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Tag: Hong Kong Baptist University

HKBU develops multifunctional nanoparticle for diagnosis and treatment of glioma

Posted on by HKBUCPRO

A Hong Kong Baptist University (HKBU) collaborative research team has synthesised a nanoparticle named TRZD that can perform the dual function of diagnosing and treating glioma in the brain. It emits persistent luminescence for the diagnostic imaging of glioma tissues in vivo and inhibits the growth of tumour cells by aiding the targeted delivery of chemotherapy drugs. The nanoparticle offers hope for the early diagnosis and treatment of glioma, especially cerebellar glioma, which is even harder to detect and cure with existing methods.

The research results have been published in Science Advances, an international scientific journal.

Limitations of existing diagnostic and therapeutic approaches

Glioma is the most common form of malignant primary brain tumour, and it accounts for about one-third of all brain tumours. Magnetic resonance imaging (MRI) is commonly used to diagnose glioma, but the technology is not that sensitive. Cerebellar glioma, a relatively rare brain tumour, is even harder to detect with MRI. To facilitate early detection and treatment, an alternative method with improved sensitivity and precision is needed to diagnose glioma.

Doxorubicin, a chemotherapy agent, is an effective treatment for glioma. However, its application may also damage normal cells, and it is associated with a range of side effects. To enhance doxorubicin’s clinical efficacy and minimise its side effects, a novel approach is needed to apply the drug to tumour cells in a more targeted manner.

In response to the diagnostic and therapeutic needs of glioma, a research team co-led by Dr Wang Yi, Assistant Professor of the Department of Chemistry at HKBU, and Professor Law Ga-lai, Professor of the Department of Applied Biology and Chemical Technology at the Hong Kong Polytechnic University, has synthesised a novel near-infrared (NIR) persistent luminescence nanoparticle called TRZD, which can play a dual role in diagnostic imaging and as a drug carrier for glioma.

TRZD has the characteristic of emitting NIR persistent luminescence after excitation with ultraviolet (UV) light. The basic structure of TRZD is a combination of nanoparticles, loaded with the mesoporous structure of silica, which makes it a good carrier of doxorubicin particles. Its surface is coated with red blood cell membranes to increase its stability, and it is embedded with T7 peptides. T7 peptides have a strong affinity for transferrin receptors which are abundant on the surface of tumour cells, and they can facilitate TRZD’s penetration through the blood-brain barrier.

An imaging probe for glioma diagnosis

The research team evaluated the efficacy of TRZ (i.e. TRZD without doxorubicin) in diagnostic imaging for glioma with a mouse model. TRZ particles were first excited by UV light to initiate luminescence. Mice with tumour tissues injected into their cerebrum and cerebellum were then treated with TRZ. In the following 24 hours, TRZ luminescence was detected at the tumour sites of the mice.

However, when the same experiment was conducted with TRZ without T7 peptides, and TRZ without both the red blood cell membrane coating and T7 peptides, no luminescence was detected at the tumour sites of the mice. The results show that the red blood cell membrane coating can prolong the function of TRZ by stabilising the nanoparticle, and it can slow down its natural uptake by the human body. On the other hand, T7 peptides are instrumental in TRZ’s penetration into and accumulation in tumour cells, so that it can perform its imaging function for glioma.

Dr Wang said: “Our experiment suggests that TRZ is a promising bioimaging agent for the diagnosis of glioma. It was observed that TRZ’s luminescence can be detected in tumour cells in both the cerebrum and cerebellum regions of the brain, which is an encouraging result because glioma in the cerebellum region is difficult to detect with existing diagnostic methods. As a result, TRZ offers new hope for the timely and accurate diagnosis of glioma.” 

TRZD inhibits the growth of glioma and extends the lifespan of mice

The research team further evaluated the anti-tumour efficacy of TRZD using a group of mice who had had their cerebrum and cerebellum injected with tumour tissues. After applying TRZD for 15 days, the average diameter of their tumours was reduced to 1 mm. They also survived 20 days longer on average compared to the control group, who had not received TRZD. Besides, cell death was observed in the tumour region but not in normal brain tissue.

Dr Wang said: “The experimental results indicate that TRZD’s therapeutic effect on glioma has good selectivity, because doxorubicin is brought specifically to tumour cells due to T7 peptide’s strong affinity with tumour cells’ surface receptors and its ability to penetrate the blood-brain barrier. As a result, doxorubicin can be applied in a more targeted manner, and hopefully its side effects can be minimised with a reduced drug dosage.

“We concluded that TRZD demonstrates promising potential, and it could be developed into a new generation of anti-glioma drugs that can perform the dual function of diagnosis and treatment. It also offers hope for the development of treatment protocols for other brain diseases.”

HKBU scientists develop versatile compound for treating Alzheimer’s disease

Posted on by HKBUCPRO

A study led by researchers from Hong Kong Baptist University (HKBU) has demonstrated that a multifunctional organic compound named F-SLOH has the potential to treat Alzheimer’s disease (AD) at an early stage. The team found that it can inhibit the aggregation of amyloid-beta (Aβ), and reduce the hyperphosphorylation of tau proteins and neuroinflammation in the brain to improve the pathological features of AD. The findings have been published in the international academic journal Redox Biology.

AD is the most common cause of dementia. It accounts for nearly 65% of dementia cases in elderly Hong Kong Chinese. It is pathologically characterised by the abnormal aggregation of Aβ, the hyperphosphorylation of tau proteins and neuroinflammation in the nerve cells in the brain, which cause progressive neuronal loss and cognitive impairment. Currently there is no cure for AD, and the available medicines can only relieve its symptoms. Inhibiting the abnormal aggregation of Aβ and the hyperphosphorylation of tau proteins is considered the primary and a promising therapeutic approach to treat AD.

