Formulation of Isopropyl Isothiocyanate Loaded Nano Vesicles Delivery Systems: In Vitro Characterization and In Vivo Assessment

Isopropyl Isothiocyanate (IPI) is a poorly water-soluble drug used in different biological activities. So, the present work was designed to prepare and evaluate IPI loaded vesicles and evaluated for vesicle size, polydispersity index (PDI) and zeta potential, encapsulation efficiency, drug release, and drug permeation. The selected formulation was coated with chitosan and further assessed for the anti-platelet and anti-thrombotic activity. The prepared IPI vesicles (F3) exhibited a vesicle size of 298 nm ± 5.1, the zeta potential of −18.7 mV, encapsulation efficiency of 86.2 ± 5.3% and PDI of 0.33. The chitosan-coated IPI vesicles (F3C) exhibited an increased size of 379 ± 4.5 nm, a positive zeta potential of 23.5 ± 2.8 mV and encapsulation efficiency of 77.3 ± 4.1%. IPI chitosan vesicle (F3C) showed enhanced mucoadhesive property (2.7 folds) and intestinal permeation (~1.8-fold) higher than IPI vesicles (F3). There was a significant (p < 0.05) enhancement in size, muco-adhesion, and permeation flux achieved after coating with chitosan. The IPI chitosan vesicle (F3C) demonstrated an enhanced bleeding time of 525.33 ± 12.43 s, anti-thrombin activity of 59.72 ± 4.21, and inhibition of platelet aggregation 68.64 ± 3.99%, and anti-platelet activity of 99.47%. The results of the study suggest that IPI chitosan vesicles showed promising in vitro results, as well as improved anti-platelet and anti-thrombotic activity compared to pure IPI and IPI vesicles.     

缺锌对大鼠所致危害的实验研究

用缺锌饲料饲养Wister大鼠,以N-甲基-N硝基-N亚硝基胍(MNNG)作为致癌剂染毒,观察了缺锌对大鼠的危害。结果显示,实验组动物血清锌降低,脱毛、吃毛,体质量减轻,免疫力下降,前胃黏膜增生,前胃癌发生率显著高于对照;2例实验组大鼠胃腺区发生非典型增生,对照组无此种现象。提示适量锌具有保护胃黏膜、抑制肿瘤发生的作用;缺锌是导致胃癌发生率升高的危险因素。     

Systemically Injectable Enzyme‐Loaded Polyion Complex Vesicles as In Vivo Nanoreactors Functioning in Tumors

The design and construction of nanoreactors are important for biomedical applications of enzymes, but lipid‐ and polymeric‐vesicle‐based nanoreactors have some practical limitations. We have succeeded in preparing enzyme‐loaded polyion complex vesicles (PICsomes) through a facile protein‐loading method. The preservation of enzyme activity was confirmed even after cross‐linking of the PICsomes. The cross‐linked β‐galactosidase‐loaded PICsomes (β‐gal@PICsomes) selectively accumulated in the tumor tissue of mice. Moreover, a model prodrug, HMDER‐βGal, was successfully converted into a highly fluorescent product, HMDER, at the tumor site, even 4 days after administration of the β‐gal@PICsomes. Intravital confocal microscopy showed continuous production of HMDER and its distribution throughout the tumor tissues. Thus, enzyme‐loaded PICsomes are useful for prodrug activation at the tumor site and could be a versatile platform for enzyme delivery in enzyme prodrug therapy.     

Assessment of the In Vivo and In Vitro Release of Chemical Compounds from Vespa velutina

Vespa velutina has been rapidly expanding throughout Galicia since 2012. It is causing human health risks and well-known losses in the beekeeping sector. Control methods are scarce, unspecific, and ineffective. Semiochemicals are insect-derived chemicals that play a role in communication and they could be used an integrated pest management tool alternative to conventional pesticides. A previous determination of the organic chemical profile should be the first step in the study of these semiochemicals. HS-SPME in living individuals and the sting apparatus extraction followed by GC-MS spectrometry were combined to extract a possible profile of these compounds in 43 hornets from Galicia. The identified compounds were hydrocarbons, ketones, terpenes, and fatty acid, and fatty acid esters. Nonanal aldehyde appeared in important concentrations in living individuals. While pentadecane, 8-hexyl- and ethyl oleate were mainly extracted from the venom apparatus. Ketones 2-nonanone, 2-undecanone and 7-nonen-2-one, 4,8-dimethyl- were identified by both procedures, as was 1,7-Nonadiene, 4,8-dimethyl-. Some compounds were detected for the first time in V. velutina such as naphthalene, 1,6-dimethyl-4-(1-methylethyl). The chemical profile by caste was also characterized.     

