Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 50
Filter
Add more filters










Publication year range
1.
Sci Rep ; 14(1): 15325, 2024 07 03.
Article in English | MEDLINE | ID: mdl-38961140

ABSTRACT

This study was performed to segment the urinary system as the basis for diagnosing urinary system diseases on non-contrast computed tomography (CT). This study was conducted with images obtained between January 2016 and December 2020. During the study period, non-contrast abdominopelvic CT scans of patients and diagnosed and treated with urinary stones at the emergency departments of two institutions were collected. Region of interest extraction was first performed, and urinary system segmentation was performed using a modified U-Net. Thereafter, fivefold cross-validation was performed to evaluate the robustness of the model performance. In fivefold cross-validation results of the segmentation of the urinary system, the average dice coefficient was 0.8673, and the dice coefficients for each class (kidney, ureter, and urinary bladder) were 0.9651, 0.7172, and 0.9196, respectively. In the test dataset, the average dice coefficient of best performing model in fivefold cross validation for whole urinary system was 0.8623, and the dice coefficients for each class (kidney, ureter, and urinary bladder) were 0.9613, 0.7225, and 0.9032, respectively. The segmentation of the urinary system using the modified U-Net proposed in this study could be the basis for the detection of kidney, ureter, and urinary bladder lesions, such as stones and tumours, through machine learning.


Subject(s)
Kidney , Tomography, X-Ray Computed , Ureter , Urinary Bladder , Humans , Tomography, X-Ray Computed/methods , Urinary Bladder/diagnostic imaging , Ureter/diagnostic imaging , Kidney/diagnostic imaging , Female , Male , Middle Aged , Adult , Aged , Image Processing, Computer-Assisted/methods , Neural Networks, Computer
2.
Animals (Basel) ; 14(11)2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38891734

ABSTRACT

A 2-year-old, intact female Pomeranian presented with bilateral forelimb lameness, characterized by the olecranon making contact with the ground. The patient experienced two separate incidents of falling, occurring four and three weeks before admission, respectively. Following each episode, non-weight-bearing lameness was initially observed in the left forelimb, followed by the development of crouch gait. Based on the physical examination, radiographic, and ultrasonographic findings, bilateral triceps brachii tendon disruption was diagnosed. Intraoperatively, excessive granulation tissue at the distal end of the tendon was excised. The footprint region of each triceps brachii tendon was decorticated with a high-speed burr until bleeding was observed. The triceps brachii tendon was reattached to completely cover its footprint on the olecranon using the Krackow suture technique. This method involves anchoring the suture through bone tunnels in the ulna. Trans-articular external skeletal fixation was applied to both forelimbs to immobile and stabilize the elbow joints for nine weeks. Subsequently, the dog gradually increased its walking activities while on a leash over a six-week period. At the three-year follow-up, the patient exhibited improved forelimb function and maintained a normal gait without signs of lameness. Suture-mediated anatomic footprint repair proved useful in this single case and may be an effective surgical alternative for the management of chronic triceps brachii tendon disruption in dogs.

3.
Curr Issues Mol Biol ; 45(10): 8126-8137, 2023 Oct 06.
Article in English | MEDLINE | ID: mdl-37886956

ABSTRACT

This study investigated the effects of silibinin, derived from milk thistle (Silybum marianum), on lipopolysaccharide (LPS)-induced morphological changes in mouse macrophages. Silibinin was treated at various doses and time points to assess its effects on macrophage activation, including morphological changes and phagocytosis. Silibinin effectively inhibited LPS-induced pseudopodia formation and size increase, while unstimulated cells remained round. Silibinin's impact on phagocytosis was dose- and time-dependent, showing a decrease. We explored its mechanism of action on kinases using a MAPK array. Among the three MAPK family members tested, silibinin had a limited effect on JNK and p38 but significantly inhibited ERK1/2 and related RSK1/2. Silibinin also inhibited MKK6, AKT3, MSK2, p70S6K, and GSK-3ß. These findings highlight silibinin's potent inhibitory effects on phagocytosis and morphological changes in macrophages. We suggest its potential as an anti-inflammatory agent due to its ability to target key inflammatory pathways involving ERK1/2 and related kinases. Overall, this study demonstrates the promising therapeutic properties of silibinin in modulating macrophage function and inflammation.

