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Acute myeloid leukaemia (AML) is a clinically and molecularly heterogeneous disease characterised by uncontrolled proliferation, block in differentiation and acquired self-renewal of hematopoietic stem and myeloid progenitor cells. This results in the clonal expansion of myeloid blasts within the bone marrow and peripheral blood. The incidence of AML increases with age, and in childhood, AML accounts for 20% of all leukaemias. Whilst there are many clinical and biological similarities between paediatric and adult AML with continuum across the age range, many characteristics of AML are associated with age of disease onset. These include chromosomal aberrations, gene mutations and differentiation lineage. Following chemotherapy, AML cells that survive and result in disease relapse exist in an altered chemoresistant state. Molecular profiling currently represents a powerful avenue of experimentation to study AML cells from adults and children pre- and postchemotherapy as a means of identifying prognostic biomarkers and targetable molecular vulnerabilities that may be age-specific. This review highlights recent advances in our knowledge of the molecular profiles with a focus on transcriptomes and metabolomes, leukaemia stem cells and chemoresistant cells in adult and paediatric AML and focus on areas that hold promise for future therapies.
Polydioxanone (PDO) threads, poly-L-lactic acid (PLLA) threads, and polycaprolactone (PCL) threads have been used for lifting and antiaging purposes. The new PCL threads that have less residual monomer compared to the previous PCL are developed.
The efficacy of threads regarding collagen synthesis and wrinkle improvement was evaluated in vivo model.
In this study, threads were inserted into 30 six-week-old male SKH-1 hairless mice. One of four threads was implanted at either side of the spine of each mouse. Biopsy specimens obtained at 1, 4, and 8weeks were examined using hematoxylin and eosin (H&E) and Herovici's stain. Additionally, immunoblot analysis was performed using primary antibody for collagen type III and transforming growth factor-β (TGF-β) and visualized by chemiluminescence and densitometric quantification. Finally, skin replicas were used to calculate total wrinkle area (mm
).
Neocollagenesis was significantly increased by 50% in the new PCL and pre-existing PCL groups at 8weeks (p value<0.001). Additionally, new-PCL-implanted mice showed a significant increase in collagen type III and TGF-β expressions at 8weeks (p value<0.001). The number of inflammatory cells was also increased in the skin of PCL-implanted mice at 8weeks. Finally, wrinkles were reduced about 20% in the new PCL group at 8weeks.
The new PCL thread exhibited a superior skin rejuvenation effect. This suggests that the material processing technology can be applied not only to the thread but also to various products such as dermal filler and cosmetics.
The new PCL thread exhibited a superior skin rejuvenation effect. This suggests that the material processing technology can be applied not only to the thread but also to various products such as dermal filler and cosmetics.
Type2 diabetes mellitus is a group of metabolism abnormalities in carbohydrates and energy. Our aim was to investigate resting energy expenditure (REE) and blood glucose changes after biliary diversion in mice with diabetes.
Male mice with diabetes were randomly divided into biliary diversion and sham groups. REE was detected by indirect calorimetry, the levels of fasting blood glucose, total bile acids and triiodothyronine were analyzed. After mice were killed, the weight amount of brown adipose tissue (BAT) and gastrocnemius was measured, and the expression level of Gprotein-coupled bile acid receptor and type2 iodothyronine deiodinase in BAT and gastrocnemius were examined.
The two groups of mice were pair-fed, the bodyweights (P<0.001) and the fasting blood glucose level (P<0.001) in the biliary diversion group significantly decreased 24weeks after surgery. The intraperitoneal glucose tolerance test (P=0.035) and oral glucose tolerance test (P=0.027) showed improvement in glucose tolerance after surgery. The REE level significantly increased 24weeks after surgery (P=0.005), the levels of total bile acids (P=0.014) and triiodothyronine (P<0.001) increased at the 24th postoperative week. The weight ratio of BAT (P=0.038) and gastrocnemius (P=0.026) in the biliary diversion group were higher than that in the sham group. The expression of Gprotein-coupled bile acid receptor in BAT (P<0.001) and gastrocnemius (P=0.003) were upregulated after surgery, and the type2 iodothyronine deiodinase expression also increased in BAT (P=0.015) and gastrocnemius (P=0.015).
The REE level increased and the glucose metabolism improved in mice with diabetes after biliary diversion.
The REE level increased and the glucose metabolism improved in mice with diabetes after biliary diversion.
Human coagulation factor (F) XI deficiency, a defect of the contact activation system, protects against venous thrombosis, stroke, and heart attack, whereas FXII, plasma prekallikrein, or kininogen deficiencies are asymptomatic. FXI deficiency, inhibition of FXI production, activated FXI (FXIa) inhibitors, and antibodies to FXI that interfere with FXI/FXII interactions reduce experimental thrombosis and inflammation. FXI inhibitors are antithrombotic in patients, and FXI and FXII deficiencies are atheroprotective in apolipoprotein E-deficient mice.
Investigate the effects of pharmacological targeting of FXI in experimental models of atherogenesis and established atherosclerosis.
Low-density lipoprotein receptor-knockout (Ldlr
) mice were administered high-fat diet (HFD) for 8weeks; concomitantly, FXI was targeted with anti-FXI antibody (14E11) or FXI antisense oligonucleotide (ASO). 14E11 and FXI-ASO reduced atherosclerotic lesion area in proximal aortas when compared with controls, and 14E11 also reduced aortic sinus lesions. selleckchem In an established disease model, in which therapy was given after atherosclerosis had developed, Ldlr
mice were fed HFD for 8weeks and then administered 14E11 or FXI-ASO weekly until 16weeks on HFD. In this established disease model, 14E11 and FXI-ASO reduced atherosclerotic lesion area in proximal aortas, but not in aortic sinus. In cultures of human endothelium, FXIa exposure disrupted VE-Cadherin expression and increased endothelial lipoprotein permeability. Strikingly, we found that 14E11 prevented the disruption of VE-Cadherin expression in aortic sinus lesions observed in the atherogenesis mouse model.
Pharmacological targeting of FXI reduced atherogenesis in Ldlr
mice. Interference with the contact activation system may safely reduce development or progression of atherosclerosis.
Pharmacological targeting of FXI reduced atherogenesis in Ldlr-/- mice. Interference with the contact activation system may safely reduce development or progression of atherosclerosis.
Website: https://www.selleckchem.com/products/ml349.html
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