Adult ; Brain Diseases ; chemically induced ; Ethylene Dichlorides ; poisoning ; Female ; Humans ; Male ; Middle Aged ; Occupational Diseases ; chemically induced

Asialoglycoprotein receptor (ASGPR) is highly expressed on the surface of parenchymal liver cells. It can specifically recognize and bind to desialylated glycoproteins which contain terminal galactose or N-acetylgalactosamine residues, and endocytosed by clathrin-mediated endocytosis, transported and then degraded in lysosome. Based on this character, ASGPR mediated liver-targeted drug delivery is likely to increase drug distribution, reduce potential side effects and lower dose. This article reviewed the expression, structure, ligand binding and endocytosis of ASGPR, and summarized the design and optimization of ASGPR ligands and the release strategies. Finally, we put forward some expects about the clinical drug development for ASGPR.

Pathological cardiac hypertrophy is a maladaptive response in a variety of organic heart disease(OHD),which is characterized by mitochondrial dysfunction that results from disturbed energy metabolism. SIRT3, a mitochondria-localized sirtuin, regulates global mitochondrial lysine acetylation and preserves mitochondrial function. However, the mechanisms by which SIRT3 regulates cardiac hypertrophy remains to be further elucidated. In this study, we firstly demonstrated that expression of SIRT3 was decreased in AngiotensionⅡ(AngⅡ)-treated cardiomyocytes and in hearts of AngⅡ-induced cardiac hypertrophic mice. In addition, SIRT3 overexpression protected myocytes from hypertrophy, whereas SIRT3 silencing exacerbated Ang II-induced cardiomyocyte hypertrophy.In particular,SIRT3-KO mice exhibited significant cardiac hypertrophy. Mechanistically, we identified NMNAT3 (nicotinamide mononucleotide adenylyltransferase 3), the rate-limiting enzyme for mitochondrial NAD biosynthesis, as a new target and binding partner of SIRT3.Specifically,SIRT3 physically interacts with and deacety-lates NMNAT3,thereby enhancing the enzyme activity of NMNAT3 and contributing to SIRT3-mediated anti-hypertrophic effects.Moreover,NMNAT3 regulates the activity of SIRT3 via synthesis of mitochon-dria NAD.Taken together,these findings provide mechanistic insights into the negative regulatory role of SIRT3 in cardiac hypertrophy.Sirtuin 3(SIRT3),a mitochondrial deacetylase that may play an impor-tant role in regulating cardiac function and a potential target for CHF

DNA microarrays have been acknowledged to represent a promising approach for the detection of viral pathogens. However, the probes designed for current arrays could cover only part of the given viral variants, that could result in false-negative or ambiguous data. If all the variants are to be covered, the requirement for more probes would render much higher spot density and thus higher cost of the arrays. Here we have developed a new strategy for oligonucleotide probe design. Using type I human immunodeficiency virus (HIV-1) tat gene as an example, we designed the array probes and validated the optimized parameters in silico. Results show that the oligo number is significantly reduced comparing with the existing methods, while specificity and hybridization efficiency remain intact. The adoption of this method in reducing the oligo numbers could increase the detection capacity for DNA microarrays, and would significantly lower the manufacturing cost for making array chips.

OBJECTIVETo study the chemical constituents of the dried roots of Zanthoxylum dimorphophyllumr. spinifolium and to find out the active constituents of the plant.

METHODModern chromatography was used to purify chemical constituents, and their structures were identified by various spectral methods.

RESULTFour compounds were isolated and identified as isopimpinellin (I), xanthoxyletin (II), 6-(2', 3'-dihydroxy-3'-methyl-butyl)-7-hydroxy-2H-1-benzopyran-2-one (III), 6-(2'-O-beta-D-glucopyranosyloxy, 3'-dihydroxy-3'-methybutyl)-7-hydroxy-2H-1-benzopyran-2-one (IV).

CONCLUSIONAll of the above compounds were isolated from the above mentioned plant for the first time.

