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1.
Radiother Oncol ; 195: 110221, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38479441

RESUMO

BACKGROUND AND PURPOSE: To develop a computed tomography (CT)-based deep learning model to predict overall survival (OS) among small-cell lung cancer (SCLC) patients and identify patients who could benefit from prophylactic cranial irradiation (PCI) based on OS signature risk stratification. MATERIALS AND METHODS: This study retrospectively included 556 SCLC patients from three medical centers. The training, internal validation, and external validation cohorts comprised 309, 133, and 114 patients, respectively. The OS signature was built using a unified fully connected neural network. A deep learning model was developed based on the OS signature. Clinical and combined models were developed and compared with a deep learning model. Additionally, the benefits of PCI were evaluated after stratification using an OS signature. RESULTS: Within the internal and external validation cohorts, the deep learning model (concordance index [C-index] 0.745, 0.733) was far superior to the clinical model (C-index: 0.635, 0.630) in predicting OS, but slightly worse than the combined model (C-index: 0.771, 0.770). Additionally, the deep learning model had excellent calibration, clinical usefulness, and improved accuracy in classifying survival outcomes. Remarkably, patients at high risk had a survival benefit from PCI in both the limited and extensive stages (all P < 0.05), whereas no significant association was observed in patients at low risk. CONCLUSIONS: The CT-based deep learning model exhibited promising performance in predicting the OS of SCLC patients. The OS signature may aid in individualized treatment planning to select patients who may benefit from PCI.


Assuntos
Irradiação Craniana , Aprendizado Profundo , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Tomografia Computadorizada por Raios X , Humanos , Carcinoma de Pequenas Células do Pulmão/radioterapia , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/patologia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Estudos Retrospectivos , Masculino , Feminino , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-Idade , Irradiação Craniana/métodos , Idoso , Taxa de Sobrevida
2.
Acad Radiol ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38508935

RESUMO

RATIONALE AND OBJECTIVES: Transarterial chemoembolization (TACE) plus molecular targeted therapies has emerged as the main approach for treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). A robust model for outcome prediction and risk stratification of recommended TACE plus molecular targeted therapies candidates is lacking. We aimed to develop an easy-to-use tool specifically for these patients. METHODS: A retrospective analysis was conducted on 384 patients with HCC and PVTT who underwent TACE plus molecular targeted therapies at 16 different institutions. We developed and validated a new prognostic score which called ABPS score. Additionally, an external validation was performed on data from 200 patients enrolled in a prospective cohort study. RESULTS: The ABPS score (ranging from 0 to 3 scores), which involves only Albumin-bilirubin (ALBI, grade 1: 0 score; grade 2: 1 score), PVTT(I-II type: 0 score; III-IV type: 1 score), and systemic-immune inflammation index (SII,<550 × 1012: 0 score; ≥550 × 1012: 1 score). Patients were categorized into three risk groups based on their ABPS score: ABPS-A, B, and C (scored 0, 1-2, and 3, respectively). The concordance index (C-index) of the ABPS scoring system was calculated to be 0.802, significantly outperforming the HAP score (0.758), 6-12 (0.712), Up to 7 (0.683), and ALBI (0.595) scoring systems (all P < 0.05). These research findings were further validated in the external validation cohorts. CONCLUSION: The ABPS score demonstrated a strong association with survival outcomes and radiological response in patients undergoing TACE plus molecular targeted therapy for HCC with PVTT. The ABPS scoring system could serve as a valuable tool to guide treatment selection for these patients.

3.
Adv Sci (Weinh) ; 11(18): e2309748, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38460157

RESUMO

Pulmonary delivery of therapeutic agents has been considered the desirable administration route for local lung disease treatment. As the latest generation of therapeutic agents, nucleic acid has been gradually developed as gene therapy for local diseases such as asthma, chronic obstructive pulmonary diseases, and lung fibrosis. The features of nucleic acid, specific physiological structure, and pathophysiological barriers of the respiratory tract have strongly affected the delivery efficiency and pulmonary bioavailability of nucleic acid, directly related to the treatment outcomes. The development of pharmaceutics and material science provides the potential for highly effective pulmonary medicine delivery. In this review, the key factors and barriers are first introduced that affect the pulmonary delivery and bioavailability of nucleic acids. The advanced inhaled materials for nucleic acid delivery are further summarized. The recent progress of platform designs for improving the pulmonary delivery efficiency of nucleic acids and their therapeutic outcomes have been systematically analyzed, with the application and the perspectives of advanced vectors for pulmonary gene delivery.


