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Introduction
Niche regulation in stem cells, cancer reprogramming, and cell therapy
Additional affiliations
August 2016 - July 2017
April 2013 - present
Position
- Professor (Full)
February 2007 - March 2013
Position
- Professor (Associate)
Education
September 1994 - July 1997
Publications
Publications (109)
Sorafenib is the first approved systemic targeting agent for advanced HCC; however, when used alone, drug resistance can result in considerably reduced efficacy. Here, we demonstrate that niclosamide, an antihelminthic agent approved by the US Food and Drug Administration, can be repurposed to increase sorafenib sensitivity in sorafenib-resistant H...
Photothermal and photodynamic therapies (PTT/PDT) have been widely accepted as noninvasive therapeutic methods for cancer treatment. However, tumor hypoxia and insufficient delivery of photoactive compounds to cancer cells can reduce the efficacy of phototherapy. Herein, we first synthesized thiolated hyaluronic acid (THA) and then conjugated it wi...
Most cases of hepatocellular carcinoma (HCC) arise with the fibrotic microenvironment where hepatic stellate cells (HSCs) and carcinoma-associated fibroblasts (CAFs) are critical components in HCC progression. Therefore, CAF normalization could be a feasible therapy for HCC. Galectin-1 (Gal-1), a β-galactoside-binding lectin, is critical for HSC ac...
Background and Objectives
The novel coronavirus disease 2019 (COVID-19) has been a pandemic health issue in 30 January 2020. The mortality rate is as high as 50% in critically ill patients. Stem cell therapy is effective for those who are refractory to standard treatments. However, the immune responses that underlie stem cell therapy have not been...
Endoplasmic reticulum (ER) stress mediates the effects of obesity on aggravating sepsis-induced lung injury. We investigated whether exosomes from human placenta choriodecidual membrane-derived mesenchymal stem cells (pcMSCs) can mitigate pulmonary ER stress, lung injury, and the mechanisms of inflammation, oxidation, and apoptosis in lipopolysacch...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive upper and lower motor neuron (MN) degeneration with unclear pathology. The worldwide prevalence of ALS is approximately 4.42 per 100,000 populations, and death occurs within 3–5 years after diagnosis. However, no effective therapeutic modality for...
Obesity complicates sepsis and increases the mortality of sepsis. We examined the effects of exosomes (from human placenta choriodecidual membrane-derived mesenchymal stem cells, pcMSCs) on preventing sepsis in obesity and the mitigating role of hsa-let-7i-5p microRNA. Obese mice (adult male C57BL/6J mice fed a high-fat diet for 12 weeks) received...
Vitiligo is a chronic autoimmune depigmenting skin disorder characterized by patches of the skin losing functional melanocytes. Multiple combinatorial factors are involved in disease development, among which immune T cells play a prominent role. The immune cells implicated in melanocyte destruction through adaptive immunity include CD8 ⁺ cytotoxic...
Background:
The novel coronavirus disease 2019 (COVID-19) has been a global pandemic health issue since 30, January, 2020. Mortality rate was as high as more than 50% in critically ill patients. The Stem cell treatment is effective in refractory severe critically ill COVID-19 patients, but immune regulation mechanisms have not been reported well. T...
Breast cancer, a hormone‐dependent tumour, generally includes four molecular subtypes (luminal A, luminal B, HER2 enriched and triple‐negative) based on oestrogen receptor, progesterone receptor and human epidermal growth factor receptor‐2. Multiple hormones in the body regulate the development of breast cancer. Endocrine therapy is one of the prim...
The role of a YAP-IGF-1R signaling loop in HCC resistance to sorafenib remains unknown.
Method:
Sorafenib-resistant cells were generated by treating naïve cells (HepG2215 and Hep3B) with sorafenib. Different cancer cell lines from databases were analyzed through the ONCOMINE web server. BIOSTORM-LIHC patient tissues (46 nonresponders and 21 respo...
The mechanism on how extracellular matrix (ECM) cooperates with niche growth factors and oxygen tension to regulate the self-renewal of embryonic germline stem cells (GSCs) still remains unclear. Lacking of an appropriate in vitro cell model dramatically hinders the progress. Herein, using a serum-free culture system, we demonstrated that ECM lamin...
This study evaluated the biocompatibility and biological performance of novel additive-manufactured bioabsorbable iron-based porous suture anchors (iron_SAs). Two types of bioabsorbable iron_SAs, with double- and triple-helical structures (iron_SA_2_helix and iron_SA_3_helix, respectively), were compared with the synthetic polymer-based bioabsorbab...
Background
Small blood stem cells (SB cells), isolated from human peripheral blood, demonstrated the ability to benefit bone regeneration and osseointegration. The primary goal of our study is to examine the safety and tolerability of SB cells in dental implantation for human patients with severe bone defects.
