Artykuły w czasopismach na temat „LSRC”
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Seo, Jeong-Woo, Ki-Hyo Jang, Soon Ah Kang, Ki-Bang Song, Eun Kyung Jang, Buem-Seek Park, Chul Ho Kim i Sang-Ki Rhee. "Molecular Characterization of the Growth Phase-Dependent Expression of the lsrA Gene, Encoding Levansucrase of Rahnella aquatilis". Journal of Bacteriology 184, nr 21 (1.11.2002): 5862–70. http://dx.doi.org/10.1128/jb.184.21.5862-5870.2002.
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ABSTRACT Expression of the lsrA gene from Rahnella aquatilis, encoding levansucrase, is tightly regulated by the growth phase of the host cell; low-level expression was observed in the early phase of cell growth, but expression was significantly stimulated in the late phase. Northern blot analysis revealed that regulation occurred at the level of transcription. The promoter region was identified by primer extension analysis. Two opposite genetic elements that participate in the regulation of lsrA expression were identified upstream of the lsrA gene: the lsrS gene and the lsrR region. The lsrS gene encodes a protein consisting of 70 amino acid residues (M r, 8,075), which positively activated lsrA expression approximately 20-fold in a growth phase-dependent fashion. The cis-acting lsrR region, which repressed lsrA expression about 10-fold, was further narrowed to two DNA regions by deletion analysis. The concerted action of two opposite regulatory functions resulted in the growth phase-dependent activation of gene expression in Escherichia coli independent of the stationary sigma factor σS.
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Pleasance, Pascoe, Hazel Genn, Nigel J. Balmer, Alexy Buck i Aoife O'Grady. "Causes of Action: First Findings of the LSRC Periodic Survey". Journal of Law and Society 30, nr 1 (marzec 2003): 11–30. http://dx.doi.org/10.1111/1467-6478.00243.
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Li, Jun, Can Attila, Liang Wang, Thomas K. Wood, James J. Valdes i William E. Bentley. "Quorum Sensing in Escherichia coli Is Signaled by AI-2/LsrR: Effects on Small RNA and Biofilm Architecture". Journal of Bacteriology 189, nr 16 (8.06.2007): 6011–20. http://dx.doi.org/10.1128/jb.00014-07.
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ABSTRACT The regulatory network for the uptake of Escherichia coli autoinducer 2 (AI-2) is comprised of a transporter complex, LsrABCD; its repressor, LsrR; and a cognate signal kinase, LsrK. This network is an integral part of the AI-2 quorum-sensing (QS) system. Because LsrR and LsrK directly regulate AI-2 uptake, we hypothesized that they might play a wider role in regulating other QS-related cellular functions. In this study, we characterized physiological changes due to the genomic deletion of lsrR and lsrK. We discovered that many genes were coregulated by lsrK and lsrR but in a distinctly different manner than that for the lsr operon (where LsrR serves as a repressor that is derepressed by the binding of phospho-AI-2 to the LsrR protein). An extended model for AI-2 signaling that is consistent with all current data on AI-2, LuxS, and the LuxS regulon is proposed. Additionally, we found that both the quantity and architecture of biofilms were regulated by this distinct mechanism, as lsrK and lsrR knockouts behaved identically. Similar biofilm architectures probably resulted from the concerted response of a set of genes including flu and wza, the expression of which is influenced by lsrRK. We also found for the first time that the generation of several small RNAs (including DsrA, which was previously linked to QS systems in Vibrio harveyi) was affected by LsrR. Our results suggest that AI-2 is indeed a QS signal in E. coli, especially when it acts through the transcriptional regulator LsrR.
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Ha, Jung-Hye, Yumi Eo, Hee-Chul Ahn i Kyoung-Seok Ryu. "Increasing the soluble expression and crystallization of theEscherichia coliquorum-sensing protein LsrK". Acta Crystallographica Section F Structural Biology Communications 73, nr 5 (26.04.2017): 253–58. http://dx.doi.org/10.1107/s2053230x1700468x.
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LsrK is one of the key components of theluxS-regulated (lsr) operon inEscherichia coliand plays an important role during the quorum-sensing (QS) process mediated by autoinducer-2 (AI-2). The AI-2 molecule is imported into the cell by the LsrACB transporter and is subsequently phosphorylated (to AI-2-P) by LsrK. AI-2-P binds to the repressor protein of thelsroperon (LsrR) and triggers various cellular responses related to QS by dissociating LsrR from the DNA. Although a large amount of purified LsrK is required for structural studies, recombinant GST-LsrK was mostly expressed in an insoluble form. To enhance the soluble expression of LsrK, an attempt was made to increase the expression of the cellular chaperone proteins that are well known to support proper protein folding. TransformedE. coliwas cultured in high-salt LB medium and heat shock was applied prior to subsequent IPTG induction at 20°C. These procedures increased the yield of purified LsrK by about tenfold compared with standard IPTG induction at 20°C. The expressed LsrK was readily purified by GST-affinity chromatography. Crystals of LsrK were grown by the hanging-drop vapour-diffusion method. The X-ray diffraction data of the crystal were processed in a primitive hexagonal space group to 2.9 Å resolution.
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Huang, Chao-Jen, Yan-Jiun Lai, Yu-Jheng Ou Yang, Hung-Wei Chen, Chun-Chieh Kuo, Ke-Horng Chen, Ying-Hsi Lin, Shian-Ru Lin i Tsung-Yen Tsai. "A 4.2 nW and 18 ppm/°C Temperature Coefficient Leakage-Based Square Root Compensation (LSRC) CMOS Voltage Reference". IEEE Transactions on Circuits and Systems II: Express Briefs 66, nr 5 (maj 2019): 728–32. http://dx.doi.org/10.1109/tcsii.2019.2908284.
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Yoon, Yong Sang, Seung Jin Song i Hyoun-Woo Shin. "Influence of Flow Coefficient, Stagger Angle, and Tip Clearance on Tip Vortex in Axial Compressors". Journal of Fluids Engineering 128, nr 6 (27.03.2006): 1274–80. http://dx.doi.org/10.1115/1.2354522.
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Experiments have been performed on the low speed research compressor (LSRC) at General Electric Aircraft Engines to investigate the effects of flow coefficient, stagger angle, and tip clearance on tip vortex. Time resolved casing pressure distributions over the third stage rotor have been acquired with high-frequency-response pressure transducers. Also, tip vortex strength and trajectory have been estimated from the casing pressure fluctuations which have been obtained simultaneously from various axial locations. As flow coefficient decreases, tip vortex gets strengthened and migrates upstream. The stagger angle increase weakens the tip vortex and moves it downstream slightly because the blade loading is decreased. However, tip leakage vortex is influenced mainly by tip clearance, and there exists a “critical” tip clearance which determines the type of tip vortex trajectory (“straight” or “kinked”). As predicted by others, tip vortex gets strengthened with increasing tip clearance. However, unlike the predictions, the tip vortex trajectory moves upstream with increasing tip clearance. Furthermore, with tip clearance above a “critical” value, the tip vortex trajectory is no longer straight but shows a kink in the passage.
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Wang, Liang, Jun Li, John C. March, James J. Valdes i William E. Bentley. "luxS-Dependent Gene Regulation in Escherichia coli K-12 Revealed by Genomic Expression Profiling". Journal of Bacteriology 187, nr 24 (15.12.2005): 8350–60. http://dx.doi.org/10.1128/jb.187.24.8350-8360.2005.
