Neddylation suppression by a macrophage membrane-coated nanoparticle promotes dual immunomodulatory repair of diabetic wounds

Oxidative stress,infection,and vasculopathy caused by hyperglycemia are the main barriers for the rapid repair of foot ulcers in patients with diabetes mellitus(DM).In recent times,the discovery of neddylation,a new type of post-translational modification,has been found to regulate various crucial biological processes including cell metabolism and the cell cycle.Nevertheless,its capacity to control the healing of wounds in diabetic patients remains unknown.This study shows that MLN49224,a compound that inhibits neddylation at low concentrations,enhances the healing of diabetic wounds by inhibiting the polarization of M1 macrophages and reducing the secretion of inflammatory factors.Moreover,it concurrently stimulates the growth,movement,and formation of blood vessel endothelial cells,leading to expedited healing of wounds in individuals with diabetes.The drug is loaded into biomimetic macrophage-membrane-coated PLGA nanoparticles(M-NPs/MLN4924).The membrane of macrophages shields nanoparticles from being eliminated in the reticuloendothelial system and counteracts the proinflammatory cytokines to alleviate inflammation in the surrounding area.The extended discharge of MLN4924 from M-NPs/MLN4924 stimulates the growth of endothelial cells and the formation of tubes,along with the polarization of macrophages towards the anti-inflammatory M2 phenotype.By loading M-NPs/MLN4924 into a hydrogel,the final formulation is able to meaningfully repair a diabetic wound,suggesting that M-NPs/MLN4924 is a promising engineered nanoplatform for tissue engineering.

具有线性介电常数Ogden型锥形介电弹性体作动器的力电响应研究

为研究锥形介电弹性体作动器在非理想状态下的力电特性,本文采用多材料常数Ogden模型,考虑无预拉伸和预拉伸的情况下,通过引入依赖拉伸率的线性介电常数,得到非理想状态下的本构关系.对薄膜受到外力外电压作用时发生面外非线性轴对称大变形进行数值模拟.结果表明在预拉伸下,随着电致伸缩系数的减小,薄膜变形,拉伸量呈稳定状态,真实电场分布呈均匀状态,研究结果有利于理解介电弹性体的力电稳定性,更好地指导此类作动器的设计.

MicroRNAs as potential therapeutic targets for pancreatic cancer

Pancreatic cancer is one of the most aggressive malignancies. The poor prognosis of pancreatic cancer patients is mainly attributed to low diagnostic rate at the early stage, highly aggressive nature coupled with the inadequate efficacy of current chemotherapeutic regimens. Novel therapeutic strategies are urgently needed for pancreatic cancer. MicroRNAs (miRNAs) play an important regulatory role in key processes of cancer development. The aberrant expression of miRNAs is often involved in the initiation, progression, and metastasis of pancreatic cancer. The discovery of tumor suppressor miRNAs provides prospects for the development of a novel treatment strategy for pancreatic cancer. We reviewed recent progress on the understanding of the role of miRNAs in pancreatic cancer, highlighted the efficient application of miRNAs-based therapies for pancreatic cancer in animal models and clinical trials, and proposed future prospects. This review focuses on the promise of integrating miRNAs into the treatment of pancreatic cancer and provides guidance for the development of precision medicine for pancreatic cancer.

Immunomodulatory Nanosystems:Advanced Delivery Tools for Treating Chronic Wounds

The increasingly aging society led to a rise in the prevalence of chronic wounds(CWs),posing a significant burden to public health on a global scale.One of the key features of CWs is the presence of a maladjusted immune microenvironment characterized by persistent and excessive(hyper)inflammation.A variety of immunomodulatory therapies have been proposed to address this condition.Yet,to date,current delivery systems for immunomodulatory therapy remain inadequate and lack efficiency.This highlights the need for new therapeutic delivery systems,such as nanosystems,to manage the pathological inflammatory imbalance and,ultimately,improve the treatment outcomes of CWs.While a plethora of immunomodulatory nanosystems modifying the immune microenvironment of CWs have shown promising therapeutic effects,the literature on the intersection of immunomodulatory nanosystems and CWs remains relatively scarce.Therefore,this review aims to provide a comprehensive overview of the pathogenesis and characteristics of the immune microenvironment in CWs,discuss important advancements in our understanding of CW healing,and delineate the versatility and applicability of immunomodulatory nanosystems-based therapies in the therapeutic management of CWs.In addition,we herein also shed light on the main challenges and future perspectives in this rapidly evolving research field.

Recombinant adeno-associated virus-based gene therapy combined with tissue engineering for musculoskeletal regenerative medicine

Recombinant adeno-associated viral(rAAV)vector-mediated gene delivery is a novel molecular therapeutic approach for musculoskeletal disorders which achieves tissue regeneration by delivering a transgene to the impaired tissue.In recent years,substantial scientific progress in rAAV gene therapy has led to several clinical trials for human musculoskeletal diseases.Nevertheless,there are still limitations in developing an optimal gene therapy model due to the low transduction efficiency and fast degradation of the gene vectors.To overcome the challenges of rAAV gene therapy,tissue engineering combined with gene therapy has emerged as a more promising alternative.An rAAV viral vector incorporated into a biomaterial has a more controlled gene expression,lower immune response,and higher efficiency.A number of biomaterials and architectures have been combined with rAAV viral vectors,each having its own advantages and limitations.This review aims to give a broad introduction to combinatorial therapy and the recent progress this new technology has offered.