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Stroke was always a disease that threatened human life and health worldwide. We reported the synthesis of a new type of hyaluronic acid-modified multi-walled carbon nanotube. Then, we produced hydroxysafflor yellow A-hydroxypropyl-β-cyclodextrin phospholipid complex water-in-oil nanoemulsion with hyaluronic acid-modified multi-walled carbon nanotubes and chitosan (HC@HMC) for oral treatment of an ischemic stroke. We measured the intestinal absorption and pharmacokinetics of HC@HMC in rats. We found that the intestinal absorption and the pharmacokinetic behavior of HC@HMC was superior to that of HYA. We measured intracerebral concentrations after oral administration of HC@HMC and found that more HYA crossed the blood–brain barrier (BBB) in mice. Finally, we evaluated the efficacy of HC@HMC in middle cerebral artery occlusion/reperfusion (MCAO/R)-injured mice. In MCAO/R mice, oral administration of HC@HMC demonstrated significant protection against cerebral ischemia-reperfusion injury (CIRI). Furthermore, we found HC@HMC may exert a protective effect on cerebral ischemia-reperfusion injury through the COX2/PGD2/DPs pathway. These results suggest that oral administration of HC@HMC may be a potential therapeutic strategy for the treatment of stroke.

Most of chemiluminescence (CL) substrates exhibit the flash-type light emission. So, the long-lasting CL system is always served as the crown in the field of CL-based analysis methodology. In this work, we constructed a Dox-ABEI chimeric magnetic DNA hydrogel (MDH) as a novel protease-free long-lasting CL reaction system. The functional MDH can transform flash type ABEI/H2O2/CO2+ reaction into glow-type CL system due to its block effect on delaying the diffusion rate of co-reactants, making the CL reaction gradually occur. More importantly, the functional MDH possessed the advantages of biocompatibility and controllable, and could be well-designed to incorporate different biosensing strategies. Subsequently, we established a functional MDH-based long-lasting CL immunoassay system for ultrasensitive and highly specific detection of D-Dimer and FDP. The designed CL immunoassay can detect D-Dimer and FDP down to 53.7 fg/mL and 31.6 fg/mL respectively, with a wide line rage from 100 fg/mL to 100 ng/mL, which was superior to previously reported CL biosensing strategies. Moreover, benefiting from the magnetic separation of MDH and excellent CL performance, the developed immunoassaying method was successfully applied in the detection of clinical samples, which exited a close correlation with clinical reference technology. Thus, this functional MDH was proved to be an excellent long-lasting CL system and a potential technical platform for clinical bioanalysis applications.

Gefitinib is a first-line treatment for patients with non-small-cell lung cancer (NSCLC), but acquired resistance is a major obstacle to its therapeutic efficacy, and the underlying mechanisms are not fully elucidated. Recent studies have indicated that circular RNAs play a crucial role in chemoresistance, but their expression and function in NSCLC cells with acquired resistance to gefitinib are largely unknown. In this study, we determined that circSETD3 was significantly upregulated in gefitinib-resistant NSCLC cell lines and the plasma of gefitinib-resistant NSCLC patients. circSETD3 markedly decreased the gefitinib sensitivity of NSCLC cells both in vitro and in nude mice xenografts. It could directly bind to miR-520h and lead to the upregulation of ATP-binding cassette subfamily G member 2 (ABCG2), an efflux transporter of gefitinib, resulting in a reduced intracellular gefitinib concentration. Moreover, we reported that the downregulation of serine/arginine splicing factor 1 (SRSF1) contributed to, at least in part, the increased expression of circSETD3 in NSCLC cells with acquired resistance to gefitinib. Taken together, our findings indicated that circSETD3 may serve as a prognostic biomarker and a potential therapeutic target for acquired resistance to gefitinib in NSCLC., Graphical Abstract, Wu and colleagues identified circSETD3, which could regulate acquired resistance to gefitinib in NSCLC. They characterized the SRSF1/circSETD3/miR-520h/ABCG2 axis, which decreased intracellular concentration of gefitinib after drug resistance. They also demonstrated the effect of circSETD3 on acquired resistance to gefitinib in vivo.

