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1.
Ann Med ; 54(1): 3177-3188, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36351877

RESUMO

Objective: An increasing number of studies suggest that sleep disordered breathing (SDB) may be associated with postoperative atrial fibrillation (POAF), but these studies present discrepant results. Thus, this meta-analysis aimed to synthesize the data associating SDB with POAF in patients who underwent cardiac surgery.Methods: A literature search was performed in the Scopus, PubMed, Web of Science, EMBASE, CENTRAL, Weipu, Wanfang Data, and China National Knowledge Infrastructure databases before August 2022. Data were extracted, and the strength of the relationship between SDB and the risk of POAF was evaluated using odds ratio (OR) and 95% confidence intervals (CIs). All statistical analysis was carried out using the Stata 12.0 software.Results: A total of 24 studies with 660,685 subjects were included in current meta-analysis. SDB was significantly associated with the risk of POAF in the patients who underwent cardiac surgery (OR = 1.49; 95% CI, 1.30-1.70; p < .001). Next subgroup analysis revealed that such association may be increased in the group with medical equipment-measured SDB (OR = 2.27; 95% CI, 1.59-3.23; p < .001), prospective studies (OR = 2.17; 95% CI, 1.55-3.03; p < .001), patients without a previous history of atrial fibrillation (OR = 2.04; 95% CI, 1.47-2.82; p < .001), and patients who received a coronary artery bypass graft (OR = 2.10; 95% CI, 1.45-3.05; p < .001). No publication bias was identified.Conclusion: The results of meta-analysis support that SDB may be associated with an increased risk of POAF in patients who had undergone cardiac surgery, and these results should be confirmed in more rigorously designed studies.KEY MESSAGESPatients with SDB who underwent cardiac surgery showed increased risk of POAF.The relationship between SDB and POAF should be explained with caution with the consideration of various covariate.The effect of pre-treatment of SDB on POAF should be examined in future.


Assuntos
Fibrilação Atrial , Procedimentos Cirúrgicos Cardíacos , Síndromes da Apneia do Sono , Humanos , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Estudos Prospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/epidemiologia , Fatores de Risco
2.
Org Lett ; 24(43): 7983-7987, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36300950

RESUMO

A direct acetylation of inert C(sp3)-H bonds was developed that was catalyzed by decatungstate under visible light irradiation and was followed by radical addition-disassociation with phenylsulfonyl ethanone oxime. The reaction displays site-selectivity in multiple C(sp3)-H bonds without prefunctionalization and directing groups. Various functional groups are well-tolerated and natural molecules are structurally feasible. CF3-modified phenylsulfonyl ethanone oxime was discovered to be necessary for enhancing the electrophilicity of imine and lowering the C-S bond cleavage energy.


Assuntos
Oximas , Catálise , Acetilação
3.
Front Immunol ; 13: 940779, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36203605

RESUMO

Background: A major challenge in intervention of critical patients, especially sepsis-associated delirium (SAD) intervention, is the lack of predictive risk factors. As sepsis and SAD are heavily entangled with inflammatory and immunological processes, to identify the risk factors of SAD and mortality in the intensive care unit (ICU) and determine the underlying molecular mechanisms, the peripheral immune profiles of patients in the ICU were characterized. Methods: This study contains a cohort of 52 critical patients who were admitted to the ICU of the First Affiliated Hospital of Jinan University. Comorbidity, including sepsis and SAD, of this cohort was diagnosed and recorded. Furthermore, peripheral blood samples were collected on days 1, 3, and 5 of admission for peripheral immune profiling with blood routine examination, flow cytometry, ELISA, RNA-seq, and qPCR. Results: The patients with SAD had higher mortality during ICU admission and within 28 days of discharge. Compared with survivors, nonsurvivors had higher neutrophilic granulocyte percentage, higher CRP concentration, lower monocyte count, lower monocyte percentage, lower C3 complement level, higher CD14loCD16+ monocytes percentage, and higher levels of IL-6 and TNFα. The CD14hiCD16- monocyte percentage manifested favorable prediction values for the occurrence of SAD. Differentially expressed genes between the nonsurvival and survival groups were mainly associated with immune response and metabolism process. The longitudinal expression pattern of SLC2A1 and STIMATE were different between nonsurvivors and survivors, which were validated by qPCR. Conclusions: Nonsurvival critical patients have a distinct immune profile when compared with survival patients. CD14hiCD16- monocyte prevalence and expression levels of SLC2A1 and STIMATE may be predictors of SAD and 28-day mortality in ICU patients.


