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Eight Subcellular Pathologies driving Chronic Metabolic Diseases – Methods for Mapping Bioelectronic Adjustable Measurements as potential new Therapeutics: Impact on Pharmaceuticals in Use

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Eight Subcellular Pathologies driving Chronic Metabolic Diseases – Methods for Mapping Bioelectronic Adjustable Measurements as potential new Therapeutics: Impact on Pharmaceuticals in Use

Curators:

• Cardiovascular Expertise – Dr. Justin D. Pearlman, MD, PhD, FACC
• Pharmacology and Oncology Expertise – Dr. Stephen J. Williams, PhD
• Principal Investigator, initiator of the project – Aviva Lev-Ari, PhD, RN

 

THE VOICE of Aviva Lev-Ari, PhD, RN

In this curation we wish to present two breaking through goals:

Goal 1:

Exposition of a new direction of research leading to a more comprehensive understanding of Metabolic Dysfunctional Diseases that are implicated in effecting the emergence of the two leading causes of human mortality in the World in 2023: (a) Cardiovascular Diseases, and (b) Cancer

Goal 2:

Development of Methods for Mapping Bioelectronic Adjustable Measurements as potential new Therapeutics for these eight subcellular causes of chronic metabolic diseases. It is anticipated that it will have a potential impact on the future of Pharmaceuticals to be used, a change from the present time current treatment protocols for Metabolic Dysfunctional Diseases.

According to Dr. Robert Lustig, M.D, an American pediatric endocrinologist. He is Professor emeritus of Pediatrics in the Division of Endocrinology at the University of California, San Francisco, where he specialized in neuroendocrinology and childhood obesity, there are eight subcellular pathologies that drive chronic metabolic diseases.

These eight subcellular pathologies can’t be measured at present time.

In this curation we will attempt to explore methods of measurement for each of these eight pathologies by harnessing the promise of the emerging field known as Bioelectronics.

Unmeasurable eight subcellular pathologies that drive chronic metabolic diseases

1. Glycation
2. Oxidative Stress
3. Mitochondrial dysfunction [beta-oxidation Ac CoA malonyl fatty acid]
4. Insulin resistance/sensitive [more important than BMI], known as a driver to cancer development
5. Membrane instability
6. Inflammation in the gut [mucin layer and tight junctions]
7. Epigenetics/Methylation
8. Autophagy [AMPKbeta1 improvement in health span]

Diseases that are not Diseases: no drugs for them, only diet modification will help

Image source

Robert Lustig, M.D. on the Subcellular Processes That Belie Chronic Disease

https://www.youtube.com/watch?v=Ee_uoxuQo0I

 

Exercise will not undo Unhealthy Diet

Image source

Robert Lustig, M.D. on the Subcellular Processes That Belie Chronic Disease

https://www.youtube.com/watch?v=Ee_uoxuQo0I

 

These eight Subcellular Pathologies driving Chronic Metabolic Diseases are becoming our focus for exploration of the promise of Bioelectronics for two pursuits:

1. Will Bioelectronics be deemed helpful in measurement of each of the eight pathological processes that underlie and that drive the chronic metabolic syndrome(s) and disease(s)?
2. IF we will be able to suggest new measurements to currently unmeasurable health harming processes THEN we will attempt to conceptualize new therapeutic targets and new modalities for therapeutics delivery – WE ARE HOPEFUL

In the Bioelecronics domain we are inspired by the work of the following three research sources:

1. Biological and Biomedical Electrical Engineering (B2E2) at Cornell University, School of Engineering https://www.engineering.cornell.edu/bio-electrical-engineering-0
2. Bioelectronics Group at MIT https://bioelectronics.mit.edu/
3. The work of Michael Levin @Tufts, The Levin Lab

Michael Levin is an American developmental and synthetic biologist at Tufts University, where he is the Vannevar Bush Distinguished Professor. Levin is a director of the Allen Discovery Center at Tufts University and Tufts Center for Regenerative and Developmental Biology. Wikipedia

Born: 1969 (age 54 years), Moscow, Russia

Education: Harvard University (1992–1996), Tufts University (1988–1992)

Affiliation: University of Cape Town

Research interests: Allergy, Immunology, Cross Cultural Communication

Awards: Cozzarelli prize (2020)

Doctoral advisor: Clifford Tabin

Fields: Developmental biology, synthetic biology

SOURCE

https://www.google.com/search?q=Michael+Levin+%40Tufts&oq=Michael+Levin+%40Tufts&aqs=chrome..69i57j69i58.894128314j0j15&sourceid=chrome&ie=UTF-8

