The HTLV-I oncoprotein Tax inactivates the tumor suppressor FBXW7.

Unlabelled: Human T-cell leukemia virus type 1 (HTLV-I) is the etiological agent of adult T-cell leukemia (ATL). Mutational analysis has demonstrated that the tumor suppressor, F-box and WD repeat domain containing 7 (FBXW7/FBW7/CDC4), is mutated in primary ATL patients. However, even in the absence of genetic mutations, FBXW7 substrates are stabilized in ATL cells, suggesting additional mechanisms can prevent FBXW7 functions.

Protective Effects of Bariatric Surgery on Kidney Functions by Inhibiting Oxidative Stress Responses Through Activating PPARα in Rats With Diabetes.

Objective: The aim of this study was to explore the protective effects and the regulatory mechanisms of bariatric surgery on kidney injury in diabetic rats.

Methods: We established a useful type 2 diabetic rat model using high-fat and high-sugar diet feeding following low-dose streptozotocin (STZ) treatment. Sprague-Dawley (SD) rats were randomly divided into the following groups: control (Con) group, diabetic nephropathy (DN) group, and duodenal-jejunal bypass (DJB) surgery group.

Germinal epimutation of Fragile Histidine Triad (FHIT) gene is associated with progression to acute and chronic adult T-cell leukemia diseases.

Background: Human T cell Leukemia virus type 1 (HTLV-I) is etiologically linked to adult T cell leukemia/lymphoma (ATL) and an inflammatory neurodegenerative disease called HTLV-I-associated myelopathy or tropical spastic paraparesis (HAM/TSP). The exact genetic or epigenetic events and/or environmental factors that influence the development of ATL, or HAM/TSP diseases are largely unknown. The tumor suppressor gene, Fragile Histidine Triad Diadenosine Triphosphatase (FHIT), is frequently lost in cancer through epigenetic modifications and/or deletion.

Comparative Toxicity of Nanomaterials to Air-blood Barrier Permeability Using an In Vitro Model.

Objective: To comparatively study the toxicity of four metal-containing nanoparticles (MNPs) and their chemical counterparts to the air-blood barrier (ABB) permeability using an in vitro model.

Methods: ABB model, which was developed via the co-culturing of A549 and pulmonary capillary endothelium, was exposed to spherical CuO-NPs (divided into CuO-40, CuO-80, and CuO-100 based on particle size), nano-Al2O3 (sheet and short-rod-shaped), nano-ZnO, nano-PbS, CuSO4, Al2(SO4)3, Zn(CH3COO)2, and Pb(NO3)2 for 60 min. Every 10 min following exposure, the cumulative cleared volume (ΔTCL) of Lucifer yellow by the model was calculated.

NOTCH1 Activation Depletes the Pool of Side Population Stem Cells in ATL.

Background: HTLV-I infection is associated with the development of adult T-cell leukemia (ATL), a malignancy characterized by a high rate of disease relapse and poor survival. Previous studies reported the existence of side population (SP) cells in HTLV-I Tax transgenic mouse models. These studies showed that these ATL-like derived SP cells have both self-renewal and leukemia renewal capacity and represent Cancer Stem Cells (CSC)/Leukemia-Initiating Cells (LIC).

Naturally Existing Oncolytic Virus M1 Is Nonpathogenic for the Nonhuman Primates After Multiple Rounds of Repeated Intravenous Injections.

Cancers figure among the leading causes of morbidity and mortality worldwide. The number of new cases is expected to rise by about 70% over the next 2 decades. Development of novel therapeutic agents is urgently needed for clinical cancer therapy.

Mutation of epigenetic regulators TET2 and MLL3 in patients with HTLV-I-induced acute adult T-cell leukemia.

Background: Epigenetic regulators play a critical role in the maintenance of specific chromatin domains in an active or repressed state. Disruption of epigenetic regulatory mechanisms is widespread in cancer cells and largely contributes to the transformation process through active repression of tumor suppressor genes. While mutations of epigenetic regulators have been reported in various lymphoid malignancies and solid cancers, mutation of these genes in HTLV-I-associated T-cell leukemia has not been investigated.

