Sodium channel 1 subunit alpha SCNN1A exerts oncogenic function in pancreatic cancer via accelerating cellular growth and metastasis.

The identification of new diagnostic and therapeutic biomarkers might be helpful to understand molecular mechanism of cancer pathogenesis and develop anti-cancer targets. This study reported the alteration of Sodium channel 1 subunit alpha (SCNN1A) expression, its prognostic significance and biological roles in pancreatic cancer. Bioinformatics database was searched to explore the expression of SCNN1A in pancreatic cancer specimens and analysis results were further validated by qRT-PCR and Western blot assay. The correlation between SCNN1A expression and clinicopathological characteristics and its impact on survival outcome of pancreatic cancer patients were investigated using GEPIA database and Kaplan-Meier plotter. Loss- and gain-of-functional experiments in vitro were done to investigate the biological function of SCNN1A in pancreatic cancer. Bioinformatics analysis and validation experiment showed that SCNN1A was frequently overexpressed in pancreatic cancer specimens and cell lines (P < 0.001), and there were significant relevance between high SCNN1A expression and TP53 mutation (P < 0.05) as well as unfavorable prognosis of pancreatic cancer patients (HR for overall survival: 1.9, P = 0.003 and HR for disease-free survival: 1.7, P = 0.014). The silencing of SCNN1A suppressed cell proliferation, migration and invasion and induced cell apoptosis (P < 0.05), while its overexpression promoted aggressive phenotypes of pancreatic cancer cells in vitro (P < 0.05). SCNN1A possessed oncogenic function and its dysregulation could be implicated in the development and metastasis of pancreatic cancer.

Identification of genes and candidate agents associated with pancreatic cancer.

Pancreatic cancer is a malignant neoplasm originating from transformed cells arising in tissues forming the pancreas. A major challenge in current cancer research is biological interpretation of complexity of cancer somatic mutation profiles. It has been suggested that several molecular alterations may play important roles in pancreatic carcinogenesis. In this study, by using the GSE28735 affymetrix microarray data accessible from Gene Expression Omnibus (GEO) database, we identified differentially expressed genes (DEGs) between paired pancreatic cancer tissues and adjacent nontumor tissues, followed the protein-protein interaction of the DEGs. Our study identified thousands of DEGs involved in regulation of cell cycle and apoptosis in progression of pancreatic cancer. Sp1 was predicted to be the major regulator by transcription factors analysis. From the protein-protein interaction networks, we found that Tk1 might play an important role in the progression of pancreatic cancer. Finally, we predicted candidate agents, including tomatidine and nialamide, which may be used as drugs to treat pancreatic cancer. In conclusion, our data provide a comprehensive bioinformatics analysis of genes and pathways which may be involved in the progression of pancreatic cancer.

Isolated pancreatic tuberculosis in non-immunocompromised patient treated by Whipple's procedure: a case report.

PANCREATIC tuberculosis (TB) is a rare disease and its diagnosis is difficult because of the lack of specific clinical manifestations. Computed tomography (CT) and magnetic resonance imaging (MRI) have some diagnostic values in this disease, but it is easy to misdiagnose pancreatic TB as a pancreatic tumor.1 In this article, we present a case of non-immunocompromised patient developing an isolated pancreatic TB, report the CT and MRI findings, and the surgical procedure for it.

CYP3A5*3 polymorphism and cancer risk: a meta-analysis and meta-regression.

CYP3A5 is a cytochrome P450 superfamily member which is involved in the metabolism of drugs, steroid hormones, and other xenobiotics. Emerging evidences suggest that CYP3A5*3 (rs776746 A>G) polymorphism may play a role in the etiology of carcinogenesis and affect an individual's susceptibility to cancer in humans, but individually published studies showed inconclusive results. This meta-analysis aimed to derive a more accurate estimation of the correlation between CYP3A5*3 polymorphism and cancer risk. A literature search of PubMed, Embase, Web of Science, and China BioMedicine databases was conducted on articles published before January 1, 2013. Seventeen case-control studies were included with a total of 7,458 cancer patients and 7,166 healthy controls. The meta-analysis results showed that CYP3A5*3 polymorphism may increase the risk of cancer, especially in acute leukemia, chronic leukemia, and colorectal cancer. However, no statistically significant associations were found in prostate cancer, liver cancer, and other cancers. Further subgroup analysis by ethnicity indicated that CYP3A5*3 polymorphism was associated with an increased risk of cancer among Asian and Caucasian populations, but not among African populations. In conclusion, the current meta-analysis suggests that CYP3A5*3 polymorphism may play an important role in the development of acute and chronic leukemia and colorectal cancer, especially among Asian and Caucasian populations.

