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Article ; Online: High-mobility group box-1 impedes skeletal muscle regeneration via downregulation of Pax-7 synthesis by increasing miR-342-5p expression.

Ho, Trung-Loc / Lai, Yu-Liang / Hsu, Chin-Jung / Su, Chen-Ming / Tang, Chih-Hsin

Aging

2023 Volume 15, Issue 21, Page(s) 12618–12632

Abstract: High mobility group box-1 (HMGB1) is a driver of inflammation in various muscular diseases. In a previous study, we determined that HMGB1 induced the atrophy of skeletal muscle by impairing myogenesis. Skeletal muscle regeneration after injury is ... ...

Abstract	High mobility group box-1 (HMGB1) is a driver of inflammation in various muscular diseases. In a previous study, we determined that HMGB1 induced the atrophy of skeletal muscle by impairing myogenesis. Skeletal muscle regeneration after injury is dependent on pair box 7 (Pax-7)-mediated myogenic differentiation. In the current study, we determined that the HMGB1-induced downregulation of Pax-7 expression in myoblasts inhibited the regeneration of skeletal muscle. We also determined that HMGB1 inhibits Pax-7 and muscle differentiation by increasing miR-342-5p synthesis via receptors for advanced glycation end-products (RAGE), toll-like receptor (TLR) 2, TLR4, and c-Src signaling pathways. In a mouse model involving glycerol-induced muscle injury, the therapeutic inhibition of HMGB1 was shown to rescue Pax-7 expression and muscle regeneration. The HMGB1/Pax-7 axis is a promising therapeutic target to promote muscular regeneration.
MeSH term(s)	Mice ; Animals ; Down-Regulation ; HMGB1 Protein/genetics ; HMGB1 Protein/metabolism ; Wound Healing ; Muscle, Skeletal/metabolism ; Muscular Diseases ; MicroRNAs/genetics
Chemical Substances	HMGB1 Protein ; MicroRNAs
Language	English
Publishing date	2023-11-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.205202
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Article ; Online: FGF23 facilitates IL-1β synthesis in rheumatoid arthritis through activating PI3K, Akt, and NF-κB pathways.

Hu, Sung-Lin / Thadevoos, Louis Anoop / Ho, Trung-Loc / Lin, Yen-You / Chen, Hsien-Te / Huang, Chien-Chung / Su, Chen-Ming / Tang, Chih-Hsin

Environmental toxicology

2024 Volume 39, Issue 6, Page(s) 3283–3291

Abstract: Rheumatoid arthritis (RA) is a well-known autoimmune disorder related with joint pain, joint swelling, cartilage and bone degradation as well as deformity. Fibroblast growth factor 23 (FGF23) is an endocrine factor of the FGF family primarily produced by ...

Abstract	Rheumatoid arthritis (RA) is a well-known autoimmune disorder related with joint pain, joint swelling, cartilage and bone degradation as well as deformity. Fibroblast growth factor 23 (FGF23) is an endocrine factor of the FGF family primarily produced by osteocytes and osteoblasts, involves an essential effect in pathogenesis of RA. IL-1β is a vital proinflammatory factor in the development of RA. However, the role of FGF23 on IL-1β synthesis in RA has not been fully explored. Our analysis of database revealed higher levels of FGF23 and IL-1β in RA samples compared with healthy controls. High-throughput screening demonstrated that IL-1β is a potential candidate factor after FGF23 treatment in RA synovial fibroblasts (RASFs). FGF23 concentration dependently promotes IL-1β synthesis in RASFs. FGF23 enhances IL-1β expression by activating the PI3K, Akt, and NF-κB pathways. Our findings support the notion that FGF23 is a promising target in the remedy of RA.
MeSH term(s)	Fibroblast Growth Factor-23 ; Arthritis, Rheumatoid/metabolism ; Interleukin-1beta/metabolism ; Fibroblast Growth Factors/metabolism ; Humans ; Proto-Oncogene Proteins c-akt/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; NF-kappa B/metabolism ; Signal Transduction/drug effects ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Cells, Cultured ; Synovial Membrane/drug effects ; Synovial Membrane/metabolism ; Female ; Male
Language	English
Publishing date	2024-02-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	1463449-1
ISSN	1522-7278 ; 1520-4081
ISSN (online)	1522-7278
ISSN	1520-4081
DOI	10.1002/tox.24180
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Article ; Online: Melatonin improves muscle injury and differentiation by increasing Pax7 expression.

