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1.
Comput Math Methods Med ; 2020: 7984565, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33133226

RESUMO

Objective: This paper was aimed at investigating the effects of bronchoalveolar lavage (BAL) with ambroxol hydrochloride (AH) on treating pulmonary infection and on serum proinflammatory cytokines and oxidative stress responses in patients with cerebral infarction (CI). Methods: One hundred and two patients with cerebral infarction complicated with pulmonary infection (CIPI) who were treated in our hospital were enrolled as research objects, divided into an observation group (52 cases; AH combined with BAL) and a control group (50 cases; single AH) based on therapeutic schemes. They were compared in terms of the therapeutic effect and pre- and posttreatment serum inflammatory cytokines, pulmonary function, and serum indices of oxidative stress. Their adverse reactions during treatment were also recorded and compared. Results: The therapeutic effect in the observation group was remarkably better than that in the control group (P < 0.05). After treatment, the serum inflammatory cytokines, pulmonary function, and serum indices of oxidative stress were remarkably improved in the two groups (P < 0.05), but the improvement was remarkably better in the observation group (P < 0.05). The differences were not significant in intratreatment adverse reactions between the two groups (P > 0.05). Conclusion: For CIPI patients, BAL with AH has a better therapeutic effect and higher safety and can control the patients' systemic inflammatory responses and oxidative stress responses, so it is worthy of further promotion in clinical practice.

2.
Mol Neurobiol ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33219486

RESUMO

Recent genetic studies clearly indicate that variants in several lysosomal genes act as risk factors for idiopathic Parkinson's disease (PD). Variants in the co-activator of glucocerebrosidase gene (GBA) and the four active saposins (Sap A-D) which are encoded by the prosaposin gene (PSAP) are of particular interest; however, their genetic roles in PD are unknown. Whole-exome sequencing and Sanger sequencing were used to assess the genetic etiology of 400 autosomal dominant inherited PD (ADPD) and 300 sporadic PD (SPD) patients. Variants from public databases, including Genome Aggregation Database-East Asian (GnomAD_EAS) and Chinese Millionome Database (CMDB), were used as control groups. Burden analysis based on gene and domains level were performed to investigate the role of rare PSAP variants in PD. Six rare and likely pathogenic variants, located in the Sap A-D domains, were identified and accounted for 0.75% (3/400) of ADPD and 1.33% (4/300) of SPD in the Chinese population. Based on the gene or domain, burden analysis showed that damaging missense variants in SapC had statistical significance on the risk of developing PD. Interestingly, rs4747203, an intronic variant potentially linked to PSAP expression, was associated with reduced risk for PD (p = 8.6e-7 in GnomAD EAS and p = 0.002 in Chinese). Clinically, patients carrying the likely pathogenic variants presented typical PD motor symptoms and responded well to levodopa treatment. Six out of seven patients carrying the likely pathogenic variants of PSAP presented slow disease progression, and none of the patients developed cognitive impairment. Our study expands the spectrum of mutations associated with the risk of developing PD and enhances the understanding of the relationship of the clinical phenotype of PD with PSAP variants.

3.
Int Health ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33210133

RESUMO

BACKGROUND: This study aimed to identify characteristics and trends in insurance-reimbursed inpatient care (NRIC) for gastric and oesophageal cancers and inform evaluation of medical systems reform. METHODS: The study extracted routinely collected records of claims for reimbursement from the New Rural Cooperative Medical System (NRCMS) in Anhui Province, China and performed descriptive and regression discontinuity analysis. RESULTS: From 2013 to 2017, NRIC in terms of person-time per million people (pmp) increased 5.60 and 20.62 times for gastric and oesophageal cancers, respectively. Total expense per episode for gastric and oesophageal cancers increased from 1130.25 and 22 697.99 yuan to 12 514.98 and 24 639.37 yuan, respectively. The ratio of out-of-pocket expenses per inpatient care episode to annual disposable income per capita was 0.43 for gastric cancer and 0.91 for oesophageal cancer and decreased by 0.17 and 0.47, respectively. Regression discontinuity modelling revealed that, when controlled for disposable income, illiteracy rate and months from start time, the treatment variable was significantly associated with person-times of NRIC pmp (ß=0.613, p=0.000), length of stay per 105 people (ß=-52.990, p=0.000) and total expenses per NRIC episode (ß=2.431, p=0.000). CONCLUSIONS: The study period witnessed substantial achievements in benefits to patients, inpatient care efficiency and equity. These achievements may be attributed mainly to the recent reforms launched in Anhui province, China.

