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Potassium-Rich Foods May Boost Women’s Heart Health, Study Says

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Every gram of potassium consumed can lower systolic blood pressure by 2.4 mmHg.

preview for 5 Ways to Keep Your Heart Healthy
  • A new study found eating a potassium-rich diet may improve heart health, specifically for women with high sodium intake.
  • Researchers found for every gram of potassium consumed daily, systolic blood pressure was lowered by 2.4 mmHg.
  • Experts suggest incorporating more potassium-rich foods into your diet, like bananas, potatoes, beans, and spinach.

Researchers have known for a while that a diet high in potassium can help lower blood pressure and risk for cardiovascular disease, but a new study published in the European Heart Journal found that a potassium-rich diet can specifically help women improve their heart health.

The new study determined that the more grams of potassium consumed per day, the more the blood pressure of women who consumed high amounts of sodium improved. In fact, scientists found that for each additional gram of potassium consumed daily, systolic blood pressure was lowered by 2.4 mmHg. In short: as potassium levels went up in the diet, sodium levels went down in the blood.

The research examined how potassium impacted the blood pressure of nearly 25,000 participants. Of those in the study, about 55% were women and 45% were men and their data came from the European Prospective Investigation into Cancer-Norfolk study. Participants were from the United Kingdom and between the ages of 40 to 79 years old from 1993 to 1997.

Participants filled out a lifestyle questionnaire and had their blood pressure taken and urine sampled by researchers. Urine samples were examined for sodium and potassium levels. But the benefits weren’t just seen in women. Researchers followed up with participants after a median of 20 years and found that women who had the highest intake of potassium had an 11% lower risk of hospitalization or death due to cardiovascular disease and men lowered their risk by 7% compared to those with the lowest potassium intake.

What experts have to say

Howard Weintraub, M.D., cardiologist and clinical director of the Center for the Prevention of Cardiovascular Disease at NYU Langone Health says that the idea of potassium lowering the risk for cardiovascular disease and improving heart health and blood pressure isn’t anything new. What makes this study so impressive is that it included a huge cohort and they found a very significant change through their data, especially in women, he says.

Dr. Weintraub notes that the main limitation in this study, which the authors recognize, is that only one urine sample was collected per participant. He notes that sodium and potassium in the urine can fluctuate. For example, if you ate a plant-based meal with very limited salt versus a takeout hamburger with salty fries, it can impact the total amount of sodium and potassium in your urine.

But the main question experts still have is—why women? The study found the strongest association between lowering blood pressure and an increase in potassium intake for women who consumed high amounts of sodium. They did not find the same for men, and experts are still scratching their heads.

“It’s thought-provoking and hypothesis-provoking, but the fact that it has this unusual, more restricted relationship raises questions in my mind,” Dr. Weintraub says. He notes that the study authors offer a few ideas as to why this is, but the bottom line is that they don’t really know.

In the study, experts reference research done on rats where the female sex hormone (estrogen) likely played a part in the role of potassium in their overall health. But, studies on rats don’t always equate to human circumstances, Dr. Weintraub says. Additionally, the researchers note that many of the women involved in the study were postmenopausal, so other mechanisms may be playing a role in this case.

The bottom line

Cardiovascular disease is the leading cause of death worldwide, causing one in four deaths in men and one in five deaths in women in the United States, according to the Centers for Disease Control and Prevention. Risk factors for cardiovascular disease are high blood pressure, high cholesterol, and smoking. Additionally, many experts point to a diet high in sodium and processed foods as risk factors for cardiovascular disease.

This particular study suggests that eating more potassium can help the kidneys get rid of sodium in the blood, which can help blood pressure go down. If you can maintain lower blood pressure long-term, there can be a change in cardiovascular risk, Dr. Weintraub says.

“As a prevention specialist in the cardiovascular arena, we’ve always talked about limiting sodium intake, that has been an unambiguous issue,” he says. “The diet we encourage is the Mediterranean diet, which has been shown to save lives.”

If you’re looking for ways to lower your blood pressure naturally, it’s important to talk to your healthcare provider about the possible causes of your high blood pressure to create a plan that works for you. A diet that incorporates foods that help lower blood pressure naturally, can be key in realizing your target numbers.

Research has shown eating a wider variety of proteins may lower the risk of high blood pressure. Additionally, high-potassium foods can be an integral part of your diet plan, like white and sweet potatoes, bananas, beets, spinach, beans, and avocado.

Lastly, Dr. Weintraub warns to be cautious of consuming too much potassium in your diet, because it can impact kidney function and become very dangerous.

So, it’s important to consult your doctor before drastically increasing your potassium intake. And, these findings mean that adding a bit more into your routine could prove beneficial to heart health.

Rusfertide, a Hepcidin Mimetic, for Control of Erythrocytosis in Polycythemia Vera

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Abstract

Background

Polycythemia vera is a chronic myeloproliferative neoplasm characterized by erythrocytosis. Rusfertide, an injectable peptide mimetic of the master iron regulatory hormone hepcidin, restricts the availability of iron for erythropoiesis. The safety and efficacy of rusfertide in patients with phlebotomy-dependent polycythemia vera are unknown.

Methods

In part 1 of the international, phase 2 REVIVE trial, we enrolled patients in a 28-week dose-finding assessment of rusfertide. Part 2 was a double-blind, randomized withdrawal period in which we assigned patients, in a 1:1 ratio, to receive rusfertide or placebo for 12 weeks. The primary efficacy end point was a response, defined by hematocrit control, absence of phlebotomy, and completion of the trial regimen during part 2. Patient-reported outcomes were assessed by means of the modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) patient diary (scores range from 0 to 10, with higher scores indicating greater severity of symptoms).

Results

Seventy patients were enrolled in part 1 of the trial, and 59 were assigned to receive rusfertide (30 patients) or placebo (29 patients) in part 2. The estimated mean (±SD) number of phlebotomies per year was 8.7±2.9 during the 28 weeks before the first dose of rusfertide and 0.6±1.0 during part 1 (estimated difference, 8.1 phlebotomies per year). The mean maximum hematocrit was 44.5±2.2% during part 1 as compared with 50.0±5.8% during the 28 weeks before the first dose of rusfertide. During part 2, a response was observed in 60% of the patients who received rusfertide as compared with 17% of those who received placebo (P=0.002). Between baseline and the end of part 1, rusfertide treatment was associated with a decrease in individual symptom scores on the MPN-SAF in patients with moderate or severe symptoms at baseline. During parts 1 and 2, grade 3 adverse events occurred in 13% of the patients, and none of the patients had a grade 4 or 5 event. Injection-site reactions of grade 1 or 2 in severity were common.

