3D porous metal-organic framework for selective adsorption of methane over dinitrogen under ambient pressure.

We report a highly porous 3D metal-organic framework (MOF) that shows potential for coal mine methane (CMM) capture.

Who may benefit from robotic gastrectomy?: A subgroup analysis of multicenter prospective comparative study data on robotic versus laparoscopic gastrectomy.

AIMS: Robotic gastrectomy for gastric cancer has been proven to be a feasible and safe minimally invasive procedure. However, our previous multicenter prospective study indicated that robotic gastrectomy is not superior to laparoscopic gastrectomy. This study aimed to identify which subgroups of patients would benefit from robotic gastrectomy rather than from conventional laparoscopic gastrectomy. METHODS: A prospective multicenter comparative study comparing laparoscopic and robotic gastrectomy was previously conducted. We divided the patients into subgroups according to obesity, type of gastrectomy performed, and extent of lymph node dissection. Surgical outcomes were compared between the robotic and laparoscopic groups in each subgroup. RESULTS: A total of 434 patients were enrolled into the robotic (n = 223) and laparoscopic (n = 211) surgery groups. According to obesity and gastrectomy type, there was no difference in the estimated blood loss (EBL), number of retrieved lymph nodes, complication rate, open conversion rate, and the length of hospital stay between the robotic and laparoscopic groups. According to the extent of lymph node dissection, the robotic group showed a significantly lower EBL than did the laparoscopic group after D2 dissection (P = 0.021), while there was no difference in EBL in patients that did not undergo D2 dissection (P = 0.365). CONCLUSION: Patients with gastric cancer undergoing D2 lymph node dissection can benefit from less blood loss when a robotic surgery system is used.

Triiodothyronine induces proliferation of pancreatic ß-cells through the MAPK/ERK pathway.

BACKGROUND: 3,5,3'-Triiodothyronine (T3) has a stimulatory effect on cellular growth via thyroid hormone receptors (TRs) in several cell lines. TR expression in the pancreas suggests that pancreatic beta cell proliferation might be induced by T3. The purpose of this study was to demonstrate that T3 induces pancreatic beta cell proliferation through the mitogen activated protein kinase/extracellular regulated kinase (MAPK/ERK) pathway. METHODS: INS-1 cells were plated as a monolayer at densities of 4×104, cultured in RPMI 1,640 with 10% fetal bovine serum with 2-mercaptoethanol, respectively, in 6-well multiplates. After 48 h, they were exposed to 10-7 M T3 or to vehicle alone. Viable cells were harvested after 24, 48, and 72 h of continuous exposure. Cell proliferation and TRα1 and TRß1 expression were analyzed by flow-assisted cell sorting analysis, Ki-67 staining, and Western blotting. The p38 MAPK, ERK, and Akt pathways were analyzed by Western blotting. Beta cell function was evaluated by assaying insulin secretion. RESULTS: T3 enhanced INS-1 cell proliferation at a dose of 10-7 M in a time-dependent manner via the MAPK/ERK pathway and promoted insulin secretion. CONCLUSIONS: Our results demonstrate that MAPK/ERK pathway plays an important role in the T3 induced pancreatic beta cell proliferation.

ZNF313 is a novel cell cycle activator with an E3 ligase activity inhibiting cellular senescence by destabilizing p21(WAF1.).

ZNF313 encoding a zinc-binding protein is located at chromosome 20q13.13, which exhibits a frequent genomic amplification in multiple human cancers. However, the biological function of ZNF313 remains largely undefined. Here we report that ZNF313 is an ubiquitin E3 ligase that has a critical role in the regulation of cell cycle progression, differentiation and senescence. In this study, ZNF313 is initially identified as a XIAP-associated factor 1 (XAF1)-interacting protein, which upregulates the stability and proapoptotic effect of XAF1. Intriguingly, we found that ZNF313 activates cell cycle progression and suppresses cellular senescence through the RING domain-mediated degradation of p21(WAF1). ZNF313 ubiquitinates p21(WAF1) and also destabilizes p27(KIP1) and p57(KIP2), three members of the CDK-interacting protein (CIP)/kinase inhibitor protein (KIP) family of cyclin-dependent kinase inhibitors, whereas it does not affect the stability of the inhibitor of CDK (INK4) family members, such as p16(INK4A) and p15(INK4B). ZNF313 expression is tightly controlled during the cell cycle and its elevation at the late G1 phase is crucial for the G1-to-S phase transition. ZNF313 is induced by mitogenic growth factors and its blockade profoundly delays cell cycle progression and accelerates p21(WAF1)-mediated senescence. Both replicative and stress-induced senescence are accompanied with ZNF313 reduction. ZNF313 is downregulated during cellular differentiation process in vitro and in vivo, while it is commonly upregulated in many types of cancer cells. ZNF313 shows both the nuclear and cytoplasmic localization in epithelial cells of normal tissues, but exhibits an intense cytoplasmic distribution in carcinoma cells of tumor tissues. Collectively, ZNF313 is a novel E3 ligase for p21(WAF1), whose alteration might be implicated in the pathogenesis of several human diseases, including cancers.

