Metabolomic profiling of embryo culture media in patients with repeated implantation failure during assisted reproductive technology cycles.

Objective: This study investigated the metabolic status of the spent culture media from embryos of patients with repeated implantation failure (RIF) undergoing in vitro fertilization-intracytoplasmic sperm injection cycles in comparison with the embryos from healthy fertile women. Methods: Metabolite levels in spent culture media were assessed and compared between embryos from RIF patients (n=35) and oocyte donors as controls (n=15). Protein levels of insulin-like growth factor 1 (IGF-1) were determined using Western blotting. Concentrations of glucose, pyruvate, and lactate were measured using spectrophotometry. Ionic colorimetric assay kits were utilized to analyze the concentrations of sodium, chloride, calcium, and magnesium ions. High-performance liquid chromatography was employed to measure the concentrations of glutamic acid, aspartic acid, methionine, phenylalanine, and histidine. Results: Glucose consumption and lactate secretion were higher in the control group than in the RIF group. The magnesium concentration was significantly higher in the control group than in the RIF group, but glutamic acid and aspartic acid concentrations were lower in the control group than in the RIF patients (p<0.05). The levels of IGF-1, sodium, calcium, chloride, methionine, histidine, and phenylalanine did not show statistically significant differences between the two groups. Conclusion: The metabolic profile of the culture medium of the embryos in the RIF group differed from that of the control group. These findings suggest potential factors that may affect implantation capacity in RIF patients and provide a new perspective on embryo selection.

Static magnetic field reduces cisplatin resistance via increasing apoptosis pathways and genotoxicity in cancer cell lines.

Cisplatin is a chemotherapy drug widely used in cancer treatment. Alongside its clinical benefits, however, it may inflict intolerable toxicity and other adverse effects on healthy tissues. Due to the limitation of administering a high dose of cisplatin as well as cancer drug resistance, it is necessary to utilize new methods optimizing treatment modalities through both higher therapeutic efficacy and reduced administered doses of radiation and drugs. In this study, sensitive (A2780) and resistant (A2780CP) ovarian carcinoma cells underwent treatment with cisplatin + static magnetic field (SMF). First, the levels of genotoxicity after treatment were evaluated by Comet assay. Then, cell cycle analysis and apoptosis assay were conducted by a flow cytometer. Lastly, the expression levels of genes involved in apoptosis and cellular drug uptake were investigated by PCR. After treating different groups of cells for 24, 48, and 96 h, the co-treatment of SMF and cisplatin as a combination managed to increase the amount of DNA damage in both sensitive and resistant cell lines. A considerable increase in mortality of cells was also observed mostly in the form of apoptosis, which was caused by inhibition of the cell cycle. The combination also increased the expression levels of apoptotic genes, namely P53 and P21; however, it did not have much effect on the expression levels of BCL2. Besides, the levels of CTR1 gene expression increased significantly in the groups receiving the aforementioned combination. Our study suggests that the combination of cisplatin + SMF might have clinical potential which needs further investigations through future studies.

Evaluation of the effects of photodynamic therapy consisted of the blue laser and zinc oxide QDs on MDA-MB-231 cancer cells by inhibiting cancer markers and inducing apoptosis.

The increasing number of cancer patients has cast attention on developing new anti-cancer modalities. Photodynamic therapy is a safe anti-cancer approach, which encompasses (1) local administration of a photosensitizer and (2) light irradiation. Zinc oxide (ZnO) quantum dots (QDs) are photosensitizers that can be utilized for this purpose. In the present study, to better appreciate the likely more efficient cytotoxic effect of the combination of ZnO QDs and the visible 470-nm blue light in comparison to the QDs alone, several assays were to be conducted upon breast cancer MDA-MB 231 cells. MTT assay showed that in certain groups the combination displayed higher cytotoxic effects compared to those following QD treatment alone. LDH leakage and lipid peroxidation rates by the combination were significantly higher than treatment with either the blue laser or QDs. Although the combination managed to meaningfully reduce the number of colonies and CAT activity compared to QD treatment, there were no palpable differences between them. Lastly, the combination was able to increase the apoptotic genes, including BAX, TP53, caspase 3, and caspase 9 compared to QD, while, in the case of Bcl-2, an anti-apoptotic gene, none of the groups managed to make any tangible differences on its expression levels. Our findings propose that there may be synergistic effects between the blue laser and QD that can possibly be adopted in anti-cancer therapy in the future. However, further investigations regarding this matter are of the essence.

