Quantum dot technology to advance molecular cell imaging

Researchers from the University of Illinois at Urbana-Champaign bioengineering team and Mayo Clinic have engineered a new type of molecular probe that can measure and count RNA in cells and tissue without organic dyes. The probe is based on the conventional fluorescence in situ hybridization (FISH) technique, but it relies on compact quantum dots to illuminate molecules and diseased cells rather than fluorescent dyes. This research is published in Nature Communications.

Quantum dots illuminate the locations of individual mRNA as red dots in the cytoplasm of a single HeLa cell. The blue region is the nucleus.  Credit: University of Illinois at Urbana-Champaign Department of Bioengineering

Over the last 50 years, fluorescence in situ hybridization technique has evolved into a multi-billion-dollar industry because it effectively images and counts DNA and RNA in single cells. However, fluorescence in situ hybridization technique has its limitations due to the delicate nature of the dyes. For example, the dyes rapidly deteriorate and are not very good at imaging in three dimensions. In addition, conventional fluorescence in situ hybridization technique can only read out a couple of RNA or DNA sequences at a time. Using quantum dots, however, can illuminate the locations of individual mRNA as red dots in the cytoplasm of a single HeLa cell.

The team created unique quantum dots that are made of a zinc, selenium, cadmium, and mercury alloy and are coated with polymers. “The core of the dot dictates the wavelength of emission, and the shell dictates how much light will be given off,” said Smith, who is also affiliated with the Micro + Nanotechnology Lab, Carle Illinois College of Medicine, and Department of Materials Science and Engineering at the University of Illinois.

These dots can emit color independent of the size of the particle, which is not the case for conventional quantum dots. The dots are also small enough (7 nanometers) to fit on a probe that can maneuver between proteins and DNA in a cell, making them more comparable in size to the dyes used in conventional FISH probes.

In experiments with HeLa cells and prostate cancer cells, the researchers found that dye-based FISH cell counts declined rapidly in minutes. The quantum dot-based FISH method provided long-term luminescence to allow counting of RNA for more than 10 minutes, making it possible to acquire 3D cell imaging.

Citation: Liu, Yang, Phuong Le, Sung Jun Lim, Liang Ma, Suresh Sarkar, Zhiyuan Han, Stephen J. Murphy, Farhad Kosari, George Vasmatzis, John C. Cheville, and Andrew M. Smith. “Enhanced mRNA FISH with Compact Quantum Dots.” Nature Communications 9, no. 1 (2018). doi:10.1038/s41467-018-06740-x.

Improvements in optical mammography to advance breast cancer diagnostics

Researchers from Politecnico di Milano, Italy report improvements in the design of optical mammography used in diagnosis and monitoring of breast cancer.  They report increase sensitivity by a thousandfold.This research is presented at Biomedical Optics meeting 2018.

Schematic diagram of new and improved optical mammography device.
Credit: Edoardo Ferocino

Optical mammography uses infrared light and is used in conjunction with x-rays. It is optimal in cases needing repeated imaging to prevent high amounts of radiation associated with the regular procedure. Optical mammography can be used to measure blood volume, oxygenation, lipid, water and collagen content for a suspicious area identified through standard X-ray imaging. However, there are limitations to using optical mammography, which includes poor spatial resolution.

New improvements include using eight channel silicon photomultipliers (SiPMs) and multichannel time-to-digital converter instead of two photomultiplier tubes (PMTs) in existing optical mammography instruments. These changes eliminate the pre-scan step that was required to avoid damage to the photomultiplier tubes. In addition to increased sensitivity, the new instrument is both more robust and cheaper.

The investigators in Milan are working with a larger consortium on a project known as SOLUS, “Smart Optical and Ultrasound Diagnostics of Breast Cancer.” This project is funded by the European Union through the Horizon 2020 Research and Innovation Program and aims to combine optical imaging methods with ultrasound to improve specificity in the diagnosis of breast cancer.

Adapted from press release by the Optical Society.

A new approach to create targeted nanovesicles for cancer treatment

Researchers have used autologous immune cells from the mouse to create nanovesicles to be used in the delivery of drugs to tumors. This technique helped them to create a sufficient number of nanovesicles inexpensively to be used as drug delivery system.

