Angioimmunoblastic T-cell lymphoma contains multiple clonal T-cell populations derived from a common TET2 mutant progenitor cell.

Angioimmunoblastic T-cell lymphoma (AITL) is a neoplastic proliferation of T follicular helper cells with clinical and histological presentations suggesting a role of antigenic drive in its development. Genetically, it is characterized by a stepwise acquisition of somatic mutations, with early mutations involving epigenetic regulators (TET2, DNMT3A) and occurring in haematopoietic stem cells, with subsequent changes involving signaling molecules (RHOA, VAV1, PLCG1, CD28) critical for T-cell biology. To search for evidence of potential oncogenic cooperation between genetic changes and intrinsic T cell receptor (TCR) signaling, we investigated somatic mutations and T-cell receptor ß (TRB) rearrangement in 119 AITL, 11 peripheral T-cell lymphomas with T follicular helper phenotype (PTCL-TFH), and 25 PTCL-NOS using Fluidigm polymerase chain reaction (PCR) and Illumina MiSeq sequencing. We confirmed frequent TET2, DNMT3A, and RHOA mutations in AITL (72%, 34%, 61%) and PTCL-TFH (73%, 36%, 45%) and showed multiple TET2 mutations (2 or 3) in 57% of the involved AITL and PTCL-TFH. Clonal TRB rearrangement was seen in 76 cases with multiple functional rearrangements (2-4) in 18 cases (24%). In selected cases, we confirmed bi-clonal T-cell populations and further demonstrated that these independent T-cell populations harboured identical TET2 mutations by using BaseScope in situ hybridization, suggesting their derivation from a common TET2 mutant progenitor cell population. Furthermore, both T-cell populations expressed CD4. Finally, in comparison with tonsillar TFH cells, both AITL and PTCL-TFH showed a significant overrepresentation of several TRB variable family members, particularly TRBV19*01. Our findings suggest the presence of parallel neoplastic evolutions from a common TET2 mutant haematopoietic progenitor pool in AITL and PTCL-TFH, albeit to be confirmed in a large series of cases. The biased TRBV usage in these lymphomas suggests that antigenic stimulation may play an important role in predilection of T cells to clonal expansion and malignant transformation. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Disrupted topological organization of the default mode network in mild cognitive impairment with subsyndromal depression: A graph theoretical analysis.

AIMS: Subsyndromal depression (SSD) is common in mild cognitive impairment (MCI). However, the neural mechanisms underlying MCI with SSD (MCID) are unclear. The default mode network (DMN) is associated with cognitive processes and depressive symptoms. Therefore, we aimed to explore the topological organization of the DMN in patients with MCID. METHODS: Forty-two MCID patients, 34 MCI patients without SSD (MCIND), and 36 matched healthy controls (HCs) were enrolled. The resting-state functional connectivity of the DMN of the participants was analyzed using a graph theoretical approach. Correlation analyses of network topological metrics, depressive symptoms, and cognitive function were conducted. Moreover, support vector machine (SVM) models were constructed based on topological metrics to distinguish MCID from MCIND. Finally, we used 10 repeats of 5-fold cross-validation for performance verification. RESULTS: We found that the global efficiency and nodal efficiency of the left anterior medial prefrontal cortex (aMPFC) of the MCID group were significantly lower than the MCIND group. Moreover, small-worldness and global efficiency were negatively correlated with depressive symptoms in MCID, and the nodal efficiency of the left lateral temporal cortex and left aMPFC was positively correlated with cognitive function in MCID. In cross-validation, the SVM model had an accuracy of 0.83 [95% CI 0.79-0.87], a sensitivity of 0.88 [95% CI 0.86-0.90], a specificity of 0.75 [95% CI 0.72-0.78] and an area under the curve of 0.88 [95% CI 0.85-0.91]. CONCLUSIONS: The coexistence of MCI and SSD was associated with the greatest disrupted topological organization of the DMN. The network topological metrics could identify MCID and serve as biomarkers of different clinical phenotypic presentations of MCI.

[Effect of acupuncture at "Houxi" (SI3) and"Huantiao" (GB30) on high mobility group box 1 protein in spinal nerve trunk of rats with lumbar disc herniation].

