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Optimized nano-bilosomes loaded ocular insert as a promising approach for boosting voriconazole ocular bioavailability: In-vitro, microbiological, and in-vivo assessments
No full textThe eye possesses numerous physiological barriers that significantly limit the absorption of administered drugs, as only \u3c 5 % get through. These barriers restrict drug bioavailability, often necessitating multiple dosing, which can lead to poor patient compliance. The study goal is to efficiently incorporate Voriconazole (VRC), a wide-spectrum antifungal candidate with a short half-life, into stable, biocompatible, non-irritating bile salt nanoparticles (Bilosomes, BLOs) to enhance its ocular delivery. Bilosomes were prepared by the ethanol injection method. Experimental (33) Box–Behnken Design (BBD) was employed; the amount of bile salt, cholesterol, and span-60 were chosen as independent variables, while entrapment efficiency (EE%), cumulative VRC release (Q8h), particle size (PS), zeta potential (ZP), and polydispersity index (PDI) were the dependent variables. The formula of optimization showed EE% (59.04 ± 1.88 %), cumulative release after 8 h (81.35 ± 0.69 %), PS (222.53 ± 2.04 nm), ZP (−72.53 ± 1.75 mV), and PDI (0.225 ± 0.03). It was chemically characterized using DSC and FTIR. Its spherical arrangement was confirmed using TEM. For ophthalmic application, the optimized formula was included in ocular inserts to extend ocular residence time while minimizing dosing frequency. The optimal VRC-loaded bilosomal ocular insert met the acceptable physicochemical criteria, was sterilized using UV radiation for conducting microbiological assay, in-vivo study, and pharmacokinetic analysis. For safety evaluation, an eye irritation study and histopathological examination were conducted. The results confirmed its effectiveness as evidenced by a significantly larger inhibition zone and 8.39-fold enhancement in VRC bioavailability compared to its suspension. These findings support the potential of bilosomes-loaded ocular insert as an effective ocular delivery of VRC
Novel Repurposing of Empagliflozin-Loaded Buccal Composite (Chitosan/Silk Fibroin/Poly(lactic acid)) Nanofibers for Alzheimer’s Disease Management via Modulation of Aβ–AGER–p-tau Pathway
No full textBackground/Objectives: Empagliflozin (EMPA) was repurposed for Alzheimer’s disease (AD) treatment via buccal delivery, exploiting novel nanofibers (NFs) integrating chitosan (Cs), silk fibroin (Fb), and poly(lactic acid) (PLA). Methods: EMPA-loaded Cs/Fb/PLA NFs were electrospun in different formulations to optimize the formulation parameters. The optimized formulation was then investigated for its enhanced in vivo effect. Results: Optimized nanofiber diameters ranged from 459 ± 173 to 668 ± 148 nm, possessing bead-free morphology confirmed by SEM and satisfactory mechanical properties. EMPA was successfully well-dispersed in the polymer matrix as evidenced by FTIR, XRD, and drug content. The optimized NFs displayed a hydrophilic surface (contact angle \u3c 90◦), and biphasic drug release with sustained EMPA liberation (84.98% over 24 h). In vivo, buccal EMPA-Cs/Fb/PLA NFs in an AlCl3-induced AD rat model significantly reduced brain-amyloid-β, phosphorylated tau, IL-1β, and AGER expression by 2.88-, 2.64-, 2.87-, and 2.50-fold, respectively, compared to positive controls, and improved locomotor activity (1.86-fold) and cognitive performance (T-maze) (4.17-fold). Compared to pure EMPA, the nanofiber formulation achieved further reductions in amyloid-β (1.78-fold), p-tau (1.42-fold), IL-1β (1.89-fold), and AGER (1.38-fold), with efficacy comparable to memantine. Histopathological examination revealed preservation of the hippocampal neuronal structure. Conclusions: The findings suggest EMPA-loaded Cs/Fb/PLA NFs as a promising non-invasive, sustained-release buccal delivery platform for AD therapy, offering multimodal neuroprotection through modulation of the Aβ–AGER–p-tau axis
Curcumin Targets miR-21-3p: Promising Therapeutic Strategy for Treatment of Benign Prostatic Hyperplasia
