1.Romance of the three kingdoms: RORgammat allies with HIF1alpha against FoxP3 in regulating T cell metabolism and differentiation.
Andy TSUN ; Zuojia CHEN ; Bin LI
Protein & Cell 2011;2(10):778-781
Regulatory T (Treg) cells play an essential role in immune homeostasis by controlling the function of various immune effector cells, including RAR-related orphan receptor gammat(+) (RORγt(+)) T helper 17 (Th17) cells. Foekhead box P(3) (FoxP(3)) is the master regulator of Treg cell function, while RORγt is the key transcription factor for the induction of the interleukin (IL)-17 family of cytokines during Th17 cell differentiation. FoxP3 can directly interact with and negatively regulate the function of RORγt, to determine the balance between induced Treg (iTreg) and Th17 cell polarization. Two recent independent studies from the Pan and Chi Labs have shown how hypoxia-inducible factor 1 alpha (HIF1α) is able to tip the balance of T cell differentiation toward the Th17 lineage by responding to the local changes in metabolic shift or an increase in proinflammatory mediators in the microenvironment. By allying with HIF1α, RORγt wins the fight against FoxP3 and Treg cell commitment.
Animals
;
Cell Differentiation
;
Forkhead Transcription Factors
;
metabolism
;
Gene Expression Regulation
;
Humans
;
Hypoxia-Inducible Factor 1, alpha Subunit
;
metabolism
;
Immune System
;
cytology
;
metabolism
;
Nuclear Receptor Subfamily 1, Group F, Member 3
;
metabolism
;
T-Lymphocytes, Regulatory
;
metabolism
;
physiology
2.Medication adherence in inflammatory bowel disease.
Webber CHAN ; Andy CHEN ; Darren TIAO ; Christian SELINGER ; Rupert LEONG
Intestinal Research 2017;15(4):434-445
Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory condition with intestinal and extraintestinal manifestations. Medications are the cornerstone of treatment of IBD. However, patients often adhere to medication poorly. Adherence to medications is defined as the process by which patients take their medications as prescribed. Treatment non-adherence is a common problem among chronic diseases, averaging 50% in developed countries and is even poorer in developing countries. In this review, we will examine the adherence data in IBD which vary greatly depending on the study population, route of administration, and methods of adherence measurement used. We will also discuss the adverse clinical outcomes related to non-adherence to medical treatment including increased disease activity, flares, loss of response to anti-tumor necrosis factor therapy, and so forth. There are many methods to measure medication adherence namely direct and indirect methods, each with their advantages and drawbacks. Finally, we will explore different intervention strategies to improve adherence to medications.
Chronic Disease
;
Colitis, Ulcerative
;
Crohn Disease
;
Developed Countries
;
Developing Countries
;
Humans
;
Inflammatory Bowel Diseases*
;
Medication Adherence*
;
Necrosis
3.Model-based comparative prediction of transcription-factor binding motifs in anabolic responses in bone.
Andy B CHEN ; Kazunori HAMAMURA ; Guohua WANG ; Weirong XING ; Subburaman MOHAN ; Hiroki YOKOTA ; Yunlong LIU
Genomics, Proteomics & Bioinformatics 2007;5(3-4):158-165
Understanding the regulatory mechanism that controls the alteration of global gene expression patterns continues to be a challenging task in computational biology. We previously developed an ant algorithm, a biologically-inspired computational technique for microarray data, and predicted putative transcription-factor binding motifs (TFBMs) through mimicking interactive behaviors of natural ants. Here we extended the algorithm into a set of web-based software, Ant Modeler, and applied it to investigate the transcriptional mechanism underlying bone formation. Mechanical loading and administration of bone morphogenic proteins (BMPs) are two known treatments to strengthen bone. We addressed a question: Is there any TFBM that stimulates both "anabolic responses of mechanical loading" and "BMP-mediated osteogenic signaling"? Although there is no significant overlap among genes in the two responses, a comparative model-based analysis suggests that the two independent osteogenic processes employ common TFBMs, such as a stress responsive element and a motif for peroxisome proliferator-activated receptor (PPAR). The post-modeling in vitro analysis using mouse osteoblast cells supported involvements of the predicted TFBMs such as PPAR, Ikaros 3, and LMO2 in response to mechanical loading. Taken together, the results would be useful to derive a set of testable hypotheses and examine the role of specific regulators in complex transcriptional control of bone formation.
