Theracurmin inhibits intestinal polyp development in Apc‐mutant mice by inhibiting inflammation‐related factors

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Therefore, it is important to establish useful methods for preventing CRC. One prevention strategy involves the use of cancer chemopreventive agents, including functional foods. We focused on the well‐known cancer chemopreventive agent curcumin, which is derived from turmeric. However, curcumin has the disadvantage of being poorly soluble in water due to its high hydrophobicity. To overcome this problem, the formation of submicron particles with surface controlled technology has been applied to curcumin to give it remarkably improved water solubility, and this derived compound is named Theracurmin. To date, the preventive effects of Theracurmin on hereditary intestinal carcinogenesis have not been elucidated. Thus, we used Apc‐mutant mice, a model of familial adenomatous polyposis, to evaluate the effects of Theracurmin. First, we showed that treatment with 10‐20 µM Theracurmin for 24 hours reduced nuclear factor‐κB (NF‐κB) transcriptional activity in human colon cancer DLD‐1 and HCT116 cells. However, treatment with curcumin mixed in water did not change the NF‐κB promoter transcriptional activity. As NF‐κB is a regulator of inflammation‐related factors, we next investigated the downstream targets of NF‐κB: monocyte chemoattractant protein‐1 (MCP‐1) and interleukin (IL)‐6. We found that treatment with 500 ppm Theracurmin for 8 weeks inhibited intestinal polyp development and suppressed MCP‐1 and IL‐6 mRNA expression levels in the parts of the intestine with polyps. This report provides a proof of concept for the ongoing Theracurmin human trial (J‐CAP‐C study)

Effects of long-term cigarette smoke exposure on bone metabolism, structure, and quality in a mouse model of emphysema

Smoking is a common risk factor for both chronic obstructive pulmonary disease (COPD) and osteoporosis. In patients with COPD, severe emphysema is a risk factor for vertebral fracture; however, the effects of smoking or emphysema on bone health remain largely unknown. We report bone deterioration in a mouse model of emphysema induced by nose-only cigarette smoke (CS) exposure. Unexpectedly, short-term exposure for 4-weeks decreased bone turnover and increased bone volume in mice. However, prolonged exposure for 20- and 40-weeks reversed the effects from suppression to promotion of bone resorption. This long-term CS exposure increased osteoclast number and impaired bone growth, while it increased bone volume. Strikingly, long-term CS exposure deteriorated bone quality of the lumbar vertebrae as illustrated by disorientation of collagen fibers and the biological apatite c-axis. This animal model may provide a better understanding of the mechanisms underlying the deterioration of bone quality in pulmonary emphysema caused by smoking.Effects of long-term cigarette smoke exposure on bone metabolism, structure, and quality in a mouse model of emphysema. Mamoru Sasaki et al. PLOS ONE. 2018. 1(30) doi.org/10.1371/journal.pone.019161

Atherosclerotic plaque behind the stent changes after bare-metal and drug-eluting stent implantation in humans: Implications for late stent failure?

Background and aims The natural history and the role of atherosclerotic plaque located behind the stent (PBS) are still poorly understood. We evaluated the serial changes in PBS following bare-metal (BMS) compared to first-generation drug-eluting stent (DES) implantation and the impact of these changes on in-stent neointimal hyperplasia (NIH). Methods Three-dimensional coronary reconstruction by angiography and intravascular ultrasound was performed after intervention and at 6–10-month follow-up in 157 patients with 188 lesions treated with BMS (n = 89) and DES (n = 99). Results There was a significant decrease in PBS area (−7.2%; p  <  0.001) and vessel area (−1.7%; p  <  0.001) after BMS and a respective increase in both areas after DES implantation (6.1%; p  <  0.001 and 4.1%; p  <  0.001, respectively). The decrease in PBS area significantly predicted neointimal area at follow-up after BMS (β: 0.15; 95% confidence interval [CI]: 0.10–0.20, p  <  0.001) and DES (β: 0.09; 95% CI: 0.07–0.11; p  <  0.001) implantation. The decrease in PBS area was the most powerful predictor of significant NIH after BMS implantation (odds ratio: 1.13; 95% CI: 1.02–1.26; p = 0.02). Conclusions The decrease in PBS area after stent implantation is significantly associated with the magnitude of NIH development at follow-up. This finding raises the possibility of a communication between the lesion within the stent and the underlying native atherosclerotic plaque, and may have important implications regarding the pathobiology of in-stent restenosis and late/very late stent thrombosis

