Publications by authors named "Y Ann Chen"

116,103 Publications

Changes in 6DOF knee kinematics during gait with decreasing gait speed.

Gait Posture 2021 Oct 8;91:52-58. Epub 2021 Oct 8.

Department of Orthopaedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong, China; School of Medicine, South China University of Technology, Guangzhou, 510006, China. Electronic address:

Background: Gait speed is recognized to correlate to knee kinematic alterations. Clinically, patients with knee diseases tend to walk slowly compared to healthy controls. Hence, gait speed may serve as a confounding factor in the kinematic characteristics of patients during gait compared to healthy controls.

Research Question: Whether and how gait speed affects six degrees of freedom (6DOF) knee kinematics remains unclear. The current study was designed to explore whether and how decreased gait speeds affect 6DOF knee kinematics.

Methods: Thirty subjects (15 males and 15 females) were recruited for this study. A three-dimensional gait analysis system was used to assess the 6DOF knee kinematics of subjects at gait speeds of 4.0 km/h, 3.5 km/h, 3.0 km/h, 2.5 km/h, 2.0 km/h, 1.5 km/h, and 1.0 km/h. Kinematics of gait cycle (GC) were assessed at all gait speed levels.

Results: Decreased adduction angle (0.5-3.2 °, p < 0.05), increased external rotation (0.6-3.3 °, p < 0.05) and decreased flexion angle (1.5-17.4 °, p < 0.05) were found during most GC as gait speed level decreased. Greater anterior tibial translation (0.9-2.6 mm, p < 0.05), greater proximal translation (0.4-2.4 mm, p < 0.05) and decreased lateral tibial translation (0.5-3.0 mm, p < 0.05) were found during most GC as gait speed level decreased. Gender was also found to have great effects on 6DOF knee kinematics (p < 0.05). Interactions between gender and gait speed were also found (p < 0.05).

Significance: Our findings suggest that additional attention should be paid when dealing with kinematic comparisons of GC between controls and patients with significantly different gait speeds or genders than controls. Kinematic alterations induced by gait speed may raise concern for patients with knee diseases who struggle to walk faster than their normal speed. This may enhance our knowledge of the relationship between gait speed and 6DOF knee kinematics.
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http://dx.doi.org/10.1016/j.gaitpost.2021.10.005DOI Listing
October 2021

Development of anti-breast cancer PI3K inhibitors based on 7-azaindole derivatives through scaffold hopping: Design, synthesis and in vitro biological evaluation.

Bioorg Chem 2021 Oct 6;117:105405. Epub 2021 Oct 6.

Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry, Fudan University, Shanghai 200433, China. Electronic address:

Breast cancer is the cancer with the highest incidence all over the world. Phosphatidylinositol 3-kinase is an important regulator of intracellular signaling pathways, which is frequently mutated and overexpressed in majority of human breast cancers, and the inhibition of PI3K has been considered as a promising approach for the treatment of the cancer. Here, we report our design and synthesis of new 7-azaindole derivatives as PI3K inhibitors through the scaffold hopping strategy. By varying the groups at the 3-position of 7-azaindole, we identified a series of potent PI3K inhibitors, whose antiproliferative activities against two human breast cancer MCF-7 and MDA-MB-231 cell lines were evaluated. Representative derivatives FD2054 and FD2078 showed better activity than BKM120 in antiproliferation, reduced the levels of phospho-AKT and induced cell apoptosis. All these results suggested that FD2054 and FD2078 are potent PI3K inhibitors that could be considered as potential candidates for the development of anticancer agents.
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http://dx.doi.org/10.1016/j.bioorg.2021.105405DOI Listing
October 2021

Investigating ABCD1 mutations in a Taiwanese cohort with hereditary spastic paraplegia phenotype.

Parkinsonism Relat Disord 2021 Oct 9;92:7-12. Epub 2021 Oct 9.

Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address:

Background: Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disorder caused by mutations in the ABCD1 gene. The clinical manifestations of ALD vary widely with some patients presenting with adrenomyeloneuropathy (AMN) that resembles the phenotype of hereditary spastic paraplegia (HSP). The aim of this study is to investigate the frequency, spectrum, and clinical features of ABCD1 mutations in Taiwanese patients with HSP phenotype.

Methods: Mutational analysis of the ABCD1 gene was performed in 230 unrelated Taiwanese patients with clinically suspected HSP by targeted resequencing. Clinical, electrophysiological, and neuroimaging features of the patients carrying an ABCD1 pathogenic mutation were characterized.

Results: Ten different ABCD1 mutations were identified in eleven patients, including two novel mutations (p.Q177Pfs*17 and p.Y357*) and eight ever reported in ALD cases of other ethnicities. All patients were male and exhibited slowly progressive spastic paraparesis with onset ages ranging from 21 to 50 years. Most of them had additional non-motor symptoms, including autonomic dysfunction in nine patients, sensory deficits in seven, premature baldness in seven, skin hyperpigmentation in five, psychiatric symptoms in one and cerebellar ataxia in one. Seven of the ten patients who ever received nerve conduction studies showed axonal polyneuropathy. Magnetic resonance imaging (MRI) revealed diffuse spinal cord atrophy in seven patients, cerebral white matter hyperintensity in one patient, and cerebellar involvement in one patient.

