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Article ; Online: Incidence of Pulmonary and Respiratory Conditions in Gaucher Disease from 2000 to 2020: A Multi-institutional Cohort Study.

Huang, Yu-Nan / Huang, Jing-Yang / Liao, Wen-Ling / Chiang, Shang-Lun / Liu, Kai-Wen / Bau, DA-Tian / Wang, Chung-Hsing / Su, Pen-Hua

In vivo (Athens, Greece)

2023 Volume 37, Issue 5, Page(s) 2276–2283

Abstract: Background/aim: Gaucher disease (GD) is a rare lysosomal storage disorder that can involve the lungs and pulmonary vasculature. The long-term effects of GD on respiratory health remain unclear due to limited data on the natural history of this disease. ... ...

Abstract	Background/aim: Gaucher disease (GD) is a rare lysosomal storage disorder that can involve the lungs and pulmonary vasculature. The long-term effects of GD on respiratory health remain unclear due to limited data on the natural history of this disease. We analyzed electronic health records for 11,004 patients with GD over 10-20 years to determine the incidence of pulmonary hypertension (PH), lung disease, and other respiratory comorbidities and better understand disease course to guide management. Patients and methods: We conducted a retrospective cohort study using the TriNetX research database of 130 million international patients. The incidence of primary/secondary PH, pulmonary heart disease, interstitial/obstructive/restrictive lung disease, pulmonary hemorrhage, and pulmonary embolism was assessed in patients with GD from 2000-2020. Results: Incidence rates of all conditions assessed increased from 10 to 20 years of follow-up. Excess risk of PH, lung disease, and pulmonary hemorrhage was significantly higher in GD patients after 20 versus 10 years. Conclusion: Extended follow-up in GD is associated with substantially higher risks of PH, lung disease and other respiratory comorbidities, highlighting the need for close monitoring and early intervention to mitigate long-term pulmonary decline. Improved understanding of mechanisms driving respiratory deterioration can support the development of novel treatments to optimize outcomes in this population at high risk of pulmonary morbidity and mortality.
MeSH term(s)	Humans ; Gaucher Disease/complications ; Gaucher Disease/epidemiology ; Incidence ; Retrospective Studies ; Lung ; Lung Diseases/etiology ; Lung Diseases/complications ; Cohort Studies ; Hemorrhage/epidemiology ; Hemorrhage/etiology
Language	English
Publishing date	2023-08-29
Publishing country	Greece
Document type	Multicenter Study ; Journal Article
ZDB-ID	807031-3
ISSN	1791-7549 ; 0258-851X
ISSN (online)	1791-7549
ISSN	0258-851X
DOI	10.21873/invivo.13330
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Article ; Online: The Long-term Lung and Respiratory Outcomes of Acid Sphingomyelinase Deficiency: A 10- and 20-year Follow-up Study.

Huang, Yu-Nan / Chiang, Shang-Lun / Huang, Jing-Yang / Lu, Wen-Li / Bau, DA-Tian / Su, Pen-Hua / Wang, Chung-Hsing

In vivo (Athens, Greece)

2023 Volume 38, Issue 1, Page(s) 437–444

Abstract: Background/aim: Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder characterized by sphingomyelin accumulation causing progressive lung disease, respiratory failure, and death.: Patients and methods: This retrospective ... ...

Abstract	Background/aim: Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder characterized by sphingomyelin accumulation causing progressive lung disease, respiratory failure, and death. Patients and methods: This retrospective observational study used the TriNetX database of electronic health records for 15,108 patients with ASMD from 2000-2020. After exclusions, 8,980 individuals were followed for 10 or 20 years. Outcomes included incidence and prevalence of respiratory disorders. Associations of age, sex and race were assessed. Results: Nearly all respiratory outcomes increased significantly over 20 versus 10 years. Other respiratory disorders, specified respiratory disorders and secondary pulmonary hypertension exhibited the greatest increases, reflecting progressive lung damage in ASMD. While outcomes were poor overall, older age, male sex, and racial minority status associated with greater risks, indicating differences in disease progression or care. Conclusion: This study confirms the progressive nature of ASMD and need for close monitoring and treatment of pulmonary complications to reduce long-term morbidity and mortality. Genetic testing enabling diagnosis even for milder, adult-onset forms is critical to optimize outcomes.
MeSH term(s)	Adult ; Humans ; Male ; Follow-Up Studies ; Sphingomyelin Phosphodiesterase/genetics ; Niemann-Pick Disease, Type A/diagnosis ; Niemann-Pick Disease, Type A/genetics ; Niemann-Pick Diseases ; Lung
Chemical Substances	Sphingomyelin Phosphodiesterase (EC 3.1.4.12)
Language	English
Publishing date	2023-12-24
Publishing country	Greece
Document type	Observational Study ; Journal Article
ZDB-ID	807031-3
ISSN	1791-7549 ; 0258-851X
ISSN (online)	1791-7549
ISSN	0258-851X
DOI	10.21873/invivo.13457
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Zs.A 2288: Show issues

