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The chicken embryo chorioallantoic membrane (CAM) model has played a crucial role in various aspects of cancer research. The purpose of this study is to help researchers clarify the research direction and prospects of the CAM model. A bibliometric analysis was conducted on the top 100 most cited articles on use of the CAM model in tumour research, retrieved from the Web of Science Core Collection database. Tools such as Bibliometrix, VOSviewer, CiteSpace and Excel were utilized for the visualization network analysis. The 100 articles analysed were mainly from the USA, China and European countries such as Germany and France. Tumour research involving CAM model experiments demonstrated reliability and scientific rigor (average citation count = 156.2). The analysis of keywords, topics and subject areas revealed that the applications of this model ranged from the biological characteristics of tumours to molecular mechanisms and signaling pathways, to recent developments in nanotechnology and clinical applications. Additionally, nude mouse experiments have been more frequently performed in recent years. We conclude that the CAM model is efficient, simple and cost-effective, and has irreplaceable value in various aspects of cancer research. In the future, the CAM model can further contribute to nanotechnology research.
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Nephroblastoma, an overexpressed gene (NOV) protein, plays an important role in proliferation, differentiation, angiogenesis, adhesion, invasion and tumorigenesis, but the function of amino-truncated NOV is different. This study is to investigate the role of amino-truncated NOV in the progression of bladder cancer. Using immunohistochemistry and Western blot analysis, we detected the amino-truncated NOV in bladder cancer, and statistical analysis was performed to estimate the association between the expression of amino-truncated NOV and the patient's prognosis by SPSS 19.0. With transduction of amino-truncated NOV, we evaluated alteration for proliferation, migration, invasion and chemoresistance in bladder cancer cells, as well as some proteins related to Wnt/ß-catenin pathway and epithelial-mesenchymal transition. The truncated variant of the NOV protein was located in a nucleus other than the cytoplasm and highly expressed in bladder cancer, which was also linked to higher pathological grade and positive lymph node metastasis as well as recurrence. The exact sequence of this truncated protein was confirmed, and it was a 26-kDa splicing. The truncated NOV protein found in bladder cancer was cut at the 187th amino acid of the full-length protein. It was also involved in bladder cancer progression and chemoresistance through a mechanism involving epithelial-mesenchymal transition (EMT) and the Wnt/ß-catenin signaling pathway. Our findings provide experimental evidence that the nuclear NOV protein expression is a potential biomarker in the prognostic evaluation of bladder cancer and enhanced amino-truncated NOV expression is potentially important for bladder cancer cell invasion, metastasis and chemoresistance during progression.
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Resistencia a Medicamentos Antineoplásicos , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/mortalidade , Prognóstico , Resistencia a Medicamentos Antineoplásicos/genética , Masculino , Feminino , Pessoa de Meia-Idade , Transição Epitelial-Mesenquimal/genética , Linhagem Celular Tumoral , Proliferação de Células , Idoso , Metástase Neoplásica , Via de Sinalização Wnt , Movimento Celular , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genéticaRESUMO
The vast neuronal diversity in the human neocortex is vital for high-order brain functions, necessitating elucidation of the regulatory mechanisms underlying such unparalleled diversity. However, recent studies have yet to comprehensively reveal the diversity of neurons and the molecular logic of neocortical origin in humans at single-cell resolution through profiling transcriptomic or epigenomic landscapes, owing to the application of unimodal data alone to depict exceedingly heterogeneous populations of neurons. In this study, we generated a comprehensive compendium of the developing human neocortex by simultaneously profiling gene expression and open chromatin from the same cell. We computationally reconstructed the differentiation trajectories of excitatory projection neurons of cortical origin and inferred the regulatory logic governing lineage bifurcation decisions for neuronal diversification. We demonstrated that neuronal diversity arises from progenitor cell lineage specificity and postmitotic differentiation at distinct stages. Our data paves the way for understanding the primarily coordinated regulatory logic for neuronal diversification in the neocortex.