Coumarins ; chemistry ; isolation & purification ; Furocoumarins ; chemistry ; isolation & purification ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Zanthoxylum ; chemistry

OBJECTIVE: To determine the mechanism of peritoneal fibrosis of peritoneal mesothelial cells by high glucose. METHODS: The third passage human peritoneal mesothelial cells (HPMCs) from primary culture were divided into a control group (F(12)) and high glucose groups (F(12)+4% glucose) in different times (24, 48 h). The cell proliferation was assayed by the method of MTT (methylthiazoletetrazolium). The cell damage was measured by LDH (lactate dehydrogenase). The protein expression of fibronectin (FN), transforming growth factor-beta1(TGF-beta(1)) and connective tissue growth factor (CTGF) were detected by ELISA. The mRNA expression of FN, TGF-beta(1) and PAI-1 were detected by RT-PCR. RESULTS: High glucose suppressed the cell proliferation. The result of MTT showed that compared with the control group, the value of OD of high glucose groups at 24 or 48 h decreased significantly (P<0.01 or 0.01); The cell damage was enhanced in high glucose groups, at 24 or 48 h compared with the control group at the same time (all P<0.01). The protein expressions of TGF-beta(1), CTGF and FN in supernate fluid of cell culture were significantly enhanced when high glucose stimulated the HPMCs in the high glucose groups at 24 or 48 h compared with the control group at the same time (P<0.05 or 0.001). The expressions of FN, TGF-beta(1) and PAI-1 mRNA were upregulated in 24 h high glucose group compared with that of 24 h control group. CONCLUSION High glucose can suppress the HPMC proliferation and damage HPMCs. Increase of TGF-beta(1), CTGF, FN and PAI-1 of HPMCs stimulated by high glucose can promote the synthesis and decreased degradation of extracellular matrix, which might be related with the mechanism of peritoneal fibrosis of peritoneal mesothelial cells by high glucose.
Cell Proliferation ; drug effects ; Cells, Cultured ; Epithelial Cells ; metabolism ; pathology ; Fibronectins ; biosynthesis ; genetics ; Glucose ; pharmacology ; Humans ; Peritoneal Dialysis ; Peritoneum ; metabolism ; pathology ; Plasminogen Activator Inhibitor 1 ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Transforming Growth Factor beta ; biosynthesis ; genetics

Objective:This study was to investigate the expression of long noncoding RNA (lncRNA) KCNQ1OT1 during the differentiation program of human preadipocyte and to look for the changes of its expression in adipose tissue in obese subject, as well as to clarify the correlation between KCNQ1OT1 and obesity, and to provide clues for further understanding the role of lncRNA in the development of obesity.Methods:Quantitative PCR was used to detect the expression of KCNQ1OT1 in human preadipocyte at day 0, 1, 3, 5, 9, and 12 during differentiation program, quantitative PCR was also used to detect KCNQ1OT1 expression in white adipose tissue of obese and normal people, which related to PPIA internal reference gene. Pearson correlation analyses were used to explore the relationships of KCNQ1OT1 with body mass index, triglyceride, and total cholesterol.Results:During differentiation program, the relative expression of KCNQ1OT1 levels at day of 1, 3, 5, 9, and 12 were (25.89±3.10), (24.78±5.58), (15.53±2.11), (6.75±0.71), (4.81±0.84), which showed an upward trend compared with day 0. This difference was significant ( P<0.01), especially in the early stage of differentiation (day 1 and day 3). The relative expression of KCNQ1OT1 in visceral adipose tissue of obese subjects was 0.79±0.05, which was significantly higher than that of normal people ( P<0.01). KCNQ1OT1 was positively correlated with body mass index ( r=0.569, P<0.01), triacylglycerol content ( r=0.489, P<0.05), and total cholesterol content( r=0.591, P<0.01). Conclusion:KCNQ1OT1 expression level, which was up-regulated in adipose tissue from obese subjects, increased during the differentiation program of preadipocytes, and also positively correlated with body mass index and serum triglyceride content. These results suggest that KCNQ1OT1 may be an important regulator of human preadipocyte differentiation and a potential target for prevention and treatment of obesity.

OBJECTIVETo evaluate the clinical outcome of reconstruction of maxillary defects with vascularized iliac crest flap and simultaneous osseointegrated implant embedding.

METHODSDuring September to October 2003, two patients with maxillary defects from tumor resection underwent microsurgical reconstruction. The free iliac osteomuscular flap transferring and simultaneous osseointegrated implant embedding were performed to repair the defects. Three months after the reconstructive surgery, an abutment operation was preformed and denture was applied in both cases.

RESULTSThe flaps survived well. Postoperative follow-up for 8 to 9 months showed that the patients obtained good zygomaxillary appearance, normal occlusion, and satisfactory pronunciation, without oronasal fistula or other serious complications.