OBJECTIVE: To observe the effect of acupuncture at "Houxi"(SI3) and "Huantiao"(GB30) on high mobility group box 1(HMGB1) protein and mRNA in spinal nerve trunk(SNT) of rats with lumbar disc herniation(LDH), so as to explore the mechanisms of acupuncture at this paired points on the treatment for LDH. METHODS: SD rats were randomly divided into sham operation, model, conventional acupuncture(CA) and paired points(PP) groups (with 8 rats in each group). The LDH model was established by injection of autologous suspension made from rats' own nucleus pulsus into the epidural space. Rats in the CA group received acupuncture treatment at bilateral "Weizhong"(BL40), "Dachangshu"(BL25) and "Shenshu"(BL23), while rats in the PP group received acupuncture at bilateral SI3 and GB30, 30 min each time, once daily for 14 consecutive days. The thermal pain threshold of bilateral hind feet of rats was detected by thermal pain stimulator. The contents of serum IL-1ß, IL-6 and IL-8 of rats were detected by ELISA. Western blot and immunofluorescence were used to detect the expression of HMGB1 protein in the lumbar(L)5 SNT of rats. The relative expression of HMGB1 mRNA in L5 SNT was determined by qPCR. HE staining was used to observe the morphological changes of L5 SNT. RESULTS: Compared with the sham operation group, the thermal pain threshold of bilateral hind feet in the model group was decreased (P<0.05); compared with the model group, the thermal pain threshold of bilateral hind feet in the CA group and the PP group were increased (P<0.05). The expressions of HMGB1 protein and mRNA in L5 SNT, and the contents of serum IL-1ß, IL-6 and IL-8 of rats in the model group were significantly increased(P<0.000 1, P<0.001) in contrast to the sham operation group. The expressions of HMGB1 protein and mRNA in L5 SNT, and the levels of serum IL-1ß, IL-6 and IL-8 were significantly decreased (P<0.01, P<0.000 1, P<0.001, P<0.05) in the CA and PP group, in comparison with those of the model group. Compared with the CA group, the above indexes of rats in the PP group recovered more significantly (P<0.05,P<0.001, P<0.01,P<0.000 1). The histomorphological results showed scattered and various-sized nerve fibers, vacuolation, a large number of disintegrating myelin sheath and lysed Schwann cells in the model group. Myelin sheaths regeneration, regularly-arranged nerve fibers were seen in the CA group and the PP group, with more obvious histopathological recovery observed in the PP group than the CA group. CONCLUSION: Acupuncture intervention inhibites the expressions of HMGB1 protein and mRNA in rats with LDH, and further reduces the production of IL-1ß, IL-6 and IL-8, which is beneficial to inflammatory response inhibition and pain alleviation. The therapeutic effect of the PP group is more obvious than that of the CA group.

Modeling Methodology for Site Selection Evaluation of Underground Coal Gasification Based on Combination Weighting Method with Game Theory.

The lack of systematic geological work is an essential reason why underground coal gasification (UCG) has not been industrialized for a long time. Building a scientific index system and favorable area evaluation technology for the UCG site selection is the key to breaking through the geological bottleneck. Aiming at the problems of the single index weight determination method, intense subjectivity, and poor reliability of current evaluation models, we put forward an evaluation modeling methodology for the UCG site selection using the combination weighting method with the game theory. The factors of coal resource conditions associated with the potential risk of UCG are systematically analyzed. From the six dimensions of the geological structure, hydrogeology, seam occurrence, coal properties, reserves, and roof lithology, 23 key factors were selected as evaluation indexes to construct a hierarchical model composed of the target layer, category index layer, and index layer. The influence of each index on UCG and its reasonable value range were systematically analyzed. The evaluation index system for UCG site selection was formed. The improved analytic hierarchy process (AHP) was adopted to sequence indices and determine their subjective weight. And the variability, conflict, and information amount of the index data were analyzed by the CRiteria Importance Through Intercriteria Correlation (CRITIC) method to calculate the objective weight. Then, the subjective and objective weights were combined through game theory. On this basis, fuzzy theory was employed to calculate the membership of indices and construct the fuzzy comprehensive judgment matrix. The evaluation model of the UCG site selection was applied to the suitability evaluation of resource conditions of UCG pilot projects at Zhongliangshan (ZLS), Huating (HT), and Shanjiaoshu (SJS) mines in China. The result shows that the resource conditions of HT are the best, followed by ZLS and, finally, SJS, which are consistent with the actual running effects of the three UCG pilot projects. It indicates that the evaluation model can provide a scientific theoretical basis and reliable technical support for the UCG site selection.

Sustained-release oxycodone tablets for moderate to severe painful diabetic peripheral neuropathy: a multicenter, open-labeled, postmarketing clinical observation.