Stroke has always been a disease threatening human life and health worldwide. Here, we synthesized a new type of hyaluronic acid-modified multi-walled carbon nanotube. Then we prepared hydroxysafflor yellow A-hydroxypropyl-β-cyclodextrin phospholipid complex water-in-oil nanoemulsion with hyaluronic acid-modified multi-walled carbon nanotubes and chitosan (HC@HMC) for oral treatment of ischemic stroke. First, we measured the intestinal absorption and pharmacokinetics of HC@HMC in rats. We found that the intestinal absorption and the pharmacokinetic behavior of HC@HMC is better than HYA. Then we detected intracerebral concentrations after oral administration of HC@HMC and found that more HYA crossed the blood-brain barrier (BBB). Finally, we evaluated the efficacy of HC@HMC in middle cerebral artery occlusion/reperfusion (MCAO/R)-treated mice. In MCAO/R mice, oral administration of HC@HMC demonstrated a significant protection against cerebral ischemia-reperfusion injury (CIRI). And we also found HC@HMC may exert a protective effect on cerebral ischemia-reperfusion injury through COX2/PGD2/DPs pathway. These results suggest that oral administration of HC@HMC may be a new strategy for the treatment of stroke.

Background: Anti-tuberculosis drug concentrations are critical for the treatment of spinal tuberculosis. The distribution pattern of anti-tuberculosis drugs between the blood and the vertebral focus needs to be further explored. Methods: A total of 31 spinal tuberculosis patients were prospectively included and then divided into a sclerotic group (15 cases) and a non-sclerotic group (16 cases) according to their preoperative CTs. All patients were treated with 2HERZ/6H2R2Z2 chemotherapy for 4 weeks before the operation. During the operation, blood, normal vertebral bone tissue, and vertebral focus tissue were obtained, processed, and sent to the pharmacology laboratory. The concentration values of four anti-tuberculosis drugs in each sample were obtained in a pharmacology laboratory. Results: There was no significant difference in the concentrations of the four anti-tuberculosis drugs in the blood and the normal vertebral bone tissue between the two groups; however, there was a significant difference in the vertebral focus tissue. There existed a linear correlation of four anti-tuberculosis drug concentrations between the blood and the focus in the non-sclerotic bone group. Conclusions: The existence of sclerotic bone hinders the anti-tuberculosis drug distribution. In the absence of sclerotic bone in the vertebral focus, there exists a linear relationship of the four anti-tuberculosis drug concentrations between the blood and the vertebral focus of spinal tuberculosis patients.

Backgrond: Astragaloside IV (AST) and metoprolol are often used together to treat cardiovascular diseases, while the herb-drug interaction (HDI) between them is still unclear. Objective: This study investigates the effect of AST on the pharmacokinetics of metoprolol in rats and its mechanism to predict the HDI. Method: First, IC50 value of AST on nine CYP450 enzymes in human liver microsomes (HLMs) was determined by the cocktail method. We explored the effect of AST on the pharmacokinetics of metoprolol (metabolized by CYP2D6) in vivo. Twelve male SD rats were equally divided into two groups, with or without pretreatment of AST (3 mg/kg/day) for 7 days, and they received metoprolol (27 mg/kg) by oral administration. Blood samples were determined using HPLC. Finally, the mechanism of AST was explored. Results: AST exhibited a moderate inhibitory effect on CYP2D6 with IC50 value of 32.28 μM. The pharmacokinetic parameters of metoprolol were significantly altered by AST with the increase of AUC0-∞ (538.81 ± 51.41 to 1088.34 ± 86.46 μg*min/mL, P Conclusion: AST was found to increase the plasma exposure of metoprolol in rats. AST reduced the metabolism of metoprolol by inhibiting CYP2D6 activity. The HDI might enhance when metoprolol and AST will be applied in combination.

