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1.
J Affect Disord ; 260: 557-568, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31539693

RESUMO

OBJECTIVE: This study mapped the topological configuration of the default mode network (DMN) in patients with depressive symptoms after acute ischemic stroke. METHODS: The study sample comprised 63 patients: 36 with poststroke depressive symptoms (PSD) and 37 without PSD matched according to age, gender and the severity of stroke. PSD was defined by a cutoff of ≥ 7 on the 15-item Geriatric Depression Scale (GDS). Resting-state functional magnetic resonance imaging (fMRI) was used to examine functional connectivity (FC) to reconstruct the DMN. Network based statistics estimated the FC differences of the DMN between the PSD and non-PSD groups. Graph theoretical approaches were used to characterize the topological properties of this network. RESULTS: The study sample mainly comprised patients with mild to moderate stroke. A widespread hyper-connected configuration of the functional DMN was characterized in PSD group. The orbital frontal, dorsolateral prefrontal, dorsal medial prefrontal and, ventromedial prefrontal corticis, the middle temporal gyrus and the inferior parietal lobule were the functional hubs related to PSD. The nodal topology in inferior parietal lobule and superior frontal gyrus, overlapping with dorsal medial prefrontal and, ventromedial prefrontal cortices, tended to be functionally integrated in patients with PSD. After False Discovery Rate correction, no significant difference between the PSD and non-PSD groups was found with respect to the global and nodal metrics of the DMN. However, the correlations between these altered network metrics and severity of PSD were lacking. LIMITATIONS: The diagnosis of PSD was based on the GDS score rather than established with a structured clinical interview. CONCLUSIONS: The DMN in PSD was functionally integrated and more specialized in some core hubs such as the inferior parietal lobule and dorsal prefrontal cortex. The configuration of the subnetwork like DMN may be more essential in the pathogenesis of PSD than single stroke lesions.

2.
Sci Total Environ ; : 134552, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31787280

RESUMO

Sulfonamide antibiotics are contaminants of emerging concern (CEC). These CECs raise considerable alarm because they are commonly present in water environments. Studies on the environmental existence of CECs in karst areas of Guilin (Southern China) have yet to be reported. Thus, this study aims to investigate the presence, temporal and spatial distributions of sulfonamides in surface water and groundwater of four major aquatic environments (i.e., aquafarm water, ditch water, wetland water, and groundwater) in the Huixian karst wetland system of Guilin. Furthermore, this study aims to determine the ecological and human health risks of individual sulfonamides and their mixtures. Ten sulfonamides (i.e., sulfadiazine, sulfapyridine, sulfamerazine, trimethoprim, sulfamethazine, sulfamethoxypyridazine, sulfachloropyridazine, sulfamethoxazole, sulfadimethoxine, and sulfaquinoxaline) were observed in the study area. The highest average concentrations of aquafarm water, ditch water, wetland water, and groundwater were those of sulfadiazine (48.24 µg/L), sulfamethoxypyridazine (1281.50 µg/L), sulfamethoxazole (51.14 µg/L), and sulfamethazine (20.06 µg/L), respectively. The potential ecological risks of the detected compounds were much higher in ditch water than in aquafarm water, wetland water, and groundwater. The most ecological risks were observed for sulfachloropyridazine with a risk quotient (RQ) reaching 335.5 to green algae and 152 to Daphnia magna in ditch water. Similarly, sulfachloropyridazine posed the highest ecological risks to green algae among the ten sulfonamides in aquafarm water (RQ = 3.39), wetland water (RQ = 2.98), and groundwater (RQ = 3.6). Human health risk for age groups<12 months was observed from sulfonamide in drinking groundwater. Ecological and human health risks caused by sulfonamide mixtures were larger than the individual risks. Overall, ecological and human health risks caused by sulfonamides were observed in the study area.

