Antiviral Agents ; administration & dosage ; therapeutic use ; DNA, Viral ; blood ; Hepacivirus ; genetics ; Hepatitis C, Chronic ; drug therapy ; virology ; Humans ; Interferon-alpha ; administration & dosage ; therapeutic use ; Ribavirin ; administration & dosage ; therapeutic use ; Standard of Care

Xenotransplantation can probably overcome the critical shortage of human organ donors for clinical transplantation.Recently,research progresses in the biology of xenograft rejection and zoonotic infections,and the generation of α1,3-galactosyltransferase-deficient pigs have moved this approach closer to clinical application,but immunological rejection is also the primary barrier in the study of xenotransplantation.This review sumarries the research progress of immunological rejection of xenotransplantation,providing some advices for the future of clinical xenotransplantation.

Isoliquiritigenin (ISL) is a flavonoid compound isolated from licorice. It possesses excellent antioxidant and anti-diabetic activities. This study aims to investigate the molecular mechanism underlying the alleviatory effect of ISL on energy metabolism imbalance caused by type 2 diabetes mellitus (T2DM). 8-week-old male C57BL/6J mice were used in in vivo experiments. The high-fat-high-glucose diet combined with intraperitoneal injection of streptozotocin was applied to establish T2DM animal model. All animal experiments were performed in accordance with the Institutional Guidelines of Laboratory Animal Administration issued by the Committee of Ethics at Beijing University of Chinese Medicine. HepG2 cells were used in in vitro experiments. Enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (RT-qPCR) were used to examine the protein and mRNA levels of mitochondrial function-related targets. The levels of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) in HepG2 cells were measured by the flow cytometry. Additionally, the molecular docking of ISL and key target proteins was analyzed. It was found that ISL significantly inhibited the activity of mitochondrial respiratory chain complex I and increased the protein levels of uncoupling protein 2 (UCP2) in the livers of mice and HepG2 cells. It also obviously decreased the ROS levels and increased the MMP levels in cultured HepG2 cells. In addition, ISL promoted mitochondrial biogenesis by activating proliferator-activated receptor gamma co-activator 1α (PGC-1α) and enhanced mitophagy by upregulating Parkin. It also improved mitochondrial fusion by increasing the mRNA and protein levels of mitofusin 2 (MFN2). In conclusion, ISL alleviates energy metabolism imbalance caused by T2DM through suppression of excessive mitochondrial oxidative phosphorylation and promotion of mitochondrial biogenesis, mitophagy, and fusion.

Isoliquiritigenin (ISL) is an active chalcone compound isolated from licorice. It possesses anti-inflammatory and anti-oxidative activities. In our previous study, we uncovered a great potential of ISL in treatment of type 2 diabetes mellitus (T2DM). Therefore, this study aims to reveal the mechanism underlying the alleviatory effects of ISL on T2DM-induced glycolipid metabolism disorder. High-fat-high-sugar diet (HFD) combined with intraperitoneal injection of streptozotocin (STZ) were used to establish T2DM mice model. All animal experiments were carried out with approval of the Committee of Ethics at Beijing University of Chinese Medicine. HepG2 cells were used in in vitro experiments, and sodium palmitate (SP) was applied to establish insulin resistance (IR) model cells. The effects of ISL on body weight, fasting blood glucose levels, and pathological changes in the livers of mice were examined. Enzyme-linked immune sorbent assay (ELISA) and real-time quantitative PCR (RT-qPCR) were applied to detect the regulatory effects of ISL on key targets involved in glucolipid metabolism. Additionally, molecular docking and analytical dynamics simulation methods were used to analyze the interaction between ISL and key target protein. The results indicate that ISL significantly downregulates the transcriptional levels and inhibits the activities of key enzymes involved in gluconeogenesis, including pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), and fructose-1, 6-bisphosphatase (FBP). It also downregulates the transcriptional and protein levels of hepatocyte nuclear factor 4α (HNF4α) and cAMP response element binding protein (CREB), the two transcriptional factors involved in gluconeogenesis. Thus, ISL inhibits hepatic gluconeogenesis in T2DM mice. In addition, ISL reduces total cholesterol (TC) and triglyceride (TG) levels in the livers of T2DM mice. Moreover, ISL downregulates the mRNA levels of lipogenesis genes and upregulates those of genes involved in fatty acid oxidation, lipid uptake, and lipid export. In conclusion, ISL suppresses hepatic gluconeogenesis, promotes lipolysis, and restrains lipogenesis in T2DM mice, thereby improving the abnormal glycolipid metabolism caused by T2DM.

Immunological rejection is the major barrier to successful transplantation.The immune response to an allograft is an ongoing dialogue between the innate and adaptive immune system that will lead to the rejection of allograft.Activation of elements of the innate immune system,triggered as a consequence of tissue injury sustained during cell isolation or organ retrieval and ischemia reperfusion,will initiate and amplify the adaptive response.Identifying the molecular pathways that trigger tissue injury,signal transduction and rejection facilitates the identification of targets for the development of immunosuppressants.

