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1.
Med Phys ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38801342

RESUMO

BACKGROUND: 2D CT image-guided radiofrequency ablation (RFA) is an exciting minimally invasive treatment that can destroy liver tumors without removing them. However, CT images can only provide limited static information, and the tumor will move with the patient's respiratory movement. Therefore, how to accurately locate tumors under free conditions is an urgent problem to be solved at present. PURPOSE: The purpose of this study is to propose a respiratory correlation prediction model for mixed reality surgical assistance system, Riemannian and Multivariate Feature Enhanced Temporal Convolutional Network (R-MFE-TCN), and to achieve accurate respiratory correlation prediction. METHODS: The model adopts a respiration-oriented Riemannian information enhancement strategy to expand the diversity of the dataset. A new Multivariate Feature Enhancement module (MFE) is proposed to retain respiratory data information, so that the network can fully explore the correlation of internal and external data information, the dual-channel is used to retain multivariate respiratory feature, and the Multi-headed Self-attention obtains respiratory peak-to-valley value periodic information. This information significantly improves the prediction performance of the network. At the same time, the PSO algorithm is used for hyperparameter optimization. In the experiment, a total of seven patients' internal and external respiratory motion trajectories were obtained from the dataset, and the first six patients were selected as the training set. The respiratory signal collection frequency was 21 Hz. RESULTS: A large number of experiments on the dataset prove the good performance of this method, which improves the prediction accuracy while also having strong robustness. This method can reduce the delay deviation under long window prediction and achieve good performance. In the case of 400 ms, the average RMSE and MAE are 0.0453  and 0.0361 mm, respectively, which is better than other research methods. CONCLUSION: The R-MFE-TCN can be extended to respiratory correlation prediction in different clinical situations, meeting the accuracy requirements for respiratory delay prediction in surgical assistance.

2.
J Am Chem Soc ; 146(22): 15186-15197, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38789930

RESUMO

Effective antitumor immunity hinges on the specific engagement between tumor and cytotoxic immune cells, especially cytotoxic T cells. Although investigating these intercellular interactions is crucial for characterizing immune responses and guiding immunotherapeutic applications, direct and quantitative detection of tumor-T cell interactions within a live-cell context remains challenging. We herein report a photocatalytic live-cell interaction labeling strategy (CAT-Cell) relying on the bioorthogonal decaging of quinone methide moieties for sensitive and selective investigation and quantification of tumor-T cell interactions. By developing quinone methide-derived probes optimized for capturing cell-cell interactions (CCIs), we demonstrated the capacity of CAT-Cell for detecting CCIs directed by various types of receptor-ligand pairs (e.g., CD40-CD40L, TCR-pMHC) and further quantified the strengths of tumor-T cell interactions that are crucial for evaluating the antitumor immune responses. We further applied CAT-Cell for ex vivo quantification of tumor-specific T cell interactions on splenocyte and solid tumor samples from mouse models. Finally, the broad compatibility and utility of CAT-Cell were demonstrated by integrating it with the antigen-specific targeting system as well as for tumor-natural killer cell interaction detection. By leveraging the bioorthogonal photocatalytic decaging chemistry on quinone methide, CAT-Cell provides a sensitive, tunable, universal, and noninvasive toolbox for unraveling and quantifying the crucial but delicate tumor-immune interactions under live-cell settings.


Assuntos
Indolquinonas , Indolquinonas/química , Animais , Camundongos , Humanos , Comunicação Celular , Linhagem Celular Tumoral , Neoplasias/imunologia
3.
Environ Toxicol ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581187

