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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 266: 120409, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-34607091

RESUMO

Biothiols play an important role in many physiological and pathological processes, especially in the occurrence of oxidative stress caused by abnormal cysteine (Cys) concentration. Therefore, it is particularly critical to develop a method that can specifically identify Cys to avoid interference from other biological analytes. However, most Cys-specific fluorescent probes are difficult to distinguish between homocysteine (Hcy) and glutathione (GSH). In this work, to avoid the interference of Hcy and GSH, we developed a fluorescent probe triarylimidazole-naphthalimide-piperazine-sulfonyl benzoxadiazole (TNP-SBD-Cl) based on fluorescence resonance energy transfer (FRET) on platform of naphthalimide-sulfonyl benzoxadiazole (SBD), the main SBD 4-chlorine groups have mild reactivity to undergo substitution and rearrangement to distinguish Hcy and GSH. The TNP-SBD-Cl response to Cys would turn on FRET and generate a new yellow fluorescence with a large Stokes shift (157 nm), and with excellent selectivity and low detection limit (0.87 µM). Moreover, TNP-SBD-Cl can be used to monitor Cys in living HeLa cells with low cytotoxicity, suggesting that it has markedly diagnostic significance in physiological and pathological processes.


Assuntos
Cisteína , Corantes Fluorescentes , Glutationa , Células HeLa , Homocisteína , Humanos , Naftalimidas , Imagem Óptica , Espectrometria de Fluorescência
2.
Sci Rep ; 11(1): 21772, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34741085

RESUMO

The presence of disease-specific antigens and autoantibodies in the sera of patients with atherosclerosis-related diseases has been widely reported and is considered to result from inflammation of the arterial wall and the involvement of immune factors. The aim of this study was to identify a novel antibody in patients with ischemic stroke by serological identification of antigens using recombinant cDNA expression cloning from patients who had a transient ischemic attack (TIA). We identified the serpin peptidase inhibitor, clade E member 1 (SERPINE1), as a candidate antigen. The serum anti-SERPINE1 antibody levels quantified using amplified luminescent proximity homogeneous assay-linked immunosorbent assay were significantly higher in patients with ischemic stroke, including those with acute cerebral infarction (aCI), TIA, and chronic cerebral infarction, than in healthy donors. The antibody levels were strongly associated with old age, female sex, and presence of hypertension, diabetes mellitus, and cardiovascular disease. Age and intima-media thickness of the carotid artery were positively correlated with antibody levels, which suggests that SERPINE1 may reflect the progression of atherosclerosis. In a multivariate analysis, SERPINE1 antibody level was an independent predictor of aCI. Thus, the serum levels of anti-SERPINE1 antibody could potentially serve as a biomarker of atherothrombotic infarction.

3.
Materials (Basel) ; 14(21)2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34772085

RESUMO

High-temperature components in power plants may fail due to creep and fatigue. Creep damage is usually accompanied by the nucleation, growth, and coalescence of grain boundary cavities, while fatigue damage is caused by excessive accumulated plastic deformation due to the local stress concentration. This paper proposes a multiscale numerical framework combining the crystal plastic frame with the meso-damage mechanisms. Not only can it better describe the deformation mechanism dominated by creep from a microscopic viewpoint, but also reflects the local damage of materials caused by irreversible microstructure changes in the process of creep-fatigue deformation to some extent. In this paper, the creep-fatigue crack initiation analysis of a modified 12%Cr steel (X12CrMoWvNBN10-1-1) is carried out for a given notch specimen. It is found that creep cracks usually initiate at the triple grain boundary junctions or at the grain boundaries approximately perpendicular to the loading direction, while fatigue cracks always initiate from the notch surface where stress is concentrated. In addition to this, the crack initiation life can be quantitatively described, which is affected by the average grain size, initial notch size, stress range and holding time.

