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1.
Nanomaterials (Basel) ; 11(11)2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34835789

RESUMO

Recently, as a two-dimensional (2D) material, black phosphorous (BP) has attracted more and more attention. However, few efforts have been made to investigate the BP/polyaniline (PANI) nanocomposite for ammonia (NH3) gas sensors. In this work, the BP/PANI nanocomposite as a novel sensing material for NH3 detection, has been synthesized via in situ chemical oxidative polymerization, which is then fabricated onto the interdigitated transducer (IDTs). The electrical properties of the BP/PANI thin film are studied in a large detection range from 1 to 4000 ppm, such as conduction mechanism, response, reproducibility, and selectivity. The experimental result indicates that the BP/PANI sensor shows higher sensitivity and larger detection range than that of PANI. The BP added into PANI, that may enlarge the specific surface area, obtain the special trough structure for gas channels, and form the p-π conjugation system and p-p isotype heterojunctions, which are beneficial to increase the response of BP/PANI to NH3 sensing. Meanwhile, in order to support the discussion result, the structure and morphology of the BP/PANI are respectively measured by Fourier transform infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV-vis), transmission electron microscopy (TEM), and field emissions scanning electron microscopy (SEM). Moreover, the sensor shows good reproducibility, and fast response and recovery behavior, on NH3 sensing. In addition, this route may offer the advantages of an NH3 sensor, which are of simple structure, low cost, easy to assemble, and operate at room temperature.

2.
EBioMedicine ; 73: 103639, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34700283

RESUMO

BACKGROUND: Lung biopsy tissue samples can be used for infection detection and cancer diagnosis. Metagenomic next-generation sequencing (mNGS) has the potential to further improve diagnosis. METHODS: From July 2018 to May 2020, lung biopsy samples of 133 patients with suspected pulmonary infection or abnormal imaging findings were collected and subjected to clinical microbiological testing, Illumina and Nanopore sequencing to identify pathogens. The neural networks were pretrained by extracting features of human reads from 2,095 metagenomic next-generation sequencing results, and the human reads of lung biopsy samples were entered into the validated pipeline to predict the risk of cancer. FINDINGS: Based on the pathogen-cancer detection pipeline, the Illumina platform showed 77·6% sensitivity and 97·6% specificity compared to the composite reference standard for infection diagnosis. However, the Nanopore platform showed 34·7% sensitivity and 98·7% specificity. mNGS identified more fungi, which was confirmed by subsequent pathological examination. M. tuberculosis complex was weakly detected. For cancer detection, compared with histology, the Illumina platform showed 83·7% sensitivity and 97·6% specificity, diagnosing an additional 36 cancer patients, of whom half had abnormal imaging findings (pulmonary shadow, space-occupying lesions, or nodules). INTERPRETATION: For the first time, we have established a pipeline to simultaneously detect pathogens and cancer based on Illumina sequencing of lung biopsy tissue. This pipeline efficiently diagnosed cancer in patients with abnormal imaging findings. FUNDING: This work was supported by the National Key Research and Development Program of China and National Natural Science Foundation of China.

3.
Craniomaxillofac Trauma Reconstr ; 14(3): 231-235, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34471479

RESUMO

Study Design: Retrospective cohort study. Objective: On January 1, 2018, the Strengthen Opioid Misuse Prevention (STOP) Act was implemented to increase oversight over opioid prescriptions in North Carolina. The aim of this study is to evaluate the legislation's efficacy in reducing opioid prescriptions following facial fracture repair. Methods: A retrospective chart review of patients who sustained maxillofacial fractures and underwent repair from January 1, 2015 through December 31, 2019 at a level 1 trauma center was performed. The North Carolina Controlled Substance Database was used to quantify perioperative opioid prescriptions in morphine milligram equivalents (MME). Average MME per patient was compared between 2 groups, patients who underwent surgery before the NC STOP Act came into effect and patients who underwent treatment after. This comparison was also performed on case type subgroups including surgically treated fractures of the orbit, mandible, midface, and multiple regions. A student's t-test was used to compare before and after groups in all analyses. Results: Of the 253 patients who met inclusion criteria, 146 were in the before group, and 107 were in the after group. There was a statistically significant, 30.9% decrease in overall average MME prescribed after the NC STOP Act was enacted. A statistically significant decrease was noted in patients who had facial fractures of multiple regions. Conclusion: Since the implementation of the NC STOP Act in 2018, there have been statistically and clinically significant decreases in the amount of opioids prescribed following surgical management of facial fractures.

