Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Article Types

Countries / Regions

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Search Results (2,211)

Search Parameters:
Keywords = non-steroidal

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
27 pages, 796 KB  
Review
Beyond Antibiotics: Repurposing Non-Antibiotic Drugs as Novel Antibacterial Agents to Combat Resistance
by Gagan Tiwana, Ian Edwin Cock, Stephen Maxwell Taylor and Matthew James Cheesman
Int. J. Mol. Sci. 2025, 26(20), 9880; https://doi.org/10.3390/ijms26209880 - 10 Oct 2025
Abstract
The escalating global threat of antimicrobial resistance (AMR) necessitates innovative therapeutic strategies beyond traditional antibiotic development. Drug repurposing offers a rapid, cost-effective approach by identifying new antibacterial applications for existing non-antibiotic drugs with established safety profiles. Emerging evidence indicates that diverse classes of [...] Read more.
The escalating global threat of antimicrobial resistance (AMR) necessitates innovative therapeutic strategies beyond traditional antibiotic development. Drug repurposing offers a rapid, cost-effective approach by identifying new antibacterial applications for existing non-antibiotic drugs with established safety profiles. Emerging evidence indicates that diverse classes of non-antibiotic drugs, including non-steroidal anti-inflammatory drugs (NSAIDs), statins, antipsychotics, calcium channel blockers and antidepressants, exhibit intrinsic antibacterial activity, or potentiate antibiotic efficacy. This review critically explores the mechanisms by which drugs that are not recognised as antibiotics exert antibacterial effects, including efflux pump inhibition, membrane disruption, biofilm inhibition, and quorum sensing interference. We discuss specific examples that demonstrate reductions in minimum inhibitory concentrations (MICs) of antibiotics when combined with these drugs, underscoring their potential as antibiotic adjuvants. Furthermore, we examine pharmacokinetic considerations, toxicity challenges, and clinical feasibility for repurposing these agents as standalone antibacterials or in combination therapies. Finally, we highlight future directions, including the integration of artificial intelligence and machine learning to prioritise drug candidates for repurposing, and the development of targeted delivery systems to enhance bacterial selectivity while minimising host toxicity. By exploring the overlooked potential of non-antibiotic drugs, this review seeks to stimulate translational research aimed at leveraging these agents in combating resistant bacterial infections. Nonetheless, it is crucial to acknowledge that such drugs may also pose unintended risks, including gut microbiota disruption and facilitation of resistance development. Hence, future research should pursue these opportunities with equal emphasis on efficacy, safety, and resistance mitigation. Full article
(This article belongs to the Collection Latest Review Papers in Molecular Microbiology)
Show Figures

Figure 1

10 pages, 382 KB  
Article
The Relationship Between Refeeding Syndrome and Preterm Morbidities in Preterm Infants
by Aybuke Yazici, Ipek Guney Varal, Gaffari Tunc, Onur Bagci and Ayse Oren
Children 2025, 12(10), 1370; https://doi.org/10.3390/children12101370 - 10 Oct 2025
Abstract
Objective: This study was conducted to determine the risk factors for refeeding syndrome (RFS) in preterm infants and evaluate its relationship with preterm morbidities. Methods: Preterm infants born before 30 weeks of gestation were retrospectively evaluated. RFS was diagnosed as phosphorus [...] Read more.
Objective: This study was conducted to determine the risk factors for refeeding syndrome (RFS) in preterm infants and evaluate its relationship with preterm morbidities. Methods: Preterm infants born before 30 weeks of gestation were retrospectively evaluated. RFS was diagnosed as phosphorus <4 mg/dL and/or calcium >11 mg/dL on postnatal day 7. Demographic and clinical findings were compared between preterm infants with and without RFS. Results: A total of 174 infants who met the inclusion criteria were analyzed. RFS was diagnosed with 60 infants (34.5%). The mean gestational age (GA) was 27 (range, 25–28) weeks in the RFS group and 28 (range, 26–30) weeks in the non-RFS group (p = 0.038). Mean birth weight (BW) in each group was 790 (range, 630–1000) grams and 1033 (range, 800–1310) grams, respectively (p < 0.001). The RFS group had a lower rate of antenatal steroid (ANS) administration, lower APGAR, length of hospital stay, and higher rates of small for gestational age status, respiratory distress syndrome (RDS), bronchopulmonary dysplasia, and patent ductus arteriosus (p < 0.05). On postnatal day 7, the RFS group had lower phosphorus and higher calcium levels (p < 0.001). After adjustment for GA, BW, Apgar score, and ANS, the frequency of RDS was higher among infants with RFS (p < 0.05). Conclusions: Preterm infants with RDS were more likely to develop RFS. Our results suggest that these infants require more frequent laboratory testing and closer follow-up to monitor for RFS and ensure timely electrolyte support. Full article
(This article belongs to the Section Pediatric Neonatology)
Show Figures

