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1.
Cell ; 186(4): 764-785.e21, 2023 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-36803604

RESUMO

The choroid plexus (ChP) is the blood-cerebrospinal fluid (CSF) barrier and the primary source of CSF. Acquired hydrocephalus, caused by brain infection or hemorrhage, lacks drug treatments due to obscure pathobiology. Our integrated, multi-omic investigation of post-infectious hydrocephalus (PIH) and post-hemorrhagic hydrocephalus (PHH) models revealed that lipopolysaccharide and blood breakdown products trigger highly similar TLR4-dependent immune responses at the ChP-CSF interface. The resulting CSF "cytokine storm", elicited from peripherally derived and border-associated ChP macrophages, causes increased CSF production from ChP epithelial cells via phospho-activation of the TNF-receptor-associated kinase SPAK, which serves as a regulatory scaffold of a multi-ion transporter protein complex. Genetic or pharmacological immunomodulation prevents PIH and PHH by antagonizing SPAK-dependent CSF hypersecretion. These results reveal the ChP as a dynamic, cellularly heterogeneous tissue with highly regulated immune-secretory capacity, expand our understanding of ChP immune-epithelial cell cross talk, and reframe PIH and PHH as related neuroimmune disorders vulnerable to small molecule pharmacotherapy.


Assuntos
Plexo Corióideo , Hidrocefalia , Humanos , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Plexo Corióideo/metabolismo , Hidrocefalia/líquido cefalorraquidiano , Hidrocefalia/imunologia , Imunidade Inata , Síndrome da Liberação de Citocina/patologia
2.
Proteins ; 91(9): 1351-1360, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37163477

RESUMO

Protein glycation can result in the formation of advanced glycation end products (AGEs), which pose a potential health risk due to their association with diabetic complications. Natural products are a source of drugs discovery and the search for potential natural inhibitors of AGEs is of great significance. Glucosinolates (GSLs) mainly from cruciferous plants have potential antioxidant, anti-inflammatory, and anti-glycation activities. In this study, the inhibitory activity of GSLs on bovine serum albumin (BSA) along with its mechanism was investigated by virtual screening and various computational simulation techniques. Virtual screening revealed that 174 GSLs were screened using Maestro based on the glide score and 89% of the compounds were found to have potential anti-glycation ability with the docking scores less than -5 kcal/mol. Molecular docking showed that the top 10 GSLs were bound to the IIA structural domain of BSA. Among them, glucohesperin (1) and 2-hydroxyethyl glucosinolate (2) had the lowest docking scores of -9.428 and -9.333 kcal/mol, respectively, reflecting their good binding affinity. Molecular dynamics simulations of 1 (ΔG = -43.46 kcal/mol) and 2 (ΔG = -43.71 kcal/mol) revealed that the complexes of these two compounds with proteins had good stability. Further binding site analysis suggested that the mechanism of inhibition of protein glycation by these two active ingredients might be through competitive hydrogen bonding to maintain the structural integrity of the protein, thus inhibiting glycation reaction. Moreover, the ADMET values and CYP450 metabolism prediction data were within the recommended values. Therefore, it can be concluded that 1 and 2 may act as potential anti-glycation agents.


Assuntos
Glucosinolatos , Simulação de Dinâmica Molecular , Simulação de Acoplamento Molecular , Agentes Antiglicação , Produtos Finais de Glicação Avançada
3.
Br J Cancer ; 128(8): 1466-1477, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36759726