3.
Diagn Pathol ; 14(1): 132, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801557

RESUMO

BACKGROUND: MicroRNAs (miRNAs) have been reported to serve pivotal roles in tumorigenesis. This study sough to assess the expression and clinical significance of microRNA-1298 (miR-1298) in patients with non-small cell lung cancer (NSCLC), and explore the functional role of miR-1298 in tumorigenesis. METHODS: One hundred and twenty-one NSCLC patients were recruited in this study. The expression of miR-1298 was estimated using quantitative real-time PCR. Kaplan-Meier survival curves and Cox regression analysis were used to evaluate the prognostic value of miR-1298. Gain- and loss-of-function experiments were preformed to explore the biological function of miR-1298 in NSCLC cells. RESULTS: Expression levels of miR-1298 were downregulated in NSCLC tissues and cells compared with the corresponding normal controls. The decreased expression of miR-1298 was associated with patients' lymph node metastasis and TNM stage. The low expression of miR-1298 predicted poor overall survival and served as an independent prognostic indicator in NSCLC patients. According to the cell experiments, NSCLC cell proliferation, migration and invasion were inhibited by the overexpression of miR-1298. CONCLUSION: All the data indicated that the downregulation of miR-1298 predicts poor prognosis of NSCLC, and the overexpression of miR-1298 in NSCLC cells leads to inhibited tumorigenesis. The aberrant miR-1298 may serve as a novel biomarker and therapeutic target in NSCLC.

4.
Opt Express ; 27(22): 32349-32359, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31684449

RESUMO

Recently, ghost imaging has been attracting attention because its mechanism could lead to many applications inaccessible to conventional imaging methods. However, it is challenging for high-contrast and high-resolution imaging, due to its low signal-to-noise ratio (SNR) and the demand of high sampling rate in detection. To circumvent these challenges, we propose a ghost imaging scheme that exploits Haar wavelets as illuminating patterns with a bi-frequency light projecting system and frequency-selecting single-pixel detectors. This method provides a theoretically 100% image contrast and high-detection SNR, which reduces the requirement of high dynamic range of detectors, enabling high-resolution ghost imaging. Moreover, it can highly reduce the sampling rate (far below Nyquist limit) for a sparse object by adaptively abandoning unnecessary patterns during the measurement. These characteristics are experimentally verified with a resolution of 512×512 and a sampling rate lower than 5%. A high-resolution (1000×1000×1000) 3D reconstruction of an object is also achieved from multi-angle images.

5.
Bioorg Med Chem Lett ; : 126796, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31757669

RESUMO

Dysregulation of the ceramide transport protein CERT is associated to diseases such as cancer. In search for new CERT START domain ligands, N-dodecyl-deoxynojirimycin (N-dodecyl-DNJ) iminosugar was found to display, as a ceramide mimic, significant protein recognition. To reinforce the lipophilic interactions and strengthen this protein binding, a docking study was carried out in order to select the optimal position on which to introduce an additional O-alkyl chain on N-dodecyl-DNJ. Analysis of the calculated poses for three different regioisomers indicated an optimal calculated interaction pattern for N,O3-didodecyl-DNJ. The two most promising regioisomers were prepared by a divergent route and their binding to the CERT START domain was evaluated with fluorescence intensity (FLINT) binding assay. N,O3-didodecyl-DNJ was confirmed to be a new binder prototype with level of protein recognition in the FLINT assay comparable to the best known ligands from the alkylated HPA-12 series. This work opens promising perspectives for the development of new inhibitors of CERT-mediated ceramide trafficking.

6.
J Hazard Mater ; : 121402, 2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31668761

RESUMO

Crystal facets engineering and graphene hybridizing have been proved to be effective means to improve the photocatalytic activities of semiconductor photocatalysts in recent years. However, most of these efforts are concentrated in metal oxides. In the present study, crystal facets effect on the photocatalytic activity of metal sulfide NiS2 was studied for the first time. It was found that the {111}-faceted NiS2 nanocrystals showed improved photocatalytic activity in the degradation of various typical pollutants in water compared with {100}-faceted NiS2 nanocrystals. Moreover, through hybridizing with rGO nanosheets, the photocatalytic activity of the {111}-faceted NiS2 nanocrystals can be further improved, resulting in the complete degradation of heavy metal hexavalent chromium and organic dyes. The photocatalytic mechanism was studied in detail through theory calculation and experimental characterization. It was found that both the surface energies of Ni-terminated and S-terminated {111} facets were much higher than that of {100} facets, indicating that {111} facets were more active. Besides, rGO hybridizing can realize the effective separation of photogenerated electrons and holes. The results provide important guidance for the further development of efficient metal sulfide photocatalysts.