Methods
Nine patients were enrolled a...
Background:
Animals develop skin regional specificities to best adapt to their environments. Birds are excellent models in which to study the epigenetic mechanisms that facilitate these adaptions. Patients suffering from SATB2 mutations exhibit multiple defects including ectodermal dysplasia-like changes. The preferential expression of SATB2, a ch...
Hereditary anemia has various manifestations, such as sickle cell disease (SCD), Fanconi anemia, glucose-6-phosphate dehydrogenase deficiency (G6PDD), and thalassemia. The available management strategies for these disorders are still unsatisfactory and do not eliminate the main causes. As genetic aberrations are the main causes of all forms of here...
Mesenchymal stem/stromal cells (MSCs) are a promising resource for cell-based therapy because of their high immunomodulation ability, tropism towards inflamed and injured tissues, and their easy access and isolation. Currently, there are more than 1200 registered MSC clinical trials globally. However, a lack of standardized methods to characterize...
Insulin-like Growth Factor (IGF)/IGF-1 Receptor (IGF-1R) signaling is known to regulate stem cell pluripotency and differentiation to trigger cell proliferation, organ development, and tissue regeneration during embryonic development. Unbalanced IGF/IGF-1R signaling can promote cancer cell proliferation and activate cancer reprogramming in tumor ti...
The use of immune checkpoint inhibitors (ICI) in treating cancer has revolutionized the approach to eradicate cancer cells by reactivating immune responses. However, only a subset of patients benefits from this treatment; the majority remains unresponsive or develops resistance to ICI therapy. Increasing evidence suggests that metabolic machinery i...
Stem cells work with their niches harmoniously during development. This concept has been extended to cancer pathology for cancer stem cells (CSCs) or cancer reprogramming. IGF-1R, a classical survival signaling, has been shown to regulate stem cell pluripotency, CSCs, or cancer reprogramming. The mechanism underlying such cell fate determination is...
In the original publication of this article [1], labelling within Fig. 7a was incorrect. The updated figure is shown below, with 'DMT1' now corrected to read 'DNMT1'.
Current guidelines recommend antibiotic prophylaxis for all patients with various degrees of cirrhosis and upper gastrointestinal (UGI) bleeding. This study assessed the need for antibiotic prophylaxis in patients with low Child–Pugh scores. We retrospectively screened all patients with cirrhosis who underwent upper endoscopies for UGI bleeding in...
Background:
The inflammatory cytokine interleukin-6 (IL-6) is critical for the expression of octamer-binding transcription factor 4 (OCT4), which is highly associated with early tumor recurrence and poor prognosis of hepatocellular carcinomas (HCC). DNA methyltransferase (DNMT) family is closely linked with OCT4 expression and drug resistance. How...
Gastrointestinal (GI) cancer is one of the common causes of cancer-related death worldwide. Chemotherapy and/or immunotherapy are the current treatments, but some patients do not derive clinical benefits. Recently, studies from cancer molecular subtyping have revealed that tumor molecular biomarkers may predict the immunotherapeutic response of GI...
Triple-negative breast cancer (TNBC) is cancer that tested as negative for estrogen receptors (ER), progesterone receptors (PR), and excess human epidermal growth factor receptor 2 (HER2) protein which accounts for 15%–20% of all breast cancer cases. TNBC is considered to be a poorer prognosis than other types of breast cancer, mainly because it in...
BACKGROUND
Pooled human platelet lysate (HPL) can replace fetal bovine serum (FBS) as xeno‐free supplement for ex vivo expansion of mesenchymal stromal cells (MSCs). We evaluate here whether a double‐virally‐inactivated HPL (DVI‐HPL) prepared from expired Intercept‐treated platelet concentrates (PCs) and treated by solvent/detergent (S/D) can be us...
Endometriosis is an estrogen-dependent inflammatory disease that affects up to 10% of women of reproductive age and accounts for up to 50% of female infertility cases. It has been highly associated with poorer outcomes of assisted reproductive technology (ART), including decreased oocyte retrieval, lower implantation, and pregnancy rates. A better...
Single-stranded DNA-binding proteins (SSBs) are essential to cells as they participate in DNA metabolic processes, such as DNA replication, repair, and recombination. The functions of SSBs have been studied extensively in Escherichia coli. Unlike E. coli, which contains only one type of SSB (EcSSB), some bacteria have more than one paralogous SSB....
p>Purpose: To assess the potential therapeutic target on the alpha 9 nicotinic acetylcholine receptor (α9-nAChR) and the insulin-like growth factor (IGF)-I receptor (IGF-IR) for preventing distant metastasis in TNBC patients. Experimental Design: Expression levels of stemness-related genes, α9-nAChR and IGF-IR in clinical tissues (n = 67) were anal...
