Search Results (7,771)

This study aimed to evaluate the therapeutic effects of platelet-rich plasma (PRP) and Cervus and Cucumis polypeptide (CCP) injections in rats with post-traumatic osteoarthritis (OA). The model was established by transection of the anterior cruciate ligament, and the animals were subsequently treated with PRP and CCP. Articular cartilage degeneration was assessed through gross morphological observation, histopathological staining, and a standardized scoring system. Concurrently, pain-related behaviors, joint swelling, levels of inflammatory cytokines, and markers associated with extracellular matrix degradation were measured. The results demonstrated that, compared with the OA model group, PRP and CCP exhibited varying degrees of functional improvement, specifically, a reduction in pain-related behaviors and an alleviation of joint swelling. Furthermore, cartilage morphological damage was diminished, inflammatory marker levels decreased, and indicators of extracellular matrix degradation were attenuated. Histopathological examination of liver and kidney tissues revealed no apparent abnormalities. This study provides valuable experimental evidence for further treatment strategies for OA. Full article

Background: In zoster-associated pain (ZAP), earlier epidural steroid injection (ESI) has been associated with better outcomes, but optimal timing remains unclear, and prior studies have largely relied on pain reduction alone. Methods: In this multicenter retrospective cohort, 215 patients with ZAP who completed a three-session ESI course were classified into early (<30 days) and delayed (≥30–≤180 days) groups. The primary endpoint was complete remission at 12 weeks (≥50% visual analog scale [VAS] reduction, VAS ≤ 2, and sensory normalization); successful response (≥50% VAS reduction) served as the secondary endpoint. An ordered three-category framework and an exploratory generalized Youden index threshold analysis were applied. Results: Complete remission occurred in 82.1% versus 39.0% and successful response in 91.7% versus 67.8%. Each additional day of delay was associated with lower odds of complete remission (adjusted odds ratio [aOR], 0.957; p < 0.001) and higher odds of a worse outcome category (aOR, 1.030; p < 0.001). Exploratory candidate boundaries were 22 and 42 days. Conclusions: Earlier ESI initiation was associated with a higher likelihood of complete remission incorporating pain reduction, low residual pain intensity, and sensory normalization. These findings highlight the clinical relevance of treatment timing and recovery assessment beyond pain reduction alone in ZAP. Full article

Background/Objectives: Exploiting the metabolic properties of postbiotics is a novel strategy for managing metabolic disorders, including diabetes. Inactivated microorganisms, a major class of postbiotics, improve glycemic control in preclinical and clinical studies. Here, we examined whether heat-killed (HK) Mycobacterium aurum (M. aurum) exerts prophylactic or therapeutic anti-hyperglycemic effects in diabetic mice. Methods: Diabetes was induced in male BALB/c mice by streptozotocin (STZ; 150 mg/kg) injection. HK M. aurum (1 mg) was given orally (three prophylactic doses before STZ) or intradermally (six weekly therapeutic doses after STZ). We assessed glycemic parameters, serum C-peptide/insulin (ELISA), and tissue protein expression (Western blot). Results: Neither route altered body weight or glucose homeostasis in non-diabetic mice. In STZ-diabetic mice, oral prophylactic treatment significantly attenuated hyperglycemia (39–60% reduction weeks 5–8 post-STZ) and showed a trend toward improved serum C-peptide, but did not affect dysregulated expression of skeletal muscle (SM), hepatic, pancreatic and renal proteins involved in glucose transport (GLUT2, GLUT4, and SGLT2), glycolysis (α-LDH), mitochondrial uncoupling (UCP2 and UCP3), and antioxidant defense (CAT). Therapeutic intradermal administration significantly decreased blood glucose (~30% at week 5, ~40% at week 6) and modestly enhanced insulin secretion. Hepatic UCP2 and α-LDH and SM UCP3 protein levels were normalized toward non-diabetic levels, whereas hepatic GLUT2 and SM GLUT4 remained largely unchanged. These correlative findings suggest effects independent of insulin-dependent glucose transport, but do not demonstrate direct functional improvement in mitochondrial or redox status. Conclusions: HK M. aurum exerts partial anti-hyperglycemic effects in STZ-induced diabetic mice, but the associated protein changes require functional validation before its role as a postbiotic in β-cell dysfunction can be established. Full article

