Inhibitory effect of aqueous dandelion extract on HIV-1 replication and reverse transcriptase activity

<p>Abstract</p> <p>Background</p> <p>Acquired immunodeficiency syndrome (AIDS), which is caused by the human immunodeficiency virus (HIV), is an immunosuppressive disease that results in life-threatening opportunistic infections. The general problems in current therapy include the constant emergence of drug-resistant HIV strains, adverse side effects and the unavailability of treatments in developing countries. Natural products from herbs with the abilities to inhibit HIV-1 life cycle at different stages, have served as excellent sources of new anti-HIV-1 drugs. In this study, we aimed to investigate the anti-HIV-1 activity of aqueous dandelion extract.</p> <p>Methods</p> <p>The pseudotyped HIV-1 virus has been utilized to explore the anti-HIV-1 activity of dandelion, the level of HIV-1 replication was assessed by the percentage of GFP-positive cells. The inhibitory effect of the dandelion extract on reverse transcriptase activity was assessed by the reverse transcriptase assay kit.</p> <p>Results</p> <p>Compared to control values obtained from cells infected without treatment, the level of HIV-1 replication and reverse transcriptase activity were decreased in a dose-dependent manner. The data suggest that dandelion extract has a potent inhibitory activity against HIV-1 replication and reverse transcriptase activity. The identification of HIV-1 antiviral compounds from <it>Taraxacum officinale </it>should be pursued.</p> <p>Conclusions</p> <p>The dandelion extract showed strong activity against HIV-1 RT and inhibited both the HIV-1 vector and the hybrid-MoMuLV/MoMuSV retrovirus replication. These findings provide additional support for the potential therapeutic efficacy of <it>Taraxacum officinale</it>. Extracts from this plant may be regarded as another starting point for the development of an antiretroviral therapy with fewer side effects.</p

Anti-influenza virus effect of aqueous extracts from dandelion

<p>Abstract</p> <p>Background</p> <p>Human influenza is a seasonal disease associated with significant morbidity and mortality. Anti-flu Traditional Chinese Medicine (TCM) has played a significant role in fighting the virus pandemic. In TCM, dandelion is a commonly used ingredient in many therapeutic remedies, either alone or in conjunction with other natural substances. Evidence suggests that dandelion is associated with a variety of pharmacological activities. In this study, we evaluated anti-influenza virus activity of an aqueous extract from dandelion, which was tested for in vitro antiviral activity against influenza virus type A, human A/PR/8/34 and WSN (H1N1).</p> <p>Results</p> <p>Results obstained using antiviral assays, minigenome assay and real-time reverse transcription-PCR analysis showed that 0.625-5 mg/ml of dandelion extracts inhibited infections in Madin-Darby canine kidney (MDCK) cells or Human lung adenocarcinoma cell line (A549) of PR8 or WSN viruses, as well as inhibited polymerase activity and reduced virus nucleoprotein (NP) RNA level. The plant extract did not exhibit any apparent negative effects on cell viability, metabolism or proliferation at the effective dose. This result is consistent with the added advantage of lacking any reported complications of the plant's utility in traditional medicine over several centuries.</p> <p>Conclusion</p> <p>The antiviral activity of dandelion extracts indicates that a component or components of these extracts possess anti-influenza virus properties. Mechanisms of reduction of viral growth in MDCK or A549 cells by dandelion involve inhibition on virus replication.</p

Toxic Megacolon and Perforated Fungal Diverticulitis due to Mucor indicus Infection in a Patient with Chronic Myelogenous Leukemia

Introduction: Intestinal zygomycosis is a rare infection by the fungi zygomycetes that have little intrinsic pathogenicity in normal hosts and mainly affects immune compromised patients. Mucor indicus is a rare, emerging cause of intestinal zygomycosis with only 8 reported cases in English literature since 1986.Presentation of Case: We reported an unusual case of toxic megacolon, fungal diverticulitis with perforation and liver abscesses caused by Mucor indicus in a patient with chronic myelogenous leukemia (CML), B-lymphoid blast crisis and pancytopenia. The patient was treated with total colectomy and aggressive systemic anti-fungal regimens consisting of amphotericin, caspofungin and posaconazole. However, his fungal abscess in the liver persisted after colectomy, which was confirmed by liver biopsy at four months after total colectomy. His CML and B-lymphoid blast crisis was successfully treated with hyper-CVAD plus dasatinib and had been in complete remission. The patient was alive and continued to have stable fungal infection in the liver based on CT scan at 32 months after total colectomy, for which he has been on posaconazole monotherapy.Conclusions: Mucor indicus may cause a rare invasive zygomycosis that tends to involve gastrointestinal tract and to disseminate to the liver

