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Article ; Online: Novel genetic variants in long non-coding RNA MEG3 are associated with the risk of asthma

Kuo-Liang Chiu / Wen-Shin Chang / Chia-Wen Tsai / Mei-Chin Mong / Te-Chun Hsia / Da-Tian Bau

PeerJ, Vol 11, p e

2023 Volume 14760

Abstract: Background Asthma is the most common chronic inflammatory airway disease worldwide. Asthma is a complex disease whose exact etiologic mechanisms remain elusive; however, it is increasingly evident that genetic factors play essential roles in the ... ...

Abstract	Background Asthma is the most common chronic inflammatory airway disease worldwide. Asthma is a complex disease whose exact etiologic mechanisms remain elusive; however, it is increasingly evident that genetic factors play essential roles in the development of asthma. The purpose of this study is to identify novel genetic susceptibility loci for asthma in Taiwanese. We selected a well-studied long non-coding RNA (lncRNA), MEG3, which is involved in multiple cellular functions and whose expression has been associated with asthma. We hypothesize that genetic variants in MEG3 may influence the risk of asthma. Methods We genotyped four single nucleotide polymorphisms (SNPs) in MEG3, rs7158663, rs3087918, rs11160608, and rs4081134, in 198 patients with asthma and 453 healthy controls and measured serum MEG3 expression level in a subset of controls. Results The variant AG and AA genotypes of MEG3 rs7158663 were significantly over-represented in the patients compared to the controls (P = 0.0024). In logistic regression analyses, compared with the wild-type GG genotype, the heterozygous variant genotype (AG) was associated with a 1.62-fold [95% confidence interval (CI) [1.18–2.32], P = 0.0093] increased risk and the homozygous variant genotype (AA) conferred a 2.68-fold (95% CI [1.52–4.83], P = 0.003) increased risk of asthma. The allelic test showed the A allele was associated with a 1.63-fold increased risk of asthma (95% CI [1.25–2.07], P = 0.0004). The AG plus AA genotypes were also associated with severe symptoms (P = 0.0148). Furthermore, the AG and AA genotype carriers had lower serum MEG3 expression level than the GG genotype carriers, consistent with the reported downregulation of MEG3 in asthma patients. Conclusion MEG3 SNP rs7158663 is a genetic susceptibility locus for asthma in Taiwanese. Individuals carrying the variant genotypes have lower serum MEG3 level and are at increased risks of asthma and severe symptoms.
Keywords	Asthma ; Genotype ; MEG3 ; Polymorphism ; Transcriptional expression ; Medicine ; R ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	PeerJ Inc.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Interaction of a Novel Alternatively Spliced Variant of HSD11B1L with Parkin Enhances the Carcinogenesis Potential of Glioblastoma

Ru-Huei Fu / Syuan-Yu Hong / Chia-Wen Tsai / Shih-Ping Liu / Shao-Chih Chiu / Meng-Zhen Wu / Woei-Cherng Shyu / Shinn-Zong Lin

Cells, Vol 12, Iss 894, p

Peiminine Interferes with This Interaction

2023 Volume 894

Abstract: Glioblastoma (GBM) is a primary brain tumor of unknown etiology. It is extremely aggressive, incurable and has a short average survival time for patients. Therefore, understanding the precise molecular mechanisms of this diseases is essential to ... ...

Abstract	Glioblastoma (GBM) is a primary brain tumor of unknown etiology. It is extremely aggressive, incurable and has a short average survival time for patients. Therefore, understanding the precise molecular mechanisms of this diseases is essential to establish effective treatments. In this study, we cloned and sequenced a splice variant of the hydroxysteroid 11-β dehydrogenase 1 like gene ( HSD11B1L ) and named it HSD11B1L-181. HSD11 B1L-181 was specifically expressed only in GBM cells. Overexpression of this variant can significantly promote the proliferation, migration and invasion of GBM cells. Knockdown of HSD11B1L-181 expression inhibited the oncogenic potential of GBM cells. Furthermore, we identified the direct interaction of parkin with HSD11B1L-181 by screening the GBM cDNA expression library via yeast two-hybrid. Parkin is an RBR E3 ubiquitin ligase whose mutations are associated with tumorigenesis. Small interfering RNA treatment of parkin enhanced the proliferative, migratory and invasive abilities of GBM. Finally, we found that the alkaloid peiminine from the bulbs of Fritillaria thunbergii Miq blocks the interaction between HSD11B1L-181 and parkin, thereby lessening carcinogenesis of GBM. We further confirmed the potential of peiminine to prevent GBM in cellular, ectopic and orthotopic xenograft mouse models. Taken together, these findings not only provide insight into GBM, but also present an opportunity for future GBM treatment.
Keywords	glioblastoma ; alternative splicing ; hydroxysteroid 11-β-dehydrogenase 1 like gene (HSD11B1L) ; proliferation ; migration ; invasion ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Genome-Wide Association Study Identified Novel Genetic Susceptibility Loci for Oral Cancer in Taiwan

