Publications by authors named "S K Chan"

8,111 Publications

Selective autophagy controls innate immune response through a TAK1/TAB2/SH3PX1 axis.

Cell Rep 2022 Jan;38(4):110286

School of Life Sciences, University of Warwick, CV4 7AL Coventry, UK. Electronic address:

Selective autophagy is a catabolic route that turns over specific cellular material for degradation by lysosomes, and whose role in the regulation of innate immunity is largely unexplored. Here, we show that the apical kinase of the Drosophila immune deficiency (IMD) pathway Tak1, as well as its co-activator Tab2, are both selective autophagy substrates that interact with the autophagy protein Atg8a. We also present a role for the Atg8a-interacting protein Sh3px1 in the downregulation of the IMD pathway, by facilitating targeting of the Tak1/Tab2 complex to the autophagy platform through its interaction with Tab2. Our findings show the Tak1/Tab2/Sh3px1 interactions with Atg8a mediate the removal of the Tak1/Tab2 signaling complex by selective autophagy. This in turn prevents constitutive activation of the IMD pathway in Drosophila. This study provides mechanistic insight on the regulation of innate immune responses by selective autophagy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2021.110286DOI Listing
January 2022

The Malaysian Society of Gastroenterology and Hepatology Consensus Statement on Metabolic Dysfunction-Associated Fatty Liver Disease.

J Gastroenterol Hepatol 2022 Jan 25. Epub 2022 Jan 25.

Gastroenterology Unit, Department of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.

Introduction: The Malaysian Society of Gastroenterology and Hepatology saw the need for a consensus statement on metabolic dysfunction-associated fatty liver disease (MAFLD).

Methods: The consensus panel consisted of experts in the field of gastroenterology/hepatology, endocrinology, bariatric surgery, family medicine and public health. A modified Delphi process was used to prepare the consensus statements.

Results: The panel recognized the high and increasing prevalence of the disease and the consequent anticipated increase in liver-related complications and mortality. Cardiovascular disease is the leading cause of mortality in MAFLD patients; therefore, cardiovascular disease risk assessment and management is important. A simple and clear liver assessment and referral pathway was agreed upon, so that patients with more severe MAFLD can be linked to gastroenterology/hepatology care, while patients with less severe MAFLD can remain in primary care or endocrinology, where they are best managed. Lifestyle intervention is the cornerstone in the management of MAFLD. The panel provided a consensus on the use of statin, angiotension-converting enzyme inhibitor or angiotensin receptor blocker, sodium glucose co-transporter-2 inhibitor, glucagon-like peptide-1 agonist, pioglitazone, vitamin E, and metformin; as well as recommendations on bariatric surgery, screening for gastro-esophageal varices and hepatocellular carcinoma, and liver transplantation in MAFLD patients. Increasing the awareness and knowledge of the various stakeholders on MAFLD and incorporating MAFLD into existing non-communicable diseases-related programs and activities are important steps to tackle the disease.

Conclusion: These consensus statements will serve as a guide on MAFLD for clinicians and other stakeholders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgh.15787DOI Listing
January 2022

Explicit and implicit mentalization of patients with first-episode schizophrenia: a study of self-referential gaze perception with eye movement analysis using hidden Markov models.

Eur Arch Psychiatry Clin Neurosci 2022 Jan 25. Epub 2022 Jan 25.

Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Room 219, New Clinical Building, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China.

Mentalizing impairment is one of the core features of schizophrenia, and bias judgement of others' gaze as self-directing is common to schizophrenia patients. In this case-control study, 30 patients with first-episode schizophrenia (FES) and 30 matched healthy controls were assigned gaze perception tasks with variable stimulus presentation times (300 ms and no time limit) to determine the presence of self-referential gaze perception (SRGP) bias. The eye movement pattern during the task were tracked and data were analysed using hidden Markov models (HMMs). The SRGP involves reporting of others' gaze intent and was used as a measurement of explicit mentalizing process. Eye movement measurement represents automated visual attention pattern and was considered as a measurement of implicit mentalizing process. The patients with FES had significantly more SRGP bias than the controls in the 300 ms condition but not in the no-time-limit condition. Social cognitive function was related to SRGP bias in the patient group. Two distinct eye movement patterns were identified: eye-focused and nose-focused. Significant group differences in eye movement patterns in the 300 ms condition were found with more controls had eye-focused pattern. Social anxiety symptoms were related to the nose-focused pattern, positive psychotic symptoms were related to the eye-focused pattern, and depressive symptoms were related to less consistent eye movement patterns. No significant relationship was found between SRGP bias and eye movement patterns. The dissociation between explicit and implicit mentalizing processes with different cognitive and symptom dimensions associated with the two processes suggests the presence of different mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00406-022-01383-yDOI Listing
January 2022

Total and differential white blood cell count and cause-specific mortality in 436 750 Taiwanese adults.

Nutr Metab Cardiovasc Dis 2021 Nov 15. Epub 2021 Nov 15.

Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR, China. Electronic address:

Background And Aims: White blood cell (WBC) count is an easily obtainable biomarker of systematic inflammation. Our study aimed to investigate the associations of differential WBC count with all-cause and cause-specific mortality in a general Asian population.

Methods And Results: Cox proportional hazards model was used to evaluate the associations of WBC count with mortality separately for men and women, with adjustment for multiple variables including age, smoking, and other lifestyle factors. Stratified analyses by age, smoking, diabetes, and hypertension were conducted to explore potential effect modification. Elevated WBC count was significantly associated with increased mortality risk. The adjusted hazard ratios of total WBC (10th decile compared to decile of lowest risk) for all-cause mortality were 1.42 (95% CI: 1.33, 1.53) for men and 1.54 (95% CI: 1.42, 1.68) for women. Similar risks were observed for neutrophils, monocytes, and neutrophil/lymphocyte (NL) ratio. The highest deciles of neutrophils, monocytes, and NL ratio were also positively associated with risk of cardiovascular/cerebrovascular, cancer, and respiratory mortality after adjusting for covariates. Results for all-cause mortality remained statistically significant for participants who were <60 years old, non-smokers, non-diabetic, and non-hypertensive.

Conclusions: Total and differential WBC counts (neutrophils, monocytes, and NL ratios) are positively associated with increased risk of all-cause mortality, cardiovascular and cerebrovascular, cancer, and respiratory mortality among Taiwanese adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.numecd.2021.11.004DOI Listing
November 2021

Post COVID-19 vaccine deaths - Singapore's early experience.

Forensic Sci Int 2022 Jan 19;332:111199. Epub 2022 Jan 19.

Forensic Medicine Division, Applied Sciences Group, Health Sciences Authority, Singapore.

Singapore has been using mRNA vaccines developed by Pfizer-BioNTech and Moderna as part of the nation's COVID vaccination program since 30 December 2020. From 1 February 2021-30 June 2021, a total of 34 deaths that occurred within 72 h of the deceased receiving their COVID-19 vaccination were referred to the Forensic Medicine Division of the Health Sciences Authority of Singapore. Autopsies, histological sampling and ancillary investigations consisting of total tryptase level, Immunoglobulin E (IgE), and C-reactive Protein (CRP), were performed on 29 of these cases. Our study has shown no definite causative relationship between the mRNA vaccination and deaths of individuals who died within 72 h after receiving the vaccination, in particular with regards to anaphylactic reactions, myocarditis and pericarditis, and thrombotic complications. Further studies may consider increasing the incident time frame from 72 h to seven days post-vaccination or longer to include any potential delayed presentation of adverse effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.forsciint.2022.111199DOI Listing
January 2022
-->