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Article ; Online: Intermittent compressive force regulates human periodontal ligament cell behavior via yes-associated protein

Klincumhom, Nuttha / Lorthongpanich, Chanchao / Thumanu, Kanjana / Septham, Praphasri / Phomyu, Wutthikiat / Issaragrisil, Surapol / Pavasant, Prasit

Heliyon. 2022 Oct., v. 8, no. 10 p.e10845-

2022

Abstract: Intermittent compressive force influences human periodontal ligament (PDL) cell behavior that facilitates periodontal tissue regeneration. In response to mechanical stimuli, Yes-associated protein (YAP) has been recognized as a mechanosensitive ... ...

Abstract	Intermittent compressive force influences human periodontal ligament (PDL) cell behavior that facilitates periodontal tissue regeneration. In response to mechanical stimuli, Yes-associated protein (YAP) has been recognized as a mechanosensitive transcriptional activator that regulates cell proliferation and cell fate decisions. This study aimed to investigate whether compressive forces influence cell proliferation and cell fate decisions of human PDL cells via YAP signaling. YAP expression was silenced by shRNA. The effect of YAP on cell proliferation, adipogenesis and osteogenesis of PDL cells under ICF loading were determined. Adipogenic differentiation bias upon ICF loading was confirmed by fourier-transform infrared spectroscopy (FTIR). The results revealed that ICF-induced YAP promotes osteogenesis, but it inhibits adipogenesis in PDL cells. Depletion of YAP results in PDL cells that are irresponsive to ICF and, therefore, the failure of the PDL cells to undergo osteogenic differentiation. This was shown by a significant reduction in calcium deposited in the CF-derived osteoblasts of the YAP-knockdown (YAP-KD) PDL cells. As to control treatment, reduction of YAP promoted adipogenesis, whereas ICF-induced YAP inhibited this mechanism. However, the adipocyte differentiation in YAP-KD cells was not affected upon ICF treatment as the YAP-KD cells still exhibited a better adipogenic differentiation that was unrelated to the ICF. This study demonstrated that, in response to ICF treatment, YAP could be a crucial mechanosensitive transcriptional activator for the regulation of PDL cell behavior through a mechanobiological process. Our results may provide the possibility of facilitating PDL tissue regeneration by manipulation of the Hippo-YAP signaling pathway.
Keywords	Fourier transform infrared spectroscopy ; adipocytes ; adipogenesis ; bone formation ; calcium ; cell proliferation ; humans ; ligaments ; osteoblasts ; tissue repair ; transactivators ; Cell fate decision ; FTIR ; Hippo signaling pathway ; Human periodontal ligament cells ; Intermittent compressive force ; Yes-associated protein
Language	English
Dates of publication	2022-10
Publishing place	Elsevier Ltd
Document type	Article ; Online
Note	Pre-press version ; Use and reproduction
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2022.e10845
Database	NAL-Catalogue (AGRICOLA)

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Article: Intermittent compressive force regulates human periodontal ligament cell behavior via yes-associated protein.

Klincumhom, Nuttha / Lorthongpanich, Chanchao / Thumanu, Kanjana / Septham, Praphasri / Phomyu, Wutthikiat / Issaragrisil, Surapol / Pavasant, Prasit

