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1.
World J Pediatr ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32193830

RESUMO

BACKGROUND: Increased meningitis caused by extensively drug-resistant bacillary presents a significant challenge in antibiotic selection. The aim of our study was to evaluate the efficacy and safety of polymyxin in the treatment of post-neurosurgical meningitis due to the extensively drug-resistant bacillary in children. METHODS: We performed a retrospective study on post-neurosurgical meningitis caused by the extensively drug-resistant bacillary in children, who were treated with polymyxin for ≥ 3 days. RESULTS: Among five post-neurosurgical meningitis cases that were included, the children were infected by Acinetobacter baumannii (n = 3), Klebsiella pneumonia (n = 1), and Pseudomonas aeruginosa (n = 1). The drug susceptibility test showed that they were extensively drug-resistant bacillary. Two patients received intravenous polymyxin E. Three children received intravenous combined with intraventricular injection of polymyxin B. One patient infected by Klebsiella pneumonia eventually died of septic shock. No serious adverse effects of polymyxin were observed. CONCLUSIONS: Polymyxin is a safe and effective therapy for post-neurosurgical, multidrug-resistant bacillary meningitis in children.

2.
NPJ Biofilms Microbiomes ; 6(1): 8, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060424

RESUMO

The microbiota colonizing the root endophytic compartment and surrounding rhizosphere soils contribute to plant growth and health. However, the key members of plant soil and endophytic microbial communities involved in inhibiting or assisting pathogen invasion remain elusive. By utilizing 16S high-throughput sequencing and a molecular ecological network (MEN) approach, we systematically studied the interactions within bacterial communities in plant endophytic compartments (stem and root) and the surrounding soil (bulk and rhizosphere) during bacterial wilt invasion. The endophytic communities were found to be strongly influenced by pathogen invasion according to analysis of microbial diversity and community structure and composition. Endophytic communities of the infected plants were primarily derived from soil communities, as assessed by the SourceTracker program, but with rare migration from soil communities to endophytic communities observed in healthy plants. Soil and endophytic microbiomes from infected plants showed modular topology and greater complexity in network analysis, and a higher number of interactions than those in healthy plants. Furthermore, interactions among microbial members revealed that pathogenic Ralstonia members were positively correlated with several bacterial genera, including Delftia, Stenotrophomonas, Bacillus, Clostridium XlVa, Fontibacillus, Acidovorax, Herminiimonas, and three unclassified bacterial genera, in infected plant roots. Our findings indicated that the pathogen invasion in the rhizosphere and endophytic compartments may be highly associated with bacteria that are normally not detrimental, and sometimes even beneficial, to plants.

3.
Aging (Albany NY) ; 12(4): 3662-3681, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32074079

RESUMO

Magnetic field (MF) is being used in antitumor treatment; however, the underlying biological mechanisms remain unclear. In this study, the potency and mechanism of a previously published tumor suppressing MF exposure protocol were further investigated. This protocol, characterized as a 50 Hz electromagnetic field modulated by static MF with time-average intensity of 5.1 mT, when applied for 2 h daily for over 3 consecutive days, selectively inhibited the growth of a broad spectrum of tumor cell lines including lung cancer, gastric cancer, pancreatic cancer and nephroblastoma. The level of intracellular reactive oxygen species (ROS) increased shortly after field exposure and persisted. Subsequently, pronounced DNA damage and activation of DNA repair pathways were identified both in vitro and in vivo. Furthermore, use of free radical scavenger alleviated DNA damage and partially reduced cell death. Finally, this field was found to inhibit cell proliferation, and simultaneously induced two types of programmed cell death, apoptosis and ferroptosis. In conclusion, this tumor suppressing MF could determine cell fate through ROS-induced DNA damage, inducing oxidative stress and activation of the DNA damage repair pathways, eventually lead to apoptosis and ferroptosis, as well as inhibition of tumor growth.