Assuntos
Encefalopatia Associada a Sepse , Sepse , Complemento C3 , Humanos , Unidades de Terapia Intensiva , Interleucina-6 , Fatores de Risco , Sepse/metabolismo , Fator de Necrose Tumoral alfa
4.
Genet Res (Camb) ; 2022: 8429207, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36062065

RESUMO

Background: Assays of transposase accessible chromatin sequencing (ATAC-seq) is an efficient assay to investigate chromatin accessibility, which depends on the activity of a robust Tn5 transposase to fragment the genome while cutting in the sequencing adapters. Methods: We propose reliable approaches for purifying hyperactive Tn5 transposase by chitin magnetic bead sorting. Double-stranded DNA of J76 cells and 293T cells were digested and subjected to tagmentation as test samples with Tn5 transposase, and libraries were established and sequenced. Sequencing data was then analyzed for peak calling, GO enrichment, and motif analysis. Results: We report a set of rapid, efficient, and low-cost methods for ATAC-seq library construction and data analysis, through large-scale and rapid sequencing. These methods can provide a reference for the study of epigenetic regulation of gene expression.


Assuntos
Sequenciamento de Cromatina por Imunoprecipitação , Sequenciamento de Nucleotídeos em Larga Escala , Cromatina/genética , Epigênese Genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de DNA/métodos , Tecnologia , Transposases/genética , Transposases/metabolismo
5.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 34(7): 759-761, 2022 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-36100417

RESUMO

With the widespread application of extracorporeal membrane oxygenation (ECMO) technology, ECMO centers have been established in most regions of China, and the demand for ECMO transport is also increasing. Critically ill patients with ECMO carry many catheters. ECMO devices and accessories are cumbersome and numerous, requiring a large amount of manpower to assist in the transfer. At present, most of ECMO transport equipment are vertical carts provided by equipment suppliers, which cannot accommodate all ancillary equipment and are difficult to be loaded into ambulances for transportation. Therefore, critically ill patients face many risks if they need to be transported inter-hospital. A specific vehicle for ECMO patients was designed by the medical staff of the department of critical care medicine of Zhujiang Hospital of Southern Medical University, which integrates the ECMO host, oxygenator, centrifugal pump, portable ventilator, coagulation instrument, injection pump, monitor, oxygen cylinder, and etc., to greatly facilitate the transportionation. This invention obtained the National Utility Model Patent of China (ZL 2019 2 1201261.4). The new ECMO transport vehicle can facilitate the interhospital transport of critically ill patients, reduce the occurrence of accidents, shorten the transport time and reduce the number of transport personnel, and has a good clinical application value.


Assuntos
Oxigenação por Membrana Extracorpórea , Ambulâncias , Estado Terminal , Humanos , Transferência de Pacientes , Estudos Retrospectivos
6.
Front Mol Biosci ; 9: 942402, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052170

RESUMO

Background: An imbalance in the redox homeostasis has been reported in multiple cancers and is associated with a poor prognosis of disease. However, the prognostic value of redox-related genes in non-small-cell lung cancer (NSCLC) remains unclear. Methods: RNA sequencing data, DNA methylation data, mutation, and clinical data of NSCLC patients were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. Redox-related differentially expressed genes (DEGs) were used to construct the prognostic signature using least absolute shrinkage and selection operator (LASSO) regression analysis. Kaplan-Meier survival curve and receiver operator characteristic (ROC) curve analyses were applied to validate the accuracy of the gene signature. Nomogram and calibration plots of the nomogram were constructed to predict prognosis. Pathway analysis was performed using gene set enrichment analysis. The correlations of risk score with tumor stage, immune infiltration, DNA methylation, tumor mutation burden (TMB), and chemotherapy sensitivity were evaluated. The prognostic signature was validated using GSE31210, GSE26939, and GSE68465 datasets. Real-time polymerase chain reaction (PCR) was used to validate dysregulated genes in NSCLC. Results: A prognostic signature was constructed using the LASSO regression analysis and was represented as a risk score. The high-risk group was significantly correlated with worse overall survival (OS) (p < 0.001). The area under the ROC curve (AUC) at the 5-year stage was 0.657. The risk score was precisely correlated with the tumor stage and was an independent prognostic factor for NSCLC. The constructed nomogram accurately predicted the OS of patients after 1-, 3-, and 5-year periods. DNA replication, cell cycle, and ECM receptor interaction were the main pathways enriched in the high-risk group. In addition, the high-risk score was correlated with higher TMB, lower methylation levels, increased infiltrating macrophages, activated memory CD4+ T cells, and a higher sensitivity to chemotherapy. The signature was validated in GSE31210, GSE26939, and GSE68465 datasets. Real-time PCR validated dysregulated mRNA expression levels in NSCLC. Conclusions: A prognostic redox-related gene signature was successfully established in NSCLC, with potential applications in the clinical setting.

