细胞因子IL-1β/ IFN-γ对骨骼肌成肌细胞基因表达的影响

目的研究细胞因子白细胞介素-1β(IL-1β)/干扰素-γ( IFN-γ)对鼠骨骼肌成肌细胞基因表达的影响.方法鼠骨骼肌成肌细胞在IL-1β/ IFN-γ混合液中孵育12 h,用抑制性削减杂交法克隆差异表达基因.随机挑取抑制性削减杂交所得克隆制备质粒,进行PCR扩增, 选取不同长度片断的产物,测序分析.结果发现1种骨骼肌结构蛋白基因(原肌球蛋白-4)表达下调,另发现2种凋亡相关的基因和2种功能不明基因的表达上调.结论①IL-1β/ IFN-γ下调骨骼肌结构蛋白基因,调节凋亡相关基因表达,推测可能是骨骼肌功能失调的原因之一;② 2种功能不明基因的表达为进一步研究骨骼肌功能失调的原因提供了新线索.     

Interferon-gamma inhibits aldehyde dehydrogenase bright cancer stem cells in the 4T1 mouse model of breast cancer

Background: Despite improvements in disease diagnosis, treatment, and prognosis, breast cancer is still a leading cause of cancer death for women. Compelling evidence suggests that targeting cancer stem cells (CSCs) have a crucial impact on overcoming the current shortcomings of chemotherapy and radiotherapy. In the present study, we aimed to study the effects of T cells and a critical anti-tumor cytokine, interferon-gamma (IFN-γ), on breast cancer stem cells.Methods: BALB/c mice and BALB/c nude...     

结核抗体检测联合结核感染T细胞斑点试验的临床诊断价值

目的 探讨结核抗体检测联合结核感染T细胞斑点试验(T-SPOT.TB)在结核病诊断中的应用价值。方法 选择2016年1月1日至2017年4月12日就诊于北京老年医院的961例结核病患者[结核病组;包括364例菌阳肺结核患者(通过细菌学诊断确诊)和597例菌阴肺结核患者(通过临床进行诊断)]和非结核病的1046例患者(对照组)。所有患者同时使用上海奥普生物医药有限公司及新加坡MP生物医学亚太私人有限公司生产的结核抗体金标试剂(分别为TB-DOT、ASSURE TB试剂盒)检测血清中的结核抗体;961例结核病组中的574例及1046例对照组中的664例患者同时使用T-SPOT.TB试剂盒和2种结核抗体金标试剂进行检测。对两组患者采用3种实验室技术进行检测或联合检测(包括串联与并联),对检测结果的敏感度、特异度进行统计学分析。结果 TB-DOT和ASSURE TB检测结核病组和对照组患者的敏感度和特异度分别为52.86%(508/961)、74.95%(784/1046)和45.99%(442/961)、76.00%(795/1046)。TB-DOT 和ASSURE TB对菌阳和菌阴肺结核患者检测的敏感度分别为64.84%(236/364)、62.09%(226/364)和45.56%(272/597)、36.18%(216/597);菌阳肺结核患者TB-DOT和ASSURE TB检测的敏感度均高于菌阴肺结核患者,差异均有统计学意义(χ ²值分别为60.99、33.69,P值均<0.05)。结核病组和对照组患者在2种结核抗体金标试剂和T-SPOT.TB试剂盒的串联联合检测中,敏感度为24.04%(138/574),但特异度达到89.91%(597/664);并联联合检测中,特异度为21.23%(141/664),但敏感度达到89.55%(514/574)。结核病组和对照组在ASSURE TB、TB-DOT和T-SPOT.TB 3种检测方法中,均为阳性和均为阴性两种谱型的构成比分别为24.04%(138/574)、10.09%(67/664)和10.45%(60/574)、21.23%(141/664),差异均有统计学意义(χ ²值分别为43.37和26.32,P值均<0.05)。 结论 两种结核抗体与T-SPOT.TB行串联联合检测能够提高检测特异度,并联联合检测能够提高检测敏感度;串联联合检测时,3种检测方法结果均为阳性和均为阴性两种谱型在临床上对结核病血清学诊断具有辅助诊断价值。     

Tuberculose oculaire

Despite extensive investigations, including the use of Interferon-gamma release assays (IGRA), the diagnosis of intraocular tuberculosis (TB) remains challenging. Ocular evidence of Mycobacterium tuberculosis in low endemic countries for TB is extremely rare, leading mostly to a TB-related ocular inflammation presumptive diagnosis. This present work aims: to highlights the main clinical patterns suggestive of ocular TB; and the latest recommended guidelines for diagnosing ocular TB to clarify interferon-gamma release assay (IGRA) contribution and accuracy to the management of intraocular TB and its diagnosis, in addition to other available diagnostic tools, such as tuberculin skin test, bacteriologic and histologic analysis from intra/extra ocular sample and radiographic investigations; to define the accuracy of these diagnostic tools according to the endemic TB prevalence; and finally to identify therapeutic strategies adapted to the main clinical presentations of ocular TB. Our review of the literature shows that management of suspected ocular TB differs significantly based on whether patients are from high or low TB prevalence countries since accuracy of chest X-ray, tuberculin skin test and IGRA is significantly different. Taking into account these discrepancies, distinct guidelines should be determined for managing patients with suspected ocular TB, taking into consideration home prevalence of TB-patients.     

