Identification, molecular characterization and phylogenetic analysis of a novel nucleorhabdovirus infecting Paris polyphylla var. yunnanensis.

A novel betanucleorhabdovirus infecting Paris polyphylla var. yunnanensis, tentatively named Paris yunnanensis rhabdovirus 1 (PyRV1), was recently identified in Yunnan Province, China. The infected plants showed vein clearing and leaf crinkle at early stage of infection, followed by leaf yellowing and necrosis. Enveloped bacilliform particles were observed using electron microscopy. The virus was mechanically transmissible to Nicotiana bethamiana and N. glutinosa. The complete genome of PyRV1 consists of 13,509 nucleotides, the organization of which was typical of rhabdoviruses, containing six open reading frames encoding proteins N-P-P3-M-G-L on the anti-sense strand, separated by conserved intergenic regions and flanked by complementary 3'-leader and 5'-trailer sequences. The genome of PyRV1 shared highest nucleotide sequence identity (55.1%) with Sonchus yellow net virus (SYNV), and the N, P, P3, M, G, and L proteins showed 56.9%, 37.2%, 38.4%, 41.8%, 56.7%, and 49.4% amino acid sequence identities with respective proteins of SYNV, suggesting RyRV1 belongs to a new species of the genus Betanucleorhabdovirus.

Complete genome sequence analysis of a new potyvirus isolated from Paris polyphylla var. yunnanensis.

The complete genome sequence of a new potyvirus from Paris polyphylla var. yunnanensis was determined. Its genomic RNA consists of 9571 nucleotides (nt), excluding the 3'-terminal poly(A) tail, containing the typical open reading frame (ORF) of potyviruses and encoding a putative large polyprotein of 3061 amino acids. The virus shares 54.20%-59.60% nt sequence identity and 51.80%-57.90% amino acid sequence identity with other potyviruses. Proteolytic cleavage sites and conserved motifs of potyviruses were identified in the polyprotein and within individual proteins. Phylogenetic analysis indicated that the virus was most closely related to lily yellow mosaic virus. The results suggest that the virus should be classified as a member of a novel species within the genus Potyvirus, and we have tentatively named this virus "Paris yunnanensis mosaic chlorotic virus" (PyMCV).

Complete genome sequence of polygonatum mosaic-associated virus 1, a novel member of the genus Potyvirus in China.

The complete genome sequence of a putative novel potyvirus, tentatively named "polygonatum mosaic-associated virus 1" (PMaV1), was sequenced from naturally infected Polygonatum cyrtonema Hua in China. PMaV1 has a typical genome organization of potyviruses with a single large open reading frame (nt 119-9448) that encodes a 3109-aa polyprotein that is predicted to be cleaved into 10 mature proteins by virus-encoded proteases. Pairwise comparisons revealed that PMaV1 shares 71.50% complete genome sequence identity with Polygonatum kingianum virus 4 and 80.00% amino acid sequence identity with Polygonatum kingianum virus 3 of the genus Potyvirus. Phylogenetic analysis indicated that PMaV1 clustered with other potyviruses and that it was most closely related to Polygonatum kingianum virus 3 and Polygonatum kingianum virus 4. These results suggest that PMaV1 is a new member of the genus Potyvirus of the family Potyviridae (Nucleotide sequence data reported are available in the GenBank databases under the accession number OP380926).

High-fidelity carbon dots polarity probes: revealing the heterogeneity of lipids in oncology.

Polarity is an integral microenvironment parameter in biological systems closely associated with a multitude of cellular processes. Abnormal polarity variations accompany the initiation and development of pathophysiological processes. Thus, monitoring the abnormal polarity is of scientific and practical importance. Current state-of-the-art monitoring techniques are primarily based on fluorescence imaging which relies on a single emission intensity and may cause inaccurate detection due to heterogeneous accumulation of the probes. Herein, we report carbon dots (CDs) with ultra-sensitive responses to polarity. The CDs exhibit two linear relationships: one between fluorescence intensity and polarity and the other between polarity and the maximum emission wavelength. The emission spectrum is an intrinsic property of the probes, independent of the excitation intensity or probe concentration. These features enable two-color imaging/quantitation of polarity changes in lipid droplets (LDs) and in the cytoplasm via in situ emission spectroscopy. The probes reveal the polarity heterogeneity in LDs which can be applied to make a distinction between cancer and normal cells, and reveal the polarity homogeneity in cytoplasm.