Background/Objectives: Trigeminal neuralgia (TN) is a debilitating neurological condition characterized by recurrent, severe pain linked to peripheral and central sensitization within trigeminal pathways. Current pharmacologic treatments are limited by inadequate efficacy or dose-limiting side effects, and botulinum neurotoxin type A (BoNT/A) has emerged as a viable option. However, its potential use in the management of TN is hampered by methodological limitations in existing studies and a lack of pivotal clinical trials. This study investigated the efficacy, optimal treatment site, preventive utility, and duration of effect of incobotulinumtoxinA (Inco/A), a BoNT/A, in a model of TN. Methods: An infraorbital nerve chronic constriction injury model was used to induce mechanical allodynia in male Sprague–Dawley rats, reproducing the trigeminal sensitization seen in TN. The effects of subcutaneous Inco/A (1, 2, and 4 U) were measured using the mechanical sensitivity (von Frey) test to evaluate the dose response, effect of injection location, potential preventive nature of treatment, and duration of benefit. Results: Inco/A produced a robust, dose-dependent reduction in mechanical allodynia, predominantly via a local mechanism of action. Both preventive and therapeutic administration of Inco/A was efficacious, with significant reduction in allodynia even when administered up to 28 days before nerve injury. The anti-allodynic effect persisted up to 56 days post-injection. Conclusions: Inco/A is highly effective in alleviating mechanical allodynia in a validated rat model of TN. The findings highlight Inco/A as a promising candidate for clinical translation in TN and related neuropathic pain syndromes and support systematic investigation in well-controlled human trials. Full article

Temporomandibular joint osteoarthritis (TMJ-OA) is a multifactorial degenerative disorder characterized by progressive cartilage degradation, subchondral bone remodeling, and chronic inflammation, leading to pain and functional impairment in affected individuals. Despite its clinical impact, effective disease-modifying treatments remain limited, highlighting the need for innovative therapeutic approaches for treating this condition in the future. This manuscript examines the biological rationale, clinical applications, and therapeutic potential of platelet-rich plasma (PRP) and injectable platelet-rich fibrin (i-PRF) in the management of TMJ-OA. As autologous platelet-derived biomaterials, PRP and i-PRF contain high concentrations of growth factors and bioactive molecules that can modulate inflammatory responses and support tissue repair. PRP is associated with a relatively rapid release of these mediators, whereas i-PRF forms a fibrin matrix that may enable a more sustained release profile. Current clinical evidence suggests that both therapies show potential to contribute to pain reduction and may facilitate improvements in mandibular function. However, substantial heterogeneity in preparation protocols, study designs, and outcome measures limits the comparability and generalizability of these findings to the general population. Overall, PRP and i-PRF represent promising, minimally invasive regenerative strategies for managing TMJ-OA. Full article

The VHL–HIF-1α–VEGF axis regulates angiogenesis and metabolism. Beyond oncology, pVHL is essential for pancreatic β-cell function and is reduced in hypercaloric diet (HCD)-induced type 2 diabetes mellitus (T2DM). This study aimed to overexpress pVHL in pancreatic tissue and evaluate its effects on blood glucose levels and the expression of proteins related to glucose metabolism in the pancreas. HCD-induced diabetic C57BL/6 and BALB/c mice received a single intrapancreatic injection of an adenoviral vector (1 × 10¹² viral particles) encoding the murine Vhlh gene (AdVHL) to induce transient pVHL overexpression. The glycemic delta (post-load glucose minus fasting) and net incremental area under the curve (niAUC) were determined on days 3, 6, 9, 12, and 15 post-treatment, as the peak in GFP overexpression (used as a surrogate reporter of transduction efficiency) was detected between days 9 and 12. Immunohistochemistry (IHC) and immunofluorescence (IF) were used to assess the expression of pVHL, HIF-1α, GLUT-1, GLUT-2, and insulin in pancreatic tissue. AdVHL treatment significantly decreased the glycemic delta and niAUC in mice with T2DM (p < 0.01). On day 15 after treatment, HIF-1α and GLUT-1 expression were markedly reduced in AdVHL-treated mice (p < 0.01), while GLUT-2 and insulin were significantly increased (p < 0.01). These results were reproduced in both mouse strains. Transient overexpression of pVHL in pancreatic tissue of mice with T2DM was associated with decreased glucose levels and changes in the expression of proteins related to glucose metabolism in the pancreas, resembling a healthier phenotype than that of mice with T2DM. These findings support an important functional role of the pVHL–HIF-1α axis in pancreatic physiology, provide a proof-of-concept for further mechanistic and translational studies, and implicate pVHL in the altered glucose metabolism observed in T2DM. Full article

