Neuropsychology, as well as cognitive neuroscience investigates the process of human cognition using several in vivo systemic approaches in order to explore neural mechanism. Besides the routine clinical neuropsychological assessments, up to date the latest neuroimaging techniques based on acoustics, optics, electricity and magnetism, have been applied to construct three-dimensional neuroimaging representations through mathematic models, and to identify functional areas or lesions in the brain. Presently, the combined use of functional MRI (fMRI) and event related potential (ERP) techniques is pioneering, especially when integrated synchronously.

Sapacitabine is an orally bioavailable prodrug of the nucleoside analog 2'-C-cyano-2'-deoxy-1-β-D-arabino-pentofuranosylcytosine (CNDAC). Both the prodrug and active metabolite are in clinical trials for hematologic malignancies and/or solid tumors. CNDAC has a unique mechanism of action: after incorporation into DNA, it induces single-strand breaks (SSBs) that are converted into double-strand breaks (DSBs) when cells go through a second S phase. In our previous studies, we demonstrated that CNDAC-induced SSBs can be repaired by the transcription-coupled nucleotide excision repair pathway, whereas lethal DSBs are mainly repaired through homologous recombination. In the current work, we used clonogenic assays to compare the DNA damage repair mechanism of CNDAC with two other deoxycytidine analogs: cytarabine, which is used in hematologic malignacies, and gemcitabine, which shows activity in solid tumors. Deficiency in two Rad51 paralogs, Rad51D and XRCC3, greatly sensitized cells to CNDAC, but not to cytarabine or gemcitabine, indicating that homologous recombination is not a major mechanism for repairing damage caused by the latter two analogs. This study further suggests clinical activity and application of sapacitabine that is distinct from that of cytarabine or gemcitabine.
Animals ; Antimetabolites, Antineoplastic ; pharmacology ; Arabinonucleosides ; pharmacology ; CHO Cells ; Cricetinae ; Cricetulus ; Cytarabine ; analogs & derivatives ; pharmacology ; Cytosine ; analogs & derivatives ; pharmacology ; DNA Breaks, Double-Stranded ; drug effects ; DNA Repair ; drug effects ; DNA-Binding Proteins ; deficiency ; Deoxycytidine ; analogs & derivatives ; pharmacology ; Homologous Recombination ; genetics ; Inhibitory Concentration 50 ; Prodrugs

OBJECTIVETo investigate the effect of microRNA-205 reduction by antagomirs on adhesion ability of normal human corneal epithelial keratinocytes (NHCEKs).

METHODSAntagomir-205, complementary and inhibitory to microRNA-205, was used to suppress endogenous microRNA-205 in NHCEKs. The adhesion ability of treated NHCEKs was then assessed by cell adhesion assay. Immunoblot and immunohistochemistry were conducted to determine the level of two focal adhesion-related proteins, focal adhesion kinase (FAK) and paxillin (Pax). Phalloidin staining was performed to measure the level of filamentous actin in antagomir-treated NHCEKs.

RESULTSAntagomir-205 markedly reduced the level of microRNA-205 in NHCEKs and significantly enhanced adhesion ability of NHCEKs (P<0.01). Further protein analysis validated that inhibition of microRNA-205 increased the number of phosphorylated FAK and phosphorylated Pax, and decreased filamentous actin.

CONCLUSIONOur findings suggest that microRNA-205 has down-regulating effect on cell motility in NHCEKs.

Base Sequence ; Cell Adhesion ; genetics ; Cells, Cultured ; Epithelium, Corneal ; cytology ; Humans ; Keratinocytes ; cytology ; MicroRNAs ; antagonists & inhibitors ; Oligonucleotide Probes

OBJECTIVETo evaluate and select excellent germplasm resources of Artemisia annua L., providing basic data for data base and breeding of A. annua.

METHODSeventy-two germplasms of A. annua, which were collected from main production areas, were planted in germplasm resources garden in Jingxi and Nanning under the same conditions. The samples were gathered in the squaring stage. Artemisinin was extracted by supersonic wave and determined by ultraviolet spectrophotometry.

RESULTThe leaf's yield and the content of artemisinin in the samples of different germplasms were varied significantly. Effect of environment on artemisinin content was more than that of hereditary factors. The content of artemisinin was different when the same material of A. annua grew in different place. The content of artemisinin in next year's plant was decreasing.