4.
JAMA Pediatr ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33074282

RESUMO

Importance: The standard of care for refeeding inpatients with anorexia nervosa, starting with low calories and advancing cautiously, is associated with slow weight gain and protracted hospital stay. Limited data suggest that higher-calorie refeeding improves these outcomes with no increased risk of refeeding syndrome. Objective: To compare the short-term efficacy, safety, and cost of lower-calorie vs higher-calorie refeeding for malnourished adolescents and young adults with anorexia nervosa. Design, Setting, and Participants: In this multicenter randomized clinical trial with prospective follow-up conducted at 2 inpatient eating disorder programs at large tertiary care hospitals, 120 adolescents and young adults aged 12 to 24 years hospitalized with anorexia nervosa or atypical anorexia nervosa and 60% or more of median body mass index were enrolled from February 8, 2016, to March 7, 2019. The primary analysis was a modified intent-to-treat approach. Interventions: Higher-calorie refeeding, beginning at 2000 kcal/d and increasing by 200 kcal/d vs lower-calorie refeeding, beginning at 1400 k/cal and increasing by 200 kcal every other day. Main Outcomes and Measures: Main outcomes were end-of-treatment outcomes; the primary end point of this trial will be clinical remission over 12 months. Short-term efficacy was defined a priori as time to restore medical stability in the hospital, measured by the following 6 indices: 24-hour heart rate of 45 beats/min or more, systolic blood pressure of 90 mm Hg or more, temperature of 35.6 °C or more, orthostatic increase in heart rate of 35 beats/min or less, orthostatic decrease in systolic blood pressure of 20 mm Hg or less, and 75% or more of median body mass index for age and sex. The prespecified safety outcome was incidence of electrolyte abnormalities; cost efficacy was defined as savings associated with length of stay. Results: Because 9 participants withdrew prior to treatment, the modified intention-to-treat analyses included 111 participants (93%; 101 females [91%]; mean [SD] age, 16.4 [2.5] years). Higher-calorie refeeding restored medical stability significantly earlier than lower-calorie refeeding (hazard ratio, 1.67 [95% CI, 1.10-2.53]; P = .01). Electrolyte abnormalities and other adverse events did not differ by group. Hospital stay was 4.0 days shorter (95% CI, -6.1 to -1.9 days) among the group receiving higher-calorie refeeding, which was associated with a savings of $19 056 (95% CI, -$28 819 to -$9293) in hospital charges per participant. Conclusions and Relevance: In the first randomized clinical trial in the US to compare refeeding approaches in patients with anorexia nervosa and atypical anorexia nervosa, higher-calorie refeeding demonstrated short-term efficacy with no increase in safety events during hospitalization. Trial Registration: ClinicalTrials.gov Identifier: NCT02488109.

6.
Histol Histopathol ; : 18266, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33006132

RESUMO

BACKGROUND: Sevoflurane is widely used as an inhalational anesthetic in clinical practice. However, sevoflurane can cause cytotoxicity and induce learning capacity decline in patients. A previous publication indicated that miR-204-5p might have a close relationship with sevoflurane-induced neurotoxicity. When exposed to sevoflurane, the expression of miR-204-5p in neonatal hippocampus of rats was significantly increased. Hence, we aimed to investigate the role of miR-204-5p in sevoflurane-induced neurotoxicity using a mouse hippocampal neuronal cell line (HT22). METHODS: The levels of miR-204-5p in HT22 cells were detected by RT-qPCR. In addition, the effects of miR-204-5p on cell viability, apoptosis and proliferation were evaluated by CCK-8, flow cytometric, and immunofluorescence assay, respectively. Western blotting was used to detect expressions of Bax, Bcl-2, active caspase 3, BDNF, TrkB, p-TrkB, Akt and p-Akt in HT22 cells. ELISA assay was used to examine the levels of total superoxide dismutase (SOD), reduced glutathione (GSH), malondialdehyde (MDA) and reactive oxygen species (ROS) in cells. Meanwhile, the dual luciferase reporter system assay was employed to explore the interaction of miR-204-5p and BDNF in cells. RESULTS: The level of miR-204-5p was increased in sevoflurane-treated HT22 cells. Moreover, downregulation of miR-204-5p inhibited sevoflurane-induced apoptosis and promoted cell proliferation by upregulating the proteins of Bcl-2 and downregulating the expressions of Bax and active caspase-3 in HT22 cells. In addition, inhibition of miR-204-5p alleviated sevoflurane-induced oxidative injuries in HT22 cells via decline of ROS and MDA and upregulation of SOD and GSH. Furthermore, bioinformatics and dual luciferase assay demonstrated that miR-204-5p can inhibit the TrkB/Akt pathway by targeting BDNF. CONCLUSION: Our findings indicated that downregulation of miR-204-5p can decrease oxidative status in HT22 cells and alleviate sevoflurane-induced cytotoxicity through stimulating the BDNF/TrkB/Akt pathway. Therefore, miR-204-5p might be a potential biomarker and therapeutic target for the treatment of sevoflurane-induced neurotoxicity.