No full textBackground It is still unclear if curcumin’s therapeutic effect in benign prostatic hyperplasia (BPH) is linked to microRNA regulation. This study explored the potential role of miR-21-3p in curcumin-induced anti-inflammatory and antiproliferative effects in BPH. Methods and results Twenty-four male adult rats were grouped randomly into four groups: normal control group, BPH group, BPH group treated with curcumin and BPH group treated with finasteride as a reference drug. The BPH model was experimentally induced by s.c. injection of testosterone enanthate (3 mg/ Kg) five times a week for two weeks, curcumin and finasteride were given orally, parallel to testosterone injection. The results showed that curcumin-induced decrease in prostate index and prostate-specific antigen (PSA)-like protein expression were associated with downregulation of miR- 21-3p compared with the BPH untreated group. Immunohistochemical staining revealed increased SIRT1 expression and decreased NF-κB and TNF-α expression in the curcumin-treated group compared to the BPH untreated group. In addition, β-catenin protein expression, measured by Western blotting, as well as β-catenin-linked signaling proteins, LRP6 and c-Myc, were suppressed in the curcumin group. The results obtained with curcumin treatment were comparable to those with finasteride treatment. Our data were supported by histopathological findings. Conclusions The current study demonstrated that curcumin alleviated the inflammatory manifestations of BPH by targeting the pro-inflammatory microRNA miR-21-3p, thereby upregulating SIRT1 and downregulating the pro-inflammatory mediators NF-κB and TNF-α. Furthermore, the anti-proliferative effect of curcumin may be attributed to the inhibition of the β-catenin signaling pathway
Interface-engineered N-CQD/g-C₃N₄ Heterostructures with tunable opto-elctronic features and enhanced thermal conductivity
No full textThe heterostructures of nitrogen doped carbon quantum dots (N-CQDs) with graphitic carbon nitride (g-C3N4) were fabricated using hydrothermal approach. Physicochemical characterizations, including FTIR, XRD, XPS, and HR-TEM were used to explore the phase structure, chemical composition and morphological structure of the heterostructures. The optical characteristics were investigated via using UV–vis spectrophotometry. The results confirm the strong coupling and compounding between N-CQDs and g-C3N4 to form a 0D/2D heterojunction. Furthermore, using the Tauc equation, the optical bandgap energy for g-C3N4 was dropped from 2.805 eV after conjugation with N-CQDs, reaching 2.797 eV, 2.76, and 2.795 as the concentration of N-CQDs in the heterostructure increased. Meanwhile, the PL of heterostructures is gradually blue shifted. However, upon increasing the amount of N-CQDs in the heterostructure, the extinction coefficient, refractive index, electronegativity, and optical conductivity enhanced. It is shown that Skin depth (δ) decreases as photon energy increases up to cut off wavelength λcutoff ∼ 3.8 eV, then increases exponentially with N-CQDs content in surface g-C3N4 sheets. Photoacoustic spectroscopy technique (PA) was used to evaluate the thermal diffusivity (α), thermal effusivity (e) and thermal conductivity (k) of prepared materials. The results show the values of (k) of g-C3N4 reached to 300 % increase upon conjugation with N-CQDs. Additionally, the thermal conductivity increased from 0.126 w m−1k−1to 0.596 w m−1 k−1, and the e values increased from 40 to 63.4 ws1/2m−2k−1 as the concentration of N-CQDs increase in the heterostructures. Finally, these results demonstrate the potential of N-CQDs/g-C₃N₄ heterostructures for multifunctional optoelectronic and thermal applications
Autophagy-Related Genes and Encoded Proteins’ Prognostic Significance in Various Cancer Types: A Molecular Perspective
No full textAutophagy is a degradative process for recycling and breaking down cellular components, with several context dependent functions in the development of tumors and resistance to therapy. Numerous clinical trials aiming to target autophagy in different tumors have been initiated as indicated by encouraging results from diverse preclinical investigations. Research on the connection between autophagosomes and the prognosis of different malignancies is now underway. The autophagy machinery itself may serve as a source of biomarkers for this purpose. Numerous research studies have established the association between autophagy-related genes (ATGs) and proteins (Atgs) in diverse types of cancer. Nonetheless, the outcomes of this association are still uncertain and the validation of reliable autophagy-related biomarkers is still lagging behind, owing to the paradoxical roles of autophagy in tumor biology and the scarcity of primary research studies. Herein, we explore recent developments, issues, and trends in the evaluation of clinically significant ATGs’ and their encoded proteins’ biomarker potential in human malignancies
Identification of LncRNA ZNF252P-AS1 as a Novel Diagnostic and Prognostic Biomarker for Breast Cancer Patients: An Integrated Bioinformatics and Experimental Analysis.
