Using ultrasound to attack oral cancer cells

 

Peer-Reviewed Publication

Indian Institute of Science (IISc)

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Ultrasound mechanostimulation-mediated killing of oral cancer cells and compromised integrity of the capsule-like barrier

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Credit: Rashmita Luha

Oral cancer is a major health challenge in India, where tobacco and areca nut use contribute substantially to the disease burden. Despite advances in surgery, chemotherapy, and radiotherapy, treatment remains difficult because current approaches can damage healthy tissues along with cancer cells, often affecting patients’ quality of life.

In a new study, researchers at the Indian Institute of Science (IISc), in collaboration with clinicians at MS Ramaiah Medical College and Hospitals, explored whether low-frequency ultrasound mechanical stimulation could selectively kill oral cancer cells. The team worked with patient-derived oral tumour samples that better reflect variations among Indian patients.

The team found that oral cancer cells are surprisingly vulnerable to the moderate mechanical stimulations produced by ultrasound. This vulnerability appears to arise from reduced levels of Tropomyosin 2.1, a mechanosensory protein that helps body cells sense and withstand physiologically relevant mechanical stimulation. When exposed to ultrasound-driven mechanical stimulation, oral cancer cells underwent selective cell death, while healthy oral epithelial cells remained unharmed.

“The novelty of this study lies in showing how ultrasound mechanostimulation can selectively target oral cancer cells by exploiting their mechanical weakness,” says Ajay Tijore, Assistant Professor at the Department of Bioengineering, IISc, and corresponding author. “Instead of using heat or drugs, this approach uses moderate mechanical forces to damage cancer cells beyond their ability to recover.”

The team also found that ultrasound drastically reduces the cancer cells’ ability to migrate and invade surrounding tissue. Intriguingly, using a 3D co-culture platform that mimics the oral tumour microenvironment, the team found that ultrasound disrupted the dense capsule-like barrier formed by cancer-associated cells around the tumour core. Such barriers prevent drugs and immune cells from reaching the tumour core, resulting in treatment failure.

“What surprised us most was the consistency of the response across cancer cells derived from multiple patients from different cancer stages. They were highly vulnerable to ultrasound, while normal cells were much less affected,” says Rashmita Luha, PhD student in the Department of Bioengineering and first author.

Since ultrasound is non-invasive and already approved for various medical uses, these findings suggest that ultrasound mechanostimulation could exploit the mechanical weakness of oral cancer cells. With further validation in advanced preclinical models, this approach may help develop safer, more targeted treatment strategies for oral cancer and potentially other easily accessible cancers such as breast and skin cancers.

“The clinical collaboration was very important because it allowed us to work with patient-derived oral tumour samples rather than relying only on standard cell lines developed in Western countries,” says Tijore. “In the future, we want to test this approach in more physiologically relevant models and explore whether ultrasound can be combined with existing treatments to improve drug penetration and therapeutic outcomes.”

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Journal

Materials Today Bio

DOI

10.1016/j.mtbio.2026.103375 

Bleeding gums and kidney disease? Study uncovers a surprising link

Researchers found that severe periodontitis was associated with poorer kidney health and increased albuminuria in adults

Peer-Reviewed Publication

Editorial Office of West China School of Stomatology, Sichuan University

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Mediation analysis of the association between periodontitis and kidney function, showing that systemic inflammation partially mediates the link between periodontitis, estimated glomerular filtration rate, and albuminuria

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Credit: University Medical Center Hamburg-Eppendorf, Dr. Christian Schmidt-Lauber, and Prof. Dr. Ghazal Aarabi Image link: https://doi.org/10.1038/s41368-026-00435-6

Periodontitis is often viewed as a disease limited to the oral cavity, characterized by bleeding gums, progressive tissue destruction, and eventual tooth loss. However, growing evidence suggests that its impact may extend well beyond the mouth. The chronic inflammatory burden associated with periodontitis has been linked to several systemic conditions, including cardiovascular disease and diabetes, prompting researchers to investigate its potential role in chronic kidney disease (CKD). Although previous studies have reported associations between periodontitis and advanced CKD, whether this relationship is already present during the early stages of kidney dysfunction remains less clear.

To address this question, researchers from the University Medical Center Hamburg-Eppendorf, led by Dr. Christian Schmidt-Lauber and Prof. Dr. Ghazal Aarabi, conducted a large population-based study examining the relationship between periodontal disease and early markers of kidney impairment. Dr. Schmidt-Lauber, explains the motivation behind the study, “We aimed to evaluate the relationship between periodontitis and markers of early kidney dysfunction, including reduced renal function and albuminuria, and to explore the potential mediating role of systemic inflammatory markers.” The findings were published in Volume 18 of International Journal of Oral Science on April 6, 2026.

