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1.
Adv Healthc Mater ; 13(13): e2303674, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38315148

RESUMO

Intrauterine adhesion (IUA) stands as a prevalent medical condition characterized by endometrial fibrosis and scar tissue formation within the uterine cavity, resulting in infertility and, in severe cases, recurrent miscarriages. Cell therapy, especially with stem cells, offers an alternative to surgery, but concerns about uncontrolled differentiation and tumorigenicity limit its use. Exosomes, more stable and immunogenicity-reduced than parent cells, have emerged as a promising avenue for IUA treatment. In this study, a novel approach has been proposed wherein exosomes originating from decidual stromal cells (DSCs) are encapsulated within sodium alginate hydrogel (SAH) scaffolds to repair endometrial damage and restore fertility in a mouse IUA model. Current results demonstrate that in situ injection of DSC-derived exosomes (DSC-exos)/SAH into the uterine cavity has the capability to induce uterine angiogenesis, initiate mesenchymal-to-epithelial transformation (MET), facilitate collagen fiber remodeling and dissolution, promote endometrial regeneration, enhance endometrial receptivity, and contribute to the recovery of fertility. RNA sequencing and advanced bioinformatics analysis reveal miRNA enrichment in exosomes, potentially supporting endometrial repair. This finding elucidates how DSC-exos/SAH mechanistically fosters collagen ablation, endometrium regeneration, and fertility recovery, holding the potential to introduce a novel IUA treatment and offering invaluable insights into the realm of regenerative medicine.


Assuntos
Alginatos , Endométrio , Exossomos , Hidrogéis , Regeneração , Células Estromais , Feminino , Alginatos/química , Exossomos/metabolismo , Exossomos/química , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Endométrio/citologia , Endométrio/metabolismo , Camundongos , Regeneração/efeitos dos fármacos , Células Estromais/metabolismo , Células Estromais/citologia , Decídua/citologia , Decídua/metabolismo , Fertilidade/fisiologia , MicroRNAs/metabolismo , MicroRNAs/genética , Humanos , Aderências Teciduais/metabolismo
2.
Sci Adv ; 10(1): eadj1741, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38170782

RESUMO

Bacteria can swim upstream in a narrow tube and pose a clinical threat of urinary tract infection to patients implanted with catheters. Coatings and structured surfaces have been proposed to repel bacteria, but no such approach thoroughly addresses the contamination problem in catheters. Here, on the basis of the physical mechanism of upstream swimming, we propose a novel geometric design, optimized by an artificial intelligence model. Using Escherichia coli, we demonstrate the anti-infection mechanism in microfluidic experiments and evaluate the effectiveness of the design in three-dimensionally printed prototype catheters under clinical flow rates. Our catheter design shows that one to two orders of magnitude improved suppression of bacterial contamination at the upstream end, potentially prolonging the in-dwelling time for catheter use and reducing the overall risk of catheter-associated urinary tract infection.


Assuntos
Cateteres Urinários , Infecções Urinárias , Humanos , Cateteres Urinários/microbiologia , Inteligência Artificial , Infecções Urinárias/prevenção & controle , Infecções Urinárias/microbiologia , Bactérias , Escherichia coli , Hidrolases
3.
Soft Matter ; 20(5): 1100-1113, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38221884

RESUMO

Self-propelled colloidal particles exhibit rich non-equilibrium phenomena and have promising applications in fields such as drug delivery and self-assembled active materials. Previous experimental and theoretical studies have shown that chemically active colloids that consume or produce a chemical can self-organize into clusters with diverse characteristics depending on the effective phoretic interactions. In this paper, we investigate self-organization in systems with multiple chemical species that undergo a network of reactions and multiple colloidal species that participate in different reactions. Active colloids propelled by complex chemical reactions with potentially nonlinear kinetics can be realized using enzymatic reactions that occur on the surface of enzyme-coated particles. To demonstrate how the self-organizing behavior depends on the chemical reactions active colloids catalyze and their chemical environment, we consider first a single type of colloid undergoing a simple catalytic reaction, and compare this often-studied case with self-organization in binary mixtures of colloids with sequential reactions, and binary mixtures with nonlinear autocatalytic reactions. Our results show that in general active colloids at low particle densities can form localized clusters in the presence of bulk chemical reactions and phoretic attractions. The characteristics of the clusters, however, depend on the reaction kinetics in the bulk and on the particles and phoretic coefficients. With one or two chemical species that only undergo surface reactions, the space for possible self-organizations are limited. By considering the additional system parameters that enter the chemical reaction network involving reactions on the colloids and in the fluid, the design space of colloidal self-organization can be enlarged, leading to a variety of non-equilibrium structures.

