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Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.
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Objective To investigate the regulation of emodin on microRNA expressions in mouse model with sepsis by GeneChip microRNA array.Methods Forty two c57 mice were randomly (random number) divided into 3 groups:sham operation group (sham group,n=14),sepsis group(n=14) and emodin group (n=14).The sepsis model of the mouse was subjected to cecal ligation and puncture (CLP).Mice in emodin group received intraperitoneal injection of emodin (40 mg/kg) half an hour before operation and every 12 hours after CLP.All mice were sacrificed 48 h after surgery and part of the ileum were removed for intestine tissue stained with hematoxylin eosin.The levels of tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6) and intestinal fatty acid binding protein (I-FABP) in peripheral blood were measured by enzyme-linked immunosorbent assay (ELISA).Total RNA of ileum tissues was extracted from the sepsis group and emodin group,and thensubjected to miRNA microarray.The results of microarray were further verified by quantitative real-time PCR (qRT-PCR).Target genes of differentially expressed miRNAs were predicted and subjected to gene ontology (GO) and KEGG pathway enrichment analysis.Data of multi-groups were analyzed by one way variance (ANOVA) and inter-group comparisons were made by SNK-q tests.Mann-Whitney U test was used when homogeneity of variance were not met.The value of P＜0.05 was considered statistically significant.Results Compared to the sepsis group,the levels of serum TNF-α,IL-6 and I-FABP in the emodin group were decreased significantly.MiRNA microarray showed that 23 miRNAs were differentially expressed in the emodin group as compared to the sepsis group,among which 17 miRNAs were up-regulated and 6 miRNAs were down-regulated.qRT-PCR results were consistent with miRNA array data.Target genes of 10 selected miRNAs were predicted and subjected to bioinformatic analysis.A total of 3 410 target genes were significantly enriched in 2 072 GO biological process terms,246 GO cellular component items and 277 GO molecular function terms.Moreover,KEGG pathway analysis showed that these differential miRNAs were involved in the regulation of PI3K-Akt signaling pathway,MAPK signaling pathway,and TNF signaling pathway.Conclusions Emodin can regulate the expression of multiple microRNAs,and play an important role in protecting the intestinal mucosal barrier via a variety of targets and pathways.
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Objective@#To investigate the regulation of emodin on microRNA expressions in mouse model with sepsis by GeneChip microRNA array.@*Methods@#Forty two c57 mice were randomly (random number) divided into 3 groups: sham operation group (sham group, n=14),sepsis group(n=14) and emodin group (n=14). The sepsis model of the mouse was subjected to cecal ligation and puncture (CLP). Mice in emodin group received intraperitoneal injection of emodin (40 mg/kg) half an hour before operation and every 12 hours after CLP. All mice were sacrificed 48 h after surgery and part of the ileum were removed for intestine tissue stained with hematoxylin eosin. The levels of tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6) and intestinal fatty acid binding protein (I-FABP) in peripheral blood were measured by enzyme-linked immunosorbent assay (ELISA). Total RNA of ileum tissues was extracted from the sepsis group and emodin group, and then subjected to miRNA microarray. The results of microarray were further verified by quantitative real-time PCR (qRT-PCR). Target genes of differentially expressed miRNAs were predicted and subjected to gene ontology (GO) and KEGG pathway enrichment analysis. Data of multi-groups were analyzed by one way variance (ANOVA) and inter-group comparisons were made by SNK-q tests. Mann-Whitney U test was used when homogeneity of variance were not met. The value of P<0.05 was considered statistically significant.@*Results@#Compared to the sepsis group, the levels of serum TNF-α, IL-6 and I-FABP in the emodin group were decreased significantly. MiRNA microarray showed that 23 miRNAs were differentially expressed in the emodin group as compared to the sepsis group, among which 17 miRNAs were up-regulated and 6 miRNAs were down-regulated. qRT-PCR results were consistent with miRNA array data. Target genes of 10 selected miRNAs were predicted and subjected to bioinformatic analysis. A total of 3 410 target genes were significantly enriched in 2 072 GO biological process terms, 246 GO cellular component items and 277 GO molecular function terms. Moreover, KEGG pathway analysis showed that these differential miRNAs were involved in the regulation of PI3K-Akt signaling pathway, MAPK signaling pathway, and TNF signaling pathway.@*Conclusions@#Emodin can regulate the expression of multiple microRNAs, and play an important role in protecting the intestinal mucosal barrier via a variety of targets and pathways.