The study included 6,179 participants from the Hamburg City Health Study, a population-based cohort in Germany. All participants underwent detailed periodontal examinations, with disease severity classified according to the 2017 American Academy of Periodontology/European Federation of Periodontology (AAP/EFP) staging system. Kidney health was assessed using estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (uACR), while circulating levels of high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) were measured to evaluate the contribution of systemic inflammation.

The analysis revealed a consistent association between poorer periodontal health and worsening kidney function. The prevalence of severe periodontitis increased from 14% among individuals with normal kidney function to 36% among those with moderately reduced kidney function. A similar pattern was observed for albuminuria, with more advanced periodontal disease becoming increasingly common as urinary albumin levels rose. Measures of cumulative periodontal damage, including clinical attachment loss and tooth loss, also worsened across stages of kidney dysfunction.

Notably, these associations persisted after adjustment for major confounding factors such as age, sex, diabetes, and smoking status. Severe periodontitis remained independently associated with lower eGFR and higher uACR, while greater clinical attachment loss was linked to both declining kidney function and increased albuminuria. These findings suggest that the observed relationship is not simply the result of shared risk factors.

Systemic inflammation appeared to contribute to the association, but only partially. Levels of hsCRP and IL-6 increased with both worsening periodontal disease and declining kidney health. However, mediation analyses indicated that hsCRP accounted for approximately 35% of the association between severe periodontitis and reduced eGFR, and only about 10% of the association with albuminuria. These results imply that additional biological mechanisms may be involved, including microbial dissemination from periodontal tissues, endothelial dysfunction, oxidative stress, and metabolic alterations.

Because CKD frequently progresses without symptoms until substantial kidney damage has occurred, identifying early indicators of risk remains a major clinical challenge. “By demonstrating an association between periodontitis and markers of early kidney dysfunction, this study highlights oral health as a potential window into kidney health,” shares Prof. Dr. Aarabi. The findings may inform future screening approaches and provide a rationale for interventional studies investigating whether periodontal treatment can help preserve renal function. The study’s large sample size, standardized periodontal assessments, and comprehensive evaluation of kidney biomarkers further strengthen the reliability of the results.

In conclusion, the study provides strong evidence that periodontitis is independently associated with reduced kidney function and increased albuminuria, even at early stages of CKD. While systemic inflammation appears to explain part of this relationship, much of the association likely involves additional biological pathways. Together, these findings reinforce the growing recognition that oral and kidney health are closely interconnected and underscore the importance of considering periodontal disease within the broader context of systemic health.

 

Reference

Biology underlying oral health issues in Down syndrome

Researchers at NYU College of Dentistry have uncovered what may be biologically driving oral health issues unique to Down syndrome.

Their study, published in Cell Reports, describes a molecular mechanism—a defect in calcium signaling—behind low saliva production, along with other factors that may contribute to gum disease.

“Understanding the processes responsible for low saliva in Down syndrome and developing therapies to restore salivation could have a transformative impact on the oral and overall health of people with Down syndrome,” said Rodrigo Lacruz, professor of molecular pathobiology at NYU College of Dentistry and the study’s senior author.

A challenge to oral health

Down syndrome is a common genetic disorder that results in intellectual differences and physical issues, including an increased risk for hearing loss and heart disease. It's less well-known that the majority of those with Down syndrome have gum disease—around 60-90 percent of individuals under the age of 35, a rate that far exceeds that of people without Down syndrome, including those with other intellectual disabilities.

“Of the diverse health challenges that individuals with Down syndrome face, their higher risk of oral disease remains largely unexplored,” said Ga-Yeon Son, a senior research scientist in the Department of Molecular Pathobiology at NYU College of Dentistry and the study’s first author. “While dietary and oral hygiene factors may contribute to dental issues in some with Down syndrome, we observed changes in saliva, calcium signaling, and the microbiome, all of which could contribute to poor oral health.”

Studies increasingly show that people with Down syndrome produce less saliva, a condition known as hyposalivation. Hyposalivation can alter the oral microbiome—the balance of microbes in the mouth—and increase infection-causing bacteria that promote gum disease and tooth decay. This greater risk of gum disease, in turn, increases the risk of other health issues, including Alzheimer’s disease, which occurs in most people with Down syndrome as they age.

