BME 348 Flashcards

Regen Eng Exam 1

What is regenerative engineering?

the study of naturally occurring cell regenerative mechanisms (processes) in response to injury/disorders

the development and utilization of engineering to optimize cell regenerative processes to facilitate recovery from injury/disorders

Explain the cell regenerative processes from environmental insults to recovery?

insults → cell stimulation/injury/death — (mediating factors) → cell proliferation/regeneration → replacement of dead cells → recovery

What are different types of environmental insults?

microorganisms, toxins, mechanical injury, temp, and radiation

What are mediating factors?

cytokines and growth factors that facilitate the process from cell stimulation/injury/death to cell proliferation/regeneration

Any cell growth during the embryonic stage and post-embryonic stage prior to the establishment of adulthood is referred to as _______.

cell growth (from fertilized ovum)

When we reach adulthood, any cell growth is titled ________.

cell regeneration

All cell regeneration processes starts with cell ___.

injury

What are the major types of microorganisms?

1. viruses

2. bacteria

3. parasites

4. fungi

When viruses enter our body, they have to enter ____. If they stay in ____ or ____, they will die.

They have to enter cells. If they stay in interstitial tissue or blood they will die.

How do viruses cause cell death?

they enter our cells → release protein-based toxins → mess up cellular functional regulatory monocular pathways → cells die

Alcohol causes protein ______, meaning various protein molecules bond by amino acids. This results in _______, which causes cell death.

cross-linking results in chemical fixation

What is cell stimulation?

Cells are not injured, but they are not happy (itching and pain)→ can return to regular in minutes

True / False: The preparation/cell stimulation stage does not matter since cells are not dying

False— the prep stage is very important because once the cells sense low-level stem they can prepare and mobilize their regenerative processes.

When actual injury occurs, the body will be ready!

Most factors refer to _____, because they are the molecules that directly serve as building blocks to all these cellular structures and serve as signaling molecules that directly control the intracellular or extracellular activities.

proteins

mediating factors include _____ and ______.

cytokines and growth factors

cytokines are (small / large) proteins, ranging from ___ to ___ KD

small; 10 - 30

Cytokines are secreted proteins, meaning ….

they are produced in the cytoplasmic area and released into the extracellular space

What are the two groups of intracellular proteins?

1. free proteins - for cell signaling (monomers, dimers, trimers)

   1. ex. kinases, receptors, G-proteins

2. structural proteins - deployed into structures like the cytoskeleton

   1. ex. microtubule, actin, myosin, etc

____, ____, and _____ (cell types) can produce or express cytokines.

leukocytes (white blood cells); vascular cells; fibroblasts

What are the different types of cytokines?

1. interleukins

2. interferons

3. chemokines

4. transforming growth factors

5. tumor necrosis factors

6. stem cel factors * (not as relevant)

cytokines and growth factors are responsible for stimulating cell ____ and cell _____.

protection and regeneration

How are cytokines and growth factors different?

1. sources that produce them

2. structure

Growth factors are mostly produced by _____, like ____ and ____.

non blood cels like vascular cells and fibroblasts

What are the types of growth factors?

1. neurotrophic GFs (brain-derived)

2. platelet derived GF

3. epidermal GF

4. insulin - like GF

What are the two forms of cell regeneration?

1. cell proliferation

2. cell regeneration

what is cell proliferation?

formation of cells identical to the mother cell in phenotype (morphology, structure, and function)

what is cell regeneration?

the formation of cells different from mother cells in phenotype (differentiation)

regardless of different phenotypes, all cells generally have the same _____.

genotype

what do supporting processes do?

processes not directly involved in cell division / proliferation/ differentiation / regeneration

indirectly provide a way or means to speed up or inhibit cell regeneration

what are the 7 supporting processes/responses to insult? Also include the time it takes from injury to trigger these processes.

