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Article: Significant association of elevated serum galectin-9 levels with the development of non-alcoholic fatty liver disease in patients with rheumatoid arthritis.

Chen, Po-Ku / Hsu, Wei-Fan / Peng, Cheng-Yuan / Liao, Tsai-Ling / Chang, Shih-Hsin / Chen, Hsin-Hua / Chen, Chu-Huang / Chen, Der-Yuan

Frontiers in medicine

2024 Volume 11, Page(s) 1347268

Abstract: Background: Non-alcoholic fatty liver disease (NAFLD) is prevalent among rheumatoid arthritis (RA) patients, but its pathogenesis has rarely been explored. Galectin-9 (Gal-9) interacts with T cell immunoglobulin and mucin-containing-molecule-3 (TIM-3) ... ...

Abstract	Background: Non-alcoholic fatty liver disease (NAFLD) is prevalent among rheumatoid arthritis (RA) patients, but its pathogenesis has rarely been explored. Galectin-9 (Gal-9) interacts with T cell immunoglobulin and mucin-containing-molecule-3 (TIM-3) expressed on hepatocytes and thus regulates T cell proliferation in a murine model of NAFLD. We aimed to examine the pathogenic role of the Gal-9/TIM-3 pathway in RA-NAFLD. Methods: Serum levels of Gal-9, soluble TIM-3 (sTIM-3), fatty acid-binding proteins (FABP)1, and FABP4 were determined by ELISA in forty-five RA patients and eleven healthy participants. Using Oil-red O staining and immunoblotting, we examined the effects of Gal-9 and free fatty acid (FFA) on lipid accumulation in human hepatocytes and FABP1 expression. Results: Serum Gal-9, sTIM-3 and FABP1 level were significantly higher in RA patients (median 5.02 ng/mL, 3.42 ng/mL, and 5.76 ng/mL, respectively) than in healthy participants (1.86 ng/mL, 0.99 ng/mL, and 0.129 ng/mL, all Conclusion: Elevated levels of Gal-9 and sTIM3 in RA patients with NAFLD and their positive correlation with NAFLD severity suggest the pathogenic role of Gal-9 signaling in RA-related NAFLD.
Language	English
Publishing date	2024-02-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2024.1347268
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Article ; Online: Influence of electromagnetic fields on the circadian rhythm: Implications for human health and disease.

Martel, Jan / Chang, Shih-Hsin / Chevalier, Gaétan / Ojcius, David M / Young, John D

Biomedical journal

2023 Volume 46, Issue 1, Page(s) 48–59

Abstract: Living organisms have evolved within the natural electromagnetic fields (EMFs) of the earth which comprise the global atmospheric electrical circuit, Schumann resonances (SRs) and the geomagnetic field. Research suggests that the circadian rhythm, which ... ...

Abstract	Living organisms have evolved within the natural electromagnetic fields (EMFs) of the earth which comprise the global atmospheric electrical circuit, Schumann resonances (SRs) and the geomagnetic field. Research suggests that the circadian rhythm, which controls several physiological functions in the human body, can be influenced by light but also by the earth's EMFs. Cyclic solar disturbances, including sunspots and seasonal weakening of the geomagnetic field, can affect human health, possibly by disrupting the circadian rhythm and downstream physiological functions. Severe disruption of the circadian rhythm increases inflammation which can induce fatigue, fever and flu-like symptoms in a fraction of the population and worsen existing symptoms in old and diseased individuals, leading to periodic spikes of infectious and chronic diseases. Possible mechanisms underlying sensing of the earth's EMFs involve entrainment via electrons and electromagnetic waves, light-dependent radical pair formation in retina cryptochromes, and paramagnetic magnetite nanoparticles. Factors such as electromagnetic pollution from wireless devices, base antennas and low orbit internet satellites, shielding by non-conductive materials used in shoes and buildings, and local geomagnetic anomalies may also affect sensing of the earth's EMFs by the human body and contribute to circadian rhythm disruption and disease development.
MeSH term(s)	Humans ; Electromagnetic Fields/adverse effects ; Circadian Rhythm
Language	English
Publishing date	2023-01-19
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2698541-X
ISSN	2320-2890 ; 2320-2890
ISSN (online)	2320-2890
ISSN	2320-2890
DOI	10.1016/j.bj.2023.01.003
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Article ; Online: MicroRNAs mediate precise control of spinal interneuron populations to exert delicate sensory-to-motor outputs.

Chang, Shih-Hsin / Su, Yi-Ching / Chang, Mien / Chen, Jun-An

eLife

2021 Volume 10

Abstract: Although the function of microRNAs (miRNAs) during embryonic development has been intensively studied in recent years, their postnatal physiological functions remain largely unexplored due to inherent difficulties with the presence of redundant paralogs ... ...