CONCLUSIONSThe free iliac crest osteomuscular flap with simultaneous osseointegrated implant embedding is an ideal, effective and cosmetically acceptable method for maxilla reconstruction.

Adult ; Bone Transplantation ; methods ; Female ; Humans ; Ilium ; transplantation ; Male ; Maxilla ; surgery ; Middle Aged ; Transplantation, Homologous ; Treatment Outcome

The total RNA was extracted from peripheral blood mononuclear cells (PBMC) which was isolated from Meishan porcine and induced with concanavaline A (ConA), then the porcine interferon gamma gene (PoIFNgamma, 501bp) was amplified by RT-PCR. The result of sequencing demonstrated that the amplified PoIFNgamma had 100% nucleotide homology with the other porcine IFNgamma sequence published on GenBank. The objective gene (PoIFNgamma) was inserted into adenoviral shuttle vector, pShuttle-CMV, to construct recombinant plasmid pSh-PoIFNgamma. And it was co-electrotransformated with adenoviral skeletal vector pAdEasy-1 into competent cells of BJ5183. The transforms were cultured at 37 degrees C for 24h on kanamycin resistance plate and selected for smaller colonies. Then, the extracted recombinant plasmid was named pAd-Sh-PoIFNgamma, which was confirmed by Pac I digestion, and transformed into XL10-Glod(r) for copious preparation. pAd-Sh-PoIFNgamma linearized with Pac I was co-transfected with liposome into 293 package cell-line. After 7d-10d, the typical cytopathic effect indicated that recombinant adenoviral genome (deleted with E1 and E3 genes) carrying PoIFNgamma was successfully packaged into intact virion. The recombinant virion was successively seeded to the 10th generation and the viral genome was extracted from each generation by PCR. The antiviral activity of PoIFNgamma was tested by CPE50 method. The results showed that the PoIFNgamma expressed by adenovirus had high antiviral activity, which was 1.3 x 10(6) U/mL against VSV in MDBK cells. The results demonstrated that the recombinant adenovirus carrying PoIFNgamma could be stably passaged.
Adenoviridae ; genetics ; Animals ; Antiviral Agents ; pharmacology ; Interferon-gamma ; genetics ; pharmacology ; Recombinant Proteins ; biosynthesis ; pharmacology ; Swine

BACKGROUNDXS0601, consisting of active ingredients (Chuangxiongol and paeoniflorin), has been shown to inhibit arterial neointimal hyperplasia in animal models and in preliminary human studies. The objective of this study was to evaluate the safety and efficacy of XS0601 in preventing restenosis following percutaneous coronary intervention (PCI).

METHODSA multi-center, randomized, double-blind, placebo-controlled trial was conducted. A total of 335 patients were randomized into treatment with the oral administration of XS0601, or a placebo for 6 months after successful PCI. Angiographic follow-up was scheduled at 6 months, and clinical follow-ups performed at 1, 3 and 6 months after PCI. The primary end point was angiographic restenosis. The secondary end points were the combined incidence of death, target lesion nonfatal myocardial infarction, repeat angioplasty, and coronary artery bypass graft surgery.

RESULTSA total of 308 patients (91.9%) completed the study and 145 cases (47.1%) received angiographic follow-up. The restenosis rates were significantly reduced in the XS0601 group as compared with the placebo group (26.0% vs. 47.2%, P < 0.05), and the minimum lumen diameter (MLD) was greater [(2.08 +/- 0.89) mm for XS0601 vs. (1.73 +/- 0.94) mm for placebo, P < 0.05]. XS0601 also significantly reduced the combined incidence of major adverse cardiac event (10.4% in the XS0601 group vs. 22.7% in the placebo group, P < 0.05). The incidence of recurrent angina at 3 and 6 months after PCI was also significantly reduced in XS0601 group (7.1% and 11.0%) as compared with those in placebo group (19.5% and 42.9%) (P < 0.05). No significant side effects occurred within the 6-month follow-up period in the XS0601 group.

CONCLUSIONAdministration of XS0601 for 6 months is demonstrated to be safe and effective in reducing restenosis in post-PCI patients.

Adult ; Aged ; Angina Pectoris ; prevention & control ; Angioplasty, Balloon, Coronary ; Coronary Restenosis ; epidemiology ; prevention & control ; Double-Blind Method ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Prospective Studies ; Stents