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1.
Eur J Neurosci ; 60(8): 5831-5848, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39233436

RESUMO

Previous studies have suggested that the morphology and function of the thalamus and cortex are abnormal in patients with knee osteoarthritis (KOA). However, whether the thalamocortical network is differentially affected in this disorder is unknown. In this study, we examined functional and effective connectivity between the thalamus and major divisions of the cortex in 27 healthy controls and 27 KOA patients using functional magnetic resonance imaging. We also explored the topological features of the brain via graph theory analysis. The results suggested that patients with KOA had significantly reduced resting-state functional connectivity (rsFC) of the thalamo-sensorimotor pathway; enhanced rsFC of the thalamo-medial/lateral frontal cortex (mFC/LFC), parietal, temporal and occipital pathways; reduced effective connectivity of the left sensorimotor-to-thalamus pathway; and enhanced effective connectivity of the right thalamus-to-sensorimotor pathway compared with healthy controls. The functional connectivity of the thalamo-sensorimotor and thalamo-mFC pathways was enhanced when patients performed the multisource interference task. Moreover, patients with KOA presented altered nodal properties associated with thalamocortical circuits, including the thalamus, amygdala, and regions in default mode networks, compared with healthy controls. The correlation analysis suggested a significant negative correlation between thalamo-mFC rsFC and pain intensity, between thalamo-sensorimotor task-related connectivity and disease duration/depression scores, and a positive correlation between right frontal nodal properties and pain intensity in KOA patients. Taken together, these findings establish abnormal and differential alterations in the thalamocortical network associated with pain characteristics in KOA patients, which extends our understanding of their role in the pathophysiology of KOA.


Assuntos
Córtex Cerebral , Imageamento por Ressonância Magnética , Osteoartrite do Joelho , Tálamo , Humanos , Feminino , Masculino , Osteoartrite do Joelho/fisiopatologia , Osteoartrite do Joelho/diagnóstico por imagem , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Tálamo/fisiopatologia , Tálamo/diagnóstico por imagem , Idoso , Córtex Cerebral/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Conectoma/métodos , Rede Nervosa/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Dor/fisiopatologia , Dor/diagnóstico por imagem , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem
2.
Anal Chem ; 96(40): 16099-16108, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39319639

RESUMO

As digital data undergo explosive growth, deoxyribonucleic acid (DNA) has emerged as a promising storage medium due to its high density, longevity, and ease of replication, offering vast potential in data storage solutions. This study focuses on the protection and retrieval of data during the DNA storage process, developing a technique that employs flow cytometry sorting (FCS) to segregate multicolored fluorescent DNA microparticles encoded with data and facilitating efficient random access. Moreover, the encapsulated fluorescent DNA microparticles, formed through layer-by-layer self-assembly, preserve structural and sequence integrity even under harsh conditions while also supporting a high-density DNA payload. Experimental results have shown that the encoded data can still be successfully recovered from encapsulated DNA microparticles following de-encapsulation. We also successfully demonstrated the automated encapsulation process of fluorescent DNA microparticles using a microfluidic chip. This research provides an innovative approach to the long-term stability and random readability of DNA data storage.


Assuntos
DNA , Citometria de Fluxo , DNA/química , Corantes Fluorescentes/química , Armazenamento e Recuperação da Informação
3.
Nano Lett ; 23(19): 9056-9064, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37738391

RESUMO

Sepsis is an acute systemic infectious syndrome with high fatality. Fast and accurate diagnosis, monitoring, and medication of sepsis are essential. We exploited the fluorescent metal-AIEgen frameworks (MAFs) and demonstrated the dual functions of protein detection and bacteria identification: (i) ultrasensitive point-of-care (POC) detection of sepsis biomarkers (100 times enhanced sensitivity); (ii) rapid POC identification of Gram-negative/positive bacteria (selective aggregation within 20 min). Fluorescent lateral flow immunoassays (LFAs) are convenient and inexpensive for POC tests. MAFs possess a large surface area, excellent photostability, high quantum yield (∼80%), and multiple active sites serving as protein binding domains for ultrasensitive detection of sepsis biomarkers (IL-6/PCT) on LFAs. The limit of detection (LOD) for IL-6/PCT is 0.252/0.333 pg/mL. Rapid appraisal of infectious bacteria is vital to guide the use of medicines. The dual-functional fluorescent MAFs have great potential in POC tests for the clinical diagnosis of bacterial infections.