4.
Cell Death Dis ; 12(11): 1013, 2021 10 28.
Article in English | MEDLINE | ID: mdl-34711817

ABSTRACT

ABSTRCT: Ephexin1 was reported to be highly upregulated by oncogenic Ras, but the functional consequences of this remain poorly understood. Here, we show that Ephexin1 is highly expressed in colorectal cancer (CRC) and lung cancer (LC) patient tissues. Knockdown of Ephexin1 markedly inhibited the cell growth of CRC and LC cells with oncogenic Ras mutations. Ephexin1 contributes to the positive regulation of Ras-mediated downstream target genes and promotes Ras-induced skin tumorigenesis. Mechanically, Akt phosphorylates Ephexin1 at Ser16 and Ser18 (pSer16/18) and pSer16/18 Ephexin1 then interacts with oncogenic K-Ras to promote downstream MAPK signaling, facilitating tumorigenesis. Furthermore, pSer16/18 Ephexin1 is associated with both an increased tumor grade and metastatic cases of CRC and LC, and those that highly express pSer16/18 exhibit poor overall survival rates. These data indicate that Ephexin1 plays a critical role in the Ras-mediated CRC and LC and pSer16/18 Ephexin1 might be an effective therapeutic target for CRC and LC.


Subject(s)
Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Guanine Nucleotide Exchange Factors/metabolism , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Oncogenes , Proto-Oncogene Proteins c-akt/metabolism , ras Proteins/metabolism , Amino Acid Sequence , Animals , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Guanine Nucleotide Exchange Factors/chemistry , Guanine Nucleotide Exchange Factors/genetics , HEK293 Cells , Humans , MAP Kinase Signaling System , Male , Mice, Inbred BALB C , Mice, Nude , Models, Biological , Phosphorylation , Phosphoserine/metabolism , Prognosis , Protein Binding , Protein Domains , RNA, Messenger/genetics , RNA, Messenger/metabolism , Up-Regulation
5.
Carcinogenesis ; 38(12): 1228-1240, 2017 12 07.
Article in English | MEDLINE | ID: mdl-29040381

ABSTRACT

The Wilms' tumor 1 (WT1) gene is believed to act as a canonical tumor suppressor. However, it has also been reported to function as an oncogene. Germline WT1 deletion is associated with Wilms' tumor, and exogenous WT1 cDNA introduction into cells induces the transcriptional suppression of its oncogenic target genes. In contrast, high WT1 expression is associated with poor prognosis in patients with various cancers. Why WT1 acts as a tumor suppressor under certain conditions but as an oncogene under other conditions is unknown. Here, we report that CUG initiation site for WT1 protein synthesis (CUG)-translated WT1 (cugWT1), an N-terminally extended form of canonical AUG initiation site for WT1 protein synthesis (AUG)-translated WT1 (augWT1), was overexpressed in most cancer cell lines and cancer tissues and functioned as an oncogene, whereas the classical augWT1 acted as a tumor suppressor as reported previously and inhibited the function of cugWT1. Translation of cugWT1 is initiated from a CUG codon upstream and in-frame with the coding region of augWT1. cugWT1 induced cell transformation and increased the gene expression of c-myc, bcl-2 and egfr, whereas overexpression of augWT1 repressed colony formation of cancer cells and inhibited the expression of the same target genes by recruiting histone deacetylase 1 (HDAC1). In addition, we found that protein kinase B (AKT)-phosphorylated cugWT1 on Ser62 and protected cugWT1 from proteasomal degradation induced by the F-box/WD repeat-containing protein 8 (FBXW8). These results provide an important breakthrough in the field of cancer biology and contribute significantly to the resolution of the chameleon function of WT1.