4.
Biosens Bioelectron ; 196: 113743, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34740115

RESUMO

Lipoproteins are composed of lipid and apolipoproteins in conjunction with noncovalent bonds. Different lipoprotein categories, particularly Low-Density Lipoprotein (LDL), High-Density Lipoprotein (HDL) and Very Low-Density Lipoprotein (VLDL) disagree in roles for the occurrence and development of cardiovascular disease, and their exact discrimination are critically required. Herein, a multiplexed sensor platform combined with an encoder system is introduced for accurate analysis of multiple lipoproteins in complex matrix. Three encoders, i.e., bare AuNPs, AuNPs-anti-LDL aptamer (AuNPs-apt) and AuNPs-non-aptamer DNA (AuNPs-n), facilitate precise discrimination for lipoprotein subclasses at a fairly low level of 0.490 nM. The binding of single-stranded DNA (ssDNA) with AuNPs prevents them from gathering in a relatively higher level of salt. In targets stimuli, the weaker binding between ssDNA and AuNPs is destroyed to certain degrees depending on the differential affinities among DNA, AuNPs, and multifarious proteins. It results in distinct aggregation states of encoders to cause diverse ultraviolet absorption, which may be statistically characterized to achieve highly facile and precise identification for lipoprotein subclasses. Remarkably, LDL at 0.05-37.5 µg/mL could be identified by the encoder system. 11 typical proteins including three lipoprotein subclasses in human serum were also precisely discriminated. Furthermore, the accurate identification of lipoprotein subclasses with different molar ratios from real clinical serum samples were obtained.

5.
Cell Death Discov ; 7(1): 339, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34750369

RESUMO

The uncontrolled inflammatory response caused by a disorder in inflammation resolution is one of the reasons for acute respiratory distress syndrome (ARDS). The macrophage pool markedly expands when inflammatory monocytes, known as recruited macrophages, migrate from the circulation to the lung. The persistent presence of recruited macrophages leads to chronic inflammation in the resolution phase of inflammation. On the contrary, elimination of the recruited macrophages at the injury site leads to the rapid resolution of inflammation. Resolvin D1 (RvD1) is an endogenous lipid mediator derived from docosahexaenoic acid. Mice were administered RvD1 via the tail vein 3 and 4 days after stimulation with lipopolysaccharide. RvD1 reduced the levels of the inflammatory factors in the lung tissue, promoted the anti-inflammatory M2 phenotype, and enhanced the phagocytic function of recruited macrophages to alleviate acute lung injury. We also found that the number of macrophages was decreased in BAL fluid after treatment with RvD1. RvD1 increased the apoptosis of recruited macrophages partly via the FasL-FasR/caspase-3 signaling pathway, and this effect could be blocked by Boc-2, an ALX/PRP2 inhibitor. Taken together, our findings reinforce the concept of therapeutic targeting leading to the apoptosis of recruited macrophages. Thus, RvD1 may provide a new therapy for the resolution of ARDS.

6.
ACS Sens ; 6(11): 4009-4018, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34757720

RESUMO

Mitochondrial membrane potential (ΔΨm) is a key indicator of cell health or injury due to its vital roles in adenosine 5'-triphosphate synthesis. Thus, monitoring ΔΨm is of great significance for the assessment of cell status, diagnosis of diseases, and medicament screening. Cationic fluorescent probes suffer from severe photobleaching or false positive signals due to the luminescence of the probe on non-mitochondria. Herein, we report a lipophilic cationic fluorescent probe [1-methyl-2-(4-(1,2,2-triphenylvinyl)styryl)-ß-naphthothiazol-1-ium trifluoromethanesulfonate (TPE-NT)] with the features of aggregation-induced emission and intramolecular charge transfer for imaging ΔΨm in live cells. TPE-NT is enriched on the surface of the mitochondrial inner membrane due to the negative ΔΨm, and its fluorescence is activated in the high-viscosity microenvironment. The false positive signals of emission from TPE-NT on non-mitochondria are therefore effectively eliminated. Moreover, TPE-NT exhibits a Stokes shift of >200 nm, near-infrared (∼675 nm) emission, excellent photostability, and low cytotoxicity, which facilitate real-time imaging in live cells. Cell imaging confirmed that the probe can rapidly and reliably report mitochondrial depolarization (decrement of ΔΨm) during cell damage caused by CCCP and H2O2 as well as mitochondrial polarization (increment of ΔΨm) by oligomycin. Furthermore, the probe successfully detected the reduction of ΔΨm in these cell models of hypoxia, heat damage, acidification, aging, inflammation, mitophagy, and apoptosis caused by hypoxia, heatstroke, lactate/pyruvate, doxorubicin, lipopolysaccharide, rapamycin, monensin, and nystatin, respectively.

