New Quality Evaluation of Qizhi Xiangfu Pills Based on Fingerprint with Chemometric Analysis and Quantitative Analysis of Multi-Components by Single Marker.

Qizhi Xiangfu Pills (QZXFPs) is one of the most commonly used traditional Chinese medicine preparations for the treatment of dysmenorrhea, but the existing quality evaluation standards have certain shortcomings and deficiencies. An effective and scientific quality evaluation method plays a vital role in medication safety. In this study, fingerprint combined with chemometric analysis and quantitative analysis of multi-components by a single marker (QAMS) method was used to comprehensively evaluate the quality of QZXFPs. The fingerprints of 28 batches samples were established and 23 common peaks were distinguished, of which 7 peaks were identified as albiflorin, paeoniflorin, baicalin, ligustilide, cyperotundone, nootkatone and α-cyperone. The content of these seven active ingredients was determined simultaneously by the QAMS method and there was no significantly different between QAMS and the external standard method. Additionally, similarity analysis, hierarchical cluster analysis, principal component analysis and orthogonal partial least squares discrimination analysis were applied for classifying the 28 batches of samples, and to find the main components causing the quality differences between different batches. In conclusion, the established method can comprehensively evaluate the consistency of quality between different batches and provide a reference for formulation quality evaluation to ensure safe and effective application of QZXFPs.

Celastrol ameliorates energy metabolism dysfunction of hypertensive rats by dilating vessels to improve hemodynamics.

The impact of hypertension on tissue and organ damage is mediated through its influence on the structure and function of blood vessels. This study aimed to examine the potential of celastrol, a bioactive compound derived from Tripterygium wilfordii Hook F, in mitigating hypertension-induced energy metabolism disorder and enhancing blood perfusion and vasodilation. In order to investigate this phenomenon, we conducted in vivo experiments on renovascular hypertensive rats, employing indirect calorimetry to measure energy metabolism and laser speckle contrast imaging to evaluate hemodynamics. In vitro, we assessed the vasodilatory effects of celastrol on the basilar artery and superior mesenteric artery of rats using the Multi Wires Myograph System. Furthermore, we conducted preliminary investigations to elucidate the underlying mechanism. Moreover, administration of celastrol at doses of 1 and 2 mg/kg yielded a notable enhancement in blood flow ranging from 6 to 31% across different cerebral and mesenteric vessels in hypertensive rats. Furthermore, celastrol demonstrated a concentration-dependent (1 × 10-7 to 1 × 10-5 M) arterial dilation, independent of endothelial function. This vasodilatory effect could potentially be attributed to the inhibition of Ca2+ channels on vascular smooth muscle cells induced by celastrol. These findings imply that celastrol has the potential to ameliorate hemodynamics through vasodilation, thereby alleviating energy metabolism dysfunctions in hypertensive rats. Consequently, celastrol may hold promise as a novel therapeutic agent for the treatment of hypertension.

Identification of Different Varieties of Oil Peony Seeds Combining ICP-MS with Chemometrics and Assessment of Associated Health Risk.

Peony seed is an excellent oil crop, and peony seed oil is rich in unsaturated fatty acids needed by the human body. In this study, inductively coupled plasma mass spectrometry (ICP-MS), fingerprint, and chemometrics, the correlation between the content of inorganic elements in oil peony seeds, their origins, and varieties were investigated. Meanwhile, estimated daily intake (EDI), target hazard quotient (THQ), hazard index (HI), and carcinogenic risks (CR) were combined to evaluate the comprehensive health risks of heavy metals in peony seed oil. The results showed that the difference in the content of inorganic elements could identify the varieties of oil peony seeds. Sr, K, Ca, V, Al, Fe, Cu, Ba, As, Ga, Co, and Rb were the characteristic inorganic elements that played a role in identification. In addition, The THQs and HIs (< 1) for non-carcinogenic elements indicated no risk. The CRs indicated that the carcinogenic harm was negligible. The study concluded that three varieties of peony seed oil would not pose any health hazard. It provided an effective comprehensive method for the identification of oil peony seeds and predicted the potential health risks of edible peony seed oil, providing a reference for the development and consumption of peony seed oil food.

