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Comment by Dr. Krishna Kumari Challa on September 24, 2020 at 6:32am

Scientists devise 'Trojan horse' approach to kill cancer cells without using drugs

Cancer cells have been killed in lab experiments and tumor growth reduced in mice, using a new approach that turns a nanoparticle into a 'Trojan horse' that causes cancer cells to self-destruct, a research team has found.

The researchers created their 'Trojan horse' nanoparticle by coating it with a specific amino acid—L-phenylalanine—that cancer cells  rely on, along with other similar amino acids, to survive and grow. L-phenylalanine is known as an 'essential' amino acid as it cannot be made by the body and must be absorbed from food, typically from meat and dairy products.

Studies by other research teams have shown that cancer tumor growth can be slowed or prevented by 'starving' cancer cells of amino acids. Scientists believe that depriving cancer cells of amino acids, for example through fasting or through special diets lacking in protein, may be viable ways to treat cancer.

However, such strict dietary regimes would not be suitable for all patients, including those at risk of malnutrition or those with cachexia—a condition arising from chronic illness that causes extreme weight and muscle loss. Furthermore, compliance with the regimes would be very challenging for many patients.

So researchers devised a novel alternative approach. They took a silica nanoparticle designated as 'Generally Recognized As Safe' by the US Food and Drug Administration and coated it with L-phenylalanine, and found that in lab tests with mice it killed cancer cells effectively and very specifically, by causing them to self-destruct.

The anti-cancer therapeutic nanoparticle is ultrasmall, with a diameter of 30 nanometres, or approximately 30,000 times smaller than a strand of human hair, and is named "Nanoscopic phenylalanine Porous Amino Acid Mimic", or Nano-pPAAM.

The scientists tested the efficacy of Nano-pPAAM in the lab and in mice and found that the nanoparticle killed about 80 per cent of breast, skin, and gastric cancer cells, which is comparable to conventional chemotherapeutic drugs like Cisplatin. Tumor growth in mice with human triple negative breast cancer cells was also significantly reduced compared to control models.

Further investigations showed that the amino acid coating of Nano-pPAAM helped the nanoparticle to enter the cancer cells through the amino acid transporter cell LAT1. Once inside the cancer cells, Nano-pPAAM stimulates excessive reactive oxygen species (ROS) production—a type of reactive molecule in the body—causing cancer cells to self-destruct while remaining harmless to the healthy cells.

Zhuoran Wu et al, Potent‐By‐Design: Amino Acids Mimicking Porous Nanotherapeutics with Intrinsic Anticancer Targeting Properties, Small (2020). DOI: 10.1002/smll.202003757

https://phys.org/news/2020-09-scientists-trojan-horse-approach-canc...

Comment by Dr. Krishna Kumari Challa on September 24, 2020 at 5:55am

Customizable synthetic antibiotic outmaneuvers resistant bacteria

Antibiotic resistance is one of the world's most urgent public health threats.

Researchers now are tackling antibiotic resistance using a different approach: redesigning existing antibiotic molecules to evade a bacterium's resistance mechanisms. By devising a set of molecular LEGO pieces that can be altered and joined together to form larger molecules, the researchers have created what they hope is the first of many "rebuilds" of drugs that had been shelved due to antibiotic resistance. The aim is to revive classes of drugs that haven't been able to achieve their full potential, especially those already shown to be safe in humans. If we can do that, it eliminates the need to continually come up with new classes of drugs that can outdo resistant bacteria. Redesigning existing drugs could be a vital tool in this effort.

Synthetic group A streptogramin antibiotics that overcome Vat resistance, Nature (2020). DOI: 10.1038/s41586-020-2761-3 , www.nature.com/articles/s41586-020-2761-3

https://phys.org/news/2020-09-customizable-synthetic-antibiotic-out...