4.
Anal Chem ; 95(6): 3423-3433, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36735936

RESUMO

Correlated analysis of multiple biochemical parameters at the single-particle level and in a high-throughput manner is essential for insights into the diversity and functions of biological nanoparticles (BNPs), such as bacteria and subcellular organelles. To meet this challenge, we developed a highly sensitive spectral nano-flow cytometer (S-nFCM) by integrating a spectral recording module to a laboratory-built nFCM that is 4-6 orders of magnitude more sensitive in side scattering detection and 1-2 orders of magnitude more sensitive in fluorescence detection than conventional flow cytometers. An electron-multiplying charge-coupled device (EMCCD) was used to acquire the full fluorescence spectra of single BNPs upon holographic grating dispersion. Up to 10,000 spectra can be collected in 1 min with 2.1 nm resolution. The precision, linearity, and sensitivity were examined. Complete discernment of single influenza viruses against the background signal, discrimination of different strains of marine cyanobacteria in a mixed sample based on their spectral properties of natural fluorescence, classification of bacterial categories exhibiting different patterns of antigen expression, and multiparameter analysis of single mitochondria for drug discovery were successfully demonstrated.


Assuntos
Nanopartículas , Mitocôndrias , Organelas
5.
Eur Radiol ; 33(5): 3332-3342, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36576544

RESUMO

OBJECTIVES: To determine whether radiomics features derived from diffusion-weighted imaging (DWI) and arterial spin labeling (ASL) can improve the differentiation between radiation-induced brain injury (RIBI) and tumor recurrence (TR) in glioma patients. METHODS: A total of 4199 radiomics features were extracted from conventional MRI, apparent diffusion coefficient (ADC), and cerebral blood flow (CBF) maps, obtained from 96 pathologically confirmed WHO grade 2~4 gliomas with enhancement after standard treatment. The intraclass correlation coefficient (ICC) was used to test segmentation stability between two doctors. Radiomics features were selected using the Mann-Whitney U test, LASSO regression, and RFE algorithms. Four machine learning classifiers were adopted to establish radiomics models. The diagnostic performance of multiparameter, conventional, and single-parameter MRI radiomics models was compared using the area under the curve (AUC). The models were evaluated in the subsequent independent validation set (n = 30). RESULTS: Eight important radiomics features (3 from conventional MRI, 1 from ADC, and 4 from CBF) were selected. Support vector machine (SVM) was chosen as the optimal classifier. The diagnostic performance of the multiparameter MRI radiomics model (AUC 0.96) was higher than that of the conventional MRI (AUC 0.88), ADC (AUC 0.91), and CBF (AUC 0.95) radiomics models. For subgroup analysis, the multiparameter MRI radiomics model showed similar performance, with AUCs of 0.98 in WHO grade 2~3 and 0.96 in WHO grade 4. CONCLUSION: The incorporation of noninvasive DWI and ASL into the MRI radiomics model improved the diagnostic performance in differentiating RIBI from TR; ASL, especially, played a significant role. KEY POINTS: • The multiparameter MRI radiomics model was superior to the conventional MRI radiomics model in differentiating glioma recurrence from radiation-induced brain injury. • Diffusion and perfusion MRI could improve the ability of the radiomics model in predicting the progression in patients with glioma. • Arterial spin labeling played an important role in predicting glioma progression using radiomics models.