4.
Acad Radiol ; 31(4): 1615-1628, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37949702

RESUMO

RATIONALE AND OBJECTIVES: This study aims to evaluate the feasibility and effectiveness of deep transfer learning (DTL) and clinical-radiomics in differentiating thymoma from thymic cysts. MATERIALS AND METHODS: Clinical and imaging data of 196 patients pathologically diagnosed with thymoma and thymic cysts were retrospectively collected from center 1. (training cohort: n = 137; internal validation cohort: n = 59). An independent external validation cohort comprised 68 thymoma and thymic cyst patients from center 2. Region of interest (ROI) delineation was performed on contrast-enhanced chest computed tomography (CT) images, and eight DTL models including Densenet 169, Mobilenet V2, Resnet 101, Resnet 18, Resnet 34, Resnet 50, Vgg 13, Vgg 16 were constructed. Radiomics features were extracted from the ROI on the CT images of thymoma and thymic cyst patients, and feature selection was performed using intra-observer correlation coefficient (ICC), Spearman correlation analysis, and least absolute shrinkage and selection operator (LASSO) algorithm. Univariate analysis and multivariable logistic regression (LR) were used to select clinical-radiological features. Six machine learning classifiers, including LR, support vector machine (SVM), k-nearest neighbors (KNN), Light Gradient Boosting Machine (LightGBM), Adaptive Boosting (AdaBoost), and Multilayer Perceptron (MLP), were used to construct Radiomics and Clinico-radiologic models. The selected features from the Radiomics and Clinico-radiologic models were fused to build a Combined model. Receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, calibration, and clinical utility of the models, respectively. The Delong test was used to compare the AUC between different models. K-means clustering was used to subdivide the lesions of thymomas or thymic cysts into subregions, and traditional radiomics methods were used to extract features and compare the ability of Radiomics and DTL models to reflect intratumoral heterogeneity using correlation analysis. RESULTS: The Densenet 169 based on DTL performed the best, with AUC of 0.933 (95% CI: 0.875-0.991) in the internal validation cohort and 0.962 (95% CI: 0.923-1.000) in the external validation cohort. The AdaBoost classifier achieved AUC of 0.965 (95% CI: 0.923-1.000) and 0.959 (95% CI: 0.919-1.000) in the internal and external validation cohorts, respectively, for the Radiomics model. The LightGBM classifier achieved AUC of 0.805 (95% CI: 0.690-0.920) and 0.839 (95% CI: 0.736-0.943) in the Clinico-radiologic model. The AUC of the Combined model in the internal and external validation cohorts was 0.933 (95% CI: 0.866-1.000) and 0.945 (95% CI: 0.897-0.994), respectively. The results of the Delong test showed that the Radiomics model, DTL model, and Combined model outperformed the Clinico-radiologic model in both internal and external validation cohorts (p-values were 0.002, 0.004, and 0.033 in the internal validation cohort, while in the external validation cohort, the p-values were 0.014, 0.006, and 0.015, respectively). But there was no statistical difference in performance among the three models (all p-values <0.05). Correlation analysis showed that radiomics performed better than DTL in quantifying intratumoral heterogeneity differences between thymoma and thymic cysts. CONCLUSION: The developed DTL model and the Combined model based on radiomics and clinical-radiologic features achieved excellent diagnostic performance in differentiating thymic cysts from thymoma. They can serve as potential tools to assist clinical decision-making, particularly when endoscopic biopsy carries a high risk.