RESUMO

BACKGROUND: The clinical significance and immune correlation of CD103+ cells in prostate cancer (PCa) remain explored. METHODS: In total, 1080 patients with PCa underwent radical prostatectomy from three cohorts were enrolled for retrospective analysis. Tumour microarrays were constructed and fresh tumour samples were analysed by flow cytometry. RESULTS: High CD103+ cell infiltration correlated with reduced biochemical recurrence (BCR)-free survival in PCa. Adjuvant hormone therapy (HT) prolonged the BCR-free survival for high-risk node-negative diseases with CD103+ cell abundance. CD103+ cell infiltration correlated with less cytotoxic expression and increased infiltration of CD8+ and CD4+ T cells, M1 macrophages and mast cells in PCa. Intratumoral CD8+ T cell was the predominant source of CD103, and the CD103+ subset of CD8+ T cells was featured with high IL-10, PD-1 and CTLA-4 expression. Tumour-infiltrating CD103+ CD8+ T cells exerted anti-tumour function when treated with HT ex vivo. DISCUSSION: CD103+ cell infiltration predicted BCR-free survival and response to adjuvant HT in PCa. CD103+ cell infiltration correlated with an enriched but immune-evasive immune landscape. The study supported a model that CD103 expression conferred negative prognostic impact and immunosuppressive function to tumour-infiltrating CD8+ T cells, while the CD103+ CD8+ T cells exhibited a powerful anti-tumour immunity with response to HT.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias da Próstata , Humanos , Masculino , Cadeias alfa de Integrinas , Linfócitos do Interstício Tumoral , Prevalência , Prognóstico , Neoplasias da Próstata/terapia , Neoplasias da Próstata/metabolismo , Estudos Retrospectivos
4.
Mol Ther ; 30(3): 1054-1070, 2022 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-35038580

RESUMO

Circular RNAs (circRNAs) play critical roles in different diseases. Exosomes are important intermediates of intercellular communication. While both have been widely reported in cancers, exosome-derived circRNAs are rarely studied. In this work, we identified the differently expressed circRNAs in bladder cancer (BCa) tissue and exosomes through high-throughput sequencing. RNA pull-down, RNA immunoprecipitation, and luciferase reporter assays were used to investigate the interactions between specific circRNAs, microRNAs (miRNAs), and mRNAs. Wound-healing, Transwell, Cell Counting Kit-8 (CCK8), and colony-formation assays were used to study the biological roles in vitro. Metabolomics were used to explore the mechanism of how specific circRNAs influenced BCa cell behavior. Flow cytometry was used to study how specific circRNAs affected the function of CD8+ T cells in tumor microenvironments. We identified that exosome-derived hsa_circ_0085361 (circTRPS1) was correlated with aggressive phenotypes of BCa cells via sponging miR-141-3p. Metabolomics and RNA sequencing (RNA-seq) identified GLS1-mediated glutamine metabolism was involved in circTRPS1-mediated alterations. Exosomes derived from circTRPS1 knocked down BCa cells, prevented CD8+ T cells from exhaustion, and repressed the malignant phenotype of BCa cells. In conclusion, exosome-derived circTRPS1 from BCa cells can modulate the intracellular reactive oxygen species (ROS) balance and CD8+ T cell exhaustion via the circTRPS1/miR141-3p/GLS1 axis. Our work may provide a potential biomarker and therapeutic target for BCa.


Assuntos
Exossomos , MicroRNAs , Neoplasias , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Exossomos/genética , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/genética , Fenótipo , RNA Circular/genética , Microambiente Tumoral/genética , Bexiga Urinária/metabolismo
5.
Cancer Sci ; 113(11): 3698-3709, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36018546

