Predictive nomogram for lymph node metastasis and survival in gastric cancer using contrast-enhanced computed tomography-based radiomics: a retrospective study.

Background: Lymph node involvement significantly impacts the survival of gastric cancer patients and is a crucial factor in determining the appropriate treatment. This study aimed to evaluate the potential of enhanced computed tomography (CT)-based radiomics in predicting lymph node metastasis (LNM) and survival in patients with gastric cancer before surgery. Methods: Retrospective analysis of clinical data from 192 patients diagnosed with gastric carcinoma was conducted. The patients were randomly divided into a training cohort (n = 128) and a validation cohort (n = 64). Radiomic features of CT images were extracted using the Pyradiomics software platform, and distinctive features were further selected using a Lasso Cox regression model. Features significantly associated with LNM were identified through univariate and multivariate analyses and combined with radiomic scores to create a nomogram model for predicting lymph node involvement before surgery. The predictive performance of radiomics features, CT-reported lymph node status, and the nomogram model for LNM were compared in the training and validation cohorts by plotting receiver operating characteristic (ROC) curves. High-risk and low-risk groups were identified in both cohorts based on the cut-off value of 0.582 within the radiomics evaluation scheme, and survival rates were compared. Results: Seven radiomic features were identified and selected, and patients were stratified into high-risk and low-risk groups using a 0.582 cut-off radiomics score. Univariate and multivariate analyses revealed that radiomics features, diabetes mellitus, Nutrition Risk Screening (NRS) 2002 score, and CT-reported lymph node status were significant predictors of LNM in patients with gastric cancer. A predictive nomogram model was developed by combining these predictors with the radiomics score, which accurately predicted LNM in gastric cancer patients before surgery and outperformed other models in terms of accuracy and sensitivity. The AUC values for the training and validation cohorts were 0.82 and 0.722, respectively. The high-risk and low-risk groups in both the training and validation cohorts showed significant differences in survival rates. Conclusion: The radiomics nomogram, based on contrast-enhanced computed tomography (CECT ), is a promising non-invasive tool for preoperatively predicting LNM in gastric cancer patients and postoperative survival.

Preoperative Splenic Density for the Prediction of Survival and Adjuvant Chemotherapy Benefits in Gastric Cancer.

Background: We aimed to determine whether splenic features change during tumor progression by evaluating the clinicopathological characteristics relevant to splenic density in patients with gastric cancer (GC) and identify a new predictive indicator of prognosis and chemotherapy benefits. Methods: In the present analysis, 408 patients who underwent gastrectomy were included. Density was expressed in mean spleen Hounsfield units on computed tomography. Other clinical characteristics and detailed follow-up data were collected. The cutoff splenic density was 47.8 by the Xtile software. The R software was used for characteristic differential analysis in patients with different splenic densities. The Cox proportional hazards model and forest plot were used for prognosis and chemotherapy benefit analyses. Results: Patients with low splenic density had significantly worse 3-year disease-free survival (DFS) and overall survival (OS) rates (high vs low splenic density: DFS, 63.4% vs 44.6%, p<0.001; OS, 69.8% vs 52.4%, p<0.001). Splenic density showed strong negative correlations with age, number of metastasized lymph nodes, tumor size, and depth of tumor invasion. The benefits of adjuvant chemotherapy were better in the low splenic density group (hazard ratio of OS, 0.546; p=0.001) than in the low-density group (hazard ratio of OS, 0.701; p=0.106). Conclusions: Patients with low splenic density tended to have more advanced tumors and poor prognosis, but better chemotherapy benefits. Splenic density can be regarded as a new indicator of chemotherapy benefits and increase the accuracy of preoperative staging evaluation. Moreover, preoperative evaluation of splenic density may help establish individualized treatment strategies.

Diffuse Reduction of Spleen Density Is an Independent Predictor of Post-Operative Outcomes After Curative Gastrectomy in Gastric Cancer: A Multi-Center Study.

