Papers by Thiranut Jaroonwitchawan
BioMed Research International, Jan 21, 2019
Curcumin is a natural polyphenolic compound, isolated from Curcuma longa, and is an important ing... more Curcumin is a natural polyphenolic compound, isolated from Curcuma longa, and is an important ingredient of Asian foods. Curcumin has revealed its strong activities of anti-inflammatory, antioxidant, and anticancer. The efficient amount of curcumin could induce differentiation of stem cells and promoted the differentiation of glioma-initiating cells; however, the mechanisms underlying neural induction of curcumin have not yet been revealed. In this study, neural-inducing ability of curcumin was explored by using human pluripotent embryonal carcinoma cells, NTERA2 cells. The cells were induced toward neural lineage with curcumin and were compared with a standard neutralizing agent (retinoic acid). It was found that, after 14 days of the induction by curcumin, NTERA2 cells showed neuronal morphology and expressed neural-specific genes, including NeuroD, TUJ , and PAX. Importantly, curcumin activated neurogenesis of NTERA2 cells via the activation of autophagy, since autophagy-related genes, such as LC , LAMP , and ATG , were upregulated along with the expression of neural genes. The inhibition of autophagy by chloroquine suppressed both autophagy and neural differentiation, highlighting the positive role of autophagy during neural differentiation. This autophagy-mediated neural differentiation of curcumin was found to be an ROS-dependent manner; curcumin induced ROS generation and suppressed antioxidant gene expression. Altogether, this study proposed the neural-inducing activity of curcumin via the regulation of autophagy within NTERA2 cells and underscored the health beneficial effects of curcumin for neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease.
In Vitro Cellular & Developmental Biology – Animal, Aug 22, 2018
Neuroblastoma is the most common cancer of the sympathetic nervous system in children. Here, the ... more Neuroblastoma is the most common cancer of the sympathetic nervous system in children. Here, the influences of curcumin on survival, apoptosis, migration, and its combined effects with doxorubicin were investigated in SH-SY5Y cells by cell survival assay, flow cytometry, migration assays, and RT-PCR. Curcumin inhibited SH-SY5Y cell growth and induced apoptosis in doseand time-dependent manners. This apoptotic induction relied on the upregulation of p53 and p21. Moreover, the treatment of curcumin for 24 h significantly suppressed cell migration, together with the downregulation of matrix metalloproteinase-2 (MMP-2) and upregulation of tissue inhibitor of metalloproteinases-1 (TIMP-1). The combination of curcumin augmented the anticancer activity of doxorubicin and significantly induced apoptosis. Pretreatment with curcumin increased the fraction of doxorubicin-induced apoptotic cells from 21.76 ± 0.50 to 57.74 ± 2.68%. Co-treatment with doxorubicin plus curcumin further inhibited 3D tumor migration. Altogether, the results suggest that curcumin suppresses growth and migration of SH-SY5Y cells and enhances the anticancer activity of doxorubicin. The addition of curcumin to therapeutic regimens may be promising for the treatment of neuroblastomas if a number of problems related to its in vivo bioavailability can be resolved.
