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Non-genetic mechanisms of diabetic nephropathy

null

《医学前沿(英文)》 2017年 第11卷 第3期   页码 319-332 doi: 10.1007/s11684-017-0569-9

摘要:

Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetes mellitus patients and is characterized by thickened glomerular basement membrane, increased extracellular matrix formation, and podocyte loss. These phenomena lead to proteinuria and altered glomerular filtration rate, that is, the rate initially increases but progressively decreases. DN has become the leading cause of end-stage renal disease. Its prevalence shows a rapid growth trend and causes heavy social and economic burden in many countries. However, this disease is multifactorial, and its mechanism is poorly understood due to the complex pathogenesis of DN. In this review, we highlight the new molecular insights about the pathogenesis of DN from the aspects of immune inflammation response, epithelial–mesenchymal transition, apoptosis and mitochondrial damage, epigenetics, and podocyte–endothelial communication. This work offers groundwork for understanding the initiation and progression of DN, as well as provides ideas for developing new prevention and treatment measures.

关键词: diabetic nephropathy     immune inflammatory response     epithelial–mesenchymal transition     apoptosis     mitochondrial damage     epigenetics     podocyte–endothelial communication    

Persistence of humoral and cellular immune response after SARS-CoV-2 infection: opportunities and challenges

Tangchun Wu

《医学前沿(英文)》 2020年 第14卷 第6期   页码 816-819 doi: 10.1007/s11684-020-0823-4

Liver-directed treatment is associated with improved survival and increased response to immune checkpoint

《医学前沿(英文)》   页码 878-888 doi: 10.1007/s11684-023-0993-y

摘要: Metastases of uveal melanoma (UM) spread predominantly to the liver. Due to low response rates to systemic therapies, liver-directed therapies (LDT) are commonly used for tumor control. The impact of LDT on the response to systemic treatment is unknown. A total of 182 patients with metastatic UM treated with immune checkpoint blockade (ICB) were included in this analysis. Patients were recruited from prospective skin cancer centers and the German national skin cancer registry (ADOReg) of the German Dermatologic Cooperative Oncology Group (DeCOG). Two cohorts were compared: patients with LDT (cohort A, n = 78) versus those without LDT (cohort B, n = 104). Data were analyzed for response to treatment, progression-free survival (PFS), and overall survival (OS). The median OS was significantly longer in cohort A than in cohort B (20.1 vs. 13.8 months; P = 0.0016) and a trend towards improved PFS was observed for cohort A (3.0 vs. 2.5 months; P = 0.054). The objective response rate to any ICB (16.7% vs. 3.8%, P = 0.0073) and combined ICB (14.1% vs. 4.5%, P = 0.017) was more favorable in cohort A. Our data suggest that the combination of LDT with ICB may be associated with a survival benefit and higher treatment response to ICB in patients with metastatic UM.

关键词: uveal melanoma     liver-directed therapy     immune checkpoint blockade     SIRT     anti-PD-1     anti-CTLA-4    

Hyperthermia on skin immune system and its application in the treatment of human papillomavirus-infected

null

《医学前沿(英文)》 2014年 第8卷 第1期   页码 1-5 doi: 10.1007/s11684-014-0309-3

摘要:

Hyperthermia is a condition characterized by increased body temperature as a consequence of failed thermoregulation. Hyperthermia occurs when a body produces or absorbs more heat than it dissipates. Hyperthermia also elicits various effects on the physiology of living cells. For instance, fever-range temperature (39β°C to 40β°C) can modulate the activities of immune cells, including antigen-presenting cells, T cells, and natural killer cells. Heat shock temperature (41β°C to 43β°C) can increase the immunogenicity of tumor cells. Cytotoxic temperature (>43β°C) can create an antigen source to induce an anti-tumor immune response. The immunomodulatory effect of hyperthermia has promoted an interest in hyperthermia-aided immunotherapy, particularly against tumors. Hyperthermia has also been used to treat deep fungal, bacterial, and viral skin infections. We conducted a series of open or controlled trials to treat skin human papillomavirus infection by inducing local hyperthermia. More than half of the patients were significantly cured compared with those in the control trial. A series of challenging clinical cases, such as large lesions in pregnant patients or patients with diabetes mellitus, were also successfully and safely managed using the proposed method. However, further studies should be conducted to clarify the underlying mechanisms and promote the clinical applications of hyperthermia.

