The MLN64 gene,which is localized in q12-q21 of the human chromosome 17,encodes a novel transmembrane protein containing 445 amino acids .The C-terminus of MLN64 shares significant homology with the steroidogenic acute regulatory (StAR)protein,while its N-terminal domain exhibits a function of targe-ting the protein to late endosomes .MLN64 is likely to be involved in cholesterol transport and synthesis of steroid hormones.MLN64 gene,coamplified with C -erbB-2,is overexpressed in certain breast carcinomas and exerts an influence on biological characteristics of breast cancer cells .The high levels of MLN 64 observed in some breast carcinomas could contribute to the growth and progression of these tumors through increased intratumoral steroido -genesis,and is considered as a predictive factor of breast cancer prognosis .

Objective To investigate therapeutic effect and molecular mechanism of RPS on Diabetic Nephropathy rats.Methods DN rats were induced by STZ injection and grouped into model group, low-dose RPS group, middle-dose RPS group, high-dose RPS group, Rosiglitazone group and normal group.24 h urine protein,kidney weight index,blood glucose level and TG, BUN and Scr level in normal and DN rats were detected.TGF-βlevel of serum of rats in all groups by ELISA were detected.mRNA and protein expression level of PPARγ,aP2 and GLUT4 by RT PCR and Western blot were also detected.Results DN rats were induced successfully because the 24 h urine protein, kidney weight index and the levels of blood sugar and TG, BUN,Scr l and TGF-βevels, and the mRNA level of PPARγ,aP2 and GLUT4 level in DN rats increased than normal group(P<0.05).The mRNA level of PPARγ,aP2 and GLUT4 level increased(P<0.05) and other indexes decreased(P<0.05) as the doses of RPS increasing.The therapeutic effects of Rosiglitazone group was better than high dose PRS group.The protein level of PPARγ, aP2 and GLUT4 in DN rat skeletal muscle were significantly lower than normal group(P<0.05), and RPS can increase their expression level obviously.Conclusion RPS has a dose-dependent therapeutic effect on DN rats by improving the expression level of related protein in PPAR gamma signaling pathways.

Aim To determine whether there existed melatonin receptor (MR) in adult hepatoma tissue and to observe its property of binding.Methods Immuno-histochemistry was used to detect MR and identify its subcellular distribution. Specific binding and kinetic analyses of melatonin receptor were measured by radioligand binding assay.Results The results of immunohistochemistry showed that MT1 and MT2 existed in membrane, cytosol and nucleus of the hepatoma cells, but the expression of them principally localized in the membrane and cytosol. The specific binding assay properties of MR were presented as follows: the maximum binding capacity (B_(max)) was (0.29±0.07) pmol·g~(-1) protein. Equilibrium dissociation constant (K_d) was (48.7±6.5) pmol·L~(-1). The trait of MR, saturation and reversibility, was detected by ~(125)I-Mel specific binding kinetic analyses.Conclusions MR exists in adult hepatoma cells, furthermore, the subtypes of MR (MT1 and MT2) coexist in the membrane and cytosol, respectively,whose characters of the specific binding sites were low binding capacity,high affinity,saturation and reversibility.

Animals ; Biogenic Monoamines ; metabolism ; Brain ; drug effects ; metabolism ; Female ; Lipid Peroxidation ; drug effects ; Male ; Mice ; Paraquat ; toxicity

Objective To investigate the value of pro-adrenomedullin (pro-ADM) levels for severity as-sessment of community-acquired pneumonia (CAP).Methods 214 CAP patients who were admitted to the emer-gency department were prospectively studied.The levels of plasma pro-ADM were determined using a new sandwich immunoassay.At the same time, procalcitonin, C-reactive protein, interleukin-6 levels, leukocyte count, clinical varia-bles and the pneumonia severity index (PSI) were measured.Results Pro-ADM levels,in contrast to procalcitonin,interleukin-6 levels, increased with increasing of the severity of CAP, which was classified according to the PSI score (P<0.05).In patients who died during follow-up, pro-ADM levels on admission were significantly higher than that in survivors [2.08 vs.4.94 μg/L,Z=-4.081 ,P<0.001].In a receiver operating characteristic (ROC) analysis for survival, the area under the ROC curve (AUC) for pro-ADM was 0.79, which was significantly higher than that for procalcitonin(0.72), C-reactive protein (0.58), interleukin-6 (0.64 ), and total leukocyte count (0.50) and sim-ilar to the AUC of the PSI (0.75).Conclusion Pro-ADM is a useful biomarker for the risk stratification of CAP patients.

Humans ; Medicine, Chinese Traditional ; Stomach Neoplasms ; therapy

Objective To explore effects and mechanism of inactivation of vitamin D receptor (VDR) in intestinal tumor growth of APCmin/+ mice. Methods To generate APCmin/+VDR -/- mice through breeding, the number and size of small intestinal and colonic tumors were assessed and compared between APCmin/+ and APCmin/+ VDR -/- mice. The intestinal tumors were diagnosed with HE stain. The expressions of BCL-2,vimentin-1,Stat-1 and MSH-2 proteins of tumors were determined by immanohistocbemistry and compared be-tween APCmin/+ and APCmin/+VDR -/- mice. Results A comparison between APCmin/+ and APCmin/+ VDR -/- mice revealed that the number of the tumors, which were larger than 3mm, was significantly increased in APCmin/+ VDR -/- mice at 4 months of age (P< 0.01). HE staining indicated fistulous adenomas from small intestine and colon of two groups, Immunostaining showed Stat - 1 level in APC-min/+ tumors were increased and MSH-2 and vimentin-1 levels in APCmin/+ VDR-/- mice were increased, compared to APCmin/+tumors. Conclusion These observations suggested that inactivation of VDR promoted the intestinal tumor growth of APCmin/+ mice.

Blood Pressure ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Hypertension ; drug therapy ; Inflammation

Cerebellum connects with each part of the auditory pathway directly or indirectly, forming the anatomical basis for a cerebellar role in auditory process. Functional imaging studies and clinical observations provide more abundant support for this view. Tinnitus is one of the most common clinical manifestations when the auditory system is impaired and remains unsolved. Basic science researches in neurotransmitter chemistry and molecular biochemistry, together with functional imaging studies, indicate that cerebellum might contribute to the pathophysiology of tinnitus. In this review we summarize the current understanding of cerebellar role in auditory process and tinnitus.
Auditory Pathways ; Cerebellum ; physiopathology ; Humans ; Tinnitus ; physiopathology

Objective:To clarify the effects of the BMP receptor inhibitor LDN-193189 in the dedifferentiated chondrosarcoma (DDCS) cell line NDCS-1 and to explore the anti-tumor mechanism of LDN-193189 in DDCS. Methods:NDCS-1 was treated with 5 nmol/L of LDN-193189. MTT assay and clone formation experiments were used to verify that LDN-193189 suppressed cel proliferation. Transwel and wound healing tests were performed to demonstrate that LDN-193189 inhibited cell invasion. Western blot detection was used to show that LDN-193189 inhibited the suppression of BMPR2, p-Smad1/5, and RUNX2 protein expression. Results:The BMPR2 signaling pathway was inhibited by LDN-193189;thus, cell viability and invasion were significantly suppressed. Conclusion:LDN-193189 induces the inhibition of progression in vitro via the BMPR2-p-Smad1/5-RUNX2 signaling pathway in the human DDCS cell line NDCS-1.