Decoding Urinary Tract Infection Trends: A 5-Year Snapshot from Central Portugal.

Introduction: This study analyzes urinary tract infections (UTIs) in a hospital in Central Portugal over a five-year period, focusing on bacterial prevalence, patient demographics, and antibiotic resistance patterns. This investigation aims to provide insights that can guide improved infection control and treatment strategies.

Methods: A total of 6161 positive urine cultures collected over five years were examined, with particular emphasis on 2019 due to a peak in infection rates.

GPCR oligomerization across classes: A2AR-mediated regulation of mGlu5R activation.

The adenosine A receptor (AR), a class A GPCR, is a known player in neurological diseases, including Parkinson's disease and Alzheimer's disease, and is also implicated in SARS-CoV-2 infection. Recent studies have revealed its oligomerization with metabotropic glutamate receptor type 5 (mGluR), a class C G protein coupled receptor (GPCR) that exists in the homodimeric form. Simultaneous activation of both receptors synergistically enhances mGluR-mediated effects in the hippocampus.

Dendritic cells in triple-negative breast cancer: From pathophysiology to therapeutic applications.

Breast cancer is the second most commonly diagnosed cancer in women and the fifth leading cause of cancer-related deaths worldwide. It is a highly heterogeneous disease, consisting of multiple subtypes that vary significantly in clinical characteristics and survival outcomes. Triple-negative breast cancer (TNBC) is a particularly aggressive and challenging subtype of breast cancer.

The (un)known crosstalk between metabolism and mechanotransduction: Implications for metabolic syndrome (MetS)-associated neurological complications.

Metabolic syndrome (MetS) has been associated with disruptions in tissue mechanical homeostasis and inflammatory and metabolic derangements. However, the direct correlation between metabolic alterations and changes in tissue stiffness, and whether they could play a role as upstream initiators of disease pathology remains to be investigated. This emerging concept has yet to be put into clinical practice as many questions concerning the interplay between extracellular matrix mechanical properties and regulation of metabolic pathways remain unsolved.

Impact of Nutrition on the Gut Microbiota: Implications for Parkinson's Disease.

Parkinson's disease (PD) is a multifactorial neurodegenerative disease that is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta and by the anomalous accumulation of α-synuclein aggregates into Lewy bodies and Lewy neurites. Research suggests 2 distinct subtypes of PD: the brain-first subtype if the pathology arises from the brain and then spreads to the peripheral nervous system (PNS) and the body-first subtype, where the pathological process begins in the PNS and then spreads to the central nervous system. This review primarily focuses on the body-first subtype.

Glia: The Cellular Glue that binds Circadian Rhythms and Sleep.

Glia are increasingly appreciated as serving an important function in the control of sleep and circadian rhythms. Glial cells in Drosophila and mammals regulate daily rhythms of locomotor activity and sleep as well as homeostatic rebound following sleep deprivation. In addition, they contribute to proposed functions of sleep, with different functions mapping to varied glial subtypes.

Cryogenic, but not hypothermic, preservation disrupts the extracellular matrix of cell sheets.

Cell sheet (CS)-based approaches hold significant potential for tissue regeneration, relying on the extracellular matrix (ECM) for success. Like in native tissues, the ECM provides structural and biochemical support for cellular homeostasis and function. Effective preservation strategies that maintain ECM integrity are critical to enhance the therapeutic potential of CS-based approaches.

Clove Essential Oil as a Source of Antitumoral Compounds Capable of Crossing the Blood-Brain Barrier: A Focus on the Effects of β-Caryophyllene and Eugenol in a Glioblastoma Cell Line.

This study aimed to investigate β-Caryophyllene (BCA) pharmacokinetics as well as the potential antitumor activity and mechanism of action of BCA and eugenol (EU), alone or in combination, in U87 glioblastoma (GB) cells. The BCA pharmacokinetic was studied by evaluating its concentration profiles in rat blood and cerebrospinal fluid after oral and intravenous administration. EU and BCA antitumor mechanisms were assessed by comparing their effects in U87 GB cells and non-tumoral HMC3 cells.

The mitochondriotropic antioxidants AntiOxBEN and AntiOxCIN are structurally-similar but differentially alter energy homeostasis in human skin fibroblasts.

