Head and Neck Cancer Treatment: Photoimmunotherapy “Lights Up” the Future of Cancer Therapy | GeneOnline News

Head and neck cancer is the seventh most common cancer in the world. The tumor covers the mouth, throat, and nasal cavity, and the symptoms and treatment vary according to the location of the tumor. However, due to the unique nature of this cancer, head and neck cancer is one of the most difficult cancers … Read more

Exploring the inner world of cells, new micro-antennas can see disease progression from a cellular perspective | GeneOnline News

The application and development of micro-robots in the medical field continues to keep pace with the times. In “Nature-Communications” (Nature Communications) in the latest paper in the journal,MIT(MIT) team has demonstrated for the first time a tiny antenna that can operate wirelessly inside living cells. Since cells are the foundation of biological systems, the team … Read more

Why does fear linger? Deciphering the new world of the brain | GeneOnline News

Researchers at Linköping University in Sweden have discovered a biological mechanism that may increase the strength of fear memory storage in the brain.The research in mice, published in the journal Molecular Psychiatry, publishes new knowledge about the mechanisms behind anxiety and identifiesanxietyand common mechanisms behind alcohol dependence. There may be a cure for HIV sooner … Read more

In addition to aging, lack of ‘young’ protein may also lead to aging eyes | GeneOnline News

Retinal aging may cause many ophthalmic diseases. In a new study, the National Eye Institute (NEI) used a mouse model to determine the role of pigment epithelium-derived factor (PEDF) in retinal aging. This finding may lead to the emergence of related treatment measures in the future.

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The importance of pigment epithelium and PEDF recycling

The retina is composed of multiple layers of cells that work together to detect and process the received light signal. The photoreceptors of the photoreceptors are located in the retinal pigment epithelium (RPE), and after receiving light, the photoreceptor outer segment (POS) ) tip will wear out and fall off, and the RPE must recycle the cell debris and supply the ingredients again, otherwise these photoreceptors will lose their ability to make new segments, resulting in the eventual inability to perceive light, and the RPE must also provide nutrients, otherwise the photoreceptors may also die.

In addition to closely interacting with photoreceptors, RPE also secretes a large number of factors and signaling molecules to communicate with surrounding tissues, and PEDF is one of them. Because PEDF is abundant in young retinas, but will gradually decrease in the process of aging, PEDF was also jokingly called a “youth” protein in the past, but in fact, is the reduction of PEDF causing retinal aging, or aging has an impact on the retina , researchers have been unable to determine.

It is well established that aging or dysfunction of the RPE is responsible for vision loss in cases of age-related macular degeneration (AMD) and some retinal dystrophies. Previous studies have shown that PEDF can protect retinal cells against cell damage and abnormal growth of retinal blood vessels, and the researchers were more curious whether PEDF could also help prevent aging in RPE.

PEDF is a driver of retinal ageing-related changes

In order to confirm the actual effect of PEDF on the retina, the research team found that the lack of sprinkle1 Retinal cell structure was examined in a mouse model of a gene that causes defects in PEDF production. It was found that in addition to the enlarged nuclei of RPE cells, indicating a likely change in the way DNA stacks,sprinkle1 The deletion also increased expression of four genes associated with aging in the RPE, while levels of the PEDF receptor were also significantly lower than normal.

Binding of PEDF to its receptor PEDF-R stimulates the breakdown of lipid molecules, which is also a key process part of POS recovery. In the absence of both, the result is the accumulation of raw lipid molecules and other POS components in the RPE, similar to Gene expression changes and RPE metabolic defects were also found in aging retinas. It can be said that this study is the first to show that just removing PEDF can cause a series of genetic changes like retinal aging.

It is worth mentioning that although both PEDF and its receptor are mainly produced by RPE cells, the latter is produced by RPE cells. Pnpla2 gene expression, but with Serpinf1 Deficiencies of both were also reduced, which suggests that there appears to be a PEDF-related feedback loop that maintains levels of PEDF-R and lipid metabolism in the RPE, according to study author Dr. Ivan Rebustini.

