Sox2 Research Articles

Criteria for predicting the development of recurrent peripheral nerve sheas tumors

Peripheral nerve sheaths tumors (PNST) account for about 8 % of all nervous system cancers. The relapse rate ranges from 17.3 to 26.4 %, showing an upward trend. The causes and provoking factors for the development of relapses of PNST have not been fully studied. Purpose of the study: to establish criteria for predicting recurrence of PNST. Material and Methods. The study included 122 patients who were treated at the Department of Spine and Peripheral Nerve Surgery of A.I. Polenov Russian Research Neurosurgical Institute from 2009 to 2021. Among them, there were 87 (71.3 %) patients with primary PNST and 35 (28.7 %) patients with recurrent PNST. All patients underwent MRI and ENMG both before and after surgery. An immunohistochemical study of Ki67 and SO X10 markers was performed. Results. The majority of relapses occured within 1 year after surgery. In cases with radical removal of PNST, the risk of relapse was: 28.6 % for schwannomas 28.6 %, 37.1 % for neurofibromas and 34.3 % for MP NST 34.3 % (p≥0.05). The risk of developing relapse of PNST was 2.9 times higher in patients aged ≥49 years than in patients aged ≤48 years (p<0.004). The larger the initial size of the tumor, the higher the risk of relapse in the late postoperative period. The risk of developing relapse of MP NST was 8.79 times higher in patients with tumor size of greater than 11.5 cm than in patients with smaller tumor size (p<0.02). The of Ki67 level above 4.85 % in schwannomas and above 5.17 % in neurofibromas can predict relapse of PNST (p<0.05). Loss of SO X10 protein expression was associated with an increase in histological anaplasia of the tumor, which causes a high risk of relapse and an unfavorable clinical course of the disease. Conclusion. Despite radical (total) resection of PNST, the risk of relapse remains high. The pathological type of tumor, its size, levels of SO X10 and Ki67 markers, patient’s age, degree of preoperative neurological deficit and extent of surgery are significant criteria for predicting the development of relapse of PNST.

TGF-β1/WISP1/Integrin-α interaction mediates human chondrocytes dedifferentiation.

To clarify the interaction between TGF-β1 and WISP1, and the effect of Integrin α5/V subunits on the WISP1 caused chondrocyte (CH) dedifferentiated phenotype. The knee joint cartilage from the trauma and osteoarthritis (OA) patients were collected. The patients of trauma group were confirmed to have no OA history. The protein level of WISP1, Integrin-α5/V, and type II/I collagen were analyzed by Western blotting. Besides, we isolated the CHs from the cartilage without OA and treated CHs with exogenic TGF-β1 and WISP1 protein. In addition to this, to regulate the α5 and αV subunits expression of CHs, we silenced two genes by siRNA transfection and upregulated them by exogenic protein supplement. Then, the CHs with different α5 and αV expression were treated with WISP1. To value the chondrogenic gene expression, we determined the type II collagen and SOX9 gene expression by immunofluorescence (IF) and RT-PCR, respectively. Meanwhile, the dedifferentiation markers of CH, type I collagen, and Runx2 expression was also analyzed. Cell proliferation was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. The OA cartilage contains a higher level of type I collagen, WISP1, Integrin α5, and Integrin αV, but low type II collagen. The upregulation of TGF-β1 caused the increase of WISP1, as well as the high level of Integrin α5/V, and dedifferentiated gene. Besides, the upregulation of WISP1 also contributed to the TGF-β1 expression and CHs dedifferentiation. Apart from this, the silencing of the α5 subunit of Integrin aggravated the WISP1 induced CHs dedifferentiation, which was reversed by α5 upregulation. However, the αV subunit played an opposite role that mediated the WISP1-induced CHs dedifferentiation. Additionally, the interaction between TGF-β1 and WISP1 promoted the CHs proliferation, which was not affected by the Integrin-α5/V expression. TGF-β1 and WISP1 interact to induce CHs dedifferentiation, which was mainly by the mediation of the Integrin-αV subunit. On the contrary, Integrin-α5 shows a protective effect during the WISP1 caused CHs dedifferentiation.

