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1.
ACS Nano ; 2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39066710

ABSTRACT

Radiotherapy (RT)-induced in situ vaccination greatly promotes the development of personalized cancer vaccines owing to the massive release of antigens initiated by tumor-localized RT eliciting the tumor-specific immune response. However, its broad application in cancer treatment is seriously impeded by poor antigen cross-presentation, low response rate, and short duration of efficacy. Herein, the tumor-antigen-capturing nanosystem dAuNPs@CpG consisting of gold nanoparticles, 3,5-cyclohexanedione (CHD), and immunoadjuvant CpG were fabricated to enhance RT-induced vaccination. Taking advantage of the specific covalent binding between CHD and sulfenic acids of antigen proteins, we show that this nanoplatform has an unexpected potential to capture the sulfenylated tumor-derived protein antigens (TDPAs) induced by RT to in situ generate a vaccination effect, achieving significant growth suppression of both primary and distant tumors in combination with PD-1 blockade. We thus believe that our work presents a powerful and effective means to improve the synergistic tumor radioimmunotherapy.

2.
Mar Life Sci Technol ; 6(1): 168-181, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38433963

ABSTRACT

Hadal trenches are characterized by enhanced and infrequent high-rate episodic sedimentation events that likely introduce not only labile organic carbon and key nutrients but also new microbes that significantly alter the subseafloor microbiosphere. Currently, the role of high-rate episodic sedimentation in controlling the composition of the hadal subseafloor microbiosphere is unknown. Here, analyses of carbon isotope composition in a ~ 750 cm long sediment core from the Challenger Deep revealed noncontinuous deposition, with anomalous 14C ages likely caused by seismically driven mass transport and the funneling effect of trench geomorphology. Microbial community composition and diverse enzyme activities in the upper ~ 27 cm differed from those at lower depths, probably due to sudden sediment deposition and differences in redox condition and organic matter availability. At lower depths, microbial population numbers, and composition remained relatively constant, except at some discrete depths with altered enzyme activity and microbial phyla abundance, possibly due to additional sudden sedimentation events of different magnitude. Evidence is provided of a unique role for high-rate episodic sedimentation events in controlling the subsurface microbiosphere in Earth's deepest ocean floor and highlight the need to perform thorough analysis over a large depth range to characterize hadal benthic populations. Such depositional processes are likely crucial in shaping deep-water geochemical environments and thereby the deep subseafloor biosphere. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00212-y.

3.
ACS Nano ; 17(24): 25147-25156, 2023 Dec 26.
Article in English | MEDLINE | ID: mdl-38063344

ABSTRACT

X-ray-induced radiodynamic therapy (RDT) that can significantly reduce radiation dose with an improved anticancer effect has emerged as an attractive and promising therapeutic modality for tumors. However, it is highly significant to develop safe and efficient radiosensitizing agents for tumor radiation therapy. Herein, we present a smart nanotheranostic system FA-Au-CH that consists of gold nanoradiosensitizers, photosensitizer chlorin e6 (Ce6), and folic acid (FA) as a folate-receptor-targeting ligand for improved tumor specificity. FA-Au-CH nanoparticles have been demonstrated to be able to simultaneously serve as radiosensitizers and RDT agents for enhanced computed tomography (CT) imaging-guided radiotherapy (RT) of colon carcinoma, owing to the strong X-ray attenuation capability of high-Z elements Au and Hf, as well as the characteristics of Hf that can transfer radiation energy to Ce6 to generate ROS from Ce6 under X-ray irradiation. The integration of RT and RDT in this study demonstrates great efficacy and offers a promising therapeutic modality for the treatment of malignant tumors.


