Humans have salamander-like ability to regrow cartilage in joints

Humans have salamander-like ability to regrow cartilage in joints

Recently, scientists at Duke Health have discovered that unlike popular belief, human cartilage have a tendency to repair on its own through a process of limb regeneration similar in salamander and zebrafish. The research has been published in the journal of Science Advances on Oct 9.

Researchers found that the mechanism of the self repair was more robust in ankle joints in comparison to hips. These findings have paved a new path for developing effective treatment methods for osteoarthritis and other associated diseases across the globe.

“We believe that an understanding of this ‘salamander-like’ regenerative capacity in humans, and the critically missing components of this regulatory circuit, could provide the foundation for new approaches to repair joint tissues and possibly whole human limbs,” said Virginia Byers Kraus, M.D., Ph.D., (Senior author).

Taking a closer look

To understand the entire mechanism of limb regeneration the researchers focused on studying the age of certain proteins. For this, they analyzed the internal molecular clocks integral to amino acids, which convert one form to another. This conversion was quite predictable which helped scientists to establish further details.

They found that newly created protein had very less or no amino acid conversion while the old proteins had many. Using mass spectrometry they analyzed whether these proteins in human cartilage were young, middle-aged or old. Studies showed that the age of cartilage is mainly dependent on its location in the human body. For example, cartilages in the ankle area are found to be young, in kneed its middle age, wherein hips area it was quite old.  This correlation between the location and age of the cartilage indicates how limb regeneration and repair occur in some organisms, wherein the apex parts o the body such as tails or legs showed rapid regeneration. Additionally, it also explains why people with knee or hip injury take more time to recover in comparison to an ankle injury which recovers quicker.

To understand the process in detail, researchers tried to study molecules like microRNA involved in this process. They observed that the microRNA were more active among animal well known for their limb regeneration activity such as lizards, fish, salamanders and more.

These microRNA are also known to be present in humans, offering natural competence of tissue repairs. It is higher in the top layers of cartilage in comparison to the deeper layers.

“We were excited to learn that the regulators of regeneration in the salamander limb appear to also be the controllers of joint tissue repair in the human limb,” Hsueh said. “We call it our ‘inner salamander’ capacity.”

The researchers said microRNAs could be developed as medicines that might prevent, slow or reverse arthritis.

“We believe we could boost these regulators to fully regenerate degenerated cartilage of an arthritic joint. If we can figure out what regulators we are missing compared with salamanders, we might even be able to add the missing components back and develop a way someday to regenerate part or all of an injured human limb,” Kraus said. “We believe this is a fundamental mechanism of repair that could be applied to many tissues, not just cartilage.”

Scientists Help Immune System Find Hidden Cancer Cells

Scientists Help Immune System Find Hidden Cancer Cells

Cancer is a widely studied topic in bioscience research but yet remains to be mostly unknown and difficult to treat. However, the recent developments in cancer research over the past decade have helped the scientific community to come up with effective treatment methods. But still, one of the most common problems faced in treating cancer cells is difficulty in locating them for efficient targeting. Recently, scientists from Yale University have developed a new system that can help our immune system find the hidden cancer cells and kill them. The research has been published in Journal Nature Immunology.

Why this study holds importance?

It is a known fact that there exists a number of immunotherapies for treating cancers. But these therapies have certain shortcomings as they either don’t work on all patients or are inefficient in different cancer types. The major reason behind this is the failure of these therapies in identifying the cancer cells which reduces their effectiveness. This highlights an urgent need for a more targeted approach that can help curb the menace of cancer.

The development of a new system by scientists in the present study is considered to overcome the drawbacks of the earlier immune therapies. Researchers report that upon testing the new system in mice it has shown positive response against the melanoma, triple-negative breast, and pancreatic tumors, even for those tumors which are situated at a distant location from the primary tumor.

“This is an entirely new form of immunotherapy,” said Sidi Chen, senior author.

How the new system – MAEGI works?

