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Andrei Riciu

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1837

A collaboration between several universities in Spain has led to a new drug that blocks HIV replication. Researchers were able to develop a molecule that binds to the genetic material of HIV and prevent its replication. According to the study, the new molecule,  terphenyl, which is a Rev inhibitor, is able to stop the replication of the virus and to prevent the infection of other cells.

HIV is a retrovirus which means that the genetic material is composed of RNA. The genetic material contains nine genes that encode for proteins that make up the structure of the virus. Each gene has a specific role, for example, the genes tat, rev , nef , vif encode for proteins that are involved in viral replication or the ability to infect other cells. Terphenyl, the new synthetic molecule created by a team of Spanish researchers, inhibits the viral protein Rev. Terphenyl, the new drug, binds to the receptor Rev of viral RNA and blocks the interaction between the protein and its RNA receptor. This interaction is essential for the virus to leave the infected cell.

HIV

World Health Organisation ( WHO) estimated that in 2010 there were approximately 34 million individuals infected with HIV. Although HIV incidence has remained stable in recent years, however, there are certain categories  which are more affected than others such as African-Americans. It must be said, however, that although HIV incidence has remained stable, the number of people living with HIV has increased.

The emergence of resistance to antiretroviral therapies and the absence of a vaccine to combat the disease have led researchers to look for other therapeutic targets. Rev protein is considered one of these alternative targets. Now researchers want to improve the pharmacological properties oh Rev inhibitors.

Although there has not been discovered a cure for AIDS, there are several treatment regimens known as antiretroviral therapies, which keep the disease under control. There are several classes of drugs used in the management of AIDS : entry inhibitors ( or fusion inhibitors ), nucleoside and nucleotide reverse transcriptase inhibitors ( NRTIs or NtRTI ), non – nucleoside reverse transcriptase inhibitors (NNRTI ), integrase inhibitors and protease inhibitors. These drugs are used in combination therapies, of which the most common is called HAART, that is that highly active antiretroviral therapy. Studies have shown that HAART controls the disease by maintaining the function of the immune system and by preventing opportunistic infections.

 

2041

Researchers at Princess Margaret Cancer Centre have made remarkable progress in the treatment of colon cancer. It seems that disabling the gene that promotes self- renewal of tumor cells may stop not only  tumor growth but also relapses and resistance to treatment. This new approach for treating cancer had promising results and researchers hope that this will translate into humans too.

Colorectal cancer is the third most common form of cancer in men and the second in women. In terms of mortality rate, colon cancer is the fourth place after lung, stomach and liver cancer. Among the causes that lead to the development of colon cancer, diet plays an important: it seems that the consumption of red meat, fat and alcohol are among the risk factors. Also, studies have shown that an unhealthy lifestyle, obesity, lack of physical activity predispose to colon cancer. In terms of treatment, although in recent years there have been many advances in the field, however, the 5-year survival does not exceed 60 %.

cells

Principal investigator Dr. John Dick said this is the first step in applying the principles of stem cell biology to control cancer development and the first step towards a long-term cure. Dr. Dick is a Senior Scientist at University Health Network ‘s Princess Margaret Cancer Centre and McEwen Centre for Regenerative Medicine, and a Professor in the Department of Molecular Genetics, University of Toronto. It should be noted that Dr. Dick initiated the cancer stem cells field in 1994 when he identified leukemic stem cells. Also, Dr. Dick was the first to isolate stem cells from the blood in the purest form and paved the way for their clinical use.

To see that targeting stem cells can indeed provide healing, researchers replicated human colon cancer cells in mice. In this way, the researchers found that BMI -1 gene is responsible for the cycle of self- renewal, survival and proliferation; it appears that this gene is a key regulator of colon cancer stem cells. Based on these findings, the researchers created a small molecule to inhibit gene BMI -1. Dr. Dick explained by the inhibition of BMI -1 gene, stem cells were unable to self-renew which altered tumor growth. Lead author Dr. Antonija Kreso said that inhibiting this regulator of self – renewal is an effective approach to control tumor growth. She also said the study provides strong evidence that self- renewal is an important therapeutic target in cancer treatment.

