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Search Results (208)

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Keywords = non-steroidal anti-inflammatory agents

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51 pages, 2489 KiB  
Review
Immunomodulatory Effects of Gold Nanoparticles: Impacts on Immune Cells and Mechanisms of Action
by Khadijeh Koushki, Prapannajeet Biswal, Geraldine Vidhya Vijay, Mahvash Sadeghi, Sajad Dehnavi, Ngoc Tuyet Tra, Sai Kumar Samala, Mahdieh Yousefi Taba, Arjun Balaji Vasan, Emily Han, Yuri Mackeyev and Sunil Krishnan
Nanomaterials 2025, 15(15), 1201; https://doi.org/10.3390/nano15151201 - 6 Aug 2025
Abstract
Traditional anti-inflammatory medications—such as corticosteroids, biological agents, and non-steroidal anti-inflammatory drugs—are commonly employed to mitigate inflammation, despite their potential for debilitating side effects. There is a growing need for alternative next-generation therapies for symptomatic, unchecked, and/or detrimental inflammation with more favorable adverse effect [...] Read more.
Traditional anti-inflammatory medications—such as corticosteroids, biological agents, and non-steroidal anti-inflammatory drugs—are commonly employed to mitigate inflammation, despite their potential for debilitating side effects. There is a growing need for alternative next-generation therapies for symptomatic, unchecked, and/or detrimental inflammation with more favorable adverse effect profiles. The long history of use of gold salts as anti-inflammatory agents and the more recent exploration of gold nanoparticle (AuNP) formulations for clinical indications suggest that the targeted delivery of nanoparticles to inflammatory sites may be a promising approach worth investigating. Coupled with peptides that specifically target immune cells, AuNPs could potently counteract inflammation. Here, we provide an overview of the selective infiltration of AuNPs into immune cells and summarize their interactions with and impact on these cells. Additionally, we provide a comprehensive mechanistic summary of how AuNPs exert their anti-inflammatory effects. Full article
(This article belongs to the Special Issue Roadmaps for Nanomaterials in Radiation Therapy)
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46 pages, 2713 KiB  
Article
Anti-Inflammatory and Antiplatelet Interactions on PAF and ADP Pathways of NSAIDs, Analgesic and Antihypertensive Drugs for Cardioprotection—In Vitro Assessment in Human Platelets
by Makrina Katsanopoulou, Zisis Zannas, Anna Ofrydopoulou, Chatzikamari Maria, Xenophon Krokidis, Dimitra A. Lambropoulou and Alexandros Tsoupras
Medicina 2025, 61(8), 1413; https://doi.org/10.3390/medicina61081413 - 4 Aug 2025
Abstract
Cardiovascular disease (CVD) is the leading cause of death worldwide, with pathophysiological mechanisms often involving platelet activation and chronic inflammation. While antiplatelet agents targeting adenosine diphosphate (ADP)-mediated pathways are well established in CVD management, less is known about drug interactions with the platelet-activating [...] Read more.
Cardiovascular disease (CVD) is the leading cause of death worldwide, with pathophysiological mechanisms often involving platelet activation and chronic inflammation. While antiplatelet agents targeting adenosine diphosphate (ADP)-mediated pathways are well established in CVD management, less is known about drug interactions with the platelet-activating factor (PAF) pathway, a key mediator of inflammation. This study aimed to evaluate the effects of several commonly used cardiovascular and anti-inflammatory drug classes—including clopidogrel, non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin II receptor blockers (ARBs), β-blockers, and analgesics—on platelet function via both the ADP and PAF pathways. Using human platelet-rich plasma (hPRP) from healthy donors, we assessed platelet aggregation in response to these two agonists in the absence and presence of graded concentrations of each of these drugs or of their usually prescribed combinations. The study identified differential drug effects on platelet aggregation, with some agents showing pathway-specific activity. Clopidogrel and NSAIDs demonstrated expected antiplatelet effects, while some (not all) antihypertensives exhibited additional anti-inflammatory potential. These findings highlight the relevance of evaluating pharmacological activity beyond traditional targets, particularly in relation to PAF-mediated inflammation and thrombosis. This dual-pathway analysis may contribute to a broader understanding of drug mechanisms and inform the development of more comprehensive therapeutic strategies for the prevention and treatment of cardiovascular, hypertension, and inflammation-driven diseases. Full article
(This article belongs to the Section Pharmacology)
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27 pages, 1269 KiB  
Review
Old and New Analgesic Acetaminophen: Pharmacological Mechanisms Compared with Non-Steroidal Anti-Inflammatory Drugs
by Hironori Tsuchiya and Maki Mizogami
Future Pharmacol. 2025, 5(3), 40; https://doi.org/10.3390/futurepharmacol5030040 - 22 Jul 2025
Viewed by 459
Abstract
Although it is more than a century since it was first marketed, acetaminophen remains one of the most popular analgesic agents. In addition, acetaminophen has recently been applied to multimodal analgesia in combination with non-steroidal anti-inflammatory drugs, and its consumption significantly increased during [...] Read more.