F-SLOH as theragnostic agent for AD

In the search for novel therapeutic and diagnostic methods for AD, a research team comprising Professor Li Min, Professor of the Teaching and Research Division and Associate Dean of the School of Chinese Medicine; Professor Ricky Wong Man-shing, Professor of the Department of Chemistry of the Faculty of Science; and Dr Iyaswamy Ashok, Research Assistant Professor of the Teaching and Research Division of the School of Chinese Medicine at HKBU, demonstrated the in vivo therapeutic efficacy of a compound called F-SLOH in reducing the abnormal aggregation of Aβ, the hyperphosphorylation of tau proteins and neuroinflammation in the nerves cells in the brain, thereby improving the learning and memory functions of mice with AD.

F-SLOH is a multi-functional cyanine probe synthesised by a team led by Professor Ricky Wong Man-shing for the detection of biological materials such as proteins and peptides. Its features include real-time visualisation of Aβ aggregation in brains, excellent permeability across the blood-brain barrier and low bio-toxicity. Previous studies showed that F-SLOH could inhibit the abnormal aggregation of Aβ species and provide neuroprotection against neurotoxicity induced by the abnormal aggregation of Aβ in vitro at the cellular level.

F-SLOH improves pathological features in AD mice

To determine the therapeutic efficacy of F-SLOH for AD, the researchers injected or fed F-SLOH to a group of transgenic AD mice. Histopathology and biochemical analyses showed that in mice treated with F-SLOH, Aβ oligomers (one of the Aβ species) and Aβ plaque deposits (the clumps of Aβ) were dramatically reduced in their hippocampus and their brains when compared with the AD mice in the control group who had not been fed F-SLOH.

The researchers also found that F-SLOH can reduce the levels of an amyloid precursor protein that generates Aβ and tau protein hyperphosphorylation. In an immunoblot analysis of the transgenic AD mice brian, the F-SLOH treatment group showed a significant reduction in the levels of the amyloid precursor protein and its metabolites compared to the control group.

In other experiments on the transgenic AD mice after F-SLOH treatment, the researchers separated the soluble and insoluble tau proteins in their brain tissue samples. The results showed that F-SLOH treatment significantly reduced the levels of insoluble tau protein in the brains of AD mice, which forms neurofibrillary tangles, one of the pathological features of AD.

F-SLOH improves memory and cognitive functions in AD mice

Aggregation of Aβ is closely related to the dysfunction of the links between nerve cells and memory decline. The researchers conducted two experiments to test the memory functions of AD mice. In the first experiment, mice were trained to swim in a water maze, reach a platform and remember its position. After the platform was removed, researchers observed whether the mice were able to recall and approach the original position of the platform. Compared to the control group, transgenic AD mice treated with F-SLOH spent more time swimming around the platform’s original position, showing that they can better memorise the platform’s location.

In the second experiment, mice were placed in a chamber and exposed to an audio tone followed by an instant small electric shock to their feet from the floor of the chamber. On the following day, they were put back in the chamber but without any electric shock. When the mice were exposed to the same audio tone, they “froze” their body movements due to the fear of an electric shock. The transgenic AD mice treated with F-SLOH exhibited a longer freezing time than that of the control group.

The results of the two experiments showed that AD mice treated with F-SLOH have better memories compared to the control group, suggesting that F-SLOH improved AD mice’s memory and cognitive functions.

F-SLOH shows early potential for treating AD

The researchers also revealed that F-SLOH degraded the abnormal aggregation of Aβ and reduced the levels of tau protein hyperphosphorylation, the amyloid precursor protein and its metabolites through the activation of the transcription factor EB. Transcription factor EB is the main regulator of the autophagy-lysosomal pathway, a major mechanism for degrading ageing intracellular macromolecular proteins, including the intracellular metabolites such as Aβ aggregates.

Professor Li Min said: “AD patients lose their self-management abilities and require long-term care as the disease progresses. As the population is ageing in Hong Kong, the prevalence of AD is likely to increase. There is an urgent need to develop new drugs that can treat or slow down the progression of AD. The current study suggests that the compound F-SLOH has promising theragnostic potential for treating AD at an early stage.”

Professor Ricky Wong Man-shing said: “The study provides the first in vivo evidence that F-SLOH is an effective agent that can target and treat multiple neurodegenerative changes in an AD mouse model. The research findings can drive advancements in AD diagnosis and treatment in humans.”

HKBU at forefront of human-AI symbiotic art creation with innovative performance

Posted on by HKBUCPRO

A pioneering and bold attempt to apply artificial intelligence (AI) technologies in the performing arts was carried out by Hong Kong Baptist University (HKBU) in a public concert held on 14 July in Hong Kong.

The innovative performance was the first human-AI collaboration of its kind in the world, and it showcased how AI can be a creative force that can perform music, create cross-media art, and dance.

The performance was powered by the AI technologies developed by HKBU scientists under the “Building Platform Technologies for Symbiotic Creativity in Hong Kong” research project. The concert, dubbed “A Lovers’ Reunion”, was the Annual Gala Concert of the HKBU Symphony Orchestra, and it was conducted by its music director, Professor Johnny M Poon.

The research project is led by Professor Guo Yike, Vice-President (Research and Development) of HKBU, and supported by HK$52.84 million (US$6.77 million) in funding from the Theme-based Research Scheme under the Research Grants Council. Its deputy project coordinator, Professor Johnny M Poon, is the Associate Vice-President (Interdisciplinary Research) and the Founding Dean of HKBU’s School of Creative Arts.

