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1.
Artigo em Inglês | MEDLINE | ID: mdl-32693572

RESUMO

A method capable of real-time and label-free monitoring of biomolecular interactions within whole blood, with-out any sample separation and label process is described. This was accomplished using silica colloidal crystal (SCC) films, three-dimensionally ordered silica particle arrays whose interference effect is a function of their optical thickness, as interfer-ence sensitive substrates. Interaction between immunoglobulins G (IgG) and protein A from staphylococcus aureus (SPA) con-jugates with changes in optical thickness of SCC films was monitored spectroscopically. Successful detection of IgG was achieved in buffer and whole blood. This system constitutes a simple label-free analysis showing great potential in monitoring interactions between biomolecules in complex biological media.

2.
J Exp Clin Cancer Res ; 39(1): 137, 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32677981

RESUMO

BACKGROUND: Hypoxia, a fundamental characteristic of glioma, is considered to promote tumor malignancy by inducing process of epithelial mesenchymal transition (EMT). Ferritin Light Chain (FTL) is one of the iron metabolism regulators and is overexpressed in glioma. However, relationship between hypoxia and FTL expression and its role in regulating EMT remains unclear. METHODS: Immunohistochemistry (IHC), western blot and public datasets were used to evaluate FTL level in glioma. Wound healing, transwell assays, CCK8, annexin V staining assay were used to measure migration, invasion, proliferation and apoptosis of glioma cells in vitro. Interaction between HIF1A and FTL was assessed by luciferase reporter and Chromatin immunoprecipitation (ChIP) assays. Subcutaneous xenograft model was established to investigate in vivo growth. RESULTS: FTL expression was enriched in high grade glioma (HGG) and its expression significantly associated with IDH1/2 wildtype and unfavorable prognosis of glioma patients. FTL expression positively correlated with HIF1A in glioma tissues and obviously increased in U87 and U251 cells under hypoxia in a time-dependent manner. Mechanistically, HIF-1α regulates FTL expression by directly binding to HRE-3 in FTL promoter region. Furthermore, we found that knockdown FTL dramatically repressed EMT and reduced migration and invasion of glioma by regulating AKT/GSK3ß/ ß-catenin signaling both in vitro and in vivo. Moreover, our study found downregulation FTL decreased the survival rate and increased the apoptosis of glioma cells treated with temozolomide (TMZ). FTL expression segregated glioma patients who were treated with TMZ or with high MGMT promoter methylation into survival groups in TCGA dataset. Patients with methylated MGMT who had high FTL expression presented similar prognosis with patients with unmethylated MGMT. CONCLUSION: Our study strongly suggested that hypoxia-inducible FTL was a regulator of EMT and acted not only as a prognostic marker but also a novel biomarker of response to TMZ in glioma.

3.
Opt Lett ; 45(14): 4072-4075, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32667357

RESUMO

In this work, we reported the design and fabrication of a compact and scalable metamaterial longpass filter with an ultrasmall footprint of 5.1µm×5.1µm. In the stopband, light transmission can be blocked and reflected with ∼25dB attenuation. In the passband, light can pass through with a low insertion loss around -0.28dB. The transition band can be redshifted or blueshifted by scaling up or down the filter block; i.e., scaling down 1% can produce a transition band blueshift of 11.4 nm. The power roll-off can be enhanced by cascading multiple filter blocks, i.e., 1.34 dB/nm by cascading three filters. These results demonstrate the great potential of the metamaterial-based waveguide devices for scalable photonic filtering applications.

