Shared impairment in associative learning in schizophrenia and bipolar disorder

Background

Schizophrenia (SCZ) and bipolar disorder (BD) share some cognitive commonalities. However, the role of associative learning, which is a cornerstone of human cognition mainly relying on hippocampus, has been under-investigated. We assessed behavioral performance during associative learning in a group of SCZ, BD and healthy controls (HC).

Methods

Nineteen patients with SCZ (36 ± 8.1 years; 13 males, 6 females; all Caucasians), 14 patients with BD (41 ± 9.6 years; 5 males, 9 females; all Caucasians) and 45 HC (27.7 ± 6.9 years; 18 males, 27 females; all Caucasians) were studied. Learning was assessed using an established object-location paired-associative learning paradigm. Subjects learned associations between nine equi-familiar common objects and locations in a nine-location grid. Performance data were analyzed in a repeated measures analysis of variance with time (repeated) and group as factors.

Results

Learning curves (performance = 1−e^−k?time) fitted to average performance data in the three groups revealed lower learning rates in SCZ and BD (k = 0.17 and k = 0.34) than HC (k = 0.78). Significant effects of group (F = 11.05, p < 0.001) and time (F = 122.06, p < 0.001) on learning performance were observed.

Conclusions

Our study showed that associative learning is impaired in both SCZ and BD, being potentially not affected by medication. Future studies should investigate the neural substrates of learning deficits in SCZ and BD, particularly focusing on hippocampus function and glutamatergic transmission.     

三氧化二砷诱导白血病细胞凋亡与核因子-κB活化的关系

为了研究三氧化二砷（As2O3）诱导白血病细胞凋亡与核因子-κB（NF-κB）活化以及血管内皮生长因子（VEGF）、基质金属蛋白酶-9（MMP9）表达的关系,应用流式细胞仪Annexin V FITC法检测白血病细胞系K562-n凋亡;采用免疫组织化学方法半定量分析K562-n细胞NF-κB、VEGF、MMP9表达的动态变化.结果显示：As2O3在诱导K562-n细胞凋亡的过程中可活化NF-κB,而VEGF、MMP9的表达也随之增强.地塞米松（DXM）1μmol/L能显著增加As2O3诱导K562-n细胞凋亡的作用和抑制K562-n细胞NF-κB活化,细胞凋亡增加率为43.04%,（P＜0.05）,NF-κB活化抑制率为31.15%（P＜0.05）,VEGF、MMP9变化与NF-κB一致.结论：As2O3诱导K562-n细胞凋亡的过程中可使NF-κB活化,VEGF、MMP9表达亦随之增强;DXM可通过抑制NF-κB活化增强其诱导K562-n细胞凋亡的作用,VEGF、MMP9的表达也随之下降.     

Increased extracellular matrix density decreases MCF10A breast cell acinus formation in 3D culture conditions

The extracellular matrix (ECM) contributes to the generation and dynamic of normal breast tissue, in particular to the generation of polarized acinar and ductal structures. In vitro 3D culture conditions, including variations in the composition of the ECM, have been shown to directly influence the formation and organization of acinus‐like and duct‐like structures. Furthermore, the density of the ECM appears to also play a role in the normal mammary tissue and tumour formation. Here we show that the density of the ECM directly influences the number, organization and function of breast acini. Briefly, non‐malignant human breast MCF10A cells were incubated in increasing densities of a Matrigel®–collagen I matrix. Elastic moduli near and distant to the acinus structures were measured by atomic force microscopy, and the number of acinus structures was determined. Immunochemistry was used to investigate the expression levels of E‐cadherin, laminin, matrix metalloproteinase‐14 and ß‐casein in MCF10A cells. The modulus of the ECM was significantly increased near the acinus structures and the number of acinus structures decreased with the increase in Matrigel–collagen I density. As evaluated by the expression of laminin, the organization of the acinus structures present was altered as the density of the ECM increased. Increases in both E‐cadherin and MMP14 expression by MCF10A cells as ECM density increased were also observed. In contrast, MCF10A cells expressed lower ß‐casein levels as the ECM density increased. Taken together, these observations highlight the key role of ECM density in modulating the number, organization and function of breast acini. Copyright © 2013 John Wiley & Sons, Ltd.     

