scholarly journals Protection of pancreatic islets using theranostic silencing nanoparticles in a baboon model of islet transplantation

2020 ◽  
Author(s):  
Ada Admin ◽  
Thomas Pomposelli ◽  
Ping Wang ◽  
Kazuhiro Takeuchi ◽  
Katsunori Miyake ◽  
...  
Keyword(s):  
Islet Transplantation ◽  
In Vivo Studies ◽  
Pancreatic Islet Transplantation ◽  
Insulin Requirements ◽  
Novel Approach ◽  
Apoptotic Effect ◽  
Novel Strategy ◽  
Interfering Rna

The long-term success of pancreatic islet transplantation (Tx) as a cure for type 1 diabetes remains limited. Islet loss after Tx related to apoptosis, inflammation and other factors continues to limit its efficacy. In this project we demonstrate a novel approach aimed at protection of islets prior to Tx in non-human primates (NHP, baboons) by silencing a gene (caspase 3) responsible for induction of apoptosis. This was done using small interfering RNA (siRNA, siCas-3) conjugated to magnetic nanoparticles (MN). In addition to serving as carriers for siCas-3 these nanoparticles also act as reporters for magnetic resonance imaging so islets labeled with MN-siCas-3 can be monitored in vivo after Tx. In vitro studies showed the anti-apoptotic effect of MN-siCas-3 on islets in culture resulting in a minimal islet loss. For in vivo studies donor baboon islets were labeled with MN-siCas-3 and infused into recipient diabetic subjects. A dramatic reduction in insulin requirements was observed in animals transplanted even with a marginal number of labeled islets compared to controls. By demonstrating the protective effect of MN-siCas-3 in the challenging NHP model, this study proposes a novel strategy to minimize the number of donor islets required from either cadaver or living donor.

scholarly journals Protection of pancreatic islets using theranostic silencing nanoparticles in a baboon model of islet transplantation

2020 ◽  
Author(s):  
Ada Admin ◽  
Thomas Pomposelli ◽  
Ping Wang ◽  
Kazuhiro Takeuchi ◽  
Katsunori Miyake ◽  
...  
Keyword(s):  
Islet Transplantation ◽  
In Vivo Studies ◽  
Pancreatic Islet Transplantation ◽  
Insulin Requirements ◽  
Novel Approach ◽  
Apoptotic Effect ◽  
Novel Strategy ◽  
Interfering Rna

The long-term success of pancreatic islet transplantation (Tx) as a cure for type 1 diabetes remains limited. Islet loss after Tx related to apoptosis, inflammation and other factors continues to limit its efficacy. In this project we demonstrate a novel approach aimed at protection of islets prior to Tx in non-human primates (NHP, baboons) by silencing a gene (caspase 3) responsible for induction of apoptosis. This was done using small interfering RNA (siRNA, siCas-3) conjugated to magnetic nanoparticles (MN). In addition to serving as carriers for siCas-3 these nanoparticles also act as reporters for magnetic resonance imaging so islets labeled with MN-siCas-3 can be monitored in vivo after Tx. In vitro studies showed the anti-apoptotic effect of MN-siCas-3 on islets in culture resulting in a minimal islet loss. For in vivo studies donor baboon islets were labeled with MN-siCas-3 and infused into recipient diabetic subjects. A dramatic reduction in insulin requirements was observed in animals transplanted even with a marginal number of labeled islets compared to controls. By demonstrating the protective effect of MN-siCas-3 in the challenging NHP model, this study proposes a novel strategy to minimize the number of donor islets required from either cadaver or living donor.

scholarly journals Role of Exosomes in Islet Transplantation

2021 ◽  
Vol 12 ◽  
Author(s):  
Jordan Mattke ◽  
Srividya Vasu ◽  
Carly M. Darden ◽  
Kenjiro Kumano ◽  
Michael C. Lawrence ◽  
...  
Keyword(s):  
Islet Transplantation ◽  
Graft Function ◽  
Pancreatic Islet Transplantation ◽  
Complex Molecules ◽  
Wide Range ◽  
And Function ◽  
Antigen Presenting

Exosomes are known for their ability to transport nucleic acid, lipid, and protein molecules, which allows for communication between cells and tissues. The cargo of the exosomes can have a variety of effects on a wide range of targets to mediate biological function. Pancreatic islet transplantation is a minimally invasive cell replacement therapy to prevent or reverse diabetes mellitus and is currently performed in patients with uncontrolled type 1 diabetes or chronic pancreatitis. Exosomes have become a focus in the field of islet transplantation for the study of diagnostic markers of islet cell viability and function. A growing list of miRNAs identified from exosomes collected during the process of isolating islets can be used as diagnostic biomarkers of islet stress and damage, leading to a better understanding of critical steps of the isolation procedure that can be improved to increase islet yield and quality. Exosomes have also been implicated as a possible contributor to islet graft rejection following transplantation, as they carry donor major histocompatibility complex molecules, which are then processed by recipient antigen-presenting cells and sensed by the recipient immune cells. Exosomes may find their way into the therapeutic realm of islet transplantation, as exosomes isolated from mesenchymal stem cells have shown promising results in early studies that have seen increased viability and functionality of isolated and grafted islets in vitro as well as in vivo. With the study of exosomes still in its infancy, continued research on the role of exosomes in islet transplantation will be paramount to understanding beta cell regeneration and improving long-term graft function.

