Role of irisin in bone diseases.

Bone diseases are common among middle-aged and elderly people, and harm to activities of daily living (ADL) and quality of life (QOL) for patients. It is crucial to search for key regulatory factors associated with the development of bone diseases and explore potential therapeutic targets for bone diseases. Irisin is a novel myokine that has been discovered in recent years. Accumulating evidence indicates that irisin has beneficial effects in the treatment of various diseases such as metabolic, cardiovascular and neurological disorders, especially bone-related diseases. Recent studies had shown that irisin plays the role in various bone diseases such as osteoarthritis, osteoporosis and other bone diseases, suggesting that irisin may be a potential molecule for the prevention and treatment of bone diseases. Therefore, in this review, by consulting the related domestic and international literature of irisin and bone diseases, we summarized the specific regulatory mechanisms of irisin in various bone diseases, and provided a systematic theoretical basis for its application in the diagnosis and treatment of the bone diseases.

Enhanced self-renewal of human long-term hematopoietic stem cells by a sulfamoyl benzoate derivative targeting p18INK4C.

The use of umbilical cord blood transplant has been substantially limited by the finite number of hematopoietic stem and progenitor cells in a single umbilical cord blood unit. Small molecules that not only quantitatively but also qualitatively stimulate enhancement of hematopoietic stem cell (HSC) self-renewal ex vivo should facilitate the clinical use of HSC transplantation and gene therapy. Recent evidence has suggested that the cyclin-dependent kinase inhibitor, p18INK4C (p18), is a critical regulator of mice HSC self-renewal. The role of p18 in human HSCs and the effect of p18 inhibitor on human HSC expansion ex vivo need further studies. Here we report that knockdown of p18 allowed for an increase in long-term colony-forming cells in vitro. We then identified an optimized small molecule inhibitor of p18, 005A, to induce ex vivo expansion of HSCs that was capable of reconstituting human hematopoiesis for at least 4 months in immunocompromised mice, and hence, similarly reconstituted secondary recipients for at least 4 more months, indicating that cells exposed to 005A were still competent in secondary recipients. Mechanistic studies showed that 005A might delay cell division and activate both the Notch signaling pathway and expression of transcription factor HoxB4, leading to enhancement of the self-renewal of long-term engrafting HSCs and the pool of progenitor cells. Taken together, these observations support a role for p18 in human HSC maintenance and that the p18 inhibitor 005A can enhance the self-renewal of long-term HSCs.

A Dynamic Hysteresis Model and Nonlinear Control System for a Structure-Integrated Piezoelectric Sensor-Actuator.

The piezoelectric sensor-actuator plays an important role in micro high-precision dynamic systems such as medical robots and micro grippers. These mechanisms need high-precision position control, while the size of the sensor and actuator should be as small as possible. For this paper, we designed and manufactured a structure-integrated piezoelectric sensor-actuator and proposed its PID (Proportion Integral Differential) control system based on the dynamic hysteresis nonlinear model and the inverse model. Through simplifying the structure of the piezoelectric sensor-actuator by the centralized parameter method, this paper establishes its dynamic model and explores the input-output transfer function by taking the relationship between the output force and displacement as the medium. The experiment shows the maximum distance of the hysteresis curve is 0.26 µm. By parsing the hysteresis curve, this paper presents a dynamic hysteresis nonlinear model and its inverse model based on a 0.5 Hz quasi-static model and linear transfer function. Simulation results show that the accuracy of the static model is higher than that of the dynamic model when the frequency is 0.5 Hz, but the compensation accuracy of the dynamic model is obviously better than that of the static model with the increase of the frequency. This paper also proposes a control system for the sensor-actuator by means of the inverse model. The simulation results indicate that the output root mean square error was reduced to one-quarter of the original, which proves that the structure-integrated piezoelectric sensor-actuator and its control system have a great significance for signal sensing and output control of micro high-precision dynamic systems.

High-Speed Handling Robot with Bionic End-Effector for Large Glass Substrate in Clean Environment.

The development of "large display, high performance and low cost" in the FPD industry demands glass substrates to be "larger and thinner". Therefore, the requirements of handling robots are developing in the direction of large scale, high speed, and high precision. This paper presents a novel construction of a glass substrate handling robot, which has a 2.5 m/s travelling speed. It innovatively adopts bionic end-suction technology to grasp the glass substrate more firmly. The structure design is divided into the following three parts: a travel track, a robot body, and an end-effector. The manipulator can be smoothly and rapidly extended by adjusting the transmission ratio of the reducer to 1:2:1, using only one motor to drive two sections of the arm. This robot can transfer two pieces of glass substrate at one time, and improves the working efficiency. The kinematic and dynamic models of the robot are built based on the DH coordinate. Through the positioning accuracy experiment and vibration experiment of the end-effector, it is found that the robot has high precision during handling. The robots developed in this study can be used in large-scale glass substrate handling.

