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Comment by Dr. Krishna Kumari Challa on May 7, 2023 at 11:00am

The Human Digestive System Varies a lot from person to person

The human digestive system is much more variable than we tend to think, according to a new study, with significant differences in gut anatomy even among healthy individuals.

This includes individual differences from person to person, the researchers report, plus broader differences such as those between women and men.

In one noteworthy example, the researchers found that women tend to have longer small intestines than men, by an average of 30.7 centimeters.

Because having a longer small intestine helps you extract nutrients from your diet, this finding supports the canalization hypothesis, which posits that women are better able to survive during periods of stress.

The study also revealed more granular differences, suggesting healthy human digestive systems are far more variable than many experts had appreciated.

If you're talking to four different people, odds are good that all of them have different guts, in terms of the relative sizes of the organs that make up that system.

For example, the cecum is an organ that's found at the nexus of the large and small intestine[s]. One person may have a cecum that is only a few centimeters long, while another may have a cecum the size of a coin purse.

The researchers point out that this has big implications for health care, emphasizing the importance of recognizing individual differences in gastrointestinal systems rather than focusing on typical or "normal" anatomy among humans in general.

The researchers point out, however, that humans stand apart for our high variation in intestinal length compared with other species. One possible explanation, they suggest, is that humans don't eat a "standardized captive diet," unlike many other species .

https://peerj.com/articles/15148/

Comment by Dr. Krishna Kumari Challa on May 7, 2023 at 10:52am

9. W. Huang et al., "Cellular senescence: the good, the bad and the unknown," Nat Rev Nephrol, 18(10):611-27, 2022. 

10. D. McHugh, J. Gil, "Senescence and aging: causes, consequences, and therapeutic avenues," J Cell Biol, 217(1):65-77, 2018.  

11. R. Di Micco et al., "Cellular senescence in ageing: from mechanisms to therapeutic opportunities," Nat Rev Mol Cell Biol, 22(2):75-95, 2021.

12. J. Yang et al., "The paradoxical role of cellular senescence in cancer," Front Cell Devl Biol, 9, 2021. 

13. F. Hernandez-Gonzalez et al., "Cellular senescence in lung fibrosis," Int J Mol Sci, 22(13):7012, 2021. 

14. A.K. Palmer et al., "Senolytics: potential for alleviating diabetes and its complications," Endocrinology, 162(8):bqab058, 2021. 

15. D. Beaulieu et al., "Phospholipase A2 receptor 1 promotes lung cell senescence and emphysema in obstructive lung disease. Euro Respir J, 2021. 

Part 5

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Comment by Dr. Krishna Kumari Challa on May 7, 2023 at 10:51am

Footnotes:

 J. Park et al., "Promotion of intestinal epithelial cell turnover by commensal bacteria: role of short-chain fatty acids," PLoS ONE, 11(5):e0156334, 2016. 

2. L. Ottoboni et al., "Therapeutic plasticity of neural stem cells," Front Neurol, 11, 2020.  

3. L. Hayflick, P.S. Moorhead, "The serial cultivation of human diploid cell strains," Exp Cell Res, 25(3):585-621, 1961.

4. Kumari R, Jat P. "Mechanisms of cellular senescence: cell cycle arrest and senescence associated secretory phenotype," Front Cell Dev Biol, 2021.

5. V. Gorgoulis et al., "Cellular senescence: defining a path forward," Cell, 179(4):813-27, 2019.  

6. N.S. Gasek et al., "Strategies for targeting senescent cells in human disease," Nat Aging, 1(10):870-79, 2021. 

7. S. Da Silva-Álvarez et al., "The development of cell senescence," Exp Gerontol, 128:110742, 2019. 

8. M. Storer et al., "Senescence Is a developmental mechanism that contributes to embryonic growth and patterning," Cell, 155(5):1119-30, 2013.  

