Novel radioligands for imaging sigma-1 receptor in brain using positron emission tomography (PET)

The sigma-1 receptor (R) is a unique intracellular protein. R plays a major role in various pathological conditions in the central nervous system (CNS), implicated in several neuropsychiatric disorders. Imaging of R in the brain using positron emission tomography (PET) could serve as a noninvasively tool for enhancing the understanding of the disease's pathophysiology. Moreover, R PET tracers can be used for target validation and quantification in diagnosis. Herein, we describe the radiosynthesis, PET/CT imaging of novel R C-labeled radioligands based on 6-hydroxypyridazinone, [C]HCC0923 and [C]HCC0929. Two radioligands have high affinities to R, with good selectivity. In mice PET/CT imaging, both radioligands showed appropriate kinetics and distributions. Additionally, the specific interactions of two radioligands were reduced by compounds and (self-blocking). Of the two, [C]HCC0929 was further investigated in positive ligands blocking studies, using classic R agonist SA 4503 and R antagonist PD 144418. Both R ligands could extensively decreased the uptake of [C]HCC0929 in mice brain. Besides, the biodistribution of major brain regions and organs of mice were determined . These studies demonstrated that two radioligands, especially [C]HCC0929, possessed ideal imaging properties and might be valuable tools for non-invasive quantification of R in brain.

Analysis on the gene mutations of MYOC in primary open angle glaucoma pedigree / 中华检验医学杂志

Objective To screen the mutations of MYOC gene in a Chinese primary open angle glaucoma (POAG) family from Cbengqing and investigate the relationship between the mutations in MYOC/TIGR gene and POAG.Methods In a large 4-generation glaucoma family, myocilin gene (MYOC) was screened in 39 family members, 8 of which were confirmed patients. Normal controls included 100 normal Chinese subjects.The known mutations of MYOC gene ( including G34C, C136T, G144T, G227A, C624G,G736A, C1009G, A1036G, C1081T, G1099A, G1138A, A1139C, T1430A, C1441A and C1442T) were detected by single strand conformation polymorphism(SSCP) , po]ymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis and DNA sequencing.Results G227A mutation was detected in 2 POAG patients and 1 asymptomatic patient, but not in the controls.Cl009del mutation was identified in all patients of the pedigree and an offspring member but not in the controls. No other mutations were detected.Since the C1009del mutation was revealed for the first time, a new GenBank number FJ237047 correponding to ACI62293 was applied.Conclusions The G227A mutation is a known site and there is no relationship between G227A mutation and glaucoma. But C1009del may be related to glaucoma which suggests that morbidity could be higher in the relatives of POAG than the controls.

Relationship between gene polymorphism of serum amyloid A protein 1 and coronary heart disease / 临床检验杂志

Objective To research the relationship between the gene polymorphism of serum amyloid A protein(SAA)1 and coronary heart disease(CHD).Methods By using PCR-RFLP and sequencing,the gene polymorphism of SAA1 of 183 patients with coronary heart disease and 152 healthy controls were analyzed.Result In the both groups 3 alleles(1.1,1.3,1.5)and 6 genotypes(1.1/1.1,1.1/1.5,1.1/1.3,1.3/1.3,1.3/1.5 and 1.5/1.5)were found.The frequency of 1.5 allele in healthy controls group was notably higher than that in CHD group(P

Advances in research on Survivin ,the inhibitor of apoptosis in cancer diagnosis and therapy / 中国癌症杂志

WTBZ]Survivin belongs to the member of IAP family (inhibitor of apoptosis, IAP) proteins and is a bifunctional protein that suppresses apoptosis and regulates cell division. Survivin is a tumor specific antiapoptosis factor that is expressed selectively in all the most common human carcinomas but not in normal adult tissues. Studies indicated that Survivin played a crucial role in the genesis and progression of malignancy and was an important predictive/prognostic parameter in tumors. Survivin also participates in angiogenesis. Recently, Survivin has been used as a novel diagnostic/therapeutic target in cancer.

Protective effects of sodium ferulate on the PC12 cells apoptosis induced by H_2O_2 / 中国药理学通报

AIM To study the mechanism of the protective effects of sodium ferulate (SF) on apoptosis of PC12 cells induced by Hydrogen peroxide(H 2O 2). METHODS Based on the model of apoptosis of PC12 cells induced by H 2O 2, cell viability was tested by MTT assay. The expressions of mRNA and protein were tested by RT-PCR and Western blot. RESULTS Pretreatment with different concentrations of SF (25～250 ?mol?L -1) for 1h increased the survival rate of PC12 cells, decreased the expressions of par-4, caspase-3 mRNA and Par-4 protein, while there was no obvious change of the activity fregment of caspase-3 P20 and caspase-3 activity. CONCLUSION SF can prevent the PC12 cells against H 2O 2 neurotoxicity in a concentration-dependent fashion. The mechanism of protection is likely related to decreasing the Par-4 level, and the relation with Caspase-3 needs further study.