[In vivo osteogenic evaluation of titanium implants with strontium loaded nanotubes].

Objective: To evaluate the in vivo osteogenic activity of titanium implants with strontium loaded TiO2 nanotubes (NTSr). Methods: The strontium loaded titanium nanotubes were formed on pure titanium implants through anodization and hydrothermal treatment, and the unmodified titanium (Control) and sheer TiO2 nanotubes (NT) were set to be control groups and treatment group. Inductively coupled plasma mass spectrometry (ICP-MS) was used to evaluate the Sr release at 28 days. Field emission scanning electron microscopes (FE-SEM) was used to view the micro-topography, atomic force microscope was used to exam the surface roughness, and nano-indenter was used to evaluate the hardness of three groups (n=3). Three groups of implant samples were inserted into the distal femoral metaphysis of New Zealand rabbits (n=4 at each time point). After 4 weeks and 12 weeks, samples were harvested. Micro-CT scanning, immunofluorescent and histological examinations were carried out. Results: The strontium ions could be released slowly for at least 28 days [the Sr concentration at 28 Day was (2.6±1.5) ng/ml]. NTSr coating exhibited a nanoscale tube array (the diameter was about 70 nm), and the surface roughness of implant was increased with the nanobube coating [Control (34.8±5.3) nm, NT (66.2±4.3) nm, NTSr (85.7±10.6) nm, F=37.59, P<0.001]. The surface roughness (Ra) of NT and NTSr groups was higher than the control group (P<0.05). Comparing to Control implants, NTSr implants exhibited a better osteogenic ability [the bone volume/total volume (BV/TV) value was Control (24.7±1.1)% vs. NTSr (37.7±1.9)% at 4 weeks (P<0.05), and Control (40.7±0.9)% vs. NTSr (51.9±2.1)% at 12 weeks (P<0.05)]. The fluorescent examination revealed that NTSr coating can also accelerated the generation of new bone tissue (bone tissue area% labelled by alizarin red at day 7 was Control (19.2±2.9)% vs. NT (35.4±3.7)% vs. NTSr (40.9±0.9)% (F=42.74, P<0.01). The results in the NT and NTSr group were statistically higher than that in the control group (P<0.05). Conclusions: The strontium loaded TiO2 nanotubes can enhance new bone formation around titanium implants.

Effects of Artemisia Princeps Supplementation on Bone Metabolism in Ovariectomized Rats.

The aim of this study was to investigate the effects of Artemisia princeps (AP) extract on bone metabolism and its potential role in the prevention of osteoporosis in ovariectomized rats. Twenty-six female Sprague-Dawley rats were divided into five groups and treated as follows: sham-operated control group (SHAM); ovariectomized control group (OVX), ovariectomized group treated by gavage with 10 mg/kg/day alendronate (ALEN); ovariectomized group treated by gavage with 100 mg/kg/day Artemisia princeps (AP100); ovariectomized group treated by gavage with 300 mg/kg/day Artemisia princeps (AP300). Treatment of ovariectomized rats with AP extracts for 15 weeks prevented the reduction in bone thickness and trabecular bone mineral density caused by urinary Ca and Cr excretion, and also prevented the increase in bone turnover by maintaining the serum Ca/P ratio. As a result, the microarchitecture of the trabecular bone and cortical bone after ovariectomy was markedly improved by administration of AP extracts. In conclusion, AP prevented bone loss and osteoclast activity associated with high bone turnover in ovariectomized rats by controlling the serum Ca/P ratio and through anti-inflammatory and anti-oxidant properties. Our data implicate AP as a promising therapeutic option for the improvement of postmenopausal osteoporosis.

Identification of thiostrepton as a novel therapeutic agent that targets human colon cancer stem cells.

Accumulating evidence shows that colorectal cancer stem cells (CRSCs) are largely responsible for the metastasis and relapse of colorectal cancer (CRC) after therapy. Hence, identifying new agents that specifically target CRSCs would help improve the effectiveness of current CRC therapies. To accelerate identification of agents targeting CRSCs, the Connectivity Map (CMap) approach was used. Among the top-ranked candidates, thiostrepton, a thiazole antibiotic, was selected for further investigation because of its known tumoricidal activity. Thiostrepton could selectively induce apoptosis in CRSC subpopulations in both parental HCT-15 and HT-29 human CRC lines as well as in EMT and chemoresistant clones derived from them. Further, we investigated its inhibitory effects on the sphere- and colony-forming capabilities of the aforementioned CRC lines. The in vitro inhibition of sphere and colony formation was associated with downregulation of various modulators of the stem cell phenotype. The combination of thiostrepton and oxaliplatin eradicated both CD44(+) HCT-15 and HT-29 cells more efficiently than either drug alone. FoxM1, an oncogenic transcription factor, was identified as a critical positive modulator of stemness and as the main target of thiostrepton in the CRC lines. This is the first report showing the selective killing of CRSCs by thiostrepton, which has been proposed to be a promising anti-neoplastic agent. On the basis of its synergism with oxaliplatin in killing CRSCs in vitro, if this activity is confirmed in vivo, thiostrepton may be a promising agent to be used clinically in combination with current chemotherapies to improve the efficacy of these regimens.

