Exploring the effects of formula feeding on infant immune development in China: A prospective cohort study.

BACKGROUND AND OBJECTIVES: The worldwide exclusive breastfeeding rate is suboptimal and this study aims to evaluate effects on infant immune development of formula feeding. METHODS AND STUDY DESIGN: A prospective study including 221 infants fed with breast milk or formula was conducted. At 3-month and 9-month, the concentrations of total immunoglobulin (Ig)G, IgM, IgA, IgG1, IgG2, interleukin (IL)-4, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) were measured by using enzyme-linked immunosorbent assay (ELISA). Natural killer (NK) cell activity and lymphocyte transformation testing were conducted. Furthermore, the occurrence of infantile diarrhea, respiratory infections and allergic diseases were questioned. RESULTS: The levels of total IgG (Z=-3.21, p=0.001), IgG1 (Z=-2.12, p=0.034), IFN-γ (t=-2.09, p=0.039) and NK cell activity (t=-2.14, p=0.034) were significant higher in formula-fed infants compared to breast-fed after 3 months. At 9-month, the levels of total IgG (Z=-4.34, p<0.001), IgA (Z=-2.05, p=0.041) and TNF-α (t=-2.10, p=0.037) of formula-fed infants were higher, but the lymphocyte stimulation index (t=2.76, p=0.007) was lower than breast-fed infants. While, no significant differences were found in the incidences of diarrhea and respiratory tract infection (p>0.05). CONCLUSIONS: This investigation suggested that formula- and breast-feeding have different contributions to infant immune development, but the formula feeding would not cause significantly increase of diarrhea and respiratory infections.

The lncRNA H19 promotes epithelial to mesenchymal transition by functioning as miRNA sponges in colorectal cancer.

Recently, the long non-coding RNA (lncRNA) H19 has been identified as an oncogenic gene in multiple cancer types and elevated expression of H19 was tightly linked to tumorigenesis and cancer progression. However, the molecular basis for this observation has not been characterized in colorectal cancer (CRC) especially during epithelial to mesenchymal transition (EMT) progression. In our studies, H19 was characterized as a novel regulator of EMT in CRC. We found that H19 was highly expressed in mesenchymal-like cancer cells and primary CRC tissues. Stable expression of H19 significantly promotes EMT progression and accelerates in vivo and in vitro tumor growth. Furthermore, by using bioinformatics study and RNA immunoprecipitation combined with luciferase reporter assays, we demonstrated that H19 functioned as a competing endogenous RNA (ceRNA) for miR-138 and miR-200a, antagonized their functions and led to the de-repression of their endogenous targets Vimentin, ZEB1, and ZEB2, all of which were core marker genes for mesenchymal cells. Taken together, these observations imply that the lncRNA H19 modulated the expression of multiple genes involved in EMT by acting as a competing endogenous RNA, which may build up the missing link between the regulatory miRNA network and EMT progression.

Identification of miRNAs that specifically target tumor suppressive KLF6-FL rather than oncogenic KLF6-SV1 isoform.

The Krüppel like factor 6 (KLF6) gene encodes multiple protein isoforms derived from alternative mRNA splicing, most of which are intimately involved in hepatocarcinogenesis and tumor progression. Recent bioinformatics analysis shows that alternative mRNA splicing of the KLF6 gene produces around 16 alternatively spliced variants with divergent or even opposing functions. Intriguingly, the full-length KLF6 (KLF6-FL) is a tumor suppressor gene frequently inactivated in liver cancer, whereas KLF6 splice variant 1 (KLF6-SV1) is an oncogenic isoform with antagonistic function against KLF6-FL. Compelling evidence indicates that miRNA, the small endogenous non-coding RNA (ncRNA), acts as a vital player in modulating a variety of cellular biological processes through targeting different mRNA regions of protein-coding genes. To identify the potential miRNAs specifically targeting KLF6-FL, we utilized bioinformatics analysis in combination with the luciferase reporter assays and screened out two miRNAs, namely miR-210 and miR-1301, specifically targeted the tumor suppressive KLF6-FL rather than the oncogenic KLF6-SV1. Our in vitro experiments demonstrated that stable expression of KLF6-FL inhibited cell proliferation, migration and angiogenesis while overexpression of miR-1301 promoted cell migration and angiogenesis. Further experiments demonstrated that miR-1301 was highly expressed in liver cancer cell lines as well as clinical specimens and we also identified the potential methylation and histone acetylation for miR-1301 gene. To sum up, our findings unveiled a novel molecular mechanism that specific miRNAs promoted tumorigenesis by targeting the tumor suppressive isoform KLF6-FL rather than its oncogenic isoform KLF6-SV1.

[Effect of autologous bone marrow stem cell transplantation on renal function following renal ischemic-reperfusion in rabbits].

OBJECTIVE: To observe the effect of autologous bone marrow stem cell (BMSC) transplantation via the renal artery on renal function recovery following renal ischemic-reperfusion (I/R) injury in rabbits. METHODS: BMSCs were collected and isolated from rabbits. Twenty-eight rabbits were subjected to renal pedicle clamping for 105 min and randomized subsequently into transplantation group and control group. BMSCs or saline were injected into the kidney via the renal artery, respectively. Before and 1, 3, 5, 7, 14, 21, and 28 days after I/R injury the venous blood was collected to measure the serum levels of SCr and BUN, and the renal tissue was sampled for pathological observation. RESULTS: One and 3 days after I/R injury, serum Cr and BUN levels increased significantly to the highest level in both groups. On the 7th day serum Cr and BUN levels in the transplantation group were lower than those in control group and remained so till the end of the experiment. On the 28th day, the levels of serum Cr (90.1+/-11.1 micromol/L) and BUN (8.0+/-1.5 mmol/L) in the transplantation group were significantly lower than those in the control group (135.6+/-32.5 micromol/L and 10.9+/-2.5 mmol/L, respectively, P<0.05). Pathological observation of the renal tissue revealed renal tubular epithelial cell degeneration, necrosis and abscission. CONCLUSION: BMSC transplantation can accelerate renal function repair after acute tubular necrosis resulting from I/R injury, and decrease serum Cr and BUN levels in early stage following the injury.