[Show abstract][Hide abstract] ABSTRACT: Pancreatitis induced by hypertriglyceridemia (HTG) has gained much attention. However, very limited numbers of studies have focused on the clinical significance of TG elevation in non-HTG induced pancreatitis, such as acute biliary pancreatitis (ABP). This study aimed to study the clinical significances of triglyceride (TG) elevation in patients with ABP.
We retrospectively analyzed a total of 426 ABP cases in our research center. According to the highest TG level within 72 h of disease onset, the patients were divided into a normal TG group and an elevated TG group. We analyzed the differences between the two groups of patients in aspects such as general information, disease severity, APACHE II (acute physiology and chronic health evaluation II) and Ranson scores, inflammatory cytokines, complications and prognosis.
Compared with the normal TG group, patients in the elevated TG group showed a significantly higher body mass index and were significantly younger. TG elevation at the early stage of ABP was associated with higher risk of severe pancreatitis and organ failures, especially respiratory failure. For patients with severe pancreatitis, those with elevated TG levels were more likely to have a larger area of necrosis, and higher incidence of pancreatic abscess as well as higher mortality (17.78% versus 9.80%, P < 0.05).
In ABP patients, TG elevation might participate in the aggravation of pancreatitis and the occurrence of systemic or local complications. Thus, the TG level may serve as an important indicator to determine the prognosis of patients with ABP.
[Show abstract][Hide abstract] ABSTRACT: Four and a half LIM protein 1 (FHL1) has been characterized as a tumor suppressor in various types of tumor. However, the biological function and underlying mechanism of FHL1 in tongue squamous cell carcinoma (TSCC) remain to be elucidated. The present study demonstrated that FHL1 inhibits anchorage‑dependent and ‑independent growth of TSCC cells in vitro and tumor growth in nude mice, as determined by cell proliferation and soft agar assays. Knockdown of FHL1 with FHL1 small interfering RNA (siRNA) promoted tumor growth in nude mice. Mechanistically, flow cytometric analysis showed that knockdown of FHL1 promoted G1/S cell cycle progression. Furthermore, expression of cell cycle‑associated regulators, cyclin D and cyclin E, were detected by western blotting and reverse transcription‑quantitative polymerase chain reaction. Cyclin D and cyclin E were markedly elevated at both the protein and mRNA level in the FHL1 siRNA‑transfected cells. These results suggested that FHL1 has a tumor suppressive role in TSCC and that FHL1 may be a useful target for TSCC gene therapy.
Molecular Medicine Reports 05/2015; 12(3). DOI:10.3892/mmr.2015.3844 · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
This study aimed to investigate the therapeutic potential of hydrogen-rich saline on pancreatic ischemia/reperfusion (I/R) injury in rats.
Eighty heterotopic pancreas transplantations (HPT) were performed in syngenic rats. The receptors were randomized blindly into the following three groups: the HPT group and two groups that underwent transplantation and administration of hydrogen-rich saline (HS, >0.6 mM, 6 mL/kg) or normal saline (NS, 6 mL/kg) via the tail vein at the beginning of reperfusion (HPT + HS group, HPT + NS group). Samples from the pancreas and blood were taken at 12 hours after reperfusion. The protective effects of hydrogen-rich saline against I/R injury were evaluated by determining the changes in histopathology and measuring serological parameters, oxidative stress-associated molecules, and proinflammatory cytokines.
Administration of hydrogen-rich saline produced notable protection against pancreatic I/R injury in rats. Histopathological improvements and recovery of impaired pancreatic function were observed. In addition, TNF-α, IL-1β, and IL-6 were reduced markedly in the HPT + HS group. Additionally, there were noticeable inhibitory effects on the pancreatic malondialdehyde level and considerable recruitment of SOD and GPx, which are antioxidants.
Hydrogen-rich saline treatment significantly attenuated the severity of pancreatic I/R injury in rats, possibly by reducing oxidative stress and inflammation.
Mediators of Inflammation 04/2015; 2015:281985. DOI:10.1155/2015/281985 · 3.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: High mobility group box 1 (HMGB1) plays important roles in a large variety of diseases; glycyrrhizin (GL) is recognized as an HMGB1 inhibitor. However, few studies have focused on whether glycyrrhizin can potentially improve the outcome of traumatic pancreatitis (TP) by inhibiting HMGB1.
A total of 60 male Wistar rats were randomly divided into three groups (n = 20 in each): Control group, TP group and TP-GL group. Pancreatic trauma was established with a custom-made biological impact machine-III, and GL was administered at 15 minutes after the accomplishment of operation. To determine survival rates during the first 7 days after injury, another 60 rats (n = 20 in each) were grouped and treated as mentioned above. At 24 hours of induction of TP, the histopathological changes in pancreas were evaluated and serum amylase levels were tested. Serum tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and HMGB1 were measured using enzyme linked immunosorbent assay. HMGB1 expressions in pancreas were measured using immunohistochemical staining, Western blot and Real-Time PCR analysis.
