[Clinical significance and mechanism of TBX5 gene in colorectal cancer].

Objective: To examine the expression of T-box5 (TBX5) in colorectal cancer tissues and its clinical significance, and explore the effects of TBX5 on the invasion and metastasis of colorectal cancer cells and its mechanism. Methods: The expressions of TBX5 in cancer and adjacent normal tissues were tested by immunohistochemistry (IHC), and the relationship between TBX5 and clinicopathological features and prognosis of colorectal cancer was analyzed. Real-time quantitative PCR (RT-qPCR) and western blot were used to detect the expressions of TBX5 in different colorectal cancer cell lines. TBX5 overexpression plasmid was constructed and transfected into human colorectal cancer cell line HT-29, and cell counting kit-8 (CCK-8) was used to detect the activities of transfection HT-29 cells. Cell scratch test and Transwell assay were used to detect the migration and invasion abilities of cells, while RT-qPCR and western blot were used to detect the mRNA and protein expressions of PCNA, p21, p16, p27, MMP-2, MMP-7 and TIMP-1. Results: The positive rate of TBX5 protein in colorectal cancer tissues was 24.44% (22/90), significantly lower than 65.56% of adjacent normal tissues (P<0.001). The expression of TBX5 was significantly related to lymph node metastasis, depth of invasion and nerve invasion (P<0.05). The survival period of 22 patients with positive TBX5 expression was (60.2±2.4) months, better than (44.3±2.8) months of 68 patients with negative TBX5 expression (P<0.05). Among human colon cancer cell lines of HT29, SW620, SW480, LOVO and HCT116, the expression of TBX5 in HT29 cells was the weakest. After transfection, the expression of TBX5 in transfection group was significantly higher than those in control group and blank group (P=0.043 and P<0.001). Cell viability in transfection group was significantly lower than those in control group and blank group (both P<0.001). The ratio of cells in G(0)/G(1) phase was increased (P=0.009), while in G(2)/M phase was decreased (P<0.001). Cells' abilities of migration and invasion in transfection group were also significantly decreased (both P<0.001). Overexpression of TBX5 downregulated the expressions of PCNA, MMP-2 and MMP-7, while upregulated the expressions of p21, p16, p27 (P<0.05 for all). TBX5 had marginal effect on the expression of TIMP-1 (P>0.05). Conclusions: Downregulation of TBX5 is a marker of poor prognosis in patients with colorectal cancer. TBX5 may inhibit the progression of colorectal cancer by inhibiting proliferation, invasion and metastasis related genes.

Vitamin D supplementation for osteoporosis in older adults: can we make it help better?

With the increase of the average age of our population, the incidence of diseases specific for older adults has been increasing. One of such diseases is osteoporosis. The true incidence of osteoporosis is unknown. But the estimates indicate that this disease affects wide proportions of the population, ranging in millions or even ten millions in large countries like the United States. As this poses a significant burden on the health care system, interventions that could prevent or treat this condition are in the focus of clinical research. Vitamin D, the determinant of bone health, has been tested in clinical studies as the agent to treat osteoporosis. Despite the progress, there is still some controversy about the targeted blood levels of vitamin D, most efficient way to supplement this vitamin, and clinical efficacy of this supplementation in the elderly.In the present review, we will highlight the metabolism of vitamin D and the aforementioned unresolved issues, as well as review the recent interventional studies on vitamin D supplementation. In the present review, we will highlight the metabolism of vitamin D and the aforementioned unresolved issues, as well as review the recent interventional studies on vitamin D supplementation.

Enhanced effects of low molecular weight heparin intercalated with layered double hydroxide nanoparticles on rat vascular smooth muscle cells.

Surgical procedures to remove atherosclerotic lesions and restore blood flow also injure the artery wall, promoting vascular smooth muscle cell (SMC) phenotypic change, migration, proliferation, matrix production and ultimately, restenosis of the artery. Hence identification of effective anti-restenotic strategies is a high priority in cardiovascular research, and SMCs are a key target for intervention. This paper presents the in vitro study of layered double hydroxides (LDHs) as drug delivery system for an anti-restenotic drug (low molecular weight heparin, LMWH). The cytotoxicity tests showed that LDH itself had very limited toxicity at concentrations below 50 microg/mL over 6-day incubation. LDH nanoparticles loaded with LMWH (LMWH-LDHs) were prepared and tested on rat vascular SMCs. When conjugated to LDH particles, LMWH enhanced its ability to inhibit SMC proliferation and migration, with greater than above 60% reduction compared with the control (growth medium) over 3 or 7-day incubation. Cellular uptake studies showed that compared with LMWH alone, LMWH-LDH hybrids were internalized by SMCs more rapidly, and uptake was sustained over a longer time, possibly revealing the mechanisms underlying the enhanced biological function of LMWH-LDH. The results suggest the potential of LMWH-LDH as an efficient anti-restenotic drug for clinical application.

Efficient siRNA delivery to mammalian cells using layered double hydroxide nanoparticles.

Although siRNAs have surpassed expectations in experiments to alter gene expression in vitro, the lack of an efficient in vivo delivery system still remains a challenge in siRNA therapeutics development and has been recognized as a major hurdle for clinical applications. In this paper we describe an inorganic nanoparticle-based delivery system that is readily adaptable for in vivo systems. Layered double hydroxide (LDH) nanoparticles, a family of inorganic crystals, tightly bind, protect, and release siRNA molecules and deliver them efficiently to mammalian cells in vitro. The uptake of siRNA-loaded LDH nanoparticles occurs via endocytosis, whereby the nanoparticles dissolve due to the low pH in the endosome, thereby aiding endosomal escape into the cytoplasm. The influence of LDH nanoparticles on cell viability and proliferation is negligible at concentrations