scholarly journals Chloroquine and Lopinavir (COVID-19 Drug Candidates) Signal Amplification by Reversible Exchange

Author(s):  
HyeJin Jeong ◽  
Sein Min ◽  
Heelim Chae ◽  
Sara Kim ◽  
Gunwoo Lee ◽  
...  

<p>To overcome the recent coronavirus pneumonia (COVID-19), several drug candidates are suggested and tested for the latest clinical treatment. Chloroquine and lopinavir are showing definite effects after treatment. To understand more about those roles in molecular level and future application on NMR/MRI, hyperpolarization technique can open new opportunities in the diagnosis and biomedical researches to cope with COVID-19. SABRE-based hyperpolarization studies on those two drug candidates are carried out and we observed hyperpolarized proton signals from the whole structures, which can be possible by unprecedented long-distance polarization transfer by <i>para</i>-hydrogen. Base on this result, future work on isotope labeling, and further polarization transfer on long T1 time nuclei including clinical perspectives will open a new door for overcoming this dreadful catastrophe.</p>

Author(s):  
HyeJin Jeong ◽  
Sein Min ◽  
Heelim Chae ◽  
Sara Kim ◽  
Gunwoo Lee ◽  
...  

<p></p><p>Several drug candidates have been proposed and tested as the latest clinical treatment for the coronavirus pneumonia (COVID-19). Chloroquine, hydroxychloroquine, ritonavir/lopinavir, and favipiravir are proved to be effective after treatment. The hyperpolarization technique presents an ability to further understand the roles of these drugs at the molecular scale and applications in nuclear magnetic resonance/magnetic resonance imaging (NMR/MRI). This technique may provide new opportunities in diagnosis and biomedical research to cope with COVID-19. Signal amplification by reversible exchange (SABRE)-based hyperpolarization studies on large-sized drug candidates were carried out. We observed hyperpolarized proton signals from whole structures, due to the unprecedented long-distance polarization transfer by <i>para</i>-hydrogen. We also found that the optimum magnetic field for the maximum polarization transfer yield was dependent on the molecular structure. Therefore, future research on isotope labelling and polarization transfer on long T1 time nuclei including clinical perspectives can help us overcome this worldwide pandemic.</p><p></p>


2020 ◽  
Author(s):  
HyeJin Jeong ◽  
Sein Min ◽  
Heelim Chae ◽  
Sara Kim ◽  
Gunwoo Lee ◽  
...  

<p></p><p>Several drug candidates have been proposed and tested as the latest clinical treatment for the coronavirus pneumonia (COVID-19). Chloroquine, hydroxychloroquine, ritonavir/lopinavir, and favipiravir are proved to be effective after treatment. The hyperpolarization technique presents an ability to further understand the roles of these drugs at the molecular scale and applications in nuclear magnetic resonance/magnetic resonance imaging (NMR/MRI). This technique may provide new opportunities in diagnosis and biomedical research to cope with COVID-19. Signal amplification by reversible exchange (SABRE)-based hyperpolarization studies on large-sized drug candidates were carried out. We observed hyperpolarized proton signals from whole structures, due to the unprecedented long-distance polarization transfer by <i>para</i>-hydrogen. We also found that the optimum magnetic field for the maximum polarization transfer yield was dependent on the molecular structure. Therefore, future research on isotope labelling and polarization transfer on long T1 time nuclei including clinical perspectives can help us overcome this worldwide pandemic.</p><p></p>


Nanomedicine ◽  
2021 ◽  
Author(s):  
Muhammad Ikram ◽  
Bilal Javed ◽  
Syed Wajeeh Ul Hassan ◽  
Seema Hassan Satti ◽  
Abdullah Sarwer ◽  
...  

Biogenic titanium dioxide nanoparticles have unique size, shape and biochemical functional corona that embellish them with the potential to perform therapeutic actions such as anticancer, antimicrobial, antioxidant, larvicidal and photocatalysis by adopting various mechanistic or physiological approaches at the molecular level. We have provided a detailed overview of some of these physiological mechanisms, including disruption of the electron transport chain, DNA fragmentation, mitochondrial damage, induction of apoptosis, disorganization of the plasma membrane, inhibition of ATP synthase activity, suspension of cellular signaling pathways and inhibition of enzymatic activity. The biogenic synthesis of customized titanium dioxide nanoparticles has future application potentials to do breakthroughs in the pharmaceutical sectors to advance precision medicine and to better explain the disease prognosis and treatment strategies.


