Shamsi, TahirMusharraf, Syed GhulamSiddiqui, Amna JabbarKhan, Muhammad Behroz Naeem...
9页
查看更多>>摘要：RBCs membrane loses its integrity during hemoglobinopathies such as beta-thalassemia and sickle cell disease. The severity of beta-thalassemia has been historically linked to the presence of XMN polymorphism which is believed to ameliorate the severity. Here, we investigate the effect of XMN polymorphism on RBC membrane lipidome isolated from patients, using LC-MS/MS based approach. A total of 50 patients were recruited and 28 lipid species were identified in all groups after statistical analyses using volcano plot and ANOVA-SCA, and lipids with higher VIP values extracted from OPLS-DA loading plot. Alteration in lipid levels specifically the membrane lipids such as PC and fatty acids were observed. Samples with XMN polymorphism exhibited up-regulation of lipids involved in membrane stability such as cholenoic acid while PC (O-41:1) was down-regulated when compared to non-XMN samples. Additionally, HU administration to samples also had profound effect on the lipids of patients in both groups. A trend of improvement in the membrane lipids was observed in patients with XMN polymorphism. HU administration has proven to further improve the membrane integrity by upregulating certain membrane lipids in such patients. The study presents a comprehensive analysis of RBC membrane lip-idome with respect to the genetic variation and HU administration.
Pereira, Lucas S. A.Camacho, Sabrina A.Almeida, Alexandre M.Goncalves, Renato S....
11页
查看更多>>摘要：Cell membranes are the first barriers for drug binding and key for the action of photosensitizers (PS). Herein, we report on the incorporation of the PS hypericin into Langmuir monolayers of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS) to represent eukaryotic cell membranes, and 1,2-dioleoyl-sn-glycero-3-phospho(1'-rac-glycerol) (DOPG) to mimic bacterial membranes. Surface pressure (pi) vs mean molecular area (angstrom) isotherms showed a high degree of interaction (binding, penetration and relative solubilization) of hypericin into DPPC and DOPC monolayers. On the other hand, electrostatic repulsions govern the interactions with DOPG and DOPS, favoring hypericin self-aggregation, as visualized by Brewster angle microscopy (BAM). Indeed, the larger domains in BAM were consistent with the greater expansion of DOPG monolayers with incorporated hypericin, owing to stronger electrostatic repulsions. In contrast to DPPC, light-irradiation of DOPC monolayers containing hypericin induced loss of material due to hydrocarbon chain cleavage triggered by contact-dependent reactions between triplet excited state of hypericin and chain unsaturations. The mild effects noted for both irradiated DOPS and DOPG monolayers are attributed to hypericin self-aggregation, which may have decreased the singlet oxygen quantum yield (Phi O-1(2)) via self-quenching, despite the increased instability induced in the monolayers.
查看更多>>摘要：Silibinin (SIL) is a neuroprotective and amyloid aggregate inhibitor that showed therapeutic applications in preclinical studies of Alzheimer's disease (AD). Due to poor aqueous solubility free SIL is unable to reach the brain after oral administration. Therefore SIL was encapsulated in nano-liquid crystals (NLCs) to increase payload in brain using glyceryl monooleate (GMO). The NLCs were prepared through the emulsification and probe sonication method. The optimization of SIL-NLCs was done using Box-Behnken design (BBD). BBD investigated the effect of independent variable such as GMO weight, pluronics-127 (PF-127) concentration, and sonication time on critical quality attributes such as particle size and percentage drug loading (%DL) for enhancement of drug availability at targeted site. The particle size of SIL-NLCs optimized by BBD was found to be 113.2 +/- 3.3 nm particle size and 8.02 +/- 0.4% DL. The FTIR and DSC characterization of SIL-NLCs showed SIL is dispersed in the GMO matrix in the amorphous form. TEM analysis confirmed the cubical and crystal-like shape of the NLCs having particle size less than 150 nm. After single oral gavage of a 30 mg/kg dosage of SIL in Wistar rats, the pharmacokinetic investigations revealed that the amount of SIL available in plasma of animals administered with NLCs showed AUC(0-infinity) = 19.61 mu g mL(-1)h compared to free SIL group having AUC(0-infinity)= 6.72 mu g mL(-1) h (P > 0.005). Brain uptake studies showed SIL-NLCs treated groups have 2.25 mu g/g availability of SIL compared to 10.02 mu g/g for the free SIL group. The outcomes of this investigation are promising in terms of potential use of SIL-NLCs in further studies as well as using SIL for the treatment of AD.
