Mitochondria play a crucial role as organelles,managing several physiological processes such as redox balance,cell metabolism,and energy synthesis.Initially,the assumption was that mitochondria primarily resided in th...Mitochondria play a crucial role as organelles,managing several physiological processes such as redox balance,cell metabolism,and energy synthesis.Initially,the assumption was that mitochondria primarily resided in the host cells and could exclusively transmit from oocytes to offspring by a mechanism known as vertical inheritance of mitochondria.Recent scholarly works,however,suggest that certain cell types transmit their mitochondria to other developmental cell types via a mechanism referred to as intercellular or horizontal mitochondrial transfer.This review details the process of which mitochondria are transferred across cells and explains the impact of mitochondrial transfer between cells on the efficacy and functionality of cancer cells in various cancer forms.Specifically,we review the role of mitochondria transfer in regulating cellular metabolism restoration,excess reactive oxygen species(ROS)generation,proliferation,invasion,metastasis,mitophagy activation,mitochondrial DNA(mtDNA)inheritance,immune system modulation and therapeutic resistance in cancer.Additionally,we highlight the possibility of using intercellular mitochondria transfer as a therapeutic approach to treat cancer and enhance the efficacy of cancer treatments.展开更多
The gut microbiome is a complex community of microorganisms that plays a direct role in the health of both the gastrointestinal tract and the entire body.Numerous factors influence the abundance and diversity of gut m...The gut microbiome is a complex community of microorganisms that plays a direct role in the health of both the gastrointestinal tract and the entire body.Numerous factors influence the abundance and diversity of gut microbiota.Microbial imbalance can contribute to disease development.Probiotics are biologically active supplements with promising properties that have high therapeutic potential.Currently,there is a tendency to switch from classic probiotic microorganisms represented by lactic acid bacteria to next-generation probiotics due to their unique ability to influence the human immune system.New-generation probiotics include bacteria such as Akkermansia muciniphila,Faecalibacterium prausnitzii,Bacteroides sp.,Prevotella sp.,Roseburia sp.,and Eubacterium sp.Nextgeneration probiotics can affect host immune cells by secreting various substances,such as butyrate in F.prausnitzii,or through interaction with Toll-like receptors of intestinal epithelial cells,such as A.muciniphila.Studying the role of next-generation probiotics in immune regulation is a promising area of research.This study describes the interactions of next-generation probiotics with the immune system.Understanding the mechanisms of such interactions will improve the treatment of various diseases.展开更多
Mood disorders include a set of psychiatric manifestations of increasing prevalence in our society,being mainly represented by major depressive disorder(MDD)and bipolar disorder(BD).The etiopathogenesis of mood disord...Mood disorders include a set of psychiatric manifestations of increasing prevalence in our society,being mainly represented by major depressive disorder(MDD)and bipolar disorder(BD).The etiopathogenesis of mood disorders is extremely complex,with a wide spectrum of biological,psychological,and sociocultural factors being responsible for their appearance and development.In this sense,immune system dysfunction represents a key mechanism in the onset and pathophysiology of mood disorders,worsening mainly the central nervous system(neuroinflammation)and the periphery of the body(systemic inflammation).However,these alterations cannot be understood separately,but as part of a complex picture in which different factors and systems interact with each other.Psychoneuroimmunoendocrinology(PNIE)is the area responsible for studying the relationship between these elements and the impact of mind–body integration,placing the immune system as part of a whole.Thus,the dysfunction of the immune system is capable of influencing and activating different mechanisms that promote disruption of the psyche,damage to the nervous system,alterations to the endocrine and metabolic systems,and disruption of the microbiota and intestinal ecosystem,as well as of other organs and,in turn,all these mechanisms are responsible for inducing and enhancing the immune dysfunction.Similarly,the clinical approach to these patients is usually multidisciplinary,and the therapeutic arsenal includes different pharmacological(for example,antidepressants,antipsychotics,and lithium)and non-pharmacological(i.e.,psychotherapy,lifestyle,and electroconvulsive therapy)treatments.These interventions also modulate the immune system and other elements of the PNIE in these patients,which may be interesting to understand the therapeutic success or failure of these approaches.In this sense,this review aims to delve into the relationship between immune dysfunction and mood disorders and their integration in the complex context of PNIE.Likewise,an attempt will be made to explore the effects on the immune system of different strategies available in the clinical approach to these patients,in order to identify the mechanisms described and their possible uses as biomarkers.展开更多
