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Tag: Japan

Novel “Hydrogel” Carriers for Anti-Cancer Drugs Offer New Hope for Cancer Treatment

Posted on by Tokyo University of Science

Hydrogels are often used as drug delivery systems, but to be effective carriers for anti-cancer drugs, they need to be responsive to varied stimuli in the tumour microenvironment. Now, scientists from Japan have developed novel hydrogels to effectively deliver drugs to tumour sites in response to temperature and pH changes in the tumour microenvironment.

These multi-stimuli-responsive hydrogels can eliminate remnant cancer cells following tumour excision through controlled drug release, offering hope for effective cancer treatment.

A team of scientists, led by Professor Akihiko Kikuchi from Tokyo University of Science, reports the production of unique degradable hydrogels that respond to changes under multiple conditions in “reducing” environments mimicking the microenvironment of tumors.

As Prof. Kikuchi observes, “In order to prepare degradable hydrogels that can release drugs in response to changes in the tumor microenvironment, we prepared hydrogels that respond to temperature, pH, and reducing environment, and analyzed their properties.”

In their study published in the Journal of Controlled Release, Prof. Kikuchi—along with his colleagues from Tokyo University of Science, Dr. Syuuhei Komatsu, Ms. Moeno Tago, and Ms. Yu Ando, and his collaborator on the study, Prof. Taka-Aki Asoh from Osaka University—details the steps of designing these novel hydrogels from the synthetic polymer poly(ethylene glycol) diglycidyl ether and the sulfur-containing organic compound cystamine. In response to low temperatures, these hydrogels swell up while they shrink at the physiological temperature.

Additionally, the hydrogels respond to pH changes by virtue of possessing tertiary amino groups. It must be noted here that the pH of the tumour microenvironment fluctuates between 5.5 and 6.5 owing to glycolysis in the tumour cells. Under the reducing conditions of this environment, the hydrogels degrade because of the breakage of disulfide bonds and change into low molecular-weight water-soluble oligomers that are easily excreted from the body.

To further test their drug release properties, the scientists loaded these hydrogels with specific proteins by exploiting their temperature-dependent swelling-deswelling behavior and tested the controlled release of drugs under acidic or reducing conditions.

It was found that the amount of drug loaded onto these hydrogels could be controlled by changing the mesh size of the hydrogel polymer network by changing temperature, suggesting the possibility of customizing these DDSs for specific drug delivery. Besides, the hydrogel network structure and electrostatic interactions in the network ensured that the proteins were preserved intact until delivery, unaffected by the swelling and shrinking of the hydrogels with pH changes in the surrounding environment.

The scientists found that the loaded protein drugs were completely released only under reducing conditions.

Using these hydrogels and the traceability that they provide, doctors may soon be able to design “customized” hydrogels that are specific to patients, giving personalized medicine a big boost. In addition to that, this new DDS provides a way to kill cancer cells that are left behind after surgery.

As Prof. Kikuchi states, “The implantation of this material in the affected area after cancer resection may eliminate residual cancer cells, making it a more powerful therapeutic tool”.

As cancer tightens its vice grip around the world, treatment options need to be varied and upgraded for customized and effective therapy. This unique and simple design technique to produce multi-stimuli-responsive hydrogels for effective drug delivery to target tumour sites may just be one among several such promising techniques to mount an answer to the challenge cancer poses to humanity.

Betting on drones as smart agricultural tools for pesticide use in farms

Posted on by Tokyo University of Science

Drones could soon be adopted as essential tools for various agricultural tasks; however, with respect to their use in farm management, research is still lacking. To address this issue, researchers in Japan compared drones to well-established technologies for spraying pesticide over rice paddy fields.

Using statistical data, the researchers explore both advantages and limitations of drones and whether they currently offer an edge regarding costs, capacity, and management efficiency.

“Following recent technological demonstrations and verifications at field sites, there is an increasing need for farm management research of smart agricultural technology including cost and efficiency analyses; this is essential for its implementation in farms,” explains Yuna Seo, who is Junior Associate Professor at Tokyo University of Science, Japan.

In an effort to address this knowledge gap, Seo led a recent study published in MDPI’s
Sustainability in which she, with her student Shotaro Umeda, compared different pesticide spraying technologies using realistic data.

More specifically, the researchers evaluated and compared the costs, working capacity, and management efficiency of drones versus remote-controlled (RC) helicopters and tractor-mounted boom sprayers for preventively spraying pesticides over rice paddies. They made these comparisons for seven different paddy field areas to take into account differences in scale for each method.

In terms of pest-control costs, the UAVs were only slightly less expensive per unit area than the boom sprayers, mainly due to the low price of drones and savings in fuel. In this regard, the RC helicopters were much more expensive.

“Although the purchase cost of boom sprayers is almost double that of UAVs, the fixed costs of both end up being similar because of the high operation, maintenance and repair costs of drones, which are notorious obstacles in UAV introduction and adoption,” remarks Seo.

As for the working capacity, RC helicopters could cover much more area per hour than both drones and boom sprayers. Still, drones had a slight advantage in daily area coverage over boom sprayers.

