Clavulanic acid prevents paclitaxel-induced neuropathic pain through a systemic and central anti-inflammatory effect in mice.

Paclitaxel (PCX) based treatments, commonly used to treat breast, ovarian and lung cancers, have the highest incidence of chemotherapy-induced neuropathic pain, affecting from 38 to 94 ​% of patients. Unfortunately, analgesic treatments are not always effective for PCX-induced neuropathic pain (PINP). This study aimed to evaluate the antinociceptive effect of clavulanic acid (CLAV), a clinically used β-lactam molecule, in both therapeutic and preventive contexts in mice with PINP.

Hypothalamic cerebrospinal fluid-contacting neurons project to the rostral agranular insular cortex: An immunofluorescence and ultrastructural analysis in the rat.

Cerebrospinal fluid-contacting neurons (CSF-cNS) are considered mechanoreceptors and chemoreceptors involved in detecting changes in CSF circulation. However, considering that recent data suggest that this type of cell could exert an active response when an external stimulus is sensed, identification of CSF-cNS may be relevant. In this regard, some data suggest that a neuronal connection exists between the ventral region of the hypothalamic paraventricular nucleus (PVN) and rostral agranular insular cortex (RAIC); indeed, a potential CSF-cNS is hypothesized.

Design, manufacturing and experimental validation of additive manufacturing cores for bearing seats in carbon fibre reinforced polymer structures.

The integration of carbon-fibre reinforced polymers (CFRP) in structural applications offers significant advantages due to their high strength-to-weight ratio. However, these materials exhibit limitations under out-of-plane loads, particularly in bearing applications. This study explores an innovative approach to enhance the performance of CFRP structures in such scenarios by incorporating annular polyamide inserts manufactured via additive manufacturing (AM).

Effect of non-thermal acidic and alkaline modifications on the structural, pasting, rheological, and functional properties of cassava (Manihot esculenta) starch.

This study aimed to investigate the effects of acid or alkali modification of isolated cassava starch (ICS) on its physicochemical properties. Acetic acid concentrations of 5%, 10%, and 20% v/v (0.87, 1.

Dysarthria-clumsy hand syndrome and multiple sequential acute limb embolisms as a form of presentation of aortic arch embolism.

Introduction: Aortic arch complex atheromatosis is a source of cerebral embolism. A percentage of lacunar infarct could be of embolic etiology, especially due to microemboli of the aortic arch.

Case Report: We present the case of a 63-year-old hypertensive man suffering from dysarthria-clumsy hand syndrome for a right hemispheric minor ischemic stroke.

The Dual Role of Antimicrobial Proteins and Peptides: Exploring Their Direct Impact and Plant Defense-Enhancing Abilities.

Plants face numerous environmental stresses that hinder their growth and productivity, including biotic agents, such as herbivores and parasitic microorganisms, as well as abiotic factors, such as cold, drought, salinity, and high temperature. To counter these challenges, plants have developed a range of defense strategies. Among these, plant antimicrobial proteins and peptides (APPs) have emerged as a promising solution.

Structural basis of positive allosteric modulation of metabotropic glutamate receptor activation and internalization.

The metabotropic glutamate receptors (mGluRs) are neuromodulatory family C G protein coupled receptors which assemble as dimers and allosterically couple extracellular ligand binding domains (LBDs) to transmembrane domains (TMDs) to drive intracellular signaling. Pharmacologically, mGluRs can be targeted at the LBDs by glutamate and synthetic orthosteric compounds or at the TMDs by allosteric modulators. Despite the potential of allosteric compounds as therapeutics, an understanding of the functional and structural basis of their effects is limited.

Control of G protein-coupled receptor function via membrane-interacting intrinsically disordered C-terminal domains.

G protein-coupled receptors (GPCRs) control intracellular signaling cascades via agonist-dependent coupling to intracellular transducers including heterotrimeric G proteins, GPCR kinases (GRKs), and arrestins. In addition to their critical interactions with the transmembrane core of active GPCRs, all three classes of transducers have also been reported to interact with receptor C-terminal domains (CTDs). An underexplored aspect of GPCR CTDs is their possible role as lipid sensors given their proximity to the membrane.

Enhancing Concrete Durability and Strength with Fly Ash, Steel Slag, and Rice Husk Ash for Marine Environments.

The effect of an alternative source of silica, based on class F fly ash mixed with blast furnace slag and activated by rice husk ash (RHA), to produce concrete exposed to marine environments was evaluated. Four mixtures activated by the combination of 85% NaOH 14M + 15% RHA were manufactured to achieve a liquid/solid ratio of 0.20.

Deuteration as a General Strategy to Enhance Azobenzene-Based Photopharmacology.

Chemical photoswitches have become a widely used approach for the remote control of biological functions with spatiotemporal precision. Several molecular scaffolds have been implemented to improve photoswitch characteristics, ranging from the nature of the photoswitch itself (e.g.

Emerging modes of regulation of neuromodulatory G protein-coupled receptors.