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Article ; Online: Prevalence of Kidney and Urinary Tract Complications in Fabry Disease from 2000 to 2020: A Global Cohort Study Including 10,637 Patients.

Tsai, Tsung-Hsun / Wang, Chung-Hsing / Chiang, Shang-Lun / Huang, Jing-Yang / Bau, DA-Tian / Huang, Yu-Nan / Su, Pen-Hua

In vivo (Athens, Greece)

2023 Volume 37, Issue 6, Page(s) 2609–2617

Abstract: Background/aim: Fabry disease, an X-linked lysosomal storage disorder, causes progressive globotriaosylceramide accumulation in cells throughout the body. Characteristic multiorgan manifestations include renal dysfunction (Fabry nephropathy) and ... ...

Abstract	Background/aim: Fabry disease, an X-linked lysosomal storage disorder, causes progressive globotriaosylceramide accumulation in cells throughout the body. Characteristic multiorgan manifestations include renal dysfunction (Fabry nephropathy) and associated urinary tract complications. Enzyme replacement therapy (ERT) has been available since 2001, but contemporary real-world data are lacking regarding Fabry nephropathy risks and treatment outcomes. Patients and methods: This retrospective cohort study analyzed electronic medical records data for 10,637 Fabry disease patients from the TriNetX research database. Kidney and urinary tract outcomes were evaluated over two decades, 2000-2010 and 2011-2020. Outcomes assessed included chronic kidney disease (CKD), urinary tract infections, urinary incontinence, obstruction, renal insufficiency, and end-stage renal disease (ESRD). Results: The prevalence of stage 4-5 CKD nearly doubled between 2000-2010 and 2011-2020, while ESRD prevalence rose over 4-fold. Incidence rates showed similar marked elevations across renal and urologic complications. Females and Black patients experienced disproportionate escalations in kidney and urinary tract morbidity. Conclusion: This large cohort study revealed significantly increased Fabry nephropathy and associated urologic complications over the past two decades, contradicting expectations of reduced morbidity with ERT availability. The findings highlight needs to optimize screening, treatment strategies, monitoring practices, and address disparities to curb rising disease burden and improve patient outcomes.
MeSH term(s)	Female ; Humans ; Fabry Disease/complications ; Fabry Disease/epidemiology ; Cohort Studies ; Retrospective Studies ; Prevalence ; alpha-Galactosidase/adverse effects ; Kidney ; Renal Insufficiency, Chronic/complications ; Renal Insufficiency, Chronic/epidemiology ; Kidney Failure, Chronic/etiology ; Kidney Failure, Chronic/complications
Chemical Substances	alpha-Galactosidase (EC 3.2.1.22)
Language	English
Publishing date	2023-10-30
Publishing country	Greece
Document type	Journal Article
ZDB-ID	807031-3
ISSN	1791-7549 ; 0258-851X
ISSN (online)	1791-7549
ISSN	0258-851X
DOI	10.21873/invivo.13368
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Article ; Online: Elucidating the Cancer Phenotype in Turner Syndrome: A 20-Year Observational Cohort Study.

Huang, Yu-Nan / Chen, Shao-Chia / Chen, Jo-Ching / Liu, Kai-Wen / Chiang, Shang-Lun / Bau, DA-Tian / Su, Pen-Hua / Wang, Chung-Hsing

Anticancer research

2023 Volume 43, Issue 11, Page(s) 5073–5081

Abstract: Background/aim: Turner syndrome confers increased cancer susceptibility; however, large-scale epidemiological evidence is lacking. This study aimed to analyze the incidence and prevalence of various malignancies in patients with Turner syndrome over 20 ... ...

