Search Results (42,736)

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

C-C motif chemokine receptor-like 2 (CCRL2) is an atypical chemokine receptor (ACKR) that binds chemerin with high affinity but lacks classical G protein-coupled signaling. Instead, it functions as a non-signaling presenter of chemerin to CMKLR1-expressing cells, modulating antitumor immunity. CCRL2 is highly expressed in the tumor microenvironment and various human cancers, and its expression has been linked to delayed tumor growth in mouse models, primarily through the chemerin/CMKLR1 axis. While CCRL2’s role in immune surveillance is well established, its tumor cell-intrinsic functions remain less clear. Here, we investigated the impact of CCRL2 overexpression and knockout on tumor cell behavior in vitro. Although CCRL2 did not affect proliferation, migration, or clonogenicity in B16F0 melanoma and LLC cells, it significantly influenced spheroid morphology in B16F0 cells. Transcriptomic analysis revealed that CCRL2 modulates innate immune signaling pathways, including TLR4 and IFN-γ/STAT1, with context-dependent downstream effects. These findings suggest that CCRL2 shapes tumor architecture by rewiring inflammatory signaling networks in a cell-intrinsic manner. Further studies in other cancer types and cell models are needed to determine whether CCRL2’s regulatory role is broadly conserved and to explore its potential as a therapeutic target in solid tumors. Full article

Silica-based materials are recognized as effective functional materials across diverse industrial fields, including biomedicine (e.g., drug delivery systems (DDS), biosensors, and tissue engineering), owing to their excellent stability and physicochemical characteristics. Among them, diatom biosilica (DB), which constitutes a major part of aquatic biomass, recently gained significant attention as a valuable biomaterial following breakthroughs in its innovative surface structure, superior biocompatibility and multifunctionality. Therefore, DB is emerging as an alternative to synthetic materials used in the biomedical field. This review comprehensively examines the diverse biological properties of DB, followed by an analysis of harvesting and purification strategies. Then, the current application status of DB in two principal biomedical domains, DDS and biosensors, is evaluated. Furthermore, the convergence of these domains into theragnostic applications addresses a significant unmet clinical need for simultaneous therapeutic intervention and diagnostic monitoring, positioning DB as a transformative biomaterial solution. The unique combination of natural hierarchical architecture, tunable surface properties, and excellent biocompatibility make DB promising candidates for next-generation integrated biomedical platforms to address the growing demand of personalized medicine and precision healthcare solutions. Full article

Wound healing is a physiological process including haemostasis, inflammation, proliferation, and remodelling. Acute wounds typically follow a predictable healing process, whereas chronic wounds cause prolonged inflammation and infection, failing to progress through typical healing phases and presenting significant clinical challenges. A combination of wound care techniques and therapeutic agents is required to manage chronic wounds effectively. Curcumin is a bioactive compound derived from Curcuma longa and has gained attention for its potent antioxidant, anti-inflammatory, and antibacterial properties. The first part of this review aims to provide a comprehensive overview of the physiology of wound healing, focusing on the pathophysiology and management of acute and chronic wounds, followed by the biological activity of curcumin in wound healing, emphasising its impact on promoting tissue repair. Finally, this review explores curcumin-loaded dressings, such as hydrogels, nanofibrous membranes, polymeric micelles, and films, offering controlled drug release and targeted curcumin delivery to enhance wound healing. Full article

Diabetes mellitus (DM) is a complex metabolic disease characterized by significantly elevated blood glucose levels as a result of dysfunctional or impaired pancreatic β-cells, leading to insulin deficiency. This condition can result in severe complications, including cardiovascular diseases, kidney failure, vision impairment, and nerve damage. Currently available anti-diabetic drugs do not fully prevent the progression of these complications. Moreover, they often have significant side effects. The gut microbiota plays a crucial role in influencing diet, energy metabolism, and blood glucose levels. Research shows a strong link between microbiota dysbiosis and DM, as well as the severity of its complications. Commensal bacteria can help manage blood glucose levels, reduce inflammation, regulate metabolism, and enhance the gut barrier. Conversely, opportunistic pathogens can worsen insulin resistance, promote metabolic disorders, disrupt gut integrity, and affect appetite and weight. This article describes the characteristics of gut microbiota in various types of DM and explores the role of the “gut microbiota–metabolite–signaling pathway” axis in DM and its complications. In addition, it highlights the therapeutic potential of traditional Chinese medicine and dietary interventions through modulation of the gut microbiota and metabolites. The aim is to provide comprehensive evidence supporting the integration of TCM dietary therapy, targeted dietary strategies, and specific probiotics as alternative and complementary therapies for DM and its complications. Full article

