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A protein that normally deposits mineralized calcium in tooth enamel may also be responsible for calcium in the back of the eye

A protein that normally deposits mineralized calcium in tooth enamel may also be responsible for calcium deposits in the back of the eye in people with dry age-related macular degeneration (AMD), according to a study from researchers at the National Eye Institute (NEI). This protein, amelotin, may turn out to be a therapeutic target for the blinding disease. The findings were published in the journal Translational Research. NEI is part of the National Institutes of Health. "Using a simple cell culture model of retinal pigment epithelial cells, we were able to show that amelotin gets turned on by a certain kind of stress and causes formation of a particular kind of calcium deposit also seen in bones and teeth. When we looked in human donor eyes with dry AMD, we saw the same thing," said Graeme Wistow, Ph.D., chief of the NEI Section on Molecular Structure and Functional Genomics, and senior author of the study. There are two forms of AMD -- wet and dry. While there are treatments that can slow the progression of wet AMD, there are currently no treatments for dry AMD, also called geographic atrophy. In dry AMD, deposits of cholesterol, lipids, proteins, and minerals accumulate at the back of the eye. Some of these deposits are called soft drusen and have a specific composition, different from deposits found in wet AMD. Drusen form under the retinal pigment epithelium (RPE), a layer of cells that transports nutrients from the blood vessels below to support the light-sensing photoreceptors of the retina above them. As the drusen develop, the RPE and eventually the photoreceptors die, leading to blindness. The photoreceptors cannot grow back, so the blindness is permanent. Recently, researchers found a calcium-containing mineral compound called hydroxyapatite (HAP) in dry AMD deposits. HAP is a key component of tooth enamel and bone. Small balls of HAP filled with cholesterol, called spherules, were found only in drusen from people with dry AMD, and not in those with wet AMD or without AMD. In this study, Wistow's team discovered that if they starved RPE cells grown in transwells, a type of cell culture system, for 9 days, the cells began to deposit HAP. They determined that the protein amelotin, encoded by the gene AMTN, is strongly upregulated after extended starvation and is responsible for the mineralization of HAP in their cell culture model. Blocking this pathway in their RPE cell line also blocked the production of these drusen-like deposits. To verify that their cell culture model was accurately representing dry AMD, the researchers examined human cadaver eyes with dry AMD, wet AMD, or without AMD. They found HAP and amelotin only in the eyes with dry AMD, and not in the other eyes. While amelotin was found sometimes in areas of dry AMD without drusen, it was primarily present in soft drusen areas with large deposits of HAP. "Prior to this study, nobody really knew how the hydroxyapatite was accumulating in the dry AMD drusen," said Dinusha Rajapakse, Ph.D., the first author of the study. "Finding this tooth-specific protein in the eye, this protein that's linked to hydroxyapatite deposition -- that was really unexpected." Why RPE cells in dry AMD begin depositing these HAP spherules is unclear, but Wistow thinks it may be a protective mechanism gone awry. It's possible, he says, that these protein, lipid and mineral deposits may help damaged RPE cells block blood vessels from growing into the retina, a problem that is one of the key features of wet AMD. But when the mineral deposits get too extensive, they may also block nutrient flow to the RPE and photoreceptors, leading to retinal cell death. "Mechanistically, amelotin looks like a key player for the formation of these very specific hydroxyapatite spherules. That's what it does in the teeth, and here it is in the back of the eye. Conceptually, you could see coming up with drugs that specifically block the function of amelotin in eye, and this might delay the progression of the disease. But we won't know until we try it," said Wistow. Good animal models for testing dry AMD therapeutics are urgently needed. Based on the findings from this study, Wistow and his team are creating a new mouse model for the disease. Additionally, Wistow believes his cell culture model, which mimics features of dry AMD, could potentially be useful for high throughput drug screening to find molecules that slow or prevent the development of soft drusen. Story Source: Materials provided by NIH/National Eye Institute. Note: Content may be edited for style and length.

9th July, 2020

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Could this plaque identifying toothpaste prevent a heart attack or stroke?