RESUMO

Recent studies identified Midkine (MDK) as playing a key role in immune regulation. In this study, we aimed to discover the clinical significance and translational relevance in prostate cancer (PCa). We retrospectively analyzed 759 PCa patients who underwent radical prostatectomy from Huashan Hospital, Fudan University (training cohort, n = 369) and Chinese Prostate Cancer Consortium (validation cohort, n = 390). A total of 325 PCa patients from The Cancer Genome Atlas (TCGA) database (external cohort) were analyzed for exploration. Immune landscape and antitumor immunity were assessed through immunohistochemistry and flow cytometry. Patient-derived explant culture system was applied for evaluating the targeting potential of MDK. We found that intratumoral MDK expression correlated with PCa progression, which indicated an unfavorable biochemical recurrence (BCR)-free survival for postoperative PCa patients. Addition of MDK expression to the postoperative risk assessment tool CAPRA-S could improve its prognostic value. Tumors with MDK abundance characterized the tumor-infiltrating CD8+ T cells with less cytotoxicity production and increased immune checkpoint expression, which were accompanied by enriched immunosuppressive contexture. Moreover, MDK inhibition could reactivate CD8+ T cell antitumor immunity. MDK mRNA expression negatively correlated with androgen receptor activity signature and positively associated with radiotherapy-related signature. In conclusion, intratumoral MDK expression could serve as an independent prognosticator for BCR in postoperative PCa patients. MDK expression impaired the antitumor function of CD8+ T cells through orchestrating an immunoevasive microenvironment, which could be reversed by MDK inhibition. Moreover, tumors with MDK enrichment possessed potential sensitivity to postoperative radiotherapy while resistance to adjuvant hormonal therapy of PCa. MDK could be considered as a potential therapeutic target for PCa.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias da Próstata , Masculino , Humanos , Midkina , Linfócitos T CD8-Positivos/metabolismo , Estudos Retrospectivos , Prognóstico , Neoplasias da Próstata/patologia , Microambiente Tumoral
6.
Entropy (Basel) ; 24(10)2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37420434

RESUMO

In this paper, we present the multi-stage attentive network (MSAN), an efficient and good generalization performance convolutional neural network (CNN) architecture for motion deblurring. We build a multi-stage encoder-decoder network with self-attention and use the binary cross-entropy loss to train our model. In MSAN, there are two core designs. First, we introduce a new attention-based end-to-end method on top of multi-stage networks, which applies group convolution to the self-attention module, effectively reducing the computing cost and improving the model's adaptability to different blurred images. Secondly, we propose using binary cross-entropy loss instead of pixel loss to optimize our model to minimize the over-smoothing impact of pixel loss while maintaining a good deblurring effect. We conduct extensive experiments on several deblurring datasets to evaluate the performance of our solution for deblurring. Our MSAN achieves superior performance while also generalizing and compares well with state-of-the-art methods.

7.
Cancer Cell Int ; 20: 151, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32398967

RESUMO

BACKGROUND: Circular RNAs (circRNAs) play an essential role in the regulation of gene expression. However, the underlying mechanisms remain unknown. This study aimed to evaluate the role of hsa_circ_0068307 in bladder cancer (BCa). METHODS: Rt-qPCR was used to detect hsa_circ_0068307 expression in BCa cell lines. The CCK8, colony formation, and Transwell assays were used to evaluate the effect of hsa_circ_0068307 on BCa cell migration and proliferation. Bioinformatics and luciferase reporter experiments were used to study the regulatory mechanism. Nude mouse xenografts were generated to examine the effect of hsa_circ_0068307 on tumor growth. RESULTS: The results showed that hsa_circ_0068307 was upregulated in BCa cell lines. Downregulation of hsa_circ_0068307 suppressed cell migration and proliferation in T24 and UMUC3 cells. Hsa_circ_0068307 silencing suppressed cancer stem cell differentiation by upregulating miR-147 expression. Upregulation of miR-147 suppressed c-Myc expression, which is involved in cancer stem cell differentiation. Luciferase reporter assays confirmed that hsa_circ_0068307 upregulated c-Myc expression by targeting miR-147. In vivo studies showed that hsa_circ_0068307 knockdown suppressed T24 tumor growth. CONCLUSIONS: These data indicate that downregulation of hsa_circ_0068307 reversed the stem cell-like properties of human bladder cancer through the regulation of the miR-147/c-Myc axis.