Background/Objectives: Fluorothiazinone (FT), a small molecule of the 2,4-disubstituted-4H-[1,3,4]-thiadiazine-5-one class, is known to inhibit the type III secretion system (T3SS) in Gram-negative bacteria and has shown therapeutic potential in animal models and clinical trials. Given the evolutionary relationship between the T3SS and the bacterial flagellar apparatus, this study aimed to investigate the effects of FT on bacterial motility and flagellum assembly. Methods: Motility was assessed in Pseudomonas aeruginosa, Proteus mirabilis, pathogenic Escherichia coli, and Listeria monocytogenes using a semisolid agar assay and a microfluidic motility system. The mechanism of FT’s action was further examined through time-course analysis, Western blotting of surface flagella proteins, and transmission electron microscopy (TEM). Results: FT inhibited motility of P. aeruginosa, P. mirabilis, and E. coli in a dose-dependent manner, while L. monocytogenes motility remained unaffected. The inhibitory effect was not immediate but delayed 2–3 h post FT addition. Western blotting revealed the absence of surface flagella in EHEC grown with FT, and TEM confirmed structural disruption of flagella in P. mirabilis. Conclusions: FT selectively inhibits flagellum-based motility in Gram-negative bacteria. Obtained data suggested FT interference with flagellum biosynthesis rather than disruption of rotation. Motility inhibition can contribute to FT therapeutic effects on Gram-negative bacterial infections. Full article

Retinitis pigmentosa is a group of inherited retinal dystrophies characterized by progressive photoreceptor cell loss leading to irreversible vision loss. Affecting approximately 1 in 4000 individuals worldwide, retinitis pigmentosa exhibits significant genetic heterogeneity, with mutations in genes such as RHO, PRPF31, RPE65, USH2A, and NR2E3, which contribute to its diverse clinical presentation. This review outlines the genetic basis of retinitis pigmentosa and explores cutting-edge gene-based therapeutic strategies. Luxturna (voretigene neparvovec-rzyl), the first FDA-approved gene therapy targeting RPE65 mutations, represents a milestone in precision ophthalmology, while OCU400 is a gene-independent therapy that uses a modified NR2E3 construct to modulate retinal homeostasis across different RP genotypes. Additionally, CRISPR–Cas genome-editing technologies offer future potential for the personalized correction of specific mutations, though concerns about off-target effects and delivery challenges remain. The article also highlights MCO-010, a novel optogenetic therapy that bypasses defective phototransduction pathways, showing promise for patients regardless of their genetic profile. Moreover, QR-1123, a mutation-specific antisense oligonucleotide targeting the P23H variant in the RHO gene, is under clinical investigation for autosomal dominant RP and has shown encouraging preclinical results in reducing toxic protein accumulation and preserving photoreceptors. SPVN06, another promising candidate, is a mutation-agnostic gene therapy delivering RdCVF and RdCVFL via AAV to support cone viability and delay degeneration, currently being evaluated in a multicenter Phase I/II trial for patients with various rod–cone dystrophies. Collectively, these advances illustrate the transition from symptom management toward targeted, mutation-specific therapies, marking a major advancement in the treatment of RP and inherited retinal diseases. Full article

Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder specific to pregnancy, typically presenting in the third trimester. It is characterized by pruritus, elevated serum bile acids, and abnormal liver function tests. While maternal symptoms resolve postpartum, ICP poses significant risks to fetal health, including spontaneous preterm labor, meconium-stained amniotic fluid, and stillbirth. This review aims to synthesize current knowledge on the pathogenesis, diagnosis, and management and highlight emerging research and possible therapy directions in ICP. A comprehensive review of recent literature was conducted, focusing on molecular mechanisms, clinical management guidelines, fetal outcomes, and novel therapeutics under investigation. Ursodeoxycholic acid (UDCA) remains the primary pharmacologic treatment of intrahepatic cholestasis of pregnancy; however, its effect on perinatal outcomes is debated. Investigational therapies—including Volixibat, FXR agonists, 4-phenylbutyrate, and NorUDCA—are under exploration. These emerging therapies hold the potential to improve both maternal symptoms and perinatal outcomes by addressing the underlying pathophysiology of ICP more effectively than current standard treatment. Additionally, emerging biomarkers and machine-learning tools hold promise for improved diagnosis and personalized care. ICP continues to pose diagnostic and therapeutic challenges. While maternal outcomes are generally favorable, optimizing fetal safety requires timely diagnosis, stratified risk assessment, and evidence-based delivery planning. Future research should prioritize identifying predictive biomarkers, refining treatment algorithms, and assessing long-term outcomes for both mothers and offspring. Special attention should also be given to the investigation of novel therapeutic targets. Full article

Dystonia-myoclonus syndrome is a rare neurological condition characterized by involuntary muscle contractions and myoclonic jerks, significantly impairing daily functioning. Pharmacological management is often ineffective, prompting consideration of alternative therapeutic interventions such as deep brain stimulation (DBS). This report describes a novel clinical case involving a 38-year-old female with severe dystonic and myoclonic symptoms associated with a pathogenic mutation in the KCNN2 gene (DYT34). Bilateral DBS targeting the internal segment of the globus pallidus (GPi) resulted in marked and sustained symptom improvement, notably reducing dystonic posturing and myoclonic movements over the 24-month follow-up period. Neuropsychological and neurologopedic assessments revealed no adverse effects on cognition or speech. This represents the first sufficient effect of GPi-DBS in a patient with a genetically confirmed KCNN2 mutation, highlighting its potential efficacy and underscoring the need for genetic testing in patients presenting with dystonia-myoclonus syndromes. Full article

Isoeugenol is a phenylpropanoid that is commonly found in essential oils and has been commonly used as a flavoring agent in the culinary field and an anesthetic in fish. Yet despite its similarity to well-known eugenol, there is a lack of data regarding how isoeugenol would directly modulate neuronal excitability to interfere with pain signaling. Here, we studied the effects of isoeugenol on voltage-activated Na⁺ currents (I_Na) as a means of starting to close the gap regarding the inhibitory properties of isoeugenol on neuronal excitability. We used rat dorsal root ganglia neurons under whole cell voltage clamp for the isolation of I_Na.. We show that isoeugenol effectively inhibits I_Na fully, reversibly, and in a dose-dependent manner. Our detailed analysis also indicates the direct interaction of isoeugenol with voltage-gated Na⁺ channels (VGSC) is likely state-dependent, as the inhibitory activity is enhanced by membrane depolarization. This effect is beneficial for pain management, as the drug would act more effectively as neuronal activity is promoted by membrane depolarization. Our data indicates a direct inhibition of VGSC by isoeugenol might constitute the main mechanism whereby this phenylpropanoid produces analgesia. This study serves as a basis for future approaches to deeply investigate the therapeutic potential of this drug or its derivatives. Full article

Pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive malignancies, with dismal survival rates. Cannabinoids have shown anticancer properties in various cancers, including PDAC. This study aimed to evaluate the anticancer effects of cannabinoids, individually and in combination, and to elucidate their mechanisms of action in a murine PDAC model (KPC mice, KRASWT/G12D/TP53WT/R172H/Pdx1-Cre+/+) that mimics human disease. Additionally, the study explored the potential link between cannabinoid action, gut microbiota modulation, and bile acid (BA) metabolism. PDAC cell lines and KPC mice were treated with delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), either as monotherapy or in combination. Faecal pellets, caecal contents, plasma, and tissues were collected at the survival endpoint for analysis. BA profiling was performed using mass spectrometry, and the faecal microbiota was characterised by sequencing the V3-V4 region of the 16S rRNA gene. While CBD and THC synergistically reduced cell viability in PDAC cell lines, only CBD monotherapy improved survival in KPC mice. Extended survival with CBD was accompanied by changes in gut microbiota composition and BA metabolism, suggesting a possible association. Notably, the effects of CBD were different from those observed with THC alone or in combination with CBD. The study highlights a distinct role for CBD in altering BA profiles, suggesting these changes may predict responses to cannabidiol in PDAC models. Furthermore, the findings propose that targeting BA metabolism could offer a novel therapeutic strategy for PDAC. Full article

There is an urgent need for new approaches and strategies for the introduction of antioxidant drugs in medicine. Despite hundreds of clinical trials with potential antioxidants, no antioxidant drugs have so far been developed for clinical use; this is mainly as a result of commercial reasons, but also due to insufficient data for regulatory authority approval. Antioxidant activity is a physiological process essential for healthy living. However, increased production of toxic free radicals and reactive oxygen species is observed in many clinical conditions, which are associated with serious and sometimes irreversible damage. Antioxidant drug strategies may involve short- to long-term therapeutic applications for the purpose of prevention, treatment, or post-treatment effects of a disease. These strategies are different for each disease and may include the design of protocols for the inhibition of oxidative damage through iron chelation, enhancing antioxidant defences by increasing the production of endogenous antioxidants, and activating antioxidant mechanisms, as well as the administration of synthetic and natural antioxidants. Both the improvement of antioxidant biomarkers and clinical improvement or disease remission are required to suggest effective therapeutic intervention. More concerted efforts, including new academic strategies, are required for the development of antioxidant drugs in clinical practice. Such efforts should be similar to the fulfilment of orphan or emergency drug regulatory requirements, which, in most cases, involve the treatment or clinical improvement of rare or severe diseases such as neurodegenerative diseases and cancer. Promising results of antioxidant therapeutic interventions include mainly the repurposing of the iron chelating/antioxidants drugs deferiprone (L1) and deferoxamine, and also the iron-binding drug N-acetylcysteine (NAC). In some clinical trials, the lack of pharmacodynamic and ferrikinetic data, wrong posology, and insufficient monitoring have resulted in inconclusive findings. Future strategies involving appropriate protocols and drug combinations, such as L1 and NAC, appear to improve the prospect of developing antioxidant drug therapies in different diseases, including those associated with ferroptosis. New strategies may also involve the use of pro-drugs such as aspirin, which is partly biotransformed into iron chelating/antioxidant metabolites with chemopreventive properties in cancer, and also in other therapeutic interventions. A consortium of expert academics on regulatory drug affairs and clinical trials could increase the prospects for antioxidant drug development in medicine. Full article

Background: Interoception, the multifaceted perception of internal bodily signals, is crucial for homeostasis, emotional regulation, and overall well-being. Physical exercise significantly influences interoceptive mechanisms through its varied physiological, neurobiological, and psychological impacts. Despite its potential to enhance this internal sensing across its dimensions and foster adaptive behaviors like self-regulation, exercise remains an underutilized therapeutic approach. Objective: This narrative review explores the current understanding of the interplay between exercise and interoception, examining its resulting impact on both mental and physical health. Method: A comprehensive literature search was conducted on PubMed using keywords such as “interoception,” “exercise,” and “well-being.” Article selection prioritized empirical studies, reviews, and influential theoretical papers. The synthesis of the literature was performed through a thematic analysis, structured around three primary mechanisms: physiological changes, neurobiological adaptations, and psychological benefits. Key Findings: Engaging in exercise improves interoceptive function by inducing physiological changes, fostering neurobiological adaptations, and yielding psychological advantages such as reduced stress. This enhancement in internal bodily sensing, encompassing its various dimensions, and promotion of adaptive behaviors has notable consequences for well-being. Conclusions and Future Directions: Exercise presents a valuable and readily available means to enhance interoceptive processing and encourage adaptive behaviors, with substantial positive implications for well-being throughout life. Future studies should focus on identifying the most effective exercise approaches tailored to individual requirements and exploring their specific impact on different interoceptive dimensions. Integrating exercise into clinical treatment plans and public health strategies offers a promising path to substantially boost well-being. Full article