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ABSTRACT The bacterial quorum-sensing autoinducer 2 (AI-2) has received intense interest because the gene for its synthase, luxS, is common among a large number of bacterial species. We have identified luxS-controlled genes in Escherichia coli under two different growth conditions using DNA microarrays. Twenty-three genes were affected by luxS deletion in the presence of glucose, and 63 genes were influenced by luxS deletion in the absence of glucose. Minimal overlap among these gene sets suggests the role of luxS is condition dependent. Under the latter condition, the metE gene, the lsrACDBFG operon, and the flanking genes of the lsr operon (lsrR, lsrK, tam, and yneE) were among the most significantly induced genes by luxS. The E. coli lsr operon includes an additional gene, tam, encoding an S-adenosyl-l-methionine-dependent methyltransferase. Also, lsrR and lsrK belong to the same operon, lsrRK, which is positively regulated by the cyclic AMP receptor protein and negatively regulated by LsrR. lsrK is additionally transcribed by a promoter between lsrR and lsrK. Deletion of luxS was also shown to affect genes involved in methionine biosynthesis, methyl transfer reactions, iron uptake, and utilization of carbon. It was surprising, however, that so few genes were affected by luxS deletion in this E. coli K-12 strain under these conditions. Most of the highly induced genes are related to AI-2 production and transport. These data are consistent with the function of LuxS as an important metabolic enzyme but appear not to support the role of AI-2 as a true signal molecule for E. coli W3110 under the investigated conditions.
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Ju, Zhenzhou, Jinfang Teng, Yuchen Ma, Mingmin Zhu i Xiaoqing Qiang. "Hub clearance effect in the design space of the cantilevered stator embedded in a 4-stage low-speed research compressor". Advances in Mechanical Engineering 13, nr 8 (sierpień 2021): 168781402110371. http://dx.doi.org/10.1177/16878140211037167.
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This paper focuses on the effect of hub clearance in the design space of the highly loaded cantilevered stator. The embedded 1.5 stages of a low-speed research compressor (LSRC) were conducted with Unsteady Reynolds Average Navier-Stokes (URANS) numerical investigation, and the cantilevered stator adopts positive bowed and fore-sweep three-dimensional design. The research details that with the hub clearance increasing from 1.1% to 4.5% span, the loss coefficient and the total leakage momentum of the cantilevered stator correspond to the change of the blade loading near the hub. When designing the inlet metal angle of the rotor downstream the cantilevered stator, emphasis should be given to considering the inter-stage matching below 15% span. The mixing of leakage flow in 1.1% span clearance and 2.5% span clearance is basically completed in the S3 passage, but the mixing of leakage flow in 3.5% span clearance and 4.5% span clearance is still relatively strong downstream of S3. When calculating the relative entropy variation based on Denton’s mixing model, attention should be paid to the relationship between the leakage flow velocity affected by the hub gap and the mainstream velocity, as well as whether the mixing has been completed in the blade passage.
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Bai, Yubin, Weiwei Wang, Mengyan Shi, Xiaojuan Wei, Xuzheng Zhou, Bing Li i Jiyu Zhang. "Novel Antibiofilm Inhibitor Ginkgetin as an Antibacterial Synergist against Escherichia coli". International Journal of Molecular Sciences 23, nr 15 (8.08.2022): 8809. http://dx.doi.org/10.3390/ijms23158809.
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As an opportunistic pathogen, Escherichia coli (E. coli) forms biofilm that increases the virulence of bacteria and antibiotic resistance, posing a serious threat to human and animal health. Recently, ginkgetin (Gin) has been discovered to have antiinflammatory, antioxidant, and antitumor properties. In the present study, we evaluated the antibiofilm and antibacterial synergist of Gin against E. coli. Additionally, Alamar Blue assay combined with confocal laser scanning microscope (CLSM) and crystal violet (CV) staining was used to evaluate the effect of antibiofilm and antibacterial synergist against E. coli. Results showed that Gin reduces biofilm formation, exopolysaccharide (EPS) production, and motility against E. coli without limiting its growth and metabolic activity. Furthermore, we identified the inhibitory effect of Gin on AI-2 signaling molecule production, which showed apparent anti-quorum sensing (QS) properties. The qRT-PCR also indicated that Gin reduced the transcription of curli-related genes (csgA, csgD), flagella-formation genes (flhC, flhD, fliC, fliM), and QS-related genes (luxS, lsrB, lsrK, lsrR). Moreover, Gin showed obvious antibacterial synergism to overcome antibiotic resistance in E. coli with marketed antibiotics, including gentamicin, colistin B, and colistin E. These results suggested the potent antibiofilm and novel antibacterial synergist effect of Gin for treating E. coli infections.
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Mailach, R., I. Lehmann i K. Vogeler. "Rotating Instabilities in an Axial Compressor Originating From the Fluctuating Blade Tip Vortex". Journal of Turbomachinery 123, nr 3 (1.02.2000): 453–60. http://dx.doi.org/10.1115/1.1370160.
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Rotating instabilities (RIs) have been observed in axial flow fans and centrifugal compressors as well as in low-speed and high-speed axial compressors. They are responsible for the excitation of high amplitude rotor blade vibrations and noise generation. This flow phenomenon moves relative to the rotor blades and causes periodic vortex separations at the blade tips and an axial reversed flow through the tip clearance of the rotor blades. The paper describes experimental investigations of RIs in the Dresden Low-Speed Research Compressor (LSRC). The objective is to show that the fluctuation of the blade tip vortex is responsible for the origination of this flow phenomenon. RIs have been found at operating points near the stability limit of the compressor with relatively large tip clearance of the rotor blades. The application of time-resolving sensors in both fixed and rotating frame of reference enables a detailed description of the circumferential structure and the spatial development of this unsteady flow phenomenon, which is limited to the blade tip region. Laser-Doppler-anemometry (LDA) within the rotor blade passages and within the tip clearance as well as unsteady pressure measurements on the rotor blades show the structure of the blade tip vortex. It will be shown that the periodical interaction of the blade tip vortex of one blade with the flow at the adjacent blade is responsible for the generation of a rotating structure with high mode orders, termed a rotating instability.
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Gabanella, Francesca, Andrea Colizza, Maria Chiara Mottola, Silvia Francati, Giovanna Blaconà, Carla Petrella, Christian Barbato i in. "The RNA-Binding Protein SMN as a Novel Player in Laryngeal Squamous Cell Carcinoma". International Journal of Molecular Sciences 24, nr 2 (16.01.2023): 1794. http://dx.doi.org/10.3390/ijms24021794.
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Head and neck squamous cell carcinoma (HNSCC) arises from the mucosal epithelium in the oral cavity, pharynx, sino-nasal region, and larynx. Laryngeal squamous cell carcinoma (LSCC) represents one-third of all head and neck cancers. Dysregulated RNA-related pathways define an important molecular signature in this aggressive carcinoma. The Survival Motor Neuron (SMN) protein regulates fundamental aspects of the RNA metabolism but, curiously, its role in cancer is virtually unknown. For the first time, here, we focus on the SMN in the cancer context. We conducted a pilot study in a total of 20 patients with LSCC where the SMN was found overexpressed at both the protein and transcript levels. By a cellular model of human laryngeal carcinoma, we demonstrated that the SMN impacts cancer-relevant behaviors and perturbs key players of cell migration, invasion, and adhesion. Furthermore, in LSCC we showed a physical interaction between the SMN and the epidermal growth factor receptor (EGFR), whose overexpression is an important feature in these tumors. This study proposes the SMN protein as a novel therapeutic target in LSSC and likely in the whole spectrum of HNSCC. Overall, we provide the first analysis of the SMN in human cancer.