Finally, to explore the management efficiency of each method, the researchers used a technique called “data envelopment analysis,” which is widely used in economy and operations management to benchmark the performance of manufacturing and service operations.

The results indicated that both boom sprayers and UAVs reached
maximum or near-maximum efficiency for most paddy areas, while RC helicopters
were much less efficient.

Overall, this study showcased the benefits of drones as tools for rice production and compared them to other well-established technologies.   But, the use of drones in agriculture is not without limitations, which should be addressed in the future, such as the modification of aviation laws that forbid higher pesticide payloads on drones, as well as maintenance costs.

“The total costs and efficiency of UAVs would be comparable to that of boom sprayers, which is not a hindrance for farmers wanting to switch to drones. Therefore, technological advances and deregulation are necessary to expand the use of UAVs while meeting safety measures and ensuring applicability,” explains Seo.

In conclusion, this study highlights both the advantages and limitations of using drones as agricultural tools. Still, there is no doubt that smart agriculture as a whole could greatly alleviate the labour shortage problems in countries with a rapidly ageing population, of which Japan is a prime example.

A new algae-based switch is lighting up biological research

Posted on by NITech

A group of scientists from the Nagoya Institute of Technology, Japan, have discovered a novel ion channel protein that can be controlled by light, in a species of terrestrial alga. These channels respond to the shorter indigo blue wavelength of light, the first discovery of its kind. Subsequent light-based manipulations of the channel find potential applications in the modulations of specific functions of nerves, muscles, and more, for biological research.

Scientists from the Nagoya Institute of Technology, Japan, and Jawaharlal Nehru University, India, have identified a channelrhodopsin that responds to an even shorter indigo blue wavelength of light.

In their study published in Nature’s Communications Biology, the group of researchers,
led by Professor Hideki Kandori and Associate Professor Satoshi P. Tsunoda, identified a novel channelrhodopsin, which they named KnChR, from a species of terrestrial alga called Klebsormidium nitens.

“We chose this alga because it is known to be responsive to light, but its photoreceptor domain has not been established,” reports Prof. Kandori. Unlike other discovered channelrhodopsins, KnChR was found to respond to indigo blue light.

It is known that KnChR is made up of a seven-cell membrane-spanning region, which forms the pore that allows the entry and exit of different ions. This region is followed by a protein moiety including a peptidoglycan binding domain.

In order to investigate the properties of KnChR, the researchers performed extensive genetic and electrophysiological experiments.

What was perhaps the most exciting result was that they could identify the role of the “cytoplasmic domain.” All known channelrhodopsins have a large “cytoplasmic domain,” or the region that is located in the internal area of the cell. As Prof. Kandori explains, “All currently known channelrhodopsins comprise a large cytoplasmic domain, whose function is elusive. We found that the cytoplasmic domain of KnChR modulates the ion channel properties.”

Accordingly, the results of the experiments showed that changing the lengths of the cytoplasmic domain caused changes in ion channel closure. Particularly, the shortening of the domain resulted in increased channel ‘open time’ by more than ten-fold.

In addition, the researchers also identified two arginine amino acid residues, namely R287 and R291, in the same region, which played an important role in the properties of generated light currents. They found that KnChR exhibited maximal sensitivity at 430 nm and 460 nm, making it the ‘bluest’ channelrhodopsin.

Overall, the researchers have faith in the KnChR being helpful in biological systems requiring specific excitation parameters. When asked about the implications of these findings, Prof. Tsunoda, who is the corresponding author of the study suggests, “KnChR would expand the optogenetics tool kit, especially for dual light applications when short-wavelength excitation is required.”

What this means is that the light-operated property of KnChR can be applied in targeted manipulation of an organism’s biological functions, in a research setting. A few examples would include manipulation of neuronal and myocyte activities.

It is hoped that the scope of this discovery would expand beyond the laboratory into real-world applications. These real-world applications could include a cure for Alzheimer’s disease and heart diseases, light therapy for recovery from depression, and visual restoration.

Using a menthol-like compound to activate plant immune mechanisms

Posted on by Tokyo University of Science

Certain chemicals can activate the innate defence mechanisms of plants, and researchers at the Tokyo University of Science are working on ways to use such chemicals as alternatives to harmful agricultural pesticides.

These researchers have found that a compound derived from menthol can boost the expression of defence-related genes in soybeans, corn, peas, and other crop species. This finding may pave the way to green agricultural technologies that shield crops from pests while minimizing damage to the environment.

Professor Gen-ichiro Arimura of the Tokyo University of Science, Japan, notes that “the development of agricultural technology to date has been largely reliant on the use of pesticides and chemical fertilizers, which has resulted in
environmental pollution and the destruction of ecosystems.”

As a greener alternative to pesticides, terpenoid signalling molecules may help farmers continue their production of vital foodstuffs while lessening the associated environmental costs.

