Heterogeneous bone-marrow stromal progenitors drive myelofibrosis via a druggable alarmin axis.

Functional contributions of individual cellular components of the bone-marrow microenvironment to myelofibrosis (MF) in patients with myeloproliferative neoplasms (MPNs) are incompletely understood. We aimed to generate a comprehensive map of the stroma in MPNs/MFs on a single-cell level in murine models and patient samples. Our analysis revealed two distinct mesenchymal stromal cell (MSC) subsets as pro-fibrotic cells. MSCs were functionally reprogrammed in a stage-dependent manner with loss of their progenitor status and initiation of differentiation in the pre-fibrotic and acquisition of a pro-fibrotic and inflammatory phenotype in the fibrotic stage. The expression of the alarmin complex S100A8/S100A9 in MSC marked disease progression toward the fibrotic phase in murine models and in patient stroma and plasma. Tasquinimod, a small-molecule inhibiting S100A8/S100A9 signaling, significantly ameliorated the MPN phenotype and fibrosis in JAK2V617F-mutated murine models, highlighting that S100A8/S100A9 is an attractive therapeutic target in MPNs.

Impact of TLR5 and NLRC4 activation on proliferation of different breast cancer cell lines / 中国免疫学杂志

Objective:To explore the impact of TLR5 and NLRC4 activation on the proliferation of different breast cancer cell lines,MCF-7 and MDA-MB-23 i.Methods:Induction,expression,purification and identification of recombiant flagellin,including FliC (activating both TLR5 and NLRC4),FliC△90-97 (unable to activate TLR5),FliC-L3A (unable to activate NLRC4),FliC△90-97:L3A (unable to activate both TLR5 and NLRC4).Using different concentration of recombinant flagellin to stimulate MCF-7 and MDA-MB-231 cell lines,72 h later,the proliferation of tumor cells were detected with CCK8.We also used soft AGAR forming experiments to detect the inhibition ratio of recombinant flagellin on breast cancer cell lines.Briefly,1 000 cells were plated in the 6-well plate,then stimulated with 1 μg/ml recombinant flagellin,14 days later,the number of cloning were counted after crystal violet staining.Results:After stimulation with four recombinant flagellins at the concentration of 0.1 μ,g/ml,the inhibition ratio on MCF-7 reached 30％,and FliC△90-97 were dose-dependent on the inhibition of MCF-7 proliferation.At the concentration of 1 μg/ml,FliC-L3A which only activated TLR5 showed stronger inhibition ratio than FliC.FliC△90-97:L3A which did not activate both TLR5 and NLRC4 also inhibited the proliferation of MCF-7.After adding transfection reagent,four recombinant flagellins showed inhibition effect on MDA-MB-231.Conclusion:Flagellin can inhibit the proliferation of MCF-7 and MDA-MB-231,and the mechanism of inhibition on the proliferation were not TLR5 and NLRC4 pathway dependent.There might exist new mechanisms to explain this phenomenon.

[Changes in ultrastructure and bone morphogenetic protein expression in reconstructed mandibular condylar cartilage under continuous mandibular advancement in adult rats].

OBJECTIVE: This study investigated the reconstructed mandibular condylar cartilage and the ultrastructural variations in mandibular condylar cartilage in adult rats as a result of mandibular advancement. METHODS: Thirty 9-week-old male Sprague-Dawley rats were randomly divided into experimental and control groups. Rats in the experimental group were subjected to mandibular advancement. Rats were sacrificed on days 3, 7, 14, 21, 30. Sections were cut from condyles, and bone morphogenetic protein-2 (BMP-2) expression in condylar cartilage was examined through immunohistochemical analysis. Condylar cartilage samples were harvested, and ultrastructural changes in these samples were observed under Micro-CT and transmission electron microscope. RESULTS: Compared with the control group, the experimental group obviously displayed cartilage hyperplasia in the middle and rear of the condyle. Moreover, the number of BMP-2-positive cells in condylar cartilage and the gray value gradually increased in the experimental group on day 7 of the intervention. Ultrastructural changes, such as karyopyknosis, reduced microfilaments around the nucleus, reduction in size or even disappearance of lipid droplets, swelling of endoplasmic reticulum compartments, broadened and increased extracellular matrix, were observed in the condylar hypertrophic chondrocytes. Micro-CT revealed that the trabecula and the newly formed bone gradually thickened. CONCLUSIONS: Hypertrophic remodeling of the condylar cartilage and high BMP-2 expression are observed in adult rats as a result of continuous mandibular advancement.