Abstract	Although the function of microRNAs (miRNAs) during embryonic development has been intensively studied in recent years, their postnatal physiological functions remain largely unexplored due to inherent difficulties with the presence of redundant paralogs of the same seed. Thus, it is particularly challenging to uncover miRNA functions at neural circuit level since animal behaviors would need to be assessed upon complete loss of miRNA family functions. Here, we focused on the neural functions of MiR34/449 that manifests a dynamic expression pattern in the spinal cord from embryonic to postnatal stages. Our behavioral assays reveal that the loss of MiR34/449 miRNAs perturb thermally induced pain response thresholds and compromised delicate motor output in mice. Mechanistically, MiR34/449 directly target
MeSH term(s)	Animals ; Female ; Interneurons/metabolism ; Male ; Mice ; Mice, Knockout ; MicroRNAs/metabolism ; Motor Neurons/metabolism ; Spine/metabolism
Chemical Substances	MicroRNAs
Language	English
Publishing date	2021-03-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.63768
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Article: High-titer anti-interferon-γ neutralizing autoantibodies linked to opportunistic infections in patients with adult-onset still's disease.

Chen, Po-Ku / Liao, Tsai-Ling / Chang, Shih-Hsin / Yeo, Kai-Jieh / Chou, Chia-Hui / Chen, Der-Yuan

Frontiers in medicine

2023 Volume 9, Page(s) 1097514

Abstract: Objective: Neutralizing anti-interferon (IFN)-γ autoantibodies are linked to opportunistic infections (OIs). To explore the association between anti-IFN-γ autoantibodies and OIs in patients with adult-onset Still's disease (AOSD), we aimed to examine ... ...

Abstract	Objective: Neutralizing anti-interferon (IFN)-γ autoantibodies are linked to opportunistic infections (OIs). To explore the association between anti-IFN-γ autoantibodies and OIs in patients with adult-onset Still's disease (AOSD), we aimed to examine the ability of these autoantibodies to blockade signal transducer and activator of transcription (STAT1)-phosphorylation and chemokines production. Methods: Serum titers of anti-IFN-γ autoantibodies were quantified using ELISA in 29 AOSD and 22 healthy controls (HC). The detectable autoantibodies were verified with immunoblotting assay, and their neutralizing capacity against IFN-γ-signaling was evaluated with flow-cytometry analysis and immunoblotting. IFN-γ-mediated production of supernatant chemokines, including monocyte chemoattractant protein-1 (MCP-1) and IFN-γ inducible protein-10 (IP-10), were measured by ELISA. Results: Among 29 AOSD patients, high titers of anti-IFN-γ neutralizing autoantibodies were detectable in two patients with OIs. Immunoblotting assay revealed more effective inhibition of STAT1-phosphorylation in THP-1 cells treated with sera from autoantibody-positive AOSD patients (56.7 ± 34.79%) compared with those from HC (104.3 ±29.51%), which was also demonstrated in flow-cytometry analysis (47.13 ± 40.99 vs. 97.92 ± 9.48%, Conclusion: AOSD patients have a high positive rate and titers of anti-IFN-γ autoantibodies. The remarkable blockade effect of high-titer autoantibodies on IFN-γ-mediated STAT1-phosphorylation and chemokines could make these patients susceptible to OIs.
Language	English
Publishing date	2023-01-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2022.1097514
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Article ; Online: The detectable anti-interferon-γ autoantibodies in COVID-19 patients may be associated with disease severity.

Chen, Po-Ku / Yeo, Kai-Jieh / Chang, Shih-Hsin / Liao, Tsai-Ling / Chou, Chia-Hui / Lan, Joung-Liang / Chang, Ching-Kun / Chen, Der-Yuan

Virology journal

2023 Volume 20, Issue 1, Page(s) 33

Abstract: Background: Neutralizing anti-interferon (IFN)-γ autoantibodies are linked to adult-onset immunodeficiency and opportunistic infections.: Methods: To explore whether anti-IFN-γ autoantibodies are associated with disease severity of coronavirus ... ...