Small PARP inhibitor PJ-34 induces cell cycle arrest and apoptosis of adult T-cell leukemia cells.

Background: HTLV-I is associated with the development of an aggressive form of lymphocytic leukemia known as adult T-cell leukemia/lymphoma (ATLL). A major obstacle for effective treatment of ATLL resides in the genetic diversity of tumor cells and their ability to acquire resistance to chemotherapy regimens. As a result, most patients relapse and current therapeutic approaches still have limited long-term survival benefits.

miR-28-3p is a cellular restriction factor that inhibits human T cell leukemia virus, type 1 (HTLV-1) replication and virus infection.

Human T cell leukemia virus, type 1 (HTLV-1) replication and spread are controlled by different viral and cellular factors. Although several anti-HIV cellular microRNAs have been described, such a regulation for HTLV-1 has not been reported. In this study, we found that miR-28-3p inhibits HTLV-1 virus expression and its replication by targeting a specific site within the genomic gag/pol viral mRNA.

Tax impairs DNA replication forks and increases DNA breaks in specific oncogenic genome regions.

Background: Human T-cell leukemia virus type 1 (HTLV-I) is a human retrovirus associated with adult T-cell leukemia (ATL), an aggressive CD4 T-cell proliferative disease with dismal prognosis. The long latency preceding the development of the disease and the low incidence suggests that the virus itself is not sufficient for transformation and that genetic defects are required to create a permissive environment for leukemia. In fact, ATL cells are characterized by profound genetic modifications including structural and numerical chromosome alterations.

Overview on HTLV-1 p12, p8, p30, p13: accomplices in persistent infection and viral pathogenesis.

The human T-lymphotropic virus type-1 (HTLV-1) is etiologically linked to adult T cell leukemia/lymphoma and tropical spastic paraparesis/HTLV-1-associated myelopathy. While the role of Tax and Rex in viral replication and pathogenesis has been extensively studied, recent evidence suggests that additional viral proteins are essential for the virus life cycle in vivo. In this review, we will summarize possible molecular mechanisms evoked in the literature to explain how p12, p8, p30, and p13 facilitate persistent viral infection of the host.

PA28γ is a novel corepressor of HTLV-1 replication and controls viral latency.

Unlabelled: The establishment of a latent reservoir by human tumor viruses is a vital step in initiating cellular transformation and represents a major shortcoming to current therapeutic strategies and the ability to eradicate virus-infected cells. Human T-cell leukemia virus type 1 (HTLV-1) establishes a lifelong infection and is linked to adult T-cell leukemia lymphoma (ATLL). Here, we demonstrate that HTLV-1 p30 recruits the cellular proteasome activator PA28γ onto the viral tax/rex mRNA to prevent its nuclear export and suppress virus replication.

HTLV-I tax increases genetic instability by inducing DNA double strand breaks during DNA replication and switching repair to NHEJ.

Background: Appropriate responses to damaged DNA are indispensible for preserving genome stability and preventing cancer. Tumor viruses often target DNA repair machinery to achieve transformation. The Human T-cell leukemia virus type I (HTLV-I) is the only known transforming human retrovirus and the etiological agent of Adult T-cell Leukemia (ATLL).

Association of polymorphisms of STAT6 and SO(2) with Chinese childhood asthma: a case-control study.

Objective: To investigate the association of polymorphisms of STAT6 gene and air pollutants of PM(10), NO(2), and SO(2), with asthma in Chinese children.

Methods: 418 subjects aged 14 years and under were recruited in a case-control study. The association between STAT6 polymorphisms and childhood asthma were tested by allele frequency, genotype analysis, and MDR analysis.

In vivo interstitial migration of primitive macrophages mediated by JNK-matrix metalloproteinase 13 signaling in response to acute injury.

Interstitial cell migration through extracellular matrix is a hallmark of the inflammation response, tumor invasion, and metastasis. We have established a stable zebrafish transgenic line expressing enhanced GFP under the lysozyme C promoter for visualizing and measuring primitive macrophage migration in vivo. We show that tissue-resident primitive macrophages migrate rapidly through extracellular matrix to the site of acute injury induced by tail transection.

