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Comment by Dr. Krishna Kumari Challa 10 hours ago

Centipedes used in traditional Chinese medicine offer leads for kidney treatment

A venomous, 8-inch centipede may be the stuff of nightmares, but it could save the life of those affected by kidney disease. Researchers report in the Journal of Natural Products that the many-legged critter—used in traditional Chinese medicine—contains alkaloids that in cell cultures reduced inflammation and renal fibrosis, which both contribute to kidney disease.

Some 1,500 species of animals are used in traditional Chinese medicine, but little is known about many of the secondary metabolites their bodies produce for specialized functions such as immobilizing prey. The few compounds that have been studied, such as toad venom for cancer treatment, have proved to be fruitful leads for drug development.

The researchers 

decided to examine the secondary metabolites produced by the Chinese red-headed centipede (Scolopendra subspinipes mutilans). The venomous centipede has been used for thousands of years in treatments for conditions including epilepsy, tuberculosis, burns and cardiovascular disease.

The researchers mixed a sample of dried centipede powder with ethanol to extract numerous compounds from the animals and then separated and identified the constituents with techniques such as chromatography and spectrometry. The team found 12 new quinoline and isoquinoline alkaloids, including some with unusual molecular structures, along with a half dozen other alkaloids that had previously been detected in this species or in plants.

In cell cultures, some of the alkaloids showed anti-inflammatory behavior, while a portion also reduced renal fibrosis. This buildup of connective tissue is associated with chronic kidney disease and is stimulated by inflammation. Finally, the researchers identified a protein that plays a role in renal fibrosis and that was targeted by the most effective dual-function alkaloid. This information could provide a lead for developing treatments for kidney disease, according to the researchers.

Bin-Yuan Hu et al, Structurally Diverse Alkaloids with Anti-Renal-Fibrosis Activity from the Centipede Scolopendra subspinipes mutilans, Journal of Natural Products (2024). DOI: 10.1021/acs.jnatprod.4c00044

Comment by Dr. Krishna Kumari Challa 11 hours ago

The team tested its E. coli-based delivery system in mouse models of pancreatic ductal adenocarcinoma, or PDAC, the most common and lethal form of pancreatic cancer, which was the focus of the study.

Mice treated with the therapeutic-laden bacteria experienced delayed tumour growth and significantly longer survival compared with mice that received other treatments. Postmortem analyses also showed that tumors treated with the nano-drug-carrying E. coli had the greatest infiltration of cancer-fighting immune cells among all treatments.

Zhaoting Li et al, Nanodrug-bacteria conjugates-mediated oncogenic collagen depletion enhances immune checkpoint blockade therapy against pancreatic cancer, Med (2024). DOI: 10.1016/j.medj.2024.02.012

Part2

Comment by Dr. Krishna Kumari Challa 11 hours ago

Nano-drugs hitching a ride on bacteria could help treat pancreatic cancer

Many pancreatic tumors are like malignant fortresses, surrounded by a dense matrix of collagen and other tissue that shields them from immune cells and immunotherapies that have been effective in treating other cancers. Employing bacteria to infiltrate that cancerous fortification and deliver these drugs could aid treatment for pancreatic cancer, according to newly published findings from a team of researchers.

The paper is published in the journal Med.

Tumor collagen is a tough barrier

Pancreatic cancer is well known for its deadliness and has among the lowest five-year survival rates among common cancers. While there are several drivers behind the disease's dismal prognosis, one that's the focus of this study is the matrix surrounding many pancreatic tumors, which acts as an effective barrier against treatment.

The barrier is a collection of collagen, connective tissue, proteins that facilitate fibrosis and other cells. Recent studies have highlighted the role of this barrier in counteracting treatment attempts with immunotherapies—treatments that work by spurring on or tamping down the patient's immune system—such as immune checkpoint inhibitors. Analyzing patient tumour samples, the research team found genetic evidence that a specific type of collagen, called oncogenic collagen, is indeed a barrier to immunotherapy-based treatments.

