Search Results (2,875)

Background/Objectives: Nicotine-free electronic cigarettes (NFECs) are becoming increasingly popular, especially among youth and non-smokers, yet their effects on the gastrointestinal tract (GIT) remain poorly understood. This systematic review synthesizes available in vitro, in vivo, and limited human evidence on NFEC-associated changes in gastrointestinal health and function. Methods: Literature searches were conducted in Medline, Web of Science, Cochrane, and Scopus in July 2025, following PRISMA guidelines. Eligible studies examined NFEC effects on any GIT segment, including the oral cavity, liver, intestines, and microbiome. Data on study design, exposure characteristics, and main outcomes were extracted and narratively synthesized. Results: Of 111 identified records, 94 full-text articles were retrieved, and 21 studies met the inclusion criteria. Most were preclinical, with only one human pilot study. Evidence from oral cell and microbial models suggests that NFEC aerosols can induce pro-inflammatory cytokine production, impair cell viability, and disrupt microbial metabolism through their base constituents (propylene glycol, vegetable glycerine, and flavourings). Animal studies indicate possible hepatic oxidative stress, altered lipid metabolism, and gut barrier dysfunction, with some data suggesting more pronounced steatosis in nicotine-free exposures compared to nicotine-containing counterparts. Microbiome studies report reduced tight junction expression and altered neutrophil function. Conclusions: Current evidence is limited and predominantly preclinical but indicates that NFEC exposure can affect multiple aspects of gastrointestinal health. Robust longitudinal and interventional human studies are urgently needed to determine the clinical relevance of these findings and to inform regulation and public health policy. Full article

Adenosine signaling plays protective roles in gingival mitochondrial health and inflammation control, with the ectoenzyme CD73 implicated in periodontitis. Here, we investigated the effects of selective adenosine A2a receptor (A2aR) stimulation using the agonist CGS21680 in a mouse model of ligature-induced periodontitis (LIP) and in gingival fibroblast mitochondrial function. Mature C57Bl/6 mice underwent LIP and received daily intraperitoneal injections of CGS21680 (0.1 mg/Kg) or saline. After 8 days, gingival tissues and maxillae were analyzed for alveolar bone loss and Il-1β levels. In parallel, murine gingival fibroblasts (mGFs) were treated with Tnf-α (5 ng/mL) ± CGS21680 (10 µM) to assess mitochondrial function, morphology, and quality control. A2aR activation significantly reduced alveolar bone loss and Il-1β expression in vivo. In vitro, CGS21680 suppressed Tnf-α-induced Cxcl10 and Cxcl12 expressions and enhanced Vegf production. Mitochondrial analysis revealed increased mitochondrial complex levels, membrane potential, and mass, alongside reduced reactive oxygen species (ROS), proton leak, and mitochondrial stress. Ultrastructural studies showed elongated, healthier mitochondria and increased pro-fusion markers, indicating enhanced mitochondrial quality control. Overall, A2aR stimulation attenuates periodontal inflammation and confers mitoprotective effects on gingival fibroblasts, supporting its potential as a therapeutic strategy to both mitigate periodontitis progression and preserve tissue bioenergetics supporting cellular resilience. Full article

Hederagenin, a pentacyclic triterpenoid saponin from various medicinal plants, shows immense therapeutic potential; however, its inherent low bioavailability severely hinders its clinical translation. This comprehensive review synthesizes recent studies on the health benefits of hederagenin and its glycosides, critically the chemical modification strategies and pharmacological mechanisms aimed at optimizing its bioactivity. Key findings reveal that its broad anticancer and anti-inflammatory activities largely stem from its capacity to modulate crucial cellular signaling pathways, including the NF-κB, PI3K/Akt, and MAPK. Structural modification, particularly intelligent derivatization at the C-28 position, is a central strategy to overcome its pharmacokinetic deficiencies and significantly boost cytotoxicity. Furthermore, its unique pro-oxidant function within cancer cells, achieved by inhibiting the Nrf2-ARE antioxidant pathway, offers a novel approach for selective chemotherapeutics. For the clinical translation of hederagenin, we propose a strategic focus on derivatization through multi-target hybrids and sophisticated delivery systems. This approach is essential for addressing its pharmacokinetic barriers while strategically leveraging its context-dependent pro-oxidant effects. Full article

