Objective To study effect and its possible mechanism of total glucosides of paeony ( TGP ) on adriamycin-induced nephropathy rats.Methods Thirty male SD rats were randomly divided into normal group ( CON) , adriamycin-induced nephropathy group ( ADRN) and TGP-treated ADRN group (TGP).The rat nephropathy model was established by adriamycin injection.At the end of the 8th week after treatment, ELISA was used to detect the level of Cr and BUN.The values of 24 urine protein was determined by urinary protein kit.Masson staining was used to observe the fibrosis.RT-PCR was used to detect the mRNA levels of TLR4/NF-κB/TGF-β1 .Immunohistochemical method was used to detect the content of TLR4/NF-κB/TGF-β1.ResuIts Compared with the CON group, the level of Cr, BUN, 24 urine protein of ADRN group rised(P<0.01), the degree of fibrosis of ADRN group were aggravated(P<0.01), and the expressions of TLR4/NF-κB/TGF-β1 of ADRN group increased significantly.However, compared with ADRN group, the(P<0.01) level of Cr, BUN, 24 urine protein of TGP-treated rats reduced(P<0.01), the degree of fibrosis of TGP-treated rats eased(P<0.05), and the expressions of TLR4/NF-κB/TGF-β1 of TGP-treated rats decreased significantly.ConcIusion TGP retards the process of fibrosis and reduces the pathological damage in adriamycin-induced rats by down-regulating the expression of TLR4/NF-κB/TGF-β1 signaling.

Objective To establish the quality standard for Chanhou Zhuyu Capsules.Methods Leonurus Japonicus and Ligusticum chuanxiong in Chanhou Zhuyu Capsules were identified by TLC,and the content of stachydrine hydrochloride was determined by TLC Scanning.Results The quality identification by TLC was specific.Stachydrine hydrochloride had a good linearity in the range of 4.0～12.0 ?g,r=0.999 7,and the average recovery was 99.87 %,RSD=1.67 %.Conclusion The methods of identification and content determination are simple,reliable and reproducible.They can be used effectively for the quality control of Chanhou Zhuyu Capsules.

Nitrites play multiple characteristic functions in invasion and metastasis of hepatic cancer cells, but the exact mechanism is not yet known. Cancer cells can maintain the malignant characteristics via clearance of excess mitochondria by mitophagy. The purpose of this article was to determine the roles of nitrite, reactive oxygen species (ROS) and hypoxia inducing factor 1 alpha (HIF-1 α) in mitophagy of hepatic cancer cells. After exposure of human hepatocellular carcinoma SMMC-7721 cells to a serial concentrations of sodium nitrite for 24 h under normal oxygen, the maximal cell vitality was increased by 16 mg x (-1) sodium nitrite. In addition, the potentials of migration and invasion for SMMC-7721 cells were increased significantly at the same time. Furthermore, sodium nitrite exposure displayed an increase of stress fibers, lamellipodum and perinuclear mitochondrial distribution by cell staining with Actin-Tracker Green and Mito-Tracker Red, which was reversed by N-acetylcysteine (NAC, a reactive oxygen scavenger). DCFH-DA staining with fluorescent microscopy showed that the intracellular level of ROS concentration was increased by the sodium nitrite treatment. LC3 immunostaining and Western blot results showed that sodium nitrite enhanced cell autophagy flux. Under the transmission electron microscopy (TEM), more autolysosomes formed after sodium nitrite treatment and NAC could prevent autophagosome degradation. RT-PCR results indicated that the expression levels of COX I and COXIV mRNA were decreased significantly after sodium nitrite treatment. Meanwhile, laser scanning confocal microscopy showed that sodium nitrite significantly reduced mitochondrial mass detected by Mito-Tracker Green staining. The expression levels of HIF-1α, Beclin-1 and Bnip3 (mitophagy marker molecular) increased remarkably after sodium nitrite treatment, which were reversed by NAC. Our results demonstrated that sodium nitrite (16 mg x L(-1)) increased the potentials of invasion and migration of hepatic cancer SMMC-7721 cells through induction of ROS and HIF-1α mediated mitophagy.

Pharmacometrics,developed from the conventional pharmacokinetics,is the science of applying mathe-matical and statistical methods to characterize,understand,and predict a drug's pharmacokinetic,phannacodyna-mic,and biomarker-outcome behaviors.Pharmacometrics has been widely valued for its utility of modeling and simulation in drug research and development,therapeutic drug monitoring and individualized therapy.This paper reviewed the advances of pharmacometrics employed in new drug research and development and therapeutic drug monitoring both at home and abroad.

