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1.
J Nanosci Nanotechnol ; 20(2): 1224-1231, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383122

RESUMO

The layered potassium niobate, K4Nb6O17, is known as a photocatalyst for hydrogen production from water splitting under UV light. Here we show that potassium niobate nanosheets can be obtained by exfoliation of K4Nb6O17 followed by proton exchange. Photocatalytic water splitting has been improved in this work by loading Rh nanoparticles as cocatalyst. The catalysts were characterized by powder X-ray diffraction (XRD), X-ray photoelectron spectroscopy analysis (XPS), and ultraviolet-visible spectroscopy (UV-vis), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Their photocatalytic activities were in (i) an aqueous MeOH, used as sacrificial hole scavengers for hydrogen production and (ii) pure water for hydrogen and oxygen production under UV light irradiation. The potassium niobate nanosheets with uniform dispersion of Rh nanoparticles exhibited a very high photocatalytic overall water splitting activity, where the H2 production and O2 production rate were 142 µmol h-1 g-1 and 68 µmol h-1 g-1, which was about 10 times higher than that exhibited by the origin K4Nb6O17 photocatalyst.

2.
Food Chem ; 306: 125300, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31562927

RESUMO

Chlorophyll is a valuable bioactive compound, which is used as a natural food coloring agent and a photosensitizer for photodynamic therapy because of its antioxidant properties, antimutagenic ability, and near-infrared fluorescence. However, chlorophyll is unstable when it comes to retaining its antioxidant activity, when exposed to oxygen, high temperature, or light environments. To enhance the stability of chlorophyll, a polymer encapsulation method was proposed. Polycaprolactone (PCL) was employed to encapsulate the chlorophyll, and the particles size of the composites was controlled through droplet microfluidics. The composites (chlorophyll-encapsulated PCL particles) were characterized through UV-VIS spectrometry, SEM, optical microscopy, and light exposure. The particles were spherical, with diameters adjustable from 68 to 247 µm. Additionally, the chlorophyll-encapsulated PCL particles exhibited considerably prolonged chlorophyll stability. The solid microparticle is more convenient for storage and transportation, and have great potential for application in the food industry.

3.
Front Immunol ; 10: 2405, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681295

RESUMO

The pathogenic effect of mutant HTT (mHTT) which causes Huntington disease (HD) are not restricted to nervous system. Such phenotypes include aberrant immune responses observed in the HD models. However, it is still unclear how this immune dysregulation influences the innate immune response against pathogenic infection. In the present study, we used transgenic Drosophila melanogaster expressing mutant HTT protein (mHTT) with hemocyte-specific drivers and examined the immune responses and hemocyte function. We found that mHTT expression in the hemocytes did not affect fly viability, but the numbers of circulating hemocytes were significantly decreased. Consequently, we observed that the expression of mHTT in the hemocytes compromised the immune responses including clot formation and encapsulation which lead to the increased susceptibility to entomopathogenic nematode and parasitoid wasp infections. In addition, mHTT expression in Drosophila macrophage-like S2 cells in vitro reduced ATP levels, phagocytic activity and the induction of antimicrobial peptides. Further effects observed in mHTT-expressing cells included the altered production of cytokines and activation of JAK/STAT signaling. The present study shows that the expression of mHTT in Drosophila hemocytes causes deficient cellular and humoral immune responses against invading pathogens. Our findings provide the insight into the pathogenic effects of mHTT in the immune cells.

