderly patients following non-cardiac surgery. A systematic literature search was performed against the PubMed, EMBASE, Cochrane Library, and Web of Science databases, and all relevant literature published till November 30, 2019, were considered. Our analysis included 16 randomised controlled trials conducted with 4534 patients for exploring the effects of dexmedetomidine on POD in elderly patients following non-cardiac surgery. It was observed that the overall incidence of POD was significantly lower in the dexmedetomidine group than in the control group (risk ratio [RR] 0.51, 95% confidence interval [CI] 0.43-0.61, P < .01). Similar results were obtained from subgroup analysis upon comparison of the placebo (RR 0.52, 95% CI 0.41-0.66, P < .01, moderate quality of evidence), propofol-treated (RR 0.55, 95% CI 0.38-0.78, P < .01, low quality of evidence), and midazolam-treated (RR 0.38, 95% CI 0.20-0.71, P < .01, low quality of evidence) groups. Trial sequential analysis revealed that the cumulative z-value superseded the monitoring boundary and reached the required information size. However, patients who received dexmedetomidine had a higher incidence of bradycardia and hypotension. In conclusion, the meta-analysis revealed that dexmedetomidine appears to decrease the risk of POD in elderly patients following non-cardiac surgery. However, as some of the studies were heterogeneous and of low quality, high-quality trials are necessary for drawing more definitive conclusions.

5.
Stem Cells Dev ; 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32178579

RESUMO

Photoreceptor transplantation can rescue the retinal function of late-stage rd1 mice. Many studies have used synaptic markers to suggest that there are synaptic connections after transplantation, but how donor and host cells are connected remains unknown. Many molecules are needed for triad ribbon synapse formation in wild-type mice. Among them, pikachurin is an important extracellular matrix protein that bridges the pre- and postsynaptic components. To investigate the mechanism of the synaptic connection between donor photoreceptor and host retina, we studied the expression of pikachurin in late-stage rd1 mice before and after transplantation. The results showed that the full-length form of pikachurin could still be detected in the degenerated retina. After photoreceptors were transplanted to the subretinal space of rd1 or wild-type mice, pikachurin was detected in the cytoplasm of most donor photoreceptor cells. Pikachurin puncta may represent the cleaved form of the protein and may indicate synapse generation, but it was barely observed in the donor mass of wild-type mice (3.83 ± 3.17 puncta per 100 donor cells). In contrast, pikachurin puncta could be found in the graft of the rd1 mouse retina, but the number was low (21.35 ± 9.48 puncta per 100 donor cells). In addition, 54.12 ± 8.45% of bassoon puncta were paired with pikachurin puncta and 45.5 ± 6.33% were not, indicating that there were fewer pikachurin puncta than bassoon. These results suggest that pikachurin is involved in only a portion of the synaptic connection between the donor photoreceptor and host retina.

6.
Poult Sci ; 99(2): 1096-1106, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32029146

RESUMO

We studied the microbial profiles of the duodenum, jejunum, and ileum during different developmental stages in the duck using high-throughput sequencing of the bacterial 16S rRNA gene. We also investigated the differences in the microbiota in the duodenum, jejunum, and ileum at different developmental times. A correlation analysis was performed between the most abundant bacterial genera and the development of the small intestine. An analysis of alpha diversity indicated different species richness and bacterial diversity in the different small intestinal segments and at different development times. A beta diversity analysis indicated differences in the bacterial community compositions across time. In a weighted UniFrac principal coordinates analysis, the samples clustered into two categories, 2 to 4 wk and 6 to 10 wk, in the duodenum, jejunum, and ileum. Our results show that the small intestine is predominantly populated by the phyla Firmicutes, Bacteroidetes, and Proteobacteria throughout the developmental stages of the duck. The duodenum, jejunum, and ileum shared most of the bacterial phyla and genera present, although they showed significant differences in their relative abundances in the intestinal segments and developmental stages. They shared different bacterial taxa during development times and among different segments when the intergroup differences were analyzed. The genera Bacillus, Corynebacterium 1, Lactococcus, Sphingomonas, and Haliangium correlated moderately positively with the increase in bodyweight and the lengths and weights of the duodenum, jejunum, and ileum, and these genera may be considered important markers when assessing the heath of the intestinal microbiota in ducks. This study provides a foundation upon which to extend our knowledge of the diversity and composition of the duck microbiota and a basis for further studies of the management of the small intestinal microbiota and improvements in the health and production of ducks.