Mitochondrial dysfunction and increased reactive oxygen species (ROS) generation play an import role in different human pathologies. In this context, mitochondrial targeting of potentially protective antioxidants by their coupling to the lipophilic triphenylphosphonium cation (TPP) is widely applied. Employing a six‑carbon (C) linker, we recently demonstrated that mitochondria-targeted phenolic antioxidants derived from gallic acid (AntiOxBEN) and caffeic acid (AntiOxCIN) counterbalance oxidative stress in primary human skin fibroblasts by activating ROS-protective mechanisms.

Comparing adenosine A receptor modulation of cannabinoid CB receptor-mediated inhibition of GABA and glutamate release in rodent striatal nerve terminals.

In corticostriatal nerve terminals, glutamate release is stimulated by adenosine via A receptors (ARs) and simultaneously inhibited by endocannabinoids via CB receptors (CBRs). We previously identified presynaptic AR-CBR heterotetrameric complexes in corticostriatal nerve terminals. We now explored the possible functional interaction between ARs and CBRs in purified striatal GABAergic nerve terminals (synaptosomes) and compared these findings with those on the release of glutamate.

Design, Synthesis, and Biological Evaluation of Novel Urea-Containing Carnosic Acid Derivatives with Anticancer Activity.

A series of novel carnosic acid derivatives incorporating urea moieties at the C-20 position was synthesized and evaluated for their antiproliferative activity against the HCT116 colorectal cancer cell line. Most derivatives demonstrated enhanced antiproliferative activity compared to that of carnosic acid . The most promising derivatives were tested in other colorectal cancer cell lines (SW480, SW620, and Caco-2), melanoma (A375), and pancreatic cancer (MiaPaca-2).

High percentage of immune Th1 and Tc1 cells infiltrating visceral adipose tissue in people with obesity.

Subcutaneous (SAT) and visceral (VAT) adipose tissue dysfunction during the obesity onset can lead to increased expression of inflammatory molecules, and consequently to immune cell infiltration. The aim was to deeply characterize the T cells, those infiltrating SAT and VAT, compared to peripheral blood (PB), in individuals undergoing bariatric surgery. Forty-two adult individuals were recruited, SAT and VAT samples were collected.

HepG2 spheroids cultured in alginate microcapsules as a model for exploring mitochondrial and glycolytic metabolism using the Seahorse XFe24 Analyzer.

Mitochondria are affected by chemical substances and play a critical role in drug-induced liver injury (DILI). Chemical substances can have a significant impact on various cellular processes, such as the disruption of oxidative phosphorylation, oxidative stress, and alteration of glucose metabolism. Given the consequences of these effects, it is crucial to understand the molecular pathways of chemical substances in the context of hepatotoxicity to prevent and treat DILI.

Transcription factor-mediated reprogramming to antigen-presenting cells.

Antigen-presenting cells (APCs) are a heterogenous group of immune cells composed by dendritic cells (DCs) and macrophages (Mϕ), which are critical for orchestrating immunity against cancer or infections. Several strategies have been explored to generate APC subsets, including enrichment from peripheral blood and differentiation from pluripotent or multipotent cells. During development, the generation of APC subsets is instructed by transcription factors (TFs).

Ferroptosis driven by nanoparticles for tackling glioblastoma.

Glioblastoma (GBM) is the most aggressive, malignant, and drug-resistant brain tumor. There are no effective treatment options for GBM, which usually leads to relapses that cause patients to die a few months later. Ferroptosis, a newly discovered mechanism of regulated cell death, has been identified as a tumor suppressor in solid tumors and represents an alternative to apoptosis resistance.

Early-life IL-4 administration induces long-term changes in microglia in the cerebellum and prefrontal cortex.

Microglia are crucial for brain development and their function can be impacted by postnatal insults, such as early-life allergies. These are characterized by an upregulation of interleukin (IL)-4 levels. Allergies share a strong comorbidity with Autism Spectrum Disorders (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD).

Regional distribution of polymorphisms associated to the disease-causing gene of spinocerebellar ataxia type 3.

Introduction: Knowledge about the distribution and frequency of the respective haplotypes on the wildtype and mutant allele is highly relevant in the context of future gene therapy clinical studies in Spinocerebellar Ataxia Type 3, the most common autosomal dominantly inherited ataxia. Single nucleotide polymorphisms associated to the disease-causing gene, ATXN3, have been determined. We wanted to investigate the frequency and regional distribution of two intragenic single nucleotide polymorphisms (SNPs) in a large European SCA3 cohort and their relation to the clinical phenotype.

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.