Actionable NSCLC Mutation Identification by Comprehensive Genomic Profiling for Clinical Trial Enrollment: The European Program for the Routine Testing of Patients With Advanced Lung Cancer (EPROPA).

Introduction: The advocacy Women Against Lung Cancer in Europe (WALCE) promoted the European Program for the Routine Testing of Patients With Advanced Lung Cancer (EPROPA) and provided a free-of-charge molecular profiling platform for NSCLC sample characterization with the aim of increasing the detection of targetable drivers and improving patients' access to clinical trials in Europe.

Methods: From January 2021 to December 2023, 20 centers located at five different European countries (Greece, Slovenia, Romania, Albania, and Italy) joined EPROPA, with 555 patients with advanced NSCLC registered to the program. Anonymized patients' clinical-pathological data were shared through the EPROPA web platform and tissue samples were collected at the Molecular Pathology Unit of the Reference Center (University of Turin) for molecular analyses.

Aldehyde dehydrogenase-2 deficiency aggravates neuroinflammation, nociception, and motor impairment in a mouse model of multiple sclerosis.

Aldehyde dehydrogenase-2 deficiency (ALDH2∗2) found in 36 % of Han Chinese, affects approximately 8 % of the world population. ALDH2 is a mitochondrial key enzyme in detoxifying reactive aldehydes to less reactive forms. Studies demonstrate a potential link between ALDH2∗2 mutation and neurodegenerative diseases.

Pulmonary Low Malignant Potential Adenocarcinoma: A Validation of the Proposed Criteria for This Novel Subtype.

Adenocarcinoma (ADC) is the most common histologic type of lung cancer, including in situ (lepidic), minimally invasive, and invasive forms. While the former 2 types are associated with a favorable outcome, the latter includes tumors with variable behavior, often tumor stage-related. A recent study proposed strict morphologic criteria defining a new subgroup of resected stage I invasive ADC (16% of cases) with favorable outcomes (100% disease-specific survival), named "ADC of low malignant potential (LMP-ADC).

4-Hydroxynonenal impairs miRNA maturation in heart failure via Dicer post-translational modification.

Background And Aims: Developing novel therapies to battle the global public health burden of heart failure remains challenging. This study investigates the underlying mechanisms and potential treatment for 4-hydroxynonenal (4-HNE) deleterious effects in heart failure.

Methods: Biochemical, functional, and histochemical measurements were applied to identify 4-HNE adducts in rat and human failing hearts.

Wnt signaling is involved in crotalphine-induced analgesia in a rat model of neuropathic pain.

The aberrant activation of Wnt/β-catenin and atypical Wnt/Ryk signaling pathways in the spinal cord is critical for the development and maintenance of neuropathic pain. Crotalphine is a structural analog to a peptide first identified in Crotalus durissus terrificus snake venom, which induces antinociception by activating kappa-opioid and CB cannabinoid receptors. Consistent with previous data, we showed that the protein levels of the canonical Wnt/β-catenin and the atypical Wnt/Ryk signaling pathways are increased in neuropathic rats.

Exploring circular MET RNA as a potential biomarker in tumors exhibiting high MET activity.

Background: MET-driven acquired resistance is emerging with unanticipated frequency in patients relapsing upon molecular therapy treatments. However, the determination of MET amplification remains challenging using both standard and next-generation sequencing-based methodologies. Liquid biopsy is an effective, non-invasive approach to define cancer genomic profiles, track tumor evolution over time, monitor treatment response and detect molecular resistance in advance.

Treatment with levosimendan in an experimental model of early ventilator-induced diaphragmatic dysfunction.

Introduction: Mechanical ventilation (MV) is a life-saving approach in critically ill patients. However, it may affect the diaphragmatic structure and function, beyond the lungs. Levosimendan is a calcium sensitizer widely used in clinics to improve cardiac contractility in acute heart failure patients.

A human TRPV1 genetic variant within the channel gating domain regulates pain sensitivity in rodents.

