Alanda (Ephedra foeminea) nanoparticles as a modulator of genomic DNA degradation in mice: new inspiration for treating Ehrlich solid tumour-induced kidney and liver toxicity.

OBJECTIVE: The limitations faced by conventional drug delivery systems are being overcome through the use of rapidly evolving cancer nanotherapeutics. Determining the manner in which the Ehrlich solid tumor (EST) is impacted by the new bioactive Alanda-loaded flax seed gum nanoparticles (Alanda NPs) functioning as an anti-carcinogenic agent represents the research objective of this paper. MATERIALS AND METHODS: Identification of the functional groups, surface morphology, particle size, and zeta potential were among the characterizations and preparations made for the prepared nanoparticles. A Control group, a Flax Seed Gum group, a raw Alanda group, an Alanda NPs group, an EST group, and an induced EST treated with Alanda NPs group comprised the six groups respectively which the 60 female mice were separated into in this in vivo study. RESULTS: Toxicity assessments for kidneys and liver were performed alongside the detection of total genomic DNA degradation. The zeta potential and the particle sizes for Alanda NPs were -25.60±0.38 mv and 40±0.28 nm, respectively, where the latter demonstrated a monodisperse spherical shape, per the findings. The use of Alanda NPs to treat EST was found to alle te the DNA damage, apoptosis, and renal and hepatic toxicity that EST induces. Additionally, the activation of oxidative stress and apoptosis causing the renal and hepatic toxicity induced by EST is counteracted by the scavenging of free radicals by the Alanda NPs. CONCLUSIONS: A high degree of safety for effective cancer treatment was displayed by the newly developed oral nanoparticles while also demonstrating strong potential in vivo.

O-GlcNAcylation of STAT5 controls tyrosine phosphorylation and oncogenic transcription in STAT5-dependent malignancies.

The signal transducer and activator of transcription 5 (STAT5) regulates differentiation, survival, proliferation and transformation of hematopoietic cells. Upon cytokine stimulation, STAT5 tyrosine phosphorylation (pYSTAT5) is transient, while in diverse neoplastic cells persistent overexpression and enhanced pYSTAT5 are frequently found. Post-translational modifications might contribute to enhanced STAT5 activation in the context of transformation, but the strength and duration of pYSTAT5 are incompletely understood. We found that O-GlcNAcylation and tyrosine phosphorylation act together to trigger pYSTAT5 levels and oncogenic transcription in neoplastic cells. The expression of a mutated hyperactive gain-of-function (GOF) STAT5 without O-GlcNAcylation resulted in decreased tyrosine phosphorylation, oligomerization and transactivation potential and complete loss of oncogenic transformation capacity. The lack of O-GlcNAcylation diminished phospho-ERK and phospho-AKT levels. Our data show that O-GlcNAcylation of STAT5 is an important process that contributes to oncogenic transcription through enhanced STAT5 tyrosine phosphorylation and oligomerization driving myeloid transformation. O-GlcNAcylation of STAT5 could be required for nutrient sensing and metabolism of cancer cells.

Effect of repeated sequential ejaculation on sperm DNA integrity in subfertile males with asthenozoospermia.

The aim of this work was to study the possible beneficial effect of repeated sequential ejaculation on sperm DNA integrity in subfertile males and its possible implementation in assisted reproduction. The study included 20 infertile males with idiopathic asthenozoospermia or oligoasthenozoospermia. They underwent detailed history taking, complete clinical assessment and hormonal assessment. Patients were asked to bring two semen samples (taken within 1-3 h). Two consecutive samples were assessed with regard to semen volume, sperm count, motility grading, and morphology and sperm DNA integrity using the comet assay. There was a significant improvement in the sperm motility pattern and DNA integrity in the second sample in comparison with the first sample. Therefore, it is concluded that due to its positive impact on sperm motility and DNA integrity, repeated sequential ejaculation is recommended in subfertile males with idiopathic asthenozoospermia who pursue assisted reproduction.