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| 2. |
- Hua, Dong, et al.
(författare)
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Small interfering RNA-directed targeting of toll-like receptor 4 inhibits human prostate cancer cell invasion, survival, and tumorigenicity
- 2009
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Ingår i: Molecular Immunology. - : Elsevier BV. - 0161-5890 .- 1872-9142. ; 46:15, s. 2876-2884
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Tidskriftsartikel (refereegranskat)abstract
- A major cause of tumor treatment failure is cancer cell metastasis. Toll-like receptor 4 (TLR4)-mediated signaling has been implicated in tumor cell invasion, survival, and metastasis in a variety of cancers. In this study, we investigated the biological roles of TLR4 in prostate metastatic cell invasion and survival, and the potential of gene silencing of TLR4 using small interfering RNA (siRNA) for treatment of cancer. In cultured human prostate cancer cell lines, TLR4 were higher PC3 and DU145 as compared with the poorly metastatic LNCaP indicating that up-regulation of TLR4 was positively correlated with metastasis of tumor cell. In the highly metastatic cancer cell PC3, gene silencing of TLR4 using siRNA significantly inhibited TLR4 mRNA expression and protein level. Knockdown of TLR4 in PC3 cells resulted in a dramatic reduction of tumor cell migration and invasion as indicated by a Matrigel invasion assay. Furthermore, TLR4 siRNA suppressed cell viability and ultimately caused the induction of apoptotic cell death. The effects were associated with abrogating TLR4-mediated signaling to downstream target molecules such as myeloid differentiation factor 88 (MyD88), adaptor-inducing IFN-beta (TRIF), and interferon regulatory factor-1 (IRF-1). In a mouse prostate cancer model, administration with the plasmid construct expressing siRNA for TLR4 obviously inhibited established tumor growth and survival. These studies revealed evidence of a multifaceted signaling network operating downstream of TLR4-mediated tumor cell invasion, proliferation, and survival. Thus, RNA interference-directed targeting of TLR4 may raise the potential of its application for cancer therapy.
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| 3. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 5. |
- Hu, Li-Peng, et al.
(författare)
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Terbinafine prevents colorectal cancer growth by inducing dNTP starvation and reducing immune suppression
- 2022
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Ingår i: Molecular Therapy. - : Elsevier BV. - 1525-0024 .- 1525-0016. ; 30:10, s. 3284-3299
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Tidskriftsartikel (refereegranskat)abstract
- Existing evidence indicates that gut fungal dysbiosis might play a key role in the pathogenesis of colorectal cancer (CRC). We sought to explore whether reversing the fungal dysbiosis by terbinafine, an approved antifungal drug, might inhibit the development of CRC. A population-based study from Sweden identified a total of 185 patients who received terbinafine after their CRC diagnosis and found that they had a decreased risk of death (hazard ratio=0.50) and metastasis (hazard ratio=0.44) compared with patients without terbinafine administration. In multiple mouse models of CRC, administration of terbinafine decreased the fungal load, the fungus-induced myeloid-derived suppressor cell (MDSC) expansion, and the tumor burden. Fecal microbiota transplantation from mice without terbinafine treatment reversed MDSC infiltration and partially restored tumor proliferation. Mechanistically, terbinafine directly impaired tumor cell proliferation by reducing the ratio of nicotinamide adenine dinucleotide phosphate (NADP+) to reduced form of nicotinamide adenine dinucleotide phosphate (NADPH), suppressing the activity of glucose-6-phosphate dehydrogenase (G6PD), resulting in nucleotide synthesis disruption, deoxyribonucleotide (dNTP) starvation and cell cycle arrest. Collectively, terbinafine can inhibit CRC by reversing fungal dysbiosis, suppressing tumor cell proliferation, inhibiting fungus-induced MDSC infiltration, and restoring antitumor immune response.
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| 6. |
- Li, Wenting, et al.