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This report presents a case involving a woman aged >65 years who had been diagnosed with marginal zone lymphoma 3 years prior. The patient was hospitalized with enlarged inguinal lymph nodes, and pathological examination revealed that the lymphoma had transformed into diffuse large B-cell lymphoma. After two cycles of brentuximab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (BV-R-CHP) chemotherapy, the patient achieved complete remission. This treatment was followed by autologous hematopoietic stem cell transplantation and lenalidomide maintenance therapy. At the last follow-up, the patient had been in continuous remission for 24 months. This case study suggests that the utilization of BV and R-CHP in conjunction can result in rapid remission, and it can be followed by autologous hematopoietic stem cell transplantation and maintenance therapy with lenalidomide. This treatment approach exhibits potential as a viable option for older individuals with transformed lymphoma.
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Protocolos de Quimioterapia Combinada Antineoplásica , Brentuximab Vedotin , Doxorrubicina , Linfoma Difuso de Grandes Células B , Transplante Autólogo , Humanos , Feminino , Brentuximab Vedotin/uso terapêutico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Doxorrubicina/uso terapêutico , Doxorrubicina/administração & dosagem , Transplante de Células-Tronco de Sangue Periférico/métodos , Rituximab/uso terapêutico , Rituximab/administração & dosagem , Prednisona/uso terapêutico , Prednisona/administração & dosagem , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Lenalidomida/uso terapêutico , Lenalidomida/administração & dosagem , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Linfoma de Zona Marginal Tipo Células B/terapia , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma de Zona Marginal Tipo Células B/cirurgia , Terapia CombinadaRESUMO
Despite the advent of genomic sequencing, molecular diagnosis remains unsolved in approximately half of patients with Mendelian disorders, largely due to unclarified functions of noncoding regions and the difficulty in identifying complex structural variations. In this study, we map a unique form of central iris hypoplasia in a large family to 6q15-q23.3 and 18p11.31-q12.1 using a genome-wide linkage scan. Long-read sequencing reveals a balanced translocation t(6;18)(q22.31;p11.22) with intergenic breakpoints. By performing Hi-C on induced pluripotent stem cells from a patient, we identify two chromatin topologically associating domains spanning across the breakpoints. These alterations lead the ectopic chromatin interactions between APCDD1 on chromosome 18 and enhancers on chromosome 6, resulting in upregulation of APCDD1. Notably, APCDD1 is specifically localized in the iris of human eyes. Our findings demonstrate that noncoding structural variations can lead to Mendelian diseases by disrupting the 3D genome structure and resulting in altered gene expression.
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Cromatina , Iris , Linhagem , Translocação Genética , Humanos , Cromatina/metabolismo , Cromatina/genética , Iris/metabolismo , Masculino , Feminino , Cromossomos Humanos Par 6/genética , Cromossomos Humanos Par 18/genética , Células-Tronco Pluripotentes Induzidas/metabolismo , Adulto , Doenças da Íris/genética , Doenças da Íris/metabolismo , Doenças da Íris/patologia , Ligação GenéticaRESUMO
Indolin-3-ones are essential heterocycles with wide-ranging biological activities and medicinal values, and therefore, efficient approaches to their synthesis remain in demand. Herein, a novel and operationally simple method to generate indolin-3-ones is reported by using a tandem reaction of N-methylbenzylamines and methyl 2-fluorobenzoates mediated by the LiN(SiMe3)2 and CsF system (34 examples, 30-85% yields). The synthesis of C2-quaternary indolin-3-one further demonstrated the potential practicability of these tandem reactions.
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Although bacteriophage-based biosensors hold promise for detecting Staphylococcus aureus in food products in a timely, simple, and sensitive manner, the associated targeting mechanism of the biosensors remains unclear. Herein, a colourimetric biosensor SapYZU11@ZnFe2O4, based on a broad-spectrum S. aureus lytic phage SapYZU11 and a ZnFe2O4 nanozyme, was constructed, and its capacity to detect viable S. aureus in food was evaluated. Characterisation of SapYZU11@ZnFe2O4 revealed its effective immobilisation, outstanding biological activity, and peroxidase-like capability. The peroxidase activity of SapYZU11@ZnFe2O4 significantly decreased after the addition of S. aureus, potentially due to blockage of the nanozyme active sites. Moreover, SapYZU11@ZnFe2O4 can detect S. aureus from various sources and S. aureus isolates that phage SapYZU11 could not lyse. This may be facilitated by the adsorption of the special receptor-binding proteins on the phage tail fibre and wall teichoic acid receptors of S. aureus. Besides, SapYZU11@ZnFe2O4 exhibited remarkable sensitivity and specificity when employing colourimetric techniques to rapidly determine viable S. aureus counts in food samples, with a detection limit of 0.87 × 102 CFU/mL. Thus, SapYZU11@ZnFe2O4 has broad application prospects for the detection of viable S. aureus cells on food substrates.
