Heng Lin - Academia.edu (original) (raw)

Papers by Heng Lin

Research paper thumbnail of Multiplex detection of urinary miRNA biomarkers by transmission surface plasmon resonance

The Analyst, 2018

The clinical assessment of short-stranded nucleic acid biomarkers such as miRNAs could potentiall... more The clinical assessment of short-stranded nucleic acid biomarkers such as miRNAs could potentially provide useful information for monitoring disease progression, prompting definitive treatment decisions.

Research paper thumbnail of New Synthesized Activating Transcription Factor 3 Inducer SW20.1 Suppresses Resistin-Induced Metabolic Syndrome

Biomedicines

Obesity is an emerging concern globally with increasing prevalence. Obesity is associated with ma... more Obesity is an emerging concern globally with increasing prevalence. Obesity is associated with many diseases, such as cardiovascular disease, dyslipidemia, and cancer. Thus, effective new antiobesity drugs should be urgently developed. We synthesized SW20.1, a compound that induces activating transcription factor 3 (ATF3) expression. The results of Oil Red O staining and quantitative real-time polymerase chain reaction revealed that SW20.1 was more effective in reducing lipid accumulation in 3T3-L1 preadipocytes than the previously synthesized ST32db, and that it inhibited the expression of the genes involved in adipogenesis and lipogenesis. A chromatin immunoprecipitation assay indicated that SW20.1 inhibited adipogenesis and lipogenesis by binding to the upstream promoter region of resistin at two sites (−2861/−2854 and −241/−234). In mice, the intraperitoneal administration of SW20.1 reduced body weight, white adipocyte weight in different regions, serum cholesterol levels, adipo...

Research paper thumbnail of Emergent Roles of Circular RNAs in Metabolism and Metabolic Disorders

International Journal of Molecular Sciences, 2022

Circular RNAs (circRNAs) are an emerging group of long non-coding RNAs (lncRNAs) and have attract... more Circular RNAs (circRNAs) are an emerging group of long non-coding RNAs (lncRNAs) and have attracted attention again according to the progress in high-throughput sequencing in recent years. circRNAs are genome transcripts produced from pre-messenger (m)RNA regions in a specific process called “back-splicing,” which forms covalently closed continuous loops. Due to their lack of a 5’ cap and 3’ poly-adenylated tails, circRNAs are remarkably more stable than linear RNAs. Functionally, circRNAs can endogenously sponge to microRNAs, interact with RNA-binding proteins (RBPs), or translate themselves. Moreover, circRNAs can be expressed in cell type- or tissue-specific expression patterns. Therefore, they are proposed to play essential roles in fine-tuning our body’s homeostasis by regulating transcription and translation processes. Indeed, there has been accumulating emergent evidence showing that dysregulation of circRNAs can lead to metabolic disorders. This study explored the current kn...

Research paper thumbnail of ATF3-Mediated Epigenetic Regulation Protects against Acute Kidney Injury

Journal of the American Society of Nephrology, 2010

A variety of stress stimuli, including ischemia-reperfusion (I/R) injury, induce the transcriptio... more A variety of stress stimuli, including ischemia-reperfusion (I/R) injury, induce the transcriptional repressor ATF3 in the kidney. The functional consequences of this upregulation in ATF3 after renal I/R injury are not well understood. Here, we found that ATF3-deficient mice had higher renal I/R-induced mortality, kidney dysfunction, inflammation (number of infiltrating neutrophils, myeloperoxidase activity, and induction of IL-6 and P-selectin), and apoptosis compared with wild-type mice. Furthermore, gene transfer of ATF3 to the kidney rescued the renal I/R-induced injuries in the ATF3-deficient mice. Molecular and biochemical analysis revealed that ATF3 interacted directly with histone deacetylase 1 (HDAC1) and recruited HDAC1 into the ATF/NF-B sites in the IL-6 and IL-12b gene promoters. The ATF3-associated HDAC1 deacetylated histones, which resulted in the condensation of chromatin structure, interference of NF-B binding, and inhibition of inflammatory gene transcription after I/R injury. Taken together, these data demonstrate epigenetic regulation mediated by the stress-inducible gene ATF3 after renal I/R injury and suggest potential targeted approaches for acute kidney injury.

