Imaging surface structure and premelting of ice Ih with atomic resolution.

Ice surfaces are closely relevant to many physical and chemical properties, such as melting, freezing, friction, gas uptake and atmospheric reaction1-8. Despite extensive experimental and theoretical investigations9-17, the exact atomic structures of ice interfaces remain elusive owing to the vulnerable hydrogen-bonding network and the complicated premelting process. Here we realize atomic-resolution imaging of the basal (0001) surface structure of hexagonal water ice (ice Ih) by using qPlus-based cryogenic atomic force microscopy with a carbon monoxide-functionalized tip. We find that the crystalline ice-Ih surface consists of mixed Ih- and cubic (Ic)-stacking nanodomains, forming 19 × 19 periodic superstructures. Density functional theory reveals that this reconstructed surface is stabilized over the ideal ice surface mainly by minimizing the electrostatic repulsion between dangling OH bonds. Moreover, we observe that the ice surface gradually becomes disordered with increasing temperature (above 120 Kelvin), indicating the onset of the premelting process. The surface premelting occurs from the defective boundaries between the Ih and Ic domains and can be promoted by the formation of a planar local structure. These results put an end to the longstanding debate on ice surface structures and shed light on the molecular origin of ice premelting, which may lead to a paradigm shift in the understanding of ice physics and chemistry.

N-Acetyl-l-tryptophan inhibits CCl4-induced hepatic fibrogenesis via regulating TGF-ß1/SMAD and Hippo/YAP1 signal.

BACKGROUND: Although liver fibrosis is a key pathologic process in many liver diseases, therapeutic approaches for inhibiting liver fibrosis are still very limited. N-Acetyl-l-tryptophan (l-NAT) has a hepatoprotective effect via inhibiting the destruction of liver cells, enhancing cell viability and reducing the inflammation. However, the effect of l-NAT on liver fibrosis is not determined. PURPOSE: The present study investigated the effect of l-NAT on liver fibrosis and explored it potential molecular mechanism. METHODS: To address this concern, this study was carried out via fibrotic mice model induced by CCl4 and many approaches such as various histological staining methods, western blot assay, etc. RESULT: l-NAT decreased the levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) in fibrotic mice model induced by carbon tetrachloride (CCl4). Histological staining showed that l-NAT ameliorated liver injury and fibrosis, and reduced the expression of α-smooth muscle actin (α-SMA) and Collagen I protein. l-NAT also attenuated apoptosis by down-regulating the level of pro-apoptotic protein Bax and up-regulating that of anti-apoptotic protein Bcl-2. Moreover, l-NAT inhibited the expressions of TGF-ß1/SMAD and matrix metalloproteinase 9 (MMP9) proteins, and reversed the expression of YAP1 protein in CCl4-induced liver fibrosis. CONCLUSION: These results clearly demonstrated that l-NAT attenuated CCl4-induced liver fibrosis in mice, and this protective mechanism might relate to TGF-ß1/SMAD and Hippo/YAP1 signaling pathway. Thus, this study provided data basis for the prevention and treatment of liver fibrosis.

The Dietary Supplement γ-Oryzanol Attenuates Hepatic Ischemia Reperfusion Injury via Inhibiting Endoplasmic Reticulum Stress and HMGB1/NLRP3 Inflammasome.

The purpose of this study is to investigate the protective effect of γ-oryzanol (ORY) against hepatic ischemia reperfusion (HIR) injury and the potential protective mechanisms of ORY. ORY is an important biologically active ingredient isolated from rice bran oil, which has anti-inflammatory and antiapoptotic effects. However, it is still unknown whether ORY can protect the liver from the HIR damage. In this study, ORY was administered orally for seven days, after which the animals were subjected to liver ischemia for 60 minutes and reperfused for 6 hours. Related indicators were analyzed. The results showed that ORY pretreatment significantly reduced the levels of AST and ALT, relieved hepatocellular damage and apoptosis, and attenuated the exhaustion of SOD and GSH and accumulation of MDA and MPO. Interestingly, ORY treatment could significantly decreased ER stress. Furthermore, ORY pretreatment remarkably reduced the protein expressions of HMGB1, NLRP3, caspase-1 (p20), and IL-1ß to protect the liver from I/R-induced inflammasome activation and apoptosis. In conclusion, we demonstrated the potential effect of ORY in modulating oxidative stress, endoplasmic reticulum stress, and inflammasome activation during HIR.

Hic-5 deficiency protects cerulein-induced chronic pancreatitis via down-regulation of the NF-κB (p65)/IL-6 signalling pathway.

Chronic pancreatitis (CP), characterized by pancreatic fibrosis, is a recurrent, progressive and irreversible disease. Activation of the pancreatic stellate cells (PSCs) is considered a core event in pancreatic fibrosis. In this study, we investigated the role of hydrogen peroxide-inducible clone-5 (Hic-5) in CP. Analysis of the human pancreatic tissue samples revealed that Hic-5 was overexpressed in patients with CP and was extremely low in healthy pancreas. Hic-5 was significant up-regulated in the activated primary PSCs independently from transforming growth factor beta stimulation. CP induced by cerulein injection was ameliorated in Hic-5 knockout (KO) mice, as shown by staining of tissue level. Simultaneously, the activation ability of the primary PSCs from Hic-5 KO mice was significantly attenuated. We also found that the Hic-5 up-regulation by cerulein activated the NF-κB (p65)/IL-6 signalling pathway and regulated the downstream extracellular matrix (ECM) genes such as α-SMA and Col1a1. Therefore, we determined whether suppressing NF-κB/p65 alleviated CP by treating mice with the NF-κB/p65 inhibitor triptolide in the cerulein-induced CP model and found that pancreatic fibrosis was alleviated by NF-κB/p65 inhibition. These findings provide evidence for Hic-5 as a therapeutic target that plays a crucial role in regulating PSCs activation and pancreatic fibrosis.

Qingyi decoction attenuates severe acute pancreatitis in rats via inhibition of inflammation and protection of the intestinal barrier.

OBJECTIVE: Qingyi decoction (QYD) has beneficial effects in severe acute pancreatitis (SAP). We assessed the therapeutic effect and mechanisms of QYD in SAP. METHODS: A rat model of SAP was induced by pancreatic ductal injection of sodium taurocholate. QYD was administered intragastrically immediately postoperatively and once every 12 hours. Serum amylase, endotoxin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and D-lactate levels were measured at 12, 24, and 48 hours. Histological changes in the pancreas and ileum were analyzed. Expression of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-κB p65), Toll-like receptor 4 (TLR4), and zonula occludens-1 (ZO-1) in the small intestinal mucosa was also assessed. RESULTS: Pancreatic tissue showed extracellular space expansion, inflammatory infiltration, vessels with necrotic walls, and hemorrhage. Ileal tissue showed hemorrhage, inflammatory infiltration, and ileal mucosa destruction. These histological features were dramatically improved by QYD. Increased serum levels of amylase, endotoxin, TNF-α, IL-6, and D-lactic acid were significantly decreased by QYD administration. Increased expression of NF-κB p65 and TLR4 and decreased expression of ZO-1 in the ileal mucosa were also restored to normal levels by QYD treatment. CONCLUSION: QYD alleviates SAP by reducing intestinal barrier dysfunction, inhibiting intestinal bacteria and endotoxin translocation, and preventing NF-κB activation.