7.
Genes (Basel) ; 10(11)2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31739481

RESUMO

The root-knot nematode (RKN) is one of the most dangerous and widespread types of nematodes affecting tomatoes. There are few methods for controlling nematodes in tomatoes. Nature resistance genes (R-genes) are important in conferring resistance against nematodes. These genes that confer resistance to the RKN have already been identified as Mi-1, Mi-2, Mi-3, Mi-4, Mi-5, Mi-6, Mi-7, Mi-8, Mi-9, and Mi-HT. Only five of these genes have been mapped. The major problem is that their resistance breaks down at high temperatures. Some of these genes still work at high temperatures. In this paper, the mechanism and characteristics of these natural resistance genes are summarized. Other difficulties in using these genes in the resistance and how to improve them are also mentioned.

8.
Exp Cell Res ; : 111734, 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31770533

RESUMO

BACKGROUND: The molecular mechanisms of abnormal palatogenesis were investigated in this study. A key regulator, miR-106a-5p, and its target pathway were analyzed. OBJECTIVES: This research is trying to clarify the underlying mechanism of the modulation of miRNA transcription during the formation of cleft palate by 7T and 9.4T NMR metabolomic platforms. METHOD: Differentially expressed miRNAs and mRNAs were analyzed by microarray analysis and verified by qRT-PCR. The protein expression in TGFß signaling pathways were analyzed by Western Blotting. The relationship between miR-106a-5p and TGFß were analyzed by luciferase reporter assay. Cell apoptosis were analyzed by flow cytometer. And finally, the metabonomics were analyzed by NMR and multivariate data analysis models (MVDA). RESULTS: The expression of miR-106a-5p increased in cleft palatal tissue and negatively correlated with the protein level of Tgfbr2. The luciferase assay further proved that the tgfbr2 was a direct target of miR-106a-5p. In another aspect, miR-106a-5p increased apoptosis level in palatal mesenchymal cells, possibly because its inhibition of TGFß signaling pathway. Moreover, low cholesterol and choline levels with high citric acid and lipid levels were observed by 7T and 9.4T NMR metabonomic analysis, which inferred the disorder of cell membrane synthesis in cleft palate formation. Furthermore, transformation from choline to phosphatidylcholine regulated by miR-106a-5p was also disrupted, resulting in phosphatidic choline synthesis disorder and reduced cell membrane synthesis. CONCLUSIONS: The regulatory mechanism of cleft palate was studied at transcriptional and metabolomics levels, which may provide important information in understanding the primary cause of this abnormality.

9.
Math Biosci Eng ; 16(6): 8217-8242, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31698665

RESUMO

In this paper we have adapted a delayed dengue model to Zika. By assuming that the epidemic starts by a single infected individual entering a disease-free population at some initial time t0 we have used the least squares parameter estimation technique in R to estimate the initial time t0 using observed Zika data from Brazil as well as the transmission probabilities of Zika in Brazil between humans and mosquitoes and vice-versa. Different values of Aedes aegypti (A. aegypti) biting rate are used throughout the paper. We have estimated the value of the basic reproduction number for Zika in Brazil and calculated the expected number of cases of microcephaly in newborns as a result of women infected with Zika during pregnancy. We started off with a non-age-structured model then introduced age-structure into the model. However in reality seasonality, in particular temperature and rainfall, have a great impact on the population size of A. aegypti. Hence we repeat both the non-age-structured and age-structured analyses introducing seasonality into the A. aegypti birth function to model the effect of these environmental factors.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31702013

RESUMO

CONTEXT: Gonadotropin-releasing hormone analogues (GnRHa) and recombinant human growth hormone (rhGH) have been widely used to treat idiopathic central precocious puberty (CPP) or early and fast puberty (EFP). However, large-scale studies to evaluate the treatment effects on final adult height (FAH) are still lacking. OBJECTIVE: To assess the effects of long-term treatment for CPP/EFP on FAH and its main influencing factors. DESIGN AND SETTING: Retrospective, multi-center observational study from 1998-2017. PARTICIPANTS: Four hundred forty-eight Chinese girls with CPP/EFP received GnRHa and rhGH treatment (n=118), GnRHa alone (n=276), or no treatment (n=54). MAIN OUTCOME MEASURES: FAH, target height (Tht), and predictive adult height (PAH). RESULTS: The height gain (FAH-PAH) was significantly different among the GnRHa and rhGH treatment, GnRHa alone, and no treatment groups (p<0.05; 9.51±0.53, 8.07±0.37, and 6.44±0.91 cm, respectively). The genetic height gain (FAH-Tht) was 4.0±0.5 cm for the GnRHa+rhGH group and 2.0±0.27 cm for the GnRHa group, while the control group reached their Tht. In addition, five critical parameters derived from PAH, bone age, and Tht, showed excellent performance in predicting which patients could gain ≥5 cm (FAH-PAH), and this was further validated using an independent study. CONCLUSIONS: The overall beneficial effect of GnRHa+rhGH or GnRHa on FAH was significant. The control group also reached their genetic target height. Clinicians are recommended to consider both the potential gains in height and the cost of medication.