Timosaponin Inhibit Proliferation and Stem Cell Formation of Lung Cancer Through Regulating Hedgehog Signaling-mediated SOX2

Timosaponin Inhibit Proliferation and Stem Cell Formation of Lung Cancer Through Regulating Hedgehog Signaling-mediated SOX2

Low expression of CircRNA HIPK3 promotes osteoarthritis chondrocyte apoptosis by serving as a sponge of miR-124 to regulate SOX8.

CircRNA, a type of circular RNA, has recently been shown to be a potential target for osteoarthritis (OA). Circular RNA HIPK3 (CircHIPK3) is reported to be abnormally expressed in various disease tissues and affects the occurrence and development of the disease. However, the role and underlying mechanism of CircRNA HIPK3 in osteoarthritis are still unclear. The purpose of this study is to explore the effect of CircRNA HIPK3 on osteoarthritis and analyze its regulatory mechanism. We took human OA tissues, normal knee cartilage, human OA chondrocytes and normal chondrocytes as the research objects. Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was used to detect CircHIPK3 expression level, its target gene miRNA 124 (miR-124) and downstream target molecule SOX8. Flow cytometry analysis was applied to discover the apoptosis of CircHIPK3 and miR-124 on OA cartilage in different transfection situations. Moreover, Western blot and RT-qPCR were used to detect the expression of caspase-3 in OA chondrocytes. The binding site of CircRNA HIPK3 and miR-124, miR-124, and SOX8 were verified by using Dual-Luciferase assay. High expressed CircHIPK3 and low expressed miR-124 were found in OA tissues and OA chondrocytes. In addition, the Dual-Luciferase report showed CircHIPK3 acted as a sponge of miR-124 in OA chondrocytes. CircHIPK3 and miR-124 expression in OA tissue were confirmed to be negatively correlated. To our surprise, knocking down CircHIPK3 and transfected miR-124 mimics both inhibited the apoptosis of OA chondrocytes. Further experiments verified that the downstream target molecule of miR-124 was SOX8 in OA chondrocytes. Besides, miR-124 inhibitors reversed the knockdown of CircHIPK3 while si-SOX8 reversed the miR-124 inhibitors effect of apoptosis on OA chondrocytes. Our results demonstrated that CircHIPK3 was significantly upregulated in OA cartilage tissue and cells. Low expression of CircHIPK3 promoted the apoptosis of OA chondrocytes by promoting miR-124 to suppress SOX8 expression. The molecular mechanism of CircHIPK3 in present study is expected to provide new ideas for the treatment of osteoarthritis.

Long non-coding RNA SNHG7 promotes migration and invasion of melanoma via upregulating SOX4.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long non-coding RNA SNHG7 promotes migration and invasion of melanoma via upregulating SOX4, by C. Zhang, B. Zhu, X.-B. Li, Y.-Q. Cao, J.-C. Yang, X. Li, Y.-X. Liu, Y.-B. Wang, published in Eur Rev Med Pharmacol Sci 2019; 23 (11): 4828-4834-DOI: 10.26355/eurrev_201906_18069-PMID: 31210315" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18069.

Effects of Prostaglandin E2 Receptor 4 Agonist on the Expression of Stem Factors in Human CD34+ Cells

To investigate the effect of prostaglandin E2 recoptor 4 antagonist (EP4A) on the self-renewal ability of human CD34+ cells and its mechamism. The peripheral blood hematopoietic stem cell of 20 healthy donors received the G-CSF-mobilization were collected, then the human CD34+ cells were sorted out by MACS microbead kit. The human CD34+ cells were treated with DMSO (control group), EP4A (EP4A group) and EP4A+EP4A antagonist (EP4A+EP4A group) for 72 hours. The differential genes and pathways related with CD34+ cell stemness were detected by Thermogram and Pathway enrichment analysis. and then the expression levels of protein and gene (β-catenin, Nanog, Oct4, Sox2, Stat3, AKT, P38) were detected by qRT-PCR and Western blot respectively. EP4A could elevate the mRNA and protein expression of β-catenin, Nanog, Oct4, Sox2, in comparison with control group, however, mRNA and protein expression of STAT3, AKT, P38 were not changed. When human CD34+ cell were cultured with EP4A+XAV939 it was found that the mRNA and protein expression of β-catenin was downregulated, moreover the mRNA and protein expression of Nanog, Oct4, Sox2 were reduced. EP4A can upregulate stemness factors-β-catenin, Nanog, Oct4 and Sox2 in human CD34+ cell in vitro, but not STAT3, AKT and P38.