[Screening and Verification of Antioxidant Small Molecular Compounds for Expansion of Human Hematopoietic Stem Cells Ex Vitro].

OBJECTIVE: To screen the antioxidant small molecular compounds with optimal efficiency of expansing the human hematopoietic stem cells (hHSC) In vitro based on antioxidant small molecular compound database of LKT laboratory, and to verify the effects of these compounds on the biological functions of hHSC. METHODS: The umbilial cord blood CD34+ cells were enriched by using the MACS beads; the absolute number and percentage of CD34+ cells and CD34+ CD49f+ cells were detected by high throughput flow cytometry after culture of hHSC with compounds in vitro for 1 week, the SR1 (1 µmol/L) was used as positive control, the candidate compounds were screened out; then 4 compounds were selected for follow-up experiments by comprehensive evaluation of concentration, safety and expansion efficacy, the optimal used concentrations of selected compounds were determined through the concentration gradient analysis, and CFC short-term colony-forming cell test was performed by using the determined concentration so as to verify the effect of compounds on the self-renewal, multilineage differentiation. RESULTS: Out of 85 antioxidant small molecular compounds, 4 compounds (C2968, D3331, B1753 and B3358) with obvious expansion efficacy for CD34+ cells and CD34+ CD49f+ cells were screened out by high throughput flow cytometry; their optimal concentrations of 4 compounds were 0.5 µmol/L for C2968, 1.5 µmol/L for D3331 and 1.5 µmol/L for B1753 and 15 µmol/L for B3358. The CFC assay showed the colony formation number in compound-treated group significantly increased as compared with control group, moreover the self-renewal and multilineage differentiation were maintained. CONCLUSION: The antioxidant small molecular compounds C2968 (0.5 µmol/L), D3331 (1.5 µmol/L), B1753 (1.5 µmol/L) and B3358 (1.5 µmol/L) possess good expansion efficacy for hHSC, they can maintain hHSC self-renewal, at the same time ensure the multilineage differentiation potentiality of hHSC.

Antineoplastic effects and mechanisms of micheliolide in acute myelogenous leukemia stem cells.

Leukemic stem cells (LSCs) greatly contribute to the initiation, relapse, and multidrug resistance of leukemia. Current therapies targeting the cell cycle and rapidly growing leukemic cells, including conventional chemotherapy, have little effect due to the self-renewal and differentiated malignant cells replenishment ability of LSCs despite their scarce supply in the bone marrow. Micheliolide (MCL) is a natural guaianolide sesquiterpene lactone (GSL) which was discovered in michelia compressa and michelia champaca plants, and has been shown to exert selective cytotoxic effects on CD34+CD38- LSCs. In this study, we demonstrate that DMAMCL significantly prolongs the lifespan of a mouse model of human acute myelogenous leukemia (AML). Mechanistic investigations further revealed that MCL exerted its cytotoxic effects via inhibition of NF-κB expression and activity, and by generating intracellular reactive oxygen species (ROS). These results provide valuable insight into the mechanisms underlying MCL-induced cytotoxicity of LSCs, and support further preclinical investigations of MCL-related therapies for the treatment of AML.

[Ex vivo Culture System of Single Human Hematopoietic Stem Cell Used to Screan the Small Molecular Compounds].

OBJECTIVE: To explore an efficient, stable system and method to verify the regulation effect of small molecule compounds on human hematopoietic stem cells (hHSC). METHODS: By using combination of flow cytometry with study results of surface markers on hHSC, and optimation of sorting process for further studying the effect of small molecular compounds on stem property of hHSC, the single hHSC was treated with published small molecular compounds such as SR1 and UM171 which possess the expansion effect. After treating with hHSC for 14 d, the flow cytometric analysis of cell phenotypes and cell morphologic observation were performed, at the same time the hematopoietic function of cultured hHSC was verified by colony-forming cell (CFC) test and cobblestone area forming cell (CAFC) test. RESULTS: The effects of SR1 and UM171 and their compositions in multi-cell culture were consistent with the published data, therefore the useful concentration of compounds were obtained. The results of multiparameter sorting of single cell (CD34+ CD38- CD45RA- CD90+ CD49f+) and ex vivo culture were consistent with the results of bulk cell culture. The results of cell phenotype analysis was in accordance with flow cytometric results. In addition, CFC test and CAFC test revealed that the colony-forming ability in treated group was significantly higher than that in control group (P<0.05). CONCLUSION: The rapid, efficient stably amplified and short-time culture system for single hHSC and method for varifying the effect of small molecular compounds are established, which provides platform for screening small molecular compounds and lays the foundation for further study of hHSC expansion.