AIM: To develop a fuzzy classification method to score the texture features of pancreatic cancer in endoscopic ultrasonography (EUS) images and evaluate its utility in making prognosis judgments for patients with unresectable pancreatic cancer treated by EUS-guided interstitial brachytherapy.
METHODS: EUS images from our retrospective database were analyzed. The regions of interest were drawn, and texture features were extracted, selected, and scored with a fuzzy classification method using a C++ program. Then, patients with unresectable pancreatic cancer were enrolled to receive EUS-guided iodine 125 radioactive seed implantation. Their fuzzy classification scores, tumor volumes, and carbohydrate antigen 199 (CA199) levels before and after the brachytherapy were recorded. The association between the changes in these parameters and overall survival was analyzed statistically.
RESULTS: EUS images of 153 patients with pancreatic cancer and 63 non-cancer patients were analyzed. A total of 25 consecutive patients were enrolled, and they tolerated the brachytherapy well without any complications. There was a correlation between the change in the fuzzy classification score and overall survival (Spearman test, r = 0.616, P = 0.001), whereas no correlation was found to be significant between the change in tumor volume (P = 0.663), CA199 level (P = 0.659), and overall survival. There were 15 patients with a decrease in their fuzzy classification score after brachytherapy, whereas the fuzzy classification score increased in another 10 patients. There was a significant difference in overall survival between the two groups (67 d vs 151 d, P = 0.001), but not in the change of tumor volume and CA199 level.
CONCLUSION: Using the fuzzy classification method to analyze EUS images of pancreatic cancer is feasible, and the method can be used to make prognosis judgments for patients with unresectable pancreatic cancer treated by interstitial brachytherapy.
Digital image processing; Fuzzy classification; Endoscopic ultrasonography; Pancreatic cancer; Interstitial brachytherapy; Prognosis
The accuracy of the diagnosis is vital when administrative databases are used for pharmacoepidemiologic and outcome studies. Data pertaining to the utility of databases for rheumatoid arthritis (RA) is sparse and variable. We assessed the utility of various diagnostic algorithms to identify RA patients within the Veterans Health Administration (VHA) databases.
Using the ICD code for RA at two visits, at least six months apart, we identified 1779 patients between 10/1/1998 and 9/30/2009 in our local Veteran Affairs Medical Center administrative database. Disease Modifying Anti Rheumatic Drugs (DMARD) use was ascertained from the pharmacy database. Cases were analyzed based on DMARD therapy and RA codes at clinic visits. 543 patients' medical records selected by stratification and random selection on the basis of their visits were reviewed to ascertain the clinicians' diagnoses and clinical criteria documentation. Positive predictive values (PPV) were calculated for various database case identification algorithms using diagnosis of RA by medical record review as the gold standard.
PPV for identification of RA with two RA codes six months apart was 30.9%. Addition of DMARD therapy increased the PPV to 60.4%. The PPV further increased to 91.4% when having RA code at the last VAMC rheumatology clinic visit criterion was added.
An algorithm using only two administrative RA codes six months apart had a low PPV for correctly identifying patients with RA in the VHA database. Including DMARD therapy and requiring a RA code at the last visit with a rheumatologist increased the performance of the data extraction algorithm.
Rheumatoid Arthritis; Health Services Research; Computerized records; Databases; ICD codes
Aggregatibacteractinomycetemcomitansis a gram-negative facultative capnophile involved in pathogenesis of aggressive forms of periodontal disease. In the present study, we interrogated the ability of A. actinomycetemcomitans to stimulate innate immune signaling and cytokine production then established that A.actinomycetemcomitans causes bone loss in a novel rat calvarial model. In vitro studies indicated that A. actinomycetemcomitansstimulated considerable production of soluble cytokines, TNF-α, IL-6, and IL-10 in both primary bone marrow derived macrophages and NR8383 macrophages. Immunoblot analysis indicated that A. actinomycetemcomitansexhibits sustained activation of all major mitogen activated protein kinase (MAPK) pathways, as well as the negative regulator of MAPK signaling, MAPK phosphatase-1 (MKP-1),for at least 8 hours. In a rat calvarial model of inflammatory bone loss, high and low doses of formalin fixed A. actinomycetemcomitanswere microinjected into the supraperiostealcalvarial space for 1 to 2 weeks.Histological staining and micro-computed tomography (μCT) of rat calvariae revealed a significant increase of inflammatoryand fibroblast infiltrate and increased bone resorptionas measured by total lacunar pit formation.From these data, we provide new evidence thatfixed whole cell A. actinomycetemcomitansstimulation elicits a pro-inflammatory host response through sustained MAPK signaling leading to enhanced bone resorption within the rat calvarial bone.
