Objective To investigate children′s myelodysplastic hematopoietic cells reaction to interleukin (IL)-15.Methods CD 34 + cells in bone marrow from 18 myelodysplast syndrome(MDS) patients were purified by an immunomagnetic beads sorting system. Apoptosis of hematopoietic precursors was assayed by propidium iodine staining and flow cytometric analysis.Results On 8th cultured day,when IL-15 concentration was between 0-100 ng/ml,it could suppress apoptosis of hematopoietic cells in MDS patients in a dose-and- time dependent manner. IL-15 in study group significanthy lower than that of control group.Conclusion IL-15 may partly suppress apoptosis of hematopoietic cells in MDS patients.

To study the effect of interleukin-15 (IL-15) on the proliferation, differentiation and apoptosis of MDS CD34(+) cells, CD34(+) cells of high enrichment were separated by MACS system, and cultured in liquid media with different concentration of IL-15 in treated group and without IL-15 in the control group. Apoptosis of hematopoietic precursors was assayed by propidium iodine staining and cell by FCM, and the other MDS CD34(+) cells were stained by cytochemical staining after culture. The results showed that after culture with IL-15 the proliferation and differentiation of MDS CD34(+) cells were obviously promoted. It was found the every lineage of mature cells developed, the expressions of cell surface antigens CD71, CD33 and CD19 all increased in the MDS CD34(+) cell treated with IL-15. It is suggested that IL-15 stimulates the proliferation and differentiation of MDS CD34(+) cells, and partly shows anti-apoptosis effects which may be applicable to the therapy MDS.
Antigens, CD ; immunology ; Antigens, CD19 ; immunology ; Antigens, CD34 ; immunology ; Antigens, Differentiation, Myelomonocytic ; immunology ; Apoptosis ; drug effects ; Bone Marrow Cells ; drug effects ; immunology ; pathology ; Cell Cycle ; drug effects ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Flow Cytometry ; Humans ; Interleukin-15 ; pharmacology ; Microscopy, Fluorescence ; Myelodysplastic Syndromes ; blood ; immunology ; pathology ; Receptors, Transferrin ; immunology ; Sialic Acid Binding Ig-like Lectin 3

BACKGROUNDIntegrin-linked kinase (ILK) dysregulation is involved in the progression of diabetic nephropathy (DN). The aim of this study was to investigate the effects of angiotensin II receptor blocker (ARB), irbesartan, on ILK expression and podocyte injury in DN.

METHODSDN was induced by the combined feeding of high-sucrose, high-fat diet and intra-peritoneal injection of low dose of streptozotocin (35 mg/kg) in spontaneously hypertensive rats. Diabetic rats were treated with irbesartan (50 mg×kg(-1)×d(-1)) by gavage for 8 weeks. The renal morphologic changes and podocyte injury were investigated by light and electron microscopy, and the ILK expression was evaluated by real-time RT-PCR and Western blotting analysis.

RESULTSDiabetic rats exhibited with the similar clinical feature of type 2 DN. Morphologically, they were characterized by expansion of mesangial matrix, loss of podocyte and podocyte injury. Impressively, compared to controls, the ILK expression in diabetic rats were upregulated, which were positively correlated with both podocyte injury and albuminuria. Irbesartan significantly prevented ILK overexpression, along with the amelioration of podocyte injury and albuminuria.

CONCLUSIONSILK plays an important role in mediating podocyte injury in DN; irbesartan inhibits ILK upregulation and attenuates podocyte injury, which might offer a new insight into the role of ARB in preventing DN progression.

Angiotensin Receptor Antagonists ; therapeutic use ; Animals ; Biphenyl Compounds ; therapeutic use ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; Enzyme Activation ; drug effects ; Male ; Podocytes ; drug effects ; Protein-Serine-Threonine Kinases ; metabolism ; Rats ; Rats, Inbred SHR ; Tetrazoles ; therapeutic use

BACKGROUNDMutations in PAX6 gene have been shown to be the genetic cause of aniridia, which is a severe panocular eye disease characterised by iris hypoplasia. However, there is no study to do genetic analysis of aniridia, although there are several case reports in China. Here, we describe a mutation analysis of PAX6 in a large Chinese family with aniridia.

METHODSGenomic DNA from venous blood samples was prepared. Haplotype analysis was performed with two genetic markers (D11S904 and D11S935). Fourteen exons of the PAX6 gene were amplified from genomic DNA. Polymerase chain reaction (PCR) products of each exon were analysed by single strand conformational polymorphism (SSCP). The PCR products having an abnormal pattern were sequenced to confirm the mutation.

RESULTSSignificant evidence for allele sharing in affected patients was detected suggesting that PAX6 mutation links to aniridia in this family. An extra band corresponding to exon 9 in PAX6 was found by single strand conformational polymorphism analysis in all the aniridia patients in this family, but not detected in the unaffected members. A mutation of C to T was detected by sequencing at the nucleotide 1080 that converts the Arg codon (CGA) to the termination codon (TGA).

