基于网络药理学探索苏合香丸治疗新型冠状病毒肺炎的作用机制

目的：基于网络药理学探索苏合香丸治疗新型冠状病毒肺炎(COVID-19)的作用机制。方法：基于中药系统药理学分析平台(TCMSP)检索苏合香丸的活性成分,并以口服生物利用度(OB)≥30%及类药性(DL)≥0.18为标准筛选其主要活性成分,同时运用Genecards数据库筛选与COVID-19相关的基因。通过String数据库得到治疗靶点间相互作用关系,并构建靶蛋白相互作用网络图;利用Cytoscape软件构建苏合香丸中药-成分-作用靶点网络图。通过DAVID网络平台进行GO分析及KEGG信号通路分析。结果：通过筛选分析,筛选出苏合香丸中主要活性成分64个,潜在活性靶点基因64个,主要治疗靶点包括PTGS2、PTGS1、CALM1、F10、DPP4、PPARG、NOS3、PIK3CG、NOS2等。GO和KEGG富集分析结果主要涉及抗感染、炎症反应、免疫反应等生物学过程中的多条信号通路。结论：苏合香丸可是能通过调控多靶点多通路来防治新型冠状病毒肺炎,发挥抗病毒、抗炎、调节免疫等作用。     

基于网络药理学探索安宫牛黄丸中化学成分治疗新型冠状病毒肺炎的潜在机制

目的：本研究采用网络药理学的方法,探索安宫牛黄丸中化学成分防治新型冠状病毒肺炎(COVID-19)的潜在作用机制。方法：使用TCMSP数据库检索安宫牛黄丸中各中药组分的化学成分及其作用靶点,通过Genecards检索COVID-19的疾病作用靶点,将得到的两部分靶点取交集后导入Cytoscape构建“中药-化学成分-靶点”图,通过DAVID数据库进行GO和KEGG分析。结果：通过筛选分析,得出安宫牛黄丸主要化学成分44个,作用靶点基因62个,主要靶点包括PTGS2、PTGS1、NOS2、CALM1、DPP4、PIK3CG、NOS3、F10、PPARG、CDK2等。GO和KEGG富集分析共得到444个GO富集条目和117个KEGG富集条目,涉及病毒、细菌、寄生虫的感染、免疫、炎症反应等相关通路。结论：安宫牛黄丸可能通过调控多靶点、多通路,发挥抗病毒、抗炎、调节免疫等作用,从而起到防治COVID-19的作用。     

基于网络药理学的小儿肺热咳喘颗粒治疗肺炎的作用机制探讨

目的：利用网络药理学探究小儿肺热咳喘颗粒(XFKP)治疗肺炎的作用机制。方法：利用TCMSP、TCMID、Symmap数据库筛选XFKP中活性成分及其作用靶点,通过Genecards、Drugbank、Pharmgkb等数据库收集肺炎疾病靶点。提取成分与疾病靶点的交集靶点,借助STRING数据库绘制共同靶点相互作用网络,并以中位值筛选靶点。对所筛选靶点进行GO分析和KEGG信号通路富集分析。结果：共获得XFKP潜在活性成分239个和对应靶点269个,成分与疾病的共同靶点136个,以中位值筛选出核心靶点24个。以此靶点进行分析获取GO生物过程条目1782个,细胞组成条目45个,分子功能条目111个,KEGG通路139条。Cytoscape软件构建有效成分-靶点-疾病-信号通路网络图,以平均度值筛选核心成分10个,靶点23个。结论：XFKP可能通过关键有效成分槲皮素、木樨草素、柚皮素等,靶向核心靶点EGF、MMP9、PPARG等,从而调节IL-17、MAPK、TNF等信号通路作用于肺炎。     

防治新型冠状病毒肺炎纳米制剂的研究进展

虽然新型冠状病毒肺炎（Coronavirus Disease 2019,COVID-19）疫情已持续两年多,但全球发病率仍持续上升,研发预防和治疗COVID-19的制剂刻不容缓。纳米技术在开发用于COVID-19防治的药物制剂中起着不可估量的作用。本文介绍了纳米技术在制备COVID-19疫苗以及递送抗病毒药物中的应用,重点阐述了如何利用纳米载体的尺寸效应以及载体自身的免疫效应提高疫苗的安全性和有效性,并归纳总结了用于提高抗病毒药物的靶向递送效率以及改善药物作用效果的纳米递送载体,以期为新型防治COVID-19纳米制剂的研发提供参考。     