RESUMO

INTRODUCTION: Bladder cancer (BLCA) is a prevalent and deadly form of urinary cancer, and there is a need for effective therapies, particularly for muscle-invasive bladder cancer (MIBC). Cell cycle inhibitors show promise in restoring control of the cell cycle in BLCA cells, but their clinical prognosis evaluation is limited. METHODS: Transcriptome and scRNA-seq data were collected from the Cancer Genome Atlas Program (TCGA)-BLCA and GSE190888 cohort, respectively. R software and the Seurat package were used for data analysis, including cell quality control, dimensionality reduction, and identification of differentially expressed genes. Genes related to the cell cycle were obtained from the genecards website, and a protein-protein interaction network analysis was performed using cytoscape software. Functional enrichment analysis, immune infiltration analysis, drug sensitivity analysis, and molecular docking were conducted using various tools and packages. BLCA cell lines were cultured and transfected for in vitro experimental assays, including RT-qPCR analysis, and CCK-8 cell viability assays. RESULTS: We identified 32 genes as independent risk or protective factors for BLCA prediction. Functional enrichment analysis revealed their involvement in cell cycle regulation, apoptosis, and various signaling pathways. Using these genes, we developed a nomogram for predicting BLCA survival, which displayed high prognosis stratification efficacy in BLCA patients. Four cell cycle associated key genes identified, including NCAM1, HBB, CKD6, and CTLA4. We also identified the main cell types in BLCA patients and investigated the functional differences between epithelial cells based on their expression levels of key genes. Furthermore, we observed a high positive correlative relationship between the infiltration of cancer-associated fibroblasts and the risk score value. Finally, we conducted in vitro experiments to demonstrate the suppressive role of NCAM1 in BLCA cell proliferation. CONCLUSION: These findings suggest that cell cycle associated genes could serve as potential biomarkers for predicting BLCA prognosis and may represent therapeutic targets for the development of more effective therapies. Hopefully, these findings provide valuable insights into the molecular mechanisms and potential therapeutic targets in BLCA from the perspective of cell cycle. Moreover, NCAM1 was a novel cell proliferation suppressor in the BLCA carcinogenesis.

4.
Antioxidants (Basel) ; 13(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38539843

RESUMO

Alzheimer's disease is a neurodegeneration with protein deposits, altered proteolysis, and inflammatory and oxidative processes as major hallmarks. Despite the continuous search for potential therapeutic treatments, no cure is available to date. The use of natural molecules as adjuvants in the treatment of Alzheimer's disease is a very promising strategy. In this regard, ginsenosides from ginseng root show a variety of biological effects. Here, we dissected the role of ginsenosides Rg1 and Rg2 in modulating autophagy and oxidative stress in neuroblastoma cells overexpressing Aß(1-42). Key hallmarks of these cellular processes were detected through immunomethods and fluorometric assays. Our findings indicate that ginsenosides are able to upregulate autophagy in neuronal cells as demonstrated by increased levels of LC3II and Beclin-1 proteins and decreased amounts of p62. Simultaneously, an activation of lysosomal hydrolases was observed. Furthermore, autophagy activation promoted the clearance of Aß(1-42). Rg1 and Rg2 also reduced oxidative stress sources and macromolecule oxidation, promoting NRF2 nuclear translocation and the expression of antioxidant enzymes. Our data further clarify the mechanisms of action of Rg1 and Rg2, indicating new insights into their role in the management of disorders like Alzheimer's disease.