Conclusions

In patients with polycythemia vera, rusfertide treatment was associated with a mean hematocrit of less than 45% during the 28-week dose-finding period, and the percentage of patients with a response during the 12-week randomized withdrawal period was greater with rusfertide than with placebo.

Virus-Like Protein May Explain Cancer-Induced Memory Loss

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Researchers at University of Utah Health have found that some tumors can release a protein that looks like a virus, kickstarting an out-of-control immune reaction that may damage brain cells, causing rapid-onset memory loss and cognitive deficits.

Jason Shepherd, PhD, associate professor of neurobiology at University of Utah Health and last author on the study, explains that the swift escalation of symptoms—which can include memory and behavioral changes, loss of coordination, and even seizures—is a hallmark of the disease, called anti-Ma2 paraneoplastic neurological syndrome. The disease is one of a group of cancer-related neurological syndromes that occur in less than one in 10,000 people with cancer. The precise symptoms of these diseases vary, but all involve rapid immune reactions against the nervous system. “The symptoms come in quickly and can be quite debilitating,” Shepherd says.

“This fascinating research illustrates how tumor cells can manipulate their environment,” says Neli Ulrich, PhD, executive director of the Comprehensive Cancer Center at Huntsman Cancer Institute at the University of Utah and a Jon M. and Karen Huntsman Presidential Professor in Cancer Research at the U. “We hope that this innovative transdisciplinary research will positively impact both the lives of cancer patients and of those who experience neurological symptoms.”

Stacey L. Clardy, MD, PhD, a neurologist at U of U Health and a coauthor on the study, adds, “Most patients begin to experience these unusual neurologic symptoms before they even know they have a cancer.”

These rapid-onset symptoms are the result of the immune system suddenly starting to target specific proteins that are found in the brain. Scientists knew that this flare of immunity often targets a protein called PNMA2. But nobody knew why PNMA2 provokes such a strong immune response, which left researchers at a loss for ways to prevent it. “We do not understand what is happening at the cellular or molecular level to actually cause the syndrome,” Clardy says, “and understanding the mechanism of disease is crucial to developing better treatments.”

To figure out how PNMA2 kickstarts an immune reaction, Junjie Xu, a graduate researcher in neurobiology at U of U Health and the lead author on the study, examined the protein’s structure using advanced microscopy. When he saw the first clear image of the protein, he was “so, so excited,” Xu says. Multiple PNMA2 proteins had spontaneously self-organized into 12-sided complexes that bore a striking resemblance to the geometric protein shells of some viruses.

One of the immune system’s healthy functions is to attack viruses, and PNMA2’s virus-like structure makes it particularly prone to being targeted as well, the researchers found. In fact, in experiments in mice, the immune system only attacked PNMA2 protein when it was assembled into virus-like complexes.

The location of PNMA2 in the body is also a crucial piece of the puzzle, the scientists found. “This protein normally is only expressed in the brain, in neurons,” Xu says, “but some cancer cells can express it, which can trigger an immune response.”

As long as PNMA2 stays in the brain, the immune system won’t react to it. But rarely, a tumor elsewhere in the body will start producing PNMA2 protein. And when the immune system detects PNMA2 protein outside the brain, it reacts like it would to any foreign invader. The immune system makes antibodies that bind to the unfamiliar substance, and those antibodies direct immune cells to attack.

But, once activated, the immune system doesn’t just attack the PNMA2 produced by the cancer. It also targets the parts of the brain that produce PNMA2 normally, including regions involved in memory, learning, and movement. The brain normally has a degree of protection from the immune system, but cancer weakens that barrier, leaving the brain especially vulnerable to this immune onslaught.

In future work, the researchers aim to figure out which aspect of the immune response leads to patients’ rapid cognitive decline—the antibodies themselves, immune cells making their way into the brain, or some combination of the two.

Understanding how the immune system causes neurological symptoms may help scientists design targeted treatments, Shepherd says. “If we show that PNMA2 antibodies are the culprit that really drives the neurological symptoms, you could devise a way to block those antibodies from getting into the brain or mop them up with something as a treatment… If you can alleviate some of those neurological symptoms, it really would be huge.”

Researchers Use Macrophage-Adhering Gadolinium Micropatches to Visualize mTBIs

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Researchers have created a new brain imaging method that allows mild traumatic brain injuries (mTBIs) to be diagnosed, even when existing imaging techniques like MRI don’t show any structural abnormalities. The technique involves loading gadolinium, a standard MRI contrast agent, into hydrogel-based micropatches that are attached to immune cells called macrophages. mTBIs cause inflammation in the brain, which produces signals that attract macrophages to migrate there. Coupling the gadolinium contrast agent to these cells enables MRI to reveal brain inflammation in a pig model of mTBI, which, in the future, could increase the number of correctly diagnosed TBI cases and improve patient care. The method is described in a paper published in Science Translational Medicine.

“70-90% of reported TBI cases are categorized as ‘mild,’ yet as many as 90% of mTBI cases go undiagnosed, even though their effects can last for years and they are known to increase the risk of a host of neurological disorders including depression, dementia, and Parkinson’s disease,” said senior author Samir Mitragotri, PhD, in whose lab the research was performed. “Our cell-based imaging approach exploits immune cells’ innate ability to travel into the brain in response to inflammation, enabling us to identify mTBIs that standard MRI imaging would miss.”

Mitragotri is a Core Faculty member of the Wyss Institute at Harvard University and the Hiller Professor of Bioengineering and Hansjörg Wyss Professor of Biologically Inspired Engineering at Harvard’s John A. Paulson School of Engineering and Applied Sciences (SEAS).

Because the effects of mTBI are believed to be caused by “invisible” brain inflammation, members of the Mitragotri lab decided to leverage their experience with immune cells to create a better diagnostic. “Our previous projects have focused on controlling the behavior of immune cells or using them to deliver drugs to a specific tissue. We wanted to exploit another innate ability of immune cells – homing to sites of inflammation in the body – to carry imaging agents into the brain, where they can provide a visible detection signal for mTBI,” said first author Lily Li-Wen Wang, PhD. Wang is a former Research Fellow in the Mitragotri Lab at the Wyss Institute and SEAS who is now a scientist at Landmark Bio.

The team planned to use their cellular backpack technology to attach gadolinium molecules to macrophages, a type of white blood cell that is known to infiltrate the brain in response to inflammation. But right away, they ran into a problem: in order to function as a contrast agent for MRI scans, gadolinium needs to interact with water. Their original backpack microparticles are compost of a polymer called PLGA, which is hydrophobic (meaning it repels water). So Wang and her co-authors started developing a new backpack made out of a hydrogel material that could be manufactured at a large scale in the lab.

