Cerebral infarction is not only a focal damage,but also causes secondary damage in areas remote from the ischemic territory,which will retard the recovery of neurological function.Ephrin receptor B2 (EphB2) plays an important role in the development and repair mechanism of central nervous system.Blocking the effect of EphB2 in brain by using a specific inhibitor may enhance proliferation and migration of endogeneous neuronal stem cells after experimental cerebral infarc- tion,improve neurological function and influence angiogenesis and neuroplasticity in remote sites.It is expected to become a new approach for decreasing damages in areas remote from the cerebral infarction and promoting the recovery of neurological function.

Animals ; Animals, Newborn ; Drugs, Chinese Herbal ; therapeutic use ; Excitatory Amino Acid Antagonists ; therapeutic use ; Hypoxia-Ischemia, Brain ; metabolism ; prevention & control ; Memantine ; therapeutic use ; Platelet Activating Factor ; analysis ; Rats ; Rats, Sprague-Dawley

Purpose Brain complications severely threaten the treatment and survival of children with leukemia. This paper aims to investigate the MRI manifestations and differences of brain complications in leukemia before and after chemotherapy for a clinical guidance.Materials and Methods The clinical data and MRI findings of 37 children with leukemia and brain complications were retrospectively analyzed. Thirty-four of them underwent MRI scan twice or more, among whom 28 received contrast-enhanced MRI scan.Results Twenty-two patients were discovered with brain complications before chemotherapy, 2 of whom were with two kinds of complications. Meningopathy was found in 7 patients who showed widespread or localized meningeal thickening. Among them, 5 patients'' lesions reduced or disappeared after chemotherapy. Intracerebral multiple small and micro bleed was found in these 7 patients, 2 of them combined with hematoma. Three patients were found with intracranial tumor which all proved to be temporal bone tumor, 1 of whom combined with temporal lobe tumor and 1 had tumor disappeared after chemotherapy. The other complications before chemotherapy included leukoencephalopathy (n=2), subdural collection of fluid (n=2), meninges and parenchymal infiltration of leukemia (n=1), fungal infection (n=1) and cerebral infarction (n=1). On the contrary, 17 patients were discovered with brain complications after chemotherapy, 8 of whom were with two or more complications. Two patients had different kinds of complications before and after chemotherapy. Brain atrophy was observed in 13 patients. Leukoenphalopathy was found in 9 patients who presented high signal in white matter of double periventricular and/or semi-oval center on T2WI; the lesions of 4 patients were reduced or disappeared after withdrawal. Infectious diseases were diagnosed in 3 patients, including viral encephalitis in 2 cases, tuberculous meningitis combined with tuberculoma in 1 case. The other complications included intracranial tumor (n=2), sinus thrombosis (n=1), posterior reversible encephalopathy syndrome (n=1) after chemotherapy. Conclusion The MRI findings of brain complications in childhood leukemia are various and demonstrate significantly different features before and after chemotherapy. The major complications before treatment include meningopathy and intra-cerebral hemorrhage;while after chemotherapy the main complications are brain atrophy, leukoencephalopathy and infectious diseases. MRI proves to be a valuable method to detect, observe and follow up these complications.

