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1.
Biomed Res Int ; 2020: 4951692, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32149111

RESUMO

Wilms' tumor (WT) is the most common type of childhood kidney cancer, and most cases present with favorable histology and respond well to standard treatment. However, a subset of patients with WT is diagnosed with bilateral, relapsed, and high-risk tumors which remain the leading cause of cancer-related death in children. Long noncoding RNAs (lncRNAs) and their aberrant expression have currently been attracting great attention as oncogenes or tumor suppressors during tumor initiation and progression. So far, their roles and related competitive endogenous RNA (ceRNA) network remain unelucidated in nephroblastoma pathogenesis. We comprehensively integrated lncRNA, microRNA (miRNA), and messenger RNA (mRNA) expression profiles from the Therapeutically Applicable Research to Generate Effective Treatment (TARGET) database and screened out differentially expressed mRNAs (DEMs), lncRNAs (DELs), and miRNAs (DEMis) to construct a ceRNA network based on the information generated from miRcode, miRTarBase, TargetScan, and miRDB. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to analyze the functional characteristics of DEMs in the ceRNA network. The interaction between protein molecules was also analyzed by establishing a protein-protein interaction network. Finally, prognosis-related biomarkers were identified via survival analysis. Initially, 1647 DELs, 115 DEMis, and 3280 DEMs (|log FC| > 2; FDR < 0.01) were obtained using the R package. Next, we constructed a lncRNA-miRNA-mRNA network (ceRNA network), in which 176 DELs, 24 DEMis, and 141 DEMs were identified. Furthermore, 148 functional enrichment terms from GO were identified and 29 KEGG pathways were found to be significantly enriched. We also integrated patient clinical information to analyze the association between DERNAs and patient prognosis. We found that high expression of 8 DELs (LINC00473, AL445228.2, DENND5B-AS1, DLEU2, AC123595.1, AC135178.1, LINC00535, and LMO7-AS1) and 4 DEMs (CEP55, DEPDC1, PHF19, and TRIM36) correlated with poor survival in a patient with WT, whereas high expression of 2 DELs (MEG3 and RMST), 1 DEM (KIAA0922), and 1 DEMi (hsa-mir-200a) could possibly lead to better clinical outcomes. For the first time, the present study provided a novel insight into lncRNA-related ceRNA networks and identified potential prognostic biomarkers in Wilms' tumor.

2.
Commun Biol ; 3(1): 89, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111943

RESUMO

An unbalanced pigment distribution among the sepal and petal segments results in various colour patterns of orchid flowers. Here, we explored this type of mechanism of colour pattern formation in flowers of the Cattleya hybrid 'KOVA'. Our study showed that pigment accumulation displayed obvious spatiotemporal specificity in the flowers and was likely regulated by three R2R3-MYB transcription factors. Before flowering, RcPAP1 was specifically expressed in the epichile to activate the anthocyanin biosynthesis pathway, which caused substantial cyanin accumulation and resulted in a purple-red colour. After flowering, the expression of RcPAP2 resulted in a low level of cyanin accumulation in the perianths and a pale pink colour, whereas RcPCP1 was expressed only in the hypochile, where it promoted α-carotene and lutein accumulation and resulted in a yellow colour. Additionally, we propose that the spatiotemporal expression of different combinations of AP3- and AGL6-like genes might participate in KOVA flower colour pattern formation.

3.
Neurochem Res ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32125561

RESUMO

Mitochondrial dysfunction is a hallmark of Alzheimer's disease (AD), which may be related to mitophagy failure. Previous reports suggest that treadmill exercise protects against mitochondrial dysfunction in AD. However, few studies have investigated the relationship between mitophagy and mitochondrial adaptation caused by treadmill exercise in AD. The current study aimed to investigate whether exercise-ameliorated AD is associated with changes in mitophagy activity. Both Wild-type and APP/PS1 transgenic mice were divided into sedentary (WTC and ADC) and exercise (WTE and ADE) groups (n = 9 for each group). WTE and ADE mice were subjected to treadmill exercise for 12 weeks, followed by evaluating the effect of treadmill exercise on learning and memory ability, Aß plaques, mitochondrial Aß peptide level, synaptic activity and mitochondrial function. Meanwhile, mitophagy-related proteins PINK1, Parkin, LC3II and P62 were measured in the hippocampal mitochondrial fractions. The results indicated that exercise not only restored learning and memory ability, but also reduced Aß plaque area, mitochondrial Aß peptide level, and increased levels of synaptic markers SYN and GAP43, as well as reversed mitochondrial dysfunction (defective mitochondrial ultrastructure, decreased PGC-1α, TFAM and ATP levels) in APP/PS1 transgenic mice. Moreover, exercise increased mitophagy activity as evidenced by a significant decrease in levels of P62 and PINK1 as well as an increase in levels of LC3II and Parkin in ADE mice. These findings suggest that treadmill exercise can enhance mitophagy activity in the hippocampus, which is efficient in ameliorating pathological phenotypes of APP/PS1 transgenic mice.