4.
Biomed Res Int ; 2019: 4370382, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31687390

RESUMO

Background: Studies of previous cohorts have demonstrated a controversial association between extreme body mass index (BMI) and complication rates following total hip arthroplasty (THA). The purpose of this study was to compare 30-day perioperative complications in underweight (BMI <18.50 kg/m2), normal-weight (BMI 18.50-24.99 kg/m2), overweight (BMI 25.00-29.99 kg/m2), class I obesity (BMI 30.00-34.99 kg/m2), and morbidly obese (BMI ≥35.00 kg/m2) groups. Methods: We performed a cohort study including patients who underwent unilateral primary THA by a single surgeon between January 2010 and December 2015 at our institution. We assessed 30-day complications, operation time, operative blood loss, and length of hospital stay. Results: We identified 1565 primary THAs that were performed in patients with varying BMI levels. Compared with the normal-weight patients, the morbidly obese group had a higher 30-day complication rate (8.9% vs. 2.4%), longer operative time (79 minutes vs. 70 minutes), and more blood loss (376 mL vs. 302 mL). Underweight patients did not present any 30-day complications, and there were no differences among underweight and normal-weight patients regarding complication rates, operative time, or blood loss. The mean length of hospital stay was comparable among the different BMI groups. In the multivariate regression model, higher BMI was not associated with a higher risk of 30-day complications. Independent risk factors for 30-day complications were advanced age, prolonged operative time, and cardiovascular comorbidities. Conclusion: Although increased operative time, blood loss, and perioperative complications were seen in the morbidly obese patients, BMI alone was not an independent risk factor for a higher 30-day complication rate. Therefore, our data suggest clinicians should make elderly patients aware of increased 30-day complications before the procedure, particularly those with cardiovascular comorbidities. Withholding THA solely on the basis of BMI is not justified.

5.
Theranostics ; 9(24): 7251-7267, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695766

RESUMO

In this study, we performed a comprehensively analysis of gene expression and DNA methylation data to establish diagnostic, prognostic, and recurrence models for hepatocellular carcinoma (HCC). Methods: We collected gene expression and DNA methylation datasets for over 1,200 clinical samples. Integrated analyses of RNA-sequencing and DNA methylation data were performed to identify DNA methylation-driven genes. These genes were utilized in univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses to build a prognostic model. Recurrence and diagnostic models for HCC were also constructed using the same genes. Results: A total of 123 DNA methylation-driven genes were identified. Two of these genes (SPP1 and LCAT) were chosen to construct the prognostic model. The high-risk group showed a markedly unfavorable prognosis compared to the low-risk group in both training (HR = 2.81; P < 0.001) and validation (HR = 3.06; P < 0.001) datasets. Multivariate Cox regression analysis indicated the prognostic model to be an independent predictor of prognosis (P < 0.05). Also, the recurrence model successfully distinguished the HCC recurrence rate between the high-risk and low-risk groups in both training (HR = 2.22; P < 0.001) and validation (HR = 2; P < 0.01) datasets. The two diagnostic models provided high accuracy for distinguishing HCC from normal samples and dysplastic nodules in the training and validation datasets, respectively. Conclusions: We identified and validated prognostic, recurrence, and diagnostic models that were constructed using two DNA methylation-driven genes in HCC. The results obtained by integrating multidimensional genomic data offer novel research directions for HCC biomarkers and new possibilities for individualized treatment of patients with HCC.

6.
World Neurosurg ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31698129

RESUMO

OBJECTIVE: Conventional laminectomy for spine decompression involves inherent complications resulting from perioperative traumatization of posterior structures. Minimally invasive decompression was developed to address these issues. Full endoscopic spine surgery has shifted the paradigm from disc pathology to spinal stenosis by overcoming the limitation of bony procedures with evolving endoscopic instruments. However, steep learning curve restricts the development of endoscopic decompression. The purpose of this study is to describe full endoscopic uniportal unilateral laminotomy for bilateral decompression (ULBD) through the interlaminar approach and to evaluate its efficacy and safety in 2 years of follow-up. METHODS: 106 patients (45 males, 61 females) with degeneration lumbar stenosis involving 165 segments were enrolled from April 2015 to June 2017, and treated by full endoscopic uniportal ULBD. We made an 8-mm incision and used a general-size endoscope (working channel 4.3 mm) to avoid neurological compromise during the demonstration. RESULTS: The visual analogue scale (VAS) results for back pain revealed a significant reduction from preoperative 6.8±2.1 to 1.7±1.7 after 2 years (p<0.001). The VAS results for leg pain revealed a significant reduction from preoperative 7.6±1.3 to 1.3±1.6 after 2 years (p<0.001). The Oswestry Disability Index showed significant improvement from preoperative 62.0±13.9 to 14.6±15.7 after 2 years (p<0.001). The average operation time was 68.9±10.0 minutes per level. One case had iatrogenic durotomy, one case underwent revision surgery due to incomplete decompression, and two cases had delayed wound healing. CONCLUSIONS: This procedure obtained successful and satisfactory outcomes for patients, and was more feasible for surgeons.

