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Amidst infectious disease outbreaks, a practical tool that can quantitatively monitor individuals’ antibodies to pathogens is vital for disease control. The currently used serological lateral flow immunoassays (LFIAs) can only detect the presence of antibodies for a single antigen. Here, we fabricated a multiplexed circular flow immunoassay (CFIA) test strip with YOLO v4-based object recognition that can quickly quantify and differentiate antibodies that bind membrane glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or hemagglutinin of influenza A (H1N1) virus in the sera of immunized mice in one assay using one sample. Spot intensities were found to be indicative of antibody titers to membrane glycoprotein of SARS-CoV-2 and were, thus, quantified relative to spots from immunoglobulin G (IgG) reaction in a CFIA to account for image heterogeneity. Quantitative intensities can be displayed in real time alongside an image of CFIA that was captured by a built-in camera. We demonstrate for the first time that CFIA is a specific, multi-target, and quantitative tool that holds potential for digital and simultaneous monitoring of antibodies recognizing various pathogens including SARS-CoV-2.
Ryan Yuki Huang; Deron Raymond Herr. Quantitative circular flow immunoassays with trained object recognition to detect antibodies to SARS-CoV-2 membrane glycoprotein. Biochemical and Biophysical Research Communications 2021, 565, 8 -13.
AMA StyleRyan Yuki Huang, Deron Raymond Herr. Quantitative circular flow immunoassays with trained object recognition to detect antibodies to SARS-CoV-2 membrane glycoprotein. Biochemical and Biophysical Research Communications. 2021; 565 ():8-13.
Chicago/Turabian StyleRyan Yuki Huang; Deron Raymond Herr. 2021. "Quantitative circular flow immunoassays with trained object recognition to detect antibodies to SARS-CoV-2 membrane glycoprotein." Biochemical and Biophysical Research Communications 565, no. : 8-13.
Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid which modulates vascular integrity through its receptors, S1P1–S1P5. Notably, S1P2 has been shown to mediate the disruption of cerebrovascular integrity in vitro and in vivo. However, the mechanism underlying this process has not been fully elucidated. We evaluated the role of S1P2 in blood-brain barrier (BBB) disruption induced by lipopolysaccharide (LPS)-mediated systemic inflammation and found that BBB disruption and neutrophil infiltration were significantly attenuated in S1pr2−/− mice relative to S1pr2+/− littermates. This is concomitant with attenuation of LPS-induced transcriptional activation of IL-6 and downregulation of occludin. Furthermore, S1pr2−/− mice had significantly reduced expression of genes essential for neutrophil infiltration: Sele, Cxcl1, and Cxcl2. Conversely, pharmacological agonism of S1P2 induced transcriptional activation of E-selectin in vitro and in vivo. Although S1P2 does not appear to be required for activation of microglia, stimulation of microglial cells with the S1P2 potentiated the response of endothelial cells to LPS. These results demonstrate that S1P2 promotes LPS-induced neutrophil extravasation by inducing expression of endothelial adhesion molecule gene, Sele, and potentiating microglial inflammation of endothelial cells. It is likely that S1P2 is a mediator of cerebrovascular inflammation and represents a potential therapeutic target for neurodegenerative disease such as vascular cognitive impairment.
Ping Xiang; Wee Siong Chew; Wei Lun Seow; Brenda Wan Shing Lam; Wei-Yi Ong; Deron R. Herr. The S1P2 receptor regulates blood-brain barrier integrity and leukocyte extravasation with implications for neurodegenerative disease. Neurochemistry International 2021, 146, 105018 .
AMA StylePing Xiang, Wee Siong Chew, Wei Lun Seow, Brenda Wan Shing Lam, Wei-Yi Ong, Deron R. Herr. The S1P2 receptor regulates blood-brain barrier integrity and leukocyte extravasation with implications for neurodegenerative disease. Neurochemistry International. 2021; 146 ():105018.
Chicago/Turabian StylePing Xiang; Wee Siong Chew; Wei Lun Seow; Brenda Wan Shing Lam; Wei-Yi Ong; Deron R. Herr. 2021. "The S1P2 receptor regulates blood-brain barrier integrity and leukocyte extravasation with implications for neurodegenerative disease." Neurochemistry International 146, no. : 105018.
Sphingolipid concentrations have been associated with risk of type 2 diabetes and cardiovascular diseases. Because sphingolipids can be synthesized de novo from saturated fatty acids (SFA), dietary fatty acids may affect plasma sphingolipid concentrations. We aimed to evaluate dietary fat and protein intakes in relation to circulating sphingolipid levels. We used cross-sectional data from 2860 ethnic Chinese Singaporeans collected from 2004–2007. Nutrient intakes were estimated on the basis of a validated 159-item food frequency questionnaire. We quantified 79 molecularly distinct sphingolipids in a large-scale lipidomic evaluation from plasma samples. Higher saturated fat intake was associated with higher concentrations of 16:1;O2 sphingolipids including ceramides, monohexosylcermides, dihexosylceramides, sphingomyelins, and sphingosine 1-phosphates. Higher polyunsaturated fat intake was associated with lower plasma long-chain ceramides and long-chain monohexosylcermide concentrations. Protein intake was inversely associated with concentrations of most subclasses of sphingolipids, with the exception of sphingolipids containing a 16:1;O2 sphingoid base. Lower intake of saturated fat and higher intake of polyunsaturated fat and protein may decrease plasma concentrations of several sphingolipid classes. These findings may represent a novel biological mechanism for the impact of nutrient intakes on cardio-metabolic health.
Jowy Seah; Wee Chew; Federico Torta; Chin Khoo; Markus Wenk; Deron Herr; E. Tai; Rob van Dam. Dietary Fat and Protein Intake in Relation to Plasma Sphingolipids as Determined by a Large-Scale Lipidomic Analysis. Metabolites 2021, 11, 93 .
AMA StyleJowy Seah, Wee Chew, Federico Torta, Chin Khoo, Markus Wenk, Deron Herr, E. Tai, Rob van Dam. Dietary Fat and Protein Intake in Relation to Plasma Sphingolipids as Determined by a Large-Scale Lipidomic Analysis. Metabolites. 2021; 11 (2):93.
Chicago/Turabian StyleJowy Seah; Wee Chew; Federico Torta; Chin Khoo; Markus Wenk; Deron Herr; E. Tai; Rob van Dam. 2021. "Dietary Fat and Protein Intake in Relation to Plasma Sphingolipids as Determined by a Large-Scale Lipidomic Analysis." Metabolites 11, no. 2: 93.