Expression of apoptosis and myogenesis related genes during prenatal life in two divergent breeds of pigs

We aimed to evaluate apoptosis and myogenesis related genes expression in embryos and fetuses from two divergent genetic groups of pigs: Piau breed and a commercial line. Thirty females (15 Piau and 15 commercial line) were selected at 120 days of age. Estrous cycle was observed and on the third estrus females were considered sexually mature. Gilts were inseminated with semen from males of the respective breed. Three females from each breed were slaughtered at five different gestational ages: 15, 30, 45, 60 and 90 days. Whole embryos (15 and 30 d) and samples of longissimus dorsi muscle from fetuses (45, 60 and 90 d) were collected for RNA extraction. Expression of apoptosis and myogenesis related genes (BAX, BCL2, FGF4, IHH, HHIP, SHH, SOX2, WNT1 and WNT4) were evaluated by quantitative real time PCR. There was significant effect of interaction between breeds and gestational ages for all genes evaluated (P < 0.05). The BCL2 gene expression differed throughout pregnancy in Piau group with lower expression on day 15. The IHH gene expression throughout pregnancy was lower on days 15 and 60 in Piau group and lower on day 90 in commercial line group; and the SHH gene expression throughout pregnancy was higher on day 30 and lower on day 60 in Piau group and lower on day 45 in commercial group. The WNT1 gene expression along pregnancy was lower on day 15 and higher on days 30 and 45 in Piau group, and it was higher on day 30 than days 15 and 60 in commercial group. WNT4 gene expression throughout pregnancy was lower on day 15 in Piau group, and it was lower on day 30 in commercial pigs. Piau group presented higher expression of the FGF4 gene on days 45, 60 and 90, and commercial group showed higher expression on day 15 and 90. SOX2 gene expression was lower on day 15 in Piau pigs and it was constant throughout pregnancy in commercial group. Overall, the expression of IHH, SHH, WNT1, WNT4 and FGF4 genes were higher in commercial than Piau pigs on day 15, besides expression of BCL2 gene in Piau embryos was lower on day 15; these results might indicate that the muscle precursor cells are allowed to proliferate for a longer time in commercial than in Piau embryos by the balance of proliferative and apoptotic genes. Therefore, the expression differential between breeds can stimulate proliferation and differentiation of cells in different ways, explaining the postnatal differences in the muscularity between pigs from Piau breed and a commercial line.

A case report of neurofibroma of the testis

Neurofibromas are benign tumors of the peripheral nerve sheath originated from mesenchymal tissue and can occur throughout the body, but rarely in the testis. The preferred imaging method is ultrasound. The contrast-enhanced ultrasound can assist in showing the lesions. The characteristic pathological changes are positive of S100 and SOX10 with immunohistochemical staining. It is recommended to choose organ-sparing surgery because of the good prognosis. Key words: Testicular neoplasms; Neurofibroma; Case reports

Upregulation of Neuroprogenitor and Neural Markers via Enforced miR-124 and Growth Factor Treatment.

Previous studies have shown that miR-124 plays an important role in the development of auditory neurons, which are degenerated in the sensorineural hearing loss. However, whether the combined use of miR-124 and growth factors can increase the expression of neural related markers in human dental pulp stem cells has been remained unknown so far. In this study, human dental pulp stem cells were transfected with miR-124 following treatment with brain-derived neurotrophic factor or epidermal growth factor/basic fibroblast growth factor. The expression of some neural related markers (nestin, SOX2, β-tubulin III, MAP2, and peripherin) was analyzed in two groups by qRT-PCR or immunofluorescence. Cellular treatment resulted in morphological changes including neurosphere-like colonies formation. Nestin and SOX2 were up-regulated, and MAP2 and peripherin were down-regulated in dental pulp stem cells transfected by miR-124 following treatment with brain-derived neurotrophic factor. Replacement of brain-derived neurotrophic factor with epidermal growth factor/ basic fibroblast growth factor resulted in the up-regulation of nestin, MAP2, peripherin, and β-tubulin III and down-regulation of SOX2. The expression of SOX2 and nestin was also confirmed by immunofluorescence. The combination of miR-124 and growth factors would provide a promising starting point for upregulating the neural progenitor markers in human dental pulp stem cells.