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Objective@#To investigate the clinical and histological features, diagnosis and differential diagnosis of myofibroma/myofibromatosis.@*Methods@#The clinical data and pathology features of nine cases of myofibroma/myofibromatosis were collected from August 2011 to November 2016 in Affiliated Drum Tower Hospital, Nanjing University Medical School and Children′s Hospital of Nanjing Medical University. Immunohistochemistry(IHC), PDGFRB molecular analysis and ETV6-NTRK3 gene fusion were performed and relevant literature reviewed.@*Results@#There were 7 males and 2 females, with age ranging from 3 days to 18 years (mean 5 years). The tumors were located in head and neck (eight cases) and trunk (one case). Clinically, the tumors presented as freely movable nodules. Microscopically, they appeared biphasic with alternating light- and dark-staining areas. The light-staining area consisted mainly of plump myoid spindle cells with eosinophilic cytoplasm arranged in nodules, short fascicles, or whorls.The dark-staining area was composed of round or polygonal cells with slightly hyperchromatic nuclei or small spindle cells arranged around a distinct hemangiopericytoma-like vascular pattern. IHC showed the tumor cells in the light-staining area were strongly positive for vimentin and SMA, while cells in dark-staining area were strongly positive for vimentin, and weakly for SMA. Tumor cells were negative for desmin, S-100 protein, h-Caldesmon, CD34 and STAT6. Analysis of PDGFRB mutations was performed in seven cases. Two cases showed 12 exon point mutation c. 1681 c>T(p.R561C), one case showed 14 exon point mutation c. 1998C>G (p.N666K). ETV6-NTRK3 gene fusion was not detected by fluorescence in situ hybridization in four patients under three years old. All cases were followed for 6 to 68 months, with two recurrences.@*Conclusions@#Myofibroma/myofibromatosis is an uncommon benign myofibroblastic tumor of infancy and childhood. The tumor can appear biphasic, and may show PDGFRB point mutation which is of potential diagnostic value.
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Objective@#To investigate the optimal strategy for immunohistochemical (IHC) staining in bone metastasis specimens from breast cancer.@*Methods@#Twenty-eight bone metastases specimens from breast cancers were divided into three groups and subjected to different decalcifying agents (group A-10% nitrate, group B-EDTA decalcification, and group C-imported decalcifying solution RapidCal). The effects of those on HE and IHC staining for Ki-67, ER, PR, GATA3, RANK, RANKL, HER2 and HER2 FISH results were assessed.@*Results@#There were no significant differences among three groups in HE morphology and IHC staining. Antigen content in the RapidCal group were all intact; the EDTA group showed a similar staining rate, which was better than the nitrate group (P<0.05). Nitrate group showed marked reduction in nuclear Ki-67 staining, but the loss of cytoplasmic antigens (RANK, RANKL) was less than cell membrane antigen (HER2). For FISH, the RapidCal group and EDTA group showed same results, concordant with IHC staining results. The expression of HER2 protein in the nitric acid group was significantly decreased and chromosome 17 labelling was lost (P<0.05).@*Conclusions@#RapidCal treated bone metastases specimens from breast cancer show excellent sample quality in morphological, IHC and FISH results compared with traditional decalcifying agents. Owing to the longer time of EDTA decalcification, the new decalcifying agent RapidCal plays an important role in quality control and clinical application.
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Familial hypercholesterolemia (FH) is an autosomal dominant disorder of lipid metabolism. Because the early FH can cause atherosclerosis, the morbid and mortality of severe cardiovascular disease are increased in patients. Thus more and more emphasis has been put on treatment with statin since childhood so as to improve the long-term prognosis. This article reviews the necessity, effectiveness and safety of statins in the treatment of FH in children, and also presents some existing problems and thoughts.
