Leptin favors Th17/Treg cell subsets imbalance associated with allergic asthma severity

BackgroundObesity has often been associated with severe allergic asthma (AA). Here, we analyzed the frequency of different circulating CD4⁺T‐cell subsets from lean, overweight and obese AA patients.MethodsMononuclear cells from peripheral blood were obtained from 60 AA patients and the frequency of different CD4⁺T‐cell subsets and type 1 regulatory B cells (Br1) was determined by cytometry. The effect of obese‐related leptin dose on cytokine production and Treg cell function in AA‐derived CD4⁺ T cell cultures was evaluated by ELISA and 3H thymidine uptake, respectively. Leptin levels were quantified in the plasma by ELISA. According to the BMI, patients were stratified as lean, overweight and obese.ResultsAA severity, mainly among obese patients, was associated with an expansion of hybrid Th2/Th17 and Th17‐like cells rather than classic Th2‐like cells. On the other hand, the frequencies of Th1‐like, Br1 cells and regulatory CD4⁺ T‐cell subsets were lower in patients with severe AA. While percentages of the hybrid Th2/Th17 phenotype and Th17‐like cells positively correlated with leptin levels, the frequencies of regulatory CD4⁺ T‐cell subsets and Br1 cells negatively correlated with this adipokine. Interestingly, the obesity‐related leptin dose not only elevated Th2 and Th17 cytokine levels, but also directly reduced the Treg function in CD4⁺ T cell cultures from lean AA patients.ConclusionIn summary, our results indicated that obesity might increase AA severity by favoring the expansion of Th17‐like and Th2/Th17 cells and decreasing regulatory CD4⁺T cell subsets, being adverse effects probably mediated by leptin overproduction.     

白细胞介素6(IL-6)和IL-8mRNA在变应原诱导的鼻粘膜晚期反应标本的表达

目的测定IL-6和IL-8变应原诱导的鼻粘膜晚期反应标本中mRNA的表达。方法采用原位杂交技术,测定变应原诱导的10例变态反应性鼻炎病人的鼻粘膜标本表达IL-6和IL-8mRNA阳性细胞数。结果在10例标本中,2种细胞因子的阳性表达率分别为9/10和10/10。与对照相比,变应原诱导的鼻粘膜标本表达IL-6和IL-8mRNA阳性细胞数明显增加(P＜0.05和P＜0.01)。结论IL-6和IL-8mRNA表达增加可作为变态反应性鼻炎晚期的标志。     

3种品系大鼠对灯盏花素所致 被动皮肤过敏差异性研究

目的:比较F344,SD,Wistar 3种品系大鼠对灯盏花素诱导的被动皮肤过敏(passive cutaneous anaphylaxis,PCA)反应的差异性。方法:取3种品系大鼠随机分为阴性对照组、天花粉组、灯盏花素组。采用sc给药方式,分别给予各组动物不同的药物,进行大鼠同种或大鼠-小鼠异种PCA试验,检测给予灯盏花素后动物皮肤蓝斑吸光度(A),比较药物对F344,SD,Wistar 3种品系大鼠的A变化率。结果:大鼠同种PCA试验显示:3种品系大鼠注射灯盏花素25 mg.kg-1致敏后,F344大鼠皮肤蓝斑A为0.064±0.005 7,明显升高(P<0.05),SD,Wistar大鼠PCA反应均为阴性。大鼠-小鼠异种PCA试验显示:注射F344大鼠抗血清后,小鼠异种PCA反应为阳性,A为0.10±0.01(P<0.05),注射SD,Wistar大鼠抗血清后,反应均为阴性。结论:2种试验方法结果均显示,3种品系大鼠对灯盏花素的敏感性存在差异,其中以F344大鼠最为敏感。     

电针对健康家兔体表胃电图和17肽胃泌素的影响

本文观察到，电针足三里及刺激中脑导水管周围灰质（ＰＡＧ），对健康家兔胃电（ＥＧＧ）均呈抑制性效应，并使血清胃泌素（Ｇ１７）含量减少。损毁ＰＡＧ后，电针足三里的效应消失；静脉注射α受体阻断剂酚妥拉明（Ｒｅｇｉｔｉｎｅ）和β受体阻断剂心得安（Ｐｒｏｐｒａｎｏｌｏｌ）阻断交感肾上腺素能神经的功能后，对电针和电刺激的效应没有影响；静脉注射阿托品（Ａｔｒｏｐｉｎｅ）也不能遏止电针和电刺激的效应；切断双侧颈部迷走神经后，电针足三里及电刺激ＰＡＧ的效应均减弱，甚或消失。说明电针足三里抑制ＥＧＧ和降低血清Ｇ１７含量的效应是通过激发ＰＡＧ的活动而实现的，迷走神经非胆碱能纤维是其主要传出途径。     

Ethnopharmacological in vitro studies on Austria's folk medicine—An unexplored lore in vitro anti-inflammatory activities of 71 Austrian traditional herbal drugs

Ethnopharmacological relevance

In Austria, like in most Western countries, knowledge about traditional medicinal plants is becoming scarce. Searching the literature concerning Austria's ethnomedicine reveals its scant scientific exploration.Aiming to substantiate the potential of medicinal plants traditionally used in Austria, 63 plant species or genera with claimed anti-inflammatory properties listed in the VOLKSMED database were assessed for their in vitro anti-inflammatory activity.

