Fluid-Solid Interfacial Properties and Drag-Reducing Characterization of the Flexible Conical Microstructured Film Inspired by the Streamlined Body Surface of the Pufferfish.

Given the challenges in accurately replicating the surface of the pufferfish, this study employed three-dimensional (3D) printing to create a model based on inverse modeling. The morphology of the pufferfish exhibits a streamlined configuration, characterized by a gradual widening from the anterior oral region to the central ocular area, followed by a progressive narrowing from the midabdominal region toward the caudal extremity. The RNG k-ε turbulence simulation results demonstrate that the streamlined body surface of the pufferfish diminishes differential pressure resistance. This enhancement promotes laminar flow formation, delays fluid separation, minimizes turbulence-induced vortices, and reduces frictional resistance. Moreover, the pufferfish's supple and uneven outer epidermis was simplified into a flexible, nonsmooth planar film to conduct fluid-solid coupling simulations. These revealed that the pufferfish's unique skin can absorb turbulent energy and minimize momentum transfer between the fluid and the solid film, lowering the fluid resistance during swimming. In summary, The high-efficiency swimming capacity of pufferfish stems not only from their streamlined body surface but also significantly from the unique structural characteristics and mechanical properties of their flexible skin. This research provides critical theoretical underpinnings for the design of functional bionic surfaces aimed at drag reduction.

Understanding the role of sorption and biodegradation in the removal of organic micropollutants by membrane aerated biofilm reactor (MABR) with different biofilm thickness.

The role of sorption and biodegradation in a membrane aerated biofilm reactor (MABR) were investigated for the removal of 10 organic micropollutants (OMPs) including endocrine disruptors and pharmaceutical active compounds. The influence of the biofilm thickness on the mechanisms of removal was analyzed via kinetic test at three different stages. At all biofilm stages, biodegradation was demonstrated to dominate the removal of selected OMPs. Higher OMPs rates of removal via biodegradation (Kbiol) were achieved when biofilm increased its thickness from (stage T1) 0.26 mm, to (stage T2) 0.58 mm and (stage T3) 1.03 mm. At stage T1 of biofilm, heterotrophs contribute predominantly to OMPs degradation. Hydrophilic compounds removal (i.e., acetaminophen) continue to be driven by heterotrophic bacteria at the next stages of biofilm thickness. However, for medium hydrophobic neutral and charged OMPs, the combined action of heterotrophic and enriched nitrifying activity at stages T2 and T3 enhanced the overall removal. A degradation pathway based on heterotrophic activity for acetaminophen and combined action of nitrifiers-heterotrophs for estrone was proposed based on identified metabolites. Although biodegradation dominated the removal of most OMPs, sorption was also observed to be essential in the removal of biologically recalcitrant and lipophilic compounds like triclosan. Furthermore, sorption capacity of apolar compound was enhanced as the biofilm thickness grew and increased in EPS protein fraction. Microbial analysis confirmed the higher abundance of nitrifying and denitrifying activity at stage T3 of biofilm, which not only facilitated near complete ammonium removal but also enhanced degradation of OMPs.

SARS-CoV-2 wastewater-based epidemiology in an enclosed compound: A 2.5-year survey to identify factors contributing to local community dissemination.

