Low testosterone levels are inversely correlated with carotid artery plaque formation in elderly women

Objective To study the relationship between serum testosterone levels and the plaque formation of the carotid artery in a population-based cohort of independently living healthy women above 60 years of age. Methods Analysis of the healthy elders from a population-based cohort study in 9 communities of Beijing. Carotid intima-media thickness and atherosclerotic plaques were determined ultrasonographically. Serum testosterone levels were measured by immunoassay. The data were analyzed with ANOVA and logistic regression analysis. Results There was an inverse correlation between testosterone and plaque formation in old females（P〈0.01）, while no association was found in males. Female with testosterone levels in the lowest quartile （〈0.49 nmol/L） had more risk of plaque formation（OR=3.805, P〈0.01） after adjusted with age and other traditional factors of atherosclerosis. Conclusion Testosterone concentrations are negatively associated with carotid artery atherosclerosis in old women in Beijing, experimental and prospective studies are needed to determine the possible therapeutic role of testosterone in atherosclerosis.     

Exercise-induced enhancement of insulin sensitivity is associated with accumulation of M2-polarized macrophages in mouse skeletal muscle

Exercise enhances insulin sensitivity in skeletal muscle, but the underlying mechanism remains obscure. Recent data suggest that alternatively activated M2 macrophages enhance insulin sensitivity in insulin target organs such as adipose tissue and liver. Therefore, the aim of this study was to determine the role of anti-inflammatory M2 macrophages in exercise-induced enhancement of insulin sensitivity in skeletal muscle. C57BL6J mice underwent a single bout of treadmill running (20 m/min, 90 min). Twenty-four hours later, ex vivo insulin-stimulated 2-deoxy glucose uptake was found to be increased in plantaris muscle. This change was associated with increased number of CD163-expressing macrophages (i.e. M2-polarized macrophages) in skeletal muscle. Systemic depletion of macrophages by pretreatment of mice with clodronate-containing liposome abrogated both CD163-positive macrophage accumulation in skeletal muscle as well as the enhancement of insulin sensitivity after exercise, without affecting insulin-induced phosphorylation of Akt and AS160 or exercise-induced GLUT4 expression. These results suggest that accumulation of M2-polarized macrophages is involved in exercise-induced enhancement of insulin sensitivity in mouse skeletal muscle, independently of the phosphorylation of Akt and AS160 and expression of GLUT4.     

巨噬细胞极化及其在临床疾病治疗中的潜在应用价值

巨噬细胞(macrophages)是免疫系统的重要组成部分,在机体免疫调控和组织修复中起着核心作用.巨噬细胞是一种可塑性细胞,在不同刺激下可以极化为功能不同的多种亚型,不同极化状态的巨噬细胞在疾病发展和预后中发挥着重要作用.对巨噬细胞极化的深入研究有助于探索预防和治疗疾病的新策略.本文总结了不同微环境信号刺激下巨噬细胞的不同极化表型及其主要功能,并重点介绍了巨噬细胞极化在肿瘤、动脉粥样硬化和2型糖尿病中的作用以及以巨噬细胞极化为靶标的临床疾病治疗策略.     

SPP1在头颈部鳞状细胞癌的免疫浸润及临床相关性分析

探讨分泌型磷蛋白1 (Secreted Phosphoprotein 1,SPP1)在头颈部鳞状细胞癌(Head and neck squamous cell carcinoma, HNSC)中与免疫浸润及临床的相关性,明确SPP1在HNSC预后和个体化治疗中的潜在价值。使用癌症基因组图谱(The Cancer Genome Atlas, TCGA)HNSC数据分析SPP1表达。使用来自TCGA的临床生存数据评估SPP1的临床预后价值。使用R语言的clusterProfiler包进行SPP1相关的富集分析。使用R语言的CIBERSORT函数评估22种肿瘤浸润免疫细胞在HNSC中的浸润情况,分析肿瘤浸润免疫细胞与SPP1表达之间的关联。差异表达分析发现SPP1在HNSC中高表达(P<0.001),临床相关性分析发现SPP1表达与T分期(P=0.001)、临床分期(P=0.013)相关,SPP1高表达患者的总生存期明显短于低表达患者(P=0.020 4)。基因富集分析发现SPP1在HNSC中与免疫学功能及免疫相关通路有关联。肿瘤浸润免疫细胞分析发现在高SPP1表达组中,M2巨噬细胞(...     

