G protein-coupled receptor (GPCR) 87, is overexpressed in various cancer cells especially pancreatic cancer and plays a critical role in tumor cell survival. Nano-particles (NP) have become the essential vehicles for nucleotide internalization to the cell, due to the negative charge of nucleotides and their poor stability in blood circulation. In this study, the HEK293T cell linewas transfected with GPR87-plasmid after which the double-stranded RNA molecules targeting the GPR87 gene were prepared and purified. 1.1B4 cancer cell lines were used as model pancreatic cancer cells. Produced siRNA molecules were encapsulated in Poly(Lactic-Co-Glycolic Acid) (PLGA) nano-micelles using three different methods, two of which were according to literature with (siR-PLGA-S) or without (siR-PLGA-V) sonication. However, a new method was suggested to overcome problems such as poly-dispersity and large sizes of siR-PLGA-S and siR-PLGA-V. The new method consists of encapsulating siRNA using mild agitation to the pre-made PLGA NPs. The latter method provided mono-dispersed particles (siR-P-PLGA) with 92 nm size and desired Encapsulation Efficiency (EE%). siR-P-PLGA was able to silence the GPR-87 gene in a ratio of 83.9%, almost 41 times more effective than siR-PLGA-S and siR-PLGA-V in HEK 293T cells. siR-P-PLGA was able to show a mild cytotoxic effect on 1.1B4 pancreatic cancer cells within 48 hours.

MiRNA and mRNA expression profiling in rat brain following alcohol dependence and withdrawal

The extract from larval Lucilia sericata is used clinically to promote wound healing and tissue regeneration. However, its effect and underlying mechanisms on fibroblast cells, which are involved in the wound healing process, are still poorly understood. This study aimed to examine the effects of larval secretions on dermal fibroblast activity and gene expression and to evaluate the wound healing potential of their major components. Primary rat fibroblasts were cultured and treated with larval secretions. Following the treatment, the cells were used to extract RNA for gene profiling. In addition, migration to the injury site was studied with the scratch healing assay. Our results showed that larval secretion accelerated the migration of the fibroblasts compared to the control cells and that several mRNAs were differentially expressed during a period of 72 h incubation. Additionally, we analyzed the chemical composition of larval secretions and showed that fumaric acid, ferulic acid, and p-coumaric acid, which were selected and identified for their major components, enhanced the migration of the fibroblasts. Therefore, these results indicate that L. sericata larval secretions could modulate the mRNA expression of some wound healing-related genes of the fibroblasts and contain the effective components for wound healing.

Lung cancer remains a leading cause of cancer-related deaths, largely due to therapy resistance and toxicity. This study develops novel quinazolinone-thiazolidinedione (TZD) hybrids by combining two anticancer pharmacophores to achieve more selective and potent EGFR inhibitors. A total of 14 quinazolinone-TZD hybrids were synthesized and characterized. Their cytotoxicity was evaluated in A549 lung adenocarcinoma and BEAS-2B normal bronchial cells. EGFR binding was analyzed via molecular docking and MM-GBSA, with 500 ns molecular dynamics simulations supporting the stability of selected complexes. ADME predictions assessed drug-likeness and oral bioavailability. Several compounds showed selective cytotoxicity against A549 cells, with compound 9 (thiophen-2-ylmethyl substituent) emerging as the most active (IC₅₀ = 3.85 μM, SI = 36.0), outperforming gefitinib (IC₅₀ = 9.59 μM, SI = 1.9) and exhibiting higher selectivity than sorafenib (IC₅₀ = 3.24 μM, SI = 5.4). Computational analyses revealed key interactions with EGFR residues (Cys-797, Arg-841, Asn-842, and Phe-997), supported by stable molecular dynamics behavior and favorable ADME predictions. These findings indicate that the synthesized hybrids, particularly compound 9, represent promising leads for selective EGFR-targeted lung cancer therapy and support further optimization.