Frontiers in Immunology, Jun 9, 2020
FcgRIIB dysfunction is commonly found in patients with lupus, especially in Asia. LPS-tolerance i... more FcgRIIB dysfunction is commonly found in patients with lupus, especially in Asia. LPS-tolerance is prominent in FcgRIIB-/-lupus mice. LPS-tolerant macrophages demonstrate cell energy depletion, which might affect lipid metabolism. Therefore, to explore lipid metabolism, LPS-tolerance was induced twice by LPS administration in macrophages and in mice. LPS-tolerant FcgRIIB-/-macrophages demonstrated lesser mitochondrial DNA (mtDNA), more severe ATP depletion, lower cytokine production, and higher lipid accumulation (oil red O staining) compared to LPS-tolerant WT cells. Mass-spectrometry-based lipidomic analysis demonstrated a higher abundance of phosphatidylethanolamine (PE) phospholipid in LPS-tolerant FcgRIIB-/-macrophages than WT cells. This was at least in part due to the lower expression of phosphatidylethanolamine N-methyltransferase (pemt), an enzyme that converts PE to phosphatidylcholine (PC). Aminoimidazole-4-carboxamide ribonucleotide (AICAR), a pemt inhibitor, worsens LPS-tolerance in WT macrophages and supports the impact of pemt upon LPS-tolerant FcgRIIB-/-macrophages. Additionally, phosphorylated AMP-activated protein kinase (AMPK-p), a molecule for ATP-restoration associated with pemt, and phosphorylated acetyl CoA carboxylase, a downstream signaling of AMPK-p, were higher in LPS-tolerant FcgRIIB-/-macrophages than WT. Furthermore, Compound C, an AMPK inhibitor, attenuated LPS-tolerance in both FcgRIIB-/-macrophages and mice. Taken together, the intense decrease in cytokine production after the second LPS stimulation (LPS-tolerance) in FcgRIIB-/-macrophages was possibly due to the impact of an immense cytokine synthesis after the first dose of LPS. This includes using up PEMT, an enzyme of phospholipid synthesis during cytokine production, and AMPK-p induction in response to profound ATP-depletion. Therefore, the manipulation of the AMPK/PEMT axis provides a novel therapeutic candidate for the treatment of severe LPS-tolerance in lupus.
Neuroscience Letters, 2017
Paraquat is a neurotoxic agent, and oxidative stress plays an important role in neuronal cell dea... more Paraquat is a neurotoxic agent, and oxidative stress plays an important role in neuronal cell death after paraquat exposure. In this study, we assessed the neuroprotective effect of curcumin against paraquat and explored the underlying mechanisms of curcumin in vitro. Curcumin treatment prevented paraquat-induced reactive oxygen species (ROS) and apoptotic cell death. Curcumin also exerted a neuroprotective effect by increasing the expression of anti-apoptotic and antioxidant genes. The pretreatment of curcumin significantly decreased gene expression and protein production of amyloid precursor protein. The activation of autophagy process was found defective in paraquat-induced cells, indicated by the accumulation and reduction of LC3I/II. Noteworthy, curcumin restored LC3I/II expression after the pretreatment. Collectively, curcumin demonstrated as a prominent suppressor of ROS, and could reverse autophagy induction in SH-SY5Y cells. The consequences of this were the reduction of APP production and prevention of SH-SY5Y cells from apoptosis. Altogether, curcumin potentially serves as a therapeutic agent of neurodegenerative diseases, associated with ROS overproduction and autophagy dysfunction.
Anti-Cancer Drugs, Jun 1, 2017
Neuroblastoma is one of the most common cancers in infancy, arising from the neuroblasts during e... more Neuroblastoma is one of the most common cancers in infancy, arising from the neuroblasts during embryonic development. This cancer is difficult to treat and resistance to chemotherapy is often found; therefore, clinical trials of novel therapeutic approaches, such as targeted-cancer signaling, could be an alternative for a better treatment. WNT signaling plays significant roles in the survival, proliferation, and differentiation of human neuroblastoma. In this report, WNT signaling of a malignant human neuroblastoma cell line, SH-SY5Y cells, was inhibited by XAV939, a specific inhibitor of the Tankyrase enzyme. XAV939 treatment led to the reduction of β-catenin within the cells, confirming its inhibitory effect of WNT. The inhibition of WNT signaling by XAV939 did not affect cell morphology, survival, and