Objectives: The present study aimed to explore the association between spleen density and post-operative outcomes of patients after curative gastrectomy. Methods: From June 2014 to December 2015, we conducted a retrospective study to analyze pertinent clinical data from gastric cancer patients who underwent gastrectomy at the First and the Second Affiliated Hospital of Wenzhou Medical University. Spleen density was determined via computed tomography scans. Univariate and multivariate analyses were performed to determine the risk factors associated with post-operative outcomes after gastric cancer surgery. Results: Three hundred and ninety five patients were included, of whom 98 (24.8%) were defined as having a diffuse reduction of spleen density based on diagnostic cutoff values (spleen density ≤43.89 HU). Multivariate analysis revealed diffuse reduction of spleen density as an independent risk factor for post-operative complications and long-term overall survival. Conclusions: Spleen density can predict severe postoperative complications and long-term overall survival in gastric cancer patients. As an imaging evaluation method, spleen density is a novel tool can be used in clinical as a prognostic predictor for patients with gastric cancer.

Study on the optical and biological properties in vitro of IR808-PEG-FA.

IR808, an IR780 derivative, is capable of fluorescently imaging and photodynamic therapy in vitro and in vivo. However, its application is greatly hampered by hydrophobicity, toxicity and nonspecific delivery to the targeting tissue and that causes accumulation in the liver and kidney. In order to overcome these limitations, we prepared IR808-PEG-FA from IR808, amino-terminated poly(ethylene glycol) (NH2 -PEG-NH2 , denoted as PEG) and folate (FA). PEG, an accepted hydrophilic medicinal agent, was introduced to improve hydrophobicity, and FA was used to increase targeting ability of the conjugate. The obtained product provides a good water solubility and stronger light intensity in near infrared (NIR)-imaging, and CCK-8 test demonstrated which had no appreciable toxicity. In addition, the cell uptake results indicated that IR808-PEG-FA was specifically targeted to positive tumors cells with folate receptor (FR) compared with IR808, and thus it may be used as a novel diagnostic agent or imaging-guided agent for cancer treatment. So this article provides a way to improve hydrophobicity, optical stability and targeting ability in the field of nano-probe for fluorochromes.

Simultaneous determination of tocopherols, carotenoids and phytosterols in edible vegetable oil by ultrasound-assisted saponification, LLE and LC-MS/MS.

A method was developed to simultaneously determine eight bioactive compounds in edible oil based on ultrasound-assisted saponification, liquid-liquid extraction and liquid chromatography coupled with tandem mass spectrometry. Central composite design was employed to optimize ultrasonic temperature and time of saponification. Sample treatment was conducted by ultrasound-assisted saponification at temperature of 75 °C for 40 min. Limits of detection and limits of quantification ranged from 2.0 to 3.2 and from 6.1 to 10.0 ng/mL, respectively. Linear correlations were obtained (R2 > 0.99) and the recoveries at three spiked levels were between 81.7% and 112.0%. This method was employed to determine eight compounds in camellia oils and olive oils. As results, the contents of stigmasterol, δ-tocopherol, γ-tocopherol, ß-carotene and lutein in camellia oils were significantly higher than those in olive oils (p < 0.05). The proposed method can be successfully used to determination of these eight active compounds in camellia oil and other edible oils.

Activated TNF-α/RIPK3 signaling is involved in prolonged high fat diet-stimulated hepatic inflammation and lipid accumulation: inhibition by dietary fisetin intervention.

