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Natural killer cell lines in tumor immunotherapy

null

《医学前沿（英文）》 2012年第6卷第1期页码 56-66 doi: 10.1007/s11684-012-0177-7

摘要：

Natural killer (NK) cells are considered to be critical players in anticancer immunity. However, cancers are able to develop mechanisms to escape NK cell attack or to induce defective NK cells. Current NK cell-based cancer immunotherapy is aimed at overcoming NK cell paralysis through several potential approaches, including activating autologous NK cells, expanding allogeneic NK cells, usage of stable allogeneic NK cell lines and genetically modifying fresh NK cells or NK cell lines. The stable allogeneic NK cell line approach is more practical for quality-control and large-scale production. Additionally, genetically modifying NK cell lines by increasing their expression of cytokines and engineering chimeric tumor antigen receptors could improve their specificity and cytotoxicity. In this review, NK cells in tumor immunotherapy are discussed, and a list of therapeutic NK cell lines currently undergoing preclinical and clinical trials of several kinds of tumors are reviewed.

关键词： natural killer cell natural killer cell line tumor immunotherapy genetic modification

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Natural killer cells in liver diseases

null

《医学前沿（英文）》 2018年第12卷第3期页码 269-279 doi: 10.1007/s11684-018-0621-4

摘要：

The liver has been characterized as a frontline lymphoid organ with complex immunological features such as liver immunity and liver tolerance. Liver tolerance plays an important role in liver diseases including acute inflammation, chronic infection, autoimmune disease, and tumors. The liver contains a large proportion of natural killer (NK) cells, which exhibit heterogeneity in phenotypic and functional characteristics. NK cell activation, well known for its role in the immune surveillance against tumor and pathogen-infected cells, depends on the balance between numerous activating and inhibitory signals. In addition to the innate direct “killer” functions, NK cell activity contributes to regulate innate and adaptive immunity (helper or regulator). Under the setting of liver diseases, NK cells are of great importance for stimulating or inhibiting immune responses, leading to either immune activation or immune tolerance. Here, we focus on the relationship between NK cell biology, such as their phenotypic features and functional diversity, and liver diseases.

关键词： natural killer cell phenotype immune activation immune tolerance liver diseases

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Natural killer cells in hepatocellular carcinoma: current status and perspectives for future immunotherapeutic

null

《医学前沿（英文）》 2017年第11卷第4期页码 509-521 doi: 10.1007/s11684-017-0546-3

摘要：

Hepatocellular carcinoma (HCC) is currently the fifth most common malignancy and the third leading cause of cancer-related mortalities worldwide. In the last few years, treatments for HCC have significantly improved from a mere surgical resection to a series of minimally invasive therapies and targeted drugs. However, recurrence frequently occurs even upon curative therapeutics, and drug therapies generally produce disappointing results, with the overall prognosis dismal. This challenging clinical scenario warrants new effective and life-prolonging strategies for patients with HCC. Compelling evidence suggests that NK cells play a critical role in the immune function of the liver and in the immune defenses against HCC, indicating that HCC might be an ideal target for NK cell-based immunotherapies. To obtain comprehensive insights into the putative influence of NK cells on HCC, this paper summarizes current knowledge on NK cells in HCC and discusses the usefulness and prospects of NK cell-based immunotherapies. Critical issues that require consideration for the successful clinical translation of NK cell-based therapies are also addressed. If appropriately used and further optimized, NK cell-based therapies could dominate important roles in the future immunotherapeutic market of HCC.