proliferation; however, the differentiation and sensitivity to anticancer drugs of human neuroblastoma cells were altered. The treatment of XAV939 resulted in the downregulation of mature neuronal markers, including β-tubulin III, PHOX2A, and PHOX2B, whereas neural progenitor markers (PAX6, TFAP2α, and SLUG) were upregulated. In addition, the combination of XAV939 significantly enhanced the sensitivity of SH-SY5Y and IMR-32 cells to doxorubicin in both 2D and 3D culture systems. Microarray gene expression profiling suggested numbers of candidate target genes of WNT inhibition by XAV939, in particular, p21, p53, ubiquitin C, ZBED8, MDM2, CASP3, and FZD1, and this explained the enhanced sensitivity of SH-SY5Y cells to doxorubicin. Altogether, these results proposed that the altered differentiation of human malignant neuroblastoma cells by inhibiting WNT signaling sensitized the cells to anticancer drugs. This approach could thus serve as an effective treatment option for aggressive brain malignancy. Anti-Cancer Drugs 28:469-479
Toxicology in Vitro, Feb 1, 2018
Brain cancer, in particular neuroblastoma and glioblastoma, is a global challenge to human health... more Brain cancer, in particular neuroblastoma and glioblastoma, is a global challenge to human health. Cordycepin, extracted from Cordyceps ssp., has been revealed as a strong anticancer agent through several ways; however, the mechanism, by which cordycepin counteracts brain cancers, is still poorly understood. In this study, the underlying mechanisms of cordycepin against human brain cancer cells were explored. SH-SY5Y and U251 cells were being a model to represent human neuroblastoma and glioblastoma, respectively. Here, it was found that cordycepin inhibited cell growth, and induced apoptosis in a dose-dependent manner in both SH-SY5Y and U-251 cell lines. The expression of pro-apoptotic genes, including P53, BAX, Caspase-3, and Caspase-9, were upregulated, whereas the expression of anti-apoptotic gene, BCL-2, was suppressed. Besides, cordycepin induced the generation of reactive oxygen species (ROS) along with the suppression of antioxidant genes, including GPX, SOD, and Catalase. Importantly, cordycepin was shown to involve in the activation of autophagy, which was evidenced by the increment of LC3I/II. The combination of cordycepin with chloroquine, an autophagy inhibitor, further inhibited the growth, and enhanced the death of brain cancer cells. Altogether, this finding suggested that cordycepin induced apoptosis of human brain cancer cells through mitochondrial-mediated intrinsic pathway and the modulation of autophagy. Therefore, cordycepin could be a promising candidate for the development of anticancer drugs targeting human brain cancers.
Biochemical and Biophysical Research Communications, Dec 1, 2016
Neural crest (NC) is a transient population, arising during embryonic development and capable of ... more Neural crest (NC) is a transient population, arising during embryonic development and capable of differentiating into various somatic cells. The defects of neural crest development leads to neurocristopathy. Several signaling pathways were revealed their significance in NC cell specification. Fibroblast growth factor (FGF) is recognized as an important signaling during NC development, for instance Xenopus and avian; however, its contributions in human species are remained elusive. Here we used human pluripotent stem cells (hPSCs) to investigate the consequences of FGF inhibition during NC cell differentiation. The specific-FGF receptor inhibitor, SU5402, was used in this investigation. The inhibition of FGF did not found to affect the proliferation or death of hPSC-derived NC cells, but promoted hPSCs to commit NC cell fate. NC-specific genes, including PAX3, SLUG, and TWIST1, were highly upregulated, while hPSC genes, such as OCT4, and E-CAD, rapidly reduced upon FGF signaling blockage. Noteworthy, TFAP-2a, a marker of migratory NC cells, abundantly presented in SU5402-induced cells. This accelerated NC cell differentiation could be due to the activation of Notch signaling upon the blockage of ERK1/2 phosphorylation, since NICD was increased by SU5402. Altogether, this study proposed the contributions of FGF signaling in controlling human NC cell differentiation from hPSCs, the crosstalk between FGF and Notch, and might imply to the influences of FGF signaling in neurocristophatic diseases.
