Search Results (5,830)

Immune-mediated inflammatory diseases (IMIDs) arise from interactions among genetic susceptibility, epithelial barrier function, microbiota, diet, and other environmental exposures. Modern diets influence mucosal immunity not only through fibre intake, food processing, and microbiota composition, but also through a less explored exposure layer: plant-derived molecules with potential immune activity. Crop breeding, intensive agriculture, global trade, gluten-free substitutes, and plant-based food technologies have changed the spectrum, dose, concentration, and matrix in which plant defence proteins, antinutritional factors, endogenous toxicants, and novel plant antigens reach the intestinal surface. In this structured, hypothesis-generating narrative review, we propose dietary adjuvanticity as a mechanistic framework for considering how selected food-derived molecules may amplify mucosal immune responsiveness, modify antigen presentation, disturb barrier function, or lower tolerance thresholds without necessarily acting as classical autoantigens. The framework differs from general food-derived immunomodulation, nutritional exposomics, and diet-microbiota-host interaction models by focusing specifically on adjuvant-like immune amplification at the intestinal mucosa. The ASIA concept is used only in Shoenfeld’s functional sense, as an analogy for exogenous immune amplification through innate activation, danger signalling, bystander activation, epitope spreading, and loss of tolerance in susceptible hosts; it is not applied as a dietary diagnosis. Wheat amylase-trypsin inhibitors, gluten epitopes, lectins, potato glycoalkaloids, saponins, quinoa prolamins, emerging legume proteins, L-canavanine, and tolerance-promoting plant substrates are discussed with explicit separation of established clinical evidence, strong mechanistic evidence, preclinical/ex vivo evidence, and speculative disease-modifier hypotheses. Overall, plant-derived exposures are best interpreted as potential modifiers within the IMID exposome, not as primary causes of autoimmunity. Testing this model will require defined exposures, food-matrix and processing studies, biomarkers of barrier and immune activation, patient stratification, and controlled human studies. Full article

Background/Objectives: White-light cystoscopy remains central to bladder cancer detection and surveillance, but diagnostic uncertainty persists in detecting flat lesions, particularly carcinoma in situ, distinguishing inflammatory mimics, and targeting biopsies. Optical spectroscopy and spectral imaging may provide objective tissue information beyond visual inspection. This scoping review mapped the diagnostic evidence and translational readiness of these technologies. Methods: A scoping review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). PubMed, Embase and Web of Science were searched from inception to 31 July 2026. Eligible articles evaluated wavelength-dependent optical signals directly in human bladder tissue in clinically relevant in vivo or ex vivo settings. Related articles with the same, overlapping or expanded datasets were grouped into study families. Results: Forty-seven articles were organised into 39 study families. Raman spectroscopy showed the clearest progression from ex vivo discrimination to in vivo cystoscopic feasibility and device development. Fluorescence and reflectance provided early in vivo evidence, although specificity was often limited by inflammation and benign changes. Infrared and near-infrared techniques remained mainly specimen-based, while multimodal systems were evaluated mostly ex vivo. Evidence for spectral imaging was limited, and no clinically integrated endoscopic hyperspectral-imaging study meeting the criteria was identified. Conclusions: Optical spectroscopy and spectral imaging show diagnostic potential for bladder cancer tissue characterisation, but evidence remains heterogeneous and insufficient for routine implementation. Among the included techniques, Raman spectroscopy appears most translationally mature, whereas wide-field spectral imaging remains underdeveloped. Future studies should prioritise prospective in vivo evaluation, standardised acquisition, histopathological correlation, external patient-level validation and clinically meaningful endpoints. Full article