Figure 1

19 pages, 718 KB  
Review
Hydrogel-Based Formulations to Deliver Analgesic Drugs: A Scoping Review of Applications and Efficacy
by Sveva Di Franco, Aniello Alfieri, Pasquale Sansone, Vincenzo Pota, Francesco Coppolino, Andrea Frangiosa, Vincenzo Maffei, Maria Caterina Pace, Maria Beatrice Passavanti and Marco Fiore
Biomedicines 2025, 13(10), 2465; https://doi.org/10.3390/biomedicines13102465 - 10 Oct 2025
Abstract
Background/Objectives:Hydrogels are highly hydrated, biocompatible polymer networks increasingly investigated as drug-delivery systems (DDS) for analgesics. Their ability to modulate local release, prolong drug residence time, and reduce systemic toxicity positions them as promising platforms in perioperative, chronic, and localized pain settings. This [...] Read more.
Background/Objectives:Hydrogels are highly hydrated, biocompatible polymer networks increasingly investigated as drug-delivery systems (DDS) for analgesics. Their ability to modulate local release, prolong drug residence time, and reduce systemic toxicity positions them as promising platforms in perioperative, chronic, and localized pain settings. This scoping review aimed to systematically map clinical applications, efficacy, and safety of hydrogel-based DDS for analgesics, while also documenting non-DDS uses where the matrix itself contributes to pain modulation through physical mechanisms. Methods: Following PRISMA-ScR guidance, PubMed, Embase, and Cochrane databases were searched without publication date restrictions. Only peer-reviewed clinical studies were included; preclinical studies and non-journal literature were excluded. Screening and selection were performed in duplicate. Data extracted included drug class, hydrogel technology, clinical setting, outcomes, and safety. Protocol was registered with Open Science Framework. Results: A total of 26 clinical studies evaluating hydrogel formulations as DDS for analgesics were included. Most were randomized controlled trials, spanning 1996–2024. Local anesthetics were the most frequent drug class, followed by opioids, corticosteroids, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), and neuromodulators. Application sites were predominantly topical/transdermal and perioperative/incisional. Across the DDS cohort, most of the studies reported improved analgesic outcomes, including reduced pain scores and lower rescue medication use; neutral or unclear results were rare. Safety reporting was limited, but tolerability was generally favorable. Additionally, 38 non-DDS studies demonstrated pain reduction through hydrogel-mediated cooling, lubrication, or barrier effects, particularly in burns, ocular surface disorders, and discogenic pain. Conclusions: Hydrogel-based DDS for analgesics show consistent clinical signals of benefit across diverse contexts, aligning with their mechanistic rationale. While current evidence supports their role as effective, well-tolerated platforms, translational gaps remain, particularly for hybrid nanotechnology systems and standardized safety reporting. Non-DDS applications confirm the intrinsic analgesic potential of hydrogel matrices, underscoring their relevance in multimodal pain management strategies. Full article
13 pages, 1079 KB  
Article
Transpancreatic Sphincterotomy Is a Safe and Effective Pancreatic Guidewire-Assisted Cannulation Method: Real-World Data Analysis of the Hungarian ERCP Registry
by Dániel Pécsi, Nelli Farkas, Szilárd Gódi, Péter Hegyi, Andrea Szentesi, István Altorjay, Tamás Bakucz, Ákos Orbán-Szilágyi, Zoltán Szepes, László Czakó, Árpád Patai, Tibor Gyökeres, Roland Fejes, Zsolt Dubravcsik and Áron Vincze
J. Clin. Med. 2025, 14(19), 7118; https://doi.org/10.3390/jcm14197118 - 9 Oct 2025
Abstract
Background/Objectives: Difficult biliary cannulation during endoscopic retrograde cholangiopancreatography (ERCP) poses significant challenges and increases the risk of adverse events. Pancreatic guidewire (PGW)-assisted techniques offer potential solutions, but real-world comparative data are limited. Methods: This cohort study of prospectively collected data analyzed 234 ERCP [...] Read more.
Background/Objectives: Difficult biliary cannulation during endoscopic retrograde cholangiopancreatography (ERCP) poses significant challenges and increases the risk of adverse events. Pancreatic guidewire (PGW)-assisted techniques offer potential solutions, but real-world comparative data are limited. Methods: This cohort study of prospectively collected data analyzed 234 ERCP cases from the Hungarian ERCP Registry, focusing on three PGW-assisted methods: transpancreatic sphincterotomy (TPS), double-guidewire technique (DGW), and prophylactic pancreatic stent-assisted cannulation (PPS-C). Results: TPS demonstrated the highest primary cannulation success rate (83.1%), significantly outperforming DGW (67.7%) and PPS-C (67.6%) (p < 0.001). With salvage methods, cannulation success was high across all groups. Post-ERCP pancreatitis rates were low (5.0% TPS, 5.6% DGW, 3.9% PPS-C), but prophylactic measures (pancreatic stents, indomethacin) were underutilized. Conclusions: Our findings suggest that TPS is a safe and effective alternative for difficult biliary cannulation in ERCP. Routine considerations of post-ERCP pancreatitis prophylaxis (prophylactic pancreatic stents and non-steroidal suppositories) are recommended in all PGW-assisted cannulations to minimize complications. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
Show Figures

