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1.
IEEE Trans Biomed Eng ; PP2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39074001

RESUMO

OBJECTIVE: Multi-color Magnetic Particle Imaging (MPI) technology offers high sensitivity and non-invasive imaging capabilities. It can simultaneously image multiple superparamagnetic iron oxide nanoparticles (SPIOs), facilitating more precise detection of multiple molecular markers in vivo. However, the fixed drive frequency of existing hand-held MPI devices makes it difficult to fully match the nonlinear magnetic response of different SPIOs, affecting the spatial resolution and quantitative accuracy of multi-color imaging. METHODS: We designed a novel rapid frequency conversion based hand-held multi-color magnetic particle imaging (RFC-MPI) device. This device adjusts the drive frequency based on the nonlinear magnetic response of SPIOs at different frequencies, effectively expanding the system matrix information and thereby improving spatial resolution and multi-color imaging capabilities simultaneously. RESULTS: The device achieved a spatial resolution of 2 mm and an imaging speed of 1 frame/s. The scanning depth is 8 mm. It was used to scan a 22 cm x 22 cm area of a human-shaped phantom, verifying its potential for scanning humans. The ability of the device to identify and quantify SPIOs was validated using mice breast tumors. The quantitative accuracy during simultaneous imaging was determined to be 96.58%. CONCLUSION: Due to its innovative structural design and rapid frequency conversion method, the RFC-MPI device exhibits excellent in vivo imaging performance. Both simulation and phantom experiments have verified the effectiveness of the proposed method. SIGNIFICANCE: The hand-held RFC-MPI device can effectively improve the spatial resolution and quantitative accuracy of multi-color MPI, laying the foundation for future clinical applications.

2.
Cell Oncol (Dordr) ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38753155

RESUMO

T lymphocytes are indispensable for the host systems of defense against pathogens, tumors, and environmental threats. The therapeutic potential of harnessing the cytotoxic properties of T lymphocytes for antigen-specific cell elimination is both evident and efficacious. Genetically engineered T-cells, such as those employed in CAR-T and TCR-T cell therapies, have demonstrated significant clinical benefits in treating cancer and autoimmune disorders. However, the current landscape of T-cell genetic engineering is dominated by strategies that necessitate in vitro T-cell isolation and modification, which introduce complexity and prolong the development timeline of T-cell based immunotherapies. This review explores the complexities of gene delivery systems designed for T cells, covering both viral and nonviral vectors. Viral vectors are known for their high transduction efficiency, yet they face significant limitations, such as potential immunogenicity and the complexities involved in large-scale production. Nonviral vectors, conversely, offer a safer profile and the potential for scalable manufacturing, yet they often struggle with lower transduction efficiency. The pursuit of gene delivery systems that can achieve targeted gene transfer to T cell without the need for isolation represents a significant advancement in the field. This review assesses the design principles and current research progress of such systems, highlighting the potential for in vivo gene modification therapies that could revolutionize T-cell based treatments. By providing a comprehensive analysis of these systems, we aim to contribute valuable insights into the future development of T-cell immunotherapy.

3.
Biomacromolecules ; 25(2): 1330-1339, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38254252

RESUMO

The design of imaging agents with a high fluorine content is necessary for overcoming the challenges of low sensitivity in 19F magnetic resonance imaging (MRI)-based molecular imaging. Chemically self-assembled nanorings (CSANs) provide a strategy to increase the fluorine content through multivalent display. We previously reported an 19F NMR-based imaging tracer, in which case a CSAN-compatible epidermal growth factor receptor (EGFR)-targeting protein E1-dimeric dihydrofolate (E1-DD) was bioconjugated to a highly fluorinated peptide. Despite good 19F NMR performance in aqueous solutions, a limited signal was observed in cell-based 19F NMR using this monomeric construct, motivating further design. Here, we design several new E1-DD proteins bioconjugated to peptides of different fluorine contents. Flow cytometry analysis was used to assess the effect of variable fluorinated peptide sequences on the cellular binding characteristics. Structure-optimized protein, RTC-3, displayed an optimal spectral performance with high affinity and specificity for EGFR-overexpressing cells. To further improve the fluorine content, we next engineered monomeric RTC-3 into CSAN, η-RTC-3. With an approximate eightfold increase in the fluorine content, multivalent η-RTC-3 maintained high cellular specificity and optimal 19F NMR spectral behavior. Importantly, the first cell-based 19F NMR spectra of η-RTC-3 were obtained bound to EGFR-expressing A431 cells, showing a significant amplification in the signal. This new design illustrated the potential of multivalent fluorinated CSANs for future 19F MRI molecular imaging applications.


