New Insight into the Progression of Chronic Pain

Researchers in Brazil (D’Or Institute for Research & Education), in conjunction with scientists at L’Oréal, successfully differentiated human induced pluripotent stem cells (hiPSC) into peripheral sensory neurons—or the neurons that innervate our arms, legs, fingers, and toes—in the presence of skin cells. The cells were responsive to pain-causing irritants, such as capsaicin, resiniferatoxin, anandamide, bradykinin, potassium solution, and hydrogen peroxide.

This study co-cultured hiPSC cells with skin cells to provide insight into how sensory neurons play a role in skin renewal and the detection of painful stimuli. The implications of their findings are useful in studying chronic pain, predicting causes of neuroinflammation, and potentially individualized disease modeling.

The researchers of this study expressed that this technique can be applied to patient-derived hiPSCs to aid in the development of personalized in vitro disease models.

Animals used to mimic pain in humans do not depict human neural physiology, and cannot capture the progression of a disease that may vary from person to person.

 

Guimaraes MZP, De Vecchi R, Vitoria G, et al. Generation of iPSC-derived human peripheral sensory neurons releasing substance P elicited by TRPV1 agonists. Front Mol Neurosci. 2018;11:277. doi: 10.3389/fnmol.2018.00277

Redefining Research: Growth of Human Mini-Brains

Researchers discovered how to incorporate oligodendrocytes, an essential brain cell type, into the growth of human “miniature brains-in-a-dish” derived from stem cells. These new brain organoids can model human brain structures more accurately because the oligodendrocytes allow for the formation of myelin—the insulating coating that protect nerves—and are critical for faster relay of nerve signals.

The researchers used the organoids to test drugs that enhance myelin production and showed that the testing platform is an effective tool for predicting the safety and efficacy of such drugs. In addition, they generated organoids from patients with a rare fatal myelin genetic disorder called Pelizaeus-Merzbacher disease that recapitulate features of the disease and can be used to test potential therapies.

The incorporation of oligodendrocytes allows human brain diseases to be modeled more accurately in a dish for research, especially for diseases that involve problems with myelination, such as multiple sclerosis.

 

Madhavan M, Nevin ZS, Shick HE, et. al. Induction of myelinating oligodendrocytes in human cortical spheroids. Nature Methods. 2018. doi: 10.1038/s41592-018-0081-4

Omega-3 Supplements Do Not Protect Against Heart Disease

According to a review published in Cochrane Database of Systematic Reviews, researchers reviewed 79 studies that compared consumption of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA) with cardiovascular health. Long-chain fatty acids from fish oil supplements did not protect against all-cause mortality and did not reduce the risk for cardiovascular events.

Results showed increased consumption of ALAs from plant-foods provided a protective effect against coronary heart disease, arrhythmia, and other cardiovascular events. The authors note that previous recommendations for fish oil supplementation derived from biased research.

 

Abdelhamid AS, Brown TJ, Brainard JS, et al. Omega 3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. Published online July 18, 2018.

Artificial Intelligence Outperforms Doctors in Diagnosing Skin Cancer

Researchers developed a new artificial intelligence (AI) tool known as a deep learning convolutional neural network (CNN), and found it is able to diagnose skin cancer (specifically melanoma) more accurately than a group of 58 international dermatologists with varying levels of expertise. The tool was created using Google’s AI technology and was trained using 100,000 skin images.

The CNN improved the doctors’ accuracy of diagnosis for skin cancers from a sensitivity of 86.6 to 95 percent (i.e., the doctors missed fewer true cancerous moles) and from a specificity of 71.3 to 82.5 percent (i.e., the doctors misdiagnosed fewer noncancerous moles as cancerous).

Therefore, the tool can prevent fewer cancer patients from being misdiagnosed as normal early on in their disease progression, as well as, prevent patients without cancer from undergoing unnecessary diagnostic procedures and treatments.

 

Haenssle HA, Fink C, Schneiderbauer R, et al. Man against machine: diagnostic performance of a deep learning convolutional neural network for dermoscopic melanoma recognition in comparison to 58 dermatologists. Ann Oncol. 2018.https://doi.org/10.1093/annonc/mdy166.

 

Computational Tool Provides 3-D Views of Molecular Processes

New Computational Tool Provides 3-D Views of Molecular Processes Affecting Human Metabolism

Researchers  created a novel virtual resource called Recon3D to provide biologists with 3-D perspectives of spatially linked genes, proteins, and metabolites for analyzing molecular processes affecting human metabolism.

Recon3D is currently available online through two databases: BiGG Models and the Virtual Metabolic Human database.

