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1.
Neoplasma ; 70(1): 145-157, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36916930

RESUMO

Growing evidence has indicated that circular RNAs (circRNAs) play crucial roles in the tumorigenesis and progression of diverse malignancies. However, the majority of circRNAs involved in esophageal squamous cell carcinoma (ESCC) remain undefined and the exact functions and underlying mechanisms of circRNAs in ESCC still need further exploration. In this study, we identified a novel onco-circRNA hsa_circ_0002938, derived from the exons of cysteine-rich transmembrane BMP regulator 1 (CRIM1) pre-mRNA, referred to as circCRIM1. We found that the expression of circCRIM1 was higher in ESCC tissues, compared to para-carcinoma tissues. Increased expression of circCRIM1 was positively correlated with clinical parameters of ESCC patients including tumor-node-metastasis (TNM) stage, tumor invasion range, and lymph node metastasis. Functionally, the results from the experiments in vitro showed that the knockdown of circCRIM1 suppressed proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in ESCC cells. By conducting bioinformatics algorithms analyses and microRNA (miRNA) rescue experiments, we found that circCRIM1 could act as a competing endogenous RNA (ceRNA) to sponge miR-342-3p in ESCC cells, and thereby upregulated the expression of transcription factor 12 (TCF12), a key regulator promoting the EMT process. Taken together, circCRIM1 facilitates the progression of ESCC by sponging miR-342-3p to regulate TCF12 and promote EMT, and the circCRIM1/miR-342-3p/TCF12 axis may be regarded as a potential predictive biomarker and therapeutic target for treating ESCC.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , MicroRNAs , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética
2.
Future Oncol ; 18(18): 2269-2288, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35440159

RESUMO

Aim: To explore the prognostic value of the systemic inflammatory response index (SIRI) and peripheral blood T-cell subsets in patients with hepatocellular carcinoma (HCC) and the relationship between them. Materials & methods: We treated 352 patients with HCC with sorafenib and/or immune checkpoint inhibitors (ICIs) and analyzed SIRI and peripheral blood T cells. Results: SIRI was an independent prognostic factor for patients with HCC receiving systemic therapy. Patients with high SIRI and low baseline peripheral blood T-cell counts showed a poor response to ICIs. SIRI was significantly and negatively correlated with CD3+, CD4+ and CD8+ T-cell counts. Conclusion: SIRI markers can be employed to noninvasively assess the presence of cancer-promoting inflammation in the tumor microenvironment and predict the efficacy of targeted therapy and immunotherapy.


Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. The change of immune microenvironment plays an important role in the occurrence and development of HCC. Recently, targeted therapy and immunotherapy have brought new hope to patients with advanced HCC. However, owing to the complexity of the immune microenvironment, not all patients can benefit from it. This study explores a simple, non-invasive method based on blood cell count to assess the immune microenvironment of HCC and predict the efficacy of treatment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas/patologia , Prognóstico , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Microambiente Tumoral
3.
J Nanobiotechnology ; 19(1): 138, 2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-33985511

