Is the autophagy a friend or foe in the silver nanoparticles associated radiotherapy for glioma？

Malignant glioma is the most common intracranial tumor with a dismal prognosis. The radiosensitizing effect of silver nanoparticles (AgNPs) on glioma both in vitro and in vivo had been demonstrated in the previous studies of our group. However, the underlying mechanism is still unclear. Consistent with previous studies, a size and dose dependent antitumor effect and significant radiosensitivity enhancing effect of AgNPs were observed in our experiment system. We also found that cell protective autophagy could be induced by AgNPs and/or radiation, which was verified by the use of 3-MA. The mechanism through which had autophagy and the enhancement of radiosensitivity taken place was further investigated with inhibitors of ERK and JNK pathways. We demonstrated that ERK and JNK played pivotal roles in the radiosensitivity enhancement. Inhibiting ERK and JNK with U0126 and SP600125 respectively, we found that the autophagy level of the cells treated with AgNPs and radiation were attenuated. Moreover, SP600125 down-regulated the apoptosis rate of the co-treated cells significantly. Taken together, the present study would have important impact on biomedical applications of AgNPs and clinical treatment for glioma.     

Coordinate Bonding Strategy for Molecularly Imprinted Hydrogels: Toward pH-Responsive Doxorubicin Delivery

Molecularly imprinted hydrogel (MIH) as drug delivery system has been studied. It still remains a challenge to construct the stimuli-responsive MIH. Here, we report a coordinate bond strategy for imprinting doxorubicin (Dox) in hydrogel capable of pH-responsive and sustained drug delivery. The imprinting condition such as template–monomer interactions induced by metal ion was carefully investigated by spectroscopic methods. The obtained Dox–MIH was evaluated by absorption and in vitro release experiments. It has been demonstrated that the cupric ion mediated interaction between Dox and 4-vinyl pyridine via coordination and the optimal coordinate ratio of Dox/Cu²⁺ was 2:1. The rebinding amount of MIH to Dox was 2.7-fold that of nonimprinted hydrogel and the Dox-loaded MIH showed a pH-responsive release property. Not more than 10% of loaded drug was released from Dox–MIH at pH 7.2 during a time course of 7 days. However, near to 60% of loaded drug was sustainedly released at pH 5.0 during the same period. These results indicated that Dox–MIH with pH-responsive behavior possessed great promising as sustained-release delivery system of anticancer drug.     

Preventive effect of non-mitogenic acidic fibroblast growth factor on diabetes-induced testicular cell death

Fibroblast growth factor (FGF)-1 was found to protect the heart from oxidative damage, but clinically its long-term use was restricted for its undesirable proliferating activity on cells. Thus a cluster of amino acids responsible for the proliferation were deleted in the native FGF-1 to create a non-mitogenic FGF-1 (nmFGF-1). Whether the nmFGF-1 protects male germ cells from diabetes-induced apoptotic death was examined in diabetic mice induced with multiple low-doses of streptozotocin, followed by nmFGF-1 treatment for 6 months. Diabetic mice showed a decrease in testicular weight and an increase in apoptotic cell death. Treatment with nmFGF-1 alleviated the diabetic effects on testicular weight and apoptotic cell death. Mechanistically, nmFGF-1 may alleviate diabetes-induced germ cell death by decreasing the BAX/Bcl-2 ratio and endoplasmic reticulum stress as well as associated cell death, which is associated with Nrf-2 activation.     

逍遥散治疗糖尿病的网络药理学分析

新型冠状病毒肺炎（COVID-19）已成为全球性的重大疫情,中医药在重大疫情防控过程中发挥了重要作用。基于对COVID-19的认识以及中医药防控路径,以疏风解毒胶囊为例,概述了中医药针对早期干预、阻断病情进展、改善症状、抗炎免疫、抑制“细胞因子风暴”以及辨证分型、发挥配伍优势等方面的思路和研究实践,并提出中药新药研发科学模式建立的设想。     

The role of pleiotrophin in bone repair

Bone has an enormous capacity for growth, regeneration, and remodelling, largely due to induction of osteoblasts that are recruited to the site of bone formation. Although the pathways involved have not been fully elucidated, it is well accepted that the immediate environment of the cells is likely to play a role via cell–matrix interactions, mediated by several growth factors. Formation of new blood vessels is also significant and interdependent to bone formation, suggesting that enhancement of angiogenesis could be beneficial during the process of bone repair. Pleiotrophin (PTN), also called osteoblast-specific factor 1, is a heparin-binding angiogenic growth factor, with a well-defined and significant role in both physiological and pathological angiogenesis. In this review we summarise the existing evidence on the role of PTN in bone repair.     

