Human Kidney Computational Model

Researchers at the University of Waterloo in Canada developed a new computational model of the human kidney to replace previous computational models that are based on rodent kidneys.

This computational model enables researchers to better learn about the functions of the kidney, including how the organ regulates the body’s salt, potassium, and acid content and enables the study of disease mechanisms and medications that affect the kidney, such as diabetes, without harmful effects to humans or animals.

Understanding the function of the human kidney has been vastly improved by using computational studies to evaluate renal function at the single nephron level.

One major benefits of having a computational model of the human kidney is the ability to provide a platform for simulations to predict the effects of a new drug toxicity, or to explain the underlying mechanisms of observed effects.

The computational model can mimic the effects of the drug to see if it is harmful for the kidney, and if so, it provides insight into the site of damage.

Layton AT, Layton HE. A computational model of epithelial solute and water transport along a human nephron. PLoS Computational Biology. 2019;15. doi: 10.1371/journal.pcbi.1006108

Reducing Risk for Chronic Disease

According to a study funded by the National Cancer Institute (NIH), those eating vegan diets are less likely to develop chronic diseases, compared with other dietary groups.

Researchers analyzed the diets of those following vegan, lacto-ovo-vegetarian, semi-vegetarian, pesco-vegetarian, and non-vegetarian eating patterns and tracked several health biomarkers. Based on those biomarkers, the vegan group had the lowest risk for cancer, heart disease, and hypertension, compared with the other groups. The vegan group also had higher levels of omega-3 fatty acids and higher serum levels of carotenoids and isoflavones associated with lower inflammation. Vegans consumed the most fruits, vegetables, whole grains, and legumes and had the highest intakes of beta-carotene and fiber and the lowest intakes of saturated fatty acids.

The vegan group was the only group to be in a healthy weight range, while all other groups were overweight, on average. These findings offer more insight into the relationship between diet-related biomarkers and disease and support vegan diets as a healthful approach to disease prevention.

Miles FL, Lloren JIC, Haddad E, et al. Plasma, urine, and adipose tissue biomarkers of dietary intake differ between vegetarian and non-vegetarian diet groups in the Adventist Health Study-2. J Nutr. Published online February 15, 2019

Protecting Your Brain

A new study published in the Journal of Alzheimer’s Disease found that
eating more mushrooms could help to protect your brain from cognitive impairment.

Researchers found those people who had the highest intake of
edible mushrooms also had the lowest risk of mild cognitive impairment (MCI). The researchers at the National University of Singapore explored the possibility that eating more mushrooms could protect cognitive
abilities later in life. Researchers studied 663 people aged 60 for over 6
years focusing on the most common mushrooms eaten in Singaporean
cuisine, which included: golden, oyster, shitake, white button, dried or canned button mushrooms. They counted ¾ of a cup of cooked mushrooms as a single portion, and measured the participants’ cognitive abilities
throughout the study, using a variety of techniques, including: the
Wechsler Adult Intelligence Scale (to assess IQ), interviews and a series of physical and psychological tests. Weight and height were measured, as well as blood pressure, hand grip and walking speed. The study
participants were also assessed for cognition, depression and anxiety,
and rated on a dementia symptom scale. Astonishingly, the researchers
found that eating two or more servings of mushrooms per week was
sufficient to reduce the risk of mild cognitive impairment by 50 percent. They believe that a compound known as ergothioneine (ET), a potent
anti-inflammatory and antioxidant compound found in mushrooms, may be responsible for the impressive results. Mushrooms are among the
best sources of this powerful brain protective compound. ET may not be the only factor as mushrooms contain a diversity of healing compounds
known as hericenones, erinacines, scabronines and dictyophorines, all of which could contribute to the growth of bran cells. While it is not clear which of the compounds, or whether all of the compounds, are to thank
for mushrooms’ memory protective properties, it is easy to start
benefiting from them by simply eating more mushrooms in your diet

Addiction now defined as brain disorder

Addiction now defined as brain disorder, not behavior issue.

Decades of research convinced American Society of Addiction Medicine to change definition

Addiction is a chronic brain disorder and not simply a behavior problem involving alcohol, drugs, gambling or sex, experts contend in a new definition of addiction, one that is not solely related to problematic substance abuse.

The American Society of Addiction Medicine (ASAM) just released this new definition of addiction after a four-year process involving more than 80 experts.

“At its core, addiction isn’t just a social problem or a moral problem or a criminal problem. It’s a brain problem whose behaviors manifest in all these other areas,” said Dr. Michael Miller, past president of ASAM who oversaw the development of the new definition. “Many

Behaviors driven by addiction are real problems and sometimes criminal acts. But the disease is about brains, not drugs. It’s about underlying neurology, not outward actions.”