4.
Neuroreport ; 32(15): 1248-1254, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34494989

RESUMO

OBJECTIVE: The aim of this study was to investigate the potential therapeutic effects of a newly discovered osteopontin-derived synthetic peptide "RSKKFRR" in a rat model of ischemic stroke. METHODS: A total of 24 male SD rats were randomly divided into three groups. The model of ischemic stroke was made up of the middle cerebral artery occlusion (MACO). The rats were divided into sham operation group (Sham), control group (MACO + PBS) and treatment group (MACO + OPNpt9), eight rats in each group. In the control group and the treatment group, PBS or OPNpt9 was injected into the nasal cavity after MACO once a day, and the area of new blood vessels and the recovery of nerve function were observed 14 days later. Whether the proliferation, migration and tube formation of HUVECs were promoted by OPNpt9 was tested. The expression levels of related proangiogenic factors were also detected. RESULTS: OPNpt9 was found to contribute to cerebral microvascular remodeling and neurological improvement in ischemic rats while promoting endothelial cell migration, proliferation and tube formation in vitro. These effects were mediated by activation of the p-ERK/MMP-9/VEGF pathway. CONCLUSION: In conclusion, OPNpt9 promotes angiogenesis and neurological recovery after ischemic stroke.

5.
Pharmacol Res ; 173: 105834, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34450321

RESUMO

Epigenetic modification is a fundamental biological process in living organisms, which has significant impact on health and behavior. Metabolism refers to a set of life-sustaining chemical reactions, including the uptake of nutrients, the subsequent conversion of nutrients into energy or building blocks for organism growth, and finally the clearance of redundant or toxic substances. It is well established that epigenetic modifications govern the metabolic profile of a cell by modulating the expression of metabolic enzymes. Strikingly, almost all the epigenetic modifications require substrates produced by cellular metabolism, and a large proportion of metabolic enzymes can transfer into nucleus to locally produce substrates for epigenetic modification, thereby providing an alternative link between metabolism, epigenetic modification and gene expression. Here, we summarize the recent literature pertinent to metabolic enzymes functioning as epigenetic modulators in the regulation of chromatin architecture and gene expression.

6.
Front Pharmacol ; 12: 705325, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262463

RESUMO

Patients with Crohn's disease (CD) are inclined to have platelet hyperactivity and an increased risk of intestinal micro-thrombosis. However, the mechanisms underlying platelet hyperactivity in CD are not well understood. We investigated the assembly of platelet NLRP3 inflammasome in patients with active CD and its correlation with platelet hyperactivity. In this study, Real-time PCR and western blotting analyses uncovered that ASC, NLRP3, and active caspase-1 were significantly upregulated in platelets from patients with active CD compared with healthy subjects. As revealed by flow cytometry (FCM) and ELISA analyses, the levels of interleukin-1ß in both serum and isolated platelets were elevated in patients with active CD. Co-immunoprecipitation and immunofluorescence experiments revealed an increased assembly of NLRP3 inflammasome in platelets from patients with active CD. In addition, higher levels of intracellular reactive oxygen species (ROS) were observed in these platelets by FCM. Furthermore, elevated levels of platelet P-selectin exposure and fibrinogen binding were demonstrated in patients with active CD by FCM. They were positively correlated with the protein levels of NLRP3 inflammasome components. Collectively, our results indicate that the ROS-NLRP3 inflammasome-interleukin-1ß axis may contribute to platelet hyperactivity in active CD.