Comment by Dr. Krishna Kumari Challa on September 24, 2020 at 5:43am

3-D bioprinting constructs for cartilage regeneration

Cartilage injury is a common cause of joint dysfunction and existing joint prostheses cannot remodel with host joint tissue. However, it is challenging to develop large-scale biomimetic anisotropic constructs that structurally mimic native cartilage.

 In  new reports, scientists detailed anisotropic cartilage regeneration using three-dimensional (3-D) bioprinting dual-factor releasing gradient-structured constructs. The team used the dual-growth-factor releasing mesenchymal stem cell (MSC)-laden hydrogels for chondrogenic differentiation (cartilage development). The 3-D bioprinted cartilage constructs showed whole-layer integrity, lubrication of superficial layers and nutrient supply into deeper layers. The scientists tested the cartilage tissue in the lab and in animal models to show tissue maturation and organization for translation to humans after sufficient experimental studies. The one-step, 3-D printed dual-factor releasing gradient-structured cartilage constructs can assist regeneration of MSC- and 3-D bioprinted therapy for injured or degenerative joints.

Ye Sun et al. 3D bioprinting dual-factor releasing and gradient-structured constructs ready to implant for anisotropic cartilage regeneration, Science Advances (2020). DOI: 10.1126/sciadv.aay1422

Chang H Lee et al. Regeneration of the articular surface of the rabbit synovial joint by cell homing: a proof of concept study, The Lancet (2010). DOI: 10.1016/S0140-6736(10)60668-X

April M Craft et al. Generation of articular chondrocytes from human pluripotent stem cells, Nature Biotechnology (2015). DOI: 10.1038/nbt.3210

Benjamin R. Freedman et al. Biomaterials to Mimic and Heal Connective Tissues, Advanced Materials (2019). DOI: 10.1002/adma.201806695

https://medicalxpress.com/news/2020-09-d-bioprinting-cartilage-rege...

Comment by Dr. Krishna Kumari Challa on September 23, 2020 at 10:10am

How The Brain Prepares For The Eyes To See Computer simulations show that spontaneous activity in the developing retina could help the visual cortex form properly prior to input from the eyes. Read more from Asian Scientist Magazine at: https://www.asianscientist.com/2020/09/in-the-lab/visual-cortex-spo...

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3-D Printing inside the Body Could Patch Stomach Ulcers

In vivo bioprinting might also help repair hernias and treat infertility

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The Quantum Butterfly Noneffect

A familiar concept from chaos theory turns out to work differently in the quantum world

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** New analysis of black hole reveals a wobbling shadow

https://phys.org/news/2020-09-analysis-black-hole-reveals-shadow.ht...

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Researchers pinpoint how iron deposits form

The findings shed new light on how iron deposits form—and this new understanding can aid geologists in the hunt for more ore.

https://phys.org/news/2020-09-iron-deposits.html?utm_source=nwlette...

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Bushfires release decades of pollutants absorbed by forests

We know forests absorb carbon dioxide, but, like a sponge, they also soak up years of pollutants from human activity. When bushfires strike, these pollutants are re-released into the air with smoke and ash.

Comment by Dr. Krishna Kumari Challa on September 23, 2020 at 8:59am

SCI-COM: Scientists don’t share their findings for fun – they want their research to make a difference

Scientists don’t take time away from their research to share their expertise with journalists, policymakers and everyone else just to let us know about neat scientific facts. They share findings from their research because they want leaders and the public to use their hard-won insights to make evidence-based decisions about policy and personal issues. That’s according to two surveys of  researchers  conducted.

Scientists  reported “ensuring that policymakers use scientific evidence” is at the top of their list of communication goals. Helping their fellow citizens make better personal decisions also scores high. Further, scientists say they’re not communicating just to burnish their own reputation.

We know from other interviews and surveys that many scientists will often initially indicate that their communication “goal” is simply to increase knowledge or correct misinformation. However, if prodded by questions like “But why do you want to increase knowledge?” or “What do you hope will happen if you correct misinformation?” they will often identify their ultimate aim as helping people make better decisions.