periodontal disease; host immune response; cytokines; bone loss
AIM: To provide long-term survival results of operable duodenal gastrointestinal stromal tumors (DGISTs) in a tertiary center in China.
METHODS: In this retrospective study, the pathological data of 28 patients with DGISTs who had been treated surgically at the Second Department of General Surgery, Sir Run Run Shaw Hospital (SRRSH) from June 1998 to December 2006 were reviewed. All pathological slides were examined by a single pathologist to confirm the diagnosis. In patients whose diagnosis was not confirmed by immunohistochemistry at the time of resection, representative paraffin blocks were reassembled, and sections were studied using antibodies against CD117 (c-kit), CD34, smooth muscle actin (SMA), vimentin, S-100, actin (HHF35), and desmin. Operative procedures were classified as wedge resection (WR, local resection with pure closure, without duodenal transection or anastomosis), segmental resection [SR, duodenal transection with Roux-Y or Billroth II gastrojejunostomy (G-J), end-to-end duodenoduodenostomy (D-D), end-to-end or end-to-side duodenojejunostomy (D-J)], and pancreaticoduodenectomy (PD, Whipple operation with pancreatojejunostomy). R0 resection was pursued in all cases, and at least R1 resection was achieved. Regional lymphadenectomy was not performed. Clinical manifestations, surgery, medical treatment and follow-up data were retrospectively analyzed. Related studies in the literature were reviewed.
RESULTS: There were 12 males and 16 females patients, with a median age of 53 years (20-76 years). Their major complaints were “gastrointestinal bleeding” (57.2%) and “nonspecific discomfort” (32.1%). About 14.3%, 60.7%, 17.9%, and 7.1% of the tumors originated in the first to fourth portion, respectively, with a median size of 5.8 cm (1.6-20 cm). Treatment was by WR in 5 cases (17.9%), SR in 13 cases (46.4%), and by PD in 10 cases (35.7%). The morbidity and mortality rates were 35.7% and 3.6%, respectively. The median post-operative stay was 14.5 d (5-47 d). During a follow-up of 61 (23-164) mo, the 2-year and 5-year relapse-free survival was 83.3% and 50%, respectively. Eighty-four related articles were reviewed.
CONCLUSION: Surgeons can choose to perform limited resection or PD for operable DGISTs if clear surgical margins are achieved. Comprehensive treatment is necessary.
Gastrointestinal stromal tumors; Duodenum; Limited resection; Pancreaticoduodenectomy; Survival
The association between type 2 diabetes and low testosterone has been well recognized. However, testosterone levels in men with prediabetes have been rarely reported. We aimed to investigate whether prediabetes was associated with an increased risk of testosterone deficiency.
This study included 1,306 men whose sex hormones was measured during a medical examination. Serum total testosterone and sex hormone-binding globulin were measured; free and bioavailable testosterone concentrations were calculated by Vermeulen’s formula. Prediabetes was defined by impaired fasting glucose (IFG), impaired postprandial glucose (IPG), or glycated hemoglobin (HbA1c) 5.7%-6.4%. Logistic regression was performed to obtain the odds ratios (OR) for subnormal total testosterone (<300 ng/dL) or free testosterone (<6 ng/dL) in prediabetic and diabetic men compared with normoglycemic individuals, while adjusting for age, BMI, waist circumference, and metabolic syndrome (MetS).