The project team also comprises computer scientists from HKBU’s Augmented Creativity Lab. The unique mix of scientists and artists in the project team enables them to merge their cross-disciplinary knowledge and come up with sparkling ideas on how to unleash the endless possibilities of art creation with the infusion of cutting-edge technologies.

At the Concert, the project team presented a performance that marked the first time in the world that an AI choir had combined with an AI-generated visual storyteller to perform interactively with a conductor and an orchestra. The HKBU Symphony Orchestra shared the stage with an AI virtual choir to perform a newly arranged version of the song Pearl of the Orient with the voices of 320 virtual performers.

The AI virtual choir was “trained” by HKBU researchers using the generative models of singing that they built by extracting and disentangling key contributing features of vocal singing from a collection of songs recorded by professional singers.

An AI media artist learnt from the lyrics of the Pearl of the Orient, and it created a stunning cross-media visual narrative of the song according to its interpretation of the underlying meaning of the lyrics. Unlike the conventional AI machines that import images as a reference for the algorithms to mimic, it used textual lyrics as the sole input so that it can associate the underlying meaning of the lyrics with an appreciation of the beauty of Hong Kong.

Another highlight of the Concert was a ballet performance featuring AI virtual dancers in Ravel’s Daphnis et Chloé, accompanied live by the HKBU Symphony Orchestra. With the help of professional dancers from the Hong Kong Dance Company, the AI virtual dancers interpreted the underlying emotional and aesthetic connections between the music and the dance. The dance movements, inspired by a newly discovered species of box jellyfish in Hong Kong, were then choreographed.

Please click here to view highlights of the performance, and click here for more production details of the performance.

The AI-driven performance is one of the many milestone deliverables of the “Building Platform Technologies for Symbiotic Creativity in Hong Kong” research project, and others include an art data repository, a generative AI algorithms system, a research theatre, a digital art and policy network, and some unique and creative application projects, to name but a few.

Another important initiative HKBU is organising is the “Human, Machine, Art, Creativity: International Symposium” in the Hong Kong Convention and Exhibition Centre on 9 August.

“AI is revolutionising numerous fields of knowledge, and it is playing a more and more significant role in many creative processes like music, visual arts and architecture. The Symposium will gather world-renowned researchers from academia and industry, crossing different expertise areas, to jointly discuss emerging topics in human-AI symbiotic art creativity,” said Professor Guo.

The Symposium will cover topics including the enabling technologies of symbiotic art creation and manifestation, the aesthetics and cognitive values of symbiotic art creativity, the new trend of the art economy with Web 3.0, new issues raised by the new forms of art in society, and the impact on art community stakeholders, among others.

Interested parties can visit the Symposium’s website for more details.

HKBU launches the ground-breaking Turing AI Orchestra

Posted on by Editorial Team

On 9 August, Hong Kong Baptist University (HKBU) announced the launch of the ground-breaking “Turing AI Orchestra” (TAIO) — the next milestone in its visionary plan to explore and broaden the scope of possibilities in art co-creation by humans and artificial intelligence (AI). TAIO is the world’s first virtual ensemble built with state-of-the-art AI technology, signifying a new form of collaboration between humans and machines.

The announcement was made during the “Human, Machine, Art, Creativity: International Symposium” co-organised by HKBU and the Hong Kong Productivity Council, where world-renowned artists, researchers, scholars and industry professionals gathered to discuss the development of human-AI symbiotic art creativity.

Both the Symposium and TAIO are deliverables under a research project co-led by Professor Yike GUO, Vice-President (Research and Development), and Professor Johnny POON, Associate Vice-President (Interdisciplinary Research), of HKBU. The five-year project, titled “Building Platform Technologies for Symbiotic Creativity in Hong Kong”, had been granted a significant funding of HK$52.8 million by Hong Kong’s Research Grants Council for developing platform technologies in support of symbiotic creativity.

TAIO aims to provide an open platform for artists and scientists from around the world to collaborate in a dynamic and innovative environment, and will play a useful role in AI research and development that will disrupt the world of art. It also echoes one of the research project’s tasks — to build a Digital Art and Policy Network for symbiotic creativity collaboration and related policy innovation. With the help of Blockchain technologies, TAIO will also help realise the world’s first Decentralised Autonomous Organisation (DAO) ecosystem for art creation.

Another key project deliverable closely related to TAIO was a human-AI joint performance during the annual gala concert of the HKBU Symphony Orchestra in July titled “A Lovers’ Reunion.” The performance, featuring an AI choir with the voices of 320 virtual singers, together with an AI media artist who could interpret lyrics, and a group of AI dancers, was the first of its kind in the world. It was powered by the AI technologies developed by the scientists from HKBU’s Augmented Creativity Lab under Professor Guo’s headship.

TAIO symbolises how HKBU is pushing the frontiers of art-tech to transform the development of art and culture. It is hoped that TAIO will help drive the advancement of art-tech in Hong Kong, and thereby enabling the city to become a global leader in the field as well as an international cultural and art hub. In the time to come, TAIO will undoubtedly revolutionise creative art processes and performances, opening a new era of art-tech for the benefit of the world.

HKBU establishes the School of Creative Arts

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To further augment human creativity in the world of arts, Hong Kong Baptist University (HKBU) will establish the School of Creative Arts with effect from 1 July with a revitalised vision to nurture the next generation of creative talent for Hong Kong, and contribute to the city’s development as a creative arts hub for China and the world.

