Background: Interleukin-2 (IL-2) is a pivotal cytokine that regulates T cell activation, proliferation, and survival, and plays a central role in shaping adaptive immune responses. Modulation of IL-2 production has therefore been considered an important strategy for enhancing immune function in various disease settings, including cancer and immunodeficiency. Recent advances in drug repurposing have highlighted the potential of FDA-approved compounds as novel immunomodulatory agents with well-characterized safety profiles. In this study, we screened an FDA-approved drug library and identified the PARP inhibitor rucaparib as a compound that enhances IL-2 production in EL-4 T cells and splenocytes. Results: Rucaparib significantly increased IL-2 production in murine EL-4 T cells under both unstimulated conditions and following activation with Phorbol 12-myristate 13-acetate (PMA) and ionomycin (Io), without affecting cell viability. In primary mouse splenocytes, rucaparib enhanced IL-2 production under concanavalin A (ConA) stimulation and increased tumor necrosis factor-α (TNF-α) production in response to lipopolysaccharide (LPS), with no detectable cytotoxicity. In vivo, BALB/c mice administered rucaparib (5 or 10 mg/kg) for one week showed no cytotoxic effects in isolated splenocytes under either basal or mitogen-stimulated conditions. Mechanistically, rucaparib enhanced IL-2 and NF-κB promoter activities in PMA/Io stimulated EL-4 T cells, indicating transcriptional activation of T cell signaling pathways. Conclusion: Rucaparib enhances cytokine production and transcriptional activation in immune cells without inducing cytotoxicity, suggesting its potential as a modulator of T cell-mediated immune responses.
Quercetin, a dietary flavonoid, contributes to bowel regulation and anti-inflammatory effects. Enterochromaffin (EC) cells express transient receptor potential ankyrin1 (TRPA1) and significantly contribute to gastrointestinal motility and secretion via 5-hydroxytryptamine (5-HT) release. A recent study reported that flavonoids, including quercetin, activate heterogeneously expressed TRPA1. We here evaluated the effects of quercetin and its analogs (kaempferol and galangin) on TRPA1 channels using RIN-14B, an EC model cell line. To elucidate the function of these flavonoids, intracellular Ca2+ concentration ([Ca2+]i) was measured, and 5-HT release from RIN-14B cells was analyzed. Quercetin- and kaempferol-induced [Ca2+]i increases, which were abolished by extracellular Ca2+ removal. The [Ca2+]i responses to quercetin and kaempferol were partially suppressed by TRPA1 antagonists and nearly completely abolished by L-type voltage-dependent Ca2+ (Cav) channel inhibitors. Reverse transcription-polymerase chain reaction analysis confirmed the expression of both TRPA1 and L-type Cav channels in RIN-14B cells. Quercetin- and kaempferol-induced 5-HT release from RIN-14B cells was inhibited by TRPA1 antagonists and L-type Cav channel inhibitors. Along with the activation effects, flavonoids inhibited the [Ca2+]i responses to TRPA1 agonists, with the inhibitory potency ranking as follows: quercetin, kaempferol, and galangin. Moreover, these flavonoids demonstrated inhibitory effects on heterogeneously expressed TRPA1. Furthermore, flavonoids inhibited TRPA1 agonist-induced 5-HT release from RIN-14B cells. These results suggest that flavonoids can regulate 5-HT secretion through TRPA1 and L-type Cav channels. Dietary flavonoids may hold therapeutic potential for gastrointestinal functions and disorders.