Long-term (>2.5 years) surveillance of SARS-CoV-2 RNA concentrations in wastewater was conducted within an enclosed university compound. This study aims to demonstrate how coupling wastewater-based epidemiology (WBE) with meta-data can identify which factors contribute toward the dissemination of SARS-CoV-2 within a local community. Throughout the pandemic, the temporal dynamics of SARS-CoV-2 RNA concentrations were tracked by quantitative polymerase chain reaction and analyzed in the context of the number of positive swab cases, the extent of human movement, and intervention measures. Our findings suggest that during the early phase of the pandemic, when strict lockdown was imposed, the viral titer load in the wastewater remained below detection limits, with <4 positive swab cases reported over a 14-day period in the compound. After the lockdown was lifted and global travel gradually resumed, SARS-CoV-2 RNA was first detected in the wastewater on 12 August 2020 and increased in frequency thereafter, despite high vaccination rates and mandatory face-covering requirements in the community. Accompanied by a combination of the Omicron surge and significant global travel by community members, SARS-CoV-2 RNA was detected in most of the weekly wastewater samples collected in late December 2021 and January 2022. With the cease of mandatory face covering, SARS-CoV-2 was detected in at least two of the four weekly wastewater samples collected from May through August 2022. Retrospective Nanopore sequencing revealed the presence of the Omicron variant in the wastewater with a multitude of amino acid mutations, from which we could infer the likely geographical origins through bioinformatic analysis. This study demonstrated that long-term tracking of the temporal dynamics and sequencing of variants in wastewater would aid in identifying which factors contribute the most to SARS-CoV-2 dissemination within the local community, facilitating an appropriate public health response to control future outbreaks as we now live with endemic SARS-CoV-2.

Malate metabolism mediated by the cytoplasmic malate dehydrogenase gene MdcyMDH affects sucrose synthesis in apple fruit.

The types and proportions of soluble sugar and organic acid in fruit significantly affect flavor quality. However, there are few reports on the crosstalk regulation between metabolism of organic acid and sugar in fruit. Here, we found that the overexpression of cytoplasmic malate dehydrogenase genes (MdcyMDHs) not only increased the malate content but also increased the sucrose concentration in transgenic apple calli and mature fruit. Enzyme activity assays indicated that the overexpression of MdcyMDH1 and MdcyMDH5 enhanced sucrose phosphate synthase (SPS) activity in transgenic materials. RNA-seq and expression analysis showed that the expression levels of SPS genes were up-regulated in MdcyMDH1-overexpressed apple fruit and MdcyMDH5-overexpressed apple calli. Further study showed that the inhibition of MdSPSB2 or MdSPSC2 expression in MdcyMDH1 transgenic fruit could reduce or eliminate, respectively, the positive effect of MdcyMDH1 on sucrose accumulation. Moreover, some starch cleavage-related genes (MdBAM6.1/6.2, MdBMY8.1/8.2, MdISA1) and the key gluconeogenesis-related phosphoenolpyruvate carboxykinase MdPEPCK1 gene were significantly up-regulated in the transcriptome differentially expressed genes of mature fruit overexpressing MdcyMDH1. These results indicate that alteration of malate metabolism mediated by MdcyMDH might regulate the expression of MdSPSs and SPS activity via affecting starch metabolism or gluconeogenesis, and thus accelerate sucrose synthesis and accumulation in fruit.

Investigation of Antibiotic Resistome in Hospital Wastewater during the COVID-19 Pandemic: Is the Initial Phase of the Pandemic Contributing to Antimicrobial Resistance?

Since the COVID-19 pandemic started, there has been much speculation about how COVID-19 and antimicrobial resistance may be interconnected. In this study, untreated wastewater was sampled from Hospital A designated to treat COVID-19 patients during the first wave of the COVID-19 pandemic alongside Hospital B that did not receive any COVID-19 patients. Metagenomics was used to determine the relative abundance and mobile potential of antibiotic resistant genes (ARGs), prior to determining the correlation of ARGs with time/incidence of COVID-19. Our findings showed that ARGs resistant to macrolides, sulfonamides, and tetracyclines were positively correlated with time in Hospital A but not in Hospital B. Likewise, minor extended spectrum beta-lactamases (ESBLs) and carbapenemases of classes B and D were positively correlated with time, suggesting the selection of rare and/or carbapenem-resistant genes in Hospital A. Non-carbapenemase blaVEB also positively correlated with both time and intI1 and was copresent with other ARGs including carbapenem-resistant genes in 6 metagenome-assembled genomes (MAGs). This study highlighted concerns related to the dissemination of antimicrobial resistance (AMR) during the COVID-19 pandemic that may arise from antibiotic use and untreated hospital wastewater.

MdWRKY126 modulates malate accumulation in apple fruit by regulating cytosolic malate dehydrogenase (MdMDH5).

