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2.
J Am Med Inform Assoc ; 31(5): 1199-1205, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38563821

RESUMO

OBJECTIVE: This article presents the National Healthcare Safety Network (NHSN)'s approach to automation for public health surveillance using digital quality measures (dQMs) via an open-source tool (NHSNLink) and piloting of this approach using real-world data in a newly established collaborative program (NHSNCoLab). The approach leverages Health Level Seven Fast Healthcare Interoperability Resources (FHIR) application programming interfaces to improve data collection and reporting for public health and patient safety beginning with common, clinically significant, and preventable patient harms, such as medication-related hypoglycemia, healthcare facility-onset Clostridioides difficile infection, and healthcare-associated venous thromboembolism. CONCLUSIONS: The NHSN's FHIR dQMs hold the promise of minimizing the burden of reporting, improving accuracy, quality, and validity of data collected by NHSN, and increasing speed and efficiency of public health surveillance.


Assuntos
Infecções por Clostridium , Segurança do Paciente , Humanos , Estados Unidos , Qualidade da Assistência à Saúde , Coleta de Dados , Centers for Disease Control and Prevention, U.S.
3.
Proc Natl Acad Sci U S A ; 121(15): e2321759121, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38579009

RESUMO

Adjacent plant cells are connected by specialized cell wall regions, called middle lamellae, which influence critical agricultural characteristics, including fruit ripening and organ abscission. Middle lamellae are enriched in pectin polysaccharides, specifically homogalacturonan (HG). Here, we identify a plant-specific Arabidopsis DUF1068 protein, called NKS1/ELMO4, that is required for middle lamellae integrity and cell adhesion. NKS1 localizes to the Golgi apparatus and loss of NKS1 results in changes to Golgi structure and function. The nks1 mutants also display HG deficient phenotypes, including reduced seedling growth, changes to cell wall composition, and tissue integrity defects. These phenotypes are comparable to qua1 and qua2 mutants, which are defective in HG biosynthesis. Notably, genetic interactions indicate that NKS1 and the QUAs work in a common pathway. Protein interaction analyses and modeling corroborate that they work together in a stable protein complex with other pectin-related proteins. We propose that NKS1 is an integral part of a large pectin synthesis protein complex and that proper function of this complex is important to support Golgi structure and function.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Adesão Celular/genética , Pectinas/metabolismo , Complexo de Golgi/genética , Complexo de Golgi/metabolismo , Parede Celular/metabolismo
5.
J Hazard Mater ; 470: 134235, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38608585

RESUMO

The misuse of aromatic amines like 4-chloroaniline (4-CA) has led to severe environmental and health issues. However, it's difficult to be utilized by microorganisms for degradation. Nano-zero-valent iron (nZVI) is a promising material for the remediation of chloroaniline pollution, however, the synergistic effect and mechanism of nZVI with microorganisms for the degradation of 4-CA are still unclear. This study investigated the potential of 4-CA removal by the synergistic system involving nZVI and 4-CA degrading microbial flora. The results indicate that the addition of nZVI significantly enhanced the bio-degradation rate of 4-CA from 43.13 % to 62.26 %. Under conditions involving 0.1 % nZVI addition at a 24-hour interval, pH maintained at 7, and glucose as an external carbon source, the microbial biomass, antioxidant enzymes, and dehydrogenase were significantly increased, and the optimal 4-CA degradation rate achieved 68.79 %. Additionally, gas chromatography-mass spectrometry (GC-MS) analysis of intermediates indicated that the addition of nZVI reduced compounds containing benzene rings and enhanced the dechlorination efficiency. The microbial community remained stable during the 4-CA degradation process. This study illustrates the potential of nZVI in co-microbial remediation of 4-CA compounds in the environment.


