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2.
BMC Neurol ; 22(1): 51, 2022 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-35148711

RESUMO

BACKGROUND: The hyperdense middle cerebral artery sign (HMCAS) is an early radiological marker to provide an early diagnosis and to identify ischemia. As reported, HMCAS is associated with heavy clot burden. Moreover, a heavy clot burden may cause obstruction of the orifices of arteries for leptomeningeal collateral flows and can lead to severe clinical conditions. However, the direct relationship between HMCAS and collateral flows remains unclear. Therefore, we explored the association between HMCAS and leptomeningeal collaterals in patients with acute ischemic stroke. METHODS: Consecutive ischemic stroke patients were enrolled from January 2015 to April 2021. HMCAS appearance and collateral status were detected by multimodal computed tomography at admission. Logistic regression analyses helped to identify the association between HMCAS, collateral flows and stroke severity. RESULTS: In 494 included patients, 180 (36.4%) presented with HMCAS. Ipsilateral collaterals were not seen or less prominent in patients with HMCAS (P < 0.001). The HMCAS appearance was significantly associated with less collaterals (odds ratio 5.17, 95% confidence interval 3.27-8.18, P < 0.001), internal carotid artery + M1/M1 occlusion, the initial stroke severity and follow-up outcomes. Subgroup analyses further confirmed HMCAS as an indicator of poor collaterals in ischemic stroke (all P values < 0.05). CONCLUSIONS: HMCAS is associated with poor leptomeningeal collaterals, the stroke severity and a poor neurological outcome. Therefore, the HMCAS appearance can act as an early warning sign for healthcare professionals to be alert for poor collateral flows and poor neurological outcomes in ischemic stroke patients with middle cerebral artery occlusion.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Humanos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem
3.
Foods ; 11(3)2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35159532

RESUMO

Food contains a variety of poisonous and harmful substances that have an impact on human health. Therefore, food safety is a worldwide public concern. Food detection approaches must ensure the safety of food at every step of the food supply chain by monitoring and evaluating all hazards from every single step of food production. Therefore, early detection and determination of trace-level contaminants in food are one of the most crucial measures for ensuring food safety and safeguarding consumers' health. In recent years, various methods have been introduced for food safety analysis, including classical methods and biomolecules-based sensing methods. However, most of these methods are laboratory-dependent, time-consuming, costly, and require well-trained technicians. To overcome such problems, developing rapid, simple, accurate, low-cost, and portable food sensing techniques is essential. Metal-organic frameworks (MOFs), a type of porous materials that present high porosity, abundant functional groups, and tunable physical and chemical properties, demonstrates promise in large-number applications. In this regard, MOF-based sensing techniques provide a novel approach in rapid and efficient sensing of pathogenic bacteria, heavy metals, food illegal additives, toxins, persistent organic pollutants (POPs), veterinary drugs, and pesticide residues. This review focused on the rapid screening of MOF-based sensors for food safety analysis. Challenges and future perspectives of MOF-based sensors were discussed. MOF-based sensing techniques would be useful tools for food safety evaluation owing to their portability, affordability, reliability, sensibility, and stability. The present review focused on research published up to 7 years ago. We believe that this work will help readers understand the effects of food hazard exposure, the effects on humans, and the use of MOFs in the detection and sensing of food hazards.

4.
Mol Biol Rep ; 2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35179667

RESUMO

BACKGROUND: Oxidative stress in the intervertebral disc leads to nucleus pulposus (NP) degeneration by inducing cell apoptosis. However, the molecular mechanisms underlying this process remain unclear. Increasing evidence indicates that GSK-3ß is related to cell apoptosis induced by oxidative stress. In this study, we explored whether GSK-3ß inhibition protects human NP cell against apoptosis under oxidative stress. METHODS AND RESULTS: Immunofluorescence staining was used to show the expression of GSK-3ß in human NP cells (NPCs). Flow cytometry, mitochondrial staining and western blot (WB) were used to detect apoptosis of treated NPCs, changes of mitochondrial membrane potential and the expression of mitochondrial apoptosis-related proteins using GSK-3ß specific inhibitor SB216763. Co-Immunoprecipitation (Co-IP) was used to demonstrate the interaction between GSK-3ß and Bcl-2. We delineated the protective effect of GSK-3ß specific inhibitor SB216763 on human NPCs apoptosis induced by oxidative stress in vitro. Further, we showed SB216763 exert the protective effect by preservation of the mitochondrial membrane potential and inhibition of caspase 3/7 activity during oxidative injury. The detailed mechanism underlying the antiapoptotic effect of GSK-3ß inhibition was also studied by analyzing mitochondrial apoptosis pathway in vitro. CONCLUSIONS: We concluded that the GSK-3ß inhibitor SB216763 protected mitochondrial membrane potential to delay nucleus pulposus cell apoptosis by inhibiting the interaction between GSK-3ß and Bcl-2 and subsequently reducing cytochrome c(Cyto-C) release and caspase-3 activation. Together, inhibition of GSK-3ß using SB216763 in NPCs may be a favorable therapeutic strategy to slow intervertebral disc degeneration.