关键词: hyperthermia     HPV     immune response     virus     tumor    

Immune response triggered by the ablation of hepatocellular carcinoma with nanosecond pulsed electric

Jianpeng Liu, Xinhua Chen, Shusen Zheng

《医学前沿(英文)》 2021年 第15卷 第2期   页码 170-177 doi: 10.1007/s11684-020-0747-z

摘要: Nanosecond pulsed electric field (nsPEF) is a novel, nonthermal, and minimally invasive modality that can ablate solid tumors by inducing apoptosis. Recent animal experiments show that nsPEF can induce the immunogenic cell death of hepatocellular carcinoma (HCC) and stimulate the host’s immune response to kill residual tumor cells and decrease distant metastatic tumors. nsPEF-induced immunity is of great clinical importance because the nonthermal ablation may enhance the immune memory, which can prevent HCC recurrence and metastasis. This review summarized the most advanced research on the effect of nsPEF. The possible mechanisms of how locoregional nsPEF ablation enhances the systemic anticancer immune responses were illustrated. nsPEF stimulates the host immune system to boost stimulation and prevail suppression. Also, nsPEF increases the dendritic cell loading and inhibits the regulatory responses, thereby improving immune stimulation and limiting immunosuppression in HCC-bearing hosts. Therefore, nsPEF has excellent potential for HCC treatment.

关键词: nanosecond pulsed electric fields (nsPEF)     hepatocellular carcinoma (HCC)     immune response     recurrence     metastasis    

Integrated analysis of gut microbiome and host immune responses in COVID-19

《医学前沿(英文)》 2022年 第16卷 第2期   页码 263-275 doi: 10.1007/s11684-022-0921-6

摘要: Emerging evidence indicates that the gut microbiome contributes to the host immune response to infectious diseases. Here, to explore the role of the gut microbiome in the host immune responses in COVID-19, we conducted shotgun metagenomic sequencing and immune profiling of 14 severe/critical and 24 mild/moderate COVID-19 cases as well as 31 healthy control samples. We found that the diversity of the gut microbiome was reduced in severe/critical COVID-19 cases compared to mild/moderate ones. We identified the abundance of some gut microbes altered post-SARS-CoV-2 infection and related to disease severity, such as Enterococcus faecium, Coprococcus comes, Roseburia intestinalis, Akkermansia muciniphila, Bacteroides cellulosilyticus and Blautia obeum. We further analyzed the correlation between the abundance of gut microbes and host responses, and obtained a correlation map between clinical features of COVID-19 and 16 severity-related gut microbe, including Coprococcus comes that was positively correlated with CD3+/CD4+/CD8+ lymphocyte counts. In addition, an integrative analysis of gut microbiome and the transcriptome of peripheral blood mononuclear cells (PBMCs) showed that genes related to viral transcription and apoptosis were up-regulated in Coprococcus comes low samples. Moreover, a number of metabolic pathways in gut microbes were also found to be differentially enriched in severe/critical or mild/moderate COVID-19 cases, including the superpathways of polyamine biosynthesis II and sulfur oxidation that were suppressed in severe/critical COVID-19. Together, our study highlighted a potential regulatory role of severity related gut microbes in the immune response of host.

关键词: COVID-19     SARS-COV-2     gut microbiome     immune response    

Universal influenza virus vaccines: what can we learn from the human immune response following exposure

null

《医学前沿(英文)》 2017年 第11卷 第4期   页码 471-479 doi: 10.1007/s11684-017-0602-z

摘要:

Several universal influenza virus vaccine candidates based on eliciting antibodies against the hemagglutinin stalk domain are in development. Typically, these vaccines induce responses that target group 1 or group 2 hemagglutinins with little to no cross-group reactivity and protection. Similarly, the majority of human anti-stalk monoclonal antibodies that have been isolated are directed against group 1 or group 2 hemagglutinins with very few that bind to hemagglutinins of both groups. Here we review what is known about the human humoral immune response to vaccination and infection with H7 subtype influenza viruses on a polyclonal and monoclonal level. It seems that unlike vaccination with H5 hemagglutinin, which induces antibody responses mostly restricted to the group 1 stalk domain, H7 exposure induces both group 2 and cross-group antibody responses. A better understanding of this phenomenon and the underlying mechanisms might help to develop future universal influenza virus vaccine candidates.

