Search Results (305)

Corneal endothelial dysfunction is a leading cause of vision impairment globally, traditionally managed through donor-dependent keratoplasty procedures. However, limitations in donor tissue availability, surgical complexity, and long-term graft survival have prompted the development of cell-based regenerative therapies. Among these, corneal endothelial cells (CECs) injection therapy has emerged as a minimally invasive alternative, offering the potential to restore endothelial function. This review provides a comprehensive analysis of recent advances in bioengineering strategies for CECs therapy, including cell sourcing from donor tissue, pluripotent stem cells, and transdifferentiated somatic cells; optimization of culture conditions and substrates; and delivery protocols that enhance cell adhesion and survival. We further examine clinical trial outcomes and propose future directions for clinical translation. The convergence of cell biology, biomaterials engineering, and translational medicine positions CECs injection therapy as a transformative solution to corneal blindness. Full article

Thirty dogs were equally assigned to a platelet-rich plasma group (PRPG), a photobiomodulation group (PBMTG), or a combined therapies group (PRP + PBMTG). Response to treatment was evaluated with weight-bearing distribution and different owner-reported outcome measures. Evaluations were conducted at 0, +8, +15, +30, +60, +90, +120, +150, and +180 days after the initial treatment. After the first 180 days, a crossover was performed, and a second 180-day follow-up was conducted. A second cross-over was performed, with a final 180-day follow-up. Nineteen males and eleven females were included, with a mean age of 9.4 ± 2.7 years and a body weight of 26.6 ± 3.8 kg. Six hips were classified as mild, eighteen as moderate, and six as severe. All treatments were able to produce clinically significant improvements in different evaluation modalities, with varied degrees of magnitude and duration. At the last follow-up, the combination of PRP and PBMT had a greater effect, showing a significant difference compared to the isolated treatments, with a moderate to large effect size. Kaplan–Meier estimators showed that PRP + PBMTG had more extended periods with better results. PRP and PBMT could improve objective outcomes and client-reported outcome measures in dogs with OA. Their combined use leads to greater, longer-lasting, clinically significant improvements. Full article

Using Medline and Scopus as search engines, we identified reports of 10 clinical studies (published up to 1 September 2025) on botulinum neurotoxin therapy for hereditary spastic paraplegia (HSP). Nine studies were conducted in adults and one in children. Only one of the ten studies was double-blind and placebo-controlled. The search strategy included only articles published in English and articles providing basic information such as the type of the study, type and dose of the toxin and results of the treatment. Articles not in English, case reports and review articles were excluded. A total of 258 patients were included across all studies. The injected toxin in the open-label studies was botulinumtoxin-A (Botox or Dysport or Xeomin), whereas in the blinded study, the investigators used Prosigne. All open-label studies, which used FDA approved botulinumtoxin-A neurotoxins, demonstrated a degree of motor and non-motor improvement, whereas treatment with Prosigne did not improve patients’ function. The possible reasons for this discrepancy between the blinded study and the open-label studies are discussed. We found no studies on the effect of BoNTs on bladder dysfunction in HSP. There is a need for double-blind, placebo-controlled studies assessing the efficacy of FDA-approved botulinum neurotoxins in children and adults affected by hereditary spastic paraparesis. Such studies should also investigate the effect(s) of early botulinum neurotoxin therapy in this disorder. The novelty of this review is that it represents a comprehensive and critical literature review on this subject, with no other studies of this kind published previously. It also includes data not present in previous reviews of this subject. Full article

Glaucoma is a leading cause of irreversible blindness, and animal models are essential for studying its pathophysiology and testing therapeutic strategies. In this study, a novel hydrogel-based approach was developed and evaluated to induce experimental glaucoma in mice, using composites of hyaluronic acid (HA) and the self-assembling peptide fluorenylmethoxycarbonyl-diphenylalanine (FmocFF). Two formulations with different HA-to-FmocFF ratios were injected either intracamerally or intravitreally in C57BL/6 mice. Intraocular pressure (IOP) was monitored over 21 days, and retinal tissues were analyzed histologically and immunohistochemically. Significant IOP elevation was observed in one hydrogel formulation (Mixture B), yet without detectable retinal ganglion cell loss. A significant reduction in retinal ganglion cell (RGC) density, independent of IOP changes or injection site, was observed in Mixture A. Histological staining confirmed successful delivery and localization of the hydrogel in the anterior chamber, and no evidence of gliosis, microglial activation, or increased apoptosis was revealed by immunostaining. Collectively, these data position the HA-FmocFF hydrogel as a proof-of-concept that advances glaucoma model development, although it does not yet recapitulate the full disease. This model may facilitate future studies of neuroprotection and disease-modifying therapies in glaucoma without confounding inflammatory responses. Full article

