Current Protein and Peptide Science - Volume 26, Issue 7, 2025

Ex vivo preconditioning increases the therapeutic potential of mesenchymal stem cells (MSCs) in terms of antioxidant activity, growth factor production, homing, differentiation, and immunomodulation. Therefore, it is considered an effective strategy to be used before transplantation and therapeutic application of MSCs. Histone deacetylase inhibitor (HDACi), valproic acid (VPA), has been reported to induce hepatic differentiation in MSCs. Although individual studies have shown that preconditioning and epigenetic modification enhance the survival and differentiation of MSCs, the combined effects of these therapies have not been fully explored. This study aims to investigate the combined effect of hydrogen peroxide (H2O2) preconditioning and HDACi (valproic acid) on the differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) into hepatic-like cells.

MSCs were first preconditioned with H2O2 and then cultured with VPA. The migration and proliferation potential of the treated cells were evaluated using wound healing and colony- forming unit assays. Furthermore, the expression of hepatic genes (FOXA2, CK8, CK18, TAT) and proteins (AFP, ALB, TAT) was evaluated in all treated groups.

The combined therapy group exhibited enhanced cell migration and proliferation, as evidenced by wound healing and colony-forming unit assays. Additionally, the combined treatment group showed higher expression of FOXA2, CK8, and CK18 hepatic genes and TAT protein, suggesting an improved differentiation of stem cells into hepatocytes.

In conclusion, the combination of H2O2 and VPA emerges as an important factor in promoting hepatocyte differentiation. However, further studies are required to optimize this protocol for future therapeutics.

Glioblastoma is a common primary malignant intracranial tumor in adults associated with high disability and mortality. Despite the use of traditional surgical methods, postoperative radiotherapy, and targeted therapies, the median survival for glioma patients remains disappointingly brief. As a result, there is an urgent need to explore new targets and develop novel targeted drugs to potentially improve patient survival. Notably, CLIC1 expression is upregulated in tumors and correlated to tumor aggressiveness, metastasis, and poor prognosis. Nonetheless, its potential role in gliomas remains largely unclear.

This study aimed to investigate the bioinformatics characteristics and clinicopathological features of CLIC1, including WHO classification and OS.

Immunohistochemistry and western blot analysis were carried out to detect the expression of CLIC1 in glioma tissues. Moreover, CCK8, plate clone formation assay, and EdU proliferation assay were carried out for cell proliferation ability. Transwell and scratch assay were performed for cell invasion and migration. Western blotting was also conducted to verify the relationship between CLIC1 and EMT and ERK1/2 signaling pathway. The effect of the knockdown of CLIC1 on tumor growth capacity was assessed in an intracranial xenograft model.

CLIC1 was found to be associated with poor prognosis in glioma patients, and in vivo experiments demonstrated that CLIC1 promoted GBM cell proliferation, invasion, and migration. In addition, CLIC1 positively regulated ERK1/2 signaling to promote the EMT process in GBM cells. In vitro experiments showed that CLIC1 could affect intracranial tumor progression in mice.

In summary, these findings expand our knowledge of CLIC1, confirming its oncogenic role and laying the groundwork for future development of pharmacological agents targeting this gene.

Colorectal cancer (CRC) is one of the most common malignancies worldwide, and despite advances in treatment, there remains a critical need for novel therapeutic approaches. Recently, anti-microbial peptides (AMPs) have gained attention for their potential use in cancer therapy due to their selective cytotoxicity towards cancer cells.

This study aims to evaluate the anti-cancer potential of two computationally engineered anti-microbial peptides (EAMPs) in SW620, SW480, and HCT116 colon cancer cells and the normal colon epithelial cell line CCD 841, focusing on their effects on cell proliferation, apoptosis, and DNA damage.

Cell proliferation and survival were measured using the CellTiter-Glo Luminescence and clonogenic assays. DNA damage was assessed through the Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Flow cytometry was used to examine cell apoptosis, cell cycle distribution, and mitochondrial membrane potential in SW620 cells.

EAMPs inhibited CRC cell proliferation in a dose-dependent manner, with minimal toxicity observed in normal colon epithelial cells. In SW620 cells, EAMPs induced DNA damage, resulting in cell cycle arrest at the S/G2 phase, apoptosis, and a reduction in mitochondrial membrane potential. The proliferation results were confirmed in SW480 and HCT116 CRC cell lines.

Our findings revealed that EAMPs exhibited significant anti-cancer activity against CRC cells in vitro while sparing normal epithelial cells. These results suggest that EAMPs may offer a potential therapeutic approach for colorectal cancer and warrant further investigation.

Secreted Frizzled-Related Protein 2 (SFRP2) is considered to be the most potent modulator of the Wnt signaling. This pathway is involved in the pathogenesis of Polycystic Ovary Syndrome (PCOS). This research aimed to compare the levels of SFRP2 in PCOS [infertile and Recurrent Pregnancy Loss (RPL) patients] with the control group and determine the correlation of SFRP2 with inflammation and insulin resistance.

This case-control study was conducted on 108 POCS patients (53 infertile patients and 55 women with RPL) and 54 healthy controls. The levels of biochemical factors along with SFRP2, adiponectin, Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), free testosterone, and insulin, high-sensitivity C-Reactive Protein (hs-CRP) were measured following the manufacturer's instructions.

Both infertile and RPL groups presented notably higher levels of SFRP2 (49.32 ± 17.72 ng/ml and 55.89 ± 17.36 ng/ml, respectively) compared to the control group (30.21 ± 10.12 ng/ml, P<0.001 for both groups). In PCOS patients, a positive correlation was observed between SFRP2 and body mass index (BMI) (r = 0.42, P < 0.001), insulin (r = 0.19, P = 0.04), fasting blood glucose (FBG) (r = 0.24, P = 0.01), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (r = 0.21, P = 0.03), triglyceride (r = 0.25, P = 0.009), and hs-CRP (r = 0.21, P = 0.02). Furthermore, SFRP2 increased the risk of RPL (OR (95% CI) = 1.15 (1.10 -1.20), P < 0.001) and infertility (OR (95% CI) = 1.12 (1.07 -1.17), P < 0.001) in comparison with the controls.

Our findings suggested that SFRP2 may have a potential involvement in the development of PCOS and might be a promising target for diagnosis, but additional research is required to confirm this.