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Técnicas Biossensoriais , Colorimetria , Contaminação de Alimentos , Microbiologia de Alimentos , Staphylococcus aureus , Staphylococcus aureus/isolamento & purificação , Técnicas Biossensoriais/métodos , Colorimetria/métodos , Contaminação de Alimentos/análise , Fagos de Staphylococcus , Limite de DetecçãoRESUMO
Cisplatin (DDP)-based combined chemotherapy or concurrent chemoradiotherapy is the mainstay treatment for advanced-stage nasopharyngeal carcinoma (NPC), but needs improvement due to its severe side effects. Capsaicin (CAP) can enhance the anti-tumor activity of cytotoxic drugs. The aim of this study was to investigate the anti-metastasis activity of CAP in combination with DDP in NPC. Herein, CAP and DDP showed synergistic cytotoxic effects on NPC cells. CAP alone and DDP alone inhibited NPC migration and invasion in vitro and in vivo, and the combination of CAP and DDP had the greatest effect. Moreover, CAP upregulated the mRNA and protein expressions of serpin family B member 2 (SERPINB2). Further results showed that both SERPINB2 mRNA and protein expressions were downregulated in NPC cell lines and tissues and SERPINB2 overexpression inhibited NPC migration and invasion in vitro and in vivo, while silencing SERPINB2 acted oppositely. In addition, SERPINB2 was abnormally expressed in head and neck squamous cell carcinoma and other multiple cancers, and downregulation of SERPINB2 predicted poor prognosis in head and neck squamous cell carcinoma according to the Cancer Genome Atlas database. We further found that SERPINB2 overexpression inhibited epithelial-mesenchymal transition (EMT) and the phosphorylated extracellular signal-regulated kinase (p-ERK), and the inhibitory effect was enhanced by CAP and DDP. Altogether, our results suggest that the combined inhibition of CAP and DDP on NPC metastasis may be related to the inhibition of epithelial-mesenchymal transition and ERK signals mediated by SERPINB2, and CAP may help to improve the efficacy of DDP in the treatment of NPC and develop new therapeutic approaches.
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Capsaicina , Movimento Celular , Cisplatino , Transição Epitelial-Mesenquimal , Sistema de Sinalização das MAP Quinases , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Inibidor 2 de Ativador de Plasminogênio , Humanos , Cisplatino/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/genética , Capsaicina/farmacologia , Capsaicina/uso terapêutico , Animais , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/genética , Camundongos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Inibidor 2 de Ativador de Plasminogênio/metabolismo , Inibidor 2 de Ativador de Plasminogênio/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Proliferação de Células/efeitos dos fármacos , Camundongos Nus , Sinergismo Farmacológico , Feminino , Camundongos Endogâmicos BALB CRESUMO
Pd(OAc)2/Nixantphos or CoI2/Nixantphos catalyzed allylic substitutions with weakly acidic C(sp)3-H bonds of azaarylmethylamines are described. This method facilitates access to various kinds of heteroaryl rings containing homoallylamines (39 examples, 30-98% yields) with excellent functional group tolerance and diastereoselectivity. Compared with the Pd/Nixantphos complex, the Co/Nixantphos catalysis could obtain the cyclic products with good to excellent diastereoselectivities. Importantly, the CoI2/(R,R)-Me-Duphos catalyzed reactions exhibit moderate enantioselectivity. Additionally, the scalability of this transformation is successfully demonstrated.