(författare)
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Recent progress in silver nanowire networks for flexible organic electronics
- 2020
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Ingår i: Journal of Materials Chemistry C. - : ROYAL SOC CHEMISTRY. - 2050-7526 .- 2050-7534. ; 8:14, s. 4636-4674
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Forskningsöversikt (refereegranskat)abstract
- Recently, flexible transparent electrodes (FTEs) have attracted extensive attention as an essential element for future organic electronics (OEs), i.e. solution-processable, scalable and flexible organic electronics (FOEs). Although the traditional transparent electrode indium tin oxide (ITO) has been widely used in OEs, its brittleness and high cost significantly limit its application in the next generation of devices, typically flexible electronics. Thus, many alternatives, such as graphene, carbon nanotubes, conductive polymers, metal nanowires, metal grids and electrospun metallic nanofibers, have arisen at the forefront of FTEs. Among them, silver nanowire (AgNW) networks have attracted particular attention due to their excellent electrical conductivity and high transmittance, as well as facile availability and low cost. Since many studies on AgNWs have been published, a comprehensive review highlighting the advantages of AgNWs in FOEs is highly required. In this review, the synthesis and film fabrication of AgNWs have been firstly summarized, focusing especially on the properties of conductivity and light transmittance. Next, post treatments with different approaches to improve the conductivity of AgNWs have been included. And then, characterization of FTEs has been introduced with details on key parameters for FOEs. Furthermore, AgNW-based FOEs have been summarized to demonstrate the recent progress, such as organic light-emitting diodes (OLEDs), organic solar cells (OSCs), light-emitting electrochemical cells (LECs), organic field effect transistors (OFETs), organic memory devices (OMDs), etc. Finally, perspectives for AgNWs in FOEs have been discussed and concluded as well. It is expected that AgNWs could be the focus of future FOEs compared with other alternatives in terms of their advantages of optoelectronic properties, film-formation, solution-processability and flexibility.
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| 7. |
- Lin, Danyang, et al.
(författare)
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A Si-containing FeCoCrNi high-entropy alloy with high strength and ductility synthesized in situ via selective laser melting
- 2020
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Ingår i: Additive Manufacturing. - : Elsevier. - 2214-8604 .- 2214-7810. ; 35
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Tidskriftsartikel (refereegranskat)abstract
- To widen the applications of new materials in additive manufacturing (AM), the traditional method of printing using pre-alloyed powders should be improved because the pre-alloying process is expensive and makes it difficult to adjust the composition of new materials. This study investigates the synthesis of a FeCoCrNi high-entropy alloy (HEA) containing 1.5 at.% Si in situ using selective laser melting (SLM). A remelting strategy and process optimization based on polynomial regression modeling allowed for the printing of almost fully dense (99.78 %) samples. The samples comprised columnar grains, each containing numerous subgrains of a single-phase face-centered cubic solid solution. No precipitation or segregation were observed. The room temperature tensile properties of the samples were excellent, with yields and tensile strengths reaching 701 +/- 14 and 907 +/- 25 MPa, respectively, and an elongation at fracture of 30.8 +/- 2%. These properties were attributed to solid solution strengthening and novel dislocation loop strengthening mechanism. These findings demonstrate that HEAs with a high relative density and good mechanical properties can be directly synthesized by SLM using inexpensive pure metal powders, thereby extending the application potential of AM to manufacture new materials.
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| 8. |
- Nie, Huizhen, et al.