Serum levels of HMGB1, TNF-α and IL-6 were increased dramatically in TP group at 24 hours after induction of TP. However, these indicators were reduced significantly by GL administration in TP-GL group comparing with TP group (P<0.05). Meanwhile, survival analysis showed that the seven-day survival rate in TP-GL group was significantly higher than that in TP group (85% versus 65%, P<0.05). GL treatment significantly decreased the pancreatic protein and mRNA expressions of HMGB1 and ameliorated the pancreatic injury in rats with TP.
Glycyrrhizin might play an important role in improving survival rates and ameliorating pancreatic injury of TP by suppression of the expressions of HMGB1 and other proinflammatory cytokine.
PLoS ONE 12/2014; 9(12):e115982. DOI:10.1371/journal.pone.0115982 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Proximity to functional substrates may enhance the coupling between the quantum degrees of
freedom and thus develop nontrivial quantum effects in graphene. Here, we demonstrate the
successful fabrication of graphene in proximity to atomically flat magnetic insulating LaMnO3
films. The insulating nature of the LaMnO3 films not only ensures the electronic transport only
occur in the graphene layers but also allow them to serve as dielectric layers for gating. Transport
measurements reveal anomalous behaviors, including asymmetrical longitudinal magnetoresistivity
and nonlinear Hall effect. This work may pave a way toward the realization of intriguing quantum
phases in graphene.
[Show abstract][Hide abstract] ABSTRACT: FHL1 is an important tumor-suppressor that is downregulated in multiple tumors by unknown mechanisms. We demonstrated that miR-410 specifically targets the 3'UTR of FHL1. Furthermore, using DNA bisulfite modification and sequencing experiments, we demonstrated that the FHL1 promoter is hypermethylated in cancer cells. FHL1 methylation is increased upon miR-410 expression, suggesting that the regulation of FHL1 by miR-410 occurs by a dual mechanism. Using chromatin immunoprecipitation assays, we observed that miR-410 overexpression results in the increased binding of DNMT3A at the FHL1 promoter, which could explain how miR-410 regulates FHL1 methylation. Importantly, in vitro and in vivo results suggest that miR-410 may have oncogenic properties. Furthermore, both miR-410 and DNMT3A are upregulated in clinical human liver and colorectal tumors cancers. Our results suggest that miR-410 may function as an oncomiR and are consistent with its key function in regulating FHL1 in certain digestive system cancers.
PLoS ONE 10/2014; 9(10):e108708. DOI:10.1371/journal.pone.0108708 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The activator protein-1 (AP-1) transcription factor complex plays a crucial role in tumor growth and progression. However, how AP-1 transcriptional activity is repressed is not fully understood. Here, we show that RNA-binding protein with multiple splicing 1 (RBPMS1) physically and functionally interacts with AP-1 in vitro and in vivo. The RNA-recognition motif (RRM) and C-terminus of the RBPMS1 isoforms RBPMS1A and RBPMS1C, but not RBPMS1B, interacted with cFos, a member of the AP-1 family that dimerizes with cJun to stimulate AP-1 transcriptional activity. RBPMS1 did not associate with Jun proteins. RBPMS1A and RBPMS1C bound to the basic leucine zipper (bZIP) domain of cFos that mediates dimerization of AP-1 proteins. In addition, RBPMS1A-C interacted with the transcription factor Smad3, which was shown to interact with cJun and increase AP-1 transcriptional activity. RBPMS1 inhibited c-Fos or Smad3-mediated AP-1 transactivation and the expression of AP-1 target genes known to be the key regulators of cancer growth and progression, including vascular endothelial growth factor (VEGF) and cyclin D1. Mechanistically, RBPMS1 blocks the formation of the cFos/cJun or Smad3/cJun complex as well as the recruitment of cFos or Smad3 to the promoters of AP-1 target genes. In cultured cells and a mouse xenograft model, RBPMS1 inhibited the growth and migration of breast cancer cells through c-Fos or Smad3. These data suggest that RBPMS1 is a critical repressor of AP-1 signaling and RBPMS1 activation may be a useful strategy for cancer treatment.
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 09/2014; 1853(1):1-13. DOI:10.1016/j.bbamcr.2014.09.022 · 5.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Exchange bias effect is observed in the phase separated La0.33Pr0.34Ca0.33MnO3 thin films. High exchange bias field of about 1 kOe is achieved at 4 K. The exchange bias effect in La0.33Pr0.34Ca0.33MnO3 thin films might originate from the intrinsic phase separation of the La0.33Pr0.34Ca0.33MnO3 or surface effect. The dependence of exchange bias effect on temperature, cooling field, and thickness is also investigated. This work would open an avenue to the application in the magnetic memory devices based on the phase separated manganites.
