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1.
Front Neurol ; 15: 1387260, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711554

RESUMO

Background: Autoimmune diseases have always been one of the difficult diseases of clinical concern. Because of the diversity and complexity of its causative factors, unclear occurrence and development process and difficult treatment, it has become a key disease for researchers to study. And the disease explored in this paper, anti-NMDA encephalitis, belongs to a common type of autoimmune encephalitis. However, the quality of articles and research hotspots in this field are not yet known. Therefore, in this field, we completed a bibliometric and visualization analysis from 2005 to 2023 in order to understand the research hotspots and directions of development in this field. Materials and methods: We searched the SCI-expanded databases using Web of Science's core databases on January 22, 2024 and used tools such as VOS viewer, Cite Space, and R software to visualize and analyze the authors, countries, journals, institutions, and keywords of the articles. Results: A total of 1,161 literatures were retrieved and analyzed in this study. China was the country with the most total publications, and USA and Spain were the most influential countries in the field of anti-NMDA encephalitis. University of Pennsylvania from USA was the institution with the highest number of publications. While Dalmau Josep is the most prolific, influential and contributing author who published one of the most cited articles in Lancet Neurology, which laid the foundation for anti-NMDA encephalitis research, the top three appearances of keyword analysis were: "antibodies", "diagnosis", and "autoimmune encephalitis." Conclusion: Bibliometric analysis shows that the number of studies on anti-NMDA encephalitis is generally increasing year by year, and it is a hot disease pursued by researchers. USA and Spain are leading in the field of anti-NMDA encephalitis, while China should continue to improve the quality of its own research. The suspected causes of anti-NMDA encephalitis other than ovarian teratoma and herpes simplex, the specific clinical manifestations that are not masked by psychiatric symptoms, the diagnostic modalities that are faster and more accurate than antibody tests, and the improvement of treatment modalities by evaluating prognosis of various types of patients are the hotspots for future research.

2.
Breast Cancer Res ; 26(1): 60, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594783

RESUMO

BACKGROUND: Small nucleolar RNAs (snoRNAs) play key roles in ribosome biosynthesis. However, the mechanism by which snoRNAs regulate cancer stemness remains to be fully elucidated. METHODS: SNORA68 expression was evaluated in breast cancer tissues by in situ hybridization and qRT‒PCR. Proliferation, migration, apoptosis and stemness analyses were used to determine the role of SNORA68 in carcinogenesis and stemness maintenance. Mechanistically, RNA pull-down, RNA immunoprecipitation (RIP), cell fractionation and coimmunoprecipitation assays were conducted. RESULTS: SNORA68 exhibited high expression in triple-negative breast cancer (TNBC) and was significantly correlated with tumor size (P = 0.048), ki-67 level (P = 0.037), and TNM stage (P = 0.015). The plasma SNORA68 concentration was significantly lower in patients who achieved clinical benefit. The SNORA68-high patients had significantly shorter disease-free survival (DFS) (P = 0.036). Functionally, SNORA68 was found to promote the cell stemness and carcinogenesis of TNBC in vitro and in vivo. Furthermore, elevated SNORA68 expression led to increased nucleolar RPL23 expression and retained RPL23 in the nucleolus by binding U2AF2. RPL23 in the nucleolus subsequently upregulated c-Myc expression. This pathway was validated using a xenograft model. CONCLUSION: U2AF2-SNORA68 promotes TNBC stemness by retaining RPL23 in the nucleolus and increasing c-Myc expression, which provides new insight into the regulatory mechanism of stemness.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Linhagem Celular Tumoral , RNA , Núcleo Celular , Regulação Neoplásica da Expressão Gênica , Carcinogênese/genética , Proliferação de Células/genética , Fator de Processamento U2AF/genética
3.
Am J Pathol ; 194(5): 656-672, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38325552

