Micafungin exerts antitumor effect on breast cancer and osteosarcoma through preventing EMT in tumor cells in an USP7/AKT/GSK-3ß pathway-dependent manner.

Breast cancer and osteosarcoma are common cancers in women and children, respectively, but ideal drugs for treating patients with breast cancer or osteosarcoma remain to be found. Micafungin is an antifungal drug with antitumor activity on leukemia. Based on the notion of drug repurposing, this study aims to evaluate the antitumor effects of micafungin on breast cancer and osteosarcoma in vitro and in vivo, and to elucidate the underlying mechanisms. Five breast cancer cell lines (MDA-MB-231, BT-549, SK-BR-3, MCF-7, and 4T1) and one osteosarcoma cell line (143B) were chosen for the in vitro studies. Micafungin exerted an inhibitory effect on the viability of all cell lines, and MCF-7 cells were most sensitive to micafungin among the breast cancer cell lines. In addition, micafungin showed an inhibitory effect on the proliferation, clone formation, and migration in MCF7 and 143B cells. The inhibitory effect of micafungin on the growth of breast cancer and osteosarcoma was further confirmed with xenograft tumor mouse models. To explore the underlying mechanisms, the effect of micafungin on epithelial-mesenchymal transition (EMT) was examined. As expected, the levels of matrix metalloproteinase 9 and vimentin in MCF-7 and 143B cells were notably reduced in the presence of micafungin, concomitant with the decreased levels of ubiquitin-specific protease 7 (USP7), p-AKT, and p-GSK-3ß. Based on these observations, we conclude that micafungin exerts antitumor effect on breast cancer and osteosarcoma through preventing EMT in an USP7/AKT/GSK-3ß pathway-dependent manner.

Evaluation on the efficacy of moxifloxacin hydrochloride based on physiological pharmacokinetic models / 药学学报

This study is to establish and validation in vivo models of moxifloxacin based on the theory of physiologically based pharmacokinetics (PBPK), and then to predict the distribution of moxifloxacin in human venous return and organ such as lung, spleen and so on. The efficacy of moxifloxacin and its pharmaceutical preparations were quantified by comparing the pharmacokinetic parameters with the minimum inhibitory concentration of related pathogenic bacterium. The results showed that the anti-infection efficacy of pharmaceutical moxifloxacin preparation in the corresponding organs was basically the same. The PBPK model of moxifloxacin preparations can be more accurately described the pharmacokinetic of anti-infective drugs in human, it is suitable for the efficacy evaluation of anti-infective drugs and provides a strong basis for the corresponding scientific research and scientific supervision.

Research on polymer impurities in cefazolin sodium raw materials and products / 药学学报

Research on polymer impurities has always been important in the quality control of cephalosporins. Research on polymers in cephalosporins that lack active amino groups on the C-7 side chain has not been reported. Therefore, our study used cefazolin sodium, which is widely used in the clinic, as an example. The polymer in cefazolin sodium and its product "cefazolin sodium pentahydrate for injection" was analyzed by column switching liquid chromatography-high resolution mass spectrometry. Two polymer impurity peaks were detected and the possible structures of these polymers were suggested. Through two-dimensional liquid chromatography, the chromatographic peaks following Sephadex gel chromatography and high-performance gel chromatography were compared to those obtained by reverse high-performance liquid chromatography (HPLC) for cefazolin sodium as reported in the Chinese Pharmacopoeia. The HPLC method proves more suitable for polymer detection than Sephadex gel chromatography and high-performance gel chromatography. The method of polymer detection for cefazolin sodium was established using the method of related substances HPLC as described in the Chinese Pharmacopoeia.

Si-thiol supported atomic-scale palladium as efficient and recyclable catalyst for Suzuki coupling reaction.

Atomic-scale catalysts leverage the advantages of both heterogeneous catalysts for their stability and reusability and homogeneous catalysts for their isolated active sites. Here, a palladium catalyst supported by Si-thiol, a commercially available mercaptopropyl-modified and TMS-passivated amorphous silica, was synthesized and characterized by SEM,TEM, aberration-corrected STEM-HAADF, XRD, FT-IR and XPS. Statistical analysis revealed that the catalytic Pd species predominantly consisted of intermediate sized nanoparticles (<2 nm), small amounts of essentially isolated atoms (ca. 0.1 nm), and limited amounts of somewhat larger nanoparticles (<5 nm). The nanoscale atomic clusters dominated the reactivity and served as the key active sites for Suzuki coupling. The outcomes of the reaction were greatly affected by the choice of solvents, and Pd/Si-thiol was demonstrated to be reusable for more than three times without a noticeable loss of catalytic activity. [Formula: see text].