Although it is more than a century since it was first marketed, acetaminophen remains one of the most popular analgesic agents. In addition, acetaminophen has recently been applied to multimodal analgesia in combination with non-steroidal anti-inflammatory drugs, and its consumption significantly increased during the pandemic of coronavirus disease 2019 as well as diclofenac and ibuprofen. However, the detailed mode of analgesic action of acetaminophen is still unclear. In the present study, we comprehensively discuss conventional, recognized, and postulated mechanisms of analgesic acetaminophen and highlight the current mechanistic concepts while comparing with diclofenac and ibuprofen. Acetaminophen inhibits cyclooxygenase with selectivity for cyclooxygenase-2, which is higher than that of ibuprofen but lower than that of diclofenac. In contrast to diclofenac and ibuprofen, however, anti-inflammatory effects of acetaminophen depend on the extracellular conditions of inflamed tissues. Since the discovery of cyclooxygenase-3 in the canine brain, acetaminophen had been hypothesized to inhibit such a cyclooxygenase-1 variant selectively. However, this hypothesis was abandoned because cyclooxygenase-3 was revealed not to be physiologically and clinically relevant to humans. Recent studies suggest that acetaminophen is deacetylated to 4-aminophenol in the liver and after crossing the blood–brain barrier, it is metabolically converted into N-(4-hydroxyphenyl)arachidonoylamide. This metabolite exhibits bioactivities by targeting transient receptor potential vanilloid 1 channel, cannabinoid receptor 1, Cav3.2 calcium channel, anandamide, and cyclooxygenase, mediating acetaminophen analgesia. These targets may be partly associated with diclofenac and ibuprofen. The perspective of acetaminophen as a prodrug will be crucial for a future strategy to develop analgesics with higher tolerability and activity. Full article
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60 pages, 3898 KiB  
Review
The Therapeutic Potential of Phytochemicals Unlocks New Avenues in the Management of Rheumatoid Arthritis
by Kalina A. Nikolova-Ganeva, Nikolina M. Mihaylova, Lidiya A. Kechidzhieva, Kristina I. Ivanova, Alexander S. Zarkov, Daniel L. Parzhanov, Momchil M. Ivanov and Andrey S. Marchev
Int. J. Mol. Sci. 2025, 26(14), 6813; https://doi.org/10.3390/ijms26146813 - 16 Jul 2025
Viewed by 503
Abstract
Rheumatoid arthritis (RA) is a progressive and systemic autoimmune disease, characterized by a chronic inflammatory process, affecting the lining of the synovial joints, many body organs/systems, and blood vessels. Its pathological hallmarks are hyperplasic synovium, bone erosion, and progressive joint destruction. Rheumatoid arthritis [...] Read more.
