Combined Use of Intranasal Methylprednisolone and Allopregnanolone: Revisiting Anti-inflammatory and Remyelinating Treatment in a Murine Model of Multiple Sclerosis.

Background: Multiple sclerosis (MS) is a demyelinating, neuroinflammatory, progressive disease that severely affects human health of young adults. Neuroinflammation (NI) and demyelination, as well as their interactions, are key therapeutic targets to halt or slow disease progression. Potent steroidal anti-inflammatory drugs such as methylprednisolone (MP) and remyelinating neurosteroids such as allopregnanolone (ALLO) could be co-administered intranasally to enhance their efficacy by providing direct access to the central nervous system (CNS).

CuO Nanoparticles as Nanocarriers and Its Antibacterial Efficacy.

In this study, CuO nanoparticles were synthesized using the sol-gel technique and subsequently functionalized with extracts from plants of the Rauvolfioideae subfamily and citrus fruits. Comprehensive characterization techniques, including UV-Vis spectroscopy, FT-IR, XRD, BET, SEM, and TEM, were employed to evaluate the structural and surface properties of the synthesized nanoparticles. The results demonstrated that both functionalized CuO nanoparticles exhibit mesoporous structures, as confirmed by nitrogen adsorption-desorption isotherms and the pore size distribution analysis.

Protective effect of (E)-(2,4-dihydroxy)-α-aminocinnamic acid, a hydroxy cinnamic acid derivative, in an ulcerative colitis model induced by TNBS.

Ulcerative colitis (UC) is a multifactorial disease that causes long-lasting inflammation and ulcers in the digestive tract. UC is the most common form of inflammatory bowel disease (IBD). The current treatment for mild-to-moderate UC involves the use of 5-aminosalicylates (5-ASA), but much of this compound is unabsorbed and metabolized by N-acetylation.

Morin improves learning and memory in healthy adult mice.

Background: Morin is a flavonoid found in many edible fruits. The hippocampus and entorhinal cortex play crucial roles in memory formation and consolidation. This study aimed to characterize the effect of morin on recognition and space memory in healthy C57BL/6 adult mice and explore the underlying molecular mechanism.

Inhaled Litsea glaucescens K. (Lauraceae) leaves' essential oil has anxiolytic and antidepressant-like activity in mice by BDNF pathway activation.

Ethnopharmacological Relevance: Litsea glaucescens K. (Lauraceae) is a small tree from the Mexican and Central American temperate forests, named as "Laurel". Its aromatic leaves are ordinarily consumed as condiments, but also are important in Mexican Traditional Medicine, and among the most important non wood forest products in this area.

Molecular dynamics simulations depict structural motions of the whole human aryl hydrocarbon receptor influencing its binding of ligands and HSP90.

The aryl hydrocarbon receptor (AhR) has broad biological functions when its ligands activate it; the non-binding interactions with AhR have not been fully elucidated due to the absence of a complete tridimensional (3D) structure. Therefore, utilization of the whole 3D structure from Homo sapiens AhR by in silico studies will allow us to better study and analyze the binding mode of its full and partial agonists, and antagonists, as well as its interaction with the HSP90 chaperone. The 3D AhR structure was obtained from I-TASSER and subjected to molecular dynamics (MD) simulations to obtain different structural conformations and determine the most populated AhR conformer by clustering analyses.

PLGA-TiO as a Carrier System for Drug Release.

This paper reports the results of the PLGA-TiO nanocomposite regarding the green synthesis of titanium dioxide nanoparticles using a natural extract, its characterization, and encapsulation with poly(lactic-co-glycolic acid) (PLGA). UV-visible spectrometry was used for the identification of terpenes present in the extracts. The morphology of the nanoparticles was determined by scanning electron microscopy.

Dietary Fiber Modulates the Release of Gut Bacterial Products Preventing Cognitive Decline in an Alzheimer's Mouse Model.

Fiber intake is associated with a lower risk for Alzheimer´s disease (AD) in older adults. Intake of plant-based diets rich in soluble fiber promotes the production of short-chain fatty acids (SCFAs: butyrate, acetate, propionate) by gut bacteria. Butyrate administration has antiinflammatory actions, but propionate promotes neuroinflammation.

A Study of Zn-Ca Nanocomposites and Their Antibacterial Properties.

