The non-cell-autonomous function of ID1 promotes AML progression via ANGPTL7 from the microenvironment.

The bone marrow microenvironment (BMM) can regulate leukemia stem cells (LSCs) via secreted factors. Increasing evidence suggests that dissecting the mechanisms by which the BMM maintains LSCs may lead to the development of effective therapies for the eradication of leukemia. Inhibitor of DNA binding 1 (ID1), a key transcriptional regulator in LSCs, previously identified by us, controls cytokine production in the BMM, but the role of ID1 in acute myeloid leukemia (AML) BMM remains obscure. Here, we report that ID1 is highly expressed in the BMM of patients with AML, especially in BM mesenchymal stem cells, and that the high expression of ID1 in the AML BMM is induced by BMP6, secreted from AML cells. Knocking out ID1 in mesenchymal cells significantly suppresses the proliferation of cocultured AML cells. Loss of Id1 in the BMM results in impaired AML progression in AML mouse models. Mechanistically, we found that Id1 deficiency significantly reduces SP1 protein levels in mesenchymal cells cocultured with AML cells. Using ID1-interactome analysis, we found that ID1 interacts with RNF4, an E3 ubiquitin ligase, and causes a decrease in SP1 ubiquitination. Disrupting the ID1-RNF4 interaction via truncation in mesenchymal cells significantly reduces SP1 protein levels and delays AML cell proliferation. We identify that the target of Sp1, Angptl7, is the primary differentially expression protein factor in Id1-deficient BM supernatant fluid to regulate AML progression in mice. Our study highlights the critical role of ID1 in the AML BMM and aids the development of therapeutic strategies for AML.

The correlation between miR -34a-3p, miR -31, PLEK2 and the occurrence, development and prognosis of colorectal cancer.

The current study aimed to explore the correlation between Mir-34A-3p, Mir-31, PLEK2 and the occurrence, development and prognosis of colorectal cancer. For this paper, 120 patients with colorectal cancer were selected as the study group, and their adjacent normal tissues were selected as the control group. The quantitative real-time PCR (QRT-PCR) method was used to detect miR-34a-3p and miR-31 in tissues, and the immunohistochemistry EnVision two-step method was used to detect PLEK2 positive expression. The expressions of miR -34a-3p, miR -31, and PLEK2 in colon cancer tissues and normal cancer tissues were compared, and the correlation between miR -34a-3p, miR -31, and PLEK2 and clinic-pathological characteristics of colorectal cancer patients were analyzed. The results showed that expression of miR -34a-3p, miR -31 and positive expression rate of PLEK2 in colorectal cancer tissues were higher than those in normal adjacent tissues (P<0.05). The expression of miR -34a-3p was related to tumor size, degree of tissue differentiation, lymph node metastasis and TNM stage (P < 0.05). The 3-year survival rate of miR -34a-3p with low expression was lower than miR -34a-3p with high expression, which was a protective factor affecting the poor prognosis of colorectal cancer (P < 0.05). The expression of miR -31 was related to tumor size and TNM stage. The 3-year survival rate of the group with high expression of miR -31 was lower than the group with low expression of miR -31, which was a risk factor affecting the poor prognosis of colorectal cancer (P < 0.05). PLEK2 positive expression was associated with lymph node metastasis, and the 3-year survival rate of the PLEK2 positive group was lower than the PLEK2 low expression group, which was a risk factor for poor prognosis of colorectal cancer (P < 0.05). In general, miR -34a-3p, miR -31, and PLEK2 are closely associated with the occurrence and development of colorectal cancer, and they are all influential factors affecting the prognosis of patients with colorectal cancer, which can provide a basis for the evaluation and treatment of patients, and are worthy of widespread clinical application.

Inhibition of microRNA-103a inhibits the activation of astrocytes in hippocampus tissues and improves the pathological injury of neurons of epilepsy rats by regulating BDNF.