Abstract	Background: Neutralizing anti-interferon (IFN)-γ autoantibodies are linked to adult-onset immunodeficiency and opportunistic infections. Methods: To explore whether anti-IFN-γ autoantibodies are associated with disease severity of coronavirus disease 2019 (COVID-19), we examined the titers and functional neutralization of anti-IFN-γ autoantibodies in COVID-19 patients. In 127 COVID-19 patients and 22 healthy controls, serum titers of anti-IFN-γ autoantibodies were quantified using enzyme-linked immunosorbent assay, and the presence of autoantibodies was verified with immunoblotting assay. The neutralizing capacity against IFN-γ was evaluated with flow cytometry analysis and immunoblotting, and serum cytokines levels were determined using the MULTIPLEX platform. Results: A higher proportion of severe/critical COVID-19 patients had positivity for anti-IFN-γ autoantibodies (18.0%) compared with non-severe patients (3.4%, p < 0.01) or healthy control (HC) (0.0%, p < 0.05). Severe/critical COVID-19 patients also had higher median titers of anti-IFN-γ autoantibodies (5.01) compared with non-severe patients (1.33) or HC (0.44). The immunoblotting assay could verify the detectable anti-IFN-γ autoantibodies and revealed more effective inhibition of signal transducer and activator of transcription (STAT1) phosphorylation on THP-1 cells treated with serum samples from anti-IFN-γ autoantibodies-positive patients compared with those from HC (2.21 ± 0.33 versus 4.47 ± 1.64, p < 0.05). In flow-cytometry analysis, sera from autoantibodies-positive patients could also significantly more effectively suppress the STAT1 phosphorylation (median,67.28%, interquartile range [IQR] 55.2-78.0%) compared with serum from HC (median,106.7%, IQR 100.0-117.8%, p < 0.05) or autoantibodies-negative patients (median,105.9%, IQR 85.5-116.3%, p < 0.05). Multivariate analysis revealed that the positivity and titers of anti-IFN-γ autoantibodies were significant predictors of severe/critical COVID-19. Compared with non-severe COVID-19 patients, we reveal that a significantly higher proportion of severe/critical COVID-19 patients are positive for anti-IFN-γ autoantibodies with neutralizing capacity. Conclusion: Our results would add COVID-19 to the list of diseases with the presence of neutralizing anti-IFN-γ autoAbs. Anti-IFN-γ autoantibodies positivity is a potential predictor of severe/critical COVID-19.
MeSH term(s)	Adult ; Humans ; Autoantibodies ; COVID-19 ; Interferon-gamma ; Cytokines ; Patient Acuity
Chemical Substances	Autoantibodies ; Interferon-gamma (82115-62-6) ; Cytokines
Language	English
Publishing date	2023-02-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2160640-7
ISSN	1743-422X ; 1743-422X
ISSN (online)	1743-422X
ISSN	1743-422X
DOI	10.1186/s12985-023-01989-1
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Article ; Online: Immune cell profiles of idiopathic inflammatory myopathy patients expressed anti-aminoacyl tRNA synthetase or anti-melanoma differentiation-associated gene 5 autoantibodies.

Lan, Joung-Liang / Chang, Shih-Hsin / Tsay, Gregory J / Chen, Der-Yuan / Chao, Yu-Hua / Li, Ju-Pi

BMC immunology

2023 Volume 24, Issue 1, Page(s) 33

Abstract: Background: Patients with idiopathic inflammatory myopathy (IIM) often express a different type of myositis-specific autoantibodies (MSAs), each associated with different clinical symptoms. Understanding the immunopathogenesis of various IIM subgroups ... ...

Abstract	Background: Patients with idiopathic inflammatory myopathy (IIM) often express a different type of myositis-specific autoantibodies (MSAs), each associated with different clinical symptoms. Understanding the immunopathogenesis of various IIM subgroups can help improve the diagnosis and prognosis of IIM patients with different MSAs. However, the immune cell profiles of these IIM patients with anti-aminoacyl tRNA synthetase (ARS) or anti-melanoma differentiation-associated gene 5 (MDA5) autoantibodies remain unclear. We focused on the immune cell profiles of IIM patients with anti-ARS or anti-MDA5 autoantibodies. Results: The peripheral blood from IIM patients with anti-MDA5 autoantibody (MDA5 + group, n = 24) or one of the anti-ARS autoantibodies (ARS + group, n = 40) autoantibodies, and healthy controls (HC group, n = 60) were collected and examined. We found that IIM patients had a lower CD3 T cell population compared to the HC group. IIM patients showed a significantly lower T Conclusions: Our study demonstrated that elevated Th1 may be a good prognostic indicator in IIM patients with ARS + or MDA5 + . Elevated Treg may also help predict a good prognosis in MDA5 + IIM patients. However, more large-scale studies and clinical samples are needed to verify the significance of Th1 and Treg cell subsets in clinical outcomes for these IIM patients with ARS + or MDA5 + . These data may help design a therapeutic approach that specifically targets the pathogenic immune molecular responsible for autoimmune attacks in IIM.
MeSH term(s)	Humans ; Autoantibodies ; Amino Acyl-tRNA Synthetases ; Myositis/diagnosis ; Prognosis ; Cell Differentiation ; Retrospective Studies
Chemical Substances	Autoantibodies ; Amino Acyl-tRNA Synthetases (EC 6.1.1.-)
Language	English
Publishing date	2023-09-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2041500-X
ISSN	1471-2172 ; 1471-2172
ISSN (online)	1471-2172
ISSN	1471-2172
DOI	10.1186/s12865-023-00569-w
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Article: Elevated monocyte distribution width in patients with active adult-onset Still's disease: a novel activity indicator.