The researchers developed a new system to target the cancer cells which combines the viral gene therapy and CRISPR based gene-editing technology. Unlike the traditional method of searching and making edits at the DNA level by incorporation of new genes, the present system uses a much more targeted approach.

The new system named as MAEGI stands for Multiplexed Activation of Endogenous Gene as Immunotherapy. This system works by searching numerous cancer-causing genes, marking their location by mimicking GPS and subsequently intensifying the signal of these locations for precise targeting.

For instance, you can consider that the new system dresses up the tumor cells in a unique manner that can be easily identified by the immune system of our body and eventually eliminate them. For this, the cold tumors cells lacking any immune cells are converted into hot tumors cells which are packed with tons of immune cells.

“And once those cells are identified, the immune system immediately recognizes them if they show up in the future,” Chen said. The new system, in theory, should be effective against many cancer types, including those currently resistant to immunotherapy, he said.

The researchers will be further optimizing this system to make the manufacturing process easier. Once optimization is done it will be subjected to clinical trials in potential cancer patients.

No wonder that cancer is a rising menace in the present world. Though many therapies are available we still need highly effective methods to treat cancer. The development of the immunotherapy-based system has given rise to a ray of hope for a more effective and proficient treatment that not only treats primary tumor cells but also the distant ones. Let’s look forward to this new development and hope for the best outcomes in subsequent clinical trials.

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Mucus is more just than a physical barrier for microbes

Mucus is more just than a physical barrier for microbes

Do you know that the mucus in our body has a much greater role to play than just forming a physical barrier for microbes? Recent research by scientists at MIT reveals that the glycans in mucus can hinder communication between microbes rendering them harmless by forming an infectious biofilm.

The researcher Katharine Ribbeck has been studying the underlying biochemistry of mucus for over a decade. “Mucus piqued my interest because it is just this vastly understudied material that occupies a large surface area in our body,” – Ribbeck.

On average, a person produces a liter of mucus every day, which is used by our body to protect against harmful microbes. Mucus lines numerous organs in our body such as digestive tracts, urinary tracts, and lungs. It acts as a lubricant and physical barrier blocking the microbial invasion.

The study focuses on unwinding the role of mucins in mucus. Mucins are proteins densely packed with chains of sugar. Till date, very little research has been done in this area. This highlights the importance of the present study as it lays the foundation for further studies to understand the role of mucus in our body.

Unwinding the role of glycans

The scientists were very much interested in understanding the role of glycans in regulating microbial behavior. These glycans are known for attaching to proteins known as mucins, responsible for the characteristic gel-like nature of the mucus. To gain deeper insights scientists subjected the isolated glycans against Pseudomonas aeruginosa, which is a pathogen causing infection among people with compromised immune system. The findings showed that the mucin glycans rendered the microbes to become less harmful by altering their behavior. For example, the microbial cells didn’t show any toxin production, killing of host cells or attaching to the surface of host cells, and expression of genes playing a role in bacterial communication. Researchers further supported their finding by showing the role of mucin glycans in reducing the bacterial proliferation in Pseudomonas infected wounds.

Future prospects of the discovery

The present study has unraveled the important role of mucus in overcoming the bacterial infection. To take this ahead, researchers are now looking forward to developing artificial mucus which can provide new insights to treat diseases and infections stemming from mucus. The researcher (Ribbeck) said, “Harnessing the powers of mucus could also lead to new ways to treat antibiotic-resistant infections because it offers a complementary strategy to traditional antibiotics”.

“What we find here is that nature has evolved the ability to disarm difficult microbes, instead of killing them. This would not only help limit selective pressure for developing resistance because they are not under pressure to find ways to survive, but it should also help create and maintain a diverse microbiome,” – Ribbeck


Cancer causing mutation in Dark Matter of genome

Cancer causing mutation in Dark Matter of genome

According to the World Health Organisation (WHO), cancer is one of the major leading causes of death worldwide. The statistics show 9.6 million deaths in 2018 due to cancer, showing how severe is the issue globally. This highlights that the development of new research in cancer to overcome its perils is an urgent need of time. Recently, an Ontario based research group has carried out breakthrough research which can change the way cancers were targeted. They have discovered novel cancer-causing mutation in the non-coding region or junk region of the genome which is also referred to as the “dark matter”. Two related studies dealing with the identified mutation have been published recently in Nature.