Assuntos
Lesões Encefálicas , Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patologia , Marcadores de Spin , Recidiva Local de Neoplasia/diagnóstico por imagem , Glioma/diagnóstico por imagem , Glioma/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética , Estudos Retrospectivos
6.
Anal Chem ; 94(38): 13153-13162, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-36106626

RESUMO

Biopolymers are considered a promising alternative for information storage, and the most successful implementation has been using chemically synthesized DNA to represent binary data, which has achieved tremendous progress at multiple fronts bridging biotechnology with digital information. Currently, a majority of these systems are lacking the system integration and process automation expected by users of digital data and overly use tubes/vials for DNA storage. Herein, we present a microfluidic platform for automated storage and retrieval of data-encoding oligonucleotide samples enabled by a microvalve network architecture. Our platform, equipped with individually addressable compartments, offers an orthogonal strategy of data partitioning and file indexing with respect to the molecular-based random access implementation, with each partition amounting to an equivalence of 9.5 TB data within a 4 × 2 mm2 area. We examined the functionality of the presented platform and its compatibility with the DNA storage workflow coupled with nanopore sequencing to fully recover the stored files, demonstrating a significantly enhanced degree of function integration and process automation compared to that of the existing microfluidic approach.


Assuntos
DNA , Microfluídica , DNA/genética , Oligonucleotídeos , Análise de Sequência de DNA , Manejo de Espécimes
7.
J Cell Mol Med ; 19(9): 2215-31, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26119034

RESUMO

Promotion of myofibroblast apoptosis is a potential therapeutic strategy for pulmonary fibrosis. This study investigated the antifibrotic effect of astaxanthin on the promotion of myofibroblast apoptosis based on dynamin-related protein-1 (Drp1)-mediated mitochondrial fission in vivo and in vitro. Results showed that astaxanthin can inhibit lung parenchymal distortion and collagen deposition, as well as promote myofibroblast apoptosis. Astaxanthin demonstrated pro-apoptotic function in myofibroblasts by contributing to mitochondrial fission, thereby leading to apoptosis by increasing the Drp1 expression and enhancing Drp1 translocation into the mitochondria. Two specific siRNAs were used to demonstrate that Drp1 is necessary to promote astaxanthin-induced mitochondrial fission and apoptosis in myofibroblasts. Drp1-associated genes, such as Bcl-2-associated X protein, cytochrome c, tumour suppressor gene p53 and p53-up-regulated modulator of apoptosis, were highly up-regulated in the astaxanthin group compared with those in the sham group. This study revealed that astaxanthin can prevent pulmonary fibrosis by promoting myofibroblast apoptosis through a Drp1-dependent molecular pathway. Furthermore, astaxanthin provides a potential therapeutic value in pulmonary fibrosis treatment.


Assuntos
Apoptose/efeitos dos fármacos , GTP Fosfo-Hidrolases/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Dinâmica Mitocondrial , Proteínas Mitocondriais/metabolismo , Miofibroblastos/patologia , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/prevenção & controle , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Contagem de Células , Linhagem Celular Tumoral , Modelos Animais de Doenças , Dinaminas , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Dinâmica Mitocondrial/efeitos dos fármacos , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/ultraestrutura , Transporte Proteico/efeitos dos fármacos , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Fibrose Pulmonar/patologia , Ratos Sprague-Dawley , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Xantofilas/farmacologia , Xantofilas/uso terapêutico , Proteína X Associada a bcl-2/metabolismo
8.
J Cell Mol Med ; 18(11): 2198-212, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25215580