RESUMO

BACKGROUND: Solid tumor hypoxic conditions prevent the generation of reactive oxygen species (ROS) and the formation of DNA double-strand breaks (DSBs) induced by ionizing radiation, which ultimately contributes to radiotherapy (RT) resistance. Recently, there have been significant technical advances in nanomedicine to reduce hypoxia by facilitating in situ O2 production, which in turn serves as a "radiosensitizer" to increase the sensitivity of tumor cells to ionizing radiation. However, off-target damage to the tumor-surrounding healthy tissue by high-energy radiation is often unavoidable, and tumor cells that are further away from the focal point of ionizing radiation may avoid damage. Therefore, there is an urgent need to develop an intelligent targeted nanoplatform to enable precise enhanced RT-induced DNA damage and combined therapy. RESULTS: Human epidermal growth factor receptor 2 (Her2)-specific dimeric affibody (ZHer2) mediated cisplatin-loaded mesoporous polydopamine/MnO2/polydopamine nanoparticles (Pt@mPDA/MnO2/PDA-ZHer2 NPs) for MRI and enhanced chemo-radiotherapy of Her2-positive ovarian tumors is reported. These NPs are biodegradable under a simulated tumor microenvironment, resulting in accelerated cisplatin release, as well as localized production of O2. ZHer2, produced using the E. coli expression system, endowed NPs with Her2-dependent binding ability in Her2-positive SKOV-3 cells. An in vivo MRI revealed obvious T1 contrast enhancement at the tumor site. Moreover, these NPs achieved efficient tumor homing and penetration via the efficient internalization and penetrability of ZHer2. These NPs exhibited excellent inhibition of tumor growth with X-ray irradiation. An immunofluorescence assay showed that these NPs significantly reduced the expression of HIF-1α and improved ROS levels, resulting in radiosensitization. CONCLUSIONS: The nanocarriers described in the present study integrated Her2 targeting, diagnosis and RT sensitization into a single platform, thus providing a novel approach for translational tumor theranostics.


Assuntos
Quimiorradioterapia/métodos , Cisplatino/química , Cisplatino/farmacologia , Nanopartículas/química , Polímeros/química , Receptor ErbB-2/química , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Escherichia coli/genética , Escherichia coli/metabolismo , Feminino , Humanos , Compostos de Manganês , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/uso terapêutico , Óxidos , Radiossensibilizantes , Espécies Reativas de Oxigênio/metabolismo , Receptor ErbB-2/genética , Hipóxia Tumoral , Microambiente Tumoral
4.
Sensors (Basel) ; 21(3)2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33530351

RESUMO

An easily fabricated Fabry-Perot optical fiber humidity sensor with high performance was presented by filling Graphene Quantum Dots (GQDs) into the Fabry-Perot resonator, which consists of two common single mode optical fibers. The relative humidity sensing performance was experimentally investigated by an interference spectrum drift between 11 %RH to 85 %RH. 0.567 nm/%RH sensitivity and 0.99917 linear correlation were found in experiments that showed high sensitivity, good and wide-range linear responding. Meanwhile, its good responding repeatability was demonstrated by two circle tests with increasing and decreasing relative humidity. For investigating the measurement influence caused by a temperature jitter, the temperature responding was experimentally investigated, which showed its linear responding with 0.033 nm/°C sensitivity. The results demonstrate the humidity sensitivity is greatly higher than the temperature sensitivity. The wavelength shift influence is 0.0198 nm with 0.6 °C max temperature jitter in the experiment, which can be ignored in humidity experiments. The fast-dynamic responses at typical humidity were demonstrated in experiments, with 5.5 s responding time and 8.5 s recovering time. The sensors with different cavity lengths were also investigated for their humidity response. All sensors gave good linear responding and high sensitivity. In addition, the relation curve between cavity length and response sensitivity also had good linearity. The combination of GQDs and single mode optical fibers showed easy fabrication and good performance for an optical fiber relative humidity sensor.

5.
Int J Colorectal Dis ; 35(7): 1255-1264, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32314191

RESUMO

OBJECTIVE: To explore whether the distance of rectal neuroendocrine neoplasms from the anal margin has an impact on the prognosis of patients and evaluate lymphatic metastases risk score for colorectal neuroendocrine neoplasms (NENs). METHODS: Clinical pathological and follow-up data of 71 patients identified as colorectal neuroendocrine neoplasms by pathology from July 2011 to July 2019 were carefully collected. RESULTS: Among 71 patients with colorectal NENs, most of the tumors were rectal NENs (62 cases). A total of 26 patients were in the presence of lymph node metastasis, and 44 patients had negative lymph nodes. Patients with lesions from the anal margin > 5 cm in rectum have a better prognosis (P = 0.022). Tumor stage (P = 0.034) and grade (P = 0.001) were independent risk predictors of lymphatic metastases. We developed a lymphatic metastasis risk score for rectal NENs, and patients with the score ≥ 7.5 were more likely to develop lymph node metastases (area 0.958, 95% CI 0.903-1.000, P = 0.000) with a sensitivity of 72.2% and a specificity of 97.3%. CONCLUSION: Patients with lesions from the anal margin > 5 cm and lymphatic metastasis risk score ≥ 7.5 should be treated actively.


