Hypoxia promotes differentiation of human induced pluripotent stem cells into embryoid bodies in vitro / 南方医科大学学报

OBJECTIVE@#To investigate effects of physiological hypoxic conditions on suspension and adherence of embryoid bodies (EBs) during differentiation of human induced pluripotent stem cells (hiPSCs) and explore the underlying mechanisms.@*METHODS@#EBs in suspension culture were divided into normoxic (21% O2) and hypoxic (5% O2) groups, and those in adherent culture were divided into normoxic, hypoxic and hypoxia + HIF-1α inhibitor (echinomycin) groups. After characterization of the pluripotency with immunofluorescence assay, the hiPSCs were digested and suspended under normoxic and hypoxic conditions for 5 days, and the formation and morphological changes of the EBs were observed microscopically; the expressions of the markers genes of the 3 germ layers in the EBs were detected. The EBs were then inoculated into petri dishes for further culture in normoxic and hypoxic conditions for another 2 days, after which the adhesion and peripheral expansion rate of the adherent EBs were observed; the changes in the expressions of HIF-1α, β-catenin and VEGFA were detected in response to hypoxic culture and echinomycin treatment.@*RESULTS@#The EBs cultured in normoxic and hypoxic conditions were all capable of differentiation into the 3 germ layers. The EBs cultured in hypoxic conditions showed reduced apoptotic debris around them with earlier appearance of cystic EBs and more uniform sizes as compared with those in normoxic culture. Hypoxic culture induced more adherent EBs than normoxic culture (P < 0.05) with also a greater outgrowth rate of the adherent EBs (P < 0.05). The EBs in hypoxic culture showed significantly up-regulated mRNA expressions of β-catenin and VEGFA (P < 0.05) and protein expressions of HIF-1 α, β-catenin and VEGFA (P < 0.05), and their protein expresisons levels were significantly lowered after treatment with echinomycin (P < 0.05).@*CONCLUSION@#Hypoxia can promote the formation and maturation of suspended EBs and enhance their adherence and post-adherent proliferation without affecting their pluripotency for differentiation into all the 3 germ layers. Our results provide preliminary evidence that activation of HIF-1α/β-catenin/VEGFA signaling pathway can enhance the differentiation potential of hiPSCs.

Exposure to Radon and Kidney Cancer: A Systematic Review and Meta-analysis of Observational Epidemiological Studies / 生物医学与环境科学（英文）

OBJECTIVE@#To evaluate the possible association between radon exposure and kidney cancer.@*METHODS@#We performed a systematic review and a meta-analysis based on random effect models to provide a pooled association measure.@*RESULTS@#We subjected 8 studies (overall relative risks and 95% confidence intervals: 1.01, 0.72 to 1.43, I2 = 64.4%) to meta-analysis. Subgroup analysis revealed a marginally significant association between radon exposure and kidney cancer in studies conducted in Europe. Two population-based studies provided no evidence for the increased risk of kidney cancer in the general population.@*CONCLUSION@#The association between radon and kidney cancer remains unclear but cannot be excluded because of its biological plausibility and the limited number and quality of existing studies. Additional data from the general population and well-designed miner cohort studies are needed to reveal the real relationship between radon exposure and kidney cancer.

Possible effect of N-acetyl-leu-leu-norleucinal, an inhibitor of Calpain, on H2O2-induced damage in 661W cells / 中国药理学通报

Aim To investigate the possible effect of N-acetyl-leu-leu-norleucinal (ALLN),an inhibitor of Calpain,on H2O2-induced damage in 661W cells.Methods The cellular survival of 661W treated with different doses of H2O2 without or with ALLN for 24 h was measured by MTT assay.The protein level of Calpain 1 and Calpain 2 was assessed by Western blot.Results Upon the H2O2 treatment at the concentrations of 50,100,500,1 000 μmol · L-1,the survival rate of 661W significantly decreased in a dose-dependent manner compared to that of the control group.Furthermore,the protein level of Calpain 1 and Calpain 2 showed an obviously time-dependent increase in 661W cells treated with 100 μmol · L-1 H2O2 for 12,18,24 h.Finally,the survival rate of 661W treated with ALLN and H2O2 was higher than that treated only with H2O2,and there was no difference in survival rate between ALLN groups (at the concentrations of 25,50,100,200 μmol · L-1) and control group.Conclusions Calpain is involved in the damage induced by H2O2.ALLN,the inhibitor of Calpain,attenuates the oxidative damage,which plays a promising protective role in photo-receptor cells under oxidative stress.

