ABSTRACT
Our previous studies have shown that calcitonin gene-related peptide (CGRP) exerts protective effects on the acute lung injury induced by oxidative stress. This study was aimed to investigate whether autophagy was involved in the protection of CGRP against oxidative stress-induced lung injury in neonatal rats. Newborn Sprague-Dawley (SD) rats were randomly divided into five groups: Control group, oxidative stress model group (Model group), Model + CGRP group, Model + CGRP + Rapamycin (an autophagy agonist) group, and Model + CGRP + LY294002 (an autophagy inhibitor) group. The model of hyperoxia-induced lung injury was established by continuous inhalation of oxygen (FiO2 = 90%-95%) for 14 days in neonatal SD rats. Pathological changes of lung tissue were observed by hematoxylin and eosin (HE) staining, and mean linear intercept (MLI) was measured. The quantitative changes of autophagic vesicles (AV) in type II alveolar epithelial cells (AECII) were measured under the transmission electron microscope. The protein expressions of Caspase-3, Bcl-2, mTOR, and Beclin-1 in lung tissue lysates were detected by Western blot. The results showed that, compared to the Model group at the same time point, the number of AV in AECII and the expression level of Beclin-1 protein of the lung tissue were increased, while the expression level of mTOR protein was decreased, with alleviated pathological changes, reduced MLI value and Caspase-3 protein expression level, increased Bcl-2 protein expression level in the lung tissue of Model + CGRP group. In addition, we found that the protective effect of CGRP on hyperoxia-induced lung injury could be enhanced by autophagy activator Rapamycin and abolished by autophagy inhibitor LY294002. Together, these findings indicate that CGRP could attenuate hyperoxia-induced lung injury in neonatal rats by enhancing autophagy.
Subject(s)
Acute Lung Injury , Calcitonin Gene-Related Peptide , Hyperoxia , Lung Injury , Acute Lung Injury/genetics , Acute Lung Injury/metabolism , Acute Lung Injury/pathology , Animals , Animals, Newborn , Autophagy , Calcitonin/metabolism , Calcitonin Gene-Related Peptide/genetics , Calcitonin Gene-Related Peptide/metabolism , Caspase 3/metabolism , Hyperoxia/metabolism , Hyperoxia/pathology , Lung/pathology , Lung Injury/etiology , Lung Injury/metabolism , Lung Injury/prevention & control , Oxidative Stress , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats , Rats, Sprague-Dawley , Sirolimus/pharmacologyABSTRACT
COVID-19 is a huge threat to global health. Due to the lack of definitive etiological therapeutics currently, effective disease monitoring is of high clinical value for better healthcare and management of the large number of COVID-19 patients. In this study, we recruited 37 COVID-19 patients, collected 176 blood samples upon diagnosis and during treatment, and analyzed cell-free DNA (cfDNA) in these samples. We report gross abnormalities in cfDNA of COVID-19 patients, including elevated GC content, altered molecule size and end motif patterns. More importantly, such cfDNA characteristics reflect patient-specific physiological conditions during treatment. Further analysis on tissue origin tracing of cfDNA reveals frequent tissue injuries in COVID-19 patients, which is supported by clinical diagnoses. Hence, we demonstrate the translational merit of cfDNA as valuable analyte for effective disease monitoring, as well as tissue injury assessment in COVID-19 patients.
