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Search Results (3,479)

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30 pages, 1135 KB  
Review
Current Challenges and Approaches to the Development of Novel Drug Products for Otic Administration: A Narrative Review
by Elena O. Bakhrushina, Natalia N. Mikhailova, Anastasia N. Golub, Ksenia V. Eremeeva, Anna-Daniela Koynova, Anna A. Popova, Andrey B. Goryachev, Olga I. Stepanova, Ivan I. Krasnyuk and Ivan I. Krasnyuk
Sci. Pharm. 2026, 94(3), 55; https://doi.org/10.3390/scipharm94030055 (registering DOI) - 5 Jul 2026
Abstract
Acute otitis media is an inflammatory disease affecting all compartments of the middle ear, characterized by localized pain, fever, hearing impairment, and, occasionally, purulent exudate. It represents a significant clinical concern in both pediatric and adult populations, with approximately 709 million cases reported [...] Read more.
Acute otitis media is an inflammatory disease affecting all compartments of the middle ear, characterized by localized pain, fever, hearing impairment, and, occasionally, purulent exudate. It represents a significant clinical concern in both pediatric and adult populations, with approximately 709 million cases reported annually worldwide, 51% of which occur in children. However, currently available topical otic formulations are limited by their inability to achieve predictable therapeutic concentrations at the site of inflammation, resulting in reduced efficacy. In addition, the selection of appropriate active pharmaceutical ingredients (APIs) for drug products remains challenging; as a result, existing therapies do not comprehensively address all stages of pathogenesis. This study aimed to analyze existing locally acting formulations for middle ear drug delivery, evaluate their advantages and limitations, and assess modern approaches to the development of novel drug delivery systems and API combinations. A critical review of 69 publications (2010–2026) was conducted, supplemented by a strengths and limitations analysis of dosage forms and an evaluation of APIs based on clinical data. The findings highlight a lack of targeted drug delivery systems, limited efficacy of existing API combinations against bacterial biofilms, and their risk of ototoxicity. Emerging innovative drug delivery approaches, including microemulsions, vesicular systems, stimuli-responsive systems, and hydrogels, have demonstrated promising results in preclinical studies; however, their efficacy and safety remain to be confirmed in clinical settings before their full therapeutic potential in otitis media treatment can be realized. Full article
23 pages, 1205 KB  
Article
Effect of Fish-Derived Lipids on Inflammation Status and Health-Related Quality of Life in Women with Endometriosis
by Angelika Bogusz, Kacper Szewczyk, Dariusz Włodarek and Magdalena Górnicka
Nutrients 2026, 18(13), 2184; https://doi.org/10.3390/nu18132184 (registering DOI) - 5 Jul 2026
Abstract
Background: Endometriosis is a chronic, estrogen-dependent inflammatory disorder associated with pain and immune dysregulation. Omega-3 (n-3) fatty acids and fish-derived bioactive lipids may modulate inflammation and metabolism. This study investigated whether adding fish-derived lipids (FDLs) to a Healthy Eating Plate [...] Read more.
Background: Endometriosis is a chronic, estrogen-dependent inflammatory disorder associated with pain and immune dysregulation. Omega-3 (n-3) fatty acids and fish-derived bioactive lipids may modulate inflammation and metabolism. This study investigated whether adding fish-derived lipids (FDLs) to a Healthy Eating Plate diet improves inflammatory markers, gut inflammation, pain, and quality of life in women with endometriosis. Methods: In this 12-week randomized controlled trial, 46 women with confirmed endometriosis were assigned to either a Healthy Eating Plate diet alone (control group, CG) or the same diet plus FDLs (intervention group, IG). Primary outcomes included serum cytokine concentrations (interleukin [IL]-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha [TNF-α]) and fecal calprotectin (CAL). Secondary outcomes included pain intensity measured using the visual analog scale (VAS) and health-related quality of life assessed with the Endometriosis Health Profile-30 (EHP-30). Results: IL-10 levels (pg/mL) increased in the IG (32.5 ± 51.5 to 265 ± 508; p = 0.024) with a significant adjusted effect (ANCOVA: 5.07 [95% CI: 1.32–19.48], p = 0.019). Other cytokines showed heterogeneous responses, and CAL levels remained unchanged. EHP-30 Pain scores improved within both groups (CG p = 0.016; IG p = 0.002) without significant between-group change or adjusted effects (all p > 0.05). VAS scores decreased within the IG (5.0 ± 2.1 to 4.3 ± 2.1; p = 0.011), although there were no between-group differences in change and ANCOVA (all p > 0.05). However, ≥1-point responder rates were higher in the IG vs. CG (73.9% vs. 34.8%): adjusted RR = 2.11 (95% CI: 1.16; 3.89; p = 0.014). Conclusions: Overall, FDL supplementation was associated with a selected regulatory immune signal, reflected mainly by the IL-10 response, while most inflammatory, pain-related, and quality-of-life outcomes did not show consistent significant between-group effects. The observed greater likelihood of pain reduction in the FDL-supplemented group of women with endometriosis, along with the IL-10 response, should be interpreted with caution and confirmed in larger studies with longer follow-up/intervention time, taking into account the potential mechanisms of biological response. Full article
(This article belongs to the Special Issue Dietary Products for Women’s Reproductive Health and Diseases)
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7 pages, 628 KB  
Case Report
A Case of Spinal Epidural Abscess and Paraplegia After Group A Streptococcal Pharyngitis
by Blake J. McKinley, Rob M. Seby, Robert C. Chase, Tatjana Gavrancic, Jeremy Collado and Libardo Rueda Prada
Infect. Dis. Rep. 2026, 18(4), 68; https://doi.org/10.3390/idr18040068 (registering DOI) - 4 Jul 2026
Abstract
Background: Spinal epidural abscesses (SEA) are rare, occurring 2.5–3 times per 10,000 hospital admissions. While streptococcus species comprise 7% of reported SEAs, Group A Streptococcus (GAS) has been described only once in the medical literature to our knowledge. Case presentation: We [...] Read more.
