Efficacy of Butyrate to Inhibit Colonic Cancer Cell Growth Is Cell Type-Specific and Apoptosis-Dependent.

Increasing dietary fiber consumption is linked to lower colon cancer incidence, and this anticancer effect is tied to elevated levels of short-chain fatty acids (e.g., butyrate) because of the fermentation of fiber by colonic bacteria. While butyrate inhibits cancer cell proliferation, the impact on cancer cell type remains largely unknown. To test the hypothesis that butyrate displays different inhibitory potentials due to cancer cell type, we determined half-maximal inhibitory concentrations (IC50) of butyrate in HCT116, HT-29, and Caco-2 human colon cancer cell proliferation at 24, 48, and 72 h. The IC50 (mM) butyrate concentrations of HCT116, HT-29, and Caco-2 cells were [24 h, 1.14; 48 h, 0.83; 72 h, 0.86], [24 h, N/D; 48 h, 2.42; 72 h, 2.15], and [24 h, N/D; 48 h, N/D; 72 h, 2.15], respectively. At the molecular level, phosphorylated ERK1/2 and c-Myc survival signals were decreased by (>30%) in HCT116, HT-29, and Caco-2 cells treated with 4 mM butyrate. Conversely, butyrate displayed a stronger potential (>1-fold) for inducing apoptosis and nuclear p21 tumor suppressor in HCT116 cells compared to HT-29 and Caco-2 cells. Moreover, survival analysis demonstrated that a cohort with high p21 gene expression in their colon tissue significantly increased survival time compared to a low-p21-expression cohort of colon cancer patients. Collectively, the inhibitory efficacy of butyrate is cell type-specific and apoptosis-dependent.

ZINC40099027 Promotes Gastric Mucosal Repair in Ongoing Aspirin-Associated Gastric Injury by Activating Focal Adhesion Kinase.

Nonsteroidal anti-inflammatory drugs cause gastric ulcers and gastritis. No drug that treats GI injury directly stimulates mucosal healing. ZINC40099027 (ZN27) activates focal adhesion kinase (FAK) and heals acute indomethacin-induced small bowel injury. We investigated the efficacy of ZN27 in rat and human gastric epithelial cells and ongoing aspirin-associated gastric injury. ZN27 (10 nM) stimulated FAK activation and wound closure in rat and human gastric cell lines. C57BL/6J mice were treated with 300 mg/kg/day aspirin for five days to induce ongoing gastric injury. One day after the initial injury, mice received 900 µg/kg/6 h ZN27, 10 mg/kg/day omeprazole, or 900 µg/kg/6 h ZN27 plus 10 mg/kg/day omeprazole. Like omeprazole, ZN27 reduced gastric injury vs. vehicle controls. ZN27-treated mice displayed better gastric architecture, with thicker mucosa and less hyperemia, inflammation, and submucosal edema, and lost less weight than vehicle controls. Gastric pH, serum creatinine, serum alanine aminotransferase (ALT), and renal and hepatic histology were unaffected by ZN27. Blinded scoring of pFAK-Y-397 immunoreactivity at the edge of ZN27-treated lesions demonstrated increased FAK activation, compared to vehicle-treated lesions, confirming target activation in vivo. These results suggest that ZN27 ameliorates ongoing aspirin-associated gastric mucosal injury by a pathway involving FAK activation. ZN27-derivatives may be useful to promote gastric mucosal repair.

An investigation into the effects of kinesiotaping for posture correction on kyphosis angle, pain, and balance in patients with postmenopausal osteoporosis-associated thoracic kyphosis.