Professor Alexander Wai, President and Vice-Chancellor of HKBU, said: “Recent advancements in digital technology have opened up new avenues in the world of arts. On top of this, the Government’s Policy Address in 2021 expressed its vision to position Hong Kong as Asia’s city of culture and creativity. The National 14th Five-Year Plan also raised the level of support for Hong Kong to help it develop into a hub for arts and cultural exchanges between China and the rest of the world.

“By capitalising on the new opportunities and the latest technological advancements, and with the synergies created by the establishment of the School of Creative Arts, the University will take the development of the creative arts to a higher level, and set new standards for future teaching and research.”

The School of Creative Arts will be comprised of three constituent academic units, namely the Academy of Film, Academy of Music and Academy of Visual Arts. By integrating related talent and resources of the University, it will be a place where great minds in the creative arts and technology can meet, and it will provide HKBU with a strong platform to advance the arts and culture, as well as art-tech, in Hong Kong and the region.

Professor Johnny ML Poon, Associate Vice-President (Interdisciplinary Research) and Dr Hung Hin Shiu Endowed Professor in Music at HKBU, has been appointed as the School’s Founding Dean.

“The School of Creative Arts is well poised to disrupt creative practice and art education in film, music and visual arts. Certain aspects of the world of arts – namely, its creative genealogy and methodology – require a radical rethink. A new framework of education and research is needed for artists to ‘think’ about futurity.

“Inspired by Abraham Lincoln’s famous quote ‘the best way to predict your future is to create it’, the new school, rooted in HKBU’s liberal arts ethos and transdisciplinary inquiries, aims to interrogate the infinite acts of human creativity, reassess the different roles of the arts in our time, and create new artistic opportunities for the future,” said Professor Poon.

The School of Creative Arts attaches great importance to transdisciplinary teaching and learning to nurture future-ready talent for Hong Kong and the nation who can innovate solutions and tackle the challenges of the times through ideation that transcends the boundaries of disciplines. On top of the existing programmes offered by the University in the disciplines of acting, film, music and visual arts, two new transdisciplinary programmes, namely the Bachelor of Arts and Science (Hons) in Arts and Technology and the Bachelor of Arts (Hons) in Business Administration (Global Entertainment), will be launched by the University in the 2022/23 academic year, and they will be housed in the School.

In terms of research and professional development, the integrated talent pool of the School of Creative Arts, which comprises experts from different arts disciplines, can facilitate broader collaboration with local and overseas universities, research institutions, government departments, professional bodies and industries.

Furthermore, the School’s capacity to fuel the development of the creative arts will be substantially strengthened with the expected completion of the Jockey Club Campus of Creativity in 2024, which will feature state-of-the-art facilities for a comprehensive range of creative arts disciplines.

With the School’s strengthened focus on the development of the creative arts for the future and the synergies created by the strategic realignment of its resources, it is expected that the University’s knowledge output in the creative arts and its impact can be maximised, enabling HKBU to become the research and education hub for the creative arts, culture and related industries in Hong Kong for China and the world.

HKBU biologists discover three new coral species in Hong Kong waters

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Biologists from Hong Kong Baptist University (HKBU) have discovered in Hong Kong waters three new species of hard coral which have never been identified anywhere else in the world. The findings come shortly after their discovery of one new coral and two new nudibranch species, which was announced last year under their research project on coral health in Hong Kong.

The new marine species were identified by Professor Qiu Jianwen and MPhil student Mr Yiu King-fung of HKBU’s Department of Biology. The descriptions of the new corals have been accepted for publication in the academic journal Zoological Studies.

New species found during coral health research

About eight years ago, Professor Qiu and his team started a series of research projects related to coral health in Hong Kong, including studies on the impact of coral bioeroding sea urchins and coral-eating nudibranchs, as well as coral bleaching caused by global warming. A coral facility was set up at HKBU to culture corals and conduct controlled experiments to examine their physiological changes under different culture conditions. With continuous field surveys and in-depth research, the team has revealed the high diversity of sun corals in Hong Kong waters.

The three new sun coral species discovered this time were named by the HKBU team as Tubastraea dendroida, Tubastraea chloromura and Tubastraea violacea, and they all belong to the genus Tubastraea. The samples were collected when the team surveyed coral-eating nudibranchs at Sung Kong and Waglan Island in the eastern waters of Hong Kong. With the addition of three new members, the number of known species in the Tubastraea genus has increased from seven to ten.

The features of the three new sun coral species are as follows:

Tubastraea dendroida

Similar to most sun corals, Tubastraea dendroida has a typical bright orange colour, but its shape is rather unique. Instead of growing in clumps like most of its related species, this new species has a tree-like structure, with the main stem of its colony attenuating from the base to the tip. The HKBU team therefore named it “dendroida” to reflect its tree-shaped body.

Tubastraea violacea

Covered with a thin layer of pale purple tissue on the corallites (skeletal cups), Tubastraea violacea stands out from other related sun coral species as its polyp wall tissues and skeleton are violet in colour, and it has been named “violacea” accordingly. Nevertheless, its tentacles are yellow and the corallites have a thick wall. Based on comparisons with DNA sequences in public databases, the team found that this species may have colour variants elsewhere, such as a yellow colour variant in New Caledonia in the South Pacific.

Tubastraea chloromura

This coral has a delicate olive green skeletal wall and a circle of yellow tentacles surrounding its mouth. As a result, the species has been named “chloromura”, with “chloro” and “murus” meaning “green” and “wall”, respectively.

From coral gene sequences recorded in public databases, HKBU biologists envisage the potential distribution of Tubastraea dendroida and Tubastraea violacea in Japan and the Western Pacific Ocean. However, at this stage, Tubastraea chloromura is only known to inhabit Hong Kong waters.