While PEDF-negative mouse retinas appear normal at first glance, these new findings show that PEDF has an important protective role in protecting the retina from trauma and age-related wear and tear. “We’ve always been curious about whether PEDF loss is driven by or is driving aging, and the findings, particularly in part with clear links to altered lipid metabolism and gene expression, reveal that PEDF loss is a driver of retinal ageing-related changes. factor.”

Further reading: Electrical stimulation of the surface of the eye can relieve depression and dementia?

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Plant protein linked to human cancer cell growth? | GeneOnline News

One might not expect that humans and the plant kingdom share an average of 20-50% of DNA.And just as unexpectedly, by studying how plant growth is controlled, it is possible to discover potentialcancer treatmentmethod.Although unimaginable, scientists at the Cold Spring Harbor Laboratory in New York recently discovered aproteinactivity may be related tocancer cellgrowth is related.

Life began with RNA theory gains new support

Research progress of plant protein

Established in 1890, Cold Spring Harbor Laboratory has outstanding research results in the fields of cancer, neuroscience, plant biology, and quantitative biology. Their initial goal was to advance agriculture through this research, but they made unexpected discoveries along the way.

The team’s results describe how proteins called UBP12 and UBP13 help regulate a protein called cryptochrome 2 (CRY2)photoreceptor. CRY2 is a photoreceptor that senses blue light and long-wave ultraviolet light (UVA, wavelengths between 320-400 nanometers) and is responsible for controlling plant growth. Specifically, in plants, UBP12 and UBP13 proteins help degrade CRY2 photoreceptors. In low light conditions, the concentration of these two proteins increases, allowing CRY2 to be degraded more quickly, which can promote the growth of long stems, or help plants get more light.

The researchers also found that simply increasing the concentrations of UBP12 and UBP13 replicated the above effects. Because plants need the right amount of CRY2 to control when they grow and flower, adjusting the concentration of these proteins may be useful if farmers or botanists need to increase crop yields or delay flowering. Understanding the mechanisms behind plant growth could lead to a range of potential economic and medical benefits.

Dr Pedmale said: “We already have a way of understanding plant growth – we can manipulate plant growth just by manipulating two proteins. We have found a way to actually increase the production of flowers. Flowering is a necessary process for obtaining food. If there are no flowers, there is no grain, no rice, no wheat, no corn.”

Application of plant protein in human body

In humans, the equivalent of CRY2 is HCRY (Human Cryptochrome 2).The protein is a flavoprotein, which is also sensitive to blue light and has the ability to regulate the human body.daily routinefunction. HCRY1 and HCRY2 proteins form a negative feedback loop by acting as transcriptional repressors.

The sequence of HCRY2 is highly conserved throughout the animal kingdom, which means that this protein is very important in animal life. When coding errors occur, people suffer from sleep disturbances. This problem is in turn linked to disruption of circadian rhythms and, in the long run, increased rates of cancer, diabetes and heart disease. In-depth study of human CRY proteins may help make human circadian rhythms more tolerant of changes and allow people to better manage modern life without causing disease.

Dr. Pedmale’s lab and their colleagues at Cold Spring Harbor Laboratory hope that this series of findings will bear fruit in cancer research and growth management of other species.

Author: Eduardo Longoria
Compilation: Richard Chou
original:Why CRY2 matters: Studying Control of Plants and Human Growth – GeneOnline News

Further reading: Gene editing “Swiss knife”? Editing proteins from archaea, half the size of CRISPR!

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Alzheimer’s memory loss is related to cerebrovascular changes? | GeneOnline News

Alzheimer’s diseaseConsidered to be a disease of brain cells, in addition to being known to be associated with β-amyloid (β-amyloid) plaque deposition, the association with cerebral blood vessels has also begun to attract attention in recent years.

In a new study published in the Proceedings of the National Academy of Sciences, a U.S. research team revealed previously unknown changes in blood vessels in the brain, leading to a breakthrough in the understanding of Alzheimer’s disease and the development of new drugs Offers a whole new angle of entry.

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Aβ1-40 accumulation leads to narrowing of leptomeningeal arteries

The pathological cause of Alzheimer’s disease is still unknown, but there is growing evidence that the blood supply to the brain is also affected in the process, and researchers at the University of Manchester have found that this phenomenon may be related to beta- An isoform of amyloid, Aβ1-40, is associated with accumulation in the walls of arterioles.

