1.Neuronal plasticity of otolith-related vestibular system.
Suk-King LAI ; Chun-Hong LAI ; Fu-Xing ZHANG ; Chun-Wai MA ; Daisy K Y SHUM ; Ying-Shing CHAN
Acta Academiae Medicinae Sinicae 2008;30(6):741-746
This review focuses on our effort in addressing the development and lesion-induced plasticity of the gravity sensing system. After severance of sensory input from one inner ear, there is a bilateral imbalance in response dynamics and spatial coding behavior between neuronal subpopulations on the two sides. These data provide the basis for deranged spatial coding and motor deficits accompanying unilateral labyrinthectomy. Recent studies have also confirmed that both glutamate receptors and neurotrophin receptors within the bilateral vestibular nuclei are implicated in the plasticity during vestibular compensation and development. Changes in plasticity not only provide insight into the formation of a spatial map and recovery of vestibular function but also on the design of drugs for therapeutic strategies applicable to infants or vestibular disorders such as vertigo and dizziness.
Animals
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Humans
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Neuronal Plasticity
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Neurons
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physiology
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Otolithic Membrane
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innervation
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physiology
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Vestibule, Labyrinth
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innervation
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physiology
2.Development of neural correlates of linear motion in the rat vestibular nucleus.
Chun-Wai MA ; Chun-Hong LAI ; Lei HAN ; Daisy Kwok-Yan SHUM ; Ying-Shing CHAN
Acta Physiologica Sinica 2014;66(1):37-46
The capability of the central vestibular system in utilizing cues arising from the inner ear determines the ability of animals to acquire the sense of head orientations in the three-dimensional space and to shape postural movements. During development, neurons in the vestibular nucleus (VN) show significant changes in their electrophysiological properties. An age-dependent enhancement of membrane excitability is accompanied by a progressive increase in firing rate and discharge regularity. The coding of horizontal and vertical linear motions also exhibits developmental refinement in VN neurons. Further, modification of cell surface receptors, such as glutamate receptors, of developing VN neurons are well-orchestrated in the course of maturation, thereby regulating synaptic efficacy and spatial coding capacity of these neurons in local circuits. Taken together, these characteristic features of VN neurons contribute to developmental establishment of space-centered coordinates within the brain.
Animals
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Ear, Inner
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physiology
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Electrophysiological Phenomena
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Movement
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Neurons
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physiology
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Rats
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Receptors, Cell Surface
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physiology
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Vestibular Nuclei
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physiology
3.Molecular basis of von Hippel-Lindau syndrome in Chinese patients.
Wai-Kwan SIU ; Ronald Ching-Wan MA ; Ching-Wan LAM ; Chloe Miu MAK ; Yuet-Ping YUEN ; Fai-Man Ivan LO ; Kin-Wah CHAN ; Siu-Fung LAM ; Siu-Cheung LING ; Sui-Fan TONG ; Wing-Yee SO ; Chun-Chung CHOW ; Mary Hoi-Yin TANG ; Wing-Hung TAM ; Albert Yan-Wo CHAN
Chinese Medical Journal 2011;124(2):237-241
BACKGROUNDVon Hippel-Lindau (VHL) syndrome is an autosomal dominant familial cancer syndrome predisposing the affected individuals to multiple tumours in various organs. The genetic basis of VHL in Southern Chinese is largely unknown. In this study, we characterized the mutation spectrum of VHL in nine unrelated Southern Chinese families.
METHODSNine probands with clinical features of VHL, two symptomatic and eight asymptomatic family members were included in this study. Prenatal diagnosis was performed twice for one proband. Two probands had only isolated bilateral phaeochromocytoma. The VHL gene was screened for mutations by polymerase chain reaction, direct sequencing and multiplex ligation-dependent probe amplification (MLPA).
RESULTSThe nine probands and the two symptomatic family members carried heterozygous germline mutations. Eight different VHL mutations were identified in the nine probands. One splicing mutation, NM_000551.2: c.463+1G > T, was novel. The other seven VHL mutations, c.233A > G [p.Asn78Ser], c.239G > T [p.Ser80Ile], c.319C > G [p.Arg107Gly], c.481C > T [p.Arg161X], c.482G > A [p.Arg161Gln], c.499C > T [p.Arg167Trp] and an exon 2 deletion, had been previously reported. Three asymptomatic family members were positive for the mutation and the other five tested negative. In prenatal diagnosis, the fetuses were positive for the mutation.
CONCLUSIONSGenetic analysis could accurately confirm VHL syndrome in patients with isolated tumours such as sporadic phaeochromocytoma or epididymal papillary cystadenoma. Mutation detection in asymptomatic family members allows regular tumour surveillance and early intervention to improve their prognosis. DNA-based diagnosis can have an important impact on clinical management for VHL families.