Temporary meniscus extrusion is caused by cumulative stress from uphill and downhill tasks in healthy volunteers

PurposeExcessive mechanical stress accumulates and causes knee injury. Meniscal extrusion is a key factor in detecting the reaction to cumulative mechanical stress. The accumulation of stress strongly depends on environmental conditions such as flat ground or uphill/downhill, and accumulates in knee compartments; only a few studies have reported the effects of different environments on lateral and medial meniscus extrusion. This study aimed to investigate the effects of cumulative uphill/downhill stress on the meniscal extrusion in each compartment.MethodsA total of 30 healthy volunteers with 30 affected knees were involved in this cohort study (mean age, 22.0 ± 1.1 years; men, n = 14). The participants were divided into flat-walking, uphill/downhill-walking, and uphill/downhill-jogging groups and their numbers of steps taken were recorded during the effort. Moreover, medial and lateral meniscal extrusions during walking were evaluated using ultrasound three times, before and after efforts (T1) and (T2), and one day after efforts (T3), respectively.ResultsIn the flat-walking group, no significant differences were observed between the follow-up periods. Conversely, in the uphill/downhill-walking and jogging groups, the medial meniscus extrusion at T2 was significantly higher than that at T1. Conversely, the medial meniscus extrusion at T3 was significantly lower than that at T2. By contrast, the lateral meniscus did not show any difference between the follow-up periods in any group.ConclusionTemporary extrusion of the meniscus occurred after uphill/downhill tasks in healthy volunteers, and its reaction was observed only in the medial meniscus

Arterial Remodeling and Endothelial Shear Stress Exhibit Significant Longitudinal Heterogeneity Along the Length of Coronary Plaques

Atherosclerosis is determined by both systemic risk factors and local vascular mechanisms. The arterial remodeling in response to plaque development plays a key role in atherosclerosis. Compensatory expansive remodeling is an adaptive mechanism that maintains lumen patency as a plaque develops. In contrast, excessive expansive remodeling, signifying an enlargement in vascular and lumen volume as a result of local plaque buildup, is a consistent attribute of high-risk plaques. Local hemodynamic factors, in particular low endothelial shear stress (ESS), is an intensely proinflammatory and proatherogenic stimulus and largely accounts for the spatially diverse distribution of atherosclerotic plaques. However, plaque, remodeling and ESS have hitherto been investigated only in the cross-sectional arterial axis and their distribution in the longitudinal axis of individual plaques has not been characterized

Search for Outer Massive Bodies around Transiting Planetary Systems: Candidates of Faint Stellar Companions around HAT-P-7

We present results of direct imaging observations for HAT-P-7 taken with the Subaru HiCIAO and the Calar Alto AstraLux. Since the close-in transiting planet HAT-P-7b was reported to have a highly tilted orbit, massive bodies such as giant planets, brown dwarfs, or a binary star are expected to exist in the outer region of this system. We show that there are indeed two candidates for distant faint stellar companions around HAT-P-7. We discuss possible roles played by such companions on the orbital evolution of HAT-P-7b. We conclude that as there is a third body in the system as reported by Winn et al. (2009, ApJL, 763, L99), the Kozai migration is less likely while planet-planet scattering is possible.Comment: 8 pages, 3 figures, 2 tables, PASJ in pres