Surface decoration by Spirulina polysaccharide enhances the cellular uptake and anticancer efficacy of selenium nanoparticles

A simple and solution-phase method for functionalization of selenium nanoparticles (SeNPs) with Spirulina polysaccharides (SPS) has been developed in the present study. The cellular uptake and anticancer activity of SPS-SeNPs were also evaluated. Monodisperse and homogeneous spherical SPS-SeNPs with diameters ranging from 20 nm to 50 nm were achieved under optimized conditions, which were stable in the solution phase for at least 3 months. SPS surface decoration significantly enhanced the cellular uptake and cytotoxicity of SeNPs toward several human cancer cell lines. A375 human melanoma cells were found extremely susceptible to SPS-SeNPs with half maximal (50%) inhibitory concentration value of 7.94 μM. Investigation of the underlying mechanisms revealed that SPS-SeNPs inhibited cancer cell growth through induction of apoptosis, as evidenced by an increase in sub-G1 cell population, deoxyribonucleic acid fragmentation, chromatin condensation, and phosphatidylserine translocation. Results suggest that the strategy to use SPS as a surface decorator could be an effective way to enhance the cellular uptake and anticancer efficacy of nanomaterials. SPS-SeNPs may be a potential candidate for further evaluation as a chemopreventive and chemotherapeutic agent against human cancers

eIF4A inhibitors suppress cell-cycle feedback response and acquired resistance to CDK4/6 inhibition in cancer

CDK4/6 inhibitors are FDA-approved drugs for estrogen receptor-positive (ER+) breast cancer and are being evaluated to treat other tumor types, including KRAS-mutant non-small cell lung cancer (NSCLC). However, their clinical utility is often limited by drug resistance. Here, we sought to better understand the resistant mechanisms and help devise potential strategies to overcome this challenge. We show that treatment with CDK4/6 inhibitors in both ER+ breast cancer and KRAS-mutant NSCLC cells induces feedback upregulation of cyclin D1, CDK4, and cyclin E1, mediating drug resistance. We demonstrate that rocaglates, which preferentially target translation of key cell-cycle regulators, effectively suppress this feedback upregulation induced by CDK4/6 inhibition. Consequently, combination treatment of CDK4/6 inhibitor palbociclib with the eukaryotic initiation factor (eIF) 4A inhibitor, CR-1-31-B, is synergistic in suppressing the growth of these cancer cells in vitro and in vivo Furthermore, ER+ breast cancer and KRAS-mutant NSCLC cells that acquired resistance to palbociclib after chronic drug exposure are also highly sensitive to this combination treatment strategy. Our findings reveal a novel strategy using eIF4A inhibitors to suppress cell-cycle feedback response and to overcome resistance to CDK4/6 inhibition in cancer.Accepted manuscrip

Influence of lifestyle on suboptimal health: Insights from a national cross-sectional survey in China

Background: Suboptimal health status (SHS) is a non-clinical or pre-disease state between optimal/ideal health and disease. While its etiology remains unclear, lifestyle is considered one of the most important risk factors. We aimed to examine the effects of lifestyles on SHS through a nationwide survey in China. Methods: We conducted a cross-sectional survey in 148 cities across China between 20 June and 31 August 2022, on 30 505 participants from rural and urban communities gathered through stratified quota sampling. We measured SHS with the Short-Form Suboptimal Health Status Questionnaire (SHSQ-SF). We gathered information on participants\u27 lifestyles (ie, smoking, alcohol consumption, breakfast habits, weekly food delivery frequency, intermittent fasting, sleep duration and physical activities) through face-to-face interview. We determined the relationship between lifestyle and SHS logistic regression analysis by based on odds ratios (ORs) and 95% confidence intervals (CIs). Results: We included 22 897 participants (female: 13 056, male: 9841), 12 108 (52.88%) of whom reported exposure to SHS. After adjusting for demographic characteristics, individuals who currently smoked (OR = 1.165; 95% CI = 1.058-1.283) and those who drank alcohol (OR = 1.483; 95% CI = 1.377.1.596) were at a higher risk of SHS than those who have never done either. In a dose-response way, takeaway food consumption was associated with a higher risk of SHS, while increased frequency of breakfast and mild-intensity exercise conversely reduced said risk. Individuals with shorter sleep duration had a higher risk of SHS when compared to those who slept for more than seven hours per day. Conclusions: We observed a relatively high prevalence of SHS across China, highlighting the importance of lifestyle in health promotion. Specifically, adopting healthy dietary habits, engaging in regular physical activity, and ensuring high-quality sleep are key in preventing SHS. Registration: Chinese Clinical Trial Registry (ChiCTR2200061046)