7.
Can Respir J ; 2022: 7078652, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36124285

RESUMO

Adenosine deaminase 2 (ADA2) is reported as a novel diagnostic biomarker for tuberculous pleural effusion (TPE) in many studies. This meta-analysis was conducted to systematically evaluate the general diagnostic performance of pleural ADA2 in TPE. After searching for relevant studies that investigated the diagnostic performance of pleural ADA2 in TPE in several databases, we assessed and selected eligible studies to calculate pooled parameters by STATA 16.0 software. A final set of thirteen studies entirely met the inclusion standards and were used to calculate pooled parameters in our meta-analysis. Among them, there were nine English studies and four Chinese studies. The pooled parameters of pleural ADA2 in diagnosing TPE were summarized as follows: sensitivity, 0.91 (95% CI: 0.86-0.95); specificity, 0.93 (95% CI: 0.92-0.95); positive likelihood ratio, 13.9 (95% CI: 10.6-18.3); negative likelihood ratio, 0.09 (95% CI:0.06-0.16); diagnostic odds ratio, 147 (95% CI: 76-284); and the area under the curve, 0.95 (95% CI: 0.93-0.97). Pleural ADA2 is a reliable indicator with excellent accuracy in TPE diagnosis. However, we need to combine pleural ADA2 with diverse examinations to diagnose TPE in clinical practice.


Assuntos
Derrame Pleural , Tuberculose Pleural , Adenosina Desaminase , Biomarcadores/análise , Humanos , Razão de Chances , Derrame Pleural/diagnóstico , Tuberculose Pleural/diagnóstico
8.
Front Oncol ; 12: 922604, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36081552

RESUMO

Accumulating evidence indicates that liquid-liquid phase separation (LLPS) is the basis of the formation of membrane-less compartments in cells. This biomolecular condensate represented by phase separation may influence epigenetics in cancer stem cells (CSCs), a small subpopulation of cancer cells responding to the initiation, maintenance, metastasis, and therapy resistance of cancer. Understanding the underlying biophysical principles and the specific characteristics of biocondensates would provide insights into the precise blocking of potential tumor targets, thereby fundamentally curbing tumor occurrence, recurrence and metastasis. In this review, we summarized the key phenomenon and experimental detection of phase separation and the possibility of regulating the stemness of CSCs through phase separation. We believe that the mechanism of phase separation in CSCs will open up new avenues for the mystery of tumor formation, and modulating phase separation will be a great strategy for CSC-targeted tumor therapy.

9.
BMC Cancer ; 22(1): 1016, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36162993

RESUMO

BACKGROUND: Bladder cancer (BLCA) is one of the most common genitourinary malignancies in the world, but its pathogenic genes have not been fully identified and the treatment outcomes are still unsatisfactory. Although the members of 2', 5'-oligoadenylate synthetase (OAS) gene family are known involved in some tumorous biological processes, the roles of the OAS gene family in BLCA are still undetermined. METHODS: By combining vast bioinformatic datasets analyses of BLCA and the experimental verification on clinical BLCA specimen, we identified the expressions and biological functions of OAS gene family members in BLCA with comparison to normal bladder tissues. RESULTS: The expression levels of OAS gene family members were higher in BLCA than in normal bladder tissues. The expression levels of most OAS genes had correlations with genomic mutation and methylation, and with the infiltration levels of CD4 + T cells, CD8 + T cells, neutrophils, and dendritic cells in the microenvironment of BLCA. In addition, high expressions of OAS1, OAS2, OAS3, and OASL predicted better overall survival in BLCA patients. CONCLUSIONS: The highly expressed OAS genes in BLCA can reflect immune cells infiltration in the tumor microenvironment and predict the better overall survival of BLCA, and thus may be considered as a signature of BLCA. The study provides new insights into the diagnosis, treatment, and prognosis of BLCA.