Subject(s)
Carcinoma , Colonic Neoplasms , Photochemotherapy , Porphyrins , Radiation-Sensitizing Agents , Humans , Porphyrins/therapeutic use , Hafnium , Gold , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/radiotherapy , Radiation-Sensitizing Agents/pharmacology , Radiation-Sensitizing Agents/therapeutic use , Cell Line, Tumor
4.
Angew Chem Int Ed Engl ; 62(19): e202218969, 2023 05 02.
Article in English | MEDLINE | ID: mdl-36912594

ABSTRACT

Mitochondrial RNA (mtRNA) plays a critical role in synthesis of mitochondrial proteins. Interfering mtRNA is a highly effective way to induce cell apoptosis. Herein, we report a near-infrared (NIR) light-mediated mitochondrial RNA modification approach for long-term imaging and effective suppression of tumors. A tumor-targetable NIR fluorescent probe f-CRI consisting of a cyclic RGD peptide, a NIR fluorophore IR780, and a singlet oxygen (1 O2 )-labile furan group for RNA modification was rationally designed and synthesized. This probe was demonstrated to dominantly accumulate in cellular mitochondria and could be covalently conjugated onto mtRNA upon 808 nm irradiation resulting in prolonged retention in tumors. More notably, this covalent modification of mtRNA by f-CRI could perturb the function of mitochondria leading to remarkable tumor suppression. We thus envision that our current approach would offer a potential approach for cancer RNA interference therapeutics.


Subject(s)
Neoplasms , Photochemotherapy , Humans , RNA, Mitochondrial/metabolism , RNA, Mitochondrial/therapeutic use , RNA Interference , Neoplasms/drug therapy , Photochemotherapy/methods , Mitochondria/metabolism , Fluorescent Dyes/metabolism
5.
J Am Chem Soc ; 144(50): 23061-23072, 2022 12 21.
Article in English | MEDLINE | ID: mdl-36503221

ABSTRACT

RNA interference (RNAi) has proved to be a promising modality for disease treatment. However, the promise of conventional RNA therapeutics for clinical application is severely impeded by low delivery efficiency and susceptibility of RNAs to serum RNases. Therefore, developing advanced RNAi technology is an increasing demand for achieving precise medicine. Herein, for the first time, we propose an alkaline phosphatase (ALP)-controllable and red light-activated RNA modification (ALARM) approach for anti-tumor therapeutic application. An ALP-responsive NIR fluorogenic probe f-RCP consisting of a tumor-targeting cyclic RGD peptide, an ALP-activated photosensitizer CyOP, and an 1O2-susceptible furan module for RNA modification was rationally designed and synthesized. Studies have demonstrated that f-RCP can specifically target to liver carcinoma HepG2 cells and spontaneously emit activated NIR/photoacoustic signals upon cleavage by the ALP enzyme, allowing for sensitive detection of ALP-positive tumors. More notably, we surprisingly found that the capability of f-RCP producing singlet oxygen (1O2) under red light irradiation could be simultaneously unlocked, which can ignite the covalent cyclization reaction between furan and nucleobases of intracellular RNA molecules, leading to significant mitochondrial damage and severe apoptosis of tumor cells, in consequence realizing efficient tumor suppression. Most importantly, the potential therapeutic mechanism was first explored on the transcriptomic level. This delicate ALARM strategy may open up new insights into cancer gene therapy.


Subject(s)
Alkaline Phosphatase , Neoplasms , Humans , Light , Fluorescent Dyes/chemistry , RNA
6.
Int J Biol Macromol ; 205: 193-202, 2022 Apr 30.
Article in English | MEDLINE | ID: mdl-35181324

ABSTRACT

Curdlan is a neutral, water-insoluble, unbranched, linear ß-(1,3)-glucan. This study explored the roles of exoR and exoX in curdlan biosynthesis in Agrobacterium sp. ATCC 31749. The microcapsule biosynthesis of ΔexoR strain was reduced, and the motility of this strain increased remarkably compared with the wild-type (WT) strain during the cell growth phase. The curdlan yields of ΔexoR and ΔexoX strains enhanced by 19% and 17%, and the glucose utilization increased by 12% and 11%, respectively, compared with the WT strain during batch fermentation. By contrast, the curdlan yields of exoR and exoX overexpression strains decreased by 28% and 33%, respectively. The gel strength produced by ΔexoR and exoX overexpression strains decreased compared with the WT strain. RT-qPCR analysis at the transcriptional level revealed that key genes in exopolysaccharide synthesis and central metabolic pathways were up-regulated in ΔexoX and ΔexoR strains during gel production. Metabolomics analysis of ΔexoR and ΔexoX mutants proved the rates of central metabolic and electron transport chain were accelerated.


