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Reviews in Endocrine & Metabolic... Dec 2020In light of the most challenging public health crisis of modern history, COVID-19 mortality continues to rise at an alarming rate. Patients with co-morbidities such as... (Review)
Review
In light of the most challenging public health crisis of modern history, COVID-19 mortality continues to rise at an alarming rate. Patients with co-morbidities such as hypertension, cardiovascular disease, and diabetes mellitus (DM) seem to be more prone to severe symptoms and appear to have a higher mortality rate. In this review, we elucidate suggested mechanisms underlying the increased susceptibility of patients with diabetes to infection with SARS-CoV-2 with a more severe COVID-19 disease. The worsened prognosis of COVID-19 patients with DM can be attributed to a facilitated viral uptake assisted by the host's receptor angiotensin-converting enzyme 2 (ACE2). It can also be associated with a higher basal level of pro-inflammatory cytokines present in patients with diabetes, which enables a hyperinflammatory "cytokine storm" in response to the virus. This review also suggests a link between elevated levels of IL-6 and AMPK/mTOR signaling pathway and their role in exacerbating diabetes-induced complications and insulin resistance. If further studied, these findings could help identify novel therapeutic intervention strategies for patients with diabetes comorbid with COVID-19.
Topics: COVID-19; Comorbidity; Coronavirus Infections; Diabetes Mellitus; Disease Susceptibility; Humans; Pandemics; Pneumonia, Viral
PubMed: 32743793
DOI: 10.1007/s11154-020-09573-6 -
Toxicology and Applied Pharmacology May 2016Rapid advances and applications in nanotechnology are expected to result in increasing occupational exposure to nano-sized materials whose health impacts are still not... (Review)
Review
Rapid advances and applications in nanotechnology are expected to result in increasing occupational exposure to nano-sized materials whose health impacts are still not completely understood. Scientific efforts are required to identify hazards from nanomaterials and define risks and precautionary management strategies for exposed workers. In this scenario, the definition of susceptible populations, which may be at increased risk of adverse effects may be important for risk assessment and management. The aim of this review is to critically examine available literature to provide a comprehensive overview on susceptibility aspects potentially affecting heterogeneous responses to nanomaterials workplace exposure. Genetic, genotoxic and epigenetic alterations induced by nanomaterials in experimental studies were assessed with respect to their possible function as determinants of susceptibility. Additionally, the role of host factors, i.e. age, gender, and pathological conditions, potentially affecting nanomaterial toxicokinetic and health impacts, were also analysed. Overall, this review provides useful information to obtain insights into the nanomaterial mode of action in order to identify potentially sensitive, specific susceptibility biomarkers to be validated in occupational settings and addressed in risk assessment processes. The findings of this review are also important to guide future research into a deeper characterization of nanomaterial susceptibility in order to define adequate risk communication strategies. Ultimately, identification and use of susceptibility factors in workplace settings has both scientific and ethical issues that need addressing.
Topics: Animals; Biomarkers; Disease Susceptibility; Genetic Variation; Humans; Inhalation Exposure; Metabolic Networks and Pathways; Nanostructures; Occupational Exposure
PubMed: 26724381
DOI: 10.1016/j.taap.2015.12.018 -
European Journal of Immunology Apr 2019Systemic lupus erythematosus (SLE) is a complex autoimmune disease, in which immune defects can occur at multiple points of the cascading auto-aggressive immune... (Review)
Review
Systemic lupus erythematosus (SLE) is a complex autoimmune disease, in which immune defects can occur at multiple points of the cascading auto-aggressive immune reactions, resulting in a striking heterogeneity of clinical presentations. The clinical manifestations of such autoimmune response can be severe: common manifestations symptoms include rash and renal inflammation progressing to kidney failure. Autophagy, the cellular "self-digestion" process, is a key factor in the interplay between innate and adaptive immunity. Dysregulation of autophagy has been implicated in numerous autoimmune diseases. Several lines of evidence from genomic studies, cell culture systems, animal models, and human patients are emerging to support the role of autophagy in progression and pathogenesis of SLE. In this review, we summarize recent key findings on the aberrations of autophagy in SLE, with a special focus on how deregulated autophagy promotes autoimmunity and renal damage. We will also discuss how the observed findings may be translated into therapeutic settings.
Topics: Adaptive Immunity; Alleles; Animals; Autoimmunity; Autophagy; Biomarkers; Disease Susceptibility; Environment; Genetic Predisposition to Disease; Humans; Immunity, Innate; Lupus Erythematosus, Systemic; Polymorphism, Single Nucleotide
PubMed: 30776086
DOI: 10.1002/eji.201847679 -
Annales de Biologie Clinique Jun 2017Preeclampsia which affects approximatively 2% of pregnancies is a major cause of maternal and perinatal morbidity and mortality. Pathogenesis of pre-eclampsia is... (Review)
Review
Preeclampsia which affects approximatively 2% of pregnancies is a major cause of maternal and perinatal morbidity and mortality. Pathogenesis of pre-eclampsia is nowadays increasingly understood. It implies multiple actors and biomarkers appear to be playing a major role. New uses of those biomarkers for risk stratification and diagnosis of predisposed preeclamptic patients followed by obstetricians is an hot topic. The combined approach of biomarkers, medical history and obstetrical ultrasounds enables risk estimation in the first quarter and later on. A better understanding of this risk would enable better monitoring of obstetrical patients and reduce the occurrence of adverse complications for them and for the fetal well-being.
