Impact of Glucocorticoid-Associated Stress-Like Conditions on Aquaporin-4 in Cultured Astrocytes and Its Modulation by Adenosine A Receptors.

Astrocytes participate in brain clearance of extracellular proteins and metabolites, through the activity of the water channel aquaporin-4 (AQP4), which can be deregulated in stress-related disorders, impairing brain waste clearance. The present study investigates the impact of dexamethasone (Dexa), a synthetic glucocorticoid used as a simplified in vitro stress model, on astrocytic AQP4 and its modulation by adenosine A receptors (AR), which blockade reverses conditions related with maladaptive stress, such as anxiety and depression. The clearance of proteins in primary astrocytic cultures, assessed using 5 kDa FITC-dextran and 45 kDa TRITC-dextran uptake, was decreased by a 24 h exposure to 100 nM Dexa.

An atomic look at the interface of GHSR and its partners.

G protein-coupled receptors (GPCRs) regulate cellular activity by transducing external signals and selectively coupling them to intracellular partners. Ghrelin receptor (GHSR) has garnered significant interest over the past decade owing to its diverse functional roles. In this study, we simulated five distinct GHSR-partner complexes, including G, G, and arrestin in two conformational states, to investigate the structural determinants of partner coupling.

Effect of hypoxia and KCl depolarization in autofluorescence and ROS changes at the hippocampal CA3 area.

The increasing incidence of neurodegenerative and other diseases is considered to involve an excessive production of reactive oxygen species (ROS). Water supplies are often characterized by excessive organic waste that is decomposed by bacteria, using dissolved oxygen, leading to oxygen depletion. The potassium content of these waters may also affect negatively the mitochondrial metabolism and cellular ROS formation.

Fourier Transform Infrared (FTIR) Spectroscopy as a Tool to Characterize Exercise and Physical Activity: A Systematic Review.

Background: Over the past few decades, the scientific community has recognized the impact of physical activity on health and performance. In parallel, researchers have been actively exploring novel methodologies to analyze the physiological and metabolic responses to exercise. Fourier transform infrared spectroscopy has emerged as a powerful tool in this effort, offering the potential to provide unique insights into exercise-related changes at the molecular level.

Mitochondrial Membrane Potential (ΔΨ) Fluctuations Associated with the Metabolic States of Mitochondria.

The proton electrochemical gradient generated by the respiratory chain activity accounts for over 90% of the available respiratory energy and, as such, its evaluation and accurate measurement regarding total values and fluctuations are an invaluable component of the understanding of mitochondrial function. Consequently, alterations in electric potential across the inner mitochondrial membrane generated by differential protonic accumulation and transport are known as the mitochondrial membrane potential, or Δψ, and are reflective of the functional metabolic status of mitochondria. There are several experimental approaches to measure Δψ, ranging from fluorometric evaluations to electrochemical probes.

Characterization of the Mitochondria Function and Metabolism in Skin Fibroblasts Using the Biolog MitoPlate S-1.

S-1 MitoPlates™ from Biolog enable the characterization of mitochondria's function in live cells by measuring the rates of electron flow into and through the electron transport chain from different NADH or FADH producing metabolic substrates. This technology uses 96-well microplates pre-coated with triplicate repeats of a set of 31 substrates. Those 31 metabolic substrates have different routes of entry into the mitochondria, use different transporters, and are also oxidated by different dehydrogenases, producing reducing equivalents in the form of NADH or FADH.

Unveiling the potential of intranasal delivery of renin-angiotensin system drugs: Insights on the pharmacokinetics of irbesartan.

The therapeutic interest of renin-angiotensin system (RAS) drugs for the treatment of neuroinflammation has been recently acknowledged. Nevertheless, most of them display limited passage across the blood-brain barrier (BBB). Therefore, this study investigated the potential of intranasal (IN) delivery of six RAS drugs to circumvent the BBB and attain the brain, envisioning its future use in central nervous system (CNS) neuroinflammatory diseases, such as Alzheimer's disease (AD).

