Research progress in the pathogenesis and prognosis of ZNF384 fusion subtype acute leukemia

Gene fusions caused by chromosomal translocations have become the main pathogenic factors that initiate leukemogenesis. Zinc finger protein 384 (ZNF384) fusion, as an atypical fusion gene in acute leukemia (AL), has widely been identified in different age groups. ZNF384 rearranged 18 genes, with E1A binding protein p300 (EP300), transcription factor 3, (TCF3), and TATA-box binding protein-associated factor 15 (TAF15) being the most common fusion partners. These fusion proteins maintain the complete structure of ZNF384, but the fusion partners are missing in varying degrees, indicating that the mechanisms behind different subtypes of carcinogenesis have similarities. The mechanism of ZNF384-rearranged AL is also being actively investigated. It is mainly believed that the fusion protein regulates the transcription and expression of downstream proteins through chromatin remodeling, and plays a potential role in the differentiation of hematopoietic stem cells, the proliferation and apoptosis of cancer cells and genome repair. Patients with ZNF384 fusions express both lymphoid and myeloid-specific antigens, which have lineage-transforming properties during disease progression. The diversity of immunophenotypes leads to ambiguity in treatment options and diverse outcomes in prognosis studies, and affects the clinical outcome of patients together with fusion subtype and age of onset. Through the statistical analysis of published cases and large-scale cohort studies in the past 10 years, the incidence of ZNF384 fusion in AL and the frequency of each fusion subtype in the context of existing research were further confirmed. The impact of different treatment methods on the prognosis of patients was analyzed, and the identified mechanisms were summarized in order to provide reference for subsequent diagnosis, treatment and research of this unique AL subtype

Interleukin-35 Expression in Non-Small Cell Lung Cancer is Associated with Tumor Progression

Background/Aims: Lung cancer continues to be the leading cause of cancer related deaths worldwide due to its high incidence, malignant behavior and lack of major advancements in treatment strategy. The occurrence and development of lung cancer is closely related to inflammation. Thus, we conducted the present study to investigate the effects of IL-35 (Interleukin 35), a newly identified anti-inflammatory factor, on non-small cell lung cancer (NSCLC), which accounts for about 85% of all lung cancers. Methods: We first evaluated the IL-35 expression in 384 pairs of NSCLC samples and their adjacent normal mucosa by realtime PCR, ELISA (Enzyme-linked immunoassay) and tissue microarrays. Then the role of IL-35 on patient survival rates, cancer progression and their sensitivity to chemotherapy drugs were assessed. Results: IL-35 was barely expressed in the NSCLC tissues but highly expressed in the adjacent normal tissues. The down-regulation of IL-35 was significantly correlated with the results of American Joint Committee on Cancer stage, differentiation and it was also shown to be an independent prognostic indicator of disease-free survival and overall survival for patients with NSCLC. Overexpression of IL-35 in NSCLC cells suppressed cell migration, invasion, proliferation, colony formation through suppressing β-catenin. IL-35 inhibited NSCLC formation in the mice model and sensitize the cancer cells to chemotherapy drugs. Conclusion: Our results showed that IL-35 plays an inhibitory role in NSCLC development and function as a novel prognostic indicator and a potential therapeutic target

Structural and functional characterization of Pseudomonas aeruginosa CupB chaperones

Pseudomonas aeruginosa, an important human pathogen, is estimated to be responsible for,10% of nosocomial infections worldwide. The pathogenesis of P. aeruginosa starts from its colonization in the damaged tissue or medical devices (e. g. catheters, prothesis and implanted heart valve etc.) facilitated by several extracellular adhesive factors including fimbrial pili. Several clusters containing fimbrial genes have been previously identified on the P. aeruginosa chromosome and named cup [1]. The assembly of the CupB pili is thought to be coordinated by two chaperones, CupB2 and CupB4. However, due to the lack of structural and biochemical data, their chaperone activities remain speculative. In this study, we report the 2.5 A crystal structure of P. aeruginosa CupB2. Based on the structure, we further tested the binding specificity of CupB2 and CupB4 towards CupB1 (the presumed major pilus subunit) and CupB6 (the putative adhesin) using limited trypsin digestion and strep-tactin pull-down assay. The structural and biochemical data suggest that CupB2 and CupB4 might play different, but not redundant, roles in CupB secretion. CupB2 is likely to be the chaperone of CupB1, and CupB4 could be the chaperone of CupB4:CupB5:CupB6, in which the interaction of CupB4 and CupB6 might be mediated via CupB5

Amyloid and SCD jointly predict cognitive decline across Chinese and German cohorts.

INTRODUCTION Subjective cognitive decline (SCD) in amyloid-positive (Aβ+) individuals was proposed as a clinical indicator of Stage 2 in the Alzheimer's disease (AD) continuum, but this requires further validation across cultures, measures, and recruitment strategies. METHODS Eight hundred twenty-one participants from SILCODE and DELCODE cohorts, including normal controls (NC) and individuals with SCD recruited from the community or from memory clinics, underwent neuropsychological assessments over up to 6 years. Amyloid positivity was derived from positron emission tomography or plasma biomarkers. Global cognitive change was analyzed using linear mixed-effects models. RESULTS In the combined and stratified cohorts, Aβ+ participants with SCD showed steeper cognitive decline or diminished practice effects compared with NC or Aβ- participants with SCD. These findings were confirmed using different operationalizations of SCD and amyloid positivity, and across different SCD recruitment settings. DISCUSSION Aβ+ individuals with SCD in German and Chinese populations showed greater global cognitive decline and could be targeted for interventional trials. HIGHLIGHTS SCD in amyloid-positive (Aβ+) participants predicts a steeper cognitive decline. This finding does not rely on specific SCD or amyloid operationalization. This finding is not specific to SCD patients recruited from memory clinics. This finding is valid in both German and Chinese populations. Aβ+ older adults with SCD could be a target population for interventional trials

Structural study of levansucrase by x-ray crystallography

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

A typical bedside-to-bench investigation of leukemogenic driver MEF2D fusion reveals new targeted therapy in B-cell acute lymphoblastic leukemia

B-cell acute lymphoblastic leukemia (B-ALL) is a malignant tumor originating from B-lineage lymphoid precursor cells. The incidence of B-ALL is about 80% in childhood acute leukemia and 20% in adults. In recent years, with standardized treatment guided by risk stratification, the long-term disease-free survival rate of children is about 80%, while that of adults is less than 40%. However, the specific pathogenesis of the newly identified B-ALL and the targeted therapy strategies have not been vigorously investigated. In this review, we highlight the recent breakthroughs in mechanistic studies and novel therapeutic options in DUX4- and MEF2D-subtype B-ALLs

Donor substrate recognition in the raffinose-bound E342A mutant of fructosyltransferase levansucrase-2

indicated by dashed green lines. Residues making van der Waals or hydrophobic contacts are indicated by the 'bent comb' symbol. Water molecules appear as spheres in light blue, carbon, oxygen and nitrogen are in black, red and dark blue, respectively.<p><b>Copyright information:</b></p><p>Taken from "Donor substrate recognition in the raffinose-bound E342A mutant of fructosyltransferase levansucrase"</p><p>http://www.biomedcentral.com/1472-6807/8/16</p><p>BMC Structural Biology 2008;8():16-16.</p><p>Published online 17 Mar 2008</p><p>PMCID:PMC2277421.</p><p></p