Background/Objective: To test the feasibility of a mixed-phase, pilot, placebo-controlled, double-blind trial of mistletoe therapy (MT) with an embedded qualitative study in the UK National Health Service (NHS) setting. Methods: The aim was to recruit 45 patients via an NHS oncology centre with a diagnosis of early or locally advanced breast cancer. Participants were allocated to Iscador^® Malus, Iscador^® Pinus, or physiological saline (placebo). Diaries and quality-of-life questionnaires were administered. Qualitative interviews were conducted with participants, oncologists, and nurses. Feasibility was assessed by recruitment, retention, adherence, blinding, and safety. Results: Sixty-seven patients were approached between August 2019 and March 2020, 15 gave consent, 14 participants were randomised, and 2 withdrew during the trial. Ten participants and five staff were interviewed. Barriers to recruitment were the additional treatments/time, extra injections, and the possibility of placebo allocation. Adherence was very good whilst the participants were on the study therapy. Diaries and interviews indicated that 11/14 participants struggled with injections and skin reactions. There were 22 adverse events due to the MT, related to the injections or skin reactions. Conclusion: This pilot study examined the feasibility of conducting a randomised placebo-controlled, double-blind trial of mistletoe therapy for breast cancer patients within the UK NHS. The results describe the challenges and achievements of recruitment, retention, adherence, blinding, and safety in this context. Full article

Purpose: Cadaveric dissection is a cornerstone of neurosurgical education, providing trainees with a realistic 3D understanding of anatomy and a safe environment to practice surgical approaches. A preservation technique was developed that merges the advantages of fresh-frozen and embalmed cadavers, maintaining tissue realism while enhancing durability. This approach preserves flexibility and natural color, improves anatomical detail, and creates a safe, long-lasting model ideal for neurosurgical training. Methods: Four specimens were thawed, cannulated, and irrigated before implementing a protocol consisting of low concentration formaldehyde with glycerol and ethanol for extended preservation. The specimens were prepared for both neurosurgery training and educational purposes, and their condition was evaluated with a semi-quantitative scale. Each specimen was evaluated independently by two raters, blinded to the time-point, using a semi-quantitative scale anchored to predefined criteria (0–3 per domain). Inter-rater reliability was calculated using the intraclass correlation coefficient (ICC [2,k]) for continuous scores and Cohen’s κ for categorical agreement. Results: Over nine years of intermittent use, the specimens remained in good condition: tissues retained sufficient softness for dissection, injected vessels stayed vivid in color, and no foul odor or microbial growth was observed. The evaluation employed a semi-quantitative scale, with results ranging from 11/14 to 14/14. The mean values demonstrate stable tissue quality over time, with only minor variations in color and perfusion. The inter-rater reliability was high (ICC = 0.91; κ = 0.88). Conclusions: The preservation method leverages the strengths of both fresh-frozen and embalmed models. The results suggest feasibility of long-term reuse, although further quantitative validation is needed. Full article