Assuntos
Flúor , Imageamento por Ressonância Magnética , Flúor/química , Espectroscopia de Ressonância Magnética , Proteínas , Peptídeos , Receptores ErbB/metabolismo
4.
Biotechnol Bioeng ; 121(3): 835-852, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38151887

RESUMO

Animal models are routinely employed to assess the treatments for human cancer. However, due to significant differences in genetic backgrounds, traditional animal models are unable to meet bioresearch needs. To overcome this restriction, researchers have generated and optimized immunodeficient mice, and then engrafted human genes, cells, tissues, or organs in mice so that the responses in the model mice could provide a more reliable reference for treatments. As a bridge connecting clinical application and basic research, humanized mice are increasingly used in the preclinical evaluation of cancer treatments, particularly after gene interleukin 2 receptor gamma mutant mice were generated. Human cancer models established in humanized mice support exploration of the mechanism of cancer occurrence and provide an efficient platform for drug screening. However, it is undeniable that the further application of humanized mice still faces multiple challenges. This review summarizes the construction approaches for humanized mice and their existing limitations. We also report the latest applications of humanized mice in preclinical evaluation for the treatment of cancer and point out directions for future optimization of these models.


Assuntos
Neoplasias , Camundongos , Humanos , Animais , Modelos Animais de Doenças , Neoplasias/terapia
5.
Int J Ophthalmol ; 16(12): 2011-2017, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38111928

RESUMO

AIM: To describe the outcome of using low-dose laser cycloplasty (LCP) in chronic angle-closure glaucoma (CACG). METHODS: A retrospective case series. Medical charts of CACG patients who underwent LCP in the Eye Hospital of Wenzhou Medical University were reviewed. The main outcomes included intraocular pressure (IOP), the number of glaucoma medication, anterior segment parameters and surgery-related complications. RESULTS: A total of 7 eyes of 7 CACG patients (age 38.9±11.0y) underwent LCP with a mean follow-up of 27.1±13.7mo (range 16-48mo). Following LCP, mean IOP and glaucoma medications decreased from 26.1±6.1 mm Hg with 3.1±1.1 glaucoma medications pre-treatment to 14.9±3.1 mm Hg (P=0.027) with 0.4±1.1 glaucoma medications (P=0.001) at final follow-up. The anterior chamber depth (ACD), angle opening distance500 and trabecular-iris angle increased from 1.65±0.33 mm, 0.05 mm (range 0-0.30 mm) and 5.1° (range, 0-31.97°) at baseline to 1.98±0.43 mm (P=0.073), 0.53 mm (range 0.42-0.91 mm, P=0.015), 45.9° (range, 40.2°-59.4°, (P=0.015) in the long-term follow-up, respectively. The deepening of ACD and reopening of anterior chamber angle (ACA) was observed in 6 eyes (85.7%). CONCLUSION: LCP is a promising treatment option for patients with CACG via reducing IOP and glaucoma medication without serious complications. In addition, LCP can bring a significant deepening in ACD and reopening of ACA.

6.
Hum Gene Ther ; 34(23-24): 1248-1256, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37917093

RESUMO

Distant metastasis and primary tumor relapse are the two main hurdles to the success of surgical treatment for cancer patients. Circulating tumor cells (CTCs) and incomplete surgical resection are the primary cause of distant metastasis and local recurrence of tumors, respectively. Chimeric antigen receptor (CAR)-modified T cells target residual carcinomas and CTCs hold the potential to inhibit primary recurrence and reduce tumor metastasis, but the experimental evidence is lacking. Here, we developed a surgery-induced tumor metastasis model in immunocompetent mice to investigate the efficacy of CAR-T cells therapy in preventing metastasis and local recurrence. We observed that subcutaneous tumor resection has induced a large number of CTCs intravasated into circulation. EpCAM-specific CAR-T was effective in clearing CTCs following surgical removal of the tumor. This resulted in less pulmonary metastasis and longer survival in mice when compared to mice treated with surgery followed by Mock-T cells infusion. In addition, the local relapse was obviously inhibited at the surgical site followed by EpCAM-CAR-T cell treatment. This study demonstrated that CAR-T cell therapy can be an adjuvant treatment following surgery to prevent tumor metastasis and inhibit primary tumor relapse for cancer patients.