Background: Spinal epidural abscesses (SEA) are rare, occurring 2.5–3 times per 10,000 hospital admissions. While streptococcus species comprise 7% of reported SEAs, Group A Streptococcus (GAS) has been described only once in the medical literature to our knowledge. Case presentation: We present a case of GAS pharyngitis with subsequent paraplegia from a GAS SEA. A 33-year-old female presented to the emergency department (ED) and was initially diagnosed with GAS pharyngitis and a suspected strained lower back. Following treatment with amoxicillin, she returned with worsened back pain, radiculopathy, and leukocytosis, for which she was treated with cyclobenzaprine. On her third presentation, she had new bilateral lower extremity weakness with decreased sensation, bilateral ankle clonus, and hyperreflexia. MRI of the thoracic and lumbar spine revealed a multiloculated SEA at T5-T10 requiring laminectomy and abscess evacuation. Intraoperative cultures grew Streptococcus pyogenes. Despite surgery, medical management, and physical therapy, she remained paraplegic. Conclusions: To our knowledge, this is the first report of SEA preceded by GAS pharyngitis. This case exposes the critical association between a recent infection, progression of back pain, eventual neurologic symptoms, and inflammatory markers that should trigger concern for SEA and early evaluation with MRI. Full article
(This article belongs to the Section Bacterial Diseases)
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29 pages, 1434 KB  
Review
Evolving Landscape of Regenerative Therapies: Cell-Based and Cell-Free Approaches for Chronic Low Back Pain
by Courtney E. Bartlett, Pareeshe Bansal, Siddhant Bhattacharya, Abhi Dhote, Bruna B. Nicoletto, Joana R. N. Lemos and Rahul Mittal
J. Clin. Med. 2026, 15(13), 5235; https://doi.org/10.3390/jcm15135235 (registering DOI) - 4 Jul 2026
Abstract
Background: Chronic low back pain (CLBP) is the leading cause of years lived with disability globally, affecting over 600 million individuals. Intervertebral disc degeneration (IVDD) is a principal structural contributor, yet conventional treatments, including pharmacotherapy, physical therapy, and surgical intervention, do not reverse [...] Read more.
Background: Chronic low back pain (CLBP) is the leading cause of years lived with disability globally, affecting over 600 million individuals. Intervertebral disc degeneration (IVDD) is a principal structural contributor, yet conventional treatments, including pharmacotherapy, physical therapy, and surgical intervention, do not reverse the underlying degenerative pathology. Regenerative medicine has introduced a spectrum of biological therapies for IVDD, including cell-based mesenchymal stromal cell (MSC) therapy, platelet-derived products such as platelet-rich plasma (PRP) and platelet lysate, extracellular vesicle-based approaches using MSC-derived extracellular vesicles (EVs), and secretome-based therapies using MSC-derived secretomes. However, these approaches have largely been studied in isolation, without a unified framework to compare their respective advantages and limitations in CLBP secondary to IVDD. Accordingly, this narrative review aims to provide an integrated and comparative evaluation of these regenerative strategies within a single translational and clinical context. Methods: For this narrative review, PubMed, Scopus, and Web of Science were searched from January 2000 to January 2026 using terms combining regenerative modalities with intervertebral disc degeneration, and chronic low back pain. Randomized controlled trials (RCTs), prospective cohort studies, systematic reviews, and preclinical studies with translational relevance were included. Results: Intradiscal MSC therapy has demonstrated safety across multiple phase I–III trials, but two recent landmark RCTs (RESPINE and the Mesoblast phase III trial) failed to meet primary efficacy endpoints, highlighting the gap between preclinical promise and clinical outcomes. PRP has the largest clinical evidence base, with level II evidence supporting short- to medium-term pain relief for discogenic pain, although standardization remains a critical barrier. Platelet lysate, MSC-derived EVs, and MSC-derived secretomes show compelling preclinical data, including extracellular matrix restoration, anti-inflammatory modulation, and attenuation of nucleus pulposus cell apoptosis, but remain at early translational stages for spinal applications, with no completed RCTs. The hostile disc microenvironment (avascular, hypoxic, acidic, and nutrient-poor) poses unique challenges for all regenerative modalities, differing fundamentally from other musculoskeletal applications. Conclusions: The studies included in this narrative review suggest that no single regenerative modality has yet shown consistent and unequivocal efficacy for CLBP secondary to IVDD across clinical trials. Cell-free approaches offer manufacturing, scalability, and safety advantages over cell-based therapies, but lack clinical validation. Future progress requires standardized preparation protocols, disc-specific delivery systems, patient phenotyping strategies, and rigorously designed comparative clinical trials. This narrative review provides a framework for researchers and clinicians to evaluate these therapies in context rather than isolation. Full article
(This article belongs to the Section Clinical Rehabilitation)
23 pages, 1809 KB  
Review
From Endometriosis to Lipedema: Toward a Neuroimmune Framework for Pain Amplification in Hormone-Sensitive Disorders
by Diogo Pinto da Costa Viana, Thiago Bracks Oliveira, Adriana Luckow Invitti and Eduardo Schor
Biomedicines 2026, 14(7), 1510; https://doi.org/10.3390/biomedicines14071510 - 3 Jul 2026
Viewed by 137
Abstract
Background: Endometriosis and lipedema are chronic female-predominant disorders characterized by persistent pain that is frequently disproportionate to anatomical lesion burden. Although traditionally interpreted within distinct lesion-centered frameworks, both conditions exhibit striking clinical and epidemiological parallels, including hormonally modulated symptom dynamics, overlap with [...] Read more.