All of these three coral species are non-reef-building corals. They do not host symbiotic algae that produce nutrients and energy via photosynthesis. Living in deeper waters at depths of between 10 and 30 metres, they gain energy and nutrients by capturing zooplankton from seawater using their tentacles.

New species discoveries suggest rich biodiversity

“Our discovery of three new species of Tubastraea enhances our knowledge of the diversity of this sun coral genus. Given that corals are one of the best-studied marine animals, our study reveals how little we know about marine diversity, and how many undescribed species are still awaiting our discovery,” said Professor Qiu.

Identification of the three new coral species comes less than a year after Professor Qiu and his team announced their last discovery in October 2021. While implementing a project supported by the Environment and Conservation Fund to assess the diversity and impact of coral-eating nudibranchs, the team discovered a new sun coral species in the genus Tubastraea and two new species of nudibranchs in the genus Phestilla in Hong Kong waters.

Looking back, the last time a new hard coral species was discovered and named in Hong Kong was about 20 years ago. “The discovery is very encouraging as it provides strong evidence of the high marine biodiversity in Hong Kong waters, and it helps fill in the knowledge gaps in biodiversity as advocated in the Government’s Biodiversity Strategy and Action Plan. It also inspires us to further explore the diversity of marine animals, study their functions and ecosystem services, and protect them from potential human disturbances,” Professor Qiu added.

HKBU-led research identifies new regulatory mechanism of satiety, therapeutic target for obesity

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A research team led by Hong Kong Baptist University (HKBU) has found that a proteolytic enzyme called membrane-type 1 matrix metalloproteinase (MT1-MMP) plays an important role in the regulatory mechanism of fullness, or satiety, and it could serve as a promising potential drug target for the management of obesity.

The research findings were published in the internationally-renowned scientific journal Nature Metabolism. The study has also been featured as a research highlight in multiple high-impact journals, including Nature Reviews Endocrinology, Nature Metabolism and Science Signaling.

Half of Hong Kong’s population obese or overweight

Being overweight, especially to the extent of obesity, exposes people to a higher risk of life-threatening diseases such as cardiovascular diseases, diabetes, and cancer. According to the Population Health Survey conducted in 2014/15 by the Department of Health, about 30% of people in Hong Kong aged 15 to 84 were obese, and another 20% were overweight.

The most effective way to tackle obesity is to reduce food consumption, but obese people often encounter difficulties in regulating their dietary habits as they lose their sense of satiety. Identifying a factor that specifically controls body weight, and investigating how it regulates our sense of satiety, is crucial for the development of therapeutic approaches for obesity.

Identification of new regulator of satiety signals

A research team led by Dr Xavier Wong Hoi-leong, Assistant Professor of the Teaching and Research Division of the School of Chinese Medicine (SCM), and Professor Bian Zhaoxiang, Director of the Clinical Division of SCM and Tsang Shiu Tim Endowed Chair of Chinese Medicine Clinical Studies at HKBU, identified a proteolytic enzyme called MT1-MMP which regulates the mechanism of issuing satiety signals in the human brain.

Growth and differentiation factor 15 (GDF15) is a hormone that sends out satiety signals by binding with the neuron receptor in the hindbrain called GDNF-family receptor α-like (GFRAL). Mediation of GFRAL can therefore affect the ability of GDF15 to send satiety signals, and thus help regulate food intake. From this starting point, the research team conducted a series of experiments to investigate the mediation effects of MT1-MMP on GFRAL.

Depletion of MT1-MMP reduces obesity

The research team generated an obesity mouse model by feeding a fat-rich diet to a group of transgenic mice with a depletion of MT1-MMP in their satiety neurons, as well as a control group of ordinary mice. After 16 weeks, the mice with depleted MT1-MMP ate 10% less food, gained 50% less weight, and exhibited reduced glucose and plasma insulin levels compared to the control group. The results show that depletion of MT1-MMP protects mice from obesity induced by a high-fat diet.

Following analysis with western blots, a widely used analytical technique that can detect specific proteins, the research team also found that the obese mice displayed an increased activity of MT1-MMP in the Area Postrema and Nucleus of the Solitary Tract, the brain regions involved in appetite and weight regulation. The finding suggests that increased MT1-MMP activity in the brain of obese mice could be a risk factor causing sustained weight gain.

To understand the mechanism by which MT1-MMP suppresses GDF15 satiety signalling, the research team conducted a series of molecular biology experiments involving animal models and cell culture. The results show that in cells with active MT1-MMP, a significant reduction of GFRAL and thus GDF15 signalling were observed. It could be explained by MT1-MMP clipping GFRAL from the surface of the brain neurons, which blocks GDF15 from binding to GFRAL and thus reduces the number of satiety signals. This in turn keeps the neurons from transmitting the satiety signals sent by GDF15.

MT1-MMP as a therapeutic target for obesity

The researchers also explored the therapeutic potential of targeting MT1-MMP for obesity management, in particular through pharmacological inhibition of its activity in vivo. With the application of a specific neutralising antibody that inhibits MT1-MMP, significant improvements in metabolic parameters including food intake, glucose tolerance and body weight in obese mice were observed. The results suggest that MT1-MMP is a potential therapeutic target that could be used in the development of innovative drug treatments for obesity.

Dr Wong said: “The research findings have established the role played by MT1-MMP in regulating satiety, and they have provided preliminary indications that the proteolytic enzyme is a promising target for the treatment of obesity. Pharmacological inhibition of MT1-MMP could be a viable strategy for the development of effective pharmacotherapy for the treatment of obesity.”