Research paper thumbnail of Abstract 275: Activating Transcription Factor 3 Protects Against Obesity and Metabolic Dysfunction Through Promoting Lipolysis and Adipocytes Browning

Circulation Research, 2017

Recent studies implying that promoting lipolysis or enhancing brown remodeling of white adipose t... more Recent studies implying that promoting lipolysis or enhancing brown remodeling of white adipose tissue is a potential strategy to treat obesity and metabolic syndrome. Activating transcription factor 3 (ATF3) is a member of the ATF/cAMP-response element binding protein family of transcriptional factors. It is upregulated under stress condition in a variety of tissues, including the adipocytes. However, the mechanism of ATF3 in adipocytes and obesity regulation are not clear. We gave high-fat-diet (HFD) to both ATF3-/- (KO) and their wild type littermates (WT) for 16 weeks. KO showed obvious obesity as compared to WT. The obese KO mice then received AAV8-mediated gene transfer of ATF3 (AAV8-ATF3) at 16 weeks, in which decrease body weights were observed as compared to KO receiving AAV8-GFP. Histology demonstrated increased adipocyte cell diameter in KO, in which such enlargement of adipocytes can be reversed by AAV8-ATF3 therapy. We then used ATF3-overexpressing 3T3-L1 preadipocytes ...

Research paper thumbnail of Adipocyte browning and resistance to obesity in mice is induced by expression of ATF3

Communications Biology, 2019

Billions of people have obesity-related metabolic syndromes such as diabetes and hyperlipidemia. ... more Billions of people have obesity-related metabolic syndromes such as diabetes and hyperlipidemia. Promoting the browning of white adipose tissue has been suggested as a potential strategy, but a drug still needs to be identified. Here, genetic deletion of activating transcription factor 3 (ATF3−/−) in mice under a high-fat diet (HFD) resulted in obesity and insulin resistance, which was abrogated by virus-mediated ATF3 restoration. ST32da, a synthetic ATF3 inducer isolated from Salvia miltiorrhiza, promoted ATF3 expression to downregulate adipokine genes and induce adipocyte browning by suppressing the carbohydrate-responsive element-binding protein–stearoyl-CoA desaturase-1 axis. Furthermore, ST32da increased white adipose tissue browning and reduced lipogenesis in HFD-induced obese mice. The anti-obesity efficacy of oral ST32da administration was similar to that of the clinical drug orlistat. Our study identified the ATF3 inducer ST32da as a promising therapeutic drug for treating ...

Research paper thumbnail of A novel ECG analog 4-(S)-(2,4,6-trimethylthiobenzyl)-epigallocatechin gallate selectively induces apoptosis of B16-F10 melanoma via activation of autophagy and ROS

Scientific reports, Feb 10, 2017

Autophagy-induced cancer cell death has become a novel strategy for the development of cancer the... more Autophagy-induced cancer cell death has become a novel strategy for the development of cancer therapeutic drugs. Numerous studies have indicated that green tea polyphenols induce both autophagy and apoptosis in a variety of cancer cells. Here, we synthesized a series of green tea polyphenol analogues, among which JP8 was shown to potently activate autophagy. JP8 treatment had a stronger effect on apoptosis in B16-F10 melanoma cells than that in normal AML-12 hepatocytes. JP8 selectively resulted in reactive oxygen species (ROS) accumulation in B16-F10 cells, and this effect was associated with corresponding increases in key components of the ER stress-mediated apoptosis pathway. Pharmacological inhibition of ROS by N-acetyl-L-cysteine (NAC) attenuated JP8-induced autophagy and apoptosis, indicating an upstream role of ROS in JP8-induced autophagy. An in vivo study showed that JP8 had significant antitumor effects in a B16-F10 xenograft mouse model. Our results indicate that JP8 is a...

Research paper thumbnail of Inhibition of miR-155 potentially protects against lipopolysaccharide-induced acute lung injury through the IRF2BP2-NFAT1 pathway

American Journal of Physiology-Cell Physiology, 2020

Sepsis-induced lung injury is a lethal complication with no effective treatment options, affectin... more Sepsis-induced lung injury is a lethal complication with no effective treatment options, affecting millions of people worldwide. Oroxylin A (OroA) is a natural flavonoid with potent anticancer effects, but its modulating effect on inflammation through microRNAs (miRs) is not apparent. In this report, we investigated the target genes of the miR pathway mediated by OroA and assessed the potential for novel treatments of septic lung injury. An miR array screening and quantitative polymerase chain reaction identified that miR-155-5p could be a candidate regulated by OroA. Bioinformatics analysis indicated that interferon regulatory factor-2-binding protein-2 (IRF2BP2) might be a target of miR-155-5p, and this hypothesis was verified through reporter assays. In addition, an immunoprecipitation assay demonstrated that OroA increased the binding activity of IRF2BP2 to the nuclear factor of activated T-cells 1 (NFAT1), causing inducible nitric oxide synthase to cause an inflammatory reactio...