For decades, researchers have suggested a link between oral health and inflammatory diseases affecting the entire body -- in particular, heart attacks and strokes. Inflammation is intimately involved in the pathogenesis of atherosclerosis and is accurately measured by high sensitivity C-reactive protein (hs-CRP), a sensitive marker for future risks of heart attacks and strokes. Researchers from Florida Atlantic University's Schmidt College of Medicine, Marshfield Clinic Research Institute, and the University of Wisconsin School of Medicine and Public Health, collaborated on a randomized trial titled, "Correlation between Oral Health and Systemic Inflammation" (COHESION), to further explore whether Plaque HD®, a plaque identifying toothpaste, reduces hs-CRP. Results of the randomized pilot trial, published online ahead of print in the American Journal of Medicine, showed that Plaque HD® produced a statistically significant reduction in hs-CRP among those with elevations at baseline. Plaque HD® is the first toothpaste that identifies plaque so that it can be removed with directed brushing. In addition, the product's proprietary formulation contains unique combinations and concentrations of cleaning agents that weaken the core of the plaque structure to help the subject visualize and more effectively remove the plaque. In this trial, all randomized subjects were given the same brushing protocol and received a 30-day supply of toothpaste containing either Plaque HD® or an identical non-plaque identifying placebo toothpaste. To assess hs-CRP, levels were measured by Quest Diagnostics using an enzyme-linked immunosorbent assay. "The current findings are similar to those from our previous pilot trial," said Charles H. Hennekens, M.D., Dr.P.H., senior author, first Sir Richard Doll Professor, and senior academic advisor in FAU's Schmidt College of Medicine. "Whether this plaque-identifying toothpaste decreases heart attacks or strokes requires a large-scale randomized trial of sufficient size and duration. These results provide a stronger rationale to conduct such trials. If positive, the results of these trials would have significant potential clinical and public health implications." Based on these findings, Hennekens and colleagues at FAU and the University of Wisconsin School of Medicine and Public Health are drafting an investigator-initiated research grant proposal to the National Institutes of Health (NIH). Their proposed randomized trial will test whether Plaque HD® reduces the progression of atherosclerosis in the coronary and carotid arteries, for which systemic inflammation is an important precursor. A report from the United States Centers for Disease Control and Prevention found that 47.2 percent of American adults aged 30 years and older have some form of periodontal disease, a pathological inflammatory condition of the gums and tissues surrounding the teeth. Periodontal disease increases with age affecting more than 70 percent of adults 65 years and older. Prior research has suggested that periodontal disease may be connected to a variety of other diseases, including heart disease and stroke and other inflammatory diseases such as rheumatoid arthritis. Inflammation throughout the body may be a crucial link between periodontal and other systemic diseases. To read from source, click on the link below : https://www.sciencedaily.com/releases/2020/02/200224100554.htm

9th July, 2020

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Health Benefits of Flavonoids

