Eholecystokinin octapeptide antagonizes apoptosis in human retinal pigment epithelial cells

Although cholecystokinin octapeptide-8 is important for neurological function, its neuroprotective properties remain unclear. We speculated that cholecystokinin octapeptide-8 can protect human retinal pigment epithelial cells against oxidative injury. In this study, retinal pigment epithelial cells were treated with peroxynitrite to induce oxidative stress. Peroxynitrite triggered apoptosis in these cells, and increased the expression of Fas-associated death domain, Bax, caspase-8 and Bcl-2. These changes were suppressed by treatment with cholecystokinin octapeptide-8. These results suggest that cholecystokinin octapeptide-8 can protect human retinal pigment epithelial cells against apoptosis induced by peroxynitrite.     

血清YKL-40蛋白水平与颈动脉斑块内新生血管形成的关系

目的 探讨血清YKL-40蛋白水平与颈动脉斑块内新生血管形成的关系。方法 收集2015年1月～2016年12月本院超声科首次发现有颈动脉斑块者575例为研究组,以同期无动脉斑块者500例为对照组; 应用超微血管成像(SMI)技术判断斑块内新生血管分级,并检测研究对象的血清YKL-40蛋白、血脂、炎性因子TNF-α、hsCRP、IL-6等指标水平。结果 ①与对照组比较,研究组TC、TG、LDLC水平明显升高,HDLC明显降低(P均<0.05); ②研究组的IL-6、TNF-α、hsCRP、Lp-PLA2、YKL-40蛋白水平与对照组存在明显差异(P<0.05); ③按SMI分级将研究组患者分为4组,4组患者的YKL-40蛋白、IL-6、TNF-α、hsCRP、Lp-PLA2、血脂水平存在明显差异(P均<0.05); ④YKL-40蛋白与炎性因子及血脂指标水平存在相关性(P均<0.05)。结论 血清YKL-40蛋白水平与颈动脉斑块内新生血管形成的严重程度有关,检测YKL-40蛋白水平对判断斑块的稳定性有益。     

高压性小脑出血的外科治疗

目的探讨外科手术治疗高压性小脑出血的疗效。方法分别采取单纯后颅凹减压术和后颅凹减压加侧脑室外引流治疗高压性小脑出血。结果28例行单纯后颅凹减压术,9例行后颅凹减压加侧脑室外引流术,血肿清除90%以上30例,70%以上7例,无再出血病例。治愈22例,好转10例,死亡5例。结论小脑出血病情凶险,积极手术可取得良好的治疗效果。     

Effects of prodynorphin deletion on striatal dopamine in mice during normal aging and in response to MPTP

Dynorphins, endogenous neuropeptides found in striatonigral neurons, have been observed to exhibit dopamine-inhibitory actions and under some circumstances possess intrinsic neurotoxic activity. To test the hypothesis that dynorphin suppression mitigates effects of aging on the striatal dopaminergic system, HPLC quantitation of dopamine and related amines was performed on striatal homogenates of wild-type (WT) mice and mice lacking the prodynorphin (Pdyn) gene at varying ages. Pdyn knockout (KO) mice at 10 and 20 months show significant elevations in striatal dopamine compared to 3-month mice. Differences in tyrosine hydroxylase (TH) immunoreactivity could not account for these findings, but phosphorylation of TH at Ser40, but not Ser31, was enhanced in aged Pdyn KO mice. Systemic administration of MPTP produced significant dopamine depletion in an age-dependent manner, but Pdyn deletion conferred no protection against MPTP-induced dopamine loss, arguing against a mechanism by which Pdyn deletion enhances dopaminergic neuron survival. The above findings demonstrate an age-dependent inhibitory effect of dynorphins on striatal dopamine synthesis via modulation of TH activity.     

长程蝶骨电极脑电图对颞叶痫灶的定位价值探讨

目的 探讨长程蝶骨电极脑电图对颞叶痫灶的定位价值.方法 回顾性分析经手术治疗的119例颞叶癫痫患者,将其术前的常规脑电图 蝶骨电极(以下简称常规蝶骨电极)与视频脑电图 长程蝶骨电极脑电图(以下简称长程蝶骨电极)检测结果进行分析,其定位结果与术中描记的皮层脑电图(ECoG)及深部脑电图(DEEG)结果进行比较.结果 痫样放电在常规蝶骨电极和长程蝶骨电极的总检出率分别为68.9%和94.1%;其定侧率各为67.1%和99.1%(P＜0.005).术中脑电图证实了术前的长程蝶骨电极脑电图定位准确率高,DEEG与长程蝶骨电极定位吻合率达98.2%.本组随访1～5年,总有效率为97.4%,效果优良为88.6%.结论 长程蝶骨电极对颞叶痫样放电的检出和定侧率高,且准确率高.准确定位可提高手术疗效.     