8.
Biomarkers ; 25(3): 260-267, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32141338

RESUMO

Background: The number of patients suffering from coronary heart disease with cancer is rising. There is scarce evidence concerning the biomarkers related to prognosis among patients undergoing percutaneous coronary intervention (PCI) with cancer. Thus, the aim of this study was to investigate the association between red blood cell distribution width (RDW) and prognosis in this population.Methods: A total of 172 patients undergoing PCI with previous history of cancer were enrolled in this retrospective study. The endpoint was long-term all-cause mortality. According to tertiles of RDW, the patients were classified into three groups: Tertile 1 (RDW <12.8%), Tertile 2 (RDW ≥12.8% and <13.5%) and Tertile 3 (RDW ≥13.5%).Results: During an average follow-up period of 33.3 months, 29 deaths occurred. Compared with Tertile 3, mortality of Tertile 1 and Tertile 2 was significantly lower in the Kaplan-Meier analysis. In multivariate Cox regression analysis, RDW remained an independent risk factor of mortality (HR: 1.938, 95% CI: 1.295-2.655, p < 0.001). The all-cause mortality in Tertile 3 was significantly higher than that in Tertile 1 (HR: 5.766; 95% CI: 1.426-23.310, p = 0.014).Conclusions: An elevated RDW level (≥13.5%) was associated with long-term all-cause mortality among patients undergoing PCI with previous history of cancer.


Assuntos
Biomarcadores/sangue , Doença das Coronárias/cirurgia , Índices de Eritrócitos , Eritrócitos/metabolismo , Neoplasias/complicações , Intervenção Coronária Percutânea/métodos , Idoso , Doença das Coronárias/complicações , Doença das Coronárias/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
9.
Entropy (Basel) ; 21(5)2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-33267175

RESUMO

A novel adaptive secure holographic image watermarking method in the sharp frequency localized contourlet transform (SFLCT) domain is presented. Based upon the sine logistic modulation map and the logistic map, we develop an encrypted binary computer-generated hologram technique to fabricate a hologram of a watermark first. Owing to the enormous key space of the encrypted hologram, the security of the image watermarking system is increased. Then the hologram watermark is embedded into the SFLCT coefficients with Schur decomposition. To obtain better imperceptibility and robustness, the entropy and the edge entropy are utilized to select the suitable watermark embedding positions adaptively. Compared with other watermarking schemes, the suggested method provides a better performance with respect to both imperceptibility and robustness. Experiments show that our watermarking scheme for images is not only is secure and invisible, but also has a stronger robustness against different kinds of attack.

11.
Sensors (Basel) ; 18(7)2018 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-29966321

RESUMO

Fault diagnosis of rolling element bearings is an effective technology to ensure the steadiness of rotating machineries. Most of the existing fault diagnosis algorithms are supervised methods and generally require sufficient labeled data for training. However, the acquisition of labeled samples is often laborious and costly in practice, whereas there are abundant unlabeled samples which also imply health information of bearings. Thus, it is worthwhile to develop semi-supervised methods of fault diagnosis to make effective use of the plentiful unlabeled samples. Nevertheless, considering the normal data are much more than the faulty ones, the problem of imbalanced data exists among unlabeled samples for fault diagnosis. Besides, in practice, bearings often work under uncertain and variable operation conditions, which would also have negative influence on fault diagnosis. To solve these issues, a novel hybrid method for bearing fault diagnosis is proposed in this paper: (1) Inspired by visibility graph, a novel fault feature extraction method named visibility graph feature (VGF) is proposed. The obtained features by VGF are natively insensitive to variable conditions, which has been validated by a simulation experiment in this paper; (2) On basis of VGF, to deal with imbalanced unlabeled data, graph-based rebalance semi-supervised learning (GRSSL) for fault diagnosis is proposed. In GRSSL, a graph based on a weighted sparse adjacency matrix is constructed by the k-nearest neighbors and Gaussian Kernel weighting algorithm by means of the samples. Then, a bivariate cost function over classification and normalized label variable is built up to rebalance the importance of labels. Finally, the proposed VGF-GRSSL method was verified by data collected from Case Western Reserve University Bearing Data Center. The experiment results show that the proposed method of bearing fault diagnosis performs effectively to deal with the imbalanced unlabeled data under variable conditions.

