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Pulmonary fibrosis (PF) is a pathological change caused by repeated injuries and repair dysfunction of the alveolar epithelium. Our previous study revealed that the residues Asn3 and Asn4 of peptide DR8 (DHNNPQIR-NH2) could be modified to improve stability and antifibrotic activity, and the unnatural hydrophobic amino acids α-(4-pentenyl)-Ala and d-Ala were considered in this study. DR3penA (DHα-(4-pentenyl)-ANPQIR-NH2) was verified to have a longer half-life in serum and to significantly inhibit oxidative damage, epithelial-mesenchymal transition (EMT) and fibrogenesis in vitro and in vivo. Moreover, DR3penA has a dosage advantage over pirfenidone through the conversion of drug bioavailability under different routes of administration. A mechanistic study revealed that DR3penA increased the expression of aquaporin 5 (AQP5) by inhibiting the upregulation of miR-23b-5p and the mitogen-activated protein kinase (MAPK) pathway, indicating that DR3penA may alleviate PF by regulating MAPK/miR-23b-5p/AQP5. Safety evaluation showed that DR3penA is a peptide drug without obvious toxicity or acute side effects and has significantly improved safety compared to DR8. Thus, our findings suggest that DR3penA, as a novel and low-toxic peptide, has the potential to be a leading compound for PF therapy, which provides a foundation for the development of peptide drugs for fibrosis-related diseases.
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@#The antimicrobial peptide APKGVQGPNG (named YD), a natural peptide originating from Bacillus amyloliquefaciens CBSYD1, exhibited excellent antibacterial and antioxidant properties in vitro. These characteristics are closely related to inflammatory responses which is the central trigger for liver fibrosis. However, the therapeutic effects of YD against hepatic fibrosis and the underlying mechanisms are rarely studied. In this study, we show that YD improved liver function and inhibited the progression of liver fibrosis by measuring the serum transaminase activity and the expression of α-smooth muscle actin and collagen I in carbon tetrachloride-induced mice. Then we found that YD inhibited the level of miR-155, which plays an important role in inflammation and liver fibrosis. Bioinformatics analysis and luciferase reporter assay indicate that Casp12 is a new target of miR-155. We demonstrate that YD significantly decreases the contents of inflammatory cytokines and suppresses the NF-κB signaling pathway. Further studies show that transfection of the miR-155 mimic in RAW264.7 cells partially reversed the YD-mediated CASP12 upregulation, the downregulated levels of inflammatory cytokines, and the inactivation of the NF-κB pathways. Collectively, our study indicates that YD reduces inflammation through the miR-155–Casp12–NF-κB axis during liver fibrosis and provides a promising therapeutic candidate for hepatic fibrosis.
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Objective To explore the protective effect and mechanism of butylphthalide on cerebral ischemia reperfusion injury in mice.Methods The cerebral ischemia reperfusion injury model was established by middle cerebral ischemia occlusion (MCAO).Thirty mice were divided into sham group,ischemia reperfusion group(I/R group) and butylphthalide group (NBP group) with 10 in each group.Neurological defect score and brain infarction volume were detected by TTC to evaluate the treatment effects of butylphthalide.Western blot was used to detect expression of RIP,RIP3 and AIF.Immunocoprecipitation (IP) was used to detect the interaction of AIF and RIP3.Immunofluorescence(IF) was used to detect the nuclear translocation and co-localization of AIF and RIP3.Results Compared with the I/R group,NBP treatment reduced the neurological defect score (I/R:(2.60 ± 0.22),NBP:(1.90 ± 0.23),t =2.18,P＜ 0.05) and brain infarction volume(I/R:(38.32±2.22) ％,NBP:(25.23±2.70) ％,t=3.74,P＜0.01).I/R elevated the expression of RIP1 and RIP3 whereas NBP significantly inhibited the expression of these two proteins (RIP1 (I/R:0.99±0.24,NBP:0.47±0.10,t=2.71,P＜0.05);RIP3 (I/R:0.52±0.17,NBP:0.15±0.04,t=2.87,P＜0.05)).I/R and NBP had no significant effects on the expression of AIF,but the IP results showed that I/R increased the interaction between AIF and RIP3 compared with the sham group.NBP alleviated the interaction between AIF and RIP3.IF results showed that the colocalization and nuclear expression of AIF and RIP3 increased after I/R whereas NBP treatment decreased the effect induced by I/R.Conclusion Butylphthalide alleviated cerebral ischemia reperfusion injury in mice through inhibiting the cell necroptosis.The mechanisms may correlate with decreasing the expression of RIP1 and RIP3 and alleviating the interaction and nuclear translocation of AIF and RIP3.
