NaHCO3 enhances the antitumor activities of cytokine-induced killer cells against hepatocellular carcinoma HepG2 cells.

The extracellular pH is lower inside solid tumors than in normal tissue. The acidic environment inhibits the cytotoxicity of lymphocytes in vitro and promotes tumor cell invasion. In the present study, both in vitro and in vivo experiments were conducted to investigate how NaHCO3 would affect the antitumor activities of cytokine-induced killer (CIK) cells against hepatocellular carcinoma (HCC) cells. For the in vitro experiments, HepG2 cells were cultured at pH 6.5 and 7.4 in the presence of CIK cells or CIK cell-conditioned medium (CMCIK). For the in vivo experiments, nude mice were xenografted with HepG2-luc cells and divided into four groups: i) CIK cells injection plus NaHCO3 feeding; ii) CIK cells injection plus drinking water feeding; iii) normal saline injection plus NaHCO3 feeding; and iv) normal saline injection plus drinking water feeding. The results indicated that the viability and growth rate of HepG2 cells were remarkably suppressed when co-cultured with CIK cells or CMCIK at pH 7.4 compared with those of HepG2 cells cultured under the same conditions but at pH 6.5. In the xenograft study, a marked synergistic antitumor effect of the combined therapy was observed. NaHCO3 feeding augmented the infiltration of cluster of differentiation 3-positive T lymphocytes into the tumor mass. Taken together, these data strongly suggest that the antitumor activities of CIK cells against HepG2 cells were negatively affected by the acidic environment inside the tumors, and neutralizing the pH (for example, via NaHCO3 administration), could therefore reduce or eliminate this influence. In addition, it should be recommended that oncologists routinely prescribe soda water to their patients, particularly during CIK cell therapy.

Intrabone marrow injection enhances placental mesenchymal stem cellmediated support of hematopoiesis in mice.

BACKGROUND/AIM: In order to determine the synergistic effects of human placental mesenchymal stem cells (PMSCs) on hematopoiesis in vivo, we compared the intrabone marrow injection (IBMI) with the conventional intravenous injection (IVI). MATERIALS AND METHODS: C57BL/6 recipient mice conditioned with lethal doses of irradiation were transplanted with bone marrow mononuclear cells (MNCs) and bone marrow-derived mesenchymal stem cells (BMSCs) from BALB/c mice by IBMI or IVI. NOD/SCID recipient mice conditioned with sublethal doses of irradiation were transplanted with human umbilical cord blood MNCs (UCB-MNCs) and PMSCs by IBMI or IVI. RESULTS: The number of hematopoietic cells was significantly higher in mice transplanted with BMSCs by IBMI than in those transplanted by IVI in a murine transplantation model (BALB/c→C57BL/6). Moreover, the percentage of human hematopoietic cells in the tibiae of the NOD/SCID mice that were transplanted with PMSCs plus UCB-MNCs was higher than that in mice transplanted with UCB-MNCs alone. In addition, in mice that were transplanted with PMSCs, PMSCs injected by IBMI were more efficient than those injected by IVI. CONCLUSION: Our results not only elucidated the role of PMSCs in promoting hematopoiesis, but also revealed the therapeutic potential of the combination of PMSCs and IBMI in transplantation.

[Developmental changes of acetabular cartilage complex: an experimental study of a straight-leg swaddle model of newborn rats].

OBJECTIVE: By establishing a model of straight-leg swaddle of newborn rats and observing the experimental animals'hips morphologically and pathologically, this study explored the changes of gross appearance of the acetabulum and the maturity of cartilage cells in the different regions of acetabular cartilage complex. METHODS: The legs and hips were fixed by adhesive tape for 10 days in the position of hip extension and adduction in 31 newborn Wistar rats (experimental group). The other 31 newborn rats without legs and hips treatment were used as the control group. After 10 days raising in the same condition, all the rats were sacrificed. The gross appearance, histological observations and VEGF and type X collagen immunohistochemistry were used for examining the acetabulum changes. RESULTS: A straight leg swaddle model of newborn rats was established successfully. In the experimental group the acetabulum became shallow and small and surrounded by more soft tissues. There were 49 dislocated hips (49/54) in the experimental group and 2 hips dislocated (2/60) in the control group (p<0.01). Fake acetabulum appeared in the experimental group. In the control group, the shape of the acetabulum was normol, and no fake acetabulum was found. The safranin O-fast green staining showed that the orange-red cartilage in the experimental group was wider than the control group. Immunohistochemistry observations showed VEGF and type X collagen immunoreactivities in the hypertrophic layer of the acetabular cartilage complex in the experimental group were lower than those in the control group. The percentages of VEGF positive and type X collagen positive cells in the iliac hypertrophic layer of the acetabular articular cartilage were significantly higher than those in the ischiadic ramus and the pubic branch in the experimental group. CONCLUSIONS: VEGF and type X collagen immunoreactivities in acetabular cartilage cells decrease in a straight-leg swaddle model of newborn rats. This suggests that this position might lead to dysmaturity of the acetabular cartilage cells and affect the development of the acetabulum.

Improving MCM-41 as a nitrosamines trap through a one-pot synthesis.

Copper oxide was incorporated into MCM-41 by a one-pot synthesis under acidic conditions to prepare a new mesoporous nitrosamines trap for protection of the environment. The resulting composites were characterized by XRD, N2 adsorption-desorption, and H2 temperature-programmed reduction techniques, and their adsorption capabilities were assessed in the gaseous adsorption of N-nitrosopyrrolidine (NPYR). The adsorption isotherms were consistent with the Freundlich equation. The copper salt was deposited onto MCM-41 during the evaporation stage and was fixed on the host in the calcination process that followed. MCM-41 was able to capture NPYR in air below 373 K but not at 453 K. Loading of copper oxide on MCM-41 greatly improved its adsorption capability at elevated temperatures. The influence of the incorporation of copper into MCM-41 samples and the adsorption behavior of these samples are discussed in detail.

Novel amorphous functional materials for trapping nitrosamines.

Novel amorphous functional materials are designed to modify amorphous silica with alumina. They are first presented as efficient adsorbents to trap both volatile nitrosamines and bulky tobacco specific nitrosamines in the environment. Selective adsorption, temperature programmed surface reaction (TPSR), and FTIR methods are employed to study the impact of alumina modification on the ability of silica to adsorb and catalytically degrade nitrosamines. Due to the special interaction between the N-NO group of nitrosamines and the aluminum ion in the composite, nitrosamines can be very easily trapped by the composite. Moreover, this cost-efficient material first shows a remarkable adsorptive capability and catalytic activity in reduction of NNN (N-nitrosonornicotine) in the liquid phase. The new concept of designing a multifunctional trap for carcinogenic pollutants, which combines the amorphous silica's pore structure with the specific adsorbing/catalyzing features of metal ions, proves feasible.

Adsorption of nitrosamines in acidic solution by zeolites.

Adsorption of N-nitrosopyrrolidine (NPYR) by zeolite NaZSM-5, Hbeta and NaZSM-11 in acidic solution with pH of 1 was investigated. The NPYR uptake process obeyed the first-rate Lagegren kinetic equation describing adsorption, and the equilibrium data were fitted to the Langmuir or Freundlich adsorption equation. Zeolite ZSM-5, Hbeta and NaZSM-11 possessed a higher adsorption capacity than amorphous silica or ordered mesoporous siliceous SBA-15, implying their potential application for adsorption of nitrosamines in gastric juice to anti-cancer.