Rheumatoid arthritis (RA) is a progressive and systemic autoimmune disease, characterized by a chronic inflammatory process, affecting the lining of the synovial joints, many body organs/systems, and blood vessels. Its pathological hallmarks are hyperplasic synovium, bone erosion, and progressive joint destruction. Rheumatoid arthritis affects over 20 million people, with a worldwide prevalence of 0.5–1.0%, exhibiting gender, ethnic, and geographical differences. The progressive disability severely impairs physical motion and quality of life and is finally leading to a shortened life span. The pathogenesis of RA is a complex and still poorly understood process in which genetic and environmental factors are principally associated. Current treatment mostly relies on conventional/non-biological disease-modifying anti-rheumatic drugs (cDMARDs), analgesics, non-steroidal anti-inflammatory drugs, glucocorticoids, steroids, immunosuppresants, and biologic DMARDs, which only control inflammation and pain. Along with side effects (drug toxicity and intolerance), these anti-rheumatic drugs possess limited efficacy. Therefore, the discovery of novel multi-target therapeutics with an improved safety profile that function as inhibitors of RA-linked signaling systems are in high demand, and this is in the interest of both patients and clinicians. Plant-derived extracts, nutritional supplements, dietary medicine, and molecules with anti-inflammatory activity represent promising adjuvant agents or alternatives for RA therapeutics. This review not only aims to discuss the basic features of RA pathogenesis, risk factors, and signaling pathways but also highlights the research progress in pre-clinical RA in in vitro and in vivo models, revealing new avenues in the management of the disease in terms of comprehensive multidisciplinary strategies originating from medicinal plants and plant-derived molecules. Full article
(This article belongs to the Special Issue Natural Products as Multitarget Agents in Human Diseases)
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19 pages, 4731 KiB  
Article
The Evaluation of Potential Anticancer Activity of Meloxicam—In Vitro Study on Amelanotic and Melanotic Melanoma
by Marta Karkoszka-Stanowska, Zuzanna Rzepka and Dorota Wrześniok
Int. J. Mol. Sci. 2025, 26(13), 5985; https://doi.org/10.3390/ijms26135985 - 22 Jun 2025
Viewed by 538
Abstract
Meloxicam (MLX), a member of the non-steroidal anti-inflammatory drugs (NSAIDs), is a preferential inhibitor of cyclooxygenase-2 (COX-2) responsible for the synthesis of pro-inflammatory prostaglandins. MLX, due to its inhibition of the COX-2 enzyme, which is overexpressed in many cancers, including melanoma, leading to [...] Read more.
Meloxicam (MLX), a member of the non-steroidal anti-inflammatory drugs (NSAIDs), is a preferential inhibitor of cyclooxygenase-2 (COX-2) responsible for the synthesis of pro-inflammatory prostaglandins. MLX, due to its inhibition of the COX-2 enzyme, which is overexpressed in many cancers, including melanoma, leading to rapid growth, angiogenesis, and metastasis, represents a potentially important compound with anticancer activity. This study aimed to investigate the potential anticancer activity of meloxicam against amelanotic C32 and melanotic COLO 829 melanoma cell lines. The objective was achieved by assessing cell metabolic activity using the WST-1 assay and analyzing mitochondrial potential, levels of reduced thiols, annexin, and caspases 3/7, 8, and 9 by imaging cytometry, as well as assessing reactive oxygen species (ROS) levels using the H2DCFDA probe. The amelanotic melanoma C32 was more sensitive to MLX exposure, thus exhibiting antiproliferative effects, a disruption of redox homeostasis, a reduction in mitochondrial potential, and an induction of apoptosis. The results provide robust molecular evidence supporting the pharmacological effects of MLX, highlighting its potential as a valuable agent for in vivo melanoma treatment. Full article
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30 pages, 555 KiB  
Review
Comprehensive Approaches to Pain Management in Postoperative Spinal Surgery Patients: Advanced Strategies and Future Directions
by Dhruba Podder, Olivia Stala, Rahim Hirani, Adam M. Karp and Mill Etienne
Neurol. Int. 2025, 17(6), 94; https://doi.org/10.3390/neurolint17060094 - 18 Jun 2025
Viewed by 1315
Abstract
Effective postoperative pain management remains a major clinical challenge in spinal surgery, with poorly controlled pain affecting up to 50% of patients and contributing to delayed mobilization, prolonged hospitalization, and risk of chronic postsurgical pain. This review synthesizes current and emerging strategies in [...] Read more.
