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Article: Pregnancy Zone Protein as an Emerging Biomarker for Cardiovascular Risk in Pediatric Chronic Kidney Disease.

Chen, Wei-Ling / Liao, Wei-Ting / Hsu, Chien-Ning / Tain, You-Lin

2023 Volume 12, Issue 18

Abstract: Cardiovascular disease (CVD) is a significant cause of mortality and morbidity among children with chronic kidney disease (CKD). The causes of pediatric CKD differ from those in adults, as congenital anomalies in the kidney and urinary tract (CAKUT) are ... ...

Abstract	Cardiovascular disease (CVD) is a significant cause of mortality and morbidity among children with chronic kidney disease (CKD). The causes of pediatric CKD differ from those in adults, as congenital anomalies in the kidney and urinary tract (CAKUT) are the leading causes in childhood. Identifying ideal markers of CVD risk early is crucial for CKD children to improve their care. Previously, we screened differentially expressed proteins in CKD children with or without blood pressure (BP) abnormalities and identified pregnancy zone protein (PZP). In 106 children and adolescents with CKD stages G1-G4, we analyzed plasma PZP concentration. The associations between PZP and ambulatory BP monitoring (ABPM) profile, parameters of cardiac and carotid ultrasounds, indices of arterial stiffness, and nitric oxide (NO) parameters were determined. We observed that PZP positively correlated with arterial stiffness indices, beta index, and pulse wave velocity in CAKUT. CKD children with abnormalities in ABPM and night dipping displayed a higher PZP concentration than those without. Additionally, the PZP level was positively correlated with NO bioavailability. In conclusion, our results suggest PZP has differential influences on cardiovascular risk in CAKUT and non-CAKUT children. Identification of this relationship is novel in the pediatric CKD literature.
Language	English
Publishing date	2023-09-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12185894
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Complement Factor H and Related Proteins as Markers of Cardiovascular Risk in Pediatric Chronic Kidney Disease.

Liao, Wei-Ting / Chen, Wei-Ling / Tain, You-Lin / Hsu, Chien-Ning

Biomedicines

2022 Volume 10, Issue 6

Abstract: Cardiovascular disease (CVD) is the main cause of mortality among chronic kidney disease (CKD) patients, both in adults and in children. Hypertension is one of the risk factors of CVD. For early detection of subclinical CVD in pediatric CKD, 24 h ... ...

Abstract	Cardiovascular disease (CVD) is the main cause of mortality among chronic kidney disease (CKD) patients, both in adults and in children. Hypertension is one of the risk factors of CVD. For early detection of subclinical CVD in pediatric CKD, 24 h ambulatory blood pressure monitoring (ABPM), cardiosonography, and arterial stiffness assessment were evaluated. CAKUT (congenital anomalies of the kidney and urinary tract) are the main etiologies of pediatric CKD. Previously, by a proteomic approach, we identified complement factor H (CFH) and related proteins differentially expressed between children with CAKUT and non-CAKUT CKD. In this study, we aimed to evaluate whether CFH, CFH-related protein-2 (CFHR2), and CFH-related protein-3 (CFHR3) were related to CVD risk in children with CKD. This study included 102 subjects aged 6 to 18 years old. The non-CAKUT group had higher plasma CFHR3 levels than the CAKUT group (p = 0.046). CFHR3 was negatively correlated with LV mass (p = 0.009). CFHR2 was higher in children with CKD with 24 h hypertension in the ABPM profile (p < 0.05). In addition, children with non-CAKUT CKD with day-time hypertension (p = 0.036) and increased BP load (p = 0.018) displayed a lower plasma CFHR3 level. Our results highlight that CFH and related proteins play a role for CVD in children with CKD. Early assessment of CFH, CFHR2, and CFHR3 may have clinical utility in discriminating CV risk in children with CKD with different etiologies.
Language	English
Publishing date	2022-06-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10061396
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Article ; Online: Correction: CBAP regulates the function of Akt-associated TSC protein complexes to modulate mTORC1 signaling.

Liao, Wei-Ting / Chiang, Yun-Jung / Yang-Yen, Hsin-Fang / Hsu, Li-Chung / Chang, Zee-Fen / Yen, Jeffrey J Y

The Journal of biological chemistry

2024 Volume 300, Issue 2, Page(s) 105686

Language	English
Publishing date	2024-01-29
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2024.105686
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Article: Indocyanine-Green-Loaded Liposomes for Photodynamic and Photothermal Therapies: Inducing Apoptosis and Ferroptosis in Cancer Cells with Implications beyond Oral Cancer.

