Apelin attenuates streptozotocin-induced learning and memory impairment by modulating necroptosis signaling pathway

Apelin is a neuropeptide that plays an important role in neuronal protection. In this study, we investigated the effects of apelin intracerebroventricular administration on spatial learning and memory-related behaviors, and necroptosis signaling pathways in the hippocampus of streptozotocin (STZ) -injected rats. Apelin treatment was implemented following STZ-induced dementia for 15 days. After conducting a behavioral test (Morris Water Maze), the cellular and molecular aspects were examined to detect the apelin effect on the necroptosis signaling pathway. We demonstrated that STZ administration significantly slowed down the learning capability. However apelin treatment notably reversed this neuroinflammation induced behavioral impairment. Furthermore, molecular investigations showed that apelin treatment reduced the hippocampal RIP1, RIP3, and TNF-α level. Our results suggest that apelin treatment attenuates STZ-induced dementia. This effect may be mediated by inhibition of the necroptosis signaling pathway which seems to be associated with the ability of apelin to reduce central TNF-α level. This data provides evidence of the neuroprotective effect of apelin on STZ-induced learning and memory impairment and characterize some of the underlying mechanisms.     

Immunisation with the BCG and DTPw vaccines induces different programs of trained immunity in mice

In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes.     

Interleukin-11 Overexpression and M2 Macrophage Density are Associated with Angiogenic Activity in Proliferative Diabetic Retinopathy

ABSTRACT

Purpose

To investigate the expression of IL-11 and its receptor IL-11Rα and to quantify density of CD163⁺ M2 macrophages in proliferative diabetic retinopathy (PDR).     

Magnesium lithospermate B acts against dextran sodiumsulfate-induced ulcerative colitis by inhibiting activation of the NRLP3/ASC/Caspase-1 pathway

This study aimed to observe the therapeutic effects of magnesium lithospermate B on acute and chronic colitis induced by dextran sodiumsulfate (DSS) and the role of inflammasome complex (NOD-like receptor protein, NLRP; apoptosis-associated speck-like protein containing, ASC; caspase-1). Establishment of acute and chronic colitis models were by using 5% DSS oral administration in BALB/C male mice. Magnesium lithospermate B (240 mg/kg body weight) was given by subcutaneous injection. Samples were collected for biomarker assay, histological examination, immunohistochemical evaluation and western blot. There was obvious increase in TNF-α level and NLPR3, ASC, and caspase-1 expressions in acute and chronic colitis groups compared with the normal control. Significant decrease of the tumor necrosis factor-α level and the expressions of NLPR3, ASC, and caspase-1 were observed after treatment with magnesium lithospermate B. This study showed that magnesium lithospermate B could be used to treat acute and chronic colitis by inhibiting the activation of the NLRP3/ASC/Caspase-1 pathway.     

The functional role of platelets in the regulation of angiogenesis

Functionally, platelets are primarily recognized as key regulators of thrombosis and hemostasis. Upon vessel injury, the typically quiescent platelet interacts with subendothelial matrix to regulate platelet adhesion, activation and aggregation, with subsequent induction of the coagulation cascade forming a thrombus. Recently, however, newly described roles for platelets in the regulation of angiogenesis have emerged. Platelets possess an armory of pro- and anti-angiogenic proteins, which are actively sequestered and highly organized in α-granule populations. Platelet activation facilitates their release, eliciting potent angiogenic responses through mechanisms that appear to be tightly regulated. In conjunction, the release of platelet-derived phospholipids and microparticles has also earned merit as synergistic regulators of angiogenesis. Consequently, platelets have been functionally implicated in a range of angiogenesis-dependent processes, including physiological roles in wound healing, vascular development and blood/lymphatic vessel separation, whilst facilitating aberrant angiogenesis in a range of diseases including cancer, atherosclerosis and diabetic retinopathy. Whilst the underlying mechanisms are only starting to be elucidated, significant insights have been established, suggesting that platelets represent a promising therapeutic strategy in diseases requiring angiogenic modulation. Moreover, anti-platelet therapies targeting thrombotic complications also exert protective effects in disorders characterized by persistent angiogenesis.     

