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Frontiers in Immunology 2020
Topics: Age Factors; Disease Susceptibility; Humans; Immune System Diseases
PubMed: 33013866
DOI: 10.3389/fimmu.2020.02050 -
The Journals of Gerontology. Series B,... Feb 2020Personality, especially the dimensions of neuroticism and conscientiousness, has prospectively predicted the risk of incident Alzheimer's disease (AD). Such a... (Review)
Review
Personality, especially the dimensions of neuroticism and conscientiousness, has prospectively predicted the risk of incident Alzheimer's disease (AD). Such a relationship could be explained by personality and AD risk having a common cause such as a gene; by personality creating a predisposition for AD through health behavior or inflammation; by personality exerting a pathoplastic effect on the cognitive consequences of neuropathology; or by AD and personality change existing on a disease spectrum that begins up to decades before diagnosis. Using the 5-dimensional taxonomy of personality, the present review describes how these models might arise, the evidence for each, and how they might be distinguished from one another empirically. At present, the evidence is sparse but tends to suggest predisposition and/or pathoplastic relationships. Future studies using noninvasive assessment of neuropathology are needed to distinguish these 2 possibilities.
Topics: Aged; Alzheimer Disease; Disease Susceptibility; Genetic Predisposition to Disease; Humans; Personality
PubMed: 29846724
DOI: 10.1093/geronb/gby063 -
International Journal of Molecular... Sep 2021Thalassemia, a chronic disease with chronic anemia, is caused by mutations in the β-globin gene, leading to reduced levels or complete deficiency of β-globin chain... (Review)
Review
Thalassemia, a chronic disease with chronic anemia, is caused by mutations in the β-globin gene, leading to reduced levels or complete deficiency of β-globin chain synthesis. Patients with β-thalassemia display variable clinical severity which ranges from asymptomatic features to severe transfusion-dependent anemia and complications in multiple organs. They not only are at increased risk of blood-borne infections resulting from multiple transfusions, but they also show enhanced susceptibility to infections as a consequence of coexistent immune deficiency. Enhanced susceptibility to infections in β-thalassemia patients is associated with the interplay of several complex biological processes. β-thalassemia-related abnormalities of the innate immune system include decreased levels of complement, properdin, and lysozyme, reduced absorption and phagocytic ability of polymorphonuclear neutrophils, disturbed chemotaxis, and altered intracellular metabolism processes. According to available literature data, immunological abnormalities observed in patients with thalassemia can be caused by both the disease itself as well as therapies. The most important factors promoting such alterations involve iron overload, phenotypical and functional abnormalities of immune system cells resulting from chronic inflammation oxidative stress, multiple blood transfusion, iron chelation therapy, and splenectomy. Unravelling the mechanisms underlying immune deficiency in β-thalassemia patients may enable the designing of appropriate therapies for this group of patients.
Topics: Adaptive Immunity; Biomarkers; Disease Susceptibility; Genetic Predisposition to Disease; Humans; Immune System; Immunity, Innate; beta-Thalassemia
PubMed: 34575839
DOI: 10.3390/ijms22189677 -
Molecular Medicine (Cambridge, Mass.) Jan 2022Biofilm is a community of bacteria embedded in an extracellular matrix, which can colonize different human cells and tissues and subvert the host immune reactions by... (Review)
Review
BACKGROUND
Biofilm is a community of bacteria embedded in an extracellular matrix, which can colonize different human cells and tissues and subvert the host immune reactions by preventing immune detection and polarizing the immune reactions towards an anti-inflammatory state, promoting the persistence of biofilm-embedded bacteria in the host.
MAIN BODY OF THE MANUSCRIPT
It is now well established that the function of immune cells is ultimately mediated by cellular metabolism. The immune cells are stimulated to regulate their immune functions upon sensing danger signals. Recent studies have determined that immune cells often display distinct metabolic alterations that impair their immune responses when triggered. Such metabolic reprogramming and its physiological implications are well established in cancer situations. In bacterial infections, immuno-metabolic evaluations have primarily focused on macrophages and neutrophils in the planktonic growth mode.
