Gut microbiota dysbiosis affects intestinal sensitivity through epithelium-to-neuron signaling: novel insights from a colon organoid-based model to improve visceral pain therapy.

Chronic gastrointestinal pain is a hallmark of most intestinal pathologies, yet effective treatments remain elusive given the complexity of the underlying mechanisms. Aiming to investigate the intestinal epithelium contribution to visceral pain modulation in dysbiosis context, we first demonstrated that intracolonic instillation of microbe-free fecal supernatants from mice with post-inflammatory dysbiosis induced by dextran sodium sulfate (FS) provokes visceral hypersensitivity in recipient mice. Epithelium involvement in the response to FS was analyzed through a novel approach comprising murine epithelial colon organoids and primary dorsal root ganglia (DRG) neurons.

Bioactivity Assessment and Untargeted Metabolomics of the Mediterranean Sea Pen .

Octocorals have proven to be a prolific source of bioactive natural products, exhibiting a wide spectrum of pharmacological activities. Among octocorals, Pennatulaceans, commonly known as sea pens, are among the most dominant soft coral species living in benthic communities. Nonetheless, reports on bioactivity and chemical investigations of this genus are scarce.

Advances in Understanding the Molecular Dynamics of Autosomal Dominant Auditory Neuropathy: Unveiling a Novel DIAPH3 Gene Variant Associated With Sensorineural Hearing Loss and Bilateral Vestibular Aqueduct Enlargement.

Auditory neuropathy is characterized by abnormal neural conduction in the auditory pathway despite normal outer hair cell function, exhibiting substantial genetic heterogeneity and phenotypic variability. We report the case of a 29-year-old male patient with hearing loss, bilateral enlargement of the vestibular aqueduct (EVA), and vestibular system dysfunction. Based on these features, which are tipically indicative of Pendred syndrome, a molecular investigation including the SLC26A4 gene was performed.

The Role of microRNA-22 in Metabolism.

microRNA-22 (miR-22) plays a pivotal role in the regulation of metabolic processes and has emerged as a therapeutic target in metabolic disorders, including obesity, type 2 diabetes, and metabolic-associated liver diseases. While miR-22 exhibits context-dependent effects, promoting or inhibiting metabolic pathways depending on tissue and condition, current research highlights its therapeutic potential, particularly through inhibition strategies using chemically modified antisense oligonucleotides. This review examines the dual regulatory functions of miR-22 across key metabolic pathways, offering perspectives on its integration into next-generation diagnostic and therapeutic approaches while acknowledging the complexities of its roles in metabolic homeostasis.

Anti-Hyperalgesic Efficacy of Acetyl L-Carnitine (ALCAR) Against Visceral Pain Induced by Colitis: Involvement of Glia in the Enteric and Central Nervous System.

The management of abdominal pain in patients affected by inflammatory bowel diseases (IBDs) still represents a problem because of the lack of effective treatments. Acetyl L-carnitine (ALCAR) has proved useful in the treatment of different types of chronic pain with excellent tolerability. The present work aimed at evaluating the anti-hyperalgesic efficacy of ALCAR in a model of persistent visceral pain associated with colitis induced by 2,4-dinitrobenzene sulfonic acid (DNBS) injection.

Protective and Pain-Killer Effects of AMC3, a Novel N-Formyl Peptide Receptors (FPRs) Modulator, in Experimental Models of Rheumatoid Arthritis.

Rheumatoid arthritis is an autoimmune disorder that causes chronic joint pain, swelling, and movement impairment, resulting from prolonged inflammation-induced cartilage and bone degradation. The pathogenesis of RA, which is still unclear, makes diagnosis and treatment difficult and calls for new therapeutic strategies to cure the disease. Recent research has identified FPRs as a promising druggable target, with AMC3, a novel agonist, showing preclinical efficacy in vitro and in vivo.

Ultramicronized -Palmitoylethanolamine Regulates Mast Cell-Astrocyte Crosstalk: A New Potential Mechanism Underlying the Inhibition of Morphine Tolerance.

Persistent pain can be managed with opioids, but their use is limited by the onset of tolerance. Ultramicronized -palmitoylethanolamine (PEA) in vivo delays morphine tolerance with mechanisms that are still unclear. Since glial cells are involved in opioid tolerance and mast cells (MCs) are pivotal targets of PEA, we hypothesized that a potential mechanism by which PEA delays opioid tolerance might depend on the control of the crosstalk between these cells.

-Derived Conotoxins: Novel Therapeutic Opportunities from a Marine Organism.

is a marine venomous mollusk of the genus that captures its prey by injecting a rich cocktail of bioactive disulfide bond rich peptides called conotoxins. These peptides selectively target a broad range of ion channels, membrane receptors, transporters, and enzymes, making them valuable pharmacological tools and potential drug leads. -derived conotoxins are particularly attractive due to their marked potency and selectivity against specific nicotinic acetylcholine receptor subtypes, whose signalling is involved in pain, cognitive disorders, drug addiction, and cancer.

The Efficacy of Defatted Seed Meal against Colitis-Induced Persistent Visceral Hypersensitivity: The Relevance of PPAR α Receptor Activation in Pain Relief.

are natural sources of bioactive compounds able to promote gut health. Belonging to this plant family, is an ancient oil crop rich in glucosinolates, polyunsaturated fatty acids, and antioxidants that is attracting renewed attention for its nutraceutical potential. This work aimed at investigating the therapeutic effects of a defatted seed meal (DSM) of on the colon damage and the persistent visceral hypersensitivity associated with colitis in rats.

Inhibitors of Mitochondrial Human Carbonic Anhydrases VA and VB as a Therapeutic Strategy against Paclitaxel-Induced Neuropathic Pain in Mice.

Neuropathy development is a major dose-limiting side effect of anticancer treatments that significantly reduces patient's quality of life. The inadequate pharmacological approaches for neuropathic pain management warrant the identification of novel therapeutic targets. Mitochondrial dysfunctions that lead to reactive oxygen species (ROS) increase, cytosolic Ca imbalance, and lactate acidosis are implicated in neuropathic pain pathogenesis.

Effectiveness of selective neck dissection in head and neck cancer: the experience of two Italian centers.

Objective: The aim of this study was to evaluate the oncologic outcomes after a selective neck dissection (SND), both in elective and therapeutic settings, with particular regard to regional recurrence rate.

Methods: Retrospective analysis of 827 patients with head and neck primary tumors submitted to SND from 1999 to 2011 in two large hospital centers of northern Italy.

Results: A total of 40 neck recurrences were found in the whole series, with the same incidence after primary or salvage surgery (4.