Apart from researchers from HKBU, the research team included scientists from The University of Hong Kong, The Chinese University of Hong Kong, the University of Texas Health Science Center at Houston, and the University of Helsinki.

HKBU joint research reveals gut microbial enzymes reactivate triclosan which induces colitis

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A Hong Kong Baptist University (HKBU) collaborative research study has revealed that certain gut microbial enzymes mediate the reactivation of triclosan (TCS) from its inactive glucuronide metabolite. TCS is an antimicrobial agent commonly used in a wide range of consumer products, and it is associated with the development of colitis.

The research results have been published in Nature Communications, an international scientific journal.

Mechanism of TCS exposure leading to colitis previously unclear

TCS is widely used as an antimicrobial agent in consumer products such as toothpaste, mouthwash, hand sanitisers, cosmetics and toys. It is a major environmental contaminant, and it has been shown that TCS exposure increases the risk of colitis.

Once TCS enters the human body, it is rapidly metabolised to form the biologically inactive metabolite TCS-glucuronide (TCS-G), which is easily eliminated from the body. Due to this characteristic, the mechanism of how environmental exposure to TCS leads to gut toxicity in the human body has previously remained unclear.

To answer this question, a research team co-led by Professor Cai Zongwei, Chair Professor of the Department of Chemistry and Director of the State Key Laboratory of Environmental and Biological Analysis at HKBU; Professor Matthew R Redinbo from the University of North Carolina at Chapel Hill; and Professor Zhang Guodong from the University of Massachusetts Amherst conducted a research study based on the hypothesis that certain gut microbial enzymes act on TCS-G in the gut, leading to the reactivation of TCS and the subsequent development of colitis.

TCS concentration uniquely high in the gut

To begin with, the research team sought to determine whether the gut has a different TCS metabolic profile compared to other body tissues. A group of mice were fed food that contained TCS. After four weeks, it was found that the biologically inactive TCS-G was dominant in their liver, bile, heart and small intestine, while the colitis-inducing TCS was dominant in the gut (cecum and colon). The results showed that the gut has a uniquely high concentration of TCS compared to other body tissues.

The research team then analysed the relationship between TCS-containing products and the concentration of TCS in the human body. In a group of human subjects who used TCS-containing personal care products for four months, both TCS and TCS-G were detected in their stool and urine samples, with TCS being dominant in stool and TCS-G being dominant in urine. However, TCS and TCS-G were not detected in the control group who used TCS-free personal care products. The results showed that the use of TCS-containing products leads to a high level of TCS, specifically in the human gut.

Gut microbiota significant in TCS-G conversion

The question remains why the human gut has a uniquely high TCS concentration. To answer this, the research team put forth the hypothesis that gut microbiota participate in the conversion of TCS-G to TCS, leading to the accumulation of TCS in the gut.

To test this hypothesis, the researchers observed that in an in vitro setting, cultured gut bacteria from both mice and humans were able to catalyse the conversion of TCS-G to TCS. To investigate whether the same phenomenon appears in an in vivo setting, the research team found that the inhibition of gut bacteria from mice by applying an antibiotic treatment almost reduced the concentration of TCS in their guts by half, and it increased the concentration of TCS-G by six-fold. The results affirmed that gut microbiota play a significant role in the conversion of TCS-G to TCS in the gut.

Specific enzymes catalyse TCS-G conversion

To investigate the mechanism by which gut microbiota catalyse TCS-G conversion, the research team focused on the intestinal β-glucuronidase (GUS) enzymes produced by gut bacteria in both mice and humans, because they have been shown to catalyse a wide range of metabolite conversions. Using a series of screening techniques, two types of GUS, namely “Loop 1” and “flavin mononucleotide (FMN)-binding” GUSs, were found to be most effective at converting TCS-G to TCS in vitro.

The research team then applied a GUS inhibitor, a drug that inhibits the function of Loop 1 and FMN-binding GUSs, to TCS-exposed and TCS-free mice. It was found that the GUS inhibitor could curb the conversion of TCS-G to TCS by the GUS enzymes. Colitis in TCS-exposed mice was also relieved after the application of the GUS inhibitor. The results support the notion that specific microbial GUS enzymes drive the conversion of TCS-G to TCS, and as a result, the chance of developing colitis is increased.

More stringent TCS controls needed

Professor Cai said: “Our research results clearly defined the mechanism by which gut microbiota are involved in the metabolism and toxicology of TCS, and the study offers a way to prevent the development of colitis following environmental exposure to chemicals.

“Regulatory bodies should consider imposing more stringent controls on the use of TCS. Although the US Food and Drug Administration (FDA) banned the marketing of TCS in over-the-counter antiseptic products in 2016, the chemical remains approved for use in a wide range of products. Transparency on TCS ingredients in product labelling and illustrations should also be improved so that consumers can be aware of the potential risks and make informed choices.”

HKBU fights against COVID-19 with Chinese medicine and comprehensive care

Posted on by HKBUCPRO

Given the recent upsurge in cases amid the COVID-19 pandemic in Hong Kong, Hong Kong Baptist University (HKBU) has established a transdisciplinary team of experts and supporting personnel to offer a free and integrated Chinese medicine prevention and treatment service, as well as emotional support resources to COVID patients, their close contacts and carers, with the aim of contributing to Hong Kong’s fight against the pandemic.

While HKBU offers free Chinese medicine prevention and treatment consultations and emotional support resources, a generous donation pledge of HK$10 million from the Tencent Charity Foundation has enabled HKBU’s School of Chinese Medicine (SCM) to provide and deliver free medicine to service users.