OBJECTIVE: To evaluate the efficacy and safety of sustained-release (SR) oxycodone tablets in the treatment of moderate to severe painful diabetic peripheral neuropathy (DPN). Design. This was a multicenter, randomized, open-labeled study. SETTING: This study was completed in 12 hospitals in China. PATIENTS: A total of 80 Chinese patients undergoing moderate to severe painful DPN. INTERVENTIONS: An initial dose of 10mg is recommended to be taken orally every 12 hours. Dose titration was done appropriately according to pain intensity and adverse reactions. OUTCOME MEASURES: Data record included days, dosage, analgesic efficacy, quality of sleep, adverse events, and combination therapy when patients were treated with SR oxycodone tablets. The continuous observation period was 6 weeks. RESULTS: After medication for 1 week, pain was significantly (P<0.01) relieved from 6.8±1.4 to 2.8±1.6. Onset time was within 45 minutes in nearly 60% of the patients, and within 1 hour in nearly 95% of that ones. More than 90% of the patients achieved stable analgesic dose within 3 days. After using SR oxycodone tablets for 1 week, sleep quality was significantly (P<0.01) improved. In week 1, the average dose of SR oxycodone tablets was 16.63±7.79mg. The average daily dose of most patients was about 20mg after 2 weeks. In all the enrolled patients, 38 (47.5%) had adverse reactions. No serious adverse reactions took place. CONCLUSION: The results of this clinical observation further elaborated the efficacy and safety of SR oxycodone tablets in the treatment of moderate to severe painful diabetic peripheral neuropathy in China.

[Effects of glucagon-like peptide 1(9-36) on endothelial nitric oxide synthase in human umbilical vein endothelial cells].

OBJECTIVE: To explore the effects of glucagon-like peptide 1 (GLP-1(9-36)) on endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial cells (HUVEC). METHODS: HUVEC cultured under the conditions of normal glucose (5.5 mmol/L) or high glucose (16.8 mmol/L) were incubated with 5-5000 pmol/L GLP-1(9-36). NO production was assayed by the nitrate reductase method. The eNOS activities were detected by NOS assay kit, p-eNOS (ser-1177) level and total eNOS protein level by Western blot and eNOS mRNA level by real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Under normal glucose condition, NO productions from HUVEC of 50 - 5000 pmol/L GLP-1(9-36) groups were significantly higher than the control ((41.6 ± 8.1) µmol/L vs (22.2 ± 2.6) µmol/L, P < 0.05). So were eNOS activities in cells (1.76 ± 0.12 vs 1.00 ± 0.00, P < 0.05). Compared with the control group, the levels of eNOS phosphorylation at ser-1177, mRNA and total protein were significantly elevated in the 5000 pmol/L GLP-1(9-36) group. Under high glucose condition, GLP-1(9-36) retained all the above effects. CONCLUSION: GLP-1 (9-36) can increase NO release, eNOS activity and expression in HUVEC. This may be one of the underlying mechanisms for the protective effects of GLP-1(9-36) on cardiovascular system.

[Effect of Film Mulching, Straw Retention, and Nitrogen Fertilization on the N2O and N2 Emission in a Winter Wheat Field].

In order to explore the characteristics of N2O emissions from winter wheat fields in the Loess Plateau under different farming methods and nitrogen levels, the dynamic changes in N2O emissions from rain-fed winter wheat fields were quantified using static box-gas chromatography. Winter wheat 'Xiaoyan22' was used as the material, and a two-factor split area design was adopted. The conventional tillage (CT), straw incorporated into soil (SM), and flat film mulching (FM) were assigned as the main plot, and three nitrogen fertilizer rates (no nitrogen fertilization, 20% nitrogen reduction (144 kg·hm-2), and conventional nitrogen application (180 kg·hm-2)) were assigned as a split plot. Taking CT as a control, the effects of FM and SM on soil N2O emissions under different nitrogen rates were assessed. Furthermore, the correlation between relevant environmental factors and N2O emission flux were analyzed, and N2 emissions were estimated using empirical formulas. The results showed the following:the N2O emissions from the soil of each nitrogen treatment occurred within 20 days, and N2O emission flux peaked within two weeks post-fertilization. The average N2O flux, the total N2O emissions, and the global warming potential of N2O were 1.92-22.75 µg·(m2·h)-1, 0.10-0.46 kg·hm-2, and 26.72-122.15 kg·hm-2, respectively. The N2O emission coefficient of fertilizer nitrogen was 0.05%-0.28%. The total N2 emissions ranged from 0.70-1.82 kg·hm-2. The N fertilization and film mulching significantly increased the N2O emission flux (P<0.05) and the cumulative N2O emissions (P<0.05); however, SM marginally reduced the total N2O emissions. The N2O emission coefficient and global warming potential of fertilizer nitrogen under FM were significantly higher than those under CT and SM (P<0.05). The N2O emissions without nitrogen treatment were only significantly positively correlated with soil water-filled pore spaces (WFPS) (P<0.05); the N2O emissions in the N fertilization condition were significantly positively correlated with WFPS, ω(NO3--N), ω(NH4+-N), and 0-5 cm soil layer temperature (P<0.05). Overall, under the condition of no fertilization, water was the main factor to control the nitrogen transformation and soil N2O emission; nevertheless, under the N fertilization condition, both nitrification and denitrification contributed to the N2O emissions in the rain-fed winter wheat fields. Film mulching practice and nitrogen application markedly increased the N2O emissions, fertilizer nitrogen emission coefficient, and global warming potential in the rain-fed winter wheat fields. Nonetheless, straw incorporated into the soil resulted in a marginal reduction in N2O emissions.