In vivo growth suppression of CT-26 mouse colorectal cancer cells by adenovirus-expressed small hairpin RNA specifically targeting thymosin beta-4 mRNA.

Thymosin beta-4 (Tß4) is known to be involved in tumorigenesis. Overexpression of this polypeptide has been observed in a wide variety of cancers, including colorectal carcinoma (CRC). Accordingly, Tß4 has been proposed to be a novel therapeutic target for CRC, especially in its metastatic form. Although in vitro tumor-suppressive effects of Tß4 gene silencing mediated by small hairpin RNA (shRNA) have already been demonstrated, the in vivo efficacy of such an approach has not yet been reported. Herein, we demonstrated that infection with recombinant adenovirus expressing an shRNA targeting Tß4 markedly reduced the growth of and robustly induced apoptosis in CT-26 mouse CRC cells in culture. Additionally, tumors grown in nude mice from the CT-26 cells whose Tß4 expression already been downregulated by virus infection were also drastically reduced. Most importantly, significant growth arrest of tumors derived from the parental CT-26 cells was observed after multiple intratumoral injections of these viruses. Together, our results show for the first time that in vivo silencing of Tß4 expression by its shRNA generated after adenoviral infection can suppress CRC growth. These results further demonstrate the feasibility of treating CRC by a Tß4 knockdown gene therapeutic approach.

High intraocular pressure is associated with cardiometabolic risk factors in South Korean men: Korean National Health and Nutrition Examination Survey, 2008-2010.

OBJECTIVE: Elevated intraocular pressure (IOP) contributes to the progression of visual defects such as glaucoma. This study determined whether metabolic syndrome (MetS) and cardiovascular risk factors are associated with IOP in South Korean men. METHODS: We analyzed data on 4875 men who participated in the Korean National Health and Nutrition Examination Survey 2008-2010. We recorded the values for age, weight, height, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), insulin, homeostasis model assessment of estimated insulin resistance (HOMA-IR), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), non-HDL-C (NHDL-C), and TG/HDL-C, as well as sociodemographic factors. IOP was measured using Goldmann applanation tonometry. RESULTS: Weight, BMI, WC, SBP, DBP, FBG, insulin, HOMA-IR, TC, LDL-C, TG, NHDL-C, TG/HDL-C, and the prevalence of MetS differed significantly among the three groups with IOP (P<0.05). Mean IOP was higher in subjects who were obese and had hypertension, diabetes mellitus, MetS, abdominal obesity, high TG, high FBG, or high BP compared with normal subjects (P<0.005). Analysis using Pearson's correlation coefficient showed that all cardiometabolic risk factors were significantly associated with IOP (P<0.005), with the exception of WC and HDL-C. A multivariate linear regression analysis showed that IOP was positively correlated with BMI, SBP, DBP, FBG, HOMA-IR, TC, LDL-C, TG, NHDL-C, and TG/HDL-C after adjusting for all covariates (all P<0.05). CONCLUSIONS: Cardiometabolic risk factors, including the components of MetS, are associated with increased IOP.

Serum 25-hydroxyvitamin D levels and the risk of depression: a systematic review and meta-analysis.

OBJECTIVE: No quantitative systematic review or meta-analysis of population-based epidemiological studies has been conducted to assess the association between serum 25-hydroxyvitamin D (25(OH)D) levels and the risk of depression. This study aimed to summarize the current evidence from cross-sectional and prospective cohort studies that have evaluated the association between 25(OH)D levels and the risk of depression. METHODS: Relevant studies were identified by systematically searching the PubMed, EMBASE, Web of Science, and PsycINFO databases through April 2012. Cross-sectional and cohort studies that reported adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association of interest were included. The reported risk estimates for 25(OH)D categories were recalculated, employing a comprehensive trend estimation from summarized dose-response data. A pooled OR was calculated separately for cross-sectional and cohort studies using random-effects models. RESULTS: In the meta-analysis, 25(OH)D levels were significantly inversely associated with depression in 5 of 11 case-control studies and 2 of 5 cohort studies. The pooled estimate of the adjusted OR of depression in 11 cross-sectional studies (n = 43,137) was 0.96 (95% CI = 0.94-0.99, I2 = 63%) for a 10 ng/ml increase in 25(OH)D levels. The 5 included cohort studies comprised 12,648 participants, primarily elderly individuals, whose serum 25(OH)D levels were measured, and 2,663 experienced depression events during follow-up. The pooled adjusted OR of depression was 0.92 (95% CI = 0.87-0.98, I2 = 50%) for a 10 ng/ml increase in 25(OH)D levels. CONCLUSIONS: Our results indicate an inverse association between serum 25(OH)D levels and the risk of depression. Further studies are warranted to establish whether this association is causal.

