Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina

Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.

Progress,implications,and challenges in using humanized immune system mice in CAR-T therapy-Application evaluation and improvement

In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking the human immune system and the tumor immune microenvironment,compared to traditional immunodeficient mice.To better promote the application of HIS mice in preclinical research,we se-lectively summarize the current prevalent and breakthrough research and evaluation of chimeric antigen receptor(CAR)-T cells in various antiviral and antitumor treat-ments.By exploring its application in preclinical research,we find that it can better reflect the actual clinical patient condition,with the advantages of providing high-efficiency detection indicators,even for progressive research and development.We believe that it has better clinical patient simulation and promotion for the updated design of CAR-T cell therapy than directly transplanted immunodeficient mice.The characteristics of the main models are proposed to improve the use defects of the existing models by reducing the limitation of antihost reaction,combining multiple models,and unifying sources and organoid substitution.Strategy study of relapse and toxicity after CAR-T treatment also provides more possibilities for application and development.

Unraveling colorectal cancer prevention:The vitamin D-gut flora-immune system nexus

Colorectal cancer(CRC)is one of the most common cancers diagnosed in the world.Although environmental and genetic factors play a major role in the pathogenesis of CRC,extensive research has suggested that vitamin D may play a pivotal role in the development of CRC.Vitamin D,primarily obtained through sunlight exposure,dietary sources,and supplements,has long been recognized for its essential functions in maintaining health,including immune regulation.This article delves into the intricate relationship between vitamin D,the immune system,gut flora,and the prevention of CRC.It presents a synthesis of epidemiological data,experimental studies,and clinical trials,highlighting the mechanisms by which vitamin D influences immune cell function,cytokine production,and inflammation.By enhancing the immune system’s surveillance and antitumor activity,vitamin D may offer a promising avenue for CRC prevention.Furthermore,this comprehensive review delves into the prospective clinical applications of vitamin D supplementation and delineates the forthcoming avenues of research in this dynamic domain.Additionally,the paper tentatively outlines a spectrum of prophylactic impacts of vitamin D on CRC,emphasizing its significant potential in reducing CRC risk through shedding light on its mechanisms,encompassing antineoplastic mechanisms,influences on the immune system,and modulation of the gut microbiome.

Efficacy of probiotics supplementation in amelioration of celiac disease symptoms and enhancement of immune system

Patients with celiac disease(CD)have a mucosal layer that is unable to regulate the gut microbiota,leaving the host vulnerable to dangerous infections and antigens.When compared to healthy people,this dysbiosis is marked by a decrease in intra-and intergeneric biodiversity,which demonstrates an imbalance between helpful bacteria and possibly harmful or proinflammatory species.The early gut microbiota is influenced by the genotype of newborns with the HLADQ2 haplotypes,and this may modify how gluten is handled in the intestinal lumen,polarize innate or adaptive immune responses,and result in glutensensitive enteropathy.The outcome of gluten digestion can vary depending on the composition of the intestinal gut bacteria and the partial conversion of gluten into peptides larger than ten amino acids in the small intestines,which can be immunogenic.In the small intestine,114 different bacterial strains belonging to 32 different species have 27 of them exhibiting peptidolytic activity.Thus,the individual risk of developing a gluten-related illness is further influenced by microbial composition and gluten degrading capacity.The conclusion that lactobacilli and Bifidobacterium spp.may be used as a probiotic supplement in CD patients is based on their shared possession of the most extensive peptidolytic and proteolytic activity thought to be engaged in the breakdown of gluten among all potential bacterial genera present in the gut microbiota.In children with CD autoimmunity,daily oral dose of Lactobacillus.plantarum HEAL9 and Lactobacillus.paracasei 8700:2 was found to modify the peripheral immune response.Bifidobacterium.breve strains have demonstrated a beneficial effect on reducing pro-inflammatory cytokine TNF-production in CD children on gluten-free diets.

Network Pharmacology, Molecular Docking and Experimental Exploring Molecular Mechanisms of Yinqiao Anti-Epidemic Formula in Regulating Mucosal Immune System of Respiratory Tract

