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1.
Angew Chem Int Ed Engl ; 63(43): e202409072, 2024 Oct 21.
Article in English | MEDLINE | ID: mdl-39056448

ABSTRACT

Despite numerous studies have reported the inhibition of tin (II) oxidation in mixed tin-lead halide perovskite, there remains a dearth of mechanistic information regarding how tin (II) undergoes oxidation in the precursor solution, particularly in terms of the involvement of DMSO. We here take advantage of density functional theory (DFT) to uncover that SnI2 can coordinate with DMSO and react with singlet oxygen, resulting in the generation of Sn (IV). Moreover, our DFT simulations reveal that benzaldehyde oxime (BZHO) competes with SnI2 in reacting with oxygen through the Alder-ene reaction, hence effectively restraining the oxidation of tin (II), which is further verified by several experimental characterizations. Besides, the introduction of BZHO has also regulated the crystallization of the perovskite film and modified the electronic structure of the perovskite surface. As a result, the perovskite solar cells with the addition of BZHO demonstrate superior performance and operational stability, retaining 82 % of the initial PCE under continuous 1-sun illumination for 800 hours. Furthermore, the efficiency of all-perovskite tandem solar cells treated with BZHO reached 26.76 %. Therefore, this work presents a promising strategy for designing high-performance and stable all-perovskite tandem solar cells.

2.
Angew Chem Int Ed Engl ; : e202201209, 2022 Mar 25.
Article in English | MEDLINE | ID: mdl-35332979

ABSTRACT

An organic small molecule, 1-bromo-4-(methylsulfinyl)benzene (BBMS), was utilized to reduce the energy disorder of a Sn-Pb alloyed perovskite film via hydrogen bonding and coordination bonding interactions, and the resultant BBMS-treated device showed a high efficiency of over 22 % as well as outstanding long-term stability.

3.
Cytokine ; 138: 155397, 2021 02.
Article in English | MEDLINE | ID: mdl-33341002

ABSTRACT

Systemic juvenile idiopathic arthritis (sJIA) is a common chronic disease occurring in children. Increasing studies have demonstrated that long noncoding RNAs (lncRNAs) play important roles in the pathogenesis of diverse human diseases. This study aimed to explore the role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and its mechanism in sJIA. We found that the expression of MALAT1, the plasma level of pro-inflammatory cytokines (IL-6, IL-17, IL-1ß, and TNF-α) as well as MMP-8 and MMP-9 production were significantly elevated in sJIA patients. Moreover, we observed that the production of these cytokines in peripheral blood mononuclear cells (PBMCs) from sJIA patients were reduced after MALAT1 knockdown. Furthermore, bioinformatics analysis predicted that MALAT1 might bind to miR-150-5p and ZBTB4 was a downstream target gene of miR-150-5p. Besides, rescue assays revealed that MALAT1 knockdown-mediated suppressive effects on cytokine production could be reversed by ZBTB4 overexpression. In addition, MALAT1 activated the JAK/STAT signaling by upregulating ZBTB4 expression. In summary, our findings demonstrated that MALAT1 promoted pro-inflammatory cytokine and MMP production by targeting the miR-150-5p/ZBTB4 axis through JAK/STAT signaling pathway in sJIA, suggesting that MALAT1 may have a potential diagnostic biomarker for the pathogenesis and therapy of sJIA.


Subject(s)
Arthritis, Juvenile/metabolism , Cytokines/metabolism , Gene Expression Regulation , Janus Kinase 1/metabolism , MicroRNAs/metabolism , RNA, Long Noncoding/metabolism , STAT1 Transcription Factor/metabolism , Biomarkers/metabolism , Case-Control Studies , Child , Female , Humans , Inflammation , Leukocytes, Mononuclear/metabolism , Male , MicroRNAs/genetics , Repressor Proteins/metabolism , Signal Transduction , Up-Regulation
4.
Sensors (Basel) ; 21(13)2021 Jul 01.
Article in English | MEDLINE | ID: mdl-34283094