The new definition also describes addiction as a primary disease, meaning that it’s not the result of other causes, such as emotional or psychiatric disorders. And like cardiovascular disease and diabetes, addiction is recognized as a chronic disease; so it must be treated, managed and monitored over a person’s lifetime, the researchers say.

Two decades of advancements in neuroscience convinced ASAM officials that addiction should be redefined by what’s going on in the brain. For instance, research has shown that addiction affects the brain’s reward circuitry, such that memories of previous experiences with food, sex, alcohol and other drugs trigger cravings and more addictive behaviors. Brain circuitry that governs impulse control and judgment is also altered in the brains of addicts, resulting in the nonsensical pursuit of “rewards,” such as alcohol and other drugs.

A long-standing debate has roiled over whether addicts have a choice over their behaviors, said Dr. Raju Hajela, former president of the Canadian Society of Addiction Medicine and chair of the ASAM committee on addiction’s new definition.

“The disease creates distortions in thinking, feelings and perceptions, which drive people to behave in ways that are not understandable to others around them,” Hajela said in a statement. “Simply put, addiction is not a choice.  Addictive behaviors are a manifestation of the disease, not a cause.”

Even so, Hajela pointed out, choice does play a role in getting help.

“Because there is no pill which alone can cure addiction, choosing recovery over unhealthy behaviors is necessary,” Hajela said.

This “choosing recovery” is akin to people with heart disease who may not choose the underlying genetic causes of their heart problems but do need to choose to eat healthier or begin exercising, in addition to medical or surgical interventions, the researchers said.

“So, we have to stop moralizing, blaming, controlling or smirking at the person with the disease of addiction, and start creating opportunities for individuals and families to get help and providing assistance in choosing proper treatment,” Miller said.

Low Carbohydrate Diets Increase Risk Heart for Disorder

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Important Note: This study references complex carbohydrates

Low-carbohydrate diets increase the risk for atrial fibrillation (AFib), a common disorder of heart rhythm, according to a poster presented at the American College of Cardiology’s 68th Annual Scientific Session.

Researchers tracked daily carbohydrate intake in 14,000 diet records from the Atherosclerosis Risk in Communities (ARIC) study and monitored incidences of heart arrhythmias.

Those who consumed the least amount of carbohydrate increased the chance of developing AFib by 18 percent, compared with those who consumed the most carbohydrate.

 AFib is associated with a five-fold increased risk for stroke and may lead to heart failure.

Carbohydrate restriction lowers intake of grains, fruits, and vegetables linked to reduced inflammation and may increase consumption of high-fat, high-protein foods associated with oxidative stress.

Zhuang X. U-shaped relationship between carbohydrate intake proportion and incident atrial fibrillation. Poster presented at: 68th American College of Cardiology’s Annual Scientific Session. March 16-18, 2019; New Orleans, LA. ffffffffff

Aid in Alzheimer’s Study

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.

Xu J, Patassini S, Rustogi N, et al. Regional protein expression in human
Alzheimer’s brain correlates with disease severity.
Communications Biology. 2019;2. doi:10.1038/s42003-018-0254-9.

Placenta-on-a-chip Research

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.

A New Model to Study Brain Tumors

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.

Heinrich MA, Bansal R, Lammers T, Zhang YS, Schiffelers RM, Prakash J. 3D-Bioprinted mini-brain: A glioblastoma model to study cellular interactions and therapeutics. Advanced Materials. 2019. https://doi.org/10.1002/adma.201806590

Hope of Restored Vision

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.

3D-Bio-printed Tumor to Help Identify New Therapeutics

3D-Bioprinted Tumor to Help Identify New Therapeutics
University of Minnesota researchers developed 3D-bioprinted
vascularized tumor tissue to study the molecular mechanisms of tumor
progression and metastasis, and identify therapeutic agents and screen
anticancer drugs.

This in vitro model is completely comprised of human cells, making it
translatable to human anatomy and physiology. Studying the effects of
drugs with human cells at this level makes the results more predictive of what will happen in the body. This model can even use the patients’ own tumor cells leading to advancements in treatments targeted to specific tumor types.  

Vascularized tumor models are created to mimic key steps of cancer
invasion, intravasation, and angiogenesis. This 3D-bioprinted tumor
model can provide valuable understandings into the clinical
translatability of potential treatments since it provides simplified
chemical environments, making it more convenient to define
molecular mechanisms.

Researchers initially focused on lung cancer and melanoma. They are
planning to incorporate more cell types, like immune system cells, as well as cell therapies, and study those interactions. 

DMeng F, Meyer CM, Joung D, et al. 3D bioprinted in vitro metastatic models via reconstruction of tumor microenvironments. Advanced Materials. 2019. https://doi.org/10.1002/adma.201806899