2020 ◽  
Vol 12 (24) ◽  
pp. 2239-2275
Author(s):  
Siddappa A Patil ◽  
Amy P Hoagland ◽  
Shivaputra A Patil ◽  
Alejandro Bugarin

N-heterocyclic carbenes (NHCs) are organic compounds that typically mimic the chemical properties of phosphines. NHCs have made a significant impact on the field of coordination and organometallic chemistry because they are easy to prepare and handle and because of their versatility and stability. Importantly, the physicochemical properties of NHCs can be easily fine-tuned by simple variation of substituents on the nitrogen atoms. Over the past few years, various NHC–metal complexes have been extensively used as metal-based drug candidates and catalysts (homogeneous or heterogeneous) for various applications. To help assist future work with these compounds, this review provides a thorough review on the latest information involving some biomedical applications of NHC–metal complexes. Specifically, this article focuses on recent advances in the design, synthesis, characterization and biomedical applications (e.g., antimicrobial and anticancer activity) of various NHC–metal complexes (metal: silver, gold, palladium, rhodium, ruthenium, iridium and platinum) covering work published from 2015 to 2020. It is hoped that the promising discoveries to date will help accelerate studies on the encouraging potential of NHC–metal complexes as a class of effective therapeutic agents.


2018 ◽  
Vol 115 (9) ◽  
pp. E1963-E1972 ◽  
Author(s):  
Mariusz Matyszewski ◽  
Seamus R. Morrone ◽  
Jungsan Sohn

The AIM2-ASC inflammasome is a filamentous signaling platform essential for mounting host defense against cytoplasmic dsDNA arising not only from invading pathogens but also from damaged organelles. Currently, the design principles of its underlying signaling network remain poorly understood at the molecular level. We show here that longer dsDNA is more effective in inducing AIM2 assembly, its self-propagation, and downstream ASC polymerization. This observation is related to the increased probability of forming the base of AIM2 filaments, and indicates that the assembly discerns small dsDNA as noise at each signaling step. Filaments assembled by receptor AIM2, downstream ASC, and their joint complex all persist regardless of dsDNA, consequently generating sustained signal amplification and hysteresis. Furthermore, multiple positive feedback loops reinforce the assembly, as AIM2 and ASC filaments accelerate the assembly of nascent AIM2 with or without dsDNA. Together with a quantitative model of the assembly, our results indicate that an ultrasensitive digital circuit drives the assembly of the AIM2-ASC inflammasome.


2017 ◽  
Vol 9 (23) ◽  
pp. 3477-3484
Author(s):  
Joseph L. Cantone ◽  
Craig Polson ◽  
Cong Wei ◽  
Valerie Guss ◽  
Michael K. Ahlijanian ◽  
...  

Stable isotope labeling of proteins affords indicators at the molecular level, specifically biomarkers, which may providein vivodata on disease diagnosis, progression, and treatment.


2009 ◽  
Vol 36 (6) ◽  
pp. 488 ◽  
Author(s):  
Susan M. Carthew ◽  
Briony Horner ◽  
Katherine M. W. Jones