7.
Sci Rep ; 10(1): 2440, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32051470

RESUMO

The effects of quercetin liposomes (Q-PEGL) on streptozotocin (STZ)-induced diabetic nephropathy (DN) was investigated in rats. Male Sprague Dawley rats were used to establish a STZ induced DN model. DN rats randomly received one of the following treatments for 8 weeks: blank treatment (DN), free quercetin (Que), pegylated liposomes (PEGL) and pegylated quercetin liposomes (Q-PEGL). A group of healthy rats served as the normal control. The fasting blood glucose (FBG), body weights (BWs), renal hypertrophy index (rHI), serum and urine biochemistry, renal histopathology, oxidative stress and immunohistochemical measurements of AGEs were analyzed to compare the effect of different treatments. Que and Q-PEGL significantly improved DN biochemistry and pathological changes, although the treated rats still had some symptoms of DN. The therapeutic effect of Q-PEGL surpassed that of Que. Pegylated quercetin liposomes allow maintaining higher quercetin concentrations in plasma than non-encapsulated quercetin. In conclusion the use of quercetin liposomes allows to reduce disease symptoms in a rat model of DN.

8.
Int Immunopharmacol ; 81: 106271, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32062071

RESUMO

Glaucocalyxin A (GLA) is a bioactive ent-kauranoid diterpenoid derived from the herbal medicine, Rabdosia japonica var. glaucocalyx, and it has been reported to possess marked anti-inflammatory properties. However, the underlying mechanisms are not fully understood. Here, we reported that GLA dramatically inhibited canonical and non-canonical NLRP3 inflammasome activation induced by multiple agonists. In addition, GLA also blocked NLRC4 inflammasome activation but had no effect on AIM2 inflammasome. Furthermore, we found that GLA inhibited NLRP3 or NLRC4 agonists-induced ASC oligomerization, which is an upstream event of the inflammasomes assembly. Most importantly, administration of GLA significantly reduced lipopolysaccharide (LPS)-induced mortality in septic-shock mouse model. Additionally, GLA dose-dependently inhibited the production of interleukin (IL)-1ß, but had no effect on NLRP3-independent TNF-α production induced by LPS in vivo. In conclusion, our study suggests that GLA alleviates LPS-induced septic shock and inflammation via inhibiting NLRP3 inflammasome activation and provides a promising candidate drug for the treatment of NLRP3-driven diseases.

9.
Biol Psychiatry ; 87(8): 756-769, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31955914

RESUMO

BACKGROUND: Synaptic protein dyshomeostasis and functional loss is an early invariant feature of Alzheimer's disease (AD), yet the unifying etiological pathway remains largely unknown. Knowing that cyclin-dependent kinase 5 (CDK5) plays critical roles in synaptic formation and degeneration, its phosphorylation targets were reexamined in search of candidates with direct global impacts on synaptic protein dynamics, and the associated regulatory network was also analyzed. METHODS: Quantitative phosphoproteomics and bioinformatics analyses were performed to identify top-ranked candidates. A series of biochemical assays was used to investigate the associated regulatory signaling networks. Histological, electrochemical, and behavioral assays were performed in conditional knockout, small hairpin RNA-mediated knockdown, and AD-related mice models to evaluate the relevance of CDK5 to synaptic homeostasis and functions. RESULTS: Among candidates with known implications in synaptic modulations, BAG3 ranked the highest. CDK5-mediated phosphorylation on S297/S291 (mouse/human) destabilized BAG3. Loss of BAG3 unleashed the selective protein degradative function of the HSP70 machinery. In neurons, this resulted in enhanced degradation of a number of glutamatergic synaptic proteins. Conditional neuronal knockout of Bag3 in vivo led to impairment of learning and memory functions. In human AD and related mouse models, aberrant CDK5-mediated loss of BAG3 yielded similar effects on synaptic homeostasis. Detrimental effects of BAG3 loss on learning and memory functions were confirmed in these mice, and such effects were reversed by ectopic BAG3 reexpression. CONCLUSIONS: Our results highlight that the neuronal CDK5-BAG3-HSP70 signaling axis plays a critical role in modulating synaptic homeostasis. Dysregulation of the signaling pathway directly contributes to synaptic dysfunction and AD pathogenesis.