“Non-coding DNA, which makes up 98 percent of the genome, is notoriously difficult to study and is often overlooked since it does not code for proteins,” – Dr. Lincoln Stein, co-lead of the studies, Head of Adaptive Oncology at the Ontario Institute for Cancer Research (OICR)

How new mutation can help target cancer

In the present study, scientists have identified a mutation in U1-snRNA (small nuclear RNA) which can be used to target cancer. U1-snRNA is known to play a role in tele-scripting wherein it suppresses the polyadenylation process and premature cleavage of transcripts making them available whenever a cell needs. The regions of DNA containing polyadenylation signals are sheltered by U1-snRNA to protect the nascent transcript, allowing the transcription process to continue. Any mutation in U1-snRNA will significantly alter its functioning leading to conditions like cancer.

“By carefully analyzing these regions, we have discovered a change in one letter of the DNA code that can drive multiple types of cancer. In turn, we’ve found a new cancer mechanism that we can target to tackle the disease.” – Dr. Lincoln Stein

The study shows that this mutation can disrupt the RNA splicing process, which will hinder the transcription of cancer-causing genes in the human genome. This provides a completely new approach to targeting cancer that can help in developing new treatment methods.

One of the potential treatment methods is to retune the use of existing drugs. This will help in bypassing the several stages of early drug development processes, making research available for clinical trials at a fast pace.

Further studies revealed that U1-snRNA mutation is present in a wide range of cancers such as subtypes of brain cancer, medulloblastoma, chronic lymphocytic leukemia (CLL) and hepatocellular carcinoma. Besides this, the presence of U1-snRNA mutation has been implicated in several other diseases involving misfolded protein. This signifies the important role of U1-snRNA and its mutation in the transcription process and the potential it holds to develop methods for subsequent cancer targeting.

“Our unexpected discovery uncovered an entirely new way to target these cancers that are tremendously difficult to treat and have high mortality rates,” – Dr. Michael Taylor, co-lead of the studies.

“We’ve found that with one ‘typo’ in the DNA code, the resultant cancers have hundreds of mutant proteins that we might be able to target using currently available immunotherapies.”

“This discovery is an example of how OICR is working together with partners in Ontario and across the world to support cutting-edge research that can be used in the development of precision therapies for cancer patients worldwide,” says Dr. Laszlo Radvanyi, President and Scientific Director of OICR.

Aspirin can reduce air pollution effect on lungs

Aspirin can reduce air pollution effect on lungs

Aspirin is widely used for treating headaches but do you know it can also have functional value in relieving your lungs from pollution damage? Recent research by scientists from Columbia Mailman School of Public Health, Boston University School of Medicine and Harvard Chan School of Public Health has revealed the potential aspects of aspirin in reducing the impact of pollution on lungs. The research has been published in the American Journal of Respiratory and Critical Care Medicine.

Pollutants in the air can harm your body by causing severe damage to the lung cells. This mainly includes inflammation and irritation in the cells which can become more serious if not taken care of. It does make sense now why researchers choose aspirin as an agent to curb the menace of pollution. Aspirin is a non-steroidal anti-inflammatory drug (NSAIDs) which has a defensive effect in response to inflammatory reactions in the body.

In the present research, scientists collected the data of more than 2000 male veterans belonging to the Boston area with an average age of 73 years. The functionality of the lungs of this cohort was evaluated to gain better insights for further comparative analysis (since 1960). Moreover, the data for air pollution was also analyzed (since 1955) regularly.

Researchers compared the functionality of the lungs of volunteers under the influence of NSAIDs and those who are not. They observed that the group with exposure to NSAID showed the reduced impact of particulate matter and black carbon on the lungs in comparison to those without NSAID administration. The study also considered other factors such as the health of the volunteers and smoking habits to come up with precise result analysis. The results were found to be consistent throughout the study sessions for all weekly air pollution measurements from the initial day of inspection until the day of the lung function test.

