Application of serum pharmacology in evaluating the antitumor effect of Fuzheng Yiliu Decoction from Chinese medicine / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the feasibility of serum pharmacology in evaluating the antitumor effect of Chinese medicine (CM) of Fuzheng Guben (supporting the healthy energy and strengthening the body's resistance to pathogens), the effects of Fuzheng Yiliu Decoction (FYD), a typical prescription of Fuzheng Guben, on proliferation and apoptosis of hepatoma cells in vitro were observed by two methods with serum pharmacology and traditional pharmacology, respectively.</p><p><b>METHODS</b>HepG2 cells were treated with FYD-containing serum or crude FYD extract in vitro. The proliferation rate was determined by methyl thiazolyl tetrazolium (MTT) assay. Cell cycle and apoptosis rate was performed by flow cytometry. And the levels of interleukin-2 (IL-2) and tumor necrosis factor α (TNF-α) in FYD-containing serum were detected by radioimmunoassay.</p><p><b>RESULTS</b>FYD-containing serum remarkably inhibited proliferation and induced apoptosis of hepatoma cells at least by promoting the production of IL-2 and TNF-α in vivo. On the contrary, crude FYD extract promoted the proliferation and did not induce cell apoptosis.</p><p><b>CONCLUSION</b>The results by serum pharmacology were accordant with those of our previous animal and clinical trials which indicates that serum pharmacology is a reasonable and feasible method for the evaluation of the antitumor effect of herbs of Fuzheng Guben.</p>

Hydrogen peroxide preconditioning enhances the therapeutic efficacy of Wharton's Jelly mesenchymal stem cells after myocardial infarction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Exposure of cells to sublethal concentrations of hydrogen peroxide (H2O2) can alleviate subsequent oxidative stress-induced apoptosis. We assessed the effects of H2O2 preconditioning on the therapeutic potential of human umbilical cord Wharton's Jelly mesenchymal stem cells (WJ-MSCs) in a murine model of myocardial infarction.</p><p><b>METHODS</b>WJ-MSCs were incubated in the media for 2 hours with or without 200 µmol/L H2O2. Mice underwent left anterior descending coronary artery ligation, and received injection of phosphate buffered saline, 1×10(6) WJ-MSCs, or 1×10(6) H2O2 preconditioned WJ-MSCs 3 hours later via tail vein. Echocardiography was performed 0, 7, 14 and 28 days after surgery, and the mice were euthanized on day 28 for histological analysis. In vitro cytokine concentrations in the WJ-MSC cell supernatant were measured by enzyme-linked immunosorbent assay (ELISA). The effect of WJ-MSC cell supernatant on the migration and proliferation of endothelial cells were observed by transwell migration and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide (MTT) assays.</p><p><b>RESULTS</b>Echocardiographic measurements revealed a significant improvement in the left ventricular contractility of the WJ-MSCs-H2O2 group compared to the WJ-MSCs group. Histological analysis revealed increased neovascularization and reduced myocardial fibrosis in the WJ-MSCs-H2O2 group compared to the WJ-MSCs group. Pretreatment of WJ-MSCs with H2O2 increased the secretion of interleukin-6 (IL-6) into the cell culture supernatant by approximately 25-fold. The culture supernatant from WJ-MSCs-H2O2 significantly increased the migration and proliferation of endothelial cells; these effects could be blocked using an anti-IL-6 antibody.</p><p><b>CONCLUSIONS</b>This study demonstrates that H2O2 preconditioning significantly enhanced the therapeutic potential of WJ-MSCs, possibly by stimulating the production of IL-6 by WJ-MSCs, which may cause migration and proliferation of endothelial cells and increase neovascularization.</p>