2611

Prenatal exposure to alcohol alters brain development and leads to increased anxiety and poor motor skills, according to a study published in the Journal of Neuroscience. A team of researchers from the University of California, Riverside, found that offspring born from women who consumed alcohol during pregnancy have a high risk of brain abnormalities. The study results contradict popular opinion according to which alcohol consumption during pregnancy does not lead to impaired development of the offspring. According to the study, prenatal exposure to alcohol alters the connections in the neocortex, the region of the brain that is responsible for processes such as high-level thinking, vision, hearing, language, motor skills or emotions. Researchers warn that there is no safe level of drinking during pregnancy.

Kelly Huffman, assistant professor of psychology at UC Riverside and lead author of the study, explained that consuming alcohol during pregnancy can alter normal brain development. Huffman added that prenatal exposure to alcohol causes changes in the brain which lead to behavioral changes later in life. Even though the study led by researchers at the University of California have used moderate -to high- dose models, other studies have shown that even small doses of alcohol can lead to changes in key receptors in the brain. So far it has been shown that exposure to alcohol during pregnancy has negative consequences on brain development in the offspring but it a clear link between alcohol exposure and disruption of neural networks has not been established yet.

Alcohol during pregnancy

Now, Huffman says she is surprised to see that these neurobiological changes induced by alcohol exposure are quite dramatic. “We found elevated levels of anxiety, disengaged behavior, and difficulty with fine motor coordination tasks. These are the kinds of things you see in children with FASD”, she said.

It seems that alcohol leads to significant changes in intraneocortical circuits between the frontal cortex, visual and somatosensory cortex in offspring born to mothers who consumed alcohol during pregnancy. According to the study, these changes are more severe in the frontal cortex, a brain region associated with executive functions, planning, judgment, motor skills, decision-making etc.

The study also showed that children with FASD have a higher risk of having facial deformities and motor behavioral and cognitive deficits. These deficits may result later in life in mental retardation or low intelligence, poor learning skills, anxiety or depression. Children with minor forms of FASD may not develop facial deformities but still are more likely to express hyperactivity, attention problems or hyperirritability.

 

 

2371

Since the discovery of HIV in 1981, researchers have tried several strategies to eradicate this life-threatening infection. However, creating a HIV vaccine is laborious due to the complex structure of this virus. Now thanks to an EU- Funded project, researchers were able to develop a vaccine that targets gp41, an envelope protein. Gp 41 is part of the structure of the viral envelope along with gp120; because these glycoproteins help the virus to fuse with target cells of the host, there were considered one of the keypoints of a potential treatment of AIDS, especially gp120.

Now researchers have thought that if they integrated gp41 into the vaccine, they would be able to trigger an immune response that prevents penetration of HIV in human cells. Nicolas Mouze, chief scientific officer at PX’Therapeutics, one of the project partners, explained that they used an innovative approach that combined protein engineering, specific vaccine formulation and a combination of multiple routes of administration.

Alexandru Rafila, Chairman of the Romanian Society for Microbiology in Bucharest, gp41 is not an absolute novelty in the long history of the development of a vaccine against HIV. However, Rafila added that it is a meaningful approach that could result in a vaccine that would trigger an immune response. The problem is that HIV attacks not only T lymphocytes, that are essential components of the immune system but also other immune cells. It seems the latter are infected not only through gp41 but also by other mechanisms. This is why, according to Rafila, an effective vaccine would prevent infection of any other cells.

 HIV

However , there are researchers who call into question other issues such as HIV diversity and its enormous capacity to mutation. Ulrich Fruth, a vaccine development and evaluation team leader at the World Health Organisation in Geneva, Switzerland, said the idea is that a vaccine should induce antibodies T cells immune response that would attack  HIV in all of its forms.

Although this strategy aims a viable approach, Fruth believes that the success of such a vaccine is difficult to predict. He pointed out that they do not know if the project is successful and he stressed that they were more successful in trials with humans. However it seems that it is too early to draw conclusions because clinical safety studies showed a relatively low effect. In addition, Fruth pointed out that a limitation of the vaccine is that it targets only the antibodies; in order that a vaccine to be effective, it should target both T cells and antibodies, believes Fruth.

1967

Contrary to popular opinion, vitamin supplements do not alwalys bring benefits, on the contrary, these may even be harmful to our health, as shows a study conducted by researchers from the University of Oslo. Statistics show that last year 70 % of the population purchased vitamin supplements and that annually billions of dollars are spent on these products; what is concerning is that many consume these supplements in doses much higher than recommended.