4.
Biosci Rep ; 40(2)2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-31985007

RESUMO

OBJECTIVES: Sperm-associated antigen 5 (SPAG5), a spindle-binding protein, regulates the process of mitosis. The present study focused on the relationship between SPAG5 expression and the clinicopathological characteristics and prognosis of ovarian cancer. METHODS: First, we used the Gene Expression Omnibus (GEO) database to analyze SPAG5 expression in ovarian cancer and its clinical relevance. Subsequently, qPCR test was used to detect SPAG5 mRNA expression in 20 cases of ovarian cancer. The expression of SPAG5 protein in a tissue microarray containing 102 cases of ovarian cancer was detected by immunohistochemistry. Cox regression and Kaplan-Meier survival analyses were performed to identify the prognostic factors for the 102 ovarian cancer patients. RESULTS: In the GEO datasets, SPAG5 mRNA expression was significantly higher in ovarian cancer tissues than that in normal ovarian tissues (P < 0.001). qPCR and immunohistochemistry showed that SPAG5 expression in ovarian cancer tissues was significantly higher than that in paracancerous tissues (P = 0.002, P < 0.001). The high expression of SPAG5 in ovarian cancer was correlated with histological type (P = 0.009), lymph node metastasis (P = 0.001), distant metastasis (P = 0.001), TNM stage (P = 0.001), and prognosis (P = 0.001). The Kaplan-Meier curve indicated that rates of disease-free survival (DFS) and overall survival (OS) were even lower in patients with high SPAG5 expression. Multivariate analysis showed that SPAG5 expression (P = 0.001) and TNM staging (P = 0.002) were independent prognostic factors for the DFS of ovarian cancer. CONCLUSIONS: These results suggest that high SPAG5 expression was correlated with multiple clinicopathological features of ovarian cancer and can be used as an evaluation indicator for a poor ovarian cancer prognosis.

5.
Sci Rep ; 9(1): 17731, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31776360

RESUMO

Mitochondria-generated reactive oxygen species (mROS) are frequently associated with DNA damage and cell cycle arrest, but physiological increases in mROS serve to regulate specific cell functions. T3 is a major regulator of mROS, including hydrogen peroxide (H2O2). Here we show that exogenous thyroid hormone (T3) administration increases cardiomyocyte numbers in neonatal murine hearts. The mechanism involves signaling by mitochondria-generated H2O2 (mH2O2) acting via the redox sensor, peroxiredoxin-1, a thiol peroxidase with high reactivity towards H2O2 that activates c-Jun N-terminal kinase-2α2 (JNK2α2). JNK2α2, a relatively rare member of the JNK family of mitogen-activated protein kinases (MAPK), phosphorylates c-Jun, a component of the activator protein 1 (AP-1) early response transcription factor, resulting in enhanced insulin-like growth factor 1 (IGF-1) expression and activation of proliferative ERK1/2 signaling. This non-canonical mechanism of MAPK activation couples T3 actions on mitochondria to cell cycle activation. Although T3 is regarded as a maturation factor for cardiomyocytes, these studies identify a novel redox pathway that is permissive for T3-mediated cardiomyocyte proliferation-this because of the expression of a pro-proliferative JNK isoform that results in growth factor elaboration and ERK1/2 cell cycle activation.

6.
Mol Cell ; 76(3): 516-527.e7, 2019 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-31492635

RESUMO

The PTEN tumor suppressor is frequently mutated or deleted in cancer and regulates glucose metabolism through the PI3K-AKT pathway. However, whether PTEN directly regulates glycolysis in tumor cells is unclear. We demonstrate here that PTEN directly interacts with phosphoglycerate kinase 1 (PGK1). PGK1 functions not only as a glycolytic enzyme but also as a protein kinase intermolecularly autophosphorylating itself at Y324 for activation. The protein phosphatase activity of PTEN dephosphorylates and inhibits autophosphorylated PGK1, thereby inhibiting glycolysis, ATP production, and brain tumor cell proliferation. In addition, knockin expression of a PGK1 Y324F mutant inhibits brain tumor formation. Analyses of human glioblastoma specimens reveals that PGK1 Y324 phosphorylation levels inversely correlate with PTEN expression status and are positively associated with poor prognosis in glioblastoma patients. This work highlights the instrumental role of PGK1 autophosphorylation in its activation and PTEN protein phosphatase activity in governing glycolysis and tumorigenesis.


