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1.
Food Chem ; 337: 127678, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32791429

RESUMO

The sequence and structure of antioxidant peptides play fundamental roles in their antioxidant functions. However, the structural mechanism of antioxidant peptides is still unclear. In this study, we used quantum calculations to reveal the antioxidant mechanism of the peptide PMRGGGGYHY. PMRGGGGYHY has multiple antioxidant active sites, and two tyrosine residues were determined to be the major active sites. Based on the structure-activity relationships of PMRGGGGYHY, the antioxidant activity of the modified peptide significantly improved by 4.8-fold to 9.73 ± 0.61 µmol TE/µmol. In addition, the removal of glycine residues from PMRGGGGYHY would increase the energy of the HOMOs and simplify the hydrogen bonding network, causing a significant increase in antioxidant activity. The intracellular ROS scavenging ability gradually decreased with decreasing glycine content. This same peptide has very different effects in vitro versus as a cellular antioxidant. This paper provides new insights into the structural mechanism and rational design/modification of novel antioxidant peptides.

2.
Analyst ; 145(20): 6447-6455, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33043931

RESUMO

The development of a microplatform with multifunctional integration allowing the dynamic and high-throughput exploration of three-dimensional (3D) cultures is promising for biomedical research. Here, we introduce an integrated microfluidic 3D tumor system with pneumatic manipulation and chemical gradient generation to investigate anticancer therapy in a parallel, controllable, dynamic, and high-throughput manner. The stability of the microfluidic system to realize precise and long-term chemical gradient production was developed. Serial manipulations including active cell trapping, array-like tumor self-assembly and formation, reliable gradient generation, parallel multi-concentration drug stimulation, and real-time tumor analysis were achieved in a single microfluidic device. The microfluidic platform was demonstrated to be stable for high-throughput cell trapping and 3D tumor formation with uniform quantities. On-chip analysis of phenotypic tumor responses to diverse chemotherapies with different concentrations can be conducted in this device. The microfluidic advancement holds great potential for applications in the development of high-performance and multi-functional biomimetic tumor systems and in the fields of cancer research and pharmaceutical development.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33046245

RESUMO

BACKGROUND: The underlying mechanism of viral infection as a risk factor for Parkinson's disease (PD), the second most common neurodegenerative disease, remains unclear. OBJECTIVE: We used Mac-1-/- and gp91phox-/- transgene animal models to investigate the mechanisms by which poly I:C, a mimic of virus double-stranded RNA, induces PD neurodegeneration. METHOD: Poly I:C was stereotaxically injected into the substantia nigra (SN) of wild-type (WT), Mac-1-knockout (Mac-1-/-) and gp91 phox-knockout (gp91 phox-/-) mice (10 µg/µl), and nigral dopaminergic neurodegeneration, α-synuclein accumulation and neuroinflammation were evaluated. RESULT: Dopaminergic neurons in the nigra and striatum were markedly reduced in WT mice after administration of poly I:C together with abundant microglial activation in the SN, and the expression of α-synuclein was also elevated. However, these pathological changes were greatly dampened in Mac-1-/- and gp91 phox-/- mice. CONCLUSIONS: Our findings demonstrated that viral infection could result in the activation of microglia as well as NADPH oxidase, which may lead to neuron loss and the development of Parkinson's-like symptoms. Mac-1 is a key receptor during this process.

4.
PLoS Negl Trop Dis ; 14(10): e0008570, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: covidwho-841536

RESUMO

Little is known about the SARS-CoV-2 contamination of environmental surfaces and air in non-health care settings among COVID-19 cases. We explored the SARS-CoV-2 contamination of environmental surfaces and air by collecting air and swabbing environmental surfaces among 39 COVID-19 cases in Guangzhou, China. The specimens were tested on RT-PCR. The information collected for COVID-19 cases included basic demographic, clinical severity, symptoms at onset, radiological testing, laboratory testing and hospital admission. A total of 641 environmental surfaces and air specimens were collected among 39 COVID-19 cases before disinfection. Among them, 20 specimens (20/641, 3.1%) were tested positive from 9 COVID-19 cases (9/39, 23.1%), with 5 (5/101, 5.0%) positive specimens from 3 asymptomatic cases, 5 (5/220, 2.3%) from 3 mild cases, and 10 (10/374, 2.7%) from 3 moderate cases. All positive specimens were collected within 3 days after diagnosis, and 10 (10/42, 23.8%) were found in toilet (5 on toilet bowl, 4 on sink/faucet/shower, 1 on floor drain), 4 (4/21, 19.0%) in anteroom (2 on water dispenser/cup/bottle, 1 on chair/table, 1 on TV remote), 1 (1/8, 12.5%) in kitchen (1 on dining-table), 1 (1/18, 5.6%) in bedroom (1 on bed/sheet pillow/bedside table), 1 (1/5, 20.0%) in car (1 on steering wheel/seat/handlebar) and 3 (3/20, 21.4%) on door knobs. Air specimens in room (0/10, 0.0%) and car (0/1, 0.0%) were all negative. SARS-CoV-2 was found on environmental surfaces especially in toilet, and may survive for several days. We provided evidence of potential for SARS-CoV-2 transmission through contamination of environmental surfaces.