Assuntos
Tumores Neuroendócrinos , Neoplasias Retais , Humanos , Metástase Linfática , Estadiamento de Neoplasias , Tumores Neuroendócrinos/patologia , Prognóstico , Neoplasias Retais/patologia , Estudos Retrospectivos , Fatores de Risco
6.
BMC Med Imaging ; 20(1): 110, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32972374

RESUMO

BACKGROUND: Coronary artery angiography is an indispensable assistive technique for cardiac interventional surgery. Segmentation and extraction of blood vessels from coronary angiographic images or videos are very essential prerequisites for physicians to locate, assess and diagnose the plaques and stenosis in blood vessels. METHODS: This article proposes a novel coronary artery segmentation framework that combines a three-dimensional (3D) convolutional input layer and a two-dimensional (2D) convolutional network. Instead of a single input image in the previous medical image segmentation applications, our framework accepts a sequence of coronary angiographic images as input, and outputs the clearest mask of segmentation result. The 3D input layer leverages the temporal information in the image sequence, and fuses the multiple images into more comprehensive 2D feature maps. The 2D convolutional network implements down-sampling encoders, up-sampling decoders, bottle-neck modules, and skip connections to accomplish the segmentation task. RESULTS: The spatial-temporal model of this article obtains good segmentation results despite the poor quality of coronary angiographic video sequences, and outperforms the state-of-the-art techniques. CONCLUSIONS: The results justify that making full use of the spatial and temporal information in the image sequences will promote the analysis and understanding of the images in videos.


Assuntos
Angiografia Coronária/métodos , Vasos Coronários/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Algoritmos , Vasos Coronários/cirurgia , Aprendizado Profundo , Humanos , Redes Neurais de Computação , Radiografia Intervencionista , Análise Espaço-Temporal , Gravação em Vídeo
7.
BMC Med Imaging ; 20(1): 65, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546137

RESUMO

BACKGROUND: Coronary heart disease is one of the diseases with the highest mortality rate. Due to the important position of cardiovascular disease prevention and diagnosis in the medical field, the segmentation of cardiovascular images has gradually become a research hotspot. How to segment accurate blood vessels from coronary angiography videos to assist doctors in making accurate analysis has become the goal of our research. METHOD: Based on the U-net architecture, we use a context-based convolutional network for capturing more information of the vessel in the video. The proposed method includes three modules: the sequence encoder module, the sequence decoder module, and the sequence filter module. The high-level information of the feature is extracted in the encoder module. Multi-kernel pooling layers suitable for the extraction of blood vessels are added before the decoder module. In the filter block, we add a simple temporal filter to reducing inter-frame flickers. RESULTS: The performance comparison with other method shows that our work can achieve 0.8739 in Sen, 0.9895 in Acc. From the performance of the results, the accuracy of our method is significantly improved. The performance benefit from the algorithm architecture and our enlarged dataset. CONCLUSION: Compared with previous methods that only focus on single image analysis, our method can obtain more coronary information through image sequences. In future work, we will extend the network to 3D networks.


Assuntos
Doenças Cardiovasculares/diagnóstico por imagem , Angiografia Coronária/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Algoritmos , Humanos , Redes Neurais de Computação
8.
Int Ophthalmol ; 40(12): 3529-3538, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32737725