Introduction: Mechanical loading has been shown to accelerate bone growth in healthy mice, but if this is the case also in growth suppressed animals with an inflammatory condition remains unexplored. To address this, we explored the potential for mechanical loading to stimulate longitudinal bone growth under conditions of chronic inflammation. Methods: A transgenic mouse model overexpressing human tumor necrosis factor (huTNFTg) was used to mimic chronic inflammation. Six-week-old animals were exposed to daily mechanical loading, applied laterally to the right knee joint, 5 times per week for 4 weeks while bone growth was monitored weekly. The contralateral side was sham-loaded and served as an internal control. At the endpoint, growth plate morphology was assessed. For mechanistic studies, fetal rat femur bones were cultured ex vivo with cytokines added for 12 days while mechanical loading was applied every 2–3 days. Results: Mechanical loading stimulated femur bone growth, not only in wild-type controls but also in huTNFTg mice. Growth plate morphometric analyses revealed reduced growth plate height and hypertrophic zone heights in huTNFTg mice, and mechanical loading was able to counteract these changes. Ex vivo studies in cultured femur bones showed that mechanical loading can partially prevent cytokine-induced bone growth suppression, suggesting that the effect is locally mediated, rather than systemically. Conclusions: Our in vivo and ex vivo data showed that mechanical loading locally stimulates bone growth even when exposed to inflammatory cytokines. These findings suggest that mechanical loading may have a beneficial role in regulating bone growth under chronic inflammatory conditions. Full article

Background/Objectives: Ocular surface inflammation has been identified as a key causative factor for dry eye. The current study investigates the feasibility, safety, and efficacy of fenofibric acid (FFA) as a topical eye drops in controlling ocular surface inflammation. Methods: FFA was tested for its dissolution profile and its cytotoxicity in vitro, and its permeability through ocular surface tissues was tested ex vivo. A safe dose was tested on the Sprague–Dawley (SD) rat eye as an eyedrop for ocular safety and ocular pharmacokinetics. The efficacy was tested on a benzalkonium chloride (BAC)-induced dry eye model in the SD rats. The outcome measurements were analyzed against the untouched contralateral eyes of the animals. Results: The study found that FFA had a similar dissolution profile in PBS (phosphate-buffered saline) as is in saline; however, the saturated concentration in PBS was 81 times higher. FFA had an IC50 (half maximal inhibitory concentration) of 282.4 µM on HCECs (human corneal epithelium cells). The FFA permeation rate for the cornea was 1.77 × 10⁻⁶ µg/cm²/min, 4.95 × 10⁻⁶ µg/cm²/min for the conjunctiva, and 11.32 × 10⁻⁶ µg/cm²/min for the complex of the sclera/choroid. A regimen of twice-a-day eyedrops (500 µg/mL) demonstrated good ocular safety and therapeutic efficacy on the BAC-induced dry eye model in SD rats, with significant effects on the reduction in corneal edema and on preventing the loss of goblet cells from dry eye pathology. Conclusions: These findings strongly suggest that FFA eye drops at a concentration of 500 µg/mL may effectively control ocular surface inflammation and relieve dry-eye discomfort. Full article

Background: Accurate three-dimensional positioning of dental implants is fundamental for long-term prosthetic success. While static guided surgery and traditional dynamic navigation present intrinsic limitations related to physical bulk or hand–eye coordination (the “look-away” phenomenon), Augmented Reality (AR) via Head-Mounted Displays (HMDs) promises to overcome these barriers by superimposing virtual holograms directly onto the surgical field. Objectives: The aim of this scoping review is to map the existing literature to evaluate the positioning accuracy, workflow efficiency, and ergonomic/technical barriers of HMD-based AR navigation systems in implant dentistry. Methods: A systematic search was conducted across the PubMed, Scopus, Web of Science, and Cochrane Library databases, following the PRISMA-ScR guidelines. In vitro, ex vivo, and clinical studies utilizing AR headsets (e.g., HoloLens) for implant guidance, reporting quantitative data on accuracy and/or qualitative data on usability issues, were included. Results: Eleven studies were included (7 in vitro, 1 ex vivo, 3 clinical). Accuracy showed a strong dependence on case complexity: for standard implants, the mean error at the entry point ranged between 0.33 and 1.51 mm, which is comparable to s-CAIS techniques. However, in complex scenarios (zygomatic implants), significant deviations were reported (up to 5.64 mm and 9.60°). The main barriers to routine adoption identified include tracking instability due to line-of-sight interruption, device weight, and the vergence–accommodation conflict. Conclusions: AR dynamic navigation demonstrates promising potential. Nevertheless, current evidence relies predominantly on in vitro studies that fail to fully replicate real-world surgical complexities. Persistent technical and ergonomic barriers, such as tracking instability and hardware limitations, indicate that the technology remains largely in a preclinical phase and is not yet suitable for routine clinical application. Further advancements toward markerless tracking systems, lighter headsets, and rigorous in vivo trials are required. Full article