RESUMO

Oxidative stress is an important molecular mechanism underlying lung fibrosis. The mitochondrion is a major organelle for oxidative stress in cells. Therefore, blocking the mitochondrial signalling pathway may be the best therapeutic manoeuver to ameliorate lung fibrosis. Astaxanthin (AST) is an excellent antioxidant, but no study has addressed the pathway of AST against pulmonary oxidative stress and free radicals by the mitochondrion-mediated signalling pathway. In this study, we investigated the antioxidative effects of AST against H2 O2 - or bleomycin (BLM)-induced mitochondrial dysfunction and reactive oxygen species (ROS) production in alveolar epithelial cells type II (AECs-II) in vivo and in vitro. Our data show that AST blocks H2 O2 - or BLM-induced ROS generation and dose-dependent apoptosis in AECs-II, as characterized by changes in cell and mitochondria morphology, translocation of apoptotic proteins, inhibition of cytochrome c (Cyt c) release, and the activation of caspase-9, caspase-3, Nrf-2 and other cytoprotective genes. These data suggest that AST inhibits apoptosis in AECs-II cells through the ROS-dependent mitochondrial signalling pathway and may be of potential therapeutic value in lung fibrosis treatment.


Assuntos
Apoptose/efeitos dos fármacos , Fibrose/tratamento farmacológico , Estresse Oxidativo , Antioxidantes/administração & dosagem , Linhagem Celular , Citocromos c/biossíntese , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Fibrose/patologia , Radicais Livres , Humanos , Mitocôndrias/efeitos dos fármacos , Alvéolos Pulmonares/efeitos dos fármacos , Alvéolos Pulmonares/patologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Xantofilas/administração & dosagem
9.
J Cell Mol Med ; 18(12): 2404-16, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25284615

RESUMO

Apoptosis of type II alveolar epithelial cells (AECs-II) is a key determinant of initiation and progression of lung fibrosis. However, the mechanism of miR-30a participation in the regulation of AECs-II apoptosis is ambiguous. In this study, we investigated whether miR-30a could block AECs-II apoptosis by repressing mitochondrial fission dependent on dynamin-related protein-1 (Drp-1). The levels of miR-30a in vivo and in vitro were determined through quantitative real-time PCR (qRT-PCR). The inhibition of miR-30a in AECs-II apoptosis, mitochondrial fission and its dependence on Drp-1, and Drp-1 expression and translocation were detected using miR-30a mimic, inhibitor-transfection method (gain- and loss-of-function), or Drp-1 siRNA technology. Results showed that miR-30a decreased in lung fibrosis. Gain- and loss-of-function studies revealed that the up-regulation of miR-30a could decrease AECs-II apoptosis, inhibit mitochondrial fission, and reduce Drp-1 expression and translocation. MiR-30a mimic/inhibitor and Drp-1 siRNA co-transfection showed that miR-30a could inhibit the mitochondrial fission dependent on Drp-1. This study demonstrated that miR-30a inhibited AECs-II apoptosis by repressing the mitochondrial fission dependent on Drp-1, and could function as a novel therapeutic target for lung fibrosis.


Assuntos
Apoptose/genética , Células Epiteliais/metabolismo , GTP Fosfo-Hidrolases/genética , MicroRNAs/genética , Proteínas Associadas aos Microtúbulos/genética , Dinâmica Mitocondrial/genética , Proteínas Mitocondriais/genética , Animais , Linhagem Celular Tumoral , Células Cultivadas , Dinaminas , GTP Fosfo-Hidrolases/metabolismo , Humanos , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Proteínas Associadas aos Microtúbulos/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Proteínas Mitocondriais/metabolismo , Alvéolos Pulmonares/citologia , Fibrose Pulmonar/genética , Fibrose Pulmonar/metabolismo , Interferência de RNA , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa
10.
BMC Pulm Med ; 14: 67, 2014 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-24755111

