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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

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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

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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

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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

Comment by Dr. Krishna Kumari Challa on May 6, 2023 at 12:57pm

The average age of participants was 54 years, 62% were women and 88% were mobile phone users. During a median follow up of 12 years, 13,984 (7%) participants developed hypertension. Mobile phone users had a 7% higher risk of hypertension compared with non-users. Those who talked on their mobile for 30 minutes or more per week had a 12% greater likelihood of new-onset high blood pressure than participants who spent less than 30 minutes on phone calls. The results were similar for women and men.

Looking at the findings in more detail, compared to participants who spent less than 5 minutes per week making or receiving mobile phone calls, weekly usage time of 30-59 minutes, 1-3 hours, 4-6 hours and more than 6 hours was associated with an 8%, 13%, 16% and 25% raised risk of high blood pressure, respectively. Among mobile phone users, years of use and employing a hands-free device/speakerphone were not significantly related to the development of hypertension.

The researchers also examined the relationship between usage time (less than 30 minutes vs. 30 minutes or more) and new-onset hypertension according to whether participants had a low, intermediate or high genetic risk of developing hypertension. Genetic risk was determined using data in the UK Biobank.

The analysis showed that the likelihood of developing high BP was greatest in those with high genetic risk who spent at least 30 minutes a week talking on a mobile—they had a 33% higher likelihood of hypertension compared to those with low genetic risk who spent less than 30 minutes a week on the phone.

These  findings suggest that talking on a mobile may not affect the risk of developing high BP as long as weekly call time is kept below half an hour. More research is required to replicate the results, but until then it seems prudent to keep mobile phone calls to a minimum to preserve heart health.

Ye Z, Zhang Y, Zhang Y, et al, Mobile phone calls, genetic susceptibility and new-onset hypertension: results from 212,046 UK Biobank participants, European Heart Journal—Digital Health (2023). DOI: 10.1093/ehjdh/ztad024.

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Part 2

Comment by Dr. Krishna Kumari Challa on May 6, 2023 at 12:55pm

Mobile phone calls linked with increased risk of high blood pressure

Talking on a mobile for 30 minutes or more per week is linked with a 12% increased risk of high blood pressure compared with less than 30 minutes, according to research published recently in European Heart Journal—Digital Health.

It's the number of minutes people spend talking on a mobile that matter for heart health, with more minutes meaning greater risk.

Almost three-quarters of the global population aged 10 and over own a mobile phone. Nearly 1.3 billion adults aged 30 to 79 years worldwide have high blood pressure (hypertension). Hypertension is a major risk factor for heart attack and stroke and a leading cause of premature death globally.

Mobile phones emit low levels of radiofrequency energy, which has been linked with rises in blood pressure after short-term exposure. Results of previous studies on mobile phone use and blood pressure were inconsistent, potentially because they included calls, texts, gaming, and so on.

This study examined the relationship between making and receiving phone calls and new-onset hypertension. The study used data from the UK Biobank. A total of 212,046 adults aged 37 to 73 years without hypertension were included. Information on the use of a mobile phone to make and receive calls was collected through a self-reported touchscreen questionnaire at baseline, including years of use, hours per week, and using a hands-free device/speakerphone.

Participants who used a mobile phone at least once a week to make or receive calls were defined as mobile phone users.

The researchers analyzed the relationship between mobile phone usage and new-onset hypertension after adjusting for age, sex, body mass index, race, deprivation, family history of hypertension, education, smoking status, blood pressure, blood lipids, inflammation, blood glucose, kidney function and use of medications to lower cholesterol or blood glucose levels.

Part 1

Comment by Dr. Krishna Kumari Challa on May 6, 2023 at 12:51pm

Fruit fly gut research leads to discovery of new phosphate-storing organelle

Scientists  have discovered something remarkable while studying phosphate transport in fruit fly intestines—a never before seen organelle. Their results are published in the journal Nature, and a News and Views piece in the same journal discusses their findings.

Organelles are the structures performing specific functions within the cell and form the basis for most introductory biology courses. Major organelles include the nucleus, where DNA is kept and translated into RNA; the endoplasmic reticulum, where RNA is translated into proteins; and the Golgi apparatus, where enzymatic processing of proteins takes place; and the mitochondrion, which powers the cell and is involved in monitoring and regulating the cell as well as some intercellular communication.

A few dozen other minor organelles exist within animal cells, and it might have been assumed that every organelle had been discovered after so many years of research. But not so, as detailed in the researchers' new paper, "A phosphate-sensing organelle regulates phosphate and tissue homeostasis."

Immunostaining and ultrastructural analyses showed that PXo specifically appeared in a previously unknown multilamellar membrane—a newly discovered organelle the researchers named PXo bodies. The PXo was essentially storing phosphate in the PXo bodies. When PXo was downregulated or missing, the PXo bodies degraded, releasing the backup storage of phosphate into the cell.

Future investigations will be required to map this new organelle's full functions and interactions and could search for PXo bodies in other life forms.

 Chiwei Xu et al, A phosphate-sensing organelle regulates phosphate and tissue homeostasis, Nature (2023). DOI: 10.1038/s41586-023-06039-y

Emily Strachan et al, Phosphate-storing organelle discovered in fruit flies, Nature (2023). DOI: 10.1038/d41586-023-01410-5

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