ABSTRACT
A novel tungsten-doped CeO2 catalyst was fabricated via the sweet potato starch bio-template spread self-combustion (SSC) method to secure a high NH3-SCR activity. The study focuses on the influence of ignition temperature on the physical structure and redox properties of the synthesized catalyst and the catalytic performance of NOx reduction with NH3. These were quantitatively examined by conducting TG-DSC measurements of the starch gel, XRD analysis for the crystallites, SEM and TEM assessments for the morphology of the catalyst, XPS and H2-TPR measurements for the distribution of cerium and tungsten, and NH3-TPD assessments for the acidity of the catalyst. It is found that the ignition temperature shows an important role in the interaction of cerium and tungsten species, and the optimal ignition temperature is 500 °C. The increase of ignition temperature from 150 °C is beneficial to the interactions of species in the catalyst, depresses the formation of WO3, and refines the cubic CeO2 crystallite. The sample ignited at 500 °C shows the biggest BET surface area, the highest surface concentration of Ce species and molar ratio of Ce3+/(Ce3++Ce4+), and the most abundant surface Brønsted acid sites, which are the possible reasons for the superiority of the NH3-SCR activity. With a high GHSV of 200,000 mL (g h)-1 and the optimal ignition temperature, Ce4W2Oz-500 can achieve a steadily high NOx reduction of 80% or more at a lowered reduction temperature in the range of 250~500 °C.
Subject(s)
Ammonia , Cerium , Catalysis , Oxidation-Reduction , Starch , TemperatureABSTRACT
COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.
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The ongoing of coronavirus disease 2019 (COVID-19) pandemic caused by novel SARS-CoV-2 coronavirus, resulting in economic losses and seriously threating the human health in worldwide, highlighting the urgent need of a stabilized, easily produced and effective preventive vaccine. The SARS-COV-2 spike protein receptor binding region (RBD) plays an important role in the process of viral binding receptor angiotensin-converting enzyme 2 (ACE2) and membrane fusion, making it an ideal target for vaccine development. In this study, we designed three different RBD-conjugated nanoparticles vaccine candidates, RBD-Ferritin (24-mer), RBD-mi3 (60-mer) and RBD-I53-50 (120-mer), with the application of covalent bond linking by SpyTag-SpyCatcher system. It was demonstrated that the neutralizing capability of sera from mice immunized with three RBD-conjugated nanoparticles adjuvanted with AddaVax or Sigma Systerm Adjuvant (SAS) after each immunization was ~8-to 120-fold greater than monomeric RBD group in SARS-CoV-2 pseudovirus and authentic virus neutralization assay. Most importantly, sera from RBD-conjugated NPs groups more efficiently blocked the binding of RBD to ACE2 or neutralizing antibody in vitro, a further proof of promising immunization effect. Besides, high physical stability and flexibility in assembly consolidated the benefit for rapid scale-up production of vaccine. These results supported that our designed SARS-CoV-2 RBD-conjugated nanoparticle was competitive vaccine candidate and the carrier nanoparticles could be adopted as universal platform for future vaccine development.
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Objective@#To compare the efficacy of percutaneous transluminal angioplasty (PTA) and neo-anastomosis in juxta-anastomotic stenosis of autologous arteriovenous fistula (AVF) of diabetic hemodialysis patients.@*Methods@#Diabetic patients with juxta-anastomotic stenosis in Beijing Tsinghua Changgung Hospital from February 2016 to December 2018 were retrospectively analyzed. The clinical data, success rate, patency time of PTA and vascular neo-anastomosis were compared.@*Results@#Thirteen patients received PTA, including 1 case of surgical failure and 1 case of thrombosis, and the success rate was 11/13. Vascular neo-anastomosis were performed in 15 cases, and 13 cases succeeded. The success rate was 13/15, and the success rate between two groups had no significant (P > 0.05). The median patency time was 11(7-12) months and 15(5-22) months (P > 0.05). The volume of bleeding [3(2-4) ml vs. 20(10-40) ml], the length of blood vessel wastage [0 vs. (3.6 ± 1.2) cm] and the operating time [(0.6 ± 0.7) h vs. (1.8 ± 0.5) h] of PTA patients were less than those of vascular neo-anastomosis group, and there were significant differences (P < 0.05).@*Conclusions@#There are no significant differences between PTA and neo-anastomosis with respect to patency. PTA has the advantages of less vascular injury, shorter operation time, less bleeding and can dilate arteries at the same time.