4.
Zhen Ci Yan Jiu ; 45(1): 51-6, 2020 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-32144909

RESUMO

OBJECTIVE: To observe the effect of low-frequency electrical acupoint stimulation on gastrointestinal motility in patients undergoing radical gastrectomy, and its impact on regulation of inflammatory response, so as to evaluate its clinical value. METHODS: A total of 177 patients undergoing radical gastrectomy were randomly divided into conventional group (n=43), low-frequency electrical acupoint stimulation (LEAS) group (n=45), fast track surgery (FTS) group (n=46) and FTS+LEAS group (n=43). Patients of the conventional group received conventional treatment (pre-surgical mechanical bowel preparation, post-surgical fasting, and indwelling abdominal drainage tube, etc.). Patients in the LEAS group were treated by low-frequency electrical stimulation at bilateral Zusanli (ST36), Shangjuxu(ST37), Xiajuxu(ST39) and Sanyinjiao(SP6) for 30 min, once daily from 1 day after the operation to first postoperative flatus. FTS group was given fast track surgery treatment, such as preoperative education, preoperative nutritional support, early oral feeding, early removal of abdominal drainage tube, etc. The FTS+LEAS group was given low-frequency electrical acupoint stimulation on the basis of the FTS treatment. Levels of white blood cells (WBC), neutrophils (N), C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) at 1, 3, and 6 d after the operation in the 4 groups were assayed. The first postoperative flatus and defecation time were recorded. RESULTS: After the treatment, the first postoperative flatus and defecation time in the LEAS, FTS and FTS+LEAS groups were significantly shorter than those of the conventional group (P<0.05), and the first flatus time of the FTS+LEAS group was even earlier than that of the FTS group (P<0.05). No significant differences were found among the 3 groups in the postoperative defecation time (P>0.05). The CRP levels in the 4 groups on 3 and 6 d after operation were higher than those on the 1st postoperative day, and the highest level was on 3 d after the operation. Compared with the conventional group, CRP level on 3 d and CRP and IL-6 levels on 3 and 6 d in the LEAS and FTS+LEAS groups were significantly lower (P<0.05). Compared with the LEAS group, the levels of N, CRP on 3 d and the levels of N, CRP, IL-6 on 6 d in the FTS group were significantly increased (P<0.05). Compared with the FTS group, the level of CRP on 3 d and the levels of N, CRP, IL-6 on 6 d in the FTS+LEAS group were significantly decreased (P<0.05). CONCLUSION: FTS combined with LEAS is superior to simple FTS or LEAS treatment in shortening the first flatus and defecation time and promoting the recovery of gastrointestinal motility function in patients undergoing radical gastrectomy, which may be associated with its effect in alleviating postoperative inflammatory responses.


Assuntos
Pontos de Acupuntura , Neoplasias Gástricas , Estimulação Elétrica , Gastrectomia , Motilidade Gastrointestinal , Humanos , Tempo de Internação , Complicações Pós-Operatórias
5.
J Dig Dis ; 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32129564

