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Home > Press > Nano-lipid particles from edible ginger could improve drug delivery for colon cancer, study finds Abstract: Edible ginger-derived nano-lipids created from a specific population of ginger nanoparticles show promise for effectively targeting and delivering chemotherapeutic drugs used to treat colon cancer, according to a study by researchers at the Institute for Biomedical Sciences at Georgia State University, the Atlanta Veterans Affairs Medical Center and Wenzhou Medical University and Southwest University in China. Colorectal cancer is the third most common cancer among men and women in the United States, and the second-leading cause of cancer-related deaths among men and women worldwide. The incidence of colorectal cancer has increased over the last few years, with about one million new cases diagnosed annually. Non-targeted chemotherapy is the most common therapeutic strategy available for colon cancer patients, but this treatment method is unable to distinguish between cancerous and healthy cells, leading to poor therapeutic effects on tumor cells and severe toxic side effects on healthy cells. Enabling chemotherapeutic drugs to target cancer cells would be a major development in the treatment of colon cancer. In this study, the researchers isolated a specific nanoparticle population from edible ginger (GDNP 2) and reassembled their lipids, naturally occurring molecules that include fats, to form ginger-derived nano-lipids, also known as nanovectors. To achieve accurate targeting of tumor tissues, the researchers modified the nanovectors with folic acid to create FA-modified nanovectors (FA nanovectors). Folic acid shows high-affinity binding to the folate receptors that are highly expressed on many tumors and almost undetectable on non-tumor cells. The FA nanovectors were tested as a delivery platform for doxorubicin, a chemotherapeutic drug used to treat colon cancer. The researchers found that doxorubicin was efficiently loaded into the FA nanovectors, and the FA nanovectors were efficiently taken up by colon cancer cells, exhibited excellent biocompatibility and successfully inhibited tumor growth. Compared to a commercially available option for delivering doxorubicin, the FA nanovectors released the drug more rapidly in an acidic pH that resembled the tumor environment, suggesting this delivery strategy could decrease the severe side effects of doxorubicin. These findings were published in the journal Molecular Therapy. "Our results show that FA nanovectors made of edible ginger-derived lipids could shift the current paradigm of drug delivery away from artificially synthesized nanoparticles toward the use of nature-derived nanovectors from edible plants," said Dr. Didier Merlin, a professor in the Institute for Biomedical Sciences at Georgia State and a Research Career Scientist at the VA Medical Center. "Because they are nontoxic and can be produced on a large scale, FA nanovectors derived from edible plants could represent one of the safest targeted therapeutic delivery platforms." ### Dr. Mingzhen Zhang of the Institute for Biomedical Sciences at Georgia State is the first author of the study. Co-authors of the study include Dr. Emilie Viennois, Dr. Zhan Zhang and Moon Kwon Han of the Institute for Biomedical Sciences at Georgia State; Dr. Bo Xiao of the Institute for Biomedical Sciences at Georgia State and Southwest University in Chonqing, China; and Dr. Changlong Xu of the Institute for Biomedical Sciences at Georgia State and Wenzhou Medical University in Wenzhou, China. The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, the Department of Veterans Affairs and the Crohn's & Colitis Foundation of America. For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

News Article | April 8, 2016
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​Nanoparticles designed to block a cell-surface molecule that plays a key role in inflammation could be a safe treatment for inflammatory bowel disease (IBD), according to researchers in the Institute for Biomedical Sciences at Georgia State University and Southwest University in China. The scientists developed nanoparticles, or microscopic particles, to reduce the expression of CD98, a glycoprotein that promotes inflammation. Their findings are published in the journal Colloids and Surfaces B: Biointerfaces. “Our results suggest this nanoparticle could potentially be used as an efficient therapeutic treatment for inflammation,” says Didier Merlin, professor in the Institute for Biomedical Sciences at Georgia State and researcher at the Atlanta Veterans Affairs Medical Center. “We targeted CD98 because we determined in a previous study that CD98 is highly over-expressed in activated immune cells involved in IBD.” In the U.S., as many as 1.3 million people suffer from IBD, which includes ulcerative colitis and Crohn’s disease, conditions with chronic or recurring abnormal response to the body’s immune system and inflammation of the gastrointestinal tract. IBD gets worse over time and causes severe gastrointestinal symptoms, such as persistent diarrhea, cramping abdominal pain, fever, rectal bleeding, loss of appetite, and weight loss. Surgery is required when medication can no longer control the symptoms, and patients also have an increased risk of colon cancer, according to the Centers for Disease Control and Prevention. This study suggests the development of nanotherapeutic strategies could be an alternative to currently available drugs, which are limited by serious side effects, in treating inflammatory conditions such as IBD. In the study, researchers formed the nanoparticles by combining CD98 siRNA, small interfering RNA that inhibit CD98 gene expression in macrophages (immune cells involved in IBD), with urocanic acid-modified chitosan (UAC). Chitosan is a polysaccharide obtained from the hard outer skeleton of shellfish. When introduced to macrophages, the nanoparticles had an anti-inflammatory effect on these immune cells. Researchers found the nanoparticles had a desirable particle size and no apparent toxicity against macrophages and colon epithelial cells. Cell studies showed nanoparticles with a weight ratio of 60:1 (UAC:siCD98) had the best anti-inflammatory capacity. Co-authors of the study include Emilie Viennois from the Institute for Biomedical Sciences at Georgia State and Atlanta Veterans Affairs Medical Center; Panpan Ma of Southwest University in Chongqing, China; and Bo Xiao from the Institute for Biomedical Sciences at Georgia State and Southwest University in Chongqing, China. The study was funded by the Department of Veterans Affairs, the National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases, and the National Natural Science Foundation of China. Source: University of Georgia

