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1.
Brief Bioinform ; 25(3)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38627939

RESUMO

The latest breakthroughs in spatially resolved transcriptomics technology offer comprehensive opportunities to delve into gene expression patterns within the tissue microenvironment. However, the precise identification of spatial domains within tissues remains challenging. In this study, we introduce AttentionVGAE (AVGN), which integrates slice images, spatial information and raw gene expression while calibrating low-quality gene expression. By combining the variational graph autoencoder with multi-head attention blocks (MHA blocks), AVGN captures spatial relationships in tissue gene expression, adaptively focusing on key features and alleviating the need for prior knowledge of cluster numbers, thereby achieving superior clustering performance. Particularly, AVGN attempts to balance the model's attention focus on local and global structures by utilizing MHA blocks, an aspect that current graph neural networks have not extensively addressed. Benchmark testing demonstrates its significant efficacy in elucidating tissue anatomy and interpreting tumor heterogeneity, indicating its potential in advancing spatial transcriptomics research and understanding complex biological phenomena.


Assuntos
Benchmarking , Perfilação da Expressão Gênica , Análise por Conglomerados , Redes Neurais de Computação
2.
Eur J Med Res ; 29(1): 151, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429762

RESUMO

BACKGROUND: Urosepsis is a life-threatening organ disease in which pathogenic microorganisms in the urine enter the blood through the vessels, causing an imbalance in the immune response to infection. The aim of this study was to elucidate the role of testicular orphan receptor 4 (TR4) in urosepsis. METHODS: The role of TR4 in the progression and prognosis of urosepsis was confirmed by analyzing data from online databases and clinical human samples. To mimic urosepsis, we injected E. coli bacteria into the renal pelvis of mice to create a urosepsis model. Hematoxylin and eosin staining was used to observe histopathological changes in urosepsis. The effects of the upregulation or downregulation of TR4 on macrophage pyroptosis were verified in vitro. Chromatin immunoprecipitation assay was used to verify the effect of TR4 on Gasdermin D (GSDMD) transcription. RESULTS: TR4 was more highly expressed in the nonsurviving group than in the surviving group. Furthermore, overexpressing TR4 promoted inflammatory cytokine expression, and knocking down TR4 attenuated inflammatory cytokine expression. Mechanistically, TR4 promoted pyroptosis by regulating the expression of GSDMD in urosepsis. Furthermore, we also found that TR4 knockdown protected mice from urosepsis induced by the E. coli. CONCLUSIONS: TR4 functions as a key regulator of urosepsis by mediating pyroptosis, which regulates GSDMD expression. Targeting TR4 may be a potential strategy for urosepsis treatment.


Assuntos
Líquidos Corporais , Sepse , Animais , Humanos , Camundongos , Citocinas , Amarelo de Eosina-(YS) , Escherichia coli , Gasderminas , Proteínas de Ligação a Fosfato/genética , Sepse/complicações , Sepse/genética
3.
Gland Surg ; 13(1): 45-58, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38323233

RESUMO

Background: Adipose-derived stem cells (ADSCs) are closely associated with the survival rate of transplanted fat in breast reconstruction after breast cancer surgery. Nevertheless, the intrinsic mechanisms regulating ADSCs adipogenic differentiation remain ambiguous. The aim of our study was to explore the relevant genes and pathways to elucidate the potential mechanisms of adipogenic differentiation in ADSCs. Methods: The Gene Expression Omnibus (GEO) dataset GSE61302 was downloaded and analyzed to identify differentially expressed genes (DEGs). Key genes and signaling pathways were obtained through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional and enrichment analysis. Protein-protein interaction (PPI) network and hub gene analyses were performed with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and Cytoscape software. Finally, the transcription levels of hub genes in the adipogenic differentiated group and undifferentiated group of ADSCs were compared via real-time quantitative polymerase chain reaction (RT-qPCR). Results: In total, 1,091 DEGs were identified through bioinformatics analysis of the adipogenic differentiated group and undifferentiated group. If was then found that the 10 downregulated key genes, CCNB1, NUSAP1, DLGAP5, TTK, CCNB2, KIF23, BUB1B, CDC20, CDCA8, and KIF11 may play important roles in the adipogenic differentiation of ADSCs. Subsequent in vitro experimental verification also revealed that the messenger RNA (mRNA) expression levels of cyclin B1 in adipogenic differentiated cells and undifferentiated cells were significantly different at the early stage (P<0.05), but there was no significant difference at the late stage (P>0.05). Conclusions: As a key gene, CCNB1 might be a potential biomarker in the adipogenic differentiation of ADSCs at the early stage.