Figure 1

28 pages, 2360 KB  
Article
Cobalt(II) Complexes of 4′-Bromo-Fenamic Acid: Antioxidant Properties, Antibacterial Activity, and Interaction with DNA and Albumins
by Georgios Malis, Christina N. Banti, Alexia Tialiou, Michael R. Reithofer, Antonios G. Hatzidimitriou, Sotiris K. Hadjikakou, Konstantina C. Fylaktakidou and George Psomas
Int. J. Mol. Sci. 2025, 26(19), 9787; https://doi.org/10.3390/ijms26199787 - 8 Oct 2025
Viewed by 228
Abstract
The reaction of 4′–bromo-fenamic acid, a bromo-derivative of fenamic acid (the scaffold of the fenamate non-steroidal anti-inflammatory drugs), with Co(II) in the absence or presence of various nitrogen-donor ligands yielded nine novel, neutral mononuclear Co(II) complexes. These complexes were characterized by physicochemical and [...] Read more.
The reaction of 4′–bromo-fenamic acid, a bromo-derivative of fenamic acid (the scaffold of the fenamate non-steroidal anti-inflammatory drugs), with Co(II) in the absence or presence of various nitrogen-donor ligands yielded nine novel, neutral mononuclear Co(II) complexes. These complexes were characterized by physicochemical and spectroscopic techniques and single-crystal X-ray crystallography. The biological evaluation of the compounds focused on their antioxidant and antimicrobial efficacy, as well as their interaction with calf-thymus DNA, pBR322 plasmid DNA (in the absence or presence of diverse irradiations) and serum albumins. The complexes have shown significant antioxidant activity since they can scavenge 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radicals (up to 96.48 ± 0.07%) and reduce H2O2 (up to 96.93 ± 0.53%). Antimicrobial testing revealed that the complexes were more active than free 4′-bromo-fenamic acid with four of them classified as bactericidal agents against selected bacterial strains. The compounds can interact with calf-thymus DNA via intercalation, and the calculated DNA-binding constants are on the 106 M−1 order. The plasmid DNA-cleavage ability of the compounds is strongly enhanced under UVA irradiation (photocleavage > 90%). In addition, the compounds can bind tightly and reversibly to serum albumins with binding constants in the 105 M−1 range. Full article
(This article belongs to the Special Issue Focus on Antioxidants and Human Diseases)
Show Figures

Figure 1

33 pages, 781 KB  
Review
Recent Advances in Electrochemical Sensors for the Detection of Anti-Inflammatory and Antibiotic Drugs: A Comprehensive Review
by Gisele Afonso Bento Mello, Stephen Rathinaraj Benjamin, Fábio de Lima and Rosa F. Dutra
Biosensors 2025, 15(10), 676; https://doi.org/10.3390/bios15100676 - 8 Oct 2025
Viewed by 268
Abstract
Electrochemical sensors have emerged as powerful analytical tools for the detection of anti-inflammatory and antibiotic drugs due to their high sensitivity, rapid response, and cost-effectiveness compared to conventional chromatographic and spectrophotometric methods. This review highlights recent advances in electrode materials, surface modification strategies, [...] Read more.
Electrochemical sensors have emerged as powerful analytical tools for the detection of anti-inflammatory and antibiotic drugs due to their high sensitivity, rapid response, and cost-effectiveness compared to conventional chromatographic and spectrophotometric methods. This review highlights recent advances in electrode materials, surface modification strategies, and signal amplification approaches for quantifying nonsteroidal anti-inflammatory drugs (NSAIDs) and various antibiotic classes, including sulfonamides, tetracyclines, macrolides, and quinolones. Particular attention is given to nanostructured carbon-based materials, metal nanoparticles, and polymer composites that enhance electron transfer, improve selectivity, and lower limits of detection (LODs). The analytical performance of different electrochemical techniques such as cyclic voltammetry, differential pulse voltammetry, and square-wave voltammetry is critically compared across various drug targets. Trends indicate that hybrid nanomaterial-modified electrodes consistently achieve sub-micromolar detection limits in biological and environmental samples, offering potential for point-of-care diagnostics and environmental monitoring. Current challenges include improving sensor stability, mitigating fouling effects, and ensuring reproducibility in complex matrices. Future research should focus on integrated, miniaturized sensing platforms capable of multiplex detection, paving the way for rapid, portable, and sustainable analytical solutions in pharmaceutical and biomedical applications. Full article
Show Figures