7.
Front Cell Dev Biol ; 9: 691749, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34222259

RESUMO

TNNT2 mutation is associated with a range of cardiac diseases, including dilated cardiomyopathy (DCM). However, the mechanisms underlying the development of DCM and heart failure remain incompletely understood. In the present study, we found the expression of cardiac XIN protein was reduced in TNNT2-ΔK210 hESCs-derived cardiomyocytes and mouse heart tissues. We further investigated whether XIN protects against TNNT2 mutation-induced DCM. Overexpression of the repeat-containing isoform XINB decreased the percentage of myofilaments disorganization and increased cell contractility of TNNT2-ΔK210 cardiomyocytes. Moreover, overexpression of XINB by heart-specific delivery via AAV9 ameliorates DCM remodeling caused by TNNT2-ΔK210 mutation in mice, revealed by partially reversed cardiac dilation, systolic dysfunction and heart fibrosis. These results suggest that deficiency of XIN may play a critical role in the development of DCM. Consequently, our findings may provide a new mechanistic insight and represent a therapeutic target for the treatment of idiopathic DCM.

8.
Inorg Chem ; 60(12): 9192-9198, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34105956

RESUMO

2-Aminoacetophenone (2-AA) is a metabolite produced in large quantities by the pathogenic bacteria Pseudomonas aeruginosa (PA), which is a biomarker for PA in water. State-of-the-art analytical techniques to detect PA usually require expensive instruments and a long analysis time which are not suitable for real-time water quality monitoring, especially for high-quality drinking water. Herein, we reported the application of a europium metal-organic framework (Eu-MOF) as a luminescent sensing material, which provides a facile, environmentally friendly and low-cost way for the fast detection of PA in water. Eu-MOF shows a high sensitivity toward 2-AA with a KSV value of 3.563 × 104 M-1, rapid luminescence response in 12 s and high-selectivity and anti-interference ability with the existence of common detection indexes in drinking water owing to the good match of the energy levels of Eu-MOF and 2-AA. A systematical optimization of the sensing conditions to enhance the sensing function of Eu-MOF for 2-AA was discussed in detail, to give fundamentals for the rational design of MOF-based sensing materials.


Assuntos
Acetofenonas/análise , Európio/química , Estruturas Metalorgânicas/química , Pseudomonas aeruginosa/química , Água/química , Biomarcadores/análise , Estruturas Metalorgânicas/síntese química
9.
Front Mol Biosci ; 8: 683240, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34124163

RESUMO

Background: Hepatocellular carcinoma (HCC) is a tumor with high morbidity and high mortality worldwide. DNA methylation, one of the most common epigenetic changes, might serve a vital regulatory role in cancer. Methods: To identify categories based on DNA methylation data, consensus clustering was employed. The risk signature was yielded by systematic bioinformatics analyses based on the remarkably methylated CpG sites of cluster 1. Kaplan-Meier analysis, variable regression analysis, and ROC curve analysis were further conducted to validate the prognosis predictive ability of risk signature. Gene set enrichment analysis (GSEA) was performed for functional annotation. To uncover the context of tumor immune microenvironment (TIME) of HCC, we employed the ssGSEA algorithm and CIBERSORT method and performed TIMER database exploration and single-cell RNA sequencing analysis. Additionally, quantitative real-time polymerase chain reaction was employed to determine the LRRC41 expression and preliminarily explore the latent role of LRRC41 in prognostic prediction. Finally, mutation data were analyzed by employing the "maftools" package to delineate the tumor mutation burden (TMB). Results: HCC samples were assigned into seven subtypes with different overall survival and methylation levels based on 5'-cytosine-phosphate-guanine-3' (CpG) sites. The risk prognostic signature including two candidate genes (LRRC41 and KIAA1429) exhibited robust prognostic predictive accuracy, which was validated in the external testing cohort. Then, the risk score was significantly correlated with the TIME and immune checkpoint blockade (ICB)-related genes. Besides, a prognostic nomogram based on the risk score and clinical stage presented powerful prognostic ability. Additionally, LRRC41 with prognostic value was corroborated to be closely associated with TIME characterization in both expression and methylation levels. Subsequently, the correlation regulatory network uncovered the potential targets of LRRC41 and KIAA1429. Finally, the methylation level of KIAA1429 was correlated with gene mutation status. Conclusion: In summary, this is the first to identify HCC samples into distinct clusters according to DNA methylation and yield the CpG-based prognostic signature and quantitative nomogram to precisely predict prognosis. And the pivotal player of DNA methylation of genes in the TIME and TMB status was explored, contributing to clinical decision-making and personalized prognosis monitoring of HCC.