ABSTRACT

Target recognition is one of the most challenging tasks in synthetic aperture radar (SAR) image processing since it is highly affected by a series of pre-processing techniques which usually require sophisticated manipulation for different data and consume huge calculation resources. To alleviate this limitation, numerous deep-learning based target recognition methods are proposed, particularly combined with convolutional neural network (CNN) due to its strong capability of data abstraction and end-to-end structure. In this case, although complex pre-processing can be avoided, the inner mechanism of CNN is still unclear. Such a "black box" only tells a result but not what CNN learned from the input data, thus it is difficult for researchers to further analyze the causes of errors. Layer-wise relevance propagation (LRP) is a prevalent pixel-level rearrangement algorithm to visualize neural networks' inner mechanism. LRP is usually applied in sparse auto-encoder with only fully-connected layers rather than CNN, but such network structure usually obtains much lower recognition accuracy than CNN. In this paper, we propose a novel LRP algorithm particularly designed for understanding CNN's performance on SAR image target recognition. We provide a concise form of the correlation between output of a layer and weights of the next layer in CNNs. The proposed method can provide positive and negative contributions in input SAR images for CNN's classification, viewed as a clear visual understanding of CNN's recognition mechanism. Numerous experimental results demonstrate the proposed method outperforms common LRP.


Subject(s)
Neural Networks, Computer , Radar , Algorithms , Image Processing, Computer-Assisted
5.
Angew Chem Int Ed Engl ; 60(32): 17356-17361, 2021 Aug 02.
Article in English | MEDLINE | ID: mdl-34081389

ABSTRACT

Molecular doping is an of significance approach to reduce defects density of perovskite and to improve interfacial charge extraction in perovskite solar cells. Here, we show a new strategy for chemical doping of perovskite via an organic small molecule, which features a fused tricyclic core, showing strong intermolecular π-Pb2+ interactions with under-coordinated Pb2+ in perovskite. This π-Pb2+ interactions could reduce defects density of the perovskite and suppress the nonradiative recombination, which was also confirmed by the density functional theory calculations. In addition, this doping via π-Pb2+ interactions could deepen the surface potential and downshift the work function of the doped perovskite film, facilitating the hole extraction to hole transport layer. As a result, the doped device showed high efficiency of 21.41 % with ignorable hysteresis. This strategy of fused tricyclic core-based doping provides a new perspective for the design of new organic materials to improve the device performance.

6.
Org Biomol Chem ; 17(13): 3356-3360, 2019 03 27.
Article in English | MEDLINE | ID: mdl-30865754

ABSTRACT

A novel HTIB-promoted direct intramolecular dehydrogenative C-S bond coupling reaction of thioamides has been developed to provide 1,3-benzothiazine derivatives in good yields. The reaction proceeds smoothly to reach completion at room temperature within 1 min under metal-free conditions. This protocol provides a mild and efficient strategy for the synthesis of six-membered N,S-containing heterocycles. Preliminary mechanistic studies indicate that a spirocyclic intermediate might be involved.