Osthol, a pharmacologically active ingredient in various traditional Chinese medicines, is predominantly metabolized by CYP2C9. It may be co-administered with other drugs which are metabolized by CYP2C9 in clinical medicine. However, CYP2C9*1/*2/*3 genotype on the pharmacokinetics of osthole and its metabolic diversity between rat and human are unclear.In this study, we investigated the effects of osthole on enzyme activity of CYP2C11/CYP2C9 in rat liver microsomes (RLMs) and human liver microsomes (HLMs), to distinguish metabolic manner of osthole in different species. Interestingly, we found that osthole inhibits the activity of CYP2C11 in a non-competitive manner in RLMs, while inhibits CYP2C9 activity in a competitive manner in pooled HLMs. Then, the effects of CYP2C9*1/*2/*3 allele on the pharmacokinetics of osthole were identified. In human CYP2C9 isoform, the Ki value of 21.93 μM (CYP2C9*1), 18.10 μM (CYP2C9*2), 13.12 μM (CYP2C9*3) indicate that there are individual differences in the inhibition of osthole on CYP2C9 activity.We investigated how the indomethacin pharmacokinetics was affected by osthole in SD rat. To estimate the area under the curve (AUC), maximum plasma concentration (

Medical laboratory technology major was set up to meet rapid development of science and medical research technology in 2013. Students majoring in medical laboratory had learnt a lot of techniques distributed among different specialized courses. But, they did not understand why they had to learn these techniques and how they were applied in a real-world research setting. In a one-month innovation experimental practice described herein, students had learnt to induce, purify and identify an unknown glycoprotein from whole cell lysate using conA-based affinity chromatography and mass spectrometry. Unlike in a traditional cookbook-style experiment, students chose a research subject on their own and did experiment using their selected variables. Over the one-month laboratory periods, students used sterile technique to cultivate cells, induced glycoprotein expression using LPS and IFN-γ, purified glycoprotein from cell lysate using agarose-conA beads, identified a glycoprotein via mass spectrometry, and confirmed the result using western blotting. At end of the practice, students were asked to evaluate their experiences via an anonymous survey. All students declared that this experimental practice was interesting and meaningful to them. The process of completing the project was to apply the learnt techniques to real-world biochemistry research, so they became aware of the importance and significance of techniques. © 2018 by The International Union of Biochemistry and Molecular Biology, 46:373-381, 2018.

Geniposide, the main medicinal ingredient of Gardenia jasminoides Ellis, is known to be a resistant agent to atherosclerosis. Some reports its mechanism against atherosclerosis remains completely unclear. Herein, we have investigated the protective effect of geniposide against atherosclerosis as well as clarified the mechanisms related with inhibiting the formation of foam cells and lowering reverse lipid transport via p38/MAPK signaling pathways. Macrophage Raw264.7 was induced by lysophosphatidic acid (LPA) to form foam cell as a cell model. ApoE-/- mice were fed with a high-fat diet for 16 weeks to cause atherosclerosis in carotid artery. After treatment with geniposide, CCK-8, oil red O stain, qRT-PCR and western blot were carried out to explore the effect of geniposide. Morphological changes, histological analyses were used to evaluate atherosclerosis in ApoE-/- mice. Geniposide significantly reduced serum total cholesterol (TC), triglyceride (TG) and LDL cholesterol levels in ApoE-/- mice compared with vehicle control. Meanwhile, geniposide dose dependently inhibited the development of atherosclerosis in ApoE-/- mice. Furthermore, geniposide observably inhibited the formation of foam cells induced by LPA, down-regulated the mRNA and protein levels of SR-A and up-regulated the mRNA and protein levels of ABCA1 or SR-B1 in vitro via inhibition of the p38MAPK and AKT signaling pathways. Our study shows that geniposide protected against atherosclerosis and inhibited the formation of foam cells by regulating the equilibrium on expression of diverse lipid transporters in cytomembrane which related with p38MAPK and AKT signaling pathways. Geniposide is a potential therapeutic drug for atherosclerosis.