ABSTRACT
compare the efficacy of percutaneous transluminal angioplasty (PTA) and neo-anastomosis in juxta-anastomotic stenosis of autologous arteriovenous fistula (AVF) of diabetic hemodialysis patients. Methods Diabetic patients with juxta-anastomotic stenosis in Beijing Tsinghua Changgung Hospital from February 2016 to December 2018 were retrospectively analyzed. The clinical data, success rate, patency time of PTA and vascular neo-anastomosis were compared. Results Thirteen patients received PTA, including 1 case of surgical failure and 1 case of thrombosis, and the success rate was 11/13. Vascular neo-anastomosis were performed in 15 cases, and 13 cases succeeded. The success rate was 13/15, and the success rate between two groups had no significant (P > 0.05). The median patency time was 11(7-12) months and 15(5-22) months (P>0.05). The volume of bleeding [3(2-4) ml vs. 20(10-40) ml], the length of blood vessel wastage [0 vs. (3.6 ± 1.2) cm] and the operating time [(0.6 ± 0.7) h vs. (1.8 ± 0.5) h] of PTA patients were less than those of vascular neo-anastomosis group, and there were significant differences (P < 0.05). Conclusions There are no significant differences between PTA and neo-anastomosis with respect to patency. PTA has the advantages of less vascular injury, shorter operation time, less bleeding and can dilate arteries at the same time.
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Clinical teaching is the critical stage for medical students turning to qualified doctor.In order to overcome the objective problems of insufficient clinical case resources,using the electronic medical record system to collect cases,the real case library of kidney disease was initially constructed,which was presented in the form of network resources.This case database was applied to assist teaching in the probation of eight year medical students at the undergraduate stage,and the application of the case database was evaluated in the form of questionnaire.It is found that case database is helpful to students' clinical learning,and has the necessity of further improvement and good prospects for popularization.It provides a new idea for clinical teaching.
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BACKGROUND: Carotid-femoral pulse wave velocity in hemodialysis patients is influenced by multiple factors.OBJECTIVE: To explore the carotid-femoral pulse wave velocity (PWVcf) changes and related factors in maintenance hemodialysis (MHD) patients.DESIGN, TIME AND SETTING: Non-randomized control experiment was performed at the Third Hospital of Peking University from January to August 2006.PARTICIPANTS: A total of 66 MHD patients were selected from Third Hospital of Peking University.METHODS: General clinical conditions, biochemical indexes, PWVcf and subjective nutritional state were evaluated. MHD patients were divided into two groups according to the state of nutrition evaluated with SGA: non-malnutrition (n=49), malnutrition group (n=17). The PWVcf of two groups was compared, and one-way and multiple regression analyses were performed to explore PWVcf-relatest factors.MAIN OUTCOME MEASURES: PWVcf, blood albumin and parathyroid hormone.RESULTS: PWVcf was significantly positively correlated with age (r= 0.284, P< 0.05), systolic blood pressure (r= 0.468, P<0. 001), and pulse pressure (r=0.451, P< 0.001), while negatively correlated with prealbumin (r=0.318, P< 0. 05),plasma-albumin (r=0.263, P< 0.05), parathyroid hormone (r=0.167, P< 0.05), serum creatinine (r=0.347, P= 0.004)and transferring (r=0.284, P < 0.05) before dialysis. Multiple regression analysis demonstrated that pulse pressure and parathyroid hormone were independently related with PWVcf. The PWVcf was significantly increased in malnutrition group compared with non-malnutrition group (P < 0.05). CONCLUSION: Pulse pressure is the major clinical determinants of arterial stiffness in patients with MHD independent of conventional risk factors for cardiovascular disease; Malnutrition and atherosclerosis are common complications of MHD,showing close relationship. The PWVcf was significantly increased in malnutrition patients.