7.
BMC Complement Altern Med ; 19(1): 156, 2019 Jul 03.
Article in English | MEDLINE | ID: mdl-31269941

ABSTRACT

BACKGROUND: The traditional Chinese medicine prescription, Qianggan formula have been confirmed to be effective on non-alcoholic steatohepatitis (NASH), however, the underlying molecular mechanisms remain obscure. METHODS: Thirty-six male C57BL/6 mice were randomly divided into three groups: normal chow diet group; methionine-and-choline-deficient diet (MCD) group, and Qianggan extract (QG) intervention group (0.4 g/kg daily) that fed with MCD. The efficacy of QG was biochemically and histologically evaluated. The expression profiles of messenger ribonucleic acids (mRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) were examined using microarray and verified by RT-qPCR. RESULTS: QG significantly improved the phenotypic characteristics of NASH, as serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) levels and liver inflammatory cytokines were significantly decreased. By the cutoff of a 1.5-fold change and P < 0.05, 6193 mRNAs, 5692 lncRNAs and 4843 circRNAs were identified as differentially expressed between the MCD and normal groups, and 514 mRNAs, 1182 lncRNAs and 443 circRNAs were identified as differentially expressed between the QG and MCD groups. The intersections (244 mRNAs, 259 lncRNAs and 98 circRNAs) among the three groups were chosen for analysis. Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment revealed that most overlapping mRNAs were related to immune functions such as natural-killer-cell-mediated cytotoxicity, intestinal immune network for IgA production, and T cell receptor signaling pathway. Pathway interactions, protein-protein interactions and molecular complex detection (MCODE) analysis identified numerous immune-related hub genes e.g. natural cytotoxicity triggering receptor 1(Ncr1), C-X-C motif chemokine ligand 9 (Cxcl9), Klra1, and Cd28. Finally, two lncRNAs (Sngh1 and Slc36a3os) and four circRNAs (circ_0009029, circ_0004572, circ_0009212 and circ_0009453) in competing endogenous RNA (ceRNA) networks were constructed by Cytoscape, and immune-related mRNAs (e.g., Cd28, Cd8a, Il15, and Klrk1) were involved in the ceRNA networks. CONCLUSIONS: LncRNA and circRNA-associated immune ceRNA networks might be the targets of QG in alleviating NASH, and our work may provide valuable clues for exploring the mechanisms underlying the effect of QG.


Subject(s)
Drugs, Chinese Herbal/therapeutic use , Non-alcoholic Fatty Liver Disease/drug therapy , Phytotherapy , Animals , Drug Evaluation, Preclinical , Drugs, Chinese Herbal/pharmacology , Male , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/metabolism , Protein Interaction Maps , RNA, Long Noncoding/metabolism , RNA, Messenger/metabolism , Random Allocation
8.
Sensors (Basel) ; 18(10)2018 Oct 01.
Article in English | MEDLINE | ID: mdl-30275407

ABSTRACT

Different from microwave radar, laser radar could be more sensitive to the micro-Doppler (m-D) effect due to its wave length. This limits the application of conventional methods, such as time⁻frequency based approach, since the processing needs a receiver with much higher sampling frequency than microwave radar. In this paper, a micro-Doppler feature extraction algorithm is proposed for the inverse synthetic aperture imaging laser radar (ISAIL). Singular-spectrum analysis (SSA) is employed for separation and reconstruction of the micro-Doppler and rigid body signal. Clear ISAIL image is obtained by minimum entropy criteria after echo signal decomposition. After theoretical derivation, the computation efficiency and ability of the proposed method is proved by the results of simulation and real data of An-26.

9.
Pak J Pharm Sci ; 31(4(Special)): 1761-1766, 2018 Jul.
Article in English | MEDLINE | ID: mdl-30203776

ABSTRACT

Recent studies have shown that statins can inhibit the apoptosis of vascular endothelial cells. Many pharmacological actions of statins have nothing to do with their cholesterol lowering effects. These effects are called non lipid lowering cardiovascular protective effects. In this study, by establishing a high glucose induced vascular endothelial cell apoptosis model, we explored the mechanism of the non lipid - related cardiovascular protective effect of atorvastatin. The results showed that atorvastatin could protect human umbilical vein endothelial cells from damage induced by new high glucose and inhibit apoptosis. High concentration atorvastatin can up regulate the expression of Bcl-2 and down regulate the expression of Bax protein (P<0.05). This suggests that statins may play a role in cardiovascular protection by inhibiting endothelial cell apoptosis. This result is confirmed by experiments, which can provide clues for clinical treatment, and combine drug therapy and lifestyle intervention to reduce blood sugar.