The content of organic acids greatly influences the taste and storage life of fleshy fruit. Our current understanding of the molecular mechanism of organic acid accumulation in apple (Malus domestica) fruit focuses on the aluminum-activated malate transporter 9/Ma1 gene. In this study, we identified a candidate gene, MdWRKY126, for controlling fruit acidity independent of Ma1 using homozygous recessive mutants of Ma1, namely Belle de Boskoop "BSKP" and Aifeng "AF." Analyses of transgenic apple calli and flesh and tomato (Solanum lycopersicum) fruit demonstrated that MdWRKY126 was substantially associated with malate content. MdWRKY126 was directly bound to the promoter of the cytoplasmic NAD-dependent malate dehydrogenase MdMDH5 and promoted its expression, thereby enhancing the malate content of apple fruit. In MdWRKY126 overexpressing calli, the mRNA levels of malate-associated transporters and proton pump genes also significantly increased, which contributed to the transport of malate accumulated in the cytoplasm to the vacuole. These findings demonstrated that MdWRKY126 regulates malate anabolism in the cytoplasm and coordinates the transport between cytoplasm and vacuole to regulate malate accumulation. Our study provides useful information to improve our understanding of the complex mechanism regulating apple fruit acidity.

A study on the effects of mindfulness-based cognitive therapy and loving-kindness mediation on depression, rumination, mindfulness level and quality of life in depressed patients.

OBJECTIVE: To analyze the effects of mindfulness-based cognitive therapy (MBCT) plus loving-kindness mediation (LKM) in depressed patients. METHODS: A total of 125 depressed patients diagnosed in the Department of Psychiatry of our hospital were selected as the research subjects and were randomly divided into a control group (n=62) and an observation group (n=63). The control group was treated with conventional psychological intervention, while the observation group was treated with MBCT plus LKM. The therapeutic outcomes were compared between the two groups. RESULTS: At 2, 4, 6 and 8 weeks after intervention, the Hamilton Depression Rating Scale (HAMD) scores and the scores for introspection and deliberation, forced thinking, rumination of symptoms, treatment, ability and social relationships in the observation group were lower than those in the control group, while Five Facet Mindfulness Questionnaire (FFMQ) scores and the scores for psychology, environment, physiology, social relations, self-acceptance, and self-evaluation in the observation group were higher than those in the control group (P < 0.05). CONCLUSION: MBCT plus LKM can effectively improve depression, rumination, mindfulness level, quality of life, the sense of stigma and degree of self-acceptance in depressed patients.

Glycosides of Caulis Lonicerae inhibits the inflammatory proliferation of IL-1ß-mediated fibroblast-like synovial cells cocultured with lymphocytes.

Caulis Lonicerae, the dried stem of Lonicera japonica, has been confirmed to have antiinflammatory and antioxidant therapeutic effects. In the present study, we aimed to evaluate the functional mechanism of glycosides extracted from Caulis Lonicerae on the inflammatory proliferation of interleukin-1 beta (IL-1ß)-mediated fibroblast-like synoviocytes (FLSs) from rats. Rat FLSs (RSC-364) co-cultured with lymphocytes induced by IL-1ß were used as a cell model. Glycosides in a freeze-dried powder of aqueous extract from Caulis Lonicerae were identified using high-performance liquid chromatography-electrospray ionization/mass spectrometry. After treatment with glycosides, the inflammatory proliferation of FLS, induced by IL-1ß, decreased significantly. Flow cytometry analysis showed that treatment with glycosides restored the abnormal balance of T cells by intervening in the proliferation and differentiation of helper T (Th) cells. Glycosides also inhibited the activation of Janus kinase signal transducer and activator of transcription (JAK-STAT) and nuclear factor (NF)-κB signaling pathways by suppressing the protein expression of key molecules in these pathways. Therefore, we concluded that the glycosides of Caulis Lonicerae can intervene in the differentiation of Th cells, suppressing the activation of JAK-STAT and NF-κB signaling pathways, contributing to the inhibitory effect on inflammatory proliferation of FLS co-cultured with lymphocytes induced by pro-inflammatory cytokines.