7.
Genes (Basel) ; 11(10)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33007888

RESUMO

To investigate the effect of light intensity on flavonoid biosynthesis, grapevine calluses were subjected to high light (HL, 250 µmol m-2 s-1) and dark (0 µmol m-2 s-1) in comparison to 125 µmol m-2 s-1 under controlled conditions (NL). The alteration of flavonoid profiles was determined and was integrated with RNA sequencing (RNA-seq)-based transcriptional changes of the flavonoid pathway genes. Results revealed that dark conditions inhibited flavonoid biosynthesis. Increasing light intensity affected flavonoids differently-the concentrations of flavonols and anthocyanins as well as the expressions of corresponding genes were less affected, whereas flavan-3-ol concentrations were predominantly increased, which caused enhanced trans-flavan-3-ol concentrations. Moreover, genes encoding leucoanthocyanidin reductase (LAR) exhibited different response patterns to light intensity changes-VviLAR1 expression increased with an increased light intensity, whereas VviLAR2 expression was insensitive. We further confirmed that the known transcription factors (TFs) involved in regulating flavan-3-ol biosynthesis utilized VviLAR1 as a target gene in grapevine calluses. In addition, VviLAR1 promoter activity was more sensitive to light intensity changes than that of VviLAR2 as determined using a transgenic Arabidopsis leaf system. These results suggested that light intensity had the most prominent effect on trans-flavan-3-ols in grapevine calluses and demonstrated that the two LAR genes had different response patterns to light intensity changes.

8.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 1485-1488, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018272

RESUMO

The susceptibility-based positive contrast MR technique was applied to estimate arbitrary magnetic susceptibility distributions of the metallic devices using a kernel deconvolution algorithm with a regularized L-1 minimization. Previously, the first-order primal-dual (PD) algorithm could provide a faster reconstruction time to solve the L-1 minimization, compared with other methods. Here, we propose to accelerate the PD algorithm of the positive contrast image using the multi-core multi-thread feature of graphics processor units (GPUs). The some experimental results showed that the GPU-based PD algorithm could achieve comparable accuracy of the metallic interventional devices in positive contrast imaging with less computational time. And the GPU-based PD approach was 4~15 times faster than the previous CPU-based scheme.Clinical Relevance-This can estimate arbitrary magnetic susceptibility distributions of the metallic devices with the processing efficacy of 4~15 times faster than before.


Assuntos
Algoritmos , Meios de Contraste , Imagem por Ressonância Magnética , Software
9.
Am J Health Promot ; : 890117120969057, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33111530

RESUMO

PURPOSE: Evaluate associations of adolescents' beverage marketing receptivity with sugar-sweetened beverage (SSB) perceived harm and intake. DESIGN: School-based cross-sectional health behavior survey. SETTING: Seven rural schools in California, 2019-2020. SUBJECTS: 815 student participants in grades 9 or 10. MEASURES: Participants viewed 6 beverage advertisement images with brand obscured, randomly selected from a larger pool. Ads for telecommunications products were an internal control. Receptivity was a composite of recognizing, liking, and identifying the displayed brand (later categorized: low, moderate, high). Weekly SSB servings were measured with a quantitative food frequency questionnaire and perceived SSB harm as 4 levels ("no harm" to "a lot"). ANALYSIS: Outcomes SSB intake (binomial regression) and perceived harm (ordered logistic regression) were modeled according to advertisement receptivity (independent variable), with multiple imputation, school-level clustering, and adjustment for presumed confounders (gender, age, screen time, etc.). RESULTS: In covariable-adjusted models, greater beverage advertisement receptivity independently predicted higher SSB intake (ratio of SSB servings, high vs. low receptivity: 1.48 [95% CI: 1.15, 1.89]) and lower perceived SSB harm (odds ratio, high vs. low receptivity: 0.59 [0.40, 0.88]). Perceived SSB harm was inversely associated with SSB intake. CONCLUSION: Beverage advertisement receptivity was associated with less perceived SSB harm and greater SSB consumption in this population. Policy strategies, including marketing restrictions or counter-marketing campaigns could potentially reduce SSB consumption and improve health.