Graphical abstract

13 pages, 872 KB  
Article
Corticosteroid Use and Recurrence Risk Factors in Granulomatous Mastitis: A 17-Year Saudi Arabian Cohort Study—Steroids in Granulomatous Mastitis
by Shoag J. Albugami, Rema F. AlRasheed, Hussam A. Alharbi, Sarah S. Alobaid, Hawazin S. Alqahtani, Mays N. Alharbi, Eyad AlKharashi and Khalid Alhajri
Clin. Pract. 2025, 15(10), 185; https://doi.org/10.3390/clinpract15100185 - 6 Oct 2025
Viewed by 183
Abstract
Background: Granulomatous mastitis (GM) is a rare, chronic inflammatory breast condition with poorly understood etiology and variable clinical presentation. The efficacy of corticosteroid therapy in reducing recurrence remains controversial, particularly in Middle Eastern populations where the condition appears more prevalent. This study aimed [...] Read more.
Background: Granulomatous mastitis (GM) is a rare, chronic inflammatory breast condition with poorly understood etiology and variable clinical presentation. The efficacy of corticosteroid therapy in reducing recurrence remains controversial, particularly in Middle Eastern populations where the condition appears more prevalent. This study aimed to describe the demographic and clinical characteristics of patients with GM, evaluate the efficacy of corticosteroid therapy in reducing recurrence rates, and identify risk factors associated with disease recurrence. Methods: A retrospective cohort analysis was conducted on 56 patients diagnosed with GM between 2003 and 2020 at a single tertiary referral center. Patients were stratified into two groups based on steroid use (n = 14 with steroids and n = 42 without steroids). Results: The mean age of the cohort was 46.3 ± 13.2 years, with no significant differences in baseline characteristics between the steroid and non-steroid groups. The most common presentation was a breast mass (32.69%), often associated with abscess formation (25%). Core biopsy was the primary diagnostic tool used (51.79%). Recurrence of GM occurred in 10 patients (18%) overall: 7 patients (17%) in the non-steroid group and 3 patients (21%) in the steroid group. The difference in recurrence rates between the treatment groups was not statistically significant (HR = 1.40, 95% CI:0.30–6.52, p = 0.671). A history of infection (HR = 5.85, 95% CI: 1.60–21.44, p = 0.008) and hormonal disorders (hyperprolactinemia in one patient) (HR = 13.90, 95% CI: 1.43–135.52, p = 0.024) were significantly associated with recurrence. Conclusions: GM remains diagnostically challenging with an 18% recurrence rate in our cohort. We observed no statistically significant reduction in recurrence with corticosteroids, though our analysis was limited by sample size. These findings suggest that targeted management of these conditions may be beneficial in GM patients, though larger multicenter studies are needed to confirm these associations and establish standardized treatment protocols. Full article
Show Figures

Figure 1

12 pages, 342 KB  
Systematic Review
Clinical and Demographic Characteristics of Oral Sarcoidosis: A Systematic Review of Case Reports and Case Series
by Mohamed Jaber, Nadin Abouseif, Mawada Abdelmagied and Essra Mohamed El-Ameen
J. Clin. Med. 2025, 14(19), 7006; https://doi.org/10.3390/jcm14197006 - 3 Oct 2025
Viewed by 202
Abstract
Background/Objectives: Sarcoidosis is a granulomatous disorder of unknown etiology that can affect multiple organs, including the oral cavity. This study aimed to compare the clinical and demographic characteristics of sarcoidosis cases with and without bone involvement in the jaw. Methods: A [...] Read more.
Background/Objectives: Sarcoidosis is a granulomatous disorder of unknown etiology that can affect multiple organs, including the oral cavity. This study aimed to compare the clinical and demographic characteristics of sarcoidosis cases with and without bone involvement in the jaw. Methods: A systematic review of the case reports and case series of sarcoidosis in the oral cavity between 1943 to 2024 were analyzed. Variables assessed included age, sex, presenting symptoms, duration of symptoms, diagnosis methodology, treatment approaches, and outcomes. Results: A total of 59 studies reporting 77 patients were included, with a mean age of 43.3 yrs. Female predominance was noted in both, bone-involved (61.5%) and non-bone-involvement cases (72.5%). Patients with bone involvement often presented with localized symptoms such as loose teeth (34.6%), bone loss (69.2%), and nasal obstruction (15.4%), whereas non-bone-involvement cases frequently exhibited soft tissue manifestations, like swelling (38%) and bleeding (14%). Treatment typically involved surgical intervention and steroid therapy in both groups, with favorable outcomes achieved in most cases. Conclusions: This systematic review presents the most extensive analysis of oral sarcoidosis. Oral sarcoidosis presents as two distinct clinical entities based on bone involvement. Soft tissue lesions often serve as an early diagnostic clue for systemic disease, while bony manifestations suggest a later, more destructive complication. Recognizing this dichotomy is crucial for dentists and clinicians to ensure timely diagnosis and appropriate referral, and this underscores the oral cavity’s critical role as an indicator of systemic illness and mandates a multidisciplinary management strategy. Full article
(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)
Show Figures