Sphingolipids (SPs) are structurally diverse and represent one of the most quantitatively abundant classes of lipids in mammalian cells. In addition to their structural roles, many SP species are known to be bioactive mediators of essential cellular processes. Historically, studies have focused on SP species that contain the canonical 18‑carbon, mono-unsaturated sphingoid backbone. However, increasingly sensitive analytical technologies, driven by advances in mass spectrometry, have facilitated the identification of previously under-appreciated, molecularly distinct SP species. Many of these less abundant species contain noncanonical backbones. Interestingly, a growing number of studies have identified clinical associations between these noncanonical SPs and disease, suggesting that there is functional significance to the alteration of SP backbone structure. For example, associations have been found between SP chain length and cardiovascular disease, pain, diabetes, and dementia. This review will provide an overview of the processes that are known to regulate noncanonical SP accumulation, describe the clinical correlations reported for these molecules, and review the experimental evidence for the potential functional implications of their dysregulation. It is likely that further scrutiny of noncanonical SPs may provide new insight into pathophysiological processes, serve as useful biomarkers for disease, and lead to the design of novel therapeutic strategies.
Brenda Wan Shing Lam; Ting Yu Amelia Yam; Christopher P. Chen; Mitchell K.P. Lai; Wei-Yi Ong; Deron R. Herr. The noncanonical chronicles: Emerging roles of sphingolipid structural variants. Cellular Signalling 2020, 79, 109890 .
AMA StyleBrenda Wan Shing Lam, Ting Yu Amelia Yam, Christopher P. Chen, Mitchell K.P. Lai, Wei-Yi Ong, Deron R. Herr. The noncanonical chronicles: Emerging roles of sphingolipid structural variants. Cellular Signalling. 2020; 79 ():109890.
Chicago/Turabian StyleBrenda Wan Shing Lam; Ting Yu Amelia Yam; Christopher P. Chen; Mitchell K.P. Lai; Wei-Yi Ong; Deron R. Herr. 2020. "The noncanonical chronicles: Emerging roles of sphingolipid structural variants." Cellular Signalling 79, no. : 109890.
Sphingosine 1-phosphates (S1Ps) are bioactive lipids that mediate a diverse range of effects through the activation of cognate receptors, S1P1–S1P5. Scrutiny of S1P-regulated pathways over the past three decades has identified important and occasionally counteracting functions in the brain and cerebrovascular system. For example, while S1P1 and S1P3 mediate proinflammatory effects on glial cells and directly promote endothelial cell barrier integrity, S1P2 is anti-inflammatory but disrupts barrier integrity. Cumulatively, there is significant preclinical evidence implicating critical roles for this pathway in regulating processes that drive cerebrovascular disease and vascular dementia, both being part of the continuum of vascular cognitive impairment (VCI). This is supported by clinical studies that have identified correlations between alterations of S1P and cognitive deficits. We review studies which proposed and evaluated potential mechanisms by which such alterations contribute to pathological S1P signaling that leads to VCI-associated chronic neuroinflammation and neurodegeneration. Notably, S1P receptors have divergent but overlapping expression patterns and demonstrate complex interactions. Therefore, the net effect produced by S1P represents the cumulative contributions of S1P receptors acting additively, synergistically, or antagonistically on the neural, vascular, and immune cells of the brain. Ultimately, an optimized therapeutic strategy that targets S1P signaling will have to consider these complex interactions.
Xin Ying Chua; Leona T. Y. Ho; Ping Xiang; Wee Siong Chew; Brenda Wan Shing Lam; Christopher P. Chen; Wei-Yi Ong; Mitchell K. P. Lai; Deron R. Herr. Preclinical and Clinical Evidence for the Involvement of Sphingosine 1-Phosphate Signaling in the Pathophysiology of Vascular Cognitive Impairment. NeuroMolecular Medicine 2020, 23, 47 -67.
AMA StyleXin Ying Chua, Leona T. Y. Ho, Ping Xiang, Wee Siong Chew, Brenda Wan Shing Lam, Christopher P. Chen, Wei-Yi Ong, Mitchell K. P. Lai, Deron R. Herr. Preclinical and Clinical Evidence for the Involvement of Sphingosine 1-Phosphate Signaling in the Pathophysiology of Vascular Cognitive Impairment. NeuroMolecular Medicine. 2020; 23 (1):47-67.
Chicago/Turabian StyleXin Ying Chua; Leona T. Y. Ho; Ping Xiang; Wee Siong Chew; Brenda Wan Shing Lam; Christopher P. Chen; Wei-Yi Ong; Mitchell K. P. Lai; Deron R. Herr. 2020. "Preclinical and Clinical Evidence for the Involvement of Sphingosine 1-Phosphate Signaling in the Pathophysiology of Vascular Cognitive Impairment." NeuroMolecular Medicine 23, no. 1: 47-67.
Clinacanthus nutans (Lindau) (C. nutans) has diverse uses in traditional herbal medicine for treating skin rashes, insect and snake bites, lesions caused by herpes simplex virus, diabetes mellitus and gout in Singapore, Malaysia, Indonesia, Thailand and China. We previously showed that C. nutans has the ability to modulate the induction of cytosolic phospholipase A2 (cPLA2) expression in SH-SY5Y cells through the inhibition of histone deacetylases (HDACs). In the current study, we elucidated the effect of C. nutans on the hCMEC/D3 human brain endothelial cell line. Endothelial cells are exposed to high levels of the cholesterol oxidation product, 7-ketocholesterol (7KC), in patients with cardiovascular disease and diabetes, and this process is thought to mediate pathological inflammation. 7KC induced a dose-dependent loss of hCMEC/D3 cell viability, and such damage was significantly inhibited by C. nutans leaf extracts but not stem extracts. 7KC also induced a marked increase in mRNA expression of pro-inflammatory cytokines, IL-1β IL-6, IL-8, TNF-α and cyclooxygenase-2 (COX-2) in brain endothelial cells, and these increases were significantly inhibited by C. nutans leaf but not stem extracts. HPLC analyses showed that leaf extracts have a markedly different chemical profile compared to stem extracts, which might explain their different effects in counteracting 7KC-induced inflammation. Further study is necessary to identify the putative phytochemicals in C. nutans leaves that have anti-inflammatory properties.
Xuan Kuo; Deron R. Herr; Wei-Yi Ong. Anti-inflammatory and Cytoprotective Effect of Clinacanthus nutans Leaf But Not Stem Extracts on 7-Ketocholesterol Induced Brain Endothelial Cell Injury. NeuroMolecular Medicine 2020, 23, 176 -183.