Lower respiratory infections predominantly affect children under five and the elderly, with influenza viruses and respiratory syncytial viruses (including SARS-CoV-2) being the most common pathogens. The COVID-19 pandemic has posed significant global public health challenges. While vaccination remains crucial, its efficacy is limited, highlighting the need for complementary approaches to mitigate immune hyperactivation in severe COVID-19 cases. Medicinal plants like Cannabis sativa show therapeutic potential, with over 85% of SARS-CoV-2-infected patients in China receiving traditional herbal treatments. This review explores the antiviral applications of cannabis and its bioactive compounds, particularly against SARS-CoV-2, while evaluating their pharmacological and food industry potential. Cannabis contains over 100 cannabinoids, terpenes, flavonoids, and fatty acids. Cannabinoids may block viral entry, modulate immune responses (e.g., suppressing pro-inflammatory cytokines via CB2/PPARγ activation), and alleviate COVID-19-related psychological stress. There are several challenges with pharmacological and food applications of cannabinoids, including clinical validation of cannabinoids for COVID-19 treatment and optimizing cannabinoid solubility/bioavailability for functional foods. However, rising demand for health-focused products presents market opportunities. Genetic engineering to enhance cannabinoid yields and integrated pharmacological studies are needed to unlock cannabis’s full potential in drug discovery and nutraceuticals. Cannabis-derived compounds hold promise for antiviral therapies and functional ingredients, though further research is essential to ensure safety and efficacy. Full article

Mechanical forces shape immune responses in both health and disease. PIEZO1 and PIEZO2, two mechanosensitive ion channels, have emerged as critical transducers of these forces, influencing inflammation, pain, fibrosis, and neuroimmune regulation. This review aims to synthesize the current evidence on the role of PIEZO channels in mechano-inflammation, with a specific focus on their regulatory function in neuroimmune crosstalk. A comprehensive narrative synthesis was performed using the literature from PubMed, Scopus, and Web of Science up to June 2025. Experimental, translational, and mechanistic studies involving PIEZO channels in inflammatory, fibrotic, and neuroimmune processes were included. PIEZO1 is broadly expressed in immune cells, fibroblasts, and endothelial cells, where it regulates calcium-dependent activation of pro-inflammatory pathways, such as NF-kB and STAT1. PIEZO2, enriched in sensory neurons, contributes to mechanosensory amplification of inflammatory pain. Both channels are mechanistically involved in neuroinflammation, glial activation, blood–brain barrier dysfunction, connective tissue fibrosis, and visceral hypersensitivity. PIEZO channels act as integrators of biomechanical and immunological signaling. Their roles as context-dependent gatekeepers of neuroimmune crosstalk make them attractive targets for novel therapies. Full article

Cadmium (Cd), a pervasive environmental and industrial toxicant, bioaccumulates and exerts severe detrimental effects on skeletal integrity across diverse animal species. Cd-induced bone injury manifests as osteoporosis, osteomalacia, and increased fracture risk, posing significant health and welfare concerns for wildlife and livestock inhabiting contaminated ecosystems. The pathogenesis hinges critically on the disruption of bone remodeling, a tightly regulated process orchestrated by osteoclasts (OCs) responsible for bone resorption and osteoblasts (OBs) responsible for bone formation. This comprehensive review synthesizes the latest mechanistic insights into how Cd disturbs OC and OB function and their intricate crosstalk, leading to net bone loss. Cd directly impairs OB proliferation, differentiation, and mineralization capacity through multiple pathways, including the inhibition of Wnt/β-catenin signaling, induction of oxidative stress and mitochondrial dysfunction, promotion of apoptosis and senescence, and disruption of extracellular matrix protein synthesis. Simultaneously, Cd potently stimulates excessive OC formation and activity. It achieves this by upregulating the RANKL/OPG axis, enhancing reactive oxygen species (ROS) production which activates key OC transcription factors, modulating key signaling pathways, and promoting pro-osteoclastogenic inflammatory cytokine release from bone marrow and immune cells. Critically, Cd disrupts the vital communication between OBs and OCs, perturbing the coupling signals essential for balanced remodeling. Emerging evidence highlights roles for Cd-induced epigenetic modifications and autophagy/mitophagy flux alterations. This narrative review integrates the findings from in vivo animal models and in vitro cellular studies, providing potential therapeutic interventions and mitigation strategies for Cd-induced bone toxicity. Understanding these complex and interacting mechanisms provides a foundation for identifying potential therapeutic targets to mitigate Cd bone toxicity in animals and informs ecological risk assessment and management strategies in contaminated environments. Full article