Increasing evidence indicates that high-fat diet (HFD) is a predisposing factor for metabolic syndrome-associated systemic inflammation and nonalcoholic fatty liver disease (NAFLD). Tumor necrosis factor-α/receptor-interacting protein kinase 3 (TNF-α/RIPK3) axis has recently become regarded as an important regulator and contributor in many inflammation-related diseases. Fisetin (Fn) is a bioactive flavonoid polyphenol with anti-inflammatory and anti-tumor activity. Lately it has gained increasing attention due to its potential advantages in prevention of tumors, metabolic disorders, neuroinflammation and chronic liver injury. However, its role in NAFLD is still not fully understood. Thus, we studied whether prolonged HFD causes TNF-α/RIPK3 activation-associated hepatic steatosis, further evaluating the protective effects of Fn in HFD-fed mice. As expected, HFD promotes metabolic syndrome and pro-inflammatory cytokine generation in serum, enhances liver inflammatory infiltration-related lipid accumulation by increase of TNF-α/RIPK3 activation, ultimately resulting in development of nonalcoholic steatohepatitis. In contrast to this, dietary Fn intervention could suppress metabolic disorder and HFD-triggered hepatic function loss, downregulate TNF-α/RIPK3 signaling-associated hepatic inflammation, balance lipid metabolism-related gene expression, and finally inhibit lipid accumulation and steatohepatitis. Hence, Fn restrains HFD-induced hepatic inflammation and lipid deposition by downregulating metabolic disorder and excessive liver inflammation-associated TNF-α/RIPK3 axis activation.

Evaluation and comparison of in vitro antioxidant activities of unsaponifiable fraction of 11 kinds of edible vegetable oils.

The radical scavenging capabilities of the extracts from eleven edible vegetable oils were investigated by using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-3- ethylbenzothiazoline-6-sulfonic acid (ABTS), and ferric reducing ability of plasma (FRAP) assays. The results indicated that rapeseed oil and sesame oil showed higher radical scavenging abilities than other vegetable oils. When the radical scavenging capabilities of the extracts from virgin camellia oils and commercially available refined camellia oils were evaluated by FRAP assay, the results showed that the antioxidant capabilities of the former were higher than the latter. Therefore, it is recommended that moderate refining processes should be taken to minimize the loss of antioxidant components and people consume virgin oils or less processed edible vegetable oils for higher antioxidant activities.

PLA-PEG-FA NPs for drug delivery system: Evaluation of carrier micro-structure, degradation and size-cell proliferation relationship.

In this paper, the micro-structure of amphiphilic copolymer Polylactic acid-Polyethylene glycol-Folate (PLA-PEG-FA) was studied firstly by a differential scanning calorimetry (DSC). During the process of nanoparticles (NPs) preparation, we found good inter-structure consistency of polymer was the precondition for forming into stable NPs, and those with micro-phase separation structure were prepared of NPs within limits. Hemolytic test and CCK-8 assay results demonstrated the biotoxicity of both NPs and whose leaching liquor was far below related toxicity standards. Two kinds of cell, human breast cancer cell line (MCF-7) and human umbilical vein endothelial cells (EC), showed different manners in test of NPs size-cell proliferation relationship, respectively. Monitored by a nuclear magnetic resonance (NMR) and a gel permeation chromatography (GPC), the degradation behavior of NPs in aqueous solution indicated amide bond break more difficultly than ester bond, and FA classic proton peak disappeared in the third week, meanwhile lactic acid (LA) unit number became 25% of the initial. Finally the NPs was completely degraded in the eighth week. In the whole process, NPs underwent a change from compact to loose state. We hope these results will benefit to improve design of drug delivery system in nanomedicine, which could offer the selection rule for amphiphilic polymer NPs on material and size.

Apigenin Inhibits Human SW620 Cell Growth by Targeting Polyamine Catabolism.