4.
Minerva Cardioangiol ; 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32643894

RESUMO

BACKGROUND: Admission blood pressure was closely associated with adverse cardiac events in acute coronary syndrome (ACS) patients. However, data regarding comparison of resting postoperative systolic, diastolic, and mean blood pressure and pulse pressure with short- and long-term mortality in patients with acute coronary syndrome undergoing primary percutaneous coronary intervention (PCI) was still lacking. METHODS: 1,987 ACS patients undergoing primary PCI were analyzed, between January 2014 and October 2018. The primary outcomes were in-hospital cardiac and long-term all-cause mortality. RESULTS: Bar tendency chart and adjusted odds ratios showed that the resting postoperative SBP≤100mmHg, PP≤30mmHg and MAP≤70mmHg have higher in hospital cardiac (SBP: adjusted OR=9.42, 95%CI 1.95-45.53, p<0.01; PP: adjusted OR=8.61, 95%CI 2.53-29.30, p<0.01; MAP: adjusted OR=4.01, 95%CI 1.61-9.98, p<0.01) and long-term all-cause mortality (SBP: adjusted HR=4.18, 95%CI 1.43- 12.23, p<0.01; PP: adjusted HR=3.71, 95%CI 1.66-8.24, p<0.01; MAP: adjusted HR=2.54, 95%CI 1.14-5.65, p<0.01) , and the relationship between resting postoperative SBP and in-hospital cardiac or long-term all-cause mortality seemed to follow a J-shaped curve with increased event rates at low and high groups. CONCLUSIONS: The resting postoperative SBP≤100mmHg, PP≤30mmHg and MAP≤70mmHg are independent adverse prognosticators in ACS patients undergoing primary PCI, and the relationship between SBP and mortality looks like a J-shaped curve.

5.
Peptides ; 130: 170334, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32504765

RESUMO

The development of novel antifungal agents with high efficacy, low drug tolerance and few side effects is urgent. MSI-1 (GIWKFLKKAKKFWK-NH2), a cationic antimicrobial peptide, may be an attractive antifungal agent because of its structural characteristics, perfect stability against pH and high-temperature/salt, low toxicity towards mammalian cells and low potential for emergence of drug tolerance. In this study, the antifungal activity of MSI-1 in vitro and in a murine model of cryptococcal meningoencephalitis was evaluated. Zeta potential assay, flow cytometry, fluorescence microscope, transmission electron microscopy and microscale thermophoresis were performed to clarify the mechanisms underlying MSI-1 against C. neoformans. The results showed that MSI-1 exerted effective anti-cryptococcal activity in vitro, with MICs of 8-16 µg/mL and MFCs of 8-32 µg/mL, and in a C neoformans-infected mouse model, with significantly improved animal survival, decreased production of pro-inflammatory cytokines and alleviated lung injury, because the potent and rapid fungicidal activity of MSI-1 could effectively eliminate fungal counts in mouse organs. We confirmed that the positively charged peptide bound to C. neoformans by electrostatic attraction after interacting with glucuronoxylomannan (the primary component of C. neoformans capsule). Subsequently, MSI-1 increased the membrane fluidity of fungal cells and the cell membrane permeability, causing destabilized membrane integrity and leading to the final death of fungi. Collectively, MSI-1 possessed potent anti-cryptococcal activity via its notable membrane disruption effect and may be a potential candidate for use in antifungal infection induced by C. neoformans, especially azole-resistant cryptococcus.

6.
Chem Rev ; 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32543866

RESUMO

Transition-metal-catalyzed decarbonylation via carbon-carbon bond cleavage is an essential synthetic methodology. Given the ubiquity of carbonyl compounds, the selective decarbonylative process offers a distinct synthetic strategy using carbonyl groups as "traceless handles". This reaction has been significantly developed in recent years in many respects, including catalytic system development, mechanistic understanding, substrate scope, and application in the synthesis of complex functional molecules. Therefore, this review aims to summarize the recent progress on transition-metal-catalyzed decarbonylative process, from the discovery of new transformations to the understanding of reaction mechanisms, to reveal the great achievements and potentials in this field. The contents of this review are categorized by the type of chemical bond cleavage in the decarbonylative process. The main challenges and opportunities of the decarbonylative process are also examined with the goal of expanding the application range of decarbonylation reactions.

7.
Bioorg Med Chem ; 28(13): 115554, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32546299

RESUMO

Prostate cancer is the most common carcinoma of the male urinary system in developed countries. Androgen deprivation therapy has been commonly used in the treatment of prostate cancer for decades, but most patients will inevitably develop into more aggressive castration-resistant prostate cancer. Therefore, novel strategies are urgent to address this resistance mechanism. In this review, we discussed some new strategies for targeting androgen receptors through degradation pathways as potential treatments for prostate cancer.