Background: Ultra-Processed Foods (UPFs) make up a growing share of older adults’ diets and may contribute to frailty through pro-inflammatory pathways. The objective of this study was to examine the association of UPF intake with frailty development and with annual changes in select frailty components. Methods: This prospective cohort study used data from 2547 participants in the Framingham Offspring Cohort. UPF intake was assessed using a food frequency questionnaire and classified according to the NOVA framework, and frailty was defined by the Fried frailty phenotype. We used cumulative and mixed logistic regression models to examine the association between daily servings of UPF and odds of developing frailty, adjusting for baseline age, education, energy intake, multivitamin use, smoking, self-rated health, history of diabetes, cancer, cardiovascular disease, and diet quality. For the frailty component analysis, we used cumulative linear regression models to assess the association between UPF intake and annual changes in grip strength, gait speed, and weight, further adjusting for BMI and physical activity. We also evaluated potential effect modification by sex and baseline age (<60 vs. ≥60 years). Results: The study population was 55.1% female, with a mean age of 60.3 ± 8.9 years. Over an average follow-up of 10.8 years, 233 participants (9.2%) developed frailty. UPF intake was not associated with frailty development in either the cumulative or mixed regression models. UPF intake was not associated with annual weight change but was inversely associated with annual change in gait speed and with annual change in grip strength in men only. Conclusions: Our findings contribute preliminary evidence that, in middle-aged and older adults, increased UPF intake is not associated with frailty but may be related to worsening muscle strength and function. Further research with a more granular approach to UPF classification is required to translate these findings to practical recommendations and to clarify their clinical significance. Full article

The World Health Organization (WHO) declared snakebite envenoming (SBE) as a neglected tropical disease in 2017. Antivenom is the gold standard of treatment, but many healthcare barriers exist, and hence, affected populations are often unable to access it. The challenge is further perpetuated by the lack of attention from national health authorities, poor regulatory systems and policies, and mismanagement of antivenom. This study aims to map the evidence regarding snake antivenom regulations globally and identify gaps in the literature to inform future research and policy. This review was conducted using the original Arksey and O’Malley framework by three independent reviewers, and the results were reported using the Preferred Reporting Items for Systematic reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR). A search strategy was developed with assistance from a librarian, and six databases were searched: PubMed, SCOPUS, ProQuest Central, Africa Wide Web, Academic Search Output, and Web of Science. Screening was conducted independently by the reviewers, using Rayyan, and conflicts were resolved with discussions. A total of 84 articles were included for data extraction. The major themes that emerged from the included studies were regarding antivenom availability, accessibility, manufacturing, and regulations. The study revealed massive gaps in terms of policies governing antivenom management, especially in Asia and Africa. The literature does not offer sufficient evidence on management guidelines for antivenom in the endemic regions, despite identifying the challenges in supply. However, significant information from Latin America revealed self-sufficient production, involvement of national health bodies in establishing efficient regulations, effective distribution nationally and regionally, and technology sharing to reduce SBE-related mortality. Full article