Liao, Wei-Ting / Chang, Dao-Ming / Lin, Meng-Xian / Lee, Jeng-Woei / Tung, Yi-Chung / Hsiao, Jong-Kai

Pharmaceutics

2024 Volume 16, Issue 2

Abstract: Oral cancer represents a global health burden, necessitating novel therapeutic strategies. Photodynamic and photothermal therapies using indocyanine green (ICG) have shown promise due to their distinctive near-infrared (NIR) light absorption ... ...

Abstract	Oral cancer represents a global health burden, necessitating novel therapeutic strategies. Photodynamic and photothermal therapies using indocyanine green (ICG) have shown promise due to their distinctive near-infrared (NIR) light absorption characteristics and FDA-approved safety profiles. This study develops ICG-loaded liposomes (Lipo-ICGs) to further explore their potential in oral cancer treatments. We synthesized and characterized the Lipo-ICGs, conducted in vitro cell culture experiments to assess cellular uptake and photodynamic/photothermal effects, and performed in vivo animal studies to evaluate their therapeutic efficacy. Quantitative cell apoptosis and gene expression variation were further characterized using flow cytometry and RNA sequencing, respectively. Lipo-ICGs demonstrated a uniform molecular weight distribution among particles. The in vitro studies showed a successful internalization of Lipo-ICGs into the cells and a significant photodynamic treatment effect. The in vivo studies confirmed the efficient delivery of Lipo-ICGs to tumor sites and successful tumor growth inhibition following photodynamic therapy. Moreover, light exposure induced a time-sensitive photothermal effect, facilitating the further release of ICG, and enhancing the treatment efficacy. RNA sequencing data showed significant changes in gene expression patterns upon Lipo-ICG treatment, suggesting the activation of apoptosis and ferroptosis pathways. The findings demonstrate the potential of Lipo-ICGs as a therapeutic tool for oral cancer management, potentially extending to other cancer types.
Language	English
Publishing date	2024-02-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics16020224
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Article ; Online: Pathophysiology of Inflammatory Bowel Diseases.

Chen, Chung-Jen / Hu, Huangming / Liao, Wei-Ting

The New England journal of medicine

2021 Volume 384, Issue 14, Page(s) 1376–1377

MeSH term(s)	Humans ; Inflammatory Bowel Diseases
Language	English
Publishing date	2021-04-07
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMc2101562
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Article: TSLP regulates mitochondrial ROS-induced mitophagy via histone modification in human monocytes.

Lin, Yi-Ching / Lin, Yu-Chih / Tsai, Mei-Lan / Liao, Wei-Ting / Hung, Chih-Hsing

Cell & bioscience

2022 Volume 12, Issue 1, Page(s) 32

Abstract: Background: Thymic stromal lymphopoietin (TSLP) is a Th2-like cytokine involved in asthma pathogenesis. Excessive reactive oxygen species (ROS) production can lead to airway inflammation, hyperresponsiveness and remodeling. Mitophagy, followed by ROS ... ...

Abstract	Background: Thymic stromal lymphopoietin (TSLP) is a Th2-like cytokine involved in asthma pathogenesis. Excessive reactive oxygen species (ROS) production can lead to airway inflammation, hyperresponsiveness and remodeling. Mitophagy, followed by ROS production, is the selective degradation of mitochondria by autophagy and often occurs in defective mitochondria. In the present study, we aimed to examine the effects of TSLP on ROS production and mitophagy in human monocytes and to investigate the underlying mechanisms, including epigenetic regulation. Results: TSLP induced ROS generation, and the effects were reversed by the antioxidant N-acetylcysteine (NAC) in THP-1 cells. Transmission electron microscopy images showed donut-shaped mitochondria that lost the cristae ultrastructure after TSLP stimulation. A decrease in mitochondrial membrane potential, decreased MTCO2 expression, and increased mitochondrial DNA release after TSLP stimulation were found. TSLP enhanced mitochondrial complex I and complex II/III activity and increased mitochondrial copy numbers and the expression of the complex II SHDA gene. TSLP-induced SHDA expression was inhibited by the histone acetyltransferase inhibitor anacardic acid (AA) and the histone methyltransferase inhibitor methylthioadenosine (MTA), and chromatin immunoprecipitation assays revealed that TSLP enhanced H3 acetylation, H4 acetylation, and H3K4 and H3K36 trimethylation in the SHDA promoter. Confocal laser microscopy showed that TSLP treatment increased the signals of the mitophagy-related proteins PINK1, LC3, phospho-parkin and phospho-ubiquitin, and pretreatment with AA and MTA reduced TSLP-induced PINK1 and LC3 accumulation in mitochondria. Western blot analysis showed that TSLP significantly increased phosphor-AMPK signal intensity, and the effects were inhibited by the antioxidant NAC. The increased signal intensities of the mitophagy-related proteins PINK1, Parkin and LC3 I/II were decreased by dorsomorphin, an AMPK inhibitor. TSLP decreased M1-related cytokine CXCL-10 production and increased M2-related cytokine CCL-1 and CCL-22 production, which was suppressed by the mitophagy inhibitor Mdivi-1 and PINK1 gene knockdown. Conclusions: Epithelial-derived TSLP regulates ROS production and mitophagy through AMPK activation and histone modification and alters M1/M2 chemokine expression in human monocytes.
Language	English
Publishing date	2022-03-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2593367-X
ISSN	2045-3701
ISSN	2045-3701
DOI	10.1186/s13578-022-00767-w
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Article ; Online: CBAP regulates the function of Akt-associated TSC protein complexes to modulate mTORC1 signaling.