RESUMO

Idiopathic pulmonary fibrosis is a progressive interstitial lung disease for which there is no curative therapy available. Repetitive alveolar epithelial injury repair, myofibroblast accumulation, and excessive collagen deposition are key pathologic features of idiopathic pulmonary fibrosis, eventually leading to cellular hypoxia and respiratory failure. The precise mechanism driving this complex maladaptive process remains inadequately understood. WD repeat and suppressor of cytokine signaling box containing 1 (WSB1) is an E3 ubiquitin ligase, the expression of which is associated strongly with hypoxia, and forms a positive feedback loop with hypoxia-inducible factor 1α (HIF-1α) under anoxic condition. This study explored the expression, cellular distribution, and function of WSB1 in bleomycin (BLM)-induced mouse lung injury and fibrosis. WSB1 expression was highly induced by BLM injury and correlated with the progression of lung fibrosis. Significantly, conditional deletion of Wsb1 in adult mice ameliorated BLM-induced pulmonary fibrosis. Phenotypically, Wsb1-deficient mice showed reduced lipofibroblast to myofibroblast transition, but enhanced alveolar type 2 proliferation and differentiation into alveolar type 1 after BLM injury. Proteomic analysis of mouse lung tissues identified caveolin 2 as a potential downstream target of WSB1, contributing to BLM-induced epithelial injury repair and fibrosis. These findings unravel a vital role for WSB1 induction in lung injury repair, thus highlighting it as a potential therapeutic target for pulmonary fibrosis.


Assuntos
Fibrose Pulmonar Idiopática , Lesão Pulmonar , Animais , Camundongos , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Miofibroblastos/metabolismo , Lesão Pulmonar/patologia , Proteômica , Pulmão/patologia , Fibrose , Hipóxia/patologia , Fibrose Pulmonar Idiopática/patologia , Bleomicina/toxicidade , Regeneração , Peptídeos e Proteínas de Sinalização Intracelular
4.
Mol Carcinog ; 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38421204

RESUMO

Breast cancer stem cells (BCSCs) are key players in carcinogenesis and development. Small nucleolar RNAs (snoRNAs) seem to have a crucial influence on regulating stem cell-like properties in various cancers, but the underlying mechanism in breast cancer has not been determined. In this study, we first found that the expression of SNORA51 might be strongly and positively related to BCSCs-like properties. SNORA51 expression was assessed in breast cancer tissues (n = 158 patients) by in situ hybridization. Colony formation, cell counting kit-8, and sphere formation assays were used to detect cell proliferation and self-renewal, respectively. Wound healing and transwell assays were used to detect cell migration. Coimmunoprecipitation and molecular docking were used to determine the underlying mechanism through which SNORA51 regulates BCSCs-like properties. High SNORA51 expression was associated with a worse prognosis, overall survival, and disease-free survival, in 158 breast cancer patients and was also closely related to lymph node status, ER status, the Ki-67 index, histological grade, and TNM stage. Further analysis proved that SNORA51 could enhance and maintain stem cell-like properties, including cell proliferation, self-renewal, and migration, in breast cancer. Moreover, high SNORA51 expression could reduce nucleolar RPL3 expression, induce changes in the expression of NPM1 in the nucleolus and nucleoplasm, and ultimately increase c-MYC expression. Taken together, our findings demonstrated that SNORA51 could enhance BCSCs-like properties via the RPL3/NPM1/c-MYC pathway both in vitro and in vivo. Therefore, SNORA51 might be a significant biomarker and potential therapeutic target and might even provide a new viewpoint on the regulatory mechanism of snoRNAs in breast cancer or other malignant tumors.

5.
Chem Commun (Camb) ; 60(14): 1912-1915, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38259117

RESUMO

We developed a multiplex single-molecule quantitative assay of intracellular telomerase that used target-triggered signal amplification to enhance sensitivity, substrate reaction to increase signal stability, and quantum dots to enhance signal-to-noise ratio, obtaining an LOD of 5 × 10-14 IU for intracellular telomerase and LOD of 3 cells for multiple cancer cells.