8.
Neuroimage ; 218: 116957, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32442639

RESUMO

Anxious individuals tend to make pessimistic judgments in decision making under uncertainty. While this phenomenon is commonly attributed to risk aversion, loss aversion is a critical but often overlooked factor. In this study, we simultaneously examined risk aversion and loss aversion during decision making in high and low trait anxious individuals in a variable gain/loss gambling task during functional magnetic resonance imaging. Although high relative to low anxious individuals showed significant increased risk aversive behavior reflected by decreased overall gamble decisions, there was no group difference in subjective aversion to risk. Instead, loss aversion rather than risk aversion dominantly contributed to predict behavioral decisions, which was associated with attenuated functional connectivity between the amygdala-based emotional system and the prefrontal control regions. Our findings suggest a dominant role of loss aversion in maladaptive risk assessment of anxious individuals, underpinned by disorganization of emotion-related and cognitive-control-related brain networks.

9.
EBioMedicine ; 55: 102775, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32403086

RESUMO

BACKGROUND: The antibiotic resistance and biofilm formation of pathogenic microbes exacerbate the difficulties of anti-infection therapy in the clinic. The structural modification of antimicrobial peptides (AMP) is an effective strategy to develop novel anti-infective agents. METHOD: Seventeen amino acids (AA) in the longer chain of EeCentrocin 1 (from the edible sea-urchin Echinus esculentus) were truncated and underwent further modification. To produce lead peptides with low toxicity and high efficacy, the antimicrobial activity or cytotoxicity of peptides was evaluated against various multidrug-resistant bacteria/fungi or mammalian cells in vivo/ in vitro. In addition, the stability and modes of action of the lead peptide were investigated. FINDINGS: EC1-17KV displayed potent activity and an expanded antimicrobial spectrum, especially against drug-resistant gram-negative bacteria and fungi, attributable to its enhanced amphiphilicity and net charge. In addition, it exhibits bactericidal/fungicidal activity and effectively increased the animal survival rate and mitigated the histopathological damage induced by multidrug-resistant P. aeruginosa or C. albicans in infected mice or G. mellonella. Moreover, EC1-17KV had a poor ability to induce resistance in bacteria and fungi and exhibited desirable high-salt/high-temperature tolerance properties. In bacteria, EC1-17KV promoted divalent cation release to damage bacterial membrane integrity. In fungi, it changed C. albicans membrane fluidity to increase membrane permeabilization or reduced hyphal formation to suppress biofilm formation. INTERPRETATION: EC1-17KV is a promising lead peptide for the development of antimicrobial agents against antibiotic resistant bacteria and fungi. FUNDING: This work was funded by the National Natural Science Foundation of China (No. 81673483, 81803591); National Science and Technology Major Project Foundation of China (2019ZX09721001-004-005); National Key Research and Development Program of China (2018YFA0902000); "Double First-Class" University project (CPU2018GF/GY16); Natural Science Foundation of Jiangsu Province of China (No. BK20180563); and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

10.
Stroke ; 51(6): 1865-1867, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32390546

RESUMO

Background and Purpose- This study aimed to develop and validate a nomogram for predicting the risk of stroke recurrence among young adults after ischemic stroke. Methods- Patients aged between 18 and 49 years with first-ever ischemic stroke were selected from the Nanjing Stroke Registry Program. A stepwise Cox proportional hazards regression model was employed to develop the best-fit nomogram. The discrimination and calibration in the training and validation cohorts were used to evaluate the nomogram. All patients were classified into low-, intermediate-, and high-risk groups based on the risk scores generated from the nomogram. Results- A total of 604 patients were enrolled in this study. Hypertension (hazard ratio [HR], 2.038 [95% CI, 1.504-3.942]; P=0.034), diabetes mellitus (HR, 3.224 [95% CI, 1.848-5.624]; P<0.001), smoking status (current smokers versus nonsmokers; HR, 2.491 [95% CI, 1.304-4.759]; P=0.006), and stroke cause (small-vessel occlusion versus large-artery atherosclerosis; HR, 0.325 [95% CI, 0.109-0.976]; P=0.045) were associated with recurrent stroke. Educational years (>12 versus 0-6; HR, 0.070 [95% CI, 0.015-0.319]; P=0.001) were inversely correlated with recurrent stroke. The nomogram was composed of these factors, and successfully stratified patients into low-, intermediate-, and high-risk groups (P<0.001). Conclusions- The nomogram composed of hypertension, diabetes mellitus, smoking status, stroke cause, and education years may predict the risk of stroke recurrence among young adults after ischemic stroke.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32469704