5.
BMC Public Health ; 24(1): 653, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429770

RESUMO

Bulimia, which means a person has episodes of eating a very large amount of food (bingeing) during which the person feels a loss of control over their eating, is the most primitive reason for being overweight and obese. The extended literature has indicated that childhood emotional abuse has a close relationship with adverse mood states, bulimia, and obesity. To comprehensively understand the potential links among these factors, we evaluated a multiple mediation model in which anxiety/depression and bulimia were mediators between childhood emotional abuse and body mass index (BMI). A set of self-report questionnaires, including the Childhood Trauma Questionnaire (CTQ), Beck Anxiety Inventory, Beck Depression Inventory (BDI), and Eating Disorder Inventory (EDI), was sent out. Clinical data from 37 obese patients (age: 29.65 ± 5.35, body mass index (BMI): 37.59 ± 6.34) and 37 demographically well-matched healthy people with normal body weight (age: 31.35 ± 10.84, BMI: 22.16 ± 3.69) were included in the investigation. We first performed an independent t-test to compare all scales or subscale scores between the two groups. Then, we conducted Pearson correlation analysis to test every two variables' pairwise correlation. Finally, multiple mediation analysis was performed with BMI as the outcome variable, and childhood emotional abuse as the predictive variable. Pairs of anxiety, bulimia, and depression, bulimia were selected as the mediating variables in different multiple mediation models separately. The results show that the obese group reported higher childhood emotional abuse (t = 2.157, p = 0.034), worse mood state (anxiety: t = 5.466, p < 0.001; depression: t = 2.220, p = 0.030), and higher bulimia (t = 3.400, p = 0.001) than the healthy control group. Positive correlations were found in every pairwise combination of BMI, childhood emotional abuse, anxiety, and bulimia. Multiple mediation analyses indicate that childhood emotional abuse is positively linked to BMI (ß = 1.312, 95% CI = 0.482-2.141). The model using anxiety and bulimia as the multiple mediating variables is attested to play roles in the relationship between childhood emotional abuse and obesity (indirect effect = 0.739, 95% CI = 0.261-1.608, 56.33% of the total effect). These findings confirm that childhood emotional abuse contributes to adulthood obesity through the multiple mediating effects of anxiety and bulimia. The present study adds another potential model to facilitate our understanding of the eating psychopathology of obesity.


Assuntos
Cirurgia Bariátrica , Bulimia , Testes Psicológicos , Autorrelato , Adulto , Humanos , Adulto Jovem , Bulimia/epidemiologia , Abuso Emocional , Ansiedade/epidemiologia , Obesidade/epidemiologia , Obesidade/psicologia
6.
J Gene Med ; 26(1): e3655, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38282148

RESUMO

BACKGROUND: A prognostic model of bladder cancer was constructed based on costimulatory molecules, and its stability and accuracy were verified in different datasets. METHOD: The expression profile of bladder cancer RNA and the corresponding clinical data in The Cancer Genome Atlas (TCGA) database were analyzed employing computational biology, and a prognostic model was constructed for costimulating molecule-related genes. The model was applied in GSE160693, GSE176307, Xiangya_Cohort, GSE13507, GSE19423, GSE31684, GSE32894, GSE48075, GSE69795 and GSE70691 in TCGA dataset and Gene Expression Omnibus database. The role of costimulating molecules in bladder cancer tumor subtypes was also explored. By consistent cluster analysis, bladder cancer in the TCGA dataset was categorized into two subtypes: C1 and C2. The C1 subtype exhibited a poor prognosis, high levels of immune cell infiltration and significant enrichment of natural killer cells, T cells and dendritic cells in the C1 subtype. In addition, the ImmuneScore calculated by the ESTIMATE algorithm differed greatly between the two subtypes, and the ImmuneScore of the C1 subtype was greater than the C2 subtype in a significant manner. RESULTS: This study also assessed the relationship between costimulating molecules and immunotherapy response. The high-risk group responded poorly to immunotherapy, with significant differences in the amount of most immune cells between the two groups. Further, three indices of the ESTIMATE algorithm and 22 immune cells of the CIBERSORT algorithm were significantly correlated with risk values. These findings suggest the potential value of costimulating molecules in predicting immunotherapy response. CONCLUSION: A costimulatory molecule-based prognostic model for bladder cancer was established and validated across multiple datasets. This model introduces a novel mode for tailoring treatments to each individual with bladder cancer, and offers valuable insights for informed clinical choices. Simultaneously, this research also delved into the significance of costimulating molecules within distinct bladder cancer subtypes, shedding novel insights into improving immunotherapy strategies for the treatment of bladder cancer.


Assuntos
Neoplasias da Bexiga Urinária , Humanos , Prognóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/terapia , Imunoterapia , Algoritmos , Análise por Conglomerados
7.
Nutr Clin Pract ; 39(3): 702-713, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38161144

