Objective To investigate the changes of the levels of interleukin(IL)-17 in bronchoalveolar lavage fluid (BALF) of BALB/c mice infected by mycoplasma pneumonia (MP).Methods Sixtyfour BALB/c mice were randomly divided into two groups,normal group (n =32) and MP infected group (n =32).The BALF and lung tissue of two groups were collected after MP infection on day 3,7,14,21,each time 8.HE staining was used to observe the pathological changes of the lung tissue.IL-17 content in BALF was detected by ELISA.Results The inflammatory changes of the lung tissue was the most obvious at 7 day,and had begun to subside at 14 day,disappeared at 21 day after MP infection.IL-17 levels in BALF were (53.783 ±2.218) pg/ml(3 day),(65.913 ± 10.693) pg/ml(7 day),(59.915 ± 8.085) pg/ml(14 day),(57.043 ± 11.997) pg/ml(21 day) in MP infection group,and (46.220 ± 3.260) pg/ml in normal group.BALF IL-17 content increased significantly in MP infection group compared with normal group(P ＜ 0.05).IL-17 content reached its peak on day 7 after MP infection (P ＜ 0.05).Conclusion MP infection increased the level of IL-17 in the mice of BALF,reaching the peak on day 7.MP infection may be involved in airway inflammation in asthma through the IL-17 pathway.

Human and animal alveolar echinococcosis (AE) are important helminth infections endemic in wide areas of the Northern hemisphere. Monitoring Echinococcus multilocularis viability and spread using real-time fluorescent imaging in vivo provides a fast method to evaluate the load of parasite. Here, we generated a kind of fluorescent protoscolices in vivo imaging model and utilized this model to assess the activity against E. multilocularis protoscolices of metformin (Met). Results indicated that JC-1 tagged E. multilocularis can be reliably and confidently used to monitor protoscolices in vitro and in vivo. The availability of this transient in vivo fluorescent imaging of E. multilocularis protoscolices constitutes an important step toward the long term bio-imaging research of the AE-infected mouse models. In addition, this will be of great interest for further research on infection strategies and development of drugs and vaccines against E. multilocularis and other cestodes.
Animals ; Cestoda ; Echinococcosis ; Echinococcus multilocularis* ; Echinococcus* ; Helminths ; Humans ; Metformin ; Mice ; Models, Animal ; Parasites ; Vaccines

Human hydatid disease (cystic echinococcosis, CE) is a chronic parasitic infection caused by the larval stage of the cestode Echinococcus granulosus. As the disease mainly affects the liver, approximately 70% of all identified CE cases are detected in this organ. Optical molecular imaging (OMI), a noninvasive imaging technique, has never been used in vivo with the specific molecular markers of CE. Thus, we aimed to construct an in vivo fluorescent imaging mouse model of CE to locate and quantify the presence of the parasites within the liver noninvasively. Drug-treated protoscolices were monitored after marking by JC-1 dye in in vitro and in vivo studies. This work describes for the first time the successful construction of an in vivo model of E. granulosus in a small living experimental animal to achieve dynamic monitoring and observation of multiple time points of the infection course. Using this model, we quantified and analyzed labeled protoscolices based on the intensities of their red and green fluorescence. Interestingly, the ratio of red to green fluorescence intensity not only revealed the location of protoscolices but also determined the viability of the parasites in vivo and in vivo tests. The noninvasive imaging model proposed in this work will be further studied for long-term detection and observation and may potentially be widely utilized in susceptibility testing and therapeutic effect evaluation.
Animals ; Cestoda ; Echinococcosis ; Echinococcus granulosus* ; Echinococcus* ; Fluorescence ; Humans ; In Vitro Techniques ; Liver ; Mice* ; Molecular Imaging ; Parasites

