Several studies have revealed the effects of cholesterol on human health

October 29, 2020 // --- This issue brings you the latest research advances in cholesterol and human health, and I hope readers and friends will enjoy it.
1. EMBO J: Revealing Cholesterol-25-Hydroxyase Inhibits SARS-CoV-2 and Other Coronavirus Infection Mechanisms Doi:10.15252/embj.2020106057.The new coronavirus SARS-CoV-2 causes coronavirus disease (COVID-19) in 2019 and is now raging globally.
the U.S. Food and Drug Administration (FDA) for the treatment of COVID-19.
several treatments are in clinical trials, the current standard treatments include the provision of recovery serums and anti-fever drugs to patients.
To speed up the search for new COVID-19 therapies, scientists are testing reusable drugs ---the known to be safe to use in humans because they have FDA approval to treat other diseases--- and the ability to reduce the virus infection.
In a new study, researchers at the University of California, San Diego School of Medicine found that cholesterol-25-hydroxylase (CH25H) removes cholesterol from cell membranes, preventing the coronavirus SARS-CoV-2 from entering host cells.
study was recently published in the journal EMBO Journal under the title "25-Hydroxylase reseds SARS-CoV-2 and other coronaviruses by depleting spiteing spite."
the paper is Dr. Tariq Rana, chair of the Department of Pediatric Genetics at the University of California, San Diego School of Medicine.
removing cholesterol from the cell membrane prevents SARS-CoV-2 from entering about six months ago, when Rana began the study, statins were not on Rana's consideration.
, his team was curious to see which genes in human lung cells would be "turned on" by SARS-CoV-2 infection.
Rana said a gene called CH25H is "hot."
ch25H encodes an enzyme that modifies cholesterol.
"I'm excited because we know that CH25H prevents the coronavirus from entering human cells, as opposed to HIV, Zika and other viruses.
"This is what happens in our cells: the enzyme activity of CH25H produces a modified cholesterol, 25-hydroxycholesterol (25-hydroxycholesterol, 25HC).
, 25HC activates another enzyme called ACAT, which is found in the endoblast network inside the cell.
ACAT then removes the cholesterol that can be obtained on the cell membrane.
this is a normal process that speeds up during some viral infections.
Rana and his team explored 25HC in the context of SARS-CoV-2 from multiple perspectives.
They explored in the lab what happens to human lung cells when they are first exposed to non-infectious viruses or live SARS-CoV-2 viruses that carry SARS-CoV-2 prickly proteins, the key to their entry into cells.
either way, the addition of 25HC inhibits the virus's ability to enter human lung cells -- almost completely blocking infections.
, "The difference between untreated human lung cells and 25HC-treated human lung cells is like day and night," rana.
" Although SARS-CoV-2 was originally combined with ACE2 binds to human lung cells, Rana's research shows that the virus also requires cholesterol (usually present in cell membranes) to fuse with human cells and enter them.
25HC removes a lot of this membrane cholesterol, which prevents the virus from entering.
in a similar way, statins are likely to help prevent or reduce the severity of SARS-CoV-2 infections because, while they are designed to remove cholesterol from blood vessels, they also remove cholesterol from cell membranes.
, the coronavirus is unable to enter human cells.
In our bodies, this happens a lot, so maybe we just need to use statins or other means to give it a boost to better fight some viruses," Rana said.
it's not the same as cancer immunotherapy--- sometimes it's better to arm the patient's immune system and let it clear the tumor itself, rather than attacking the tumor directly.
"Rana said, if 25HC can be developed as a treatment, it may work better as an antiviral drug than statins.
because it specifically affects cholesterol in the cell membrane, not in the whole body.
like many medications, statins can cause negative side effects, including digestive problems and muscle pain, and may not be a treatment option for many COVID-19 patients.
more importantly, although previous studies have shown that statins may also raise ACE2 levels, which may allow more viruses to enter human cells, Rana's team did not observe an increase in this level of the subject after 25HC was given.
statins have been approved by the FDA for human use, but 25HC is a natural product that is currently only available for laboratory research.
Rana team plans to continue optimizing 25HC as a potential antiviral drug.
much research is needed before human clinical trials can be conducted.
2. PNAS: Research has revealed the effects of cholesterol on cell membranes DOI: 10.1073/pnas.2004807117 For more than a decade, scientists have accepted that cholesterol (a key component of cell membranes) does not uniformly affect different types of membranes.
, a new study led by Rana Ashkar, an assistant professor in virginia tech's physics department, found that cholesterol does actually fit biophysical principles.
the findings, recently published in the journal PNAS, have far-reaching implications for the design of drug delivery methods and many other biological applications that require specific assumptions about the role of cholesterol in cells.
, "It's well known that cholesterol promotes closer molecular build-up in cell membranes," says Ashkar.
work, we have shown that, according to the laws of physics, cholesterol does cause membrane hardening at the nanoscale level.
these findings affect our understanding of the biological function of cholesterol and its role in health and disease.
" cell membrane is a thin layer of fat molecules that define cell boundaries and regulate a variety of biological functions, including virus transmission and cell division.
in order to achieve this function, the membrane structure should be able to bend and allow the shape to change.
this tendency to bend depends on the degree of accumulation of molecular structure units.
ashkar adds that tighter packaging can lead to harder membranes that cannot be easily bent.