After years of hard work, they finally created a new hydrogel backpack that could produce a strong gadolinium-mediated MRI signal, attach stably to both mouse and pig macrophages, and maintain their cargo for a sustained period of time in vitro. They named their new microparticles M-GLAMs, short for “macrophage-hitchhiking Gd(III)-Loaded Anisotropic Micropatches.” Now, it was time to test them in a more realistic setting, for which they partnered with researchers and clinicians at Boston Children’s Hospital.

First, they injected mouse M-GLAMs macrophages into mice to see if they could visualize them in vivo. They were especially interested to see if they accumulated in the kidney, as existing gadolinium-based contrast agents like Gadavist can cause health risks for patients with kidney disease. Their M-GLAMs did not accumulate in the mice’s kidneys, but persisted in their bodies for over 24 hours with no negative side effects. In contrast, mice injected with Gadavist® showed substantial accumulation of the contrast agent in their kidneys within 15 minutes of injection, and the substance was fully cleared from their bodies within 24 hours.

Then, they tested porcine M-GLAMs in a pig model of mTBI. They injected the M-GLAMs into the animals’ blood two days after a mock mTBI, then used MRI to evaluate the concentration of gadolinium in the brain. They focused on a small region called the choroid plexus, which is known as a major conduit of immune cells into the brain. Pigs that received the M-GLAMs displayed a significant increase in the intensity of gadolinium present in the choroid plexus, while those injected with Gadavist did not, despite confirmation of increased inflammation macrophage density in the brains of both groups. The animals showed no toxicity in any of their major organs following administration of the treatments.

“Another important aspect of our M-GLAMs is that we are able to achieve better imaging at a much lower dose of gadolinium than current contrast agents – 500-1000-fold lower in the case of Gadavist®,” said Wang. “This could allow the use of MRI for patients who are currently unable to tolerate existing contrast agents, including those who have existing kidney problems.”

The authors note that while M-GLAMs can indicate the presence of inflammation in the brain via the high concentration of macrophages entering it through the choroid plexus, their technique cannot pinpoint the exact location of injuries or inflammatory responses in brain tissue. However, if coupled with new treatment modalities like one they developed in another recently published paper, M-GLAMS could offer a more rapid and effective way to identify and reduce inflammation in mTBI patients to minimize damage and speed their recovery.

The researchers have submitted a patent application for their technology, and hope to be able to bring it to the market in the near future. They are currently exploring collaborations with biotech and pharmaceutical companies to accelerate it to clinical trials.

“This work demonstrates just how much potential is waiting to be unlocked within the human body for a variety of functions: monitoring health, diagnosing problems, treating diseases, and preventing their recurrence. I’m impressed with this team’s ingenuity in leveraging immune cells to improve medical imaging, and hope to see it in clinicians’ hands soon,” said Wyss Founding Director Donald Ingber, MD, PhD Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and the Hansjörg Wyss Professor of Bioinspired Engineering at SEAS.

EGFR Inhibitors for Lung Cancer Tied to Increased Keratitis Risk

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A close-up photo of an eye affected by keratitis.

Patients with lung cancer treated with epidermal growth factor receptor (EGFR) inhibitors may have an increased risk of new-onset keratitis, a U.S. population-based cohort study showed.

Over a 20-year period, 1.12% of patients who were treated with EGFR inhibitors developed new-onset keratitis compared with 0.74% of those who did not take these drugs (HR 1.520, 95% CI 1.339-1.725), reported Kevin Sheng-Kai Ma, DDS, of Harvard T.H. Chan School of Public Health in Boston, and colleagues in JAMA Ophthalmologyopens in a new tab or window.

Specifically, patients treated with EGFR inhibitors — including gefitinib (Iressa), erlotinib (Tarceva), afatinib (Gilotrif), and osimertinib (Tagrisso) — had higher risks of keratoconjunctivitis (HR 1.367, 95% CI 1.158-1.615), superficial keratitis (HR 1.635, 95% CI 1.306-2.047), and corneal ulcer (HR 2.132, 95% CI 1.515-3.002).

Notably, patients taking the second-generation EGFR inhibitor afatinib had the highest risk of keratitis (HR 2.229, 95% CI 1.480-3.356), though the risk was still observed with osimertinib, the standard first-line option in the metastatic setting (HR 1.591, 95% CI 1.130-2.239).

Ma told MedPage Today that clinicians should keep in mind that the drugs can significantly improve the overall survival of lung cancer patients. The findings “don’t tell us to stop EGFR inhibitors,” he said, “but would guide our clinical decisions in terms of whether or not we should follow the patients more frequently if the patients have shown early signs of severe forms of keratitis.”

According to the Cleveland Clinicopens in a new tab or window, contact lenses are a major risk factor for keratitis, and other risk factors include weakened immunity and long-term use of corticosteroids. Eye drops are initially prescribed, and corneal transplants may be needed in the most severe cases.

Jeanine Baqai, MD, of Northwestern University Feinberg School of Medicine in Chicago, told MedPage Today that eye doctors see keratitis often.

“It is important to decipher if the cause of this inflammation is infectious or non-infectious,” she said. “If there is concern for infection, we will typically culture the patient and start them on antimicrobial treatment. The infection may be bacterial, viral, fungal, or parasitic. If the inflammation is not felt to be infectious and there is no ulceration, we may treat with steroids. We are fortunate to be able to resolve most keratitis with topical treatment.”

EGFR inhibitors are used to treat several kinds of cancers including lung, breast, colorectal, and pancreatic cancer. Case reports and series have reported ocular adverse effects in patients taking the drugs for lung cancer, Ma noted, but no comprehensive studies have looked at the overall risk or stratified the results by type of drug and type of keratitis.

There are three generations of the drugs available, Ma said, and a fourth is under development. The risk remained steady over the 20-year period of the study, suggesting that the evolution of the drugs over time has not changed the risk level.

The drugs may boost the risk of keratitis by inhibiting healing within the cornea, Ma explained. “All patients taking all those drugs should be instructed by their ophthalmologist, medical oncologist, or primary care physicians about the potential complications from EGFR-targeted therapies.”

Baqai said the link between the drugs and keratitis “is certainly known amongst cornea subspecialists, but it is not a complication we typically see on a regular basis like other conditions.” However, “as more drugs surface, the prevalence with which we see these patients increases.”