Assuntos
Cisto Mediastínico , Timoma , Neoplasias do Timo , Humanos , Radiômica , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Aprendizado de Máquina , Neoplasias do Timo/diagnóstico por imagem
5.
J Pediatr Urol ; 20(1): 147-148, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37806833

RESUMO

INTRODUCTION: To report a novel maneuver of end-to-side urethro-urethrostomy for managing Type IIA1 urethral duplication (UD). MATERIALS AND METHODS: A 3-years-old boy was referred to our institute for abnormal appearance of genitalia. Physical examination revealed an epispadiac meatus on the dorsum of the penile shaft, in addition to the orthotopic meatus at the tip of glans. He can void through both urethrae with continence (grade I). Voiding cystourethrography and the cystoscopy confirmed the Type IIA1 UD with two urethrae arising independently from the bladder neck. A novel maneuver of end-to-side urethro-urethrostomy transferring the dorsal urethra through the corpus cavernosa and anastomosing it to the posterior wall of the ventral urethra was successfully performed. RESULTS: The urethral catheter was removed 2 weeks postoperatively. Neither urethral stricture nor fistula was noticed. After 1 year of followed-up, the boy can void fluently with continence (grade I). The Qmax was 10.4 ml/s. CONCLUSION: Our maneuver of end-to-side urethro-urethrostomy for managing Type IIA1 UD was safe and effective, especially for the continent cases with the ectopic meatus on the penile shaft.


Assuntos
Epispadia , Estreitamento Uretral , Masculino , Humanos , Pré-Escolar , Uretra/diagnóstico por imagem , Uretra/cirurgia , Procedimentos Cirúrgicos Urológicos , Epispadia/cirurgia , Pênis/cirurgia
6.
Hum Cell ; 37(1): 85-100, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37751026

RESUMO

In recent years, with the continuous in-depth exploration of the molecular mechanisms of tumorigenesis, numerous potential new targets for cancer treatment have been identified, some of which have been further developed in clinical practice and have produced positive outcomes. Notably, researchers' initial motivation for studying copper metabolism in cancer stems from the fact that copper is a necessary trace element for organisms and is closely connected to body growth and metabolism. Moreover, over the past few decades, considerable progress has been made in understanding the molecular processes and correlations between copper and cancer. Certain achievements have been made in the development and use of relevant clinical medications. The concept of "cuproptosis," a novel concept that differs from previous forms of cell death, was first proposed by a group of scientists last year, offering fresh perspectives on the targeting capabilities of copper in the treatment of cancer. In this review, we introduced the fundamental physiological functions of copper, the key components of copper metabolism, and a summary of the current research contributions on the connection between copper and cancer. In addition, the development of new copper-based nanomaterials and their associated mechanisms of action are discussed. Finally, we described how the susceptibility of cancer cells to this metallic nutrition could be leveraged to further improve the existing cancer treatment paradigm in the new setting.


Assuntos
Cobre , Neoplasias , Humanos , Cobre/metabolismo , Cobre/uso terapêutico , Neoplasias/tratamento farmacológico , Carcinogênese
7.
Biomater Sci ; 12(1): 92-107, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-37965798

RESUMO

Titanium (Ti) and its alloys are widely used in clinical practice. As they are not bioactive, hydroxyapatite (HA) is commonly used to modify them. This study offered a review of microwave-assisted synthesis of composites based on Ti and HA for dental implantation by exploring their interaction mechanisms with microwave and features of two main techniques, namely microwave coating and sintering, along with current challenges and potential solutions in the field. It was shown that microwave coating enables rapid deposition of HA, but suffers from problems such as uneven coating thickness, poor integrity and unstable composition of the products. They can be solved by creating interlayers, combining the spin coating technique, etc. Unlike microwave coating, microwave sintering can effectively modify the mechanical properties of the composites, despite the shortcomings of excessive elastic moduli and potential HA decomposition. These issues are expected to be addressed by adding alloying elements and employing appropriate materials as space holders and ion-doped HA for sintering.


Assuntos
Durapatita , Titânio , Micro-Ondas , Propriedades de Superfície , Teste de Materiais , Ligas , Implantação Dentária , Materiais Revestidos Biocompatíveis
8.
Int J Biol Macromol ; 253(Pt 6): 127314, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37827397

