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1.
Aging (Albany NY) ; 112019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31796646

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a relevant risk factor for developing hepatocellular carcinoma (HCC). Steatohepatitic HCC (SH-HCC), characterized by HCC with steatosis, is influenced by lipid metabolism disorders. A hypoxic microenvironment is common in HCC and affects lipid metabolism. However, whether hypoxia-induced HIF-2α upregulation exacerbates lipid accumulation to contribute to SH-HCC progression remains unclear. In this study, we demonstrated that HIF-2α was elevated in tissues from NAFLD-HCC patients and was associated with survival. Under hypoxic conditions, upregulated HIF-2α was accompanied by lipid accumulation and PI3K-AKT-mTOR pathway activation. HIF-2α knockdown (KD) in steatotic HCC ameliorated triglyceride accumulation and steatosis. HIF-2α-KD steatotic HCC showed minimal lipid synthesis in a hypoxic environment, which contributes to a reduction in malignant behaviours. However, treatment with MHY1485 restored these behaviours. STAM mice, a mouse model that develops NAFLD-HCC, exhibit more rapid tumour progression upon exposure to hypoxia. STAM mice treated with INK-128 presented abrogated mTOR expression and tumour progression under hypoxic conditions with lower triglycerides and steatosis. In conclusion, in a hypoxic microenvironment, HIF-2α upregulation promotes steatotic HCC progression by activating lipid synthesis via the PI3K-AKT-mTOR pathway. Therefore, HIF-2α can be a biomarker and target in developing specific therapeutic measures for NAFLD-HCC patients.

2.
J Proteome Res ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31789524

RESUMO

Advances in protein tagging and mass spectrometry (MS) have enabled generation of large quantitative proteome and phosphoproteome data sets, for identifying differentially expressed targets in case-control studies. Power study of statistical tests is critical for designing strategies for effective target identification and control of experimental cost. Here, we develop a simulation framework to generate realistic phospho-peptide data with known changes between cases and controls. Using this framework, we quantify the performance of traditional t-tests, Bayesian tests, and the ranking-by-fold-change test. Bayesian tests, which share variance information among peptides, outperform the traditional t-tests. Although ranking-by-fold-change has similar power as the Bayesian tests, its type I error rate cannot be properly controlled without proper permutation analysis; therefore, simply relying on the ranking likely brings false positives. Two-sample Bayesian tests considering dependencies between intensity and variance are superior for data sets with complex variance. While increasing the sample size enhances the statistical tests' performance, balanced controls and cases are recommended over a one-side weighted group. Further, higher peptide standard deviations require higher fold changes to achieve the same statistical power. Together, these results highlight the importance of model-informed experimental design and principled statistical analyses when working with large-scale proteomic and phosphoproteomic data.

3.
Plant Physiol Biochem ; 145: 95-106, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31675527

RESUMO

In order to improve the understanding of plant water relations under drought stress, the water use behavior of two Fragaria x ananassa Duch. cultivars, contrasting in their drought stress phenotype, is identified. Under drought, stomatal closure is gradual in Figaro. Based on this, we associate Figaro with conservative water use behavior. Contrarily, drought stress causes a sudden and steep decrease in stomatal conductance in Flair, leading to the identification of Flair as a prodigal water use behavior cultivar. Responses to progressive drought on the one hand and an osmotic shock on the other hand are compared between these two cultivars. Tonoplast intrinsic protein mRNA levels are shown to be upregulated under progressive drought in the roots of Figaro only. Otherwise, aquaporin expression upon drought or osmotic stress is similar between both cultivars, i.e. plasma membrane intrinsic proteins are downregulated under progressive drought in leaves and under short term osmotic shock in roots. In response to osmotic shock, root hydraulic conductivity did not change significantly and stomatal closure is equal in both cultivars. De novo abscisic acid biosynthesis is upregulated in the roots of both cultivars under progressive drought.