Su, Chen-Ming / Tsai, Chun-Hao / Chen, Hsien-Te / Wu, Yi-Syuan / Chang, Jun-Way / Yang, Shun-Fa / Tang, Chih-Hsin

International journal of biological sciences

2023 Volume 19, Issue 4, Page(s) 1049–1062

Abstract: A balance between muscle injury and regeneration is critical for sustaining muscle function during myogenesis. Melatonin is well recognized for its involvement in neuroprotective activities, immune system regulation and suppression of inflammatory ... ...

Abstract	A balance between muscle injury and regeneration is critical for sustaining muscle function during myogenesis. Melatonin is well recognized for its involvement in neuroprotective activities, immune system regulation and suppression of inflammatory responses. This study set out to provide evidence that melatonin improves muscle regeneration during skeletal muscle differentiation. We began with cloning a stable cell line expressing Pax7 knockdown C2C12 cells. We then investigated markers of muscle degradation and regeneration after treating growth medium and differentiated medium with melatonin. Bioinformatics analysis of RNA sequencing results revealed that melatonin regulates muscle differentiation and that Wnt cascades are involved in the mechanism of muscle differentiation. Screening of miRNA online databases revealed that miR-3475-3p is a specific binding site on Pax7 and acts as a negative regulator of Pax7, which is involved in melatonin-induced muscle differentiation. We then investigated the effects of melatonin treatment in the early stage of glycerol-induced skeletal muscle injury in mice. Rotarod performance, micro-computed tomography and immunohistochemistry findings showed that melatonin-induced increases in Pax7 expression rapidly rescue skeletal muscle differentiation and improve muscle fiber morphology in glycerol-induced muscle injury. Our data support the hypothesis that melatonin rapidly rescues skeletal muscle differentiation and the melatonin/Pax7 axis could therefore serve as an important therapeutic target to optimize muscle healing after injury.
MeSH term(s)	Animals ; Mice ; Melatonin/pharmacology ; Melatonin/therapeutic use ; Melatonin/metabolism ; Glycerol/metabolism ; X-Ray Microtomography ; Myoblasts/metabolism ; Cell Differentiation/genetics ; Muscle, Skeletal ; Muscle Development/genetics ; Cell Proliferation ; PAX7 Transcription Factor/genetics ; PAX7 Transcription Factor/metabolism
Chemical Substances	Melatonin (JL5DK93RCL) ; Glycerol (PDC6A3C0OX) ; Pax7 protein, mouse ; PAX7 Transcription Factor
Language	English
Publishing date	2023-01-22
Publishing country	Australia
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2179208-2
ISSN	1449-2288 ; 1449-2288
ISSN (online)	1449-2288
ISSN	1449-2288
DOI	10.7150/ijbs.79169
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Article ; Online: The joint effects of physical activity and sleep duration on risk of osteoporosis in Taiwanese adult population: The Taiwan Biobank Study.

Chen, Kun-Hui / Su, Chen-Ming / Liu, Wei-Ju / Tzeng, Huey-En / Lee, Chia-Lin / Tsai, Chun-Hao

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA

2023 Volume 35, Issue 3, Page(s) 523–531

Abstract: Most studies investigating the association between physical activity and osteoporosis prevention only focused on specific types of physical activity. This study's evidence regarding the combined effects or interaction of sleep duration and physical ... ...