RESUMO

PURPOSE: We aimed to evaluate the efficacy and safety of effective goniosynechialysis (GSL) under an endoscopic view combined with phacoemulsification in residual angle-closure glaucoma with lens opacity. METHODS: This was a retrospective study. Patients with residual angle-closure glaucoma, lens opacity, and uncontrolled intraocular pressure (IOP) who were receiving anti-glaucoma medications were selected to undergo effective GSL under an endoscopic view combined with phacoemulsification. Follow-up examinations were conducted until 6 months postoperatively. RESULTS: Twenty-five eyes of 24 patients diagnosed with residual angle-closure glaucoma and lens opacity and peripheral anterior synechiae (PAS) at least ≥ 270° were included. Their mean age was 61.32 ± 6.11 years. Preoperatively, the mean (standard error) IOP was 29.69 (11.22) mmHg, and the median number of IOP-lowering medications used was 3.0. The decreases in the rates of IOP of the patients were 44.29%, 52.17%, 46.95%, 48.37%, and 47.29% at 1 day, 1 week, 1 month, 2.5 months, and 6 months after the surgery, respectively. At 6 months, the median number of IOP-lowering medications used decreased from 3 to 0 and the range of PAS compared to the baseline decreased from 312° to 107° (P < 0.001). We also found that 21/25 eyes achieved improved or stable visual acuity after surgery. Postoperative complications included transiently elevated IOP (12.0%), exudation (8.0%), and hyphema (4.0%). CONCLUSIONS: Phacoemulsification combined with effective GSL under an endoscopic view may reopen residual angle-closure glaucoma and reduce the number of IOP-lowering medications for up to 6 months. It is an effective and safe method for patients with residual angle-closure glaucoma and lens opacity.


Assuntos
Extração de Catarata , Catarata , Glaucoma de Ângulo Fechado , Facoemulsificação , Idoso , Catarata/complicações , Glaucoma de Ângulo Fechado/complicações , Glaucoma de Ângulo Fechado/cirurgia , Humanos , Pressão Intraocular , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
9.
EMBO J ; 34(8): 987-1008, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25766254

RESUMO

Derived from any somatic cell type and possessing unlimited self-renewal and differentiation potential, induced pluripotent stem cells (iPSCs) are poised to revolutionize stem cell biology and regenerative medicine research, bringing unprecedented opportunities for treating debilitating human diseases. To overcome the limitations associated with safety, efficiency, and scalability of traditional iPSC derivation, expansion, and differentiation protocols, biomaterials have recently been considered. Beyond addressing these limitations, the integration of biomaterials with existing iPSC culture platforms could offer additional opportunities to better probe the biology and control the behavior of iPSCs or their progeny in vitro and in vivo. Herein, we discuss the impact of biomaterials on the iPSC field, from derivation to tissue regeneration and modeling. Although still exploratory, we envision the emerging combination of biomaterials and iPSCs will be critical in the successful application of iPSCs and their progeny for research and clinical translation.


Assuntos
Materiais Biocompatíveis/uso terapêutico , Células-Tronco Pluripotentes Induzidas/citologia , Regeneração , Reprogramação Celular , Regulação da Expressão Gênica , Terapia Genética/métodos , Humanos , Células-Tronco Pluripotentes Induzidas/transplante , Pesquisa com Células-Tronco , Transplante de Células-Tronco/métodos , Engenharia Tecidual/métodos
10.
BMC Biol ; 16(1): 62, 2018 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-29871632

RESUMO

BACKGROUND: Single-cell genomic methods now provide unprecedented resolution for characterizing the component cell types and states of tissues such as the epithelial subsets of the gastrointestinal tract. Nevertheless, functional studies of these subsets at scale require faithful in vitro models of identified in vivo biology. While intestinal organoids have been invaluable in providing mechanistic insights in vitro, the extent to which organoid-derived cell types recapitulate their in vivo counterparts remains formally untested, with no systematic approach for improving model fidelity. RESULTS: Here, we present a generally applicable framework that utilizes massively parallel single-cell RNA-seq to compare cell types and states found in vivo to those of in vitro models such as organoids. Furthermore, we leverage identified discrepancies to improve model fidelity. Using the Paneth cell (PC), which supports the stem cell niche and produces the largest diversity of antimicrobials in the small intestine, as an exemplar, we uncover fundamental gene expression differences in lineage-defining genes between in vivo PCs and those of the current in vitro organoid model. With this information, we nominate a molecular intervention to rationally improve the physiological fidelity of our in vitro PCs. We then perform transcriptomic, cytometric, morphologic and proteomic characterization, and demonstrate functional (antimicrobial activity, niche support) improvements in PC physiology. CONCLUSIONS: Our systematic approach provides a simple workflow for identifying the limitations of in vitro models and enhancing their physiological fidelity. Using adult stem cell-derived PCs within intestinal organoids as a model system, we successfully benchmark organoid representation, relative to that in vivo, of a specialized cell type and use this comparison to generate a functionally improved in vitro PC population. We predict that the generation of rationally improved cellular models will facilitate mechanistic exploration of specific disease-associated genes in their respective cell types.