Oral administration shows good tolerance in patients. Botanic anticancer drugs without serious side effects have attracted increased attention worldwide. However, oral delivery of natural anticancer drugs faces great challenges due to low solubility, gastrointestinal side effects, first-pass effects, and P-glycoprotein efflux. Here, we loaded the natural polyphenol curcumin (Cc) into natural polysaccharide-cloaked lipidic nanocarriers (Cc@CLNs) to improve the efficacy in small-cell lung cancer (SCLC) associated with oral administration. Compared to other nanoformulations, Cc@CLNs have advantages of simple operation, easy scale-up, low cost, and high safety. Cc@CLNs improve bioavailability by inducing synergistic effects (efficient cell membrane penetration, inherent muco-adhesiveness, resistance to pepsin and trypsin degradation, promoted dissolution, enhanced epithelia/M cellular uptake and inhibition of efflux transporters) and countering the tendency of nanocarriers to aggregate and fuse, which limit lipid-based nanosystems. In this study, we first evaluated the oral bioavailability of Cc@CLNs in rats and their efficacy in H446 tumor-bearing mice. The oral bioavailability increased by 8.94-fold, and the tumor growth inhibition rate doubled compared to that achieved with free Cc. We investigated the action of Cc against SCLC stem cells, and Cc@CLNs greatly enhanced this action. The expression of CD133 and ABCG2 in the Cc@CLNs group decreased by 38.05% and 32.57%, respectively, compared to the respective expression levels in the control.

Diffuse axonal injury (DAI) is a prevalent and serious brain injury with significant morbidity and disability. However, the underlying pathogenesis of DAI remains largely unclear, and there are still no objective laboratory-based tests available for clinicians to make an early diagnosis of DAI. An integrated analysis of metabolomic data and proteomic data may be useful to identify all of the molecular mechanisms of DAI and novel potential biomarkers. Therefore, we established a rat model of DAI, and applied an integrated UPLC-Q-TOF/MS-based metabolomics and isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis to obtain unbiased profiling data. Differential analysis identified 34 metabolites and 43 proteins in rat plasma of the injury group. Two metabolites (acetone and 4-Hydroxybenzaldehyde) and two proteins (Alpha-1-antiproteinase and Alpha-1-acid glycoprotein) were identified as potential biomarkers for DAI, and all may play important roles in the pathogenesis of DAI. Our study demonstrated the feasibility of integrated metabolomics and proteomics method to uncover the underlying molecular mechanisms of DAI, and may help provide clinicians with some novel diagnostic biomarkers and therapeutic targets.

Medical laboratory technology major was set up to meet rapid development of science and medical research technology in 2013. Students majoring in medical laboratory had learnt a lot of techniques distributed among different specialized courses. But, they did not understand why they had to learn these techniques and how they were applied in a real-world research setting. In a one-month innovation experimental practice described herein, students had learnt to induce, purify and identify an unknown glycoprotein from whole cell lysate using conA-based affinity chromatography and mass spectrometry. Unlike in a traditional cookbook-style experiment, students chose a research subject on their own and did experiment using their selected variables. Over the one-month laboratory periods, students used sterile technique to cultivate cells, induced glycoprotein expression using LPS and IFN-γ, purified glycoprotein from cell lysate using agarose-conA beads, identified a glycoprotein via mass spectrometry, and confirmed the result using western blotting. At end of the practice, students were asked to evaluate their experiences via an anonymous survey. All students declared that this experimental practice was interesting and meaningful to them. The process of completing the project was to apply the learnt techniques to real-world biochemistry research, so they became aware of the importance and significance of techniques. © 2018 by The International Union of Biochemistry and Molecular Biology, 46:373-381, 2018.

The gastric pathogen Helicobacter pylori is known to activate epithelial cell signaling pathways that regulate numerous inflammatory response genes. The aim of this study was to elucidate the pathway leading to extracellular signal-regulated kinase (ERK) 1/2 phosphorylation in H. pylori-infected AGS gastric epithelial cells. We find that H. pylori, via activation of the epidermal growth factor (EGF) receptor activates the small GTP-binding protein Ras, which in turn, mediates ERK1/2 phosphorylation. cag+ strains of H. pylori are able to induce greater EGF receptor activation than cag- strains, and studies with isogenic mutants indicate that an intact type IV bacterial secretion system is required for this effect. Blockade of EGF receptor activation using tyrphostin AG1478 prevents H. pylori-mediated Ras activation, inhibits ERK1/2 phosphorylation, and substantially decreases interleukin-8 gene expression and protein production. Investigations into the mechanism of EGF receptor activation, using heparin, a metalloproteinase inhibitor and neutralizing antibodies reveal that H. pylori transactivates the EGF receptor via activation of the endogenous ligand heparin-binding EGF-like growth factor. Transactivation of gastric epithelial cell EGF receptors may be instrumental in regulating both proliferative and inflammatory responses induced by cag+ H. pylori infection.