Abstract	Background/aim: Turner syndrome confers increased cancer susceptibility; however, large-scale epidemiological evidence is lacking. This study aimed to analyze the incidence and prevalence of various malignancies in patients with Turner syndrome over 20 years of age to inform screening strategies. Patients and methods: We performed a retrospective cohort analysis of 11,502 patients with Turner syndrome from 2000 to 2020 utilizing the TriNetX research network database. The outcomes encompassed the incidence and prevalence of 20 cancers. Stratified analyses were used to evaluate variations in age, sex, and race. Results: Key findings demonstrated markedly elevated risks of breast (1.7%), colon (1.0%), renal (0.4%), gonadoblastoma (0.4%), and other cancers. Significant demographic variations were observed in the incidence of cancers, such as gonadoblastoma, renal, and colon cancer. Conclusion: This large real-world study offers novel insights into the spectrum of cancer risk across adulthood in Turner syndrome. Our findings elucidate Turner syndrome's complex cancer phenotype to inform clinical decision-making, prognostication, and tailored screening strategies to ultimately advance patient care.
MeSH term(s)	Humans ; Female ; Adult ; Gonadoblastoma ; Turner Syndrome/complications ; Turner Syndrome/epidemiology ; Turner Syndrome/genetics ; Retrospective Studies ; Colonic Neoplasms ; Cohort Studies ; Phenotype ; Ovarian Neoplasms
Language	English
Publishing date	2023-11-01
Publishing country	Greece
Document type	Observational Study ; Journal Article
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
DOI	10.21873/anticanres.16707
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Zs.A 1642: Show issues

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Article ; Online: T Cells Mediate Kidney Tubular Injury via Impaired PDHA1 and Autophagy in Type 1 Diabetes.

Wang, Chung-Hsing / Lu, Wen-Li / Chiang, Shang-Lun / Tsai, Tsung-Hsun / Liu, Su-Ching / Hsieh, Chia-Hung / Su, Pen-Hua / Huang, Chih-Yang / Tsai, Fuu-Jen / Lin, Yu-Jung / Huang, Yu-Nan

The Journal of clinical endocrinology and metabolism

2022 Volume 107, Issue 9, Page(s) 2556–2570

Abstract: Context: Nephropathy is a severe complication of type 1 diabetes (T1DM). However, the interaction between the PDHA1-regulated mechanism and CD4+ T cells in the early stage of kidney tubular injury remains unknown.: Objective: To evaluate the role of ... ...

Abstract	Context: Nephropathy is a severe complication of type 1 diabetes (T1DM). However, the interaction between the PDHA1-regulated mechanism and CD4+ T cells in the early stage of kidney tubular injury remains unknown. Objective: To evaluate the role of PDHA1 in the regulation of tubular cells and CD4+ T cells and further to study its interaction in tubular cell injury in T1DM. Methods: Plasma and total RNA were collected from T cells of T1DM patients (n = 35) and healthy donors (n = 33) and evaluated for neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1, PDHA1, and biomarkers of CD4+ T cells including T helper 1 cells (Th1) and regulatory T cells (Treg) markers. HK-2 cells cocultured with CD4+ T cells from T1DM patients or healthy donors (HDs) to evaluate the interaction with CD4+ T cells. Results: Increased PDHA1 gene expression levels in CD4+ T cells were positively associated with the plasma level of NGAL in T1DM patients and HDs. Our data demonstrated that the Th1/Treg subsets skewed Th1 in T1DM. Knockdown of PDHA1 in kidney tubular cells decreased ATP/ROS production, NAD/NADH ratio, mitochondrial respiration, and cell apoptosis. Furthermore, PDHA1 depletion induced impaired autophagic flux. Coculture of tubular cells and T1DM T cells showed impaired CPT1A, upregulated FASN, and induced kidney injury. Conclusion: Our findings indicate that Th1 cells induced tubular cell injury through dysregulated metabolic reprogramming and autophagy, thereby indicating a new therapeutic approach for kidney tubular injury in T1DM.
MeSH term(s)	Autophagy ; Biomarkers/metabolism ; Diabetes Mellitus, Type 1/metabolism ; Humans ; Kidney/metabolism ; Kidney Tubules/metabolism ; Lipocalin-2 ; Pyruvate Dehydrogenase (Lipoamide) ; T-Lymphocytes
Chemical Substances	Biomarkers ; Lipocalin-2 ; PDHA2 protein, human (EC 1.2.4.1) ; Pyruvate Dehydrogenase (Lipoamide) (EC 1.2.4.1)
Language	English
Publishing date	2022-06-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgac378
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Article: Potential effects of allyl isothiocyanate on inhibiting cellular proliferation and inducing apoptotic pathway in human cisplatin-resistant oral cancer cells.

