Functional Dysregulations in CA1 Hippocampal Networks of a 3-Hit Mouse Model of Schizophrenia

For a better translation from treatment designs of schizophrenia to clinical efficiency, there is a crucial need to refine preclinical animal models. In order to consider the multifactorial nature of the disorder, a new mouse model associating three factors (genetic susceptibility—partial deletion of the MAP6 gene, early-life stress—maternal separation, and pharmacological treatment—chronic Δ-9-tetrahydrocannabinol during adolescence) has recently been described. While this model depicts a schizophrenia-like phenotype, the neurobiological correlates remain unknown. Synaptic transmission and functional plasticity of the CA1 hippocampal region of male and female 3-hit mice were therefore investigated using electrophysiological recordings on the hippocampus slice. While basal excitatory transmission remained unaffected, NMDA receptor (NMDAr)-mediated long-term potentiation (LTP) triggered by theta-burst (TBS) but not by high-frequency (HFS) stimulation was impaired in 3-hit mice. Isolated NMDAr activation was not affected or even increased in female 3-hit mice, revealing a sexual dimorphism. Considering that the regulation of LTP is more prone to inhibitory tone if triggered by TBS than by HFS, the weaker potentiation in 3-hit mice suggests a deficiency of intrinsic GABA regulatory mechanisms. Indeed, NMDAr activation was increased by GABA_A receptor blockade in wild-type but not in 3-hit mice. This electrophysiological study highlights dysregulations of functional properties and plasticity in hippocampal networks of 3-hit mice, one of the mechanisms suspected to contribute to the pathophysiology of schizophrenia. It also shows differences between males and females, supporting the sexual dimorphism observed in the disorder. Combined with the previously reported study, the present data reinforce the face validity of the 3-hit model that will help to consider new therapeutic strategies for psychosis.     

Anti-Inflammatory Treatment with FTY720 Starting after Onset of Symptoms Reverses Synaptic Deficits in an AD Mouse Model

Therapeutic approaches providing effective medication for Alzheimer’s disease (AD) patients after disease onset are urgently needed. Previous studies in AD mouse models suggested that physical exercise or changed lifestyle can delay AD-related synaptic and memory dysfunctions when treatment started in juvenile animals long before onset of disease symptoms, while a pharmacological treatment that can reverse synaptic and memory deficits in AD mice was thus far not identified. Repurposing food and drug administration (FDA)-approved drugs for treatment of AD is a promising way to reduce the time to bring such medication into clinical practice. The sphingosine-1 phosphate analog fingolimod (FTY720) was approved recently for treatment of multiple sclerosis patients. Here, we addressed whether fingolimod rescues AD-related synaptic deficits and memory dysfunction in an amyloid precursor protein/presenilin-1 (APP/PS1) AD mouse model when medication starts after onset of symptoms (at five months). Male mice received intraperitoneal injections of fingolimod for one to two months starting at five to six months. This treatment rescued spine density as well as long-term potentiation in hippocampal cornu ammonis-1 (CA1) pyramidal neurons, that were both impaired in untreated APP/PS1 animals at six to seven months of age. Immunohistochemical analysis with markers of microgliosis (ionized calcium-binding adapter molecule 1; Iba1) and astrogliosis (glial fibrillary acid protein; GFAP) revealed that our fingolimod treatment regime strongly down regulated neuroinflammation in the hippocampus and neocortex of this AD model. These effects were accompanied by a moderate reduction of Aβ accumulation in hippocampus and neocortex. Our results suggest that fingolimod, when applied after onset of disease symptoms in an APP/PS1 mouse model, rescues synaptic pathology that is believed to underlie memory deficits in AD mice, and that this beneficial effect is mediated via anti-neuroinflammatory actions of the drug on microglia and astrocytes.     

喷雾型防晒化妆品的国际法规动态和技术监管讨论

分析了我国喷雾型防晒化妆品的发展趋势,综述了欧盟、美国、澳大利亚、韩国等国家和地区的监管动态和法规要求,对此类产品的原料使用和生产工艺、理化检验、毒理学试验、防晒功效测试、产品安全评估、使用方法和标签管理等相关技术要点进行了分析和讨论,并提出了监管建议,对喷雾型防晒化妆品在监管科学下的精细化管理进行了总结和展望。     

A Phytochemical–Halogenated Quinoline Combination Therapy Strategy for the Treatment of Pathogenic Bacteria

With the continued rise of drug‐resistant bacterial infections coupled with the current discouraging state of the antibiotic pipeline, the need for new antibacterial agents that operate through unique mechanisms compared with conventional antibiotics and work in synergy with other agents is at an all‐time high. We have discovered that gallic acid, a plant‐derived phytochemical, dramatically potentiates the antibacterial activities of several halogenated quinolines (up to 11 800‐fold potentiation against Staphylococcus aureus) against pathogenic bacteria, including drug‐resistant clinical isolates. S. aureus demonstrated the highest sensitivity towards gallic acid–halogenated quinoline combinations, including one halogenated quinoline that demonstrated potentiation of biofilm eradication activity against a methicillin‐resistant S. aureus (MRSA) clinical isolate. During our studies, we also demonstrated that these halogenated quionlines operate through an interesting metal(II) cation‐dependent mechanism and display promising mammalian cytotoxicity.     