Research paper thumbnail of MicroRNAs as Biomarkers and Therapeutic Targets in Inflammation- and Ischemia-Reperfusion-Related Acute Renal Injury

International Journal of Molecular Sciences, 2020

Acute kidney injury (AKI), caused mainly by ischemia-reperfusion, sepsis, or nephrotoxins (such a... more Acute kidney injury (AKI), caused mainly by ischemia-reperfusion, sepsis, or nephrotoxins (such as contrast medium), is identified by an abrupt decline in kidney function and is associated with high morbidity and mortality. Despite decades of efforts, the pathogenesis of AKI remains poorly understood, and effective therapies are lacking. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the posttranscriptional level to control cell differentiation, development, and homeostasis. Additionally, extracellular miRNAs might mediate cell–cell communication during various physiological and pathological processes. Recently, mounting evidence indicates that miRNAs play a role in the pathogenesis of AKI. Moreover, emerging research suggests that because of their remarkable stability in body fluids, microRNAs can potentially serve as novel diagnostic biomarkers of AKI. Of note, our previous finding that miR-494 is rapidly elevated in urine but not in serum provides in...

Research paper thumbnail of Epigenetic driver mutations in ARID1A shape cancer immune phenotype and immunotherapy

Journal of Clinical Investigation, 2020

Research paper thumbnail of Topological background discrimination in the PandaX-III neutrinoless double beta decay experiment

Journal of Physics G: Nuclear and Particle Physics, 2019

Research paper thumbnail of Constraining Dark Matter Models with a Light Mediator at the PandaX-II Experiment

Physical review letters, Jan 13, 2018

We search for nuclear recoil signals of dark matter models with a light mediator in PandaX-II, a ... more We search for nuclear recoil signals of dark matter models with a light mediator in PandaX-II, a direct detection experiment in the China Jinping underground laboratory. Using data collected in 2016 and 2017 runs, corresponding to a total exposure of 54 ton day, we set upper limits on the zero-momentum dark matter-nucleon cross section. These limits have a strong dependence on the mediator mass when it is comparable to or below the typical momentum transfer. We apply our results to constrain self-interacting dark matter models with a light mediator mixing with standard model particles, and set strong limits on the model parameter space for the dark matter mass ranging from 5 GeV to 10 TeV.

Research paper thumbnail of Host expression of PD-L1 determines efficacy of PD-L1 pathway blockade-mediated tumor regression

The Journal of clinical investigation, 2018

Programmed death-1 receptor (PD-L1, B7-H1) and programmed cell death protein 1 (PD-1) pathway blo... more Programmed death-1 receptor (PD-L1, B7-H1) and programmed cell death protein 1 (PD-1) pathway blockade is a promising therapy for treating cancer. However, the mechanistic contribution of host and tumor PD-L1 and PD-1 signaling to the therapeutic efficacy of PD-L1 and PD-1 blockade remains elusive. Here, we evaluated 3 tumor-bearing mouse models that differ in their sensitivity to PD-L1 blockade and demonstrated a loss of therapeutic efficacy of PD-L1 blockade in immunodeficient mice and in PD-L1- and PD-1-deficient mice. In contrast, neither knockout nor overexpression of PD-L1 in tumor cells had an effect on PD-L1 blockade efficacy. Human and murine studies showed high levels of functional PD-L1 expression in dendritic cells and macrophages in the tumor microenvironments and draining lymph nodes. Additionally, expression of PD-L1 on dendritic cells and macrophages in ovarian cancer and melanoma patients correlated with the efficacy of treatment with either anti-PD-1 alone or in co...

Research paper thumbnail of Dark Matter Results from 54-Ton-Day Exposure of PandaX-II Experiment

Physical review letters, Jan 3, 2017

We report a new search for weakly interacting massive particles (WIMPs) using the combined low ba... more We report a new search for weakly interacting massive particles (WIMPs) using the combined low background data sets acquired in 2016 and 2017 from the PandaX-II experiment in China. The latest data set contains a new exposure of 77.1 live days, with the background reduced to a level of 0.8×10^{-3} evt/kg/day, improved by a factor of 2.5 in comparison to the previous run in 2016. No excess events are found above the expected background. With a total exposure of 5.4×10^{4} kg day, the most stringent upper limit on the spin-independent WIMP-nucleon cross section is set for a WIMP with mass larger than 100 GeV/c^{2}, with the lowest 90% C.L. exclusion at 8.6×10^{-47} cm^{2} at 40 GeV/c^{2}.

Research paper thumbnail of Refractive index sensor based on tapered multicore fiber

Optical Fiber Technology, 2017

Research paper thumbnail of Effector T Cells Abrogate Stroma-Mediated Chemoresistance in Ovarian Cancer

Cell, Jan 27, 2016

Effector T cells and fibroblasts are major components in the tumor microenvironment. The means th... more Effector T cells and fibroblasts are major components in the tumor microenvironment. The means through which these cellular interactions affect chemoresistance is unclear. Here, we show that fibroblasts diminish nuclear accumulation of platinum in ovarian cancer cells, resulting in resistance to platinum-based chemotherapy. We demonstrate that glutathione and cysteine released by fibroblasts contribute to this resistance. CD8(+) T cells abolish the resistance by altering glutathione and cystine metabolism in fibroblasts. CD8(+) T-cell-derived interferon (IFN)γ controls fibroblast glutathione and cysteine through upregulation of gamma-glutamyltransferases and transcriptional repression of system xc(-) cystine and glutamate antiporter via the JAK/STAT1 pathway. The presence of stromal fibroblasts and CD8(+) T cells is negatively and positively associated with ovarian cancer patient survival, respectively. Thus, our work uncovers a mode of action for effector T cells: they abrogate str...