Subject(s)
Agrobacterium , beta-Glucans , Agrobacterium/genetics , Agrobacterium/metabolism , Fermentation , beta-Glucans/metabolism
7.
PeerJ ; 7: e7458, 2019.
Article in English | MEDLINE | ID: mdl-31523497

ABSTRACT

PURPOSE: Radioactive iodine (RAI) is widely used for adjuvant therapy after thyroidectomy, while its value for thyroid cancer has been controversial recently. The primary objectives of this study were to clarify the influence of Radioactive iodine (RAI) on the survival in rare oxyphilic subtype of thyroid cancer (Hürthle cell carcinoma, HCC). METHODS: Patients diagnosed with oxyphilic thyroid carcinoma from 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Results Program database. The Kaplan-Meier method was used to compare overall survival (OS) and cancer-specific survival (CSS) among patients who had adjuvant RAI use or not. Univariate and multivariate Cox proportional hazard models were performed for survival analysis, and subsequently visualized by nomogram. RESULTS: In all, 2,799 patients were identified, of which 1529 patients had adjuvant RAI use while 1,270 patients had not. Based on multivariate Cox analysis, the RAI therapy confers an improved OS for HCC patients (HR = 0.57, 95% CI [0.44-0.72], P < 0.001), whereas it has no significant benefit in the survival analysis regarding CSS (HR = 0.79, 95% CI [[0.47-1.34], P = 0.382). In a subgroup analysis, the same survival benefit of RAI treatment on OS, but not CSS was observed among patients stratified by AJCC stage and tumor extension. Nevertheless, patients with regional lymph node metastasis benefited from RAI therapy both in OS and CSS (P < 0.001, respectively). Furthermore, nomograms used for predicting long term survival of HCC patients exhibited a better prediction power for OS compared with traditional tumor, nodal and metastatic (TNM) stage made by American Joint Committee on Cancer (AJCC) (C-index = 0.833 of the nomogram model vs. 0.696 of the AJCC system). CONCLUSIONS: This study suggests that RAI therapy is significantly associated with improved OS in patients with Hürthle cell carcinoma. However, there was no association between treatment with radioiodine and CSS, possibly due to small number of deaths that were related to HCC.

8.
Indian J Orthop ; 53(4): 518-524, 2019.
Article in English | MEDLINE | ID: mdl-31303667

ABSTRACT

PURPOSE: To evaluate the therapeutic effects of combined atlas fracture with type II (C1-type II) odontoid fractures and to outline a management strategy for it. PATIENTS AND METHODS: Twenty three patients with C1-type II odontoid fractures were treated according to our management strategy. Nonoperative external immobilization in the form of cervical collar and halo vest was used in 13 patients with stable atlantoaxial joint. Surgical treatment was early performed in 10 patients whose fractures with traumatic transverse atlantal ligament disruption or atlantoaxial instability. The visual analog scale (VAS), neck disability index (NDI) scale, and American Spinal Injury Association (ASIA) scale at each stage of followup were then collected and compared. RESULTS: Compared to pretreatment, the VAS score, NDI score, and ASIA scale were improved among both groups at followup evaluation after treatment. However, in the nonsurgical group, one patient (1/11) developed nonunion which required surgical treatment in later stage and one patient (1/13) with halo vest immobilization had happened pin site infection. Two patients of the surgical group (2/11) had appeared minor complications: occipital cervical pain in one case and cerebrospinal fluid leakage in one case. Two patients (2/23) were excluded from nonsurgical treatment group because their followup period was less than 12 months. Twenty one patients were followed up regularly with an average of 23.9 months (range 15-45 months). CONCLUSIONS: We outlined our concluding management principle for the treatment of C1-type II odontoid fractures based on the nature of C1 fracture and atlantoaxial stability. The treatment principle can obtain satisfactory results for the management of C1-type II odontoid fractures.