4.
Chin Med J (Engl) ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31764182

RESUMO

BACKGROUND: Artificial intelligence-assisted image recognition technology is currently able to detect the target area of an image and fetch information to make classifications according to target features. This study aimed to use deep neural networks for computed tomography (CT) diagnosis of perigastric metastatic lymph nodes (PGMLNs) to simulate the recognition of lymph nodes by radiologists, and to acquire more accurate identification results. METHODS: A total of 1371 images of suspected lymph node metastasis from enhanced abdominal CT scans were identified and labeled by radiologists and were used with 18,780 original images for faster region-based convolutional neural networks (FR-CNN) deep learning. The identification results of 6000 random CT images from 100 gastric cancer patients by the FR-CNN were compared with results obtained from radiologists in terms of their identification accuracy. Similarly, 1004 CT images with metastatic lymph nodes that had been post-operatively confirmed by pathological examination and 11,340 original images were used in the identification and learning processes described above. The same 6000 gastric cancer CT images were used for the verification, according to which the diagnosis results were analyzed. RESULTS: In the initial group, precision-recall curves were generated based on the precision rates, the recall rates of nodule classes of the training set and the validation set; the mean average precision (mAP) value was 0.5019. To verify the results of the initial learning group, the receiver operating characteristic curves was generated, and the corresponding area under the curve (AUC) value was calculated as 0.8995. After the second phase of precise learning, all the indicators were improved, and the mAP and AUC values were 0.7801 and 0.9541, respectively. CONCLUSION: Through deep learning, FR-CNN achieved high judgment effectiveness and recognition accuracy for CT diagnosis of PGMLNs. TRIAL REGISTRATION: Chinese Clinical Trial Registry, No. ChiCTR1800016787; http://www.chictr.org.cn/showproj.aspx?proj=28515.

5.
Hum Cell ; 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31758392

RESUMO

MiR-663b has been demonstrated to be abnormally expressed in several cancer types and was involved in the progression of cancer. Although overexpression of miR-663b in colorectal cancer was observed, the role of miR-663b in colorectal cancer cells has not been identified yet. In this study, we analyzed expression of miR-663b in colorectal tumors and explored the molecular mechanism of miR-663b in colorectal cancer cells. MiR-663b was significantly overexpressed in colorectal tumors and cell lines. Downregulation of miR-663b inhibited cell proliferation and sphere forming ability in colorectal cancer cells. In addition, miR-663b downregulation inactivated Ras/Raf signaling activity and subsequently decreased YAP1 and CD44 expression in colorectal cancer cells. Using TargetScan software, TNK1, a negative regulator of Ras/Raf signaling, was predicted to be a target gene of miR-663b. Western blotting and RT-qPCR showed that TNK1 expression was negatively regulated by miR-663b. In addition, the direct binding of miR-663b to TNK1 mRNA was proved by dual luciferase reporter assay. Furthermore, downregulation of miR-663b inhibited colorectal cancer cell proliferation and stemness, which was reversed after siRNA-mediated silencing of TNK1. In conclusion, the current study revealed a pivotal role of miR-663b in the progression of colorectal cancer.

6.
Epilepsy Behav ; 101(Pt A): 106519, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31706168

RESUMO

OBJECTIVE: The objective of the study was to localize sources of interictal high-frequency activity (HFA), from tripolar electroencephalography (tEEG), in patient-specific, realistic head models. METHODS: Concurrent electroencephalogram (EEG) and tEEG were recorded from nine patients undergoing video-EEG, of which eight had seizures during the recordings and the other had epileptic activity. Patient-specific, realistic boundary element head models were generated from the patient's magnetic resonance images (MRIs). Forward and inverse modeling was performed to localize the HFA to cortical surfaces. RESULTS: In the present study, performed on nine patients with epilepsy, HFA observed in the tEEG was localized to the surface of subject-specific, realistic, cortical models, and found to occur almost exclusively in the seizure onset zone (SOZ)/irritative zone (IZ). SIGNIFICANCE: High-frequency oscillations (HFOs) have been studied as precise biomarkers of the SOZ in epilepsy and have resulted in good therapeutic effect in surgical candidates. Knowing where the sources of these highly focal events are located in the brain can help with diagnosis. High-frequency oscillations are not commonly observed in noninvasive EEG recordings, and invasive electrocorticography (ECoG) is usually required to detect them. However, tEEG, i.e., EEG recorded on the scalp with tripolar concentric ring electrodes (TCREs), has been found to detect narrowband HFA from high gamma (approximately 80 Hz) to almost 400 Hz that correlates with SOZ diagnosis. Thus, source localization of HFA in tEEG may help clinicians identify brain regions of the epileptic zone. At the least, the tEEG HFA localization may help determine where to perform intracranial recordings used for precise diagnosis.