5.
Sci Total Environ ; 822: 153439, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35093365

RESUMO

Bisphenol A and its substitutions are commonly used to manufacture epoxy resins, plastic materials and different kinds of daily necessities. In this process, a large number of bisphenol analogues (BPs) are continuously released directly/indirectly into the environment. Through the chain of environment-feed-farmed-animals-livestock and poultry products, BPs present the low concentration but chronic exposure for surroundings and environment. In addition, BPs have been revealed by extensive studies as emerging endocrine disruptors, whose effects on androgens/glucocorticoids have rarely been mentioned in previous reports. The (anta-) agonist/antagonist properties of 18 classic BPs were investigated in vitro: We assessed the cytotoxicity and examined the luciferase induction values of BPs in MDA-kb2 cells, incubated single or co-incubated with dihydrotestosterone (DHT), dexamethasone, flutamide and RU486 for 24 h. From the concentration of 10-10 to 10-5 M, BPs had negligible cytotoxicity for MDA-kb2 cells, except for 4,4'-(9-Fluorenylidene)diphenol with the IC50 1.32 µM. All 18 BPs had the response to androgen/glucocorticoid receptors (AR/GR). BPs at nanomolar and trace concentrations are agonists, while BPs at micromolar and higher concentrations are antagonists. Molecular docking showed that BPs interact with AR/GR through hydrophobic bonds, hydrogen bonds, T-type π-stacking and water-bridge. These experimental data demonstrate the universality of the endocrine-disrupting effects of BPs and suggest the urgency of paying attention to the usages of BPs.


Assuntos
Disruptores Endócrinos , Glucocorticoides , Androgênios , Animais , Compostos Benzidrílicos/toxicidade , Di-Hidrotestosterona , Disruptores Endócrinos/toxicidade , Simulação de Acoplamento Molecular , Fenóis
6.
Neurocrit Care ; 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34981427

RESUMO

BACKGROUND: Early neurological deterioration (END) after endovascular thrombectomy (EVT) is strongly associated with poor prognosis in patients with large vessel occlusion. The relationship between body temperature and END after EVT is unknown, which we aimed to investigate in this study. METHODS: END was defined as an increase of four or more points on the National Institutes of Health Stroke Scale score compared with the baseline assessment within 24 h. Logistic regression and restricted cubic spline models were used to assess the relationship between body temperature and END. RESULTS: Among 7741 consecutive patients with ischemic stroke, 406 patients with large vessel occlusion who underwent EVT were enrolled. In total, 88 (21.7%) patients developed END. Logistic regression showed that the maximum body temperature within 24 h (odds ratio [OR] = 1.97 per °C, 95% confidence interval [CI] 1.17-3.32, p = 0.010) was independently associated with END. This association was nonlinear and J shaped (p for nonlinearity = 0.010), and the risk of END increased when the maximum body temperature within 24 h was lower or higher than 37.0 °C. Fever burden is also independently associated with END (OR = 1.06 per °C × hour, 95% CI 1.01-1.11, p = 0.012). In addition, the timing of fever onset was independently associated with END, and the highest risk of END was associated with fever onset within 6 h after EVT (OR = 3.92, 95% CI 1.25-12.27, p = 0.019). CONCLUSIONS: In summary, there is a J-shaped association between the maximum body temperature within 24 h after EVT and END. Moreover, the risk of END differed according to the timing of fever onset.

