Publications by authors named "Ben Ko"

Inflammation is an important pathophysiological process in many diseases; it has beneficial and harmful effects. When exposed to various stimuli, the body triggers an inflammatory response to eliminate invaded pathogens and damaged tissues to maintain homeostasis. However, uncontrollable persistent or excessive inflammatory responses may damage tissues and induce various diseases, such as metabolic diseases (e.

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Background: Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancer cases and ranks as the second leading cause of cancer related death. Multiple receptor tyrosine kinases such as EGFR, FGFR and c-MET have been shown to drive tumorigenesis and progression of HCC. However, tyrosine kinase inhibitors (TKIs) that target these kinases, including the FDA-approved sorafenib, only offer limited clinical success.

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The health concerns of microplastics (MPs) and nanoplastics (NPs) surge, but the key indicators to evaluate the adverse risks of MPs/NPs are elusive. Recently, MPs/Ps were found to disturb glucose and lipid metabolism in rodents, suggesting that MPs/NPs may play a role in obesity progression. In this study, we firstly demonstrated that the distribution of fluorescent polystyrene nanoplastics (nPS, 60 nm) white adipose tissue (WAT) of mice.

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NFAT5 is the only known mammalian tonicity-responsive transcription factor with an essential role in cellular adaptation to hypertonic stress. It is also implicated in diverse physiological and pathological processes. NFAT5 activity is tightly regulated by extracellular tonicity, but the underlying mechanisms remain elusive.

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A novel fluorescent quinolizinium-based turn-off probe has been developed for selective detection of cysteine. The probe showed high selectivity and sensitivity towards cysteine over other amino acids including the similarly structured homocysteine and glutathione with a detection limit of 0.18 μM (S/N = 3).

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Long noncoding RNAs (lncRNAs) have gained widespread attention as a new layer of regulation in biological processes during development and disease. The lncRNA ELDR (EGFR long noncoding downstream RNA) was recently shown to be highly expressed in oral cancers as compared to adjacent nontumor tissue, and we previously reported that ELDR may be an oncogene as inhibition of ELDR reduces tumor growth in oral cancer models. Furthermore, overexpression of ELDR induces proliferation and colony formation in normal oral keratinocytes (NOKs).

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Quinoliziniums, cationic aromatic heterocycles bearing a quaternary bridgehead nitrogen, have been widely used as fluorescent dyes, DNA intercalators, ionic liquids . A library of new quinolizinium compounds was synthesized from quinolines and internal alkyne substrates in up to 65% isolated yields. Systematic studies of their photophysical properties were conducted.

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Macrophages play an important role in the host defense mechanism. In response to infection, macrophages activate a genetic program of pro-inflammatory response to kill any invading pathogen, and initiate an adaptive immune response. We have identified RUVBL2 - an ATP-binding protein belonging to the AAA+ (ATPase associated with diverse cellular activities) superfamily of ATPases - as a novel regulator in pro-inflammatory response of macrophages.

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Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

Autophagy

January 2021

Article Synopsis
  • In 2008, guidelines were established for researching autophagy, which has since gained significant interest and new technologies, necessitating regular updates to monitoring methods across various organisms.
  • The new guidelines emphasize selecting appropriate techniques to evaluate autophagy while noting that no single method suits all situations; thus, a combination of methods is encouraged.
  • The document highlights that key proteins involved in autophagy also impact other cellular processes, suggesting genetic studies should focus on multiple autophagy-related genes to fully understand these pathways.
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We previously described the protective role of the nuclear factor of activated T cells 5 (NFAT5) during hypoxia. Alternatively, inducible nitric oxide synthase (iNOS) is also induced by hypoxia. Some evidence indicates that NFAT5 is essential for the expression of iNOS in Toll-like receptor-stimulated macrophages and that iNOS inhibition increases NFAT5 expression in renal ischemia-reperfusion.

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CCCTC-binding factor (CTCF) is a DNA-binding protein that interacts with a large number of highly divergent target sequences throughout the genome. It is implicated in a variety of functions, including chromatin organization and transcriptional control. The functional role of CTCF in tumour pathogenesis remains elusive.

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Emerging evidence suggests the therapeutic role of autophagic modulators in cancer therapy. This study aims to identify novel traditional Chinese medicinal herbs as potential anti-tumor agents through autophagic induction, which finally lead to autophagy mediated-cell death in apoptosis-resistant cancer cells. Using bioactivity-guided purification, we identified tetrandrine (Tet) from herbal plant, , as an inducer of autophagy.