Effect of bioactive extracts from Eucalyptus globulus leaves in experimental models of Alzheimer's disease.

Current therapies for Alzheimer's disease (AD) do not delay its progression, therefore, novel disease-modifying strategies are urgently needed. Recently, an increasing number of compounds from natural origin with protective properties against AD have been identified. Mixtures or extracts obtained from natural products containing several bioactive compounds have multifunctional properties and have drawn the attention because multiple AD pathways can be simultaneously modulated.

p66Shc Protein-Oxidative Stress Sensor or Redox Enzyme: Its Potential Role in Mitochondrial Metabolism of Human Breast Cancer.

This work presents a comprehensive evaluation of the role of p66Shc protein in mitochondrial physiology in MDA-MB-231 breast cancer cells. The use of human breast cancer cell line MDA-MB-231 and its genetically modified clones (obtained with the use of the CRISPR-Cas9 technique), expressing different levels of p66Shc protein, allowed us to demonstrate how the p66Shc protein affects mitochondrial metabolism of human breast cancer cells. Changes in the level of p66Shc (its overexpression, and overexpressing of its Serine 36-mutated version, as well as the knockout of p66Shc) exert different effects in breast cancer cells.

Exploiting the potential of rivastigmine-melatonin derivatives as multitarget metal-modulating drugs for neurodegenerative diseases.

The multifaceted nature of the neurodegenerative diseases, as Alzheimer's disease (AD) and Parkinson's disease (PD) with several interconnected etiologies, and the absence of effective drugs, led herein to the development and study of a series of multi-target directed ligands (MTDLs). The developed RIV-IND hybrids, derived from the conjugation of an approved anti-AD drug, rivastigmine (RIV), with melatonin analogues, namely indole (IND) derivatives, revealed multifunctional properties, by associating the cholinesterase inhibition of the RIV drug with antioxidant activity, biometal (Cu(II), Zn(II), Fe(III)) chelation properties, inhibition of amyloid-β (Aβ) aggregation (self- and Cu-induced) and of monoamine oxidases (MAOs), as well as neuroprotection capacity in cell models of AD and PD. In particular, two hybrids with hydroxyl-substituted indoles (5a2 and 5a3) could be promising multifunctional compounds that inspire further development of novel anti-neurodegenerative drugs.

Mitochondrial Dynamics and mRNA Translation: A Local Synaptic Tale.

Mitochondria are dynamic organelles that can adjust and respond to different stimuli within a cell. This plastic ability allows them to effectively coordinate several cellular functions in cells and becomes particularly relevant in highly complex cells such as neurons. An imbalance in mitochondrial dynamics can disrupt mitochondrial function, leading to abnormal cellular function and ultimately to a range of diseases, including neurodegenerative disorders.

HMGA1 stimulates cancer stem-like features and sensitivity to monensin in gastric cancer.

Gastric cancer represents a serious health problem worldwide, with insufficient molecular biomarkers and therapeutic options. Consequently, several efforts have been directed towards finding specific disease markers in order to develop new therapies capable of defeating gastric cancer. Attention has been pointed to cancer stem cells (CSCs) as they are primarily responsible for tumor initiation and recurrence, making them essential therapeutic targets.

Impact of Coffee Intake on Measures of Wellbeing in Mice.

Coffee intake is increasingly recognized as a life-style factor associated with the preservation of health, but there is still a debate on the relative effects of caffeinated and decaffeinated coffee. We now tested how the regular drinking of caffeinated and decaffeinated coffee for 3 weeks impacted on the behavior of male and female adult mice. Males drinking caffeinated coffee displayed statistically significant lower weight gain, increased sensorimotor coordination, greater motivation in the splash test, more struggling in the forced swimming test, faster onset of nest building, more marble burying and greater sociability.