12.
Sensors (Basel) ; 19(1)2018 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-30577670

RESUMO

Bearings are vital components in industrial machines. Diagnosing the fault of rolling element bearings and ensuring normal operation is essential. However, the faults of rolling element bearings under variable conditions and the adaptive feature selection has rarely been discussed until now. Thus, it is essential to develop a practicable method to put forward the disposal of the fault under variable conditions. Considering these issues, this paper uses the method based on the Mahalanobis Taguchi System (MTS), and overcomes two shortcomings of MTS: (1) MTS is an effective tool to classify faults and has strong robustness to operating conditions, but it can only handle binary classification problems, and this paper constructs the multiclass measurement scale to deal with multi-classification problems. (2) MTS can determine important features, but uses the hard threshold to select the features, and this paper selects the proper feature sequence instead of the threshold to overcome the lesser adaptivity of the threshold configuration for signal-to-noise gain. Hence, this method proposes a novel method named adaptive Multiclass Mahalanobis Taguchi system (aMMTS), in conjunction with variational mode decomposition (VMD) and singular value decomposition (SVD), and is employed to diagnose the faults under the variable conditions. Finally, this method is verified by using the signal data collected from Case Western Reserve University Bearing Data Center. The result shows that it is accurate for bearings fault diagnosis under variable conditions.

13.
Sci Rep ; 14(1): 1111, 2024 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212659

RESUMO

As a generalization of the optimal mass transport (OMT) approach of Benamou and Brenier's, the regularized optimal mass transport (rOMT) formulates a transport problem from an initial mass configuration to another with the optimality defined by the total kinetic energy, but subject to an advection-diffusion constraint equation. Both rOMT and the Benamou and Brenier's formulation require the total initial and final masses to be equal; mass is preserved during the entire transport process. However, for many applications, e.g., in dynamic image tracking, this constraint is rarely if ever satisfied. Therefore, we propose to employ an unbalanced version of rOMT to remove this constraint together with a detailed numerical solution procedure and applications to analyzing fluid flows in the brain.


Assuntos
Encéfalo , Transporte Biológico , Difusão
14.
J Mater Chem B ; 12(16): 3984-3995, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38563496

RESUMO

The natural extracellular matrix (ECM) consists of a continuous integrated fibrin network and a negatively charged proteoglycan-based matrix. In this work, we report a novel three-dimensional nanofiber hydrogel composite that mimics the natural ECM structure, exhibiting both degradability and mechanical characteristics comparable to that of tumor tissue. The embedded nanofiber improves the hydrogel mechanical properties, and varying the fiber density can match the elastic modulus of different tumor tissues (1.51-10.77 kPa). The degradability of the scaffold gives sufficient space for tumor cells to secrete and remodel the ECM. The expression levels of cancer stem cell markers confirmed the development of aggressive and metastatic phenotypes of prostate cancer cells in the 3D scaffold. Similar results were obtained in terms of anticancer resistance of prostate cancer cells in 3D scaffolds showing stem cell-like properties, suggesting that the current bionic 3D scaffold tumor model has broad potential in the development of effective targeted agents.


Assuntos
Matriz Extracelular , Hidrogéis , Nanofibras , Nanofibras/química , Humanos , Matriz Extracelular/metabolismo , Matriz Extracelular/química , Hidrogéis/química , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Alicerces Teciduais/química , Masculino , Linhagem Celular Tumoral , Células Tumorais Cultivadas , Proliferação de Células/efeitos dos fármacos
15.
Colloids Surf B Biointerfaces ; 241: 114030, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38901267

RESUMO

To enhance the cellular uptake of liposomes, we prepared conventional liposomes with targeting molecules and surface-charged liposomes and evaluated their potential as nano-carriers and vaccine adjuvants by comparing their endocytosis efficiencies using immune cells. Surface-charged liposomes were synthesized via a one-step microfluidic method, which provided a novel, simple, fast, and highly reproducible method for preparing liposomes. Flow cytometry revealed that cationic polyelectrolyte-coated liposomes exhibited higher endocytosis efficiencies (of up to a factor of 100) in A774A.1 cells and JAWs II cells compared with uncoated liposomes or those coated with anionic polyelectrolytes. Positively charged liposomes exhibited some cytotoxicity at quaternary-chitosan coating concentrations higher than 6 mg/mL; however, significantly lower cytotoxicities (by a factor of almost ten) were obtained by protein mixing. Furthermore, BALB/c mice vaccinated with a mixture of Anthrax vaccine adsorbed (AVA) and quaternary chitosan-coated liposomes showed faster and stronger anti-PA IgG inductions compared to those vaccinated with AVA alone, with titers positively correlating with the amount of cationic liposome used. This finding clearly reveals that quaternary chitosan-coated liposomes act as both nano-carriers and vaccine adjuvants that significantly enhance in-vivo immune responses to vaccines with low immunogenicities.