一测多评法同时测定不同采收期杜仲叶中4种黄酮

目的建立一测多评法同时测定不同采收期杜仲叶中槲皮素-3-O-α-L-阿拉伯糖-(1→2)-β-D-葡萄糖苷、芦丁、异槲皮苷和紫云英苷的含有量。方法杜仲叶50%甲醇提取物的分析采用Thermo BDS HYPERSIL C18色谱柱(250 mm×4.6 mm,5μm);流动相乙腈-0.1%磷酸溶液,梯度洗脱;体积流量1.0 mL/min;柱温30℃;检测波长360 nm。以槲皮素-3-O-α-L-阿拉伯糖-(1→2)-β-D-葡萄糖苷为内标,计算芦丁、异槲皮苷、紫云英苷的相对校正因子,计算其他3种成分的相对校正因子,再测定其含有量。结果槲皮素-3-O-α-L-阿拉伯糖-(1→2)-β-D-葡萄糖苷、芦丁、异槲皮苷、紫云英苷分别在5.37~161.00(r=0.999 9)、0.43~12.84(r=0.999 9)、1.58~47.33(r=0.999 8)、0.42~12.65(r=0.999 7)μg/mL范围内线性关系良好,平均加样回收率分别为97.27%、96.10%、95.30%、96.72%,RSD分别为1.90%、1.12%、1.07%、1.37%。一测多评法所得结果接近于外标法。结论该方法准确稳定,重复性好,可用于杜仲叶的质量控制。     

妇炎舒胶囊联合抗生素治疗慢性盆腔炎疗效分析

目的观察中药妇炎舒胶囊联合盐酸左氧氟沙星片和甲硝唑片治疗慢性盆腔炎患者的疗效和相关炎性因子的影响。方法收取118例湿热瘀结型慢性盆腔炎的患者,随机分为实验组(A组)和对照组(B组)各59例。A组给予妇炎舒胶囊56 d,B组妇炎舒胶囊模拟剂56 d,两组均服用盐酸左氧氟沙星片+甲硝唑片用药14 d。患者服药56 d后观察临床有效率及治疗前后血清中肿瘤坏死因子-α(Tumor necrosis factor,TNF-α),干扰素-γ(Interferon,IFN-γ)因子含量的变化;随访1个月经周期后观察者复发率及慢性盆腔痛情况。结果(1)A组中医证候积分有效率明显高于B组,且差异有统计学意义(P<0.01)。(2)治疗后A组患者外周血中TNF-α和IFN-γ的含量明显低于B组,具有显著统计学差异(P<0.01)。(3)A组随访复发率(10.17%vs 96.61%)和后遗盆腔痛(18.64%vs 86.44%)均显著低于B组(P<0.01)。结论中药妇炎舒胶囊联合抗生素治疗湿热瘀结型慢性盆腔炎疗效显著,并能够降低慢性盆腔炎的复发率和慢性盆腔痛,并能通过适当降低外周血中TNF-α、IFN-γ等炎性因子的形成,起到治疗作用。     

Plasma matrix metalloproteinase 7, CC-chemokine ligand 18, and periostin as markers for pulmonary sarcoidosis

BackgroundSome patients with sarcoidosis experience worsening of pulmonary lesions. However, no biomarker has been identified that reflects pulmonary disease status in sarcoidosis. We investigated the usefulness of potential markers of pulmonary fibrosis in patients with sarcoidosis.MethodsPlasma matrix metalloproteinase 7 (MMP-7), CC-chemokine ligand 18 (CCL-18), and periostin levels were evaluated in 60 patients with sarcoidosis and 30 healthy controls; bronchoalveolar lavage fluid levels were analyzed in 22 patients with sarcoidosis. To determine the usefulness of these markers, we explored potential correlations between these markers and sarcoidosis clinical characteristics.ResultsPlasma MMP-7, CCL-18, and periostin concentrations were significantly higher in patients with sarcoidosis than those in healthy controls. MMP-7 concentrations in plasma and bronchoalveolar lavage fluid were higher in patients with sarcoidosis with parenchymal infiltration than in those without lung lesions. Moreover, MMP-7 concentration was negatively correlated with pulmonary function.ConclusionAmong these novel biomarkers, MMP-7 most precisely reflected pulmonary sarcoidosis disease status and thus, might be useful for diagnosing and evaluating sarcoidosis, particularly in patients with pulmonary parenchymal lesions.