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Diffuse Large B-cell lymphoma (DLBCL) is a highly aggressive disease with heterogeneous outcomes and marked variability in the response to chemotherapy. DLBCL comprises two major subtypes: germinal centre B-cell-like (GCB) and activated B-cell-like (ABC). Our study highlights the extensive antitumour activity of artesunate (ART) against both major DLBCL subtypes. Transcriptome analysis suggests the potential involvement of ferroptosis in artesunate-induced cell death. Because of low glutathione (GSH) and glutathione peroxidase 4 (GPX4) levels, along with the accumulation of free iron (Fe2+), artesunate induces the excessive production of reactive oxygen species (ROS), ultimately leading to ferroptosis, a form of cell death driven by phospholipid peroxidation. A putative target of artesunate, metallothionein 1G (MT1G), was selected for further analysis. Subsequent studies revealed that inhibiting MT1G expression in vitro significantly impedes the ferroptosis-promoting activity of artesunate by reducing lipid peroxidation and iron accumulation. We also showed that the combination of artesunate and doxorubicin had a marked additive inhibitory effect on GCB and ABC DLBCL cells. In conclusion, artesunate induces ferroptotic death in GCB and ABC DLBCL cells by attenuating the GPX4/GSH antioxidant defence system and increasing intracellular iron levels, indicating its therapeutic potential for relapsed or refractory DLBCL.
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BACKGROUND: Vomiting is one of the most common adverse events of chemotherapy. The purpose of this study was to systematically review the clinical efficacy of acupoint injection of metoclopramide in the treatment of post-chemotherapy vomiting. METHODS: We searched 4 general English databases and 4 conventional Chinese databases, all with a time frame from database creation to December 2022. The retrieved clinical trials of acupoint injection of metoclopramide for post-chemotherapy vomiting were then subjected to meta-analysis and trial sequential analysis. RESULTS: A total of 12 studies were included, with a total sample size of 965 cases. Meta-analysis showed that acupoint injection of metoclopramide was effective in improving anti-vomiting effective rate [odds ratioâ =â 5.67, 95% confidence intervalâ =â (3.80,8.47), Pâ <â .00001] compared with intramuscular/intravenous injection, and trial sequential analysis showed that this benefit was conclusive. Subgroup analysis demonstrated that acupoint injection significantly improved the anti-vomiting effective rate at doses of 10 mg qd, 20 mg qd, and 30 mg qd, as well as at durations of 1 day and 5 days. Subgroup analysis also indicated that injection at the Zusanli acupoint significantly increased the anti-vomiting effective rate, while injection at the Neiguan acupoint had an anti-vomiting effective rate comparable to that of the control group. Harbord regression showed no significant publication bias (Pâ =â .730). CONCLUSION: Acupoint injection of metoclopramide for post-chemotherapy vomiting is more effective than intramuscular and intravenous injections and is not limited by dose or duration of treatment, which may be the preferred way of administration.
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Pontos de Acupuntura , Antieméticos , Antineoplásicos , Metoclopramida , Vômito , Metoclopramida/administração & dosagem , Metoclopramida/uso terapêutico , Humanos , Vômito/tratamento farmacológico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antieméticos/administração & dosagem , Antieméticos/uso terapêutico , Resultado do TratamentoRESUMO
An increasing body of research has demonstrated the significant role of long non-coding RNAs (lncRNAs) in the pathogenesis of stroke. They can actively contribute to the disease's progression either by directly participating in its pathogenesis or by acting as mediators through competing endogenous RNA (ceRNA) mechanisms. Concurrently, epigenetics plays a pivotal role in the pathological mechanisms underlying stroke. Epigenetic factors serve as valuable markers for disease progression, diagnostic biomarkers, and novel therapeutic targets. One of the most prevalent epigenetic modifications is 5-methylcytosine (m5C). However, the specific profiles of 5-methylcytosine in lncRNAs associated with stroke remain to be solved. Within the scope of this research, we performed a thorough transcriptome-wide analysis of m5C methylation within lncRNAs by methylated RNA immunoprecipitation sequencing (MeRIP-Seq), within a mouse stroke model induced by middle cerebral artery occlusion. Our findings reveal substantial disparities in both the quantity and distribution of m5C within the mouse stroke model compared to normal mice. This suggests a potential linkage between stroke and lncRNA m5C modifications, offering valuable insights into the mechanisms of stroke pathogenesis and the development of new drug targets.