Assuntos
2',5'-Oligoadenilato Sintetase , Neoplasias da Bexiga Urinária , 2',5'-Oligoadenilato Sintetase/genética , Nucleotídeos de Adenina , Humanos , Ligases , Oligorribonucleotídeos , Prognóstico , Microambiente Tumoral/genética , Neoplasias da Bexiga Urinária/genética
10.
J Transl Med ; 20(1): 392, 2022 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-36059026

RESUMO

BACKGROUND: Fibroproliferative repair starts early in the inflammatory phase of acute respiratory distress syndrome (ARDS) and indicates a poor prognosis. Lumican, a small leucine-rich proteoglycan, is implicated in homeostasis and fibrogenesis, but its role in ARDS is unclear. METHODS: Bronchoalveolar lavage fluid (BALF) samples were obtained from ARDS patients (n = 55) enrolled within 24 h of diagnosis and mechanically ventilated (n = 20) and spontaneously breathing (n = 29) control subjects. Lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse models were intratracheally administered an adeno-associated virus (AAV) vector expressing lumican shRNA. Primary human lung fibroblasts (HLF) and small airway epithelial cells (SAECs) were cultured with tumour necrosis factor (TNF)-α or lumican. Luminex/ELISA, histochemistry/immunohistochemistry, immunofluorescence microscopy, quantitative real-time PCR, and western blotting were performed. RESULTS: Lumican levels were significantly higher in the BALF of ARDS patients than in that of ventilated or spontaneously breathing controls (both p < 0.0001); they were correlated with the PaO2/FiO2 ratio and levels of proinflammatory cytokines (interleukin-6, interleukin-8, and TNF-α) and profibrotic factors (fibronectin, alpha-1 type I collagen [COL1A1], and alpha-1 type III collagen [COL3A1]). Lumican expression was enhanced in the alveolar walls and airway epithelium in the ALI mouse model. Murine lumican levels were also linked to proinflammatory and profibrotic cytokine levels in the BALF. In vitro, TNF-α induced the synthesis and secretion of lumican in HLF. In turn, lumican increased the expression of alpha-smooth muscle actin (α-SMA), COL1A1, and COL3A1 in HLF, upregulated α-SMA and COL3A1, downregulated E-cadherin, and caused spindle-shaped morphological changes in SAECs. Moreover, increased ERK phosphorylation and Slug were noted in both HLF and SAECs treated with lumican. In vivo, AAV-mediated knockdown of lumican inhibited the pulmonary production of fibronectin and COL3A1 and alleviated lung fibrotic lesions in LPS-challenged mice. CONCLUSIONS: Pulmonary lumican levels were increased early in human and experimental ARDS and linked to disease severity and inflammatory fibrotic processes. Lumican triggers the transdifferentiation of lung fibroblasts into myofibroblasts and epithelial-mesenchymal transition in SAECs, possibly via the ERK/Slug pathway. Knockdown of pulmonary lumican attenuated extracellular matrix deposition in ALI mice. Overall, lumican promotes fibrotic responses in the early phase of ARDS, suggesting its potential as a therapeutic target.