10.
Clin Chem ; 67(8): 1133-1143, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34060627

RESUMO

BACKGROUND: Metagenomic next-generation sequencing (mNGS) of plasma cell-free DNA has emerged as a promising diagnostic technology for bloodstream infections. However, a major limitation of current mNGS assays is the high rate of false-positive results due to contamination. METHODS: We made novel use of 3 control groups-external negative controls under long-term surveillance, blood samples with a negative result in conventional tests, and a group of healthy people-that were combined and dedicated to distinguishing contaminants arising from specimen collection, sample processing, and human normal flora. We also proposed novel markers to filter out false-positive interspecies calls. This workflow was applied retrospectively to 209 clinical plasma samples from patients with suspected bloodstream infections. Every pathogen identified by the mNGS test was reviewed to assess the diagnostic performance of the workflow. RESULTS: Our mNGS workflow showed clinical sensitivity of 87.1%, clinical specificity of 80.2%, positive predictive value of 77.9%, and negative predictive value of 88.6% compared with the composite reference standard. Notably, mNGS showed great improvement in clinical specificity compared with the current test while keeping clinical sensitivity at a high level. CONCLUSION: The mNGS workflow with multiple control groups dedicated to distinguishing nonpathogen microbes from real causal pathogens has reducing false-positive results. This contribution, with its optimization of workflow and careful use of controls, can help mNGS become a powerful tool for identifying the pathogens responsible for bloodstream infections.

11.
Cleft Palate Craniofac J ; : 10556656211025191, 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34155920

RESUMO

PURPOSE: The purpose of this study was to evaluate perceived image quality, confidence in identifying key velopharyngeal landmarks, and reliability of making velopharyngeal measures between 3-dimensional (3-D) and 2-D magnetic resonance imaging (MRI) methods and between T1-, T2-, and proton density (PD)-weighted sequences. METHODS: Twelve healthy participants completed an MRI study. Three raters assessed overall image quality and their ability to identify key anatomic features within the images. A single rater evaluated the reliability of making measures between imaging methods and sequence types to determine if image type (2-D and 3-D) or image sequence (T1, T2, PD weighted) resulted in different values for key velopharyngeal landmarks. RESULTS: An analysis of variance test revealed image quality was rated significantly different based on the scan type (P < .001) and the sequence used (P = .015). Image quality was rated higher among 2-D MR images compared to 3-D, and higher among T2 sequences compared to T1- and PD-weighted imaging methods. In contrast, raters favored 3-D sequences over 2-D sequences for identifying velopharyngeal landmarks. Measures of reliability revealed scan type significantly impacted 2 of the 6 variables but to a minimal degree; however, sequence type had no impact on measures of reliability across all variables. CONCLUSION: Results of the study suggest the scan type and sequence used are factors that likely do not impact the reliability of measures. Based on image quality, the recommended technique for velopharyngeal imaging would be using a 2-D T2-weighted technique. However, based on the ability to identify key landmarks, a 3-D T1- or PD-weighted technique was favored.

12.
J Magn Reson Imaging ; 54(6): 1754-1760, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34117662

RESUMO

BACKGROUND: Bone marrow of patients with aplastic anemia (AA) is different from that of patients with myelodysplastic syndrome (MDS) and is difficult to identify by blood examination. IDEAL-IQ (iterative decomposition of water and fat with echo asymmetry and least-squares estimation) imaging might be able to quantify fat fraction (FF) and iron content in bone tissues. PURPOSE: To determine if IDEAL-IQ measurements of bone marrow FF and iron content can distinguish between patients with AA and MDS. STUDY TYPE: Retrospective. POPULATION: Fifty-seven patients with AA, 21 patients with MDS, and 24 healthy controls. FIELD STRENGTH/SEQUENCE: 3.0 T, IDEAL-IQ sequence. ASSESSMENT: Three independent observers evaluated the IDEAL-IQ images and measured FF and R2* in the left posterior superior iliac spine. STATISTICAL TESTS: Kruskal-Wallis test, linear correlations, and Bland-Altman analysis were used. A P-value of <0.05 was considered statistically significant. RESULTS: The FF in patients with AA (79.46% ± 15.00%) was significantly higher than that in patients with MDS (42.78% ± 30.09%) and control subjects (65.50% ± 14.73%). However, there was no significant difference in FF between control subjects and patients with MDS (P = 0.439). The R2* value of AA, MDS, and controls was 145.38 ± 53.33, (171.13 ± 100.89, and 135.99 ± 32.41/second, respectively, with no significant difference between the three groups (P = 0.553). DATA CONCLUSION: Quantitative IDEAL-IQ magnetic resonance imaging may facilitate the diagnosis of AA and distinguish it from MDS. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

