Blocking Deoxycytidine Kinase in Activated Lymphocytes Depletes Deoxycytidine Triphosphate Pools and Alters Cell Cycle Kinetics to Yield Less Disease in a Mouse Multiple Sclerosis Model.

Autoreactive, aberrantly activated lymphocytes that target myelin antigens in the central nervous system (CNS) are primary drivers of the autoimmune disease multiple sclerosis (MS). Proliferating cells including activated lymphocytes require deoxyribonucleoside triphosphates (dNTPs) for DNA replication. dNTPs can be synthesised via the de novo pathway from precursors such as glucose and amino acids or the deoxyribonucleoside salvage pathway from extracellular deoxyribonucleosides.

Pacritinib inhibits glucose consumption in squamous cell lung cancer cells by targeting FLT3.

Squamous cell lung cancer maintains its growth through elevated glucose consumption, but selective glucose consumption inhibitors are lacking. Here, we discovered using a high-throughput screen new compounds that block glucose consumption in three squamous cell lung cancer cell lines and identified 79 compounds that block glucose consumption in one or more of these cell lines. Based on its ability to block glucose consumption in all three cell lines, pacritinib, an inhibitor of FMS Related Receptor Tyrosine Kinase 3 (FLT3) and Janus Kinase 2 (JAK2), was further studied.

Targeting deoxycytidine kinase improves symptoms in mouse models of multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease driven by lymphocyte activation against myelin autoantigens in the central nervous system leading to demyelination and neurodegeneration. The deoxyribonucleoside salvage pathway with the rate-limiting enzyme deoxycytidine kinase (dCK) captures extracellular deoxyribonucleosides for use in intracellular deoxyribonucleotide metabolism. Previous studies have shown that deoxyribonucleoside salvage activity is enriched in lymphocytes and required for early lymphocyte development.

GLUT1 overexpression enhances glucose metabolism and promotes neonatal heart regeneration.

The mammalian heart switches its main metabolic substrate from glucose to fatty acids shortly after birth. This metabolic switch coincides with the loss of regenerative capacity in the heart. However, it is unknown whether glucose metabolism regulates heart regeneration.

Rapid, efficient, and economical synthesis of PET tracers in a droplet microreactor: application to O-(2-[F]fluoroethyl)-L-tyrosine ([F]FET).

Background: Conventional scale production of small batches of PET tracers (e.g. for preclinical imaging) is an inefficient use of resources.

A high-throughput screen identifies that CDK7 activates glucose consumption in lung cancer cells.

Elevated glucose consumption is fundamental to cancer, but selectively targeting this pathway is challenging. We develop a high-throughput assay for measuring glucose consumption and use it to screen non-small-cell lung cancer cell lines against bioactive small molecules. We identify Milciclib that blocks glucose consumption in H460 and H1975, but not in HCC827 or A549 cells, by decreasing SLC2A1 (GLUT1) mRNA and protein levels and by inhibiting glucose transport.

F-FAC PET Visualizes Brain-Infiltrating Leukocytes in a Mouse Model of Multiple Sclerosis.

Brain-infiltrating leukocytes contribute to multiple sclerosis (MS) and autoimmune encephalomyelitis and likely play a role in traumatic brain injury, seizure, and stroke. Brain-infiltrating leukocytes are also primary targets for MS disease-modifying therapies. However, no method exists for noninvasively visualizing these cells in a living organism.

[Leaf functional traits and nutrient resorption among major silviculture tree species in coastal sandy site.].

To understand the adaptative strategies of different tree species to drought and nutrient-deficient environment in coastal sandy site, leaf functional traits and nutrient resorption of four major silviculture tree species, i.e., Casuarina equisetifolia, Pinus elliottii, Acasia crassicarpa and Eucalyptus urophylla × E.

Incidence and radiological pattern of eosinophilic granuloma: a retrospective study in a Chinese tertiary hospital.

Background: The incidence and radiological patterns of eosinophilic granuloma (EG) in China is not clear. We described the incidence, presentation, and imaging characteristics of Chinese EG patients in a tertiary hospital.

Methods: A retrospective chart review was performed from January 2004 to October 2017 at a single tertiary general hospital.

[Treatment of thoracolumbar burst fractures with intelligent inflated reduction combined with percutaneous pedicle screw fixation].

Objective: To evaluate the clinical outcome of intelligent inflated reduction combined with percutaneous pedicle screw fixation in treating thoracolumbar burst fractures.

Methods: The clinical data of 22 patients with thoracolumbar burst fractures of single segment treated from January 2013 to December 2015 were retrospectively analyzed. There were 12 males and 10 females, aged from 32 to 56 years old with an average of (42.

F-FAC PET Selectively Images Liver-Infiltrating CD4 and CD8 T Cells in a Mouse Model of Autoimmune Hepatitis.

Immune cell-mediated attack on the liver is a defining feature of autoimmune hepatitis and hepatic allograft rejection. Despite an assortment of diagnostic tools, invasive biopsies remain the only method for identifying immune cells in the liver. We evaluated whether PET imaging with radiotracers that quantify immune activation (F-FDG and F-1-(2'-deoxy-2'-fluoro-arabinofuranosyl)cytosine [F-FAC]) and hepatocyte biology (F-2-deoxy-2-fluoroarabinose [F-DFA]) can visualize and quantify liver-infiltrating immune cells and hepatocyte inflammation, respectively, in a preclinical model of autoimmune hepatitis.

Noninvasive Imaging of Drug-Induced Liver Injury with F-DFA PET.