Figure 1

40 pages, 3660 KB  
Review
Anti-Inflammatory Activity of 1,2-Benzothiazine 1,1-Dioxide Derivatives
by Berenika M. Szczęśniak-Sięga and Izabela Topolska
Pharmaceuticals 2025, 18(10), 1484; https://doi.org/10.3390/ph18101484 - 2 Oct 2025
Viewed by 300
Abstract
There is an urgent need to develop new anti-inflammatory compounds due to the versatility of their applications and the side effects associated with currently used nonsteroidal anti-inflammatory drugs (NSAIDs). Compounds containing the 1,2-benzothiazine 1,1-dioxide moiety in their structure have demonstrated a broad range [...] Read more.
There is an urgent need to develop new anti-inflammatory compounds due to the versatility of their applications and the side effects associated with currently used nonsteroidal anti-inflammatory drugs (NSAIDs). Compounds containing the 1,2-benzothiazine 1,1-dioxide moiety in their structure have demonstrated a broad range of pharmacological activities, among which the anti-inflammatory effect is the most well-documented. Numerous in vivo studies have confirmed the effectiveness of these compounds in alleviating pain and inflammation. In turn, in vitro studies have shown that 1,2-benzothiazine derivatives exhibit anti-inflammatory activity not only through the classical mechanism involving the inhibition of cyclooxygenase (COX) but also through modern, more complex mechanisms. These innovative mechanisms include inhibition of microsomal prostaglandin E2 synthase-1 (mPGES-1) or 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), suppression of pro-inflammatory cytokines, and modulation of kinase activity involved in inflammatory processes. Importantly, many studies have shown that some new 1,2-benzothiazine 1,1-dioxide derivatives exhibit even stronger anti-inflammatory activity than traditional NSAIDs, making them promising candidates for new drugs targeting inflammation-related diseases. This paper presents a review of 1,2-benzothiazine 1,1-dioxide derivatives investigated for their anti-inflammatory activity in both in vivo and in vitro models, taking into account their various mechanisms of action and potential directions for further research. Full article
Show Figures

Graphical abstract

16 pages, 616 KB  
Review
Oxygen–Ozone Therapy in Tendinopathy Management: A Comprehensive Review
by Giacomo Farì, Giovanni Pignatelli, Sara Clelia Longo, Fabrizio Brindisino, Giuseppe Giovannico, Simone Della Tommasa, Laura Dell’Anna, Luisa De Palma, Francesco Quarta and Andrea Bernetti
J. Pers. Med. 2025, 15(10), 459; https://doi.org/10.3390/jpm15100459 - 30 Sep 2025
Viewed by 369
Abstract
Background: Tendinopathy is a degenerative condition caused by mechanical overload, accounting for approximately 30% of musculoskeletal healthcare cases. It progresses through a process characterized by collagen disorganization, altered vascularization, and neuronal ingrowth. Traditional conservative treatments, such as therapeutic exercises, non-steroidal anti-inflammatory drugs, [...] Read more.
Background: Tendinopathy is a degenerative condition caused by mechanical overload, accounting for approximately 30% of musculoskeletal healthcare cases. It progresses through a process characterized by collagen disorganization, altered vascularization, and neuronal ingrowth. Traditional conservative treatments, such as therapeutic exercises, non-steroidal anti-inflammatory drugs, and physical therapies, are useful, but their effectiveness is sometimes only partial and there is a need to search for new potential solutions. Recent interest in oxygen–ozone (O2-O3) therapy stems from preliminary observations suggesting potential anti-inflammatory and regenerative effects. Nevertheless, its clinical role remains speculative and warrants thorough investigation beyond anecdotal evidence. Considering the heterogeneity of clinical presentations and treatment responses among patients, O2-O3 therapy has been proposed as a promising tool for tailoring personalized treatment strategies for tendinopathy. This review critically appraises the available literature concerning the mechanistic rationale and clinical applications of O2-O3 therapy in tendinopathy, with attention to both its theoretical underpinnings and the quality of empirical evidence. Methods: A literature search was conducted on O2-O3 therapy for tendinopathy using PubMed, Cochrane, and Embase, filtering for full-text articles published between 2004 and 2024. Recent clinical trials were included irrespective of evidence level, while excluding systematic reviews, duplicates, and irrelevant studies. Results: Ozone has been shown to modulate oxidative stress, promote neovascularization, and suppress pro-inflammatory cytokines. Both clinical and in vivo studies indicate that O2-O3 therapy relieves pain, enhances tendon healing, and improves biomechanical properties. Some comparative studies suggest that O2-O3 therapy might provide more sustained symptoms control than corticosteroids, but the heterogeneity of follow-up durations and outcome measures prevents definitive conclusions. Conclusions: O2-O3 therapy emerges as a potentially valuable adjunct in the management of chronic tendinopathy, particularly in cases unresponsive to conventional treatments. However, its clinical role remains to be clearly defined and its possible role in personalized medicine needs further exploration, particularly in relation to patient stratification and individualized treatment protocols. Further high-quality randomized controlled trials are warranted to validate its efficacy, determine long-term outcomes, and standardize treatment protocols to ensure safety and reproducibility. Full article
Show Figures

