Anti-Nociceptive Effect of Sufentanil Polymeric Dissolving Microneedle on Male Mice by Hot Plate Technique

Background: Despite the widespread use of opioids to manage severe pain, its systemic administration results in side effects. Among the subcutaneous and transdermal drug delivery systems developed to deal with adverse effects, microneedles have drawn attention due to their rapid action, high drug bioavailability, and improved permeability. Sufentanil (SUF) is an effective injectable opioid for treating severe pain. In this study, we investigated the analgesic effects of SUF using dissolvable microneedles. Methods: SUF polymeric dissolvable microneedles were constructed through the mold casting method and characterized by SEM and FTIR analysis. Its mechanical strength was also investigated using a texture analyzer. Fluorescence microscopy was applied in vitro to measure the penetration depth of microneedle arrays. Irritation and microchannel closure time, drug release profile, and hemocompatibility test were conducted for the validation of microneedle efficiency. Hot plate test was also used to investigate the analgesic effect of microneedle in an animal model. Results: Local administration of SUF via dissolving microneedles had an effective analgesic impact. One hour after administration, there was no significant difference between the subcutaneous and the microneedle groups, and the mechanical properties were within acceptable limits. Conclusion: Microneedling is an effective strategy in immediate pain relief compared to the traditional methods.</p

Photocatalytic Degradation of Acetaminophen by g-C3N4/CQD/Ag Nanocomposites from Aqueous Media

Ternary g-C3N4/CQD/Ag photocatalysts were synthesized via deposition of carbon quantum dots (CQDs) and silver nanoparticles (Ag) onto graphitic carbon nitride (g-C3N4) for efficient acetaminophen degradation. The nanocomposites exhibited enhanced photoresponse and broad-spectrum photocatalytic activity under both UV (254 nm, 250 W) and Xenon (&gt;420 nm, 500 W) irradiation. Characterization by XRD, FTIR, SEM, PL, and EDX elucidated the material&rsquo;s composition, structure, morphology, and optical properties. Optimized photocatalytic degradation of acetaminophen (50 mg/L) was achieved at pH 7 with 0.6 g/L catalyst loading and 60 min irradiation, yielding degradation efficiencies of 87.5% (UV) and 85.3% (Xenon). Radical quenching experiments and GC-MS analysis identified hydroxyl radicals as the primary reactive species and revealed a gradual decrease in intermediate toxicity during mineralization. This study demonstrates the superior photocatalytic performance of the ternary g-C3N4/CQD/Ag nanocomposites compared to binary systems for effective acetaminophen removal

Synthesis, biological activities, and molecular docking studies of triazolo[4,3-b]triazine derivatives as a novel class of ?-glucosidase and ?-amylase inhibitors

In diabetes mellitus, amylase and glucosidase enzymes are the primary triggers. The main function of these enzymes is to break macromolecules into simple sugar units, which directly affect blood sugar levels by increasing blood permeability. To overcome this metabolic effect, there is a need for a potent and effective inhibitor capable of suppressing the enzymatic conversion of sugar macromolecules into their smaller units. Herein, we reported the discovery of a series of substituted triazolo[4,3-b][1,2,4]triazine derivatives as alpha-glucosidase and alpha-amylase inhibitors. All target compounds demonstrated significant inhibitory activities against alpha-glucosidase and alpha-amylase enzymes compared with acarbose as the positive control. The most potent compound 10k, 2-[(6-phenyl-[1,2,4]triazolo[4,3-b][1,2,4]triazin-3-yl)thio]-N-[4-(trifluoromethyl)phenyl]acetamide, demonstrated IC50 values of 31.87 and 24.64 nM against alpha-glucosidase and alpha-amylase enzymes, respectively. To study their mechanism of action, kinetic studies were also done, which determined the mode of inhibition of both enzymes. Molecular docking was used to confirm the binding interactions of the most active compounds.National Institute for Medical Research Development [53816]; National Institute for Medical Research Development (NIMAD) [RGD-020]; Scientific Research Project Fund of Sivas Cumhuriyet University (CUBAP)This work was supported by a grant from the National Institute for Medical Research Development (NIMAD), grant no. 53816. The numerical calculations reported in this paper were fully/partially performed at TUBITAK ULAKBIM, High Performance and Grid Computing Center (TRUBA resources). This work was supported by the Scientific Research Project Fund of Sivas Cumhuriyet University (CUBAP) under the project number RGD-020

Meta-analysis of promoter methylation in eight tumor-suppressor genes and its association with the risk of thyroid cancer.

Promoter methylation in a number of tumor-suppressor genes (TSGs) can play crucial roles in the development of thyroid carcinogenesis. The focus of the current meta-analysis was to determine the impact of promoter methylation of eight selected candidate TSGs on thyroid cancer and to identify the most important molecules in this carcinogenesis pathway. A comprehensive search was performed using Pub Med, Scopus, and ISI Web of Knowledge databases, and eligible studies were included. The methodological quality of the included studies was evaluated according to the Newcastle Ottawa scale table and pooled odds ratios (ORs); 95% confidence intervals (CIs) were used to estimate the strength of the associations with Stata 12.0 software. Egger's and Begg's tests were applied to detect publication bias, in addition to the "Metatrim" method. A total of 55 articles were selected, and 135 genes with altered promoter methylation were found. Finally, we included eight TSGs that were found in more than four studies (RASSF1, TSHR, PTEN, SLC5A, DAPK, P16, RARβ2, and CDH1). The order of the pooled ORs for these eight TSGs from more to less significant was CDH1 (OR = 6.73), SLC5 (OR = 6.15), RASSF1 (OR = 4.16), PTEN (OR = 3.61), DAPK (OR = 3.51), P16 (OR = 3.31), TSHR (OR = 2.93), and RARβ2 (OR = 1.50). Analyses of publication bias and sensitivity confirmed that there was very little bias. Thus, our findings showed that CDH1 and SCL5A8 genes were associated with the risk of thyroid tumor genesis

Synthesis and activity evaluation of new benzofuran-1,3,4-oxadiazole hybrids against wood-degrading fungi

A series of novel benzofuran-1,3,4-oxadiazole hybrids were synthesized and evaluated as antifungal agents. The synthetic pathway was started from salicylaldehyde, which afforded 5-(substituted benzylthio)-1,3,4-oxadiazole derivatives in moderate to good yields. The compounds were investigated for their antifungal potential against white-rot, Trametes versicolor and brown-rot, Poria placenta and Coniophora puteana fungi at different concentrations (500, 1000 ppm). The obtaining results demonstrated that most of the compounds at 500 ppm concentration did not exhibit acceptable antifungal effects but they had better antifungal activity at 1000 ppm concentration. Compounds 5a, 5c, and 5i showed inhibition percentages of 14.6%, 23.0%, and 14.7%, against the growth of P. placenta and C. puteana, respectively. Among the compounds, the 2-(benzofuran-2-yl)-5-((2,6-difluorobenzyl)thio)-1,3,4-oxadiazole (5h) hybrid was the most active one.</jats:p