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and remains a significant global health challenge. Transarterial chemoembolization (TACE) is the treatment of choice for intermediate-stage HCC patients. While TACE induces localized cytotoxic and ischemic tumor necrosis, the resultant hypoxia paradoxically activates pro-angiogenic signaling pathways, which may promote tumor revascularization and recurrence. This study aimed to evaluate the plasma levels of angiogenetic factors pre- and post-TACE to assess their dynamic changes and potential clinical implications. Methods: Twenty-five intermediate-stage HCC patients were included in this monocentric prospective study. Peripheral blood samples were collected at baseline (pre-TACE), 24 h, 3 days, and 1 month post-TACE. Angiogenic factor levels were analyzed using a multiplex bead-based assay. Results: Angiopoietin-2 levels were significantly elevated three days post-TACE, followed by a gradual decline after one month. A similar pattern was observed for hepatocyte growth factor, with a marked increase at 24 h post-TACE and subsequent normalization. Endothelin-1 also exhibited a temporary increase, although it was only detected in four patients. Fibroblast growth factors (1 and 2) and vascular endothelial growth factor A were detected in a limited number of patients, which may indicate low systemic release or the need for a more sensitive detection method. Conclusions: These findings suggest that TACE induces a transient increase in angiogenic factors, likely due to tumor ischemia, tissue injury, or microenvironmental responses. Future studies should explore more sensitive detection methods and evaluate whether these factors could serve as prognostic biomarkers or therapeutic targets in HCC treatment. Full article

Using individualized approaches leads to longer-term pro-health behavior change. Both technological delivery methods and values-centered Acceptance and Commitment Therapy (ACT) are useful frameworks for personalized interventions. This investigation sought to explore the effects that valuing had on health using an internet-delivered audio and writing group-level intervention. Specifically, we replicated the use of domain-specific outcomes and idiographic motivational statements sent via text message while additionally employing individualized intervention delivery components, objectives, and statistical methods. While this intervention did not generate significant improvement in health behaviors relative to a control in a sample of 107 college student participants, it has implications for future digital health intervention design and implementation as well as the further development of theoretically consistent valuing research methods. Full article

Polytrauma is a critical global health concern characterized by immune dysregulation and a high risk of multiple organ dysfunction syndrome (MODS). Early molecular mechanisms linking trauma severity to organ injury are poorly understood. We used two rat blast-polytrauma models: a tourniquet-induced ischemia/reperfusion injury (tIRI) model and a non-ischemia/reperfusion injury (non-IRI) model. Naïve animals served as controls. RT-qPCR of 120 inflammatory genes in the lung, kidney, and liver, combined with STRING protein–protein interaction analysis, revealed distinct yet overlapping inflammatory gene signatures across all the organs. A core set of genes (Il6, Lbp, Nos2, and Lcn2) was consistently upregulated, indicating shared inflammatory pathways. Transcriptomic responses were most pronounced in the tIRI group, with greater magnitude and altered temporal dynamics, uniquely amplifying pro-inflammatory cytokines, immune cell activators, chemokines, and tissue damage markers. Lipocalin-2 (Lcn2/NGAL) emerged as a shared hub gene across all the organs within 24 h post-injury. Its expression significantly correlated with MODS activity and adverse outcomes, independent of the injury model. At 168 h, Lcn2 expression correlated with increased liver damage and NGAL levels correlated with tissue trauma severity. These findings elucidate distinct pro-inflammatory mediators and networks underlying secondary organ dysfunction, highlighting NGAL as a potential universal biomarker of trauma-induced inflammation and MODS activity, suggesting it as a therapeutic target. Full article