Research paper thumbnail of Translaparoscopic Tubal Embryo Transfer: Preliminary Experience at National Taiwan University Hospital

Asia-Oceania Journal of Obstetrics and Gynaecology, 2010

Forty-six couples with various causes of infertility were treated by tubal embryo transfer. Oocyt... more Forty-six couples with various causes of infertility were treated by tubal embryo transfer. Oocyte retrievals were carried out under ultrasound guidance transvaginally and embryos were transferred 48 hours later by laparoscopy into fallopian tubes. Totally 52 cycles were stimulated and 45 retrievals were performed with an average of 8.1 oocytes per retrieval. The average fertilization rate was 54.8%. The implantation rate was 23.8% and the pregnancy rate was 53.5% per transfer. The pregnancy rate per transfer was comparable whether 3 or 4 embryos were transferred. Nine (39.1%) of the 23 pregnancies had multiple pregnancies. Six cases (26.1%) aborted in the first trimester and the remaining 17 were ongoing or term delivery.

Research paper thumbnail of Enhanced oral bioavailability of paclitaxel by D-alpha-tocopheryl polyethylene glycol 400 succinate in mice

International journal of pharmaceutics, Jan 9, 2008

Paclitaxel is widely used to treat several types of solid tumors. The commercially available pacl... more Paclitaxel is widely used to treat several types of solid tumors. The commercially available paclitaxel formulation contains Cremophor/ethanol as solubilizers. This study evaluated the effects of D-alpha-tocopheryl polyethylene glycol 400 succinate (TPGS 400) on the oral absorption of paclitaxel in mice. Mice were given an intravenous (18mg/kg) or oral (100mg/kg) dose of paclitaxel solubilized in Cremophor/ethanol or in TPGS 400/ethanol formulations. Paclitaxel plasma concentrations and pharmacokinetic parameters were determined. The maximal plasma concentrations of paclitaxel after an oral dose were 1.77+/-0.17 and 3.39+/-0.49microg/ml for Cremophor/ethanol and TPGS 400/ethanol formulations, respectively, with a similar time at 40-47min to reach the maximal plasma concentrations. The oral bioavailability of paclitaxel in TPGS 400/ethanol (7.8%) was 3-fold higher than that in Cremophor/ethanol (2.5%). On the other hand, the plasma pharmacokinetic profiles of intravenous paclitaxel d...

Research paper thumbnail of Putative tumor metastasis-associated genes in human gastric cancer

International Journal of Oncology, 2012

Research paper thumbnail of JAK pathway induction of c-Myc critical to IL-5 stimulation of cell proliferation and inhibition of apoptosis

Journal of Cellular Biochemistry, 2009

Interleukin-5 (IL-5) induction of c-Myc expression is associated with IL-5 inhibition of apoptosi... more Interleukin-5 (IL-5) induction of c-Myc expression is associated with IL-5 inhibition of apoptosis in hematopoietic cells. In this study, TFalpha1 and TFalpha8 cells with stable overexpression of IL-5 receptor alpha (IL-5Ralpha) subunit in TF-1 cells, a human hematopoietic progenitor cell line which expressed low levels of IL-5Ralpha, were used to explored how IL-5 up-regulate c-Myc and the role of c-Myc in IL-5 signaling. First, we demonstrate that IL-5 induced c-Myc RNA and protein expressions, as well as activated Janus kinases (JAK1 and JAK2) and signal transducer and activator of transcription-5b (STAT5b). JAK inhibitor AG490 and c-Myc inhibitor 10058-F4, both, reduced IL-5-mediated cell proliferation in a dose- and time-dependent manner. Both, AG490 and 10058-F4, also reduced IL-5-mediated anti-apoptotic activity. Furthermore, AG490 inhibited IL-5-mediated c-Myc induction and promoter activity. We further examined the role of JAK1 and JAK2 in the induction of c-Myc expression using the CDJAK fusion proteins, which consisted of a CD16 extracellular domain, a CD7 transmembrane domain, and either JAK1 (CDJAK1) or JAK2 (CDJAK2) as intracellular domains. Simultaneous activation of JAK1 and JAK2 by anti-CD16 antibody crosslinking of CDJAK1 and CDJAK2 could induced c-Myc expression and promoter activity; AG490 inhibited CDJAK1 and CDJAK2-mediated effects. These results suggest that IL-5 induces cell proliferation and anti-apoptosis through the JAK/c-Myc pathway, and that JAK1 and JAK2 activation participate in IL-5-induced up-regulation of c-Myc.

