Publisher Health

There’s been a recent push in the U.S. to make naloxone — a fast-acting opioid antidote — available without a prescription. This medication has saved lives, but it’s less effective against powerful synthetic opioids, such as fentanyl. In an interesting twist, researchers are now looking to cannabidiol (CBD), a component of marijuana, as a possible alternative to the popular antidote. Today, a team reports compounds based on CBD that reduce fentanyl binding and boost the effects of naloxone.
The researchers will present their results at the spring meeting of the American Chemical Society (ACS). ACS Spring 2023 is a hybrid meeting being held virtually and in-person March 26-30, and features more than 10,000 presentations on a wide range of science topics.
“Fentanyl-class compounds account for more than 80% of opioid overdose deaths, and these compounds aren’t going anywhere — it’s just too much of an economic temptation for dealers,” says Alex Straiker, Ph.D., the project’s co-principal investigator. “Given that naloxone is the only drug available to reverse overdoses, I think it makes sense to look at alternatives.”
A new option could take one of two forms, according to Michael VanNieuwenhze, Ph.D., the other co-principal investigator for the project.
“Ideally, we would like to discover a more potent replacement for naloxone,” VanNieuwenhze says. “However, finding something that works synergistically with it, reducing the amount needed to treat an overdose, would also be a success.”
Jessica Gudorf, a graduate student in VanNieuwenhze’s group, is presenting the work at the meeting. All of the researchers are at Indiana University Bloomington.

Opioids are a class of compounds that are prescribed to treat pain and are sometimes sold illegally. If taken in excess, the drugs can interfere with breathing, making them potentially lethal. The U.S. Centers for Disease Control and Prevention estimates that more than half a million people died from overdoses involving opioids between 1999 and 2020. That toll continues to climb.
Compared to other compounds in this class, such as heroin or morphine, fentanyl and its other synthetic relatives bind more tightly to opioid receptors in the brain. Naloxone reverses an overdose by competing with the drug molecules for the same binding sites on the receptors. But because fentanyl binds so readily, it has a leg up on naloxone, and growing evidence suggests that reversing these kinds of overdoses may require multiple doses of the antidote.
At this point, researchers have exhaustively studied the strategy naloxone takes, but they have yet to find any way to improve on its performance, Gudorf says. “Our work opens the door to making new blockers that work through a different mechanism,” she explains.
Earlier research suggesting that CBD can interfere with opioid binding inspired the current effort. In research published in 2006, a group based in Germany concluded that CBD hampered opioid binding indirectly, by altering the shape of the receptor. When used with naloxone, they found CBD accelerated the medication’s effect, forcing the receptors to release opioids.
To augment these effects, Gudorf altered CBD’s structure to generate derivatives. Taryn Bosquez-Berger, a graduate student in Straiker’s group, tested these new compounds in cells with a substance called DAMGO, an opioid used only in lab studies. To measure their success, she monitored a molecular signal that diminishes when this type of drug binds. Armed with feedback from these experiments, Gudorf refined the structures she generated.
In the end, they narrowed the field to 15, which they tested at varying concentrations against fentanyl, with and without naloxone. Several derivatives could reduce fentanyl binding even at what Bosquez-Berger described as “incredibly low” concentrations, while also outperforming naloxone’s opioid-blocking performance. Two of these also showed a synergistic effect when combined with the antidote.
The team has since begun testing the most successful derivatives in mice. In these experiments, they are investigating whether these compounds alter behaviors associated with taking fentanyl.
“We hope our approach leads to the birth of new therapeutics, which, in the hands of emergency personnel, could save even more lives,” Bosquez-Berger says.
The researchers acknowledge support and funding from the Indiana University Grand Challenges Program.

Have a cough, sore throat and congestion? Any number of respiratory viruses could be responsible. Conventional tests can identify certain likely culprits by relying on chemical reactions, but some researchers want to swap chemistry for electrical changes sensed by nanomaterials. Today, scientists report using a single-atom-thick nanomaterial to build a device that can simultaneously detect the presence of the viruses that cause COVID-19 and the flu — at much lower levels and much more quickly than conventional tests for either.