Assuntos
Neoplasias Encefálicas/enzimologia , Glioblastoma/enzimologia , Glucose/metabolismo , Glicólise , PTEN Fosfo-Hidrolase/metabolismo , Fosfoglicerato Quinase/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Glioblastoma/genética , Glioblastoma/patologia , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , PTEN Fosfo-Hidrolase/genética , Fosfoglicerato Quinase/genética , Fosforilação , Prognóstico , Transdução de Sinais , Fatores de Tempo , Carga Tumoral , Tirosina
7.
PLoS One ; 14(9): e0221827, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31532782

RESUMO

Chloroplasts significantly influence species phylogenies because of their maternal inheritance and the moderate evolutionary rate of their genomes. Avocado, which is a member of the family Lauraceae, has received considerable attention from botanists, likely because of its position as a basal angiosperm. However, there is relatively little avocado genomic information currently available. In this study, six complete avocado chloroplast genomes from three ecological races were assembled to examine the sequence diversity among the three avocado ecological races. A comparative genomic analysis revealed that 515 simple sequence repeat loci and 176 repeats belonging to four other types were polymorphic across the six chloroplast genomes. Three highly variable regions (trnC-GCA-petN, petN-psbM, and petA-psbJ) were identified as highly informative markers. A phylogenetic analysis based on 79 common protein-coding genes indicated that the six examined avocado accessions from three ecological races form a monophyletic clade. The other three genera belonging to the Persea group clustered to form a sister clade with a high bootstrap value. These chloroplast genomes provide important genetic information for future attempts at identifying avocado races and for the related biological research.

8.
Int J Mol Sci ; 20(17)2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31450745

RESUMO

Avocado (Persea americana Mill.) is an economically important crop because of its high nutritional value. However, the absence of a sequenced avocado reference genome has hindered investigations of secondary metabolism. For next-generation high-throughput transcriptome sequencing, we obtained 365,615,152 and 348,623,402 clean reads as well as 109.13 and 104.10 Gb of sequencing data for avocado mesocarp and seed, respectively, during five developmental stages. High-quality reads were assembled into 100,837 unigenes with an average length of 847.40 bp (N50 = 1725 bp). Additionally, 16,903 differentially expressed genes (DEGs) were detected, 17 of which were related to carotenoid biosynthesis. The expression levels of most of these 17 DEGs were higher in the mesocarp than in the seed during five developmental stages. In this study, the avocado mesocarp and seed transcriptome were also sequenced using single-molecule long-read sequencing to acquired 25.79 and 17.67 Gb clean data, respectively. We identified 233,014 and 238,219 consensus isoforms in avocado mesocarp and seed, respectively. Furthermore, 104 and 59 isoforms were found to correspond to the putative 11 carotenoid biosynthetic-related genes in the avocado mesocarp and seed, respectively. The isoform numbers of 10 out of the putative 11 genes involved in the carotenoid biosynthetic pathway were higher in the mesocarp than those in the seed. Besides, alpha- and beta-carotene contents in the avocado mesocarp and seed during five developmental stages were also measured, and they were higher in the mesocarp than in the seed, which validated the results of transcriptome profiling. Gene expression changes and the associated variations in gene dosage could influence carotenoid biosynthesis. These results will help to further elucidate carotenoid biosynthesis in avocado.


Assuntos
Carotenoides/metabolismo , Regulação da Expressão Gênica de Plantas , Persea/genética , Persea/metabolismo , Sementes/genética , Sementes/metabolismo , Transcriptoma , Vias Biossintéticas , Biologia Computacional/métodos , Dosagem de Genes , Perfilação da Expressão Gênica , Ontologia Genética , Metaboloma , Metabolômica/métodos , Anotação de Sequência Molecular , Desenvolvimento Vegetal/genética
9.
Mar Drugs ; 17(7)2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31288374