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BACKGROUND: Nasopharyngeal carcinoma (NPC) is a complex cancer influenced by various factors. This study explores the use of single-cell Raman spectroscopy as a potential diagnostic tool for investigating biomolecular changes associated with NPC carcinogenesis. METHODS: Seven NPC cell lines, one immortalised nasopharyngeal epithelial cell line, six nasopharyngeal mucosa tissues and seven NPC tissue samples were analysed by performing confocal Raman spectroscopic measurements and imaging. The single-cell Raman spectral dataset was used to quantify relevant biomolecules and build machine learning classification models. Metabolomic profiles were investigated using ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS). RESULTS: By generating a metabolic map of seven NPC cell lines, we identified an interplay of altered metabolic processes involving nucleic acids, amino acids, lipids and sugars. The results from spatially resolved Raman maps and UPLC-MS/MS metabolomics were consistent, revealing an increase of unsaturated fatty acids in cancer cells, particularly in highly metastatic 5-8F and poorly differentiated CNE2 cells. The classification model achieved a nearly perfect classification when identifying NPC and non-NPC cells with an ROC-AUC of 0.99 and a value of 0.97 when identifying 13 tissue samples. CONCLUSION: This study unveils a complex interplay of metabolic network and highlights the potential roles of unsaturated fatty acids in NPC progression and metastasis. This renders further research to provide deeper insights into NPC pathogenesis, identify new metabolic targets and improve the efficacy of targeted therapies in NPC. Artificial intelligence-aided analysis of single-cell Raman spectra has achieved high accuracies in the classification of both cancer cells and patient tissues, paving the way for a simple, less invasive and accurate diagnostic test.
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Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Análise Espectral Raman , Humanos , Análise Espectral Raman/métodos , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/metabolismo , Linhagem Celular Tumoral , Inteligência Artificial , Análise de Célula Única/métodos , Metabolômica/métodos , Metaboloma , Espectrometria de Massas em Tandem/métodos , Aprendizado de MáquinaRESUMO
Overexpressed pro-survival B-cell lymphoma-2 (BCL-2) family proteins BCL-2 and BCL-XL can render tumor cells malignant. Leukemia drug venetoclax is currently the only approved selective BCL-2 inhibitor. However, its application has led to an emergence of resistant mutations, calling for drugs with an innovative mechanism of action. Herein we present cyclic peptides (CPs) with nanomolar-level binding affinities to BCL-2 or BCL-XL, and further reveal the structural and functional mechanisms of how these CPs target two proteins in a fashion that is remarkably different from traditional small-molecule inhibitors. In addition, these CPs can bind to the venetoclax-resistant clinical BCL-2 mutants with similar affinities as to the wild-type protein. Furthermore, we identify a single-residue discrepancy between BCL-2 D111 and BCL-XL A104 as a molecular "switch" that can differently engage CPs. Our study suggests that CPs may inhibit BCL-2 or BCL-XL by delicately modulating protein-protein interactions, potentially benefiting the development of next-generation therapeutics.
