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Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease leading to neuronal cell death and manifested by cognitive disorders and behavioral impairment. Mesenchymal stem cells (MSCs) are one of the most promising candidates to stimulate neuroregeneration and prevent disease progression. Optimization of MSC culturing protocols is a key strategy to increase the therapeutic potential of the secretome. Objectives: Here, we investigated the effect of brain homogenate of a rat model of AD (BH-AD) on the enhancement of protein secretion in the secretome of periodontal ligament stem cells (PDLSCs) when cultured in a 3D environment. Moreover, the effect of this modified secretome was examined on neural cells to study the impact of the conditioned medium (CM) on stimulation of regeneration or immunomodulation in AD. Methods: PDLSCs were isolated and characterized. Then, the spheroids of PDLSCs were generated in a modified 3D culture plate. PDLSCs-derived CM was prepared in the presence of BH-AD (PDLSCs-HCM) and the absence of it (PDLSCs-CM). The viability of C6 glioma cells was assessed after exposure to different concentrations of both CMs. Then, a proteomic analysis was performed on the CMs. Results: Differentiation into adipocytes and high expression of MSCs markers verified the precise isolation of PDLSCs. The PDLSC spheroids were formed after 7 days of 3D culturing, and their viability was confirmed. The effect of CMs on C6 glioma cell viability showed that both CMs at low concentrations (> 20 mg/mL) had no cytotoxic effect on C6 neural cells. The results showed that PDLSCs-HCM contains higher concentrations of proteins compared to PDLSCs-CM, including Src-homology 2 domain (SH2)-containing PTPs (SHP-1) and muscle glycogen phosphorylase (PYGM) proteins. SHP-1 has a role in nerve regeneration, and PYGM is involved in glycogen metabolism. Conclusions: The modified secretome derived from 3D cultured spheroids of PDLSCs treated by BH-AD as a reservoir of regenerating neural factors can serve as a potential source for AD treatment.

Surgery is the standard treatment for breast malignancies, although local and distant relapses might occur. Previous studies have shown that surgery-induced wound fluid (WF) contains tumor-initiating and progressing factors; however, these experiments have only been performed on breast cancer cell lines. Since a cancerous tumor includes various components like malignant cells, recruited non-malignant cells and extracellular matrix, those investigations that only focused on cancer cell lines themselves are not adequate to establish WF's effects. We conducted a 3D model study where we mimicked the tumor microenvironment to re-assess previous in-vitro findings. We generated human-derived breast tumor spheroids from 23 patient specimens, dissociated and cultured them in microfluidic devices. The spheroids from each sample were treated with the patients’ WF or RPMI medium. The proportion of live and dead cells was assessed using live/dead assays and fluorescent imaging on day 6. In 22 samples, the percentage of live cells was significantly higher in the WF-treated group than in the RPMI-treated group. In one sample, we observed an opposite trend. The results were contrary in one of the samples, and we reported that case with more details. We compared the two groups using the 3D culture environment of human-derived tumor spheroids prepared from different microfluidic devices to mimic the tumor environment heterogeneity. Our findings showed that most patients with breast cancer benefit from surgical wound healing. However, removal of the surgical-induced serum may not be a method of inhibiting the tumor in all patients.

Background: Ovarian cancer (OC) has been reported as one of the three most prevalent malignant tumors in women. It has an onset of a difficult early diagnosis. The early detection of diseases has a vital role in survival rate of patients; the ovarian malignant tumor is no exception. The currently used tumor markers for differentiating low and high-risk levels of this disease are cancer (carbohydrate) antigen 125 (CA 125) as well as the risk of ovarian malignancy algorithm (ROMA). Carcinoembryonic antigen (CEA) is fetal glycoprotein synthesized in fetal tissues and in some carcinomas. Objectives: In this study, we investigated ROMA, CA-125, and CEA to evaluate the efficacy of these markers as predictors of peritoneal dissemination in early diagnosis of low-grade serous ovarian cancer. Methods: In this experimental study, CA-125, CEA, ROMA were determined in 10 patients with early-stage serous ovarian cancer and in 10 patients with benign tumors. Values and a cut-off level of CA-125, CEA, and ROMA were defined as positive when the values were as expected for ovarian cancer (CA-125 > 35 U/mL, CEA < 5 ng/mL and 25.3 for ROMA). The data were analyzed, using SPSS software (version 19). P < 0.01 was considered significant. Results: In our patients, the serum level of CA-125, CEA, and ROMA was higher in patients who were at their early stage of serous ovarian cancer than those with benign tumors. Conclusions: In this study, the difference between CA-125, ROMA, CEA levels in healthy and malignant cancerous patients was statistically significant, which is encouraging. The finding indicates that combined results of serum CA125, ROMA, and CEA can be considered as a promising biomarker for early stage detection of serous ovarian cancer.

Background: Our previous study determined the alteration in behavioral test-related memory and movement in male rats exposed to extremely low frequency electromagnetic field (ELF-EMF). The molecular mechanism of the effect of ELF-EMF on brain damage of rat has not yet fully understood, thus the current study investigated the effect of ELF-EMFs on hippocampus of male rats by the proteomics approach. The aim of this study was to investigate the effects of 50 Hz ELF-EMF at 0.5 and 1 mT 50 Hz for 2 and 4 weeks on male rats and determined protein expression of the hippocampus. Methods: Effects of 0.5 and 1 mT exposures for 2 and 4 weeks on protein expression was determined via proteomics techniques. Statistical analysis of proteome was performed using the Progensis Same Spots software. Bioinformatics analysis based on network was used for determining the mechanism. Results: Two-DE electrophoresis gels determined the effect of ELF-EMF on rat hippocampus, indicating that protein expression was overall down-regulated by increasing ELF-EMF intensity and time. The detected differentially expressed proteins between the groups comprised of Sptan1, Dpysl2, Tpi1, Lap3, Vdac1, and Tppp. Almost all were cytoskeletal proteins, most of which were increased by intensity and time. These proteins attributed to impairment in short memory of hippocampus after exposure to ELF-EMF. The GO analysis based on network, enriched two important biological process, cytoskeletal neurons and metabolic process. Conclusions: This study determined the effect of ELF-EMF, which led to change in protein expression related to the cytoskeleton that contributes to major processes in brain damage.