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Silver nanoparticles (AgNPs) have attracted increased interest and are currently used in various industries including medicine, cosmetics, textiles, electronics, and pharmaceuticals, owing to their unique physical and chemical properties, particularly as antimicrobial and anticancer agents. Recently, several studies have reported both beneficial and toxic effects of AgNPs on various prokaryotic and eukaryotic systems. To develop nanoparticles for mediated therapy, several laboratories have used a variety of cell lines under in vitro conditions to evaluate the properties, mode of action, differential responses, and mechanisms of action of AgNPs. In vitro models are simple, cost-effective, rapid, and can be used to easily assess efficacy and performance. The cytotoxicity, genotoxicity, and biocompatibility of AgNPs depend on many factors such as size, shape, surface charge, surface coating, solubility, concentration, surface functionalization, distribution of particles, mode of entry, mode of action, growth media, exposure time, and cell type. Cellular responses to AgNPs are different in each cell type and depend on the physical and chemical nature of AgNPs. This review evaluates significant contributions to the literature on biological applications of AgNPs. It begins with an introduction to AgNPs, with particular attention to their overall impact on cellular effects. The main objective of this review is to elucidate the reasons for different cell types exhibiting differential responses to nanoparticles even when they possess similar size, shape, and other parameters. Firstly, we discuss the cellular effects of AgNPs on a variety of cell lines; Secondly, we discuss the mechanisms of action of AgNPs in various cellular systems, and try to elucidate how AgNPs interact with different mammalian cell lines and produce significant effects; Finally, we discuss the cellular activation of various signaling molecules in response to AgNPs, and conclude with future perspectives on research into AgNPs. [ABSTRACT FROM AUTHOR]

Recent advances in nanoscience and nanotechnology radically changed the way we diagnose, treat, and prevent various diseases in all aspects of human life. Silver nanoparticles (AgNPs) are one of the most vital and fascinating nanomaterials among several metallic nanoparticles that are involved in biomedical applications. AgNPs play an important role in nanoscience and nanotechnology, particularly in nanomedicine. Although several noble metals have been used for various purposes, AgNPs have been focused on potential applications in cancer diagnosis and therapy. In this review, we discuss the synthesis of AgNPs using physical, chemical, and biological methods. We also discuss the properties of AgNPs and methods for their characterization. More importantly, we extensively discuss the multifunctional bio-applications of AgNPs; for example, as antibacterial, antifungal, antiviral, anti-inflammatory, anti-angiogenic, and anti-cancer agents, and the mechanism of the anti-cancer activity of AgNPs. In addition, we discuss therapeutic approaches and challenges for cancer therapy using AgNPs. Finally, we conclude by discussing the future perspective of AgNPs. [ABSTRACT FROM AUTHOR]

Cervical cancer ranks seventh overall among all types of cancer in women. Although several treatments, including radiation, surgery and chemotherapy, are available to eradicate or reduce the size of cancer, many cancers eventually relapse. Thus, it is essential to identify possible alternative therapeutic approaches for cancer. We sought to identify alternative and effective therapeutic approaches, by first synthesizing palladium nanoparticles (PdNPs), using a novel biomolecule called saponin. The synthesized PdNPs were characterized by several analytical techniques. They were significantly spherical in shape, with an average size of 5 nm. Recently, PdNPs gained much interest in various therapies of cancer cells. Similarly, histone deacetylase inhibitors are known to play a vital role in anti-proliferative activity, gene expression, cell cycle arrest, differentiation and apoptosis in various cancer cells. Therefore, we selected trichostatin A (TSA) and PdNPs and studied their combined effect on apoptosis in cervical cancer cells. Cells treated with either TSA or PdNPs showed a dose-dependent effect on cell viability. The combinatorial effect, tested with 50 nM TSA and 50 nMPdNPs, had a more dramatic inhibitory effect on cell viability, than either TSA or PdNPs alone. The combination of TSA and PdNPs had a more pronounced effect on cytotoxicity, oxidative stress, mitochondrial membrane potential (MMP), caspase-3/9 activity and expression of pro- and anti-apoptotic genes. Our data show a strong synergistic interaction between TSA and PdNPs in cervical cancer cells. The combinatorial treatment increased the therapeutic potential and demonstrated relevant targeted therapy for cervical cancer. Furthermore, we provide the first evidence for the combinatory effect and cytotoxicity mechanism of TSA and PdNPs in cervical cancer cells. [ABSTRACT FROM AUTHOR]