Research paper thumbnail of Multiplex detection of urinary miRNA biomarkers by transmission surface plasmon resonance

The Analyst, 2018

The clinical assessment of short-stranded nucleic acid biomarkers such as miRNAs could potentiall... more The clinical assessment of short-stranded nucleic acid biomarkers such as miRNAs could potentially provide useful information for monitoring disease progression, prompting definitive treatment decisions.

Research paper thumbnail of New Synthesized Activating Transcription Factor 3 Inducer SW20.1 Suppresses Resistin-Induced Metabolic Syndrome

Biomedicines

Obesity is an emerging concern globally with increasing prevalence. Obesity is associated with ma... more Obesity is an emerging concern globally with increasing prevalence. Obesity is associated with many diseases, such as cardiovascular disease, dyslipidemia, and cancer. Thus, effective new antiobesity drugs should be urgently developed. We synthesized SW20.1, a compound that induces activating transcription factor 3 (ATF3) expression. The results of Oil Red O staining and quantitative real-time polymerase chain reaction revealed that SW20.1 was more effective in reducing lipid accumulation in 3T3-L1 preadipocytes than the previously synthesized ST32db, and that it inhibited the expression of the genes involved in adipogenesis and lipogenesis. A chromatin immunoprecipitation assay indicated that SW20.1 inhibited adipogenesis and lipogenesis by binding to the upstream promoter region of resistin at two sites (−2861/−2854 and −241/−234). In mice, the intraperitoneal administration of SW20.1 reduced body weight, white adipocyte weight in different regions, serum cholesterol levels, adipo...

Research paper thumbnail of Emergent Roles of Circular RNAs in Metabolism and Metabolic Disorders

International Journal of Molecular Sciences, 2022

Circular RNAs (circRNAs) are an emerging group of long non-coding RNAs (lncRNAs) and have attract... more Circular RNAs (circRNAs) are an emerging group of long non-coding RNAs (lncRNAs) and have attracted attention again according to the progress in high-throughput sequencing in recent years. circRNAs are genome transcripts produced from pre-messenger (m)RNA regions in a specific process called “back-splicing,” which forms covalently closed continuous loops. Due to their lack of a 5’ cap and 3’ poly-adenylated tails, circRNAs are remarkably more stable than linear RNAs. Functionally, circRNAs can endogenously sponge to microRNAs, interact with RNA-binding proteins (RBPs), or translate themselves. Moreover, circRNAs can be expressed in cell type- or tissue-specific expression patterns. Therefore, they are proposed to play essential roles in fine-tuning our body’s homeostasis by regulating transcription and translation processes. Indeed, there has been accumulating emergent evidence showing that dysregulation of circRNAs can lead to metabolic disorders. This study explored the current kn...

Research paper thumbnail of ATF3-Mediated Epigenetic Regulation Protects against Acute Kidney Injury

Journal of the American Society of Nephrology, 2010

A variety of stress stimuli, including ischemia-reperfusion (I/R) injury, induce the transcriptio... more A variety of stress stimuli, including ischemia-reperfusion (I/R) injury, induce the transcriptional repressor ATF3 in the kidney. The functional consequences of this upregulation in ATF3 after renal I/R injury are not well understood. Here, we found that ATF3-deficient mice had higher renal I/R-induced mortality, kidney dysfunction, inflammation (number of infiltrating neutrophils, myeloperoxidase activity, and induction of IL-6 and P-selectin), and apoptosis compared with wild-type mice. Furthermore, gene transfer of ATF3 to the kidney rescued the renal I/R-induced injuries in the ATF3-deficient mice. Molecular and biochemical analysis revealed that ATF3 interacted directly with histone deacetylase 1 (HDAC1) and recruited HDAC1 into the ATF/NF-B sites in the IL-6 and IL-12b gene promoters. The ATF3-associated HDAC1 deacetylated histones, which resulted in the condensation of chromatin structure, interference of NF-B binding, and inhibition of inflammatory gene transcription after I/R injury. Taken together, these data demonstrate epigenetic regulation mediated by the stress-inducible gene ATF3 after renal I/R injury and suggest potential targeted approaches for acute kidney injury.

Research paper thumbnail of Abstract 275: Activating Transcription Factor 3 Protects Against Obesity and Metabolic Dysfunction Through Promoting Lipolysis and Adipocytes Browning

Circulation Research, 2017

Recent studies implying that promoting lipolysis or enhancing brown remodeling of white adipose t... more Recent studies implying that promoting lipolysis or enhancing brown remodeling of white adipose tissue is a potential strategy to treat obesity and metabolic syndrome. Activating transcription factor 3 (ATF3) is a member of the ATF/cAMP-response element binding protein family of transcriptional factors. It is upregulated under stress condition in a variety of tissues, including the adipocytes. However, the mechanism of ATF3 in adipocytes and obesity regulation are not clear. We gave high-fat-diet (HFD) to both ATF3-/- (KO) and their wild type littermates (WT) for 16 weeks. KO showed obvious obesity as compared to WT. The obese KO mice then received AAV8-mediated gene transfer of ATF3 (AAV8-ATF3) at 16 weeks, in which decrease body weights were observed as compared to KO receiving AAV8-GFP. Histology demonstrated increased adipocyte cell diameter in KO, in which such enlargement of adipocytes can be reversed by AAV8-ATF3 therapy. We then used ATF3-overexpressing 3T3-L1 preadipocytes ...