RESUMO

OBJECTIVE: Some gastrointestinal subepithelial tumors (SETs) have malignant potential and complete resection may be required. However, endoscopic submucosal dissection (ESD) can be a tedious procedure and requires a long and extensive training to master. Devices for endoscopic full-thickness resection (EFTR) are limited and are not widely available. We report here a simpler endoscopic method to resect small SETs using a commercially available endoscopic mucosal resection (EMR) kit and enucleation technique. METHODS: All patients with SET who underwent device-assisted resection at our tertiary care hospital from April 2015 to November 2016 were enrolled in this retrospective study. All procedures were performed by a single expert endoscopist with an advanced endoscopy trainee. A mucosectomy and a limited dissection under mucosa were performed to preserve the mucosa before a device-assisted enucleation of the tumor to facilitate endoscopic closure of the defect closure in all cases. RESULTS: A total of 12 patients aged 38-70 y, of whom six were males, were included. Most of the tumors originated from the muscularis propria and were located at the proximal gastric body. The mean procedural duration was 53 minutes (range 23-91 min). The average size of the lesions was 13 mm (range 9-21 mm). The mean duration of hospitalization was 1.3 days. Bleeding and intentional perforation were all successfully managed during the procedure and did not result in any clinically significant adverse event. CONCLUSION: A device-assisted EFTR using a commercially available EMR kit is a safe and feasible method for the endoscopic resection of small gastric extrovert SETs.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32079120

RESUMO

The water-level fluctuation zone (WLFZ) is a transitional zone between terrestrial and aquatic ecosystems. Plant communities that are constructed artificially in the WLFZ can absorb and retain nutrients such as nitrogen (N) and phosphorus (P). However, the microbial community composition and function associated with this process have not been elucidated. In this study, four artificially constructed plant communities, including those of herbs (Cynodon dactylon and Chrysopogon zizanioides), trees (Metasequoia glyptostroboides), and shrubs (Salix matsudana) from the newly formed WLFZ of the Danjiangkou Reservoir were evaluated. The bacterial community compositions were analyzed by 16S rRNA gene sequencing using a MiSeq platform, and the functions of these communities were assessed via Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis. The results showed that the bacterial communities primarily comprised 362 genera from 24 phyla, such as Proteobacteria, Acidobacteria, Actinobacteria, and Gemmatimonadetes, showing the richness of the community composition. Planting altered the bacterial community composition, with varying effects observed among the different plant types. The bacterial community functional analysis revealed that these bacteria were primarily associated with six biological metabolic pathway categories (e.g., metabolism, genetic information processing, and environmental information processing) with 34 subfunctions, showing the richness of community functions. The planting of M. glyptostroboides, S. matsudana, and C. dactylon improved the metabolic capabilities of bacterial communities. N- and P-cycling gene analysis showed that planting altered the N- and P-cycling metabolic capacities of soil bacteria. The overall N- and P-metabolic capacity was highly similar between C. dactylon and C. zizanioides samples and between S. matsudana and M. glyptostroboides samples. The results of this study provide a preliminary analysis of soil bacterial community structure and function in the WLFZ of the Danjiangkou Reservoir and provides a reference for vegetation construction in this zone.

7.
Dig Dis Sci ; 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31894488

RESUMO

BACKGROUND: Predictors besides symptoms of obstruction indicating small bowel stenosis are little known. AIMS: To detect predictors of small bowel stenosis in balloon-assisted enteroscopy. METHODS: Over a 6-year period, 461 patients had enteroscopy for suspected small intestinal disease. Details of clinical manifestations, medical history, demographic characteristics, findings of examinations, information on enteroscopy, and treatment were retrospectively collected based on medical records. Small bowel stenosis was defined as stricture that over-tube cannot go through in enteroscopy. Univariate and multivariate analyses were performed to identify predictors for small bowel stenosis. RESULTS: A total of 314 patients had definite diagnosis after enteroscopy, imaging modalities, and/or even surgical exploration. They were included in this study for analyses. Mean age for them was 48.2 years old (range 15-81 years). Small bowel stenosis was present in 59 patients (18.8%). Analyses showed that CT/MRI indicating stenosis was significantly associated with severe stenosis (p = 0.014) but insignificant related to general stenosis (p = 0.097). Predictive factors that accompanied stenosis were age ≥ 60 years (OR = 2.1, 95% CI 1.1-4.0), underweight (BMI ≤ 18.5) (OR = 3.4, 95% CI 1.4-8.4), symptoms of obstruction (OR = 3.6, 95% CI 1.8-7.4), and overt small bowel bleeding (OR = 0.5, 95% CI 0.2-0.9). CONCLUSIONS: Small bowel stenosis more tended to occur to patients with symptoms of obstruction, no overt small bowel bleeding, age ≥ 60 years, or underweight.