Obesity, a major global health concern, is associated with systemic metabolic dysregulation. Spexin, a peptide implicated in appetite control and energy balance, may represent a biomarker and therapeutic target in obesity management. This study aimed to investigate tissue-specific modulation of spexin expression in obese male rats subjected to aerobic exercise and/or metformin treatment. Thirty-six Sprague–Dawley rats were randomly assigned to six groups (n = 6 per group): (i) control, (ii) obese control, (iii) exercise, (iv) metformin, (v) metformin + exercise, and (vi) a decapitation baseline group. Obesity was induced via a 12-week high-calorie diet. Subsequently, interventions were applied over 4 weeks: treadmill running (30 min/day, 5 days/week) and/or metformin (150 mg/kg/day). Post-intervention, body weight significantly decreased in intervention groups (p < 0.001) exercise (−13.7%), metformin (−14.6%), and metformin + exercise (−21.1%) compared to the obese control group. ELISA revealed tissue-specific effects on spexin expression. In skeletal muscle, spexin levels were highest in controls (628 ± 160.5 pg/mL), with a significant reduction in the metformin + exercise group (349 ± 84.7 pg/mL; p = 0.003, Cohen’s d = 2.17). In the liver, the control group showed the highest expression (443 ± 240.8 pg/mL), while metformin + exercise yielded the lowest (254 ± 20.4 pg/mL). In contrast, heart tissue maintained elevated spexin levels across all intervention groups, with the metformin + exercise group nearly matching control levels (617 ± 25.2 vs. 618 ± 53.2 pg/mL). Immunohistochemistry confirmed these patterns, with the highest cardiac histoscore in the metformin + exercise group (2.34 ± 0.09). Hierarchical clustering underscored distinct tissue-specific expression patterns, separating muscle from liver and heart. Collectively, these findings suggest that spexin is differentially regulated by exercise and metformin, with joint effects and complex, tissue-specific modulation. This highlights spexin’s potential as a biomarker and therapeutic target in precision obesity interventions. Full article

Background/objectives: Melanoma is one of the deadliest forms of malignant cancers; ultraviolet radiation exposure together with genetic mutations, such as BRAF, represent the main risk factors and are involved in metastatic dissemination. Previous studies demonstrated the anti-emetic and anti-proliferative effects of the flavonoid genistein and the turmeric curcumin in cancers. This study aimed at investigating the anticancer effects of curcumin, genistein and their association in melanoma cells. Methods: Human A375 and CHL-1 cell lines were cultured and treated with different concentrations of curcumin or genistein or curcumin + genistein for 24 h according to IC50. Results: Genistein and curcumin induced cell death, as demonstrated by MTT assay and FDA/PI staining. The anti-apoptotic protein Bcl-2 was significantly reduced after curcumin and curcumin + genistein treatment, but unexpectedly not with genistein alone. Curcumin and genistein significantly increased DNA fragmentation, thus indicating apoptosis induction. Moreover, comet assay confirmed that curcumin and genistein stimulated cell death, as quantified by measuring the displacement between the ‘comet head’ and the resulting ‘tail’. FAK protein expression was significantly reduced by genistein and curcumin in CHL-1 cells and after the treatment with genistein + curcumin in the most aggressive A375 cells. These anti-proliferative effects were confirmed by scratch assay and phospho-p38 reduction. Moreover, both curcumin and genistein alone and in association inhibited cell adhesion, thus indicating that these nutraceuticals could reduce invasion and metastasis. Conclusion: The obtained results provided new insights for the anticancer effects of genistein and curcumin, which could be used to improve therapeutic adherence and drug response. Full article