Human tumor cell‐specific antibodies were induced in mice after immunization with a synthetic glycopeptide, which is based on the GM2 ganglioside carbohydrate moiety produced on a gram scale in bacteria. Such neoglycopeptides represent a promising cancer vaccine strategy for active immunotherapy targeting carbohydrates.
We demonstrate the power of using symmetries for model selection in the context of mechanistic modelling. We analyse two different models called the power law model (PLM) and the immunological model (IM) describing the increase in cancer risk with age, due to mutation accumulation or immunosenescence, respectively. The IM fits several cancer types better than the PLM implying that it would be selected based on minimizing residuals. However, recently a symmetry-based method for model selection has been developed, which has been successfully used in an in silico setting to find the correct model when traditional model fitting has failed. Here, we apply this method in a real-world setting to investigate the mechanisms of carcinogenesis. First, we derive distinct symmetry transformations of the two models and then we select the model which not only fits the original data but is also invariant under transformations by its symmetry. Contrary to the initial conclusion, we conclude that the PLM realistically describes the mechanism underlying the colon cancer dataset. These conclusions agree with experimental knowledge, and this work demonstrates how a model selection criterion based on biological properties can be implemented using symmetries. 相似文献
The cocoa, as part of the wonderful nature, provides the mankind a wide variety of valuable food products and health benefits. The most known and universally relished product derived from this fruit is chocolate, an amazing and unique food for the human nutrition with records of consumption of similar products dating to 1000 years BC. In fact, the cocoa is a complex food that includes over 300 different components. This review is designed to inform scientists, technicians, academicians, farmers, and interested communities of numerous studies that have been conducted worldwide to investigate the properties of various cocoa constituents, their relations to human health, and their potential role in the prevention and treatment of many medical conditions. The general population, for example in Brazil, despite being one of the major producers of cocoa, is poorly informed of the significant and beneficial properties of cocoa. The present review covers important topics linking cocoa to human health and show the state of the art of effect of cocoa in different systems that comprise the human body. The paper is organized based on the main human organ system and includes: cardiovascular/circulatory, neurological/nervous, oral health, endocrine, lymphatic and immunological, respiratory, reproductive, and dermatological systems. Scientific findings tend to confirm the historic designation of cocoa as “food of the Gods.” 相似文献
(1) Liver regeneration following partial hepatectomy for colorectal liver metastasis (CRLM) has been linked to tumour recurrence. Inhibition of the renin–angiotensin system (RASi) attenuates CRLM growth in the non-regenerating liver. This study investigates whether RASi exerts an antitumour effect within the regenerating liver following partial hepatectomy for CRLM and examines RASi-induced changes in the tumour immune microenvironment; (2) CRLM in mice was induced via intrasplenic injection of mouse colorectal tumour cells, followed by splenectomy on Day 0. Mice were treated with RASi captopril (250 mg/kg/day), or saline (control) from Day 4 to Day 16 (endpoint) and underwent 70% partial hepatectomy on Day 7. Liver and tumour samples were characterised by flow cytometry and immunofluorescence; (3) captopril treatment reduced tumour burden in mice following partial hepatectomy (p < 0.01). Captopril treatment reduced populations of myeloid-derived suppressor cells (MDSCs) (CD11b+Ly6CHip < 0.05, CD11b+Ly6CLop < 0.01) and increased PD-1 expression on infiltrating hepatic tissue-resident memory (TRM)-like CD8+ (p < 0.001) and double-negative (CD4-CD8-; p < 0.001) T cells; (4) RASi reduced CRLM growth in the regenerating liver and altered immune cell composition by reducing populations of immunosuppressive MDSCs and boosting populations of PD-1+ hepatic TRMs. Thus, RASi should be explored as an adjunct therapy for patients undergoing partial hepatectomy for CRLM. 相似文献