Due to their unique physical, chemical, and optical properties, gold nanoparticles (AuNPs) have recently attracted much interest in the field of nanomedicine, especially in the areas of cancer diagnosis and photothermal therapy. Because of the enormous potential of these nanoparticles, various physical, chemical, and biological methods have been adopted for their synthesis. Synthetic antioxidants are dangerous to human health. Thus, the search for effective, nontoxic natural compounds with effective antioxidative properties is essential. Although AuNPs have been studied for use in various biological applications, exploration of AuNPs as antioxidants capable of inhibiting oxidative stress induced by heat and cold stress is still warranted. Therefore, one goal of our study was to produce biocompatible AuNPs using biological methods that are simple, nontoxic, biocompatible, and environmentally friendly. Next, we aimed to assess the antioxidative effect of AuNPs against oxidative stress induced by cold and heat in Escherichia coli, which is a suitable model for stress responses involving AuNPs. The response of aerobically grown E. coli cells to cold and heat stress was found to be similar to the oxidative stress response. Upon exposure to cold and heat stress, the viability and metabolic activity of E. coli was significantly reduced compared to the control. In addition, levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and leakage of proteins and sugars were significantly elevated, and the levels of lactate dehydrogenase activity (LDH) and adenosine triphosphate (ATP) significantly lowered compared to in the control. Concomitantly, AuNPs ameliorated cold and heat-induced oxidative stress responses by increasing the expression of antioxidants, including glutathione (GSH), glutathione S-transferase (GST), super oxide dismutase (SOD), and catalase (CAT). These consistent physiology and biochemical data suggest that AuNPs can ameliorate cold and heat stress-induced oxidative damage in E. coli. Our results indicate that AuNPs may be effective antioxidants. However, further studies are needed to confirm the role of AuNPs as antioxidative agents, as well as their mechanism of action. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA), a chemical used in many consumer products, interferes with the endocrine system of mammals, including humans. The aim of the present study was to investigate the effect of BPA on spermatogenesis and semen quality. The objective of this study was to assess the effects of BPA on mouse spermatogenesis. CD1 mice were used in all experiments. Mice were treated with different doses of BPA (0, 20 and 40 µg kg[sup -1] day[sup -1]from postnatal Day (PND) 3 to PND21, PND 35 or PND49. After 5 weeks BPA treatment, oestrogen receptor α expression was increased in mouse testis, whereas the meiotic progression of germ cells was slowed. Thus, both the quality and quantity of spermatozoa were decreased in 7-week-old mice. However, BPA had no effect on DNA methylation of imprinted genes such as Igf2, Igf2r, Peg3 and H19, in germ cells. In addition, exposure of male mice to BPA resulted in abnormal offspring that were smaller with a low-quality pelage when they were 35 days old. In conclusion, BPA hampers spermatogenesis and the subsequent development of offspring. Bisphenol A (BPA), a chemical used in many consumer products, interferes with the endocrine system of mammals, including humans. The present study investigated the effects of BPA on spermatogenesis and semen quality, and found that BPA decreased both the quantity and quality of mouse spermatozoa, resulting in abnormal offspring that were smaller and had a low-quality pelage. The results demonstrate that BPA hampers spermatogenesis and the development of offspring. [ABSTRACT FROM AUTHOR]