Altered signals, microbiome

To gain a deeper understanding of oral health biology in Down syndrome, the researchers studied a widely used mouse model of the genetic disorder. They found several changes to the mice’s saliva that mirror what studies show in people with Down syndrome: they produce much less saliva, but the saliva is more acidic and contains elevated levels of certain immune markers.

Notably, store operated calcium entry—a calcium signaling process required for saliva secretion—was decreased in the mice’s salivary glands.

“This dysfunction in calcium signaling is likely responsible for hyposalivation in Down syndrome,” said Lacruz. “Decreased saliva flow can have systemic consequences, advancing periodontal disease and impacting the microbial ecosystem."

Additional analyses showed high levels of inflammatory markers in gum tissue and increased inflammation as well as decreased mitochondrial function in the salivary glands.

“Altered mitochondrial function has been widely reported in individuals with Down syndrome.  What is particularly compelling about these studies is that they provide evidence of a pathway through which changes in mitochondrial function and calcium handling in salivary glands may be having a system-wide impact on the health of individuals with Down syndrome,” said Beverly Rothermel, a study author and professor at UT Southwestern Medical Center.

The researchers also discovered certain autoantibodies in the mice that are used to diagnose Sjögren’s disease, an autoimmune condition marked by low saliva production. Through additional tests, they found hints that those with Down syndrome may be at increased risk for Sjögren’s.

Looking beyond the mouth, the researchers studied the blood and gut microbiome of the mice with Down syndrome. The mice had high levels of succinate—a metabolic byproduct linked to inflammation and gum disease—in their blood, as well as succinate-producing bacteria in the gut and mouth.

“This systemic alteration of succinate and changes to the oral and gut microbiome appear to be influencing the biology of Down syndrome,” said study author Deepak Saxena, professor of molecular pathobiology and director of research innovation and entrepreneurship at NYU College of Dentistry. “While more research is needed to understand how these differences influence one another—and ultimately drive hyposalivation and gum disease—the findings provide clues about the unique oral health challenges in this population.”

A path toward treatment

According to the researchers, addressing oral health for individuals with Down syndrome could include efforts to both improve oral hygiene—for instance, more frequent dental visits or implementing practices in group homes related to diet and toothbrushing—and treat the underlying biological factors.

People who experience dry mouth due to Sjögren’s or who have undergone radiation for head and neck cancer are often prescribed pilocarpine, a medication that stimulates saliva and tear production and appears on the World Health Organization’s Essential Medicines List. The researchers found that giving pilocarpine to mice with Down syndrome increased salivation.

“Targeting hyposalivation to boost saliva production could potentially improve some of the systemic disruptions that individuals with Down syndrome experience. This is our next research focus,” said Lacruz.

Additional study authors include Guilherme H. S. Bomfim, Fangxi Xu, Scott C. Thomas, Kristen Rosenberg, Tommy Kim, Eleni Rice, Enkhnaran Budjab, Rebecca Jones, Yin-Hu Wang, Erna Mitaishvili, Stefan Feske, Drew R. Jones, and Edwin Rosado-Olivieri of NYU. The research was supported by the National Institute of Dental and Craniofacial Research (NIDCR) (DE032846), National Institute of Allergy and Infectious Diseases (AI80128), and NYU Academic Enhancement Funds.

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Journal

Cell Reports

DOI

10.1016/j.celrep.2026.117619 

Postbiotic foods for improving gum health

Foods containing heat-inactivated bacteria help reduce gum bleeding and improve inflammatory conditions

Peer-Reviewed Publication

Institute of Science Tokyo

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Foods containing  heat-inactivated Lactiplantibacillus pentosus can help prevent gingivitis and maintain oral health.

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Credit: Institute of Science Tokyo (Science Tokyo), Japan

Continuous consumption of foods containing heat-inactivated Lactiplantibacillus pentosus can help reduce gum bleeding, report researchers from Institute of Science Tokyo. These postbiotic foods can improve inflammatory conditions and enhance gum health in adults with mild gingivitis. The study suggested that these postbiotic foods offer a simple and practical way to support oral health in daily life without altering oral care habits. The findings also aid in the prevention of early-stage periodontal disease.

Gum disease, also known as periodontal disease, affects millions of people worldwide. In early stages, known as gingivitis, the gums become swollen and are prone to bleeding. While professional dental care and regular oral hygiene is important for prevention of the disease, researchers are exploring innovative approaches that can support gum health in everyday life. One promising strategy is the use of probiotic (beneficial bacteria) for maintaining gum health. However, these usually disturb the natural balance of microorganisms in the oral cavity. Also, these probiotics possess a shorter shelf life and are less stable.

