Several studies were carried out to explore the prognostic role of neutrophil-to-lymphocyte ratio (NLR) in pancreatic cancer, however, with contradictory results. The objectives of this study were to ...summarize the prognostic value of NLR in pancreatic cancer. Embase, PubMed and Cochrane Library were comprehensively retrieved. All the cohort studies focusing on the prognostic value of NLR in pancreatic cancer were eligible. 37 papers containing 43 cohort studies with pancreatic cancer were finally included into this study. The results presented that patients with low NLR might have longer OS when compared to the patients with high NLR (HR = 1.81, 95%CI = 1.59–2.05, P < 0.00001; I2 = 82%). Similar results were detected in the subgroup analyses of OS, which was based on the analysis model, ethnicity, treatment, sample size and cut-off value. In additions, low NLR was significantly associated with longer DFS when compared to high NLR in pancreatic cancer (HR = 1.66, 95%CI = 1.17–2.35, P = 0.005; I2 = 67%). Moreover, patients with low NLR had significantly smaller tumor size (P = 0.0007), better differentiation (P = 0.003), earlier stage (P = 0.02) and low CA-199 level (P = 0.007). In conclusion, it was revealed that low NLR was a favorable predictor of OS and DFS in patients with pancreatic cancer, and NLR is a promising prognostic biomarker for pancreatic cancer.
•Low NLR was obviously associated with longer OS and DFS compared to high NLR in pancreatic cancer.•The association between NLR and clinical parameters was explored.•The relatively large sample size strengthened the convincing of the results.•NLR might be a promising prognostic biomarker for pancreatic cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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•Resistance of HCC cells under the treatment of Sorafenib has been gradually produced.•LncRNA TTN-AS1 functioned as a sponge of miR-16-5p.•Cyclin E1 was targeted by ...miR-16-5p.•Sorafenib resistance in HCC could be regulated by TTN-AS1/miR-16-5p/Cyclin E1 axis via PTEN/Akt pathway.
Drug resistance has always been an important problem affecting the therapeutic effect of hepatocellular carcinoma (HCC). To investigate the potential role of lncRNA TTN-AS1 in HCC cells with sorafenib (SOR) resistance, and explore the underlying pathways, quantitative real time polymerase chain reaction (qRT-PCR) was used to test the expression of TTN-AS1 in HCC tissues and cells. Then, the expression of TTN-AS1 was down-regulated by shRNA, the activity changes, apoptosis and related protein expression in HCC cells with/without SOR treatment were observed in succession. Expression levels of the downstream target of TTN-AS1, miR-16-5p were studied by dual-luciferase binding assay, cell proliferation, and western blotting analysis. Nude mice models of human HCC with TTN-AS1 gene knockdown were established to observe the tumor growth. As the results revealed, TTN-AS1 silencing in HCC cells induced apoptosis by enhancing the sensitivity of cells to SOR, and the tumor in nude mice became smaller. The mechanism study showed that miR-16-5p was affected by TTN-AS1 sponge, up-regulated cyclin E1 expression, and regulated PTEN/Akt signaling pathway, thereby significantly alleviating the inhibition of apoptosis of HCC cells induced by TTN-AS1 gene. Collectively, our results provided TTN-AS1 as a potential therapeutic target for sorafenib resistance in HCC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Pancreatic cancer is a highly malignant gastrointestinal cancer that can widely metastasize during the early stage of disease, and it is associated with one of the worst prognoses among cancers. In ...this study, we aimed to investigate the function of Rho GTPase-activating protein 30 (ARHGAP30) in pancreatic cancer cells and thus propose a novel therapy for pancreatic cancer.
ARHGAP30 expression in tumor tissues from patients with pancreatic cancer as well as cell lines was detected using immunohistochemistry (IHC), real-time polymerase chain reaction, and western blotting. Cell proliferation, transwell, and apoptosis assays were performed and the levels of related proteins were determined after ARHGAP30 knockdown or overexpression. Additionally, in vivo experiments were performed on nude mice.