Apigenin is a nonmutagenic flavonoid that has antitumor properties. Polyamines are ubiquitous cellular polycations, which play an important role in the proliferation and differentiation of cancer cells. Highly regulated pathways control the biosynthesis and degradation of polyamines. Ornithine decarboxylase (ODC) is the rate-limiting enzyme in the metabolism, and spermidine/spermine-N1-Acetyl transferase (SSAT) is the rate-limiting enzyme in the catabolism of polyamines. In the current study, the effect of increasing concentrations of apigenin on polyamine levels, ODC and SSAT protein expression, mRNA expression, cell proliferation and apoptosis, and the production of reactive oxygen species (ROS) was investigated in SW620 colon cancer cells. The results showed that apigenin significantly reduced cell proliferation, decreased the levels of spermidine and spermine, and increased previously downregulated putrescine contents. Apigenin also enhanced SSAT protein and mRNA levels and the production of reactive oxygen species in SW620 cells, though it had no significant effect on the levels of ODC protein or mRNA. Apigenin appears to decrease the proliferation rate of human SW620 cells by facilitating SSAT expression to induce polyamine catabolism and increasing ROS levels to induce cell apoptosis.

Absorption mechanism of oxymatrine in cultured Madin-Darby canine kidney cell monolayers.

Context Oxymatrine (OMT) is beneficial to human health by exerting various biological effects. Objective To investigate the absorption mechanism of OMT and discover absorption enhancers using Madin-Darby canine kidney (MDCK) cell monolayers. Materials and methods Concentration effects on the transport of OMT were measured in the range of 1.0 × 10(-5)-1.0 × 10(-3) M in 2 h. Then, the effect of time, direction, temperature and pH on the transport of OMT at 10(-4) M was studied. Moreover, Papp of OMT was determined in the absence/presence of cyclosporine and surfactants at 100 µM to further confirm the relative transport mechanism. Results The Papp AP→BL ranged from (3.040 ± 0.23) × 10(-6) to (3.697 ± 0.19) × 10(-6 )cm/s as the concentration varied from 10(-5) to 10(-3) M. OMT showed similar Papp at 4 and 37 °C (p > 0.05). Increasing the apical pH 7.4 and 8.0 resulted in Papp versus pH 5.0 (p < 0.01). Furthermore, in the presence of cyclosporine and surfactants including sodium citrate, sodium dodecyl sulphate (SDS) and deoxysodium cholate, Papp was (0.318 ± 0.033) × 10(-5), (0.464 ± 0.048) × 10(-5), (0.897 ± 0.115) × 10(-5) and (1.341 ± 0.122) × 10(-5 )cm/s, respectively. In the presence of surfactants, Papp significantly increased up to 1.5-4.3-fold (p < 0.05). Discussion and conclusion OMT transport across MDCK cell monolayers was by passive diffusion. Sodium citrate, SDS and deoxysodium cholate serve as excellent absorption enhancers which are useful for the related research improving the oral bioavailability of OMT.

Curcumol induces apoptosis in SPC-A-1 human lung adenocarcinoma cells and displays anti-neoplastic effects in tumor bearing mice.

Curcumol is a sesquiterpene originally isolated from curcuma rhizomes, a component of herbal remedies commonly used in oriental medicine. Its beneficial pharmacological activities have attract significant interest recently. In this study, anti-cancer activity of curcumol was examined with both in vitro and in vivo models. It was found that curcumol exhibited time- and concentration-dependent anti-proliferative effects in SPC-A-1 human lung adenocarcinoma cells with cell cycle arrest in the G0/G1 phase while apoptosis-induction was also confirmed with flow cytometry and morphological analyses. Interestingly, curcumol did not display growth inhibition in MRC-5 human embryonic lung fibroblasts, suggesting the anti-proliferative effects of curcumol were specific to cancer cells. Anti-neoplastic effects of curcumol were also confirmed in tumor bearing mice. Curcumol (60 mg/kg daily) significantly reduced tumor size without causing notable toxicity. In conclusion, curcumol appears a favorable anti-cancer candidate for further development.

Dodecanol-poly(D,L-lactic acid)-b-poly (ethylene glycol)-folate (Dol-PLA-PEG-FA) nanoparticles: evaluation of cell cytotoxicity and selecting capability in vitro.