5.
Sci Rep ; 10(1): 16384, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: covidwho-811563

RESUMO

The COVID-19 outbreak is becoming a public health emergency. Data are limited on the clinical characteristics and causes of death. A retrospective analysis of COVID-19 deaths were performed for patients' clinical characteristics, laboratory results, and causes of death. In total, 56 patients (72.7%) of the decedents (male-female ratio 51:26, mean age 71 ± 13, mean survival time 17.4 ± 8.4 days) had comorbidities. Acute respiratory failure (ARF) and sepsis were the main causes of death. Increases in C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer and lactic acid and decreases in lymphocytes were common laboratory results. Intergroup analysis showed that (1) most female decedents had cough and diabetes. (2) The proportion of young- and middle-aged deaths was higher than elderly deaths for males, while elderly decedents were more prone to myocardial injury and elevated CRP. (3) CRP and LDH increased and cluster of differentiation (CD) 4+ and CD8+ cells decreased significantly in patients with hypertension. The majority of COVID-19 decedents are male, especially elderly people with comorbidities. The main causes of death are ARF and sepsis. Most female decedents have cough and diabetes. Myocardial injury is common in elderly decedents. Patients with hypertension are prone to an increased inflammatory index, tissue hypoxia and cellular immune injury.


Assuntos
Infecções por Coronavirus/mortalidade , Pneumonia Viral/mortalidade , Sepse/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Causas de Morte , China , Comorbidade , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Diabetes Mellitus/epidemiologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Cardiopatias/epidemiologia , Humanos , L-Lactato Desidrogenase/sangue , Ácido Láctico/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Sepse/etiologia , Síndrome Respiratória Aguda Grave/etiologia
6.
Dis Markers ; 2020: 8539804, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33082884

RESUMO

Aim: The success of direct-acting antivirals (DAAs) against hepatitis C virus is a major breakthrough in hepatology. Previous studies have shown that chitinase 3-like protein 1 (CHI3L1) was a marker for staging of liver fibrosis caused by HCV. In this investigation, we used CHI3L1 as a surrogate marker to compare dynamic hepatic fibrosis variations following the elimination of HCV among cases receiving sofosbuvir (SOF)-based regimens and pegylated interferon/ribavirin (PR) treatments. Methods: The study enrolled 105 patients, including 46 SOF-based regimens treated patients, 34 PR-experienced patients, and 25 untreated patients. Serum samples and clinical data were obtained at the baseline, the end of treatment, and at weeks 24 and 48 after treatments. Results: First, we found that serum level of CHI3L1 correlated moderately but significantly with LSM (r = 0.615, P < 0.001) at the baseline, and diagnosed liver cirrhosis at baseline with high accuracy (AUC = 0.939) by ROC analysis. So we explored CHI3L1 as a sensitive biomarker to monitor the regression of liver fibrosis after HCV eradication. We found that the serum CHI3L1 level of CHC cases receiving SOF-based regimen treatments was markedly reduced immediately after treatment compared with that at the baseline (123.79 (118.55) vs. 118.20 (103.68), P = 0.001). For cases undergoing PR treatment, the serum CHI3L1 decreased significantly at week 24 posttreatment compared with that at the baseline (69.98 (51.44) vs 89.15 (110.59), P = 0.016). For the untreated cirrhotic patients, CHI3L1 levels increased at week 96 follow-up compared with that at the baseline (194.73 (172.46) vs. 89.50 (242.97), P = 0.048), reflecting continued worsening of liver fibrosis. Conclusion: CHI3L1 is suggested to be the sensitive marker to monitor fibrosis variations in weeks during treatments and after achieving SVR. It has the potential to allow the identification of early treatment failure for a timely switch to alternative treatment and to allow monitoring progression of fibrosis as a risk factor for liver cirrhosis.