Assuntos
Técnicas Biossensoriais , Pontos Quânticos , Telomerase , Humanos , Telomerase/metabolismo , Células HeLa , Nanotecnologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-38044636

RESUMO

DNA nanomachines could initiate the cascade reaction in an autonomous mode under the drive of triggers, which achieve the signal amplification for the bioimaging of intracellular biomarkers. Compared with the "always-on" nanomachine that possibly produces false-positive signals, a controllable nanomachine with the on-site activation could be better for accurate tumor imaging and precise tumor therapy. Till now, the endogenous and exogenous triggers have been developed to design the controllable nanosensors. However, their combinations to develop feasible DNA nanomachines have been rarely studied. Herein, we constructed a near-infrared (NIR)-light-controlled DNA nanomachine that was first activated by the NIR light and then induced a target-triggered amplification process under the drive of an endogenous stimulus. Owing to adenosine-5'-triphosphate (ATP) having much higher concentration in cancer cells than that in healthy cells and the extracellular fluid, the obtained DNA nanomachine was selectively activated in cancer cells with inhibited interference signals from the surrounding healthy tissues. With obvious advantages including the exogenous NIR light initiation, the selective activation by the target microRNA, and the sensitive acceleration by the ATP-induced strand recycling reaction, the constructed nanomachine could be used to image the intracellular microRNA with increased sensitivity. Besides, after modifying the DNA sequence with the photosensitizer molecules, the obtained nanomachine could perform the selective photodynamic therapy on the tumor sections with the outstandingly decreased side effects. Thus, we hope the designed nanomachine could provide some important hints to design feasible nanomachines for accurate tumor diagnosis and precise tumor therapy.

7.
Food Chem ; 428: 136819, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37437357

RESUMO

The structure characteristics, functional properties, antioxidant and hypoglycemic activities of pectins extracted from feijoa peel with water (FP-W), acid (FP-A) and alkali (FP-B) were investigated. Results showed that the feijoa peel pectins (FPs) were mainly composed of galacturonic acid, arabinose, galactose and rhamnose. FP-W and FP-A had higher proportion of homogalacturonan domain, degree of esterification and molecular weight (for main component) than FP-B; FP-B owned the highest yield, protein and polyphenol contents. FP-W had a compact and smooth surface morphology unlike FP-A and FP-B. FP-W and FP-A had better thermal stability than FP-B. The rheological analysis suggested that the FPs exhibited pseudoplastic fluid behavior, and the elastic characteristics were dominant. Results showed that FP-W and FP-B had superior antioxidant and hypoglycemic activities than FP-A. According to correlation analysis, monosaccharide composition, sugar ratios and degree of acetylation were chief factors affecting the functional properties, antioxidant and hypoglycemic activities of the FPs.


Assuntos
Antioxidantes , Feijoa , Antioxidantes/farmacologia , Antioxidantes/química , Pectinas/química , Peso Molecular , Galactose/química
8.
J Colloid Interface Sci ; 648: 585-594, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37311361

RESUMO

Transition metal phosphides (TMPs) are one of the most promising alternatives to noble metal electrocatalysts, but so far their activity and stability still fall short of expectations. Here, we prepare nitrogen-doped nickel-cobalt phosphide (N-NiCoP) and molybdenum phosphide (MoP) heterostructures engineered on nickel foam (NF) with nanosheet structure by high-temperature annealing and low-temperature phosphorylation. Notably, heteroatomic N doping and heterostructures construction are achieved together through a simple co-pyrolysis method. The distinctive composition can synergistically promote the electron transfer, lower the reaction barriers, thus improving the catalytic performance. Therefore, the modified MoP@N-NiCoP requires low overpotentials of 43 mV and 232 mV to reach 10 mA cm-2 current density for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) accompanied by satisfactory stability in 1 M KOH. Density functional theory (DFT) calculations reveal the electron coupling and synergistic interfacial effects at the heterogeneous interface. This study provides a new strategy for heterogeneous electrocatalysts with elemental doping to promote hydrogen applications.