Quantitative Structure-Activity Relationship Enables the Rational Design of Lipid Droplet-Targeting Carbon Dots for Visualizing Bisphenol A-Induced Nonalcoholic Fatty Liver Disease-like Changes.

Lipid droplets (LDs) play indispensable roles in numerous physiological processes; hence, the visualization of the dynamic behavior of LDs in living cells is of great importance in physiological and pathological research. In this article, the quantitative structure-activity relationship (QSAR) theory was employed as an effective design strategy for the development of organelle-targeting carbon dots (CDs). The lipid-water partition coefficient (Log P) of the QSAR was adopted as a key parameter to predict the cellular uptake and subcellular localization of CDs in live cells. By carefully adjusting the molecular structure and lipophilicity of the precursors, p-phenylenediamine-derivatized nucleolus-targeting hydrophilic CDs were converted to lipophilic CDs [4-piperidinoaniline (PA) CDs] with inherent LD-targeting performance. The PA CDs were able to indicate the dynamic behavior of LDs and visualize the changes of bisphenol A-induced nonalcoholic fatty liver disease-like changes in a cellular model. The QSAR strategy of CDs demonstrated here is expected to be increasingly exploited as a powerful design tool for developing various organelle-targeting CDs.

Systemic Immune-Inflammation Index Predicts 3-Month Functional Outcome in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis.

BACKGROUND AND PURPOSE: Systemic immune-inflammation index (SII), a novel inflammation index derived from counts of circulating platelets, neutrophils and lymphocytes, has been studied in developing incident cancer. However, the clinical value of SII in acute ischemic stroke (AIS) patients had not been further investigated. Therefore, we aimed to explore the association between SII and severity of stroke as well as 3-month outcome of AIS patients. METHODS: A total of 216 AIS patients receiving intravenous thrombolysis (IVT) and 875 healthy controls (HCs) were retrospectively recruited. Blood samples were collected within 24h after admission. Severity of stroke was assessed by the National Institute of Health stroke scale (NIHSS) scores on admission and poor 3-month functional outcome was defined as Modified Rankin Scale (mRS) > 2. RESULTS: SII levels in AIS patients were higher than in HCs. The cut-off value of SII is 545.14×109/L. Patients with SII > 545.14×109/L had higher NIHSS scores (median: 5 vs 9, p < 0.001), a positive correlation between SII and NIHSS was observed (rs = 0.305, p < 0.001). Multivariate logistic regression analyses showed that high SII was one of the independent risk factors for poor prognosis at 3 months of AIS patients (OR = 3.953, 95% CI = 1.702-9.179, p = 0.001). The addition of SII to the conventional prognostic model improved the reclassification (but not discrimination) of the functional outcome (net reclassification index 39.3%, p = 0.007). CONCLUSION: SII is correlated with stroke severity at admission and can be a novel prognostic biomarker for AIS patients treated with IVT.

[Research Progress of Expression and Clinical Significant of EZH2 in Hematological Malignancies--Review].

Enhancer of zeste homolog 2(EZH2) is a histone methyltransferase which regulate gene expression through epigenetic machinery. The abnormal expression of EZH2 has been described in many cancer types. With in-depth study, it was found that EZH2 is involved in the occurrence and development in many kinds of malignant hematologic disease which may play a dual role of oncogenes and tumor suppressor genes. In recent years, the emergence of EZH2 inhibitors provide a new option for the future treatment of hematological malignancies. In this review, the expression and clinical significance of EZH2 in various of hematological tumors were summarized briefly.

Correction: Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial carcinoma of the head and neck region which mainly distributes in southern China and Southeast Asia and has a crucial association with the Epstein-Barr virus. Based on epidemiological data, both incidence and mortality of NPC have significantly declined in recent decades grounded on the improvement of living standard and medical level in an endemic region, in particular, with the clinical use of individualized chemotherapy and intensity-modulated radiotherapy (IMRT) which profoundly contributes to the cure rate of NPC patients. To tackle the challenges including local recurrence and distant metastasis in the current NPC treatment, we discussed the implication of using targeted therapy against critical molecules in various signal pathways, and how they synergize with chemoradiotherapy in the NPC treatment. Combination treatment including targeted therapy and IMRT or concurrent chemoradiotherapy is presumably to be future options, which may reduce radiation or chemotherapy toxicities and open new avenues for the improvement of the expected functional outcome for patients with advanced NPC.