Hilde Nilsen, who is heading a research group at the Biotechnology Centre, University of Oslo, pointed out that we believe that antioxidants are good for us because it protects cells from oxidative stress that can damage our genes. However, our body has an inherent ability to cope with stress. It seems that the body’s response to stress prevents DNA from eroding. Nilsen added that the delicate balance in our cells can be disrupted by vitamin supplements.

Dietary supplements

Environmental factors such as smoking, stress, ultraviolet radiation or products resulting from cellular processes can damage DNA. To see how the body defends itself from these injuries that can affect DNA, researchers at the University of Oslo made a study in which they used a microorganism called Caenorhabditis elegans (C. elegans ), a nematode, that is a worm of 1 mm long, containing 20,000 genes. Nilsen said that C. elegans is a powerful tool because they can change its hereditary properties. In other words, researchers can increase the ability to repair DNA or  can be removed it altogether. They also investigated what happens to the damaged DNA that is not repaired.

There are several types of proteins that repair damaged DNA and the most common are those that cut DNA at the damaged site and replace it with one single base. Researchers saw that aging occurs more rapidly than normal in some specimens that have the ability to repair this damage. Although most researchers believe that this is happening because lesions accumulate in DNA, which cannot synthesize the proteins needed for repair,  Nilsen is not of the same opinion. After several experiments, Nilsen noted that these lesions does not accumulate but results in less DNA. It seems that C.elegans change its metabolism and creates its own defense systems. Moreover, Nilsen showed for the first time that this response is under genetic control. Researchers call this reprogramming process. “The process has the same effect as a reduction in caloric intake, which we know helps increase the lifespan in many species”, researchers said.

It seems that the balance between oxidants and antioxidants is essential for the proper functioning of the body, but is not very clear is the echilibrium between these two. Therefore, researchers draw attention to the fact that vitamin supliments could disrupt this balance. This is why researchers recommend a healthy diet instead.

 

 

1614

The adverse effects of statins, drugs that lower blood cholesterol, might be due to interaction with other drugs taken by the patient, according to a new research published in the Journal of Clinical Lipidology. This issue is  an important issue that should be taken into account as statin discontinuation has been linked with increased cardiovascular mortality.

The researchers said that although these drug interactions with statins are known for some time, they are not adequately managed by doctors and pharmacists. It seems that the use of other drugs that interfere with statins doubles the rate of discontinuation because of muscle pain, a common adverse effect of statins. These are the conclusions reached by researchers at Oregon State University after having investigated more than 10,000 current and former statin users.

Statins ( atorvastatin, rosuvastatin, simvastatin) are drugs used in patients to prevent heart disease, atherosclerosis or after heart attack or stroke; these drugs are HMG-CoA reductase inhibitors, which means that statins lower ‘bad’ cholesterol, or LDL cholesterol. Statins represent one of the most prescribed drugs in the United States; statistics show that over 20 million Americans take these drugs. However, new guidelines extend the indications of these drugs to other diseases, so the number of people who take statins is likely to grow in the future.

Drug interactions

Matt Ito, a professor in the OSU College of Pharmacy and president of the National Lipid Association, said they know that there are many drugs that interact with statins but now there is evidence that these interactions contribute significantly to the effects effects of these drugs and that may be one of the reasons for discontinuation. He added that doctors, pharmacists and patients should be more aware of these interactions and that there are several options to optimize treatment and to prevent these side effects: trying different types of statin, avoiding drug use that does not interfere with the metabolism of statins, changing the doses etc.

Statins are usually well tolerated drugs but a recent study showed that 29 % of patients had muscle pain. It seems that this adverse effect is the main reason for discontinuation as reported 62 % of former statin users. There are several drugs that interfere with the metabolism of statins such as cardiovascular drugs, certain antibiotics, drugs for cancer, etc. Patients who have adverse effects due to treatment with statins should not discontinue the treatment but discuss these issues with their doctors or pharmacists to see what are the options.

 

 

1953

With the help of a new technology, called RNA interference, researchers at the National Institutes of Health have revealed new genes that could be used as therapeutic targets for the treatment of Parkinson’s disease. The new study provides new information not only about Parkinson’s disease but also about other diseases caused by mitochondrial dysfunction. Richard Youle, Ph.D., an investigator at the National Institutes of Neurological Disorders and Stroke (NINDS ), and the leader of the study  said they discovered a network of genes that control dysfunctional mitochondria and which could therapeutic targets in the treatment of Parkinson’s disease.