9.
BMC Cancer ; 23(1): 320, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37024824

RESUMO

BACKGROUND: Bladder cancer is the tenth most common cancer worldwide. For patients with T1 high-grade or T2 bladder cancer, radical cystectomy is recommended. However, radical cystectomy is associated with various complications and has a detrimental impact on the quality of life. Bladder-sparing therapy has been widely explored in patients with muscle-invasive bladder cancer, and whether a combination of transurethral resection of bladder tumour (TURBT) with chemotherapy and immunotherapy shows definite superiority over TURBT plus chemotherapy is still a matter of debate. The aim of this study is to investigate the efficacy and safety of TURBT combined with chemotherapy and immunotherapy in bladder-sparing therapy in patients with T1 high-grade or T2 bladder cancer who are unwilling or unsuitable to undergo radical cystectomy. METHODS: An open-label, multi-institutional, two-armed randomized controlled study will be performed with 86 patients with T1 high-grade or T2 bladder cancer meeting the eligibility criteria. Participants in the experimental group (n = 43) will receive TURBT combined with chemotherapy (GC: gemcitabine 1000 mg/m2 on the 1st day and the 8th day, cisplatin 70 mg/m2 on the 2nd day, repeated every 21 days) and immunotherapy (toripalimab 240 mg on the 5th day, repeated every 21 days), and those in the control group (n = 43) will receive TURBT plus chemotherapy (GC). The primary outcome is pathological response, and the secondary outcomes include progression-free survival, overall survival, toxicities, and quality of life. DISCUSSION: To the best of our knowledge, this is the first study to evaluate the efficacy and safety of TURBT combined with GC regimen and toripalimab in bladder-sparing therapy in patients with T1 high-grade or T2 bladder cancer. The expected benefit is that the combination of TURBT with chemotherapy and immunotherapy would be more effective than TURBT plus chemotherapy without compromising the quality of life and increasing the toxicity. TRIAL REGISTRATION: ChiCTR2200060546, chictr.org.cn, registered on June 14, 2022.


Assuntos
Neoplasias da Bexiga Urinária , Bexiga Urinária , Humanos , Bexiga Urinária/patologia , Qualidade de Vida , Ressecção Transuretral de Bexiga , Resultado do Tratamento , Estadiamento de Neoplasias , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Cistectomia/métodos , Imunoterapia/efeitos adversos , Invasividade Neoplásica/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Anal Chem ; 95(13): 5601-5609, 2023 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-36960746

RESUMO

The construction of a sensitive strategy for in situ visualizing and dynamic tracing intracellular microRNA is of great importance. Via the toehold-mediated strand displacement process, the catalytic hairpin assembly (CHA) could offer several hundreds-fold signal amplifications. However, the CHA may produce certain background interferences since microRNA may exist in normal cells. In this work, we constructed an endogenously and sequentially activated signal amplification strategy to provide the amplified dual-color fluorescence imaging of microRNA in living cancer cells, which was comprised of two successive reaction processes: the activation of the preprotective catalytic probe by the endogenous glutathione (GSH) and the subsequent catalytic hairpin assembly on the surface of the upconversion nanoprobe triggered by the specific microRNA. Since the concentration of GSH in cancer cells was much higher than that in normal cells and the extracellular environment, the activation of the designed nanoprobe could be controlled at the desirable site. With the merits of the endogenous initiation and selective activation, the designed nanoprobe could achieve the bioimaging of microRNA in living cancer cells with high precision and reliability. Furthermore, via the introduction of a photosensitizer molecule into the DNA strand, the designed nanoplatform could achieve the precise photodynamic therapy (PDT) for cancer cells and malignant tumors under the irradiation of the NIR laser. This work provided a new avenue to achieve the accurate imaging of intracellular microRNA and guided precise PDT, which would offer powerful hints to the early diagnosis and therapy of malignant tumors.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Neoplasias , Fotoquimioterapia , MicroRNAs/genética , Reprodutibilidade dos Testes , Fármacos Fotossensibilizantes/farmacologia , DNA , Técnicas Biossensoriais/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico
11.
J Am Heart Assoc ; 12(7): e028299, 2023 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-36942752

