Intradermal methylene blue analgesic application in posthemorrhoidectomy pain management: a randomized controlled trial.

Introduction: Unbearable post-hemorrhoidectomy pain is a well-documented challenge, significantly impacting patient well-being and satisfaction after surgery, often influencing patients to decline in undergoing this procedure. It is widely recognized that methylene blue has an effect of reducing inflammation and pain by reduces the production of nitric oxide and inhibiting the action potentials production in nerves. This study aims to explore the potential benefits of postoperative regional administration of methylene blue in providing extended relief from post-hemorrhoidectomy pain. Methods: This study included 97 patients aged 18-75 undergoing hemorrhoidectomy for stage III or IV hemorrhoids. A double-blind, randomized controlled trial compared postoperative intradermal injections of 1% methylene blue to 0.5% Marcaine as the control group. Two-week follow-up assessed pain. Statistical analysis, adherence to ethical standards, and registration were conducted. Result: No significant differences were found in baseline demographics, surgical parameters, or complications between the Methylene Blue and control groups. Intervention group remained lower in mean pain score until the 12th day. Methylene blue group reported significantly lower postoperative pain scores from days 1 to 7, with no significant differences afterward. Conclusion: This ongoing randomized controlled trial reveals the potential analgesic benefits of intradermal injection 1% methylene blue. It demonstrates comparable efficacy in reducing post-hemorrhoidectomy pain, with negligible side effects and complications.

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.

G Protein-Coupled Receptor 75 (GPR75) As a Novel Molecule for Targeted Therapy of Cancer and Metabolic Syndrome.

In recent years, molecular targeted therapy has attracted more attention from researchers due to its high efficiency and fewer side effects. Researchers are attempting to find more specific ways to treat diseases. It has been found that there are different targets for the treatment of diseases such as cancer, obesity, and metabolic syndrome. It is important to find a potential target in order to lessen the side effects of current treatments. G Protein-coupled receptors (GPCRs) are a large family of transmembrane proteins that are expressed in many organs, leading to the activation of internal signal transduction cascades through the binding of different ligands, including neurotransmitters, peptides, and lipids. Due to the critical role of GPCRs in cells, it could be a potential target. G protein-coupled receptor 75 (GPR75) is a novel member of the GPCR family that has an important role in many diseases, such as obesity, cancer, and metabolic syndrome. Until now, three ligands have been detected for GPR75, including 20-HETE, CCL5, and RANTES. Recent studies suggest that 20-HETE, through GPR75, triggers signaling pathways including PI3K/Akt and RAS/MAPK, leading to a more aggressive phenotype in prostate cancer cells. Additionally, the PI3K/Akt and RAS/MAPK signaling pathways activate NF-κB, which is significant in various pathways of cancer development such as proliferation, migration, and apoptosis. The findings indicate that inhibiting GPR75 in humans leads to an increase in insulin sensitivity and glucose tolerance, as well as a reduction in body fat storage. According to these discoveries, GPR75 could be a potential target for drug treatment of diseases such as obesity, metabolic syndrome, and cancer. In this review, we aimed to discuss the therapeutic impact of GPR75 in cancer, metabolic syndrome, and obesity and underscore the possible pathways.