AMA StyleXuan Kuo, Deron R. Herr, Wei-Yi Ong. Anti-inflammatory and Cytoprotective Effect of Clinacanthus nutans Leaf But Not Stem Extracts on 7-Ketocholesterol Induced Brain Endothelial Cell Injury. NeuroMolecular Medicine. 2020; 23 (1):176-183.
Chicago/Turabian StyleXuan Kuo; Deron R. Herr; Wei-Yi Ong. 2020. "Anti-inflammatory and Cytoprotective Effect of Clinacanthus nutans Leaf But Not Stem Extracts on 7-Ketocholesterol Induced Brain Endothelial Cell Injury." NeuroMolecular Medicine 23, no. 1: 176-183.
Ergothioneine (ET) is a naturally occurring antioxidant that is synthesized by non-yeast fungi and certain bacteria. ET is not synthesized by animals, including humans, but is avidly taken up from the diet, especially from mushrooms. In the current study, we elucidated the effect of ET on the hCMEC/D3 human brain endothelial cell line. Endothelial cells are exposed to high levels of the cholesterol oxidation product, 7-ketocholesterol (7KC), in patients with cardiovascular disease and diabetes, and this process is thought to mediate pathological inflammation. 7KC induces a dose-dependent loss of cell viability and an increase in apoptosis and necrosis in the endothelial cells. A relocalization of the tight junction proteins, zonula occludens-1 (ZO-1) and claudin-5, towards the nucleus of the cells was also observed. These effects were significantly attenuated by ET. In addition, 7KC induces marked increases in the mRNA expression of pro-inflammatory cytokines, IL-1β IL-6, IL-8, TNF-α and cyclooxygenase-2 (COX2), as well as COX2 enzymatic activity, and these were significantly reduced by ET. Moreover, the cytoprotective and anti-inflammatory effects of ET were significantly reduced by co-incubation with an inhibitor of the ET transporter, OCTN1 (VHCL). This shows that ET needs to enter the endothelial cells to have a protective effect and is unlikely to act via extracellular neutralizing of 7KC. The protective effect on inflammation in brain endothelial cells suggests that ET might be useful as a nutraceutical for the prevention or management of neurovascular diseases, such as stroke and vascular dementia. Moreover, the ability of ET to cross the blood-brain barrier could point to its usefulness in combatting 7KC that is produced in the CNS during neuroinflammation, e.g. after excitotoxicity, in chronic neurodegenerative diseases, and possibly COVID-19-related neurologic complications.
Sally Shuxian Koh; Samantha Chia-Yi Ooi; Natalie Man-Yin Lui; Cao Qiong; Leona Ting-Yuke Ho; Irwin Kee-Mun Cheah; Barry Halliwell; Deron R. Herr; Wei-Yi Ong. Effect of Ergothioneine on 7-Ketocholesterol-Induced Endothelial Injury. NeuroMolecular Medicine 2020, 23, 184 -198.
AMA StyleSally Shuxian Koh, Samantha Chia-Yi Ooi, Natalie Man-Yin Lui, Cao Qiong, Leona Ting-Yuke Ho, Irwin Kee-Mun Cheah, Barry Halliwell, Deron R. Herr, Wei-Yi Ong. Effect of Ergothioneine on 7-Ketocholesterol-Induced Endothelial Injury. NeuroMolecular Medicine. 2020; 23 (1):184-198.
Chicago/Turabian StyleSally Shuxian Koh; Samantha Chia-Yi Ooi; Natalie Man-Yin Lui; Cao Qiong; Leona Ting-Yuke Ho; Irwin Kee-Mun Cheah; Barry Halliwell; Deron R. Herr; Wei-Yi Ong. 2020. "Effect of Ergothioneine on 7-Ketocholesterol-Induced Endothelial Injury." NeuroMolecular Medicine 23, no. 1: 184-198.
Background There has been ongoing research impetus to uncover novel blood-based diagnostic and prognostic biomarkers for Alzheimer’s disease (AD), vascular dementia (VaD), and related cerebrovascular disease (CEVD)-associated conditions within the spectrum of vascular cognitive impairment (VCI). Sphingosine-1-phosphates (S1Ps) are signaling lipids which act on the S1PR family of cognate G-protein-coupled receptors and have been shown to modulate neuroinflammation, a process known to be involved in both neurodegenerative and cerebrovascular diseases. However, the status of peripheral S1P in AD and VCI is at present unclear. Methods We obtained baseline bloods from individuals recruited into an ongoing longitudinal cohort study who had normal cognition (N = 80); cognitive impairment, no dementia (N = 160); AD (N = 113); or VaD (N = 31), along with neuroimaging assessments of cerebrovascular diseases. Plasma samples were processed for the measurements of major S1P species: d16:1, d17:1, d18:0, and d18:1, along with pro-inflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF). Furthermore, in vitro effects of S1Ps on cytokine expression were also studied in an astrocytoma cell line and in rodent primary astrocytes. Results Of the S1Ps species measured, only d16:1 S1P was significantly reduced in the plasma of VaD, but not AD, patients, while the d18:1 to d16:1 ratios were increased in all cognitive subgroups (CIND, AD, and VaD). Furthermore, d18:1 to d16:1 ratios correlated with levels of IL-6, IL-8, and TNF. In both primary astrocytes and an astroglial cell line, treatment with d16:1 or d18:1 S1P resulted in the upregulation of mRNA transcripts of pro-inflammatory cytokines, with d18:1 showing a stronger effect than d16:1. Interestingly, co-treatment assays showed that the addition of d16:1 reduced the extent of d18:1-mediated gene expression, indicating that d16:1 may function to “fine-tune” the pro-inflammatory effects of d18:1. Conclusion Taken together, our data suggest that plasma d16:1 S1P may be useful as a diagnostic marker for VCI, while the d18:1 to d16:1 S1P ratio is an index of dysregulated S1P-mediated immunomodulation leading to chronic inflammation-associated neurodegeneration and cerebrovascular damage.
Xin Ying Chua; Yuek Ling Chai; Wee Siong Chew; Joyce R. Chong; Hui Li Ang; Ping Xiang; Kaddy Camara; Amy R. Howell; Federico Torta; Markus R. Wenk; Saima Hilal; Narayanaswamy Venketasubramanian; Christopher P. Chen; Deron R. Herr; Mitchell K. P. Lai. Immunomodulatory sphingosine-1-phosphates as plasma biomarkers of Alzheimer’s disease and vascular cognitive impairment. Alzheimer's Research & Therapy 2020, 12, 1 -12.
