Universidade Federal de São Carlos

Scientists have created an artificial saliva using a sugarcane protein that can protect teeth and fight bacteria. The key ingredient, CANECPI-5, binds directly to enamel, forming a shield against acids that cause decay. Early tests show it works even better when paired with fluoride and xylitol, significantly reducing damage to teeth. The innovation could be especially life-changing for cancer patients who lose saliva production after treatment.A new type of artificial saliva, delivered as a mouthwash and made using a lab-modified sugarcane protein called CANECPI-5, could help protect the teeth of patients with head and neck cancer. These patients often undergo radiotherapy near the mouth, which can damage salivary glands and reduce saliva production. Because saliva plays a key role in controlling bacteria and maintaining oral health, its loss can lead to serious dental problems. Researchers at the Bauru School of Dentistry at the University of São Paulo (FOB-USP) in Brazil found that CANECPI-5 creates a protective "shield" over teeth. This layer helps defend enamel from acids found in beverages like juice and alcohol, as well as acids from the stomach. The findings were published in the Journal of Dentistry. International Research Collaboration and Study Design The research was carried out during the doctoral work of Natara Dias Gomes da Silva at FOB-USP. The project included collaboration with scientists from the Federal University of São Carlos (UFSCar) in Brazil, the University of California in San Francisco in the United States, and Yonsei University College of Dentistry in South Korea. The study is part of the Thematic Project "Modulation of acquired pellicle to control dental mineral loss: unveiling mechanisms to make therapies possible," coordinated by Professor Marília Afonso Rabelo Buzalaf at FOB-USP. "We tested the mouthwash developed with CANECPI-5 by applying this solution to small pieces of animal teeth once a day for one minute. Based on these results, we'll conduct further research so that we can think about applications of this product," adds Silva, the first author of the article. How Artificial Saliva Strengthens Tooth Enamel "This is the first product that uses the concept of acquired pellicle [a thin protective layer that quickly forms on the tooth surface] to treat xerostomia, which is the sensation of a dry mouth caused by a lack of saliva. We use substances that will reformulate the composition of the proteins that bind to the teeth," explains Buzalaf. "We've developed a process in which CANECPI-5 binds directly to tooth enamel, helping to make teeth more resistant to the action of acids produced by bacteria," Silva points out. The study showed that CANECPI-5 works best when combined with fluoride and xylitol. In testing, the artificial saliva spray reduced bacterial activity and slowed tooth demineralization -- the process by which teeth lose calcium and phosphate, making them more vulnerable to cavities. A Potential Solution for Severe Cavities After Cancer Treatment This development is especially important because there is currently no dedicated product available to treat the severe cavities that often occur after radiation therapy for head and neck cancer. "Artificial saliva improves the sensation of dry mouth and sores. This helps with discomfort and also combats bacteria. In some cases, the use of this type of product is only for a short time. In others, it's permanent, because many individuals lose the ability to produce saliva," adds Buzalaf. The CANECPI-5 protein has already been patented. The next step is to scale up production by partnering with companies interested in bringing the technology to market. "We've already tested the solution as a mouthwash, gel, and orodispersible film, which is a type of plastic that's placed on the tongue and dissolves, releasing the protein. We've tested it in several vehicles and found that CANECPI-5 works very well in all of them. We'll continue testing other technologies within the Thematic Project to use not only this protein, but others as well," says Buzalaf. The Discovery of CANECPI-5 From Sugarcane Research According to Flávio Henrique Silva, a professor in the Department of Genetics and Evolution at UFSCar who helped develop CANECPI-5, the work stems from earlier research on cystatins (a family of proteins involved in various biological processes) conducted as part of the Sugarcane Genome Project (SUCEST, FAPESP). "At that time, our group identified and produced, in a recombinant form in bacteria, the first cystatin from sugarcane. We named it CANECPI-1. We then identified and produced five other cane cystatins, including CANECPI-5, which had potent inhibitory activities against cysteine peptidases, which are its target enzymes. Throughout our work, we noticed that this protein bound strongly to smooth surfaces, such as the quartz cuvettes used in activity measurements. This led us to conduct tests in partnership with Professor Marília Buzalaf on the binding of the protein to tooth enamel." Researchers say CANECPI-5 is especially promising because it both protects enamel and helps regulate oral bacteria, making it valuable for future dental treatments. "CANECPI-5 has also been used in the work of other colleagues in the field of dentistry, particularly involving periodontitis. We also have a collaborative project with a colleague from the Federal University of Uberlândia, using subcutaneous sponge implants in mice, which has shown that it's capable of reducing inflammation and promoting angiogenesis [the formation of new blood vessels] and fibrinogenesis [the formation of fibrin, a protein essential for blood clotting], important processes in tissue repair, making it a candidate molecule for use in wound healing," Silva points out. Next Steps for Artificial Saliva and Dental Applications Within the Thematic Project, researchers will continue exploring how CANECPI-5 interacts with other compounds. According to Buzalaf, one direction is to combine CANECPI-5 with a peptide derived from statherin, a protein found in saliva, to determine whether this hybrid could better protect teeth from acids originating in the stomach. Another goal is to investigate its potential role in preventing periodontal disease. "Another aspect of the Thematic Project is to associate CANECPI-5 with vitamin E because this vitamin acts as a carrier, bringing the protein into contact with the tooth. We imagine that this could facilitate the application of the product directly by the patient at home," says the researcher.