RESUMO

A thinner endometrium has been linked to implantation failure, and various therapeutic strategies have been attempted to improve endometrial regeneration, including the use of mesenchymal stem cells (MSCs). However, low survival and retention rates of transplanted stem cells are main obstacles to efficient stem cell therapy in thin endometrium. Collagen type III is a key component of the extracellular matrix, plays a crucial role in promoting cell proliferation and differentiation, and has been identified as the major collagen expressed at the implantation site. Herein, composite alginate hydrogel containing recombinant type III collagen (rCo III) and umbilical cord mesenchymal stem cells are developed. rCo III serves as favorable bioactive molecule, displaying that rCo III administration promotes MSCs proliferation, stemness maintenance and migration. Moreover, rCo III administration enhances cell viability and migration of mouse endometrial stromal cells (ESCs). In a mouse model of thin endometrium, the Alg-rCo III hydrogel loaded with MSCs (MSC/Alg-rCo III) significantly induces endometrial regeneration and fertility enhancement in vivo. Further studies demonstrate that the MSC/Alg-rCo III hydrogel promoted endometrial function recovery partly by regulating mesenchymal-epithelial transition of ESCs. Taken together, the combination of Alg-rCo III hydrogel and MSCs has shown promising results in promoting endometrium regeneration and fertility restoration, and may provide new therapeutic options for endometrial disease.


Assuntos
Colágeno Tipo III , Células-Tronco Mesenquimais , Feminino , Camundongos , Animais , Colágeno Tipo III/metabolismo , Hidrogéis/farmacologia , Hidrogéis/metabolismo , Alginatos/farmacologia , Alginatos/metabolismo , Endométrio , Fertilidade/fisiologia
9.
Front Bioeng Biotechnol ; 11: 1222088, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37539434

RESUMO

The development of cost-effective, biocompatible soft wound dressings is highly desirable; however, conventional dressings are only designed for flat wounds, which creates difficulty with promising healing efficiency in complex practical conditions. Herein, we developed a tough, adhesive biomimetic hyaluronic acid methacryloyl hydrogels composed of chemically crosslinked hyaluronic acid methacryloyl (HAMA) network and poly(N-hydroxyethyl acrylamide) (PHEAA) network rich in multiple hydrogen bonding. Due to the multiple chemical crosslinking sites (acrylamide groups) of HAMA; the bulk HEMA/PHEAA hydrogels presented significant enhancements in mechanical properties (∼0.45 MPa) than common hyaluronic acid hydrogels (<0.1 MPa). The abundant hydrogen bonding also endowed the resultant hydrogels with extremely high adhesiveness on many nonporous substrates, including glass and biological tissues (e.g., heart, liver, lung, kidney, stomach, and muscle), with a considerable interfacial toughness of ∼1432 J m-2. Accordingly, since both natural hyaluronic acid derivative polymers and hydrophilic PHEAA networks are highly biocompatible, the hydrogel matrix possesses good blood compatibility (<5% of hemolysis ratio) and satisfies the general dressing requirements (>99% of cell viability). Based on these physicochemical features, we have demonstrated that this adhesive hydrogel, administered in the form of a designed patch, could be applied to wound tissue healing by promoting epithelialization, angiogenesis, and collagen deposition. We believe that our proposed biomimetic hydrogel design holds great potential for wound repair and our developed HAMA/PHEAA hydrogels are extremely promising for the next-generation tissue healings in emergency situations.

10.
BMC Biotechnol ; 23(1): 29, 2023 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-37587435

RESUMO

BACKGROUND: Porcine fetal fibroblasts (PFFs) are important donor cells for generating genetically modified pigs, but the transfection efficiencies of PFFs are often unsatisfactory especially when large-size vectors are to be delivered. In this study, we aimed to optimize the transfection conditions for delivery of a large-size vector in PFFs using Lonza 4D-Nucleofector™ vessels and strips. METHODS: We firstly delivered a 13 kb Cas9-EGFP and a 3.5 kb pMAX-GFP vector into PFFs via 7 programs recommended by the Lonza basic protocol. We then tested 6 customized dual-electroporation programs for delivering the 13 kb plasmid into PFFs. In addition, we screened potential alternative electroporation buffers to the Nucleofector™ P3 solution. Finally, three CRISPR/Cas9-sgRNAs targeting Rosa26, H11, and Cep112 loci were delivered into PFFs with different single and dual-electroporation programs. RESULTS: Notably lower transfection efficiencies were observed when delivering the 13 kb vector than delivering the 3.5 kb vector in PFFs via the single-electroporation programs. The customized dual-electroporation program FF-113 + CA-137 exhibited higher transfection efficiencies than any of the single-electroporation programs using vessels (98.1%) or strips (89.1%) with acceptable survival rates for the 13 kb vector. Entranster-E buffer generated similar transfection efficiencies and 24-hour survival rates to those from the P3 solution, thus can be used as an alternative electroporation buffer. In the genome-editing experiments, the FF-113 + CA-137 and CA-137 + CA-137 programs showed significantly superior (P < 0.01) efficiencies to ones from the single-electroporation programs in vessels and strips. Entranster-E buffer produced higher indel efficiencies than the P3 buffer. CONCLUSIONS: We markedly increased the delivery efficiencies for a large vector via customized dual-electroporation programs using Lonza 4D-Nucleofector™ system, and Entranster-E buffer can be used as an alternative electroporation buffer to Nucleofector™ P3 buffer.