10.
BMC Ophthalmol ; 20(1): 432, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33115419

RESUMO

BACKGROUND: At present, patients with ocular myasthenia gravis (OMG) are typically treated with systemic drugs. We investigated the use of dexamethasone injected in the peribulbar region or extraocular muscle to treat patients with OMG. METHODS: Patients with OMG were given dexamethasone via peribulbar injection or direct injection into the main paralyzed extraocular muscles, once a week, for 4-6 weeks. The severity of diplopia, blepharoptosis, eye position, and eye movement were evaluated before and after treatment. The duration of follow-up time was ≥6 months. RESULTS: Among the 14 patients with OMG who received this treatment, mean age was 38.7 ± 29.7 years. After treatment, symptoms were relieved in 12 patients (85.7%), 1 patient (7.1%) had partial response to treatment, and 1 patient (7.1%) had no response. Two patients (14.2%) experienced symptom recurrence during the follow-up period. CONCLUSIONS: Dexamethasone peribulbar or extraocular muscle injection is effective in the treatment of patients with OMG and may replace systemic drug therapy. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000038863 , October 7, 2020.Retrospectively registered.

11.
Int Immunopharmacol ; 89(Pt B): 107066, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33059199

RESUMO

Spontaneous abortion (SA) is a common pregnancy failure, but the cause of numerous cases remains unexplained. Decidual immune cells (DICs)-mediated cytokine microenvironment is involved in pregnancy and regulated by many microRNAs, but whether microRNA-146a-5p (miR-146a) regulate the decidual cytokine microenvironment and the potential mechanisms in unexplained SA pathogenesis have rarely been reported. In this study, the levels of cytokines and miR-146a in healthy and unexplained SA deciduae were first investigated, and the correlation between them was analyzed. Then, the effect of miR-146a inhibitor on cytokines was assessed in healthy deciduae-derived DICs. Third, the downstream targets and related molecular mechanisms of miR-146a were analyzed by bioinformatics, and the levels of the predicted targets in deciduae were assessed, followed by the correlation analysis between the levels of miR-146a and the targets. Finally, the effect of miR-146a on the predicted targets and inflammatory cytokines was validated in unexplained SA deciduae-derived DICs. As a result, decreased miR-146a correlated with the cytokine disorder in unexplained SA deciduae, and inhibition of miR-146a promoted pro-inflammatory response in healthy deciduae-derived DICs. One hundred four target genes and related molecular mechanisms of miR-146a were predicted, among which the toll-like receptor (TLR) pathway might be associated with the decidual cytokine regulation. Upregulation of miR-146a inhibited the expression of the predicted molecules enriched in the TLR pathway and improved the cytokine disorder in unexplained SA deciduae-derived DICs. Collectively, miR-146a improves the decidual cytokine microenvironment by regulating the TLR pathway in unexplained SA, providing novel potential targets for further therapeutic research.

