玉屏风散抗OVA致小鼠过敏性哮喘的作用研究

目的:观察玉屏风散(YPFS)抗OVA致小鼠过敏性哮喘的作用.方法:建立OVA诱导的小鼠过敏性哮喘模型,第0,14天,分别腹腔注射20 μg OVA,自21 d时开始雾化吸入0.5％ OVA溶液20 min,连续7d.空白对照组给予同体积的生理盐水.YPFS低、中、高剂量组每天分别灌胃给予玉屏风散生药3.25,6.5,13 g·kg-1,模型组和空白对照组给予同体积生理盐水,阳性药组从雾化期开始腹腔注射地塞米松(DEX)1 mg·kg-1.最后一次OVA雾化后24h取血,进行血中嗜酸性粒细胞(Eos)计数,血清中IgE测定;收集支气管灌洗液(BALF)进行细胞计数、分类;取右侧肺组织研磨匀浆,检测细胞因子IL-4,IFN-γ,左侧肺上叶做病理组织学观察.结果:模型组血中Eos及血清中IgE显著增高,BALF中出现大量Eos,肺组织病理显示支气管浆液性渗出,小管上皮细胞脱落,管腔狭窄或闭塞,且肺泡间隔变宽增厚,支气管周围淋巴细胞浸润.肺组织匀浆中IL-4增加,IFN-γ/IL-4显著降低,YPFS各剂量组能降低血中Eos及血清中IgE含量,减少BALF中Eos,减轻上述模型的病理改变.同时降低肺组织匀浆中IL-4含量,提高IFN-γ/IL-4.结论:玉屏风散对OVA导致的过敏性哮喘有明显的抑制作用,表现为降低哮喘小鼠的血中Eos,IgE分泌,肺组织炎症细胞的浸润.同时降低肺匀浆中IL-4的水平,提高IFN-γ/IL-4,抑制Th细胞向Th2极化.     

Sequential Methotrexate and 5-Fluorouracil as Second-Line Chemotherapy for Advanced Colorectal Cancer Patients Pretreated with 5-Fluorouracil and Leucovorin: a GISCAD Study

Abstract

The biochemical modulation of 5-fluorouracil (5-FU) by means of methotrexate (MTX) and 6-S leucovorin (LV) seems mainly directed at two different intracellular targets, supporting the hypothesis of possible non-cross resistance between these two methods of 5-FU potentia-tion. Thirty-one patients, all previously treated with 5-FU and LV for advanced colorectal cancer (ACC), were treated with MTX=200 mg/m² iv day 1 and 5-FU 600 mg/m² day 2 with 6-S LV 10 mg/m² po q 6 h X 6 starting 24 h after MTX, repeated every 2 weeks. Of 30 eva-luable patients, 2 Partial Remissions (PR) were achieved (Response Rate=6.6%; 95% Confidence Interval 0%-14%). Eight patients had disease stabilization (SD). The overall median survival was 5 months (range 1-11). No WHO grade III-IV toxicities were reported. Despite the good tolerability, this combination of MTX, 5-FU and LV rescue has minimal activity in ACC after the failure of 5FU+LV-based chemotherapy.     

Nanotube x-ray for cancer therapy: a compact microbeam radiation therapy system for brain tumor treatment

Microbeam radiation therapy (MRT) is a promising preclinical modality for cancer treatment, with remarkable preferential tumoricidal effects, that is, tumor eradication without damaging normal tissue functions. Significant lifespan extension has been demonstrated in brain tumor-bearing small animals treated with MRT. So far, MRT experiments can only be performed in a few synchrotron facilities around the world. Limited access to MRT facilities prevents this enormously promising radiotherapy technology from reaching the broader biomedical research community and hinders its potential clinical translation. We recently demonstrated, for the first time, the feasibility of generating microbeam radiation in a laboratory environment using a carbon nanotube x-ray source array and performed initial small animal studies with various brain tumor models. This new nanotechnology-enabled microbeam delivery method, although still in its infancy, has shown promise for achieving comparable therapeutic effects to synchrotron MRT and has offered a potential pathway for clinical translation.     