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Objective To investigate the effect of Danggui buxue decoction on ventricular remodeling and miR-34a expression after myocardial infarction in mice. Methods Mice myocardial infarction model were estab-lished by the left anterior descending coronary artery embolization. Then the mice were divided into Danggui buxue Decoction group and model group. Mice in Danggui buxue decoction group were given Danggui buxue decoction , and mice in the model group were given the equal volume of saline for 8 weeks. Cardiomyocyte apoptosis was detect-ed by TUNEL staining. Myocardial fibrosis was detected by Masson staining. The expression of miR-34a was detect-ed by quantitative PCR and the expression of Sirt1 was detected by Western blot assay. Results Compared with the model group ,the EF value of the mice was significantly improved (P < 0.05),the myocardial cell index decreased(P<0.05),the content of collagen fibers decreased(P<0.05),the expression of miR-34a decreased, but the expression of Sirt1 increased(P<0.05)in Danggui buxue Decoction group. Conclusion Danggui buxue decoction can effectively inhibit ventricular remodeling of mice following myocardial infarction ,which is associated with the suppression of miR-34a and the increase of Sirt1.
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Objective To explore the diagnosis and treatment of disseminated cryptococcosis involving the biliary tract and the central nervous system. Methods The clinical data of one child with disseminated cryptococcosis involving biliary tract and central nervous system were analyzed retrospectively. The related literatures were reviewed. Results A 6-year-old boy presented with jaundice, hepatic dysfunction and convulsions. The surgical treatment was performed. The pathological biopsy showed cryptococcal infection, cryptococcal capsular polysaccharide antigen latex agglutination test in serum and cerebrospinal fluid were positive and cerebrospinal fluid ink staining was also positive. After antifungal treatment, the symptoms were relieved and no sequelae existed during the follow-up period. Conclusion Disseminated cryptococcosis simultaneously involving the biliary tract and the central nervous system is rare in children.
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Objective To investigate the effect of Danggui buxue decoction on ventricular remodeling and miR-34a expression after myocardial infarction in mice. Methods Mice myocardial infarction model were estab-lished by the left anterior descending coronary artery embolization. Then the mice were divided into Danggui buxue Decoction group and model group. Mice in Danggui buxue decoction group were given Danggui buxue decoction , and mice in the model group were given the equal volume of saline for 8 weeks. Cardiomyocyte apoptosis was detect-ed by TUNEL staining. Myocardial fibrosis was detected by Masson staining. The expression of miR-34a was detect-ed by quantitative PCR and the expression of Sirt1 was detected by Western blot assay. Results Compared with the model group ,the EF value of the mice was significantly improved (P < 0.05),the myocardial cell index decreased(P<0.05),the content of collagen fibers decreased(P<0.05),the expression of miR-34a decreased, but the expression of Sirt1 increased(P<0.05)in Danggui buxue Decoction group. Conclusion Danggui buxue decoction can effectively inhibit ventricular remodeling of mice following myocardial infarction ,which is associated with the suppression of miR-34a and the increase of Sirt1.
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Objective To explore the diagnosis and treatment of disseminated cryptococcosis involving the biliary tract and the central nervous system. Methods The clinical data of one child with disseminated cryptococcosis involving biliary tract and central nervous system were analyzed retrospectively. The related literatures were reviewed. Results A 6-year-old boy presented with jaundice, hepatic dysfunction and convulsions. The surgical treatment was performed. The pathological biopsy showed cryptococcal infection, cryptococcal capsular polysaccharide antigen latex agglutination test in serum and cerebrospinal fluid were positive and cerebrospinal fluid ink staining was also positive. After antifungal treatment, the symptoms were relieved and no sequelae existed during the follow-up period. Conclusion Disseminated cryptococcosis simultaneously involving the biliary tract and the central nervous system is rare in children.
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Lung adenocarcinoma is usually thought to follow a linear multistep progression schema,that is precancerous lesions progress to adenocarcinoma in situ,and progress to micro-invasive adenocarcinoma,eventually some lung adenocarcinoma happen diffusion.However,recent findings reveal that this linear progression schema might not occur in all lung adenocarcinoma subtypes,and some subtypes show a kind of non-linear progression schema.The study of these two kinds of schemas can help for early detection of lung adenocarcinoma.