Publisher Health

As far back as ancient Rome, spider silk has been used as a remedy to treat everything from skin lesions to warts. In the past, doctors have covered open wounds in cobwebs or advised patients to place cocoons on infected teeth. In modern times, however, the literature contains conflicting reports of whether or not spider silk has antimicrobial properties. In the journal iScience on October 5th, researchers revisit these old experiments and debunk the myth of antibiotic spider silk.
“Spider silk has always been admired and almost has a mythical status,” says senior author Trine Bilde, a professor of biology at Aarhus University. “It’s one of these myths that seems to have become ‘established’ by ‘belief’ and not by strong empirical support.”
Since the antimicrobial properties of spider silk were first reported, researchers have proposed ways in which spiders might benefit. In the case of social spiders living in large groups, it’s been thought that antibiotic silk might help prevent the spread of infection between individuals. These spiders have weakened immune systems from inbreeding, so they are especially vulnerable to infection.
Early in their research, Bilde and her research group grew doubtful of the validity of what they had read in the literature. “We were unable to detect antimicrobial activity of social spider silk, regardless of method or microbe, and this made us curious about why other studies were able to,” she says. “We then started scrutinizing the papers reporting antimicrobial activity in fine detail and became aware of methodological shortcomings.”
The researchers identified two categories of shortcomings in the already published literature: (1) risk for bacterial contamination, and (2) inadequate control for the solvent used to extract the spider silk. The team showed that previous reports were likely compromised, for example by having measured the effect of the solvent used to extract the spider silk instead of the spider silk itself. Solvents like acetone or ethyl acetate can have strong antimicrobial effects on their own.
Overall, Bilde’s team examined silk from seven different spider species by using improved experimental methods and found no signs of antimicrobial activity. Although this does not rule out antimicrobial activity for all species of spiders, it brings into doubt all previous reported accounts.
“Rather than assuming that spider silk is antimicrobial, we should now assume that it isn’t,” says Bilde. “We can still test the idea in new species and with new organisms, but with a more cautious starting point.”
Spiders use their silk to protect their eggs, which offer high nutritional content to microbes. Bilde proposes that instead of warding off microbial threats with intrinsic antimicrobial activity, the silk casing around the eggs might function only as a physical barrier.
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Materials provided by Cell Press. Note: Content may be edited for style and length.

In a recent study published in Cancer Research, a team led by researchers at Tokyo Medical and Dental University (TMDU) identified a specific small RNA molecule, called a microRNA (miRNA or miR), that has the potential to be used as an anti-cancer therapeutic. The new research indicates that the molecule, called miR-766-5p, can significantly reduce levels of the oncogene MYC — a specific gene that is expressed at high levels in tumor cells and helps fuel cancer growth and progression.
At its most basic level, cancer is driven by abnormal and uncontrolled gene expression. Numerous different molecular mechanisms contribute to the activation and overexpression of oncogenes in cancer. MiRNAs work as negative regulators of gene expression. This means that they can directly bind and interact with certain gene messages and block them from being translated into a protein. Therefore, any molecular pathway controlled by that specific protein is also affected by this miRNA-mediated regulation. In a previous study, the TMDU group used cell culture experiments to demonstrate that treating cancer cells with miR-766-5p resulted in lower MYC expression and inhibited cancer cell growth rates. Following these intriguing findings, the group aimed to determine the specific mechanism behind these results.
“MYC is a critical oncogene in many tumor types,” says lead author of the study Yasuyuki Gen. “It can promote cancer cell proliferation, can suppress the body’s immune response to fighting the cancer, and can generally be the main driver of tumor progression in many patients.”
The researchers found that miR-766-5p could directly target and reduce expression of two proteins called CBP and BRD4. CBP can induce a molecular change called acetylation that causes DNA to become more “open,” which allows genes present in that area to be more easily expressed. BRD4 can then be recruited to these sites and help promote transcription of these gene messages.
“Areas of DNA with high activity of proteins like CBP and BRD4 are known as super-enhancers,” explains Johji Inazawa, senior author. “Many cancer cells develop super-enhancers near oncogenes, like MYC, that drive increased oncogene expression and therefore promote cancer.”
The team then experimentally treated cells with a synthetic version of miR-766-5p, finding that the resulting suppression of CBP and BRD4 caused decreased MYC levels in cancer cells, but not in normal cells. Additionally, tumors that were engrafted in lab mice showed significantly suppressed growth when treated with miR-766-5p compared with a control miRNA.
“Our findings suggest that miR-766-5p-mediated control of CBP and BRD4 blocks formation of the super-enhancers that contribute to MYC overexpression in cancer cells,” explains Gen.
In recent years, efforts have been made to develop specific miRNAs into targeted therapies for various cancers. This study provides considerable evidence that miR-766-5p could be used to fight MYC-driven cancers by targeting super-enhancers.
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Materials provided by Tokyo Medical and Dental University. Note: Content may be edited for style and length.