Research paper thumbnail of Adipocyte browning and resistance to obesity in mice is induced by expression of ATF3

Communications Biology, 2019

Billions of people have obesity-related metabolic syndromes such as diabetes and hyperlipidemia. ... more Billions of people have obesity-related metabolic syndromes such as diabetes and hyperlipidemia. Promoting the browning of white adipose tissue has been suggested as a potential strategy, but a drug still needs to be identified. Here, genetic deletion of activating transcription factor 3 (ATF3−/−) in mice under a high-fat diet (HFD) resulted in obesity and insulin resistance, which was abrogated by virus-mediated ATF3 restoration. ST32da, a synthetic ATF3 inducer isolated from Salvia miltiorrhiza, promoted ATF3 expression to downregulate adipokine genes and induce adipocyte browning by suppressing the carbohydrate-responsive element-binding protein–stearoyl-CoA desaturase-1 axis. Furthermore, ST32da increased white adipose tissue browning and reduced lipogenesis in HFD-induced obese mice. The anti-obesity efficacy of oral ST32da administration was similar to that of the clinical drug orlistat. Our study identified the ATF3 inducer ST32da as a promising therapeutic drug for treating ...

Research paper thumbnail of A novel ECG analog 4-(S)-(2,4,6-trimethylthiobenzyl)-epigallocatechin gallate selectively induces apoptosis of B16-F10 melanoma via activation of autophagy and ROS

Scientific reports, Feb 10, 2017

Autophagy-induced cancer cell death has become a novel strategy for the development of cancer the... more Autophagy-induced cancer cell death has become a novel strategy for the development of cancer therapeutic drugs. Numerous studies have indicated that green tea polyphenols induce both autophagy and apoptosis in a variety of cancer cells. Here, we synthesized a series of green tea polyphenol analogues, among which JP8 was shown to potently activate autophagy. JP8 treatment had a stronger effect on apoptosis in B16-F10 melanoma cells than that in normal AML-12 hepatocytes. JP8 selectively resulted in reactive oxygen species (ROS) accumulation in B16-F10 cells, and this effect was associated with corresponding increases in key components of the ER stress-mediated apoptosis pathway. Pharmacological inhibition of ROS by N-acetyl-L-cysteine (NAC) attenuated JP8-induced autophagy and apoptosis, indicating an upstream role of ROS in JP8-induced autophagy. An in vivo study showed that JP8 had significant antitumor effects in a B16-F10 xenograft mouse model. Our results indicate that JP8 is a...

Research paper thumbnail of Inhibition of miR-155 potentially protects against lipopolysaccharide-induced acute lung injury through the IRF2BP2-NFAT1 pathway

American Journal of Physiology-Cell Physiology, 2020

Sepsis-induced lung injury is a lethal complication with no effective treatment options, affectin... more Sepsis-induced lung injury is a lethal complication with no effective treatment options, affecting millions of people worldwide. Oroxylin A (OroA) is a natural flavonoid with potent anticancer effects, but its modulating effect on inflammation through microRNAs (miRs) is not apparent. In this report, we investigated the target genes of the miR pathway mediated by OroA and assessed the potential for novel treatments of septic lung injury. An miR array screening and quantitative polymerase chain reaction identified that miR-155-5p could be a candidate regulated by OroA. Bioinformatics analysis indicated that interferon regulatory factor-2-binding protein-2 (IRF2BP2) might be a target of miR-155-5p, and this hypothesis was verified through reporter assays. In addition, an immunoprecipitation assay demonstrated that OroA increased the binding activity of IRF2BP2 to the nuclear factor of activated T-cells 1 (NFAT1), causing inducible nitric oxide synthase to cause an inflammatory reactio...