7.
Blood Adv ; 3(21): 3214-3227, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31698452

RESUMO

A major driver of multiple myeloma (MM) is thought to be aberrant signaling, yet no kinase inhibitors have proven successful in the clinic. Here, we employed an integrated, systems approach combining phosphoproteomic and transcriptome analysis to dissect cellular signaling in MM to inform precision medicine strategies. Unbiased phosphoproteomics initially revealed differential activation of kinases across MM cell lines and that sensitivity to mammalian target of rapamycin (mTOR) inhibition may be particularly dependent on mTOR kinase baseline activity. We further noted differential activity of immediate downstream effectors of Ras as a function of cell line genotype. We extended these observations to patient transcriptome data in the Multiple Myeloma Research Foundation CoMMpass study. A machine-learning-based classifier identified surprisingly divergent transcriptional outputs between NRAS- and KRAS-mutated tumors. Genetic dependency and gene expression analysis revealed mutated Ras as a selective vulnerability, but not other MAPK pathway genes. Transcriptional analysis further suggested that aberrant MAPK pathway activation is only present in a fraction of RAS-mutated vs wild-type RAS patients. These high-MAPK patients, enriched for NRAS Q61 mutations, have inferior outcomes, whereas RAS mutations overall carry no survival impact. We further developed an interactive software tool to relate pharmacologic and genetic kinase dependencies in myeloma. Collectively, these predictive models identify vulnerable signaling signatures and highlight surprising differences in functional signaling patterns between NRAS and KRAS mutants invisible to the genomic landscape. These results will lead to improved stratification of MM patients in precision medicine trials while also revealing unexplored modes of Ras biology in MM.

8.
Sci Rep ; 9(1): 16836, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727954

RESUMO

Bowel microbiota is a "metaorgan" of metabolisms on which quantitative readouts must be performed before interventions can be introduced and evaluated. The study of the effects of probiotic Clostridium butyricum MIYAIRI 588 (CBM588) on intestine transplantees indicated an increased percentage of the "other glycan degradation" pathway in 16S-rRNA-inferred metagenomes. To verify the prediction, a scoring system of carbohydrate metabolisms derived from shotgun metagenomes was developed using hidden Markov models. A significant correlation (R = 0.9, p < 0.015) between both modalities was demonstrated. An independent validation revealed a strong complementarity (R = -0.97, p < 0.002) between the scores and the abundance of "glycogen degradation" in bacteria communities. On applying the system to bacteria genomes, CBM588 had only 1 match and ranked higher than the other 8 bacteria evaluated. The gram-stain properties were significantly correlated to the scores (p < 5 × 10-4). The distributions of the scored protein domains indicated that CBM588 had a considerably higher (p < 10-5) proportion of carbohydrate-binding modules than other bacteria, which suggested the superior ability of CBM588 to access carbohydrates as a metabolic driver to the bowel microbiome. These results demonstrated the use of integrated counts of protein domains as a feasible readout for metabolic potential within bacteria genomes and human metagenomes.

9.
Sci Rep ; 9(1): 17042, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31728066

RESUMO

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

10.
J Nutr Biochem ; 75: 108260, 2019 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-31707285

RESUMO

A maternal high-fat (HF) diet sensitizes offspring to the adverse effects of postnatal HF intake and can lead to metabolic dysregulation. Resveratrol, a natural polyphenolic compound found in grapes and red wine, could help to relieve metabolic syndrome dysregulation. Since the gut microbiota is known to be closely related to metabolic homeostasis, this study aimed to investigate the impact of a combination of maternal and postweaning HF diets on the gut microbiota and whether resveratrol could relieve the gut dysbiosis associated with metabolic dysregulation. Sprague-Dawley dams were sustained on either a chow or HF diet before mating, during pregnancy and during lactation. Their offspring were randomly fed chow or a HF diet after weaning. Four experimental groups were generated: CC (maternal/postnatal chow diet), HC (maternal HF/postnatal chow diet), CH (maternal chow/postnatal high-fat diet) and HH (maternal/postnatal HF diet). A fifth group consisted of HH with resveratrol treatment. We found that both maternal and postnatal HF exposure has a distinct effect on the gut microbiota metagenome of offspring. Maternal HF diet exposure decreased plasma acetate, propionate and butyrate level, while postnatal HF diet exposure decreased plasma acetate level in adult life. The metabolic dysregulation programed by the maternal and postnatal HF diets was related to the relevant gut microbiota. Resveratrol treatment ameliorated the altered plasma propionate level related to maternal HF and postnatal HF diet treatment. Resveratrol treatment also improved most of the altered metabolic dysregulation and related dysbiosis programmed by maternal and postnatal HF diet exposure.

