Cellular internalization of doxorubicin loaded star-shaped micelles with hydrophilic zwitterionic sulfobetaine segments

Four arm star-shaped poly(ε-caprolactone)-b-poly((N,N-diethylaminoethyl methacrylate)-r-(N-(3-sulfopropyl)-N-methacryloxyethy-N,N-diethylammoniumbetaine)) (4sPCLDEAS) micelles were loaded with anticancer drug doxorubicin to track their endocytosis in Hela cancer cell line. The effects of mean diameters and surface charges of the drug loaded micelles on the cellular uptake were studied in details. The results demonstrated that the internalization of micelles was both time and energy dependent process. Endocytic pathways including clathrin-mediated endocytosis, caveolae-mediated endocytosis and macropinocytosis were all involved in the internalization; caveolae-mediated endocytosis was the main pathway for the internalization of 4sPCLDEAS micelles. The assays for cell apoptosis and growth inhibition of tumor spheroids identified that these doxorubicin loaded micelles could induce cell apoptosis and inhibit tumor spheroids growth efficiently, which was even equal to free DOX·HCl. This study provided a rational design strategy for fabricating diverse micellar drug delivery systems with high anticancer efficiency.     

Schisandra Chinensis Baill,A Chinese Medicinal Herb,Alleviates High-Fat-Diet-Inducing Non-Alcoholic Steatohepatitis in Rats

Background

he present study aims to explore whether Schisandra chinensis Baill, a Chinese, medicinal herb can alleviates high-fat-diet-inducing non-alcoholic steatohepatitis in rats.

Materials and Methods

In the study, 24, male Wister rats with body weight between 180-220g, were included. The rats were randomly divided into four groups: model group, normal control group, rosiglitazone group, and Schisandra chinensis Baill group. The treatment lasted for 56, days. The high-fat diet used in the present study includes 25% lard, 2%, cholesterol 0.5%, sodium cholate, and 25%, Tween-80. The hepatic levels of superoxide dismutase (SOD), and malondialdehyde (MDA); the serum levels of total cholesterol (TC), and low-density lipoprotein cholesterol (LDLC), were detected.

Results

We found that the hepatic levels of SOD were significantly lower, and the serum levels of TC, LDLC as well as, the hepatic levels of MDA in model group were significantly higher than those of normal control group; rosiglitazone group and Schisandra chinensis Baill group (P<0.05), indicates that non-alcoholic steatohepatitis rats were successfully induced by high-fat diet. Schisandra chinensis Baill group presented a significant lower serum levels of LDLC, than rosiglitazone group (P<0.05); and the hepatic levels of SOD in Schisandra chinensis Baill group were significantly lower than rosiglitazone group (P<0.05). However, no significant difference existed between Schisandra chinensis Baill group, and rosiglitazone group on the hepatic levels of MDA and the serum levels of TC (P>0.05).

Conclusion

It is then concluded that Schisandra chinensis Baill can significantly alleviate the non-alcoholic steatohepatitis of the rats induced by high-fat diet, and it may be used as a complementary therapy for rosiglitazone.     

Triggering receptor expressed on myeloid cells 2 knockdown exacerbates aging-related neuroinflammation and cognitive deficiency in senescence-accelerated mouse prone 8 mice

As a major characteristic of aging process, neuroinflammation is involved in the pathogenesis of several aging-related diseases including Alzheimer's disease (AD). Triggering receptor expressed on myeloid cells 2 (TREM2) is a newly identified risk gene for AD, which regulates inflammatory process in peripheral tissues via modulating the release of inflammatory cytokines. However, the role of TREM2 in aging-related neuroinflammation, cognitive deficiency, and AD-like neuropathology is unclear so far. Here, we detected the protein levels of TREM2 in brain of 3-, 7-, and 11-month-old senescence-accelerated mouse prone 8 (SAMP8) mice and observed that TREM2 levels were increased during aging process. We then knocked down TREM2 expression in brain of SAMP8 mice by nonviral RNA interference and found a significant increase in proinflammatory cytokines including tumor necrosis factor-α and interleukin (IL)-6, which was accompanied by a reduction in IL-10. Meanwhile, more obvious neuronal and synaptic losses and cognitive impairment were observed. These findings indicate that TREM2 may play a protective role against aging-related neuroinflammation and cognitive impairment.     