7.
Knee ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31727431

RESUMO

BACKGROUND: Stromal cell-derived factor-1a (SDF-1α) and high mobility group box chromosomal protein 1 (HMGB1) are chemokines that can drive post-traumatic osteoarthritis (PTOA) induced by anterior cruciate ligament (ACL) injury. However, the influence of patient characteristics on expression of those chemokines remains unclear. Our aim was to determine the relationship between chemokine expression in synovial fluid (SF) of the ACL-deficient (ACL-D) knee and patient characteristics including time from injury, sex, and age. METHODS: SF samples were collected immediately prior to the first-time ACL reconstruction (ACLR) from 82 patients. Expression of SDF-1α and HMGB1 was measured with human-specific solid phase sandwich enzyme-linked immunosorbent assays. The expression levels between groups divided by time from injury, or age, or sex was compared using Student's t-test. The association of SDF-1α or HMGB1 levels with those variables was determined using regression analysis and Pearson product-moment correlation coefficient. RESULTS: Regression and correlation analysis indicated significant correlation between SDF-1α expression and time from injury in the cohort (r = -0.266, P = 0.016, n = 82) and in females (r = -0.386, P = 0.024, n = 34). Significant correlation was also observed between SDF-1α expression and age in the cohort (r = -0.224, P = 0.043, n = 82) and in males (r = -0.289, P = 0.046, n = 48). No significant correlation between HMGB1 expression and patient characteristics was detected. CONCLUSIONS: SDF-1α rather than HMGB1 might serve as a protein marker for monitoring the development of PTOA in the ACL-D knee, especially in female patients.

8.
Pathol Oncol Res ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31748880

RESUMO

Immune checkpoint blockade has demonstrated significant anti-tumor immunity in an array of cancer types, yet the underlying regulatory mechanism of it is still obscure, and many problems remain to be solved. As an inhibitory costimulatory signal of T-cells, the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway can paralyze T-cells at the tumor site, enabling the immune escape of tumor cells. Although many antibodies targeting PD-1/PD-L1 have been developed to block their interaction for the treatment of cancer, the reduced response rate and resistance to the therapies call for further comprehension of this pathway in the tumor microenvironment. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are two main types of noncoding RNAs that play critical parts in the regulation of immune response in tumorigenesis, including the PD-1/PD-L1 pathway. Here we summarize the most recent studies on the control of this pathway by noncoding RNAs in cancer and hopefully will offer new insights into immune checkpoint blockade therapies.

9.
Cells ; 8(12)2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31766744

RESUMO

Triple-negative breast cancer (TNBC) is the most aggressive, prevalent, and distinct subtype of breast cancer characterized by high recurrence rates and poor clinical prognosis, devoid of both predictive markers and potential therapeutic targets. MicroRNAs (miRNA/miR) are a family of small, endogenous, non-coding, single-stranded regulatory RNAs that bind to the 3'-untranslated region (3'-UTR) complementary sequences and downregulate the translation of target mRNAs as post-transcriptional regulators. Dysregulation miRNAs are involved in broad spectrum cellular processes of TNBC, exerting their function as oncogenes or tumor suppressors depending on their cellular target involved in tumor initiation, promotion, malignant conversion, and metastasis. In this review, we emphasize on masses of miRNAs that act as oncogenes or tumor suppressors involved in epithelial-mesenchymal transition (EMT), maintenance of stemness, tumor invasion and metastasis, cell proliferation, and apoptosis. We also discuss miRNAs as the targets or as the regulators of dysregulation epigenetic modulation in the carcinogenesis process of TNBC. Furthermore, we show that miRNAs used as potential classification, prognostic, chemotherapy and radiotherapy resistance markers in TNBC. Finally, we present the perspective on miRNA therapeutics with mimics or antagonists, and focus on the challenges of miRNA therapy. This study offers an insight into the role of miRNA in pathology progression of TNBC.