Abstract	Most studies investigating the association between physical activity and osteoporosis prevention only focused on specific types of physical activity. This study's evidence regarding the combined effects or interaction of sleep duration and physical activity. The findings emphasize the role of sleep duration and physical activity in association with osteoporosis. Purpose: The associations between physical activity, sleep duration, and prevalent osteoporosis in Taiwanese adults were studied in this cross-sectional study. Methods: The Taiwan Biobank enrolled a community-based cohort of ~ 120,000 volunteers (as of April 30, 2020) between 30 and 76 years of age with no history of cancer. Amongst, bone mineral density (BMD) measures by dual-energy X-ray absorptiometry (DXA) were available in 22,402 participants. After excluding individuals who had no complete data of BMI (n = 23), MET score (n = 207), T-score (n = 8,826), and sleep duration (n = 16), 13,330 subjects were included as the primary cohort. Univariate and multivariable regression analyses were performed to determine the associations between the presence of osteoporosis, physical activity level, sleep duration, and other variables. Results: The results showed that after adjustment, subjects with physical activity < 20 METs/week and ≥ 20 METs/week (aOR = 1.017 and 0.767, respectively) were associated with risk of osteoporosis than those with zero MET. The odds of osteoporosis were not significantly lower in subjects who slept for ≥ 8 h/day (aOR = 0.934,p=0.266). In addition, compared to short sleepers with no physical activity, adults with increased physical activity ≥ 20 METs/week and sleep ≥ 8 h/day had a significantly lowest likelihood of osteoporosis (aOR = 0.702). Those with medium physical activity (< 20 METs/week) plus average sleep duration (6.5-8 h/day) did not have significant higher odds of osteoporosis (aOR = 1.129,p=0.151). Conclusion: The findings emphasize the joint role of sleep duration and physical activity in association with osteoporosis. Adults with high physical activity plus high sleep hours have the highest BMD and lowest risk of osteoporosis.
MeSH term(s)	Adult ; Humans ; Sleep Duration ; Taiwan/epidemiology ; Cross-Sectional Studies ; Biological Specimen Banks ; Osteoporosis/etiology ; Osteoporosis/complications ; Bone Density ; Absorptiometry, Photon ; Exercise
Language	English
Publishing date	2023-11-10
Publishing country	England
Document type	Journal Article
ZDB-ID	1064892-6
ISSN	1433-2965 ; 0937-941X
ISSN (online)	1433-2965
ISSN	0937-941X
DOI	10.1007/s00198-023-06947-9
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Zs.A 3163: Show issues

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Article ; Online: HMGB1 Promotes In Vitro and In Vivo Skeletal Muscle Atrophy through an IL-18-Dependent Mechanism.

Ho, Trung-Loc / Tang, Chih-Hsin / Chang, Sunny Li-Yun / Tsai, Chun-Hao / Chen, Hsien-Te / Su, Chen-Ming

Cells

2022 Volume 11, Issue 23

Abstract: Skeletal muscle atrophy occurs due to muscle wasting or reductions in protein associated with aging, injury, and inflammatory processes. High-mobility group box-1 (HMGB1) protein is passively released from necrotic cells and actively secreted by ... ...

Abstract	Skeletal muscle atrophy occurs due to muscle wasting or reductions in protein associated with aging, injury, and inflammatory processes. High-mobility group box-1 (HMGB1) protein is passively released from necrotic cells and actively secreted by inflammatory cells, and is implicated in the pathogenesis of various inflammatory and immune diseases. HMGB1 is upregulated in muscle inflammation, and circulating levels of the proinflammatory cytokine interleukin-18 (IL-18) are upregulated in patients with sarcopenia, a muscle-wasting disease. We examined whether an association exists between HMGB1 and IL-18 signaling in skeletal muscle atrophy. HMGB1-induced increases of IL-18 levels enhanced the expression of muscle atrophy markers and inhibited myogenic marker expression in C2C12 and G7 myoblast cell lines. HMGB1-induced increases of IL-18 production in C2C12 cells involved the RAGE/p85/Akt/mTOR/c-Jun signaling pathway. HMGB1 short hairpin RNA (shRNA) treatment rescued the expression of muscle-specific differentiation markers in murine C2C12 myotubes and in mice with glycerol-induced muscle atrophy. HMGB1 and IL-18 signaling was suppressed in the mice after HMGB1 shRNA treatment. These findings suggest that the HMGB1/IL-18 axis is worth targeting for the treatment of skeletal muscle atrophy.
Language	English
Publishing date	2022-12-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11233936
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Article ; Online: Melatonin abolished proinflammatory factor expression and antagonized osteoarthritis progression in vivo.

