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Article ; Online: Plasma metabolomic profiling of patients with transient ischemic attack reveals positive role of neutrophils in ischemic tolerance.

Liu, Rongrong / Luo, Siwei / Zhang, Yu-Sheng / Tsang, Chi Kwan

2023 Volume 97, Page(s) 104845

Abstract: Background: Transient ischemic attack (TIA) induces ischemic tolerance that can reduce the subsequent ischemic damage and improve prognosis of patients with stroke. However, the underlying mechanisms remain elusive. Recent advances in plasma ... ...

Abstract	Background: Transient ischemic attack (TIA) induces ischemic tolerance that can reduce the subsequent ischemic damage and improve prognosis of patients with stroke. However, the underlying mechanisms remain elusive. Recent advances in plasma metabolomics analysis have made it a powerful tool to investigate human pathophysiological phenotypes and mechanisms of diseases. In this study, we aimed to identify the bioactive metabolites from the plasma of patients with TIA for determination of their prophylactic and therapeutic effects on protection against cerebral ischemic stroke, and the mechanism of TIA-induced ischemic tolerance against subsequent stroke. Methods: Metabolomic profiling using liquid chromatography-mass spectrometry was performed to identify the TIA-induced differential bioactive metabolites in the plasma samples of 20 patients at day 1 (time for basal metabolites) and day 7 (time for established chronic ischemic tolerance-associated metabolites) after onset of TIA. Mouse middle cerebral artery occlusion (MCAO)-induced stroke model was used to verify their prophylactic and therapeutic potentials. Transcriptomics changes in circulating neutrophils of patients with TIA were determined by RNA-sequencing. Multivariate statistics and integrative analysis of metabolomics and transcriptomics were performed to elucidate the potential mechanism of TIA-induced ischemic tolerance. Findings: Plasma metabolomics analysis identified five differentially upregulated metabolites associated with potentially TIA-induced ischemic tolerance, namely all-trans 13,14 dihydroretinol (atDR), 20-carboxyleukotriene B4, prostaglandin B2, cortisol and 9-KODE. They were associated with the metabolic pathways of retinol, arachidonic acid, and neuroactive ligand-receptor interaction. Prophylactic treatment of MCAO mice with these five metabolites significantly improved neurological functions. Additionally, post-stroke treatment with atDR or 9-KODE significantly reduced the cerebral infarct size and enhanced sensorimotor functions, demonstrating the therapeutic potential of these bioactive metabolites. Mechanistically, we found in patients with TIA that these metabolites were positively correlated with circulating neutrophil counts. Integrative analysis of plasma metabolomics and neutrophil transcriptomics further revealed that TIA-induced metabolites are significantly correlated with specific gene expression in circulating neutrophils which showed prominent enrichment in FoxO signaling pathway and upregulation of the anti-inflammatory cytokine IL-10. Finally, we demonstrated that the protective effect of atDR-pretreatment on MCAO mice was abolished when circulating neutrophils were depleted. Interpretation: TIA-induced potential ischemic tolerance is associated with upregulation of plasma bioactive metabolites which can protect against cerebral ischemic damage and improve neurological functions through a positive role of circulating neutrophils. Funding: National Natural Science Foundation of China (81974210), Science and Technology Planning Project of Guangdong Province, China (2020A0505100045), Natural Science Foundation of Guangdong Province (2019A1515010671), Science and Technology Program of Guangzhou, China (2023A03J0577), and Natural Science Foundation of Jiangxi, China（20224BAB216043).
MeSH term(s)	Humans ; Mice ; Animals ; Ischemic Attack, Transient/complications ; Ischemic Attack, Transient/metabolism ; Neutrophils/metabolism ; Stroke/complications ; Infarction, Middle Cerebral Artery/metabolism ; Metabolomics
Language	English
Publishing date	2023-10-25
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2023.104845
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Zs.A 7090: Show issues

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Article ; Online: The central role of natural killer cells in mediating acute myocarditis after mRNA COVID-19 vaccination.