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A new Northwestern Medicine study has pinpointed thousands of genetic pathways an internal body clock takes to dictate how and when our pancreas must produce insulin and control blood sugar, findings that could eventually lead to new therapies for children and adults with diabetes. The body’s circadian clocks coordinate behaviors like eating and sleeping, as well as physiological activity like metabolism, with the Earth’s 24-hour light-dark cycle. There’s a master clock in the brain, as well as peripheral clocks located in individual organs. When genetics, environment or behavior disrupt the synchrony of these clocks, metabolic disorders can develop. In a previous publication in Nature, Northwestern Medicine investigators showed that a circadian clock in the pancreas is essential for regulating insulin secretion and balancing blood sugar levels in mice. The scientists demonstrated that knocking out clock genes led to obesity and type 2 diabetes, but they still had much to learn if they wanted to manipulate clock action to treat the conditions. “We knew that the pancreas didn’t work if we removed these clock genes, but we didn’t know how the genes were affecting the normal function of the pancreas,” said principal investigator Dr. Joe Bass, chief of endocrinology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine physician. Clock genes are responsible for producing transcription factors, special proteins that help tell a cell how to function. In the new study, published Nov. 6 in Science, Bass’s laboratory revealed thousands of genes in the pancreas that the clock’s transcription factors control in rhythm with the planet’s daily rotation from light to dark. “We established a new gene map that shows how the entire repertoire of factors produced in the pancreas maintain and anticipate daily changes in the external environment,” Bass said. “These factors are all tied to the rotation of the Earth -- to the timekeeping mechanism that has evolved to control when we sleep, wake up, eat and store nutrients each day.” Bass’s team focused on cells in the pancreas called beta cells, which secrete insulin into the blood stream to help the body absorb glucose -- sugar -- to use for energy. Using genome-wide sequencing technology on beta cells with both intact and disrupted clock gene function, the scientists were able to lay out the map of transcription factors and genes. In ongoing research, Bass’s group continues to study how the body’s circadian clocks interact and how their rhythm is thrown off -- not just in diabetes, but also during the normal aging process and from day-to-day conditions like jetlag, stress or dietary changes. “This study reinforces the idea that clocks operating in cells are fundamental to health,” Bass said. “They represent an important untapped target for improving the functions of cells in the pancreas.” Bass is also the Charles F. Kettering Professorship of Medicine at Feinberg. Other Northwestern authors include Dr. Grant Barish, Mark Perelis, Biliana Marcheva, Kathryn Ramsey, Clara Bien Peek, Hee-kyung Hong, Matthew Schipma, Dr. Akihiko Taguchi, Dr. Wenyu Huang, Chiaki Omura and Amanda Allred. This study was supported by National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH National Institute on Aging , the Chicago Biomedical Consortium , Juvenile Diabetes Research Foundation , University of Chicago Diabetes Research and Training Center 5; NIDDK T32 ; National Heart, Lung, and Blood Institute T32and Defense Advanced Research Projects Agency.