10.
Eur J Pharmacol ; 868: 172880, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31863767

RESUMO

Neuropathic pain is a severe disease caused by lesions or diseases in the somatosensory system. Long non-coding RNAs (lncRNAs) are important in the development and maintenance of neuropathic pain. However, the precise role of lncRNAs in regulating neuropathic pain remains largely unknown. In this study, a rat model of bilateral chronic constriction injury (bCCI) was established, and microarray was applied to analyze differentially expressed lncRNAs among sham group, bCCI group and the experimental group (bCCI rats administrated with a specific STAT3 inhibitor WP1066). Linc00311 and lncRNA-AK141205 were uncharacterized lncRNAs both upregulated by > 2 folds in bCCI model compared with Sham group, and they were downregulated by > 2 folds following WP1066 administration compared with bCCI group. Downregulation of linc00311 and lncRNA-AK141205 by specific siRNAs significantly attenuated mechanical allodynia, thermal and cold hyperalgesia in bCCI rats. In addition, inhibition of linc00311 and lncRNA-AK141205 inactivated the signal transducer and activator of transcription 3 (STAT3) signaling in spinal microglia in vivo and in vitro. Inhibition of linc00311 and lncRNA-AK141205 could reduce activation of STAT3 and production of proinflammatory cytokines. Moreover, activating STAT3 with SD19 could antagonize the effect of the suppressive effect of siRNAs on production of proinflammatory cytokines. Hence, it is likely that silencing linc00311 and lncRNA-AK141205 may be a promising and novel treatment for neuropathic pain.

11.
Plant Biotechnol J ; 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31733093

RESUMO

Kernel size is an important trait determining cereal yields. In this study, we cloned and characterized TaDA1, a conserved negative regulator of kernel size in wheat (Triticum aestivum). The overexpression of TaDA1 decreased the size and weight of wheat kernels, while its down-regulation using RNA interference (RNAi) had the opposite effect. Three TaDA1-A haplotypes were identified in Chinese wheat core collections, and a haplotype association analysis showed that TaDA1-A-HapI was significantly correlated with the production of larger kernels and higher kernel weights in modern Chinese cultivars. The haplotype effect resulted from a difference in TaDA1-A expression levels between genotypes, with TaDA1-A-HapI resulting in lower TaDA1-A expression levels. This favourable haplotype was found having been positively selected during wheat breeding over the last century. Furthermore, we demonstrated that TaDA1-A physically interacts with TaGW2-B. The additive effects of TaDA1-A and TaGW2-B on kernel weight were confirmed not only by the phenotypic enhancement arising from the simultaneous down-regulation of TaDA1 and TaGW2 expression, but also by the combinational haplotype effects estimated from multi-environment field data from 348 wheat cultivars. A comparative proteome analysis of developing transgenic and wild-type grains indicated that TaDA1 and TaGW2 are involved in partially overlapping but relatively independent protein regulatory networks. Thus, we have identified an important gene controlling kernel size in wheat and determined its interaction with other genes regulating kernel weight, which could have beneficial applications in wheat breeding.

12.
Chem Biodivers ; 16(12): e1900514, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31609067

RESUMO

Coreopsis tinctoria capitula (CTC) of the Compositae family has been used traditionally to treat various diseases in China, particularly type 2 diabetes mellitus (T2DM). This study evaluated the anti-lipid peroxidation, α-glucosidase and α-amylase inhibitory effects of CTC extracts, and analyzed its chemical composition by HPLC. Moreover, the antioxidant activity and protection effects of CTC extracts were investigated on high-fat/high-sugar and streptozotocin-induced T2DM mice. In vitro study, the ethyl acetate extract (EAE) and butanol extract (BE) of CTC exhibited anti-lipid peroxidation (IC50 : BHA>BE or EAE>ascorbic acid, p<0.05) and α-glucosidase inhibitory activity (IC50 : BE>EAE, p<0.05). In vivo, the BE at the dose of 600 mg/kg was intragastrically given to T2DM mice, which exhibited a certain extent of repair and improvement of the levels of CAT, GSH, GSH-PX , SOD, as well as plasma biomarkers, compared with those in the model group (p<0.05). These results demonstrated that CTC extracts have a positive effect to treat T2DM and it can be used for the treatment of T2DM in the future.