7.
Commun Biol ; 4(1): 1339, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34837057

RESUMO

We combined conventional evidence from longitudinal data in UK Biobank and genetic evidence from Mendelian randomization (MR) approach to infer the causality between sleep behaviors and fracture risk. We found that participants with insomnia showed 6.4% higher risk of fracture (hazard ratio [HR] = 1.064, 95% CI = 1.038-1.090, P = 7.84 × 10-7), falls and bone mineral density (BMD) mediated 24.6% and 10.6% of the intermediary effect; the MR analyses provided the consistent evidence. A U-shape relationship was observed between sleep duration and fracture risk (P < 0.001) with the lowest risk at sleeping 7-8 h per day. The excessive daytime sleepiness and "evening" chronotype were associated with fracture risk in observational study, but the association between chronotype and fracture did not show in MR analyses. We further generated a sleep risk score (SRS) with potential risk factors (i.e., insomnia, sleep duration, chronotype, and daytime sleepiness). We found that the risk of fracture increased with an increasing SRS (HR = 1.087, 95% CI = 1.065-1.111, P = 1.27 × 10-14). Moreover, 17.4% of the fracture cases would be removed if all participants exhibited a healthy sleep pattern. In conclusion, insomnia had a causal effect on fracture, falls had a larger intermediary effect than BMD in this association. Individuals with fracture risk could benefit from the intervention on unhealthy sleep pattern.

8.
Anal Chim Acta ; 1183: 338973, 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34627508

RESUMO

In this study, the application of carbon dots (CDs) modified NaYF4:Yb, Er nanoparticles (UCNPs@CDs) as the fluorescent nanoprobe for simultaneous detection of Fe2+ and Fe3+ was investigated. Fe3+ quantification (5-80 µmol L-1) was achieved, as a result of Fe3+ induced fluorescence quenching of UCNPs@CDs at 434 nm (under the 336 nm excitation). The chelate (Fe2+-phen) formed by Fe2+ and 1,10-phenanthroline had a broad absorption centered at 510 nm, due to inner filter effect (IFE), Fe2+ quantification (4-120 µmol L-1) was achieved as a result of (Fe2+-phen) induced fluorescence quenching of UCNPs@CDs at 545 nm (under the 980 nm excitation). The resultant UCNPs@CDs probe, with excellent anti-interference capability, favorable fluorescence stability, and convincing performance in real sample analysis, showed promising application in simultaneous detection of Fe2+ and Fe3+.


Assuntos
Carbono , Nanopartículas , Íons , Ferro , Espectrometria de Fluorescência
9.
Front Med (Lausanne) ; 8: 659793, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712673