Topics: Biomarkers; Disease Susceptibility; Female; Humans; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Prognosis; Risk Factors
PubMed: 28540849
DOI: 10.1684/abc.2017.1240 -
Current Opinion in Immunology Oct 2019It is now well established that the exposure to certain environments such as farms has the potential to protect from the development of allergies later in life. This... (Review)
Review
It is now well established that the exposure to certain environments such as farms has the potential to protect from the development of allergies later in life. This protection is achieved when repeated exposure to the farming environment occurs early in life, but persists when children spend sufficient amount of time in contact with livestock and hay, and drink unpasteurized milk. The capacity of farm dust to protect from allergy development lies, amongst others, in the microbe composition in the farm. These protective microbes release various metabolites and cell wall components that change farmers' home dust composition, when compared to urbanized home dust. Additionally, they can colonize various barrier sites (skin, lung, intestine) in farmers' children, leading to persistent changes in the way their immune system and their barrier cells respond to environmental allergens.
Topics: Agriculture; Animals; Disease Susceptibility; Environmental Exposure; Gene-Environment Interaction; Genetic Predisposition to Disease; Humans; Hypersensitivity, Immediate; Microbiota
PubMed: 31499321
DOI: 10.1016/j.coi.2019.08.001 -
Seminars in Immunopathology Mar 2019Sex differences in immunity are well described in the literature and thought to be mainly driven by sex hormones and sex-linked immune response genes. The... (Review)
Review
Sex differences in immunity are well described in the literature and thought to be mainly driven by sex hormones and sex-linked immune response genes. The gastrointestinal tract (GIT) is one of the largest immune organs in the body and contains multiple immune cells in the GIT-associated lymphoid tissue, Peyer's patches and elsewhere, which together have profound effects on local and systemic inflammation. The GIT is colonised with microbial communities composed of bacteria, fungi and viruses, collectively known as the GIT microbiota. The GIT microbiota drives multiple interactions locally with immune cells that regulate the homeostatic environment and systemically in diverse tissues. It is becoming evident that the microbiota differs between the sexes, both in animal models and in humans, and these sex differences often lead to sex-dependent changes in local GIT inflammation, systemic immunity and susceptibility to a range of inflammatory diseases. The sexually dimorphic microbiome has been termed the 'microgenderome'. Herein, we review the evidence for the microgenderome and contemplate the role it plays in driving sex differences in immunity and disease susceptibility. We further consider the impact that biological sex might play in the response to treatments aimed at manipulating the GIT microbiota, such as prebiotics, live biotherapeutics, (probiotics, synbiotics and bacteriotherapies) and faecal microbial transplant. These alternative therapies hold potential in the treatment of both psychological (e.g., anxiety, depression) and physiological (e.g., irritable bowel disease) disorders differentially affecting males and females.
Topics: Animals; Disease Susceptibility; Female; Gastrointestinal Microbiome; Gastrointestinal Tract; Gonadal Steroid Hormones; Humans; Male; Peyer's Patches; Sex Characteristics
PubMed: 30298433
DOI: 10.1007/s00281-018-0716-7 -
Journal of Autoimmunity Feb 2016Autism spectrum disorders (ASD) are complex neurodevelopmental conditions that have been rising markedly in prevalence for the past 30 years, now thought to affect 1 in... (Review)
Review
Autism spectrum disorders (ASD) are complex neurodevelopmental conditions that have been rising markedly in prevalence for the past 30 years, now thought to affect 1 in 68 in the United States. This has prompted the search for possible explanations, and has even resulted in some controversy regarding the "true" prevalence of autism. ASD are influenced by a variety of genetic, environmental, and possibly immunological factors that act during critical periods to alter key developmental processes. This can affect multiple systems and manifests as the social and behavioral deficits that define these disorders. The interaction of environmental exposures in the context of an individual's genetic susceptibilities manifests differently in each case, leading to heterogeneous phenotypes and varied comorbid symptoms within the disorder. This has also made it very difficult to elucidate underlying genes and exposure profiles, but progress is being made in this area. Some pharmaceutical drugs, toxicants, and metabolic and nutritional factors have been identified in epidemiological studies as increasing autism risk, especially during the prenatal period. Immunologic risk factors, including maternal infection during pregnancy, autoantibodies to fetal brain proteins, and familial autoimmune disease, have consistently been observed across multiple studies, as have immune abnormalities in individuals with ASD. Mechanistic research using animal models and patient-derived stem cells will help researchers to understand the complex etiology of these neurodevelopmental disorders, which will lead to more effective therapies and preventative strategies. Proposed therapies that need more investigation include special diets, probiotics, immune modulation, oxytocin, and personalized pharmacogenomic targets. The ongoing search for biomarkers and better treatments will result in earlier identification of ASD and provide much needed help and relief for afflicted families.