That really dense extracellular matrix, made up of immunosuppressive cells, collagens and other cells is a critical problem if we want to use immunotherapies against these pancreatic cancers.

So researcher s  applied a bacterium that could both penetrate through the tough collagen barrier and deliver immunotherapeutic "nano-drugs."

The team chose a strain of the bacterium Escherichia coli with a track record of safe use in humans and known affinity for low-oxygen environments such as tumors to serve as a drug delivery vehicle. They engineered "protein cages" containing a pair of drugs—one breaks down collagen and the other is an anticancer immune checkpoint inhibitor—and attached them to the E. coli.

E. coli has great motility, meaning it can move by itself, and it actively targets hypoxic environments like tumors. And the researchers found that it was able to penetrate deep into the tumor site to deliver drugs.

Part1

Comment by Dr. Krishna Kumari Challa 11 hours ago

The study  took place at the Suaq Balimbing research site in Indonesia, which is a protected rainforest area home to approximately 150 critically endangered Sumatran orangutans.

During daily observations of the orangutans, the biologists noticed that a male named Rakus had sustained a facial wound, most likely during a fight with a neighbouring male.

Three days after the injury, Rakus selectively ripped off leaves of a liana with the common name Akar Kuning (Fibraurea tinctoria), chewed on them, and then repeatedly applied the resulting juice precisely onto the facial wound for several minutes. As a last step, he fully covered the wound with the chewed leaves.

This and related liana species that can be found in tropical forests of Southeast Asia are known for their analgesic and antipyretic effects and are used in traditional medicine to treat various diseases, such as malaria. Analyses of plant chemical compounds show the presence of furanoditerpenoids and protoberberine alkaloids, which are known to have antibacterial, anti-inflammatory, anti-fungal, antioxidant, and other biological activities of relevance to wound healing.

Observations over the following days did not show any signs of the wound becoming infected and after five days the wound was already closed.

Interestingly, Rakus also rested more than usual when being wounded. Sleep positively affects wound healing as growth hormone release, protein synthesis and cell division are increased during sleep. 

Like all self-medication behavior in non-human animals, the case reported in this study raises questions about how intentional these behaviors are and how they emerge.

The behavior of Rakus appeared to be intentional as he selectively treated his facial wound on his right flange, and no other body parts, with the plant juice. The behavior was also repeated several times, not only with the plant juice but also later with more solid plant material until the wound was fully covered. The entire process took a considerable amount of time.

It is possible, that wound treatment with Fibraurea tinctoria by the orangutans at Suaq emerges through individual innovation.

Orangutans at the site rarely eat the plant. However, individuals may accidentally touch their wounds while feeding on this plant and thus unintentionally apply the plant's juice to their wounds. As Fibraurea tinctoria has potent analgesic effects, individuals may feel an immediate pain release, causing them to repeat the behaviour several times.

Since the behaviour has not been observed before, it may be that wound treatment with Fibraurea tinctoria has so far been absent in the behavioural repertoire of the Suaq orangutan population. Like all adult males in the area, Rakus was not born in Suaq, and his origin is unknown.

This possibly innovative behavior presents the first report of active wound management with a biological active substance in a great ape species and provides new insights into the existence of self-medication in our closest relatives and in the evolutionary origins of wound medication more broadly.

Isabelle Laumer, Active self-treatment of a facial wound with a biologically active plant by a male Sumatran orangutan, Scientific Reports (2024). DOI: 10.1038/s41598-024-58988-7. www.nature.com/articles/s41598-024-58988-7

Part 2

Comment by Dr. Krishna Kumari Challa 11 hours ago

First report of wound treatment by a wild animal using a pain-relieving plant

Even though there is evidence of certain self-medication behaviours in animals, so far it has never been known that animals treat their wounds with healing plants.