Frontiers in Immunology, Jan 27, 2023
FXR is a key molecule that modulates anti-inflammatory activity in the intestinalliver axis. Alth... more FXR is a key molecule that modulates anti-inflammatory activity in the intestinalliver axis. Although FXR has pleiotropic functions including regulation of liver inflammation and activation of macrophages, it remains unclear whether it is involved in macrophage polarization. In this paper we demonstrated that stimulation of macrophages derived from the bone marrow using an FXR agonist activated polarization toward M2 but not M1 macrophages. The treatment of mice with chitin skewed macrophage polarization towards M2 macrophages, while cotreatment with an FXR agonist further promoted the polarization toward M2 macrophages in vivo. This skewed polarization towards M2 macrophages by an FXR agonist was accompanied by increased expression of signaling molecules related to the retinoic acid receptor. Inhibition of the retinoic acid receptor suppressed FXR agonist-mediated M2 macrophage polarization, indicating that this polarization was, at least, partly dependent on the retinoic acid receptor pathway. These data demonstrate that FXR has a role in polarization toward M2 macrophages and suggest a possible therapeutic potential of FXR agonists in M2 macrophage-related conditions.
The sensing of various extrinsic stimuli triggers the receptor-interacting protein kinase-3 (RIPK... more The sensing of various extrinsic stimuli triggers the receptor-interacting protein kinase-3 (RIPK3)-mediated signaling pathway, which leads to mixed-lineage kinase-like (MLKL) phosphorylation followed by necroptosis. Although necroptosis is a form of cell death and is involved in inflammatory conditions, the roles of necroptosis in acute pancreatitis (AP) remain unclear. In the current study, we administered caerulein to Ripk3- or Mlkl-deficient mice (Ripk3-/- or Mlkl-/- mice, respectively) and assessed the roles of necroptosis in AP. We found that Ripk3-/- mice had significantly more severe pancreatic edema and inflammation associated with macrophage and neutrophil infiltration than control mice. Consistently, Mlkl-/- mice were more susceptible to caerulein-induced AP, which occurred in a time- and dose-dependent manner, than control mice. Mlkl-/- mice exhibit weight loss, edematous pancreatitis, necrotizing pancreatitis, and acinar cell dedifferentiation in response to tissue dama...
Cell Death & Disease, 2021
The sensing of various extrinsic stimuli triggers the receptor-interacting protein kinase-3 (RIPK... more The sensing of various extrinsic stimuli triggers the receptor-interacting protein kinase-3 (RIPK3)-mediated signaling pathway, which leads to mixed-lineage kinase-like (MLKL) phosphorylation followed by necroptosis. Although necroptosis is a form of cell death and is involved in inflammatory conditions, the roles of necroptosis in acute pancreatitis (AP) remain unclear. In the current study, we administered caerulein to Ripk3- or Mlkl-deficient mice (Ripk3−/− or Mlkl−/− mice, respectively) and assessed the roles of necroptosis in AP. We found that Ripk3−/− mice had significantly more severe pancreatic edema and inflammation associated with macrophage and neutrophil infiltration than control mice. Consistently, Mlkl−/− mice were more susceptible to caerulein-induced AP, which occurred in a time- and dose-dependent manner, than control mice. Mlkl−/− mice exhibit weight loss, edematous pancreatitis, necrotizing pancreatitis, and acinar cell dedifferentiation in response to tissue dama...
Scientific Reports, 2020
The influence of gut-leakage or gut-microbiota upon lupus progression was explored in 2 lupus mou... more The influence of gut-leakage or gut-microbiota upon lupus progression was explored in 2 lupus mouse models. Pristane, administered in 4-wk-old wild-type (WT) female mice, induced lupus characteristics at 24-wk-old similar to the lupus-onset in FcGRIIb−/− mice. Gut-microbiota alteration was induced by co-housing together with the gavage of feces from 40-wk-old FcGRIIb−/− mice (symptomatic lupus). On the other hand, gut-leakage was induced by dextran sulfate solution (DSS). DSS and gut-microbiota alteration induced high serum anti-dsDNA immunoglobulin (Ig) as early as 30 days post-DSS only in FcGRIIb−/− mice. DSS, but not gut-microbiota alteration, enhanced lupus characteristics (serum creatinine and proteinuria) in both lupus models (but not in WT) at 60 days post-DSS. Indeed, DSS induced the translocation of molecular components of gut-pathogens as determined by bacterial burdens in mesenteric lymph node (MLN), endotoxemia (gut-bacterial molecule) and serum (1→3)-β-D-glucan (BG) (...