Assuntos
Genômica/métodos , Organoides/citologia , Celulas de Paneth/citologia , Análise de Célula Única/métodos , Humanos , Modelos Biológicos , Proteômica , Análise de Sequência de RNA , Nicho de Células-Tronco
11.
Nat Methods ; 11(1): 106-12, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24292484

RESUMO

Although Lgr5(+) intestinal stem cells have been expanded in vitro as organoids, homogeneous culture of these cells has not been possible thus far. Here we show that two small molecules, CHIR99021 and valproic acid, synergistically maintain self-renewal of mouse Lgr5(+) intestinal stem cells, resulting in nearly homogeneous cultures. The colony-forming efficiency of cells from these cultures is ~100-fold greater than that of cells cultured in the absence of CHIR99021 and valproic acid, and multilineage differentiation ability is preserved. We made use of these homogeneous cultures to identify conditions employing simultaneous modulation of Wnt and Notch signaling to direct lineage differentiation into mature enterocytes, goblet cells and Paneth cells. Expansion in these culture conditions may be feasible for Lgr5(+) cells from the mouse stomach and colon and from the human small intestine. These methods provide new tools for the study and application of multiple intestinal epithelial cell types.


Assuntos
Técnicas de Cultura de Células/instrumentação , Técnicas de Cultura de Células/métodos , Colo/citologia , Intestino Delgado/citologia , Receptores Acoplados a Proteínas G/metabolismo , Células-Tronco/citologia , Animais , Diferenciação Celular , Células Cultivadas , Cromossomos/ultraestrutura , Citometria de Fluxo , Proteínas de Fluorescência Verde/metabolismo , Heterozigoto , Cariotipagem , Camundongos , Microscopia Confocal , Celulas de Paneth/citologia , Piridinas/química , Pirimidinas/química , Transdução de Sinais , Estômago/citologia , Ácido Valproico/química
12.
Neural Plast ; 2016: 8580675, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27867666

RESUMO

Protocadherin 15 (PCDH15) is a core component of hair cell tip-links and crucial for proper function of inner ear hair cells. Mutations of PCDH15 gene cause syndromic and nonsyndromic hearing loss. At present, the regulatory mechanisms responsible for the intracellular transportation of PCDH15 largely remain unknown. Here we show that PIST, a Golgi-associated, PDZ domain-containing protein, interacts with PCDH15. The interaction is mediated by the PDZ domain of PIST and the C-terminal PDZ domain-binding interface (PBI) of PCDH15. Through this interaction, PIST retains PCDH15 in the trans-Golgi network (TGN) and reduces the membrane expression of PCDH15. We have previously showed that PIST regulates the membrane expression of another tip-link component, cadherin 23 (CDH23). Taken together, our finding suggests that PIST regulates the intracellular trafficking and membrane targeting of the tip-link proteins CDH23 and PCDH15.