RESUMO

BACKGROUND: Lung cancer is among the most common cancers worldwide, responsible for 13% of all new cancer cases. Also, is the leading cause of cancer death among both men and women. In this scenario, an effective and efficient treatment is required. OBJECTIVE: Production of two gold nanoparticles: 198Au and 99mTc-Au. The first one has been directed produced from irradiation of the 197Au in order to produce a beta-emitter gold nanoparticle for cancer therapy. The second one, has been directed produced from the radiolabeling of gold nanoparticles with technetium 99 metastable in order to produce imaging nanoagent. METHODS: The 198Au Nanoparticles were produced by irradiation and identified by hyper-purity germanium (HPGe). Then were evaluated in vitro in order to confirm the behavior on cell proliferation of lung cancer cell line, by the MTT methodology using A549 cells. The 99mTc-Au nanoparticles were produced by direct-radiolabeling with 99mTc and evaluated in vivo as intralesional nanoagent. RESULTS: The results showed that in both cases, all the nanoparticles have performed their duties with excellence. The 198Au nanoparticles were capable to kill lung cancer cells, while and 99mTc-Au was capable to image the tumor after intralesional injection. Also, 99mTc-Au nanoparticles were useful for biodistribution assay imaging, showing the main organs responsible for the nanoparticle uptake in healthy animals. CONCLUSION: The both gold nanoparticles showed to be a highly efficient nanoagent for both: therapy and diagnosing of lung cancer.

12.
J Stroke Cerebrovasc Dis ; 29(8): 104876, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32417236

RESUMO

BACKGROUND AND AIMS: Obstructive sleep apnea (OAS) is a common contributor as well as a frequent co-morbid condition in ischemic stroke. This study aimed to detect the correlation between OSA severity and post-stroke depression (PSD) in ischemic stroke patients. METHODS: From Mar 2017 to Dec 2018, 265 patients with symptom onset less than 14 days were consecutively recruited. All patients underwent polysomnography examination for diagnosis of OSA during hospitalization. PSD was identified using the Chinese version of the Structured Clinical Interview for DSM-IV at admission and 3-month. Logistic regression analyses were performed to assess the association between OSA severity and PSD. RESULTS: Among the 265 patients, the distribution of patients in terms of the OSA severity was as follows: 48 (18.1%) had no OSA, 85 (32.1%) had mild OSA, 54 (20.4%) had moderate OSA, and 78 (29.4%) had severe OSA. Patients diagnosed as PSD at admission and 3-month were 63 (23.8%) and 86 (32.5%), respectively. Univariate analysis showed that reduced OSA severity was correlated with PSD at 3-month (P = 0.003), but not at admission (P = 0.373). In multivariable analysis, after adjustment for covariates, severe OSA (compared with the patients without OSA; odds ratio, 4.04; 95% confidence interval, 1.38-9.62; P = 0.036) was significantly associated with increasing risk of 3-month PSD. Furthermore, multiple-adjusted spline regression model further confirmed a dose-response relationship between apnea-hypopnea index and 3-month PSD (P for linearity < 0.001). CONCLUSIONS: Our data showed that OSA severity was positively associated with 3-month PSD in ischemic stroke patients.

13.
J Hepatol ; 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32437830

RESUMO

BACKGROUND & AIMS: Liver enzyme abnormalities are common in patients with coronavirus disease 2019 (COVID-19). Whether or not severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to liver damage per se remains unknown. Herein, we reported the clinical characteristics and liver pathological manifestations of COVID-19 patients with liver enzyme abnormalities. METHODS: We analyzed 156 patients diagnosed with COVID-19 from 2 designated centers in China and compared clinical features between patients with or without elevated aminotransferases. Postmortem liver biopsies were obtained from 2 cases who had elevated aminotransferases. We investigated the patterns of liver impairment by electron microscopy, immunohistochemistry, TUNEL assay and pathological studies. RESULTS: Sixty-four out of 156 (41.0%) patients with COVID-19 had elevated aminotransferases. The median levels of alanine aminotransferase were 50 U/L vs. 19 U/L, respectively, aspartate aminotransferase were 45.5 U/L vs. 24 U/L, respectively in abnormal and normal aminotransferase groups. Liver enzyme abnormalities were associated with disease severity, as well as a series of laboratory tests including higher alveolar-arterial oxygen partial pressure difference, higher gamma-glutamyltransferase, lower albumin, decreased CD4+ T cells and B lymphocytes. Ultrastructural examination identified typical coronavirus particles, characterized by spike structures, in the cytoplasm of hepatocytes in 2 COVID-19 cases. SARS-CoV-2-infected hepatocytes displayed conspicuous mitochondrial swelling, endoplasmic reticulum dilatation and glycogen granule decrease. Histologically, massive hepatic apoptosis and some binuclear hepatocytes were observed. Taken together, both ultrastructural and histological evidence indicated a typical lesion of viral infection. Immunohistochemical results showed scarce CD4+ and CD8+ lymphocytes. No obvious eosinophil infiltration, cholestasis, fibrin deposition, granuloma, massive central necrosis, or interface hepatitis were observed. CONCLUSIONS: SARS-CoV-2 infection in the liver directly contributes to hepatic impairment in patients with COVID-19. Hence, a surveillance of viral clearance in liver and long-term outcome of COVID-19 is required. LAY SUMMARY: Liver enzyme abnormalities are common in patients with coronavirus disease 2019 (COVID-19). We reported the clinical characteristics and liver pathological manifestations of COVID-19 patients with elevated liver enzymes. Our findings suggested that SARS-CoV-2 infection of the liver is a crucial factor contributing to hepatic impairment in patients with COVID-19.