EDTA滴定法测定含锌物料中氧化锌

采用氯化铵-氨水体系溶解试样,干过滤后,向移取的滤液中加入氯化钡和硫酸共沉淀铅离子,过滤分离硫酸铅沉淀,向滤液中加人抗坏血酸、氟化钾、硫代硫酸钠等掩蔽剂掩蔽少量干扰元素。在pH=5~6的乙酸-乙酸钠缓冲溶液中,以二甲酚橙为指示剂,用EDTA标准滴定溶液滴定测得结果为氧化锌、水溶性锌和镉合量,扣除由原子吸收光谱法测得的水溶性锌量和镉量,即为氧化锌量。对总氨浓度、氯化铵-氨水浓度比、溶液加入量、搅拌时间、共存离子干扰、精密度等进行了实验,建立了EDTA滴定法测定含锌物料中氧化锌物相的分析方法。实验证明,氧化锌含量在24%~83%时,方法精密度(RSD)为0.25%~0.54%,加标回收率在99%~104%,完全满足含锌物料中氧化锌的测定要求。     

返滴定法测定含镍锌物料中的锌含量

使用盐酸-硝酸-硫酸将试样溶解,并在氨性条件下过滤,沉淀分离大量共存元素,加入掩蔽剂掩蔽滤液中的干扰元素,在pH=5.5～6.0的缓冲溶液中,选用二甲酚橙作为指示剂,加入过量的EDTA标准滴定溶液,静置使之与溶液中的镍、锌等金属离子充分络合,用氯化锌标准滴定溶液滴定过量的EDTA。测得结果为锌、镉、镍合量,扣除镉、镍量,即为锌量。用来测定含镍锌物料中的锌,其结果的相对标准偏差(RSD,n=11)为0.21%～0.87%,加标回收率为99.0%～102%,满足日常检测需求。     

Vesicles in Nature and the Laboratory: Elucidation of Their Biological Properties and Synthesis of Increasingly Complex Synthetic Vesicles

The important role of vesicles in many aspects of cell function is well‐recognized, but only recently have sophisticated imaging techniques begun to reveal their ubiquity in nature. While we further our understanding of the biological properties of vesicles and their physiological functions, increasingly elegant artificial vesicles are being developed for a wide range of technological applications and basic research. Herein, we examine the state of the art of biological and synthetic vesicles and place their biological features in the context of recent synthetic developments, thus providing a unique overview of these complex and rapidly developing fields. The challenges and opportunities associated with future biological and synthetic studies of vesicles are also presented.     

Efficiency Assessment of Bacterial Cellulose on Lowering Lipid Levels In Vitro and Improving Lipid Metabolism In Vivo

Bacterial cellulose (BC) is well known as a high-performance dietary fiber. This study investigates the adsorption capacity of BC for cholesterol, sodium cholate, unsaturated oil, and heavy metal ions in vitro. Further, a hyperlipidemia mouse model was constructed to investigate the effects of BC on lipid metabolism, antioxidant levels, and intestinal microflora. The results showed that the maximum adsorption capacities of BC for cholesterol, sodium cholate, Pb²⁺ and Cr⁶⁺ were 11.910, 16.149, 238.337, 1.525 and 1.809 mg/g, respectively. Additionally, BC reduced the blood lipid levels, regulated the peroxide levels, and ameliorated the liver injury in hyperlipidemia mice. Analysis of the intestinal flora revealed that BC improved the bacterial community of intestinal microflora in hyperlipidemia mice. It was found that the abundance of Bacteroidetes was increased, while the abundance of Firmicutes and Proteobacteria was decreased at the phylum level. In addition, increased abundance of Lactobacillus and decreased abundance of Lachnospiraceae and Prevotellaceae were obtained at the genus level. These changes were supposed to be beneficial to the activities of intestinal microflora. To conclude, the findings prove the role of BC in improving lipid metabolism in hyperlipidemia mice and provide a theoretical basis for the utilization of BC in functional food.     