Analysis of polymer impurities in cefixime raw materials and preparations / 药学学报

To establish a method for the determination of polymer impurities in cefixime raw materials and preparations, a cefixime degradation solution containing polymer impurities was prepared by forced polymerization. Polymer impurities in the degradation solution were separated and identified by high performance gel chromatography and the column switching-LC-MSn method. A new RP-HPLC method for cefixime polymer was established and validated with a Phenomenex Gemini-C18 column using a mobile phase gradient elution of 0.5% formic acid-water solution and 0.5% formic acid-acetonitrile solution. The results showed that when using this high performance gel chromatography method some small molecular weight impurities were co-eluted with the polymers, resulting in a poor specificity and poor quantitative accuracy. But when using the RP-HPLC method, three polymer impurities were detected with good specificity, sensitivity and robustness, including two cefixime dimers, and dehydrate dimer. Therefore, the described RP-HPLC method is suitable for the quality control of polymer impurities in cefixime, and cefixime degradation solution can be used as suitable solution for analysis of cefixime polymers.

Analysis of polymer impurities in ceftazidime raw materials and preparations / 药学学报

To establish a method for the determination of polymer impurities in ceftazidime raw materials and preparations, a ceftazidime degradation solution containing polymer impurities was prepared by forced polymerization. Polymer impurities in the degradation solution were separated and identified by high performance gel chromatography and the column switching-LC-MSn method. A new RP-HPLC method for ceftazidime polymer was established and validated with a Phenomenex Gemini-C18 column using a mobile phase gradient elution of 0.02 mol·L-1 phosphate buffer, methanol and acetonitrile. The results showed that when using this high performance gel chromatography method some small molecular weight impurities were co-eluted with the polymers, resulting in a poor specificity and poor quantitative accuracy. But when using the RP-HPLC method, four polymer impurities were detected in the 25-45 min time range with good specificity, sensitivity and robustness, including two ceftazidime dimers, trimers, and derivatives. Therefore, the described RP-HPLC method is suitable for the quality control of polymer impurities in ceftazidime, and ceftazidime degradation solution can be used as suitable solution for analysis of ceftazidime polymers.

Curative effect of mouse nerve growth factor and its influence on levels of BDNF, IGF-1, and IL-33 in patients with acute cerebral infarction / 药物评价研究

Objective To observe the curative effect of mouse nerve growth factor and its influence on levels of BDNF,IGF-1,and IL-33 in patients with acute cerebral infarction.Methods Totally 106 cases of patients with acute cerebral infarction were chosen as the research objects between October 2015 and February 2017 in Fourth People's Hospital of Langfang City.According to digital list method,the patients were randomly divided into treatment group and control group,53 cases in each group.The patients in two groups were treated with conventional medicine of acute cerebral infarction,and the patients in treatment group were added to mNGF on the basis of conventional drugs,im injection,18 μg each time,once daily.The patients in control group were not added to NGF treatment,and the patients in two groups were treated for 14 d.Before and after treatment,the degrees of neural function defect in two groups were scored according to NIH Stroke Scale (NIHSS),serum levels of brain-derived neurotrophic factor (BDNF),insulin-like growth factor-1 (IGF-1) and interleukin-33 (IL-33) were determinated using enzyme-linked immunosorbent method.Results Compared with those before treatment,NIHSS scores decreased (P ＜ 0.05) after 14 d of treatment in two groups,but the reduced value in treatment group was obviously higher than that in control group (P ＜ 0.05).After treatment,the total effective rate (93.4％) of treatment group was better than that of control group (46.6％),and the difference was statistically significant (P ＜ 0.05).Compared with before treatment,serum levels of BDNF and IGF-1 rised (P ＜ 0.05),IL-33 decreased (P ＜ 0.05) after 14 d of treatment in two groups,but the changes in treatment group were significantly greater than those in control group (P ＜ 0.05).Conclusion mNGF can effectively reduce the severity of nervous functional defects,and effectively increase expression levels of BDNF and IGF 1 and decreasedexpression level ofIL-33.