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Antineoplásicos , Peptídeos Cíclicos , Peptídeos Cíclicos/farmacologia , Proteína bcl-X/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Sulfonamidas/farmacologia , Antineoplásicos/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Apoptose , Linhagem Celular TumoralRESUMO
Sinomenine is a pure alkaloid isolated from Sinomenium acutum. This study is aimed to investigate the critical role of the nuclear factor erythroid 2-related factor 2 (Nrf2)-kelch-like ECH-associated protein-1(Keap1)-antioxidant response element (ARE) antioxidative signaling pathway in protecting sinomenine against H2O2-induced oxidative injury. Cytotoxicity and antioxidant experiments to initially determine the protective effects of sinomenine show that sinomenine has no effect on the decreased cell viability and presents similar potency in scavenging all three free radicals. The binding affinity between sinomenine and Keap1 was determined via fluorescence polarization assay, with IC50 of 13.52 µM. Quantum chemical calculation and theoretical simulation illustrated that sinomenine located into the Nrf2-binding site of Keap1 via hydrophobic and hydrogen interactions, showing high stability and binding affinity. On the basis of the stable binding of sinomenine with Keap1, sinomenine efficiently induced nuclear translocation of Nrf2, and increased in ARE activity in a concentration-dependent manner. Quantitative polymerase chain reaction provided further evidences that sinomenine-induced protection upregulated ARE-dependent genes, such as NAD(P)H quinone oxidoreductase 1, hemeoxygenase-1, and glutamate-cysteine ligase modiï¬er subunit. Western blot confirmed that sinomenine increased the expressions of these antioxidative enzymes. Taken together, in vitro and in silico evaluations demonstrate that sinomenine inhibits the binding of Keap1 to Nrf2, promotes the nuclear accumulation of Nrf2 and thus leads to the upregulated expressions of Nrf2-dependent antioxidative genes. Our findings also highlight the use of sinomenine for pharmacological or therapeutic regulation of the Nrf2-Keap1-ARE system, which is a novel strategy to prevent the progression of oxidative injury.
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Elementos de Resposta Antioxidante , Antioxidantes , Morfinanos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Peróxido de Hidrogênio/metabolismo , Estresse Oxidativo , NADH NADPH Oxirredutases/genéticaRESUMO
BACKGROUND/AIMS: Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin lymphoma, has significant prognostic heterogeneity. This study aimed to generate a prognostic prediction model based on autophagy-related genes for DLBCL patients. METHODS: Utilizing bioinformatics techniques, we analyzed the clinical information and transcriptome data of DLBCL patients from the Gene Expression Omnibus (GEO) database. Through unsupervised clustering, we identified new autophagy-related molecular subtypes and pinpointed differentially expressed genes (DEGs) between these subtypes. Based on these DEGs, a prognostic model was constructed using Cox and Lasso regression. The effectiveness, accuracy, and clinical utility of this prognostic model were assessed using numerous independent validation cohorts, survival analyses, receiver operating characteristic (ROC) curves, multivariate Cox regression analysis, nomograms, and calibration curves. Moreover, functional analysis, immune cell infiltration, and drug sensitivity analysis were performed. RESULTS: DLBCL patients with different clinical characterizations (age, molecular subtypes, ECOG scores, and stages) showed different expression features of autophagy-related genes. The prediction model was constructed based on the eight autophagy-related genes (ADD3, IGFBP3, TPM1, LYZ, AFDN, DNAJC10, GLIS3, and CCDC102A). The prognostic nomogram for overall survival of DLBCL patients incorporated risk level, stage, ECOG scores, and molecular subtypes, showing excellent agreement between observed and predicted outcomes. Differences were noted in the proportions of immune cells (native B cells, Treg cells, CD8+ T cell, CD4+ memory activated T cells, gamma delta T cells, macrophages M1, and resting mast cells) between high-risk and low-risk groups. LYZ and ADD3 exhibited correlations with drug resistance to most chemotherapeutic drugs. CONCLUSIONS: This study established a novel prognostic assessment model based on the expression profile of autophagy-related genes and clinical characteristics of DLBCL patients, explored immune infiltration and predicted drug resistance, which may guide precise and individualized immunochemotherapy regimens.
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Linfoma Difuso de Grandes Células B , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Autofagia/genética , Probabilidade , Linfócitos B , Resistência a Medicamentos , Prognóstico , Proteínas de Ligação a CalmodulinaRESUMO
A nickel-catalyzed cross-electrophile coupling of aryl iodides with α-bromo sulfoxide to access a diverse array of aryl benzyl sulfoxides has been discovered. These reactions occurred under mild conditions with excellent functional group tolerance so that optically enriched sulfoxides could be coupled with aryl iodides, generating corresponding sulfoxides with excellent stereochemical integrity. Furthermore, the scalability of this transformation was demonstrated. Initial mechanistic studies revealed that the reaction undergoes a radical pathway.