What are Flavonoids? Flavonoids are polyphenolic plant pigments widely present in vegetables, fruits, herbs and spices. Lesser known than vitamin C and E, these are a group of antioxidants that are lately receiving a lot of attention for their health benefits. The bioavailability of flavonoids is relatively low for two reasons. One, their absorption from the digestive tract is usually limited. Secondly, these are very quickly eliminated from the body. The most bioavailable group of flavonoids is the isoflavones that contain the soy flavonoid called genistein. Health Benefits of Flavonoids Flavonoids are especially known for their antioxidant activities, which play a significant role in cardiovascular health and in the prevention of cancer. Other than fighting free radicals, they are also known for their antihistamine, antimicrobial, memory enhancing and even mood-boosting properties. Flavonoids May have Potential for Killing Cancer Cells - A study from the University of Illinois showed that celery, artichokes, and herbs, especially Mexican oregano, contain flavonoids that killed human pancreatic cancer cells under lab conditions. The flavonoids act by inhibiting an important enzyme. However, the research team said that the trick seemed to be in using the flavonoids as a pre-treatment instead of using them and the chemotherapeutic drug simultaneously, since ‘flavonoids can act as antioxidants and taking antioxidant supplements on the same day as chemotherapeutic drugs may negate the effect of those drugs’. Flavonoids have Cardiovascular Benefits - A review study published in the American Journal of Clinical Nutrition confirmed earlier researches on benefits of chocolate flavonoids on cardiovascular health. The researchers found that chocolate or cocoa reduced blood pressure and had significant effects on LDL and HDL cholesterol. Health Benefits of Flavonoids: Blood Pressure Flavonoids are Beneficial in Controlling Diabetes - The study also found that insulin resistance was improved by chocolate or cocoa due to significant reductions in serum insulin. Isoflavones may Ease Menopausal Symptoms - Soybean isoflavones have been found to reduce hot flash frequency in perimenopausal and postmenopausal women, according to a study by researchers at National Institute of Health and Nutrition, Tokyo, Japan. Isoflavones may Reduce the Risk of Osteoporosis - Scientists have also found that soy isoflavones may prevent postmenopausal osteoporosis and improve bone strength, thus decreasing the risk of fracture in menopausal women by significantly increased bone mineral density. Proanthocyanidins Reduce the Destruction of Collagen - Grape seed proanthocyanidin extract (GSPE) acting as an antioxidant has a therapeutic effect on collagen-induced arthritis, say the researchers at The Rheumatism Research Center, The Catholic University of Korea, Seoul. They experimented on lab animals and found that GSPE significantly reduced hydrogen peroxide production that destroyed collagen. The researchers also suggested that GSPE may be beneficial for the treatment of chronic autoimmune inflammation, which is commonly observed in rheumatoid arthritis. Proanthocyanidins may Prevent Gum Disease - The anti-inflammatory activity of cranberry proanthocyanidins can effectively inhibit the invasiveness of the gum disease-causing bacteria. Canadian researchers are of the opinion that proanthocyanidins can not only prevent gum diseases but may be used to treat the disease as well. Flavonoids Improve Cognition in Older Adults - The flavonoid antioxidants, especially anthocyanidins, have shown to improve cognition in experimental studies. Greater intakes of blueberries and strawberries were associated with slower rates of cognitive decline, according to Harvard researchers. They also pointed out that ‘berry intake appears to delay cognitive aging by up to 2.5 years’. Incidentally, flavonoids also reduce the slowing of body movements, fatigue, irritability, and depression, all associated with free radical damage. Health Benefits of Flavonoids: Cognitive Decline Flavonoid Food Sources All fruits and vegetables contain one or the other flavonoids to a certain degree. 1. Catechins 2. Theaflavins 3. Proanthocyanidins 1. Teas (particularly green and white), chocolate, grapes, berries, apples 2. Teas (particularly black and oolong) 3. Chocolate, apples, berries, red grapes, red wine Another classification of flavonoid foods is based on their flavonoid content. High flavonoid content (50mg / 100g food) - examples: onion, kale, green bean, broccoli, celery, cranberry, orange juice Medium flavonoid content (1 to 5mg / 100g food) - examples: tomato, bell pepper, strawberry, broad bean, apple, grape, red wine, tea, tomato juice Low flavonoid content (under 1mg /100g food) - examples: cabbage, carrot, mushroom, pea, spinach, peach, white wine, coffee Interestingly, there is no evidence of side effects associated with dietary intake of flavonoids. The reason could be attributed to their low bioavailability, that is, poor absorption and quick elimination. However, flavonoids in the supplement form do have side effects, and sometimes severe ones. For example, they can cause nausea, headache, or tingling of the extremities in some people when taken in doses of 1000mg per day. Similarly, a study showed that tea extracts supplement can cause liver toxicity in some cancer patients. It is best to avoid flavonoid supplements during pregnancy and lactation because their safety has not been established in these conditions. News Courtesy: MD India

8th July, 2020

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Complexity of human tooth enamel revealed at atomic level