Amination of biorefinery technical lignin by Mannich reaction for preparing highly efficient nitrogen fertilizer.

To develop a novel lignin-based highly efficient nitrogen fertilizer, the amination of the biorefinery technical lignin was conducted by Mannich reaction synergy with phenolation pretreatment. Subsequently, the structural transformations of lignin samples and the reaction mechanism were investigated in detail. The soil column leaching experiment was also performed to research the nitrogen release behavior of aminated lignin in soil. The results indicated that the amounts of active sites in lignin were significantly increased to 8.26 mmol/g from the original 2.91 mmol/g by phenolation. In addition, the Mannich reaction was highly selective for occurring at ortho- and para-positions of phenolic hydroxyl groups in the phenolated lignin, in which the latter was favored. Moreover, the nitrogen content in the aminated lignin was highly depended on the types of amination reagent instead of the proportion of reactants in this study. Under an optimal condition, aminated lignin with a high nitrogen content (10.13%) and low C/N ratio (6.08) could be obtained. Besides, it was especially noteworthy that the prepared APL in this study has a favorable nitrogen release behavior in soil. Thus, it is believed that these aminated lignin derivatives could be used for the preparation of various lignin-based highly efficient nitrogen fertilizer.

[Determination of intestinal permeability in cholelithiasis patients by oral administration of technetium-99m-diethylenetriaminepentaacetatic acid].

OBJECTIVE: To investigate the intestinal permeability of patients with cholelithiasis of different types. METHODS: Technetium-99m-diethylenetriaminepentaacetatic acid (99mTc-DTPA) at the dose of 185 MBq (5 mCi) was administered orally to 56 patients of cholelithiasis, 15 cases of cholesterol stone (CS group) and 41 cases of pigment stone (PS group) based on the cross section of the stone during operation, and 17 healthy controls. A 24 h urine collection was obtained after the ingestion of the tracer to calculate the urinary excretion of DTPA. RESULTS: The mean percentage of the total ingested dose of 99mTc-DTPA excreted in a 24 h urinary excretion was 5.0%+/-3.6% in the CS group, not significantly different from that in the control group (4.5%+/-3.4%. F=2.18, P>0.05), and the mean percentage of the total ingested dose of 99mTc-DTPA excreted in a 24 h urinary excretion of the PS group was 10.5%+/-6.9%, significantly higher than that in the control group (F=7.62, P<0.05), showing a significantly increase of intestinal permeability (P<0.05). CONCLUSION: The intestinal permeability of the patients of pigment stone is higher than that of the healthy subjects. Hyperpermeability may be a factor of the pathogenesis of pigment stone.

[The relationship between Oddi's sphincter and bile duct pigment gallstone].