AMA StyleXin Ying Chua, Yuek Ling Chai, Wee Siong Chew, Joyce R. Chong, Hui Li Ang, Ping Xiang, Kaddy Camara, Amy R. Howell, Federico Torta, Markus R. Wenk, Saima Hilal, Narayanaswamy Venketasubramanian, Christopher P. Chen, Deron R. Herr, Mitchell K. P. Lai. Immunomodulatory sphingosine-1-phosphates as plasma biomarkers of Alzheimer’s disease and vascular cognitive impairment. Alzheimer's Research & Therapy. 2020; 12 (1):1-12.
Chicago/Turabian StyleXin Ying Chua; Yuek Ling Chai; Wee Siong Chew; Joyce R. Chong; Hui Li Ang; Ping Xiang; Kaddy Camara; Amy R. Howell; Federico Torta; Markus R. Wenk; Saima Hilal; Narayanaswamy Venketasubramanian; Christopher P. Chen; Deron R. Herr; Mitchell K. P. Lai. 2020. "Immunomodulatory sphingosine-1-phosphates as plasma biomarkers of Alzheimer’s disease and vascular cognitive impairment." Alzheimer's Research & Therapy 12, no. 1: 1-12.
Endogenous alcohol produced by the gut microbiome is transported via the bloodstream to the liver for detoxification. Gut dysbiosis can result in chronic excess alcohol production that contributes to the development of hepatic steatosis. The aim of this study was to examine whether linolenic acid can manipulate the production of harmful alcohol and beneficial short-chain fatty acids (SCFAs) in the metabolome of commensal Klebsiella pneumoniae (K. pneumoniae) and the virulent K. pneumoniae K1 serotype. Glucose fermentation by the K. pneumoniae K1 serotype yielded increased production of alcohol and decreased SCFAs (especially acetate and propionate) compared to those of commensal K. pneumoniae. However, the use of linolenic acid instead of glucose significantly reduced alcohol and increased SCFAs in the fermentation media of the K. pneumoniae K1 serotype. The work highlights the value of shaping the microbial metabolome using linolenic acid, which can potentially regulate the gut–liver axis for the prevention and treatment of alcohol-induced liver diseases.
Ryan Yuki Huang; Deron Raymond Herr; Shabbir Moochhala. Manipulation of Alcohol and Short-Chain Fatty Acids in the Metabolome of Commensal and Virulent Klebsiella pneumoniae by Linolenic Acid. Microorganisms 2020, 8, 773 .
AMA StyleRyan Yuki Huang, Deron Raymond Herr, Shabbir Moochhala. Manipulation of Alcohol and Short-Chain Fatty Acids in the Metabolome of Commensal and Virulent Klebsiella pneumoniae by Linolenic Acid. Microorganisms. 2020; 8 (5):773.
Chicago/Turabian StyleRyan Yuki Huang; Deron Raymond Herr; Shabbir Moochhala. 2020. "Manipulation of Alcohol and Short-Chain Fatty Acids in the Metabolome of Commensal and Virulent Klebsiella pneumoniae by Linolenic Acid." Microorganisms 8, no. 5: 773.
Pruritus and inflammation associated with accumulation of calcium phosphate (CaP) under the skin are common problems among dialysis patients with chronic kidney disease (CKD). The role of skin commensal microbiota in the CaP-induced uremic pruritus remains uncharacterized. Skin Cutibacterium acnes (C. acnes) can solubilize CaP by the production of short-chain fatty acids (SCFAs), such as butyric acid, through glucose fermentation. Like butyric acid, the N-[2-(2-Butyrylamino-ethoxy)-ethyl]-butyramide (BA-NH-NH-BA), a butyric acid derivative, remarkably induced acetylation of histone H3 lysine 9 (AcH3K9) in keratinocytes. Topical application of fermenting C. acnes, butyric acid or BA-NH-NH-BA onto mouse skin effectively ameliorated CaP-induced skin itching, interleukin (IL)-6 up-regulation in keratinocytes, and extracellular signal-regulated kinase (ERK) 1/2 activation in dorsal root ganglia (DRG). Activation of ERK 1/2 by CaP was markedly reduced in IL-6 knockout mice. Genus Cutibacterium was detected in relatively low abundance in itchy skin of patients with CKD. Our results identify a role for the skin fermenting C. acnes in ameliorating CaP-induced activation of IL-6/p-ERK signaling and resulting skin inflammation. Furthermore, we provide evidence for the potential therapeutic efficacy of BA-NH-NH-BA as a postbiotic for the treatment of uremic pruritus.
Sunita Keshari; Yanhan Wang; Deron Raymond Herr; Sung-Min Wang; Wu-Chang Yang; Tsung-Hsien Chuang; Chien-Lung Chen. Skin Cutibacterium acnes Mediates Fermentation to Suppress the Calcium Phosphate-Induced Itching: A Butyric Acid Derivative with Potential for Uremic Pruritus. Journal of Clinical Medicine 2020, 9, 312 .
AMA StyleSunita Keshari, Yanhan Wang, Deron Raymond Herr, Sung-Min Wang, Wu-Chang Yang, Tsung-Hsien Chuang, Chien-Lung Chen. Skin Cutibacterium acnes Mediates Fermentation to Suppress the Calcium Phosphate-Induced Itching: A Butyric Acid Derivative with Potential for Uremic Pruritus. Journal of Clinical Medicine. 2020; 9 (2):312.
Chicago/Turabian StyleSunita Keshari; Yanhan Wang; Deron Raymond Herr; Sung-Min Wang; Wu-Chang Yang; Tsung-Hsien Chuang; Chien-Lung Chen. 2020. "Skin Cutibacterium acnes Mediates Fermentation to Suppress the Calcium Phosphate-Induced Itching: A Butyric Acid Derivative with Potential for Uremic Pruritus." Journal of Clinical Medicine 9, no. 2: 312.
Methicillin-resistant Staphylococcus aureus (S. aureus) (MRSA) has become an alarming threat to public health, and infected soft tissue. Antibiotics are commonly used to treat skin infection with MRSA, but the inappropriate use of antibiotics runs a considerable risk of generating resistant S. aureus. In this study, we created a cysteine-capped hydrogel able to absorb and release copper, an ion with the capability of suppressing the growth of USA300, a community-acquired MRSA. The results of analysis of Fourier transform infrared spectroscopy (FTIR) revealed the binding of copper to a cysteine-capped hydrogel. The topical application of a cysteine-capped hydrogel binding with copper on USA300-infected skin wounds in the dorsal skin of Institute of Cancer Research (ICR) mice significantly enhanced wound healing, hindered the growth of USA300, and reduced the production of pro-inflammatory macrophage inflammatory protein 2-alpha (MIP-2) cytokine. Our work demonstrates a newly designed hydrogel that conjugates a cysteine molecule for copper binding. The cysteine-capped hydrogel can potentially chelate various antimicrobial metals as a novel wound dressing.