“Cancer patients and patients receiving these medications should be examined and evaluated with a very discerning eye,” she added. “Sometimes we can see side effects from medications and other times we can see manifestations related to the cancer itself. It is important to be very thoughtful about the cause and the treatment of any keratitis, since the condition can lead to loss of vision. Expedited referral to the appropriate subspecialist is always recommended.”

For this study, Ma and team examined data from the TriNetX database on 1,388,108 adult patients who were treated for lung cancer from May 2003 through October 2023. The index dates were the date of first prescription for the patients who took the EGFR inhibitors or the date of diagnosis with lung cancer for the patients who did not take these drugs.

Of the total patients, 22,225 received EGFR inhibitors. Mean age was 69.7, and 62.8% were women. About half of patients in both groups had hypertensive diseases; those taking EGFR inhibitors were more likely to have secondary malignant neoplasms.

What’s next? Ma said his team is working on follow-up studies to examine the risk of keratitis by ethnicity, since research has linked ethnic background to EGFR mutation status.

Hubble Detects Uber-Strong Radio Transmission From Ancient “Blob”

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“It’s these types of environments — these weird ones — that are driving us toward better understanding the mystery of FRBs.”

On the Radio

The humble Hubble Space Telescope has been instrumental in observing something remarkable: the possible and highly unusual birthplace of the most distant fast radio burst (FRB), extremely powerful and unresolved flashes of radio frequency, ever observed.

The FRB was first discovered 18 months ago by the Australian Square Kilometre Array Pathfinder radio telescope.

Scientists were excited, if not stumped, by the super-strong energy burst — more than four times more energetic than other FRBs that have been detected — and subsequent observations revealed that it came from an extremely distant location, dating back to when the universe was just five billion years old.

When it was first detected, this radio burst seemed to originate near, as a press release describes it, “an unidentifiable, amorphous blob.” Early on, researchers speculated that the blob could be a group of up to three galaxies.

When Hubble took on the case, however, the FRB’s probable origin became clearer: a group of at least seven galaxies that existed when the Universe itself was only five billion years old — a highly unusual conclusion that could force us to reconsider what we know about the unusual phenomenon.

Explosive Interactions

The finding caught scientists studying the Hubble observations by surprise.

“It required Hubble’s keen sharpness and sensitivity to pinpoint exactly where the FRB came from,” said Northwestern graduate student Alexa Gordon, lead author of a recent study about the research, in the statement. “Without Hubble’s imaging, it would still remain a mystery as to whether this was originating from one monolithic galaxy or from some type of interacting system.”

Gordon and her colleagues also noted that there is a likelihood that the galaxies in question may be in the process of merging, which could contribute to the FRB’s strength.

“This interaction could trigger bursts of star formation,” Gordon said in the statement. “That might indicate that the progenitor of FRB 20220610A is associated with a fairly recent population of stars, which matches what we’ve learned from other FRBs.”

“Despite hundreds of FRB events discovered to date, only a fraction of those have been pinpointed to their host galaxies,” added study co-author and NSF graduate research fellow Yuxin Dong. “Within that small fraction, only a few came from a dense galactic environment, but none have ever been seen in such a compact group. So, its birthplace is truly rare.”

As one might imagine, FRBs are a persistent space enigma — and scientists who’ve worked on this discovery are hopeful that it will contribute to their understanding of how these strange transmissions work.

“It’s these types of environments — these weird ones — that are driving us toward better understanding the mystery of FRBs,” Gordon said.

Markedly divergent effects of Ouabain on a Temozolomide-resistant (T98G) vs. a Temozolomide-sensitive (LN229) Glioblastoma cell line

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Abstract

Background

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with poor prognosis. GMB are highly recurrent mainly because of radio- and chemoresistance. Radiotherapy with Temozolomide (TMZ) is until today the golden standard adjuvant therapy, however, the optimal treatment of recurrent glioblastoma remains controversial. Ouabain belongs to the Cardiotonic Steroids (CTS) the natural ligands of the Na/K-ATPase (NKA). It is established that the NKA represents a signal transducer with either stimulating or inhibiting cell growth, apoptosis, migration and angiogenesis. Over the last decade evidence grew that CTS have anti-tumor properties especially in GBM.

Discussion

The results show that with regard to cell migration as well as plasma cell membrane depolarization Ouabain indeed has different effects on the two GBM cell lines, the TMZ-sensitive LN229 and the TMZ-resistant T98G cell line, similar to the results found by the group of Chen and coworkers with respect to apoptosis [46]. The authors showed that in T98G cells apoptosis was induced at significantly lower Ouabain concentrations (0.1 μM) as compared to LN229 cells (> 1 µM). However, in our setting, LN229 cells did not show any reaction to Ouabain neither in the migration assay nor in the cell membrane potential assay, even at higher concentrations (> 10 µM). For this discrepancy we do not have a plausible explanation and further studies are needed.

In contrast, the TMZ-resistant cell line T98G showed a marked inhibition of migration at rather low doses of Ouabain (0.01–0.1 µM), which correlated significantly with an increase in cell membrane depolarization (p = 0.002). A similar opposite reaction pattern to Ouabain was observed in the LN229 and T98G cells in the Bcl-2 analysis i.e., only in the T98G cell line we saw a down-regulation whereas LN229 did not show any reaction. The fact, that the Bcl-2 down-regulation was detected only at very low Ouabain concentrations (0.01 nM) must be interpreted with caution, we will discuss this issue further down. In summary, while the TMZ-resistant T98G cell line is sensitive to Ouabain, the TMZ-sensitive LNN29 cell line seems to be resistant to Ouabain.

Interestingly, migrating GBM cells are per se resistant to apoptosis. Joy and coworkers revealed an activation of the phosphoinositide 3-kinase (PI3-K) survival pathway by migrating glioma cells, which renders them resistant to apoptosis [68]. Applying a specific inhibitor of PI3-K (LY294002) to migrating cells the phosphorylation of Akt was inhibited and consequently, an increased rate of apoptosis was seen. Yang and coworkers could demonstrate that Ouabain is able to prevent phosphorylation of Akt and mTOR, inhibiting cell migration and enhancing apoptosis [47]. Lefranc and coworkers also stressed the importance of an inverse relationship between migration and apoptosis in GBM and the key role of the PI3-K/Akt pathway [69].

The fact that the T98G cells reacted to the cell migration assay as well as to the plasma cell membrane potential assay at similar Ouabain concentrations strongly indicates a causal relationship between migration inhibition, depolarization of the cell membrane, and consequent induction of apoptosis.

