Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor on hypoxia responses in mammalian tissues. HIF-1 plays as a positive factor in solid tumor and leads to hypoxia-driven responses that enhance its downstream gene expression for tumor growth and survival. LXY6099 was obtained by the structural modification and optimization of manassantin A (MA) as a high potent HIF-1 inhibitor. Antitumor activity of LXY6099 was observed in this study. LXY6099 with an IC50 value of 2.46 x 10(-10) mol x L(-1) showed more sensitive inhibition activity to HIF-1 than that of MA detected by reporter gene assay (> 100 folds). It showed strong inhibition on the growth of human solid tumor cell lines. Furthermore, LXY6099 exhibited significant antitumor activity against established human tumor xenografts in nu/nu mice with treatment of MX-1 breast cancer. Thus, LXY6099 as a novel HIF-1 inhibitor could be further developed into anti-cancer agents.
Animals ; Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; metabolism ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Heterografts ; Humans ; Hypoxia-Inducible Factor 1 ; metabolism ; Lignans ; pharmacology ; Mice, Nude

Three-dimensional structure model of azoreductase AZR of Rhodobacter sphaeroides was con- structed using homology modeling method. It is a flavodoxin adopting ?/? structure. Structure alignment of two different types of flavin-dependent azoreductases revealed that they possessed high similarity. Based on sequence and structure analysis, site-directed mutagenesis of K109H and K109A were performed. The opti- mal pH values are pH 6 and pH 9 for K109H and K109A mutant protein, respectively. The optimal tempera- ture (30℃) is not affected by mutagenesis. Positively charged residues at position 109 is necessary for the binding of methyl red, while K109H is not a conserved mutagenesis for the binding of NADPH. K109 may only be involved in the binding of the 2’-phosphate group of NADPH and have no effect on the binding of NADH.

Objective To discuss methods of decoration reconstruction for finger defect in emergency and to observe the elinical effects.Methods Of the 41 cases of finger injuries of different degrees,15 were repaired with part of the skin flaps of the big toenails or skin flaps of the second toenalis,8 were repaired with part of the skin flaps of the big toenails,7 were reeonstructed with the second tiptoes,11 were repaired with the abdominal skin flaps of the big toes or lateral flaps of the second toes.Results All the 41 fingers sur- vived.One skin flap of the big toe was somewhat swelling and a decorating operation was performed.The 4～18 months of follow-up visitation of the rest cases revealed good function and shapes.No obvious functional ab- norality was found in the donating feet.Conclusion Various kinds of decoration reeonstruetion for finger defects are available to recover the hand shape and function as much as possible.

OBJECTIVE: To elucidate the correlation between CKLF-like marvel transmembrane domain containing member (CMTM5) gene and the risk of in-stent restenosis (ISR) with coronary artery disease (CAD) patients and to detect the effects and mechanisms of CMTM5-stimulated genes on human vascular endothelial cells (ECs) proliferation and migration. METHODS: A total of 124 hospitalized patients in Shijitan Hospital were enrolled in this study. All the CAD patients were detected with platelet reactivity and grouped into two groups according to platelet reactivity; ISR was conformed by coronary angiography; RT-PCR method was used to detect CMTM5 gene expression; The CMTM5 over expression, reduction and control EC lines were established; Cell count, MTT, Brdu and flow cytometry methods were used to detect the proliferation of ECs, scratch and transwell experiments to test the migration of ECs, Western blot was used to detect signal path expressions. RESULTS: CMTM5 gene expression in HAPR (High on aspirin platelet reactivity) group was 1.72 times compared with No-HAPR group, which was significantly higher than No-HAPR group. HAPR group ISR rate was 25.8% (8 cases), the incidence of No-HAPR ISR group was 9.7% (9 cases), and the results showed that in HAPR group, the incidence of ISR was significantly higher than that in No-HAPR group (P=0.04, OR=0.04, 95%CI=1.16－7.52), which showed that CMTM5 gene was significantly correlated with the risk of ISR. In HAPR group ISR rate was 25.8% (8 cases), the incidence of ISR in No-HAPR group was 9.7% (9 cases), and the results showed that the risk of ISR in HAPR group was significantly higher than that in No-HAPR group. All the results showed that CMTM5 was significantly correlated with the risk of ISR in CAD patients (P < 0.05). CMTM5 overexpression inhibited the proliferation and migration ability of ECs (P < 0.05), PI3K/Akt signaling pathways were involved in the role of regulation on ECs. CONCLUSION Our results revealed that CMTM5 gene was closely related with ISR, CMTM5 overexpression may repress ECs proliferation and migration through regulating PI3K-Akt signaling.
Chemokines ; Coronary Artery Disease/surgery* ; Coronary Restenosis ; Drug-Eluting Stents/adverse effects* ; Endothelial Cells ; Humans ; MARVEL Domain-Containing Proteins ; Phosphatidylinositol 3-Kinases ; Tumor Suppressor Proteins

