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1.
Cardiol J ; 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32104900

RESUMO

BACKGROUND: The meta-analysis was performed to evaluate the effect of dissection and re-entry (DR) vs. wire escalation (WE) techniques on long-term clinical outcomes in patients with chronic total occlusion (CTO) lesions undergoing percutaneous coronary intervention (PCI). METHODS: Studies were searched in electronic databases from inception to September, 2019. Results were pooled using random effects model and fixed effects model and are presented as risk ratios (RR) with 95% confidence intervals (CI). RESULTS: Pooled analyses revealed that patients with DR techniques had overall higher complexity CTO lesions than patients with WE techniques and required a greater number of stents and a greater mean stent length. The "extensive" DR techniques may have a higher incidence of target vessel revascularization (TVR) (RR = 2.30, 95% CI: 1.77-2.98), in-stent restenosis (RR = 1.71, 95% CI: 1.30-2.23), in-stent reocclusion (RR = 1.86, 95% CI: 1.03-3.3) and death/MI/TVR (RR = 2.10, 95% CI: 1.71-2.58), when compared with WE techniques, during the long-term follow-up. However, "limited" DR techniques result in more promising outcomes, and are comparable to conventional WE techniques. CONCLUSIONS: Dissection and re-entry techniques were associated with increased risk of long-term negative clinical events, especially "extensive" DR techniques. However, "limited" DR techniques resulted in good long-term outcomes, comparable to WE techniques.

2.
J Cell Mol Med ; 24(5): 2772-2790, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32030886

RESUMO

Several microRNAs are associated with carcinogenesis and tumour progression. Herein, our observations suggest both miR24-2 and Pim1 are up-regulated in human liver cancers, and miR24-2 accelerates growth of liver cancer cells in vitro and in vivo. Mechanistically, miR24-2 increases the expression of N6-adenosine-methyltransferase METTL3 and thereafter promotes the expression of miR6079 via RNA methylation modification. Furthermore, miR6079 targets JMJD2A and then increased the tri-methylation of histone H3 on the ninth lysine (H3K9me3). Therefore, miR24-2 inhibits JMJD2A by increasing miR6079 and then increases H3K9me3. Strikingly, miR24-2 increases the expression of Pim1 dependent on H3K9me3 and METTL3. Notably, our findings suggest that miR24-2 alters several related genes (pHistone H3, SUZ12, SUV39H1, Nanog, MEKK4, pTyr) and accelerates progression of liver cancer cells through Pim1 activation. In particular, Pim1 is required for the oncogenic action of miR24-2 in liver cancer. This study elucidates a novel mechanism for miR24-2 in liver cancer and suggests that miR24-2 may be used as novel therapeutic targets of liver cancer.

3.
J Mater Chem B ; 8(11): 2307-2320, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32100786

RESUMO

In this study, a new type of ß-1,3-d-glucan porous microcapsule (GPM)-enveloped and folate conjugated chitosan-functional liposome (FCL), FCL@GPM, was developed for the potential oral co-delivery of chemotherapeutic drugs and quantum dots (QDs) with facilitated drug absorption and antitumor efficacy. In this dual-particulate system, multiple FCLs serve as the cores for effective loading, folate-mediated tumor-targeting, facilitated intracellular accumulation, and pH-responsive controlled release of chemotherapeutic agents, while a GPM acts as the shell for affording macrophage-mediated tumor selectivity. Gefitinib (GEF) was selected as a chemotherapeutic agent, while acid degradable ZnO QDs were selected due to their dual role as an anticancer agent for synergistic chemotherapy and as a fluorescent probe for potential cancer cellular imaging. The GEF and ZnO QD co-loaded FCL@GPMs (GEF/ZnO-FCL@GPMs) exhibited a prolonged release manner with limited release before uptake by intestinal cells. Furthermore, Peyer's patch uptake, macrophage uptake, cytotoxicity, and biodistribution of FCL@GPMs were tested. In addition, GEF and ZnO QD co-loaded FCLs (GEF/ZnO-FCLs) not only have a tumor acidity responsive release property, but also induce a superior cytotoxicity on cancer cells as compared to GEF. Moreover, a 1.75-fold increase in the bioavailability of GEF delivered from GEF/ZnO-FCL@GPMs as compared to its trademarked drug (Iressa®). As a result, GEF/ZnO-FCL@GPMs exerted a superior antitumor efficacy (1.47-fold) as compared to the trademarked drug in mice. Considered together, the developed FCL@GPMs, combining the unique physicochemical and biological benefits of FCLs and GPMs, possess great potential as an efficient delivery system for the co-delivery of chemotherapeutic agents and quantum dots.