Assuntos
Receptores de Antígenos Quiméricos , Humanos , Animais , Camundongos , Receptores de Antígenos Quiméricos/genética , Molécula de Adesão da Célula Epitelial/genética , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/patologia , Imunoterapia Adotiva/métodos , Recidiva , Terapia Baseada em Transplante de Células e Tecidos
7.
Nat Commun ; 14(1): 5654, 2023 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-37704629

RESUMO

Peptide-based therapeutics have gained attention as promising therapeutic modalities, however, their prevalent drawback is poor circulation half-life in vivo. In this paper, we report the selection of albumin-binding macrocyclic peptides from genetically encoded libraries of peptides modified by perfluoroaryl-cysteine SNAr chemistry, with decafluoro-diphenylsulfone (DFS). Testing of the binding of the selected peptides to albumin identified SICRFFC as the lead sequence. We replaced DFS with isosteric pentafluorophenyl sulfide (PFS) and the PFS-SICRFFCGG exhibited KD = 4-6 µM towards human serum albumin. When injected in mice, the concentration of the PFS-SICRFFCGG in plasma was indistinguishable from the reference peptide, SA-21. More importantly, a conjugate of PFS-SICRFFCGG and peptide apelin-17 analogue (N3-PEG6-NMe17A2) showed retention in circulation similar to SA-21; in contrast, apelin-17 analogue was cleared from the circulation after 2 min. The PFS-SICRFFC is the smallest known peptide macrocycle with a significant affinity for human albumin and substantial in vivo circulation half-life. It is a productive starting point for future development of compact macrocycles with extended half-life in vivo.


Assuntos
Albuminas , Albumina Sérica Humana , Humanos , Animais , Camundongos , Apelina , Albumina Sérica Humana/genética , Angiotensina II , Cisteína , Sulfetos
8.
ACS Omega ; 8(33): 30747-30756, 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37636964

RESUMO

Garbractin A (1), a structurally complicated polycyclic polyprenylated acylphloroglucinol (PPAP) with an unprecedented 4,11-dioxatricyclo[4.4.2.01,5] dodecane skeleton, was isolated from the fruits of Garcinia bracteata, along with five new biosynthetic analogues named garcibracteatones A-E (2-6). Their structures containing absolute configurations were revealed using spectroscopic data, the residual dipolar coupling-enhanced NMR approach, and quantum chemical calculations. The antihyperglycemic effect of these PPAPs (1-6) was evaluated using insulin-resistant HepG2 cells (IR-HepG2 cells) induced through palmitic acid (PA). Compounds 1, 3, and 4 were found to significantly promote glucose consumption in the IR-HepG2 cells and, therefore, may hold potential as candidates for treating hyperglycemia.

9.
Cancer Lett ; 568: 216287, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37392990

RESUMO

Chimeric antigen receptor-modified T (CAR-T) cell therapy has shown curable efficacy for treating hematological malignancies, while in solid tumors, the immunosuppressive microenvironment causes poor activation, expansion and survival of CAR-T cells, accounting mainly for the unsatisfactory efficacy. The artificial antigen-presenting cells (aAPCs) have been used for ex vivo expansion and manufacturing of CAR-T cells. Here, we constructed a K562 cell-based aAPCs expressing human epithelial cell adhesion molecule (EpCAM), chemokines (CCL19 and CCL21) and co-stimulatory molecular ligands (CD80 and 4-1BBL). Our data demonstrated that the novel aAPCs enhanced the expansion, and increased the immune memory phenotype and cytotoxicity of CAR-T cells recognizing EpCAM, in vitro. Of note, co-infusion CAR-T and aAPC enhances the infiltration of CAR-T cells in solid tumors, which has certain potential for the treatment of solid tumors Moreover, IL-2-9-21, a cytokine cocktail, prevents CAR-T cells from entering the state of exhaustion prematurely after continuous antigen engagement and boosts the anti-tumor activity of CAR-T cells co-infused with aAPCs. These data provide a new strategy to enhance the therapeutic potential of CAR-T cell therapy for the treatment of solid tumors.


