THE USE OF MANDAMUS TO COMPEL EDUCATIONAL INSTITUTIONS TO CONFER DEGREES

Hispolon is an active phenolic compound of <i>Phellinus igniarius</i>, a mushroom that was recently shown to have antioxidant and anticancer activities in various solid tumors. Here, the molecular mechanisms by which hispolon exerts anticancer effects in acute myeloid leukemia (AML) cells was investigated. The results showed that hispolon suppressed cell proliferation in the various AML cell lines. Furthermore, hispolon effectively induced apoptosis of HL-60 AML cells through caspases-8, -9, and -3 activations and PARP cleavage. Moreover, treatment of HL-60 cells with hispolon induced sustained activation of JNK1/2, and inhibition of JNK by JNK1/2 inhibitor or JNK1/2-specific siRNA significantly abolished the hispolon-induced activation of the caspase-8/-9/-3. In vivo, hispolon significantly reduced tumor growth in mice with HL-60 tumor xenografts. In hispolon-treated tumors, activation of caspase-3 and a decrease in Ki67-positive cells were observed. Our results indicated that hispolon may have the potential to serve as a therapeutic tool to treat AML

Plasmon-Enhanced Photodynamic Cancer Therapy by Upconversion Nanoparticles Conjugated with Au Nanorods

Photodynamic therapy (PDT) based on photosensitizers (PSs) constructed with nanomaterials has been widely applied to treat cancer. This therapy is characterized by an improved PS accumulation in tumor regions. However, challenges, such as short penetration depth of light and low extinction coefficient of PSs, limit PDT applications. In this study, a nanocomposite consisting of NaYF₄:Yb/Er upconversion nanoparticles (UCPs) conjugated with gold nanorods (Au NRs) was developed to improve the therapeutic efficiency of PDT. Methylene blue (MB) was embedded in a silica shell for plasmon-enhanced PDT. UCPs served as a light converter from near-infrared (NIR) to visible light to excite MB to generate reactive oxygen species (ROS). Au NRs could effectively enhance upconversion efficiency and ROS content through a localized surface plasmon resonance (SPR) effect. Silica shell thickness was adjusted to investigate the optimized MB loading amount, ROS production capability, and efficient distance for plasmon-enhanced ROS production. The mechanism of plasmon-enhanced PDT was verified by enhancing UC luminescence intensity through the plasmonic field and by increasing the light-harvesting capability and absorption cross section of the system. This process improved the ROS generation by comparing the exchange of Au NRs to Au nanoparticles with different SPR bands. NIR-triggered nanocomposites of UCP@SiO₂:MB-NRs were significantly confirmed by improving ROS generation and further modifying folic acid (FA) to develop an active component targeting OECM-1 oral cancer cells. Consequently, UCP@SiO₂:MB-NRs-FA could highly produce ROS and undergo efficient PDT in vitro and in vivo. The mechanism of PDT treatment by UCP@SiO₂:MB-NRs-FA was evaluated via the cell apoptosis pathway. The proposed process is a promising strategy to enhance ROS production through plasmonic field enhancement and thus achieve high PDT therapeutic efficacy

Additional file 3: of AKR1C1 controls cisplatin-resistance in head and neck squamous cell carcinoma through cross-talk with the STAT1/3 signaling pathway

Figure S1. In vivo tumor growth abilities in HNSCC cells. Figure S2. Full length Western blot images. (DOCX 2354 kb

Additional file 2: of AKR1C1 controls cisplatin-resistance in head and neck squamous cell carcinoma through cross-talk with the STAT1/3 signaling pathway

Table S2. Clinical Characteristics of AKR1C1 in TCGA HNSCC cohorts (DOCX 24 kb

Additional file 1: of Adenylate kinase 4 modulates oxidative stress and stabilizes HIF-1α to drive lung adenocarcinoma metastasis

