scholarly journals Therapeutic Application of Genetically Engineered Ribosome-Inactivating Toxin Proteins for Cancer

2021 ◽  
Vol 2 (12) ◽  
pp. 1216-1228
Author(s):  
Safir Ullah Khan ◽  
Munir Ullah Khan

Recently, Ribosome-Inactivating Proteins (RIPs) as a class of anticancer medicines have garnered considerable attention due to their novel anticancer mechanism. Although the medications are small, RIPs utilize the Large-Size Effect (LSE) to block the efflux procedure that are regulated through Drug Resistance Transporters (DRTs), and protect host cells from drug transfection. There are many significant challenges for their therapeutic applications that seriously restrict their usefulness, particularly their strategy towards tumor cells. The primary objective of this review is to emphasize Trichosanthin (TCS) along with Gelonin (Gel) and additional types of RIPs, particularly scorpion venom-derived RIPs, to demonstrate that they should be grappling through what kinds of bio-barriers to overcome in cancer therapeutic science. Next, we will emphasize the latest state-of-the-art in providing cancer treatment RIPs.

1984 ◽  
Vol 79 ◽  
pp. 607-616
Author(s):  
R. R. Shannon

The requirements on gratings and coatings for astronomical use differ from the general industrial requirements primarily in the scale of the components to be fabricated. Telescopes have large primary mirrors which require large coating plants to handle the components. Dispersive elements are driven by the requirement to be efficient in the presence of large working apertures, and usually optimize to large size in order to efficiently use the incoming radiation. Beyond this, there is a “new” technology of direct electronic sensors that places specific limits upon the image scale that can be used at the output of a telescope system, whether direct imagery or spectrally divided imagery is to be examined. This paper will examine the state of the art in these areas and suggest some actions and decisions that will be required in order to apply current technology to the predicted range of large new telescopes.


2021 ◽  
pp. 095605992110640
Author(s):  
Hemant Arora ◽  
Rutvik Dangarwala ◽  
Sudipto Mukherjee ◽  
Bhavdeep Singh Munjal

Space exploration arises the demand for launching large size structures to satisfy the need of high bandwidth telecommunication, earth observation and deep space interplanetary missions. Launching of these monolithic structures of sizes 3 m or more are not feasible due to limited launch fairing space of state-of-the-art launch vehicles. Therefore, the development of innovative deployment mechanisms is need of the hour. Deployment process of space borne deployable systems is the process of transition from mechanism to structure which is one of the unreliable stage due to existence of many conventional rotary joints which causes loss of energy due to backlash, friction and misalignment. An investigation study is presented in this paper for churning out a solution of flexible hinges using tape springs in state-of-the-art space deployable configurations which eliminates the factors causing loss of energy. Analytical and experimental methods are evaluated for investigating the bending behaviour of tape flexures. Tape flexures demonstrate to be a suitable candidate for compliant deployable configuration. The proposed configuration with combination of two tape flexures mounted in such a way that concave curve of each tape faces each other are structurally analysed for desired rotation angle. A comparison study is carried out for various material options of single and double layered tape flexures proposed for a flexure hinge. Practical feasibility of the proposed configuration is also demonstrated successfully on space borne deployable structures.


Nanoscale ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 611-621 ◽  
Author(s):  
Ya Chang ◽  
Shuo Yao ◽  
Yifang Chen ◽  
Jingjing Huang ◽  
Aihua Wu ◽  
...  

A SHEATH strategy was developed to overcome the delivery barrier against drug development and the clinical application of the cytoplasmic active proteins (e.g., ribosome-inactivating proteins, RIPs).


2020 ◽  
Vol 117 (44) ◽  
pp. 27141-27147 ◽  
Author(s):  
Lang Rao ◽  
Shuai Xia ◽  
Wei Xu ◽  
Rui Tian ◽  
Guocan Yu ◽  
...  

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the urgent need to rapidly develop therapeutic strategies for such emerging viruses without effective vaccines or drugs. Here, we report a decoy nanoparticle against COVID-19 through a powerful two-step neutralization approach: virus neutralization in the first step followed by cytokine neutralization in the second step. The nanodecoy, made by fusing cellular membrane nanovesicles derived from human monocytes and genetically engineered cells stably expressing angiotensin converting enzyme II (ACE2) receptors, possesses an antigenic exterior the same as source cells. By competing with host cells for virus binding, these nanodecoys effectively protect host cells from the infection of pseudoviruses and authentic SARS-CoV-2. Moreover, relying on abundant cytokine receptors on the surface, the nanodecoys efficiently bind and neutralize inflammatory cytokines including interleukin 6 (IL-6) and granulocyte−macrophage colony-stimulating factor (GM-CSF), and significantly suppress immune disorder and lung injury in an acute pneumonia mouse model. Our work presents a simple, safe, and robust antiviral nanotechnology for ongoing COVID-19 and future potential epidemics.


2017 ◽  
Vol 32 (10) ◽  
pp. 1833-1847 ◽  
Author(s):  
Sascha Nowak ◽  
Martin Winter

Being successfully introduced into the market only 25 years ago, lithium ion batteries are already state-of-the-art power sources for portable electronic devices and the most promising candidate for energy storage in large-size batteries. Therefore, elemental analysis of lithium ion batteries (lithium ion batteries), their components and decomposition products is a fast growing topic in the literature.