Opposite functions of HIF-α isoforms in VEGF induction by TGF-ß1 under non-hypoxic conditions.

Transforming growth factor (TGF)-ß1 has biphasic functions in prostate tumorigenesis, having a growth-inhibitory effect in the early stages, but in the late stages promoting tumor angiogenesis and metastasis. We demonstrate here that tumor-producing TGF-ß1 induces vascular endothelial growth factor (VEGF) in prostate cancer cells, and hypoxia-inducible factor (HIF)-1α and HIF-2α has opposite functions in TGF-ß1 regulation of VEGF expression under non-hypoxic conditions. The promoter response of VEGF to TGF-ß1 was upregulated by the transfection of HIF-2α or siHIF-1α but downregulated by HIF-1α and siHIF-2α. Both HIF-1α and HIF-2α were induced by TGF-ß1 at mRNA and protein levels, however, their nuclear translocation was differentially regulated by TGF-ß1, suggesting its association with their opposite effects. VEGF induction by TGF-ß1 occurred in a Smad3-dependent manner, and the Smad-binding element 2 (SBE2, -992 to -986) and hypoxia response element (-975 to -968) in the VEGF promoter were required for the promoter response to TGF-ß1. Smad3 cooperated with HIF-2α in TGF-ß1 activation of VEGF transcription and Smad3 binding to the SBE2 site was greatly impaired by knockdown of HIF-2α expression. Moreover, the VEGF promoter response to TGF-ß1 was synergistically elevated by co-transfection of Smad3 and HIF-2α but attenuated by HIF-1α in a dose-dependent manner. Additionally, TGF-ß1 was found to increase the stability of VEGF transcript by facilitating the cytoplasmic translocation of a RNA-stabilizing factor HuR. Collectively, our data show that tumor-producing TGF-ß1 induces VEGF at the both transcription and post-transcriptional levels through multiple routes including Smad3, HIF-2α and HuR. This study thus suggests that autocrine TGF-ß1 production may contribute to tumor angiogenesis via HIF-2α signaling under non-hypoxic conditions, providing a selective growth advantage for prostate tumor cells.

Indication for endoscopic mucosal resection in early signet ring cell gastric cancer.

BACKGROUND: The aim of this study was to compare the clinicopathological characteristics of an early signet ring cell carcinoma (SRC) with an early undifferentiated carcinoma (mucinous, poorly differentiated adenocarcinoma) and early differentiated carcinoma (well or moderately differentiated tubular adenocarcinoma, papillary adenocarcinoma) and find indications for endoscopic mucosal resection (EMR) in early SRC. METHODS: 1520 patients with early gastric cancer (EGC), who underwent a curative gastrectomy, were analyzed retrospectively. Among them, 388 patients with SRC were compared with 253 patients with undifferentiated carcinoma (UDC) and 879 with a differentiated carcinoma (DC). RESULTS: SRC was more common in young female patients than UDC. SRC had a tendency to be confined to the mucosa, with smaller size than UDC. The lymph node metastasis rate for SRC was lower than that for UDC, but similar to that of DC. Multivariate analysis revealed lymph node metastasis (LNM) to be associated with the depth of invasion, tumor size, histological type, and lymphatic involvement. SRC had no LNM in the case of a mucosal tumor, smaller than 2 cm, and in the absence of lymphatic involvement. The prognosis of SRC was more favorable than UDC. CONCLUSIONS: Early SRC has different characteristics from early UDC. In view of the lower rate of lymph node metastasis and better prognosis, we suggest that EMR can be performed on patients with early SRC limited to the mucosa, less than 2cm in size, and with no lymphatic involvement.