Assuntos
Neoplasias , Receptores de Antígenos Quiméricos , Animais , Camundongos , Humanos , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/metabolismo , Molécula de Adesão da Célula Epitelial/metabolismo , Ligantes , Células Apresentadoras de Antígenos , Neoplasias/metabolismo , Imunoterapia Adotiva , Quimiocinas/metabolismo , Linfócitos T , Microambiente Tumoral
10.
Bioconjug Chem ; 34(8): 1477-1485, 2023 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-37523271

RESUMO

The design of imaging agents with high fluorine content is essential for overcoming the challenges associated with signal detection limits in 19F MRI-based molecular imaging. In addition to perfluorocarbon and fluorinated polymers, fluorinated peptides offer an additional strategy for creating sequence-defined 19F magnetic resonance imaging (MRI) imaging agents with a high fluorine signal. Our previously reported unstructured trifluoroacetyllysine-based peptides possessed good physiochemical properties and could be imaged at high magnetic field strength. However, the low detection limit motivated further improvements in the fluorine content of the peptides as well as removal of nonspecific cellular interactions. This research characterizes several new highly fluorinated synthetic peptides composed of highly fluorinated amino acids. 19F NMR analysis of peptides TB-1 and TB-9 led to highly overlapping, intense fluorine resonances and acceptable aqueous solubility. Flow cytometry analysis and fluorescence microscopy further showed nonspecific binding could be removed in the case of TB-9. As a preliminary experiment toward developing molecular imaging agents, a fluorinated EGFR-targeting peptide (KKKFFKK-ßA-YHWYGYTPENVI) and an EGFR-targeting protein complex E1-DD bioconjugated to TB-9 were prepared. Both bioconjugates maintained good 19F NMR performance in aqueous solution. While the E1-DD-based imaging agent will require further engineering, the success of cell-based 19F NMR of the EGFR-targeting peptide in A431 cells supports the potential use of fluorinated peptides for molecular imaging.


Assuntos
Flúor , Imageamento por Ressonância Magnética , Flúor/química , Espectroscopia de Ressonância Magnética , Peptídeos , Receptores ErbB
11.
Eye Vis (Lond) ; 10(1): 28, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37391810

RESUMO

BACKGROUND: To report the incidence and clinical characteristics of aqueous misdirection (AM) after glaucoma surgery in Chinese patients with primary angle-closure glaucoma. METHODS: Medical records of all patients diagnosed with primary angle-closure glaucoma who underwent glaucoma surgery in the Eye Hospital of Wenzhou Medical University between January 2012 and December 2021 were retrospectively reviewed. Cases of AM were identified through a keyword-based search. The incidence of AM was calculated. Demographic and clinical characteristics of the AM patients were also described. RESULTS: A total of 5044 eyes with primary angle-closure glaucoma were included (mean age 65.81 ± 9.96 years, 68.11% women). Thirty-eight eyes developed AM, presenting an overall incidence of 0.75%. The mean time interval between surgery and first record of AM diagnosis was 2.57 ± 5.24 months (range, 0 day to 24 months). The incidence of AM was significantly higher in patients aged ≤ 40 years (21.28%) and those aged 40-50 years (3.32%), compared to those > 50 years (0.42%) (P < 0.001). AM developed much more frequently among patients with chronic angle-closure glaucoma (1.30%), compared to those with acute angle-closure glaucoma (0.32%, P < 0.001). Eleven eyes (0.37%) developed AM following non-filtering surgery compared to 24 eyes (2.27%) after filtering surgery (P < 0.001). CONCLUSION: The incidence of AM after glaucoma surgery was 0.75% in Chinese patients with primary angle closure glaucoma. Younger age, chronic angle-closure glaucoma, and undergoing filtering surgery, were identified as associated risk factors for developing AM. Phacoemulsification may have less risk of developing AM compared to filtering surgery.

12.
Biomed Opt Express ; 14(5): 2225-2239, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37206151

RESUMO

Fluorescence molecular tomography can combine two-dimensional fluorescence imaging with anatomical information to reconstruct three-dimensional images of tumors. Reconstruction based on traditional regularization with tumor sparsity priors does not take into account that tumor cells form clusters, so it performs poorly when multiple light sources are used. Here we describe reconstruction based on an "adaptive group least angle regression elastic net" (AGLEN) method, in which local spatial structure correlation and group sparsity are integrated with elastic net regularization, followed by least angle regression. The AGLEN method works iteratively using the residual vector and a median smoothing strategy in order to adaptively obtain a robust local optimum. The method was verified using numerical simulations as well as imaging of mice bearing liver or melanoma tumors. AGLEN reconstruction performed better than state-of-the-art methods with different sizes of light sources at different distances from the sample and in the presence of Gaussian noise at 5-25%. In addition, AGLEN-based reconstruction accurately imaged tumor expression of cell death ligand-1, which can guide immunotherapy.

