Effects of a group-mediated cognitive behavioral lifestyle intervention on select social cognitive outcomes in prostate cancer patients undergoing androgen deprivation therapy

Objective. To compare the effects of a group-mediated cognitive behavioral (GMCB) exercise and dietary (EX+D) intervention with those of standard-of-care (SC) treatment on select social cognitive outcomes in prostate cancer (PCa) patients undergoing androgen deprivation therapy (ADT). Methods. In the single-blind, 2-arm, randomized controlled Individualized Diet and Exercise Adherence–Pilot (IDEA-P) trial, 32 PCa patients (mean age = 66.2 years; SD = 7.8) undergoing ADT were randomly assigned to a 12-week EX+D intervention (n = 16) or SC treatment (n = 16). The exercise component of the personalized EX+D intervention integrated a combination of supervised resistance and aerobic exercise performed twice per week. The dietary component involved counseling and education to modify dietary intake and composition. Blinded assessments of social cognitive outcomes were obtained at baseline and 2-month and 3-month follow-up. Results. Intent-to-treat analysis of covariance demonstrated that the EX+D intervention resulted in significantly greater improvements in scheduling (P \u3c .05), coping (P \u3c .01), and exercise self-efficacy (P \u3c .05), and satisfaction with function (P \u3c .01) at 3 months relative to SC. Results of partial correlation analysis also demonstrated that select social cognitive outcomes were significantly correlated with primary trial outcomes of mobility performance and exercise participation (P \u3c .05) at 3-month follow-up. Conclusions: The GMCB lifestyle intervention yielded more favorable improvements in relevant social cognitive outcomes relative to SC among PCa patients undergoing ADT. Additionally, more favorable social cognitive outcomes were associated with superior mobility performance and exercise participation following the independent maintenance phase of the EX+D intervention

In vitro cell-autonomous myogenic differentiation of muscle SP cells and Lin- SP cells.

<p><b>A–C</b>: Phase pictures of wild type muscle SP cells cultured in EGM medium on Matrigel. Cells attached to Matrigel at days 3 (<b>A</b>), had significantly proliferated by day 7 (<b>B</b>), and differentiated into contracting multinucleated myotubes by day 11 (<b>C</b>). Scale bar  = 50 μm. <b>D–F</b>: Immunostaining of muscle SP cultures for the myotube marker α-actinin (<b>D</b>; green) at day 11; for the myoblast marker myogenin (<b>E</b>; green) at day 5; and for the satellite cell marker Pax 7 (F; green) at day 3. Cells were counterstained with DAPI (blue) to visualize nuclei. Scale bar  = 100 μm. <b>G</b>: Phase picture of day 11 cultures of primary myogenic cells in EGM medium on a Matrigel substrate showing formation of large numbers of myotubes. <b>H–I</b>: Isolation of muscle SP sub-populations by FACS. Total muscle mononuclear cells were labeled with antibodies to CD31 and CD45 and CD31+, CD45+ and Lin- cells were sorted first (<b>H</b>). Cells in each fraction were re-analyzed by FACS for incorporation of Hoechst and SP cells were isolated. The SP profile for the Lin- subset of cells in <b>H</b> is shown in <b>I</b>. MP cells are indicated. <b>J–L</b>: Phase pictures of day 11 cultures of CD45+ SP cells (<b>J</b>), CD31+ SP cells (<b>K</b>), and Lin- SP cells (<b>L</b>). Scale bar  = 50 μm. <b>M</b>: Pax7 mRNA was detected by RT-PCR in RNA isolated from muscle SP and Lin-SP cells but not CD31+/CD45− SP cells, Lin- MP cells shown in <b>I</b> were used as a positive control since they contain satellite cells. RNA was isolated immediately after cell isolation by FACS from wild type muscles.</p

In vitro lineage choices of Lin-SP cells isolated from wild type, mdx5cv, or cardiotoxin-injured muscle.

<p>Values represent mean ± standard deviation from 3 biological replicates.</p

CTX-injury and muscular dystrophy activate Lin- SP cells <i>in vivo</i> and alter their <i>in vitro</i> proliferation and morphology.

<p><b>A</b>: Histological comparison of tissue sections from wild type (WT), CTX-injured (CTX), and <i>mdx^5cv</i> (MDX) tibialis anterior muscle stained with Hematoxylin and Eosin. Wild type muscle shows closely apposed muscle fibers with peripherally located nuclei. CTX-injured muscle at 3 days post-injection has only a few degenerating myofibers surrounded by large numbers of mononuclear cells. Muscle from 8 week old <i>mdx^5cv</i> mice shows areas of active regeneration (white arrow), and areas of muscle degeneration with accumulations of inflammatory cells (green arrow). Scale bar  = 50 μm. <b>B</b>: Comparison of the number of Lin-SP cells isolated by FACS per gram of muscle from wild type, CTX-injured and <i>mdx^5cv</i> mice. Asterisks indicate a significant difference (p<0.01, Student's t-test) from wild type muscle. <b>C</b>: Quantification of <i>in vitro</i> Lin- SP cell proliferation using the Alamar Blue vital dye assay. Asterisks indicate a significant difference (p<0.001, linear regression analysis) from wild type muscle. <b>C</b>: Phase pictures of wild type, CTX and <i>mdx^5cv</i> Lin- SP cells at days 3, 8 and 11 in culture showing differences in cell adhesion, proliferation and morphology. Scale bar  = 50 μm.</p

Muscle damage abolishes <i>in vitro</i> myogenesis of Lin- SP cells and favors their differentiation into FAPs, fibroblasts and adipocytes.