8.
Ecotoxicol Environ Saf ; 190: 110130, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31918252

RESUMO

Environmental pollutants like methylmercury (MeHg) can bring devastating neurotoxicity to animals and human beings. Gut microbiota has been found to demethylate MeHg and promote the excretion of Hg through feces. However, the impacts of MeHg on gut microbiota and metabolites related to gut-brain interactions were less studied in mammals. The object of this study was to investigate the impacts of acute MeHg exposure on gut microbiome and metabolites together with its impact on gut integrity and related biological responses in rats. Rats were exposed to MeHg through oral administration and were sacrificed after 24 h 16 S rRNA gene sequencing was used to study the perturbance to gut microbiome and liquid chromatography mass spectrometry (LC-MS) was used for metabolomics profiling. It was found that gut was one of the target tissues of MeHg. MeHg induce the changes of intestinal microbial community structure and induce the regulating neuron activity change of intestinal neurotransmitters and metabolites on intestinal neurotransmitters and metabolites regulating the neuron activity. This was supported by the increased BDNF level. These findings may suggest a potential new mechanism regarding the neurotoxicity of MeHg. The protocols used in this study may also be applied to understand the neurotoxicity of other environmental neurotoxins like Pb, Mn, polychlorinated biphenyls, and pesticides, etc and to screen the neurotoxicity of emerging environmental contaminants.


Assuntos
Poluentes Ambientais/toxicidade , Microbioma Gastrointestinal/fisiologia , Compostos de Metilmercúrio/toxicidade , Testes de Toxicidade Aguda , Animais , Encéfalo , Cromatografia Líquida , Poluentes Ambientais/análise , Fezes/química , Microbioma Gastrointestinal/genética , Humanos , Hidrocarbonetos Aromáticos/análise , Intestinos/química , Masculino , Espectrometria de Massas/métodos , Mercúrio/análise , Metabolômica/métodos , Microbiota , Praguicidas/análise , Bifenilos Policlorados/análise , Ratos
9.
Biophys J ; 118(4): 898-908, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-31699333

RESUMO

Defective nitrate signaling in plants causes disorder in nitrogen metabolism, and it negatively affects nitrate transport systems, which toggle between high- and low-affinity modes in variable soil nitrate conditions. Recent discovery of a plasma membrane nitrate transceptor protein NRT1.1-a transporter cum sensor-provides a clue on this toggling mechanism. However, the general mechanistic description still remains poorly understood. Here, we illustrate adaptive responses and regulation of NRT1.1-mediated nitrate signaling in a wide range of extracellular nitrate concentrations. The results show that the homodimeric structure of NRT1.1 and its dimeric switch play an important role in eliciting specific cytosolic calcium waves sensed by the calcineurin-B-like calcium sensor CBL9, which activates the kinase CIPK23, in low nitrate concentration that is, however, impeded in high nitrate concentration. Nitrate binding at the high-affinity unit initiates NRT1.1 dimer decoupling and priming of the Thr101 site for phosphorylation by CIPK23. This phosphorylation stabilizes the NRT1.1 monomeric state, acting as a high-affinity nitrate transceptor. However, nitrate binding in both monomers, retaining the unmodified NRT1.1 state through dimerization, attenuates CIPK23 activity and thereby maintains the low-affinity mode of nitrate signaling and transport. This phosphorylation-led modulation of NRT1.1 activity shows bistable behavior controlled by an incoherent feedforward loop, which integrates nitrate-induced positive and negative regulatory effects on CIPK23. These results, therefore, advance our molecular understanding of adaptation in fluctuating nutrient availability and are a way forward for improving plant nitrogen use efficiency.

10.
Spectrochim Acta A Mol Biomol Spectrosc ; 227: 117678, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31676151

RESUMO

Two novel Schiff-base fluorescent probers SQ and NQ based on 8-hydroxyquinoline moiety were designed and synthesized. The both probes were capable of binding with Al3+ by naked eye detection to produce a significant fluorescence enhancement response with a detection limit of 1.48 × 10-8 and 4.23 × 10-8 M, respectively. At the same time, the formed complexes SQ-Al3+ and NQ-Al3+ could sequentially detect F-, and the detection limits of F- were determined to be 1.64 × 10-7 and 3.58 × 10-8 M, respectively. The "off-on-off" fluorescence response process demonstrated that the binding were reversible. The probes were further successfully utilized to detect Al3+ and F- in vitro PC12 cells.