13.
Chronobiol Int ; 40(3): 353-360, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36912010

RESUMO

The objective of this scoping review was to synthesize the available evidence and evaluate the effectiveness of chronoradiotherapy interventions in cervical cancer patients. This scoping review was performed by searching in the PubMed, Cochrane Library, Embase, Web of Science, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), China National Knowledge Infrastructure (CNKI), Wanfang, Wenpu, and Chinese Biomedical Literature (CBM) databases. Databases were searched for studies published in English or Chinese from inception to 21 May 2021, and reference lists of relevant reports were scanned. Two investigators independently screened eligible studies in accordance with predetermined eligibility criteria and extracted data. The included studies were summarized and analyzed. Five studies including a total of 422 patients with cervical cancer were included in the scoping review; four studies were Chinese, and one was Indian. Main themes identified included the efficiency of chronoradiotherapy and relevant toxic and side effects, including diarrhea toxicity, hematologic toxicity, myelosuppression, gastrointestinal mucositis, and skin reactions. Administration of radiotherapy at different times of the day resulted in similar efficacy. However, the toxic side effects of morning radiotherapy (MR) and evening radiotherapy (ER) differed, with radiotherapy in the evening leading to more severe hematologic toxicity and myelosuppression. There were conflicting conclusions about gastrointestinal reactions with chronoradiotherapy, and further studies are needed. Radiation responses may be associated with circadian genes, through the influence of cell cycles and apoptosis.


Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/radioterapia , Ritmo Circadiano , China
14.
J Nanobiotechnology ; 21(1): 112, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-36978072

RESUMO

Residual lesions in the tumor bed have been a challenge for conventional white-light breast-conserving surgery. Meanwhile, lung micro-metastasis also requires improved detection methods. Intraoperative accurate identification and elimination of microscopic cancer can improve surgery prognosis. In this study, a smart fibronectin-targeting and metalloproteinase-activatable imaging probe CREKA-GK8-QC is developed. CREKA-GK8-QC possesses an average diameter of 21.7 ± 2.5 nm, excellent MMP-9 protein responsiveness and no obvious cytotoxicity. In vivo experiments demonstrate that NIR-I fluorescence imaging of CREKA-GK8-QC precisely detects orthotopic breast cancer and micro-metastatic lesions (nearly 1 mm) of lungs with excellent imaging contrast ratio and spatial resolution. More notably, fluorescence image-guided surgery facilitates complete resection and avoids residual lesions in the tumor bed, improving survival outcomes. We envision that our newly developed imaging probe shows superior capacity for specific and sensitive targeted imaging, as well as providing guidance for accurate surgical resection of breast cancer.


Assuntos
Neoplasias da Mama , Cirurgia Assistida por Computador , Feminino , Humanos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Fibronectinas , Corantes Fluorescentes/metabolismo , Metaloproteases , Imagem Óptica/métodos , Cirurgia Assistida por Computador/métodos
15.
Eur J Oncol Nurs ; 63: 102258, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36821887

RESUMO

OBJECTIVE: Breast cancer-related lymphedema (BCRL) is a common post-operative complication in patients with breast cancer. Here, we sought to develop and validate a predictive model of BCRL in Chinese patients with breast cancer. METHODS: Clinical and demographic data on patients with breast cancer were collected between 2016 and 2021 at a Cancer Hospital in China. A nomogram for predicting the risk of lymphedema in postoperative patients with breast cancer was constructed and verified using R 3.5.2 software. Model performance was evaluated using area under the ROC curve (AUC) and goodness-of-fit statistics, and the model was internally validated. RESULTS: A total of 1732 postoperative patients with breast cancer, comprising 1212 and 520 patients in the development and validation groups, respectively, were included. Of these 438 (25.39%) developed lymphedema. Significant predictors identified in the predictive model were time since breast cancer surgery, level of lymph node dissection, number of lymph nodes dissected, radiotherapy, and postoperative body mass index. At the 31.9% optimal cut-off the model had AUC values of 0.728 and 0.710 in the development and validation groups, respectively. Calibration plots showed a good match between predicted and observed rates. In decision curve analysis, the net benefit of the model was better between threshold probabilities of 10%-80%. CONCLUSION: The model has good discrimination and accuracy for lymphedema risk assessment, which can provide a reference for individualized clinical prediction of the risk of BCRL. Multicenter prospective trials are required to verify the predictive value of the model.