[Objectives]To explore the molecular mechanisms of Yinqiao anti-epidemic formula(YQAEF)in regulating mucosal immune system of respiratory tract.[Methods]The active components of YQAEF were obtained from the TCMSP database,and RMIS targets were obtained from the GeneCards database.A"YQAEF components-RMIS targets-pathways"network was constructed by analyzing the above data to screen core targets for molecular docking verification.A mouse model of acute upper respiratory tract infection(AURI)was developed.Based on the experimental models,the key pathway target genes screened by network pharmacology were verified in vivo.[Results]The main active components of YQAEF involved in the regulation of the RMIS included quercetin,acetic acid,and raffinose.Key targets,such as angiotensin-converting enzyme(ACE),galactosidase alpha(GLA),matrix metalloproteinase 2(MMP2),Serpin Family E Member 1(SERPINE1),and myeloperoxidase(MPO)and important viral infection and endocrine resistance signaling pathways were included in the regulation of the RMIS with YQAEF.Molecular docking assays showed that the key targets had good binding activities with the components of YQAEF.Based on the results of network pharmacology,key target proteins in ACE,GLA,MMP2,SERPINE1,and MPO were selected for experimental verification.The results showed that ACE/ACE2 and MPO expressions were increased in the oral and throat mucosa of the AURI mice.Under YQAEF treatment,the expression levels of ACE/ACE2 and MPO were decreased.[Conclusions]This study revealed the mechanism of YQAEF in the regulation of RMIS,which is associated with multiple components,targets,and pathways.Further experiments confirmed that YQAEF interfered with MPO and ACE/ACE2 signaling pathways to regulate the RMIS in the oral and throat mucosa tissue of mice with AURI,and provide a new direction for exploring the potential antiviral mechanism of YQAEF.

The Influence of Noni Fruit Juice on Immune System Function

Morinda citrifolia (noni) fruit juice has the potential to influence immune system function. This review discusses results from several human and animal studies that provide insight into the potential mechanisms of action by which noni juice exerts its immunomodulatory effects. Increased natural killer cell activity is a likely a major contributor to the improved health outcomes and increased survival times described in case reports and as observed in LLC and S180 tumor bearing mice. Increased interferon-gamma (IFN-γ) production is also an important mechanism of action through which noni improves immune function. IFN-γ promotes natural killer cell activity and phagocytosis, activities both seen in human and bovine studies as well as in rodents. Noni promotes regulatory cytokine expression, such as IL-2 which stimulates CD4+ T cell differentiation. Noni juice appears to influence this process via kinase 1/2 (ERK1/2), protein kinase B (Akt) and nuclear factor-kappa-beta signaling. As oxidative status is known to influence immune function, this review also discusses the notable antioxidant properties of noni juice that have been demonstrated in human trials.

Fat:A matter of disturbance for the immune system

Obesity is increasingly being recognized as a risk factor for a number of benign and malignant gastrointestinal conditions. However, literature on the underlying pathophysiological mechanisms is sparse and ambiguous. There is compelling evidence that both overnutrition and undernutrition negatively interfere with the immune system. Overnutrition has been found to increase susceptibility to the development of inflammatory diseases, autoimmune diseases and cancer. In the regulation of immune and in? ammatory processes, white adipose tissue plays a critical role, not only as an energy store but also as an important endocrine organ. The obese state is characterised by a low-grade systemic in? ammation, mainly as a result of increased adipocytes as well as fat resident-and recruited-macrophage activity. In the past few years, various products of adipose tissue including adipokines and cytokines have been characterised and a number of pathways linking adipose tissue metabolism with the immune system have been identified. Activation of the innate immune system plays a major role in hepatic steatosis. Non-alcoholic fatty liver disease includes a wide spectrum of diseases, from pure steatosis to non-alcoholic steato-hepatitis in the absence of signif icant alcohol consumption. Although steatosis is considered a non-progressive disease, non-alcoholic steatohepatitis may deteriorate in advanced chronic liver diseases, cirrhosis, and hepatocellular carcinoma. An important parallel between obesityrelated pathology of adipose tissue and liver pertains to the emerging role of macrophages, and growing evidence suggests that Kupffer cells critically contribute to progression of non-alcoholic fatty liver disease. Moreover, a close link between specif ic immune activation and atherosclerosis has been well established, suggesting that fat can directly trigger immune responses. This review discusses the role of fat as "a matter of disturbance for the immune system" with a focus on hepatic steatosis.

The mucosal immune system in the oral cavity——an orchestra of T cell diversity

The mucosal immune system defends against a vast array of pathogens, yet it exhibits limited responses to commensal microorganisms under healthy conditions. The oral-pharyngeal cavity, the gateway for both the gastrointestinal and respiratory tracts, is composed of complex anatomical structures and is constantly challenged by antigens from air and food. The mucosal immune system of the oral-pharyngeal cavity must prevent pathogen entry while maintaining immune homeostasis, which is achieved via a range of mechanisms that are similar or different to those utilized by the gastrointestinal immune system. In this review, we summarize the features of the mucosal immune system,focusing on T cell subsets and their functions. We also discuss our current understanding of the oral-pharyngeal mucosal immune system.