The investigation of mutation and single nucleotide polymorphism of receptor tyrosine kinases and downstream scaffold molecules in acute myeloid leukemia.

We investigate the role of mutations of receptor tyrosine kinases as well as their downstream scaffold molecules in leukemogenesis of acute myeloid leukemia (AML) in Chinese patients. Genes of interest included FLT3, PDGFRbeta, KDR, CSF2Rbeta, SOCS1, PIAS3 and SHIP. The coding sequence of these genes was analysed by the reverse transcription-polymerase chain reaction to search novel mutations.

[Study of mutation and single nucleotide polymorphism of PDGFRbeta and SHIP gene in acute myeloid leukemia].

Objective: To investigate the significance of mutation and single nucleotide polymorphism (SNP) of class III receptor tyrosine kinases such as PDGFRbeta and SHIP in acute myeloid leukemia (AML) patients.

Methods: Screening of the mutation and SNP of PDGFRbeta and SHIP by genomic PCR, RT-PCR, directly sequencing and Mass-ARRAY system was carried out in 273 AML patients.

Results: The mutations of PDGFRbeta R685C and SHIP Q1153L were detected for the first time in AML patients.

Trans-repressive effect of NUP98-PMX1 on PMX1-regulated c-FOS gene through recruitment of histone deacetylase 1 by FG repeats.

The formation of fusion genes between NUP98 and members of the HOX family represents a critical factor for the genesis of acute leukemia or acute transformation of chronic myeloid leukemia (CML). To gain insights into the molecular mechanisms underlying the leukemogenesis of NUP98-HOX fusion products, we cloned NUP98-PMX1 from a CML-blast crisis patient with t(1;11) as a secondary chromosomal translocation, and functionally studied the fusion products in detail through various molecular and protein biochemical assays. In addition to many interesting features, we have found that the NUP98-PMX1 fusion protein exerts a repressive effect on PMX1 or serum response factor-mediated c-FOS activation, probably through the recruitment of a common corepressor histone deacetylase 1 by FG domains of the NUP98-PMX1 fusion protein.

[Effect of 900 MHz electromagnetic fields on the expression of GABA receptor of cerebral cortical neurons in postnatal rats].

Objective: To investigate the effects of 900 MHz microwave electromagnetic fields (EMF) on the expression of neurotransmitter GABA receptor of cerebral cortical neurons in postnatal rats.

Methods: Neurons were exposed to 900 MHz continuous microwave EMF (SAR = 1.15 - 3.

[Effect of formaldehyde on energy metabolism in postnatal rat cortex neurons in culture].

Objective: The mechanism of the effect of formaldehyde on CNS which is much concerned to formaldehyde poisoning was studied.

Methods: In the present study, incubation of postnatal rat cortex neurons in culture with formaldehyde at 1, 2, 4, 8 mg/L (medium) was carried out to evaluate the effect of formaldehyde on energy metabolism.

Results: The result of cytochemistry showed a significant down-regulation of cytochrome oxidase activity after consecutive formaldehyde treatment for 4 hours compared with the control (P < 0.

[Effect of 900Mhz electromagnetic fields on energy metabolism in postnatal rat cerebral cortical neurons].

Objective: To study the effect of 900MHz low intensity microwave electromagnetic fields (EMF) on AMPA GluR2 and the concentration of intracellular calcium in postnatal rat cerebral cortical neurons.

Methods: Neurons were exposed to low intensity 900MHz continuous microwaves EMF (SAR = 3.22W/kg, 2.

Association between single nucleotide polymorphisms in deoxycytidine kinase and treatment response among acute myeloid leukaemia patients.

Development of resistance to 1-beta-arabinofuranosylcytosine (AraC) is a major obstacle in the treatment of patients with acute myeloid leukaemia (AML). Deficiency of functional deoxycytidine kinase (dCK) plays an important role in AraC resistance in vitro. We screened 5378 bp sequences of the dCK gene, including all exons and the 5' flanking region, and identified two single nucleotide polymorphisms (SNPs) in the regulatory region (rSNPs) with high allele frequencies.