Storyfier: Exploring Vocabulary Learning Support with Text Generation Models

Vocabulary learning support tools have widely exploited existing materials, e.g., stories or video clips, as contexts to help users memorize each target word. However, these tools could not provide a coherent context for any target words of learners' interests, and they seldom help practice word usage. In this paper, we work with teachers and students to iteratively develop Storyfier, which leverages text generation models to enable learners to read a generated story that covers any target words, conduct a story cloze test, and use these words to write a new story with adaptive AI assistance. Our within-subjects study (N=28) shows that learners generally favor the generated stories for connecting target words and writing assistance for easing their learning workload. However, in the read-cloze-write learning sessions, participants using Storyfier perform worse in recalling and using target words than learning with a baseline tool without our AI features. We discuss insights into supporting learning tasks with generative models.Comment: To appear at the 2023 ACM Symposium on User Interface Software and Technology (UIST); 16 pages (7 figures, 23 tables

PAF-Mediated MAPK Signaling Hyperactivation via LAMTOR3 Induces Pancreatic Tumorigenesis

SummaryDeregulation of mitogen-activated protein kinase (MAPK) signaling leads to development of pancreatic cancer. Although Ras-mutation-driven pancreatic tumorigenesis is well understood, the underlying mechanism of Ras-independent MAPK hyperactivation remains elusive. Here, we have identified a distinct function of PCNA-associated factor (PAF) in modulating MAPK signaling. PAF is overexpressed in pancreatic cancer and required for pancreatic cancer cell proliferation. In mouse models, PAF expression induced pancreatic intraepithelial neoplasia with expression of pancreatic cancer stem cell markers. PAF-induced ductal epithelial cell hyperproliferation was accompanied by extracellular signal-regulated kinase (ERK) phosphorylation independently of Ras or Raf mutations. Intriguingly, PAF transcriptionally activated the expression of late endosomal/lysosomal adaptor, MAPK and mTOR activator 3 (LAMTOR3), which hyperphosphorylates MEK and ERK and is necessary for pancreatic cancer cell proliferation. Our results reveal an unsuspected mechanism of mitogenic signaling activation via LAMTOR3 and suggest that PAF-induced MAPK hyperactivation contributes to pancreatic tumorigenesis

Frequency and distribution of AP-1 sites in the human genome

The AP-1-binding sequences are promoter/enhancer elements that play an essential role in the induction of many genes in mammalian cells; however, the number of genes containing AP-1 sites remains unknown. In order to better address the overall effect of AP-1 on expression of genes encoded by the entire genome, a genome-wide analysis of the frequency and distribution of AP-1 sites would be useful; yet to date, no such analysis of AP-1 sites or any other promoter/enhancer elements has been performed. We present here our study of the consensus AP-1 site and two single-bp variants showing that the frequency of AP-1 sites in promoter regions is significantly lower than their average rate of occurrence in the whole genomic sequence, as well as the frequency of a random heptanucleotide suggesting that nature has selected for a decrease in the frequency of AP-1 sites in the regulatory regions of genes. In addition, genes containing multiple AP-1 sites are more prevalent than those containing only one copy of an AP-1 site, which again may have evolved to allow for greater signal amplification or integration in the regulation of AP-1 target genes. However, the number of AP-1-regulated genes identified in various studies is far smaller than the number of genes containing potential AP-1 sites, indicating that not all AP-1 sites are activated in a given cell under a given condition, and is consistent with the prediction by others that cellular context determines which AP-1 sites are targeted by AP-1

Ex vivo Dynamics of Human Glioblastoma Cells in a Microvasculature-on-a-Chip System Correlates with Tumor Heterogeneity and Subtypes

The perivascular niche (PVN) plays an essential role in brain tumor stem-like cell (BTSC) fate control, tumor invasion, and therapeutic resistance. Here, a microvasculature-on-a-chip system as a PVN model is used to evaluate the ex vivo dynamics of BTSCs from ten glioblastoma patients. BTSCs are found to preferentially localize in the perivascular zone, where they exhibit either the lowest motility, as in quiescent cells, or the highest motility, as in the invasive phenotype, with migration over long distance. These results indicate that PVN is a niche for BTSCs, while the microvascular tracks may serve as a path for tumor cell migration. The degree of colocalization between tumor cells and microvessels varies significantly across patients. To validate these results, single-cell transcriptome sequencing (10 patients and 21 750 single cells in total) is performed to identify tumor cell subtypes. The colocalization coefficient is found to positively correlate with proneural (stem-like) or mesenchymal (invasive) but not classical (proliferative) tumor cells. Furthermore, a gene signature profile including PDGFRA correlates strongly with the “homing” of tumor cells to the PVN. These findings demonstrate that the model can recapitulate in vivo tumor cell dynamics and heterogeneity, representing a new route to study patient-specific tumor cell functions