Coptidis alkaloids extracted from Coptis chinensis Franch attenuate IFN-γ-induced destruction of bone marrow cells.

Coptidis alkaloids are the primary active components of Coptis chinensis Franch. Clinical and pharmacodynamic studies have confirmed that Coptidis alkaloids have multiple therapeutic effects including anti-inflammatory, antioxidant and antitumor effects, and they are usually used to treat various inflammatory disorders and related diseases. Mouse bone marrow cells (BMCs) were isolated from BALB/c mice. Immune-mediated destruction of BMCs was induced by interferon (IFN) -γ. High-performance liquid chromatography-electrospray ionization/ mass spectrometry was used to analyze the ingredients of the aqueous extract from Coptis chinensis Franch. The results confirmed that Coptidis alkaloids were the predominant ingredients in the aqueous extract from Coptis chinensis. The functional mechanism of Coptidis alkaloids in inhibiting immune-mediated destruction of BMCs was studied in vitro. After Coptidis alkaloid treatment, the percentages of apoptotic BMCs and the proliferation and differentiation of helper T (Th) cells and regulatory T (Treg) cells were measured by flow cytometry. The expression and distribution of T-bet in BMCs were observed by immunofluorescence. Western blotting analysis was used to assay the expression of key molecules in the Fas apoptosis and Jak/Stats signaling pathways in BMCs. We identified five alkaloids in the aqueous extract of Coptis chinensis. The apoptotic ratios of BMCs induced by IFN-γ were decreased significantly after Coptidis alkaloid treatment. The levels of key molecules (Fas, Caspase-3, cleaved Caspase-3, Caspase-8 and Caspase-8) in Fas apoptosis signaling pathways also decreased significantly after treatment with low concentrations of Coptidis alkaloids. Coptidis alkaloids were also found to inhibit the proliferation of Th1 and Th17 cells and induce the differentiation of Th2 and Treg cells; further, the distribution of T-bet in BMCs was decreased significantly. In addition, the levels of Stat-1, phospho-Stat-1 and phospho-Stat-3 were also reduced after Coptidis alkaloid treatment. These results indicate that Coptidis alkaloids extracted by water decoction from Coptis chinensis Franch could inhibit the proliferation and differentiation of T lymphocytes, attenuate the apoptosis of BMCs, and suppress the immune-mediated destruction of the BMCs induced by pro-inflammatory cytokines.

Chinese Herbal Formula, Huayu Tongbi Fang, Attenuates Inflammatory Proliferation of Rat Synoviocytes Induced by IL-1ß by Regulating Proliferation and Differentiation of T Lymphocytes.

The inflammatory proliferation of fibroblast-like synoviocytes (FLSs) and functional imbalances in T lymphocytes play critical roles in the pathogenesis of rheumatoid arthritis (RA). The clinical efficacy of Huayu Tongbi Fang (HYTB, a traditional herbal formula) in RA treatment has been validated. In this study, we aimed to explore the regulatory mechanisms of HYTB on the proliferation and differentiation of T lymphocytes, and the inhibitory effect of HYTB on inflammatory proliferation of FLSs. The RCS-364 (Rat FLSs) cells were cocultured with rat splenic lymphocytes that were induced by interleukin-1ß in Transwell chambers. After freeze-dried HYTB powder treatment, the percentage of T-cell subset and apoptosis rates of FLSs were measured using flow cytometry. Furthermore, protein expression of key molecules of NF-κB and JAK/STAT signaling pathways was quantified using Western blot. The granulocyte-macrophage colony-stimulating factor (GM-CSF) was measured using enzyme-linked immunosorbent assay. The results showed that HYTB could inhibit the inflammatory proliferation of FLSs through inducing cell apoptosis. Additionally, HYTB treatment could intervene in the proliferation and differentiation of T lymphocytes and regulate protein expression of key molecules in NF-κB and JAK/STAT cell signaling pathways. Moreover, it could inhibit FLS activation by suppressing GM-CSF production by T cells and FLSs. Therefore, the HYTB formula should be used as a traditional medicine against RA in modern complementary and alternative therapies.