4.
J Imaging Inform Med ; 37(3): 1160-1176, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38326533

RESUMO

In intraoperative brain cancer procedures, real-time diagnosis is essential for ensuring safe and effective care. The prevailing workflow, which relies on histological staining with hematoxylin and eosin (H&E) for tissue processing, is resource-intensive, time-consuming, and requires considerable labor. Recently, an innovative approach combining stimulated Raman histology (SRH) and deep convolutional neural networks (CNN) has emerged, creating a new avenue for real-time cancer diagnosis during surgery. While this approach exhibits potential, there exists an opportunity for refinement in the domain of feature extraction. In this study, we employ coherent Raman scattering imaging method and a self-supervised deep learning model (VQVAE2) to enhance the speed of SRH image acquisition and feature representation, thereby enhancing the capability of automated real-time bedside diagnosis. Specifically, we propose the VQSRS network, which integrates vector quantization with a proxy task based on patch annotation for analysis of brain tumor subtypes. Training on images collected from the SRS microscopy system, our VQSRS demonstrates a significant speed enhancement over traditional techniques (e.g., 20-30 min). Comparative studies in dimensionality reduction clustering confirm the diagnostic capacity of VQSRS rivals that of CNN. By learning a hierarchical structure of recognizable histological features, VQSRS classifies major tissue pathological categories in brain tumors. Additionally, an external semantic segmentation method is applied for identifying tumor-infiltrated regions in SRH images. Collectively, these findings indicate that this automated real-time prediction technique holds the potential to streamline intraoperative cancer diagnosis, providing assistance to pathologists in simplifying the process.


Assuntos
Neoplasias Encefálicas , Aprendizado Profundo , Análise Espectral Raman , Humanos , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/diagnóstico , Análise Espectral Raman/métodos , Redes Neurais de Computação , Aprendizado de Máquina Supervisionado
5.
BMC Cancer ; 23(1): 1114, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37968576

RESUMO

BACKGROUND: The establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is involved in the development of multiple malignancies. However, its role in hypopharyngeal carcinoma (HPC) progression remains uncharacterized. METHODS: This study employed bioinformatics to determine the ESCO2 expression in head and neck squamous cell carcinoma (HNSC) and normal tissues. In vitro cell proliferation, migration, apoptosis, and/or cell cycle distribution assays were used to determine the function of ESCO2 and its relationship with STAT1. Xenograft models were established in nude mice to determine ESCO2 in HPC growth in vivo. Co-immunoprecipitation/mass spectrometry (Co-IP/MS) was conducted to identify the potential ESCO2 binding partners. RESULTS: We found that ESCO2 expression was elevated in HNSC tissues, and ESCO2 depletion suppressed tumor cell migration in vitro and inhibited tumor growth in vitro and in vivo. Co-IP/MS and immunoblotting assays revealed the interaction between ESCO2 and STAT1 in HPC cells. STAT1-overexpression compromised ESCO2-mediated suppressive effects on HPC cell proliferation, viability, and migration. CONCLUSIONS: These findings suggest that ESCO2 is crucial in promoting HPC malignant progression through the STAT1 pathway and provides novel therapeutic targets for HPC treatment.