7.
Cochrane Database Syst Rev ; 1: CD003654, 2022 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-35000192

RESUMO

BACKGROUND: This is the first update of a review published in 2010. While calcium channel blockers (CCBs) are often recommended as a first-line drug to treat hypertension, the effect of CCBs on the prevention of cardiovascular events, as compared with other antihypertensive drug classes, is still debated. OBJECTIVES: To determine whether CCBs used as first-line therapy for hypertension are different from other classes of antihypertensive drugs in reducing the incidence of major adverse cardiovascular events. SEARCH METHODS: For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials (RCTs) up to 1 September 2020: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2020, Issue 1), Ovid MEDLINE, Ovid Embase, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted the authors of relevant papers regarding further published and unpublished work and checked the references of published studies to identify additional trials. The searches had no language restrictions. SELECTION CRITERIA: Randomised controlled trials comparing first-line CCBs with other antihypertensive classes, with at least 100 randomised hypertensive participants and a follow-up of at least two years. DATA COLLECTION AND ANALYSIS: Three review authors independently selected the included trials, evaluated the risk of bias, and entered the data for analysis. Any disagreements were resolved through discussion. We contacted study authors for additional information. MAIN RESULTS: This update contains five new trials. We included a total of 23 RCTs (18 dihydropyridines, 4 non-dihydropyridines, 1 not specified) with 153,849 participants with hypertension. All-cause mortality was not different between first-line CCBs and any other antihypertensive classes. As compared to diuretics, CCBs probably increased  major cardiovascular events (risk ratio (RR) 1.05, 95% confidence interval (CI) 1.00 to 1.09, P = 0.03) and increased congestive heart failure events (RR 1.37, 95% CI 1.25 to 1.51, moderate-certainty evidence). As compared to beta-blockers, CCBs reduced the following outcomes: major cardiovascular events (RR 0.84, 95% CI 0.77 to 0.92), stroke (RR 0.77, 95% CI 0.67 to 0.88, moderate-certainty evidence), and cardiovascular mortality (RR 0.90, 95% CI 0.81 to 0.99, low-certainty evidence). As compared to angiotensin-converting enzyme (ACE) inhibitors, CCBs reduced stroke (RR 0.90, 95% CI 0.81 to 0.99, low-certainty evidence) and increased congestive heart failure (RR 1.16, 95% CI 1.06 to 1.28, low-certainty evidence). As compared to angiotensin receptor blockers (ARBs), CCBs reduced myocardial infarction (RR 0.82, 95% CI 0.72 to 0.94, moderate-certainty evidence) and increased congestive heart failure (RR 1.20, 95% CI 1.06 to 1.36, low-certainty evidence). AUTHORS' CONCLUSIONS: For the treatment of hypertension, there is moderate certainty evidence that diuretics reduce major cardiovascular events and congestive heart failure more than CCBs. There is low to moderate certainty evidence that CCBs probably reduce major cardiovascular events more than beta-blockers. There is low to moderate certainty evidence that CCBs reduced stroke when compared to angiotensin-converting enzyme (ACE) inhibitors and reduced myocardial infarction when compared to angiotensin receptor blockers (ARBs), but increased congestive heart failure when compared to ACE inhibitors and ARBs. Many of the differences found in the current review are not robust, and further trials might change the conclusions. More well-designed RCTs studying the mortality and morbidity of individuals taking CCBs as compared with other antihypertensive drug classes are needed for patients with different stages of hypertension, different ages, and with different comorbidities such as diabetes.


Assuntos
Hipertensão , Preparações Farmacêuticas , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Humanos , Hipertensão/tratamento farmacológico
8.
BMC Public Health ; 21(1): 2248, 2021 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-34893052

RESUMO

BACKGROUND: Since the outbreak started in 2019, COVID-19 pandemic has a significant global impact. Due to the highly infective nature of SARS-CoV-2, the COVID-19 close contacts are at significant risk of contracting COVID-19. China's experience in successfully controlling COVID-19 emphasized the importance of managing close contacts because this strategy helps to limit potential infection sources, prevent the unconscious spread of COVID-19 and thus control this pandemic. As a result, to understand and consider the management of close contacts may be beneficial to other countries. However, managing close contacts is challenging owing to the huge number of close contacts and a lack of appropriate management tools and literature references. METHODS: A new system called the COVID-19 Close Contact Information Management System was developed. Here we introduced the design, use, improvement and achievements of this system. RESULTS: This system was designed from the standpoint of the Centers for Disease Control and Prevention in charge of managing close contacts. Two main functions and eight modules/themes were ultimately formed after two development stages. The system introduces what information need to be collected in the close contact management. Since the system allows information flow across cities, the geographical distance and administrative regional boundaries are no longer obstacles for managing close contacts, which promotes the management of each close contact. Moreover, when this system is used in conjunction with other data tools, it provides data assistance for understanding the COVID-19 characteristics and formulating targeted COVID-19 control policies. To date, the system has been widely used in Guangdong Province for over 1 year and has recorded tens of thousands of pieces of data. There is sufficient practical experience to suggest that the system is capable of meeting the professional work requirements for close contact management. CONCLUSIONS: This system provides a new way to manage close contacts and restrict the spread of COVID-19 by combining information technology with disease prevention and control strategies in the realm of public health. We hope that this system will serve as an example and guide for those anticipating similar work in other countries in response to current and future public health incidents.