Germ-free mice exhibit profound immunological immaturity.Despite recent studies emphasizing the role of specific bacterium-derived metabolites in immune cell development and differentiation,the mechanisms linking micr...Germ-free mice exhibit profound immunological immaturity.Despite recent studies emphasizing the role of specific bacterium-derived metabolites in immune cell development and differentiation,the mechanisms linking microbiota absence to systemic immune deficits remain incompletely defined.Here,droplet-based single-cell RNA sequencing of bone marrow and peripheral blood from both germ-free and specific pathogen-free mice was performed,identifying 25 transcriptionally distinct cell types.Neutrophil apoptosis was elevated in germ-free mice,potentially due to the absence of niacin dehydrogenase,a metabolite primarily produced by Pseudomonas.In addition,germ-free mice exhibited increased excretion of 5’-methylthioadenosine,enhanced ERK activation driven by reactive oxygen species,and disruption of bone marrow stromal antigen 2 signaling.Monocytes and CD8^(+)T cells from germ-free mice showed diminished responses to interferon-β and interferon-γ,consistent with heightened viral susceptibility.These findings establish a microbiota-dependent regulatory pathway linking immunodeficiency to microbial absence in germ-free mice,confirmed through complementary validation techniques.展开更多
The tumor microenvironment(TME)is characterized by a symbiosis between cancer cells and the immune cells.The scarcity of oxygen generates hostility that forces cancer cells to alter their biological features in solid ...The tumor microenvironment(TME)is characterized by a symbiosis between cancer cells and the immune cells.The scarcity of oxygen generates hostility that forces cancer cells to alter their biological features in solid tumors.In response to low oxygen availability,the Hypoxia Inducible Factors(HIF-1/2/3α)act as metabolic mediators,producing extracellular metabolites in the tumor microenvironment that influence the immune cells.The modulation of lactate and adenosine on immune evasion has been widely described;however,under hypoxic conditions,it has been barely addressed.Evidence has demonstrated an interplay between cancer and the immune cells,and the present review explores thefindings that support HIFs bridging the gap between the rise of these metabolites and the immunosurveillance failure in a hypoxic context.Moreover,new insights based on systemic oxygen administration are discussed,which might counterbalance the effect mediated by lactate and adenosine,to recover anti-tumor immunity.Thus,the disruption of anti-tumor immunity has been the focus of recent research and this novel avenue opens therapeutic vulnerabilities that can be useful for cancer patients.展开更多
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 und...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.展开更多
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 ma...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.展开更多
Recent research has highlighted the potential of Codonopsis Radix to modulate the immune system,making it a promising candidate for treating chronic inflammatory and cardiovascular diseases,tumors,and aging.However,be...Recent research has highlighted the potential of Codonopsis Radix to modulate the immune system,making it a promising candidate for treating chronic inflammatory and cardiovascular diseases,tumors,and aging.However,because of the complex immune activities of its various components,a comprehensive understanding of Codonopsis Radix immune-regulating properties is still lacking.This knowledge gap hinders its widespread utilization in clinical practice.Therefore,this review aimed to assess the impact of Codonopsis Radix on the immune system and elucidate its underlying mechanisms.Additionally,we compared the immunomodulatory effects of different active ingredients derived from Codonopsis Radix to provide a theoretical basis for future investigations on immunomodulation.展开更多
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 ...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.展开更多
Smoking has a complex impact on the immune system, affecting both innate and adaptive immunity. It can exacerbate pathogenic immune responses and attenuate defensive immunity, leading to a higher susceptibility to inf...Smoking has a complex impact on the immune system, affecting both innate and adaptive immunity. It can exacerbate pathogenic immune responses and attenuate defensive immunity, leading to a higher susceptibility to infections and certain diseases. The chemicals in cigarette smoke, such as nicotine and carbon monoxide, can alter immune cell functions and inflammatory responses. Smoking can also have long-term effects on the immune system, with some changes persisting even after quitting [1]. According to a Penn Medicine Physician, the Medical Oncologist Dr. David Porter, “People who are smokers tend to get sicker from infections”, “It may be that smoking impacts the immune system’s ability to respond appropriately”. Thus, such individuals within smoking exposure history might be considered as immunocompromised due to the altered and weakened immune system. Cigarette smoking is a prevalent habit with far-reaching health implications. Among its many adverse effects, smoking significantly alters the immune system’s functionality [1].展开更多
