Oxidation-specific epitopes are important targets of innate immunity

During the oxidation of LDL, a central pathophysiological component of atherogenesis, a wide variety of chemical and physical changes occur leading to the generation of oxidation-specific neoepitopes. These epitopes are not only immunogenic, leading to adaptive humoral responses, but are also a prominent target of multiple arcs of innate immunity. The pattern recognition receptors (PRRs) of innate immunity are germ line encoded, conserved by natural selection, and bind to pathogen-associated molecular patterns (PAMPs) common on multiple structures. However, it is not intuitive as to why they should recognize oxidation-specific neoepitopes. Yet it is clear that multiple macrophage scavenger receptors, which are classic PRRs, recognize oxidation-specific epitopes, such as those found on oxidized LDL (OxLDL). Other innate proteins, such as C-reactive protein, also bind to OxLDL. Natural antibodies (NAbs), the humoral arc of innate immunity, provide a nonredundant role in the first line of defence against pathogens, but are also believed to provide important homeostatic house-keeping functions against self-antigens. Our work demonstrates that oxidation-specific epitopes, as found on OxLDL, are a major target of NAbs. In this review, we will discuss the specific example of the prototypic NAb T15/E06, which is increased in atherosclerotic mice and mediates atheroprotection, and discuss the potential role of NAbs in atherogenesis, and in inflammation in general. We also review data that oxidation-specific epitopes are generated whenever cells undergo programmed cell death, forming a common set of PAMPs recognized by oxidation-specific PRRs on macrophages, NAbs and innate proteins. We present the hypothesis that oxidation-specific epitopes on apoptotic cells exerted evolutionary pressure for the conservation of these PRRs and also serve to maintain the expansion of a substantial proportion of NAbs directed to these stress-induced self-antigens.     

The effects of surgicel and bone wax hemostatic agents on bone healing: An experimental study

Background:

The biological effects of hemostatic agends on the physiological healing process need to be tested. The aim of this study was to assess the effects of oxidized cellulose (surgicel) and bone wax on bone healing in goats’ feet.

Materials and Methods:

Three congruent circular bone defects were created on the lateral aspects of the right and left metacarpal bones of ten goats. One defect was left unfilled and acted as a control; the remaining two defects were filled with bone wax and surgicel respectively. The 10 animals were divided into two groups of 5 animals each, to be sacrificed at the 3^rd and 5^th week postoperatively. Histological analysis assessing quality of bone formed and micro-computed tomography (MCT) measuring the quantities of bone volume (BV) and bone density (BD) were performed. The results of MCT analysis pertaining to BV and BD were statistically analyzed using two-way analysis of variance (ANOVA) and posthoc least significant difference tests.

Results:

Histological analysis at 3 weeks showed granulation tissue with new bone formation in the control defects, active bone formation only at the borders for surgicel filled defects and fibrous encapsulation with foreign body reaction in the bone wax filled defects. At 5 weeks, the control and surgicel filled defects showed greater bone formation; however the control defects had the greatest amount of new bone. Bone wax filled defects showed very little bone formation. The two-way ANOVA for MCT results showed significant differences for BV and BD between the different hemostatic agents during the two examination periods.

Conclusion:

Surgicel has superiority over bone wax in terms of osseous healing. Bone wax significantly hinders osteogenesis and induces inflammation.     

血管紧张素转换酶2基因转染对内皮细胞的保护作用

目的：探讨血管紧张素转换酶2（ACE2）基因转染对内皮细胞血凝素样氧化型低密度脂蛋白受体-1(LOX-1)表达的影响及意义。方法：实验包括体外实验与体内实验。体外实验,首先进行人脐静脉内皮细胞（HUVEC）的培养,然后应用蛋白质印迹法检测ACE2转染对血管紧张素II刺激HUVEC产生的LOX-1蛋白表达的影响。体内实验,首先建立载脂蛋白E基因敲除(ApoE-/-)小鼠动脉粥样硬化模型。然后将20只ApoE-/-小鼠随机分为ACE2组及增强型绿色荧光蛋白组（EGFP组）,每组10只。ACE2组经尾静脉注射ACE2的复制缺陷重组腺病毒（Ad-ACE2）(2.5×109 pfu/ml),EGFP组注射等量EGFP的复制缺陷重组腺病毒(Ad-EGFP)。注射一个月后处死动物,做腹主动脉的油红O及LOX-1表达的检测。结果：体内实验与体外实验均证实ACE2基因转染抑制了内皮细胞LOX-1的表达,体内实验中ACE2组斑块内脂质含量明显低于EGFP组水平。结论：ACE2通过抑制LOX-1的表达进而抑制了动脉粥样硬化斑块的进展。     