CONCLUSIONSAniridia is caused by a nonsense mutation of PAX6 gene in the large Chinese kindred. Genetic test is important to prevent the transmission of aniridia to their offsprings in the kindred by prenatal diagnosis.

Aniridia ; genetics ; Eye Proteins ; genetics ; Female ; Homeodomain Proteins ; genetics ; Humans ; Male ; Mutation ; PAX6 Transcription Factor ; Paired Box Transcription Factors ; Pedigree ; Repressor Proteins ; genetics

Abstract：Objective To predict the structure and function of sterol O⁃acyltransferase 1（SOAT1）related to hepatocellular carcinoma（HCC）by using bioinformatics tools，in order to understand its mechanism as the marker and therapeutic target of S⁃Ⅲ subtype. Methods The structure，function and protein interaction of SOAT1 were predicted and analyzed by using databases or softwares such as NCBI，STRING，Protscale，SignalP，TMHMM，PSORT，SOPMA，SWISS ⁃ MODEL， NetNGlyc，NetOGlyc，Netphos and ProtParam. Results The protein encoded by SOAT1 was a hydrophobic protein with good stability，which was a nonclassical pathway protein with 8 transmembrane regions，mainly distributed among the cell membrane. SOAT1 was expressed in many tissues，while most of them in the adrenal gland，which showed multiple phosphorylation sites and was mainly involved in the synthesis and catabolism of cholesterol. Conclusion Bioinformatics analysis of structure and function of SOAT1 showed that SOAT1 lipid synthesis and catabolism pathways played an important role，and lipid expression was closely related to the development of cancer，indicating that the treatment of HCC may be achieved by regulating the expression of SOAT1 gene.

Objective: To investigate clinical significance of microRNA-130b (miR-130b) in osteosarcoma and its role in cell growth and invasion. Methods: miR-130b expression was detected in 68 samples of surgically resected osteosarcoma and matched normal tumor-adjacent tissues by qRT-PCR. The expression of miR-130b was altered by corresponding vectors in osteosarcoma cells, and then Western blot was used to detect the expression of PPARγ. BrdU cell proliferation and Transwell assays were performed to determine cell proliferation and invasion. Results: The expression of miR-130b in osteosarcoma tissues was significantly higher than that in normal tumor-adjacent tissues. Its expression in patients with metastasis was significantly higher than that in those without metastases. miR-130b expression in tumor tissues was significantly associated with tumor size, clinical stage and distant metastasis. And its expression was significantly correlated with overall survival and disease free survival. miR-130b overexpression obviously repressed the expression of PPARγ, and resulted in significant increase of Saos-2 cell proliferation and invasion. On the contrast, repressing miR-130b expression with its inhibitor significantly increased PPARγ expression, and inhibited MG-63 cell proliferation and invasion. Conclusions: The high-expression of miR-130b is correlated with the adverse clinicopathological features and poor prognosis in osteosarcoma. miR-130b may regulate proliferation and invasion of osteosarcoma cells by targeting PPARγ, suggesting miR-130b may play a key role in the progression of osteosarcoma.

Objective To explore the clinical characteristics of autoimmune disease with dual seropositive antibodies of leucine-rich glioma inactivated 1(LGI1)and contactin-associated protein 2(Caspr2).Methods The clinical data of seven patients with dual seropositive LGI1 and Caspr2 antibodies who were admitted to the Neurology Department of Peking Union Medical College Hospital from July 2014 to December 2017 were retrospectively analyzed.Results Central,peripheral and autonomic nervous systems were all involved in the seven cases;100%(7/7)presented with insomnia,myokymia,neuropahic pain and hyperhydrosis;71%(5/7)showed memory decline or psychiatric and behavioral symptoms;57%(4/7)had urinary hesitation or constipation;and 43%(3/7)had seizure.Electromyography showed 100%(6/6) of the patients had prolonged afterdischarges following normal M waves and/or abnormal spontaneous firing.Electroencephalography revealed slow waves or basic rhythm slowing in 71%(5/7)of patients.Electrocardiography showed sinus tachycardia,axis deviation,and prolonged QT intervals in 71%(5/7)of patients.One patient died from arrhythmia before immunotherapy.One died from pulmonary infection after immunotherapy.Improvement with immunotherapy was documented in the other five cases.No relapse was noted during the 1-2-year follow-up.Conclusions Autoimmune disease with dual seropositive antibodies of LGI1 and Caspr2 can diffusely affect the central,peripheral,and autonomic nervous systems.The possibility of this disease should be considered in patients with acute and subacute onset of neuropsychiatric symptoms,especially in patients with accompanying insomnia,myokymia,and hyperhydrosis.
Autoantibodies ; blood ; Autoimmune Diseases ; immunology ; Humans ; Membrane Proteins ; immunology ; Nerve Tissue Proteins ; immunology ; Proteins ; immunology ; Retrospective Studies