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Human bodies don’t contain 10 times as many bacteria as human cells, new calculations suggest. A “standard man” weighing 70 kilograms has roughly the same number of bacteria and human cells in his body, researchers report online January 6 at bioRxiv.org. This average guy would be composed of about 40 trillion bacteria and 30 trillion human cells, calculate researchers at the Weizmann Institute of Science in Rehovot, Israel, and the Hospital for Sick Children in Toronto. That’s a ratio of 1.3 bacteria to every one human cell. That estimate could be off by as much as 25 percent, with the average number of bacteria ranging from 30 trillion to 50 trillion. Among individual people, the bacterial count could vary as much as 52 percent, say Ron Sender, Shai Fuchs and Ron Milo. With a fudge factor of 10 trillion to 20 trillion bacteria, the number of microbes may pretty well match the number of human cells in the body, which also varies somewhat. “Indeed, the numbers are similar enough that each defecation event may flip the ratio to favor human cells over bacteria,” the researchers write. Scientists who study the microbiome, the collection of microorganisms that live in and on the human body, have peppered research papers with an estimate that bacteria outnumber human cells 10-to-1 or even 100-to-1. In recent years, those estimates have come into question, with the American Academy of Microbiology suggesting in 2013 that the real figure is probably closer to three bacterial cells for each human cell. An average adult human man’s body contains about 30 trillion human cells, most of them red blood cells. Pictured is a breakdown of the most common cell types. Judah Rosner, a molecular biologist at the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Md., called the 10-to-1 ratio a “fake fact” in a 2014 issue of Microbe. It probably wormed its way into scientific literature because it sounds good, Rosner says. “Everybody likes a nice, round number. And it had such impact. It was good PR.” But Rosner and others wondered where the number had come from in the first place. Sender and Milo at the Weizmann Institute and Fuchs now at the Hospital for Sick Children traced the figure to a single, back-of-the-envelope calculation in a 1972 paper. The researchers combed scientific literature to come up with their own estimates of bacterial and human cell numbers. Plenty of cocktail-party fodder is buried in the results. For instance, the team finds that red blood cells are the most numerous cells in the body, accounting for 84 percent of cells in the body by number. By weight, muscle and fat are the heavy hitters, making up 75 percent of cell mass. But those cells tend to be big and represent only about 0.2 percent of the human body cell number. As expected, most of the bacteria in the body — about 39 trillion — live in the colon. Women tend to have smaller blood volume than men, so their bacteria-to-human cell ratio may be about 30 percent higher than that of men, the researchers calculate. Growing children probably fall within the range of bacteria-to-human cell ratios of adult men. Obesity doesn’t change the ratio much, the team calculates. These estimates haven’t been checked by other scientists yet, but microbiome researchers say they appreciate the effort to examine the ratio. “Anytime people can add more precision it’s good,” says microbiologist Martin Blaser of New York University School of Medicine. The researchers didn’t do any experiments, and Blaser says others should begin measuring bacterial and human cell numbers to get an even more accurate number. Other researchers point out that the new paper’s calculations considered only bacteria, while viruses, fungi, archaea and other microbes are also part of the human microbiome. Viruses vastly outnumber bacteria (SN: 1/11/14, p.18) and could skew the microbe-to-human cell ratio upwards, says Julie Segre, a geneticist at the National Human Genome Research Institute in Bethesda, Md., and a leader of the human skin microbiome project. Most microbiome research has focused on how relative amounts of bacteria change between health and disease, but scientists don’t yet know whether the absolute amount of bacteria is also important, says microbiologist Ran Blekhman at the University of Minnesota, Twin Cities. The reduced ratio in no way diminishes the effect bacteria have on human health, commenters told Science News. Most said it doesn’t matter what the real number is, just that it’s right. Besides, “one-to-one is pretty impressive,” Rosner says. “There’s as much of them as there is of us.” Editor’s note: This story was updated January 13, 2016, to correct a rounding error from the paper regarding the share of human cells that comes from fat and muscle.

Gagniuc P.,University of Bucharest | Ionescu-Tirgoviste C.,National Institute of Diabetes
BMC Genomics | Year: 2013

Background: Gene promoters have guided evolution processes for millions of years. It seems that they were the main engine responsible for the integration of different mutations favorable for the environmental conditions. In cooperation with different transcription factors and other biochemical components, these regulatory regions dictate the synthesis frequency of RNA molecules. Predominantly in the last decade, it has become clear that nuclear organization impacts upon gene regulation. To fully understand the connections between Homo sapiens chromosomes and their gene promoters, we analyzed 1200 promoter sequences using our Kappa Index of Coincidence method.Results: In order to measure the structural similarity of gene promoters, we used two-dimensional image-based patterns obtained through Kappa Index of Coincidence (Kappa IC) and (C+G)% values. The center of weight of each promoter pattern indicated a structure similarity between promoters of each chromosome. Furthermore, the proximity of chromosomes seems to be in accordance to the structural similarity of their gene promoters. The arrangement of chromosomes according to Kappa IC values of promoters, shows a striking symmetry between the chromosome length and the structure of promoters located on them. High Kappa IC and (C+G)% values of gene promoters were also directly associated with the most frequent genetic diseases. Taking into consideration these observations, a general hypothesis for the evolutionary dynamics of the genome has been proposed. In this hypothesis, heterochromatin and euchromatin domains exchange DNA sequences according to a difference in the rate of Slipped Strand Mispairing and point mutations.Conclusions: In this paper we showed that gene promoters appear to be specific to each chromosome. Furthermore, the proximity between chromosomes seems to be in accordance to the structural similarity of their gene promoters. Our findings are based on comprehensive data from Transcriptional Regulatory Element Database and a new computer model whose core is using Kappa index of coincidence. © 2013 Gagniuc and Ionescu-Tirgoviste; licensee BioMed Central Ltd. Source

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