Assuntos
Linfedema Relacionado a Câncer de Mama , Neoplasias da Mama , Linfedema , Humanos , Feminino , Neoplasias da Mama/radioterapia , Estudos Prospectivos , Fatores de Risco , Linfedema/etiologia , Estudos Retrospectivos
16.
Nat Commun ; 14(1): 238, 2023 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-36646707

RESUMO

Emerging evidence shows that the biomechanical environment is required to support cancer stem cells (CSCs), which play a crucial role in drug resistance. However, how mechanotransduction signals regulate CSCs and its clinical significance has remained unclear. Using clinical-practice ultrasound elastography for patients' lesions and atomic force microscopy for surgical samples, we reveal that increased matrix stiffness is associated with poor responses to neoadjuvant chemotherapy, worse prognosis, and CSC enrichment in patients with breast cancer. Mechanically, TAZ activated by biomechanics enhances CSC properties via phase separation with NANOG. TAZ-NANOG phase separation, which is dependent on acidic residues in the N-terminal activation domain of NANOG, promotes the transcription of SOX2 and OCT4. Therapeutically, targeting NANOG or TAZ reduces CSCs and enhances the chemosensitivity in vivo. Collectively, this study demonstrated that the phase separation of a pluripotency transcription factor links mechanical cues in the niche to the fate of CSCs.


Assuntos
Neoplasias da Mama , Mecanotransdução Celular , Proteína Homeobox Nanog , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional , Feminino , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proteína Homeobox Nanog/genética , Células-Tronco Neoplásicas/patologia , Fatores de Transcrição/genética , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional/genética , Nicho de Células-Tronco
17.
IEEE Trans Biomed Eng ; 70(1): 296-306, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35820000

RESUMO

Fluorescence Molecular Tomography (FMT), providing thethree-dimensional fluorescent distribution information of specific molecular probes in tumors, is widely applied to detect in vivo tumors. However, the ill-posedness of reconstruction greatly affects the resolution of FMT. Traditional methods have introduced different regularization terms to solve this problem, but there are still challenges for the high-resolution reconstruction of small tumors under complex conditions. In this paper, we proposed an elastic net method optimized by the relaxed Alternating Direction Method of Multipliers (EN-RADMM) to improve the reconstruction resolution for small tumors. The objective function consisted of the Least-Square term and elastic net regularization. Relaxation, equivalent deformation directing at ill-posed equations, and LU decomposition were applied to accelerate algorithm convergence and improve solution accuracy. Thereby, the light from small tumors can be precisely reconstructed. We designed a series of digital tumor models with different distances, sizes, and shapes to verify the performance of EN-RADMM, and utilized the real glioma-bearing mouse models to further verify its feasibility and accuracy. The simulation results demonstrated that EN-RADMM can achieve significantly higher resolution and reconstruction accuracy of morphology and position with less time compared with other advanced methods. Furthermore, in vivo experiments proved the broad prospect of EN-RADMM in pre-clinical application of FMT reconstruction.


Assuntos
Processamento de Imagem Assistida por Computador , Neoplasias , Animais , Camundongos , Processamento de Imagem Assistida por Computador/métodos , Imagens de Fantasmas , Tomografia/métodos , Algoritmos
18.
Cell Mol Neurobiol ; 43(2): 683-696, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35556192

