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The mRNA expression levels of phospholipase Cγ1 (PLCG1) are much higher in IDH wild-type (IDHwt) lower-grade gliomas (LGGs) than in that of IDH mutant (IDHmut) LGGs. Higher PLCG1expression in IDHwt LGGs indicates poor clinical outcome. PLCG1 amplification may act as the key mechanism of PLCG1 upregulation. Depletion of PLCG1 expression can inhibits proliferation and invasion of IDHwt LGG cell lines in vitro and in vivo. The PLC inhibitor U73122 may therefore be a potential therapeutical agent for IDHwt LGGs.
Mother-to-child transmission is the major cause of chronic hepatitis B virus (HBV) infection. This study shows that an unconventional protein secretion pathway that depends on autophagy may be hijacked by HBV to complete the process of intracellular transport. In HBV-infected trophoblasts, AnxA2-S100A10-mediated exocytosis may result in HBV intrauterine transmission.
Pharmacological inhibition of the serine synthesis pathway with a highly selective inhibitor NCT503 synergistically works with temozolomide in inhibiting O6-methylguanine DNA methyltransferase (MGMT)-positive glioblastoma cell growth and inducing apoptosis both in vitro and in vivo. Mechanistically, NCT503 treatment reduces MGMT expression possibly via Wnt/βcatenin pathway. Reactive oxygen species-mediated DNA damage is at least partially involved. Combinational administration of NCT503 and TMZ may represent a novel and promising treatment strategy to enhance TMZ efficacy in patients with MGMT-high glioblastoma.
Adrenomedullin (ADM) significantly stimulates osteoclastogenesis only in the presence of calcitonin. Functional ADM receptor partly composed of osteoclast-specific cell surface Kat1 antigen was detected in cells in the osteoclast-lineage. Expression of ADM receptor was firstly detected in proliferating osteoclast progenitors performing asymmetric cell division and is then expressed in mononuclear osteoclast precursors. Specific regulation of ADM receptors expressed on mononuclear osteoclast precursors could provide an alternative way to modulate bone remodeling therapeutically.
The prevalence and contribution of viruses to heart failure phenotypes are increasingly recognized, while still underappreciated and underreported. We designed a tissue microarray with cardiac muscle tissue from 78 heart failure patients and probed for common cardiotropic viruses via in situ hybridization. Viral RNA was detected in 46.4% of patients, higher than anticipated for these heart failure conditions that include those not previously associated with a viral trigger or an exacerbating role.
This report provides new evidence supporting the role of ATP synthase inhibitory factor subunit 1 (IF1), an endogenous ATP synthase inhibitory protein, in regulating β-cell function. Investigations on genetic mouse models and an β-cell line indicate that IF1 negatively regulates cellular respiration and mitochondrial homeostasis, thus controlling insulin storage and release from islets.
The authors developed a deep convolutional neural network-based algorithm to support pathological muscle diagnosis. The algorithm differentiated idiopathic inflammatory myopathies and outperformed nine human physicians under limited diseases and conditions. These results suggest that the algorithm has the potential to be used directly in clinical settings.
It is unclear how to best classify cancer outcomes using ‘omic data. We developed a multimetric feature-selection based multinomial logistic regression model that outperformed random forest models in classifying 4-category outcome of colorectal cancer. Adding microsatellite instability and oncogenic-driver data to clinical and transcriptomic data improves models’ performances, with pathologic staging, HBS1L, TSPYL4, and TP53TG3B as important features. Interestingly, precision and recall of tuned algorithms change as the feature number changes, but accuracy does not.
Extensive morphological analysis demonstrates the importance of tunneling nanotubes for intercellular communication in osteoclast differentiation, especially in the fusion process of osteoclast precursors. Successful detection of nanotubes was also demonstrated in cultured primary osteoclasts resorbing dentin slices, and in osteoclasts in bone destruction sites of arthritic rats. Tunneling nanotubes are important for the differentiation of osteoclasts, both in vitro and in vivo.
The authors investigated the contribution of yes associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) in osteocyte mechanotransduction. In a 3-D osteocyte compression model, they show that YAP/TAZ signaling is activated, is required for osteocyte mechano-responsiveness, and regulates the expression profile of target genes as shown by RNAseq analysis and the control of chemokine expression.
In this study, the authors demonstrated that bioactive glass promotes granulation formation, collagen deposition and angiogenesis to accelerate wound healing. Bioactive glass down-regulaties the connexin 43/reactive oxygen species signaling pathway to inhibit endothelial cell pyroptosis in vitro and in vivo.
Chronic mineral-oil intraperitoneal administration induces hepatic inflammation through innate immune responses via myeloid cell activation. Lcn2 null mice develop less inflammation due to defective genes involved in myeloid cell activation, and downregulated gene sets for collagen-containing extracellular matrix, leading to mitigation of the liver fibrosis. Lcn2 null mice show enriched expression of genes responsible for DNA damage and cell cycle DNA replication compared to wild-type upon chronic CCl4 liver injury.
Ameloblastoma (AB) is the most common benign odontogenic tumor. In this study, we investigated the expression and distribution of acetylated α-tubulin and αTAT1 in AB specimens. We analyzed tubulin acetylation caused by αTAT1 activation in a human AB cell line, AM-1. Results of the histopathological and in vitro studies clarified that TAK1 was phosphorylated by TGF-β stimulation, then, induced tubulin acetylation via αTAT1 activation, which subsequently activated the migration and invasion of AB cells.
Bone morphogenetic protein (BMP) induces epithelial–mesenchymal transition (EMT) both B16 mouse and A2058 human melanoma cell lines. The injection of B16 cells expressing constitutively activated ALK3 enhanced zygoma destruction compared with empty B16 cells, suggesting that the activation of BMP signaling enhances bone invasion by inducing EMT in melanoma cells.
Vitamin D has recently emerged as a neurosteroid and a regulator of various physiological functions. It has been widely reported to promote tumor-suppressive effects, however this proposal remains controversial. This article reviews the anti-tumoral mechanisms of vitamin D in glioblastoma, current evidence of its therapeutic application as a supplement to standard chemotherapy, and its potential applications for cancer prevention; it endeavors to offer insight into new means of overcoming chemoresistance and improving glioma patient survival.
The 5th edition of WHO Classification of Tumors of the Central Nervous System adopted new molecular markers into the revised grading criteria of IDH-mutant and -wild-type astrocytoma, i.e., the CDKN2A/B homozygous deletion for IDH-mutant astrocytoma and the following three criteria for IDH-wild-type astrocytoma: the concurrent gain of whole chromosome 7 and loss of whole chromosome 10, TERT promoter mutations, and EGFR amplification, as independent molecular markers of the highest grade.