RESUMO

Background Aberrant expression of circular RNAs (circRNAs) contributes to the initiation and progression of pulmonary hypertension (PH). Hypoxia-inducible factor (HIF) is a well-known modulator of hypoxia-induced PH. The role and underlying mechanism of circRNAs in the regulation of HIF expression remains elusive. Methods and Results We profiled pulmonary artery transcriptomes using RNA sequencing and screened circRNAs associated with hypoxia treatment. The expression of a novel circRNA, circ_chr11_67292179-67294612 (circ-myh8), was increased by hypoxia in a time-dependent manner. We evaluated the effects of circ-myh8 overexpression by adeno-associated virus or inhibition by short hairpin RNA on proliferation and cell cycling in mice and pulmonary artery smooth muscle cells. Overexpression of circ-myh8 promotes PH under normoxia, and disruption of circ-myh8 by short hairpin RNA mitigates PH in chronic hypoxic mice. Biologically, circ-myh8 induces the proliferation and cell-cycle progression of pulmonary artery smooth muscle cells in vivo and in vitro. Mechanistically, RNA pull-down and RNA immunoprecipitation assays were used to examine the interaction of circRNAs with the binding protein KAT7 (lysine acetyltransferase 7). The acetylation level of lysine 5 of histone H4 in the transcriptional initiation region of HIF1α was determined by chromatin immunoprecipitation assay followed by reverse transcription-quantitative polymerase chain reaction. Circ-myh8 acts as a modular scaffold to recruit histone acetyltransferase KAT7 to the promoters of HIF1α, which elicits acetylation of lysine 5 of histone H4 in their promoters. Conclusions Our findings not only reveal the pivotal roles of circ-myh8 in governing histone modification in anti-PH treatment but also advocate triggering the circ-myh8/KAT7/HIF1α pathway to combat PH.


Assuntos
Histona Acetiltransferases , Hipertensão Pulmonar , Subunidade alfa do Fator 1 Induzível por Hipóxia , Cadeias Pesadas de Miosina , RNA Circular , Animais , Camundongos , Proliferação de Células , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismo , Histonas , Hipertensão Pulmonar/genética , Hipóxia/genética , Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Lisina , RNA Circular/genética , RNA Interferente Pequeno , Cadeias Pesadas de Miosina/genética
12.
Acta Biomater ; 157: 538-550, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36494007

