Single-nucleotide polymorphism analysis accurately predicts multiple impairments in hippocampal activity and memory performance in a murine model of idiopathic autism.

Autism spectrum disorder (ASD) comprises alterations in brain anatomy and physiology that ultimately affect information processing and behavior. In most cases, autism is considered idiopathic, involving alterations in numerous genes whose functions are not extensively documented. We evaluated the C58/J mouse strain as an idiopathic model of ASD, emphasizing synaptic transmission as the basis of information processing.

Environmental Enrichment Prevents Gut Dysbiosis Progression and Enhances Glucose Metabolism in High-Fat Diet-Induced Obese Mice.

Obesity is a global health concern implicated in numerous chronic degenerative diseases, including type 2 diabetes, dyslipidemia, and neurodegenerative disorders. It is characterized by chronic low-grade inflammation, gut microbiota dysbiosis, insulin resistance, glucose intolerance, and lipid metabolism disturbances. Here, we investigated the therapeutic potential of environmental enrichment (EE) to prevent the progression of gut dysbiosis in mice with high-fat diet (HFD)-induced metabolic syndrome.

Exploring the Significance of Microglial Phenotypes and Morphological Diversity in Neuroinflammation and Neurodegenerative Diseases: From Mechanisms to Potential Therapeutic Targets.

Studying various microglial phenotypes and their functions in neurodegenerative diseases is crucial due to the intricate nature of their phenomics and their vital immunological role. Microglia undergo substantial phenomic changes, encompassing morphological, transcriptional, and functional aspects, resulting in distinct cell types with diverse structures, functions, properties, and implications. The traditional classification of microglia as ramified, M1 (proinflammatory), or M2 (anti-inflammatory) phenotypes is overly simplistic, failing to capture the wide range of recently identified microglial phenotypes in various brain regions affected by neurodegenerative diseases.

Negative Regulation of Autophagy during Macrophage Infection by BCG via Protein Kinase C Activation.

() employs various strategies to manipulate the host's cellular machinery, overriding critical molecular mechanisms such as phagosome-lysosome fusion, which are crucial for its destruction. The Protein Kinase C (PKC) signaling pathways play a key role in regulating phagocytosis. Recent research in Interferon-activated macrophages has unveiled that PKC phosphorylates Coronin-1, leading to a shift from phagocytosis to micropinocytosis, ultimately resulting in destruction.

Insights into Zika Virus Pathogenesis and Potential Therapeutic Strategies.

Zika virus (ZIKV) has emerged as a significant public health threat, reaching pandemic levels in 2016. Human infection with ZIKV can manifest as either asymptomatic or as an acute illness characterized by symptoms such as fever and headache. Moreover, it has been associated with severe neurological complications in adults, including Guillain-Barre syndrome, and devastating fetal abnormalities, like microcephaly.

Klf10 favors Mycobacterium tuberculosis survival by impairing IFN-γ production and preventing macrophages reprograming to macropinocytosis.

Mycobacterium tuberculosis has developed diverse mechanisms to survive inside phagocytic cells, such as macrophages. Phagocytosis is a key process in eliminating invading pathogens; thus, M. tuberculosis efficiently disrupts phagosome maturation to ensure infection.

Microglial activation in Alzheimer's disease: The role of flavonoids and microRNAs.

Alzheimer's disease (AD) is the most common form of senile dementia and is characterized by progressive cognitive impairment and neuronal degeneration. Microglial activation is an important pathologic hallmark of AD. During disease progression, microglial cells switch from an alternative or anti-inflammatory and neuroprotective profile (M2) to a classic or proinflammatory and neurotoxic profile (M1).

Protein lysine acetylation and its role in different human pathologies: a proteomic approach.

Introduction: Lysine acetylation is a reversible post-translational modification (PTM) regulated through the action of specific types of enzymes: lysine acetyltransferases (KATs) and lysine deacetylases (HDACs), in addition to bromodomains, which are a group of conserved domains which identify acetylated lysine residues, several of the players in the process of protein acetylation, including enzymes and bromodomain-containing proteins, have been related to the progression of several diseases. The combination of high-resolution mass spectrometry-based proteomics, and immunoprecipitation to enrich acetylated peptides has contributed in recent years to expand the knowledge about this PTM described initially in histones and nuclear proteins, and is currently reported in more than 5000 human proteins, that are regulated by this PTM.

Areas Covered: This review presents an overview of the main participant elements, the scenario in the development of protein lysine acetylation, and its role in different human pathologies.

Synergism and Subadditivity of Verbascoside-Lignans and -Iridoids Binary Mixtures Isolated from Benth. on NF-κB/AP-1 Inhibition Activity.

Pharmacodynamic interactions between plant isolated compounds are important to understand the mode of action of an herbal extract to formulate or create better standardized extracts, phytomedicines, or phytopharmaceuticals. In this work, we propose binary mixtures using a leader compound to found pharmacodynamic interactions in inhibition of the NF-κB/AP-1 pathway using RAW-Blue™ cells. Eight compounds were isolated from , four were new furofuran-type lignans for the species magnolin, eudesmin, sesamin, and kobusin.

A dysfunctional family environment and a high body fat percentage negatively affect telomere length in Mexican boys aged 8-10 years.

Aim: The aim of this study was to determine whether a direct relationship existed between absolute telomere length (aTL), obesity and familial functionality in a group of Mexican children.

Methods: We recruited 134 children (52% boys) aged 8-10 years during regular primary care check-ups in 2016 and evaluated physical activity (PA), feeding practices, anthropometrics, body fat percentage (BF%) and family dysfunction. Optimised quantitative PCR determined aTL from genomic deoxyribonucleic acid isolated from saliva samples.