No full textLong non-coding RNAs (lncRNAs) have emerged as useful diagnostic and prognostic markers as well as therapeutic targets in cancer. Dysregulated levels of lncRNAs have been described in various cancers including breast cancer (BC). Our study aims to screen novel lncRNAs involved in BC and investigate any possible role in helping diagnosis and determining prognosis of BC patients. Methods: Bioinformatic tools were used to explore lncRNA expression profiles using publicly available datasets of BC and to predict any potential involvement in a competing endogenous RNA (ceRNA) network. A total of 100 serum samples of BC patients and healthy controls were collected to measure and experimentally validate expression level of the chosen novel lncRNA using RTqPCR. Results: The bioinformatic study identified a novel BC-related lncRNA called ZNF252P antisense RNA 1 (ZNF252P-AS1), which was one of the upregulated lncRNAs in our study, and its function in BC has not been investigated yet. LncRNA ZNF252P-AS1 was found to be overexpressed in BC patients relative to controls (p \u3c 0.01). Analysis of Kaplan-Meier curve showed that high ZNF252P-AS1 expression was correlated with shorter rates of overall survival, disease/relapse-free survival, and distant metastasis-free survival in BC patients with different subtypes. Furthermore, receiver-operating characteristic curve analysis demonstrated the potential ability of serum ZNF252P-AS1 to discriminate BC patients from healthy controls (AUC: 0.852, p = 0.000). We also found that lncRNA ZNF252P-AS1 had a significant positive correlation with TNM stage, tumor size, and distant metastasis of BC. To explore its regulatory role, a ceRNA network centered on ZNF252P-AS1 was constructed, identifying 14 interacting miRNAs and their 5983 mRNA targets. Conclusions: Our study is the first to address the abnormal level of lncRNA ZNF252P-AS1 in BC. Our findings highlight its potential as a non-invasive diagnostic and prognostic biomarker, and suggest a possible mechanistic role in BC pathogenesis through a lncRNA–miRNA–mRNA regulatory network
A study on Cu-doped V2O5: Investigating photocatalytic potential for environmental remediation
No full textThis study focuses on the photocatalytic performance of copper-doped vanadium pentoxide (Cu@V2O5) synthesized via a hydrothermal method for environmental remediation. Structural and morphological characterizations confirmed successful Cu incorporation without secondary phases, resulting in quasi-spherical nanoparticles with a narrowed band gap of 2.33 eV. The adsorption followed by photocatalytic activity was evaluated using methylene blue (MB) degradation under visible-light irradiation at a high initial dye concentration (100 ppm). Cu@V2O5 achieved 74% MB removal, with a pseudo-first-order rate constant of 0.0018 min−1. The material also exhibited moderate colloidal stability and strong surface interaction with cationic dyes. These findings highlight the role of Cu doping in enhancing visible-light activity and surface properties of V2O5, making Cu@V2O5 a promising candidate for wastewater treatment applications
New RPC gas mixtures for sustainable operation in the CMS experiment
No full textThe current operation of the Resistive Plate Chamber (RPC) system within the CMS experiment involves approximately 95% tetrafluoroethane (C2H2F4, TFE). However, in response to climate change concerns, the European Union has instituted a ban on TFE owing to its elevated Global Warming Potential, resulting in an associated increase in market prices. In this framework, shared endeavors within the RPC EcoGas@GIF++ Collaboration, have been dedicated to investigating novel ecological gaseous mixtures based on tetrafluoropropene (C3H2F4, HFO-1234ze) to ensure the sustainable functionality of RPCs. This contribution will delve into the performance outcomes derived from improved RPC gas gaps operating on HFO/CO2-based mixtures as ecologically viable alternatives, particularly in anticipation of the High Luminosity LHC phase (HL-LHC)
Adapt VR in dental education: boosting preclinical skill and self-confidence
No full textINTRODUCTION: Preclinical dental training requires extensive feedback and repetition, which traditional manikin exercises often lack. Adapt VR is a cost-effective, immersive system that delivers interactive, adaptive training with real-time feedback.
METHODS: This comparative study aimed to evaluate the effectiveness of the Adapt VR system in preclinical training. A total of 126 third-year dental students were randomly assigned to an Adapt VR Group 1 (n = 63), acquiring VR learning experience before practicing on laboratory simulators, or a control group (n = 63) who started their training on simulators directly. After practising Class I and II cavitypreparations, laboratory performance was scored with a standard rubric; VR participants also completed a post-training questionnaire.
RESULTS: The VR group achieved a higher mean laboratory score (6.31) than controls (3.93; p \u3c 0.001). Within the VR cohort no significant difference emerged between Class I and II scores (p = 0.16). Simulator averages were 81.5 for Class I and 79.4 for Class II. Most VR trainees reported increased confidence and an enhanced learning experience.
CONCLUSIONS: Iintegrating the Adapt VR system into preclinical dental education significantly enhances students’ skill acquisition and self-confidence compared to conventional manikin-based training