Effective postoperative pain management remains a major clinical challenge in spinal surgery, with poorly controlled pain affecting up to 50% of patients and contributing to delayed mobilization, prolonged hospitalization, and risk of chronic postsurgical pain. This review synthesizes current and emerging strategies in postoperative spinal pain management, tracing the evolution from opioid-centric paradigms to individualized, multimodal approaches. Multimodal analgesia (MMA) has become the cornerstone of contemporary care, combining pharmacologic agents, such as non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and gabapentinoids, with regional anesthesia techniques, including erector spinae plane blocks and liposomal bupivacaine. Adjunctive nonpharmacologic modalities like early mobilization, cognitive behavioral therapy, and mindfulness-based interventions further optimize recovery and address the biopsychosocial dimensions of pain. For patients with refractory pain, neuromodulation techniques such as spinal cord and peripheral nerve stimulation offer promising results. Advances in artificial intelligence (AI), biomarker discovery, and nanotechnology are poised to enhance personalized pain protocols through predictive modeling and targeted drug delivery. Enhanced recovery after surgery protocols, which integrate many of these strategies, have been shown to reduce opioid use, hospital length of stay, and complication rates. Nevertheless, variability in implementation and the need for individualized protocols remain key challenges. Future directions include AI-guided analytics, regenerative therapies, and expanded research on long-term functional outcomes. This review provides an evidence-based framework for pain control following spinal surgery, emphasizing integration of multimodal and innovative approaches tailored to diverse patient populations. Full article
(This article belongs to the Section Pain Research)
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21 pages, 4208 KiB  
Review
Pulmonary Involvement in Systemic Lupus Erythematosus: A Potentially Overlooked Condition
by Ilaria Mormile, Gerardo Nazzaro, Marco Filippelli, Francesca Della Casa, Mauro Mormile, Amato de Paulis and Francesca Wanda Rossi
Biomedicines 2025, 13(6), 1485; https://doi.org/10.3390/biomedicines13061485 - 16 Jun 2025
Viewed by 1104
Abstract
Systemic lupus erythematosus (SLE) is a pleiotropic disease that can present in numerous forms, ranging from mild mucocutaneous symptoms to severe manifestations affecting multiple organs. SLE has the potential to impact any segment of the respiratory system, exhibiting a range of severity levels [...] Read more.
Systemic lupus erythematosus (SLE) is a pleiotropic disease that can present in numerous forms, ranging from mild mucocutaneous symptoms to severe manifestations affecting multiple organs. SLE has the potential to impact any segment of the respiratory system, exhibiting a range of severity levels throughout the different stages of the disease. Pulmonary manifestations in SLE patients can be classified as primary (i.e., directly related to SLE and to immune-mediated damage), secondary to other SLE manifestations (e.g., nephrotic syndrome, renal failure, congestive heart failure), and comorbidities (e.g., infections, cancers, overlapping primary respiratory diseases). Understanding and correctly managing lung involvement in SLE is crucial because pulmonary complications are common and can significantly impact morbidity and mortality in affected patients. Early recognition and appropriate treatment can prevent irreversible lung damage, improve quality of life, and reduce the risk of life-threatening complications. Treatment algorithms are based on the suppression of inflammation, with or without the need for dedicated, supportive care. According to disease severity, available treatments include nonsteroidal anti-inflammatory drugs, corticosteroids, immunosuppressants, and biological agents. In this review, we aim to summarize the current knowledge on lung involvement in SLE and then focus on the management and treatment approaches available for the different forms. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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17 pages, 927 KiB  
Article
Multi-Targeting Valproic Acid Conjugates as Potent Agents Against Inflammation and Hyperlipidemia
by Panagiotis Theodosis-Nobelos and Eleni A. Rekka
Molecules 2025, 30(11), 2339; https://doi.org/10.3390/molecules30112339 - 27 May 2025
Viewed by 576
Abstract
Novel derivatives of valproic acid with biologically active moieties, such as thiomorpholine, 4-aminopyridine, serine methyl ester, trolox and the cinnamic acid derivative [(E)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)acrylic acid], were synthesized at satisfactory yields. The conjugation of these moieties was based on the rationale [...] Read more.
Novel derivatives of valproic acid with biologically active moieties, such as thiomorpholine, 4-aminopyridine, serine methyl ester, trolox and the cinnamic acid derivative [(E)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)acrylic acid], were synthesized at satisfactory yields. The conjugation of these moieties was based on the rationale of design and evaluation of compounds with selected structural characteristics, aiming at derivatives with multiple targets. These compounds reduced acute inflammation considerably and, in most cases, more than several highly used, well-known, non-steroidal anti-inflammatory drugs. They also offered the inhibition of soybean lipoxygenase, and some of them (compounds 5 and 6) possessed radical scavenging and lipid peroxidation attenuating effects. Their antioxidant capacity was several times higher than that of the established antioxidant trolox. All the tested compounds decreased plasma lipid markers in tyloxapol-induced hyperlipidemia in rats. Compound 2 resulted in 71.1%, 52.8% and 79.1% decrease in total cholesterol, triglycerides and LDL-cholesterol, respectively, at 150 μmol/kg (i.p.). The effect on total and LDL cholesterol is comparable or equal to that of simvastatin, a hypocholesterolemic 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA) inhibitor, however, with additionally great triglyceride-decreasing effect compared to simvastatin. Thus, the synthesized compounds may be a valuable addition to multi-functional agents acting against various degenerative disorders that implicate inflammation and lipid derangement. Full article
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13 pages, 230 KiB  
Article
Does Metamizole Cause Less Acute Kidney Injury than Non-Steroidal Anti-Inflammatory Drugs When Combined with Diuretics and Antihypertensives?