11.
J Cell Mol Med ; 24(1): 655-670, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31691530

RESUMO

The antitumour effect of melittin (MEL) has recently attracted considerable attention. Nonetheless, information regarding the functional role of MEL in bladder cancer (BC) is currently limited. Herein, we investigated the effect of MEL on critical module genes identified in BC. In total, 2015 and 4679 differentially expressed genes (DEGs) associated with BC were identified from the GSE31189 set and The Cancer Genome Atlas database, respectively. GSE-identified DEGs were mapped and analysed using Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes analyses to determine BC-involved crucial genes and signal pathways. Coupled with protein-protein interaction network and Molecular Complex Detection analyses, Modules 2 and 4 were highlighted in the progression of BC. In in-vitro experiments, MEL inhibited the proliferation, migration, and invasion of UM-UC-3 and 5637 cells. The expression of NRAS, PAK2, EGFR and PAK1 in Module 4-enriched in the MAPK signalling pathway-was significantly reduced after treatment with MEL at concentrations of 4 or 6 µg/mL. Finally, quantitative reverse transcription-polymerase chain reaction and Western blotting analyses revealed MEL inhibited the expression of genes at the mRNA (ERK1/2, ERK5, JNK and MEK5), protein (ERK5, MEK5, JNK and ERK1/2) and phosphorylation (p-ERK1/2, p-JNK, and p-38) levels. This novel evidence indicates MEL exerts effects on the ERK5-MAK pathway-a branch of MAPK signalling pathway. Collectively, these findings provide a theoretical basis for MEL application in BC treatment.

12.
Arch Biochem Biophys ; 679: 108208, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31760124

RESUMO

AMP-activated protein kinase (AMPK) is a metabolic energy sensor that plays a critical role in cancer cell survival and growth. While the physical microenvironment is believed to influence tumor growth and progression, its role in AMPK regulation remains largely unknown. In the present study, we evaluated AMPK response to mechanical forces and its interaction with other mechano-responsive signaling proteins, FAK and Src. Using genetically encoded biosensors that can detect AMPK activities at different subcellular locations (cytosol, plasma membrane, nucleus, mitochondria, and Golgi apparatus), we observed that AMPK responds to shear stress in a subcellular location-dependent manner in breast cancer cells (MDA-MB-231). While normal epithelial cells (MCF-10A) also similarly responded to shear stress, they are less sensitive to shear stress compared to MDA-MB-231 cells. Inhibition of FAK and Src significantly decreased the basal activity level of AMPK at all five subcellular locations in MDA-MB-231 cells and selectively blocked shear stress-induced AMPK activation. Moreover, testing with cytoskeletal drugs revealed that myosin II might be the critical mediator of shear stress-induced AMPK activation in MDA-MB-231 cells. These findings suggest that breast cancer cells and normal epithelial cells may have different mechanosensitivity in AMPK signaling and that FAK and Src as well as the myosin II-dependent signaling pathway are involved in subcellular AMPK mechanotransduction in breast cancer cells.

13.
Spectrochim Acta A Mol Biomol Spectrosc ; 226: 117631, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31622824

RESUMO

A highly sensitive and selective indole-based probe IHT exhibited obvious color change from colorless to violet easily detected by naked eye as well as 'turn on' fluorescence response to Cu2+ ion at physiological pH condition. The detection limit was determined to be as low as 8.93 × 10-8 M, which was much lower than drinking water permission concentrations by the United States Environmental Protection Agency. The 1:2 binding mechanism was well confirmed by fluorescence titration, Job's plot, HRMS, IR analysis and DFT calculations. Furthermore, the probe IHT was successfully used for fluorescence imaging of Cu2+ ion in living cells.