Background: The aim of this study is to explore the effect of microRNA-103a (miR-103a) on astrocytes activation and hippocampal neuron injury in epilepsy rats by targeting brain-derived neurotrophic factor (BDNF). Methods: The epilepsy rat model was induced by intraperitoneal injection of lithium chloride-pilocarpine. Successful modeled rats were intralateroventricularly microinjected with miR-103a inhibitors, inhibitors negative control (NC), siRNA-NC and BDNF-siRNA, respectively. The RT-qPCR and western blot analysis were used to detect the expression of miR-103a, BDNF and glial fibrillary acidic protein (GFAP) in hippocampus tissues of rats. TUNEL staining was used to detect the apoptosis of hippocampal neurons. The RT-PCR and ELISA was used to detect the levels of TNF-α and IL-6 in hippocampal tissues and in serum, respectively. Results: Increased expression of miR-103a, GFAP, and number of apoptotic neurons, decreased expression of BDNF and number of surviving neurons were found in hippocampus tissues of epilepsy rats. After miR-103a inhibitors interfered with epilepsy rats, there showed decreased expression of miR-103a and GFAP, increased expression of BDNF and decreased number of apoptotic neuron as well as increased number of surviving neurons. Compared with miR-103a inhibitors alone, epilepsy rats treated with BDNF-siRNA combined with miR-103a inhibitors significantly increased expression of GFAP in hippocampal tissues of epilepsy rats, increased number of apoptotic neurons and significantly decreased the number of surviving neurons. Conclusion: Our study provides evidence that the inhibition of miR-103a can inhibit the activation of astrocytes in hippocampus tissues and improve the pathological injury of neurons of epilepsy rats by regulating BDNF gene.

Effect of Huqian Wan on liver-Yin and kidney-Yin deficiency patterns in patients with knee osteoarthritis.

OBJECTIVE: To observe the curative effect of Huqian Wan on liver and kidney-Yin deficiency knee osteoarthritis (KOA). METHODS: One hundred patients were randomly divided, into a treatment (50 patients) and control group (50 patients). In the treatment group, patients orally took the Chinese medicine Huqian Wan. Control group patients orally took Votalin, 75 mg, once a day, for 8 weeks. The visual analog scale (VAS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and Medical Outcomes Study Short Form 36-Item Health Survey (SF 36) were used to evaluate the curative effect before treatment and after 8 and 16 weeks of treatment. RESULTS: VAS and WOMAC scores significantly decreased and SF 36 scores significantly increased after treatment in both groups compared with before treatment (P < 0.05). There were significant differences in VAS, WOMAC, and SF 36 score changes between the two groups at week 16 (P < 0.05). There was a significant increase in VAS and WOMAC scores in the control groups (P < 0.05) between weeks 8 and 16, but no significant difference was found in the treatment group (P > 0.05). CONCLUSION: Huqian Wan could effectively improve the clinical symptoms and quality of life in patients with KOA. It could also have a better and longer lasting curative effect without obvious adverse events compared with Votalin.

Acetylation of p53 in the Cerebral Cortex after Photothrombotic Stroke.

p53 expression and acetylation are crucial for the survival and death of neurons in penumbra. At the same time, the outcome of ischemia for penumbra cells depends largely on the histone acetylation status, but the effect of histone acetyltransferases and deacetylases on non-histone proteins like p53 is largely understudied. With combined in silico and in vitro approach, we have identified enzymes capable of acetylation/deacetylation, distribution, stability, and pro-apoptotic activity of p53 in ischemic penumbra in the course of post-stroke recovery, and also detected involved loci of acetylation in p53. The dynamic regulation of the acetylation of p53 at lysine 320 is controlled by acetyltransferase PCAF and histone deacetylases HDAC1 and HDAC6. The in silico simulation have made it possible to suggest the acetylation of p53 at lysine 320 acetylation may facilitate the shuttling of p53 between the nucleus and cytoplasm in penumbra neurons. Acetylation of p53 at lysine 320 is more preferable than acetylation at lysine 373 and probably promotes survival and repair of penumbra neurons after stroke. Strategies to increase p53 acetylation at lysine 320 via increasing PCAF activity, inhibiting HDAC1 or HDAC6, inhibiting p53, or a combination of these interventions may have therapeutic benefits for stroke recovery and would be promising for neuroprotective therapy of stroke.

Inhibition of USP1 reverses the chemotherapy resistance through destabilization of MAX in the relapsed/refractory B-cell lymphoma.

The patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL) have poor prognosis, and a novel and effective therapeutic strategy for these patients is urgently needed. Although ubiquitin-specific protease 1 (USP1) plays a key role in cancer, the carcinogenic effect of USP1 in B-cell lymphoma remains elusive. Here we found that USP1 is highly expressed in DLBCL patients, and high expression of USP1 predicts poor prognosis. Knocking down USP1 or a specific inhibitor of USP1, pimozide, induced cell growth inhibition, cell cycle arrest and autophagy in DLBCL cells. Targeting USP1 by shRNA or pimozide significantly reduced tumor burden of a mouse model established with engraftment of rituximab/chemotherapy resistant DLBCL cells. Pimozide significantly retarded the growth of lymphoma in a DLBCL patient-derived xenograft (PDX) model. USP1 directly interacted with MAX, a MYC binding protein, and maintained the stability of MAX through deubiquitination, which promoted the transcription of MYC target genes. Moreover, pimozide showed a synergetic effect with etoposide, a chemotherapy drug, in cell and mouse models of rituximab/chemotherapy resistant DLBCL. Our study highlights the critical role of USP1 in the rituximab/chemotherapy resistance of DLBCL through deubiquitylating MAX, and provides a novel therapeutic strategy for rituximab/chemotherapy resistant DLBCL.