by Dulce Maria Calvo, Luis Carlos Saiz, Leire Leache, Maria C. Celaya, Marta Gutiérrez-Valencia, Alvaro Alonso and Juan Erviti
Toxics 2025, 13(5), 417; https://doi.org/10.3390/toxics13050417 - 21 May 2025
Viewed by 1373
Abstract
The concurrent use of (a) diuretics, (b) renin–angiotensin–aldosterone system inhibitors (RAASIs), and (c) non-steroidal anti-inflammatory drugs (NSAIDs) or metamizole, known as the triple whammy (TW) combination, increases the risk of acute kidney injury (AKI). This study compared TWs including metamizole versus NSAIDs regarding [...] Read more.
The concurrent use of (a) diuretics, (b) renin–angiotensin–aldosterone system inhibitors (RAASIs), and (c) non-steroidal anti-inflammatory drugs (NSAIDs) or metamizole, known as the triple whammy (TW) combination, increases the risk of acute kidney injury (AKI). This study compared TWs including metamizole versus NSAIDs regarding hospitalisation for AKI, need for renal replacement therapy (RRT), and all-cause mortality during hospitalisation. Serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) changes in the first year after TW initiation were also assessed. A nested case–control study was conducted within a cohort of adults receiving TW therapy (2009–2018). Logistic regression models analysed the associations between TW type and outcomes. Among 65,077 individuals (mean age 79.7 years; 26.3% male), TW including an NSAID was associated with a lower risk of AKI-related hospitalisation [adjusted odds ratio (aOR) 0.81, 95%CI 0.74–0.87] and all-cause mortality (aOR 0.64, 95%CI 0.49–0.82) compared to TW including metamizole. No significant differences were found in other variables. These findings suggest that TW including an NSAID may reduce the risk of AKI-related hospitalisation and mortality compared to TW including metamizole, although kidney function parameters remained unaffected. Further research is needed to confirm these results. Full article
(This article belongs to the Special Issue Nephrotoxicity Induced by Drugs and Chemicals in the Environment)
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11 pages, 224 KiB  
Case Report
Use of Cyclosporine and Itraconazole as Palliative Treatment for Proventricular Dilatation Disease in Psittacine Birds
by Laura M. Kleinschmidt, Sharman M. Hoppes, Jeffrey M. B. Musser, Ian Tizard and J. Jill Heatley
Vet. Sci. 2025, 12(5), 459; https://doi.org/10.3390/vetsci12050459 - 12 May 2025
Viewed by 691
Abstract
Proventricular dilatation disease (PDD) is a neurologic syndrome of birds caused by the infectious agent Psittacine Bornavirus (PaBV). Clinical disease may be based on the T-cell-mediated immune response to PaBV within the central and peripheral nervous system, similar to Borna disease virus, a [...] Read more.
Proventricular dilatation disease (PDD) is a neurologic syndrome of birds caused by the infectious agent Psittacine Bornavirus (PaBV). Clinical disease may be based on the T-cell-mediated immune response to PaBV within the central and peripheral nervous system, similar to Borna disease virus, a closely related mammalian virus. Lymphoplasmacytic infiltrations may occur in ganglia, nerve plexuses, peripheral nerves and the central nervous system of the infected bird. Clinical disease may result in multiple neurologic disorders and life-threatening morbidity. Treatment of PDD with antivirals and non-steroidal anti-inflammatories has thus far been non-curative and unsuccessful long-term. Cyclosporine is an immunosuppressant drug that decreases cell-mediated immune responses by inhibiting T-cell proliferation and decreasing cytokine production. In avian species, cyclosporine is a potent immunosuppressant with T-cell-specific action. A pilot study performed in PaBV-infected cockatiels showed increased weight gain and a lack of morbidity or mortality following experimental PaBV infection and cyclosporine treatment at 10 mg/kg orally every 12 h. In this case series of six psittacine birds affected by PDD, cyclosporine at this dose alleviated or reduced clinical signs in multiple birds without severe sequelae. Itraconazole was used concurrently in these cases to prevent secondary fungal infections during immunosuppression but may have had a synergetic effect when used in combination with cyclosporine. Further prospective research is indicated to better evaluate cyclosporine use in birds with PDD. However, these preliminary clinical findings suggest that cyclosporine and itraconazole administration is a treatment option for palliation of PDD in psittacine patients, especially those refractory to other treatments. Full article
(This article belongs to the Section Veterinary Biomedical Sciences)
40 pages, 539 KiB  
Review
α-Mangostin Is a Xanthone Derivative from Mangosteen with Potent Immunomodulatory and Anti-Inflammatory Properties
by Amin F. Majdalawieh, Bayan K. Khatib and Tala M. Terro
Biomolecules 2025, 15(5), 681; https://doi.org/10.3390/biom15050681 - 7 May 2025
Viewed by 1007
Abstract
α-Mangostin, a bioactive xanthone derived from the Garcinia mangostana L. Clusiaceae (G. mangostana) fruit, has demonstrated significant anti-inflammatory and immunomodulatory properties. Chronic inflammation plays a critical role in the pathogenesis of various diseases, including metabolic disorders, autoimmune conditions, and cancer. Conventional [...] Read more.