Silymarin-Loaded Tin(IV) Nanoparticles Exhibit Enhanced Bioavailability and Antiproliferative Effects on Colorectal Cancer Cells.

Silymarin (SM) exhibits potential therapeutic effects due to having antioxidant activity. However, the low solubility and bioavailability of SM restrict its biological performance. To overcome this limitation, this study aimed to develop a nanoformulation composed of SM and dimethyltindichloride and investigate the effect of SM-loaded Sn nanoparticles on cancer cell growth and survival. An SM-Sn complex was synthesized and then characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FTIR), EDS-MAP, dynamic light scattering (DLS), and ζ-potential analysis. After that, the SW480 colorectal cancer cell line was treated with different concentrations of SM and the SM-Sn complex. Cell viability was examined through the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, analyzing apoptosis, and live-dead assay. The lipid peroxidation rate was assessed through the measurement of thiobarbituric acid (TBA). Intracellular reactive oxygen species (ROS) level and cell population in the cell cycle were measured using a flow cytometry instrument. To evaluate the colonization ability of SW480 cells, a colony formation assay was performed. Gene expression analysis was also conducted using a real-time polymerase chain reaction (PCR) technique. The findings of this study revealed the effectiveness of the SM-Sn complex in decreasing SW480 cell viability by inducing cell death-associated mechanisms. We found that the SM-Sn complex increases intracellular ROS level and malondialdehyde (MDA) content. It was also revealed that the SM-Sn complex induces cell cycle arrest and the expression of apoptotic genes. In addition, the SM-Sn complex could effectively hinder SW480 cells from constituting colonies. We conclude that the use of tin(IV) as a scaffold for enhanced delivery of SM could be considered an efficient option for inhibiting cancer cell proliferation and survival.

Investigation into the Effect of Photodynamic Therapy and Cisplatin on the Cervical Cancer Cell Line (A2780).

Introduction: Cervical cancer is recognized as one of the major causes of mortality among elderly women. Although there are several different therapeutic worldwide guidelines, many researchers have focused on screening new methodologies and technologies to elevate the efficiency of cervical cancer treatment. The simultaneous use of photodynamic therapy (PDT) along with chemotherapy as cisplatin has achieved good aims in the treatment of cervical cancer. Methods: A2780 cells were treated with cisplatin, photodynamic progress (laser with methylene blue as a photosensitizer compound) and a combination of cisplatin and PDT. The lithic effect of the laser, methylene blue and their combination and the IC50 value of cisplatin were calculated for each group. The amount of malondialdehyde (MDA) as membrane lipid peroxidation product and released lactate dehydrogenase was measured in the medium. The toxicity of each agent was evaluated by the MTT technique. Results: The results show that a combination of PDT and chemotherapeutic agent cisplatin caused a twofold decrease in viable cervical cancer cells compared to each therapeutic progress. The combination of both laser therapy and cisplatin enhanced cancer cell membrane disruption by increased membrane lipid peroxidation and apoptotic enzyme activation by the elevation of lactate dehydrogenase activity. Conclusion: The results indicated that cisplatin combined with PDT had a greater therapeutic effect on A2780 as a cervical cancer cell line. Therefore, PDT in combination with chemotherapy enhances the effectiveness of chemotherapeutic agents by the disruption of the cancer cell membrane and switching the apoptosis progress with less adverse effects.