Immunotherapy opportunities in ovarian cancer

Ovarian cancer is responsible for the majority of gynecologic cancer deaths and despite the highest standard of multimodality therapy with surgery and cytotoxic chemotherapy, long-term survival remains low. With compelling evidence that epithelial ovarian cancer is an immunogenic tumor capable of stimulating an antitumor immune response, renewed efforts to develop immune therapies to augment the efficacy of traditional therapies are underway. Current immunotherapies focus on varied modes of antitumor vaccine development, particularly with the use of dendritic cell vaccines, effective methods for adoptive T-cell transfer and combinatorial approaches with immune modulatory therapy subverting natural tolerance mechanisms or boosting effector mechanisms. Additional combinatorial approaches include the use of cytokines and/or chemotherapy with immune therapy.     

病毒感染后表达下调的RNF167抑制小鼠腹腔巨噬细胞产生IFN-β

目的探讨RNF167对病毒感染的小鼠腹腔巨噬细胞产生IFN-β的调控作用。方法 RNA病毒VSV和DNA病毒HSV-1感染小鼠腹腔巨噬细胞后,Western blot检测RNF167的表达水平。利用RNA干扰减少小鼠原代腹腔巨噬细胞中RNF167的表达后,病毒感染小鼠腹腔巨噬细胞,实时荧光定量PCR法检测IFN-β的mRNA水平,ELIAS法检测细胞上清中IFN-β的浓度。Western blot法检测IFN-β的转录因子IRF3的磷酸化(p-IRF3)水平。结果VSV感染巨噬细胞4和8 h后,RNF167表达水平显著下降(P0.01),而HSV-1感染后RNF167的表达没有显著变化。si-RNF167降低小鼠腹腔巨噬细胞RNF167表达水平后,与对照细胞相比,感染RNA病毒后细胞中IFN-β的mRNA水平及上清中IFN-β水平显著下降(P0.01),p-IRF3水平也显著下降。而感染HSV-1病毒后上述指标均无差异。结论 RNF167能够特异性地调控RNA病毒感染的巨噬细胞中IFN-β的表达。     

湿疹方治疗湿疹45例

目的:观察湿疹方治疗湿疹的临床疗效及对外周血白介素-4(interleukin-4,IL-4)、白介素-10(interleukin-10,IL-10)、干扰素-γ(Interferon-γ,IFN-γ)水平的影响。方法:将90例患者随机分为对照组和治疗组,每组各45例。对照组采用盐酸西替利嗪联合复方甘草酸苷口服,治疗组在对照组的基础上使用湿疹方,共治疗4周。观察两组患者的临床疗效及治疗前后IL-4、IL-10、IFN-γ变化情况。结果:对照组有效率为75.56%,治疗组有效率为88.89%,两组有效率比较,差异具有统计学意义(P0.05)。两组患者治疗后IL-4、IL-10水平均较治疗前升高,且优于对照组,差异均有统计学意义(P0.05)。两组患者治疗后IFN-γ水平较治疗前降低,且优于对照组,差异均有统计学意义(P0.05)。结论:湿疹方治疗湿疹疗效显著,可能主要通过升高IL-4、IL-10水平,降低IFN-γ水平起到抗炎作用。     

Wound healing potential of naringin ointment formulation via regulating the expression of inflammatory,apoptotic and growth mediators in experimental rats

Context: Wound healing is a consequence of a complex process involving inflammatory, proliferative, and remodeling phases. Naringin, a flavanone glycoside, is associated with modulation of various oxido-inflammatory and growth factors.

Aim: The aim of this study is to evaluate the wound-healing activity of naringin ointment formulation (NOF) on experimental wound models.

Materials and methods: A soft paraffin-based cream containing 1, 2, and 4% (w/w) naringin was formulated and evaluated for physicochemical characters. Excision wounds and incisions wounds were used to study the topical effect of NOF for 20 d (once a day) on various biochemical, molecular, and histological parameters.