4.
Dalton Trans ; 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32095791

RESUMO

Increasing interest in chromic materials is due to the growing demand. However, most chromic materials exhibit color changes in response to only one stimulus, but there are multiple stimuli in nature. Therefore, the construction of multistimuli responsive chromic materials still faces great challenges. Herein, a new multi-stimuli responsive coordination polymer [Zn2(2,3-PDC)2CV·(H2O)2]·H2O (1) (2,3-PDC = 2,3-pyridine dicarboxylic acid, CV = N,N'-4,4'-bipyridiniodipropionate) has been successfully synthesized, which exhibits photochromism under 300 W xenon lamp irradiation accompanied by an obvious color change from colorless to light blue. Meanwhile, compound 1 displays excellent thermochromic properties with a color change from colorless to light yellow when heated at 106 °C. The product of thermochromism is named 1T and the loss of free water improves the photoresponsive properties of 1T. Moreover, the compound can show differentiable detection of amines because of the electron-deficient nature of the viologen. Finally, 1 shows excellent electrochromic properties and turns from colorless to purple at E = -3 V. In conclusion, compound 1 exhibits multi-chromic behaviors in response to light, heat, amines and electricity, which are prominent in viologen based coordination polymers.

5.
Stem Cell Res Ther ; 11(1): 8, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900225

RESUMO

BACKGROUND: The functions of HULC have been demonstrated in several cancers. However, its mechanism has not been elucidated in human liver cancer stem cells. METHODS: Liver cancer stem cells were isolated from Huh7 cells; gene infection and tumorigenesis test in vitro and in vivo were performed. RESULTS: We demonstrate that HULC promotes growth of liver cancer stem cells in vitro and in vivo. Mechanistically, HULC enhances the expression of Sirt1 dependent on miR675 and then induces the cellular autophagy through Sirt1. HULC enhances CyclinD1 and thereby increases pRB and inhibited P21 WAF1/CIP 1 via autophagy-miR675-PKM2 pathway in human liver cancer stem cells. Ultimately, our results demonstrate that CyclinD1 is required for the oncogenic functions of HULC in liver cancer stem cells. CONCLUSIONS: It reveals the key molecular signaling pathways for HULC and provides important basic information for finding effective tumor therapeutic targets based on HULC.

6.
Cell ; 180(3): 502-520.e19, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-31983537

RESUMO

The tumor microenvironment (TME) is critical for tumor progression. However, the establishment and function of the TME remain obscure because of its complex cellular composition. Using a mouse genetic system called mosaic analysis with double markers (MADMs), we delineated TME evolution at single-cell resolution in sonic hedgehog (SHH)-activated medulloblastomas that originate from unipotent granule neuron progenitors in the brain. First, we found that astrocytes within the TME (TuAstrocytes) were trans-differentiated from tumor granule neuron precursors (GNPs), which normally never differentiate into astrocytes. Second, we identified that TME-derived IGF1 promotes tumor progression. Third, we uncovered that insulin-like growth factor 1 (IGF1) is produced by tumor-associated microglia in response to interleukin-4 (IL-4) stimulation. Finally, we found that IL-4 is secreted by TuAstrocytes. Collectively, our studies reveal an evolutionary process that produces a multi-lateral network within the TME of medulloblastoma: a fraction of tumor cells trans-differentiate into TuAstrocytes, which, in turn, produce IL-4 that stimulates microglia to produce IGF1 to promote tumor progression.