脐血间充质干细胞移植治疗多发性肌炎/皮肌炎：Th细胞因子的变化

背景：近年来,应用干细胞治疗免疫性疾病已成为研究热点,国内外有关脐血间充质干细胞移植治疗多发性肌炎/皮肌炎的报道较少。目的：观察脐血间充质干细胞移植治疗多发性肌炎/皮肌炎患者血清干扰素γ、白细胞介素4、白细胞介素17水平变化,探讨Th细胞因子在多发性肌炎/皮肌炎发生发展中的免疫机制。方法：81例多发性肌炎/皮肌炎患者,其中44例为常规治疗组,给予糖皮质激素联合免疫抑制剂治疗,37例为脐血间充质干细胞移植组,静脉输注脐血间充质干细胞(3.5-5.2)×10⁷,用药方案与常规治疗组相同。随访治疗后1,3,6 个月肌酸激酶、肌力变化及治疗后3,6个月肺部影像学改变,并在治疗前及治疗后3,6个月检测移植组Th细胞因子水平。结果与结论：①两组治疗后1,3,6个月与治疗前比较肌酸激酶值明显下降、肌力评分明显增高(均P < 0.001);移植组治疗后各时间点肌酸激酶值较常规治疗组低、肌力评分较常规治疗组高(均P < 0.001)。②脐血间充质干细胞移植治疗能明显改善肺部影像学异常,且安全性好。③移植治疗后6个月干扰素γ水平显著升高,而白细胞介素4水平显著下降(均P < 0.01);移植治疗后 3,6 个月白细胞介素17水平显著下降(均P < 0.01)。④移植治疗后6个月白细胞介素4、白细胞介素17水平与肌酸激酶水平成正相关(r=0.467和0.488,均P < 0.05);干扰素γ水平与肌酸激酶水平无明显相关(r=0.213,P > 0.05)。结果表明给予糖皮质激素及免疫抑制剂治疗同时,联合脐血间充质干细胞移植治疗多发性肌炎/皮肌炎安全、有效,可调节多发性肌炎/皮肌炎患者免疫网络效应、改善免疫耐受。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

Inhibition of soluble epoxide hydrolase contributes to the anti-inflammatory effect of antimicrobial triclocarban in a murine model

The increasing use of the antimicrobial triclocarban (TCC) in personal care products (PCPs) has resulted in concern regarding environmental pollution. TCC is a potent inhibitor of soluble epoxide hydrolase (sEH). Inhibitors of sEH (sEHIs) are anti-inflammatory, anti-hypertensive and cardio-protective in multiple animal models. However, the in vivo effects anticipated from a sEHI have not been reported for TCC. Here we demonstrated the anti-inflammatory effects in vivo of TCC in a murine model. TCC was employed in a lipopolysaccharide (LPS)-challenged murine model. Systolic blood pressure, plasma levels of several inflammatory cytokines and chemokine, and metabolomic profile of plasma oxylipins were determined. TCC significantly reversed LPS-induced morbid hypotension in a time-dependent manner. TCC significantly repressed the increased release of inflammatory cytokines and chemokine caused by LPS. Furthermore, TCC significantly shifted the oxylipin profile in vivo in a time-dependent manner towards resolution of inflammation as expected from a sEHI. These results demonstrated that at the doses used TCC is anti-inflammatory in the murine model. This study suggests that TCC may provide some benefits in humans in addition to its antimicrobial activities due to its potent inhibition of sEH. It may be a promising starting point for developing new low volume high value applications of TCC. However these biological effects also caution against the general over use of TCC in PCPs.     

A multicentre evaluation of the accuracy and performance of IP-10 for the diagnosis of infection with M. tuberculosis

IP-10 has potential as a diagnostic marker for infection with Mycobacterium tuberculosis, with comparable accuracy to QuantiFERON-TB Gold In-Tube test (QFT-IT). The aims were to assess the sensitivity and specificity of IP-10, and to evaluate the impact of co-morbidity on IP-10 and QFT-IT. 168 cases with active TB, 101 healthy controls and 175 non-TB patients were included. IP-10 and IFN-γ were measured in plasma of QFT-IT stimulated whole blood and analyzed using previously determined algorithms. A subgroup of 48 patients and 70 healthy controls was tested in parallel with T-SPOT.TB IP-10 and QFT-IT had comparable accuracy. Sensitivity was 81% and 84% with a specificity of 97% and 100%, respectively. Combining IP-10 and QFT-IT improved sensitivity to 87% (p < 0.0005), with a specificity of 97%. T-SPOT.TB was more sensitive than QFT-IT, but not IP-10. Among non-TB patients IP-10 had a higher rate of positive responders (35% vs 27%, p < 0.02) and for both tests a positive response was associated with relevant risk factors. IFN-γ but not IP-10 responses to mitogen stimulation were reduced in patients with TB and non-TB infection. This study confirms and validates previous findings and adds substance to IP-10 as a novel diagnostic marker for infection with M. tuberculosis. IP-10 appeared less influenced by infections other than TB; further studies are needed to test the clinical impact of these findings.     

Interferon-γ and other inflammatory mediators in cardiomyocyte signaling during Chagas disease cardiomyopathy

Chagas disease cardiomyopathy(CCC), the main consequence of Trypanosoma cruzi(T.cruzi) infection, is an inflammatory cardiomyopathy that develops in up to 30% of infected individuals. The heart inflammation in CCC patients is characterized by a Th1 T cell-rich myocarditis with increased production of interferon(IFN)-γ, produced by the CCC myocardial infiltrate and detected at high levels in the periphery. IFN-γ has a central role in the cardiomyocyte signaling during both acute and chronic phases of T.cruzi infection. In this review, we have chosen to focus in its pleiotropic mode of action during CCC, which may ultimately be the strongest driver towards pathological remodeling and heart failure. We describe here the antiparasitic protective and pathogenic dual role of IFN-γ in Chagas disease.