scholarly journals Scrophulariae Radix: An Overview of Its Biological Activities and Nutraceutical and Pharmaceutical Applications

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5250
Author(s):  
Hae-Jin Lee ◽  
Hae-Lim Kim ◽  
Dong-Ryung Lee ◽  
Bong-Keun Choi ◽  
Seung-Hwan Yang
Keyword(s):  
Biological Activities ◽  
Neuroprotective Effect ◽  
In Vivo Studies ◽  
Amnesic Effect ◽  
In Vivo Experiments ◽  
Toxicological Studies ◽  
Apoptotic Effect ◽  
Pharmaceutical Industries

Scrophulariae Radix (SR) has an important role as a medicinal plant, the roots of which are recorded used to cure fever, swelling, constipation, pharyngitis, laryngitis, neuritis, sore throat, rheumatism, and arthritis in Asia for more than two thousand years. In this paper, the studies published on Scrophularia buergeriana (SB) and Scrophularia ningpoensis (SN) in the latest 20 years were reviewed, and the biological activities of SB and SN were evaluated based on in vitro and in vivo studies. SB presented anti-inflammatory activities, immune-enhancing effects, bone disorder prevention activity, neuroprotective effect, anti-amnesic effect, and anti-allergic effect; SN showed a neuroprotective effect, anti-apoptotic effect, anti-amnesic effect, and anti-depressant effect; and SR exhibited an immune-enhancing effect and cardioprotective effects through in vitro and in vivo experiments. SB and SN are both known to exert neuroprotective and anti-amensice effects. This review investigated their applicability in the nutraceutical, functional foods, and pharmaceutical industries. Further studies, such as toxicological studies and clinical trials, on the efficacy and safety of SR, including SB and SN, need to be conducted.

scholarly journals Scolicidal and Apoptotic Activities of 5-hydroxy-1, 4-naphthoquinone as a Potent Agent against Echinococcus granulosus Protoscoleces

2021 ◽  
Vol 14 (7) ◽  
pp. 623
Author(s):  
Masoud Moghadaszadeh ◽  
Mehdi Khayyati ◽  
Adel Spotin ◽  
Roghayeh Norouzi ◽  
Abdol Sattar Pagheh ◽  
...  
Keyword(s):  
Echinococcus Granulosus ◽  
Public Health Problem ◽  
In Vivo Studies ◽  
Cystic Hydatid Disease ◽  
Liposomal System ◽  
Physico Chemical ◽  
Apoptotic Effect ◽  
Apoptotic Activity

Cystic hydatid disease (CHD) is a zoonotic disease with different clinical stages caused by the larval stage of the cestode Echinococcus granulosus. It is important to highlight as a public health problem in various regions of the world. In the current study, the efficacy and apoptotic activity of the liposomal system containing juglone (5-hydroxy-1,4-naphthoquinone) were assessed against protoscoleces (PSCs) in vitro. To this aim, firstly, liposomal vesicles were prepared by the thin-film method. Their physico-chemical features were assessed using Zeta-Sizer and Scanning Electron Microscope (SEM). Subsequently, various concentrations (50, 100, 200, 400, and 800 μg/mL) of juglone nanoliposomes at different exposure times (15, 30, 60, and 120 min) were used against PSCs. Results showed that juglone nanoliposomes at all tested concentrations induced scolicidal effect, however, 800 μg/mL and 400 μg/mL of juglone nanoliposomes could reach 100% mortality in 60 and 120 min, respectively. Additionally, we found that caspase-3 mRNA expression was higher in PSCs treated with juglone nanoliposomes compared to control groups (p < 0.001). Therefore, juglone nanoliposomes are suggested to have a more potent apoptotic effect on PSCs. Generally, optimized doses of juglone nanoliposomes could display significant scolicidal effects. Moreover, further in vivo studies are required to evaluate the efficacy of this nanoliposome.

scholarly journals Selenophosphate synthetase 2 is essential for selenoprotein biosynthesis

2007 ◽  
Vol 404 (1) ◽  
pp. 115-120 ◽  
Author(s):  
Xue-Ming Xu ◽  
Bradley A. Carlson ◽  
Robert Irons ◽  
Heiko Mix ◽  
Nianxin Zhong ◽  
...  
Keyword(s):  
Small Interfering Rna ◽  
Essential Role ◽  
In Vitro Studies ◽  
In Vivo Studies ◽  
Nih3t3 Cells ◽  
Selenophosphate Synthetase ◽  
Interfering Rna