The purpose of this study was to develop and evaluate the supermolecular evodiamine (EVO) loaded water-in-oil nanoemulsions containing brucea javanica oil (NESEB) with enhanced physicochemical and biological characteristics. NESEB was fabricated by applying supermolecular phytosome nanotechnology and nanoemulsification technology together, in addition to using synergistic plant essential oil as a basic composition. Preferred physicochemical and biological characteristics of NESEB were investigated and compared with free EVO and other nanoemulsive EVO carriers. The possible explanations for improved absorption and bioavailability were put forward here. NESEB had high absorption and bioavailability, for example: the absorption rate constants and permeabilities of NESEB in different intestinal segments were 3.65-6.76 times that of free EVO; the relative bioavailability of NESEB to free EVO was 846.97%. NESEB markedly improved the oral bioavailability of EVO, which was most likely due to the increased gastrointestinal absorption. The development of nanoemulsion-based supermolecular EVO nanocarriers provides valuable tactics in insoluble natural antitumor drug delivering.

Amanita is one of cosmopolitan genera of basidiomycetes. This genus contains some of the most poisonous toadstools, as well as several species of the most favorite edible mushrooms. In this paper, Fourier transform infrared spectroscopy was used for obtaining vibrational spectra of the fruiting bodies of wild growing Amanita mushrooms. The results show that the mushrooms exhibit characteristic spectra, whose strong absorption bands appear at about 1655, 1076, and 1040 cm -1 . The vibrational spectra indicate that the main compositions of the Amanita mushrooms are proteins and polysaccharides. The observed spectral differences might be used to discriminate different species of Amanita . It is showed that FTIR spectroscopic method is a valuable tool for rapid and nondestructive identification of Amanita mushrooms.

The basidiomycetes Thelephora ganbajun Zang and Termitomyces albuminosus (Berk.) Heim are two of the most favorite edible mushrooms in Yunnan Province, Southwest of China. In this paper, Fourier transform infrared speciroseopy (FTIR) was used to characterize the fruiting bodies of the two wild growing edible mushrooms. The results show that each mushroom has its characteristic infrared spectrum, in which the major peaks are attributed to proteins and polysaccharides. The spectra indicate that the poiysaccharides of the two mushrooms contain, both. α- and β-glycosidic linkage. A characteristic band of Thelephora ganbajun is an obvious band at about 1763 cm -1 , which indicates that the mushroom contain oil. Differences are observed in the spectra of different parts of the fruiting body of Termitomyces albuminosus . According to the differences of the characteristic spectra peaks and absorbance ratios, the different parts of mushroom can be discriminated. The results suggest that the different species of mushrooms might be identified by the vibrational spectral features of the different parts of the fruiting bodies of mushrooms.

Vancomycin, a glycopeptide antibiotic against Gram-positive bacteria, works by binding tightly to peptidoglycan strands in the bacterial cell wall that terminates in D-Ala-D-Ala and blocks the transglycosylation of nascent peptidoglycan strands [1]. Vancomycin resistant cells have replaced the normal D-Ala-D-Ala peptidoglycan termini with D-AlaDLactate termini that are no longer recognized by vancomycin [2,3]. We hypothesize that by using D-Ala-D-lactate as a probe for screening “one-bead, one-compound” combinatorial chemical libraries [4,5], antibacterial agents that inhibit vancomycin resistant bacteria can be isolated.

In this paper, Fourier transform infrared spectroscopy (FTIR) was used to study the fruiting bodies of six species of wild growing edible mushrooms belonging to Boletes of Basidiomycetes. The results show that each mushroom has its characteristic infrared spectrum, in which the major peaks are attributed to proteins and polysaccharides. The spectra indicate that both α-glucans and β-glucans exist in the polysaccharides of mushrooms. According to the differences of their characteristic spectra peaks and absorbance ratios, the different species of Boletes can be identified. The region between 750 and 1200 cm -1 could serve as fingerprints to discriminate mushrooms. A new identification method of mushrooms may be based on the characteristic vibrational spectra and chemical information provided by FTIR.