Assuntos
Caderinas/metabolismo , Proteínas de Transporte/fisiologia , Membrana Celular/metabolismo , Complexo de Golgi/metabolismo , Proteínas de Membrana/fisiologia , Precursores de Proteínas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Animais , Células COS , Proteínas Relacionadas a Caderinas , Caderinas/genética , Membrana Celular/genética , Galinhas , Chlorocebus aethiops , Complexo de Golgi/genética , Proteínas da Matriz do Complexo de Golgi , Células HEK293 , Humanos , Proteínas de Membrana Transportadoras , Camundongos , Ligação Proteica/fisiologia , Precursores de Proteínas/genética , Transporte Proteico/fisiologia
13.
J Biol Chem ; 289(35): 24215-25, 2014 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-24962568

RESUMO

The very large G protein-coupled receptor 1 (VLGR1) is a core component in inner ear hair cell development. Mutations in the vlgr1 gene cause Usher syndrome, the symptoms of which include congenital hearing loss and progressive retinitis pigmentosa. However, the mechanism of VLGR1-regulated intracellular signaling and its role in Usher syndrome remain elusive. Here, we show that VLGR1 is processed into two fragments after autocleavage at the G protein-coupled receptor proteolytic site. The cleaved VLGR1 ß-subunit constitutively inhibited adenylate cyclase (AC) activity through Gαi coupling. Co-expression of the Gαiq chimera with the VLGR1 ß-subunit changed its activity to the phospholipase C/nuclear factor of activated T cells signaling pathway, which demonstrates the Gαi protein coupling specificity of this subunit. An R6002A mutation in intracellular loop 2 of VLGR1 abolished Gαi coupling, but the pathogenic VLGR1 Y6236fsx1 mutant showed increased AC inhibition. Furthermore, overexpression of another Usher syndrome protein, PDZD7, decreased the AC inhibition of the VLGR1 ß-subunit but showed no effect on the VLGR1 Y6236fsx1 mutant. Taken together, we identified an independent Gαi signaling pathway of the VLGR1 ß-subunit and its regulatory mechanisms that may have a role in the development of Usher syndrome.


Assuntos
Proteínas de Transporte/fisiologia , Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo , Receptores Acoplados a Proteínas G/fisiologia , Animais , Sequência de Bases , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Primers do DNA , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , Proteólise , Receptores Acoplados a Proteínas G/metabolismo
14.
Cell Physiol Biochem ; 35(2): 616-26, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25612921

RESUMO

BACKGROUND: Nogo-A, a major myelin-associated inhibitor, can inhibit injured optic nerve regeneration. However, whether Amino-Nogo is the most important functional domain of Nogo-A remains unknown. This study aimed to identify the role of Amino-Nogo following optic nerve injury, and the mechanism of the Amino-Nogo-integrin αv signaling pathway in vivo. METHODS: Sprague-Dawley rats with optic nerve crush injury were injected with Nogo-A siRNA (Nogo-A-siRNA), the Nogo-66 functional domain antagonist peptide of Nogo-A (Nep1-40) or a recombinant rat Amino-Nogo-A protein (∆20) into the vitreous cavity to knock down Nogo-A, inhibit Nogo-66 or activate the Amino-Nogo, resparately. Retinal ganglion cell (RGC) density, axon regeneration and the pattern of NPN of visual electrophysiology (flash visual evoked potentials [F-VEP]) at different times post-injury were investigated. RESULTS: Our study revealed a lower RGC survival rate; shorter axonal outgrowth; longer N1, P1 and N2 waves latencies; and lower N1-P1 and P1-N2 amplitudes in the Δ20 group, and Δ20 treatment significantly attenuated integrin αv expression and phosphorylated focal adhesion kinase (p-FAK) levels. In the Nep1-40 and Nogo-A siRNA groups, there were higher RGC survival rates, longer axonal outgrowth, shorter N1 and P1 wave latencies, and higher N1-P1 and P1-N2amplitudes. Nogo-A siRNA treatment significantly increased integrin αv expression and p-FAK levels. Nepl-40 treatment did not alter integrin αv expression. In addition, there was no significant change in integrin α5 in any group. CONCLUSION: These results suggest that the integrin signaling pathway is regulated by Amino-Nogo, which inhibits optic nerve regeneration and functional recovery, and that the integrin subunit involved might be integrin αv but not integrin α5.