Chang, Pei-Ying / Tsai, Fuu-Jen / Bau, Da-Tian / Hsu, Yuan-Man / Yang, Jai-Sing / Tu, Ming-Gene / Chiang, Shang-Lun

Journal of the Formosan Medical Association = Taiwan yi zhi

2020 Volume 120, Issue 1 Pt 2, Page(s) 515–523

Abstract: Background/purpose: Cisplatin-resistant oral cancer is clinically difficult to manage and the dose-dependent toxicities of cisplatin has been widely concerned. Allyl isothiocyanate (AITC), known as mustard oil, is a plant-derived compound abundant in ... ...

Abstract	Background/purpose: Cisplatin-resistant oral cancer is clinically difficult to manage and the dose-dependent toxicities of cisplatin has been widely concerned. Allyl isothiocyanate (AITC), known as mustard oil, is a plant-derived compound abundant in cruciferous vegetables. It is reported to have anti-cancer potential as a natural dietary chemopreventive compound against a variety of cancers, but the effect of AITC on cisplatin-resistant cancer cells is still little-known. Methods: Human CAL27-cisplatin-resistant oral cancer cells (CAR cells) were examined to investigate the antitumor properties of AITC. 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay, IncuCyte™ S3 cell proliferation assay, 4',6-diamidino-2-phenylindole (DAPI) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining as well as Western blot analysis were deployed. Results: AITC decreased CAR cell viability, induced cell death of CAR cells and inhibited the confluences of cultured CAR cells. When CAR cells were treated with AITC, activation of caspase-3 and caspase-9 by AITC was observed and could be reversed by Z-VAD-fmk (pan-caspase inhibitor). Furthermore, the protein expressions of phosphorylated protein kinase B (p-AKT) and phosphorylated mammalian target of rapamycin (p-mTOR) were suppressed in AITC-treated CAR cells, whereas protein expressions of Bax, cytochrome c, Apaf-1, cleaved caspase-3, and cleaved caspase-9 were upregulated in AITC-treated CAR cells. Conclusion: AITC can inhibit Akt/mTOR proliferation signaling and promote mitochondria-dependent apoptotic pathway through AITC-enhanced activities of caspase-3 and caspase-9 in CAR cells.
MeSH term(s)	Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Cisplatin/pharmacology ; Drug Resistance, Neoplasm ; Humans ; Isothiocyanates ; Mouth Neoplasms/drug therapy
Chemical Substances	Isothiocyanates ; allyl isothiocyanate (BN34FX42G3) ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2020-07-03
Publishing country	Singapore
Document type	Journal Article
ZDB-ID	2096659-3
ISSN	1876-0821 ; 0929-6646
ISSN (online)	1876-0821
ISSN	0929-6646
DOI	10.1016/j.jfma.2020.06.025
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Article ; Online: MCP-1/MCPIP-1 Signaling Modulates the Effects of IL-1β in Renal Cell Carcinoma through ER Stress-Mediated Apoptosis.

Lee, Chia-Huei / Hung, Pin-Feng / Lu, Shang-Chieh / Chung, Hsuan-Lien / Chiang, Shang-Lun / Wu, Chun-Te / Chou, Wei-Chun / Sun, Chiao-Yin

International journal of molecular sciences

2019 Volume 20, Issue 23

Abstract: In renal cell carcinoma (RCC), interleukin (IL)-1β may be a pro-metastatic cytokine. However, we have not yet noted the clinical association between tumoral expression or serum level of IL-1β and RCC in our patient cohort. Herein, we investigate ... ...