Normoglycemia, prediabetes, and diabetes were diagnosed in 577 (44.2%), 543 (41.6%), and 186 (14.2%) men, respectively. Prediabetes was associated with an increased risk of subnormal total testosterone compared to normoglycemic individuals (age-adjusted OR=1.87; 95%CI=1.38-2.54). The risk remained significant in all multivariate analyses. After adjusting for MetS, the OR in prediabetic men equals that of diabetic patients (1.49 versus 1.50). IFG, IPG, and HbA1c 5.7%-6.4% were all associated with an increased risk of testosterone deficiency, with different levels of significance in multivariate analyses. However, neither prediabetes nor diabetes was associated with subnormal free testosterone in multivariate analyses.
Prediabetes is associated with an increased risk of testosterone deficiency, independent of obesity and MetS. After adjusting for MetS, the risk equals that of diabetes. Our data suggest that testosterone should be measured routinely in men with prediabetes.
In the title complex, [Cu(C9H4O6)(H2O)3]n, the CuII cation exhibits a distorted square-pyramidal coordination geometry involving five O atoms from two monodentate 5-carboxybenzene-1,3-dicarboxylate anions and three water molecules. The 5-carboxybenzene-1,3-dicarboxylate anions bridge CuII cations into zigzag polymeric chains running along the b-axis direction. These chains are further linked by O—H⋯O hydrogen bonds between coordinating water molecules or carboxyl groups and carboxylate groups into a three-dimensional supramolecular architecture. In the crystal, π–π stacking is observed between parallel benzene rings of adjacent chains, the centroid–centroid distances being 3.584 (3) and 3.684 (3) Å.
Relation extraction in biomedical text mining systems has largely focused on identifying clause-level relations, but increasing sophistication demands the recognition of relations at discourse level. A first step in identifying discourse relations involves the detection of discourse connectives: words or phrases used in text to express discourse relations. In this study supervised machine-learning approaches were developed and evaluated for automatically identifying discourse connectives in biomedical text.
Materials and Methods
Two supervised machine-learning models (support vector machines and conditional random fields) were explored for identifying discourse connectives in biomedical literature. In-domain supervised machine-learning classifiers were trained on the Biomedical Discourse Relation Bank, an annotated corpus of discourse relations over 24 full-text biomedical articles (∼112 000 word tokens), a subset of the GENIA corpus. Novel domain adaptation techniques were also explored to leverage the larger open-domain Penn Discourse Treebank (∼1 million word tokens). The models were evaluated using the standard evaluation metrics of precision, recall and F1 scores.
Results and Conclusion
Supervised machine-learning approaches can automatically identify discourse connectives in biomedical text, and the novel domain adaptation techniques yielded the best performance: 0.761 F1 score. A demonstration version of the fully implemented classifier BioConn is available at: http://bioconn.askhermes.org.
Analysis; automated learning; controlled terminologies and vocabularies; discovery; display; image representation; knowledge acquisition and knowledge management; knowledge bases; knowledge representations; machine learning; natural language processing; NLP; ontologies; processing; text and data mining methods
Bone marrow-derived endothelial progenitor cells (EPCs) constitute an important endogenous system in the maintenance of endothelial integrity and vascular homeostasis. Cardiovascular risk factors are associated with a reduced number and functional capacity of EPCs. Here we investigated the effect of transplantation of bone marrow-derived cells from Dahl salt-resistant rat into age-matched Dahl salt-sensitive (DS) rat on blood pressure, endothelial function, and circulating EPC number. The recipient DS rats were fed a normal (0.5% NaCl, NS) or high salt (4% NaCl, HS) diet for 6 weeks after BMT. DS rats on a NS or a HS diet without BMT were used as controls. Hypertensive DS (HS-DS) rat (systolic blood pressure: 213 ± 4 mmHg vs. 152 ± 4 mmHg in NS, p<0.05) manifested impaired endothelium-dependent relaxation to acetylcholine (EDR), increased gene expression of vascular oxidative stress and proinflamamtory cytokines, and decreased eNOS expression. BMT on HS-DS rat significantly improved EDR and eNOS expression, reduced oxidative stress without reduction in SBP (206 ± 6 mmHg). Flow cytometry analysis showed that there was no difference in the number of circulating EPCs, demonstrated by expression of EPC markers CD34, cKit, and vascular endothelial growth factor, between hypertensive and normotensive rats. Surprisingly, BMT resulted in a 5–10 fold increase in the above-mentioned EPC markers in hypertensive, but not normotensive rat. These results suggest that DS rat has an impaired ability to increase bone marrow-derived EPCs in response to HS diet challenge, which may contribute to endothelial dysfunction.