Assuntos
Endocitose , Lipossomos , Camundongos Endogâmicos BALB C , Lipossomos/química , Animais , Endocitose/efeitos dos fármacos , Camundongos , Polieletrólitos/química , Quitosana/química , Microfluídica/métodos , Feminino
16.
Eur Urol Oncol ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38693018

RESUMO

BACKGROUND AND OBJECTIVE: Cryoablation is a traditional antitumor therapy with good prospects for development. The efficacy of endoscopic management as a kidney-sparing surgery for high-risk upper tract urothelial carcinoma (UTUC) remains controversial. Our aim was to evaluate the impact of endoscopic cryoablation (ECA) versus radical nephroureterectomy (RNU) on survival outcomes, renal function, and complications. METHODS: We retrospectively analyzed data for 116 patients with newly diagnosed high-risk UTUC who underwent either ECA (n = 13) or RNU (n = 103) from March 25, 2019 to December 8, 2021. Propensity score matching (1:4) using the nearest neighbor method was performed before analysis. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), intravesical recurrence-free survival (RFS), the change in renal function, and treatment-emergent adverse events (TEAEs). KEY FINDINGS AND LIMITATIONS: At median follow-up of 28.2 mo for the ECA group and 27.6 mo for the RNU group, 2-yr OS (82% vs 84%), PFS (73% vs 71%), and intravesical RFS (81% vs 83%) rates after matching did not significantly differ. A decline in renal function was observed after RNU, but not after ECA. Five (41.7%) patients in the ECA group reported six TEAEs, and 17 patients (35.4%) in the RNU group reported 20 TEAEs. CONCLUSIONS AND CLINICAL IMPLICATIONS: In comparison to RNU, ECA for UTUC resulted in noninferior oncological outcomes and superior preservation of renal function. PATIENT SUMMARY: Our study suggests that a treatment called endoscopic cryoablation for high-risk cancer in the upper urinary tract can help in preserving kidney function, with similar survival outcomes to those after more extensive surgery. This option can be considered for selected patients with a strong preference for kidney preservation.

17.
Acta Pharm Sin B ; 14(9): 3916-3930, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39309483

RESUMO

Tumor relapse and metastasis are the major causes of mortality associated with urothelial cancer. In the tumor microenvironment, negative regulatory molecules and various immune cell subtypes suppress antitumor immunity. The inflammatory microenvironment, associated with neutrophils and neutrophil extracellular traps (NETs), promotes tumor metastasis. However, no drugs are currently available to specifically inhibit neutrophils and NETs. In this study, we first demonstrated that icaritin (ICT), a Chinese herbal remedy that is a first-line treatment for advanced and incurable hepatocellular carcinoma, reduces NETs caused by suicidal NETosis and prevents neutrophil infiltration in the tumor microenvironment. Mechanistically, ICT binds to and inhibits the expression of PADI2 in neutrophils, thereby suppressing PADI2-mediated histone citrullination. Moreover, ICT inhibits ROS generation, suppresses the MAPK signaling pathway, and inhibits NET-induced tumor metastasis. Simultaneously, ICT inhibits tumoral PADI2-mediated histone citrullination, which consequently suppresses the transcription of neutrophil-recruiting genes such as GM-CSF and IL-6. The downregulation of IL-6 expression, in turn, forms a regulatory feedback loop through the JAK2/STAT3/IL-6 axis. Through a retrospective study of clinical samples, we found a correlation between neutrophils, NETs, UCa prognosis, and immune evasion. Combining ICT with immune checkpoint inhibitors may have synergistic effects. In summary, our study demonstrated that ICT could be a novel inhibitor of NETs and a novel UCa treatment.