RESUMO

BACKGROUND: Acute interstitial pneumonia is a rare interstitial lung disease that rapidly progresses to respiratory failure or death. Several studies showed that myofibroblast plays an important role in the evolution of diffuse alveolar damage, which is the typical feature of acute interstitial pneumonia. However, no evidence exists whether alveolar epithelial cells are an additional source of myofibroblasts via epithelial-mesenchymal transition in acute interstitial pneumonia. CASE PRESENTATION: In this report, we present a case of acute interstitial pneumonia in a previously healthy 28-year-old non-smoking woman. Chest high-resolution computed tomography scan showed bilateral and diffusely ground-glass opacification. The biopsy was performed on the fifth day of her hospitalization, and results showed manifestation of acute exudative phase of diffuse alveolar damage characterized by hyaline membrane formation. On the basis of the preliminary diagnosis of acute interstitial pneumonia, high-dose glucocorticoid was used. However, this drug showed poor clinical response and could improve the patient's symptoms only during the early phase. The patient eventually died of respiratory dysfunction. Histological findings in autopsy were consistent with the late form of acute interstitial pneumonia. CONCLUSIONS: The results in this study revealed that alveolar epithelial cells underwent epithelial-mesenchymal transition and may be an important origin of myofibroblasts in the progression of acute interstitial pneumonia. Conducting research on the transformation of alveolar epithelial cells into myofibroblasts in the lung tissue of patients with acute interstitial pneumonia may be beneficial for the treatment of this disease. However, to our knowledge, no research has been conducted on this topic.


Assuntos
Transição Epitelial-Mesenquimal/fisiologia , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/patologia , Insuficiência Respiratória/fisiopatologia , Tomografia Computadorizada por Raios X/métodos , Doença Aguda , Adulto , Biópsia por Agulha , Progressão da Doença , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Evolução Fatal , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imuno-Histoquímica , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Raras , Medição de Risco , Índice de Gravidade de Doença
11.
Artigo em Inglês | MEDLINE | ID: mdl-38861438

RESUMO

Early diagnosis of Alzheimer's disease (AD) is crucial for its prevention, and hippocampal atrophy is a significant lesion for early diagnosis. The current DL-based AD diagnosis methods only focus on either AD classification or hippocampus segmentation independently, neglecting the correlation between the two tasks and lacking pathological interpretability. To address this issue, we propose a Reliable Hippo-guided Learning model for Alzheimer's Disease diagnosis (RLAD), which employs multi-task learning for AD classification as a main task supplemented by hippocampus segmentation. More specifically, our model consists of 1) a hybrid shared features encoder that encodes local and global information in MRI to enhance the model's ability to learn discriminative features; 2) Task Specific Decoders to accomplish AD classification and hippocampus segmentation; and 3) Task Coordination module to correlate the two tasks and guide the classification task to focus on the hippocampus area. Our proposed RLAD model is evaluated on MRI scans of 1631 subjects from three independent datasets, including ADNI-1, ADNI-2, and HarP. Our extensive experimental results demonstrate that the proposed model significantly improves the performance of AD classification and hippocampus segmentation with strong generalization capabilities. Our implementation and model are available at https://github.com/LeoLjl/Explainable-Alzheimer-s-Disease-Diagnosis.

12.
J Pain Res ; 17: 2133-2146, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915479

RESUMO

Purpose: Chronic low back pain (cLBP) is a recurring and intractable disease that is often accompanied by emotional and cognitive disorders such as depression and anxiety. The nucleus accumbens (NAc) plays an important role in mediating emotional and cognitive processes and analgesia. This study investigated the resting-state functional connectivity (rsFC) and effective connectivity (EC) of NAc and its subregions in cLBP. Methods: Thirty-four cLBP patients and 34 age- and sex-matched healthy controls (HC) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Seed-based rsFC and Dynamic Causal Modelling (DCM) were used to examine the alteration of the rsFC and EC of the NAc. Results: Our results showed that the cLBP group had increased rsFC of the bilateral NAc-left superior frontal cortex (SFC), orbital frontal cortex (OFC), left angular gyrus, the left NAc-bilateral middle temporal gyrus, as well as decreased rsFC of left NAc-left supramarginal gyrus, right precentral gyrus, left cerebellum, brainstem (medulla oblongata), and right insula pathways compared with the HC; the results of the subregions were largely consistent with the whole NAc. In addition, the rsFC of the left NAc-left SFC was negatively correlated with Hamilton's Depression Scale (HAMD) scores (r = -0.402, p = 0.018), and the rsFC of left NAc-OFC was positively correlated with present pain intensity scores (r = 0.406, p = 0.017) in the cLBP group. DCM showed that the cLBP group showed significantly increased EC from the left cerebellum to the right NAc (p = 0.012) as compared with HC. Conclusion: Overall, our findings demonstrate aberrant rsFC and EC between NAc and regions that are associated with emotional regulation and cognitive processing in individuals with cLBP, underscoring the pivotal roles of emotion and cognition in cLBP.

