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Trends in Molecular Medicine Nov 2020The accumulation of cellular and environmental microparticles has been linked to many diseases associated with tissue inflammation. These particulate-driven diseases... (Review)
Review
The accumulation of cellular and environmental microparticles has been linked to many diseases associated with tissue inflammation. These particulate-driven diseases include joint, lung, kidney, cardiovascular, and neurodegenerative disorders. Recently a conserved proinflammatory inflammasome signaling pathway elicited by such microparticles has become apparent. Here, we review disease-promoting microparticles and the mechanisms by which they trigger activation of the inflammasome complexes responsible for generating bioactive interleukin-1β (IL-1β) and inducing cell death. We highlight how microparticle-induced inflammasome and cell death responses diverge from canonical inflammasome activators, and discuss the preclinical and clinical targeting of inflammasomes to treat microparticle-driven diseases.
Topics: Animals; Cell Communication; Cell Death; Cell-Derived Microparticles; Cellular Microenvironment; Disease Susceptibility; Humans; Inflammasomes; Interleukin-1beta; NLR Family, Pyrin Domain-Containing 3 Protein; Pyroptosis; Signal Transduction
PubMed: 32646646
DOI: 10.1016/j.molmed.2020.06.005 -
Differentiation; Research in Biological... 2016This review presents published and novel results that define the programming window for diethylstilbestrol (DES)-induced abnormal development of the mouse penis. These... (Review)
Review
This review presents published and novel results that define the programming window for diethylstilbestrol (DES)-induced abnormal development of the mouse penis. These data indicate that DES has its greatest effect during the period of most intense penile morphogenesis, namely postnatal days 0-15 (P0-P15). Pregnant mice and their neonatal pups were injected subcutaneously with 200 ng/gbw DES every other day from embryonic day 12-18 (DES E12-E18), postnatal day 0-10 (DES P0-P10), embryonic day 12 to postnatal day 10 (DES E12-P10), postnatal day 5-15 (DES P5-P15), and postnatal day 10-20 (DES P10-P20). Aged-matched controls received sesame oil vehicle. After euthanasia at 10, 15, 20 and 60 days, penises were analyzed by gross morphology, histology and morphometry. Penises of all 5 groups of DES-treated mice were reduced in size, which was confirmed by morphometric analysis of internal penile structures. The most profound effects were seen in the DES E12-P10, DES P0-P10, and DES P5-P15 groups, thus defining a DES "programming window". For all parameters, DES treatment from P10 to P20 showed the most mild of effects. Adverse effects of DES on the MUMP cartilage and erectile bodies observed shortly after the last DES injection reverted to normality in the DES P5-P15, but not in the E12-P10 and P0-P10 groups, in which MUMP cartilage and erectile body malformations persisted into adulthood, again emphasizing a "window of susceptibility" in the early neonatal period.
Topics: Animals; Animals, Newborn; Diethylstilbestrol; Disease Susceptibility; Estrogens, Non-Steroidal; Female; Humans; Hypospadias; Male; Mice; Morphogenesis; Penis; Pregnancy
PubMed: 26810244
DOI: 10.1016/j.diff.2016.01.004 -
Poultry Science Apr 2019Coccidiosis and necrotic enteritis (NE) are among the most significant diseases affecting the poultry industry. These diseases have become more prominent in the wake of... (Review)
Review
Coccidiosis and necrotic enteritis (NE) are among the most significant diseases affecting the poultry industry. These diseases have become more prominent in the wake of policies to reduce the use of antibiotics in animal production. This has led to more research focused on better understanding the immune system and its responses to pathogen challenge, and thus developing informed strategies to exploit immune responses that can support enhanced disease resistance and growth performance. Some chicken breeds and lines show greater resistance or susceptibility to various diseases, and thus these birds maybe able to shed light on immune processes or pathways that contribute to the more resistant/susceptible state. This review attempts to identify potentially important genes that show some consistency in (relative) up or downregulation in key tissues between the resistant and susceptible chickens. For coccidiosis and NE, relative downregulation of IL-10 and (slightly less consistently) upregulation of IFN-γ appear to be features of more resistant birds. Data for IFN-α, IL-12, and IL-17D are currently less consistent. Gene expression data from NE studies have identified some potentially interesting, perhaps less well understood, immune-related genes (e.g., TCF12, BCL2, IRF2, TRAF3, TAB3, etc.,) that maybe associated with the resistant and/or susceptible phenotype. Salmonella and Campylobacter are important foodborne pathogens harbored by the chicken intestinal tract, while infectious bursal disease and infectious bronchitis are also important viral diseases of poultry. We, therefore, consider whether there are consistent features from resistant/susceptible disease models with these pathogens that relate to findings from the coccidiosis and NE studies. It is not anticipated that ideal immune responses to these pathogens will be identical but rather that consistent elements maybe identified that could help inform breeding or alternative strategies to support general disease resistance and enhanced (and efficient) flock productivity.