一种人工合成Tuftsin类似肽大鼠组织分布和排泄研究

目的研究Tuftsin类似肽（T肽）单次皮下注射后在大鼠体内的组织分布特点和排泄情况。方法 Wistar大鼠,单次皮下注射剂量21.6 mg.kg-1T肽。采用竞争ELISA方法检测各时间点的组织器官、尿、粪和胆汁中的药物含量。结果组织分布试验结果表明,药物主要分布在大鼠的血清、肾、脾和小肠组织中,除小肠达峰时间为给药后2 h之外,其它药物含量均于给药后15 min达最高;排泄实验结果表明,0～144 h内尿和粪中排泄的原型药物分别占给药总量的2.21%和0.03%;0～96 h内大鼠胆汁中排泄的原型药物为给药总量的0.02%。结论 T肽给药后在Wistar大鼠体内广泛分布,在血清、肾和脾组织中含量较高,在粪和胆汁中检测出T肽的含量很少。     

Neuroprotection of Glycyrrhizin against Ischemic Vascular Dementia in vivo and Glutamate-induced Damage in vitro

Objective To evaluate the neuroprotective effects of glycyrrhizin (GL) on vascular dementia (VaD) in vivo and Glutamate-induced damage in vitro. Methods Male Wistar rats were subjected to permanent occlusion of the bilateral common carotid arteries. On d 15 postsurgery, rat cognition was assessed using the Morris water maze. The activity of superoxide dismutase and the content of malondialdehyde of brains were also measured. Brain damage was evaluated histologically using HE staining. In vitro cell viability was examined in PC12 cells exposed to Glutamate, and mRNA levels of Bcl-2 and Bax were assessed. Results GL (20 mg/kg for 12 d) improved the performance of learning and memory of VaD rats, decreased the level of lipid peroxidation, and attenuated the pathological alterations in the hippocampal CA1 and CA3 areas. Moreover, GL (0.6 mmol/L) could protect PC12 cell lines from injury induced by Glutamate (10 mmol/L) and inhibit apoptosis of neuronal cells. Conclusion The present findings suggest that GL may have therapeutic potential in treating VaD.     

Antioxidant treatment of hindlimb-unloaded mouse counteracts fiber type transition but not atrophy of disused muscles

Oxidative stress was proposed as a trigger of muscle impairment in various muscle diseases. The hindlimb-unloaded (HU) rodent is a model of disuse inducing atrophy and slow-to-fast transition of postural muscles. Here, mice unloaded for 14 days were chronically treated with the selective antioxidant trolox. After HU, atrophy was more pronounced in the slow-twitch soleus muscle (Sol) than in the fast-twitch gastrocnemius and tibialis anterior muscles, and was absent in extensor digitorum longus muscle. In accord with the phenotype transition, HU Sol showed a reduced expression of myosin heavy chain type 2A (MHC-2A) and increase in MHC-2X and MHC-2B isoforms. In parallel, HU Sol displayed an increased sarcolemma chloride conductance related to an increased expression of ClC-1 channels, changes in excitability parameters, a positive shift of the mechanical threshold, and a decrease of the resting cytosolic calcium concentration. Moreover, the level of lipoperoxidation increased proportionally to the degree of atrophy of each muscle type. As expected, trolox treatment fully prevented oxidative stress in HU mice. Atrophy was not prevented but the drug significantly attenuated Sol phenotypic transition and excitability changes. Trolox treatment had no effect on control mice. These results suggest possible benefits of antioxidants in protecting muscle against disuse.     

邻苯二甲醛-9-氯甲酸芴甲酯柱前衍生HPLC法测定血必净注射液中氨基酸

目的通过建立HPLC分析法测定血必净注射液中氨基酸,为提高中药注射液质量标准提供依据.方法通过OPA-FMOC柱前衍生化法,建立同时检测血必净注射液中18种常见氨基酸的液相色谱法.色谱柱为Agilent SB-C18柱(250mm×4.6 mm,5 μm);流动相A为0.02 mol/L醋酸钠溶液(含200μL/L三乙...