13.
Cardiooncology ; 10(1): 56, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39232830

RESUMO

BACKGROUND: Cardiovascular toxicity represents a significant adverse consequence of cancer therapies, yet there remains a paucity of effective biomarkers for its timely monitoring and diagnosis. To give a first evidence able to elucidate the role of Growth Differentiation Factor 15 (GDF15) in the context of cancer diagnosis and its specific association with cardiac indicators in cancer patients, thereby testing its potential in predicting the risk of CTRCD (cancer therapy related cardiac dysfunction). METHODS: Analysis of differentially expressed genes (DEGs), including GDF15, was performed by utilizing data from the public repositories of the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Cardiomyopathy is the most common heart disease and its main clinical manifestations, such as heart failure and arrhythmia, are similar to those of CTRCD. Examination of GDF15 expression was conducted in various normal and cancerous tissues or sera, using available database and serum samples. The study further explored the correlation between GDF15 expression and the combined detection of cardiac troponin-T (c-TnT) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP), assessing the combined diagnostic utility of these markers in predicting risk of CTRCD through longitudinal electrocardiograms (ECG). RESULTS: GDF15 emerged as a significant DEG in both cancer and cardiomyopathy disease models, demonstrating good diagnostic efficacy across multiple cancer types compared to healthy controls. GDF15 levels in cancer patients correlated with the established cardiac biomarkers c-TnT and NT-proBNP. Moreover, higher GDF15 levels correlated with an increased risk of ECG changes in the cancer cohort. CONCLUSION: GDF15 demonstrated promising diagnostic potential in cancer identification; higher GDF15, combined with elevated cardiac markers, may play a role in the monitoring and prediction of CTRCD risk.

14.
Lab Invest ; 93(11): 1219-31, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24042439

RESUMO

The transforming growth factor-ß1 (TGF-ß1)/Smad3 signaling pathway has a central role in pathogenesis of lung fibrosis. In the present study, we investigated if all-trans retinoic acid (ATRA) could attenuate fibrosis in bleomycin (BLM)-induced lung fibrosis in rats through regulating TGF-ß1/Smad3 signaling. Beginning on day 14 after BLM administration, the ATRA I and II groups of rats received daily oral administration of ATRA for 14 days. All rats were killed on day 28. Lung tissue sections were prepared and subject to histological assessment, and expression levels of proteins involved in the TGF-ß1 signaling cascade and epithelial-mesenchymal transition (EMT) were evaluated by transmission electron microscopy (TEM), quantitative real-time polymerase chain reaction (qRT-PCR), western blot procedure, and immunohistochemical or immunofluorescence staining. BLM significantly increased the alveolar septum infiltrates, inflammatory cell infiltrates, and collagen fibers. These BLM-induced changes were significantly ameliorated by ATRA treatment. In addition, BLM significantly increased levels of lung fibrosis markers α-SMA, hydroxyproline (Hyp), collagen I, Snail, and Twist, whereas significantly decreased E-cadherin expression. ATRA treatment largely reversed BLM-induced changes in these lung fibrosis markers. ATRA also blocked BLM-induced activation of the TGF-ß1/Smad3 signaling pathway in lung tissues, including expression of TGF-ß1, Smad3, p-Smad3, zinc-finger E-box-binding homeobox 1 and 2 (ZEB1 and ZEB2), and the high-mobility group AT-hook 2 (HMGA2). Our results suggest that ATRA may have potential therapeutic value for lung fibrosis treatment.