John Jackson Yang; Yung-Chi Huang; Tsung-Hsien Chuang; Deron Raymond Herr; Ming-Fa Hsieh. Cysteine-Capped Hydrogels Incorporating Copper as Effective Antimicrobial Materials against Methicillin-Resistant Staphylococcus aureus. Microorganisms 2020, 8, 149 .
AMA StyleJohn Jackson Yang, Yung-Chi Huang, Tsung-Hsien Chuang, Deron Raymond Herr, Ming-Fa Hsieh. Cysteine-Capped Hydrogels Incorporating Copper as Effective Antimicrobial Materials against Methicillin-Resistant Staphylococcus aureus. Microorganisms. 2020; 8 (2):149.
Chicago/Turabian StyleJohn Jackson Yang; Yung-Chi Huang; Tsung-Hsien Chuang; Deron Raymond Herr; Ming-Fa Hsieh. 2020. "Cysteine-Capped Hydrogels Incorporating Copper as Effective Antimicrobial Materials against Methicillin-Resistant Staphylococcus aureus." Microorganisms 8, no. 2: 149.
Ototoxicity is a major adverse effect of platinum-based chemotherapeutics and currently, there remains a lack of United States Food and Drug Administration-approved therapies to prevent or treat this problem. In our study, we examined the role of the sphingosine 1-phosphate receptor 2 (S1P2) in attenuating cisplatin-induced ototoxicity in several different animal models and cell lines. We found that ototoxicity in S1P2 knockout mice is dependent on reactive oxygen species (ROS) production and that S1P2 receptor activation with a specific agonist, CYM-5478, significantly attenuates cisplatin-induced defects, including hair cell degeneration in zebrafish and prolonged auditory brainstem response latency in rats. We also evaluated the cytoprotective effect of CYM-5478 across different cell lines and showed that CYM-5478 protects neural-derived cell lines but not breast cancer cells against cisplatin toxicity. We show that this selective protection of CYM-5478 is due to its differential effects on key regulators of apoptosis between neural cells and breast cancer cells. Overall, our study suggests that targeting the S1P2 receptor represents a promising therapeutic approach for the treatment of cisplatin-induced ototoxicity in cancer patients.
Wei Wang; Muthu K. Shanmugam; Ping Xiang; Ting Yu Amelia Yam; Vineet Kumar; Wee Siong Chew; Jing Kai Chang; Muhammad Zulfaqar Bin Ali; Marie J. Y. Reolo; Yee Xin Peh; Siti Nasuha Binte Abdul Karim; Andrew Y.Y. Tan; Takaomi Sanda; Gautam Sethi; Deron R. Herr. Sphingosine 1-Phosphate Receptor 2 Induces Otoprotective Responses to Cisplatin Treatment. Cancers 2020, 12, 211 .
AMA StyleWei Wang, Muthu K. Shanmugam, Ping Xiang, Ting Yu Amelia Yam, Vineet Kumar, Wee Siong Chew, Jing Kai Chang, Muhammad Zulfaqar Bin Ali, Marie J. Y. Reolo, Yee Xin Peh, Siti Nasuha Binte Abdul Karim, Andrew Y.Y. Tan, Takaomi Sanda, Gautam Sethi, Deron R. Herr. Sphingosine 1-Phosphate Receptor 2 Induces Otoprotective Responses to Cisplatin Treatment. Cancers. 2020; 12 (1):211.
Chicago/Turabian StyleWei Wang; Muthu K. Shanmugam; Ping Xiang; Ting Yu Amelia Yam; Vineet Kumar; Wee Siong Chew; Jing Kai Chang; Muhammad Zulfaqar Bin Ali; Marie J. Y. Reolo; Yee Xin Peh; Siti Nasuha Binte Abdul Karim; Andrew Y.Y. Tan; Takaomi Sanda; Gautam Sethi; Deron R. Herr. 2020. "Sphingosine 1-Phosphate Receptor 2 Induces Otoprotective Responses to Cisplatin Treatment." Cancers 12, no. 1: 211.
Platinum-based therapeutics are used to manage many forms of cancer, but frequently result in peripheral neuropathy. Currently, the only option available to attenuate chemotherapy-induced neuropathy is to limit or discontinue this treatment. Sphingosine 1-phosphate (S1P) is a lipid-based signaling molecule involved in neuroinflammatory processes by interacting with its five cognate receptors: S1P1–5. In this study, using a combination of drug pharmacodynamic analysis in human study participants, disease modeling in rodents, and cell-based assays, we examined whether S1P signaling may represent a potential target in the treatment of chemotherapy-induced neuropathy. To this end, we first investigated the effects of platinum-based drugs on plasma S1P levels in human cancer patients. Our analysis revealed that oxaliplatin treatment specifically increases one S1P species, d16:1 S1P, in these patients. Although d16:1 S1P is an S1P2 agonist, it has lower potency than the most abundant S1P species (d18:1 S1P). Therefore, as d16:1 S1P concentration increases, it is likely to disproportionately activate proinflammatory S1P1 signaling, shifting the balance away from S1P2. We further show that a selective S1P2 agonist, CYM-5478, reduces allodynia in a rat model of cisplatin-induced neuropathy and attenuates the associated inflammatory processes in the dorsal root ganglia, likely by activating stress-response proteins, including ATF3 and HO-1. Cumulatively, the findings of our study suggest that the development of a specific S1P2 agonist may represent a promising therapeutic approach for the management of chemotherapy-induced neuropathy.
Wei Wang; Ping Xiang; Wee Siong Chew; Federico Torta; Aishwarya Bandla; Violeta Lopez; Wei Lun Seow; Brenda Wan Shing Lam; Jing Kai Chang; Peiyan Wong; Kanokporn Chayaburakul; Wei-Yi Ong; Markus R. Wenk; Raghav Sundar; Deron R. Herr. Activation of sphingosine 1-phosphate receptor 2 attenuates chemotherapy-induced neuropathy. Journal of Biological Chemistry 2020, 295, 1143 -1152.
AMA StyleWei Wang, Ping Xiang, Wee Siong Chew, Federico Torta, Aishwarya Bandla, Violeta Lopez, Wei Lun Seow, Brenda Wan Shing Lam, Jing Kai Chang, Peiyan Wong, Kanokporn Chayaburakul, Wei-Yi Ong, Markus R. Wenk, Raghav Sundar, Deron R. Herr. Activation of sphingosine 1-phosphate receptor 2 attenuates chemotherapy-induced neuropathy. Journal of Biological Chemistry. 2020; 295 (4):1143-1152.