Assuntos
Compostos de Anilina , Biodegradação Ambiental , Ferro , Poluentes Químicos da Água , Compostos de Anilina/química , Compostos de Anilina/metabolismo , Ferro/química , Ferro/metabolismo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/química , Purificação da Água/métodos , Bactérias/metabolismo , Nanopartículas Metálicas/química
6.
J Thorac Dis ; 16(2): 1730-1737, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38505078

RESUMO

Background: Patients with tricuspid bioprosthetic structural valve degeneration (SVD) often present with right ventricular enlargement and severe dysfunction, which cause a higher risk for redo cardiac surgery. In 2019, our center innovated using the J-valve system for valve-in-valve (ViV) implantation to treat tricuspid bioprosthetic SVD. The purpose of this study was to summarize the clinical effect after 1-year follow-up. Case Description: From April 2019 to October 2019, two cases of tricuspid bioprosthetic dysfunction were treated with the J-valve system. Both patients were male, aged 46 and 67 years, respectively. The preoperative evaluation showed that the risk of conventional redo open heart surgery was high. The J-valve implantation was successful in both cases. One patient had slight valve displacement when the transporter was withdrawn during the operation, and a second J-valve was implanted in an ideal position. There was no death, no delayed valve displacement, and no readmission during the follow-up period of 12 months. In both cases, there was an absence of trace tricuspid regurgitation. After 6 months of anticoagulation with warfarin, the patients were converted to long-term aspirin treatment. Conclusions: The ViV technique with J-valve is feasible and effective in treating tricuspid bioprosthetic SVD in high-risk patients, avoiding cardiopulmonary bypass and conventional thoracotomy injury.

7.
Front Cardiovasc Med ; 11: 1360763, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38433755

RESUMO

Background: The clinical prognosis of mitral valve surgery at morning, afternoon, and evening is not yet clear. The aim of the study is to investigate the impact of different time periods of surgery in the morning, afternoon and evening on the short-term and long-term results of mitral valve surgery. Methods: From January 2018 to December 2020, 947 patients with mitral valve surgery in our department were selected. These patients were divided into 3 groups according to the starting time of surgery. Morning group (operation start time 8:00-10:30, n = 231), afternoon group (operation start time 12:00-14:30, n = 543), and evening group (operation start time 17:30-20:00, n = 173). The short-term and long-term results of the three groups were compared. Results: There were no significant difference in the long-term mortality, long-term risk of stroke and reoperation. And there were no significant difference in in-hospital outcomes, including mortality, stroke, cardiopulmonary bypass time, aortic cross clamp time, mitral valve repair convert to mitral valve replacement, number of aortic cross clamp ≥2 times, unplanned secondary surgery during hospitalization (including thoracotomy hemostasis, thoracotomy exploration, redo mitral valve surgery, and debridement), intra-aortic balloon pump, extracorporeal membrane oxygenation, continuous renal replacement therapy, mechanical ventilation time, and intensive care unit length of stay. Conclusion: There is no significant difference in the risk of short-term and long-term survival and adverse events after mitral valve surgery at different time periods in the morning, afternoon, and evening. Mitral valve surgery at night is safe.

8.
J Thorac Dis ; 16(1): 593-603, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38410558

RESUMO

Background: Due to the influence of anatomical structure, replacing the bicuspid valve using transcatheter aortic valve replacement (TAVR) would increase the risk of perivalvular leakage and conduction block, affecting the hemodynamic effect of the interventional valve. In this study, for bicuspid and tricuspid valves, we implemented different valve selection strategies to explore the safety and effectiveness of TAVR in the treatment of bicuspid aortic stenosis with "down-size" interventional valves using the VenusA-valve system. Methods: The operation was performed with the VenusA-valve via transfemoral approach. The selected valves were appropriately sized based on the results of transthoracic echocardiography (TTE), contrast-enhanced computed tomography (CT), and the morphology of intraoperative pre-dilation balloons. For tricuspid valve cases, the VenusA valve is usually larger than the annulus diameter, whereas the "down-size" approach was adopted for bicuspid aortic valve (BAV) cases. The shape of the pre-dilation balloon allowed further sizing of the annulus diameter by the degree of lumbar constriction of the balloon, aiding in intervention valve size selection, particularly in cases of BAVs. Results: A total of 65 patients underwent TAVR for aortic stenosis with VenusA-valve systems. Of these, 29 cases had a BAV and 36 cases had a tricuspid aortic valve (TAV). The distribution of VenusA-valve sizes differed between TAV and BAV cases (P=0.007). Furthermore, there was a significant decrease in the average mean gradient in TAV patients from 54.7 to 12.2 mmHg (P<0.001), and in BAV patients from 61.6 to 14.3 mmHg (P<0.001). The percentage of paravalvular leakage greater than mild was 6.90% in the BAVs and 5.56% in the TAVs at procedural outcomes (P=0.955). The mean follow-up period was 22.23 months (range, 12 to 39 months). The proportion of New York Heart Association (NYHA) class III/IV decreased from 78.5% preoperatively to 11.3% at the last follow-up (P<0.001). A total of 27 patients with TAV and 19 patients with BAV underwent TTE at 1-year follow-up after operation. There was no significant contrast in the average pressure difference between TAVs and BAVs at 1-year follow-up (11.9 vs. 14.3 mmHg, P=0.18). Conclusions: The VenusA-valve for TAVR produced positive clinical outcomes and valve functionality in both BAVs and TAVs. In the case of BAVs, selecting a smaller interventional valve size was deemed viable.