12.
J Food Sci ; 85(11): 3998-4008, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33001454

RESUMO

The mechanism underlying the effect of ursolic acid (UA) on lipid metabolism remains unclear. This study aimed to explore the mechanisms of UA in reducing lipid accumulation in free fatty acids-cultured HepG2 cells and in high-fat-diet-fed C57BL/6J mice. In vivo, UA effectively alleviated liver steatosis and decreased the size of adipocytes in the epididymis. It also significantly decreased the total cholesterol (TC) and triglyceride (TG) contents in the liver and plasma in C57BL/6 mice. In vitro, UA (20 µM) significantly reduced lipid accumulation; the intracellular TC contents decreased from 0.078 ± 0.0047 to 0.049 ± 0.0064 µmol/mg protein, and TG contents from 0.133 ± 0.005 to 0.066 ± 0.0047 µmol/mg protein, in HepG2 cells. Furthermore, UA reduced the mRNA expression related to fat synthesis, enhanced the mRNA expression related to adipose decomposition, and dramatically upregulated the protein expression of P-AMPK in vivo and in vitro. Of note, these protective effects of UA on a high-fat environment were blocked by the AMPK inhibitor (compound C) in vitro. In addition, the molecular docking results suggested that UA could be docked to the AMPK protein as an AMPK activator. These results indicated that UA lowered the lipid content probably via activating the AMPK signaling pathway, thereby inhibiting lipid synthesis and promoting fat decomposition. PRACTICAL APPLICATION: Ursolic acid (UA) widely exists in vegetables and fruits. This study highlighted a lipid-lowing mechanism of UA in HepG2 cells and C57BL/6J mice. The data indicated that UA might be used in lipid-lowering functional foods.

13.
BMC Med Inform Decis Mak ; 20(1): 239, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32957985

RESUMO

BACKGROUND: The present study aims to investigate the role of histogram analysis of intravoxel incoherent motion (IVIM) in the differential diagnosis of benign and malignant breast lesions. METHODS: The magnetic resonance imaging and clinical data of 55 patients (63 lesions) were retrospectively analyzed. The multi-b-valued diffusion-weighted imaging image was processed using the MADC software to obtain the gray-scaled maps of apparent diffusion coefficient (ADC)-slow, ADC-fast and f. The MaZda software was used to extract the histogram metrics of these maps. Combined with the conventional sequence images, the region of interest (ROI) was manually drawn along the edge of the lesion at the maximum level of the gray-scale image, and the difference of the data was analyzed between the benign and malignant breast lesions. RESULTS: There were 29 patients with 37 benign lesions, which included 23 fibroadenomas, 6 adenosis, 1 breast cysts, 4 intraductal papillomas, and 3 inflammations of breast. Furthermore, 26 malignant lesions in 26 patients, which included 20 non-specific invasive ductal carcinomas, 5 intraductal carcinomas and 1 patient with squamous cell carcinoma. The ADC-slow (mean and the 50th percentile) and f (minimum, mean, kurtosis, the 10th percentile and 50th percentile) of these malignant breast lesions were significantly lower than those of benign lesions (P < 0.05), while ADC-fast (kurtosis) and f (variance, skewness) of these malignant breast lesions were significantly higher than those of benign lesions (P < 0.05). CONCLUSION: The histogram analysis of ADC-slow (mean and the 50th percentile), ADC-fast (kurtosis) and f (minimum, mean, kurtosis, the 10th percentile and 50th percentile. Variance, skewness) can provide a more objective and accurate basis for the differential diagnosis of benign and malignant breast lesions.

14.
Biometrics ; 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32909618

RESUMO

The outcome in a randomized experiment is sometimes nonnegative with a clump of observations at zero and continuously distributed positive values. One widely used model for a nonnegative outcome with a clump at zero is the Tobit model, which assumes that the treatment has a shift effect on the distribution of a normally distributed latent variable and the observed outcome is the maximum of the latent variable and zero. We develop a class of semiparametric models and inference procedures that extend the Tobit model in two useful directions. First, we consider more flexible models for the treatment effect than the shift effect of the Tobit model; for example, our models allow for the treatment to have a larger in magnitude effect for upper quantiles. Second, we make semiparametric inferences using empirical likelihood that allow the underlying latent variable to have any distribution, unlike the original Tobit model that assumes the latent variable is normally distributed. We apply our approach to data from the RAND Health Insurance Experiment. We also extend our approach to observational studies in which treatment assignment is strongly ignorable.