Determinants that control the specific interactions between TAB1 and p38α

Previous studies have revealed that transforming growth factor-beta-activated protein kinase 1 (TAB1) interacts with p38 alpha and induces p38 alpha autophosphorylation. Here, we examine the sequence requirements in TAB1 and p38 alpha that drive their interaction. Deletion and point mutations in TAB1 reveal that a proline residue in the C terminus of TAB1 (Pro412) is necessary for its interaction with p38 alpha. Furthermore, a cryptic D-domain-like docking site was identified adjacent to the N terminus of Pro412, putting Pro412 in the (phi(B)+3 position of the docking site. Through mutational analysis, we found that the previously identified hydrophobic docking groove in p38 alpha is involved in this interaction, whereas the CD domain and ED domain are not. Furthermore, chimeric analysis with p38 beta (which does not bind to TAB1) revealed a previously unidentified locus of p38 alpha comprising Thr218 and Ile275 that is essential for specific binding of p38 alpha to TAB1. Converting either of these residues to the corresponding amino acid of p380 abolishes p38 alpha interaction with TAB1. These p38a mutants still can be fully activated by p38 alpha upstream activating kinase mitogen-activated protein kinase kinase 6, but their basal activity and activation in response to some extracellular stimuli are reduced. Adjacent to Thr218 and Ile275 is a site where large conformational changes occur in the presence of docking-site peptides derived from p38 alpha substrates and activators. This suggests that TAB1-induced autophosphorylation of p38 alpha results from conformational changes that are similar but unique to those seen in p38 alpha interactions with its substrates and activating kinases

Strong Neel ordering and luminescence correlation in a two-dimensional antiferromagnet

Magneto-optical effect has been widely used in light modulation, optical sensing and information storage. Recently discovered two-dimensional (2D) van der Waals layered magnets are considered as promising platforms for investigating novel magneto-optical phenomena and devices, due to the long-range magnetic ordering down to atomically-thin thickness, rich species and tunable properties. However, majority 2D antiferromagnets suffer from low luminescence efficiency which hinders their magneto-optical investigations and applications. Here, we uncover strong light-magnetic ordering interactions in 2D antiferromagnetic MnPS3 utilizing a newly-emerged near-infrared photoluminescence (PL) mode far below its intrinsic bandgap. This ingap PL mode shows strong correlation with the Neel ordering and persists down to monolayer thickness. Combining the DFT, STEM and XPS, we illustrate the origin of the PL mode and its correlation with Neel ordering, which can be attributed to the oxygen ion-mediated states. Moreover, the PL strength can be further tuned and enhanced using ultraviolet-ozone treatment. Our studies offer an effective approach to investigate light-magnetic ordering interactions in 2D antiferromagnetic semiconductors

Spatiotemporal distribution and prediction of chlorophyll-a in Ulansuhai lake from an arid area of China

Lake Ulansuhai, a typical shallow lake in an arid area that is economically and ecologically important along the Yellow River, is currently eutrophic. Long-term (2010–2020) data on chlorophyll-a, nutrient, and environmental factors were obtained from three Lake Ulansuhai monitoring stations. The temporal and spatial distribution characteristics of Chl-a were analyzed. Additionally, a hybrid evolutionary algorithm was established to simulate and predict Chl-a, and sensitivity analysis revealed the interaction between environmental factors and eutrophication. The results indicated that (1) the seasonal variation of eutrophication showed an obvious trend of spring &gt; summer &gt; autumn &gt; winter, and the concentration of Chl-a in the inlet was significantly higher than that in the outlet; (2) The inlet, center, and outlet of Ulansuhai Lake are satisfactorily affected by HEA in the best suited method. The fitting coefficients (R2) of the optimal models were 0.58, 0.59, and 0.62 for the three monitoring stations, and the root mean square errors (RMSE) were 3.89, 3.21, and 3.56, respectively; (3) under certain range and threshold conditions, Chl-a increased with the increase of permanganate index, water temperature, dissolved oxygen concentration, and ammonia nitrogen concentration, but decreased with the increase of water depth, Secchi disk depth, pH, and fluoride concentration. The results indicate that the HEA can simulate and predict the dynamics of Chl-a, and identify and quantify the relationships between eutrophication and the threshold data. The research results provide theoretical basis and technical support for the prediction and have great significance for the improvement of water quality and environmental protection in arid and semi-arid inland lakes