9.
Mol Med Rep ; 18(6): 5594-5602, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30365099

ABSTRACT

Osteoarthritis (OA) is a chronic arthropathy that occurs in the middle­aged and elderly population. The present study aimed to identify gene signature differences between synovial cells from OA synovial membrane with and without inflammation, and to explain the potential mechanisms involved. The differentially expressed genes (DEGs) between 12 synovial membrane with inflammation and 12 synovial membrane without inflammation from the dataset GSE46750 were identified using the Gene Expression Omnibus 2R. The DEGs were subjected to enrichment analysis, protein­protein interaction (PPI) analysis and module analysis. The analysis results were compared with text­mining results. A total of 174 DEGs were identified. Gene Ontology enrichment results demonstrated that functional molecules encoded by the DEGs primarily had extracellular location, molecular functions predominantly involving 'chemokine activity' and 'cytokine activity', and were associated with biological processes, including 'inflammatory response' and 'immune response'. The Kyoto Encyclopedia of Genes and Genomes results demonstrated that DEGS may function through pathways associated with 'rheumatoid arthritis', 'chemokine signaling pathway', 'complement and coagulation cascades', 'TNF signaling pathway', 'intestinal immune networks for IgA production', 'cytokine­cytokine receptor interaction', 'allograft rejection', 'Toll­like receptor signaling pathway' and 'antigen processing and presentation'. The top 10 hub genes [interleukin (IL)6, IL8, matrix metallopeptidase (MMP)9, colony stimulating factor 1 receptor, FOS proto­oncogene, AP1 transcription factor subunit, insulin­like growth factor 1, TYRO protein tyrosine kinase binding protein, MMP3, cluster of differentiation (CD)14 and CD163] and four gene modules were identified from the PPI network using Cytoscape. In addition, text­mining was used to identify the commonly used drugs and their targets for the treatment of OA. It was initially verified whether the results of the present study were useful for the study of OA treatment targets and pathways. The present study provided insight for the molecular mechanisms of OA synovitis. The hub genes and associated pathways derived from analysis may be targets for OA treatment. IL8 and MMP9, which were validated by text­mining, may be used as molecular targets for the OA treatment, while other hub genes require further validation.


Subject(s)
Computational Biology , Osteoarthritis/genetics , Osteoarthritis/metabolism , Signal Transduction , Synovial Membrane/metabolism , Transcriptome , Computational Biology/methods , Databases, Genetic , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic , Gene Ontology , Gene Regulatory Networks , Humans , Osteoarthritis/pathology , Protein Interaction Mapping , Protein Interaction Maps , Synovial Membrane/pathology
10.
Oncol Lett ; 15(5): 7776-7782, 2018 May.
Article in English | MEDLINE | ID: mdl-29731903

ABSTRACT

Matrix metalloproteinase (MMP)-21 and MMP-28, or epilysin, are overexpressed during the invasion and metastasis of solid tumors. The present study investigated MMP-21 and MMP-28 expression levels in human gastric cancer using tissue microarray (TMA) analysis, and determined their association with clinicopathological characteristics and patient prognosis. TMA blocks, including 436 cases of gastric cancer and 92 non-cancerous adjacent gastric tissues, were investigated using immunohistochemistry. Staining results were analyzed statistically in association with various clinicopathological characteristics and overall survival. The MMP-21 and MMP-28 positive detection rate was 31.9% (139/436) and 34.4% (150/436), respectively, in the gastric carcinoma tissue specimens. MMP-21 and MMP-28 expression levels were negative in the 92 normal gastric tissue samples. In patients with gastric cancer, positive expression of MMP-21 and MMP-28 was correlated with tumor diameter, depth of invasion, vessel invasion, lymph node and distant metastases and tumor-node-metastasis stage. The overall survival rate was significantly lower in MMP-21 and MMP-28-positive compared with negative patients. Cox multivariate analysis revealed that MMP-21 and MMP-28 levels were independent predictors of survival in patients with gastric cancer. These findings emphasize the importance of MMP-21 and MMP-28, which may serve as novel and independent prognostic markers for the invasion and metastasis of human gastric cancer.

