RESUMO
Liver cancer, which is well-known to us as one of human most prevalent malignancies across the globe, poses a significant risk to live condition and life safety of individuals in every region of the planet. It has been shown that immune checkpoint treatment may enhance survival benefits and make a significant contribution to patient prognosis, which makes it a promising and popular therapeutic option for treating liver cancer at the current time. However, there are only a very few numbers of patients who can benefit from the treatment and there also exist adverse events such as toxic effects and so on, which is still required further research and discussion. Fortunately, the clustered regularly interspaced short palindromic repeat/CRISPR-associated nuclease 9 (CRISPR/Cas9) provides a potential strategy for immunotherapy and immune checkpoint therapy of liver cancer. In this review, we focus on elucidating the fundamentals of the recently developed CRISPR/Cas9 technology as well as the present-day landscape of immune checkpoint treatment which pertains to liver cancer. What's more, we aim to explore the molecular mechanism of immune checkpoint treatment in liver cancer based on CRISPR/Cas9 technology. At last, its encouraging and powerful potential in the future application of the clinic is discussed, along with the issues that already exist and the difficulties that must be overcome. To sum up, our ultimate goal is to create a fresh knowledge that we can utilize this new CRISPR/Cas9 technology for the current popular immune checkpoint therapy to overcome the treatment issues of liver cancer.
Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Edição de Genes/métodos , Imunoterapia/métodos , Inibidores de Checkpoint Imunológico/uso terapêutico , AnimaisRESUMO
Microstructural engineering on nickel-rich layered oxide (NRLO) cathode materials is considered a promising approach to increase both the capacity and lifespan of lithium-ion batteries by introducing high valence-state elements. However, rational regulation on NRLO microstructures based on a deep understanding of its capacity enhancement mechanism remains challenging. Herein for the first time, it is demonstrated that an increase of 14 mAh g-1 in reversible capacity at the first cycle can be achieved via tailoring the micro and nano structure of NRLO through introducing tungsten. Aberration-corrected scanning transmission electron microscopy (STEM) characterization reveals that the formation of a modified microstructure featured as coherent spinel twin boundaries. Theoretical modeling and electrochemical investigations further demonstrate that the capacity increase mechanism is related to such coherent spinel twin boundaries, which can lower the Li+ diffusion barrier and thus allow more Li+ to participate in deeper phase transitions. Meanwhile, the surface and grain boundaries of NRLOs are found to be modified by generating a dense and uniform LiWxOy phase, which further extends its cycle life by reducing side reactions with electrolytes. This work enables a comprehensive understanding of the capacity-increased mechanism and endows the remarkable potential of microstructural engineering for capacity- and lifespan-increased NRLOs.
RESUMO
The existing therapies for cancer are not remote satisfactory due to drug-resistance in tumors that are malignant. There is a pressing necessity to take a step forward to develop innovative therapies that can complement current ones. Multiple investigations have demonstrated that ferroptosis therapy, a non-apoptotic modality of programmed cell death, has tremendous potential in face of multiple crucial events, such as drug resistance and toxicity in aggressive malignancies. Recently, ferroptosis at the crosswalk of chemotherapy, materials science, immunotherapy, tumor microenvironment, and bionanotechnology has been presented to elucidate its therapeutic feasibility. Given the burgeoning progression of ferroptosis-based nanomedicine, the newest advancements in this field at the confluence of ferroptosis-inducers, nanotherapeutics, along with tumor microenvironment are given an overview. Here, the signaling pathways of ferroptosis-related were first talked about briefly. The emphasis discussion was placed on the pharmacological mechanisms and the nanodrugs design of ferroptosis inducing agents based on multiple distinct metabolism pathways. Additionally, a comprehensive overview of the action mechanisms by which the tumor microenvironment influences ferroptosis was elaborately descripted. Finally, some limitations of current researches and future research directions were also deliberately discussed to provide details about therapeutic avenues for ferroptosis-related diseases along with the design of anti-drugs.
Assuntos
Ferroptose , Neoplasias , Humanos , Microambiente Tumoral , Apoptose , Imunoterapia , Nanomedicina , Neoplasias/tratamento farmacológicoRESUMO
Both ursolic acid (UA) and sorafenib (Sora) have been generally utilized in cancer treatment, and the combination of the two has also shown a good anti-tumor effect. However, single-agent therapy for Hepatocellular carcinoma (HCC) has the disadvantages of multi-drug resistance, poor water solubility and low bioavailability, and the application of traditional nanocarrier materials is limited due to their low drug loading and low carrier-related toxicity. Therefore, we prepared US NPs with different proportions of UA and Sora by solvent exchange method for achieving synergistic HCC therapy. US NPs had suitable particle size, good dispersibility and storage stability, which synergistically inhibited the proliferation of HepG2 cells, SMMC7721 cells and H22 cells. In addition, we also proved that US NPs were able to suppress the migration of HepG2 cells and SMMC7721 cells and reduce the adhesion ability and colony formation ability of these cells. According to the results, US NPs could degrade the membrane potential of mitochondrial, participate in cell apoptosis, and synergistically induce autophagy. Collectively, the carrier-free US NPs provide new strategies for HCC treatment and new ideas for the development of novel nano-drug delivery systems containing UA and Sora.
Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Humanos , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Carcinoma Hepatocelular/patologia , Ácido Ursólico , Preparações Farmacêuticas , Neoplasias Hepáticas/patologia , Linhagem Celular TumoralRESUMO
In this work, industrial Kambara reactor desulphurization slag (KR slag) was indirectly carbonated. The effects of leaching time, leaching temperature, leaching agent types, and leaching agent concentration on the leaching ratio of calcium from KR slag were investigated. Subsequently, precipitated calcium carbonate (PCC) was synthesized by bubbling CO2 gas (flow rate of 15 mL/min) into 400 mL leaching solutions at 40 °C for 120 min with magnetic stirring at 300 rpm. It is found that calcium in KR slag can be selectively extracted using a diluted solution of ammonium acetate (CH3COONH4) or ammonium chloride (NH4Cl), while ammonium sulfate ((NH4)2SO4) solution is not suitable as leaching agent due to the formation of slightly soluble calcium sulfate (CaSO4). The leaching ratio of calcium is improved by extending the leaching time or increasing the leaching solvent concentration. However, leaching temperature has little effect on calcium extraction. After carbonating the NH4Cl- and CH3COONH4-leachate for 120 min, calcite and vaterite type PCC with a purity of 99% is synthesized. Each gram of KR slag can produce 0.794 g and 0.803 g PCC using NH4Cl and CH3COONH4 leaching agents respectively. Calculations show that 349.6 kg CO2 is captured by per ton of KR slag. The CO2 capture capacity of KR slag is significantly higher compared with previously studied materials.