Tsang, Hing Wai / Kwan, Mike Yat Wah / Chua, Gilbert T / Tsao, Sabrina Siu Ling / Wong, Joshua Sung Chih / Tung, Keith Tsz Suen / Chan, Godfrey Chi Fung / To, Kelvin Kai Wang / Wong, Ian Chi Kei / Leung, Wing Hang / Ip, Patrick

Med (New York, N.Y.)

2024 Volume 5, Issue 4, Page(s) 335–347.e3

Abstract: Background: Vaccine-related acute myocarditis is recognized as a rare and specific vaccine complication following mRNA-based COVID-19 vaccinations. The precise mechanisms remain unclear. We hypothesized that natural killer (NK) cells play a central role ...

Abstract	Background: Vaccine-related acute myocarditis is recognized as a rare and specific vaccine complication following mRNA-based COVID-19 vaccinations. The precise mechanisms remain unclear. We hypothesized that natural killer (NK) cells play a central role in its pathogenesis. Methods: Samples from 60 adolescents with vaccine-related myocarditis were analyzed, including pro-inflammatory cytokines, cardiac troponin T, genotyping, and immunophenotyping of the corresponding activation subsets of NK cells, monocytes, and T cells. Results were compared with samples from 10 vaccinated individuals without myocarditis and 10 healthy controls. Findings: Phenotypically, high levels of serum cytokines pivotal for NK cells, including interleukin-1β (IL-1β), interferon α2 (IFN-α2), IL-12, and IFN-γ, were observed in post-vaccination patients with myocarditis, who also had high percentage of CD57 Conclusion: Collectively, these data suggest that NK cell activation by mRNA COVID-19 vaccine contributed to the pathogenesis of acute myocarditis in genetically and epidemiologically vulnerable subjects. Funding: This work was funded by the Hong Kong Collaborative Research Fund (CRF) 2020/21 and the CRF Coronavirus and Novel Infectious Diseases Research Exercises (reference no. C7149-20G).
MeSH term(s)	Male ; Adolescent ; Humans ; Myocarditis/etiology ; Myocarditis/metabolism ; COVID-19 Vaccines/adverse effects ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Troponin T/metabolism ; Interferon-gamma/metabolism ; COVID-19/prevention & control ; Killer Cells, Natural/metabolism ; Cytokines/metabolism ; Vaccination/adverse effects ; Receptors, KIR2DL5/metabolism
Chemical Substances	COVID-19 Vaccines ; RNA, Messenger ; Troponin T ; Interferon-gamma (82115-62-6) ; Cytokines ; KIR2DL5B protein, human ; Receptors, KIR2DL5
Language	English
Publishing date	2024-03-22
Publishing country	United States
Document type	Journal Article
ISSN	2666-6340
ISSN (online)	2666-6340
DOI	10.1016/j.medj.2024.02.008
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Article ; Online: Sex differences in the associations of sleep-wake characteristics and rest-activity circadian rhythm with specific obesity types among Hong Kong community-dwelling older adults.

Lee, Priscilla Ming Yi / Liao, Gengze / Tsang, Chun Yuk Jason / Leung, Chi Chiu / Kwan, Mei-Po / Tse, Lap Ah

Archives of gerontology and geriatrics

2023 Volume 113, Page(s) 105042

Abstract: Background: Sex differences exist in sleep characteristics, circadian rhythm and body composition but the evidence on their associations with obesity risk remains unclear. We aimed to examine sex differences in the associations of sleep-wake cycle and ... ...