ROBO1 deficiency impairs HSPC homeostasis and erythropoiesis via CDC42 and predicts poor prognosis in MDS.

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic neoplasms originating from hematopoietic stem progenitor cells (HSPCs). We previously identified frequent roundabout guidance receptor 1 (ROBO1) mutations in patients with MDS, while the exact role of ROBO1 in hematopoiesis remains poorly delineated. Here, we report that ROBO1 deficiency confers MDS-like disease with anemia and multilineage dysplasia in mice and predicts poor prognosis in patients with MDS. More specifically, Robo1 deficiency impairs HSPC homeostasis and disrupts HSPC pool, especially the reduction of megakaryocyte erythroid progenitors, which causes a blockage in the early stages of erythropoiesis in mice. Mechanistically, transcriptional profiling indicates that Cdc42, a member of the Rho-guanosine triphosphatase family, acts as a downstream target gene for Robo1 in HSPCs. Overexpression of Cdc42 partially restores the self-renewal and erythropoiesis of HSPCs in Robo1-deficient mice. Collectively, our result implicates the essential role of ROBO1 in maintaining HSPC homeostasis and erythropoiesis via CDC42.

TRANSCRIPTIONAL ANALYSIS OF ZINC-DEPENDENT HISTONE DEACETYLASES IN SEVERAL HUMAN CANCER CELLS.

Histone deacetylases, especially zinc-dependent deacetylases HDACs, are among attractive drug targets for treating cancer in recent years. AIM: To explore the expression level of HDACs in several human cancer cell lines and examine the possible association between their expression and the sensitivity/resistance to the selective- or pan-HDAC inhibitors. MATERIALS AND METHODS: The RNA expression of 11 HDACs isoforms was assayed in HeLa, HepG2, AV3, HEK293, A549, and K562 cells by semiquantitative reverse transcription-polymerase chain reaction. The sensitivity/resistance of these cell lines to the pan- or selective- HDAC inhibitors was estimated by MTS assay. RESULTS: The relative transcription of HDACs genes demonstrated that members of Class I HDAC (HDAC1, 2 and 3) and members of Class II HDAC (HDAC4, 5, 6 and 7) had slight to significant levels of expression in cell lines under study with no dominant HDAC-subtype gene transcription. pan-HDAC inhibitor demonstrated superior antitumor activity compared to HDAC isoform-selective inhibitor. CONCLUSION: The absence of the dominant HDAC-subtype gene transcription in different human cancer cell lines explains the inferior efficacy of HDAC isoform-selective inhibitors as compared to pan-HDAC inhibitors.

[A study of brain inner tissue water molecule self-diffusion model based on Monte Carlo simulation].

The study of water molecule self-diffusion process is of importance not only for getting anatomical information of brain inner tissue, but also for shedding light on the diffusion process of some medicine in brain tissue. In this paper, we summarized the self-diffusion model of water molecule in brain inner tissue, and calculated the self-diffusion coefficient based on Monte Carlo simulation under different conditions. The comparison between this result and that of Latour model showed that the two self-diffusion coefficients were getting closer when the diffusion time became longer, and that the Latour model was a long time-depended self-diffusion model.

Isolation and Identification of a Murine Norovirus Persistent Infection Strain in China.

Murine Norovirus (MNV) is one of the most known viruses among viruses in mice. Because of the high prevalence of MNV in frequently used laboratory animals in biomedical researches, there is a significant impact of MNV. There may be different prevalence degrees and molecular characteristics of MNV in different regions around the world. Here, we reported an MNV strain "designated HBTS-1806" isolation from commercial mice's feces that caused a detectable cytopathic effect (CPE) in RAW264.7 cells. According to electron microscopy, the virus was 50-70 nm in diameter. The complete genome of HBTS-1806 is 7383 nucleotides with a structure similar to that of MNV reference strains. According to phylogenetic analysis on the basis of the whole genome, HBTS-1806 shared nucleotide sequence identities of 90.2-95.4% with other Chinese isolates reported. Analysis of amino acid sequence on the basis of ORF1 and ORF2 suggested that the isolated strain may be derived from recombination. Although no gross lesions or histopathological changes were found from mice infected with 5 × 105 TCLD50 of MNV by oral gavage inoculation, the intestinal virus loads lasted 12 weeks, suggesting a persistent infection strain of MNV isolate in China.