A drug commonly used to treat cancer can restore memory and cognitive function in mice that display symptoms of Alzheimer’s disease, new UBC research has found.
The drug, Axitinib, inhibits the growth of new blood vessels in the brain — a feature shared by both cancer tumours and Alzheimer’s disease, but this hallmark represents a new target for Alzheimer’s therapies.
Mice with Alzheimer’s disease that underwent the therapy not only exhibited a reduction in blood vessels and other Alzheimer’s markers in their brains, they also performed remarkably well in tests designed to measure learning and memory.
“We are really very excited, because these findings suggest we can repurpose approved anti-cancer drugs for use as treatments for Alzheimer’s disease,” said Professor Wilf Jefferies, the study’s senior author and principal investigator at the Centre for Blood Research, Vancouver Prostate Centre and Michael Smith Laboratories. “It could shorten the clinical development by years.”
Alzheimer’s disease is estimated to affect 50 million people worldwide. The condition is characterized by cognitive decline, memory loss and dysfunctional changes in the brain.
Potential Alzheimer’s treatments have shown promise in animal models before, but failed in clinical trials. Typically, these strategies target a protein called tau or a protein fragment known as beta-amyloid, but the UBC researchers chose a different approach. They left the traditional targets alone and instead focused on curbing angiogenesis: the growth of new blood vessels.

Sense of smell or taste returns within six months for 4 out of every 5 COVID-19 survivors who have lost these senses, and those under 40 are more likely to recover these senses than older adults, an ongoing Virginia Commonwealth University study found.
Among 798 respondents to the ongoing COVID-19 smell and taste loss survey who had tested positive for COVID-19 and reported a loss of smell or taste, participants who were younger than 40 recovered their sense of smell at a higher rate than those older than 40, according to study results published in the American Journal of Otolaryngology last month. The VCU study requires survey participants to be 18 years or older.
Evan Reiter, M.D., medical director of the Smell and Taste Disorders Center at VCU Health and a co-investigator on the study, said the latest data show 4 in 5 participants, regardless of age, regained their smell and taste within six months.
“With our cohort, we did see about an 80% recovery rate in a six-month period or longer,” said Reiter, a professor and vice chair in the Department of Otolaryngology — Head and Neck Surgery at the VCU School of Medicine. “However, 20% is still a lot of people, given the millions that have been afflicted with COVID-19.”
What symptoms COVID-19 survivors experienced and what pre-existing conditions they had also offered insights into their recovery. Those with a history of head injury were less likely to recover their sense of smell. Recovery was also less likely for those who had shortness of breath during COVID-19. However, those with nasal congestion had a higher likelihood of smell recovery.
“Increased likelihood of recovering smell in subjects with nasal congestion stands to reason simply because you can lose your sense of smell because you’re badly congested and odors can’t get into your nose,” Reiter said. “Certainly a subset of those people who are congested might have just lost their sense of smell because they were badly congested, rather than because of nerve damage due to the virus, as in other cases.”
There have been more than 230 million cases of COVID-19 worldwide, according to the World Health Organization. If estimates from the survey reflect populations worldwide, more than 20 million people could have lingering loss of smell or taste more than six months after their COVID-19 diagnosis.