关键词: universal influenza virus vaccine     hemagglutinin stalk     H7N9    

Metformin and metabolic diseases: a focus on hepatic aspects

null

《医学前沿(英文)》 2015年 第9卷 第2期   页码 173-186 doi: 10.1007/s11684-015-0384-0

摘要:

Metformin has been widely used as a first-line anti-diabetic medicine for the treatment of type 2 diabetes (T2D). As a drug that primarily targets the liver, metformin suppresses hepatic glucose production (HGP), serving as the main mechanism by which metformin improves hyperglycemia of T2D. Biochemically, metformin suppresses gluconeogenesis and stimulates glycolysis. Metformin also inhibits glycogenolysis, which is a pathway that critically contributes to elevated HGP. While generating beneficial effects on hyperglycemia, metformin also improves insulin resistance and corrects dyslipidemia in patients with T2D. These beneficial effects of metformin implicate a role for metformin in managing non-alcoholic fatty liver disease. As supported by the results from both human and animal studies, metformin improves hepatic steatosis and suppresses liver inflammation. Mechanistically, the beneficial effects of metformin on hepatic aspects are mediated through both adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent pathways. In addition, metformin is generally safe and may also benefit patients with other chronic liver diseases.

关键词: metformin     diabetes     hepatic steatosis     inflammatory response     insulin resistance    

Heterologous expression of signal protein 14-3-3 in and the subsequent immune response in mice

ZHENG Meijuan, SHEN Jilong, LUO Qingli, XU Yuanhong

《医学前沿(英文)》 2008年 第2卷 第1期   页码 95-99 doi: 10.1007/s11684-008-0017-y

摘要: Schistosomiasis japonica, a zoonosis caused by , is endemic to the Philippines and China. Several vaccine candidates have been identified and tested in different animal models, but it is still unclear which will be optimal for testing in the field. Therefore, new antigens and strategies are necessary for vaccine development against schistosomiasis japonica. The Sj14-3-3 gene was amplified and subcloned into the expression vector pPICZ?-B and transformed into X-33 by electroporation. Three transformants were induced with methanol. The cultural supernatant was collected and tested by SDS-PAGE and Western blotting. The protein of rSj14-3-3 was prepared and purified and BALB/c mice were immunized which was followed by a challenging infection. The immuno-protection was then evaluated. The Sj14-3-3 gene was expressed and secreted into the medium and its molecular weight was about 35000 as determined by SDS-PAGE. Western blotting showed that the protein had a high specificity against mouse-anti-Sj14-3-3 monoclonal antibody and rSj14-3-3 had a promising immune reactivity. The results of the immuno-protective experiments revealed that the worm reduction was 26.0%, 32.2%, and 36.8%, respectively. The number of eggs in liver tissue was reduced by 36.8%, 43.2%, and 46.1%, respectively. The recombinant Sj14-3-3 of eukaryotic expression in was successfully harvested. The molecular vaccine of Sj14-3-3 could partially induce resistance to the infection with in BALB/c mice. The recombinant protein Sj14-3-3 has promising immunological potentials for further approach to the diagnosis and development of molecular vaccine.

关键词: development     challenging     rSj14-3-3     resistance     cultural supernatant    

Construction and humoral immune response of Epstein-Barr virus latent membrane protein 2 DNA vaccine

Jianqing PAN PhD, Qin ZHANG MD, Daowen WANG MD, PhD,

《医学前沿(英文)》 2009年 第3卷 第4期   页码 390-395 doi: 10.1007/s11684-009-0087-5

摘要: We constructed a eukaryotic expression plasmid encoding Epstein-Barr virus latent membrane protein 2 (EBV, LMP2) and evaluated its effects on humoral immunity. First, the encoding sequence of the EBV was amplified from B95−8 cell RNA by reverse transcription polymerase chain reaction (RT-PCR) and then was directionally cloned into eukaryotic expression vector pcDNA3.1. It was employed to evaluate immune response of the mice inoculated doubly with the DNA vaccine. The serum antibody against LMP2 was detected with enzyme-linked immunosorbent assay (ELISA). The recombinant plasmid pcDNA3.1- was confirmed by the restrictive endonuclease analysis and sequence analysis. The serum titer of IgG antibody against LMP2 epitope in the mice immunized with the DNA vaccine encoding LMP2 was up to 1∶4000. In conclusion, the EBV DNA vaccine can induce a strong humoral immune response in mice.