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Objective To investigate the anesthetic effect and adverse events on different doses of oxyco-done combined with propofol target controlled infusion(TCI)in patients with choledocholithiasis undergoing endo-scopic retrograde cholangio pancreatography(ERCP)with endoscopic sphincterotomy(EST).Methods One hun-dred and twenty patients with choledocholithiasis underwent ERCP with EST in Department of Gastroenterology, Fuzhou General Hospital,from January,2016 to March,2017 were enrolled in this study.Patients were randomly divided into 4 groups(n=30 in each group)including the sufentanil control group(Group A),low dose of oxyco-done group(Group B),moderate dose of oxycodone group(Group C),and high dose of oxycodone group(Group D).Patients in Group A received 0.10 μg/kg intravenous sufentanil,and patients in Group B,C,and D received 0.08 mg/kg,0.10 mg/kg,and 0.12 mg/kg intravenous oxycodone,respectively,at 5 min before induction of gener-al anesthesia followed by propofol TCI. Effect of compartment concentration(Ce)of propofol,mean arterial pres-sure(MAP),and heart rate(HR)at the given time point when patients transferring to operation room(T0),after induction(T1),endoscope through throat(T2),and endoscope through major duodenal papilla(T3)were record-ed.The accumulative dose of propofol,duration of operation,and recovery time were also recorded.Intraoperative sever hypotension,bradycardia,respiratory depression,coughing and moving,and postoperative nausea and vom-iting were recorded. Results Propofol Ce at T1~T3as well as MAP and HR at T2and T3in Group B were signifi-cantly higher than those in Group A,C,and D,respectively(P < 0.05). The accumulative dose of propofol in Group B was more than that in Group A and C,while the accumulative dose of propofol in Group D was less than that in Group A,B,and C,respectively(P<0.01).Recovery time in Group D was longer than that in Group A, B,and C,respectively(P<0.05).Similar incidences of intraoperative sever hypotension,bradycardia,respiratory depression,coughing and moving,and postoperative nausea and vomiting were also observed. Conclusions 0.10 mg/kg intravenous oxycodone at 5 min before induction of general anesthesia combined with propofol TCI presents a favorable anesthetic effect in patients with choledocholithiasis undergoing ERCP with EST without a prolonged recovery time and the increased incidence of adverse events.
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Due to the over negative report of adverse event following immunization (AEFI) by media,some people began to question the safety of vaccination.Date published since 2005 were collected by literature retrieval,mainly including relative AEFI date,current status of media report of AEFI,public awareness about AEFI.Public concern about the vaccination safety mainly focused on the serious diseases which might be caused,influence on immune system.Media' s over negative reactions to AEFI and lack of related knowledge in general public have led to the public' s concern about vaccination safety.Vaccination is the most economical and effective measure for the prevention of diseases and AEFI incidence rate is very low.Therefore,it is necessary for media to give more positive report about vaccination safety.
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Objective To analyze the relationship between N-nitrosodimethylamine (NDMA) and the risk of digestive tract cancers.Methods The papers about the relationship between NDMA and the risk of digestive tract cancers published from 1980 to 2012 were retrieved following databases:Chinese BioMedical Literature Database (CBM),the Chinese Journal Full-text Database (CNKI),Wanfang Database,PubMed and EBSCO.The fix and random effect model was used and statistical analyses were conducted by using RevMan 5.1 software.Results Thirteen papers were found,in which 7 about digestive tract cancers were used in this Meta analysis.The NDMA had significant positive effect on the incidence of digestive tract cancers (RR=1.12,95％ CI:1.03-1.21).The relationship between NDMA and esophageal cancer was not significant (RR =1.18,95 ％CI:0.98-1.41) but NDMA could increase the risk of gastric cancer (RR=1.08,95％ CI:1.00-1.18).For the subtypes of esophageal and gastric cancer,NDMA had positive relationship with esophageal squamous cell carcinoma (RR=l.72,95％ CI:1.01-2.96),but had no significant relationship with esophageal adenocarcinoma,cardiac carcinoma and gastric adenocarcinoma.Conclusion The population-based cohort studies have showed that the NDMA could significantly increase the risk of digestive tract cancers,but the effects differed with subtypes of esophageal and gastric cancer.However,it is necessary to collect more evidence due to the limited studies and obvious differences in the study design,sampling and exposure measurement of these cohort studies.