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Luo, Li, Shi-Yi Yao, Anke Becker, Silvia Rüberg, Guan-Qiao Yu, Jia-Bi Zhu i Hai-Ping Cheng. "Two New Sinorhizobium meliloti LysR-Type Transcriptional Regulators Required for Nodulation". Journal of Bacteriology 187, nr 13 (1.07.2005): 4562–72. http://dx.doi.org/10.1128/jb.187.13.4562-4572.2005.
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ABSTRACT The establishment of an effective nitrogen-fixing symbiosis between Sinorhizobium meliloti and its legume host alfalfa (Medicago sativa) depends on the timely expression of nodulation genes that are controlled by LysR-type regulators. Ninety putative genes coding for LysR-type transcriptional regulators were identified in the recently sequenced S. meliloti genome. All 90 putative lysR genes were mutagenized using plasmid insertions as a first step toward determining their roles in symbiosis. Two new LysR-type symbiosis regulator genes, lsrA and lsrB, were identified in the screening. Both the lsrA and lsrB genes are expressed in free-living S. meliloti cells, but they are not required for cell growth. An lsrA1 mutant was defective in symbiosis and elicited only white nodules that exhibited no nitrogenase activity. Cells of the lsrA1 mutant were recovered from the white nodules, suggesting that the lsrA1 mutant was blocked early in nodulation. An lsrB1 mutant was deficient in symbiosis and elicited a mixture of pink and white nodules on alfalfa plants. These plants exhibited lower overall nitrogenase activity than plants inoculated with the wild-type strain, which is consistent with the fact that most of the alfalfa plants inoculated with the lsrB1 mutant were short and yellow. Cells of the lsrB1 mutant were recovered from both pink and white nodules, suggesting that lsrB1 mutants could be blocked at multiple points during nodulation. The identification of two new LysR-type symbiosis transcriptional regulators provides two new avenues for understanding the complex S. meliloti-alfalfa interactions which occur during symbiosis.
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Wang, Liang, Yoshifumi Hashimoto, Chen-Yu Tsao, James J. Valdes i William E. Bentley. "Cyclic AMP (cAMP) and cAMP Receptor Protein Influence both Synthesis and Uptake of Extracellular Autoinducer 2 in Escherichia coli". Journal of Bacteriology 187, nr 6 (15.03.2005): 2066–76. http://dx.doi.org/10.1128/jb.187.6.2066-2076.2005.
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ABSTRACT Bacterial autoinducer 2 (AI-2) is proposed to be an interspecies mediator of cell-cell communication that enables cells to operate at the multicellular level. Many environmental stimuli have been shown to affect the extracellular AI-2 levels, carbon sources being among the most important. In this report, we show that both AI-2 synthesis and uptake in Escherichia coli are subject to catabolite repression through the cyclic AMP (cAMP)-CRP complex, which directly stimulates transcription of the lsr (for “luxS regulated”) operon and indirectly represses luxS expression. Specifically, cAMP-CRP is shown to bind to a CRP binding site located in the upstream region of the lsr promoter and works with the LsrR repressor to regulate AI-2 uptake. The functions of the lsr operon and its regulators, LsrR and LsrK, previously reported in Salmonella enterica serovar Typhimurium, are confirmed here for E. coli. The elucidation of cAMP-CRP involvement in E. coli autoinduction impacts many areas, including the growth of E. coli in fermentation processes.
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Xavier, Karina B., i Bonnie L. Bassler. "Regulation of Uptake and Processing of the Quorum-Sensing Autoinducer AI-2 in Escherichia coli". Journal of Bacteriology 187, nr 1 (1.01.2005): 238–48. http://dx.doi.org/10.1128/jb.187.1.238-248.2005.
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ABSTRACT AI-2 is a quorum-sensing signaling molecule proposed to be involved in interspecies communication. In Escherichia coli and Salmonella enterica serovar Typhimurium, extracellular AI-2 accumulates in exponential phase, but the amount decreases drastically upon entry into stationary phase. In S. enterica serovar Typhimurium, the reduction in activity is due to import and processing of AI-2 by the Lsr transporter. We show that the Lsr transporter is functional in E. coli, and screening for mutants defective in AI-2 internalization revealed lsrK and glpD. Unlike the wild type, lsrK and glpD mutants do not activate transcription of the lsr operon in response to AI-2. lsrK encodes the AI-2 kinase, and the lsrK mutant fails to activate lsr expression because it cannot produce phospho-AI-2, which is the lsr operon inducer. glpD encodes the glycerol-3-phosphate (G3P) dehydrogenase, which is involved in glycerol and G3P metabolism. G3P accumulates in the glpD mutant and represses lsr transcription by preventing cyclic AMP (cAMP)-catabolite activator protein (CAP)-dependent activation. Dihydroxyacetone phosphate (DHAP) also accumulates in the glpD mutant, and DHAP represses lsr transcription by a cAMP-CAP-independent mechanism involving LsrR, the lsr operon repressor. The requirement for cAMP-CAP in lsr activation explains why AI-2 persists in culture fluids of bacteria grown in media containing sugars that cause catabolite repression. These findings show that, depending on the prevailing growth conditions, the amount of time that the AI-2 signal is present and, in turn, the time that a given community of bacteria remains exposed to this signal can vary greatly.
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Valassi, Elena, Holger Franz, Thierry Brue, Richard A. Feelders, Romana Netea-Maier, Stylianos Tsagarakis, Susan M. Webb i in. "Diagnostic tests for Cushing's syndrome differ from published guidelines: data from ERCUSYN". European Journal of Endocrinology 176, nr 5 (maj 2017): 613–24. http://dx.doi.org/10.1530/eje-16-0967.
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Objective To evaluate which tests are performed to diagnose hypercortisolism in patients included in the European Registry on Cushing’s syndrome (ERCUSYN), and to examine if their use differs from the current guidelines. Patients and methods We analyzed data on the diagnostic tests performed in 1341 patients with Cushing’s syndrome (CS) who have been entered into the ERCUSYN database between January 1, 2000 and January 31, 2016 from 57 centers in 26 European countries. Sixty-seven percent had pituitary-dependent CS (PIT-CS), 24% had adrenal-dependent CS (ADR-CS), 6% had CS from an ectopic source (ECT-CS) and 3% were classified as having CS from other causes (OTH-CS). Results Of the first-line tests, urinary free cortisol (UFC) test was performed in 78% of patients, overnight 1 mg dexamethasone suppression test (DST) in 60% and late-night salivary cortisol (LSaC) in 25%. Use of LSaC increased in the last five years as compared with previous years (P < 0.01). Use of HDDST was slightly more frequent in the last 5 years as compared with previous years (P < 0.05). Of the additional tests, late-night serum cortisol (LSeC) was measured in 62% and 48-h 2 mg/day low-dose dexamethasone suppression test (LDDST) in 33% of cases. ACTH was performed in 78% of patients. LSeC and overnight 1 mg DST supported the diagnosis of both PIT-CS and ADR-CS more frequently than UFC (P < 0.05). Conclusions Use of diagnostic tests for CS varies across Europe and partly differs from the currently available guidelines. It would seem pertinent that a European consensus be established to determine the best diagnostic approach to CS, taking into account specific inter-country differences with regard to the availability of diagnostic tools.
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Yaşaroğlu, Cihat. "Teachers' Opinions on Teaching and Assessing Methods in the Life Science Curriculum in the Context of Values". European Journal of Social Sciences Education and Research 3, nr 2 (30.04.2015): 107. http://dx.doi.org/10.26417/ejser.v3i2.p107-112.