Assuntos
Sistemas CRISPR-Cas , RNA Guia de Sistemas CRISPR-Cas , Suínos , Animais , Feto , Eletroporação , Fibroblastos
11.
Sci Rep ; 13(1): 12896, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37558719

RESUMO

Joshimath has received much attention for its massive ground subsidence at the beginning of the year. Rapid urbanization and its unique geographical location may have been one of the factors contributing to the occurrence of this geological disaster. In high mountain valley areas, the complex occurrence mechanism and diverse disaster patterns of geological hazards highlight the inadequacy of manual monitoring. To address this problem, the inversion of deformation of the Joshimath surface in multiple directions can be achieved by multidimensional InSAR techniques. Therefore, in this paper, the multidimensional SBAS-InSAR technique was used to process the lift-track Sentinel-1 data from 2020 to 2023 to obtain the two-dimensional vertical and horizontal deformation rates and time series characteristics of the Joshimath ground surface. To discover the causes of deformation and its correlation with anthropogenic activities and natural disasters by analyzing the spatial and temporal evolution of surface deformation. The results show that the area with the largest cumulative deformation is located in the northeastern part of the town, with a maximum cumulative subsidence of 271.2 mm and a cumulative horizontal movement of 336.5 mm. The spatial distribution of surface deformation is based on the lower part of the hill and develops towards the upper part of the hill, showing a trend of expansion from the bottom to the top. The temporal evolution is divided into two phases: gentle to rapid, and it is tentatively concluded that the decisive factor that caused the significant change in the rate of surface deformation and the early onset of the geological subsidence hazard was triggered by the 4.7 magnitude earthquake that struck near the town on 11 September 2021.

12.
Int J Mol Sci ; 24(14)2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37511629

RESUMO

Gastric cancer (GC) is the third leading cause of cancer-related death worldwide. Due to the lack of early symptoms, GC is often diagnosed at an advanced stage when treatment options are limited. There is an urgent need to identify biomarkers for early detection, prognosis evaluation, and targeted treatment of GC. Studies have shown that Src kinase-associated phosphoprotein 1 (SKAP1) promotes cell proliferation and invasion and is associated with poor prognosis in colorectal cancer, malignant fibrous histiocytoma, and breast cancer. However, the role and mechanism of SKAP1 in GC are unclear. Here, analyses of multiple databases and experiments revealed that SKAP1 expression was higher in GC than in adjacent normal tissues. The Cancer Genome Atlas data showed that high SKAP1 expression was associated with poor GC prognosis. SKAP1 expression was higher in GC than in normal gastric epithelial cells. SKAP1 silencing reduced the proliferation, migration and invasion of the GC cell lines MKN45 and HGC27. Rescue experiments suggest that SKAP1 may promote GC progression by activating JAK1/PI3K/AKT signaling and regulating GC cell proliferation, invasion, migration, and other functions. Bioinformatics analysis revealed that SKAP1 was associated with immune cell infiltration and checkpoint expression in GC. High SKAP1 expression was associated with poorer immunotherapy outcomes, suggesting its potential as a predictive biomarker of GC immunotherapy efficacy. In summary, SKAP1 is overexpressed in GC, where it promotes cell proliferation, invasion and migration and is associated with poor prognosis and poor immunotherapy outcomes. SKAP1 may represent a biomarker and therapeutic target in GC and regulates cellular functions through JAK1/PI3K/AKT signaling.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Neoplasias Gástricas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Movimento Celular/genética , Proliferação de Células/genética , Biomarcadores , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Fosfoproteínas/metabolismo
13.
J Transl Med ; 21(1): 405, 2023 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-37344903