RESUMO

Most photosensitizer molecules used for the photodynamic therapy (PDT) are chemically-synthesized organic photosensitizer dyes which show several limitations such as unsatisfactory cell uptake, weak selectivity and off-target phototoxicity. Recently, genetically-encoded photosensitizers have attracted increasing attentions which provide the targeted cell elimination with single-cell precision. However, their applications are mainly limited by the shallow tissue penetration depth of the excitation light and the low cell apoptosis ratio. Herein, we developed a feasible upconversion nanoparticle (UCNP)-based optogenetic nanosystem with three-in-one functional integration: bio-imaging, NIR-triggered PDT and cascade gene therapy. Firstly, the mitochondria-targeted genetically-encoded photosensitizer was constructed and transfected into cancer cells. Then, the functional upconversion nanoprobe was constructed with the mitochondria targetability and then the siRNA was loaded on the surface of UCNPs via the reactive oxygen species (ROSs) sensitive chemical bond. After the transfection and incubation, both of the upconversion nanoprobe and the genetically-encoded photosensitizer were accumulated in the mitochondria of cancer cells. Under the NIR irradiation, the emission of UCNPs could excite the expressed protein photosensitizer to generate ROSs which then stimulated the release of siRNAs in a controllable manner, achieving PDT and cascade gene therapy. Since the generation of ROSs and the release of siRNA occurred in the mitochondria in-situ, the mitochondria-mediated cell apoptosis signal pathway would be activated to induce cell apoptosis and subsequently inhibit tumor growth. To the best of our knowledge, this is the first report about NIR laser-activated, organelle-localized genetically-encoded photosensitizers developed for cascade therapy, which will widen the application of optogenetic tools in the tumor therapy. STATEMENT OF SIGNIFICANCE: The application of genetically-encoded photosensitizers in photodynamic therapy (PDT) is mainly limited by the shallow tissue penetration depth of the excitation light and unsatisfactory therapeutic performance. In this experiment, we developed an upconversion nanoparticles-based optogenetic nanosystem to enhance the PDT and cascade gene therapy for malignant tumors. The expressed genetically-encoded photosensitizers were accumulated in the mitochondria, which were activated in situ by the upconversion nanoprobe. Besides, the photogenerated reactive oxygen species (ROSs) stimulated the release of siRNAs in a controllable manner. To the best of our knowledge, this is the first report about NIR laser-activated, genetically-encoded photosensitizers developed for organelle-localized controllable cascade therapy. We hope this work can accelerate the application of genetically-encoded photosensitizers in the tumor therapy.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/química , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio/metabolismo , Optogenética , Nanopartículas/química , Neoplasias/tratamento farmacológico , Terapia Genética , RNA Interferente Pequeno/uso terapêutico , Linhagem Celular Tumoral
13.
ACS Sens ; 7(12): 3611-3633, 2022 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-36455009

RESUMO

Acoustic-based imaging techniques, including ultrasonography and photoacoustic imaging, are powerful noninvasive approaches for tumor imaging owing to sound transmission facilitation, deep tissue penetration, and high spatiotemporal resolution. Usually, imaging modes were classified into "always-on" mode and "activatable" mode. Conventional "always-on" acoustic-based probes often have difficulty distinguishing lesion regions of interest from surrounding healthy tissues due to poor target-to-background signal ratios. As compared, activatable probes have attracted attention with improved sensitivity, which can boost or amplify imaging signals only in response to specific biomolecular recognition or interactions. The tumor microenvironment (TME) exhibits abnormal physiological conditions that can be used to identify tumor sections from normal tissues. Various types of organic dyes and biomaterials can react with TME, leading to obvious changes in their optical properties. The TME also affects the self-assembly or aggregation state of nanoparticles, which can be used to design activatable imaging probes. Moreover, acoustic-based imaging probes and therapeutic agents can be coencapsulated into one nanocarrier to develop nanotheranostic probes, achieving tumor imaging and cooperative therapy. Satisfactorily, ultrasound waves not only accelerate the release of encapsulated therapeutic agents but also activate therapeutic agents to exert or enhance their therapeutic performance. Meanwhile, various photoacoustic probes can convert photon energy into heat under irradiation, achieving photoacoustic imaging and cooperative photothermal therapy. In this review, we focus on the recently developed TME-triggered ultrasound and photoacoustic theranostic probes for precise tumor imaging and targeted tumor therapy.


Assuntos
Neoplasias , Fototerapia , Humanos , Fototerapia/métodos , Medicina de Precisão , Microambiente Tumoral , Nanomedicina Teranóstica/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Acústica
14.
Anal Chem ; 94(50): 17670-17676, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36490323

RESUMO

Epigenetic DNA modifications, such as 5-methylcytosine, 5-hydroxymethylcytosine, and 5-formylcytosine, are associated with a variety of diseases and potential biomarkers for cancer diagnosis and therapy. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays are considered to be the gold standard for qualitative and quantitative detection of DNA modifications. DNA digestion for converting long DNA polymer into 2'-deoxynucleosides is an important preprocessing step to achieve sensitive and accurate LC-MS/MS quantification. Here, we showed that, as stimulated by divalent metal ions, Mg2+ and Mn2+, the engineered human DNase I Q9R:E13R:N74K mutant can efficiently digest DNA in the presence of monovalent metal ions at a high concentration (e.g., 1 M NaCl), showing hyperactivity on DNA cutting. We also found that the engineered DNase I mutants display exceptional DNA-cutting activity over a wider pH range (5.5-9.5). Due to their hyperactivity and high salt tolerance, the engineered DNase I mutants cut DNA 5mC and dC efficiently. Benefitting from this DNA-cutting hyperactivity, we demonstrated an LC-MS/MS assay for unbiased and accurate quantification of DNA 5mC.