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This research aims to investigate teachers' opinions about teaching and assessing methods that predicted in Life Sciences Course Curriculum (LSCC) in accordance of value education. Survey model was used in this research to achieve this aim. The study population consisted of 155 classroom teachers who serve in city center of Bingöl province, Turkey. An assessment instrument consisting of two chapters and developed by the researcher was used to collect data. The first chapter includes personal information about participants and the second chapter includes items that try to determine recommended teaching and assessing methods in LSSC. Arithmetic means and standard deviation were used for data analysis. It was found that teachers rated teaching and assessing methods proper. It is wished that this study will be useful for teachers, curriculum development specialists and decision makers in education system.
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Carr, E., E. Gregg, R. McCool, A. Sanderson i K. Wilson. "SA42 The Proliferation of Living Systematic Reviews (LSRS) - Dead on Arrival? A Review of LSR Methodology". Value in Health 25, nr 12 (grudzień 2022): S491. http://dx.doi.org/10.1016/j.jval.2022.09.2436.
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ARNI, FAIZ, KAYLIANG ONG, SHALOM TSUR, HAIXUN WANG i CARLO ZANIOLO. "The deductive database system [Lscr ][Dscr ][Lscr ]++". Theory and Practice of Logic Programming 3, nr 1 (18.12.2002): 61–94. http://dx.doi.org/10.1017/s1471068402001515.
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This paper describes the [Lscr ][Dscr ][Lscr ]++ system and the research advances that have enabled its design and development. We begin by discussing the new nonmonotonic and nondeterministic constructs that extend the functionality of the [Lscr ][Dscr ][Lscr ]++ language, while preserving its model-theoretic and fixpoint semantics. Then, we describe the execution model and the open architecture designed to support these new constructs and to facilitate the integration with existing DBMSs and applications. Finally, we describe the lessons learned by using [Lscr ][Dscr ][Lscr ]++ on various tested applications, such as middleware and datamining.
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Tang, Tian, i Feng Zeng. "NFIB-Mediated lncRNA PVT1 Aggravates Laryngeal Squamous Cell Carcinoma Progression via the miR-1301-3p/MBNL1 Axis". Journal of Immunology Research 2021 (12.11.2021): 1–17. http://dx.doi.org/10.1155/2021/8675123.
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Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors of head and neck cancers. In the past decades, although the therapy strategies of LSCC have made considerable improvement, the terrible outcomes of LSCC still bring an enormous burden to the world health care system. Novel therapeutic targets for LSCC are urgently needed. lncRNAs exert important roles in various biological progressions, including LSCC. Here, we aimed to investigate the function of lncRNA PVT1 in LSCC progression and its underlying molecular mechanisms. By conducting multiple experiments, our results showed that lncRNA PVT1 was upregulated in LSCC cell lines and regulated LSCC cell proliferation, apoptosis, and its cell susceptibility to natural killer (NK) cells. Moreover, it was found that lncRNA PVT1 promotes MBNL1 expression to regulate LSCC cellular progression through sponging miR-1301-3p. Our study might provide novel targets for LSCC basic research or clinical management.
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Xie, Guanhua, Lin Wang, Xiangdong Wang, Lei Wang i Laurie D. DeLeve. "Isolation of periportal, midlobular, and centrilobular rat liver sinusoidal endothelial cells enables study of zonated drug toxicity". American Journal of Physiology-Gastrointestinal and Liver Physiology 299, nr 5 (listopad 2010): G1204—G1210. http://dx.doi.org/10.1152/ajpgi.00302.2010.
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Many liver sinusoidal endothelial cell (LSEC)-dependent processes, including drug-induced liver injury, ischemia-reperfusion injury, acute and chronic rejection, fibrosis, and the HELLP (hemolytic anemia, elevated liver enzymes, low platelet count) syndrome, may have a lobular distribution. Studies of the mechanism of this distribution would benefit from a reliable method to isolate LSEC populations from different regions. We established and verified a simple method to isolate periportal, midlobular, and centrilobular LSEC. Three subpopulations of LSEC were isolated by immunomagnetic separation on the basis of CD45 expression. Flow cytometry showed that 78.2 ± 2.3% of LSEC were CD45 positive and that LSEC could be divided into CD45 bright (28.6 ± 2.7% of total population), dim (49.6 ± 1.0%), and negative populations (21.8 ± 2.3%). Immunohistochemistry confirmed that in vivo expression of CD45 in LSEC had a lobular distribution with enhanced CD45 staining in periportal LSEC. Cell diameter, fenestral diameter, number of fenestrae per sieve plate and per cell, porosity, and lectin uptake were significantly different in the subpopulations, consistent with the literature. Endocytosis of low concentrations of the LSEC-specific substrate, formaldehyde-treated serum albumin, was restricted to CD45 bright and dim LSEC. Acetaminophen was more toxic to the CD45 dim and negative populations than to the CD45 bright population. In conclusion, CD45 is highly expressed in periportal LSEC, low in midlobular LSEC, and negative in centrilobular LSEC, and this provides an easy separation method to isolate LSEC from the three different hepatic regions. The LSEC subpopulations obtained by this method are adequate for functional studies and drug toxicity testing.
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Ruiz, E. Josue, Markus E. Diefenbacher, Jessica K. Nelson, Rocio Sancho, Fabio Pucci, Atanu Chakraborty, Paula Moreno i in. "LUBAC determines chemotherapy resistance in squamous cell lung cancer". Journal of Experimental Medicine 216, nr 2 (14.01.2019): 450–65. http://dx.doi.org/10.1084/jem.20180742.
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Lung squamous cell carcinoma (LSCC) and adenocarcinoma (LADC) are the most common lung cancer subtypes. Molecular targeted treatments have improved LADC patient survival but are largely ineffective in LSCC. The tumor suppressor FBW7 is commonly mutated or down-regulated in human LSCC, and oncogenic KRasG12D activation combined with Fbxw7 inactivation in mice (KF model) caused both LSCC and LADC. Lineage-tracing experiments showed that CC10+, but not basal, cells are the cells of origin of LSCC in KF mice. KF LSCC tumors recapitulated human LSCC resistance to cisplatin-based chemotherapy, and we identified LUBAC-mediated NF-κB signaling as a determinant of chemotherapy resistance in human and mouse. Inhibition of NF-κB activation using TAK1 or LUBAC inhibitors resensitized LSCC tumors to cisplatin, suggesting a future avenue for LSCC patient treatment.
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CRIPPA, D., K. SIMON i P. TRUNZ. "Markov Processes Involving q-Stirling Numbers". Combinatorics, Probability and Computing 6, nr 2 (czerwiec 1997): 165–78. http://dx.doi.org/10.1017/s0963548397002964.
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In this paper we consider the Markov process defined byP1,1=1, Pn,[lscr ]=(1−λn,[lscr ]) ·Pn−1,[lscr ] +λn,[lscr ]−1 ·Pn−1,[lscr ]−1for transition probabilities λn,[lscr ]=q[lscr ] and λn,[lscr ]=qn−1. We give closed forms for the distributions and the moments of the underlying random variables. Thereby we observe that the distributions can be easily described in terms of q-Stirling numbers of the second kind. Their occurrence in a purely time dependent Markov process allows a natural approximation for these numbers through the normal distribution. We also show that these Markov processes describe some parameters related to the study of random graphs as well as to the analysis of algorithms.