CONCLUSIONSSeven germplasms from south of China have been selected, their content of artemisinin was above 0.9% and calculated yield was more than 2250 kg x hm(-2). The content of artemisinin has been affected by hereditary factors and variation of the growth environment.

Artemisia annua ; growth & development ; metabolism ; Artemisinins ; metabolism ; China

This study was aimed to explore whether the GVHD in mice can be ameliorated and the GVL effect in mice can be reserved by transfusion of lymphocytes of donors fed with recipient splenocytes effect. Male (DBA-2) mice (H-2(d)) as donors were fed with BALB/c splenocytes, DBA-2 splenocytes, bovine serum albumin, or regular chow, every other day. Induction of tolerance was assessed by a mixed lymphocyte reaction (MLR). Female (BALB/c) mice (H-2(d)) as recipients received total body irradiation (TBI) of 6.0 Gy ((60)Cogamma-ray) followed by inoculation of 3 x 10(3) P388 mouse leukemia cells on the same day. Subsequently, tail vein injection of 2 x 10(7) splenocytes supplied by DBA-2 was undertaken. Control groups were fed identically without leukemia cell inoculation. The results showed that GVHD was significantly ameliorated and CD4(+)/CD8(+) ratio increased in recipient-mice transplanted with splenocytes of tolerated donors, compared with control animals. There was no significant difference in survival rate between different groups of recipients inoculated with leukemia cell. It is concluded that the peroral recipient-mouse splenocytes can ameliorate GVHD without hampering effect on GVL.
Adjuvants, Immunologic ; pharmacology ; Animals ; Cell Extracts ; immunology ; pharmacology ; Cell Transplantation ; Female ; Graft vs Host Disease ; immunology ; prevention & control ; Graft vs Leukemia Effect ; immunology ; Leukemia P388 ; therapy ; Lymphocytes ; immunology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred DBA ; Spleen ; cytology ; immunology ; Whole-Body Irradiation

Reasonable sampling scheme is the important basis for establishing reliable population pharmacokinetic model. It is an effective method for estimation of population pharmacokinetic parameters with sparse data to perform population pharmacokinetic analysis using the nonlinear mixed-effects models. We designed the sampling scheme for amlodipine based on D-optimal sampling strategy and Bayesian estimation method. First, optimized sample scenarios were designed using WinPOPT software according to the aim, dosage regimen and visit schedule of the clinical study protocol, and the amlodipine population model reported by Rohatagi et al. Second, we created a NONMEM-formatted dataset (n = 400) for each sample scenario via Monte Carlo simulation. Third, the estimation of amlodipine pharmacokinetic parameters (clearance (CL/F), volume (V/F) and Ka) was based on the simulation results. All modeling and simulation exercises were conducted with NONMEM version 7.2. Finally, the accuracy and precision of the estimated parameters were evaluated using the mean prediction error (MPE) and the mean absolute error (MAPE), respectively. Among the 6 schemes, schemes 6 and 3 have good accuracy and precision. MPE is 0.1% for scheme 6 and -0.6% for scheme 3, respectively. MAPE is 0.7% for both schemes. There is no significant difference in MPE and MAPE of volume among them. Therefore, we select scheme 3 as the final sample scenario because it has good accuracy and precision and less sample points. This research aims to provide scientific and effective sampling scheme for population pharmacokinetic (PK) study of amlodipine in patients with renal impairment and hypertension, provide a scientific method for an optimum design in clinical population PK/PD (pharmacodynamics) research.
Adult ; Age Factors ; Alanine Transaminase ; blood ; Amlodipine ; pharmacokinetics ; pharmacology ; Antihypertensive Agents ; pharmacokinetics ; pharmacology ; Bayes Theorem ; Body Weight ; Calcium Channel Blockers ; pharmacokinetics ; pharmacology ; Humans ; Hypertension ; metabolism ; Metabolic Clearance Rate ; Middle Aged ; Models, Biological ; Monte Carlo Method ; Nonlinear Dynamics ; Renal Insufficiency ; metabolism ; Software