Heliyon

2022 Volume 8, Issue 10, Page(s) e10845

Abstract	Intermittent compressive force influences human periodontal ligament (PDL) cell behavior that facilitates periodontal tissue regeneration. In response to mechanical stimuli, Yes-associated protein (YAP) has been recognized as a mechanosensitive transcriptional activator that regulates cell proliferation and cell fate decisions. This study aimed to investigate whether compressive forces influence cell proliferation and cell fate decisions of human PDL cells via YAP signaling. YAP expression was silenced by shRNA. The effect of YAP on cell proliferation, adipogenesis and osteogenesis of PDL cells under ICF loading were determined. Adipogenic differentiation bias upon ICF loading was confirmed by fourier-transform infrared spectroscopy (FTIR). The results revealed that ICF-induced YAP promotes osteogenesis, but it inhibits adipogenesis in PDL cells. Depletion of YAP results in PDL cells that are irresponsive to ICF and, therefore, the failure of the PDL cells to undergo osteogenic differentiation. This was shown by a significant reduction in calcium deposited in the CF-derived osteoblasts of the YAP-knockdown (YAP-KD) PDL cells. As to control treatment, reduction of YAP promoted adipogenesis, whereas ICF-induced YAP inhibited this mechanism. However, the adipocyte differentiation in YAP-KD cells was not affected upon ICF treatment as the YAP-KD cells still exhibited a better adipogenic differentiation that was unrelated to the ICF. This study demonstrated that, in response to ICF treatment, YAP could be a crucial mechanosensitive transcriptional activator for the regulation of PDL cell behavior through a mechanobiological process. Our results may provide the possibility of facilitating PDL tissue regeneration by manipulation of the Hippo-YAP signaling pathway.
Language	English
Publishing date	2022-10-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2022.e10845
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Article ; Online: Alteration of extracellular matrix proteins in atrophic periodontal ligament of hypofunctional rat molars.

Nan, Daneeya Na / Everts, Vincent / Ferreira, Joao N / Trachoo, Vorapat / Osathanon, Thanaphum / Klincumhom, Nuttha / Pavasant, Prasit

BDJ open

2023 Volume 9, Issue 1, Page(s) 31

Abstract: Objectives: The aim of this study was to investigate the effect of mechanical force on possible dynamic changes of the matrix proteins deposition in the PDL upon in vitro mechanical and in vivo occlusal forces in a rat model with hypofunctional ... ...

Abstract	Objectives: The aim of this study was to investigate the effect of mechanical force on possible dynamic changes of the matrix proteins deposition in the PDL upon in vitro mechanical and in vivo occlusal forces in a rat model with hypofunctional conditions. Materials and methods: Intermittent compressive force (ICF) and shear force (SF) were applied to human periodontal ligament stem cells (PDLSCs). Protein expression of collagen I and POSTN was analyzed by western blot technique. To establish an in vivo model, rat maxillary molars were extracted to facilitate hypofunction of the periodontal ligament (PDL) tissue of the opposing mandibular molar. The mandibles were collected after 4-, 8-, and 12-weeks post-extraction and used for micro-CT and immunohistochemical analysis. Results: ICF and SF increased the synthesis of POSTN by human PDLSCs. Histological changes in the hypofunctional teeth revealed a narrowing of the PDL space, along with a decreased amount of collagen I, POSTN, and laminin in perivascular structures compared to the functional contralateral molars. Conclusion: Our results revealed that loss of occlusal force disrupts deposition of some major matrix proteins in the PDL, underscoring the relevance of mechanical forces in maintaining periodontal tissue homeostasis by modulating ECM composition.
Language	English
Publishing date	2023-07-18
Publishing country	England
Document type	Journal Article
ISSN	2056-807X
ISSN (online)	2056-807X
DOI	10.1038/s41405-023-00155-7
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Article ; Online: Periostin-integrin interaction regulates force-induced TGF-β1 and α-SMA expression by hPDLSCs.

Na Nan, Daneeya / Klincumhom, Nuttha / Trachoo, Vorapat / Everts, Vincent / Ferreira, Joao N / Osathanon, Thanaphum / Pavasant, Prasit

Oral diseases

2023

Abstract: Objective: Periostin (PN), a major matricellular periodontal ligament (PDL) protein, modulates the remodeling of the PDL and bone, especially under mechanical stress. This study investigated the requirement of PN-integrin signaling in force-induced ... ...