Now biologists have observed this in a male Sumatran orangutan who sustained a facial wound. He ate and repeatedly applied sap from a climbing plant with anti-inflammatory and pain-relieving properties commonly used in traditional medicine. He also covered the entire wound with the green plant mesh. Thus, medical wound treatment may have arisen in a common ancestor shared by humans and orangutans.

While sick and avoidance behavior can be regularly observed in non-human animals, self-medication in the form of ingestion of specific plant parts is widespread in animals but exhibited at low frequencies. The closest relatives to humans, the great apes, are known to ingest specific plants to treat parasite infection and to rub plant material on their skin to treat sore muscles.

Recently a chimpanzee group in Gabon was observed applying insects to wounds. However, the efficiency of this behavior is still unknown. Wound treatment with a biologically active substance has so far not been documented.

In a study published in Scientific Reports, cognitive and evolutionary biologists from  report evidence of active wound treatment with a healing plant in a wild male Sumatran orangutan.

Part 1

Comment by Dr. Krishna Kumari Challa 11 hours ago

The brain structure that produces norepinephrine also helps control visual attention

The locus coeruleus (LC) is a small region of the brainstem that produces norepinephrine, a chemical with powerful effects on arousal and wakefulness which plays an important role in the body's response to stress or panic. Now, research shows it plays a specific role in visual sensory processing as well.

In a study, titled "Locus coeruleus norepinephrine selectively controls visual attention" and published in Neuron, neuroscientists artificially increased neuronal activity in the LC by briefly shining light on genetically modified neurons. They saw that this manipulation selectively enhanced performance in non-human primates performing a visual attention task, underscoring the crucial role that attention plays in sensory perception.

Researchers now have found a brain structure that has strong signals related to whether the subjects are paying attention to a stimulus or not, and they see big differences in how its neurons respond depending on where that attention is directed.

Previous research has shown that LC activation, coupled with its ensuing norepinephrine production, might improve performance on tasks that require attention to discern between visual stimuli.

Distinguishing the effects of attention from other factors, like decision-making or motor movements, is crucial. 

 Those processes take place in other parts of the brain, and can contribute to performance independently. Understanding how a relatively small brain structure like the LC impacts such an important function as attention is also one step toward solving the overall puzzle of the brain.

Locus coeruleus norepinephrine contributes to visual spatial attention by selectively enhancing perceptual sensitivity, Neuron (2024). DOI: 10.1016/j.neuron.2024.04.001. www.cell.com/neuron/fulltext/S0896-6273(24)00239-3

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Comment by Dr. Krishna Kumari Challa 12 hours ago

Testing for residual cancer cells before blood cell transplant therapy is important and practical, new study finds

Patients in remission after battling a high-risk blood cancer are likely to have better outcomes if no trace of the cancer is detectable before the patients receive donor blood cells.

The finding appearing in JAMA Oncology emphasizes the importance and practicality of testing for measurable residual disease (MRD)—a condition that refers to evidence of lingering cancer cells in the body after people receive apparently successful chemotherapy treatment in adults with acute myeloid leukemia.

The good news is this testing is doable.  You don't need to be at a specialized center with customized technology and high levels of expertise—testing can be done using commercially available kits potentially at any major modern hospital lab. It is now a matter of implementation.

In a study of 537 patients with AML treated throughout the United States, scientists used a method called targeted ultra-deep DNA sequencing to see if they could find specific, leftover cancer-related gene mutations in the blood of patients who were in remission, but still awaiting a bone marrow transplant from donors to restore their healthy blood supply.
The scientists were looking at DNA in blood for mutations in the FLT3 gene, which is among the most common seen in patients with AML. They found that if as little as 1 in 10,000 molecules of DNA tested contained a mutation, it corresponded with a higher risk of the cancer returning, and lower chances of survival with current standard treatments.

Measurable Residual FLT3-ITD before Allogeneic Transplant for Acute Myeloid Leukemia, JAMA Oncology (2024). DOI: 10.1001/jamaoncol.2024.0985

Comment by Dr. Krishna Kumari Challa 12 hours ago

The authors propose that the weakened magnetic field may have allowed more hydrogen to escape to space, resulting in a greater percentage of oxygen in Earth's atmosphere and oceans, which may in turn have supported the diversification in the types and complexity of organisms.