Da-Tian Bau / Ting-Yuan Liu / Chia-Wen Tsai / Wen-Shin Chang / Jian Gu / Jai-Sing Yang / Liang-Chun Shih / Fuu-Jen Tsai

International Journal of Molecular Sciences, Vol 24, Iss 2789, p

2023 Volume 2789

Abstract: Taiwan has the highest incidence rate of oral cancer in the world. Although oral cancer is mostly an environmentally induced cancer, genetic factors also play an important role in its etiology. Genome-wide association studies (GWAS) have identified nine ... ...

Abstract	Taiwan has the highest incidence rate of oral cancer in the world. Although oral cancer is mostly an environmentally induced cancer, genetic factors also play an important role in its etiology. Genome-wide association studies (GWAS) have identified nine susceptibility regions for oral cancers in populations of European descent. In this study, we performed the first GWAS of oral cancer in Taiwan with 1529 cases and 44,572 controls. We confirmed two previously reported loci on the 6p21.33 (HLA-B) and 6p21.32 (HLA-DQ gene cluster) loci, highlighting the importance of the human leukocyte antigen and, hence, the immunologic mechanisms in oral carcinogenesis. The TERT-CLMPT1L locus on 5p15.33, the 4q23 ADH1B locus, and the LAMC3 locus on 9q34.12 were also consistent in the Taiwanese. We found two new independent loci on 6p21.32, rs401775 in SKIV2L gene and rs9267798 in TNXB gene. We also found two suggestive novel Taiwanese-specific loci near the TPRS1 gene on 8q23.3 and in the TMED3 gene on 15q25.1. This study identified both common and unique oral cancer susceptibility loci in the Taiwanese as compared to populations of European descent and shed significant light on the etiology of oral cancer in Taiwan.
Keywords	oral cancer ; genome-wide association study ; SNP ; HLA ; TERT ; TPRS1 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Non-Homologous End-Joining Pathway Genotypes Significantly Associated with Nasopharyngeal Carcinoma Susceptibility

Chia-Wen Tsai / Liang-Chun Shih / Wen-Shin Chang / Che-Lun Hsu / Jie-Long He / Te-Chun Hsia / Yun-Chi Wang / Jian Gu / Da-Tian Bau

Biomedicines, Vol 11, Iss 1648, p

2023 Volume 1648

Abstract: Defects in the non-homologous end-joining (NHEJ) DNA repair pathway lead to genomic instability and carcinogenesis. However, the roles of individual NHEJ genes in nasopharyngeal carcinoma (NPC) etiology are not well-understood. The aim of this study was ... ...

Abstract	Defects in the non-homologous end-joining (NHEJ) DNA repair pathway lead to genomic instability and carcinogenesis. However, the roles of individual NHEJ genes in nasopharyngeal carcinoma (NPC) etiology are not well-understood. The aim of this study was to assess the contribution of NHEJ genotypes, including XRCC4 (rs6869366, rs3734091, rs28360071, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and Ligase4 rs1805388, to NPC risk, with 208 NPC patients and 416 controls. Genotype–phenotype correlations were also investigated by measuring mRNA and protein expression in adjacent normal tissues and assessing the NHEJ repair capacity in blood lymphocytes from 43 NPC patients. The results showed significant differences in the distributions of variant genotypes at XRCC4 rs3734091, rs28360071, and XRCC6 rs2267437 between the cases and controls. The variant genotypes of these three polymorphisms were associated with significantly increased NPC risks. NPC patients with the risk genotypes at XRCC6 rs2267437 had significantly reduced expression levels of both mRNA and protein, as well as a lower NHEJ repair capacity, than those with the wild-type genotype. In conclusion, XRCC4 rs3734091, rs28360071, and XRCC6 rs2267437 in the NHEJ pathway were associated with NPC susceptibility. XRCC6 rs2267437 can modulate mRNA and protein expression and the NHEJ repair capacity.
Keywords	DNA repair ; genotype ; nasopharyngeal carcinoma ; non-homologous end-joining ; polymorphism ; Biology (General) ; QH301-705.5
Subject code	610 ; 616
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cathelicidin Antimicrobial Peptide Acts as a Tumor Suppressor in Hepatocellular Carcinoma