Bone marrow transplantation; Endothelial progenitor cells; Endothelial function; Salt-sensitive hypertension
Immune-related pancytopenia (IRP) is one kind of bone marrow failure diseases which is related to autoantibodies. Autoantibodies have been detected on the membrane of various bone marrow (BM) hemopoietic cells by BM mononuclear-cell-Coombs test or flow cytometric analysis. There are autoantibodies in the BM supernatant of IRP patients, which can target several antigens on hematopoietic cells membranes by western blot. T follicular helper (Tfh) cells are the true helper cells for Ab responses, which represent one of the most numerous and important subsets of effector T cells. Dysregulation of Tfh cell function or expression of Tfh cell-associated molecules could contribute to the pathogenesis of autoimmune diseases. Currently, there are no studies regarding the role of Tfh cells in IRP patients. The percentages of Tfh cells, Tfh-related molecules ICOS, CD40L, IL-21, and Bcl-6 in BM were investigated in 90 patients with IRP, and 25 healthy controls. We observed that there exist increased quantity and hyperfunction of Tfh cells in IRP, and the results were correlated with patient characteristics. It was indicated that dysregulated Tfh cells might be involved in the pathogenesis of IRP and that inhibition of Tfh cells effector molecules might provide opportunities for new therapeutic approaches to IRP and even other human autoimmune diseases.
Nimotuzumab is a humanized IgG1 monoclonal antibody specifically targeting EGFR. In this study, we aimed to investigate the molecular mechanisms of nimotuzumab in its effects of enhancing cancer cell radiosensitivity.
Lung cancer A549 cells and breast cancer MCF-7 cells were pretreated with or without nimotuzumab for 24 h before radiation to perform the clonogenic survival assay and to analyze the cell apoptosis by flow ctyometry. γ-H2AX foci were detected by confocal microscopy to assess the effect of nimotuzumab on radiation induced DNA repair. EGFR activation was examined and the levels of DNA damage repair related proteins in A549 cells at different time point and at varying doses exposure after nimotuzumab and radiation treatment were examined by Western blot. Pretreatment with nimotuzumab reduced clonogenic survival after radiation, inhibited radiation-induced EGFR activation and increased the radiation-induced apoptosis in both A549 cells and MCF-7 cells. The foci of γ-H2AX 24 h after radiation significantly increased in nimotuzumab pretreated cells with different doses. The phosphorylation of AKT and DNA-PKcs were remarkably inhibited in the combination group at each dose point as well as time point.
Our results revealed that the possible mechanism of nimotuzumab enhancing the cancer radiosensitivity is that nimotuzumab inhibited the radiation-induced activation of DNA-PKcs through blocking the PI3K/AKT pathway, which ultimately affected the DNA DSBs repair.
Mitogen Activating Protein (MAPK) kinase phosphatase-1 (MKP-1) has been shown to be a key negative regulator of the MAP kinase pathways of the innate immune system. The impact of MKP-1 in an endodontic model has yet to be studied. Thus, the purpose of this study was to determine the role of MKP-1 in a bacterial-driven model of pathological endodontic bone loss.
Pulps were exposed in both lower 1st molars of 10-week old mkp-1+/+ and mkp-1−/− mice and left open to the oral environment for either 3 or 8 weeks. At sacrifice, mandibles were harvested and scanned by microcomputed tomography (μCT) to determine periapical bone loss. Histopathological scoring was then performed on the samples to determine the amount of inflammatory infiltrate within the periapical microenvironment.