This image shows ligands-grafted extracellular vesicles as drug delivery vehicles.
Credit: Xin Zou 

Cells naturally release nanovesicles to carry chemical messages between cells. To create targeted nanovesicles, ligands (short pieces of protein) need to be attached to the nanovesicle wall so they can recognize tumor cells. This is done by incorporating DNA into cells and collecting extracellular nanovesicles from cell culture supernatant. However, the yield of nanovesicles is poor using above process. Researchers now developed a new approach by chemically grafting lipid tagged ligands to the cell membrane and then passing them through a seave to create large amounts of fillable and targeted nanovesicles.  Research findings are published in journal Cancer Research.

“Currently, natural nanovesicles can be harvested from cell culture supernatant (the fluid surrounding cultured cells) and they are fillable,” said Yuan Wan, a postdoctoral fellow in biomedical engineering, Penn State. “However, there are two problems using them for cancer treatment. There aren’t enough nanovesicles produced in short timescales and they do not have targeting effect.”

“Pushing the cells through a filter is the engineered way to produce lots of nanovesicles,” said Zheng. “This approach enables us to create nanovesicles with different ligands targeting different types of tumors in about 30 minutes to meet actual needs,” said Zheng. “With this approach, we also can put different types of ligands on a nanovesicle. We could have one ligand that targets while another ligand says, ‘don’t eat me.'”

Reference: Wan, Yuan, Lixue Wang, Chuandong Zhu, Qin Zheng, Guoxiang Wang, Jinlong Tong, Yuan Fang, Yiqiu Xia, Gong Cheng, Xia He, and Si-Yang Zheng. “Aptamer-Conjugated Extracellular Nanovesicles for Targeted Drug Delivery.” Cancer Research 78, no. 3 (2017): 798-808. doi:10.1158/0008-5472.can-17-2880.

Research funding: Nanjing Science and Technology Development Foundation, Jiangsu Provincial Medical Youth Talent Award, Natural Science Foundation of Jiangsu Province, U.S. National Institutes of Health.

Adapted from press release by Penn State.

New targeted epigenetic therapy for lymphoma shows promise

New compounds targeting epigenetics have shown promise in treating patients with lymphoma, according to data presented at the Targeted Anticancer Therapies International Congress 2018 in Paris, France. ESMO’s phase-I oncology meeting featured early clinical studies with BET inhibitors and EZH2 inhibitors.

Dr. Anastasios Stathis, head of the New Drugs Development Unit of the Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland, was one of the first oncologists to research this field. He said BET inhibitors had shown some activity in leukemia, lymphoma and also a rare and aggressive solid tumor driven by a translocation involving BET genes called NUT carcinoma. His previous phase I research on the first-in-class BET inhibitor birabresib (OTX015/MK-8628) showed some activity in diffuse large B-cell lymphoma, providing proof-of-concept for this approach. (1)

Subsequently, birabresib was used on a single-patient compassionate basis in four patients with NUT carcinoma. Stathis said: “This was the first evidence that preclinical findings with BET inhibitors in models of NUT carcinoma could be translated into activity in patients.” (2)

Multiple BET inhibitors have been studied in clinical trials, and preliminary results have confirmed that they may be effective in patients with diffuse large B-cell lymphoma and NUT carcinoma. (3) Some of the significant side effects include Thrombocytopaenia which appears to be dose-limiting and is reversible and not accompanied by major bleeding events, fatigue and gastrointestinal symptoms.

Regarding activity, patients do eventually progress on treatment, and the duration of response is unknown. Stathis said: “It’s not clear what the real clinical impact of BET inhibitors could be. Compounds approved for lymphoma in the last five years had single-agent phase-I response rates above 30%, but activity with BET inhibitors is less than 30%. The hope is to identify the patients that would benefit most and test BET inhibitors in combination with other compounds. Also, there are new classes of BET inhibitors in preclinical studies, and we need to wait to see if they have better activity.”

Another area where clinical data is emerging is related to EZH2 inhibitors for which data will be presented at Targeted Anticancer Therapies International Congress 2018. EZH2 is a protein that exhibits relatively frequent mutations in lymphoma. Results will be presented from a study in patients with B-cell lymphoma showing evidence of antitumor activity with an EZH2 inhibitor, which was well tolerated and had manageable toxicities. (4) Study author Dr. Adrian Senderowicz of Constellation Pharmaceuticals, Cambridge, US, said: “If approved by health authorities, EZH2 inhibition may become a new treatment paradigm in relapse or refractory EZH2 mutant follicular lymphoma patients.”