John Tarduno, Near-collapse of the geomagnetic field may have contributed to atmospheric oxygenation and animal radiation in the Ediacaran Period, Communications Earth & Environment (2024). DOI: 10.1038/s43247-024-01360-4. www.nature.com/articles/s43247-024-01360-4

Part 2

Comment by Dr. Krishna Kumari Challa 12 hours ago

Weak magnetic field may have supported diversification of life on Earth

An unusual reduction in the strength of Earth's magnetic field between 591 and 565 million years ago coincided with a significant increase in the oxygen levels in the atmosphere and oceans, according to a paper published in Communications Earth & Environment. The authors propose that the weakening of the magnetic field may have led to the increase in oxygen, which is  thought to have supported the evolution of some of the earliest complex organisms.

Between 600 and 540 million years ago, life on Earth consisted of soft-bodied organisms known as the Ediacaran fauna, the earliest known complex multicellular animals. The fossil record shows that these organisms significantly diversified in complexity and type between 575 and 565 million years ago. Previous research has suggested that this diversification is linked to a significant increase in atmospheric and oceanic oxygen levels that occurred over the same period. However, it is not yet clear why this increase in oxygen occurred.

Researchers analyzed the magnetic properties of 21 plagioclase crystals, a common mineral in Earth's crust, which were extracted from a 591-million-year-old rock formation in Brazil. Plagioclase crystals contain tiny magnetic minerals that preserve the intensity of the Earth's magnetic field at the time they are formed.
Analysis of the crystals showed that at their point of formation, Earth's magnetic field was the weakest ever recorded—some 30 times weaker than both the current magnetic field intensity, and that measured from similar crystals formed approximately 2,000 million years ago.
The authors combined their results with previous measurements to establish that the Earth's magnetic field was at this weak level for at least 26 million years, from 591 to 565 million years ago. This overlaps with the rise in oxygen, which occurred between 575 and 565 million years ago.

Part 1

Comment by Dr. Krishna Kumari Challa 12 hours ago

Male chicks play more than females!

Play is widespread, but far from ubiquitous, across the animal kingdom. Especially common in mammals, play is also known to occur in taxa as diverse as birds, fish, octopuses, and even insects. But what is its function, given that natural selection never selects fun for its own sake? One prominent hypothesis is that play is beneficial to individuals because it allows them to practice skills needed later in life.

Now, a study in Frontiers in Ethology has shown that male baby chickens play far more than females. This result is of interest given that domestic chickens are directly descended from a species—red jungle fowl—with a pronounced difference between the sexes in morphology, coloration, and behaviour.

This difference is mainly because males engage more in social and object play.

The researchers distinguished 12 distinct play behaviors. Examples of locomotor play were frolicking and wing flapping. Object play included chasing an object or pecking at it or exchanging it with another chick. Social play included sparring, jumping, and sparring stand-offs.

Object play was more frequently seen than social play, while locomotor play was least common. Both females and males showed every type of playful behavior. However, the frequency of play differed between them: male chicks played more overall than females. This was due to males engaging more often in object and social play, while there was no difference between the sexes in the frequency of locomotor play.

The researcher concluded that these sex differences in chicks in the frequency of play can be explained by the high degree of sexual dimorphism of adult junglefowl. This means that male chicks would benefit more from practicing various skills related to physical ability and social tactics.

The present study indicates that a possible function is to prepare animals for specific challenges they may encounter later in life. In a species like the chicken, where only males compete for territories, it makes sense that they engage in more social play as young.

Rebecca Oscarsson et al, Male chicks play more than females—sex differences in chicken play ontogeny, Frontiers in Ethology (2024). DOI: 10.3389/fetho.2024.1392378. www.frontiersin.org/articles/1 … ho.2024.1392378/full

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