Abstract	Background: Sex differences exist in sleep characteristics, circadian rhythm and body composition but the evidence on their associations with obesity risk remains unclear. We aimed to examine sex differences in the associations of sleep-wake cycle and rest-activity circadian rhythm with specific obesity types among aged Chinese population. Methods: This report pooled data from 2 population-based surveys conducted during 4/2018-9/2018 and 7/2019-9/2020. All participants wore actigraphy on wrists for 7 days to measure their objective sleep patterns and rest-activity circadian rhythm. We measured participants' anthropometric data, and obtained their body weight, body fat percentage(fat%), visceral fat rating, muscle mass by calibrated bioelectrical impedance analysis device. Hand-grip strength was assessed by Jamar Hydraulic hand dynamometer. Multinomial logistic regression was performed to assess the odds ratio(OR) and 95% confidence intervals(95%CI). Results: We recruited 206 male and 134 female older adults with complete actigraphy data, with obesity prevalence of 36.9% and 31.3%, respectively. Male participants who had delayed sleep-wake cycle(i.e.,sleep-onset-time and wake-up time) was associated with higher risk of obesity(late sleep-onset-time:OR=5.28, 95%CI=2.00-13.94), and the results remained consistent for different types of obesity. Males with late M10(i.e., most active 10-hours) onset had higher adipose outcomes with an adjusted OR of 2.92(fat%:95%CI=1.10-7.71; visceral fat:95%CI=1.12-7.61). Among female participants, those with lower relative amplitude were associated with higher BMI and lower hand-grip strength. Conclusions: This study revealed that circadian rhythm fragmentation was associated with obesity and muscle loss. Promoting good sleep quality and maintaining robust circadian rhythm and physical activity can prevent poor muscle strength among older adults.
MeSH term(s)	Sex Factors ; Humans ; Male ; Female ; East Asian People ; Hong Kong ; Sleep ; Circadian Rhythm ; Obesity/classification ; Obesity/epidemiology ; Body Mass Index ; Hand Strength ; Prospective Studies ; Cross-Sectional Studies ; Aged ; Aged, 80 and over
Language	English
Publishing date	2023-04-25
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603162-6
ISSN	1872-6976 ; 0167-4943
ISSN (online)	1872-6976
ISSN	0167-4943
DOI	10.1016/j.archger.2023.105042
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Zs.A 1729: Show issues

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Article: Brain delivering RNA-based therapeutic strategies by targeting mTOR pathway for axon regeneration after central nervous system injury.

Li, Ming-Xi / Weng, Jing-Wen / Ho, Eric S / Chow, Shing Fung / Tsang, Chi Kwan

Neural regeneration research

2022 Volume 17, Issue 10, Page(s) 2157–2165

Abstract: Injuries to the central nervous system (CNS) such as stroke, brain, and spinal cord trauma often result in permanent disabilities because adult CNS neurons only exhibit limited axon regeneration. The brain has a surprising intrinsic capability of ... ...

Abstract	Injuries to the central nervous system (CNS) such as stroke, brain, and spinal cord trauma often result in permanent disabilities because adult CNS neurons only exhibit limited axon regeneration. The brain has a surprising intrinsic capability of recovering itself after injury. However, the hostile extrinsic microenvironment significantly hinders axon regeneration. Recent advances have indicated that the inactivation of intrinsic regenerative pathways plays a pivotal role in the failure of most adult CNS neuronal regeneration. Particularly, substantial evidence has convincingly demonstrated that the mechanistic target of rapamycin (mTOR) signaling is one of the most crucial intrinsic regenerative pathways that drive axonal regeneration and sprouting in various CNS injuries. In this review, we will discuss the recent findings and highlight the critical roles of mTOR pathway in axon regeneration in different types of CNS injury. Importantly, we will demonstrate that the reactivation of this regenerative pathway can be achieved by blocking the key mTOR signaling components such as phosphatase and tensin homolog (PTEN). Given that multiple mTOR signaling components are endogenous inhibitory factors of this pathway, we will discuss the promising potential of RNA-based therapeutics which are particularly suitable for this purpose, and the fact that they have attracted substantial attention recently after the success of coronavirus disease 2019 vaccination. To specifically tackle the blood-brain barrier issue, we will review the current technology to deliver these RNA therapeutics into the brain with a focus on nanoparticle technology. We will propose the clinical application of these RNA-mediated therapies in combination with the brain-targeted drug delivery approach against mTOR signaling components as an effective and feasible therapeutic strategy aiming to enhance axonal regeneration for functional recovery after CNS injury.
Language	English
Publishing date	2022-03-10
Publishing country	India
Document type	Journal Article ; Review
ZDB-ID	2388460-5
ISSN	1876-7958 ; 1673-5374
ISSN (online)	1876-7958
ISSN	1673-5374
DOI	10.4103/1673-5374.335830
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Article: Consensus clustering of gene expression profiles in peripheral blood of acute ischemic stroke patients.