International Journal of Molecular Sciences, 2019
Dysfunction of FcGRIIb, the only inhibitory receptor of the FcGR family, is commonly found in the... more Dysfunction of FcGRIIb, the only inhibitory receptor of the FcGR family, is commonly found in the Asian population and is possibly responsible for the extreme endotoxin exhaustion in lupus. Here, the mechanisms of prominent endotoxin (LPS) tolerance in FcGRIIb−/− mice were explored on bone marrow-derived macrophages using phosphoproteomic analysis. As such, LPS tolerance decreased several phosphoproteins in the FcGRIIb−/− macrophage, including protein kinase C-β type II (PRKCB), which was associated with phagocytosis function. Overexpression of PRKCB attenuated LPS tolerance in RAW264.7 cells, supporting the role of this gene in LPS tolerance. In parallel, LPS tolerance in macrophages and in mice was attenuated by phorbol 12-myristate 13-acetate (PMA) administration. This treatment induced several protein kinase C families, including PRKCB. However, PMA attenuated the severity of mice with cecal ligation and puncture on LPS tolerance preconditioning in FcGRIIb−/− but not in wild-typ...
In Vitro Cellular & Developmental Biology - Animal, 2018
Neuroblastoma is the most common cancer of the sympathetic nervous system in children. Here, the ... more Neuroblastoma is the most common cancer of the sympathetic nervous system in children. Here, the influences of curcumin on survival, apoptosis, migration, and its combined effects with doxorubicin were investigated in SH-SY5Y cells by cell survival assay, flow cytometry, migration assays, and RT-PCR. Curcumin inhibited SH-SY5Y cell growth and induced apoptosis in doseand time-dependent manners. This apoptotic induction relied on the upregulation of p53 and p21. Moreover, the treatment of curcumin for 24 h significantly suppressed cell migration, together with the downregulation of matrix metalloproteinase-2 (MMP-2) and upregulation of tissue inhibitor of metalloproteinases-1 (TIMP-1). The combination of curcumin augmented the anticancer activity of doxorubicin and significantly induced apoptosis. Pretreatment with curcumin increased the fraction of doxorubicin-induced apoptotic cells from 21.76 ± 0.50 to 57.74 ± 2.68%. Co-treatment with doxorubicin plus curcumin further inhibited 3D tumor migration. Altogether, the results suggest that curcumin suppresses growth and migration of SH-SY5Y cells and enhances the anticancer activity of doxorubicin. The addition of curcumin to therapeutic regimens may be promising for the treatment of neuroblastomas if a number of problems related to its in vivo bioavailability can be resolved.
Shock, 2019
The influence of gut fungi in chronic colitis was investigated by repeated oral administration of... more The influence of gut fungi in chronic colitis was investigated by repeated oral administration of Candida albicans in a 3% dextran sulfate solution (DSS) induced-colitis mouse model. Candida administration in the DSS (DSS+Candida) model enhanced the mortality rate and induced bacteremia (without candidemia) resulting from a gut perm-selectivity defect despite similar diarrheal severity in mice treated with DSS alone. The dominant fecal bacteria in DSS+Candida and DSS alone mice were Pseudomonas spp. and Enterobacter spp., respectively, implying that Candida induced gut dysbiosis. Interestingly, chloramphenicol-resistant bacterial colonies, predominantly Pseudomonas spp., appeared in the feces and blood of DSS+Candida mice (not the DSS alone group) during fungal culture. These antibiotic-resistant bacteria were also isolated, ex vivo, by incubating mouse feces with DSS and heat-killed Candida or (1→3)-β-D-glucan, suggesting bacterial fermentation on fungi. Administration of Pseudomon...
