scholarly journals High-performance Photoacoustic Probe for Biopsy-free Assessment of Copper Status in Murine Models of Wilson’s Disease and Liver Metastasis

2021 ◽  
Author(s):  
Melissa Lucero ◽  
Yuqi Tang ◽  
Chloe Zhang ◽  
ShengZhang Su ◽  
Joseph Forzano ◽  
...  
Keyword(s):  
Liver Metastasis ◽  
High Performance ◽  
Wilson’S Disease ◽  
Photoacoustic Imaging ◽  
Disease Model ◽  
Wilson's Disease ◽  
Copper Status ◽  
Metastasis Model ◽  
Healthy Control

<p>The development of high-performance photoacoustic (PA) probes that can monitor disease biomarkers in deep-tissue has the potential to replace invasive medical procedures such as a biopsy. However, such probes must be highly optimized for <i>in vivo</i> performance and exhibit an exceptional safety profile. In this study, we have developed PACu-1, the first PA probe designed for biopsy-free assessment (BFA) of hepatic Cu via photoacoustic imaging. PACu-1 features a Cu(I)-responsive trigger appended to an aza-BODIPY dye platform that has been optimized for ratiometric sensing. Owing to its excellent performance, we were able to detect basal levels of Cu in healthy wildtype mice, as well as elevated Cu in a Wilson’s disease model and in a liver metastasis model. To showcase the potential impact of PACu-1 for BFA, we conducted a blind study where we were able to successfully identify a Wilson’s disease animal from a group of healthy control mice with greater than 99.7% confidence.</p>

scholarly journals High-performance Photoacoustic Probe for Biopsy-free Assessment of Copper Status in Murine Models of Wilson’s Disease and Liver Metastasis

2021 ◽  
Author(s):  
Melissa Lucero ◽  
Yuqi Tang ◽  
Chloe Zhang ◽  
ShengZhang Su ◽  
Joseph Forzano ◽  
...  
Keyword(s):  
Liver Metastasis ◽  
High Performance ◽  
Wilson’S Disease ◽  
Photoacoustic Imaging ◽  
Disease Model ◽  
Wilson's Disease ◽  
Copper Status ◽  
Metastasis Model ◽  
Healthy Control

<p>The development of high-performance photoacoustic (PA) probes that can monitor disease biomarkers in deep-tissue has the potential to replace invasive medical procedures such as a biopsy. However, such probes must be highly optimized for <i>in vivo</i> performance and exhibit an exceptional safety profile. In this study, we have developed PACu-1, the first PA probe designed for biopsy-free assessment (BFA) of hepatic Cu via photoacoustic imaging. PACu-1 features a Cu(I)-responsive trigger appended to an aza-BODIPY dye platform that has been optimized for ratiometric sensing. Owing to its excellent performance, we were able to detect basal levels of Cu in healthy wildtype mice, as well as elevated Cu in a Wilson’s disease model and in a liver metastasis model. To showcase the potential impact of PACu-1 for BFA, we conducted a blind study where we were able to successfully identify a Wilson’s disease animal from a group of healthy control mice with greater than 99.7% confidence.</p>

Activity-based photoacoustic probe for biopsy-free assessment of copper in murine models of Wilson’s disease and liver metastasis

2021 ◽  
Vol 118 (36) ◽  
pp. e2106943118
Author(s):  
Melissa Y. Lucero ◽  
Yuqi Tang ◽  
Chloe J. Zhang ◽  
Shengzhang Su ◽  
Joseph A. Forzano ◽  
...  
Keyword(s):  
Liver Metastasis ◽  
High Performance ◽  
Wilson’S Disease ◽  
Photoacoustic Imaging ◽  
Disease Model ◽  
Wilson's Disease ◽  
Disease Biomarkers ◽  
Metastasis Model ◽  
Healthy Control