Addressing this issue, a research team led by Professor Takanori Iwata along with Assistant Professor Shogo Maekawa, and Visiting Lecturer Anhao Liu from the Department of Periodontology, Institute of Science Tokyo (Science Tokyo), Japan, in collaboration with Associate Professor Megumi Ishiguro of the Health Science Research and Development Center, Science Tokyo, Otsuka Pharmaceutical Co., Ltd., and Tokyo Center Clinic, Japan, investigated if postbiotic foods containing heat-inactivated bacteria (Lactiplantibacillus pentosus ONRICb0240) could help improve gum health and reduce bleeding without disrupting normal oral bacteria. The findings were published online in the Journal of Periodontology on April 19, 2026.

“We conducted a clinical trial on 116 adults who were suffering from mild gingival inflammation,” explains Iwata. The participants were randomly allocated to receive either the gummies containing heat-inactivated bacteria or placebo (non-loaded) gummies. The gummies were consumed twice daily for six weeks. The participants were not given any special instructions regarding tooth brushing or additional oral care, which allowed the researchers to evaluate the effectiveness of the gummies under realistic conditions.

At the end of the study, the researchers evaluated the gum health and gingival index (a measure of gum inflammation) of the participants. Surprisingly, the participants who had consumed the postbiotic gummies experienced less gum bleeding and their gums appeared healthier and stronger overall, compared to those who received the placebo gummies. For the gingival index, no significant difference was observed between the groups; however, a significant improvement from baseline was observed in the test group.

“By evaluating the gummies under normal daily living conditions, we were able to better understand their practical potential for supporting gum health,” says Iwata.

The significance of the study lies in the use of heat-inactivated bacteria rather than live probiotics strains. Heat-inactivated bacteria are generally more stable during manufacturing and storage, making them easier to convert into consumer products than live bacteria. In addition to this, the researchers believe that the anti-inflammatory effects of the postbiotic gummies might be responsible for the reduction in gum bleeding. Since gum bleeding is one of the earliest warning signs of gingivitis, reducing inflammation at this stage could help prevent the progression to more serious periodontal disease.

Overall, the research provides a simple and convenient method that can be added to routine oral care practices. It also highlights the growing potential of functional foods and probiotic-derived ingredients in preventive healthcare. Looking ahead, the researchers plan to investigate the underlying biological mechanisms and evaluate the long-term benefits of these gummies for periodontal health.

Fasting-mimicking diet reduces gum disease inflammation

 

People who follow a short-term low-calorie diet may have reduced markers of inflammation associated with gum disease.

Peer-Reviewed Publication

King's College London

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People who follow a short-term low-calorie diet may have reduced markers of inflammation associated with gum disease.

A new study by King’s College London highlights how lifestyle modifications could be important alongside plaque control in managing gum disease.

While fasting has been linked to reduced inflammation around the body, this is the first to establish a relationship with gum disease too. The findings offer new insights into how oral and wider body health are closely intertwined.

Dr Giuseppe Mainas, first author of the study, King’s College London, said: “Our study suggests lifestyle modifications could be important alongside proper tooth brushing for patients.”

Periodontitis, a serious form of gum disease, affects millions of people worldwide and has been linked to wider health problems, including heart disease and diabetes. While standard treatment focuses on cleaning infected areas around the teeth, researchers are increasingly exploring whether diet can play a role in improving outcomes.

The research included 28 patients from across hospitals in Spain, split into two groups – those who followed a five-day restrictive diet, versus a control group who continued their usual diet.

Patients who fasted ate 1,100 calories for two days, then 750 calories for three days. The sixth day gently introduced more calories with soft foods – then their diets returned to normal by the seventh day. This was repeated three times in six months, with patients reporting the diet easy to stick to.

After six months, samples were analysed from the patients’ blood and gingival crevicular fluid – liquid that comes from the small space between your tooth and gum, which helps gums stay healthy and fight germs.

Those who fasted had reduced markers of inflammation in samples from blood and gum tissue compared to those whose diets stayed the same, including lower levels of C-reactive protein, a general indicator of inflammation around the body. The fasting group also had reduced molecules linked to inflammation specifically in the gums, compared to controls.

Senior-author Prof Luigi Nibali, King’s College London, said: “There may be multiple reasons why fasting is beneficial to gum disease patients. Fasting reduces oxidative stress in the body, a common cause of inflammation, which can damage cells and DNA.