Quantum chemistry predicted correlations between geometric isomerism (conformation) of -OH and =NH substituents and typical group frequencies of nucleic acid bases: cytosine.

Results of a search for correlations between typical group mode frequencies and conformation of -OH and =NH substituents is reported. The study is based on quantum chemical data (HF/6-31G (d, p) and MP2 (full)/6-31G (d, p) approximations) of 13 isomers of cytosine. It is closely related to investigations of stability and energetics of all isomers of the more common nucleic acid bases, which revealed correlations between conformation (geometric isomerism) of OH and =NH substituents on the one hand and conversion energies, relaxation of internal structural parameters, electric field gradients, etc. on the other hand. In the majority of cases alteration of conformation of these substituents is accompanied by systematic frequency shifts of stretching, in-plane and out-of-plane bending (torsional) modes conventionally assigned to such groups and by alteration of quantum chemically predicted estimates of harmonic valence force constants and structural parameters dominating the mode frequencies. For identification of group modes 'fractional' mass (other than 'natural' mass) isotope shifts of frequency and normal vectors proved useful. Likewise, estimation of effects of force constant and structural parameter alterations on frequency shifts by first order perturbation theory of the FG problem of partial structures contributed valuable insight into the origin of the shifts.

Evaluation of a bar-code system for nutrient analysis in dietary surveys.

OBJECTIVE: A novel system for nutrient analysis has been developed and tested over 5 years. Its key features are a nutrient database of 600 commonly eaten foods (95% of foods eaten in 7-day surveys); a booklet identifying each food with a bar code, bar codes for gram weight and for portion sizes (small, medium, large) and a bar-code reader with dietary analysis software for PCs. In the present study the bar-code system has been evaluated by comparison with a commonly used manual entry nutrient analysis software for dietitians' use. DESIGN: Cross-sectional. SETTING: Glasgow city district. SUBJECTS: One hundred and sixty adults aged 18-65 years old. RESULTS: Comparing mean intakes for macro- and micronutrients, using the Bland and Altman method, the bias between the two methods was small, ranging from 0.93 to 1.03. The bar-code system took significantly less professional time in data entry and nutrient analysis than the widely used manual system (29min per 7-day diary vs. 47 min per 7-day diary, P < 0.001). CONCLUSIONS: It is suggested that the bar-code system offers greater speed with a saving of professional time needed for nutrient analysis of dietary surveys. This system is commended for maintaining accuracy while promoting economy.

A routine method for the simultaneous measurement of retinol, alpha-tocopherol and five carotenoids in human plasma by reverse phase HPLC.

We describe a simple isocratic HPLC method for the accurate and precise measurement of retinol, alpha-tocopherol and the major carotenoids in plasma using UV detection. Reference ranges for retinol, alpha-tocopherol and five carotenoids are determined in a healthy population group. The most abundant carotenoids found in plasma were beta-carotene, lycopene, lutein and cryptoxanthin. Retinol, alpha-tocopherol and carotenoids were determined simultaneously using two internal standards, retinol acetate for retinol and tocopherol acetate for alpha-tocopherol and carotenoids. The use of echinenone as an internal standard for carotenoids was investigated. The protective effect of an antioxidant (ascorbic acid) on the stability of samples and extracted material is documented. The method is useful for the routine measurement of plasma retinol, alpha-tocopherol and carotenoids and could also be used in large scale epidemiological studies.

Effect of inflammation on measures of antioxidant status in patients with non-small cell lung cancer.

This study examined the effect of an inflammatory response on measures of antioxidant status in patients with non-small cell lung cancer (NSCLC). In healthy, control subjects (n = 13) and NSCLC patients (n = 22) fasting concentrations of albumin, C-reactive protein, cholesterol, and the antioxidants alpha-tocopherol, retinol, lutein, lycopene, and alpha- and beta-carotene were measured. The two groups were similar in terms of age, sex, and body mass index. However, the cancer group had an inflammatory response as evidenced by significantly increased C-reactive protein concentrations. Concentrations of all the measured antioxidants of the NSCLC group were significantly lower than those of the control group (P < 0.01). The lowest concentrations were those of the carotenoids lycopene and alpha- and beta-carotene. In the cancer group there were significant negative correlations between concentrations of C-reactive protein and retinol (r = -0.682, P < 0.01), alpha-tocopherol (r = -0.464, P < 0.05), and lutein (r = -0.599, P < 0.01). The results of this study have implications for the interpretation of circulating antioxidant concentrations in patients with NSCLC.