10.
FEBS Open Bio ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31769193

RESUMO

Colorectal cancer (CRC) remains a major cause of carcinoma-related deaths worldwide. MicroRNA-498 (miR-498) modulates the development of a variety of biological events, including tumorigenesis. Nevertheless, it is unclear whether miR-498 plays a role in CRC. This study was designed to elucidate the underlying mechanism and role of miR-498 in modulation of the viability and invasiveness of CRC cells. We report that CRC tissues and cells exhibited decreased expression of miR-498, and that overexpression of miR-498 resulted in reduced proliferation of CRC cells, concomitant with increased apoptosis. Furthermore, bioinformatic prediction and dual-luciferase reporter assay revealed that miR-498 targeted the 3'-UTR of Bcl-2 for silencing. However, Bcl-2 overexpression suppressed the pro-apoptotic of miR-498 on CRC cells. In summary, we describe here a possible role of miR-498 in CRC, which may lead to the identification of new targets for treatment of this malignancy.

11.
Aging (Albany NY) ; 11(19): 8139-8155, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31584879

RESUMO

This study aims to explore the expression and degree of methylation of lncRNA MEG3 in gastric cancer tissues and to analyze its effect on the migration and proliferation of gastric cancer patients and the mechanism by which this occurs. The targeting relationship between MEG3, miR-181a-5p and ATP4B was detected through molecular biology experiments. Wound healing, transwell, colony formation and flow cytometry assays were used to analyze the effects of lncRNA MEG3 and methylation on tumor cell migration, invasion, proliferation and apoptosis. In addition, a tumor xenotransplantation model was established to study the influence of MEG3 on tumor growth in vivo. Bioinformatics analysis showed that lncRNA MEG3 and ATP4B were downregulated in gastric cancer tissues compared with normal tissues. Bioinformatics predicted that ATP4B might be regulated by targeting miR-181a-5p. The overexpression of MEG3 and the application of 5-Aza treatment inhibited the migration, invasion and proliferation of MGC-803 cells and promoted apoptosis. In gastric cancer tissues, MEG3 is hypermethylated to decrease expression. Once the expression of MEG3 is restored or methylation is inhibited, tumor growth can be inhibited both in vivo and in vitro. This finding could be utilized as a clinical reference for gastric cancer treatment in the future.

12.
ACS Appl Mater Interfaces ; 11(44): 41440-41447, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31615201

RESUMO

The big challenging issues in photocatalytic H2 evolution are efficient separation of the photoinduced carriers, the stability of the catalyst, enhancing quantum efficiency, and requiring photoinduced electrons to enrich on photocatalysts' surface. Herein, Ti3C2 MXene quantum dots (QDs) possess the activity of Pt as a co-catalyst in promoting the photocatalytic H2 evolution to form heterostructures with g-C3N4 nanosheets (NSs) (denoted g-C3N4@Ti3C2 QDs). The photocatalytic H2 evolution rate of g-C3N4@Ti3C2 QD composites with an optimized Ti3C2 QD loading amounts (100 mL) is nearly 26, 3 and 10 times higher than pristine g-C3N4 NSs, Pt/g-C3N4, and Ti3C2 MXene sheet/g-C3N4, respectively. The Ti3C2 QDs increase the specific surface area of g-C3N4 and boost the density of the active site. Besides, metallic Ti3C2 QDs possess excellent electronic conductivity, causing the improvement of carrier transfer efficiency.

13.
Water Sci Technol ; 80(4): 620-633, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31661441

RESUMO

The treatment of toxic and difficult-to-degrade phenolic compounds has become a key issue in the coking, pharmaceutical, and chemical industries. Considering the polymerization and oxidation of phenolic compounds in supercritical water partial oxidation/supercritical water oxidation (SCWPO/SCWO), the present study reviewed the removal efficiency and reaction pathway of phenolic compounds and phenolic waste/wastewater under different reaction conditions. Temperature is the dominant factor affecting the SCWO reaction. When the oxidizing ability is insufficient, the organics polymerize to form phenolic compounds. The gradual increase of oxidant equivalent causes the intermediate product to gradually oxidize to CO2 and H2O completely. Finally, the free radical reaction mechanism is considered to be a typical SCWO reaction mechanism.