Many authors described a correlation between plasma cell membrane (PCM) depolarization and early apoptosis, but it is not fully clear whether it constitutes a causal relationship or a mere epiphenomenon. There is evidence that PCM depolarization is a prerequisite for apoptosis. Suzuki-Karasaki and coworkers described the disruption of intracellular K + and Na + concentrations as a basic important event leading to depolarization, cell shrinkage, and hence apoptosis [70]. Bortner and coworkers reported in Jurkat T-cells a PCM depolarization immediately after application of diverse apoptotic stimuli (anti-Fas antibody, thapsigargin and the calcium ionophore A23187) followed by cell shrinkage [71]. Moreover, an early increase in intracellular Na + as well as inhibition of K + uptake was observed in response to anti-Fas, indicating an inactivation of the Na + /K + -ATPase. Interestingly, Ouabain enhanced anti-Fas-induced apoptosis. Finally, applying an anti-apoptotic signal, i.e., protein kinase C, did not only inhibit apoptosis but also prevent cell membrane depolarization in response to anti-Fas. Thus, the authors concluded that cell membrane depolarization per se is a crucial early step in anti-Fas-induced apoptosis [71].

Interestingly, the PCM depolarization was not a short-lasting phenomenon, as known from electrically excitable cells, but rather was sustained. We also saw in the T98G cell line over time (up to 6 h) a sustained PCM depolarization. This sustained PCM depolarization is an indication that upon apoptotic stimulation, the cells lose their ability to repolarize.

At this point it is important to mention the role of Bcl-2, the classic anti-apoptotic protein of the Bcl-2 family [72]. Usually, they are localized at the outer mitochondrial membrane, but recent studies discovered intracellular truncated forms in the neighborhood of the plasma cell membrane [73]. The most known function of Bcl-2 is exerted by inhibiting the oligomerization of Bcl-2-associated X protein (BAX) and Bcl-2-associated agonist of cell death protein (BAD) hereby preventing their pro-apoptotic effect.

But already decades ago the importance of Bcl-2 in modulating the plasma cell membrane has been stressed. We mentioned above the works of Gilbert and coworkers who observed that overexpression of the anti-apoptotic Bcl-2 gene is associated with membrane hyperpolarization rendering cells more resistant to radiation-induced apoptosis [61]. Further studies revealed that Bcl-2 itself has pore-forming domains similar to that of bacteria toxins and that the activation of K + channels by the myeloid leukemia cell differentiation protein (Mcl-1), a member of the Bcl-2 family, results in plasma cell membrane hyperpolarization [59, 74]. Finally, Lauf and coworkers could demonstrate a direct co-localization of Bcl-2 specifically with the NKA in the cell membrane providing the missing link to the hypothesized interaction between Bcl-2 and NKA [63].

The numerous functions of Ouabain on intracellular pathways are well described; one of them is the down-regulation of Bcl-2/Mcl-1 by accelerating its proteasomal degradation via reactive oxygen species (ROS) generation [75].

So, it seems, that Ouabain can not only depolarize the plasma cell membrane directly by inhibiting the NKA but additionally by down-regulating Bcl-2. We saw only in the TMZ-resistant T98G cell line a Bcl-2 down-regulation after treatment with Ouabain for 24 h at very low concentrations (0.01 nM) which unfortunately did not correlate with the concentrations, at which we observed PCM depolarization and cell migration inhibition. Consequently, in our study we could not confirm that Bcl-2 down-regulation contributes to PCM depolarization.

But with caution, we may interpret the down-regulation of Bcl-2 as a kind of sensitizing effect to facilitate e.g., apoptosis. Only recently, a Bcl-2 effect on cell migration was discovered [76,77,78]. In Fig. 1b we see a slight inhibitory effect of Ouabain on cell migration at very low (≤ 0.01 nM) concentrations which correlates exactly with those of Bcl-2 down-regulation (Fig. 5). As we outlined above, inhibition of cell migration is a prerequisite to apoptosis. Additional studies in future are needed and may focus not only on Bcl-2 but also on Mcl-1 expression [61, 63]. Interestingly, Wang and coworkers demonstrated that Mcl-1 causes a hyperpolarization of the PCMP through activation of K + channel activity [59] hereby preventing apoptosis.

At this point it should be stressed that Ouabain is known to have significant effects at nanomolar concentrations [56], e.g., at 0.1 to 10 nM the NKA is stimulated in non-malignant (cardiac and neuronal) cells, interestingly, via the high glycoside affinity α3 isoform [79].

As outlined above the PI3-K/Akt pathway is one important modulator of cell migration. We revealed in T98G cells an increase in p-Akt after 24 h treatment with 0.1 µM Ouabain. In contrast, LN229 cells did not show any change in p-Akt. It contradicts the anti-migratory effect of Ouabain which we revealed at 0.1 µM in T98G cells. In fact, we expected a p-Akt down-regulation, at least after prolonged 24 h treatment similar to Chen and coworkers, who observed a p-Akt down-regulation at 2.5 µM Ouabain in U-87 GBM cells [46].

The significant decreased level of pan-Akt after 24 h Ouabain treatment at 1 µM hints to a different mechanism by which Ouabain exerts its antitumor effects. You and coworkers were concerned about the short-lasting effects of phosphorylation inhibitors and developed a pan-AKT degrader by conjugating the Akt-phosphorylation inhibitor GDC-0068 to Lenalidomide. He showed that this compound (INY-03–041) induced significant degradation of all Akt isoforms at 24 h and, interestingly, improved the anti-proliferative effects compared to GDC-0068 alone [80].

Ouabain is known to contribute to degradation of several compounds in the signalosome by internalization and disturbed intracellular trafficking [81, 82]. With specific respect to the epidermal growth factor receptor (EGFR) Hafner and coworkers described in lung cancer A549 cells a specific phenomenon called endosomal arrest. After treatment with Ouabain, Digoxin, or Acovenoside they revealed persistent granules with internalized EGF-receptor without further degradation [83].

This endosomal arrest may be considered as a crucial checkpoint in cell biology [84] by diverting growth factors either to the recycling or the degradation pathway. In case of prolonged endosomal arrest, however, they are simply “stuck there”, losing any biological function.

We assume that pan-Akt like other compounds of the signalosome is endocytosed upon prolonged Ouabain stimulation and undergoes an endosomal arrest together with NKA α-subunits and EGFR. Indeed, it was shown that endosomal Akt is associated with the intracellular trafficking of growth factor receptor complexes and thus modifying their activity in a time and location dependent manner [85].