Assuntos
COVID-19 , Humanos , Gestão da Informação , Organizações , Pandemias/prevenção & controle , SARS-CoV-2 , Estados Unidos
9.
Molecules ; 26(22)2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34834090

RESUMO

L-theanine is a nonprotein amino acid found in tea leaves and has been widely used as a safe food additive in beverages or foods because of its varied bioactivities. The aim of this study was to reveal the in vitro gastrointestinal protective effects of L-theanine in DSS-induced intestinal porcine enterocyte (IPEC-J2) cell models using molecular and metabolic methods. Results showed that 2.5% dextran sulfate sodium (DSS) treatment inhibited the cell proliferation of IPEC-J2 and blocked the normal operation of the cell cycle, while L-theanine pretreatment significantly preserved these trends to exert protective effects. L-theanine pre-treatment also up-regulated the EGF, CDC2, FGF2, Rb genes and down-regulated p53, p21 proliferation-related mRNA expression in DSS-treated cells, in accompany with p53 signaling pathway inhibition. Meanwhile, metabolomics analysis revealed that L-theanine and DSS treated IPEC-J2 cells have different metabolomic profiles, with significant changes in the key metabolites involved in pyrimidine metabolism and amino acid metabolism, which play an important role in nucleotide metabolism. In summary, L-theanine has a beneficial protection in DSS-induced IPEC-J2 cells via promoting proliferation and regulating metabolism disorders.


Assuntos
Ciclo Celular/efeitos dos fármacos , Sulfato de Dextrana/farmacologia , Enterócitos/metabolismo , Glutamatos/farmacologia , Inibidores do Crescimento/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Animais , Suínos
10.
J Agric Food Chem ; 69(47): 14192-14203, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34784210

RESUMO

The present study revealed the phylactic effects of l-theanine on a DSS-induced colitis mice model. The results showed that 3% DSS treatment significantly induced intestinal damage as reflected by DAI, histopathological feature, and colon length, while l-theanine pretreatment markedly prevented these trends to exert protective effects. Meanwhile, l-theanine pretreatment decreased the levels of TNF-α, IL-1ß, IL-6, iNOS, and COX2 on DSS-induced colitis. Notably, DSS inhibited the proliferation and promoted the apoptosis of intestinal epithelial cells, thereby damaging the integrity of the intestinal epithelial barrier, whereas l-theanine also played a protective role by attenuating these deteriorated effects. It was also observed that l-theanine treatment downregulated the levels of p-p65, p65, p-p53, p53, and p-AKT protein expression in acute DSS-induced colitis, which showed the protective function of l-theanine, mainly via the NF-κB signaling pathway. Furthermore, the results of lipid analysis and transcriptome analysis show that l-theanine reversed transcriptional profiles and lipid profiles of colitis models, mainly via the inflammatory reactivity-related pathway. Interestingly, the correlation analysis between transcriptional profiles and lipid profiles showed that inflammatory response-related genes were almost significantly correlated with differential lipid metabolites. In summary, l-theanine plays a protective role in DSS-induced colitis via downregulating the NF-κB signaling pathway and regulating lipid metabolism disorders.