Objective To evaluate the efficacy and safety of single bolus high dose (SD group) ATG-Fresenius induction therapy in kidney transplantation vs.multiple low dose (MD group) administration.Methods A multiple center,prospective,randomized and controlled clinical study was performed on 280 de novo renal transplant recipients from 19 centers.Patients were randomized into 2 groups as follows:SD group,a single high dose (7-9 mg/kg) of ATG-F infused as an induction agent before the vessel anastomoses;MD group,2 mg/kg of ATG-F daily administrated in postoperative 4 days.All the patients accepted maintenance immunosuppressive protocol including tacrolimus,mycophenolate and prednisone.Patients were assessed and data were collected at regular schedule clinic visits on the day 1,3,7,14,30,90,180,270 and 365.The primary end point of efficacy was therapeutic failure rate [the number of death,grafts loss and acute rejection (AR)].The event first occurred should be used in the classification of patients.The non-inferiority evaluation of the two treatment regimens was done based on treatment failure rate.The secondary end points of efficacy were the incidence of AR,delayed graft function (DGF),1-year survival rate of patients and grafts,and serum creatinine at each visiting point.The indicators for safety evaluation included hemotologic variation and incidence of adverse events.Results The therapeutic failure rate in SD group was non-inferior to the MD group (17.24％ vs.23.08％).AR was the major cause of therapeutic failure and there was similar incidence of AR between SD gronp and MD group (12.07％ vs.21.37％).There was no significant difference in the incidence of DGF between SD group and MD group (12.07％ vs.6.84％,P =0.1721).The 1-year patient's survival rate and 1-year graft survival rate in SD group and MD group showed no significant difference (96.55％ vs.98.29％,P =0.6714;94.83％ vs 98.29％,P =0.2750).The serum creatinine level showed no significant differences between two groups at each visit point.There was also no significant difference in total incidence of adverse events between the two groups.In addition,there was also no statistically significant difference in the incidence of concerned and drug-related adverse events between the two groups,including infection,hemotologic abnormality,liver or renal dysfunction,gastrointestinal disorder,etc.After ATG--F administration,peripheral blood lymphocytes in the SD and the MD group immediately decreased but nearly restored to the normal level on the postoperative day 30 and 90 respectively.No severe granulocytopenia,erythropenia or thrombocytopenia occurred in both two groups.Conclusion The efficacy and safety of single high dose of ATG-F induction are non-inferior to multiple low dose ATG-F induction,moreover,single high dose of ATG-F induction is administered more conveniently and economically.

Objective To evaluate the effect of conversion from mycophenolic acid (MPA) to mizoribine (MZR) in renal transplant recipients with gastrointestinal tract (GI) symptoms.Methods A total of 355 renal transplant recipients with GI symptoms caused by MPA administration were enrolled from April 2015 to March 2017 in 25 different renal transplant centers in China.The symptomatic improvement of GI before (baseline) and after conversion to MZR (1,2,4 weeks) was assessed by each item of GI symptoms indication.In addition,the efficacy and safety of the conversion therapy during 12 months were determined.Results Patients showed improvement in GI symptoms including diarrhea,abdominal pain,abdominal distention and stomachache after conversion to MZR 1,2,4 weeks (P＜0.05).In patients with different severity of diarrhea,conversion to MZR therapy significantly improved diarrhea (P＜0.05).During 12 months,no patient experienced clinical immune rejection.We did not observe any infections,leucopenia and other serious side effects.Conclusion MZR could markedly improve GI symptoms caused by MPA administration in renal transplant recipients.

Myocardial injury is a pathological change of myocardium caused by many factors,which can lead to the decline of cardiac function and the occurrence of cardiovascular events.Astragaloside Ⅳ is one of the main pharmacological components in Astragali Radix,which plays an anti-myocardial injury role by regulating various signaling pathways.This article reviewed the anti-myocardial injury mechanism of astragaloside Ⅳ from five aspects:inhibition of oxidative stress,inhibition of apoptosis,anti-myocardial fibrosis,improvement of myocardial energy metabolism and inhibition of myocardium inflammation,in order to provide reference for the mechanism research and clinical application of astragaloside Ⅳ in the prevention and treatment of myocardial injury.

Tacrolimus (TAC), also called FK506, is one of the classical immunosuppressants to prevent allograft rejection after liver transplantation. However, it has been proved to be associated with post-transplant hyperlipemia. The mechanism behind this is unknown, and it is urgent to explore preventive strategies for hyperlipemia after transplantation. Therefore, we established a hyperlipemia mouse model to investigate the mechanism, by injecting TAC intraperitoneally for eight weeks. After TAC treatment, the mice developed hyperlipemia (manifested as elevated triglyceride (TG) and low-density lipoprotein cholesterol (LDL-c), as well as decreased high-density lipoprotein cholesterol (HDL-c)). Accumulation of lipid droplets was observed in the liver. In addition to lipid accumulation, TAC induced inhibition of the autophagy-lysosome pathway (microtubule-associated protein 1 light chain 3β (LC3B) II/I and LC3B II/actin ratios, transcription factor EB (TFEB), protein 62 (P62), and lysosomal-associated membrane protein 1 (LAMP1)) and downregulation of fibroblast growth factor 21 (FGF21) in vivo. Overexpression of FGF21 may reverse TAC-induced TG accumulation. In this mouse model, the recombinant FGF21 protein ameliorated hepatic lipid accumulation and hyperlipemia through repair of the autophagy-lysosome pathway. We conclude that TAC downregulates FGF21 and thus exacerbates lipid accumulation by impairing the autophagy-lysosome pathway. Recombinant FGF21 protein treatment could therefore reverse TAC-caused lipid accumulation and hypertriglyceridemia by enhancing autophagy.
Animals ; Mice ; Tacrolimus ; Liver ; Cholesterol, LDL ; Autophagy ; Disease Models, Animal