Assuntos
Segregação de Cromossomos , Neoplasias de Cabeça e Pescoço , Animais , Camundongos , Humanos , Camundongos Nus , Proliferação de Células , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Linhagem Celular Tumoral , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Acetiltransferases/genética , Proteínas Cromossômicas não Histona/genética
6.
Analyst ; 148(20): 5124-5132, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37681669

RESUMO

Targeted imaging is playing an increasingly important role in the early detection and precise diagnosis of cancer. This need has motivated research into sensory nanomaterials that can be constructed into imaging agents to serve as biosensors. Graphene quantum dots (GQDs) as a valuable nanoprobe show great potential for use in two-photon biological imaging. However, most as-prepared GQDs exhibit a low two-photon absorption cross-section, narrow spectral coverage, and "one-to-one" signal conversion mode, which greatly hamper their wide application in sensitive early-stage cancer detection. Herein, a versatile strategy has been employed to fabricate an aptamer Sgc8c-functionalized hybrid as a proof-of-concept of the signal amplification strategy for targeted cancer imaging. In this study, GQDs with two-photon imaging performance, and silica nanoparticles (SiO2 NPs) as nanocarriers to provide amplified recognition events by high loading of GQD signal tags, were adopted to construct a two-photon hybrid-based signal amplification strategy. Thus, the obtained hybrid (denoted SiO2@GQDs) enabled extremely strong fluorescence with a quantum yield up to 0.49, excellent photostability and biocompatibility, and enhanced bright two-photon fluorescence up to 2.7 times that of bare GQDs (excitation at 760 nm; emission at 512 nm). Moreover, further modification with aptamer Sgc8c showed little disruption to the structure of the SiO2@GQDs-hybrid and the corresponding two-photon emission. Hence, SiO2@GQDs-Sgc8c showed specific responses to target cells. Moreover, it could be used as a signal-amplifying two-photon nanoprobe for targeted cancer imaging with high specificity and great efficiency, which exhibits a distinct green fluorescence compared to that of GQDs-Sgc8c or SiO2@GQDs. This signal amplification strategy holds great potential for the accurate early diagnosis of tumors and offers new tools for the detection a wide variety of analytes in clinical application.


Assuntos
Grafite , Nanopartículas , Neoplasias , Pontos Quânticos , Humanos , Pontos Quânticos/química , Grafite/química , Dióxido de Silício/química , Nanopartículas/química , Oligonucleotídeos , Neoplasias/diagnóstico por imagem
7.
Vet Med Sci ; 9(1): 523-534, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36583994

RESUMO

BACKGROUND: Brucellosis, caused by Brucella spp., is a major zoonotic public health threat. Although several Brucella vaccines have been demonstrated for use in animals, Brucella spp. can cause human infection and to date, there are no human-use vaccines licensed by any agency. Recently, methods in vaccine informatics have made major breakthroughs in peptide-based epitopes, opening up a new avenue of vaccine development. OBJECTIVES: The purpose of this article was to identify potential antigenic peptides in Brucella by proteome and peptidome analyses. METHODS: Mouse infection models were first established by injection with Brucella and spleen protein profiles were then analysed. Subsequently, the major histocompatibility complex class I or II (major histocompatibility complex [MHC]-I/II)-binding peptides in blood samples were collected by immunoprecipitation and peptides derived from Brucella proteins were identified through liquid chromatography-mass spectrometry (LC-MS/MS). These peptides were then evaluated in a variety of ways, such as in terms of conservation in Brucella and synchronicity in predicted peptides (similarity and coverage), which allowed us to more effectively measure their antigenic potential. RESULTS: The expression of the inflammatory cytokines IL1B and IFN-γ was significantly altered in the spleen of infected mice and some Brucella proteins, such as Muri, AcpP and GroES, were also detected. Meanwhile, in blood, 35 peptides were identified and most showed high conservation, highlighting their potential as antigen epitopes for vaccine development. In particular, we identified four proteins containing both MHC-I- and MHC-II-binding peptides including AtpA, AtpD, DnaK and BAbS19_II02030. They were also compared with the predicted peptides to estimate their reliability. CONCLUSIONS: The peptides we screened could bind to MHC molecules. After being stimulated with antigen T epitopes, Memory T cells can stimulate T cell activation and promote immune responses. Our results indicated that the peptides we identified may be good candidate targets for the design of subunit vaccines and these results pave the way for the study of safer vaccines against Brucella.