Assuntos
Lesão Pulmonar Aguda , Lumicana/metabolismo , Síndrome do Desconforto Respiratório , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Modelos Animais de Doenças , Fibronectinas , Fibrose , Humanos , Lipopolissacarídeos/metabolismo , Pulmão/patologia , Camundongos , Síndrome do Desconforto Respiratório/patologia , Fator de Necrose Tumoral alfa/metabolismo
11.
Langmuir ; 38(37): 11137-11148, 2022 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-36070512

RESUMO

Understanding the behaviors of nanoparticles at interfaces is crucial not only for the design of novel nanostructured materials with superior properties but also for a better understanding of many biological systems where nanoscale objects such as drug molecules, viruses, and proteins can interact with various interfaces. Theoretical studies and tailored computer simulations offer unique approaches to investigating the evolution and formation of structures as well as to determining structure-property relationships regarding the interfacial nanostructures. In this feature article, we summarize our efforts to exploit computational approaches as well as theoretical modeling in understanding the organization of nanoscale objects at the interfaces of various systems. First, we present the latest research advances and state-of-the-art computational techniques for the simulation of nanoparticles at interfaces. Then we introduce the applications of multiscale modeling and simulation methods as well as theoretical analysis to explore the basic science and the fundamental principles in the interfacial nanoparticle organization, covering the interfaces of polymer, nanoscience, biomacromolecules, and biomembranes. Finally, we discuss future directions to signify the framework in tailoring the interfacial organization of nanoparticles based on the computational design. This feature article could promote further efforts toward fundamental research and the wide applications of theoretical approaches in designing interfacial assemblies for new types of functional nanomaterials and beyond.


Assuntos
Nanopartículas , Nanoestruturas , Simulação por Computador , Modelos Teóricos , Nanopartículas/química , Nanoestruturas/química , Polímeros/química
12.
Cell Mol Biol (Noisy-le-grand) ; 68(3): 213-220, 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35988186

RESUMO

Nano-carbon is often used as a tracer in thyroidectomy, to improve the accuracy of the operation. Remifentanil is the most commonly used anesthetic during thyroidectomy, but the use of remifentanil can sometimes cause patients with anesthesia hyperalgesia. Therefore, auxiliary anesthetics are often used in surgery to prevent remifentanil from causing anesthesia hyperalgesia. The purpose of this article is to explore the specific application effect of the fusion agent of hydromorphone and parecoxib sodium after thyroidectomy based on nano-carbon in the prevention of remifentanil-induced anesthesia hyperalgesia. Taking 60 patients who underwent thyroidectomy based on carbon nanotechnology in our hospital as the research object, the patients were divided into the parecoxib sodium group, hydromorphone control group and hydromorphone and parecoxib sodium fusion agent group. All patients were injected with remifentanil before surgery for general paralysis. Ten minutes before the end of the operation, the parecoxib sodium group was injected with quantitative parecoxib sodium, and the hydromorphone control group was injected with quantitative hydromorphone, hydromorphone and the parecoxib sodium fusion medicament group was injected with a quantitative combination of parecoxib sodium and hydromorphone. The patient's comfort, calmness, pain, adverse reactions and recovery time of consciousness were counted. The results of the study showed that the sedation score of the hydromorphone and parecoxib sodium fusion drug group was (15.8±1.5), the pain degree score was (1.9±0.5), lower than the other two groups, and the postoperative recovery time was (38±5.0) )min, lower than the other two groups. It can be seen that the use of a fusion agent of hydromorphone and parecoxib sodium after thyroidectomy based on nano-carbon is effective in preventing and reducing remifentanil-induced anesthesia hyperalgesia.


Assuntos
Anestesia , Hiperalgesia , Analgésicos Opioides/efeitos adversos , Humanos , Hidromorfona/uso terapêutico , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Hiperalgesia/prevenção & controle , Isoxazóis , Dor/induzido quimicamente , Piperidinas/uso terapêutico , Remifentanil/efeitos adversos , Tireoidectomia/efeitos adversos
13.
Artigo em Inglês | MEDLINE | ID: mdl-35873643