Tumor Necrosis Factor-Induced miR-146a Upregulation Promotes Human Lung Adenocarcinoma Metastasis by Targeting Merlin.

Inflammation plays a key role in carcinogenesis and metastasis. This process involves the inactivation of tumor suppressor molecules, yet the molecular mechanisms by which inflammation impairs tumor suppressors are not completely understood. In this study, we show that proinflammatory signals such as tumor necrosis factor (TNF) support lung cancer metastasis by reducing the levels of the tumor suppressor Merlin through regulation of miR-146a.

Nlrp1b1 negatively modulates obesity-induced inflammation by promoting IL-18 production.

Obesity-induced inflammation, triggered by lipid-mediated activation of the Nlrp3 inflammasome, results in glucose metabolism alterations and type 2 diabetes. This knowledge has been generated using animals deficient for any of the different components of this inflammasome (Caspase-1, Asc or Nlrp3) in the C57BL/6 background. Unlike C57BL/6 mice, which carry allele 2 of the Nlrp1b gene (Nlrp1b2), Balb/c mice that carry allele 1 (Nlrp1b1) are less prone to develop alterations in the glucose metabolism when fed with a high fat diet.

A Malva parviflora´s fraction prevents the deleterious effects resulting from neuroinflammation.

Neuroinflammation, a centralized immune response, is a physiological process by which the organism attempts to remove an injurious stimulus in the central nervous system. Nonetheless, it is known that chronic inflammatory processes play an important role in the onset and progression of neurodegenerative disorders, such as Alzheimer´s disease (AD). Based on this, new strategies to treat AD have been proposed.

Malva parviflora extract ameliorates the deleterious effects of a high fat diet on the cognitive deficit in a mouse model of Alzheimer's disease by restoring microglial function via a PPAR-γ-dependent mechanism.

Background: Alzheimer's disease (AD) is a neuropathology strongly associated with the activation of inflammatory pathways. Accordingly, inflammation resulting from obesity exacerbates learning and memory deficits in humans and in animal models of AD. Consequently, the long-term use of non-steroidal anti-inflammatory agents diminishes the risk for developing AD, but the side effects produced by these drugs limit their prophylactic use.

Mycobacterium bovis BCG promotes IL-10 expression by establishing a SYK/PKCα/β positive autoregulatory loop that sustains STAT3 activation.

Mycobacterium ensures its survival inside macrophages and long-term infection by subverting the innate and adaptive immune response through the modulation of cytokine gene expression profiles. Different Mycobacterium species promote the expression of TGFβ and IL-10, which, at the early stages of infection, block the formation of the phagolysosome, thereby securing mycobacterial survival upon phagocytosis, and at later stages, antagonize IFNγ production and functions. Despite the key role of IL-10 in mycobacterium infection, the signal transduction pathways leading to IL-10 expression in infected macrophages are poorly understood.

Autophagy impairment by caspase-1-dependent inflammation mediates memory loss in response to β-Amyloid peptide accumulation.

β-Amyloid peptide accumulation in the cortex and in the hippocampus results in neurodegeneration and memory loss. Recently, it became evident that the inflammatory response triggered by β-Amyloid peptides promotes neuronal cell death and degeneration. In addition to inflammation, β-Amyloid peptides also induce alterations in neuronal autophagy, eventually leading to neuronal cell death.

Activation of the Wnt Pathway by : A Wnt-Wnt Situation.

(), an intracellular pathogenic Gram-positive bacterium, is the cause of tuberculosis (TB), a major worldwide human infectious disease. The innate immune system is the first host defense against . The recognition of this pathogen is mediated by several classes of pattern recognition receptors expressed on the host innate immune cells, including Toll-like receptors, Nod-like receptors, and C-type lectin receptors like Dectin-1, the Mannose receptor, and DC-SIGN.

LIM homeobox protein 5 (Lhx5) is essential for mamillary body development.

The mamillary body (MM) is a group of hypothalamic nuclei related to memory and spatial navigation that interconnects hippocampal, thalamic, and tegmental regions. Here we demonstrate that Lhx5, a LIM-HD domain transcription factor expressed early in the developing posterior hypothalamus, is required for the generation of the MM and its derived tracts. The MM markers Foxb1, Sim2, and Lhx1 are absent in Lhx5 knock-out mice from early embryonic stages, suggesting abnormal specification of this region.

Merlin negative regulation by miR-146a promotes cell transformation.

Inactivation of the tumor suppressor Merlin, by deleterious mutations or by protein degradation via sustained growth factor receptor signaling-mediated mechanisms, results in cell transformation and tumor development. In addition to these mechanisms, here we show that, miRNA-dependent negative regulation of Merlin protein levels also promotes cell transformation. We provide experimental evidences showing that miR-146a negatively regulates Merlin protein levels through its interaction with an evolutionary conserved sequence in the 3´ untranslated region of the NF2 mRNA.

Negative regulation of the inflammasome: keeping inflammation under control.

In addition to its roles in controlling infection and tissue repair, inflammation plays a critical role in diverse and distinct chronic diseases, such as cancer, metabolic syndrome, and neurodegenerative disorders, underscoring the harmful effect of an uncontrolled inflammatory response. Regardless of the nature of the stimulus, initiation of the inflammatory response is mediated by assembly of a multimolecular protein complex called the inflammasome, which is responsible for the production of inflammatory cytokines, such as interleukin-1β (IL-1β) and IL-18. The different stimuli and mechanisms that control inflammasome activation are fairly well understood, but the mechanisms underlying the control of undesired inflammasome activation and its inactivation remain largely unknown.