15.
Curr Med Res Opin ; 36(11): 1807-1812, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32936052

RESUMO

OBJECTIVE: Acute myeloid leukemia (AML) is a hematopoietic stem cell malignancy and the most common type of leukemia, with the 5-year relative survival rate of 19% in Europe. Chronic myeloid leukemia (CML) is a slowly progressive clonal malignant disease, and a myeloproliferative disorder which is derived from biphasic hematopoietic stem cells but driven by progenitor cells. AML following CML is common, which can be caused by an antecedent myeloid malignancy, leukemogenic therapy, or without an identifiable prodrome or exposure to cytotoxic agents. However, the case of secondary chronic myeloid leukemia following acute myeloid leukemia treated with autologous hematopoietic stem cell transplantation is rare. METHODS: Here we report a unique case of secondary CML after AML treated by chemotherapy and autologous peripheral blood stem cell transplantation. The 34-year-old male was diagnosed with AML subtype M5b according to clinical features in 2011. The patient was treated with the MAE program (mitoxantrone, cytosine arabinoside, etoposide) for two courses, followed by the IAE program (idarubicin, cytosine arabinoside, etoposide) and cytosine arabinoside for consolidation chemotherapy. An autologous hematopoietic stem cell transplantation with prophylactic intrathecal methotrexate cytarabine and dexamethasone was initiated. RESULTS: Subsequently, the patient achieved complete remission in 2012. After 4 years, the patient presented with leukocyte elevation of more than 4 months, and then was diagnosed with secondary CML. Based on this diagnosis, and with respect to the patient's severely compromised overall condition, tyrosine kinase inhibitors (TKI) therapy was conducted in 2016. The patient achieved, and continue to be in, complete remission. CONCLUSIONS: The case expands the understanding of secondary CML and emphasizes the importance of oncological vigilance in patients with secondary CML after AML therapy.

16.
J Cell Mol Med ; 24(20): 11718-11728, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32881246

RESUMO

Pioglitazone (PIO) attenuates cisplatin nephrotoxicity whereas the underlying mechanism remains unknown. Apoptosis is associated with mitochondrial dysfunction and SIRT1 activation can decrease cell apoptosis in cisplatin nephrotoxicity. Therefore, we explored whether the protective effect of PIO in cisplatin nephrotoxicity is achieved by suppressing mitochondria-mediated apoptosis through SIRT1/p53 signalling regulation. Cell viability, apoptosis, survival rate, renal pathology and function were examined. Moreover, we also analysed the expression of SIRT1, Acetyl-p53, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mitochondrial permeability transition pore (mPTP) opening, adenosine triphosphate (ATP) and apoptosis-related protein in vivo and in vitro. Pioglitazone treatment significantly increased cell viability, promoted SIRT1-p53 interaction, upregulated Bcl-2 expression, activated SIRT1 and elevated mitochondrial ATP synthesis after cisplatin treatment. However, PIO decreased the generation of ROS, opening of mPTP, dissipation of MMP and translocation of cytochrome c after cisplatin treatment. Pioglitazone also reduced the activation of caspase-3 and caspase-9, lowered the ratio of Bax/Bcl-2, attenuated kidney pathological damage and dysfunction, down-regulated the expression of Acetyl-p53, PUMA-α and Bax and abated cell apoptosis after cisplatin treatment. The SIRT1 inhibitor, EX527, clearly reversed the protective effects of PIO. These results implied PIO attenuated cisplatin nephrotoxicity by suppressing mitochondria-mediated apoptosis through regulating SIRT1/p53 signalling.

17.
Anal Chim Acta ; 1133: 1-10, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-32993861

RESUMO

Triphenyl phosphate (TPhP), a typical model of organophosphorus flame retardants (OPFRs), has been regarded as emerging environmental contaminants of health concern. In this study, TPhP molecularly imprinted polymers immobilized on graphene oxide (GO) film (TPhP-MIPs/GO) monolithic fiber for direct immersion solid phase microextraction (DI-SPME) was fabricated and evaluated. Compared with TPhP molecularly imprinted polymers (TPhP-MIPs) monolithic fiber, TPhP-MIPs/GO fiber had bigger extraction capacity, stronger hydrophilicity and faster mass transfer rate. Furthermore, TPhP-MIPs/GO fiber displayed excellent selectivity for TPhP among its structure analogues. It was thermally stable up to 320 °C so that it can withstand the high temperature of gas chromatography (GC) injection port for desorption and detection by flame photometric detector (FPD). Under optimal conditions, TPhP-MIPs/GO-SPME-GC/FPD method was developed by yielding satisfactory ultralow limit of quantification (0.4 ng L-1); linearity (≥0.99), good intra- and inter-day precision for a single fiber and fiber-to-fiber reproducibility. The method was applied for the determination of TPhP in environmental water and the relative recoveries were found to be in the range from 70 to 110%. TPhP was detected in three out of four environmental water samples at concentration levels from 0.04 to 0.12 ng mL-1, illustrating light pollution of TPhP in most environmental water.