1. endothelial cell permeability increase (min - days)

2. cytokine release → chemokine (hours - days)

3. leukocyte infiltration → cytokines

4. GF expression protein production increase (one day - multiple days)

5. cell regeneration (mitosis) (3-5 days)

6. Angiogenesis (blood cell formation) (days - weeks)

7. fibrosis → fibroblasts (days - months)

what is vascular permeability?

the ability of molecules to go in through the endothelial layer

what is the unit for permeability?

level of molecules going through membrane at unit length per unit time

when injury occurs _____ release histamines

mast cells

histamines act on endothelial cells to cause ______.

contractions; opens the gap junctions between the endothelial cells

why does endothelial cell permeability need to be increased in response to injury?

to bring all protective and regenerative molecules from the blood and non-injured organs to the injured organs

what do chemokines do?

bring leukocytes to the site of injury

_____ are the major cell type that undergoes mass regeneration

fibroblasts

What are the two functions of fibroblasts?

to produce:

1. growth factors

2. extracellular matrix (collagen)

Matrix production is typically excessive, leading to the formation of ______.

scar tissue

During left ventricular myocardial tissue death, collagen regeneration is required to …

strengthen the wall to increase mechanical strength and toughness

to prevent cardiac rupture

What is the rationale for the necessity of regenerative engineering?

1. inadequate timing of regenerative processes

   1. ex. heart attack causes cell death in mins to hours, but regeneration takes 5 days

2. suboptimal effectiveness of cellular regenerative processes

what is etiology?

causes of human disease

What is pathogenesis?

the study of how a human disease develops/ mechanisms of disease

what is pathology?

the study of the changes in structure of molecules cells, and organs

what is pathophysiology?

the study of the changes in functions of molecules, cells, and organs

What is the order of how to study disease (the -ologies)?

1. etiology

2. pathogenesis

3. pathology

4. pathophysiology

How does a disease occur / what are the etiological factors?

1. environmental insults

2. genetic defects

3. senescence (aging)

What are the two subclasses of environmental insults?

1. external - from our environment

2. internal - within the human body

What are external environmental insults?

1. microorganisms

   1. viruses

   2. bacteria

   3. fungi

   4. parasites — some may be larger than the micro level

2. toxins

3. mechanical impacts and penetrations

4. hypoxia (Oxygen level drop)

   1. Ischemia- blood flow perfusion deficiency (internal caused by external)

5. radiation

6. temperature

7. over-nutrition

_____ causes most of heart attack-induced cardiac arrest or human death

hypoxia

What are the internal environmental insults?

1. oxidants

   1. superoxide (O2-) from ATP production

      1. the more we eat (over nutrition) more superoxide is produced

   2. Reactive Oxygen Species (ROS)

      1. Nitric Oxide (NO)

2. pressure (fluid / solid)

3. fluid shear stress (Force / Area = N/m²)

What are can superoxide do?

image DNA, gene mutations, RNA damage, protein damage, etc

____, ____, and ____ are very sensitive to superoxide.

neurons, cardiomyocytes, pancreatic beta cells

hypertension is increase in _____.

blood pressure

What is fluid shear stress?

pressure between solid wall surface and fluid particles

shear stress units:

force/ Area = N/m²

endothelial cell injury causes ____

thrombosis → atherosclerosis

what is the effect of super high shear stress?

endothelial cell denudation (removal or loss of think leyer of ECs lining the vessels)

what is the effect of super low shear stress?

blood vessels become completely blocked by cell growth → similar to plaque formation (atherosclerosis)

The two different types of viruses are: ___ and ___

RNA and DNA

How do RNA virsuses replicate?

by inserting themselves into host cell genome

what is the definition of a virus?

a small structure / particle that can infect host cells and replicate in host cells to survive causing human disorder by causing cell injury and death

True / False: all RNA viruses cause human disease

False — only a fraction of RNA viruses actually cause human disease

What are different forms of RNA viruses?