Assuntos
Bleomicina/antagonistas & inibidores , Bleomicina/toxicidade , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Tretinoína/farmacologia , Animais , Biomarcadores/metabolismo , Colágeno/metabolismo , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Proteína HMGA2/genética , Proteína HMGA2/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Fibrose Pulmonar/induzido quimicamente , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Proteína Smad3/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fator de Crescimento Transformador beta1/genética , Tretinoína/administração & dosagem , Homeobox 1 de Ligação a E-box em Dedo de Zinco
15.
Radiol Case Rep ; 18(4): 1628-1632, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36865620

RESUMO

Intracranial epidermoid cysts (ECs) are encapsulated lesions lined by squamous cell epithelium and the most location is the cerebellopontine angle and appears with cerebrospinal fluid-like irregular mass. Occasionally, ECs present as high-density masses on computed tomography and atypical features in magnetic resonance images in the unusual area, which makes the diagnosis difficult. Here, we report a case of a female subject who complained of episodic left facial convulsions for more than 3 months. Computed tomography plain scan revealed a large hyperdense parasellar mass with atypical magnetic resonance findings. In this report, we analyzed retrospectively the radiological characteristics and histopathology of the parasellar EC, thus increasing awareness about this unusual image features.

16.
ACS Nano ; 17(3): 2840-2850, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36728704

RESUMO

DNA as an exceptional data storage medium offers high information density. However, DNA storage requires specialized equipment and tightly controlled environments for storage. Fast encapsulation within minutes for enhanced DNA stability to do away with specialized equipment and fast DNA extraction remain a challenge. Here, we report a DNA microlibrary that can be encapsulated by metal-organic frameworks (MOFs) within 10 min and extracted (5 min) in a single microfluidic chip for automated and integrated DNA-based data storage. The DNA microlibrary@MOFs enhances the stability of data-encoded DNA against harsh environments. The encoded information can be read out perfectly after accelerated aging, equivalent to being readable after 10 years of storage at 25 °C, 50% relative humidity, and 10 000 lx sunlight radiation. Moreover, the library enables fast retrieval of target data via flow cytometry and can be reproduced after each access.


Assuntos
Estruturas Metalorgânicas , Microfluídica , DNA , Armazenamento e Recuperação da Informação
17.
Quant Imaging Med Surg ; 13(6): 3400-3415, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37284074

RESUMO

Background: The present study aimed to establish a robust predictive model based on a machine learning (ML) algorithm providing preoperative noninvasive diagnosis and to further explore the contribution of each magnetic resonance imaging (MRI) sequence to the classification to help select images for future model development. Methods: This was a retrospective cross-sectional study, and consecutive patients with histologically confirmed diffuse gliomas in our hospital from November 2015 to October 2019 were recruited. The participants were grouped into a training and testing set based on a ratio of 8:2. Five MRI sequences were employed to develop the support vector machine (SVM) classification model. An advanced contrast analysis of single-sequence-based classifiers was performed, according to which different sequence combinations were tested, and the best one was selected to form an ultimate classifier. Patients whose MRIs were acquired with other types of scanners formed an additional, independent validation set. Results: A total of 150 patients with gliomas were used in the present study. Contrast analysis revealed that the contribution of the apparent diffusion coefficient (ADC) was the most significant [accuracies were as follows: histological phenotype, 0.640; isocitrate dehydrogenase (IDH) status, 0.656; and Ki-67 expression, 0.699] and that of T1 weighted imaging was limited (accuracies were as follows: histological phenotype, 0.521; IDH status, 0.492; and Ki-67 expression, 0.556). The ultimate classifiers for IDH status, histological phenotype, and Ki-67 expression achieved promising performances with area under the curve (AUC) values of 0.88, 0.93, and 0.93, respectively. The classifiers for the histological phenotype, IDH status, and Ki-67 expression correctly predicted 3 of 5 subjects, 6 of 7 subjects, and 9 of 13 subjects in the additional validation set, respectively. Conclusions: The present study showed satisfactory performance in predicting the IDH genotype, histological phenotype, and Ki-67 expression level. The contrast analysis revealed the contribution of different MRI sequences and suggested that the combination of all the acquired sequences was not the optimal strategy to build the radiogenomics-based classifier.