Abstract	Objective: Periostin (PN), a major matricellular periodontal ligament (PDL) protein, modulates the remodeling of the PDL and bone, especially under mechanical stress. This study investigated the requirement of PN-integrin signaling in force-induced expression of transforming growth factor-beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) in human PDL stem cells (hPDLSCs). Methods: Cells were stimulated with intermittent compressive force (ICF) using computerized controlled apparatus. Cell migration was examined using in vitro scratch assay. The mRNA expression was examined using real-time polymerase chain reaction. The protein expression was determined using immunofluorescent staining and western blot analysis. Results: Stimulation with ICF for 24 h increased the expression of PN, TGF-β1, and α-SMA, along with increased SMAD2/3 phosphorylation. Knockdown of POSTN (PN gene) decreased the protein levels of TGF-β1 and pSMAD2/3 upon force stimulation. POSTN knockdown of hPDLSCs resulted in delayed cell migration, as determined by a scratch assay. However, migration improved after seeding these knockdown cells on pre-PN-coated surfaces. Further, the knockdown of αVβ5 significantly attenuated the force-induced TGF-β1 expression. Conclusion: Our findings indicate the importance of PN-αVβ5 interactions in ICF-induced TGF-β1 signaling and the expression of α-SMA. Findings support the critical role of PN in maintaining the PDL's tissue integrity and homeostasis.
Language	English
Publishing date	2023-07-19
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	1290529-x
ISSN	1601-0825 ; 1354-523X
ISSN (online)	1601-0825
ISSN	1354-523X
DOI	10.1111/odi.14691
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Article ; Online: Human dental pulp stem cells derived extracellular matrix promotes mineralization via Hippo and Wnt pathways.

Kornsuthisopon, Chatvadee / Nowwarote, Nunthawan / Chansaenroj, Ajjima / Photichailert, Suphalak / Rochanavibhata, Sunisa / Klincumhom, Nuttha / Petit, Stephane / Dingli, Florent / Loew, Damarys / Fournier, Benjamin P J / Osathanon, Thanaphum

Scientific reports

2024 Volume 14, Issue 1, Page(s) 6777

Abstract: Extracellular matrix (ECM) is an intricate structure providing the microenvironment niche that influences stem cell differentiation. This study aimed to investigate the efficacy of decellularized ECM derived from human dental pulp stem cells (dECM_DPSCs) ...

Abstract	Extracellular matrix (ECM) is an intricate structure providing the microenvironment niche that influences stem cell differentiation. This study aimed to investigate the efficacy of decellularized ECM derived from human dental pulp stem cells (dECM_DPSCs) and gingival-derived mesenchymal stem cells (dECM_GSCs) as an inductive scaffold for osteogenic differentiation of GSCs. The proteomic analysis demonstrated that common and signature matrisome proteins from dECM_DPSCs and dECM_GSCs were related to osteogenesis/osteogenic differentiation. RNA sequencing data from GSCs reseeded on dECM_DPSCs revealed that dECM_DPSCs upregulated genes related to the Hippo and Wnt signaling pathways in GSCs. In the inhibitor experiments, results revealed that dECM_DPSCs superiorly promoted GSCs osteogenic differentiation, mainly mediated through Hippo and Wnt signaling. The present study emphasizes the promising translational application of dECM_DPSCs as a bio-scaffold rich in favorable regenerative microenvironment for tissue engineering.
MeSH term(s)	Humans ; Osteogenesis/genetics ; Wnt Signaling Pathway ; Proteomics ; Dental Pulp ; Extracellular Matrix/metabolism ; Cell Differentiation ; Stem Cells/metabolism ; Cell Proliferation ; Cells, Cultured
Language	English
Publishing date	2024-03-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-56845-1
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Article ; Online: Shear Stress Enhances the Paracrine-Mediated Immunoregulatory Function of Human Periodontal Ligament Stem Cells via the ERK Signalling Pathway.

Suwittayarak, Ravipha / Klincumhom, Nuttha / Ngaokrajang, Utapin / Namangkalakul, Worachat / Ferreira, João N / Pavasant, Prasit / Osathanon, Thanaphum

International journal of molecular sciences

2022 Volume 23, Issue 13

Abstract: Relevant immunomodulatory effects have been proposed following allogeneic cell-based therapy with human periodontal ligament stem cells (hPDLSCs). This study aimed to examine the influence of shear stress on the immunosuppressive capacity of hPDLSCs. ... ...