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BACKGROUND:Little data have been available concerning function features of arterial elasticity in patients with chronic kidney disease at 2-5 stage not undergoing dialysis.Studies have demonstrated that carotid-femoral pulse wave velocity(PWVcf) can be used to evaluate arterial elasticity.OBJECTIVE:To explore the changes and influential factors of PWVcf in patients with chronic kidney disease.DESIGN,TIME AND SETTING:A non-randomized controlled experiment was performed at the Department of Nephrology,Peking University Third Hospital from January to August 2006.PARTICIPANTS:166 patients with chronic kidney disease and 28 health persons were selected from Peking University Third Hospital.METHODS:The patients were divided into 3 groups based on the Kidney/Dialysis Outcomes Quality Initiative(K/DOQI) guideline for chronic kidney disease:mild group(at stage 1 to 2),moderate group(at stage 3) and severe group(at stage 4 to 5);the healthy people served as control.Body mass,blood pressure,PWVcf and biochemical indicators were determined to calculate glomerular filtration rate and compare the differences.One-way and multiple regression analyses were used to explore related factors of PWVcf.MAIN OUTCOME MEASURES:PWVcf and influential factors.RESULTS:Compared with control group,the patients had significantly higher levels of systolic blood pressure,diastolic blood pressure,pulse pressure and PWVcf(P
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As the combining target with sperms, ZP3 undergoes an important role in the fertilization of oocytes and therefore it has been the focus in studying the mechanism of mammalian. According to the sequence of the zona pellucida 3 gene of Lagurus lagurus (lZP3), three RNA interference recombinant vectors were constructed with pGenesil-1 aiming at lZP3 mRNA by synthesizing oligonucleotides. And then co-transfected into the Hela cells by Lipofectamine2000 and co-injected into the mice by hydrodynamics-based transfection method with the expression vector pCDNA3-lZP3. In order to select the efficient target sites of lZP3 for RNAi, the mRNA expression level of lZP3 gene in Hela cells and the mouse liver was detected by semi-quantative RT-PCR and real-time PCR. Results show that there are 2 interference vectors can interfere of the expression of lZP3 mRNA, and the mRNAs of the exogenous genes expressed in the mouse liver are coincident with those of in Hela cells after co-transfected with the interference vectors and expression vector. It also suggests that the mice can be the experimental materials for selecting the efficiency target sites of the RNA interference.
Subject(s)
Animals , Female , Humans , Mice , Arvicolinae , Genetics , Gene Expression Regulation , HeLa Cells , Liver , Metabolism , RNA Interference , RNA, Messenger , Genetics , Metabolism , Receptors, Cell Surface , Genetics , Reverse Transcriptase Polymerase Chain Reaction , TransfectionABSTRACT
<p><b>OBJECTIVE</b>To study the expression of phosphatase and tensin homology deleted on chromosometen ten (PTEN) protein, a tumor suppressor gene in breast cancer and its correlation with p27(kip1) and cyclin D1 expression.</p><p><b>METHODS</b>PTEN protein expression, p27(kip1) and cyclin D1 protein expression were detected by immunohistochemical method in paraffin sections from 61 women with primary breast cancer. PTEN protein expression was compared with clinico-pathologic parameters as related to p27(kip1) and cyclin D1.</p><p><b>RESULTS</b>PTEN, being shown in the cytoplasm, was negative in 6.6% (4/61), reduced in 41.0% (25/61) and positive in 52.5% (32/61) samples. PTEN expression level was correlated with axillary lymph node status, loss of estrogen receptor stain, recurrence and metastasis. On univariate analysis, the disease-free survival rate of patients with higher PTEN expression (> 50% cells stained) was better than those with lower expression (P = 0.0101). However, there was no correlation between p27(kip1), cyclin D1 expression or PTEN expression.</p><p><b>CONCLUSION</b>PTEN, its lower expression being correlated with poor outcome of breast cancer patients, plays a prominent role in breast cancer. p27(kip1) or cyclin D1 may not be the primary downstream genes of PTEN in breast cancer.</p>
