Pharmacological Insights: Mitochondrial ROS Generation by FNC (Azvudine) in Dalton's Lymphoma Cells Revealed by Super Resolution Imaging.

Nucleoside analogs are a common form of chemotherapy that disrupts DNA replication and repair, leading to cell cycle arrest and apoptosis. Reactive oxygen species (ROS) production is a significant mechanism through which these drugs exert their anticancer effects. This study investigated a new nucleoside analog called FNC or Azvudine, and its impact on ROS production and cell viability in Dalton's lymphoma (DL) cells. The study found that FNC treatment resulted in a time- and dose-dependent increase in ROS levels in DL cells. After 15 and 30 min of treatment with 2 and 1 mg/ml of FNC, mitochondrial ROS production was observed in DL cells. Furthermore, prolonged exposure to FNC caused structural alterations and DNA damage in DL cells. The results suggest that FNC's ability to impair DL cell viability may be due to its induction of ROS production and indicate a need for further investigation.

Safety Assessment of a Nucleoside Analogue FNC (2'-deoxy-2'- ß-fluoro-4'-azidocytidine ) in Balb/c Mice: Acute Toxicity Study.

OBJECTIVES: The present study aimed to provide an insight into the acute toxicity of a novel fluorinated nucleoside analogue (FNA), FNC (Azvudine or2'-deoxy-2'-ß-fluoro-4'-azidocytidine). FNC showed potent anti-viral and anti-cancer activities and approved drug for high-load HIV patients, despite, its acute toxicity study being lacking. MATERIALS AND METHODS: OECD-423 guidelines were followed during this study and the parameters were divided into four categories - behavioral parameters, physiological parameters, histopathological parameters, and supplementary tests. The behavioral parameters included feeding, body weight, belly size, organ weight and size, and mice behavior. The physiological parameters consisted of blood, liver, and kidney indicators. In histopathological parameters hematoxylin and eosin staining was performed to analyse the histological changes in the mice organs after FNC exposure. In addition, supplementary tests were conducted to assess cellular viability, DNA fragmentation and cytokine levels (IL-6 and TNF-α) in response to FNC. RESULTS: In the behavioral parameters FNC induced changes in the mice-to-mice interaction and activities. Mice's body weight, belly size, organ weight, and size remained unchanged. Physiological parameters of blood showed that FNC increased the level of WBC, RBC, Hb, and neutrophils and decreased the % count of lymphocytes. Liver enzymes SGOT (AST), and ALP was increased. In the renal function test (RFT) cholesterol level was significantly decreased. Histopathological analysis of the liver, kidney, brain, heart, lungs, and spleen showed no sign of tissue damage at the highest FNC dose of 25 mg/kg b.wt. Supplementary tests for cell viability showed no change in viability footprint, through our recently developed dilution cum-trypan (DCT) assay, and Annexin/PI. No DNA damage or apoptosis was observed in DAPI or AO/EtBr studies. Pro-inflammatory cytokines IL-6 and TNF-α increased in a dose-dependent manner. CONCLUSION: This study concluded that FNC is safe to use though higher concentration shows slight toxicity.

A 1.1 Mb duplication CNV on chromosome 17 contributes to skeletal muscle development in Boer goats.

The Boer goat is one of the top meat breeds in modern animal husbandry and has attracted widespread attention for its unique growth performance. However, the genetic basis of muscle development in the Boer goat remains obscure. In this study, we identified specific structural variants in the Boer goat based on genome-wide selection signals and analyzed the basis of the molecular heredity of related candidate genes in muscle development. A total of 9 959 autosomal copy number variations (CNVs) were identified through selection signal analysis in 127 goat genomes. Specifically, we confirmed that the highest signal CNV (HSV) was a chromosomal arrangement containing an approximately 1.11 Mb (CHIR17: 60062304-61171840 bp) duplicated fragment inserted in reverse orientation and a 5 362 bp deleted region (CHIR17:60145940-60151302 bp) with overlapping genes (e.g., ARHGAP10, NR3C2, EDNRA, PRMT9, and TMEM184C). The homozygous duplicated HSV genotype (+/+) was found in 96% of Boer goats but was not detected in Eurasian goats and was only detected in 4% of indigenous African goats. The expression network of three candidate genes ( ARHGAP10, NR3C2, and EDNRA) regulating dose transcription was constructed by RNA sequencing. Results indicated that these genes were involved in the proliferation and differentiation of skeletal muscle satellite cells (SMSCs) and their overexpression significantly increased the expression of SAA3. The HSV of the Boer goat contributed to superior skeletal muscle growth via the dose effects of overlapping genes.