含二茂铁基的锌配合物的结构及其生物活性

合成了4个含二茂铁基的锌配合物[Zn(FcCOO)(phen)₂]ClO₄·FcCOOH (1)(FcCOO=二茂铁甲酸根,phen=1,10-邻菲咯啉),[Zn(FcCOO)(phen)₂]·ClO₄·H₂O (2),[Zn(FcCOO)(FcCOGly)(phen)]·C₂H₅OH (3)(FcCOGly=二茂铁甲酰化甘氨酸)和[Zn(FcCOGly)₂(phen)]·CH₃OH (4)。用X-射线单晶衍射测定了配合物的晶体结构。对4个配合物的生物活性进行了初步研究,发现配合物的抗菌活性与配合物的配位键强度及phen含量有一定的关系。     

含稀土合金锌粉的制备及性能

从酸性氯化物电解液体系电解共沉积Er-Pb-In-Zn合金锌粉，通过析氢及TAFEL极化测定，比较加入稀土后耐蚀性的变化，电解液中加入不同缓蚀剂后合金锌粉耐蚀性变化；通过循环伏安测定合金锌粉制成的电极的循环寿命；以合金锌粉为负极活性材料，组装成LR6实际电池，其放电性能与加汞电池基本相当。     

Biocompatibility Assessment of Insulating Silicone Polymer Coatings Using an in vitro Glial Scar Assay

Vapor‐deposited silicone coatings are attractive candidates for providing insulation in neuroprosthetic devices owing to their excellent resistivity, adhesion, chemical inertness and flexibility. A biocompatibility assessment of these coatings is an essential part of the materials design process, but current techniques are limited to rudimentary cell viability assays or animal muscle implantation tests. This article describes how a recently developed in vitro model of glial scar formation can be utilized to assess the biocompatibility of vapor‐deposited silicone coatings on micron‐scale wires. A multi‐cellular monolayer comprising mixed glial cells was obtained by culturing primary rat midbrain cells on poly(D ‐lysine)‐coated well plates. Stainless steel microwires were coated with two novel insulating thin film silicone polymers, namely poly(trivinyltrimethylcyclotrisiloxane) (polyV₃D₃) and poly(trivinyltrimethylcyclotrisiloxane–hexavinyldisiloxane) (polyV₃D₃–HVDS) by initiated chemical vapor deposition (iCVD). The monolayer of midbrain cells was disrupted by placing segments of coated microwires into the culture followed by immunocytochemical analysis after 7 d of implantation. Microglial proximity to the microwires was observed to correlate with the amount of fibronectin adsorbed on the coating surface; polyV₃D₃–HVDS adsorbed the least amount of fibronectin compared to both stainless steel and polyV₃D₃. Consequently, the relative number of microglia within 100 µm of the microwires was least on polyV₃D₃–HVDS coatings compared to steel and polyV₃D₃. In addition, the astrocyte reactivity on polyV₃D₃–HVDS coatings was lower compared to stainless steel and polyV₃D₃. The polyV₃D₃–HVDS coating was therefore deemed to be most biocompatible, least reactive and most preferable insulating coating for neural prosthetic devices.

     

Surface Characterization,Biocompatibility and Antifungal Efficacy of a Denture-Lining Material Containing Cnidium officinale Extracts

Herein, we investigated the surface characterization and biocompatibility of a denture-lining material containing Cnidium officinale extracts and its antifungal efficacy against Candida albicans. To achieve this, a denture-lining material containing various concentrations of C. officinale extract and a control group without C. officinale extract were prepared. The surface characterization and biocompatibility of the samples were investigated. In addition, the antifungal efficacy of the samples on C. albicans was investigated using spectrophotometric growth and a LIVE/DEAD assay. The results revealed that there was no significant difference between the biocompatibility of the experimental and control groups (p > 0.05). However, there was a significant difference between the antifungal efficiency of the denture material on C. albicans and that of the control group (p < 0.05), which was confirmed by the LIVE/DEAD assay. These results indicate the promising potential of the C. officinale extract-containing denture-lining material as an antifungal dental material.     

Design,Synthesis, and In Vitro and In Vivo Antifungal Activity of Novel Triazoles Containing Phenylethynyl Pyrazole Side Chains

A series of triazole derivatives containing phenylethynyl pyrazole moiety as side chain were designed, synthesized, and most of them exhibited good in vitro antifungal activities. Especially, compounds 5k and 6c showed excellent in vitro activities against C. albicans (MIC = 0.125, 0.0625 μg/mL), C. neoformans (MIC = 0.125, 0.0625 μg/mL), and A. fumigatus (MIC = 8.0, 4.0 μg/mL). Compound 6c also exerted superior activity to compound 5k and fluconazole in inhibiting hyphae growth of C. albicans and inhibiting drug-resistant strains of C. albicans, and it could reduce fungal burdens in mice kidney at a dosage of 1.0 mg/kg. An in vivo efficacy evaluation indicated that 6c could effectively protect mice models from C. albicans infection at doses of 0.5, 1.0, and 2.0 mg/kg. These results suggested that compound 6c deserves further investigation.     

