Metal-organic framework IRMOFs coated with a temperaturesensitive gel delivering norcantharidin to treat liver cancer

BACKGROUND Norcantharidin(NCTD)is suitable for the treatment of primary liver cancer,especially early and middle primary liver cancer.This compound can reduce tumors and improve immune function.However,the side effects of NCTD have limited its application.There is a marked need to reduce the side effects and increase the efficacy of NCTD.AIM To develop a nanomaterial carrier,NCTD-loaded metal-organic framework IRMOF-3 coated with a temperature-sensitive gel(NCTD-IRMOF-3-Gel),aiming to improve the anticancer activity of NCTD and reduce the drug dose.METHODS NCTD-IRMOF-3-Gel was obtained by a coordination reaction.The apparent characteristics and in vitro release of NCTD-IRMOF-3-Gel were investigated.Cell cytotoxicity assays,flow cytometry,and apoptosis experiments in mouse hepatoma(Hepa1-6)cells were used to determine the anti-liver cancer activity of NCTD-IRMOF-3-Gel in in vitro models.RESULTS The particle size of NCTD-IRMOF-3-Gel was 50-100 nm,and the particle size distribution was uniform.The release curve showed that NCTD-IRMOF-3-Gel had an obvious sustained-release effect.The cytotoxicity assays showed that the free drug NCTD and NCTD-IRMOF-3-Gel treatments markedly inhibited Hepa1-6 cell proliferation,and the inhibition rate increased with increasing drug concentration.By flow cytometry,NCTD-IRMOF-3-Gel was observed to block the Hepa1-6 cell cycle in the S and G2/M phases,and the thermosensitive gel nanoparticles may inhibit cell proliferation by inducing cell cycle arrest.Apoptosis experiments showed that NCTD-IRMOF-3-Gel induced the apoptosis of Hepa1-6 cells.CONCLUSION Our results indicated that the NCTD-IRMOF-3-Gel may be beneficial for liver cancer disease treatment.

Anti-inflammatory effect and antihepatoma mechanism of carrimycin

BACKGROUND New drugs are urgently needed for the treatment of liver cancer, a feat that could be feasibly accomplished by finding new therapeutic purposes for marketed drugs to save time and costs. As a new class of national anti-infective drugs, carrimycin(CAM) has strong activity against gram-positive bacteria and no cross resistance with similar drugs. Studies have shown that the components of CAM have anticancer effects.AIM To obtain a deeper understanding of CAM, its distribution, metabolism and antiinflammatory effects were assessed in the organs of mice, and its mechanism of action against liver cancer was predicted by a network pharmacology method.METHODS In this paper, the content of isovaleryl spiramycin Ⅲ was used as an index to assess the distribution and metabolism of CAM and its effect on inflammatory factors in various mouse tissues and organs. Reverse molecular docking technology was utilized to determine the target of CAM, identify each target protein based on disease type, and establish a target protein-disease type network to ascertain the effect of CAM in liver cancer. Then, the key action targets of CAM in liver cancer were screened by a network pharmacology method, and the core targets were verified by molecular docking and visual analyses.RESULTS The maximum CAM concentration was reached in the liver, kidney, lung and spleen 2.5 h after intragastric administration. In the intestine, the maximum drug concentration was reached 0.5 h after administration. In addition, CAM significantly reduced the interleukin-4(IL-4) levels in the lung and kidney and especially the liver and spleen;moreover, CAM significantly reduced the IL-1β levels in the spleen, liver, and kidney and particularly the small intestine and lung. CAM is predicted to regulate related pathways by acting on many targets,such as albumin, estrogen receptor 1, epidermal growth factor receptor and caspase 3, to treat cancer, inflammation and other diseases.CONCLUSION We determined that CAM inhibited inflammation. We also predicted the complex multitargeted effects of CAM that involve multiple pathways and the diversity of these effects in the treatment of liver cancer, which provides a basis and direction for further clinical research.

梯度纳米结构Inconel 625合金的形成机理及磨损行为

采用SEM、TEM和球盘式滑动磨损机研究梯度纳米结构(GNS) Inconel 625合金的形成机理和磨损行为。结果表明,表面机械研磨处理(SMGT)诱导产生深度约为800μm的梯度结构,其由表层纳米晶层、纳米层片层、纳米孪晶层和严重变形层组成,对应的显微硬度由6.95 GPa (最表层)梯度降低到2.77 GPa (粗晶基体)。同时,高密度纳米孪晶的形成以及随后的纳米孪晶与位错之间的交互作用导致纳米晶层的形成。经SMGT处理样品的磨痕宽度和深度、磨损量和磨损率均小于未处理粗晶样品的;此外,两种样品的磨损机制主要是磨料磨损和粘着磨损,并伴有轻微的氧化磨损。GNS Inconel 625合金耐磨性的显著增强归因于GNS表层具有高显微硬度、高残余压应力和高应变能力。

In vivo evaluation and mechanism prediction of anti-diabetic foot ulcer based on component analysis of Ruyi Jinhuang powder

BACKGROUND Diabetes is a metabolic disease with a high complication rate.Diabetic foot ulcers(DFUs)seriously affect the quality of life of patients.A total of 15%-20%of diabetic patients develop DFUs,which heal with difficulty over a long time and can result in amputation and disability.Traditional Chinese medicine has a unique effect in the treatment of skin ulcerative diseases.Ruyi Jinhuang powder(RHP)is one of the classic prescriptions in traditional Chinese medicine and is widely used in clinical practice.AIM To verify the ability of RHP to promote wound healing by electron microscopy analysis in animal models and hematoxylin-eosin(HE)staining.The effective components of RHP were extracted and identified by gas chromatography-mass spectrometry(GC-MS),and the obtained chemical components were analyzed by network pharmacology methods to predict its therapeutic mechanism.METHODS Sprague Dawley rats were injected with streptozotocin to establish the DFU model.HE staining was used to observe the wound tissue under an electron microscope.The chemical constituents of RHP were extracted first by supercritical fluid extraction and alcohol extraction,and then,GC-MS and ultra-performance liquid chromatography–MS were used to separately identify the chemical constituents.In addition,the"herb-component-target"link was established through the Traditional Chinese Medicine Systems Pharmacology database to obtain the target information,and the molecular docking of important components and key targets was performed in Discovery Studio software.Cytoscape software was used to visualize and analyze the relationship between the chemical composition,targets and Traditional Chinese Medicine network.RESULTS RHP promoted DFU healing in rats by affecting fibroblasts and nerve cells.A total of 89 chemical components were obtained by GC-MS.Network pharmacological analysis revealed that RHP was associated with 36 targets and 27 pathways in the treatment of DFU,of which the important components were luteolin,trans caryophyllene,ar-turmerone,palmitic acid,methyl palmitate,gallic acid,demethoxycurcumin,berberine,and rheic acid.The key targets were posttranscriptional silencing,topoisomerase II alpha,muscarinic acetylcholine receptor M2,interleukin 6,tumor necrosis factor and retinoic X receptor alpha,and the key pathways were the phosphoinositide 3-kinase-protein kinase B signaling pathway,neuroactive ligand–receptor interactions,and the forkhead box O signaling pathway.CONCLUSION Our results indicated that RHP may play a role in the treatment of DFU through these target pathways by affecting insulin resistance,altering the nervous system and immune system,participating in inflammatory responses and regulating cell proliferation,differentiation and apoptosis through other specific mechanisms.