9.
Chin Neurosurg J ; 10(1): 5, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38326922

RESUMO

BACKGROUND: Moyamoya disease (MMD) is a rare and complex cerebrovascular disorder characterized by the progressive narrowing of the internal carotid arteries and the formation of compensatory collateral vessels. The etiology of MMD remains enigmatic, making diagnosis and management challenging. The MOYAOMICS project was initiated to investigate the molecular underpinnings of MMD and explore potential diagnostic and therapeutic strategies. METHODS: The MOYAOMICS project employs a multidisciplinary approach, integrating various omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, to comprehensively examine the molecular signatures associated with MMD pathogenesis. Additionally, we will investigate the potential influence of gut microbiota and brain-gut peptides on MMD development, assessing their suitability as targets for therapeutic strategies and dietary interventions. Radiomics, a specialized field in medical imaging, is utilized to analyze neuroimaging data for early detection and characterization of MMD-related brain changes. Deep learning algorithms are employed to differentiate MMD from other conditions, automating the diagnostic process. We also employ single-cellomics and mass cytometry to precisely study cellular heterogeneity in peripheral blood samples from MMD patients. CONCLUSIONS: The MOYAOMICS project represents a significant step toward comprehending MMD's molecular underpinnings. This multidisciplinary approach has the potential to revolutionize early diagnosis, patient stratification, and the development of targeted therapies for MMD. The identification of blood-based biomarkers and the integration of multiple omics data are critical for improving the clinical management of MMD and enhancing patient outcomes for this complex disease.

10.
J Stroke Cerebrovasc Dis ; 33(3): 107575, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38232582

RESUMO

AIM: This study aimed to evaluate the feasibility of transcranial color-coded sonography (TCCS) and contrast-enhanced ultrasound (CEUS) in assessing middle cerebral artery (MCA) stem stenosis or occlusion compared to digital subtraction angiography (DSA). METHODS: A total of 48 cases including 96 MCAs suspected stem stenosis or obstruction in the MCA were assessed by TCCS, CE-TCCS, and DSA. The diameters of the most severe stenosis (Ds), proximal normal artery (Dn), and diameter stenosis rate of MCA were measured using both the color doppler flow imaging (CDFI) modality of TCCS or CEUS and the CEUS imaging modality. The intraclass correlation coefficients (ICCs) and 95 % confidence intervals (CI) were evaluated, and a weighted Kappa value was used to evaluate the intra-observer agreement, inter-observer agreement, agreement between CDFI modality and DSA stenosis or occlusion, and agreement between CEUS imaging modality and DSA stenosis or occlusion. RESULTS: The ICC results indicated excellent repeatability and reproducibility (all ICCs > 0.75; weighted Kappa values >0.81). Compared with DSA, the weighted Kappa values and 95 % CIs of stenosis (the first measurement was taken by two observers) of CDFI modality and CEUS imaging modality were 0.175 (0.041, 0.308) and 0.779 (0.570, 0.988) for observers A and 0.181 (0.046, 0.316) and 0.779 (0.570, 0.988) for observers B respectively. CONCLUSION: This study indicates that inter- and intra-observer agreements were good for the direct method of measuring percentages of MCA stenosis by TCCS and CEUS. CEUS imaging modality is a new and reliable imaging modality approach to evaluate the MCAs stenosis and occlusion.