Assuntos
Desoxirribonuclease I , Espectrometria de Massas em Tandem , Humanos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Cromatografia Líquida de Alta Pressão , DNA/química , Epigênese Genética
15.
Front Immunol ; 13: 807840, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35812443

RESUMO

Prostate cancer, recognized as a "cold" tumor, has an immunosuppressive microenvironment in which regulatory T cells (Tregs) usually play a major role. Therefore, identifying a prognostic signature of Tregs has promising benefits of improving survival of prostate cancer patients. However, the traditional methods of Treg quantification usually suffer from bias and variability. Transcriptional characteristics have recently been found to have a predictive power for the infiltration of Tregs. Thus, a novel machine learning-based computational framework has been presented using Tregs and 19 other immune cell types using 42 purified immune cell datasets from GEO to identify Treg-specific mRNAs, and a prognostic signature of Tregs (named "TILTregSig") consisting of five mRNAs (SOCS2, EGR1, RRM2, TPP1, and C11orf54) was developed and validated to monitor the prognosis of prostate cancer using the TCGA and ICGC datasets. The TILTregSig showed a stronger predictive power for tumor immunity compared with tumor mutation burden and glycolytic activity, which have been reported as immune predictors. Further analyses indicate that the TILTregSig might influence tumor immunity mainly by mediating tumor-infiltrating Tregs and could be a powerful predictor for Tregs in prostate cancer. Moreover, the TILTregSig showed a promising potential for predicting cancer immunotherapy (CIT) response in five CIT response datasets and therapeutic resistance in the GSCALite dataset in multiple cancers. Our TILTregSig derived from PBMCs makes it possible to achieve a straightforward, noninvasive, and inexpensive detection assay for prostate cancer compared with the current histopathological examination that requires invasive tissue puncture, which lays the foundation for the future development of a panel of different molecules in peripheral blood comprising a biomarker of prostate cancer.


Assuntos
Neoplasias da Próstata , Linfócitos T Reguladores , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Fatores Imunológicos/metabolismo , Imunoterapia/métodos , Masculino , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/terapia , Microambiente Tumoral
16.
Int Immunopharmacol ; 109: 108783, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35561479

RESUMO

The rapid development of bioengineering technology has introduced Fc-fusion proteins, representing a novel kind of recombinant protein, as promising biopharmaceutical products in tumor therapy. Numerous related anti-tumor Fc-fusion proteins have been investigated and are in different stages of development. Fc-fusion proteins are constructed by fusing the Fc-region of the antibody with functional proteins or peptides. They retain the bioactivity of the latter and partial properties of the former. This structural and functional advantage makes Fc-fusion proteins an effective tool in tumor immunotherapy, especially for the recruitment and activation of natural killer (NK) cells, which play a critical role in tumor immunotherapy. Even though tumor cells have developed mechanisms to circumvent the cytotoxic effect of NK cells or induce defective NK cells, Fc-fusion proteins have been proven to effectively activate NK cells to kill tumor cells in different ways, such as antibody-dependent cell-mediated cytotoxicity (ADCC), activate NK cells in different ways in order to promote killing of tumor cells. In this review, we focus on NK cell-based immunity for cancers and current research progress of the Fc-fusion proteins for anti-tumor therapy by activating NK cells.