OBJECTIVE: To elucidate the correlation between CKLF-like MARVEL transmembrane domain containing member 5 (CMTM5) gene and the risk of coronary artery disease (CAD), and to detect the effects of CMTM5 gene expression changes on the ability of adhesion and migration of THP-1 cells. METHODS: Using case-control method, a total of 700 hospitalized patients in Shijitan Hospital were enrolled in this study. CAD were diagnosed by coronary angiography, which was defined as at least one blood vessel diameter stenosis ≥50% according to the result of coronary angiography. Reverse transcription-polymerase chain reaction (RT-PCR) method was used to detect CMTM5 gene expression; enzyme linked immunosorbent assay (ELISA) method to detect the plasma level of CMTM5; and Logistic regression to analyze CMTM5 genes and the risk of CAD. Human vascular endothelial cells (ECs) and THP-1 cells were cultivated, adhesion and Transwells experiments were used to evaluate the chemotactic capabi-lity of CMTM5 gene on THP-1 cells. RESULTS: In this study, 350 CAD patients matched with 350 control patients were included. RT-PCR results revealed CMTM5 mRNA expression in CAD group was 3.45 times compared with control group, which was significantly higher than that in control group (P < 0.05). The levels of CMTM5 plasma protein in CAD group was (206.1±26.9) μg/L, which was significantly higher than that in control group (125.3±15.2) μg/L (P < 0.05). After adjusted for the risk factors of age, gender, BMI, smoking, hypertension, diabetes and hyperlipidemia, Logistic regression analysis results indicated that CMTM5 was the susceptibility factors of CAD, which still had significant correlation with CAD (P < 0.05). Adhesion and Transwells experiments results revealed that the numbers of adhesion and migration of THP-1 cells in CMTM5 overexpression ECs group (EO group) were significantly higher than that in lenti-mock infected ECs group (EO-MOCK group), non-infected ECs group (EN group), lenti-mock infected ECs group (ES-MOCK group), and CMTM5 suppression ECs group (ES group). On the contrary, the numbers of adhesion and migration of THP-1 cells in ES group were significantly lower than that in the other four groups (P < 0.01). CONCLUSION CMTM5 gene was closely related to the development of CAD. CMTM5 overexpression promoted the adhesion and migration of THP-1, which might play a part in the mechanisms of atherosclerosis and CAD.
Chemokines ; Coronary Angiography ; Coronary Artery Disease/genetics* ; Endothelial Cells ; Humans ; MARVEL Domain-Containing Proteins ; Tumor Suppressor Proteins

OBJECTIVETo study the protective effects and the possible mechanism of shengmai for injection(SM) against the experimental acute cardiogenic shock.

METHODThe experimental acute cardiogenic shock model was established by ligating the anterior descending cornonary in dogs. The effects of SM on cardiogenic shock were investigated by measuring the hemodynamics parameter, the activity of LDH, CK, SOD and the contents of MDA in blood serum.

RESULTIn the dogs treated with SM, the mean arterial pressure (MAP), heart rate (HR), left ventricular pressure (LVP), the maximum of its first derivative (+/- dp/dtmax), the cardiac output (CO) and the cardiac index (CI) were increased significantly. The left ventricular end diastolic pressure (LVEDP) and the peripheral vascular resistance (TPVR) were decreased significantly, the myocardial infarct size was redused observely. In addition, the activity of LDH, CK and the contents of MDA in serum were decreased significantly, however the activity of SOD was increased observely.

CONCLUSIONThe results indicate that SM has the protective effects on cardiogenic shock.

Animals ; Cardiac Output ; drug effects ; Cardiotonic Agents ; administration & dosage ; pharmacology ; therapeutic use ; Creatine Kinase ; blood ; Dogs ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Female ; Heart Rate ; drug effects ; Hemodynamics ; drug effects ; physiology ; Injections, Intravenous ; L-Lactate Dehydrogenase ; blood ; Male ; Malondialdehyde ; blood ; Myocardial Infarction ; pathology ; prevention & control ; Ophiopogon ; chemistry ; Panax ; chemistry ; Phytotherapy ; Plants, Medicinal ; chemistry ; Random Allocation ; Schisandra ; chemistry ; Shock, Cardiogenic ; blood ; physiopathology ; prevention & control ; Vascular Resistance ; drug effects

OBJECTIVETo explore the effect of Yanghe Huayan Decoction (YHD, a representative recipe for warming yang mass dissipating) in inhibiting precancerosis of breast cancer (PBC) and on the protein and mRNA expression of ki67.