Folate-conjugated Dol-poly(D,L-lactic acid)-b-poly (ethylene glycol)-folate (Dol-PLA-PEG-FA), was synthesized from dodecanol-poly(D,L-lactic acid), amino-terminated poly(ethylene glycol) and folate. (1)H NMR proved the successful synthesis of Dol-PLA-PEG-FA. Nanoparticles (NPs) were further fabricated from Dol-PLA-PEG-FA by using solvent evaporation-induced interfacial self-assembly method. The size, critical micelle concentration (CMC), cytotoxicity and selecting capability to cancer cells in vitro were examined for Dol-PLA-PEG-FA NPs. The size of NPs showed polymer concentration-dependent phenomenon in the fabrication process, and its polydispersity index (PDI) was very narrow. The CMC was determined as 1.995×10(-4) g/L in aqueous solution, which is much lower than the reported CMC of block copolymer self-assemble micelles. The cytotoxicity evaluation revealed that the obtained NPs2 are non-toxic to either breast cancer cell or normal endothelial cells, and the cell uptake of NPs indicated that the NPs demonstrated much higher selecting capability to breast cancer cells compared to normal fibroblast cells. The possible receptor-mediated endocytosis pathway mechanism was proposed. Based on the above results, it could be concluded that Dol-PLA-PEG-FA polymer and its nanoparticles can be potentially used as a safe drug carrier with strong tumor cells targeting capability for tumor chemotherapy.

A novel CD105 determination system based on an ultrasensitive bioelectrochemical strategy with Pt nanoparticles.

CD105 is a well-known tumor metastasis marker and useful for early monitoring of metastasis and cancer relapse. It is important to generate rapid, reliable and precise analytical information regarding CD105 levels. To establish a simple, selective and sensitive detection method, we prepared an immunosensor with novel bioconjugates based on Pt nanoparticles, thionin acetate and antibodies. The proposed immunosensor displayed a broader linear response to CD105, with a working range of 1.3 to 200.0 ng/mL and a detection limit of 0.9 ng/mL under optimal conditions. Moreover, the studied immunosensor exhibited high sensitivity, fast analysis and adequate stability. The proposed methodology could readily be extended to other clinical- or environment-related biospecies.

Plasmid-borne catabolism of methyl parathion and p-nitrophenol in Pseudomonas sp. strain WBC-3.

Pseudomonas sp. strain WBC-3 utilises methyl parathion (MP) or p-nitrophenol (PNP) as the sole source of carbon, nitrogen, and energy. A plasmid designated pZWL0 of approximately 70 kb in this strain was found to be responsible for MP and PNP degradation. This was based on the fact that the plasmid-cured strains showed PNP- MP- phenotype and the PNP+ MP+ phenotype could be conjugally transferred. We have also cloned a 3.4-kb HindIII fragment which exhibited methyl parathion hydrolase activity, which revealed a methyl parathion hydrolase (mph) gene whose DNA sequence is 99.5% identical to the recently identified mpd gene from Plesiomonas sp. M6 [C. Zhongli, L. Shunpeng, F. Guoping, Isolation of methyl parathion-degrading strain M6 and cloning of the methyl parathion hydrolase gene, Appl. Environ. Microbiol. 67 (2001) 4922-4925]. The mph gene was functionally expressed in Escherichia coli and the relative activities of the enzyme against different substrates were determined. The sequence alignment and phylogenetic analysis suggested that MPH and MPD evolved independently from other well-studied organophosphate hydrolases and may be originated from class B beta-lactamase family. Subsequently obtained a 6.5-kb KpnI and BamHI fragment containing the above HindIII fragment revealed that the mph gene was physically located in a typical transposon.

[Study of HLA molecules and its associated genes expression in human ovarian cancer cells].

