-
Blood Oct 2020Clonal expansions of mutated hematopoietic cells, termed clonal hematopoiesis, are common in aging humans. One expected consequence of mutation-associated clonal... (Review)
Review
Clonal expansions of mutated hematopoietic cells, termed clonal hematopoiesis, are common in aging humans. One expected consequence of mutation-associated clonal hematopoiesis is an increased risk of hematologic cancers, which has now been shown in several studies. However, the hematopoietic stem cells that acquire these somatic mutations also give rise to mutated immune effector cells, such as monocytes, granulocytes, and lymphocytes. These effector cells can potentially influence many disease states, especially those with a chronic inflammatory component. Indeed, several studies have now shown that clonal hematopoiesis associates with increased risk of atherosclerotic cardiovascular disease. Emerging data also associate clonal hematopoiesis with other nonhematologic diseases. Here, we will review recent studies linking clonal hematopoiesis to altered immune function, inflammation, and nonmalignant diseases of aging.
Topics: Animals; Biomarkers; Cardiovascular Diseases; Clonal Evolution; Clonal Hematopoiesis; Disease Susceptibility; Genetic Association Studies; Genetic Predisposition to Disease; Hematopoiesis; Humans; Mutation; Organ Specificity; Phenotype; Terminology as Topic
PubMed: 32736379
DOI: 10.1182/blood.2019000989 -
Journal of Experimental & Clinical... Aug 2021Tumor resistance to apoptosis and the immunosuppressive tumor microenvironment are two major contributors to poor therapeutic responses during cancer intervention.... (Review)
Review
Tumor resistance to apoptosis and the immunosuppressive tumor microenvironment are two major contributors to poor therapeutic responses during cancer intervention. Pyroptosis, a lytic and inflammatory programmed cell death pathway distinct from apoptosis, has subsequently sparked notable interest among cancer researchers for its potential to be clinically harnessed and to address these problems. Recent evidence indicates that pyroptosis induction in tumor cells leads to a robust inflammatory response and marked tumor regression. Underlying its antitumor effect, pyroptosis is mediated by pore-forming gasdermin proteins that facilitate immune cell activation and infiltration through their release of pro-inflammatory cytokines and immunogenic material following cell rupture. Considering its inflammatory nature, however, aberrant pyroptosis may also be implicated in the formation of a tumor supportive microenvironment, as evidenced by the upregulation of gasdermin proteins in certain cancers. In this review, the molecular pathways leading to pyroptosis are introduced, followed by an overview of the seemingly entangled links between pyroptosis and cancer. We describe what is known regarding the impact of pyroptosis on anticancer immunity and give insight into the potential of harnessing pyroptosis as a tool and applying it to novel or existing anticancer strategies.
Topics: Animals; Biomarkers; Combined Modality Therapy; Disease Management; Disease Susceptibility; Gene Expression Regulation, Neoplastic; Humans; Immunity; Neoplasms; Pyroptosis; Signal Transduction; Treatment Outcome
PubMed: 34429144
DOI: 10.1186/s13046-021-02065-8 -
Communications Biology Nov 2021Modern societies are experiencing an increasing trend of reduced sleep duration, with nocturnal sleeping time below the recommended ranges for health. Epidemiological... (Review)
Review
Modern societies are experiencing an increasing trend of reduced sleep duration, with nocturnal sleeping time below the recommended ranges for health. Epidemiological and laboratory studies have demonstrated detrimental effects of sleep deprivation on health. Sleep exerts an immune-supportive function, promoting host defense against infection and inflammatory insults. Sleep deprivation has been associated with alterations of innate and adaptive immune parameters, leading to a chronic inflammatory state and an increased risk for infectious/inflammatory pathologies, including cardiometabolic, neoplastic, autoimmune and neurodegenerative diseases. Here, we review recent advancements on the immune responses to sleep deprivation as evidenced by experimental and epidemiological studies, the pathophysiology, and the role for the sleep deprivation-induced immune changes in increasing the risk for chronic diseases. Gaps in knowledge and methodological pitfalls still remain. Further understanding of the causal relationship between sleep deprivation and immune deregulation would help to identify individuals at risk for disease and to prevent adverse health outcomes.