Lien-Hung Huang / Cheng-Shyuan Rau / Yueh-Wei Liu / Hui-Ping Lin / Yi-Chan Wu / Chia-Wen Tsai / Peng-Chen Chien / Chia-Jung Wu / Chun-Ying Huang / Ting-Min Hsieh / Ching-Hua Hsieh

International Journal of Molecular Sciences, Vol 24, Iss 21, p

2023 Volume 15652

Abstract: Hepatocellular carcinoma (HCC) is associated with high rates of metastasis and recurrence, and is one of the most common causes of cancer-associated death worldwide. This study examined the protein changes within circulating exosomes in patients with HCC ...

Abstract	Hepatocellular carcinoma (HCC) is associated with high rates of metastasis and recurrence, and is one of the most common causes of cancer-associated death worldwide. This study examined the protein changes within circulating exosomes in patients with HCC against those in healthy people using isobaric tags for a relative or absolute quantitation (iTRAQ)-based quantitative proteomics analysis. The protein levels of von Willebrand factor (VWF), cathelicidin antimicrobial peptide (CAMP), and proteasome subunit beta type-2 (PSMB2) were altered in HCC. The increased levels of VWF and PSMB2 but decreased CAMP levels in the serum of patients with HCC were validated by enzyme-linked immunosorbent assays. The level of CAMP (the only cathelicidin found in humans) also decreased in the circulating exosomes and buffy coat of the HCC patients. The serum with reduced levels of CAMP protein in the HCC patients increased the cell proliferation of Huh-7 cells; this effect was reduced following the addition of CAMP protein. The depletion of CAMP proteins in the serum of healthy people enhances the cell proliferation of Huh-7 cells. In addition, supplementation with synthetic CAMP reduces cell proliferation in a dose-dependent manner and significantly delays G1-S transition in Huh-7 cells. This implies that CAMP may act as a tumor suppressor in HCC.
Keywords	HCC (hepatocellular carcinoma) ; iTRAQ (isobaric tags for relative or absolute quantitation) ; CAMP (cathelicidin antimicrobial peptide) ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Stone weirs in Penghu and adaption to tourism development

Shyi-Liang Yu / Ying-Chien Chu / Chia-Wen Tsai

Journal of Ecology and Environment, Vol 38, Iss 2, Pp 257-

2015 Volume 262

Abstract: The ancient fishing methods include stone fish weir, beach seine and baulk net, but the fish catches of the stone fish weir is the most abundant. The stone fish weirs not only constitute important landscape, but also are representative of the fishery ... ...

Abstract	The ancient fishing methods include stone fish weir, beach seine and baulk net, but the fish catches of the stone fish weir is the most abundant. The stone fish weirs not only constitute important landscape, but also are representative of the fishery culture in Penghu, because they are fishing ground built by ancient people to take advantage of natural environment and resources. The objectives of this study is to understand the relevance of stone fish weirs in Penghu and to preserve biological diversity, as well as the value of stone fish weirs in Penghu fishery culture, and further make suggestions on the stone fish weirs. According to the present study, the marine species around the stone fish weirs tend to be diversifying, and in the future the region’s economy can be revitalized by sightseeing, which may promote the ecotourism, and also volunteer tourism. In the future, stone fish weirs must be promoted as a sightseeing destination. Also, by taking into consideration the experience of the Jibei stone weir protection team, the local communities of Penghu can have their own protection team to revitalize the stone fish weirs for sustainable operation and management.
Keywords	Penghu ; stone weirs ; sustainable management ; volunteer tourism ; Ecology ; QH540-549.5 ; Biology (General) ; QH301-705.5 ; Science ; Q
Subject code	910
Language	English
Publishing date	2015-05-01T00:00:00Z
Publisher	The Korean Society of Fisheries and Aquatic Science
Document type	Article ; Online
DOI	10.5141/ecoenv.2015.026
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Protective Effects of Jujubosides on 6-OHDA-Induced Neurotoxicity in SH-SY5Y and SK-N-SH Cells

Chao-Hsuan Chen / Pei-Chen Hsu / Shih-Wei Hsu / Kun-Ting Hong / Kai-Yuan Chen / Jie-Long He / Der-Yang Cho / Yun-Chi Wang / Wen-Shin Chang / Da-Tian Bau / Chia-Wen Tsai

Molecules, Vol 27, Iss 4106, p

2022 Volume 4106

Abstract: 6-hydroxydopamine (6-OHDA) is used to induce oxidative damage in neuronal cells, which can serve as an experimental model of Parkinson’s disease (PD). Jujuboside A and B confer free radical scavenging effects but have never been examined for their ... ...