Liu, Shan-Chi / Tsai, Chun-Hao / Wang, Yu-Han / Su, Chen-Ming / Wu, Hsi-Chin / Fong, Yi-Chin / Yang, Shun-Fa / Tang, Chih-Hsin

Cell death & disease

2022 Volume 13, Issue 3, Page(s) 215

Abstract: Progressive structural changes in osteoarthritis (OA) involve synovial inflammation and angiogenesis, as well as activation of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin (IL)-8, and the angiogenic factor vascular ... ...

Abstract	Progressive structural changes in osteoarthritis (OA) involve synovial inflammation and angiogenesis, as well as activation of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin (IL)-8, and the angiogenic factor vascular endothelial growth factor (VEGF). The endogenous hormone melatonin (N-acetyl-5-methoxytryptamine) is involved in antioxidative and anti-inflammatory activities, but how it antagonizes OA progression via its specific receptors is unclear. Here, we demonstrate that the MT
MeSH term(s)	Animals ; Fibroblasts/metabolism ; Melatonin/metabolism ; Melatonin/pharmacology ; Osteoarthritis/genetics ; Osteoarthritis/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Rats ; Synovial Membrane/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Vascular Endothelial Growth Factor A/metabolism
Chemical Substances	Tumor Necrosis Factor-alpha ; Vascular Endothelial Growth Factor A ; Melatonin (JL5DK93RCL)
Language	English
Publishing date	2022-03-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-022-04656-5
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Article ; Online: Impact of CCL4 gene polymorphisms upon the progression of lung cancer in a Han Chinese cohort.

Hu, Weiwei / Chien, Szu-Yu / Ying, Pengqing / Liu, Po-I / Su, Chen-Ming / Tang, Chih-Hsin

Medicine

2020 Volume 99, Issue 3, Page(s) e18906

Abstract: Lung cancer is the most common malignancy in China and has a low survival rate amongst Han Chinese. The high mortality is largely attributed to late-stage diagnosis, when treatment is largely ineffective. Identification of genetic variants could ... ...

Abstract	Lung cancer is the most common malignancy in China and has a low survival rate amongst Han Chinese. The high mortality is largely attributed to late-stage diagnosis, when treatment is largely ineffective. Identification of genetic variants could potentially assist with earlier diagnosis and thus more effective treatment. Chemokine (C-C motif) ligand 4 (CCL4) plays a critical role as a chemoattractant in tumor development, metastasis and angiogenesis. In this study, we explored three CCL4 single nucleotide polymorphisms (SNPs) (rs1634507, rs1719153, and rs10491121) in 538 patients with lung cancer and 370 healthy, cancer-free controls. Carriers of the GT + TT heterozygote of rs1634507 had a lower risk of lung cancer than wild-type (GG) carriers, while the presence of the AG + GG heterozygote at rs10491121 was associated with a higher risk of lung cancer compared with having the AA genotype. The G/A/G and T/A/A CCL4 haplotypes significantly reduced and increased the risks for lung cancer, respectively. Our study is the first to document correlations between CCL4 polymorphisms and lung cancer development and progression in people of Han Chinese ethnicity.
MeSH term(s)	Adult ; Asian Continental Ancestry Group/genetics ; Case-Control Studies ; Chemokine CCL4/genetics ; China ; Disease Progression ; Female ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Lung Neoplasms/genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide
Chemical Substances	CCL4 protein, human ; Chemokine CCL4
Language	English
Publishing date	2020-02-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	80184-7
ISSN	1536-5964 ; 0025-7974
ISSN (online)	1536-5964
ISSN	0025-7974
DOI	10.1097/MD.0000000000018906
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Article ; Online: Nesfatin-1 Stimulates CCL2-dependent Monocyte Migration And M1 Macrophage Polarization: Implications For Rheumatoid Arthritis Therapy.