关键词: Epstein-Barr virus     latent membrane protein 2     nasopharyngeal carcinoma     humoral immunity    

Programming CAR T cells to enhance anti-tumor efficacy through remodeling of the immune system

Xiaohui Wang, Zhiqiang Wu, Wei Qiu, Ping Chen, Xiang Xu, Weidong Han

《医学前沿(英文)》 2020年 第14卷 第6期   页码 726-745 doi: 10.1007/s11684-020-0746-0

摘要: Chimeric antigen receptor (CAR) T cells have been indicated effective in treating B cell acute lymphoblastic leukemia and non-Hodgkin lymphoma and have shown encouraging results in preclinical and clinical studies. However, CAR T cells have achieved minimal success against solid malignancies because of the additional obstacles of their insufficient migration into tumors and poor amplification and persistence, in addition to antigen-negative relapse and an immunosuppressive microenvironment. Various preclinical studies are exploring strategies to overcome the above challenges. Mobilization of endogenous immune cells is also necessary for CAR T cells to obtain their optimal therapeutic effect given the importance of the innate immune responses in the elimination of malignant tumors. In this review, we focus on the recent advances in the engineering of CAR T cell therapies to restore the immune response in solid malignancies, especially with CAR T cells acting as cellular carriers to deliver immunomodulators to tumors to mobilize the endogenous immune response. We also explored the sensitizing effects of conventional treatment approaches, such as chemotherapy and radiotherapy, on CAR T cell therapy. Finally, we discuss the combination of CAR T cells with biomaterials or oncolytic viruses to enhance the anti-tumor outcomes of CAR T cell therapies in solid tumors.

关键词: CAR T cells     immunoregulatory molecules     endogenous immune response     solid malignancies    

Decitabine induces -mediated immune responses in p53-mutated triple-negative breast cancer: a clinical

《医学前沿(英文)》 doi: 10.1007/s11684-023-1016-8

摘要: p53 is mutated in half of cancer cases. However, no p53-targeting drugs have been approved. Here, we reposition decitabine for triple-negative breast cancer (TNBC), a subtype with frequent p53 mutations and extremely poor prognosis. In a retrospective study on tissue microarrays with 132 TNBC cases, DNMT1 overexpression was associated with p53 mutations (P = 0.037) and poor overall survival (OS) (P = 0.010). In a prospective DEciTabinE and Carboplatin in TNBC (DETECT) trial (NCT03295552), decitabine with carboplatin produced an objective response rate (ORR) of 42% in 12 patients with stage IV TNBC. Among the 9 trialed patients with available TP53 sequencing results, the 6 patients with p53 mutations had higher ORR (3/6 vs. 0/3) and better OS (16.0 vs. 4.0 months) than the patients with wild-type p53. In a mechanistic study, isogenic TNBC cell lines harboring DETECT-derived p53 mutations exhibited higher DNMT1 expression and decitabine sensitivity than the cell line with wild-type p53. In the DETECT trial, decitabine induced strong immune responses featuring the striking upregulation of the innate immune player IRF7 in the p53-mutated TNBC cell line (upregulation by 16-fold) and the most responsive patient with TNBC. Our integrative studies reveal the potential of repurposing decitabine for the treatment of p53-mutated TNBC and suggest IRF7 as a potential biomarker for decitabine-based treatments.

关键词: p53 mutation     triple-negative breast cancer     decitabine     DNMT1     IRF7     innate immune response    

Improved dissolution and anti-inflammatory effect of ibuprofen by solid dispersion

null

《医学前沿(英文)》 2012年 第6卷 第2期   页码 195-203 doi: 10.1007/s11684-012-0189-3

摘要:

The purpose of this study was to improve the dissolution rate and anti-inflammatory effect of ibuprofen by a solid dispersion (SD) method. Initial screening was developed based on drug solubility in carriers in the liquid state to select a suitable water-soluble carrier system for the preparation of SDs. The dissolution of ibuprofen in urea was higher than in PEG4000 or mannitol. Thus, urea was selected as the carrier for the preparation of SDs. SDs were characterized in terms of dissolution, differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy. Solid dispersion-based (SDBT) and conventional (CT) tablets were prepared by the wet granulation method. The anti-inflammatory effect of SDBT was evaluated using the mouse ear edema test with xylene. In vitro release results indicated that the ibuprofen dissolution rate was improved by the SD. SD characterization results suggested that ibuprofen partly precipitates in crystalline and amorphous forms after SD preparation and that ibuprofen and urea do not interact. SDBT displayed more significant anti-inflammatory effects than CT. The dissolution rate and anti-inflammatory effect of ibuprofen were significantly enhanced by the ibuprofen-urea SD.