关键词： natural killer cell hepatocellular carcinoma immunotherapy

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Astragaloside IV suppresses post-ischemic natural killer cell infiltration and activation in the brain

Baokai Dou, Shichun Li, Luyao Wei, Lixin Wang, Shiguo Zhu, Zhengtao Wang, Zunji Ke, Kaixian Chen, Zhifei Wang

《医学前沿（英文）》 2021年第15卷第1期页码 79-90 doi: 10.1007/s11684-020-0783-8

摘要： Natural killer (NK) cells, a type of cytotoxic lymphocytes, can infiltrate into ischemic brain and exacerbate neuronal cell death. Astragaloside IV (ASIV) is the major bioactive ingredient of , a Chinese herbal medicine, and possesses potent immunomodulatory and neuroprotective properties. This study investigated the effects of ASIV on post-ischemic brain infiltration and activation of NK cells. ASIV reduced brain infarction and alleviated functional deficits in MCAO rats, and these beneficial effects persisted for at least 7 days. Abundant NK cells infiltrated into the ischemic hemisphere on day 1 after brain ischemia, and this infiltration was suppressed by ASIV. Strikingly, ASIV reversed NK cell deficiency in the spleen and blood after brain ischemia. ASIV inhibited astrocyte-derived CCL2 upregulation and reduced CCR2 NK cell levels in the ischemic brain. Meanwhile, ASIV attenuated NK cell activating receptor NKG2D levels and reduced interferon-γ production. ASIV restored acetylation of histone H3 and the p65 subunit of nuclear factor-κB in the ischemic brain, suggesting inhibition of histone deacetylase (HDAC). Simultaneously, ASIV prevented p65 nuclear translocation. The effects of ASIV on reducing CCL2 production, restoring acetylated p65 levels and preventing p65 nuclear translocation were mimicked by valproate, an HDAC inhibitor, in astrocytes subjected to oxygen-glucose deprivation. Our findings suggest that ASIV inhibits post-ischemic NK cell brain infiltration and activation and reverses NK cell deficiency in the periphery, which together contribute to the beneficial effects of ASIV against brain ischemia. Furthermore, ASIV’s effects on suppressing NK cell brain infiltration and activation may involve HDAC inhibition.

关键词： astragaloside IV brain ischemia natural killer cells histone deacetylase nuclear factor-κB

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基于自然杀伤细胞的癌症免疫疗法的进展和前景 Review

胡渊, 田志刚, 张彩

《工程（英文）》 2019年第5卷第1期页码 106-114 doi: 10.1016/j.eng.2018.11.015

摘要：

自然杀伤（natural killer，NK）细胞是重要的先天免疫细胞，位于机体抵御病毒感染和癌症的第一道防线。临床试验正在应用各种类型的自然杀伤细胞治疗不同类型的肿瘤，包括自体或同种异体自然杀伤细胞、脐带血（umbilical cord blood，UCB）或诱导性多能干细胞（induced pluripotent stem cell

关键词：自然杀伤细胞免疫疗法癌症临床试验嵌合抗原受体

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Challenges of NK cell-based immunotherapy in the new era

null

《医学前沿（英文）》 2018年第12卷第4期页码 440-450 doi: tzg@ustc.edu.cn

摘要：

Natural killer cells (NKs) have a great potential for cancer immunotherapy because they can rapidly and directly kill transformed cells in the absence of antigen presensitization. Various cellular sources, including peripheral blood mononuclear cells (PBMCs), stem cells, and NK cell lines, have been used for producing NK cells. In particular, NK cells that expanded from allogeneic PBMCs exhibit better efficacy than those that did not. However, considering the safety, activities, and reliability of the cell products, researchers must develop an optimal protocol for producing NK cells from PBMCs in the manufacture setting and clinical therapeutic regimen. In this review, the challenges on NK cell-based therapeutic approaches and clinical outcomes are discussed.

关键词： natural killer cells immunotherapy adoptive transfer genetic modification immune checkpoint inhibitor

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Study of recombinant human IFN-α-2b bacilli Calmette–Guerin activated killer cells and against bladdercancer cell in vitro