Yang, Zhiyong / Wang, Guanghui / Luo, Nan / Tsang, Chi Kwan / Huang, Li'an

Frontiers in neurology

2022 Volume 13, Page(s) 937501

Abstract: Acute ischemic stroke (AIS) is a primary cause of mortality and morbidity worldwide. Currently, no clinically approved immune intervention is available for AIS treatment, partly due to the lack of relevant patient classification based on the peripheral ... ...

Abstract	Acute ischemic stroke (AIS) is a primary cause of mortality and morbidity worldwide. Currently, no clinically approved immune intervention is available for AIS treatment, partly due to the lack of relevant patient classification based on the peripheral immunity status of patients with AIS. In this study, we adopted the consensus clustering approach to classify patients with AIS into molecular subgroups based on the transcriptomic profiles of peripheral blood, and we identified three distinct AIS molecular subgroups and 8 modules in each subgroup by the weighted gene co-expression network analysis. Remarkably, the pre-ranked gene set enrichment analysis revealed that the co-expression modules with subgroup I-specific signature genes significantly overlapped with the differentially expressed genes in AIS patients with hemorrhagic transformation (HT). With respect to subgroup II, exclusively male patients with decreased proteasome activity were identified. Intriguingly, the majority of subgroup III was composed of female patients who showed a comparatively lower level of AIS-induced immunosuppression (AIIS). In addition, we discovered a non-linear relationship between female age and subgroup-specific gene expression, suggesting a gender- and age-dependent alteration of peripheral immunity. Taken together, our novel AIS classification approach could facilitate immunomodulatory therapies, including the administration of gender-specific therapeutics, and attenuation of the risk of HT and AIIS after ischemic stroke.
Language	English
Publishing date	2022-08-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2022.937501
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Article ; Online: Metal-loaded zeolites in ammonia decomposition catalysis.

Leung, Kwan Chee / Tan, Ephraem / Li, Guangchao / Ng, Bryan Kit Yue / Ho, Ping-Luen / Lebedev, Konstantin / Tsang, Shik Chi Edman

Faraday discussions

2023 Volume 243, Page(s) 520–548

Abstract: The viability of using ammonia as a hydrogen storage vector is contingent on the development of catalytic systems active for ammonia decomposition at low temperatures. Zeolite-supported metal catalysts, unlike systems based on supports like MgO or carbon ...

Abstract	The viability of using ammonia as a hydrogen storage vector is contingent on the development of catalytic systems active for ammonia decomposition at low temperatures. Zeolite-supported metal catalysts, unlike systems based on supports like MgO or carbon nanotubes (CNTs), are crystalline and lend themselves to analytic techniques like synchrotron X-ray powder diffraction (SXRD) and Rietveld refinement, allowing precise characterisation of catalytic active sites, and therefore mechanistic elucidation. This study focuses on characterising and optimising novel zeolite-supported Ru catalysts for ammonia decomposition, with a focus on the effects of N-substitution on catalyst structure and activity. Characterisation focuses on an unsubstituted and N-substituted Ru-zeolite Y pair with NMR, FTIR, TEM, XRD, XAS, ICP, and BET, demonstrating the successful incorporation of N into the zeolite framework and an enhancement in metal dispersion upon N-substitution. A series of 18 monometallic and bimetallic catalysts is then synthesised on X and USY supports and screened for catalytic activity. Ru is identified as the most active metal for ammonia decomposition. Observed trends suggest catalyst dispersion can be increased with substantially lower metal loadings, and in particular
Language	English
Publishing date	2023-07-19
Publishing country	England
Document type	Journal Article
ISSN	1364-5498
ISSN (online)	1364-5498
DOI	10.1039/d2fd00175f
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Article ; Online: How to use the Surveillance, Epidemiology, and End Results (SEER) data: research design and methodology.