Assuntos
Coreopsis/química , Diabetes Mellitus Experimental/patologia , Dieta Hiperlipídica , Extratos Vegetais/química , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases/química , Animais , Antioxidantes/química , Antioxidantes/metabolismo , Biomarcadores/sangue , Coreopsis/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/prevenção & controle , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Flores/química , Flores/metabolismo , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Rim/efeitos dos fármacos , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Camundongos , Estreptozocina/toxicidade , alfa-Amilases/metabolismo , alfa-Glucosidases/metabolismo
13.
J Mater Chem B ; 7(40): 6075-6086, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31389470

RESUMO

The residual tumor cells after chemotherapy, even in very small numbers, are generally drug-resistant and invasive, which might result in the progress of tumor metastasis and recurrence. In this research, a new combination chemotherapy strategy of salinomycin (SL) that could selectively inhibit multidrug-resistant tumor cells and a traditional broad-spectrum antitumor drug, doxorubicin (DOX), based on redox-degradable nano-micelles was developed to overcome drug resistance in vitro. The results in vitro indicated that DOX + SL co-loaded nano-micelles could not only escape from the drug efflux of adriamycin-resistant MCF-7 cells (A/MCF-7) but also penetrated and infiltrated into 3D-cultured MCF-7 and 4T1 tumor spheres in vitro more effectively, resulting in a strong antiproliferative effect. In the allogeneic metastatic 4T1 tumor model, the combination chemotherapy of DOX + SL encapsulated in nano-micelles effectively suppressed tumor growth with no splenomegaly and no other major tissue damage, and reversed the EMT progress, and inhibited tumor recurrence and metastasis more effectively after drug withdrawal.

14.
Int Wound J ; 16(5): 1206-1213, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31418529

RESUMO

To assess the efficacy and safety of dexmedetomidine (DEX) as an adjuvant to local wound infiltration anaesthesia in abdominal surgery, we conducted this meta-analysis. First, the systematic search strategy was performed on PubMed, Embase, and Cochrane Library and five randomised controlled trials (RCTs) involving 294 patients were included. Then, the outcome data were extracted from the studies and their effect sizes were calculated using Review Manager 5. As a result, the addition of DEX significantly reduced visual analogy scores at 6 hours after surgery (mean difference = -0.53[-0.82, -0.25], P < .001), 12 hours after surgery (mean difference = -0.39 [-0.73, -0.05]; P = .03), and 24 hours after surgery (mean difference = -0.20 [-0.29, -0.11], P < .001) and reduced total analgesic consumption within 24 hours after surgery (mean difference = -4.92 [-9.00, -0.84]; P = .02) compared with placebo groups. However, there was no difference in the incidence of postoperative nausea and vomiting (risk ratio = 0.68 [0.41, 1.14]; P = .14). In summary, DEX as a local anaesthetic adjuvant added for local wound infiltration anaesthesia in abdominal surgery could reduce visual analogy scores and postoperative analgesic consumption without changing incidence of postoperative nausea and vomiting.

15.
J Diabetes Res ; 2019: 9626413, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467930

RESUMO

Objectives: This study is aimed at gaining insights on the changing prevalence, economic burden, and catastrophic costs of diabetes in rural southwest China. Materials and Methods: Data were collected from two cross-sectional health interviews and examination surveys among individuals aged ≥ 35 years in rural Yunnan Province. A prevalence-based cost-of-illness method was used to estimate the cost of diabetes. Information about the participants' demographic characteristics and economic consequences of diabetes was obtained using a standard questionnaire. Fasting blood sugar levels were recorded for each study participant. Results: During the study period, the overall prevalence of diabetes increased from 7.7% to 9.5% (P < 0.01) and the economic cost of diabetes increased 1.52-fold. The largest increases were observed in hospital costs (1.77-fold increase), while unit medication costs fell by 18.6%. Both in 2009 and in 2016, males had higher overall direct and indirect costs of diabetes than females (P < 0.05). Direct costs represented the largest component of economic cost of diabetes while hospital costs were the main drivers of direct medical expenditures, accounting for 66.2% of the total direct costs in 2009 and 75.9% in 2016. The incidence of household catastrophic health payment and household impoverishment due to diabetes was 24.0% and 17.9% in 2009 and 23.6% and 17.6% in 2016, respectively. These rates did not differ between the two survey years (P > 0.05). Conclusions: The prevalence and economic burden of diabetes increased substantially from 2009 to 2016 in rural southwest China. The findings underscore an urgent need for the government to invest more financial resources in the prevention of diabetes and improvement of access to affordable medication in rural southwest China.