13.
BMC Endocr Disord ; 21(1): 97, 2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-33964922

RESUMO

AIMS: Hyperuricemia has attracted increasing attention. However, limited concern has been paid to the potential dangers of lowering serum uric acid (SUA). We observed lower levels of SUA in patients with COVID-19. Therefore, we aim to explore whether patients with COVID-19 had SUA lower than normal and the relationship of SUA and the severity of COVID-19. METHODS: This was a case-control study based on 91 cases with COVID-19 and 273 age- and sex-matched healthy control subjects. We first compared SUA levels and uric acid/creatinine (UA/Cr) ratio between patients with COVID-19 and the healthy controls. Then, we examined the association of SUA levels and UA/Cr ratios with COVID-19 severity in COVID-19 cases only, defined according to the fifth edition of China's Diagnosis and Treatment Guidelines of COVID-19. RESULTS: SUA levels in patients with COVID-19 were 2.59% lower, UA/Cr ratios 6.06% lower at admission compared with healthy controls. In sex stratified analysis, levels of SUA and UA/Cr were lower in male patients with COVID-19 while only level of SUA was lower in female patients with COVID-19. Moreover, SUA and UA/Cr values were 4.27 and 8.23% lower in the severe group than that in the moderate group among male COVID-19 patients. Bivariate and partial correlations analysis showed negative correlations between SUA or UA/Cr ratio and COVID-19 after adjusting for age, sex, BMI and eGFR. A multiple linear regression analysis showed that SARS-CoV-2 infection and male sex were independent risk factors associated with lower SUA levels. Male patients with COVID-19 accompanied by low SUA levels had higher risk of developing severe symptoms than those with high SUA levels (incidence rate ratio: 4.05; 95% CI:1.11, 14.72) at admission. Comparing SUA and UA/Cr ratio at three time points (admission, discharge, and follow-up), we found that male patients experienced severe symptoms had lower SUA and UA/Cr ratio levels comparing to moderate patients, but no significant difference between three time points. On the contrary, female patients had lower SUA and UA/Cr ratio at discharge than those at admission, but no significant difference of SUA and UA/Cr ratio between moderate and severe group. CONCLUSION: Patients with COVID-19 had SUA and UA/Cr values lower than normal at admission. Male COVID-19 patients with low SUA levels had a significantly higher crude risk of developing severe symptoms than those with high SUA levels. During disease aggravation, the level of SUA gradually decreased until discharge. At the follow-up exam, the level of SUA was similar to the levels at admission.


Assuntos
COVID-19/sangue , SARS-CoV-2 , Ácido Úrico/sangue , Adulto , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais
15.
Thromb J ; 19(1): 27, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910580