Subject(s)
Genes, Wilms Tumor , Oncogenes/genetics , Protein Biosynthesis/genetics , Transcription Initiation Site , WT1 Proteins/genetics , Animals , Cell Line, Tumor , Female , Heterografts , Humans , Male , Mice , Mice, Nude
6.
Korean J Physiol Pharmacol ; 21(1): 117-124, 2017 Jan.
Article in English | MEDLINE | ID: mdl-28066148

ABSTRACT

The present study aimed to show that pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-1ß] synergistically induce the production of nitric oxide (NO) production in mouse mesangial cells, which play an important role in inflammatory glomerular injury. We also found that co-treatment with cytokines at low doses (TNF-α; 5 ng/ml, IFN-γ; 5 ng/ml, and IL-1ß; 1.25 U/ml) synergistically induced NO production, whereas treatment with each cytokine alone did not increase NO production at doses up to 100 ng/ml or 50 U/ml. Silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), attenuates cytokine mixture (TNF-α, IFN-γ, and IL-1ß)-induced NO production. Western blot and RT-PCR analyses showed that silymarin inhibits inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner. Silymarin also inhibited extracellular signal-regulated protein kinase-1 and -2 (ERK1/2) phosphorylation. Collectively, we have demonstrated that silymarin inhibits NO production in mouse mesangial cells, and may act as a useful anti-inflammatory agent.

7.
Sci Rep ; 6: 35733, 2016 10 24.
Article in English | MEDLINE | ID: mdl-27775004

ABSTRACT

Here, we report a high performance biosensor based on (i) a Cu2+-DNA/MoS2 hybrid structure and (ii) a field effect transistor, which we refer to as a bio-FET, presenting a high sensitivity of 1.7 × 103 A/A. This high sensitivity was achieved by using a DNA nanostructure with copper ions (Cu2+) that induced a positive polarity in the DNA (receptor). This strategy improved the detecting ability for doxorubicin-like molecules (target) that have a negative polarity. Very short distance between the biomolecules and the sensor surface was obtained without using a dielectric layer, contributing to the high sensitivity. We first investigated the effect of doxorubicin on DNA/MoS2 and Cu2+-DNA/MoS2 nanostructures using Raman spectroscopy and Kelvin force probe microscopy. Then, we analyzed the sensing mechanism and performance in DNA/MoS2- and Cu2+-DNA/MoS2-based bio-FETs by electrical measurements (ID-VG at various VD) for various concentrations of doxorubicin. Finally, successful operation of the Cu2+-DNA/MoS2 bio-FET was demonstrated for six cycles (each cycle consisted of four steps: 2 preparation steps, a sensing step, and an erasing step) with different doxorubicin concentrations. The bio-FET showed excellent reusability, which has not been achieved previously in 2D biosensors.

8.
Korean J Physiol Pharmacol ; 19(3): 211-8, 2015 May.
Article in English | MEDLINE | ID: mdl-25954125

ABSTRACT

The present study showed that silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), inhibited lipopolysaccharide (LPS)-induced morphological changes in the mouse RAW264.7 macrophage cell line. We also showed that silymarin inhibited the nuclear translocation and transactivation activities of nuclear factor-kappa B (NF-κB), which is important for macrophage activation-associated changes in cell morphology and gene expression of inflammatory cytokines. BAY-11-7085, an NF-κB inhibitor, abrogated LPS-induced morphological changes and NO production, similar to silymarin. Treatment of RAW264.7 cells with silymarin also inhibited LPS-stimulated activation of mitogen-activated protein kinases (MAPKs). Collectively, these experiments demonstrated that silymarin inhibited LPS-induced morphological changes in the RAW264.7 mouse macrophage cell line. Our findings indicated that the most likely mechanism underlying this biological effect involved inhibition of the MAPK pathway and NF-κB activity. Inhibition of these activities by silymarin is a potentially useful strategy for the treatment of inflammation because of the critical roles played by MAPK and NF-κB in mediating inflammatory responses in macrophages.