Metagenomics as a Tool To Monitor Reclaimed-Water Quality.

Many biological contaminants are disseminated through water, and their occurrence has potential detrimental impacts on public and environmental health. Conventional monitoring tools rely on cultivation and are not robust in addressing modern water quality concerns. This review proposes metagenomics as a means to provide a rapid, nontargeted assessment of biological contaminants in water. When further coupled with appropriate methods (e.g., quantitative PCR and flow cytometry) and bioinformatic tools, metagenomics can provide information concerning both the abundance and diversity of biological contaminants in reclaimed waters. Further correlation between the metagenomic-derived data of selected contaminants and the measurable parameters of water quality can also aid in devising strategies to alleviate undesirable water quality. Here, we review metagenomic approaches (i.e., both sequencing platforms and bioinformatic tools) and studies that demonstrated their use for reclaimed-water quality monitoring. We also provide recommendations on areas of improvement that will allow metagenomics to significantly impact how the water industry performs reclaimed-water quality monitoring in the future.

Three-dimensional porous graphene-like biochar derived from Enteromorpha as a persulfate activator for sulfamethoxazole degradation: Role of graphitic N and radicals transformation.

Three-dimensional graphene-like biochar derived from Enteromorpha (EGB) was prepared as a persulfate (PS) activator for sulfamethoxazole (SMX) degradation. The graphitic N in the EGB samples not only endowed the superior binding energy towards SMX adsorption, but also promote the PS binding with the EGB, which was crucial to the catalytic degradation of SMX in EGB/PS system. Different from the radical-based oxidation in biochar prepared at 400 °C via the persistent free radicals (PFRs), both 1O2 and surface electron transfer served as non-radical pathways in the EGB samples prepared above 500 °C, acting together with free radicals (O2∙-) on SMX degradation. Oxidation of SMX and its substructural analogues indicated that the selective oxidizing reaction occurred in the EGB/PS system and the isoxazole ring in SMX molecule was insensitive to be attacked 1O2. In addition, toxicity predication indicated that the overall biotoxicity of the intermediates during SMX degradation was decreased.

Co/Fe and Co/Al layered double oxides ozone catalyst for the deep degradation of aniline: Preparation, characterization and kinetic model.

In this work, Co/Fe and Co/Al layered double oxides (Co/Fe-LDO and Co/Al- LDO)ozone catalysts were obtained from Co/Fe and Co/Al layered double hydroxides intermediates (Co/Fe-LDH and Co/Al-LDH). Firstly, the optimal preparation parameters of the two intermediates were determined, then the morphology and mineralogy microstructure of the derived Co/Fe-LDO and Co/Al- LDO ozone catalysts were systematically studied. Finally, the reaction kinetics of the two ozone catalysts for the deep degradation of aniline wastewater in catalysts/ozone systems were established. The results showed that the optimal preparation conditions were set as pH 12, temperature 60 °C, cobalt­iron ratio 3:1 for Co/Fe-LDH intermediate, and pH 12, temperature 70 °C, cobalt­aluminum ratio 3:1 for Co/Al-LDH intermediate. During calcination treatment, the dehydration and recrystallization effect impelled LDH intermediate to form LDO catalyst. The derived ozone catalysts Co/Fe-LDO and Co/Al-LDO possess layered structure, and Co species was mainly based on Co3O4 as the main mineral phase of the two ozone catalysts. The addition of catalyst can realize the deep ozonation catalysis of aniline wastewater. The kinetic models established on the aniline oxidized by ozone or catalyst/ozone systems were both fitted the first-order reactions, and the reaction activation energy for CODCr and TOC degradation were significantly reduced in catalyst/ozone system.