OBJECTIVE: To investigate the relationship between anatomic abnormalities and malfunction of Oddi sphincter with formation of bile duct pigment gallstone. METHODS: One hundred and twenty-three patients with a T tube after cholecystectomy and choledochotomy were divided into reflux group and control group by measuring the amounts of radioactivity of (99m)Tc-DTPA in the bile. Among them 53 were selected randomly to undergo choledochoscopic manometry. Basal pressure of Oddi's sphincter (SOBP), amplitude of Oddi's sphincter (SOCA), frequency of contraction (SOF), duration of contraction (SOD), duodenal pressure (DP), common bile duct pressure (CBDP) were scored and analyzed. The level of plasma motilin and serum gastrin of 45 patients and 12 healthy volunteers were measured by radioimmunoassay. The incidence rates of duodenal descending part diverticulum in patients with bile duct pigment stones, patients without alimentary tract diseases, patients with gallbladder polyps, patients with gallbladder stones were studied by means of barium meal examination. The incidence rates of intraduodenal peri-ampullary diverticulum in patients with primary bile duct pigment stones, patients with bile duct stone and gallbladder stones, patients with bile duct stones originating from the gallbladder, patients with inflammation and stricture of the extremity of bile duct and papilla, patients with cancer of the extremity of bile duct and papilla, patients with post-cholecystectomy syndrome were detected by duodenoscope. RESULTS: Of the patients, 44 were detected with duodenal-biliary reflux (35.8%). SOBP, SOCA and CBDP in the reflux group were much lower than those in control group (P < 0.001). The level of serum gastrin and plasma motilin of the reflux group were much lower than those of control group (P < 0.01). Positive correlation was found between level of motilin and SOBP while level of gastrin was positively correlated with SOBP and CBDP. The incidence of duodenal diverticulum in patients with bile duct pigment stone was 36.62%, which was higher than that of the other 3 groups. The incidence rate of intraduodenal peri-ampullary diverticulum in patients with primary bile duct pigment stone was higher than that of patients with inflammation and stricture of the extremity of bile duct and papilla, patients with cancer of the extremity of bile duct and papilla and patients with bile duct stones originating from the gallbladder. CONCLUSIONS: The patients with bile duct pigment stone have apparent duodenal-biliary reflux and infection of the bile duct. The state of structure and function of Oddi's sphincter is correlated significantly with bile duct pigment stone. The anatomic abnormalities and malfunction of Oddi's sphincter played an important role in the formation of bile duct pigment stone.

Oral (99m)Tc-DTPA simultaneous determination of duodenobiliary reflux and intestinal permeability in patients after choledocholithotomy plus T-tube drainage.

BACKGROUND: The high choledocholithiasis recurrence rate after choledocholithotomy plus T-tube drainage is related to biliary bacterial infection. These bacteria are from the intestine, either via the major duodenal papilla, or the penetrating intestinal mucosa. It is therefore possible that duodenobiliary reflux and increased intestinal permeability exist in patients who have undergone choledocholithotomy. This study was undertaken to find the evidence of duodenobiliary reflux and to assess intestinal permeability in these patients. METHODS: Twenty-one patients who underwent choledocholithotomy plus T-tube drainage 2 months ago, and 11 healthy volunteers (controls) took orally 185MBq of (99m)Tc-DTPA. The patients' bile was collected in the next 2 hours via a T-tube and the (99m)Tc-DTPA radioactivity in the bile was counted. Intestinal permeability was evaluated by measuring the 24-hour urinary excretion rate of ingested (99m)Tc-DTPA in both patients and controls. RESULTS: In 6 of the 21 patients, radioactivity in the bile was detected. The intestinal permeability was significantly higher in patients (11.45%+/-6.16%) than that in controls (3.61%+/-1.63%, t=3.28, P<0.05). CONCLUSIONS: Duodenobiliary reflux exists in patients who have undergone choledocholithotomy plus T-tube drainage. The intestinal permeability is higher in these patients than in healthy subjects. Duodenobiliary reflux and increased intestinal permeability may be factors of cholelithiasis recurrence.

Structural elucidation of inhomogeneous lignins from bamboo.

A better understanding of the inhomogeneous molecular structure of lignin from bamboo is a prerequisite for promoting the "biorefinery" technologies of the bamboo feedstock. A mild and successive method for fractionating native lignin from bamboo species was proposed in the present study. The molecular structure and structural inhomogeneity of the isolated lignin polymers were comprehensively investigated by elemental analysis, carbohydrate analysis, state-of-the-art NMR and analytical pyrolysis techniques (quantitative (13)C NMR, (13)C-DEPT 135 NMR, 2D-HSQC NMR, (31)P NMR, and pyrolysis-GC-MS). The results showed that the proposed method is effective for extracting lignin from bamboo. NMR results showed that syringyl (S) was the predominant unit in bamboo lignin over guaiacyl (G) and p-hydroxyphenyl (H) units. In addition, the lignin was associated with p-coumarates and ferulates via ester and ether bonds, respectively. Moreover, various substructures, such as ß-O-4, ß-ß, ß-5, ß-1, and α,ß-diaryl ether linkages, were identified and quantified by NMR techniques. Based on the results obtained, a proposed schematic diagram of structural heterogeneity of the lignin polymers extracted from the bamboo is presented. In short, well-defined inhomogeneous structures of native lignin from bamboo will facilitate further applications of bamboo in current biorefineries.