乙型脑炎Vero细胞灭活疫苗毒株的遗传稳定性

目的 研究流行性乙型脑炎Vero细胞灭活疫苗毒种（P3毒株）在生产过程中的遗传稳定性,为疫苗的安全性和免疫原性评价提供依据.方法 检测P3毒株鼠脑传代一代毒株、主种子、工作种子、疫苗及疫苗续传5代后病毒E蛋白基因核苷酸及氨基酸序列,并与GenBank中乙脑病毒P3株（AF036919）进行比对分析,同时比较主种子、工作种子、疫苗及疫苗续传5代后毒株的病毒滴度、抗原含量及效价.结果 以上5代次病毒的E蛋白基因核苷酸及蛋白质序列完全相同,同源性均为100％,与GenBank中乙脑病毒P3株（AF036919）比较显示：核苷酸序列中第E9、E10、E324、E330、E1223、E1338基因位点存在差异,同源性为99.73％,其中只有E1223突变引起相应氨基酸aE408突变（L→S）,同源性为99.80％,但该位点为非毒力相关位点,而其他位点均为沉默突变.4个代次疫苗毒株病毒滴度均≥8.0 lgLD50/ml,且各代次抗原含量及效价较为相似.结论 在生产乙型脑炎灭活疫苗（P3株）过程中建立的以Vero细胞为基质的乙脑毒种库具有良好的遗传稳定性.     

双镜联合微创治疗食管平滑肌瘤36例临床分析

目的 探讨电视胸腔镜(VATS)联合胃镜在食管平滑肌瘤治疗中的可行性及临床价值.方法 采用电视胸腔镜(VATS)联合胃镜行食管平滑肌瘤摘除术36例,位于食管下段24例,食管中段10例,食管上段2例.肿瘤大小1.0 cm×1.2 cm～ 4.0 cm×4.5 cm.结果 本组36例患者均在全胸腔镜下完成手术.1例术中发生食管黏膜破裂,全组患者术中手术时间(62.7±16.2)min,出血量(60.5±24.6)ml.术后胸腔引流管放置时间(2.1±1.3)d,开始进食时间为术后(2.4±1.8)d,术后住院时间(5.4±1.8)d.术后36例患者病理均为平滑肌瘤.除l例术中发生食管黏膜破裂外,余患者均无手术并发症和死亡发生.结论 胸腔镜联合胃镜治疗食管平滑肌瘤的方法安全、有效,可作为食管平滑肌瘤外科治疗的首选手术方式.     

Clinical profile of Parkinson's disease in the Gumei community of Minhang district,Shanghai

OBJECTIVE:

We examined the demographic and clinical profiles of Parkinson''s disease in Shanghai, China, to assist in disease management and provide comparative data on Parkinson''s disease prevalence, phenotype, and progression among different regions and ethnic groups.

METHODS:

A door-to-door survey and follow-up clinical examinations identified 180 community-dwelling Han-Chinese Parkinson''s disease patients (104 males, 76 females).

RESULTS:

The average age at onset was 65.16±9.60 years. The most common initial symptom was tremor (112 patients, 62.22%), followed by rigidity (38, 21.11%), bradykinesia (28, 15.56%) and tremor plus rigidity (2, 1.11%). Tremor as the initial symptom usually began in a single limb (83.04% of patients). The average duration from onset to mild Parkinson''s disease (Hoehn-Yahr phase 1–2) was 52.74±45.64 months. Progression from mild to moderate/severe Parkinson''s disease (phase≥3) was significantly slower (87.07±58.72 months; p<0.001), except for patients presenting initially with bradykinesia (53.83±24.49 months). Most patients (149/180, 82.78%) took levodopa with or without other drugs. The Hamilton Anxiety Scale revealed symptoms of clinical anxiety in 35 patients, and the Hamilton Depression Scale revealed depressive symptoms in 88 patients. The depressed or anxious subgroup (123 patients) demonstrated a significantly younger age at onset (55.54±7.68 years) compared with the overall mean (p<0.05).

CONCLUSION:

Unilateral limb tremor was the most common initial symptom, and motor function deteriorated slowly over ≈4−9 years. Earlier-onset patients experience greater psychiatric dysfunction.