Combinatorial Chemistry & High Throughput Screening - Online First

In this research, 3-(triethoxysilyl)propyl isocyanate (TESPIC) functionalized chitosan was successfully synthesized to fabricate silica-coated magnetite nanoparticles (Fe3O4@SiO2-CS MNPs).

The synthesized MNPs were characterized using XRD, FT-IR, SEM, and TEM instruments and were utilized for the decolorization of Crystal Violet cationic dye (CV). The affecting variables controlling CV removal efficiency were investigated using the Taguchi fractional factorial design method (L16 array).

Under the optimized removal conditions (adsorbent amount = 0.12 g (4.8 g L^-1), pH = 4, ionic strength = 0.05 mol L^-1 NaCl, and 30 min stirring), 98.2% of the CV dye was eliminated. The kinetic and equilibrium adsorption isotherms were explained by the pseudo-second-order kinetic (R² = 0.999) and Freundlich isotherm models, respectively. MATLAB’s fmincon function as an efficient solution was applied in order to compare the Redlich-Peterson three-parametric isotherm model with two-parametric models. Moreover, the Fe3O4@SiO2-CS-TESPIC MNPs showed recyclability and reusability for subsequent runs.

The findings confirmed that these functional MNPs can be considered as proper adsorbents for the removal of CV dye from the aqueous solutions.

This study aimed to initially clarify the potential mechanism of quercetin in the treatment of non-small cell lung cancer (NSCLC) based on network pharmacology, molecular docking and in vitro experiments.

TCMSP, SwissTargetPrediction, TCMIP, STITCH, and ETCM databases were applied to obtain the targets of quercetin. NSCLC-related targets were retrieved from GeneCards, OMIM, PharmGKB, TTD, and NCBI databases. Their intersection targets were imported into the STRING database to construct a protein-protein interaction (PPI) network and core targets were identified through the Cytoscape 3.10.0 soft and the CytoHubba tool. Furthermore, Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the intersection targets. A compound-targets-pathways network was subsequently constructed to screen for key targets and pathways. Molecular docking was performed with Discovery Studio software to verify the interactions between quercetin and core targets. In vitro validations were conducted employing CCK-8 assays, flow cytometry, and Western blotting (WB).

193 potential targets of quercetin for treating NSCLC were obtained. The top ten core targets identified within the PPI network included TP53, HSP90AA1, AKT1, JUN, SRC, EGFR, ACTB, TNF, MAPK1, and VEGFA. GO analysis yielded 2319 items, and KEGG analysis resulted in 211 enriched pathways. Molecular docking results demonstrated a high affinity of quercetin towards the core targets. Based on the compound-targets-pathways network and molecular docking, the PI3K/AKT/P53 pathway and its key-related proteins (PIK3R1, AKT1, and TP53) were selected for further validation. Quercetin(20 and 40 μg/mL) significantly decreased the viability of A549 NSCLC cells but not BEAS-2B normal cells via CCK-8 assays. Flow cytometry and WB analyses further corroborated that quercetin could promote apoptosis of A549 cells by downregulating and upregulating the expression of Bcl-2 and Bax (P<0.05), respectively. Notably, quercetin did not significantly alter the total protein levels of PI3K, AKT, and P53 but downregulated the phosphorylation levels of PI3K and AKT (P<0.05) and upregulated the phosphorylation level of P53 (P<0.05).

Quercetin exhibits therapeutic potential in NSCLC by regulating the PI3K/AKT/P53 pathway to promote cell apoptosis.

To study the mechanism by which curcumin regulates ovarian primordial follicle initiation in rats with triptolide-induced diminished ovarian reserve (DOR).

An in vitro gelatin sponge culture was performed on 3-day-old rat ovaries. After the establishment of the DOR model with triptolide, curcumin was administered for 3 days. Histological analysis and follicle counts were performed using H&E staining. ELISA detection of ovarian hormones in the culture medium (E2, FSH and LH), western blotting and Q-PCR for protein and mRNA expression (LTCONS-00011173, TGF-β1, Smad1, AMH, PTEN and GDF-9).

Ovarian primordial and growing follicles increased significantly after curcumin intervention (p < 0.05), FSH/LH and E2 levels were increased significantly (p < 0.05). Curcumin also significantly decreased the expression of LTCONS-00011173. Meanwhile, curcumin increased the expression of TGF-β, AMH, and GDF-9 (p < 0.05). In addition, curcumin increased Smad1 gene expression and protein phosphorylation in the ovary on the one hand (p < 0.05), but inhibited Smad1 and p-Smad1 protein expression on the other hand (p < 0.05). Moreover, curcumin decreased PTEN protein and mRNA expression (p < 0.05).

Curcumin activates primordial follicles in DOR model rats through TGF-β1 and downstream AMH signaling pathways and may limit follicle exhaustion through LncRNA.