Algorithms
;
Animals
;
Base Sequence
;
Binding Sites
;
genetics
;
Biomechanical Phenomena
;
Bone Morphogenetic Proteins
;
pharmacology
;
Consensus Sequence
;
DNA
;
genetics
;
metabolism
;
Databases, Genetic
;
Gene Expression Profiling
;
statistics & numerical data
;
Genomics
;
statistics & numerical data
;
Mice
;
Oligonucleotide Array Sequence Analysis
;
statistics & numerical data
;
Osteoblasts
;
drug effects
;
metabolism
;
Osteogenesis
;
drug effects
;
genetics
;
physiology
;
Transcription Factors
;
metabolism
4.Medication non-adherence in inflammatory bowel diseases is associated with disability.
Jonathan PERRY ; Andy CHEN ; Viraj KARIYAWASAM ; Glen COLLINS ; Chee CHOONG ; Wei Ling TEH ; Nikola MITREV ; Friedbert KOHLER ; Rupert Wing Loong LEONG
Intestinal Research 2018;16(4):571-578
BACKGROUND/AIMS: Medication non-adherence is common in inflammatory bowel diseases (IBD). The short-term consequences of non-adherence include increased disease relapse but the long-term impact upon patients in terms of daily functional impairment are less well characterized. Identifying negative outcomes, such as disability, may encourage adherence. METHODS: Consecutive ambulatory IBD subjects completed the Medication Adherence Rating Scale (MARS; non-adherence defined as ≤16), Inflammatory Bowel Diseases Disability Index (IBD-DI; disability: < 3.5) and Beliefs about Medicines Questionnaire (high necessity/concerns: ≥16). The primary outcome was the association between medication non-adherence and disability. Secondary outcomes were the predictors of these outcomes. RESULTS: A total of 173 subjects on IBD maintenance medications were recruited (98 Crohn’s disease, 75 ulcerative colitis: median IBD-DI, –5.0; interquartile range [IQR], –14.0 to 4.0 and median MARS, 19.0; IQR, 18 to 20) of whom 24% were non-adherent. Disability correlated significantly with medication non-adherence (r=0.38, P < 0.0001). Median IBD-DI for non-adherers was significantly lower than adherers (–16.0 vs. –2.0, P < 0.0001). Predictors of disability included female sex (P=0.002), previous hospitalization (P=0.023), management in a referral hospital clinic (P=0.008) and medication concerns (P < 0.0001). Non-adherence was independently associated with difficulty managing bowel movements (odds ratio [OR], 3.71; 95% confidence interval [CI], 1.50–9.16, P=0.005), rectal bleeding (OR, 2.69; 95% CI, 1.14–6.36; P=0.024) and arthralgia/arthritis (OR, 2.56; 95% CI, 1.11–5.92; P=0.028). CONCLUSIONS: Medication non-adherence was associated with significantly increased disability in IBD. Female gender, higher disease severity and medication concerns were additional predictors of disability.
Colitis, Ulcerative
;
Compliance
;
Crohn Disease
;
Female
;
Hemorrhage
;
Hospitalization
;
Humans
;
Inflammatory Bowel Diseases*
;
Mars
;
Medication Adherence*
;
Recurrence
;
Referral and Consultation
5.Establishment and characterization of two new human embryonic stem cell lines, SYSU-1 and SYSU-2.
Guo HUANG ; Wei-qiang LI ; Rui CHEN ; Zhen-guang CHEN ; Xiu-ming ZHANG ; Fu-xiang MAO ; Shao-liang HUANG ; Shu-nong LI ; Bruce T LAHN ; Andy Peng XIANG
Chinese Medical Journal 2007;120(7):589-594
BACKGROUNDHuman embryonic stem cells can propagate indefinitely in vitro and are able to differentiate into derivatives of all three embryonic germ layers. The excitement surrounding human embryonic stem cells lies largely in their potential to produce specialized cells that can be used for transplant therapies. However, further investigation requires additional cell lines with varying genetic background. Therefore, efforts to derive and establish more human embryonic stem cell lines are highly warranted.
METHODSSurplus embryos (blastocysts) from donors were used to isolate the inner cell mass by immunosurgery. All cells were cultured continuously on irradiated murine embryonic fibroblasts feed layer and likely human embryonic stem cell colonies were subsequently characterized by cell surface marker staining, karyotyping and teratoma formation.