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IMPORTANCE: The development of safe and effective vaccines is needed to control the transmission of coronavirus disease 2019 (COVID-19). Synthetic DNA vaccines represent a promising platform in response to such outbreaks. Here, DNA vaccine candidates were developed using an optimized antibiotic-resistance gene-free asd-pVAX1 vector. An optimized flagellin (FliC) adjuvant was designed by fusion expression to increase the immunogenicity of the S1 antigen. S1 and S1-FliCΔD2D3 proteins were strongly expressed in mammalian cells. The FliCΔD2D3-adjuvanted DNA vaccine induced Th1/Th2-mixed immune responses and high titers of neutralizing antibodies. This study provides crucial information regarding the selection of a safer DNA vector and adjuvant for vaccine development. Our FliCΔD2D3-adjuvanted S1 DNA vaccine is more potent at inducing both humoral and cellular immune responses than S1 alone. This finding provides a new idea for the development of novel DNA vaccines against COVID-19 and could be further applied for the development of other vaccines.
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COVID-19 , Vacinas de DNA , Humanos , Animais , Camundongos , Salmonella typhimurium/metabolismo , Vacinas de DNA/genética , Vacinas de DNA/metabolismo , SARS-CoV-2 , Flagelina/genética , Flagelina/metabolismo , Vacinas contra COVID-19 , COVID-19/prevenção & controle , Adjuvantes Imunológicos/metabolismo , Adjuvantes Imunológicos/farmacologia , Anticorpos Neutralizantes/metabolismo , Anticorpos Antivirais/metabolismo , Imunogenicidade da Vacina , MamíferosRESUMO
BACKGROUND: Due to its unique fingerprinting properties, Confocal Raman microscopy (CRM) can be used to examine the biomolecular changes of viruses invading and manipulating host cells. Recently, the biochemical changes due to the invasion and infection of B lymphocyte cells, nerve cells, and epithelial cells by Epstein-Barr virus (EBV) have been reported. However, biomolecular changes in nasopharyngeal epithelial cells that result from EBV infection are still poorly understood. METHODS: In continuation of our prior investigation of EBV infection in nasopharyngeal epithelial cells, we tried to expound on biomolecular changes in EBV-infected nasopharyngeal epithelial cells using Raman microspectroscopy. EBV has two life cycles, latent infection and lytic replication. We have established latent and lytic infection models at the cellular level. In order to understand the characteristics of the two patterns of EBV infection, we used Raman spectroscopy to identify the changes in biomolecules of EBV latent cells (CNE2, CNE2-EBV) and lytic cells (NPEC1-BMI1-CN, NPEC1-BMI1-EBV). RESULTS: During latent infection, levels of glycogen, protein, and lipid molecules in the cell increased while levels of nucleic acid and collagen molecules decreased. Molecular levels of glycogen, proteins, and nucleic acids are reduced during lytic infection. We found that molecular levels of nucleic acid decreased during two different periods of infection, whereas levels of other biomolecules showed the opposite trend. Glycogen, proteins, lipids, nucleic acids, and other molecules are associated with alterations in cellular biochemical homeostasis. These changes correspond to unique Raman spectra in infected and uninfected cells associated with specific biomolecules that have been proven. These molecules are mainly responsible for cellular processes such as cell proliferation and apoptosis. The Raman signatures of these biomolecular changes depend on the different phases of viral infection. CONCLUSIONS: Therefore, by using CRM, it is possible to discern details in the progression of EBV infection in nasopharyngeal epithelial cells at the molecular level.
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Infecções por Vírus Epstein-Barr , Infecção Latente , Ácidos Nucleicos , Humanos , Herpesvirus Humano 4/fisiologia , Células Epiteliais/metabolismo , Infecção Latente/metabolismo , Glicogênio/metabolismo , Ácidos Nucleicos/metabolismoRESUMO
The first dual nickel/photoredox-catalyzed enantioselective reductive cross-coupling of racemic α-chloro thioesters with aryl iodides has been developed. This strategy avoids the need for organometallic reagents or stoichiometric metal reductants. This reaction could tolerate a wide range of substrate scope with excellent reactivity and high enantioselectivities (up to 91% ee) to access a variety of chiral α-aryl thioesters. The synthetic utility of the corresponding α-aryl thioesters is demonstrated. Furthermore, we explored the mechanism of such an enantioselective radical cross-coupling process.