Significant bone loss and inflammatory infiltrate were found in all experimental groups when compared to control. No statistical difference was found between mkp-1+/+ and mkp-1−/− at either time point with respect to bone loss or inflammatory infiltrate. At 8 weeks, male mkp-1−/− mice were found to have significantly more bone loss and inflammatory infiltrate when compared to female mkp-1−/− mice. There was also a significant correlation between an increase in bone loss and increase in inflammatory infiltrate.
A sexual dimorphism exists in the periapical inflammatory process, where male mkp-1−/− mice have more inflammation than female mkp-1−/− mice. The increase in inflammatory infiltrate correlates to more bone loss in the male mice.
MAP kinase phophatase-1; sexual dimorphism; periapical bone loss; inflammation
The unabated circulation of the highly pathogenic avian influenza A virus/H5N1 continues to be a serious threat to public health worldwide. Because of the high frequency of naturally occurring mutations, the emergence of H5N1 variants with high virulence has raised great concerns about the potential transmissibility of the virus in humans. Recent studies have shown that laboratory-mutated or reassortant H5N1 viruses could be efficiently transmitted among mammals, particularly ferrets, the best animal model for humans. Thus, it is critical to establish effective strategies to combat future H5N1 pandemics. In this study, we identified a broadly neutralizing monoclonal antibody (MAb), HA-7, that potently neutralized all tested strains of H5N1 covering clades 0, 1, 2.2, 2.3.4, and 184.108.40.206 and completely protected mice against lethal challenges of H5N1 viruses from clades 1 and 2.3.4. HA-7 specifically targeted the globular head of the H5N1 virus hemagglutinin (HA). Using electron microscopy technology with three-dimensional reconstruction (3D-EM), we discovered that HA-7 bound to a novel and highly conserved conformational epitope that was centered on residues 81 to 83 and 117 to 122 of HA1 (H5 numbering). We further demonstrated that HA-7 inhibited viral entry during postattachment events but not at the receptor-binding step, which is fully consistent with the 3D-EM result. Taken together, we propose that HA-7 could be humanized as an effective passive immunotherapeutic agent for antiviral stockpiling for future influenza pandemics caused by emerging unpredictable H5N1 strains. Our study also provides a sound foundation for the rational design of vaccines capable of inducing broad-spectrum immunity against H5N1.
Nutritional evaluation is important for patients with esophageal cancer, but the impact of undernutrition on outcome of those patients is not well elucidated. Our aim is to assess the impact of baseline nutritional status on overall survival (OS) in Chinese patients with esophageal squamous cell carcinoma (ESCC) and to detect a most appropriate indicator for nutritional evaluation.
502 patients from Southern China diagnosed as ESCC in Sun Yat-Sen University Cancer Center were included. A series of nutritional indicators were introduced to evaluate the baseline nutritional status. Kaplan-Meier method was used to estimate the 5-year OS and the log-rank test was used to determine the survival differences. Cox proportional hazards model was used in the univariate and multivariate analyses of OS.
With a median follow up time of 30 months, the median OS for the entire patient group was 37.3 months with the 5-year OS rate of 43.0%. Only performance status, AJCC 6th stage and body mass index (BMI) were the independent prognostic factors in multivariate analysis of OS. The median OS for patients with BMI less than 18.5, patients with BMI within 18.5-24.9 and patients with BMI more than 24.9 were 19.2, 43.2 and 51.6 months, respectively, with the 5-year OS rates of 25.2%, 46.1% and 48.1% (P<0.001). Patients with BMI <18.5 tended to present with a more advanced stage disease and a poorer tumor grade.
Baseline nutritional status is predictive of OS in Chinese patients with ESCC. BMI is a steady indicator for nutritional evaluation and a sensitive prognostic parameter for ESCC patients. Treatment optimization in ESCC patients with low BMI should integrate the modalities and individual nutritional support.
Nutritional parameters; body mass index (BMI); prognostic value; esophageal squamous cell carcinoma
Enhancing ion and electron transport kinetics together with improving cycle life are important issues to be considered when developing high-performance Li ion batteries. Here we demonstrate a three dimensional ordered macroporous conductive electrode concept by entrapping electrode active nanoparticles in an interpenetrating macroporous carbon inverse opal. The electrodes are featured with simultaneously enhanced ion and electron transport kinetics as well as geometrically constrained active nanoparticles. The electrode can deliver up to 94.17% of theoretical capacity over 1000 discharge/charge cycles at a current density of 2.0 A g−1, and exhibits good rate capability in the high current density range of 1.0–10.0 A g−1. We hope that our findings will help pave the way for tailored design of many other sophisticated electrode materials in electrochemistry.