α-Mangostin, a bioactive xanthone derived from the Garcinia mangostana L. Clusiaceae (G. mangostana) fruit, has demonstrated significant anti-inflammatory and immunomodulatory properties. Chronic inflammation plays a critical role in the pathogenesis of various diseases, including metabolic disorders, autoimmune conditions, and cancer. Conventional anti-inflammatory therapies, such as non-steroidal anti-inflammatory drugs (NSAIDs), often carry undesirable side effects, prompting the need for safer, natural alternatives. This review consolidates the existing literature on the mechanisms by which α-mangostin exerts its anti-inflammatory effects, including the suppression of pro-inflammatory cytokines, modulation of immune cell activity, and inhibition of key signaling pathways such as nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK). Additionally, α-mangostin exhibits immunomodulatory properties by influencing both innate and adaptive immune responses, affecting macrophage polarization, T cell differentiation, and cytokine production. Its efficacy has been observed in numerous disease models, including joint disorders, digestive and metabolic conditions, hepatic diseases, neurological disorders, and respiratory ailments. The potential therapeutic applications of α-mangostin as an anti-inflammatory agent warrant further investigation through preclinical and clinical studies to validate its efficacy and safety. Full article
(This article belongs to the Section Natural and Bio-derived Molecules)
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26 pages, 515 KiB  
Systematic Review
GLP-1R Agonists and Their Therapeutic Potential in Inflammatory Bowel Disease and Other Immune-Mediated Inflammatory Diseases, a Systematic Review of the Literature
by Lena Thin and Wei Ling Teh
Biomedicines 2025, 13(5), 1128; https://doi.org/10.3390/biomedicines13051128 - 6 May 2025
Viewed by 2153
Abstract
Background/Objectives: GLP-1 receptor agonists (GLP-1RAs) have revolutionized weight loss and shown anti-inflammatory actions in several experimental models of colitis. There has been a wealth of recent data suggesting that GLP-1RA treatment may modify disease outcomes in inflammatory bowel disease (IBD). The aim of [...] Read more.
Background/Objectives: GLP-1 receptor agonists (GLP-1RAs) have revolutionized weight loss and shown anti-inflammatory actions in several experimental models of colitis. There has been a wealth of recent data suggesting that GLP-1RA treatment may modify disease outcomes in inflammatory bowel disease (IBD). The aim of this systematic review is to determine if GLP-1RAs can act as a sole or adjunctive agent to induce steroid-free clinical remission in IBD patients. Methods: The PubMed/Medline, Cochrane Clinical Trial, and EMBASE databases were interrogated with a pre-defined search strategy and eligibility criteria to examine the evidence regarding GLP-1RAs’ use in IBD and non-IBD immune-mediated inflammatory disease (IMID) patients. Results: While there is a wealth of pre-clinical animal data suggesting that GLP-1RAs can ameliorate experimental colitis, there is a lack of prospective clinical studies on treating active IBD with GLP-1RAs to specifically induce steroid-free clinical remission. Surrogate data on better IBD composite outcomes have been reported with the use of GLP-1RAs, including a lower risk of surgery, hospitalization, corticosteroid use, and/or the initiation of advance therapies. Data from non-IBD IMID patients are only available for the effect of these agonists on psoriatic plaques, with positive signals. Conclusions: The current evidence for the role of GLP-1RAs as a potential anti-inflammatory therapy in IBD is limited, but provides the impetus for much-needed prospective studies and RCTs that include patients with active IBD. Full article
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26 pages, 1152 KiB  
Review
Juvenile Spondyloarthropathies: Diagnostic and Therapeutic Advances—A Narrative Review
by Călin Lazăr, Mirela Crișan, Oana-Iulia Man, Lucia Maria Sur, Gabriel Samașca and Alexandru Cristian Bolunduț
J. Clin. Med. 2025, 14(9), 3166; https://doi.org/10.3390/jcm14093166 - 3 May 2025
Viewed by 743
Abstract
Spondyloarthropathies (SpAs) represent a diverse group of seronegative immune-mediated inflammatory diseases characterized by a genetic predisposition and an association with human leukocyte antigen-B27. This narrative review aims to explore juvenile spondyloarthropathies (JSpAs), their classification, clinical manifestations, diagnostic challenges, and contemporary treatment strategies. According [...] Read more.
