Somatic mutations of isocitrate dehydrogenase 1 (IDH1) at R132 are frequently found in certain cancers such as glioma. With losing the activity wild-type IDH1, R132H and R132C mutant proteins can reduce α-ketoglutaric acid (α-KG) to d-2-hydroxyglutaric (D2HG). The resulting high concentration D2HG inhibits many α-KG-dependent dioxygenases, including histone demethylases, cause broad hypermethylation. These aberrant epigenetic changes responsible for initiation these cancers. We report...

Abstract SAMHD 1 possesses multiple functions, but whether cellular factors regulate expression or its function remains not well characterized. Here, by investigating why cultured RD and HEK 293T cells show different sensitivity to enterovirus 71 (EV71) infection, we demonstrate that is a restriction factor for EV71. Importantly, identify TRIM 21, an E3 ubiquitin ligase, as key regulator of 1, which specifically interacts degrades through the proteasomal pathway. However, 21 has no effect on...

Human enterovirus (EV) pathogens cause various contagious diseases such as hand, foot, and mouth disease, encephalitis, myocarditis, acute flaccid myelitis, pneumonia, bronchiolitis, which have become serious health threats. However, except for the EV71 vaccine on market, there are no effective strategies to prevent treat other EV pathogen infections. Therefore, broad-spectrum anti-EV drugs urgently needed. In this study, we demonstrated that FNC, a small nucleoside analog inhibitor has been...

Mutations in isocitrate dehydrogenase (IDH), a key enzyme the tricarboxylic acid cycle, have recently been found ~75% glioma and ~20% acute myeloid leukemia. Different from wild-type enzyme, mutant IDH1 catalyzes reduction of α-ketoglutaric to D-2-hydroxyglutaric acid. Strong evidence has shown represents novel target for this type cancer. We two 1-hydroxypyridin-2-one compounds that are potent inhibitors R132H R132C mutants with Ki values as low 120 nM. These exhibit >60-fold selectivity...

1-Deoxy-d-xylulose-5-phosphate reductoisomerase (DXR) in the nonmevalonate isoprene biosynthesis pathway is a target for developing antimalarial drugs. Fosmidomycin, potent DXR inhibitor, showed safety as well efficacy against Plasmodium falciparum malaria clinical trials. On basis of our previous quantitative structure–activity relationship (QSAR) and crystallographic studies, several novel pyridine-containing fosmidomycin derivatives were designed, synthesized, found to be highly...

Enterovirus 68 (EVD68) causes respiratory illness, mostly in children. Despite a reported low-level of transmission, the occurrence several recent outbreaks worldwide including 2014 outbreak North America has raised concerns regarding pathogenesis and evolution EVD68. To elucidate phylogenetic features EVD68 possible for outbreak, 216 strain sequences were retrieved from Genbank, 22 outbreak. Several geographic genotypic origins established these strains, 19 which classified as Clade B. Of...

Mutations of isocitrate dehydrogenase 1 (IDH1) are frequently found in certain cancers such as glioma. Different from the wild-type (WT) IDH1, mutant enzymes catalyze reduction α-ketoglutaric acid to d-2-hydroxyglutaric (D2HG), leading cancer initiation. Several 1-hydroxypyridin-2-one compounds were identified be inhibitors IDH1(R132H). A total 61 derivatives synthesized, and their structure–activity relationships investigated. Potent IDH1(R132H) with Ki values low 140 nM, while they possess...

Recent epidemiological data indicate that outbreaks of hand, foot, and mouth disease (HFMD), which can be categorized according to its clinical symptoms as typical or atypical, have markedly increased worldwide. A primary causative agent for HFMD outbreaks, enterovirus 71 (EV71), has been shown manipulate the cell cycle in S phase own replication; however, it is not clear whether coxsackievirus (CVA6), main atypical HFMD, also regulates host cycle. In this study, we demonstrate first time...

Although the host restriction factor APOBEC3G (A3G) has broad spectrum antiviral activity, whether A3G inhibits enterovirus 71 (EV71) been unclear until now. In this study, we demonstrated for first time that could inhibit EV71 virus replication. Silencing in H9 cells enhanced replication, and replication was lower expressing than Jurkat without expression, indicating inhibition A3G-specific. Further investigation revealed inhibited 5'UTR activity of by competitively binding to through its...

The NF-κB pathway plays key roles in HIV-1 replication and reactivation of latency. A regulator inhibiting activation may be a promising therapeutic strategy against HIV-1. Recently, NF-κB-interacting long noncoding RNA (NKILA) was identified to suppress the development different human cancers by IκB kinase (IKK)-induced phosphorylation activation, whereas relationship between NKILA is still unknown. Here, our results show that inhibits suppressing terminal repeat (LTR)-driven transcription...