Role of COL3A1 and POSTN on Pathologic Stages of Esophageal Cancer.

BACKGROUND: Esophageal cancer (EC) is a primary malignant tumor originating from the esophageal of the epithelium. Surgical resection is a potential treatment for EC, but this is only appropriate for patients who have locally resectable lesions suitable for surgery. However, most patients with EC are at a late stage when diagnosed. Therefore, there is an urgent need to further explore the pathogenesis of EC to enable early diagnosis and treatment. METHODS: Our study downloaded 2 expression spectrum datasets (GSE92396 and GSE100942) in the Gene Expression Omnibus (GEO) database. GEO2 R was used to identify the Differentially expressed genes (DEGs) between the samples of EC and control. Using the DAVID tool to make the Functional enrichment analysis. Constructing A protein-protein interaction (PPI) network. Identifying the Hub genes. The impact of hub gene expression on overall survival and their expression based on immunohistochemistry were analyzed. Associated microRNAs were also predicted. RESULTS: There were 36 common DEGs identified. The analysis of GO and KEGG results shown that the variations were predominantly concentrated in the extracellular matrix (ECM), ECM organization, DNA binding, platelet activation, and ECM-receptor interactions. COL3A1 and POSTN had high expression in EC tissues which was compared with their expression in healthy tissues. Analysis of pathologic stages showed that when COL3A1 and POSTN were highly expressed, the stage of the pathologic of EC patients was relatively high (P < 0.005). CONCLUSIONS: COL3A1 and POSTN may play an important role in the advancement and occurrence of EC. These genes could provide some novel ideas and basis for the diagnosis and targeted treatment of EC.

SmCOI1 affects anther dehiscence in a male-sterile Solanum melongena line.

Anther indehiscence is an important form of functional male sterility that can facilitate the production of hybrid seed; however, the molecular mechanisms of anther indehiscence-based male sterility have not been thoroughly explored in eggplant (Solanum melongena L.). Here, we used two-dimensional gel electrophoresis to compare the protein profiles in the anthers of normally developing (F142) and anther indehiscent (S16) S. melongena plants. Four differentially expressed proteins were identified using matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry. Of these proteins, the transcript accumulation of the eggplant CORONATINE INSENSITIVE1 (SmCOI1) was significantly downregulated in S16 relative to F142. Phylogenetic analysis showed that SmCOI1 has high amino acid sequence similarity and clustered into the same subgroup as its homologs in other members of the Solanaceae. Subcellular localization analysis showed that SmCOI1 localized to the nucleus. Moreover, reverse-transcription quantitative PCR revealed that the jasmonic acid pathway genes SmJAZ1 and SmOPR3 are upregulated in F142 relative to S16. Protein-protein interaction studies identified a direct interaction between SmCOI1 and SmOPR3, but SmCOI1 failed to interact with SmJAZ1. These findings shed light on the regulatory mechanisms of anther dehiscence in eggplant.

Identification of differentially expressed genes between primary lung cancer and lymph node metastasis via bioinformatic analysis.