14.
Spectrochim Acta A Mol Biomol Spectrosc ; 225: 117493, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31494382

RESUMO

A novel Schiff base fluorescent probe 7-Hydroxy-8-(((2-(hydroxymethyl)quinolin-8-yl)imino)methyl)-coumarin (XL) consist of formylcoumarin and aminoquinoline moieties was synthesized for dual detection of Zn2+ and Al3+ ions. Probe XL exhibited high selective and sensitive response towards Zn2+ and Al3+ ions through different color changes and significant fluorescence turn-on response (270 fold higher for Zn2+ and 230 fold higher for Al3+) in MeOH-H2O (4/1, v/v) over other cations, with detection limits (LOD) as low as 3.75 × 10-8 and 1.14 × 10-8 M, respectively. Moreover, probe XL exhibited preferential selectivity for Al3+ through displacing Zn2+ from the XL-Zn2+ complex by ligand-to-ligand transfer process. The binding mechanism of intramolecular charge transfer (ICT) were proposed from fluorescence and UV-vis titrations, Job's plot, 1H NMR titration, HRMS and DFT calculations. The probe was proven to be suitable for actual samples detection of Zn2+ and Al3+ ions. The complex XL-Zn2+ and XL-Al3+ exhibited dramatic fluorescent "turn-off" properties for PPi and PPi/F- respectively through snatching metal ions and released free XL. Moreover, probe XL showed low biotoxicity and sequentially "off-on-off" fluorescent bio-imaging of Zn2+/Al3+ and PPi/F- in PC12 cells.

15.
Spectrochim Acta A Mol Biomol Spectrosc ; 228: 117790, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31757708

RESUMO

Two novel coumarin based fluorescent sensors CHP and CHS have been synthesized for the sequential detection of Zn2+ ion and phosphate anion (PA) in DMF/HEPES buffer medium (1/5 v/v, 10 mM, pH = 7.4). On the addition of Zn2+ ion to the solution of CHP or CHS resulted in a pronounced fluorescence enhancement, accompanying noticeable color change (under UV or daylight), while there was hardly obvious change with other competing metal ions co-existing. The detection limits (DL) of CHP and CHS toward Zn2+ were separately determined as 1.03 × 10-7 (R2 = 0.9886) and 1.87 × 10-7 (R2 = 0.9902). The PET binding processes were affirmed by spectroscopic techniques, HRMS experiments and theoretical calculations. Subsequently, the CHP-Zn2+ or CHS-Zn2+ complexes showed high selectivity fluorescence quenching toward PA by snatching Zn2+ ion from its complex and the binding processes were reversible. DLs were calculated as 2.07 × 10-7 M (R2 = 0.9928) and 2.63 × 10-7 M (R2 = 0.9954), respectively. Furthermore, the cell imaging experiments demonstrated that the sensors were capable of detecting of Zn2+ and PA in vitro cells.

16.
Eur J Pediatr ; 179(4): 611-617, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31863304

RESUMO

For Peutz-Jeghers syndrome (PJS) patients, small bowel polyps develop and result in symptoms at an early age. Balloon-assisted enteroscopy (BAE) is verified as a safe and efficient choice to evaluate and remove small intestinal polyps in adult PJS. But the safety of BAE, especially BAE-facilitated polypectomy for young pediatrics, is little known. This prospective study focused on the effectiveness and safety of BAE-facilitated polypectomy in small bowel for young pediatric PJS. PJS patients (aged 0-14 years old) with BAE (including both single-balloon and double-balloon enteroscopies) were included from 1 September 2012 to 30 April 2018. The demographic data, medical history, and details of BAE were recorded. BAE-related complications and symptom relief after BAE were evaluated and compared between the PJS patients aged 5-10 years old (the younger pediatric group) and those aged 11-14 years old (the older pediatric group). A total of 41 pediatric PJS patients (5-14 years old) subjected to 82 BAEs were included. BAE-facilitated polypectomy was performed for 33 children (80.5%), and 242 polyps in small bowel were removed. For 10 (24.4%) patients, one or more giant polyps (maximum diameter larger than 5 cm) were removed. For eight patients, no polypectomy was done as no polyps were observed (six subjects) or not suitable for BAE-facilitated polypectomy (two subjects) because of high risk of perforation. The complication rates of BAE and BAE-facilitated polypectomy were 1.2% (1/82) and 1.8% (1/55), and the symptom relief rate was 70.8% (17/24). Compared with the older pediatric group, the younger pediatric group showed no increased BAE complication rate (0.0% vs. 5.0%, p = 0.488) and a comparable rate of symptom relief after BAE therapy (80.8% vs. 55.6%, p = 0.356).Conclusion: BAE-facilitated polypectomy in young pediatric PJS is safe and effective.What is known:• Small bowel evaluation and prophetic polypectomy are important for pediatric PJS patients to avoid polyp-related intussusception, obstruction, and bleeding.• BAE polypectomy was a recommended intervention for removing small bowel polyps in adult PJS patients.What is new:• BAE-facilitated small bowel polypectomy is safe and effective for young pediatric PJS, even for those aged less than 10 years old.