Abstract	In renal cell carcinoma (RCC), interleukin (IL)-1β may be a pro-metastatic cytokine. However, we have not yet noted the clinical association between tumoral expression or serum level of IL-1β and RCC in our patient cohort. Herein, we investigate molecular mechanisms elicited by IL-1β in RCC. We found that IL-1β stimulates substantial monocyte chemoattractant protein (MCP)-1 production in RCC cells by activating NF-kB and AP-1. In our xenograft RCC model, intra-tumoral MCP-1 injection down-regulated Ki67 expression and reduced tumor size. Microarray analysis revealed that MCP-1 treatment altered protein-folding processes in RCC cells. MCP-1-treated RCC cells and xenograft tumors expressed MCP-1-induced protein (MCPIP) and molecules involved in endoplasmic reticulum (ER) stress-mediated apoptosis, namely C/EBP Homologous Protein (CHOP), protein kinase-like ER kinase (PERK), and calnexin (CNX). ER stress-mediated apoptosis in MCP-1-treated RCC cells was confirmed using Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) assay. Moreover, ectopic MCPIP expression increased PERK expression in Human embryonic kidney (HEK)293 cells. Our meta-analysis revealed that low MCP-1 levels reduce 1-year post-nephrectomy survival in patients with RCC. Immunohistochemistry indicated that in some RCC biopsy samples, the correlation between MCP-1 or MCPIP expression and tumor stages was inverse. Thus, MCP-1 and MCPIP potentially reduce the IL-1β-mediated oncogenic effect in RCC; our findings suggest that ER stress is a potential RCC treatment target.
MeSH term(s)	Animals ; Apoptosis ; Carcinoma, Renal Cell/blood ; Carcinoma, Renal Cell/genetics ; Carcinoma, Renal Cell/metabolism ; Carcinoma, Renal Cell/pathology ; Cell Line, Tumor ; Chemokine CCL2/genetics ; Chemokine CCL2/metabolism ; Endoplasmic Reticulum Stress ; Gene Expression Regulation, Neoplastic ; Humans ; Interleukin-1beta/blood ; Interleukin-1beta/metabolism ; Kidney Neoplasms/blood ; Kidney Neoplasms/genetics ; Kidney Neoplasms/metabolism ; Kidney Neoplasms/pathology ; Mice ; Neoplasm Proteins/metabolism ; Prognosis ; Protein Folding ; Ribonucleases/metabolism ; Signal Transduction ; Transcription Factors/metabolism ; Tumor Burden ; Xenograft Model Antitumor Assays
Chemical Substances	Chemokine CCL2 ; IL1B protein, human ; Interleukin-1beta ; Neoplasm Proteins ; Transcription Factors ; Ribonucleases (EC 3.1.-) ; ZC3H12A protein, human (EC 3.1.-)
Language	English
Publishing date	2019-12-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms20236101
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Article ; Online: A haplotype-specific linkage disequilibrium pattern of monoamine oxidase A gene associated with regular smoking in women.

Chiang, Shang-Lun / Nithiyanantham, Srinivasan / Velmurugan, Bharath Kumar / Tu, Hung-Pin / Lee, Chien-Hung / Ko, Ying-Chin

The journal of gene medicine

2019 Volume 21, Issue 12, Page(s) e3142

Abstract: Background: Cigarette smoking in women is raising a public health problem. The X-linked monoamine oxidase A (MAOA) was considered as a susceptibility gene to substance abuse of tobacco, but the evolutionary effect of MAOA may lead to a positive or ... ...