Scientists used a combination of advanced microscopy and chemical detection techniques to uncover the structural makeup of human tooth enamel at unprecedented atomic resolution, revealing lattice patterns and unexpected irregularities. The findings could lead to a better understanding of how tooth decay develops and might be prevented. The research was supported in part by the National Institute of Dental and Craniofacial Research (NIDCR) at the National Institutes of Health. The findings appear in Nature on July 1, 2020. "This work provides much more detailed information about the atomic makeup of enamel than we previously knew," says Jason Wan, Ph.D., a program officer at NIDCR. "These findings can broaden our thinking and approach to strengthening teeth against mechanical forces, as well as repairing damage due to erosion and decay." Your teeth are remarkably resilient, despite enduring the stress and strain of biting, chewing, and eating for a lifetime. Enamel—the hardest substance in the human body—is largely responsible for this endurance. Its high mineral content gives it strength. Enamel forms the outer covering of teeth and helps prevent tooth decay, or caries. Tooth decay is one of the most common chronic diseases, affecting up to 90% of children and the vast majority of adults worldwide, according to the World Health Organization. Left untreated, tooth decay can lead to painful abscesses, bone infection, and bone loss. Tooth decay starts when excess acid in the mouth erodes the enamel covering. Scientists have long sought a more complete picture of enamel's chemical and mechanical properties at the atomic level to better understand—and potentially prevent or reverse—enamel loss. To survey enamel at the tiniest scales, researchers use microscopy methods such as scanning transmission electron microscopy (STEM), which directs a beam of electrons through a material to map its atomic makeup. Impurities such as magnesium show up as dark distortions (indicated by white arrows) in the atomic lattice of human enamel crystallites. Credit: Paul Smeets, Northwestern University & Berit Goodge, Cornell University STEM studies have shown that at the nanoscale, enamel comprises tightly bunched oblong crystals that are about 1,000 times smaller in width than a human hair. These tiny crystallites are made mostly of a calcium- and phosphate-based mineral called hydroxylapatite. STEM studies coupled with chemical detection techniques had hinted at the presence of much smaller amounts of other chemical elements, but enamel's vulnerability to damage from high-energy electron beams prevented a more thorough analysis at the necessary level of resolution. To define these minor elements, a team of scientists at Northwestern University, Evanston, Illinois, used an imaging tool called atom probe tomography. By successively removing layers of atoms from a sample, the technique provides a more refined, atom-by-atom view of a substance. The Northwestern group was among the first to use atom probe tomography to probe biological materials, including components of teeth. "Earlier studies revealed the bulk composition of enamel, which is like knowing the overall makeup of a city in terms of its population," says senior author Derk Joester, Ph.D., a professor of materials science and engineering at Northwestern. "But it doesn't tell you how things operate at the local scale in a city block or a single house. Atom probe tomography gave us that more detailed view." The scientists used atom probe tomography and advanced STEM techniques in a complementary fashion to overcome prior technical limitations. The Northwestern researchers worked with imaging experts led by Lena Kourkoutis, Ph.D., an associate professor of applied and engineering physics and director of electron microscopy at Cornell University's national materials science user facility, PARADIM, in Ithaca, New York. At Cornell, the scientists coupled an ultra-fast chemical detector with STEM at very low temperatures to minimize enamel damage and gather more detailed chemical data. The complementary approaches enabled the team to piece together information at multiple levels of resolution to get a more complete view of the chemical and structural features of enamel crystallites. The results showed that the crystallites were made of a continuous uniform lattice of hydroxylapatite atoms. However, the lattice structure appeared to be sprinkled with dark distortions, especially at the innermost core of the crystallites. A closer look at the core revealed that these defects were caused by the presence of minor elements that previous studies had hinted at. One such element was magnesium, which was highly concentrated in two distinct layers in the core. The central region was also rich in sodium, fluorine, and carbonate. Flanking the core was a "shell" with much lower concentrations of these elements. In three views of the same sample of enamel crystallites, atom probe tomography reveals the distributions of three minor elements, with each colored dot representing a single atom. These maps show that magnesium is present in two distinct layers in the core, and fluorine and sodium are heavily concentrated in the areas between crystallites, known as the intergranular phase. Credit: Karen DeRocher, Northwestern University "We assumed that human crystallites would be similar in composition to rodent enamel, which is widely used by researchers to understand human enamel," says co-first author Paul Smeets, Ph.D., a research associate in the Northwestern Atomic and Nanoscale Characterization Experimental Center. "But that was not the case—human enamel is much more chemically complex than we thought." The scientists suspected that the irregularities introduced by magnesium layers give rise to areas of strain in the crystallite. Computer modeling supported their hunch, predicting higher stresses in the core than in the shell. "Stress may sound bad, but in material science it can be useful, and we think it may make enamel stronger overall," says co-first author Karen DeRocher, a graduate student in Joester's lab. "On the other hand, those stresses are predicted to make the core more soluble," which might lead to erosion of enamel. Indeed, when the researchers exposed crystallites to acid—similar to what happens in the mouth—the core showed more erosion than the shell. Further modeling and experiments will be necessary to confirm these results, as well as to explore the idea that stress introduced by chemical impurities may fortify enamel and make it more resistant to fracture. The group also plans to continue using these approaches to learn more about how acid affects enamel. "This new information will enable model-based simulation of enamel degradation that wasn't possible before, helping us better understand how caries develops," says DeRocher. The findings could lead to new approaches to toughen enamel and prevent or reverse cavity formation.

6th July, 2020

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Oropharyngeal secretions may help reduce false negative COVID-19 test results

