Antidiuretic Hormone Receptor Antagonists ; Heart Failure ; drug therapy ; Humans

An Aspergillus sp. strain F3 was isolated and identified from the rhizosphere soil of mangrove plant, Rhizophora stylosa Griff in Dongzhai harbor mangrove forest conservation in China. In this study, the effects of media salinity and pH on the mycelial biomass and the ability of producing antibacterial metabo- lites from this isolate were carefully analyzed. Results showed that this isolate can grow well on the SDA medium with higher salinity (3%~9%) and higher pH (8~10). Under the modified culturing conditions, this isolate can secret the antibacterial and antitumor metabolites. The extracts of acetic ether were about 448 mg/L of the fermentation broth. The antibacterial activities of the acetic ether extract were analyzed with bacteria and fungus. Results showed this extract can suppress the growth of Staphylococcus aureus、S. epi-dermidis、Sarcina lutea、Bacillus subtilis and Escherichia coli with MIC of 31.3 ?g/mL, 31.3 ?g/mL, 7.8 ?g/mL, 7.8 ?g/mL and 125.0 ?g/mL, respectively. It can also suppress the growth of Candida albicans with MIC of 125.0 ?g/mL. Further studies uncovered the cytotoxicity of this extract against the tumor cells, such as ECV304, Lovo and HepG2 with IC50 of 3.45 ?g/mL, 4.88 ?g/mL and 14.31 ?g/mL respectively.

Background and purpose:Chemotherapy plays an important role in the treatment of breast carcinoma by inhibiting the tumor growth and inducing the apoptosis.MAPK transduction pathway is closely related to proliferation and apoptosis of varieties of tumor cells,inhibition of MAPK pathway may increase the efficiency and decrease the toxicity of chemotherapy.Our study was to investigate the effect of MEK inhibitor PD98059 in response of breast cancer cell lines to Epirubicin.Methods:Human breast cancer cell lines MCF-7 and MCF-7/ADR were used as cell models.Epirubicin(EADM),PD98059(inhibitor of MAPK Kinase-MEK),or EADM+PD98059 was added into the culture medium,the expression of MEK2 and p-ERK were measured by Western blot,the growth of the two cell lines were measured by MTT.Results:ERK activity was elevated in MCF-7 after the treatment of EADM,the cells were more sensitive to EADM if combined with PD98059,while in MCF-7/ADR,ERK activity kept unchanged after EADM treatment,and PD98059 has no effect on the sensitivity of cells to EADM.Conclusion:MAPK signal transduction may be activated in some cells treated by EADM,adding inhibitor of MAPK signal transduction could improve the sensitivity of the cells to EADM.

Protein tyrosine phosphatase (PTP) 1B is a potential target for the treatment of diabetes and obesity. We have previously identified the benzoyl sulfathiazole derivative II as a non-competitive PTP1B inhibitor with in vivo insulin sensitizing effects. Preliminary SAR study on this compound series has been carried out herein, and thirteen new compounds have been designed and synthesized. Among them, compound 10 exhibited potent inhibition against human recombinant PTP1B with the IC50 value of 3.97 micromol x L(-1), and is comparable to that of compound II.
Humans ; Protein Tyrosine Phosphatase, Non-Receptor Type 1 ; antagonists & inhibitors ; Structure-Activity Relationship ; Sulfathiazoles ; chemistry ; pharmacology

OBJECTIVETo study the effect of puerarin on angiotensin II type 1 receptor (AT1) and angiotensin-converting enzyme 2 (ACE2) in spontaneous hypertension rat (SHR).

METHODSSHRs, 12 weeks old, were randomly divided into four groups: the model control group (A), the Verapamil group (B), and the two puerarin groups (C and D) treated by low dose and high dose of puerarin respectively. After being treated for 3 weeks, total RNA from tissues of heart, aorta and kidney in rats were extracted and mRNA expression levels of AT1 and ACE2 were determined by RT-PCR.

RESULTSAs compared with Group A, the mRNA expressions of AT1 and ACE2 in heart tissue were lower in Group C, and those in kidney tissue were higher in Group D (all P < 0.05); ACE2 mRNA expression was higher in Group D than in Group C (P < 0.05); no significant differences of the two indexes in aorta were shown among various groups. Besides, mRNA expressions of AT1 and ACE2 in heart and kidney tissue were proved to be positively linearly correlated.

CONCLUSIONHigh dose puerarin could increase the mRNA expressions of AT1 and ACE2 in kidney, while low dose puerarin could decrease them in heart; there might be a feed back correlation between AT1 and ACE2.