In pursuit of this goal, Prof. Arimura and his colleagues chose to investigate the terpenoid compound menthol, which is derived from mint leaves and can activate plant immune
systems. The aim of this project, which the researchers describe in an article recently published in the journal Plant Molecular Biology, was to develop compounds that are structurally similar to menthol but improve upon menthol’s ability to activate
plant immune systems.

The researchers therefore experimented with chemically modifying menthol by attaching amino acids, which are a structurally diverse set of compounds that living cells use to construct proteins. In total, the researchers synthesized six different menthol derivatives with attached amino acids.

The researchers then tested the resulting menthol derivatives to see whether the modified compounds could outperform unmodified menthol at activating plant defense mechanisms. To do this, they treated soybean leaves with either menthol or one of the six menthol derivatives to see which of the derivatives, if any, could outclass menthol itself at boosting the expression levels of two defense-related soybean genes after 24 hours of exposure. The found that only one of the modified compounds bested menthol, and this compound
is called valine menthyl ester, or “ment-Val” for short.

The researchers found that spraying soybean leaves once with a ment-Val solution boosted expression of the defence-related genes for three days, and second spraying on the fourth day worked to boost the expression of those genes again.

These findings suggest that ment-Val could provide sustainable pest control for farmers growing soybeans. Further experiments showed that ment-Val also increased the expression of defence-related genes in other crops, including peas, tobacco, lettuce, and corn. Ment-Val also proved to be quite stable under various conditions, which suggests that farmers would probably not lose the compound to degradation during storage.

Overall, these results suggest that ment-Val could be extremely useful as an alternative to the chemical pesticides that so many farmers rely on. Prof. Arimura notes that spraying ment-Val may be an effective way “to reduce pest damage to soybeans and other crops.”

He has applied for a patent on ment-Val’s use as a crop protection agent, and he predicts that the commercialization of ment-Val “will generate billions of yen in economic benefits through its usage by companies operating in the fields of horticulture and agriculture.”

He also notes that ment-Val’s anti-inflammatory properties could make it useful for human medicine.

Asymmetric synthesis of Aziridine with a new catalyst can help develop novel medicines

Posted on by NITech

Aziridine structures are an important component of several medicines and pharmaceutical drugs, due to which reactions yielding desirable aziridine structures with high purity have received much interest. In a new study, scientists from Japan have reported a high yield of aziridines with high purity from oxazolones using a novel catalyst and look into the underlying mechanism, paving the way for future development of novel drugs and medicines.

“Oxazolones are well-known for their versatility in affording biologically active compounds,” explains Professor Shuichi Nakamura from Nagoya Institute of Technology (NITech), Japan, who studies asymmetric reactions.

“However, the enantioselective reactions of 2H-azirines with oxazolones have not been very fruitful, despite being touted as one of the most efficient methods to synthesize aziridines.”

In a new study recently published in Organic Letters, Prof. Nakamura along with his colleagues from NITech and Osaka University, Japan, explored this issue and, in a significant breakthrough, managed to obtain aziridine-oxazolone compounds in high yields (99%) as well as high enantioselectivity or purity (98%). In addition, the team used an original catalyst they developed to catalyze the reactions they studied.

The team started off by heating α-azideacrylates at 150°C in an organic solvent tetrahydrofuran (THF) to prepare 2H-azirines and then reacted them with oxazolones in presence of various organocatalysts to produce different aziridine-oxazolone compounds.

In particular, the team examined the effect of the catalyst cinchonine and various heteroarenecarbonyl and heteroarenesulfonyl groups in organocatalysts derived from cinchona alkaloids and found that reactions using catalysts with either a 2-pyridinesulfonyl group or an 8-quinolinesulfonyl group gave both a high yield (81-99%) as well high enantiopurity (93-98%).

In addition, scientists observed that the reaction between a 2H-azirine containing an ethyl ester group and an oxazolone with a 3, 5-dimethoxyphenyl group in presence of the catalyst with 8-quinolinesulfonyl group also gave high yields (98-99%) as well as enantiopurity (97-98%).

The team then moved on to exploring the reaction between 2H-azirine with ethyl ester group and a wider variety of oxazolones in presence of the catalyst with 8-quinolinesulfonyl group.

In all of the reactions, they observed high yields (77-99%) and enantiopurities (94-99%) except one for the case of an oxazolone bearing a benzyl group and the catalyst with a 2-pyridylsulfonyl group that only produced a moderate yield (61%) and purity (86%). Moreover, they were able to convert the obtained aziridines into various other enantiomers without any loss of purity.

Finally, the team proposed a catalytic mechanism and a transition state for the reaction of 2H-azirines with oxazolones in which the catalyst activates both the oxazolone and the 2H-azirine, which then react to give an “addition product” that, in turn, yields the aziridine with the regeneration of the catalyst.

While the detailed mechanism is yet to be clarified, scientists are excited by their findings and look forward to the method’s application in medicine and pharmacology.

“It has the potential to provide people with new medicines and create new drugs as well as drug candidates that are currently difficult to synthesize. Moreover, the catalyst used in this study can be used for many other stereoselective synthetic reactions,” observes an
optimistic Prof. Nakamura.