The researchers will present their results at the spring meeting of the American Chemical Society (ACS). ACS Spring 2023 is a hybrid meeting being held virtually and in-person March 26-30, and features more than 10,000 presentations on a wide range of science topics.
The symptoms of both flu and COVID-19 overlap considerably, making it difficult to distinguish between them, notes Deji Akinwande, Ph.D., who is presenting the work at the meeting.
“When both of these viruses are circulating together as they did earlier this winter, it would be immensely useful to have a sensor that can simultaneously detect whether you have COVID, flu, none of the above or both,” he says.
Akinwande, who is at The University of Texas at Austin, says that the device he and colleagues are developing could be modified to test for other infections as well.
The group, including Dmitry Kireev, Ph.D., a postdoc in Akinwande’s lab, constructed the COVID-19 and flu sensor using graphene, a single layer of carbon atoms arranged in a hexagonal lattice pattern. Its extreme thinness renders graphene highly sensitive to any electrical changes in its environment. Akinwande and other researchers see enormous potential in using it and other, similar nanomaterials to create sensors for many different applications.

“These ultra-thin nanomaterials generally hold the record for best sensitivity, even down to the detection of single atoms, and they can improve the ability to detect very small quantities of basically anything that needs to be sensed, whether it’s bacteria or viruses, in gas or in blood,” Akinwande says.
Previously, his group reported designing a graphene-based temporary tattoo that could monitor blood pressure. The tattoo consists of pairs of sensors placed along the arteries of the arm. One half of each pair sends out an electrical current that its partner detects. This signal is used to determine blood flow.
To build the infection sensor, the researchers had to make graphene respond to the presence of viral protein. To do so, they looked to the immune system, which produces antibodies that are fine-tuned to recognize and latch onto particular pathogens. The researchers linked antibodies against SARS-CoV-2, the virus that causes COVID-19, and against the flu virus to graphene. When a sample from an infected person is placed on the sensor, these antibodies bind to their target proteins, prompting a change in the electrical current.
The researchers did not have the safety facilities needed to use whole, active flu or SARS-CoV-2 viruses to test the roughly square-inch sensor. To substitute, they used proteins from these viruses delivered in fluid intended to resemble saliva. Their results indicated that not only could the sensor detect the presence of the proteins, it could do so when they were present at extremely low quantities. This sensitivity suggested the sensor could be used for detecting the much more sparse viral particles found in breath, Akinwande says.
The sensor also worked quickly, returning results within about 10 seconds of dropping in a sample, he says. By comparison, conventional COVID-19 tests can take minutes or hours, depending on the type, and a dual COVID and flu test recently authorized by the U.S. Food and Drug Administration takes about half an hour to produce results.
Akinwande and his group are working to improve its performance further, including by expanding the slate of viruses it can detect. With funding from the National Science Foundation, they are developing a sensor designed to test for SARS-CoV-2 variants, such as omicron and delta. While they are currently focusing on a two-variant design, the test could be adapted to simultaneously identify even more, they say.
The researchers acknowledge support and funding from the National Science Foundation.

Steroid hormones, to which belong sex hormones like estrogen or testosterone, are important signaling molecules and are responsible among other things for controlling female and male phenotypic sex differentiation. They act by binding to receptor molecules that switch on and off the activity of hormone-dependent genes. Researchers at the University of Freiburg and Kiel University Hospital have discovered that components of the cytoskeleton are critically involved in this process. The findings are relevant for the diagnosis of medical conditions and the study of diseases and cancers in which steroid hormones play important roles. The study was published in the journal Nature.
The new research findings show that filamentous actin, a component of the cytoskeleton, interacts with the androgen receptor directly in the cell nucleus and strengthens its effect. The androgen receptor mediates the signals of sex hormones for male sex development but also promotes the progression of prostate cancer.