Abstract	Relevant immunomodulatory effects have been proposed following allogeneic cell-based therapy with human periodontal ligament stem cells (hPDLSCs). This study aimed to examine the influence of shear stress on the immunosuppressive capacity of hPDLSCs. Cells were subjected to shear stress at different magnitudes (0.5, 5 and 10 dyn/cm2). The expression of immunosuppressive markers was evaluated in shear stress-induced hPDLSCs using qRT-PCR, western blot, enzyme activity and enzyme-linked immunosorbent assays. The effects of a shear stress-derived condition medium (SS-CM) on T cell proliferation were examined using a resazurin assay. Treg differentiation was investigated using qRT-PCR and flow cytometry analysis. Our results revealed that shear stress increased mRNA expression of
MeSH term(s)	Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Humans ; Kynurenine/metabolism ; Osteogenesis ; Periodontal Ligament ; Stem Cells/metabolism
Chemical Substances	Kynurenine (343-65-7)
Language	English
Publishing date	2022-06-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23137119
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Article ; Online: Strategies for Developing Functional Secretory Epithelia from Porcine Salivary Gland Explant Outgrowth Culture Models.

Urkasemsin, Ganokon / Castillo, Phoebe / Rungarunlert, Sasitorn / Klincumhom, Nuttha / Ferreira, Joao N

Biomolecules

2019 Volume 9, Issue 11

Abstract: Research efforts have been made to develop human salivary gland (SG) secretory epithelia for transplantation in patients with SG hypofunction and dry mouth (xerostomia). However, the limited availability of human biopsies hinders the generation of ... ...

Abstract	Research efforts have been made to develop human salivary gland (SG) secretory epithelia for transplantation in patients with SG hypofunction and dry mouth (xerostomia). However, the limited availability of human biopsies hinders the generation of sufficient cell numbers for epithelia formation and regeneration. Porcine SG have several similarities to their human counterparts, hence could replace human cells in SG modelling studies in vitro. Our study aims to establish porcine SG explant outgrowth models to generate functional secretory epithelia for regeneration purposes to rescue hyposalivation. Cells were isolated and expanded from porcine submandibular and parotid gland explants. Flow cytometry, immunocytochemistry, and gene arrays were performed to assess proliferation, standard mesenchymal stem cell, and putative SG epithelial stem/progenitor cell markers. Epithelial differentiation was induced and different SG-specific markers investigated. Functional assays upon neurostimulation determined α-amylase activity, trans-epithelial electrical resistance, and calcium influx. Primary cells exhibited SG epithelial progenitors and proliferation markers. After differentiation, SG markers were abundantly expressed resembling epithelial lineages (E-cadherin, Krt5, Krt14), and myoepithelial (α-smooth muscle actin) and neuronal (β3-tubulin, Chrm3) compartments. Differentiated cells from submandibular gland explant models displayed significantly greater proliferation, number of epithelial progenitors, amylase activity, and epithelial barrier function when compared to parotid gland models. Intracellular calcium was mobilized upon cholinergic and adrenergic neurostimulation. In summary, this study highlights new strategies to develop secretory epithelia from porcine SG explants, suitable for future proof-of-concept SG regeneration studies, as well as for testing novel muscarinic agonists and other biomolecules for dry mouth.
MeSH term(s)	Animals ; Cell Differentiation ; Epithelium ; Salivary Glands ; Swine ; Tissue Engineering
Language	English
Publishing date	2019-10-25
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom9110657
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Article ; Online: One-step genetic correction of hemoglobin E/beta-thalassemia patient-derived iPSCs by the CRISPR/Cas9 system.

Wattanapanitch, Methichit / Damkham, Nattaya / Potirat, Ponthip / Trakarnsanga, Kongtana / Janan, Montira / U-Pratya, Yaowalak / Kheolamai, Pakpoom / Klincumhom, Nuttha / Issaragrisil, Surapol

Stem cell research & therapy

2018 Volume 9, Issue 1, Page(s) 46

Abstract: Background: Thalassemia is the most common genetic disease worldwide; those with severe disease require lifelong blood transfusion and iron chelation therapy. The definitive cure for thalassemia is allogeneic hematopoietic stem cell transplantation, ... ...