Assuntos
Terapia Genética , Ácidos Nucleicos , Humanos , Ácidos Nucleicos/administração & dosagem , Terapia Genética/métodos , Transfecção/métodos , Administração por Inalação , Pneumopatias/terapia , Pneumopatias/genética , Técnicas de Transferência de Genes , Pulmão/metabolismo , Animais
4.
J Imaging Inform Med ; 37(2): 715-724, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38343267

RESUMO

This study aims to assess the effectiveness of radiomics signatures obtained from dual-energy computed tomography enterography (DECTE) in the evaluation of mucosal healing (MH) in patients diagnosed with Crohn's disease (CD). In this study, 106 CD patients with a total of 221 diseased intestinal segments (79 with MH and 142 non-MH) from two medical centers were included and randomly divided into training and testing cohorts at a ratio of 7:3. Radiomics features were extracted from the enteric phase iodine maps and 40-kev and 70-kev virtual monoenergetic images (VMIs) of the diseased intestinal segments, as well as from mesenteric fat. Feature selection was performed using the least absolute shrinkage and selection operator (LASSO) logistic regression. Radiomics models were subsequently established, and the accuracy of these models in identifying MH in CD was assessed by calculating the area under the receiver operating characteristic curve (AUC). The combined-iodine model formulated by integrating the intestinal and mesenteric fat radiomics features of iodine maps exhibited the most favorable performance in evaluating MH, with AUCs of 0.989 (95% confidence interval (CI) 0.977-1.000) in the training cohort and 0.947 (95% CI 0.884-1.000) in the testing cohort. Patients categorized as high risk by the combined-iodine model displayed a greater probability of experiencing disease progression when contrasted with low-risk patients. The combined-iodine radiomics model, which is built upon iodine maps of diseased intestinal segments and mesenteric fat, has demonstrated promising performance in evaluating MH in CD patients.

5.
Radiol Med ; 129(1): 14-28, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37863847

RESUMO

OBJECTIVE: Exploring the efficacy of a Radiological-Clinical (Rad-Clinical) model in predicting prognosis of unresectable hepatocellular carcinoma (HCC) patients after drug eluting beads transcatheter arterial chemoembolization (DEB-TACE) to optimize the targeted sequential treatment. METHODS: In this retrospective analysis, we included 202 patients with unresectable HCC who received DEB-TACE treatment in 17 institutions from June 2018 to December 2022. Progression-free survival (PFS)-related radiomics features were computationally extracted from HCC patients to build a radiological signature (Rad-signature) model with least absolute shrinkage and selection operator regression. A Rad-Clinical model for postoperative PFS was further constructed according to the Rad-signature and clinical variables by Cox regression analysis. It was presented as a nomogram and evaluated by receiver operating characteristic curves, calibration curves, and decision curve analysis. And further evaluate the application value of Rad-Clinical model in clinical stages and targeted sequential therapy of HCC. RESULTS: Tumor size, Barcelona Clinic Liver Cancer (BCLC) stage, and radiomics score (Rad-score) were found to be independent risk factors for PFS after DEB-TACE treatment for unresectable HCC, with the Rad-Clinical model being the greatest predictor of PFS in these patients (hazard ratio: 2.08; 95% confidence interval: 1.56-2.78; P < 0.001) along with high 6 months, 12 months, 18 months, and 24 months area under the curves of 0.857, 0.810, 0.843, and 0.838, respectively. In addition, compared to the radiomics and clinical nomograms, the Radiological-Clinical nomogram also significantly improved the classification accuracy for PFS outcomes, based on the net reclassification improvement (45.2%, 95% CI 0.260-0.632, p < 0.05) and integrated discrimination improvement (14.9%, 95% CI 0.064-0.281, p < 0.05). Based on this model, low-risk patients had higher PFS than high-risk patients in BCLC-B and C stages (P = 0.021). Targeted sequential therapy for patients with high and low-risk HCC in BCLC-B stage exhibited significant benefits (P = 0.018, P = 0.012), but patients with high-risk HCC in BCLC-C stage did not benefit much (P = 0.052). CONCLUSION: The Rad-Clinical model may be favorable for predicting PFS in patients with unresectable HCC treated with DEB-TACE and for identifying patients who may benefit from targeted sequential therapy.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Nomogramas , Estudos Retrospectivos , Terapia de Alvo Molecular , Resultado do Tratamento
6.
Lipids Health Dis ; 22(1): 214, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38049817