Assuntos
Brucella , Animais , Camundongos , Proteoma , Cromatografia Líquida/veterinária , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/veterinária , Epitopos , Peptídeos
8.
Neural Regen Res ; 17(3): 594-600, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34380899

RESUMO

Previous studies have shown that vagus nerve stimulation can improve patients' locomotor function. The stimulation of the auricular vagus nerve, which is the only superficial branch of the vagus nerve, may have similar effects to vagus nerve stimulation. However, the precise mechanisms remain poorly understood. In this study, rat models of cerebral ischemia/reperfusion injury were established by modified Longa ligation. Twenty-four hours later, 7-day auricular vagus nerve stimulation was performed. The results showed that auricular vagus nerve stimulation promoted the secretion of acetylcholine, inhibited the secretion of interleukin-1ß, interleukin-6, and tumor necrosis factor-α, and reduced connexin 43 phosphorylation in the ischemic penumbra and motor cortex, promoting locomotor function recovery in rats with cerebral ischemia/reperfusion injury. These findings suggested that auricular vagus nerve stimulation promotes the recovery of locomotor function in rats with cerebral ischemia/reperfusion injury by altering the secretion of acetylcholine and inflammatory factors and the phosphorylation of connexin 43. This study was approved by the Animal Use and Management Committee of Shanghai University of Traditional Chinese Medicine on November 8, 2019 (approval No. PZSHUTCM191108014).

10.
Transl Androl Urol ; 10(4): 1821-1826, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33968671

RESUMO

Upper tract urothelial carcinoma (UTUC) is a rare malignant disease, and while locally advanced non-metastatic UTUC can be cured by radical nephroureterectomy (RNU), this procedure leaves patients at high risk of relapse and death from cancer. Though the FDA has currently approved five agents for the systemic immunotherapy treatment of urothelial carcinoma (UC) patients, the effect of immunotherapy in patients with recurrent UTUC still lacks specific evidence. Camrelizumab is a programmed cell death protein 1 (PD-1) inhibitor which has been approved for the treatment of recurrent or refractory classical Hodgkin lymphoma in China and have achieved improvement in a verity of solid tumors with manageable safety profile. We herein report a case of an 80-year-old woman diagnosed with localized UTUC (pT4N0M0) for which she underwent RNU but relapsed after 2 months. As the toxic effects of chemotherapy were intolerable for the patient, she received the PD-1 inhibitor Camrelizumab as a salvage treatment to stop tumor growth. The tumor shrank and the patient achieved partial response (PR) after eight cycles but progressed after 14 cycles. Based on the current evidence, our case indicated that Camrelizumab is a promising agent in treating locally advanced and recurrent UTUC patients with poor performance status and imparted renal function.

11.
Ophthalmologica ; 244(4): 326-333, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33045702

RESUMO

BACKGROUND: Retinoblastoma (RB) is a common intraocular malignant tumor in infants and young children. However, reports on the morphological descriptions of RB tumor cells from native and foreign scholars are rare. OBJECTIVES: To investigate the myelogram characteristics of RB with extraocular tumor extension and the morphological characteristics of tumor cells in the bone marrow and cerebrospinal fluid. METHODS: For the period from May 2011 to February 2015, we analyzed clinical data on 18 patients in our hospital diagnosed as having metastatic RB in the extraocular and other distant regions associated with clear bone marrow metastasis. The morphology of tumor cells in the bone marrow and cerebrospinal fluid was retrospectively analyzed after staining with Wright-Giemsa stain. A summary of the cytological characteristics was also presented. RESULTS: RB tumor cells in the bone marrow and cerebrospinal fluid not only appeared as aggregated clumps, but were distributed in a scattered manner. The tumor cells may present different characteristic morphologies in different cases, with different tumor cell smears from the same tumor mass even showing different features. According to the degree of tumor metastasis, changes in myelogram were significantly different. CONCLUSION: The tumor cells of RB patients show unique morphological characteristics in the bone marrow and cerebrospinal fluid. Therefore, correct identification of the cells is of great value in the diagnosis, staging, and prognosis of RB.