ARHGAP30 expression was found to be significantly increased in tumor tissues from patients with pancreatic cancer as well as in pancreatic cancer cell lines. IHC and prognostic analyses indicated that patients with high ARHGAP30 expression had a good prognosis. ARHGAP30 overexpression significantly decreased pancreatic cancer cell proliferation and metastasis; promoted apoptosis; reduced β-catenin, B-cell lymphoma 2 (Bcl-2), matrix metalloproteinase-2 (MMP2), and MMP9 expression; and increased Bcl-2-associated X protein (Bax) and cleaved caspase-3 expression. ARHGAP30 knockdown elicited the opposite effects. The effects of ARHGAP30 knockdown were potently attenuated by the β-catenin inhibitor XAV939. ARHGAP30 knockdown-induced RHOA activity was potently attenuated by the RHOA inhibitor CCG1423. In vivo, ARHGAP30 overexpression significantly inhibited lung metastasis in nude mice and increased the survival of mice with lung metastases.
Our findings indicate that ARHGAP30 may function as a tumor suppressor in pancreatic cancer progression by regulating the expression of related genes and the β-catenin pathway.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•A joint learning framework of fully & graph convolutional networks is proposed.•A dynamic superpixel operation is proposed to connect the two networks.•An unsupervised learning strategy is used to ...initialize the networks.•An uncertainty range constraint is added to reduce the effect of inaccurate annotation.
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Tissue/region segmentation of pathology images is essential for quantitative analysis in digital pathology. Previous studies usually require full supervision (e.g., pixel-level annotation) which is challenging to acquire. In this paper, we propose a weakly-supervised model using joint Fully convolutional and Graph convolutional Networks (FGNet) for automated segmentation of pathology images. Instead of using pixel-wise annotations as supervision, we employ an image-level label (i.e., foreground proportion) as weakly-supervised information for training a unified convolutional model. Our FGNet consists of a feature extraction module (with a fully convolutional network) and a classification module (with a graph convolutional network). These two modules are connected via a dynamic superpixel operation, making the joint training possible. To achieve robust segmentation performance, we propose to use mutable numbers of superpixels for both training and inference. Besides, to achieve strict supervision, we employ an uncertainty range constraint in FGNet to reduce the negative effect of inaccurate image-level annotations. Compared with fully-supervised methods, the proposed FGNet achieves competitive segmentation results on three pathology image datasets (i.e., HER2, KI67, and H&E) for cancer region segmentation, suggesting the effectiveness of our method. The code is made publicly available at https://github.com/zhangjun001/FGNet.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
By investigating the migration and invasion ability in pancreatic cancer, this study probed into the lncRNA MALAT1 molecular mechanism on Hippo‐YAP signaling. The expression of lncRNA MALAT1 in PC ...tissues and cells was detected by qRT‐PCR and Western blot. The effect of si‐MALAT1 on proliferation was determined by CCK‐8 assay. Cell apoptosis, migration, and invasion were respectively detected by flow cytometry assay, wound healing assay, and transwell assay. Western blot and immunohistochemistry were successively used for detecting LATS1 and YAP1 expression in pancreatic cancer tissues. The microarray analysis determined that lncRNA MALAT1 in pancreatic cancer was highly expressed. LncRNA MALAT1 presented an extremely high expression level in pancreatic cancer tissues and cells. After transfected with si‐MALAT1, the proliferation of AsPC‐1 cells decreased, induce apoptosis of AsPC‐1 cells, and migration and invasion ability were reduced. The tendency of LATS1 expression level was down‐regulated and YAP1 show the opposite trend in the Hippo‐YAP signaling. The in vivo assay was found that the tumor to be small in size and volume, and the expression of Ki‐67 was decreased. High expression of lncRNA MALAT1 in PC disorder the proliferation, apoptosis, and migration and invasion ability via influence Hippo‐YAP signaling pathway.