Paraoxonase-1 (PON1), a high-density-lipoprotein- (HDL-) associated enzyme, has the potential to protect against atherogenesis. We examine the relationships between plasma PON1 activity and the progression of atherosclerosis as well as coronary artery disease (CAD). Fasting blood samples were collected from female apolipoprotein E-deficient (apoE−/−) mice and 149 patients undergoing coronary angiography for the biochemical parameters measurement. The severity of CAD was defined using angiographic Gensini score (GSS). Compared to 3-month-old apoE−/− mice, aged mice had significantly lower PON1 activity, which is negatively correlated with the size of atherosclerotic lesion and plasma interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) levels. In study patients, PON1 activity was correlated with age, sex, and HDL-cholesterol, apolipoprotein AI, and high-sensitivity C-reactive protein (hs-CRP) levels and was significantly lower in CAD group than that in non-CAD control group. Interestingly, PON1 activity in severe CAD group (GSS > 40) was further significantly reduced compared to those in mild and moderate subgroups (GSS ≤ 40) (P < 0.01). There is a significant correlation between PON1 activity and the severity of CAD as assessed by GSS (r = −0.393, P < 0.001). PON1 activity may be a potential biomarker for the severity of CAD.
In the field of catalysis, it is highly desired to develop novel catalysts that combine the advantages of both homogeneous and heterogeneous catalysts. Here we disclose that the use of plant pholyphenol as amphiphilic large molecule ligand/stabilizer allows for the preparation of noble metal complex and noble metal nanoparticle catalysts. These catalysts are found to be highly selective and active in aqueous-organic biphasic catalysis of cinnamaldehyde and quinoline, and can be reused at least 3 times without significant loss of activity. Moreover, the catalytic activity and reusability of the catalysts can be rationally controlled by simply adjusting the content of polyphenols in the catalysts. Our strategy may be extended to design a wide range of aqueous-organic biphasic catalysis system.
Kawasaki disease (KD) is an acute febrile vasculitic syndrome of early childhood often complicated by coronary artery lesion that drastically reduces the quality of life. The study aimed to identify a reliable marker for predicting nonresponsiveness to the first course of intravenous immunoglobulin (IVIG) in KD patients. A total of 63 patients with KD were enrolled in the study (IVIG response, 58; IVIG resistance, 5). Plasma samples were collected before and after IVIG infusion for measurement of biomarkers. Patients' clinical characteristics and laboratory data were also analyzed. A receiver operating characteristic curve was generated to identify a cut-off value for predicting IVIG resistance. Among the biomarkers, the difference in plasma clusterin concentrations before and after IVIG infusion (CLUSTER 12) was significantly related to IVIG resistance (P = 0.040; 95% confidence interval (CI): −25.8% to −6.0%). Using a CLUSTER 12 cut-off value of <8.52 mg/L, the odds ratio for IVIG resistance was 11.467 (95% CI: 1.186 to 110.853). Patients with plasma CLUSTER 12 concentrations >8.52 mg/L had a much higher risk of IVIG resistance than those with CLUSTER 12 concentrations <8.52 mg/L. Plasma clusterin concentration shows promise as a candidate biomarker for predicting IVIG resistance in patients with KD.
Leukocyte cell–derived chemotaxin 2 enhances phagocytosis and bacterial killing of macrophages to improve the outcome of bacterial-induced sepsis.