Assuntos
Fragmentos Fc das Imunoglobulinas , Células Matadoras Naturais , Citotoxicidade Celular Dependente de Anticorpos , Fragmentos Fc das Imunoglobulinas/genética , Imunoterapia , Proteínas Recombinantes de Fusão/genética
17.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(3): 376-379, 2022 Mar 15.
Artigo em Chinês | MEDLINE | ID: mdl-35293181

RESUMO

Objective: To review the definition and possible etiologies for C 5 palsy. Methods: The literature on C 5 palsy at home and abroad in recent years was extensively reviewed, and the possible etiologies were analyzed based on clinical practice experience. Results: There are two main theories (nerve root tether and spinal cord injury) accounting for the occurrence of C 5 palsy, but both have certain limitations. The former can not explain the occurrence of C 5 palsy after anterior cervical spine surgery, and the latter can not explain that the clinical symptoms of C 5 palsy is often the motor dysfunction of the upper limb muscles. Based on the previous reports, combining our clinical experience and research, we propose that the occurrence of C 5 palsy is mainly due to the instrumental injury of anterior horn of cervical spinal cord during anterior cervical decompression. In addition, the C 5 palsy following surgery via posterior approach may be related to the nerve root tether caused by the spinal cord drift after decompression. Conclusion: In view of the main cause of C 5 palsy after cervical decompression, it is recommended to reduce the compression of the spinal cord by surgical instruments to reduce the risk of this complication.


Assuntos
Vértebras Cervicais , Descompressão Cirúrgica , Vértebras Cervicais/cirurgia , Humanos , Pescoço/cirurgia , Paralisia/epidemiologia , Paralisia/etiologia , Paralisia/cirurgia
18.
Carbohydr Polym ; 286: 119309, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35337516

RESUMO

Asteris Radix et Rhizoma (AR) has been widely used as a herbal medicine for treating various symptoms and possesses a number of bioactivities. A neutral polysaccharide ARP-1 was isolated from AR with weight-average molecular weight of 214 kDa. The heteropolysaccharide ARP-1 was composed of fucose, arabinose, galactose, glucose and mannose with a molar ratio of 0.40:14.25:10.22:1.06:0.41. Linkage and NMR analysis showed that ARP-1 had a backbone containing →3,6)-ß-d-Galp-(1→ and →6)-ß-d-Galp-(1 â†’ residues, and oligosaccharide side chains containing Araf and Galp units were attached to the backbone at C-3 of →3,6)-ß-d-Galp-(1 â†’ residues. Antioxidant activity assays showed that ARP-1 exhibited potent antioxidant activities, including ABTS, hydroxy and DPPH radicals scavenging and reducing power. Besides, ARP-1 decreased the production of ROS and MDA, and improved the activities of SOD, which resulted in the protection of PC12 cells against H2O2-induced oxidative stress. The findings indicated that ARP-1 might be used as a potential natural antioxidant.


Assuntos
Antioxidantes , Peróxido de Hidrogênio , Animais , Antioxidantes/química , Carboidratos da Dieta , Galactose/química , Polissacarídeos/química , Ratos
19.
Chem Commun (Camb) ; 58(10): 1617-1620, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35019909

RESUMO

A sequentially responsive nanocarrier was fabricated with three-in-one functional integration: bio-imaging, tumor microenvironment responsive chemotherapy and cascade activation of upconversion photodynamic therapy. The designed DNA outer nanoshell displayed site-specific degradation and controlled degradation speed. Significantly, the developed controllable nanotheranostic agent displayed high cell apoptosis ratios and obvious tumor inhibition.


Assuntos
Raios Infravermelhos , Nanoestruturas/química , Fotoquimioterapia/métodos , Animais , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/metabolismo , Antibióticos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/metabolismo , Doxorrubicina/farmacologia , Humanos , Nanopartículas Metálicas/química , Azul de Metileno/química , Azul de Metileno/farmacologia , Azul de Metileno/uso terapêutico , Camundongos , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Polímeros/química , Espécies Reativas de Oxigênio/metabolismo , Dióxido de Silício/química , Nanomedicina Teranóstica
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