辣椒碱对肝癌SMMC-7721细胞迁移和侵袭的影响及机制

目的:观察辣椒碱(capsaicin)对肝癌SMMC-7721细胞迁移和侵袭的影响及可能的分子机制。方法:设立不同浓度辣椒碱组以及空白组,采用细胞计数试剂盒-8法(CCK-8)检测辣椒碱(0,25,50,75,100,150,200,250μmol·L-1)处理肝癌SMMC-7721细胞24 h后的细胞活性;穿透小室(transwell)检测辣椒碱(0,50,75,100μmol·L-1)的肝癌SMMC-7721细胞迁移和侵袭能力;蛋白质免疫印迹法(Western blot)检测辣椒碱(0,50,75,100μmol·L-1)处理肝癌SMMC-7721细胞24 h后,对细胞中的E-钙黏蛋白(E-cadherin),波形蛋白(Vimentin),基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)和(matrix metalloproteinase-9,MMP-9)蛋白表达水平的影响。结果:与空白组比较,辣椒碱(25,50,75,100μmol·L-1)作用24 h后均对细胞存活率未产生明显影响,从150μmol·L-1开始,随着辣椒碱浓度逐渐升高,细胞存活率逐渐下降(P0.01),且呈剂量依赖效应;与空白组比较,辣椒碱(50,75,100μmol·L-1)干预能显著抑制肝癌SMMC-7721细胞迁移和侵袭,且呈浓度依赖效应(P0.01);与空白组比较,辣椒碱(50,75,100μmol·L-1)干预能明显上调肝癌SMMC-7721细胞中E-cadherin蛋白表达水平(P0.01),下调Vimentin,MMP-2,MMP-9蛋白的表达水平(P0.01)。结论:辣椒碱干预对肝癌SMMC-7721细胞迁移和侵袭具有抑制作用,可能与其上调肝癌SMMC-7721细胞中E-cadherin蛋白的表达,下调肝癌SMMC-7721细胞中Vimentin,MMP-2和MMP-9蛋白的表达有关。     

Chinese herbal medicine-derived compounds for cancer therapy: A focus on hepatocellular carcinoma

Ethnopharmacological relevance

Hepatocellular carcinoma (HCC) as the major histological subtype of primary liver cancer remains one of the most common malignancies worldwide. Due to the complicated molecular pathogenesis of HCC, the option for effective systemic treatment is quite limited. There exists a critical need to explore and evaluate possible alternative strategies for effective control of HCC. With a long history of clinical use, Chinese herbal medicine (CHM) is emerging as a noticeable choice for its multi-level, multi-target and coordinated intervention effects against HCC. With the aids of phytochemistry and molecular biological approaches, in the past decades many CHM-derived compounds have been carefully studied through both preclinical and clinical researches and have shown great potential in novel anti-HCC natural product development. The present review aimed at providing the most recent developments on anti-HCC compounds derived from CHM, especially their underlying pharmacological mechanisms.

Materials and methods

A systematic search of anti-HCC compounds from CHM was carried out focusing on literatures published both in English (PubMed, Scopus, Web of Science and Medline) and in Chinese academic databases (Wanfang and CNKI database).

Results

In this review, we tried to give a timely and comprehensive update about the anti-HCC effects and targets of several representative CHM-derived compounds, namely curcumin, resveratrol, silibinin, berberine, quercetin, tanshinone II-A and celastrol. Their mechanisms of anti-HCC behaviors, potential side effects or toxicity and future research directions were discussed.

Conclusion

Herbal compounds derived from CHM are of much significance in devising new drugs and providing unique ideas for the war against HCC. We propose that these breakthrough findings may have important implications for targeted-HCC therapy and modernization of CHM.     

盐酸米诺环素联合替硝唑治疗2型糖尿病合并牙周病的临床研究

目的 利用盐酸米诺环素对2型糖尿病牙周病进行辅助治疗,以探讨其临床疗效和作用机制。方法 选取2012年3月-2014年3月中国人民解放军空军总医院口腔科就诊的2型糖尿病合并牙周炎患者86例随机分组,其中,治疗组43例（91牙）,对照组43例（87牙）。对照组进行口腔龈上洁治术后使用浓替硝唑含漱液5 mL,保留2 min后吐出,并进行龈下刮治术。治疗组在对照组基础上,刮治完毕后将盐酸米诺环素挤入牙周袋内至溢出为止,1次/周,连续治疗4周。治疗结束后,比较两组的临床疗效,并检测两组治疗前后牙周指数、IL-Iβ和MMP-3的变化情况。结果 治疗组和对照组的总有效率分别为85.71%、66.67%,两组比较差异有统计学意义（P〈0.01）。治疗后两组患者菌斑指数、出血指数、牙周袋深度和附着丧失均较治疗前明显改善,同组治疗前后差异有统计学意义（P〈0.01）;治疗后,治疗组各指标均优于对照组,两组比较差异有统计学意义（P〈0.05,0.01）。治疗后两组患者龈沟液量、IL-Iβ、MMP-3水平均较治疗前明显减少,同组治疗前后差异有统计学意义（P〈0.01）;治疗后,治疗组龈沟液量、IL-Iβ与对照组相比差异有统计学意义（P〈0.01）。结论 盐酸米诺环素能够改善2型糖尿病合并牙周病患者的炎性因子水平,提高临床治疗效果,值得临床推广应用。     

