Over the last decade immunotherapy has revolutionized the treatment of many cancers, especially with the better understanding of molecular biology and immunology. Programmed death 1 (PD-1) is an inhibitory cell-surface receptor expressed on the surface of T cells, B cells, and natural-killer cells. The effector functions of T cells that express PD-1 in the tumor microenvironment can be downregulated upon activation by its ligands (PD-L1 or PD-L2), which are expressed by the tumoral cells. Cytotoxic...
1h
Main points Host microbiota shape maturation and function of microglia during homeostatic conditions. Short‐chain fatty acids restore deficits in microglia from germ‐free housed mice. Host bacteria might influence several CNS diseases via microglia Abstract Among the myeloid cells in the central nervous system (CNS) microglia are the main representatives of the innate immune system. Microglial fulfil tasks beyond phagocytosing debris and host defense against invading microorganism....
1h
Lipopolysaccharide treatment could exacerbate neuroinflammation and dopaminergic neuron degeneration in Nurr1 Cd11bcre conditional knockout mice. Abstract Nuclear receptor‐related 1 protein (NURR1) is essential for the development and maintenance of midbrain dopaminergic (DAergic) neurons. NURR1 also protects DAergic neurons against neuroinflammation. However, it remains to be determined to what extent does NURR1 exerts its protective function through acting autonomously in the microglia....
1h
Glia cells participate in [K+]o management. The Na+/K+‐ATPase serves as key in this process, aided by temporally restricted spatial buffering. The associated glia swelling occurs not as function of K+ uptake or AQP4, but indirectly via cotransporters. Abstract Neuronal signaling in the central nervous system (CNS) associates with release of K+ into the extracellular space resulting in transient increases in [K+]o. This elevated K+ is swiftly removed, in part, via uptake by neighboring glia...
1h
(a) RUNX1 is higher in expression at the RNA level than RUNX2 in MCF10AT1. RUNX3 is not expressed. (b‐c) While, RUNX1 is lower in the CD24‐low BCSC subpopulation than CD24+/high cells, RUNX2 is increased. (d) The RUNX2 interaction network is the top significant pathway altered in ingenuity pathway anslysis of RNA‐seq comparing these two populations of cells. (e) Finally, by inhibiting both RUNX1 and RUNX2 binding to CBFβ, we determine that loss of RUNX1, rather than increase in RUNX2, is a driver...
1h
It is not clear how Lewy body (cellular inclusion with protein aggregation) occurs in Parkinson's disease (PD). We demonstrated that pharmacological inhibition of GTP‐binding by GTP‐binding inhibitors (68 and Fx2149) increased leucine‐rich repeat kinase 2 (LRRK2)‐linked ubiquitination and protein aggregation predominantly via K27 linkage. These studies provide novel insight into the LRRK2‐linked Lewy body‐like inclusion formation underlying PD pathogenesis. Abstract Parkinson's disease (PD) is...
1h
This report showed a possible evidence thatWD repeat domain 12 (WDR12) drove malignant behavior of GBM, whose expression may present a neoteric independent prognostic biomarker in GBM. Abstract Glioblastoma (GBM) is the most malignant primary brain tumor in adults. Due to its invasive nature, it cannot be thoroughly eliminated. WD repeat domain 12 (WDR12) processes the 32S precursor rRNA but cannot affect the synthesis of the 45S/47S primary transcript. In this study, we found that WDR12 is highly...
22h
Abstract Rapid progress in knowledge of the organization of the dog genome has facilitated the identification of the mutations responsible for numerous monogenic diseases, which usually present a breed-specific distribution. The majority of these diseases have clinical and molecular counterparts in humans. The affected dogs have thus become valuable models for preclinical studies of gene therapy for problems such as eye diseases, immunodeficiency, lysosomal storage diseases, hemophilia,...
2h
Background Among Latinas with breast cancer, residence in an ethnic enclave may be associated with survival. However, findings from prior studies are inconsistent. Methods The authors conducted parallel analyses of California and Texas cancer registry data for adult (aged ≥18 years) Latinas who were diagnosed with invasive breast cancer from 1996 to 2005, with follow‐up through 2014. Existing indices applied to tract‐level 2000 US Census data were used to measure Latinx enclaves and neighborhood...
2h
Abstract Estragole, naturally occurring in a variety of herbs and spices, can form DNA adducts after bioactivation. Estragole DNA adduct formation and repair was studied in in vitro liver cell models, and a molecular dynamics simulation was used to investigate the conformation dependent (in)efficiency of N2-(trans-isoestragol-3′-yl)-2′-deoxyguanosine (E-3′-N2-dG) DNA adduct repair. HepG2, HepaRG cells, primary rat hepatocytes and CHO cells (including CHO wild-type and three NER-deficient...
2h
Abstract P-glycoprotein (P-gp) is an ABC transporter exhibiting high pharmacotoxicological relevance by extruding a wide range of cytotoxic compounds out of the cells. Previously, we demonstrated that the phytoestrogen genistein (GNT) modulates P-gp expression in hepatocellular carcinoma in vitro. Although several beneficial effects (e.g., antioxidant, antimutagenic, anticancer) have been attributed to GNT, the molecular mechanisms have not been totally elucidated. In the present...
2h
Abstract Doxorubicin is a widely used anticancer drug that causes dose-related cardiotoxicity. The exact mechanisms of doxorubicin toxicity are still unclear, partly because most in vitro studies have evaluated the effects of short-term high-dose doxorubicin treatments. Here, we developed an in vitro model of long-term low-dose administration of doxorubicin utilizing human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Moreover, given that current strategies...
10h
Traditional Chinese medicine: The current name for an ancient system of health care from China. Traditional Chinese medicine (TCM) is based on a concept of balanced qi (pronounced "chee"), or vital energy, that is believed to flow throughout the body. Qi is proposed to regulate a person's spiritual, emotional, mental, and physical balance and to be influenced by the opposing forces of yin (negative energy) and yang (positive energy). Disease is proposed to result from the flow of qi being disrupted...
2h
Abstract Diagnostic ultrasound has accurately and reliably been utilized by clinicians to determine ACL morphology at the tibial insertion site, specifically measuring the entire ACL diameter, the anteromedial bundle (AM), and the posterolateral bundle. However, intra- and inter-rater reliability of these measures in a research setting is unknown. The purpose of this study was to determine intra- and inter-rater reliability of ultrasound measures of ACL diameter and AM diameter...
3h
Abstract High-resolution ultrasonography (US) is a valuable tool in breast imaging. Nevertheless, US is an operator-dependent technique: to overcome this issue, the American College of Radiology (ACR) has developed the breast imaging-reporting and data system (BI-RADS) US lexicon. Despite this effort, the variability in the assessment of focal breast lesions (FBLs) with the use of BI-RADS US lexicon is still an issue. Within this framework, evidence shows that computer-aided image...
15h
Abstract Purpose We aimed to investigate the use and effectiveness of Shear-Wave Elastography (SWE) in Hashimoto’s Thyroiditis (HT) diagnosis and compare the SWE values in HT patients with asymptomatic volunteers. Methods The thyroid gland parenchyma of 74 patients whose clinical and laboratory findings and ultrasonography (US) features were indicative of...
17h
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