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The nonspecific nature of cancer drug delivery often results in substantial toxic side effects during treatments for breast cancer. To mitigate these negative outcomes, our approach involves loading methotrexate (MTX) within carbon quantum dots (CQDs) synthesized from folic acid, which are then enveloped in exosomal membranes obtained from breast cancer cells (Ex@MTX-CQDs). Analysis utilizing nanoparticle tracking techniques has demonstrated that these Ex@MTX-CQDs maintain the physical and biochemical properties of their exosomal precursors. The release profile of MTX indicated a restricted release percentage (less than 10%) under normal physiological conditions, which is contrasted by a more consistent release rate (approximately 65%) when emulating the conditions found within tumor tissues. The toxicological assessments have confirmed that the presence of exosomes combined with leftover folic acid significantly improves the delivery efficacy of MTX directly to the cancerous cells through the binding to folate and heparan sulfate proteoglycan receptors. This process results in increased disruption of the mitochondrial membrane potential and subsequently triggers apoptosis, ultimately leading to the destruction of cancerous cells. Our research could potentially contribute to the further innovation and application of nanocarriers derived from biological sources for the targeted treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Aim: This study examined the levels of VitD, VitD binding protein (DBP), and free VitD in leiomyomas patients and their association with the quantity, dimensions, and site of fibroid growths. Additionally, we evaluated the potentiality of employing these factors as a biomarker tool for the diagnosis and assessment of uterine fibroid progression. Methods: This study involved the participation of 55 women with leiomyomas and 50 healthy women. We utilized commercial ELISA kits to measure the levels of total VitD and DBP in their serum. Additionally, we calculated the levels of free VitD and the ratio of VitD to DBP. Moreover, we determined the number, size, and location of the leiomyomas in the patients. Results: There were no significant differences in the levels of total VitD between the groups. However, patients had significantly lower levels of free VitD and higher levels of DBP compared to the control group. The size of the largest leiomyomas showed a negative relationship with free VitD and a positive relationship with DBP. Receiver operating characteristic analyses, showed that the cut‐off value for free VitD was 4.47 pg/mL, with a sensitivity of 75.6% and a specificity of 74.4%. The cut‐off value for DBP was 256.2 μg/mL, with a sensitivity of 86% and a specificity of 70.3%. Conclusions: Free VitD and DBP potentially contribute to the development of leiomyomas and are linked to the size of these tumors. The measurement of serum levels of these factors could serve as additional biomarkers for the diagnosis of leiomyomas. [ABSTRACT FROM AUTHOR]

Despite performing certain morphological assessments for selecting the best embryo for transfer, the results have not been satisfactory. Given the global tendency for performing quick and noninvasive tests for embryo selection, great efforts have been made to discover the predictive biomarkers of embryo implantation potential. In recent years, many factors have been detected in embryo culture media as a major source of embryo secretions. Previous studies have evaluated cytokines, miRNAs, extracellular vesicles, and other factors such as leukemia inhibitory factor, colony‐stimulating factor, reactive oxygen species, soluble human leukocyte antigen G, amino acids, and apolipoproteins in these media. Given the key role of cytokines in embryo implantation, these factors can be considered promising molecules for predicting the implantation success of assisted reproductive technology (ART). The present study was conducted to review embryo‐secreted molecules as potential biomarkers for embryo selection in ART. [ABSTRACT FROM AUTHOR]

Objectives: Hepatocellular carcinoma (HCC) is considered as the most incidence form of cancer in the human liver and the main reason for worldwide cancer death. In addition, HCC is a common form of cancer in Africa and Asia and a global health issue. Thus, efforts should be made to improve treatment strategies and prognosis in HCC for recognizing novel prognostic and predictive markers. Methods: The present study reviewed recently published studies that were identified from the National Institutes of Health's PubMed database, Latin American Literature in Health Sciences, and Scientific Electronic Library Online. To this end, several key terms were searched, including "hepatocellular carcinoma" AND "diagnosis" AND "hepatic resection", miRNA, and Mesh (Medical Subject Headings) consisting of miRNA "hepatocellular carcinoma". Results: Both physiological and pathological processes such as development can be altered by the function and expression modifying of miRNA. The findings revealed that miR-101, miR-106, miR-130a, miR-515-5p, miR-199a, and miR-34a-5p have a considerable connection with tumor size in HCC patients. Conclusions: In general, several reports indicated that more than half of the miRNAs genes are located in cancer-associated genomic regions or fragile sites. Considering the reports regarding the important roles of miRNAs in cancer, their potential as prognostic or diagnostics markers is confirmed by a long list of studies and miRNA markers that could be used for cancer diagnosis are becoming available [ABSTRACT FROM AUTHOR]

