Every day, often hidden from notice, our bodies are locked in a constant\ntug-of-war between \u2018firefighters\u2019 and \u2018fires\u2019. The human immune system, acting\nas a well-trained fire brigade, springs into action the moment it detects\nabnormal fire hazards in the body. However, when the immune system becomes\noveractive, it can spark uncontrolled fires, leading to chronic inflammation.\nFrom skin redness and itching to joint pain and even cancer recurrence, these\ninflammation-related problems can spread like wildfire, threatening our health.\nAt the University of Macau (UM), research teams have taken on the role of\n\u2018immune firefighters\u2019, working to find innovative ways to extinguish these\nfires. Unlike traditional treatments that only manage inflammation symptoms or\ncome with unwanted side effects, the work of these researchers focuses on\naddressing the root causes of inflammation, providing better protection for\nhuman health.<\/p>\n\n
Rescue for Uncontrolled Skin Inflammation<\/p>\n\n
Skin inflammation is an increasingly common health concern in urban\nareas. According to statistics from Zhiyan Consulting Group in China, nearly\none in ten people in the country suffer from dermatitis, with over 70 million\naffected by eczema. Many patients experience such intense itching that it\ndisrupts their sleep, and some even scratch their skin until it bleeds, leading\nto infections and a loss of self-esteem. Traditional steroid treatments can\ncome with serious side effects. While biologics are effective, they are\nexpensive, with annual treatment costs reaching RMB 10,000, making them\nunaffordable for many families.<\/p>\n\n
Thanks to groundbreaking research at UM, a breakthrough may be on the\nhorizon. Prof Leung Chung Hang, professor in the Institute of Chinese Medical\nSciences (ICMS), and his research team have discovered a key mechanism behind\nskin inflammation\u2014a \u2018protein switch\u2019 called Keap1-Nrf2. The Nrf2 protein plays\na crucial role in directing cells to fight inflammation and maintain skin\nhomeostasis. However, during inflammation, the Keap1 protein \u2018kidnaps\u2019 Nrf2,\nshutting it down and allowing the inflammation to escalate, similar to a fire\nthat grows more intense over time.<\/p>\n\n
Previous attempts to treat inflammation focused on directly activating\nNrf2. However, this approach was much like a random guess at a password,\nrisking interference with other physiological functions and causing unwanted\nside effects. Prof Leung\u2019s team has made a breakthrough with their \u2018protein\ndetective\u2019 technology. By using iridium probes, they are able to tag the Keap1\nprotein, making it impossible for the protein to hide. Then, with\nhigh-throughput screening, they can quickly identify active compounds capable\nof effectively separating Keap1 from Nrf2, allowing the \u2018fire brigade\u2019 to get\nback to work.<\/p>\n\n
Through systematic screening, the team has also discovered that an\nextract from a Chinese herbal medicine can precisely dismantle the Keap1-Nrf2\nprotein complex. This extract not only shows impressive anti-inflammatory\neffects, but is also safe, gentle, and non-irritating. Based on current cost\nevaluations, products made with this extract could be widely available at an\naffordable price.<\/p>\n\n
\u2018Rather than brutally suppressing symptoms, our technology provides a\nprotective shield for the skin and helps it learn to self-regulate,\u2019 Prof Leung\nexplains vividly. The team is preparing to apply for a patent for their\ntechnology and has drawn interest from cosmetics companies, with the first\nanti-inflammatory skincare product expected to launch in the near future.<\/p>\n\n
Putting Out the \u2018Slow-Burning Fire\u2019 of\nChronic Inflammation<\/p>\n\n
Chronic inflammation, like a slow-burning fire, can quietly harm the body\nand last for months or even years. For example, office workers often suffer\nfrom chronic muscle strain caused by sitting for long periods and poor posture,\nwhich leads to stiff necks and shoulders. Middle-aged and elderly people\ncommonly experience osteoarthritis or arthritis, while sports enthusiasts may\ndevelop chronic tendinitis from ligament and tendon injuries caused by\novertraining or insufficient recovery.<\/p>\n\n
To address these issues, Prof He Chengwei, associate professor in ICMS,\nworking with his team, systematically screened dozens of medicinal plants. They discovered that Glycine tabacina<\/i> (\u7159\u8c46), a plant commonly found in Fujian and Taiwan, possesses remarkable\nanti-inflammatory potential. In traditional Chinese medicine, Glycine tabacina<\/i> is used to relieve\ndampness, support the spleen and kidneys, and strengthen muscles and bones.\nHowever, its anti-inflammatory efficacy and mechanisms have not been fully\nexplored. Through modern pharmacological research, Prof He\u2019s team revealed for\nthe first time that coumestrol and isoflavonoids in Glycine tabacina <\/i>can precisely regulate multiple inflammatory signalling\npathways, including SYK, TAK1, PI3K, and NF-\u03baB. Functioning like a \u2018precision\nfirefighting system\u2019, these compounds not only reduce chronic inflammation but\nalso promote bone repair and improve osteoporosis.<\/p>\n\n