This study aimed to develop Ca doped ZnO nanoparticles (NPs) and investigate their antibacterial properties against microorganisms of dental interest. Zn-Ca NPs were synthesized by the sol-gel method with different concentrations of Ca (1, 3, and 5 wt. %) and subsequently characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), UV-vis spectroscopy and Fourier transform infrared spectroscopy (FT-IR).

Intranasal Methylprednisolone Ameliorates Neuroinflammation Induced by Chronic Toluene Exposure.

Inhalants are chemical substances that induce intoxication, and toluene is the main component of them. Increasing evidence indicates that a dependence on inhalants involves a state of chronic stress associated to the activation of immune cells in the central nervous system and release of proinflammatory mediators, especially in some brain areas such as the nucleus accumbens and frontal cortex, where the circuits of pleasure and reward are. In this study, anti-neuroinflammatory treatment based on a single dose of intranasal methylprednisolone was assessed in a murine model of chronic toluene exposure.

Tert-butyl-(4-hydroxy-3-((3-(2-methylpiperidin-yl)propyl)carbamoyl)phenyl)carbamate Has Moderated Protective Activity in Astrocytes Stimulated with Amyloid Beta 1-42 and in a Scopolamine Model.

Alzheimer's disease (AD) is a neurodegenerative disease with no cure nowadays; there is no treatment either to prevent or to stop its progression. In vitro studies suggested that tert-butyl-(4-hydroxy-3-((3-(2-methylpiperidin-yl)propyl)carbamoyl)phenyl) carbamate named the compound can act as both β-secretase and an acetylcholinesterase inhibitor, preventing the amyloid beta peptide (Aβ) aggregation and the formation of fibrils (fAβ) from Aβ. This work first aimed to assess in in vitro studies to see whether the death of astrocyte cells promoted by Aβ could be prevented.

Serum Repressor Element-1 Silencing Transcription Factor Levels in Alzheimer's Patients from a National Institute of Health in Mexico City, Elderly and Young Controls.

Background: Decreased levels of repressor element-1 silencing transcription (REST) factor in the brain, plasma, and neuronderived exosomes are associated with Alzheimer's disease (AD).

Objective: The objective of the study was to test the viability of serum REST as a possible blood-based biomarker for AD, comparing serum REST levels in AD patients from a National Institute of Health in Mexico City (with different levels of severity and comorbidities), with elderly controls (EC) and young controls (YC).

Methods: We used an enzyme-linked immunosorbent assay to determine serum REST levels in AD patients (n = 28), EC (n = 19), and YC (n = 24); the AD patients were classified by dementia severity and comorbidities (depression and microangiopathy) using clinimetric tests and magnetic resonance imaging.

Aryl Hydrocarbon Receptor in Post-Mortem Hippocampus and in Serum from Young, Elder, and Alzheimer's Patients.

One of the characteristics of the cerebral aging process is the presence of chronic inflammation through glial cells, which is particularly significant in neurodegeneration. On the other hand, it has been demonstrated that the aryl hydrocarbon receptor (AHR) participates in the inflammatory response. Currently, evidence in animal models shows that the hallmarks of aging are associated with changes in the AHR levels.

Neuroprotective Effects of Apocynin and Galantamine During the Chronic Administration of Scopolamine in an Alzheimer's Disease Model.

Alzheimer's disease (AD) is one of the most complicated neurodegenerative diseases, and several hypotheses have been associated with its development and progression, such as those involving glucose hypometabolism, the cholinergic system, calcium imbalance, inflammation, oxidative imbalance, microtubule instability, and the amyloid cascade, several of which are related to oxidative stress (free radical generation), which contributes to neuronal death. Therefore, several efforts have been made to establish a sporadic AD model that takes into account these hypotheses. One model that replicates the increase in amyloid beta (Aβ) and oxidative stress in vivo is the scopolamine model.

Injectable and Gellable Chitosan Formulations Filled with Cellulose Nanofibers for Intervertebral Disc Tissue Engineering.

The development of non-cellularized injectable suspensions of viscous chitosan (CHI) solutions (1.7⁻3.3% (/)), filled with cellulose nanofibers (CNF) (0.

Cortical Astrocytes Acutely Exposed to the Monomethylarsonous Acid (MMA) Show Increased Pro-inflammatory Cytokines Gene Expression that is Consistent with APP and BACE-1: Over-expression.