Highly trained scientists seem especially willing to share what they’ve learned if they think it can help society make smarter choices. 

Scientists are more likely to say they’re willing to communicate, as well as to prioritize specific objectives or tactics, if they see a choice as ethical, able to make a difference and within their capacity.

https://theconversation.com/scientists-dont-share-their-findings-fo...

Comment by Dr. Krishna Kumari Challa on September 23, 2020 at 8:41am

An acoustically actuated microscopic device

Researchers  have developed remote-controlled, mechanical microdevices that, when inserted into human tissue, can manipulate the fluid that surrounds them, collect cells or release drugs. This breakthrough offers numerous potential applications in the biomedical field, from diagnostics to therapy.

Murat Kaynak, Pietro Dirix, and Mahmut Selman Sakar. “Addressable Acoustic Actuation of 3D Printed Soft Robotic Microsystems,” Advanced Science, 2020.

https://onlinelibrary.wiley.com/doi/10.1002/advs.202001120 

https://actu.epfl.ch/news/an-acoustically-actuated-microscopic-devi...

https://researchnews.cc/news/2649/An-acoustically-actuated-microsco...

Comment by Dr. Krishna Kumari Challa on September 23, 2020 at 8:28am

Without oxygen, Earth's early microbes relied on arsenic to sustain life

Much of life on planet Earth today relies on oxygen to exist, but before oxygen was present on our blue planet, lifeforms likely used arsenic instead. These findings are detailed in research published recently.

A key component of the oxygen cycle is where plants and some types of bacteria essentially take sunlight, water, and CO₂, and convert them to carbohydrates and oxygen, which are then cycled and used by other organisms that breathe oxygen. This oxygen serves as a vehicle for electrons, gaining and donating electrons as it powers through the metabolic processes. However, for half of the time life has existed on Earth, there was no oxygen present, and for the first 1.5 billion years.

Light-driven, photosynthetic organisms appear in the fossil record as layered carbonate rocks called stromatolites dating to around 3.7 billion years ago, says Visscher. Stromatolite mats are deposited over the eons by microbial ecosystems, with each layer holding clues about life at that time. There are contemporary examples of microbes that photosynthesize in the absence of oxygen using a variety of elements to complete the process, however it's unclear how this happened in the earliest life forms.

Theories as to how life's processes functioned in the absence of oxygen have mostly relied on hydrogen, sulfur, or iron as the elements that ferried electrons around to fulfill the metabolic needs of organisms. These theories were contested though.

Arsenic is another theoretical possibility, and evidence for that was found in 2008.The link with arsenic was strengthened in 2014 when researchers found evidence of arsenic-based photosynthesis in deep time.

 found a blood red river. The red sediments are made up by anoxogenic photosynthetic bacteria. The water is very high in arsenic as well. The water that flows over the mats contains hydrogen sulfide that is volcanic in origin and it flows very rapidly over these mats. There is absolutely no oxygen."

The team also showed that the mats were making carbonate deposits and creating a new generation of stromatolites. The carbonate materials also showed evidence for arsenic cycling—that arsenic is serving as a vehicle for electrons—proving that the microbes are actively metabolizing arsenic, much like oxygen in modern systems. Visscher says these findings, along with the fossil evidence, gives a strong sense of the early conditions of Earth.

Pieter T. Visscher et al. Modern arsenotrophic microbial mats provide an analog for life in the anoxic Archean, Communications Earth & Environment (2020). DOI: 10.1038/s43247-020-00025-2

https://phys.org/news/2020-09-oxygen-earth-early-microbes-arsenic.h...

Comment by Dr. Krishna Kumari Challa on September 23, 2020 at 8:07am

New finding: Why some cancers may respond poorly to key drugs 

Patients with BRCA1/2 mutations are at higher risk for breast, ovarian and prostate cancers that can be aggressive when they develop—and, in many cases, resistant to lifesaving drugs. Now scientists  have identified a driver of the drug resistance that can make a life or death difference for patients with these cancers.