Lin, Yun-Hsien / Chang, Shih-Hsin / Hsu, Teng-Chieh / Chen, Po-Ku / Lan, Joung-Liang / Chen, Der-Yuan

Clinical and experimental rheumatology

2023 Volume 41, Issue 10, Page(s) 2062–2070

Abstract: Objectives: Monocyte distribution width (MDW) correlates with volume modifications of circulating monocytes upon activation. Given the crucial role of monocyte activation in the pathogenesis of adult-onset Still's disease (AOSD), we aimed to examine the ...

Abstract	Objectives: Monocyte distribution width (MDW) correlates with volume modifications of circulating monocytes upon activation. Given the crucial role of monocyte activation in the pathogenesis of adult-onset Still's disease (AOSD), we aimed to examine the associations between MDW and disease activity or inflammatory parameters in this disease. Methods: In 58 AOSD patients and 95 other patients with coronavirus disease 2019 (COVID-19) as disease control, MDW and complete blood count were determined using a UniCel DxH800 analyser. C-reactive protein (CRP) levels were measured by nephelometry, and ferritin levels by chemiluminescent immunoassay. AOSD activity was assessed using a modified Pouchot score. Results: MDW was significantly higher in active AOSD patients (median 28.3, interquartile range [IQR] 23.3-32.1) compared with inactive AOSD (19.2, IQR 18.0-20.6, p<0.001) or non-severe COVID-19 patients (23.2, IQR 21.0-25.2, p<0.01). MDW was positively correlated with AOSD activity scores, CRP, and ferritin levels (all p<0.001). Longitudinal follow-up evaluation revealed that median MDW significantly declined (28.3 versus 18.5, p<0.001) along with disease activity, paralleling a decrease in CRP and ferritin levels. Severe COVID-19 and sepsis patients had elevated MDW, which were not different from active AOSD patients. Multivariate analysis revealed MDW as a significant predictor of active AOSD, and MDW threshold at 21.7 could predict an active status with a high sensitivity of 91.3% and specificity of 94.3%. Conclusions: Elevated MDW and its positive correlation with inflammatory parameters in AOSD patients indicate MDW as a novel activity indicator, with a high MDW value above 21.7 linked to a high probability of active AOSD.
MeSH term(s)	Adult ; Humans ; Still's Disease, Adult-Onset ; Monocytes ; Severity of Illness Index ; Ferritins ; COVID-19 ; Biomarkers
Chemical Substances	Ferritins (9007-73-2) ; Biomarkers
Language	English
Publishing date	2023-07-13
Publishing country	Italy
Document type	Journal Article
ZDB-ID	605886-3
ISSN	1593-098X ; 0392-856X
ISSN (online)	1593-098X
ISSN	0392-856X
DOI	10.55563/clinexprheumatol/jbm7pb
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Article ; Online: Increased NAFLD risk in newly diagnosed patients with RA during the first 4 years of follow-up: a nationwide, population-based cohort study.

Ho, Wei-Li / Chen, Hsin-Hua / Chen, Po-Ku / Liao, Tsai-Ling / Chang, Shih-Hsin / Chen, Yi-Ming / Lin, Ching-Heng / Tang, Kuo-Tung / Chen, Der-Yuan

BMJ open

2024 Volume 14, Issue 1, Page(s) e079296

Abstract: Background: Although the non-alcoholic fatty liver disease (NAFLD) is prevalent in the general population, NAFLD risk in newly diagnosed rheumatoid arthritis (RA) has rarely been explored. In this population-based cohort, we examined NAFLD risk in ... ...