Vitis coignetiae Pulliat ex Planch, commonly referred to as “meoru” in Korea (crimson glory vine), is a grape species belonging to the Vitaceae family, native to East Asia. This study investigated the protective effects of a hot water extract prepared from the vine stems of V. coignetiae (CG) in a model of CCl₄-induced acute liver injury. Mice received oral administration of CG (100, 200, and 400 mg/kg) or silymarin (200 mg/kg) once daily for 7 consecutive days, followed by intraperitoneal injection of CCl₄ (0.5 mL/kg). CG attenuated CCl₄-induced oxidative stress, as indicated by reduced hepatic malondialdehyde production and decreased 4-hydroxynonenal-positive cells. These effects were accompanied by restoration of antioxidant defense systems, including increased glutathione levels and superoxide dismutase and catalase activities, along with increased nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression. Hepatic inflammatory responses were also attenuated by CG treatment, with reductions in TNF-α, interleukin (IL)-1β, and IL-6 levels, inflammatory cell infiltration, and nuclear factor-κB (NF-κB) mRNA expression. Furthermore, CG attenuated apoptotic cell death, as evidenced by decreased cleaved caspase-3-positive and cleaved poly(ADP-ribose) polymerase (PARP)-positive cells. CG also lowered serum aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transferase levels, and alleviated hepatocellular degeneration in histopathological analysis. Collectively, these findings suggest that CG may exert protective effects against CCl₄-induced liver injury by regulating oxidative stress, inflammation, and apoptosis. Full article

Background/Objectives: Combination of antiparasitic drugs with different mechanisms of action has been suggested as an effective strategy to delay the development of parasite resistance. Considering the need to understand the pharmacological basis of drug combinations, the current study evaluated the potential pharmacokinetic (PK) interactions and the clinical efficacy (pharmacodynamic response) occurring after the subcutaneous administration of ivermectin (IVM) and levamisole (LEV), administered either as single treatments or concurrently to different groups of parasitized calves on three commercial farms (A, B and C). Methods: Forty-five (45) male calves naturally infected with gastrointestinal nematodes were randomly allocated into three groups (n = 15): IVM, treated with IVM by subcutaneous injection (0.2 mg/kg); LEV, treated subcutaneously with LEV (8 mg/kg); IVM + LEV, simultaneously treated with IVM and LEV (two subcutaneous injections at the same dose rates). Seven animals from each treated group (farm C) were randomly selected to perform the PK study. Drug concentrations were measured by HPLC. The therapeutic response (efficacy) was determined at 14 days after treatment by the fecal egg reduction test. Results: The mean area under the concentration vs time curve (AUC) for IVM obtained after administration of IVM alone (274 ± 65.1 ng.d/mL) was similar to that obtained when IVM was co-administered with LEV (295 ± 111 ng.d/mL). Likewise, mean LEV AUC values were similar after LEV administration alone (8.90 ± 2.69 µg.h/mL) or combined with IVM (9.11 ± 1.82 µg.h/mL). No adverse PK interactions were observed after the combined treatment, with similar PK parameters (p > 0.05) obtained between the single-drug and the combination-based strategies. On farm A, the overall fecal egg reductions were 38% (IVM), 99% (LEV) and 100% (IVM + LEV). While Cooperia spp. and Haemonchus spp. showed reduced susceptibility to IVM treatment, LEV demonstrated high efficacy against both genera, with only a minimal proportion of Haemonchus spp. remaining after treatment. Similarly, total fecal egg reductions were 42% (IVM), 99% (LEV) and 100% (IVM + LEV) on farm B, and 54% (IVM), 99% (LEV) and 100% (IVM + LEV) on farm C. On those farms, IVM was ineffective against Cooperia spp. and/or Haemonchus spp., while LEV failed to control Ostertagia spp. Remarkably, the combination of both molecules was the only treatment that achieved 100% efficacy against all nematode genera (Cooperia, Ostertagia, Haemonchus and Oesophagostomum spp.). Conclusions: Based on the described PK and pharmacodynamic (PD) assessments, the IVM + LEV combination appears to be a promising pharmacological option for controlling resistant gastrointestinal nematodes in cattle, with the additional potential to delay the progression of nematode anthelmintic resistance. Overall, the study provides original and robust pharmacokinetic and efficacy data that contribute to the optimization of parasite control strategies in cattle. This drug combination strategy may enhance treatment efficacy and contribute to improved parasite control in cattle production systems. Full article