Assuntos
Colite , NF-kappa B , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/genética , Colo/metabolismo , Sulfato de Dextrana/metabolismo , Modelos Animais de Doenças , Glutamatos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/genética , Metabolismo dos Lipídeos , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , Transdução de Sinais
11.
Cochrane Database Syst Rev ; 10: CD003654, 2021 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-34657281

RESUMO

BACKGROUND: This is the first update of a review published in 2010. While calcium channel blockers (CCBs) are often recommended as a first-line drug to treat hypertension, the effect of CCBs on the prevention of cardiovascular events, as compared with other antihypertensive drug classes, is still debated. OBJECTIVES: To determine whether CCBs used as first-line therapy for hypertension are different from other classes of antihypertensive drugs in reducing the incidence of major adverse cardiovascular events. SEARCH METHODS: For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials (RCTs) up to 1 September 2020: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2020, Issue 1), Ovid MEDLINE, Ovid Embase, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted the authors of relevant papers regarding further published and unpublished work and checked the references of published studies to identify additional trials. The searches had no language restrictions. SELECTION CRITERIA: Randomised controlled trials comparing first-line CCBs with other antihypertensive classes, with at least 100 randomised hypertensive participants and a follow-up of at least two years. DATA COLLECTION AND ANALYSIS: Three review authors independently selected the included trials, evaluated the risk of bias, and entered the data for analysis. Any disagreements were resolved through discussion. We contacted study authors for additional information. MAIN RESULTS: This update contains five new trials. We included a total of 23 RCTs (18 dihydropyridines, 4 non-dihydropyridines, 1 not specified) with 153,849 participants with hypertension. All-cause mortality was not different between first-line CCBs and any other antihypertensive classes. As compared to diuretics, CCBs probably increased  major cardiovascular events (risk ratio (RR) 1.05, 95% confidence interval (CI) 1.00 to 1.09, P = 0.03) and increased congestive heart failure events (RR 1.37, 95% CI 1.25 to 1.51, moderate-certainty evidence). As compared to beta-blockers, CCBs reduced the following outcomes: major cardiovascular events (RR 0.84, 95% CI 0.77 to 0.92), stroke (RR 0.77, 95% CI 0.67 to 0.88, moderate-certainty evidence), and cardiovascular mortality (RR 0.90, 95% CI 0.81 to 0.99, low-certainty evidence). As compared to angiotensin-converting enzyme (ACE) inhibitors, CCBs reduced stroke (RR 0.90, 95% CI 0.81 to 0.99, low-certainty evidence) and increased congestive heart failure (RR 1.16, 95% CI 1.06 to 1.28, low-certainty evidence). As compared to angiotensin receptor blockers (ARBs), CCBs reduced myocardial infarction (RR 0.82, 95% CI 0.72 to 0.94, moderate-certainty evidence) and increased congestive heart failure (RR 1.20, 95% CI 1.06 to 1.36, low-certainty evidence). AUTHORS' CONCLUSIONS: For the treatment of hypertension, there is moderate certainty evidence that diuretics reduce major cardiovascular events and congestive heart failure more than CCBs. There is low to moderate certainty evidence that CCBs probably reduce major cardiovascular events more than beta-blockers. There is low to moderate certainty evidence that CCBs reduced stroke when compared to angiotensin-converting enzyme (ACE) inhibitors and reduced myocardial infarction when compared to angiotensin receptor blockers (ARBs), but increased congestive heart failure when compared to ACE inhibitors and ARBs. Many of the differences found in the current review are not robust, and further trials might change the conclusions. More well-designed RCTs studying the mortality and morbidity of individuals taking CCBs as compared with other antihypertensive drug classes are needed for patients with different stages of hypertension, different ages, and with different comorbidities such as diabetes.


Assuntos
Hipertensão , Preparações Farmacêuticas , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Humanos , Hipertensão/tratamento farmacológico
12.
Front Neurol ; 12: 635079, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34552547

RESUMO

Background: We aimed to investigate the impact of statin treatment in the acute phase on the risk and severity of post-stroke pneumonia because of the uncertain effects of statins on post-stroke pneumonia. Methods: Consecutive cases of acute ischemic stroke (AIS) between January 2014 and February 2019 were retrospectively analyzed. Additionally, the association of statin treatment in the acute phase with the risk and severity of post-stroke pneumonia was estimated with logistic regression. We registered the present study in the Chinese Clinical Trial Registry (ChiCTR 2000032838). Results: Of the 1,258 enrolled patients, no significant difference was observed in post-stroke pneumonia risk between the two groups (with/without statin treatment in the acute phase) after propensity score matching (35.1 vs. 27.9%, p = 0.155). We did not find statin treatment in the acute phase to significantly increase the risk of post-stroke pneumonia both before and after matched analysis [odds ratio (OR) = 1.51, 95% confidence interval (CI) = 0.85-2.67, p = 0.157; OR = 1.57, 95% CI = 0.77-3.18, p = 0.213, respectively]. In the 271 patients with post-stroke pneumonia, no significant difference was found in its severity between two groups (19.6 vs. 19.4%, p = 0.964). No significant association was found between statin treatment and post-stroke pneumonia severity (OR = 0.95, 95% CI = 0.39-2.31, p = 0.918). Conclusions: There appeared to be no additional benefits of statin treatment in the acute phase for post-stroke pneumonia reduction among AIS patients. Clinical Trial Registration:http://www.chictr.org.cn, identifier: ChiCTR2000032838.