As the global battle to understand and eliminate the coronavirus continues, a new study published in the Journal of Dental Research demonstrates that testing of oropharyngeal secretions (OS) may reduce the number of false negative results from nasal swab testing of patients who have seemingly recovered from the disease. In the study, led by Jingzhi Ma, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Department of Stomatology, Wuhan, China, a small number of patients that had tested negative through nasopharyngeal swabs were found to be positive through the testing of oropharyngeal secretions. The first prospective study of its kind included 75 ready-for-discharge COVID-19 patients who tested negative using two consecutive nucleic acid amplification testing (NAAT) of viral samples retrieved with nasopharyngeal swabs (NPS). Because of detection of potential false-negatives in that cohort, NAAT results of paired OS and NPS samples collected from 50 additional COVID-19 recruits during their recovery stage were used in a second prospective study to compare the diagnostic values of the two viral RNA sampling methods. Oropharyngeal secretions obtained from 2 of the 75 subjects in the first study yielded positive results for SARS-CoV-2 nucleic acid. In the second study, OS samples were significantly more sensitive for detection of the virus that NPS samples and missed only 14% of positive cases compared with 59% for the NPS samples. Sampling of OS is a simple procedure that can be performed in any quarantine setting and minimizes contact between healthcare workers and patients, thereby reducing the risk of virus transmission. "The NPS test has a risk of sending home more patients who still have the infection while the OS test will make such errors in fewer patients. Although OS sampling improves the accuracy of SARS-CoV-2 nucleic acid testing, it must be emphasized that this conclusion is based on a very small sample size," stated Ma. To read from the source, click on the link below : https://medicalxpress.com/news/2020-07-oropharyngeal-secretions-false-negative-covid-.html

6th July, 2020

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Tongue Microbiome Could Help Early Detection of Pancreatic Cancer

Tongue surface coat microbiome is altered in pancreatic cancer patients, reveals a new study from China. There are differences in the bacterial population on the surface coating of the tongue of pancreatic cancer patients compared to normal healthy individuals. This difference could help in developing rapid diagnostic tests for the early detection of pancreatic cancer. The microbiome consists of the sum total of all the microorganisms that live in a particular niché within or on the surface of the body. Although, changes in the microbiome have been observed in pancreatic cancer patients in various other tissues of the body, this is the first time it has been reported from the surface coating of the tongue. This could open up new avenues for the development of fast and convenient diagnostic tests for the early detection of pancreatic cancer. This new study has been published in the Journal of Oral Microbiology, a publication of Taylor & Francis, UK. ‘Microbiome of the tongue surface coating is altered in pancreatic cancer patients. The change in the degree of colonization of bacteria could help in developing rapid diagnostic tests for early detection and prevention of progression of cancer.’ The study was led by Dr. Lanjuan Li, MD, who is a Professor of Infectious Diseases and Director, State Key Laboratory for Infectious Diseases, Zhejiang University, Hangzhou, China. Background of the Study The incidence of pancreatic cancer is approximately 10,000 people annually in the UK. Of these, less than one percent survive for more the ten years. Therefore, an early diagnosis of the disease is extremely important for the prompt institution of treatment, before cancer spreads to other parts of the body i.e. undergoes metastasis. However, early detection is difficult, as the pancreas is located deep within the body and doesn't show symptoms until the cancer is in an advanced stage. As a result, by the time patients seek medical help, cancer has already metastasized. Ongoing research for the early detection of pancreatic cancer focuses on looking for biological changes that could help in identifying early signs of pancreatic cancer. This would enable the development of screening tools that could detect cancer at an early stage. In this regard, the gut microbiome has been found to be a very promising target. Interestingly, previous studies have shown significant changes in the microbiome of the saliva, intestine and stool samples in pancreatic cancer patients compared to healthy controls. Key Features of the Study The main features of the study are highlighted below: This is the first study to characterize the tongue surface coat microbiome of pancreatic cancer patients and compare with that of healthy individuals Participants included 30 end-stage pancreatic cancer patients and 25 healthy individuals In the pancreatic cancer cases, the tumor was located in the 'head' region of the pancreas Age of the participants ranged between 45 and 65 years Participants did not have any other disease or oral health issues Participants did not take any antibiotics or other drugs in the preceding three months of the study Microbiome diversity of the tongue surface coat was characterized by using state-of-the-art gene sequencing technology Key Findings of the Study There was a stark difference in the microbiome of the tongue surface coating of pancreatic cancer patients, compared to healthy individuals The degree of colonization by four types of bacteria was studied. In pancreatic cancer cases, the following were noted: Colonization by Haemophilus and Porphyromonas was low Colonization by Leptotrichia and Fusobacterium was high The degree of colonization by the above four bacteria could differentiate between pancreatic cancer patients and healthy individuals With reference to the study findings, Li said: "Although further confirmatory studies are needed, our results add to the growing evidence of an association between disruptions to the microbiome and pancreatic cancer." To read from the source, click on the link below: https://www.medindia.net/news/healthinfocus/tongue-microbiome-could-help-early-detection-of-pancreatic-cancer-185473-1.htm

3rd July, 2020

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