13.
Neuroscience ; 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31689489

RESUMO

Acceleration of cytoskeletal remodeling in regenerated axons is crucial for a fully functional recovery following peripheral nerve injury (PNI). Melatonin plays important roles in cell differentiation and protection of cytoskeleton stability, thus, the present study aimed to investigate whether melatonin can enhance neurite outgrowth and promote cytoskeletal remodeling in a PNI animal model and in differentiated neurons. End-to-side neurorrhaphy (ESN) rat model was used for assessing cytoskeletal rearrangement in regenerated axon. Subject rats received 1 mg/kg/day melatonin injection for one month. The amplitude of compound muscle action potentials and the number of re-innervated motor end plates on target muscles were assessed to represent the functional recovery after ESN. Melatonin treatment enhanced functional recovery after ESN, compared to the saline treated group. Additionally, in spinal cord and peripheral nerve tissue, animals receiving melatonin displayed enhanced expression of GAP43 and ß3-tubulin one month after ESN, and an increased number of re-innervated motor end plates on their target muscle. In vitro analysis revealed that melatonin treatment significantly promoted neurite outgrowth, and increased expression of melatonin receptors as well as ß3-tubulin in mouse neuroblastoma Neuro-2a (N2a) cells. Treatment with a melatonin receptor antagonist, luzindole, significantly suppressed melatonin receptors and ß3-tubulin expression. Importantly, we found that melatonin treatment suppressed activation of calmodulin-dependent protein kinase II (CaMKII) in vitro and in vivo, suggesting that the ß3-tubulin remodeling may occur via CaMKII-mediated Ca2+ signaling. These results suggested that melatonin may promote functional recovery after PNI by accelerating cytoskeletal remodeling through the melatonin receptor-dependent pathway.

14.
Nanotoxicology ; : 1-19, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703536

RESUMO

Mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) are central microdomains of the ER that interact with mitochondria. MAMs provide an essential platform for crosstalk between the ER and mitochondria and play a critical role in the local transfer of calcium (Ca2+) to maintain cellular functions. Despite the potential uses of superparamagnetic iron oxide nanoparticles (SPIO-NPs) in biomedical applications, the hepatotoxicity of these nanoparticles (NPs) is not well characterized and little is known about the involvement of MAMs in ER-mitochondria crosstalk. We studied SPIO-NPs-associated hepatotoxicity in vitro and in vivo. In vitro, human normal hepatic L02 cells were exposed to SPIO-NPs (2.5, 7.5, and 12.5 µg/mL) for 6 h and SPIO-NPs (12.5 µg/mL) was found to induce apoptosis. In vivo, SPIO-NPs induced liver injury when mice were intravenously injected with 20 mg/kg body weight SPIO-NPs for 24 h. Based on both in vitro and in vivo studies, we found that the structure and Ca2+ transport function of MAMs were perturbated and an accumulation of cyclooxygenase-2 (COX-2) in MAMs fractions was increased upon treatment of SPIO-NPs. The interaction between COX-2 and the components of MAMs, in terms of IP3R-GRP75-VDAC1 complex, was also revealed. Furthermore, the role of COX-2 in SPIO-NPs-associated hepatotoxicity was investigated by modifying the expression of COX-2. We demonstrated that COX-2 increases the structural and functional ER-mitochondria coupling and enhances the efficacy of ER-mitochondria Ca2+ transfer through the MAMs, thus sensitizing hepatocytes to a mitochondrial Ca2+ overload-dependent apoptosis. Taken together, our findings link SPIO-NPs-triggered hepatotoxicity with ER-mitochondria Ca2+ crosstalk which is mediated by COX-2 and provide mechanistic insight into the impact of interorganelle ER-mitochondria communication on hepatic nanotoxicity.