Conclusions: ABCD1 mutations account for 4.8% (11/230) of the cases with HSP phenotype in Taiwan. This study highlights the importance to consider ABCD1 mutations in patients with clinically suspected HSP of unknown genetic causes.
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http://dx.doi.org/10.1016/j.parkreldis.2021.10.006DOI Listing
October 2021

eIF3a R803K mutation mediates chemotherapy resistance by inducing cellular senescence in small cell lung cancer.

Pharmacol Res 2021 Oct 11:105934. Epub 2021 Oct 11.

Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, P. R. China; Institute of Clinical Pharmacology, Engineering Research Center for applied Technology of Pharmacogenomics of Ministry of Education, Central South University, Changsha 410078, P. R. China. Electronic address:

Drug resistance in small cell lung cancer (SCLC) significantly affects the efficacy of chemotherapy treatment. However, due to the lack of tumor tissue samples, especially serial tumor samples during chemotherapy, the mechanism of chemotherapy resistance has not been fully studied. Circulating tumor DNA, which can be obtained in a noninvasive manner, can complement tumor sampling approaches for research in this field. We identified an SCLC patient with acquired drug resistance from 52 SCLC patients for whom follow-up data were available. By comparing somatic mutations in circulating tumor DNA before and after chemotherapy, for the first time, we found that the somatic mutation eIF3A R803K may be related to acquired chemotherapy resistance. Then, the association between the eIF3A R803K mutation and chemotherapy resistance was confirmed by samples from 254 lung cancer patients receiving chemotherapy. We found that the eIF3a R803K mutation weakened the proliferation ability of tumor cells but increased their resistance to chemotherapy. Further studies revealed that the eIF3A R803K mutation promotes cellular senescence. In addition, fisetin showed a synergistic effect with chemotherapy in eIF3A R803K mutant cells. These results suggest that the eIF3A R803K somatic mutation has the potential to predict chemotherapy resistance in SCLC. Moreover, the eIF3A R803K mutation promotes chemotherapy resistance by inducing senescence. Furthermore, a senolytic drug, fisetin, can reverse chemotherapy resistance mediated by the eIF3A R803K mutation.
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http://dx.doi.org/10.1016/j.phrs.2021.105934DOI Listing
October 2021

Resveratrol and its derivative pterostilbene attenuate oxidative stress-induced intestinal injury by improving mitochondrial redox homeostasis and function via SIRT1 signaling.

Free Radic Biol Med 2021 Oct 11. Epub 2021 Oct 11.

College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China. Electronic address:

Oxidative stress inflicts mitochondrial dysfunction, which has been recognized as a key driver of intestinal diseases. Resveratrol (RSV) and its derivative pterostilbene (PTS) are natural antioxidants and exert a protective influence on intestinal health. However, the therapeutic effects and mechanisms of RSV and PTS on oxidative stress-induced mitochondrial dysfunction and intestinal injury remain unclear. The present study used porcine and cellular settings to compare the effects of RSV and PTS on mitochondrial redox homeostasis and function to alleviate oxidative stress-induced intestinal injury. Our results indicated that PTS was more potent than RSV in reducing oxidative stress, maintaining intestinal integrity, and preserving the mitochondrial function of diquat-challenged piglets. In the in vitro study, RSV and PTS protected against hydrogen peroxide (HO)-induced mitochondrial dysfunction in intestinal porcine enterocyte cell line (IPEC-J2) by facilitating mitochondrial biogenesis and increasing the activities of mitochondrial complexes. In addition, both RSV and PTS efficiently mitigated mitochondrial oxidative stress by increasing sirtuin 3 protein expression and the deacetylation of superoxide dismutase 2 and peroxiredoxin 3 in HO-exposed IPEC-J2 cells. Furthermore, RSV and PTS preserved mitochondrial membrane potential, which restrained the release of cytochrome C from mitochondria to the cytoplasm and caspase-3 activation and further reduced apoptotic rates in HOexposed IPEC-J2 cells. Mechanistically, depletion of sirtuin 1 (SIRT1) abrogated RSV's and PTS's benefits against mitochondrial reactive oxygen species (mtROS) overproduction, mitochondrial dysfunction, and apoptosis in HO-exposed IPEC-J2 cells, suggesting that SIRT1 was required for RSV and PTS to protect against oxidative stress-induced intestinal injury. In conclusion, RSV and PTS improve oxidative stress-induced intestinal injury by regulating mitochondrial redox homeostasis and function via SIRT1 signaling pathway. In offering this protection, PTS is superior to RSV.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.10.011DOI Listing
October 2021
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