Background: Polysaccharides have various biological activities; the complexation of polysaccharides with trace element ions can produce synergistic effects, improving the original biological activities of sugars and trace elements. Methods: The preparation process of chitosan oligosaccharide selenium (COSSe) was optimized by the response surface method, followed by a detailed analysis of the resultant compound's characteristics. The anti-cancer activity of COSSe was studied using the human ovarian cancer cell line SKOV3 as a cell model. Results: The prepared COSSe response surface was well predicted, indicating successful chitosan oligosaccharide binding with selenium. Response surface method analyses identified the optimal synthesis conditions for COSSe: the reaction time of 5.08 h, the reaction temperature of 71.8 °C, and mass ratio (Na2SeO3: chitosan oligosaccharide) of 1.02. Under the optimal conditions, the final product, the selenium content, reached 1.302%. The results of cell experiments showed that COSSe significantly inhibited SKOV3 proliferation in a concentration-dependent manner. RNA-seq results showed that chitosan oligosaccharide and COSSe significantly modulated the expression of genes' DNA metabolic processes and cell cycle in SKOV3 cells. Gene enrichment analysis showed the inhibition of the cell cycle, and the results of flow cytometry showed that SKOV3 cells increased in the S phase and decreased in the G2/M phase, with a noted suppression in the protein expression of cyclin-dependent kinase 2 (CDK2) and cyclin A1 (CCNA1). Conclusion: COSSe has a stronger effect than chitosan oligosaccharide, leading to the arrest of the cell cycle in the S phase. Thus, COSSe may be an effective candidate for the treatment of ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: The male reproductive system consists of the testes, epididymis, accessorygonads, and genital ducts. The physiological integrity of the testicles is essential forsuccessful sperm production, but the testes are susceptible to a variety of exogenous andendogenous toxins, which can lead to structural damage to tissues and spermabnormalities. Spermatogenesis is always in a homeostatic process and is sensitive to changes intheexternal environment. Huperzia serrata flavonoids (HSF) have a variety of pharmacological effects, including the treatment of bruises, strains, etc. HSF can improve the reproductivefunction of male mice, so the purpose of this experiment is to explore whether huperzineflavonoids are involved in and regulate the male reproductive process. Methods: Ourexperimental animals were ICR mice, and samples were collected after 28 days of HSFtreatment, and verified by a series of experimental methods such as immunofluorescence, immunohistochemistry, HE staining, protein hybridization, and screening of relatedgenes. Results: RNA sequencing results showed that HSF up-regulated genes related to spermdevelopment and differentiation in testes and promoted spermatogenesis. HSF is effectiveinpromoting steroid hormone synthesis by modulating STAR, CYP11A1, and CYP17A1. Conclusion: Thus, HSF can regulate testicular gene expression, stabilize the gut microbiome, alter serum metabolites, and regulate steroid homeostasis. [ABSTRACT FROM AUTHOR]

Background: Lotus root polysaccharide is a natural antioxidant. As a new anticancer drug, it has anti-proliferation and pro-apoptotic effects in a variety of tumour cells, but its effect on ovarian cancer is not clear. In study, we attempted to elucidate the role and mechanism of lotus root polysaccharide in SKOV3 cells. Methods: In this study, the effect of lotus root polysaccharide on mRNA of SKVO3 cells was analyzed by RNA-seq, and verified by Western blot, flow cytometry, fluorescence detection and other techniques. Results: The results showed that lotus root polysaccharide could inhibit the proliferation of ovarian cancer cells. Then, a change in gene expression was found by RNA-seq. In the mRNA (differentially expressed mRNA) with these differences, significant changes in the cell cycle were found by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Subsequently, the proportion of cells in S phase decreases and G2/M phase increases, as seen with propidium iodide staining. Gene Set Enrichment Analysis showed inhibition of the cell cycle, and the gene and protein expression of CDK1, CCNA1 and CCNB1 were inhibited. Conclusion: Our results show that lotus root polysaccharide can inhibit the growth of SKOV3 cells in vitro by blocking the cell cycle at the G2/M phase, which reveals the potential of lotus root polysaccharide in the treatment of ovarian cancer. [ABSTRACT FROM AUTHOR]

Zearalenone (ZEN), one of the most prevalent non-steroidal oestrogenic mycotoxins, is primarily produced by Fusarium fungi. Due to its toxicity as an oestrogenic compound and wide distribution in feed and foods, the reproductive toxicology of ZEN exposure is of public concern. The aim of the present study was to investigate the effect of ZEN on Sertoli cells to identify apoptotic pathways induced by this compound. We found that ZEN reduced the viability and caused apoptosis in Sertoli cells in vitro. Notably, we observed that such effects were associated with a significant increase in reactive oxygen species (ROS) and the number of cells that showed positive staining for γH2AX and RAD51, enzymes essential for repairing DNA damage. There was a parallel decrease in the expression of occludin and connex- in 43, proteins that are present in the testis--blood barrier and gap junctions of Sertoli cells, respectively. Overall, the present study confirms that ZEN exposure can have serious deleterious effects on mammalian Sertoli cells and offers novel insight about its molecular targets in these cells. [ABSTRACT FROM AUTHOR]