RESUMO

BACKGROUND: Ambulatory cancer patients are at high risk of malnutrition. Multiple nutrition screening and assessment tools are used in the outpatient setting. This study aimed to evaluate the efficacy of different nutrition screening tools as the first step of the Global Leadership Initiative on Malnutrition (GLIM) framework in Chinese ambulatory cancer patients. METHODS: A cross-sectional study was conducted in a tertiary hospital in China. Malnutrition diagnoses made by the GLIM framework using Malnutrition Screening Tool, Malnutrition Universal Screening Tool, Nutritional Risk Screening 2002, or short-form of Patient-Gernerated Subjective Global Assessment (PG-SGA) as the first step were compared with PG-SGA separately. RESULTS: Of the 562 included patients, 31.0% were diagnosed with malnutrition (PG-SGA: B + C), and 12.6% were diagnosed with severe malnutrition (PG-SGA: C). As the screening tool in the first step of the GLIM framework, the short form of PG-SGA (PG-SGA SF) with a cutoff value of ≥2 performed best in diagnosing malnutrition, with good sensitivity (SE) (80.5% [73.6-85.9]) and specificity (SP) (98.4% [96.5-99.4]) and substantial accordance (κ = 0.826), whereas PG-SGA SF with a cutoff value of ≥4 performed best in diagnosing severe malnutrition, with fair SE (62.0% [49.6-73.0]), good SP (96.7% [94.6-98.1]) and moderate accordance (κ = 0.629). CONCLUSION: Using PG-SGA as the standard, the GLIM framework using PG-SGA SF as the screening tool has good accordance with the PG-SGA regardless of severity grading. PG-SGA SF can be used as a valid screening tool in the GLIM framework.


Assuntos
Desnutrição , Programas de Rastreamento , Neoplasias , Avaliação Nutricional , Pacientes Ambulatoriais , Humanos , Estudos Transversais , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Feminino , Pessoa de Meia-Idade , Masculino , Neoplasias/complicações , Neoplasias/diagnóstico , China/epidemiologia , Idoso , Programas de Rastreamento/métodos , Pacientes Ambulatoriais/estatística & dados numéricos , Estado Nutricional , Sensibilidade e Especificidade , Adulto , População do Leste Asiático
8.
Transl Cancer Res ; 12(10): 2582-2595, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37969391

RESUMO

Background: The aberrant expression of the classical tumor suppressor gene p16 is a frequent event in lung cancer mainly due to the hypermethylation of its 5'-cytosine-phosphate-guanine-3' island (Cgi). However, whether methylation happens in other regions and how p16 expression and function are affected are largely unknown. Methods: Clustered Regularly Interspaced Short Palindromic Repeats/dCas9 (CRISPR/dCas9) technology was used for methylation editing at specific site of p16. The effects of methylation editing were detected by 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium, inner salt (MTS), transwell migration and wound healing tests. Chromatin immnoprecipitation-quantitative polymerase chain reaction (CHIP-qPCR) was performed to explore the impact of Cgi shore methylation on the binding abilities of transcription factors (TFs) including YY1, SP1, ZNF148 and OTX2 to p16 gene. A rescue experiment was performed to verify the regulatory effect of OTX2 on p16. The negative relationship between p16 expression and the methylation level of Cgi shore in non-promoter region was further verified with datasets from The Cancer Genome Atlas (TCGA) program and lung adenocarcinoma (LUAD) patients' samples. Results: The suppressive effect of p16 Cgi shore methylation on its expression was demonstrated in both HEK293 and A549 cells using CRISPR/dCas9-mediated specific site methylation editing. Methylation of the Cgi shore in the p16 non-promoter region significantly decreased its expression and promoted cell growth and migration. The ability of OTX2 bound to p16 was significantly reduced by 19.35% after methylation modification. Over-expression of OTX2 in A549 cells partly reversed the inhibitory effect of methylation on p16 expression by 19.04%. The verification results with TCGA and LUAD patients' samples supported that the p16 Cgi shore is a key methylation regulatory region. Conclusions: Our findings suggested that methylation of the Cgi shore in the p16 non-promoter region can hamper the transcriptional activity of OTX2, leading to a reduction in the expression of p16, which might contribute to the development of lung cancer.

