Tuning osteoporotic macrophage responses to favour regeneration by Cu-bearing titanium alloy in Porphyromonas gingivalis lipopolysaccharide-induced microenvironments

Guided bone regeneration in inflammatory microenvironments of osteoporotic patients with large alveolar bone defects remains a great challenge. Macrophages are necessary for alveolar bone regeneration via their polarization and paracrine actions. Our previous studies showed that Cu-bearing Ti6Al4V alloys are capable of regulating macrophage responses. When considering the complexity of oral microenvironments, the influences of Cu-bearing Ti6Al4V alloys on osteoporotic macrophages in infectious microenvironments are worthy of further investigations. In this study, we fabricated Ti6Al4V-Cu alloy by selective laser melting technology and used Porphyromonas gingivalis lipopolysaccharide (P.g-LPS) to imitate oral pathogenic bacterial infections. Then, we evaluated the impacts of Ti6Al4V-Cu on osteoporotic macrophages in infectious microenvironments. Our results indicated that Ti6Al4V-Cu not only inhibited the P.g-LPS-induced M1 polarization and pro-inflammatory cytokine production of osteoporotic macrophages but also shifted polarization towards the pro-regenerative M2 phenotype and remarkably promoted anti-inflammatory cytokine release. In addition, Ti6Al4V-Cu effectively promoted the activity of COMMD1 to potentially repress NF-κB-mediated transcription. It is concluded that the Cu-bearing Ti6Al4V alloy results in ameliorated osteoporotic macrophage responses to create a favourable microenvironment under infectious conditions, which holds promise to develop a GBR-barrier membrane for alveolar bone regeneration of osteoporosis patients.

Unveiling the potential of purinergic signaling in schistosomiasis treatment

: Schistosomiasis is a neglected tropical disease. It is related to long-lasting granulomatous fibrosis and inflammation of target organs, and current sub-optimal pharmacological treatment awakens global public health concerns. Intravascular worms and eggs release antigens and extracellular vesicles that target host endothelial cells, modulate the immune system, and stimulate the release of damage-associated molecular patterns (DAMPs). ATP, one of the most studied DAMP, triggers a cascade of autocrine and paracrine actions through purinergic P2X and P2Y receptors, which are shaped by ectonucleotidases (CD39). Both P2 receptor families, and in particular P2Y1, P2Y2, P2Y12, and P2X7 receptors, have been attracting increasing interest in several inflammatory diseases and drug development. Current data obtained in the murine model unveil a CD39-ADP-P2Y1/P2Y12 receptors signaling pathway linked to liver and mesenteric exacerbations of schistosomal inflammation. Therefore, we propose that members of this purinergic signaling could be putative pharmacological targets to reduce schistosomal morbidity.

Ovarian Insulin-Like Growth Factor-I

The insulin-like growth factor-I is a pleotropic growth factor that modulates cell replication. Insulin-like growth factor-I is produced by granulosa, theca and luteal cells and have autocrine and paracrine actions. It plays a crucial role in animal fertility acting as a monitoring signal. Researches have shown that synergistically with gonadotropins it stimulates the growth, survivability and steroidogenesis of follicular cells.

Promotion of Hair Growth by Conditioned Medium from Extracellular Matrix/Stromal Vascular Fraction Gel in C57BL/6 Mice

Adipose-derived stem cell- (ADSC-) based regenerative medicine has expanded to include the treatment of hair loss. However, stem cell therapy remains a relatively recent technique, and reports of its use for treating alopecia are rare. ADSCs exert biological functions via the paracrine actions of various growth factors and cytokines. Conditioned medium from ADSCs (ADSCs-CM) is a cell-free suspension rich in growth factors and cytokines that has demonstrated a significant role in stimulating hair growth, with encouraging outcomes in terms of hair regeneration and hair growth. Extracellular matrix/stromal vascular fraction gel (ECM/SVF-gel) is an ADSC- and adipose native extracellular matrix-enriched product for cytotherapy. In this study, we compared the effects of CM from ECM/SVF-gel (ECM/SVF-CM) and from stem cells (SVF-CM) on hair growth in mice. ECM/SVF-CM stimulated hair growth more than SVF-CM, through promoting the proliferation of dermal papilla cells and cells in the bulge, neovascularization, and anagen induction. ECM/SVF-CM might, thus, provide an effective and improved strategy for promoting hair growth. These data provide a theoretical foundation for the clinical administration of ECM/SVF-CM for the treatment of hair loss.

Betatrophin knockdown induces beiging and mitochondria biogenesis of white adipocytes

Remodeling of energy-storing white fat into energy-consuming beige fat has led to a promising new approach to alleviate adiposity. Several studies have shown adipokines can induce white adipose tissue (WAT) beiging through autocrine or paracrine actions. Betatrophin, a novel adipokine, has been linked to energy expenditure and lipolysis but not clearly clarified. Here, we using high-fat diet-induced obesity to determine how betatrophin modulate beiging and adiposity. We found that betatrophin-knockdown mice displayed less white fat mass and decreased plasma TG and NEFA levels. Consistently, inhibition of betatrophin leads to the phenotype change of adipocytes characterized by increased mitochondria contents, beige adipocytes and mitochondria biogenesis-specific markers both in vivo and in vitro. Of note, blocking AMP-activated protein kinase (AMPK) signaling pathway is able to abolish enhanced beige-like characteristics in betatrophin-knockdown adipocytes. Collectively, downregulation of betatrophin induces beiging in white adipocytes through activation of AMPK signaling pathway. These processes suggest betatrophin as a latent therapeutic target for obesity.