肿瘤联合免疫治疗研究进展

免疫检查点是免疫系统中抑制性的信号通路,通过与共刺激分子保持平衡,维持对自身组织的耐受,避免自身免疫反应。肿瘤的发生伴随着共抑制分子与相关配体的上调,引起T细胞功能衰退或耗竭,从而发生肿瘤细胞的免疫逃逸。针对抑制性受体与配体开发单抗药物,调节T细胞活性提高抗肿瘤免疫反应,已经取得较好的临床效果。对免疫调节信号通路采取联合治疗也体现出一定的协同作用。本文对肿瘤联合免疫治疗方案与协同作用评价进行综述,并对联合免疫治疗的可行性及免疫方案的选择进行展望。     

Flavonoids from Sophora moorcroftiana and their Synergistic Antibacterial Effects on MRSA

Synergy is now a widely recognized approach that has direct applicability for new pharmaceuticals. The ethanolic extract of the aerial parts of the herb Sophora moorcroftiana showed significant antibacterial activity against drug‐resistant Staphylococcus aureus, and its minimum inhibitory concentration (MIC) was 8 µg/mL. In a phytochemical study of the extract, five flavonoids were obtained. However, the isolates exhibited antibacterial activity in the range of 32–128 µg/mL, which was weaker than the extract. In combination with antibiotics, the antibacterially inactive compound genistein (1) and diosmetin (4) showed significant synergistic activity against drug‐resistant S. aureus. In combination with norfloxacin, genistein (1) reduced the MIC to 16 µg/mL and showed synergy against strain SA1199B with a fractional inhibitory concentration index (FICI) of 0.38. With the antibiotics norfloxacin, streptomycin and ciprofloxacin, diosmetin (4) showed synergy against SA1199B, RN4220 and EMRSA‐15, with FICI values of 0.38, 0.38 and 0.09, respectively. In an efflux experiment to elucidate a plausible mechanism for the observed synergy, genistein showed marginal inhibition of the NorA efflux protein. Copyright © 2013 John Wiley & Sons, Ltd.     

Therapeutic Potential of Turmeric in Alzheimer's Disease: Curcumin or Curcuminoids?

Alzheimer's disease (AD) is the most common form of dementia. There is limited choice in modern therapeutics, and drugs available have limited success with multiple side effects in addition to high cost. Hence, newer and alternate treatment options are being explored for effective and safer therapeutic targets to address AD. Turmeric possesses multiple medicinal uses including treatment for AD. Curcuminoids, a mixture of curcumin, demethoxycurcumin, and bisdemethoxycurcumin, are vital constituents of turmeric. It is generally believed that curcumin is the most important constituent of the curcuminoid mixture that contributes to the pharmacological profile of parent curcuminoid mixture or turmeric. A careful literature study reveals that the other two constituents of the curcuminoid mixture also contribute significantly to the effectiveness of curcuminoids in AD. Therefore, it is emphasized in this review that each component of the curcuminoid mixture plays a distinct role in making curcuminoid mixture useful in AD, and hence, the curcuminoid mixture represents turmeric in its medicinal value better than curcumin alone. The progress in understanding the disease etiology demands a multiple‐site‐targeted therapy, and the curcuminoid mixture of all components, each with different merits, makes this mixture more promising in combating the challenging disease. Copyright © 2013 John Wiley & Sons, Ltd.     

三种AmpC酶表型检测方法比较

目的对革兰阴性菌产AmpC酶的检测方法进行评价,并寻找一种适合临床常规应用的AmpC酶检测方法。方法对39株耐头孢西丁的革兰阴性菌同时进行改良Hodge试验、三维试验、氯唑西林（CLO）双纸片协同试验和ampC基因聚合酶链反应（PCR）检测,比较4种方法的结果。结果39株革兰阴性杆菌中,改良Hodge试验、三维试验和CLO双纸片协同试验检出产AmpC酶的阳性率分别为38．5％、43．6％和28．2％,3种方法AmpC酶检出率的差异无统计学意义（P〉0．05）。与PCR结果比较,改良Hodge试验特异性为87％,敏感性为75％;三维试验的特异性为78％,敏感性为75％;CLO双纸片协同试验特异性为87％,敏感性为50％。PCR显示ampC基因阳性率为41％（16／39）,对16株阳性菌进行ampC基因测序,测序结果与基因数据库内相应的ampC核酸序列比对发现,同源性均在98％～100％之间。结论改良Hodge试验可作为一种操作快速、简便的筛选试验检测革兰阴性菌产AmpC酶的情况,而CLO双纸片协同试验可作为一种操作简便的排除产AmpC酶试验应用于实验室,但在准确性上低于改良Hodge试验。     