Subject(s)
Apoptosis/drug effects , Atorvastatin/pharmacology , Human Umbilical Vein Endothelial Cells/drug effects , Cell Survival/drug effects , Cells, Cultured , Down-Regulation , Glucose/toxicity , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Proto-Oncogene Proteins c-bcl-2/metabolism , Up-Regulation , bcl-2-Associated X Protein/metabolism
10.
Zhongguo Dang Dai Er Ke Za Zhi ; 16(9): 901-4, 2014 Sep.
Article in Zh | MEDLINE | ID: mdl-25229956

ABSTRACT

OBJECTIVE: To study the efficacy of short-term educational intervention for parents of preschool children with anxiety. METHODS: Forty-nine children with Spence Preschool Anxiety Scale (SPAS) scores of ≥ 48 were randomly divided into intervention and control groups. The children's parents in the intervention group received a collective curriculum on children's anxiety management six times, while the control group was only followed up. All children were evaluated for anxiety by the SPAS 3 and 6 months later, and then the results were compared between the two groups. RESULTS: The test was completed in 21 cases of the intervention group and 22 cases of the control group. At month 3, the intervention group had a significantly lower percentage of children with SPAS scores of ≥ 48 than the control group (62% vs 91%; P<0.05), and this percentage was also significantly lower in the intervention group than in the control group at month 6 (52% vs 82%; P<0.05). At month 3, the intervention group had a significantly reduced mean SPAS score, which was significantly lower than that of the control group (69 ± 12 vs 81 ± 12; P<0.01). At month 6, both groups showed significant decreases in SPAS score, but still the SPAS score was significantly lower in the intervention group than in the control group (65 ± 13 vs 78 ± 13; P<0.01). CONCLUSIONS: Early short-term education for parents can relieve their preschool children's anxiety effectively, but the long-term effect needs to be evaluated by follow-up.


Subject(s)
Anxiety/therapy , Parents/education , Child, Preschool , Female , Humans , Male , Psychiatric Status Rating Scales
11.
Pharmaceuticals (Basel) ; 17(7)2024 Jul 05.
Article in English | MEDLINE | ID: mdl-39065745

ABSTRACT

Inulin may be a promising therapeutic molecule for treating non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms of its therapeutic activity remain unclear. To address this issue, a high-fat-diet-induced NAFLD mouse model was developed and treated with inulin. The NAFLD phenotype was evaluated via histopathological analysis and biochemical parameters, including serum levels of alanine aminotransferase, aspartate aminotransferase, liver triglycerides, etc. A serum metabolomics study was conducted using ultra-performance liquid chromatography coupled with tandem mass spectrometry. The results revealed that inulin mitigated NAFLD symptoms such as histopathological changes and liver cholesterol levels. Through the serum metabolomics study, 347 differential metabolites were identified between the model and control groups, and 139 differential metabolites were identified between the inulin and model groups. Additionally, 48 differential metabolites (such as phosphatidylserine, dihomo-γ-linolenic acid, L-carnitine, and 13-HODE) were identified as candidate targets of inulin and subjected to pathway enrichment analysis. The results revealed that these 48 differential metabolites were enriched in several metabolic pathways such as fatty acid biosynthesis and cardiolipin biosynthesis. Taken together, our results suggest that inulin might attenuate NAFLD partially by modulating 48 differential metabolites and their correlated metabolic pathways, constituting information that might help us find novel therapies for NAFLD.

12.
Neural Netw ; 180: 106634, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39191125

ABSTRACT

Explainable artificial intelligence (XAI) holds significant importance in enhancing the reliability and transparency of network decision-making. SHapley Additive exPlanations (SHAP) is a game-theoretic approach for network interpretation, attributing confidence to inputs features to measure their importance. However, SHAP often relies on a flawed assumption that the model's features are independent, leading to incorrect results when dealing with correlated features. In this paper, we introduce a novel manifold-based Shapley explanation method, termed Latent SHAP. Latent SHAP transforms high-dimensional data into low-dimensional manifolds to capture correlations among features. We compute Shapley values on the data manifold and devise three distinct gradient-based mapping methods to transfer them back to the high-dimensional space. Our primary objectives include: (1) correcting misinterpretations by SHAP in certain samples; (2) addressing the challenge of feature correlations in high-dimensional data interpretation; and (3) reducing algorithmic complexity through Manifold SHAP for application in complex network interpretations. Code is available at https://github.com/Teriri1999/Latent-SHAP.