Long non-coding RNA PVT1 functions as an oncogene in ovarian cancer via upregulating SOX2.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long non-coding RNA PVT1 functions as an oncogene in ovarian cancer via upregulating SOX2, by M.-F. Zou, J. Ling, Q.-Y. Wu, C.-X. Zhang, published in Eur Rev Med Pharmacol Sci 2018; 22 (21): 7183-7188-DOI: 10.26355/eurrev_201811_16251-PMID: 30468460" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/16251.

Generation of sepsis encephalopathy patient-specific inducible pluripotent stem cells with urine cells

To recombine the induced pluripotent stem cells (iPSC) derived from the urine of septic encephalopathy (SE) patients, and provided a specificity cell model to explore the mechanism of the neuronal damage and treatment for SE patients. Urine of SE patient was collected, and tubular epithelial cells were isolated and cultured from the urine. iPSC were derived from SE patient by introducing 4 transcription factors OCT4, Klf4, Sox2, c-Myc (OKSM) into patient-specific urine cells by Millipore's Human STEMCCATM Constitutive Polycistronic (OKSM) Lentivirus Kit. Colony morphology, alkaline phosphatase (AKP) activity, immunofluorescence staining, quantitative reverse transcription-polymerase chain reaction (RT-qPCR), and differentiation ability were used to identify the pluripetency of these iPSC lines. In addition, neurons were derived from these iPSC by inhibiting transforming growth factor-β (TGF-β) pathway. The SE-iPSC exhibited morphological and growth characteristics of human embryonic stem cell (hES), showed positivity for AKP by histochemical staining, and expressed embryonic stem cell (ESC) marker genes. There was a significant statistical difference in ESC-marker mRNA expression between the SE-iPSC and the urine cells [NANOG mRNA (2-ΔΔCt): 1.153±0.142 vs. 0.126±0.024, t = -10.688; REX1 mRNA (2-ΔΔCt): 1.419±0.206 vs. 0.103±0.066, t = -14.245; OCT4 mRNA (2-ΔΔCt): 1.233±0.176 vs. 0.201±0.022, t = -9.028; Sox2 mRNA (2-ΔΔCt): 1.334±0.119 vs. 0.159±0.017, t = -12.653, all P < 0.01]. Subcutaneous injection of iPSC into NOD-SCID mice resulted in teratomas containing tissues from all the 3 germ layers. Furthermore, neurons were successfully induced from SE-iPSC. The SE patient-specific iPSC could be generated from urine cells and differentiated into neurons, furthermore, the SE-iPSC cell line can be used as models for further elucidating the cellular pathology and developing therapeutic strategies for SE.

The miRNA-206 mediated the differentiation of bone mesenchymal stem cells into chondrocytes and its effect in osteoarthritis models

Objective To investigate the differentiation of bone mesenchymal stem cells(BMSCs) into chondrocytes by miRNA-206 and its mechanism in osteoarthritis(OA). Methods From January, 2017 to July, 2018, rat BMSCs were isolated, and their CD90 and CD45 were detected by flow cytometry. Transfection of miRNA-206 or miRNA-206 inhibitors into BMSCs using lentiviral vectors, dexamethasone induction for 14 d, then use alician blue staining and type II collagen immunostaining to detect chondrogenic differentiation. MTT assay was used to detect the proliferation of mesenchymal stem cells. Western blot analysis was used to detect the Aggrecan, Col II, Sox9 and Runx2 markers in chondroblast cells. The expression level of the marker gene of Sox9 mRNA in chondroblasts were detected by RT-PCR. OA rat models were treated with lentiviral vectors transfected with miRNA-206 or miRNA-206 inhibitors, and Aggrecan, Col II, Sox9, Runx2 which were the markers of chondrogenesis were detected by Western blot. Results The purity of isolated BMSCs was (80.7±3.9)%. BMSCs transfected with miRNA-206 could promote cell proliferation and increase chondrogenic differentiation. Western blot results showed that the expression of Aggrecan, Col II and Sox9 was increased in the miRNA-206 transfection group, and the expression of Runx2 was down-regulate. Meanwhile, RT-PCR results showed that miRNA-206 can up-regulate the expression of the chondroblast marker gene Sox9 mRNA in BMSCs. Compared with the OA group, miRNA-206 could increase the expression of Aggrecan, Col II and Sox9 signaling proteins in cartilage tissue (P<0.05), and down-regulate the expression level of Runx2(P<0.05). Conclusion The miRNA-206 can positively regulate the differentiation of BMSCs into chondrocytes, increase the ability of cell proliferation, up-regulate the expression of Aggrecan, Col II and Sox9, and down-regulate Runx2. The miRNA-206 increase chondrogenic capacity in rat models of osteoarthritis. Key words: Bone mesenchymal stem cells; Osteoarthritis; Chondrogenic differentiation; miRNA-206; Rat