Background: Trigeminal neuralgia (TN) is clinically defined, but patients presenting to tertiary practice with trigeminal-region pain are often diagnostically heterogeneous and may follow prolonged medication, dental, imaging, and procedural pathways before a stable phenotype is established. We aimed to characterize diagnostic phenotypes, secondary causes, and treatment-escalation patterns in a large retrospective tertiary-center trigeminal pain cohort derived from routine free-text clinical documentation. Methods: We conducted a retrospective single-center cohort study based on a clinical dataset containing 18,007 note fragments linked to 672 unique patient records between 12 October 2010 and 21 April 2026. A rule-based natural-language-processing-assisted chart review framework was used to identify patients with trigeminal pain and to extract documentation-derived demographic features, pain distribution, secondary causes, dental pathway variables, imaging signals, medication exposure, procedures, and outcome language. Patients were grouped into primary/classical TN, secondary TN/trigeminal pain, and dental-first or mimic pathways using predefined operational criteria. Results: A total of 455 patients met criteria for the analytic trigeminal pain cohort; 311 (68.4%) carried explicit TN terminology. Mean age was 58.7 years, median age 60 years, and 267 of 428 patients with recoverable sex data (62.4%) were women. Trigeminal branch involvement could be extracted in 351 patients (77.1%), with V2 involvement documented in 256 (56.3%), V3 involvement in 218 (47.9%), and V1 involvement in 138 (30.3%). The final NLP-derived phenotypic distribution comprised 201 primary/classical TN cases (44.2%), 146 secondary TN/trigeminal pain cases (32.1%), and 108 dental-first or mimic presentations (23.7%). MRI was documented in 384 patients (84.4%), neurovascular conflict or vascular loop in 253 (55.6%), multiple-sclerosis-related disease in 69 (15.2%), and tumor-related trigeminal involvement in 84 (18.5%). Prior dental evaluation was identified in 169 patients (37.1%), and prior dental procedures in 114 (25.1%). Carbamazepine exposure was documented in 367 patients (80.7%), pregabalin in 221 (48.6%), gabapentin in 150 (33.0%), oxcarbazepine in 116 (25.5%), and phenytoin in 73 (16.0%). At least one invasive or image-guided procedure was documented in 390 patients (85.7%), including nerve blocks/injections in 355 (78.0%), radiofrequency procedures in 126 (27.7%), balloon compression in 90 (19.8%), microvascular decompression in 113 (24.8%), and stereotactic radiosurgery in 55 (12.1%). Dental-first patients were significantly more likely to have undergone prior dental procedures (65.7% vs. 3.5% in primary/classical TN and 24.7% in secondary TN; p < 0.001), whereas secondary TN/trigeminal pain was associated with higher use of radiofrequency procedures (36.3%; p = 0.017), higher use of stereotactic radiosurgery (19.9%; p = 0.002), higher recurrence documentation (70.5%; p = 0.001), and a higher rate of complete pain relief documented at last follow-up (46.6%; p = 0.004). Conclusions: In tertiary practice, trigeminal pain is substantially broader than a formal TN label. Secondary disease and dental-first pathways account for a large fraction of referrals, and management is characterized by heavy medication burden, frequent escalation, and recurrent retreatment. A structured phenotyping approach may help convert routine clinical documentation into a clinically meaningful framework for diagnostic triage and treatment selection, although imaging and outcome variables require cautious interpretation when derived from retrospective free text. Full article

