摘要：The microbiota-gut-brain axis(MGBA)has emerged as a key prospect in the bidirectional communication between two major organ systems:the brain and the *** between the two organ systems allows the body to function without disease,whereas dysbiosis has long-standing evidence of etiopathological *** most common communication paths are the microbial release of metabolites,soluble neurotransmitters,and immune ***,each pathway is intertwined with a complex *** the emergence of in vitro models and the popularity of three-dimensional(3D)cultures and Transwells,engineering has become easier for the scientific understanding of neurodegenerative *** paper briefly retraces the possible communication pathways between the gut microbiome and the *** further elaborates on three major diseases:autism spectrum disorder,Parkinson’s disease,and Alzheimer’s disease,which are prevalent in children and the *** diseases also decrease patients’quality of ***,understanding them more deeply with respect to current advances in in vitro modeling is crucial for understanding the *** of MGBA in the laboratory uses many molecular technologies and biomaterial *** and organoids provide a more realistic picture of the cell and tissue structure than *** them with the Transwell system offers the advantage of compartmentalizing the two systems(apical and basal)while allowing physical and chemical cues between ***-edge technologies,such as bioprinting and microfluidic chips,might be the future of in vitro modeling,as they provide dynamicity.

摘要：Gatifloxacin eye drops are frequently used in eye *** such formulations have a major drawback *** duration of action and usually require 4e6 times installations daily.A chitosan coated niosomal formulation of gatifloxain was purposed to show a longer retention time on eyes and subsequent reduction in dosing *** were prepared by solvent injection method using cholesterol and *** extensive optimization of formulation was done using different ratios of cholesterol,Span-60 and drug,revealed NS60-5(cholesterol:span-6050:50 and drug content of 20 mg)to be the optimized niosome ***60-5 had shown a highest entrapment efficiency of 64.9±0.66%with particle size 213.2±1.5 nm and zeta potential
34.7±2.2 *** niosomes were also coated with different concentrations of chitosan and *** studies had revealed that optimized niosomes(86.77±1.31%)had increased the transcorneal permeation of Gatifloxacin more than two fold than simple drug solution(37.19±1.1%).Longer retention potential of the coated niosomes was further verified by fluorescence *** revealed that simple dye solution got easily washed out with in 6 *** uncoated niosomes(NS60-5)showed a longer retention(more than 6 h),which was further enhanced in case of coated niosomes ***60-1(more than 12 h).Antimicrobial studies had shown the better efficacy of CNS60-1(zone of inhibition)when compared to marketed *** final chitosan formulation was found to have shown better ocular tolerability as demonstrated by corneal hydration test histopathology investigations.

摘要：Objective:Oral slow and sustained release drug delivery system can release their drug content with a controlled manner,producing a desirable blood serum level,reduction in drug toxicity and improving the patient compliance by prolonging dosing *** major drawback of orally administered drug like diltiazem as a calcium channel blocker for the treatment of angina pectoris,arrhythmia and *** has higher aqueous solubility and shorter elimination ***:To overcome these drawbacks associated with diltiazem,an attempt has been made to develop a sustained release dosage form of diltiazem embedded alginate microbeads by ionotropic gelation technique employing various concentrations of polymer and keeping the drug concentration ***:The beads were characterized for its particle size,drug content and in vitro release studies. The results revealed that the surface adhering drug was found to release immediately and a steady state of release was obtained up to 12 h from all the *** results indicated there was an inverse relationship between the concentration of alginate and drug *** drug release was found to follow non-fickian diffusion obeying first order ***:The developed alginate microbeads offered a sustained release of diltiazem. Hence,the formulated microbeads were found to be potential,cost effective,possess satisfactory in vitro release studies.

摘要：Design and development of efficient non-viral gene delivery systems is critical to overcome various barriers for effective intracellular gene *** new spermine-based protonatable surfactants were designed,synthesized and evaluated as non-viral pH-sensitive gene *** carriers formed stable complexes with plasmid DNA at an N/P ratio as low as *** sizes of the carrier/pDNA nanoparticles (N/P = 12) were in the range of 90–130 nm,smaller than that of Lipofectamine2000/pDNA *** pDNA nanoparticles of the carriers exhibited substantially increased hemolysis when pH decreased from 7.4 to *** DNA nanoparticles had low cytotocixity,similar to that of Lipofectamine-2000/pDNA *** pH-sensitive gene carriers with no helper lipids resulted in much higher intracellular transfection and gene expression in U87 cells than Lipofectamine-2000.[N,N′-Bis(oleoylcysteinyl)(β-alanyl-α-lysyl)]-spermine monoamide (SKACO) resulted in the highest luciferase transfection efficiency,more than 400 times higher than that of Lipofectamine-2000,and GFP expression in 71% of transfected U87 *** was identified as a promising lead carrier for efficient gene *** spermine-based pH-sensitive amphiphilic carriers have a potential to be further developed as efficient non-viral multifunctional gene delivery systems.