The advance of endogenous neural stem cell features for retinal Müller cell

Neural stem cell is a kind of stem cells that can differentiate into neural and glial cells. While Muller cells, the main endogenous neural stem cell in retina,have the features to reentry into the cell cycle and differentiate into neural cells after retinal damage. Although it is highly effective for retinal Muller cell differentiation spontaneously after retinal injury in vertebrates, this feature is rigorous restricted in mammals. Recently, some transcription factors,such as Ascl1, Sox2, Lin28, Atoh7, are sufficient to drive quiescent Muller cells back in proliferation to generate new retinal neurons. Moreover, combining Ascl1 expression with a histone deacetylase inhibitor can bypass the limitation and increase the generation of new neurons in the adult retina. These regenerated neurons integrate the existing neuronal network and are able to respond to light, indicating that they can likely be used to restore vision. While these results are extremely promising, the regenerative response is still limited, likely because the proliferative capacity of mammalian Muller cells is low compared to their zebrafish counterparts. It is indeed necessary to identify new factors increasing the efficiency of the regenerative response. Key words: Neural stem cell; Microglia; Review; Muller cells

The clinical application value of seven tumor-associated autoantibodies in the diagnosis of non-small cell lung cancer

Objective This study was designed to evaluate the clinical value of seven combinedtumor-associated autoantibodies (7-TAAB) in the diagnosis of non-small cell lung cancer (NSCLC). Methods This is a cross-sectional study. The 81 newly diagnosed patients with NSCLC were enrolled. 46 patients with benign pulmonary diseases (BLD) and 55 healthy subjects were selected as the BLD group and the healthy control (HC) group, respectively. ELISA was used to detect the concentration of seven TAABs of p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGE A1 and CAGE in the serum of the NSCLC and the other two groups. The levels of lung cancer tumor markers CEA, NSE, SCC and CYFRA21-1 in serum were also detected in all enrolled subjects. Kruskal-wallis test was used for comparison among the three groups, Mann-Whitney test was used to evaluate the differences between the two groups, and positivity rates were analyzed by using standard χ2 tests and Fisher exact tests. The receiver operating characteristic (ROC) analyses were performed to evaluate the diagnostic efficacy of 7-TAAB or combination of 7-TAAB and traditional tumor markers. Results The serological levels of six TAABs (p53, SOX2, GAGE7, GBU4-5, MAGE A1, and CAGE) in the NSCLC group were higher than that in the BLD group (p53: Z=-4.370, P=0.000; SOX2: Z=-4.412, P=0.000; GAGE7: Z=-4.250, P=0.001; GBU4-5: Z=-2.678, P=0.025; MAGE A1: Z=-4.504, P=0.002; CAGE: Z=-4.646, P=0.001) and the HC group (p53: Z=-3.543, P=0.000; SOX2: Z=-3.383, P=0.002; GAGE7: Z=-4.893, P=0.001; GBU4-5: Z=-3.381, P=0.025; MAGE A1: Z=-3.369, P=0.001; CAGE: Z=-2.981, P=0.002),respectively. The differences were statistically significant. The comparison of PGP9.5 in NSCLC group with that in the BLD group was statistically significant (Z=-2.871, P=0.044), with that in the HC group was no difference (Z=-2.280, P=0.05). None of the seven TAABs showed a significant difference between the BLD group and the HC group (p53: Z=-1.917, P=0.917; PGP9.5: Z=-1.228, P=0.966; SOX2: Z=-1.789, P=0.325; GAGE7: Z=-0.563, P=1.000; GBU4-5: Z=-0.315, P=0.985; MAGE A1: Z=-2.310, P=0.857; CAGE: Z=-2.822, P=0.703). According to the criteria of cut-off value, the detection value of individual TAAB was judged as negative or positive. The specificity of every single TAAB to NSCLC was ≥89%, but the sensitivity was ≤39.5%. Positive in any of the single TAAB was considered as a positive result of 7-TAAB, the positive rate of 7-TAAB in NSCLC subgroups with early stages (stageⅠand stageⅡ) was considered higher than that of traditional biomarkers (7-TAAB:52.94%, CEA: 23.53%, NSE: 8.82%, CYFRA21-1∶20.59%, SCC:14.71%), and 7-TAAB was more sensitive to NSCLC patients with poor prognosis, such as advanced stages (stageⅢand stageⅣ) and moderately-poorly differentiation. The AUC of 7-TAAB was 0.734, with a sensitivity of 66.67% and a specificity of 80.20%. In coordination with 7-TAAB, CEA, NSE, CYFRA21-1 and SCC, the AUC was 0.917, with a sensitivity of 87.70% and a specificity of 81.20%. Conclusions 7-TAAB, regarded as a panel of serological markers, is helpful in NSCLC diagnosis and shows broad application prospect. The detection rate of 7-TAAB in patients with early NSCLC is superior to that of traditional serum tumor markers, and the combination of 7-TAAB with CEA, NSE CYFRA21-1 and SCC could improve the diagnosis sensitivity of patients with NSCLC. Key words: Carcinoma, non-small-cell lung; Autoantibodies; Biomarkers, tumor; Early Diagnosis