Zinc is an essential trace mineral for livestock, but excessive use can contribute to ecotoxicity and antimicrobial resistance. The objective of this study was to assess the impact of different zinc oxide (ZnO) levels in diets for weaned pigs on growth performance, mortality, dietary zinc flow, and environmental impacts. A 6-week feeding trial with 432 weaned pigs assessed three dietary treatments: high ZnO (pharmaceutical levels), intermediate ZnO, and low ZnO (EU recommendation). Growth performance for the growing–finishing period was modeled using the NRC (2012), and dietary Zn intake and fecal Zn excretion were estimated. Environmental impacts were analyzed via life cycle assessment (LCA) using SimaPro LCA software. High ZnO improved growth performance and reduced mortality (p < 0.05), but increased nursery fecal zinc excretion, resulting in a total fecal Zn excretion per pig of 54,125 mg, 59,485 mg, and 106,043 mg for low-, intermediate-, and high-ZnO treatments, respectively. In the nursery phase, high-ZnO treatment had the greatest impact on environmental footprint, increasing freshwater ecotoxicity and marine ecotoxicity indicators by 59.6% and 57.9%, respectively. However, high-ZnO-fed pigs had a greater body weight at the end of the nursery phase and were predicted to achieve a higher growth rate per 130 kg market pig, with fewer days to market and by sparing feed. Therefore, high-ZnO-fed pigs had reduced environmental burdens, including global warming potential, ozone depletion, land use, and mineral resource depletion. These findings demonstrate how livestock nutritionists can apply integrated modeling approaches to link animal performance with environmental outcomes within a One Health framework. Full article

The present study aimed to systematically review the anxiolytic and analgesic effects of gabapentin and pregabalin in domestic cats to assess the quality of using these medications for stress, fear, and anxiety management, and the treatment of both acute and chronic pain. The search was carried out between March and May 2025 using four databases: PubMed, Scopus, ScienceDirect, and Google Scholar. The keywords used were the combination of “pregabalin,” “gabapentin,” “analgesia,” “anxiety,” “stress”, and “cats”. Narrative reviews, as well as experimental and observational studies, were included. Experimental studies were classified as randomized controlled trials, controlled clinical trials, and prospective clinical trials, using the GRADE Pro GDP software (FP7-HEALTH.2010.3.1-1-two stage) to assess the certainty and confidence of the evidence. The initial search identified 57 manuscripts, of which 40 met the inclusion criteria. These studies focused on the management of stress, fear, and anxiety, as well as the control of acute and chronic pain in cats. Of these, 21 mention the use of gabapentin as an anxiolytic, while five report similar therapeutic effects of pregabalin. Regarding pain treatment, 12 papers and 2 papers support the use of gabapentin and pregabalin, respectively. This study confirms the validity of both drugs as therapeutic options for the management of stress, fear, and anxiety that impact the emotional welfare of cats. Furthermore, these drugs have been included in therapeutic guidelines for the control and treatment of acute and chronic pain in domestic cats. In conclusion, this systematic review supports the use of both drugs. Still, it highlights the need for more in-depth research and additional clinical trials to complement the existing evidence on the use of gabapentin and pregabalin. Full article

Lipid peroxidation driven by polyunsaturated fatty acid (PUFA) oxidation compromises feed quality and animal health. Single antioxidants (e.g., ethoxyquin (EQ), butylated hydroxytoluene (BHT)) face limitations including dose-dependent toxicity, bioaccumulation risks, and inadequate protection against multistage oxidation. Composite systems leveraging complementary mechanisms offer a promising alternative. This study evaluated synergistic efficacy of rationally formulated composite antioxidants (combining synthetic radical scavengers and metal chelators) versus single-component systems in enhancing lipid oxidative stability in high-fat animal feed. The basal diet containing oxidized oil served as the control group (CON). Seven groups were supplemented with the basal diet as follows: Treatment A, 36 g/ton Butylated Hydroxytoluene (BHT); Treatment B, 60 g/ton Ethoxyquin (EQ); Treatment C, 132 g/ton EQ; Treatment D, 10 g/ton EQ + 12 g/ton BHT; Treatment E, 10 g/ton EQ + 12 g/ton BHT + 6 g/ton Citric acid (CA); Treatment F, 20 g/ton EQ + 6 g/ton BHT + 6 g/ton CA; and treatment G, 2 g/ton EQ + 25 g/ton BHT + 6 g/ton CA. Oxidative stability was assessed over a 10-week period under natural storage (T0-T10) and acute thermal stress (120 °C drying for 2 h followed by ambient storage; HT0 to HT10). Oxidative stability was assessed via: antioxidant capacity (DPPH (2,2-Diphenyl-1-picrylhydrazyl)/ABTS (2,2′-Azinobis (3-ethylbenzothiazoline-6-sulfonic acid) scavenging, total antioxidant capacity), physical indices: Color (L*, a*, b*), and chemical oxidation markers: conjugated dienes (CD), peroxide value (PV), p-anisidine value (p-AV), malondialdehyde (MDA), acid value (AV), total oxidation (TOTOX). Superior synergistic performance of the ternary blend (Treatment E) was demonstrated versus singles (A/B/C). Retention of radical scavenging capacity was significantly enhanced, with greater stability observed under accelerated storage. Primary oxidation (PV) and secondary oxidation (MDA, p-AV) were most effectively suppressed by Treatment E. Superior color stability (minimal L* change) was maintained under thermal stress. The lowest TOTOX values were achieved across all conditions by Treatment E. Stage-specific vulnerabilities were shown by single antioxidants (BHT volatilization; pro-oxidative effects of EQ at high doses). Comprehensive, temperature-resilient protection was delivered collectively by the synergistic EQ+BHT+CA system (Treatment E) via combined radical quenching and metal chelation. The inherent limitations of individual antioxidants were effectively overcome by the optimized composite, enabling reduced total dosage while substantially extending the lipid oxidative stability period. Full article