Research paper thumbnail of MicroRNAs as Biomarkers and Therapeutic Targets in Inflammation- and Ischemia-Reperfusion-Related Acute Renal Injury

International Journal of Molecular Sciences, 2020

Acute kidney injury (AKI), caused mainly by ischemia-reperfusion, sepsis, or nephrotoxins (such a... more Acute kidney injury (AKI), caused mainly by ischemia-reperfusion, sepsis, or nephrotoxins (such as contrast medium), is identified by an abrupt decline in kidney function and is associated with high morbidity and mortality. Despite decades of efforts, the pathogenesis of AKI remains poorly understood, and effective therapies are lacking. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the posttranscriptional level to control cell differentiation, development, and homeostasis. Additionally, extracellular miRNAs might mediate cell–cell communication during various physiological and pathological processes. Recently, mounting evidence indicates that miRNAs play a role in the pathogenesis of AKI. Moreover, emerging research suggests that because of their remarkable stability in body fluids, microRNAs can potentially serve as novel diagnostic biomarkers of AKI. Of note, our previous finding that miR-494 is rapidly elevated in urine but not in serum provides in...

Research paper thumbnail of Epigenetic driver mutations in ARID1A shape cancer immune phenotype and immunotherapy

Journal of Clinical Investigation, 2020

Research paper thumbnail of Topological background discrimination in the PandaX-III neutrinoless double beta decay experiment

Journal of Physics G: Nuclear and Particle Physics, 2019

Research paper thumbnail of Constraining Dark Matter Models with a Light Mediator at the PandaX-II Experiment

Physical review letters, Jan 13, 2018

We search for nuclear recoil signals of dark matter models with a light mediator in PandaX-II, a ... more We search for nuclear recoil signals of dark matter models with a light mediator in PandaX-II, a direct detection experiment in the China Jinping underground laboratory. Using data collected in 2016 and 2017 runs, corresponding to a total exposure of 54 ton day, we set upper limits on the zero-momentum dark matter-nucleon cross section. These limits have a strong dependence on the mediator mass when it is comparable to or below the typical momentum transfer. We apply our results to constrain self-interacting dark matter models with a light mediator mixing with standard model particles, and set strong limits on the model parameter space for the dark matter mass ranging from 5 GeV to 10 TeV.

Research paper thumbnail of Host expression of PD-L1 determines efficacy of PD-L1 pathway blockade-mediated tumor regression

The Journal of clinical investigation, 2018

Programmed death-1 receptor (PD-L1, B7-H1) and programmed cell death protein 1 (PD-1) pathway blo... more Programmed death-1 receptor (PD-L1, B7-H1) and programmed cell death protein 1 (PD-1) pathway blockade is a promising therapy for treating cancer. However, the mechanistic contribution of host and tumor PD-L1 and PD-1 signaling to the therapeutic efficacy of PD-L1 and PD-1 blockade remains elusive. Here, we evaluated 3 tumor-bearing mouse models that differ in their sensitivity to PD-L1 blockade and demonstrated a loss of therapeutic efficacy of PD-L1 blockade in immunodeficient mice and in PD-L1- and PD-1-deficient mice. In contrast, neither knockout nor overexpression of PD-L1 in tumor cells had an effect on PD-L1 blockade efficacy. Human and murine studies showed high levels of functional PD-L1 expression in dendritic cells and macrophages in the tumor microenvironments and draining lymph nodes. Additionally, expression of PD-L1 on dendritic cells and macrophages in ovarian cancer and melanoma patients correlated with the efficacy of treatment with either anti-PD-1 alone or in co...

Research paper thumbnail of Dark Matter Results from 54-Ton-Day Exposure of PandaX-II Experiment

Physical review letters, Jan 3, 2017

We report a new search for weakly interacting massive particles (WIMPs) using the combined low ba... more We report a new search for weakly interacting massive particles (WIMPs) using the combined low background data sets acquired in 2016 and 2017 from the PandaX-II experiment in China. The latest data set contains a new exposure of 77.1 live days, with the background reduced to a level of 0.8×10^{-3} evt/kg/day, improved by a factor of 2.5 in comparison to the previous run in 2016. No excess events are found above the expected background. With a total exposure of 5.4×10^{4} kg day, the most stringent upper limit on the spin-independent WIMP-nucleon cross section is set for a WIMP with mass larger than 100 GeV/c^{2}, with the lowest 90% C.L. exclusion at 8.6×10^{-47} cm^{2} at 40 GeV/c^{2}.

Research paper thumbnail of Refractive index sensor based on tapered multicore fiber

Optical Fiber Technology, 2017

Research paper thumbnail of Effector T Cells Abrogate Stroma-Mediated Chemoresistance in Ovarian Cancer

Cell, Jan 27, 2016

Effector T cells and fibroblasts are major components in the tumor microenvironment. The means th... more Effector T cells and fibroblasts are major components in the tumor microenvironment. The means through which these cellular interactions affect chemoresistance is unclear. Here, we show that fibroblasts diminish nuclear accumulation of platinum in ovarian cancer cells, resulting in resistance to platinum-based chemotherapy. We demonstrate that glutathione and cysteine released by fibroblasts contribute to this resistance. CD8(+) T cells abolish the resistance by altering glutathione and cystine metabolism in fibroblasts. CD8(+) T-cell-derived interferon (IFN)γ controls fibroblast glutathione and cysteine through upregulation of gamma-glutamyltransferases and transcriptional repression of system xc(-) cystine and glutamate antiporter via the JAK/STAT1 pathway. The presence of stromal fibroblasts and CD8(+) T cells is negatively and positively associated with ovarian cancer patient survival, respectively. Thus, our work uncovers a mode of action for effector T cells: they abrogate str...