The development of high-performance photoacoustic (PA) probes that can monitor disease biomarkers in deep tissue has the potential to replace invasive medical procedures such as a biopsy. However, such probes must be optimized for in vivo performance and exhibit an exceptional safety profile. In this study, we have developed PACu-1, a PA probe designed for biopsy-free assessment (BFA) of hepatic Cu via photoacoustic imaging. PACu-1 features a Cu(I)-responsive trigger appended to an aza-BODIPY dye platform that has been optimized for ratiometric sensing. Owing to its excellent performance, we were able to detect basal levels of Cu in healthy wild-type mice as well as elevated Cu in a Wilson’s disease model and in a liver metastasis model. To showcase the potential impact of PACu-1 for BFA, we conducted two blind studies in which we were able to successfully identify Wilson’s disease animals from healthy control mice in each instance.

scholarly journals Altered diversity and composition of gut microbiota in Wilson's disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Xiangsheng Cai ◽  
Lin Deng ◽  
Xiaogui Ma ◽  
Yusheng Guo ◽  
Zhiting Feng ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Wilson’S Disease ◽  
Wilson's Disease ◽  
Healthy Individuals ◽  
Lower Abundance ◽  
Rrna Sequencing ◽  
Healthy Control ◽  
The Impact ◽  
Bacterial Groups

AbstractWilson’s disease (WD) is an autosomal recessive inherited disorder of chronic copper toxicosis with high mortality and disability. Recent evidence suggests a correlation between dysbiosis in gut microbiome and multiple diseases such as genetic and metabolic disease. However, the impact of intestinal microbiota polymorphism in WD have not been fully elaborated and need to be explore for seeking some microbiota benefit for WD patients. In this study, the 16S rRNA sequencing was performed on fecal samples from 14 patients with WD and was compared to the results from 16 healthy individuals. The diversity and composition of the gut microbiome in the WD group were significantly lower than those in healthy individuals. The WD group presented unique richness of Gemellaceae, Pseudomonadaceae and Spirochaetaceae at family level, which were hardly detected in healthy controls. The WD group had a markedly lower abundance of Actinobacteria, Firmicutes and Verrucomicrobia, and a higher abundance of Bacteroidetes, Proteobacteria, Cyanobacteria and Fusobacteria than that in healthy individuals. The Firmicutes to Bacteroidetes ratio in the WD group was significantly lower than that of healthy control. In addition, the functional profile of the gut microbiome from WD patients showed a lower abundance of bacterial groups involved in the host immune and metabolism associated systems pathways such as transcription factors and ABC-type transporters, compared to healthy individuals. These results implied dysbiosis of gut microbiota may be influenced by the host metabolic disorders of WD, which may provide a new understanding of the pathogenesis and new possible therapeutic targets for WD.

scholarly journals A novel BMI-1 inhibitor QW24 for the treatment of stem-like colorectal cancer

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Jinhua Wang ◽  
Yajing Xing ◽  
Yingying Wang ◽  
Yundong He ◽  
Liting Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Liver Metastasis ◽  
Tumor Growth ◽  
Cell Lines ◽  
Xenograft Model ◽  
Proliferation Assay ◽  
Self Renewal ◽  
Metastasis Model

