We analyzed the anticancer effect and mechanism of the novel indoleamine 2,‍3-dioxygenase 1 (IDO1) inhibitor NLG-919 combined with temozolomide (TMZ) on human glioma cell lines. The anti-tumor activity of NLG-919 and temozolomide after single and combined treatments was detected by MTT assay. Colony formation assay, invasion assay and migration assays were used to detect the effects of NLG-919 and temozolomide alone or in combination on proliferation, invasion and migration of human glioma cells. A flow cytometry assay was used to detect cell apoptosis, cell cycle arrest, reactive oxygen species (ROS) production and mitochondrial membrane potential damage (JC-1). An immunofluorescence assay was used to detect the expression level of IDO1 and HPLC was used to detect the expression level of L-kynurenine (Kyn) to explore the anti-tumor mechanism of NLG-919 and temozolomide. The results show that NLG-919 had a weak in vitro inhibitory effect compared to that of temozolomide. The IC₅₀ of NLG-919 on U251 cells and U87 after 72 h was 26.9 and 30.7 μmol·L^-1, respectively. However, when NLG-919 was used in combination with temozolomide, its anti-glioma activity was significantly increased. Compared with the single treatment, the combination treatment had a potent ability to inhibit proliferation, invasion and migration of glioma cells. Combination treatment improved the capacity of temozolomide to induce cell cycle arrest and inhibit the growth of glioma cells. NLG-919 significantly down-regulated the expression and activity of IDO1 in glioma cells, and the inhibitory effect was improved after combination with temozolomide, and effectively blocked the production of Kyn through the metabolism of L-tryptophan (Trp). In conclusion, the IDO1 inhibitor NLG-919 and temozolomide showed synergistic effects in the anticancer therapy of human glioma cell lines.

Cervical Ripening ; Female ; Humans ; Integrative Medicine ; Pregnancy

An organic solvent tolerant isolate A213 originating from soil samples were successfully isolated via direct plating method using 10g/L of toluene as the sole carbon source and transparent cycle plate assay method.It was identified as Yarrowia based on its characteris- tics.The results in shake flask cultivation showed that the suitable tipase producing media were(g/L):yeast extract 40,vegetable oil 10, MgSO_4?7H_2O1,KH_2PO_4 5.Under optimal culture conditions (27℃and pH 6.5 ),the maximal lipase activity could reach 67.8 IU/ mL The optimal pH and temperature for the hydrolysis of p-nitrophenyl acetate by crude lipase were pH6.5 and 40℃The enzyme was sta- ble under 70℃and pH 5.5～8.5.Then isolate A213 was found to produce the lipase which can synthesize L-ascorbyl palmitate in tert-amyl alcohol validated by the thin-layer chromatography.

Objective To investigate the incidence of Keshan disease(KSD) in Shandong province and to supply evidence for scientific control of the disease.Methods According to the scheme of KSD monitoring in Shandong province,the KSD cases were searched in 7 counties,and representative 3 counties and 6 villages were selected as key monitoring sites.In each site,about 420 residents were checked by asking detailed disease history,physical examination,and electrocardiography (ECG) tracings.Suspected cardiac abnormalities were taken chest posteroanterior X-ray film.At the same time,residents hair and food samples were collected to detect selenium levels in internal and external environments,and residents' income and per capita share of grain and other basic information were collected.Results ①Two hundred and fifty-nine medical units were searched,1132 cases of myocardial disease were found out and 638 suspected cases were identified and 142 chronic KSD cases were diagnosed.②In the 6 monitoring sites,2538 residents were surveyed and 91 cases of KSD were detected(of which 77 cases of potential,14 cases of chronic),the detection rate was 3.58％.A total of 2127 residents were traced ECG and the incidence of abnormal ECG was 24.5％ (521/2127),of which ST-T changes,T-wave changes,sinus bradycardia,sinus arrhymia,sinus tachycardia,and atrial premature beats et al were more common.Of the 75 X-ray films,39 cases had enlarged heart(in which 21 of mild,13 of moderate,5 of severe).③A total of 406 hair and grain samples were collected,respectively,and the selenium content of hair was approaching the level of appropriate,and the selenium content of food was still low.The annual per capita incomes of each site were between 3000 - 5900 Yuan,and residents main staple food was flour.Conclusions KSD in Shandong province is in a relatively stable situation.But latent and chronic KSD cases can still be detected.The internal environment selenium levels are elevated since the local living standards and dietary nutrition are improved.