Molecular mechanism of Wnt pathway in regulating osteogenic and chondrogenic differentiation of adipose stem cells

Objective To explore the mechanism of Wingless-type MMTV integration site family (Wnt) pathway and SRY-related high mobility group-box gene 9 (Sox9) and Bone morphogenetic protein 2 (BMP-2) feedback regulation in regulating chondrogenic and osteogenic differentiation of adipose-derived stem cells (ADSCs). Methods The cartilage and osteogenic differentiation of ADSCs were stimulated by Lithium Chloride (LiCl) and Dickkopf related protein 1 (DKK-1). The markers of cartilage and osteogenic differentiation Collagen2a, Aggrecan, Core binding factor alphal 1 (Runx2), wingless-type MMTV integration site family, member 5A (Wnt5a) and Wnt pathway key proteins Sox9, BMP-2, β-catenin, Glycogen synthase kinase-3β (GSK-3β) were detected in early, middle and late stages. The full-length gene sequences of Sox9 and BMP-2 were transfected into ADSCs by lentivirus, respectively, then the expression levels of various indexes were detected again while stably expressed. Apply SPSS 20.0 statistical software for analysis and explore molecular mechanisms. Results During the cartilage differentiation of ADSCs, the Wnt pathway promotes its rapid proliferation and induces chondrogenic differentiation in the early and middle stages. The expression of Collagen 2a and Aggrecan was not significantly increased in the early, while significantly increased in the middle and late stages (t=1.484, 0.792, 8.598, 8.788, 3.333, 8.285, P 0.05). The expression of Runx2 was significantly increased in the middle and late stages (t=13.452, 12.148, 16.535, P<0.05), while the expression of Wnt5a was decreased (t=-4.017, -19.901, -7.181, P<0.05); overexpression expressed feedback activation of Wnt The pathway up-regulated β-catenin (0.26±0.08 vs. 0.64±0.05, t=8.789, P<0.05) and down-regulated Wnt5a (1.35±0.23 vs. 0.51±0.26, t=-5.233, P<0.05). The expression of BMP-2 was up-regulated in both groups (0.26±0.03 vs. 0.64±0.05; 0.47±0.03 vs. 1.15±0.15; 0.63±0.11 vs. 1.31±0.098, t=16.340, 8.750, 29.721, P<0.01). Conclusion The Wnt pathway regulates the cartilage and osteogenic differentiation of ADSCs by regulating Sox9 and BMP-2, respectively, and its regulatory mechanisms are distinct at different stages of differentiation. Key words: Adpose-derived stem cells; Chondrogenic differentiation; Osteogenic differentiation; Wingless-type MMTV integration site family/β-catenin signaling pathway

Gene expression profile of Sox2 and Nestin both were regulated by histone deacetylase in C17.2 neural stem cells