Abstract Background Cancer-initiating cell (CIC), a functionally homogeneous stem-like cell population, is resonsible for driving the tumor maintenance and metastasis, and is a source of chemotherapy and radiation-therapy resistance within tumors. Targeting CICs self-renewal has been proposed as a therapeutic goal and an effective approach to control tumor growth. BMI-1, a critical regulator of self-renewal in the maintenance of CICs, is identified as a potential target for colorectal cancer therapy. Methods Colorectal cancer stem-like cell lines HCT116 and HT29 were used for screening more than 500 synthetic compounds by sulforhodamine B (SRB) cell proliferation assay. The candidate compound was studied in vitro by SRB cell proliferation assay, western blotting, cell colony formation assay, quantitative real-time PCR, flow cytometry analysis, and transwell migration assay. Sphere formation assay and limiting dilution analysis (LDA) were performed for measuring the effect of compound on stemness properties. In vivo subcutaneous tumor growth xenograft model and liver metastasis model were performed to test the efficacy of the compound treatment. Student’s t test was applied for statistical analysis. Results We report the development and characterization of a small molecule inhibitor QW24 against BMI-1. QW24 potently down-regulates BMI-1 protein level through autophagy-lysosome degradation pathway without affecting the BMI-1 mRNA level. Moreover, QW24 significantly inhibits the self-renewal of colorectal CICs in stem-like colorectal cancer cell lines, resulting in the abrogation of their proliferation and metastasis. Notably, QW24 significantly suppresses the colorectal tumor growth without obvious toxicity in the subcutaneous xenograft model, as well as decreases the tumor metastasis and increases mice survival in the liver metastasis model. Moreover, QW24 exerts a better efficiency than the previously reported BMI-1 inhibitor PTC-209. Conclusions Our preclinical data show that QW24 exerts potent anti-tumor activity by down-regulating BMI-1 and abrogating colorectal CICs self-renewal without obvious toxicity in vivo, suggesting that QW24 could potentially be used as an effective therapeutic agent for clinical colorectal cancer treatment.

Effects of copper metabolism on neurological functions in Wistar and Wilson’s disease model rats

2006 ◽  
Vol 349 (3) ◽  
pp. 1079-1086 ◽  
Author(s):  
Noriko Fujiwara ◽  
Hiroyuki Iso ◽  
Nobue Kitanaka ◽  
Junichi Kitanaka ◽  
Hironobu Eguchi ◽  
...  
Keyword(s):  
Wilson’S Disease ◽  
Disease Model ◽  
Copper Metabolism ◽  
Wilson's Disease

scholarly journals Pillar[5]arene-Modified Gold Nanorods as Nanocarriers for Multi-Modal Imaging-Guided Synergistic Photodynamic-Photothermal Therapy

2020 ◽  
Author(s):  
Nan Song ◽  
Zhijun Zhang ◽  
Peiying Liu ◽  
Dihua Dai ◽  
Chao Chen ◽  
...  
Keyword(s):  
Photothermal Therapy ◽  
High Performance ◽  
Tumor Imaging ◽  
Photoacoustic Imaging ◽  
Functional Materials ◽  
Ros Generation ◽  
Cancer Therapies ◽  
New Strategy

Supramolecular approaches have opened up vast possibilities in the construction of versatile functional materials, especially those with stimuli-responsiveness and integrated functionalities of multi-modal diagnosis and synergistic therapeutics. In this study, a hybrid theranostic nanosystem named TTPY-PyÌCP5@AuNR is constructed via facile host-guest interactions, where TTPY-Py is a photosensitizer with aggregation-induced emission and CP5@AuNR represents the carboxylatopillar[5]arene (CP5)-modified Au nanorods. TTPY-PyÌCP5@AuNR integrates the respective advantages of TTPY-Py and CP5@AuNR such as the high performance of reactive oxygen species (ROS) generation and photothermal conversion, and meanwhile shows fluorescence responses to both temperature and pH stimuli due to the non-covalent interactions. The successful modification of CP5 macrocycles on AuNRs surfaces can eliminate the cytotoxicity of AuNRs and enable them to serve as the nanocarrier of TTPY-Py for further theranostic application. Significantly, both in vitro and in vivo evaluations demonstrate that this supramolecular nanotheranostic system possesses multiple phototheranostic modalities including intensive fluorescence imaging (FLI), photoacoustic imaging (PAI), efficient photodynamic therapy (PDT), and photothermal therapy (PTT), indicating its great potentials for FLI-PAI imaging-guided synergistic PDT-PTT therapy. Besides, TTPY-Py can be released from the nanocarriers upon activating by the acidic environment of lysosomes and then specifically light up mitochondria. This study brings up a new strategy into the design of versatile nanotheranostics for accurate tumor imaging and cancer therapies.

Sign in / Sign up

Export Citation Format

Share Document