Lung cancer (LC), with its high morbidity and mortality rates, is one of the most widespread and malignant neoplasms. Mediastinal lymph node metastasis (MLNM) severely affects postoperative survival of patients with LC. Additionally, the molecular mechanisms of LC with MLNM (MM LC) remain not well understood. To identify the key biomarkers in its carcinogenesis and development, the datasets GSE23822 and GSE13213 were obtained from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified, and the Database for Annotation, Visualization and Integrated Discovery was used to perform functional annotations of DEGs. Search Tool for the Retrieval of Interacting Genes and Cytoscape were utilized to obtain the protein-protein interaction (PPI) network, and to analyze the most significant module. Subsequently, a Kaplan-Meier plotter was used to analyze overall survival (OS). Additionally, one co-expression network of the hub genes was obtained from cBioPortal. A total of 308 DEGs were identified in the two microarray datasets, which were mainly enriched during cellular processes, including the Gene Ontology terms 'cell', 'catalytic activity', 'molecular function regulator', 'signal transducer activity' and 'binding'. The PPI network was composed of 315 edges and 167 nodes. Its significant module had 11 hub genes, and high expression of actin ß, MYC, arginine vasopressin, vesicle associated membrane protein 2 and integrin subunit ß1, and low expression of NOTCH1, synaptojanin 2 and intersectin 2 were significantly associated with poor OS. In summary, hub genes and DEGs presented in the present study may help identify underlying targets for diagnostic and therapeutic methods for MM LC.

Long-term effects of radiation prior to surgery and chemotherapy on survival of esophageal cancer undergoing surgery.

Esophageal cancer (EC) is one of the most common cancers in the world, with continuously growing diagnoses and morbidity. Because it is still unclear how to choose the best treatment for EC patients, a multimodal treatment is necessary to improve the prospect of the malignancy, including a sequence of surgery, chemotherapy, and radiotherapy, whether alone or combination. Therefore, this paper aims to analyze the effect of the sequence of chemotherapy, radiotherapy, and surgery on the prognosis and survival rate of patients with EC.The Surveillance, Epidemiology, and End Results (SEER) database was used to extract a dataset of patients who were diagnosed with EC from 1973 to 2015, with follow-up data for 6 years after diagnosis. The data were analyzed using correlation analysis, logistic regression Cox regression, and Kaplan-Meier analysis.EC patients who had radiation prior to surgery and chemotherapy had a better prognosis than the cases without chemotherapy. Based on univariate logistic regression, the odds radios of vital status recoded for "radiation prior to surgery combined with chemotherapy" is the lowest one among the 8 groups classified by radiation sequence with surgery and chemotherapy (P < .001). Further, radiation prior to surgery and chemotherapy is an independent prognostic factor for better survival among EC patients.In conclusion, in the treatment of EC, administering radiation prior to surgery and chemotherapy is better than no radiotherapy, perioperative radiotherapy, postoperative radiotherapy, and other combinations without chemotherapy.

Genetic effects of polymorphisms of candidate genes associated with ovary development and egg production traits in ducks.

Duck eggs are highly nutritious, and demand for consumption has markedly increased in the growing human population, resulting in the need to increase production. Egg production is dependent on the reproductive performance of animals, a trait that is not highly heritable. Improving reproductive performance, therefore, is an essential aim of breeders performing genetic selection to increase egg production. The ovary has received much attention by breeders because of its importance in the production and release of eggs. The ovary, therefore, has been intensely studied to identify the candidate genes and the polymorphisms associated with egg-laying traits. The expression of these genes in the ovary indicates the potential for involvement in ovarian follicular development. The expression of the growth hormone, follicle-stimulating hormone receptor, prolactin, ovoinhibitor, melatonin receptor, and insulin-like growth factor-2 genes in the ovary has been studied, and polymorphisms have been identified that are related to egg-laying traits. The single nucleotide polymorphisms of these genes help with the identification of novel genetic markers that assist in selecting the ducks with the most desirable genotypes for egg production. This approach to genetic selection is more effective than the traditional method used to select animals for egg production. With this review, therefore, there is a summarization of genetic effects of polymorphisms in candidate genes related to ovarian development and egg production traits in ducks.

Identification of nine microRNAs as potential biomarkers for lung adenocarcinoma.