RESUMO

BACKGROUND: The therapeutic targeting of the tumor microenvironment (TME) in colorectal cancer (CRC) has not yet been fully developed and utilized because of the complexity of the cell-cell interactions within the TME. The further exploration of these interactions among tumor-specific clusters would provide more detailed information about these communication networks with potential curative value. METHODS: Single-cell RNA sequencing, spatial transcriptomics, and bulk RNA sequencing datasets were integrated in this study to explore the biological properties of MFAP5 + fibroblasts and their interactions with tumor-infiltrating myeloid cells in colorectal cancer. Immunohistochemistry and multiplex immunohistochemistry were performed to confirm the results of these analyses. RESULTS: We profiled heterogeneous single-cell landscapes across 27,414 cells obtained from tumors and adjacent tissues. We mainly focused on the pro-tumorigenic functions of the identified MFAP5 + fibroblasts. We demonstrated that tumor-resident MFAP5 + fibroblasts and myeloid cells (particularly C1QC + macrophages) were positively correlated in both spatial transcriptomics and bulk RNA-seq public cohorts. These cells and their interactions might shape the malignant behavior of CRC. Intercellular interaction analysis suggested that MFAP5 + fibroblasts could reciprocally communicate with C1QC + macrophages and other myeloid cells to remodel unfavorable conditions via MIF/CD74, IL34/CSF1R, and other tumor-promoting signaling pathways. CONCLUSION: Our study has elucidated the underlying pro-tumor mechanisms of tumor-resident MFAP5 + fibroblasts and provided valuable targets for the disruption of their properties.


Assuntos
Neoplasias Colorretais , Peptídeos e Proteínas de Sinalização Intercelular , Humanos , Transdução de Sinais , Células Mieloides/patologia , Fibroblastos/patologia , Neoplasias Colorretais/genética , Microambiente Tumoral/genética
14.
Mol Med ; 29(1): 66, 2023 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-37217855

RESUMO

Cancer-associated fibroblasts (CAFs) are the most abundant stromal cells within the tumor microenvironment (TME). They extensively communicate with the other cells. Exosome-packed bioactive molecules derived from CAFs can reshape the TME by interacting with other cells and the extracellular matrix, which adds a new perspective for their clinical application in tumor targeted therapy. An in-depth understanding of the biological characteristics of CAF-derived exosomes (CDEs) is critical for depicting the detailed landscape of the TME and developing tailored therapeutic strategies for cancer treatment. In this review, we have summarized the functional roles of CAFs in the TME, particularly focusing on the extensive communication mediated by CDEs that contain biological molecules such as miRNAs, proteins, metabolites, and other components. In addition, we have also highlighted the prospects for diagnostic and therapeutic applications based on CDEs, which could guide the future development of exosome-targeted anti-tumor drugs.


Assuntos
Fibroblastos Associados a Câncer , Exossomos , MicroRNAs , Neoplasias , Humanos , Exossomos/metabolismo , Microambiente Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/metabolismo , Linhagem Celular Tumoral , Fibroblastos/metabolismo
15.
Gels ; 9(4)2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37102913

RESUMO

Osteoporosis is one of the most disabling consequences of aging, and osteoporotic fractures and a higher risk of subsequent fractures lead to substantial disability and deaths, indicating that both local fracture healing and early anti-osteoporosis therapy are of great significance. However, combining simple clinically approved materials to achieve good injection and subsequent molding and provide good mechanical support remains a challenge. To meet this challenge, bioinspired by natural bone components, we develop appropriate interactions between inorganic biological scaffolds and organic osteogenic molecules, achieving a tough hydrogel that is both firmly loaded with calcium phosphate cement (CPC) and injectable. Here, the inorganic component CPC composed of biomimetic bone composition and the organic precursor, incorporating gelatin methacryloyl (GelMA) and N-Hydroxyethyl acrylamide (HEAA), endow the system with fast polymerization and crosslinking through ultraviolet (UV) photo-initiation. The GelMA-poly (N-Hydroxyethyl acrylamide) (GelMA-PHEAA) chemical and physical network formed in situ enhances the mechanical performances and maintains the bioactive characteristics of CPC. This tough biomimetic hydrogel combined with bioactive CPC is a new promising candidate for a commercial clinical material to help patients to survive osteoporotic fracture.