The surface of the brain is covered with small arteries called pial arteries, which control the blood and oxygen supply to the brain. Once these arteries narrow for a long time and reduce blood flow for some reason, the brain cannot get enough nutrients. This is one of the reasons why people with Alzheimer’s disease experience memory loss.

In experiments with mice, when the researchers looked at pial arteries in aged mice that had excess Aβ1-40 production due to Alzheimer’s disease, they found that these arteries were significantly narrower than those in healthy mice. The researchers noticed that the main reason for the narrowing of blood vessels is that Aβ1-40 turns off a protein called BK in the cells lining blood vessels, which when functioning normally, sends a signal to widen the arteries.

To determine that Aβ1-40 was blocking BK from working properly, the team soaked pial arteries from young, healthy mice in Aβ1-40 and measured the signal from the BK protein an hour later. The results showed that Aβ1-40 did attenuate these signals and cause the arteries to narrow.

Will research lead to new treatments for Alzheimer’s?

The researchers plan to further investigate how Aβ1-40 blocks the BK protein, so that researchers can develop and test drugs that seek to improve the function of brain blood vessels damaged by the disease, thereby slowing the memory loss caused by the progression of Alzheimer’s disease. .

Lead researcher Dr Adam Greenstein, Senior Clinical Lecturer in Cardiovascular Sciences at the University of Manchester, pointed out that in the past research related to Alzheimer’s disease has mostly focused on the nerves in the brain, but so far more than 500 drugs have been tried to treat Alzheimer’s disease. None of the drugs has shown successful results so far.

The research team believes that this study is an important step in understanding Alzheimer’s disease. In addition to showing how Alzheimer’s affects small blood vessels, it also opens the door to new research into finding effective treatments for Alzheimer’s.

According to WHO statistics, more than 55 million people worldwide are currently suffering from dementia, of which Alzheimer’s disease may be responsible for nearly 70% of the cases. The numbers are expected to continue to rise as the population ages. Professor Metin Avkiran, deputy medical director of the British Heart Foundation, said the discovery could lead to a much-needed treatment for this devastating disease.

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Another breakthrough in T cell therapy! Key synthetic IL-9 receptor expected to ease the need for chemoradiotherapy? | GeneOnline News

T cell therapy is an innovative option to fight cancer tumors. However, before patients can receive treatment, they must first destroy the original immune system in the body through chemotherapy or radiation therapy. The potential for new functions of proliferating T cells may change in the future.

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Synthetic receptor helps T cells outperform existing immune system and fight cancer more effectively

In the latest study in “Nature”, a team of researchers from the University of California, Los Angeles (UCLA), Stanford University, and the University of Pennsylvania describe a T cell engineered with a synthetic interleukin-9 (IL-9) receptor that can be used in different It can complete the work under the condition of chemotherapy or radiotherapy, and has a significant anti-tumor effect on tumors in mice.

The synthetic IL-9 receptor engineered T cells were designed in the laboratory of Dr. Christopher Garcia at Stanford University. The team found that signaling through the synthetic receptor appears to confer new functions on T cells, and in the case of the synthetic IL-9 receptor, not only helps the engineered T cells defeat the existing immune system, but also kills cancer more efficiently cell.

In view of the common side effects after chemotherapy and radiotherapy, the research team believes that with this technology, it may be possible to re-evaluate the necessity of using chemotherapy and radiotherapy to clear the immune system before T cell therapy in the future. “This discovery is like opening the door for us to deliver T cells like a blood transfusion,” said study author Antoni Ribas, a senior research fellow at UCLA.

Synthetic IL-9 receptor gives T cells mixed properties

The new research stems largely from a paper by Ribas and Garcia in 2018, in which the two focused on the concept of how to use a synthetic version of IL-2 to stimulate the synthesis of transgenic-matched IL-2 receptors. body T cells. With this system, even after injecting T cells into a patient, medical teams can manipulate T cells through synthetic cytokines for treatment without affecting other cells in the body.

Inspired by this 2018 study, Anusha Kalbasi, MD, UCLA, and colleagues were also interested in testing other versions of the synthetic receptor, focusing on other cytokine signals that also come from the common gamma chain : on IL-4, IL-7, IL-9 and IL-21.

