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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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COVID and the brain: researchers zero in on how damage occurs

Posted in Cancer Researchers Fighting COVID-19, COVID-19, COVID-19, Human Antibody Response, Immunology, memory loss, Neurological Diseases, SARS-CoV-2, SARS-CoV-2 Viral Variants, Stroke, Treatment Protocols for COVID-19, tagged brain, brain development, Clinical trial, COVID-19, damage, health, medicine, memory loss, SARS-CoV-2 on July 8, 2021| Leave a Comment »

COVID and the brain: researchers zero in on how damage occurs

Reporter: Danielle Smolyar

Research Assistant 3 – Text Analysis for 2.0 LPBI Group’s TNS #1 – 2020/2021 Academic Internship in Medical Text Analysis (MTA)

Recent evidence has indicated that coronavirus can cause brain fog and also lead to different neurological symptoms. 

Since the beginning of the pandemic, researchers have been trying to understand how the coronavirus SARS-CoV-2 affects the brain

Image Credit: Stanislav Krasilnikov/TASS/Getty

image source:https://www.nature.com/articles/d41586-021-01693-6?utm_source=Nature+Briefing

New evidence has shown how coronavirus has caused much damage to the brain. There is a new evidence that shows that COVID-19 assault on the brain I has the power to be multipronged. What this means is that it can attack on certain Brain cells such as reduce the amount of blood flow that the brain needs to the brain tissue.

Along with brain damage COVID-19 has also caused strokes and memory loss. A neurologist at yell University Serena Spudich says, “Can we intervene early to address these abnormalities so that people don’t have long-term problems?”

We’re on 80% of the people who have been hospitalized due to COVID-19 have showed brain symptoms which seem to be correlated to coronavirus.

At the start of the pandemic a group of researchers speculated that coronavirus they can damage the brain by infecting the neurons in the cells which are important in the process of transmitting information. After further studies they found out that coronavirus has a harder time getting past the brains defense system and the brain barrier and that it does not affect the neurons in anyway.

An expert in this study indicated that a way in which SARS-CoV-2 may be able to get to the brain is by going through the olfactory mucosa which is the lining of the nasal cavity. It is found that this virus can be found in the nasal cavity which is why we swab the nose one getting tested for COVID-19.

Spudich quotes, “there’s not a tonne of virus in the brain”.

Recent studies indicate that SARS-CoV-2 have ability to infect astrocytes which is a type of cell found in the brain. Astrocytes do quite a lot that supports normal brain function,” including providing nutrients to neurons to keep them working, says Arnold Kriegstein, a neurologist at the University of California, San Francisco.

Astrocytes are star-shaped cells in the central nervous system that perform many functions, including providing nutrients to neurons.

Image Credit: David Robertson, ICR/SPL

image source: https://www.nature.com/articles/d41586-021-01693-6?utm_source=Nature+Briefing

Kriegstein and his fellow colleagues have found that SARS-CoV-2 I mostly infects the astrocytes over any of the other brain cells present. In this research they expose brain organoids which is a miniature brain that are grown from stem cells into the virus.

As quoted in the article” a group including Daniel Martins-de-Souza, head of proteomics at the University of Campinas in Brazil, reported⁶ in a February preprint that it had analysed brain samples from 26 people who died with COVID-19. In the five whose brain cells showed evidence of SARS-CoV-2 infection, 66% of the affected cells were astrocytes.”

The infected astrocytes could indicate the reasoning behind some of the neurological symptoms that come with COVID-19. Specifically, depression, brain fog and fatigue. Kreigstein quotes, “Those kinds of symptoms may not be reflective of neuronal damage but could be reflective of dysfunctions of some sort. That could be consistent with astrocyte vulnerability.”

A study that was published on June 21 they compared eight different brands of deceased people who did have COVID-19 along with 14 brains as the control. The results of this research were that they found that there was no trace of coronavirus Brain infected but they found that the gene expression was affected in some of the astrocytes.

As a result of doing all this research and the findings the researchers want to know more about this topic and how many brain cells need to be infected for there to be neurological symptoms says Ricardo Costa.

Further evidence has also been done on how SARS-CoV-2 can affect the brain by reducing its blood flow which impairs the neurons’ function which ends up killing them.

Pericytes can be found on the small blood vessels which are called capillaries and are found all throughout the body and in the brain. In a February pre-print there was a report about how SARS-CoV-2 can infect the pericyte in the brain organoids. 

David Atwell, a neuroscientist at the University College London, along with his other colleagues had published a pre-print which has evidence to show that SARS-CoV-2 odes In fact pericytes behavior. I researchers saw that in the different part of the hamsters brain SARS-CoV-2 blocks the function of receptors on the pericytes which ultimately causes the capillaries found inside the tissues to constrict.

As stated in the article, It’s a “really cool” study, says Spudich. “It could be something that is determining some of the permanent injury we see — some of these small- vessel strokes.”

Attwell brought to the attention that the drugs that are used to treat high blood pressure may in fact be used in some cases of COVID-19. Currently there are two clinical trials that are being done to further investigate this idea.

There is further evidence showing that the neurological symptoms and damage could in fact be happening because of the bodies on immune system reacting or misfiring after having COVID-19.

Over the past 15 years it has become evident that people’s immune system’s make auto antibodies which attack their own tissues says Harald Prüss in the article who has a Neuroimmunologist at the German Center for neurogenerative Diseases in Berlin. This may cause neuromyelitis optica which is when you can experience loss of vision or weakness in limbs. Harald Prüss summarized that the autoantibodies can pass through the blood brain barrier and ultimately impact neurological disorders such as psychosis.

Prüss and his colleagues published a study last year that focused on them isolating antibodies against SARS-CoV-2 from people. They found that one was able to protect hamsters from lung damage and other infections. The purpose of this was to come up with and create new treatments. During this research they found that some of the antibodies from people. They found that one was able to protect hamsters from lung damage and other infections. The purpose of this was to come up with and create new treatments. During this research they found that some of the antibodies can bind to the brain tissue which can ultimately damage it. Prüss states, “We’re currently trying to prove that clinically and experimentally,” says Prüss.

Was published online in December including Prüss sorry the blood and cerebrospinal fluid of 11 people who were extremely sick with COVID-19. These 11 people had neurological symptoms as well. All these people were able to produce auto antibodies which combined to neurons. There is evidence that when the patients were given intravenous immunoglobin which is a type of antibody it was successful.

Astrocytes, pericytes and autoantibodies we’re not the only  pathways. However it is likely that people with COVID-19 experience article symptoms for many reasons. As stated, In the article, Prüss says a key question is what proportion of cases is caused by each of the pathways. “That will determine treatment,” he says.

SOURCE: https://www.nature.com/articles/d41586-021-01693-6?utm_source=Nature+Briefing

Original article: 

Marshall, M. (2021, July 7). COVID and the brain: researchers zero in on how damage occurs. Nature News. https://www.nature.com/articles/d41586-021-01693-6

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Nir Hacohen and Marcia Goldberg, Researchers at MGH and the Broad Institute identify protein “signature” of severe COVID-19

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