Part 4

Comment by Dr. Krishna Kumari Challa on May 7, 2023 at 10:51am

Anti-senescent Treatments

Researchers have developed drugs called senolytics to selectively target senescent cells that are resistant to apoptosis. These drugs work by upregulating antiapoptotic pathways.⁶ Eliminating these cells is important in diseases such as fibrosis (e.g., pulmonary fibrosis), where tissue is scarred and thickened.¹³ Additionally, patients with obesity or diabetes have high levels of senescent cells in adipose tissue, which contributes to fat cell size.¹⁴ For pulmonary fibrosis and diabetic kidney disease, researchers have conducted clinical trials testing senolytics and observed promising results.⁶

Another class of drugs called senomorphics inhibits SASP.⁶ Reducing SASP is critical for preventing the spread of senescence to neighboring cells or tissues. For example, ruxolitinib reduces inflammation by inhibiting Janus kinases (JAKs), proteins involved in cytokine production.⁹ This drug was shown to be an effective treatment in a chronic obstructive pulmonary disease mouse model.¹⁵

^{Part 3}

Comment by Dr. Krishna Kumari Challa on May 7, 2023 at 10:51am

What Triggers Cell Senescence? 
Cell senescence is triggered by a variety of internal or external cellular insults. Examples of internal stresses leading to senescence include shortening of the telomeres, DNA damage, mitochondrial dysfunction, nutrient deprivation, oncogenic pathway activation.⁴ Some examples of external stresses are radiation and chemotherapeutic agents.⁴  

Senescence-Associated Secretory Phenotype 
A major characteristic of senescent cells is the senescence-associated secretory phenotype or SASP.¹⁰ SASP encompasses a senescent cell’s secreted components, or secretome, and includes pro-inflammatory cytokines, chemokines, proteases, growth factors, reactive oxygen species (ROS), and extracellular matrix proteins.¹⁰ Senescent cells use these metabolically active components to communicate with surrounding cells and change the environment in either a positive or negative manner. For instance, SASP can recruit immune cells to remove senescent cells, remodel tissue by secreting angiogenic factors, or promote senescence in other cells through paracrine signalling.¹⁰

Senescence and Aging 

Senescence is an important contributor to aging as it depletes various cell pools, including progenitor and stem cells that can replace damaged tissue over time.¹¹ The SASP of senescent cells enhances inflammation, which increases susceptibility to many age-related diseases, such as heart disease, diabetes, and cancer.¹¹ SASP-mediated paracrine signaling can also encourage neighboring cells to undergo senescence.¹¹

Senescence and Cancer 

A major hallmark of cancer progression is cell proliferation.³ As such, researchers previously thought that the senescence pathway suppressed tumors as it eliminated proliferative cells.¹² However, there is increasing evidence that the SASP may contribute to cancer progression by creating an immunosuppressive environment.¹²

^{Part 2}

Comment by Dr. Krishna Kumari Challa on May 7, 2023 at 10:50am

Cell Senescence

Each cell in an organism has an average life span. For example, cells lining the surface of the human gut or skin typically live 3-5 days before they die.¹ In contrast, stem cells and neurons can survive for many years.² The process by which a cell arrests their growth after completing its life span is called cell senescence.  

Cell senescence is the expression of aging at the cellular level, and the phenomenon occurs when a cell stops dividing and arrests in the G1 phase of the cell cycle.^3,4 During this phase, the cell undergoes numerous phenotypic and metabolic changes. Some of these phenotypic changes include chromatin remodeling with global demethylation and heterochromatin foci formation, which alters the cell’s gene expression landscape.⁵ Additionally, senescent cells are larger in size and more granular.⁶ Senescent cells are eradicated from the body either through apoptosis or by immune cells such as macrophages.⁵

Although cell senescence is often associated with aging, it is an important process during embryogenesis, wound healing, and maintaining homeostasis.⁷ For instance, during central nervous system development, parts of the neural tube undergo senescence for proper formation of the brain and spinal cord.⁸

Cell senescence was first identified by Leonard Hayflick and Paul Moorhead in 1961, when they serially passaged human fibroblast cells in culture.³ They noticed that the cells stopped dividing after 40-60 passages. The number of cell divisions before cell cycle arrest is now known as the Hayflick limit.³

To detect senescent cells in the laboratory, researchers use markers such as senescence-associated B-galactosidase (SABG), which exists in the lysosome of these cells.⁹

^{Part 1}

Comment by Dr. Krishna Kumari Challa on May 7, 2023 at 10:44am

Mechanical Force on the Skull May Aid Bone Regeneration

By mechanically inducing the expansion of cranial sutures in young adult mice, researchers stimulated stem cell proliferation that is key to healing bone injuries.