14.
Exp Biol Med (Maywood) ; 245(11): 983-993, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32408765

RESUMO

IMPACT STATEMENT: Our study provided new insight into the mechanism underlying the preservation of the peritoneum by valsartan. The results demonstrated that the mice receiving chronic high glucose (HG) peritoneal dialysis solution infusion showed a typical feature of peritoneal fibrosis (PF), as well as higher expression of α-smooth muscle actin (α-SMA) and collagen I. In vitro, HG increased the protein expression of α-SMA and collagen I in a dose-dependent manner, while valsartan significantly ameliorated these pathological changes. Interestingly, there was a parallel decrease in the activity of mammalian target of rapamycin complex 1 (mTORC1) and the protein expression levels of α-SMA and collagen I upon treatment with valsartan in vivo and in vitro. Moreover, the mTOR agonist MHY1485 reversed the downregulation of α-SMA and collagen I in vitro, even in the presence of valsartan. Altogether, our findings reported for the first time that valsartan exerts a protective effect against HG-induced PF by inhibiting the activity of the mTORC1 pathway.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32424946

RESUMO

Toroids and helices are fundamental geometrical structures in nature. Polymers can self-assemble into various nanostructures, including both toroids and helices; however, nanostructures combining toroidal and helical morphologies (that is, helical toroids) are rarely observed. A binary system is reported containing polypeptide homopolymer and its block copolymer, which can hierarchically self-assemble into uniform helical nanotoroids in solution. The formation of the helical toroids is a successive two-step process. First, the homopolymers aggregate into fibrils and convolve into toroids, thereby resembling the toroidal condensation of deoxyribonucleic acid (DNA) chains. Second, the block copolymers self-assemble on the homopolymer toroids and result in helical surface patterns. Additionally, the chirality of the surface helical patterns can be varied by the chirality of the polypeptide block copolymers.

16.
JCI Insight ; 5(12)2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32427582

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), has become a pandemic. This study addresses the clinical and immunopathological characteristics of severe COVID-19. METHODS: Sixty-nine patients with COVID-19 were classified into severe and nonsevere groups to analyze their clinical and laboratory characteristics. A panel of blood cytokines was quantified over time. Biopsy specimens from 2 deceased cases were obtained for immunopathological, ultrastructural, and in situ hybridization examinations. RESULTS: Circulating cytokines, including IL-8, IL-6, TNF-α, IP10, MCP1, and RANTES, were significantly elevated in patients with severe COVID-19. Dynamic IL-6 and IL-8 were associated with disease progression. SARS-CoV-2 was demonstrated to infect type II and type I pneumocytes and endothelial cells, leading to severe lung damage through cell pyroptosis and apoptosis. In severe cases, lymphopenia, neutrophilia, depletion of CD4+ and CD8+ T lymphocytes, and massive macrophage and neutrophil infiltrates were observed in both blood and lung tissues. CONCLUSIONS: A panel of circulating cytokines could be used to predict disease deterioration and inform clinical interventions. Severe pulmonary damage was predominantly attributed to both cytopathy caused by SARS-CoV-2 and immunopathologic damage. Strategies that prohibit pulmonary recruitment and overactivation of inflammatory cells by suppressing cytokine storm might improve the outcomes of patients with severe COVID-19.