Abstract	Background: Cigarette smoking in women is raising a public health problem. The X-linked monoamine oxidase A (MAOA) was considered as a susceptibility gene to substance abuse of tobacco, but the evolutionary effect of MAOA may lead to a positive or negative association between genetic variations and smoking development among study regions. Methods: Based on linkage disequilibrium (LD), we performed a haplotype-based association to explore the effect of MAOA gene on women's smoking risk in a case-control study. Results: Genotyped single nucleotide polymorphisms (SNPs) of MAOA gene, rs5953210G>A, rs2283725A>G and rs1137070T>C, were significantly associated with current smoking risk in women, and the increased level of plasma MAO-A activity was raised with per copy increment of risk allele in current smokers (P < .01). The haplotype patterns with minor haplotype frequency >.05 were constructed using the Expectation-Maximization algorithm, and the haplotype-specific A-G-C pattern raised the 2-fold risk to develop regular smoking (P = .0005). In the diplotype analysis based on X-inactivation mechanism relative to no and full dosage compensation, we showed that A-G-C haplotype not only increased regular smoking risk in a dose-dependent manner (P Conclusion: This study provides information on MAOA LD-based haplotype and diplotype patterns in women smoking.
MeSH term(s)	Adult ; Age Factors ; Aged ; Alleles ; Enzyme Activation ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Linkage Disequilibrium ; Middle Aged ; Monoamine Oxidase/genetics ; Monoamine Oxidase/metabolism ; Odds Ratio ; Polymorphism, Single Nucleotide ; Smoking/genetics
Chemical Substances	Monoamine Oxidase (EC 1.4.3.4)
Language	English
Publishing date	2019-12-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1458024-x
ISSN	1521-2254 ; 1099-498X
ISSN (online)	1521-2254
ISSN	1099-498X
DOI	10.1002/jgm.3142
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Zs.A 5423: Show issues

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Article ; Online: Long, Noncoding RNA SRA Induces Apoptosis of β-Cells by Promoting the IRAK1/LDHA/Lactate Pathway.

Huang, Yu-Nan / Chiang, Shang-Lun / Lin, Yu-Jung / Liu, Su-Ching / Li, Yen-Hsien / Liao, Yu-Chen / Lee, Maw-Rong / Su, Pen-Hua / Tsai, Fuu-Jen / Hung, Hui-Chih / Wang, Chung-Hsing

International journal of molecular sciences

2021 Volume 22, Issue 4

Abstract: Long non-coding RNA steroid receptor RNA activators (LncRNA SRAs) are implicated in the β-cell destruction of Type 1 diabetes mellitus (T1D), but functional association remains poorly understood. Here, we aimed to verify the role of LncRNA SRA regulation ...

Abstract	Long non-coding RNA steroid receptor RNA activators (LncRNA SRAs) are implicated in the β-cell destruction of Type 1 diabetes mellitus (T1D), but functional association remains poorly understood. Here, we aimed to verify the role of LncRNA SRA regulation in β-cells. LncRNA SRAs were highly expressed in plasma samples and peripheral blood mononuclear cells (PBMCs) from T1D patients. LncRNA SRA was strongly upregulated by high-glucose treatment. LncRNA SRA acts as a microRNA (miR)-146b sponge through direct sequence-structure interactions. Silencing of lncRNA SRA increased the functional genes of Tregs, resulting in metabolic reprogramming, such as decreased lactate levels, repressed lactate dehydrogenase A (LDHA)/phosphorylated LDHA (pLDHA at Tyr10) expression, decreased reactive oxygen species (ROS) production, increased ATP production, and finally, decreased β-cell apoptosis in vitro. There was a positive association between lactate level and hemoglobin A1c (HbA1c) level in the plasma from patients with T1D. Recombinant human interleukin (IL)-2 treatment repressed lncRNA SRA expression and activity in β-cells. Higher levels of lncRNA-SRA/lactate in the plasma are associated with poor regulation in T1D patients. LncRNA SRA contributed to T1D pathogenesis through the inhibition of miR-146b in β-cells, with activating signaling transduction of interleukin-1 receptor-associated kinase 1 (IRAK1)/LDHA/pLDHA. Taken together, LncRNA SRA plays a critical role in the function of β-cells.
MeSH term(s)	Adolescent ; Antagomirs/pharmacology ; Apoptosis/drug effects ; Apoptosis/genetics ; Carrier Proteins/genetics ; Cell Line ; Diabetes Mellitus, Type 1/blood ; Diabetes Mellitus, Type 1/genetics ; Diabetes Mellitus, Type 1/pathology ; Feedback, Physiological/drug effects ; Female ; Gene Knockdown Techniques ; Glycated Hemoglobin A/analysis ; Humans ; Insulin-Secreting Cells/drug effects ; Insulin-Secreting Cells/pathology ; Interleukin-1 Receptor-Associated Kinases/metabolism ; L-Lactate Dehydrogenase/metabolism ; Lactic Acid/metabolism ; Male ; MicroRNAs/agonists ; MicroRNAs/antagonists & inhibitors ; MicroRNAs/genetics ; MicroRNAs/metabolism ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; Reactive Oxygen Species/metabolism ; Signal Transduction/drug effects ; Signal Transduction/genetics ; Transcriptional Activation/drug effects ; Up-Regulation/drug effects ; Young Adult
Chemical Substances	Antagomirs ; Carrier Proteins ; Glycated Hemoglobin A ; MIRN146 microRNA, human ; MicroRNAs ; RNA, Long Noncoding ; Reactive Oxygen Species ; hemoglobin A1c protein, human ; steroid receptor RNA activator, human ; Lactic Acid (33X04XA5AT) ; L-Lactate Dehydrogenase (EC 1.1.1.27) ; LDHA protein, human (EC 1.1.1.27) ; IRAK1 protein, human (EC 2.7.11.1) ; Interleukin-1 Receptor-Associated Kinases (EC 2.7.11.1)
Language	English
Publishing date	2021-02-09
Publishing country	Switzerland
Document type	Journal Article ; Observational Study
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22041720
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Article ; Online: Regulatory elements in vectors containing the ctEF-1α first intron and double enhancers for an efficient recombinant protein expression system.