Assuntos
Transtornos Cerebrovasculares , Artéria Cerebral Média , Humanos , Artéria Cerebral Média/diagnóstico por imagem , Constrição Patológica , Angiografia Digital/métodos , Reprodutibilidade dos Testes , Estudos de Viabilidade , Ultrassonografia Doppler Transcraniana/métodos , Sensibilidade e Especificidade
11.
Int J Nanomedicine ; 19: 389-401, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38250194

RESUMO

Introduction: Ultrasensitive bacterial detection methods are crucial to ensuring accurate diagnosis and effective clinical monitoring, given the significant threat bacterial infections pose to human health. The aim of this study is to develop a biosensor with capabilities for broad-spectrum bacterial detection, rapid processing, and cost-effectiveness. Methods: A magnetically-assisted SERS biosensor was designed, employing wheat germ agglutinin (WGA) for broad-spectrum recognition and antibodies for specific capture. Gold nanostars (AuNSs) were sequentially modified with the Raman reporter molecules and WGA, creating a versatile SERS tag with high affinity for a diverse range of bacteria. Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) antibody-modified Fe3O4 magnetic gold nanoparticles (MGNPs) served as the capture probes. Target bacteria were captured by MGNPs and combined with SERS tags, forming a "sandwich" composite structure for bacterial detection. Results: AuNSs, with a core size of 65 nm, exhibited excellent storage stability (RSD=5.6%) and demonstrated superior SERS enhancement compared to colloidal gold nanoparticles. Efficient binding of S. aureus and P. aeruginosa to MGNPs resulted in capture efficiencies of 89.13% and 85.31%, respectively. Under optimized conditions, the developed assay achieved a limit of detection (LOD) of 7 CFU/mL for S. aureus and 5 CFU/mL for P. aeruginosa. The bacterial concentration (10-106 CFU/mL) showed a strong linear correlation with the SERS intensity at 1331 cm-1. Additionally, high recoveries (84.8% - 118.0%) and low RSD (6.21% - 11.42%) were observed in spiked human urine samples. Conclusion: This study introduces a simple and innovative magnetically-assisted SERS biosensor for the sensitive and quantitative detection of S. aureus or P. aeruginosa, utilizing WGA and antibodies. The developed biosensor enhances the capabilities of the "sandwich" type SERS biosensor, offering a novel and effective platform for accurate and timely clinical diagnosis of bacterial infections.


Assuntos
Nanopartículas Metálicas , Infecções Estafilocócicas , Humanos , Ouro , Staphylococcus aureus , Bactérias , Anticorpos
12.
Quant Imaging Med Surg ; 14(1): 1141-1154, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38223070

RESUMO

Background: Although imaging techniques provide information about the morphology and stability of carotid plaque, they are operator dependent and may miss certain subtleties. A variety of radiomics models for carotid plaque have recently been proposed for identifying vulnerable plaques and predicting cardiovascular and cerebrovascular diseases. The purpose of this review was to assess the risk of bias, reporting, and methodological quality of radiomics models for carotid atherosclerosis plaques. Methods: A systematic search was carried out to identify available literature published in PubMed, Web of Science, and the Cochrane Library up to March 2023. Studies that developed and/or validated machine learning models based on radiomics data to identify and/or predict unfavorable cerebral and cardiovascular events in carotid plaque were included. The basic information of each piece of included literature was identified, and the reporting quality, risk of bias, and radiomics methodology quality were assessed according the TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) checklist, the Prediction Model Risk of Bias Assessment Tool (PROBAST), and the radiomics quality score (RQS), respectively. Results: A total of 2,738 patients from 19 studies were included. The mean overall TRIPOD adherence rate was 66.1% (standard deviation 12.8%), with a range of 45-87%. All studies had a high overall risk of bias, with the analysis domain being the most common source of bias. The mean RQS was 9.89 (standard deviation 5.70), accounting for 27.4% of the possible maximum value of 36. The mean area under the curve for diagnostic or predictive properties of these included radiomics models was 0.876±0.09, with a range of 0.741-0.989. Conclusions: Radiomics models may have value in the assessment of carotid plaque, the overall scientific validity and reporting quality of current carotid plaque radiomics reports are still lacking, and many barriers must be overcome before these models can be applied in clinical practice.