RESUMO

At present, the diagnosis of ischemic stroke mainly depends on neuroimaging technology, but it still has many limitations. Therefore, it is very important to find new biomarkers of ischemic stroke. Recently, ß-actin has attracted extensive attention as a biomarker of a variety of cancers. Although several recent studies have been investigating its role in ischemic stroke and other cerebrovascular diseases, the understanding of this emerging biomarker in neurology is still limited. We examined human and preclinical studies to gain a comprehensive understanding of the literature on the subject. Most relevant literatures focus on preclinical research, and pay more attention to the role of ß-actin in the process of cerebral ischemia, but some recent literatures reported that in human studies, serum ß-actin increased significantly in the early stage of acute cerebral ischemia. This review will investigate the basic biology of ß-actin, pay attention to the potential role of serum ß-actin as an early diagnostic blood biomarker of ischemic stroke, and explore its potential mechanism in ischemic stroke and new strategies for stroke treatment in the future.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Actinas , Biomarcadores
19.
Front Oncol ; 12: 1021453, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36457490

RESUMO

Objectives: To investigate the short-term efficacy and radiotoxicity 3.543of chronoradiotherapy in patients with cervical cancer. We also examined the overall symptom score and quality of life (QOL) of patients who underwent morning radiotherapy and evening radiotherapy. Methods: We conducted a multicenter randomized controlled trial to compare the effects of morning radiotherapy (9:00-11:00 AM) with evening radiotherapy (7:00-9:00 PM) in cervical cancer patients receiving radiotherapy. From November 2021 to June 2022, 114 cervical cancer patients admitted to eight cancer center hospitals in Tianjin, Chongqing, Hubei, Shanxi, Shandong, Shaanxi, Hebei, and Cangzhou were randomly divided into the morning radiotherapy group (MG; N = 61) and the evening radiotherapy group (EG; N = 53). The short-term efficacy of radiotherapy on cervical cancer patients at different time points and the occurrence of radiotoxicity were explored after patients had undergone radiotherapy. Results: The total effective response (partial remission [PR] + complete remission [CR]) rate was similar across the two groups (93.5% vs. 96.3%, p > 0.05). However, the incidence of bone marrow suppression and intestinal reaction in the two groups were significantly different (p < 0.05). The patients in the MG had significantly higher Anderson symptom scores than patients in the EG (21.64 ± 7.916 vs. 18.53 ± 4.098, p < 0.05). In terms of physical activity, functional status, and overall QOL, the MG had significantly lower scores than the EG (p < 0.05). No other measures showed a significant difference between the groups. Conclusion: The radiotherapy effect of the MG was consistent with that of the EG. The incidence of radiation enteritis and radiation diarrhea in the MG was significantly higher than that in the EG; however, bone marrow suppression and blood toxicity in the EG were more serious than in the MG. Because of the small sample size of the study, we only examined the short-term efficacy of radiotherapy. Therefore, further clinical trials are needed to verify the efficacy and side effects of chronoradiotherapy. Clinical Trial Registration: http://www.chictr.org.cn/searchproj.aspx, Registration Number: ChiCTR2100047140.

20.
J Vasc Access ; : 11297298221095039, 2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36527184

RESUMO

BACKGROUND: Peripherally inserted central catheters (PICCs) are performed for medium and long term intravenous therapy. The most recent guidelines recommend the use of ultrasound-guided venipuncture to reduce surgery-related complications. In recent years, bedside ultrasound has also been used as evidence of accuracy in tip navigation and tip positioning. This paper is aimed to investigate using tip navigation with the ultrasonic technique and intracavitary electrocardiogram during the catheterization, and to suggest a feasible and safe standardized protocol for clinical practice. METHODS: A total of 1727 tumor clients who suffered from combined the ultrasonic technique with intracavitary electrocardiogram (ECG + US group) to confirm the tip location of PICC were included in Peking Union Medical College Hospital in 2020. And based on electronic medical records according to the types of cancer as 1:1 to select 1727 cases who only underwent electrocardiogram (ECG group) to verify the tip location of catheters with the same team in 2019. Compared two groups of purpose of catheter, insertion site of upper limbs, times of puncture and delivery catheters, tip location and malposition of peripherally inserted central catheter, and analysis of the safety and feasibility. RESULTS: There were no significant differences between the two groups in the purpose of catheter, insertion site of upper limbs, times of puncture, and delivery catheters. The percentage of optimal tip location in ECG + US group was significantly higher than that in ECG group, and the rate of malposition of catheters was obviously lower than that in ECG group (p < 0.001). CONCLUSIONS: Tip navigation based with ultrasound and intracavitary electrocardiogram has high accuracy to confirm tip location of PICC, and it is also feasible and safe, which can not only to make up for the deficiency of patients without surface P waves who could not be applied ECG but also to fit for all patients.

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