Treatments available to repair damage to the skull as a result of trauma, surgery, or congenital anomalies are limited and sometimes involve risks. A study recently published in PNAS (1) offers an alternative approach inspired by how babies regenerate bone tissue. The researchers expanded on previous studies (2,3) showing that open sutures—the fibrous connective tissue holding bones together—in the skulls of newborn mice and humans are reservoirs of skeletal stem cells. The temporary mechanically-induced expansion of closed sutures in young adult mice resulted in the proliferation of skeletal stem cells and facilitated bone regeneration following an injury.

A major contribution of this study is that it advances our knowledge about the impact of external forces on the structure of cranial sutures and the potential healing properties of such impact.

Researchers first compared the cell composition of the calvarial suture—which joins the bilateral bones in the roof of the skull—in mice of different ages and found that the number of skeletal stem cells is significantly reduced in older mice compared to younger mice. Increased numbers of stem cells correlate with open sutures in newborns, leading them to wonder whether expanding the sutures in adults would increase the number of stem cells enough to harness their regenerative potential.

The team achieved this goal in 2-month-old mice, which the researchers considered the equivalent of young adults in humans. When the researchers mechanically induced calvarial suture expansion, the number of skeletal stem cells increased significantly. Moreover, mice that received an injury to the skull near the suture simultaneous to the mechanical expansion exhibited near complete bone regeneration after 60 days, something that was not achieved in control mice without the expansion device. This mechanically-induced regeneration did not occur in 10-month-old mice, probably due to the limited supply of preexisting skeletal stem cells in the sutures, which is insufficient to achieve successful proliferation.

Finally, the team showed that suture stem cell proliferation and the resulting healing effects depend on Wnt signaling, a pathway that regulates key aspects of animal development.

1. Aldawood, Z.A. et al. (2023) “Expansion of the sagittal suture induces proliferation of skeletal stem cells and sustains endogenous calvarial bone regeneration,” Proceedings of the National Academy of Sciences

2. Zhao, H. et al. (2015) “The suture provides a niche for mesenchymal stem cells of Craniofacial Bones,” Nature Cell Biology, 17(4), pp. 386–396. Available at: https://doi.org/10.1038/ncb3139.

3. Maruyama, T. et al. (2016) “Stem cells of the suture mesenchyme in craniofacial bone development, repair and Regeneration,” Nature Communications, 7(1). Available at: https://doi.org/10.1038/ncomms10526.

Comment by Dr. Krishna Kumari Challa on May 6, 2023 at 1:24pm

Stroke: Know the signs and risk factors

To recognize the signs of stroke, remember the acronym FAST:

• Face: Does the face droop on one side when the person tries to smile?
• Arms: Is one arm lower when the person tries to raise both arms?
• Speech: Can the person repeat a simple sentence? Is speech slurred or hard to understand?
• Time: During a stroke, every minute counts. If you observe any of these signs, call 911 or your local emergency number immediately.

Risk factors

Many factors can increase the risk of stroke, including:

• Age: People 55 or older have a higher risk of stroke than younger people.
• Race or ethnicity: People who are African American and Hispanic have a higher risk of stroke than people of other races or ethnicities.
• Sex: Men have a higher risk of stroke than women. Women are usually older when they have strokes, and they're more likely to die of strokes than men, however.
• Hormones: Use of birth control pills or hormone therapies that include estrogen increases risk.

Potentially treatable stroke risk factors include lifestyle and medical factors.