肾癌中MMP9、MMP11与细胞增殖活性和血管生成的关系

目的观察基质金属蛋白酶9（MMP9）和基质金属蛋白酶11（MMP11）在肾细胞癌组织中的表达及其与细胞增殖活性和血管生成的关系。方法应用免疫组织化学染色方法检测32例肾细胞癌组织中MMP9、MMP11、第八因子相关抗原（FⅧ RAg）、α-平滑肌肌动蛋白（α-SMA）和增殖细胞核抗原（PCNA）的表达。结果MMP9和MMP11在瘤栓中呈强阳性表达,MMP9与MMP11均与FⅧ、α-SMA及PCNA表达密切相关。结论MMP9与MMP11在肾细胞癌增殖活性和血管生成方面均有重要作用。     

Increased mucosal matrix metalloproteinase-1, -2, -3 and -9 activity in patients with inflammatory bowel disease and the relation with Crohn''s disease phenotype

BACKGROUND AND OBJECTIVE: Matrix metalloproteinases are associated with matrix turnover in both physiological and pathological conditions. We postulate an association between aberrant matrix metalloproteinases proteolytic activity and the intestinal tissue destruction, seen in patients with Crohn's disease and/or ulcerative colitis. MATERIALS AND METHODS: Surgically resected inflamed and non-inflamed ileum and colon with/without extensive fibrosis from 122 Crohn's disease, 20 ulcerative colitis and 62 control patients were homogenized. Protein levels of matrix metalloproteinases and tissue inhibitor of metalloproteinases were measured by enzyme-linked immunosorbent assays (ELISA), while matrix metalloproteinases and myeloperoxidase activity were measured by specific activity assays. RESULTS: Expression of total levels of matrix metalloproteinases-1, -2, -3 and -9 relative to tissue inhibitor of metalloproteinases-1 and -2 was increased in inflamed inflammatory bowel disease compared to non-inflamed inflammatory bowel disease and control intestinal mucosa. Also, net matrix metalloproteinases-1, -2, -3 and -9 activity in inflamed inflammatory bowel disease was increased, with similar expression profiles in Crohn's disease and ulcerative colitis. Within inflamed inflammatory bowel disease, a close correlation of matrix metalloproteinases with myeloperoxidase was observed. The expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases was similar in inflamed Crohn's disease tissue with or without extensive fibrosis and not related to fistulizing disease. CONCLUSIONS: We have shown increased net matrix metalloproteinases activity in intestinal inflammatory bowel disease tissue, likely to contribute to the tissue damage and remodelling seen in inflammatory bowel disease.     

人参皂苷Rh2抑制肝癌HepG2细胞迁移的实验研究

目的:研究人参皂苷Rh2对肝癌Hep G2细胞迁移的影响及其机制。方法:取对数生长期Hep G2细胞,Rh2(10~160μmol/L)诱导,同时设空白对照组,用CCK-8检测Rh2对细胞增殖影响;Transwell检测Rh2对细胞的迁移的影响;荧光素报告基因筛选可能的信号通路;Western blot检测Hep G2细胞中P-ERK、ERK、P-P38、P-38、P-JUK、JUK、MMP3等蛋白的表达;定量PCR方法检测AP1、MMP3基因的表达;荧光显微镜分别观察AP1、MMP3蛋白在细胞内的表达及分布。结果:CCK-8检测结果显示Rh2对肝癌Hep G2细胞生长抑制呈剂量和时间依赖性;Transwell检测显示Rh2对肝癌Hep G2细胞迁移有明显的抑制作用;荧光素报告基因筛选出AP1转录因子;Western blot检测结果显示P-ERK、MMP3蛋白表达水平呈下降趋势,PJUK、P-P38蛋白表达水平明显升高,ERK、JUK、P38蛋白则无明显变化;定量PCR方法结果显示:AP1、MMP3的基因表达下降。荧光结果显示:AP1、MMP3均分布在胞质内,随药物浓度的增加其荧光表达量减弱。结论:人参皂苷Rh2可通过激活MAPK通路来抑制肝癌Hep G2细胞的迁移。     

Natural History of Thoracic Aortic Aneurysms: Size Matters,Plus Moving Beyond Size

Thoracic aortic aneurysms (TAAs) are a prevalent and deadly disease that, without diagnosis and treatment, eventuates in life-threatening aortic dissection or rupture. While TAAs normally grow in an indolent manner, once a certain size (a “hinge point”) is reached, the risk of dissection, rupture, and death increases dramatically. By virtue of their common clinical “silence,” many TAAs are not diagnosed until such complications occur. While size is a helpful criterion for intervention, there is a need for parameters and markers besides aortic aneurysm size for use in diagnosing and monitoring TAAs so as to prevent natural complications of this disease.