Assuntos
Integrina alfaV/metabolismo , Proteínas da Mielina/antagonistas & inibidores , Proteínas da Mielina/química , Regeneração Nervosa , Nervo Óptico/fisiopatologia , Transdução de Sinais , Animais , Potenciais Evocados Visuais , Técnicas de Silenciamento de Genes , Proteínas da Mielina/metabolismo , Proteínas Nogo , Nervo Óptico/citologia , Traumatismos do Nervo Óptico/metabolismo , Traumatismos do Nervo Óptico/fisiopatologia , Fragmentos de Peptídeos/metabolismo , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Células Ganglionares da Retina/metabolismo
16.
Stem Cells Dev ; 33(1-2): 11-26, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37897075

RESUMO

The homeostasis of the intestinal epithelium heavily relies on the self-renewal and differentiation of intestinal stem cells (ISCs). Although the orchestration of these processes by signaling pathways such as the Wnt, BMP, Notch, and MAPK signals has been extensively studied, the dynamics of their regulation remains unclear. Our study explores how the Wnt signaling pathway temporally regulates the differentiation of ISCs into various cell types in an intestinal organoid system. We report that the duration of Wnt exposure following Notch pathway inactivation significantly influences the differentiation direction of intestinal epithelial cells toward multiple secretory cell types, including goblet cells, enteroendocrine cells (EECs), and Paneth cells. This temporal regulation of Wnt signaling adds another layer of complexity to the combination of niche signals that govern cell fate. By manipulating this temporal signal, we have developed optimized protocols for the efficient in vitro differentiation of ISCs into EECs and goblet cells. These findings provide critical insights into the dynamic regulation of ISC differentiation and offer a robust platform for future investigations into intestinal biology and potential therapeutic applications.


Assuntos
Mucosa Intestinal , Intestinos , Diferenciação Celular/fisiologia , Mucosa Intestinal/metabolismo , Células-Tronco , Via de Sinalização Wnt/fisiologia , Organoides
17.
Heliyon ; 10(13): e33795, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39027504

RESUMO

Dysregulation of apoptosis occurs in different types of malignant tumors and is likely to influence the tumor evolution, as well as clinical prognosis. However, the limited number of studies investigating the predictive power of apoptosis-related genes (ARGs) in gastric cancer indicates a gap in the current research. 174 ARGs who differentially expressed were screened using public databases, including the Gene Expression Omnibus and the Molecular Signatures Database. Univariate and LASSO regression analyses were rigorous approaches to recognize the 12 optimal genes (CTHRC1, PDGFRL, VCAN, GJA1, LOX, UPP1, ANGPT2, CRIM1, HIF1A, APOD, RNase1, and ID1) that make up the prognostic risk model. Molecular mutations, related signaling pathways, and immune system characteristics in different subgroups defined by the risk model were analyzed using different R packages. Moreover, based on the database of Genomics of Drug Sensitivity in Cancer, chemotherapy sensitivity was predicted among the risk subgroups. As a result, there were differences in mutation profiles, signaling pathways, and infiltrated immune cells between patients in various risk groups. Moreover, the low-risk group displayed greater sensitivity to chemotherapy than the high-risk group. Risk model provided a better prognostic value than the T, N, and M stages, according to the receiver operating characteristic curve. Finally, in a nomogram, the risk model and clinical factors were combined to visualize the survival rates of patients with GC. In response to the differential expression of apoptosis-related genes, a novel model for predicting the prognosis of GC patients was developed. This model may be highly valuable for guiding doctors to deliver treatment plans tailored to the need of patients with GC.