11.
Hum Pathol ; 78: 44-53, 2018 08.
Article in English | MEDLINE | ID: mdl-29698700

ABSTRACT

To investigate the expression and clinical significance of long noncoding RNA (lncRNA) in gastric cancer, we applied microarray analysis to obtain expression profiles of protein-coding genes and lncRNAs in tumor and paired adjacent nontumor tissues. We found that 41 lncRNAs were up-regulated and 31 lncRNAs were down-regulated more than 2-fold in gastric cancer versus noncancerous tissues (ratio >2.0, P < .01). We established a coexpression network of the differentially expressed lncRNAs and targeted coding genes that included 17 lncRNAs and 16 coding genes. Because the results of microarray analysis showed that lncRNA M26317 was up-regulated in gastric cancer tissues, we examined the expression level of M26317 in 103 gastric cancer tissues by reverse-transcription polymerase chain reaction and 436 gastric cancer tissues by in situ hybridization. Our data confirmed that M26317 was up-regulated in gastric cancer tissues. Moreover, expression of M26317 correlated with patient age, size of tumor, Lauren's classification, depth of invasion, lymph node and distant metastasis, TNM stage, and poor prognosis (P < .05), but was not associated with sex, location of tumor, and differentiation (P > .05). M26317 may have an important role in malignant transformation and metastasis of gastric cancer.


Subject(s)
Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic/genetics , RNA, Long Noncoding/genetics , Stomach Neoplasms/genetics , Female , Humans , Male , Middle Aged , Prognosis , Stomach Neoplasms/diagnosis , Stomach Neoplasms/therapy , Transcriptional Activation/genetics , Up-Regulation
12.
Pathol Res Pract ; 214(4): 536-541, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29573865

ABSTRACT

BACKGROUND: The present study examined the clinical significance of metastasis-associated protein 1 (MTA1) in the progression and patient survival of gastric cancer. METHODS: Paraffin-embedded resected tissues of gastric cancer mucosa (n = 436) and adjacent normal mucosa (n = 92) were assessed immunohistochemically for MTA1 protein, and scored according to the percentage of cells positively stained for MTA1 combined with stain intensity. Associations between MTA1 staining scores and clinicopathological factors, including survival time, were evaluated. RESULTS: The staining scores for MTA1 were significantly higher in gastric cancer tissues than in matched normal tissues. MTA1 scores positively correlated with tumor size, depth of invasion, presence of lymph node metastasis, lymphatic involvement, venous invasion, distal metastasis, and advanced clinical staging. Patients with high MTA1 scores in gastric cancer tissues had a significantly lower five-year survival rate compared with patients with low MTA1 scores. The multivariate analysis indicated that MTA1 protein levels in resected gastric cancer tissues, as reflected by immunohistochemical staining, are an independent prognostic index of gastric carcinoma (P < 0.01). CONCLUSION: MTA1 immunopositivity was significantly associated with progression of gastric cancer, and may be helpful in gastric cancer prognosis.


Subject(s)
Histone Deacetylases/metabolism , Repressor Proteins/metabolism , Stomach Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Disease Progression , Female , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , Humans , Lymphatic Metastasis , Male , Middle Aged , Prognosis , Stomach Neoplasms/diagnosis , Stomach Neoplasms/metabolism , Survival Rate , Trans-Activators
13.
Oncotarget ; 8(48): 83673-83683, 2017 Oct 13.
Article in English | MEDLINE | ID: mdl-29137373