7.
Intern Emerg Med ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: covidwho-871549

RESUMO

BACKGROUND: The worldwide spread of SARS-CoV-2 has infected millions of people leading to over 0.3 million mortalities. The disruption of sodium homeostasis, tends to be a common occurrence in patients with COVID-19. METHODS AND RESULTS: A total of 1,254 COVID-19 patients comprising 124 (9.9%) hyponatremic patients (under 135 mmol/L) and 30 (2.4%) hypernatremic patients (over 145 mmol/L) from three hospitals in Hubei, China, were enrolled in the study. The relationships between sodium balance disorders in COVID-19 patients, its clinical features, implications, and the underlying causes were presented. Hyponatremia patients were observed to be elderly, had more comorbidities, with severe pneumonic chest radiographic findings. They were also more likely to have a fever, nausea, higher leukocyte and neutrophils count, and a high sensitivity C-reactive protein (HS-CRP). Compared to normonatremia patients, renal insufficiency was common in both hyponatremia and hypernatremia patients. In addition, hyponatremia patients required extensive treatment with oxygen, antibiotics, and corticosteroids. The only significant differences between the hypernatremia and normonatremia patients were laboratory findings and clinical complications, and patients with hypernatremia were more likely to use traditional Chinese medicine for treatment compared to normonatremia patients. This study indicates that severity of the disease, the length of stay in the hospital of surviving patients, and mortality were higher among COVID-19 patients with sodium balance disorders. CONCLUSION: Sodium balance disorder, particularly hyponatremia, is a common condition among hospitalized patients with COVID-19 in Hubei, China, and it is associated with a higher risk of severe illness and increased in-hospital mortality.

8.
Biomed Res Int ; 2020: 9549361, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33062706

RESUMO

Background: To evaluate the diagnostic performance of apparent diffusion coefficient (ADC) histogram parameters for differentiating the genetic subtypes in lower-grade diffuse gliomas and explore which segmentation method (ROI-1, the entire tumor ROI; ROI2, the tumor ROI excluding cystic and necrotic portions) performs better. Materials and Methods: We retrospectively evaluated 56 lower-grade diffuse gliomas and divided them into three categories: IDH-wild group (IDHwt, 16cases); IDH mutant with the intact 1p or 19q group (IDHmut/1p19q+, 18cases); and IDH mutant with the 1p/19q codeleted group (IDHmut/1p19q-, 22cases). Histogram parameters of ADC maps calculated with the two different ROI methods: ADCmean, min, max, mode, P5, P10, P25, P75, P90, P95, kurtosis, skewness, entropy, StDev, and inhomogenity were compared between these categories using the independent t test or Mann-Whitney U test. For statistically significant results, a receiver operating characteristic (ROC) curves were constructed, and the optimal cutoff value was determined by maximizing Youden's index. Area under the curve (AUC) results were compared using the method of Delong et al. Results: The inhomogenity from the two different ROI methods for distinguishing IDHwt gliomas from IDHmut gliomas both showed the biggest AUC (0.788, 0.930), the optimal cutoff value was 0.229 (sensitivity, 81.3%; specificity, 75.0%) for the ROI-1 and 0.186 (sensitivity, 93.8%; specificity, 82.5%) for the ROI-2, and the AUC of the inhomogenity from the ROI-2 was significantly larger than that from another segmentation, but no significant differences were identified between the AUCs of other same parameters from the two different ROI methods. For the differentiaiton of IDHmut/1p19q- tumors and IDHmut/1p19q+ tumors, with the ROI-1, the ADCmode showed the biggest AUC (AUC: 0.784; sensitivity, 61.1%; specificity, 90.9%), with the ROI-2, and the skewness performed best (AUC, 0.821; sensitivity, 81.8%; specificity, 77.8%), but no significant differences were identified between the AUCs of the same parameters from the two different ROI methods. Conclusion: ADC values analyzed by the histogram method could help to classify the genetic subtypes in lower-grade diffuse gliomas, no matter which ROI method was used. Extracting cystic and necrotic portions from the entire tumor lesions is preferable for evaluating the difference of the intratumoral heterogeneity and classifying IDH-wild tumors, but not significantly beneficial to predicting the 1p19q genotype in the lower-grade gliomas.