A previous study showed that another EZH2 inhibitor, tazemetostat, induced objective response rates of 92% in patients with EZH2 mutant follicular lymphoma and 26% in those with the wild-type. (5) Stathis said: “The question is whether it makes sense to treat patients without the mutation since the response is so much lower. However, these patients do show some response and researchers want to know why.”

Stathis said: “We do have proof, and we will see further evidence at TAT 2018, that epigenetics are a promising target in lymphomas.”

Citations:

1 Amorim S, Stathis A, Gleeson M, et al. Bromodomain inhibitor OTX015 in patients with lymphoma or multiple myeloma: a dose-escalation, open-label, pharmacokinetic, phase 1 study. Lancet Haematol. 2016;3(4):e196-204. doi: 10.1016/S2352-3026(16)00021-1.

2 Stathis A, Zucca E, Bekradda M, et al. Clinical Response of Carcinomas Harboring the BRD4-NUT Oncoprotein to the Targeted Bromodomain Inhibitor OTX015/MK-8628. Cancer Discov. 2016;6(5):492-500. doi: 10.1158/2159-8290.CD-15-1335.

3 Stathis A, Bertoni F. BET Proteins as Targets for Anticancer Treatment. Cancer Discov. 2018;8(1):24-36. doi: 10.1158/2159-8290.CD-17-0605.

4 Abstract 42O ‘A Phase 1 Study of CPI-1205, a Small Molecule Inhibitor of EZH2, Preliminary Safety in Patients with B-Cell Lymphomas’: presented by Adrian Senderowicz during Proffered Paper Session 2 on Tuesday, 6 March, 11:00 to 12:30 (CET) in Room Scene AB.

5 Morschhauser F, Salles G, McKay P, et al. Interim report from a phase 2 multicenter study of tazemetostat, an EZH2 inhibitor, in patients with relapsed or refractory B-cell non-Hodgkin lymphomas. Hematol Oncol. 2017;35(S2):24-25. https://doi.org/10.1002/hon.2437_3

Adapted from press release by European Society of Medical Oncology.

Hemanthamine found in Daffodils has anti-cancer properties

Researchers from Université Libre de Bruxelles discover that alkaloid found in Daffodils has anti-cancer properties. This alkaloid called haemanthamine works by triggering activation of anti-tumor surveillance pathway. This study was led by Dennis Lafontaine and is published in journal Structure.

Structure of Ribosome. Credit ULB

Researchers found that this compound binds to the ribosome and blocks the production of proteins. Haemanthamine also inhibits the production of these ribosomes in the nucleolus. This nucleolar stress triggers the activation of an anti-tumoral surveillance pathway leading to the stabilization of the protein p53 and the elimination of cancer cells.

In the near future, the team of Denis Lafontaine, in collaboration with Veronique Mathieu (Faculty of Pharmacy- ULB), will test the effect on ribosome biogenesis and function of four Amaryllidaceae alkaloids, representative of the chemical diversity of these molecules. Their goal will be to identify the most promising chemical backbone to be further developed as a lead compound in cancer therapeutics.

Reference: Pellegrino, Simone, Mélanie Meyer, Christiane Zorbas, Soumaya A. Bouchta, Kritika Saraf, Stephen C. Pelly, Gulnara Yusupova, Antonio Evidente, Véronique Mathieu, Alexander Kornienko, Denis L.j. Lafontaine, and Marat Yusupov. “The Amaryllidaceae Alkaloid Haemanthamine Binds the Eukaryotic Ribosome to Repress Cancer Cell Growth.” Structure, 2018. doi:10.1016/j.str.2018.01.009.

Adapted from press release by Université Libre de Bruxelles.

Metabolomics is an useful tool for personalized cancer management

Metabolomics, the analysis of the complete set of metabolites in a defined biological compartment, is a relatively novel approach. Metabolomics studies have been successfully applied to get a better understanding of many diseases, including a number of neoplastic processes. In this context, it is important to underline that cancer patients exhibit metabolic profiles that are different from those of healthy individuals and patients with benign diseases. Moreover, the site, the stage, and the location of the tumors have been shown to further alter the metabolic composition.