RESUMO

Purpose: The ripe fruits of Citrus changshan-huyou, known as Quzhou Fructus Aurantii (QFA), have been commonly used for respiratory diseases. The purpose of this study was to investigate their active compounds and demonstrate their mechanism in the treatment of upper respiratory tract infections (URTIs) through network pharmacology and molecular docking. Methods: The prominent compounds of QFA were acquired from TCMSP database. Their targets were retrieved from SwissTargetPrediction database, and target genes associated with URTIs were collected from DisGeNET and GeneCards databases. The target protein-protein interaction (PPI) network was constructed by using STRING database and Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were enriched. Visual compound-target-pathway network was established with Cytoscape. The effects of compounds were verified on the inhibitory activities against phosphoinositide 3-kinases (PI3Ks). Finally, the molecular docking was carried out to confirm the binding affinity of the bioactive compounds and target proteins. Results: Five important active compounds, naringenin (NAR), tangeretin (TAN), luteolin (LUT), hesperetin (HES), and auraptene (AUR), were obtained. The enrichment analysis demonstrated that the pathways associated with inflammation mainly contained PI3K/Akt signalling pathway, TNF signalling pathway, and so on. The most important targets covering inflammation-related proteins might be PI3Ks. In vitro assays and molecular docking exhibited that TAN, LUT, and AUR acted as PI3Kγ inhibitors. Conclusion: The results revealed that QFA could treat URTIs through a multi-compound, multi-target, multi-pathway network, in which TAN, LUT, and AUR acted as PI3Kγ inhibitors, probably contributing to a crucial role in treatment of URTIs.

14.
Toxicology ; 477: 153251, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35787437

RESUMO

Cigarette smoke (CS) mediates inflammation and epithelial-mesenchymal transition (EMT) in bronchial epithelial cells, contributing to airway remodeling in chronic obstructive pulmonary disease (COPD). Cross-talk between metabolic pathways and cell signaling has emerged as an important focus of research in the field of inflammation. Here, we established in vitro and in vivo models of CS-induced COPD to elucidate the role of pyruvate kinase M2 (PKM2), a glycolytic enzyme, in CS-induced airway remodeling. Exposure to CS significantly increased PKM2 expression in lung tissues of C57BL/6 mice and BEAS-2B cells, which positively related to the levels of airway inflammation and EMT. Administering PKM2 inhibitor shikonin attenuated CS-induced airway inflammation and EMT process. Moreover, knockdown of PKM2 by small-interfering RNA (siRNA) decreased the release of TNF-α and IL-8, ROS and reversed the CS extract (CSE)-induced changes of N-cadherin and E-cadherin in BEAS-2B cells. In CSE-treated cells, we also observed enhancement of PINK1/Parkin-mediated mitophagy, which were decreased by PKM2 siRNA. Furthermore, pretreatment with mitophagy inducer CCCP before CSE stimulation led to increased expressions of both nuclear and cytosolic PKM2, accompanied by reduction of TGF-ß-induced factor homeobox 2 (TGIF2), a repressor of TGF-ß1/smad pathway and EMT, while PKM2 knockdown restored the expression of TGIF2. Our results imply that CS induces PKM2 upregulation in airway epithelial cells, acting in synergism with PINK/Parkin-mediated mitophagy, which may initiate and exaggerate airway inflammation and EMT process. Further studies will be required to elucidate more molecular details and other pathways by which PKM2-mitophagy signaling regulates the effector function of airway epithelial.


Assuntos
Fumar Cigarros , Doença Pulmonar Obstrutiva Crônica , Remodelação das Vias Aéreas , Animais , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal , Inflamação/induzido quimicamente , Camundongos , Camundongos Endogâmicos C57BL , Mitofagia , Proteínas Quinases , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/metabolismo , Piruvato Quinase/genética , RNA Interferente Pequeno , Tabaco/genética , Ubiquitina-Proteína Ligases/genética
15.
Nat Commun ; 13(1): 4094, 2022 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-35835763

RESUMO

Diffusion transport of nanoparticles in confined environments of macromolecular networks is common in diverse physical systems and regulates many biological responses. Macromolecular networks possess various topologies, featured by different numbers of degrees and genera. Although the network topologies can be manipulated from a molecular level, how the topology impacts the transport of nanoparticles in macromolecular networks remains unexplored. Here, we develop theoretical approaches combined with simulations to study nanoparticle transport in a model system consisting of network cells with defined topologies. We find that the topology of network cells has a profound effect on the free energy landscape experienced by a nanoparticle in the network cells, exhibiting various scaling laws dictated by the topology. Furthermore, the examination of the impact of cell topology on the detailed behavior of nanoparticle dynamics leads to different dynamical regimes that go beyond the particulars regarding the local network loop. The results might alter the conventional picture of the physical origin of transport in networks.