Lifestyle risk factors include:

• Being overweight or obese
• Physical inactivity
• Heavy or binge drinking
• Use of illegal drugs, such as cocaine and methamphetamine

Medical risk factors include:

• High blood pressure
• Cigarette smoking or secondhand smoke exposure
• High cholesterol
• Diabetes
• Obstructive sleep apnea
• Cardiovascular disease, including heart failure, heart defects, heart infection or irregular heart rhythm
• Personal or family history of stroke, heart attack or transient ischemic attack
• COVID-19 infection

Comment by Dr. Krishna Kumari Challa on May 6, 2023 at 1:15pm

Treatment for uterine fibroids without surgery

A newer, more effective treatment for uterine fibroids is available that doesn't require surgery.

Dr. Elizabeth Stewart, a Mayo Clinic gynecologist and researcher, recently published a review on these approved fibroid medications. They are called oral gonadotropin-releasing hormone (GnRH) antagonist combinations.

There are two new FDA-approved drugs for the medical treatment of uterine fibroids.  The drugs are effective in treating heavy menstrual bleeding, relieving pain and reducing the need for a hysterectomy.

Because many women are pushed in the direction of surgical therapy, and we know there are big limitations to surgical therapies, this is a great treatment option for many women.

Fibroids are benign growths in the uterus. While common, they can be disruptive.

And disproportionally affect women of color.

These medicines block the body from making the hormones that cause women to ovulate and have their periods. The medicines don't eliminate your fibroids but they do reduce their size. The FDA has approved the use of these oral therapies for up to two years.

Common symptoms include:

• Heavy menstrual bleeding.
• Menstrual periods lasting more than a week.
• Pelvic pressure or pain.
• Pain during sex.
• Frequent urination.

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Vaginal electrical stimulation, TTNS both effective for overactive bladder

Short-term interventions of vaginal electrical stimulation (VS) and transcutaneous tibial nerve electrical stimulation (TTNS) are effective for treating overactive bladder syndrome (OAB) in women, according to a study published online April 12 in Neurourology & Urodynamics.

Janaina Mayer de Oliveira Nunes et al, Transcutaneous tibial nerve electrical stimulation versus vaginal electrical stimulation in women with overactive bladder syndrome: Is there a role for short‐term interventions?, Neurourology and Urodynamics (2023). DOI: 10.1002/nau.25179

Comment by Dr. Krishna Kumari Challa on May 6, 2023 at 1:05pm

Can fish catch colds?

The simple answer to the question of whether fish can catch a cold is: no. This is because fish don't have lungs or a respiratory tract—or a nose to breathe through, for that matter. This is why you'll never see a fish with a hacking cough or a runny nose.

This isn't to say that fish cannot get ill, of course. "Fish—as well as bivalves such as mussels and oysters and crustaceans such as shrimp—exchange oxygen and CO2through their gills.

Waterborne viruses have evolved to attack the gills in the same way as airborne viruses have evolved to attack the lungs.

Gills are coated with a kind of mucus that acts as a kind of protective barrier. When this mucus is disrupted, this can create openings for viruses to infect the animal. You wouldn't define this infection as a cough or a sneeze, though.

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Researchers discover a potential cause of Parkinson's disease

In 2021, Professor Per Saris's group published results demonstrating that bacteria of the Desulfovibrio bacterial genus correlate with Parkinson's disease, and that their higher number also correlates with the severity of the symptoms of the disease. Replicating the same study, Chinese researchers came to the same conclusion.

The findings indicate that specific strains of Desulfovibrio bacteria are likely to cause Parkinson's disease. The disease is primarily caused by environmental factors, that is, environmental exposure to the Desulfovibrio bacterial strains that cause Parkinson's disease. Only a small share, or roughly 10%, of Parkinson's disease is caused by individual genes.Vy A. Huynh et al, Desulfovibrio bacteria enhance alpha-synuclein aggregation in a Caenorhabditis elegans model of Parkinson's disease, Frontiers in Cellular and Infection Microbiology (2023). DOI: 10.3389/fcimb.2023.1181315

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