Lung cancer is a leading global cause of cancer-related death, and lung adenocarcinoma (LUAD) accounts for ~ 50% of lung cancer. Here, we screened for novel and specific biomarkers of LUAD by searching for differentially expressed mRNAs (DEmRNAs) and microRNAs (DEmiRNAs) in LUAD patient expression data within The Cancer Genome Atlas (TCGA). The identified optimal diagnostic miRNA biomarkers were used to establish classification models (including support vector machine, decision tree, and random forest) to distinguish between LUAD and adjacent tissues. We then predicted the targets of identified optimal diagnostic miRNA biomarkers, functionally annotated these target genes, and performed receiver operating characteristic curve analysis of the respective DEmiRNA biomarkers, their target DEmRNAs, and combinations of DEmiRNA biomarkers. We validated the expression of selected DEmiRNA biomarkers by quantitative real-time PCR (qRT-PCR). In all, we identified a total of 13 DEmiRNAs, 2301 DEmRNAs and 232 DEmiRNA-target DEmRNA pairs between LUAD and adjacent tissues and selected nine DEmiRNAs (hsa-mir-486-1, hsa-mir-486-2, hsa-mir-153, hsa-mir-210, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-577, and hsa-mir-4732) as optimal LUAD-specific biomarkers with great diagnostic value. The predicted targets of these nine DEmiRNAs were significantly enriched in transcriptional misregulation in cancer and central carbon metabolism. Our qRT-PCR results were generally consistent with our integrated analysis. In summary, our study identified nine DEmiRNAs that may serve as potential diagnostic biomarkers of LUAD. Functional annotation of their target DEmRNAs may provide information on their roles in LUAD.

The effects of a COX-2 inhibitor meloxicam on squamous cell carcinoma of the esophagus in vivo.

Our previous study showed that aspirin induced apoptosis of esophageal cancer cells in vitro by inhibiting the pathway of NF-kappaB downstream regulation of cyclooxygenase-2. The purpose of this study was to determine if similar changes occurred in vivo in the tumors of patients with SCC of the esophagus who were given a preferential COX-2 inhibitor, meloxicam. Fifty-three patients who had an esophagectomy for SCC were allocated randomly to either a Treatment group (n = 25) or a control group (n = 28). Patients in the Treatment group were given 7.5 mg/day of meloxicam, for between 10 and 14 days before surgery. Patients in the control group did not take any type of NSAID during this time interval. Samples of the tumor taken from the resected specimens were collected. Proliferation and apoptosis were measured by flow cytometry. The concentration of 6-keto-prostaglandin F(1)alpha in cancer tissue was determined by radio-immuno-assay. Expression of COX-2 mRNA was measured with RT-PCR and COX-2 protein levels with Western blot analysis. Nuclear NF-kappaB and cytoplasmic I kappaB protein levels were determined by electrophoretic mobility shift assay and Western blot, respectively. There were significantly more apoptotic cells in the tumors of patients who were using meloxicam. It also decreased the levels of COX-2 mRNA, COX-2 protein and nuclear NF-kappaB protein and increased the cytoplasmic I kappaB protein in the cancer. We conclude that meloxicam induces apoptosis in SCC of the esophagus in vivo by inhibiting the pathway of NF-kappaB downstream regulation of COX-2.

Responses of human sling and clasp fibers to cholecystokinin (CCK) and gastrin through CCK receptors.

BACKGROUND AND AIM: Cholecystokinin (CCK) and gastrin exert their influences via CCK receptors. This research was conducted to look at the responses of the sling and clasp fibers forming the human lower esophageal sphincter (LES) to CCK and gastrin, and the role of CCK receptors in the responses. METHODS: Muscle strips of sling and clasp fibers from the LES were obtained from patients undergoing subtotal esophagectomy. Isometric tension responses of the strips to CCK-8 and gastrin-17 were studied, and the maximum effect (E(max)) for each agonist was derived. CCK-A receptor antagonist, CR1409 and CCK-B antagonist, CR2945 were applied to sling and clasp fibers and their pK(B) values were calculated. RESULTS: Sling fibers produced significant contractions following exposure to CCK-8 and gastrin-17, while clasp fibers had less responses to the two agents. CR1409 and CR2945 inhibited responses of sling to CCK-8 in a concentration-dependent fashion. The inhibition effects of the two antagonists on clasp fibers were not measurable because there was a mild contraction of the fiber in response to CCK-8. CONCLUSION: The contractions generated by sling fibers following exposure to CCK and gastrin are greater than that produced by clasp fibers. CCK-A receptors are more important for the generation of contractions by the sling fibers, whereas both CCK-A and CCK-B receptors are involved in the functional regulation of the clasp fibers. [Corrections added after online publication 28 April 2008: in the Background and Aims section of the preceding abstract, all instances of 'CKK' were corrected to 'CCK'. In the final sentence of the abstract 'CCKA'was corrected to 'CCK-A'. In the article title '(CKK)' was corrected to '(CCK)'.].

Two luminescent lanthanide(iii) metal-organic frameworks as chemosensors for high-efficiency recognition of Cr(vi) anions in aqueous solution.