关键词: ibuprofen     solid dispersion     physical mixture     dissolution     anti-inflammatory effect    

Beneficial metabolic activities of inflammatory cytokine interleukin 15 in obesity and type 2 diabetes

null

《医学前沿(英文)》 2015年 第9卷 第2期   页码 139-145 doi: 10.1007/s11684-015-0377-z

摘要:

In obesity, chronic inflammation is believed to induce insulin resistance and impairs adipose tissue function. Although this view is supported by a large body of literature, it has been challenged by growing evidence that pro-inflammatory cytokines may favor insulin sensitivity through induction of energy expenditure. In this review article, interleukin 15 (IL-15) is used as a new example to explain the beneficial effects of the pro-inflammatory cytokines. IL-15 is secreted by multiple types of cells including macrophages, neutrophils and skeletal muscle cells. IL-15 expression is induced in immune cells by endotoxin and in muscle cells by physical exercise. Its transcription is induced by transcription factor NF-κB. IL-15 binds to its receptor that contains three different subunits (α, β and γ) to activate JAK/STAT, PI3K/Akt, IKK/NF-κB and JNK/AP1 pathways in cells. In the regulation of metabolism, IL-15 reduces weight gain without inhibiting food intake in rodents. IL-15 suppresses lipogenesis, stimulates brown fat function, improves insulin sensitivity through weight loss and energy expenditure. In human, circulating IL-15 is negatively associated with body weight. In the immune system, IL-15 stimulates proliferation and differentiation of T cells, NK cells, monocytes and neutrophils. In the anti-obesity effects of IL-15, T cells and NK cells are not required, but leptin receptor is required. In summary, evidence from human and rodents supports that the pro-inflammatory cytokine IL-15 may enhance energy expenditure to protect the body from obesity and type 2 diabetes. The mechanism of IL-15 action remains to be fully uncovered in the regulation of energy expenditure.

关键词: inflammation     obesity     cytokine     energy expenditure     insulin resistance    

Immunological and virological characteristics of human immunodeficiency virus type 1 superinfection: implications in vaccine design

null

《医学前沿(英文)》 2017年 第11卷 第4期   页码 480-489 doi: 10.1007/s11684-017-0594-8

摘要:

Superinfection is frequently detected among individuals infected by human immunodeficiency virus type I (HIV-1). Superinfection occurs at similar frequencies at acute and chronic infection stages but less frequently than primary infection. This observation indicates that the immune responses elicited by natural HIV-1 infection may play a role in curb of superinfection; however, these responses are not sufficiently strong to completely prevent superinfection. Thus, a successful HIV-1 vaccine likely needs to induce more potent and broader immune responses than those elicited by primary infection. On the other hand, potent and broad neutralization responses are more often detected after superinfection than during monoinfection. This suggests that broadly neutralizing antibodies are more likely induced by sequential immunization of multiple different immunogens than with only one form of envelope glycoprotein immunogens. Understanding why the protection from superinfection by immunity induced by primary infection is insufficient and if superinfection can lead to cross-reactive immune responses will be highly informative for HIV-1 vaccine design.

关键词: human immunodeficiency virus type I     superinfection     incidence     immune response    

标题 作者 时间 类型 操作

Non-genetic mechanisms of diabetic nephropathy

null

期刊论文

Persistence of humoral and cellular immune response after SARS-CoV-2 infection: opportunities and challenges

Tangchun Wu

期刊论文

Liver-directed treatment is associated with improved survival and increased response to immune checkpoint

期刊论文

Hyperthermia on skin immune system and its application in the treatment of human papillomavirus-infected

null

期刊论文

Immune response triggered by the ablation of hepatocellular carcinoma with nanosecond pulsed electric

Jianpeng Liu, Xinhua Chen, Shusen Zheng

期刊论文

Integrated analysis of gut microbiome and host immune responses in COVID-19

期刊论文

Universal influenza virus vaccines: what can we learn from the human immune response following exposure

null

期刊论文

Metformin and metabolic diseases: a focus on hepatic aspects

null

期刊论文

Heterologous expression of signal protein 14-3-3 in and the subsequent immune response in mice

ZHENG Meijuan, SHEN Jilong, LUO Qingli, XU Yuanhong

期刊论文

Construction and humoral immune response of Epstein-Barr virus latent membrane protein 2 DNA vaccine

Jianqing PAN PhD, Qin ZHANG MD, Daowen WANG MD, PhD,

期刊论文

Programming CAR T cells to enhance anti-tumor efficacy through remodeling of the immune system

Xiaohui Wang, Zhiqiang Wu, Wei Qiu, Ping Chen, Xiang Xu, Weidong Han

期刊论文

Decitabine induces -mediated immune responses in p53-mutated triple-negative breast cancer: a clinical

期刊论文

Improved dissolution and anti-inflammatory effect of ibuprofen by solid dispersion

null

期刊论文

Beneficial metabolic activities of inflammatory cytokine interleukin 15 in obesity and type 2 diabetes

null

期刊论文

Immunological and virological characteristics of human immunodeficiency virus type 1 superinfection: implications in vaccine design

null

期刊论文