Chicago/Turabian StyleWei Wang; Ping Xiang; Wee Siong Chew; Federico Torta; Aishwarya Bandla; Violeta Lopez; Wei Lun Seow; Brenda Wan Shing Lam; Jing Kai Chang; Peiyan Wong; Kanokporn Chayaburakul; Wei-Yi Ong; Markus R. Wenk; Raghav Sundar; Deron R. Herr. 2020. "Activation of sphingosine 1-phosphate receptor 2 attenuates chemotherapy-induced neuropathy." Journal of Biological Chemistry 295, no. 4: 1143-1152.
Microglial cells are resident macrophages of the central nervous system (CNS) that respond to bioactive lipids such as docosahexaenoic acid (DHA). Low micromolar concentrations of DHA typically promote anti-inflammatory functions of microglia, but higher concentrations result in a form of pro-inflammatory programmed cell death known as pyroptosis. This study used scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to investigate the morphological characteristics of pyroptosis in BV-2 microglial cells following exposure to 200 µM DHA. Vehicle-treated cells are characterized by extended processes, spine-like projections or 0.4 to 5.2 µm in length, and numerous extracellular vesicles (EVs) tethered to the surface of the plasma membrane. In contrast to vehicle-treated cells, gross abnormalities are observed after treating cells with 200 µM DHA for 4 h. These include the appearance of numerous pits or pores of varying sizes across the cell surface, structural collapse and flattening of the cell shape. Moreover, EVs and spines were lost following DHA treatment, possibly due to release from the cell surface. The membrane pores appear after DHA treatment initially measured ~ 30 nm, consistent with the previously reported gasdermin D (GSDMD) pore complexes. Complete collapse of cytoplasmic organization and loss of nuclear envelope integrity were also observed in DHA-treated cells. These processes are morphologically distinct from the changes that occur during cisplatin-induced apoptosis, such as the appearance of apoptotic bodies and tightly packed organelles, and the maintenance of EVs and nuclear envelope integrity. Cumulatively, this study provides a systematic description of the ultrastructural characteristics of DHA-induced pyroptosis, including distinguishing features that differentiate this process from apoptosis.
Deron R. Herr; Ting Yu Amelia Yam; Wan Shun Daniel Tan; Sally Shuxian Koh; Wai Shiu Fred Wong; Wei-Yi Ong; Kanokporn Chayaburakul. Ultrastructural Characteristics of DHA-Induced Pyroptosis. NeuroMolecular Medicine 2020, 22, 293 -303.
AMA StyleDeron R. Herr, Ting Yu Amelia Yam, Wan Shun Daniel Tan, Sally Shuxian Koh, Wai Shiu Fred Wong, Wei-Yi Ong, Kanokporn Chayaburakul. Ultrastructural Characteristics of DHA-Induced Pyroptosis. NeuroMolecular Medicine. 2020; 22 (2):293-303.
Chicago/Turabian StyleDeron R. Herr; Ting Yu Amelia Yam; Wan Shun Daniel Tan; Sally Shuxian Koh; Wai Shiu Fred Wong; Wei-Yi Ong; Kanokporn Chayaburakul. 2020. "Ultrastructural Characteristics of DHA-Induced Pyroptosis." NeuroMolecular Medicine 22, no. 2: 293-303.
Platinum-based therapeutics are used to manage many forms of cancer, but frequently result in peripheral neuropathy. Currently, the only option available to attenuate chemotherapy-induced neuropathy is to limit or discontinue this treatment. Sphingosine 1-phosphate (S1P) is a lipid-based signaling molecule involved in neuroinflammatory processes by interacting with its five cognate receptors: S1P1–5. In this study, using a combination of drug pharmacodynamic analysis in human study participants, disease modeling in rodents, and cell-based assays, we examined whether S1P signaling may represent a potential target in the treatment of chemotherapy-induced neuropathy. To this end, we first investigated the effects of platinum-based drugs on plasma S1P levels in human cancer patients. Our analysis revealed that oxaliplatin treatment specifically increases one S1P species, d16:1 S1P, in these patients. Although d16:1 S1P is an S1P2 agonist, it has lower potency than the most abundant S1P species (d18:1 S1P). Therefore, as d16:1 S1P concentration increases, it is likely to disproportionately activate proinflammatory S1P1 signaling, shifting the balance away from S1P2. We further show that a selective S1P2 agonist, CYM-5478, reduces allodynia in a rat model of cisplatin-induced neuropathy and attenuates the associated inflammatory processes in the dorsal root ganglia, likely by activating stress-response proteins, including ATF3 and HO-1. Cumulatively, the findings of our study suggest that the development of a specific S1P2 agonist may represent a promising therapeutic approach for the management of chemotherapy-induced neuropathy.
Wei Wang; Ping Xiang; Wee Siong Chew; Federico Torta; Aishwarya Bandla; Violeta Lopez; Wei Lun Seow; Brenda Wan Shing Lam; Jing Kai Chang; Peiyan Wong; Kanokporn Chayaburakul; Wei-Yi Ong; Markus R. Wenk; Raghav Sundar; Deron R. Herr. Activation of sphingosine 1-phosphate receptor 2 attenuates chemotherapy-induced neuropathy. Journal of Biological Chemistry 2019, 295, 1143 -1152.
AMA StyleWei Wang, Ping Xiang, Wee Siong Chew, Federico Torta, Aishwarya Bandla, Violeta Lopez, Wei Lun Seow, Brenda Wan Shing Lam, Jing Kai Chang, Peiyan Wong, Kanokporn Chayaburakul, Wei-Yi Ong, Markus R. Wenk, Raghav Sundar, Deron R. Herr. Activation of sphingosine 1-phosphate receptor 2 attenuates chemotherapy-induced neuropathy. Journal of Biological Chemistry. 2019; 295 (4):1143-1152.
Chicago/Turabian StyleWei Wang; Ping Xiang; Wee Siong Chew; Federico Torta; Aishwarya Bandla; Violeta Lopez; Wei Lun Seow; Brenda Wan Shing Lam; Jing Kai Chang; Peiyan Wong; Kanokporn Chayaburakul; Wei-Yi Ong; Markus R. Wenk; Raghav Sundar; Deron R. Herr. 2019. "Activation of sphingosine 1-phosphate receptor 2 attenuates chemotherapy-induced neuropathy." Journal of Biological Chemistry 295, no. 4: 1143-1152.