Histone deacetylation is a key modulator involved in proliferation, apoptosis and mRNA transcription . However, the effects of histone deacetylation in C17.2 neural stem cells (NSCs) are still not fully understood. In this study, C17.2 NSCs were used to evaluate the effects of nicotinamide and trichostatin A (TSA) on the transcription of several important genes. Here, we confirmed that the mRNA expression of sox1, sox2, p53 and bax in E14.5 NSCs were significantly higher than in C17.2 NSCs. There was no difference between E14.5 and C17.2 NSCs in the transcription of nestin. The transcription levels of p53 and nestin were significantly higher in C17.2 NSCs than in cerebral cortex, hippocampus, cerebellar cortex and olfactory bulb. The expression levels of sox1, sox2 and bax were upregulated in olfactory bulb as compared to the other three brain tissues. To further assess the effects of histone deacetylation in C17.2 NSCs, we used two histone deacetylase (HDAC) inhibitors, nicotinamide and TSA, to explore the differential changes in the expression of genes. The results indicated that the mRNA transcription of sox2, p53, nestin and bax was generally downregulated after exposure to nicotinamide and TSA, but the difference was statistically significant only for sox2 and nestin. In addition, there was no transcription of sox1. Thus our studies demonstration that C17.2 NSCs have different mRNA expression profiles compared to E14.5 NSCs and adult mouse brain tissues. Furthermore, HDAC inhibitors nicotinamide and TSA regulate gene expression through different histone acetylation.

Genetic etiology of 46, XY complete gonadal dysgenesis

46, XY complete gonadal dysgenesis(46, XY CGD)is a rare congenital genetic disease.Individuals with 46, XY CGD are characterized by female external genitalia, Mullerian duct structures and streak gonads.The pathogenesis of this disease is complex, which is related to the variation of sex determination genes in humans.In addition to the classic genes SRY, SOX9 and NR5A1, it has been found that the disease can be caused by the signal pathways such as DHH and MAPK, as well as other regulatory factors such as ubiquitination in recent years.However, only less than 50% of patients receive an accurate clinical genetic diagnosis.Facilitated by ongoing developments in genetic sequencing technologies, more and more potential pathogenic genes have been discovered, enriching the gene regulatory network of sex determination.The proper and prompt diagnosis and treatment of 46, XY CGD are always challenging, given the low rate of diagnosis and the risk of gonadal malignancy, which are imperative for long-term management of the individuals.Recently, great progress has been made in the study of 46, XY CGD both at home and abroad. Key words: Disorders of sex development; Gonadal development; Gene; Signaling pathways

Proliferative capacity of neural stem cells in hippocampus of rats after traumatic brain injury and its relationship with Janus kinase 2/signaling and transcriptional activation factor 3 signaling pathway