By investigating the migration and invasion ability in pancreatic cancer, this study probed into the lncRNA MALAT1 molecular mechanism on Hippo‐YAP signaling. High expression of lncRNA MALAT1 in PC disorder the proliferation, apoptosis, and migration and invasion ability via influence Hippo‐YAP signaling pathway.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
•Engineered exosomes can scavenge a variety of toxic reactive oxygen species using the activity of multiple nanozymes.•Engineered exosomes can target the brain in two ways: actively with targeted ...peptides and passively with photothermal action.•Engineered exosomes reduce microglia activation and mitochondrial damage.
Alzheimer's disease (AD) is one of the leading causes of dementia. The pathogenesis of AD is complex, and oxidative stress, which is involved in neuronal damage through various pathways, is considered to be a central part of AD pathogenesis. Therefore, we took advantage of the blood–brain barrier permeability of biogenic extracellular vesicles to load the high-performance antioxidant resveratrol (Res) and platinum (Pt) nanoparticles with multiple enzymatic activities into the extracellular vesicles and then deliver the ‘Trojan horses’ to the central nervous system to exert synergistic antioxidant effects. In this study, Res-Pt@EVs-RVG was designed to preferentially target the brain using rabies virus glycoprotein (RVG) peptides. In addition, the large photothermal effect of Pt nanoparticles increased the drug penetration and its high blood–brain barrier penetration ability was confirmed in vivo animal experiments. We found through multiple experiments that Res-Pt@EVs-RVG was well absorbed by cells, reduced intracellular reactive oxygen levels, improved mitochondrial damage, and attenuated glial cell activation while reducing neuronal loss in the brains of AD mice and improving memory impairment in APP/PS1 mice. Our results suggest that a biogenic extracellular vesicles-based drug delivery strategy overcomes the disadvantage of poor drug penetration into the central nervous system (CNS) and provides a potential platform for the effective treatment of AD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•F-PCP NPs for rheumatoid arthritis are developed.•F-PCP NPs has obtained excellent photothermal therapy performance.•F-PCP NPs actively target M1 macrophages to reduce its proliferation.
Rheumatoid ...arthritis (RA) is a chronic inflammatory disease characterized by joint hypoxia and the proliferation of M1 macrophages. Therefore, relieving hypoxia and removing M1 macrophages will be a new direction in the treatment of RA. Folic acid (FA)-loaded PCP nanoparticles Fe-Co prussian blue analogue@CeO2@PDA (F-PCP) were used for in situ oxygen (O2) production/chemodynamic/photothermal/treatment of RA. On one hand, PDA-mediated photothermal therapy also has a certain effect on the removal of proliferative M1 macrophages. On the other hand, under the irradiation of NIR laser, F-PCP has obtained excellent photothermal therapy (PTT) performance, which accelerates the Fenton/Fenton-like reaction to produce reactive oxygen species and O2, so as to achieve the chemodynamic therapy (CDT) that inhibits the proliferation of M1 macrophages. It is worth noting that the RA was improved by the synergistic action of CDT and PTT, and the generation of oxygen can alleviate RA hypoxia, which is a means to improve CDT. Therefore, the F-PCP NPs show great potential in improving the therapeutic effect of RA.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Multiple studies have revealed that long non-coding RNA (lncRNAs) served as regulatory factors in modulating tumorigenesis of hepatocellular carcinoma (HCC). In the present study, we demonstrated ...that lncRNA HCP5 was overexpressed in HCC tissues and cell lines, and these findings were obvious even in metastatic and recurrent cases. Knockdown of HCP5 significantly alleviated cell growth, metastasis, and invasion both
in vitro
and
in vivo
through promoting apoptosis and by inactivating the epithelial-mesenchymal transition (EMT) progress. Moreover, miR-29b-3p has been identified as a negatively regulatory target gene of HCP5, and served as a tumor suppressor of HCC to prevent cell proliferation, migration, and invasion. Subsequently, DNMT3A was identified as a downstream regulatory factor of miR-29b-3p, and acted as a participated element of HCC progression by activating AKT phosphorylation. Taken together, our study elucidated for the first time that HCP5 plays a crucial role in HCC via the HCP5/miR-29b-3p/DNMT3A/AKT axis and our findings demonstrated a novel diagnostic and therapeutic strategy with potentiality to treat HCC.
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