Linking activation of synaptic NMDA receptors-induced CREB signaling to brief exposure of cortical neurons to oligomeric amyloid-beta peptide.

Amyloid-beta peptide oligomers (AβO) have been considered "primum movens" for a cascade of events that ultimately cause selective neuronal death in Alzheimer's disease (AD). However, initial events triggered by AβO have not been clearly defined. Synaptic (Syn) N-methyl-d-aspartate receptors (NMDAR) are known to activate cAMP response element-binding protein (CREB), a transcriptional factor involved in gene expression related to cell survival, memory formation and synaptic plasticity, whereas activation of extrasynaptic (ESyn) NMDARs was linked to excitotoxic events.

A combination of Δ-tetrahydrocannabinol and cannabidiol modulates glutamate dynamics in the hippocampus of an animal model of Alzheimer's disease.

A combination of Δ-tetrahydrocannabinol (Δ-THC) and cannabidiol (CBD) at non-psychoactive doses was previously demonstrated to reduce cognitive decline in APP/PS1 mice, an animal model of Alzheimer's disease (AD). However, the neurobiological substrates underlying these therapeutic properties of Δ-THC and CBD are not fully understood. Considering that dysregulation of glutamatergic activity contributes to cognitive impairment in AD, the present study evaluates the hypothesis that the combination of these two natural cannabinoids might reverse the alterations in glutamate dynamics within the hippocampus of this animal model of AD.

SNHG1: Redefining the Landscape of Hepatocellular Carcinoma through Long Noncoding RNAs.

Hepatocellular carcinoma (HCC) represents a global health concern, ranking as the sixth most common malignancy worldwide and the third leading cause of cancer-related mortality. Despite advances in research, the diagnosis and prognosis of such malignancy remain challenging. Alpha-fetoprotein, the current serum biomarker used in the management of HCC, has limited sensitivity and specificity, making early detection and effective management more difficult.

Design of experiment (DoE) of mucoadhesive valproic acid-loaded nanostructured lipid carriers (NLC) for potential nose-to-brain application.

Epilepsy is a highly prevalent neurological disease and valproic acid (VPA) is used as a first-line chronic treatment. However, this drug has poor oral bioavailability, which requires the administration of high doses, resulting in adverse effects. Alternative routes of VPA administration have therefore been investigated, such as the nose-to-brain route, which allows the drug to be transported directly from the nasal cavity to the brain.

Chronic Stress Alters Synaptic Inhibition/Excitation Balance of Pyramidal Neurons But Not PV Interneurons in the Infralimbic and Prelimbic Cortices of C57BL/6J Mice.

The medial prefrontal cortex (mPFC) plays a pivotal role in regulating working memory, executive function, and self-regulatory behaviors. Dysfunction in the mPFC circuits is a characteristic feature of several neuropsychiatric disorders including schizophrenia, depression, and post-traumatic stress disorder. Chronic stress (CS) is widely recognized as a major triggering factor for the onset of these disorders.

Identification and characterization of circulating and adipose tissue infiltrated CD20T cells from subjects with obesity that undergo bariatric surgery.

T cells play critical roles in adipose tissue (AT) inflammation. The role of CD20T cell in AT dysfunction and their contributing to insulin resistance (IR) and type 2 diabetes progression, is not known. The aim was to characterize CD20T cells in omental (OAT), subcutaneous (SAT) and peripheral blood (PB) from subjects with obesity (OB, n = 42), by flow cytometry.

Unveiling the antitumor mechanism of 7α-acetoxy-6β-hydroxyroyleanone from Plectranthus hadiensis in glioblastoma.

Ethnopharmacological Relevance: Glioblastoma (GB) is the most aggressive and prevalent glioma within the central nervous system. Despite considerable efforts, GB continues to exhibit a dismal 5-year survival rate (∼6%). This is largely attributed to unfavorable prognosis and lack of viable treatment options.