7.
Endocr Res ; : 1-12, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31986906

RESUMO

Purpose: To observe the expression of Nrg4, uncoupling protein-1 (UCP1), tumor necrosis factor α (TNFα), CD31, VE-cadherin/CDH5 and vascular endothelial growth factor A (VEGF-A) mRNA in abdominal subcutaneous (SC), omental (OM) adipose tissue in children with relation to anthropometric parameters. Further to verify the effect of inflammatory mediators on Nrg4 and UCP1 mRNA expression in adipocytes.Methods: Paired SC and OM adipose tissues were obtained from 58 children. In vitro, the adipocytes isolated from primary inguinal adipose tissue of mice were treated with TNFα (50 ng/ml) for 12-48 h. mRNA levels of Nrg4, UCP1 and TNFα were determined by real-time PCR.Results: Nrg4, UCP1, VEGF-A and CDH5 mRNA levels in SC were significantly higher than those in OM adipose tissue and the mRNA level of TNFα showed the opposite result. Moreover, Nrg4 and UCP1 mRNA in SC were significantly lower in overweight children compared to normal weight children. Nrg4 in SC and OM was negatively associated with BMISDS, WHtR. CDH55 mRNA in OM was negatively associated with WHR. VEGF-A was positively correlated with Nrg4 in SC. In vitro, Nrg4 and UCP1 mRNA levels in adipocytes were dose- and time-dependently decreased under TNFα treatment.Conclusions: Nrg4, UCP1, VEGF-A and CDH5 mRNA expression in adipose tissues display a depot-specific pattern. Nrg4 mRNA levels in adipose tissue are decreased with obesity and associated with WAT browning and angiogenesis. TNFα may be involved in the regulation of Nrg4 level in adipose tissue, which may be one of the causes of the down-regulation of Nrg4 expression in obesity with chronic inflammatory response.

8.
J Ethnopharmacol ; 250: 111965, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-31185267

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a complex gynecological endocrine disease commonly occurred in women of childbearing age. The main hallmark of PCOS includes elevated androgen production and insulin resistance (IR). Liuwei Dihuang Pills (LWDH Pills), a commonly prescribed traditional Chinese medicine (TCM) is widely used as a tonic prescription to treat diabetes, female menopause syndrome and other symptoms with'Kidney-Yin' deficiency. It has been reported the effects LWDH pills on PI3K/Akt signaling pathway in T2DM treatment. Recent studies have also indicated that the treatment of menopausal syndrome may be associated with the ovarian sexual hormone levels regulated by LWDH pills to alleviate female infertility. However, its potential benefits on PCOS have not been fully elucidated. AIM OF THE STUDY: The primary aim of this study was to investigate the alterations of PI3K/Akt pathway in polycystic ovary syndrome-insulin resistance (PCOS-IR) progression induced by letrozole combined with high fat diet (HFD) and then to explore the detailed mechanism of LWDH Pills to alleviate PCOS. MATERIALS AND METHODS: The female Sprague-Dawley rats were continuously treated with letrozole (p.o administration at 1 mg kg-1·day-1) and HFD for 21 days to establish the PCOS-IR model. Concurrently, metformin (200 mg kg-1·day-1) or LWDH Pills was orally administrated (1.2 or 3.6 g kg-1·day-1) to intervene disease progression. The ovarian pathology was evaluated by HE (hematoxylin-eosin) staining. The serum sexual hormones, follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, testosterone, progesterone and fasting insulin (FINS) were determined by radioimmunoassay. The protein expressions of IRS-1, PI3Kp85α, Akt and FoxO1a were analyzed by western blotting, while the mRNA levels of follicle-stimulating hormone receptor (FSHR) and Cyp19a1 in ovarian tissue were measured by qPCR. RESULTS: The upregulated phosphorylation of IRS-1 (S307), down-regulated phosphorylation of PI3Kp85α, Akt, and FoxO1a were significantly reversed by LWDH Pills (3.6 g kg-1·day-1) in PCOS-IR rats with up-regulated mRNA levels of FSHR and Cyp19a1 in ovary. Also, the index of insulin resistance was gradually adjusted to normal by LWDH Pills. The serum levels of FSH, estradiol, progesterone levels were significantly raised while LH, testosterone were reduced. The ovarian polycystic changes were alleviated while the atresia follicles were reduced. CONCLUSION: LWDH Pills therapy obviously improved the ovarian polycystic pathogenesis and regained the development of follicles via upregulating Cyp19a1, alleviated insulin resistance through acting on PI3K/Akt signaling pathway. These findings have provided scientific evidence for LWDH Pills to treat PCOS.