[Stable isotopes of zooplankton and their applications in the research of aquatic ecosystems]. / æµ®æ¸¸åŠ¨ç‰©ç¨³å®šç¢³ã€æ°®åŒä½ç´ ç‰¹å¾åŠå ¶åœ¨æ°´ç”Ÿæ€ç³»ç»Ÿç ”ç©¶ä¸­çš„åº”ç”¨.

Zooplankton plays a mediating role in the food web of aquatic ecosystems, the stable carbon and nitrogen isotopes (δ13C and δ15N) of which have been widely used to study the utilization of food resources, material cycling pathways, and trophic relationships. The δ13C and δ15N values of zooplankton have been used to predict primary productivity, sources and sinks of pollutants and environmental changes. To better use δ13C and δ15N of zooplankton as ecological and environmental indicators, it is particularly important to understand their temporal and spatial variations and the influencing factors. Based on related literature, we synthesized spatial and temporal variations in δ13C and δ15N of zooplankton in different aquatic ecosystems and taxa groups, and the use of δ13C and δ15N indicators for ecological processes and environmental changes. The δ13C and δ15N of zooplankton are largely affected by its food sources, and its stable isotope compositions are in turn affected by primary productivity and nitrogen sources. We proposed that the combination of δ13C and δ15N in zooplankton with transportation and transformation of emerging pollutants would form a multi-means, multi-disciplinary and multi-scale research direction in the fields of earth science and biology.

[Decalcified freeze-dried bone allograft combined with rich platelet derivatives for the treatment of human periodontal intrabony defects: a Meta-analysis].

OBJECTIVE: This review aims to systematically evaluate the effect of decalcified freeze-dried bone allograft (DFDBA) combined with rich platelet derivatives on the treatment of human periodontal intrabony defects. METHODS: A search in PubMed, Web of Science, Embase, Cochrane Library, CNKI, and other electronic databases was conducted to identify randomized controlled trials (RCT) of the use of DFDBA combined with rich platelet derivatives in the treatment of human periodontal intrabony defects, performed before May 2016. The quality of the RCTs was assessed. RevMan 5.3 software was applied for Meta-analysis. RESULTS: A total of nine RCTs were included. A total of 194 patients and 303 defects were involved. Short-term (6 months) and long-term (12 to 18 months) groups were included. Meta-analysis results revealed that DFDBA combined with rich platelet derivatives was superior to DFDBA or rich platelet derivatives alone for probing depth reduction in the short-term [MD=0.75 mm, 95% confidence intervals (CI) (0.31 mm, 1.20 mm), P=0.001 0] and longterm groups [MD=0.87 mm, 95%CI (0.02 mm, 1.72 mm), P=0.04], clinical attachment level gain in the short-term [MD=
0.65 mm, 95%CI (0.08 mm, 1.22 mm), P=0.03] and long-term groups [MD=1.31 mm, 95%CI (0.60 mm, 2.01 mm), P<0.000 3], gingival recession reduction in the long-term group [MD=-0.58 mm, 95%CI (-0.78 mm, -0.38mm), P<0.000 01], bone fill gain in the short-term [MD=0.52 mm, 95%CI (0.03 mm, 1.00 mm), P=0.04] and long-term groups [MD=1.26 mm, 95%CI (0.65 mm, 1.86 mm), P<0.000 1]. CONCLUSIONS: DFDBA combined with platelet rich derivatives is probably effective in the treatment of human periodontal intrabony defects. It is probably superior to DFDBA or platelet rich derivatives alone. Considering the limitation of the included studies, high-quality and large-sample RCTs are required to evaluate the effect.

[Medical image segmentation techniques].

Medical image segmentation is an important application of image segmentation. However it is the bottleneck that restrains medical image application in clinical practice. In this paper, the aim and significance of medical image segmentation are discussed, the development of medical image segmentation techniques is sketched, and a review of the medical image segmentation techniques is given.

Antilipolytic actions of vanadate and insulin in rat adipocytes mediated by distinctly different mechanisms.