17.
Brain Behav Immun ; 83: 87-111, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31560941

RESUMO

Systemic inflammation enhances the risk and progression of Alzheimer's disease (AD). Lipopolysaccharide (LPS), a potent pro-inflammatory endotoxin produced by the gut, is found in excess levels in AD where it associates with neurological hallmarks of pathology. Sex differences in susceptibility to inflammation and AD progression have been reported, but how this impacts on LPS responses remains under investigated. We previously reported in an APP/PS1 model of AD that systemic LPS administration rapidly altered hippocampal metabolism in males. Here, we used untargeted metabolomics to comprehensively identify hippocampal metabolic processes occurring at onset of systemic inflammation with LPS (100 µg/kg, i.v.) in APP/PS1 mice, at an early pathological stage, and investigated the sexual dimorphism in this response. Four hours after LPS administration, pathways regulating energy metabolism, immune and oxidative stress responses were simultaneously recruited in the hippocampi of 4.5-month-old mice with a more protective response in females despite their pro-inflammatory and pro-oxidant metabolic signature in the absence of immune stimulation. LPS induced comparable behavioural sickness responses in male and female wild-type and APP/PS1 mice and comparable activation of both the serotonin and nicotinamide pathways of tryptophan metabolism in their hippocampi. Elevations in N-methyl-2-pyridone-5-carboxamide, a major toxic metabolite of nicotinamide, correlated with behavioural sickness regardless of sex, as well as with the LPS-induced hypothermia seen in males. Males also exhibited a pro-inflammatory-like downregulation of pyruvate metabolism, exacerbated in APP/PS1 males, and methionine metabolism whereas females showed a greater cytokine response and anti-inflammatory-like downregulation of hippocampal methylglyoxal and methionine metabolism. Metabolic changes were not associated with morphological markers of immune cell activation suggesting that they constitute an early event in the development of LPS-induced neuroinflammation and AD exacerbation. These data suggest that the female hippocampus is more tolerant to acute systemic inflammation.

18.
Ecotoxicol Environ Saf ; 188: 109897, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31704327

RESUMO

Mercury (Hg) pollution seriously threatens food safety and has attracted global attention. Phytoextraction, due to its low cost, applicability, and environmental friendliness, is considered a new technology for clean-up of heavy metal contamination in the environment. However, the low bioavailability of Hg in polluted areas greatly limits the applicability of phytoextraction. Here, we compared the effects of six common chelating ligands on the absorption and transport of Hg in maize (Zea mays L.), which has a high biomass and short growth cycle. The results showed that the root length and biomass of maize seedlings of the groups treated with the six chelating ligands (EDTA, iodide, ammonium, thiosulfate, thiocyanate, and thiocarbamide) did not change compared with those of the non-treated groups. Co-exposure to Hg and each chelating ligand markedly alleviated the inhibitory effect induced by Hg. Iodide treatment resulted in the lowest root Hg content and highest translocation factor (TF) value, while ammonium treatment gave rise to the highest shoot Hg concentration and lowest TF. Compared with other chelating ligands, thiosulfate exhibited the maximum alleviation of Hg toxicity and achieved the highest concentration of Hg in the roots and aerial parts. Moreover, the TF and Hg accumulation in the thiosulfate and Hg co-exposed group were much higher than those in the group exposed to Hg alone. This finding suggests that, among these common chelating ligands, thiosulfate compounds have great potential for Hg phytoextraction, while the others can immobilize Hg in polluted areas.