Material and methods

71 herbal drugs from 63 plant species or genera were extracted using solvents of varying polarities and subsequently depleted from the bulk constituents, chlorophylls and tannins to avoid possible interferences with the assays. The obtained 257 extracts were assessed for their in vitro anti-inflammatory activity. The expression of the inflammatory mediators E-selectin and interleukin-8 (IL-8), induced by the inflammatory stimuli tumor necrosis factor alpha (TNF-α) and the bacterial product lipopolysaccharide (LPS) was measured in endothelial cells. The potential of the extracts to activate the nuclear factors PPARα and PPARγ and to inhibit TNF-α-induced activation of the nuclear factor-kappa B (NF-κB) in HEK293 cells was determined by luciferase reporter gene assays.

Results

In total, extracts from 67 of the 71 assessed herbal drugs revealed anti-inflammatory activity in the applied in vitro test systems. Thereby, 30 could downregulate E-selectin or IL-8 gene expression, 28 were strong activators of PPARα or PPARγ (inducing activation of more than 2-fold at a concentration of 10 µg/mL) and 21 evoked a strong inhibition of NF-κB (inhibition of more than 80% at 10 µg/mL).

Conclusion

Our research supports the efficacy of herbal drugs reported in Austrian folk medicine used for ailments associated with inflammatory processes. Hence, an ethnopharmacological screening approach is a useful tool for the discovery of new drug leads.     

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。     

补肺汤对肺纤维化大鼠血清INF-γ IL-4表达水平影响的实验研究

目的：观察补肺汤对肺纤维化大鼠血清IFN-γ、IL-4表达水平的影响,探讨补肺汤对肺纤维化的治疗作用及可能的作用机制。方法：96只SD健康大鼠,随机分为4组（每组各24只）：空白对照组、模型对照组、强的松阳性对照组、补肺汤治疗组。模型对照组和治疗组气管内注射博莱霉素诱导肺纤维化模型,正常对照组在相同条件下给予生理盐水。补肺汤治疗组和强的松阳性对照组分别给予补肺汤流浸膏（2.1g/200g）及强的松片与生理盐水混合制剂（6.3mg/kg）灌胃,其余两组每天给予生理盐水（1mL/100g）灌胃。各组分别于造模后第7、14、28天各处死8只大鼠,取大鼠血清和肺组织。肺组织病理切片HE染色和MASSON染色观察病理变化和肺纤维化分级情况,ELISA法测定血清中INF-γ、IL-4含量的变化。结果：与模型对照组比较,补肺汤治疗组和强的松阳性对照组大鼠各个时期的血清IFN-γ表达明显增高（P〈0.05）;强的松阳性对照组大鼠血清IL-4在各个时期的表达降低明显（P〈0.05）,而补肺汤治疗组在第28天降低明显（P〈0.05）。结论：补肺汤肺纤维化的形成有较好的治疗作用,其机制可能是通过促进血清中IFN-γ的分泌,抑制IL-4的分泌,从而调节了Th1/Th2细胞因子失衡来实现的。     

戊型肝炎肝衰竭患者的血生化指标及血清IL-22表达水平研究

目的研究由HEV感染引起的肝衰竭(hepatic failure,HF)患者肝功能指标特征及血清IL-22水平。方法回顾性分析132例戊型肝炎(戊肝)HF病例资料,按照是否有HBV感染分为混合感染HF组和单纯戊肝HF组,比较2组肝功指标、IL-22、IL-6以及IFN-γ水平。以普通戊肝组和健康体检组作对照,比较4组IL-22、IL-6及IFN-γ水平。结果混合感染HF组ALT、TBIL水平高于单纯戊肝HF组(P均0.05),PA水平低于单纯戊肝HF组(P0.05)。在IL-22水平方面,戊肝患者均高于健康对照者,混合感染HF组最高,普通戊肝组最低。在IL-6水平方面,HF患者均高于健康对照者,且混合感染HF组最高(P均0.05),但是普通戊肝组与健康对照组差异无统计学意义。4组IFN-γ差异无统计学意义。结论与单纯戊肝HF患者相比,混合感染HF组肝功能损害程度更严重。戊肝患者IL-22、IL-6水平升高,发生HF时明显升高,合并HBV感染时更高。     

Timing and completion of puberty in female mice depend on estrogen receptor alpha-signaling in kisspeptin neurons

Puberty onset is initiated by activation of neurons that secrete gonadotropin-releasing hormone (GnRH). The timing and progression of puberty may depend upon temporal coordination of two opposing central mechanisms--a restraint of GnRH secretion before puberty onset, followed by enhanced stimulation of GnRH release to complete reproductive maturation during puberty. Neuronal estrogen receptor α (ERα) has been implicated in both controls; however, the underlying neural circuits are not well understood. Here we test whether these mechanisms are mediated by neurons that express kisspeptin, a neuropeptide that modulates GnRH neurosecretion. Strikingly, conditional ablation of ERα in kisspeptin neurons results in a dramatic advancement of puberty onset in female mice. Furthermore, subsequent pubertal maturation is arrested in these animals, as they fail to acquire normal ovulatory cyclicity. We show that the temporal coordination of juvenile restraint and subsequent pubertal activation is likely mediated by ERα in two separate kisspeptin neuronal populations in the hypothalamus.