Induction of immune tolerance is characterized by high efficiency,low toxicity and economic advantages,and immune tolerance has very important significance in organ transplantation.In the establishment of immune tolerance,dendritic cells (DCs) play the key roles such as clonal deletion or clonal anerge,expressing t-cell inhibiting factors,activating helper T cells electively and inducing regulatory T cells,especially CD4 + CD25 + regulatory T cells,etc.Similarly,CD4 + CD25 + regulatory T cells whose primary target point is dendritic cell also have various functions such as affecting dendritic cells'maturing,restraining dendritic cells'antigen presentation to T cells,inhibiting the activation of T cells in non-specific ways and inducing immune tolerance.Current research shows,dendritic cells and CD4 + CD25 + regulatory T cells regard each other as target point and work synergetically.Here we mainly discuss the function and interaction of dendritic cells and CD4 + CD25 + regulatory T cells in the immune tolerance.

Background: Radiation pneumonitis is one of the most common complications during radiotherapy of thoracic tumors. It impacts the quality of life of the patients and has life-threatening danger. However, there is a lack of drugs for prevention and treatment of this disease. Objective: To evaluate the efficacy of Liangxue Jiedu Huoxue Decoction, a compound traditional Chinese herbal medicine, in prevention of radiation pneumonitis. Design, setting, participants and interventions: A prospective randomized clinical study was conducted. A total of 100 patients diagnosed with lung cancer from Department of Radiotherapy, Chinese PLA General Hospital, who were planning to receive radiotherapy, were randomly assigned into treatment group and control group, with 50 patients in each group. In the treatment group 3 cases were lost to follow-up and one case was excluded, while in the control group 6 cases were lost to follow-up and 2 cases were excluded. Patients in the treatment group were treated with Liangxue Jiedu Huoxue Decoction in addition to radiotherapy, while patients in the control group were treated with radiotherapy alone. Main outcome measures: The incidence rates of radiation pneumonitis in the two groups were calculated. Acute radiation injury scoring criteria by Radiation Therapy Oncology Group (RTOG), clinical-radiographic-physiologic (CRP) score system, and Karnofsky Performance Status Scale (KPS) were used to evaluate the status of the patients. Results: The incidence rate of radiation pneumonitis was lower in the treatment group than in the control group (13.04% versus 33.33%, P<0.05). According to the RTOG scale, the extent of lung injury was improved in the treatment group as compared with that in the control group (P<0.05). The CRP score in the treatment group was significantly lower than that in the control group (P<0.05). The KPS score in the treatment group was significantly higher than that in the control group (P<0.05). Conclusion: Liangxue Jiedu Huoxue Decoction can decrease the incidence rate of radiation pneumonitis, reduce the extent of the lung injury, alleviate the symptoms of radiation pneumonitis, and improve life quality of the patients.

Aortic Aneurysm ; diagnosis ; Aortic Aneurysm, Thoracic ; diagnosis ; Carotid Body Tumor ; diagnosis ; Diagnostic Errors ; Humans ; Male ; Middle Aged

Objective To study the effect of S-adenomethionine on early stage recovery of transplanted liver.Methods From January 2010 to October 2012,57 liver transplantation patients were divided into 2 groups beginning the first day:group A,23 patients were treated with routine liver-protecting therapy,including glycyrrhizin,glutathione,albumin; group B,34 patients treated with additional S-adenomethionine (Transmetil).AST,ALT,T-BIL,D-BIL,γ-GT,ALB and ALP were compared between the two groups at pre-operation and post-operation day 1,day 4,day 7 and day 14.Results All patients suffered from preoperative hyperbilirubinemia,decreased ALB and elevated concentration of AST,ALT,γ-GT and ALP.On the first day after transplant,AST,ALT,T-BIL,D-BIL and γ-GT elevated and ALB decreased significantly in all cases compared with that before operation (respectively t =10.493,7.089,6.584,15.134,5.164,10.344,5.289,13.034,3.389,4.366,all P ＜ 0.01).On the contrary,the value of ALB was lower (respectively t =8.239,11.662,all P ＜ 0.05).On the fourth day posttransplant,ALB level was higher and that of other parameters were lower in group B when compared with group A (respectively t =2.536,2.736,2.218,3.318,4.804,2.892,all P ＜ O.05).This tendency of liver function improvement continued till postoperative day 7 in all cases while the differences between the two groups remained significant (respectively t =6.107,3.256,2.929,11.688,8.964,2.857,all P ＜ 0.05)except for γ-GT.On day 14,while T-BIL and D-BIL in group B were lower than that in group A (respectively t =4.413,8.493,all P ＜0.001),differences of liver functions were not significant between the two groups (respectively t =1.916,1.414,1.168,1.035,1.604,all P ＞ 0.05).Conclusions Transmetil promotes the recovery of transplanted liver's function,elevates the concentrantion of ALB and reduces the concentration of AST,ALT,T-BIL,D-BIL,γ-GT and ALP at early stage after liver transplant.