RESUMO

BACKGROUND: Steatosis and inflammation are the hallmarks of nonalcoholic steatohepatitis (NASH). Rotundic acid (RA) is among the key triterpenes of Ilicis Rotundae Cortex and has exhibited multipronged effects in terms of lowering the lipid content and alleviating inflammation. The study objective is to systematically evaluate the potential mechanisms through which RA affects the development and progression of NASH. METHODS: Transcriptomic and proteomic analyses of primary hepatocytes isolated from the control, high-fat diet-induced NASH, and RA treatment groups were performed through Gene Ontology analysis and pathway enrichment. Hub genes were identified through network analysis. Integrative analysis revealed key RA-regulated pathways, which were verified by gene and protein expression studies and cell assays. RESULTS: Hub genes were identified and enriched in the Toll-like receptor 4 (TLR4)/activator protein-1 (AP1) signaling pathway and glycolysis pathway. RA reversed glycolysis and attenuated the TLR4/AP1 pathway, thereby reducing lipid accumulation and inflammation. Additionally, lactate release in L-02 cells increased with NaAsO2-treated and significantly decreased with RA treatment, thus revealing that RA had a major impact on glycolysis. CONCLUSIONS: RA is effective in lowering the lipid content and reducing inflammation in mice with NASH by ameliorating glycolysis and TLR4/AP1 pathways, which contributes to the existing knowledge and potentially sheds light on the development of therapeutic interventions for patients with NASH.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Triterpenos , Humanos , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Fígado/metabolismo , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Proteômica , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Transdução de Sinais/genética , Inflamação/metabolismo , Lipídeos , Camundongos Endogâmicos C57BL
7.
Commun Biol ; 6(1): 943, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37714996

RESUMO

During the summer, pregnant ewes experience heat stress, leading to the occurrence of IUGR lambs. This study aims to explore the biomarkers of exosomal miRNAs derived from umbilical plasma in both IUGR and normal Hu lambs. We establish a heat-stressed Hu sheep model during mid-late gestation and selected IUGR and normal lambs for analysis. Exosomes from umbilical plasma were separated and small RNA sequencing is used to identify differentially expressed miRNAs. Next, we utilize MiRanda to predict the target genes of the differentially expressed miRNAs. To further understand the biological significance of these miRNAs, we conduct GO and KEGG pathway enrichment analysis for their target genes. The study's findings indicate that oar-miR-411a-5p is significantly downregulated in exosomes derived from umbilical plasma of IUGR lambs, while oar-miR-200c is significantly upregulated in the HS-IUGR group (P < 0.05). Furthermore, GO and KEGG enrichment analysis demonstrate that the target genes are involved in the Wnt, TGF-beta, and Rap1 signaling pathways. miRNAs found in exosomes have the potential to be utilized as biomarkers for both the diagnosis and treatment of IUGR fetuses.


Assuntos
Exossomos , MicroRNAs , Animais , Feminino , Gravidez , Ovinos , Exossomos/genética , Feto , MicroRNAs/genética , Plasma , Análise de Sequência de RNA
8.
Front Public Health ; 11: 1252103, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37663859