BioMed Research International, 2019
Curcumin is a natural polyphenolic compound, isolated from Curcuma longa, and is an important ing... more Curcumin is a natural polyphenolic compound, isolated from Curcuma longa, and is an important ingredient of Asian foods. Curcumin has revealed its strong activities of anti-inflammatory, antioxidant, and anticancer. The efficient amount of curcumin could induce differentiation of stem cells and promoted the differentiation of glioma-initiating cells; however, the mechanisms underlying neural induction of curcumin have not yet been revealed. In this study, neural-inducing ability of curcumin was explored by using human pluripotent embryonal carcinoma cells, NTERA2 cells. The cells were induced toward neural lineage with curcumin and were compared with a standard neutralizing agent (retinoic acid). It was found that, after 14 days of the induction by curcumin, NTERA2 cells showed neuronal morphology and expressed neural-specific genes, includingNeuroD,TUJ1, andPAX6. Importantly, curcumin activated neurogenesis of NTERA2 cells via the activation of autophagy, since autophagy-related ge...
Toxicology in Vitro, 2018
Brain cancer, in particular neuroblastoma and glioblastoma, is a global challenge to human health... more Brain cancer, in particular neuroblastoma and glioblastoma, is a global challenge to human health. Cordycepin, extracted from Cordyceps ssp., has been revealed as a strong anticancer agent through several ways; however, the mechanism, by which cordycepin counteracts brain cancers, is still poorly understood. In this study, the underlying mechanisms of cordycepin against human brain cancer cells were explored. SH-SY5Y and U251 cells were being a model to represent human neuroblastoma and glioblastoma, respectively. Here, it was found that cordycepin inhibited cell growth, and induced apoptosis in a dose-dependent manner in both SH-SY5Y and U-251 cell lines. The expression of pro-apoptotic genes, including P53, BAX, Caspase-3, and Caspase-9, were upregulated, whereas the expression of anti-apoptotic gene, BCL-2, was suppressed. Besides, cordycepin induced the generation of reactive oxygen species (ROS) along with the suppression of antioxidant genes, including GPX, SOD, and Catalase. Importantly, cordycepin was shown to involve in the activation of autophagy, which was evidenced by the increment of LC3I/II. The combination of cordycepin with chloroquine, an autophagy inhibitor, further inhibited the growth, and enhanced the death of brain cancer cells. Altogether, this finding suggested that cordycepin induced apoptosis of human brain cancer cells through mitochondrial-mediated intrinsic pathway and the modulation of autophagy. Therefore, cordycepin could be a promising candidate for the development of anticancer drugs targeting human brain cancers.
Anti-Cancer Drugs, 2017
Neuroblastoma is one of the most common cancers in infancy, arising from the neuroblasts during e... more Neuroblastoma is one of the most common cancers in infancy, arising from the neuroblasts during embryonic development. This cancer is difficult to treat and resistance to chemotherapy is often found; therefore, clinical trials of novel therapeutic approaches, such as targeted-cancer signaling, could be an alternative for a better treatment. WNT signaling plays significant roles in the survival, proliferation, and differentiation of human neuroblastoma. In this report, WNT signaling of a malignant human neuroblastoma cell line, SH-SY5Y cells, was inhibited by XAV939, a specific inhibitor of the Tankyrase enzyme. XAV939 treatment led to the reduction of β-catenin within the cells, confirming its inhibitory effect of WNT. The inhibition of WNT signaling by XAV939 did not affect cell morphology, survival, and proliferation; however, the differentiation and sensitivity to anticancer drugs of human neuroblastoma cells were altered. The treatment of XAV939 resulted in the downregulation of mature neuronal markers, including β-tubulin III, PHOX2A, and PHOX2B, whereas neural progenitor markers (PAX6, TFAP2α, and SLUG) were upregulated. In addition, the combination of XAV939 significantly enhanced the sensitivity of SH-SY5Y and IMR-32 cells to doxorubicin in both 2D and 3D culture systems. Microarray gene expression profiling suggested numbers of candidate target genes of WNT inhibition by XAV939, in particular, p21, p53, ubiquitin C, ZBED8, MDM2, CASP3, and FZD1, and this explained the enhanced sensitivity of SH-SY5Y cells to doxorubicin. Altogether, these results proposed that the altered differentiation of human malignant neuroblastoma cells by inhibiting WNT signaling sensitized the cells to anticancer drugs. This approach could thus serve as an effective treatment option for aggressive brain malignancy. Anti-Cancer Drugs 28:469-479