Crinum amoenum Roxb. ex Ker Gawl. (C. amoenum) is traditionally used in Nepal, but its antidiabetic potential remains insufficiently validated. This study characterized the 80% (v/v) ethanol bulb extract of C. amoenum and evaluated its antioxidant, α-amylase inhibitory, hypoglycemic, molecular docking, molecular dynamics (MD) simulation, and ADMET profiles. The ethanolic bulb extract was evaluated through phytochemical screening, thin-layer chromatography, total phenolic content (TPC), total flavonoid content (TFC) estimation, LC-MS analysis, antioxidant assays, α-amylase inhibition assays, acute toxicity testing, and hypoglycemic/oral glucose tolerance test (OGTT) studies in Wistar rats. Lycorine, pratorinine, and palmatine were docked against α-amylase (PDB ID: 5U3A) and GLP-1R (PDB ID: 6GB1), followed by 200 ns MD simulations and ADMET prediction. Qualitative analysis of the extract was positive for flavonoids, phenolic compounds, tannins, saponins, alkaloids, and carbohydrates, and a positive Salkowski reaction indicated the presence of constituents occurring in glycosidic form. The TPC was 173.38 ± 1.22 mg GAE/g, and the TFC was 314.58 ± 0.09 mg QE/g. LC-MS tentatively annotated lycorine, pratorinine, and palmatine based on retention time, m/z values in positive-mode electrospray ionization, and comparison with previously reported spectral information. The extract showed DPPH scavenging activity (IC₅₀: 90.98 μg/mL) and strong α-amylase inhibition (IC₅₀: 49.31 μg/mL) compared with acarbose (IC₅₀: 51.51 μg/mL). No deaths were observed following oral administration at 5000 mg/kg to rats. The 500 mg/kg dose produced the greatest hypoglycemic response, reducing blood glucose by 35.78% at 120 min in non-diabetic Wistar rats and by 19.21% at 60 min in glucose-loaded rats. Among all the compounds tested, pratorinine demonstrated the highest docking affinity with α-amylase (−8.2 kcal/mol; ASP300) and GLP-1R (−7.0 kcal/mol; GLY132). MD simulation supported greater stability of the α-amylase complex, and ADMET prediction identified pratorinine as a comparatively favorable predicted lead candidate (LD₅₀: 1000 mg/kg; Class 4 toxicity category). Pratorinine was identified as the most promising in silico antidiabetic candidate from the C. amoenum extract, primarily due to stable α-amylase interactions and favorable ADMET properties. Full article

Implantable neural probes that can simultaneously possess biocompatibility, electrochemical stability, and high signal fidelity are the core devices in neuroelectrophysiological research. In this article, AlGaN/GaN heterojunction field-effect transistors are used instead of traditional metal microelectrodes to prepare brain nerve probes. By photoelectrochemical etching and optimization of sensing area size, the probes have the maximum transconductance value, i.e., the highest sensitivity, under no gate control. After digital filtering processing, the neural probe achieved a signal-to-noise ratio of 8.04 dB on biological analog signals as low as 50 µV, confirming its ability to detect microvolt-level signals. The ex vivo recording of the bullfrog sciatic nerve further validated its biosensing performance, demonstrating the selective capture of composite action potentials from active neural tissue. Full article