Topics: Adaptive Immunity; Animals; Avian Proteins; Chickens; Disease Models, Animal; Disease Resistance; Disease Susceptibility; Gene Expression Regulation; Immunity, Innate; Poultry Diseases
PubMed: 30534980
DOI: 10.3382/ps/pey535 -
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 -
Tierarztliche Praxis. Ausgabe G,... Aug 2020
Topics: Animals; Animals, Newborn; Animals, Suckling; Cattle; Cattle Diseases; Colostrum; Cryptosporidiosis; Disease Susceptibility; Female; Immunity, Maternally-Acquired; Immunoglobulin G
PubMed: 32823335
DOI: 10.1055/a-1166-9049 -
Gene Jul 2023Meningitis is inflammation of the membranes enclosing the brain and spinal cord. It is a fatal disease with severe morbidity and mortality. Mannose binding lectin (MBL)...
BACKGROUND
Meningitis is inflammation of the membranes enclosing the brain and spinal cord. It is a fatal disease with severe morbidity and mortality. Mannose binding lectin (MBL) encoded by MBL2 gene activates complement system through lectin pathway in innate immunity to defense against the infections.
OBJECTIVE
The current study aimed to investigate the promoter and exon 1 variants of MBL2 gene among Egyptian patients having meningitis to explore their role in disease susceptibility.
PATIENTS AND METHODS
This case-control study, included 53 patients and 50 sex and age matched controls. MBL2 genotyping was done using Sanger sequencing.
RESULTS
The frequency of one promoter (c.-290C > G) and four in exon 1 (c.161G > A, c.170G > A, c.154C > T and c.132C > T) as well as another one located in its 5'utranslated part (c.-66C > T) variants were estimated. The incidence of the four individual exonic variants was not significantly different between cases and healthy individuals (all P > 0.05). The promoter variant, c.-290C > G was found in all examined patients (84.9% of the patients in homozygote state and 15.1% of patients in heterozygous state) with a highly significant variance in the prevalence of this variant between cases and control group (p = 0.0001). Additionally, UTR variant (c.-66C > T) was also significantly higher in patients than controls (P = 0.033).In comparison with clinical outcome, it was found that c.170G > A variant named C allele was associated with favorable outcome in the studied patients (P = 0.025).
CONCLUSION
The results obtained showed that the Promoter (c.-290C > G) and UTR (c.-66C > T) variants of MBL2 gene may be potential risk factors for disease susceptibility in Egyptian cases with meningitis. Our results also proposed that c.170G > A (C allele and CC genotype) could affect the severity and play a protective role in these patients. The other genetic variants of MBL2 gene, including c.132C > T, c.161G > A (A > B), and c.154C > T (A > D) that were investigated, did not show any association with susceptibility or severity of meningitis.
Topics: Humans; Case-Control Studies; Disease Susceptibility; Egypt; Mannose-Binding Lectin; Genotype; Meningitis; Genetic Predisposition to Disease
PubMed: 37121343
DOI: 10.1016/j.gene.2023.147442 -
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 -
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 -
Advances in Experimental Medicine and... 2018The predisposing factors to lifestyle-associated diseases are established in the early period of life with underlying gene-environment interaction. Epigenetics is a... (Review)
Review
The predisposing factors to lifestyle-associated diseases are established in the early period of life with underlying gene-environment interaction. Epigenetics is a chemical modification-based genetic mechanism that is affected by various nutritional factors. One-carbon metabolism is a metabolic system associated with methyl residue that is supplied from folic acid. Therefore, from the epigenetic point of view, proper intake of folic acid is important for pregnant women not only to prevent congenital abnormalities such as neural tube defect but also to prevent various adult disorders of the offspring. Dyslipidemia is an important risk factor of coronary heart disease, and epidemiological studies on Dutch winter famine, Jewish holocaust survivors, and Chinese famine suggested that prenatal malnutrition was associated with the dyslipidemia. Recent animal studies revealed that malnutrition in utero causes an epigenetic change in the Pparα gene, which accelerates the activity of delta-6 desaturase and delta-5 desaturase, that potentially induces dyslipidemia in adulthood. It has been known that overnutrition also increased the risk of cardiovascular diseases. Recent animal studies revealed that high-fat diet increased DNA methylation in the promoter region of delta-6 desaturase gene (Fads 2) that downregulates the gene expression in the arterial smooth muscle, which potentially contributes to cardiovascular diseases. Taken together, either insufficient or excessive nutrition alters epigenetic modification of genes that encodes enzymes associated with lipid metabolism. This altered epigenetic state persists during one's lifetime, which is potentially involved in noncommunicable diseases in adulthood.
Topics: Animals; Carbon; DNA Methylation; Disease Susceptibility; Epigenesis, Genetic; Female; Humans; Lipid Metabolism; Metabolic Networks and Pathways; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors
PubMed: 29956189
DOI: 10.1007/978-981-10-5526-3_1