Sensory evoked potentials in patients with Rett syndrome through the lens of animal studies: Systematic review

ObjectiveSystematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).MethodsPubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards.ResultsERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients.ConclusionsWhile there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms.SignificanceThe review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology.     

Chemical composition and antiproliferative activity of essential oil from the leaves of a medicinal herb, Schefflera heptaphylla

Schefflera heptaphylla (L.) Frodin is a medicinal herb widely used as a main ingredient of the popular health tea formulation against infections in Southern China. Twenty-seven volatile compounds were identified by GC-MS analysis from the essential oil obtained from the leaves of S. heptaphylla, and 17 of them belonged to monoterpenes or sesquiterpenes. The main volatile constituent in S. heptaphylla was found to be a monoterpene, beta-pinene, comprising about 22% of the total volatile components. The essential oil showed significant antiproliferative activity against three cancer cell lines, MCF-7, A375 and HepG2 cells, with IC50 values of 7.3 microg/mL, 7.5 microg/mL and 6.9 microg/mL, respectively. The result of the cytotoxicity assay indicates that (-)-beta-pinene and (+)-beta-pinene (commercially available from Sigma) also possessed antiproliferative activity against the cancer cells MCF-7, A375 and HepG2 with IC50 values ranging from 147.1 to 264.7 microm.     

加温合并药物治疗Lewis肺癌的实验研究

本实验以荷 Lewis 肺癌的 NIH 小鼠为模型,以肿瘤平均直径倍增时间(MDDT)为终点,进行加温合并抗癌药物的研究。结果表明:①43℃加温25分钟,对 Lewis 肺癌有明显的治疗效果(P<0.05);②喜树碱16mg/kg合并加温25分钟,对 Lewis 肺癌的抑制作用随加热温度升高而加强,在43℃时出现相加作用(P<0.001);③斑蝥素0.45mg/kg,高三尖杉酯碱1.2mg/kg 或消瘤芥0.75mg/kg 合并加温25分钟,对Lewis 肺癌的抑制作用随加热温度升高而增强,其中斑蝥素和消瘤芥在43℃时出现协同作用(P<0.001);①去甲斑蝥酸钠3mg/kg 对 Lewis 肺癌无治疗作用,但合并43℃加温25分钟时有协同作用;⑤鸦胆子油口服乳液8ml/kg,间隔27小时合并43℃加温25分钟,对 Lewis 肺癌的治疗有相加作用,并明显延长了荷瘤动物的生存时间。     

舍蝇抗菌肽的提取及其对肿瘤细胞生长的抑制作用

目的：研究含蝇抗菌肽的提取对肿瘤细胞生长的抑制作用；方法：对舍蝇幼虫采用针刺损伤及金黄色葡萄球菌感染诱导方法，并通过研磨、加热、阳离子交换柱层析及Sephadex G—50葡聚糖凝胶柱层析等步骤提取抗菌肽；结果：经SDS—PAGE电泳分离到2条带，分子量分别为4kD，9．6kD；结论：提取的舍蝇抗菌肽能有效地抑制人胃癌细胞MGC80—3和BGC—823，人乳腺癌细胞MCF—7及人肺癌细胞SPC—A—1的体外增殖，并且呈浓度依赖关系。     

Determination of metabolites of a novel platinum anticancer drug JM216 in human plasma ultrafiltrates

The present study describes the application of on-line liquid chromatography-electrospray ionisation in conjunction with a high resolution magnetic sector mass spectrometer to identify metabolites of a platinum(IV) anticancer drug JM216 bis(acetato)amminedichloro(cyclohexylamine)platinum(IV)] in human plasma. Four metabolites were identified following incubation of JM216 in human plasma: JM118 [amminedichlorocyclohexylamineplatinum(II)], a platinum(II) complex; JM383 [bis(acetato)amminedihydroxo(cyclohexylamine)platinum(IV)]; JM518 [bis(acetato)amminechloro(cyclohexylamine)hydroxoplatinum(IV)] and its isomer JM559. The platinum complexes mass spectra were dominated by the natriated [M + Na]⁺ ion. Elemental compositions of these natriated ions were confirmed by accurate mass measurement on a magnetic sector mass spectrometer in the course of LC/MS analysis. This study demonstrates the capability of direct LC-ESI/MS with accurate mass measurement for analysis of platinum complexes in biological samples. Our results suggest that LC-ESI/MS is a powerful technique for structure elucidation of novel metabolites, and could make valuable contributions to drug metabolism research.     