In the nervous system, G protein-coupled receptors (GPCRs) control neuronal excitability, synaptic transmission, synaptic plasticity, and, ultimately, behavior through spatiotemporally precise initiation of a variety of signaling pathways. However, despite their critical importance, there is incomplete understanding of how these receptors are regulated to tune their signaling to specific neurophysiological contexts. A deeper mechanistic picture of neuromodulatory GPCR function is needed to fully decipher their biological roles and effectively harness them for the treatment of neurological and psychiatric disorders.

Brain health in diverse settings: How age, demographics and cognition shape brain function.

Diversity in brain health is influenced by individual differences in demographics and cognition. However, most studies on brain health and diseases have typically controlled for these factors rather than explored their potential to predict brain signals. Here, we assessed the role of individual differences in demographics (age, sex, and education; n = 1298) and cognition (n = 725) as predictors of different metrics usually used in case-control studies.

Novel Blood Biomarkers for Response Prediction and Monitoring of Stereotactic Ablative Radiotherapy and Immunotherapy in Metastatic Oligoprogressive Lung Cancer.

Up to 80% of patients under immune checkpoint inhibitors (ICI) face resistance. In this context, stereotactic ablative radiotherapy (SABR) can induce an immune or abscopal response. However, its molecular determinants remain unknown.

Profiling the proximal proteome of the activated μ-opioid receptor.

The μ-opioid receptor (μOR) represents an important target of therapeutic and abused drugs. So far, most understanding of μOR activity has focused on a subset of known signal transducers and regulatory molecules. Yet μOR signaling is coordinated by additional proteins in the interaction network of the activated receptor, which have largely remained invisible given the lack of technologies to interrogate these networks systematically.

Hypothalamic Paraventricular Stimulation Inhibits Nociceptive Wide Dynamic Range Trigeminocervical Complex Cells via Oxytocinergic Transmission.

Oxytocinergic transmission blocks nociception at the peripheral, spinal, and supraspinal levels through the oxytocin receptor (OTR). Indeed, a neuronal pathway from the hypothalamic paraventricular nucleus (PVN) to the spinal cord and trigeminal nucleus caudalis (Sp5c) has been described. Hence, although the trigeminocervical complex (TCC), an anatomical area spanning the Sp5c, C1, and C2 regions, plays a role in some pain disorders associated with craniofacial structures (e.

Evidence of validity and reliability of the Colombian version of Addenbroke's Cognitive Examination Revised (ACE-R).

Objective: The purpose of this study is to provide evidence that supports the validity and reliability of the Colombian version of the Addenbrooke's Cognitive Examination Revised (ACE-R) in comparison to the MMSE at assessing and finding patients with Mild Cognitive Impairment (MCI). Additionally, the study aims to determine the optimal cut-off scores based on the age of a population with a low education level.

Method: This study included 314 individuals (235 participants diagnosed with MCI and 79 cognitively healthy) who live in two different rural departments (states) in Colombia.

Prevalence of Mild Cognitive Impairment in Southern Regions of Colombia.

Background: Recent reports suggest that by 2050 there will be an increase of around 310% of cases affected by dementia in Latin American countries. A previous study in a Southern region reported one of the highest prevalences of dementia in Latin America.

Objective: To investigate the prevalence of mild cognitive impairment associated with low education, rurality, and demographic characteristics.

Distinct beta-arrestin coupling and intracellular trafficking of metabotropic glutamate receptor homo- and heterodimers.

The metabotropic glutamate receptors (mGluRs) are family C, dimeric G protein-coupled receptors (GPCRs), which play critical roles in synaptic transmission. Despite an increasing appreciation of the molecular diversity of this family, how distinct mGluR subtypes are regulated remains poorly understood. We reveal that different group II/III mGluR subtypes show markedly different beta-arrestin (β-arr) coupling and endocytic trafficking.

Clavulanic Acid and its Potential Therapeutic Effects on the Central Nervous System.

Clavulanic acid (CLAV) is a non-antibiotic β-lactam that has been used since the late 1970s as a β-lactamase inhibitor in combination with amoxicillin, another ß-lactam with antibiotic activity. Its long-observed adverse reaction profile allows it to say that CLAV is a well-tolerated drug with mainly mild adverse reactions. Interestingly, in 2005, it was discovered that β-lactams enhance the astrocytic expression of GLT-1, a glutamate transporter essential for maintaining synaptic glutamate homeostasis involved in several pathologies of the central nervous system (CNS).

Analysis of ANRIL Isoforms and Key Genes in Patients with Severe Coronary Artery Disease.

ANRIL (Antisense Noncoding RNA in the INK4 Locus), also named CDKN2B-AS1, is a long non-coding RNA with outstanding functions that regulates genes involved in atherosclerosis development. ANRIL genotypes and the expression of linear and circular isoforms have been associated with coronary artery disease (CAD). The CDKN2A and the CDKN2B genes at the CDKN2A/B locus encode the Cyclin-Dependent Kinase inhibitor protein (CDKI) p16INK4a and the p53 regulatory protein p14ARF, which are involved in cell cycle regulation, aging, senescence, and apoptosis.