(författare)
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The short isoform of PRLR suppresses the pentose phosphate pathway and nucleotide synthesis through the NEK9-Hippo axis in pancreatic cancer
- 2021
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Ingår i: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 11:8, s. 3898-3915
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Tidskriftsartikel (refereegranskat)abstract
- Prolactin binding to the prolactin receptor exerts pleiotropic biological effects in vertebrates. The prolactin receptor (PRLR) has multiple isoforms due to alternative splicing. The biological roles and related signaling of the long isoform (PRLR-LF) have been fully elucidated. However, little is known about the short isoform (PRLR-SF), particularly in cancer development and metabolic reprogramming, a core hallmark of cancer. Here, we reveal the role and underlying mechanism of PRLR-SF in pancreatic ductal adenocarcinoma (PDAC). Methods: A human PDAC tissue array was used to investigate the clinical relevance of PRLR in PDAC. The in vivo implications of PRLR-SF in PDAC were examined in a subcutaneous xenograft model and an orthotopic xenograft model. Immunohistochemistry was performed on tumor tissue obtained from genetically engineered KPC (KrasG12D/+; Trp53R172H/+; Pdx1-Cre) mice with spontaneous tumors. 13C-labeled metabolite measures, LC-MS, EdU incorporation assays and seahorse analyses were used to identify the effects of PRLR-SF on the pentose phosphate pathway and glycolysis. We identified the molecular mechanisms by immunofluorescence, coimmunoprecipitation, proximity ligation assays, chromatin immunoprecipitation and promoter luciferase activity. Public databases (TCGA, GEO and GTEx) were used to analyze the expression and survival correlations of the related genes. Results: We demonstrated that PRLR-SF is predominantly expressed in spontaneously forming pancreatic tumors of genetically engineered KPC mice and human PDAC cell lines. PRLR-SF inhibits the proliferation of PDAC cells (AsPC-1 and BxPC-3) in vitro and tumor growth in vivo. We showed that PRLR-SF reduces the expression of genes in the pentose phosphate pathway (PPP) and nucleotide biosynthesis by activating Hippo signaling. TEAD1, a downstream transcription factor of Hippo signaling, directly regulates the expression of G6PD and TKT, which are PPP rate-limiting enzymes. Moreover, NEK9 directly interacts with PRLR-SF and is the intermediator between PRLR and the Hippo pathway. The PRLR expression level is negatively correlated with overall survival and TNM stage in PDAC patients. Additionally, pregnancy and lactation increase the ratio of PRLR-SF:PRLR-LF in the pancreas of wild-type mice and subcutaneous PDAC xenograft tumors. Conclusion: Our characterization of the relationship between PRLR-SF signaling, the NEK9-Hippo pathway, PPP and nucleotide synthesis explains a mechanism for the correlation between PRLR-SF and metabolic reprogramming in PDAC progression. Strategies to alter this pathway might be developed for the treatment or prevention of pancreatic cancer.
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| 9. |
- Qin, Gang, et al.
(författare)
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A novel face-centered-cubic high-entropy alloy strengthened by nanoscale precipitates
- 2019
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Ingår i: Scripta Materialia. - : PERGAMON-ELSEVIER SCIENCE LTD. - 1359-6462 .- 1872-8456. ; 172, s. 51-55
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Tidskriftsartikel (refereegranskat)abstract
- A new single-phase face-centered-cubic (FCC) Co9Cr7Cu36Mn25Ni23 [atomic percent, similar hereinafter] high-entropy alloy (HEA) was prepared by arc melting. A uniform distribution of nanometer-sized precipitates was achieved. The tensile yield strength, ultimate tensile strength, and elongation were 401 MPa, 700 MPa, and 36%, respectively. The energy-dispersive spectrometer results showed that the nano-precipitates were rich in Co and Cr elements. Moreover, the crystal-forming behavior and the nanoscale-precipitates-forming mechanism were revealed. Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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| 10. |
- Qin, Gang, et al.
(författare)
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An as-cast high-entropy alloy with remarkable mechanical properties strengthened by nanometer precipitates
- 2020
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Ingår i: Nanoscale. - : ROYAL SOC CHEMISTRY. - 2040-3364 .- 2040-3372. ; 12:6, s. 3965-3976
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Tidskriftsartikel (refereegranskat)abstract
- High-entropy alloys (HEAs) with good ductility and high strength are usually prepared by a combination of forging and heat-treatment processes. In comparison, the as-cast HEAs typically do not reach strengths similar to those of HEAs produced by the forging and heat-treatment processes. Here we report a novel equiatomic-ratio CoCrCuMnNi HEA prepared by vacuum arc melting. We observe that this HEA has excellent mechanical properties, i.e., a yield strength of 458 MPa, and an ultimate tensile strength of 742 MPa with an elongation of 40%. Many nanometer precipitates (5-50 nm in size) and domains (5-10 nm in size) are found in the inter-dendrite and dendrite zones of the produced HEA, which is the key factor for its excellent mechanical properties. The enthalpy of mixing between Cu and Mn, Cr, Co, or Ni is higher than those of mixing between any two of Cr, Co, Ni and Mn, which leads to the separation of Cu from the CoCrCuMnNi HEA. Furthermore, we reveal the nanoscale-precipitate-phase-forming mechanism in the proposed HEA.
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