Background: Endometriosis and lipedema are chronic female-predominant disorders characterized by persistent pain that is frequently disproportionate to anatomical lesion burden. Although traditionally interpreted within distinct lesion-centered frameworks, both conditions exhibit striking clinical and epidemiological parallels, including hormonally modulated symptom dynamics, overlap with central pain syndromes, weak correlation between structural disease severity and pain intensity, and symptom clustering during reproductive transitions such as puberty, pregnancy, and menopause. Methods: This study aims to synthesize clinical, molecular, neuroimmune, and endocrine evidence on the interrelationship between endometriosis and lipedema, and to propose a hypothesis-generating neuroimmune framework linking both conditions. This integrative narrative review conducted a non-systematic literature search in PubMed/MEDLINE, Scopus, and Web of Science, focusing on mechanisms related to chronic pain, mast cell biology, TRPV1 signaling, CGRP-mediated neurogenic inflammation, intracrine steroidogenesis, and peripheral and central sensitization. Results: The review identifies convergent biological characteristics between the two diseases, including mast cell activation, macrophage polarization, endothelial dysfunction, fibrosis, angiogenesis, intracrine estrogen metabolism, and persistent inflammatory signaling. In endometriosis, direct evidence demonstrates increased sensory innervation, nerve growth factor expression, TRPV1 sensitization, CGRP-positive fibers, and mast cell-nerve interactions. In lipedema, convergent upstream mechanisms, including mast cell infiltration, elevated histamine levels, adipose tissue inflammation, and local estrogen activation, support the plausibility of a functionally analogous neuroimmune organization, despite incomplete direct neural characterization. In this context, the mast cell-TRPV1-CGRP axis is proposed as a biologically plausible framework, directly supported in endometriosis and currently hypothetical in lipedema, connecting peripheral sensitization, neurogenic inflammation, hormonal chronodependence, and central nociceptive amplification. The model further conceptualizes pain crises as transient events of instability within a sensitized neuroimmune network and proposes mechanistic phenotypes that integrate gastrointestinal, inflammatory, central, and hormonal triggers. Conclusion: Endometriosis and lipedema may represent topographically distinct manifestations of a shared neuroimmune process operating within hormone-sensitive tissues. Although the evidentiary basis remains asymmetric, with stronger mechanistic support in endometriosis than in lipedema, this framework provides a biologically plausible and experimentally testable model integrating endocrine, immune, neural, and vascular contributors to chronic pain amplification. This perspective supports coordinated translational investigation across reproductive biology, endocrinology, and pain medicine and may contribute to future mechanism-based stratification and therapeutic development. This work is hypothesis-generating and is not intended to establish causality or to provide clinical recommendations; all proposed mechanistic and therapeutic inferences require prospective experimental validation. Full article
17 pages, 2495 KB  
Article
Metabolic and Laboratory Biomarkers in Early-Onset Versus Late-Onset Colorectal Cancer: A Case–Control Study
by Mohamed H. Eldesouki, Ahmed E. Salem, Youssef Hafez, Ezz ElDien A. Ibrahim, Mohammed Y Youssef, Fatima Khan, Mohammed Alomari, Sherif E. ElHananfi and Aasma Shaukat
Cancers 2026, 18(13), 2152; https://doi.org/10.3390/cancers18132152 - 3 Jul 2026
Viewed by 210
Abstract
Background: The incidence of early-onset colorectal cancer (EOCRC) is rising, yet the relative contribution of metabolic, inflammatory, and laboratory abnormalities remains incompletely defined. Objectives: We compared these associations between EOCRC and late-onset colorectal cancer (LOCRC) while addressing the possibility that some laboratory abnormalities [...] Read more.