Spondyloarthropathies (SpAs) represent a diverse group of seronegative immune-mediated inflammatory diseases characterized by a genetic predisposition and an association with human leukocyte antigen-B27. This narrative review aims to explore juvenile spondyloarthropathies (JSpAs), their classification, clinical manifestations, diagnostic challenges, and contemporary treatment strategies. According to the International League of Associations for Rheumatology criteria, JSpAs include several specific forms: enthesitis-related arthritis, psoriatic arthritis, and undifferentiated arthritis. Despite established classifications, the terms and definitions surrounding these conditions can often lead to confusion among healthcare professionals. This ambiguity underscores the need for a standardized approach to nosological classification. The clinical presentation of JSpAs can be multifaceted, encompassing both articular and extra-articular manifestations. Articular symptoms may include enthesitis and varying forms of arthritis, while extra-articular involvement can range from uveitis to gastrointestinal, cardiovascular, pulmonary, neurological, and renal complications. These diverse manifestations highlight the systemic nature of the disease and the importance of a holistic approach to diagnosis and treatment. While laboratory tests for SpAs are often non-specific, imaging modalities such as musculoskeletal ultrasound and magnetic resonance imaging play a crucial role in the early detection of inflammatory lesions. These imaging techniques can provide valuable insights into disease progression and aid in the formulation of appropriate treatment plans. Current treatment guidelines advocate for a “stepwise” approach to therapy, beginning with nonsteroidal anti-inflammatory drugs and progressing to glucocorticoids, disease-modifying antirheumatic drugs, and biological agents, particularly anti-tumor necrosis factor alpha agents. The primary objective of treatment is to achieve clinical remission or, at a minimum, to attain low disease activity. Regular monitoring of disease activity is imperative; however, the lack of validated assessment tools for the pediatric population remains a significant challenge. JSpAs pose unique challenges in terms of diagnosis and management due to their diverse manifestations and the complexities of their classification. Ongoing research and clinical efforts are essential to refine our understanding of these conditions, improve treatment outcomes, and enhance quality of life for affected children and their families. Effective management hinges on early detection, individualized treatment plans, and continuous monitoring, ensuring that patients receive the most appropriate care tailored to their specific needs. Full article
(This article belongs to the Section Clinical Pediatrics)
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38 pages, 8552 KiB  
Review
Enzyme-Based Anti-Inflammatory Therapeutics for Inflammatory Diseases
by Kannan Badri Narayanan
Pharmaceutics 2025, 17(5), 606; https://doi.org/10.3390/pharmaceutics17050606 - 2 May 2025
Cited by 1 | Viewed by 3107
Abstract
Inflammation is a multifaceted biological response of the immune system against various harmful stimuli, including pathogens (such as bacteria and viruses), cellular damage, toxins, and natural/synthetic irritants. This protective mechanism is essential for eliminating the cause of injury, removing damaged cells, and initiating [...] Read more.