Dynamic route guidance algorithm based onartificial immune system

To improve the performance of the K-shortest paths search in intelligent traffic guidance systems, this paper proposes an optimal search algorithm based on the intelligent optimization search theory and the metaphor mechanism of vertebrate immune systems. This algorithm, applied to the urban traffic network model established by the node-expanding method, can expediently realize K-shortest paths search in the urban traffic guidance systems. Because of the immune memory and global parallel search ability from artificial immune systems, K shortest paths can be found without any repeat, which indicates evidently the superiority of the algorithm to the conventional ones. Not only does it perform a better parallelism, the algorithm also prevents premature phenomenon that often occurs in genetic algorithms. Thus, it is especially suitable for real-time requirement of the traffic guidance system and other engineering optimal applications. A case study verifies the efficiency and the practicability of the algorithm aforementioned.

A Robust Damage Detection Method Developed for Offshore Jacket Platforms Using Modified Artificial Immune System Algorithm

Steel jacket-type platforms are the common kind of the offshore structures and health monitoring is an important issue in their safety assessment. In the present study, a new damage detection method is adopted for this kind of structures and inspected experimentally by use of a laboratory model. The method is investigated for developing the robust damage detection technique which is less sensitive to both measurement and analytical model uncertainties. For this purpose, incorporation of the artificial immune system with weighted attributes （AISWA） method into finite element （FE） model updating is proposed and compared with other methods for exploring its effectiveness in damage identification. Based on mimicking immune recognition, noise simulation and attributes weighting, the method offers important advantages and has high success rates. Therefore, it is proposed as a suitable method for the detection of the failures in the large civil engineering structures with complicated structural geometry, such as the considered case study.

Gut microbiota and immune system in liver cancer:Promising therapeutic implication from development to treatment

Liver cancer is a leading cause of death worldwide,and hepatocellular carcinoma(HCC)is the most frequent primary liver tumour,followed by cholangiocarcinoma.Notably,secondary tumours represent up to 90% of liver tumours.Chronic liver disease is a recognised risk factor for liver cancer development.Up to 90% of the patients with HCC and about 20% of those with cholangiocarcinoma have an underlying liver alteration.The gut microbiota-liver axis represents the bidirectional relationship between gut microbiota,its metabolites and the liver through the portal flow.The interplay between the immune system and gut microbiota is also well-known.Although primarily resulting from experiments in animal models and on HCC,growing evidence suggests a causal role for the gut microbiota in the development and progression of chronic liver pathologies and liver tumours.Despite the curative intent of“traditional”treatments,tumour recurrence remains high.Therefore,microbiota modulation is an appealing therapeutic target for liver cancer prevention and treatment.Furthermore,microbiota could represent a non-invasive biomarker for early liver cancer diagnosis.This review summarises the potential role of the microbiota and immune system in primary and secondary liver cancer development,focusing on the potential therapeutic implications.

Clone Selection Algorithm with Niching Strategy for Computer Immune System

A clone selection algorithm for computer immune system is presented. Clone selection principles in biological immune system are applied to the domain of computer virus detection. Based on the negative selection algorithm proposed by Stephanie Forrest, combining mutation operator in genetic algorithms and niching strategy in biology is adopted, the number of detectors is decreased effectively and the ability on self-nonself discrimination is improved. Simulation experiment shows that the algorithm is simple, practical and is adapted to the discrimination for long files.

A Novel Immune System Model and Its Application to Network Intrusion Detection

Based on analyzing the techniques and architecture of existing network Intrusion Detection System (IDS), and probing into the fundament of Immune System (IS), a novel immune model is presented and applied to network IDS, which is helpful to design an effective IDS. Besides, this paper suggests a scheme to represent the self profile of network. And an automated self profile extraction algorithm is provided to extract self profile from packets. The experimental results prove validity of the scheme and algorithm, which is the foundation of the immune model.

Hybrid artificial immune system and extremal optimization algorithm for permutation flowshop scheduling problem

The permutation flowshop scheduling problem （PFSP） is one of the most well-known and well-studied production scheduling problems with strong industrial background. This paper presents a new hybrid optimization algorithm which combines the strong global search ability of artificial immune system （AIS） with a strong local search ability of extremal optimization （EO） algorithm. The proposed algorithm is applied to a set of benchmark problems with a makespan criterion. Performance of the algorithm is evaluated. Comparison results indicate that this new method is an effective and competitive approach to the PFSP.