13.
Biomaterials ; 276: 121065, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34391018

RESUMO

Clearance of peripheral amyloid-ß (Aß) has been demonstrated particularly promising for overcoming the blood-brain barrier (BBB) hurdle to remove brain-derived Aß associated with Alzheimer's disease (AD). However, currently used therapeutic agents targeting peripheral Aß cannot simultaneously achieve plasma Aß enrichment and enhanced clearance, which may result in poor bioavailability and rather low efficacy. Moreover, most of therapeutic agents usually promote the unfavorable aggregation of Aß. Herein, we construct a near-infrared (NIR) regulated surface-transformable and target peptide-guided upconversion platform (UCNP/ONA-P/K), serving as a safe and effective way for Aß clearance. Taking advantage of extended blood circulation, high selectivity toward Aß, and surface-transformable property, such UCNP/ONA-P/K can address the challenges of peripheral Aß clearance by a combination of enhancing the enrichment of plasma Aß, preventing the unfavorable aggregation of Aß and simultaneously facilitating the hepatic clearance of the captured Aß. After verified by a series of systematic toxicity evaluation, cell uptake, deep tissue penetration, and hemolytic experiments, in vivo studies demonstrate that UCNP/ONA-P/K can efficiently decrease brain Aß burden and reverse memory deficits in 3xTg-AD mice. Overall, this NIR multi-functional design provides a new biocompatible and efficient way for Aß removal, which will promote the application of peripheral clearance of Aß for AD treatment.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Animais , Transporte Biológico , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Camundongos
14.
Front Aging Neurosci ; 13: 680205, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248605

RESUMO

Background: Increased aortic stiffness has been found to be associated with cognitive function decline, but the evidence is still under debate. It is of great significance to elucidate the evidence in this debate to help make primary prevention decisions to slow cognitive decline in our routine clinical practice. Methods: Electronic databases of PubMed, EMBASE, and Cochrane Library were systematically searched to identify peer-reviewed articles published in English from January 1, 1986, to March 16, 2020, that reported the association between aortic stiffness and cognitive function. Studies that reported the association between aortic pulse wave velocity (PWV) and cognitive function, cognitive impairment, and dementia were included in the analysis. Results: Thirty-nine studies were included in the qualitative analysis, and 29 studies were included in the quantitative analysis. The aortic PWV was inversely associated with memory and processing speed in the cross-sectional analysis. In the longitudinal analysis, the high category of aortic PWV was 44% increased risk of cognitive impairment (OR 1.44; 95% CI 1.24-1.85) compared with low PWV, and the risk of cognitive impairment increased 3.9% (OR 1.039; 95% CI 1.005-1.073) per 1 m/s increase in aortic PWV. Besides, meta-regression analysis showed that age significantly increased the association between high aortic PWV and cognitive impairment risk. Conclusion: Aortic stiffness measured by aortic PWV was inversely associated with memory and processing speed and could be an independent predictor for cognitive impairment, especially for older individuals.