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A growing body of evidence suggests that secretin (SCT) is an important element in the osmoregulatory pathway. It is interesting to note that both SCT and its receptor (SCTR) gene are activated upon hyperosmolality in the kidney. However, the precise molecular mechanisms underlying the induction of the SCTR gene expression in response to changes in osmolality have yet to be clarified.

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Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase that is implicated in plethora of biological processes, including metabolism, aging, stress response, and tumorigenesis. Telomerase (TERT) is essential for telomere maintenance. Activation of TERT is considered a crucial step in tumorigenesis, and therefore it is a potential therapeutic target against cancer.

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Article Synopsis
  • Chronic hepatitis B virus (HBV) infection increases the risk of liver cirrhosis and cancer, but how HBV replicates at the molecular level is still not fully understood.
  • Researchers discovered that SIRT1, a histone deacetylase, is upregulated in HBV-infected cells and plays a crucial role in enhancing HBV replication by activating the HBV core promoter through the AP-1 transcription factor.
  • Inhibiting SIRT1 reduced HBV replication and suggests that targeting SIRT1 could be a potential treatment strategy for HBV infections.
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The Nuclear Factor of Activated T Cells-5 (NFAT5), also known as OREBP or TonEBP, is a member of the nuclear factors of the activated T cells family of transcription factors. It is also the only known tonicity-regulated transcription factor in mammals. NFAT5 was initially known for its role in the hypertonic kidney inner medulla for orchestrating a genetic program to restore the cellular homeostasis.

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Unlabelled: Sirtuin 1 (SIRT1) has been implicated in telomere maintenance and the growth of hepatocellular carcinoma (HCC). Nevertheless, the role of other sirtuins in the pathogenesis of HCC remains elusive. We found that sirtuin 2 (SIRT2), another member of the sirtuin family, also contributes to cell motility and invasiveness of HCC.

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Nuclear factor of activated T cells 5 (NFAT5) has been implicated in regulating several genes that are thought to be neuroprotective in ischemic injury. Because of the embryonic lethality of NFAT5 knockout (NFAT5(-/-)) mice, the heterozygous (NFAT5(+/-)) mice were used to study the in vivo role of NFAT5 in hypoxia/ischemia (H/I) condition. The NFAT5(+/-) mice exhibited more severe neurological deficits, larger infarct area and edema formation associated with increased aquaporin 4 expressions in the brain.

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Nuclear factor of activated T cells 5 protein (NFAT5) is thought to be important for cellular adaptation to osmotic stress by regulating the transcription of genes responsible for the synthesis or transport of organic osmolytes. It is also thought to play a role in immune function, myogenesis and cancer invasion. To better understand the function of NFAT5, we developed NFAT5 gene knockout mice.

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Hepatocellular carcinoma (HCC) is a highly malignant tumor with a poor prognosis. Treatment of HCC is complicated by the fact that the disease is often diagnosed at an advanced stage when it is no longer amenable to curative surgery, and current systemic chemotherapeutics are mostly inefficacious. Sirtuin 1 (SIRT1) is a class III histone deacetylase that is implicated in gene regulations and stress resistance.

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Hepatitis B virus infection is a worldwide epidemic and is closely associated with the development of hepatocellular carcinoma. Nevertheless, the molecular mechanisms of HBV infection and carcinogenesis remain elusive. Using a hepatocyte model of HBV infection and comparing the gene expression profiling analysis we found that heparan sulfate D-glucosaminyl 3-O-sulfotransferase 3 B1 (HS3ST3B1,3-OST3-B) is down-regulated in the hepatocytes of chronic HBV infection model.

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The pseudolaric acids are diterpenoids isolated from the root bark of Pseudolarix amabilis, or the golden larch. Pseudolaric acids A and B are the major antifungal and anti-angiogenic congeners of this family of compounds. This review presents the results of the isolation, biological and synthetic studies of these natural products.

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Emerging evidence suggests that autophagic modulators have therapeutic potential. This study aims to identify novel autophagic inducers from traditional Chinese medicinal herbs as potential antitumor agents. Using an image-based screen and bioactivity-guided purification, we identified alisol B 23-acetate, alisol A 24-acetate, and alisol B from the rhizome of Alisma orientale as novel inducers of autophagy, with alisol B being the most potent natural product.

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A cytotoxic artemisinin derivative conjugated with a fluorescent dansyl moiety was synthesized and its subcellular localization in Hep3B cells was examined. Comparison of the localization signals of the fluorescent artemisinin derivative with organelle specific dyes revealed that endoplasmic reticulum (ER) is the main site of its accumulation.

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