9.
Nurs Ethics ; : 969733020952114, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33063597

RESUMO

BACKGROUND: China's ethics committees alone are unable to meet the growing need for human participant protection. Several scandals in recent years indicate weaknesses in the protection of human participants in China. OBJECTIVES: The aim of the study is to summarize the status and problems of human research protection program in China and to explore its establishment proposals at national and hospital levels. RESEARCH DESIGN: To conduct literature retrieval, Chinese National Knowledge Infrastructure, Chinese Biomedical Document Database, and English databases Web of Science and PubMed were searched; laws, guidelines, and regulations were also searched on web by Google and Chinese search engine Baidu. ETHICAL CONSIDERATIONS: No data were collected from human participants, and ethical review was not required. FINDINGS: There are problems for China's Human Research Protection Program, such as weak relevant legal systems, insufficient administrative supervision, and incompetent ethics committee capacities. To fully protect human participants, China should promote the development of Human Research Protection Program, which can formulate ethics-related laws, improve regulations for the protection of the safety and rights of human participants, strengthen supervision, and enforce compensation for human participants. Owing to the frequency with which human participants are recruited in hospitals in China, hospitals can utilize existing ethics committees and establish data and safety monitoring committees, quality control, fund and contract management, and conflict of interest management offices. DISCUSSION: As a growing program, it remains necessary to learn from the experience of developed countries with high ethics standards and reformulate them to fit China's conditions to explore potential future development. The program will also be an experience for other developing countries. CONCLUSION: Human Research Protection Program can strengthen communication and coordination among various hospital departments to effectively protect the rights and welfare of human participants.

10.
Nat Commun ; 11(1): 5033, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024092

RESUMO

Soaring cases of coronavirus disease (COVID-19) are pummeling the global health system. Overwhelmed health facilities have endeavored to mitigate the pandemic, but mortality of COVID-19 continues to increase. Here, we present a mortality risk prediction model for COVID-19 (MRPMC) that uses patients' clinical data on admission to stratify patients by mortality risk, which enables prediction of physiological deterioration and death up to 20 days in advance. This ensemble model is built using four machine learning methods including Logistic Regression, Support Vector Machine, Gradient Boosted Decision Tree, and Neural Network. We validate MRPMC in an internal validation cohort and two external validation cohorts, where it achieves an AUC of 0.9621 (95% CI: 0.9464-0.9778), 0.9760 (0.9613-0.9906), and 0.9246 (0.8763-0.9729), respectively. This model enables expeditious and accurate mortality risk stratification of patients with COVID-19, and potentially facilitates more responsive health systems that are conducive to high risk COVID-19 patients.


Assuntos
Infecções por Coronavirus/mortalidade , Aprendizado de Máquina , Pandemias , Pneumonia Viral/mortalidade , Idoso , Betacoronavirus , China/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Medição de Risco , Máquina de Vetores de Suporte
11.
Intern Emerg Med ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064253

RESUMO

BACKGROUND: The worldwide spread of SARS-CoV-2 has infected millions of people leading to over 0.3 million mortalities. The disruption of sodium homeostasis, tends to be a common occurrence in patients with COVID-19. METHODS AND RESULTS: A total of 1,254 COVID-19 patients comprising 124 (9.9%) hyponatremic patients (under 135 mmol/L) and 30 (2.4%) hypernatremic patients (over 145 mmol/L) from three hospitals in Hubei, China, were enrolled in the study. The relationships between sodium balance disorders in COVID-19 patients, its clinical features, implications, and the underlying causes were presented. Hyponatremia patients were observed to be elderly, had more comorbidities, with severe pneumonic chest radiographic findings. They were also more likely to have a fever, nausea, higher leukocyte and neutrophils count, and a high sensitivity C-reactive protein (HS-CRP). Compared to normonatremia patients, renal insufficiency was common in both hyponatremia and hypernatremia patients. In addition, hyponatremia patients required extensive treatment with oxygen, antibiotics, and corticosteroids. The only significant differences between the hypernatremia and normonatremia patients were laboratory findings and clinical complications, and patients with hypernatremia were more likely to use traditional Chinese medicine for treatment compared to normonatremia patients. This study indicates that severity of the disease, the length of stay in the hospital of surviving patients, and mortality were higher among COVID-19 patients with sodium balance disorders. CONCLUSION: Sodium balance disorder, particularly hyponatremia, is a common condition among hospitalized patients with COVID-19 in Hubei, China, and it is associated with a higher risk of severe illness and increased in-hospital mortality.

