RESUMO
Diabetes is associated with numerous comorbidities, one of which is increased vulnerability to infections. This review will focus on how diabetes mellitus (DM) affects the immune system and its various components, leading to the impaired proliferation of immune cells and the induction of senescence. We will explore how the pathology of diabetes-induced immune dysfunction may have similarities to the pathways of "inflammaging", a persistent low-grade inflammation common in the elderly. Inflammaging may increase the likelihood of conditions such as rheumatoid arthritis (RA) and periodontitis at a younger age. Diabetes affects bone marrow composition and cellular senescence, and in combination with advanced age also affects lymphopoiesis by increasing myeloid differentiation and reducing lymphoid differentiation. Consequently, this leads to a reduced immune system response in both the innate and adaptive phases, resulting in higher infection rates, reduced vaccine response, and increased immune cells' senescence in diabetics. We will also explore how some diabetes drugs induce immune senescence despite their benefits on glycemic control.
Assuntos
Diabetes Mellitus , Humanos , Diabetes Mellitus/imunologia , Diabetes Mellitus/patologia , Animais , Senescência Celular/imunologia , Inflamação/imunologia , Inflamação/patologia , Sistema Imunitário/imunologiaRESUMO
BACKGROUND: Many studies have identified changes in the brain associated with obsessive-compulsive disorder (OCD), but few have examined the relationship between genetic determinants of OCD and brain variation.AimsWe present the first genome-wide investigation of overlapping genetic risk for OCD and genetic influences on subcortical brain structures. METHOD: Using single nucleotide polymorphism effect concordance analysis, we measured genetic overlap between the first genome-wide association study (GWAS) of OCD (1465 participants with OCD, 5557 controls) and recent GWASs of eight subcortical brain volumes (13 171 participants). RESULTS: We found evidence of significant positive concordance between OCD risk variants and variants associated with greater nucleus accumbens and putamen volumes. When conditioning OCD risk variants on brain volume, variants influencing putamen, amygdala and thalamus volumes were associated with risk for OCD. CONCLUSIONS: These results are consistent with current OCD neurocircuitry models. Further evidence will clarify the relationship between putamen volume and OCD risk, and the roles of the detected variants in this disorder.Declaration of interestThe authors have declared that no competing interests exist.
Assuntos
Variação Genética , Núcleo Accumbens/fisiopatologia , Transtorno Obsessivo-Compulsivo/genética , Putamen/fisiopatologia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Imageamento por Ressonância Magnética , Masculino , Transtorno Obsessivo-Compulsivo/patologia , Tamanho do Órgão , Polimorfismo de Nucleotídeo ÚnicoAssuntos
Fluordesoxiglucose F18 , Neoplasias Renais/diagnóstico por imagem , Linfoma de Células B/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Neoplasias Renais/tratamento farmacológico , Linfoma de Células B/tratamento farmacológico , Insuficiência Renal/diagnóstico por imagem , Insuficiência Renal/etiologiaRESUMO
The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.