Figure 1

26 pages, 2093 KB  
Article
Preclinical Evaluation of the Efficacy of α-Difluoromethylornithine and Sulindac Against SARS-CoV-2 Infection
by Natalia A. Ignatenko, Hien T. Trinh, April M. Wagner, Eugene W. Gerner, Christian Bime, Chiu-Hsieh Hsu and David G. Besselsen
Viruses 2025, 17(10), 1306; https://doi.org/10.3390/v17101306 - 26 Sep 2025
Viewed by 390
Abstract
Despite numerous research efforts and several effective vaccines and therapies developed against coronavirus disease 2019 (COVID-19), drug repurposing remains an attractive alternative approach for treatment of SARS-CoV-2 variants and other viral infections that may emerge in the future. Cellular polyamines support viral propagation [...] Read more.
Despite numerous research efforts and several effective vaccines and therapies developed against coronavirus disease 2019 (COVID-19), drug repurposing remains an attractive alternative approach for treatment of SARS-CoV-2 variants and other viral infections that may emerge in the future. Cellular polyamines support viral propagation and tumor growth. Here we tested the antiviral activity of two polyamine metabolism-targeting drugs, an irreversible inhibitor of polyamine biosynthesis, α-difluoromethylornithine (DFMO), and a non-steroidal anti-inflammatory drug (NSAID), Sulindac, which have been previously evaluated for colon cancer chemoprevention. The drugs were tested as single agents and in combination in the human Calu-3 lung adenocarcinoma and Caco-2 colon adenocarcinoma cell lines and the K18-hACE2 transgenic mouse model of severe COVID-19. In the infected human cell lines, the DFMO/Sulindac combination significantly suppressed SARS-CoV-2 N1 Nucleocapsid mRNA by interacting synergistically when cells were pretreated with drugs and additively when treatment was applied to the infected cells. The Sulindac alone and DFMO/Sulindac combination treatments also suppressed the expression of the viral Spike protein and the host angiotensin-converting enzyme 2 (ACE2). In K18-hACE2 mice, the antiviral activity of DFMO and Sulindac as single agents and in combination was tested as prophylaxis (drug supplementation started 7 days before infection) or as treatment (drug supplementation started 24 h post-infection) at the doses equivalent to patient chemoprevention trials (835 ppm DFMO and 167 ppm Sulindac). The drugs’ antiviral activity in vivo was evaluated by measuring the clinical (survival rates and clinical scores), viral (viral load and virus infectivity), and biochemical (plasma polyamine, Sulindac, and Sulindac metabolite levels) endpoints. Prophylaxis with DFMO and Sulindac as single agents significantly increased survival rates in the young male mice (p = 0.01 and p = 0.027, respectively), and the combination was effective in the aged male mice (p = 0.042). Young female mice benefited the most from the prophylaxis with Sulindac alone (p = 0.001) and the DFMO/Sulindac combination (p = 0.018), while aged female mice did not benefit significantly from any intervention. Treatment of SARS-CoV-2-infected animals with DFMO or/and Sulindac did not significantly improve their survival rates. Overall, our studies demonstrated that DFMO and Sulindac administration as the prophylaxis regimen provided strong protection against the lethal outcome of SARS-CoV-2 infection and that male mice benefited more from the polyamine-targeted antiviral treatment than female mice. Our findings underscore the importance of evaluation of the antiviral activity of the drugs in the context of sex and age. Full article
(This article belongs to the Section Coronaviruses)
Show Figures