Researchers found that most of the volunteers consuming NSAID mainly used aspirin. This highlights the improved response observed among volunteers can be contributed by aspirin. However, other non-aspirin NSAIDs can also be explored to understand the overall effectiveness and association with a lung condition.

“Our findings suggest that aspirin and other NSAIDs may protect the lungs from short-term spikes in air pollution,” says corresponding author Xu Gao, a scientist in the Department of Environmental Health Sciences at the Columbia Mailman School. He added, “Of course, it is still important to minimize our exposure to air pollution, which is linked to a host of adverse health effects, from cancer to cardiovascular disease.”

The findings support the use of aspirin in overcoming the harm caused by pollution to the human lungs. Though the exact mechanism of working is not yet known, the study paves the path for the researcher to speculate and evaluate the role of NSAIDs in overcoming the inflammatory responses due to severe pollution exposure. Further detailed studies are needed to evaluate the impact and understand the mechanism at a molecular level.


COVID 19: A battle between heat and humidity Vs Sunshine

Enhanced Thermostability and Anticancer Activity in Breast Cancer Cells of Laccase Immobilized on Pluronic-Stabilized Nanoparticles

Laccases are mainly found in fungi and plants known for catalyzing oxidation reactions. They are often named as multi-copper enzymes having a wide range of applications across a multitude of biotechnological processes.  Though widely used the major challenge is the low stability of the free enzyme which often restricts its usability for industrial purposes.  The development of new methods that can enhance the enzymatic activity is a need of time. In the present study, immobilization of trametes versicolor laccase on pH-responsive, pluronic stabilized silver nanoparticles (AgNPsTrp) was carried out. The results showed enhanced activity if enzyme upon stabilization of AgNPsTrp with amphiphilic copolymer Pluronic F127, this helps in changing the microenvironment of active site facilitating the improved activity. The results were confirmed using circular dichroism (CD) and fluorescence spectroscopy. Further analysis showed that lowering the activation energy and expanding the temperature window for substrate hydrolysis can play a crucial role in improving the enzyme activity. No change in the behavior of the nanocomposite indicated the stability of the enzyme as normal with the absence of any aggregation after immobilization. The efficiency of the nanocomposite in breast cancer cells- MCF-7 was observed which showed inhibition of cell proliferation by promoting cell apoptosis and beta-estradiol degradation. Further, qRT- PCR experiments were conducted to understand the underlying molecular mechanism hindering cell proliferation. The analysis showed a reduced level of mRNA levels of the anti-apoptotic genes and enhancement in level of pro-apoptotic genes. For example, BCL-2 and NF-kβ, and increase in levels of pro-apoptotic genes like p53. The entire study provides a new way of enhancing the enzymatic activity of Laccases and extending its subsequent applications.


Cellulase and xylanase synergism in industrial biotechnology

Cellulase and Xylanase synergism in industrial biotechnology

In recent years, many studies have been carried out which shows tremendous benefits of biocatalyst when compared to chemical catalysts. Biocatalyst helps in carrying out reactions in an environment-friendly manner while providing a high level of selectivity, specificity, and low energy consumption.  Two of the most widely used enzyme as biocatalyst are cellulose and xylanase wherein the former is considered to be the 3rd highest used enzyme. Many of the industrial applications require the use of both the enzyme in combination such as bioethanol production, removal of ink in waste paper industries, food processing industries, feed processing, removal of fibers from the textile materials, pulp production, pharmaceuticals and many more. Cellulose and xylanase are mainly produced by microorganisms which increases the demands of these microorganisms in the market. In this review, are discussing the synergistic application of both cellulose and xylanase enzyme as biocatalyst in various industries. Besides this, the paper also discusses the potential applications and requirements of microbial systems producing such enzymes. The paper highlights the future prospects associated with the further development of these enzymes as a coherent part of various industrial processes.