Biochemical and Biophysical Research Communications, 2016
Neural crest (NC) is a transient population, arising during embryonic development and capable of ... more Neural crest (NC) is a transient population, arising during embryonic development and capable of differentiating into various somatic cells. The defects of neural crest development leads to neurocristopathy. Several signaling pathways were revealed their significance in NC cell specification. Fibroblast growth factor (FGF) is recognized as an important signaling during NC development, for instance Xenopus and avian; however, its contributions in human species are remained elusive. Here we used human pluripotent stem cells (hPSCs) to investigate the consequences of FGF inhibition during NC cell differentiation. The specific-FGF receptor inhibitor, SU5402, was used in this investigation. The inhibition of FGF did not found to affect the proliferation or death of hPSC-derived NC cells, but promoted hPSCs to commit NC cell fate. NC-specific genes, including PAX3, SLUG, and TWIST1, were highly upregulated, while hPSC genes, such as OCT4, and E-CAD, rapidly reduced upon FGF signaling blockage. Noteworthy, TFAP-2a, a marker of migratory NC cells, abundantly presented in SU5402-induced cells. This accelerated NC cell differentiation could be due to the activation of Notch signaling upon the blockage of ERK1/2 phosphorylation, since NICD was increased by SU5402. Altogether, this study proposed the contributions of FGF signaling in controlling human NC cell differentiation from hPSCs, the crosstalk between FGF and Notch, and might imply to the influences of FGF signaling in neurocristophatic diseases.
Neuroscience Letters, 2017
Paraquat is a neurotoxic agent, and oxidative stress plays an important role in neuronal cell dea... more Paraquat is a neurotoxic agent, and oxidative stress plays an important role in neuronal cell death after paraquat exposure. In this study, we assessed the neuroprotective effect of curcumin against paraquat and explored the underlying mechanisms of curcumin in vitro. Curcumin treatment prevented paraquat-induced reactive oxygen species (ROS) and apoptotic cell death. Curcumin also exerted a neuroprotective effect by increasing the expression of anti-apoptotic and antioxidant genes. The pretreatment of curcumin significantly decreased gene expression and protein production of amyloid precursor protein. The activation of autophagy process was found defective in paraquat-induced cells, indicated by the accumulation and reduction of LC3I/II. Noteworthy, curcumin restored LC3I/II expression after the pretreatment. Collectively, curcumin demonstrated as a prominent suppressor of ROS, and could reverse autophagy induction in SH-SY5Y cells. The consequences of this were the reduction of APP production and prevention of SH-SY5Y cells from apoptosis. Altogether, curcumin potentially serves as a therapeutic agent of neurodegenerative diseases, associated with ROS overproduction and autophagy dysfunction.
Stem Cells International, 2016
Although the mechanism of neurogenesis has been well documented in other organisms, there might b... more Although the mechanism of neurogenesis has been well documented in other organisms, there might be fundamental differences between human and those species referring to species-specific context. Based on principles learned from other systems, it is found that the signaling pathways required for neural induction and specification of human embryonic stem cells (hESCs) recapitulated those in the early embryo developmentin vivoat certain degree. This underscores the usefulness of hESCs in understanding early human neural development and reinforces the need to integrate the principles of developmental biology and hESC biology for an efficient neural differentiation.
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Papers by Thiranut Jaroonwitchawan