9.
BMC Gastroenterol ; 23(1): 308, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37700238

RESUMO

PURPOSE: To study the combined model of radiomic features and clinical features based on enhanced CT images for noninvasive evaluation of microsatellite instability (MSI) status in colorectal liver metastasis (CRLM) before surgery. METHODS: The study included 104 patients retrospectively and collected CT images of patients. We adjusted the region of interest to increase the number of MSI-H images. Radiomic features were extracted from these CT images. The logistic models of simple clinical features, simple radiomic features, and radiomic features with clinical features were constructed from the original image data and the expanded data, respectively. The six models were evaluated in the validation set. A nomogram was made to conveniently show the probability of the patient having a high MSI (MSI-H). RESULTS: The model including radiomic features and clinical features in the expanded data worked best in the validation group. CONCLUSION: A logistic regression prediction model based on enhanced CT images combining clinical features and radiomic features after increasing the number of MSI-H images can effectively identify patients with CRLM with MSI-H and low-frequency microsatellite instability (MSI-L), and provide effective guidance for clinical immunotherapy of CRLM patients with unknown MSI status.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Instabilidade de Microssatélites , Estudos Retrospectivos , Repetições de Microssatélites , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirurgia , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/genética
10.
Cancer Lett ; 577: 216409, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-37748723

RESUMO

The cGAS-STING signaling is an important pathway involved in the regulation of tumor microenvironment, which affects many cellular functions including immune activation. Its role in combating tumor progression is widely recognized, especially with its function in inducing innate and adaptive immune responses, on which many immunotherapies have been developed. However, a growing number of findings also suggest a diversity of its roles in shaping tumor microenvironment, including functions that promote tumor progression. Here, we summarize the functions of the cGAS-STING signaling in tumor microenvironment to maintain tumor survival and proliferation through facilitating the forming of an immunosuppressive tumor microenvironment and discuss the current advances of STING-related immunotherapies.


Assuntos
Neoplasias , Microambiente Tumoral , Humanos , Imunidade Inata , Imunossupressores , Neoplasias/terapia , Nucleotidiltransferases/genética , Transdução de Sinais
11.
Heliyon ; 9(8): e18886, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37600377

RESUMO

Introduction: Thyroid cancer (TC), a common endocrine malignant tumor with a higher incidence in females than in males, is a serious threat to human life and health. Although current clinical treatments can alleviate this disease, the recurrence rate remains high. Tuber Dioscoreae Bulbiferae, also called Huang-Yao-Zi (HYZ), has remarkable curative properties, few side effects and is used for the treatment of sore throat, goiter, hemoptysis, and other diseases in traditional Chinese medicine (TCM). Existing clinical studies have found that HYZ can improve the clinical symptoms of TC patients and reduce tumor volume, while in vitro studies have found that HYZ can induce the death of thyroid cancer cells. However, the mechanism of HYZ in the treatment of TC is still unclear. Methods: In this study, based on network pharmacology and bioinformatics, the target and molecular mechanism of HYZ in the treatment of TC were preliminarily explored. The results suggest that the antithyroid cancer effect of HYZ may be related to the PI3K-Akt and focal adhesion pathways. Then, a TC cell model was established to further explore the detail molecular mechanisms. Results: Fortunately, HYZ induced apoptosis in KMH-2 cells and regulated the expression of apoptosis-related proteins and genes. At the same time, HYZ can also significantly inhibit the migration and invasion of TC cells. Further studies showed that the pharmacological activities of HYZ were related to the regulation of the PI3K-Akt and focal adhesion pathways. Conclusion: Our study provides a reference for further animal or clinical studies investigating the effectiveness and molecular mechanisms of HYZ against thyroid cancer.

13.
Zhongguo Yi Liao Qi Xie Za Zhi ; 47(3): 332-336, 2023 May 30.
Artigo em Chinês | MEDLINE | ID: mdl-37288640

RESUMO

Products made from allogeneic tissue are largely used in clinical treatment due to its wide source compared with autologous tissue, causing less secondary trauma of patients and the good biocompatibility. Various organic solvents and other substances introduced in the production process of allogeneic products will leach down into the human through clinical treatment, thus bringing varying degrees of harm to patients. Therefore, it is very necessary to detect and control the leachables in such products. Based on the classification and summary of leachable substances existing in the allogeneic products, the preparation of extract and the establishment of the detection techniques for known and unknown leachable are briefly introduced in this study, in order to provide research method for the study of leachable substances of allogeneic products.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Humanos , Embalagem de Medicamentos
14.
Nat Commun ; 14(1): 2484, 2023 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-37120608