In this research, multicomponent reactions of cefixime, isothiocyanates, and alkyl bromides were carried out for the synthesis of new iminothiazole derivatives with high yields in water as the solvent at room temperature in the presence of catalytic amounts of Cu@KF/CP NPs as catalysts. Also, the ability of Cu@KF/Clinoptilolite nanoparticles (NPs) to adsorb and remove 4-NP and cefixime from water was investigated. The Cu@KF/Clinoptilolite nanoparticles were synthesized by employing a water extract of Petasites hybridus rhizomes.

For this experiment, all of the components obtained from Fluka and Merck were subjected to further purification. The antibiotic used in this investigation, cefixime, was obtained from a pharmaceutical facility situated in Sari, Mazandaran, Iran. The antibiotic factory is located in Sari City, Iran. All solutions were prepared using distilled water. The shape of Cu@KF/CP nanoparticles was analyzed using images obtained from a Holland Philips XL30 scanning electron microscope. An analysis was performed on the crystalline structure of Cu@KF/CP nanoparticles (NPs), and a room temperature X-ray diffraction (XRD) examination was carried out utilizing a Holland Philips Xpert X-ray powder diffractometer. The X-ray diffraction (XRD) examination was conducted using CuK radiation, which has a wavelength of 0.15406 nm. The analysis covered a 2ε angle range from 20 to 80°. The nanostructures that were produced were chemically analyzed using X-ray energy dispersive spectroscopy (EDS) with an S3700N equipment. The morphology and dimensions of Cu@KF/CP nanoparticles were characterized using a Philips EM208 transmission electron microscope operated at an acceleration voltage of 90 kV.

The primary objective of this study was to develop a sustainable approach for producing new iminothiazole derivatives 4. This was achieved using a highly efficient three-component reaction combining cefixime 1, isothiocyanates 2, and alkyl bromides 3. The reaction was carried out in water at ambient temperature, using Cu@KF/CP NPs as a highly effective catalyst, leading to excellent yields. Moreover, the study findings showed that the synthesized compounds demonstrated a significant antioxidant activity compared to conventional antioxidants. The antibacterial efficacy of the synthesized compounds was evaluated against both Gram-positive and Gram-negative bacteria. Furthermore, Cu@KF/CP nanoparticles were utilized to adsorb CFX and 4-NP from water-based solutions.

This study showcases the effective synthesis of innovative iminothiazole derivatives through the use of multicomponent reactions, involving the combination of cefixime, isothiocyanates, and alkyl bromides. The reactions were conducted in a water-based solvent. The reactions were carried out at room temperature, utilizing Cu@KF/CP NPs as catalysts. The Cu@KF/CP nanoparticles, a newly developed heterogeneous nanocatalyst, were synthesized and evaluated utilizing X-ray diffraction (XRD), field-emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDX), and transmission electron microscopy (TEM) research techniques. Cu@KF/CP nanoparticles are utilized to adsorb CFX and 4-NP from water-based solutions. The objects were manufactured using a straightforward and uncomplicated approach. The BET surface area of Cu@KF/CP NPs was measured to be 201.8 m²/g. The experimental equilibrium data was evaluated by applying the isotherms of the Langmuir, Freundlich, Dubinin-Radushkevich, and Redlich-Peterson models. Additionally, we examined the catalytic efficiency of Cu@KF/CP nanoparticles (NPs) in reducing various colors in water.

Ovarian Cancer (OC) is a lethal malignant tumor with a poor prognosis. Disulfidptosis is a newly identified form of cell death caused by disulfide stress. Targeting disulfidptosis is a new metabolic therapeutic strategy in cancer treatment. We aimed to establish a disulfidptosis-related lncRNA signature for prognosis prediction and explore its treatment values in OC patients.

Data from the TCGA and GTEx databases and a disulfidptosis gene set were used to establish a disulfidptosis-related lncRNA signature for prognosis prediction in OC patients. Then, we internally and externally (PCR) validated our model. We also built a nomogram to improve our model's predictive power. Afterward, GSEA was employed to explore our model's potential functions. The ESTIMATE, CIBERSORT, TIMER, and ssGSEA were applied to estimate the immune landscape. Finally, the drug sensitivity of certain drugs for OC patients was analyzed.

We built a prognosis model based on seven drlncRNAs, including AL157871.2, HCP5, AC027348.1, AL109615.3, AL928654.1, LINC02585, and AC011445.1. Our model performed well by internal validation. PCR data also confirmed the same trend in the lncRNA levels. Furthermore, the nomogram-integrated age, grade, stage, and risk score could accurately predict the survival outcomes of OC patients. Subsequently, GSEA unveiled that our model genes enriched the Hedgehog signaling pathway, a key regulator in OC tumorigenesis. Our predictive signature was associated with immune checkpoints, such as PD-1(P < 0.01), PD-L1(P < 0.001), and CTLA4 (P < 0.01), which might help screen out OC patients who are sensitive to immunotherapy. Small molecule drugs, such as AZD-2281, GDC-0449, imatinib, and nilotinib, might benefit OC patients with different risk scores.

Our disulfidptosis-related lncRNA signature comprised of AL157871.2, HCP5, AC027348.1, AL109615.3, AL928654.1, LINC02585, and AC011445.1 could serve as a prognostic biomarker and guidance to therapy response for OC patients.