RESUMO

BACKGROUND: Sphingomyelin (SM) is an essential component of biological lipid rafts, and it plays an indispensable role in maintaining plasma membrane stability and in mediating signal transduction. The ultimate biosynthesis of SM is catalyzed by two sphingomyelin synthases (SMSs) namely SMS1 and SMS2, which are selectively distributed in the trans-Golgi apparatus and the plasma membrane. It has been demonstrated that SMS2 acts as an irreplaceable molecule in the regulation of transmembrane signaling, and loss of SMS2 has been reported to worsen atherosclerosis and liver steatosis. However, the function of SMS2 in platelet activation and its association with the pathological process of thrombosis in acute coronary syndrome (ACS) and portal hypertension (PH) remain unclear. METHODS: In this study, we tested the role of SMS2 in platelet activation and thrombosis using SMS2 knockout (SMS2 -/-) mice and SMS2-specific inhibitor, D609. Furthermore, we detected SMS2 expression in patients with ACS and PH. RESULTS: SMS2 -/- platelets showed significant reduction in platelet aggregation, spreading, clot retraction and in vivo thrombosis. Similar inhibitory effects on platelet activation were detected in D609-treated wild-type platelets. PLCγ/PI3K/Akt signaling pathway was inhibited in SMS2 -/- platelets and D609-treated wild-type platelets. In addition, we discovered that platelet SMS2 expression was remarkably increased in patients with ACS and PH, compared with healthy subjects. CONCLUSIONS: Our study indicates that SMS2 acts as a positive regulator of platelet activation and thrombosis, and provides a theoretical basis for the potential use of D609 in anti-thrombosis treatment.

16.
Eur Radiol ; 31(9): 7067-7076, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33755755

RESUMO

OBJECTIVE: To develop a non-contrast CT-based radiomic signature to effectively screen for thoracic aortic dissections (ADs). METHODS: We retrospectively enrolled 378 patients who underwent non-contrast chest CT scans along with CT angiography or MRI from 4 medical centers. The training and validation sets were from 3 centers, while the external test set was from a 4th center. Radiomic features were extracted from non-contrast CT images. The radiomic signature was created on the basis of selected features by a logistic regression algorithm. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve, accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were conducted to assess the predictive ability of radiomic signature. RESULTS: The radiomic signature demonstrated AUCs of 0.91 (95% confidence interval [CI], 0.86-0.95) in the training set, 0.92 (95% CI, 0.86-0.98) in the validation set, and 0.90 (95% CI, 0.82-0.98) in the external test set. The predicted diagnosis was in good agreement with the probability of thoracic AD. In the external test group, the diagnostic accuracy, sensitivity, specificity, PPV, and NPV were 90.5%, 85.7%, 91.7%, 70.6%, and 96.5%, respectively. CONCLUSIONS: A radiomic signature based on non-contrast CT images can effectively predict thoracic ADs. This method may serve as a potential screening tool for thoracic ADs. KEY POINTS: • The non-contrast CT-based radiomic signature can effectively predict the thoracic aortic dissections. • This radiomic signature shows better predictive performance compared to the current clinical model. • This prediction method may be a potential tool for screening thoracic aortic dissections.


Assuntos
Aneurisma Dissecante , Tomografia Computadorizada por Raios X , Aneurisma Dissecante/diagnóstico por imagem , Área Sob a Curva , Humanos , Curva ROC , Estudos Retrospectivos
17.
Theranostics ; 11(7): 3348-3358, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33537091

RESUMO

Pin1 belongs to the peptidyl-prolyl cis-trans isomerases (PPIases) superfamily and catalyzes the cis-trans conversion of proline in target substrates to modulate diverse cellular functions including cell cycle progression, cell motility, and apoptosis. Dysregulation of Pin1 has wide-ranging influences on the fate of cells; therefore, it is closely related to the occurrence and development of various diseases. This review summarizes the current knowledge of Pin1 in disease pathogenesis.


Assuntos
Doenças Cardiovasculares/genética , Diabetes Mellitus Tipo 2/genética , Peptidilprolil Isomerase de Interação com NIMA/genética , Neoplasias/genética , Neovascularização Patológica/genética , Doenças Neurodegenerativas/genética , Obesidade/genética , Viroses/genética , Apoptose/genética , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Ciclo Celular/genética , Movimento Celular , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Regulação da Expressão Gênica , Humanos , Peptidilprolil Isomerase de Interação com NIMA/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Obesidade/metabolismo , Obesidade/patologia , Transdução de Sinais , Viroses/metabolismo , Viroses/patologia
18.
Am J Cancer Res ; 11(2): 370-388, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33575077