A genetic modification as the key indicator
Scientists with different research foci from Freiburg, Kiel, and Lübeck collaborated on the study across disciplines. The project was led jointly by Prof. Dr. Robert Grosse and PD Dr. Nadine Hornig: Grosse conducts his research at the Cluster of Excellence CIBSS — Centre for Integrative Biological Signalling Studies and the University of Freiburg’s Faculty of Medicine, Hornig at University of Kiel´s Faculty of Medicine and the University Hospital Schleswig-Holstein, campus Kiel.
The researchers became aware of the previously unknown connection between actin and steroid hormones while studying the cells of patients with a so-called androgen insensitivity syndrome (AIS). People who live with AIS have a set of male XY chromosomes but have less pronounced male sexual characteristics, extending even to a completely female appearance. This is often due to a change in the androgen receptor, which means that male sex hormones can no longer take effect. However, the androgen receptor is frequently unchanged in patients with AIS.
“We want to find out what genetic modifications cause AIS in these patients,” explains Hornig. “Thus, we wanted to identify further molecules that play a role in the development of sexual characteristics.” For this purpose, the researchers used a screening method to examine the cells of patients with AIS. In the process, they discovered mutations in the DAAM2 gene in two patients: The molecule belongs to the group of formins and controls the dynamic polymerization and elongation of actin filaments. As a part of the cytoskeleton, actin is important for the stability and locomotion of cells but also serves regulatory functions.
High-resolution microscopy reveals the processes in the cell nucleus
The researchers used high-resolution 3D SIM microscopy to examine whether DAAM2 is indeed important for the effect of sex hormones. This is an elaborate technique that can be used to observe molecular movements within cells. The images show that DAAM2 and actin colocalize with the androgen receptor directly in the cell nucleus. Further experiments demonstrated that this colocalization is important for the control of gene activity.
“This is a completely unknown mode of action, which we succeeded in describing here for a very important receptor,” says Grosse, highlighting the significance of the new findings. The research team assumes that the mechanism could be widespread and also influences the effect of other steroid hormones. “This could play a role in many physiological processes and diseases. It will be exciting to see whether it will enable new therapeutic approaches,” explains Grosse.
Diagnosis possible for more patients with AIS
The discovery also provides a basis for further research on the development of sexual characteristics and enables a clear diagnosis for more patients with AIS: “Previously, patients with androgen insensitivity but without a modification in the androgen receptor did not receive a clear diagnosis despite having clear symptoms,” says Hornig. “Now we can make a clear diagnosis for those in whom DAAM2 is altered.”

New UCLA research in mice suggests that “dormant” cone photoreceptors in the degenerating retina are not dormant at all, but continue to function, producing responses to light and driving retinal activity for vision.
The cells in the retina that produce the visual experience are rods and cones. Rods are active in dim light and cones in daylight. Mutations in rods that cause them to die trigger most inherited retinal degeneration. Cones can remain alive after nearly all the rods die, but they retract key parts of the cells and appear “dormant.”
But while past literature suggested that dormant cells were not functional, and earlier attempts to record from them revealed no light-driven activity, the new study indicates for the first time that the cells are still viable. Furthermore, downstream signals recorded from the retina show that visual processing is not as compromised as may be expected. The authors say their findings demonstrate that therapeutic interventions to protect these cells, or enhance their sensitivity, have the capability to preserve nearly normal daytime vision.
“While the sensitivity of the cones was about 100-1000 fold less than normal, we were surprised to find that that the drop-off in sensitivity for the ganglion cells that project to the brain was much less,” said senior author Alapakkam Sampath, the Grace and Walter Lantz Endowed Chair in Ophthalmology at the UCLA Jules Stein Eye Institute and professor at the David Geffen School of Medicine at UCLA. “It seems that adaptational mechanisms in the inner retina might be trying to minimize the sensitivity difference to preserve robust signaling in the ganglion cells — this is consistent with what we know about the brain. Homeostatic mechanisms that respond to injury and disease typically cover up the deficiency. That is why it is hard to detect neurological problems until the deficiency becomes very severe.”
