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Akt kinase is vital in cell growth, survival, metabolism, and migration. Dysregulation of Akt signaling is implicated in cancer and metabolic disorders. In the context of cancer, overactive Akt promotes cell survival and proliferation. This has spurred extensive research into developing Akt inhibitors as potential therapeutic agents to disrupt aberrant Akt signaling. Akt inhibitors are classified into three main types: ATP-competitive, allosteric, and covalent-allosteric inhibitors (CAAIs). ATP-competitive inhibitors compete with ATP for binding to Akt, allosteric inhibitors interact with the Pleckstrin homology (PH) domain, and covalent-allosteric inhibitors form covalent bonds, making them more potent and selective. Notably, capivasertib (AZD5363), a potent ATP-competitive Akt inhibitor, received FDA approval in November 2023 for use in combination with the estrogen receptor degrader fulvestrant to treat breast cancer. Challenges remain, including improving selectivity, identifying biomarkers to tailor treatments, and enhancing therapeutic efficacy while minimizing adverse effects. Particularly covalent-allosteric inhibitors hold promise for future more effective and personalized treatments.

At present, the growing spread of tumor cases worldwide renders the research of new promising and selective anticancer drugs urgent. The biological action of extracts of medicinal plants or their essential oils (EOs) is an emerging field of interest, since they could comprise a rich source of phytochemicals that can prove promising. In the present study, the biological activity and mechanism of action of the EO of Foeniculum vulgare subsp. piperitum fruits (FVPEO) were investigated using MTT assays, morphological analyses and western blotting in MDA‑MB231 cells, a triple‑negative breast cancer cell line. The findings revealed that FVPEO could exert strong anticancer effects, causing a dose‑dependent inhibition of breast cancer MDA‑MB231 cell growth, accompanied with DNA condensation and fragmentation. The cytotoxic effect of FVPEO was counteracted by the addition of the antioxidant N‑acetylcysteine and was associated with a marked increase in reactive oxygen species and stress‑related proteins; such as manganese superoxide dismutase, c‑Jun, phospho‑c‑Jun N‑terminal kinase and nuclear factor E2‑related factor 2, and the latter's transcriptional targets, Heme oxygenase‑1 and NAD(P)H quinone oxidoreductase 1 (NQO1). As evidenced by the activation of caspase‑3 and fragmentation of poly(ADP‑ribose) polymerase‑1, which are typical apoptosis markers, FVPEO promoted apoptotic cell death accompanied with an increase in phosphorylated H2A histone family member X and the activation of the NQO1/p53 axis. In combination, the present experiments provided evidence that FVPEO could represent a reservoir of biologically active compounds suitable for both cancer prevention and treatment.

Background: Congenital heart disease is a common birth defect rather than a paediatric disease. Parents often discover this disease after their children's birth and then often learn that cardiac surgery is the only solution. A child's admission to a paediatric cardiac intensive care unit (PCICU) may lead to high levels of stress, anxiety and depression in parents., Objectives: To describe the lived experiences of mothers and fathers during their children's confinement in a PCICU., Methods: A phenomenological study was conducted. This method combines descriptive features (Husserlian) and interpretive phenomenology (Gadamerian). The subjects were interviewed with open questions to allow them full freedom of expression and were asked to describe their experiences when their children were admitted to the PCICU. Each interview was audio-recorded and lasted between 20 and 60 minutes. The researchers involved in the analysis each independently immersed themselves in the data by reading and re-reading the transcripts in order to gain a sense of the whole dataset. The extrapolation of the themes followed. The individual researchers compared the various extrapolated themes., Results: We enrolled 16 participants. Three main themes emerged: 1) the fear of the potential loss of their children, (2) the feeling of having lost their roles as parents and (3) the desire to receive more information and be an active part of the treatment process., Conclusion: A child's admission to a PCICU requires healthcare staff to take care of the child's family members as well. Knowing about mothers' and fathers' experiences is crucial in implementing a holistic and multidisciplinary process of care., (Copyright © 2018 Elsevier Inc. All rights reserved.)