9.
Biomol Ther (Seoul) ; 22(4): 282-7, 2014 Jul.
Article in English | MEDLINE | ID: mdl-25143805

ABSTRACT

We show that silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), inhibits cytokine mixture (CM: TNF-α, IFN-γ, and IL-1ß)-induced production of nitric oxide (NO) in the pancreatic beta cell line MIN6N8a. Immunostaining and Western blot analysis showed that silymarin inhibits iNOS gene expression. RT-PCR showed that silymarin inhibits iNOS gene expression in a dose-dependent manner. We also showed that silymarin inhibits extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) phosphorylation. A MEK1 inhibitor abrogated CM-induced nitrite production, similar to silymarin. Treatment of MIN6N8a cells with silymarin also inhibited CM-stimulated activation of NF-κB, which is important for iNOS transcription. Collectively, we demonstrate that silymarin inhibits NO production in pancreatic beta cells, and silymarin may represent a useful anti-diabetic agent.

10.
Acta Histochem ; 116(4): 551-8, 2014 May.
Article in English | MEDLINE | ID: mdl-24360190

ABSTRACT

The START domain-containing 6 (StarD6) was originally reported to play a role during male germ cell maturation. We have since reported on StarD6 in the developing hypothyroid rat brain. Therefore, we investigated qualitative and quantitative changes of StarD6 in the aging rat brain and testes of male Sprague-Dawley rats. Serum testosterone levels decreased with aging and total protein levels of StarD6 in the testes decreased. While the immunolocalization of StarD6 in the spermatocytes decreased, cytoplasmic localization appeared in the aged testes. Compared with young rats, aged rats showed decreased StarD6 in the cerebrum and cerebellum without changes in immunolocalization in the cortical neurons of the cerebral cortex and Purkinje cells of the cerebellar cortex. Aged rats also showed increases in StarD6 in the hippocampus with changes in its immunolocalization from the Stratum pyramidale to the Stratum radiatum and Stratum lacunosum-moleculare. Taken together, StarD6 decreased with aging in the testes, which implies that StarD6 might play a role in impaired spermatogenesis in the aged rat. StarD6 decreased in the cerebrum and the cerebellum, but slightly increased in the hippocampus, which suggests that StarD6 might also play a role for neurosteroidogenesis in the hippocampus of aged rats.


Subject(s)
Brain/metabolism , Carrier Proteins/metabolism , Lipid Metabolism/physiology , Testis/metabolism , Aging , Animals , Lipids , Male , Neurons/metabolism , Rats, Sprague-Dawley
11.
Biomol Ther (Seoul) ; 21(4): 258-63, 2013 Jul 30.
Article in English | MEDLINE | ID: mdl-24244809

ABSTRACT

We demonstrate herein that silibinin, a polyphenolic flavonoid compound isolated from milk thistle (Silybum marianum), inhibits LPS-induced activation of macrophages and production of nitric oxide (NO) in RAW 264.7 cells. Western blot analysis showed silibinin inhibits iNOS gene expression. RT-PCR showed that silibinin inhibits iNOS, TNF-α, and IL1ß. We also showed that silibinin strongly inhibits p38 MAPK phosphorylation, whereas the ERK1/2 and JNK pathways are not inhibited. The p38 MAPK inhibitor abrogated the LPS-induced nitrite production, whereas the MEK-1 inhibitor did not affect the nitrite production. A molecular modeling study proposed a binding pose for silibinin targeting the ATP binding site of p38 MAPK (1OUK). Collectively, this series of experiments indicates that silibinin inhibits macrophage activation by blocking p38 MAPK signaling.