RESUMO

Marine organisms are recognized as a source of compounds with interesting biological activities. Vibrio neocaledonicus has been reported on for its high effectiveness against corrosion in metals but it has been little studied for its chemical and biological activities. In this study, four compounds were isolated from V. neocaledonicus: indole (1); 1H-indole-3-carboxaldehyde (2); 4-hydroxybenzaldehyde (3) and Cyclo (-Pro-Tyr) (4); using a bioassay-guided method, since in a previous study it was found that the ethyl acetate extract was active on the enzymes acetylcholinesterase (AChE), alpha-glucosidase (AG) and xanthine oxidase (XO). The inhibitory activities of the three compounds against AChE, AG and XO was also evaluated. In addition, the enzymatic inhibitory activity of indole to the toxins from the venom of Bothrops asper was tested. Results showed that indole exhibited strong inhibitory activity to AG (IC50 = 18.65 ± 1.1 µM), to AChE, and XO (51.3% and 44.3% at 50 µg/mL, respectively). 1H-indole-3-carboxaldehyde displayed strong activity to XO (IC50 = 13.36 ± 0.39 µM). 4-hydroxybenzaldehyde showed moderate activity to XO (50.75% at 50 µg/mL) and weak activity to AChE (25.7% at 50 µg/mL). Furthermore, indole showed a significant in vitro inhibition to the coagulant effect induced by 1.0 µg of venom. The findings were supported by molecular docking. This is the first comprehensive report on the chemistry of V. neocaledonicus and the bioactivity of its metabolites.


Assuntos
Organismos Aquáticos/química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Enzimas/química , Vibrio/química , Benzaldeídos/química , Benzaldeídos/farmacologia , Indóis/química , Indóis/farmacologia , Simulação de Acoplamento Molecular/métodos
10.
Forensic Sci Int ; 301: 394-401, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31234110

RESUMO

Blotter papers laced with lysergic acid diethylamide (LSD) have been abused traditionally for their hallucinogenic properties. In recent years, new psychedelic phenethylamines such as 2,5-dimethoxyphenethylamines (2C) and their N-benzylhydroxy (25-NBOH) and N-2-methoxybenzyl derivatives (25-NBOMe) have emerged in the illicit drugs market. Traditionally, gas chromatography-mass spectrometry (GC-MS) is regarded as the gold standard for illicit drugs analysis. However, with the emergence of new psychoactive substances (NPS) which are thermally labile (such as the 25-NBOH drugs which undergo thermal degradation to their respective 2C drugs), alternative non-thermal techniques have to be developed in order to prevent misidentification. In this study, a single, targeted, non-thermal analytical method using the liquid chromatography-tandem mass spectrometry (LC-MS/MS) to simultaneously identify these new phenethylamines and their derivatives was developed and validated. Twelve phenethylamines and their derivatives, as well as LSD were simultaneously analysed using the LC-MS/MS in a multiple reaction monitoring (MRM) detection mode. The method developed was validated and applied for the analysis of phenethylamines and their derivatives commonly found in seized exhibits such as blotter papers and Ecstasy tablets.

11.
PeerJ ; 7: e7092, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31218132

RESUMO

Background: Studies have shown that the occurrence and development of IgA nephropathy (IgAN) are genetically susceptible, but the relationship between vitamin D receptor (VDR) gene polymorphisms and renal function in IgAN patients is unclear. Methods: We investigated the relationship between VDR FokI (rs2228570) single nucleotide polymorphism (SNP) and renal function and related clinicopathologic parameters in IgAN patients. Clinical and pathological data of 282 IgAN patients treated at the First Affiliated Hospital of Guangxi Medical University were collected, and FokI genotypes were determined by PCR and direct sequencing. Patients were divided into the renal dysfunction group and normal renal function (control) group by estimated glomerular filtration rate (eGFR) and serum creatinine level. Results: Frequencies of TT genotype and T allele in the renal dysfunction group were higher than those of the control group. Blood urea nitrogen, serum phosphorus (P), proportions of mesangial cell proliferation, interstitial fibrosis/tubular atrophy and crescents in T allele carriers were higher than those in non-T allele carriers, while eGFR and 25-Hydroxyvitamin D3 were lower in T allele carriers than non-T allele carriers. Multiple linear regression analysis showed that eGFR was affected by FokI genotypes in IgAN patients. Logistics regression analysis showed that middle and elderly age, elevated P, intact parathyroid hormone and TT genotype were independent risk factors for renal dysfunction in IgAN patients; the odds ratio of carrying the TT genotype was as high as 84.77 (P < 0.05 for all). Conclusions: IgA nephropathy patients carrying the VDR FokI TT genotype have an increased risk of renal dysfunction. VDR FokI SNP is closely related to renal function, calcium-phosphate metabolism, and related pathological damage in IgAN patients.