Fuzheng Yiliu Granule inhibits the growth of hepatocellular cancer by regulating immune function and inducing apoptosis in vivo and in vitro / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the inhibitory effect of Fuzheng Yiliu Granule (FYG) on hepatocellular cancer (HCC) and investigate the mechanism mediating its bioactivity.</p><p><b>METHODS</b>H22 tumor-bearing ICR mice were treated with FYG [3.6 g/(kg·d)] for 5 days. Tumor volume and tumor weight, percentages of CD3(+), CD4(+), CD8(+), and natural killer (NK) cells in peripheral blood, tumor apoptosis and serum levels of interleukin-2 (IL-2), and tumor necrosis factor-α (TNF-α) were evaluated. FYG-containing serum was prepared from SD rats treated for 7 days [high dose 3.6 g/(kg·d); middle dose 1.8 g/(kg·d); low dose 0.9 g/(kg·d)]. Cell cycle, cell viability, and apoptosis were evaluated after HepG2 cell line was cultured in FYG-containing serum for 48 h. The levels of IL-2 and TNF-α in FYG-containing serum were also determined.</p><p><b>RESULTS</b>FYG produced a potent antitumor effect (P<0.01) and induced marked apoptosis of the tumor tissue (P<0.05). Mice treated with FYG had higher percentages of CD3(+) and CD4(+) (P<0.05), and more NK cells (P<0.01) in the peripheral blood than those in the animals treated with normal saline. Mice receiving FYG had the highest serum levels of IL-2 and TNF-α (P<0.01). High-dose FYG-containing serum significantly decreased HepG2 cell viability, inhibited cell proliferation (P<0.05), and induced apoptosis (P<0.01). In addition, the levels of IL-2 and TNF-α of high-dose-containing serum were higher than the blank serum (P<0.01).</p><p><b>CONCLUSION</b>FYG could inhibit HCC growth by regulating immune function and inducing apoptosis of tumor cells in vivo and in vitro.</p>

Flk1+ mesenchymal stem cells ameliorate carbon tetrachloride-induced liver fibrosis in mice / 生物工程学报

Fibrosis is the common end stage of most liver diseases. Unfortunately, there is no effective treatment available currently. This study was designed to evaluate the effect of Flk1+ mesenchymal stem cells (MSC) from murine bone marrow (Flk1 + MSC) on fibrosis formation induced by carbon tetrachloride (CCl4). In this study Flk1+ MSC were isolated from bone marrow of male BALB/c mice. A CCl4 induced hepatic fibrosis model was used. Flk1+ MSC were systemically infused immediately or one week after the female mice were challenged with CCl4. Fibrosis index and donor cell engraftment were assessed two or five weeks after CCl4 challenge. We found that Flk1+ MSC transplantation immediately, but not one week after exposure to CCl4, significantly reduced CCl4-induced liver damage and collagen deposition. In addition, levels of hepatic hydroxyproline and serum fibrosis markers (HA, P-III-P) in mice receiving immediate Flk1+ MSC transplantation after CCl4 challenge were significantly lower compared to those of control mice. More importantly, histological examination suggested that hepatic damage recovery was much better in these immediately Flk1+ MSC-treated mice. Immunofluorescence, PCR, and fluorescence in situ hybridization (FISH) analysis revealed that donor cells engrafted into host liver, had epithelium-like morphology and expressed albumin (ALB), although at low frequency. In conclusion Flk1+ MSC might initiate endogenous hepatic tissue regeneration, engraft into host liver in response to CCl4 injury, and ameliorate its fibrogenic effects.

Application of mesenchymal stem cell in immunotherapy--review / 中国实验血液学杂志

There has been an increasing interest in recent years on mesenchymal stem cell (MSC). It is well known that MSCs are capable of self-renewal and differentiating into many cell lineages. MSC can be expended to a large quantity that is required for clinical transplantation. Recent studies show that MSC have potential application in immune diseases due to their unique immunologic characteristics, such as low immunogenicity and immunoregulatory function. But their immunoregulatory mechanism is not yet clear. This review discusses the advances in researches on the mechanism of MSCs' immunoregulatory function and potential clinical application in immune disease and organ transplantation.

Potential of human adipose tissue derived adult stem cells differentiate into endothelial cells / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate whether human adipose derived adult stem (hADAS) cells can differentiate into endothelial cells.</p><p><b>METHODS</b>Stem cells were isolated and expanded from adipose tissue and then induced to differentiate into cells of osteogenic, adipogenic and neurogenic lineages in vitro. hADAS cells were induced with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) to endothelial cells differentiation. hADAS cells were intravenously injected into mouse hindlimb ischemic models to test their ability to differentiate endothelial cells in vivo.</p><p><b>RESULTS</b>hADAS cells were easily isolated and expanded in vitro. They had the ability to differentiate into osteogenic, adipogenic and neurogenic lineages. The cells expressed vascular endothelial growth factor receptor-2 (VEGFR-2, Flk1), and expressed endothelial markers when cultured with VEGF and bFGF. In response to local cues, hADAS cells in vivo differentiate into endothelial cells that contributed to neoangiogenesis in hindlimb ischemia models.</p><p><b>CONCLUSIONS</b>Flk1+ hADAS cells have multipotential not only similar to bone marrow mesenchymal stem cells, but also exhibiting characteristics of endothelial progenitor cells. They may be a potential source of endothelial cells for cellular pro-angiogenic therapies.</p>