M2 Macrophage Hybrid Membrane-Camouflaged Targeted Biomimetic Nanosomes to Reprogram Inflammatory Microenvironment for Enhanced Enzyme-Thermo-Immunotherapy.

Excessive inflammatory reactions caused by uric acid deposition are the key factor leading to gout. However, clinical medications cannot simultaneously remove uric acid and eliminate inflammation. An M2 macrophage-erythrocyte hybrid membrane-camouflaged biomimetic nanosized liposome (USM[H]L) is engineered to deliver targeted self-cascading bienzymes and immunomodulators to reprogram the inflammatory microenvironment in gouty rats. The cell-membrane-coating endow nanosomes with good immune escape and lysosomal escape to achieve long circulation time and intracellular retention times. After being uptaken by inflammatory cells, synergistic enzyme-thermo-immunotherapies are achieved: uricase and nanozyme degraded uric acid and hydrogen peroxide, respectively; bienzymes improved the catalytic abilities of each other; nanozyme produced photothermal effects; and methotrexate has immunomodulatory and anti-inflammatory effects. The uric acid levels markedly decrease, and ankle swelling and claw curling are effectively alleviated. The levels of inflammatory cytokines and ROS decrease, while the anti-inflammatory cytokine levels increase. Proinflammatory M1 macrophages are reprogrammed to the anti-inflammatory M2 phenotype. Notably, the IgG and IgM levels in USM[H]L-treated rats decrease substantially, while uricase-treated rats show high immunogenicity. Proteomic analysis show that there are 898 downregulated and 725 upregulated differentially expressed proteins in USM[H]L-treated rats. The protein-protein interaction network indicates that the signaling pathways include the spliceosome, ribosome, purine metabolism, etc.

Nanoemulsions of Hydroxysafflor Yellow A for Enhancing Physicochemical and In Vivo Performance.

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-ß-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.

An Evaluation of Different Digestion Methods for the Quantitation of Inorganic Elements in Human Hair Using ICP-MS.

The inorganic elements have unique properties in biochemical processes in humans. An increasing number of pathologies have been associated with essential element ions, such as lead, mercury, and cadmium. Hair has become an attractive clinical specimen for studying the longitudinal exposure to elements from the external environment. Inductively coupled plasma-mass spectrometry (ICP-MS) coupled with nitric acid (HNO3) digestion is the most common approach for determining inorganic elements from human hair. This study aims to optimize the digestion method for the absolute quantitation of 52 elements using ICP-MS, for a large cohort study in human hair. Five different HNO3 (65%) digestion methods were investigated and evaluated for their internal standard solution stability, reproducibility, element coverage, and standard solution recovery efficiency, namely, room temperature for 24 h (RT), 90°C for 4 h (T90), ultrasonic-assisted digestion (UltraS), programmed digestion of microwave digestion (MicroD), and ordinary microwave oven digestion (O-MicroD). Our results demonstrated that O-MicroD, MicroD, and RT were the best performing digestion methods for coefficient of variation (CV) scores, coverage, and recovery efficiency, respectively. In particular, the O-MicroD method detected multiple elements in a small quantity of hair (3 mg), with minimum nitric acid usage (200 µl) and a short digestion time (30 min). The O-MicroD method had excellent reproducibility, as demonstrated by a continuous thousand injections of hair samples with three internal standards (CV: 103Rh = 3.59%, 115In = 3.61%, and 209Bi = 6.31%). Future studies of the elemental content of hair should carefully select their digestion method to meet the primary purpose of their study.

The Distribution Pattern of First-Line Anti-Tuberculosis Drug Concentrations between the Blood and the Vertebral Focus of Spinal Tuberculosis Patients.

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.

Effects of Astragaloside IV on the Pharmacokinetics of Metoprolol in Rats and its Mechanism.

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<0.05) and Cmax (6.21 ± 0.56 to 8.34 ± 0.87 µg/ml, P<0.05). The investigation of the mechanism showed AST to be an irreversible inhibitor of CYP2D6 with KI value of 2.9 µM and Kinact of 0.018 min-1, respectively. 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.

Comparative Pharmacokinetic Study of Hesperetin after Oral Administration in Normal and Hyperuricemia Rats by UPLC-MS/MS.