Abstract	Background: Thalassemia is the most common genetic disease worldwide; those with severe disease require lifelong blood transfusion and iron chelation therapy. The definitive cure for thalassemia is allogeneic hematopoietic stem cell transplantation, which is limited due to lack of HLA-matched donors and the risk of post-transplant complications. Induced pluripotent stem cell (iPSC) technology offers prospects for autologous cell-based therapy which could avoid the immunological problems. We now report genetic correction of the beta hemoglobin (HBB) gene in iPSCs derived from a patient with a double heterozygote for hemoglobin E and β-thalassemia (HbE/β-thalassemia), the most common thalassemia syndrome in Thailand and Southeast Asia. Methods: We used the CRISPR/Cas9 system to target the hemoglobin E mutation from one allele of the HBB gene by homology-directed repair with a single-stranded DNA oligonucleotide template. DNA sequences of the corrected iPSCs were validated by Sanger sequencing. The corrected clones were differentiated into hematopoietic progenitor and erythroid cells to confirm their multilineage differentiation potential and hemoglobin expression. Results: The hemoglobin E mutation of HbE/β-thalassemia iPSCs was seamlessly corrected by the CRISPR/Cas9 system. The corrected clones were differentiated into hematopoietic progenitor cells under feeder-free and OP9 coculture systems. These progenitor cells were further expanded in erythroid liquid culture system and developed into erythroid cells that expressed mature HBB gene and HBB protein. Conclusions: Our study provides a strategy to correct hemoglobin E mutation in one step and these corrected iPSCs can be differentiated into hematopoietic stem cells to be used for autologous transplantation in patients with HbE/β-thalassemia in the future.
MeSH term(s)	Autografts ; CRISPR-Cas Systems ; Female ; Gene Editing ; Hemoglobin E/genetics ; Hemoglobin E/metabolism ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Male ; Mutation ; Stem Cell Transplantation ; beta-Thalassemia/genetics ; beta-Thalassemia/metabolism ; beta-Thalassemia/therapy
Chemical Substances	Hemoglobin E (9034-61-1)
Language	English
Publishing date	2018-02-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2548671-8
ISSN	1757-6512 ; 1757-6512
ISSN (online)	1757-6512
ISSN	1757-6512
DOI	10.1186/s13287-018-0779-3
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Article ; Online: Enhanced human mesenchymal stem cell survival under oxidative stress by overexpression of secreted frizzled-related protein 2 gene.

Pomduk, Kanjana / Kheolamai, Pakpoom / U-Pratya, Yaowalak / Wattanapanitch, Methichit / Klincumhom, Nuttha / Issaragrisil, Surapol

Annals of hematology

2015 Volume 94, Issue 2, Page(s) 319–327

Abstract: Human mesenchymal stem cells (hMSCs) have been used to improve engraftment and to treat graft versus host disease following allogeneic hematopoietic stem cell transplantation. However, oxidative stress presented in the microenvironment can damage the ... ...

Abstract	Human mesenchymal stem cells (hMSCs) have been used to improve engraftment and to treat graft versus host disease following allogeneic hematopoietic stem cell transplantation. However, oxidative stress presented in the microenvironment can damage the transplanted hMSCs and therefore reduce their survival in target organs. We investigated how to enhance the survival of hMSCs under oxidative stress by overexpressing secreted frizzled-related protein 2 (sFRP2) gene in bone marrow-derived hMSCs and umbilical cord-derived hMSCs. The survival and characteristics of those sFRP2-overexpressing hMSCs (sFRP2-BM-hMSCs and sFRP2-UC-hMSCs) were studied compared with non-transduced hMSCs. We found that the percentages of viable cells in culture of sFRP2-BM-hMSCs and sFRP2-UC-hMSCs in the absence or presence of 0.75 mM H2O2 were significantly higher than those of their non-transduced counterparts. The overexpression of sFRP2 gene did not affect the characteristics of hMSCs regarding their morphology, surface marker expression, and differentiation potential. Our study suggests that overexpression of sFRP2 gene in hMSCs might improve the therapeutic effectiveness of hMSC transplantation.
MeSH term(s)	Amnion/cytology ; Cell Survival/drug effects ; Cell Survival/genetics ; Cells, Cultured ; Female ; Fetal Blood/cytology ; Flow Cytometry ; Gene Expression ; Humans ; Hydrogen Peroxide/pharmacology ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mesenchymal Stromal Cells/metabolism ; Oxidants/pharmacology ; Oxidative Stress ; Placenta/cytology ; Pregnancy ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection
Chemical Substances	Membrane Proteins ; Oxidants ; SFRP2 protein, human ; Hydrogen Peroxide (BBX060AN9V)
Language	English
Publishing date	2015-02
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1064950-5
ISSN	1432-0584 ; 0939-5555 ; 0945-8077
ISSN (online)	1432-0584
ISSN	0939-5555 ; 0945-8077
DOI	10.1007/s00277-014-2210-1
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Article ; Online: Selective TGF-β1/ALK inhibitor improves neuronal differentiation of mouse embryonic stem cells.

