Effect of MO-A on BBB disruption.

<p>(A) cell viability of OGD/R-induced bEnd.3 cell injury was determined with MTT assay; (B) Effect of MO-A on hypoxic BBB damage <i>in vitro</i>; Data are given as mean ± S.D. (n = 3); ^#<i>P</i> < 0.05 and ^##<i>P</i> < 0.01 <i>vs</i>. sham group by Student’s <i>t</i>-test statistical analysis; *<i>P</i> < 0.05 and **<i>P</i> < 0.01 <i>vs</i>. MCAO model group by one-way ANOVA statistical analysis.</p

Effects of MO-A on OGD/R-induced ROS generation in bEnd.3 cells.

<p>(A) DCF images indicate ROS generation in bEnd.3 cells; (B) graph represents quantification of fluorescence intensity in the images; Data are given as Mean ± S.D. (n = 6), ^#<i>P</i> < 0.05 and ^##<i>P</i> < 0.01 <i>vs</i>. sham group by Student’s <i>t</i>-test statistical analysis; *<i>P</i> < 0.05 and **<i>P</i> < 0.01 <i>vs</i>. MCAO model group by one-way ANOVA statistical analysis.</p

Methylophiopogonanone A Protects against Cerebral Ischemia/Reperfusion Injury and Attenuates Blood-Brain Barrier Disruption <i>In Vitro</i>

<div><p>Methylophiopogonanone A (MO-A), an active homoisoflavonoid of the Chinese herb <i>Ophiopogon japonicus</i> which has been shown to have protective effects on cerebral ischemia/reperfusion (I/R) injury, has been demonstrated to have anti-inflammatory and anti-oxidative properties. However, little is known about its role in cerebral I/R injury. Therefore, in this study, by using a middle cerebral artery occlusion (MCAO) and reperfusion rat model, the effect of MO-A on cerebral I/R injury was examined. The results showed that MO-A treatment reduced infarct volume and brain edema, improved neurological deficit scores, reversed animal body weight decreases, and increased animal survival time in the stroke groups. Western blotting showed that MO-A suppressed MMP-9, but restored the expression of claudin-3 and claudin-5. Furthermore, transmission electron microscopy were monitored to determine the blood–brain barrier (BBB) alterations <i>in vitro</i>. The results showed that MO-A markedly attenuated BBB damage <i>in vitro</i>. Additionally, MO-A inhibited ROS production in ECs and MMP-9 release in differentiated THP-1 cells <i>in vitro</i>, and suppressed ICAM-1 and VCAM-1 expression in ECs and leukocyte/EC adhesion. In conclusion, our data indicate that MO-A has therapeutic potential against cerebral I/R injury through its ability to attenuate BBB disruption by regulating the expression of MMP-9 and tight junction proteins.</p></div

Effect of MO-A on the expression of MMP-9 and tight junction proteins after MCAO in rats.

<p>(A) Representative blots of MMP-9 determined by Western blotting; (B) Quantitative analysis of the ratio of MMP-9; (C) Representative blots of claudin-3 and claudin-5 determined by Western blotting; (D) Quantitative analysis of the ratio of claudin-3 and claudin-5; Data are given as mean ± S.D. (n = 3); ^#<i>P</i> < 0.05 and ^##<i>P</i> < 0.01 <i>vs</i>. sham group by Student’s <i>t</i>-test statistical analysis; *<i>P</i> < 0.05 and **<i>P</i> < 0.01 <i>vs</i>. MCAO model group by one-way ANOVA statistical analysis.</p

Chemical structure of Methylophiopogonanone A (MO-A).

<p>Chemical structure of Methylophiopogonanone A (MO-A).</p

DataSheet_10_The causal relationship between sarcopenic obesity factors and benign prostate hyperplasia.csv

BackgroundBoth benign prostatic hyperplasia (BPH) and sarcopenic obesity (SO) are common conditions among older adult/adults males. The prevalent lifestyle associated with SO is a significant risk factor for the development of BPH. Therefore, we investigated the causal relationship between SO factors and BPH.MethodThe instrumental variables for SO factors were selected using the inverse variance-weighted method, which served as the primary approach for Mendelian randomization analysis to assess the causal effect based on summary data derived from genome-wide association studies of BPH.ResultThe increase in BMR (OR = 1.248; 95% CI = (1.087, 1.432); P = 0.002) and ALM (OR = 1.126; 95% CI = (1.032, 1.228); P = 0.008) was found to be associated with an elevated risk of BPH. However, no genetic causality between fat-free mass distribution, muscle mass distribution, and BPH was observed.ConclusionOur findings indicate that a genetic causal association between BMR, ALM and BPH. BMR and ALM are risk factors for BPH. The decrease in BMR and ALM signified the onset and progression of SO, thus SO is a protective factor for BPH.</p

MO-A protects against cerebral injury after MCAO in rats.

<p>(A) Infarct images using TTC staining at day 7 after MCAO; (B) Determination of infarct volume at day7 after MCAO (n: sham = 14, model = 9, MO-A 1.25mg/Kg group = 8, 2.50 mg/Kg group = 7, 5.00 mg/Kg group = 8); (C) Neurological deficit was evaluated using a five-point scale (n = 6–14); (D) The changes of animal body weights at day 3, 5 and 7, subtracted the body weights of day 1 (n = 6–14); (E) Animal survival times, rats were examined once every 3 hours at day 1 and once every 12 hours at day 2 to day 7 (n = 6–14). “Low mobility” and “animals incapable of feeding” were used as humane endpoints; (F) Determination of brain water contents in transient MCAO rats (n = 6–14); Data are given as mean ± S.D.; ^#<i>P</i> < 0.05 and ^##<i>P</i> < 0.01 <i>vs</i>. sham group by Student’s <i>t</i>-test statistical analysis; *<i>P</i> < 0.05 and **<i>P</i> < 0.01 <i>vs</i>. MCAO model group by Kruskal-Wallis H test in 7 day neurological deficit (C), weitht changes of 7 day (D) and water contents (F), and others by one-way ANOVA statistical analysis.</p

Direct effects of MO-A on the activation of endothelial cells and leukocytes.

<p>(A) Expression of ICAM-1 in OGD/R-induced bEnd.3 cells using ELISA, data are shown as Mean ± S.D. (n = 6); (B) Expression of VCAM-1 in OGD/R-induced bEnd.3 cells using ELISA, data are shown as Mean ± S.D. (n = 6); (C) Density of THP-1 cell adhesion to bEnd.3 following stimulation by TNF-α (10 ng/mL) or IL-1β (10 ng/ml), data are shown as Mean ± S.D. (n = 3); (D) MMP-9 secretion in undifferentiated and differentiated THP-1 cells stimulated by PMA (200 ng/mL) as detected by ELISA, data are shown as Mean ± S.D. (n = 6); ^#<i>P</i> < 0.05 and ^##<i>P</i> < 0.01 <i>vs</i>. sham group by Student’s <i>t</i>-test statistical analysis; *<i>P</i> < 0.05 and **<i>P</i> < 0.01 <i>vs</i>. MCAO model group by one-way ANOVA statistical analysis.</p