RESUMO

Background: Extracorporeal membrane oxygenation (ECMO) might benefit critically ill COVID-19 patients. But the considerations besides indications guiding ECMO initiation under extreme pressure during the COVID-19 epidemic was not clear. We aimed to analyze the clinical characteristics and in-hospital mortality of severe critically ill COVID-19 patients supported with ECMO and without ECMO, exploring potential parameters for guiding the initiation during the COVID-19 epidemic. Methods: Observational cohort study of all the critically ill patients indicated for ECMO support from January 1 to May 1, 2020, in all 62 authorized hospitals in Wuhan, China. Results: Among the 168 patients enrolled, 74 patients actually received ECMO support and 94 not were analyzed. The in-hospital mortality of the ECMO supported patients was significantly lower than non-ECMO ones (71.6 vs. 85.1%, P = 0.033), but the role of ECMO was affected by patients' age (Logistic regression OR 0.62, P = 0.24). As for the ECMO patients, the median age was 58 (47-66) years old and 62.2% (46/74) were male. The 28-day, 60-day, and 90-day mortality of these ECMO supported patients were 32.4, 68.9, and 74.3% respectively. Patients survived to discharge were younger (49 vs. 62 years, P = 0.042), demonstrated higher lymphocyte count (886 vs. 638 cells/uL, P = 0.022), and better CO2 removal (PaCO2 immediately after ECMO initiation 39.7 vs. 46.9 mmHg, P = 0.041). Age was an independent risk factor for in-hospital mortality of the ECMO supported patients, and a cutoff age of 51 years enabled prediction of in-hospital mortality with a sensitivity of 84.3% and specificity of 55%. The surviving ECMO supported patients had longer ICU and hospital stays (26 vs. 18 days, P = 0.018; 49 vs. 29 days, P = 0.001 respectively), and ECMO procedure was widely carried out after the supplement of medical resources after February 15 (67.6%, 50/74). Conclusions: ECMO might be a benefit for severe critically ill COVID-19 patients at the early stage of epidemic, although the in-hospital mortality was still high. To initiate ECMO therapy under tremendous pressure, patients' age, lymphocyte count, and adequacy of medical resources should be fully considered.

10.
Oncol Lett ; 22(5): 792, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34630703

RESUMO

Previous studies have reported that the aberrant expression of circulating microRNAs (miRNAs/miRs) can be used as diagnostic and prognostic markers in non-small cell lung cancer (NSCLC). The present study aimed to assess the diagnostic and prognostic predictive values of four plasma miRNAs for NSCLC. A total of 12 candidate miRNAs were selected that have previously been reported to be aberrantly expressed in NSCLC, and their plasma levels in the training set were detected via reverse transcription-quantitative PCR analysis. The screened out miRNAs were further validated in the testing set. The area under the curve (AUC) of the receiver operating characteristic curve was constructed to evaluate diagnostic performance. Kaplan-Meier survival analysis was performed to assess the association between the plasma miRNA levels and disease-free survival (DFS) time. The results demonstrated that 4/12 plasma miRNAs (miR-210, miR-1290, miR-150 and miR-21-5p) were highly expressed in patients with NSCLC compared with their expression levels in patients with benign lung disease (BLD) and healthy controls in the training and testing sets, respectively. The AUC values of the four-miRNA panel were 0.96 and 0.93 in the training and testing sets, respectively, for distinguishing patients with NSCLC from healthy controls, which were similar to the AUC values for distinguishing patients with NSCLC from patients with BLD (0.96 and 0.94). The AUC values of the four-miRNA panel in patients with stage I NSCLC were comparable to that of patients with stage II-III NSCLC (0.942 and 0.965). Patients with high plasma levels of miR-210 and miR-150 had worse DFS than those with low plasma levels of these miRNAs. In addition, patients whose plasma levels of the four miRNAs decreased by >50% after surgery exhibited a good DFS. Taken together, the results of the present study suggest that these four miRNAs (miR-210, miR-1290, miR-150 and miR-21-5p) act as useful biomarkers for early diagnosis and prognosis of NSCLC.

11.
Anal Chem ; 93(44): 14900-14906, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34714045

RESUMO

Acetylcholinesterase (AChE) plays crucial roles in the nervous system, and thus the reliable assay of its activity is of great significance for the diagnosis of nervous diseases. In this work, we report a fluorescent sensing platform with silicon quantum dots (Si-QDs) as a fluorescence oscillator and nano iron oxyhydroxide (α-, ß-, and γ-FeOOH) as a quencher for the assay of AChE. FeOOH with α-, ß-, and γ-crystal forms quenches the fluorescence of Si-QDs at λex/λem = 350/438 nm, which is retrieved in the presence of AChE and its substrate acetylthiocholine (ATCh) to provide an off-on strategy with a high signal/noise ratio. It is interesting that the sensitivity of AChE sensing is closely related to the crystal forms of FeOOH, with the highest sensitivity by adopting α-FeOOH as the quencher. A linear calibration is achieved within 0.02-1.4 U/L along with a limit of detection of 0.016 U/L. The sensing strategy was demonstrated by the AChE assay in human blood, plasma, and hemocytes.