9.
Mol Ther ; 28(2): 572-586, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31732298

RESUMO

MicroRNA24-2 (miR24-2) is associated with human tumorigenesis; however, its molecular mechanisms are poorly understood. Herein, our findings demonstrate that miR24-2 promotes the proliferation ability in vitro and the tumorigenic ability in vivo in human liver cancer stem cells (hLCSCs). Mechanically, the miR24-2 targets for 3' UTR (2,627-2,648) of protein arginine methyltransferase 7 (PRMT7) inhibit the translational ability of prmt7 gene. Moreover, miR24-2 inhibits the di-/tri-methylation of histone H4 arginine 3 by reducing PRMT7 and then promotes the expression of Nanog via long noncoding RNA HULC. Notably, miR24-2 inhibits histone deacetylase HDAC3 through miR675, which promotes the acetylation of histone H4 at lysine 16. Subsequently, miR24-2 enhances the interaction between LC3 and ATG4 dependent on PI3K and triggers cellular autophagy. Strikingly, miR24-2 inhibits the degradation of pyruvate kinase M1 via autophagosome-P62 in hLCSCs. Furthermore, miR24-2 enhances the activity of Src by promoting the binding of PKM1 to the Src promoter regions in hLCSCs. In particular, our results also indicate that src gene determines the oncogenic functions of miR24-2. These results provided a valuable theoretical basis for the discovery of liver cancer therapeutic targets and diagnosis markers based on miR24-2.

10.
Dalton Trans ; 49(1): 89-94, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31815259

RESUMO

In this work, a new crystalline polyoxometalate-viologen hybrid, (Pbpy)(Me2NH2)3[PW11ZnO40] (1: Pbpy = 1,1'-[1,4-phenylenebis-(methylene)]bis(4,4'-bipyridinium)), has been synthesized. It showed efficient ultraviolet light detection ability with an obvious colour change from pale yellow to blue and fast response with ultraviolet intensity as low as 0.006 mW cm-2 in narrow-band UV regions. The POM-viologen-based film of 1 has also been readily prepared on quartz substrates using a drop casting method and could exhibit different levels of colour changes under sunlight irradiation at different local times on a sunny day, indicating its potential to be used as a portable device for solar ultraviolet light detection. Ultraviolet light detection is not only reflected in colour changes, but also accompanies the photoluminescence phenomenon. The fluorescence intensity decreased with the increase of UV intensity, and when irradiated with an ultraviolet xenon lamp (8 mW cm-2) for about 5 min, the fluorescence intensity was almost completely quenched. The compound has the potential to achieve fluorescence based UV probing. The powdered sample of compound 1 could also be deposited in paper simply by coating it with a solution of ethanol. The paper can be used as an inkless and erasable print medium, which was found to remain clear for 11 d in the dark under an ambient atmosphere and was also reusable when erased.

11.
Brain Lang ; 201: 104721, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31865263

RESUMO

Orthographic processing is a critical stage in visual word recognition. However, the white-matter pathways that support this processing are unclear, as prior findings might have been confounded by impure behavioral measures, potential structural reorganization of the brain, and limited sample sizes. To address this issue, we investigated the correlations between the integrity of 20 major tracts in the whole brain and the pure orthographic index across 67 patients with short-term brain damage. The integrity of the tracts was measured by the lesion volume percentage and the mean fractional anisotropy value. The orthographic index was calculated as the residual of the orthographic tasks after regressing out corresponding nonorthographic tasks and the orthographic factor from the principal component analysis (PCA) on the basis of four orthographic tasks. We found significant correlations associated with the left inferior longitudinal fasciculus (ILF), even after controlling for the influence of potential confounding variables. These observations strengthen evidence for the vital role of the left ILF in orthographic processing.