Animals ; Cannabinoid Receptor Antagonists ; therapeutic use ; Cannabinoids ; pharmacology ; Fibrosis ; metabolism ; Humans ; Liver Cirrhosis ; etiology ; metabolism ; therapy ; Piperidines ; therapeutic use ; Pyrazoles ; therapeutic use ; Receptor, Cannabinoid, CB1 ; metabolism ; Receptor, Cannabinoid, CB2 ; metabolism ; Receptors, Cannabinoid ; metabolism ; Scleroderma, Diffuse ; metabolism ; Signal Transduction ; drug effects ; Skin ; metabolism ; Smad Proteins ; metabolism ; Transforming Growth Factor beta1 ; metabolism

Objective To investigate the influence of Wharton's jelly (W J) transplant on brain inflammation and mood status in traumatic brain injury (TBI) mouse model.Methods The WJ was isolated from human umbilical cord and cultured,and the cell phenotype of P3 human umbilical cord mesenchymal stem cells was identified by flow cytometry.The animal model was established by modified weight drop method.Experimental mice were randomly(random number) divided into Veh(normal saline)and WJ transplantation groups.After 3 days,water content of damaged brain was detected.Elisa kit was used to detect the expression of IL-1β and TNF-αt.The expression of GFAP,Ibal and CD68 were detected by immunofluorescence.Het(hydroethidine) staining was used to detect reactive oxygen species (ROS) production.Neurologic deficit score was used to evaluate the motor function,sucrose preference test,tail suspension test and forced swim test were used to detect the depression of mice.The data were expressed in ((-x)±s) and analysed by SPSS 21.0 software.Two-way ANOVA with repeated measures design was used to compare difference bewteen two groups at multiple interval.Results Compared with Veh group,the mice in the WJ group had a better performance in NDS scored test(d 1:14.8± 1.169 vs.15.2+ 1.472);3d:(11.0±1.414 vs.13.5+1.225);7d:(9.5±1.517 vs.12.0±1.549);14d:(7.7±0.816 vs.10.5±1.643);21d:(6.5±0.547 vs.9.0±1.265);28d:(5.3+0.816 vs.7.8±1.169),P＜0.05].After TBI,WJ tissue transplantation increased sucrose preference index from (54.49±1.505)％ to (64.56±2.279)％ (P=0.004),decreased immobility time using tail suspension test from (144.7±5.493)s to (115.7±4.660)s (P＜0.01),and decreased immobility time using forced swim test from (260.3±4.558)s to (215.8±5.003)s (P=0.002).After WJ transplantation,brain water content was reduced from (84.48±1.802)％ to (75.58+1.559)％ (P=0.004),the expression of IL-1β and TNF-α near injury area also decreased(P=0.000 6 and 0.000 3),as well as the expression of ROS(P=0.020).The fluorescence intensity of activated astrocytes decreased from (2 906±431.591)to (165 8±312.912) (P=0.041),and the number of microglias and activated microglias were both reduced(P=0.049 and P＜0.01) after TBI.Conclusions Wharton's jelly alleviated the inflammation and depression in traumatic brain injured mice.

BACKGROUND:The production and release of a large amount of inflammatory factors caused by immune system inflammatory response mainly contributes to secondary spinal cord injury. OBJECTIVE:To investigate the effects of umbilical cord Wharton’s jely mesenchymal stem cel transplantation on repair of injured neurological function and expression of inflammatory factors monocyte chemoattractant protein 1 and interleukin 10 in rats with acute spinal cord injury. METHODS: Eighty-one healthy adult male Sprague-Dawley rats were randomly and equaly divided into sham operation, model and cel transplantation groups, with 27 rats per group. Rats in the latter two groups were subjected to hemisection of the spinal cord to establish acute spinal cord injury models. Rat models in the cel transplantation group received umbilical cord Wharton’s jely mesenchymal stem cel injection (1×106)via the tail vein. Rat neurological function was evaluated using the BBB score at different time points after spinal cord injury. The expression of monocyte chemoattractant protein 1 and interleukin 10 in injured spinal cord tissue was detected using ELISA assay at different time points after spinal cord injury. Migration and neuronal differentiation of umbilical cord Wharton’s jely mesenchymal stem cels in the injured spinal cord tissue were determined using immunohistochemical staining method. RESULTS AND CONCLUSION:Compared with the sham operation and model groups, rat neurological function was significantly recovered in the cel transplantation group (P < 0.05). Compared to the model group, monocyte chemoattractant protein 1 level in the serum and monocyte chemoattractant protein 1 mRNA and protein expression in the injured spinal cord tissue were significantly lower (P < 0.05), but interleukin 10 mRNA and protein expression in the injured spinal cord tissue was significantly higher (P < 0.05), in the cel transplantation group. In the cel transplantation group, umbilical cord Wharton’s jely mesenchymal stem cels could migrate to the injured region and express glial fibrilary acidic protein. These findings suggest that umbilical cord Wharton’s jely mesenchymal stem cels promote rat neurological function recovery by regulating the inflammatory response in the injured spinal cord tissue, which is likely to be one of mechanisms by which transplantation of umbilical cord Wharton’s jely mesenchymal stem cels treats spinal cord injury.