Mitochondria are essential organelles in cell metabolism as mitocondria generate the main energy source of the cell: adenosine triphosphate.  Genes that control the proper functioning of the mitochondria are involved in many neurological diseases such as Parkinson’s disease, Charcot Marie Tooth disease or ataxia. Some cases of Parkinson’s disease are related to mutations in genes encoding for parkin, a protein that removes damaged mitochondria. Mutations in the gene coding for parkin alters cellular metabolism and leads to accumulation of damaged mitochondria in the cell.

genes

 

The team of researchers from the National Institutes of Health used iRNA  to silence over 22,000 genes in the human body. The researchers wanted to see the effect of silencing these genes on parkin function and how does this affects mitochondria. For the study, researchers used iRNA to see which genes help parkin to tag mitochondria. It seems that there are at least four genes involved in parkin tag: TOMM7, HSPAI1L, BAG4 and SIAH3; the first two, when inhibited, block parkin tag, while the last two, when switched off, increase parkin tag. The levels of certain proteins in cells are controlled by a process called ubiquitination, and studies have shown that there are many genes that are responsible for ubiquitination or that encode for proteins involved in mitochondrial metabolism.

Researchers have used the induced pluripotent stem cell technology to create nerve cells from  skin cells and then tested one of these genes in the human nerve cells. It seems that blocking TOMM7  inhibits parkin tag. Story Landis, Ph.D., director of the NINDS, said that the study shows that the latest high- throughput genetic technologies can quickly reveal fundamental mechanisms behind the disease. These results have prompted the researchers to think that these genes could be therapeutic targets in the treatment of certain neurological diseases. “The identification of these helper genes provides the research community with new information that may improve our understanding of Parkinson’s disease and other neurological disorders” researchers said.

1988

A study led by scientists at the Research Institute at Nationwide Children’s Hospital uncovers why a certain bacterium that causes ear and respiratory infections eludes the immune system and causes chronic infections. The study, led by Kevin M. Mason, PhD, and Sheryl S. Justice, PhD, principal investigator in the Center for Microbial pathogenesis,  reveals new data on nontypeable Haemophilus influenzae ( NTHI ), the bacteria responsible for most  ear and throat infections.

Haemophilus influenzae is part of a family consisting of several strains, among which the most common is the type b, or Hib. In the past, Haemophilus influenzae was the leading cause of bacterial meningitis in children under 5 years, but with the introduction of Hib vaccine in 1985 , the incidence of this disease decreased significantly. But now NTHI is the leading cause of invasive infections in both adults and children.

 

ear checkup 

NTHI, should be noted, is part of commensal bacterial flora of the oropharynx, a microenvironment rich in heme -iron, a compound essential for the survival of the bacterium. NTHI creates problems when migrates to other regions such as the lungs or middle ear, where heme -iron is sequestered by immune system response. This is why researchers wanted to find out why NTHI can cause problems precisely where its development is not favorable microenvironment.

Researchers have learned how this bacterium manages to cause the immune system to work in his favor. It seems that with the first signs of  infection, there is a process called nutritional immunity, that is the immune response blocks the access to nutrients bacteria. The initial immune response triggers other events to fight off the infection such as the release of compounds that lead to inflammation (to isolate bacteria ) and migration of white blood cells to the site of infection, etc.

In an experiment that mimicked the immune response to NTHI infection in the middle ear, researchers observed that the serum  that contained compounds to kill bacteria, white blood cells and other agents, also  included heme -iron. When NTHI was re- exposed to heme -iron, suffered several changes, it became more elongated and divided more slowly. Because leukocytes were trained to target shorter rapidly dividing cells, NTHI infection went on.

This adaptation that is responsible for bacterial resistance to antibiotics prompted researchers to look for new ways to combat these infections. One method would be to use an inhibitor to block a critical pathway in the survival of bacteria. “If we could design a small molecule inhibitor that would look like heme-iron but would actually clog up a key metabolic pathway in bacteria, we may be able to get around the problem of antibiotic resistance,” suggests Dr. Mason.