康复期血浆应用于急性病毒性传染病现状及其治疗新型冠状病毒肺炎前景

随着康复期血浆(convalescent plasma,CP)被成功地用于治疗多种急性病毒性传染病,其独到的治疗技术优势越来越受到肯定和认同。新近在中国武汉发现并鉴定一种命名为2019-nCoV(SARS-CoV-2)的新型冠状病毒,目前暂无特异性治疗其感染的有效手段。本文就CP应用于埃博拉、大流行流感、严重急性呼吸综合征(severe acute respiratory syndrome,SARS)、中东呼吸综合征(Middle East respiratory syndrome,MERS)的现状作一综述,并对其治疗新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)的前景作一展望。     

基于网络药理学和分子对接技术探讨清肝颗粒治疗慢性肝炎的作用机制

目的：利用网络药理学分子对接技术探讨清肝颗粒治疗慢性肝炎的作用机制。方法：首先利用TCMSP数据库收集清肝颗粒的中的化学成分以及靶点,利用OB、DL筛选候选活性化合物成分,然后通过CTD数据库、TTD数据库筛选出慢性肝炎相关的靶点;通过DAVID数据库对靶点进行GO富集分析和KEGG通路分析。运用Cytoscape3.6.1构建化合物-靶点、靶点-通路网络图;慢性肝炎通路整合与分析,最后通过AutoDock软件对主要活性成分及核心作用靶点进行分子对接验证。结果：检索得到清肝颗粒的化合物成分487个、靶点466个;筛选得到候选活性成分101个、慢性肝炎相关靶点115个,GO富集分析得到GOCC、GOMF、GOBP条目(p≤0.05)分别46、49、207个;KEGG通路富集筛选得到相关的通路23条,涉及钙信号通路、非酒精性脂肪肝、T细胞受体信号通路等。构建“慢性肝炎通路”,揭示了清肝颗粒在通路水平上协同发挥治疗慢性肝炎的效果,分子对接结果显示潜在的活性成分与核心靶点PTGS2、PPARG和NOS2均有较好的结合。结论：该研究通过运用网络药理学的研究方法发现清肝颗粒治疗慢性肝炎具有多成分、...     

新型冠状病毒肺炎康复者恢复期血浆中多重病原体检测方法的验证

目的 对新型冠状病毒肺炎(Coronavirus Disease 2019,COVID-19)康复者恢复期血浆中多重病原体检测方法进行系统性验证。方法 根据血浆样本实际情况,并结合试剂盒要求,分别对COVID-19康复者恢复期血浆中多重病原体分子生物学检测方法进行专属性、重复性、中间精密度及检测限验证,并对50份COVID-19康复者恢复期血浆样本进行方法适用性确认。结果 干扰试验和交叉试验结果均显示阳性样本和阴性样本检测均未受影响;同一检测人员或不同检测人员在不同时间相同检测条件下重复检测阳性对照4种病原体熔解温度(melting temperature,Tm)值的RSD分别为0.07%、0.14%、0.07%、0.14%和0.06%、0.23%、0.23%、0.20%,阴性对照内部质控(internal control,IC)和扩增质控(amplification quality control,AC)1和2 Tm值的RSD分别为0.07%、0.01%、0.07%、0.14%和0.11%、0.10%、0.15%、0.22%,重复性和中间精密度RSD均分别小于15%和20%,符合要求...     

新型冠状病毒预防性疫苗非临床研究评价的考虑

<正>随着新型冠状病毒(简称新冠)肺炎疫情在全球多点暴发快速蔓延,世界公共卫生安全面临严峻挑战,为应对来势汹汹的疫情,国内外疫苗研发企业迅速启动了新冠疫苗研发。目前在研的新冠疫苗类型多样,包括病毒灭活疫苗、基因工程重组疫苗、病毒载体类疫苗、核酸类疫苗(DNA疫苗和m RNA疫苗)等。从新冠疫情的致死率和导致感染者病情的严重程度,以及目前疫情控制手段和疾病转归情况,推动疫苗研发迫在眉睫。     

新型冠状病毒肺炎康复者恢复期血浆采集和质量特征

目的 探讨血液单采浆技术在新型冠状病毒肺炎(Coronavirus Disease 2019,COVID-19)康复者恢复期血浆采集工作中的应用及安全性,并分析COVID-19康复者恢复期血浆的质量特征.方法 捐献者知情后,登记捐献血浆者性别、年龄、出院或解除医学隔离日期等基本情况,体检后使用血液分离机单采浆技术采集C...     

新型冠状病毒疫苗的研发现状及展望

2019年12月发生的新型冠状病毒肺炎(Coronavirus disease 2019,COVID-19)对全球公共卫生造成巨大危机.世界卫生组织(World Health Organization,WHO)在2020年3月11日宣布COVID-19为全球大流行.目前,新型冠状病毒疫苗研发的技术路线主要有灭活疫苗、重...     