The study is published in the peer-reviewed journal of Current Biology.
The investigators examined membrane properties of cones in mice following the degeneration of rods. The patch clamp recording method is a laboratory technique for studying currents in living cells while controlling the cell’s membrane potential, or membrane voltage. These single cell recordings can establish key features of the cell’s activity, including the presence of specific membrane currents, whether the cell has light responses, and whether they might connect to downstream neurons in the retina. In addition, the investigators used multi-electrode array recordings that establish the activity of all retinal ganglion cells, and that can show the ganglion cell’s ability to respond to visual stimuli that vary in spatial location over time.
These recordings revealed that the remaining cones in a retina where the rods have mostly degenerated were still functional. Although the anatomic specializations that are responsible for generating the light response — or phototransduction — and the synaptic connection to downstream cells were missing, these functions remained with less sensitivity than normal. These cells still display many of the features of normal cones, including a similar resting membrane potential, a normal synaptic Ca2+ current, and light responses even though they no longer have the part of the cell that was traditionally thought needed for the light response. Furthermore, the ganglion cells retain their ability to respond to visual stimuli with similar spatial and temporal sensitivity.
“These important results may suggest a future path forward for patients with conditions thought to be causing irreversible retinal blindness, as photoreceptor or cone viability in tissue was previously thought to be irreparably damaged,” said Dr. Steven Schwartz, Ahmanson chair in ophthalmology at the David Geffen School of Medicine at UCLA, and professor and Retina Division chief at the UCLA Jules Stein Eye Institute.
The next step for researchers is to establish the extent to which the neuroprotection or enhancement of the dormant cones will allow the rescue of vision in various forms of blindness.
The researchers were supported by grants from the National Eye Institute (R01EY033035, R01EY027442, R01EY27193, R01EY001844, R01EY27193 and EY29817), a fellowship of the UCLA EyeSTAR program of the UCLA Department of Ophthalmology, a BrightFocus Foundation Postdoctoral Fellowship, an unrestricted grant from Research to Prevent Blindness USA to the UCLA Department of Ophthalmology and National Eye Institute Core Grant (P30) EY00311 to the Jules Stein Eye Institute.
The study’s other authors are Dr. Erika Ellis, Antonio Paniagua, Yuekan Jiao, David Williams, Gordon Fain, all of UCLA; and Miranda Scalabrino, Mishek Thapa, Jay Rathinavelu and Greg Field, all of Duke University. The Field laboratory has recently moved to the UCLA Jules Stein Eye Institute. The authors declare no competing interests.

For the first time, researchers have developed a form of the omega-3 fatty acid docosahexaenoic acid (DHA) that is capable of crossing into the eye’s retina to ward off visual declines related to Alzheimer’s disease, diabetes and other disorders.
The DHA found in fish oil capsules and other supplements is typically in a form called triacylglycerol (TAG) DHA. Although TAG-DHA has benefits in other parts of the body, it does not reach the eyes because it cannot travel from the bloodstream into the retina. For the study, researchers created a new lysophospholipid form of DHA, or LPC-DHA. In studies using mice, LPC-DHA successfully increased DHA in the retina and reduced eye problems associated with Alzheimer’s-like processes.
“Dietary LPC-DHA is enormously superior to TAG-DHA in enriching retinal DHA and could be potentially beneficial for various retinopathies in patients,” said Sugasini Dhavamani, a research assistant professor in the Department of Medicine at the University of Illinois at Chicago. “This approach provides a novel therapeutic approach for the prevention or mitigation of retinal dysfunction associated with Alzheimer’s disease and diabetes.”
Dhavamani will present the research at Discover BMB, the annual meeting of the American Society for Biochemistry and Molecular Biology, March 25-28 in Seattle.
In healthy eyes, DHA is concentrated in the retina, where it helps maintain photoreceptors, the cells that convert light into signals that are sent to the brain. DHA deficiency in the retina is associated with vision loss. People with Alzheimer’s disease, as well as those with diabetes, retinitis pigmentosa, age-related macular degeneration and peroxisomal disorders, frequently have abnormally low levels of retinal DHA, and visual impairments are common as a result.