Metabolites are small intermediate products of cellular metabolism perturbed in a variety of complex disorders. Identifying genetic markers associated with metabolite concentrations could delineate disease-related metabolic pathways in humans. We tested genetic variants for associations with 136 metabolites in 1,954 Chinese from Singapore. At a conservative genome-wide threshold (3.7 x 10-10), we detected 1,899 variant-metabolite associations at 16 genetic loci. Three loci (ABCA7, A4GALT, GSTM2) represented novel associations with metabolites, with the strongest association observed between ABCA7 and d18:1/24:1 dihexosylceramide. Among 13 replicated loci, we identified six new variants independent of previously reported metabolite or lipid signals. We observed variant-metabolite associations at two loci (ABCA7, CHCHD2) that have been linked to neurodegenerative diseases. At SGPP1 and SPTLC3 loci, genetic variants showed preferential selectivity for sphingolipids with d16 (rather than d18) sphingosine backbone, including sphingosine-1-phosphate (S1P). Our results provide new genetic associations for metabolites and highlight the role of metabolites as intermediate modulators in disease metabolic pathways.
Jin-Fang Chai; Suryaprakash Raichur; Ing Wei Khor; Federico Torta; Wee Siong Chew; Deron Herr; Jian-Hong Ching; Jean Paul Kovalik; Chin Meng Khoo; Markus R Wenk; E Shyong Tai; Xueling Sim. Associations with metabolites in Chinese suggest new metabolic roles in Alzheimer's and Parkinson's diseases. Human Molecular Genetics 2019, 1 .
AMA StyleJin-Fang Chai, Suryaprakash Raichur, Ing Wei Khor, Federico Torta, Wee Siong Chew, Deron Herr, Jian-Hong Ching, Jean Paul Kovalik, Chin Meng Khoo, Markus R Wenk, E Shyong Tai, Xueling Sim. Associations with metabolites in Chinese suggest new metabolic roles in Alzheimer's and Parkinson's diseases. Human Molecular Genetics. 2019; ():1.
Chicago/Turabian StyleJin-Fang Chai; Suryaprakash Raichur; Ing Wei Khor; Federico Torta; Wee Siong Chew; Deron Herr; Jian-Hong Ching; Jean Paul Kovalik; Chin Meng Khoo; Markus R Wenk; E Shyong Tai; Xueling Sim. 2019. "Associations with metabolites in Chinese suggest new metabolic roles in Alzheimer's and Parkinson's diseases." Human Molecular Genetics , no. : 1.
Human A3 adenosine receptor hA3AR has been implicated in gastrointestinal cancer, where its cellular expression has been found increased, thus suggesting its potential as a molecular target for novel anticancer compounds. Observation made in our previous work indicated the importance of the carbonyl group of amide in the indolylpyrimidylpiperazine (IPP) for its human A2A adenosine receptor (hA2AAR) subtype binding selectivity over the other AR subtypes. Taking this observation into account, we structurally modified an indolylpyrimidylpiperazine (IPP) scaffold, 1 (a non-selective adenosine receptors' ligand) into a modified IPP (mIPP) scaffold by switching the position of the carbonyl group, resulting in the formation of both ketone and tertiary amine groups in the new scaffold. Results showed that such modification diminished the A2A activity and instead conferred hA3AR agonistic activity. Among the new mIPP derivatives (3-6), compound 4 showed potential as a hA3AR partial agonist, with an Emax of 30% and EC50 of 2.89 ± 0.55 μM. In the cytotoxicity assays, compound 4 also exhibited higher cytotoxicity against both colorectal and liver cancer cells as compared to normal cells. Overall, this new series of compounds provide a promising starting point for further development of potent and selective hA3AR partial agonists for the treatment of gastrointestinal cancers.
Aaron Tan; Maria V. Babak; Gopalakrishnan Venkatesan; Clarissa Lim; Karl-Norbert Klotz; Deron Raymond Herr; Siew Lee Cheong; Stephanie Federico; Giampiero Spalluto; Wei-Yi Ong; Yu Zong Chen; Jason Siau Ee Loo; Giorgia Pastorin. Design, Synthesis and Evaluation of New Indolylpyrimidylpiperazines for Gastrointestinal Cancer Therapy. Molecules 2019, 24, 3661 .
AMA StyleAaron Tan, Maria V. Babak, Gopalakrishnan Venkatesan, Clarissa Lim, Karl-Norbert Klotz, Deron Raymond Herr, Siew Lee Cheong, Stephanie Federico, Giampiero Spalluto, Wei-Yi Ong, Yu Zong Chen, Jason Siau Ee Loo, Giorgia Pastorin. Design, Synthesis and Evaluation of New Indolylpyrimidylpiperazines for Gastrointestinal Cancer Therapy. Molecules. 2019; 24 (20):3661.
Chicago/Turabian StyleAaron Tan; Maria V. Babak; Gopalakrishnan Venkatesan; Clarissa Lim; Karl-Norbert Klotz; Deron Raymond Herr; Siew Lee Cheong; Stephanie Federico; Giampiero Spalluto; Wei-Yi Ong; Yu Zong Chen; Jason Siau Ee Loo; Giorgia Pastorin. 2019. "Design, Synthesis and Evaluation of New Indolylpyrimidylpiperazines for Gastrointestinal Cancer Therapy." Molecules 24, no. 20: 3661.
The glycerol fermentation of probiotic Staphylococcus epidermidis (S. epidermidis) in the skin microbiome produced butyric acid in vitro at concentrations in the millimolar range. The exposure of dorsal skin of mice to ultraviolet B (UVB) light provoked a significant increased production of pro-inflammatory interleukin (IL)-6 cytokine. Topical application of butyric acid alone or S. epidermidis with glycerol remarkably ameliorated the UVB-induced IL-6 production. In vivo knockdown of short-chain fatty acid receptor 2 (FFAR2) in mouse skin considerably blocked the probiotic effect of S. epidermidis on suppression of UVB-induced IL-6 production. These results demonstrate that butyric acid in the metabolites of fermenting skin probiotic bacteria mediates FFAR2 to modulate the production of pro-inflammatory cytokines induced by UVB.
Sunita Keshari; Arun Balasubramaniam; Binderiya Myagmardoloonjin; Deron Raymond Herr; Indira Putri Negari; Chun-Ming Huang. Butyric Acid from Probiotic Staphylococcus epidermidis in the Skin Microbiome Down-Regulates the Ultraviolet-Induced Pro-Inflammatory IL-6 Cytokine via Short-Chain Fatty Acid Receptor. International Journal of Molecular Sciences 2019, 20, 4477 .