Transdisciplinary team offers medical and emotional support

The COVID-19 situation has got significantly worse since the beginning of the year, and Hong Kong’s public health system has been under huge pressure as a large number of patients have sought urgent medical treatment.

In a densely populated environment full of many vulnerable people at high risk of infection (such as those in elderly homes), managing the disease outbreak is particularly challenging. Apart from urgent support for disease prevention and treatment, patients – as well as their carers and close contacts – are facing huge emotional distress.

Professor Alexander Wai, President and Vice-Chancellor of HKBU, said: “HKBU is devoted to advancing the frontier of Chinese medicine research, and the efficacy of Chinese medicine for the prevention and treatment of COVID-19 has been proven clinically. In view of the pandemic’s development and in line with our caring spirit, the University has promptly assembled a Chinese medicine team to participate in the fight against the virus, with the hope of helping patients with urgent needs and alleviating the pressure on the public healthcare system. At the same time, our Department of Social Work is also offering an emotional support and counselling service in elderly homes to take care of the mental health of patients and staff. A number of university departments are also providing administrative support, with the aim of joining hands to tackle the COVID-19 challenge.”

Free consultations and medication

HKBU’s Chinese medicine team launched the “Free Online Consultation Service for COVID-19 Patients” in mid-February. It targets patients under quarantine in the community with no critical symptoms who do not require hospitalisation. Chinese medicine practitioners of HKBU will conduct consultations with patients through WhatsApp video-conferencing, prescribe medicine for them according to their clinical symptoms and body constitutions, and provide a medicine dispensing service. The consultation, medicine and delivery are free of charge.

Due to the overwhelming public demand for the service, the University has swiftly gathered together the resources needed to set up the HKBU Chinese Medicine Telemedicine Centre Against COVID-19 in two weeks’ time as an integrated hub to handle appointments, consultations and drug delivery matters. A designated online platform was also constructed to facilitate public registration for the service. The online consultation service has so far served more than 8,000 patients, close contacts and carers, and it can serve up to 1,000 patients every day. Under the scheme, Chinese medicine practitioners of the HKBU Chinese medicine clinics have offered consultations to the public. HKBU is recruiting its Chinese medicine alumni to join the medical team in response to the keen demand for the service.

Special scheme for elderly homes

Due to the serious nature of the outbreaks in elderly homes, HKBU is cooperating with the Hong Kong Association of Gerontology to launch a special scheme which offers remote consultations and medicine delivery to the residents and staff members of accredited elderly homes. So far 64 elderly homes have decided to join the scheme. HKBU has been providing the same service to 30 elderly homes so far referred by the Hospital Authority. The service has also been offered to staff members of St. James’ Settlement to help them maintain continuous services to around 5,200 home-based elders.

Furthermore, the elders and staff who are suffering from emotional distress due to the disease will be invited to join a mental health support service. The cases concerned will be referred to the Social Work Practice and Mental Health Centre of the Department of Social Work at HKBU. Volunteers who have been trained by the Centre will contact the cases by phone to provide emotional support or counselling. After the first over-the-phone mental health support session, volunteers will assess whether a second or even a third over-the-phone follow up counselling session is necessary. Launched in early March, the service will match the elders and staff in need with volunteers with phones.

Holistic service looks after physical and mental health

Professor Bian Zhaoxiang, Associate Vice-President (Chinese Medicine Development) and Director of the Clinical Division of SCM at HKBU, said that the participation of SCM in the treatment of COVID-19 will provide valuable experience and strengthen the role of Chinese medicine in Hong Kong’s healthcare system.

He said: “By combining our clinical treatment observations and the experience of the Chinese medicine sector, and with reference to the Mainland’s COVID-19 treatment protocol, SCM has compiled the “COVID-19 Chinese Medicine Diagnosis and Treatment Protocols for Hong Kong”. It covers the Chinese medicine approach to the prevention of COVID-19, as well as the treatment and rehabilitation of patients with mild to moderate cases of the disease. We hope that the compilation of this protocol can standardise HKBU’s clinical treatment for COVID-19, provide an operational reference for the Chinese medicine sector, and contribute to the adoption of Chinese medicine in terms of the prevention and treatment of emerging infectious diseases in the long run.”

Professor Daniel Lai, Dean of the Faculty of Social Sciences and Chair Professor of the Department of Social Work at HKBU, pointed out that some people may experience emotional distress in view of the prolonged COVID-19 pandemic. He said: “Under the gloomy atmosphere of the COVID-19 upsurge, patients worry about their illnesses, and their carers and close contacts also encounter emotional distress due to the pressure of taking care of the patients and the imminent infection risk they face. This situation is common in elderly homes where there are widespread disease outbreaks. We hope to provide emotional counselling to participants of HKBU’s Chinese medicine service who are in need, so that we can offer total care for their physical and mental health.”

Tencent Charity Foundation provides full support

The fifth wave of the COVID-19 pandemic has presented Hong Kong with a huge challenge and overloaded its healthcare system. Many infected patients are waiting for medical treatment, and they feel helpless as they remain stuck in the community. In response to Hong Kong people’s urgent needs, Tencent has donated HK$10 million through the Tencent Charity Foundation to HKBU. The donation will support the HKBU School of Chinese Medicine’s efforts in the fight against the pandemic through the establishment of the “HKBU Chinese Medicine Team Against COVID-19”. The team will be responsible for related prevention and treatment work, and they will offer an online Chinese medicine consultation service to the public with the hope of helping patients and close contacts in need.