2330

An experiment conducted by a team of Japanese researchers from the Keio University School of Medicine, offers new hope for patients with spinal cord injuries. They managed to obtain motor functional recovery after injecting neural stem / progenitor cells (NS / PCs ) in mice. It was known for some time that transplantation of neural stem / progenitor cells (NS / PCs ) promotes functional recovery in spinal cord injury, but it was not very clear what is the optimal transplantation site. Therefore, researchers made an experiment in which they injected NS / PCs in four groups of mice in several sites : at the lesion epicenter, caudal and rostral sites; the control group received phosphate buffered saline. It should be noted that all mice included in the study received contusive spinal cord injury at the T10 level.

Dr. Masaya Nakamura of the Department of Orthopedic Surgery at the Keio University School of Medicine, emphasized that it is critical to determine the optimal site for transplanting NS / PCs designed to treat spinal cord injury. Previous studies conducted by the same team showed that NS / PCs injected intravenously or intrathecally in non – injury sites, did not engraft at the lesion site in sufficient numbers;  the researchers observed that instead these NS / PCs were trapped in the lungs or kidney. In this way they concluded that the optimal outcome for transplantation of NS / PCs can be obtained by intralesional application. To determine how effective is intralesional injection, researchers conducted another study on laboratory mice with spinal cord injury. They  injected NS / PCs taken from transgenic mice for Venus and luciferase fusion protein, a method that allowed the researchers to track the cells after transplantation by bioluminescence imaging ( BLI ).

spine

Dr. Nakamura explained that wild-type mice received a spinal cord injury at T10 and that low and high doses of NS / PCs taken from fetal transgenic mice were administered to four groups of mice;  the fifth group received phosphate buffered saline. Researchers reported that all four groups of mice had functional motor recovery while mice in the control group did not. The researchers also mentioned that in all four groups, the photon counts from BLI transplant were similar. In other words, the survival of stem cells was uniform when it was transplanted more than a certain threshold number of cells. However, it seems that there is a difference between rostral and caudal (RC ) sites and lesion epicenter (E ) because brain -derived neurotropic factor expression was higher in RC. “This may mean that the microenvironments of the E and RC sites are similarly able to support NS/PCs transplanted during the sub-acute phase of SCI,” researchers said.

2128

A new study by researchers at Brigham and Women ‘s Hospital ( BWH ) and published in the journal Circulation, shows that men who suffer from insomnia have a higher risk of mortality. Insomnia is the most common of sleep diseases and statistics show that this disorder affects a third of the U.S. population. Dr. Yanping Li, a research fellow in the Channing Division of Network Medicine at BWH and lead author of the paper, said that insomnia is a common health problem particularly in elderly adults, but that the link between this sleep disorder and its impact on health is unclear. Dr Li has stated that their study showed that among men who experienced symptoms of insomnia there is a moderate risk of death related to cardiovascular issues.

The study led by researchers at Brigham and Women ‘s Hospital shows that difficulty in falling asleep and restless sleep are associated both with a higher risk of mortality, in particular with cardiovascular disease -related mortality. They reached this conclusion they conducted a study that included more than 23,000 men who reported insomnia for more than 6 years. From 2004 to 2010, of the 23,000 cases investigated, the researchers found 2,025 deaths. Taking into account factors related to lifestyle, age or other chronic conditions, researchers found that men who experienced difficulty in falling asleep or who had a restless sleep, had an 55% and 32 % increased risk of mortality related to cardiovascular issues during the 6 years of follow -up.

Insomnia

 

Xiang Gao, MD, PhD, a researcher in the Channing Division of Network Medicine at BWH and Harvard School of Public Health and senior author of this study,  said that we know that sleep is important for cardiovascular health and many studies have shown that poor sleep is associated with increased cardiovascular risk. He added that the study shows that sleep quality not only has an impact on disease risk, but also on our longevity. “While further research is necessary to confirm these findings, there is overwhelming evidence that practicing good sleep hygiene and prioritizing sufficient and restful sleep is an often overlooked but important modifiable risk factor in overall health”, Dr. Gao pointed out.

There are many factors that can lead to insomnia: situational factors (noise , light intensity), psychological factors (stress, depression, anxiety ), medical factors ( sleep apnea, nocturnal asthma, reflux disease, etc. );  insomnia can be caused by various stimulants such as caffeine or nicotine. Regarding the treatment of insomnia, it can be non-pharmacological, such as behavioral therapy or relaxation therapy, or pharmacological. However, it is best to identify and treat the cause of insomnia first.