Quercetin elevates p27Kip1 and arrests both primary and HPV16 E6/E7 transformed human keratinocytes in G1

Our previous work with primary bovine fibroblasts demonstrated that quercetin, a potent mutagen found in high levels in bracken fern (Pteridium aquilinum), arrested cells in G1 and G2/M, in correlation with p53 activation. The expression of bovine papillomavirus type 4 (BPV-4) E7 overcame this arrest and lead to the development of tumorigenic cells lines (Beniston et al., 2001). Given the possible link between papillomavirus infection, bracken fern in the diet and cancer of the upper gastrointestinal (GI) tract in humans, we investigated whether a similar situation would occur in human cells transformed by human papillomavirus type 16 (HPV-16) oncoproteins. Quercetin arrested primary human foreskin keratinocytes in G1. Arrest was linked to an elevation of the cyclin-dependent kinase inhibitor (cdki) p27Kip1. Expression of the HPV16 E6 and E7 oncoproteins in transformed cells failed to abrogate cell cycle arrest. G1 arrest in the transformed cells was also linked to an increase of p27Kip1 with a concomitant reduction of cyclin E-associated kinase activity. This elevation of p27Kip1 was due not only to increased protein half-life, but also to increased mRNA transcription

Do NSAIDs Prevent Colorectal Cancer?

There is increasing evidence to suggest that acetylsalicylic acid (ASA) and other nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of colorectal cancer. This observation is supported by animal studies that show fewer tumours per animal and fewer animals with tumours after administration of several different NSAIDs. Studies in humans consistently support this hypothesis. Intervention data from familial adenomatosis coli establish that the process of human colonic adenoma polyp formation is affected. Supportive evidence comes from 21 of 23 human studies -- both case-control and cohort. The reduced risk has been found in men and women, for cancers of the colon and the rectum and for the use of both ASA and the other NSAIDs. Earlier detection of lesions as a result of drug-induced bleeding does not seem to account for these findings. The molecular mechanisms responsible for the chemopreventive action of this class of drugs is not completely established. Protection may affect several pathways, including cell cycle arrest and induction of apoptosis.  Because of the consistency of epidemiological, clinical and experimental data, there is no need for further placebo trials. At the same time, there is a need to establish the dose, duration and frequency of use required for cancer-preventive activity

The Big Potential of Small Particles: Lipid-Based Nanoparticles and Exosomes in Vaccination

Some of the most significant medical achievements in recent history are the development of distinct and effective vaccines, and the improvement of the efficacy of previously existing ones, which have contributed to the eradication of many dangerous and life-threatening diseases. Immunization depends on the generation of a physiological memory response and protection against infection. It is therefore crucial that antigens are delivered in an efficient manner, to elicit a robust immune response. The recent approval of COVID-19 vaccines containing lipid nanoparticles encapsulating mRNA demonstrates the broad potential of lipid-based delivery systems. In light of this, the present review article summarizes currently synthesized lipid-based nanoparticles such as liposomes, lipid-nano particles, or cell-derived exosomes

Impaired bone healing at tooth extraction sites in CD24-deficient mice: A pilot study

<div><p>Aim</p><p>To use a micro-computed tomography (micro-CT) to quantify bone healing at maxillary first molar extraction sites, and test the hypothesis that bone healing is impaired in <i>CD24</i>-knockout mice as compared with wild-type C57BL/6J mice.</p><p>Materials and methods</p><p>Under ketamine-xylazine general anaesthesia, mice had either extraction of the right maxillary first molar tooth or sham operation. Mice were sacrificed 1 (n = 12/group), 2 (n = 6/group) or 4 (n = 6/group) weeks postoperatively. The right maxillae was disected. Micro-CT was used to quantify differences in bone microstructural features at extrction sites, between <i>CD24</i>-knockout mice and wild-type mice.</p><p>Results</p><p><i>CD24</i>-Knockout mice displayed impaired bone healing at extraction sites that was manifested as decreased trabecular bone density, and decreased number and thickness of trabeculae.</p><p>Conclusions</p><p>This pilot study suggests that CD24 plays an important role in extraction socket bone healing and may be used as a novel biomarker of bone quality and potential therapeutic target to improve bone healing and density following alveolar bone injury.</p></div

Behavioral Characterizing of CD24 Knockout Mouse—Cognitive and Emotional Alternations

CD24 is a small, glycophosphatidylinositol-anchored cell surface protein, mostly investigated with respect to cancer, inflammation, and autoimmune diseases. CD24 knockdown or inhibition has been used to test various biochemical mechanisms and neurological conditions; however, the association between CD24 and behavioral phenotypes has not yet been examined. This study aims to characterize cognitive and emotional functions of CD24 knockout mice (CD24−/− )compared with CD24 wild-type mice at three time-points: adolescence, young adulthood, and adulthood. Our results show that CD24−/− mice exhibited better cognitive performance and less anxiety-like behavior compared with WT mice, with no effect on depression-like behavior. This phenotype was constant from childhood (2 months old) to adulthood (6 months old). The results from our study suggest that CD24 may influence important behavioral aspects at the whole-organism level, which should be taken into consideration when using CD24 knockout models

Behavioral Characterizing of CD24 Knockout Mouse—Cognitive and Emotional Alternations

CD24 is a small, glycophosphatidylinositol-anchored cell surface protein, mostly investigated with respect to cancer, inflammation, and autoimmune diseases. CD24 knockdown or inhibition has been used to test various biochemical mechanisms and neurological conditions; however, the association between CD24 and behavioral phenotypes has not yet been examined. This study aims to characterize cognitive and emotional functions of CD24 knockout mice (CD24−/− )compared with CD24 wild-type mice at three time-points: adolescence, young adulthood, and adulthood. Our results show that CD24−/− mice exhibited better cognitive performance and less anxiety-like behavior compared with WT mice, with no effect on depression-like behavior. This phenotype was constant from childhood (2 months old) to adulthood (6 months old). The results from our study suggest that CD24 may influence important behavioral aspects at the whole-organism level, which should be taken into consideration when using CD24 knockout models