11.
Medicine (Baltimore) ; 98(46): e17849, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725625

RESUMO

BACKGROUND: Although some studies had been published, it was more controversial on the superiority of decompression alone (D) and decompression with fusion (F) for the treatment of lumbar spinal stenosis (LSS) recently, especially newest articles with different opinions. A meta-analysis was performed to compare efficacy on D and F for LSS regardless of degenerative spondylolisthesis (DS) with randomized controlled trials (RCTs). METHODS: The databases include PUBMED/MEDLINE, EMBASE, Cochrane Library, and Web of Science from January 1970 to December 2018. The information of screened studies included demographics, clinical outcomes, and secondary measures, then data synthesis and meta-analysis were progressed. Subgroup analysis was stratified by DS and follow-up time (36 months). Continuous variables and dichotomous variables were respectively reported as weighted mean difference and odds ratios (ORs). The strength of evidence was evaluated by the grades of recommendation, assessment, development, and evaluation (GRADE) system. RESULTS: Nine RCTs met inclusion criteria with a total of 857 patients (367 were in D group and 490 were in F group). There were no statistical difference in visual analog scale changes on back and leg pain between D and F group (mean difference [MD] = -0.03, 95% confidence interval [CI] [-0.38, 0.76], z = 0.08, P = .94; MD = 0.11, 95% CI [-1.08, 1.30], z = 0.18, P = .86, respectively); patients' satisfaction was of no difference between the 2 groups, together with the change of the Oswestry disability index and European quality of life-5 dimensions (P > .05). There were no difference in the rate of complication (P = .50) and reoperation (P = .11) while a statistical significance of longer operation duration (P < .0001), more blood loss (P = .004) but amazing lower rate of adjacent segment degenerative/disease (ASD) (OR = 2.35, P = .02) in F group. The subgroup analysis on DS showed that basically all measures were in consistency with meta-analysis. There was a higher reoperation rate in middle-to-long term (>36 months) in D group and ASD was the most seasons of reoperation no matter the follow-up time. According to the GRADE system, the grade of this meta-analysis was of "High" quality. CONCLUSION: F group has no better clinical results than D alone in LSS, regardless of DS and follow-up. The conclusion is of "High" quality and the grade strength of recommendation was "Strong."

12.
Molecules ; 24(22)2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31726738

RESUMO

Indigo naturalis (IN) is a traditional Chinese medicine, named Qing-Dai, which is extracted from indigo plants and has been used to treat patients with inflammatory bowel disease (IBD) in China and Japan. Though there are notable effects of IN on colitis, the mechanisms remain elusive. Regarding the significance of alterations of intestinal flora related to IBD and the poor water solubility of the blue IN powder, we predicted that the protective action of IN on colitis may occur through modifying gut microbiota. To investigate the relationships of IN, colitis, and gut microbiomes, a dextran sulfate sodium (DSS)-induced mice colitis model was tested to explore the protective effects of IN on macroscopic colitis symptoms, the histopathological structure, inflammation cytokines, and gut microbiota, and their potential functions. Sulfasalazine (SASP) was used as the positive control. Firstly, because it was a mixture, the main chemical compositions of indigo and indirubin in IN were detected by ultra-performance liquid chromatography (UPLC). The clinical activity score (CAS), hematoxylin and eosin (H&E) staining results, and enzyme-linked immunosorbent assay (ELISA) results in this study showed that IN greatly improved the health conditions of the tested colitis mice, ameliorated the histopathological structure of the colon tissue, down-regulated pro-inflammatory cytokines, and up-regulated anti-inflammatory cytokines. The results of 16S rDNA sequences analysis with the Illumina MiSeq platform showed that IN could modulate the balance of gut microbiota, especially by down-regulating the relative quantity of Turicibacter and up-regulating the relative quantity of Peptococcus. The therapeutic effect of IN may be closely related to the anaerobic gram-positive bacteria of Turicibacter and Peptococcus. The inferred metagenomes from 16S data using PICRUSt demonstrated that decreased metabolic genes, such as through biosynthesis of siderophore group nonribosomal peptides, non-homologous end-joining, and glycosphingolipid biosynthesis of lacto and neolacto series, may maintain microbiota homeostasis during inflammation from IN treatment in DSS-induced colitis.