Leukocyte cell–derived chemotaxin 2 (LECT2) is a multifunctional cytokine and reduced plasma levels were found in patients with sepsis. However, precise functions and mechanisms of LECT2 remain unclear. The aim of the present study was to determine the role of LECT2 in modulating immune responses using mouse sepsis models. We found that LECT2 treatment improved outcome in mice with bacterial sepsis. Macrophages (MΦ), but not polymorphonuclear neutrophils, mediated the beneficial effect of LECT2 on bacterial sepsis. LECT2 treatment could alter gene expression and enhance phagocytosis and bacterial killing of MΦ in vitro. CD209a was identified to specifically interact with LECT2 and mediate LECT2-induced MΦ activation. CD209a-expressing MΦ was further confirmed to mediate the effect of LECT2 on sepsis in vivo. Our data demonstrate that LECT2 improves protective immunity in bacterial sepsis, possibly as a result of enhanced MΦ functions via the CD209a receptor. The modulation of MΦ functions by LECT2 may serve as a novel potential treatment for sepsis.
The Wnt signaling pathway plays an essential role in tumor invasion and migration. DKK1 functions as an important inhibitor of the pathway and represents a promising target for cancer therapy. The aim of the present study was to determine the role of DKK1 in endometrial carcinoma (EC) cell invasion and migration using RNA interference (RNAi) technology. Ishikawa EC cells were transfected at high efficiency with specific DKK1 siRNA. RT-PCR and western blot analysis were used to determine the mRNA and protein levels of DKK1, β-catenin and metalloproteinase 14 (MMP14) in siRNA-treated and -untreated cells. In addition, the invasion and migration of the EC cells were detected by invasion and migration assays. Transient transfection of DKK1 siRNA significantly inhibited the mRNA and protein levels of DKK1. Markedly increased cell invasion and migration was observed following treatment with DKK1 siRNA when compared with the negative control siRNA-treated and siRNA-untreated cells. The knockdown of DKK1 also elevated the mRNA and protein levels of β-catenin and MMP14 involved in the Wnt signaling pathway, indicating that targeting this gene may promote intracellular Wnt signal transduction and thus, accelerate EC cell invasion and migration in vitro. The RNAi-mediated targeting of DKK1 gene expression in Ishikawa EC cells resulted in increased tumor cell invasion and migration. DKK1 was identified as an inhibitor of EC cell invasion and migration via its novel role in the Wnt signaling pathway. Targeting DKK1 may therefore represent an effective anti-invasion and -migration strategy for the treatment of EC.
β-catenin; DKK1; endometrial carcinoma; invasion; migration; MMP14; RNAi
Antibody mediated allograft rejection is an increasingly recognized problem in clinical transplantation. However, the primary location of donor specific alloantibody (DSA) producing cells after transplantation have not been identified. The purpose of this study was to test the contribution of allospecific antibody secreting cells (ASCs) from different anatomical compartments in a mouse transplantation model. Fully MHC-mismatched heart allografts were transplanted into three groups of recipients: non-sensitized wild type, alloantigen-sensitized wild type and CCR5−/− mice that have exaggerated alloantibody responses. We found that previous sensitization to donor alloantigens resulted in the development of anti-donor alloantibody (alloAb) with accelerated kinetics. Nevertheless, the numbers of alloantibody secreting cells and the serum titers of anti-donor IgG alloantibody were equivalent in sensitized and non-sensitized recipients six weeks after transplantation. Regardless of recipient sensitization status, the spleen contained higher numbers of donor-reactive ASCs than bone marrow at days 7–21 after transplantation. Furthermore, individual spleen ASCs produced more anti-donor IgG alloantibody than bone marrow ASCs. Taken together, our results indicate that the spleen rather than bone marrow is the major source of donor-reactive alloAb early after transplantation in both sensitized and non-sensitized recipients.
alloantibody; plasma cells; sensitization; spleen; bone marrow
Salvia splendens Ker-Gawl, most commonly used in China to add a splash of brilliant color to the surroundings during the warm season, is subject to heat stress, which can greatly affect its growth and yield.