Chinese journal of chemical physics 08/2014; 27(4):475-478. DOI:10.1063/1674-0068/27/04/475-478 · 0.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lattice distortion due to oxygen octahedral rotations have a significant role in mediating the magnetism in oxides, and recently attracts a lot of interests in the study of complex oxides interface. However, the direct experimental evidence for the interrelation between octahedral rotation and magnetism at interface is scarce. Here we demonstrate that interfacial octahedral rotation are closely linked to the strongly modified ferromagnetism in (LaMnO3+δ)N/(SrTiO3)N superlattices. The maximized ferromagnetic moment in the N=6 superlattice is accompanied by a metastable structure (space group Imcm) featuring minimal octahedral rotations (a(-)a(-)c(-), α~4.2°, γ~0.5°). Quenched ferromagnetism for N<4 superlattices is correlated to a substantially enhanced c axis octahedral rotation (a(-)a(-)c(-), α~3.8°, γ~8° for N=2). Monte-Carlo simulation based on double-exchange model qualitatively reproduces the experimental observation, confirming the correlation between octahedral rotation and magnetism. Our study demonstrates that engineering superlattices with controllable interfacial structures can be a feasible new route in realizing functional magnetic materials.
[Show abstract][Hide abstract] ABSTRACT: Estrogen receptors ERα and ERβ share considerable sequence homology yet exert opposite effects on breast cancer cell proliferation. While the proliferative role of ERα in breast tumors is well characterized, it is not clear whether the antitumor activity of ERβ can be mobilized in breast cancer cells. Here, we have shown that phosphorylation of a tyrosine residue (Y36) present in ERβ, but not in ERα, dictates ERβ-specific activation of transcription and is required for ERβ-dependent inhibition of cancer cell growth in culture and in murine xenografts. Additionally, the c-ABL tyrosine kinase and EYA2 phosphatase directly and diametrically controlled the phosphorylation status of Y36 and subsequent ERβ function. A nonphosphorylatable, transcriptionally active ERβ mutant retained antitumor activity but circumvented control by upstream regulators. Phosphorylation of Y36 was required for ERβ-mediated coactivator recruitment to ERβ target promoters. In human breast cancer samples, elevated phosphorylation of Y36 in ERβ correlated with high levels of c-ABL but low EYA2 levels. Furthermore, compared with total ERβ, the presence of phosphorylated Y36-specific ERβ was strongly associated with both disease-free and overall survival in patients with stage II and III disease. Together, these data identify a signaling circuitry that regulates ERβ-specific antitumor activity and has potential as both a prognostic tool and a molecular target for cancer therapy.
[Show abstract][Hide abstract] ABSTRACT: A novel optical gating method is demonstrated to achieve controllable ambipolar tuning of graphene on diverse semiconductor substrates. Furthermore, electronic fabrication to form erasable electronic superlattices in structurally homogenous graphene is proposed based on selective optical gating. The created p-p(+) superlattices exhibits counterintuitive transport properties, which can be attributed to nonlinear effects in the carrier dynamics around the interfaces.
[Show abstract][Hide abstract] ABSTRACT: Eye absent (Eya) proteins are involved in cell fate determination in a broad spectrum of cells and tissues. Aberrant expression of Eya2 has been documented in a variety of cancers and correlates with clinical outcome. However, whether microRNAs (miRNAs) can regulate Eya2 expression remains unknown. Here, we show that miR-30a represses Eya2 expression by binding to the 3’-untranslated region of Eya2. Overexpression of Eya2 in miR-30a-transfected breast cancer cells effectively rescued the inhibition of cell proliferation and migration caused by miR-30a. Knockdown of Eya2 by small-interfering RNA (siRNA) in breast cancer cells mimicked the effect induced by miR-30a and abolished the ability of miR-30a to regulate breast cancer cell proliferation and migration. The miR-30a/Eya2 axis could regulate G1/S cell cycle progression, accompanied by the modulation of expression of cell cycle-related proteins, including cyclin A, cyclin D1, cyclin E, and c-Myc. Moreover, miR-30a expression was downregulated in breast cancer patients, and negatively correlated with Eya2, which was upregulated in breast cancer patients. These data suggest that the miR-30a/Eya2 axis may play an important role in breast cancer development and progression and that miR-30a activation or Eya2 inhibition may be a useful strategy for cancer treatment.