, eggs, cheese and many other comfort foods contain high levels of cholesterol.
although too much cholesterol can damage the body, the amount of cholesterol in the cell membrane is absolutely necessary for normal cell function.
cholesterol levels are usually associated with a variety of disease conditions.
In addition to cholesterol, our cell membranes are mainly made up of lipids, a small fat molecule that is automatically assembled into a double structure when present in water - nearly 60% of the body is made up of water.
lipids and cholesterol together form a barrier that limits our cells and regulates their nutrient exchange.
at the molecular level, cholesterol has a smooth and rigid structure.
when it interacts with our cell membrane, it gets stuck between the lipids itself, resulting in a higher density of the membrane.
depending on the structure-attribute relationship, this naturally causes the membrane to harden.
past decade or so, physicists and biologists have argued that cholesterol has little effect on the hardness of membranes formed by smooth unsaturated lipids.
"it goes against our understanding of the role of cholesterol in cell membranes," Ashkar said.
" also contradicts the standard structure-characteristic relationship in self-assembled materials.
ideally, the cell membrane should maintain a semi-rigid structure: hard enough to maintain its form, but flexible enough to allow dynamic movement of signal proteins and functional domains.
about how cholesterol enhances cell membranes affects our understanding of membrane function.
the initial data didn't make much sense, but as she delved into it, Ashkar found a clear case of how soft materials showed different properties "obviously" depending on the parameters of the observation method.
she found that important signal events occur over a shorter period of time, and that added cholesterol can cause cirrhosis of the membrane.
3. "Good Cholesterol" can be used to predict the risk of heart disease and stroke for decades, and high-density lipoprotein (HDL) cholesterol has been called "good cholesterol" because it removes fat and other cholesterol molecules from arterial walls.
studies have shown that people with high HDL cholesterol levels have a lower incidence of cardiovascular disease.
, scientists at UT Southwestern University have analyzed data from more than 15,000 people to better understand the relationship between HDL cholesterol, heart attacks and strokes in different populations.
found that the amount of HDL particles, a rarely used HDL measure, more reliably predicts heart attack and stroke risk than standard HDL cholesterol indicators.
, they found that HDL levels were not significantly associated with heart attacks in blacks.
heart disease is the leading cause of death in the United States, according to the Centers for Disease Control and Prevention.
more than 12 percent of U.S. adults have high total cholesterol levels, while more than 18 percent currently think HDL cholesterol levels are low.
is used by the body to make hormones and keep cells functioning properly.
, when low-density lipoprotein (LDL) cholesterol levels are too high, cholesterol accumulates in blood vessels, forming deposits called plaques.
these plaques can eventually cause blood vessels to block, leading to a heart attack or stroke.
HDL cholesterol helps remove cholesterol from blood vessels.
but recent studies have come to new conclusions about the relationship between HDL cholesterol levels and health outcomes.
Rohatgi and his colleagues gathered information from people involved in four large national studies: the Dallas Heart Study, the Community Atherosclerosis Risk Study, the Multi-Ethnic Study of Atherosclerosis, and the Prevention of Kidney and Vascular End-stage Disease.
a total of 15,784 subjects received an average of 8 to 12 years of follow-up.
, 54 per cent were men, 22 per cent were black and the average age was 56.
, the data also include two different measures of HDL: HDL-P, which is how many HDL particles are in the blood.
the total amount of cholesterol in HDL-C, or HDL particles.
study, hdL-P had a 37 percent lower risk of heart attack and a 34 percent lower risk of stroke than those with the lowest HDL-P.
women, the association was stronger - 49 percent fewer heart attacks and 46 percent fewer strokes in women with the highest HDL-P content.
HDL-C can predict the risk of heart attack in the population as a whole and in women, it has nothing to do with stroke.
better understanding of how HDL can help predict disease and how this association changes in the population is critical to reducing the incidence of cardiovascular disease, the researchers said.
4. JEM: The King of Cancer Research New Discovery! In a study published recently in the international journal Journal of Experiment Medicine, scientists from institutions such as Cold Spring Harbor Laboratories have found that interfering with cells to store cholesterol may block the growth and progression of pancreatic cancer cells by interfering with cells to store cholesterol.
researcher David Tuveson said: 'We wanted to explain why, like many cancer cells, pancreatic cancer cells produce large amounts of cholesterol, a necessary part of the cell membrane, but the researchers were surprised to find that pancreatic cancer cells may produce much more cholesterol than they need to support their growth, which is unusual because cholesterol pathlines are the most common regulatory path path in the body's metabolism.'
Most cells produce the amount of cholesterol they need, and once cholesterol is used enough, the cells quickly shut down the synthetic path of cholesterol, but the researchers found that cancer cells convert most of the cholesterol they make into a form that can be stored in cells, so that free cholesterol does not accumulate, and the synthetic path is constantly producing free cholesterol.
cancer cells in pancreatic cancer appear to rely on this overactive cholesterol synthesis to keep moving forward, the researchers believe, perhaps because they can use the same path to produce other molecules, thanks to a type called SOAT1 (sterol O).