Having both excess belly fat and low muscle mass isn’t just unhealthy—it’s potentially deadly, raising the risk of death by 83%. This condition, called sarcopenic obesity, creates a vicious cycle where fat accelerates muscle breakdown and inflammation. Researchers found it can be identified using simple measurements, not costly medical tests. That means earlier detection—and a real chance to intervene before serious decline sets in.Researchers from the Federal University of São Carlos (UFSCar) in Brazil, working with University College London (UCL) in the United Kingdom, found that having both excess abdominal fat and reduced muscle mass significantly raises the risk of death. People with this combination were 83% more likely to die than those without either condition. This pairing points to a more serious underlying issue known as sarcopenic obesity. It occurs when muscle mass declines while body fat increases. The condition can be difficult to identify and is closely tied to reduced independence and poorer quality of life in older adults. It is also associated with frailty, a higher risk of falls, and other health complications. "In addition to assessing the risk of death associated with abdominal obesity and low muscle mass, we were able to prove that simple methods can be used to detect sarcopenic obesity. This is important because the lack of consensus on diagnostic criteria for this disease makes it difficult to detect and treat," says Tiago da Silva Alexandre, a professor in the Department of Gerontology at UFSCar and one of the study's authors, which was supported by FAPESP. "Thus, our findings allow older adults to have greater access to early interventions, such as nutritional monitoring and physical exercise, ensuring an improvement in quality of life." The findings were published in Aging Clinical and Experimental Research and are based on 12 years of data from 5,440 participants aged 50 and older in the English Longitudinal Study of Ageing (ELSA). Simple Screening May Replace Costly Tests Diagnosing sarcopenic obesity usually requires advanced imaging tools such as magnetic resonance imaging, computed tomography, electrical bioimpedance, or densitometry. These methods can accurately measure body fat and muscle mass, but they are expensive and not widely available, making routine diagnosis difficult. "By correlating data from ELSA study participants, we found that simple measures, such as measuring abdominal circumference and estimating lean mass [using a consolidated equation that considers clinical variables such as age, sex, weight, race, and height], showed for the first time that it's possible to screen these individuals early," Alexandre celebrates. Why the Combination Is Especially Dangerous Losing muscle while gaining abdominal fat has a compounded effect on the body's metabolism. "The study revealed that individuals with both conditions had an 83% higher risk of death compared to those who didn't have them. We also found that the risk of death was reduced by 40% among those with low muscle mass and no abdominal obesity, a finding that reinforces the potential danger of the coexistence of the conditions. Interestingly, individuals with abdominal obesity but adequate muscle mass weren't associated with an increased risk of death," explains Valdete Regina Guandalini, a professor at the Federal University of Espírito Santo (UFES) and researcher in the Department of Gerontology at UFSCar. She is also the first author of the article. According to Guandalini, excess fat worsens inflammation in the body, triggering metabolic changes that accelerate muscle breakdown. "In addition to one condition interfering with the other, fat infiltrates the muscle and takes up its space. This systemic and progressive inflammation directly affects muscle tissue, compromising its metabolic, endocrine, immunological, and functional capabilities," she says. Clearer Definitions Using Simple Measurements Because researchers around the world have not agreed on a single definition of sarcopenic obesity, the team used practical criteria to identify those at risk. Abdominal obesity was defined as a waist circumference greater than 102 centimeters for men and 88 centimeters for women. Low muscle mass was defined as a skeletal muscle mass index below 9.36 kg/m2 for men and below 6.73 kg/m2 for women. These simpler measures could make it easier to identify sarcopenic obesity earlier, helping more people access interventions that may reduce risk and improve long-term health.