Table S1. Correlation of clinicopathological features of NSCLC patients with AK4 and HIF-1α expression. Figure S1. (related to Fig. 1) Ingenuity upstream analysis of consensus AK4 metabolic gene signature between GSE31210 and TCGA LUAD. A, Venn diagram analysis of AK4 metabolic gene signature in GSE31210 and TCGA LUAD datasets. Activation z score more than 2 or less than − 2 is predicted to be significant activation or inhibition respectively. B, Left panel, Ingenuity upstream analysis of consensus AK4 metabolic signature. Right panel, heatmap illustrates HIF-1 α -regulated genes that are positively or negatively correlated with AK4 expression in consensus AK4 metabolic signature. Figure S2. (related to Fig. 3) AK4-induced EMT is HIF-1α-dependent. A, WB analysis of AK4, HIF-1α, GnT-V, E-cadherin, Vimentin, Snail from CL1-0 vector- or AK4-expressing cells transduced with shNS or shHIF-1α in Hx.B, Invasion assay of CL1-0 vector- or AK4-expressing cell transduced with shNS or shHIF-1α in Hx. The results are presented as the mean ± SD of at least three separate experiments. Two-tailed, unpaired Student’s t tests were used for all pairwise comparisons. *P ≤ 0.05; **P ≤ 0.01. Figure S3. (related to Fig. 4) Differentially expressed genes in glycolysis/gluconeogenesis and glutathione metabolism in CL1-0 upon AK4 overexpression. A, Relative expression level of genes in KEGG glycolysis and gluconeogenesis pathway from CL1-0 AK4 versus CL1-0 Vec microarray data. B, Relative expression level of genes in KEGG glutathione metabolism pathway from CL1-0 AK4 versus CL1-0 Vec microarray data. Figure S4. (related to Fig. 6) MTT assay cell viability assay of digitoxigenin, lanatoside C, digoxin, proscillaridin, and withaferin-A in CL1-0, CL1-5, CL1-0 Vec, and CL1-0 AK4. Figure S5. (related to Fig. 6) Withaferin-A treatment suppresses metastasis in A549 orthotopic lung cancer mouse model. A, 5 A549-GL cells were orthotopically injected into the left lung of NSG mice that were treated over an interval of one day with DMSO vehicle control or withaferin-A: 1.0 mg/kg; 4.0 mg/kg. Luminescence was measured using a noninvasive, bioluminescence imaging system (IVIS spectrum) at days 1 (top) and 28 (bottom). B, Luminescence, fluorescence, gross view (formalin-fixed) and H&E staining images in the lungs of mice treated with DMSO vehicle control or withaferin-A (1.0 mg/kg or 4.0 mg/kg) at day 28 after orthotopic injection of A549-GL cells (top). Quantification of tumor weight in the lung of mice treated with DMSO vehicle control or withaferin-A (1.0 mg/kg or 4.0 mg/kg) at day 28 after orthotopic injection of A549-GL cells (bottom). C, Luminescence, fluorescence, gross view (formalin-fixed) and H&E staining images in the livers of mice treated with DMSO vehicle control or withaferin-A (1.0 mg/kg or 4.0 mg/kg) at day 28 after orthotopic injection of A549-GL cells (top). Quantification of liver nodule number in the mice treated with DMSO vehicle control or withaferin-A (1.0 mg/kg or 4.0 mg/kg) at day 28 after orthotopic injection of A549-GL cells (bottom). The results are presented as the mean ± SD of at least three separate experiments. Two-tailed, unpaired Student’s t tests were used for all pairwise comparisons. *P ≤ 0.05; **P ≤ 0.01. (PDF 3400 kb

Dengue virus infection is through a cooperative interaction between a mannose receptor and CLEC5A on macrophage as a multivalent hetero-complex.

<p><b>(a)</b> Binding model of dengue virus with MR/DC-SIGN and CLEC5A on GM-MDM cell membrane. <b>(b)</b> The strong avidity receptor captures dengue virus to facilitate the interaction with a weak-binding signal receptor in proximity to induce innate immune response.</p

Additional file 1: of AKR1C1 controls cisplatin-resistance in head and neck squamous cell carcinoma through cross-talk with the STAT1/3 signaling pathway

Table S1. Reagents and primer information in this manuscript (DOCX 23 kb

Additional file 5 of AKR1C1 controls cisplatin-resistance in head and neck squamous cell carcinoma through cross-talk with the STAT1/3 signaling pathway

Table S4. AKR1C1 regulates Up-stream Regulators from Ingenuity Pathway Analysis (DOCX 16 kb

Additional file 4 of AKR1C1 controls cisplatin-resistance in head and neck squamous cell carcinoma through cross-talk with the STAT1/3 signaling pathway

Table S3. AKR1C1 controls cellular functions from Ingenuity Pathway Analysis (DOCX 17 kb