RESUMO

Objective: To explore the current status and interaction of perceived stress, job burnout and mental health among healthcare workers after the opening of COVID-19 which occurred in December 2022. Methods: A cross-sectional study of 792 healthcare workers from three tertiary hospitals in Wuxi was conducted from January 2023 to February 2023. Sociodemographic questionnaire, Perceived Stress Scale, Burnout Scale and Mental Health Self-Assessment Questionnaire were used for investigation. SPSS 26.0 was used to conduct data analysis. The significance of mediation was determined by the PROCESS macro using a bootstrap method. Results: The results showed that (1) The average scores of the participants for perceived stress, mental health and job burnout were 22.65 (7.67), 3.85 (4.21) and 1.88 (1.03), respectively. (2) The perceived stress score, mental health score and job burnout score of healthcare workers were positively correlated (r = 0.543-0.699, p < 0.05). (3) Mental health partially mediated the relationship between perceived stress and job burnout with a mediating effect of 17.17% of the total effect. Job burnout partially mediated the correlation between perceived stress and mental health with a mediating effect of 31.73% of the total effect. Conclusion: The results of this study suggested that perceived stress had an impact on job burnout and mental health, either directly or indirectly. Healthcare managers should intervene to reduce perceived stress to protect healthcare workers' mental health, thereby alleviating burnout under the opening COVID-19 pandemic environment.


Assuntos
COVID-19 , Saúde Mental , Humanos , Estudos Transversais , População do Leste Asiático , Pandemias , COVID-19/epidemiologia , Esgotamento Psicológico , Pessoal de Saúde
9.
Eur J Histochem ; 67(3)2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37548240

RESUMO

Quercetin (Que) has been proven to enhance the chemosensitivity of multiple cancers, including colon cancer (CC). However, whether the combination of Que and 5-fluorouracil (5-FU) has a synergistic effect on drug-resistant CC cells has not previously been reported. The effect of Que (5 and 10 µg/mL) on cell vitality and apoptosis of CC and CC drug-resistant cells was examined using a cell counting kit-8 (CCK-8) and flow cytometry. After cells were treated with 5-FU (10, 40 µg/mL), Que (10 µM, 40 µM), or 5-FU in combination with Que, cell proliferation, apoptosis, oxidative stress-related factors, reactive oxygen species (ROS), and nuclear factor erythroid 2-related factor (Nrf2)/heme oxygenase-1 (HO-1) pathway-related factors were examined by colony formation assay, flow cytometry, ELISA, ROS kit, immunofluorescence assay, and Western blot. The results showed that 5-FU reduced cell viability and induced apoptosis of CC as well as 5-FU-resistant CC cells. Que further restrained the proliferation, oxidative stress-related factors (SOD, CAT, GPx, and GR), ROS production, and induced apoptosis in CC cells and 5-FU-resistant CC cells induced by 5-FU. Moreover, the combination of Que and 5-FU attenuated the Nrf2/HO-1 pathway-related marker levels in CC cells and 5-FU-resistant CC cells. Therefore, our results suggest that Que reverses 5-FU resistance in CC cells via modulating the Nrf2/HO-1 pathway.


Assuntos
Neoplasias do Colo , Quercetina , Humanos , Quercetina/farmacologia , Quercetina/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Heme Oxigenase-1/metabolismo , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Estresse Oxidativo , Apoptose
10.
Radiol Med ; 128(11): 1386-1397, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37597124

RESUMO

PURPOSE: To develop a radiomics nomogram based on computed tomography (CT) to estimate progression-free survival (PFS) in patients with small cell lung cancer (SCLC) and assess its incremental value to the clinical risk factors for individual PFS estimation. METHODS: 558 patients with pathologically confirmed SCLC were retrospectively recruited from three medical centers. A radiomics signature was generated by using the Pearson correlation analysis, univariate Cox analysis, and multivariate Cox analysis. Association of the radiomics signature with PFS was evaluated. A radiomics nomogram was developed based on the radiomics signature, then its calibration, discrimination, reclassification, and clinical usefulness were evaluated. RESULTS: In total, 6 CT radiomics features were finally selected. The radiomics signature was significantly associated with PFS (hazard ratio [HR] 4.531, 95% confidence interval [CI] 3.524-5.825, p < 0.001). Incorporating the radiomics signature into the radiomics nomogram resulted in better performance for the estimation of PFS (concordance index [C-index] 0.799) than with the clinical nomogram (C-index 0.629), as well as high 6 months and 12 months area under the curves of 0.885 and 0.846, respectively. Furthermore, the radiomics nomogram also significantly improved the classification accuracy for PFS outcomes, based on the net reclassification improvement (33.7%, 95% CI 0.216-0.609, p < 0.05) and integrated discrimination improvement (22.7%, 95% CI 0.168-0.278, p < 0.05). Decision curve analysis demonstrated that in terms of clinical usefulness, the radiomics nomogram outperformed the clinical nomogram. CONCLUSION: A CT-based radiomics nomogram exhibited a promising performance for predicting PFS in patients with SCLC, which could provide valuable information for individualized treatment.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Nomogramas , Neoplasias Pulmonares/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Intervalo Livre de Progressão , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
11.
Skin Res Technol ; 29(7): e13394, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37522499