Age-related macular degeneration (AMD) represents a leading cause of irreversible blindness in the elderly, primarily by choroidal neovascularization (CNV) leakage. While intravitreal injections of anti-angiogenic antibodies (e.g., aflibercept) provide clinical benefits, their short half-life necessitates frequent administrations, potentially causing ocular infections or retinal detachment. There is an urgent need for effective antibody delivery systems. Mesoporous silica nanoparticles (MSN) have emerged as promising nanocarriers due to their tunable porosity, surface modifiability, and biocompatibility, though their application in ophthalmology for antibody delivery remains underexplored. We developed two MSN carries: spiky mesoporous silica nanospheres (S-MSN) without amino groups and amine-functionalized hollow dendritic mesoporous silica nanospheres (A-HDMSN). Characterization revealed that A-HDMSN exhibited superior properties, including a larger surface area (550.32 vs. 257.72 m²/g), larger mesoporous pore size (17 vs. <10 nm), and 5.28 times higher drug loading capacity (286.31 ± 8.14 vs. 54.26 ± 3.61 μg/mg) compared to S-MSN (n = 3, p < 0.001), attributable to pore size effects and hydrogen bonding. FITC-labeled A-HDMSN demonstrated efficient uptake by retinal pigment epithelial cells (ARPE-19). Notably, A-HDMSN loaded with Aflibercept (A-HDMSN@Afl) showed significant inhibitory effect on VEGF-induced cell migration even 10 days after drug release in vitro, indicating a favorable sustained-release effect of the drug. These findings highlight A-HDMSN as a promising antibody delivery platform that could extend clinical dosing intervals, offering potential for improved AMD management. Full article

Sludge dewatering remains a resource-intensive process, often constrained by high residual moisture content and inefficient chemical conditioning. Conventional systems typically rely on fixed polymer dosages and predetermined filtration pressures, which are unable to respond to variations in sludge characteristics, resulting in inconsistent and suboptimal performance. In this study, a real-time control system for municipal wastewater sludge dewatering was developed to dynamically regulate coagulant dosing and filtration pressure based on continuous monitoring of critical sludge parameters, including total solids (TS), viscosity, sludge temperature, and pH change following coagulant addition. The control logic, derived from empirical correlations between sludge dewaterability metrics such as time-to-filter (TTF) and capillary suction time (CST) and operational variables, enables adaptive adjustment of polyoxyethylene alkyl ether (POAE) injection and pressing conditions. Implementation of this system achieved a final cake moisture content of approximately 63% after 60 min of filtration, substantially lower than the ~84% moisture observed under static conditions. Real-time flux feedback facilitated timely pressure escalation (from 15 to 20 bar to 25–30 bar), improving water removal efficiency while avoiding premature cake blinding. The pH drop (~0.7 units) post-polymer addition served as a practical indicator of adequate flocculation, supporting dose optimization and minimizing chemical waste. The proposed system demonstrated enhanced dewatering performance, reduced polymer consumption, and greater operational robustness compared to conventional approaches. These findings highlight the potential of integrated sensor-based control to advance sludge treatment technologies by promoting smarter, adaptive, and resource-efficient dewatering operations. Full article

Intra-articular injections form a substantial element of the temporomandibular joint disorder (TMD) therapy. Given the role played by IL-1β in pathology, the use of autologous conditioned serum (ACS) is well-founded. Despite years of effective use in different locations, data regarding the intra-articular administration of ACS in TMD is scarce, and the strategy itself is not routinely applied. This study aims to provide preliminary evidence on the therapeutic efficacy of administering intra-articular ACS in treating TMD. Patients with TMD who received intra-articular ACS were included. More invasive co-interventions, such as arthroscopy, were excluded. Final searches were conducted on 17 June 2025, using five databases (ACM, BASE, DOAJ, PubMed, and SciELO). Risk of bias was evaluated using the RoB 2 tool. The results were tabulated. Only one study met the inclusion criteria. When compared to dextrose prolotherapy in internal TMD, ACS therapy resulted in greater improvement in mouth opening, pain, and joint-sound reduction. The small sample size, head-to-head design, and limited blinding suggest a highly cautious interpretation of the findings. ACS is a promising, but still experimental, therapeutic strategy addressing critical mechanisms in TMD. However, the currently available data is insufficient to confirm the effectiveness and safety of such an approach, and further high-quality studies are needed. This study received no funding. PROSPERO registration number: CRD420251069310. Full article