研究发现USP30酶过度激活会抑制泛素标记缺陷线粒体，导致突变线粒体DNA逃逸"质量控制系统"并遗传给后代；使用化合物CMPD39抑制USP30可在受精后创造"清除窗口"，有效清除突变线粒体DNA。 发表于《科学》杂志的一项研究揭示了遗传突变传递的一种细胞机制，并指出一种潜在治疗方法，或可降低婴儿罹患严重且无法治愈的线粒体疾病的风险。 这项研究发现USP30酶过度激活会抑制泛素标记缺陷线粒体，导致突变线粒体DNA逃逸"质量控制系统"并遗传给后代；使用化合物CMPD39抑制USP30可在受精后创造"清除窗口"，有效清除突变线粒体DNA。这些发现为预防线粒体疾病提供了药理学治疗新思路。 根据研究结果，这些突变的传递涉及一个过程：该过程既阻止了突变线粒体的清除，同时又增加了它们在细胞中的数量。这解释了这些突变是如何"逃过"筛选并可能在将来引发疾病的。 线粒体是所有细胞的主要能量来源，并拥有自己的DNA。受精后不久，胚胎会启动一个"质量控制"系统来清除"有缺陷的"线粒体，该过程称为线粒体自噬。在此过程中，泛素蛋白作为一种标记物，指引被改变的分子走向销毁。 线粒体自噬维持着线粒体DNA与核DNA之间的和谐，确保两者的兼容性。然而，由于mtDNA的突变率比核基因组高出约15倍，这对它们的共生关系构成了挑战。 USP30酶通过阻断泛素并阻止其"标记"发挥作用，从而减少了（线粒体的）清除。USP30的失衡与多种疾病有关，包括线粒体疾病和神经退行性疾病。突变的大量积累会导致不相容，引起线粒体功能障碍并对健康产生负面影响。这一过程在科学文献中已有充分记载。 然而，一些较温和的突变同样会引起疾病，却被细胞忽视而未被清除。这一复杂机制此前人们知之甚少。 研究结果 研究人员现已在体内证明，细胞通过使泛素的标记效应失活来应对mtDNA突变，而不是激活新的生物合成途径。 科学家们利用小鼠发现，在受精后的头几天，突变并未被感知，因为USP30被过度激活，从而抑制了泛素标记有缺陷的线粒体DNA并阻断其清除。这导致线粒体质量和基因组的增加，使得能够引起疾病的突变得以传递。 研究中，研究小组证实，使用抑制剂化合物CMPD39阻止USP30发挥作用，可以在受精后不久为发生改变的线粒体DNA创造一个"清除窗口"。在此期间，胚胎会自然清除父系线粒体。与核DNA（孩子从父母双方各继承一半）不同，mtDNA仅由母亲传递。 在研究中，科学家提出了两种可能性：在体外受精后对早期胚胎进行处理，以在植入前减少具有高突变负荷的细胞数量；以及通过靶向USP30进行治疗，以治疗或预防影响约八千分之一的罕见遗传病。 该文章的通讯作者、剑桥大学神经病学教授Patrick Chinnery表示："线粒体疾病可能导致毁灭性的残疾，甚至阻止一些家庭生育孩子。英国已批准一种新的体外受精形式来防止其传播，但除此之外，我们无法预防这些疾病，而且可用的治疗方法也很少。我们的发现指出了一种可能的新的药物疗法，将来可能有助于阻止这些疾病，让家庭能够拥有健康的孩子。" 最近，纽卡斯尔大学的一个研究团队成功实施了一项创新的体外受精技术，该技术涉及用健康捐赠者的线粒体替换母亲的突变线粒体DNA。该治疗被称为线粒体替代疗法。已有八名婴儿——四男四女出生，他们可能受到保护而免于线粒体疾病。该结果发表在《新英格兰医学杂志》上。 该文章唯一的巴西作者、圣卡洛斯联邦大学遗传学与进化系教授Marcos Roberto Chiaratti补充说："我们知道这种涉及线粒体替代的技术存在争议，并且目前仅在英国和澳大利亚获得批准。通过我们的研究，我们表明还存在其他可能性，主要是药理学方面的，来治疗胚胎并预防此类疾病的传播。" 线粒体疾病是什么？ 线粒体疾病是影响线粒体功能的遗传性代谢紊乱，可能导致大脑和心脏等重要器官的损害。最常见的包括莱伯遗传性视神经病变、Leigh综合征和MELAS（线粒体脑肌病、乳酸酸中毒和卒中样发作）。 根据受影响的细胞不同，症状可能包括生长问题和认知发育迟缓，到肌肉无力、疼痛、视力/或听力丧失以及癫痫发作。 尽管这些疾病没有特效治疗方法，但有时会使用药物来控制症状。诊断通常很复杂，需要详细分析患者的临床数据，以及其他类型的检查，例如肌肉活检、生化分析和基因分子检测。（生物谷Bioon.com） 参考文献： Michele Frison et al, Ubiquitin-mediated mitophagy regulates the inheritance of mitochondrial DNA mutations, Science (2025). DOI: 10.1126/science.adr5438.