Objective To assess the feasibility of a novel 99Tcm labelled polypeptide analogue for interleukin-11 receptor ( IL11R) imaging in a bone metastases model for prostate cancer. Methods A novel circular polypeptide analogue of IL11 ( c( CGRRAGGSC ) ) was indirectly labeled with 99Tcm and the product was named as 99Tcm-DTPA-IL11 RR. The labeling efficiency, radiochemical purity and stability of the product were measured with paper chromatography and high performance liquid chromatography (HPLC). The biodistribution of 99Tcm-DTPA-IL11RR was investigated in 28 ICR normal mice. The organ radioactivity was measured as percentage activity of injection dose per gram of tissue ( %ID/g). The models of bone metastases from prostate cancer were established at the tibias of BALB/c nude mice bearing human prostate cancer PC-3 cells. The tumor bearing ( n= 5 ) and standard closed fracture nude mice models underwent both 99Tcm-DTPA-IL11RR and 99Tcm-methylene diphosphonate (MDP) scintigraphy study. The images were acquired at 0.5, 1,2, 4, 6, 8, 24 h after intravenous injection of the tracers. The competitive inhibition imaging was perfomed in three tumor bearing mice. One-way variance analysis was used. Results The labeling efficiency was 90.7%. The radiochemical purity of 99Tcm-DTPA-IL11RR in normal saline solution was (99.57 ±0.09)%, (99.29 ±0.18)%, (98.95 ±0.78)%, (98.67 ±0.11)%, (96.53 ±0.91)%, (95.20±0.70)%, (88.38 ±0.22)% and (36.17±1.29)% at room temperature after0, 1,2, 3, 4, 6, 8 and 24 h, respectively. The tracer radiochemical purity in the blood of ICR mice remained over 90% at 37 C for 6 h. The labeling compounds were excreted mainly through kidney. The peak uptake of bone ( ( 1.910 ±0.109) %ID/g) and liver ( (0.366 ±0.030) %ID/g) was at 4 h after injection. In the tumor bearing mice, the uptake of spine marrow and large joints of extremities was mild. The highest uptake at tumor region was at 4 h and persistent at 6-8 h after injection. The tumor to non-tumor ratios (T/NT) were 1.17 ±0.17, 2.20 ±0.29, 3.20 ±0.15, 3.67 ±0.23, 13.61±0.85, 9.45 ±0.37 and 3.33 ±0.30 at 0.5,1, 2, 4, 6, 8 and 24 h, respectively (F=621.54, P＜0.05). In the standard closed fracture models,high uptake of 99Tcm-MDP was shown at the fracture site, with no increased 99Tcm-DTPA-IL11RR uptake noted. The tumor uptake was significantly depressed after a pre-injection of the unlabeled polypeptide analogue. Conclusions The synthesis of 99Tcm-DTPA-IL11RR is stable and the labeling efficiency is high. It may be a potential molecular probe in metastatic bone imaging for prostate cancer.

Traditional herbal medicines, Panax ginseng, Panax quinquefolium and Panax notoginseng, attract our attention for their extensive and powerful pharmacological activities. Ginsenosides are the main active constituents of these medicinal herbs. The related glycosyltransferases involved in ginsenoside biosynthesis are the key enzymes which catalyze the last important step. Modification of ginsenoside aglycones by glycosyltransferases produces the complexity and diversity of ginsenosides, which have more extensive pharmacological activity. At present, ginsenoside aglycones and compound K have been obtained by synthetic biology. As the last step of ginsenoside biosynthesis, glycosylation of ginsenoside aglycones has been studied intensively in recent years. This review summarizes the basic strategies and research advances in studies on glycosyltransferases involved in ginsenoside biosynthesis, which is expected to lay the theoretical foundation for the in-depth research of biosynthetic pathway of ginsenosides and their production by synthetic biology.
Biosynthetic Pathways ; Ginsenosides ; biosynthesis ; Glycosyltransferases ; metabolism ; Panax ; chemistry ; Plants, Medicinal ; chemistry ; Synthetic Biology

AIM: To observe the inhibition of c-Met inhibitor on proliferation of lens epithelial cells (LECs).METHODS: Human's LECs were cultured and hepatocyte growth factor (HGF) and K252a were added to second passage of cells supplied with Dulbecco's modified eagle's medium (DMEM). MTT assay was used to examine the proliferation of LECs, and Western-blot was used to detect the expression change of Bcl-2 and Caspase-3.RESULTS: The photodensity (A) of HGF (50nmol/L) + K252a (30nmol/L) was not significantly different from that of DMEM control (P＞0.05). The expression of Bcl-2 and Caspase-3 were not significantly different from that in the control group.CONCLUSION: K252a, the inhibitor of c-Met, can effectively inhibit the proliferation of LECs.

Objective To evaluate the pattern of energy metabolism and nutrients intake in patients with chronic viral hepatitis and posthepatitic cirrhosis to effectively direct their nutrition therapy.Methods Resting energy expenditure (REE) was measured with open-circuit indirect Jorimetry in 60 patients with chronic viral hepatitis and 60 patients with posthepatitic cirrhosis.Their normal basal energy expenditure (BEE) was predicted by Harris-Benedict equation and energy intake (EI) was determined by diet recall. Correlation between REE and indicators for nutrition assessment was analyzed.Results REE was (77? 21) kJ?kg~(-1)?d~(-1) in 60 patients with pusthepatitic cirrhosis,significantly lower than BEE[(95?16) kJ? kg~(-1)?d~(-1)(P0.05,and their EI was (127?34) kJ?kg~(-1)?d~(-1),1.41?0.43 times as REE,in which PROI was (1.02?0.29) g?kg~(-1)?d~(-1),1.31?0.61 times as PROE (0.87?0.34) g?kg~(-1)?d~(-1),also indicating a negative nitrogen balance (-2.02?4.07).REE,EI and intake of three nutrients,serum level of albumin and prealbumin (PA) and body weight significantly decreased in patients with posthepatitic cirrhosis,as compared to those in patients with chronic viral hepatitis (P