Osteoarthritis (OA) causes irreversible cartilage damage, highlighting the need for early and sensitive assessment. Current imaging modalities are limited in detecting early-stage changes. Ultrasound (US) provides a non-invasive and accessible alternative, but its clinical adoption is limited by the lack of standardized protocols and reliable cartilage assessment. Simulations can be used to address these challenges by enabling system design, acquisition optimization and validation by providing ground truth when in vivo ground truth is unavailable. The aim of this study is to develop an in silico framework for realistic US imaging of healthy and OA cartilage by combining accurate acoustic wave modeling with a 2D microstructural cartilage phantom. The model was calibrated to healthy cartilage using first-order speckle statistics and extended to simulate degeneration through changes in structural and acoustic properties. As a proof-of-concept study, simulations were evaluated against limited ex vivo US data from healthy and OA cartilage and compared with literature data. The simulations reproduced key OA-related features and trends, including changes in reflection coefficient (R), integrated reflection coefficient (IRC), apparent integrated backscatter (AIB), and gray level distributions. These findings demonstrate the feasibility of using microstructure-based tissue phantoms to model healthy and OA cartilage. The framework provides a platform for systematic investigation of cartilage microstructure and US-derived features and may support future generation of synthetic datasets for data-driven and AI-based OA assessment. Full article

Background/Objectives: This study engineered and evaluated a targeted, folate-functionalized chitosan nanoparticle (CS-FA NP) delivery system to enhance the therapeutic efficacy of standard quercetin and Coriandrum sativum seed extract against breast cancer. Methods: Phytochemical profiling confirmed a 14% crude yield for the methanolic extract, with gas chromatography–mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) identifying quercetin as the principal bioactive agent. The synthesized CS-FA NPs exhibited a core size of 7–20 nm, an average hydrodynamic diameter of 150–160 nm, a stable zeta potential of −55 mV, and high encapsulation efficiencies (87.2% for quercetin and 80.5% for coriander). Kinetic assessments confirmed a biphasic, diffusion-controlled release matching Higuchi matrix kinetics. Anticancer activity was evaluated in vitro using MTT cytotoxicity, Annexin V-FITC/PI apoptosis analysis, RT-qPCR, and ex vivo rat aortic ring assays, followed by validation in a syngeneic 4T1 mammary tumor mouse model. Results: In vitro, folate-receptor-targeted quercetin nanoparticles (T4) demonstrated superior, selective cytotoxicity, particularly against triple-negative MDA-MB-231 cells, while sparing normal fibroblasts. Annexin V-FITC/PI apoptosis profiling and ex vivo aortic ring assays revealed profound, cell-line-dependent programmed cell death and up to 90% inhibition of microvessel sprout outgrowth. Mechanistically, RT-qPCR verified that nano-formulations induced complete transcriptional silencing of NANOG, MMP-1, VEGFA, TSPAN8, TWIST, EMMPRIN, and CDK1, alongside marked upregulation of P27^KIP1 and P21^CIP1. In vivo, these nano-formulations successfully improved tumor-associated pathological features, reduced aggressive tumor spindle-cell proliferation, and suppressed elevated serum CA15-3 and arginase biomarkers. Conclusions: Folate-functionalized chitosan nano-formulations significantly enhanced the anticancer efficacy of quercetin and Coriandrum sativum seed extract through improved targeted delivery, potent antiproliferative, anti-angiogenic, and pro-apoptotic activities, together with favorable modulation of multiple molecular pathways associated with breast cancer progression. These findings support their potential as promising targeted nanotherapeutic strategies for breast cancer treatment. Full article