The peak in Akt activation (p-Akt Ser473) at prolonged lower doses of Ouabain might serve as a stimulus for inducing its degradation. Kometiani and coworkers stressed the time factor in intracellular activation processes i.e., while short term activation of ERK1/2 induced cell proliferation, sustained ERK1/2 activation resulted in increased expression of the cyclin-dependent kinase inhibitor 1 (p21Cip1) resulting in growth arrest [86]. Hence, this could be the main mechanism by which e.g., pan-Akt is down-regulated resulting in inhibition of migration and induction of apoptosis. Further studies certainly are here needed.

The reciprocal response of LN229 and T98G cells to Ouabain resp. Temozolomide is striking and may have significant clinical consequences. The underlying mechanisms are not yet known. There is evidence that Ouabain induces different endocytotic trafficking and signaling pathways according to the EGFR mutation status, the NKA isoforms [56, 87] and other not yet fully analyzed factors. Many authors described the interaction between NKA and EGFR e.g., Liu and Shapiro analyzed in the renal cell line LLC-PK1 the role of the signalosome in the process of endocytosis and demonstrated that Ouabain-stimulated endocytosis of the NKA is dependent on Caveolin-1 and Clathrin as well as the activation of c-Src, transactivation of EGFR and activation of phosphoinositide 3-kinase (PI3K). They showed that c-Src, EGFR, and the extracellular signal-regulated kinases 1 and 2 (ERK1/2) all were endocytosed along with the plasmalemmal NKA [81].

We did not analyze the NKA isoforms in our GBM cell lines but as shown by Chen and coworkers the T98G cell line is characterized by a high NKA α3/ α1 isoform ratio. He stressed that the high expression of the α3 isoform in the T98G cell line was correlating with a higher sensitivity to the apoptosis inducing effect of Ouabain [46]. Xiao and coworkers proved that the knockdown of the α3 isoform with siRNA impaired the anti-proliferative effect of Ouabain, indicating that Ouabain preferentially binds to the NKA α3 isoform [88]. Future studies are warranted to analyze the exact role of EGFR- and NKA isoform expression at the cell surface in directing ouabain-induced signaling either towards enhanced or reduced cell proliferation and migration.

Last, but not least, we could demonstrate for the first time an anti-angiogenic effect of Ouabain at low concentrations (0.01 µM) which correlated significantly with the inhibitory effect on cell migration (Fig. 7). Angiogenesis is considered as prerequisite for migration and invasion of tumor cells [89,90,91] and as such it constitutes an important target for cancer therapy, especially the hypervascularized gliomas. Bevacizumab a humanized monoclonal antibody against VEGF was approved in the treatment of recurrent GBM but, at least as monotherapy, it prolonged only the progression-free survival, but not the overall survival [92, 93]. The effect of Ouabain on angiogenesis resp. endothelial cells is rarely investigated [94, 95]. Trenti and coworkers revealed that Digitoxin in therapeutic range (1–25 nM) inhibited effectively angiogenesis via focal adhesion kinase (FAK) inhibition (51). At the same time Digitoxin as well as Ouabain protected HUVEC cells from apoptosis induced by growth factor deprivation (51). Dual actions of all CTS—dependent on cell types and dose regimen—remain a scientific and therapeutic challenge we have to accept and address in future studies.

AI writing tools could hand scientists the ‘gift of time’

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ChatGPT might not yet give us sparkling prose. But it can free scientists up to focus on more-stimulating writing tasks, says John Tregoning.

User holding Smartphone with ChatGPT service, in background blurred ChatGPT prompt on a laptop with code programming.

Many of us have already been trying ChatGPT. If you’ve checked science social media recently, it’s likely that you’ve already seen many of its writings. In common with many other researchers, I worry about artificial intelligence (AI) replacing me. I’m a vaccine researcher and spend much of my time writing grant applications, papers and articles about science careers, so I set the chatbot the task of writing an opinion piece about the use of AI in grant writing.

In less than a minute, ChatGPT had produced the following:

In my opinion, ChatGPT has the potential to revolutionize the process of writing scientific grants. Traditionally, writing a scientific grant has been a time-consuming and often frustrating process. Researchers spend countless hours crafting proposals, only to have them rejected by funding agencies. This can be demoralizing, and it can also be a barrier to progress in scientific research. ChatGPT has the potential to change all of this. By using natural language processing and machine learning, ChatGPT can help researchers write more compelling and effective grant proposals. It can also help reviewers assess grant proposals more efficiently, allowing for a more efficient and fair grant review process. Of course, ChatGPT is not a magic solution to all of the challenges facing scientific research. But it has the potential to make a real difference, and it is worth exploring as a tool for improving the grant writing and review process.Are ChatGPT and AlphaCode going to replace programmers?

Which, as my editor for this piece says, is pretty good for an AI program, but not good enough to be deemed worth publishing as a standalone piece of writing. It is, however, a massive step forwards. The simplicity and utility of platforms such as ChatGPT mean that we’ll see them quickly drifting into everyday use; Microsoft is already working closely with OpenAI, the company that developed ChatGPT – and you might already be using an AI platform to help you with some writing tasks. At present, ChatGPT is freely available, but things are moving extremely fast, so it is hard to know what will happen next.

Something to build on

The example above wasn’t the first time I’d used AI for science writing. My first real use of AI chatbots (beyond asking one to write lyrics to a song called ‘Eggy Eggy Woof Woof’ for my daughter) was when I got fed up with writing one part of a grant application. I was asked to explain the world-changing ‘impact’ that my science would have, if I was lucky enough to receive funding.

So I asked ChatGPT: “What impact could vaccine research have?” and got 250 words of generic fluff. It suggested reducing the burden of disease, saving lives, improving global health and supporting economic development. None of what it said was in any way original or enormously surprising, but it was an excellent starting point, which I could then flesh out with specifics.

So far, I’ve found AI to be enormously helpful at generating a lot of the low-level filler documents that otherwise take up time. For example, it can write easy, generic, on-the-one-hand-this-but-on-the-other-that statements about Internet-usage policy or data management. However, it’s still early days, and much more thought needs to go into exploring the implications of AI regarding plagiarism and attributing credit.‘Arms race with automation’: professors fret about AI-generated coursework

Various publishers (including Springer Nature, which publishes Nature) have scrambled to make clear their policies on using generative-text models. Generally, these models are seen as methods, rather than as co-authors, because they can’t take responsibility for the work. But questions remain. For example, the vast corpus of language that’s used to train many AI models will include some copyrighted material: how do we know that these models aren’t simply quoting something from a protected source?