Most recent 20 Publications by Michael Levin, PhD

SOURCE

https://facultyprofiles.tufts.edu/michael-levin-1/publications

SCHOLARLY ARTICLE

The nonlinearity of regulation in biological networks

1 Dec 2023npj Systems Biology and Applications9(1)

Co-authorsManicka S, Johnson K, Levin M…1 more

VIEW PDF10.1038/S41540-023-00273-W

3

SCHOLARLY ARTICLE

Toward an ethics of autopoietic technology: Stress, care, and intelligence

1 Sep 2023BioSystems231

Co-authorsWitkowski O, Doctor T, Solomonova E…2 more

VIEW PDF10.1016/J.BIOSYSTEMS.2023.104964

SCHOLARLY ARTICLE

Closing the Loop on Morphogenesis: A Mathematical Model of Morphogenesis by Closed-Loop Reaction-Diffusion

14 Aug 2023Frontiers in Cell and Developmental Biology11:1087650

Co-authorsGrodstein J, McMillen P, Levin M

VIEW PDF10.3389/FCELL.2023.1087650

SCHOLARLY ARTICLE

Correcting instructive electric potential patterns in multicellular systems: External actions and endogenous processes.

30 Jul 2023Biochim Biophys Acta Gen Subj1867(10):130440

Co-authorsCervera J, Levin M, Mafe S

VIEW MORE INFO10.1016/J.BBAGEN.2023.130440

SCHOLARLY ARTICLE

Regulative development as a model for origin of life and artificial life studies

1 Jul 2023BioSystems229

Co-authorsFields C, Levin M

10.1016/J.BIOSYSTEMS.2023.104927

1

SCHOLARLY ARTICLE

The Yin and Yang of Breast Cancer: Ion Channels as Determinants of Left–Right Functional Differences

1 Jul 2023International Journal of Molecular Sciences24(13)

Co-authorsMasuelli S, Real S, McMillen P…3 more

VIEW PDF10.3390/IJMS241311121

SCHOLARLY ARTICLE

Bioelectricidad en agregados multicelulares de células no excitables- modelos biofísicos

Jun 2023Revista Española de Física32(2)

Co-authorsCervera J, Levin M, Mafé S

SCHOLARLY ARTICLE

Bioelectricity: A Multifaceted Discipline, and a Multifaceted Issue!

1 Jun 2023Bioelectricity5(2):75

Co-authorsDjamgoz MBA, Levin M

10.1089/BIOE.2023.0022.EDITORIAL

SCHOLARLY ARTICLE

Control Flow in Active Inference Systems – Part I: Classical and Quantum Formulations of Active Inference

1 Jun 2023IEEE Transactions on Molecular, Biological, and Multi-Scale Communications9(2):235-245

Co-authorsFields C, Fabrocini F, Friston K…4 more

10.1109/TMBMC.2023.3272150

2

SCHOLARLY ARTICLE

Control Flow in Active Inference Systems – Part II: Tensor Networks as General Models of Control Flow

1 Jun 2023IEEE Transactions on Molecular, Biological, and Multi-Scale Communications9(2):246-256

Co-authorsFields C, Fabrocini F, Friston K…4 more

10.1109/TMBMC.2023.3272158

2

SCHOLARLY ARTICLE

Darwin’s agential materials: evolutionary implications of multiscale competency in developmental biology

1 Jun 2023Cellular and Molecular Life Sciences80(6)

Co-authorsLevin M

VIEW PDF10.1007/S00018-023-04790-Z

1

SCHOLARLY ARTICLE

Morphoceuticals: Perspectives for discovery of drugs targeting anatomical control mechanisms in regenerative medicine, cancer and aging

1 Jun 2023Drug Discovery Today28(6)

Co-authorsPio-Lopez L, Levin M

VIEW PDF10.1016/J.DRUDIS.2023.103585

1

SCHOLARLY ARTICLE

Morphoceuticals: Perspectives for discovery of drugs targeting anatomical control mechanisms in regenerative medicine, cancer and aging

Jun 2023DRUG DISCOVERY TODAY28(6):1-13

Co-authorsPio-Lopez L, Levin M

VIEW MORE INFO10.1016/J.DRUDIS.2023.103585THIS

SCHOLARLY ARTICLE

Cellular signaling pathways as plastic, proto-cognitive systems: Implications for biomedicine

12 May 2023Patterns4(5)

Co-authorsMathews J, Chang A, Devlin L…1 more

VIEW PDF10.1016/J.PATTER.2023.100737

3

SCHOLARLY ARTICLE

Making and breaking symmetries in mind and life

14 Apr 2023Interface Focus13(3)

Co-authorsSafron A, Sakthivadivel DAR, Sheikhbahaee Z…3 more

VIEW PDF10.1098/RSFS.2023.0015

SCHOLARLY ARTICLE

The scaling of goals from cellular to anatomical homeostasis: an evolutionary simulation, experiment and analysis