15.
Nutrients ; 11(11)2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31689986

RESUMO

OBJECTIVE: To investigate the hepatoprotective mechanisms of taxifolin in mice with acute liver injury induced by CCl4. METHODS: ICR (Institute of Cancer research) mice were orally pretreated using taxifolin for 7 consecutive days and were then given single intraperitoneal (i.p.) injections of 0.2% CCl4 (10 mL/kg body weight, i.p.). Liver injury was then determined using assays of serum alanine aminotransferase (sALT) and serum aspartate aminotransferase (sAST). Further, to investigate the hepatoprotective mechanisms of taxifolin, we determined malondialdehyde (MDA) levels and superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GRd) activities. RESULTS: CCl4-induced liver injury led to significant increases in sALT and sAST activities, and these increases were limited by taxifolin and silymarin (Sily) pretreatments. Histological analyses also indicated that taxifolin and Sily decreased the range of liver lesions in CCl4-treated mice and vacuole formation, neutrophil infiltration, and necrosis were visibly reduced. In addition, SOD, GPx, and GRd activities were increased and MDA levels were decreased after taxifolin and Sily treatments. CONCLUSION: The hepatoprotective mechanisms of taxifolin and Sily are related to decreases in MDA levels presumably due to increased antioxidant enzyme activities. These outcomes suggest that taxifolin mitigates acute liver injury resulted from CCl4 in mice, demonstrating the hepatoprotective effects of taxifolin.

16.
J Am Chem Soc ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31692351

RESUMO

The activity and accessibility of MoS2 edge sites are critical to deliver high hydrogen evolution reaction (HER) efficiency. Here, a porous carbon network confining ultrasmall N-doped MoS2 nanocrystals (N-MoS2/CN) is fabricated by a self-templating strategy, which realizes synergistically structural and electronic modulations of MoS2 edges. Experiments and density functional theory calculations demonstrate that the N dopants could activate MoS2 edges for HER, while the porous carbon network could deliver high accessibility of the active sites from N-MoS2 nanocrystals. Consequently, N-MoS2/CN possesses superior HER activity with an overpotential of 114 mV at 10 mA cm-2 and excellent stability over 10 h, delivering one of best MoS2-based HER electrocatalysts. Moreover, this study opens a new venue for optimizing materials with enhanced accessible catalytic sites for energy-related applications.

17.
Reprod Biol Endocrinol ; 17(1): 87, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666062

RESUMO

BACKGROUND: Morulas with delayed growth sometimes coexist with blastocysts. There is still limited evidence regarding the optimal disposal of surplus morulas. With the advancement of vitrification, the freezing-thawing technique has been widely applied to zygotes with 2 pronuclei, as well as embryos at the cleavage and blastocyst stages. The freezing of morulas, however, has rarely been discussed. The purpose of this study was to investigate whether these poor-quality and slow-growing morulas are worthy of cryopreservation. METHODS: This is a retrospective, observational, proof-of-concept study. A total of 1033 day 5/6 surplus morulas were cryopreserved from January 2015 to December 2018. The study included 167 women undergoing 180 frozen embryo transfer cycles. After the morulas underwent freezing-thawing procedures, their development was monitored for an additional day. The primary outcome was the blastocyst formation rate. Secondary outcomes were clinical pregnancy rate, live birth rate and abortion rate. RESULTS: A total of 347 surplus morulas were thawed. All studied morulas showed delayed compaction (day 5, n = 329; day 6, n = 18) and were graded as having low (M1, n = 54), medium (M2, n = 138) or high (M3, n = 155) fragmentation. The post-thaw survival rate was 79.3%. After 1 day in extended culture, the blastocyst formation rate was 66.6%, and the top-quality blastocyst formation rate was 23.6%. The day 5 morulas graded as M1, M2, and M3 had blastocyst formation rates of 88.9, 74.0, and 52.8% (p < 0.001), respectively, and the top-quality blastocyst formation rates were 64.8, 25.2, and 9.0% (p < 0.001), respectively. The clinical pregnancy rate was 33.6%. CONCLUSIONS: The post-thaw blastocyst formation rate was satisfactory, with approximately one-half of heavily fragmented morulas (M3) developing into blastocysts. Most of the poor-quality morulas were worth to freeze, with the reasonable goal of obtaining pregnancy and live birth. This alternative strategy may be a feasible approach for coping with poor-quality surplus morulas in non-PGS (preimplantation genetic screening) cycles.