METHODSThe PBC rat model was established by dimethylbenzanthracene (DMBA), and 9 weeks later rats were randomly divided into the blank control group, the model group, the YHD group, the Sanjie Huatan Decoction group (SHD), the Pingxiao Tablet group (PT), and the tamoxifen group. Rats in the model group were administered with water by gastrogavage. Rats in the YHD group received YHD (deglued antler powder 12 g, prepared rhizome of rehmannia 9 g, cassia bark 6 g, white mustard seed 3 g, zedoary root 12 g, appendiculate cremastra pseudobulb 15 g, chekiang fritillary bulb 9 g, licorice root 6 g) at the daily dose of 7.2 g/kg by gastrogavage. Rats in the SHD group received SHD (oldenlandia diffusa 15 g, Scutellaria Barbata 15 g, Trichosanthes Kirilowii 15 g, pinellia 9 g) at the daily dose of 5.4 g/kg by gastrogavage. Rats in the PT group received PT at the daily dose of 144 mg/kg by gastrogavage. Those in the tamoxifen group received tamoxifen at the daily dose of 4 mg/kg by gastrogavage. Pathomorphological changes of the breast tissue were observed by HE staining. The positive rate and the gray value of ki67 expression were detected by immunohistochemical assay. And the expression of ki67 mRNA was detected by q-PCR.

RESULTSCompared with the model group, the general hyperplasia and the occurrence rate of precancerous lesion were higher and the occurrence rate of invasive carcinoma was lower in each treatment group (P < 0.05). Except the SHD group, the intensity of ki67 grey value increased in each treatment group (P < 0.05, P < 0.01). Except the PT group, the positive rate of ki67 and mRNA expression of ki67 increased in the rest treatment groups (P < 0.05, P < 0.01). Compared with the YHD group, there was no statistical difference in the occurrence rate of infiltration or the occurrence rate of precancerous lesion (P > 0.05). The positive rate of ki67 expression and mRNA expression of ki67 increased in the PT group, showing statistical difference (P < 0.05).

CONCLUSIONSYHD could partially inhibit and reverse canceration of breast cancer. It also could inhibit ki67 protein and mRNA expression. Its effect was similar to tamoxifen and superior to PT. So it was suitable for prevention and treatment of precancerous lesion of breast cancer.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Ki-67 Antigen ; metabolism ; Mammary Neoplasms, Experimental ; chemically induced ; drug therapy ; metabolism ; Precancerous Conditions ; drug therapy ; metabolism ; Rats ; Rats, Sprague-Dawley

Adult ; Dermatitis, Occupational ; etiology ; Drug Eruptions ; etiology ; Humans ; Male ; Phthalimides ; adverse effects

The complete genomic sequence of Duck hepatitis virus 1 (DHV-1) ZJ-V isolate was sequenced and determined to be 7 691 nucleotides (nt) in length with a 5'-terminal un-translated region (UTR) of 626 nt and a 3'-terminal UTR of 315 nt (not including the poly(A) tail). One large open reading frame (ORF) was found within the genome (nt 627 to 7 373) coding for a polypeptide of 2 249amino acids. Our data also showed that the poly (A) tail of DHV-1 has at least 22 A's. Sequence comparison revealed significant homology (from 91.9% to 95.7%) between the protein sequences of the virus in the Picornaviridae family, its genome showed some unique characteristics. DHV-1 contains 3copies of the 2A gene and only 1 copy of the 3B gene, and its 3'-NCR is longer than those of other picornaviruses. Phylogenetic analysis to do sequence homology based on the VP1 protein sequences showed that the ZJ-V isolate shares high sequence homology with the reported DHV-1 isolates (from 92.9% to 99.2%), indicating that DHV-1 is genetically stable.

Abstract: Objective　To investigate the drug demand and related influencing factors of AIDS non-occupational post-exposure prophylaxis (nPEP) among men who have sex with men (MSM) in Wuhan, and to provide a scientific basis for the development of subsequent intervention policies for MSM. Methods　With the assistance of social organizations in Wuhan, MSM was recruited by the snowball method to carry out an online questionnaire survey to collect information on demographics, AIDS-related knowledge, high-risk behaviors, and the need for nPEP medication. The χ2 test and unconditional Logistic regression were used to analyze the related factors of the demand for nPEP medication. Results　A total of 308 valid subjects were included in this study, with predominantly 18-29 years old (78.57%, 242/308). The self-reported sexual orientation was mainly homosexuality (82.47%, 254/308), and the awareness rate of AIDS knowledge was high (89.29%, 275/308). Among the survey respondents, 35.06% (108/308) did not know the situation of HIV infection among MSM population in Wuhan; 55.19% (170/308) had two or more same-sex sexual partners in the last six months; 90.91% (280/308) had heard of nPEP before participating in this survey. After passing nPEP and informing the protective effect of nPEP, 59.42% (183/308) of them needed nPEP. After HIV exposure, 73.38% (226/308) were willing to spend money to buy nPEP drugs, and 88.64% (273/308) were willing to take nPEP drugs because of the known side effects. Logistic regression analysis showed that in the last six months, the needs for taking nPEP medication in those who had 2 or more same-sex sexual partners (OR=2.121, 95%CI: 1.329-3.386) and who had received peer education (OR=1.740, 95%CI: 1.088-2.781) were higher than those of those who had a same-sex sexual partner in the last six months and who had not received peer education. Conclusions　The MSM population in Wuhan has a great demand for nPEP drugs, and peer education is an important way to carry out nPEP publicity and promotion. At the same time, we should continue to strengthen warning publicity and education and behavioral intervention to reduce MSM risky sexual behaviors and reduce new HIV infections.