Background: The incidence of early-onset colorectal cancer (EOCRC) is rising, yet the relative contribution of metabolic, inflammatory, and laboratory abnormalities remains incompletely defined. Objectives: We compared these associations between EOCRC and late-onset colorectal cancer (LOCRC) while addressing the possibility that some laboratory abnormalities may reflect occult cancer rather than antecedent risk. Methods: We conducted a matched case–control study using the TriNetX US Network. Adults diagnosed with CRC between 2010 and 2023 were identified as EOCRC (18–49 years) or LOCRC (50–75 years). Patients with prior malignancy, inflammatory bowel disease, hereditary or familial CRC risk, or prior colectomy were excluded. Three separate analyses were performed. First, a direct EOCRC-versus-LOCRC comparison evaluated gastrointestinal symptoms during the 6 months preceding diagnosis. Second, EOCRC and LOCRC were each compared with their respective matched cancer-free controls to assess clinical, metabolic, and laboratory features during the 24 months preceding diagnosis. When multiple laboratory values were available, the most recent value preceding the index date was used. Conditional logistic regression estimated adjusted odds ratios with 95% confidence intervals, with Bonferroni correction applied for multiple comparisons. Results: The direct matched EOCRC-versus-LOCRC comparison included 7752 patients with CRC, comprising 2584 with EOCRC and 5168 with LOCRC. EOCRC more frequently presented with rectal bleeding, abdominal pain, diarrhea, iron-deficiency anemia, and weight loss. Rectal tumors were more common in EOCRC, whereas proximal tumors were more common in LOCRC. In separate control-based analyses, 3217 patients with EOCRC and 12,112 patients with LOCRC were compared with 6434 and 24,336 matched cancer-free controls, respectively. The strongest independent features associated with EOCRC were severe obesity (aOR 2.61), microcytosis (aOR 2.29), low ferritin (aOR 2.11), and elevated C-reactive protein (aOR 1.87). Similar but generally attenuated associations were observed in LOCRC. In adjusted EOCRC-versus-LOCRC analyses, obesity (aOR 1.38), metabolic syndrome (aOR 1.41), and MASH (aOR 1.22) remained more closely associated with EOCRC. Conclusions: EOCRC is associated with a distinct clinical–metabolic phenotype, with more pronounced metabolic, inflammatory, and hematologic abnormalities than LOCRC. These findings should be interpreted as hypothesis-generating prediagnostic associations, not as validated predictors or causal risk factors. Full article
(This article belongs to the Section Cancer Biomarkers)
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22 pages, 4766 KB  
Article
Integrated Multi-Sensor Assessment System for Objective Muscle Recovery Monitoring: Application of Isokinetic Dynamometry, Infrared Thermometry, and Multi-Biomarker ELISA in Exercise-Induced Muscle Damage Surveillance
by Soungyob Rhi and Bonggeun Sin
Sensors 2026, 26(13), 4215; https://doi.org/10.3390/s26134215 - 3 Jul 2026
Viewed by 152
Abstract
Purpose: This study aimed to develop and validate a comprehensive multi-sensor integrated platform for objective assessment of skeletal muscle recovery kinetics following exercise-induced muscle damage (EIMD), combining biomechanical, thermal, and biochemical monitoring modalities. Methods: Forty elite male athletes were randomized to microwave diathermy [...] Read more.
Purpose: This study aimed to develop and validate a comprehensive multi-sensor integrated platform for objective assessment of skeletal muscle recovery kinetics following exercise-induced muscle damage (EIMD), combining biomechanical, thermal, and biochemical monitoring modalities. Methods: Forty elite male athletes were randomized to microwave diathermy (MWD, n = 20, 2.45 GHz, 160 W, 45 min/session) or control (n = 20) groups. Time-synchronized multi-sensor assessments at baseline, 24 h, 48 h, and 72 h post-EIMD included: biomechanical sensors (knee flexion range of motion via goniometry and isokinetic peak torque), thermal sensor (skin surface temperature via infrared thermometry), and biochemical sensor array (serum CK, IL-6, and CRP via high-sensitivity ELISA). Two-way repeated-measures ANOVA with Bonferroni correction examined group × time interactions across all sensor channels. Results: Pre-study validation confirmed high reliability across all sensor modalities. Cross-modality concordance analysis revealed significant correlations between biomechanical and biochemical recovery trajectories (isokinetic torque vs. IL-6: r = −0.73, p < 0.001; pain vs. IL-6: r = 0.68, p < 0.001). MWD intervention demonstrated accelerated recovery across all sensor channels: complete ROM recovery by 48 h (MWDG post-2 vs. baseline, p > 0.05; CG post-3 43% below baseline, p < 0.001), complete isokinetic torque restoration by 72 h (MWDG post-3 vs. baseline, p > 0.05; CG 44% below baseline, p < 0.001), and near-complete pain resolution (VAS 1.70 ± 2.50 mm, p < 0.05). Biomarker sensors demonstrated differential recovery kinetics: IL-6 normalized by 48 h (1.52 ± 0.14 pg/mL, p > 0.05 vs. baseline), CRP approached baseline by 72 h (0.73 ± 0.24 mg/L, p > 0.05), while CK remained elevated at post-3 (169.70 ± 22.58 U/L, 30% above baseline, p < 0.001), indicating incomplete myofiber membrane integrity recovery despite resolution of systemic inflammatory markers. The control group exhibited persistent deficits across all sensor channels with no clinically meaningful recovery. Conclusions: This study validated an integrated multi-sensor platform for recovery assessment. Microwave diathermy demonstrated efficacy by 72 h with complete functional recovery and inflammatory normalization (though CK remained elevated). Cross-modality concordance (r = −0.73 to 0.68) confirmed superior assessment compared to single-modality approaches. This laboratory-based methodology provides a framework for future portable sensor systems in athletic surveillance. Full article
(This article belongs to the Collection Sensor Technology for Sports Science)
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6 pages, 1406 KB  
Case Report
Fluoroscopy-Guided Injection of Autologous Mechanically Filtered Adipose Tissue for Chronic Sacroiliac Joint Pain: A Case Report
by Bruno De Meo, Alfonso Maria Forte, Elisa Palombo, Hassan Zmerly and Luigi Di Lorenzo
Surgeries 2026, 7(3), 80; https://doi.org/10.3390/surgeries7030080 - 2 Jul 2026
Viewed by 101
Abstract
Introduction: Chronic sacroiliac joint (SIJ) pain is a frequent cause of low-back pain and remains challenging to diagnose and treat due to complex anatomy, overlapping clinical features, and limited long-term efficacy of conventional therapies. Case Presentation: We report the case of a 74-year-old [...] Read more.