In a new paper, researchers at the University of Illinois Chicago report that a drug approved for treating patients with autoimmune disease helped to prevent lung damage and death in mice infected with the SARS-CoV-2 virus, which causes COVID-19 in humans.
The results of their study provide strong evidence that inflammatory lung vascular leakage — or leaky lungs — is a key feature of COVID-19 illness. Vascular leakage can be caused by severe inflammation and results in a buildup of fluid in the lungs, which interferes with oxygen uptake. Mice infected with SARS-CoV-2 showed very clear and early signs of leakage from the blood vessels of the lung.
The research also suggests targeted drug treatments that suppress only select immune system pathways, like the rheumatoid arthritis drug used in the study that targets the molecular receptor called IL-1, might be a more suitable therapy for COVID-19 patients than drug treatments that suppress the entire immune system.
The study was led by senior author Asrar Malik, head of the department of pharmacology and regenerative medicine at the College of Medicine, and by co-senior author Jalees Rehman, professor of medicine in the department of pharmacology and regenerative medicine.
“With COVID-19, we need to strike a balance. On the one hand, we need a strong immune system to eliminate the virus. On the other hand, several studies suggest that in patients with severe COVID-19, the immune system can go overboard and even cause damage to our own body,” Rehman said. “So, while we need the immune system to work efficiently, we also need to prevent it from becoming hyperactive and causing collateral damage.”
The need for balance is why the UIC researchers decided to study the effects of a drug that works on only one targeted immune system pathway and see if that would help prevent SARS-CoV-2-induced leaky lungs.

New research published in The Journal of Physiology has shown that ketone supplements may be a novel therapeutic strategy for protecting and improving brain health in people with obesity.
People with obesity are known to be at a higher risk of developing cognitive impairment and neurodegenerative diseases.
This new study found that giving a ketone supplement three times a day for 14 days enhanced blood flow to the brain and improved aspects of cognitive function, like working memory and processing speed, in adults with obesity.
Supplements specifically containing the ketone body beta-hydroxybutyrate (B-OHB) that are safe for human consumption are relatively new and have mostly been investigated for physical performance (in sports and military settings).
It has previously been shown that ketone supplements are beneficial for older adults with mild cognitive impairment (MCI) and dementia.
In this study, the researchers have extended these findings by demonstrating that ketone supplements may be a novel therapeutic strategy for protecting and improving brain health in people with obesity, who are at risk of developing neurocognitive impairment.

Research from pharmacologists at the University of Sydney provides new insights into how cannabis extracts may work to treat epilepsy.
The study for the first time reports that three acidic cannabinoids found in cannabis reduced seizures in a mouse model of Dravet syndrome, an intractable form of childhood epilepsy.
The study has been published in the British Journal of Pharmacology.
“From the early nineteenth century cannabis extracts were used in Western medicine to treat seizures but cannabis prohibition got in the way of advancing the science,” said Associate Professor Jonathon Arnold from the Lambert Initiative for Cannabinoid Therapeutics and the Sydney Pharmacy School.
“Now we are able to explore how the compounds in this plant can be adapted for modern therapeutic treatments.”
In 2015, Barry and Joy Lambert made an historic donation to the University of Sydney to advance scientific research on medicinal cannabis and cannabinoid therapeutics. Barry and Joy’s granddaughter Katelyn suffers from Dravet syndrome, which features frequent seizures and causes delays in cognitive and motor development. Conventional therapies often do not provide adequate seizure control and patients have a reduced quality of life.

Forget bedrest, research from Edith Cowan University (ECU) has shown exercise may be a key weapon in cancer patients’ battle against the disease.
Exercise causes muscles to secrete proteins called myokines into our blood — and researchers from ECU’s Exercise Medicine Research Institute have learned these myokines can suppress tumour growth and even help actively fight cancerous cells.
A clinical trial saw obese prostate cancer patients undergo regular exercise training for 12 weeks, giving blood samples before and after the exercise program.
Researchers then took the samples and applied them directly onto living prostate cancer cells.
Study supervisor Professor Robert Newton said the results help explain why cancer progresses more slowly in patients who exercise.
“The patients’ levels of anti-cancer myokines increased in the three months,” he said.