To gain a comprehensive understanding of heat-tolerance mechanisms of S. splendens, we assessed the heat-stress responses and characterized the proteomes of leaves from two varieties, Vista (heat resistant) and King (heat sensitive). Denaturing two-dimensional gel electrophoresis (2–DE) and tandem mass spectrometry were used to identify heat-responsive proteins. Heat stress induced the reversible inactivation of photosystem II reaction centers and increased the amounts of antioxidative enzymes, thereby decreasing oxidative damage. Vista leaves had a much greater ability than King leaves to develop light-protective and oxygen-scavenging systems in response to heat stress. More than 1213 leaf proteome spots were reproducibly detected in the gels, with a total of 33 proteins in each leaf type differentially regulated when Salvia splendens were heat stress treated. Of these proteins, 23 and 28 from Vista and King, respectively, were identified.
Most of the identified proteins are involved in photosynthesis, metabolism, protein processing, or stress response, indicating that many different processes work together to establish a new cellular homeostasis in response to heat stress.
Enteral nutrition is increasingly advocated in the treatment of acute pancreatitis, but its timing is still controversial. The aim of this meta-analysis was to find out the feasibility of early enteral nutrition within 48 hours of admission and its possible advantages.
Methods and Findings
We searched PubMed, EMBASE Databases, Web of Science, the Cochrane library, and scholar.google.com for all the relevant articles about the effect of enteral nutrition initiated within 48 hours of admission on the clinical outcomes of acute pancreatitis from inception to December 2012. Eleven studies containing 775 patients with acute pancreatitis were analyzed. Results from a pooled analysis of all the studies demonstrated that early enteral nutrition was associated with significant reductions in all the infections as a whole (OR 0.38; 95%CI 0.21–0.68, P<0.05), in catheter-related septic complications (OR 0.26; 95%CI 0.11–0.58, P<0.05), in pancreatic infection (OR 0.49; 95%CI 0.31–0.78, P<0.05), in hyperglycemia (OR 0.24; 95%CI 0.11–0.52, P<0.05), in the length of hospitalization (mean difference −2.18; 95%CI −3.48−(−0.87); P<0.05), and in mortality (OR 0.31; 95%CI 0.14–0.71, P<0.05), but no difference was found in pulmonary complications (P>0.05). The stratified analysis based on the severity of disease revealed that, even in predicted severe or severe acute pancreatitis patients, early enteral nutrition still showed a protective power against all the infection complications as a whole, catheter-related septic complications, pancreatic infection complications, and organ failure that was only reported in the severe attack of the disease (all P<0.05).
Enteral nutrition within 48 hours of admission is feasible and improves the clinical outcomes in acute pancreatitis as well as in predicted severe or severe acute pancreatitis by reducing complications.
Recent clinical reports have indicated that myocardial bridge and mural coronary artery complex (MB-MCA) might cause major adverse cardiac events. 256-slice CT angiography (256-slice CTA) is a newly developed CT system with faster scanning and lower radiation dose compared with other CT systems. The objective of this study is to evaluate the morphological features of MB-MCA and determine its changes from diastole to systole phase using 256-slice CTA. The imaging data of 2462 patients were collected retrospectively. Two independent radiologists reviewed the collected images and the diagnosis of MB-MCA was confirmed when consistency was obtained. The length, diameter, and thickness of MB-MCA in diastole and systole phases were recorded, and changes of MB-MCA were calculated. Our results showed that among the 2462 patients examined, 336 have one or multiple MB-MCA (13.6%). Out of 389 MB-MCA segments, 235 sites were located in LAD2 (60.41%). The average diameter change of MCA in LAD2 from systole phase to diastole phase was 1.1 ± 0.4 mm, and 34.9% of MCA have more than 50% diameter stenosis in systole phase. This study suggested that 256-slice CTA multiple-phase reconstruction technique is a reliable method to determine the changes of MB-MCA from diastole to systole phase.
Derivatives of 4-hydroxyproline with a series of hydrophobic groups in well-defined orientations have been tested as catalysts for the aldol reactions. All of the modified proline catalysts carry out the intermolecular aldol reaction in water and provide high diastereoselectivity and enantioselectivity. Modified prolines with aromatic groups syn to the carboxylic acid are better catalysts than those with small hydrophobic groups (1a is 43.5 times faster than 1f). Quantum mechanical calculations provide transition structures, TS-1awater and TS-1fwater that support the hypothesis that a stabilizing hydrophobic interaction occurs with 1a.