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Donated Human Brains Aid Alzheimer’s Study

Using donated human brains, researchers from the Universities of Manchester, Bristol, Liverpool, and Auckland studied the differences of protein expression between healthy human brains and those with Alzheimer’s disease to produce the largest dataset of its type ever, and the data is freely available online for any scientist to use.

Alzheimer’s is a progressive form of dementia that interferes with memory, thinking, and behavior. Alzheimer’s currently affects 36 million people worldwide with no disease-modifying treatment available. Alzheimer’s follows distinctive development patterns that are not replicated in animals, making it vital to study human brains.

Scientists used the donated brains to map more than 5,825 distinctive proteins across six regions of the brains and showed that areas of the brain involved in functional changes in Alzheimer’s showed the greatest changes in proteins. Thus, there is a predictive gradient of protein changes that is associated with disease severity.

This study allowed researchers to observe how Alzheimer’s progresses in greater detail and identify new molecular and protein changes that were previous not known to be associated with the disease. By studying thousands of individual proteins, this research has generated a detailed molecular map of changes in the brain throughout the progression of Alzheimer’s. Making this information open source will help others continue deepening our understanding of Alzheimer’s and identify targets that can be used to develop therapeutics.

Caffeine Transfer from Mother to Fetus Studied with Placenta-on-a-Chip

Researchers at Iowa State University have used “placenta-on-a-chip” technology, to see if, and how much, caffeine can cross from mother to baby.

In the human body, the placenta feeds oxygen and nutrients from the mother into the fetus through the umbilical cord. A thin barrier separates the mother’s bloodstream from the fetus’, however, many chemicals and substances can cross that barrier.

Iowa State researchers designed a placenta-on-a-chip, using human umbilical vein endothelial cells and trophoblasts cells, which work like the placental barrier, and tested how well compounds could cross it.

To date, most human placenta drug testing methods use animals, which seldom replicate to human responses.

The placenta-on-a-chip platform enables researchers to further study the pharmacokinetics of different drugs across the placental barrier, and also to examine the safety of drugs administered to pregnant women.

Caffeine transport across the placental barrier was studied because caffeine is a foreign substance to the body and is widely consumed on a daily basis. Scientific literature on the amount of caffeine safe for consumption during pregnancy is conflicting, further investigation on caffeine transport across the placenta barrier is warranted.

Pemathilaka RL, Caplin JD, Aykar SS, Montazami R, Hasemi NN. Placenta-on-a-chip: In vitro study of caffeine transport across placental barrier using liquid chromatography mass spectrometry. Global Challenges. 2019. https://doi.org/10.1002/gch2.201800112.

3D-Bioprinted Mini-Brain: A New Model to Study Brain Tumors

Scientists at the University of Twente in the Netherlands created a 3D-bioprinted mini model of the brain consisting of glioblastoma cells, which are the site of a very aggressive type of brain tumor, to study the interactions between immune cells and to test drugs that target this interaction.

This newly developed 3D model allows researchers to study the tumor cell characteristics, and how they interact with human immune cells, which help the tumor rather than attacking it.

Researchers reported this model shows results that are aligned with actual patient data, demonstrating it to be far more beneficial than existing lab models.

This 3D-bioprinted model provided evidence for how therapeutics can inhibit the interaction between tumor cells resulting in reduced tumor growth, and increased susceptibility to chemotherapy. Scientists anticipate that this tumor model can help improve the understanding of tumor biology and aid in the testing of novel cancer treatments. The promising results of this model show that it can likely be used to study other types of tumors as well.

Donated Human Eye Tissue Offers Hope of Restored Vision

Doctors at the University of Edinburgh carried out the first-ever randomized clinical trial for limbal stem cell deficiency, a condition that causes blindness, using stem cells from deceased human donors to create tissue that was transplanted into patients with the disease.

Researchers isolated stem cells from the donated corneas and grew the cells into healthy tissues that were transplanted into half of the participating study patients. The patients that received the stem cell treatment showed significant improvements in vision and repair of the outermost layer of the eyes.