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/patologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/patologia , Adulto , Idoso , Betacoronavirus/isolamento & purificação , Biópsia , Linfócitos T CD8-Positivos , Quimiocina CCL2/sangue , Quimiocina CCL5/sangue , China/epidemiologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Citocinas/sangue , Progressão da Doença , Células Endoteliais/patologia , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Contagem de Linfócitos , Linfopenia/patologia , Linfopenia/virologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia
17.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(1): 125-130, 2020 Jan 30.
Artigo em Chinês | MEDLINE | ID: mdl-32376561

RESUMO

OBJECTIVE: To investigate the changes in behaviors and brain structural network in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD). METHODS: Twenty patients with iRBD (iRBD group) and 22 healthy control subjects were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn-Yahr staging. Diffusion tensor imaging and graph- theoretical analysis were performed for analyzing the topological characteristics of brain structural networks of the patients, and the correlation between the behavioral changes and the changes in the topological characteristics of the brain networks was analyzed. RESULTS: The UPDRS score was significantly higher in iRBD group than in the healthy control group (P < 0.05). No significant difference was found in small-world attributes between the patients with iRBD and the control subjects (P>0.05). The patients with iRBD exhibited significantly shortened characteristic shortest path length Lp (P < 0.05) and significantly increased global efficiency, local efficiency and assortativity (P < 0.05). Examination of regional topological properties of the brain network revealed abnormal node properties in the frontal, temporal, parietal, occipital, and striatal and limbic lobes in patients with iRBD. The patients also had significantly increased degree centrality of the left pallidum and enhanced nodal efficiency in the left thalamus, superior temporal gyrus, temporal pole and bilateral superior occipital gyrus, bilateral putamens as well as the right gyrus rectus, amygdala, supramarginal gyrus, and middle temporal gyrus. The nodal local efficiency was significantly increased in the left superior frontal gyrus, middle cingulate gyrus, superior parietal gyrus, bilateral fusiform gyrus, right superior motor area, postcentral gyrus and angular gyrus of the patients with iRBD. The nodal shortest path was significantly shortened in the left superior motor area, pallidum, thalamus, superior temporal gyrus, temporal pole, bilateral putamens, bilateral superior occipital gyrus, right rectus gyrus, amygdala, supramarginal gyrus and middle temporal gyrus, and the nodal clustering coefficient was significantly lowered in the left superior occipital gyrus of the patients. In patients with iRBD, the UPDRS I score was positively correlated with the nodal efficiency in the right supramarginal gyrus (r=0.50, P < 0.05) and local nodal efficiency in the right fusiform gyrus (r=0.53, P < 0.05), and negatively correlated with the nodal clustering coefficient in the left superior occipital gyrus (r=-0.552, P < 0.05). CONCLUSIONS: Patients with iRBD present with abnormal changes in mental condition, behaviors, emotions, activities of daily living and motor functions. The brain structural network of patient with iRBD still has a small-world property with abnormal global topological property and abnormal distribution of local topological property in the cortex, striatum and limbic system.


Assuntos
Encéfalo/fisiologia , Transtorno do Comportamento do Sono REM/patologia , Atividades Cotidianas , Idoso , Estudos de Casos e Controles , Imagem de Tensor de Difusão , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
18.
J Neuroinflammation ; 17(1): 150, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375835