14 Apr 2023Interface Focus13(3)

Co-authorsPio-Lopez L, Bischof J, LaPalme JV…1 more

VIEW PDF10.1098/RSFS.2022.0072

1

SCHOLARLY ARTICLE

The collective intelligence of evolution and development

Apr 2023Collective Intelligence2(2):263391372311683SAGE Publications

Co-authorsWatson R, Levin M

VIEW PDF10.1177/26339137231168355

SCHOLARLY ARTICLE

Bioelectricity of non-excitable cells and multicellular pattern memories: Biophysical modeling

13 Mar 2023Physics Reports1004:1-31

Co-authorsCervera J, Levin M, Mafe S

10.1016/J.PHYSREP.2022.12.003

2

SCHOLARLY ARTICLE

There’s Plenty of Room Right Here: Biological Systems as Evolved, Overloaded, Multi-Scale Machines

1 Mar 2023Biomimetics8(1)

Co-authorsBongard J, Levin M

VIEW PDF10.3390/BIOMIMETICS8010110

4

SCHOLARLY ARTICLE

Transplantation of fragments from different planaria: A bioelectrical model for head regeneration

7 Feb 2023Journal of Theoretical Biology558

Co-authorsCervera J, Manzanares JA, Levin M…1 more

VIEW PDF10.1016/J.JTBI.2022.111356

SCHOLARLY ARTICLE

Bioelectric networks: the cognitive glue enabling evolutionary scaling from physiology to mind

1 Jan 2023Animal Cognition

Co-authorsLevin M

VIEW PDF10.1007/S10071-023-01780-3

2

SCHOLARLY ARTICLE

Biological Robots: Perspectives on an Emerging Interdisciplinary Field

1 Jan 2023Soft Robotics

Co-authorsBlackiston D, Kriegman S, Bongard J…1 more

10.1089/SORO.2022.0142

1

SCHOLARLY ARTICLE

Cellular Competency during Development Alters Evolutionary Dynamics in an Artificial Embryogeny Model

1 Jan 2023Entropy25(1)

Co-authorsShreesha L, Levin M

VIEW PDF10.3390/E25010131

5

SCHOLARLY ARTICLE

Endless forms most beautiful 2.0: teleonomy and the bioengineering of chimaeric and synthetic organisms (July, blac073, 2022)

1 Jan 2023BIOLOGICAL JOURNAL OF THE LINNEAN SOCIETY138(1):141

Co-authorsClawson WP, Levin M

VIEW PDFVIEW MORE INFO10.1093/BIOLINNEAN/BLAC116

SCHOLARLY ARTICLE

Future medicine: from molecular pathways to the collective intelligence of the body

1 Jan 2023Trends in Molecular Medicine

Co-authorsLagasse E, Levin M

10.1016/J.MOLMED.2023.06.007

THE VOICE of Dr. Justin D. Pearlman, MD, PhD, FACC

PENDING

THE VOICE of  Stephen J. Williams, PhD

Ten TakeAway Points of Dr. Lustig’s talk on role of diet on the incidence of Type II Diabetes

 

1. 25% of US children have fatty liver
2. Type II diabetes can be manifested from fatty live with 151 million  people worldwide affected moving up to 568 million in 7 years
3. A common myth is diabetes due to overweight condition driving the metabolic disease
4. There is a trend of ‘lean’ diabetes or diabetes in lean people, therefore body mass index not a reliable biomarker for risk for diabetes
5. Thirty percent of ‘obese’ people just have high subcutaneous fat.  the visceral fat is more problematic
6. there are people who are ‘fat’ but insulin sensitive while have growth hormone receptor defects.  Points to other issues related to metabolic state other than insulin and potentially the insulin like growth factors
7. At any BMI some patients are insulin sensitive while some resistant
8. Visceral fat accumulation may be more due to chronic stress condition
9. Fructose can decrease liver mitochondrial function
10. A methionine and choline deficient diet can lead to rapid NASH development

 

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CytoReason is re-defining the Context of the Immune System for Drug Discovery

Posted in Adaptive Immune Response to Biomaterials and Tissue Repair, BioTechnology - Venture Creation, Engineering Better T Cells, Immune Engineering, Immune Modulatory, Immunodiagnostics, Immunotherapy, NK Cell-Based Cancer Immunotherapy, Protection Against Autoimmune Disease, Synergistic Innate and Adaptive Immunotherapy on May 21, 2019| Leave a Comment »

CytoReason is re-defining the Context of the Immune System for Drug Discovery

Reporter: Aviva Lev-Ari, PhD, RN

 

CytoReason is re-defining the context of the immune system at a cellular level in order to better understand disease and support more effective drug discovery and development.

