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Objective:To observe any effect of exosomes derived from umbilical cord mesenchymal stem cells on pain, cartilage repair and the expression of transcriptional activator 3 (ATF-3) and growth related protein 43 (GAP-43) in the dorsal root ganglia (DRG), as well as to explore the mechanism of their relieving pain.Methods:Fifty-four male Sprague-Dawley rats were randomly divided into a sham-operation group, a monoiodoacetate group and an exosome group, each of 18. The knee cavities of the left hind limbs of all of the rats except those in the sham-operation group were injected with 50μl of monoiodoacetate to establish an arthritis pain model. The sham-operation group received only 50μl of saline solution as controls. Two weeks after the modelling, the knee joint cavities of the exosome group were injected with 50μl of exosomes, while the other two groups were injected with 50μl of normal saline. The rats′ mechanical and thermal pain thresholds were measured 1 day before the modeling, 7 and 14 days after the monoiodoacetate injection, as well as 7, 14 and 28 days after the exosome injection. Western blotting was used to detect the expression of ATF-3 and GAP-43 in the rats′ DRG, while hematoxylin and eosin staining was used to detect any cartilage repair.Results:Compared with the monoiodoacetate group, the latency of the mechanical and thermal pain thresholds had increased significantly in the exosome group 7 days after the exosome injection. The difference remained significant until the 28th day after the injection. The expression of ATF-3 protein decreased significantly and that of the GAP-43 protein increased significantly. Significant differences were observed in the average Osteoarthritis Research Society International (OARSI) knee cartilage score.Conclusions:Exosomes can alleviate the pain induced by monoiodoacetate adjuvant. The analgesic mechanism may be related to reducing nerve injury and promoting nerve and cartilage repair, with the nerve repair earlier than cartilage repair.
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Objective@#As solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) share the same molecular genetics features, the 2016 WHO classification of central nervous system (CNS) tumors had created the combined term SFT/HPC and assigns three grades. This study aims to investigate the clinicopathologic characteristics, diagnosis, differential diagnosis and prognosis of CNS SFT/HPC.@*Methods@#Seventy-one cases of CNS SFT and HPC were retrospectively reclassified and studied. Histopathological, immunohistochemical and imaging features were analyzed. The follow-up data were analyzed.@*Results@#There were 37 male and 34 female patients. The median age was 48 years (range, 3-77 years). Twelve cases (17%) were WHO grade Ⅰ, 26 (37%) were WHO grade Ⅱ and 33 (46%) were WHO grade Ⅲ. Microscopically the tumor could show traditional SFT phenotype, HPC phenotype or mixed phenotype. Immunochemically, 97%(69/71) were positive for STAT6, with 96%(66/69)showing diffuse strong staining. Approximately 90% were diffusely positive for bcl-2, CD99 and vimentin. The expression rate of CD34 decreased with increasing tumor grade, and the mean expression rate was 78%. SSTR2a was variably expressed in 10% (7/71) of cases including one case showing strong cytoplasmic staining. A few cases expressed EMA, CD57 and S-100 focally. The Ki-67 index ranged from 1% to 50%. Thirty four patients were followed up for 8-130 months; 12 patients(35%)had recurrences, and two (6%) had liver metastases.@*Conclusions@#CNS SFT/HPC is relatively uncommon. There was significant morphological overlap or transition between different grades. STAT6 is a specific marker for the diagnosis of this tumor. Surgical resection is the preferred treatment. WHO grade Ⅱ and Ⅲ SFT/HPC show rates of local recurrence and systemic metastasis, with liver being the most common site of extracranial metastasis.
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Objective To observe the effect of ATF6 on the apoptosis and proliferation of podocytes induced by palmitic acid (PA). Methods Podocytes were stimulated with different doses of PA for 24 h. The expression of cleaved-caspase3 was detected by Western blotting. The podocyte apoptosis was analyzed by flow cytometry (FCM), and the expression of ATF6 was tested by Western blotting and immunofluorescence staining. After the transfection of adenovirus siRNA against ATF6, the proliferation, the cell cycle and apoptosis of potocytes stimulated with PA were tested by MTT or FCM. Results The levels of cleaved - caspase3 and ATF6 of podocytes stimulated with PA were significantly increased by a dose-dependent manner compared with the control group (P<0.05). The apoptosis of podocytes stimulated with PA was increased (P<0.05). Compared with the podocytes stimulated with PA, the apoptosis of podocytes transfected by adenovirus siRNA against ATF6 with PA stimulation was significantly reduced (P<0.05). The proliferation of podocytes transfected by adenovirus siRNA against ATF6 and stimulated with PA, however, was obviously increased compared with the podocytes stimulated with PA (P<0.05). Conclusion ATF6 mediated the apoptosis of podocytes induced by palmitate acid.