Curative effect of mouse nerve growth factor and its influence on levels of BDNF, IGF-1, and IL-33 in patients with acute cerebral infarction / 药物评价研究

Objective To observe the curative effect of mouse nerve growth factor and its influence on levels of BDNF,IGF-1,and IL-33 in patients with acute cerebral infarction.Methods Totally 106 cases of patients with acute cerebral infarction were chosen as the research objects between October 2015 and February 2017 in Fourth People's Hospital of Langfang City.According to digital list method,the patients were randomly divided into treatment group and control group,53 cases in each group.The patients in two groups were treated with conventional medicine of acute cerebral infarction,and the patients in treatment group were added to mNGF on the basis of conventional drugs,im injection,18 μg each time,once daily.The patients in control group were not added to NGF treatment,and the patients in two groups were treated for 14 d.Before and after treatment,the degrees of neural function defect in two groups were scored according to NIH Stroke Scale (NIHSS),serum levels of brain-derived neurotrophic factor (BDNF),insulin-like growth factor-1 (IGF-1) and interleukin-33 (IL-33) were determinated using enzyme-linked immunosorbent method.Results Compared with those before treatment,NIHSS scores decreased (P ＜ 0.05) after 14 d of treatment in two groups,but the reduced value in treatment group was obviously higher than that in control group (P ＜ 0.05).After treatment,the total effective rate (93.4％) of treatment group was better than that of control group (46.6％),and the difference was statistically significant (P ＜ 0.05).Compared with before treatment,serum levels of BDNF and IGF-1 rised (P ＜ 0.05),IL-33 decreased (P ＜ 0.05) after 14 d of treatment in two groups,but the changes in treatment group were significantly greater than those in control group (P ＜ 0.05).Conclusion mNGF can effectively reduce the severity of nervous functional defects,and effectively increase expression levels of BDNF and IGF 1 and decreasedexpression level ofIL-33.

Subtype classification of ceftriaxone sodium and its influence on the quality of product / 药学学报

Powder X-ray diffraction (PXRD) technology combined with cluster analysis method was used to classify 75 batches of crystalline ceftriaxone sodium into subtypes, the crystalline characteristics of each subtype were measured with scanning electron microscope (SEM). By comparing some parameters of these subtypes correlated to crystallization process of ceftriaxone sodium, such as salification rate, water content in different subtypes, as well as by studying different lattice stabilities, different compatibilities with rubber closures during accelerated stability tests, the key point to improve the quality of domestic ceftriaxone sodium was disclosed. The results of this paper indicated that the fine structure of the products could be controlled well by improving the salification and crystallization process. As a result, the subtype II of ceftriaxone sodium with high stability can be produced.

Physical and chemical characteristics of a new cefazolin sodium hydrate crystal / 药学学报

One kind of new cefazolin sodium hydrate crystal was obtained in the isopropyl alcohol - water system. There are two symmetry independent molecules in the asymmetric unit, both being well ordered in the lattice, and ten independent water positions but generally four to six (mean five) water molecules and one sodium ion present in the unit cell structure. Huge solvent tunnels can be found. Again there are two general regions of water molecules, those in the large solvent tunnels and those in proximity of the sodium ion and the tetrazole moieties of the drug molecule. The physical and chemical characteristics of the new cefazolin sodium hydrate crystal are similar to that of the alpha-form cefazolin sodium crystal, and the new crystal has better chemical stability than amorphous cefazolin sodium powder.

Synthesis of fluorinated 1-(3-morpholin-4-yl-phenyl)-ethylamines.

The synthesis of four (+/-)-fluorinated 1-(3-morpholin-4-yl-phenyl)-ethylamines and an enantioselective approach to these amines through reductive amination are described.

An Unusual Trifluoromethyl Elimination Reaction from the 4,4-Bis(trifluoromethyl)-5-hydroxyimidazoline Ring System.

A facile detrifluoromethylation was observed when 4,4-bis(trifluoromethyl)-5-hydroxyimidazoline 5 was treated with a variety of bases to afford the biologically interesting 4-(trifluoromethyl)imidazole analogs (9 and 10). A unique mechanism was proposed for this transformation, supported by isolating and trapping the hypothesized intermediates. Heating of 5 with Et(4)NCN in DMSO provided 19, which was clearly derived from the proposed intermediate 17. Finally, imidazole 9 was converted into the N-[2-phenyl-4-(trifluoromethyl)-1H-imidazol-5-yl]-N-methylbenzamide analogs, which were potential acyl CoA:cholesterol acyltransferase (ACAT) inhibitors.