Identification of novel candidate targets for suppressing ovarian cancer progression through IL-33/ST2 axis components using the system biology approach

Background: Cancer-associated fibroblasts (CAFs) of ovarian cancer (OvC) are the most prevalent element of the tumor microenvironment (TM). By promoting angiogenesis, immunological suppression, and invasion, CAFs speed up the growth of tumors by changing the extracellular matrix’s structure and composition and/or initiating the epithelial cells (EPT). IL-33/ST2 signaling has drawn a lot of attention since it acts as a pro-tumor alarmin and encourages spread by altering TM.Methods: Differentially expressed genes (DEGs) of the OvC tumor microenvironment were found in the GEO database, qRT-PCR, western blotting, and immunohistochemistry, and their presence and changes in healthy and tumor tissue content were examined. Primary cultures of healthy fibroblasts and CAFs obtained from healthy and tumor tissues retrieved from OvC samples were used for in vitro and in vivo investigations. Cultured primary human CAFs were utilized to investigate the regulation and the IL-33/ST2 axis role in the inflammation reactions.Results: Although ST2 and IL-33 expression was detected in both epithelial (EPT) and fibroblast cells of ovarian cancer, they are more abundant in CAFs. Lipopolysaccharides, serum amyloid A1, and IL-1β, the inflammatory mediators, could all induce IL-33 expression through NF-κB activation in human CAFs. In turn, via the ST2 receptor, IL-33 affected the production of IL-6, IL-1β, and PTGS2 in human CAFs via the MAPKs-NF-κB pathway.Conclusion: Our findings suggest that IL-33/ST2 is affected by the interaction of CAFs and epithelial cells inside the tumor microenvironment. Activation of this axis leads to increased expression of inflammatory factors in tumor CAFs and EPT cells. Therefore, targeting the IL-33/ST2 axis could have potential value in the prevention of OvC progression

Fabrication of magnetic niosomal platform for delivery of resveratrol: potential anticancer activity against human pancreatic cancer Capan-1 cell

Abstract Recently, the presence of different nanoparticles (NPs) has developed targeting drug delivery in treatment of cancer cell. Targeted drug delivery systems using NPs have shown great promise in improving the efficacy of intracellular uptake as well as local concentration of therapeutics with minimizing side effects. The current study planned to synthesized resveratrol-loaded magnetic niosomes nanoparticles (RSV-MNIONPs) and evaluate their cytotoxicity activity in pancreatic cancer cells. For this aim, magnetic nanoparticles (MNPs) were synthesized and loaded into niosomes (NIOs) by the thin film hydration technique and then characterized via DLS, FT-IR, TEM, SEM and VSM techniques. Moreover, the cytotoxic activity of the RSV-MNIONPs on the Capan-1 cells line was assessed by the MTT test. The distribution number of RSV-MNIONPs was gained about 80 nm and 95 nm with surface charge of − 14.0 mV by SEM and TEM analysis, respectively. RSV loading efficacy in NIOs was about 85%, and the drug releases pattern displayed a sustained discharge with a maximum amount about 35% and 40%, within 4 h in pH = 7.4 and pH = 5.8, respectively. The cytotoxicity of the RSV-MNIONPs in the presence of an external magnetic field is higher than that of the RSV, indicating enhanced cellular uptake in their encapsulated states. Furthermore, RSV loaded MNNPs were found to induce more cell cycle arrest at the G0/G1 checkpoint than free RSV. Compared with RSV-treated cells, the mRNA expression levels of BAX, Bcl2, FAS, P 53, Cyclin D and hTERT, were significantly changed in cells treated with RSV loaded MNNPs. The niosomes NPs approaches have been widely used to attain higher solubility, improved bioavailability, enhanced stability, and control delivery of RSV. Our formulation displayed antitumor activity and can be considered an appropriate carrier with a great potential for future usage in cancer therapy

Comparison of Levels of Nephropathy Biomarkers in HIV-infected Individuals and Healthy Volunteers

Introduction: The number of human immunodeficiency virus (HIV)-infected individuals (HIIs) is increasing day by day and life expectancy is prolonged with the use of highly active antiretroviral therapy (HAART). With the advancing age, chronic diseases that may cause renal dysfunction will also begin to appear. In addition, HIV-associated nephropathy due to inflammation caused by HIV itself and renal dysfunction due to HAART use have been reported in the literature. Considering the social and medical problems caused by HIV, nephropathy as an additional disease makes patient management difficult. Therefore, it is important to detect nephropathy in the early period and take precautions. Creatinine is not always sufficient in the evaluation of nephropathy. New searches are needed in demonstrating nephropathy in HIIs compared to healthy individuals. It was aimed to evaluate cystatin C and NGAL levels in serum, and KIM1 and NGAL levels in urine to determine whether nephropathy developed in HIIs. Materials and Methods: Eighty-eight HIIs in whom renal dysfunction was not detected before and 81 healthy individuals were prospectively evaluated. Cystatin C and NGAL levels were studied in serum samples, while KIM1 and NGAL were studied in urine samples. Serum creatinine, spot urine protein and creatinine levels were recorded in these patients. Results: Of all participants, 114 (67.5%) were male and 55 (32.5%) were female. It was observed that the estimated-glomerular filtration rate (eGFR) was higher, cystatin C level in serum, and NGAL level in serum and urine were higher in the control group than the patient group. Serum creatinine, urinary protein and urinary creatinine levels were higher in the HIV-infected patient group compared to the healthy control group (p<0.05). The estimated-glomerular filtration rate was lower in patients using tenofovir disoproxil fumarate (TDF) than in patients not using TDF (p=0.017). When all participants were evaluated, urinary NGAL level was higher in women (p<0.001). Conclusion: In our study, HIIs had higher creatinine levels and lower eGFR compared to the control group. In the control group, cystatin C in serum and NGAL in urine and serum were higher. These parameters did not correlate with creatinine level and creatinine-based eGFR in serum, which were standardized to assess renal function. Our study was a cross-sectional study and only one measurement was made. In our study, the NGAL level was found to be higher in women, especially in the urine, and it was necessary to pay attention to the gender factor when using nephropathy markers. Low eGFR was noteworthy in patients using TDF