Pain signals are relayed to the brain via a nociceptive system, and in rare cases, this nociceptive system contains genetic variants that can limit the pain response. Here, we questioned whether a human transient receptor potential vanilloid 1 (TRPV1) missense variant causes a resistance to noxious stimuli and, further, whether we could target this region with a cell-permeable peptide as a pain therapeutic. Initially using a computational approach, we identified a human K710N TRPV1 missense variant in an otherwise highly conserved region of mammalian TRPV1.

Formyl peptide receptors are involved in CTX-induced impairment of lymphocyte functions.

Crotoxin (CTX) is a neurotoxin that is isolated from the venom of Crotalus durissus terrificus, which displays immunomodulatory, anti-inflammatory, and anti-tumoral effects. Previous research has demonstrated that CTX promotes the adherence of leukocytes to the endothelial cells in blood microcirculation and the high endothelial venules of lymph nodes, which reduces the number of blood cells and lymphocytes. Studies have also shown that these effects are mediated by lipoxygenase-derived mediators.

TEGDMA-Functionalized Dicalcium Phosphate Dihydrate Resin-Based Composites Prevent Secondary Caries in an In Vitro Biofilm Model.

This study evaluated the efficacy of experimental TEGDMA-functionalized dicalcium phosphate dihydrate (T-DCPD) filler-based resin-based composites (RBC) in preventing caries lesions around the restoration margins (secondary caries, SC). Standardized Class-II cavities were made in sound molars with the cervical margin in dentin. Cavities were filled with a commercial resin-modified glass-ionomer cement (RMGIC) or experimental RBCs containing a bisGMA-TEGDMA resin blend and one of the following inorganic fractions: 60 wt.

Caspase-1 and Cathepsin B Inhibitors from Marine Invertebrates, Aiming at a Reduction in Neuroinflammation.

Neuroinflammation is a condition associated with several types of dementia, such as Alzheimer's disease (AD), mainly caused by an inflammatory response to amyloid peptides that induce microglial activation, with subsequent cytokine release. Neuronal caspase-1 from inflammasome and cathepsin B are key enzymes mediating neuroinflammation in AD, therefore, revealing new molecules to modulate these enzymes may be an interesting approach to treat neurodegenerative diseases. In this study, we searched for new caspase-1 and cathepsin B inhibitors from five species of Brazilian marine invertebrates (four cnidarians and one echinoderm).

Microbiological models for accelerated development of secondary caries in vitro.

Objectives: The current study aimed to compare the efficacy of two in vitro microbiological models based on open and closed systems designed to obtain secondary caries in an accelerated and reproducible way.

Methods: A conventional resin-based composite (RBC - Majesty ES-2; Kuraray, Japan) and a resin-modified glass-ionomer cement (RMGIC - Ionolux; VOCO, Germany) were used to restore standardized class II cavities (n = 4/tooth, cervical margin in dentin) in 16 human molars. The ability to produce secondary caries with Streptococcus mutans biofilms was tested using either an open-cycle or closed-cycle bioreactor (n = 8 specimens/model).

Crotalphine Modulates Microglia M1/M2 Phenotypes and Induces Spinal Analgesia Mediated by Opioid-Cannabinoid Systems.

Pain is a worldwide public health problem and its treatment is still a challenge since clinically available drugs do not completely reverse chronic painful states or induce undesirable effects. Crotalphine is a 14 amino acids synthetic peptide that induces a potent and long-lasting analgesic effect on acute and chronic pain models, peripherally mediated by the endogenous release of dynorphin A and the desensitization of the transient receptor potential ankyrin 1 (TRPA1) receptor. However, the effects of crotalphine on the central nervous system (CNS) and the signaling pathway have not been investigated.

Activation of PKCε-ALDH2 Axis Prevents 4-HNE-Induced Pain in Mice.

Protein kinase Cε (PKCε) is highly expressed in nociceptor neurons and its activation has been reported as pro-nociceptive. Intriguingly, we previously demonstrated that activation of the mitochondrial PKCε substrate aldehyde dehydrogenase-2 (ALDH2) results in anti-nociceptive effects. ALDH2 is a major enzyme responsible for the clearance of 4-hydroxy-2-nonenal (4-HNE), an oxidative stress byproduct accumulated in inflammatory conditions and sufficient to induce pain hypersensitivity in rodents.