Modelling Immune System:Principles,Models,Analysis and Perspectives

The biological immune system is a complex adaptive system.There are lots of benefits for building the model of the immune system.For biological researchers,they can test some hypotheses about the infection process or simulate the responses of some drugs.For computer researchers,they can build distributed,robust and fault tolerant networks inspired by the functions of the immune system.This paper provides a comprehensive survey of the literatures on modelling the immune system.From the methodology perspective,the paper compares and analyzes the existing approaches and models,and also demonstrates the focusing research effort on the future immune models in the next few years.

Stochastic responses of tumor-immune system with periodic treatment

We investigate the stochastic responses of a tumor–immune system competition model with environmental noise and periodic treatment. Firstly, a mathematical model describing the interaction between tumor cells and immune system under external fluctuations and periodic treatment is established based on the stochastic differential equation. Then, sufficient conditions for extinction and persistence of the tumor cells are derived by constructing Lyapunov functions and Ito＇s formula. Finally, numerical simulations are introduced to illustrate and verify the results. The results of this work provide the theoretical basis for designing more effective and precise therapeutic strategies to eliminate cancer cells, especially for combining the immunotherapy and the traditional tools.

Effect of bacteriocin-producing Pediococcus acidilactici strains on the immune system and intestinal flora of normal mice

This study was performed to determine the effects of bacteriocin-producing and non-bacteriocin-producing Pediococcus acidilactici strains on the immune system and intestinal flora of normal mice.Two P.acidilactici strains with antibacterial activity(P.acidilactici CCFM28 and CCFM18)were obtained based on the inhibition-zone assay.The produced components were identified as bacteriocins through protease treatment,pH adjustment and hydrogen peroxide treatment.Bacteriocin-producing and non-bacteriocin-producing P.acidilactici strains(P.acidilactici CCFM28,CCFM18 and NT17-3)caused significant changes in serum immune factors and intestinal flora of normal mice.After 14 days of intervention,the relative abundance of Firmicutes was significantly decreased,but that of Proteobacteria was significantly increased at the phylum level.At the genus level,the administration of three P.acidilactici strains resulted in the downregulation of Blautia and the upregulation of Ruminococcus and Lactobacillus.Furthermore,there were also different regulations on some probiotic strains,such as Bifidobacterium,Coprococcus and Akkermansia,which were closely related to the antibacterial ability of the bacteriocin and the type of strain.The results indicated that the intervention of different P.acidilactici strains could differently change the structure of intestinal flora in normal mice,which provided theoretical guidance for the selective use of bacteriocin-producing strains for health regulation in the future.

Induction of apoptosis of lymphocytes in ratmucosalimmune system

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A Review of Artificial Immune System Based Security Frameworks for MANET

Mobile ad hoc networks (MANETs) are collections of wireless mobile devices that form a communication network with restricted broadcast range, limited resources and without fixed infrastructure. Routing is a critical function in multi-hop MANETs. At the same time, security in MANETs—especially routing security—presents a number of new and interesting challenges. Communication is achieved by relaying data along routes that are dynamically discovered and maintained through collaboration between the nodes. Advances in the field of artificial immune systems provide an opportunity to improve MANET security and performance. Artificial immune systems mimic the functionality of the human immune system wherein there is clear distinction between self and non self and this delineation is important in a MANET where there is no centralized management. The high level of protection provided to the human body by an evolved immune system can be applied as a security feature in MANET. The current security techniques proposed for MANET have varying degrees of success due to the dynamic nature of a MANET. This paper will review different strategies for the application of artificial immune systems to MANETs.

Combining Artificial Immune System and Clustering Analysis: A Stock Market Anomaly Detection Model

Artificial intelligence research in the stock market sector has been heavily geared towards stock price prediction rather than stock price manipulation. As online trading systems have increased the amount of high volume and re-al-time data transactions, the stock market has increased vulnerability to at-tacks. This paper aims to detect these attacks based on normal trade behavior using an Artificial Immune System (AIS) approach combined with one of four clustering algorithms. The AIS approach is inspired by its proven ability to handle time-series data and its ability to detect abnormal behavior while only being trained on regular trade behavior. These two main points are essential as the models need to adapt over time to adjust to normal trade behavior as it evolves, and due to confidentiality and data restrictions, real-world manipula-tions are not available for training. This paper discovers a competitive alterna-tive to the leading approach and investigates the effects of combining AIS with clustering algorithms;Kernel Density Estimation, Self-Organized Maps, Densi-ty-Based Spatial Clustering of Applications with Noise and Spectral clustering. The best performing solution achieves leading performance using common clustering metrics, including Area Under the Curve, False Alarm Rate, False Negative Rate, and Computation Time.