Nanoemulsified adlay bran oil reduces tyrosinase activity and melanin synthesis in B16F10 cells and zebrafish.

The efficacy of oily components is often difficult to evaluate due to their incompatibility with most models. Here, we emulsified adlay bran oil (ABO), processed it to a nanoscale, and investigated its anti-hyperpigmentation efficacy, assessed for its inhibitory effects against tyrosinase activity and melanin production, in an in vitro system (mouse melanoma B16F10 cells) and an in vivo system (zebrafish embryos). ABO induced dose-dependent reductions in tyrosinase activity and melanin production in both the melanoma cells and zebrafish, without affecting viability. The efficacy of ABO was strongly influenced by emulsion particle size in the zebrafish but not in the cells. These results indicate that ABO has potential as a tyrosinase inhibitor and anti-hyperpigmentation agent and that the emulsion system is an effective method for delivering the bioactive components of ABO to living systems that could be utilized for other oily components.

Primary non-Hodgkin lymphoma of the right femur and subsequent metastasis to the left femur: A case report and literature review.

Non-Hodgkin lymphoma of the bone is rare and typically causes an extensive bone lesion. The present study describes a case of diffuse large B-cell primary non-Hodgkin lymphoma of the bone, which occurred in the right femur, and was initially treated with surgery and chemotherapy. Following a 7-year period of complete remission, a new, similar lesion was identified in the left femur. With both lesions, there was no accompanying destruction of any other bones or organ involvement. Metastasis of PLB to the contralateral side is extremely rare and, to the best of our knowledge, this is the first report of this particular presentation in China or worldwide. We hypothesized that the present situation arose due to mechanisms involving the tumor microenvironment, circulating tumor cells, lymphocyte homing and self-seeding. The present report describes the case in detail, and discusses the possible underlying mechanisms and their potential contribution to the treatment of non-Hodgkin lymphoma, as well as the prevention of metastasis and recurrence, which may be of considerable clinical significance.

Deguelin induced differentiation of mutated NPM1 acute myeloid leukemia in vivo and in vitro.

Nucleophosmin (NPM1), a restricted nucleolar localization protein, shuttles between the nucleus and the cytoplasm. Mutated (Mt)-NPM1 protein, which has aberrant cytoplasmic dislocation of nucleophosmin, occurs in approximately one-third of acute myeloid leukemia cases. Deguelin, a rotenoid isolated from several plant species, is a strong antitumor agent. NOD/SCID mice xenografted with human Mt-NPM1 OCI/AML3 cell lines served as in-vivo models. Wright-Giemsa staining and flow cytometry analysis were used for differentiation assays. Associated molecular events were assessed by western blot and histological analyses. Kaplan-Meier estimates were used to calculate survival. Deguelin toxicity in mice was assessed by immunohistochemistry staining and serum markers. Clinical samples were differentiated by flow cytometry analysis. Deguelin induced differentiation by downregulating the Mt-NPM1 protein levels, which was accompanied by a decrease in SIRT1, p21, and HDAC1 and an increase in CEBPß and granulocyte colony-stimulating factor receptor protein expression levels. A low-deguelin dose prolonged survival compared with the control group, and there were no apparent lesions to the brain, liver, heart, and kidney in vivo. In clinical samples, deguelin induced the differentiation of fresh blasts with Mt-NPM1 protein, but not with the wild-type NPM1 protein. Taken together, these findings further provide new evidence that the Mt-NPM1 protein plays an important role in inducing differentiation in vivo and in vitro. Mutated NPM1 protein may be a therapeutic target of deguelin in acute myeloid leukemia with the NPM1 mutation.

Betulinic acid and the pharmacological effects of tumor suppression (Review).