Effect of interfering IGF-1R by siRNA on cell cycle and apoptosis of hypoxic hepatocellular carcinoma HepG2 cells / 中国肿瘤生物治疗杂志

@# Objective: To explore the effect of interfering insulin-like growth factors-1 receptors (IGF-1R) by small interfering RNA (siRNA) on cell cycle and apoptosis of hypoxic hepatocellular carcinoma HepG2 cells. Methods: The hypoxic hepatocellular carcinoma model was established via cobalt chloride treatment. Three siRNAs targeting IGF1R gene and one negative control siRNA were designed and synthesized. They were transfected into hypoxic HepG2 cells, and 24 h later, the transfection efficiency was detected by fluorescent microscopy. The protein expression of IFG-1R was detected with Western blotting (WB) to screen the siRNA with highest transfection efficacy. The selected siRNA was used to transfect hypoxic HepG2 cells. The proliferation of hypoxic HepG2 cells was determined by MTT assay. Cell cycle distribution and apoptosis were analyzed by Flow cytometry. WB was performed to detect the proteinexpressionsofCDK1,CDK2andCaspase-3inHepG2cells. Results: The hypoxic hepatocellular carcinoma model was successfully established. IGF-1R-siRNA-2 showed the most effective interference efficiency and the most significant knockdown of IGF-1R (all P<0.01). The proliferation of HepG2 cells transfected with IGF-1R siRNA-2 was significantly suppressed (P<0.05 or P<0.01), the cell cycle was blocked at G0/G1 phase (P<0.05), and the apoptosis rate was increased up to (25.3±1.3)% P<0.01). In the meanwhile, the expressions of CDK1 and CDK2 were decreased and the expression of Caspase-3 was increased in hypoxic HepG2 cells after IGF-1R knockdown (P<0.05). Conclusion: Interfering IGF-1R by siRNA inhibits the malignant biological behaviors of hypoxic HepG2 cells via regulating cell cycle and apoptosis-related proteins. IGF-1R may be a potential target for the treatment of HCC.

The combination of Radix Astragali and Radix Angelicae Sinensis attenuates the IFN-γ-induced immune destruction of hematopoiesis in bone marrow cells.

BACKGROUND: Radix Astragali and Radix Angelicae Sinensis are two herbs that compose Danggui Buxue Tang (an herbal formula for treatment of anemia diseases). In this study, we explored the molecular mechanism and effective targets to immune destruction of bone marrow (BM) cells treated with Radix Astragali, Radix Angelicae Sinensis or a combination of two agents. The potential synergic advantages of two herbs should also be explored. METHODS: The constituents of Radix Astragali and Radix Angelicae Sinensis were analyzed by high performance liquid chromatography-electrospray ionization/mass spectrometer system BM cells were separated from limbs of BALB/c mice, and immune destruction was induced with IFN-γ. The percentages of hematopoietic stem cells (HSCs) and CD3+ T cells were detected by flow cytometry. The distribution of T-bet and changes in the combination of SAP and SLAM in BM cells were observed by immunofluorescence. Western blotting was used to assay the expression of key molecules of the eIF2 signaling pathway in BM cells. RESULTS: Seven constituents of Radix Astragali and six constituents of Radix Angelicae Sinensis were identified. The percentages of HSCs increased significantly after treatment with Radix Angelicae Sinensis, especially at high concentrations. The percentages of CD3+ T cells were significantly decreased after Radix Astragali and Radix Angelicae Sinensis treatment. However, the synergistic function of two-herb combinations was superior to that of the individual herbs alone. The distribution of T-bet in BM cells was decreased significantly after Radix Angelicae Sinensis treatment. The number of SLAM/SAP double-stained cells was increased significantly after Radix Astragali treatment at low concentrations. The phosphorylation levels of eIF2α were also reduced after Radix Astragali and Radix Angelicae Sinensis treatment. CONCLUSIONS: Radix Astragali and Radix Angelicae Sinensis could intervene in the immunologic balance of T lymphocytes, inhibit the apoptosis of BM cells induced by immune attack, restore the balance of the T cell immune response network and recover the hematopoietic function of HSCs. The synergistic effects of Radix Astragali and Radix Angelicae Sinensis were superior to those of each herb alone.

Active-Site Conformational Fluctuations Promote the Enzymatic Activity of NDM-1.