Dihematoporphyrin ether-induced photosensitivity in laryngeal papilloma patients

Twenty-six patients with recurrent laryngeal papillomatosis received 2.5 mg/kg of Dihematoporphyrin Ether (DHE) intravenously prior to photodynamic therapy. All patients experienced some degree of photosensitivity, the only known side effect of DHE. Reported reactions included mild erythema and inflammation (88%), swelling (58%), blistering (23%), ocular discomfort (61.5%), pruritus (38%), and skin hyperpigmentation (46%). Length of sensitivity ranged from 4-17 weeks, with an average duration of 9 weeks. No long-term debilitating sequelae were noted. Degree of skin reaction mainly depended on how compliant the patient was in following precaution instructions. Although restrictive precautions were often difficult to strictly adhere to, most patients felt the potential benefits of the therapy far outweighed any inconvenience.     

硫杂蒽酮类光引发剂的合成

合成了12种烷基、烷氧基和硝基取代的硫杂蒽酮类化合物。其中,三种烷氧基取代的硫杂蒽酮是用相转移催化法制得的。几种新的化合物,经红外光谱、质谱和元素分析等方法鉴定,确证了其结构。测定了化合物的紫外吸收光谱。结果表明,硫杂蒽酮类化合物的2-位上是斥电子基时,其最大吸收波长要向红移动;若2-位上是吸电子基时则向紫移动。     

Cyclodextrins in Polymer Synthesis: Free Radical Polymerization of β‐Cyclodextrin Complexes of Photosensitive Mesoionic 6‐Oxo‐1,6‐dihydropyrimidin‐3‐ium‐4‐olates in Aqueous Medium

Solid mesoionic 2‐[2‐(isopropenylcarbonyloxy)ethylthio]‐1‐methyl‐6‐oxo‐3‐phenyl‐5‐propyl‐1,6‐dihydropyrimidin‐3‐ium‐4‐olate was complexed in water using β‐cyclodextrin (β‐CD) and randomly methylated β‐CD, which resulted in polymerizable complexes with 2:1 stoichiometry. The β‐CD complex was characterized using ¹H NMR, ROESY NMR and UV spectroscopy. Polymerization of the complex prepared from methylated β‐CD led to a photosensitive polymer, which precipitated during polymerization and was nearly free of CD. Polymerization was carried out with a water‐soluble redox initiator. In addition, a copolymer with methyl methacrylate was prepared from the complexes, which showed a different mass‐dependent distribution in the incorporation in comparison to a copolymer prepared without CD in organic solvents.

     

Cervical tissue uptake of all-trans-retinoic acid delivered via a collagen sponge-cervical cap delivery device in patients with cervical dysplasia

The present study was undertaken to evaluate the systemic absorption and cervical tissue uptake of all-transretinoic acid (TRA), delivered via a collagen spongecervical cap delivery device in patients with intraepithelial cervical dysplasia. Ten patients with histologically proven mild or moderate cervical dysplasia were included in this pharmacologic study. The two TRA concentrations (0.05% and 0.372%) selected for study represent the starting and maximally tolerated doses used in phase I clinical trial. All-trans-retinoic-11-³H acid (³H-TRA, 500 Ci) was used to facilitate cervical tissue uptake studies. Cervical biopsies and post-treatment blood samples were obtained from each patient after TRA exposure. The uptake of TRA into cervical tissues four hours after drug administration was significantly increased at the maximally tolerated TRA dose. There was a rapid decrease in cervical tissue concentration of TRA at the 0.372% dose between 4 and 24 h after drug exposure, suggesting a relatively short elimination half-life of TRA in cervical tissues. HPLC analysis of post-treatment blood samples indicate that there was no systemic absorption of TRA after local cervical administration.     

Anticancer Mechanism of Curcumin on Human Glioblastoma

Glioblastoma (GBM) is the most malignant brain tumor and accounts for most adult brain tumors. Current available treatment options for GBM are multimodal, which include surgical resection, radiation, and chemotherapy. Despite the significant advances in diagnostic and therapeutic approaches, GBM remains largely resistant to treatment, with a poor median survival rate between 12 and 18 months. With increasing drug resistance, the introduction of phytochemicals into current GBM treatment has become a potential strategy to combat GBM. Phytochemicals possess multifarious bioactivities with multitarget sites and comparatively marginal toxicity. Among them, curcumin is the most studied compound described as a potential anticancer agent due to its multi-targeted signaling/molecular pathways properties. Curcumin possesses the ability to modulate the core pathways involved in GBM cell proliferation, apoptosis, cell cycle arrest, autophagy, paraptosis, oxidative stress, and tumor cell motility. This review discusses curcumin’s anticancer mechanism through modulation of Rb, p53, MAPK, P13K/Akt, JAK/STAT, Shh, and NF-κB pathways, which are commonly involved and dysregulated in preclinical and clinical GBM models. In addition, limitation issues such as bioavailability, pharmacokinetics perspectives strategies, and clinical trials were discussed.