Selenophosphate synthetase (SelD) generates the selenium donor for selenocysteine biosynthesis in eubacteria. One homologue of SelD in eukaryotes is SPS1 (selenophosphate synthetase 1) and a second one, SPS2, was identified as a selenoprotein in mammals. Earlier in vitro studies showed SPS2, but not SPS1, synthesized selenophosphate from selenide, whereas SPS1 may utilize a different substrate. The roles of these enzymes in selenoprotein synthesis in vivo remain unknown. To address their function in vivo, we knocked down SPS2 in NIH3T3 cells using small interfering RNA and found that selenoprotein biosynthesis was severely impaired, whereas knockdown of SPS1 had no effect. Transfection of SPS2 into SPS2 knockdown cells restored selenoprotein biosynthesis, but SPS1 did not, indicating that SPS1 cannot complement SPS2 function. These in vivo studies indicate that SPS2 is essential for generating the selenium donor for selenocysteine biosynthesis in mammals, whereas SPS1 probably has a more specialized, non-essential role in selenoprotein metabolism.

scholarly journals Tritium labeling of antisense oligonucleotides via different conjugation agents

AAPS Open ◽  
2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Martin R. Edelmann ◽  
Christophe Husser ◽  
Martina B. Duschmalé ◽  
Guy Fischer ◽  
Claudia Senn ◽  
...  
Keyword(s):  
Antisense Oligonucleotides ◽  
Specific Activity ◽  
Plasma Concentrations ◽  
In Vivo Studies ◽  
Radioactive Label ◽  
Target Interaction ◽  
Time Profiles ◽  
Novel Approach

AbstractA novel approach to tritium-labeled antisense oligonucleotides (ASO) was established by conjugating N-succinimidyl propionate, as well as maleimide-derivatives, to the 3′-end of ASOs targeting metastasis-associated lung adenocarcinoma transcript 1 (Malat1) containing amino- or sulfhydryl-linkers. In vitro stability and Malat1 RNA reduction studies demonstrated that N-ethylmaleimide (NEM) could be used as a stable tag while maintaining the desired target interaction. The corresponding radioactive label conjugation using [3H]-NEM resulted in tritium-labeled ASOs with a high molar specific activity of up to 17 Ci/mmol. Single-dose in vivo studies in mice were carried out to compare [3H]-ASOs with their unlabeled counterpart ASOs, with and without conjugation to N-acetylgalactosamine (GalNAc), for tissue and plasma concentrations time profiles. Despite the structural modification of the labeled ASOs, in vitro target interaction and in vivo pharmacokinetic behaviors were similar to that of the unlabeled ASOs. In conclusion, this new method provides a powerful technique for fast and safe access to tritium-labeled oligonucleotides, e.g., for pharmacokinetic, mass balance, or autoradiography studies. Graphical abstract

Synthesis, characterization and evaluation of collagen scaffolds crosslinked with aminosilane functionalized silver nanoparticles: in vitro and in vivo studies

2015 ◽  
Vol 3 (15) ◽  
pp. 3032-3043 ◽  
Author(s):  
Abhishek Mandal ◽  
Santhanam Sekar ◽  
N. Chandrasekaran ◽  
Amitava Mukherjee ◽  
Thotapalli P. Sastry
Keyword(s):  
Silver Nanoparticles ◽  
Clinical Applications ◽  
In Vivo Studies ◽  
Cross Linking ◽  
Collagen Scaffolds ◽  
Novel Approach

This work presents a novel approach for functionalization of silver nanoparticles and cross-linking them with collagen to form FSCSC scaffolds suitable for clinical applications.

scholarly journals Dextran-Curcumin Nanosystems Inhibit Cell Growth and Migration Regulating the Epithelial to Mesenchymal Transition in Prostate Cancer Cells

2021 ◽  
Vol 22 (13) ◽  
pp. 7013
Author(s):  
Emilia Bevacqua ◽  
Manuela Curcio ◽  
Federica Saletta ◽  
Orazio Vittorio ◽  
Giuseppe Cirillo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
In Vivo Studies ◽  
Ros Production ◽  
Cell Growth And Migration ◽  
Mesenchymal Transition ◽  
Curcumin Nanoparticles ◽  
Apoptotic Effect

Functional nanocarriers which are able to simultaneously vectorize drugs to the site of interest and exert their own cytotoxic activity represent a significant breakthrough in the search for effective anticancer strategies with fewer side effects than conventional chemotherapeutics. Here, we propose previously developed, self-assembling dextran-curcumin nanoparticles for the treatment of prostate cancer in combination therapy with Doxorubicin (DOXO). Biological effectiveness was investigated by evaluating the cell viability in either cancer and normal cells, reactive oxygen species (ROS) production, apoptotic effect, interference with the cell cycle, and the ability to inhibit cell migration and reverse the epithelial to mesenchymal transition (EMT). The results proved a significant enhancement of curcumin efficiency upon immobilization in nanoparticles: IC50 reduced by a half, induction of apoptotic effect, and improved ROS production (from 67 to 134%) at low concentrations. Nanoparticles guaranteed a pH-dependent DOXO release, with a more efficient release in acidic environments. Finally, a synergistic effect between nanoparticles and Doxorubicin was demonstrated, with the free curcumin showing additive activity. Although in vivo studies are required to support the findings of this study, these preliminary in vitro data can be considered a proof of principle for the design of an effective therapy for prostate cancer treatment.

Sign in / Sign up

Export Citation Format

Share Document