Assuntos
Modelos Biológicos , Nanopartículas , Difusão , Substâncias Macromoleculares
16.
J Proteomics ; 266: 104667, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-35788409

RESUMO

Lysine malonylation, a novel identified protein posttranslational modification (PTM), is conservative and present in both eukaryotic and prokaryotic cells. Previous studies have reported that malonylation plays an important role in inflammation, angiogenesis, and diabetes. However, its potential role in cardiac remodeling remains unknown. Here, we observed a reduced lysine malonylation in hypertrophic mice hearts created by transverse aortic constriction (TAC) for 8 weeks. We also detected a decreased lysine malonylation in hypertrophic H9C2 cardiomyocytes induced by angiotensin II for 48 h. Using a proteomic method based on affinity purification and LC-MS/MS, we identified total 679 malonylated sites in 330 proteins in the hearts of sham mice and TAC mice. Bioinformatic analysis of the proteomic data revealed enrichment of malonylated proteins involved in cardiac structure and contraction, cGMP-PKG pathway, and metabolism. Specifically, we detected a decreased lysine malonylation in myocardial isocitrate dehydrogenase 2 (IDH2) by immunoprecipitation coupled with Western blotting both in vivo and in vitro. Together, our work suggests an important role and implication of protein lysine malonylation in cardiac hypertrophy, especially the IDH2. SIGNIFICANCE: Heart failure is the terminal stage of cardiac hypertrophy, which imposes an enormous clinical and economic burden worldwide. Despite our knowledge on the pathophysiology of the disease, current therapeutic approaches are still largely limited. Cardiac hypertrophy can be regulated at post-translational modifications (PTMs), and several PTMs have been reported in cardiac hypertrrophy and heart failure. In our study, we first reported a novel PTMs, lysine malonylation, in cardiac hypertophy. we found a reduced lysine malonylation in hypertrophic mice hearts in vivo and H9C2 cardiomyocytes after stimulating with angiotensinII for 48 h in vitro. Using affinity purification and LC-MS/MS, we identified 679 malonylated sites in 330 proteins in the hearts of sham and TAC mice. Compared to the sham group, 5 sites in 2 proteins were quantified as downregulated targets using a 2-fold threshold (downregulation <0.5-fold, P < 0.05). Functional analysis showed a significant enrichment in cardiac structure and contraction, cGMP-PKG pathway and metabolism. Notably, we identified a decreased Kmal level in isocitrate dehydrogenase 2 (IDH2), but the protein level of IDH2 has no changed in cardiac hypertrophy, These results highlight that lysine malonylation is associated with cardiac hypertrophy, and may be a new therapeutic target of the disease.


Assuntos
Insuficiência Cardíaca , Lisina , Animais , Cardiomegalia , Cromatografia Líquida , Humanos , Isocitrato Desidrogenase , Lisina/metabolismo , Malonatos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Proteínas/metabolismo , Proteômica/métodos , Espectrometria de Massas em Tandem
17.
Front Oncol ; 12: 884334, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35719943

RESUMO

Background: OAS gene family plays an important role in antiviral process, but its role in pancreatic cancer has not yet been studied. Methods: We analyzed the expression, prognostic value and biological function of the OAS gene family in human pancreatic cancer through comprehensive bioinformatic analysis and cellular level validation. Results: OAS family was highly expressed in pancreatic cancer, and this high expression significantly affected the clinical stage and prognosis of the tumor. OAS gene family was closely related to the immune infiltration of pancreatic cancer, especially neutrophils and dendritic cells, and many immune-related factors and pathways are enriched in the tumor, such as type I interferon signaling pathway and NOD-like receptor signaling pathway. Conclusion: Taken together, high expression of OAS family is closely related to poor prognosis of pancreatic cancer. OAS gene family may serve as the biomarker and even therapeutic target of pancreatic cancer.