ABSTRACT

This study aims to investigate the prognostic power of carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) in gastric cancer (GC) and its potential role in cancer development and progression. Data mining results show that CEACAM6 is overexpressed in gastric cancer and is correlated with lymph node metastasis. Subsequently, immunohistochemical staining was performed to determine CEACAM6 protein levels in paraffin gastric tumor specimens. Real-time reverse-transcription-polymerase chain reaction (RT-PCR) was conducted to detect CEACAM6 mRNA levels in fresh GC samples. CEACAM6 protein and mRNA levels were significantly up regulated in GC compared with paired normal mucosa. The IHC staining intensity of CEACAM6 was positively correlated with tumor size, Lauren's classification, vascular invasion, lymph node metastasis, distant metastasis, and TNM stage. CEACAM6 expression was inversely correlated with the five-year survival rate of GC patients. Cox multivariate analysis results demonstrated that the overall survival was independently correlated with CEACAM6 expression. A significant association was observed between CEACAM6 and distant metastases. Network analysis of downstream gene signatures revealed several hub genes such as SRC and DNM1L etc. which may mediating tumor promoting functions of CEACAM6. Further data mining discovered that Tamoxifen etc. could be therapeutic alternatives for gastric patients with CEACAM6 overexpression. Collectively, CEACAM6 overexpression is a common characteristic of GC and is associated with poor 5 year survival rate in GC. Besides, potential molecular mechanisms and treatment options were also provided.

14.
Oncol Lett ; 13(5): 3556-3566, 2017 May.
Article in English | MEDLINE | ID: mdl-28521458

ABSTRACT

Musashi-1, an evolutionally conserved RNA-binding protein, has been implicated in the promotion of pathological stem cell proliferation, including tumorigenesis. The objective of the present study was to evaluate the expression of Musashi-1 protein and its implications in the progression and prognosis of gastric cancer. The expression level of Musashi-1 protein in gastric cancer was determined by western blotting and immunohistochemistry, and compared with the clinicopathological parameters. The present study revealed that the expression level of Musashi-1 protein in gastric cancer was significantly upregulated and correlated with the tumor size, tumor-node-metastasis (TNM) stage, Lauren classification, depth of invasion, vessel invasion, lymph node metastasis and distant metastasis. The mean survival time for patients with low expression levels of Musashi-1 was significantly longer compared with patients with high expression levels of Musashi-1. For each TNM stage, the mean survival time for patients with a low Musashi-1 expression levels was also significantly longer compared with patients with a high Musashi-1 expression level. Notably, TNM stage II patients with a low Musashi-1 expression level demonstrated a longer mean survival time compared with TNM stage I patients with high Musashi-1 expression level (56.8 vs. 42.3 months; P=0.001), and TNM stage III patients with low Musashi-1 expression level exhibited a longer mean survival time compared with TNM stage II patients with a high Musashi-1 expression level (44.0 vs. 33.8 months; P=0.034). Multivariate Cox's regression test demonstrated that Musashi-1 protein expression level was an independent prognostic indicator for the survival rate of the patients with gastric cancer. The results of the present study highlighted an important role for Musashi-1 protein in the progression of gastric cancer. The detection of the Musashi-1 protein expression level alone or in combination with TNM staging may aid the prediction of the prognosis of patients with gastric cancer.

15.
West J Nurs Res ; 39(7): 924-941, 2017 07.
Article in English | MEDLINE | ID: mdl-27621272

ABSTRACT

This purpose of this article is to describe how we adhere to the Patient-Centered Outcomes Research Institute's (PCORI) methodology standards relevant to the design and implementation of our PCORI-funded study, the PAIN RelieveIt Trial. We present details of the PAIN RelieveIt Trial organized by the PCORI methodology standards and components that are relevant to our study. The PAIN RelieveIt Trial adheres to four PCORI standards and 21 subsumed components. The four standards include standards for formulating research questions, standards associated with patient centeredness, standards for data integrity and rigorous analyses, and standards for preventing and handling missing data. In the past 24 months, we screened 2,837 cancer patients and their caregivers; 874 dyads were eligible; 223.5 dyads consented and provided baseline data. Only 55 patients were lost to follow-up-a 25% attrition rate. The design and implementation of the PAIN RelieveIt Trial adhered to PCORI's methodology standards for research rigor.