In the present study, we established an in vitro culture system suitable for generating fertilizable oocytes from premeiotic mouse female germ cells. These results were achieved after first establishing an in vitro culture system allowing immature oocytes from 12-14 day- old mice to reach meiotic maturation through culture onto preantral granulosa cell (PAGC) monolayers in the presence of Activin A (ActA). To generate mature oocytes from premeiotic germ cells, pieces of ovaries from 12.5 days post coitum (dpc) embryos were cultured in medium supplemented with ActA for 28 days and the oocytes formed within the explants were isolated and cocultured onto PAGC monolayers in the presence of ActA for 6-7 days. The oocytes were then subjected to a final meiotic maturation assay to evaluate their capability to undergo germinal vesicle break down (GVBD) and reach the metaphase II (MII) stage. We found that during the first 28 days of culture, a significant number of oocytes within the ovarian explants reached nearly full growth and formed preantral follicle-like structures with the surrounding somatic cells. GSH level and Cx37 expression in the oocytes within the explants were indicative of proper developmental conditions. Moreover, the imprinting of Igf2r and Peg3 genes in these oocytes was correctly established. Further culture onto PAGCs in the presence of ActA allowed about 16% of the oocytes to undergo GVBD, among which 17% reached the MII stage during the final 16-18 hr maturation culture. These MII oocytes showed normal spindle and chromosome assembly and a correct ERK1/2 activity. About 35% of the in vitro matured oocytes were fertilized and 53.44% of them were able to reach the 2-cell stage. Finally, around 7% of the 2-cell embryos developed to the morula/blastocyst stage. [ABSTRACT FROM AUTHOR]

The Notch and transforming growth factor (TGF)-b signalling pathways play an important role in granulosa cell proliferation. However, the mechanisms underlying the cross-talk between these two signalling pathways are unknown. Herein we demonstrated a functional synergism between Notch and TGF-b signalling in the regulation of preantral granulosa cell (PAGC) proliferation. Activation of TGF-b signalling increased hairy/enhancer-of-split related with YRPW motif 2 gene (Hey2) expression (one of the target genes of the Notch pathway) in PAGCs, and suppression of TGF-b signalling by Smad3 knockdown reduced Hey2 expression. Inhibition of the proliferation of PAGCs by N-[N-(3,5- difluorophenacetyl)-L-alanyl]-S-phenylglycine z-butylester (DAPT), an inhibitor of Notch signalling, was rescued by both the addition of ActA and overexpression of Smad3, indicating an interaction between the TGF-b and Notch signalling pathways. Co-immunoprecipitation (CoIP) and chromatin immunoprecipitation (ChIP) assays were performed to identify the point of interaction between the two signalling pathways. CoIP showed direct protein-protein interaction between Smad3 and Notch2 intracellular domain (NICD2), whereas ChIP showed that Smad3 could be recruited to the promoter regions of Notch target genes as a transcription factor. Therefore, the findings of the present study support the idea that nuclear Smad3 protein can integrate with NICD2 to form a complex that acts as a transcription factor to bind specific DNA motifs in Notch target genes, such as Hey1 and Hey2, and thus participates in the transcriptional regulation of Notch target genes, as well as regulation of the proliferation of PAGCs. [ABSTRACT FROM AUTHOR]

The growth of oocytes and the development of follicles require certain pathways involved in cell proliferation and survival, such as the phosphatidylinositol 3-kinase (PI3K) pathway and the Notch signalling pathway. The aim of the present study was to investigate the interaction between Notch and the PI3K/AKT signalling pathways and their effects on primordial follicle recruitment.When the Notch pathway was inhibited by L-685,458 or N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycinet-butyl ester (DAPT) in vitro, the expression of genes in the pathway and the percentage of oocytes in growing follicles decreased significantly in mouse ovaries. By 2 days postpartum, ovaries exposed to DAPT, short interference (si) RNA against Notch1 or siRNA against Hairy and enhancer of split-1 (Hes1) had significantly decreased expression of HES1, the target protein of the Notch signalling pathway. In contrast, expression of phosphatase and tensin homologue (Pten), a negative regulator of the AKT signalling pathway, was increased significantly. Co immunoprecipitation (Co-IP) revealed an interaction between HES1 and PTEN. In addition, inhibition of the Notch signalling pathway suppressed AKT phosphorylation and the proliferation of granulosa cells. In conclusion, the recruitment of primordial follicles was affected by the proliferation of granulosa cells and regulation of the interaction between the Notch and PI3K/AKT signalling pathways. [ABSTRACT FROM AUTHOR]