18.
Drug Dev Res ; 83(5): 1201-1211, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35656621

RESUMO

Colorectal cancer (CRC) is one of the most common gastrointestinal cancers worldwide. This complex and often fatal disease has a high mortality rate. The Hedgehog (Hh) signaling pathway is crucial in CRC. Many studies have indicated that Shh is overexpressed in cancer stem cells (CSCs), and shh overexpression is positively correlated with CRC tumorigenesis. New drugs that kill CRC cells through the Hh pathway are needed. Toosendanin (TSN), a natural triterpenoid saponin extracted from the bark or fruit of Melia toosendan Sieb. et Zucc, can inhibit various tumors. Here, we investigated the effects of TSN in CRC and explored the possible targets and mechanisms. Shh-Light Ⅱ cells were treated with TSN and tested by dual luciferase reporter assays to determine the relationship with the Hh pathway. Cell Counting Kit-8 (CCK-8) assays were used to test the inhibitory effects of TSN on CRC cells. The expression of Hh components after TSN treatment was detected using western blots and quantitative reverse transcription polymerase chain reaction. Cellular thermal shift assays confirmed the targets of TSN. The same effects of TSN on xenograft tumor growth were investigated in vivo. The average weight, volume of the finally resected tumor, and the expression of Shh in the TSN-treated groups were significantly lower than those of the control group. This result strongly suggested that TSN administration inhibited CRC growth in vivo. Our research preliminarily demonstrated that the target of TSN was Shh and that TSN inhibits CRC cell growth by inhibiting the Hh pathway, identifying a new anticancer molecular mechanism of TSN in CRC.


Assuntos
Neoplasias Colorretais , Medicamentos de Ervas Chinesas , Apoptose , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Proteínas Hedgehog , Humanos , Triterpenos
19.
Nanoscale Horiz ; 7(9): 1016-1028, 2022 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-35762392

RESUMO

Entropy can be the sole driving force for the construction and regulation of ordered structures of soft matter systems. Specifically, under confinement, the entropic penalty could induce enhanced entropic effects which potentially generate visually ordered structures. Therefore, spatial confinement or a crowding environment offers an important approach to control entropy effects in these systems. Here, we review how spatial confinement-mediated entropic effects accurately and even dynamically control the self-assembly of nanoscale objects into ordered structures, focusing on our efforts towards computer simulations and theoretical analysis. First, we introduce the basic principle of entropic ordering through confinement. We then introduce the applications of this concept to various systems containing nanoparticles, including polymer nanocomposites, biological macromolecular systems and macromolecular colloids. Finally, the future directions and challenges for tailoring nanoparticle organization through spatial confinement-mediated entropic effects are detailed. We expect that this review could stimulate further efforts in the fundamental research on the relationship between confinement and entropy and in the applications of this concept for designer nanomaterials.


Assuntos
Nanopartículas , Coloides , Simulação por Computador , Entropia , Nanopartículas/química , Polímeros/química
20.
Animal Model Exp Med ; 5(2): 172-182, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35474613

RESUMO

BACKGROUND: Inflammation is a complex physiological and pathological process. Although many types of inflammation are well characterized, their physiological functions are largely unknown. tRNA aspartic acid methyltransferase 1 (TRDMT1) has been implicated as a stress-related protein, but its intrinsic biological role is unclear. METHODS: We constructed a Trdmt1 knockout rat and adopted the LPS-induced sepsis model. Survival curve, histopathological examination, expression of inflammatory factors, and protein level of TLR4 pathway were analyzed. RESULTS: Trdmt1 deletion had no obvious impact on development and growth. Trdmt1 deletion slightly increased the mortality during aging. Our data showed that Trdmt1 strongly responded in LPS-treated rats, and Trdmt1 knockout rats were vulnerable to LPS treatment with declined survival rate. We also observed more aggravated tissue damage and more cumulative functional cell degeneration in LPS-treated knockout rats compared with control rats. Further studies showed upregulated TNF-α level in liver, spleen, lung, and serum tissues, which may be explained by enhanced p65 and p38 phosphorylation. CONCLUSIONS: Our data demonstrated that Trdmt1 plays a protective role in inflammation by regulating the TLR4-NF-κB/MAPK-TNF-α pathway. This work provides useful information to understand the TRDMT1 function in inflammation.


Assuntos
DNA (Citosina-5-)-Metiltransferases , Sistema de Sinalização das MAP Quinases , NF-kappa B , Receptor 4 Toll-Like , Fator de Necrose Tumoral alfa , Animais , DNA (Citosina-5-)-Metiltransferases/metabolismo , Inflamação , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Ratos , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
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