Liao, Wei-Ting / Chiang, Yun-Jung / Yang-Yen, Hsin-Fang / Hsu, Li-Chung / Chang, Zee-Fen / Yen, Jeffrey J Y

The Journal of biological chemistry

2023 Volume 299, Issue 12, Page(s) 105455

Abstract: The Akt-Rheb-mTORC1 pathway plays a crucial role in regulating cell growth, but the mechanisms underlying the activation of Rheb-mTORC1 by Akt remain unclear. In our previous study, we found that CBAP was highly expressed in human T-ALL cells and primary ...

Abstract	The Akt-Rheb-mTORC1 pathway plays a crucial role in regulating cell growth, but the mechanisms underlying the activation of Rheb-mTORC1 by Akt remain unclear. In our previous study, we found that CBAP was highly expressed in human T-ALL cells and primary tumors, and its deficiency led to reduced phosphorylation of TSC2/S6K1 signaling proteins as well as impaired cell proliferation and leukemogenicity. We also demonstrated that CBAP was required for Akt-mediated TSC2 phosphorylation in vitro. In response to insulin, CBAP was also necessary for the phosphorylation of TSC2/S6K1 and the dissociation of TSC2 from the lysosomal membrane. Here we report that CBAP interacts with AKT and TSC2, and knockout of CBAP or serum starvation leads to an increase in TSC1 in the Akt/TSC2 immunoprecipitation complexes. Lysosomal-anchored CBAP was found to override serum starvation and promote S6K1 and 4EBP1 phosphorylation and c-Myc expression in a TSC2-dependent manner. Additionally, recombinant CBAP inhibited the GAP activity of TSC2 complexes in vitro, leading to increased Rheb-GTP loading, likely due to the competition between TSC1 and CBAP for binding to the HBD domain of TSC2. Overexpression of the N26 region of CBAP, which is crucial for binding to TSC2, resulted in a decrease in mTORC1 signaling and an increase in TSC1 association with the TSC2/AKT complex, ultimately leading to increased GAP activity toward Rheb and impaired cell proliferation. Thus, we propose that CBAP can modulate the stability of TSC1-TSC2 as well as promote the translocation of TSC1/TSC2 complexes away from lysosomes to regulate Rheb-mTORC1 signaling.
MeSH term(s)	Humans ; Cell Proliferation ; Guanosine Triphosphate/metabolism ; Immunoprecipitation ; Lysosomes/metabolism ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Membrane Proteins/deficiency ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Ras Homolog Enriched in Brain Protein/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Tuberous Sclerosis Complex 1 Protein/metabolism ; Tuberous Sclerosis Complex 2 Protein/metabolism
Chemical Substances	Guanosine Triphosphate (86-01-1) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Membrane Proteins ; MYC protein, human ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Ras Homolog Enriched in Brain Protein ; RHEB protein, human ; ribosomal protein S6 kinase, 70kD, polypeptide 1 (EC 2.7.11.1) ; TMEM102 protein, human ; TOR Serine-Threonine Kinases (EC 2.7.11.1) ; TSC1 protein, human ; TSC2 protein, human ; Tuberous Sclerosis Complex 1 Protein ; Tuberous Sclerosis Complex 2 Protein
Language	English
Publishing date	2023-11-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2023.105455
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Article: Plasma and Urinary Platelet Factor 4 as Biomarkers for Cardiovascular Risk in Children with Chronic Kidney Disease.

Hsu, Chien-Ning / Liao, Wei-Ting / Chen, Wei-Ling / Chang-Chien, Guo-Ping / Lin, Sufan / Tain, You-Lin

Biomedicines

2023 Volume 11, Issue 12

Abstract: Children suffering from chronic kidney disease (CKD) have a high risk of cardiovascular disease (CVD). The early detection and diagnosis of subclinical CVD in pediatric CKD can reduce mortality later in life. Plasma factor 4 (PF4) is a chemokine released ...