Currently, tumors are defined not only by their location but also by their molecular characteristics. The identification of specific mutations in tumors has started to play a critical role when determining therapeutic treatments. However, that information is not currently available for the majority of cancers, and the existing biomarkers are far from being optimal. Furthermore, there is considerable heterogeneity within the current definitions of pathological process, exemplified by the fact that patients who are given an identical diagnosis react differently to the same therapy and have different outcomes. In this context, metabolomics, in combination with other “omics” approaches, could contribute to get a deeper insight into the molecular mechanisms underlying pathological processes, thus facilitating the classification of patients and their therapeutic treatment.

Precision medicine promises to tailor therapies for each individual by delivering more effective drug treatments, while avoiding or reducing adverse drug reactions. Towards this end, considerable efforts have been made over the last few years in the field of pharmacogenomics, with a focus on genotyping and identifying specific genetic variations associated with drug response. However, clinical pharmacology would benefit from the introduction of new methodologies capable of providing information that could complement this genomic information. This is necessary because drug metabolism and utilization involves many different enzymes, multiple organs, several compartments and even the microbiome, being not always possible to screen for all possible genetic or tissue variants. Furthermore, because drug metabolism varies with ethnicity, age, gender, weight, height and diet – as well as other environmental and physiological variables – it can be particularly challenging to predict how an individual will respond to a drug based on their genotype alone.

In this context, the ability to directly and accurately assess the biological phenotype of patients will be a critical component in determining the correct drug treatment or in predicting the response following a therapeutic treatment. Metabolites are the final products of cellular regulatory processes and their levels can be regarded as the ultimate response of biological systems to genetic and environmental changes. Similarly, to the terms ‘transcriptome’ or ‘proteome’, the set of metabolites synthetized by a biological system constitutes its ‘metabolome’. Since the metabolome is closely tied to the genotype of an individual as well as its physiology and the surrounding environment, metabolomics offers a unique opportunity to look at genotype-phenotype and genotype-environment relationships. Metabolomics is closely linked to the overall physiopathological status of an individual. Thus, metabolomics may incorporate the biochemical events of thousands of small molecules in cells, tissues, organs, or biological fluids. Disease state or drug exposure could alter such metabolite composition in qualitative and quantitative terms generating complex metabolic signatures. The analysis of these signatures can potentially provide useful information for the diagnosis and prognosis of patients as well as for predicting pharmacological responses to specific interventions. Additionally, specific metabolic signatures occur after drug treatment, thus providing information from pathways targeted or affected by drug therapy.

This review provides specific examples of metabolomics applications in the field of clinical pharmacology and precision medicine with a focus on the therapeutic management of cancer and in the translation of these results to the clinics.

Citation: Puchades-Carrasco, Leonor, and Antonio Pineda- Lucena. “Metabolomics Applications in Precision Medicine: An Oncological Perspective.” Current Topics in Medicinal Chemistry 17, no. 24 (2017). doi:10.2174/1568026617666170707120034.

Adapted from press release by Bentham science publishers.

Finding new uses for old medication using computer program DrugPredict

Researchers at Case Western Reserve University School of Medicine have developed a computer program called DrugPredict to discover new indications for old drugs. This program matches existing data about FDA-approved drugs to diseases, and predicts potential drug efficacy.

In a recent study published in Oncogene, the researchers successfully translated DrugPredict results into the laboratory, and showed common pain medications non-steroidal anti-inflammatory drugs, also known as NSAIDs could have applications for epithelial ovarian cancer.

DrugPredict was developed by co-first author QuanQiu Wang of ThinTek, LLC, and co-senior author Rong Xu, PhD, associate professor of biomedical informatics in the department of population and quantitative health sciences at Case Western Reserve University School of Medicine. The program works by connecting computer-generated drug profiles including mechanisms of action, clinical efficacy, and side effects with information about how a molecule may interact with human proteins in specific diseases, such as ovarian cancer.

DrugPredict searches databases of FDA-approved drugs, chemicals, and other naturally occurring compounds. It finds compounds with characteristics related to a disease-fighting mechanism. These include observable characteristics (phenotypes) and genetic factors that may influence drug efficacy. Researchers can collaborate with Xu to input a disease into DrugPredict and receive an output list of drugs or potential drugs with molecular features that correlate with strategies to fight the disease.

In the Oncogene study, DrugPredict produced a prioritized list of 6,996 chemicals with potential to treat epithelial ovarian cancer. At the top of the list were 15 drugs already FDA-approved to treat the cancer, helping to validate the DrugPredict approach. Of other FDA-approved medications on the list, NSAIDs ranked significantly higher than other drug classes. The researchers combined the DrugPredict results with anecdotal evidence about NSAIDs and cancer before confirming DrugPredict results in their laboratory experiments.