Background: Despite extensive development of liposomal antibiotics, the structural determinants governing their stability, release, and biological activity remain poorly understood. This study investigated how the cholesterol content and drug-to-lipid ratio affect membrane organization and thereby determine the physicochemical and biological properties of linezolid-loaded liposomes. Methods: Nine liposomal formulations, varying in their cholesterol content (10–30 wt%) and drug-to-lipid ratios (1–5%), were prepared by thin-film hydration. Membrane organization was analyzed by ATR-FTIR spectroscopy and principal component analysis. Liposomes were further characterized by particle size, ζ-potential, encapsulation efficiency, storage stability, in vitro release in phosphate buffer with and without bovine serum albumin, antibacterial activity against B. subtilis, and antimycobacterial activity in an ex vivo PBMC-derived Mycobacterium tuberculosis granuloma model. Results: The cholesterol content and drug-to-lipid ratio markedly altered membrane interfacial organization, particularly the hydration of the carbonyl and phosphate regions. These structural changes correlated with differences in storage stability, protein-responsive release, and antibacterial activity. Functional behavior was non-monotonic, as 30-L showed the highest overall storage stability, while the apparent release depended jointly on the cholesterol content, drug loading, and medium. BSA altered the composition-dependent release pattern instead of producing a uniform effect. In the exploratory granuloma model, the formulations 10-S, 10-L, and 30-M reduced M. tuberculosis CFU by >99%, whereas free linezolid produced approximately 60% inhibition. Conclusions: Membrane interfacial organization is a key determinant of the functional performance of liposomal linezolid, establishing a structure–property–function relationship that provides a mechanistic basis for the rational design of liposomal antibiotic delivery systems for tuberculosis therapy. Full article

Background: This study evaluates transdermal delivery of tamoxifen (TXN) as an alternative to the oral route of administration in treating breast cancer, which is the leading cause of cancer-related death in women globally. Oral TXN, a Class II drug, is associated with first-pass metabolism and serious side effects, including secondary cancers. Objectives: To enhance transdermal delivery, lipid-based transethosomes (TRS) were formulated using three different 2⁴ factorial designs with various non-ionic surfactants, including Tween 20^®, Span 20^®, and Span 80^®. Methods: Optimized TRS formulations were incorporated into HPMC-based gels and characterized for morphology, drug content, pH, viscosity, spreadability, ex vivo skin penetration, and deposition. Additionally, cytotoxicity and stability were assessed. Results: All TXN-TRS gels were suitable for transdermal use; however, Span 20^®-based TRS gel demonstrated the highest skin penetration (40.3 ± 1.5 µg/cm²), representing a 127-fold enhancement rate compared with the non-ethosomal TXN gel. In line with the enhanced penetration profile, cellular studies on MCF-7 cells showed concentration-dependent cytotoxicity, reaching 91.24 ± 1.01% inhibition at 2% w/w after 72 h, with an IC₅₀ value of 0.85 ± 0.02% w/w. Stability testing showed all formulations were more stable under refrigeration than at dry room temperature storage, supporting their potential as preclinical transdermal tamoxifen delivery platforms. Conclusions: Span 20^®-based TXN transethosomal gel markedly enhanced skin penetration while maintaining potent cytotoxic activity, supporting its further preclinical evaluation as a promising transdermal alternative to oral tamoxifen. Full article

Cataracts are the leading cause of reversible blindness worldwide; this condition results from the aggregation of lens proteins. Currently, surgery remains the only treatment; however, there is growing interest in non-surgical approaches, including the use of bioactive compounds incorporated into nanostructured systems designed to enhance solubility, enable controlled release, and improve bioavailability and bioactivity. Among the bioactive compounds investigated, curcumin has attracted considerable attention due to its antioxidant and anti-inflammatory properties, positioning it as a potential anticataractogenic agent. In the present study, curcumin-loaded nanoemulsion was developed via ultrasonication and characterized by average particle size, D90 percentile, ζ potential, and rheological behavior. In addition, its anti-cataract efficacy was evaluated both using an in vivo model in rats and an ex vivo model employing human cataract samples. The resulting curcumin-loaded nanoemulsion exhibited an average particle size of 152 ± 19.79 nm with a monomodal distribution, along with good physical stability over time. The nanoemulsion exhibited apparent viscosity between 30 and 25 mPa·s, at shear rate values (100 to 0 s⁻¹), indicating slight shear-thinning behavior. Regarding the effect on cataracts, in the in vivo model, cataract reversal was observed. Furthermore, ex vivo isothermal titration calorimetry (ITC) analyses indicated exothermic heat exchange between the curcumin nanoemulsions and cataract fragments, consistent with binding interactions occurring within lens components, likely involving crystallin proteins. These findings provide biophysical and in vivo evidence that intravitreally administered curcumin-loaded nanoemulsions not only prevent but actively reverse lens opacity, positioning them as a promising non-surgical therapeutic approach for cataract treatment. Full article