CONCLUSION
Based on differences in inflammatory reactions of macrophages and neutrophils in planktonic- versus biofilm-associated bacterial infections, studies must also consider the metabolic functions of immune cells against biofilm infections. The profound characterization of the metabolic and immune cell reactions could offer exciting novel targets for antibiofilm therapy.
Topics: Animals; Biofilms; Biomarkers; Disease Management; Disease Susceptibility; Energy Metabolism; Host-Pathogen Interactions; Humans; Immune System; Infections; Neoplasms; Organ Specificity
PubMed: 35093033
DOI: 10.1186/s10020-022-00435-2 -
Frontiers in Immunology 2021
Topics: Animals; Disease Susceptibility; Host-Parasite Interactions; Humans; Nerve Tissue; Organ Specificity; Parasites; Tropism
PubMed: 34659274
DOI: 10.3389/fimmu.2021.775666 -
Aging Cell Oct 2023Parkinson's disease (PD) is a neurodegenerative disorder associated with α-synuclein aggregation and dopaminergic neuron loss in the midbrain. There is evidence that...
Parkinson's disease (PD) is a neurodegenerative disorder associated with α-synuclein aggregation and dopaminergic neuron loss in the midbrain. There is evidence that psychological stress promotes PD progression by enhancing glucocorticoids-related oxidative damage, however, the mechanisms involved are unknown. The present study demonstrated that plasma membrane phospholipid peroxides, as determined by phospholipidomics, triggered ferroptosis in dopaminergic neurons, which in turn contributed to stress exacerbated PD-like motor disorder in mice overexpressing mutant human α-synuclein. Using hormonomics, we identified that stress stimulated corticosteroid release and promoted 15-lipoxygenase-1 (ALOX15)-mediated phospholipid peroxidation. ALOX15 was upregulated by α-synuclein overexpression and acted as a fundamental risk factor in the development of chronic stress-induced parkinsonism and neurodegeneration. Further, we demonstrated the mechanism by which corticosteroids activated the PKC pathway and induced phosphatidylethanolamine-binding protein-1 (PEBP1) to form a complex with ALOX15, thereby facilitating ALOX15 to locate on the plasma membrane phospholipids. A natural product isolated from herbs, leonurine, was screened with activities of inhibiting the ALOX15/PEBP1 interaction and thereby attenuating membrane phospholipid peroxidation. Collectively, our findings demonstrate that stress increases the susceptibility of PD by driving membrane lipid peroxidation of dopaminergic neurons and suggest the ALOX15/PEBP1 complex as a potential intervention target.
Topics: Mice; Humans; Animals; Parkinson Disease; alpha-Synuclein; Dopaminergic Neurons; Disease Susceptibility; Stress, Psychological
PubMed: 37622525
DOI: 10.1111/acel.13970 -
Frontiers in Immunology 2021
Topics: Animals; Disease Susceptibility; Host-Pathogen Interactions; Humans; Immunity; Skin Diseases, Infectious; Skin Physiological Phenomena
PubMed: 35095901
DOI: 10.3389/fimmu.2021.810059 -
The American Journal of Psychiatry Jan 2023
Topics: Humans; Psychotic Disorders; Schizophrenia; Disease Susceptibility
PubMed: 36587271
DOI: 10.1176/appi.ajp.20220934 -
European Respiratory Review : An... Dec 2014Past epidemiological observations and recent molecular studies suggest that chronic obstructive pulmonary disease (COPD) and lung cancer are closely related diseases,... (Comparative Study)
Comparative Study Review
Past epidemiological observations and recent molecular studies suggest that chronic obstructive pulmonary disease (COPD) and lung cancer are closely related diseases, resulting from overlapping genetic susceptibility and exposure to aero-pollutants, primarily cigarette smoke. Statistics from the American Lung Association and American Cancer Society reveal that mortality from COPD and lung cancer are lowest in Hispanic subjects and generally highest in African American subjects, with mortality in non-Hispanic white subjects and Asian subjects in between. This observation, described as the “Hispanic paradox”, persists after adjusting for