A polysaccharide, CSL-0.1, was isolated from the medicinal lichen, Usnea longissima. CSL-0.1 was a neutral rhamnose-containing glucogalactomannan with a molecular weight of 7.86 × 10⁴ Da. The polysaccharide had a core mannan structure with (1 → 6)-α-d-Manp units as the main chain and was substituted at the O-2 positions with side chains containing (1 → 2)-α-d-Manp residue, [3)-α-Glcp(1 → 4)-α-Glcp(1→] and 6-O-substituted β-d-Galf units. 2-O- and 2,3-di-O-substituted Rhap units. The effects of CSL-0.1 on intestinal immunity and antioxidant activity were evaluated. CSL-0.1 increased the spleen and thymus indices in a dose-dependent manner and conferred immunomodulation on reversing the Th1/Th2-related cytokine imbalance in cyclophosphamide (CP)-induced immunosuppressed mice. CSL-0.1 could also enhance the levels of secretory immunoglobulin A in CP-injected mice. Additionally, the antioxidant levels in the liver and intestine of the mice were increased 20%-50% after intragastric injection by CSL-0.1.

2020-11-06·Circulation Research1区 · 医学

Apo AI Nanoparticles Delivered Post Myocardial Infarction Moderate Inflammation

1区 · 医学

Article

作者: Reddy, Medini ; Carey, Andrew L. ; Heywood, Sarah E. ; Siebel, Andrew L. ; Lancaster, Graeme L. ; Murphy, Andrew J. ; Kingwell, Bronwyn A. ; Drew, Brian G. ; Richart, Adele L. ; Navdaev, Alexei V. ; Didichenko, Svetlana A. ; Khalaji, Mina ; Natoli, Alaina L.

Rationale:Decades of research have examined immune-modulatory strategies to protect the heart after an acute myocardial infarction and prevent progression to heart failure but have failed to translate to clinical benefit.Objective:To determine anti-inflammatory actions of n-apo AI (Apo AI nanoparticles) that contribute to cardiac tissue recovery after myocardial infarction.Methods and Results: Using a preclinical mouse model of myocardial infarction, we demonstrate that a single intravenous bolus of n-apo AI (CSL111, 80 mg/kg) delivered immediately after reperfusion reduced the systemic and cardiac inflammatory response. N-apo AI treatment lowered the number of circulating leukocytes by 30±7% and their recruitment into the ischemic heart by 25±10% (all P <5.0×10 −2 ). This was associated with a reduction in plasma levels of the clinical biomarker of cardiac injury, cardiac troponin-I, by 52±17% ( P =1.01×10 −2 ). N-apo AI reduced the cardiac expression of chemokines that attract neutrophils and monocytes by 60% to 80% and lowered surface expression of integrin CD11b on monocytes by 20±5% (all P <5.0×10 −2 ). Fluorescently labeled n-apo AI entered the infarct and peri-infarct regions and colocalized with cardiomyocytes undergoing apoptosis and with leukocytes. We further demonstrate that n-apo AI binds to neutrophils and monocytes, with preferential binding to the proinflammatory monocyte subtype and partially via SR-BI (scavenger receptor BI). In patients with type 2 diabetes, we also observed that intravenous infusion of the same n-apo AI (CSL111, 80 mg/kg) similarly reduced the level of circulating leukocytes by 12±5% (all P <5.0×10 −2 ). Conclusions:A single intravenous bolus of n-apo AI delivered immediately post–myocardial infarction reduced the systemic and cardiac inflammatory response through direct actions on both the ischemic myocardium and leukocytes. These data highlight the anti-inflammatory effects of n-apo AI and provide preclinical support for investigation of its use for management of acute coronary syndromes in the setting of primary percutaneous coronary interventions.

2020-04-01·Anesthesiology1区 · 医学

Reconstituted High-density Lipoprotein Therapy Improves Survival in Mouse Models of Sepsis

1区 · 医学

Article

作者: Meilhac, Olivier ; Planesse, Cynthia ; Bringart, Matthieu ; Viranaïcken, Wildriss ; Genève, Claire ; Duranteau, Jacques ; Zappella, Nathalie ; Couret, David ; Denamur, Erick ; Louedec, Liliane ; Montravers, Philippe ; Yong-Sang, Jennyfer ; Tanaka, Sébastien

AbstractBackgroundHigh-density lipoproteins exert pleiotropic effects including antiinflammatory, antiapoptotic, and lipopolysaccharide-neutralizing properties. The authors assessed the effects of reconstituted high-density lipoproteins (CSL-111) intravenous injection in different models of sepsis.MethodsTen-week-old C57BL/6 mice were subjected to sepsis by cecal ligation and puncture or intraperitoneal injection of Escherichia coli or Pseudomonas aeruginosa pneumonia. CSL-111 or saline solution was administrated 2 h after the sepsis. Primary outcome was survival. Secondary outcomes were plasma cell-free DNA and cytokine concentrations, histology, bacterial count, and biodistribution.ResultsCompared with saline, CSL-111 improved survival in cecal ligation and puncture and intraperitoneal models (13 of 16 [81%] survival rate vs. 6 of 16 [38%] in the cecal ligation and puncture model; P = 0.011; 4 of 10 [40%] vs. 0 of 10 [0%] in the intraperitoneal model; P = 0.011). Cell-free DNA concentration was lower in CSL-111 relative to saline groups (68 [24 to 123] pg/ml vs. 351 [333 to 683] pg/ml; P < 0.001). Mice injected with CSL-111 presented a decreased bacterial count at 24 h after the cecal ligation and puncture model both in plasma (200 [28 to 2,302] vs. 2,500 [953 to 3,636] colony-forming unit/ml; P = 0.021) and in the liver (1,359 [360 to 1,648] vs. 1,808 [1,464 to 2,720] colony-forming unit/ml; P = 0.031). In the pneumonia model, fewer bacteria accumulated in liver and lung of the CSL-111 group. CSL-111–injected mice had also less lung inflammation versus saline mice (CD68+ to total cells ratio: saline, 0.24 [0.22 to 0.27]; CSL-111, 0.07 [0.01 to 0.09]; P < 0.01). In all models, no difference was found for cytokine concentration. 111Indium bacterial labeling underlined a potential hepatic bacterial clearance possibly promoted by high-density lipoprotein uptake.ConclusionsCSL-111 infusion improved survival in different experimental mouse models of sepsis. It reduced inflammation in both plasma and organs and decreased bacterial count. These results emphasized the key role for high-density lipoproteins in endothelial and organ protection, but also in lipopolysaccharide/bacteria clearance. This suggests an opportunity to explore the therapeutic potential of high-density lipoproteins in septic conditions.Editor’s PerspectiveWhat We Already Know about This TopicWhat This Article Tells Us That Is New

100 项与 CSL-111 相关的药物交易

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