FAN Xiaodong, HAN Ruifa

《医学前沿（英文）》 2007年第1卷第4期页码 377-380 doi: 10.1007/s11684-007-0073-8

摘要： Presently, one of the most potent immunotherapies is the application of bacillus Calmette Guerin (BCG) to prevent recurrences of the superficial bladder cancer. Despite its successful use, nonresponders and certain side effects remain a major obstacle. Therefore, current studies aim at developing recombinant BCG (rBCG) strains secreting Th1-like cytokines to improve the effectiveness of the therapy. In this study, a new type of rBCG strain constructed by Tianjin institute of Urology was tested for its immunostimulatory capacity . Peripheral blood monocytes (PBMC) were stimulated by recombinant BCG and transformed into bacilli Calmette–Guerin activated killer (BAK) cells, and the effect of anticancer BAK cells was studied. Recombinant IFN--2b-BCG, wild-type BCG (wBCG), wild-type BCG and IFN--2b were coincubated with PBMCs respectively , and the proliferation of PBMC was detected with MTT in different time. BAK cells have the ability to kill bladder tumor cells, and the antitumor activity of effecter cells was determined by LDH release assay. The result of MTT showed that the proliferation of PBMC in the recombinant BCG group was more powerful than in the other two groups (<0.05). The result of LDH release assay showed that the antitumor activity of BAK cells stimulated by Recombinant BCG was the highest in all groups. We conclude that the recombinant BCG can activate more PBMCs to anti-bladder cancer than wild-type BCG does.

关键词： Urology powerful 2b-BCG Tianjin institute wild-type

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NKT cells in liver diseases

null

《医学前沿（英文）》 2018年第12卷第3期页码 249-261 doi: 10.1007/s11684-018-0622-3

摘要：

Natural killer T cells are innate-like and tissue-resident lymphocytes, which recognize lipid antigens and are enriched in the liver. Natural killer T cells play important roles in infections, tumors, autoimmune diseases, and metabolic diseases. In this study, we summarize recent findings on biology of natural killer T cells and their roles in hepatitis B virus and hepatitis C virus infection, autoimmune liver diseases, alcoholic liver disease, nonalcoholic fatty liver disease, and hepatocellular carcinoma. Controversial results from previous studies are discussed, and indicate the dynamic alteration in the role of natural killer T cells during the progression of liver diseases, which might be caused by changes in natural killer T subsets, factors skewing cytokine responses, and intercellular crosstalk between natural killer T cells and CD1d-expressing cells or bystander cells.

关键词： natural killer T cells hepatitis B virus and hepatitis C virus infection autoimmune liver diseases alcoholic liver disease nonalcoholic fatty liver disease hepatocellular carcinoma

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Research on the theory and application of adsorbed natural gas used in new energy vehicles: A review

Zhengwei NIE,Yuyi LIN,Xiaoyi JIN

《机械工程前沿（英文）》 2016年第11卷第3期页码 258-274 doi: 10.1007/s11465-016-0381-2

摘要：

Natural gas, whose primary constituent is methane, has been considered a convincing alternative for the growth of the energy supply worldwide. Adsorbed natural gas (ANG), the most promising methane storage method, has been an active field of study in the past two decades. ANG constitutes a safe and low-cost way to store methane for natural gas vehicles at an acceptable energy density while working at substantially low pressures (3.5–4.0 MPa), allowing for conformable store tank. This work serves to review the state-of-the-art development reported in the scientific literature on adsorbents, adsorption theories, ANG conformable tanks, and related technologies on ANG vehicles. Patent literature has also been searched and discussed. The review aims at illustrating both achievements and problems of the ANG technologies-based vehicles, as well as forecasting the development trends and critical issues to be resolved of these technologies.

关键词： adsorbed natural gas (ANG) adsorbent adsorption theory conformable tank natural gas vehicles (NGVs)

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Effects of natural zeolite and sulfate ions on the mechanical properties and microstructure of plastic