13.
Arch Esp Urol ; 77(8): 889-896, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39385484

ABSTRACT

BACKGROUND: Prostate cancer is a remarkable global health concern, necessitating accurate risk stratification for optimal treatment and outcome prediction. By highlighting the potential of imaging-based approaches to improve risk assessment in prostate cancer, this research aims to evaluate the diagnostic efficacy of the Prostate Imaging Reporting and Data System (PI-RADS) v2.1 combined with apparent diffusion coefficient (ADC) values to gain increased context within the broad landscape of clinical needs and advancements in prostate cancer management. METHODS: The clinical data of 145 patients diagnosed with prostate cancer were retrospectively analysed. The patients were divided into low-moderate- and high-risk groups on the basis of Gleason scores. PI-RADS v2.1 scores were assessed by senior radiologists and ADC values were calculated by using diffusion-weighted imaging. Statistical, univariate logistic regression, and receiver operating characteristic curve analyses were employed to evaluate the diagnostic efficacy of each index and combined PI-RADS v2.1 scores and ADC values. RESULTS: This study found significant differences in PI-RADS v2.1 scores and ADC values between the low-moderate- and high-risk groups (p < 0.001). Logistic regression analysis revealed associations of various clinical indicators, PI-RADS score and ADC values with Gleason risk classification. Amongst indices, mean ADC demonstrated the highest sensitivity (0.912) and area under curve (AUC) value (0.962) and the combination of PI-RADS v2.1 with mean ADC showed high predictive value for the Gleason risk grading of prostate cancer with a high AUC value (0.966). CONCLUSIONS: This study provides valuable evidence for the potential utility of imaging-based approaches, specifically PI-RADS v2.1 combined with ADC values, in enhancing the accuracy of risk stratification in prostate cancer.


Subject(s)
Neoplasm Grading , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/diagnosis , Retrospective Studies , Aged , Middle Aged , Risk Assessment , Diffusion Magnetic Resonance Imaging/methods
14.
Neural Netw ; 178: 106473, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38941740

ABSTRACT

Despite the tremendous success of convolutional neural networks (CNNs) in computer vision, the mechanism of CNNs still lacks clear interpretation. Currently, class activation mapping (CAM), a famous visualization technique to interpret CNN's decision, has drawn increasing attention. Gradient-based CAMs are efficient, while the performance is heavily affected by gradient vanishing and exploding. In contrast, gradient-free CAMs can avoid computing gradients to produce more understandable results. However, they are quite time-consuming because hundreds of forward interference per image are required. In this paper, we proposed Cluster-CAM, an effective and efficient gradient-free CNN interpretation algorithm. Cluster-CAM can significantly reduce the times of forward propagation by splitting the feature maps into clusters. Furthermore, we propose an artful strategy to forge a cognition-base map and cognition-scissors from clustered feature maps. The final salience heatmap will be produced by merging the above cognition maps. Qualitative results conspicuously show that Cluster-CAM can produce heatmaps where the highlighted regions match the human's cognition more precisely than existing CAMs. The quantitative evaluation further demonstrates the superiority of Cluster-CAM in both effectiveness and efficiency.