Assessment of integrated process based on hydrothermal and alkaline treatments for enzymatic saccharification of sweet sorghum stems.

In this study, sweet sorghum stem was subjected to hydrothermal pretreatment (HTP) and alkaline post-treatment to enhance its saccharification ratio by reducing its recalcitrance. The results showed that the HTP (110-210°C, 0.5-2.0h) significantly degraded hemicelluloses, and the pretreatment at the temperature higher than 190°C led to the partial degradation of the cellulose. As compared to the sole HTP, the integrated process removed most of lignin and hemicelluloses, which incurred a higher cellulose saccharification ratio. Under an optimum condition evaluated (HTP at 170°C for 0.5h and subsequent 2% NaOH treatment), 77.5% saccharification ratio was achieved, which was 1.8, 2.0 and 5.5 times as compared to the only HTP pretreated substrates, alkaline treated substrates alone and the raw material without pretreatment, respectively. Clearly, the integrated process can be considered as a promising approach to achieve an efficient conversion of lignocellulose to fermentable glucose.

Structural elucidation of sorghum lignins from an integrated biorefinery process based on hydrothermal and alkaline treatments.

An integrated process based on hydrothermal pretreatment (HTP) (i.e., 110-230 °C, 0.5-2.0 h) and alkaline post-treatment (2% NaOH at 90 °C for 2.0 h) has been performed for the production of xylooligosaccharide, lignin, and digestible substrate from sweet sorghum stems. The yield, purity, dissociation mechanisms, structural features, and structural transformations of alkali lignins obtained from the integrated process were investigated. It was found that the HTP process facilitated the subsequent alkaline delignification, releasing lignin with the highest yield (79.3%) and purity from the HTP residue obtained at 190 °C for 0.5 h. All of the results indicated that the cleavage of the ß-O-4 linkages and degradation of ß-ß and ß-5 linkages occurred under the harsh HTP conditions. Depolymerization and condensation reactions simultaneously occurred at higher temperatures (≥ 170 °C). Moreover, the thermostability of lignin was positively related to its molecular weight, but was also affected by the inherent structures, such as ß-O-4 linkages and condensed units. These findings will enhance the understanding of structural transformations of the lignins during the integrated process and maximize the potential utilizations of the lignins in a current biorefinery process.

Integrated biorefinery based on hydrothermal and alkaline treatments: investigation of sorghum hemicelluloses.

An integrated process based on hydrothermal pretreatment (HTP) and alkaline post-treatment was proposed to treat sweet sorghum stem. The structural features of the alkali-soluble hemicelluloses (ASHs) obtained from the un-pretreated and hydrothermally pretreated materials were comprehensively investigated by HPAEC, GPC, NMR, FT-IR, and TGA techniques. The ASH with the highest yield (60.6%) was obtained from the HTP residue performed at 130 °C for 1.0 h. All the results indicated that the ASHs had a more linear structure with increasing the pretreatment temperature (110-170 °C). The molecular weights of the ASHs were decreased with increasing the pretreatment temperature, suggesting that C-O bonds in the ASHs were gradually cleaved, especially at the higher temperatures (≥ 170 °C). Interestingly, the integrated process yielded more homogeneous ASHs than hemicelluloses obtained from the un-pretreated material. Based on the spectral analyses, the structure of the ASHs was assumed to be L-arabino-4-O-methyl-D-glucurono-D-xylan.

Adipose-derived stem cells transfected with pEGFP-OSX enhance bone formation during distraction osteogenesis.

