AML-derived extracellular vesicles negatively regulate stem cell pool size: A step toward bone marrow failure.

PURPOSE OF THE STUDY: Long-term repopulating hematopoietic stem cells (LTR-HSCs) have been previously shown to reside in close proximity to osteoblasts, where they take shelter in the bone marrow (BM) microenvironment against cytotoxic and apoptotic stimuli. Nevertheless, the function of the HSC niche is believed to undergo an adaptive evolutionary modification during leukemogenesis. Recent studies have demonstrated that leukemic clones can impact BM homing through extracellular vesicle (EV) secretion. However, the exact mechanism driving BM conversion is still unclear. In the present study, the human osteoblast cell line (MG-63) were subjected to various concentration of sera-derived EVs of patients with acute myeloid leukemia (AML) and healthy volunteers to assess if they are associated strongly enough to alter the expression pattern of cross-talk molecules involved in niche interactions. METHOD: To gain a brief insight into the EVs secretion criteria, we first conducted a comparative analysis of sera-derived EVs by dynamic light scattering (DLS), transmission electron microscopy (TEM), and Bradford assay. After incubating MG-63 cell lines with increasing concentrations of the EVs, Trypan-blue and microculture tetrazolium test (MTT) assays were used to evaluate the cell survival, logarithmic growth, and metabolic activity. Finally, the expression levels of OPN, ANGPT-1, and JAG-1 transcripts were evaluated through the qRT-PCR technique. RESULTS: Here, we report that AML-derived EVs can affect the viability, cell growth, and metabolic activity of the human osteoblasts cell line (MG-63) compared to those that received healthy-derived EVs. We also found that leukemic EVs tend to induce overexpression of OPN but reduce the expression of ANGPT-1 and JAG-1 genes in the osteoblast transcriptome, which may provide a potential context imposing selective suppression of HSC pool size. CONCLUSION: These findings extend the general concept of a novel mechanism in which leukemic EVs would make it possible to create a specialized pre-metastatic microenvironment in the interest of tumor expansion, allowing leukemic clones to overcome their HSCs counterparts.

The protective effect of oleuropein against radiation-induced cytotoxicity, apoptosis, and genetic damage in cultured human lymphocytes.

PURPOSE: The aim of this study was to evaluate the effects of oleuropein radiation protection and to find an effective radioprotector. MATERIALS AND METHOD: Human mononuclear cells were treated with oleuropein at the concentration of 100 µM (optimum concentration), incubated for 24 h, and then exposed to 2 Gy gamma-rays. The anti-radiation effect of oleuropein was assessed by MTT assay, flow cytometry, comet assay, and micronucleus (MN) assay. RESULTS: It was found that pretreatment with oleuropein (25, 50, 75, 100, 200, 400, and 800 nM, and 1, 5, 10, 15, 20, 25, 30, 40, 50, 75, 100, 125, 150, 175, and 200 µM) significantly increased the percentage of cell viability compared to the irradiated group (p < .001). Moreover, oleuropein treatment with the above concentrations defined without gamma-ray did not show any cytotoxicity effect in human mononuclear cells. The LD50/24h dose was calculated as 2.9 Gy, whereas by 200, 150, 50, and 100 µM oleuropein prior to radiation (1, 2,and 4 Gy), radiation LD50/24h increased to 3.36, 3.54, 3.81, and >4 Gy, in that order. A very noticeable dose-modifying factor (DMF) of 1.16, 1.23, 1.31, and 1.72 was observed for 200, 150, 50, and 100 µM, in order. Therefore, 100 µM of oleuropein was selected as the desirable dose for radio-protection trial, and 2 Gy gamma-rays were used for further research. Human mononuclear cells treatment with oleuropein (100 µM) prior to 2 Gy gamma-rays significantly decreased apoptosis, genomic damage, and MN occurrence in human mononuclear caused by gamma-radiation (p < .001). Furthermore, treatment with oleuropein (100 µM) without radiation did not lead to apoptosis, genotoxicity, or clastogenic effects caused by oleuropein in human mononuclear cells. CONCLUSION: The results revealed that oleuropein is able to significantly reduce cytotoxicity, apoptosis, genotoxic, and clastogenic effects of gamma-rays.