Our leading-edge machine-learning driven approach identifies “cause and effect” of the gene/cell/cytokine relationships that lie at the heart of treating disease.

Faster and more accurately than ever before.

CytoReason’s mission is to simulate the cells that can stimulate discovery of:​

• New targets for treating disease

• New insights to mechanism of actions (both of disease and drugs)

• Differences in responses to both disease and treatment

• Which diseases a drug can impact

We have developed a unique machine-learning driven approach to “seeing” the cells that can make the difference in patients seeing a better life.

The insights our approach generates, enable pharmaceutical and biotech companies to make the right decisions, at the right time, in the drug discovery and development programs that bring better therapies.

Based on cutting edge technologies, trained on data that would normally be impossible to access, and steered by leading biological and data science researchers, our approach is underpinned by three core principles:​

SOURCE

https://www.cytoreason.com/

Press Release

https://docs.wixstatic.com/ugd/216dd2_b715f2c29a8c496eb65315d332a7077e.pdf

Case Studies

Click one of the buttons below to view a short case study presention:

IBD: Anti-TNFα Pre-Treatment Response

Atopic Dermatitis: IL4 MoA

Melanoma: Target & Biomarker ID

Collaboration & Results

Working with leading global pharma and biotech companies and key research institutions, our results help guide R&D decision making.

​

​

​

​

​

​

Results

Our platform is tried and tested, producing real results with validation

•    Discovered: New cellular players in melanoma microenvironment

•    Discovered: New IL4 mechanism of action in atopic dermatitis

•    Discovered: Novel pre-treatment biomarkers in IBD anti-TNFα therapy

•    Discovered: 355 previously unreported cell/cytokine interactions (view infographic)

Publications

Science is the backbone of our methodologies and applications, and must stand the test of scientific scrutiny.  To date we have 16 research papers published in top quality peer-reviewed scientific journals, including four in 2018 alone – 3 of which were published in journals from the Nature group

Click here to see our publications

SOURCE

https://www.cytoreason.com/

 

Shen-Orr told Forbes in an article published late last month that CytoReason’s tech is able to calculate immune age in one of two ways: “Via cell-subset composition nearest neighbor approach or based on a gene expression signature where the genes are predictive of the cell-subsets composition, and they test for their enrichment in the gene expression pattern of the sample. The immune profiles of individuals are used to predict immune changes based on a machine learning methodology deployed on data on a range of cell-subsets. ”

“The immune age is a biological clock that will help to identify, the decline and progress in immunity that occurs in old age, to determine preventive measures and develop new treatment modalities to minimize chronic disease and death,” he added.

CytoReason’s tech has so far yielded two pending patents, 10 commercial and scientific collaborations, and 16 peer-reviewed publications.

Harel says it was a combination of forces that made CytoReason’s immune-focused methodology work: Big Data, machine learning, and biology. He describes it as “the intersection of computer science and biology.”

SEE ALSO: The Future Of Medicine: Israeli Scientists Unveil New Tech To 3D-Print Personalized Drugs

 

Professor Magdassi tells NoCamels that with 3D printing of hydrogels, molecules that are soluble in water, scientists can improve the performance of the drug through its delivery. For example, “the hydrogel once ingested can be designed to swell, releasing two, or three, or four drugs at a time [or with a delay] or it can be designed not to swell, depending on what we are trying to achieve.”

“The drug can be tailored to the patient because of the unique shape or structure of the hydrogel and/or its release behavior,” Professor Magdassi explains.

Currently, there is one 3D-printed drug on the market. In 2015, the US Food and Drug Administration (FDA) approved Spritam, a 3D-printed powdered drug in pill form for the treatment of epileptic seizures, designed to dissolve faster than other pills.

SOURCE

http://nocamels.com/2018/11/future-medicine-israel-3d-print-personalized-drugs/

 

Quantifying The Age Of Our Immune System Could Bring Us Some Steps Closer To Precision Medicine

Yiannis Mouratidis

Contributor

Science

Last January, CytoReason announced an agreement with Pfizer, in which the latter will leverage the former’s technology to create cell-based models of the immune system. According to the agreement, CytoReason will receive an undisclosed amount in the low double-digit millions of U.S. dollars from Pfizer in access fees, research support and success-based payments. Prof. Shen-Orr concluded, “The immune age is a biological clock that will help to identify, the decline and progress in immunity that occurs in old age, to determine preventive measures and develop new treatment modalities to minimize chronic disease and death.”

SOURCE

https://www.forbes.com/sites/yiannismouratidis/2019/04/29/quantifying-the-age-of-our-immune-system-could-bring-us-some-steps-closer-to-precision-medicine/#15ef4e0628b3

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