Role of Exosomes in the Cross-Talk between Leukemia Cells and Mesenchymal Stem Cells -Review / 中国实验血液学杂志

More and more studies have demonstrated that bone marrow microenvironment, the fundament of the multiplication and differentiation of hematopoietic stem cells, plays a crucial role in leukemia progression and resistance to treatment. It provides a permissive environment for minimal residual disease and contributes to relapse and multidrug resistance. Mesenchymal stem cells are a kind of important stromal cells in bone marrow niche. In recent researches, MSC have been shown to be one of the major factors modulating the biological features of leukemia cells. The cross-talk between MSC and leukemia cells can take place not only by direct contact, but also by exosome exchange. Exosomes are nano-sized vesicles released by a variety of cells, which contain protein, RNA and mRNA. They are effective tools for transportation between cells, and play an important role in many physiological and pathological processes. Exosome is a new topic in the research of leukemia and microenvironment. The exosome research will help elucidate the mechanism of leukemia, thus providing new ideas for the treatment.

Role of Bone Marrow Mesenchymal Stem Cells in Resistance of Chronic Myeloid Leukemia to Tyrosine Kinase Inhibitors -Review / 中国实验血液学杂志

Chronic myeloid leukemia (CML) is a disease originated from malignant hematopoietic stem cell disorder. In CML, mesenchymal stem cells(MSC) have been changed in the bone marrow microenvironment, which can protect the leukemia cells from apoptosis induced by tyrosine kinase inhibitors (TKI) and lead to the resistance to TKI by the secretion of soluble factors, involvement in cell-cell adhesion, and so on. This review mainly focuses on the changes of the bone marrow mesenchymal stem cells in CML, as well as the role and mechanism of MSC in the CML resistance of TKI. The concrete probrems dicussing in this review are role of MSC in bone marrow microenviroment, characteristics of MSC in CML, the related mechanisms of MSC in drug resistance and so on.

Research Progress on TKI Resistance of CML Cells Mediated by MSC through CXCL12/CXCR4 Axis / 中国实验血液学杂志

Although the tyrosinekinase inhibitors (TKI) displayed a significant curative effect on chronic myeloid leukemia (CML), but the drug resistance in treatment course of this disease still can not be avoided. Studies recently have shown that the mesenchymal stem cells (MSC) can induce CML cells to resist TKI therapy by CXCL12/CXCR4 axis from multiple aspects, such as the directional migration of CML cells, adherence to marrow cavity, the mediation of cell protective dormancy, activations of numerous survival signaling pathways, the suppression of mitochondrial-dependent apoptosis and the up-regulated expression of BCL-6. The combination of TKI and CXCR4 antagonists will be a novel treatment strategy to raise the genetic cure rate of CML. In this article, the pathways of drug resistance, pathways of sensitivity to CXCL12 and pathways of CML cell adherence to marrow cavity in CML cells mediated by MSC were reviewed.

Study on the potentiation of bone marrow mesenchymal stem cells involved in sebaceous duct formation / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the feasibility of differentiation of bone marrow mesenchymal stem cells (MSCs) into skin appandence.</p><p><b>METHODS</b>Porcine MSCs were isolated from porcine marrow and grown in vitro. After labeling with BrdU, MSCs were engrafted to porcine skin. At 1, 2, 4 weeks after the transplantation, immunohistochemical examinations were carried out to detect the positive staining of BrdU and cytokeratin.</p><p><b>RESULTS</b>A few sebaceous duct cells, which expressed cytokeratin, were also BrdU positive, and these cells were considered may to be transplanted MSCs-derived cells.</p><p><b>CONCLUSION</b>Porcine MSCs might have the potential to differentiated into sebaceous duct cells in skin.</p>

Effect of hepatitis B vaccine immunization on HBV associated nephritis in children / 中华儿科杂志