Abstract	6-hydroxydopamine (6-OHDA) is used to induce oxidative damage in neuronal cells, which can serve as an experimental model of Parkinson’s disease (PD). Jujuboside A and B confer free radical scavenging effects but have never been examined for their neuroprotective effects, especially in PD; therefore, in this study, we aimed to investigate the feasibility of jujubosides as protectors of neurons against 6-OHDA and the underlying mechanisms. 6-OHDA-induced neurotoxicity in the human neuronal cell lines SH-SY5Y and SK-N-SH, was used to evaluate the protective effects of jujubosides. These findings indicated that jujuboside A and B were both capable of rescuing the 6-OHDA-induced loss of cell viability, activation of apoptosis, elevation of reactive oxygen species, and downregulation of the expression levels of superoxide dismutase, catalase, and glutathione peroxidase. In addition, jujuboside A and B can reverse a 6-OHDA-elevated Bax/Bcl-2 ratio, downregulate phosphorylated PI3K and AKT, and activate caspase-3, -7, and -9. These findings showed that jujubosides were capable of protecting both SH-SY5Y and SK-N-SH neuronal cells from 6-OHDA-induced toxicity via the rebalancing of the redox system, together with the resetting of the PI3K/AKT apoptotic signaling cascade. In conclusion, jujuboside may be a potential drug for PD prevention.
Keywords	apoptosis ; caspase ; 6-hydroxydopamine ; jujubosides ; Parkinson’s disease ; reactive oxygen species ; Organic chemistry ; QD241-441
Subject code	500
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Enhanced Nerve Regeneration by Exosomes Secreted by Adipose-Derived Stem Cells with or without FK506 Stimulation

Cheng-Shyuan Rau / Pao-Jen Kuo / Shao-Chun Wu / Lien-Hung Huang / Tsu-Hsiang Lu / Yi-Chan Wu / Chia-Jung Wu / Chia-Wei Lin / Chia-Wen Tsai / Ching-Hua Hsieh

International Journal of Molecular Sciences, Vol 22, Iss 8545, p

2021 Volume 8545

Abstract: Exosomes secreted by adipose-derived stem cells (ADSC-exo) reportedly improve nerve regeneration after peripheral nerve injury. Herein, we investigated whether pretreatment of ADSCs with FK506, an immunosuppressive drug that enhances nerve regeneration, ... ...

Abstract	Exosomes secreted by adipose-derived stem cells (ADSC-exo) reportedly improve nerve regeneration after peripheral nerve injury. Herein, we investigated whether pretreatment of ADSCs with FK506, an immunosuppressive drug that enhances nerve regeneration, could secret exosomes (ADSC-F-exo) that further augment nerve regeneration. Designed exosomes were topically applied to injured nerve in a mouse model of sciatic nerve crush injury to assess the nerve regeneration efficacy. Outcomes were determined by histomorphometric analysis of semi-thin nerve sections stained with toluidine blue, mouse neurogenesis PCR array, and neurotrophin expression in distal nerve segments. Isobaric tags for relative and absolute quantitation (iTRAQ) were used to profile potential exosomal proteins facilitating nerve regeneration. We observed that locally applied ADSC-exo and ADSC-F-exo significantly enhanced nerve regeneration after nerve crush injury. Pretreatment of ADSCs with FK506 failed to produce exosomes possessing more potent molecules for enhanced nerve regeneration. Proteomic analysis revealed that of 192 exosomal proteins detected in both ADSC-exo and ADSC-F-exo, histone deacetylases (HDACs), amyloid-beta A4 protein (APP), and integrin beta-1 (ITGB1) might be involved in enhancing nerve regeneration.
Keywords	sciatic nerve crush injury ; peripheral nerve regeneration ; exosome ; adipose-derived stem cells (ADSC) ; tacrolimus (FK506) ; proteomic analysis ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Exosomes Secreted by Adipose-Derived Stem Cells Following FK506 Stimulation Reduce Autophagy of Macrophages in Spine after Nerve Crush Injury

Pao-Jen Kuo / Cheng-Shyuan Rau / Shao-Chun Wu / Chia-Wei Lin / Lien-Hung Huang / Tsu-Hsiang Lu / Yi-Chan Wu / Chia-Jung Wu / Chia-Wen Tsai / Ching-Hua Hsieh

International Journal of Molecular Sciences, Vol 22, Iss 9628, p

2021 Volume 9628

Abstract: Macrophages emerge in the milieu around innervated neurons after nerve injuries. Following nerve injury, autophagy is induced in macrophages and affects the regulation of inflammatory responses. It is closely linked to neuroinflammation, while the ... ...