Consumption of cranberry beverage improved endogenous antioxidant status and protected against bacteria adhesion in healthy humans: a randomized controlled trial

Consumption of polyphenol-rich foods is associated with lower risk from many chronic diseases. We hypothesized that a single dose of cranberry beverage would improve indices of oxidative stress, inflammation, and urinary antibacterial adhesion activity in healthy humans. Six males and 6 females (18-35 years; body mass index, 19-25 kg/m²) consumed placebo, cranberry leaf extract beverage, or low-calorie cranberry juice cocktail (LCJC) once in a randomized, double-blind, placebo-controlled cross-over experimental design trial. The washout period between beverages was 1 week. Blood was collected 0, 2, 4, 8, and 24 hours after beverage consumption for measuring oxidative and inflammatory biomarkers. Urine was collected at 0, 0 to 3, 3 to 6, 6 to 9, 9 to 12, and 24 hours postintervention to assess antibacterial adhesion activity. Consumption of cranberry leaf extract beverage elevated (P < .05) blood glutathione peroxidase activity, whereas LCJC consumption increased (P < .05) glutathione concentrations and superoxide dismutase activity compared with placebo. Cranberry leaf extract beverage and LCJC consumption had no effect on the inflammatory biomarkers measured as compared with placebo. At 0 to 3 hours postconsumption, urine from participants who consumed cranberry beverages had higher (P < .05) ex vivo antiadhesion activity against P-fimbriated Escherichia coli compared with placebo. An acute dose of cranberry beverages improved biomarkers of antioxidant status and inhibition of bacterial adhesion in urine.     

Oxidized-low density lipoprotein in gingival crevicular fluid of patients with chronic periodontitis: a possible link to atherogenesis

Objective. To investigate a possible link between periodontitis and atherogenesis by examining the levels of anti-oxidized low density lipoprotien (ox LDL) and low density lipoprotien (LDL) in gingival crevicular fluid (GCF) and serum of healthy subjects and chronic periodontitis patients. Methods. Sixty male subjects (35–55 years) were grouped into 30 healthy individuals and 30 subjects with chronic periodontitis. Serum and GCF samples were obtained from each subject and were assessed for anti-ox LDL and LDL levels. Results. A significant difference (p < 0.001) was found between the anti-ox-LDL levels in GCF of healthy vs chronic periodontitis groups. Also the ratio of GCF anti-ox LDL to GCF LDL was significantly higher (p < 0.001) in chronic periodontitis patients as compared to the healthy group. Conclusions. A significant rise in ox LDL level in otherwise systemically healthy chronic periodontitis patients may put these subjects at an increased risk of developing atherosclerosis.     