RESUMO

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive treatment for ischemic stroke. Astrocytes regulation has been suggested as one mechanism for rTMS effectiveness. But how rTMS regulates astrocytes remains largely undetermined. There were neurotoxic and neuroprotective phenotypes of astrocytes (also denoted as classically and alternatively activated astrocytes or A1 and A2 astrocytes) pertaining to pro- or anti-inflammatory gene expression. Pro-inflammatory or neurotoxic polarized astrocytes were induced during cerebral ischemic stroke. The present study aimed to investigate the effects of rTMS on astrocytic polarization during cerebral ischemic/reperfusion injury. METHODS: Three rTMS protocols were applied to primary astrocytes under normal and oxygen-glucose deprivation/reoxygenation (OGD/R) conditions. Cell survival, proliferation, and phenotypic changes were assessed after 2-day treatment. Astrocytes culture medium (ACM) from control, OGD/R, and OGD/R + rTMS groups were mixed with neuronal medium to culture neurons for 48 h and 7 days, in order to explore the influence on neuronal survival and synaptic plasticity. In vivo, rats were subjected to middle cerebral artery occlusion (MCAO), and received posterior orbital intravenous injection of ACM collected from different groups at reperfusion, and at 3 days post reperfusion. The apoptosis in the ischemic penumbra, infarct volumes, and the modified Neurological Severity Score (mNSS) were evaluated at 1 week after reperfusion, and cognitive functions were evaluated using the Morris Water Maze (MWM) tests. Finally, the 10 Hz rTMS was directly applied to MCAO rats to verify the rTMS effects on astrocytic polarization. RESULTS: Among these three frequencies, the 10 Hz protocol exerted the greatest potential to modulate astrocytic polarization after OGD/R injury. Classically activated and A1 markers were significantly inhibited by rTMS treatment. In OGD/R model, the concentration of pro-inflammatory mediator TNF-α decreased from 57.7 to 23.0 Ñ€g/mL, while anti-inflammatory mediator IL-10 increased from 99.0 to 555.1 Ñ€g/mL in the ACM after rTMS treatment. The ACM collected from rTMS-treated astrocytes significantly alleviated neuronal apoptosis induced by OGD/R injury, and promoted neuronal plasticity. In MCAO rat model, the ACM collected from rTMS treatment decreased neuronal apoptosis and infarct volumes, and improved cognitive functions. The neurotoxic astrocytes were simultaneously inhibited after rTMS treatment. CONCLUSION: Inhibition of neurotoxic astrocytic polarization is a potential mechanism for the effectiveness of high-frequency rTMS in cerebral ischemic stroke.

19.
Cell Death Dis ; 11(5): 312, 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32366855

RESUMO

Tempol (4-hydroxy-2,2,6,6-Tetramethylpiperidine-1-oxyl, TPL), a nitroxide compound, inhibits proliferation and increases the vulnerability of cancer cells to apoptosis induced by cytotoxic agents. However, the molecular mechanism of TPL inhibiting cancer cell proliferation has not been fully understood. In this study, we evaluated the metabolic effect of TPL on cancer cells and explored its cancer therapeutic potential. Extracellular flow assays showed that TPL inhibited cellular basal and maximal oxygen consumption rates of mitochondrial. 13C metabolic flux analysis showed that TPL treatment had minimal effect on glycolysis. However, we found that TPL inhibits glutamine metabolism by interfering with the oxidative tricarboxylic acid cycle (TCA) process and reductive glutamine process. We found that the inhibitory effect of TPL on metabolism occurs mainly on the step from citrate to α-ketoglutarate or vice versa. We also found that activity of isocitrate dehydrogenase IDH1 and IDH2, the key enzymes in TCA, were inhibited by TPL treatment. In xenograft mouse model, TPL treatment reduced tumor growth by inhibiting cellular proliferation of xenograft tumors. Thus, we provided a mechanism of TPL inhibiting cancer cell proliferation by interfering with glutamine utilization that is important for survival and proliferation of cancer cells. The study may help the development of a therapeutic strategy of TPL combined with other anticancer medicines.

20.
Nanomaterials (Basel) ; 10(5)2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32413982

RESUMO

The near-field photolithography system has attracted increasing attention in the micro- and nano-manufacturing field, due to the high efficiency, high resolution, and the low cost of the scheme. Nevertheless, the low quality of the nano-patterns significantly limits the industrial application of this technology. Theoretical calculations showed that the reason for the poor nano-patterns is the sharp attenuation of the surface plasmon polaritons (SPPs) in the photoresist layer. The calculation results suggest that the waveguide mode, which is composed of the chromium-equivalent dielectric layer-aluminum, can facilitate the energy flux density distribution in the photoresist layer, resulting in the enhancement of the field intensity of SPPs in the photoresist layer. This reduces the linewidth of nano-patterns, while it enhances the pattern steepness. Eventually, the focusing energy of the photoresist layer can be improved. The finite-difference time-domain method was employed to simulate and verify the theoretical results. It is found that for the rotational near-field photolithography with 355 nm laser illumination, the linewidths of the nano-patterns with and without the aluminum reflector are 17.54 nm and 65.51 nm, respectively. The robustness of the experimental results implies that the application of the aluminum reflector enhances the focusing effect in the photoresist, which can broaden the application of the near-field photolithography.

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