Assuntos
Quelantes/farmacologia , Mercúrio/análise , Poluentes do Solo/análise , Tiossulfatos/farmacologia , Zea mays/química , Bioacumulação , Biodegradação Ambiental , Disponibilidade Biológica , Transporte Biológico , Biomassa , Ligantes , Raízes de Plantas/efeitos dos fármacos , Plântula/efeitos dos fármacos , Zea mays/efeitos dos fármacos , Zea mays/crescimento & desenvolvimento
19.
Brain Res Bull ; 154: 9-20, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31626954

RESUMO

Hypertension is a common complication of metabolic abnormalities associated with cardiovascular system and characterized by sexual dimorphism in mammals. Fibroblast growth factor-21 (FGF-21) plays a critical role in metabolic-disorder related hypertension through the afferent loop of baroreflex. However, the gender difference in FGF-21-mediated blood pressure (BP) regulation via sexual dimorphic expression of FGFRs in the nodose (NG) and nucleus tractus solitarius (NTS) were not elucidated in physiological and genomic form of hypertension. The gene and protein expression of FGFRs were tested by qRT-PCR, immunoblotting and immunostaining; the serum level of FGF21 was tested using ELISA; The BP was monitored while FGF21 was nodose microinjected. The results showed that more potent BP reduction was confirmed in female vs. male rats by nodose microinjection of rhFGF-21 along with higher expression of FGFR2 and FGFR4 in the nodose compared with age-match male and ovariectomized (OVX) rats, rather than other receptor subtypes, which is consistent well with immunohistochemical analysis. Additionally, serum FGF-21 was significantly higher in female-WKY, and this level of FGF-21 was dramatically declined in spontaneous hypertensive rats (SHR) with significant down-regulation of FGFR1/R4 for male-SHR and FGFR2/FGFR4 for female-SHR, respectively. Apparently, high BP of SHR of either sex could be reduced by rhFGF-21 nodose microinjection. These data extends our current understanding that sexual-specific distribution/expression of FGF-21/FGFRs is likely to contribute at least partially to sexual dimorphism of baroreflex afferent function on BP regulation in rats. FGF-21-mdiated BP reduction sheds new light on clinical management of primary/genomic form of hypertension.

20.
Life Sci ; 242: 117228, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31881227

RESUMO

AIMS: Berberine (BBR) is reported to induce apoptosis and inhibit migration of leukemic cells, but the underlying pharmacological mechanisms have not been fully revealed. This study aims to investigate the possible mechanisms from the perspective of autophagy. MAIN METHODS: P-53-null leukemic cell lines Jurkat and U937 were used for the in vitro study. MDC staining was used for observation of autophagy in leukemic cells, and Western blot analysis was for determination of the expression levels of autophagy-associated proteins. Apoptosis of the leukemic cells was detected by flow cytometry. Cellular location of MDM2 was observed with immunofluorescence staining. Ubiquitination of MDM2 was assessed by immunoprecipitation. Male 6-8-week-old NOD/SCID mice were used for evaluating the effect of BBR on chemotherapy sensitivity in vivo. KEY FINDINGS: BBR induced autophagy in p53-null leukemic cells, which was inhibited by autophagy inhibitors 3-methyladenine. 3-methyladenine also inhibited BBR-induced apoptosis in leukemic cells. In addition, BBR not only decreased MDM2 mRNA expression, but also enhanced MDM2 self-ubiquitination in leukemic cells. Forced overexpression of MDM2 reversed the effect of BBR on autophagy and apoptosis. Furthermore, BBR promoted doxorubicin-induced autophagy and cell death in the leukemic cells and overexpression of MDM2 suppressed these effects. In vivo, BBR combined with doxorubicin achieved better therapeutic effect than doxorubicin alone. SIGNIFICANCE: MDM2 inhibits autophagy and apoptosis in leukemic cells in a p53-independent manner. BBR induces autophagy in p53-null leukemic cells through downregulating MDM2 expression at both transcriptional and post-transcriptional levels, which may contribute to the anti-cancer effect of BBR in leukemia.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Berberina/farmacologia , Células Jurkat/efeitos dos fármacos , Leucemia Experimental/tratamento farmacológico , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Células U937/efeitos dos fármacos , Animais , Western Blotting , Citometria de Fluxo , Imunofluorescência , Humanos , Células Jurkat/metabolismo , Leucemia Experimental/metabolismo , Masculino , Camundongos Endogâmicos NOD , Camundongos SCID , Transplante de Neoplasias , Reação em Cadeia da Polimerase em Tempo Real , Células U937/metabolismo , Ubiquitinação
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