Objective To investigate the proliferative capacity of neural stem cells (NSCs) in rat hippocampus after traumatic brain injury (TBI) and its relationship with Janus kinase 2/signaling and transcriptional activation factor 3 (JAK2/STAT3) signaling pathway activity. Methods A total of 108 SD rats were randomly divided into control group (36 rats) and TBI group (72 rats). The TBI model was constructed by PinPoint™ Precision Cortical Impactor. At 1, 3, 7, 14, 21 and 28 days after injury, the brain tissues were taken for immunofluorescence staining to detect the proliferation of NSCs [5-bromodeoxyuridine (BrdU)+ /stem cell key protein-2 (Sox2)+ ] in hippocampus, and phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) were detected by Western blot. The expression level of p-JAK2 and p-STAT3 as well as the changing trend were analyzed. On the basis of preliminary analysis of the proliferation of NSCs and the change of JAK2/STAT3 signaling pathway activity in hippocampus, another 24 SD rats were randomly divided into TBI+ normal saline group and TBI+ AG490 (JAK2 specific inhibitor) group, with 12 rats in each group. At 7 days after injury, the proliferation of NSCs in hippocampus was detected by immunofluorescence staining, and the expression levels of p-JAK2 and p-STAT3 were detected by Western blot, so as to further confirm the correlation between the proliferation ability of NSCs in hippocampus and JAK2/STAT3 signaling pathway. Results Compared with the control group, the number of NSCs in the hippocampus of the TBI group and the expression of p-JAK2 and p-STAT3 increased. And the most significant increase occurred at 7 days after injury [number of NSCs: 31.2±4.7 in the control group, 111.4±8.1 in the TBI group (P<0.01); p-JAK2: 1.11±0.09 in the control group, 2.16±1.01 in the TBI group (P <0.01); p-STAT3: 1.05±0.06 in the control group and 2.06±0.09 in the TBI group (P<0.01)]. The proliferation of NSCs in hippocampus of TBI group was consistent with the change of p-JAK2 and p-STAT3 expression. Seven days after injury, the expression levels of p-JAK2 and p-STAT3 and the proliferation ability of NSCs in the TBI+ AG490 were significantly decreased [p-JAK2: 2.18 ± 0.15 in the TBI + isotonic saline group, 1.24±0.10 in the TBI+ AG490 group (P<0.01); p-STAT3: 2.21±0.12 in the TBI+ isotonic saline group, 1.25±0.11 in the TBI+ AG490 group (P<0.01); NSCs number: 112.8±8.6 in the TBI+ isotonic saline group, 75.5±6.4 in the TBI+ AG490 group (P<0.05)]. Conclusions The proliferation of NSCs in hippocampus of rats increased after TBI, and the activity of JAK2/STAT3 signaling pathway also increased, following the same trend. JAK2 inhibitor AG490 can reduce the activity of JAK2/STAT3 signaling pathway and the proliferation of NSCs. This can provide reference for researches on TBI promoting nerve regeneration and function repair. Key words: Brain injuries; Neural stem cells; Hippocampus; Signal transduction

LncRNA NR2F1-AS1 is involved in the progression of endometrial cancer by sponging miR-363 to target SOX4.

This study intended to investigate the role of lncRNA NR2F1-AS1 in endometrial cancer (EC). The expression level of NR2F1-AS1 in tumor tissues and EC cells was measured. After sh-NR2F1-AS1 transfection, the cell viability, apoptosis, migration and invasion of EC cells were analyzed. Luciferase reporter assay was conducted to investigate the target gene of miR-363. The expression levels of PI3K/AKT/GSK-3β pathway-associated factors were assayed using western blot. NR2F1-AS1 was significantly overexpressed in EC tissues and cells. NR2F1-AS1 inhibition decreased EC cell viability, migration and invasion, while promoted cell apoptosis. miR-363 was negatively regulated by NR2F1-AS1. SOX4 was a target of miR-363. NR2F1-AS1 functioned on EC progression via PI3K/AKT/GSK-3β pathway. The results demonstrated that NR2F1-AS1 was highly expressed in EC, which involved in the proliferation and migration of EC cells through downregulation of miR-363 to target SOX4 and regulating PI3K/AKT/GSK-3β pathway.

Expression of SOX11 and HER2 and their association with recurrent breast cancer

Background: Recurrent breast cancer occurs as a result of divergent gene expression in response to therapeutic intervention. A recent report showed that SOX11 , an embryogenic mammary transcription factor, is overexpressed in breast cancer. HER2 is also dysregulated in breast cancer stem cells; however, the relative expression of these two genes in recurrent breast cancer has not been investigated. Methods: Mouse models of mild and advanced stage recurrent breast cancer were developed via implantation of different doses of 4T1 Luc2GFP cells. The cellular morphology of normal and recurrent breast cancer tissues was analyzed using standard histological methods. SOX11, HER2 , and ALDH1 expression levels were analyzed via immunohistochemistry and western blotting. Results: Histological analyses revealed that treatment with doxorubicin limited mild recurrent cancer but was ineffective against advanced stage recurrent cancers, as evidenced by increased cell proliferation. SOX11 was consistently overexpressed in mild and advanced stage breast cancers treated with doxorubicin, relative to HER2 , which exhibited reduced expression in response to doxorubicin treatment in both mild and advanced stage recurrent breast cancer. In advanced stage recurrent breast cancer, SOX11 expression was more readily observed across the cell surface and was correlated with the overexpression of the breast cancer stem cell marker ALDH1 . Conclusions: These results show that SOX11 expression was directly associated with breast cancer stem cell populations. In contrast, HER2 expression was strongly associated with drug treatment effects, but was not correlated with breast cancer stem cell survival in recurrent breast cancer.