The growing challenge of antimicrobial resistance has necessitated the development of new antibiotics with novel mechanisms of action. Gepotidacin is a first-in-class triazaacenaphthylene antibiotic developed for the treatment of uncomplicated urinary tract infections (uUTIs) in female adults and adolescents. It inhibits bacterial DNA replication by targeting both DNA gyrase and topoisomerase IV at a distinct binding site, differing from fluoroquinolones and therefore presenting a novel mechanism of action. However, resistance-associated mutations affecting susceptibility have been documented, emphasizing the need for ongoing monitoring. Pharmacokinetic studies indicate predictable, dose-dependent oral absorption suitable for twice- or thrice-daily dosing, with minimal accumulation and comparable profiles across populations. In terms of therapeutic success for the treatment of uUTIs, phase III clinical trials (EAGLE-2 and EAGLE-3) have demonstrated that gepotidacin was non‑inferior to the broad-spectrum antibiotic nitrofurantoin in EAGLE-2 and even superior to nitrofurantoin in EAGLE-3, with a tolerability profile comparable to other antibiotics of its class. Studies also suggest potential efficacy against uncomplicated gonorrhea (GC), including strains resistant to current therapies. Adverse events were generally mild to moderate, predominantly gastrointestinal, and caution is advised in patients with QT prolongation risk. While gepotidacin represents an important addition to the limited pool of oral antibiotics for these infections, its long-term clinical utility will depend on careful stewardship, resistance surveillance, and further evaluation in broader indications and combination regimens.
Ex vivo lung perfusion (EVLP) is now an established normothermic machine-perfusion strategy in lung transplantation, primarily enabling structured donor lung assessment, short-term preservation, and selective rehabilitation outside the recipient. Because the supply of transplantable lungs remains limited, clinically implemented EVLP protocols have increased donor-lung utilization by allowing transplant teams to evaluate marginal grafts under near-physiological ventilation and perfusion rather than relying exclusively on static cold storage. The perfusate is central to this process because it stabilizes colloid osmotic pressure, electrolytes, buffering capacity, metabolic substrates, and oxygen transport according to protocol requirements. This review critically summarizes the development of EVLP perfusates and separates clinically validated roles from experimental repair strategies. We first distinguish EVLP perfusates from cold preservation solutions and compare acellular, red blood cell-containing, and whole-blood approaches with attention to their physiological rationale, logistical constraints, and level of evidence. We then discuss protocol-specific additives, including anti-inflammatory agents, antioxidants, antimicrobials, anticoagulants, hormones, nutritional substrates, and cellular or gene-based therapies. Emerging interventions such as polymerized hemoglobin, cytokine adsorption, mesenchymal stromal cell-derived products, CRISPR-Cas-mediated interleukin-10 modulation, and prolonged or intermittent EVLP illustrate the expanding therapeutic potential of the platform. However, most of these strategies remain preclinical or early translational. Future perfusate development should therefore prioritize standardized outcome measures, evidence-based component selection, and careful separation of organ preservation, organ assessment, and organ rehabilitation.
BACKGROUND:Antimicrobial resistance (AMR) is one of the most pressing global health problems, resulting from the misuse and overuse of antibiotics across various sectors, which has led to the emergence and spread of resistant microorganisms. AMR occurs when microorganisms no longer respond to antibiotics. In Italy alone, AMR is responsible for over 10,000 deaths each year, exceeding 40% of all AMR, attributable deaths in the EU/EEA. This alarming trend highlights the urgent need to preserve effective treatment options and to re-evaluate the role of well-established oral antibiotics with a favourable pharmacological and microbiological profile. SUMMARY:Ceftibuten is an oral third-generation cephalosporin with potent activity against many Gram-negative and some Gram-positive pathogens, including several Gram-negative pathogens. It is approved for the treatment of respiratory and urinary tract infections, both uncomplicated and complicated, in adults as well as in children. This review discusses clinical and pharmacological data supporting ceftibuten's efficacy, safety, pharmacokinetics, and microbiological spectrum. Moreover, the paper discusses its potential role in contemporary clinical practice, especially considering recent supply interruptions and increasing resistance patterns. KEY MESSAGES:Ceftibuten represents an oral treatment option for respiratory and urinary tract infections, particularly where resistance to other agents limits therapeutic choices. Its favourable pharmacokinetic profile, safety both in paediatric and adult populations, and efficacy against key resistant pathogens support use within approved indications. Finally, this antibiotic offers a favourable safety profile for both patients allergic to penicillin and cephalosporins, particularly third- and fourth-generation cephalosporins. Ensuring continued access to this antibiotic may contribute to appropriate management of infections in both community and hospital settings.