18.
Int J Ophthalmol ; 17(7): 1370-1374, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39026920

RESUMO

Among refractive errors, astigmatism is the most common optical aberration, where refraction changes in different meridians of the eye. It causes blurred vision at any distance and includes corneal, lenticular, and retinal astigmatism. Cataract surgery used to cause a progressive increase in the pre-exisiting corneal astigmatism because of creating a surgically induced astigmatism, for example, a large size surgery incision. The development of surgical techniques during last decades has made cataract surgery interchange to treat preoperative corneal astigmatism at time of surgery. Nowadays, three surgical approaches can be used. By placing a sutureless clear corneal incision on the steep meridian of the cornea, a preoperative corneal astigmatism less than 1.0 D can be corrected. Single or paired peripheral corneal relaxing incisions (PCRIs) provide 1.0-3.0 D corneal astigmatism correction. PCRIs are typically used for treating 1.0-1.5 D of regular corneal astigmatism, if more than 2.0 D, the risk of overcorrection and irregular astigmatism is increased. When toric intraocular lenses (IOLs) are unavailable in markets, PCRIs are still a reasonable option for patients with up to 3.0 D of pre-existing corneal astigmatism. Toric IOLs implantation can correct 1.0-4.5 D of corneal astigmatism. Several IOLs are approved to correct a high degree of corneal astigmatism with cylinder power up to 12.0 D. These approaches can be used alone or in combination.

19.
ISME Commun ; 4(1): ycae022, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38500699

RESUMO

Northern peatlands contain ~30% of terrestrial carbon (C) stores, but in recent decades, 14% to 20% of the stored C has been lost because of conversion of the peatland to cropland. Microorganisms are widely acknowledged as primary decomposers, but the keystone taxa within the bacterial community regulating C loss from cultivated peatlands remain largely unknown. In this study, we investigated the bacterial taxa driving peat C mineralization during rice cultivation. Cultivation significantly decreased concentrations of soil organic C, dissolved organic C (DOC), carbohydrates, and phenolics but increased C mineralization rate (CMR). Consistent with the classic theory that phenolic inhibition creates a "latch" that reduces peat C decomposition, phenolics were highly negatively correlated with CMR in cultivated peatlands, indicating that elimination of inhibitory phenolics can accelerate soil C mineralization. Bacterial communities were significantly different following peatland cultivation, and co-occurrence diagnosis analysis revealed substantial changes in network clusters of closely connected nodes (modules) and bacterial keystone taxa. Specifically, in cultivated peatlands, bacterial modules were significantly negatively correlated with phenolics, carbohydrates, and DOC. While keystone taxa Xanthomonadales, Arthrobacter, and Bacteroidetes_vadinHA17 can regulate bacterial modules and promote carbon mineralization. Those observations indicated that changes in bacterial modules can promote phenolic decomposition and eliminate phenolic inhibition of labile C decomposition, thus accelerating soil organic C loss during rice cultivation. Overall, the study provides deeper insights into microbe-driven peat C loss during rice cultivation and highlights the crucial role of keystone bacterial taxa in the removal of phenolic constraints on peat C preservation.

20.
Sci Rep ; 14(1): 17719, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39085430

RESUMO

Swin Transformer is an important work among all the attempts to reduce the computational complexity of Transformers while maintaining its excellent performance in computer vision. Window-based patch self-attention can use the local connectivity of the image features, and the shifted window-based patch self-attention enables the communication of information between different patches in the entire image scope. Through in-depth research on the effects of different sizes of shifted windows on the patch information communication efficiency, this article proposes a Dual-Scale Transformer with double-sized shifted window attention method. The proposed method surpasses CNN-based methods such as U-Net, AttenU-Net, ResU-Net, CE-Net by a considerable margin (Approximately 3% ∼ 6% increase), and outperforms the Transformer based models single-scale Swin Transformer(SwinT)(Approximately 1% increase), on the datasets of the Kvasir-SEG, ISIC2017, MICCAI EndoVisSub-Instrument and CadVesSet. The experimental results verify that the proposed dual scale shifted window attention benefits the communication of patch information and can enhance the segmentation results to state of the art. We also implement an ablation study on the effect of the shifted window size on the information flow efficiency and verify that the dual-scale shifted window attention is the optimized network design. Our study highlights the significant impact of network structure design on visual performance, providing valuable insights for the design of networks based on Transformer architectures.

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