Sleep duration and metabolic syndrome in adult populations: a meta-analysis of observational studies.

OBJECTIVE: Epidemiological studies have repeatedly investigated the association between sleep duration and metabolic syndrome. However, the results have been inconsistent. This meta-analysis aimed to summarize the current evidence from cross-sectional and prospective cohort studies that evaluated this. DATA SOURCES: Relevant studies were identified by systematically searching the PubMed, Cochrane CENTRAL, EMBASE and PsycINFO databases through November 2012 without language restriction. STUDY SELECTION: We identified 12 cross-sectional studies with 76 027 participants including 14 404 cases of metabolic syndrome, and 3 cohort studies with 2055 participants and 283 incident cases of metabolic syndrome. RESULTS: For short sleep durations (<5 to 6 h), the odds ratios (OR) was 1.27 (95% confidence interval (CI)=1.10-1.48, I(2)=75.5%) in the 12 cross-sectional studies and 1.62 (95% CI=0.74-3.55, I(2)=71.4%) in the 3 cohort studies; for long sleep durations (>8 to 10 h), the OR was 1.23 (95% CI=1.02-1.49, I(2)=75.8%) in the 11 cross-sectional studies and 1.62 (95% CI=0.86-3.04, I(2)=0.0%) in the 2 cohort studies. CONCLUSIONS: Short and long sleep durations are risky behaviors for increasing the risk of metabolic syndrome and thus have important public health implications, as sleep habits are amenable to behavioral interventions. The available data are sparse, and further studies, especially longitudinal studies, are needed to facilitate a better understanding of these associations.

MSC-DC interactions: MSC inhibit maturation and migration of BM-derived DC.

BACKGROUND: Mesenchymal stromal cells (MSC) comprise one of the BM stromal cells that are known to support hematopoiesis. It has also been suggested recently that MSC display immunosuppressive capacities through inhibiting the differentiation of monocyte-derived DC. DC travel to the lymph nodes (LN) to present Ag to T cells, and CCL21 is the chemokine that plays an important role in DC migration into the T-cell area of LN. We addressed the effect of MSC on this chemotactic activity of DC, one of the typical characteristics upon maturation. METHODS: BM cells were isolated and then cultured for generation of myeloid DC in the presence of GM-CSF and/or lipopolysaccharide with or without MSC. MSC were identified by flow cytometry of the immunologic markers and by performing colony-forming unit fibroblast assay. Migration of DC was observed with a newly developed time-lapse video microscopic technique. RESULTS: MSC co-culture inhibited the initial differentiation of DC, as well as their maturation. The matured DC actively migrated directionally in response to CCL21, a powerful DC-attracting chemokine, whereas the MSC co-cultured DC did not. DISCUSSION: Collectively, the findings of these experiments raise the possibility that MSC suppress the migratory function of DC and so they may serve immunoregulatory activities through the modulation of the Ag-presenting function of DC.

Cordyceps sinensis and its fractions stimulate MA-10 mouse Leydig tumor cell steroidogenesis.

The effects of Cordyceps sinensis (CS) and its extracted fractions on steroidogenesis in MA-10 cells were determined. Different concentrations of CS and 3 fractions of CS (F1, a water-soluble polysaccharide; F2, a water-soluble protein; and F3, a poorly water-soluble polysaccharide and protein) were added to MA-10 mouse Leydig tumor cells with or without human chorionic gonadotropin (hCG), and the production of steroid and the expression of steroidogenic acute regulatory protein (StAR) were examined. The results showed that CS alone (2-10 mg/mL) stimulated MA-10 cell progesterone production in a dose-dependent relationship. Fractions F1 and F3 (2-10 mg/mL) also had significant (P < .05) stimulatory effects on MA-10 cell steroidogenesis with a dose-dependent relationship. However, fraction F2 did not have an effect on MA-10 cells. CS and F3, but not F1, significantly induced more steroid production in hCG-stimulated MA-10 cells (P < .05). As a temporal relationship, F1 and F3 (2 mg/mL) maximally stimulated progesterone production between 1 and 3 hours after stimulation in MA-10 cells. In addition, CS and F3 significantly enhanced MA-10 cell StAR protein expression, which indicates that CS and F3 may use a cyclic adenosine monophosphate signal transduction pathway to activate MA-10 Leydig cell steroidogenesis in a manner to that of luteinizing hormone.