Chang, Jun-Way / Liu, Shan-Chi / Lin, Yen-You / He, Xiu-Yuan / Wu, Yi-Syuan / Su, Chen-Ming / Tsai, Chun-Hao / Chen, Hsien-Te / Fong, Yi-Ching / Hu, Sung-Lin / Huang, Chien-Chung / Tang, Chih-Hsin

International journal of biological sciences

2023 Volume 19, Issue 1, Page(s) 281–293

Abstract: Rheumatoid arthritis (RA) is a prototypic inflammatory disease, characterized by the infiltration of proinflammatory cytokines into the joint synovium and the migration of mononuclear cells into inflammatory sites. The adipokine nesfatin-1 is linked to ... ...

Abstract	Rheumatoid arthritis (RA) is a prototypic inflammatory disease, characterized by the infiltration of proinflammatory cytokines into the joint synovium and the migration of mononuclear cells into inflammatory sites. The adipokine nesfatin-1 is linked to inflammatory events in various diseases, although its role in RA pathology is uncertain. Analysis of the Gene Expression Omnibus GSE55235 dataset revealed high levels of expression of the adipokine nesfatin-1 in human RA synovial tissue. Similarly, our human synovial tissue samples exhibited increasing levels of nesfatin-1 expression and
MeSH term(s)	Humans ; Mice ; Animals ; Monocytes/metabolism ; Arthritis, Rheumatoid/genetics ; Arthritis, Rheumatoid/metabolism ; Cytokines/metabolism ; Macrophages/metabolism ; Adipokines/metabolism ; Chemokine CCL2/metabolism
Chemical Substances	Cytokines ; Adipokines ; CCL2 protein, human ; Chemokine CCL2
Language	English
Publishing date	2023-01-01
Publishing country	Australia
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2179208-2
ISSN	1449-2288 ; 1449-2288
ISSN (online)	1449-2288
ISSN	1449-2288
DOI	10.7150/ijbs.77987
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Article ; Online: RAD52 gene polymorphisms are associated with risk of colorectal cancer in a Chinese Han population.

Zhang, Longyi / Zhang, Yongjun / Tang, Chih-Hsin / Su, Chen-Ming

Medicine

2018 Volume 96, Issue 49, Page(s) e8994

Abstract: Upward trends in the incidence and mortality rates of colorectal cancer (CRC) in China over the past decade mean that it is critical to improve survival outcomes for patients with this malignancy. Analysis of genetic variants may identify biomarkers that ...