Assuntos
Acetilcolinesterase , Pontos Quânticos , Acetiltiocolina , Fluorescência , Humanos , Silício
12.
J Pharmacol Exp Ther ; 379(2): 156-165, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34465632

RESUMO

Acute respiratory distress syndrome (ARDS), a common and fatal clinical condition, is characterized by the destruction of epithelium and augmented permeability of the alveolar-capillary barrier. Resolvin conjugates in tissue regeneration 1 (RCTR1) is an endogenous lipid mediator derived from docosahexaenoic acid , exerting proresolution effects in the process of inflammation. In our research, we evaluated the role of RCTR1 in alveolar fluid clearance (AFC) in lipopolysaccharide-induced ARDS/acute lung injury (ALI) rat model. Rats were injected with RCTR1 (5 µg/kg) via caudal veins 8 hours after lipopolysaccharide (LPS) (14 mg/kg) treatment, and then AFC was estimated after 1 hour of ventilation. Primary type II alveolar epithelial cells were incubated with LPS (1 ug/ml) with or without RCTR1 (10 nM) for 8 hours. Our results showed that RCTR1 significantly enhanced the survival rate, promoted the AFC, and alleviated LPS-induced ARDS/ALI in vivo. Furthermore, RCTR1 remarkably elevated the protein expression of sodium channels and Na, K-ATPase and the activity of Na, K-ATPase in vivo and in vitro. Additionally, RCTR1 also decreased neural precursor cell expressed developmentally downregulated 4-2 (Nedd4-2) level via upregulating Ser473-phosphorylated-Akt expression. Besides this, inhibitors of receptor for lipoxin A4 (ALX), cAMP, and phosphatidylinositol 3-kinase (PI3K) (BOC-2, KH-7, and LY294002) notably inhibited the effects of RCTR1 on AFC. In summary, RCTR1 enhances the protein levels of sodium channels and Na, K-ATPase and the Na, K-ATPase activity to improve AFC in ALI through ALX/cAMP/PI3K/Nedd4-2 pathway, suggesting that RCTR1 may become a therapeutic drug for ARDS/ALI. SIGNIFICANCE STATEMENT: RCTR1, an endogenous lipid mediator, enhanced the rate of AFC to accelerate the resolution of inflammation in the LPS-induced murine lung injury model. RCTR1 upregulates the expression of epithelial sodium channels (ENaCs) and Na, K-ATPase in vivo and in vitro to accelerate the AFC. The efficacy of RCTR1 on the ENaC and Na, K-ATPase level was in an ALX/cAMP/PI3K/Nedd4-2-dependent manner.

13.
Eur Heart J ; 42(42): 4298-4305, 2021 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-34506618

RESUMO

AIMS: This study aimed to assess the clinical characteristics and long-term survival outcome in patients with Takayasu's arteritis-associated pulmonary hypertension (TA-PH). METHODS AND RESULTS: We conducted a nationally representative cohort study of TA-PH using data from the National Rare Diseases Registry System of China. Patients with pulmonary artery involvement who fulfilled the diagnostic criteria of Takayasu's arteritis and pulmonary hypertension were included. The primary outcome was the time from diagnosis of TA-PH to the occurrence of all-cause death. Between January 2007 and January 2019, a total of 140 patients were included, with a mean age of 41.4 years at diagnosis, and a female predominance (81%). Patients with TA-PH had severely haemodynamic and functional impairments at diagnosis. Significant improvements have been found in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and haemodynamic profiles in patients with TA-PH receiving drugs approved for pulmonary arterial hypertension. The overall 1-, 3-, and 5-year survival rates in TA-PH were 94.0%, 83.2%, and 77.2%, respectively. Predictors associated with an increased risk of all-cause death were syncope [adjusted hazard ratio (HR) 5.38 (95% confidence interval 1.77-16.34), P = 0.003], NT-proBNP level [adjusted HR 1.04 (1.03-1.06), P < 0.001], and mean right atrial pressure [adjusted HR 1.07 (1.01-1.13), P = 0.015]. CONCLUSION: Patients with TA-PH were predominantly female and had severely compromised haemodynamics. More than 80% of patients in our cohort survived for at least 3 years. Medical treatment was based on investigators' personal opinions, and no clear risk-to-benefit ratio can be derived from the presented data.