This study was designed to investigate the effects of local delivery of adipose-derived stem cells (ADSCs) transfected with transcription factor osterix (OSX) on bone formation during distraction osteogenesis. New Zealand white rabbits (n=54) were randomly divided into three groups (18 rabbits per group). A directed cloning technique was used for the construction of recombinant plasmid pEGFP-OSX, where EGFP is the enhanced green fluorescence protein. After osteodistraction of the right mandible of all experimental rabbits, rabbits in group A were treated with ADSCs transfected with pEGFP-OSX, group B with ADSCs transfected with pEGFP-N1, and group C with physiological saline. Radiographic and histological examinations were processed after half of the animals within each group were humanely killed by injection of sodium pentothal at Week 2 or 6 after surgery. The distraction bone density was measured as its projectional bone mineral density (BMD). Three parameters were measured, namely, the thickness of new trabeculae (TNT), and the volumes of the newly generated cortical bone (NBV1) and the cancellous bone (NBV2) of the distracted regions. Good bone generation in the distraction areas was found in group A, which had the highest BMD, TNT, and NBV in the distraction zones among the groups. There was no significant difference in bone generation in the distraction areas between groups B and C. The results indicate that the transplantation of ADSCs transfected with pEGFP-OSX can effectively promote bone generation during distraction in vivo.

Structural elucidation of lignin polymers of Eucalyptus chips during organosolv pretreatment and extended delignification.

Effective delignification of lignocelluloses is a very important to guarantee the economic feasibility of organosolv-based biorefinery. Eucalyptus chips were successively subjected to organosolv pretreatment (AEOP) and extended delignification (ED) process in the present study. The effects of delignification processes were scientifically evaluated by component analysis, SEM, and CP-MAS NMR techniques. It was found that the integrated process of organosolv pretreatment and subsequent delignification resulted in an effective delignification. The fundamental chemistry of the lignin obtained after these processes was thoroughly investigated by FT-IR, multidimensional NMR ((31)P-, (13)C-, and 2D-HSQC NMR), and GPC techniques. It was observed that an extensive cleavage of aryl ether linkages, ethoxylation, and some condensation reactions occurred in AEOP process, while α-oxidation mainly took place in alkaline hydrogen peroxide (AHP) process. It is believed that better understanding the fundamental chemistry of lignin facilitates the optimization of the delignification process. More importantly, well-defined of lignin polymers will facilitate their value-added applications in current and future biorefineries.

Recent Advances in Characterization of Lignin Polymer by Solution-State Nuclear Magnetic Resonance (NMR) Methodology.

The demand for efficient utilization of biomass induces a detailed analysis of the fundamental chemical structures of biomass, especially the complex structures of lignin polymers, which have long been recognized for their negative impact on biorefinery. Traditionally, it has been attempted to reveal the complicated and heterogeneous structure of lignin by a series of chemical analyses, such as thioacidolysis (TA), nitrobenzene oxidation (NBO), and derivatization followed by reductive cleavage (DFRC). Recent advances in nuclear magnetic resonance (NMR) technology undoubtedly have made solution-state NMR become the most widely used technique in structural characterization of lignin due to its versatility in illustrating structural features and structural transformations of lignin polymers. As one of the most promising diagnostic tools, NMR provides unambiguous evidence for specific structures as well as quantitative structural information. The recent advances in two-dimensional solution-state NMR techniques for structural analysis of lignin in isolated and whole cell wall states (insitu), as well as their applications are reviewed.

Clinical analysis of thyroid carcinoma showing thymus-like differentiation: report of 8 cases.

Thyroid carcinoma showing thymus-like differentiation (CASTLE) is a kind of rare neoplasm of the thyroid gland. Because thyroid CASTLE is rare and difficult to diagnose, its clinicopathologic features have not been well defined, and no universally accepted treatment recommendation is available. We analyzed retrospectively the clinicopathologic data of 8 patients with thyroid CASTLE who underwent surgery and radiotherapy at the Shengjing Hospital of China Medical University between December 2008 and June 2012. All patients accepted radical surgery. All patients accepted postoperative radiotherapy, except one 79-year-old patient. There was no evidence of recurrence or metastasis during the follow-up period. The pattern of immunohistochemical staining was similar to that of thymic carcinoma. Six of 8 CASTLE cases expressed CD5. All 8 CASTLE patients were negatively expressed in thyroglobulin, thyroid transcription factor 1, and calcitonin. Patients with thyroid CASTLE have good outcomes after radical resection and postoperative radiotherapy. Positive CD5 immunoreactivity can contribute to diagnosis of this disease.

Revealing the structural inhomogeneity of lignins from sweet sorghum stem by successive alkali extractions.

