Infiltration of tumor associated macrophages in multiple myeloma and its clinical significance / 中华血液学杂志

Objective: To investigate the clinical significance of tumor associated macrophages (TAM) in multiple myeloma (MM) and the relationship with angiogenesis and immunosuppression. Methods: Seventy cases of MM patients diagnosed from August 2015 to June 2017 were enrolled in the study as experimental group, 20 cases of benign hematological diseases (13 with iron deficiency anemia and 7 with megaloblastic anemia) patients as control group. Immunohistochemical method was used to detect the expression of CD163, CD34 and VEGF in bone marrow samples, and flow cytometry was used to detect the proportion of regulatory T cell (Treg cells), ELISA was used to detect the level of IL-10, and the clinical features were analyzed. Results: ①Among the 70 patients, there were 31 males and 39 females with a median age of 65 (50~78) years old. TAM infiltration density, microvascular density (MVD), VEGF expression level, Treg ratio and IL-10 level in bone marrow samples of 70 MM patients were significantly higher than those of benign hematological diseases (P<0.05). ②In the MM group, the above indexes of the patients with disease stabilized (15 cases) were lower than those of the newly diagnosed group (35 cases) and the relapse refractory group (20 cases) (P<0.05), those of relapse refractory group were higher than those of newly diagnosed group (P>0.05). ③Of the 35 newly diagnosed MM patients, 27 completed 4 courses of treatment. In the effective group (15 cases), the TAM infiltration density after treatment was significantly lower than that before treatment, the difference was statistically significant[(20.20±7.66) vs (28.87±11.97), t=2.362, P=0.025]; while in the ineffective group of 12 cases, the difference of the TAM infiltration density before and after treatment was not statistically significant[(42.00±13.76) vs (48.25±13.59), t=1.119, P=0.275]. ④TAM infiltration density in the effective group after bortezomib treatment (21 cases) were lower than those in the non-bortezomib treatment group (18 cases)[(16.52 ±4.26) vs (19.27 ±5.82), t=1.662, P=0.170]. ⑤The TAM infiltration density in MM patients was positively correlated with MVD, VEGF expression level, Treg cell ratio and IL-10 level (P<0.001). Conclusion: The infiltration of TAM in the microenvironment of MM, which may promoting angiogenesis and inhibiting immune response, is related to the occurrence, development, therapeutic effect and drug resistance of MM.

Effect of chrysin on expression of NOX4 and NF-κB in right ventricle of monocrotaline-induced pulmonary arterial hypertension of rats / 药学学报

The aim of the present study is to investigate the protective effect of chrysin (5,7-dihydroxyflavone) on right ventricular remodeling in a rat model of monocrotaline-induced pulmonary arterial hypertension (PAH). PAH rats were induced by a single injection of monocrotaline (60 mg x kg(-1), sc) and were administered with chrysin (50 or 100 mg x kg(-1) x d(-1)) for 4 weeks. At the end of experiment, the right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure (mPAP) were monitored via the right jugular vein catheterization into the right ventricle. Right ventricle (RV) to left ventricle (LV) + septum (S) and RV to tibial length were calculated. Right ventricular morphological change was observed by HE staining. Masson's trichrome stain was used to demonstrate collagen deposition. The total antioxidative capacity (T-AOC) and malondialdehyde (MDA) levels in right ventricle were determined according to the manufacturer's instructions. The expressions of collagen I, collagen III, NADPH oxidase 4 (NOX4) and nuclear factor-kappa B (NF-κB) were analyzed by immunohistochemisty, qPCR and (or) Western blot. The results showed that chrysin treatment for 4 weeks attenuated RVSP, mPAP and right ventricular remodeling index (RV/LV+S and RV/Tibial length) of PAH rats induced by monocrotaline. Furthermore, monocrotaline-induced right ventricular collagen accumulation and collagen I and collagen III expression were both significantly suppressed by chrysin. The expressions of NOX4, NF-κB and MDA contents were obviously decreased, while the T-AOC was significantly increased in right ventricule from PAH rats with chrysin treatment. These results suggest that chrysin ameliorates right ventricular remodeling of PAH induced by monocrotaline in rats through its down-regulating of NOX4 expression and antioxidant activity, and inhibiting NF-κB expression and collagen accumulation.

Development of ultrasonic viscoelasticity detection system by shear wave dispersion ultrasound vibration / 医用生物力学

Objective To establish an ultrasonic viscoelastic detection system to measure the viscoelasticity of in vitro tissues. Methods Based on the method of shear wave dispersion ultrasound vibration (SDUV), this system applied acoustic radiation force to excite harmonic vibration in soft tissues. The propagation of shear waves induced by the vibration was detected and the tissue viscoelasticity properties were calculated. The standard phantom and rat liver experiment were conducted using this system, and preliminary assessment of the system was completed. Results The measured result of standard phantom was close to the calibration value. The viscous and elastic coefficient of rat liver were (1.12±0.41) Pa•s and (0.81±0.40) kPa, respectively. Conclusions The results about the standard phantom and rat liver experiment approved feasibility of the system for viscoelasticity measurement on in vitro animal experiment, which is a preliminary exploration for the realization of liver fibrosis detection of human body.