12.
Sci Rep ; 10(1): 17691, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33077816

RESUMO

Lymphocyte apoptosis appears to play an important role in immunodysfunction in sepsis. We investigated the role of miR-223 in cell proliferation and apoptosis to identify potential target downstream proteins in sepsis. We recruited 143 patients with sepsis and 44 healthy controls from the Chinese PLA General Hospital. Flow cytometry was used to sort monocytes, lymphocytes, and neutrophils from fresh peripheral blood. A miR-223 mimic and inhibitor were used for transient transfection of Jurkat T cells. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to assess expression of the miRNAs in cells. Western blot analysis was performed to measure protein expression. We evaluated the cell cycle and apoptosis by using flow cytometry (FCM) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Expression of miR-223 was significantly higher in the survivor group than in the nonsurvivor group. Multiple linear regression analysis revealed that SOFA scores correlated negatively with miR-223 and monocyte counts, with ß coefficients (95% CI) of - 0.048 (- 0.077, - 0.019) and - 47.707 (- 83.871, - 11.543), respectively. miR-223 expression also correlated negatively with the percentage of apoptosis in lymphocytes. The rate of apoptosis in the miR-223 mimic group was significantly lower than that of the negative control, with an adverse outcome observed in the miR-223 inhibitor group. We also found that miR-223 enhanced the proliferation of Jurkat T cells and that inhibiting miR-223 had an inhibitory effect on the G1/S transition. We conclude that miR-223 can serve as a protective factor in sepsis by reducing apoptosis and enhancing cell proliferation in lymphocytes by interacting with FOXO1. Potential downstream molecules are HSP60, HSP70, and HTRA.

13.
Sci Rep ; 10(1): 16384, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009426

RESUMO

The COVID-19 outbreak is becoming a public health emergency. Data are limited on the clinical characteristics and causes of death. A retrospective analysis of COVID-19 deaths were performed for patients' clinical characteristics, laboratory results, and causes of death. In total, 56 patients (72.7%) of the decedents (male-female ratio 51:26, mean age 71 ± 13, mean survival time 17.4 ± 8.4 days) had comorbidities. Acute respiratory failure (ARF) and sepsis were the main causes of death. Increases in C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer and lactic acid and decreases in lymphocytes were common laboratory results. Intergroup analysis showed that (1) most female decedents had cough and diabetes. (2) The proportion of young- and middle-aged deaths was higher than elderly deaths for males, while elderly decedents were more prone to myocardial injury and elevated CRP. (3) CRP and LDH increased and cluster of differentiation (CD) 4+ and CD8+ cells decreased significantly in patients with hypertension. The majority of COVID-19 decedents are male, especially elderly people with comorbidities. The main causes of death are ARF and sepsis. Most female decedents have cough and diabetes. Myocardial injury is common in elderly decedents. Patients with hypertension are prone to an increased inflammatory index, tissue hypoxia and cellular immune injury.


Assuntos
Infecções por Coronavirus/mortalidade , Pneumonia Viral/mortalidade , Sepse/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Causas de Morte , China , Comorbidade , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Diabetes Mellitus/epidemiologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Cardiopatias/epidemiologia , Humanos , L-Lactato Desidrogenase/sangue , Ácido Láctico/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Sepse/etiologia , Síndrome Respiratória Aguda Grave/etiologia
14.
PLoS Negl Trop Dis ; 14(10): e0008570, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33035211

RESUMO

Little is known about the SARS-CoV-2 contamination of environmental surfaces and air in non-health care settings among COVID-19 cases. We explored the SARS-CoV-2 contamination of environmental surfaces and air by collecting air and swabbing environmental surfaces among 39 COVID-19 cases in Guangzhou, China. The specimens were tested on RT-PCR. The information collected for COVID-19 cases included basic demographic, clinical severity, symptoms at onset, radiological testing, laboratory testing and hospital admission. A total of 641 environmental surfaces and air specimens were collected among 39 COVID-19 cases before disinfection. Among them, 20 specimens (20/641, 3.1%) were tested positive from 9 COVID-19 cases (9/39, 23.1%), with 5 (5/101, 5.0%) positive specimens from 3 asymptomatic cases, 5 (5/220, 2.3%) from 3 mild cases, and 10 (10/374, 2.7%) from 3 moderate cases. All positive specimens were collected within 3 days after diagnosis, and 10 (10/42, 23.8%) were found in toilet (5 on toilet bowl, 4 on sink/faucet/shower, 1 on floor drain), 4 (4/21, 19.0%) in anteroom (2 on water dispenser/cup/bottle, 1 on chair/table, 1 on TV remote), 1 (1/8, 12.5%) in kitchen (1 on dining-table), 1 (1/18, 5.6%) in bedroom (1 on bed/sheet pillow/bedside table), 1 (1/5, 20.0%) in car (1 on steering wheel/seat/handlebar) and 3 (3/20, 21.4%) on door knobs. Air specimens in room (0/10, 0.0%) and car (0/1, 0.0%) were all negative. SARS-CoV-2 was found on environmental surfaces especially in toilet, and may survive for several days. We provided evidence of potential for SARS-CoV-2 transmission through contamination of environmental surfaces.

