Inositol requiring enzyme 1 alpha (IRE1α), a widespread transmembrane protein in mammals, is an endoplasmic reticulum stress (ER stress) receptor. Among the three signaling pathways of the unfolded protein response (UPR), the IRE1α pathway is the most conservative. And there is a growing body of evidence that the occurrence and development of tumors is closely related to the over-expression of IRE1α. Therefore, the study of the IRE1α inhibitors is of great significance to the discovery of new anti-tumor drugs and has been attracting more and more attention. In the hope of providing ideas for the research of targeting IRE1α for cancer therapy, this paper reviewed the data of representative IRE1α inhibitors, including inhibitory activity, the mechanism of action, structural characteristics, and so on.

A comprehensive HPLC-DAD-MS method was developed to study the chemical components of semi-bionic extract of Coptis-Evodia herb couple. The extract was isolated on a Hypersil BDS C18 column (4.6 mm x 200 mm, 5 microm) using acetonitrile-ammonium formic buffer as mobile phase by gradient elution. Detection was performed on DAD and MS equipped with an electrospray ionization (ESI) source by full scan and product full scan on positive mode. The chromatogram of Coptis-Evodia showed seventeen main peaks, eight of which were from Evodia while the others were from Coptis. By comparison of the retention time, the on-line UV spectra and MS spectra, four peaks were identified as jatrorrhizine, hydroxevodiamine, palmatine and berberine, and three peaks were deduced as epiberberine, columbamine and coptisine. In addition, berberine and palmatine were quantitatively determined. No new component was created in the semi-bionic extract of the herb couple, yet the solubilities of berberine and palmatine decreased.
Berberine ; analogs & derivatives ; chemistry ; isolation & purification ; Berberine Alkaloids ; chemistry ; isolation & purification ; Chromatography, High Pressure Liquid ; methods ; Coptis ; chemistry ; Drugs, Chinese Herbal ; Evodia ; chemistry ; Plant Extracts ; chemistry ; Spectrometry, Mass, Electrospray Ionization

Humans ; Immunoglobulin D ; Multiple Myeloma ; Rupture, Spontaneous ; Spleen

OBJECTIVETo study the 3, 4- dinitro-furazan-based oxidation furazan (DNTF) of sub-acute toxicity and chronic toxicity, to determine the acute toxicity classification DNTF, the nature of toxic effects and major target organ for the development provide the basis for occupational exposure limits.

METHODS( 1) Acute toxicity: The oral gavage method once infected, symptoms of poisoning of animals observed to calculate the LD50DNTF and 95% confidence limits. ( 2) sub-chronic experiment: selection of 96 healthy SD rats were randomly divided into four groups, doses of 25, 56.2, 125 mg/kg and the negative control group, Exposure for ninety days,five days a week, once a day, The rats were killed at end of Exposure, heart, liver, spleen, lung, kidney, brain,testis, uterus were taken to observe the pathological changes.

RESULTS( 1) Acute oral toxicity test results indicate that DNTF rat oral LD50 greater than 5000 mg/kg, DNTF mice treated by oral LD50 4589 mg/kg, 95%confidence limit for the 4026-5230 mg/kg, Acute toxicity grade level is low toxicity compounds. (2) Sub-chronic toxicity experiment, the high-dose male rats, high, medium and low-dose group female rats weight gain than the negative control group, compared with the control group, the difference was statistically significant (P<0.05).125 mg/kg of serum alanine aminotransferase, aspartate aminotransferase was significantly higher. 125 mg/kg dose groups, liver, kidney, lung, testicular factor was significantly higher. Liver, kidney, lung histological examination showed obvious morphological changes.

CONCLUSIONAcute toxicity grade DNTF low toxicity level compounds, target organ toxicity of liver, kidney and lung.

Animals ; Female ; Lethal Dose 50 ; Male ; Mice ; Nitrofurazone ; analogs & derivatives ; toxicity ; Oxadiazoles ; toxicity ; Rats ; Rats, Sprague-Dawley ; Toxicity Tests

OBJECTIVETo observe the therapeutic effect of moxibustion and exercise comprehensive scheme intervention for children with short stature of deficience of the kidney essence.

METHODSTwenty four cases of children in 12 to 14 years old were selected, 12 male and 12 female, they were treated with comprehensive therapy of exercise therapy and moxibustion. Running and jumping were selected as main exercise therapy, it became a suitable exercise amount when the heart rate reach to 150 to 170 times per minute, thrice each week, 35 to 45 minutes each time. After exercises they were treated with moxibustion, Qihai (CV 6), Guanyuan (CV 4), Zusanli (ST 36), Dazhu (BL 11), Xuanzhong (GB 39), Geshu (BL 17) etc. were selected. After treatment for half a year, the changes of the body height, body weight, bone age(BA), growth hormone (GH), testosterone (T) and estradiol (E2) were compared before and after treatment.

RESULTSThe body height and bone age of the boys and girls were significantly higher than those before treatment (all P<0.05), the growth of body height was more than 4 cm, the growth of bone age was more than 0.5 years old in half a year; the testosterone of all children was significantly increased (all P<0.05), and there were no significant differences in body weight, GH and E2 compared to those before treatment (all P>0.05).

CONCLUSIONMoxbustion and exercise comprehensive scheme can effectively improve the children with short stature of deficience of the kidney essence, the mechanism is related to the improving of the testosterone level.

Adolescent ; Body Height ; Child ; Estradiol ; metabolism ; Exercise Therapy ; Female ; Growth Disorders ; metabolism ; physiopathology ; therapy ; Human Growth Hormone ; metabolism ; Humans ; Kidney ; physiopathology ; Male ; Moxibustion ; Testosterone ; metabolism ; Treatment Outcome

OBJECTIVETo study the teratogenicity of new high-energy compounds, 3, 4 two furazan-based oxidation furazan (DNTF) and the impact on human health, occupational exposure limits were provided for the following research.

