[Research progress on prevention and local intervention of oral mucositis in patients with hematopoietic stem cell transplantation].

Oral mucositis (OM) is a common complication during hematopoietic stem cell transplantation. When OM occurs, with the destruction of oral mucosal barrier function, the formation of oral bacterial environment is accelerated, which has a negative impact on the life quality and clinical outcomes of patients. OM can be prevented by keeping the oral cavity clean, using the mouthwash properly, and limiting the delivery of cytotoxic drugs to oral tissues. This review describes the research progress on the prevention and local intervention of OM in patients with hematopoietic stem cell transplantation, in order to provide ideas for the selection of clinical intervention and management strategies on OM, and to provide references for exploring effective management methods for OM.

Tet1 Isoforms Differentially Regulate Gene Expression, Synaptic Transmission, and Memory in the Mammalian Brain.

The dynamic regulation of DNA methylation in postmitotic neurons is necessary for memory formation and other adaptive behaviors. Ten-eleven translocation 1 (TET1) plays a part in these processes by oxidizing 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), thereby initiating active DNA demethylation. However, attempts to pinpoint its exact role in the nervous system have been hindered by contradictory findings, perhaps due in part, to a recent discovery that two isoforms of the Tet1 gene are differentially expressed from early development into adulthood. Here, we demonstrate that both the shorter transcript (Tet1S ) encoding an N-terminally truncated TET1 protein and a full-length Tet1 (Tet1FL ) transcript encoding canonical TET1 are co-expressed in the adult mouse brain. We show that Tet1S is the predominantly expressed isoform and is highly enriched in neurons, whereas Tet1FL is generally expressed at lower levels and more abundant in glia, suggesting their roles are at least partially cell type-specific. Using viral-mediated, isoform and neuron-specific molecular tools, we find that the individual repression of each transcript leads to the dysregulation of unique gene ensembles and contrasting changes in basal synaptic transmission. In addition, Tet1S repression enhances, while Tet1FL impairs, hippocampal-dependent memory in male mice. Together, our findings demonstrate that each Tet1 isoform serves a distinct role in the mammalian brain.SIGNIFICANCE STATEMENT In the brain, activity-dependent changes in gene expression are required for the formation of long-term memories. DNA methylation plays an essential role in orchestrating these learning-induced transcriptional programs by influencing chromatin accessibility and transcription factor binding. Once thought of as a stable epigenetic mark, DNA methylation is now known to be impermanent and dynamically regulated, driving neuroplasticity in the brain. We found that Tet1, a member of the ten-eleven translocation (TET) family of enzymes that mediates removal of DNA methyl marks, is expressed as two separate isoforms in the adult mouse brain and that each differentially regulates gene expression, synaptic transmission and memory formation. Together, our findings demonstrate that each Tet1 isoform serves a distinct role in the CNS.

MiR-155 promotes proliferation and inhibits apoptosis of nasopharyngeal carcinoma cells through targeting PTEN-PI3K/AKT pathway.

OBJECTIVE: Nasopharyngeal carcinoma (NPC) is a polygenic hereditary disease, and the exact pathogenesis remains poorly understood. MiR-155 regulates the development and progression of several tumors. However, the role of MiR-155 in NPC has not been elucidated. PATIENTS AND METHODS: The NPC cell line CNE2 was cultured in vitro and divided into control group, miR-155 mimics group, and miR-155 inhibitor group, followed by analysis of miR-155 expression by real-time PCR, cell proliferation by MTT assay, cell invasion by transwell chamber, Caspase3 activity, apoptosis of CNE2 cells by flow cytometry, and the expression of PTEN-PI3K/AKT signaling pathway by Western blot. RESULTS: Transfection of miR-155 mimics significantly up-regulated miR-155 expression, promoted the proliferation and invasion of CNE2 cells, inhibited Caspase 3 activity, and decreased cell apoptosis, and PTEN expression, as well as increased PI3K/AKT phosphorylation, compared with control group (p < 0.05). Transfection of miR-155 inhibitor inhibited the proliferation and invasion of CNE2 cells, increased Caspase 3 activity, cell apoptosis, and PTEN expression, as well as reduced PI3K/AKT phosphorylation. Compared with control group, the differences were statistically significant (p < 0.05). CONCLUSIONS: Up-regulation of miR-155 can promote the proliferation of NPC cells and inhibit cell apoptosis by targeting the PTEN-PI3K/AKT pathway, thereby participating in the development and invasion of NPC, indicating that it might be a potential novel target for treating NPC.

The beneficial impact of missing KIR ligands and absence of donor KIR2DS3 gene on outcome following unrelated hematopoietic SCT for myeloid leukemia in the Chinese population.