Asian Continental Ancestry Group ; DNA Mutational Analysis ; Humans ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Von Hippel-Lindau Tumor Suppressor Protein ; genetics ; von Hippel-Lindau Disease ; genetics
4.Vision on the internationalization of physiology education: Trends and prospects.
Chun-Wai MA ; Kenneth Lap-Kei WU ; Ying-Shing CHAN
Acta Physiologica Sinica 2020;72(6):690-698
Rapid advancement of physiology education has occurred since the twentieth century due to the emergence of new pedagogies and collaborative effort of physiologists worldwide. Physiological organizations and institutions contribute to the teaching of physiology through international congresses, education symposia, teaching workshops, exchange programs, and journal publications. The Internet and information technologies play a crucial role in the promotion and improvement of computer-based physiology education across different countries. Interactive teaching practices and problem-based learning have also become globally applied strategies to enhance students' motivation and facilitate learning effectiveness. In this article, we review the global development and implementation of pedagogical approaches to the teaching of physiology, as well as the emerging trends and practices for physiology education in the future.
Humans
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Learning
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Motivation
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Physiology
5.Prostate health index can stratify patients with Prostate Imaging Reporting and Data System score 3 lesions on magnetic resonance imaging to reduce prostate biopsies.
John Shung-Lai LEUNG ; Wai-Kit MA ; Brian Sze-Ho HO ; Stacia Tsun-Tsun CHUN ; Rong NA ; Yongle ZHAN ; Chi-Yuen NG ; Chi-Ho IP ; Ada Tsui-Lin NG ; Yiu-Chung LAM
Asian Journal of Andrology 2023;26(1):20-24
We aim to evaluate prostate health index as an additional risk-stratification tool in patients with Prostate Imaging Reporting and Data System score 3 lesions on multiparametric magnetic resonance imaging. Men with biochemical or clinical suspicion of having prostate cancer who underwent multiparametric magnetic resonance imaging in two tertiary centers (Queen Mary Hospital and Princess Margaret Hospital, Hong Kong, China) between January 2017 and June 2022 were included. Ultrasound-magnetic resonance imaging fusion biopsies were performed after prostate health index testing. Those who only had Prostate Imaging Reporting and Data System score 3 lesions were further stratified into four prostate health index risk groups and the cancer detection rates were analyzed. Out of the 747 patients, 47.3% had Prostate Imaging Reporting and Data System score 3 lesions only. The detection rate of clinically significant prostate cancer in this group was 15.0%. The cancer detection rates of clinically significant prostate cancer had statistically significant differences: 5.3% in prostate health index <25.0, 7.4% in prostate health index 25.0-34.9, 17.9% in prostate health index 35.0-54.9, and 52.6% in prostate health index ≥55.0 (P < 0.01). Among the patients, 26.9% could have avoided a biopsy with a prostate health index <25.0, at the expense of a 5.3% risk of missing clinically significant prostate cancer. Prostate health index could be used as an additional risk stratification tool for patients with Prostate Imaging Reporting and Data System score 3 lesions. Biopsies could be avoided in patients with low prostate health index, with a small risk of missing clinically significant prostate cancer.
6.Inhibition of the CDK9-cyclin T1 protein-protein interaction as a new approach against triple-negative breast cancer.
Sha-Sha CHENG ; Yuan-Qing QU ; Jia WU ; Guan-Jun YANG ; Hao LIU ; Wanhe WANG ; Qi HUANG ; Feng CHEN ; Guodong LI ; Chun-Yuen WONG ; Vincent Kam Wai WONG ; Dik-Lung MA ; Chung-Hang LEUNG
Acta Pharmaceutica Sinica B 2022;12(3):1390-1405
Cyclin-dependent kinase 9 (CDK9) activity is correlated with worse outcomes of triple-negative breast cancer (TNBC) patients. The heterodimer between CDK9 with cyclin T1 is essential for maintaining the active state of the kinase and targeting this protein-protein interaction (PPI) may offer promising avenues for selective CDK9 inhibition. Herein, we designed and generated a library of metal complexes bearing the 7-chloro-2-phenylquinoline CˆN ligand and tested their activity against the CDK9-cyclin T1 PPI. Complex 1 bound to CDK9 via an enthalpically-driven binding mode, leading to disruption of the CDK9-cyclin T1 interaction in vitro and in cellulo. Importantly, complex 1 showed promising anti-metastatic activity against TNBC allografts in mice and was comparably active compared to cisplatin. To our knowledge, 1 is the first CDK9-cyclin T1 PPI inhibitor with anti-metastatic activity against TNBC. Complex 1 could serve as a new platform for the future design of more efficacious kinase inhibitors against cancer, including TNBC.