Assuntos
Purificação da Água , Água , Oxirredução , Fenóis , Polimerização
14.
J Adv Nurs ; 75(12): 3424-3433, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31524296

RESUMO

AIMS: To evaluate the application effect of individualized pressure setting strategy of pneumatic tourniquet in orthopaedic surgery. BACKGROUND: Some individualized setting pressures of pneumatic tourniquet are lower than the standard pressure recommended in the textbook (Nursing of Operating Room, People's Military Publishing House, 2008). DESIGN: Meta-analysis. DATA SOURCES: CL, WOS, PubMed, CNKI, CBM, VIP and Wan-fang DATA. REVIEW METHODS: We searched studies on the application effect of individualized pressure of pneumatic tourniquet from the establishment date of the databases to September 2017. Study quality was assessed using the quality evaluation method recommended in the Cochrane Handbook 5.1.0 (Higgins, 2011). The primary outcome was inflation pressure. RESULTS: We identified nine studies including 1,200 patients. The individualized pressure setting strategy can provide a lower inflation pressure (four studies), improve haemostatic effect (six studies) and reduce the incidence of related complications (eight studies). CONCLUSIONS: An individualized inflation pressure is recommended when using the tourniquet in orthopaedic surgery. And the setting pressure might be a minimum and efficiency one, by accessing the the systolic blood pressure and limb circumferences of the patient. IMPACT: This study addressed that the individualized pressure setting strategy of pneumatic tourniquet can provide a lower inflation pressure and a higher application value in orthopaedic limb surgery. However, greater attention should be focused on how to unify the individualized pressure setting strategy. Meanwhile, the instructions for use from manufacturers need to be updated. Therefore, it is recommended to conduct a large-sample multi-centre high-quality randomized controlled trial in strict accordance with the CONSORT standard.

15.
J Transl Med ; 17(1): 256, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391086

RESUMO

BACKGROUND: The adipose afferent reflex (AAR), a sympatho-excitatory reflex, can promote the elevation of sympathetic nerve activity (SNA) and blood pressure (BP). Inflammation in the paraventricular nucleus (PVN) involves sympathetic abnormality in some cardiovascular diseases such as hypertension. This study was designed to explore the effects of tumor necrosis factor alpha (TNFα) in the PVN on the AAR and SNA in rats with obesity-related hypertension (OH) induced by a high-fat diet for 12 weeks. METHODS: Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were continuously recorded in anesthetized rats, and their responses to capsaicin (CAP) stimulation of the right inguinal white adipose tissue were used to evaluate the AAR. RESULTS: Compared to the control rats, the systolic blood pressure (SBP), plasma norepinephrine (NE, indicating SNA) and TNFα levels, TNFα mRNA and protein levels, reactive oxygen species (ROS) content and NADPH oxidase activity in the PVN were significantly elevated in rats with OH. TNFα in the PVN markedly enhanced sympathoexcitation and AAR. Moreover, the enhancement of AAR caused by TNFα can be significantly strengthened by the pretreatment of diethyldithiocarbamate (DETC), a superoxide dismutase inhibitor, but attenuated by TNF-α receptor antagonist R-7050, superoxide scavenger PEG-SOD and NADPH oxidase inhibitor apocynin (Apo) in rats with OH. Acute microinjection of TNF-α into the PVN significantly increased the activity of NADPH oxidase and ROS levels in rats with OH, which were effectively blocked by R-7050. Furthermore, our results also showed that the increased levels of ROS, TNFα and NADPH oxidase subunits mRNA and protein in the PVN of rats with OH were significantly reversed by pentoxifylline (PTX, 30 mg/kg daily ip; in 10% ethanol) application, a cytokine blocker, for a period of 5 weeks. PTX administration also significantly decreased SBP, AAR and plasma NE levels in rats with OH. CONCLUSIONS: TNFα in the PVN modulates AAR and contributes to sympathoexcitation in OH possibly through NADPH oxidase-dependent ROS generation. TNFα blockade attenuates AAR and sympathoexcitation that unveils TNFα in the PVN may be a possible therapeutic target for the intervention of OH.