Long-term exposure to inorganic arsenic (iAs) through drinking water has been associated with cognitive impairment in children and adults; however, the related pathogenic mechanisms have not been completely described. Increased or chronic inflammation in the brain is linked to impaired cognition and neurodegeneration; iAs induces strong inflammatory responses in several cells, but this effect has been poorly evaluated in central nervous system (CNS) cells. Because astrocytes are the most abundant cells in the CNS and play a critical role in brain homeostasis, including regulation of the inflammatory response, any functional impairment in them can be deleterious for the brain.

Activation of AHR mediates the ubiquitination and proteasome degradation of c-Fos through the induction of Ubcm4 gene expression.

The ubiquitin-proteasome system (UPS) is a specific, non-lysosomal pathway responsible for the controlled degradation of abnormal and short-half-life proteins. Despite its relevance in cell homeostasis, information regarding control of the UPS component gene expression is lacking. Data from a recent study suggest that the aryl hydrocarbon receptor (AHR), a ligand-dependent transcription factor, might control the expression of several genes encoding for UPS proteins.

Receptor for AGEs (RAGE) as mediator of NF-kB pathway activation in neuroinflammation and oxidative stress.

Recently, it has been proposed that the receptor for advanced glycation end-products (RAGE) plays a crucial role in damaging cellular processes, such as neuroinflammation, neurodegeneration, excitotoxicity and oxidative stress. RAGE is a multiligand receptor belonging to the immunoglobulin superfamily of cell surface molecules acting as a counter-receptor for diverse molecules. Engagement of RAGE converts a brief pulse of cellular activation into sustained cellular dysfunction and tissue damage.

Tetramerization-defects of p53 result in aberrant ubiquitylation and transcriptional activity.

The tumor suppressor p53 regulates the expression of genes involved in cell cycle progression, senescence and apoptosis. Here, we investigated the effect of single point mutations in the oligomerization domain (OD) on tetramerization, transcription, ubiquitylation and stability of p53. As predicted by docking and molecular dynamics simulations, p53 OD mutants show functional defects on transcription, Mdm2-dependent ubiquitylation and 26S proteasome-mediated degradation.

Antioxidant properties of xanthones from Calophyllum brasiliense: prevention of oxidative damage induced by FeSO₄.

Background: Reactive oxygen species (ROS) are important mediators in a number of degenerative diseases. Oxidative stress refers to the imbalance between the production of ROS and the ability to scavenge these species through endogenous antioxidant systems. Since antioxidants can inhibit oxidative processes, it becomes relevant to describe natural compounds with antioxidant properties which may be designed as therapies to decrease oxidative damage and stimulate endogenous cytoprotective systems.

Multiple molecular and cellular mechanisms of action of lycopene in cancer inhibition.

Epidemiological studies suggest that including fruits, vegetables, and whole grains in regular dietary intake might prevent and reverse cellular carcinogenesis, reducing the incidence of primary tumours. Bioactive components present in food can simultaneously modulate more than one carcinogenic process, including cancer metabolism, hormonal balance, transcriptional activity, cell-cycle control, apoptosis, inflammation, angiogenesis and metastasis. Some studies have shown an inverse correlation between a diet rich in fruits, vegetables, and carotenoids and a low incidence of different types of cancer.

Selenium-induced antioxidant protection recruits modulation of thioredoxin reductase during excitotoxic/pro-oxidant events in the rat striatum.

Selenium (Se) is a crucial element exerting antioxidant and neuroprotective effects in different toxic models. It has been suggested that Se acts through selenoproteins, of which thioredoxin reductase (TrxR) is relevant for reduction of harmful hydroperoxides and maintenance of thioredoxin (Trx) redox activity. Of note, the Trx/TrxR system remains poorly studied in toxic models of degenerative disorders.

Isolation of ubiquitylated proteins using tandem ubiquitin-binding entities.

Studying postubiquitylation events has always been a difficult task due to the labile nature of these posttranslational modifications. When utilized in tandem, ubiquitin-binding entities (TUBEs) not only increase up to thousand times the affinity for poly-ubiquitin chains but also protect ubiquitylated proteins from the action of the proteasome and de-ubiquitylating enzymes.

Role of monoubiquitylation on the control of IκBα degradation and NF-κB activity.

The NF-κB pathway is regulated by multiple post-translational modifications including phosphorylation, ubiquitylation and SUMOylation. Many of these modifications act on the natural inhibitor IκBα modulating its capacity to control signal-mediated NF-κB activity. While the canonical pathway involving the phosphorylation and polyubiquitylation of IκBα has been well characterized, the role of these post-translational modifications in the control of basal NF-κB activity has not been deeply explored.