RESUMO

Tissues are highly complicated with spatial heterogeneity in gene expression. However, the cutting-edge single-cell RNA-seq technology eliminates the spatial information of individual cells, which contributes to the characterization of cell identities. Herein, we propose single-cell spatial position associated co-embeddings (scSpace), an integrative method to identify spatially variable cell subpopulations by reconstructing cells onto a pseudo-space with spatial transcriptome references (Visium, STARmap, Slide-seq, etc.). We benchmark scSpace with both simulated and biological datasets, and demonstrate that scSpace can accurately and robustly identify spatially variated cell subpopulations. When employed to reconstruct the spatial architectures of complex tissue such as the brain cortex, the small intestinal villus, the liver lobule, the kidney, the embryonic heart, and others, scSpace shows promising performance on revealing the pairwise cellular spatial association within single-cell data. The application of scSpace in melanoma and COVID-19 exhibits a broad prospect in the discovery of spatial therapeutic markers.


Assuntos
COVID-19 , Análise de Célula Única , Humanos , Análise de Célula Única/métodos , Transcriptoma , Análise de Sequência de RNA/métodos , Perfilação da Expressão Gênica/métodos
15.
J Cereb Blood Flow Metab ; 43(7): 1194-1205, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36883376

RESUMO

The association of exosomal RNA profiling and pathogenesis of moyamoya disease (MMD) and intracranial Atherosclerotic disease (ICAD) is unknown. In this study, we investigated the RNA profiles of sEV (small extracellular vesicles)/exosomes in patients with MMD and ICAD. Whole blood samples were collected from 30 individuals, including 10 patients with MMD, 10 patients with ICAD, and 10 healthy individuals. Whole transcriptome analysis was performed using the GeneChip WT Pico Reagent kit. Transcriptional correlation was verified using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The association between functional dysregulation and candidate RNAs was studied in vitro. In total, 1,486 downregulated and 2,405 upregulated RNAs differed significantly between patients with MMD and healthy controls. Differential expression of six circRNAs was detected using qPCR. Among these significantly differentially expressed RNAs, IPO11 and PRMT1 circRNAs were upregulated, whereas CACNA1F circRNA was downregulated. This is the first study showing that the differential expression of exosomal RNAs associated with MMD pathogenesis, such as overexpression of IPO11 and PRMT1 circRNAs, may be related to angiogenesis in MMD. The downregulation of CACNA1F circRNA may be related to vascular occlusion. These results propose the utility of exosomal RNAs as biological markers in MMD.


Assuntos
Exossomos , Doença de Moyamoya , Humanos , RNA/genética , RNA/metabolismo , RNA Circular/genética , Exossomos/genética , Exossomos/metabolismo , Doença de Moyamoya/genética , Perfilação da Expressão Gênica/métodos , Biomarcadores , Proteína-Arginina N-Metiltransferases/metabolismo , Proteínas Repressoras/genética , beta Carioferinas/genética
16.
J Hazard Mater ; 443(Pt A): 130191, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36272375

RESUMO

Cadmium (Cd) is a common environmental pollutant that can damage multiple organs, including the kidney. To prevent renal effects, international authorities have set health-based guidance values of Cd from epidemiological studies. To explore the health risk of Cd exposure and whether human equivalent doses (HEDs) derived from in vitro tests match the current guidance values, we integrated renal tubular epithelial cell-based assays with a physiologically based toxicokinetic model combined with the Monte Carlo method. For females, the HEDs (µg/kg/week) derived from KE2 (DNA damage), KE3 (cell cycle arrest), and KE4 (apoptosis) were 0.20 (2.5th-97.5th percentiles: 0.09-0.48), 0.52 (0.24-1.26), and 2.73 (1.27-6.57), respectively; for males the respective HEDs were 0.23 (0.10-0.49), 0.60 (0.27-1.30), and 3.11 (1.39-6.78). Among them, HEDKE4 (female) was close to the tolerable weekly intake (2.5 µg/kg/week) set by the European Food Safety Authority. The margin of exposure (MOE) derived from HEDKE4 (female) indicated that risks of renal toxicity for populations living in cadmium-contaminated regions should be of concern. This study provided a new approach methodology (NAM) for environmental chemical risk assessment using in silico and in vitro methods.