Four kinds of ionic liquids were adopted to analyze the content of rubimaillin and alizarin in Rubia cordifolia roots with ultrasonic-assisted extraction coupled with HPLC. The chromatographic column, Purospher star RP-C18 (4.6 mm x 250 mm, 5 microm), was used. Methanol and 0.4% acetic acid-water as mobile phase with flow rate at 0.85 mL min(-1), gradient elution, detection wavelength at 250 nm, chromatographic column temperature was controlled at room temperature. The result showed that rubimaillin and alizarin had the highest extraction yield when the [ HMIM] PF6methanol solution concentration of 0.6 mol x L(-1) as extraction solvent and the conditions were solid-liquid ratio of 1:80 (g x mL(-1)). Under the optimal extraction conditions, the content of alizarin from 0.01 to 0.04 microg showed a good linearity (r = 0.9999), the average recovery was 97.12%, the content of rubimaillin from 0.41 to 1.35 microg showed a good linearity (r = 0.9999), the average recovery was 98.10%. This experiment adopted environmentally friendly reagent as extraction solvent, the extraction efficiency was improved, and the environmental pollution caused by organic solvent was avoided, the harm of human body aslo was reduced. This method was simple and reliable, its repeatability was also very good, which had an important significance in the study of traditional Chinese medicine active ingredient extraction methods.
Anthraquinones ; analysis ; Chromatography, Reverse-Phase ; methods ; Ionic Liquids ; chemistry ; Pyrans ; analysis ; Rubia ; chemistry ; Ultrasonics

Abstract?AIM: To evaluate the visual acuity, visual function, q uality of lfi e, and cost/effectiveness of cataract surgery in patients with low soc ioeconomics tatus ( LSES ) who received government subsidies for free cataract surgery.?METHODS: Retrospectively, 334 eyes of 334 patient s were reviewed. Visual function and quality of l ife questionnaires we re available in 83 patie nts. The cost/effectiveness of cataract surgery was analyzed in 225 patients with LSES and 12 0 patients who rec eived standard cataract surgery. Mutl iple linear regression anal ysis and logistic regression analysis were used to assess the factors affecting the postoperative visual acuity.?RESULTS: At 1wk postoperatively, uncorrected visual acuity ( UCVA ) was improved significantly compared to these preoperait vely (P<0.50 ), 235 eyes (70.4%) had UCVA of 20/40 or better, and 16 eyes (4.8%) had UC VA wor se than 20/400. Multiple linear regresis on ana lysis revealed that other ocular diseases and cataract classification wer e factors contributing to po stop erative UC VA. Logistic regression analysis showed that low preoperative visual ac uti y and other ocular diseases were risk factors of postopera tive low vision, and the odds ratio (95%confidence int erval) values were 6.5 (2.8-14.8) and 1.3 (1.0-1.6), respe ctively.Visual fun ction and quality of life were significantly improved after the surgery. Th e cost/effetc iveness of c ataract su rgery in patients with LSES was lower than that in standard cataract patients.?CONCLUSION: Visual acuity and visual function were significantly better after the surgery in catara ct patients wti h LSES, and the operation cost was low.Quality of life in these patients was significantly improved.

Four kinds of ionic liquids [BMIM] Br, [BMIM] BF4, [BMIM] PF6, [HMIM] PF6 were used to analyze the content of oleanic acid and paeoniflorin in Paeonia lactiflora with ultrasonic-assisted extraction coupled with HPLC. The chromatographic column, Purospher star RP-C18 (4.6 mm x 250 mm, 5 μm), was used. Acetonitrile and water (90:10) as mobile phase was used to determine the content of oleanic acid with a gradient elution and flow rate at 1.00 mL · min(-1), detection wavelength at 210 nm, chromatographic column temperature at room temperature. Paeoniflorin content was determined using acetonitrile and water (18:82) as mobile phase with a gradient elution and flow rate at 1.00 mL · min(-1), detection wavelength at 250 nm, the chromatographic column temperature at room temperature. The result show that oleanic acid has the highest extraction yield when the conditions are solid-liquid ratio of 1:80 (g · mL(-1)), and the [BMIM] Br methanol solution concentration of 0.6 mol · L(-1). Under the optimal extraction conditions, the content of oleanic acid from 0.24 to 3.76 μg showed a good linearity (r = 0.9999), the average recovery was 97.20%. Paeoniflorin has the highest extraction yield when the conditions are solid-liquid ratio of 1:130 (g · mL(-1)), and the [C4 MIM] PF6 methanol solution concentration of 0.6 mol · L(-1). Under the optimal extraction conditions, paeoniflorin content from 0.42 to 4.20 μg showed a good lin- earity (r = 1.000), the average recovery was 98.84%. This method is simple and reliable, its repeatability is also very good. It has important significance in the study P. lactiflora of ionic liquid microextraction.
Chromatography, Reverse-Phase ; methods ; Glucosides ; analysis ; Ionic Liquids ; chemistry ; Monoterpenes ; analysis ; Oleanolic Acid ; analysis ; Paeonia ; chemistry ; Ultrasonics