AMA StyleSunita Keshari, Arun Balasubramaniam, Binderiya Myagmardoloonjin, Deron Raymond Herr, Indira Putri Negari, Chun-Ming Huang. Butyric Acid from Probiotic Staphylococcus epidermidis in the Skin Microbiome Down-Regulates the Ultraviolet-Induced Pro-Inflammatory IL-6 Cytokine via Short-Chain Fatty Acid Receptor. International Journal of Molecular Sciences. 2019; 20 (18):4477.
Chicago/Turabian StyleSunita Keshari; Arun Balasubramaniam; Binderiya Myagmardoloonjin; Deron Raymond Herr; Indira Putri Negari; Chun-Ming Huang. 2019. "Butyric Acid from Probiotic Staphylococcus epidermidis in the Skin Microbiome Down-Regulates the Ultraviolet-Induced Pro-Inflammatory IL-6 Cytokine via Short-Chain Fatty Acid Receptor." International Journal of Molecular Sciences 20, no. 18: 4477.
Autotaxin (ATX) is a soluble extracellular enzyme that is abundant in mammalian plasma and cerebrospinal fluid (CSF). It has two known enzymatic activities, acting as both a phosphodiesterase and a phospholipase. The majority of its biological effects have been associated with its ability to liberate lysophosphatidic acid (LPA) from its substrate, lysophosphatidylcholine (LPC). LPA has diverse pleiotropic effects in the central nervous system (CNS) and other tissues via the activation of a family of six cognate G protein-coupled receptors. These LPA receptors (LPARs) are expressed in some combination in all known cell types in the CNS where they mediate such fundamental cellular processes as proliferation, differentiation, migration, chronic inflammation, and cytoskeletal organization. As a result, dysregulation of LPA content may contribute to many CNS and PNS disorders such as chronic inflammatory or neuropathic pain, glioblastoma multiforme (GBM), hemorrhagic hydrocephalus, schizophrenia, multiple sclerosis, Alzheimer's disease, metabolic syndrome-induced brain damage, traumatic brain injury, hepatic encephalopathy-induced cerebral edema, macular edema, major depressive disorder, stress-induced psychiatric disorder, alcohol-induced brain damage, HIV-induced brain injury, pruritus, and peripheral nerve injury. ATX activity is now known to be the primary biological source of this bioactive signaling lipid, and as such, represents a potentially high-value drug target. There is currently one ATX inhibitor entering phase III clinical trials, with several additional preclinical compounds under investigation. This review discusses the physiological and pathological significance of the ATX-LPA-LPA receptor signaling axis and summarizes the evidence for targeting this pathway for the treatment of CNS diseases.
Deron R. Herr; Wee Siong Chew; R. L. Satish; Wei-Yi Ong. Pleotropic Roles of Autotaxin in the Nervous System Present Opportunities for the Development of Novel Therapeutics for Neurological Diseases. Molecular Neurobiology 2019, 57, 372 -392.
AMA StyleDeron R. Herr, Wee Siong Chew, R. L. Satish, Wei-Yi Ong. Pleotropic Roles of Autotaxin in the Nervous System Present Opportunities for the Development of Novel Therapeutics for Neurological Diseases. Molecular Neurobiology. 2019; 57 (1):372-392.
Chicago/Turabian StyleDeron R. Herr; Wee Siong Chew; R. L. Satish; Wei-Yi Ong. 2019. "Pleotropic Roles of Autotaxin in the Nervous System Present Opportunities for the Development of Novel Therapeutics for Neurological Diseases." Molecular Neurobiology 57, no. 1: 372-392.
Sphingolipids (SPs) are ubiquitous, structurally diverse molecules that include ceramides, sphingomyelins (SMs), and sphingosines. They are involved in various pathologies, including obesity and type 2 diabetes mellitus (T2DM). Therefore, it is likely that perturbations in plasma concentrations of SPs are associated with disease. Identifying these associations may reveal useful biomarkers or provide insight into disease processes. We performed a lipidomics evaluation of molecularly distinct SPs in the plasma of 2302 ethnically Chinese Singaporeans using electrospray ionization mass spectrometry coupled with liquid chromatography. SP profiles were compared to clinical and biochemical characteristics, and subjects were evaluated with follow-up visits for 11 years. We found that ceramides correlated positively but hexosylceramides correlated negatively with BMI and homeostatic model assessment of insulin resistance (HOMA-IR). Furthermore, SPs with a d16:1 sphingoid backbone correlated more positively with BMI and HOMA-IR, while d18:2 SPs correlated less positively, relative to canonical d18:1 SPs. We also found that higher concentrations of 2 distinct SMs were associated with a higher risk of T2DM (HR 1.45 with 95% CI 1.18–1.78 for SM d16:1/18:0 and HR 1.40 with 95% CI 1.17–1.68 for SM d18:1/18:0). We identified significant associations between SPs and obesity/T2DM characteristics, specifically, those of hexosylceramides, d16:1 SPs, and d18:2 SPs. This suggests that the balance of SP metabolism, rather than ceramide accumulation, is associated with the pathology of obesity. We further identified 2 specific SPs that may represent prognostic biomarkers for T2DM. National University Health System (NUHSRO/2014/085/AF-Partner/01) and the National Research Foundation Investigatorship grant (NRF-NRFI2015-05).
Wee Siong Chew; Federico Torta; Shanshan Ji; Hyungwon Choi; Husna Begum; Xueling Sim; Chin Meng Khoo; Eric Yin Hao Khoo; Wei-Yi Ong; Rob M. Van Dam; Markus R. Wenk; E. Shyong Tai; Deron R. Herr. Large-scale lipidomics identifies associations between plasma sphingolipids and T2DM incidence. JCI Insight 2019, 4, 1 .
AMA StyleWee Siong Chew, Federico Torta, Shanshan Ji, Hyungwon Choi, Husna Begum, Xueling Sim, Chin Meng Khoo, Eric Yin Hao Khoo, Wei-Yi Ong, Rob M. Van Dam, Markus R. Wenk, E. Shyong Tai, Deron R. Herr. Large-scale lipidomics identifies associations between plasma sphingolipids and T2DM incidence. JCI Insight. 2019; 4 (13):1.
Chicago/Turabian StyleWee Siong Chew; Federico Torta; Shanshan Ji; Hyungwon Choi; Husna Begum; Xueling Sim; Chin Meng Khoo; Eric Yin Hao Khoo; Wei-Yi Ong; Rob M. Van Dam; Markus R. Wenk; E. Shyong Tai; Deron R. Herr. 2019. "Large-scale lipidomics identifies associations between plasma sphingolipids and T2DM incidence." JCI Insight 4, no. 13: 1.