Graphical abstract

27 pages, 1325 KB  
Systematic Review
Sustained-Release Oral Delivery of NSAIDs and Acetaminophen: Advances and Recent Formulation Strategies—A Systematic Review
by Paulina Drapińska, Katarzyna Skulmowska-Polok, Joanna Chałupka and Adam Sikora
Pharmaceutics 2025, 17(10), 1264; https://doi.org/10.3390/pharmaceutics17101264 - 26 Sep 2025
Viewed by 594
Abstract
Background: Sustained-release (SR) formulations of non-steroidal anti-inflammatory drugs (NSAIDs) aim to prolong therapeutic activity, reduce dosing frequency, and improve patient adherence. However, currently marketed SR NSAIDs exhibit persistent limitations, including incomplete control over release kinetics, high interpatient variability in bioavailability, limited reduction [...] Read more.
Background: Sustained-release (SR) formulations of non-steroidal anti-inflammatory drugs (NSAIDs) aim to prolong therapeutic activity, reduce dosing frequency, and improve patient adherence. However, currently marketed SR NSAIDs exhibit persistent limitations, including incomplete control over release kinetics, high interpatient variability in bioavailability, limited reduction in gastrointestinal adverse effects, and insufficient dose flexibility for individualized therapy. In many cases, conventional excipients and release mechanisms remain predominant, leaving drug-specific physicochemical and pharmacokinetic constraints only partially addressed. These gaps highlight the need for a comprehensive synthesis of recent technological advances to guide the development of more effective, patient-centered delivery systems. Methods: A narrative literature review was conducted using Web of Science and PubMed databases to identify original research articles and comprehensive technological studies on oral SR formulations of NSAIDs and paracetamol published between January 2020 and March 2025. Inclusion criteria focused on preclinical and technological research addressing formulation design, excipient innovations, and manufacturing approaches. Results: Sixty-four studies met the inclusion criteria, encompassing polymeric matrices (31%), lipid-based carriers (18%), microspheres/hydrogel beads/interpenetrating polymer networks (30%), nanostructured systems (11%), and hybrid platforms (10%). The most common strategies involved pH-dependent release, mucoadhesive systems, and floating drug delivery, aiming to optimize release kinetics, minimize mucosal irritation, and sustain therapeutic plasma levels. Advances in manufacturing—such as hot-melt extrusion, 3D printing, electrospinning, and spray drying—enabled enhanced control of drug release profiles, improved stability, and in some cases up to 30–50% prolongation of release time or reduction in Cmax fluctuations compared with conventional formulations. Conclusions: Recent formulation strategies show substantial potential to overcome long-standing limitations of SR NSAID delivery, with expected benefits for patient compliance and quality of life through reduced dosing frequency, better tolerability, and more predictable therapeutic effects. Nevertheless, integration of in vitro performance with pharmacokinetic and clinical safety outcomes remains limited, and the translation to clinical practice is still in its early stages. This review provides a comprehensive overview of current technological trends, identifies persisting gaps, and proposes future research directions to advance SR NSAID systems toward safer, more effective, and patient-focused therapy. Full article
Show Figures

Graphical abstract

15 pages, 963 KB  
Review
Immunosuppressive Therapies in Pulmonary Sarcoidosis: A Practical, Evidence-Based Review
by Zehra Dhanani and Rohit Gupta
J. Clin. Med. 2025, 14(19), 6828; https://doi.org/10.3390/jcm14196828 - 26 Sep 2025
Viewed by 770
Abstract
Sarcoidosis is a chronic inflammatory disease of unknown etiology that can involve virtually any organ, with pulmonary involvement seen in over 90% of cases. Although many patients experience spontaneous remission, approximately 10–30% develop progressive pulmonary disease, which may lead to fibrocystic changes, respiratory [...] Read more.
Sarcoidosis is a chronic inflammatory disease of unknown etiology that can involve virtually any organ, with pulmonary involvement seen in over 90% of cases. Although many patients experience spontaneous remission, approximately 10–30% develop progressive pulmonary disease, which may lead to fibrocystic changes, respiratory failure, and death. Oral glucocorticoids remain the cornerstone of treatment for symptomatic patients with pulmonary infiltrates and abnormal pulmonary function tests, with typical starting doses ranging from 20 to 40 mg/day followed by a slow taper over 6–18 months based on clinical and radiographic response. However, prolonged glucocorticoid therapy is associated with significant toxicity, and many patients require additional immunosuppressive agents for disease control or steroid-sparing purposes. Antimetabolites such as methotrexate, azathioprine, mycophenolate mofetil, and leflunomide are commonly used second-line therapies. For refractory disease, particularly in those with metabolically active lesions on FDG-PET, anti-tumor necrosis factor (TNF) agents like infliximab may be effective but carry risks of serious adverse effects. In select cases, newer strategies—including RCI, rituximab, JAKi or investigational regimens—are being explored. Management must also account for non-inflammatory complications such as sarcoidosis-associated pulmonary hypertension and bronchiectasis, which can mimic disease progression and require distinct therapeutic approaches. Given the heterogeneity of sarcoidosis and lack of robust clinical trial data, a stepwise and individualized approach to immunosuppression remains essential in optimizing outcomes while minimizing treatment-related harm. Full article
(This article belongs to the Special Issue Advanced Diagnostic and Therapeutic Strategies for Sarcoidosis)
Show Figures