Two new lanthanide(iii) metal-organic frameworks (MOFs) {[(CH3)2NH2]2[Ln4(FDA)7(DMF)2]·0.5DMF}n [Ln = Eu (1), and Tb (2)] based on furan-2,5-dicarboxylic acid (H2FDA) have been successfully assembled and well characterized in detail. These MOFs are isostructural and demonstrate 12-connected sqc15 topologies, which are rarely observed in MOF chemistry, especially in lanthanide(iii) MOFs. Moreover, these two MOFs could show a tolerance towards moisture and organic solvents and satisfactory chemical stabilities. More importantly, they exhibit sensitive and selective luminescence quenching response towards Cr2O72- and CrO42- anions in aqueous solution with the average quenching Ksv values of 1.25 × 104 L mol-1 (Cr2O72-) and 3.56 × 103 L mol-1 (CrO42-) for 1 and 1.46 × 104 L mol-1 (Cr2O72-) and 4.35 × 103 L mol-1 (CrO42-) for 2 and the detection limits of 1.14 × 10-4 mol L-1 (Cr2O72-) and 1.12 × 10-4 mol L-1 (CrO42-) for 1 and 7.42 × 10-5 mol L-1 (Cr2O72-) and 1.27 × 10-4 mol L-1 (CrO42-) for 2. The high quenching Ksv values and low detection limits make them more feasible in sensing Cr(vi) anions in aqueous solution. The possible detection mechanism has been discussed in detail.

[The effects of blood motilin and gastrin on electrical activity and emptying of the intrathoracic stomach after esophagectomy for cancer].

OBJECTIVE: To observe the effects of blood motilin and gastrin on the electrical activity and emptying of the intrathoracic stomach after esophagectomy for cancer. METHODS: Electrogastrography and determination of blood motilin and gastrin were carried out in 52 subjects, including 20 normal volunteers and 32 esophageal cancer patients before and 1, 3, 6, 12 months after operation. Gastric emptying of radiopaque granula was studied in 35 of the 52 subjects, including 5 normal volunteers, 7 preoperative patients and 23 postoperative patients. RESULTS: The preoperative gastric emptying of radiopaque granula was 28.0 +/- 8.0 pieces 120 second after eating the test meal, significantly less than that of the normal controls [(38.0 +/- 2.0) pieces, t = 3.515, P = 0.006], and decreased to (16.0 +/- 4.8) pieces one month after esophagectomy (t = 6.987, P = 0.000), and then recovered to 16.8 +/- 4.8 one year after surgery but still could not reach normal (t = 9.387, P = 0.0000). Compared with the normal controls, the amplitude of electrogastrogram (EGG) of the preoperative patients was (229 +/- 118) microv, not significantly different from that of the controls [(226 +/- 62) microv, t = 0.085, P = 0.933], and the frequency of EGG of the preoperative patients was (3.1 +/- 0.2) times per minute, not significantly different from that of the controls too [(3.2 +/- 0.1) times per minute, t = 0.872, P = 0.387]. But the frequency and amplitude of EGG of the patients one month after operation were (2.9 +/- 0.3) times per minute and (172 +/- 46) microv respectively, both significantly decreased in comparison with those of the normal controls (t = 2.336, P = 0.024; and t = 3.118, P = 0.003). The amplitude reached normal [(223 +/- 60) microv, t = 0.145, P = 0.885] 1 year after surgery, but the frequency still remained at a low level [(3.0 +/- 0.1) times per minute, t = 2.208, P = 0.033). The level of blood motilin of the preoperative patients was (488 +/- 197) ng/L, significantly higher than that of the controls [(248 +/- 98) ng/L, t = 5.030, P = 0.000], and the blood gastrin level of the preoperative patients was (26 +/- 15) ng/L, significantly higher than that of the controls [(20 +/- 12) ng/L, t = 2.741, P = 0.043]. One year after operation the blood motilin level maintained at a high level [(443 +/- 129) ng/L, t = 3.725, P = 0.001], and the gastrin level remained at a high level too [(48 +/- 23) ng/L, t = 3.703, P = 0.001]. CONCLUSION: Physiologically important, persistent elevation of blood gastrin and motilin in the patients who underwent esophagectomy for cancer facilitates the recovery of electrical activity and emptying of the intrathoracic stomach.

Characterization of a novel cold active and salt tolerant esterase from Zunongwangia profunda.

