Liver fibrosis is characterized by the excessive deposition of extracellular matrix (ECM) in the hepatic parenchyma and represents an intrinsic response to chronic injury, maintaining organ integrity when extensive necrosis or apoptosis occurs. Hepatic stellate cells (HSCs) are the major cell type responsible for liver fibrosis. Following liver injury, HSCs become activated and transdifferentiate into myofibroblasts (MFBs) that lead to intrahepatic ECM accumulation. In the present study, we performed a meta‑analysis of datasets which included whole-genome transcriptional data on HSCs in the quiescent and activated state from two different rodent species and identified commonly regulated genes. Several of the genes identified, including ECM components, metalloproteinases and growth factors, were found to be well‑known markers for HSC activation. However, other significant genes also appeared to play important roles in hepatic fibrosis. The elucidation of the molecular events underlying HSC activation may be key to the identification of potential novel pharmacological targets for the prevention and treatment of liver fibrosis.

Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue tumor with intermediate malignancy. It is initially located on the skin from where it is able to infiltrate the deep structures and has a tendency to recur locally following inadequate excision. A t(17;22)(q22;q13) chromosome translocation is the main cytogenetic alteration responsible for the onset of DFSP. Treatment options include complete surgical excision by performing conventional surgery with wide margins (>3 cm) or Mohs micrographic surgery. A retrospective study was conducted in our Department of Plastic and Reconstructive Surgery and all data were collected from medical records of 59 DFSP patients within this department from 1999 to 2011. A total of 13 of 59 (22%) cases were treated with conventional excision; 3 (5%) cases resulted in tumor-free margins, 8 (14%) cases required surgical revision and 2 (3%) cases lead to recurrence. A total of 46 of 59 (78%) cases were treated with wide excision; 43 (73%) cases resulted in tumor-free margins, 3 (5%) cases required surgical revision and 0 (0%) cases lead to recurrence. In conclusion, the data collected reveal the controversy surrounding the adoption of general guidelines regarding safe margins. Further studies are required to investigate the possibility of obtaining genotypically altered margins from margins that may appear phenotypically healthy.

Background Previous studies have investigated facial artery perforators, but have reported inconsistent results regarding lateral nasal artery (LNA) perforators. Although several authors have described the use of LNA perforators for ala nasi and nasal sidewall reconstruction, the literature contains little information regarding the cadaveric dissection of LNA perforators, and most previously published studies have focused on facial artery perforators. Methods Sixteen hemifaces from eight fresh cadavers were dissected to study the LNA perforators. After the dissection was performed, the total length and diameter of the LNA and its perforators were measured. The quantity and the distribution of the LNA perforators supplying the overlying skin were then assessed. LNA perforator flaps were used for reconstruction in 10 nasal and perinasal defects. Results The mean total lengths of the LNA and its perforators were 49.37 mm and 16.06 mm, respectively. The mean diameters of the LNA and its perforators were 2.08 mm and 0.91 mm, respectively. Based on our findings, we mapped the face to indicate zones with a higher probability of finding perforators. No infection, hematoma, or complete flap necrosis were observed after the procedures. Conclusions Nasal reconstruction is a challenging procedure, and LNA propeller/V-Y perforator flaps are an excellent reconstructive option in certain cases. Based on our cadaveric study, we were able to identify an area in the upper third of the nasolabial groove with a high density of perforators.

HIV protease inhibitors (PIs) are antiretroviral agents, which have been found to also affect several cellular processes, such as inflammation and cell progression. In studies on non‐steroidal, anti‐inflammatory drugs, the addition of a nitric oxide (NO) moiety has been shown to both reduce their toxicity and enhance their pharmacological efficacy. Along this line of research, several derivatives of PIs have been synthesized by covalent attachment of NO moiety to the parental molecules. Previous work has indicated that NO‐hybridization of the prototypical PI, Saquinavir leads to a derivative named Saquinavir‐NO that while retaining the antiretroviral effect, acquires antitumoural and immunomodulatory properties along with reduced toxicity in vitro and in vivo. These data prompted us to evaluate the effects of NO‐hybridization on two other PIs, Lopinavir and Ritonavir. The two NO‐derivatives were compared head to head with their parental compounds on human primary peripheral blood mononuclear cells as well as on human primary macrophages. Lopinavir‐NO and Lopinavir were also screened in an in vivo model of autoimmune hepatitis. Our results prove that Lopinavir‐NO exerts markedly superior effects as compared to the parental compound both in vitro and in vivo. On the contrary, Ritonavir‐NO effects overlapped those of Ritonavir. These data demonstrate that NO‐hybridization of Lopinavir generates a derivative with significantly stronger immunomodulatory effects that are apparently related to an action of the compound on T‐cell secretory capacity. Lopinavir‐NO deserves additional studies for its possible use in T‐cell‐mediated autoimmune diseases including, but not limited to autoimmune hepatitis.