Inflammation is a multifaceted biological response of the immune system against various harmful stimuli, including pathogens (such as bacteria and viruses), cellular damage, toxins, and natural/synthetic irritants. This protective mechanism is essential for eliminating the cause of injury, removing damaged cells, and initiating the repair process. While inflammation is a fundamental component of the body’s defense and healing process, its dysregulation can lead to pathological consequences, contributing to various acute and chronic diseases, such as autoimmune disorders, cancer, metabolic syndromes, cardiovascular diseases, neurodegenerative conditions, and other systemic complications. Generally, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease-modifying anti-rheumatic drugs (DMARDs), antihistamines, biologics, and colchicine are used as pharmacological agents in the management of inflammatory diseases. However, these conventional treatments often have limitations, including adverse side effects, long-term toxicity, and drug resistance. In contrast, enzyme-based therapeutics have emerged as a promising alternative due to their high specificity, catalytic efficiency, and ability to modulate inflammatory pathways with reduced side effects. These enzymes function by scavenging reactive oxygen species (ROS), inhibiting cytokine transcription, degrading circulating cytokines, and blocking cytokine release by targeting exocytosis-related receptors. Additionally, their role in tissue repair and regeneration further enhances their therapeutic potential. Most natural anti-inflammatory enzymes belong to the oxidoreductase class, including catalase and superoxide dismutase, as well as hydrolases such as trypsin, chymotrypsin, nattokinase, bromelain, papain, serratiopeptidase, collagenase, hyaluronidase, and lysozyme. Engineered enzymes, such as Tobacco Etch Virus (TEV) protease and botulinum neurotoxin type A (BoNT/A), have also demonstrated significant potential in targeted anti-inflammatory therapies. Recent advancements in enzyme engineering, nanotechnology-based enzyme delivery, and biopharmaceutical formulations have further expanded their applicability in treating inflammatory diseases. This review provides a comprehensive overview of both natural and engineered enzymes, along with their formulations, used as anti-inflammatory therapeutics. It highlights improvements in stability, efficacy, and specificity, as well as minimized immunogenicity, while discussing their mechanisms of action and clinical applications and potential future developments in enzyme-based biomedical therapeutics. Full article
(This article belongs to the Special Issue Medical Applications of Biologic Drugs)
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13 pages, 593 KiB  
Article
Ketoprofen Lysine Salt Versus Corticosteroids in Early Outpatient Management of Mild and Moderate COVID-19: A Retrospective Study
by Domenica Francesca Mariniello, Raffaella Pagliaro, Vito D’Agnano, Angela Schiattarella, Fabio Perrotta and Andrea Bianco
Pharmacy 2025, 13(3), 65; https://doi.org/10.3390/pharmacy13030065 - 1 May 2025
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Abstract
Background: Accelerating recovery and preventing the progression to more severe outcomes for patients with coronavirus disease 2019 (COVID-19) is of paramount importance. Non-steroidal anti-inflammatory agents (NSAIDs) have been widely adopted in the international recommendations for non-severe COVID-19 management. Among NSAIDs, evidence about the [...] Read more.
Background: Accelerating recovery and preventing the progression to more severe outcomes for patients with coronavirus disease 2019 (COVID-19) is of paramount importance. Non-steroidal anti-inflammatory agents (NSAIDs) have been widely adopted in the international recommendations for non-severe COVID-19 management. Among NSAIDs, evidence about the efficacy of ketoprofen lysin salt (KLS) in the treatment of non-severe COVID-19 has not been reported. Methods: This retrospective study compared the outcomes of 120 patients with mild to moderate COVID-19 treated at home with KLS between March 2021 and May 2023 compared with the outcomes of 165 patients who received corticosteroids. The outcomes included hospitalization, the need for oxygen supplementation, clinical recovery from acute COVID-19, and time to negative swabs. Results: Symptoms persisted in a lower percentage of patients in the KLS group compared to the corticosteroids group (p < 0.0001) and for a shorter period (p = 0.046). We found 6 patients (5%) in the KLS group were hospitalized compared to 45 (27%) in the corticosteroids group (p < 0.001). A higher percentage of patients in the corticosteroids group require oxygen administration (p < 0.001). In addition, patients taking corticosteroids showed a longer viral shedding period compared to those taking KLS (p = 0.004). A final multivariate analysis suggests that KLS might reduce hospitalization risk, the need for oxygen supplementation, and the persistence of post-COVID-19 symptoms when compared to an oral corticosteroid after adjusting for significant co-variables. Conclusions: KLS might have a positive effect on clinical recovery in non-severe COVID-19 patients. A comparison with other NSAIDs in terms of difference in efficacy and safety should be investigated in further trials. Full article
(This article belongs to the Collection New Insights into Pharmacy Teaching and Learning during COVID-19)
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