12.
Mol Carcinog ; 59(3): 281-292, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31872914

RESUMO

Medulloblastoma (MB) is the most common and deadliest brain tumor in children. Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a scaffolding protein and its oncogenic signaling is implicated in the progression of several cancers. However, the role of PELP1 in the progression of MB remains unknown. The objective of this study is to examine the role of PELP1 in the progression of MB. Immunohistochemical analysis of MB tissue microarrays revealed that PELP1 is overexpressed in the MB specimens compared to normal brain. Knockdown of PELP1 reduced cell proliferation, cell survival, and cell invasion of MB cell lines. The RNA-sequencing analysis revealed that PELP1 knockdown significantly downregulated the pathways related to inflammation and extracellular matrix. Gene set enrichment analysis confirmed that the PELP1-regulated genes were negatively correlated with nuclear factor-κB (NF-κB), extracellular matrix, and angiogenesis gene sets. Interestingly, PELP1 knockdown reduced the expression of NF-κB target genes, NF-κB reporter activity, and inhibited the nuclear translocation of p65. Importantly, the knockdown of PELP1 significantly reduced in vivo MB progression in orthotopic models and improved the overall mice survival. Collectively, these results suggest that PELP1 could be a novel target for therapeutic intervention in MB.

13.
Sci Total Environ ; 698: 134315, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31783453

RESUMO

Bioaerosol in the atmosphere plays a very important role in environment and public health. To forecast the bioaerosol concentration, the correlation between bioaerosol concentration and meteorological factors was discussed, and a Back Propagation (BP) neural network with Principal Component Analysis (PCA) method was utilized in this study. The proposed method works in three steps. The first step is to compute the correlation between bioaerosol concentration and meteorological factors, which consists of analyzing correlation and selecting meteorological factors applied to the study of forecast model. The second step is to use PCA analysis to reduce the dimensions of meteorological dataset. The third step is to use BP neural network, setting up, training BP neural network and proving the feasibility of forecast model included. The results of our model in forecasting bioaerosol concentration show 10.55% of average relative error, 2.80 pieces/L (pcs/L) of average absolute error, and 84.01 grade of forecast accuracy, providing a promising model for the forecasting of bioaerosol concentration.


Assuntos
Aerossóis/análise , Poluição do Ar/estatística & dados numéricos , Monitoramento Ambiental/métodos , Atmosfera , Conceitos Meteorológicos
14.
Nature ; 576(7786): 274-280, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31802000

RESUMO

Embryonal tumours with multilayered rosettes (ETMRs) are aggressive paediatric embryonal brain tumours with a universally poor prognosis1. Here we collected 193 primary ETMRs and 23 matched relapse samples to investigate the genomic landscape of this distinct tumour type. We found that patients with tumours in which the proposed driver C19MC2-4 was not amplified frequently had germline mutations in DICER1 or other microRNA-related aberrations such as somatic amplification of miR-17-92 (also known as MIR17HG). Whole-genome sequencing revealed that tumours had an overall low recurrence of single-nucleotide variants (SNVs), but showed prevalent genomic instability caused by widespread occurrence of R-loop structures. We show that R-loop-associated chromosomal instability can be induced by the loss of DICER1 function. Comparison of primary tumours and matched relapse samples showed a strong conservation of structural variants, but low conservation of SNVs. Moreover, many newly acquired SNVs are associated with a mutational signature related to cisplatin treatment. Finally, we show that targeting R-loops with topoisomerase and PARP inhibitors might be an effective treatment strategy for this deadly disease.