摘要：The present work deals with the development of controlled release tablets of salbutamol sulphate(SS)using graft copolymers of methyl methacrylate(St-g-PMMA and Ast-g-PMMA)on starch and acetylated *** were evaluated for physical characteristics like hardness,friability,drug release,drug content and weight variations,which fulfilled all the official requirements of tablet dosage *** release rates from formulated matrix tablets were studied at SGF(pH 1.2)followed by SIF(pH 6.8).Drug release from the graft copolymer based tablets was found to be sustained upto the 14 h with>75%drug *** in-vitro release study showed that the graft copolymer based matrix formulations(F3&F4)exhibited highest correlation value(r2)for higuchi kinetic model and Korsmeyer's model with n values between 0.61 and 0.67 proved that release mechanisms were governed by both diffusion and erosion *** was no significant difference in the pharmacokinetic parameters(tmax,Cmax,AUC,Ke,and t1/2)of the graft copolymers matrices and HPMC K100M matrix tablets,indicating their comparable sustained release *** potential of graft copolymers to sustain the drug release is well supported by in-vivo pharmacokinetic studies and their adequate physicochemical properties make them promising excipients for controlled drug delivery system.

摘要：与心律不齐联系的客观反常 QT 延伸在糖尿病的病人被认为主要心脏的电的混乱和死亡的一个重要预言者。为糖尿病的 QT 延伸的精确离子的机制仍然保持不清楚。现在的学习被设计在糖尿病的兔子心分析室的极化和内在的离子的机制的变化。方法糖尿病被 alloxan 的单个注射导致(145mg/kg， iv ) 。在糖尿病(10 个星期) 的发展以后， ECG 被测量。整个房间的补丁夹钳技术被使用记录行动潜力持续时间(APD50， APD90 ) ，慢慢地激活的向外修正的钾电流(Iks ) ， L 类型钙水流(Ica-L ) 和里面的修正钾电流(IK1 ) 。室的 myocytes 的行动潜力持续时间(APD50 和 APD90 ) 显然是的结果从 271.5 32.3 ms 延长了并且 347.8 ??  ? 洠瑩 ' 覞湏硺 L 污 ??????? 祭景扩楲獬 ???????? 吗？？

摘要：Purpose:Venlafaxine hydrochloride sustained release formulation increases patient compliance by reducing frequency of administration and it also reduces side effects like nausea and vomiting. Hence the objective of present investigation was to develop triple layer sustained release tablets of venlafaxine HCl using xanthan gum or polyethylene oxide. Methods:The venlafaxine HCl 150 mg sustained release tablets were prepared by wet granulation technique where drug was incorporated in middle layer with part of polymer. The barrier layers were composed of remaining polymer and other excipients. The granules and tablets were characterised. Optimized batches were also tested for drug release at different pH and in presence of ethanol, for kinetics of drug release and for water uptake/swelling. Results: Preliminary trials of monolayer tablet showed burst release due to high dose and solubility of venlafaxine HCl and hence triple layer tablets were developed. Granules of middle layer exhibited good flow properties. The comparative drug release to Effexor? XR capsule 150 mg could be achieved by modulating the concentration of polymer and diluents in middle layer as well as in barrier layers. Higher amount of polyethylene oxide was required as compared to xanthan gum which may be due to high water uptake and poor gel strength of polyethylene oxide. The optimized formulations showed pH independent drug release as well as ethanol had no effect on drug release. Effexor? XR capsule and optimized batches followed Weibull kinetics for drug release. The radar diagrams showed the comparable drug release to innovator in both the optimized formulations but point to point correlation was observed in batch with xanthan gum. Conclusion: The layered matrix tablets formulated successfully using hydrophilic polymers, xanthan gum or polyethylene oxide, to sustain the release of highly soluble drug like venlafaxine HCl.