13.
Small ; : e2310014, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38193262

RESUMO

Here, a multiplex surface-enhanced Raman scattering (SERS)-immunochromatography (ICA) platform is presented using a graphene oxide (GO)-based film-like magnetic tag (GFe-DAu-D/M) that effectively captures and detects multiple bacteria in complex specimens. The 2D GFe-DAu-D/M tag with universal bacterial capture ability is fabricated through the layer-by-layer assembly of one layer of small Fe3 O4 nanoparticles (NPs) and two layers of 30 nm AuNPs with a 0.5 nm built-in nanogap on monolayer GO nanosheets followed by co-modification with 4-mercaptophenylboronic acid (MPBA) and 5,5'-dithiobis-(2-nitrobenzoic acid).The GFe-DAu-D/M enabled the rapid enrichment of multiple bacteria by MPBA and quantitative analysis of target bacteria on test lines by specific antibodies, thus achieving multiple signal amplification of magnetic enrichment effect and multilayer dense hotspots and eliminating matrix interference in real-world applications. The developed technology can directly and simultaneously diagnose three major pathogens (Staphylococcus aureus, Pseudomonas aeruginosa, and Salmonella typhimurium) with detection limits down to the level of 10 cells mL-1 . The good performance of the proposed method in the detection of real urinary tract infection specimens is also demonstrated, suggesting the great potential of the GFe-DAu-D/M-ICA platform for the highly sensitive monitoring of bacterial infections or contamination.

14.
ACS Cent Sci ; 10(1): 19-27, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38292604

RESUMO

Lysosomes have long been known for their acidic lumens and efficient degradation of cellular byproducts. In recent years, it has become clear that their function is far more sophisticated, involving multiple cell signaling pathways and interactions with other organelles. Unfortunately, their acidic interior, fast dynamics, and small size make lysosomes difficult to image with fluorescence microscopy. Here we report a far-red small molecule, HMSiR680-Me, that fluoresces only under acidic conditions, causing selective labeling of acidic organelles in live cells. HMSiR680-Me can be used alongside other far-red dyes in multicolor imaging experiments and is superior to existing lysosome probes in terms of photostability and maintaining cell health and lysosome motility. We demonstrate that HMSiR680-Me is compatible with overnight time-lapse experiments as well as time-lapse super-resolution microscopy with a frame rate of 1.5 fps for at least 1000 frames. HMSiR680-Me can also be used alongside silicon rhodamine dyes in a multiplexed super-resolution microscopy experiment to visualize interactions between mitochondria and lysosomes with only a single excitation laser and simultaneous depletion. We envision this dye permitting a more detailed study of the role of lysosomes in dynamic cellular processes and disease.

15.
Am J Physiol Cell Physiol ; 326(2): C647-C658, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38189133

RESUMO

Thoracic aortic aneurysm/dissection (TAAD) is a lethal vascular disease, and several pathological factors participate in aortic medial degeneration. We previously discovered that the complement C3a-C3aR axis in smooth muscle cells promotes the development of thoracic aortic dissection (TAD) through regulation of matrix metalloproteinase 2. However, discerning the specific complement pathway that is activated and elucidating how inflammation of the aortic wall is initiated remain unknown. We ascertained that the plasma levels of C3a and C5a were significantly elevated in patients with TAD and that the levels of C3a, C4a, and C5a were higher in acute TAD than in chronic TAD. We also confirmed the activation of the complement in a TAD mouse model. Subsequently, knocking out Cfb (Cfb) or C4 in mice with TAD revealed that the alternative pathway and Cfb played a significant role in the TAD process. Activation of the alternative pathway led to generation of the anaphylatoxins C3a and C5a, and knocking out their receptors reduced the recruitment of inflammatory cells to the aortic wall. Moreover, we used serum from wild-type mice or recombinant mice Cfb as an exogenous source of Cfb to treat Cfb KO mice and observed that it exacerbated the onset and rupture of TAD. Finally, we knocked out Cfb in the FBN1C1041G/+ Marfan-syndrome mice and showed that the occurrence of TAA was reduced. In summary, the alternative complement pathway promoted the development of TAAD by recruiting infiltrating inflammatory cells. Targeting the alternative pathway may thus constitute a strategy for preventing the development of TAAD.NEW & NOTEWORTHY The alternative complement pathway promoted the development of TAAD by recruiting infiltrating inflammatory cells. Targeting the alternative pathway may thus constitute a strategy for preventing the development of TAAD.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Azidas , Desoxiglucose/análogos & derivados , Humanos , Camundongos , Animais , Via Alternativa do Complemento , Metaloproteinase 2 da Matriz , Aneurisma da Aorta Torácica/genética , Aneurisma da Aorta Torácica/metabolismo , Aneurisma da Aorta Torácica/patologia , Dissecção Aórtica/genética , Inflamação
16.
Medicine (Baltimore) ; 103(4): e36948, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38277531

