Recent advances in hypertrophic scar

Hypertrophic scars (HTS) are predominant diseases after burn and trauma, which cause severe physiological and psychological problems. HTS have been researched for decades, and our knowledge about the mechanisms of HTS formation process has been increasing. However, the effects of currently available prevention and treatment strategies are limited. In this review, we summarize currently known mechanisms and recent studies of HTS, including extracellular matrix, matrix metalloproteinases, fibroblasts, myofibroblasts and their contraction ability, keratinocytes, growth factors, inflammatory and immune response, and stem cell treatment, hoping for a better understanding of HTS generation, development and effective translation to treatment strategies

Chemometric Classification and Geochemistry of Crude Oils in the Eastern Fukang Sag, Junggar Basin, NW China

Thirty oil samples collected from the eastern Fukang Sag were analyzed geochemically for their biomarkers and carbon isotopic compositions. The chemometric methods of principal component analysis and hierarchical cluster analysis, employed to thirteen parameters indicating source and depositional environment, classified the oil samples into three genetically distinct oil families: Family A oils were mainly derived from lower aquatic organisms deposited in a weakly reducing condition of fresh–brackish water, Family B oils came from a source containing predominantly terrigenous higher-plant organic matter laid down in an oxidizing environment of fresh water, and Family C oils received sources from both terrigenous and marine organic matter deposited in a weakly oxidizing to oxidizing environment of brackish water. Indirect oil–source correlations implied that Family A oils were probably derived from Permian source rocks, Family B oils originated mainly from Jurassic source rocks, and Family C oils had a mixed source of Carboniferous and Permian. Biomarker maturity parameters revealed that all three families of oils were in the mature stage. However, Family A oils were relatively less mature than Family B and Family C oils

Correction: Opposing Effects of PI3K/Akt and Smad-Dependent Signaling Pathways in NAG-1-Induced Glioblastoma Cell Apoptosis.

[This corrects the article DOI: 10.1371/journal.pone.0096283.]

Opposing effects of PI3K/Akt and Smad-dependent signaling pathways in NAG-1-induced glioblastoma cell apoptosis.

Nonsteroidal anti-inflammatory drug (NSAID) activated gene-1 (NAG-1) is a divergent member of the transforming growth factor-beta (TGF-β) superfamily. NAG-1 plays remarkable multifunctional roles in controlling diverse physiological and pathological processes including cancer. Like other TGF-β family members, NAG-1 can play dual roles during cancer development and progression by negatively or positively modulating cancer cell behaviors. In glioblastoma brain tumors, NAG-1 appears to act as a tumor suppressor gene; however, the precise underlying mechanisms have not been well elucidated. In the present study, we discovered that overexpression of NAG-1 induced apoptosis in U87 MG, U118 MG, U251 MG, and T98G cell lines via the intrinsic mitochondrial pathway, but not in A172 and LN-229 cell lines. NAG-1 could induce the phosphorylation of PI3K/Akt and Smad2/3 in all six tested glioblastoma cell lines, except Smad3 phosphorylation in A172 and LN-229 cell lines. In fact, Smad3 expression and its phosphorylation were almost undetectable in A172 and LN-229 cells. The PI3K inhibitors promoted NAG-1-induced glioblastoma cell apoptosis, while siRNAs to Smad2 and Smad3 decreased the apoptosis rate. NAG-1 also stimulated the direct interaction between Akt and Smad3 in glioblastoma cells. Elevating the level of Smad3 restored the sensitivity to NAG-1-induced apoptosis in A172 and LN-229 cells. In conclusion, our results suggest that PI3K/Akt and Smad-dependent signaling pathways display opposing effects in NAG-1-induced glioblastoma cell apoptosis

Acetylation-Dependent Regulation of Notch Signaling in Macrophages by SIRT1 Affects Sepsis Development