12.
Mol Cancer Ther ; 18(9): 1587-1592, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31209181

RESUMO

We and others have reported that the anticancer activity of L-asparaginase (ASNase) against asparagine synthetase (ASNS)-positive cell types requires ASNase glutaminase activity, whereas anticancer activity against ASNS-negative cell types does not. Here, we attempted to disentangle the relationship between asparagine metabolism, glutamine metabolism, and downstream pathways that modulate cell viability by testing the hypothesis that ASNase anticancer activity is based on asparagine depletion rather than glutamine depletion per se. We tested ASNase wild-type (ASNaseWT) and its glutaminase-deficient Q59L mutant (ASNaseQ59L) and found that ASNase glutaminase activity contributed to durable anticancer activity against xenografts of the ASNS-negative Sup-B15 leukemia cell line in NOD/SCID gamma mice, whereas asparaginase activity alone yielded a mere growth delay. Our findings suggest that ASNase glutaminase activity is necessary for durable, single-agent anticancer activity in vivo, even against ASNS-negative cancer types.

13.
J Biomed Nanotechnol ; 15(7): 1432-1442, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31196348

RESUMO

Smart wet-spun fibers for highly programmable release of therapeutic drug have been rarely reported. Herein, thermalresponsive composite fibers were successfully prepared by core-sheath wet-spinning technology in present study. They consisted of a model drug of natural antibacterial berberine chloride hydrate (BCH) and a drug carrier of temperature responsive shape memory polyurethane (SMPU). The obtained composite fibers featured with well-controlled microscopic morphologies, exhibiting significantly enhanced thermal stability and superb mechanical properties. In vitro drug release test and corresponding release kinetics study were performed for investigation of BCH's release behavior. Results demonstrated that the release behaviors of BCH from the core-sheath fibers were pH-dependent, influenced by both diffusion from pore channels and the solubility of BCH in the release mediums, and BCH imbedded only in core part showed a longer release period compared with that in both core and sheath parts of the composite fibers. More importantly, the release rate of BCH can be simply controlled by changing the initial shapes of fibers through stretching and fixation of the stretched deformations. Furthermore, the antibacterial durability of the smart composites fibers was demonstrated and tracked according to the growth inhibition against both negative E. coli and positive S. aureus bacteria strains. All these results suggest that the developed composite fibers can be promising candidates as smart drug delivery vehicles for highly adjustable doses of target drugs towards practical applications.


Assuntos
Berberina/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Escherichia coli , Umidade , Staphylococcus aureus
14.
Biosci Rep ; 39(6)2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31152111

RESUMO

OBJECTIVES: The present study investigated the correlation between α B-crystallin (CRYAB, HSPB5) and p53 expression in ovarian cancer and further analyzed the relationship between their expression and clinicopathology and the prognostic value of their co-expression in ovarian cancer. METHODS: CRYAB and p53 expression was assessed using immunohistochemistry on ovarian cancer tumor tissues from 103 cases and validated in an independent group of 103 ovarian cancer patients. RESULTS: High CRYAB and p53 expression rates in ovarian cancer tissues were 61.17% (63/103) and 57.28% (59/103), respectively, and their expression was positively correlated (r = 0.525, P=0.000). High CRYAB expression was significantly correlated with tumor size (P=0.028), lymph node metastasis (P=0.000), distant metastasis (P=0.005), tumor node metastasis (TNM) stage (P=0.002), and survival (P=0.000), while high p53 expression was significantly correlated with tumor size (P=0.006), pathological grade (P=0.023), lymph node metastasis (P=0.001), and survival (P=0.000). Further studies found that the high CRYAB and p53 co-expression was also significantly correlated with pathological grade (P=0.024), lymph node metastasis (P=0.000), Distant metastasis (P=0.015), TNM stage (P=0.013), and survival (P=0.000). High expression of either CRYAB or p53 and high co-expression of CRYAB and p53 were significantly correlated with poor disease-free survival (DFS) and overall survival (OS), respectively (P<0.05). Patients with high CRYAB and p53 co-expression had the worst prognoses among the groups. In addition, multivariate Cox regression models showed that high expression of either CRYAB or p53 and high co-expression of CRYAB and p53 were independent prognostic factors for DFS and OS (P<0.05). Moreover, the positive correlation and prognostic value of CRYAB and p53 expression were verified in another independent dataset. CONCLUSIONS: We demonstrated that patients with high CRYAB and p53 co-expression in ovarian cancer have significantly increased risks of recurrence, metastasis, and death compared with other patients. Therefore, more frequent follow-up of patients with high CRYAB and p53 co-expression is required. Our results also suggest that combination therapy with CRYAB inhibitors and p53 blockers may benefit future treatment of ovarian cancer patients with high co-expression of CRYAB and p53.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31173666