Abnormal antioxidant vitamin and carotenoid status in chronic renal failure.

Oxidative modification of plasma lipoproteins increases their atherogenicity. Nutritive antioxidants, including carotenoids, can prevent such lipoperoxidation and may protect against atherosclerosis. Plasma retinol, ascorbate, alpha-tocopherol and four carotenoids (lutein, lycopene, alpha-carotene and beta-carotene) were measured using HPLC in 45 patients with chronic renal failure (CRF) and in 21 controls. Plasma retinol was significantly increased in patients with CRF (conservative therapy mean of 3.7 mumol/l vs. 1.9 mumol/l; p < 0.001). Plasma lycopene was significantly lower in patients with CRF (healthy mean 0.44 mumol/l vs. conservative therapy mean 0.27 mumol/l and haemodialysis mean of 0.17 mumol/l; p < 0.001), a finding that persisted even after adjusting for plasma cholesterol. Low circulating antioxidant lycopene levels may contribute to an already impaired antioxidant defence system in patients with CRF. The process of haemodialysis further compromises antioxidant defences, principally by removing water-soluble ascorbate and urate, but does not appear to affect circulating carotenoid concentrations.

A new quantum chemical approach in QSAR-analysis. Parametrisation of conformational energies into molecular descriptors JMn (steric) and JSn (electronic).

Two new types of structure-related molecular descriptors, JMn and JSn, have been developed using conformational energies from quantum chemical calculations. For this purpose propipocaine (CAS 3670-68-6) was chosen as a model and 42 analogues were studied. The quantum chemical calculations were performed applying AM1 and PCILO approximation methods. Appropriate mathematical models were designed to calculate steric parameter log JM1 and electronic parameters JS1 to JS6. The values obtained for these parameters were used in multiple linear regression analysis for the evaluation of the structure-activity relationship. Furthermore, a comparison between electronic parameters JSn and sigma (Hammett) was made. The results show, that these parameters can be used successfully in predicting the biological activity of compounds in this model. Although, JS5 values are comparable to sigma-Hammett, the electronic parameter JS2 gives a better correlation in QSAR-analysis involving two parameters JS2 and log JM1.

A PCILO study of the pharmacologically active conformation of local anesthetics of the procaine type. Conformational analysis and complex formation of protonated 2-diethylaminoethyl-acetate with formate anion.

To rationalize and improve receptor selectivity of local anesthetics of the procaine type a dynamic two-center model of the pharmacon-receptor interaction is suggested. A quantum chemical study within the Perturbation Configuration Interaction using Localized Orbitals (PCILO) approximations is carried out to find indications for a conformational change of this flexible drug from its thermodynamically preferred conformation to its pharmacologically active one. For this purpose, the pharmacon-receptor interaction is simulated quantum chemically by the interaction of the local anesthetic model compound 2-diethylaminoethyl-acetate (acetylcaine) with the one-center receptor model formate anion and the two-center receptor model gamma-aminobutyric acid in its zwitterionic form. In the present study, the conformational behaviour of acetylcaine is investigated in detail, confirming this molecule to be an appropriate model for procaine. In its formate complex the preferred conformation of acetylcaine is still retained with regard to the torsional angle of the [OCCN] fragment. Artefacts of the in-vacuo condition of the calculation are discussed. In view of the proposed interaction model, the importance of the first interaction of acetylcaine with the anionic receptor site is found to be in the fixation of the local anesthetic at the receptor surface, due to the long-range character of this interaction. Furthermore, an increased polarity of the carbonyl group of acetylcaine due to this interaction may enhance the proposed second interaction with the receptor.

Blood coagulation monitoring and anticoagulant therapy after liver resection: brief report.

In this sample of 140 patients undergoing hepatic resection to remove cancerous tissue, hypercoagulation was the most common postoperative BCD; in ten patients, this complication led to hepatic failure and hepatic coma. These findings differ from those previously reported in the literature, possibly because our patients had advanced hepatomas which had already infiltrated the great vessels of the liver, and/or the remaining liver was seriously cirrhotic. We found that blood-coagulation monitoring and anticoagulation therapy yielded encouraging results, and it is our hope that this treatment in combination with immunotherapy will prolong the survival of these patients.