RESUMO

OBJECTIVE: This study explores the applicability and scientific accuracy of instrument measurements in repairing hair products on slightly damaged hair bundles. MATERIALS AND METHOD: Sixty hair bundles mildly damaged with hydrogen peroxide and ammonia standards were divided into two groups: the treatment and control groups (30 hair bundles each). The treatment group used commercial hair care essential oil, whereas the control group used tap water to treat the damage. The two groups were measured using an instrument before and after the product application. The objective indicators included the gloss of hair, along with hair cuticle dynamic friction coefficient, and against hair cuticle dynamic friction coefficient. At the same time, two evaluators conducted sensory evaluations on the gloss and frizz levels of the hair bundles. Therefore, data comparison and verification were carried out together with instrumental measurement data. RESULTS: We verified that the instrumental measurement methods could obtain data trends that are consistent with sensory assessment methods; hence, they have the advantages of accuracy, convenience, and quantifiability. CONCLUSION: Thus, the instrumental measurement methods we verified can provide objective evidence for the efficacy of hair care products in repairing hair.


Assuntos
Preparações para Cabelo , Humanos , Fricção , Cabelo , Preparações para Cabelo/farmacologia
12.
J Biophotonics ; 16(10): e202300077, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37293715

RESUMO

Multi-color two-photon microscopy imaging of live cells is essential in biology. However, the limited diffraction resolution of conventional two-photon microscopy restricts its application to subcellular organelle imaging. Recently, we developed a laser scanning two-photon non-linear structured illumination microscope (2P-NLSIM), whose resolution improved three-fold. However, its ability to image polychromatic live cells under low excitation power has not been verified. Here, to improve the reconstruction super-resolution image quality under low excitation power, we increased the image modulation depth by multiplying the raw images with the reference fringe patterns in the reconstruction process. Simultaneously, we optimized the 2P-NLSIM system to image live cells, including the excitation power, imaging speed, and field of view. The proposed system could provide a new imaging tool for live cells.


Assuntos
Iluminação , Fótons , Microscopia Confocal/métodos
13.
J Appl Biomed ; 21(1): 48-57, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37016778

RESUMO

Oleanolic acid (OA) is a pentacyclic triterpenoid with favourable physiological activity. It is widely distributed in more than 200 species of plants. OA has garnered significant interest because of its potential biological activities, such as antioxidant, bacteriostatic, and hair growth-promoting effects. To study the effect of OA on hair growth and related mechanisms, we investigated hair growth in mice with testosterone-induced androgenetic alopecia (AGA) that were treated with three different concentrations of OA. The antioxidant, bacteriostatic, and cytotoxic effects of OA were evaluated. We found that mice with testosterone-induced AGA treated with 1% or 0.5% OA showed significantly enhanced hair growth and increased vascular endothelial growth factor/glyceraldehyde-3-phosphate dehydrogenase ratio and levels of fibroblast growth factor receptor and insulin-like growth factor 1. Using an immunofluorescence staining assay, we demonstrated that ß-catenin, a key Wnt signalling transducer, was highly expressed in the OA-treated groups. These results suggest that OA may promote hair growth by stimulating hair matrix cell proliferation via the Wnt/ß-catenin pathway and lowering the levels of tumour necrosis factor-alpha, and transforming growth factor-beta 1, dihydrotestosterone, and 5α-reductase.