Assuntos
Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Arterite de Takayasu , Adulto , Estudos de Coortes , Feminino , Humanos , Hipertensão Pulmonar/etiologia , Estudos Retrospectivos , Arterite de Takayasu/complicações , Arterite de Takayasu/epidemiologia
14.
Front Oncol ; 11: 708039, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34504788

RESUMO

Background: Esophageal cancer often appears as postoperative metastasis or recurrence after radical surgery. Although we had previously reported that serum programmed cell death ligand 1 (PD-L1) level correlated with the prognosis of esophageal cancer, further novel biomarkers are required for more precise prediction of the prognosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is associated with the cholesterol metabolism. But there was no report of relationship between serum PCSK9 antibody and cancer. Therefore, we investigated whether anti-PCSK9 antibodies could be a novel biomarker for solid cancer. Methods: Serum levels of anti-PCSK9 antibodies and antigens in patients with solid cancer were analyzed using amplified luminescence proximity homogeneous assay-linked immunosorbent assay (AlphaLISA). The reactivity of serum antibodies against recombinant PCSK9 protein was investigated by Western blotting, and the expression of PCSK9 antigens in esophageal cancer tissues was examined by immunohistochemical staining. Results: AlphaLISA showed that serum anti-PCSK9 antibody (s-PCSK9-Ab) levels were significantly higher in patients with esophageal cancer, gastric cancer, colorectal cancer, lung cancer, and breast cancer than in healthy donors, and patients with esophageal cancer had the highest levels. The presence of serum antibody in patients was confirmed by Western blotting. There was no apparent correlation between s-PCSK9-Ab and PCSK9 antigen levels. Immunohistochemical staining demonstrated the expression of PCSK9 antigen in both the cytoplasm and nuclear compartments of esophageal squamous cell carcinoma tissue but not in normal tissue. Compared with patients with low s-PCSK9-Ab levels, those with high s-PCSK9-Ab levels had a favorable postoperative prognosis after radical surgery for esophageal cancer. In the multivariate analysis, tumor depth and s-PCSK9-Ab level were identified as independent prognostic factors. In the univariate analysis of clinicopathological features, high PCSK9 antibody levels were not associated with sex, age, location, tumor depth, lymph node status, squamous cell carcinoma antigen, or p53-Ab, whereas they correlated significantly with PD-L1 levels, which were associated with unfavorable prognosis. Correlation between s-PCSK9-Ab and PD-L1 levels was also confirmed in the logistic regression analysis; therefore, low s-PCSK9-Ab levels could discriminate another poor prognosis group other than high-PD-L1 group. Conclusions: Patients with solid cancer had higher s-PCSK9-Ab levels than healthy donors. High s-PCSK9-Ab levels indicated better prognosis for overall survival after surgery in patients with esophageal cancer.

15.
J Food Sci Technol ; 58(10): 3780-3789, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34471301

RESUMO

This work proposes a novel potential source of antiallergens based on bioactive peptides. Cashew-nut protein hydrolysate with antiallergic activity was prepared from cashew nuts through protease treatment. The change in the antiallergic activity of cashew-nut protein hydrolysate during in vitro simulated digestion was investigated. Cashew-nut protein hydrolysates were prepared through treatment using five different enzymes, namely, Alcalase, Protamex, Neutrase, papain, and bromelin. According to the results of molecular weight distribution, more small molecular weight peptides could be obtained by selecting Alcalase protease than other proteases, and the degree of hydrolysis, trichloroacetic acid-soluble peptide yield and hyaluronidase inhibitory rate of the hydrolysate were 17.0 ± 61.52%, 26.28 ± 0.13% and 62.06% ± 5.07%, which were significantly higher than those of other proteases. Therefore, Alcalase is the most suitable protease for the preparation of cashew-nut hydrolysates. Cashew-nut protein hydrolysates prepared with Alcalase under optimum conditions were fractionated through ultrafiltration. Fractions with low molecular weight exhibited the highest hyaluronidase inhibitory rate (90.57%) among all fractions. The inhibition of hyaluronidase activity during digestion showed that cashew-nut protein hydrolysate III (CPH III) has persistent antiallergic activity. Therefore, CPH III could serve as a potential source of functional peptides with health-promoting effects.