Animals ; Disease Models, Animal ; Gene Expression ; drug effects ; Heart ; drug effects ; Humans ; Hypertension ; drug therapy ; genetics ; metabolism ; Isoflavones ; administration & dosage ; Kidney ; drug effects ; metabolism ; Male ; Myocardium ; metabolism ; Peptidyl-Dipeptidase A ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Inbred Dahl ; Receptor, Angiotensin, Type 1 ; genetics ; metabolism

Adenocarcinoma ; diagnosis ; pathology ; Carcinoma, Squamous Cell ; diagnosis ; pathology ; Cervical Intraepithelial Neoplasia ; diagnosis ; pathology ; Female ; Humans ; Precancerous Conditions ; diagnosis ; pathology ; Retrospective Studies ; Uterine Cervical Neoplasms ; diagnosis ; pathology ; Vaginal Smears ; methods

With deeper understanding of gastrointestinal stromal tumor(GIST), more and more patients are diagnosed as GIST. Although the prognosis of early GIST is satisfactory after complete surgical resection, there are still many problems in the treatment of advanced GIST. Variety of treatment options has been used in the treatment of GIST, such as surgery, targeted drug therapy, and surgery plus imatinib therapy. However, post-operative recurrence, imatinib-resistance, multi-targeted drug resistance are still challenges. Many clinical evidences show that a reasonable management strategy can improve the prognosis of patients with advanced GIST. All the doctors should have a clear mind to carry out appropriate interventions. Advanced GIST should not be simply considered to be either medical or surgical disease, but rather must be systematically managed by multidisciplinary team approach combining surgical oncology, medical oncology, pathology, and interventional medicine. This review will advocate suitable treatment strategies based on the most recent progresses in systemic treatment for advanced GIST and our clinical experience to achieve early detection, early prevention, proper management, and therefore improve the survival of these patients.
Gastrointestinal Stromal Tumors ; diagnosis ; drug therapy ; pathology ; surgery ; Humans ; Neoplasm Metastasis

ObjectiveThe procedure of peroral endoscopic myotomy (POEM) was practiced in porcine esophagus-stomach model and the efficacy and safety of POEM for patients with achalasia were evaluated.MethodsThe ex-vivo esophagus-stomach was obtained and the pylorus was closed by hemostatic forceps.The entrance of the esophagus was fixed to foamed plastics.To perform POEM,a submucosal tunnel was created,after which the circular muscle layer was dissected and the mucosal entry was finally closed with clips.After successful animal experiment,we performed POEM on 4 patients with achalasia.Results POEM was completed in 5 porcine training models,in which 2 procedures were successful without any complication,2 were complicated with perforation in muscularis propria layer and 1 with rupture in mucosal layer.POEM was successfully performed in 4 patients with achalasia,with a mean operation time of 110min.The mean length of the submucosal tunnel was 10.5cm ( ranging 8-11 cm) and the mean length of myotomy of circular muscle layer was 7 cm (ranging 5-8 cm).The resting pressure of lower esophageal sphincter (LES) decreased from 52.4 mm Hg before POEM to 19.9 mm Hg.Massive bleeding occurred at the gastroesophageal junction in the first case and perforation occurred in mucosal layer during endoscopic hemostasis.All patients were followed up for 1-4 months,and the symptom of dysphasia was relieved significantly.ConclusionThe ex-vivo esophagus-stomach model can be used as training model for procedure of POEM,enabling endoscopists with enough experience for its use in patients.POEM is an effective therapy for achalasia,while the long-term efficacy and managements for complications are still to be elucidated.

Objective To observe the effects of casein and excessive iodine on histomorphalogY and ultrastructure of mouse thymicL Methods Based on 2 × 3 factorial design,the experimental mice were divided into 6 groupg Animal models were estabhshed by feeding the mice with different levels of iodine water and casein food.The levels of iodine were 50,600 μg/L in drinking water and 0(Ⅰ),10%(Ⅱ),20%(Ⅲ)of casein in food respectively.After 12 months,the thyroid weight was measured and the morphology of thyroid was observed under optical and electron microscope.Results Factorial analysis showed that iodine factors obviously affected the thyroid absolute and relative weiights of mice(F=16.23,9.47,P＜0.01),and there was interaction between casein and iodine(F=5.29,4.68,P＜0.01 or＜0.05).Compared wiht 150Ⅰ[(5.91±0.82)rag,(117.0±22.2)mg/kg]and 50Ⅲ[(4.90±0.63)rag,(106.1±13.3)mg/kg]groups.thyroid absolute and relative weights of the mice increased in 600 Ⅰ[(7.60±2.40)mg,(143.3±43.2)mg/kg]and 600Ⅲ[(8.63±1.88)mg,(166.2±39.4)mg/kg]groups(P＜0.05 or＜0.01),respectively.But compared with 600 Ⅰ and 600Ⅲ groups.they were reduced obviously in 600Ⅱ[(5.76±1.13)mg,(109.8±16.5)mg/kg]group(P＜0.05 or＜O.01).Colloid goiter,lymphocyte infiltration were found,some of the follicles epithelial cells appeared active under light and electron microscope in iodine excels group,which,however,decreased obviously along with the increase of casein dose.Conclusions Long-term excessive iodine may cause colloid goiter and inflammation injury of mice,possibly leading the development of thyroiditis in mice,which may be partly reduced by casein.