Assuntos
Ácido Oleanólico , beta Catenina , Camundongos , Animais , beta Catenina/metabolismo , Ácido Oleanólico/farmacologia , Citocinas , Fator A de Crescimento do Endotélio Vascular/metabolismo , Antioxidantes , Alopecia/induzido quimicamente , Alopecia/tratamento farmacológico , Alopecia/metabolismo , Folículo Piloso/metabolismo , Folículo Piloso/patologia , Testosterona
14.
J Steroid Biochem Mol Biol ; 231: 106313, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37075986

RESUMO

Depression is a common mental disorder with an increasing incidence. Several studies have demonstrated that cortical DNA hypomethylation is associated with depression-like behaviors. This study aims to investigate whether maternal vitamin D deficiency (VDD) induces depression-like behaviors and to explore the effects of folic acid supplement on VDD-induced cortical DNA hypomethylation in adult offspring. Female mice were fed with a VDD diet, beginning at 5 weeks of age and throughout pregnancy. Depression-like behaviors were evaluated, and cortical 5-methylcytosine (5mC) content was detected in adult offspring. Results showed that depression-like behaviors were observed in adult offspring of the VDD group. Cortical Ache and Oxtr mRNAs were upregulated in female offspring of the VDD group. Cortical Cpt1a and Htr1b mRNAs were increased in male offspring of the VDD group. Moreover, cortical 5mC content was reduced in offspring of VDD-fed dams. The additional experiment showed that serum folate and cortical S-adenosylmethionine (SAM) contents were decreased in the offspring of the VDD group. Folic acid supplement attenuated VDD-induced SAM depletion and reversed cortical DNA methylation. Moreover, folic acid supplement attenuated VDD-induced upregulation of depression-related genes. In addition, folic acid supplement alleviated maternal VDD-induced depression-like behaviors in adult offspring. These results suggest that maternal VDD induces depression-like behavior in adult offspring by reducing cortical DNA methylation. The gestational folic acid supplement prevents VDD-induced depression-like behavior by reversing cortical DNA hypomethylation in adult offspring.


Assuntos
Ácido Fólico , Deficiência de Vitamina D , Gravidez , Animais , Masculino , Feminino , Camundongos , Ácido Fólico/farmacologia , Metilação de DNA , Depressão/etiologia , Depressão/prevenção & controle , DNA
15.
Genome Biol ; 24(1): 49, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36918913

RESUMO

BACKGROUND: The epidermis of cotton ovule produces fibers, the most important natural cellulose source for the global textile industry. However, the molecular mechanism of fiber cell growth is still poorly understood. RESULTS: Here, we develop an optimized protoplasting method, and integrate single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) to systematically characterize the cells of the outer integument of ovules from wild type and fuzzless/lintless (fl) cotton (Gossypium hirsutum). By jointly analyzing the scRNA-seq data from wildtype and fl, we identify five cell populations including the fiber cell type and construct the development trajectory for fiber lineage cells. Interestingly, by time-course diurnal transcriptomic analysis, we demonstrate that the primary growth of fiber cells is a highly regulated circadian rhythmic process. Moreover, we identify a small peptide GhRALF1 that circadian rhythmically controls fiber growth possibly through oscillating auxin signaling and proton pump activity in the plasma membrane. Combining with scATAC-seq, we further identify two cardinal cis-regulatory elements (CREs, TCP motif, and TCP-like motif) which are bound by the trans factors GhTCP14s to modulate the circadian rhythmic metabolism of mitochondria and protein translation through regulating approximately one third of genes that are highly expressed in fiber cells. CONCLUSIONS: We uncover a fiber-specific circadian clock-controlled gene expression program in regulating fiber growth. This study unprecedentedly reveals a new route to improve fiber traits by engineering the circadian clock of fiber cells.


Assuntos
Fibra de Algodão , Gossypium , Perfilação da Expressão Gênica , Fenótipo , Expressão Gênica , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
16.
Hum Exp Toxicol ; 42: 9603271221149656, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36607285