Chronic kidney disease (CKD) is a common and serious condition in felines. Accordingly, several cell therapies have been studied over the past decades for effective treatments. This study aimed to develop a new lineage of renal progenitor cells for use in cats with CKD. Metanephric and mesonephric progenitor cells were obtained from mesonephros and metanephros tissues of feline conceptuses at four distinct gestational stages. The cultured cells were characterized by their morphology, tumorigenic potential, immunophenotype determined by flow cytometry, and differentiation potential. We then conducted a pilot study in CKD-affected cats, comparing intraperitoneal injections of cultured metanephric progenitor cells (n = 4) to a placebo solution (n = 3). All four cell types exhibited adhesion and colony formation, but showed no tumorigenic potential. Cells tested positive for renal progenitor markers (CD117, Nephron, and WT1), confirming their identity. Treated cats showed no statistically significant differences (p ≤ 0.05) in any of the data analyzed. However, caregivers reported a voluntary increase in appetite after cell administration. Veterinarians confirmed this information during double-blind evaluations conducted after treatment. Although this data are qualitative, no clinical deterioration was observed in cats. Our results suggest that this new lineage of renal progenitor cells did not induce immediate adverse effects, thus supporting its potential for use in cell-based therapies. However, further studies are needed to evaluate its efficacy in treating renal diseases. Full article

Early-stage knee osteoarthritis (knee OA) lacks effective regenerative therapies. This study aimed to compare the cartilage regenerative effects, clinical efficacy, and safety of intra-articular injections of autologous adipose-derived mesenchymal stem cells (ADSCs) versus hyaluronic acid (HA). Forty-eight patients with early knee OA were enrolled in a prospective open-blinded multi-center study at Suranaree University of Technology Hospital and Phramongkutklao Hospital. Participants were randomized into either the ADSC or HA group. Primary outcomes included MRI-based cartilage lesion volume, synovial thickness via ultrasound, and WOMAC scores over 6 months. MRI results revealed significant and progressive cartilage regeneration in the ADSC group. In particular, medial femoral cartilage lesion volume decreased by 50.06 mm³, whereas the HA group showed an increase of 36.44 mm³. Synovial thickness also declined significantly in the ADSC group at 3 and 6 months. Both groups demonstrated reduced symptoms, but the ADSC group achieved superior and sustained improvements in WOMAC pain, stiffness, and function scores throughout the 6-month follow-up. The clinical benefits were consistent and more pronounced compared with HA. No serious adverse events occurred. In conclusion, intra-articular ADSC injections show superior cartilage restoration on MRI and better clinical outcomes than HA injection, making them a promising treatment for early-stage knee OA. Full article

Background: Respiratory syncytial virus (RSV) poses a significant global health threat, particularly to children and the elderly. While progress has been made in RSV vaccine development, gaps remain, especially in protecting the elderly population. BARS13, a recombinant non-glycosylated G protein-based RSV vaccine, has shown promise in preclinical and Phase 1 studies. This phase II trial sought to determine whether escalating doses of BARS13 could enhance immune responses while maintaining safety and tolerability in healthy older adults aged 60–80 years. Methods: This study employed a rigorous randomized, double-blind, placebo-controlled design involving 125 participants across two Australian centers. Participants were randomized in a 3:1 (vaccine–placebo) ratio for Cohorts 1–2 (30 active, 10 placebo each) and a 2:1 ratio for Cohort 3 (30 active, 15 placebo). Cohort 1 (low dose) received 10 µg rRSV-G + 10 µg CsA in one arm + a placebo in the other (Days 1 and 29); Cohort 2 (high dose) received 10 µg rRSV-G + 10 µg CsA in both arms (20 µg total per dose, Days 1 and 29); Cohort 3 (multi-dose) received the same dose as that of Cohort 2 but with a third dose on Day 57. The placebo groups received IM injections in both arms at matching timepoints. The primary endpoints included safety and tolerability assessments, while the secondary endpoints evaluated the RSV G protein-specific IgG antibody concentrations using enzyme-linked immunosorbent assays (ELISAs). Statistical analysis was performed on both the safety and immunogenicity populations. Results: BARS13 was well-tolerated across all cohorts, with no serious adverse events (SAEs) related to the vaccine. The most common adverse events were mild local reactions (pain and tenderness) and systemic reactions (headache and fatigue), which resolved within 24–48 h. Immunogenicity analysis demonstrated a dose-dependent increase in the RSV G protein-specific IgG geometric mean concentrations (GMCs). Cohort 3, which received multiple high-repeat dose administrations, showed the highest immune response, with the IgG GMC rising from 1195.4 IU/mL on Day 1 to 1681.5 IU/mL on Day 113. Response rates were also the highest in Cohort 3, with 86.2% of participants showing an increase in antibody levels by Day 29. Conclusions: BARS13 demonstrated a favorable safety profile and strong immunogenicity in elderly participants, with a clear dose-dependent antibody response. These results support further development of BARS13 as a potential RSV vaccine candidate for the elderly. Further studies are needed to evaluate the long-term efficacy and optimal dosing schedule. Full article