13.
Drug Metab Dispos ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31704713

RESUMO

Glutathione (GSH) has been reported to be closely related to various diseases of central nervous system (CNS), yet its authentic active ingredients and action sites are still unclear. In the present study, oral exogenous GSH was first proved to significantly alleviate ischemic brain injury, but it was inconsistent with its low bioavailability and blood-brain barrier (BBB) permeability. In order to find out the exposure of GSH-derived ingredients, including GSH, cysteine (CYS), glutamate (Glu), glycine (GLY), CYS-GLY and γ-Glutamylcysteine (γ-GC) were systematically studied both in vitro and in vivo. The outcomes demonstrated that oral GSH could not only increases the GSH and CYS levels in rat striatum and cortex, but also can decrease the rise of intracerebral Glu concentration caused by ischemia/reperfusion (I/R) surgery. Then the influence of GSH on BBB was investigated via measuring IgG leakage, intracerebral endotoxin and tight junction proteins. All indicators showed that GSH-dosing can repair the destroyed BBB. This should be noted that oral GSH greatly enhances the exposure of GSH, CYS, CYS-GLY and γ-GC in rat duodenum, jejunum, ileum and colon. Accumulating evidence reveals a close linkage of brain injury and gastrointestinal dysfunction. Our findings further suggested that oral GSH significantly improves intestinal inflammatory damage and barrier disruption. In conclusion, oral GSH can have a direct therapeutic role in brain injury by stabilizing intracerebral levels of GSH, CYS and Glu. It can also play an indirect therapeutic role by enhancing the intestinal exposure of GSH, CYS, CYS-GLY, γ-GC and improving intestinal barrier disruptions. SIGNIFICANCE STATEMENT: The authentic active ingredients and action sites of exogenous GSH in the treatment of ischemic brain injury are still unclear. We uncovered that oral exogenous GSH not only stabilizes intracerebral levels of GSH, CYS and Glu to act on brain injury directly, but also can exert an indirect therapeutic role by improving intestinal barrier disruptions. These findings have great significance for revealing the therapeutic effect of GSH on ischemic brain injury and promoting its further development and clinical application.

14.
J Am Heart Assoc ; 8(22): e013448, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31694442

RESUMO

Background Behavioral dysexecutive syndrome (BDES) is a common phenomenon following stroke. To date, research has focused mainly on individual behavioral symptoms rather than a more comprehensive characterization of goal-directed behavior in stroke survivors. This cross-sectional study evaluated the prevalence and clinical correlates of BDES in Hong Kong stroke survivors. Methods and Results A total of 369 stroke survivors were recruited from a regional hospital at 3 months after their index stroke. Patients' demographic and clinical characteristics were extracted from a comprehensive stroke database. BDES was measured with the Chinese version of the Dysexecutive Questionnaire. Four neurocognitive batteries assessed domains of cognitive executive functions. The prevalence of BDES 3 months poststroke was 18.7%. At that time point, the Hospital Anxiety Depression Scale and Mini-Mental State Examination scores and the presence of depression were significant predictors of BDES in a multivariate logistic regression analysis. These parameters remained significant predictors of the Dysexecutive Questionnaire score in a linear stepwise regression analysis and together accounted for 28.5% of the variance. Current depression was predictive of the Dysexecutive Questionnaire score in patients with BDES, with a variance of 9.7%. Furthermore, compared with the non-BDES group, patients with BDES exhibited poor performance-based executive function in the Chinese version of the Frontal Assessment Battery and color trails, arrow, and category fluency tests. Conclusions Symptoms of anxiety, current depression, and global cognitive function may be independent predictors of the presence and severity of BDES 3 months poststroke. Stroke survivors with BDES exhibit poor executive functioning, including goal maintenance and semantic memory.

