In normal tissue repair, macrophages exhibit a pro-inflammatory phenotype (M1) at early stages and a pro-healing phenotype (M2) at later stages. We have previously shown that M1 macrophages initiate angiogenesis while M2 macrophages promote vessel maturation. Therefore, we reasoned that scaffolds that promote sequential M1 and M2 polarization of infiltrating macrophages should result in enhanced angiogenesis and healing. To this end, we first analyzed the in vitro kinetics of macrophage phenotype switch using flow cytometry, gene expression, and cytokine secretion analysis. Then, we designed scaffolds for bone regeneration based on modifications of decellularized bone for a short release of interferon-gamma (IFNg) to promote the M1 phenotype, followed by a more sustained release of interleukin-4 (IL4) to promote the M2 phenotype. To achieve this sequential release profile, IFNg was physically adsorbed onto the scaffolds, while IL4 was attached via biotin-streptavidin binding. Interestingly, despite the strong interactions between biotin and streptavidin, release studies showed that biotinylated IL4 was released over 6 days. These scaffolds promoted sequential M1 and M2 polarization of primary human macrophages as measured by gene expression of ten M1 and M2 markers and secretion of four cytokines, although the overlapping phases of IFNg and IL4 release tempered polarization to some extent. Murine subcutaneous implantation model showed increased vascularization in scaffolds releasing IFNg compared to controls. This study demonstrates that scaffolds for tissue engineering can be designed to harness the angiogenic behavior of host macrophages towards scaffold vascularization. 相似文献
Myelofibrosis (MF) is a BCR-ABL1− myeloproliferative neoplasm that arises from hematopoietic stem and progenitor cells frequently harboring a somatic driver mutation in 1 of 3 genes: JAK2, CALR, or MPL. The pathologic features of this hematologic malignancy include myeloproliferation, diffuse bone marrow fibrosis, and overactivation of the JAK-STAT pathway, resulting in enhanced inflammatory cytokine release. The common clinical manifestations of MF include systemic symptoms, abnormal peripheral blood count levels, and splenomegaly. However, it has become increasingly appreciated that significant clinical heterogeneity exists among patients with MF. Two distinct MF clinical phenotypes include the myeloproliferative and myelodepletive phenotype, with peripheral blood counts being the main discerning feature. Patients with the myeloproliferative phenotype will present with elevated peripheral blood counts and often experience significant constitutional symptoms and progressive splenomegaly. In contrast, patients with the myelodepletive phenotype will have low peripheral blood counts and will frequently require transfusion support. Current frontline therapies for MF, include ruxolitinib and fedratinib, which can exacerbate cytopenias and thereby pose an impediment to effective treatment of the myelodepletive patient. The present review discusses the clinical and prognostic implications of the myelodepletive phenotype and the therapeutic options and limitations for this subset of patients, representing an unmet clinical need. 相似文献
Interleukin‐37 (IL‐37) is closely associated with several inflammatory diseases. However, the role of IL‐37 in the pathogenesis of rheumatoid arthritis (RA) remains unclear. The aim of this study was to assess the associations between serum levels of IL‐37 and disease activity, inflammatory cytokines, and bone loss in patients with RA. Serum cytokines levels were examined by Enzyme‐linked immunosorbent assay (ELISA). Radiographic bone erosion was assessed using the van der Heijde‐modified Sharp score and bone mineral density (BMD) was measured using DXA. Serum IL‐37 levels in RA patients were significantly higher than those in HCs (p<0.001), and were significantly positively correlated with clinical parameters of disease activity and serum levels of IL‐17 and IL‐23. In addition, serum IL‐37 levels were significantly higher in patients with stage IV of radiographic bone erosion than those with stage III and stage I–II, and they were significantly higher in those with osteopenia and osteoporosis than in those with normal BMD. Our results suggest that serum IL‐37 levels were increased in patients with RA and were positively associated with disease activity, IL‐17/IL‐23 and bone loss in RA, suggesting that IL‐37 may play a critical role in the pathogenesis of RA. 相似文献
目的探讨低分子肝素钙预防腰椎退行性疾病术后深静脉血栓形成(DVT)的有效性和安全性。方法回顾性分析广安市广安区人民医院68例腰椎退行性疾病患者的临床资料,术后均采用抗凝预防血栓形成,按照术后预防DVT所采用方式的不同分为对照组和低分子肝素钙组。分析比较2组患者术后引流量、切口愈合情况、DVT发生率、皮下瘀斑情况、血小板数值、凝血功能、D-二聚体。结果术后2组患者引流量、切口愈合情况、皮下瘀斑情况、凝血功能相关指标比较,差异无统计学意义(P>0.05)。术前和术后1、10 d 2组患者血小板数量的变化差异无统计学意义(P>0.05)。DVT发生率2组患者比较差异有统计学意义(P<0.05)。术前及术后1 d 2组患者D-二聚体比较,差异无统计学意义(P>0.05);术后10 d,对照组患者D-二聚体显著增加,2组比较差异有统计学意义(P<0.05)。结论腰椎退行性疾病术后使用低分子肝素钙进行抗凝,可以显著降低DVT的发生率,具有良好的安全性。 相似文献
Purpose: Non-ambulatory persons with cerebral palsy are prone to low bone mineral density. In ambulatory persons with cerebral palsy, bone mineral density deficits are expected to be small or absent, but a consensus conclusion is lacking. In this systematic review bone mineral density in ambulatory persons with cerebral palsy (Gross Motor Function Classification Scales I–III) was studied.
Materials and methods: Medline, Embase, and Web of Science were searched. According to international guidelines, low bone mineral density was defined as Z-score?≤??2.0. In addition, we focused on Z-score?≤??1.0 because this may indicate a tendency towards low bone mineral density.
Results: We included 16 studies, comprising 465 patients aged 1–65?years. Moderate and conflicting evidence for low bone mineral density (Z-score?≤??2.0) was found for several body parts (total proximal femur, total body, distal femur, lumbar spine) in children with Gross Motor Function Classification Scales II and III. We found no evidence for low bone mineral density in children with Gross Motor Function Classification Scale I or adults, although there was a tendency towards low bone mineral density (Z-score?≤??1.0) for several body parts.
Conclusions: Although more high-quality research is needed, results indicate that deficits in bone mineral density are not restricted to non-ambulatory people with cerebral palsy.
Implications for Rehabilitation
Although more high-quality research is needed, including adults and fracture risk assessment, the current study indicates that deficits in bone mineral density are not restricted to non-ambulatory people with CP.
Health care professionals should be aware that optimal nutrition, supplements on indication, and an active lifestyle, preferably with weight-bearing activities, are important in ambulatory people with CP, also from a bone quality point-of-view.
If indicated, medication and fall prevention training should be prescribed.
FGFR–TACC, found in different tumor types, is characterized by the fusion of a member of fibroblast grown factor receptor (FGFR) tyrosine kinase (TK) family to a member of the transforming acidic coiled-coil (TACC) proteins. Because chromosome numerical alterations, hallmarks of FGFR–TACC fusions are present in many hematological disorders and there are no data on the prevalence, we studied a series of patients with acute myeloid leukemia and myelodysplastic syndrome who presented numerical alterations using cytogenetic traditional analysis. None of the analyzed samples showed FGFR3–TACC3 gene fusion, so screening for this mutation at diagnosis is not recommended. 相似文献