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The research on tumor metabolism has become a new hotspot in recent years, of which the key regulatory molecules that mediating tumor metabolism are a priority for all. The transcriptional co-activator peroxisome proliferator-activated receptor gamma co-activator 1alpha (PGC-1α) is one of these key regulatory molecules. PGC-1α has been demonstrated to be a crucial regulatory molecule involved in a variety of metabolic diseases. It is also a key molecule in regulation of tumor metabolism, mediating oxidative metabolism and anabolism to participate in regulation of survival, proliferation and migration of tumor cells. This paper reviews the advances in research on structure of PGC-1α and its related transcription molecules, and explores the mechanism of PGC-1α in regulation of occurrence and development of tumors, especially focuses on advances in the role of PGC-1α in tumor metabolism, which may provide theoretical references for fundamental studies on antitumor metabolism based on PGC-1α target as well as the related drug development.
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Objective To investigate the expression and activation of extracellular signal-regulated kinase 1/2 (ERK 1/2), its upstream molecule, epidermal growth factor receptor (EGFR), and downstream transcription factor, Ets-like protein 1 (ELK-1), in lesions of psoriasis vulgaris, and to evaluate the relationship between ERK pathway and psoriasis vulgaris. Methods Tissue samples were obtained from the lesions of 40 patients with psoriasis vulgaris and normal skin of 20 normal human controls. Immunohistochemistry and Western blot were performed to detect the expressions of phosphorylated ERK1/2, EGFR and ELK-1 in the tissue samples.Results As immunohistochemistry showed, the integrated optical density (IOD) of p-ERK1/2, p-EGFR and p-ELK-1 was 269.85 ± 57.96, 136.88 ± 30.33 and 237.61 ± 56.29 respectively in the psoriatic lesions, significantly higher than that in the normal controls ( 140.24 ± 24.42, 110.66 ± 28.99 and 119.04 ± 21.99, respectively, all P ＜ 0.05). A positive correlation was observed between the expression of p-EGFR and p-ERK1/2(r = 0.57, P ＜ 0.05) and between that of p-ERK1/2 and p-ELK-1 (r=0.72,P＜0.05) in psoriatic lesions.Conclusion The enhanced signal transduction through phosphorylated EGFR→ERK1/2→ELK-1 pathway may play a certain role in the pathophysiological process of psoriasis vulgaris.
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Objective: To study the effect of HBx on the gene expression profile in the hepatocellular carcinoma cell line Huh7 and to provide the molecular evidence for exploring the role of HBx in the tumorigenesis of hepatoma. Methods: HBx gene was transfected into Huh7 cells carried by pcDNA3. 1b plasmid which contained the entire open reading frame (ORF) of HBx gene. The empty vector of pcDNA3. 1b was used as a control. The HBx expression in transfected cells was confirmed by Western blotting as compared with those transfected with empty vectors. And then a microarray analysis was performed to detect the gene expression profile in Huh-7 cells by Human Genome U133 Plus 2.0 Array of Affymetrix-GeneChip. Six differentiated expressed genes (3 up-regulated and 3 down-regulated) were selected randomly and verified with RFQ-PCR. Results: The microarray analysis revealed that 88 genes were significantly up-regulated and 111 genes were down-regulated in Huh7 cells after transfection with HBx gene as compared with those transfected with empty vector. The functions of these differentiated genes were related with many aspects. Conclusion: HBx affected hepatocellular carcinoma cell HuH-7 bi-directionally. It not only had transcription-activating effects but also had transcription-suppressing effects. These data had important value for understanding the role of HBx in tumorigenesis and development of hepatoma.