15.
J Headache Pain ; 22(1): 41, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34020588

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) bring about a range of psychological distress and symptom deterioration to headache patients especially to some migraineurs. Compared to migraineurs or normal control, medication overuse headache (MOH) patients are more likely to experience a worse psychological distress and poorer outcome in non-COVID-19 time. However, in COVID-19 pandemic, whether MOH patients would have greater physical and mental symptom deterioration or worse relief of headache symptoms and medications overuse remained unclear. We aim to investigate the impact of COVID-19 on MOH patients to guide for a better management in this study. METHODS: We enrolled MOH patients who were diagnosed and treated at headache clinic of West China Hospital. Information of the pre-pandemic 3 months period and COVID-19 pandemic period was collected. Univariate and multivariate logistic regression were performed to identify independent factors associated with changes in headache symptoms and drug withdrawal. RESULTS: Seventy-eight MOH patients were enrolled into the study ultimately. In comparison to pre-pandemic period, fewer MOH patients reported decreased headache days, intensity and days with acute medications per month during the pandemic. Available access to regular prophylactic medications was significantly associated with a reduction of at least 50% in headache days and decrease in headache intensity per month with respective odds ratios of 39.19 (95% CI 3.75-409.15, P = 0.002) and 10.13 (95% CI 2.33-44.12, P = 0.002). Following abrupt withdrawal and high educational level were both significant factors in decreasing headache intensity. Male sex was significantly associated with decrease in days with acute medication per month during the pandemic (odds ratios 4.78, 95%CI 1.44-15.87, P = 0.011). CONCLUSIONS: Our findings reflect that MOH patients experienced a worse relief of headache symptoms and drug withdrawal during the pandemic. Available access to regular prophylactic medications was the significant independent factor for improvement of headache symptoms. Male sex was significantly associated with decreased days with acute medications per month.


Assuntos
COVID-19 , Transtornos da Cefaleia Secundários , Preparações Farmacêuticas , Analgésicos/efeitos adversos , China/epidemiologia , Estudos Transversais , Cefaleia , Transtornos da Cefaleia Secundários/epidemiologia , Humanos , Masculino , Pandemias , SARS-CoV-2
16.
Angew Chem Int Ed Engl ; 60(28): 15436-15444, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-33960090

RESUMO

Metabolic glycan labeling (MGL) followed by bioorthogonal chemistry provides a powerful tool for tumor imaging and therapy. However, selectively metabolic labeling of cells or tissues of interest remains a challenge. Particularly, owing to tumor heterogeneity including tumor subtypes and interpatient heterogeneity, it is far more difficult to realize tumor-cell-selective metabolic labeling for precise diagnosis. Inspired by nature, we designed azidosugar-functionalized metal-organic frameworks camouflaged with cancer cell membranes to accomplish cancer-cell-selective MGL in vivo. With abundant receptors, this biomimetic platform not only selectively targets homotypic cells but also realizes different breast cancer subtype-selective MGL. Moreover, the endo/lysosomal-escaped ZIF-8 can make azidosugar escape from lysosomes and accelerate its metabolic incorporation. This strategy also takes advantage of cancer-tissue-derived cell membranes, which may have huge potential for personalized diagnosis and therapy.


Assuntos
Produtos Biológicos/química , Imidazóis/química , Estruturas Metalorgânicas/química , Neoplasias/diagnóstico , Produtos Biológicos/metabolismo , Diagnóstico Diferencial , Humanos , Imidazóis/metabolismo , Lisossomos/química , Lisossomos/metabolismo , Estruturas Metalorgânicas/metabolismo , Neoplasias/metabolismo , Polissacarídeos/análise , Polissacarídeos/metabolismo
17.
Org Lett ; 23(9): 3337-3342, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33851852

RESUMO

Two novel diastereoisomeric P-chirogenic phosphine catalysts, i.e., JiaPhos, which can be easily derived from inexpensive and commercially available starting materials in five chemical operations (totally 4.16g scale), are introduced. To our delight, the JiaPhos catalysts display good performance in enantioselective (4 + 2) annulations involving 3-methylene-2-oxindoles and γ-benzyl allenoates, providing a wide range of 3,3'-spirocyclic oxindoles with good efficiency and enantioselectivity.

18.
Food Chem Toxicol ; 152: 112162, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33813062

RESUMO

Difenoconazole, cypermethrin and triazophos are widely used pesticides in agricultural production and frequently detected in foods. The aim of this study was to determine the effect of these pesticides and their mixtures on cell viability, reactive oxygen species (ROS), lactate dehydrogenase (LDH) content, apoptosis rate and DNA fragmentation and synthesis in human hepatocellular carcinoma cells (HepG2). The order of inhibitory effects for the individual pesticides was ranked as difenoconazole > cypermethrin > triazophos. The enhanced expression of caspase-3, caspase-7 and PARP activity was observed in HepG2 cells, which was 1.7, 1.3 and 1.6-fold higher than the control, respectively, along with significant protein cleavage; and induced apoptosis in a concentration-dependent manner. Further, the pesticide mixtures significantly increased ROS level (up to 1.3-fold), induced DNA fragmentation (up to 1.8-fold), inhibited DNA synthesis (up to 53%), and damaged the cells by destroying the cell membrane and producing a large amount of LDH at concentration range of 10-30 µM. Specifically, mixtures containing difenoconazole showed stronger toxicities than individual pesticides, implying higher health risks associated with mixtures. Our results show that three widely used pesticides exhibited cytotoxicity and apoptosis through the ROS-related caspase pathway, providing a basis for evaluation of health risks from pesticide mixtures via food consumption.