《结构与土木工程前沿（英文）》 2022年第16卷第1期页码 86-98 doi: 10.1007/s11709-021-0793-x

摘要： One of the strategic materials used in earth-fill embankment dams and in modifying and preventing groundwater flow is plastic concrete (PlC). PlC is comprised of aggregates, water, cement, and bentonite. Natural zeolite (NZ) is a relatively abundant mineral resource and in this research, the microstructure, unconfined strength, triaxial behavior, and permeability of PlC made with 0%, 10%, 15%, 20%, and 25% replacement of cement by NZ were studied. Specimens of PIC-NZ were subjected to confined conditions and three different confining pressures of 200, 350, and 500 kPa were used to investigate their mechanical behavior and permeability. To study the effect of sulfate ions on the properties of PlC-NZ specimens, the specimens were cured in one of two different environments: normal condition and in the presence of sulfate ions. Results showed that increasing the zeolite content decreases the unconfined strength, elastic modulus, and peak strength of PlC-NZ specimens at the early ages of curing. However, at the later ages, increasing the zeolite content increases unconfined strength as well as the peak strength and elastic modulus. Specimens cured in the presence of sulfate ions indicated lower permeability, higher unconfined strength, elastic modulus, and peak strength due to having lower porosity.

关键词： plastic concrete sulfate resistance natural zeolite triaxial compression test SEM permeability

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A review on technologies with electricity generation potentials using liquified natural gas regasification

《能源前沿（英文）》 2023年第17卷第3期页码 332-379 doi: 10.1007/s11708-023-0863-y

摘要： In modern times, worldwide requirements to curb greenhouse gas emissions, and increment in energy demand due to the progress of humanity, have become a serious concern. In such scenarios, the effective and efficient utilization of the liquified natural gas (LNG) regasification cold energy (RCE), in the economically and environmentally viable methods, could present a great opportunity in tackling the core issues related to global warming across the world. In this paper, the technologies that are widely used to harness the LNG RCE for electrical power have been reviewed. The systems incorporating, the Rankine cycles, Stirling engines, Kalina cycles, Brayton cycles, Allam cycles, and fuel cells have been considered. Additionally, the economic and environmental studies apart from the thermal studies have also been reviewed. Moreover, the discussion regarding the systems with respect to the regassification pressure of the LNG has also been provided. The aim of this paper is to provide guidelines for the prospective researchers and policy makers in their decision making.

关键词： liquified natural gas cold energy power generation

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Accelerating the construction of natural gas system engineering in green smart cities

Xinhua MA

《工程管理前沿（英文）》 2019年第6卷第3期页码 453-456 doi: 10.1007/s42524-019-0046-z

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New nanostructured sorbents for desulfurization of natural gas

Lifeng WANG, Ralph T. YANG

《化学科学与工程前沿（英文）》 2014年第8卷第1期页码 8-19 doi: 10.1007/s11705-014-1411-4

摘要： Desulfurization of natural gas is achieved commercially by absorption with liquid amine solutions. Adsorption technology could potentially replace the solvent extraction process, particularly for the emerging shale gas wells with production rates that are generally lower than that from the large conventional reservoirs, if a superior adsorbent (sorbent) is developed. In this review, we focus our discussion on three types of sorbents: metal-oxide based sorbents, Cu/Ag-based and other commercial sorbents, and amine-grafted silicas. The advantages and disadvantages of each type are analyzed. Possible approaches for future developments to further improve these sorbents are suggested, particularly for the most promising amine-grafted silicas.

关键词： desulfurization natural gas desulfurization hydrogen sulfide sorbent amine-silica sorbent

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Dehydration of natural gas and biogas streams using solid desiccants: a review

Soheil Bahraminia, Mansoor Anbia, Esmat Koohsaryan

《化学科学与工程前沿（英文）》 2021年第15卷第5期页码 1050-1074 doi: 10.1007/s11705-020-2025-7

摘要： Natural gas and biogas are two mixtures that consist of methane as their main component. These two gas mixtures are usually saturated with water vapor, which cause many problems, such as damaging the gas processing equipment by increasing the gas’s corrosion potential or clogging the pipelines due to gas hydrate formation. Thus, removing water vapor from these gas streams is mandatory. In this review paper, the main dehydration methods have been overviewed, and scrutiny of the adsorption dehydration has been carried out. Furthermore, the most important solid desiccants and their improvements have been reviewed.

关键词： natural gas biogas dehydration adsorption solid desiccant