RESUMO

BACKGROUND: Low muscularity (LM) is associated with high mortality in the Caucasian critically ill population. Muscularity can be accurately measured by the skeletal muscle index (SMI; cm2 /m2 ) generated by computed tomography (CT). This study aimed to establish the overall and sex-specific cutoff values that predict hospital mortality in an Asian critically ill population. METHODS: This single-center, retrospective, observational study included patients aged ≥18 years with an abdominal CT conducted within 72 hours of admission to the intensive care unit. SMI generated from CT images at the level of the mid-third lumbar vertebra were extracted from the medical records. Area under the receiver operating characteristic curves (AUC) was generated to determine the SMI cutoff values for hospital mortality. Association between LM (defined by SMI cutoff value) and hospital mortality was further evaluated by multivariable logistic regression. RESULTS: In a sample of 228 patients, the overall SMI cutoff value (cm2 /m2 ) for hospital mortality was 42.0 (AUC: 0.637; sensitivity: 66.7%, specificity: 56.8%), whereas it was 46.5 in males and 35.3 in females. More males than females had LM (51.4% vs 37.5%), and >40% of overweight/obese patients had LM. Patients with LM were older and had a longer duration of mechanical ventilation and hospitalization. After adjusting for known confounders, LM independently predicted hospital mortality in the overall sample (adjusted odds ratio: 2.42; 95% CI 1.16-5.03; P = 0.003) and in both sexes. CONCLUSION: This study established a set of SMI cutoff values that predict hospital mortality. LM is independently associated with hospital mortality.

16.
Theranostics ; 9(7): 1864-1877, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037144

RESUMO

Uremic cardiomyopathy and muscle atrophy are associated with insulin resistance and contribute to chronic kidney disease (CKD)-induced morbidity and mortality. We hypothesized that restoration of miR-26a levels would enhance exosome-mediated microRNA transfer to improve muscle wasting and cardiomyopathy that occur in CKD. Methods: Using next generation sequencing and qPCR, we found that CKD mice had a decreased level of miR-26a in heart and skeletal muscle. We engineered an exosome vector that contained Lamp2b, an exosomal membrane protein gene fused with a muscle-specific surface peptide that targets muscle delivery. We transfected this vector into muscle satellite cells and then transduced these cells with adenovirus that expresses miR-26a to produce exosomes encapsulated miR-26a (Exo/miR-26a). Exo/miR-26a was injected once per week for 8 weeks into the tibialis anterior (TA) muscle of 5/6 nephrectomized CKD mice. Results: Treatment with Exo/miR-26a resulted in increased expression of miR-26a in skeletal muscle and heart. Overexpression of miR-26a increased the skeletal muscle cross-sectional area, decreased the upregulation of FBXO32/atrogin-1 and TRIM63/MuRF1 and depressed cardiac fibrosis lesions. In the hearts of CKD mice, FoxO1 was activated, and connective tissue growth factor, fibronectin and collagen type I alpha 1 were increased. These responses were blunted by injection of Exo/miR-26a. Echocardiograms showed that cardiac function was improved in CKD mice treated with Exo/miR-26a. Conclusion: Overexpression of miR-26a in muscle prevented CKD-induced muscle wasting and attenuated cardiomyopathy via exosome-mediated miR-26a transfer. These results suggest possible therapeutic strategies for using exosome delivery of miR-26a to treat complications of CKD.