Subject(s)
Algorithms , Neural Networks, Computer , Humans , Cluster Analysis , Image Processing, Computer-Assisted/methods , Cognition/physiology
15.
Neural Netw ; 165: 982-986, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37467585

ABSTRACT

Synthetic aperture radar (SAR) automatic target recognition (ATR) is a crucial technique utilized in various scenarios of geoscience and remote sensing. Despite the remarkable success of convolutional neural networks (CNNs) in optical vision tasks, the application of CNNs in SAR ATR is still a challenging area due to the significant differences in the imaging mechanisms of SAR and optical images. This paper analytically addresses the cognitive gap of CNNs between optical and SAR images by leveraging multi-order interactions to measure their representation capacity. Furthermore, we propose a subjective evaluation strategy to compare human interactions with those of CNNs. Our findings reveal that CNNs operate differently for optical and SAR images. Specifically, for SAR images, CNNs' representation capacity is comparable to that of humans, as they can encode intermediate interactions better than simple and complex ones. In contrast, for optical images, CNNs excel at encoding simple and complex interactions, but not intermediate interactions.


Subject(s)
Neural Networks, Computer , Radar , Humans , Cognition
16.
Front Cell Infect Microbiol ; 13: 1066053, 2023.
Article in English | MEDLINE | ID: mdl-36779187

ABSTRACT

Background: Lingguizhugan decoction is a traditional Chinese medicine prescription that has been used to improve non-alcoholic fatty liver disease and its progressive form, non-alcoholic steatohepatitis (NASH). However, the anti-NASH effects and underlying mechanisms of Lingguizhugan decoction remain unclear. Methods: Male Sprague-Dawley rats were fed a methionine- and choline-deficient (MCD) diet to induce NASH, and then given Lingguizhugan decoction orally for four weeks. NASH indexes were evaluated by histopathological analysis and biochemical parameters including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver triglycerides (TG), etc. Fecal samples of rats were subjected to profile the changes of gut microbiota and metabolites using 16S rRNA sequencing and ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS). Bioinformatics was used to identify Lingguizhugan decoction reversed candidates, and Spearman's correlation analysis was performed to uncover the relationship among gut microbiota, fecal metabolites, and NASH indexes. Results: Four-week Lingguizhugan decoction treatment ameliorated MCD diet-induced NASH features, as evidenced by improved hepatic steatosis and inflammation, as well as decreased serum AST and ALT levels. Besides, Lingguizhugan decoction partially restored the changes in gut microbial community composition in NASH rats. Meanwhile, the relative abundance of 26 genera was significantly changed in NASH rats, and 11 genera (such as odoribacter, Ruminococcus_1, Ruminococcaceae_UCG-004, etc.) were identified as significantly reversed by Lingguizhugan decoction. Additionally, a total of 99 metabolites were significantly altered in NASH rats, and 57 metabolites (such as TDCA, Glutamic acid, Isocaproic acid, etc.) enriched in different pathways were reversed by Lingguizhugan decoction. Furthermore, Spearman's correlation analyses revealed that most of the 57 metabolites were significantly correlated with 11 genera and NASH indexes. Conclusion: Lingguizhugan decoction may exert protective effects on NASH partially by modulating gut microbiota and correlated metabolites.


Subject(s)
Gastrointestinal Microbiome , Non-alcoholic Fatty Liver Disease , Tandem Mass Spectrometry , Animals , Male , Mice , Rats , Choline/metabolism , Choline/pharmacology , Chromatography, Liquid , Liver/pathology , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Rats, Sprague-Dawley , RNA, Ribosomal, 16S/genetics , Drugs, Chinese Herbal/pharmacology
17.
J Exp Clin Cancer Res ; 41(1): 19, 2022 Jan 10.
Article in English | MEDLINE | ID: mdl-35012593