16.
Eur J Radiol ; 118: 194-199, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31439242

RESUMO

PURPOSE: To explore the role of intratumoral heterogeneity on MRI assessed by histogram analysis in differentiating soft-tissue sarcomas (STS) of different grades. MATERIALS AND METHODS: Patients with primary STS undergoing MRI prior to iatrogenic procedures were included retrospectively. The histologic grade was assigned according to Federation Nationale des Centres de Lutte Contre le Cancer grading system. T1WI and T2WI were normalized by dividing mean signal intensity (SI) of contralateral/near unaffected muscles. Contrast-enhanced T1WI was normalized by computing enhancement ratio (ER) map as (SIpost-SIpre)/SIpre×100, where SIpre and SIpost represent SI of each pixel before and after enhancement. A region of interest (ROI) was manually drawn to include entire tumor area on axial slice with largest tumor diameter. Mean, mode, standard deviation, kurtosis and skewness on ROIs were extracted with ImageJ software. ANOVA/Kruskal-Wallis test was used to determine the significance of differences. ROC curve was applied for statistically significant parameters. P value ≤0.05 was considered statistically significant. RESULTS: Among involved 67 patients, 8 were assigned to grade 1, 38 to grade 2 and 21 to grade 3. Skewness (P =  0.022) and kurtosis (P =  0.035) on ER maps were significantly different among STS of different grades. The optimal cutoffs of skewness and kurtosis on ER maps were -0.488 (AUC[95% CI] 0.747[0.557-0.937]; sensitivity/specificity, 62.5%/86.4%) and 0.762 (AUC[95% CI] 0.684[0.548-0.821]; sensitivity/specificity, 76.2%/56.5%), respectively. CONCLUSION: Intratumoral heterogeneity on MRI quantitatively displayed by histogram parameters can differentiate STS of different grades. Skewness and kurtosis on ER maps show the capacity.

17.
Top Stroke Rehabil ; 26(8): 621-629, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31369355

RESUMO

Background: Transitional care (TC) has been shown to improve stroke rehabilitation in discharged stroke patients. Previous TC interventions did not report satisfactory stroke rehabilitation outcomes or risk management. Incorporating a health behavior theory in interventions can effectively improve health behaviors and metabolic indicators.Objectives: This study was a clinical controlled trial to investigate the impact of the Integrated Behavioral Model (IBM)-based 3-month TC on health behaviors, clinical outcomes, and stroke knowledge in discharged elderly stroke patients.Methods: Sixty elderly patients were recruited from two wards of a public teaching hospital in China. To prevent potential treatment contamination, patients were allocated into either a control or intervention group depending on which wards they were admitted to. The TC intervention considered all the IBM constructs to provide patients assistance in implementing health behaviors as recommended by the Chinese stroke guidelines. The TC intervention commenced one day before discharge and lasted three months after discharge. A linear mixed model was used to measure the impact of the intervention.Results: The TC intervention improved the discharged elderly stroke patients' health behaviors, activities of daily living, quality of life, and stroke knowledge. The intervention also controlled the patients' systolic blood pressure, body mass index, total cholesterol, triglycerides, and low-density lipoprotein cholesterol.Conclusions: This study provided evidence of concurrent self-reported and objective clinical indicators in discharged elderly stroke patients for the impact of the IBM-based 3-month TC intervention, which can be recommended for clinical practice.

18.
Int J Mol Sci ; 20(17)2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31461977

RESUMO

Vascular calcification can be enhanced by hyperglycemia. Elastin loss in tunica media promotes the osteogenic transformation of smooth muscle cells (SMCs) and involves arterial medial calcification (AMC) that is associated with a high incidence of cardiovascular risk in patients with type 2 diabetes. Here, we tested whether hydrogen sulfide (H2S), an endogenous gaseous mediator, can prevent elastin loss and attenuate calcification induced by high glucose in SMCs. Calcification was induced by high glucose (4500 mg/L) in human aortic SMCs (HASMCs) under the condition of calcifying medium containing 10 mM ß-glycerophosphate (ß-GP). The experiments showed that NaHS (an H2S donor, 100 µM) mitigated the calcification of HASMCs treated with high glucose by decreasing calcium and phosphorus levels, calcium deposition and ALP activity and inhibited osteogenic transformation by increasing SMα-actin and SM22α, two phenotypic markers of smooth muscle cells, and decreasing core binding factor α-1 (Cbfα-1), a key factor in bone formation, protein expressions in HASMCs. Moreover, NaHS administration inhibited the activation of Stat3, cathepsin S (CAS) activity and its expression, but increased the level of elastin protein. Pharmacological inhibition or gene silencing Stat3 not only reversed elastin loss, but also attenuated CAS expression. Inhibition of CAS alleviated, while CAS overexpression exacerbated, elastin loss. Interestingly, overexpression of wild type (WT)-Stat3, but not its mutant C259S, elevated CAS protein expression and reduced elastin level. Moreover, NaHS induced S-sulfhydration in WT, but not in the C259S Stat3. These data suggest that H2S may directly regulate Cys259 residue in Stat3 and then impair its signaling function. Our data indicate that H2S may attenuate vascular calcification by upregulating elastin level through the inhibition of Stat3/CAS signaling.

