Proteoglycan 4 (PRG4) treatment enhances wound closure and tissue regeneration.

The wound healing response is one of most primitive and conserved physiological responses in the animal kingdom, as restoring tissue integrity/homeostasis can be the difference between life and death. Wound healing in mammals is mediated by immune cells and inflammatory signaling molecules that regulate tissue resident cells, including local progenitor cells, to mediate closure of the wound through formation of a scar. Proteoglycan 4 (PRG4), a protein found throughout the animal kingdom from fish to elephants, is best known as a glycoprotein that reduces friction between articulating surfaces (e.g. cartilage). Previously, PRG4 was also shown to regulate the inflammatory and fibrotic response. Based on this, we asked whether PRG4 plays a role in the wound healing response. Using an ear wound model, topical application of exogenous recombinant human (rh)PRG4 hastened wound closure and enhanced tissue regeneration. Our results also suggest that rhPRG4 may impact the fibrotic response, angiogenesis/blood flow to the injury site, macrophage inflammatory dynamics, recruitment of immune and increased proliferation of adult mesenchymal progenitor cells (MPCs) and promoting chondrogenic differentiation of MPCs to form the auricular cartilage scaffold of the injured ear. These results suggest that PRG4 has the potential to suppress scar formation while enhancing connective tissue regeneration post-injury by modulating aspects of each wound healing stage (blood clotting, inflammation, tissue generation and tissue remodeling). Therefore, we propose that rhPRG4 may represent a potential therapy to mitigate scar and improve wound healing.

Marijuana Use during Pregnancy and Lactation and Long-term Outcomes.

Recent surveys have shown increased use of marijuana during the perinatal period, possibly linked to increased legalization in many countries. Available information on the association between marijuana exposure and the effects on growth and development, as well as brain structure and function of the fetus, is growing but has not been uniform. Interpretation of these data is often challenging because of the influence of confounding factors and the sociodemographic variabilities in the study subjects. In this review, we present a synthesis of current information on the epidemiology and effects of marijuana use during pregnancy and evaluate the evidence for the immediate and long-term effects on affected neonates. We also describe the current knowledge and implications of breastfeeding and marijuana use and summarize selected current references about this practice. Finally, we provide the rationale for additional biological and population-based investigations to determine the various fetal outcomes of in-utero marijuana exposure that may assist in the establishment of prevention measures and applicable public health policies in the future.

Fetal Doppler Assessment in Neonatal Care: Analysis of Fetal Doppler Abnormalities and Neonatal Outcomes.

Fetal Doppler ultrasonography provides an effective and noninvasive approach to identify circulatory abnormalities in the maternal-fetal circulation. It is invaluable to assess the hemodynamic status of the fetus under a wide range of physiologic, infectious, and abnormal anatomic conditions. Findings from these studies are often used to make clinical decisions, including whether to proceed with urgent delivery of the fetus. In this review, we focus on key literature describing the main uses of Doppler ultrasonography in neonatal medicine, including how abnormal findings may be implicated in immediate and long-term outcomes. Our review highlights the importance of fetal Doppler examination as an effective intrauterine management strategy, and its full potential is more likely to be realized when considered in context with other available clinical information.

Sex Difference of Radiation Response in Occupational and Accidental Exposure.

Ionizing radiation is a well-established cause of deleterious effects on human health. Understanding the risks of radiation exposure is important for the development of protective measures and guidelines. Demographic factors such as age, sex, genetic susceptibility, comorbidities, and various other lifestyle factors influence the radiosensitivity of different subpopulations. Amongst these factors, the influence of sex differences on radiation sensitivity has been given very less attention. In fact, the International Commission on Radiological Protection (ICRP) has based its recommendations on a population average, rather than the data on the radiosensitivity of distinct subpopulations. In this study, we reviewed major human studies on the health risks of radiation exposure and showed that sex-related factors may potentially influence the long-term response to radiation exposure. Available data suggest that long-term radiosensitivity in women is higher than that in men who receive a comparable dose of radiation. The report on the biological effects of ionizing radiation (BEIR VII) published in 2006 by the National Academy of Sciences, United States emphasized that women may be at significantly greater risk of suffering and dying from radiation-induced cancer than men exposed to the same dose of radiation. We show that radiation effects are sex-specific, and long-term radiosensitivity in females is higher than that in males. We also discuss the radiation effects as a function of age. In the future, more systematic studies are needed to elucidate the sex differences in radiation responses across the life continuum - from preconception through childhood, adulthood, and old age - to ensure that boys and girls and men and women are equally protected across ages.

17-DMAG regulates p21 expression to induce chondrogenesis in vitro and in vivo.

Cartilage degeneration after injury affects a significant percentage of the population, including those that will go on to develop osteoarthritis (OA). Like humans, most mammals, including mice, are incapable of regenerating injured cartilage. Interestingly, it has previously been shown that p21 (Cdkn1a) knockout (p21-/-) mice demonstrate auricular (ear) cartilage regeneration. However, the loss of p21 expression is highly correlated with the development of numerous types of cancer and autoimmune diseases, limiting the therapeutic translation of these findings. Therefore, in this study, we employed a screening approach to identify an inhibitor (17-DMAG) that negatively regulates the expression of p21. We also validated that this compound can induce chondrogenesis in vitro (in adult mesenchymal stem cells) and in vivo (auricular cartilage injury model). Furthermore, our results suggest that 17-DMAG can induce the proliferation of terminally differentiated chondrocytes (in vitro and in vivo), while maintaining their chondrogenic phenotype. This study provides new insights into the regulation of chondrogenesis that might ultimately lead to new therapies for cartilage injury and/or OA.