The immune system operates as a complex organization with distinct roles and functions. Excitingly we recognized the similarities between the cellular dynamics of the immune system and our lives, activities, and behav...The immune system operates as a complex organization with distinct roles and functions. Excitingly we recognized the similarities between the cellular dynamics of the immune system and our lives, activities, and behaviors. Observing the immune system can guide how to respond to various daily situations, including when to react, tolerate, or ignore. Recognizing this analogy between our lives and the immune system should motivate us to adopt a wisdom-based approach when investigating the mechanisms and future discoveries related to this system and to deepen our understanding of this complex system with newfound respect. In this context, the present review examines several integral biological processes of the immune system by drawing parallels between them and human life, activities, and behaviors to learn how we must behave based on the insights offered by this complex organization. The literature search was conducted in international databases such as PubMed/MEDLINE and Google Scholar search engine using English equivalent keywords from 1998 up to April 2023. The search strategy used the following subject heading terms: Immune system, analogy, human life, cellular dynamics, memory, tolerance, and ignorance. In conclusion, the immune system is a complex organization comprising various cells interacting within specific sites and networks, communicating, drawing experiences, and learning how to tolerate certain conditions that make it share certain similarities with human life.展开更多
Birds,a fascinating and diverse group occupying various habitats worldwide,exhibit a wide range of life-history traits,reproductive methods,and migratory behaviors,all of which influence their immune systems.The assoc...Birds,a fascinating and diverse group occupying various habitats worldwide,exhibit a wide range of life-history traits,reproductive methods,and migratory behaviors,all of which influence their immune systems.The association between major histocompatibility complex(MHC)genes and certain ecological factors in response to pathogen selection has been extensively studied;however,the role of the co-working molecule T cell receptor(TCR)remains poorly understood.This study aimed to analyze the copy numbers of TCR-V genes,the selection pressure(ωvalue)on MHC genes using available genomic data,and their potential ecological correlates across 93 species from 13 orders.The study was conducted using the publicly available genome data of birds.Our findings suggested that phylogeny influences the variability in TCR-V gene copy numbers and MHC selection pressure.The phylogenetic generalized least squares regression model revealed that TCR-Vαδcopy number and MHC-I selection pressure were positively associated with body mass.Clutch size was correlated with MHC selection pressure,and Migration was correlated with TCR-Vβcopy number.Further analyses revealed that the TCR-Vβcopy number was positively correlated with MHC-IIB selection pressure,while the TCR-Vγcopy number was negatively correlated with MHC-I peptide-binding region selection pressure.Our findings suggest that TCR-V diversity is significant in adaptive evolution and is related to species’life-history strategies and immunological defenses and provide valuable insights into the mechanisms underlying TCR-V gene duplication and MHC selection in avian species.展开更多
In this paper,different kinds of enzymes,immune factors and regulatory factors of the immune system of crustaceans are summarized and then combed systematically and thoroughly. According to the mutual influence and ef...In this paper,different kinds of enzymes,immune factors and regulatory factors of the immune system of crustaceans are summarized and then combed systematically and thoroughly. According to the mutual influence and effects of these factors,different symbolic forms are introduced to express the effects,and ultimately the whole node graph of the system is obtained. The graph theory can be used for further researches on the immune system of crustacean.展开更多