Vanadate, which mimics the biological effects of insulin, also inhibits lipolysis in rat adipocytes. Here we demonstrate that the antilipolytic effect of vanadate differs from that of insulin at least by the five following criteria: 1) vanadate inhibits lipolysis mediated by high (supraphysiological) concentrations of catecholamines; 2) vanadate antagonizes (Bu)2cAMP-mediated lipolysis; 3) vanadate antagonizes isobutylmethylxanthine-dependent lipolysis, 4) vanadate inhibits lipolysis mediated by okadaic acid; and 5) wortmannin, which blocks the antilipolytic effect of insulin, fails to block vanadate-mediated antilipolysis. Vanadate does activate phosphoinositol 3-kinase, and wortmannin blocks this activation. Our working hypothesis assumes that all of the insulin-like effects of vanadate, including antilipolysis, are initiated by the inhibition of protein phosphotyrosine phosphatases (PTPases). Among documented PTPase inhibitors we found that VOSO4 (oxidation state +4), several organic vanadyl compounds (+4), zinc (Zn2+), tungstate (W), and molybdate (Mo) also had antilipolytic activity. The order of potency was vanadyl acetylacetonate > or = VOSO4 > or = NaVO3 > or = vanadyl-dipicolinate > Zn2+ >> W > Mo, and it correlated better with the inhibition of adipose membranal-PTPases in cell-free experiments. We have concluded that the antilipolytic effect of vanadate is 1) mechanistically distinct from that of insulin, 2) independent of phosphoinositol 3-kinase activation, and 3) independent of the lipolytic cascade. We also strongly suggest that the antilipolytic effect of vanadate emanates from inhibiting adipose membranal, rather than cytosolic PTPases, and present preliminary data showing distinct differences in catalysis between these two PTPase categories. Overall, the study indicates that antilipolysis can be manifested via alternative, insulin-independent, signal-transducing pathways.

The treatment of radioactive wastewater by ultrasonic standing wave method.

The radiation hazards of radionuclide arising from the storage of nuclear weapons cannot be ignored to the operators. Ultrasonic standing wave methods can be considered as the green cleaning separation techniques with high efficiency. The application of ultrasonic standing wave methods for liquid radioactive wastes treatment requires solving many problems connected with the proper selection of the frequency and power of ultrasonic transducers, and the processing time, etc. Based on the model of one single suspended radioactive particle subjected to in the field of ultrasonic standing wave, the principle of the treatment of low-level radioactive wastewater by ultrasound was analyzed. The theoretical and simulation results show that under the action of ultrasonic standing wave, the particle will move toward the wave node plane, and the time of particle reaching the plane become shorter when the radius of particle and the frequency and power of ultrasound was enlarged. The experimental results show that the radioactive concentration of wastewater could be reduced from 400 Bq L(-1) to 9.3 Bq L(-1) and the decontamination efficiency was 97.68%. The decontamination efficiency could not be obviously improved by further increasing the treating time.

A novel assay for evaluating glycogenolysis in rat adipocytes and the inability of insulin to antagonize glycogenolysis in this cell type.

We report here on a novel procedure for measuring glycogenolysis in rat adipocytes. In this procedure, cells are incubated for 30 min at 37 degrees C with insulin or vanadate, and with [U-14C]glucose to label the glycogen pool with radioactive glucose. The cells are washed and preincubated for an additional 1 h, before being assayed. The extent of glycogenolysis is determined by the decrease in radioactivity in precipitated glycogen, which was quite substantial under experimental conditions facilitating glycogenolysis. From the assay, we determined the following. (a) Glycogenolysis is activated in rat adipocytes in response to lipolytic hormones (i.e. catecholamines and adrenocorticotropic hormone). (b) Other agents and conditions elevating intracellular adenosine 3',5'-monophosphate levels (i.e. cholera toxin, dibutyryladenosine 3',5'-monophosphate, and isobutylmethylxanthine) also activate glycogenolysis. (c) Glycogenolysis (as opposed to lipolysis) is activated at concentrations of adrenocorticotropic hormone or isoproterenol 7-11-fold lower and at adenosine 3',5'-monophosphate concentrations 7-fold lower. (d) Calyculin A, a specific inhibitor of protein phosphatase 1, activates glycogenolysis as well. Calyculin A also activates lipolysis at an equimolar potency. (e) Insulin does not antagonize glycogenolysis in rat adipocytes. In conclusion, the assay allowed us to compare glycogenolysis to lipolysis within the same cell, and to find that the sensitivity to hormones and adenosine 3',5'-monophosphate was about 1 order of magnitude higher for glycogenolysis than for lipolysis. A more striking finding was the inability of insulin to antagonize glycogenolysis in the rat adipose cell, an effect which occurs readily in liver and muscle cells via protein phosphatase 1-activating machinery. This rules out a role for adipose protein phosphatase 1 activation in the mechanism by which insulin antagonizes lipolysis and supports the contention that the insulin effect in lowering adenosine 3',5'-monophosphate levels is the central mechanism by which insulin antagonizes lipolysis.