High-Efficiency in Vitro and in Vivo Detection of Zn2+ by Dye-Assembled Upconversion Nanoparticles

2015 ◽  
Vol 137 (6) ◽  
pp. 2336-2342 ◽  
Author(s):  
Juanjuan Peng ◽  
Wang Xu ◽  
Chai Lean Teoh ◽  
Sanyang Han ◽  
Beomsue Kim ◽  
...  
2019 ◽  
Vol 26 (12) ◽  
pp. 930-939 ◽  
Author(s):  
Rouhollah Vahabpour ◽  
Parya Basimi ◽  
Farzin Roohvand ◽  
Hassan Asadi ◽  
Gholnaz M. Irani ◽  
...  

Background: Supercharged GFP proteins were known as effective carriers for delivery of macromolecules into eukaryotic cells as well as fluorescent fusion tags for in vitro and in vivo detection. Objective: Herein, anti-viral effects of +36 GFP and its anti-tumor effects were studied in vitro and in vivo, respectively. Methods: We evaluated anti-HIV, anti-HSV, and anti-HCV effects of +36 GFP in vitro using ELISA, and real time PCR as common techniques for their detection, respectively. Moreover, we assessed the role of +36 GFP for eliciting HPV-related anti-tumor effects in mice due to the lack of HPV replication in vitro. Results: Our data showed that +36 GFP efficiently enter the cells and augment the transfection rate of HPV16E7 antigen, as well. Furthermore, +36 GFP significantly reduced HCV, HIV and HSV replication up to 75%, 49% and 43% in HCV-infected Huh7.5 cells, HIV-infected Hela cells and HSV-infected Vero cells, respectively. On the other hand, mice immunization with +36 GFP complexed with HPV16 E7 antigen (+36GFP + E7) or fused to HPV16 E7 antigen (+36GFP-E7) elicited a higher Th1 cellular immune response with the predominant IgG2a, IgG2b, IFN-γ and Granzyme B levels than those induced by other groups. These regimens protected mice against TC- 1 tumor challenge (~ 67%) compared to E7 protein alone (~ 33%). These data suggested that +36 GFP can act as an anti-viral agent at certain dose due to its high efficiency in cell penetration in vitro and in vivo. Conclusion: Generally, +36 GFP targets viral replication in vitro as well as helps to suppress the growth of HPV-related tumors in vivo.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jie Zheng ◽  
Na Tian ◽  
Fei Liu ◽  
Yidian Zhang ◽  
Jingfen Su ◽  
...  

AbstractIntraneuronal accumulation of hyperphosphorylated tau is a hallmark pathology shown in over twenty neurodegenerative disorders, collectively termed as tauopathies, including the most common Alzheimer’s disease (AD). Therefore, selectively removing or reducing hyperphosphorylated tau is promising for therapies of AD and other tauopathies. Here, we designed and synthesized a novel DEPhosphorylation TArgeting Chimera (DEPTAC) to specifically facilitate the binding of tau to Bα-subunit-containing protein phosphatase 2A (PP2A-Bα), the most active tau phosphatase in the brain. The DEPTAC exhibited high efficiency in dephosphorylating tau at multiple AD-associated sites and preventing tau accumulation both in vitro and in vivo. Further studies revealed that DEPTAC significantly improved microtubule assembly, neurite plasticity, and hippocampus-dependent learning and memory in transgenic mice with inducible overexpression of truncated and neurotoxic human tau N368. Our data provide a strategy for selective removal of the hyperphosphorylated tau, which sheds new light for the targeted therapy of AD and related-tauopathies.


2010 ◽  
Author(s):  
L. Sironi ◽  
S. Freddi ◽  
L. D'Alfonso ◽  
M. Collini ◽  
T. Gorletta ◽  
...  

2017 ◽  
Vol 89 (20) ◽  
pp. 11021-11026 ◽  
Author(s):  
Xinyue Song ◽  
Jiayu Zhang ◽  
Zihong Yue ◽  
Zonghua Wang ◽  
Zhihong Liu ◽  
...  

2000 ◽  
Vol 20 (21) ◽  
pp. 8059-8068 ◽  
Author(s):  
Chonghui Cheng ◽  
Stewart Shuman

ABSTRACT Topoisomerase IB catalyzes recombinogenic DNA strand transfer reactions in vitro and in vivo. Here we characterize a new pathway of topoisomerase-mediated DNA ligation in vitro (flap ligation) in which vaccinia virus topoisomerase bound to a blunt-end DNA joins the covalently held strand to a 5′ resected end of a duplex DNA containing a 3′ tail. The joining reaction occurs with high efficiency when the sequence of the 3′ tail is complementary to that of the scissile strand immediately 5′ of the cleavage site. A 6-nucleotide segment of complementarity suffices for efficient flap ligation. Invasion of the flap into the duplex apparently occurs while topoisomerase remains bound to DNA, thereby implying a conformational flexibility of the topoisomerase clamp around the DNA target site. The 3′ flap acceptor DNA mimics a processed end in the double-strand-break-repair recombination pathway. Our findings suggest that topoisomerase-induced breaks may be rectified by flap ligation, with ensuing genomic deletions or translocations.