Figure 1

36 pages, 2093 KB  
Review
Serum Sickness-Like Reaction: A Narrative Review of Epidemiology, Immunopathogenesis, Diagnostic Challenges, and Therapeutic Approaches
by Christodoulos Chatzigrigoriadis, Emmanouil Koufopoulos, Prodromos Avramidis, Ioannis Erginousakis, Vasiliki Karakoida, Theofanis Papadopoulos, Despoina Sperdouli, Myrsini-Eirini Tachliabouri, Kyriakos Vilanakis, Dimitrios Zampounidis, Vasiliki Michou, Panagiotis Eskitzis, Panagis Galiatsatos, Lazaros Lavasidis and Doxakis Anestakis
Clin. Pract. 2025, 15(10), 178; https://doi.org/10.3390/clinpract15100178 - 26 Sep 2025
Viewed by 612
Abstract
Serum sickness-like reaction (SSLR) is a rare immune-mediated condition that typically affects the skin and joints after exposure to certain drugs, infections, or vaccines. Although it shares clinical similarities with serum sickness (SS), SSLR differs in its underlying mechanisms, histopathology, and causes. Despite [...] Read more.
Serum sickness-like reaction (SSLR) is a rare immune-mediated condition that typically affects the skin and joints after exposure to certain drugs, infections, or vaccines. Although it shares clinical similarities with serum sickness (SS), SSLR differs in its underlying mechanisms, histopathology, and causes. Despite its generally benign and self-limiting nature, SSLR is frequently misdiagnosed and may lead to unnecessary hospitalization. This narrative review summarizes current knowledge on epidemiology, pathophysiology, clinical features, diagnosis, treatment, and long-term considerations related to SSLR. The condition is most often associated with antibiotics, monoclonal antibodies, and vaccines, particularly in pediatric populations. Its pathogenesis remains incompletely understood, but proposed mechanisms include immune complex formation, altered drug metabolism, lymphocyte toxicity, and the development of anti-drug antibodies. Diagnosis is primarily clinical, although novel diagnostic tools are emerging. Management involves discontinuation of the offending agent and supportive care, such as antihistamines or nonsteroidal anti-inflammatory drugs (NSAIDs) in mild cases, and corticosteroids in more severe cases. Long-term management, especially in cases requiring potential re-exposure to the causative agent, remains challenging. Skin testing and graded oral challenges appear promising within a structured clinical framework. Increased awareness of SSLR is essential for timely recognition and appropriate care, and further research is needed to elucidate its mechanisms and inform evidence-based management strategies. Full article
Show Figures

Figure 1

20 pages, 1150 KB  
Review
Uraemic Cardiomyopathy: A Nephrology-Centric Review of Pathophysiology, Clinical Features, and Emerging Management Strategies
by Mahmoud Elshehawy, Alaa Amr Abdelgawad, Elamin Mohammed, Mirza Yasar Baig, Hana Morrissey and Patrick Anthony Ball
J. CardioRenal Med. 2025, 1(1), 2; https://doi.org/10.3390/jcrm1010002 - 25 Sep 2025
Viewed by 318
Abstract
Background: Uraemic cardiomyopathy (UCM), the cardiac manifestation of chronic kidney disease, represents a significant clinical challenge that is often underdiagnosed despite being one of the strongest predictors of mortality in the chronic kidney disease (CKD) population. It develops through pathophysiological mechanisms unique to [...] Read more.
Background: Uraemic cardiomyopathy (UCM), the cardiac manifestation of chronic kidney disease, represents a significant clinical challenge that is often underdiagnosed despite being one of the strongest predictors of mortality in the chronic kidney disease (CKD) population. It develops through pathophysiological mechanisms unique to the uraemic state—left ventricular hypertrophy, myocardial fibrosis, and diastolic dysfunction—that often progress silently, sometimes even without traditional cardiovascular risk factors. Purpose: This review synthesises nephrology-centric mechanisms with clinical phenotypes and contemporary imaging (including CMR T1/T2 mapping and ECV), and proposes a CKD-stage–tailored diagnostic–therapeutic framework. It offers a distinct perspective by integrating the complex pathophysiology of UCM with practical diagnostic approaches and evolving management strategies, differentiating it from prior cardiology-focused overviews. Methods: A comprehensive literature search was conducted across Ovid MEDLINE, Embase, PubMed, Google Scholar, BMJ Best Practice, and UpToDate for studies published up to March 2025. Key findings were extracted from the final evidence set and manually verified for relevance. This review introduces a patho-mechanical cascade model of uraemic cardiomyopathy, integrating toxin-driven, metabolic, and haemodynamic axes. Nephrology-led screening protocols are proposed, leveraging proteomics and strain echo, and advocate mineralocorticoid receptor antagonists with sodium–glucose co-transporter-2 (SGLT2) inhibitor initiation at CKD Stage 3a. Cardiorenal clinics are essential for improved outcomes. Key Insights: UCM develops from a multifactorial process. This involves neurohormonal activation, oxidative stress, chronic inflammation, and exposure to toxins such as indoxyl sulfate and p-cresyl sulfate, arising from uraemia. Diagnosis is challenging, masked by overlapping features of fluid overload and anaemia. SGLT2 inhibitors, non-steroidal mineralocorticoid antagonists, and renin–angiotensin–aldosterone system modulation offer promising interventions. The effect of the dialysis modality, its timing, and renal transplantation on cardiac remodelling also emerging from recent studies. Conclusions: UCM sits at the intersection of two failing organ systems. Managing it effectively requires a paradigm shift to incorporate pharmacological and early diagnostic interventions and the integration of cardiology and nephrology care, and the timely implementation of interventions. Full article
Show Figures

Figure 1

Back to TopTop