Although positive effect of kinesiotaping in reducing back pain in addition to exercise was observed in 6-week follow-up, no additional contribution to exercise was demonstrated in kyphosis angle and balance assessment. Instantaneous positive effect of taping was observed in kyphosis angle and static balance measurement using a SportKAT device measurements 30 min after taping. OBJECTIVE: The present study aims to investigate whether kinesiotaping for posture correction in patients with osteoporosis-related increased kyphosis provides additional benefits to routine osteoporosis and balance exercises in reducing dorsal kyphosis angle, pain, and balance. METHOD: A single-center, parallel-group randomized controlled trial with unblinded assessments at baseline, week 3, and week 6 and additional measures 30 min immediately after taping in intervention group only. Forty-two female osteoporotic patients with hyperkyphosis were enrolled and randomized into 2 groups. The intervention group received an exercise program plus 3 sessions of kinesiotaping over the upper back; the control group received only an exercise program. The primary outcome measure was dorsal kyphosis angle, measured using a digital inclinometer. Secondary outcome measures were pain assessed on a visual analog scale (VAS 0-10 cm) and balance assessed with the Berg Balance Scale and SportKAT device. RESULTS: The study was conducted on 22 patients with an average age of 64 ± 7.08 in the control group and 20 patients with an average age of 63.1 ± 8.8 in the treatment group. There was not a significant difference when dorsal kyphosis angle of the two groups was compared in terms of the change between the baseline and week 6. The mean change in the control group was 0.86 ± 2 while it was 0.70 ± 1.75 in the intervention group. No significant difference was detected between the groups in terms of balance measurements. Significant differences were seen in favor of the intervention group when the VAS pain scores of the two groups were compared in terms of the change between the baseline and week 3 (p < 0.001) and the baseline and week 6 (p < 0.001), while no such difference was identified when the changes between weeks 3 and 6 were compared between the two groups. A significant effect on dorsal kyphosis angle and balance was also shown in the treatment group 30 min after taping. CONCLUSION: Application of kinesiotaping may have short-term positive effects on pain, but is unlikely to have significant effects on kyphosis angle or balance for women with osteoporosis. Positive changes seen in kyphosis angle and balance 30 min after taping are short-lived.

The relation between tooth loss and bone mass in postmenopausal osteoporotic women in Turkey: a multicenter study.

The purpose of this study was to investigate the associations of tooth loss with skeletal bone mass, years since menopause, educational level, current smoking status, dietary calcium intake, and number of pregnancies in postmenopausal osteoporotic women in Turkey. The study population consisted of 1171 postmenopausal women aged 40-86 years (mean age, 61.19 +/- 7.28 years). A detailed history was obtained from all women, including relevant lifestyle parameters, risk factors, and measurements of weight and height. Women were separated into three groups according to the number of teeth remaining as group 1 (edentulous, 457 women), group 2 (10 or fewer teeth, 232 women), and group 3 (more than 10 teeth remaining, 482 women). There was no significant difference among the three groups in mean age and menopausal age ( P < 0.05). Body mass index of group 1 was significantly higher than that of group 2 ( P< 0.01). Educational level was significantly different between three groups: groups 1 and 2 ( P< 0.001), groups 1 and 3 ( P< 0.0001), and groups 2 and 3 ( P< 0.001). Educational level was lowest in group 1 and highest in group 3. Despite a low ratio of cigarette smoking in general, a smoking habit was most prevalent in group 3 and least in group 2. The ratio of women receiving adequate calcium was significantly lower in group 1 than in other groups ( P< 0.001); mean calcium intake was similar in all groups. The number of pregnancies was significantly higher in group 1 than in other groups ( P< 0.001). Lumbar bone mineral density (BMD) of group 1 was significantly lower than that of groups 2 and 3 ( P< 0.001). Although no significant difference was found between groups 1 and 3, femoral neck BMD of group 2 was less than in others, and differences between groups 1 and 2 and between groups 2 and 3 ( P< 0.001) were significant. Lumbar bone mineral content (BMC) of group 1 was significantly lower than that of groups 2 and 3 ( P< 0.001), and lumbar BMC in group 2 was significantly higher than in group 3 ( P< 0.05). Femoral neck BMC in group 1 was significantly higher than in groups 2 and 3 ( P< 0.001). In conclusion, lumbar BMD and BMC in the edentulous group were significantly lower, whereas femoral neck BMD and BMC were significantly higher in edentulous group compared with the others. Our findings indicated that improvement in lifestyle factors and nutritional strategies for the treatment and prevention of osteoporosis may have additional benefit in reducing tooth loss.