13 research outputs found

    Data_Sheet_1_Dietary Phosphorus Reduced Hepatic Lipid Deposition by Activating Ampk Pathway and Beclin1 Phosphorylation Levels to Activate Lipophagy in Tilapia Oreochromis niloticus.docx

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    High-phosphorus diet (HPD) reduces lipid deposition and significantly influences lipid metabolism. However, the relevant mechanism is unknown. Herein, using widely-cultured teleost tilapia Oreochromis niloticus as the experimental animals, we found that HPD and Pi incubation reduced triglyceride (TG) content (P ≤ 0.05), suppressed lipogenesis, activated AMP-activated protein kinase (AMPK) pathway and autophagy (P ≤ 0.05), and increased fatty acid β-oxidation and lipolysis in tilapia liver and hepatocytes (P ≤ 0.05). Our further investigation indicated that Pi treatments activated the lipophagy and facilitated mitochondrial fatty acid β-oxidation, and according reduced TG deposition (P ≤ 0.05). Mechanistically, phosphorus increased the AMPKα1 phosphorylation level at S496 and Beclin1 phosphorylation at S90, and Beclin1 phosphorylation by AMPKα1 was required for phosphorus-induced lipophagy and lipolysis. Our study revealed a mechanism for Beclin1 regulation and autophagy induction in response to high-phosphorus diet, and provided novel evidences for the link between dietary phosphorus addition and lipolytic metabolism via the AMPK/Beclin1 pathway. Our results also suggested that AMPK should be the potential target for the prevention and control of lipid metabolic disorders. Overall, these results suggested that HPD reduced hepatic lipid deposition by activating AMPK pathway and Beclin1 phosphorylation levels to activate lipophagy, which provided potential targets for the prevention and control of fatty liver in fish.</p

    The Expression of CD30 Based on Immunohistochemistry Predicts Inferior Outcome in Patients with Diffuse Large B-Cell Lymphoma

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    <div><p>The prognostic value of CD30 expression indiffuse large B-cell lymphoma (DLBCL)remains controversial. Herein, we performed this retrospective study to investigate the clinical and prognostic significance of CD30 expression in patients with DLBCL.Among all the 146 patients, the expression of CD30 was observed in 23 cases (15.7%).The DLBCL patients with CD30 expression showed more likely to present B symptoms, bone marrow involvement, non-germinal centre B-cell-like (Non-GCB) DLBCL, BCL-2 and Ki-67overexpression(p<0.05). Patients with CD30 expression showed significantly poor overall and event-free survivalcompared with CD30 negative patients(p = 0.031 and 0.041, respectively), especially those with the high intermediate/high-risk international prognostic index (IPI)(p = 0.001 and 0.007, respectively). The prognostic value of CD30expression retained in DLBCL patients treated with eitherCHOP (cyclophosphamide, doxorubicin, vincristine,prednisone) or R-CHOP(rituximab+CHOP). The multivariate analysisrevealed that the expression of CD30 remained an unfavorable factor for both overall and event-free survival (p = 0.001 and 0.002, respectively).In conclusion, these data suggest that CD30 is expressed predominantly in Non-GCBDLBCL. The expression of CD30 implied poor outcomein DLBCL patientstreated with either CHOP or R-CHOP, especially those with the high intermediate/high-risk IPI, possibly indicating that anti-CD30 monoclonal antibody could be of clinical interest.</p></div

    Multivariate Cox regression analysis for survival.

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    <p>LDH, Lactate dehydrogenase; IPI,internationalprognosticindex; HR, hazard ratio</p><p>95%CI, 95confidence interval</p><p>Multivariate Cox regression analysis for survival.</p

    Clinical characteristics of patients according to CD30 expression.

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    <p>LDH, Lactate dehydrogenase; BM, bone marrow;IPI,internationalprognosticindex</p><p>COO, cell of origin;GCB,germinal center B-cell like.</p><p>Clinical characteristics of patients according to CD30 expression.</p

    Kaplan-Meier curve for overall survival (OS) and event-free survival (EFS) according to the expression of CD30 and IPI.