18.
Talanta ; 217: 121020, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32498838

RESUMO

Rapid quantification of pathogenic Salmonella Typhimurium (S. Typhimurium) and total bacteria in eggs is highly desired for food safety control. However, the complexity of egg matrix presents a significant challenge for sensitive detection of bacteria. In this study, a sample pretreatment protocol, including dilution, fat dissolution, protein degradation, filtration, and washing was developed to circumvent this challenge. A laboratory-built nano-flow cytometer (nFCM) that is hundreds of fold more sensitive than the conventional flow cytometer was employed to analyze individual bacteria upon nucleic acid and immunofluorescent staining. Eggs spiked with pathogenic S. Typhimurium and harmless Escherichia coli K12 (E. coli K12) were used as the model system to optimize the sample pretreatment protocol. S. Typhimurium and total bacteria in eggs can be quantified without cultural enrichment, and the whole process of sample pretreatment, staining, and instrument analysis can be accomplished within 1.5 h. The bacterial recovery rate upon sample pretreatment, detection limit, and dynamic range for S. Typhimurium in eggs were 92%, 2 × 103 cells/mL, and from 2 × 103 to 4 × 108 cells/mL, respectively. The as-developed approach can specifically distinguish S. Typhimurium from other bacteria and successful application to bacterial detection in eggs freshly purchased from supermarket and spoiled eggs upon inappropriate storage was demonstrated.


Assuntos
Ovos/microbiologia , Citometria de Fluxo , Nanotecnologia , Salmonella typhimurium/isolamento & purificação , Escherichia coli K12/isolamento & purificação
20.
Nat Commun ; 11(1): 3948, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769984

RESUMO

Thalamocortical dysrhythmia is a key pathology of chronic neuropathic pain, but few studies have investigated thalamocortical networks in chronic low back pain (cLBP) given its non-specific etiology and complexity. Using fMRI, we propose an analytical pipeline to identify abnormal thalamocortical network dynamics in cLBP patients and validate the findings in two independent cohorts. We first identify two reoccurring dynamic connectivity states and their associations with chronic and temporary pain. Further analyses show that cLBP patients have abnormal connectivity between the ventral lateral/posterolateral nucleus (VL/VPL) and postcentral gyrus (PoCG) and between the dorsal/ventral medial nucleus and insula in the less frequent connectivity state, and temporary pain exacerbation alters connectivity between the VL/VPL and PoCG and the default mode network in the more frequent connectivity state. These results extend current findings on thalamocortical dysfunction and dysrhythmia in chronic pain and demonstrate that cLBP pathophysiology and clinical pain intensity are associated with distinct thalamocortical network dynamics.


Assuntos
Córtex Cerebral/fisiopatologia , Dor Crônica/fisiopatologia , Núcleos Laterais do Tálamo/fisiopatologia , Dor Lombar/fisiopatologia , Núcleos Ventrais do Tálamo/fisiopatologia , Adulto , Mapeamento Encefálico , Estudos de Casos e Controles , Córtex Cerebral/diagnóstico por imagem , Dor Crônica/diagnóstico , Conjuntos de Dados como Assunto , Feminino , Humanos , Núcleos Laterais do Tálamo/diagnóstico por imagem , Dor Lombar/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/fisiopatologia , Medição da Dor , Núcleos Ventrais do Tálamo/diagnóstico por imagem , Adulto Jovem
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