SIRT1 is reported to participate in macrophage differentiation and affect sepsis, and Notch signaling is widely reported to influence inflammation and macrophage activation. However, the specific mechanisms through which SIRT1 regulates sepsis and the relationship between SIRT1 and Notch signaling remain poorly elucidated. In this study, we found that SIRT1 levels were decreased in sepsis both in vitro and in vivo and that SIRT1 regulation of Notch signaling affected inflammation. In lipopolysaccharide (LPS)-induced sepsis, the levels of Notch signaling molecules, including Notch1, Notch2, Hes1, and intracellular domain of Notch (NICD), were increased. However, NICD could be deacetylated by SIRT1, and this led to the suppression of Notch signaling. Notably, in macrophages from myeloid-specific RBP-J−/− mice, in which Notch signaling is inhibited, pro-inflammatory cytokines were expressed at lower levels than in macrophages from wild-type littermates and in RBP-J−/− macrophages, and the NF-κB pathway was also inhibited. Accordingly, in the case of RBP-J−/− mice, LPS-induced inflammation and mortality were lower than in wild-type mice. Our results indicate that SIRT1 inhibits Notch signaling through NICD deacetylation and thus ultimately alleviates sepsis

NAG-1-induced apoptosis in a restricted set of glioblastoma cell lines.

<p>U87 MG, U118 MG, U251 MG, A172, LN-229, and T98G glioblastoma cell lines were infected by Ad-NAG-1 and Ad-Con at 50 MOI (multiplicity of infection), respectively. A, 24 h after infection, NAG-1 overexpression in cell lysates was verified by western blot. B, 24 h after infection, secreted NAG-1 in culture media was determined by ELISA. C, 48 h after infection, cell apoptosis was analyzed by FCM. 1, Ad-Con, 2, Ad-NAG-1. *, <i>P</i><0.05, **, <i>P</i><0.01 versus Ad-Con.</p

Involvement of PI3K/Akt and Smad2/3 in NAG-1-induced glioblastoma cell apoptosis.

<p>U87 MG, U118 MG, U251 MG, and T98G glioblastoma cell lines were infected by Ad-NAG-1 and Ad-Con at 50 MOI, respectively. A, at the same time of infection, 1 µM wortmannin or 10 µM LY294002 was added into the culture media. 24 h later, the Akt phosphorylation was analyzed by western blot. Smad2 or Smad3 siRNA was transfected into the cells. 24 h later, the interference effects were verified by western blot. B, C, the effect of wortmannin, LY294002, Smad2 siRNA, or Smad3 siRNA on Ad-Con or Ad-NAG-1-induced apoptosis was analyzed by FCM. 1, Ad-Con, 2, Ad-NAG-1. *, <i>P</i><0.05, **, <i>P</i><0.01 versus Ad-NAG-1.</p

NAG-1-activated signaling pathways in glioblastoma cells.

<p>U87 MG, U118 MG, U251 MG, A172, LN-229, and T98G glioblastoma cell lines were infected by Ad-NAG-1 and Ad-Con at 50 MOI, respectively. 24 h after infection, phosphorylation of PI3K(p85 Tyr458), Akt(Ser473), Smad2(Ser465/467), Smad3(Ser423/425), and ERK1/2(Thr202/Tyr204) was analyzed by western blot.</p

The direct interaction between Akt and Smad3 in NAG-1-overexpressed glioblastoma cells.

<p>A, U87 MG, U118 MG, U251 MG, and T98G glioblastoma cell lines were infected by Ad-NAG-1 and Ad-Con at 50 MOI, respectively. At the same time of infection, 1 µM wortmannin or 10 µM LY294002 was added into the culture media. 24 h later, the Smad3 phosphorylation was analyzed by western blot. B, U251 MG cells were infected by Ad-NAG-1 and Ad-Con at 50 MOI, respectively. 24 h later, the interaction of Akt and Smad3 was confirmed by co-immunoprecipitation. 1, Ad-Con, 2, Ad-NAG-1. Co-IP, co-immunoprecipitation. WB, western blot.</p