Objective To compare the efficacy of 18F-FDG PET/CT, 99Tcm-MDP bone scintigraphy (BS), and combination of the two techniques (PET/CT + BS) for detecting bone metastasis by ROC curve analysis. Methods All 296 patients with various cancers, who underwent both 99Tcm-MDP BS and 18F-FDG PET/CT within two months, were retrospectively analyzed. These images were interpreted according to 5-point scale (0: definitely negative, 1: probably negative, 2: equivocal, 3: probably positive, 4:definitely positive for bone metastasis), and the scale of PET/CT + BS was the sum of PET/CT and BS. In light of the confirmed diagnosis derived from pathology or follow-up, ROC curve analysis was performed.The area under the ROC curve (AUC) was compared by z-test. Results Of 296 cases, 61 (20.6%) were confirmed as bone metastases and 235 (79.4%) were negative. The AUC were 0. 919 (95% confidence interval (95% CI) :0. 867 - 0. 971) for BS, 0. 949 (95% CI: 0. 906 - 0. 991) for PET/CT, and 0. 994 (95% CI: 0.988-0.999) for PET/CT + BS, rctrospectively. The AUC of PET/CT + BS was statistically significantly larger than that of BS (z=2. 866, P=0.004) or PET/CT (z =2.027, P=0.043), while the AUC of PET/CT was larger than that of BS, but no statistically significance (z = 0. 881, P = 0. 378) was showed. The optimal sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value(NPV) were 90. 2% (55/61), 85. 1% (200/235), 86. 1% (255/296), 61. 1% (55/90), 97. 1%(200/206) for BS, 88.5% (54/61), 97.0% (228/235), 95.3% (282/296), 88.5% (54/61), 97.0% for PET/CT, and 98.4% (60/61), 95.7% (225/235), 96.3% (285/296), 85.7% (60/70) for PET/CT + BS,respectively. The specificity (χ2 = 19.862, P<0. 001), accuracy (χ2 = 23. 361, P<0.001) and PPV (χ2 =11. 791, P =0.001) of PET/CT + BS were significantly higher than those of BS, the sensitivity of PET/CT +BS was significantly higher than that of PET/CT (χ2 =4.167, P=0.031). Compared with BS, PET/CT had a higher specificity (χ2 = 19.600, P<0. 001), accuracy (χ2 = 13. 755, P <0. 001), PPV (χ2 = 13. 608, P <0. 001), but their sensitivity showed no statistically significant difference (χ2 = 0, P = 1. 000). Conclusions The efficacy of 18F-FDG PET/CT for detecting malignant bone metastasis was superior to that of 99Tcm-MDP BS alone. The detection ability can be obviously improved by combination of the two techniques.

OBJECTIVETo evaluate the inhibitory effect of genistin combined with anastrozole on the growth and apoptosis of breast tumor tissue, and to study their anti-cancer mechanism by using the model of 7,12-dimethylbenz [alpha] anthracene (DMBA)-induced mammary tumors following ovariectomy in Sprague-Dawley (SD) rats.

METHODSThe DMBA induced postmenopausal SD rats were randomly divided into the control group, the genistein group, the anastrozole group, and the genistein combined with anastrozole group. The growth of tumors was observed in each group. The proliferation index and apoptosis index of tumor cells were determined. Moreover, estradiol (E2) and 17beta-HSD1 mRNA levels were determined by ELISA and RT-PCR respectively.

RESULTSThe tumor growth was inhibited in the genistein group and the anastrozole group. The inhibitory ratio was significantly higher in the genistein combined with anastrozole group (P < 0.05). Compared with the control group, levels of E2 and 17beta-HSD1 mRNA decreased more significantly in the genistein combined with anastrozole group (P < 0.05).

CONCLUSIONSGenistein could suppress the growth of mammary tumors in postmenopausal rats. It showed synergistic effect when combined with anastrozole, which resulted in reduced levels of E2 and 17beta-HSD1 mRNA. It had inhibitory effect on the growth of breast tumors.

17-Hydroxysteroid Dehydrogenases ; metabolism ; Animals ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Estradiol ; metabolism ; Female ; Genistein ; administration & dosage ; pharmacology ; Mammary Neoplasms, Experimental ; chemically induced ; pathology ; Nitriles ; administration & dosage ; pharmacology ; Ovariectomy ; Postmenopause ; Rats ; Rats, Sprague-Dawley ; Triazoles ; administration & dosage ; pharmacology

0.05).Mean time for lesion healing in immunocompromised and immunocompenent mice was 36.8 d and 29.0 d respectively(P0.05).Conclusions Primary cutaneous cryptococcosis may lead to dissemination of the infection in immunocompromised mice and our data suggest that skin is a possible route for dissemination of cryptococcal infection.