To investigate the inhomogeneity of the lignin from sweet sorghum stem, successive alkali treatments were applied to extract lignin fragments in the present study. The successive treatments released 80.3% of the original lignin from the sorghum stem. The chemical structural inhomogeneity of the isolated lignins was comparatively and comprehensively investigated by UV, FT-IR, and NMR spectra. The lignins were found to be predominantly composed of ß-O-4' aryl ether linkages, together with minor amounts of ß-ß', ß-5', ß-1', and α,ß-diaryl ether linkages. In addition, hydroxycinnamic acid (mainly p-coumaric acid), which was found to be attached to lignin, was released and co-precipitated in the lignin fractions isolated in the initial extracting steps, whereas hydroxycinnamic acids (p-coumaric and ferulic acids) were not detected in the subsequently extracted lignin fractions. Moreover, the high proportion of carbon-carbon structures was potentially related to the high amounts of guaiacyl units in the lignin investigated. Thermogravimetric analysis revealed that the higher molecular weights of lignins resulted in relatively higher thermal stability, and the higher content of C-C structures in the lignin probably led to a higher "char residue". These findings suggested that the lignin fractions extracted from sweet sorghum stem by successive alkali extractions had inhomogeneous features in both chemical composition and structure.

Quantitative structures and thermal properties of birch lignins after ionic liquid pretreatment.

The use of ionic liquid (IL) in biomass pretreatment has received considerable attention recently because of its effectiveness in decreasing biomass recalcitrance to subsequent enzymatic hydrolysis. To understand the structural changes of lignin after pretreatment and enzymatic hydrolysis process, ionic liquid lignin (ILL) and subsequent residual lignin (RL) were sequentially isolated from ball-milled birch wood. The quantitative structural features of ILL and RL were compared with the corresponding cellulolytic enzyme lignin (CEL) by nondestructive techniques (e.g., FTIR, GPC, quantitative (13)C, 2D and (31)P NMR). The IL pretreatment caused structural modifications of lignin (cleavage of ß-O-4 ether linkages and formation of condensed structures). In addition, lignin fragments with lower S/G ratios were initially extracted, whereas the subsequently extracted lignin is rich in syringyl unit. Moreover, the maximum decomposition temperature (T(M)) was increased in the order ILL < RL < CEL, which was related to the corresponding ß-O-4 ether linkage content and molecular weight (M(w)). On the basis of the results observed, a possible separation mechanism of IL lignin was proposed.

Successive alkali extraction and structural characterization of hemicelluloses from sweet sorghum stem.

Sweet sorghum stem was successively extracted with water at 90 °C, 0.3, 0.6, 1.0, 1.5, and 2.0% KOH aqueous solution, and 60% ethanol containing 2.5% KOH at 75 °C for 3 h, yielding 76.3% of the original hemicelluloses. Chemical composition and structural characterization of the seven hemicellulosic fractions obtained were comparatively investigated by a combination of HPAEC, GPC, FT-IR, (1)H-, (13)C-, HSQC NMR and TGA techniques. According to the spectral analysis, hemicelluloses from sweet sorghum stem are assumed to L-arabino-4-O-methyl-D-glucurono-D-xylan. In addition, the higher molecular weights of hemicelluloses resulted in a higher thermal stability of the samples. The present study suggests that successive alkali extraction is a promising approach for fractionation of hemicelluloses from sweet sorghum stem and to prepare hemicellulosic polymers with different branching and molecular weights.

Environmentally friendly microwave ionic liquids synthesis of hybrids from cellulose and AgX (X=Cl, Br).

The purpose of this article was to explore an environmentally friendly strategy to synthesis of biomass-based hybrids. Herein, microwave-assisted ionic liquids method was applied to fabricate the hybrids from cellulose and AgX (X=Cl, Br) using cellulose and AgNO3. The ionic liquids act simultaneously as a solvent, a microwave absorber, and a reactant. Ionic liquids provided Cl(-) or Br(-) to the synthesis of AgCl or AgBr crystals; thus no additional reactant is needed. The products are characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectrometry (FTIR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and differential thermal analysis (DTA). The cellulose-Ag/AgCl hybrid and cellulose-Ag/AgBr hybrid were also obtained by using cellulose-AgCl and cellulose-AgBr hybrids as precursors. This environmentally friendly microwave-assisted ionic liquids method is beneficial to the hybrids with high dispersion.