Professor Wai said: “I would like to express my heartfelt gratitude to the Tencent Charity Foundation for taking the initiative to render support. The fifth wave of the pandemic is very challenging, and the Foundation has taken swift action to support the Chinese medicine team of HKBU with regard to the provision of timely assistance to the community, in particular offering our care to the elderly, while relieving the burden on the public healthcare system.”

The public can visit the following website for the appointment details as well as the consultation and medicine delivery arrangements of the Free Online Consultation Service for COVID-19 Patients:

https://cmc-booking.hkbu.edu.hk/

HKBU research reveals bisphenol S exposure may increase cancer risk

Posted on by HKBUCPRO

A study led by Hong Kong Baptist University (HKBU) has revealed that different degrees of exposure to bisphenol S (BPS), an industrial chemical widely used in paper products and plastic containers, are associated with the growth and deterioration of breast tumours in a mouse model. The research results suggest the need for more in-depth and comprehensive research on the potential negative impact of BPS on human health, and the ongoing search for a safer alternative for use in industrial production may be warranted.

Apart from the HKBU scientists, the research team also included researchers from the Shenzhen Institute of Advanced Technology at the Chinese Academy of Sciences and Xi’an Jiaotong University. The research results have been published in the Journal of Hazardous Materials, an international scientific journal.

Association between BPS and breast cancer under-researched
In the past, bisphenol A (BPA) was widely used in the production of a diverse range of products, such as baby bottles, food and beverage containers, and the thermal paper used for printing receipts. As previous research has shown an association between BPA exposure and human endocrine system disruption, metabolic disease and an increased risk of breast cancer in recent years, scientists have looked for alternatives to BPA, and BPS has been used as one of the substitutes. Despite reports on the adverse effects of BPS on human health, its impact on tumour progression and how it disrupts the relevant metabolic processes in breast cancer remain poorly understood.

A research team led by Professor Cai Zongwei, Chair Professor of the Department of Chemistry and Director of the State Key Laboratory of Environmental and Biological Analysis at HKBU, carried out several experiments to explore how BPS exposure at environmentally relevant levels affects the development of breast tumours, including the tumour’s morphological characteristics as well as lipid and protein distribution, with the aid of mass spectrometry imaging technology.

BPS exposure increases tumour volume and weight

The research team conducted experiments on three groups of mice model that had been transplanted with human breast cancer cells. In the first dosing group (BPS-10 group), the mice were fed daily with a lower dosage of 10 micrograms of BPS per kilogram of body weight for eight weeks. In the second group (BPS-100 group), the mice were fed with a higher dosage of 100 micrograms of BPS per kilogram of body weight. The mice in the control group were fed olive oil.

Tumour proliferation in the mice was then investigated, and the team used morphological analysis to study the breast tumour tissue. In general, increases in tumour volume and weight represent proliferation of tumour tissues. When a tumour further develops, the condition of its necrotic region and its peripheral tissues will change. However, the volume and weight of the tumour may reduce as a result of changes in the conditions of the tissues.

After the eight-week experiment, the average volume and weight of the tumours in the BPS-10 group were 13 times and 11 times higher than that of the control group respectively, and the average volume and weight of the tumours in the BPS-100 group were 4 times and 4.5 times higher than that of the control group respectively. Therefore, the results show that exposure to BPS was closely related to the proliferation and deterioration of breast tumours.

Different dosages associated with tumour proliferation and deterioration

The research team analysed the necrotic region and neoplastic region of the breast tumours in the three groups of mice. The two regions are common pathological features of solid tumours. An increase in the relative proportion of the necrotic region reflects the proliferation of the tumour, while an extended neoplastic region indicates the deterioration of the tumour.

 

In the control group, the status of tumour cells in the necrotic region and the neoplastic region was stable, and the mice from the group showed no significant tumour proliferation and deterioration after the experimental period. However, in the two BPS treated groups, an increase in tumour size was observed along with changes in the arrangement and distribution of tumour cells conducive to tumour proliferation and deterioration.

 

After the experiment, the necrotic regions in the BPS-10 and the BPS-100 groups accounted for 54.7% and 11.5% of the average section area of the tumours respectively. The results indicate that a low dosage of BPS induces faster tumour growth, and a high dosage of BPS may ultimately lead to deterioration of the tumour, as shown by the relatively small average size of the necrotic region and the extended neoplastic tissue in the BPS-100 group.

BPS affects the distribution of tumour-related lipids and proteins

The research team identified six lipid biomarkers that regulate tumour growth. With the analysis of tumour tissues’ morphological characteristics and the use of mass spectrometry imaging, it was found that in the two BPS-exposed groups, these lipids were highly abundant in the necrotic regions of breast tumours when compared with the control group. The team inferred that the metabolism of these tumour-regulating lipids was interrupted in the breast tumours following exposure to BPS.

The team also discovered the distribution of twelve protein biomarkers, including the proteins associated with breast tumour proliferation and deterioration. The results demonstrate the important function of BPS exposure-related lipids and proteins, and future research will further explore their role in breast cancer.

BPS may increase human breast cancer risk

The research team then compared the distribution of lipids and proteins in the BPS-exposed mice groups with those observed in human breast cancer tissue samples, and similar patterns were identified. While not all tumours will become cancerous, based on the benchmark results, the team deduced that exposure to BPS will increase the risk of breast cancer in humans.

“BPA was replaced by the less studied chemical BPS in industrial production. Our research findings show that BPS may potentially be associated with breast tumour proliferation, and further study is deemed necessary to unveil more about the chemical’s possible negative impact on human health. In the long run, industry may need to identify safer substitutes for both BPA and BPS. Policymakers should also establish relevant safety standards and regulations for the use of BPS,” said Professor Cai.