Engineering extracellular vesicles to transiently permeabilize the blood-brain barrier.

Background: Drug delivery to the brain is challenging due to the restrict permeability of the blood brain barrier (BBB). Recent studies indicate that BBB permeability increases over time during physiological aging likely due to factors (including extracellular vesicles (EVs)) that exist in the bloodstream. Therefore, inspiration can be taken from aging to develop new strategies for the transient opening of the BBB for drug delivery to the brain.

Combination of Gene Therapy and Chemotherapy in a New Targeted Hybrid Nanosystem to Hepatocellular Carcinoma.

Purpose: Hepatocellular carcinoma is the most frequent liver cancer and constitutes one of the main causes of cancer mortality. The combination of targeted therapy drugs, such as selumetinib and perifosine that inhibit cell signaling pathways involved in cell survival and proliferation, with the expression of tumor suppressor transgenes, such as PTEN, may result in an efficient therapeutic approach against HCC. Thus, the main objective of this work was to develop a new lipid-polymer hybrid nanosystem (HNP), composed of a PLGA core coated with a pH-sensitive lipid bilayer functionalized with the targeting ligand GalNAc, in order to specifically and efficiently deliver this novel combination of therapeutic agents in HCC cells.

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.

Creating Physiological Cell Environments In Vitro: Adjusting Cell Culture Media Composition and Oxygen Levels to Investigate Mitochondrial Function and Cancer Metabolism.

In vitro and ex vivo studies are crucial for mitochondrial research, offering valuable insights into cellular mechanisms and aiding in diagnostic and therapeutic strategies. Accurate in vitro models rely on adequate cell culture conditions, such as the composition of culture media and oxygenation levels. These conditions can influence energy metabolism and mitochondrial activities, thus impacting studies involving mitochondrial components, such as the effectiveness of anticancer drugs.

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.

Measurement of Mitochondrial ROS Formation.

Reactive oxygen species (ROS) play important roles in physiological and pathological processes. Mitochondria, particularly in skeletal and cardiac myocytes, are recognized as the primary site of ROS generation. Detecting oxidative modifications of intracellular or circulating molecules, such as lipids, proteins, and nucleic acids, is commonly employed to indicate ROS formation.

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.

Evaluation of Respiration with a Clark-Type Electrode in Isolated Mitochondria, Intact and Permeabilized Cells, and Explants from Animal Tissues.

Evaluation of mitochondrial function in aerobic cells is crucial for understanding the conditions that can potentially compromise their physiology. From the fields of Toxicology to Oncology, various approaches involving freshly isolated fractions of mitochondria, permeabilized cells, intact cells, or animal tissues have been employed to investigate metabolism through oxygen consumption.Several techniques are available for measuring oxygen consumption in liquids.

Leveraging Artificial Intelligence in GPCR Activation Studies: Computational Prediction Methods as Key Drivers of Knowledge.

G protein-coupled receptors (GPCRs) are key molecules involved in cellular signaling and are attractive targets for pharmacological intervention. This chapter is designed to explore the range of algorithms used to predict GPCRs' activation states, while also examining the pharmaceutical implications of these predictions. Our primary objective is to show how artificial intelligence (AI) is key in GPCR research to reveal the intricate dynamics of activation and inactivation processes, shedding light on the complex regulatory mechanisms of this vital protein family.

Age-associated metabolic and epigenetic barriers during direct reprogramming of mouse fibroblasts into induced cardiomyocytes.

Heart disease is the leading cause of mortality in developed countries, and novel regenerative procedures are warranted. Direct cardiac conversion (DCC) of adult fibroblasts can create induced cardiomyocytes (iCMs) for gene and cell-based heart therapy, and in addition to holding great promise, still lacks effectiveness as metabolic and age-associated barriers remain elusive. Here, by employing MGT (Mef2c, Gata4, Tbx5) transduction of mouse embryonic fibroblasts (MEFs) and adult (dermal and cardiac) fibroblasts from animals of different ages, we provide evidence that the direct reprogramming of fibroblasts into iCMs decreases with age.

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).

Peripheral immune profiling of soft tissue sarcoma: perspectives for disease monitoring.

Studying the tumor microenvironment and surrounding lymph nodes is the main focus of current immunological research on soft tissue sarcomas (STS). However, due to the restricted opportunity to examine tumor samples, alternative approaches are required to evaluate immune responses in non-surgical patients. Therefore, the purpose of this study was to evaluate the peripheral immune profile of STS patients, characterize patients accordingly and explore the impact of peripheral immunotypes on patient survival.

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.

Mannose and Lactobionic Acid in Nasal Vaccination: Enhancing Antigen Delivery via C-Type Lectin Receptors.

Background/objectives: Nasal vaccines are a promising strategy for enhancing mucosal immune responses and preventing diseases at mucosal sites by stimulating the secretion of secretory IgA, which is crucial for early pathogen neutralization. However, designing effective nasal vaccines is challenging due to the complex immunological mechanisms in the nasal mucosa, which must balance protection and tolerance against constant exposure to inhaled pathogens. The nasal route also presents unique formulation and delivery hurdles, such as the mucous layer hindering antigen penetration and immune cell access.

Predominance of as Agent of Dermatophytoses in Cape Verdean School-Age Children.

Dermatophytoses are infectious skin diseases of public health importance because of their transmissibility and high prevalence, especially among children. This is the first study aiming to estimate and report the burden of dermatophytoses on school-age children on the island of Santiago in Cape Verde, an African country that is an archipelago. A total of 249 students attending the afternoon shift of three elementary schools in the city of Achada Igreja were examined.

Gut-first Parkinson's disease is encoded by gut dysbiome.

Background: In Parkinson's patients, intestinal dysbiosis can occur years before clinical diagnosis, implicating the gut and its microbiota in the disease. Recent evidence suggests the gut microbiota may trigger body-first Parkinson Disease (PD), yet the underlying mechanisms remain unclear. This study aims to elucidate how a dysbiotic microbiome through intestinal immune alterations triggers PD-related neurodegeneration.

Functionalized Nanodiamonds for Targeted Neuronal Electromagnetic Signal Detection.

Intracellular sensing technologies necessitate a delicate balance of spatial resolution, sensitivity, biocompatibility, and stability. While existing methods partially fulfill these criteria, none offer a comprehensive solution. Nanodiamonds (NDs) harboring nitrogen-vacancy (NV) centers have emerged as promising candidates due to their sensing capabilities under biological conditions and their ability to meet all aforementioned requirements.