Donated human tissues and organs assist in the discovery of cures and treatments to ensure better health for all. Organ and tissue donors have the opportunity to make a significant contribution to scientific advancement, and in this case, provide others with the gift of sight. Using human stem cells in clinical trials sheds a new light on the causes of sight disorders and allows for the discovery of new treatments.

The findings from this study show the potential for promising stem cell eye surgery and improvements in eye repair. This study has motivated researchers to pursue a better understanding of how stem cells facilitate tissue repair for diseases that are extremely hard to treat, and hopefully develop new techniques to restore vision among patients with limbal stem cell deficiency

Campbell JD, Ahmad S, Agrawal A, et al. Allogeneic ex vivo expanded corneal epithelial stem cells transplantation: A randomized controlled clinical trial. Stem Cells Transl Med. 2019.

Human Metabolism on a Computer: B

Bio-Transformer is a freely available computational tool that can predict and identify chemical, drug, pesticide, and food compound metabolites in humans and the environment.

Humans encounter a large number of chemicals in the course of one day. Provided our bodies are working optimally and under the right circumstances, we can tolerate many chemicals without adverse effects due to a function of metabolism.

Key: Human metabolism is complex and in many respects different from that of other species. Using the BioTransformer tool will help to more accurately predict how humans metabolize chemicals, rather than relying on incorrect information from animal tests.

The highlight of this tool is that it is open access and demonstrated to be similar to, if not better than, comparable commercial software. In addition, it includes small molecule metabolism by environmental microbes, which currently has not been explored in software tools of its kind. Open access tools and publications encourage scientific sharing that will lead to breakthroughs in computational modeling and machine learning in the field of molecular metabolism for safety assessment.

Djoumbou-Feunang Y, Fiamoncini J, Gil-de-la-Fuente A, et al. BioTransformer: a comprehensive computational tool for small molecule metabolism prediction and metabolite identification.  J Cheminform. 2019;11:2. https://doi.org/10.1186/s13321-018-0324-5

Plant-Based Diets Reduce Risk for Gallstones

Researchers followed 4,839 participants and tracked diet, cholesterol levels, and gallstone incidence rates. Women who consumed a nonvegetarian diet had an increased risk for gallstones, compared with women who consumed a vegetarian diet.

Women with hypercholesterolemia had almost 4 times the risk for gallstones, compared with vegetarian women who had normal cholesterol levels.

Vegetarian diets lower cholesterol through increased fiber intake and may protect against other risk factors including insulin resistance and obesity.

Chang CM, Chiu THT, Chang CC, Lin MN, Lin CL. Plant-based diet, cholesterol, and risk of gallstone disease: a prospective study. Nutrients. 2019;11:335-349.

Vegetarian diets reduce the risk for gallstone disease, according to research published in Nutrients.

Alzheimer’s disease is the most common neurodegenerative disorder, affecting 47 million people worldwide, with 5.7 million cases in the United States alone. Sporadic Alzheimer’s disease accounts for more than 90 percent of all Alzheimer’s cases. This form disproportionally affects people without a family history of the disease and is believed to be caused by a variety of environmental and genetic risk factors.

Geneticists at Harvard Medical School created a new model-in-a-dish of sporadic Alzheimer’s disease using neural cells derived from sporadic Alzheimer’s disease and induced pluripotent stem cells. This model signifies the first time researchers have ever been able to identify the same molecular irregularities across several lines of sporadic Alzheimer’s disease and provides greater understanding into early molecular alterations that may lead to the disease.

This new cell model is an important step forward in narrowing down the factors involved in sporadic Alzheimer’s disease and toward the development of potential therapies that stop or reverse the disease progression.

This human-based in vitro model identified changes in neural stem cells during early development. During analysis, researchers observed unusually high activity in genes related to neuron differentiation in the sporadic Alzheimer’s disease cells, suggesting that brain cells derived from patients with neurodegeneration develop faster, not slower, than cells derived from non-Alzheimer’s patients. Researchers can now use this new model to study the impact on this more rapid maturation of on neuronal stem cells, thus opening a new scientific direction into the early development of Alzheimer’s disease.