Results: NOF (2 and 4%, w/w) treatment showed a significant decrease (p?<?0.05) in wound area and epithelization period whereas the rate of wound contraction increased significantly (p?<?0.05). The altered levels of oxido-nitrosative stress (SOD, GSH, MDA, MPO, and NO) were significantly (p?<?0.05) restored by NOF. Treatment produced a significant increase (p?<?0.05) in tensile strength, hydroxyproline content, and protein content. TNF-α, IL-1β, IL-6, IL-8, NF-κB, smad-7, and Bax mRNA expression were significantly down-regulated (p?<?0.05) by NOF, whereas polymerase gamma (pol-γ), smad-3, VEGF and TGF-β, and collagen-1 mRNA expressions were significantly up-regulated (p?<?0.05) by NOF. Histological alterations in wound skin were also restored by NOF.

Conclusion: NOF exerts wound healing potential via down-regulated expression of inflammatory (NF-κB, TNF-α, and ILs), apoptotic (pol-γ and Bax), and up-regulated growth factor (VEGF and TGF-β) expression, thus modulating collagen-1 expression to induce angiogenesis leading to wound healing.     

In vitro inhibitory effects of thymol and carvacrol on dendritic cell activation and function

Context: Thyme has been used in traditional medicine for medicinal purposes since ancient times.

Objective: The objective of this study was to investigate the effects of thymol and carvacrol as two major constituents of thyme on dendritic cells (DCs) maturation and T cell activation.

Materials and methods: Splenic DCs were treated with non-cytotoxic concentrations of the components and then analyzed for MHC II, CD86, and CD40 expression by flow cytometry. The effects of compounds on mitogenic, as well as allogenic T cell responses in mixed lymphocyte culture (MLR) and the release of cytokines were investigated.

Results: At 0.1?µg/ml, reduced mean fluorescent intensity (MFI) of CD86 for thymol (80.3?±?0.2% of untreated control) and CD40 for carvacrol (79.5?±?0.14%) was observed (p?<?0.001). Decreased mitogenic T cell proliferation by thymol [proliferation index (PI) from 0.93?±?0.11 at 1?µg/ml to 0.42?±?0.16 at 100?µg/ml (p?<?0.01)] and carvacrol [PI from 1.08?±?0.3 at 1?µg/ml to 0.28?±?0.1 at 100?µg/ml (p?<?0.001)] was seen. Ten micrograms/ml thymol (PI, 0.85?±?0.04) and carvacrol (PI, 0.89?±?0.03) inhibited allogenic T cell response (p?<?0.05). Decreased IFN-γ level in MLR supernatant from 1441?±?27.7?pg/ml in untreated cells to 944?±?32.1 at 10?µg/ml of thymol and of carvacrol (886?±?31.7?pg/ml) (p?<?0.01) was found. IL-4 levels were decreased in the presence of both compounds (p?<?0.01).

Conclusion: These data showed the suppressive effects of thymol and carvacrol on DCs maturation and function, as well as T cell responses.     

Plasma IL-4, IL-8, IL-12, interferon-γ and CRP levels in pregnant women with preeclampsia,and their relation with severity of disease and fetal birth weight

Objective: The aim of the present study was to evaluate the hypothesis that preeclampsia is associated with increased systemic inflammatory responses of Th1-type as well as decreased Th2-type responses compared with normal pregnancy. We also sought to determine whether there was a correlation between these markers with severity of preeclampsia and fetal birth weight. Methods: The study population consisted of maternal age, gestational age, and body mass index matched 138 pregnant women; 56 normotensive healthy pregnant women (group 1), 42 women with mild preeclampsia (group 2), 40 women with severe preeclampsia (group 3). Results: Plasma interleukin (IL)-8 and C-reactive protein (CRP) levels were significantly higher in group 3 than group 1 (p?<?0.05). Plasma IL-4, IL-12, and interferon (IFN)-γ levels were similar in all groups. Although plasma IL-8 and CRP levels of mild preeclamptic group were higher than control group and lower than severe preeclamptic group, the differences were not statistically significant. There was a positive correlation between IL-12 and fetal birth weight in severe preeclamptic group (p?<?0.05). Conclusions: Elevated maternal serum pro-inflammatory cytokine IL-8 and CRP in severe preeclamptic women compared with normal pregnant women supports the hypothesis that preeclampsia is associated with increased inflammatory responses.