Introduction: Chronic sacroiliac joint (SIJ) pain is a frequent cause of low-back pain and remains challenging to diagnose and treat due to complex anatomy, overlapping clinical features, and limited long-term efficacy of conventional therapies. Case Presentation: We report the case of a 74-year-old woman with chronic right-sided sacroiliitis associated with spondyloarthritis, presenting with persistent gluteal pain refractory to nonsteroidal anti-inflammatory drugs, physiotherapy, and steroid injections. The patient underwent a dual imaging-guided intra-articular injection, consisting of pre-procedural ultrasound assessment and fluoroscopy-guided needle placement to confirm intra-articular access prior to injection. Autologous adipose tissue purified through mechanical filtration, without enzymatic manipulation, was administered. Pain intensity decreased from a visual analog scale (VAS) score of 8/10 at baseline to 2/10 at three months, with sustained improvement up to 12 months, functional recovery, and discontinuation of analgesic therapy, without procedure-related complications. Conclusions: This case suggests that dual imaging-guided intra-articular injection of mechanically filtered autologous adipose tissue may be feasible in selected patients with refractory SIJ pain. No causal inference can be drawn from a single case, and further studies are required to evaluate safety and clinical effectiveness. Full article
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25 pages, 3191 KB  
Article
Antinociceptive Activity of Petiveria alliacea L. Extract via GABAergic and Serotonergic Pathways in Diabetic Neuropathy Model
by Kelly del C. Cruz-Salomón, Alfredo Briones-Aranda, Abumalé Cruz-Salomón, Nancy Ruiz-Lau, Mariano Martínez-Vázquez, Joaquín A. Montes-Molina, Gerardo Leyva-Padrón, Josue V. Espinosa-Juárez and Rosa I. Cruz-Rodríguez
Sci. Pharm. 2026, 94(3), 54; https://doi.org/10.3390/scipharm94030054 - 2 Jul 2026
Viewed by 242
Abstract
Petiveria alliacea L. (commonly known as “anamu,” “guiné,” “hierba de zorro,” and “tipi”) has been widely used in Mesoamerican traditional medicine to treat pain and inflammation. However, scientific evidence supporting its efficacy in diabetic neuropathy remains limited. This study evaluated the antinociceptive potential [...] Read more.
Petiveria alliacea L. (commonly known as “anamu,” “guiné,” “hierba de zorro,” and “tipi”) has been widely used in Mesoamerican traditional medicine to treat pain and inflammation. However, scientific evidence supporting its efficacy in diabetic neuropathy remains limited. This study evaluated the antinociceptive potential of a methanolic leaf extract of P. alliacea in a murine model of alloxan-induced diabetic neuropathy and investigated its possible mechanisms of action. Diabetic CD-1 mice were evaluated for mechanical allodynia and hyperalgesia using the Von Frey test and for tonic pain using the formalin test. Pharmacological antagonists were administered to assess the involvement of opioid, nitric oxide, serotonergic, and GABAergic pathways. Phytochemical profiling was performed by LC-ESI-MS/MS, and potential pharmacological and pharmacokinetic properties of the identified metabolites were predicted using in silico tools (PASS online, SwissTargetPrediction, SwissADME, and pkCSM). The methanolic extract significantly reduced mechanical allodynia and hyperalgesia in diabetic mice and attenuated nociceptive responses in both phases of the formalin test, showing an effect comparable to gabapentin. Antinociceptive activity was not altered by naloxone or L-NAME but was significantly attenuated by methiothepin and bicuculline, suggesting that serotonergic and GABAergic pathways contribute, at least in part, to the observed antinociceptive effects. LC-ESI-MS/MS analysis identified 38 metabolites, including flavonoids, alkaloids, and terpenes, with in silico predictions supporting their potential analgesic and anti-inflammatory activities. The methanolic leaf extract of P. alliacea exhibits significant antinociceptive activity in diabetic neuropathy, partially likely to involve serotonergic and GABAergic mechanisms, supporting its ethnomedicinal use and its potential as a source of novel analgesic agents. Full article
(This article belongs to the Topic Natural Products and Drug Discovery—2nd Edition)
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12 pages, 4959 KB  
Case Report
Rescue Vedolizumab Therapy for a Rare Case of Complicated Severe Ulcerative Colitis: A Case Report and Literature Review
by Shih-Tsung Fu, Kai-Po Chang, Wei-Jhe Hong, Jen-Wei Chou and Yi-Hua Wu
J. Clin. Med. 2026, 15(13), 5166; https://doi.org/10.3390/jcm15135166 - 2 Jul 2026
Viewed by 118
Abstract
Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with extraintestinal manifestations, including primary sclerosing cholangitis (PSC). Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that rarely coexists with UC or PSC. The concurrent occurrence of UC, PSC, and SLE [...] Read more.
Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with extraintestinal manifestations, including primary sclerosing cholangitis (PSC). Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that rarely coexists with UC or PSC. The concurrent occurrence of UC, PSC, and SLE in a single individual represents a unique diagnostic and therapeutic challenge. Vedolizumab, a gut-selective biologic agent, is effective for managing UC; however, its utility in patients presenting with this triad of conditions has not yet been explored. Case summary: A 32-year-old man presented with a 10-year history of recurrent upper abdominal pain, frequently accompanied by high-grade fever, along with recent onset of jaundice, diarrhea, hematochezia, and chronic rashes. Diagnostic evaluation confirmed PSC, SLE, and severe UC. During hospitalization, the patient also developed bacteremia. Initial management of UC with mesalazine and immunosuppressants (azathioprine followed by cyclosporine) resulted in limited clinical improvement. Vedolizumab was subsequently initiated, resulting in marked clinical improvements and near-complete endoscopic remission of UC. PSC and SLE remained clinically stable with ongoing therapies; however, the patient is currently awaiting liver transplantation for PSC. Conclusions: This case highlights the potential utility of vedolizumab in the treatment of UC in patients with concurrent PSC and SLE. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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16 pages, 1245 KB  
Systematic Review
Salivary Oxidative Stress Biomarkers in Temporomandibular Disorders: A Systematic Review and Meta-Analysis
by Luis Chauca Bajaña, Tatiana Cruz Moreno, Diego Quiguango Farias, Sandra Vélez Cevallos, Eliana Pazmiño Troncoso, Alisson Juiña Jaime, Mauricio Rosales Pavón and Byron Velásquez Ron
J. Pers. Med. 2026, 16(7), 357; https://doi.org/10.3390/jpm16070357 - 30 Jun 2026
Viewed by 114
Abstract
Background: Temporomandibular disorders (TMD) are multifactorial musculoskeletal conditions frequently associated with chronic pain, inflammation, and functional impairment. Increasing evidence suggests that oxidative stress may contribute to the pathophysiology of TMD, and salivary biomarkers have emerged as a promising non-invasive approach for evaluating these [...] Read more.
Background: Temporomandibular disorders (TMD) are multifactorial musculoskeletal conditions frequently associated with chronic pain, inflammation, and functional impairment. Increasing evidence suggests that oxidative stress may contribute to the pathophysiology of TMD, and salivary biomarkers have emerged as a promising non-invasive approach for evaluating these biological alterations. Objective: This systematic review and meta-analysis aimed to systematically evaluate and quantitatively synthesize the available evidence regarding salivary oxidative stress biomarkers in patients with temporomandibular disorders compared with healthy controls. Materials and Methods: A systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines and prospectively registered in PROSPERO. Electronic searches were performed in PubMed/MEDLINE, Embase, Scopus, and Web of Science databases. Observational studies and clinical trials evaluating salivary oxidative stress biomarkers in patients with TMD were included. The primary biomarkers assessed were malondialdehyde (MDA), total antioxidant capacity (TAC), and catalase activity (CAT). Data extraction and risk of bias assessment were independently performed by two reviewers using the Newcastle–Ottawa Scale and RoB 2 tool when applicable. Random-effects meta-analyses were conducted using weighted or standardized mean differences with 95% confidence intervals. Included studies demonstrated substantial methodological variability regarding TMD diagnostic criteria, saliva collection protocols, biomarker assays, and sampling conditions. Results: Pooled analyses showed significantly elevated salivary malondialdehyde levels in patients with TMD compared with healthy controls, suggesting increased lipid peroxidation and oxidative stress activity. In contrast, total antioxidant capacity and catalase activity demonstrated inconsistent and non-significant findings across studies. Considerable heterogeneity was identified among studies, limiting the comparability and interpretability of pooled estimates. Salivary oxidative stress biomarkers, particularly malondialdehyde, appear to be associated with temporomandibular disorders and may reflect underlying oxidative and inflammatory mechanisms. Conclusions: However, substantial methodological heterogeneity and lack of standardized protocols currently limit their clinical applicability. Future well-designed longitudinal studies using harmonized diagnostic and analytical methodologies are required to clarify their translational value in TMD assessment. Full article
(This article belongs to the Section Disease Biomarkers)
37 pages, 4117 KB  
Article
A Comprehensive Chemical–Biological Investigation of the Moderately Toxic Plant Prospero autumnale: Insights into Its Bioactive Potential Using In Vitro and In Vivo Models
by Maroua Korichi, Ouanissa Smara, Lilya Harchaoui, Gilda D’Urso, Latifa Khattabi, Agostino Casapullo, Gianluigi Lauro, Maria Giovanna Chini, Giuseppe Bifulco, Alessio Cimmino, Hocine Dendougui, Wafa Zahnit, Marco Masi and Mahdi Belguidoum
Toxins 2026, 18(7), 285; https://doi.org/10.3390/toxins18070285 - 30 Jun 2026
Viewed by 138
Abstract
Prospero autumnale L. is a Mediterranean medicinal plant traditionally employed for inflammatory and neurological disorders. Nonetheless, its safety profile, toxicity, and application for treating inflammation and pain are yet to be comprehensively established. This investigation aimed to assess the bioactivity and toxicity of [...] Read more.