The cyclization of 2,3-oxidosqualene is the key branch point of ergosterol and triterpenoid biosynthesis. Downregulation of 2,3-oxidosqualene metabolic flux to ergosterol in Saccharomyces cerevisiae may redirect the metabolic flux toward the triterpenoid synthetic pathway. In our study, primers were designed according to erg7 gene sequence of S. cerevisiae. Three fragments including 5' long fragment, 5' short fragment and erg7 coding region fragment were amplified by PCR. 5' long fragment consists of the promoter and a part of erg7 coding region sequence. 5' short fragment consists of a part of promoter and a part of erg7 coding region sequence. These fragments were inserted reversely into pESC-URA to construct antisense expression plasmids. The recombinant plasmids were transformed into S. cerevisiae INVSc1 and recombinant strains were screened on the nutritional deficient medium SD-URA. The erg7 expression level of recombinant strains, which harbored antisense expression plasmid of erg7 coding region, was similar to that of INVScl by semi-quantitative PCR detection. But erg7 expression level of recombinant strains, which harbored 5' long antisense fragment and 5' short antisense fragment, was significantly lower than that of the control. The results of TLC and HPLC showed that the ergosterol content of recombinant strains, which harbored 5' long antisense fragment, decreased obviously. The ergosterol contents of the others were almost equal to that of INVSc1. Lanosterol synthase gene expression was downregulated by antisense RNA technology in S. cerevisiae, which lays a foundation for reconstructing triterpenoid metabolic pathway in S. cerevisiae by synthetic biology technology.
DNA Primers ; Down-Regulation ; Gene Expression ; Intramolecular Transferases ; genetics ; metabolism ; Plasmids ; Polymerase Chain Reaction ; RNA, Antisense ; Saccharomyces cerevisiae ; enzymology ; genetics ; Squalene ; analogs & derivatives ; metabolism ; Transformation, Genetic

Pichia pastoris is one of the most important systems used in the field of molecular biology for the expression of recombinant proteins. The system has advantages of high expression, high stability, high secretion, easy high-density fermentation and low cost. Many factors affect the expression of recombinant protein, such as gene copy number, codon usage preference, type of promoter, molecular chaperones, glycosylation, signal peptide and fermentation process. In this review, research advances of the above aspects are summarized, which lay a foundation for improving the expression of recombinant proteins in P. pastoris.
Fermentation ; Gene Dosage ; Glycosylation ; Molecular Chaperones ; Pichia ; metabolism ; Promoter Regions, Genetic ; Protein Sorting Signals ; Recombinant Proteins ; biosynthesis

OBJECTIVETo investigate the effects of serotonin (5-HTIA) receptors in the hippocampal dentate gyrus (DG) on active avoidance learning in rats.

METHODSTotally 36 SD rats were randomly divided into control group, antagonist group and agonist group(n = 12). Active avoidance learning ability of rats was assessed by the shuttle box. The extracellular concentrations of 5-HT in the DG during active avoidance conditioned reflex were measured by microdialysis and high performance liquid chromatography (HPLC) techniques. Then the antagonist (WAY-100635) or agonist (8-OH-DPAT) of the 5-HT1A receptors were microinjected into the DG region, and the active avoidance learning was measured.

RESULTS(1) During the active avoidance learning, the concentration of 5-HT in the hippocampal DG was significantly increased in the extinction but not establishment in the conditioned reflex, which reached 164.90% ± 26.07% (P <0.05) of basal level. (2) The microinjection of WAY-100635 (an antagonist of 5-HT1A receptor) into the DG did not significantly affect the active avoidance learning. (3) The microinjection of 8-OH-DPAT(an agonist of 5-HT1A receptor) into the DG significantly facilitated the establishment process and inhibited the extinction process during active avoidance conditioned reflex.

CONCLUSIONThe data suggest that activation of 5-HT1A receptors in hipocampal DG may facilitate active avoidance learning and memory in rats.

8-Hydroxy-2-(di-n-propylamino)tetralin ; pharmacology ; Animals ; Avoidance Learning ; Dentate Gyrus ; physiology ; Piperazines ; pharmacology ; Pyridines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptor, Serotonin, 5-HT1A ; physiology ; Serotonin ; physiology ; Serotonin Receptor Agonists ; pharmacology