RESUMO

BACKGROUND: Hyperglycemia is closely related to adverse pregnancy outcomes including pre-eclampsia (PE), a life-threatening complication with a substantial morbidity and mortality. However, the pathogenesis of abnormal placentation in gestational diabetes mellitus (GDM)-associated PE remains elusive. METHOD: Here we isolated exosomes from the human umbilical vein endothelial cells (HUVECs) treated with normal level of glucose (NG) and high levels of glucose (HG). The exosomes were added to HTR-8a/SVneo cells, a trophoblast cell line. High-throughput RNA-sequencing was performed to analyzed the changed RNAs in the exosomes and exosome-treated HTR-8a/SVneo cells. HTR-8a/SVneo cell phenotypes were evaluated from the aspects of cell proliferation, cell invasion and DNA damage. RESULTS: After treatment with HG, the changed RNAs in exosomes was enriched in RNA stabilization and oxidative stress. The altered RNAs in the HTR-8a/SVneo cells treated with exosomes from HG-induced HUVECs were enriched in pathways related to cell adhesion, migration, DNA damage response and angiogenesis. The HG-induced exosomes impaired the proliferation and invasion of HTR-8a cells and caused the DNA damage. HG up-regulated PUM2 in the exosomes and exosome-treated HTR-8a/SVneo cells. PUM2 interacted with SOX2 mRNA, resulting in the mRNA degradation. Overexpression of SOX2 prevented the damage to HTR-8a/SVneo cells caused by the exosomes from HG-induced HUVECs. CONCLUSIONS: We demonstrate that high glucose-induced endothelial exosomes mediate abnormal phenotypes of trophoblasts through PUM2-mediated repression of SOX2. Our results reveal a novel regulatory mechanism of hyperglycemia in development of abnormal placentation and provide potential targets for preventing adverse pregnancy outcomes.


Assuntos
Exossomos , Hiperglicemia , Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Placentação , Trofoblastos , Exossomos/metabolismo , Hiperglicemia/complicações , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Pré-Eclâmpsia/genética , Glucose/farmacologia , RNA/metabolismo , Movimento Celular , Proliferação de Células , Proteínas de Ligação a RNA/metabolismo , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo
17.
Acta Radiol ; 64(3): 1194-1204, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35971221

RESUMO

BACKGROUND: The prognosis of lung cancer varies widely, even in cases wherein the tumor stage, genetic mutation, and treatment regimens are the same. Thus, an effective means for risk stratification of patients with lung cancer is needed. PURPOSE: To develop and validate a combined model for predicting progression-free survival and risk stratification in patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) treated with ensartinib. MATERIAL AND METHODS: We analyzed 203 tumor lesions in 114 patients and evaluated average radiomic feature measures from all lesions at baseline and changes in these features after early treatment (Δradiomic features). Combined models were developed by integrating clinical with radiomic features. The prediction performance and clinical value of the proposed models were evaluated using receiver operating characteristic analysis, calibration curve, decision curve analysis (DCA), and Kaplan-Meier survival analysis. RESULTS: Both the baseline and delta combined models achieved predictive efficacy with a high area under the curve. The calibration curve and DCA indicated the high accuracy and clinical usefulness of the combined models for tumor progression prediction. In the Kaplan-Meier analysis, the delta and baseline combined models, Δradiomic signature, and two selected clinical features could distinguish patients with a higher progression risk within 42 weeks. The delta combined model had the best performance. CONCLUSION: The combination of clinical and radiomic features provided a prognostic value for survival and progression in patients with NSCLC receiving ensartinib. Radiomic-signature changes after early treatment could be more valuable than those at baseline alone.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Quinase do Linfoma Anaplásico/genética , Quinase do Linfoma Anaplásico/uso terapêutico , Intervalo Livre de Progressão , Prognóstico
18.
Front Immunol ; 14: 1325530, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38259476

RESUMO

Neuroinflammation has been identified as another significant pathogenic factor in Alzheimer's disease following Aß amyloid deposition and tau protein hyperphosphorylation, activated in the central nervous system by glial cells in response to injury-related and pathogen-related molecular patterns. Moderate glial cell activity can be neuroprotective; however, excessive glial cell activation advances the pathology of Alzheimer's disease and is accompanied by structural changes in the brain interface, with peripheral immune cells entering the brain through the blood-brain barrier, creating a vicious circle. The immunomodulatory properties of mesenchymal stem cells (MSCs) are primarily conveyed through extracellular vesicles (EVs). MSC-EVs participate in chronic inflammatory and immune processes by transferring nucleic acids, proteins and lipids from the parent cell to the recipient cell, thus MSC-EVs retain their immunomodulatory capacity while avoiding the safety issues associated with living cell therapy, making them a promising focus for immunomodulatory therapy. In this review, we discuss the modulatory effects of MSC-EVs on Alzheimer's disease-associated immune cells and the mechanisms involved in their treatment of the condition. We have found a clinical trial of MSC-EVs in Alzheimer's disease treatment and outlined the challenges of this approach. Overall, MSC-EVs have the potential to provide a safe and effective treatment option for Alzheimer's disease by targeting neuroinflammation.