19.
Int J Mol Sci ; 20(17)2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31466304

RESUMO

Increased reactive oxygen species (ROS) induced by angiotensin II (Ang II) in the paraventricular nucleus (PVN) play a critical role in sympathetic overdrive in hypertension (OH). Intermedin (IMD), a bioactive peptide, has extensive clinically prospects in preventing and treating cardiovascular diseases. The study was designed to test the hypothesis that IMD in the PVN can inhibit the generation of ROS caused by Ang II for attenuating sympathetic nerve activity (SNA) and blood pressure (BP) in rats with obesity-related hypertension (OH). Male Sprague-Dawley rats (160-180 g) were used to induce OH by feeding of a high-fat diet (42% kcal as fat) for 12 weeks. The dynamic changes of sympathetic outflow were evaluated as the alterations of renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses to certain chemicals. The results showed that the protein expressions of Ang II type 1 receptor (AT1R), calcitonin receptor-like receptor (CRLR) and receptor activity-modifying protein 2 (RAMP2) and RAMP3 were markedly increased, but IMD was much lower in OH rats when compared to control rats. IMD itself microinjection into PVN not only lowered SNA, NADPH oxidase activity and ROS level, but also decreased Ang II-caused sympathetic overdrive, and increased NADPH oxidase activity, ROS levels and mitogen-activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) activation in OH rats. However, those effects were mostly blocked by the adrenomedullin (AM) receptor antagonist AM22-52 pretreatment. The enhancement of SNA caused by Ang II can be significantly attenuated by the pretreatment of AT1R antagonist lorsatan, superoxide scavenger Tempol and NADPH oxidase inhibitor apocynin (Apo) in OH rats. ERK activation inhibitor U0126 in the PVN reversed Ang II-induced enhancement of SNA, and Apo and IMD pretreatment in the PVN decreased Ang II-induced ERK activation. Chronic IMD administration in the PVN resulted in significant reductions in basal SNA and BP in OH rats. Moreover, IMD lowered NADPH oxidase activity and ROS level in the PVN; reduced the protein expressions of AT1R and NADPH oxidase subunits NOX2 and NOX4, and ERK activation in the PVN; and decreased Ang II levels-inducing sympathetic overactivation. These results indicated that IMD via AM receptors in the PVN attenuates SNA and hypertension, and decreases Ang II-induced enhancement of SNA through the inhibition of NADPH oxidase activity and ERK activation.

20.
Water Res ; 165: 114975, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31430653

RESUMO

Electrolysis and permanganate (PM) oxidation are two commonly used technologies for water treatment. However, they are often handicapped by their slow reaction rates. To improve the removal efficiency of refractory contaminants, we combined electrolysis with PM using an activated carbon fiber (ACF) as cathode (E-ACF-PM) for the first time to treat diclofenac (DCF) in aqueous solution. Up to 90% DCF was removed in 5 min by E-ACF-PM process. In comparison, only 3.95 and 27.35% of DCF was removed by individual electrolysis and PM oxidation at the same time, respectively. Acidic condition was more conducive to DCF removal. Surprisingly, soluble Mn(III) (aq) formed on the surface of ACF was demonstrated as the principal oxidizing agent in E-ACF-PM process. Further studies showed that all three components (electrolysis + ACF + PM) were necessary to facilitate the heterogeneous generation of reactive Mn(III) (aq). Moreover, SEM images and XPS spectra of ACF before and after treatment revealed that the morphologies and elemental compositions of reacted ACF were nearly unchanged during the E-ACF-PM process. ACF can be remained active and utilized to the rapid degradation of DCF in E-ACF-PM process even after reused for 20 times. Therefore, the E-ACF-PM process may provide a novel and effective alternative on the generation of reactive Mn(III) (aq) in situ for water treatment by green electrochemical reactions.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Fibra de Carbono , Diclofenaco , Compostos de Manganês , Oxirredução , Óxidos
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