Stealth Liposomes (PEGylated) Containing an Anticancer Drug Camptothecin: In Vitro Characterization and In Vivo Pharmacokinetic and Tissue Distribution Study

Numerous attempts to overcome the poor water solubility of cam ptothecin (CPT) by various nano drug delivery systems are described in various sources in the literature. However, the results of these approaches may be hampered by the incomplete separation of free CPT from the formulations, and this issue has not been investigated in detail. This study aimed to promote the solubility and continuous delivery of CPT by developing long-lasting liposomes using various weights (M.W. 2000 and 5000 Daltons) of the hydrophilic polymer polyethylene glycol (PEG). Conventional and PEGylated liposomes containing CPT were formulated via the lipid film hydration method (solvent evaporation) using a rotary flash evaporator after optimising various formulation parameters. The following physicochemical characteristics were investigated: surface morphology, particle size, encapsulation efficiency, in vitro release, and formulation stability. Different molecular weights of PEG were used to improve the encapsulation efficiency and particle size. The stealth liposomes prepared with PEG₅₀₀₀ were discrete in shape and with a higher encapsulation efficiency (83 ± 0.4%) and a prolonged rate of drug release (32.2% in 9 h) compared with conventional liposomes (64.8 ± 0.8% and 52.4%, respectively) and stealth liposomes containing PEG₂₀₀₀ (79.00 ± 0.4% and 45.3%, respectively). Furthermore, the stealth liposomes prepared with PEG₅₀₀₀ were highly stable at refrigeration temperature. Significant changes were observed using various pharmacokinetic parameters (mean residence time (MRT), half-life, elimination rate, volume of distribution, clearance, and area under the curve) of stealth liposomes containing PEG₂₀₀₀ and PEG₅₀₀₀ compared with conventional liposomes. The stealth liposomes prepared with PEG₅₀₀₀ showed promising results with a slow rate of release over a long period compared with conventional liposomes and liposomes prepared with PEG₂₀₀₀, with altered tissue distribution and pharmacokinetic parameters.     

Glass Microsphere‐Supported Giant Vesicles for the Observation of Self‐Reproduction of Lipid Boundaries

Growth and division experiments on phospholipid boundaries were carried out using glass microsphere‐supported phospholipid (DOPC) giant vesicles (GVs) fed with a fatty acid solution (oleic acid) at two distinct feeding rates. Both fast and slow feeding methods produced daughter GVs. Under slow feeding conditions the membrane growth process (evagination, buds, filaments) was observed in detail by fluorescence microscopy. The density difference between supported mother vesicles and newly formed daughter vesicles allowed their easy separation. Mass spectrometric analysis of the resulting mother and daughter GVs showed that the composition of both vesicle types was a mixture of original supported phospholipids and added fatty acids reflecting the total composition of amphiphiles after the feeding process. Thus, self‐reproduction of phospholipid vesicles can take place under preservation of the lipid composition but different aggregate size.     

The Role of Extracellular Vesicles in the Pathogenesis,Diagnosis, and Treatment of Osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease that affects the entire joint and has been a tremendous burden on the health care system worldwide. Although cell therapy has made significant progress in the treatment of OA and cartilage regeneration, there are still a series of problems. Recently, more and more evidence shows that extracellular vesicles (EVs) play an important role in the progression and treatment of OA. Here, we discuss that EVs from different cell sources not only participate in OA progression, but can also be used as effective tools for the diagnosis and treatment of OA. In addition, cell pretreatment strategies and EV tissue engineering play an increasingly prominent role in the field of OA treatment. This article will systematically review the latest developments in these areas. As stated above, it may provide new insights for improving OA and cartilage regeneration.     

石英粉尘肺损伤大鼠肺脏、脾脏微量元素锌、铜、镁含量的测定

为探讨石英粉尘（SiO2) 对大鼠肺脏及脾脏微量元素锌，铜，镁含量的影响作用，将雄性Wistar大鼠随机分为两组，实验结束后分别测定大鼠肺脏和脾脏微量元素锌，铜，镁含量。结果表明，SiO2组与对照组比较，脾脏，肺脏锌，镁含量下降，铜含量上升（P＜0．05）。提示SiO2能使肺脏受到损伤，并引起机体微量元素失衡，使脾脏亦受到损伤，造成机体免疫功能下降。