The effect of natural killer (NK) cell alloreactivity on the outcome of unrelated hematopoietic SCT (HSCT) remains a topic of debate. NK cell alloreactivity after allogeneic HSCT is regulated by killer-cell Ig-like receptors (KIRs). To investigate the influence of KIRs on outcome after unrelated HSCT, we retrospectively analyzed the HLA and KIR genotypes of 116 donor-recipient pairs. We found that missing KIR ligands in recipients were significantly associated with a decreased leukemic relapse risk (P=0.019, HR=0.329), mainly in myeloid disease (P=0.003, HR=0.193). This beneficial effect was seen in AML/myelodysplastic syndrome and also in chronic myeloid leukemia. In myeloid disease, missing KIR ligands also improved 5-year OS (P=0.034, HR=0.430) and disease-free survival (DFS) (P=0.024, HR=0.445). Meanwhile, the presence of donor-activating KIR2DS3 gene was associated with increased relapse risk (P=0.003, HR=5.046), decreased OS (P=0.004, HR=3.181) and DFS (P=0.003, HR=2.919) in myeloid disease. No effect was seen in patients with lymphoid disease. Our study indicated that, in unrelated HSCT for myeloid leukemia, missing KIR ligands in recipients offered a lower relapse risk and a long-term survival advantage. The presence of KIR2DS3 in the donor was an important risk factor for myeloid leukemia.

Magnetic resonance molecular imaging of post-stroke neuroinflammation with a P-selectin targeted iron oxide nanoparticle.

We have developed a magnetic resonance molecular imaging method using a novel iron-oxide contrast agent targeted towards P-selectin - MNP-PBP (magnetic nanoparticle-P-selectin binding peptide) - to image endothelial activation following cerebral ischemia/reperfusion. MNP-PBP consists of approximately 1000 PBP ligands (primary sequence: GSIQPRPQIHNDGDFEEIPEEYLQ GGSSLVSVLDLEPLDAAWL) conjugated to a 50 nm diameter aminated dextran iron oxide particle. In vitro P- and E-selectin binding was assessed by competition ELISA. Transient focal cerebral ischemia was induced in male C57/BL 6 mice followed by contrast injection (MNP-PBP; MNP-NH2; Feridex; MNP-PBP-FITC) at 24 h after reperfusion and T(2) magnetic resonance imaging at 9.4 T was performed. Infarction and microvasculature accumulation of contrast agent was assessed in coronal brain sections. MNP-PBP attenuated antibody binding to P-selectin by 34.8 +/- 1.7%. P-selectin was preferentially increased in the infarct hemisphere and MNP-PBP-FITC accumulation in the infarct hemisphere microvasculature was observed. Compared with the nontargeted iron oxide agents MNP-NH2 and Feridex, MNP-PBP showed a significantly greater T(2) effect within the infarction. MR imaging of P-selectin expression with a targeted iron oxide nanoparticle contrast agent may reveal early endothelial activation in stroke and other neuroinflammatory states.

Quantified T1 as an adjunct to apparent diffusion coefficient for early infarct detection: a high-field magnetic resonance study in a rat stroke model.

BACKGROUND: Thrombolytic treatment for acute stroke has focused attention on accurate identification of injured vs. salvageable brain tissue, particularly if reperfusion occurs. However, our knowledge of differences in acute magnetic resonance imaging changes between transient and permanent ischemia and how they reflect permanently damaged tissue remain incomplete. AIMS AND/OR HYPOTHESIS: Magnetic resonance imaging characteristics vary widely following ischemia and, at acute times, T1, T2 or apparent diffusion coefficient quantification may differentiate viable tissue from that destined to infarct. METHODS: High-resolution magnetic resonance imaging was performed at 9.4 T following permanent or transient (90 min) middle cerebral artery occlusion in spontaneously hypertensive male rats or Wistar rats. Within 30 min, quantified maps of the apparent diffusion coefficient, T1, and T2 were performed and measures determined for sequences in the infarct and compared with that in the contralateral region. Lesion area for each magnetic resonance imaging sequence (T1, T2, apparent diffusion coefficient, and perfusion maps) was delineated for different time points using quantitative threshold measures and compared with final histological damage. RESULTS: Early extensive changes in T1 following both transient and permanent middle cerebral artery occlusion provided a sensitive early indicator of the final infarct area. Following reperfusion, small but measurable early T2 changes indicative of early development of vasogenic edema occurred in the transient but not permanent groups. In transient middle cerebral artery occlusion, at 70 min apparent diffusion coefficient decreased (P<0.001) and then pseudonormalized at 150 min. In permanent middle cerebral artery occlusion, apparent diffusion coefficient declined over time. Lesion area detected using T1 maps exceeded that with T2 and apparent diffusion coefficient at 70 and 150 min in both groups (P<0.001). CONCLUSIONS: The results indicate that, independent of reperfusion, quantified T1 is superior for detecting early ischemic changes that are not necessarily detected with T2 or apparent diffusion coefficient.

A computational model of the HBK2 potassium channel ion pore.

A computational model of the putative ion pore region of the HBK2 potassium channel was developed. Utilizing experimentally derived constraints, conformations corresponding to both the open and closed states of the ion pore were determined. Also, a conformational basis for the different sensitivites of the internal and external tetraethylammonium binding sites has been proposed. The model presented here suggests a role for other regions of the HBK2 protein in determining the ion pore conformation.