RESUMO

BACKGROUND: With the advancement of diagnostic technology, true acute undifferentiated leukemia (AUL) is becoming more rare, and AUL with extramedullary sarcoma has not been reported. CASE PRESENTATION: This article reports a case of AUL with extramedullary sarcoma. Flow cytometric analysis of the bone marrow and lymph nodes indicated that the tumor cells of both were of the same origin and mainly expressed stem cell markers and CD7, no myeloid-specific markers, T-lymphoblastic-related markers, and B-lymphoblastic-related markers. Although the priming regimen combined with azacitidine was ineffective, complete remission was achieved by switching to azacitidine combined with HIA (homoharringtonine, idarubicin plus Ara-C). CONCLUSION: To diagnosis de novo acute leukemia with extensive and comprehensive cellular immune maker detection is available and credible, the expression of a single relatively nonspecific myeloid antigen as a immune maker to detect AUL or AUL associated with sarcoma is precise and effective in our case, which patient was benefit from HIA regiment.


Assuntos
Leucemia Mieloide Aguda , Leucemia , Sarcoma Mieloide , Humanos , Sarcoma Mieloide/diagnóstico , Sarcoma Mieloide/tratamento farmacológico , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Leucemia/diagnóstico , Medula Óssea/patologia , Doença Aguda , Azacitidina
17.
Nat Chem Biol ; 20(1): 83-92, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37857992

RESUMO

The inner mitochondrial membrane (IMM) generates power to drive cell function, and its dynamics control mitochondrial health and cellular homeostasis. Here, we describe the cell-permeant, lipid-like small molecule MAO-N3 and use it to assemble high-density environmentally sensitive (HIDE) probes that selectively label and image the IMM in live cells and multiple cell states. MAO-N3 pairs with strain-promoted azide-alkyne click chemistry-reactive fluorophores to support HIDE imaging using confocal, structured illumination, single-molecule localization and stimulated emission depletion microscopy, all with significantly improved resistance to photobleaching. These probes generate images with excellent spatial and temporal resolution, require no genetic manipulations, are non-toxic in model cell lines and primary cardiomyocytes (even under conditions that amplify the effects of mitochondrial toxins) and can visualize mitochondrial dynamics for 12.5 h. This probe will enable comprehensive studies of IMM dynamics with high temporal and spatial resolution.


Assuntos
Corantes Fluorescentes , Membranas Mitocondriais , Humanos , Células HeLa , Microscopia de Fluorescência/métodos , Lipídeos , Monoaminoxidase
18.
Sci China Life Sci ; 67(3): 504-517, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37930473