One situation in which I have found ChatGPT extremely useful is writing multiple-choice questions. It’s quite easy to write a question and the right answer, but coming up with three plausible wrong answers is tricky. I found that if I prompted ChatGPT with the following: “Write a multi-choice question about <topic of interest> with four answers, and not using ‘all of the above’ as an answer,” it came up with good wrong answers. This was incredibly helpful. As someone suggested on Twitter, if students are going to use ChatGPT to help them write answers, we might as well use it to set the questions!

Generic waffle

Another time, I entered the prompt: “Write a diversity statement for a grant application.” The output starts:

Diversity is a core value at our organization and we are committed to promoting and maintaining an inclusive and equitable environment for all individuals.

It continues for 169 words that are generic to the point of being meaningless. Anyone can write such a response, and it requires no evidence or backing. It would be better if the grant-application form asked questions that an AI program can’t answer, such as: “Give examples of how your organization is promoting diversity, and evidence of the impact that these activities have had.” This could be applied to a whole range of questions that we are forced to answer.ChatGPT: five priorities for research

This made me reflect: if there is a section in a grant application that can be written by an AI, does that section really serve any purpose? If a computer can churn out something deeply generic that still answers the question (more or less), why are we asking people to address the question at all? I think the answer is clear: these sections never really did serve a purpose and certainly don’t now. For science and the process of grant writing to be improved, two things have to happen: first, the pointless sections (those that might as well have been written by a computer, and could just as easily be answered by one) need to be removed; and second, the sections that remain need to be changed in scope, to be shorter and action-centred.

But for now, while we are forced to fill in unnecessary boxes on forms, AI offers a way to free up headspace, which should be a good thing. In a Nature article last month about a decline in ‘disruptive’ science1, one of the suggestions was that academics needed “the gift of time”. AI could well give us this gift.

Freedom to be disruptive

The question is, then, how do we use the time given? One comparator is the automatic washing machine: as it became universal in the 1970s, it freed up time, which was then taken up with other household tasks. The sociologist Joann Vanek argued in 1974 that despite new household devices, the time devoted to housework had not changed over the past half-century2. Her argument has been debated, but the key question is what impact do time-saving devices have? Are we going to fill the time saved by AI with other low-value tasks, or will it free us to be more disruptive in our thinking and doing?Tools such as ChatGPT threaten transparent science; here are our ground rules for their use

I have some unrealistically high hopes of what AI can deliver. I want low-engagement tasks to take up less of my working day, allowing me to do more of what I need to do to thrive (thinking, writing, discussing science with colleagues). And then, because I won’t have a Sisyphean to-do list, I’ll be able to go home earlier — because I’ll have got more of the thinking, writing and discussing done during working hours, rather than having to fit them around the edges.

We are unlikely to arrive at these sunlit uplands without some disruption. Just as domestic appliances significantly shrank the need for domestic staff, AI is going to change the labour market. For some tasks, AI will replace people. The aim of the game is to not do a job that can be replaced by an AI program. Hopefully, I have persuaded you that although AI can write, it isn’t going to replace me or others in my profession immediately. I’m not the only one to see things this way: the songwriter Nick Cave put it much more eloquently here. One piece of good news for me is that AI isn’t very good at telling jokes. I will leave you with its best effort:

Why was the math book sad? Because it had too many problems.

Source: Nature

Cancer-Causing Viruses Hijack Human Protein to Evade Immune Response

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Viruses have evolved with humans for millions of years, so it’s no surprise they’ve evolved tricks to evade our natural, or innate, immune responses. Unfortunately, it’s often unclear what these tricks are. But now, thanks to researchers at the University of North Carolina (UNC) School of Medicine, one of these tricks has been revealed. It is particular to gammaherpesviruses, which include Kaposi sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV).

These viruses, which are DNA viruses, have been linked to several cancers and establish lifelong latency in the human population. According to the UNC researchers, these viruses use a human protein called barrier-to-autointegration factor 1, or BAF, to evade our innate immune response, allowing the viruses to spread and cause disease.

The researchers suggest that BAF and related proteins could prove to be valuable therapeutic targets. Indeed, if these targets can be engaged, it may be possible to prevent virus-instigated cancers such as Kaposi sarcoma, non-Hodgkin lymphoma, Hodgkin lymphoma, multicentric Castleman disease, nasopharyngeal carcinoma, and gastric cancer.

Details about the new research appeared in Nature Communications, in an article titled, “Barrier-to-autointegration factor 1 promotes gammaherpesvirus reactivation from latency.”

“We report that barrier-to-autointegration factor 1 (BAF)-mediated suppression of the cGAS-STING signaling pathway is necessary for reactivation of KSHV and EBV,” the article’s authors wrote. “We demonstrate a role for BAF in destabilizing cGAS expression and show that inhibiting BAF expression in latently infected, reactivating, or uninfected cells leads to increased type I interferon-mediated antiviral responses and decreased viral replication. Furthermore, BAF overexpression resulted in decreased cGAS expression at the protein level.”

The research was led by Blossom Damania, PhD, the Boshamer distinguished professor of microbiology and immunology and member of the Lineberger Comprehensive Cancer Center. She stated, “Viruses are in a constant battle with the cellular immune system, which includes the protein cyclic GMP-AMP synthase, or cGAS, which binds to viral DNA and sounds the alarm to trigger immune responses and fight the viral invaders. We’ve discovered that KSHV and EBV use a different host cell protein, BAF, to prevent cGAS from sounding the alarm.”

In the case of KSHV and EBV, the expression of BAF is increased upon infection, suggesting that these viruses take advantage of this host protein to blunt the immune response to infection. In a series of experiments, Damania’s laboratory found that BAF contributes to the degradation of the cGAS DNA sensor. With less cGAS protein available in the infected cell to detect DNA, the cells mount weaker immune responses, which allows these two viruses to replicate and spread more efficiently.

“BAF enables EBV and KSHV to reactivate from latency, replicate, and make more of themselves,” said first author Grant Broussard, a graduate student in the genetics and molecular biology curriculum at UNC Lineberger. “Our study highlights the prominent role that DNA detection pathways like the cGAS pathway play in controlling viral infection.”

He stressed that disrupting BAF activity with targeted therapies could reduce its immunosuppressive effects, thus restricting replication of these viruses to prevent the spread of disease.

Damania, who is a Leukemia and Lymphoma Society scholar and a Burroughs Wellcome Fund investigator in infectious diseases, added, “Preventing lytic replication will prevent transmission of these viruses and also reduce the global cancer burden associated with these two viruses.”