两种非核苷类逆转录酶抑制剂与已上市药物联合应用的体外抗HIV活性研究

目的：评价两种非核苷类逆转录酶抑制剂（JB25、JB26）与3种已上市药物齐多夫定（AZT）、依非韦仑（EFV）、沙奎那韦（SQV）联合应用的体外抗HIV活性。方法：将10个浓度的JB25、JB26分别与AZT、EFV、SQV的7个浓度组成各种浓度的组合,加入384孔细胞培养板,与HIV-1ⅢB急性感染的MT-2细胞共培养3d,最后利用TZMbl细胞报告基因检测HIV-1的表达,共重复3次。利用MacSynergyⅡ软件对数据进行分析,得到药物相互作用的情况。结果：JB25与AZT、EFV、SQV的平均协同/拮抗容量分别是244.45/-5.05,119.58/-65.93,145.83/-0.32（nmol/L）2%;JB26与AZT、EFV、SQV的平均协同/拮抗容量分别是398.90/0,103.62/-0.49,138.473/-0.27（nmol/L）2%。结论：两种非核苷类逆转录酶抑制剂与3种已上市的药物在体外联合应用,具有协同抗HIV作用,MacSynergyⅡ软件可以全面评价两种药物的联合作用情况。     

扶正消瘤液对肿瘤化疗增敏作用的临床研究

观察中药复方在肿瘤化疗增敏方面的作用。将 6 9例晚期肿瘤患者随机分为治疗组和对照组 ,治疗组用中药复方扶正消瘤液配合化疗进行临床治疗 ,并与单纯化疗组进行对照。两组化疗方法相同。结果 ,治疗组有效率为 31.5 8% ,对照组有效率为 2 2 .5 8% ,统计学处理差异明显 (P<0 .0 5 )。治疗组治疗前后 TL c TR、NKc A、s IL-2 R及对照组治疗后相比均有显著性差异。结论 ,中药复方扶正消瘤液对晚期肿瘤化疗有一定的增敏作用。     

Cell death mechanisms induced by synergistic effects of halofuginone and artemisinin in colorectal cancer cells

Our previous study found that the combination of halofuginone (HF) and artemisinin (ATS) synergistically arrest colorectal cancer (CRC) cells at the G1/G0 phase of the cell cycle; however, it remains unclear whether HF-ATS induces cell death. Here we report that HF-ATS synergistically induced caspase-dependent apoptosis in CRC cells. Specifically, both in vitro and in vivo experiments showed that HF or HF-ATS induces apoptosis via activation of caspase-9 and caspase-8 while only caspase-9 is involved in ATS-induced apoptosis. Furthermore, we found HF or HF-ATS induces autophagy; ATS can''t induce autophagy until caspase-9 is blocked. Further analyzing the crosstalk between autophagic and caspase activation in CRC cells, we found autophagy is essential for activation of caspase-8, and ATS switches to activate capase-8 via induction of autophagy when caspase-9 is inhibited. When apoptosis is totally blocked, HF-ATS switches to induce autophagic cell death. This scenario was then confirmed in studies of chemoresistance CRC cells with defective apoptosis. Our results indicate that HF-ATS induces cell death via interaction between apoptosis and autophagy in CRC cells. These results highlight the value of continued investigation into the potential use of this combination in cancer therapy.     

Generalization of motor module recruitment across standing reactive balance and walking is associated with beam walking performance in young adults

BackgroundRecent studies provide compelling evidence that recruiting a common pool of motor modules across behaviors (i.e., motor module generalization) may facilitate motor performance. In particular, motor module generalization across standing reactive balance and walking is associated with both walking speed and endurance in neurologically impaired populations (e.g., stroke survivors and individual’s with Parkinson’s disease). To test whether this phenomenon is a general neuromuscular strategy associated with well-coordinated walking and not limited to motor impairment, this relationship must be confirmed in neurologically intact adults.Research QuestionIs motor module generalization across standing reactive balance and walking related to walking performance in neurologically intact young adults?MethodsTwo populations of young adults were recruited to capture a wide range of walking performance: professionally-trained ballet dancers (i.e., experts, n = 12) and novices (n = 8). Motor modules (a.k.a. muscle synergies) were extracted from muscles spanning the trunk, hip, knee and ankle during walking and multidirectional perturbations to standing. Motor module generalization was calculated as the number of modules common to these behaviors. Walking performance was assessed using self-selected walking speed and beam-walking proficiency (i.e., distance walked on a narrow beam). Motor module generalization between experts and novices was compared using rank-sum tests and the association between generalization and walking performance was assessed using correlation analyses.ResultsExperts generalized more motor modules across standing reactive balance and walking than novices (p = 0.009). Across all subjects, motor module generalization was moderately associated with increased beam walking proficiency (r = 0.456, p = 0.022) but not walking speed (r = 0.092, p = 0.349).SignificanceSimilar relationships between walking performance and motor module generalization exist in neurologically intact and impaired populations, suggesting that motor module generalization across standing reactive balance and walking may be a general neuromuscular mechanism contributing to the successful control of walking.     

The ‘entourage effect’ or ‘hodge-podge hashish’: the questionable rebranding,marketing, and expectations of cannabis polypharmacy

ABSTRACT

Introduction

The concept of a cannabis ‘entourage effect’ was first coined as a hypothetical afterthought in 1998. Since then, multiple scientific reviews, lay articles, and marketing campaigns have promoted the effect as a wholly beneficial manifestation of polypharmacy expected to modulate the therapeutic effects of cannabis and its derivatives. There is reason to wonder at the authenticity of such claims.