ABSTRACT Platelet factor 4 (PF4) has been shown to regulate several viral infections. Our previous study demonstrated that PF4 inhibits the entry of enterovirus A 71 (EV71) and coxsackievirus A16 (CA16), which cause hand, foot, mouth disease (HFMD). In this study, we report also circulating HFMD pathogen A6 (CA6) re-emerging D68 (EVD68). 15-amino acid peptide, C15, at C-terminus confers anti-viral activity against multiple enteroviruses (EVs) besides CA6 EVD68, including EV71 CA16....

ABSTRACT Coxsackievirus A6 (CV-A6) is an emerging pathogen associated with hand, foot, and mouth disease (HFMD). Its genetic characterization pathogenic properties are largely unknown. Here, we report 39 circulating CV-A6 strains isolated in 2013 from HFMD patients northeast China. Three major clusters of were identified related to CV-A6, mostly Shanghai, indicating that domestic responsible for Four full-length genomes representing each cluster sequenced analyzed further. Bootscanning tests...

The global spread of enteroviruses (EVs) has become more frequent, severe and life-threatening. Intereron (IFN) I been proved to control EVs by regulating IFN-stimulated genes (ISG) expression. 2'-5'-oligoadenylate synthetases 3 (OAS3) is an important ISG in the OAS/RNase L antiviral system. relationship between OAS3 still unclear. Here, we reveal that OAS3, superior OAS1 OAS2, significantly inhibited EV71 replication vitro. However, utilized autologous 3C protease (3Cpro) cleave...

We cloned the gene ACM61449 from anaerobic, thermophilic Caldicellulosiruptor bescii, and expressed it in Escherichia coli origami (DE3). After purification through thermal treatment Ni-NTA agarose column extraction, we characterized properties of recombinant protein (CbPelA). The optimal temperature pH were 72 °C 5.2, respectively. CbPelA demonstrated high thermal-stability, with a half-life 14 h at 70 °C. also showed very activity for polygalacturonic acid (PGA), released monogalacturonic...

It has been demonstrated that microRNA-497 (miR-497) acts as a tumor suppressor and is involved in progression, development metastasis several types of cancer. However, little known about the exact role miR-497 osteosarcoma (OS). The aim current study was to investigate potential human OS. growth survival OS cells determined using vitro approaches nude mouse model. results exogenous expression MG63 suppressed cell proliferation, colony formation, migration invasion, induced apoptosis arrest...

Serine incorporator 3 (SERINC3) and SERINC5 were recently identified as host intrinsic factors against human immunodeficiency virus (HIV)-1 counteracted by HIV-1 Nef. However, whether they inhibit hepatitis B (HBV), which is a severe health problem worldwide, unknown. Here, we demonstrate that potently inhibited HBV virion secretion in the supernatant without affecting intracellular core particle-associated DNA total RNA, but SERINC3 SERINC1 did not. Further investigation discovered...

A novel thermophilic bacterial strain, CBS-Z T , was isolated from a terrestrial hot spring in the Changbai Mountains, PR China. Cells of strain were short straight rods without flagella and had Gram-positive cell walls. Growth observed at 40–90 °C (optimum 75 °C) pH 5.6–8.6 7.8). The primary end-products fermentation filter paper by acetate, lactate, H 2 CO . main cellular fatty acids iso-C 17 : 0 14 3-OH C 16 G+C content genomic DNA 36.08 mol%. Multiple sequence alignment 16S rRNA gene...

Abstract Background: Radiation (IR)-induced DNA damage triggers cell cycle arrest and has a suppressive effect on the tumor microenvironment (TME). Wee1, regulator, can eliminate G2/M by phosphorylating cyclin-dependent kinase 1 (CDK1). Meanwhile, programed death-1/programed death ligand-1 (PD-1/PDL-1) blockade is closely related to TME. This study aims investigate effects mechanisms of Wee1 inhibitor AZD1775 anti-PD-1 antibody (anti-PD-1 Ab) radiosensitization hepatoma. Methods: The...

A bioinformatic screening of the genome thermophilic bacterium Fervidobacterium nodosum Rt17-B1 for esterhydrolyzing enzymes revealed a putative bacterial esterase (FNE) encoded by Fond_1301 with typical GDSL family motifs. To confirm its function, FNE gene was cloned, functionally expressed in Escherichia coli, and purified to homogeneity. Recombinant exhibited highest activity 14,000 U/mg p-nitrophenyl acetate (pNPC(2)) as substrate. The catalytic efficiency (k(cat)/K(m)) toward (C(2))...