confounding variables, notably smoking exposure and sociodemographic factors. While differences in genetic predisposition might underlie this observation, differences in diet remain a possible explanation. Such a hypothesis is supported by the observation that a diet high in fruit and vegetables has been shown to confer a protective effect on both COPD and lung cancer. In this article, we hypothesise that a diet rich in legumes may explain, in part, the Hispanic paradox, given the traditionally high consumption of legumes (beans and lentils) by Hispanic subjects. Legumes are very high in fibre and have recently been shown to attenuate systemic inflammation significantly, which has previously been linked to susceptibility to COPD and lung cancer in large prospective studies. A similar protective effect could be attributed to the consumption of soy products (from soybeans) in Asian subjects, for whom a lower incidence of COPD and lung cancer has also been reported. This hypothesis requires confirmation in cohort studies and randomised control trials, where the effects of diet on outcomes can be carefully examined in a prospective study design.
Topics: Black or African American; Asian; Diet; Disease Susceptibility; Fabaceae; Genetic Predisposition to Disease; Hispanic or Latino; Humans; Incidence; Inflammation; Lung Neoplasms; Pulmonary Disease, Chronic Obstructive; Risk Factors; White People
PubMed: 25445942
DOI: 10.1183/09059180.00000814 -
Journal of Neuroinflammation Jan 2017Epilepsy is a common and debilitating consequence of traumatic brain injury (TBI). Seizures contribute to progressive neurodegeneration and poor functional and... (Review)
Review
BACKGROUND
Epilepsy is a common and debilitating consequence of traumatic brain injury (TBI). Seizures contribute to progressive neurodegeneration and poor functional and psychosocial outcomes for TBI survivors, and epilepsy after TBI is often resistant to existing anti-epileptic drugs. The development of post-traumatic epilepsy (PTE) occurs in a complex neurobiological environment characterized by ongoing TBI-induced secondary injury processes. Neuroinflammation is an important secondary injury process, though how it contributes to epileptogenesis, and the development of chronic, spontaneous seizure activity, remains poorly understood. A mechanistic understanding of how inflammation contributes to the development of epilepsy (epileptogenesis) after TBI is important to facilitate the identification of novel therapeutic strategies to reduce or prevent seizures. BODY: We reviewed previous clinical and pre-clinical data to evaluate the hypothesis that inflammation contributes to seizures and epilepsy after TBI. Increasing evidence indicates that neuroinflammation is a common consequence of epileptic seizure activity, and also contributes to epileptogenesis as well as seizure initiation (ictogenesis) and perpetuation. Three key signaling factors implicated in both seizure activity and TBI-induced secondary pathogenesis are highlighted in this review: high-mobility group box protein-1 interacting with toll-like receptors, interleukin-1β interacting with its receptors, and transforming growth factor-β signaling from extravascular albumin. Lastly, we consider age-dependent differences in seizure susceptibility and neuroinflammation as mechanisms which may contribute to a heightened vulnerability to epileptogenesis in young brain-injured patients.
CONCLUSION
Several inflammatory mediators exhibit epileptogenic and ictogenic properties, acting on glia and neurons both directly and indirectly influence neuronal excitability. Further research is required to establish causality between inflammatory signaling cascades and the development of epilepsy post-TBI, and to evaluate the therapeutic potential of pharmaceuticals targeting inflammatory pathways to prevent or mitigate the development of PTE.
Topics: Animals; Brain Injuries, Traumatic; Disease Susceptibility; Epilepsy; Humans; Inflammation; Seizures; Signal Transduction
PubMed: 28086980
DOI: 10.1186/s12974-016-0786-1