Che, Wen-Qiang / Li, Yuan-Jie / Tsang, Chi-Kwan / Wang, Yu-Jiao / Chen, Zheng / Wang, Xiang-Yu / Xu, An-Ding / Lyu, Jun

Military Medical Research

2023 Volume 10, Issue 1, Page(s) 50

Abstract: In the United States (US), the Surveillance, Epidemiology, and End Results (SEER) program is the only comprehensive source of population-based information that includes stage of cancer at the time of diagnosis and patient survival data. This program aims ...

Abstract	In the United States (US), the Surveillance, Epidemiology, and End Results (SEER) program is the only comprehensive source of population-based information that includes stage of cancer at the time of diagnosis and patient survival data. This program aims to provide a database about cancer incidence and survival for studies of surveillance and the development of analytical and methodological tools in the cancer field. Currently, the SEER program covers approximately half of the total cancer patients in the US. A growing number of clinical studies have applied the SEER database in various aspects. However, the intrinsic features of the SEER database, such as the huge data volume and complexity of data types, have hindered its application. In this review, we provided a systematic overview of the commonly used methodologies and study designs for retrospective epidemiological research in order to illustrate the application of the SEER database. Therefore, the goal of this review is to assist researchers in the selection of appropriate methods and study designs for enhancing the robustness and reliability of clinical studies by mining the SEER database.
MeSH term(s)	Humans ; United States/epidemiology ; Retrospective Studies ; Reproducibility of Results ; Research Design ; SEER Program ; Neoplasms
Language	English
Publishing date	2023-10-31
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2768940-2
ISSN	2054-9369 ; 2054-9369
ISSN (online)	2054-9369
ISSN	2054-9369
DOI	10.1186/s40779-023-00488-2
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Article ; Online: Differences in Sleep Patterns and Mental Health Problems During Different Periods of COVID-19 Outbreak Among Community-Dwelling Older Men in Hong Kong.

Liao, Gengze / Huang, Bixia / Lee, Priscilla Ming / Zhao, Shi / Chan, Chi Kuen / Tai, Lai-Bun / Tsang, Chun Yuk Jason / Leung, Chi Chiu / Kwan, Mei-Po / Tse, Lap Ah

International journal of public health

2022 Volume 67, Page(s) 1604363

Abstract: Objectives: ...

Abstract	Objectives:
MeSH term(s)	Aged ; Anxiety/epidemiology ; COVID-19/epidemiology ; Cross-Sectional Studies ; Depression/epidemiology ; Disease Outbreaks ; Hong Kong/epidemiology ; Humans ; Independent Living ; Male ; Mental Health ; Pandemics ; SARS-CoV-2 ; Sleep ; Sleep Initiation and Maintenance Disorders/epidemiology
Language	English
Publishing date	2022-04-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2274130-6
ISSN	1661-8564 ; 1661-8556
ISSN (online)	1661-8564
ISSN	1661-8556
DOI	10.3389/ijph.2022.1604363
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Zs.A 843: Show issues

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Article ; Online: Review on the screening of urine glucose for early diagnosis of type 2 diabetes mellitus in school children and adolescents with obesity in Hong Kong.

Pang, Gloria Shir-Wey / Chung, Thomas Wai-Hung / Choy, Heather Hiu-Ting / Lee, Ching-Yin / Tung, Joanna Yuet-Ling / Fu, Antony Chun-Cheung / Tsang, Jennifer Wing-Yan / Yau, Ho-Chung / Belaramani, Kiran M / Wong, Lap-Ming / But, Betty Wai-Man / Chow, Jasmine Chi-Kwan / Wong, Shirley Man-Yee / Cheung, Patrick Chi-Hung / Lo, Priscilla Wai-Chee / Ng, Kwok-Leung / Poon, Sarah Wing-Yiu / Chan, Kwong Tat / Chan, Angela Mo-Kit /

Wong, Sammy Wai-Chun / Tay, Ming-Kut / Chung, Ying-Ki / Lam, Yuen-Yu / Kwan, Elaine Yin-Wah

Journal of pediatric endocrinology & metabolism : JPEM

2024 Volume 37, Issue 2, Page(s) 130–136

Abstract: Objectives: Obesity and type 2 diabetes mellitus (T2DM) are growing health concerns. Since 2005, Student Health Service (SHS) and Hong Kong Paediatric Society formulated a protocol on urine glucose screening (UGS) for early diagnosis of T2DM in students ...