Assuntos
Cádmio , Poluentes Ambientais , Masculino , Feminino , Humanos , Cádmio/toxicidade , Cádmio/análise , Toxicocinética , Medição de Risco , Técnicas In Vitro , Exposição Ambiental/análise
17.
J Adv Res ; 48: 61-74, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36041690

RESUMO

INTRODUCTION: Reducing the protein adsorption of nanoparticles (NPs) as drug carriers to slow their rapid clearance by macrophages uptake is a critical challenge for NPs clinical translational applications. Despite extensive research efforts to inhibit cellular uptake, including covering biological agents or surface chemical coatings to impart "stealth" properties to NPs, their stability remains insufficient. OBJECTIVES: Developed a novel surface modification technology based on a physical infusion engineering approach to achieve persistent inhibition of protein adhesion and cellular uptake by nanocarriers. METHODS: The nanoparticles were prepared based on conventional drug carrier mesoporous silica NPs through a two-step process. A functional nanoscale slippery surface was formed by grafting "liquid-like" brushes on the particles surface, and then a lubricant-entrenched slippery surfaces (LESS) was formed by infusing silicone oil lubricant into the entire surface. Co-incubation with macrophages (in vitro and in vivo) was used to examine the anti-uptake properties of modified NPs. The anti-adhesion properties of LESS coating surfaces to various liquids, proteins and cells were used to analyze the anti-uptake mechanism. Loaded with drugs, combined with tumor models, to evaluate the drug utilization of modified NPs. RESULTS: Relying on the stable and slippery LESS coating, the modified surface could prevent the adhesion of various liquids and effectively shield against the adhesion of proteins and cells, as well as remarkably reduce macrophage cellular uptake in vitro and in vivo. In addition, the LESS coating does not affect cell activity and allows NPs to be loaded with drugs, significantly improving the utilization of drugs in vitro and in vivo. This allows the NPs to reach to the target tumor site for drug delivery without active clearance by macrophages. CONCLUSION: Our research introduces a new nanocarrier technology to improve anti-biofouling performance and stealth efficiency that will facilitate the development of nanomedicines for clinical transformation applications.


Assuntos
Macrófagos , Nanopartículas , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/química , Nanopartículas/química , Uso de Medicamentos
18.
J Food Biochem ; 46(12): e14503, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36331088

RESUMO

Chrysanthemum morifolium is a well-known edible medicinal plant in Asia and some other regions. Content of selenium in Se-enriched C. morifolium (SeCM) is significantly higher than that in traditional C. morifolium (non-Se-enriched C. morifolium, TCM). In order to understand health effects of SeCM, its chemical composition, lifespan-prolonging activities, and impacts on antioxidant defense-related gene expressions of model organism D. melanogaster were systematically studied. A total of eight phenols, including luteolin-7-O-glucoside, linarin, luteolin, apigenin, diosmetin, acacetin, 3-caffeoylquinic acid and 4,5-dicaffeoylquinic acid, were identified in SeCM extract. Compared with TCM, SeCM exhibited superior antioxidant properties. Intake of SeCM dramatically reduced malondialdehyde level and increased activities of endogenous antioxidant enzymes in fruit flies. SeCM was able to upregulate gene expressions of Cu/Zn-superoxide dismutase, Mn-superoxide dismutase and hydrogen peroxide catalase, and extend lifespans of fruit flies. Comparatively high antioxidant capacities and lifespan-prolonging activities of SeCM might be attributed to its abundant phenols and selenium, which probably ameliorated accumulation of free radicals and susceptibility to oxidative stress. These findings provide clues on further exploitation and utilization of Se-enriched C. morifolium. PRACTICAL APPLICATIONS: Chrysanthemum morifolium has been used for nutraceutical and curative purposes in China for thousands of years. Se-enriched C. morifolium typically contains more selenium than traditional C. morifolium, and is widely consumed in Asia and some other regions. Selenium is an essential micronutrient for humans, and selenium deficiency may result in several diseases such as myocardial infarction. SeCM is one of important selenium supplements. In this study, SeCM was found to upregulate gene expressions of Cu/Zn-superoxide dismutase, Mn-superoxide dismutase, and hydrogen peroxide catalase, and extend lifespans of experimental animals. These results provide supporting information for developing SeCM-based functional foods with distinct health benefits.