Purpose: Chronic hepatic inflammatory cytokine interleukin 6 (IL-6) appears important role in pluripotent transcription factor OCT4 expression particularly in HBV-related hepatocellular carcinomas (HBV-HCC). However, the underlying mechanism still remains largely unknown. Experimental Design: Serum levels of IL-6 were detected using ELISA assays (n...
Purpose: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is the leading cause of cancer mortality worldwide. To date, Sorafenib remains the standard of care for advanced HCCs not amenable to curative therapies such as surgery or local ablation. Unfortunately, clinical efficacy of Sorafenib remains marginal as most HCC pat...
Hypoxia cooperates with endocrine signaling to maintain the symmetric self-renewal proliferation and migration of embryonic germline stem cells (GSCs). However, the lack of an appropriate in vitro cell model has dramatically hindered the understanding of the mechanism underlying this cooperation. Here, using a serum-free system, we demonstrated tha...
Purpose: To determine the role of insulin-like growth factor (IGF)-I receptor (IGF-IR) in alpha 9 nicotinic acetylcholine receptor (α9-nAChR)-induced stemness-related properties and to assess the therapeutic potential for preventing early tumor relapse and metastasis of TNBCs.
Experimental Design: Expression levels of stemness-related genes, α9-nAC...
[This corrects the article DOI: 10.1371/journal.pone.0149897.].
Tumor metastasis is the leading cause of death in cancer patients. Identifying metastatic biomarkers in tumor cells would help cancer diagnoses and the development of therapeutic targets. Yes-associated protein (YAP) plays an important role in organ development and has gained much attention in tumorigenesis. However, the role of YAP and the underly...
Hepatocellular carcinoma (HCC) is the sixth most common cancer, and the third leading cause of cancer mortality worldwide. Surgical resection can be curative for early stage HCC, but the risk of tumor recurrence remains high. Tumor stemness properties have been linked to early recurrence of HBV-related HCC (HBV-HCC), which continues to be a great c...
Production of tag-free SaDnaD proteins.
To obtain proteins without a His tag, tag-free SaDnaD, SaDnaDY176A, and SaDnaD1-195 proteins were produced using GST fusion and Factor Xa and were used in succeeding analysis. Coomassie Blue-stained SDS-PAGE (12%) of the purified SaDnaD (lane 1), GST-SaDnaD (lane 2), SaDnaD1-195 (lane 3), GST-SaDnaD1-195 (lan...
Protein purity.
Coomassie Blue-stained SDS-PAGE (12%) of the purified SaDnaD (lane 1), SaDnaD1-204 (lane 2), SaDnaD1-200 (lane 3), SaDnaD1-195 (lane 4) and molecular mass standards (M) are shown. The sizes of the standard proteins, from the top down, are as follows: 170, 130, 100, 70, 55, 40, 35, 25, 15, and 10 kDa.
(TIF)
ssDNA binding analysis of the deletion mutants of SaDnaD.
(A) SaDnaD1-195, (B) SaDnaD1-200, or (C) SaDnaD1-204, was incubated at 25°C for 30 min with 1.7 nM dT40 in a total volume of 10 μL in 20 mM Tris—HCl (pH 8.0) and 100 mM NaCl. The resulting samples were mixed with gel-loading solution (0.25% bromophenol blue and 40% sucrose; w/v), resolved on...
Residual plots for SPR fitting.
The estimated Kd values were derived by fitting the association and dissociation signals with a 1:1 (Langmuir) model using the Biacore T200 Evaluation Software. These residual plots were the calculated difference between the experimental and fitted data [57] for PriA—DnaD, PriA—DnaD1-204, PriA-DnaD1-200, DnaA—DnaD, a...
SaDnaD can significantly stimulate the ATPase activity of SaPriA but SaDnaD1-195 cannot.
SaPriA ATPase assay was performed with 0.4 mM [γ-32P] ATP, 0.125 μM of SaPriA, and 0.1 μM PS4/PS3-dT25 DNA substrate for 1 h. To study the effect, SaDnaD (10 μM) or SaDnaD1-195 (10 μM) was added into the assay solution. Aliquots (5 μL) were taken and spotted on...
SaDnaDY176A significantly stimulate the ATPase activity of SaPriA as SaDnaD did.
In this experiment, tag-free SaDnaD proteins were used for analysis of SaPriA ATPase activity. SaPriA ATPase assay was performed with 0.4 mM [γ-32P] ATP, 0.125 μM of SaPriA, and 0.1 μM PS4/PS3-dT25 DNA substrate for 1 h. To study the effect, SaDnaD (10 μM), SaDnaDY176A...
The expression of cancer stemness is believed to reduce the efficacy of current therapies against hepatocellular carcinoma (HCC). Understanding of the stemness-regulating signaling pathways incurred by a specific etiology can facilitate the development of novel targets for individualized therapy against HCC. Niche environments, such as virus-induce...