2020 ◽  
Author(s):  
Jayesh Arun Bafna ◽  
Eulàlia Sans-Serramitjana ◽  
Silvia Acosta-Gutiérrez ◽  
Igor Bodrenko ◽  
Daniel Hörömpöli ◽  
...  

<p>Despite decades of therapeutic application of aminoglycosides, it is still a matter of debate if porins contribute to the translocation of the antibiotics across the bacterial outer membrane. Here, we quantified the uptake of kanamycin across the major porin channels OmpF and OmpC present in the outer membrane of <i>E. coli.</i> Our analysis revealed that, despite its relatively large size, about 10 - 20 kanamycin molecules per second permeate through OmpF and OmpC under a 10 mM concentration gradient, whereas OmpN does not allow the passage. Molecular simulations elucidate the uptake mechanism of kanamycin through these porins. Whole-cell studies with a decisive set of <i>E. coli</i> porin mutants provide evidence that translocation of kanamycin <i>via</i> porins is relevant for antibiotic potency.</p>


2020 ◽  
Author(s):  
Jayesh Arun Bafna ◽  
Eulàlia Sans-Serramitjana ◽  
Silvia Acosta-Gutiérrez ◽  
Igor Bodrenko ◽  
Daniel Hörömpöli ◽  
...  

<p>Despite decades of therapeutic application of aminoglycosides, it is still a matter of debate if porins contribute to the translocation of the antibiotics across the bacterial outer membrane. Here, we quantified the uptake of kanamycin across the major porin channels OmpF and OmpC present in the outer membrane of <i>E. coli.</i> Our analysis revealed that, despite its relatively large size, about 10 - 20 kanamycin molecules per second permeate through OmpF and OmpC under a 10 mM concentration gradient, whereas OmpN does not allow the passage. Molecular simulations elucidate the uptake mechanism of kanamycin through these porins. Whole-cell studies with a decisive set of <i>E. coli</i> porin mutants provide evidence that translocation of kanamycin <i>via</i> porins is relevant for antibiotic potency.</p>


Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 400 ◽  
Author(s):  
Franziska Woelfl ◽  
Psylvia Léger ◽  
Nadia Oreshkova ◽  
Felix Pahmeier ◽  
Stefan Windhaber ◽  
...  

The sand fly-borne Toscana virus (TOSV) is the major cause of human meningoencephalitis in the Mediterranean basin during the summer season. In this work, we have developed a T7 RNA polymerase-driven reverse genetics system to recover infectious particles of a lineage B strain of TOSV. The viral protein pattern and growth properties of the rescued virus (rTOSV) were found to be similar to those of the corresponding wild-type (wt) virus. Using this system, we genetically engineered a TOSV mutant lacking expression of the non-structural protein NSs (rTOSVɸNSs). Unlike rTOSV and the wt virus, rTOSVɸNSs was unable to (i) suppress interferon (IFN)-b messenger RNA induction; and (ii) grow efficiently in cells producing IFN-b. Together, our results highlight the importance of NSs for TOSV in evading the IFN response and provide a comprehensive toolbox to investigate the TOSV life cycle in mammalian and insect host cells, including several novel polyclonal antibodies.


2020 ◽  
Vol 21 (17) ◽  
pp. 6435
Author(s):  
Hosanna Brave ◽  
Ronan MacLoughlin

Respiratory and pulmonary diseases are among the leading causes of death globally. Despite tremendous advancements, there are no effective pharmacological therapies capable of curing diseases such as COPD (chronic obstructive pulmonary disease), ARDS (acute respiratory distress syndrome), and COVID-19. Novel and innovative therapies such as advanced therapy medicinal products (ATMPs) are still in early development. However, they have exhibited significant potential preclinically and clinically. There are several longitudinal studies published, primarily focusing on the use of cell therapies for respiratory diseases due to their anti-inflammatory and reparative properties, thereby hinting that they have the capability of reducing mortality and improving the quality of life for patients. The primary objective of this paper is to set out a state of the art review on the use of aerosolized MSCs and their potential to treat these incurable diseases. This review will examine selected respiratory and pulmonary diseases, present an overview of the therapeutic potential of cell therapy and finally provide insight into potential routes of administration, with a focus on aerosol-mediated ATMP delivery.


2014 ◽  
Vol 89 (3) ◽  
pp. 1932-1938 ◽  
Author(s):  
Dinesh Jaishankar ◽  
Abraam M. Yakoub ◽  
Anita Bogdanov ◽  
Tibor Valyi-Nagy ◽  
Deepak Shukla

Uncontrolled herpes simplex virus 1 (HSV-1) infection can advance to serious conditions, including corneal blindness or fatal encephalitis. Here, we describe a highly potent anti-HSV-1 peptide (DG2) that inhibits HSV-1 entry into host cells and blocks all aspects of infection. Importantly, DG2 is highly resistant to proteases and shows minimal toxicity, paving the way for prophylactic or therapeutic application of the peptidein vivo.


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