Assuntos
Efeitos Psicossociais da Doença , Diabetes Mellitus Tipo 2/economia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/terapia , Gastos em Saúde/tendências , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Saúde da População Rural/economia , Saúde da População Rural/estatística & dados numéricos , Saúde da População Rural/tendências , População Rural/estatística & dados numéricos , Fatores Socioeconômicos , Inquéritos e Questionários
16.
J Exp Clin Cancer Res ; 38(1): 286, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31272499

RESUMO

BACKGROUND: CDK5, an atypical member of the CDK family, play a significant role in the tumorigenesis of multiple organ, but CDK5 and its substrates in genesis and development of HCC is still unclear. METHODS: Expression of CDK5 in HCC tumor and paired adjacent noncancerous tissues from 90 patients were measured by Western blotting, immunohistochemistry, and real-time PCR. The role of CDK5 in cell function and tumorigenesis was explored in HCC cell lines, ex vivo xenografts and diethylnitrosamine induced HCC model. Furthermore, comparative phosphoproteomic screening identified the oncoprotein TPX2 as a new substrate of CDK5. We also identified the effect of CDK5/P25 interaction blocker tamoxifen on HCC cell growth and migration. RESULTS: CDK5 was increased in HCC tisues and the level of CDK5 was correlated with the severity of HCC based on patient recurrence and 5-year fatality rate. Exogenously expressed CDK5 but not kinase-dead CDK5 promoted proliferation, migration, and invasion of HCC cells. Functional ablation of CDK5 significantly inhibited the exacerbation of HCC cells. Xenograft implantation of HCC cells overexpressing CDK5 promoted tumorigenesis, and genetic knockdown of CDK5 reduced HCC growth and metastasis in vivo. More importantly, heterozygous knockout CDK5 (Cdk5+/-) attenuated HCC tumorigenesis induced by diethylnitrosamine. CDK5-mediated phosphorylation of TPX2 at serine 486 promoted its protein stability. TPX2 silence could restore HCC cell migration capability with overexpression CDK5. Treatment with tamoxifen inhibited cell growth and migration of HCC, demonstrating the role of active CDK5 in HCC. CONCLUSIONS: Our results suggest activation of CDK5 is associated with HCC tumorigenesis. CDK5-mediated phosphorylation and stabilization of TPX2 promotes hepatocellular proliferation and tumorigenicity.


Assuntos
Carcinoma Hepatocelular/metabolismo , Proteínas de Ciclo Celular/metabolismo , Quinase 5 Dependente de Ciclina/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Células Hep G2 , Xenoenxertos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas Experimentais/genética , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Nus , Fosforilação
17.
Front Physiol ; 10: 819, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31316397

RESUMO

Divalent metal transporter 1 (DMT1) is a key transporter of iron uptake and delivering in human and animals. However, post-transcriptional regulation of DMT1 is poorly understood. In this study, bioinformatic algorithms (TargetScan, PITA, miRanda, and miRDB) were applied to predict, screen, analyze, and obtain microRNA-16 family members (miR-16, miR-195, miR-497, and miR-15b) targeting DMT1, seed sequence and their binding sites within DMT1 3' untranslated region (3' UTR) region. As demonstrated by dual-luciferase reporter assays, luciferase activity of DMT1 3' UTR reporter was impaired/enhanced when microRNA-16 family member over-expression plasmid/its inhibitor was transfected to HCT116 cells. Corroboratively, co-transfection of microRNA-16 family member over-expression plasmid and DMT1 3' UTR mutant reporter repressed the luciferase activity in HCT116 cells. In addition, over-expression microRNA-16 family member augmented its expression and diminished DMT1 protein expression in HCT116 cells. Interestingly, tail vein injection of miR-16 assay revealed reduced plasma iron levels, higher miR-16 expression, and lower DMT1 protein expression in the duodenum of mice. Taken together, we provide evidence that microRNA-16 family (miR-16, miR-195, miR-497, and miR-15b) is confirmed to repress intestinal DMT1 expression in vitro and in vivo, which will give valuable insight into post-transcriptional regulation of DMT1.

