MMP8

PHILADELPHIA, Jan. 7, 2025 /PRNewswire/ -- Measuring levels of key proteins in patients' saliva may be a relatively easy way for dentists and even patients themselves to track the progression of gum disease (periodontitis), suggests a new study led by Penn Dental Medicine researchers. In the study, the researchers monitored and tested saliva samples from more than 400 patients for up to a year and a half. They found that on average, patients with moderate to severe progression of periodontitis showed substantial increases in nine inflammation-related signaling proteins in saliva. The study appears in the December Journal of Clinical Periodontology, a 50th anniversary edition that showcases particularly high-quality research. "One can imagine a saliva test kit, based on such findings, that dentists could use and even periodontitis patients could use at home—it could be a very useful personalized-dentistry tool for assessing risk and tailoring care," says study lead author Flavia Teles,DDS, MS, DMSc, Associate Professor, Department of Basic & Translational Sciences, at Penn Dental Medicine. Between 20 and 50 percent of the global population have some level of periodontitis, including about 64 million people in the U.S. If untreated, this chronic bacterial infection and inflammation of gums often leads to the loss of the bone that anchors teeth, which can cause tooth loss. This study enrolled 302 individuals with early to moderate/severe periodontitis, and 113 individuals without periodontitis. Subjects' periodontitis status and progression were assessed every two months for a year. They also had saliva and blood samples taken; the saliva samples were tested for 10 inflammation-linked proteins, and the blood samples for five. After a year, researchers gave periodontitis subjects standard non-surgical periodontal therapy and checked them again three and six months later. The results showed that periodontitis patients who had the most disease progression during the year had significantly higher levels of several inflammation-related signaling proteins in their saliva. These included interferon-gamma, IL-6, VEGF, IL-1β and MMP-8. Following treatment, these levels subsided. The levels of such proteins in subjects' blood did not differ significantly by degree of disease progression, although MMP-8, MMP-9, and C-reactive protein, did fall significantly following treatment. The findings suggest that changes in levels of inflammation-related proteins in saliva over time can help assess the risk of periodontitis progression as well as treatment effectiveness —and that blood levels also may be helpful in the latter case. Contact: Beth Adams, [email protected] SOURCE PENN DENTAL MEDICINE WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Chronic stress affects the immune system and the brain. Researchers now show that a particular enzyme found in cells of the immune system enters the brain under stress. In mice, it causes them to withdraw and avoid social contact. This newly discovered connection between body and mind in stress-related mental illnesses could lead to new treatments for depression. Chronic stress affects the immune system and the brain. UZH researchers now show that a particular enzyme found in cells of the immune system enters the brain under stress. In mice, it causes them to withdraw and avoid social contact. This newly discovered connection between body and mind in stress-related mental illnesses could lead to new treatments for depression. Chronic stress has far-reaching consequences for our bodies. For example, many stress-related psychiatric illnesses such as depression are associated with changes in the immune system. However, the underlying mechanisms of how these changes affect the brain are still largely unknown. Enzyme from immune cells in the blood affects nerves in the brain An international research team led by the University of Zurich (UZH), and the University Hospital of Psychiatry Zurich (PUK) and the Icahn School of Medicine at Mount Sinai, New York, has now uncovered a novel mechanism. "We were able to show that stress increases the amount of the matrix metalloproteinase-8 (MMP-8), an enzyme in the blood of mice. The same changes were found in patients with depression," says first author Flurin Cathomas. MMP-8 travels from the blood to the brain, where it alters the functioning of certain neurons. In the affected mice, this leads to behavioral changes: they withdraw and avoid social contact. Potential for new treatments for depression According to Cathomas, the findings are novel in two respects: "Firstly, they indicate a new 'body-mind mechanism', which might be relevant not only for stress-related mental illness, but also for other diseases that affect both the immune and nervous systems." And secondly, says the psychiatrist, identification of the specific MMP-8 protein could be a potential starting point to develop new treatments for depression. Changes to brain extracellular matrix The researchers were able to use animal models to show that stress increases the migration of a specific type of white blood cells called monocytes into the vascular system of the brain, particularly into the reward center regions. These monocytes produce MMP-8. MMP-8 is involved in the restructuring and regulation of the net-like frame that surrounds neurons in the brain -- called the extracellular matrix. "If MMP-8 penetrates the brain tissue from the blood, it changes the matrix structure and thus disrupts the functioning of the neurons. Mice who are affected by this process display changes in behavior that are similar to those seen in humans with depression," says Flurin Cathomas. In order to prove that MMP-8 was really responsible for the behavioral changes, the researchers removed the MMP-8 gene from some of the mice. Compared to the control mice, these animals did not display stress-related negative behavioral changes. "Blood analyses of patients with depression indicate that the findings from the mouse models are also relevant for humans: both the monocytes and MMP-8 were increased in the blood of people with depression in comparison to healthy participants." Clinical studies with patients planned Many more studies are needed before the results can be implemented in clinical practice. Nevertheless, says Cathomas, "our work once again demonstrates the importance of the interaction between the immune system and the brain in the development of psychiatric disorders. These insights are already being incorporated into psychiatric treatment today." On the PUK's special ward for integrative care led by Cathomas, the clinicians take a holistic mind-body approach based on the latest scientific findings when treating their patients. The research team is now planning clinical studies to investigate the extent to which the immune system can be influenced by stimulating certain areas of the brain. They will also look at whether any changes in the immune system cells of depressive patients influence their behavior.

BACKGROUND. Gingivitis and periodontitis are prevalent inflammatory diseases of the periodontal tissues. Current treatments are often ineffective or do not prevent disease recurrence. Uncontrolled complement activation and resulting chronic gingival inflammation is a hallmark of periodontal diseases. We determined efficacy and safety of a complement 3-targeted therapeutic, AMY-101, locally administered in adults with periodontal inflammation. METHODS. Thirty-two patients with gingival inflammation were enrolled into a randomized, placebo-controlled, double-blind, split-mouth design phase 2a trial, after dose-escalation study to select safe and effective dose with additional 8 patients. Half of the mouth was randomly assigned to AMY-101 (0.1mg/site) or placebo injections at sites of inflammation, administered on days 0, 7 and 14 and evaluated for safety and efficacy outcomes at days 28, 60 and 90. The primary efficacy outcome was change in gingival inflammation, measured by modified gingival index (MGI), and secondary outcomes included changes in bleeding-on-probing (BOP), amount of plaque, pocket depth, clinical attachment level, and gingival crevicular fluid levels of matrix metalloproteinases (MMPs) over 90 days. RESULTS. A once-per-week intragingival injection of AMY-101 for 3 weeks was safe and well-tolerated in all participants resulting in significant (P<0.001) reductions in clinical indices measuring gingival inflammation (MGI and BOP). AMY-101 significantly (P<0.05) reduced MMP-8 and MMP-9 levels, indicators of inflammatory tissue destruction. These therapeutic effects persisted for at least 3 months post-treatment. CONCLUSION. AMY-101 causes significant and sustainable reduction in gingival inflammation without adverse events and merits further investigation for the treatment of periodontitis and other oral or peri-implant inflammatory conditions. TRIAL REGISTRATION. ClinicalTrials.gov: NCT03694444. FUNDING. Amyndas Pharmaceuticals. Amyndas contributed to the design and conducts of the clinical trial and in the writing of the manuscript. Hasturk H, Hajishengallis G, Lambris JD, Mastellos DM, Yancopoulou D. (2021). Phase 2a clinical trial of complement C3 inhibitor AMY-101 in adults with periodontal inflammation. J Clin Invest. [Online ahead of print].