Building on this discovery, the team combined traditional wisdom with\nmodern technology to develop \u2018Macao One Root\u2019\u2014a topical adhesive that can relax\nmuscles, improve circulation, and effectively alleviate chronic inflammatory\npain. This innovative product has already secured four invention patents, and\nthe team is collaborating with medical product companies to scale up\nproduction. Prof He explains that the Chinese nickname for Glycine tabacina<\/i>, \u2018One Root\u2019 (\u4e00\u689d\u6839), comes from a folk tale about a legendary herbal remedy in the\nMing-Qing Dynasty. According to the tale, residents of the Kinmen Islands\nbrewed tea or wine from Glycine tabacina<\/i>\nroots to ease the rheumatic pain of soldiers struggling to adapt to the\nislands\u2019 climate. \u2018With modern technology, we are able to validate this\nancestral knowledge. The \u201cMacao One Root\u201d patches honour history while\ndemonstrating the dedication of Macao researchers,\u2019 says Prof He.<\/p>\n\n
Groundbreaking Smart Anti-Inflammatory\nBiomaterial<\/p>\n\n
In medicine, the balance of macrophages functions like a precise\nregulator of health. M1 macrophages act as the body\u2019s \u2018defence forces\u2019,\nresponsible for attacking pathogens. However, if overactivated, they can cause\nchronic inflammation and disrupt the wound-healing process. On the other hand,\nM2 macrophages function as the body\u2019s \u2018repair engineers\u2019, promoting tissue\nregeneration. Yet, an excessive presence of M2 macrophages may promote tumour\nrecurrence or suppress hair follicle regeneration.<\/p>\n\n
To address these challenges, Prof Qu Songnan, professor in the Institute\nof Applied Physics and Materials Engineering, and his team conducted in-depth\nanalysis and identified three key limitations in current therapies. First,\nalthough natural biomaterials like hydrogels can modulate immune responses\nbetween M1 and M2 macrophages, the rigid crosslinked structure of hydrogels\ncannot adapt to the dynamic microenvironment needed for tissue repair. Second,\nin tumour immunotherapy, tumour-associated macrophages (TAMs) form an\nimmunosuppressive barrier that significantly reduces the effectiveness of\ntreatments. Finally, and most critically, existing treatments for chronic\nwounds lack precise methods to regulate the immune microenvironment. These\nfindings prompted the team to raise an ambitious question: Could an intelligent\nmaterial be developed to actively \u2018communicate\u2019 with the immune system and\ntackle these challenges at their root?<\/p>\n\n
After years of research, the team achieved a major breakthrough. By\ncombining natural egg white protein with carbon nanodots, they created an\ninnovative biomaterial called the \u2018carbon-dot-linked egg white hydrogel\u2019. This\nmaterial features three transformative capabilities. First, it has an adaptive\ndynamic crosslinking structure that responds to the changing needs of tissue regeneration\nat different stages. Second, it incorporates a chronologically programmed drug\ndelivery system that aligns precisely with therapeutic windows. Finally, and\nmost critically, it can directly reprogramme the immune microenvironment by\nprecisely modulating macrophage phenotypes (M1\/M2 polarisation). This\nbreakthrough marks a paradigm shift in biomaterials, evolving them from passive\nstructural carriers into active systems that can modulate immune responses.<\/p>\n\n
When applied to tumour resection sites, the carbon nanodots within the\nhydrogel function as a sophisticated precision guidance system. They\neffectively repolarise tumour-associated macrophages, shifting them from\npro-tumour M2 phenotypes to tumour-suppressing M1 phenotypes. At the same time,\nthey activate T cell-mediated immunity\nby disrupting PD-L1 expression on cancer cells. This innovative therapy has\ndemonstrated remarkable efficacy in animal trials, significantly reducing\ntumour recurrence rates and presenting a groundbreaking postoperative treatment\nstrategy.<\/p>\n\n
The smart hydrogel also offers a revolutionary solution for chronic\nwounds. By releasing stage-specific regenerative signalling molecules, it\ntransforms overactive M1 macrophages into pro-healing M2 phenotypes,\nsignificantly reducing the risk of amputations in diabetic patients. Equally\nimpressive is its efficacy in hair follicle regeneration. The hydrogel\u2019s\ndegradation rate naturally synchronises with the hair growth cycle, while its\nprecise immunomodulation activates dormant follicular stem cells, providing new\nhope for patients suffering from alopecia.<\/p>\n\n
Prof Qu and his team\u2019s groundbreaking research has been published in leading international journals, including Advanced Science <\/i>and Advanced Materials<\/i>, and has been granted invention patents in\nmainland China. The project is now incubated at the UM Centre for Innovation\nand Entrepreneurship, with clinical trials expected to begin in two years.\nEmphasising the broader impact of their work, Prof Qu says, \u2018This is not just a\nnew material. It also serves as a versatile therapeutic platform with the\npotential to transform treatments for immune-related diseases.\u2019<\/p>\n\n
UM\u2019s\nAnti-Inflammatory Philosophy <\/p>\n\n
From persistent skin rashes and chronic joint pain to cancer\nrecurrence, many seemingly unrelated health issues stem from a common root\ncause: immune system dysregulation. Instead of relying on\nconventional immunosuppressive approaches, UM\u2019s \u2018fire brigade\u2019 is pioneering\ninnovative methods to reboot the immune system and restore the body\u2019s natural balance.\nWe look forward to seeing these groundbreaking studies move from the laboratory\nto clinical applications and, ultimately, to the market. This will offer hope\nto countless individuals in overcoming the challenges of inflammation and\nreclaiming their health and well-being.<\/p>
<\/p>
Text: Kelvin U<\/p>
Photo: Provided by the interviewees<\/p>
English Translation: Kelvin U, Bess Che<\/p>