A team of Mass Eye and Ear Scientists led by Albert Edge, PhD, working with research fellow Yushi Hayashi, MD, PhD, has identified the mechanism that can lead to deafness in the rare syndrome, Norrie disease. The researchers found that the Norrie Disease Protein (NDP), which is lacking in patients with the rare disease, is essential for the maintenance and survival of hair cells in the cochlea, the cells responsible for hearing.
They also found that a pathway believed to be vital for hair cell regeneration, known as the Wnt pathway, could mimic the effects of NDP by restoring hearing in deaf mice with Norrie Syndrome. This method and another technique that overexpressed NDP in nearby cells were both able to prevent and rescue hearing loss.
The new discoveries, published in the September 28 issue of PNAS, may lead to promising treatment targets for the incurable disease and other forms of profound hearing loss.
Norrie disease is an inherited disorder caused by more than 100 different mutations in the NDP gene that can lead to blindness, deafness and intellectual disability in males. While infants with Norrie disease are born blind, their hearing is typically normal at birth and progressively deteriorates to profound loss by an average age of 12 years. The hearing loss can be particularly devastating for the families with an affected child.
Previously, researchers had thought that vascular issues caused by Norrie disease are what led to vision and hearing loss. However, the new findings suggest a lack of NDP is what causes hair cells to deteriorate and ultimately leads to deafness.
By learning more about the role of this protein in hair cell loss, the researchers were able to target two pathways that effectively prevented and reversed hearing loss in mouse models with Norrie disease.

The development of alveoli in organoids derived from mammary-gland tissue follows the same physical principles as the formation of discrete droplets in a water jet.
Many of the organ systems found in animals exhibit highly complex structures, which are essential for their various functions. How such structures develop during embryonic development is a central question in biology. Physicists led by Erwin Frey (Professor of Statistical and Biological Physics at LMU Munich) and Andreas Bausch (Professor of Cellular Biophysics at the Technical University of Munich) investigated this fundamental problem using mini-organs termed organoids as their experimental system. The team focused on the spherical ‘alveoli’ in which the ducts of the lactating mammary gland terminate. The study demonstrated in detail that these alveoli form according to the same principles as droplets in a jet of water emerging from a hose.
The experimental work was carried out in Bausch’s laboratory and used mammary-gland organoids grown in culture from excised human tissue. Organoids are three-dimensional model systems that exhibit many of the physiologically relevant properties of the organ from which they originated. Thus, mammary-gland organoids form ducts that branch into clusters of smaller tube-like structures, each of which ends in a spherical sac or alveolus. This architecture is typical of the lactating human mammary gland, but it is also found in many other organs including the lung. Bausch and his group succeeded for the first time in following the growth dynamics of the mini-organs over several days via time-lapse microscopy. In addition, they investigated the micromechanical response of the developing tissue to the localized, laser-induced ablation of cells.
Using this strategy, the researchers were able to link the formation of the spherical alveoli to a change in the direction of movement of the cells in the developing tissue. The cells in each tubule are constantly in motion, pulling on their immediate neighbors. At first, they collectively migrate back and forth along the walls of the tubules. “But at some point, the cells at the tips of the tubules begin to follow a rotational course. This change in behavior, associated with the interactions between neighboring cells, then propagates posteriorly until all the cells near the tip of a branch begin to rotate as a collective,” says Andriy Goychuk, a member of Erwin Frey’s research group and joint first author of the publication. His colleagues Pablo Fernandez and Benedikt Buchmann in Andreas Bausch’s group, who performed the ablation experiments, explain what happens as follows. “The cells no longer exert the same force in all directions, which results in an alteration in their trajectories. While the cells that alternate between forward and backward movement exert more force in the direction of the axis of the tube than around its circumference, that is no longer the case for the cells that follow a rotational course. Thanks to the greater tensile stress along the circumference, the tip of each tube develops into a spherical protrusion.”
According to the authors, the mode of formation of the spherical protrusions is analogous to the mechanism that is responsible for the formation of drops in a water jet. Like the cells in the developing organoid, the surface of the water jet is under tension. All objects that are subjected to a tensile force try to minimize their surface. Since the surface area of a sphere is less than that of a cylinder, the water jet breaks up into discrete droplets — and in the mammary-gland tissue, the rotation of the leading cells alters the balance of forces in the tubular branches in such a way that they become unstable, as in the case of the water jet, and form spherical protrusions. “This theoretical model provides an important framework for the analysis of more complicated geometrical transformations in biological tissues — such as those that occur during the development of the salivary glands, the pancreas, the kidney and the lung,” says Frey.
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