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    <p>OS (A) and EFS (B) for high intermediate/high IPI risk patients (IPI = 3–5) with and without CD30 expression; OS (C) and EFS (D) for low/ low intermediate risk IPIpatients (IPI = 0–2)with and without CD30 expression.</p

    Kaplan-Meier curve for overall survival (OS) and event-free survival (EFS) according to the expression of CD30 and treatment.

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    <p>OS (<b>A</b>) and EFS (<b>B</b>) according to CD30 expression in DLBCL patients treated with CHOP. OS (<b>C</b>) and EFS (<b>D</b>) according to CD30 expression in DLBCL patients treated with R-CHOP.</p

    Additional file 2 of Klf4-Sirt3/Pparα-Lcad pathway contributes to high phosphate-induced lipid degradation

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    Additional file 1: Supplemental Text S1. Yellow catfish primary intestinal epithelial cells (IECs) isolation and culture. Supplemental Table S1. Feed formulation and proximate analysis of experimental diets. Supplemental Table S2. Primers used for quantitative real-time PCR analysis. Supplemental Table S3. Primers used for plasmid construction of expression vector. Supplemental Table S4. Primers used for plasmid construction of si-klf4. Supplemental Table S5. Primers used for plasmid construction of promoters. Supplemental Table S6. Primers used for site-mutation analysis. Supplemental Table S7. Primers used for electrophoretic mobility-shift assay. Supplemental Table S8. Effects of dietary phosphorus supplementation on growth performance and feed utilization of yellow catfish. Supplemental Figure S1. MTT assay of primary IECs under Pi incubation. Supplemental Figure S2. Immunofluorescent staining of KLF4 protein under Pi incubation. Supplemental Figure S3. Nucleotide sequence of yellow catfish sirt3 promoter. Numbers are relative to the transcription start site (+1). Supplemental Figure S4. ERRα response elements (ERE) located at −1443 bp to −1457 bp and KLF4 response elements (KRE) located at −406 bp to −419 bp of pparα promoter. Supplemental Figure S5. Relative luciferase activity of sirt3 promoter after the incubation with different overexpression vectors. Supplemental Figure S6. The immunoprecipitation experiment for the analysis of KLF4 and ERRα binding with SIRT3. Supplemental Figure S7. Nucleotide sequence of yellow catfish pparα promoter. Numbers are relative to the transcription start site (+1). Supplemental Figure S8. KLF4 response elements (ERE) located at −1443 bp to −1457 bp (KRE1) and −406 bp to −419 bp (KRE2) of pparα promoter. Supplemental Figure S9. Nucleotide sequence of yellow catfish lcad promoter. Numbers are relative to the transcription start site (+1)

    Cancer-Cell-Biomimetic Carbazole-Based AIE Nanoplatform for Targeted Phototheranostics of Lung Cancer

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    Lung cancer is one of the most diagnosed cancers and is the leading cause of cancer death. Photodynamic therapy (PDT) has been considered as a promising strategy due to its strong efficacy and negligible side effects. The development of potent PDT agents with an excellent tumor targeting capability is highly desirable but still not satisfied. In this work, we report a highly efficacious organic nanoplatform based on an aggregation-induced emission luminogen (AIEgen) and biomimetic modification for precise phototheranostics of lung cancer. An AIEgen with strong light absorption ability and bright deep red/near-infrared emission is designed and synthesized that possesses both type I and type II PDT processes. The AIEgen is encapsulated into nanoparticles (NPs) and further camouflaged with a Lewis lung carcinoma cell membrane to build a biomimetic nanoplatform. Both in vitro and in vivo experiments indicate that the cancer-cell-biomimetic NPs could significantly increase the tumor cell targeting ability and sensitively delineate the tumor site. Moreover, the cell-membrane-camouflaged NPs also show excellent antitumor efficacy in lung-cancer-bearing mice. This work demonstrates that the integration of highly efficient AIEgen and biomimetic cell membranes is able to boost the phototheranostic efficacy, representing a promising strategy for precise cancer diagnosis and treatment
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