Non-Mouse Models of Atherosclerosis: Approaches to Exploring the Translational Potential of New Therapies

Cardiovascular disease is the largest single cause of disease-related mortality worldwide and the major underlying pathology is atherosclerosis. Atherosclerosis develops as a complex process of vascular lipid deposition and retention by modified proteoglycans, endothelial dysfunction and unresolved chronic inflammation. There are a multitude of current therapeutic agents, most based on lowering plasma lipid levels, but, overall, they have a lower than optimum level of efficacy and many deaths continue to arise from cardiovascular disease world-wide. To identify and evaluate potential novel cardiovascular drugs, suitable animal models that reproduce human atherosclerosis with a high degree of fidelity are required as essential pre-clinical research tools. Commonly used animal models of atherosclerosis include mice (ApoE^−/−, LDLR^−/− mice and others), rabbits (WHHL rabbits and others), rats, pigs, hamster, zebrafish and non-human primates. Models based on various wild-type and genetically modified mice have been extensively reviewed but mice may not always be appropriate. Thus, here, we provide an overview of the advantages and shortcomings of various non-mouse animal models of atherosclerotic plaque formation, and plaque rupture, as well as commonly used interventional strategies. Taken together, the combinatorial selection of suitable animal models readily facilitates reproducible and rigorous translational research in discovering and validating novel anti-atherosclerotic drugs.     

New Therapies for Dedifferentiated Papillary Thyroid Cancer

The number of thyroid cancers is increasing. Standard treatment usually includes primary surgery, thyroid-stimulating hormone suppressive therapy, and ablation of the thyroid remnant with radioactive iodine (RAI). Despite the generally good prognosis of thyroid carcinoma, about 5% of patients will develop metastatic disease, which fails to respond to RAI, exhibiting a more aggressive behavior. The lack of specific, effective and well-tolerated drugs, the scarcity of data about the association of multi-targeting drugs, and the limited role of radioiodine for dedifferentiated thyroid cancer, call for further efforts in the field of new drugs development. Rearranged during transfection (RET)/papillary thyroid carcinoma gene rearrangements, BRAF (B-RAF proto-oncogene, serine/threonine kinase) gene mutations, RAS (rat sarcoma) mutations, and vascular endothelial growth factor receptor 2 angiogenesis pathways are some of the known pathways playing a crucial role in the development of thyroid cancer. Targeted novel compounds have been demonstrated to induce clinical responses and stabilization of disease. Sorafenib has been approved for differentiated thyroid cancer refractory to RAI.     

New and Emerging Targeted Therapies for Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory skin disease deriving from the hair follicles. The formation of inflammatory nodules, abscesses, fistulas, and sinus tracts is characterized by a large inflow of key pro-inflammatory mediators, such as IFN-γ, TNF-α, IL-1, IL-17, and IL-12/23. Adalimumab is currently the only Food and Drug Administration (FDA)- and European Medicines Agency (EMA)-approved biologic therapy for moderate to severe HS in adults and adolescents. However, the long-term effectiveness of this TNF-α inhibitor in HS patients has shown to be highly variable. This review aims to review the evidence for emerging therapies that target the main pro-inflammatory cytokines in HS pathogenesis. A review of the literature was conducted, using the PubMed and Google Scholar repositories, as well as Clinicaltrials.gov. Presently, the most promising biologics in phase III trials are anti-IL-17 antibodies, secukinumab, and bimekizumab. Furthermore, an anti-IL-1 biologic, bermekimab, is currently in phase II trials, and shows encouraging results. Overall, the clinical efficacies of all new targeted therapies published up to this point are limited. More studies need to be performed to clarify the precise molecular pathology, and assess the efficacy of biological therapies for HS.     

A Proteomic Study Suggests Stress Granules as New Potential Actors in Radiation-Induced Bystander Effects

Besides the direct effects of radiations, indirect effects are observed within the surrounding non-irradiated area; irradiated cells relay stress signals in this close proximity, inducing the so-called radiation-induced bystander effect. These signals received by neighboring unirradiated cells induce specific responses similar with those of direct irradiated cells. To understand the cellular response of bystander cells, we performed a 2D gel-based proteomic study of the chondrocytes receiving the conditioned medium of low-dose irradiated chondrosarcoma cells. The conditioned medium was directly analyzed by mass spectrometry in order to identify candidate bystander factors involved in the signal transmission. The proteomic analysis of the bystander chondrocytes highlighted 20 proteins spots that were significantly modified at low dose, implicating several cellular mechanisms, such as oxidative stress responses, cellular motility, and exosomes pathways. In addition, the secretomic analysis revealed that the abundance of 40 proteins in the conditioned medium of 0.1 Gy irradiated chondrosarcoma cells was significantly modified, as compared with the conditioned medium of non-irradiated cells. A large cluster of proteins involved in stress granules and several proteins involved in the cellular response to DNA damage stimuli were increased in the 0.1 Gy condition. Several of these candidates and cellular mechanisms were confirmed by functional analysis, such as 8-oxodG quantification, western blot, and wound-healing migration tests. Taken together, these results shed new lights on the complexity of the radiation-induced bystander effects and the large variety of the cellular and molecular mechanisms involved, including the identification of a new potential actor, namely the stress granules.     