The team quickly noticed the peculiarities of IL-9. Unlike other cytokines that share gamma chains, IL-9 signaling is not active in native T cells, while synthetic IL-9 signaling gives T cells a combination of stem and killer cell properties, Kalbasi points out Significantly more powerful against tumors. In one of the cancer models, synthetic IL-9 receptor T cells even managed to cure more than half of the treated mice.

According to the research team, this therapy has shown its full potential in multiple systems.In mouse models of pancreatic cancer and melanoma, two difficult-to-treat cancers, the team used natural T-cell receptors orChimeric Antigen Receptor (CAR) T cellsTo target cancer cells, either injecting cytokines into mice or directly into tumors has shown success, and as research continues, it may be possible to overcome barriers in solid tumor treatment in the future.

Further reading: Combining T-cell immunotherapy with CRISPR, Editas, Immatics to strengthen anti-cancer drugs!

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Oocytes will remember! Pre-pregnancy hyperglycemic environment increases infant risk of diabetes | GeneOnline News

Diabetes is a chronic disease. There is currently no cure. It requires long-term adjustment of diet, living habits and drug control to maintain normal blood sugar. Therefore, early prevention of diabetes has become an important public health issue. It is known that having a family history of diabetes, or having gestational diabetes when the mother is pregnant, is a risk factor for developing diabetes.

A recent paper published in “Nature”, more from the perspective of epigenetics, pointed out that pre-pregnancy exposure to high blood sugar environment will make oocyte DNA experienceMethylation modification, thereby increasing the risk of developing chronic diabetes in young children. This study, published by Zhejiang University School of Medicine in China, brings a new perspective on diabetes prevention and control, which is different from gestational diabetes risk factors. This study shows that by controlling the blood sugar environment in the mother’s body before pregnancy, diabetes can be fundamentally prevented in the offspring.

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High blood sugar environment increases the risk of diabetes in offspring

In order to understand how pre-pregnancy environmental factors in women change the probability of developing diabetes in offspring, Dr. Huang Hefeng’s research team from Zhejiang Medical College established a female mouse model to exclude the continuous impact of hyperglycemia on embryonic and fetal development. In vitro fertilization, and the embryos are transferred into healthy mice to grow into offspring and observe whether their metabolic characteristics are abnormal.

It was found that the offspring showed symptoms of glucose intolerance (impaired glucose tolerance), that is, a high blood sugar environment increased the offspring’s susceptibility to chronic diabetes. The research team further proposed a more in-depth molecular mechanism to explain the reason for the increased incidence of offspring.

Image source: Professor Huang Hefeng’s research team

Oocyte methylation modification is the culprit

The reason why the offspring of mice are prone to diabetes is due to the lack of TET3 (TET methylcytosine dioxygenase 3) protein in the oocytes of the mother mouse. TET3 is related to the regulatory mechanism of chronic disease. The team pointed out that the high blood sugar environment in female mice can cause insufficient TET3 concentration, which in turn leads to insufficient demethylation or hypermethylation of fertilized eggs.

As for the association between TET3 deficiency and abnormal insulin secretion, another important gene is involved GCK(glucokinase gene)。GCK Involved in insulin secretion, caused by hypermethylation during zygote replication and division GCK Low gene expression, together with insufficient insulin secretion, increases the susceptibility of offspring to diabetes as they age.

Pre-pregnancy blood sugar control is a new strategy for diabetes prevention and treatment

Not only was this study confirmed in a mouse model, but the clinical manifestations of some pregnant women with diabetes also support this hypothesis. The team obtained samples of immature oocytes from diabetic patients from Hangzhou and Shanghai hospitals in China, and also found that TET3 protein deficiency,GCK The phenomenon of low gene expression.

This study is different from the previous focus on the risk factors of gestational diabetes in pregnant women, and more importantly, it points out that the pre-pregnancy blood sugar environment can bring disease risk through epigenetic modification. Professor Huang Hefeng, the project host, said that the transgenerational genetic phenomenon caused by the reproductive environment provides a new intervention strategy for the prevention and control of chronic diabetes.

Further reading: FDA approves the first case in ten years!Eli Lilly’s diabetes drug GIP/GLP-1 receptor activator approved

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