Introduction: Nowadays, mesenchymal stem cells are touted as suitable cell supply for the restoration of injured bone tissue. The existence of osteogenic differentiation makes these cells capable of replenishing damaged cells in the least possible time. It has been shown that epigenetic modifications, especially DNA methylation, contribute to the regulation of various transcription factors during phenotype acquisition. Hence, we concentrated on the correlation between the promoter methylation and the expression of genes DLX3, ATF4 , and FRA1 during osteoblastic differentiation of adipose-derived mesenchymal stem cells in vitro after 21 days. Methods: Adipose-derived mesenchymal stem cells were cultured in osteogenesis differentiation medium supplemented with 0.1 µM dexamethasone, 10 mM β-glycerol phosphate, and 50 µM ascorbate-2-phosphate for 21 days. RNA and DNA extraction was done on days 0, 7, 14, and 21. Promoter methylation and expression levels of genes DLX3 , ATF4 , and FRA1 were analyzed by methylation-specific quantitative PCR and real-time PCR assays, respectively. Results: We found an upward expression trend with the increasing time for genes DLX3, ATF4, and FRA1 in stem cells committed to osteoblast-like lineage compared to the control group (P <0.05). On the contrary, methylation-specific quantitative PCR displayed decreased methylation rates of DLX3 and ATF4 genes, but not FRA1 , over time compared to the non-treated control cells (P <0.05). Bright-field images exhibited red-colored calcified deposits around Alizarin Red S-stained cells after 21 days compared to the control group. Statistical analysis showed a strong correlation between the transcription of genes DLX3 and ATF4 and methylation rate (P <0.05). Conclusion: In particular, osteoblastic differentiation of adipose-derived mesenchymal stem cells enhances DLX3 and ATF4 transcriptions by reducing methylation rate for 21 days. [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD) is a common cause of morbidity and mortality worldwide. Atherosclerotic plaques, as a hallmark of CAD, cause chronic narrowing of coronary arteries over time and could also result in acute myocardial infarction (AMI). The standard treatments for ameliorating AMI are reperfusion strategies, which paradoxically result in ischemic reperfusion (I/R) injury. Sphingosine 1 phosphate (S1P), as a potent lysophospholipid, plays an important role in various organs, including immune and cardiovascular systems. In addition, high‐density lipoprotein, as a negative predictor of atherosclerosis and CAD, is a major carrier of S1P in blood circulation. S1P mediates its effects through binding to specific G protein‐coupled receptors, and its signaling contributes to a variety of responses, including cardiac inflammation, dysfunction, and I/R injury protection. In this review, we will focus on the role of S1P in CAD and I/R injury as a potential therapeutic target. Sphingosine 1 phosphate (S1P) mediates its effects through binding to specific G protein‐coupled receptors, and its signaling contributes to a variety of responses, including cardiac inflammation, dysfunction, and I/R injury protection. In this review, we will focus on the role of S1P in coronary artery disease and I/R injury as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

During embryo implantation, crosstalk between the endometrial epithelium and the blastocyst, especially the trophoblasts, is a prerequisite for successful implantation. During this crosstalk, various molecular and functional changes occur to promote synchrony between the embryo and the endometrium as well as the uterine cavity microenvironment. In the past few years, growing evidence has shown that endometrium‐derived exosomes play pivotal roles in the embryonic‐maternal crosstalk during implantation, although the exact mechanism of this crosstalk has yet to be determined. The presence of metalloproteinases has been reported in endometrium‐derived exosomes, implying the importance of these enzymes in exosome‐based crosstalk. Thus, in this review, we describe the potential roles of the metalloproteinases of endometrium‐derived exosomes in promoting embryo attachment and implantation. This study could provide a better understanding of the potential roles of exosomal metalloproteinases in embryo implantation and pave the way for developing novel exosome‐based regulatory agents to support early pregnancy. [ABSTRACT FROM AUTHOR]