15.
Sleep Breath ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31832981

RESUMO

PURPOSE: To study and analyze the sleep quality and sleep structure of patients with vestibular migraine (VM). METHODS: In this cross-sectional case-control study, the Pittsburgh Sleep Quality Index (PSQI) questionnaire and polysomnography (PSG) were used to compare the clinical characteristics of sleep disorders in 49 patients with VM, 52 patients with migraine, and 54 controls. RESULTS: The VM, migraine, and control groups did not significantly differ in terms of age or sex. Compared with the migraine and control groups, the VM group had a higher incidence of poor sleep quality (χ2 = 36.618, p < 0.01) and greater severity of poor sleep quality (p < 0.01). Furthermore, the VM group showed reduced sleep efficiency (p < 0.01) and reduced proportions of REM and slow wave (N3) sleep (p ≤ 0.01). Conversely, sleep latency (p = 0.01) and REM latency (p = 0.04) were prolonged, and proportions of light sleep phases (N1, p < 0.05, and N2, p < 0.01) and the micro-arousal index (p = 0.03) were increased. The migraine group had significantly higher apnea hypopnea (AHI) and periodic leg movement (PLMI) indices than the VM group. CONCLUSION: We report an effect of VM on sleep structure and an association with migraine. Similar to migraine, VM affects the sleep regulation centers and causes structural sleep disorders.

16.
Mol Oncol ; 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31872963

RESUMO

The development of pulmonary metastasis is the leading cause of death in osteosarcoma (OS), which is the most common malignant bone tumor in children. We have previously reported that the tumor suppressor p27 (KIP1, CDKN1B) is frequently mislocalized to the cytoplasm of OS. However, its prognostic significance and metastatic mechanism are still elusive. Here, we show that cytoplasmic p27 significantly correlated with a higher metastatic status and poorer survival of OS patients (n = 136, P < 0.05), highlighting the clinical significance of p27 mislocalization in OS. Mechanistically, cytoplasmic p27 is co-immunoprecipitated with p21-activated kinase 1 (PAK1), which resulted in higher PAK1 phosphorylations, actin polymerization, and cell motility in p27-mislocalized OS cells. Silencing PAK1 expression in different p27-mislocalized OS cell lines decreased the migratory and adhesion abilities in vitro, as well as the development of pulmonary metastases in vivo. Similar PAK1-dependent motility was also observed in other p27-mislocalized cancer cell lines. In summary, our study suggests that cytoplasmic p27-mediated PAK1 activation is crucial for OS metastasis. A biomarker-guided targeted therapeutic approach for metastatic OS and other cancers harboring p27 mislocalization can be developed, where cytoplasmic p27 is used for risk stratification and PAK1 can be exploited as a potential therapeutic target.

17.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(11): 1064-1068, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31753085

RESUMO

OBJECTIVE: To investigate the risk factors for poor prognosis of neonatal bacterial meningitis. METHODS: A retrospective analysis was performed for the clinical data of 152 children with neonatal bacterial meningitis. According to their prognosis, they were divided into a good prognosis group with 122 children and a poor prognosis group with 30 children. The two groups were compared in terms of general status, initial symptoms, and laboratory findings, and the risk factors for poor prognosis were analyzed. RESULTS: Compared with the good prognosis group, the poor prognosis group had a significantly higher proportion of children with a very low birth weight, a peripheral blood white blood cell count (WBC) of <5×109/L or >20×109/L, a C-reactive protein level of >50 mg/L, a cerebrospinal fluid (CSF) WBC of >500×106/L, a CSF glucose level of <1 mmol/L, or a CSF protein level of >2 g/L, as well as significantly higher positive rates of blood culture and/or CSF culture, Gram-positive bacteria, and Streptococcus agalactiae (P<0.05). The multivariate logistic regression analysis showed that a CSF glucose level of <1 mmol/L and a CSF protein level of >2 g/L were independent risk factors for poor prognosis of neonatal bacterial meningitis. CONCLUSIONS: A CSF glucose level of <1 mmol/L and a CSF protein level of >2 g/L are risk factors for poor prognosis of neonatal bacterial meningitis.