1. single-stranded RNA

   1. 1 copy of RNA

   2. 2 copies of RNA — retrovirus

2. Double-stranded RNA

   1. rotaviruses

What are some examples of single-stranded RNA viruses?

ebola, polio, hep. A, covid

Positive sense single-stranded RNA genome has the RNA sequence that can be directly translated into ____

proteins

Sense vs. Anti-sense RNA strands in human cells?

• sense (the coding strand) — DNA has the same sequence as the mRNA

• anti-sense — the complementary DNA strand that RNA polymerase uses as a template to synthesize the mRNA

human leukocytes and bone marrow cells have specific receptors that make them easily infected by _____.

HIV

influenze viruses have __ copies of single strand RNA virus

8

Rotaviruses affect cells in the ____.

GI track

What do capsid proteins do?

interact with host cell receptors to trigger endocytosis

What are the 3 steps of endocytosis?

1. binding of virus + specific receptor

2. form a dip in the cell membrane that will enclose virus + receptor

3. dip / pocket is pinched off - forming an independent endosome

4. endosome will be ruptured and released into the genome

The _____is the core of an RNA virus

genome

core proteins and enzymes _____ the genome.

organize the genome - put DNA and RNA in order

retroviruses have _____ responsible for replicating the RNA genome

RNA-dependent RNA polymerases

____ is a protein based case that encloses the genomic core of an RNA virus

capsid

the external membrane of an RNA virus is called an ____

envelope

Two common retroviruses are ____ and ____

HIV and Lentivirus

in retroviruses _______ is responsible for the reverse transcription of RNA genome to DNA genome to make _____

reverse transcriptase; to make cDNA (copy DNA)

_____ is the enzyme that can grab viral cDNA pieces and integrate it in the host genome

integrase

What are the two necessary conditions for integrase to integrate cDNA into viral protein?

• double-stranded break in the host genome

• host cell division, so viral cDNA can be integrated in the newly produced genome

What are the key functions of RNA viruses?

1. host cell infection

   1. Receptors are key

2. replication

   1. RNA-dependent RNA polymerase-containing RNA viruses

   2. retroviruses use reverse transcriptase

Coronaviruses affect what kind of cells?

• epithelial cells in lungs

• cardiomyocytes

• muscular cells

_____ is the the strategic manipulation and hijacking of host cellular machinery, processes, and resources by viruses to facilitate their own entry, replication, assembly, and evasion of immune responses.

exploitation

HIV cells affect _____.

leukocytes

Coronavirus receptor can directly react with _____.

ACE - angiotensen converting factor

What is the primary function of ACE?

cleaves angiotensen 1 → ang 2 to increase smooth muscle contration + increase BP

True / False: single celled organisms don’t have ACE

True — no need for ACE

What are the two theories for the formation of the ACE receptor?

1. hijacking theory existing receptors for viruses

2. viral infection was the driving force

Human cells only have ____-dependent RNA polymerases

DNA

When a virus invades the host cells into the ____, they dis-assemble

cytosol

All viruses can only survive in host cells because…

there are no components for the replication of virsuses (nucleotides, protein translation enzymes, energy) within the blood or extracellular space

newly made viral particles can be released from the host cell via ____

exocytosis

All retroviruses have ___ and ___ to allow their replication

reverse transcriptase and integrase

______ is used to convert RNA to cDNA

reverse transcriptase

When there is a double strand break, _____ inserts cDNA into the host cell DNA

integrase

What are the 5 key pathogenic mechanisms in which RNA viruses cause human diseases?

1. toxins

2. competing for machineries and enzymes for protein translation + RNA transcription

3. competing for nutrients

4. physical interference

5. adverse impact of inflammation

Toxins cause cell death by binding to host cell molecules and intefere host cell _____ function

protein

What are the 2 primary adverse effects of inflammation

1. increased EC permeability → edema

2. fibrosis

____ is water accumulation in extracellular space

edema