This study was aimed to investigate a new method of avoiding graft-vs-host disease (GVHD) through selective elimination of alloreactive donor lymphocytes by using total body irradiation (TBI) and cyclophosphamide (Cy). Female (BALB/c x C57BL/6) F1 mice (H-2(d/b)) as recipients received (60)Co gamma-ray sublethal TBI of 4 Gy on day 0 followed by being inoculated with P388D1 leukemia cell line on day 1, injection of allogeneic splenocytes from C57BL/6 male mice (H-2(b)) was carried out for induction of graft-vs-leukemia (GVL) effect prior to stem cell transplantation (SCT), intraperitoneally injection of cyclophosphamide (Cy) (200 mg/kg) and TBI (9 Gy) was given on day 6. One day later, treated mice were rescued with bone marrow hematopoietic stem cells from (BALB/c x C57BL/6) F1 male mice (H-2(d/b)). The results showed that recipients had no occurrence of leukemia and GVHD through selective elimination of alloreactive donor lymphocytes by Cy and TBI, survived more than 210 days, the complete-donor chimerism occurred on day 21 after transplantation. The ratio of chimerism descended subsequently, but still displayed mixed-chimerism at 90 days. Control mice died of GVHD, leukemia or other death-related-transplantation within 20 to 36 days (P<0.01). It is concluded that to induce GVL effects by MHC mismatched splenocytes given before syngeneic bone marrow transplantation followed by selective elimination of alloreactive donor lymphocytes through TBI and Cy, graft-vs-host disease was thus avoided.
Animals ; Cyclophosphamide ; therapeutic use ; Female ; Graft vs Host Disease ; prevention & control ; Graft vs Tumor Effect ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Leukemia P388 ; therapy ; Lymphocyte Depletion ; Lymphocytes ; immunology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Whole-Body Irradiation

Our previous studies have demonstrated that Fam20C promotes differentiation and mineralization of odontoblasts, ameloblasts, osteoblasts and osteocytes during tooth and bone development. Ablation of the Fam20C gene inhibits bone and tooth growth by increasing fibroblast growth factor 23 in serum and causing hypophosphatemia in conditional knockout mice. However, control and regulation of the expression of Fam20C are still unknown. In this study, we generated a transgenic reporter model which expresses green fluorescence protein (GFP) driven by the Fam20C promoter. Recombineering was used to insert a 16 kb fragment of the mouse Fam20C gene (containing the 15 kb promoter and 1.1 kb of exon 1) into a pBluescript SK vector with the topaz variant of GFP and a bovine growth hormone polyadenylation sequence. GFP expression was subsequently evaluated by histomorphometry on cryosections from E14 to adult mice. Fluorescence was evident in the bone and teeth as early as E17.5. The GFP signal was maintained stably in odontoblasts and osteoblasts until 4 weeks after birth. The expression of GFP was significantly reduced in teeth, alveolar bone and muscle by 8 weeks of age. We also observed colocalization of the GFP signal with the Fam20C antibody in postnatal 1- and 7-day-old animals. Successful generation of Fam20C-GFP transgenic mice will provide a unique model for studying Fam20C gene expression and the biological function of this gene during odontogenesis and osteogenesis.
Animals ; Calcium-Binding Proteins ; genetics ; Extracellular Matrix Proteins ; genetics ; Green Fluorescent Proteins ; genetics ; HEK293 Cells ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Odontogenesis ; genetics ; Osteogenesis ; genetics

Adult ; Beijing ; HIV Infections/diagnosis* ; HIV Testing ; Health Promotion ; Homosexuality, Male ; Humans ; Internet ; Male ; Self-Testing

The liver has a complex cellular composition and a remarkable regenerative capacity. The primary cell types in the liver are two parenchymal cell populations, hepatocytes and cholangiocytes, that perform most of the functions of the liver and that are helped through interactions with non-parenchymal cell types comprising stellate cells, endothelia and various hemopoietic cell populations. The regulation of the cells in the liver is mediated by an insoluble complex of proteins and carbohydrates, the extracellular matrix, working synergistically with soluble paracrine and systemic signals. In recent years, with the rapid development of genetic sequencing technologies, research on the liver's cellular composition and its regulatory mechanisms during various conditions has been extensively explored. Meanwhile breakthroughs in strategies for cell transplantation are enabling a future in which there can be a rescue of patients with end-stage liver diseases, offering potential solutions to the chronic shortage of livers and alternatives to liver transplantation. This review will focus on the cellular mechanisms of liver homeostasis and how to select ideal sources of cells to be transplanted to achieve liver regeneration and repair. Recent advances are summarized for promoting the treatment of end-stage liver diseases by forms of cell transplantation that now include grafting strategies.
Humans ; Liver/surgery* ; Hepatocytes/transplantation* ; Stem Cells/metabolism* ; Liver Diseases/surgery*