Prospero autumnale L. is a Mediterranean medicinal plant traditionally employed for inflammatory and neurological disorders. Nonetheless, its safety profile, toxicity, and application for treating inflammation and pain are yet to be comprehensively established. This investigation aimed to assess the bioactivity and toxicity of extracts derived from its aerial (AgP) and underground (UgP) parts. The phytochemical constituents of various P. autumnale extracts were analyzed using LC-MS/MS, and their phenolic content was quantified. The biological activities were evaluated through in vitro assays—including antioxidant, anti-inflammatory, acetylcholinesterase-inhibitory, and photoprotection assessments—and in vivo experiments, including evaluations of acute oral toxicity, anti-inflammatory, and analgesic effects. UgP extracts demonstrated significant antioxidant activity, with the methanolic extract exhibiting the highest reducing and superoxide scavenging capacities. Dichloromethane and ethyl acetate extracts performed exceptionally well in ABTS and DPPH assays. The aqueous extract from AgP exhibited noteworthy anti-inflammatory and analgesic effects, surpassing diclofenac in vitro and demonstrating efficacy in vivo. It also showed considerable acetylcholinesterase inhibition, while the ethyl acetate extract displayed high photoprotective potential. The acute toxicity was moderate (LD50: 300–400 mg/kg), indicating dose-dependent risks. LC-MS/MS analysis revealed diverse phenolics potentially contributing to both therapeutic and adverse effects. This research enhances the medicinal prospects of P. autumnale, provides new perspectives on plant utilization, and suggests its potential as a natural anti-inflammatory agent. However, due to moderate toxicity and dose-dependent effects, cautious application is advised. These findings underscore the importance of toxicological evaluation alongside bioactivity screening in ethnopharmacology to ensure safety. Full article
(This article belongs to the Special Issue Toxicity of Plant Natural Products and Their Applications)
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19 pages, 604 KB  
Article
Presentation and Clinical Outcomes of Inflammatory Bowel Disease in Children and Adolescents at a Tertiary Care Center in Lebanon
by Tracy Daoud, Sarah Khafaja, Rima Hanna-Wakim and Nadine Yazbeck
J. Clin. Med. 2026, 15(13), 5105; https://doi.org/10.3390/jcm15135105 - 30 Jun 2026
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Abstract
Background: Pediatric-onset inflammatory bowel disease (IBD) is a chronic relapsing condition leading to substantial morbidity and variable disease course. Early recognition of factors associated with suboptimal outcomes may improve risk stratification and therapeutic strategy. This retrospective cohort study intended to analyze the [...] Read more.
Background: Pediatric-onset inflammatory bowel disease (IBD) is a chronic relapsing condition leading to substantial morbidity and variable disease course. Early recognition of factors associated with suboptimal outcomes may improve risk stratification and therapeutic strategy. This retrospective cohort study intended to analyze the association between initial presentation characteristics and early disease course in pediatric-onset IBD. Methods: Included were pediatric patients diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC) followed at the American University of Beirut Medical Center between 2013 and 2023. Demographic, anthropometric, laboratory, endoscopic, radiologic, and clinical data were gathered from medical records. Validated pediatric activity indices were used to assess severity, and early outcomes covered mainly the first remission. Results: Eighty-eight patients were evaluated for baseline characteristics, and eighty-one patients were analyzed for treatment outcomes. Among 88 subjects, 62.5% had CD and 37.5% had UC, with a mean age at diagnosis of 11.29 (±4.60) years. The most encountered presenting symptoms were abdominal pain, diarrhea, and hematochezia, with 44.9% of subjects having malnutrition. Clinical remission after initial treatment was obtained in 60.2% of subjects. A past medical history of autoimmune or inflammatory disease was linked to persistent symptoms, whereas initial use of corticosteroids was associated with early clinical remission. Conclusions: Pediatric IBD in our cohort was marked by extensive disease involvement, high inflammatory burden, nutritional impairment, and frequent flare or treatment escalation. Corticosteroid initiation at diagnosis was associated with early clinical remission in this retrospective cohort. Nevertheless, this association should be interpreted cautiously, as the retrospective design and potential confounding by indication limit any inference regarding causality or treatment superiority. The high rate of subsequent flare underscores the need for early risk stratification and individualized multidisciplinary care to improve long-term outcomes. Full article
(This article belongs to the Special Issue New Updates in Pediatric Gastroenterology)
16 pages, 1509 KB  
Article
Short-Term Clinical Outcomes and Systemic Inflammatory Biomarker Responses Following Platelet-Rich Plasma Injection in Knee Osteoarthritis
by Viorela Mihaela Ciortea, Alina Deniza Ciubean, Titus Vari, Irina Motoașcă, Oana Valentina Harșa, Theodor Popa, Mădălina-Gabriela Iliescu, Liliana-Elena Stanciu, Florina-Ligia Popa, Tudor-Ștefan Ciortea, Liviuta Budișan, Cosmina Ioana Bondor and Laszlo Irsay
Life 2026, 16(7), 1097; https://doi.org/10.3390/life16071097 - 30 Jun 2026
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Abstract
Background: Knee osteoarthritis (KOA) is a degenerative joint disorder characterized by chronic pain, functional limitation, and low-grade inflammation. While platelet-rich plasma (PRP) has gained traction as a biologic therapy, the relationship between short-term clinical outcomes and systemic inflammatory biomarker dynamics remains poorly understood [...] Read more.