METHODSPregnant SD rats were randomly divided into five groups by Standard teratogenicity test, including three dose groups (5.0, 15.8, 50.0 mg/kg), the negative control (vegetable oil), and the positive control group (CP 10.0 mg/kg). Each 10 to 15 rats were in one group. Gavage was consecutive for rats during pregnancy 7 ∼ 12 d and then sacrifice after 20 d.

RESULTSThere were no significantly difference between the three dose groups and negative controls in the pregnancy rate, the weight of pregnant rats, fetal weight, fetal growth, fetal malformation rate and internal organs,

CONCLUSIONThere were no maternal toxicity, embryo toxicity and teratogenicity for rats when DNTF in the range 5.0 ∼ 50.0 mg/kg.

Animals ; Female ; Nitrofurazone ; toxicity ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Teratogens

OBJECTIVETo study the mutagenicity and teratogenicity induced by ammonium dinitramide(ADN).

METHODSAccording to technical specifications for toxicity determination of chemicals, Salmonella typhimurium reverse mutation assay (Ames assay), in vivo mammalian erythrocyte micronucleus test, sperm malformation test and teratogenesis test were used to detect the mutagenicity and teratogenicity induced by AND.

RESULTSWhen the exposure doses of AND were 8-5000 pg/plate, the result of Ames assay was negative. As compared with control group, the micronucleus rate of mice exposed to 113.8 mg/kg AND significantly increased(P<0.05), the sperm malformation rates of mice exposed to 54.4-272.0 mg/kg AND did not increased significantly. The survival rate of fetuses decreased, the rate of assimilated fetuses increased, the rate of fetus sternum agenesis enhanced in mice exposed to 319 mg/kg AND, as compared with controls. The rates of in the 4th-6th fetus sternum agenesis in groups exposed to 21.3, 79.7 and 319 mg/kg AND were higher than that in control group. The malformation rate of fetus bowels in groups exposed to 319 mg/kg AND was higher than that in control group. The teratogenic index of ADN was 30.

CONCLUSIONAND may be a mutagen and induce the teratogenic effect.

Animals ; Embryo, Mammalian ; drug effects ; pathology ; Female ; Male ; Mice ; Mice, Inbred Strains ; Micronucleus Tests ; Mutagenicity Tests ; Nitrites ; toxicity ; Pregnancy ; Quaternary Ammonium Compounds ; toxicity ; Spermatozoa ; drug effects ; pathology ; Sternum ; drug effects ; pathology

OBJECTIVETo study the acute, subacute and subchronic toxicity induced by ammonium dinitramide (ADN), and to ascertain the gradation and target organs of acute toxicity induced by AND.

METHODSAccording to technical specifications for toxicity determination of chemicals, the oral tests for acute, subacute and subchronic toxicity induced by AND were performed for 90 days.

RESULTSThe oral LDx for mouse and rat was 568.9 mg/kg and 616.6 mg/kg ADN respectively. The gradation of acute toxicity induced by AND was low level. The results of oral subacute and subchronic toxicity tests (for 28 and 90 days) showed that a gain in weight in group exposed to 123 mg/kg AND was significantly lower than that in control group (P<0.05), the TBIL and ALT in group exposed to 61.6 and 123 mg/kg AND significantly increased and the ratio of liver weight to body weight obviously decreased, as compared with control group, the number of animals with hepatic pathological changes in group exposed to 61.6 and 123 mg/kg AND was significantly higher than that in control group (P<0.05).

CONCLUSIONThe gradation of acute toxicity induced by ADN was low level. When the exposure dose of AND was 30.8 mg/kg, the adverse effect was not observed, and the target organ was liver.

Animals ; Body Weight ; Female ; Liver ; drug effects ; pathology ; Male ; Mice ; Mice, Inbred Strains ; Nitrites ; toxicity ; Quaternary Ammonium Compounds ; toxicity ; Rats ; Rats, Sprague-Dawley ; Toxicity Tests, Acute ; Toxicity Tests, Subchronic

Objective　To ascertain the natural infection rate of hemorrhagic fever with renal syndrome virus (HFRSV) among its hosts and the type of the natural foci for providing some baseline data for the immigrant health and epidemic prevention of the Three-Gorge region. Methods　Epidemiological survey on the field was performed including epidemiological data collection, ecology of rodents and pathogen detection. HFRS virus antigen of hosts were detected by the direct immunofluorescent assay (DIFA) technique and determination of HFRSV-RNA by ISH were carried out from HFRSV-Ag-positive animals. Results　HFRSV-Ag-positive animals were found in 5 migration areas ie Baitao Town of Fuling Section, Wansheng Village of Fengjie County and Dachang Town of Wushan County. The positive hosts were as follows, Rattus Norvegicus, Apodemus agrarius, Anourusurex squamipes, Mus musculus and Rattus flavipectus. The positive rate of HFRSV in the mice of 5 migration areas were 19.4%, 17.0%, 14.0%, 13.7%, and 8.5% respectively. The results showed that the lung tissues of some hosts in all five migration areas were HFRSV-RNA-positive. Baitao Town and Peishi Town were attributed to mixture type epidemic areas while. Kangle Town, Wansheng Village and Dachang Town were domestic rats type epidemic areas. Conclusion　This study shows that the five migration areas are natural epidemic foci of HFRS. It is predicted that maximum risk of HFRS breakout or epidemic may take place after the completion of the San Xia Reservoir(the Three-Gorges Reservoir), which results from rodent moving toward higher land. Therefore, deratization and preventive measures for rat are important in migration areas.