Physicochemical study on microencapsulation of hydroxypropyl-β-cyclodextrin in dermal preparations

Objective: To investigate the effect of hydroxypropyl-β-cyclodextrin (HP-β-CD) concentration on the physicochemical properties of the sunscreen agents, namely oxybenzone (Oxy), octocrylene (Oct), and ethylhexyl-methoxy-cinnamate (Cin), in aqueous solution and cream formulations. Methods: The inclusion complexes of sunscreen agents with hydroxypropyl-β-cyclodextrin (HP-β-CD) in aqueous solution and solid phase were studied by UV-vis spectrophotmetery, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and 13C-NMR techniques. The photodegradation reaction of the sunscreen agents' molecules in lotion was explored using UV-vis spectrophotometry and high-performance liquid chromatography (HPLC). Results: The formation of the inclusion complexes was confirmed experimentally using DSC, SEM, and 13C-NMR. The results of spectrophotometric and HPLC studies have shown that the inclusion complexation with HP-β-CD has the potential to enhance the photostability of the selected sunscreen agents in lotion. HPLC results indicated that HP-β-CD has approximately increases the photostability of Oct by six- to eightfold. Moreover, the presence of HP-β-CD in lotion controlled the isomerization process of Cin to a certain degree, which was found to be a function of the amount of HP-β-CD added. Conclusions: It has been demonstrated that the photostability of the tested sunscreen agents has been enhanced upon forming inclusion complexes with HP-β-CD in lotion. The results of this study demonstrate that HP-β-CD can be utilized as photostabilizer additive for enhancing the photostability of the sunscreen agents' molecules.     

载银二氧化钛在防晒霜中的应用研究

采用溶胶凝胶法将银掺人二氧化钛中,以载银二氧化钛为原料制备抗菌防晒护肤膏,研究载银二氧化钛对护肤膏的防晒性能、色泽稳定性以及抗菌性的影响,结果表明,w（银）为1%的二氧化钛应用于防晒护肤膏中具有较好的防晒性能、抗菌性和色泽稳定性。     

茶籽油防晒功效的研究与应用

利用朗伯-比尔定律,从波长200~500 nm测定各溶液的紫外吸光度,确定最大吸收波长证明茶籽油等在250~360 nm处有很好的紫外吸收能力。把天然茶籽油、生物活性物质D按一定比例调配成最佳配方,从240~400 nm测定产品紫外吸光度,绘制、分析紫外吸收图谱。将天然茶籽油、生物活性物质D与具有物理防晒的TiO2为紫外吸收剂相结合,制成具有良好的紫外吸收效果的O/w型防晒霜,天然绿色,成本低廉,具有很大的市场开发潜力。     

The effect on taste upon the introduction of heteroatoms in sulphamates

The effect on taste of introducing a heteroatom(s) in place of a carbon atom(s) in sulphamate tastants has been examined in this work. Seventy sets of heterosulphamates and their corresponding carbon analogues (130 compounds in total) were examined. This interesting database was assembled by bringing together series of heterocompounds and suitable nonhetero analogues from the literature, by the synthesis in this work of 15 new heterosulphamates and two new carbosulphamates, which was necessary “to match up” with known carbosulphamate analogues and by making taste predictions for ten carbosulphamates which are unknown, using existing well-established structure-taste relationships (SARs). A sulphur atom replaced a carbon atom in 18 cases, either oxygen or an –OH group replaced carbon in 16 cases, and there are 29 examples where a nitrogen atom or an –NH group replaced carbon. Finally, there are six instances of a “double carbon–carbon, nitrogen–nitrogen substitution” and one of a treble carbon, nitrogen substitution. The overall picture shows that in 33 instances no change in taste was found when substitution occurred, in 29 instances sweet taste (S) was removed giving a nonsweet compound (N), and in eight instances a nonsweet material (N) became sweet (S). Replacement of oxygen by sulphur resulted in the introduction of sweetness in three cases out of four examined. Several important findings were made and a number of new structure-taste relationships have been derived for heterosulphamates.     

防晒剂在乳化体系中结晶规律及其抑制机制的研究进展

随着经济水平的发展和人民生活质量的提高,防晒产品已经成为人们日常生活中不可或缺的部分,而防晒剂结晶析出作为防晒产品的主要失稳现象越来越引起人们的重视.目前,国内对于乳液体系中防晒剂结晶现象的研究主要集中在如何开发新型包覆载体技术或优化配方体系以避免结晶的出现,而对防晒剂在乳液体系中结晶机制的研究报道十分匮乏.该文概述了防晒剂的种类和作用机理,并从晶体学的角度重点剖析了防晒剂在乳化体系中的结晶过程和抑制机制,展望了防晒产品的开发和研究的趋势,利用防晒剂结晶的抑制机制来提高防晒产品稳定性和功效性具有重要的科学意义.