Lee, Chi-Pin / Ko, Albert Min-Shan / Chiang, Shang-Lun / Lu, Chi-Yu / Tsai, Eing-Mei / Ko, Ying-Chin

Scientific reports

2018 Volume 8, Issue 1, Page(s) 15396

Abstract: To establish a stable and scalable transient protein production system, we modified the EF-1 first intron size and verified the order of two recombinant enhancers downstream of the SV40 polyA sequence. This new vector was named pHH-Gemini (pHH-GM1) and ... ...

Abstract	To establish a stable and scalable transient protein production system, we modified the EF-1 first intron size and verified the order of two recombinant enhancers downstream of the SV40 polyA sequence. This new vector was named pHH-Gemini (pHH-GM1) and was used to express alpha kinase 1 (ALPK1) and various other proteins, NLRP3, F-actin, Camodulin, PP2A, URAT1, Rab11a and myosin IIA. The results showed that, compared with six commercial plasmids, pHH-GM1 significantly enhanced His-HA-ALPK1 expression in a western blot analysis of transfected HEK293T cells. The expression of various other genes was also successful using the pHH-GM1 vector. In addition, we inserted turbo green florescence protein (tGFP) into the pHH-GM1 vector, and an improvement in fluorescence intensity was observed after transient transfection of HEK293T cells. For large-scale production, protein production was tested by standard supplementation with one volume of medium, and volumetric yields of 2 and 2.3 mg/L were achieved with pHH-GM1-ALPK1 in HEK293-F and CHO-S cells, respectively. We found that cell viability was more than 70% 11 days after cells were transfected with the pHH-GM1 vector. The pHH-GM1 vector with the ctEF-1α first intron and double enhancers, Simian virus 40 and Cytomegalovirus (SV40 and CMV) is an efficient CMV promoter-based gene expression system that can potentially be applied to study genes of interest and improve protein production.
MeSH term(s)	Animals ; CHO Cells ; Cricetinae ; Cricetulus ; Cytomegalovirus/genetics ; Enhancer Elements, Genetic/genetics ; Gene Expression ; Genetic Vectors/genetics ; Green Fluorescent Proteins/chemistry ; Green Fluorescent Proteins/genetics ; HEK293 Cells ; Humans ; Introns/genetics ; Peptide Elongation Factor 1/chemistry ; Peptide Elongation Factor 1/genetics ; Plasmids/chemistry ; Protein Domains/genetics ; Recombinant Fusion Proteins/chemistry ; Recombinant Fusion Proteins/genetics ; Regulatory Sequences, Nucleic Acid/genetics ; Transfection/methods
Chemical Substances	Peptide Elongation Factor 1 ; Recombinant Fusion Proteins ; Green Fluorescent Proteins (147336-22-9)
Language	English
Publishing date	2018-10-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-018-33500-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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