BACKGROUND: Hesperetin has antihyperuricemia activity, and the pharmacokinetic profiles of hesperetin may be altered by hyperuricemia. This study aimed to develop a highly sensitive and specific method for the determination of hesperetin in normal and hyperuricemia rats, and to compare pharmacokinetic profiles of hesperetin after oral administration between normal and hyperuricemia rats. METHODS: Sprague-Dawley (SD) rats were randomly divided into one normal group (group A) and four hyperuricemia groups (group B, C, D, and E). Groups A, B, C, and D received a single dose (9-81 mg/kg) of hesperetin on Day 28, respectively, while group E received multiple doses (27 mg/kg) of hesperetin once daily for 28 days. Blood samples were collected at 10 different time points post-dose, and hesperetin was determined by Ultra-high Performance Liquid Chromatography- tandem Mass Spectrometric (UPLC-MS/MS). RESULTS: Compared with normal condition of group A, hyperuricemia of group C induced 48.19% and 19.57% decreases in Cmax and CL/F, and resulted in 58.25% and 19.48% increases in Tmax and AUC0-t for hesperetin, respectively. After 28 days of hesperitin treatment, Cmax of group E was significantly elevated than that of group C (p < 0.05). Hesperetin exhibited nonlinear pharmacokinetic properties in the range of 9-81 mg/kg in hyperuricemia rats. CONCLUSION: The pharmacokinetic parameters of hesperetin in hyperuricemia rats were reported for the first time. Intestinal injury may be ameliorated by hesperetin in hyperuricemia rats after 28 days' treatment. These findings could provide more beneficial information to the mechanism and clinical applications of hesperetin.

Novel Protease-Free Long-Lasting Chemiluminescence System Based on the Dox-ABEI Chimeric Magnetic DNA Hydrogel for Ultrasensitive Immunoassay.

Most of chemiluminescence (CL) substrates exhibit the flash-type light emission. Therefore, the long-lasting CL system is always 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 a glow-type CL system because of 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 controllability 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 fibrin degradation products (FDPs). The designed CL immunoassay can detect d-dimer and FDP down to 53.7 and 31.6 fg/mL, respectively, with a wide line ranging from 100 fg/mL to 100 ng/mL, which was superior to the 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 showed a close correlation with clinical reference technology. Thus, this functional MDH proved to be an excellent long-lasting CL system and a potential technical platform for clinical bioanalysis applications.

circSETD3 Contributes to Acquired Resistance to Gefitinib in Non-Small-Cell Lung Cancer by Targeting the miR-520h/ABCG2 Pathway.

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.

Oral administration of natural polyphenol-loaded natural polysaccharide-cloaked lipidic nanocarriers to improve efficacy against small-cell lung cancer.

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.

Osthole inhibited the activity of CYP2C9 in human liver microsomes and influenced indomethacin pharmacokinetics in rats.

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 (Cmax) and apparent clearance (CL/F), indomethacin (10 mg/kg) was given orally combined with osthole (20 mg/kg) in adult SD rat. We found the value of PK on indomethacin, such as the AUC0-∞, was from 176.40 ± 17.29 to 173.74 ± 27.69 µg/ml h-1, Cmax from 9.02 ± 1.24 to 9.89 ± 0.82 µg/ml and CL/F from 0.11 ± 0.01 to 0.12 ± 0.04 mg/kg/h which were unsignificantly changed compared with the control groups. However, the Tmax was prolonged from 2.00 ± 0.00 h to 7.33 ± 1.15 h, and T1/2 increased from 8.38 ± 2.30 h to 11.37 ± 2.11 h. These results indicate that osthole could potentially affect the metabolism of indomethacin in vivo.

Geniposide against atherosclerosis by inhibiting the formation of foam cell and lowering reverse lipid transport via p38/MAPK signaling pathways.

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.

Integrated Proteomics and Metabolomic Analyses of Plasma Injury Biomarkers in a Serious Brain Trauma Model in Rats.

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.

Identification of an unknown glycoprotein from whole cell lysate using conA and mass spectrometry.

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.

[Pharmacokinetics Study on Curcumin Hydroxypropyl-ß-Cyclodextrin Phospholipid Complex in Rats].