Abstract	Children suffering from chronic kidney disease (CKD) have a high risk of cardiovascular disease (CVD). The early detection and diagnosis of subclinical CVD in pediatric CKD can reduce mortality later in life. Plasma factor 4 (PF4) is a chemokine released by activated platelets. We examined whether or not PF4 in the plasma and urine, its kidney function normalized ratio, and fractional excretion have differential associations with CVD risk markers in 139 youths aged 3 to 18 years old with CKD stages G1-G4. Significant negative correlations were observed between plasma PF4 and cardiovascular surrogate markers, such as the left ventricular mass index (LVMI), carotid intima-media thickness (cIMT), and pulse wave velocity (PWV). The plasma PF4/creatinine (Cr) ratio was lower in CKD children with a high daytime BP and 24 h BP, high BP load, and nocturnal non-dipping status. After adjusting for confounders, the plasma PF4 and plasma PF4/Cr ratio still independently predicted an abnormal ABPM profile. In addition, both the plasma PF4 and plasma PF4/Cr ratio presented a negative correlation with the L-arginine and asymmetric dimethylarginine ratio. These findings provide convincing evidence supporting the link between PF4 and CVD markers in pediatric CKD. Our study highlights the importance of further research to assess the performance of PF4-related biomarkers in predicting CVD events and CKD progression in children with CKD.
Language	English
Publishing date	2023-12-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11123318
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Article: The Role of Exosomes in Pancreatic Ductal Adenocarcinoma Progression and Their Potential as Biomarkers.

Hsu, Sheng-Kai / Jadhao, Mahendra / Liao, Wei-Ting / Chang, Wen-Tsan / Lin, I-Ling / Chiu, Chien-Chih

Cancers

2023 Volume 15, Issue 6

Abstract: Pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic malignancy, is an aggressive and lethal cancer with a dismal five-year survival rate. Despite remarkable improvements in cancer therapeutics, the clinical outcome of PDAC patients ... ...

Abstract	Pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic malignancy, is an aggressive and lethal cancer with a dismal five-year survival rate. Despite remarkable improvements in cancer therapeutics, the clinical outcome of PDAC patients remains poor due to late diagnosis of the disease. This highlights the importance of early detection, wherein biomarker evaluation including exosomes would be helpful. Exosomes, small extracellular vesicles (sEVs), are cell-secreted entities with diameters ranging from 50 to 150 nm that deliver cellular contents (e.g., proteins, lipids, and nucleic acids) from parent cells to regulate the cellular processes of targeted cells. Recently, an increasing number of studies have reported that exosomes serve as messengers to facilitate stromal-immune crosstalk within the PDAC tumor microenvironment (TME), and their contents are indicative of disease progression. Moreover, evidence suggests that exosomes with specific surface markers are capable of distinguishing patients with PDAC from healthy individuals. Detectable exosomes in bodily fluids (e.g., blood, urine, saliva, and pancreatic juice) are omnipresent and may serve as promising biomarkers for improving early detection and evaluating patient prognosis. In this review, we shed light on the involvement of exosomes and their cargos in processes related to disease progression, including chemoresistance, angiogenesis, invasion, metastasis, and immunomodulation, and their potential as prognostic markers. Furthermore, we highlight feasible clinical applications and the limitations of exosomes in liquid biopsies as tools for early diagnosis as well as disease monitoring. Taking advantage of exosomes to improve diagnostic capacity may provide hope for PDAC patients, although further investigation is urgently needed.
Language	English
Publishing date	2023-03-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15061776
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Article: Culprits of PDAC resistance to gemcitabine and immune checkpoint inhibitor: Tumour microenvironment components.

Hsu, Sheng-Kai / Jadhao, Mahendra / Liao, Wei-Ting / Chang, Wen-Tsan / Hung, Chun-Tzu / Chiu, Chien-Chih

Frontiers in molecular biosciences

2022 Volume 9, Page(s) 1020888

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal cancer with a dismal five-year survival rate of 11%. Despite remarkable advancements in cancer therapeutics, PDAC patients rarely benefit from it due to insurmountable treatment ... ...

Abstract	Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal cancer with a dismal five-year survival rate of 11%. Despite remarkable advancements in cancer therapeutics, PDAC patients rarely benefit from it due to insurmountable treatment resistance. Notably, PDAC is pathologically characterized by an extensive desmoplastic reaction and an extremely immunosuppressive tumour microenvironment (TME). The PDAC TME consists of cell components (e.g., tumour, immune and stromal cells) and noncellular components (e.g., extracellular matrix), exhibiting high complexity and their interplay resulting in resistance to chemotherapeutics and immune checkpoint inhibitors. In our review, we shed light on how crosstalk of complex environmental components modulates PDAC drug resistance, and we summarize related clinical trials. Moreover, we extend our discussion on TME exploration and exosome analysis, providing new insights into clinical applications, including personalized medicine, disease monitoring and drug carriers.
Language	English
Publishing date	2022-10-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2022.1020888
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