ABSTRACT

BACKGROUND: Colorectal carcinoma (CRC) is the third most common cancer and second most common cause of cancer-related deaths worldwide. Ribonucleic acid (RNA) N6-methyladnosine (m6A) and methyltransferase-like 3 (METTL3) play key roles in cancer progression. However, the roles of m6A and METTL3 in CRC progression require further clarification. METHODS: Adenoma and CRC samples were examined to detect m6A and METTL3 levels, and tissue microarrays were performed to evaluate the association of m6A and METTL3 levels with the survival of patients with CRC. The biological functions of METTL3 were investigated through cell counting kit-8, wound healing, and transwell assays. M6A epitranscriptomic microarray, methylated RNA immunoprecipitation-qPCR, RNA stability, luciferase reporter, and RNA immunoprecipitation assays were performed to explore the mechanism of METTL3 in CRC progression. RESULTS: M6A and METTL3 levels were substantially elevated in CRC tissues, and patients with CRC with a high m6A or METTL3 levels exhibited shorter overall survival. METTL3 knockdown substantially inhibited the proliferation, migration, and invasion of CRC cells. An m6A epitranscriptomic microarray revealed that the cell polarity regulator Crumbs3 (CRB3) was the downstream target of METTL3. METTL3 knockdown substantially reduced the m6A level of CRB3, and inhibited the degradation of CRB3 mRNA to increase CRB3 expression. Luciferase reporter assays also showed that the transcriptional level of wild-type CRB3 significantly increased after METTL3 knockdown but not its level of variation. Knockdown of YT521-B homology domain-containing family protein 2 (YTHDF2) substantially increased CRB3 expression. RNA immunoprecipitation assays also verified the direct interaction between the YTHDF2 and CRB3 mRNA, and this direct interaction was impaired after METTL3 inhibition. In addition, CRB3 knockdown significantly promoted the proliferation, migration, and invasion of CRC cells. Mechanistically, METTL3 knockdown activated the Hippo pathway and reduced nuclear localization of Yes1-associated transcriptional regulator, and the effects were reversed by CRB3 knockdown. CONCLUSIONS: M6A and METTL3 levels were substantially elevated in CRC tissues relative to normal tissues. Patients with CRC with high m6A or METTL3 levels exhibited shorter overall survival, and METTL3 promoted CRC progression. Mechanistically, METTL3 regulated the progression of CRC by regulating the m6A-CRB3-Hippo pathway.


Subject(s)
Colorectal Neoplasms/genetics , Hippo Signaling Pathway/genetics , Methyltransferases/genetics , Cell Line, Tumor , Cell Proliferation , Colorectal Neoplasms/pathology , Disease Progression , Female , Humans , Male , Neoplasm Invasiveness , Transfection
18.
Biomed Pharmacother ; 143: 112181, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34649337

ABSTRACT

Jiangzhi Granule is a commonly used traditional Chinese medicine for treating non-alcoholic fatty liver disease. However, its key ingredients and underlying mechanisms for attenuating nonalcoholic steatohepatitis (NASH) remain unclear. To address this issue, UPLC-TOF-MS based chemical profiling, network pharmacology and animal experimental validation were employed. First, a total of 56 main ingredients of Jiangzhi Granule and 38 ingredients in the blood and liver (after oral administration) were identified. Then, 170 potential targets of the absorbed ingredients and 50 targets of NASH were identified, and 10 overlapped genes were identified as candidate targets of Jiangzhi Granule for NASH treatment. A Jiangzhi Granule-ingredients-targets-disease network was constructed using Cytoscape software, which included eight main ingredients (such as emodin, resveratrol and quercetin) and 10 candidate targets (such as TNF, IL6 and CCL2). Functional enrichment indicated that the candidate targets were enriched in multiple pathways (such as the TNF signaling pathway). Furthermore, a NASH mice model was constructed and intervened with Jiangzhi Granule. The results revealed that Jiangzhi Granule could ameliorate NASH characteristics, such as histopathological changes and liver cholesterol level. Meanwhile, Jiangzhi Granule significantly decreased the mRNA and protein expression of TNFα in NASH mice liver, suppressed NFκB activation, and inhibited the expression of macrophage activation marker F4/80 and M1-type polarization marker CD11b/CD11c. ELISA assay indicated that Jiangzhi Granule reduced pro-inflammatory cytokines (including TNFα, IL-1ß and IL-6) in the liver. Collectively, our results suggested that Jiangzhi Granule could attenuate NASH by suppressing TNF/NFκB signaling mediated macrophage M1-type polarization.


