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The renaissance of research into natural products has unequivocally and paradigmatically shifted our knowledge about the significant role of natural products in cancer chemoprevention. Bufalin is a pharmacologically active molecule isolated from the skin of the toad Bufo gargarizans or Bufo melanostictus. Bufalin has characteristically unique properties to regulate multiple molecular targets and can be used to harness multi-targeted therapeutic regimes against different cancers. There is burgeoning evidence related to functional roles of signaling cascades in carcinogenesis and metastasis. Bufalin has been reported to regulate pleiotropically a myriad of signal transduction cascades in various cancers. Importantly, bufalin mechanistically regulated JAK/STAT, Wnt/β-Catenin, mTOR, TRAIL/TRAIL-R, EGFR, and c-MET pathways. Furthermore, bufalin-mediated modulation of non-coding RNAs in different cancers has also started to gain tremendous momentum. Similarly, bufalin-mediated targeting of tumor microenvironments and tumor macrophages is an area of exciting research and we have only started to scratch the surface of the complicated nature of molecular oncology. Cell culture studies and animal models provide proof-of-concept for the impetus role of bufalin in the inhibition of carcinogenesis and metastasis. Bufalin-related clinical studies are insufficient and interdisciplinary researchers require detailed analysis of the existing knowledge gaps.

ACSL4 (Acyl-CoA synthetase long chain family, member-4) METTL3 (Methyltransferase-like 3) FSP1 (ferroptosis suppressor protein 1) DKK1 (DICKKOPF1) GOT1 (glutamic-oxaloacetic transaminase 1) CAFs (Cancer-associated fibroblasts) GPX4 (glutathione peroxidase 4) TBLR1 (TBL1-related protein 1)

Background Although cochlear implantation (CI) has been performed in Kazakhstan since 2007 little is known about quality of life of patients after CI. The aim of this study was to assess the health-related quality of life (HRQoL) of Kazakhstani children after CI. Methods Altogether, 53 families with a child using a cochlear implant for at least 1 year participated in the study between July 20, 2019 and February 20, 2020 at the Audiological Сenter of Almaty, Kazakhstan. The parents/caregivers completed the “Children with Cochlear Implants: Parental Perspectives (CCIPP)” questionnaire. Results ‘Well-being and happiness’ subdomain of the HRQoL yielded the highest ratings. ‘Communication’, ‘general functioning’, ‘self-reliance’, and ‘supporting the child’ subdomains each achieved significant (p < 0.01) associations with all HRQoL subdomains. There were positive correlations between language used by the parent who completed the questionnaire (Kazakh or Russian) and three HRQoL subdomains, including ‘well-being and happiness’, ‘supporting the child’ and ‘social relations’. Conclusion Parents/caregivers reported high quality of life in all HRQoL subdomains. Further research in this area with more detailed socio-demographic and medical history data is required to identify quality of life predictors in children after cochlear implantation.

Landmark discoveries in molecular oncology have provided a wide-angle overview of the heterogenous and therapeutically challenging nature of cancer. The power of modern ‘omics’ technologies has enabled researchers to deeply and comprehensively characterize molecular mechanisms underlying cellular functions. Interestingly, high-throughput technologies have opened new horizons for the design and scientific fool-proof evaluation of the pharmacological properties of targeted chemical compounds to tactfully control the activities of the oncogenic protein networks. Groundbreaking discoveries have galvanized the expansion of the repertoire of available pharmacopoeia to therapeutically target a myriad of deregulated oncogenic pathways. Natural product research has undergone substantial broadening, and many of the drugs which constitute the backbone of modern pharmaceuticals have been derived from the natural cornucopia. Baicalein has gradually gained attention because of its unique ability to target different oncogenic signal transduction cascades in various cancers. We have partitioned this review into different sub-sections to provide a broader snapshot of the oncogenic pathways regulated by baicalein. In this review, we summarize baicalein-mediated targeting of WNT/β-catenin, AKT/mTOR, JAK/STAT, MAPK, and NOTCH pathways. We also critically analyze how baicalein regulates non-coding RNAs (microRNAs and long non-coding RNAs) in different cancers. Finally, we conceptually interpret baicalein-mediated inhibition of primary and secondary growths in xenografted mice.