RESULTSTwo human embryonic stem cell lines (SYSU-1 and SYSU-2) were established from surplus embryos. The two lines express several pluripotency markers including alkaline phosphatase, SSEA-4, Tra-1-60, Oct-4, Nanog and Rex-1. They remain in undifferentiated state with normal karyotype after prolonged passages and can form embryoid bodies in vitro and teratoma in vivo.
CONCLUSIONTwo new human embryonic stem cell lines have been established from surplus embryos. They can be used to understand selfrenewal and differentiating mechanisms and provide more choices for regenerative medicine.
Cell Differentiation ; Cell Line ; Embryonic Stem Cells ; cytology ; Humans ; Karyotyping
6.The Gender-Sensitive Social Risk Factors for Internet Addiction in College Undergraduate Students
Xia LIN ; Jing-yan GU ; Wan-jun GUO ; Ya-jing MENG ; Hui-yao WANG ; Xiao-jing LI ; Wei DENG ; Lian-sheng ZHAO ; Xiao-hong MA ; Ming-li LI ; Ting CHEN ; Andy S.K. CHENG ; Tao LI
Psychiatry Investigation 2021;18(7):636-644
Objective:
The current study aims to explore precipitating and social risk factors for internet addiction (IA) in university undergraduate students, and to provide evidence for interventions and the early prevention of IA in different genders.
Methods:
Four thousand eight hundred and fifty-eight college sophomores completed an online survey on their internet use-related behaviours and social risk factors.
Results:
We found that more male (8.3%) than female students (5.4%) had moderate and severe IA. The main online activity in the moderate and severe IA groups was online gaming in males and online streaming in females. Roommates engaging in similar internetbased entertainment was a risk factor of IA only for males, while not being in a romantic relationship was a risk factor of IA for females only. Infatuation with the internet before college and adjustment problems for college life were shared risk factors for both genders in the mild and moderate IA groups.
Conclusion
IA was a common phenomenon in college students with shared and unique precipitating and social risk factors in males and females. The gender-sensitive risk factors for IA warranted earlier and individualized intervention and prevention strategies for IA in this population.
7.The Gender-Sensitive Social Risk Factors for Internet Addiction in College Undergraduate Students
Xia LIN ; Jing-yan GU ; Wan-jun GUO ; Ya-jing MENG ; Hui-yao WANG ; Xiao-jing LI ; Wei DENG ; Lian-sheng ZHAO ; Xiao-hong MA ; Ming-li LI ; Ting CHEN ; Andy S.K. CHENG ; Tao LI
Psychiatry Investigation 2021;18(7):636-644
Objective:
The current study aims to explore precipitating and social risk factors for internet addiction (IA) in university undergraduate students, and to provide evidence for interventions and the early prevention of IA in different genders.
Methods:
Four thousand eight hundred and fifty-eight college sophomores completed an online survey on their internet use-related behaviours and social risk factors.
Results:
We found that more male (8.3%) than female students (5.4%) had moderate and severe IA. The main online activity in the moderate and severe IA groups was online gaming in males and online streaming in females. Roommates engaging in similar internetbased entertainment was a risk factor of IA only for males, while not being in a romantic relationship was a risk factor of IA for females only. Infatuation with the internet before college and adjustment problems for college life were shared risk factors for both genders in the mild and moderate IA groups.
Conclusion
IA was a common phenomenon in college students with shared and unique precipitating and social risk factors in males and females. The gender-sensitive risk factors for IA warranted earlier and individualized intervention and prevention strategies for IA in this population.
8.Smartphone electrocardiogram for QT interval monitoring in Coronavirus Disease 2019 (COVID-19) patients treated with Hydroxychloroquine
Andy Tze Yang Ko ; Lean Seng Chen ; Ing Xiang Pang ; Hwei Sung Ling ; Tze Cheng Wong ; Tonnii Loong Loong Sia ; Keng Tat Koh
The Medical Journal of Malaysia 2021;76(2):125-130
Introduction: The global pandemic of Corona Virus Disease
2019 (COVID-19) has led to the re-purposing of medications,
such as hydroxychloroquine and lopinavir-ritonavir in the
treatment of the earlier phase of COVID-19 before the
recognized benefit of steroids and antiviral. We aim to
explore the corrected QT (QTc) interval and ‘torsadogenic’
potential of hydroxychloroquine and lopinavir-ritonavir
utilising a combination of smartphone electrocardiogram
and 12-lead electrocardiogram monitoring.