<p>Cultures of Lin- SP cells isolated from wild type (WT) CTX-injured (CTX), or <i>mdx^5cv</i> mice were immunolabelled with antibodies to the myogenic (green) or mesenchymal (red) markers indicated. Labeling for Pax7 (satellite cells), PDGFRα (FAPs) and Collagen 1 (fibroblasts) was done on day 7 cultures. Labeling for α-actinin (myotubes) and C/ebpα (adipocytes) was performed at day 11. Scale bar for α-actinin pictures is 500 μm. Scale bar shown in WT Pax7 picture applies to all other pictures and is 100 μm.</p

Freshly isolated Lin-SP cells express FAPs surface markers but are capable of myogenic differentiation.

<p><b>A</b>: RT-PCR analysis of freshly isolated Lin- SP cells from wild type (WT) and <i>mdx^5cv</i> (MDX) muscle for myogenic markers (Pax7 and Myf5) and FAPs markers (PDGFRα and Sca1). Positive controls (PC) are sorted Sca1-positive cells for Sca1 and Lin- MP cells for Pax7, Myf5 and PDGFRα. Negative controls (NC) are sorted Sca1-negative cells for Sca1 and CD45-positive MP cells for Pax7, Myf5 and PDGFRα. <b>B, C</b>: FACS analysis of PDGFRα and Sca1 protein expression in Lin- SP cells (<b>B</b>) and Lin- MP cells (<b>C</b>) from wild type (WT) and <i>mdx^5cv</i> (MDX) muscle. Percentages of cells double positive (red) and double negative (green) for PDGFRα and Sca1 are shown. <b>D</b>: Confirmation by RT-PCR for PDGFRα expression in Lin- SP and Lin- MP cells sorted into PDGFRα-positive (Pα+) and PDGFRα-negative (Pα−) sub-fractions. <b>E</b>: <i>In vitro</i> myogenic differentiation of Lin- SP and MP cells sorted based on PDGFRα (Pα) expression. Cells were fixed after 14 days in culture and immunolabelled for α-actinin (green) to reveal myotubes. Cultures were counterstained with DAPI (blue) to visualize nuclei. Lin- MP Pα+ cells correspond to the previously characterized FAPs. Lin- MP Pα− cells are enriched in myogenic cells and also contain fibroblasts. Cultured wild type Lin- MP Pα− cells had 2,261 myotubes while cultured <i>mdx^5cv</i> Lin- MP Pα− cells had only 541 myotubes. Lin- SP Pα− cells did not survive in culture and are not shown. Scale bar  = 400 μm. <b>E</b>: Cultures of Lin- SP Pα− cells were double labeled with antibodies to α-actinin (green) and collagen I (red) to visualize myotubes and fibroblasts, respectively. Cultures of Lin- SP Pα− cells from dystrophic muscle (MDX) do not contain myotubes but give rise to fibroblasts. Scale bar  = 100 μm. <b>G</b>. Quantitative RT-PCR for Pax7 expression in Pdgfrα+ and Pdgfrα− Lin-SP cells, and Pdgfrα− Lin-MP cells. Data is presented as means +/− s.d. from 3 technical replicates.</p

Muscle SP cells express vascular endothelial cell markers and incorporate Acetylated-LDL in vivo.

<p>Values represent mean ± standard deviation from the indicated number (n) of biological replicates.</p

Intestinal Microbial Dysbiosis and Colonic Epithelial Cell Hyperproliferation by Dietary α-Mangostin is Independent of Mouse Strain

Beverages and supplements prepared from mangosteen fruit are claimed to support gut health and immunity, despite the absence of supporting evidence from clinical trials. We recently reported that α-mangostin (α-MG), the most abundant xanthone in mangosteen fruit, altered the intestinal microbiome, promoted dysbiosis, and exacerbated colitis in C57BL/6J mice. The objective of this study was to determine whether induction of dysbiosis by dietary α-MG is limited to the C57BL/6J strain or represents a more generic response to chronic intake of the xanthone on the gut microbiota of mice. C3H, Balb/c, Nude FoxN1nu, and C57BL/6J mice, each demonstrating unique microbiomes, were fed standard diet or diet containing 0.1% α-MG for four weeks. Dietary α-MG significantly altered the cecal and colonic microbiota in all four strains of mice, promoting a reduction in generally assumed beneficial bacterial groups while increasing the abundance of pathogenic bacteria. Consumption of α-MG was associated with reduced abundance of Firmicutes and increased abundance of Proteobacteria. The abundance of Lachnospiraceae, Ruminococcaceae, and Lactobacillaceae was reduced in α-MG-fed mice, while that of Enterobacteriaceae and Enterococcaceae was increased. Dietary α-MG also was associated with increased proliferation of colonic epithelial cells, infiltration of immune cells, infiltration of immune cells and increased fluid content in stool. These results suggest that ingestion of pharmacologic doses of xanthones in mangosteen-containing supplements may adversely alter the gut microbiota and should be used with caution