Biochemical and Biophysical Research Communications 03/2014; 445(2). DOI:10.1016/j.bbrc.2014.01.174 · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Huge intrinsic tunnel magnetoresistance effects at low field are demonstrated in macroscopic La0.33Pr0.34Ca0.33MnO3 thin films etched with periodic antidot arrays, and a highest magnetoresistance ratio (about 1600%) is achieved at 58 K. Such giant tunnel magnetoresistance effect might originate from delicate phase separation and coherent transport under the applied periodic spatial confinement. Strong transport fluctuation is also revealed in such systems due to phase competition. Our findings pave a way to realize tunnel magnetoresistance devices based on electronically phase separated materials with spatial modulations.
[Show abstract][Hide abstract] ABSTRACT: Annular pancreas (AP) concurrent with pancreaticobiliary maljunction (PBMJ), an unusual coexisted congenital anomaly, often presented symptoms and subjected surgical treatment at the early age of life. We reported the first adult case of concurrent AP with PBMJ presented with symptoms until his twenties, and performed a literature review to analyze the clinicopathological features of such cases comparing with its pediatric counterpart.
The main clinical features of this case were abdominal pain and increased levels of plasma amylase as well as liver function test. A complete type of annular pancreas with duodenal stenosis was found, and dilated common bile duct with high confluence of pancreaticobiliary ducts was also observed. Meanwhile, extremely high levels of bile amylase were detected both in common bile duct and gallbladder. The patient received duodenojejunostomy (side-to-side anastomosis) as well as choledochojejunostomy (Roux-en-Y anastomosis), adnd was discharged in a good condition.
AP concurrent with PBMJ usually presents as duodenal obstruction in infancy, while manifests as pancreatitis in adulthood. Careful long-term follow-up is required for children with AP considering its association with PBMJ which would induce various intractable pathologic conditions in the biliary tract and pancreas.
[Show abstract][Hide abstract] ABSTRACT: Increasing evidence has demonstrated that toll like receptor 4 (TLR4) mediated systemic inflammatory response syndrome (SIRS) accompanied with multiple organ failure, is one of the most common causes of death in patients with severe acute pancreatitis (SAP). Recent reports have revealed that heparan sulfate (HS) proteoglycan, a component of extracellular matrices potentiates the activation of intracellular proinflammatory responses via TLR4, contributing to the aggravation of acute pancreatitis (AP). However, little is known about the participants in the HS/TLR4 mediated inflammatory cascades. Our previous work provided a clue that a membrane potassium channel (MaxiK) is responsible for HS-induced production of inflammatory cytokines. Therefore, in this report we attempted to reveal the roles of MaxiK in the activation of macrophages stimulated by HS. Our results showed that incubation of RAW264.7 cells with HS upregulated MaxiK and TLR4 expression levels. HS could also activate MaxiK channel to promote the efflux of potassium ion from cells, as measured by the elevated activity of caspase-1, whereas it was significantly abolished by the treatment with paxilline, a specific blocker of MaxiK channel. Moreover, it was found that paxilline substantially inhibited HS-induced activation of several different transcription factors in macrophages, including nuclear factor kappaB (NF-κB), p38 and interferon regulatory factor-3 (IRF-3), followed by decreased production of tumor necrosis factor-α (TNF-α) and interferon-β (IFN-β). Taken together, our investigation provides likely evidence that HS/TLR4-mediated intracellular inflammatory cascade depends on the activation of MaxiK, which may offer an important opportunity for a new approach in the therapeutic strategies of SAP. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Oxidative stress and inflammation play important roles in the progression from simple fatty liver to nonalcoholic steatohepatitis (NASH). The aim of this work was to investigate whether treatment with hydrogen sulfide (H2 S) prevented NASH in rats through abating oxidative stress and suppressing inflammation.
A methionine-choline-deficient (MCD) diet rat model was prepared. Rats were divided into three experimental groups and fed for 8 weeks as follows: (1) control rats; (2) MCD-diet-fed rats; (3) MCD-diet-fed rats treated with NaHS (intraperitoneal injection of 0.1 ml/kg/d of 0.28 mol/l NaHS, a donor of H2 S).
MCD diet impaired hepatic H2 S biosynthesis in rats. Treatment with H2 S prevented MCD-diet-induced NASH, as evidenced by hematoxylin and eosin staining, reduced apoptosis and activities of ALT and AST, and attenuated hepatic fat accumulation in rats. Treatment with H2 S abated MCD-diet-induced oxidative stress through reducing CYP2E1 expression, enhancing HO-1 expression and suppressing mitochondrial ROS formation, and suppressed MCD-diet-induced inflammation through suppressing activated NFκB signaling and reducing IL-6 and TNFα expression. In addition, Treatment of MCD-diet fed rats with H2 S had a beneficial modulation on expression profiles of fatty acid metabolism genes in livers.
Treatment with H2 S prevented NASH induced by MCD diet in rats possibly through abating oxidative stress and suppressing inflammation.
Journal of Gastroenterology and Hepatology 10/2013; 29(1). DOI:10.1111/jgh.12389 · 3.50 Impact Factor