“Intake of high calorific foods and refined carbohydrates, for example in cakes and biscuits, can also cause inflammation – so restricting these foods also reduces oxidative stress in the body.

“It may also be that fasting has beneficial effects on the microbiome – the body’s community of bacteria that help to keep it healthy. However, further research is needed to confirm this relationship.”

Dietary approaches such as fasting-mimicking diets could be investigated in the future as supporting approaches alongside conventional therapies for gum disease, such as professional cleaning and oral hygiene support.

Dr Mainas added: “Now we have established this relationship, we would like to do a larger study, before potentially incorporating into gum disease treatment in the future. There may be patients where restricting foods can be dangerous, such as those with diabetes, so the advice will need to be targeted to specific patient groups. We are currently investigating how we could implement these benefits in high-risk groups who may not be able to fast.”

The study builds on long-standing research by King’s College London investigating the relationship between gum disease and wider health. Last year, researchers at King’s discovered following the mediterranean diet reduces gum disease, and that successful dental treatment reduces risks of diabetes and heart disease.

This study was published in Journal of Clinical Periodontology (JCP).

Diabetes is associated with tooth and implant loss

 

Reports and Proceedings

University of Gothenburg

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Anna Trullenque Eriksson, Sahlgrenska Academy at the University of Gothenburg.

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Credit: Photo: Majk Zanqrelle)

Persons with diabetes have an increased risk of periodontitis (gum disease) and tooth loss. The risk of inflammation and bone loss at dental implants was also higher. These are the findings of a thesis at the University of Gothenburg.

Diabetes is associated with complications in multiple organs, including the oral cavity. As a group, persons with type 1 or type 2 diabetes are at higher risk for oral diseases.

This thesis is based on a comprehensive dataset from seven Swedish registers covering a long time period, with a high degree of completeness. The thesis was presented by dentist Anna Trullenque Eriksson, who specializes in periodontology.

The thesis addresses the link between the systemic condition diabetes and the oral conditions periodontitis, tooth loss and peri-implantitis (an inflammatory disease in the tissues surrounding dental implants). Compared with previous studies, the study sample is strikingly large, particularly for type 1 diabetes. 

Glycemic control matters

Persons with type 1 diabetes and poor control of blood sugar levels were found to have an increased risk of periodontitis and tooth loss, compared to matched controls without diabetes. However, no such differences were evident for those with continuously good glycemic control.

In the case of type 2 diabetes, the risk of periodontitis and tooth loss was elevated, regardless of blood sugar control. The correlation was strongest when glycemic control was poor. In turn, periodontitis was linked to an increased risk of diabetes-related eye and kidney complications in both diabetes types.

Among individuals with dental implants, those with type 1 or type 2 diabetes were at higher risk of peri-implantitis and implant loss. Poor blood sugar control was a key factor for poor implant outcomes.

The risk of complete tooth loss was particularly high among persons with diabetes who were also socio-economically disadvantaged (lower income, shorter education), highlighting the importance of socioeconomic factors. Data from both Sweden and Denmark were considered.

Important to be aware of the risks

The thesis reinforces previous evidence of a link between diabetes and oral diseases and stresses the importance of close collaboration between health care and dental care providers. The findings on dental implants are novel, suggesting that diabetes may affect long-term outcomes of implant therapy.

“Within the dental community, most are aware of the link between diabetes and impaired oral health. Our data support the notion that dental care should be part of diabetes prevention strategies,” states Anna Trullenque Eriksson.

Thesis: Periodontal research using nationwide registry data, https://hdl.handle.net/2077/90395

Fact box: Tooth loss and diabetes

Type 1 diabetes (analyses based on 86,273 individuals; mean age 43 years)

• 33.9% had lost one or more teeth over a 10-year period (25.3% among those with good glycemic control; 43.5% among those with poor control). Among matched controls without diabetes 29.0% experienced tooth loss.
• 3.1% had lost five or more teeth over ten years (good control: 1.0%; poor control: 5.6%). The corresponding figure for controls was 1.9%.

Type 2 diabetes (analyses based on 786,305 individuals; mean age 60 years)

• 46.1% had lost one or more teeth over a 10-year period (44.0% among those with good glycemic control; 54.9% among those with poor control). Among matched controls without diabetes 37.8% experienced tooth loss.
• 7.0% had lost five or more teeth over ten years (good control: 5.7%; poor control: 12.6%). The corresponding figure for controls was 3.7%.