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Legault, Jean, Pierre-Luc Larouche, Isabelle Côté, Line Bouchard, André Pichette, Brian H. Robinson i Charles Morin. "Low-Concentration Methylene Blue Maintains Energy Production and Strongly Improves Survival of Leigh Syndrome French Canadian Skin Fibroblasts". Journal of Pharmacy & Pharmaceutical Sciences 14, nr 3 (2.12.2011): 438. http://dx.doi.org/10.18433/j3m01x.
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Abstract - Leigh syndrome French Canadian (LSFC) is a recessive disease caused by mutations in the LRPPRC gene (leucine-rich pentatricopeptide repeat containing protein). These mutations induce a cytochrome c oxidase (COX) deficiency resulting in episodes of acute acidotic crisis that will often lead to death. There is no effective treatment. Methylene blue (MB) is a redox dye that increases COX content and activity in vitro and in vivo suggesting that MB could prevent and treat LSFC. In this study, the protective effect of low-concentration MB was tested on two LSFC cell lines, including LSFC-F1, homozygous for the mutation A354V, and LSFC-F2 a compound heterozygous for the mutations A354V and C12775STOP. MB effect on metabolic activity was assessed on both LSFC cells in stable and acidotic conditions. For LSFC-F1, results showed that metabolic activity drastically decline after 96 hours in both conditions but not LSFC-F2 and normal cells. MB completely prevents the decrease of metabolic activity in LSFC-F1. Intracellular ATP content was also measured in both culture media. After 96 hours in acidotic medium, ATP content was almost completely depleted for both LSFC cells. Interestingly, MB completely restores ATP content in LSFC-F1 and LSFC-F2 cells. Finally, MB strongly improves the survival of both LSFC cells.
This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
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Liu, Tianyi, Shimin Zong, Yang Jiang, Rui Zhao, Jie Wang i Qingquan Hua. "Neutrophils Promote Larynx Squamous Cell Carcinoma Progression via Activating the IL-17/JAK/STAT3 Pathway". Journal of Immunology Research 2021 (13.12.2021): 1–14. http://dx.doi.org/10.1155/2021/8078646.
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Laryngeal squamous cell carcinoma (LSCC) is the main type of laryngeal cancer with poor prognosis. Incidence of LSCC increases every year, posing a great threat to human health. The underlying mechanism needs further study. Neutrophils are the most prevalent type of immune cells, which play vital roles in crosstalk between the microenvironment and cancer cells. In our study, we aim to figure out the complex regulation between neutrophils and LSCC. Our experiments showed that LSCC cells could promote the activation and mobility of neutrophils. And, in return, neutrophils enhanced the proliferation, migration, and invasion of LSCC. The subsequent results showed that IL-17 was highly expressed in neutrophil conditioned medium. Block of IL-17 could effectively inhibit the progression of LSCC induced by neutrophils. What is more, the results showed that IL-17 activated the JAK/STAT3 pathway in LSCC. Inhibition of the JAK/STAT3 pathway could significantly block neutrophil-induced LSCC progression. Our research reveals the complex interaction between neutrophils and LSCC cells, providing new ideas for the treatment of LSCC.
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Niu, Jun-Tao, Li-Jun Zhang, Yong-Wang Huang, Chao Li, Ning Jiang i Yuan-Jie Niu. "MiR-154 inhibits the growth of laryngeal squamous cell carcinoma by targeting GALNT7". Biochemistry and Cell Biology 96, nr 6 (grudzień 2018): 752–60. http://dx.doi.org/10.1139/bcb-2018-0047.
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MicroRNAs are critical regulators of the development and progression of laryngeal squamous cell carcinoma (LSCC). However, the role of microRNA-154 (miR-154) in the development and progression of LSCC has not been clarified. We found that down-regulated miR-154 expression in LSCC tissues was associated with poorer prognosis in LSCC patients. MiR-154 over-expression inhibited the proliferation, clonogenicity, and migration of LSCC cells and induced cell cycle arrest, which were reversed by miR-154 inhibition. MiR-154 targeted GALNT7 expression by reducing GALNT7-regulated luciferase activity in LSCC cells while up-regulating GALNT7 mRNA transcription in LSCC tissues and cells. GALNT7 silencing significantly attenuated the proliferation, clonogenicity, and migration of LSCC cells and induced cell cycle arrest. Finally, intravenous treatment with lentivirus for miR-154, but not scrambled control miRNA, significantly restrained the growth of implanted LSCC Hep-2 tumors and decreased the tumor mass by reducing GALNT7 expression in mice. Therefore, miR-154 may serve as a novel prognostic marker and therapeutic target for LSCC.
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Yamamoto, Takanobu, Sawako Yada, Yuji Matsuda, Hirofumi Otani, Shunji Yoshikawa, Taro Sasaoka, Yu Hatano i in. "A Novel Rotablator Technique (Low-Speed following High-Speed Rotational Atherectomy) Can Achieve Larger Lumen Gain: Evaluation Using Optimal Frequency Domain Imaging". Journal of Interventional Cardiology 2019 (20.05.2019): 1–7. http://dx.doi.org/10.1155/2019/9282876.
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Background. While the evaluation of burr speed was discussed regarding platelet aggregation, the association between platform speed and acute lumen gain of rotational atherectomy remains unknown. Methods. Through the evaluation of the potential of low-speed rotational atherectomy (LSRA) in in-vitro experiments, minimum lumen diameter (MLD) and minimum lumen area (MLA) after conventional high-speed rotational atherectomy (HSRA group) and those after LSRA following HSRA (LSRA+HSRA group) treated by 1.5 mm burrs were measured by optical frequency domain imaging (OFDI) in 30 consecutive human lesions. Results. The in-vitro experiments demonstrated that MLD and MLA after LSRA+HSRA were significantly larger (MLD: LSRA+HSRA=1.50 ±0.05 mm, HSRA= 1.43 ±0.05 mm, p=0.015; MLA: LSRA+HSRA= 1.90 ±0.17 mm2, HSRA= 1.71±0.11 mm2, and p= 0.037), requiring more crossing attempts (LSRA= 134 ±20 times, HSRA= 72 ±11 times, and p< 0.001). In human studies, there was no significance in reference vessel diameter and lesion length before the procedure between two groups. MLDs after LSRA+HSRA were significantly larger than those in HSRA (LSRA+HSRA= 1.22 ±0.16 mm, HSRA= 1.07 ±0.14 mm, and p= 0.0078), while MLAs after LSRA+HSRA tended to be larger (LSRA+HSRA= 1.79 ±0.51 mm2, HSRA= 1.55 ±0.47 mm2, and p= 0.19). There was no significance in the occurrence of in-hospital complication, including slow flow or no reflow, major dissection, and procedural myocardial infarction, between LSRA+HSRA and HSRA. Conclusions. LSRA can achieve larger lumen gain compared, whereas HSRA can pass calcified lesions easily. Combination of LSRA and HSRA is a safe and feasible strategy for severely calcified lesions in clinical practice.
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Yin, Yong, Keke Yang, Juanjuan Li, Peng Da, Zhenxin Zhang i Xiaoxia Qiu. "Interferon-induced transmembrane protein 1 (IFITM1) is essential for progression of laryngeal squamous cell carcinoma in an Osteopontin/NF-κB-dependent manner". Cancer Biomarkers 29, nr 4 (20.11.2020): 521–29. http://dx.doi.org/10.3233/cbm-201435.