查看更多>>摘要：ABSTR A C T Background: Non-alcoholic fatty liver disease (NAFLD) is considered to be the leading cause of liver pathologies worldwide. Accurate diagnosis and staging of NAFLD is of utmost prognostic importance. Herein, we propose the application of multiparametric MRI in whole-body fat imaging that may serve in obesity and NAFLD diagnosis as we established based on an experimental preclinical model of high-calorie diet-induced NAFLD rats.Methods and results: Sprague Dawley male rats randomly divided into control and high-fat diet (HFD) groups to develop NAFLD were used in the experiments. After 12 weeks of the feeding the animals were subjected to MRI modalities based on the Dixon mode and DWI following T2-weighted imaging. Moreover, serum TAG, liver histopathological examination and liver fatty acids analysis (GC-MS) were also performed.The qualitative analysis of DWI images revelated the decrease of signals in the liver of rats subjected to HFD. The statistical analysis of signals from the water-and fat-separated voxels on Dixon images also showed the increase of the fat tissue along with the decrease of water molecules in the liver parenchyma of obese animals. The quantitative analysis of Dixon images allowed to estimate the statistically significant changes of whole-body fat profiles in both normal and obese rats. Histological analysis of the liver tissues, serum TAG and fatty acids profile in the livers confirmed the changes in the fat profile as demonstrated in MRI studies.Conclusions: The MRI-based modalities such as DWI and Dixon method provide both qualitative and quantitative data on the whole-body fat distribution and adipose tissues in the liver parenchyma of obese rats. The results show that MRI is a promising and reliable method and has potential to be used as a non-invasive translational biomarker in NAFLD.
查看更多>>摘要：Curcumin has been incorporated for the development of new products with applicability in food, pharmaceutical and cosmetic fields in Asia, due to the traits of anti-oxidation and anti-inflammatory. In the application of food engineering, high-pressure processing (HPP) can destroy non-covalent bonds and use as a method to inactivate bacteria for extending the perseveration of food. Thus, this study focuses on a novel approach for the micro encapsulation of curcumin by the combination of ethanol injection and HPP at the room temperature for stabilizing pure curcumin in aqueous solutions and in liposome. The results revealed that the most optimal curcumin-liposome was prepared by HPP at operational pressure of 200 MPa within 5 mins holding time to obtain the minimum particle size of 281.9 nm, encapsulation efficiency of 87.25% and polydispersity index (PDI) of 0.23. Particle size could reduce to nanoscale (70.65 nm) after 0.5% addition of Tween 80, but the encapsulation efficiency spontaneously decreased to 45.05%. It is an option to produce liposome with nanosize and uniform distribution for the consideration of high drug delivery. Conclusively, HPP process could not only effectively decrease particle size and PDI of liposome but also efficiently sterilize bacteria around concentration of 10(3) CFU/g.
查看更多>>摘要：Three oxysterols (7 beta-hydroxycholesterol; 7 beta-OH, 7-ketocholesterol; 7-K and 25-hydroxycholesterol, 25-OH) differing in the site of oxidation (ring system versus chain) and kind of polar group (hydroxyl versus carbonyl) were studied in lipid raft environment using the Langmuir monolayer technique complemented with theoretical calculations. Experiments were performed for the unmodified raft system, composed of sphingomyelin (SM) and cholesterol (Chol), and in the next step the raft was modified by the incorporation of oxysterol in different proportions. In the examined three-component system (Chol:SM:oxysterol), apart from interactions between the lipid raft components, the affinity of Chol to its oxidized derivatives also plays an important role. 25-OH was found to enhance interactions between SM and Chol and thus stabilize the raft, contrary to 7 beta-OH and 7-K, which exerted the fluidizing effect as well as the destabilization of the raft. Different action of oxysterols on model raft was observed. 7 beta-OH and 7-K, which are highly potent inducers of cell death caused raft destabilization, while 25-OH, which is the least toxic of the investigated oxysterols, was found to stabilize the raft.
NSTL
Elsevier