Background/Objectives: Interstitial lung disease (ILD) is a frequent complication of rheumatoid arthritis (RA), representing the most common extra-articular manifestation (with a prevalence of about 10–60%) and the second cause of mortality. Spondyloarthritides (SpAs) are chronic arthritides that share with RA both a similar disease burden and similar therapeutical approaches. The evaluation of ILD is challenging, given the low sensitivity of X-ray and pulmonary function tests, and the radiation exposure linked to repetitive HRCT. Lung ultrasound (LUS) has shown potential in the evaluation of ILD in autoimmune diseases. The purpose of this study is to assess the prevalence of ILD in a cohort of SpA patients (pts) using LUS in comparison with healthy subjects (HSs). The secondary aim is to evaluate potential correlations between ILD and clinical features within the SpA cohort using LUS. Methods: Consecutive SpA out-patients were examined by LUS, applying the definition for pleural line irregularity (PLI) recently provided by the OMERACT taskforce for LUS in systemic sclerosis. Seventy-one intercostal spaces were studied (14 in the anterior chest, 27 lateral and 30 posterior) in all the pts/HS using an Esaote MyLab25 Gold US machine with a linear 7.5–10 MHz probe. A total pleural score was calculated. Each patient answered to Italian-validated PROs on respiratory function (Leicester and Saint-George), global health (SF-36) and dyspnea (mMRC scale). Clinical data on disease duration, disease onset, disease activity (at the moment of the examination) and methotrexate (MTX) or biologics treatment were collected from the medical records. Results: Seventy-three SpA pts (46 psoriatic arthritis -PsA- and 27 ankylosing spondylitis -AS-) and 56 HS were studied. No significant differences were demonstrated between groups (SpA vs. HS and PsA vs. AS) for age, sex, BMI and smoking habits. The total PLI score was significantly higher in SpA pts than in HS (p < 0.001). A positive correlation was found between the total PLI score and the PLI score from anterior, posterior and lateral chest. The posterior region of the chest showed a higher PLI score than the anterior and lateral regions. No statistically significant differences were found between PsA and AS. MTX use was not a risk factor for PLI (no differences were found between SpA MTX+ and SpA MTX- patients). PROs (Leicester, Saint-George and SF-36) were not related to the PLI total score. A significant correlation was found only between the SF36 score and the presence of PLI in the anterior chest. PROs were instead correlated with each other, showing a good concordance for absence/presence of symptoms. Disease activity, disease duration and age at disease-onset were not related to PLI total score. Smoking habit was found to be predictive of a significantly higher PLI score both in SpA patients and HSs. Conclusions: LUS examination shows a higher amount of PLI in SpA patients with respect to HSs. Smoking habit was the only clinical feature correlated to PLI on LUS examination in our population. Full article