18.
Biochim Biophys Acta Mol Basis Dis ; 1867(1): 165966, 2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32931889

RESUMO

BACKGROUND: Esophageal Squamous Cell Carcinoma (ESCC) is an aggressive malignancy, leading to more than 250,000 deaths in China every year. However, the pathogenesis of ESCC remains unclear, which hinders the diagnosis and treatment of the disease in clinic. METHOD: To elucidate underlying mechanism and identify potential biomarkers, an integrative strategy of combining transcriptome and metabolome has been implemented to find potential causal genes and metabolites for ESCC. RESULTS: At the transcriptional level, dysregulated genes in ESCC patients were identified and pathway enrichment analysis discovered tyrosine metabolic pathway as a promising target. Subsequently, up- and down-stream metabolites of tyrosine pathway were explored through targeted metabolome approach. Five metabolites, i.e. phenylalanine, 4-hydroxyphenyllactic acid, 3,4-dihydroxyphenylalanine, 3,4-dihydroxyphenylacetic acid and tyrosine were identified as diagnosis biomarkers for ESCC and metastatic ESCC patients. A biological model incorporating both transcriptional and metabolic dysregulation was also established to illustrate the potential mechanism of tumorigenesis and metastasis for ESCC. CONCLUSION: Integrative transcriptomics and metabolomics analysis suggested that tyrosine pathway was essential for the tumorigenesis and metastasis of ESCC primarily through altering immune response and regulating tumor microenvironment. This research sheds light on the pathogenesis of ESCC and discovers potential biomarkers for the diagnosis of the disease.

19.
Anesthesiology ; 133(6): 1244-1259, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32997750

RESUMO

BACKGROUND: Acid-sensing ion channel 3 (ASIC3) upregulation has been reported in dorsal root ganglion neurons after incision and contributes to postoperative nociception. This study hypothesized that upregulation of ASIC3 in incised tissues is induced by nerve growth factor through the phosphoinositide 3-kinase/protein kinase B signaling pathway. METHODS: A plantar incision model was established in adult male and female Sprague-Dawley rats. ASIC3 was inhibited by APETx2 treatment, small interfering RNA treatment, or ASIC3 knockout. Sciatic nerve ligation was performed to analyze ASIC3 transport. A nerve growth factor antibody and a phosphoinositide 3-kinase inhibitor were used to investigate the mechanism by which nerve growth factor regulates ASIC3 expression. RESULTS: Acid-sensing ion channel 3 inhibition decreased incisional guarding and mechanical nociception. ASIC3 protein levels were increased in skin and muscle 4 h after incision (mean ± SD: 5.4 ± 3.2-fold in skin, n = 6, P = 0.001; 4.3 ± 2.2-fold in muscle, n = 6, P = 0.001). Sciatic nerve ligation revealed bidirectional ASIC3 transport. Nerve growth factor antibody treatment inhibited the expression of ASIC3 (mean ± SD: antibody 2.3 ± 0.8-fold vs. vehicle 4.9 ± 2.4-fold, n = 6, P = 0.036) and phosphorylated protein kinase B (mean ± SD: antibody 0.8 ± 0.3-fold vs. vehicle 1.8 ± 0.8-fold, n = 6, P = 0.010) in incised tissues. Intraplantar injection of nerve growth factor increased the expression of ASIC3 and phosphorylated protein kinase B. ASIC3 expression and incisional pain-related behaviors were inhibited by pretreatment with the phosphoinositide 3-kinase inhibitor LY294002. CONCLUSIONS: Acid-sensing ion channel 3 overexpression in incisions contributes to postoperative guarding and mechanical nociception. Bidirectional transport of ASIC3 between incised tissues and dorsal root ganglion neurons occurs through the sciatic nerve. Nerve growth factor regulates ASIC3 expression after plantar incision through the phosphoinositide 3-kinase/protein kinase B signaling pathway.

20.
Chem Commun (Camb) ; 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32808622

RESUMO

A novel photo-responsive surface was constructed via modifying azobenzene-calix[4]arene (ABC4) on a microstructured silicon surface. Asymmetric UV light irradiation could drive the macroscopic directional motion of a water droplet on this photo-responsive surface.

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