While boosting DHA can help to prevent such declines, increasing retinal DHA content has been challenging with currently available supplements. For a dietary supplement to deliver DHA to the retina, the DHA must be able to first be absorbed from the intestine into the bloodstream and then cross from the bloodstream into the retina.
“Increasing the retinal DHA at clinically feasible doses has not been possible until now because of the specificity of the blood-retinal barrier that is incompatible with the specificity of the intestinal barrier,” said Dhavamani. “This study uses the novel approach of dietary LPC-DHA that overcomes both intestinal and blood-retinal barriers and improves retinal function.”
The researchers tested their LPC-DHA supplement in mice bred to exhibit processes similar to those found in early-onset Alzheimer’s disease. After six months, mice that were fed LPC-DHA daily showed a 96% improvement in retinal DHA content as well as preserved retinal structure and function. In contrast, TAG-DHA supplements had no effect on retinal DHA levels or function.
The results suggest that LPC-DHA supplements could help to prevent Alzheimer’s-related declines in visual function. Researchers say the approach should also be helpful for other disorders in which DHA deficiency and vision impairment are common.
The dosage of LPC-DHA used in the study is equivalent to about 250 to 500 milligrams of omega-3 fatty acids per day in humans. Since these studies were conducted in mice, further studies would be needed to confirm that LPC-DHA is safe and effective for use in humans.
This work was supported by an Alzheimer’s Association Research Grant (AARG).

Growing concerns over the potential health effects of exposure to phthalates, a component of many plastics and also known as a plasticizer, have led to a search for safer alternatives. In a new study conducted in cell cultures, researchers found that the chemical acetyl tributyl citrate (ATBC) might not be the best replacement because it appears to interfere with the growth and maintenance of neurons.
“In the past, industries have promptly shifted away from the usage of toxic chemicals only to produce an equally toxic chemical, so this is something we are actively trying to avoid repeating,” said Kyle Sease, a graduate student at Central Washington University in Ellensburg, Washington. “Our study suggests that ATBC, but not other non-phthalate alternatives, could interfere with cells that maintain brain health. We think this finding warrants further testing of ATBC at different doses, in different settings and in whole organism models.”
Sease will present the new research at Discover BMB, the annual meeting of the American Society for Biochemistry and Molecular Biology, March 25-28 in Seattle.
Phthalates are used in hundreds of products, often to enhance durability or allow materials to bend and stretch. Studies have shown that phthalate exposure can affect the reproductive system and early development in a range of animals, although the health impacts in humans are not clear. ATBC has emerged as a leading phthalate alternative as companies seek to shift away from phthalates and is currently used in a variety of materials and products, including food and food packaging.
For the study, researchers grew cultures of neuroblastoma cells, which, in terms of growth and division, behave similarly to the glial cells that support and protect neurons in the brain. They then used molecular methods to study how ATBC and other chemicals affect genes and processes involved in cellular division. They found that neuroblastoma cells exposed to ATBC increased their expression of two genes associated with cellular stress (known as Nrf2 and p53) and also increased their production of an enzyme associated with cellular senescence (B-galactosidase), which can cause cells to stop growing and dividing.
The findings suggest that ATBC could interfere with the ability for glial cells to regenerate, which can reduce their ability to protect neural cells and lead to neurodegeneration and accelerated aging. It is also possible that ATBC exposure during early development — when neurons are actively growing and dividing — could affect neurons directly and interfere with brain development, the researchers said. Since neurons do not typically regrow once damaged, any effects on the brain likely would be permanent.
Two other phthalate alternatives, bis (2-ethylhexyl)-1, 4-benzenedicarboxylate (GPO) and dioctyl adipate (DOA), did not show the same effects as ATBC. “We found that two other plasticizers did not appear to affect cell division in these cells, so further understanding the different effects of different plasticizers will allow us to understand better how to make safe ones,” Sease said.