Effect of platelet-rich plasma on pregnancy outcomes in infertile women with recurrent implantation failure: a randomized controlled trial.

METHODS: This study was directed to assess the efficacy of autologous platelet-rich plasma (PRP) on pregnancy rate in recurrent implantation failure. Between 2016 and 2019, a total of 98 women who unsuccessful to be pregnant after three or more high-quality embryo transfers undergoing frozen-thawed embryo transfer with or without an intrauterine infusion of platelet-rich plasma. Thus, 0.5 ml of platelet-rich plasma at 4-6 times higher concentration than peripheral blood infused intrauterine 48 h before embryo transfer. A control group underwent standard protocol. RESULTS: There were no significant differences between the two groups in terms of age, body mass index and duration and cause of infertility and total transferred embryos and kind of treatment protocol, but secondary infertility and endometrial thickness 96 h before embryo transfer, was more in the intervention group. The clinical pregnancy (48.3% versus 23.26; p = .001) and ongoing pregnancy (46.7% versus 11.7%; p = .001) and implantation rate (58.3% versus 25%; p = .001) was more significant in the intervention group rather than controls. In conclusion, intrauterine infusion of platelet-rich plasma 48 h before freeze-thawed embryo transfer may have more effectiveness in in vitro fertilization (IVF) outcomes in recurrent implantation failure.

Triangle collaboration assessment of autophagy, ER stress and hypoxia in leukemogenesis: a bright perspective on the molecular recognition of B-ALL.

B-lineage acute lymphoblastic leukemia (B-ALL) is the most common acute leukemia in childhood and adults, which caused by many various crystalline and unclear agents. Owning to this matter, no significant progress has been made in the patients-recovery. Recently, autophagy pathway is considered as an ambiguous agent in leukemia evaluation. We aim to discover the expression levels of upstream autophagy-regulating genes in newly diagnosed B-ALL patients. In B-ALL group, BECN1, HIF1A and ERN1 expressions were significantly down-regulated, while BCL2 expression was up-regulated compared to the control group (p < .05). Moreover, there was significant positive correlation between the decreased BECN1 compared with Hypoxia and endoplasmic reticulum (ER) stress-related genes expression in the patients (p < .05). Our findings revealed that, ERN1 and ER stress pathway-related genes could be effective regulators of autophagy in B-ALL. More investigation is recommended to gain a deeper understanding into molecular pathophysiology of B-ALL to improve treatment and monitoring approaches in affected patients.

Standardization of Plasma Rich in Growth Factors (PRGF) and its effects on androgenic hair loss.

Androgenic alopecia (AGA), as the most common cause of hair loss, is a chronic process that affects 80% of men and 50% of women throughout life. Existing and approved treatments for this condition are limited, and unfortunately, the length of treatment is long, while its efficacy is not much suitable. Plasma rich in growth factors (PRGF) autologous therapy is based on the delivery of a pool of bioactive molecules impressive for the treatment of AGA.Thirteen patients were included in this study. Our patients were evaluated in two groups: the first group was injected once and the second group was injected thrice, then evaluated for the number and diameter of the hair.Both groups of patients showed hopeful results so that in the first group hairs number and thickness increased by 9-54% and 11-76% respectively (p < .01). For patients who underwent PRGF injection thrice, the increases in hairs number and thickness were remarkably higher with an average of 211 and 221 respectively (p < .001). No adverse effect was reported in any patient.Our results revealed that PRGF platelet concentration using a higher volume of blood compared to previous protocols has higher effectiveness in treating AGA. However, more randomized clinical studies with longer follow up courses as well as larger sample sizes are needed to standardize an optimum protocol for PRGF based treatments.