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OBJECTIVE: To assess the expression levels of IFITM1 in human tissue samples and laryngeal squamous cell carcinoma (LSCC) cells, and to explore the potential mechanisms of IFITM1 in LSCC progression. METHODS: Quantitative PCR and immunohistochemical (IHC) assays were performed to detect IFITM1 expression in 62 LSCC tissues and corresponding normal tissues. We further detected the effects of IFITM1 on the proliferation, migration and invasion of LSCC cells and NF-κB signaling pathway through colony formation assay, wound healing assay and transwell assay, respectively. RESULTS: We demonstrated the possible involvement of IFITM1 in the progression of LSCC. We found the upregulated expression of IFITM1 in human LSCC tissues and cells, and analyzed the correlations between IFITM1 expression and osteopontin. Our data further confirmed that IFITM1 affected cell proliferation, migration, and invasion of LSCC cells via the regulation of NF-κB signaling pathway. CONCLUSIONS: We investigated the potential involvement of IFITM1 in the progression of LSCC, and therefore confirmed that IFITM1 was a potential therapeutic target for LSCC.
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Zhu, Yong, Yedong Mi, Zhonghua Qin, Xuewei Jiang, Yibo Shan, Kamil Kural i Guiping Yu. "Increased PPARD Expression May Play a Protective Role in Human Lung Adenocarcinoma and Squamous Cell Carcinoma". PPAR Research 2022 (15.03.2022): 1–9. http://dx.doi.org/10.1155/2022/9414524.
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Peroxisome proliferator-activated receptor-δ, encoded by gene PPARD, is overexpressed in a majority of human lung cancer subtypes, but its role in the tumor progression remains poorly understood. We have analyzed the expression of PPARD in lung adenocarcinoma (LA) and squamous cell carcinoma (LSCC) datasets. The potential roles of PPARD in the pathological development of LA and LSCC were explored through literature-based pathway analysis and pathway enrichment analysis. In all LA datasets ( N = 11 ) and in seven out of nine LSCC studies, the levels of PPARD were increased as compared to control tissues (log-fold changes were 0.37 ± 0.20 and 0.10 ± 0.37 for LA and LSCC, respectively). On average, the expression levels of PPARD in LA were higher than those in LSCC ( p = 0.036 ). Pathway analysis showed that the overexpression of PPARD might play both positive and negative roles in the development of both LA and LSCC. Specifically, PPARD inhibits seven LSCC promoters and seven LA promoters and activates one LSCC inhibitor and another LA inhibitor. However, PPARD also activates six and one promoters of LA and LSCC, respectively, which would facilitate the development of LA/LSCC. Our results suggested a mixed role of PPARD in LA/LSCC, which may add new insights into the understanding of the PPARD-lung cancer relationship.
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Liutkeviciene, Rasa, Justina Auzelyte, Vykintas Liutkevicius, Alvita Vilkeviciute, Greta Gedvilaite, Paulius Vaiciulis i Virgilijus Uloza. "The Role of ApoE Serum Levels and ApoE Gene Polymorphisms in Patients with Laryngeal Squamous Cell Carcinoma". Biomolecules 12, nr 8 (22.07.2022): 1013. http://dx.doi.org/10.3390/biom12081013.
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Recent studies have revealed that the inflammatory ApoE effect may play a significant role in various cancer development. However, this effect has still not been analyzed in patients with laryngeal squamous cell carcinoma (LSCC). In the present study, we evaluated two single nucleotide polymorphisms (SNPs) of ApoE (rs7412 and rs429358) and determined their associations with LSCC development and the LSCC patients’ five-year survival rate. Additionally, we analyzed serum ApoE levels using an enzyme-linked immunosorbent assay. A total of 602 subjects (291 histologically verified LSCC patients and 311 healthy controls) were involved in this study. The genotyping was carried out using the real-time PCR. We revealed that ApoE ε3/ε3 was associated with a 1.7-fold higher probability of developing LSCC (p = 0.001), with 1.7-fold increased odds of developing LSCC without metastasis to the lymph nodes (p = 0.002) and with a 2.0-fold increased odds of developing well-differentiated LSCC (p = 0.008), as well as 1.6-fold increased odds of developing poorly differentiated LSCC development (p = 0.012). The ApoE ε2/ε4 and ε3/ε4 genotypes were associated with a 2.9-fold and 1.5-fold decrease in the likelihood of developing LSCC (p = 0.042; p = 0.037, respectively). ApoE ε3/ε4 was found associated with a 2.4-fold decreased likelihood of developing well-differentiated LSCC (p = 0.013). Conclusion: ApoE ε2/ε4 and ε3/ε4 were found to play a protective role in LSCC development, while ApoE ε3/ε3 may have a risk position in LSCC development.
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Wang, Nan, Xuanyu Huang i Jinsheng Cheng. "BIRC5 promotes cancer progression and predicts prognosis in laryngeal squamous cell carcinoma". PeerJ 10 (1.02.2022): e12871. http://dx.doi.org/10.7717/peerj.12871.
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Background Laryngeal squamous cell carcinoma (LSCC) remains one of the most common respiratory tumors worldwide. Baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) is a member of the inhibitor-of-apoptosis protein family. BIRC5 plays an important role in various types of cell proliferation, differentiation, migration and invasion. However, the specific role of BIRC5 in LSCC remains unclear. Methods To provide a prognostic biomarker for LSCC, we screened the prognostic genes of LSCC via bioinformatics. PPI network and KEGG pathways were used to select hub genes. Clinical prognoses were performed using a Kaplan–Meier plotter and Cox proportional-hazard analysis. BIRC5 expression in LSCC tissues and cell lines were detected by RT-PCR, Western blot and Immunohistochemistry (IHC). Cell proliferation, cell cycle and cell apoptosis were detected with Cell Counting Kit-8 (CCK-8) and Flow Cytometry assay, respectively. Results Here, BIRC5 was strongly correlated with higher tumor grade and differentiation. BIRC5 was highly expressed in LSCC tissues when compared with normal tissues and increased expression of BIRC5 was associated with overall survival in LSCC patients. The suppression of BIRC5 induced cell apoptosis and cell cycle arrest, thereby inhibiting the proliferation of LSCC cells. The survival analysis confirmed that higher level of BIRC5 expression predicted poor prognosis of LSCC patients. BIRC5 may act as an oncogene of LSCC development and was suggested as a promising prognostic biomarker for LSCC.
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Gordon, Blair R. G., Robin Imperial, Linru Wang, William Wiley Navarre i Jun Liu. "Lsr2 of Mycobacterium Represents a Novel Class of H-NS-Like Proteins". Journal of Bacteriology 190, nr 21 (5.09.2008): 7052–59. http://dx.doi.org/10.1128/jb.00733-08.
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ABSTRACT Lsr2 is a small, basic protein present in Mycobacterium and related actinomycetes. Our previous in vitro biochemical studies showed that Lsr2 is a DNA-bridging protein, a property shared by H-NS-like proteins in gram-negative bacteria. Here we present in vivo evidence based on genetic complementation experiments that Lsr2 is a functional analog of H-NS, the first such protein identified in gram-positive bacteria. We show that lsr2 can complement the phenotypes related to hns mutations in Escherichia coli, including β-glucoside utilization, mucoidy, motility, and hemolytic activity. We also show that Lsr2 binds specifically to H-NS-regulated genes and the repression of hlyE by Lsr2 can be partially eliminated by overexpression of slyA, suggesting that the molecular mechanisms of Lsr2 repression and depression are similar to those of H-NS. The functional equivalence of these two proteins is further supported by the ability of hns to complement the lsr2 phenotype in Mycobacterium smegmatis. Taken together, our results demonstrate unequivocally that Lsr2 is an H-NS-like protein.