Selenium nanoparticles decorated with Ulva lactuca polysaccharide potentially attenuate colitis by inhibiting NF-κB mediated hyper inflammation

Additional file 1. Supplemental information of ULP-SeNPs concerns their stability in physiological solutions, uptake by BMDMs and effect on NF-κB activation

On the Origin of the Strong Optical Variability of Emission-line Galaxies

Emission-line galaxies (ELGs) are crucial in understanding the formation and evolution of galaxies, while little is known about their variability. Here we report the study on the optical variability of a sample of ELGs selected in the COSMOS field, which has narrow-band observations in two epochs separated by $\gtrsim$ 12 years. This sample was observed with Suprime-Cam (SC) and Hyper Suprime-Cam (HSC) on the $Subaru$ telescope in NB816 and $i'/i$ bands, respectively. After carefully removing the wing effect of a narrow-band filter, we check the optical variability in a sample of 181 spectroscopically confirmed ELGs. We find that 0 (0/68) Ha emitters, 11.9% (5/42) [OIII] emitters, and 0 (0/71) [OII] emitters show significant variability ($|\Delta m_{NB}| \geq 3\,\sigma_{\Delta m_{NB,AGN}} = 0.20\, mag$) in the two-epoch narrow-band observations. We investigate the presence of active galactic nucleus (AGN) in this variable ELG (var-ELG) sample with three methods, including X-ray luminosity, mid-infrared activity, and radio-excess. We find zero bright AGN in this var-ELG sample, but cannot rule out the contribution from faint AGN. We find that SNe could also dominate the variability of the var-ELG sample. The merger morphology shown in the HST/F814W images of all the var-ELG sample is in agreement with the enhancement of star formation, i.e., the SNe activity.Comment: 20 pages, 10 figures, accepted for publication in The Astrophysical Journa

Effects of Gualou Guizhi Decoction Aqueous Extract on Axonal Regeneration in Organotypic Cortical Slice Culture after Oxygen-Glucose Deprivation

Gualou Guizhi decoction (GLGZD) is effective for the clinical treatment of limb spasms caused by ischemic stroke, but its underlying mechanism is unclear. Propidium iodide (PI) fluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), immunohistochemistry, western blot, and real-time qPCR were used to observe the axonal regeneration and neuroprotective effects of GLGZD aqueous extract on organotypic cortical slices exposed to oxygen-glucose deprivation (OGD) and further elucidate the potential mechanisms. Compared with the OGD group, the GLGZD aqueous extract decreased the red PI fluorescence intensity; inhibited neuronal apoptosis; improved the growth of slice axons; upregulated the protein expression of tau and growth-associated protein-43; and decreased protein and mRNA expression of neurite outgrowth inhibitor protein-A (Nogo-A), Nogo receptor 1 (NgR1), ras homolog gene family A (RhoA), rho-associated coiled-coil-containing protein kinase (ROCK), and phosphorylation of collapsin response mediator protein 2 (CRMP2). Our study found that GLGZD had a strong neuroprotective effect on brain slices after OGD injury. GLGZD plays a vital role in promoting axonal remodeling and functional remodeling, which may be related to regulation of the expression of Nogo-A and its receptor NgR1, near the injured axons, inhibition of the Rho-ROCK pathway, and reduction of CRMP2 phosphorylation