2021 ◽  
Author(s):  
Yipu Wang ◽  
Dong Mei ◽  
Xinyi Zhang ◽  
Da-Hui Qu ◽  
Ju Mei ◽  
...  

With increase of social aging, Alzheimer's disease (AD) has been one of the serious diseases threatening human health. The occurrence of A<i>β </i>fibrils<i> </i>or plaques is recognized as the hallmark of AD.<i> </i>Currently, optical imaging has stood out to be a promising technique for the imaging of A<i>β</i> fibrils/plaques and the diagnosis of AD. However, restricted by their poor blood-brain barrier (BBB) penetrability, short-wavelength excitation and emission, and aggregation-caused quenching (ACQ) effect, the clinically used gold-standard optical probes such as <a>thioflavin</a> T (ThT) and thioflavin S (ThS), are not effective enough in the early diagnosis of AD <i>in vivo</i>. Herein, we put forward an “all-in-one” design principle and demonstrate its feasibility in developing high-performance fluorescent probes which are specific to A<i>β</i> fibrils/plaques and promising for super-early <i>in</i>-<i>vivo</i> diagnosis of AD. As a proof of concept, a simple rod-like amphiphilic NIR fluorescent AIEgen, i.e., AIE-CNPy-AD, is developed by taking the specificity, BBB penetration ability, deep-tissue penetration capacity, high signal-to-noise ratio (SNR) into consideration. AIE-CNPy-AD is constituted by connecting the electron-donating and accepting moieties through single bonds and tagging with a propanesulfonate tail, giving rise to the NIR fluorescence, aggregation-induced emission (AIE) effect, amphiphilicity, and rod-like structure, which in turn result in high binding-affinity and excellent specificity to A<i>β</i> fibrils/plaques, satisfactory ability to penetrate BBB and deep tissues, ultrahigh SNR and sensitivity, and high-fidelity imaging capability. <i>In-vitro, ex-vivo,</i> and <i>in-vivo</i> <a>identifying of A<i>β</i> fibrils/plaques</a> in different strains of mice indicate that AIE-CNPy-AD holds the universality to the detection of A<i>β</i> fibrils/plaques. It is noteworthy that AIE-CNPy-AD is even able to trace the small and sparsely distributed A<i>β</i> fibrils/plaques in very young AD model mice such as 4-month-old APP/PS1 mice which are reported to be the youngest mice to have A<i>β</i> deposits in brains, suggesting its great potential in diagnosis and intervention of AD at a super-early stage.


2015 ◽  
Vol 61 (1) ◽  
pp. 19-29 ◽  
Author(s):  
A.O. Shpakov ◽  
E.A. Shpakova

The regulation of signaling pathways involved in the control of many physiological functions is carried out via the heterotrimeric G protein-coupled receptors (GPCR). The search of effective and selective regulators of GPCR and intracellular signaling cascades coupled with them is one of the important problems of modern fundamental and clinical medicine. Recently data suggest that synthetic peptides and their derivatives, structurally corresponding to the intracellular and transmembrane regions of GPCR, can interact with high efficiency and selectivity with homologous receptors and influence, thus, the functional activity of intracellular signaling cascades and fundamental cellular processes controlled by them. GPCR-peptides are active in both in vitro and in vivo. They regulate hematopoiesis, angiogenesis and cell proliferation, inhibit tumor growth and metastasis, and prevent the inflammatory diseases and septic shock. These data show greatest prospects in the development of the new generations of drugs based on GPCR-derived peptides, capable of regulating the important functions of the organism.


2020 ◽  
Author(s):  
Lian Deng ◽  
Xiongjie Zhu ◽  
Zhongjian Yu ◽  
Ying Li ◽  
Lingyu Qin ◽  
...  

Abstract Although single-drug chemotherapy is still an effective treatment for esophageal cancer, its long-term application is limited by severe side effects. Nanomedicines have increasingly attracted attention because of their good biological safety, targeting and high-efficiency loading of multiple drugs. Herein, we have developed a pH-responsive nanocarrier that has high affinity for the transferrin receptor, which is overexpressed by tumor cells. The system is capable of simultaneous delivery of the chemotherapy drug, docetaxel, and the Chinese Medicine, curcumin, for treatment of esophageal cancer. This novel T7-modified targeting nanosystem releases loaded drugs when exposed to the acidic microenvironment of the tumor, and exerts a synergistic anti-tumor effect, and T7-NP-DC with docetaxel and curcumin loading of 10% and 6.1%, respectively. In vitro and in vivo studies showed that improved anti-tumor efficacy could be obtained by loading docetaxel and curcumin into the T7-modified nanocarrierwithout obvious toxicity or side effects, compared to drug without nanocarrier. Furthermore, the nanocarriers conjugated with T7 short peptides were more readily taken up by esophageal cancer cells compared with normal cells.Together, our findings indicate that the materials can safely exert synergistic anti-tumor effects and provide an excellent therapeutic platform for combination therapy of esophageal cancer.


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