16.
J Alzheimers Dis ; 84(1): 367-375, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34542069

RESUMO

BACKGROUND: Few studies have investigated the association between cognition and brain volume associated with cerebral small vessel disease (CSVD). OBJECTIVE: We investigated the association between cognition and brain volume and neuroimaging markers of CSVD in a community-dwelling population. METHODS: Participants (n = 993, age≥35 years) from the community-based Shunyi Study were included to investigate the association between neuroimaging markers and cognition cross-sectionally. Magnetic resonance imaging markers included brain volume measurements of the total cerebrum, white matter, gray matter, and CSVD imaging markers. Cognitive performance was assessed using neuropsychological tests of the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Fuld Object Memory, digit span, Trail Making Test (TMT)-A, and TMT-B. RESULTS: For brain volume measurement, subcortical white matter fraction was positively associated with MMSE score (ß= 0.034, p = 0.0062) and MoCA score (ß= 0.034, p = 0.0174), and negatively associated with TMT-A and TMT-B completion time (ß= -2.319, p = 0.0002; ß= -2.827, p = 0.0073, respectively). For evaluation of CSVD imaging markers, the presence of lacunes was positively associated with TMT-B completion time (ß= 17.241, p = 0.0028). CONCLUSION: In community-dwelling populations, reduced white matter volumes, as a consequence of aging and vascular damage, are associated with worse global cognition and executive function. Our findings provide potential insights into the correlation between cognition and CSVD-associated subcortical white matter injury.

18.
Zhen Ci Yan Jiu ; 46(7): 610-5, 2021 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-34369683

RESUMO

OBJECTIVE: To observe the effect of tiaoren tongdu acupuncture method (for regulating the function of the Conception Vessel and promoting the circulation of the Governor Vessel) on fractional anisotropy (FA) and upper-extremity motor function after cerebral infarction by diffusion densor imaging (DTI) technology. METHODS: The patients with cerebral infarction were divided into an acupuncture group and a control group according to the random number table method, 27 cases in each group. In the control group, the basic treatment with conventional medication was used. In the acupuncture group, on the basic treatment as the control group, the tiaoren tongdu acupuncture method was provided. Main acupoints included Baihui (GV20), Shuigou(GV26), Chengjiang(CV24), Guanyuan(CV4), Qihai (CV6), Zhongwan (CV12), Shenting(GV24) and Mingmen(GV4). Supplementary points included Jianyu(LI15), Chize(LU5), Houxi (SI3), Weizhong (BL40), Zusanli (ST36) and Taichong (LR3) on the affected side. The needles were retained for 30 min. Acupuncture was given once a day, at the interval of 1 days every week, consecutively for 4 weeks. The upper extremity Fugl-Meyer assessment (UE-FMA) was used to evaluate the motor function of upper extremity before and after treatment. DTI was adopted to observe the FA values of infarct focus, posterior limb of internal capsule (PLIC) and cerebral peduncle on the affected side, as well as FA values at the corresponding parts on the healthy side in the patients of two groups. The relative differences (rFA) were calculated. RESULTS: Compared with their own pretreatment, the UE-FMA value was significantly higher after treatment in either of two groups separately (P<0.05 in the control group, P<0.01 in the acupuncture group). The difference of UE-FMA before and after treatment in the acupuncture group was larger than that in the control group (P<0.05). The FA and rFA values in infarct focus were higher than those before treatment in the two groups (P<0.05). The FA and rFA differences before and after treatment in the infarct focus and PLIC on the affected side were higher in the acupuncture group as compared with the control group (P<0.05). The UE-FMA difference was positively correlated with the rFA difference of each part in either group (P<0.05), and the correlation was the strongest in PLIC on the affected side in either group (P<0.01). CONCLUSION: Tiaoren tongdu acupuncture significantly improves the upper limb movement function after cerebral infarction. The rFA value of PLIC combined with UE-FMA can be used to evaluate the therapeutic effect of acupuncture on the upper extremity movement after cerebral infarction.