Assuntos
Neoplasias da Retina , Retinoblastoma , Medula Óssea , Pré-Escolar , Humanos , Lactente , Prognóstico , Neoplasias da Retina/diagnóstico , Retinoblastoma/diagnóstico , Estudos Retrospectivos
12.
Gland Surg ; 9(5): 1495-1501, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33224824

RESUMO

BACKGROUND: Previous studies have shown that sentinel lymph node biopsy (SLNB) can be successfully performed using methylene blue (MB); however, this method still has some drawbacks. Indocyanine green (ICG) fluorescence imaging, as a selective method, has the potential for guiding SLNB. This study aimed to compare the clinical sensitivity and efficacy between ICG and MB in SLNB in breast cancer. METHODS: A prospective study of 70 patients with biopsy-proven invasive breast cancer was conducted. Under the guidance of ICG and MB, administered by injection, SLNs were examined and removed. The detection rates, total number of SLNs detected, mean number of SLNs detected, and number of positive SLNs were compared between ICG and MB. RESULTS: The SLN detection rate was 100% and 93% (65/70) for ICG and MB, respectively. More SLNs were detected in the ICG group (243) than in the MB group (169). The mean number of SLNs detected with ICG and MB was 3.5±1.73 and 2.4±1.49, respectively. Moreover, there was a statistically significant difference between the number of SLNs detected using the two methods (t=6.648, P<0.05). Additionally, SLN metastasis was detected in 18 patients using ICG and 14 patients using MB; these patients immediately underwent axillary lymph node dissection (ALND). No postoperative complications were reported. CONCLUSIONS: ICG demonstrated a higher detection rate and better accuracy, as well as a lower false negative rate, than MB in detecting SLNs in breast cancer. ICG has potential as an alternative tool that could be clinically applied to detect SLNs in breast cancer patients.

13.
Oncol Rep ; 44(5): 2080-2092, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33000261

RESUMO

Emerging studies have demonstrated that long non­coding RNAs (lncRNAs) play essential roles in tumorigenesis. However, the role and function of lncRNAs in hypopharyngeal squamous cell carcinoma (HSCC) have not been completely elucidated. The present study explored the function of a novel lncRNA, RP11­156L14.1, in HSCC. RP11­156L14.1 was revealed to be highly expressed in HSCC tissues and cell lines. Knockdown of RP11­156L14.1 inhibited proliferation, migration, and invasion in HSCC cells. Furthermore, RP11­156L14.1 regulated epithelial­mesenchymal transition (EMT) by controlling EMT­related protein expression. Mechanistically, RP11­156L14.1 exerted its function as a competing endogenous RNA (ceRNA) and directly interacted with miR­548ao­3p. The present study also demonstrated that miR­548ao­3p regulated signal sequence receptor subunit 1 (SSR1) expression by targeting SSR1 3'­UTR. Moreover, the xenograft HSCC tumor model revealed that knockdown of RP11­156L14.1 markedly suppressed HSCC tumor growth in vivo. In summary, these findings indicated that the lncRNA RP11­156L14.1 functions as an oncogene in HSCC by competing with miR­548ao­3p in regulating SSR1 expression. The RP11­156L14.1/miR­548ao­3p/SSR1 axis could be utilized as a potential novel biomarker and therapeutic target for HSCC.


Assuntos
Proteínas de Ligação ao Cálcio/genética , Neoplasias Hipofaríngeas/genética , Glicoproteínas de Membrana/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Receptores de Peptídeos/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Adulto , Idoso , Animais , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Hipofaríngeas/patologia , Neoplasias Hipofaríngeas/cirurgia , Hipofaringe/patologia , Hipofaringe/cirurgia , Laringectomia , Masculino , Camundongos , Pessoa de Meia-Idade , Prognóstico , RNA Longo não Codificante/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Ensaios Antitumorais Modelo de Xenoenxerto
14.
J Int Med Res ; 48(9): 300060520950930, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878523