17.
Clin Transl Gastroenterol ; 10(5): 1-12, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31033506

RESUMO

OBJECTIVES: Chronic hepatitis B (CHB) can progress into liver fibrosis and cirrhosis with poor outcomes. Early and accurate diagnosis of liver fibrosis/cirrhosis is important to guide the preventive strategy of their related complications. METHODS: A Chinese multicenter cross-sectional study was conducted to develop and validate a novel noninvasive program for staging liver fibrosis in untreated patients with CHB. Liver histology was evaluated independently by 2 pathologists. The alanine aminotransferase ratio, Hepascore, and aspartate aminotransferase to platelet index values were calculated. Liver stiffness measurement (LSM) and diameter of the spleen were measured. Logistic regression with ℓ1 penalty of regression coefficients was used to select the optimal predictors. The diagnostic accuracy for the stage of liver fibrosis was assessed by the area under the receiver operator characteristic curve with 95% confidence interval (CI). RESULTS: A total of 1,200 patients with CHB were included, of whom 800 and 400 were in training and validation sets, respectively. LSM, platelets, age, hyaluronic acid, and diameter of the spleen were the top 5 predictors associated with any stage of liver fibrosis and integrated into a novel noninvasive program, named as the Chin-CHB score. The area under the receiver operator characteristic curve of the Chin-CHB score was 0.893 (95% CI: 0.77-0.92) for diagnosing significant fibrosis, 0.897 (95% CI: 0.85-0.95) for advanced fibrosis, and 0.909 (95% CI: 0.87-0.95) for cirrhosis. The diagnostic performance of the Chin-CHB score was similar between training and validation sets. The Chin-CHB score had better diagnostic performance than aspartate aminotransferase to platelet index, alanine aminotransferase ratio, LSM alone, and Hepascore for diagnosing any stage of liver fibrosis. CONCLUSIONS: The Chin-CHB score had good diagnostic performance for any stage of liver fibrosis.

19.
Infant Behav Dev ; 55: 88-99, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30947141

RESUMO

Relatively little work has examined potential interactions between child intrinsic factors and extrinsic environmental factors in the development of negative affect in early life. This work is important because high levels of early negative affectivity have been associated with difficulties in later childhood adjustment. We examined associations between infant frontal electroencephalogram (EEG), maternal parenting behaviors, and children's negative affect across the first two years of life. Infant baseline frontal EEG asymmetry was measured at 5 months; maternal sensitivity and intrusiveness were observed during mother-child interaction at 5 and 24 months; and mothers provided reports of toddler negative affect at 24 months. Results indicated that maternal sensitive behaviors at 5 months were associated with less negative affect at 24 months, but only for infants with left frontal EEG asymmetry. Similarly, maternal sensitive behaviors at 24 months were associated with less toddler negative affect at 24 months, but only for infants with left frontal EEG asymmetry. In contrast, maternal intrusive behaviors at 5- and 24-months were associated with greater toddler negative affect, but only for infants with right frontal EEG asymmetry at 5-months. Findings suggest that levels of negative affect in toddlers may be at least partially a result of interactions between children's own early neurophysiological functioning and maternal behavior during everyday interactions with children in the first two years of life.


Assuntos
Afeto/fisiologia , Desenvolvimento Infantil/fisiologia , Eletroencefalografia/métodos , Lobo Frontal/fisiologia , Comportamento do Lactente/fisiologia , Comportamento Materno/fisiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Comportamento do Lactente/psicologia , Estudos Longitudinais , Masculino , Comportamento Materno/psicologia , Relações Mãe-Filho/psicologia , Mães/psicologia
20.
Food Chem ; 288: 146-153, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30902274

RESUMO

Avocado (Persea americana) is a tropical fruit that has drawn great interest its oil for foods and cosmetic industries; however, avocado oil processing by-product is a potential source of edible protein. Herein, edible protein was prepared from defatted avocado meal, and it's physicochemical, functional and emulsion properties were investigated. The avocado protein showed U-shaped exhibiting strong effect of pH, and a minimum solubility being observed at pH 4.5, confirming the isoelectric point of avocado protein. Nutritionally, the avocado protein contains all the essential amino acids. Avocado protein provided higher water and oil absorption capacities, higher radical scavenging capacity but lower in-vitro digestibility compared with soy protein. Furthermore, the avocado protein as emulsifier afforded a stability oil-in-water emulsion system, resulting in a greater emulsifying stability than that of soy protein. The present results highlight the potential source of edible protein from avocado oil processing by-products for functional food ingredients.


Assuntos
Emulsões , Persea/química , Óleos Vegetais/química , Proteínas de Plantas/química , Digestão , Interações Hidrofóbicas e Hidrofílicas , Proteínas de Plantas/metabolismo , Solubilidade , Propriedades de Superfície
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