BACKGROUND: In recent years, with the progress of shock therapy as well as the establishment and promoted application of arterial bypass grafting, thrombolytic therapy, percutaneous transluminal coronary angioplasty, extracorporeal circulation on cardiac surgery, cardiopulmonary resuscitation, limb replantation, and organ transplantation, blood reperfusion in multiple organs after ischemia has been achieved. However, the organs which undergo a period of ischemia appear to have the performance of damage aggravation.OBJECTIVE: To summarize the research progress of MG53 protein in protecting five organs from ischemia/reperfusion injury, thereby providing reference for further in-depth study.METHODS: A computer-based online search of PubMed, Duxiu Knowledge Search and CNKI databases was performed for relevant literatures puldished between 1986 and 2016. The key words were MG53, TRIM, Mitsugumin53, ischemic, reperfusion, preconditioning, postconditioning, RISK, membrane damage, Connexin43, KChIP2 in English and MG53, ischemia/reperfusion in Chinese. Finally 61 eligible articles were reviewed in accordance with the inclusion and exclusion criteria. RESULTS AND CONCLUSION: As a muscle-specific TRIM family protein, endogenous MG53 is involved in the repair of muscle cytomembrane damage, and the protective effects of ischemic preconditioning and postconditioning. Exogenous recombinant human MG 53 protein not only repairs membrane damage of various muscles and non-muscle cells, but also protects the myocardium, skeletal muscle, brain, lung and kidney from ischemia/reperfusion injury.

Objective To induce human umbilical cord mesenchymal stem cells (hUC-MSCs) to hair-cell like cells in the inner ear, using a two-step neural differentiation method.Methods The hUC-MSCs were obtained from human umbilical cords by tissue adherence culture,whose surface antigen CD29, CD34, CD44, CD45, CD90, HLA-ABC, and HLA-DR could be identified by flow cytometry.In the neural stem cells induced phase, the NSE positive cells were analyzed by microscope and immunohistochemistry.In the second stage, the expression of hair-cell like cells markers (Math1, MyosinⅦa, Brn3c) were tested by qRT-PCR and immunofluorescence method.Results The control group and the protocol group had little NSE after differentiation while the protocol B group presented a neurobiological structure and demonstrated a higher NSE positive ratio after 5 days' neural stem cells induction (P<0.05).Compared to the control group, the mRNA and protein level of Math1, MyosinⅦa, and Brn3c exhibited a significant increase in the differential group,which induced for 4 weeks in the hair-cell like cells in the inner ear's induced phase(P<0.05).Conclusion The two-stage induction (hUC-MSCs-neural stem cells-hair-cell like cells) could produce more MyosinⅦa,Brn3c and Math1,which may provide an appropriate way to treat sensorineural deafness.

Taurine-upregulated gene 1 (TUG1) is a recently identified oncogenic long non-coding RNA (lncRNA),that is overexpressed in various digestive system tumor tissues and cell lines,including esophageal cancer,gastric cancer,liver cancer,cholangiocarcinoma and biliary tract cancer,pancreatic cancer and colorectal cancer.Studies have shown that TUG1 participates in tumor cells proliferation,apoptosis,migration and invasion,and high expression of TUG1 is associated with clinicopathological features and prognosis of cancer patients,suggesting that lncRNA TUG1 is likely represents a feasible biomarker or therapeutic target in human digestive system cancers.