Research paper thumbnail of Translaparoscopic Tubal Embryo Transfer: Preliminary Experience at National Taiwan University Hospital

Asia-Oceania Journal of Obstetrics and Gynaecology, 2010

Forty-six couples with various causes of infertility were treated by tubal embryo transfer. Oocyt... more Forty-six couples with various causes of infertility were treated by tubal embryo transfer. Oocyte retrievals were carried out under ultrasound guidance transvaginally and embryos were transferred 48 hours later by laparoscopy into fallopian tubes. Totally 52 cycles were stimulated and 45 retrievals were performed with an average of 8.1 oocytes per retrieval. The average fertilization rate was 54.8%. The implantation rate was 23.8% and the pregnancy rate was 53.5% per transfer. The pregnancy rate per transfer was comparable whether 3 or 4 embryos were transferred. Nine (39.1%) of the 23 pregnancies had multiple pregnancies. Six cases (26.1%) aborted in the first trimester and the remaining 17 were ongoing or term delivery.

Research paper thumbnail of Enhanced oral bioavailability of paclitaxel by D-alpha-tocopheryl polyethylene glycol 400 succinate in mice

International journal of pharmaceutics, Jan 9, 2008

Paclitaxel is widely used to treat several types of solid tumors. The commercially available pacl... more Paclitaxel is widely used to treat several types of solid tumors. The commercially available paclitaxel formulation contains Cremophor/ethanol as solubilizers. This study evaluated the effects of D-alpha-tocopheryl polyethylene glycol 400 succinate (TPGS 400) on the oral absorption of paclitaxel in mice. Mice were given an intravenous (18mg/kg) or oral (100mg/kg) dose of paclitaxel solubilized in Cremophor/ethanol or in TPGS 400/ethanol formulations. Paclitaxel plasma concentrations and pharmacokinetic parameters were determined. The maximal plasma concentrations of paclitaxel after an oral dose were 1.77+/-0.17 and 3.39+/-0.49microg/ml for Cremophor/ethanol and TPGS 400/ethanol formulations, respectively, with a similar time at 40-47min to reach the maximal plasma concentrations. The oral bioavailability of paclitaxel in TPGS 400/ethanol (7.8%) was 3-fold higher than that in Cremophor/ethanol (2.5%). On the other hand, the plasma pharmacokinetic profiles of intravenous paclitaxel d...

Research paper thumbnail of Putative tumor metastasis-associated genes in human gastric cancer

International Journal of Oncology, 2012

Research paper thumbnail of JAK pathway induction of c-Myc critical to IL-5 stimulation of cell proliferation and inhibition of apoptosis

Journal of Cellular Biochemistry, 2009

Interleukin-5 (IL-5) induction of c-Myc expression is associated with IL-5 inhibition of apoptosi... more Interleukin-5 (IL-5) induction of c-Myc expression is associated with IL-5 inhibition of apoptosis in hematopoietic cells. In this study, TFalpha1 and TFalpha8 cells with stable overexpression of IL-5 receptor alpha (IL-5Ralpha) subunit in TF-1 cells, a human hematopoietic progenitor cell line which expressed low levels of IL-5Ralpha, were used to explored how IL-5 up-regulate c-Myc and the role of c-Myc in IL-5 signaling. First, we demonstrate that IL-5 induced c-Myc RNA and protein expressions, as well as activated Janus kinases (JAK1 and JAK2) and signal transducer and activator of transcription-5b (STAT5b). JAK inhibitor AG490 and c-Myc inhibitor 10058-F4, both, reduced IL-5-mediated cell proliferation in a dose- and time-dependent manner. Both, AG490 and 10058-F4, also reduced IL-5-mediated anti-apoptotic activity. Furthermore, AG490 inhibited IL-5-mediated c-Myc induction and promoter activity. We further examined the role of JAK1 and JAK2 in the induction of c-Myc expression using the CDJAK fusion proteins, which consisted of a CD16 extracellular domain, a CD7 transmembrane domain, and either JAK1 (CDJAK1) or JAK2 (CDJAK2) as intracellular domains. Simultaneous activation of JAK1 and JAK2 by anti-CD16 antibody crosslinking of CDJAK1 and CDJAK2 could induced c-Myc expression and promoter activity; AG490 inhibited CDJAK1 and CDJAK2-mediated effects. These results suggest that IL-5 induces cell proliferation and anti-apoptosis through the JAK/c-Myc pathway, and that JAK1 and JAK2 activation participate in IL-5-induced up-regulation of c-Myc.