Abstract	Upward trends in the incidence and mortality rates of colorectal cancer (CRC) in China over the past decade mean that it is critical to improve survival outcomes for patients with this malignancy. Analysis of genetic variants may identify biomarkers that have a role in CRC susceptibility and clinical outcomes in Chinese patients with CRC. RAD52 is a key mediator during DNA strand exchange and homologous recombination within mammalian cells. In this study, we explored the effects of RAD52 single nucleotide polymorphisms (SNPs) in the susceptibility and clinicopathological characteristics of Chinese Han patients with CRC. Five RAD52 SNPs (rs1051669, rs10774474, rs11571378, rs6489769, and rs7963551) were analyzed using TaqMan SNP genotyping in 281 patients with CRC and 309 healthy controls. Among those aged over 60 years in the total population, carriers of the variant C allele or at least one T allele of the rs1051669 SNP were at a lower risk of CRC than carriers of the wild-type CC variant of rs1051669, while in those carrying the rs7963551 SNP, the GT or GT+GG alleles were associated with an increased risk of CRC compared with patients carrying TT alleles. We indicated a significant correlation between RAD52 rs7963551 polymorphism and lymph node metastasis in CRC patients. In all patients, the T-T-T-T-T, C-T-T-T-T, and C-T-A-C-T haplotypes were associated with an increasing risk of CRC. Our findings suggest that 4 RAD52 SNPs (rs1051669, rs10774474, rs11571378, and rs6489769) might contribute to the prediction of CRC susceptibility. In conclusion, our study demonstrated that RAD52 polymorphisms were associated with CRC in a Chinese Han cohort.
MeSH term(s)	Aged ; Alleles ; Asians/genetics ; Case-Control Studies ; China/epidemiology ; Colorectal Neoplasms/ethnology ; Colorectal Neoplasms/genetics ; Female ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Rad52 DNA Repair and Recombination Protein/genetics ; Real-Time Polymerase Chain Reaction
Chemical Substances	RAD52 protein, human ; Rad52 DNA Repair and Recombination Protein
Language	English
Publishing date	2018-01-11
Publishing country	United States
Document type	Journal Article ; Observational Study
ZDB-ID	80184-7
ISSN	1536-5964 ; 0025-7974
ISSN (online)	1536-5964
ISSN	0025-7974
DOI	10.1097/MD.0000000000008994
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Article ; Online: Association between Angiopoietin-2 Gene Polymorphisms and Susceptibility to Coronary Artery Disease.

Lan, Luhang / Kang, Le / Lu, Liang / Ge, Xuan / Si, Hongping / Peng, Jiren / Wang, Maofeng / Li, Weimin / Su, Chen-Ming

Archives of Iranian medicine

2021 Volume 24, Issue 8, Page(s) 622–628

Abstract: Background: Angiopoietin-2 (Angpt2) is associated with the progression of coronary artery disease (CAD). This research aimed to investigate the possible association between single nucleotide polymorphisms (SNPs) of : Methods: This research was ... ...

Abstract	Background: Angiopoietin-2 (Angpt2) is associated with the progression of coronary artery disease (CAD). This research aimed to investigate the possible association between single nucleotide polymorphisms (SNPs) of Methods: This research was performed in a hospital from the eastern region of China. From February 2019 to June 2019, 222 patients with CAD were newly diagnosed and 403 healthy controls were confirmed by physical examinations. The distribution frequency of five SNPs of the Results: Our data showed that the participants with the TT genotype of rs2442598 were at reduced risk of CAD compared with wild-types (adjusted odds ratio [AOR] = 0.511, 95% CI: 0.283-0.923). The participants with the AC and AC+CC genotypes of rs11137037 were at greater risk of CAD compared to wild-types (AOR = 1.754, 95% CI: 1.140-2.699; AOR = 1.731, 95% CI: 1.165-2.573, respectively). In addition, carriers of the GG+TT genotypes of rs12674822, showed more significant high-density lipoprotein than those of GG genotype, in addition, carriers of the GG+TT genotypes of rs12674822, showed more significant high-density lipoprotein than those of GG genotype ( Conclusion: These findings, as well as analysis of the haplotype, clearly indicate that
MeSH term(s)	Angiopoietin-2/genetics ; Asians/genetics ; Case-Control Studies ; China/epidemiology ; Coronary Artery Disease/genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Polymorphism, Single Nucleotide
Chemical Substances	Angiopoietin-2
Language	English
Publishing date	2021-08-01
Publishing country	Iran
Document type	Journal Article
ZDB-ID	2204979-4
ISSN	1735-3947 ; 1029-2977
ISSN (online)	1735-3947
ISSN	1029-2977
DOI	10.34172/aim.2021.88
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