RESUMO

OBJECTIVE: To compare the efficacy of two different treatment approaches for auricular pseudocyst. METHODS: This retrospective study reviewed data from patients with auricular pseudocyst that were treated with either anterior wall resection plus radiofrequency ablation compression (surgical group) or simple aspiration and compression suturing (control group). The following outcomes were compared between the two groups: therapeutic response (cure, good or none), duration of postoperative medication (antibiotics) use, duration of postoperative pain, duration of recovery of appearance and rate of complications (infection, auricular thickening, incision swelling and recurrence). RESULTS: A total of 386 patients were enrolled in the study: 218 in the surgical group and 168 in the control group. Duration of postoperative medication use, duration of postoperative pain, duration of recovery of appearance and rate of postoperative complications were significantly lower in the surgical group compared with the control group. The overall therapeutic response (cure and good response) was significantly greater in the surgical group than in the control group. CONCLUSION: Auricular pseudocyst can be effectively treated by both of these methods, but anterior wall resection plus radiofrequency ablation compression might be more effective.


Assuntos
Ablação por Cateter , Cistos , Otopatias , Neoplasias Hepáticas , Ablação por Radiofrequência , Cistos/cirurgia , Otopatias/cirurgia , Humanos , Recidiva Local de Neoplasia , Estudos Retrospectivos , Resultado do Tratamento
15.
BMC Med Genet ; 21(1): 120, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32487029

RESUMO

BACKGROUND: Familial benign chronic pemphigus, also known as Hailey-Hailey disease (HHD), is a clinically rare bullous Dermatosis. However the mechanism has not been clarified. The study aim to detect novel mutations in exons of ATP2C1 gene in HHD patients; to explore the possible mechnism of HHD pathogenesis by examining the expression profile of hSPCA1, miR-203, p63, Notch1 and HKII proteins in the skin lesions of HHD patients. METHODS: Genomic DNA was extracted from peripheral blood of HHD patients. All exons of ATP2C1 gene in HHD patients were amplified by PCR and the products were purified and sequenced. All related signaling proteins of interest were stained by using skin lesion tissues from HHD patients and miR-203 levels were also determined. RESULTS: One synonymous mutation c.G2598A (in exon 26), one nonsense mutation c.C635A and two missense mutations c.C1286A (p.A429D) and c. A1931G (p. D644G) were identified. The nonsense mutation changed codon UCG to stop codon UAG, causing a premature polypeptide chain of the functional region A. The two missense mutations were located in the region P (phosphorylation region) and the Mn binding site of hSPCA1. The level of hSPCA1 was significantly decreased in HHD patients compared to the normal human controls, accompanied by an increase of miR-203 level and a decrease of p63 and HKII levels. CONCLUSION: In our study, we found four mutations in HHD. Meanwhile we found increase of miR-203 level and a decrease of p63 and HKII levels. In addition, Notch1, which was negatively regulated p63, is downregulated. These factors may be involved in the signaling pathways of HHD pathogenesis. Our data showed that both p63 and miR-203 may have significant regulatory effects on Notch1 in the skin.


Assuntos
ATPases Transportadoras de Cálcio/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Mutação , Pênfigo Familiar Benigno/diagnóstico , Pênfigo Familiar Benigno/genética , Sequência de Aminoácidos , Biópsia , ATPases Transportadoras de Cálcio/química , Éxons , Feminino , Estudos de Associação Genética/métodos , Humanos , Imuno-Histoquímica , Masculino , MicroRNAs/genética , Linhagem , Análise de Sequência de DNA , Transdução de Sinais , Pele/patologia
16.
J Cell Physiol ; 235(3): 2809-2824, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31535382