18.
Sensors (Basel) ; 19(21)2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31683704

RESUMO

High dynamic range (HDR) has wide applications involving intelligent vision sensing which includes enhanced electronic imaging, smart surveillance, self-driving cars, intelligent medical diagnosis, etc. Exposure fusion is an essential HDR technique which fuses different exposures of the same scene into an HDR-like image. However, determining the appropriate fusion weights is difficult because each differently exposed image only contains a subset of the scene's details. When blending, the problem of local color inconsistency is more challenging; thus, it often requires manual tuning to avoid image artifacts. To address this problem, we present an adaptive coarse-to-fine searching approach to find the optimal fusion weights. In the coarse-tuning stage, fuzzy logic is used to efficiently decide the initial weights. In the fine-tuning stage, the multivariate normal conditional random field model is used to adjust the fuzzy-based initial weights which allows us to consider both intra- and inter-image information in the data. Moreover, a multiscale enhanced fusion scheme is proposed to blend input images when maintaining the details in each scale-level. The proposed fuzzy-based MNCRF (Multivariate Normal Conditional Random Fields) fusion method provided a smoother blending result and a more natural look. Meanwhile, the details in the highlighted and dark regions were preserved simultaneously. The experimental results demonstrated that our work outperformed the state-of-the-art methods not only in several objective quality measures but also in a user study analysis.

19.
J Psychiatr Res ; 120: 131-136, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31670261

RESUMO

Illicit drug use contributes to substantial morbidity and mortality. Drug scheduling, a legal measure in drug enforcement, is often structured as a hierarchy based on addiction tendency, abuse trends, and harm, but may lack data-driven evidence when classifying substances. Our study aims to measure addiction tendency and use trends based on real-world data. We used the open access database of National Police Agency, Ministry of the Interior in Taiwan and analyzed all daily criminal cases of illicit drugs from 2013 to 2017 and monthly illicit drug enforcement data from the same database from 2002 to 2017. We hypothesized that repeat and frequent use despite legal consequence may be a reflection of addictive behavior, and empirical mode decomposition was applied in analysis to calculate addiction tendency indices and intrinsic 15-year use trends. Our analysis showed heroin has the highest addiction index, followed by methamphetamine. 3,4-Methyl enedioxy methamphetamine, marijuana, and ketamine had lower addictive propensities. This result is consistent with most drug scheduling hierarchies. 15-year use trends of substances were consistent with previous epidemiological studies.

20.
Chemosphere ; 242: 125143, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31675585

RESUMO

Ochratoxin A (OTA), a mycotoxin widely found in foodstuffs, reportedly damages multiple brain regions in developing rodents, but the corresponding mechanisms have not been elucidated. In this study, zebrafish embryos at 6 h post fertilization (hpf) were exposed to various concentrations of OTA and the phenomenon associated with intracerebral hemorrhage was observed at 72 hpf. Exposure of embryos to OTA significantly increased their hemorrhagic rate in a dose-dependent manner. Large numbers of extravagated erythrocytes were observed in the midbrain/hindbrain areas of Tg(fli-1a:EGFP; gata1:DsRed) embryos following exposure to OTA. OTA also disrupted the vascular patterning, especially the arch-shaped central arteries (CtAs), in treated embryos. Histological analysis revealed a cavity-like pattern in their hindbrain ventricles, implying the possibility of cerebral edema. OTA-induced intracerebral hemorrhage and CtA vessel defects were partially reversed by the presence of miR-731 antagomir or the overexpression of prolactin receptor a (prlra); prlra is a downstream target of miR-731. These results suggest that exposure to OTA has a negative effect on cerebral vasculature development by interfering with the miR-731/PRLR axis in zebrafish.

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