Assuntos
Doença de Alzheimer , Vesículas Extracelulares , Células-Tronco Mesenquimais , Humanos , Doença de Alzheimer/terapia , Doenças Neuroinflamatórias , Imunomodulação
19.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 39(6): 1218-1232, 2022 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-36575092

RESUMO

In recent years, the task of object detection and segmentation in medical image is the research hotspot and difficulty in the field of image processing. Instance segmentation provides instance-level labels for different objects belonging to the same class, so it is widely used in the field of medical image processing. In this paper, medical image instance segmentation was summarized from the following aspects: First, the basic principle of instance segmentation was described, the instance segmentation models were classified into three categories, the development context of the instance segmentation algorithm was displayed in two-dimensional space, and six classic model diagrams of instance segmentation were given. Second, from the perspective of the three models of two-stage instance segmentation, single-stage instance segmentation and three-dimensional (3D) instance segmentation, we summarized the ideas of the three types of models, discussed the advantages and disadvantages, and sorted out the latest developments. Third, the application status of instance segmentation in six medical images such as colon tissue image, cervical image, bone imaging image, pathological section image of gastric cancer, computed tomography (CT) image of lung nodule and X-ray image of breast was summarized. Fourth, the main challenges in the field of medical image instance segmentation were discussed and the future development direction was prospected. In this paper, the principle, models and characteristics of instance segmentation are systematically summarized, as well as the application of instance segmentation in the field of medical image processing, which is of positive guiding significance to the study of instance segmentation.


Assuntos
Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Imageamento Tridimensional/métodos , Tomografia Computadorizada por Raios X/métodos , Algoritmos
20.
Microbiol Spectr ; 10(5): e0111522, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36214702

RESUMO

Blood-sucking ticks are obligate parasites and vectors of a variety of human and animal viruses. Some tick-borne viruses have been identified as pathogens of infectious diseases in humans or animals, potentially imposing significant public health burdens and threats to the husbandry industry. Therefore, identifying the profiles of tick-borne viruses will provide valuable information about the evolution and pathogen ecology of tick-borne viruses. In this study, we investigated the viromes of parasitic ticks collected from the body surfaces of herbivores in Xinjiang Uyghur Autonomous Region and Inner Mongolia Autonomous Region of China, two regions in northwest China. By using a metatranscriptomic approach, 17 RNA viruses with high diversity in genomic organization and evolution were identified. Among them, nine are proposed to be novel species. The classified viruses belonged to six viral families, including Phenuiviridae, Rhabdoviridae, Peribunyaviridae, Lispiviridae, Chuviridae, and Reoviridae, and unclassified viruses were also identified. In addition, although some viruses from different sampling locations shared significant similarities, the abundance and diversity of viruses notably varied among the different collection locations. This study demonstrates the diversity of tick-borne viruses in Xinjiang and Inner Mongolia and provides informative data for further study of the evolution and pathogenicity of these RNA viruses. IMPORTANCE Ticks are widely distributed in pastoral areas in northwestern China and act as vectors that carry and transmit a variety of pathogens, especially viruses. Our study revealed the diversity of tick viruses in Xinjiang and Inner Mongolia and uncovered the phylogenetic relationships of some RNA viruses, especially the important zoonotic tick-borne severe fever with thrombocytopenia syndrome virus in Inner Mongolia. These data suggest a complex and diverse evolutionary history and potential ecological factors associated with pathogenic viruses. The pathogenicity of these tick-borne viruses currently remains unclear. Therefore, future research should focus on evaluating the transmissability and pathogenicity of these tick-borne viruses.


Assuntos
Phlebovirus , Vírus de RNA , Doenças Transmitidas por Carrapatos , Carrapatos , Vírus , Humanos , Animais , Filogenia , Viroma/genética , Phlebovirus/genética , Vírus de RNA/genética , China , Vírus/genética , Doenças Transmitidas por Carrapatos/epidemiologia
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