Paraoxonase1 (PON1) is a glycoprotein associated with high density lipoprotein and has antioxidant activity. The impact of PON1 in various stages of spermatogenesis has also been suggested. This study was aimed to investigate frequencies of phenotypes and Q192R genotypes of PON1 in fertile and infertile males. Q192R variants of PON1 were determined in 150 fertile and 150 infertile men using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Plasma arylesterase and paraoxonase activities were detected by spectrophotometry and malondialdehyde (MDA) level was measured using thiobarbituric acid. Our results showed no significant difference in the distribution of PON1 genotypes and alleles between fertile and infertile groups. However morphology and motility of sperm were associated with various genotypes of PON1. The number of fertile males with the BB phenotype (high activity) was significantly higher than that of infertile males, whereas the number of individuals with the AB phenotype (moderate activity) was statistically higher in infertile men compared with the fertile group. Additionally, MDA and arylesterase activity levels were significantly higher in infertile subjects compared with fertile men. We speculate that the low activity of PON1 can be a risk factor for male infertility probably due to a decrease in antioxidant activity of PON1 and increase in lipid peroxidation. [ABSTRACT FROM AUTHOR]

Background: Vitamin D in complex with its receptor by regulating gene expression, endometrium immune response and stimulation of endometrium decidualization can be involved in implantation. So, it seems that the amount of vitamin D in follicular fluids (FF) may have an association with ART success. Objective: First, we intended to investigate the possible association between levels of follicular fluids 25-OH vitamin D with assisted reproductive outcomes. Second, we examined relationship between 25-OH vitamin D levels with number and quality of oocytes. Materials and Methods: In a prospective study, 80 infertile female candidates for IVF/ICSI were enrolled. Blood samples (on the day of human chorionic gonadotropin administration) and follicular fluids were taken, and then levels of serum estradiol and follicular fluids 25-OH vitamin D were measured. Also clinical characteristics of patients (duration of infertility, causes of infertility, menstrual status), number and quality of oocytes, number of fertilized oocytes, estradiol levels, and clinical pregnancy were evaluated. Results: Concentration of FF 25-OH vitamin D in pregnant women was significantly higher than non-pregnant women (p=0.007) but there were no significant differences in age, body mass index (BMI), duration of infertility, menstrual status, number of oocytes, oocytes quality, number of fertilized oocytes, and serum estradiol levels between the two groups. Statistically positive correlation was found between 25-OH vitamin D levels with patient age and implantation rate (r=0.264, p=0.018 and r=0.301, p=0.007 respectively). Conclusion: The obtained results suggest that vitamin D without affecting the number and quality of oocytes can independently improve implantation rate and IVF outcome. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a primary endocrinological disorder in women of reproductive age that is characterized by androgen excess and ovulatory irregularities. This syndrome is associated with adipose tissue dysfunction, an elevated risk of insulin resistance, hyperinsulinemia, obesity, and type 2 diabetes. Adipocyte dysfunction affects the secretion of adipokines and pro-inflammatory cytokines. Nevertheless, adipose tissue is not an exclusive source of adipokines as it can also be produced locally by reproductive tissues. Although adipokines have been recognized in the development of PCOS, the role of oncostatin M (OSM), a multifaceted adipokine, remains unclear. Current evidence suggests that this cytokine is associated with key aspects of the syndrome, including obesity, insulin resistance, hyperandrogenism, and inflammation. However, the data are often contradictory, likely due to variations in study designs, methodologies, and species differences. By investigating the link between OSM and PCOS-associated issues, this review identified the potential role of this adipokine in PCOS pathogenesis. This underscores the need for further research to clarify its predominant effects and assess its relevance as a therapeutic target.