15.
Biomater Sci ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33016303

RESUMO

Biomimetic nanoparticles have potential applications in many fields due to their favorable properties. Here, we developed a self-adjuvanting biomimetic anti-tumor nanovaccine, which was self-assembled with an amphiphilic conjugate synthesized with the phospholipids of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and hydrophilic Toll-like receptor (TLR9) agonist CpG ODN. The nanovaccine could not only provide effective initial antigen stimulation and sustained long-term antigen supply with a controlled release, but also induce antigen cross-presentation via the MHC-I pathway initiating CD8+ T-cell responses. Moreover, the dense nucleotide shell around the nanovaccine could promote antigen endocytosis via various receptor-mediated pathways into dendritic cells. CpG ODN interacted with TLR9 triggering the cytokine secretion of TNF-α and IL-10, which further boosted the anti-tumor humoral and cellular immune responses, which led to a significant tumor suppressive effect and remarkable survival prolongation. So, this nanovaccine self-assembled with phospholipid-nucleotide amphiphiles can serve as a safe, simple and efficient approach for anti-tumor immunotherapy.

16.
Cancer Sci ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33016509

RESUMO

The prolonged hypersecretion of catecholamine induced by chronic stress may correlate the malignant progression of cancer and ß2-AR overexpressed in certain cancer cells may translate the signals from neuroendocrine system to malignant signals by interacting with oncoproteins, such as Her2. In the present study, we demonstrate that catecholamine stimulation activates the expression and proteolytic activity of ADAM10 by modulating the expression of miR-199a-5p and SIRT1 and also confirm that catecholamine induction triggers the activities of γ-secretase, leading to shedding of Her2 ECD by ADAM10 and subsequent intramembranous cleavage of Her2 ICD by presenilin-dependent γ-secretase, nuclear translocation of Her2 ICD and enhanced transcription of tumor metastasis-associated gene COX-2. Chronic stimulation of catecholamine strongly promotes the invasive activities of cancer cells in vitro and spontaneous tumor lung metastasis in mice. Furthermore, the nuclear localization of Her2 was significantly correlated with overexpression of ß2-AR in human breast caner tissues, indicating that catecholamine-induced ß2-AR activation play decisive roles in tumor metastasis. Our data also reveal that an unknown mechanism by which the regulated intramembrane proteolysis (RIP) initiated by ß2-AR mediated signaling controls a novel Her2-mediated signaling transduction.

17.
Nat Commun ; 11(1): 5033, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: covidwho-834869

RESUMO

Soaring cases of coronavirus disease (COVID-19) are pummeling the global health system. Overwhelmed health facilities have endeavored to mitigate the pandemic, but mortality of COVID-19 continues to increase. Here, we present a mortality risk prediction model for COVID-19 (MRPMC) that uses patients' clinical data on admission to stratify patients by mortality risk, which enables prediction of physiological deterioration and death up to 20 days in advance. This ensemble model is built using four machine learning methods including Logistic Regression, Support Vector Machine, Gradient Boosted Decision Tree, and Neural Network. We validate MRPMC in an internal validation cohort and two external validation cohorts, where it achieves an AUC of 0.9621 (95% CI: 0.9464-0.9778), 0.9760 (0.9613-0.9906), and 0.9246 (0.8763-0.9729), respectively. This model enables expeditious and accurate mortality risk stratification of patients with COVID-19, and potentially facilitates more responsive health systems that are conducive to high risk COVID-19 patients.