Kyle Sease will present this research from 4:30-6:30 p.m. PDT on Monday, March 27, in Exhibit Hall 4AB of the Seattle Convention Center (Poster Board No. 141) (abstract).

Malignant melanoma is a relatively aggressive type of skin cancer. When detected early, it is usually treatable by surgical resection only, but metastases develop often spreading to distant areas. Currently, tumor thickness and the presence of ulceration are some of the known prognostic factors used as indicators of malignant melanoma. Therefore, the discovery of valuable markers to assess the malignant potential of melanoma more accurately may be necessary to develop appropriate treatments.
Cross talk between cancer cells and surrounding stromal cells is believed to orchestrate cancer progression through a variety of mechanisms. Cancer-associated fibroblasts (CAFs) — key factors in the tumor microenvironment — in particular have been implicated in cancer cell progression. It has also been reported that the exosomes, a type of small vesicles, produced by CAFs play an important role in cancer progression.
A research group led by Naho Fujii, M.D., and Professor Hisashi Motomura from Osaka Metropolitan University Graduate School of Medicine investigated the effect of CAF-derived exosomes on the growth of malignant melanoma cells. The group found that the transmembrane proteins CD9 and CD63 were mainly present on CAF-derived exosomes, and that among the exosomes, the CD9-positive ones inhibited the growth of malignant melanoma cells.
“As a plastic surgeon, usually I provide surgical treatment for skin cancer, but I have wanted to study other treatment methods for a long time,” explained Fujii, M.D. “This study suggests that CD9-positive exosomes inhibit the growth of malignant melanoma, so CD9-positive exosomes may be a useful marker to evaluate the malignant grade of melanoma. We expect further research will lead to the development of new treatments in that line.”

Losing weight with lifestyle changes in an intensive behavioral weight loss program was associated with a decrease in risk factors for cardiovascular disease and Type 2 diabetes for at least five years — even if some weight was regained, according to a systematic review of research, published today in Circulation: Cardiovascular Quality and Outcomes, a peer-reviewed American Heart Association journal.
People affected by obesity or who are overweight are at increased risk for high cholesterol and high blood pressure — factors that heighten risk of cardiovascular disease; as well as insulin resistance, a precursor to Type 2 diabetes. Globally, overweight and obesity contributed to 2.4 million deaths in 2020, according to the American Heart Association’s 2023 Statistical Update.
Behavioral weight loss programs can help people lose and maintain a healthy weight by encouraging lifestyle and behavior changes, such as eating healthy foods and increasing physical activity. Regaining some weight is common after behavioral weight loss programs. Some observational studies suggest this weight change pattern of weight loss followed by weight regain may increase cardiovascular risk. However, according to the authors of this analysis, data from randomized trials and long-term follow-up studies is lacking.
“Many doctors and patients recognize that weight loss is often followed by weight regain, and they fear that this renders an attempt to lose weight pointless,” said study co-senior author Susan A. Jebb, Ph.D., a professor of diet and population health at the University of Oxford in the United Kingdom. “This concept has become a barrier to offering support to people to lose weight. For people with overweight or obesity issues, losing weight is an effective way to reduce the risk of Type 2 diabetes and cardiovascular disease.”
In this review, researchers assessed international scientific studies available in 2018 to compare risk factors for cardiovascular disease and Type 2 diabetes among people who followed an intensive behavioral weight loss program to those who followed a less intensive or no weight loss program. The studies in the analysis included diet and/or exercise interventions, partial or total meal replacement, intermittent fasting, or financial incentives contingent on weight loss. The studies took place in a variety of settings and included varying modes of delivery (in person, app-based, telephone, etc.).
Researchers combined the results of 124 studies totaling more than 50,000 participants, with an average follow-up of 28 months. They used the combined results to estimate changes in risk factors for cardiovascular disease and Type 2 diabetes after weight loss. The average weight loss across the different studies ranged from 2-5 kilograms, or 5-10 pounds. Weight regain averaged 0.12 to 0.32 kg (0.26 pounds to 0.7 pounds) a year. Participants were an average age 51 years old, with a body mass index of 33, which is considered obese.