Linear forest clearings created by utility corridors have the potential to fragment landscapes, create edge effects and isolate populations of plants and animals. Here, we investigated the impact of utility corridors on small terrestrial fauna inhabiting Nangwarry Native Forest Reserve, south of Penola in south-eastern South Australia. Twelve sites straddling linear clearings of two widths (1.5 and 4.2 m) were surveyed over 2 years with 53 traps arranged as five transects at each site. This resulted in a total of 933 captures of 18 vertebrate species, including four amphibians, eight reptiles and six mammals. Propensity for capture near edges v. interiors, distances moved between recaptures and willingness to cross linear clearings varied among species, and was not related to taxa groups. For example, the small skink Bassiana duperreyi was extremely mobile and crossed tracks regularly. At the other extreme, the frog Neobatrachus pictus was more likely to be caught on interior transects and was never recorded moving between captures. The small dasyurid Antechinus flavipes was the most regularly caught species, and made both short- (<50 m) and long-distance (>1500 m) movements, with longer moves made by dispersing juveniles. Movements by this species often involved clearing crossings, although these were more likely when time between recaptures was longer, particularly for females. However, the overall rate of crossings for this species was not different from that expected if movements were random. In conclusion, the relatively narrow utility corridors studied here did not appear to affect the mobility of the majority of vertebrates significantly, with approximately half of the 85 movements recorded being of animals crossing a clearing, and no significant difference between the proportion crossing the wider (4.2 m) and the narrower (1.5 m) clearings. The present study is one of only a handful investigating movement patterns in reptiles and amphibians, particularly in relation to disturbances. However, sample sizes were small for some species, and future work should focus on those species that look to be either particularly mobile or sedentary, and encompass responses to the wider (up to 15 m) permanent tracks in the region.


2021 ◽  
Vol 11 ◽  
Author(s):  
Janet Y. Nale ◽  
Gurinder K. Vinner ◽  
Viviana C. Lopez ◽  
Anisha M. Thanki ◽  
Preeda Phothaworn ◽  
...  

Salmonella spp. is a leading cause of gastrointestinal enteritis in humans where it is largely contracted via contaminated poultry and pork. Phages can be used to control Salmonella infection in the animals, which could break the cycle of infection before the products are accessible for consumption. Here, the potential of 21 myoviruses and a siphovirus to eliminate Salmonella in vitro and in vivo was examined with the aim of developing a biocontrol strategy to curtail the infection in poultry and swine. Together, the phages targeted the twenty-three poultry and ten swine prevalent Salmonella serotype isolates tested. Although individual phages significantly reduced bacterial growth of representative isolates within 6 h post-infection, bacterial regrowth occurred 1 h later, indicating proliferation of resistant strains. To curtail bacteriophage resistance, a novel three-phage cocktail was developed in vitro, and further investigated in an optimized Galleria mellonella larva Salmonella infection model colonized with representative swine, chicken and laboratory strains. For all the strains examined, G. mellonella larvae given phages 2 h prior to bacterial exposure (prophylactic regimen) survived and Salmonella was undetectable 24 h post-phage treatment and throughout the experimental time (72 h). Administering phages with bacteria (co-infection), or 2 h post-bacterial exposure (remedial regimen) also improved survival (73–100% and 15–88%, respectively), but was less effective than prophylaxis application. These pre-livestock data support the future application of this cocktail for further development to effectively treat Salmonella infection in poultry and pigs. Future work will focus on cocktail formulation to ensure stability and incorporation into feeds and used to treat the infection in target animals.


Quaternary ◽  
2019 ◽  
Vol 2 (2) ◽  
pp. 15 ◽  
Author(s):  
Valentí Rull

The discovery and settlement of the tiny and remote Easter Island (Rapa Nui) has been a classical controversy for decades. Present-day aboriginal people and their culture are undoubtedly of Polynesian origin, but it has been debated whether Native Americans discovered the island before the Polynesian settlement. Until recently, the paradigm was that Easter Island was discovered and settled just once by Polynesians in their millennial-scale eastward migration across the Pacific. However, the evidence for cultivation and consumption of an American plant—the sweet potato (Ipomoea batatas)—on the island before the European contact (1722 CE), even prior to the Europe-America contact (1492 CE), revived controversy. This paper reviews the classical archaeological, ethnological and paleoecological literature on the subject and summarizes the information into four main hypotheses to explain the sweet potato enigma: the long-distance dispersal hypothesis, the back-and-forth hypothesis, the Heyerdahl hypothesis, and the newcomers hypothesis. These hypotheses are evaluated in light of the more recent evidence (last decade), including molecular DNA phylogeny and phylogeography of humans and associated plants and animals, physical anthropology (craniometry and dietary analysis), and new paleoecological findings. It is concluded that, with the available evidence, none of the former hypotheses may be rejected and, therefore, all possibilities remain open. For future work, it is recommended to use the multiple working hypotheses framework and the strong inference method of hypothesis testing, rather than the ruling theory approach, very common in Easter Island research.


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