Abstract	Macrophages emerge in the milieu around innervated neurons after nerve injuries. Following nerve injury, autophagy is induced in macrophages and affects the regulation of inflammatory responses. It is closely linked to neuroinflammation, while the immunosuppressive drug tacrolimus (FK506) enhances nerve regeneration following nerve crush injury and nerve allotransplantation with additional neuroprotective and neurotrophic functions. The combined use of FK506 and adipose-derived stem cells (ADSCs) was employed in cell therapy for organ transplantation and vascularized composite allotransplantation. This study aimed to investigate the topical application of exosomes secreted by ADSCs following FK506 treatment (ADSC-F-exo) to the injured nerve in a mouse model of sciatic nerve crush injury. Furthermore, isobaric tags for relative and absolute quantitation (iTRAQ) were used to profile the potential exosomal proteins involved in autophagy. Immunohistochemical analysis revealed that nerve crush injuries significantly induced autophagy in the dorsal root ganglia and dorsal horn of the spinal segments. Locally applied ADSC-F-exo significantly reduced autophagy of macrophages in the spinal segments after nerve crush injury. Proteomic analysis showed that of the 22 abundant exosomal proteins detected in ADSC-F-exo, heat shock protein family A member 8 (HSPA8) and eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) are involved in exosome-mediated autophagy reduction.
Keywords	autophagy ; sciatic nerve crush injury ; exosome ; adipose-derived stem cells (ADSC) ; tacrolimus (FK506) ; proteomic analysis ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Peiminine Reduces ARTS-Mediated Degradation of XIAP by Modulating the PINK1/Parkin Pathway to Ameliorate 6-Hydroxydopamine Toxicity and α-Synuclein Accumulation in Parkinson’s Disease Models In Vivo and In Vitro

Yu-Ling Hsu / Huey-Shan Hung / Chia-Wen Tsai / Shih-Ping Liu / Yu-Ting Chiang / Yun-Hua Kuo / Woei-Cherng Shyu / Shinn-Zong Lin / Ru-Huei Fu

International Journal of Molecular Sciences, Vol 22, Iss 10240, p

2021 Volume 10240

Abstract: Parkinson’s disease (PD) is a degenerative disease that can cause motor, cognitive, and behavioral disorders. The treatment strategies being developed are based on the typical pathologic features of PD, including the death of dopaminergic (DA) neurons in ...

Abstract	Parkinson’s disease (PD) is a degenerative disease that can cause motor, cognitive, and behavioral disorders. The treatment strategies being developed are based on the typical pathologic features of PD, including the death of dopaminergic (DA) neurons in the substantia nigra of the midbrain and the accumulation of α-synuclein in neurons. Peiminine (PMN) is an extract of Fritillaria thunbergii Miq that has antioxidant and anti-neuroinflammatory effects. We used Caenorhabditis elegans and SH-SY5Y cell models of PD to evaluate the neuroprotective potential of PMN and address its corresponding mechanism of action. We found that pretreatment with PMN reduced reactive oxygen species production and DA neuron degeneration caused by exposure to 6-hydroxydopamine (6-OHDA), and therefore significantly improved the DA-mediated food-sensing behavior of 6-OHDA-exposed worms and prolonged their lifespan. PMN also diminished the accumulation of α-synuclein in transgenic worms and transfected cells. In our study of the mechanism of action, we found that PMN lessened ARTS-mediated degradation of X-linked inhibitor of apoptosis (XIAP) by enhancing the expression of PINK1/parkin. This led to reduced 6-OHDA-induced apoptosis, enhanced activity of the ubiquitin–proteasome system, and increased autophagy, which diminished the accumulation of α-synuclein. The use of small interfering RNA to down-regulate parkin reversed the benefits of PMN in the PD models. Our findings suggest PMN as a candidate compound worthy of further evaluation for the treatment of PD.
Keywords	peiminine ; Parkinson’s disease ; 6-hydroxydopamine ; α-synuclein ; apoptosis ; proteasome ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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