Citation: Nagaraj, A. B., Q. Q. Wang, P. Joseph, C. Zheng, Y. Chen, O. Kovalenko, S. Singh, A. Armstrong, K. Resnick, K. Zanotti, S. Waggoner, R. Xu, and A. Difeo. “Using a novel computational drug-repositioning approach (DrugPredict) to rapidly identify potent drug candidates for cancer treatment.” Oncogene, 2017.

DOI: 10.1038/onc.2017.328

Funding: Gynecological Cancer Translation Research Program, Case Comprehensive Cancer Center, The Mary Kay Foundation, NIH/Eunice Kennedy Shriver National Institute Of Child Health & Human Development.

Adapted from press release by Case Western Reserve University.

Novel and unique DNA vaccine to fight effectively against cancer antigen

Scientists at The Wistar Institute and Inovio pharmaceuticals, Inc. have devised a unique deoxyribonucleic acid (DNA) vaccine approach through molecular design to boost the immune responses induced against one of the most important cancer antigen targets. Research results were published in the journal Molecular Therapy.

Cancer immunotherapy approaches, designed to harness the body’s natural immune defenses to focus on and kill cancer cells, are showing great promise for cancer treatment and prevention. DNA vaccines can induce immunity through the delivery by an intramuscular injection of a sequence of synthetically designed DNA that contains the instructions for the immune cells in the body to become activated and target a particular antigen against which an immunologic response is wanted.

Despite being specific for cancer cells, cancer tumor-associated antigens generally trigger weak immune responses as a result of they’re recognized as self-antigens and also the body has in place natural mechanisms of immune acceptance, or “Tolerance”, that forestall autoimmunity and also additionally limit the efficacy of cancer vaccines. This is often the case of Wilm’s tumor gene 1 (WT1), a cancer tumor antigen that’s overexpressed in many varieties of cancer and possibly plays a key role in driving tumor development. vaccine approaches against WT1 thus far haven’t appeared promising because of immune tolerance leading to poor immune responses against cancers expressing WT1.

Wistar scientists have developed a unique WT1 deoxyribonucleic acid (DNA) vaccine employing a strategically changed DNA sequence that tags the WT1 as foreign to the host immune system breaking tolerance in animal models.

“This is an important time in the development of anti-DNA cancer immune therapy approaches. This team has developed an approach that may play an important role in generating improved immunity to WT1 expressing cancers,”said David B. Weiner, Ph.D., Executive Vice President and Director of the Vaccine Center at The Wistar Institute and the W.W. Smith Charitable Trust Professor in Cancer Research, and senior author of the study.”These immune responses represent a unique tool for potentially treating patients with multiple forms of cancer. Our vaccine also provides an opportunity to combine this approach with another immune therapy approach, checkpoint inhibitors, to maximize possible immune therapy impact on specific cancers.”

The team lead by Weiner has optimized the dna vaccine employing a artificial dna sequence for WT1 that, while maintaining a very high similarity with the native sequence, contains new modified sequences that differ from native WT1 in an attempt to render it more recognizable by the host immune system. The novel WT1 vaccine was superior to a more traditional native WT1 vaccine because it was able to break immune tolerance and induce long-term immune memory. Significantly, the vaccine also stimulated a therapeutic anti-tumor response against leukemia in mice.

Citation: Walters, Jewell N., Bernadette Ferraro, Elizabeth K. Duperret, Kimberly A. Kraynyak, Jaemi Chu, Ashley Saint-Fleur, Jian Yan, Hy Levitsky, Amir S. Khan, Niranjan Y. Sardesai, and David B. Weiner. “A Novel DNA Vaccine Platform Enhances Neo-antigen-like T Cell Responses against WT1 to Break Tolerance and Induce Anti-tumor Immunity.” Molecular Therapy, 2017. doi:10.1016/j.ymthe.2017.01.022.
Research funding: Inovio Pharmaceuticals, Inc. Basser Center for BRCA/Abramson Cancer CenterWeiner, W.W. Smith Charitable Trust Professorship for Cancer Research.
Adapted from press release by The Wistar Institute.