摘要：Microbial cell factories (MCFs) are typical and widely used platforms in biomanufacturing for designing and constructingsynthesis pathways of target compounds in microorganisms. In MCFs, transporter engineering is especially significant forimproving the biomanufacturing efficiency and capacity through enhancing substrate absorption, promoting intracellular masstransfer of intermediate metabolites, and improving transmembrane export of target products. This review discusses thecurrent methods and strategies of mining and characterizing suitable transporters and presents the cases of transporterengineering in the production of various chemicals in MCFs.

摘要：背景：氨基吡啶亚乙基双磷酸甜菜碱（2-（2-aminopyrimidinio）ethylidene-1,1-bisphosphonic acid betaine,ISA）是一种新近人工合成的效力极强的双磷酸酯,将其用纳米粒包裹后通过巨噬细胞的吞噬作用而导入细胞,可以达到选择性清除巨噬细胞的目的。目的：拟验证纳米粒包裹ISA对单核/巨噬细胞选择性的清除作用。设计、时间及地点：分组设计、对比观察,于2003/2007分别在以色列希伯莱大学和解放军总医院实验室完成。材料：ISA由以色列希伯莱大学药学院合成;聚乳酸/乙醇酸共聚物（50∶50）,相对分子质量123400;聚乙烯醇,相对分子质量30000-70000。方法：采用双相乳化系统和溶剂蒸发技术制备纳米粒包裹的ISA,另以ISA溶液和等量不含ISA的纳米粒为对照。主要观察指标：①纳米粒形态、大小及纳米粒中ISA含量。②纳米粒中ISA体外释放率。③ISA对培养巨噬细胞、平滑肌细胞增殖的影响。④激光扫描共聚焦显微镜观察培养细胞对荧光标记纳米粒吞噬作用。结果：所制备的纳米粒直径500nm,表面呈负电荷（-40mV）,ISA包裹率高（17.6%-19.0%）,扫描电镜检查见其大小均匀。体外实验证实,ISA在纳米粒包裹后对巨噬细胞、平滑肌细胞增殖抑制作用明显增加,并且对巨噬细胞增殖的抑制作用尤为明显。激光扫描共聚焦显微镜观察发现荧光标记的纳米粒分别与巨噬细胞、平滑肌细胞孵育后,纳米粒可快速进入巨噬细胞内,且包裹ISA的纳米粒对巨噬细胞有明显损伤作用,而平滑肌细胞内无纳米粒。结论：ISA经纳米粒包裹后可选择性清除单核/巨噬细胞,而对非吞噬细胞影响较小。

摘要：目的:全麻中两种以上的药物合并应用比单一麻醉剂更为有效。本研究是为确定中国成年患者全麻期间合并应用七氟醚与瑞芬太尼时药物相互作用的方式,并以反应曲面模型法对其进行表述。方法:1.试验设计:研究采用平行实验设计,65例病人(ASAI级,各项指标正常,无长期服用阿片类药物史)入选本次试验,随机选定并维持一定的呼末七氟醚浓度[≤2MAC(0.3 %-3.4 %)] ,逐渐增加靶控输注的瑞芬太尼浓度(≤10 ng/mL) ,观察不同浓度组合时患者对喉镜置入刺激的反应以确定麻醉是否完全。2.反应曲面模型法进行药物动力学/药效动力学分析:两药合用的效果通过对喉镜置入时的反应进行评估,0和1分别代表有或没有体动反应。以下面的药效学模型表述体动反应消失的概率(P)其中Us ,Ur分别为标准化的七氟醚与瑞芬太尼水平;U50为达最大效应一半时的药物综合标准化水平;r为形状因子;I(Q)为药物相互作用的强度函数。模型通过作图、目标函数改变以及参数的生理/临床学的合理性等几方面进行评价。P=[U50/I((QU)s]+r+U(r)Urs+Ur)r结果与结论:研究表明瑞芬太尼与七氟醚合用时为协同式相互作用,上述反应曲面模型与实际观测值有较好的拟合。应用NONMEM得到喉镜置入刺激时的参数(RSE%)为U50=6.62(10.6) ,C50 ,sevo=1.71 %(12.9) ,C50 ,remi=12.4 ng/mL(19.0) ,Imax=2.31 ,Qmax=0.706。所得数值的加权残差均小于3。结果表明与传统方法相比,反应曲面模型法可以得到较好的拟合质量,为药物相互作用的研究提供了一种新颖思路和有效手段。