Search

More couples worldwide, delay their childbearing years. The increase in age causes a gradual decrease in female ovarian function and fertility, leading to an exponential decrease in women over 35 years of age having children. Although promising for some, assisted reproductive technology (ART) is not promising for older women. Decreased fertility in advanced age has become a growing concern in the field of reproduction. In this study, high-throughput transcriptome sequencing was used to identify the differentially expressed genes (DEGs) in the ovarian granulosa cells (GCs) of older women (aged 35–44) with infertility and younger women (aged 25–34). The enriched functions and signaling pathways of DEGs were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The function of DEGs were analyzed and predicted combined with clinical ART data. Sequencing results were verified by quantitative reverse transcription-polymerase chain reaction. Retrospective clinical data and bioinformatics analyses revealed marked reductions in the retrieved oocyte, metaphase II oocyte, 2PN fertilization, and effective embryo numbers in older women. Although the clinical pregnancy and live birth rates did not differ notably between the groups, the miscarriage rate increased significantly in older women. In total, 620 DEGs were identified, of which 246 were upregulated, and 374 were downregulated in the older group. GO, and KEGG analyses indicated that the mechanism of fertility decline in older women was probably related to chronic inflammation, cytokine receptor interaction, and oxidative stress. In conclusion, combined with basic clinical ART data and pregnancy outcomes, we tried to provide a more intuitive and in-depth understanding of age-related reduction in ovarian function and pathogenesis of infertility with regard to chronic inflammation and oxidative stress. [ABSTRACT FROM AUTHOR]

Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 mounts specific acid-resistance systems against acid stress, making it more difficult to eradicate in food industry. To date, RNAseq-based analysis focusing on the virulence factors within an acidic environment is restricted to asmall part of virulence gene clusters. In this study E.coli O157:H7 survived HCl stress at pH 3.0 for up to 1 h preceded by acid adaptation at pH 5.5 for 1 h. At the same time, bacteria without stimulus were cultured in neutral TSB broth for 2 h.Then, transcriptome analysis was performed to compare virulence-related genes at neutral and acidic pH. Though transcripts indicated adownshift of the flagellar, fimbriae and LEE-associated genes, the increased expression of adhesin-related genes, iron uptake genes and some potential virulence factors were identified. Comparison of the gene expression with respect to virulence factors revealed strongest cell response to the relevant stress and increased protective response for survival in the acidic pH. This suggests that E.coli O157:H7 might be still virulent following HCl stress. [ABSTRACT FROM AUTHOR]

Background: The development of nanoparticle drug delivery systems with targeted ligands has the potential to increase treatment efficiency in ovarian cancer. Methods: We developed a 21-amino acid peptide, YTRDLVYGDPARPGIQGTGTF (L-FP21) conjugated to polyethylenimine (PEI) and methoxy polyethylene glycol (mPEG) to prepare a nanoparticle drug vehicle to target follicle-stimulating hormone receptor (FSHR) in ovarian cancer. At the same time, we optimized the ligand of the nanoparticle vehicle using D-peptides, which consist of D-amino acids (D-FP21). Nanoparticle vehicles carrying the therapeutic gene plasmid growth-regulated oncogene alpha (pGRO-α) short hairpin RNA (shRNA) (FP21-PEG-PEI/pGRO-α) were prepared for further investigation. Results: Compared with L-FP21, D-FP21 exhibited improved biological stability and higher uptake rate for FSHR-expressing ovarian cancer cells. The cytotoxicity of the L, D-FP21-PEG-PEI/pGRO-α complexes were significantly lower than that of the PEI/pGRO-α complex. The nanoparticle drug with the targeted ligand showed higher transfection efficiencies and improved anti-proliferation effects for ovarian cancer cells than that without the targeted ligand (mPEG-PEI/pGRO-α). Furthermore, an in vivo evaluation of an antitumor assay indicated that D-FP21-PEG-PEI/pGRO-α inhibited the growth of tumor spheroids considerably more than L-FP21-PEG-PEI/pGRO-α; their tumor inhibition rates were 58.5% and 33.3%, respectively. Conclusions: D-FP21-PEG-PEI/plasmid DNA is a safe and efficient gene delivery vehicle for ovarian cancer targeted therapy. [ABSTRACT FROM AUTHOR]