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  • Barrera Jorgensen posted an update 10 days ago

    qPCR and western blot suggested that Klotho and Nrf2 expression in MΦ1 cells of BSA-KL-/+ mice was significantly decreased. Thus, the findings suggest during the immune activation and chronic inflammation induced by the gut microbiota imbalance in Klotho-deficient mice treated to BSA, disrupted expression of proteins in the Nrf2/NF-κB signaling pathway in monocyte-derived macrophage M1 cells leads to the aggravation of inflammation and kidney injury.Visualization of cell-cycle G1 phase for monitoring the early response of cell cycle specific drug remains challenging. In this study, we developed genetically engineered bioluminescent reporters by fusing full-length cyclin E to the C-terminal luciferase (named as CycE-Luc and CycE-Luc2). Next, HeLa cell line or an ER-positive breast cancer cell line MCF-7 was transfected with these reporters. In cellular assays, the bioluminescent signal of CycE-Luc and CycE-Luc2 was accumulated in the G1 phase and decreased after exiting from the G1 phase. The expression of CycE-Luc and CycE-Luc2 fusion protein was regulated in a cell cycle-dependent manner, which was mediated by proteasome ubiquitination and degradation. Next, our in vitro and in vivo experiment confirmed that the cell cycle arrested by anti-cancer agents (palbociclib or 5-FU) was monitored quantitatively and dynamically by bioluminescent imaging of these reporters in a real-time and non-invasive manner. Thus, these optical reporters could reflect the G1 phase alternation of cell cycle, and might become a future clinically translatable approach for predicting and monitoring response to palbociclib in patients with ER-positive breast cancer.Tight junction (TJ) is a “zippering up” junction structure located at the uppermost portion of adjacent epithelial/endothelial cells in organs and tissues. TJs maintain the relative stability of intracellular substances and functions by closing or opening intercellular pathways, coordinating the entry and exit of molecules of different sizes and charges, and regulating the permeability of paracellular barrier. TJs also prevent microbial invasion, maintain epithelial/endothelial cell polarity, and regulate cell proliferation. TJs are widely present in the skin and mucosal epithelial barriers, intestinal epithelial barrier, glomerular filtration barrier, bladder epithelial barrier, blood-brain barrier, brain-blood tumor barrier, and blood-testis barrier. TJ dysfunction in different organs can lead to a variety of diseases. In addition to signal pathways, transcription factors, DNA methylation, histone modification, TJ proteins can also be regulated by a variety of non-coding RNAs, such as micro-RNAs, long-noncoding RNAs, and circular RNAs, directly or indirectly. This review summarizes the structure of TJs and introduces the functions and regulatory mechanisms of TJs in different organs and tissues. The roles and mechanisms of non-coding RNAs in the regulation of TJs are also highlighted in this review.Background Head and neck squamous cell carcinoma (HNSCC) are head and neck cancers. On the other hand, ferroptosis is a novel iron-dependent and ROS reliant type of cell death observed various disease conditions. Method We constructed a prognostic multilncRNA signature based on ferroptosis-related differentially expressed lncRNAs in HNSCC. Results We identified 25 differently expressed lncRNAs associated with prognosis of HNSCC. Kaplan-Meier analyses revealed the high-risk lncRNAs signature associated with poor prognosis of HNSCC. Moreover, the AUC of the lncRNAs signature was 0.782, underscoring their utility in prediction HNSCC prognosis. Indeed, our risk assessment model was superior to traditional clinicopathological features in predicting HNSCC prognosis. GSEA revealed the immune and tumor-related pathways in the low risk group individuals. Moreover, TCGA revealed T cell functions including cytolytic activity, HLA, regulation of inflammationp, co-stimulation, co-inhibition and coordination of type II INF response were significantly different between the low-risk and high-risk groups. Immune checkpoints such as PDCD-1 (PD-1), CTLA4 and LAG3, were also expressed differently between the two risk groups. Conclusion A novel ferroptosis-related lncRNAs signature impacts on the prognosis of HNSCC.Although germline mutations in BRCA1 highly predispose women towards breast and ovarian cancer, few substantial improvements in preventing or treating such cancers have been made. Importantly, BRCA1 function is closely associated with DNA damage repair, which is required for genetic stability. Here, we examined the efficacy of radiotherapy, assessing the accumulation of genetic instabilities, in the treatment of BRCA1-associated breast cancer using a Brca1-mutant mouse model. Treatment of Brca1-mutant tumor-engrafted mice with X-rays reduced tumor progression by 27.9% compared with untreated controls. A correlation analysis of irradiation responses and biomarker profiles in tumors at baseline identified differences between responders and non-responders at the protein level (pERα, pCHK2, p53, and EpCAM) and at the SOX2 target expression level. We further demonstrated that combined treatment of Brca1-mutant mammary tumors with irradiation and AZD2281, which inhibits PARP, significantly reduced tumor progression and extended survival. Our findings enhance the understanding of DNA damage and biomarker responses in BRCA1-associated mammary tumors and provide preclinical evidence that radiotherapy with synthetic DNA damage is a potential strategy for the therapeutic management of BRCA1-associated breast cancer.This was a national survey that determined the prevalence of depressive symptoms (depression thereafter) and its relationship with quality of life (QOL) in frontline clinicians working in psychiatric hospitals in China during the COVID-19 pandemic. Depression and QOL were assessed using the Patient Health Questionnaire nine items (PHQ-9) and the World Health Organization Quality of Life Questionnaire-brief version (WHOQOL-BREF), respectively. Multivariable logistic regression analyses and analysis of covariance were used. Dyngo-4a inhibitor A total of 10,516 frontline clinicians participated in this study, of which, 28.52% (n=2,999) met screening criteria for depression. Compared to those without depression, clinicians with depression had a lower quality of life (F (1, 10515) =2874.66, P less then 0.001). Higher educational level (OR=1.225, P=0.014), if the number of COVID-19 patients in the hospital catchment area surpassed 500 (OR=1.146, P=0.032), having family/friends/colleagues who were infected (OR=1.695, P less then 0.001), being a current smoker (OR=1.

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