Betulinic acid (BA), a lupane-type pentacyclic triterpenoid saponin from tree bark, has the potential to induce the apoptosis of cancer cells without toxicity towards normal cells in vitro and in vivo. The antitumor pharmacological effects of BA consist of triggering apoptosis via the mitochondrial pathway, regulating the cell cycle and the angiogenic pathway via factors, including specificity protein transcription factors, cyclin D1 and epidermal growth factor receptor, inhibiting the signal transducer and activator of transcription 3 and nuclear factor­κB signaling pathways, preventing the invasion and metastasis of tumor cells, and affecting the expression of topoisomerase I, p53 and lamin B1. In previous years, several studies have shown its antitumor effect, initially applied to malignant melanoma, however, it also has broad efficacies against most solid types of tumor from different regions of the body. There have been few investigations in hematological malignancies, however, this direction may offer potential in such a novel field of research. In this review, the primary pharmacological effects of BA in tumors, particularly in hematological malignancies are discussed.

Steroid receptor coactivator-3 is a pivotal target of gambogic acid in B-cell Non-Hodgkin lymphoma and an inducer of histone H3 deacetylation.

Gambogic acid (GA), the active ingredient from gamboges, has been verified as a potent anti-tumor agent in many cancer cells. Nevertheless, its function in lymphoma, especially in B-cell Non-Hodgkin lymphoma (NHL), remains unclear. Amplification and/or overexpression of steroid receptor coactivator-3 (SRC-3) have been detected in multiple tumors and have confirmed its critical roles in carcinogenesis, progression, metastasis and therapy resistance in these cancers. However, no clinical data have revealed the overexpression of SRC-3 and its role in B-cell NHL. In this study, we demonstrated the anti-tumor effects of GA, which included cell growth inhibition, G1/S phase cell cycle arrest and apoptosis in B-cell NHL. We also verified that SRC-3 was overexpressed in B-cell NHL in both cell lines and lymph node samples from patients. The overexpressed SRC-3 was a central drug target of GA, and its down-regulation subsequently modulated down-stream gene expression, ultimately contributing to apoptosis. Silencing SRC-3 decreased the expression of Bcl-2, Bcl-6 and cyclin D3, but not of NF-κB and IκB-α. GA treatment did not inhibit the activation of AKT signaling pathway, but induced the deacetylation of histone H3 at lysine 9 and lysine 27. Down-regulated SRC-3 was observed to interact with more HDAC1 to mediate the deacetylation of H3. As the component of E3 ligase, Cullin3 was up-regulated and mediated the degradation of SRC-3. Our results demonstrate that GA is a potent anti-tumor agent that can be used for therapy against B-cell NHL, especially against those with an abundance of SRC-3.

miR-137 Suppresses the Phosphorylation of AKT and Improves the Dexamethasone Sensitivity in Multiple Myeloma Cells Via Targeting MITF.

BACKGROUND: Multiple myeloma (MM), a clonal B cell malignancy characterized by the proliferation of plasma cells within the bone marrow, is still an incurable disease, and therefore, finding new therapeutic targets is urgently required. Although microRNA-137 (miR-137), which is involved in a variety of cellular processes, has been reported to be under-expressed in many types of solid tumors, its role in MM is less known. METHODS: In this study, the target gene and the potential effect of miR-137 in MM were investigated. . RESULTS: The results showed significantly down regulated expression of miR-137 in MM cell lines and in the CD138+ bone marrow mononuclear cells of MM patients. A dual luciferase reporter gene analysis revealed that MITF is a direct target of miR-137. The overexpression of miR-137 or transfection of MITF-shRNA had no significant effect on the expression of serine/ threonine protein kinase (AKT), but the expression of MITF, c-MET, p-AKT, and its phosphorylated substrate protein decreased significantly, which was accompanied by an increase in p53 expression. In addition, the overexpression of miR-137 or MITF-shRNA significantly improved the 36-hour inhibition rate and apoptosis rate in multiple myeloma cells treated with dexamethasone. The overexpression of MITF could counteract the biological effect of miR-137 in multiple myeloma cells. CONCLUSION: We conclude that MITF is a direct target of miR-137. The miR-137 can improve the dexamethasone sensitivity in multiple myeloma cells by reducing the c-MET expression and further decreasing the AKT phosphorylation via targeting MITF.