Major depression during pregnancy is a common psychiatric disorder that arises from a complex and mul- tifactorial etiology. Psychosocial stress, sex, hormones, and genetic vulnerability increase the risk for triggeri...Major depression during pregnancy is a common psychiatric disorder that arises from a complex and mul- tifactorial etiology. Psychosocial stress, sex, hormones, and genetic vulnerability increase the risk for triggering mood disorders. Microglia and toll-like receptor 4 play a crucial role in triggering wide and varied stress-induced responses mediated through activation of the inflammasome; this leads to the secretion of inflammatory cytokines, increased serotonin metabolism, and reduction of neurotransmitter availability along with hypothalamic-pituitary-adrenal axis hyperactivity. Dysregulation of this intricate neu- roimmune communication network during pregnancy modifies the maternal milieu, enhancing the emergence of depressive symptoms and negative obstetric and neu- ropsychiatric outcomes. Although several studies have clearly demonstrated the role of the innate immune system in major depression, it is still unclear how the placenta, the brain, and the monoaminergic and neuroendocrine systems interact during perinatal depression. Thus, in the present review we describe the cellular and molecular interactions between these systems in major depression during preg- nancy, proposing that the same stress-related mechanisms involved in the activation of the NLRP3 inflammasome in microglia and peripheral myeloid cells in depressed patients operate in a similar fashion in the neuroimmune placenta during perinatal depression. Thus, activation of Toll-like receptor 2 and 4 signaling and the NLRP3 inflammasome in placental immune cells may promote a shift of the Thl/Th2 bias towards a predominant Thl/Thl7 inflammatory response, associated with increased secretion of pro-inflammatory cytokines, among other secreted autocrine and paracrine mediators, which play a crucial role in triggering and/or exacerbating depressive symptoms during pregnancy.展开更多
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. ...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.展开更多
The immune system plays a complex role in the development and progression of pancreatic cancer. Inflammation can promote the formation of premalignant lesions and accelerate pancreatic cancer development. Conversely, ...The immune system plays a complex role in the development and progression of pancreatic cancer. Inflammation can promote the formation of premalignant lesions and accelerate pancreatic cancer development. Conversely, pancreatic cancer is characterized by an immunosuppressive environment, which is thought to promote tumor progression and invasion. Here we review the current literature describing the role of the immune response in the progressive development of pancreatic cancer, with a focus on the mechanisms that drive recruitment and activation of immune cells at the tumor site, and our current understanding of the function of the immune cell types at the tumor. Recent clinical and preclinical data are reviewed, detailing the involvement of the immune response in pancreatitis and pancreatic cancer, including the role of specific cytokines and implications for disease outcome. Acute pancreatitis is characterized by a predominantly innate immune response, while chronic pancreatitis elicits an immune response that involves both innate and adaptive immune cells, and often results in profound sys-temic immune-suppression. Pancreatic adenocarcinoma is characterized by marked immune dysfunction driven by immunosuppressive cell types, tumor-promoting immune cells, and defective or absent inflammatory cells. Recent studies reveal that immune cells interact with cancer stem cells and tumor stromal cells, and these interactions have an impact on development and progression of pancreatic ductal adenocarcinoma(PDAC). Finally, current PDAC therapies are reviewed and the potential for harnessing the actions of the immune response to assist in targeting pancreatic cancer using immunotherapy is discussed.展开更多
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 gastroi...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.展开更多
Nutrition during perinatal period is more critical for the developme nt of the immune system than during adulthood, and the relationship between earl y nutrition and diseases in later life has been established. In hum...Nutrition during perinatal period is more critical for the developme nt of the immune system than during adulthood, and the relationship between earl y nutrition and diseases in later life has been established. In humans and labor atory animals, the plasticity of metabolic function in foetuses or neonates enab les them to adapt to malnutrition for survival; however, such an adaptation, as usually evidenced by retarded growth, stunted development of lymphoid organs and impaired immunocompetence, can maintain and persist into later life even when n utrition is improved. Early nutrition may thus programme' the immune system of a nimals. Limited experimental studies have also revealed that long-term immunity against nematode parasites in sheep can be enhanced by a short-term protein su pplementation shortly after weaning, a form of 'nutritional programming', but su ch an effect appears to vanish if the nutritional status of young animals alread y meets at least the requirement for maintenance.展开更多
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 m...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.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.:82272749)the Natural Science Foundation of Liaoning Province,China(Grant No.:2022-MS-190).