The tool can offer insights into the mechanisms of action for disease-related mutations and reveal how genes, proteins, and metabolic reactions respond to drugs. It has been used to analyze human sequencing data to map mutation hotspots in 3D as well as to show that drugs with different molecular structures can exert similar metabolic responses.

This first resource of its kind provides the most comprehensive human metabolic map to date, and accounts for 17 percent of the known functional genes in the human genome.

It will help break research ground on the molecular mechanisms of human metabolism and offer a new human-based approach towards understanding diseases affected by metabolism.

Reference Link: https://www.nature.com/articles/nbt.407

 

 

 

Human-Centered Research Framework

Adopting human-focused research framework may help produce results more relevant to human physiology and overcome translational barriers in diabetes research.

Using animal models for researching type 2 diabetes mellitus (T2DM) impedes scientific breakthroughs about the disease origins and treatment options.

Researchers recently proposed a human-centered research framework to study the biology of sugar metabolism in humans from molecules to population studies by utilizing novel human-based research technologies such as organ-on-chips and computer simulations.

This human-relevant framework, which incorporates in human cells and tissues and computer modeling technologies, holds great promise to advance the current prevention, diagnosis, and treatment of T2DM in humans.

 

Ali Z, Chandrasekera PC, Pippin JP. Animal research for type 2 diabetes mellitus: limited translation to clinical benefit and the path forward. Altern Lab Anim. Mar 2018. Retrieved from http://www.atla.org.uk/animal-research-for-type-2-diabetes-mellitus-its-…

 

Red Meat Increases Risk for Colon Cancer

According to a study published online in the International Journal of Cancer, a diet in red meat increases risk for colon cancer in women.

Researchers compared cancer incidence rates for dietary patterns centered on red meat, fish, poultry, or no meat in 32,147 women. Those who consumed red meat were more likely to develop distal colon cancer than those who consumed no red meat.

The authors note that higher intakes of dietary fiber, vitamins, and minerals associated with meat-free diets may protect against cancer.

Rada‐Fernandez de Jauregui D, Evans CEL, Jones P, Greenwood DC, Hancock N, Cade JE. Common dietary patterns and risk of cancers of the colon and rectum: Analysis from the United Kingdom Women’s Cohort Study (UKWCS). Intl J Cancer. Published online April 1, 2018.

 

Grilled Meat Increases Risk for Hypertension

Researchers compared meat consumed after high-temperature cooking methods and tracked hypertension incidence rates from more than 100,000 disease-free participants.

Increased consumption of red meat, fish, and chicken prepared on an open-flame and cooked longer at higher temperatures increased the risk for high blood pressure.

 

Liu G. Meat cooking methods and risk of hypertension: results from three prospective cohort studies. Abstract presented at EPI|LIFESTYLE 2018 Scientific Sessions; March 20-23, 2018; New Orleans, LA

Plant-Based Diets Good For Heart Health

According to a new review published in Progress in Cardiovascular Diseases, vegetarian and vegan diets are associated with a healthier cardiovascular profile.

Physicians Committee researchers looked at multiple clinical trials and observational studies and found strong and consistent evidence that plant-based dietary patterns may prevent, and reverse atherosclerosis and decrease other markers of CVD risk, including blood pressure, blood lipids, and weight.

Kahleova H, Levin S, Barnard ND. Vegetarian dietary patterns and cardiovascular disease. Prog Cardiovasc Dis. Published online May 29, 2018.

 

Model for Human Intestine

Researchers at the Wyss Institute developed a model of the human intestine containing microchannels populated by different human cells to form tissues, which can be used to study the gut microbiome, the immune system, and chronic conditions like cancer.

The Intestine Chip offers an innovative approach to making research more human-relevant and has the capability to model an individual’s gut, which will lead to advances in precision medicine. The chip’s microchannels can be populated with human cells from multiple donors, offering a human-relevant platform for disease modeling and drug development. The ability for the chip to model an individual’s gut presents new ways to advance precision medicine, which focuses on identifying treatments and preventions that are more effective for individuals based on their genetics and environmental and lifestyle factors. Precision medicine is revising the “one-size-fits-all” approach to health care.

The Intestine Chip may be useful as a research tool for many applications, including studies of metabolism, disease modeling and progression, drug absorption, and more. Until now, in vitro models had limited ability to study enteropathies. The Intestine Chip offers the ability to replicate conditions such as colorectal cancer, cystic fibrosis, and celiac disease. The Intestine Chip model also has the capability to study new therapeutic targets, test new treatments, and repurpose existing pharmaceuticals.

Bein A, Shin W, Jalili-Firoozinezhad S, et al. Microfluidic organ-on-a-chip models of human intestine. Cellular and Molecular Gastroenterology and Hepatology. 2018;5:659-668. https://doi.org/10.1016/j.jcmgh.2017.12.010