Dietary epicatechin improves survival and delays skeletal muscle degeneration in aged mice

We recently reported that epicatechin, a bioactive compound that occurs naturally in various common foods, promoted general health and survival of obese diabetic mice. It remains to be determined whether epicatechin extends health span and delays the process of aging. In the present study, epicatechin or its analogue epigallocatechin gallate (EGCG) (0.25% w/v in drinking water) was administered to 20-mo-old male C57BL mice fed a standard chow. The goal was to determine the antiaging effect. The results showed that supplementation with epicatechin for 37 wk strikingly increased the survival rate from 39 to 69%, whereas EGCG had no significant effect. Consistently, epicatechin improved physical activity, delayed degeneration of skeletal muscle (quadriceps), and shifted the profiles of the serum metabolites and skeletal muscle general mRNA expressions in aging mice toward the profiles observed in young mice. In particular, we found that dietary epicatechin significantly reversed age-altered mRNA and protein expressions of extracellular matrix and peroxisome proliferator–activated receptor pathways in skeletal muscle, and reversed the age-induced declines of the nicotinate and nicotinamide pathway both in serum and skeletal muscle. The present study provides evidence that epicatechin supplementation can exert an antiaging effect, including an increase in survival, an attenuation of the aging-related deterioration of skeletal muscles, and a protection against the aging-related decline in nicotinate and nicotinamide metabolism.—Si, H., Wang, X., Zhang, L., Parnell, L. D., Ahmed, B., LeRoith, T., Ansah, T.-A., Zhang, L., Li, J., Ordovás, J. M., Si, H., Liu, D., Lai, C.-Q. Dietary epicatechin improves survival and delays skeletal muscle degeneration in aged mice. FASEB J. 33, 965–977 (2019)

Matriks Jordan Dan Aplikasinya Pada Sistem Linier Waktu Diskrit

Matrix is diagonalizable (similar with matrix diagonal) if and only if the sum of geometric multiplicities of its eigenvalues is n.If we search for an upper triangular form that is nearly diagonal as possible but is still attainable by similarity for every matrix, especially the sum of geometric multiplicities of its eigenvalues is less than n, the result is the Jordan canonical form, which is denoted by , and . In this paper, will be described how to get matrix S(in order to get matrix ) by using generalized eigenvector. In addition, it will also describe the Jordan canonical form and its properties, and some observation and application on discrete time linear system

Combined Luteolin and Indole-3-Carbinol Synergistically Constrains ERα-Positive Breast Cancer by Dual Inhibiting Estrogen Receptor Alpha and Cyclin-Dependent Kinase 4/6 Pathway in Cultured Cells and Xenograft Mice

The high concentrations of individual phytochemicals in vitro studies cannot be physiologically achieved in humans. Our solution for this concentration gap between in vitro and human studies is to combine two or more phytochemicals. We screened 12 phytochemicals by pairwise combining two compounds at a low level to select combinations exerting the synergistic inhibitory effect of breast cancer cell proliferation. A novel combination of luteolin at 30 μM (LUT30) and indole-3-carbinol 40 μM (I3C40) identified that this combination (L30I40) synergistically constrains ERα+ breast cancer cell (MCF7 and T47D) proliferation only, but not triple-negative breast cancer cells. At the same time, the individual LUT30 and I3C40 do not have this anti-proliferative effect in ERα+ breast cancer cells. Moreover, this combination L30I40 does not have toxicity on endothelial cells compared to the current commercial drugs. Similarly, the combination of LUT and I3C (LUT10 mg + I3C10 mg/kg/day) (IP injection) synergistically suppresses tumor growth in MCF7 cells-derived xenograft mice, but the individual LUT (10 mg/kg/day) and I3C (20 mg/kg/day) do not show an inhibitory effect. This combination synergistically downregulates two major therapeutic targets ERα and cyclin dependent kinase (CDK) 4/6/retinoblastoma (Rb) pathway, both in cultured cells and xenograft tumors. These results provide a solid foundation that a combination of LUT and I3C may be a practical approach to treat ERα+ breast cancer cells after clinical trials

Combined Luteolin and Indole-3-Carbinol Synergistically Constrains ERα-Positive Breast Cancer by Dual Inhibiting Estrogen Receptor Alpha and Cyclin-Dependent Kinase 4/6 Pathway in Cultured Cells and Xenograft Mice