Compared to people in a less intensive program and those in no weight loss program, participants who lost weight through an intensive weight loss program had lower risk factors for cardiovascular disease and Type 2 diabetes. These lower risk factors lasted for at least five years after the weight loss program ended.
Based on pooled results of the studies reviewed, on average: Systolic blood pressure, the top number in a blood pressure reading, was 1.5 mm Hg (millimeters of mercury) lower at one year, and 0.4 mm Hg lower at five years after participation in an intensive weight loss program. In addition, the percentage of HbA1c, a protein in red blood cells used to test for diabetes, was reduced by 0.26 at both one and five years after participation in an intensive weight loss program. The ratio of total cholesterol to good cholesterol – known as high-density lipoprotein (HDL) cholesterol — was 1.5 points lower one year and five years after participation in an intensive weight loss program.These changes are important because they represent improvements at the population level, Jebb explained.
In a preliminary finding, the decreased risk of being diagnosed with cardiovascular disease or Type 2 diabetes also appeared to remain lower even after weight regain. However, few studies followed people for more than 5 years and “more information is needed to confirm whether this potential benefit persists,” Jebb said.
“Most trials look at whether new treatments are effective and focus on weight change in the short-term rather than the effect on later disease,” Jebb said. “Individual studies are often too small to detect differences between groups in the incidence of cardiovascular conditions because, fortunately, they affect only a small proportion of the whole group, and studies may not continue long enough to see the effects on ‘hard’ outcomes, such as a new diagnosis of Type 2 diabetes or a heart attack.

“Our findings should provide reassurance that weight loss programs are effective in controlling cardiovascular risk factors and very likely to reduce the incidence of cardiovascular disease,” she said.
Evidence suggests that cardiovascular health is improved by following the American Heart Association’s Life’s Essential 8 health metrics: eating healthy food, being physically active, not smoking, getting enough sleep, maintaining a healthy weight, and controlling cholesterol, blood sugar and blood pressure levels.
The analysis had several limitations: information included in the review was not updated after 2019 and the review focused on research papers published in English, so eligible studies written in other languages may have been missed.
An accompanying editorial notes that much remains to be understood about various weight loss interventions, their long-term impact and how this impact may be diminished by regaining weight. Behavioral weight loss programs constitute the backbone of weight management in clinical practice. However, they are often resource intensive, and emerging medication therapies are expensive, according to editorial authors Vishal N. Rao, M.D., M.P.H., and Neha J. Pagidipati, M.D., M.P.H., both from the division of cardiology at Duke University School of Medicine in Durham, North Carolina.
“The present study has interesting implications for the impact of weight regain that may occur after pharmacologic therapies,” they write. “What is still unknown is whether these temporary improvements in weight and cardiometabolic risk factors after weight loss intervention (behavioral or pharmacological) lead to long-term clinical benefit. In other words, is it better to have lost and regained than never to have lost at all?”

In type 1 diabetes, the body does not produce insulin. This means that patients have to obtain the hormone externally to regulate their blood sugar levels. Nowadays, this is mostly done via insulin pumps that are attached directly to the body. These devices, as well as other medical applications such as pacemakers, require a reliable energy supply, which at present is met primarily by power from either single-use or rechargeable batteries.
Now, a team of researchers led by Martin Fussenegger from the Department of Biosystems Science and Engineering at ETH Zurich in Basel have put a seemingly futuristic idea into practice. They have developed an implantable fuel cell that uses excess blood sugar (glucose) from tissue to generate electrical energy. The researchers have combined the fuel cell with artificial beta cells developed by their group several years ago. These produce insulin at the touch of a button and effectively lower blood glucose levels much like their natural role models in the pancreas.
“Many people, especially in the Western industrialised nations, consume more carbohydrates than they need in everyday life,” Fussenegger explains. This, he adds, leads to obesity, diabetes and cardiovascular disease. “This gave us the idea of using this excess metabolic energy to produce electricity to power biomedical devices,” he says.