18.
J Cancer Res Clin Oncol ; 149(7): 3023-3031, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35852618

RESUMO

PURPOSE: Recent studies have demonstrated that kinetochore-associated protein 1 (KNTC1) plays a significant role in the carcinogenesis of numerous types of cancer. This study aimed to explore the role and possible mechanisms of KNTC1 in the development of pancreatic cancer. METHODS AND RESULTS: We analyzed differentially expressed genes by RNA sequencing in three paired pancreatic cancer and para-cancerous tissue samples and found that the expression of KNTC1 was significantly upregulated in pancreatic cancer. A Cancer and Tumor Gene Map pan-analysis showed that high expression of KNTC1 was related to poor prognosis in 9499 tumor samples. With immunohistochemical staining, we found that the high expression of KNTC1 in pancreatic cancer was related to pathological grade and clinical prognosis. Similarly, RT-PCR results indicated that the expression of KNTC1 was higher in three groups of pancreatic cancer cell lines (BxPC-3, PANC-1, and SW1990) than in normal pancreatic ductal cells. We introduced lentivirus-mediated shRNA targeting KNTC1 into PANC-1 and SW1990 cells and found that KNTC1 knockdown significantly decreased cell growth and increased cell apoptosis compared to the control group cells. Bioinformatic analysis of the cell expression profile revealed that differential genes were mainly enriched in the cell cycle, mitosis, and STAT3 signaling pathways, and co-immunoprecipitation confirmed an interaction between KNTC1 and cell division cycle associated 8. CONCLUSIONS: KNTC1 could be linked to the pathophysiology of pancreatic cancer and may be an early diagnostic marker of cervical precancerous lesions.


Assuntos
Apoptose , Neoplasias Pancreáticas , Humanos , Apoptose/genética , Linhagem Celular Tumoral , Neoplasias Pancreáticas/patologia , Proliferação de Células/genética , Oncogenes , Regulação Neoplásica da Expressão Gênica , Proteínas Associadas aos Microtúbulos/genética , Proteínas de Ciclo Celular/genética , Neoplasias Pancreáticas
19.
J Sci Comput ; 97(2)2023.
Artigo em Inglês | MEDLINE | ID: mdl-38938875

RESUMO

The regularized optimal mass transport (rOMT) problem adds a diffusion term to the continuity equation in the original dynamic formulation of the optimal mass transport (OMT) problem proposed by Benamou and Brenier. We show that the rOMT model serves as a powerful tool in computational fluid dynamics for visualizing fluid flows in the glymphatic system. In the present work, we describe how to modify the previous numerical method for efficient implementation, resulting in a significant reduction in computational runtime. Numerical results applied to synthetic and real-data are provided.

20.
RSC Adv ; 13(45): 31602-31615, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37908665

RESUMO

There is a need for non-pharmaceutical intervention methods that can prevent and indicate the risk of airborne disease spread. In this study, we developed a nonwoven mat based on the polyphenol gallic acid, which can inhibit pathogens growth and also indicate pathogen levels in the surrounding environment. Using nuclear magnetic resonance, Fourier-transform infrared spectroscopy, and high-performance liquid chromatography, we characterized this novel gelatin-based nonwoven mat and investigated the mechanism governing its ability to indicate pathogen levels. We demonstrated that the incorporation of gallic acid serves a vital role in indicating the presence of bacteria, causing the nonwoven mat to change in color from white to brown. We have proposed a plausible mechanism for this color change behavior based on a reaction of gallic acid with components excreted by bacteria, including glutamate, valine, and leucine. The concentrations of these components reflect the bacterial counts, enabling a real-time indication of pathogen levels in the surrounding air. In summary, the nonwoven mat presented herein can serve as an excellent antibacterial agent and as an indicator of nearby bacteria for fabricating personal protection equipment like filtration mask.

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