Radiotherapy remains one of the main pillars of cancer treatment and is used in more than half of all oncological patients. Despite continuous technological improvements, ionizing radiation inevitably causes damage to surrounding healthy tissues, leading to acute and chronic complications affecting multiple organs, including the skin, mucosa, heart, lungs, bones and gastrointestinal tract. Radiation-induced injuries significantly impair patients’ quality of life, limit therapeutic doses, and represent a major unmet clinical challenge. Hydrogels have emerged as promising biomaterials for managing radiation-induced damage due to their high content of water, tunable mechanics, and ability to mimic the extracellular matrix. Recent innovations have introduced functional systems, including stimuli-responsive, injectable, and bioactive hydrogels, capable of delivering antioxidants, growth factors, or living cells. Unlike traditional material-based reviews, this work proposes a novel classification framework based on the hydrogel’s mechanism of action within the pathophysiology of radiation injury. We evaluate how specific designs, such as ROS-scavenging matrices, barrier-forming injectable shields, and bioactive delivery vehicles, address distinct phases of inflammation and fibrosis. By providing a comprehensive overview of radiation-induced injuries across different organs, this review summarizes current hydrogel-based strategies for both prevention and therapy. We highlight the potential of these mechanistically aligned systems to protect healthy tissues, suppress chronic inflammation, and promote effective tissue regeneration. Full article

This study aimed to develop antibacterial polyphenol–chitosan hydrogel dressings and, more importantly, to compare how three structurally distinct low-cost natural polyphenols—protocatechuic acid (PCA), gallic acid (GA), and tannic acid (TA)—regulate hydrogel performance within the same chitosan platform. PCA, GA, and TA were incorporated into chitosan to obtain the corresponding hydrogels, denoted CS-PCA, CS-GA, and CS-TA. Scanning electron microscopy confirmed that all formulations possessed a three-dimensional porous network. Rheological characterization revealed favorable viscoelastic behavior for all polyphenol-containing hydrogels, with CS-TA showing the highest mechanical strength in the present system. The hydrogels also exhibited pH-responsive swelling, good tissue adhesion, self-healing ability, and injectability. In vitro antibacterial assays demonstrated activity against both Gram-positive and Gram-negative microorganisms, with CS-TA showing the most favorable overall antibacterial performance under the tested conditions. In a rat full-thickness wound model, hydrogel treatment accelerated wound closure, while H&E staining indicated enhanced granulation tissue formation, collagen deposition, and reduced inflammatory cell infiltration. Collectively, these findings support the use of polyphenol–chitosan composite hydrogels as promising wound-dressing candidates and highlight the value of a side-by-side comparison of PCA, GA, and TA for understanding structure–property–function relationships in this class of materials. Full article

Background and Aims: Automated insulin delivery (AID) systems are standard of care for type 1 diabetes mellitus (T1DM). Tubeless AID systems may improve treatment acceptance, but real-world European data in patients transitioning from multiple daily injections (MDI) or open-loop patch pump therapy are limited. This study evaluated real-world glycemic, safety, and quality-of-life (QoL) outcomes after transition to a tubeless automated closed-loop system (Omnipod 5^®, OP5^®). Research Design and Methods: In this prospective, multicenter observational study, adults with T1DM transitioned from MDI or open-loop continuous subcutaneous insulin infusion to OP5^® and were followed for 180 days. Continuous glucose monitoring-derived metrics and validated patient-reported outcome measures were assessed. Subgroup analyses were performed by prior therapy. Results: Of the 94 enrolled participants, 88 completed the study. At 180 days, HbA1c decreased from 7.5% to 7.1% (p < 0.001), and time in range increased from 59.0% to 68.0% (p < 0.001) without increased hypoglycemia. The proportion achieving TIR_70–180 ≥ 70% rose from 12.5% to 43.2%. Improvements were greater among prior MDI users. Treatment satisfaction and diabetes-related QoL improved significantly. The mean time in automated mode was 90.9%. Conclusions. Transition to tubeless AID significantly improved glycemic and psychosocial outcomes, supporting its effectiveness in routine clinical practice. Full article