RESUMO

Breast cancer has become the most common cancer in women, and nontriple negative breast cancer (non-TNBC) accounts for 80-90% of all invasive breast cancers. Early detection, diagnosis, and treatment are considered key to a successful cure. Conventionally, breast imaging and needle core biopsy are used for detection and monitoring. However, small variations in volume might be ignored in imaging, and traditional biopsies are spatially and temporally limited, leading to a significant delay in cancer detection and thus prompting renewed focus on early and accurate diagnosis. In this article, we investigated whether there is an accurate molecule in peripheral blood that can help diagnose breast cancer. Similar to microRNAs, tRNA-derived fragments (tRFs) have been reported to be involved in many pathological processes in breast cancer, but whether they can serve as candidate biomarkers for breast cancer remains unclear. Using high-throughput sequencing technology, we identified 4,021 differentially expressed tRFs in normal and breast cancer cell lines, and eight tRFs were selected to establish a signature as a predictive biomarker of non-TNBC. Furthermore, quantitative reverse-transcriptase polymerase chain reaction was performed to verify the expression of the signature and analyze the correlation between dysregulated tRFs and breast cancer. The results indicated that tDR-7816, tDR-5334, and tDR-4733 might be promising biomarkers. Through further bioinformatics analysis, we predicted that tDR-7816 influences the xenobiotic metabolic processes that support the oncogenesis of breast cancer. In summary, our results provide a rationale for using circulating tDR-7816 expression as a novel potential biomarker for the diagnosis of patients with early non-TNBC.


Assuntos
Detecção Precoce de Câncer/métodos , RNA de Transferência/sangue , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinogênese/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Células MCF-7 , Pessoa de Meia-Idade , RNA de Transferência/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
17.
J Cell Physiol ; 235(1): 380-393, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31232476

RESUMO

Atherosclerosis (AS), a chronic disorder of large arteries, is the underlying pathological process of heart disease and stroke. Former researchers have found that microRNAs (miRs) are involved in the several key processes of AS. Apolipoprotein E knockout (ApoE-/- ) mice fed a high-fat-diet (HFD) to establish AS model. The expression of miR-103 was characterized in the mice model. The effects of miR-103 on inflammation and endoplasmic reticulum stress (ERS) were analyzed when the expression of miR-103 was inhibited in ApoE -/- mice fed an HFD and human aortic endothelial cells (HAECs) exposed to oxidized low-density lipoprotein (ox-LDL). The relationship between miR-103 and phosphatase and tensin homolog (PTEN) was identified by luciferase activity detection and real-time quantitative polymerase chain reaction (RT-qPCR). Gain- and loss-function approaches were further applied for investigating the regulatory effects of miR-103 and PTEN on ERS. Role of MAPK signaling was then analyzed using PD98059 to block this pathway. miR-103 was highly expressed in the ApoEApoE -/- mice fed an HFD. Downregulation of miR-103 suppressed inflammation and ERS in endothelial cells isolated from ApoE -/- mice fed a HFD and ox-LDL-exposed HAECs. In addition, miR-103 can target PTEN and downregulate its expression. Overexpression of PTEN reversed the miR-103-induced activation of MAPK signaling. Moreover, PTEN upregulation or MAPK signaling inhibition ease miR-103-induced inflammation and ERS in vivo and in vitro. Thus, miR-103 depletion restrains the progression of AS through blocking PTEN-mediated MAPK signaling.


Assuntos
Aterosclerose/genética , Aterosclerose/patologia , Estresse do Retículo Endoplasmático/genética , MicroRNAs/genética , PTEN Fosfo-Hidrolase/metabolismo , Animais , Apolipoproteínas E/genética , Células Cultivadas , Modelos Animais de Doenças , Flavonoides/farmacologia , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Inflamação/genética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/antagonistas & inibidores
18.
J Cell Biochem ; 120(3): 3801-3812, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30506709

RESUMO

Benign chronic familial pemphigus or Hailey-Hailey disease (HHD, OMIM 169600) is a rare, autosomal dominant blistering skin disorder characterized by suprabasal cell separation (acantholysis) of the epidermis. To date, the proteomic changes in skin lesions from HHD patients has not been reported yet. In this study, a sample of skin lesions from HHD patients was collected for isobaric tags for relative and absolute quantitation to analyze proteome changes compared with unaffected individuals. The 134 differentially expressed proteins were assigned to at least one Gene Ontology term, and 123 annotated proteins with significant matches were assigned to 187 known metabolic or signaling pathways listed in the Kyoto Encyclopedia of Genes and Genomes. Most of the altered proteins in skin lesions of HHD patients were enriched in pathways involved in the PI3K-Akt signaling, focal adhesion, extracellular matrix (ECM)-receptor interaction, and protein digestion and absorption, such as collagen family members, microfibril-associated glycoprotein 4 and plakophilin. The changes of proteins related to cell adhesion, ECM-receptor interaction, and protein folding and glycosylation suggested that strategy targeted to alter cell junction and extracellular microenvironment might provide a potential treatment for HHD.