Assuntos
Apoptose/efeitos dos fármacos , Dioxolanos/toxicidade , Organotiofosfatos/toxicidade , Praguicidas/toxicidade , Piretrinas/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Triazóis/toxicidade , Caspase 3/metabolismo , Caspase 7/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Hep G2 , Humanos , L-Lactato Desidrogenase/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo
19.
BMJ Open ; 11(3): e043450, 2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33762233

RESUMO

INTRODUCTION: Primary prevention of cardiovascular disease (CVD) and stroke often fails due to poor adherence among patients to evidence-based prevention recommendations. The proper formatting of messages portraying CVD and stroke risks and interventional benefits may promote individuals' perception and motivation, adherence to healthy plans and eventual success in achieving risk control. The main objective of this study is to determine whether risk and intervention communication strategies (gain-framed vs loss-framed and long-term vs short-term contexts) and potential interaction thereof have different effects on the optimisation of adherence to clinical preventive management for the endpoint of CVD risk reduction among subjects with at least one CVD risk factor. METHODS AND ANALYSIS: This trial is designed as a 2×2 factorial, observer-blinded multicentre randomised controlled study with four parallel groups. Trial participants are aged 45-80 years and have at least one CVD risk factor. Based on sample size calculations for primary outcome, we plan to enrol 15 000 participants. Data collection will occur at baseline, 6 months and 1 year after randomisation. The primary outcomes are changes in the estimated 10-year CVD risk, estimated lifetime CVD risk and estimated CVD-free life expectancy from baseline to the 1-year follow-up. ETHICS AND DISSEMINATION: This study received approval from the Ethical Committee of West China Hospital, Sichuan University and will be disseminated via peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04450888.


Assuntos
Doenças Cardiovasculares , Comunicação em Saúde , Acidente Vascular Cerebral , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/prevenção & controle , China , Humanos , Pessoa de Meia-Idade , Motivação , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/prevenção & controle
20.
Curr Neurovasc Res ; 18(1): 4-11, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33719972

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread worldwide and poses a great threat to global health. COVID-19 has also an unneglected effect on migraine patients. Migraine attack frequency is one of the migraine characteristics, and its impact during COVID-19 needs further research. We aimed to evaluate whether migraine attack frequency during the COVID-19 pandemic differed from pre-COVID-19 attack frequency and explore possible influencing factors during the pandemic. METHODS: This prospective cohort study enrolled 187 migraine patients from the Department of Neurology of West China Hospital from October 2019 to December 2019. After the inclusion and exclusion criteria, a total of 157 patients were included. We collected demographic data, clinical characteristics, and epidemiological contact information and followed up on March 2020. Then, paired-samples T-tests, logistic regression and interaction tests were used to analyze the data. RESULTS: We found that the migraine attack frequency was 2.47 ± 1.12 before and 3.54 ± 1.79 during COVID-19 (P<0.0001). Then, we divided patients into two groups based on the difference in migraine attack frequency between the COVID-19 and pre-COVID-19 periods and employed logistic regression analysis. In the logistic regression analysis, divorced status (OR = 6.53, P = 0.0453), good sleep pre-COVID-19 and poor sleep during COVID-19 (OR = 3.11, P = 0.0432) had independent effects on migraine attack frequency during the COVID-19 pandemic. We found no interaction in poor sleep during COVID-19 between various subgroups. CONCLUSION: We found that migraineurs' headache attacks were more frequent during COVID-19 than pre-COVID-19 and that increased migraine attack frequency was independently related to divorced status and poor sleep during COVID-19.


Assuntos
COVID-19 , Transtornos de Enxaqueca/epidemiologia , Pandemias , Sono , Adolescente , Adulto , China/epidemiologia , Estudos de Coortes , Estudos Transversais , Divórcio , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/epidemiologia , Adulto Jovem
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