A novel cold active esterase, EstLiu was cloned from the marine bacterium Zunongwangia profunda, overexpressed in E. coli BL21 (DE3) and purified by glutathione-S transferase (GST) affinity chromatography. The mature esterase EstLiu sequence encodes a protein of 273 amino acids residues, with a predicted molecular weight of 30KDa and containing the classical pentapeptidase motif from position 156 to 160 with the catalytic triad Ser158-Asp211-His243. Although, EstLiu showed 64% similarity with the hypothetical esterase from Chryseobacterium sp. StRB126 (WP_045498424), phylogenetic analysis showed it had no similarity with any of the established family of lipases/esterases, suggesting that it could be considered as a new family. The purified enzyme showed broad substrate specificity with the highest hydrolytic activity against p-nitrophenyl butyrate (C4). EstLiu showed remarkable activity (75%) at 0°Cand the optimal activity at pH 8.0 and 30°C with good thermostability and quickened inactivation above 60°C. EstLiu retained 81, 103, 67 and 78% of its original activity at 50% (v/v) in ethanol, isopropanol, DMSO and ethylene glycol, respectively. In the presence of Tween 20, Tween 80 and Triton X-100, EstLiu showed 88, 100 and 117% of relative activity. It is also co-factor independent. The high activity at low temperature and desirable stability in organic solvents and salts of this novel family esterase represents a good evidence of novel biocatalyst. Overall, this novel enzyme showed better activity than previously reported esterases in extreme reaction conditions and could promote the reaction in both aqueous and non-aqueous conditions, indicating its great potential for industrial applications.

Aspirin induces apoptosis in oesophageal cancer cells by inhibiting the pathway of NF-kappaB downstream regulation of cyclooxygenase-2.

BACKGROUND: Aspirin has potential in the prevention or treatment of oesophageal cancer, the seventh most common cancer in the world, but its mechanism of action is still not certain. METHODS: The oesophageal squamous cell carcinoma cell line TE-13 was cultured with aspirin at different concentrations or for different times. Proliferation and apoptosis were measured by MTT reduction and flow cytometry. Expression of COX-2 mRNA was measured by RT-PCR and COX-2 protein levels with Western blot analysis. Nuclear NF-kappaB and cytoplasmic IkappaB protein levels were determined by electrophoretic mobility shift assay and Western blot, respectively. RESULTS: Aspirin significantly inhibited cell proliferation and induced apoptosis at concentrations of 1, 4, 8 mmol/L. Aspirin dose-dependently decreased the levels of COX-2 mRNA, COX-2 protein and nuclear NF-kappaB protein and increased the cytoplasmic IkappaB protein. CONCLUSION: We conclude that aspirin inhibits the proliferation of, and induced apoptosis in, the cultured TE-13 SCC cell line. These changes correlate with a reduction in COX-2 mRNA and protein expression, prostaglandin synthesis, an inhibition of NF-kappaB nuclear translocation, and an increase in cytoplasmic IkappaB. These results support the further investigation of the cyclooxygenase pathway in investigating the potential of aspirin and similar drugs in cancer prevention and therapy.

[Functional study of the remnant esophagus and intrathoracic stomach in patients who underwent esophagectomy for cancer].

OBJECTIVE: To investigate pathophysiological changes of the remnant esophagus and gastric cardia in patients who underwent esophagectomy for cancer, and to provide objective evidences for the improvement of the postoperative quality of life. METHODS: The function of the remnant esophagus and intrathoracic stomach in patients who underwent esophagectomy for cancer were assessed objectively. The methods that we used were gastric scintigraphy, esophageal manometry, 24-hour esophageal pH monitoring, electronic gastroscopy, videofluoroscopy, and DeMeester scoring system for the assessment of heartburn. Findings were recorded and compared with normal controls. RESULTS: After esophagectomy for cancer, the emptying of intrathoracic stomach was delayed (t = 7.105, P < 0.01) and improved over time, but could not reach normal one year after surgery (t = 2.9, P = 0.016). In patients who had undergone esophagectomy for cancer, the contracting pressure of the upper esophageal sphincter and resting pressure of the remnant esophagus were higher than that in normal controls (t = 2.275, P = 0.03; t = 2.16, P = 0.039 respectively). 89.7% of patients who had undergone esophagectomy had gastroesophageal reflux measured with 24-hour pH monitoring. The extent of reflux was less severe when patients were in a semi-reclining position than in a prostration position (t = 3.074, P = 0.005). CONCLUSION: After esophagectomy for cancer, delayed emptying of the intrathoracic stomach is improved gradually over time, but it is inaccessible to normal level. Gastroesophageal reflux extensively exists in patients who underwent esophagectomy for cancer, but it can be lessened by taking semi-reclining position.