16.
Pathol Res Pract ; 245: 154461, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37060821

RESUMO

This study explored the connection between KDM6A expression and patient prognosis and the mechanism of KDM6A's role in developing GC (GC). From the immunohistochemical Analysis of 107 GC patients' tumors, we discovered that patients with reduced KDM6A expression had a shorter survival time. There was a correlation between KDM6A expression and the degree of differentiation of tumor tissue, T stage, N stage, and TNM stage. KDM6A gene expression was positively connected with the expression level of E-cadherin and negatively connected with the expression level of N-cadherin and vimentin in vitro tests. KDM6A gene suppression prevented GC cell proliferation, migration, and invasion, whereas high KDM6A gene expression promoted these processes. Second, low expression of KDM6A down-regulates GSK3ß, p-GSK3ß, up-regulates C-Myc, CyclinD1, and promotes ß-catenin protein expression in the nucleus, while the high expression does the opposite. Then, we used ICG001 to block the Wnt/ß-catenin signal transduction pathway, and the results revealed that ICG001 could reduce the promoting effect of low KDM6A expression on aggressiveness and EMT in GC cells. KDM6A down-regulation stimulates the proliferation of GC cells, while ICG001 reverses this action in vivo tests. Patients whose KDM6A expression was found to be low had a poor prognosis, as this study found. The EMT is inhibited by regulating theWnt/ß-catenin signaling by KDM6A, which reduces GC cell proliferation, migration, and invasion. KDM6A may be a viable target for GC in clinical therapy.


Assuntos
Neoplasias Gástricas , beta Catenina , Humanos , beta Catenina/metabolismo , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/metabolismo , Neoplasias Gástricas/patologia , Via de Sinalização Wnt/genética
17.
World J Urol ; 41(3): 813-819, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36745192

RESUMO

PURPOSE: This study aimed to compare the efficacy of modified transverse preputial island flap (TPIF) repair with the traditional TPIF procedure and Byar's two-stage procedure in proximal hypospadias repair, especially in the postoperative urethral stricture incidence rates. MATERIALS AND METHODS: Patients admitted for proximal hypospadias treated with modified TPIF repair, the traditional TPIF procedure, or Byar's two-stage procedure at our institution from 2017 to 2021 were identified, and the incidence of postoperative complications among them was compared. RESULTS: In total, 142 patients were included (modified TPIF group, 43; traditional TPIF group, 37; and Byar's two-stage group, 62). The length of the neourethra was 4.21 ± 0.63 cm in the modified TPIF group, 4.18 ± 0.71 cm in the traditional TPIF group, and 4.20 ± 0.68 cm in the Byar's two-stage group. The rate of urethral stricture in the modified TPIF group (two cases, 4.65%) was significantly lower than that in the traditional TPIF group (four cases, 10.81%) (P = 0.008). Seven (16.28%) cases of urethrocutaneous fistula occurred in the modified TPIF group, six (16.22%) in the traditional TPIF group, and eight (12.90%) in the two-stage group. Additionally, one case (2.33%) of urethral diverticulum occurred in the modified TPIF group, one (2.70%) in the traditional TPIF group, and three (4.84%) in Byar's two-stage group. CONCLUSIONS: Modified TPIF repair can ensure a wedge anastomosis between the proximal urethral meatus and the neourethra, provide support and blood supply for the neourethra. Furthermore, it extended the urethral plate width at the anastomosis and urethral meatus, effectively reducing the incidence of urethral strictures.


Assuntos
Hipospadia , Procedimentos de Cirurgia Plástica , Estreitamento Uretral , Masculino , Humanos , Lactente , Hipospadia/cirurgia , Estreitamento Uretral/epidemiologia , Estreitamento Uretral/cirurgia , Retalhos Cirúrgicos , Uretra/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Procedimentos Cirúrgicos Urológicos Masculinos/métodos
18.
Soft Matter ; 19(7): 1384-1392, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36723138

RESUMO

We analyze a dilute suspension of active particles confined between walls and subjected to fields that can modulate particle speed as well as orientation. Generally, the particle distribution is different in the bulk compared to near the walls. In the bulk, particles tend to accumulate in the regions of low speed, but in the presence of an orienting field normal to the walls, particles rotate to align with the field and accumulate in the field direction. At the walls, particles tend to accumulate pointing into the walls and thereby exert pressure on walls. But the presence of strong orienting fields can cause the particles to reorient away from the walls, and hence shows a possible mechanism for preventing contamination of surfaces. The pressure at the walls depends on the wall separation and the field strengths. This work demonstrates how multiple fields with different functionalities can be used to control active matter under confinement.