Background: Knee osteoarthritis (KOA) is a degenerative joint disorder characterized by chronic pain, functional limitation, and low-grade inflammation. While platelet-rich plasma (PRP) has gained traction as a biologic therapy, the relationship between short-term clinical outcomes and systemic inflammatory biomarker dynamics remains poorly understood in routine clinical settings. Methods: This prospective observational study evaluated 40 patients with grade 2–3 KOA receiving a single ultrasound-guided intra-articular PRP injection. Clinical outcomes via the Visual Analog Scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Short Form-36 (SF-36), alongside serum inflammatory markers (IL-1β, IL-8, IL-18, TNF-α, erythrocyte sedimentation rate, and C-reactive protein), were assessed at baseline and 4 weeks post-injection using paired tests and multivariable regression. Results: At 4 weeks, clinical scores improved significantly (all p < 0.001). Circulating IL-8 and TNF-α levels decreased significantly (p = 0.009 and p = 0.014, respectively), whereas IL-1β and IL-18 variations were non-significant. Baseline cytokines did not predict clinical outcomes, but a significant association emerged between ΔIL-18 and ΔWOMAC (p = 0.032). Conclusions: A single intra-articular PRP injection was associated with short-term clinical improvements and selected reductions in circulating IL-8 and TNF-α, although the clinical significance of these biomarker changes remains uncertain. Given the observational design and short follow-up, these preliminary findings require confirmation in larger controlled trials. Full article
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25 pages, 1149 KB  
Review
Artificial Intelligence in Inherited Epidermolysis Bullosa: Current Evidence, Challenges, and Future Directions
by Ashjan Alheggi
Diagnostics 2026, 16(13), 2022; https://doi.org/10.3390/diagnostics16132022 - 29 Jun 2026
Viewed by 228
Abstract
Epidermolysis bullosa (EB) comprises a group of rare inherited genodermatoses characterized by fragility and blistering of the skin and mucous membranes, chronic wounding, and significant morbidity including increased risk of squamous cell carcinoma in severe subtypes. Key unmet priorities include reducing diagnostic latency, [...] Read more.
Epidermolysis bullosa (EB) comprises a group of rare inherited genodermatoses characterized by fragility and blistering of the skin and mucous membranes, chronic wounding, and significant morbidity including increased risk of squamous cell carcinoma in severe subtypes. Key unmet priorities include reducing diagnostic latency, establishing objective wound monitoring, enabling early detection of malignant transformation within chronic ulcerations, and developing therapies that durably modify disease progression. Artificial intelligence (AI) encompassing machine learning (ML), and deep learning (DL) is increasingly integrated into EB research and clinical practice to address these unmet needs. This structured narrative review synthesises current evidence on AI applications in EB spanning genetic diagnostics, wound assessment, inflammatory endotyping, drug repurposing, and emerging therapeutic technologies, and integrates evidence from registered clinical trials. In genomics, DL-based splicing prediction models and variant prioritisation frameworks accelerate pathogenic variant detection and reduce diagnostic latency. In wound care, convolutional neural networks-based platforms enable automated lesion segmentation and remote monitoring, while multimodal AI models predict healing trajectories and support stratification of wounds by chronicity. Computational transcriptomic analyses have identified candidate repurposing agents by reversing pathogenic gene expression signatures in EB tissue. Emerging convergence of AI with biosensors-integrated wound dressings and three-dimensional bioprinting of genetically corrected skin substitutes represents a transformative future direction. Translational barriers include limited EB-specific training datasets, algorithmic bias across diverse skin phototypes, the interpretability deficit of DL systems, and evolving regulatory frameworks for AI as a medical device. Expansion of internationally interoperable EB disease registries with standardised wound imaging protocols is identified as the single most impactful intervention to accelerate AI adoption. A minimum endpoint set for AI-assisted EB wound assessment, incorporating wound area trajectory, wound type classification, tissue composition, and paired patient-reported pain and itch scores, is proposed to standardise outcome reporting across future studies. Full article
(This article belongs to the Special Issue Artificial Intelligence in Dermatology)
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