RESUMO

Glioma is currently the most widespread and malignant primary intracranial tumor, which is characterized by high heterogeneity and high fatality rates. ß-elemene, which is a bioactive compound extracted from a Chinese herb, Curcuma wenyujin, has been reported to reduce resistance of chemotherapeutic drugs and induce apoptosis in tumor cells. However, the role and mechanisms of ß-elemene in glioma senescence remains unknown. In the present study, we found that a low concentration of ß-elemene (10 µg/mL) induced senescence in glioma cells, including reduction of cell proliferation, hypertrophic morphology, increase of senescence-associated ß-galactosidase (SA-ß-Gal) activity, upregulation of several senescence-associated genes such as p16, p53 and NF-κB, and downregulation of Lamin B1. However, a high concentration of ß-elemene induced apoptosis in glioma cells. Treatment with ß-elemene caused a marked down-regulation of Yes-associated protein (YAP) expression in glioma cells, which is a key transcriptional co-activator in multiple cancers. Moreover, cyclin dependent kinase 6 (CDK6), which is a known downstream target of YAP, was decreased in glioma cells that treated with ß-elemene. The overexpression of YAP and CDK6 significantly rescued ß-elemene-induced senescence in glioma cells. Finally, ß-elemene treatment also induced the senescence of glioma cells in glioma xenograft model through inactivation of YAP-CDK6 pathways, which might inhibit the glioma growth. Taken together, these results reveal a previously unknown role of ß-elemene in glioma cell senescence in vitro and in vivo that is associated with YAP-CDK6 signaling pathway, which will enhance our understanding of glioma cell senescence, and provide novel strategies for the treatment of gliomas.

19.
J Cell Physiol ; 236(6): 4152-4173, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33452680

RESUMO

Autophagy is an evolutionarily conserved intracellular process and is considered one of the main catabolism pathways. In the process of autophagy, cells are digested nonselectively or selectively to recover nutrients and energy, so it is regarded as an antiaging process. In addition to the essential role of autophagy in cellular homeostasis, autophagy is a stress response mechanism for cell survival. Here, we review recent literature describing the pathway of autophagy and its role in different bone cell types, including osteoblasts, osteoclasts, and osteocytes. Also discussed is the mechanism of autophagy in bone diseases associated with bone homeostasis, including osteoporosis and Paget's disease. Finally, we discuss the application of autophagy regulators in bone diseases. This review aims to introduce autophagy, summarize the understanding of its relevance in bone physiology, and discuss its role and therapeutic potential in the pathogenesis of bone diseases such as osteoporosis.


Assuntos
Autofagia , Remodelação Óssea , Osso e Ossos/patologia , Osteíte Deformante/patologia , Osteoartrite/patologia , Osteoporose/patologia , Animais , Autofagia/efeitos dos fármacos , Proteínas Relacionadas à Autofagia/metabolismo , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Osso e Ossos/fisiopatologia , Homeostase , Humanos , Osteíte Deformante/tratamento farmacológico , Osteíte Deformante/metabolismo , Osteíte Deformante/fisiopatologia , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Osteoartrite/fisiopatologia , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Osteoporose/fisiopatologia
20.
Hand (N Y) ; : 1558944720975139, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33410716

RESUMO

There have been 8 synovial sarcomas of the median nerve reported. We report a case of a 15-year-old male with synovial sarcoma of the right-hand median nerve. Patient presented with a 2-month history of enlarging mass at the base of the right thenar eminence associated with numbness in the median nerve distribution. Physical examination revealed a soft mass over the thenar eminence and paresthesia in the median nerve distribution. He underwent excision of the tumor, which revealed a well-encapsulated lesion encompassing the median nerve, involving the first, second, and radial aspect of the third web space as well as recurrent branches of the median nerve. Following excision of the tumor, a thorough metastatic workup was negative for metastatic disease. He was staged as III, T2b, N0, M0-poorly differentiated monophasic synovial sarcoma of the right median nerve. Postoperatively the patient was started on chemotherapy and radiation. Intraneural synovial sarcoma is extremely rare. Our case is the youngest with the longest follow-up. He is currently at a status of 3 years posttreatment with no signs of recurrence and excellent use of his right hand. This case is of particular interest due to the rarity of the disease along with this being the best outcome reported in the literature to-date.

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