Subject(s)
Drugs, Chinese Herbal/pharmacology , Liver/drug effects , Macrophages/drug effects , NF-kappa B/metabolism , Network Pharmacology , Non-alcoholic Fatty Liver Disease/prevention & control , Phytochemicals/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Animals , Chromatography, High Pressure Liquid , Disease Models, Animal , Liver/immunology , Liver/metabolism , Liver/pathology , Macrophages/immunology , Macrophages/metabolism , Male , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/immunology , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Phenotype , Protein Interaction Maps , Signal Transduction , Spectrometry, Mass, Electrospray Ionization , Tandem Mass Spectrometry
19.
Cancer Manag Res ; 12: 7277-7289, 2020.
Article in English | MEDLINE | ID: mdl-32884343

ABSTRACT

BACKGROUND: Long noncoding RNAs play essential roles in regulating drug resistance in cancers. However, how and whether lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) could mediate cisplatin resistance in ovarian cancer remain poorly understood. PATIENTS AND METHODS: Eighteen cisplatin-sensitive and 19 cisplatin-resistant patients with ovarian cancer were recruited. Cisplatin-resistant ovarian cancer cells were used for this study. The expression levels of NEAT1, microRNA (miR)-770-5p and poly adenosine diphosphate-ribose polymerase 1 (PARP1) were detected by quantitative real-time polymerase chain reaction or Western blot. Cisplatin resistance was assessed by the half-maximal inhibitory concentration (IC50) of cisplatin, cell viability and apoptosis using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide, flow cytometry and Western blot, respectively. The target association between miR-770-5p and NEAT1 or PARP1 was investigated by dual-luciferase reporter assay. The xenograft model was used to investigate cisplatin resistance in vivo. RESULTS: NEAT1 expression is elevated in cisplatin-resistant ovarian cancer tissues and cells. Knockdown of NEAT1 repressed cisplatin resistance by decreasing the IC50 of cisplatin, cell viability and increasing apoptosis. MiR-770-5p was bound to NEAT1 and PARP1 was confirmed as a target of miR-770-5p. MiR-770-5p inhibition or PARP1 restoration could abate the effect of NEAT1 silencing on cisplatin resistance in cisplatin-resistant ovarian cancer cells. Moreover, NEAT1 knockdown reduced PARP1 expression by increasing miR-770-5p. Interference of NEAT1 decreased xenograft tumor growth by regulating miR-770-5p and PARP1. CONCLUSION: Knockdown of NEAT1 inhibited cisplatin resistance in ovarian cancer cells by up-regulating miR-770-5p and down-regulating PARP1, providing a new target for improving the efficacy of cisplatin-based therapy in ovarian cancer.

20.
Medicine (Baltimore) ; 99(33): e21667, 2020 Aug 14.
Article in English | MEDLINE | ID: mdl-32872031

ABSTRACT

BACKGROUND: This study will explore the association between tumor necrosis factor α (TNF-α) and uterine fibroids (UFs). METHODS: We will retrieve electronic databases in Cochrane Library, PUBMED, EMBASE, Web of Science, WANGFANG, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from inception to the present. All potential case-controlled studies investigating the association between TNF-α and UFs will be included in this study. Two researchers will independently select literature, appraise study quality, and extract outcome data. We will utilize a fixed-effects model or a random-effects model to synthesize outcome data. All data analysis will be performed by RevMan 5.3 software. RESULTS: The present study will supply high-quality synthesis and/or descriptive analysis of the recent evidence to explore the association between TNF-α and UFs. CONCLUSION: This study will exert evidence to determine whether or not TNF-α is associated with UFs. STUDY REGISTRATION NUMBER: INPLASY202070010.


Subject(s)
Leiomyoma/metabolism , Tumor Necrosis Factor-alpha/metabolism , Uterine Neoplasms/metabolism , Biomarkers, Tumor , Case-Control Studies , Female , Humans , Systematic Reviews as Topic
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