尤瑞克林联合阿托伐他汀治疗对急性脑梗死患者临床疗效、氧化低密度脂蛋白及超敏C反应蛋白的影响

目的 观察尤瑞克林联合阿托伐他汀治疗急性动脉硬化性脑梗死临床疗效及对氧化低密度脂蛋白（ox LDL）、超敏C反应蛋白（hs CRP）的影响。方法 120例按TOAST分型为大动脉粥样硬化性且未进行溶栓取栓的急性脑梗死患者按随机分为对照组60例、观察组60例,两组给予常规治疗,包括抗血小板、神经保护剂、改善血液循环药物,对照组他汀类药物选择阿托伐他汀,20 mg/次,每晚1次;观察组给予阿托伐他汀20 mg,每晚1次,及尤瑞克林治疗,0.15 PNA,加入0.9%生理盐水 100 ml,静点每日1次,连续治疗2周。治疗前、治疗14天后分别进行脑卒中量表（NIHSS）评分,评估临床疗效。治疗前、治疗2周后采用方法测定血浆ox LDL、hs CRP含量。 结果 治疗2周后观察组ox LDL、hs CRP水平明显低于对照组(P＜0.01)。观察组和对照组治疗14天后 NIHSS 评分较治疗前明显降低(P＜0.05) ,观察组NIHSS 评分较对照组显著下降(P＜0.05) 。结论 阿托伐他汀联合尤瑞克林治疗未溶栓取栓的急性脑梗死患者可有效改善神经功能缺损,促进恢复神经功能,效果明显优于常规疗法。     

经皮氧分压联合血清ox-LDL预测下肢动脉硬化闭塞症介入治疗后再狭窄的临床价值

目的]探究经皮氧分压(TcPO₂)联合血清氧化型低密度脂蛋白(ox-LDL)预测下肢动脉硬化闭塞症(LASO)介入治疗后再狭窄的临床价值。 [方法]选取2020年1月—2021年6月在上海中医药大学附属岳阳中西医结合医院行介入治疗的113例LASO患者为观察对象,根据介入治疗后1年再狭窄发生情况将其分为未狭窄组(n＝79)和再狭窄组(n＝34),采用ELISA及相应试剂盒检测血清ox-LDL水平,运用激光多普勒血流仪测量TcPO₂,比较两组资料及TcPO₂、ox-LDL值,多因素Logistic回归模型研究LASO介入治疗后再狭窄的影响因素,采用Spearman检验进行相关性分析,ROC曲线评估TcPO₂、ox-LDL值预测LASO介入治疗后再狭窄的效能。 [结果]两组年龄、体质指数(BMI)、性别、饮酒、脑血管疾病史、冠心病史、病变血管支数、空腹血糖、同型半胱氨酸水平比较差异无统计学意义(P＞0.05)。与未狭窄组比较,再狭窄组吸烟、术后不规律用药、植入支架数量、ox-LDL和血尿酸水平明显增高(P＜0.05),TcPO₂明显降低(P＜0.05)。Logistic回归模型分析显示,吸烟、术后不规律用药、植入支架数量多、TcPO₂降低、ox-LDL和血尿酸增高为LASO介入治疗后再狭窄的危险因素(P＜0.05)。Spearman检验显示,ox-LDL与LASO介入治疗后再狭窄呈正相关(r＝0.513,P＜0.001),TcPO₂与其呈负相关(r＝－0.524,P＜0.001)。ROC曲线分析显示,TcPO₂＋ox-LDL预测LASO介入治疗后再狭窄时的效能(AUC＝0.802)高于各指标单独应用时,其预测的灵敏度和特异度为67.60%、94.90%,临界点为37.23 mmHg、5.31 mmol/L。 [结论]LASO介入治疗后再狭窄患者TcPO₂降低、ox-LDL增高,二者对LASO介入治疗后再狭窄有一定预测价值,TcPO₂与ox-LDL结合能更全面反映介入治疗后再狭窄情况。     

Overview of Chios Mastic Gum (Pistacia lentiscus) Effects on Human Health

Despite the remarkable development of the medical industry in the current era, herbal products with therapeutic potentials arise as attractive alternative treatments. Consequently, Chios mastiha, a natural, aromatic resin obtained from the trunk and brunches of the mastic tree, has recently gained increasing scientific interest due to its multiple beneficial actions. Chios mastiha is being exclusively produced on the southern part of Chios, a Greek island situated in the northern Aegean Sea, and its therapeutic properties have been known since Greek antiquity. There is now substantial evidence to suggest that mastiha demonstrates a plethora of favorable effects, mainly attributed to the anti-inflammatory and anti-oxidative properties of its components. The main use of mastiha nowadays, however, is for the production of natural chewing gum, although an approval by the European Medicines Agency for mild dyspeptic disorders and for inflammations of the skin has been given. The aim of this article is to summarize the most important data about the therapeutic actions of Chios mastiha and discuss future fields for its medical application.