Materials and Methods: Between 16-April-2020 to 30-April2020, patients with suspected or confirmed for COVID-19
indicated for in-patient treatment with hydroxychloroquine
with or without lopinavir-ritonavir to the Sarawak General
Hospital were monitored with KardiaMobile smartphone
electrocardiogram (AliveCor®, Mountain View, CA) or
standard 12-lead electrocardiogram. The baseline and serial
QTc intervals were monitored till the last dose of
medications or until the normalization of the QTc interval.
Results: Thirty patients were treated with
hydroxychloroquine, and 20 (66.7%) patients received a
combination of hydroxychloroquine and lopinavir-ritonavir
therapy. The maximum QTc interval was significantly
prolonged compared to baseline (434.6±28.2msec vs.
458.6±47.1msec, p=0.001). The maximum QTc interval
(456.1±45.7msec vs. 464.6±45.2msec, p=0.635) and the delta
QTc (32.6±38.5msec vs. 26.3±35.8msec, p=0.658) were not
significantly different between patients on
hydroxychloroquine or a combination of
hydroxychloroquine and lopinavir-ritonavir. Five (16.7%)
patients had QTc of 500msec or more. Four (13.3%) patients
required discontinuation of hydroxychloroquine and 3
(10.0%) patients required discontinuation of lopinavirritonavir due to QTc prolongation. However, no torsade de
pointes was observed.
Conclusions: QTc monitoring using smartphone
electrocardiogram was feasible in COVID-19 patients treated
with hydroxychloroquine with or without lopinavir-ritonavir.
The usage of hydroxychloroquine and lopinavir-ritonavir
resulted in QTc prolongation, but no torsade de pointes or
arrhythmogenic death was observed.
9.A single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis.
Daoyuan HUANG ; Yuesheng ZUO ; Chen ZHANG ; Guoqiang SUN ; Ying JING ; Jinghui LEI ; Shuai MA ; Shuhui SUN ; Huifen LU ; Yusheng CAI ; Weiqi ZHANG ; Fei GAO ; Andy PENG XIANG ; Juan Carlos Izpisua BELMONTE ; Guang-Hui LIU ; Jing QU ; Si WANG
Protein & Cell 2023;14(12):888-907
The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.
Animals
;
Male
;
Testis
;
Sertoli Cells/metabolism*
;
Transcriptome
;
Spermatogenesis/genetics*
;
Primates
;
Aging/genetics*
;
Stem Cells
10.Prevalence of Autism Spectrum Disorder in China: A Nationwide Multi-center Population-based Study Among Children Aged 6 to 12 Years.
Hao ZHOU ; Xiu XU ; Weili YAN ; Xiaobing ZOU ; Lijie WU ; Xuerong LUO ; Tingyu LI ; Yi HUANG ; Hongyan GUAN ; Xiang CHEN ; Meng MAO ; Kun XIA ; Lan ZHANG ; Erzhen LI ; Xiaoling GE ; Lili ZHANG ; Chunpei LI ; Xudong ZHANG ; Yuanfeng ZHOU ; Ding DING ; Andy SHIH ; Eric FOMBONNE ; Yi ZHENG ; Jisheng HAN ; Zhongsheng SUN ; Yong-Hui JIANG ; Yi WANG
Neuroscience Bulletin 2020;36(9):961-971
This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder (ASD) in Chinese children. We targeted the population of 6 to 12-year-old children for this prevalence study by multistage convenient cluster sampling. The Modified Chinese Autism Spectrum Rating Scale was used for the screening process. Of the target population of 142,086 children, 88.5% (n = 125,806) participated in the study. A total of 363 children were confirmed as having ASD. The observed ASD prevalence rate was 0.29% (95% CI: 0.26%-0.32%) for the overall population. After adjustment for response rates, the estimated number of ASD cases was 867 in the target population sample, thereby achieving an estimated prevalence of 0.70% (95% CI: 0.64%-0.74%). The prevalence was significantly higher in boys than in girls (0.95%; 95% CI: 0.87%-1.02% versus 0.30%; 95% CI: 0.26%-0.34%; P < 0.001). Of the 363 confirmed ASD cases, 43.3% were newly diagnosed, and most of those (90.4%) were attending regular schools, and 68.8% of the children with ASD had at least one neuropsychiatric comorbidity. Our findings provide reliable data on the estimated ASD prevalence and comorbidities in Chinese children.