Topics: Disease Susceptibility; Humans; Immunity; Inflammation; Sleep Deprivation
PubMed: 34795404
DOI: 10.1038/s42003-021-02825-4 -
Relationship Between the ABO Blood Group and the Coronavirus Disease 2019 (COVID-19) Susceptibility.Clinical Infectious Diseases : An... Jul 2021To explore any relationship between the ABO blood group and the coronavirus disease 2019 (COVID-19) susceptibility, we compared ABO blood group distributions in 2173...
To explore any relationship between the ABO blood group and the coronavirus disease 2019 (COVID-19) susceptibility, we compared ABO blood group distributions in 2173 COVID-19 patients with local control populations, and found that blood group A was associated with an increased risk of infection, whereas group O was associated with a decreased risk.
Topics: ABO Blood-Group System; COVID-19; Disease Susceptibility; Humans; Retrospective Studies; SARS-CoV-2
PubMed: 32750119
DOI: 10.1093/cid/ciaa1150 -
Nature Immunology Jun 2020Impressive progress has been made over the last several years toward understanding how almost every aspect of the immune system contributes to the expression of systemic... (Review)
Review
Impressive progress has been made over the last several years toward understanding how almost every aspect of the immune system contributes to the expression of systemic autoimmunity. In parallel, studies have shed light on the mechanisms that contribute to organ inflammation and damage. New approaches that address the complicated interaction between genetic variants, epigenetic processes, sex and the environment promise to enlighten the multitude of pathways that lead to what is clinically defined as systemic lupus erythematosus. It is expected that each patient owns a unique 'interactome', which will dictate specific treatment.
Topics: Animals; Autoimmunity; Diagnosis, Differential; Disease Susceptibility; Environmental Exposure; Genetic Predisposition to Disease; Genetic Variation; Humans; Immunity, Innate; Lupus Erythematosus, Systemic; Lymphocyte Subsets; Organ Specificity; Sex Factors
PubMed: 32367037
DOI: 10.1038/s41590-020-0677-6 -
Journal of Clinical Immunology Oct 2019Regulatory T (Treg) cells expressing the transcription factor forkhead box P3 (Foxp3) play a requisite role in the maintenance of immunological homeostasis and... (Review)
Review
Regulatory T (Treg) cells expressing the transcription factor forkhead box P3 (Foxp3) play a requisite role in the maintenance of immunological homeostasis and prevention of peripheral self-tolerance breakdown. Although Foxp3 by itself is neither necessary nor sufficient to specify many aspects of the Treg cell phenotype, its sustained expression in Treg cells is indispensable for their phenotypic stability, metabolic fitness, and regulatory function. In this review, we summarize recent advances in Treg cell biology, with a particular emphasis on the role of Foxp3 as a transcriptional modulator and metabolic gatekeeper essential to an effective immune regulatory response. We discuss these findings in the context of human inborn errors of immune dysregulation, with a focus on FOXP3 mutations, leading to Treg cell deficiency. We also highlight emerging concepts of therapeutic Treg cell reprogramming to restore tolerance in the settings of immune dysregulatory disorders.
Topics: Animals; Biomarkers; Cell Communication; Cell Differentiation; Cellular Reprogramming; Disease Susceptibility; Energy Metabolism; Forkhead Transcription Factors; Gene Expression Regulation; Humans; Immune Tolerance; Immunomodulation; Immunotherapy; Organ Specificity; Phenotype; T-Lymphocyte Subsets; T-Lymphocytes, Regulatory
PubMed: 31478130
DOI: 10.1007/s10875-019-00684-7 -
Journal of Cancer Research and... 2016Oral cancer is the sixth most common malignancy in the world. Oral cancer is of major concern in Southeast Asia primarily because of the prevalent oral habits of betel... (Review)
Review
Oral cancer is the sixth most common malignancy in the world. Oral cancer is of major concern in Southeast Asia primarily because of the prevalent oral habits of betel quid chewing, smoking, and alcohol consumption. Despite recent advances in cancer diagnoses and therapies, the 5.year survival rate of oral cancer patients has remained at a dismal 50% in the last few decades. This paper is an overview of the various etiological agents and risk factors implicated in the development of oral cancer.