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Kwak, Sang Hyun, Min Ki Kim, Sung Huhn Kim i Jinsei Jung. "Audiological and Vestibular Functions in Patients With Lateral Semicircular Canal Dysplasia and Aplasia". Clinical and Experimental Otorhinolaryngology 13, nr 3 (1.08.2020): 255–60. http://dx.doi.org/10.21053/ceo.2019.01053.
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Objectives. The aim of the present study was to evaluate audiologic and vestibular functions in patients with lateral semicircular canal (LSCC) dysplasia/aplasia.Methods. We conducted a retrospective study of a patients with LSCC dysplasia and aplasia at tertiary referral center. The subjects included 15 patients with LSCC dysplasia or aplasia, with or without combined inner ear anomalies. Medical history, temporal bone computed tomography scans, pure-tone audiograms, and vestibular function test results were analyzed.Results. LSCC anomaly was identified in 15 patients (20 ears). Nine patients had unilateral LSCC dysplasia only and showed a mean pure-tone average of 45.5±28.7 dB, while three patients (33.3%) among them had normal hearing. Six patients had bilateral LSCC dysplasia/aplasia combined with other inner ear anomalies and profound bilateral hearing loss. Notably, only four out of 15 patients (26.7%) had dizziness symptoms. On caloric test, patients with isolated LSCC dysplasia showed a 51.8%±29.3% level of canal paresis (eight out of nine patients showed anomalies), whereas patients with bilateral LSCC dysplasia/aplasia presented bilateral vestibular loss. One patient with isolated LSCC underwent video-head impulse test; horizontal canal gain decreased to 0.62 (17% asymmetry) and anterior canal gain was 0.45 (52.6% asymmetry), whereas posterior canal gain was normal.Conclusion. Bilateral LSCC dysplasia/aplasia is comorbid with other inner ear anomalies and presents as profound bilateral hearing loss and vestibulopathy. In contrast, isolated unilateral LSCC dysplasia presents as ipsilateral horizontal canal paresis. Hearing function in isolated LSCC dysplasia is usually, but not always, impaired with varying severity.
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Ma, Jinhua, Xiaodong Hu, Baoqiang Dai, Qiang Wang i Hongqin Wang. "Prediction of the mechanism of miRNAs in laryngeal squamous cell carcinoma based on the miRNA-mRNA regulatory network". PeerJ 9 (24.08.2021): e12075. http://dx.doi.org/10.7717/peerj.12075.
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In this study, a bioinformatics analysis is conducted to screen differentially expressed miRNAs and mRNAs in laryngeal squamous cell carcinoma (LSCC). Based on this information, we explored the possible roles of miRNAs in the pathogenesis of LSCC. The RNA-Seq data from 79 laryngeal cancer samples in the Gene Expression Omnibus (GEO) database were sorted. Differentially expressed miRNAs and mRNAs in LSCC are screened using the PERL programming language, and it was analysed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The miRNA-mRNA regulatory network of LSCC is constructed using Cytoscape software. Then, quantitative real-time PCR (QRT- PCR), Cell Counting Kit-8 (CCK8) and flow cytometry analysis we are used to further validate key miRNAs. We identified 99 differentially expressed miRNAs and 2,758 differentially expressed mRNAs in LSCC tissues from the GEO database. Four more important miRNAs displaying a high degree of connectivity are selected, these results suggest that they play an important role in the pathogenesis of LSCC. As shown in the present study, we identified specific miRNA-mRNA networks associated with the occurrence and development of LSCC through bioinformatics analysis. We found a miRNA molecule closely related to LSCC based on miRNA-mRNA network: miR-140-3p was down-regulated in LSCC. In addition, the potential antitumor effect of miR-140-3p in LSCC was verified in the experiment, and it was proved that overexpression of miR-140-3p could inhibit the proliferation of LSCC cells and promote cell apoptosis, suggesting that miR-140-3p may be a potential tumor marker in LSCC.
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Zhang, Yi, Kaisai Tian, Enhui Zhou, Xiaocheng Xue, Shiling Yan, Yixin Chen, Peipei Qiao, Liyun Yang i Xiaoping Chen. "hsa_circ_0023305 Enhances Laryngeal Squamous Cell Carcinoma Progression and Modulates TRPM7 via miR-218-5p Sponging". BioMed Research International 2021 (2.12.2021): 1–11. http://dx.doi.org/10.1155/2021/9968499.
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Recently, circular RNAs have been shown to function as critical regulators of many human cancers. However, the circRNA mechanism in laryngeal squamous cell carcinoma (LSCC) remains elusive. Recent investigations using bioinformatics analysis revealed high expression of hsa_circ_0023305 in LSCC tissues compared to normal tissues. Furthermore, we discovered that hsa_circ_0023305 expression level was positively correlated to tumor/node/metastasis (TNM) stage as well as lymph node metastasis in LSCC. Moreover, higher hsa_circ_0023305 levels were correlated to poorer LSCC patient outcomes. Knockdown of hsa_circ_0023305 significantly inhibited LSCC cell proliferation, invasion, and migration abilities. Our team validated that hsa_circ_0023305 functioned as a miR-218-5p sponge from a mechanistic perspective, targeting the melastatin-related transient receptor potential 7 (TRPM7) in LSCC cells. TRPM7 regulates a nonselective cation channel and promotes cancer proliferation and metastasis. Our data demonstrated that miR-218-5p was downregulated in LSCC and that miR-218-5p upregulation repressed LSCC proliferation and invasion both in vivo and in vitro. Additionally, we found that hsa_circ_0023305-mediated upregulation of TRPM7 inhibited miR-218-5p and contributed to LSCC migration, proliferation, and invasion. In summary, these data propose a new mechanism by which the hsa_circ_0023305/miR-218-5p/TRPM7 network enhances LSCC progression.
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Shi, Shunbin, Guiping Yu, Bin Huang, Yedong Mi, Yan Kang i Julia Pia Simon. "PPARG Could Work as a Valid Therapeutic Strategy for the Treatment of Lung Squamous Cell Carcinoma". PPAR Research 2020 (1.06.2020): 1–9. http://dx.doi.org/10.1155/2020/2510951.
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Previous studies showed that PPAR-gamma (PPARG) ligands might serve as potential therapeutic agents for nonsmall cell lung cancer (NSCLC). However, a few studies reported the specific relationship between PPARG and lung squamous cell carcinoma (LSCC). Here, we made an effort to explore the relationship between PPARG and LSCC. First, we used mega-analysis and partial mega-analysis to analyze the effects of PPARG on LSCC by using 12 independent LSCC expression datasets (285 healthy controls and 375 LSCC cases). Then, literature-based molecular pathways between PPARG and LSCC were established. After that, a gene set enrichment analysis (GSEA) was conducted to study the functionalities of PPARG and PPARG-driven triggers within the molecular pathways. Finally, another mega-analysis was constructed to test the expression changes of PPARG and its driven targets. The partial mega-analysis showed a significant downregulated expression of PPARG in LSCC (LFC=−1.08, p value=0.00073). Twelve diagnostic markers and four prognostic markers were identified within multiple PPARG-LSCC regulatory pathways. Our results suggested that the activation of PPARG expression may inhibit the development and progression of LSCC through the regulation of LSCC upstream regulators and downstream marker genes, which were involved in tumor cell proliferation and protein polyubiquitination/ubiquitination.