Improvement of cardiac function after transplantation of autologous bone marrow mesenchymal stem cells in patients with acute myocardial infarction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The infarct size determines the long-term prognosis of patients with acute myocardial infarction (AMI). There is a growing interest in repairing scar area by transplanting bone marrow stem cells. However, effectiveness of intracoronary injection of bone marrow mesenchymal stem cells (BMSCs) in patients with AMI still remains unclear.</p><p><b>METHODS</b>Sixty-nine patients with AMI after percutaneous coronary intervention (PCI) were randomly divided into intracoronary injection of BMSCs (n = 34) and saline (control group, n = 35) groups. Serial single positron emission computer tomography (SPECT), cardiac echo and cardiac electromechanical mapping were done at the designed time intervals until six months after transplantation of BMSCs or injection of saline.</p><p><b>RESULTS</b>The proportion with functional defect decreased significantly in the BMSCs patients after three months [(13 +/- 5)%] compared with that pre-transplantation [(32 +/- 11)%] and the control group [(28 +/- 10)%] at three month follow-up (P < 0.05, respectively). Wall movement velocity over the infracted region increased significantly in the BMSCs group [(4.2 +/- 2.5) cm/s vs (2.2 +/- 1.3) cm/s, P < 0.05], but not in the control group [(2.2 +/- 1.5) cm/s vs (2.7 +/- 1.7) cm/s, P > 0.05]. Left ventricular ejection fraction (LVEF) three months after transplantation in BMSCs group increased significantly compared with that pre-implantation and with that of the control group at three months post-injection [(67 +/- 11)% vs (49 +/- 9)% and (53 +/- 8)%, P < 0.05 respectively]. SPECT scan results showed that perfusion defect was improved significantly in BMSCs group at three-month follow-up compared with that in the control group [(134 +/- 66) cm(2) vs (185 +/- 87) cm(2), P < 0.01]. At the same time, left ventricular end-diastolic volume [(136 +/- 31) ml vs (162 +/- 27) ml, P < 0.05] and end-systolic volume [(63 +/- 20) ml vs (88 +/- 19) ml, P < 0.05] decreased synchronously. The ratio of end-systolic pressure to end-systolic volume [Psyst/ESV, (2.84 +/- 1.30) mmHg/ml vs (1.72 +/- 1.23) mmHg/ml, P < 0.05] increased significantly. Cardiac electromechanical mapping demonstrated significant improvement at three months after implantation of BMSCs compared with that pre-injection in both cardiac mechanical capability as left line local shorting [LLS, (11.29 +/- 1.64)% vs (7.32 +/- 1.86)%, P < 0.05] and electrical property as left ventricular endocardial unipolar voltage [UV, (10.38 +/- 1.12) mV vs (7.61 +/- 1.09) mV, P < 0.01]; perfusion defect decreased from (36.2 +/- 6.2)% to (20.3 +/- 5.31)% (P < 0.01). Twenty-four-hour electrocardiographic monitoring demonstrated no arrhythmias occurred at three-months follow-up.</p><p><b>CONCLUSIONS</b>The transplantation of BMSCs might improve the cardiac function and it is safe and feasible with no deaths or malignant arrhythmias.</p>

Association of some SNP in TGFA,IRF6 and nonsyndromic cleft lip with or without cleft palate by DNA microarray technology / 中华检验医学杂志

Objective To explore the relationship between some single nucleotide polymorphisms (SNP)loci of interferon regulatory factor 6(IRF6)gene,transforming growth faetor-?(TGFA)gene and nonsyndromic cleft lip with or without cleft palate(NSCL/P)in nuclear families consisting of fathers, mothers and affected offspring with NSCL/P from southeast China.Methods Some SNloci of IRF6 and TGFA were detected by applying microarray technology in nuclear families,and then haplotype relative risk (HRR)and transmission disequilibrium test(TDT)were performed.Results There were no significant difference in genotypes and alleles distribution between patients and their parents.The SNP locus——V274I of IRF6 was associated with NSCL/P(HRR:?~2=4.5816,P