Sensorineural hearing loss, caused by irreversible hair cell (HC) loss, remains incurable due to the inability of the mammalian cochlea to regenerate HCs spontaneously. Although the combinatorial modulation of Notch and Wnt signaling robustly reprograms cochlear supporting cells to HCs in vitro, these strategies show limited success in vivo, which suggests that the native cochlear microenvironment imposes inhibitory cues. Here, we identify hypoxia-inducible factor 1α (HIF1α) as a critical barrier to HC reprogramming in vivo. We found that HIF1α accumulates in the basilar membrane of the intact cochlea, whereas ex vivo culture rapidly eliminates this accumulation. Mimicking the in vivo hypoxic state recapitulated the reprogramming blockade, hindering supporting cells from completing the fate transition to HCs. Mechanistically, HIF1α selectively suppressed Wnt signaling, as evidenced by the reduced expression of Wnt target genes and Wnt10a. Importantly, the pharmacological inhibition of HIF1α rescued the impaired reprogramming under hypoxia. These findings demonstrate that HIF1α accumulation in the hypoxic cochlear environment antagonizes Wnt-mediated HC differentiation, providing a mechanistic explanation for the failure of in vivo regeneration. Targeting HIF1α to restore supporting cell reprogramming competence within the hypoxic cochlear niche represents a promising, clinically translatable strategy for functional HC regeneration and hearing restoration. Full article

Background/Objectives: This study evaluated the adaptation of a novel filling material, Odne^®Fill (ODNE, Dübendorf, Switzerland), to instrumented root canal walls using micro-computed tomography. Methods: Fourteen extracted human molars (six maxillary and eight mandibular), comprising a total of 32 root canals, were included in this study. Following preparation, all root canals were filled with Odne^®Fill according to the manufacturer’s instructions. The extent of the root canal area coverage by the novel filling material was assessed using both periapical radiographs and micro-CT. The filling material adaptation to the canal walls was quantified through image segmentation and statistically analyzed. Results: The percentage of canal wall coverage ranged from 93.31% to 99.98%. The mean coverage rate was 97.63% (standard deviation: 1.70%), with a median value of 98.23%, indicating a high degree of adaptation of the filling material to the ex vivo prepared canal walls. Conclusions: Within the limitations of this ex vivo study, Odne^®Fill demonstrated high adaptation values to the prepared root canal walls. These findings should be interpreted with caution. Further comparative studies and long-term investigations are required to determine the clinical significance and performance of the studied material under in vivo conditions. Full article

Real-time tissue identification during laser-guided surgery is a critical unmet need for collateral damage avoidance and margin delineation. Laser-Induced Breakdown Spectroscopy (LIBS) is compatible with pulsed laser surgical systems and offers rapid, label-free elemental analysis. This study presents a machine learning pipeline classifying five ex vivo bovine tissue classes, plus one synthetic null-signal control class, from LIBS spectra, designed to control specimen-level data leakage and class imbalance bias. Key contributions are (i) a ‘peak max over baseline’ aggregation strategy suppressing shot noise while preserving emission peaks; (ii) a repeated, group-based cross-validation protocol (GroupShuffleSplit, N = 10) enforcing specimen-level separation; and (iii) a comparison of 30 configurations (10 classifiers × 3 pipelines). Extra Trees with normalization reached the highest weighted F1-score (0.934 ± 0.118); excluding the synthetic control, five-class scores fall to 0.875–0.915 and the ranking changes, so these are the reference figures for biological tissue discrimination. Support Vector Machines were less accurate but more consistent (0.917 ± 0.069). Acquisition takes approximately 3 s per point; inference is sub-millisecond. With five source animals, the best configuration chosen on the same outer splits, and inner tuning that was not group-aware, these estimates are an exploratory step toward real-time guided surgery. Full article