Drug-induced liver failure is a significant indication for a liver transplant, and unexpected liver toxicity is a major reason that otherwise effective therapies are removed from the market. Various methods exist for monitoring liver injury but are often inadequate to predict liver failure. New diagnostic tools are needed.

Inhibitory effects of low decibel infrasound on the cardiac fibroblasts and the involved mechanism.

Introduction: Infrasound is a mechanical vibration wave with frequency between 0.0001 and 20 Hz. It has been established that infrasound of 120 dB or stronger is dangerous to humans.

Intravoxel incoherent motion diffusion-weighted MR imaging of gliomas: efficacy in preoperative grading.

The preoperative grading of gliomas, which is critical for guiding therapeutic strategies, remains unsatisfactory. We aimed to retrospectively assess the efficacy of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) in the grading of gliomas. Forty-two newly diagnosed glioma patients underwent conventional MR imaging, DWI, and contrast-enhanced MR imaging.

Predicting subtypes of thymic epithelial tumors using CT: new perspective based on a comprehensive analysis of 216 patients.

It is highly necessary to identify low versus high risk thymic epithelial tumors (TETs) before operation to guide optimal treatment strategies. Current CT diagnostic parameters could not effectively achieve this goal. We evaluated three parameters of CT scan in a cohort of 216 TETs patients.

Proliferative phenotype of pulmonary microvascular endothelial cells plays a critical role in the overexpression of CTGF in the bleomycin-injured rat.

The pathogenesis of idiopathic pulmonary fibrosis (IPF) is not very clear, with evidence for the involvement of both inflammation and aberrant vascular remodeling (associated with angiogenesis). Pulmonary microvascular endothelial cells (PMVECs), which play a major role in inflammation, secrete cytokines that promote the transformation and collagen synthesis of fibroblasts. Moreover, angiogenesis is characterized by PMVEC proliferation.

DLC-1 expression levels in breast cancer assessed by qRT- PCR are negatively associated with malignancy.

Objective: The aim of this study was to explore the expression of DLC-l in breast carcinoma and any association with tumor metastasis.

Methods: 51 surgical specimens of human breast carcinoma, divided into high invasive and low invasive groups according to their clinicopathological features, 30 cases of adjacent normal tissue and 28 benign breast lesions were examined by qRT-PCR for expression of DLC-1.

Results: Expression level of DLC-1 in adjacent normal tissue and benign breast lesion specimens was higher than that in breast carcinoma (P<0.

Clinical significance of axin and β-catenin protein expression in primary hepatocellular carcinomas.

The aim of the present research was to investigate clinicopathologic correlations of immunohistochemically- demonstrated axin (axis inhibition) and β-catenin expression in primary hepatocellular carcinomas (HCCs), in comparison with paraneoplastic, cirrhotic and normal liver tissues. Variation in Axin expression across groups were significant (P < 0.01), correlating with alpha fetoprotein (AFP), HBsAg, cancer plugs in the portal vein, and clinical stage of HCCs(P < 0.

Infrasound exposure induces apoptosis of rat cardiac myocytes by regulating the expression of apoptosis-related proteins.

It has been reported that exposure to infrasound causes cardiac dysfunction. Allowing for the key role of apoptosis in the pathogenesis of cardiovascular diseases, the objective of this study was to investigate the apoptotic effects of infrasound. Cardiac myocytes cultured from neonatal rats were exposed to infrasound of 5 Hz at 130 dB.

AC-NP: a novel chimeric peptide with natriuretic and vasorelaxing actions.

The aim of this study was to evaluate the cardiovascular and renal activities of a newly designed natriuretic peptide (NP). Here, we engineered a novel 28-amino acid chimeric peptide, termed AC-NP that combined the 17-amino acid ring of C type natriuretic peptide (CNP) with the 6-amino acid N-terminus and 5-amino acid C-terminus of atrial natriuretic peptide (ANP). Both in vitro and in vivo experiments were performed to determine the actions of AC-NP.

Protecting effects of vasonatrin peptide against carbon tetrachloride-induced liver fibrosis.

In order to investigate the effects of vasonatrin peptide (VNP), a novel man-made natriuretic peptide, on liver fibrosis, mice received carbon tetrachloride (CCl(4)) injection for 12weeks and with or without VNP treatment during the last 6weeks. Hematoxylin-eosin (HE) staining and Sirius red staining were performed to evaluate the status of liver fibrosis. After treatment of VNP, DNA and collagen synthesis of cultured HSC-T6 hepatic stellate cells were assessed by [(3)H]-thymidine and [(3)H]-proline incorporation, respectively.

Protective effects of vasonatrin peptide against hypobaric hypoxia-induced pulmonary hypertension in rats.

1. The aim of the present study was to investigate the in vivo effects of vasonatrin peptide (VNP) on hypoxia-induced pulmonary hypertension (HPH). 2.

[Randomized controlled multi-central study on acupuncture at Tanzhong (CV 17) for treatment of postpartum hypolactation].

Objective: To study on clinical role of acupuncture at Tanzhong (CV 17) for treatment of postpartum hypolactation and to provide clinical basis for indications of acupoints.

Methods: This was a single blind randomized controlled multi-center study by Beijing obstetrical and gynecological hospital, Beijing Mother and Child health institute and Haidian Mother and Child health institute, 276 cases of postpartum hypolactation were randomly divided into an acupuncture group and a Chinese drug group. The acupuncture group were treated with acupuncture at Tanzhong (CV 17) and the Chinese drug group with traditional drug Tongre Decoction.