Glaucoma is the leading cause of irreversible blindness worldwide, and the Ahmed Glaucoma Valve (AGV) implant is one of the most commonly performed surgeries to prevent glaucoma-related visual impairment. Mitomycin C is an anti-fibrotic agent that may prevent failure of AGV. This is a retrospective case–control study to evaluate surgical outcomes for patients undergoing AGV with adjunct mitomycin C (MMC) injections compared to those without MMC. Among the 142 eyes, 50 received adjunct MMC compared to 92 without MMC injections. IOPs at post-operative months 1, 3, and 6 were significantly lower in the MMC eyes (9.40, 12.01, 12.63 mmHg) compared to the No-MMC eyes (16.86, 15.87, 15.65 mmHg; p < 0.01). The number of post-operative glaucoma medications for the MMC group was lower at 1, 3, and 6 months (0.3, 0.4, 0.59) compared to the No-MMC group (0.7, 0.97, 1.05; p < 0.05). The difference in IOP and the number of medications was not statistically significant by 12 months. Adjunct MMC was associated with more transient hypotony but no long-term complications. These findings suggest that adjunct MMC improves short-term but not long-term surgical outcomes in AGV glaucoma implants. Full article

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness worldwide, primarily due to pathological choroidal neovascularization (CNV). Our study investigates a chemically modified heparin derivative as a novel strategy to selectively modulate angiogenic signaling, offering a reduced anticoagulant risk and preclinical support for AMD treatment. We explored the therapeutic potential of 6-O-desulfated heparin (Hep-6Od) as an antiangiogenic agent with diminished anticoagulant activity. Synthesized via selective 6-O-desulfation and characterized using nuclear magnetic resonance (NMR), Hep-6Od demonstrated safety in retinal pigment epithelial cells with no cytotoxic effects at various concentrations. In vitro, the compound significantly inhibited endothelial cell proliferation, migration, and capillary tube formation. Differential scanning fluorimetry (DSF) assays confirmed molecular interaction between Hep-6Od and fibroblast growth factor 2 (FGF-2), suggesting interference with pro-angiogenic signaling pathways. In vivo, a laser-induced CNV model in lean Zucker rats showed a dose-dependent reduction in neovascular lesion areas after an intravitreal Hep-6Od injection. Compared to unfractionated heparin, Hep-6Od exhibited reduced anticoagulant effects in PT and aPTT assays while maintaining robust antiangiogenic properties. These findings support Hep-6Od as a promising alternative to anti-vascular endothelial growth factor (VEGF) therapies for AMD treatment, potentially expanding current retinal vascular disease interventions. The results underscore its potential to transform AMD management, pending further clinical validation and awaiting confirmation in further studies. Full article

Introduction: Fungal endophthalmitis (FE) is a rare but serious intraocular inflammatory disorder, resulting from an infection of the vitreous cavity from either endogenous or exogenous components that ultimately results in blindness. This current research study aims to elucidate the histological effects of the intravitreal injection of the maximum safe dosage of voriconazole and micafungin on the retina and investigate potential histological alterations after the double and combined administration of voriconazole and micafungin. Methodology: Nine New Zealand Albino Rabbits were randomly assigned into three groups (V2, M2, and VM), and in each, voriconazole, micafungin, and a combination of the two medications were administered respectively. After the administration of the antifungal agents, the animals were sacrificed and their retinas were retrieved and studied under optical and electron microscopes. The immunohistochemical markers TNF-a and IL6 were also studied. Results: TNF-a was positive in the VM group, as it was found to be mildly positive in the presence of apoptotic cells in the ganglion cell layer. Conclusions: This study revealed voriconazole has a greater toxicity in a multi-dosage administration. However, micafungin revealed a greater toxicity than voriconazole from the extent of the lesions observed. Full article