Abstract	Background: Although the non-alcoholic fatty liver disease (NAFLD) is prevalent in the general population, NAFLD risk in newly diagnosed rheumatoid arthritis (RA) has rarely been explored. In this population-based cohort, we examined NAFLD risk in patients with RA and identified the potential risk factors. Design: Retrospective study. Setting: Taiwan. Participants: 2281 newly diagnosed patients with RA and selected 91 240 individuals without RA to match with patients with RA (1:40) by age, gender, income status and urbanisation level of the residence. Outcomes: In this retrospective study using the 2000-2018 claim data from two-million representative Taiwanese population, we identified and compared the incidence rates (IRs) of NAFLD and alcoholic fatty liver disease (AFLD) between RA and non-RA groups. Using multivariable regression analyses, we estimated adjusted HR (aHR) of NAFLD development in patients with RA compared with individuals without RA, with 95% CIs. Results: The incidences of NALFD and AFLD were not significantly different between individuals with RA and without RA during the 17-year follow-up period. However, patients with RA had significantly increased NAFLD risk during the first 4 years after RA diagnosis, with IR ratio of 1.66 fold (95% CI 1.18 to 2.33, p<0.005), but the risk was reduced after the first 4 years. Multivariable regression analyses revealed that aHR was 2.77-fold greater in patients not receiving disease-modifying anti-rheumatic drugs therapy than in non-RA subjects (p<0.05). Old age, women, low-income status and obesity could significantly predict NAFLD development. Conclusions: We demonstrated elevated risk of NAFLD in patients with RA during the first 4 years after RA diagnosis, and old age, women, low-income status and obesity were significant predictors of NAFLD.
MeSH term(s)	Humans ; Female ; Non-alcoholic Fatty Liver Disease/complications ; Non-alcoholic Fatty Liver Disease/epidemiology ; Retrospective Studies ; Cohort Studies ; Arthritis, Rheumatoid/complications ; Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/epidemiology ; Risk Factors ; Obesity
Language	English
Publishing date	2024-01-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2023-079296
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Article ; Online: Strongly Improving the Sensitivity of Phosphorescence-Based Optical Oxygen Sensors by Exploiting Nano-Porous Substrates.

Liu, Chih-Yi / Sadhu, Annada Sankar / Karmakar, Riya / Chu, Cheng-Shane / Lin, Yi-Nan / Chang, Shih-Hsin / Dalapati, Goutam Kumar / Biring, Sajal

Biosensors

2022 Volume 12, Issue 10

Abstract: Sensitivity is one of the crucial factors in determining the quality of a fluorescence/phosphorescence-based gas sensor, and is estimated from the measurement of responses ( ... ...

Abstract	Sensitivity is one of the crucial factors in determining the quality of a fluorescence/phosphorescence-based gas sensor, and is estimated from the measurement of responses (I
MeSH term(s)	Porphyrins/chemistry ; Platinum/chemistry ; Oxygen/chemistry ; Porosity ; Aluminum Oxide
Chemical Substances	Porphyrins ; Platinum (49DFR088MY) ; Oxygen (S88TT14065) ; Aluminum Oxide (LMI26O6933)
Language	English
Publishing date	2022-09-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662125-3
ISSN	2079-6374 ; 2079-6374
ISSN (online)	2079-6374
ISSN	2079-6374
DOI	10.3390/bios12100774
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Article ; Online: Gut barrier disruption and chronic disease.

Martel, Jan / Chang, Shih-Hsin / Ko, Yun-Fei / Hwang, Tsong-Long / Young, John D / Ojcius, David M

Trends in endocrinology and metabolism: TEM

2022 Volume 33, Issue 4, Page(s) 247–265

Abstract: The intestinal barrier protects the host against gut microbes, food antigens, and toxins present in the gastrointestinal tract. However, gut barrier integrity can be affected by intrinsic and extrinsic factors, including genetic predisposition, the ... ...

Abstract	The intestinal barrier protects the host against gut microbes, food antigens, and toxins present in the gastrointestinal tract. However, gut barrier integrity can be affected by intrinsic and extrinsic factors, including genetic predisposition, the Western diet, antibiotics, alcohol, circadian rhythm disruption, psychological stress, and aging. Chronic disruption of the gut barrier can lead to translocation of microbial components into the body, producing systemic, low-grade inflammation. While the association between gut barrier integrity and inflammation in intestinal diseases is well established, we review here recent studies indicating that the gut barrier and microbiota dysbiosis may contribute to the development of metabolic, autoimmune, and aging-related disorders. Emerging interventions to improve gut barrier integrity and microbiota composition are also described.
MeSH term(s)	Chronic Disease ; Dysbiosis ; Gastrointestinal Microbiome ; Humans ; Inflammation ; Microbiota
Language	English
Publishing date	2022-02-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1042384-9
ISSN	1879-3061 ; 1043-2760
ISSN (online)	1879-3061
ISSN	1043-2760
DOI	10.1016/j.tem.2022.01.002
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