Assuntos
Terapia por Acupuntura , Acidente Vascular Cerebral , Pontos de Acupuntura , Anisotropia , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/terapia , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Resultado do Tratamento , Extremidade Superior
19.
Front Mol Biosci ; 8: 670160, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395520

RESUMO

N6-methyladenosine (m6A) modification plays important roles in the pathology of a variety of diseases. However, the roles of m6A modification in sepsis-induced myocardial dysfunction are not well defined. Rats were divided into control and lipopolysaccharide (LPS)-induced sepsis group. Global m6A levels of left ventricle tissue were measured by LC-MS/MS, and transcriptome-wide m6A modifications were profiled using epitranscriptomic microarrays (mRNAs and lncRNAs). Bioinformatics analysis was conducted to understand the functional implications of m6A modifications during sepsis. Methylated lncRNAs and mRNAs were measured by m6A single-base site qPCR. The global m6A levels in left ventricle tissue were significantly decreased in the LPS group. While 27 transcripts (23 mRNAs and four lncRNAs) were hypermethylated, 46 transcripts (39 mRNAs and 7 lncRNAs) were hypomethylated in the LPS group. The mRNA expression of writers and readers was significantly decreased in the LPS group. The m6A modification of Clec1b, Stk38l and Tnfrsf26 was associated with platelet activation and apoptotic pathways. Moreover, the decrease in m6A modification of lncRNA XR_346,771 may be related to cation import in cardiac tissue. Our data provide novel information regarding changes to m6A modifications in cardiac tissue during sepsis, and m6A modifications might be promising therapeutic targets.

20.
Stroke ; 52(12): 3918-3925, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34404235

RESUMO

BACKGROUND AND PURPOSE: Researches on rare variants of NOTCH3 in the general Chinese population are lacking. This study aims to describe the spectrum of rare NOTCH3 variants by whole-exome sequencing in a Chinese community-based cohort and to investigate the association between rare NOTCH3 variants and age-related cerebral small vessel disease. METHODS: The cross-sectional study comprised 1065 participants who underwent whole-exome sequencing and brain magnetic resonance imaging. NOTCH3 variants with minor allele frequency<1% in all 4 public population databases (1000 Genomes, ESP6500siv2_ALL, GnomAD_ALL, and GnomAD_EAS) were defined as rare variants. Multivariable linear and logistic regressions were used to investigate the associations between rare NOTCH3 variants and volume of white matter hyperintensities and cerebral small vessel disease burden. Clinical and imaging characteristics of rare NOTCH3 variant carriers were summarized. RESULTS: Sixty-five rare NOTCH3 variants were identified in 147 of 1065 (13.8%) participants, including 57 missense single nucleotide polymorphisms (SNPs), 5 SNPs in splice branching sites, and 3 frameshift deletions. A significantly higher volume of white matter hyperintensities and heavier burden of cerebral small vessel disease was found in carriers of rare NOTCH3 EGFr (epidermal growth factor-like repeats)-involving variants, but not in carriers of EGFr-sparing variants. The carrying rate of rare EGFr-involving NOTCH3 variants in participants with dementia or stroke was significantly higher than those without dementia or stroke (12.4% versus 6.6%, P=0.041). Magnetic resonance imaging signs suggestive of CADASIL were found in 3.4% (5/145) rare EGFr cysteine-sparing NOTCH3 variant carriers but not in 2 cysteine-altering NOTCH3 variant carriers. CONCLUSIONS: Carriers of rare NOTCH3 variants involving the EGFr domain may be genetically predisposed to age-related cerebral small vessel disease in the general Chinese population.

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