Assuntos
Infecções por Coronavirus/mortalidade , Aprendizado de Máquina , Pandemias , Pneumonia Viral/mortalidade , Idoso , Betacoronavirus , China/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Medição de Risco , Máquina de Vetores de Suporte
18.
Medicine (Baltimore) ; 99(40): e22401, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019415

RESUMO

BACKGROUND: A growing body of clinical trials has demonstrated that traditional Chinese medicine Shaoyao Gancao Tang may improve restlessness leg syndrome (RLS). This review aims to systematically assess its effectiveness and safety in the treatment of patients with RLS. METHODS: Eight databases will be searched from the inception to 31 August 2020, including the Chinese Biological Medicine Database, China National Knowledge Infrastructure, Wanfang Database, VIP Information Database, the Cochrane Library, PubMed, EMBASE, and the Web of Science. All published randomized controlled trials that meet the prespecified eligibility criteria will be included. The primary outcomes include the changes in the International Restless Legs Syndrome Rating Scale and the restless sensation assessed by visual analog scales, and the secondary outcomes include effective rate, adverse event rate, quality of life measures, and improvement in the sleep quality index. Study selection, data extraction, and assessment of bias risk will be conducted independently by 2 reviewers. Data synthesis will be carried out with RevMan software (V.5.3.5). Subgroup and sensitivity analysis will be performed when necessary. The strength of the evidence will be assessed by the Grading of Recommendations Assessment, Development and Evaluation System. RESULTS: A high-quality synthesis of current evidence of Shaoyao Gancao Tang's effectiveness and safety for patients with RLS will be provided. CONCLUSION: This systematic review will provide evidence of whether Shaoyao Gancao Tang is an effective and safe intervention for RLS.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Síndrome das Pernas Inquietas/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Medicina Tradicional Chinesa , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Sono/fisiologia
19.
Health Econ ; 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33098348

RESUMO

Since 2010, adult social care spending in England has fallen significantly in real terms whilst demand has risen. Reductions in social care supply may also have impacted demand for NHS services, particularly for those whose care is provided at the interface of the health and care systems. We analyzed a panel dataset of 150 local authorities (councils) to test potential impacts on hospital utilization by people aged 65 and over: emergency admission rates for falls and hip fractures ("front-door" measures); and extended stays of 7 days or longer; and 21 days or longer ("back-door" measures). Changes in social care supply were assessed in two ways: gross current expenditure (per capita 65 and over) adjusted by local labor costs and social care workforce (per capita 18 and over). We ran negative binomial models, controlling for deprivation, ethnicity, age, unpaid care, council class, and year effects. To account for potential endogeneity, we ran instrumental variable regressions and dynamic panel models. Sensitivity analysis explored potential effects of funding for integrated care (the Better Care Fund). There was no consistent evidence that councils with higher per capita spend or higher social care staffing rates had lower hospital admission rates or shorter hospital stays.

20.
Aging Cell ; : e13235, 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33068460

RESUMO

Incidence of intracerebral hemorrhage (ICH) and brain iron accumulation increases with age. Excess iron accumulation in brain tissues post-ICH induces oxidative stress and neuronal damage. However, the mechanisms underlying iron deregulation in ICH, especially in the aged ICH model have not been well elucidated. Ferroportin1 (Fpn) is the only identified nonheme iron exporter in mammals to date. In our study, we reported that Fpn was significantly upregulated in perihematomal brain tissues of both aged ICH patients and mouse model. Fpn deficiency induced by injecting an adeno-associated virus (AAV) overexpressing cre recombinase into aged Fpn-floxed mice significantly worsened the symptoms post-ICH, including hematoma volume, cell apoptosis, iron accumulation, and neurologic dysfunction. Meanwhile, aged mice pretreated with a virus overexpressing Fpn showed significant improvement of these symptoms. Additionally, based on prediction of website tools, expression level of potential miRNAs in ICH tissues and results of luciferase reporter assays, miR-124 was identified to regulate Fpn expression post-ICH. Higher serum miR-124 levels were correlated with poor neurologic scores of aged ICH patients. Administration of miR-124 antagomir enhanced Fpn expression and attenuated iron accumulation in aged mice model. Both apoptosis and ferroptosis, but not necroptosis, were regulated by miR-124/Fpn signaling manipulation. Our study demonstrated the critical role of miR-124/Fpn signaling in iron metabolism and neuronal death post-ICH in aged murine model. Thus, Fpn upregulation or miR-124 inhibition might be promising therapeutic approachs for this disease.

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