12.
Arch Orthop Trauma Surg ; 133(12): 1665-8, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23995551

ABSTRACT

Varus posteromedial rotatory instability refers to one of the complex elbow fracture-dislocation caused by anteromedial coronoid fracture with disruption of lateral collateral ligament (LCL). Recent clinical and biomechanical studies have demonstrated that this unstable complex injury resulted in incongruence of joint, which could lead to early posttraumatic arthritis. With reports of poor result after conservative treatment, surgical treatment including anteromedial fixation and LCL repair has been strongly recommended to achieve stable joint. This case series describes three patients with anteromedial coronoid fracture who were managed conservatively with excellent outcomes. This report suggests that anteromedial coronoid fracture associated with posteromedial rotatory instability might be treated using conservative treatment in selective cases when anteromedial coronoid fracture is minimally displaced and there is no evidence of elbow subluxation.


Subject(s)
Elbow Injuries , Joint Instability/diagnostic imaging , Ulna Fractures/diagnostic imaging , Adult , Casts, Surgical , Collateral Ligaments/injuries , Follow-Up Studies , Humans , Joint Dislocations/diagnostic imaging , Joint Dislocations/therapy , Joint Instability/therapy , Male , Middle Aged , Radiography , Ulna Fractures/therapy
13.
Korean J Physiol Pharmacol ; 17(4): 315-20, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23946691

ABSTRACT

Here, we show that radicicol, a fungal antibiotic, resulted in marked inhibition of inducible nitric oxide synthase (iNOS) transcription by the pancreatic beta cell line MIN6N8a in response to cytokine mixture (CM: TNF-α, IFN-γ, and IL-1ß). Treatment of MIN6N8a cells with radicicol inhibited CM-stimulated activation of NF-κB/Rel, which plays a critical role in iNOS transcription, in a dose-related manner. Nitrite production in the presence of PD98059, a specific inhibitor of the extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) pathway, was dramatically diminished, suggesting that the ERK1/2 pathway is involved in CM-induced iNOS expression. In contrast, SB203580, a specific inhibitor of p38, had no effect on nitrite generation. Collectively, this series of experiments indicates that radicicol inhibits iNOS gene expression by blocking ERK1/2 signaling. Due to the critical role that NO release plays in mediating destruction of pancreatic beta cells, the inhibitory effects of radicicol on iNOS expression suggest that radicicol may represent a useful anti-diabetic activity.

14.
J Clin Invest ; 2013 Jul 01.
Article in English | MEDLINE | ID: mdl-23863623

ABSTRACT

Aberrant expression of apurinic-apyrimidinic endonuclease-1 (APEX1) has been reported in numerous human solid tumors and is positively correlated with cancer progression; however, the role of APEX1 in tumor progression is poorly defined. Here, we show that APEX1 contributes to aggressive colon cancer behavior and functions as an upstream activator in the Jagged1/Notch signaling pathway. APEX1 overexpression or knockdown in human colon cancer cell lines induced profound changes in malignant properties such as cell proliferation, anchorage-independent growth, migration, invasion, and angiogenesis in vitro and in tumor formation and metastasis in mouse xenograft models. These oncogenic effects of APEX1 were mediated by the upregulation of Jagged1, a major Notch ligand. Furthermore, APEX1 expression was associated with Jagged1 in various colon cancer cell lines and in tissues from colon cancer patients. This finding identifies APEX1 as a positive regulator of Jagged1/Notch activity and suggests that it is a potential therapeutic target in colon cancers that exhibit high levels of Jagged1/Notch signaling.