Subject(s)
Hospice Care/methods , Nursing Methodology Research , Pain/drug therapy , Patient Outcome Assessment , Research Design , Aged , Caregivers/psychology , Ethnicity , Female , Humans , Male , Middle Aged , Neoplasms/therapy , Pain/psychology , Pain Measurement
16.
Biotechnol Lett ; 39(1): 55-63, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27627899

ABSTRACT

OBJECTIVE: To develop a strategy for producing N-acetyl-D-neuraminic acid (Neu5Ac), which is often synthesized from exogenous N-acetylglucosamine (GlcNAc) and pyruvate, but without using pyruvate. RESULT: An efficient three-module whole-cell biocatalyst strategy for Neu5Ac production by utilizing intracellular phosphoenolpyruvate was established. In module I, the synthetic pathway was constructed by coexpressing GlcNAc 2-epimerase from Anabaena sp. CH1 and Neu5Ac synthase from Campylobacter jejuni in Escherichia coli. In module II, the Neu5Ac degradation pathway of E. coli was knocked out, resulting in 2.6 ± 0.06 g Neu5Ac l-1 after 72 h in Erlenmeyer flasks. In module III, the transmembrane mode of GlcNAc was modified by disruption of GlcNAc-specific phosphotransferase system and Neu5Ac now reached 3.7 ± 0.04 g l-1. In scale-up catalysis with a 1 l fermenter, the final Neu5Ac yield was 7.2 ± 0.08 g l-1. CONCLUSION: A three-module whole-cell biocatalyst strategy by manipulating synthetic, degradation and transmembrane pathways in E. coli was an economical method for Neu5Ac production.


Subject(s)
N-Acetylneuraminic Acid/metabolism , Acetylglucosamine/metabolism , Anabaena/metabolism , Biocatalysis , Campylobacter jejuni/metabolism , Carbohydrate Epimerases/metabolism , Carrier Proteins/metabolism , Escherichia coli/metabolism , Phosphoenolpyruvate/metabolism , Pyruvic Acid/metabolism
17.
Oncol Lett ; 14(6): 7288-7296, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29344165

ABSTRACT

Forkhead box M1 (FOXM1) and urokinase-type plasminogen activator (uPA) are overexpressed and associated with the pathogenesis of multiple types of human malignancy. The aims of the present study were to investigate FOXM1 and uPA expression levels in human gastric cancer using tissue microarray techniques; determining their association with clinicopathological characteristics as well as their prognostic value. Tissue microarray blocks, comprising 436 gastric cancer cases and 92 non-cancerous adjacent normal gastric tissues, were analyzed for FOXM1 and uPA protein expression levels using immunohistochemistry. The results were analyzed statistically in association with various clinicopathological characteristics and overall survival rates. FOXM1 and uPA were detected in 78.67 (343/436) and 83.26% (363/436) of cancer samples, respectively. FOXM1 and uPA were not expressed in the 92 normal gastric tissue samples. In gastric cancer, FOXM1 and uPA levels were associated with tumor size, depth of invasion, tumor-node-metastasis (TNM) stage, lymph node metastasis, vessel invasion and distant metastases. The overall survival rate was significantly decreased in patients expressing FOXM1 and uPA compared with FOXM1- and uPA-negative patients. Coxs multivariate analysis revealed that age, depth of invasion and expression levels of FOXM1 and uPA are independent predictors of survival in patients with gastric cancer. These results indicated that increased FOXM1 and uPA expression levels are associated with the invasive and metastatic processes in human gastric cancer, and inversely associated with patient prognosis. Therefore, FOXM1 and uPA may serve as novel prognostic markers independent of, but supplementing, the TNM staging system.

18.
BMJ Open ; 6(12): e013466, 2016 12 21.
Article in English | MEDLINE | ID: mdl-28003296

ABSTRACT

OBJECTIVE: The Truth about Suicide video has been widely used but has never been empirically tested regarding its cultural appropriateness for Asian Americans. The purpose of the study was to determine the feasibility of using the video in a web-based suicide awareness programme for Asian American and non-Hispanic white college students. METHODS: A cross-sectional, comparative, web-based study was conducted with 227 Asian Americans and 204 non-Hispanic whites at a university in the Midwest region of the USA. Study participants completed a questionnaire measuring their cultural orientation and attitudes towards suicide, watched the 27 min video, completed a debriefing session and evaluated the video's overall suitability. RESULTS: Asian Americans rated the suicide awareness video significantly lower for cultural relevance than did non-Hispanic whites (F=5.479, p=0.02). Collectivist cultural orientation was a significant predictor for cultural relevance, credibility and appeal; however, evaluation of the video's cultural relevance was negatively affected by Asian ethnicity. CONCLUSIONS: Cultural orientation and race/ethnicity should be strongly considered when web-based suicide awareness programmes are developed for college students.