The high concentrations of individual phytochemicals in vitro studies cannot be physiologically achieved in humans. Our solution for this concentration gap between in vitro and human studies is to combine two or more phytochemicals. We screened 12 phytochemicals by pairwise combining two compounds at a low level to select combinations exerting the synergistic inhibitory effect of breast cancer cell proliferation. A novel combination of luteolin at 30 μM (LUT30) and indole-3-carbinol 40 μM (I3C40) identified that this combination (L30I40) synergistically constrains ERα+ breast cancer cell (MCF7 and T47D) proliferation only, but not triple-negative breast cancer cells. At the same time, the individual LUT30 and I3C40 do not have this anti-proliferative effect in ERα+ breast cancer cells. Moreover, this combination L30I40 does not have toxicity on endothelial cells compared to the current commercial drugs. Similarly, the combination of LUT and I3C (LUT10 mg + I3C10 mg/kg/day) (IP injection) synergistically suppresses tumor growth in MCF7 cells-derived xenograft mice, but the individual LUT (10 mg/kg/day) and I3C (20 mg/kg/day) do not show an inhibitory effect. This combination synergistically downregulates two major therapeutic targets ERα and cyclin dependent kinase (CDK) 4/6/retinoblastoma (Rb) pathway, both in cultured cells and xenograft tumors. These results provide a solid foundation that a combination of LUT and I3C may be a practical approach to treat ERα+ breast cancer cells after clinical trials

Design and Screening of New Lead Compounds for Autism Based on QSAR Model and Molecular Docking Studies

The purpose of the present study aims to develop a satisfactory model for predicting pro-social and pro-cognitive effects on azinesulfonamides of cyclic amine derivatives as potential antipsychotics. The three dimensional-quantitative structure affinity relationship (3D-QSAR) study was performed on a series of azinesulfonamides of cyclic amine derivative using comparative molecular similarity indices analysis (CoMSIA). The best statistical model of CoMSIA q2, r2, SEE and F values are 0.664, 0.973, 0.087, and 82.344, respectively. Based on the model contour maps and the highest activity structure of the 43rd compound, serial new structures were designed and the 43k1 compound was selected as the best structure. The dock results showed a good binding of 43k1 with the protein (PDB ID: 6A93). The QSAR model analysis of the contour maps can help us to provide guidelines for finding novel potential antipsychotics

Elevated Serum Levels of Retinol-Binding Protein 4 Are Associated with Breast Cancer Risk: A Case-Control Study

<div><p>Background</p><p>Retinol binding protein 4 (RBP4) is a recently identified adipokine that is elevated in patients with obesity or type 2 diabetes. A growing body of research has shown that RBP4 is associated with several types of cancer. However, no studies have investigated the relationship between serum RBP4 levels and breast cancer risk. We performed a case-control study to evaluate the association between serum RBP4 levels and the risk of breast cancer.</p><p>Methods</p><p>From August 2012 to December 2013, four-hundred subjects including 200 patients diagnosed with primary breast cancer and 200 matched healthy women were consecutively enrolled from Affiliated Hospital of Qingdao University Medical College. Blood samples were collected from healthy controls and breast cancer patients before commencement of treatment. Enzyme-linked immunosorbent assay was used to evaluate the serum RBP4 levels in separated serum samples. Meanwhile, the characteristics of breast cancer cases and controls were collected from medical records and pathological data.</p><p>Results</p><p>The serum levels of RBP4 were significantly higher in patients with breast cancer than that in the healthy control group (33.77±9.92 vs. 28.77±6.47μg/ml, P < 0.05). Compared to the subjects in the lowest quartile of serum RBP4 level, the adjusted ORs (95% CIs) is 2.16(1.01–4.61) and 2.07 (1.07–4.00) for women in the second and highest RBP4 tertile, respectively. For breast cancer patients, patients with PR or ER negative displayed significantly higher serum RBP4 levels than those with PR or ER positive.</p><p>Conclusion</p><p>Our results for the first time suggested serum RBP4 levels could be associated with the risk of breast cancer. However, further prospective studies are essential to confirm these observed results.</p></div

Logistic Regression Analysis of Risk of Breast cancer for Serum Levels of RBP4.

<p>Logistic Regression Analysis of Risk of Breast cancer for Serum Levels of RBP4.</p

Partial correlation coefficient (β) for RBP4 and metabolism indexes.

<p>Partial correlation coefficient (β) for RBP4 and metabolism indexes.</p

Stratified analyses of Odds ratios and 95% confidence intervals of breast cancer with RBP4.

<p>Stratified analyses of Odds ratios and 95% confidence intervals of breast cancer with RBP4.</p