15.
Korean J Physiol Pharmacol ; 16(6): 431-6, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23269906

ABSTRACT

Dioscorea species continue to be used in traditional Chinese medicine, and represent a major source of steroid precursors for conventional medicine. In the previous study, We isolated glycoprotein (GDB) from Dioscorea batatas, characterized, and demonstrated immunostimulating activity in C57BL/6 mice. The aim of this study was to investigate the mechanism whereby GDB activates macrophages. Macrophages activation by GDB was investigated by analyzing the effects of GDB on nitric oxide (NO) production, iNOS expression, mitogen activated protein kinase (MAPK) phosphorylation, and transcription factor activation. In the presence of IFN-γ, GDB strongly stimulated macrophages to express iNOS and produce NO. Furthermore, the activation of p38 was synergistically induced by GDB plus IFN-γ , but SB203580 (a p38 inhibitor) inhibited GDB plus IFN-γ-induced p38 activation. This study indicates that GDB is an important activator of macrophages. Furthermore, due to the critical role that macrophage activation plays in innate immune response, the activation effects of GDB on macrophages suggest that GDB may be a useful immunopotentiating agent.

16.
Korean J Physiol Pharmacol ; 15(2): 101-6, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21660150

ABSTRACT

We demonstrate that glycoprotein isolated from Dioscorea batatas (GDB) has immunostimulatory effects including macrophage activation. Analysis of infiltration of inflammatory cells into peritoneal cavity showed GDB treatment significantly increased the recruitment of macrophages, lymphocytes, neutrophils, and monocytes into the peritoneal cavity. Treatment of spleen cells isolated from C57BL/6 mice with GDB significantly increased the proliferation of B cells and T cells induced by LPS and ConA, respectively. Treatment with GDB significantly increased the cytolytic capacity of NK cells and macrophages against YAC-1 and B16 cells, respectively. In order to further confirm and investigate the mechanism of GDB on macrophage activation, we analyzed the effects of GDB on the cytokine expression including iNOS, IL-1ß, and TNF-α in mouse macrophage cell line, RAW 264.7 cells. RT-PCR and ELISA showed that GDB increased the expression of IL-1ß, and TNF-α, whereas iNOS was not induced by GDB. Collectively, this series of experiments indicates that GDB stimulates immune system including macrophage activation.

17.
Free Radic Res ; 45(6): 728-34, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21473738

ABSTRACT

p53 plays a major role in apoptosis through activation of pro-apoptotic gene Bax. It also regulates apurinic/apyrimidinic endonuclease (APE) expression in the base excision repair pathway against oxidative DNA damages. This study investigated whether p53-dependent apoptosis is correlated with APE using an experimental rat model of hydronephrosis. Hydronephrosis was induced by partial ligation of the right ureter. Animals were sacrificed on scheduled time after unilateral ureteral obstruction and the expression of 8-OHdG, γ-H2AX, apoptotic proteins and APE was determined. The accumulated p53 activated Bax and caspase-3 7 days after hydronephrosis induction and the resulting high levels of p53-dependent apoptotic proteins and γ-H2AX tended to decrease APE. The intensities of 8-OHdG and caspase-3 immunolocalization significantly increased in obstructed kidneys than in sham-operated kidneys, although APE immunoreactivity increased after hydronephrosis induction. These results suggest that oxidative DNA damages in obstructed kidneys may trigger p53-dependent apoptosis through repression of APE.


Subject(s)
DNA-(Apurinic or Apyrimidinic Site) Lyase/biosynthesis , Hydronephrosis/pathology , Kidney/pathology , Tumor Suppressor Protein p53/metabolism , 8-Hydroxy-2'-Deoxyguanosine , Animals , Apoptosis , Apoptosis Regulatory Proteins/metabolism , Caspase 3/metabolism , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/metabolism , Enzyme Repression , Hydronephrosis/metabolism , Kidney/metabolism , Male , Oxidation-Reduction , Oxidative Stress , Rats , Rats, Sprague-Dawley
18.
Toxicol Res ; 27(2): 71-6, 2011 Jun.
Article in English | MEDLINE | ID: mdl-24278554