Background: Knee osteoarthritis (KOA) is a major cause of disability worldwide, and adipose-derived stromal vascular fraction (SVF) has emerged as a potential regenerative treatment to modify disease progression. Objective: This study aimed to assess the effectiveness of autologous adipose-derived stromal vascular fraction (SVF) through intra-articular injection to treat early-stage knee osteoarthritis (KOA). Materials and Methods: This multicenter observational study (2019–2023) included adults aged 18–65 years with radiographically confirmed knee osteoarthritis. Patients were assigned to one of two groups through a retrospective, non-randomized process based on the actual treatment received during their clinical follow-up. Group T received intra-articular adipose-derived stromal vascular fraction (SVF) injections, while Group C received conservative treatment with non-steroidal anti-inflammatory drugs (NSAIDs) only. SVF was obtained from abdominal adipose tissue using a standardized closed-system device and injected intra-articularly. Pain and functional outcomes were assessed using the Visual Analog Scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline and at 1, 3, 6, 9, and 12 months. Results: Sixty-seven patients (41 SVF, 26 controls) were included, with comparable baseline characteristics (all p > 0.05). Preoperative VAS was lower in the SVF group (7.44 ± 1.44 vs. 8.31 ± 1.09; p = 0.029). At 12 months, VAS significantly decreased to 3.77 ± 1.49 in the SVF group, whereas it increased to 8.85 ± 0.67 in controls (p < 0.001). Similarly, baseline WOMAC scores were lower in the SVF group (62.6 ± 21.7 vs. 76.8 ± 8.76; p = 0.004). At 12 months, WOMAC improved to 29.4 ± 15 in the SVF group but worsened to 87.6 ± 3.21 in controls (p < 0.001). Within-group improvements were significant only in the SVF group (p < 0.001). No procedure-related complications were observed. Conclusions: The autologous adipose-derived stromal vascular fraction is an effective treatment option for early-stage KOA patients. However, a prospective, randomized, controlled study is warranted. Full article

Surgical intervention is a primary treatment for osteosarcoma, often resulting in a tumorous bone defect with an irregular shape. Postoperative management is essential to minimize tumor recurrence risks and promote bone regeneration. To address these issues, we developed a multifunctional injectable, rapidly photo-curable hydrogel composed of gelatin methacryloyl/carboxymethyl chitosan/hyaluronic acid (GelMA/CMCS/HA), modified with vanadium-doped mesoporous bioactive glass (VMBG). The exceptional injectability enables seamless adaptation to irregular bone defects, offering a significant advantage over preformed implants, while the rapid photocurability of the hydrogel ensures stable fixation within minutes, thereby reducing potential risks during surgery. Furthermore, this platform exhibits dual therapeutic efficacy, characterized by antitumor activity and osteogenic induction. In vitro assessments demonstrated that V(V)/V(IV) valence cycling-driven ROS generation mediated its potent antitumor efficacy. Additionally, concurrent enhancement of alkaline phosphatase activity and osteogenic marker expression validated its osteogenic potential. The CMCS incorporation promoted healing at the defect site, while the HA addition created binding sites for cell adhesion and growth, thereby improving scaffold bioactivity. Collectively, this study presents the development and validation of a multifunctional GelMA/CMCS/HA hydrogel, highlighting its dual capability for bone regeneration and tumor suppression within tumor-associated bone microenvironments. Full article

Mesenchymal stromal/stem cells (MSCs) are increasingly investigated as intra-articular therapies for equine osteoarthritis (OA), although most studies have focused on allogeneic or combination-based approaches. Evidence supporting the use of autologous MSCs as a stand-alone treatment remains limited. The present study evaluated the safety and clinical evolution following intra-articular administration of autologous muscle-derived MSCs (mdMSCs) in horses with naturally occurring chronic OA. Thirteen horses with confirmed clinical disease were included. Each affected joint received a single injection, with the administered cell dose adapted to joint size (1 × 10⁷ or 2 × 10⁷ cells). Clinical assessments were conducted at baseline and at 6 and 12 weeks post-treatment using the American Association of Equine Practitioners (AAEP) lameness scale, together with a joint inflammation score and a composite total clinical score (TCS). Clinical scores decreased over time, with statistically significant improvements observed at both follow-up time points. Seven of thirteen horses met the predefined responder criteria based on AAEP improvement, including complete resolution of lameness in several cases. The treatment was well tolerated, with only mild and transient local reactions that resolved without intervention. These results indicate that intra-articular administration of autologous mdMSCs is associated with clinically relevant improvement in horses with chronic OA. Full article