Advanced nano-therapeutic delivery of metformin: potential anti-cancer effect against human colon cancer cells through inhibition of GPR75 expression.

The high incidence rate coupled with significant mortality makes colorectal cancer one of the most prevalent and devastating cancers worldwide. Research is currently underway to explore new forms of treatment that could potentially maximize treatment outcomes while minimizing the side effects associated with conventional chemotherapy. Metformin, a natural biguanide drug, has anti-cancer properties that can inhibit the growth and proliferation of cancer cells. However, due to its short half-life and low bioavailability, the efficacy of Metf as an anti-cancer agent is limited. The purpose of this research is to assess the potency of PEGylated niosomes as a nano-delivery system for Metf, with the aim of increasing its anti-cancer effects on CaCo2 colorectal cancer cells through the effect on the expression of genes, including GPR75, hTERT, Bax, Bcl2, and Cyclin D1. Metf-loaded niosomal NPs (N-Metf) were synthesized using the thin-film hydration method and then characterized using SEM, FTIR, AFM, and DLS techniques. The release pattern of the drug from the nanoparticles (NPS) was determined using the dialysis membrane method. Furthermore, the cytotoxic effect of the metformin-loaded PEGylated niosome on the CaCo2 cell line was evaluated by the MTT test. Additionally, an apoptosis assay was conducted to assess the effect of free Metf and Metf-loaded NPS on the programmed death of the CaCo2 cells, and the impact on the cell cycle was studied through a cell cycle test. Finally, the expression levels of hTERT, Cyclin D1, BCL2, GPR75, and BAX genes were assessed in the presence of free Metf and Metf-loaded NPs by RT-PCR. Characterization experiments showed successful loading of metformin into PEGylated niosomes. The results of cytotoxicity evaluation showed that Metf-NPs had more cytotoxicity than free Metf in a dose-dependent manner. Furthermore, nuclear fragmentation and the percentage of apoptotic cells induced by Metf-NPs were significantly higher than those induced by free Metf. Additionally, Metf-NPs were found to induce more cell cycle arrest at the sub-G1 checkpoint than free Metf did. Compared with Metf-treated cells, the mRNA expression levels of GPR75, Cyclin D1, and hTERT were significantly changed in cells treated with Metf-NPs. Ultimately, it is hypothesized the nano-encapsulation of Metf into PEGylated niosomal NPs could be a worthwhile drug delivery system to enhance its effectiveness in treating colorectal cancer cells.

Nonsurgical Management of a Large Periapical Lesion: A Case Report.

This case report describes the non-surgical management of a large cyst-like periapical lesion in the mandible of a 16-year-old female with the chief complaint of periodic swelling and pus drainage from the mandibular anterior region gingivae with no history of pain and traumatic accident in this area. Both mandibular central incisors had extensive caries. Root canals of both mandibular central incisors were filled with calcium hydroxide. After 10 days, endodontic therapy was carried out on both teeth. Clinical and radiographic re-evaluations at 3 and 12 months revealed progressing bone healing. This case report shows that appropriate diagnosis in combination with root canal treatment as a conservative non-surgical approach can lead to complete healing of large lesions without invasive treatments.