Subcutaneous Cavernous Haemangioma in a Patient with Klippel-Trenaunay Syndrome: A Case Report.

Background: Klippel-Trenaunay syndrome (KTS) is a rare congenital disease that mainly involves blood vessels and is characterized by the presence of capillary malformations (port wine stains), varicose veins, soft tissue and/or bone hypertrophy. Case Presentation: We report a 28-year-old man who was diagnosed 20 years ago with Klippel-Trenaunay syndrome. Approximately 3 years ago, he found enlarged masses on both upper extremities and a new dark red mass that was pathologically diagnosed as cavernous haemangioma appeared on the right index finger. Conclusion: KTS is a rare and potentially multisystem disease requiring multidisciplinary management for which imaging examination is an important auxiliary diagnostic method. Various complications may occur during its development, so regular follow-up is required to prevent serious accidents.

Ghrelin protects against ischemia/reperfusion-induced hepatic injury via inhibiting Caspase-11-mediated noncanonical pyroptosis.

BACKGROUND: Ischemia/reperfusion (I/R) injury is a complication of liver transplantation. I/R-induced inflammatory cell death, namely, pyroptosis, that is triggered by overactive inflammasomes results in the production of proinflammatory cytokines. Hepatic I/R injury correlates with the activation of the Caspase-11-mediated pyroptosis pathway. We investigated whether ghrelin, which is a pleiotropic gut hormone, may have anti-hepatic I/R injury effects, but the mechanism by which Ghrelin ameliorates hepatic I/R -induced injury remains a mystery. METHODS: Hepatic I/R injury was induced in a mouse model by clamping the left and right lobes of the liver for 90 min followed by reperfusion for 6 h, 12 h, or 24 h. As treatment, a saline with or without ghrelin was infused via the tail vain. Hepatocytes were isolated using a two-step collagenase liver perfusion method. RESULTS: In our study, treatment with ghrelin protected against hepatic I/R injury as shown by decreased alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels (p < 0.001) and reduced the histological injury in liver tissues compared with untreated controls. The LDH level of primary hepatocytes was increased by hypoxia/reoxygenation (H/R), and it was then restored to normal levels by ghrelin-treatment (p < 0.05). Western blotting analysis showed that ghrelin significantly inhibited the expression of pyroptosis-related proteins, including Caspase-11, GSDMD-N, NLRP3 and HMGB1, both in vivo and in vitro (all p < 0.05) compared with the untreated controls. Immunofluorescence showed that the expression of Gasdamin D (GSDMD) in hepatocytes was increased after I/R or H/R, whereas GSDMD expression was reduced by ghrelin treatment (p < 0.05). CONCLUSIONS: Our findings suggest that ghrelin ameliorated I/R-induced hepatic injury by inhibiting Caspase-11-mediated pyroptosis. Ghrelin may be a potential therapeutic option to prevent hepatic I/R injury after liver transplantation.

Ghrelin ameliorates transformation of hepatic ischemia-reperfusion injury to liver fibrosis by blocking Smad and ERK signalling pathways, and promoting anti-inflammation and anti-oxidation effects.

BACKGROUND & AIMS: Ghrelin, a gut hormone with pleiotropic effects, may act as a protective signal in parenchymal cells. Hepatic ischemia-reperfusion injury (HIRI) causes acute-on-chronic liver failure and induces transformation of acute to chronic injury. HIRI model of mice was established by a semi-hepatic blocking method and treated with Ghrelin. This process is involved in inflammation, oxidative stress damage and apoptosis, and is associated with the expansion and activation of fibrotic haematopoietic stem cells (HSCs) which express and secrete high levels of collagen that induces liver fibrosis. Therefore, we investigated the effects of Ghrelin during transformation of HIRI to liver fibrosis, and explored the molecular mechanism of Ghrelin's action based on Smad and ERK pathways. METHODS: Hepatic injury was detected by plasma ALT levels. The hepatic histology and collagen were elucidated by HE staining and Masson staining, respectively. Liver inflammation levels and inflammatory cell counts were assessed by MPO and HE staining, respectively. The antioxidant capacity of plasma was evaluated based on the levels of SOD, MDA, and XOD. The mRNA or protein expression levels of genes related to apoptosis, fibrosis, Smad, and ERK pathways were assessed by real-time quantitative PCR (RT-qPCR), ELISA, or western blotting. RESULTS: The HIRI model was established to investigate the effects of the liver injury transformed to liver fibrosis. Ghrelin exhibited good hepatic protection by ameliorating liver histological changes and decreasing plasma ALT levels. Ghrelin significantly decreased the expression of MPO than that in model group, suggesting that Ghrelin blocked the inflammatory response in the HIRI liver tissue; this supports the anti-inflammatory effects of Ghrelin. Ghrelin significantly decreased apoptosis (enhanced Bcl-2 expression, and down-regulated Bax and Caspase 3). Ghrelin exhibited anti-oxidative effects as it inhibited plasma MDA levels, and promoted plasma SOD and XOD levels. Moreover, Ghrelin inhibited activation of hepatic stellate cells, blocked traditional fibrotic Smad and ERK signalling pathways, and reduced hepatic fibrosis by stimulating degradation of extracellular matrices (ECMs; such as collagen I, collagen III, HA, and LN). CONCLUSIONS: This study demonstrates that Ghrelin delays the transformation of HIRI to liver fibrosis process which is correlated to its anti-apoptotic, anti-inflammatory, and anti-oxidative effects. Moreover, Ghrelin alleviates HIRI-mediated liver fibrosis, inhibits activation of HSCs, and reduces accumulation of ECM via inhibition of Smad and ERK signalling pathways.