15.
Plant Cell Environ ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675439

RESUMO

The endophytic fungus Falciphora oryzae was initially isolated from wild rice (Oryza granulata) and colonizes many crop species and promotes plant growth. However, the molecular mechanisms underlying F. oryzae-mediated growth promotion are still unknown. We found that F. oryzae was able to colonize Arabidopsis thaliana. The most dramatic change after F. oryzae inoculation was observed in the root architecture, as evidenced by increased lateral root growth but reduced primary root length, similar to the effect of auxin, a significant plant growth hormone. The expression of genes responsible for auxin biosynthesis, transport, and signalling was regulated in Arabidopsis roots after F. oryzae cocultivation. Indole derivatives were detected at significantly higher levels in liquid media after cocultivation compared with separate cultivation of Arabidopsis and F. oryzae. Consistently, the expression of indole biosynthetic genes was highly upregulated in F. oryzae upon treatment with Arabidopsis exudates. Global analysis of Arabidopsis gene expression at the early stage after F. oryzae cocultivation suggested that signals were exchanged to initiate Arabidopsis-F. oryzae interactions. All these results suggest that signalling molecules from Arabidopsis roots are perceived by F. oryzae and induce the biosynthesis of indole derivatives in F. oryzae, consequently stimulating Arabidopsis lateral root growth.

16.
J Nanobiotechnology ; 17(1): 113, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699100

RESUMO

BACKGROUND: Synergistic therapy of tumor is a promising way in curing cancer and in order to achieve effective tumor therapy with real-time drug release monitoring, dynamic cellular imaging and antitumor activity. RESULTS: In this work, a polymeric nanoparticle with Forster resonance energy transfer (FRET) effect and chemo-photodynamic properties was fabricated as the drug vehicle. An amphiphilic polymer of cyclo(RGDfCSH) (cRGD)-poly(ethylene glycol) (PEG)-Poly(L-histidine) (PH)-poly(ε-caprolactone) (PCL)-Protoporphyrin (Por)-acting as both a photosensitizer for photodynamic therapy (PDT) and absorption of acceptor in FRET was synthesized and self-assembled into polymeric nanoparticles with epirubicin (EPI)-acting as an antitumor drug for chemotherapy and fluorescence of donor in FRET. Spherical EPI-loaded nanoparticles with the average size of 150 ± 2.4 nm was procured with negatively charged surface, pH sensitivity and high drug loading content (14.9 ± 1.5%). The cellular uptake of EPI-loaded cRGD-PEG-PH-PCL-Por was monitored in real time by the FRET effect between EPI and cRGD-PEG-PH-PCL-Por. The polymeric nanoparticles combined PDT and chemotherapy showed significant anticancer activity both in vitro (IC50 = 0.47 µg/mL) and better therapeutic efficacy than that of free EPI in vivo. CONCLUSIONS: This work provided a versatile strategy to fabricate nanoassemblies for intracellular tracking of drug release and synergistic chemo-photodynamic therapy.

17.
J Cell Biochem ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31674056

RESUMO

Recently, microRNAs (miRNAs) receive more attention due to their role in the pathogenesis of malignancies. Retinoblastoma (RB) is the most serious and harmful malignant tumor in infants and young children with eye diseases, which often endangers the lives of children. This study was designed to determine how miR-598 is involved in RB progression. In this study, quantitative reverse transcription-polymerase chain reaction, Western blot, dual-luciferase reporter, Cell Counting Kit-8, and Transwell assays were adopted to detect miR-598 expression and function in RB. The decreased expression of miR-598 was identified in RB. Overexpression of miR-598 suppressed the viability and metastasis of RB cells. Further, E2F transcription factor 1 (E2F1) is verified as a direct target of miR-598. Furthermore, E2F1 recovered miR-598-mediated-inhibition of cell viability and metastasis in RB. In addition, miR-598 was found to promote cell apoptosis and inactivate the protein kinase B (AKT) pathway in RB. miR-598 suppressed RB cell viability and metastasis through inhibiting E2F1 and inactivating AKT pathway, which may provide a new perspective for RB treatment.