ß-Lactam antibiotics are the mainstay for the treatment of bacterial infections. However, elevated resistance to these antibiotics mediated by metallo-ß-lactamases (MBLs) has become a global concern. New Delhi metallo-ß-lactamase-1 (NDM-1), a newly added member of the MBL family that can hydrolyze almost all ß-lactam antibiotics, has rapidly spread all over the world and poses serious clinical threats. Broad-spectrum and mechanism-based inhibitors against all MBLs are highly desired, but the differential mechanisms of MBLs toward different antibiotics pose a great challenge. To facilitate the design of mechanism-based inhibitors, we investigated the active-site conformational changes of NDM-1 through the determination of a series of 15 high-resolution crystal structures in native form and in complex with products and by using biochemical and biophysical studies, site-directed mutagenesis, and molecular dynamics computation. The structural studies reveal the consistency of the active-site conformations in NDM-1/product complexes and the fluctuation in native NDM-1 structures. The enzymatic measurements indicate a correlation between enzymatic activity and the active-site fluctuation, with more fluctuation favoring higher activity. This correlation is further validated by structural and enzymatic studies of the Q123G mutant. Our combinational studies suggest that active-site conformational fluctuation promotes the enzymatic activity of NDM-1, which may guide further mechanism studies and inhibitor design.

Lewis y enhances CAM-DR in ovarian cancer cells by activating the FAK signaling pathway and upregulating Bcl-2/Bcl-XL expression.

Oligosaccharides on the surface of adhesion molecules may contribute to the process of CAM-DR. To investigate the role of the Lewis y antigen in this process, we established a cell adhesion model mediated by the integrin α5ß1-FN interaction in the ovarian cancer cell line, RMG-1-hFUT, which highly expresses Lewis y by transfection with α1,2-fucosyltransferase into RMG-1 cells. Our results indicate that the rates of carboplatin-induced apoptosis and necrosis are reduced in FN-adhered tumor cells, and carboplatin resistance is significantly decreased in the presence of anti-Lewis y antibody. CAM-DR in tumor cells has been correlated with elevated expression of the nuclear anti-apoptotic proteins Bcl-2 and Bcl-XL. Lewis y promotes the expression of the Bcl-2 and Bcl-XL genes by activating the focal adhesion kinase signaling pathway and accelerating their transcription. Thus, Lewis y leads to inhibition of apoptosis and enhancement of CAM-DR by activation of the FAK signaling pathway and upregulation of Bcl-2/Bcl-XL expression in ovarian cancer cell lines.

Expression and correlation of Lewis y antigen and TGF-ß1 in ovarian epithelial carcinoma.

Lewis y is a difucosylated oligosaccharide carried by glycoconjugates on the cell surface. Elevation of Lewis y is frequently observed in epithelial-derived cancers. This study aimed to detect the expression and clinical significance of the Lewis y antigen and TGF-ß1 (transforming growth factor ß1) in ovarian epithelial tumors, and to evaluate the correlation between them. Immunohistochemical staining was used to detect the expression of Lewis y antigen and TGF-ß1 in 60 cases of ovarian epithelial malignant tumors, 20 cases of borderline ovary tumors, 20 cases of benign ovary tumors and 10 cases of normal ovarian tissues. An immunofluorescence double labeling method was also used to detect the correlation between Lewis y antigen and TGF-ß1. The positive rates of Lewis y antigen in ovarian epithelial cancer tissues was 88.33%, significantly higher compared to those of borderline ovarian tumors (60.00%) (P<0.05), benign ovarian tumors (35.00%) (P<0.01) and normal ovarian tissues (0%) (P<0.01). Its expression was not associated with clinical parameters; the positive rates of TGF-ß1 in ovarian epithelial cancers were 78.33%, significantly higher compared to those of benign ovarian tumors (65.00%) (P<0.05) and normal ovarian tissues (40.00%) (P<0.05); the positive rates of the TGF-ß1 and Lewis y were not associated with metastasis of lymph nodes and histological types, differentiation degree and clinical stage (P>0.05). Expression of Lewis y antigen and TGF-ß1 was significantly positively associated with epithelial carcinoma. Close correlation between Lewis y, TGF-ß1 and ovarian cancer was observed. Altered expression of Lewis y antigen may cause changes in TGF-ß1 expression. Lewis y can increase the growth of ovarian cancer cells and the invasion ability by promoting TGF-ß1 abnormal expression and by promoting angiogenesis and a change in its signal transduction pathway. This study provides theoretical evidence for the development of ovarian cancer biological treatments.