A novel biosensor based on intestinal 3D organoids for detecting the function of BCRP

Breast cancer resistance protein (BCRP), a key drug efflux transporter, significantly affects the therapeutic efficacy of many drugs. Thus, screening specific BCRP inhibitors and distinguishing between substrates and non-substrates of BCRP are valuable in drug discovery and development. This study presents a novel BCRP biosensor based on intestinal 3D organoids for rapid and sensitive detection of BCRP function. First, the crypts were isolated from mouse small intestine, and cultured in advanced DMEM/F12 medium to develop intestinal 3D organoids. Second, immunohistochemical studies demonstrated that BCRP protein in the organoids presented a similar expression and physiologic position to the small intestinal epithelium. Finally, the cultured organoids were treated in BCRP fluorogenic probe substrate Hoechst 33342 with or without BCRP inhibitor Ko143 and YHO-13177. The fluorescence intensity of Hoechst 33342 released from inner of the organoids was detected by microplate reader and the concentrations were calculated. Ko143 and YHO-13177 significantly inhibited the BCRP-mediated Hoechst 33342 transport in the 3D organoids. Consequently, a rapid and efficient biosensor has been successfully established to study BCRP, especially screening BCRP inhibitors in a high-throughput way.     

Targeted-gene silencing of BRAF to interrupt BRAF/MEK/ERK pathway synergized photothermal therapeutics for melanoma using a novel FA-GNR-siBRAF nanosystem

Melanoma is significantly associated with mutant BRAF gene, a suitable target for siRNA-based anti-melanoma therapy. However, a tumor-specific delivery system is a major hurdle for clinical applications. Here, we developed a novel nano-carrier, FA-GNR-siBRAF for safe topical application, which consists of folic acid (FA) as the tumor-targeting moiety, golden nanorods (GNR) providing photothermal capability to kill tumor cells under laser irradiation, and siRNA specifically silencing BRAF (siBRAF). The in vitro and in vivo results revealed that FA-GNR-siBRAF displayed high transfection rates, and subsequently induced remarkable gene knockdown of BRAF, resulting in suppression of melanoma growth due to the interruption of the MEK/ERK pathway. Combinatorial photothermal effects and BRAF knockdown by FA-GNR-siBRAF effectively killed tumor cells through apoptosis, with enhanced efficiency than individual treatments. Therefore, the FA-GNR-siBRAF simultaneously induced BRAF gene silencing and photothermal effects which achieved synergistic efficacy in the treatment of melanoma, paving a new path for developing clinical treatment methods for melanoma.     

Membrane Loaded Copper Oleate PEGylated Liposome Combined with Disulfiram for Improving Synergistic Antitumor Effect <Emphasis Type="BoldItalic">In Vivo</Emphasis>

Purpose

This work aims to create a novel Cu²⁺ liposome with excellent loading stability and develop synergistic effect with disulfiram (DSF) for the treatment of tumor.

Methods

Copper oleate was incorporated into the liposome membrane via alcohol injection method in this work. In vitro release test was applied to evaluate the release profile of the liposomes. Pharmacokinetic studies were performed in rats and the antitumor efficacy was assessed in mice bearing hepatoma xenografts.

Results

The copper oleate liposome (Cu(OI)₂-L) was formulated and the loading efficiency were more than 85%. TEM images confirmed that the Cu(OI)₂-L had a spherical morphology with an average diameter of 100 nm. Cu(OI)₂-L displayed a biphasic release profile, with >70% retained drug over 8 h incubation in PBS at pH 7.4. Pharmacokinetic studies demonstrated that Cu(OI)₂-L had a prolonged circulation time and increased AUC when compared to the injection of copper oleate solution. The antitumor efficacy test demonstrated an enhanced tumor inhibition rate with the treatment of Cu(OI)₂-L and DSF nanoparticles, indicating an improved synergistic antitumor effect.

Conclusions

The Cu(OI)₂-L was suitable to be employed in combination with disulfiram for tumor treatment and can also open up opportunities for targeted delivery of copper.

     

Construction and immunogenicity of recombinant adenovirus expressing ORF2 of PCV2 and porcine IFN gamma

The capsid structural protein encoded by the gene ORF2 of Porcine Circovirus Type 2 is critical for eliciting the broad protective immunity. We constructed and characterized the recombinant adenovirus encoding the capsid and porcine IFN gamma, designated as rAd-ORF2-IFN-γ. The construct was further confirmed by the enzyme digestion, PCR, sequencing and transfection. The humoural immunity to the capsid protein, induced by the recombinant in the mice, was tested by ELISA. Notably, this recombinant induced a much better ORF2-specific antibody response than that of rAd-ORF2 alone or the adenovirus itself. Clearly, the porcine IFN gamma could strongly enhance the immunogenicity of ORF2. The results showed that the recombinant adenovirus might be an attractive candidate vaccine for preventing the disease associated with PCV2 infection.