ABSTRACT

We demonstrate that baicalein, a bioactive flavonoid originally isolated from Scutellaria baicalensis, inhibits LPS-induced expression of iNOS gene in RAW 264.7 cells. Treatment of peritoneal macrophages and RAW 264.7 cells with baicalein inhibited LPS-stimulated nitric oxide production in a dose-related manner. Immunohistochemical staining of iNOS and RT-PCR analysis showed that the decrease of NO was due to the inhibition of iNOS gene expression in RAW 264.7 cells. Immunostaining of p65, EMSA, and reporter gene assay showed that baicalein inhibited NF-κB nuclear translocation, DNA binding, and transcriptional activation, respectively. Collectively, these series of experiments indicate that baicalein inhibits iNOS gene expression by blocking NF-κB nuclear translocation. Due to the critical role that NO release plays in mediating inflammatory responses, the inhibitory effects of baicalein on iNOS suggest that baicalein may represent a useful anti-inflammatory agent.

19.
Toxicol Res ; 27(3): 167-72, 2011 Sep.
Article in English | MEDLINE | ID: mdl-24278568

ABSTRACT

We demonstrate that glycoprotein isolated from Dioscorea batatas (GDB) activates macrophage function. Analysis of the infiltration of macrophages into peritoneal cavity showed GDB treatment significantly increased the recruitment of macrophages into the peritoneal cavity. In order to further confirm and investigate the mechanism of GDB on macrophage activation, we analyzed the effects of GDB on the cytokine expression including IL-1ß, TNF-α, and IL-6 in mouse peritoneal macrophages. GDB increased the expression of IL-1ß, TNF-α, and IL-6. Cytokine induction by GDB was further confirmed by RT-PCR and ELISA in mouse macrophage cell line, RAW264.7 cells. Treatment of RAW264.7 cells with GDB produced strong induction of NF-κB DNA binding and MAPK phosphorylation, markers for macrophage activation and important factors for cytokine gene expression. Collectively, this series of experiments indicates that GDB stimulates macrophage activation.

20.
Stem Cells ; 28(12): 2141-50, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20945330

ABSTRACT

Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by transduction of reprogramming factors, including Oct4, Sox2, Klf4, and c-Myc. A coordinated network of these factors was suggested to confer a pluripotency of iPSCs. Together with Oct4, Sox2 plays a major role as a master regulator in ESCs. However, the underlying mechanisms by which Sox2 contributes to self-renewal or reprogramming processes remain to be determined. Here, we provide new evidence for a phosphorylation-based regulation of Sox2 activity. Akt directly interacts with Sox2 and promotes its stabilization through phosphorylation at Thr118, which enhances the transcriptional activity of Sox2 in ESCs. Moreover, phosphorylation of Sox2 cooperates in the reprogramming of mouse embryonic fibroblasts by enabling more efficient induction of iPSCs. Overall, our studies provide new insights into the regulatory mechanism of Sox2 in ESCs and also provide a direct link between phosphorylation events and somatic cell reprogramming.


Subject(s)
Cellular Reprogramming , Pluripotent Stem Cells/metabolism , SOXB1 Transcription Factors/metabolism , Amino Acid Sequence , Animals , Cell Differentiation/drug effects , Cell Line , Cell Proliferation/drug effects , Cellular Reprogramming/drug effects , Embryonic Stem Cells/cytology , Embryonic Stem Cells/drug effects , Embryonic Stem Cells/enzymology , Enzyme Activation/drug effects , Humans , Kruppel-Like Factor 4 , Leukemia Inhibitory Factor/pharmacology , Mice , Molecular Sequence Data , Phosphorylation/drug effects , Phosphothreonine/metabolism , Pluripotent Stem Cells/cytology , Pluripotent Stem Cells/drug effects , Protein Binding/drug effects , Protein Processing, Post-Translational/drug effects , Protein Stability/drug effects , Proto-Oncogene Proteins c-akt/metabolism , SOXB1 Transcription Factors/chemistry , SOXB1 Transcription Factors/genetics , Transcription, Genetic/drug effects , Ubiquitin/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...