The stimulation of IGF-1R expression by Lewis(y) antigen provides a powerful development mechanism of epithelial ovarian carcinoma.

OBJECTIVE: This study aimed to measure and correlate the expression of insulin-like growth factor receptor-1 (IGF-1R) and the Lewis(y) antigen in ovarian cancer cell lines and tissue samples. METHODS: Reverse transcriptase PCR (RT-PCR), Western blotting, immunoprecipitation, immunohistochemistry, and immunofluorescence double-labeling techniques were applied to detect and measure the expression of Lewis(y) and IGF-1R. RESULTS: In α1,2-fucosyltransferase (α1,2-FT)-transfected cells, IGF-1R expression was significantly upregulated compared with cells that do not overexpress α1,2-FT (P < 0.05). The amount of Lewis(y) expressed on IGF-1R increased 1.81-fold in α1,2-FT-overexpressing cells (P < 0.05), but the ratio of Lewis(y) expressed on IGF-1R to total IGF-1R was unaltered between two cells (P > 0.05). In malignant epithelial ovarian tumors, the positivity rates of Lewis(y) and IGF-1R detection were 88.3% and 93.33%, respectively, which is higher than the positivity rates in marginal (60.00% and 63.33%, all P < 0.05), benign (33.00% and 53.33%, all P < 0.01), and normal (0% and 40%, all P < 0.01) ovarian samples. No correlations were detected in positivity rates of Lewis(y) or IGF-1R expression with respect to clinicopathological parameters in ovarian cancers (all P > 0.05). Both IGF-1R and Lewis(y) were highly expressed in ovarian cancer tissues, and their expression levels were positively correlated (P < 0.05). CONCLUSION: Overexpression of Lewis(y) results in overexpression of IGF-1R. Both IGF-1R and Lewis(y) are associated with the occurrence and development of ovarian cancers.

Study on the expression and clinical significances of lewis y antigen and integrin αv, ß3 in epithelial ovarian tumors.

OBJECTIVE: To detect the expression and clinical significances of Lewis y antigen and integrin αv, ß3 in epithelial ovarian tumors, and to explore the expression correlation between Lewis y antigen and integrin αv, ß3. METHODS: Immunohistochemical staining was performed in 95 cases of epithelial ovarian cancer, 37 cases of borderline tumors, 20 cases of benign tumors, and 20 cases of normal ovarian tissue, for the detection of Lewis y antigen and integrin αv, ß3 expressions, and to analyze the relationship between Lewis y antigen and integrin, and the relationship between clinical and pathological parameters of ovarian cancer. In addition, immunofluorescence double labeling was utilized to detect the expression correlation between Lewis y antigen and integrin αv, ß3 in ovarian cancer. RESULTS: In epithelial ovarian tumors, the expression rate of Lewis y antigen was 81.05%, significantly higher than that of borderline (51.53%) (P < 0.05) and benign (25%) (P < 0.01) tumors, and normal ovarian tissues (0) (P < 0.01). The expression rate of integrin αv, ß3 in malignant epithelial ovarian tumors was 78.95% and 82.11%, respectively, significantly higher than that of the borderline (45.94%, 40.54%) (both P < 0.05), benign group (10.00%, 15.00%) (both P < 0.01) and normal ovary group (5%, 15%) (both P < 0.01). CONCLUSIONS: Lewis y and integrins αv, ß3 are relevant to pelvic and abdominal diffusion and metastasis of ovarian cancer cells, suggesting that these two molecules mediate a boosting function for tumor metastasis.