文摘Mitochondria play a crucial role as organelles,managing several physiological processes such as redox balance,cell metabolism,and energy synthesis.Initially,the assumption was that mitochondria primarily resided in the host cells and could exclusively transmit from oocytes to offspring by a mechanism known as vertical inheritance of mitochondria.Recent scholarly works,however,suggest that certain cell types transmit their mitochondria to other developmental cell types via a mechanism referred to as intercellular or horizontal mitochondrial transfer.This review details the process of which mitochondria are transferred across cells and explains the impact of mitochondrial transfer between cells on the efficacy and functionality of cancer cells in various cancer forms.Specifically,we review the role of mitochondria transfer in regulating cellular metabolism restoration,excess reactive oxygen species(ROS)generation,proliferation,invasion,metastasis,mitophagy activation,mitochondrial DNA(mtDNA)inheritance,immune system modulation and therapeutic resistance in cancer.Additionally,we highlight the possibility of using intercellular mitochondria transfer as a therapeutic approach to treat cancer and enhance the efficacy of cancer treatments.
基金carried out at the expense of a grant from the Russian Science Foundation No.24-24-20036,https://rscf.ru/project/24-24-20036(accessed on 5 June 2025).
文摘The gut microbiome is a complex community of microorganisms that plays a direct role in the health of both the gastrointestinal tract and the entire body.Numerous factors influence the abundance and diversity of gut microbiota.Microbial imbalance can contribute to disease development.Probiotics are biologically active supplements with promising properties that have high therapeutic potential.Currently,there is a tendency to switch from classic probiotic microorganisms represented by lactic acid bacteria to next-generation probiotics due to their unique ability to influence the human immune system.New-generation probiotics include bacteria such as Akkermansia muciniphila,Faecalibacterium prausnitzii,Bacteroides sp.,Prevotella sp.,Roseburia sp.,and Eubacterium sp.Nextgeneration probiotics can affect host immune cells by secreting various substances,such as butyrate in F.prausnitzii,or through interaction with Toll-like receptors of intestinal epithelial cells,such as A.muciniphila.Studying the role of next-generation probiotics in immune regulation is a promising area of research.This study describes the interactions of next-generation probiotics with the immune system.Understanding the mechanisms of such interactions will improve the treatment of various diseases.
基金supported by the Instituto de Salud Carlos III(EstataldeI+D+I2020-2027)co-financed by the European Development Regional Fund“A way to achieve Europe”P2022/BMD-7321(Comunidad de Madrid)and ProACapital,Halekulani S.L.and MJR.
文摘Mood disorders include a set of psychiatric manifestations of increasing prevalence in our society,being mainly represented by major depressive disorder(MDD)and bipolar disorder(BD).The etiopathogenesis of mood disorders is extremely complex,with a wide spectrum of biological,psychological,and sociocultural factors being responsible for their appearance and development.In this sense,immune system dysfunction represents a key mechanism in the onset and pathophysiology of mood disorders,worsening mainly the central nervous system(neuroinflammation)and the periphery of the body(systemic inflammation).However,these alterations cannot be understood separately,but as part of a complex picture in which different factors and systems interact with each other.Psychoneuroimmunoendocrinology(PNIE)is the area responsible for studying the relationship between these elements and the impact of mind–body integration,placing the immune system as part of a whole.Thus,the dysfunction of the immune system is capable of influencing and activating different mechanisms that promote disruption of the psyche,damage to the nervous system,alterations to the endocrine and metabolic systems,and disruption of the microbiota and intestinal ecosystem,as well as of other organs and,in turn,all these mechanisms are responsible for inducing and enhancing the immune dysfunction.Similarly,the clinical approach to these patients is usually multidisciplinary,and the therapeutic arsenal includes different pharmacological(for example,antidepressants,antipsychotics,and lithium)and non-pharmacological(i.e.,psychotherapy,lifestyle,and electroconvulsive therapy)treatments.These interventions also modulate the immune system and other elements of the PNIE in these patients,which may be interesting to understand the therapeutic success or failure of these approaches.In this sense,this review aims to delve into the relationship between immune dysfunction and mood disorders and their integration in the complex context of PNIE.Likewise,an attempt will be made to explore the effects on the immune system of different strategies available in the clinical approach to these patients,in order to identify the mechanisms described and their possible uses as biomarkers.