Assuntos
Meningites Bacterianas , Criança , Humanos , Recém-Nascido , Contagem de Leucócitos , Prognóstico , Estudos Retrospectivos , Fatores de Risco
18.
Front Pediatr ; 7: 347, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31552203

RESUMO

Purpose: To evaluate effects on growth and infection rates of supplementing infant formula with the probiotic Lactobacillus paracasei ssp. paracasei strain F19 (F19) or bovine milk fat globule membrane (MFGM). Methods: In a double-blind, randomized controlled trial, 600 infants were randomized to a formula supplemented with F19 or MFGM, or to standard formula (SF). A breastfed group was recruited as reference (n = 200).The intervention lasted from age 21 ± 7 days until 4 months, and infants were followed until age one year. Results: Both experimental formulas were well tolerated and resulted in high compliance. The few reported adverse events were not likely related to formula, with the highest rates in the SF group, significantly higher than for the F19-supplemented infants (p = 0.046). Weight or length gain did not differ during or after the intervention among the formula-fed groups, with satisfactory growth. During the intervention, overall, the experimental formula groups did not have more episodes of diarrhea, fever, or days with fever than the breastfed infants. However, compared to the breastfed infants, the SF group had more fever episodes (p = 0.021) and days with fever (p = 0.036), but not diarrhea. Compared with the breastfed group, the F19-supplemented infants but not the other two formula groups had more visits/unscheduled hospitalizations (p = 0.015) and borderline more episodes of upper respiratory tract infections (p = 0.048). Conclusions: Both the MFGM- and F19-supplemented formulas were safe and well-tolerated, leading to few adverse effects, similar to the breastfed group and unlike the SF group. During the intervention, the MFGM-supplemented infants did not differ from the breastfed infants in any primary outcome.

19.
Pharmaceutics ; 11(9)2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31547272

RESUMO

In this study, a new kind of folic acid (FA)-conjugated and chitosan (CS)-coated poloxamer 407 (P407)/poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), FCPP NPs, were prepared, and further micro-encapsulated by carboxymethyl ß-glucan microcapsules (MCs) to produce a multifunctional system of NPs embedded in MCs (NEMs) for potential lung tumor-targeted delivery of gefitinib. The prepared gefitinib-loaded FCPP (GFB/FCPP) NPs showed a hydrodynamic diameter of 255.4 ± 14.5 nm and existed in an amorphous state. After encapsulation in carboxymethyl ß-glucan MCs, the GFB/FCPP-based NEMs (GFB/FCPP-NEMs) also exhibited a spherical morphology with a median diameter (d50) of around 2.2 µm. After hydration, GFB/FCPP- NEMs can quickly dissociate into its primary particles, GFB/FCPP NPs. Our in vitro drug release study revealed that these GFB/FCPP-NEMs exhibited a pH-responsive prolonged release property. In addition, the cellular uptake study demonstrated that FCPP-NEMs serve as an efficient carrier to enhance the delivery of the entrapped drug into the target lung tumor cells. Moreover, the GFB/FCPP-NEMs induced a superior cytotoxic effect compared with free gefitinib. The inhibitory concentration to achieve 50% cell death (IC50) of GFB/FCPP-NEMs in A549 cells was 3.82-fold lower than that of free gefitinib. According to these results, FCPP-NEMs hold a great potential as a multifunctional and high-performance biomaterial for lung tumor targeting delivery, pH-responsive sustained release, facilitated cellular uptake, and enhanced antitumor effect of antitumor drugs, like gefitinib.

20.
Cancer Cell ; 36(1): 51-67.e7, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31287992

RESUMO

Embryonal tumors with multilayered rosettes (ETMRs) are highly lethal infant brain cancers with characteristic amplification of Chr19q13.41 miRNA cluster (C19MC) and enrichment of pluripotency factor LIN28A. Here we investigated C19MC oncogenic mechanisms and discovered a C19MC-LIN28A-MYCN circuit fueled by multiple complex regulatory loops including an MYCN core transcriptional network and super-enhancers resulting from long-range MYCN DNA interactions and C19MC gene fusions. Our data show that this powerful oncogenic circuit, which entraps an early neural lineage network, is potently abrogated by bromodomain inhibitor JQ1, leading to ETMR cell death.

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