Trichinella spiralis infection ameliorated diet-induced obesity model in mice

Obesity is an increasingly prevalent disease worldwide, and genetic and environmental factors are known to regulate the development of obesity and associated metabolic diseases. Emerging studies indicate that innate and adaptive immune cell responses in adipose tissue play critical roles in the regulation of metabolic homeostasis. Parasitic helminths are the strongest natural inducers of type 2 inflammatory responses, and several studies have revealed that helminth infections inversely correlate with metabolic syndrome. Hence, this study investigated whether helminth infections could have preventative effects on high fat diet-induced obesity. Female C57BL/6 mice were maintained on either a low fat diet (LFD, 10% fat) or a high fat diet (HFD, 60% fat) for 6 weeks after Trichinella spiralis infection. The mice were randomly divided into four groups and were fed a normal diet, LFD, LFD after T. spiralis infection (Inf + LFD), a high fat diet (HFD), or HFD after T. spiralis infection (HFD + inf). All groups were assayed for body weight, food efficiency ratio (FER), total body weight gain (g)/total food intake amount (g) fat weight, and blood biochemical parameters. Our data indicate that the HFD + inf group significantly reduced body weight gain, fat mass, total cholesterol, and FER. Analysis of immune cell composition by flow cytometry revealed that T. spiralis promoted strong decreases in proinflammatory adipose macrophages (F4/80⁺CD11c⁺) and T cells. The alterations in microbiota from fecal samples of mice were analyzed, which showed that T. spiralis infection decreased the ratio of Firmicutes to Bacteriodetes, thereby restoring the previously increased ratio of Firmicutes to Bacteriodetes in HFD-fed mice. Moreover, elimination of T. spiralis retained the protective effects in the HFD-fed obese mice whereas flubendazole (FLBZ) treatment increased levels of the families Lachnospiraceae and Ruminococcaceae. In summary, we provided novel data suggesting that helminth infection protects against obesity and the protection was closely related to M2 macrophage proliferation, an inhibiting proinflammatory response. In addition, it alters the microbiota in the gut.     

SPION primes THP1 derived M2 macrophages towards M1-like macrophages

Potentially, cellular iron regulates functional plasticity in macrophages yet; interaction of functionally polarized macrophages with iron-oxide nanoparticles has never been studied. We found that monocyte differentiation alters cellular ferritin and cathepsin L levels and induces functional polarization in macrophages. Iron in super paramagnetic iron-oxide nanoparticle (SPION) induces a phenotypic shift in THP1 derived M2 macrophages towards a high CD86+ and high TNF α+ macrophage subtype. This phenotypic shift was accompanied by up-regulated intracellular levels of ferritin and cathepsin L in M2 macrophages, which is a characteristic hallmark of M1 macrophages. Atherogenic oxysterols reduce phagocytic activity in macrophage subtypes, and thus these cells may escape detection by iron-oxide nanoparticles (INPs) in-vivo.     

The homologies of the lorisoid internal carotid artery system

The development of the “internal carotid” arterial system of the lesser galago (Galago senegalensis senegalensis)is described. The first artery to be formed is a typical promontory artery which runs through the middle-ear cavity and gives off the stapedial artery. It terminates in the cranial cavity by dividing into the middle cerebral, anterior cerebral, and two ophthalmic arteries. It is accompanied by the internal carotid nerve. A medially directed artery to the external carotid rete arises from the commencement of the promontory artery and joins the caudal end of the rete, whose cranial end lies in the foramen lacerum. As the promontory artery enters the cranial cavity, it communicates with the cranial end of the rete. The promontory artery, between the origin of the artery to the rete and its connection with the rete, becomes narrowed and eventually disappears. Thus the internal carotid artery is formed from the commencement of the promontory artery, the artery to the rete, the external carotid rete, and the terminal intracranial part of the promontory artery. The relationships of the artery to the rete indicate that it is the homologue of the human ascending pharyngeal artery.     

miR-451对肿瘤相关巨噬细胞极化抑制胶质瘤进展的调控作用

目的 研究miR-451对胶质瘤进展的影响及肿瘤相关巨噬细胞（TAMs）极化在其中的调控作用。方法 将THP-1细胞诱导分化为M0/M1/M2型巨噬细胞,将M0型巨噬细胞与U251细胞共培养获得TAM,检测miR-451、磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/AKT)及M1/M2型巨噬细胞标志物表达。将TAM分为过表达miR-451组、过表达对照组、过表达miR-451联合PI3K激动剂组、过表达对照联合PI3K激动剂组。TAM进行相应处理后,与U251细胞共培养。将U251细胞分为miR-451-TAM共培养组、miR-NC-TAM共培养组、miR-451-TAM联合Recilisib共培养组,miR-NC-TAM联合Recilisib共培养组。检测共培养后TAM中miR-451、PI3K/AKT及M2型巨噬细胞标志物表达量。检测共培养后U251细胞存活率、EdU阳性率及迁移/侵袭细胞数。结果 TAM趋向于向M2型极化。过表达miR-451后,TAM中miR-451(t=6.027,P=0.002)表达量升高,CD206(t=13.723, P<0.001)、 Arg1(t=16.862, P<0.001)、 Ym1(t=10.263, P<0.001)、 Fizz1(t=9.779, P<0.001)、 PI3K mRNA(t=6.359, P=0.001)、 PI3K蛋白（t=8.262, P<0.001）、 AKT mRNA(t=4.738, P=0.005)、AKT蛋白（t=12.134, P<0.001）表达量降低,U251细胞存活率（t=5.186, P=0.004）、 EdU阳性率（t=6.221,P=0.002）降低,迁移细胞数（t=5.888,P=0.002）和侵袭细胞数（t=5.292,P=0.003）减少。结论 miR-451能够抑制胶质瘤中TAM向M2型极化,miR-451可能通过PI3K/AKT通路抑制胶质瘤细胞的增殖和转移。