Research progress of mTOR inhibitors in the treatment of breast cancer / 肿瘤研究与临床

Although the treatment has made great progress in breast cancer, there are still many problems. For example, primary or secondary on chemotherapy drug resistance and the limitation of treatment in triple-negative breast cancer. So, targeted therapy has become a new strategy to improve this situation. Previous studies showed that the occurrence of breast cancer may be related to the activation of PI3K/Akt/mTOR signaling pathways, and mTOR is an index to judge the prognosis. Parts of breast cancers can obtain clinical benefit with mTOR inhibitors, and it might be a potential treatment target in breast cancer.

Thinking about the teaching of laboratory diagnosis / 中华医学教育探索杂志

Contents of laboratory diagnosis is complex.Traditional teaching method cannot arouse students' interest in study and the teaching effect is poor. Teachers should choose different teaching emphasis for students in different specialty,increase and decrease theory teaching contents according to the demands of students' future actual work,introduce case analysis,train students' capability of clinical logical thinking,enhance students' perceptual knowledge of theory through the training of experiment skills and using PBL teaching method to make students truly participate in teaching course so as to arouse their enthusiasm,These reforming measures will benefit the improvement of teaching quality.

Targeted therapy for triple-negative breast cancer / 国际肿瘤学杂志

Triple-negative breast cancer(TNBC)is a special subtype of breast cancer which is invalid to endocrine therapy.Anti-Her2 targeted therapies such as herceptin and lapatinib are not suitable to TNBC.At present,conventional chemotherapy is the only way for the medical therapy of TNBC.Thus,searching for novel therapeutic agents for TNBC is one of hot researches of breast cancer.New targeted therapy drugs such as PARP-1 inhibitors,EGFR inhibitors,CXCR4 inhibitors,anti-angiogenesis drugs,Src tyrosine kinase inhibitor,and mTOR inhibitor are being researched.

The Effects of GAPS on Inhibiting Gastric Cancer Cell Line MGC -803 Proliferation and PDGFR - B Expression / 医学研究杂志

Objective To study the effects of ganoderma applanatum polysaccharides(GAPS) on cell morphology, proliferation and PDGFR -?expression in cell lines MGC - 803 , and to explore its potential mechanisms of anti - tumor of GAPS. Methods Cell morphology was observed by inverting microscope. MTT assay was used to investigate the inhibitory effect of GAPS on MGC -803.Expressions of PDGFR -?was analyzed by flow cytometry (FCW). The fluorescence intensity of expressions of PDGFR -?was observed by fluorescence microscope. Results Cells of GAPS group were irregular shaped and grew poorly. GAPS inhibited the proliferation of MGC -803 cells in dose - dependent and time - dependent manners . After MGC - 803 cells were treated with GAPS for 72h, GAPS could down - regulate expression of PDGFR -?observed by fluorescence microscope which was consistented with the results of FCW with statistic significance difference as compared with control group (P

Correlation between ?_2-adrenergic receptor gene Arg16Gly variation and blood-lipid and apolipoprotein ratio mediated by high carbohydrate/low fat diet in healthy young females / 第三军医大学学报

Objective To study the effects of ?2-adrenergic receptor gene Arg16Gly polymorphism on blood lipid and apolipoprotein ratio and its role in blood lipid and apolipoprotein ratio mediated by high carbohydrate/low fat (HC/LF) diet in healthy young persons.Methods Fifty-six healthy young volunteers had regular diet for 7 d followed by HC/LF diet for 6 d.Twelve-hour fasting venous blood samples were collected on days 1,8 and 14 to measure blood lipid and apolipoprotein (apo) AI and B100 levels,and to calculate ratios of TG/HDL-C,log (TG/HDL-C),TC/HDL-C,LDL-C/HDL-C and apoAI/apoB100.DNA was isolated from genome.Arg16Gly polymorphism was analyzed by PCR-RFLP.Results No significant difference was found in the baseline lipid and apolipoprotein ratio in subjects with AA genotype and G carriers before and after regular or HC/LF diet.The ratios of TG/HDL-C (P=0.017),log (TG/HDL-C) (P=0.031),and apoAI/apoB100 (P=0.006) were significantly higher,while those of TC/HDL-C (P=0.001) and LDL-C/HDL-C (P

Radioligand binding assay of insulin receptor in rabbit kidney during ischemia and reperfusion / 中国病理生理杂志

AIM: To observe the change of insulin receptor in rabbit kidney with acute ischemic-reperfusion injury. METHODS: 15 Japanese white rabbits were allocated randomly into control group, ischemic-reperfusion group(IR group). IR group received clamping for 1 h followed by 2 h or 48 h of reperfusion. At 2 h or 48 h after reperfusion, glucose and insulin in serum were determined. Insulin receptor in renal tissue was analyzed by radioligand binging assay(BAD). RESULTS: The level of serum glucose increased after 2 h reperfusion in 2 groups, but in IR group the value increased much more higher than those in control groups(P