Biological scaffold-mediated delivery of myostatin inhibitor promotes a regenerative immune response in an animal model of Duchenne muscular dystrophy.

Recent studies have reported that the immune system significantly mediates skeletal muscle repair and regeneration. Additionally, biological scaffolds have been shown to play a role in polarizing the immune microenvironment toward pro-myogenic outcomes. Moreover, myostatin inhibitors are known to promote muscle regeneration and ameliorate fibrosis in animal models of Duchenne muscular dystrophy (DMD), a human disease characterized by chronic muscle degeneration. Biological scaffolds and myostatin inhibition can potentially influence immune-mediated regeneration in the dystrophic environment, but have not been evaluated together. Toward this end, here we created an injectable biological scaffold composed of hyaluronic acid and processed skeletal muscle extracellular matrix. This material formed a cytocompatible hydrogel at physiological temperatures in vitro When injected subfascially above the tibialis anterior muscles of both WT and dystrophic mdx-5Cv mice, a murine model of DMD, the hydrogel spreads across the entire muscle before completely degrading at 3 weeks in vivo We found that the hydrogel is associated with CD206+ pro-regenerative macrophage polarization and elevated anti-inflammatory cytokine expression in both WT and dystrophic mice. Co-injection of both hydrogel and myostatin inhibitor significantly increased FoxP3+ regulatory T cell modulation and Foxp3 gene expression in the scaffold immune microenvironment. Finally, delivery of myostatin inhibitor with the hydrogel increased its bioactivity in vivo, and transplantation of immortalized human myoblasts with the hydrogel promoted their survival in vivo This study identifies a key role for biological scaffolds and myostatin inhibitors in modulating a pro-regenerative immune microenvironment in dystrophic muscle.

Food insecurity during pregnancy and gestational weight gain.

BACKGROUND: Limited or uncertain availability of nutritionally adequate and safe food, known as food insecurity, has been associated with obesity and other adverse health outcomes, but has rarely been studied in pregnancy. Food insecurity may negatively affect behavioral and physiological changes during pregnancy and may be associated with poor perinatal outcomes including gestational weight gain. OBJECTIVE: Given the lack of information on the role of food insecurity in pregnancy and the possible relationship with perinatal outcomes such as gestational weight gain, the objective of this study was to examine the association between food insecurity and gestational weight gain in a diverse cohort of pregnant women. MATERIALS AND METHODS: This was an observational study of 299 English-speaking women who delivered live-born singleton gestations at ≥24 weeks at a single tertiary care center. During their postpartum hospitalizations, enrolled women completed a survey of food security status during pregnancy using the United States Department of Agriculture Household Food Security Survey Module. Scores were analyzed as inadequate (marginal, low, or very low) vs adequate (high) food security. Women without prepregnancy body mass index and gestational weight gain data were excluded. The primary outcome was gestational weight gain categorized as inadequate, adequate, or excessive based on 2009 National Academy of Medicine guidelines, which account for body mass index. Secondary outcomes included total gestational weight gain and other maternal and neonatal outcomes. Multivariable linear and multinomial logistic regressions were performed to assess the independent associations of food insecurity with gestational weight gain after controlling for potential confounding factors. RESULTS: Of the 299 women enrolled in the study, 11.0% (n = 33) reported inadequate food security during pregnancy. Women with inadequate food security were younger (P = .007), had a greater mean body mass index (P < .001), were more likely to be non-Hispanic black or Hispanic (P < .001) and publicly insured (P < .001), but were less likely to be employed (P < .001). Women with inadequate food security also had fewer prenatal visits (P < .001) and were less likely to have initiated prenatal care in the first trimester (P < .001). The occurrence of excessive gestational weight gain did not differ by food security status (33.3% inadequate food security vs. 43.6% adequate food security, an adjusted relative risk ratio of 0.42, 95% confidence interval 0.16 - 1.14). Median total gestational weight gain was lower for women with inadequate food security (9.2 kg, interquartile range 7.5 - 14.1) than for women with adequate food security (13.9 kg, interquartile range 10.6 - 16.7) (P < .001), and this difference persisted when controlling for potential confounders including prepregnancy body mass index (ß = -2.5, 95% confidence interval -5.0 to -0.21). CONCLUSIONS: In this diverse, urban population, more than 1 in 10 women experienced food insecurity during pregnancy. Inadequate food security was associated with lower median total gestational weight gain, but not with excessive gestational weight gain as determined by the 2009 National Academy of Medicine categories.