基金supported by the Science Technology and Innovation Commission of Shenzhen Municipality,China(SGCX20190919142801722)。
文摘Germ-free mice exhibit profound immunological immaturity.Despite recent studies emphasizing the role of specific bacterium-derived metabolites in immune cell development and differentiation,the mechanisms linking microbiota absence to systemic immune deficits remain incompletely defined.Here,droplet-based single-cell RNA sequencing of bone marrow and peripheral blood from both germ-free and specific pathogen-free mice was performed,identifying 25 transcriptionally distinct cell types.Neutrophil apoptosis was elevated in germ-free mice,potentially due to the absence of niacin dehydrogenase,a metabolite primarily produced by Pseudomonas.In addition,germ-free mice exhibited increased excretion of 5’-methylthioadenosine,enhanced ERK activation driven by reactive oxygen species,and disruption of bone marrow stromal antigen 2 signaling.Monocytes and CD8^(+)T cells from germ-free mice showed diminished responses to interferon-β and interferon-γ,consistent with heightened viral susceptibility.These findings establish a microbiota-dependent regulatory pathway linking immunodeficiency to microbial absence in germ-free mice,confirmed through complementary validation techniques.
文摘The tumor microenvironment(TME)is characterized by a symbiosis between cancer cells and the immune cells.The scarcity of oxygen generates hostility that forces cancer cells to alter their biological features in solid tumors.In response to low oxygen availability,the Hypoxia Inducible Factors(HIF-1/2/3α)act as metabolic mediators,producing extracellular metabolites in the tumor microenvironment that influence the immune cells.The modulation of lactate and adenosine on immune evasion has been widely described;however,under hypoxic conditions,it has been barely addressed.Evidence has demonstrated an interplay between cancer and the immune cells,and the present review explores thefindings that support HIFs bridging the gap between the rise of these metabolites and the immunosurveillance failure in a hypoxic context.Moreover,new insights based on systemic oxygen administration are discussed,which might counterbalance the effect mediated by lactate and adenosine,to recover anti-tumor immunity.Thus,the disruption of anti-tumor immunity has been the focus of recent research and this novel avenue opens therapeutic vulnerabilities that can be useful for cancer patients.
基金funded by the Spanish Ministry of Economy and Competitiveness,No.PID(2019)-106498GB-100 (to MVS)by the Instituto de Salud CarlosⅢ,Fondo Europeo de Desarrollo Regional"Una manera de hacer Europa",No.PI19/00071 (to MAB)+2 种基金the RETICS subprograms of Spanish Networks OftoRed,Nos.RD16/0008/0026 (to DGB) and RD16/0008/0016 (to DGB)RICORS Terav,No.RD16/0011/0001 (to DGB)from Instituto de Salud CarlosⅢby the Fundacion Seneca,Agencia de Cienciay Tecnologia Región de Murcia,No.19881/GERM/15 (all to MVS)
文摘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.
文摘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.
基金funded by Science and Technology Project of Haihe Laboratory of Modern Chinese Medicine(24HHZYSS00002)the National Key Research and Development Program of China(2022YFC3501800)the National Natural Science Foundation of China(82204878).
文摘Recent research has highlighted the potential of Codonopsis Radix to modulate the immune system,making it a promising candidate for treating chronic inflammatory and cardiovascular diseases,tumors,and aging.However,because of the complex immune activities of its various components,a comprehensive understanding of Codonopsis Radix immune-regulating properties is still lacking.This knowledge gap hinders its widespread utilization in clinical practice.Therefore,this review aimed to assess the impact of Codonopsis Radix on the immune system and elucidate its underlying mechanisms.Additionally,we compared the immunomodulatory effects of different active ingredients derived from Codonopsis Radix to provide a theoretical basis for future investigations on immunomodulation.
基金CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-035National Key Research and Development Project,Grant/Award Number:2022YFA1103803。
文摘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.