AIM: To explore the correlation between the expressions of HLA gene and its related gene, and expression of class II transactivator (CIITA) gene induced by IFN-gamma in human ovarian cells. METHODS: The expression of HLA molecule in the tumor cells was detected by Western blot, immunohistochemical staining and flow cytometry. The expressions of transporters associated with antigen processing (TAP), low molecular weight peptides (LMP), and CIITA genes were analyzed by RT-PCR. RESULTS: Abnormal expression rate of HLA class I molecule reached 45% in the 11 ovarian cancer cells. The expressed abnormalities of HLA class I molecule had relation to those of 4 genes (TAP1, TAP2, LMP2 and LMP7). Expression of HLA class II molecule was identical with that of CIITA gene in the ovarian cancer cells or other tumor cells. After IFN-gamma treatment, expressions of HLA class I and II molecule were increased in the cells of CIITA-expressing constitutively or inducibly, while no enhancement of HLA molecule expression manifested itself in the tumor cells of that CIITA was not yet expressed after IFN-gamma induction. CONCLUSION: Deletion of TAP and LMP gene expression in the ovarian cancer cells is an important factor causing abnormal expression of HLA class I molecule, suggesting that the CIITA gene has involved in the modulation of HLA classes I and II molecule expressions in the tumor cells.

Cytotoxic ent-kaurane diterpenoids from Isodon sculponeata.

Four new ent-kaurane diterpenoids, sculponeatins F-I (1-4), together with six known compounds, sculponeatin E (5), epi-nodosin (6), epi-nodosinol (7), enmein (8), and macrocalyxoformins A and B (9 and 10), were isolated from the leaves of Isodon sculponeata. Also obtained were ursolic acid, 2alpha,3beta-dihydroxy-urs-12-en-28-oic acid, 2alpha,3beta,19alpha-trihydroxy-urs-12-en-28-oic acid, beta-sitosterol, daucosterol, quercetin, pedalitin, rosmarinic acid, caffeic acid and ethyl caffeic acid. Their structures were determined by spectral methods (1D-, 2D-NMR and MS). Some diterpenoids were tested for their cytotoxicity to inhibit three kinds of human tumor cells K562, A549 and T24. Compounds 3, 4, 6, 8, and 10 showed significant inhibitory effect toward K562 with IC(50) values ranging from 3.2 microg/ml to 8.2 microg/ml, while 3 and 6 exhibited potent antitumor activity against T24, but none exhibited cytotoxicity toward the cells of A549.

Diterpenoids from Isodon adenantha.

Eleven new diterpenoids, adenanthins B-L (1-11), together with five known analogues, calcicolin B (12), adenanthin (13), weisiensin A (14), nervosanin (15), and forrestin C (16), were isolated from the aerial parts of Isodon adenantha. The structures of 1-11 were elucidated on the basis of spectral methods, as well as the X-ray crystallographic analysis of 11. Compounds 2, 5, and 14 showed significant inhibitory activities against K562 cells, with IC(50) values less than 4.0 microg/mL, respectively.

Cytotoxic ent-kaurane diterpenoids from Isodon eriocalyx var. laxiflora.

Three new ent-kaurane diterpenoids laxiflorin E (1), laxiflorin H (6) and laxiflorin I (8) were isolated from the leaves of Isodon eriocalyx var. laxiflora, along with nine known diterpenoids, eriocalyxin A (2), laxiflorin C (3), laxiflorin D (4), laxiflorin A (5), maoecrystal S (7), maoecrystal Q (9), eriocalyxin B (10), maoecrystal C (11) and enmelol (12). The structures of the new compounds were determined by spectroscopic methods. Compounds 1-5 are 6,7-seco-ent-kaurane-7,20-olide diterpenoids, and 6-12 belong to 7,20-epoxy-ent-kauranoids. The spectral data of enmelol (12) are reported here for the first time. Ten of these compounds were tested for their cytotoxicity toward K562 and T24 human tumor cells. Compounds 1, 3 and 10 showed significant inhibitory effects on K562 cells with IC50 values 0.077, 0.569 and 0.373 microg/mL, and compounds 1 and 10 also demonstrated significant inhibitory activities toward T24 cells with IC50 values 0.709 and 0.087 microg/mL. Compounds 8 and 11 also displayed inhibitory effect on both two kinds of cells with IC 50 value less than 6.5 microg/mL.