Gene therapy using lipid based nanoparticles

Lipid nanoparticles (SLNs and NLCs) are regarded as highly promising systems for delivering nucleic acids in gene therapy. Literature review by researchers at PharmaNanoGene describes these systems and their main advantages in gene therapy, such as their capacity to protect the gene material against degradation, to facilitate cell and nucleus internalization and to boost the transfection process.


View of lipid nanoparticles.
View of lipid nanoparticles. Credit: UPV/EHU

“At PharmaNanoGene we are working on the design and evaluation of SLNs for treating some of these diseases using gene therapy. We are studying the relationship between formulation factors and the processes involving the intracellular internalisation and disposition of the genetic material that condition the effectiveness of the vectors and which is essential in the optimisation process, and for the first time we have demonstrated the capacity of SLNs to induce the synthesis of a protein following their intravenous administration in mice,” they stressed.

The publication also includes other pieces of work by this University of the Basque Country research group on the application of SLNs in the treatment of rare diseases, such as chromosome-X-linked juvenile retinoschisis, a disorder in which the retina becomes destructured due to a deficiency in the protein retinoschisin.

 “One of the main achievements of our studies in this field has been to demonstrate, also for the first time, the capacity of a non-viral vector to transfect the retina of animals lacking the gene that encodes this protein and partially restore its structure, showing than non-viral gene therapy is a viable, promising therapeutic tool for treating degenerative disorders of the retina,” specified the researchers.
The application of SLNs for treating Fabry disease, a serious, multi-system metabolic disorder of a hereditary nature, has also been studied at PharmaNanoGene.

 “This is a monogenic disease linked to the X-chromosome which is caused by various gene mutations in the gene that encodes the galactosidase A enzyme. In cell models of this disease we have demonstrated the capacity of SLNs to induce the synthesis of galactosidase A enzyme”. They have also reviewed the application of lipid nanoparticles to the treatment of infectious diseases: “Our work in this field shows that SLNs with RNA interference are capable of inhibiting a replicon of the hepatitis C virus in vitro, which was used as proof-of-concept of the use of SLN-based vectors as a new therapeutic strategy for treating this infection and others related to it”.

Citation: Ana del Pozo-Rodríguez, María Ángeles Solinís, Alicia Rodríguez-Gascón, Applications of lipid nanoparticles in gene therapy, European Journal of Pharmaceutics and Biopharmaceutics, Volume 109, December 2016, Pages 184-193.
DOI: 10.1016/j.ejpb.2016.10.016.
Adapted from press release by University of the Basque Country.

Research in mice show antioxidants in blue maize have protective effect against metabolic syndrome

A new study shows that a rat model of metabolic syndrome fed a high-sugar and high-cholesterol diet and given blue maize extract showed significant improvement in systolic blood pressure, high density lipoprotein (HDL) cholesterol, and triglyceride levels compared to those not given the extract. The natural antioxidants present in blue maize may help protect against metabolic syndrome, cardiovascular disease, diabetes, and cancer, raising interest in using blue maize as a component of functional foods and nutraceuticals, according to an article published in Journal of Medicinal Food.

Credit: Pexels /Pixabay

In the article Rosa Isela Guzman-Geronimoa and coauthors from Universidad Veracruzana, Instituto Tecnologico de Veracruz, and Unidad Oaxaca/Calle Hornos, Mexico, report that the animals fed a high-sugar and high-cholesterol diet that received blue maize extract had a significantly smaller increase in abdominal fat compared to the abdominal fat gain in rats that did not receive the extract.

“Anti-obesity food materials are always in demand, and this study brings out not only the importance of blue maize in controlling adipocity, but also the potential role of cholesterol in the development of obesity,” says Journal of Medicinal Food Editor-in-Chief Sampath Parthasarathy, MBA, PhD, Florida Hospital Chair in Cardiovascular Sciences and Interim Associate Dean, College of Medicine, University of Central Florida.

Citation: Guzmán-Gerónimo Rosa Isela, Alarcón-Zavaleta Tania Margarita, Oliart-Ros Rosa María, Meza-Alvarado José Enrique, Herrera-Meza Socorro, and Chávez-Servia José Luis. “Blue Maize Extract Improves Blood Pressure, Lipid Profiles, and Adipose Tissue in High-Sucrose Diet-Induced Metabolic Syndrome in Rats.” Journal of Medicinal Food. December 2016, ahead of print. DOI:10.1089/jmf.2016.0087