Assuntos
Matriz Extracelular/genética , Adesões Focais/genética , Pênfigo Familiar Benigno/genética , Proteoma/genética , Receptores de Superfície Celular/genética , Adulto , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Estudos de Casos e Controles , Colágeno/genética , Colágeno/metabolismo , Enciclopédias como Assunto , Epiderme/metabolismo , Epiderme/patologia , Matriz Extracelular/patologia , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Feminino , Adesões Focais/metabolismo , Adesões Focais/patologia , Ontologia Genética , Glicoproteínas/genética , Glicoproteínas/metabolismo , Humanos , Queratinócitos/metabolismo , Queratinócitos/patologia , Redes e Vias Metabólicas/genética , Anotação de Sequência Molecular , Pênfigo Familiar Benigno/metabolismo , Pênfigo Familiar Benigno/patologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Placofilinas/genética , Placofilinas/metabolismo , Mapeamento de Interação de Proteínas , Proteoma/metabolismo , Proteômica/métodos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Superfície Celular/metabolismo , Transdução de Sinais
19.
Int J Nanomedicine ; 12: 6963-6972, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29033564

RESUMO

Hemangioma is a common benign tumor affecting infants. In this study, we prepared sodium morrhuate immunoliposomes through encapsulation of sodium morrhuate with liposomes coupled with an anti-VEGFR2/KDR antibody and examined its effect on the biology of human hemangioma endothelial cells (HECs). It was found that compared to the liposomal sodium morrhuate group, treatment with sodium morrhuate immunoliposomes facilitated cell detachment and apoptotic death. Confocal microscopy analysis revealed that sodium morrhuate immunoliposomes had a higher binding activity to HECs than liposomal sodium morrhuate. Apoptosis analysis further demonstrated that treatment with liposomal sodium morrhuate or sodium morrhuate immunoliposomes significantly induced apoptosis in HECs, compared to the control group. Western blot analysis revealed an induction of caspase-3 and caspase-9 levels and reduction of caspase-8 and Bcl-2 levels in HECs treated with liposomal sodium morrhuate or sodium morrhuate immunoliposomes. Taken together, these results indicate that sodium morrhuate immunoliposomes have an increased capacity to target HECs and promote mitochondrial apoptosis. Therefore, sodium morrhuate immunoliposomes may represent a promising agent in the treatment of hemangiomas.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Células Endoteliais/patologia , Hemangioma/tratamento farmacológico , Morruato de Sódio/administração & dosagem , Morruato de Sódio/uso terapêutico , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/imunologia , Bioensaio , Morte Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/ultraestrutura , Humanos , Lipossomos/administração & dosagem , Morruato de Sódio/farmacologia
20.
Patient Prefer Adherence ; 11: 1723-1727, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29042756

RESUMO

BACKGROUND: The purpose of this study is to examine the effect of psychological intervention on the life quality of patients with laryngeal cancer. METHODS: Two hundred and ten patients with laryngeal cancer were randomly assigned to the study group receiving psychological intervention and control group receiving routine nursing care. The Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and the Europe Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) were used to evaluate life quality. RESULTS: There were no significant differences in the scores of HAMD, HAMA, and EORTC QLQ-C30 between the 2 groups before treatment (P>0.05). After treatment, the scores in the study group were significantly different to those in the control group (P<0.05). In addition, the satisfaction rate and compliance rate of patients in the study group were increased, compared to the control group (P<0.05). CONCLUSION: Psychological intervention is beneficial in improving life quality in patients with laryngeal cancer after surgery.

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