Effects of inflamed-CM dilution on mRNA levels of POU5F1 (OCT4), NANOG, and IGF-IR in HepG2.2.15 and Hep3B cells.
(PDF)
Correlations of the levels of MCP-1/CD68 and pluripotent transcription factors OCT4 and NANOG in HBV-HCC or HBV-negative HCC tissues.
(PDF)
Real-time quantitative PCR primer and product size.
(PDF)
Transforming growth factor (TGF-β)/TGF-β receptor signal is known to promote cell migration. Up-regulation of TGF-β in serum/peritoneal fluid and increased levels of pluripotent transcription factor OCT4 in endometriotic tissues are frequently observed in patients with endometriosis. However, the mechanisms underlying how TGF-β/TGF-β receptor and O...
Effects of OCT4 on TGF-βI-induced mRNA expression levels of OCT4, N-CAD, and SNAIL in human endometrial RL95-2 and HEC1A cell lines.
Quantitative real-time PCR analysis was independently repeated at least 3 times. The relative mRNA expression folds of OCT4, N-CAD, and SNAIL in TGF-βI-treated human endometrial RL95-2 and HEC1A cells with or without...
Description of the study population.
(PDF)
Positive correlations between the expression of TGF-β RII and OCT4 in human endometriotic tissues.
The transcriptional levels (ΔCt of gene levels/β2-microglobulin) of OCT4 were compared with those of the TGF-β RII using the Pearson correlation analysis to determine the statistical correlations.
(TIFF)
Effects of TGF-β and shRNA on cell-proliferation in primary endometriotic stromal cells.
The viability of human endometriotic stromal cells with or without shRNA and/or TGF-β (1 ng/ml) treatment for 24h was evaluated using a WST-1 assay. The cell viability at 24h is represented with folds when compare to that at 0 h incubation time. Three independe...
Real-time quantitative PCR primer and product size.
(PDF)
The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastr...
Purpose: To unravel the role of inflammatory cytokine IL-6 and IGF-1 receptor (IGF-1R) in expressing stemness-related properties and to evaluate the prognostic values of pluripotent transcription factor OCT4/NANOG, and IGF-1R in hepatocellular carcinoma (HCC).
Experimental Design: Frozen liver and HCC tissue samples were obtained from 191 patients...
Liver cirrhosis is a major risk factor for hepatocellular carcinoma (HCC), and all liver study societies recommend HCC surveillance in patients with cirrhosis. However, no ideal modality for HCC surveillance has been determined. The aim of this study is to assess the effectiveness of α-fetoprotein (AFP) measurement in HCC surveillance.
In this retr...
To unravel the role of interleukin (IL)-6 and insulin-like growth factor (IGF)-I receptor (IGFIR) in expressing stemness-related properties and to evaluate the prognostic values of pluripotent transcription factor OCT4/NANOG, and IGFIR in hepatocellular carcinoma (HCC).
Serum levels of IL6 were detected using ELISA assays (n = 120). The effects of...
Endometriosis is the eutopic and/or ectopic growth of endometrial tissues. High levels of TGF-β in peritoneal fluid and increased expression of OCT4 have been well documented in endometriosis. However, the molecular mechanism between TGF-β and OCT4 expression in endometriosis still remains largely unknown. In this study, we examined the roles of OC...
Background/purpose
The aim of this study was to investigate whether storage of extracted teeth in transportation solution for 24 hours has a negative effect on the cell density and mechanical properties of thawed pulp tissue extracted from frozen intact teeth.
Material and methods
Human premolars were kept in transportation solution for 0 hours or...
Single-stranded DNA-binding protein (SSB) plays an important role in DNA metabolism, including DNA replication, repair, and recombination, and is therefore essential for cell survival. Bacterial SSB consists of an N-terminal ssDNA-binding/oligomerization domain and a flexible C-terminal protein-protein interaction domain. We characterized the ssDNA...
Replication restart primosome is a complex dynamic system that is essential for bacterial survival. This system uses various proteins to reinitiate chromosomal DNA replication to maintain genetic integrity after DNA damage. The replication restart primosome in
Escherichia coli
is composed of PriA helicase, PriB, PriC, DnaT, DnaC, DnaB helicase, and...
The ability of adult stem cells to reside in a quiescent state is crucial for preventing premature exhaustion of the stem cell pool. However, the intrinsic epigenetic factors that regulate spermatogonial stem cell quiescence are largely unknown. Here, we investigate in mice how DNA methyltransferase 3-like (DNMT3L), an epigenetic regulator importan...
Hypoxia inducible factor 2α (HIF-2α) is critical for primordial germ cell (PGC) survival as knockout of HIF-2α (HIF-2α−/−)