文摘Smoking has a complex impact on the immune system, affecting both innate and adaptive immunity. It can exacerbate pathogenic immune responses and attenuate defensive immunity, leading to a higher susceptibility to infections and certain diseases. The chemicals in cigarette smoke, such as nicotine and carbon monoxide, can alter immune cell functions and inflammatory responses. Smoking can also have long-term effects on the immune system, with some changes persisting even after quitting [1]. According to a Penn Medicine Physician, the Medical Oncologist Dr. David Porter, “People who are smokers tend to get sicker from infections”, “It may be that smoking impacts the immune system’s ability to respond appropriately”. Thus, such individuals within smoking exposure history might be considered as immunocompromised due to the altered and weakened immune system. Cigarette smoking is a prevalent habit with far-reaching health implications. Among its many adverse effects, smoking significantly alters the immune system’s functionality [1].
文摘The immune system operates as a complex organization with distinct roles and functions. Excitingly we recognized the similarities between the cellular dynamics of the immune system and our lives, activities, and behaviors. Observing the immune system can guide how to respond to various daily situations, including when to react, tolerate, or ignore. Recognizing this analogy between our lives and the immune system should motivate us to adopt a wisdom-based approach when investigating the mechanisms and future discoveries related to this system and to deepen our understanding of this complex system with newfound respect. In this context, the present review examines several integral biological processes of the immune system by drawing parallels between them and human life, activities, and behaviors to learn how we must behave based on the insights offered by this complex organization. The literature search was conducted in international databases such as PubMed/MEDLINE and Google Scholar search engine using English equivalent keywords from 1998 up to April 2023. The search strategy used the following subject heading terms: Immune system, analogy, human life, cellular dynamics, memory, tolerance, and ignorance. In conclusion, the immune system is a complex organization comprising various cells interacting within specific sites and networks, communicating, drawing experiences, and learning how to tolerate certain conditions that make it share certain similarities with human life.
基金supported by the“Pioneer”and“Leading Goose”R&D Program of Zhejiang(No.2022C04014)Zhejiang Science and Technology Major Program on Agricultural New Variety Breeding(No.2021C02068-10).
文摘Birds,a fascinating and diverse group occupying various habitats worldwide,exhibit a wide range of life-history traits,reproductive methods,and migratory behaviors,all of which influence their immune systems.The association between major histocompatibility complex(MHC)genes and certain ecological factors in response to pathogen selection has been extensively studied;however,the role of the co-working molecule T cell receptor(TCR)remains poorly understood.This study aimed to analyze the copy numbers of TCR-V genes,the selection pressure(ωvalue)on MHC genes using available genomic data,and their potential ecological correlates across 93 species from 13 orders.The study was conducted using the publicly available genome data of birds.Our findings suggested that phylogeny influences the variability in TCR-V gene copy numbers and MHC selection pressure.The phylogenetic generalized least squares regression model revealed that TCR-Vαδcopy number and MHC-I selection pressure were positively associated with body mass.Clutch size was correlated with MHC selection pressure,and Migration was correlated with TCR-Vβcopy number.Further analyses revealed that the TCR-Vβcopy number was positively correlated with MHC-IIB selection pressure,while the TCR-Vγcopy number was negatively correlated with MHC-I peptide-binding region selection pressure.Our findings suggest that TCR-V diversity is significant in adaptive evolution and is related to species’life-history strategies and immunological defenses and provide valuable insights into the mechanisms underlying TCR-V gene duplication and MHC selection in avian species.
文摘In this paper,different kinds of enzymes,immune factors and regulatory factors of the immune system of crustaceans are summarized and then combed systematically and thoroughly. According to the mutual influence and effects of these factors,different symbolic forms are introduced to express the effects,and ultimately the whole node graph of the system is obtained. The graph theory can be used for further researches on the immune system of crustacean.