<p><b>OBJECTIVE</b>Hepatitis B has been extensively prevalent in China and hepatitis B virus associated nephritis (HBV-GN) has been one of the common renal damages secondary to HBV infection in Chinese children. Regular vaccination against hepatitis B has been carried out nation-wide in China since January 1st, 1992. The present study was conducted to evaluate the effect of regular vaccination against hepatitis B virus on the incidence of childhood HBV-GN and membranous nephropathy (MN).</p><p><b>METHODS</b>Retrospective analysis on the results of renal biopsy in 727 patients (from Nov. 1979 to March 2002) was carried out. The patients were first divided into two groups according to the date when the patients were seen. Group A patients were seen from Nov. 1979 through Dec. 1991; Group B patients were seen from Jan. 1992 through March 2002. Group B patients were further divided into 5 subgroups (Group B(1) to B(5)), with a 2-year interval after 1992. Secondly, each of these groups and subgroups were again divided into two groups, vaccinated and unvaccinated groups.</p><p><b>RESULTS</b>In 727 renal biopsies, 64 cases (8.80%) met HBV-GN diagnostic criteria. Twenty-eight cases were diagnosed as HBV-GN in Group A (211 cases), accounting for 13.27%, while there were 36 cases with HBV-GN in 516 renal biopsies of Group B, accounting for 6.98% (chi(2) = 7.397 and P < 0.01). The frequency in Group B was significantly lower. Prevalence rate (from Group A to Group B(5)) was 13.3% (28/211), 13.0% (9/69), 7.3% (6/82), 6.3% (4/64), 4.9% (4/82), 5.9% (13/219), respectively, which showed a tendency of decline. Only 8 cases of HBV-GN occurred in vaccinated group (231 cases), accounting for 3.5%, while 48 cases of HBV-GN were seen in unvaccinated group (381 cases), accounting for 12.6% (chi(2) = 14.44 and P < 0.001), vaccination history was unknown in 115 of the 727 cases. In 727 renal biopsies, pathological type of 46 cases (6.3%) was membranous nephropathy and all of them had HBV-GN. Six cases of MN occurred in vaccinated group, accounting for 2.60%, while 40 cases with membranous nephropathy were found in unvaccinated group, accounting for 10.5% (chi(2) = 12.92 and P < 0.001). On the other hand, in vaccinated group there still were 8 cases of HBV-GN whose serum markers of HBV were positive. Two of their mothers had apparent evidence of hepatitis B virus infection.</p><p><b>CONCLUSION</b>The frequency of HBV-GN has decreased significantly after vaccination against hepatitis B virus was routinely carried out since 1992; at the same time, childhood membranous nephropathy might be decreasing gradually, too. The cause of individual cases of HBV-GN who has be vaccinated was probably due to maternal-infant transmission and immunization failure. Attention should be paid to interruption of maternal-infant transmission and serological follow-up should be performed in high-risk newborns after vaccination to further lower the incidence of hepatitis B virus associated nephritis.</p>

An experimental study on the differentiation of bone marrow mesenchymal stem cells into vascular endothelial cells / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the feasibility of differentiation of bone marrow mesenchymal stem cells (MSCs) into vascular endothelial cells and the mechanism of its involvement in wound healing.</p><p><b>METHODS</b>Porcine MSCs were harvested from porcine marrow, and they were isolated and purified by density gradient centrifugation. After being cultured and amplified in vitro, the MSCs were labelled with BrdU (5-bromodeoxy-uridine). Full skin loss wound was created on the back of the mini-swine whose bone marrow was obtained. The labelled MSCs with fibrin glue as the vector were regrafted back to the donor animal wound. The wound tissue specimens were harvested at 2, 4, 6, 8 and 12 post-operation weeks and were immunohistochemically stained by BrdU and factor VIII (FVIII) for comparative study.</p><p><b>RESULTS</b>Most BrdU positive cells aggregated around small blood vessels in the granulation tissue of the wounds. Only individual vascular endothelial cells were BrdU positive. There was FVIII expression in the cytoplasm of BrdU positive cells.</p><p><b>CONCLUSION</b>MSCs were closely correlated with the formation of small blood vessels in granulation tissue during wound healing process. The porcine MSCs possessed the potential to differentiate into vascular entoehelial cells and to participate in wound healing under the micro-enviroment of the wound.</p>