Ginsenoside Rg1 antagonizes β-amyloid peptide-induced apoptosis in primarily cultured rat neurons via mitochondrial pathway / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To assess the neuroprotective effects of ginsenoside Rg1 against β-amyloid peptide (Aβ(25-35))-induced apoptosis in primarily cultured rat cortical neurons.</p><p><b>METHODS</b>Primarily cultured cortical neurons were obtained from embryonic (E18d) rat fetus and maintained in neurobasal medium for 7d. Primary neurons pretreated with 1 μmol/L, 10 μmol/L or 20 μmol/L Rg1 for 24 h were challenged with 10 μmol/L Aβ(25-35) for 72 h. Morphological changes of neurons were evaluated; mitochondrial membrane potential (ΔΨm) was measured; with JC-1 staining and the expression of neural apoptosis-related proteins was detected by Western blot analysis.</p><p><b>RESULTS</b>Exposure to Aβ(25-35) for 72 h caused serious neural cell insults. A pretreatment with Rg1 significantly reduced Aβ(25-35)induced cell death in a dose-dependent manner, with a maximal effect (-90%) obtained at 20 μmol/L. The JC-1 staining results demonstrated the loss of ΔΨm after Aβ(25-35) treatment, while Rg1 maintained the normal level of ΔΨm. A series of mitochondrion-mediated apoptotic events happened after Aβ(25-35) treatment, such as decrease of Bcl-2/Bax, release of cytochrome C and activation of caspase 9 and caspase 3, which were all blocked by Rg1 pretreatment. Both estrogen receptor (ER) antagonist ICI182, 780 and glucocorticoid receptor (GR) antagonist RU486 blocked the antiapoptotic effects of Rg1.</p><p><b>CONCLUSION</b>Ginsenoside Rg1 protects primary cultured rat cortical neurons from Aβ(25-35)-induced injury, which may be associated with mitochondrion-mediated antiapoptosis pathway.</p>

Isolation and identification of stem cells derived from human exfoliated deciduous teeth by magnetic activated cell sorting / 南方医科大学学报

<p><b>OBJECTIVE</b>To isolate stem cells from human exfoliated deciduous teeth (SHEDs) and identify their phenotypes and multi-lineage differentiation potential.</p><p><b>METHODS</b>Human pulp tissue from exfoliated deciduous teeth were dissected and digested to obtain the single cell suspension. The SHEDs selected by magnetic activated cell sorting system (MACS) were identified by examination of the cell morphology and growth in vitro and detection of the expressions of the cell markers. Osteogenic and adipogenic induction was performed to test the multi-lineage differentiation potential of the cells.</p><p><b>RESULTS</b>SHEDs were successfully isolated from human exfoliated deciduous teeth. SHEDs showed a lower growth rate than dental pulp cells and displayed high expressions of CD29 and CD105 but low expressions of CD34 and CD45 as shown by flow cytometry. Experiments of in vitro induction demonstrated a strong potential of the STRO-1+ SHEDs for osteogenic and adipogenic differentiation.</p><p><b>CONCLUSION</b>Immunomagnetic bead selection can be used to isolate and purify SHEDs, and the STRO-1+ SHEDs show the characteristics of stem cells with multipotent differentiation potentials.</p>

Osteogenic capacity of human deciduous dental pulp stem cells in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To test the capacity of the stem cells derived from human exfoliated deciduous teeth in in vitro differentiation into osteoblasts.</p><p><b>METHODS</b>Stem cells were isolated from the exfoliated deciduous teeth of healthy children and sorted into CD34(+)/CD117(+) cells and the remaining mixed cells using flow cytometry. After in vitro cell culture, the differentiation capacity into osteoblasts of the two groups of cells was evaluated by detecting the markers of osteoblasts using immunocytochemical techniques and fluorescent quantitative PCR. Mineralization assay was performed to identify the cell differentiation.</p><p><b>RESULTS</b>The cells isolated by typsin digestion grew in the manner of fibroblasts. After a 30-day culture of the two groups of cells, immunocytochemistry detected the expressions of osteoblast markers RUNX-2, OC, and BSP. After 40 days of cell culture, the mRNA expressions of RUNX-2, OC and BSP genes were significantly different between the two groups. At day 50 of cell culture, the CD34(+)/CD117(+) cells exhibited positivity for von Kossa's staining and alizarin red staining, but the mixed cells showed negative staining results.</p><p><b>CONCLUSION</b>The purified CD34(+)/CD117(+) stem cells derived from exfoliated deciduous teeth of healthy children possess the capacity to differentiate into osteoblasts and form calcium deposits and mineralized nodules in vitro.</p>

Recent advances in the applications of ultrasonic microbubbles as gene or drug vectors / 药学学报

With the research and application of the new ultrasound microbubble contrast agents, ultrasonic microbubbles can not only help to image, but they can also be used as genes or drug carriers. The microbubbles as genes or drug carriers can pass across the endothelial cell barrier and release genes and drug under the action of ultrasound field, which achieve target treatment effect. Based on the relevant materials, the bioeffects, early successes with gene and drug delivery, and potential clinical applications are reviewed.

Isolation and identification of stem cells derived from human exfoliated deciduous teeth / 南方医科大学学报

<p><b>OBJECTIVE</b>To isolate and identify stem cells from human exfoliated deciduous teeth (SHED).</p><p><b>METHODS</b>Human pulp tissue were dissected and digested to obtain the single cell suspension. The cell morphology was observed and the clonality of the obtained cells was assessed. The phenotype of the cells was detected by immunohistochemistry and flow cytometry (FCM), and the cell cycle was analyzed. The in vitro differentiation of the cells into adipose tissue and formation of mineralization nodules were evaluated.</p><p><b>RESULTS</b>Clonogenic assay showed the formation of 16-18 clones in every 10(3) plated cells derived from human exfoliated deciduous teeth. These cells were found to express the markers of mesenchymal stem cells with a multipotent differentiation potential.</p><p><b>CONCLUSION</b>The cells isolated from human dental pulp are clonogenic and have multipotent differentiation potential, suggesting their identity of SHED.</p>