OBJECTIVE: To compare the in vivo pharmacokinetics of curcumin hydroxypropyl-ß-cyclodextrin phospholipid complex, curcumin hydroxypropyl-ß-cyclodextrin and curcumin phospholipid complex, and to discuss the advantage of hydroxypropyl-ß-cyclodextrin phospholipid complex as carrier. METHODS: Drawing blood after SD rats were oral administered with the above preparations and free drug at 50 mg/kg( corresponding to curcumin) , and the blood concentration were determined by HPLC. RESULTS: The AUC0-∞ of curcumin hydroxypropyl-ß-cyclodextrin phospholipid complex was(1 126. 20 ± 323. 24) g/(L . h), which was 5. 89, 1. 49 and 1. 17 times as curcumin (191. 08 ± 43. 27) µg/( L . h), curcumin phospholipid complex(754. 93 ± 55. 33) µg/(L . h), curcumin hydroxypropyl-ß- cyclodextrin(961. 21 ± 253. 65) µg/(L . h). CONCLUSION: The curcumin hydroxypropyl-ß-cyclodextrin phospholipid complex has a better absorption property than curcumin phospholipid complex and curcumin hydroxypropyl-ß-cyclodextrin, which is more beneficial to improve the bioavailability.

Supermolecular evodiamine loaded water-in-oil nanoemulsions: enhanced physicochemical and biological characteristics.

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.

The mucin-type glycosylating enzyme polypeptide N-acetylgalactosaminyltransferase 14 promotes the migration of ovarian cancer by modifying mucin 13.

A high expression of O-glycosylated proteins is one of the prominent characteristics of ovarian carcinoma cells associated with cell migration, which would be attributed to the upregulated expression of glycosyltransferases. Therefore, elucidating glycosyltransferases and their substrates may improve our understanding of their roles in tumor metastasis. In the present study, we reported that knockdown of polypeptide N-acetylgalactosaminyltransferase 14 (GALNT14) by small interfering RNA significantly suppressed the cell migration and altered cellular morphology. Immunoprecipitation and western blot analyses indicated that GALNT14 contributed to the glycosylation of transmembrane mucin 13 (MUC13), which was significantly higher in ovarian cancer cells compared with the normal/benign ovary tissues. Furthermore, interleukin-8 (IL-8), which could regulate the migration ability of epithelial ovarian cancer (EOC) cells, had no remarkable effect on the expression of GALNT14 and the tumor-associated carbohydrate epitope Tn antigen. In addition, extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor modulated the expression levels of GALNT14. Our findings provide evidence that GALNT14 may contribute to ovarian carcinogenesis through aberrant glycosylation of MUC13, but not through the IL-8 pathway. These data provide novel insights into understanding the function of MUC13 on neoplasm metastasis and may aid in the development of new anticancer drugs for EOC.

A correlation between altered O-GlcNAcylation, migration and with changes in E-cadherin levels in ovarian cancer cells.

O-GlcNAcylation is a dynamic and reversible posttranslational modification of nuclear and cytoplasmic proteins. In recent years, the roles of O-GlcNAcylation in several human malignant tumors have been investigated, and O-GlcNAcylation was found to be linked to cellular features relevant to metastasis. In this study, we modeled four diverse ovarian cancer cells and investigated the effects of O-GlcNAcylation on ovarian cancer cell migration. We found that total O-GlcNAcylation level was elevated in HO-8910PM cells compared to OVCAR3 cells. Additionally, through altering the total O-GlcNAcylation level by OGT silencing or OGA inhibition, we found that the migration of OVCAR3 cells was dramatically enhanced by PUGNAc and Thiamet G treatment, and the migration ability of HO-8910PM cells was significantly inhibited by OGT silencing. Furthermore, we also found that the expression of E-cadherin, an O-GlcNAcylated protein in ovarian cancer cells, was reduced by OGA inhibition in OVCAR3 cells and elevated by OGT silencing in HO-8910PM cells. These results indicate that O-GlcNAcylation could enhance ovarian cancer cell migration and decrease the expression of E-cadherin. Our studies also suggest that O-GlcNAcylation might become another potential target for the therapy of ovarian cancer.