18.
Cancer Med ; 2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31679184

RESUMO

With the growing use of immune checkpoint inhibitors (ICIs), case reports of rare yet life-threatening pituitary-adrenal dysfunctions, particularly for hypopituitarism, are increasingly being published. In this analysis, we focus on these events by including the most recent publications and reports from early phase I/II and phase III clinical trials and comparing the incidence and risks across different ICI regimens. PubMed, Embase, and the Cochrane Library were systematically searched from inception to April 2019 for clinical trials that reported on pituitary-adrenal dysfunction. The rates of events, odds ratios (ORs), and 95% confidence intervals (CIs) were obtained using random effects meta-analysis. The analyses included data from 160 trials involving 40 432 participants. The rate was 2.43% (95% CI, 1.73%-3.22%) for all-grade adrenal insufficiency and 3.25% (95% CI, 2.15%-4.51%) for hypophysitis. Compared with the placebo or other therapeutic regimens, ICI agents were associated with a higher incidence of serious-grade adrenal insufficiency (OR 3.19, 95% CI, 1.84 to 5.54) and hypophysitis (OR 4.77, 95% CI, 2.60 to 8.78). Among 71 serious-grade hypopituitarism instances in 12 336 patients, there was a significant association between ICIs and hypopituitarism (OR 3.62, 95% CI, 1.86 to 7.03). Substantial heterogeneity was noted across the studies for the rates of these events, which in part was attributable to the different types of ICIs and varied phases of the clinical trials. Although the rates of these events were low, the risk was increased following ICI-based treatment, particularly for CTLA-4 inhibitors, which were associated with a higher incidence of pituitary-adrenal dysfunction than PD-1/PD-L1 inhibitors.

19.
Int J Mol Sci ; 20(21)2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31717797

RESUMO

In the present study, a series of 4-acyloxy robustic acid derivatives were synthesized and characterized for evaluation of their anti-cancer activity. The structures of these derivatives were elucidated by mass spectra (MS) nuclear magnetic resonance spectra (NMR). The single-crystal X-ray diffraction structure of one of these compounds was obtained, for further validation of the target compound structures. The anticancer activities of the target products were evaluated against human leukemic cells HL-60, human non-small cell lung carcinoma cells A-549, human hepatic carcinoma cells SMMC-7721, human hepatocellular carcinoma cells HepG2, and human cervical carcinoma cells Hela. Three compounds among them exhibited potent in-vitro cytotoxicity and excellent DNA topoisomerase I inhibitory activity, even at 0.1 mM concentrations. The most noteworthy observation was the minor toxicity of two of these compounds to normal cells, with an activity similar to the positive control in cancerous cells. A Surflex-Dock docking study was performed to investigate the topoisomerase I activity of all compounds. Of all the other compounds, the most sensitive compound was selected for further investigation of its effect on apoptosis induction and cell cycle regulation in HL-60 cells. Our results suggest that the anticancer effects of these compounds can be attributed to their pharmacological effects on topoisomerase I, cell apoptosis, and cell cycle. These findings suggest that robustic acid derivatives could be used as potential antitumor drugs.

20.
J Hazard Mater ; : 121685, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31776088

RESUMO

Disinfection by-products (DBPs) are generated during chlorination of drinking water. Previous studies demonstrate that DBPs are cytotoxic, genotoxic and associated with an increased risk of human cancer. However, the molecular basis of DBPs-induced toxic effects remains unclear. Here, we chlorinated samples of algal-derived organic matter (AOM) and sediment organic matter (SOM) from a local drinking water reservoir. Chemical properties, toxicities and transcriptomic profiles of human Caco-2 cell exposed to AOM and SOM were compared before and after chlorination. We analyzed chlorination-caused distinct gene expression patterns between AOM and SOM, and identified a set of 22 differentially expressed genes under chlorination of AOM that are different from chlorinated SOM. Consequent network analysis indicates that differential CYP1A1, CYP1B1, ID1 and ID2 are common targets of the upstream regulators predicted in the AOM group, but not the SOM group. Through experimental validation and data integration from previous reports related to DBPs or environmental stressors, we found that CYP1A1 and CYP1B1 are specifically up-regulated after chlorinating AOM. Our study demonstrates that the two CYP1 genes likely act as novel biomarkers of AOM derived DBPs, and this would be helpful for testing drinking water DBPs toxicity and further monitoring drinking water safety.

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