Subject(s)
Asian , Attitude , Culture , Health Education/methods , Suicide , Universities , White People , Adolescent , Adult , Awareness , Cross-Cultural Comparison , Cross-Sectional Studies , Cultural Competency , Female , Humans , Internet , Male , Midwestern United States , Students , Surveys and Questionnaires , Young Adult
19.
Front Public Health ; 4: 272, 2016.
Article in English | MEDLINE | ID: mdl-28018897

ABSTRACT

BACKGROUND/AIMS: This study's objective was to evaluate a patient-centered educational electronic tablet application, "My Interventional Drug-Eluting Stent Educational App" (MyIDEA) to see if there was an increase in patient knowledge about dual antiplatelet therapy (DAPT) and medication possession ratio (MPR) compared to treatment as usual. METHODS: In a pilot project, 24 elderly (≥50 years old) research participants were recruited after a drug-eluting stent. Eleven were randomized to the control arm and 13 to the interventional arm. All the participants completed psychological and knowledge questionnaires. Adherence was assessed through MPR, which was calculated at 3 months for all participants who were scheduled for second and third follow-up visits. RESULTS: Relative to control, the interventional group had a 10% average increase in MPR. As compared to the interventional group, more patients in the control group had poor adherence (<80% MPR). The psychological data revealed a single imbalance in anxiety between the control and interventional groups. On average, interventional participants spent 21 min using MyIDEA. DISCUSSION: Consumer health informatics has enabled us to engage patients with their health data using novel methods. Consumer health technology needs to focus more on patient knowledge and engagement to improve long-term health. MyIDEA takes a unique approach in targeting DAPT from the onset. CONCLUSION: MyIDEA leverages patient-centered information with clinical care and the electronic health record highlighting the patients' role as a team member in their own health care. The patients think critically about adverse events and how to solve issues before leaving the hospital.

20.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 45(1): 24-30, 2016 01.
Article in Chinese | MEDLINE | ID: mdl-27045237

ABSTRACT

OBJECTIVE: To investigate the association of neuroendocrine differentiation with progression and prognosis of gastric adenocarcinoma. METHODS: Clinicopathological data of 240 patients with gastric adenocarcinomas were retrospectively analyzed. The expression of chromogranin A, synaptophysin and secrectagogin in cancer tissue was assessed by immunohistochemistry. The association of neuoroendocrine differentiation parameters with disease progression and survival of patients was analyzed. RESULTS: The expression of synaptophysin was positively correlated with depth of invasion and secretagogin more often expressed in cases with lymph node metastasis. In Lauren diffuse type of cancer, expression of chromogranin A and secretagogin was unfavorable prognostic predictor. In TNM stage II adenocarcinoma, expression of chromogranin A and synaptophysin related to poor survival, and multivariate Cox proportional hazard model showed that synaptophysin was an independent predictor for poor survival. CONCLUSION: Neuroendocrine differentiation predicts deeper depth of invasion, more possibility of lymph node metastasis and poor survival in gastric adenocarcinoma.


Subject(s)
Adenocarcinoma/pathology , Neuroendocrine Tumors/pathology , Stomach Neoplasms/pathology , Adenocarcinoma/diagnosis , Biomarkers, Tumor/metabolism , Chromogranin A/metabolism , Disease Progression , Humans , Immunohistochemistry , Lymphatic Metastasis , Neoplasm Staging , Neuroendocrine Tumors/diagnosis , Prognosis , Proportional Hazards Models , Retrospective Studies , Secretagogins/metabolism , Stomach Neoplasms/diagnosis , Synaptophysin/metabolism
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