Assuntos
Chrysanthemum , Selênio , Humanos , Animais , Antioxidantes/farmacologia , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Catalase/genética , Catalase/metabolismo , Selênio/farmacologia , Longevidade , Chrysanthemum/genética , Chrysanthemum/química , Chrysanthemum/metabolismo , Peróxido de Hidrogênio , Superóxidos , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Fenóis , Expressão Gênica
19.
Phys Med ; 100: 81-89, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35759943

RESUMO

PURPOSE: Interstitial needles placement is a critical component of combined intracavitary/interstitial (IC/IS) brachytherapy (BT). To ensure precise placement of interstitial needles, we proposed a novel ultrasonic (US) probe calibration method to accurately register the US image in the magnetic resonance imaging (MRI) image and provide multimodal image guidance for needle placement. METHODS: A wire-based calibration phantom combined with the stylus was developed for the calibration of US probe. The calibration phantom helps to quickly align the imaging plane of the US probe with the fiducial points to obtain US images of these points. The coordinates of fiducial points in US images were located automatically by feature extraction algorithms and were further corrected by the proposed correction method. Ingenious structures were designed on both sides of the calibration phantom to accurately obtain the coordinates of the fiducial points relative to the tracking device. Marker validation and pelvic phantom study were performed to evaluate the accuracy of the proposed calibration method. RESULTS: In the marker validation, the US probe calibration method with corrected transformation achieves a registration accuracy of 0.694 ± 0.014 mm, and the uncorrected one is 0.746 ± 0.018 mm. In the pelvic phantom study, the needle tip difference was 1.096 ± 0.225 mm and trajectory difference was 1.416 ± 0.284 degrees. CONCLUSION: The proposed US probe calibration method is helpful to achieve more accurate multimodality image guidance for needle placement.


Assuntos
Braquiterapia , Neoplasias do Colo do Útero , Braquiterapia/métodos , Calibragem , Feminino , Humanos , Agulhas , Imagens de Fantasmas , Ultrassonografia , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/radioterapia
20.
J Pharm Pharmacol ; 74(8): 1061-1084, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35723937

RESUMO

OBJECTIVES: Croton tiglium Linn. (Euphorbiaceae) is an ancient medicinal plant that has been used for a long time, which is widely distributed in tropical and subtropical regions. And it is widely used for defecation, induced labour, treatment of gastrointestinal diseases, headache, as well as rheumatoid arthritis. KEY FINDINGS: Approximately 150 compounds have been isolated and identified from the seeds, stems, leaves and branches of C. tiglium, including fatty acids, terpenoids, alkaloids, the plants proteins and other types of components. Based on a wide range of biological properties, C. tiglium has a wide range of pharmacological effects, such as antitumor, anti-HIV, analgesic, anti-inflammatory and antibacterial effects. SUMMARY: The review aims to provide a critical and comprehensive evaluation of the botany, phytochemistry, pharmacology and toxicity of C. tiglium, with a vision for promoting further pharmaceutical research to explore its complete potential for better clinical application. The tigliane diterpenoids have been the most studied compounds isolated from C. tiglium, which showing a variety of biological activities, but there is insufficient evidence to explain the mechanism of action. In addition, C. tiglium may have potential toxic effects, and it is necessary to reduce the toxic effects to ensure the safety of clinical medication, which may promote the discovery and development of new drugs.


Assuntos
Botânica , Croton , Croton/química , Etnobotânica , Etnofarmacologia , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Folhas de Planta
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