How Intermittent Fasting Extends Life Spans – Time-Restricted Eating Reshapes Gene Expression Throughout the Body

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Time-restricted eating reshapes gene expression throughout the body. In this illustration, the Ferris wheel displays the interconnected organ systems working smoothly during time-restricted eating, which is represented by the clock in the middle.

Salk researchers find that timing calorie intake synchronizes circadian rhythms across multiple systems in mice.

Numerous studies have shown health benefits of time-restricted eating including increase in life span in laboratory studies. This has made practices like intermittent fasting a hot topic in the wellness industry. However, exactly how it affects the body on the molecular level, and how those changes interact across multiple organ systems, has not been well understood. Now, Salk scientists show in mice how time-restricted eating influences gene expression across more than 22 regions of the body and brain. Gene expression is the process through which genes are activated and respond to their environment by creating proteins.

The findings, published in Cell Metabolism on January 3, 2023, have implications for a wide range of health conditions where time-restricted eating has shown potential benefits, including diabetes, heart disease, hypertension, and cancer.

Satchidanananda Panda

Satchidanananda Panda. Credit: Salk Institute

“We found that there is a system-wide, molecular impact of time-restricted eating in mice,” says Professor Satchidananda Panda, senior author and holder of the Rita and Richard Atkinson Chair at Salk. “Our results open the door for looking more closely at how this nutritional intervention activates genes involved in specific diseases, such as cancer.”

For the study, two groups of mice were fed the same high-calorie diet. One group was given free access to the food. The other group was restricted to eating within a feeding window of nine hours each day. After seven weeks, tissue samples were collected from 22 organ groups and the brain at different times of the day or night and analyzed for genetic changes. Samples included tissues from the liver, stomach, lungs, heart, adrenal gland, hypothalamus, different parts of the kidney and intestine, and different areas of the brain.

The authors found that 70 percent of mouse genes respond to time-restricted eating.

“By changing the timing of food, we were able to change the gene expression not just in the gut or in the liver, but also in thousands of genes in the brain,” says Panda.

Nearly 40 percent of genes in the adrenal gland, hypothalamus, and pancreas were affected by time-restricted eating. These organs are important for hormonal regulation. Hormones coordinate functions in different parts of the body and brain, and hormonal imbalance is implicated in many diseases from diabetes to stress disorders. The results offer guidance to how time-restricted eating may help manage these diseases.

Interestingly, not all sections of the digestive tract were affected equally. While genes involved in the upper two portions of the small intestine—the duodenum and jejunum—were activated by time-restricted eating, the ileum, at the lower end of the small intestine, was not. This finding could open a new line of research to study how jobs with shiftwork, which disrupts our 24-hour biological clock (called the circadian rhythm) impact digestive diseases and cancers. Previous research by Panda’s team showed that time-restricted eating improved the health of firefighters, who are typically shift workers.

The researchers also found that time-restricted eating aligned the circadian rhythms of multiple organs of the body.

“Circadian rhythms are everywhere in every cell,” says Panda. “We found that time-restricted eating synchronized the circadian rhythms to have two major waves: one during fasting, and another just after eating. We suspect this allows the body to coordinate different processes.”

Next, Panda’s team will take a closer look at the effects of time-restricted eating on specific conditions or systems implicated in the study, such as atherosclerosis, which is a hardening of the arteries that is often a precursor to heart disease and stroke, as well as chronic kidney disease.

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Time-restricted eating reshapes gene expression throughout the body. In this illustration, the Ferris wheel displays the interconnected organ systems working smoothly during time-restricted eating, which is represented by the clock in the middle. Credit: Salk Institute

Salk researchers find that timing calorie intake synchronizes circadian rhythms across multiple systems in mice.

Numerous studies have shown health benefits of time-restricted eating including increase in life span in laboratory studies. This has made practices like intermittent fasting a hot topic in the wellness industry. However, exactly how it affects the body on the molecular level, and how those changes interact across multiple organ systems, has not been well understood. Now, Salk scientists show in mice how time-restricted eating influences gene expression across more than 22 regions of the body and brain. Gene expression is the process through which genes are activated and respond to their environment by creating proteins.

The findings, published in Cell Metabolism on January 3, 2023, have implications for a wide range of health conditions where time-restricted eating has shown potential benefits, including diabetes, heart disease, hypertension, and cancer.

Satchidanananda Panda

Satchidanananda Panda. Credit: Salk Institute

“We found that there is a system-wide, molecular impact of time-restricted eating in mice,” says Professor Satchidananda Panda, senior author and holder of the Rita and Richard Atkinson Chair at Salk. “Our results open the door for looking more closely at how this nutritional intervention activates genes involved in specific diseases, such as cancer.”

For the study, two groups of mice were fed the same high-calorie diet. One group was given free access to the food. The other group was restricted to eating within a feeding window of nine hours each day. After seven weeks, tissue samples were collected from 22 organ groups and the brain at different times of the day or night and analyzed for genetic changes. Samples included tissues from the liver, stomach, lungs, heart, adrenal gland, hypothalamus, different parts of the kidney and intestine, and different areas of the brain.

The authors found that 70 percent of mouse genes respond to time-restricted eating.

“By changing the timing of food, we were able to change the gene expression not just in the gut or in the liver, but also in thousands of genes in the brain,” says Panda.

Nearly 40 percent of genes in the adrenal gland, hypothalamus, and pancreas were affected by time-restricted eating. These organs are important for hormonal regulation. Hormones coordinate functions in different parts of the body and brain, and hormonal imbalance is implicated in many diseases from diabetes to stress disorders. The results offer guidance to how time-restricted eating may help manage these diseases.

Interestingly, not all sections of the digestive tract were affected equally. While genes involved in the upper two portions of the small intestine—the duodenum and jejunum—were activated by time-restricted eating, the ileum, at the lower end of the small intestine, was not. This finding could open a new line of research to study how jobs with shiftwork, which disrupts our 24-hour biological clock (called the circadian rhythm) impact digestive diseases and cancers. Previous research by Panda’s team showed that time-restricted eating improved the health of firefighters, who are typically shift workers.

The researchers also found that time-restricted eating aligned the circadian rhythms of multiple organs of the body.

“Circadian rhythms are everywhere in every cell,” says Panda. “We found that time-restricted eating synchronized the circadian rhythms to have two major waves: one during fasting, and another just after eating. We suspect this allows the body to coordinate different processes.”

Next, Panda’s team will take a closer look at the effects of time-restricted eating on specific conditions or systems implicated in the study, such as atherosclerosis, which is a hardening of the arteries that is often a precursor to heart disease and stroke, as well as chronic kidney disease.