19.
Front Oncol ; 12: 949111, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505773

RESUMO

Objective: Based on pretherapy dual-energy computed tomography (DECT) images, we developed and validated a nomogram combined with clinical parameters and radiomic features to predict the pathologic subtypes of non-small cell lung cancer (NSCLC) - adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Methods: A total of 129 pathologically confirmed NSCLC patients treated at the Second Affiliated Hospital of Nanchang University from October 2017 to October 2021 were retrospectively analyzed. Patients were randomly divided in a ratio of 7:3 (n=90) into training and validation cohorts (n=39). Patients' pretherapy clinical parameters were recorded. Radiomics features of the primary lesion were extracted from two sets of monoenergetic images (40 keV and 100 keV) in arterial phases (AP) and venous phases (VP). Features were selected successively through the intra-class correlation coefficient (ICC) and the least absolute shrinkage and selection operator (LASSO). Multivariate logistic regression analysis was then performed to establish predictive models. The prediction performance between models was evaluated and compared using the receiver operating characteristic (ROC) curve, DeLong test, and Akaike information criterion (AIC). A nomogram was developed based on the model with the best predictive performance to evaluate its calibration and clinical utility. Results: A total of 87 ADC and 42 SCC patients were enrolled in this study. Among the five constructed models, the integrative model (AUC: Model 4 = 0.92, Model 5 = 0.93) combining clinical parameters and radiomic features had a higher AUC than the individual clinical models or radiomic models (AUC: Model 1 = 0.84, Model 2 = 0.79, Model 3 = 0.84). The combined clinical-venous phase radiomics model had the best predictive performance, goodness of fit, and parsimony; the area under the ROC curve (AUC) of the training and validation cohorts was 0.93 and 0.90, respectively, and the AIC value was 60.16. Then, this model was visualized as a nomogram. The calibration curves demonstrated it's good calibration, and decision curve analysis (DCA) proved its clinical utility. Conclusion: The combined clinical-radiomics model based on pretherapy DECT showed good performance in distinguishing ADC and SCC of the lung. The nomogram constructed based on the best-performing combined clinical-venous phase radiomics model provides a relatively accurate, convenient and noninvasive method for predicting the pathological subtypes of ADC and SCC in NSCLC.

20.
Cancer Manag Res ; 14: 3437-3448, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36536823

RESUMO

Objective: To develop and validate models for predicting distant metastases in patients with solid lung adenocarcinomas using 3D radiomic features, 2D radiomic features, clinical features, and their combinations. Methods: This retrospective study included 253 eligible patients with solid adenocarcinoma of the lung diagnosed at our hospital between August 2018 and August 2021. 3D and 2D regions of interest were segmented from computed tomography-enhanced thin-slice images of the venous phase, and 851 radiomic features were extracted in each region. The Least Absolute Shrinkage and Selection Operator (LASSO) algorithm was used to select radiomic features and calculate radiomic scores, and logistic regression was used to develop the model. Development of a 3D radiomics model (model 1), a 2D radiomics model (model 2), a combined 3D radiomics and 2D radiomics model (model 3), a clinical model (model 4), and a comprehensive model (model 5) for the prediction of distant metastases in patients with solid lung adenocarcinomas. Nomograms were drawn to illustrate model 5, and receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used for model evaluation. Results: The AUC (area under the curve) of model 1, model 2, model 3, model 4, and model 5 in the test set was 0.711, 0.769, 0.775, 0.829, and 0.892, respectively. The Delong test showed that AUC values were statistically different between model 5 and model 1 (p=0.001), and there was no statistical difference in AUC between the other models. Based on a comprehensive review of DCA, ROC curve, and Akaike information criterion (AIC), Model 5 is demonstrated to have better clinical utility, goodness of fit, and parsimony. Conclusion: A comprehensive model based on 3D radiomic features, 2D radiomic features, and clinical features has the potential to predict distant metastasis in patients with solid lung adenocarcinomas.

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