18.
Cancer Biol Ther ; 20(10): 1319-1327, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31311407

RESUMO

Limited studies are available on the molecular pathogenesis of Epstein-Barr virus (EBV)-associated T or natural killer (NK) cell lymphoproliferative disorders (EBV+T/NK-LPD). In this retrospective study, we aim to elucidate the mutation profile of EBV+T/NK-LPD using capture-based targeted sequencing with a panel consisting of 64 lymphoma-related genes to identify driver genes associated with the development of EBV+T/NK-LPD. Targeted sequencing of 169 EBV+T/NK-LPD cases was performed using a panel of 64 lymphoma-related genes. Of the 169 EBV+T/NK-LPD cases, 123 had extra-nodal NK/T-cell lymphoma (ENKTL), 12 had aggressive NK-cell leukemia (ANKL) and 34 had EBV+ T-cell lymphoma of childhood (EBV+TL). The mutation profile revealed that all three subtypes of EBV+T/NK-LPDs had high mutation rates in STAT3, KMT2D, DDX3X, NOTCH1 and TET2. Target sequencing revealed that ENKTL, ANKL and EBV+TL were molecularly distinct, the mutation in nasal-ENKTL and extra-nasal-ENKTL are also different. Survival analysis revealed that ENKTL patients with gene mutations or loss of protein expression in either KMT2D or TET2 were significantly correlated with shorter overall survival. And although the EBV+TL and ANKL groups were too small to confirm survival disadvantage, the adverse prognosis trends of KMT2D or TET2 were showed in these two groups. We conclude that EBV+T/NK lymphoproliferative disorders have very distinct molecular profiles. Our findings also suggest the likely involvement of KMT2D and TET2 in the development of ENKTL, and possibly EBV+T/NK-LPDs in general.

19.
J Mol Model ; 25(8): 221, 2019 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-31302782

RESUMO

The rare-earth doped silicon-based clusters exhibit remarkable structural, physical, and chemical properties, which make them attractive candidates as building units in designing of cluster-based materials with special optical, electronic, and magnetic properties. The structural, stability, electronic, and magnetic properties of pure silicon Sin + 1 (n = 1-9) and rare-earth doped clusters SinEu (n = 1-9) are investigated using the "stochastic kicking" (SK) global search technique combined with density functional theory (DFT) calculations. It was found that: 1) the ground state structures of pure silicon clusters tend to form compact structures rather than cages with the increase of cluster size; 2) the ground state structures for doped species were found to be additional or substitutional sites, and the rare-earth atoms tend to locate on the surface of the silicon clusters; 3) the average binding energy of the doped clusters increased gradually and exhibited the final phenomenon of saturation with the increase of clusters size. The average binding energy of doped clusters was slightly higher than that of pure silicon clusters of the same size, which indicated that the rare-earth atom encapsulated by silicon enhanced the stability of the silicon clusters to some degree; 4) the doped clusters have strong total magnetic moments, which mainly originated from the contribution of rare-earth atoms, whereas the contribution of silicon atoms were almost negligible. As the cluster size increased, the total magnetic moments of binary mixed clusters tended to be stable.

20.
Front Microbiol ; 10: 1180, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31191496

RESUMO

The mechanisms of adaptive resistance of Escherichia coli to aminoglycosides remain unclear. Our RNA-Seq study found that expression of yhjX was markedly upregulated during initial exposure to subinhibitory concentrations of gentamicin. The expression of yhjX was then downregulated dramatically during a second exposure to gentamicin compared to the first exposure. YhjX encodes a putative transporter of the major facilitator superfamily, which is known to be the sole target of the YpdA/YpdB two-component system, the expression of which is highly and specifically induced by pyruvate. To investigate the effect of yhjX on the adaptive resistance of E. coli, in the present study, we constructed yhjX deletion and complemented strains of E. coli ATCC25922. Changes in extracellular pyruvate levels of wide-type and yhjX mutant were measured to determine whether YhjX functions as a pyruvate transporter. The results showed that yhjX deletion improved the growth of E. coli in medium containing subinhibitory concentrations of gentamicin. The yhjX deletion mutant did not exhibit adaptive resistance to subinhibitory concentrations of gentamicin. YhjX might not function as a pyruvate efflux pump in E. coli but was associated with the decrease following a sharp increase in the extracellular pyruvate level. Our findings indicate that yhjX regulates the growth of E. coli in the presence of a subinhibitory concentration of gentamicin and mediates the adaptive resistance to gentamicin.

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