基金supported by the National Institute of Perinatology,Mexico City(234560)FONSEC SSA/IMSS/ISSSTE 2015-1(261435)
文摘Major depression during pregnancy is a common psychiatric disorder that arises from a complex and mul- tifactorial etiology. Psychosocial stress, sex, hormones, and genetic vulnerability increase the risk for triggering mood disorders. Microglia and toll-like receptor 4 play a crucial role in triggering wide and varied stress-induced responses mediated through activation of the inflammasome; this leads to the secretion of inflammatory cytokines, increased serotonin metabolism, and reduction of neurotransmitter availability along with hypothalamic-pituitary-adrenal axis hyperactivity. Dysregulation of this intricate neu- roimmune communication network during pregnancy modifies the maternal milieu, enhancing the emergence of depressive symptoms and negative obstetric and neu- ropsychiatric outcomes. Although several studies have clearly demonstrated the role of the innate immune system in major depression, it is still unclear how the placenta, the brain, and the monoaminergic and neuroendocrine systems interact during perinatal depression. Thus, in the present review we describe the cellular and molecular interactions between these systems in major depression during preg- nancy, proposing that the same stress-related mechanisms involved in the activation of the NLRP3 inflammasome in microglia and peripheral myeloid cells in depressed patients operate in a similar fashion in the neuroimmune placenta during perinatal depression. Thus, activation of Toll-like receptor 2 and 4 signaling and the NLRP3 inflammasome in placental immune cells may promote a shift of the Thl/Th2 bias towards a predominant Thl/Thl7 inflammatory response, associated with increased secretion of pro-inflammatory cytokines, among other secreted autocrine and paracrine mediators, which play a crucial role in triggering and/or exacerbating depressive symptoms during pregnancy.
文摘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.
基金Supported by The National Institute of Health(NIH/NCI R01CA140290-3 to Murray NR)
文摘The immune system plays a complex role in the development and progression of pancreatic cancer. Inflammation can promote the formation of premalignant lesions and accelerate pancreatic cancer development. Conversely, pancreatic cancer is characterized by an immunosuppressive environment, which is thought to promote tumor progression and invasion. Here we review the current literature describing the role of the immune response in the progressive development of pancreatic cancer, with a focus on the mechanisms that drive recruitment and activation of immune cells at the tumor site, and our current understanding of the function of the immune cell types at the tumor. Recent clinical and preclinical data are reviewed, detailing the involvement of the immune response in pancreatitis and pancreatic cancer, including the role of specific cytokines and implications for disease outcome. Acute pancreatitis is characterized by a predominantly innate immune response, while chronic pancreatitis elicits an immune response that involves both innate and adaptive immune cells, and often results in profound sys-temic immune-suppression. Pancreatic adenocarcinoma is characterized by marked immune dysfunction driven by immunosuppressive cell types, tumor-promoting immune cells, and defective or absent inflammatory cells. Recent studies reveal that immune cells interact with cancer stem cells and tumor stromal cells, and these interactions have an impact on development and progression of pancreatic ductal adenocarcinoma(PDAC). Finally, current PDAC therapies are reviewed and the potential for harnessing the actions of the immune response to assist in targeting pancreatic cancer using immunotherapy is discussed.
基金supported by the Intramural Research Program of the National Institutes of HealthNational Institute of Dental and Craniofacial Research, USA+1 种基金supported by grant 2012DFA31370 from the International S&T Cooperation Program of Chinathe National Nature Science Foundation of China (81321002)
文摘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.
文摘Nutrition during perinatal period is more critical for the developme nt of the immune system than during adulthood, and the relationship between earl y nutrition and diseases in later life has been established. In humans and labor atory animals, the plasticity of metabolic function in foetuses or neonates enab les them to adapt to malnutrition for survival; however, such an adaptation, as usually evidenced by retarded growth, stunted development of lymphoid organs and impaired immunocompetence, can maintain and persist into later life even when n utrition is improved. Early nutrition may thus programme' the immune system of a nimals. Limited experimental studies have also revealed that long-term immunity against nematode parasites in sheep can be enhanced by a short-term protein su pplementation shortly after weaning, a form of 'nutritional programming', but su ch an effect appears to vanish if the nutritional status of young animals alread y meets at least the requirement for maintenance.
基金This work was supported by the Natural Science Foundation of Shandong Province(No.Y2005G12)National Natural ScienceFoundation of China(No.60674062)and the Information Industry Foundation of Shandong Province(No.2006R00046).
文摘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.