Klincumhom, Nuttha / Tharasanit, Theerawat / Thongkittidilok, Chommanart / Tiptanavattana, Narong / Rungarunlert, Sasitorn / Dinnyés, András / Techakumphu, Mongkol

Neuroscience letters

2014 Volume 578, Page(s) 1–6

Abstract: The transforming growth factor-β1 (TGF-β1), a polypeptide member of the TGF-β superfamily, has myriad cellular functions, including cell fate differentiation. We hypothesized that suppression of TGF-β1 signaling would improve the efficacy of neuronal ... ...

Abstract	The transforming growth factor-β1 (TGF-β1), a polypeptide member of the TGF-β superfamily, has myriad cellular functions, including cell fate differentiation. We hypothesized that suppression of TGF-β1 signaling would improve the efficacy of neuronal differentiation during embryoid body (EB) development. In this study, mouse embryonic stem cells (ESCs) were allowed to differentiate into their neuronal lineage, both with, and without the TGF-β1 inhibitor (A83-01). After 8 days of EB suspension culture, the samples were examined by morphological analysis, immunocytochemistry and immunohistochemistry with pluripotent (Oct4, Sox2) and neuronal specific markers (Pax6, NeuN). The alteration of gene expressions during EB development was determined by quantitative RT-PCR. Our results revealed that the TGF-β1/ALK inhibitor potentially suppressed pluripotent gene (Oct4) during a rapidly up-regulation of neuronal associated genes including Sox1 and MAP2. Strikingly, during EB development, the expression of GFAP, the astrocyte specific gene, remarkably decreased compared to the non-treated control. This strategy demonstrated the beneficial function of TGF-β1/ALK inhibitor that rapidly and uniformly drives cell fate alteration from pluripotent state toward neuronal lineages.
MeSH term(s)	Activin Receptors, Type I/antagonists & inhibitors ; Animals ; Cell Differentiation/drug effects ; Cell Differentiation/genetics ; Embryoid Bodies ; Embryonic Stem Cells/drug effects ; Embryonic Stem Cells/metabolism ; Embryonic Stem Cells/physiology ; Mice ; Neural Stem Cells/drug effects ; Neural Stem Cells/metabolism ; Neural Stem Cells/physiology ; Neurogenesis/drug effects ; Neuroglia/metabolism ; Neuroglia/physiology ; Protein-Serine-Threonine Kinases/antagonists & inhibitors ; Pyrazoles/pharmacology ; Receptors, Transforming Growth Factor beta/antagonists & inhibitors ; Signal Transduction ; Thiocarbamates/pharmacology ; Thiosemicarbazones ; Transforming Growth Factor beta1/antagonists & inhibitors ; Transforming Growth Factor beta1/metabolism
Chemical Substances	A-83-01 ; Pyrazoles ; Receptors, Transforming Growth Factor beta ; Thiocarbamates ; Thiosemicarbazones ; Transforming Growth Factor beta1 ; TGF-beta type I receptor (EC 2.7.1.11) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; Activin Receptors, Type I (EC 2.7.11.30)
Language	English
Publishing date	2014-08-22
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	194929-9
ISSN	1872-7972 ; 0304-3940
ISSN (online)	1872-7972
ISSN	0304-3940
DOI	10.1016/j.neulet.2014.06.001
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