Topics: Animals; Autism Spectrum Disorder; Autoimmunity; Brain; Disease Susceptibility; Environment; Gene-Environment Interaction; Genetic Predisposition to Disease; Humans; Prevalence; Risk Factors
PubMed: 26725748
DOI: 10.1016/j.jaut.2015.11.003 -
British Journal of Anaesthesia Jul 2023Most patients with malignant hyperthermia susceptibility diagnosed by the in vitro caffeine-halothane contracture test (CHCT) develop excessive force in response to...
BACKGROUND
Most patients with malignant hyperthermia susceptibility diagnosed by the in vitro caffeine-halothane contracture test (CHCT) develop excessive force in response to halothane but not caffeine (halothane-hypersensitive). Hallmarks of halothane-hypersensitive patients include high incidence of musculoskeletal symptoms at rest and abnormal calcium events in muscle. By measuring sensitivity to halothane of myotubes and extending clinical observations and cell-level studies to a large group of patients, we reach new insights into the pathological mechanism of malignant hyperthermia susceptibility.
METHODS
Patients with malignant hyperthermia susceptibility were classified into subgroups HH and HS (positive to halothane only and positive to both caffeine and halothane). The effects on [Ca] of halothane concentrations between 0.5 and 3 % were measured in myotubes and compared with CHCT responses of muscle. A clinical index that summarises patient symptoms was determined for 67 patients, together with a calcium index summarising resting [Ca] and spontaneous and electrically evoked Ca events in their primary myotubes.
RESULTS
Halothane-hypersensitive myotubes showed a higher response to halothane 0.5% than the caffeine-halothane hypersensitive myotubes (P<0.001), but a lower response to higher concentrations, comparable with that used in the CHCT (P=0.055). The HH group had a higher calcium index (P<0.001), but their clinical index was not significantly elevated vs the HS. Principal component analysis identified electrically evoked Ca spikes and resting [Ca] as the strongest variables for separation of subgroups.
CONCLUSIONS
Enhanced sensitivity to depolarisation and to halothane appear to be the primary, mutually reinforcing and phenotype-defining defects of halothane-hypersensitive patients with malignant hyperthermia susceptibility.
Topics: Humans; Malignant Hyperthermia; Halothane; Calcium; Muscle Fibers, Skeletal; Disease Susceptibility; Caffeine; Muscle Contraction
PubMed: 36792386
DOI: 10.1016/j.bja.2023.01.008 -
Journal of the Academy of Nutrition and... Apr 2018
Topics: DNA Glycosylases; Diet, Mediterranean; Disease Susceptibility; Genetic Predisposition to Disease; Humans; Risk Factors
PubMed: 29305132
DOI: 10.1016/j.jand.2017.09.026 -
Journal of Magnetic Resonance (San... Jul 2018The ultimate goal of MRI is to provide information on biological tissue microstructure and function. Quantitative Susceptibility Mapping (QSM) is one of the newer... (Review)
Review
The ultimate goal of MRI is to provide information on biological tissue microstructure and function. Quantitative Susceptibility Mapping (QSM) is one of the newer approaches for studying tissue microstructure by means of measuring phase of Gradient Recalled Echo (GRE) MRI signal. The fundamental question in the heart of this approach is: what is the relationship between the net phase/frequency of the GRE signal from an imaging voxel and the underlying tissue microstructure at the cellular and sub-cellular levels? In the presence of external magnetic field, biological media (e.g. cells, cellular components, blood) become magnetized leading to the MR signal frequency shift that is affected not only by bulk magnetic susceptibility but by the local cellular environment as well. The latter effect is often termed the Lorentzian contribution to the frequency shift. Evaluating the Lorentzian contribution - one of the most intriguing and challenging problems in this field - is the main focus of this review. While the traditional approach to this problem is based on introduction of an imaginary Lorentzian cavity, a more rigorous treatment was proposed recently based on a statistical approach and a direct solution of the Maxwell equations. This approach, termed the Generalized Lorentzian Tensor Approach (GLTA), is especially fruitful for describing anisotropic biological media. The GLTA adequately accounts for two types of anisotropy: anisotropy of magnetic susceptibility and tissue structural anisotropy (e.g., cylindrical axonal bundles in white matter). In the framework of the GLTA the frequency shift due to the local environment is described in terms of the Lorentzian tensor L̂ which can have a substantially different structure than the susceptibility tensor χ̂. While the components of χ̂ are compartmental susceptibilities "weighted" by their volume fractions, the components of L̂ are additionally weighted by specific numerical factors depending on cellular geometrical symmetry. In addition to describing the GLTA that is a phenomenological approach largely based on considering the system symmetry, we also briefly discuss a microscopic approaches to the problem that are based on modeling of the MR signal in different regimes (i.e. static dephasing vs. motion narrowing) and in different cellular environments (e.g., accounting for WM microstructure).
Topics: Algorithms; Animals; Anisotropy; Disease Susceptibility; Heart; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging
PubMed: 29730126
DOI: 10.1016/j.jmr.2018.04.014