A major issue with cancer treatments is the development of resistance. When treatments stop working for patients, it's incredibly demoralizing and it's been a huge drive in research to understand these resistance mechanisms.

In a new paper published, researchers describe a protein that may help doctors predict which patients will become resistant to a class of drugs frequently used to treat BRCA 1/2-deficient tumours. The finding could help create more effective treatment plans for their patients.

The scientists identified that a protein called PCAF promotes DNA damage in BRCA 1/2-mutated cancer cells. Patients with low levels of this protein are likely to have poor outcomes and develop resistance to a type of drug that is used to treat BRCA-deficient tumors, called a PARP inhibitor.

PARP inhibitors are an important breakthrough in treating these aggressive cancers. What the researchers  found now 's that when levels of PCAF are low, it actually protects the cancer cells from this drug. By testing biopsy samples, doctors may be able to tell using PCAF as a molecular marker for PARP inhibitor responses what treatment may work best for a patient."

Fortunately, there is already another class of drugs on the market, called HDAC inhibitors, that can boost the effectiveness of the PCAF protein. HDAC inhibitors and PARP inhibitors have the potential to be prescribed as a combination therapy.

Molecular Cell (2020). DOI: 10.1016/j.molcel.2020.08.018

https://medicalxpress.com/news/2020-09-cancers-poorly-key-drugs.htm...

Comment by Dr. Krishna Kumari Challa on September 23, 2020 at 6:29am

New drug candidate found for hand, foot and mouth disease

A study  offers some good news in the search for antiviral drugs for hard-to-treat diseases. Researchers have identified a potential new drug candidate against enterovirus 71, a common cause of hand, foot and mouth disease in infants and young children. While most people get better within 7 to 10 days after suffering little more than a fever and rash, severe cases can cause brain inflammation, paralysis and even death.

The compound of interest is a small molecule that binds to RNA, the virus's genetic material, and changes its 3-D shape in a way that stops the virus from multiplying without harming its human host.

"Small Molecule Targeting IRES Domain Inhibits Enterovirus 71 Replication via an Allosteric Mechanism that Stabilizes a Ternary Complex," Nature Communications (2020). DOI: 10.1038/s41467-020-18594-3

https://medicalxpress.com/news/2020-09-drug-candidate-foot-mouth-di...

Comment by Dr. Krishna Kumari Challa on September 23, 2020 at 6:24am

Scientists identify hormone that might help treat malabsorption

Scientists  used human intestinal organoids grown from stem cells to discover how our bodies control the absorption of nutrients from the food we eat. They further found that one hormone might be able to reverse a congenital disorder in babies who cannot adequately absorb nutrients and need intravenous feeding to survive.

Researchers found that the hormone peptide YY, also called PYY, can reverse congenital malabsorption in mice. With a single PYY injection per day, 80% of the mice survived. Normally, only 20% to 30% survive. This indicates PYY might be a possible therapeutic for people with severe malabsorption.

Poor absorption of macronutrients is a global health concern, underlying ailments such as malnutrition, intestinal infections and short-gut syndrome. So, identification of factors regulating nutrient absorption has significant therapeutic potential. Scientists reported that the absorption of nutrients—in particular, carbohydrates and proteins—is controlled by enteroendocrine cells  in the gastrointestinal tract.

Babies born without enteroendocrine cells —or whose enteroendocrine cells don't function properly—have severe malabsorption and require IV nutrition. This work could help them.

Enteroendocrine cells couple nutrient sensing to nutrient absorption by regulating ion transport," Nature Communications (2020). DOI: 10.1038/s41467-020-18536-z

https://medicalxpress.com/news/2020-09-scientists-hormone-malabsorp...

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