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Objective To analyze the relationship between N-nitrosodimethylamine (NDMA) and the risk of digestive tract cancers.Methods The papers about the relationship between NDMA and the risk of digestive tract cancers published from 1980 to 2012 were retrieved following databases:Chinese BioMedical Literature Database (CBM),the Chinese Journal Full-text Database (CNKI),Wanfang Database,PubMed and EBSCO.The fix and random effect model was used and statistical analyses were conducted by using RevMan 5.1 software.Results Thirteen papers were found,in which 7 about digestive tract cancers were used in this Meta analysis.The NDMA had significant positive effect on the incidence of digestive tract cancers (RR=1.12,95％ CI:1.03-1.21).The relationship between NDMA and esophageal cancer was not significant (RR =1.18,95 ％CI:0.98-1.41) but NDMA could increase the risk of gastric cancer (RR=1.08,95％ CI:1.00-1.18).For the subtypes of esophageal and gastric cancer,NDMA had positive relationship with esophageal squamous cell carcinoma (RR=l.72,95％ CI:1.01-2.96),but had no significant relationship with esophageal adenocarcinoma,cardiac carcinoma and gastric adenocarcinoma.Conclusion The population-based cohort studies have showed that the NDMA could significantly increase the risk of digestive tract cancers,but the effects differed with subtypes of esophageal and gastric cancer.However,it is necessary to collect more evidence due to the limited studies and obvious differences in the study design,sampling and exposure measurement of these cohort studies.
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<p><b>OBJECTIVE</b>The objective of this study is to review the research on the prognostic markers of idiopathic pulmonary arterial hypertension (IPAH).</p><p><b>DATE SOURCES</b>We searched literature from PubMed and CNKI databases both in English and Chinese up to 2013.</p><p><b>STUDY SELECTION</b>Data about mortality and cut-off value are from clinical trials and identified by analysis.</p><p><b>RESULTS</b>IPAH is an unexplained, progressive, and rare disease characterized by increased pulmonary artery pressure and pulmonary vascular resistance. The diagnosis is difficult, mortality of IPAH is high, and the survival periods are only 2-3 years after diagnosis. Investigations in recent years have identified a range of prognostic markers for IPAH, including the 6-minute walking test, red blood cell distribution width, and platelet levels, as well as imaging findings. Changes in these markers are important sources of information to predict the prognosis of patients with IPAH, which carries significant benefits for treatment planning.</p><p><b>CONCLUSION</b>Even though the prognosis of IPAH has been investigated, the mortality is also high. More accurate and meaningful assessment for the prognosis of IPAH is required.</p>
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Humanos , Biomarcadores , Sangre , Hipertensión Pulmonar Primaria Familiar , Sangre , Metabolismo , Patología , PronósticoRESUMEN
Based on translation research and practice, inspired by focus on image regeneration in poetry translation, this paper advocates the same strategy be used in English translation of Traditional Chinese medical classics, introducing the strategy as Image Equivalence, and demonstrating its advantages in improving translation quality of texts like HuangDi Neijing.
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Objective To determine the serum level of advanced glycosylation end products (AGEs) of uremia and its expression in the vascular wall and peritoneum of dialysis patient, meanwhile to explore its possible significance. Methods Using the ELISA method to determine the serum level of AGEs of uremia; using immunohistochemical method to examine the expression of AGEs in the vascular wall of uremia patients undergoing hemodialysis and the expression of AGEs and laminin in the peritoneum of uremic patients undergoing peritoneal dialysis. Results The AGEs level of uremic patients was obviously higher than that in the normal. No kind of dialysis could clear it well. AGEs accumulated obviously in the vassular wall of hemodialysis patients. After CAPD the expression of AGEs and laminin in the peritoneum was significantly strong. There was an obviously positive correlation between AGEs and laminin, so between these two and the time of peritoneal dialysis. Conclusions The high serum level of AGEs and its accumulation in the vascular wall may relate with the high incidence of cardic diseases of the uremia. Accumulation of AGEs and laminin in the peritoneum of patients undergoing peritoneal dialysis may be one of the reasons causing peritoneum sclerosis and dysultrafiltration