Abstract	Objectives: Obesity and type 2 diabetes mellitus (T2DM) are growing health concerns. Since 2005, Student Health Service (SHS) and Hong Kong Paediatric Society formulated a protocol on urine glucose screening (UGS) for early diagnosis of T2DM in students with obesity in Hong Kong. This study reviews students with T2DM captured by this screening program and compare the data with the Hong Kong Children Diabetes Registry (HKCDR) database, to see if the UGS program facilitates early diagnosis of T2DM. Methods: Students between the ages of 10-18 years old with age- and sex-specific body mass index (BMI) >97th percentile who attended SHS between the school years from 2005/06 to 2017/18 were recruited for UGS. Those tested positive for random urine glucose underwent diagnostic testing for T2DM according to ADA guidelines. Demographic data and investigatory results from UGS and HKCDR within the same time period were compared. Results: A total of 216,526 students completed UGS in the said period; 415 (0.19 %) students were tested positive for urine glucose of which 121 students were diagnosed with T2DM. UGS picked up 23 % of the newly diagnosed T2DM cases. When compared to the HKCDR database, students diagnosed via UGS were significantly younger, less obese, and had fewer diabetic related complications. The negative predictive value of UGS is high and can effectively rule out T2DM. Conclusions: Urine glucose screening is an inexpensive and simple test that allows for early diagnosis of T2DM among obese school students. Other methods including POCT HbA
MeSH term(s)	Male ; Female ; Adolescent ; Humans ; Child ; Diabetes Mellitus, Type 2/diagnosis ; Diabetes Mellitus, Type 2/epidemiology ; Hong Kong/epidemiology ; Pediatric Obesity ; Glucose ; Diabetes Complications ; Early Diagnosis
Chemical Substances	Glucose (IY9XDZ35W2)
Language	English
Publishing date	2024-01-29
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1231070-0
ISSN	2191-0251 ; 0334-018X
ISSN (online)	2191-0251
ISSN	0334-018X
DOI	10.1515/jpem-2023-0295
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Zs.A 2258: Show issues

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Article ; Online: Harnessing Next-Generation Sequencing as a Timely and Accurate Second-Tier Screening Test for Newborn Screening of Inborn Errors of Metabolism.

Chan, Toby Chun Hei / Mak, Chloe Miu / Yeung, Matthew Chun Wing / Law, Eric Chun-Yiu / Cheung, Jana / Wong, Tsz Ki / Cheng, Vincent Wing-Sang / Lee, Jacky Kwan Ho / Wong, Jimmy Chi Lap / Fung, Cheuk Wing / Belaramani, Kiran Moti / Kwok, Anne Mei Kwun / Tsang, Kwok Yeung

International journal of neonatal screening

2024 Volume 10, Issue 1

Abstract: In this study, we evaluated the implementation of a second-tier genetic screening test using an amplicon-based next-generation sequencing (NGS) panel in our laboratory during the period of 1 September 2021 to 31 August 2022 for the newborn screening (NBS) ...

Abstract	In this study, we evaluated the implementation of a second-tier genetic screening test using an amplicon-based next-generation sequencing (NGS) panel in our laboratory during the period of 1 September 2021 to 31 August 2022 for the newborn screening (NBS) of six conditions for inborn errors of metabolism: citrullinemia type II (MIM #605814), systemic primary carnitine deficiency (MIM #212140), glutaric acidemia type I (MIM #231670), beta-ketothiolase deficiency (#203750), holocarboxylase synthetase deficiency (MIM #253270) and 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (MIM # 246450). The custom-designed NGS panel can detect sequence variants in the relevant genes and also specifically screen for the presence of the hotspot variant IVS16ins3kb of
Language	English
Publishing date	2024-03-05
Publishing country	Switzerland
Document type	Journal Article
ISSN	2409-515X
ISSN (online)	2409-515X
DOI	10.3390/ijns10010019
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