Fuel cell in tea bag format
At the heart of the fuel cell is an anode (electrode) made of copper-based nanoparticles, which Fussenegger’s team created specifically for this application. It consists of copper-based nanoparticles and splits glucose into gluconic acid and a proton to generate electricity, which sets an electric circuit in motion.
Wrapped in a nonwoven fabric and coated with alginate, an algae product approved for medical use, the fuel cell resembles a small tea bag that can be implanted under the skin. The alginate soaks up body fluid and allows glucose to pass from the tissue into the fuel cell within.
A diabetes network with its own power supply
In a second step, the researchers coupled the fuel cell with a capsule containing artificial beta cells. These can be stimulated to produce and secrete insulin using electric current or blue LED light. Fussenegger and his colleagues already tested such designer cells some time ago (see ETH News, 8 December 2016).
The system combines sustained power generation and controlled insulin delivery. As soon as the fuel cell registers excess glucose, it starts to generate power. This electrical energy is then used to stimulate the cells to produce and release insulin into the blood. As a result, blood sugar dips to a normal level. Once it falls below a certain threshold value, the production of electricity and insulin stops.
The electrical energy provided by the fuel cell is sufficient not only to stimulate the designer cells but also to enable the implanted system to communicate with external devices such as a smartphone. This allows potential users to adjust the system via a corresponding app. A doctor could also access it remotely and make adjustments. “The new system autonomously regulates insulin and blood glucose levels and could be used to treat diabetes in the future,” Fussenegger says.
A long, uncertain road to market maturity
The existing system is only a prototype. Although the researchers have successfully tested it in mice, they are unable to develop it into a marketable product. “Bringing such a device to market is far beyond our financial and human resources,” Fussenegger says. This would call for an industry partner with the appropriate resources and know-how.

Fibroblasts build and maintain the extracellular matrix, or physical scaffolding for cells, in the connective tissues within the body. It is believed that cancerous tumors can recruit nearby fibroblasts and use them to promote their own growth and invasion. This process, called cancer-associated fibroblast activation, can also protect tumors from chemotherapy and make treatment difficult.
In APL Bioengineering, by AIP Publishing, researchers from Academia Sinica, National Yang Ming Chiao Tung University, National Taiwan University Hospital, and National Taiwan University developed a 3D cell culture system to test how inhibiting fibroblast activities can help treat lung cancer. They found that combining the anti-fibrotic drug nintedanib with the anti-cancer drug cisplatin increased the efficacy of the latter.
“Nearly 90% of late-stage lung cancer patient deaths are caused by the spread of tumors to other organs, rather than the primary tumor,” said author Chau-Hwang Lee. “Therefore, it is crucial to find ways to inhibit lung cancer metastasis to prolong the lives of lung cancer patients.”
To simulate the tumor microenvironment and mimic real tissues, the team co-cultured lung cancer cells and fibroblasts in a 3D matrix. The cancer cells formed a spheroid, around which the fibroblasts were randomly distributed.
The researchers tested the anti-cancer drug cisplatin with and without two anti-fibrotic drugs, nintedanib and pirfenidone. They measured indicators of tumor growth and invasiveness, finding that nintedanib improved the anti-cancer efficacy of cisplatin. Pirfenidone did not show a similar effect.
“Our results suggest that the combination of nintedanib and cisplatin could be an effective treatment strategy for lung cancer by targeting both cancer cells and cancer-associated fibroblast activation surrounding the tumor,” said Lee.
The 3D cell culture system will be a valuable tool for assessing the efficacy of other drug combinations on tumor growth and invasion. It could eliminate the need for animal testing while still reliably evaluating drug efficacy and safety.
“This study could pave the way for the development of more effective treatment strategies for lung cancer and other solid tumors,” said Lee. “It is our hope that this study will introduce a new, promising tool for preclinical drug testing.”
The authors plan to study other types of cancers, such as liver and oral cancer, using the same system. They also hope to improve the culture to better mimic the tumor microenvironment.