New and Emerging Targeted Therapies for Advanced Breast Cancer

In the United States, breast cancer is among the most frequently diagnosed cancers in women. Breast cancer is classified into four major subtypes: human epidermal growth factor receptor 2 (HER2), Luminal-A, Luminal-B, and Basal-like or triple-negative, based on histopathological criteria including the expression of hormone receptors (estrogen receptor and/or progesterone receptor) and/or HER2. Primary breast cancer treatments can include surgery, radiation therapy, systemic chemotherapy, endocrine therapy, and/or targeted therapy. Endocrine therapy has been shown to be effective in hormone receptor-positive breast cancers and is a common choice for adjuvant therapy. However, due to the aggressive nature of triple-negative breast cancer, targeted therapy is becoming a noteworthy area of research in the search for non-endocrine-targets in breast cancer. In addition to HER2-targeted therapy, other emerging therapies include immunotherapy and targeted therapy against critical checkpoints and/or pathways in cell growth. This review summarizes novel targeted breast cancer treatments and explores the possible implications of combination therapy.     

Regenerative Potential of Mesenchymal Stem Cells’ (MSCs) Secretome for Liver Fibrosis Therapies

Chronic liver injuries lead to liver fibrosis and then to end-stage liver cirrhosis. Liver transplantation is often needed as a course of treatment for patients in critical conditions, but limitations associated with transplantation prompted the continuous search for alternative therapeutic strategies. Cell therapy with stem cells has emerged as an attractive option in order to stimulate tissue regeneration and liver repair. Transplanted mesenchymal stem cells (MSCs) could trans-differentiate into hepatocyte-like cells and, moreover, show anti-fibrotic and immunomodulatory effects. However, cell transplantation may lead to some uncontrolled side effects, risks associated with tumorigenesis, and cell rejection. MSCs’ secretome includes a large number of soluble factors and extracellular vesicles (EVs), through which they exert their therapeutic role. This could represent a cell-free strategy, which is safer and more effective than MSC transplantation. In this review, we focus on cell therapies based on MSCs and how the MSCs’ secretome impacts the mechanisms associated with liver diseases. Moreover, we discuss the important therapeutic role of EVs and how their properties could be further used in liver regeneration.     

New Perspectives to Improve Mesenchymal Stem Cell Therapies for Drug-Induced Liver Injury

Drug-induced liver injury (DILI) is one of the leading causes of acute liver injury. Many factors may contribute to the susceptibility of patients to this condition, making DILI a global medical problem that has an impact on public health and the pharmaceutical industry. The use of mesenchymal stem cells (MSCs) has been at the forefront of regenerative medicine therapies for many years, including MSCs for the treatment of liver diseases. However, there is currently a huge gap between these experimental approaches and their application in clinical practice. In this concise review, we focus on the pathophysiology of DILI and highlight new experimental approaches conceived to improve cell-based therapy by the in vitro preconditioning of MSCs and/or the use of cell-free products as treatment for this liver condition. Finally, we discuss the advantages of new approaches, but also the current challenges that must be addressed in order to develop safer and more effective procedures that will allow cell-based therapies to reach clinical practice, enhancing the quality of life and prolonging the survival time of patients with DILI.     

Antibacterial and Cytotoxicity Evaluation of New Hydroxyapatite-Based Granules Containing Silver or Gallium Ions with Potential Use as Bone Substitutes

The aim of the current work was to study the physicochemical properties and biological activity of different types of porous granules containing silver or gallium ions. Firstly, hydroxyapatites powders doped with Ga³⁺ or Ag⁺ were synthesized by the standard wet method. Then, the obtained powders were used to fabricate ceramic microgranules (AgM and GaM) and alginate/hydroxyapatite composite granules (AgT and GaT). The ceramic microgranules were also used to prepare a third type of granules (AgMT and GaMT) containing silver or gallium, respectively. All the granules turned out to be porous, except that the AgT and GaT granules were characterized by higher porosity and a better developed specific surface, whereas the microgranules had very fine, numerous micropores. The granules revealed a slow release of the substituted ions. All the granules except AgT were classified as non-cytotoxic according to the neutral red uptake (NRU) test and the MTT assay. The obtained powders and granules were subjected to various antibacterial test towards the following four different bacterial strains: Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Escherichia coli. The Ag-containing materials revealed high antibacterial activity.