Topics: Animals; Cell Transformation, Neoplastic; Disease Susceptibility; Environment; Epigenesis, Genetic; Genetic Predisposition to Disease; Humans; Immunocompromised Host; Mouth Neoplasms; Risk Factors; Smoking
PubMed: 27461593
DOI: 10.4103/0973-1482.186696 -
Neuropharmacology Mar 2021Addiction is a chronic brain disease that has dramatic health and socioeconomic consequences worldwide. Multiple approaches have been used for decades to clarify the... (Review)
Review
Addiction is a chronic brain disease that has dramatic health and socioeconomic consequences worldwide. Multiple approaches have been used for decades to clarify the neurobiological basis of this disease and to identify novel potential treatments. This review summarizes the main brain networks involved in the vulnerability to addiction and specific innovative technological approaches to investigate these neural circuits. First, the evolution of the definition of addiction across the Diagnostic and Statistical Manual of Mental Disorders (DSM) is revised. We next discuss several innovative experimental techniques that, combined with behavioral approaches, have allowed recent critical advances in understanding the neural circuits involved in addiction, including DREADDs, calcium imaging, and electrophysiology. All these techniques have been used to investigate specific neural circuits involved in vulnerability to addiction and have been extremely useful to clarify the neurobiological basis of each specific component of the addictive process. These novel tools targeting specific brain regions are of great interest to further understand the different aspects of this complex disease. This article is part of the special issue on 'Vulnerabilities to Substance Abuse.'.
Topics: Animals; Behavior, Addictive; Brain; Calcium Signaling; Disease Susceptibility; Electroencephalography; Electrophysiological Phenomena; Humans; Illicit Drugs; Nerve Net; Piperazines
PubMed: 33482225
DOI: 10.1016/j.neuropharm.2021.108466 -
British Journal of Haematology Jan 2022Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by complement-mediated intravascular haemolysis, severe thrombophilia and bone marrow failure. While for... (Review)
Review
Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by complement-mediated intravascular haemolysis, severe thrombophilia and bone marrow failure. While for patients with bone marrow failure the treatment follows that of immune-mediated aplastic anaemia, that of classic, haemolytic PNH is based on anti-complement medication. The anti-C5 monoclonal antibody eculizumab has revolutionized treatment, resulting in control of intravascular haemolysis and thromboembolic risk, with improved long-term survival. Novel strategies of complement inhibition are emerging. New anti-C5 agents reproduce the safety and efficacy of eculizumab, with improved patient convenience. Proximal complement inhibitors have been developed to address C3-mediated extra-vascular haemolysis and seem to improve haematological response.
Topics: Algorithms; Clinical Decision-Making; Combined Modality Therapy; Disease Management; Disease Susceptibility; Genetic Predisposition to Disease; Hemoglobinuria, Paroxysmal; Humans; Phenotype; Prognosis; Standard of Care; Treatment Outcome
PubMed: 34355382
DOI: 10.1111/bjh.17753 -
Genes Oct 2019The poultry industry currently accounts for the production of around 118 million metric tons of meat and around 74 million metric tons of eggs annually. As the global...
The poultry industry currently accounts for the production of around 118 million metric tons of meat and around 74 million metric tons of eggs annually. As the global population continues to increase, so does our reliance on poultry as a food source. It is therefore of vital importance that we safeguard this valuable resource and make the industry as economically competitive as possible. Avian viral infections, however, continue to cost the poultry industry billions of dollars annually. This can be in terms of vaccination costs, loss of birds and decreased production. With a view to improving the health and welfare of commercial birds and to minimizing associated economic losses, it is therefore of great importance that we try to understand the genetic mechanisms underlying host susceptibility and resilience to some of the major viral pathogens that threaten the poultry species. Some avian viruses, through their zoonotic potential, also pose a risk to human health. This Special Issue will present papers that describe our current knowledge on host responses to various viral pathogens, the genetics underlying those responses and how genomics can begin to provide a solution for resolving the threat posed by these infections.
Topics: Animals; Birds; Disease Susceptibility; Genetic Predisposition to Disease; Genomics; Influenza in Birds; Poultry; Poultry Diseases; Vaccination
PubMed: 31618995
DOI: 10.3390/genes10100814