In the past few years, the study of therapeutic RNA nanotechnology has expanded tremendously to encompass a large group of interdisciplinary sciences. It is now evident that rationally designed programmable RNA nanostructures offer unique advantages in addressing contemporary therapeutic challenges such as distinguishing target cell types and ameliorating disease. However, to maximize the therapeutic benefit of these nanostructures, it is essential to understand the immunostimulatory aptitude of such tools and identify potential complications. This paper presents a set of 16 nanoparticle platforms that are highly configurable. These novel nucleic acid based polygonal platforms are programmed for controllable self‐assembly from RNA and/or DNA strands via canonical Watson–Crick interactions. It is demonstrated that the immunostimulatory properties of these particular designs can be tuned to elicit the desired immune response or lack thereof. To advance the current understanding of the nanoparticle properties that contribute to the observed immunomodulatory activity and establish corresponding designing principles, quantitative structure–activity relationship modeling is conducted. The results demonstrate that molecular weight, together with melting temperature and half‐life, strongly predicts the observed immunomodulatory activity. This framework provides the fundamental guidelines necessary for the development of a new library of nanoparticles with predictable immunomodulatory activity. 相似文献
The ability of tumor cells to evade the immune system is one of the main challenges we confront in the fight against cancer. Multiple strategies have been developed to counteract this situation, including the use of immunostimulant molecules that play a key role in the anti-tumor immune response. Such a response needs to be tumor-specific to cause as little damage as possible to healthy cells and also to track and eliminate disseminated tumor cells. Therefore, the combination of immunostimulant molecules and tumor-associated antigens has been implemented as an anti-tumor therapy strategy to eliminate the main obstacles confronted in conventional therapies. The immunostimulant 4-1BBL belongs to the tumor necrosis factor (TNF) family and it has been widely reported as the most effective member for activating lymphocytes. Hence, we will review the molecular, pre-clinical, and clinical applications in conjunction with tumor-associated antigens in antitumor immunotherapy, as well as the main molecular pathways involved in this association. 相似文献
Celery is a frequent cause of food allergy in pollen‐sensitized patients and can induce severe allergic reactions. Clinical symptoms cannot be predicted by skin prick tests (SPTs) or by determining allergen‐specific immunoglobulin E (IgE). Our aim was to identify specific IgE binding peptides by using an array technique. For our study, the sera of 21 patients with positive double‐blind, placebo‐controlled food challenge (DBPCFC) to celery, as well as the sera of 17 healthy patients were used. Additionally, all patients underwent skin tests along with determinations of specific IgE binding. The major allergen of celery Api g 1.0101 (Apium graveolens) was synthesized as an array of overlapping peptides and probed with the patients' sera. We developed an improved immunoassay protocol by investigating peptide lengths, peptide densities, incubation parameters, and readout systems, which could influence IgE binding. Sera of celery‐allergic patients showed binding to three distinct regions of Api g 1.0101. The region including amino acids 100 to 126 of Api g 1.0101 is the most important region for IgE binding. This region caused a fivefold higher binding of IgE from the sera of celery‐allergic patients compared to those of healthy individuals. In particular, one peptide (VLVPTADGGSIC) was recognized by all sera of celery‐allergic patients. In contrast, no binding to this peptide was detected in sera of the healthy controls. Our improved assay strategy allows us to distinguish between celery‐allergic and healthy individuals, but needs to be explored in a larger cohort of well‐defined patients.相似文献
In cellular signal transduction, scaffold proteins provide binding sites to organize signaling proteins into supramolecular complexes and act as nodes in the signaling network. Furthermore, multivalent interactions between the scaffold and other signaling proteins contribute to the formation of protein microclusters. Such microclusters are prominent in early T cell signaling. Here, we explored the minimal structural requirement for a scaffold protein by coupling multiple copies of a proline‐rich peptide corresponding to an interaction motif for the SH3 domain of the adaptor protein GADS to an N‐(2‐hydroxypropyl)methacrylamide polymer backbone. When added to GADS‐containing cell lysates, these scaffolds (but not individual peptides) promoted the binding of GADS to peptide microarrays. This can be explained by the cross‐linking of GADS into larger complexes. Furthermore, following import into Jurkat T cell leukemia cells, this synthetic scaffold enhanced the formation of microclusters of signaling proteins. 相似文献
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