RESUMO

During the pathogenesis of type 1 diabetes (T1D) and type 2 diabetes (T2D), pancreatic islets, especially the ß cells, face significant challenges. These insulin-producing cells adopt a regeneration strategy to compensate for the shortage of insulin, but the exact mechanism needs to be defined. High-fat diet (HFD) and streptozotocin (STZ) treatment are well-established models to study islet damage in T2D and T1D respectively. Therefore, we applied these two diabetic mouse models, triggered at different ages, to pursue the cell fate transition of islet ß cells. Cre-LoxP systems were used to generate islet cell type-specific (α, ß, or δ) green fluorescent protein (GFP)-labeled mice for genetic lineage tracing, thereinto ß-cell GFP-labeled mice were tamoxifen induced. Single-cell RNA sequencing (scRNA-seq) was used to investigate the evolutionary trajectories and molecular mechanisms of the GFP-labeled ß cells in STZ-treated mice. STZ-induced diabetes caused extensive dedifferentiation of ß cells and some of which transdifferentiated into a or δ cells in both youth- and adulthood-initiated mice while this phenomenon was barely observed in HFD models. ß cells in HFD mice were expanded via self-replication rather than via transdifferentiation from α or δ cells, in contrast, α or δ cells were induced to transdifferentiate into ß cells in STZ-treated mice (both youth- and adulthood-initiated). In addition to the re-dedifferentiation of ß cells, it is also highly likely that these "α or δ" cells transdifferentiated from pre-existing ß cells could also re-trans-differentiate into insulin-producing ß cells and be beneficial to islet recovery. The analysis of ScRNA-seq revealed that several pathways including mitochondrial function, chromatin modification, and remodeling are crucial in the dynamic transition of ß cells. Our findings shed light on how islet ß cells overcome the deficit of insulin and the molecular mechanism of islet recovery in T1D and T2D pathogenesis.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Ilhotas Pancreáticas , Camundongos , Animais , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 1/genética , Ilhotas Pancreáticas/metabolismo , Células Secretoras de Insulina/metabolismo , Insulina/genética , Modelos Animais de Doenças , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia
19.
Int J Hyperthermia ; 41(1): 2297649, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38159561

RESUMO

Objective: Glioma constitutes the most common primary malignant tumor in the central nervous system. In recent years, microwave ablation (MWA) was expected to be applied in the minimally invasive treatment of brain tumors. This study aims to evaluate the feasibility and accuracy of microwave ablation in ex vivo brain tissue by Shear Wave Elastography (SWE) to explore the application value of real-time SWE in monitoring the process of MWA of brain tissue.Methods: Thirty ex vivo brain tissues were treated with different microwave power and ablation duration. The morphologic and microscopic changes of MWA tissues were observed, and the diameter of the ablation areas was measured. In this experiment, SWE is used to quantitatively evaluate brain tissue's degree of thermal injury immediately after ablation.Results: This study It is found that the ablation range measured by SWE after ablation is in good consistency with the pathological range [ICCSWEL1-L1 = 0.975(95% CI:0.959 - 0.985), ICCSWEL2-L2 = 0.887(95% CI:0.779 - 0.938)]. At the same time, the SWE value after ablation is significantly higher than before (mean ± SD,9.88 ± 2.64 kPa vs.23.6 ± 13.75 kPa; p < 0.001). In this study, the SWE value of tissues in different pathological states was further analyzed by the ROC curve (AUC = 0.86), and the threshold for distinguishing normal tissue from tissue after ablation was 13.7 kPa. The accuracy of evaluating ablation tissue using SWE can reach 84.72%, providing data support for real-time quantitative observation of the ablation range.Conclusion: In conclusion the accurate visualization and real-time evaluation of the organizational change range of the MWA process can be realized by real-time SWE.


Assuntos
Ablação por Cateter , Técnicas de Imagem por Elasticidade , Ablação por Radiofrequência , Suínos , Animais , Micro-Ondas/uso terapêutico , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia
20.
Eur J Med Chem ; 262: 115875, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37879169

RESUMO

Multiple myeloma (MM) is a common hematological malignancy. Although recent clinical applications of immunomodulatory drugs, proteasome inhibitors and CD38-targeting antibodies have significantly improved the outcome of MM patient with increased survival, the incidence of drug resistance and severe treatment-related complications is gradually on the rise. This review article summarizes the characteristics and clinical investigations of several MM drugs in clinical trials, including their structures, mechanisms of action, structure-activity relationships, and clinical study progress. Furthermore, the application potentials of the drugs that have not yet entered clinical trials are also reviewed. The review also outlines the future directions of MM drug development.


Assuntos
Neoplasias Hematológicas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Inibidores de Proteassoma/farmacologia , Inibidores de Proteassoma/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Neoplasias Hematológicas/tratamento farmacológico , Agentes de Imunomodulação
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