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Yin, Chengyi, Bingliang Ma, Xilin Zhang, Longjiang Lan, Gang Ren, Jue Xu i Jianqiu Wang. "Overexpression of Laminin 5γ2 Chain Correlates with Tumor Cell Proliferation, Invasion, and Poor Prognosis in Laryngeal Squamous Cell Carcinoma". Journal of Oncology 2022 (15.10.2022): 1–11. http://dx.doi.org/10.1155/2022/7248064.
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Objective. Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor. Laminin 5γ2 chain (LAMC2) was reported to be associated with tumorigenesis. This study explored the role of LAMC2 on LSCC progression by regulating the integrinβ1/FAK/Src/AKT pathway. Methods. The level of LAMC2 in 46 LSCC patients was detected by qRT-PCR and western blot. Then the relationship between LAMC2 expression and LSCC malignancy as well as prognosis was analyzed, and the effect of LAMC2 expression on LSCC patient survival was also analyzed using the Kaplan–Meier survival curves. Afterwards, the LSCC cells were transfected with LAMC2 overexpression and knockdown vectors, the effect of LAMC2 on LSCC cell viability, proliferation ability, cell cycle, cell migration, and invasion were detected by CCK-8, colony formation, flow cytometry, wound healing, and Transwell assays. The expression of EMT-related biomarkers and integrin β1/FAK/Src/AKT signaling-related proteins was detected by western blot. Moreover, the effect of LAMC2 on LSCC tumor growth was evaluated by in vivo xenograft experiments and western blot. Results. LAMC2 was expressed at high level in LSCC tissues and associated with poor prognosis. LAMC2 overexpression increased TU177 cell viability, proliferation ability, promoted cell cycle, cell migration, and invasion capacity. The expression of N-cadherin, vimentin, and integrinβ1/FAK/Src/AKT related proteins was increased, while the expression of E-cadherin protein was decreased. When the LAMC2 knockdown in AMC-HN-8 cells had opposite effects. Furthermore, shLAMC2 decreased tumor volume and the expression of LAMC2, Ki-67 and integrinβ1, but increased the expression of E-cadherin in LSCC tumor-bearing mice. Conclusion. The findings suggested that LAMC2 was overexpressed in LSCC and correlated with poor prognosis. LAMC2 knockdown inhibited LSCC progression by regulating the integrinβ1/FAK/Src/AKT signaling pathway. Therefore, LAMC2 could be a target for LSCC therapy.
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Yuan, Xiaowei, Qinhua Shen i Wenxue Ma. "Long Noncoding RNA Hotair Promotes the Progression and Immune Escape in Laryngeal Squamous Cell Carcinoma through MicroRNA-30a/GRP78/PD-L1 Axis". Journal of Immunology Research 2022 (4.04.2022): 1–13. http://dx.doi.org/10.1155/2022/5141426.
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Homeobox (HOX) transcript antisense RNA (Hotair) is elevated in many cancers significantly. However, the oncogenic role of Hotair in human laryngeal squamous cell carcinoma (LSCC) is still unknown. Thus, we explored the expression profile of Hotair and its function in LSCC. We observed high expression levels of Hotair in six LSCC cell lines compared to the human nasopharyngeal epithelial cell line. Knockdown of Hotair inhibited proliferation and enhanced apoptosis of Tu212 and Hep-2 cell lines in vitro. Moreover, the overexpression of hsa-miR-30a-5p inhibited the expression of GRP78 and PD-L1, but Hotair overexpression in LSCC cells rescues both proteins. Furthermore, the impacts of hsa-miR-30a-5p upregulation on the apoptosis and proliferation of LSCC cells were rescued by overexpression of Hotair. Finally, we combined si-Hotair and a VEGF inhibitor to treat LSCC cells in vitro or in vivo and surprisingly observed a significant inhibition of LSCC growth. In summary, these results indicate that Hotair displays an oncogenic role in both malignancy and immune escape in LSCC related to hsa-miR-30a-5p/GRP78/PD-L1 signaling. Therefore, Hotair may be a potential target for treating LSCC.
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Yang, ChunPing, ShuFeng Gao, HaiZhen Zhang, Lian Xu, JianGuo Liu, Meiqun Wang i ShaoRong Zhang. "CD47 is a Potential Target for the Treatment of Laryngeal Squamous Cell Carcinoma". Cellular Physiology and Biochemistry 40, nr 1-2 (2016): 126–36. http://dx.doi.org/10.1159/000452530.
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Background/Aims: This study aims to investigate the effect of CD47 on the development of laryngeal squamous cell carcinoma (LSCC) and the therapeutic potential of monoclonal antibody against CD47 and its ligand SIRPα in the treatment of LSCC. Methods: We firstly detected the expressions of CD47 mRNA and protein in LSCC and para-carcinoma tissues, introduced the most efficient CD47siRNA sequence into LSCC cells by lentiviral transfection and employed three monoclonal antibodies to evaluate their anti-LSCC effects in vitro and in vivo. Results: We observed that the mRNA and protein expressions of CD47 in LSCC tissue had significant increase in LSCC tissues compared with those in para-carcinoma tissue (p < 0.05). After the treatments of three monoclonal antibodies, i.e. anti-SIRPα, anti-CD47 BRIC126, anti-CD47 B6H12.2, in rats transfected with Hep-2 cell, it has been showed that the mRNA and protein expressions of CD47 in LSCC tissue decreased, macrophage efficiency was promoted when anti-SIRPα and/or CD47siRNA were used, the amounts, viabilities and expressions of CD47 protein of tumor cell were significantly inhibited. Additionally, combined use of CD47siRNA and anti-SIRPα seemed more efficient than solo use of CD47siRNA/anti-SIRPα. Conclusion: The results suggested a critical role of CD47 in LSCC development and the promising treatment of antiCD47/SIRPα and/or CD47siRNA in LSCC.
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Tieu, Ashley, Benjamin Chaigne, Bertrand Dunogué, Jérémie Dion, Alexis Régent, Marion Casadevall, Pascal Cohen i in. "Autoantibodies versus Skin Fibrosis Extent in Systemic Sclerosis: A Case-Control Study of Inverted Phenotypes". Diagnostics 12, nr 5 (24.04.2022): 1067. http://dx.doi.org/10.3390/diagnostics12051067.
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Objective: to describe the prevalences, characteristics, and survivals of patients with anti-topoisomerase 1 antibodies (ATA) and limited cutaneous systemic sclerosis (lSSc) and anti-centromere antibodies (ACA) and diffuse cutaneous systemic sclerosis (dSSc). Methods: patients with ATA lSSc or with ACA dSSc were included in a case-control retrospective study. Results: In our cohort of scleroderma, the prevalence of ACA dSSc and ATA lSSc was 1.1% (12/1040) and 8.9% (93/1040), respectively. ACA dSSc patients had less interstitial lung disease (ILD) (5 (41.7) vs. 74 (79.6); p < 0.01), more cardiac involvement, and more muscle involvement (3 (25) vs. 4 (4.3); p = 0.03 and 4 (33.3) vs. 4 (7.5); p = 0.02,) than ATA dSSc patients. ATA lSSc patients had a higher modified Rodnan skin score than ACA lSSc patients (4 [2–7.5] vs. 2 [0–5]; p < 0.01) and less cardiac or muscle involvement than ATA dSSc patients (6 (6.5) vs. 19 (20.4%); p < 0.01 and 15 (16.1) vs. 54 (58.1); p < 0.0001, respectively). The cumulative 5-year survival rate was 71% in ACA dSSc patients, 95% in ATA lSSc patients, 84% in ACA lSSc patients, and 66% in ATA dSSc patients (p < 0.0001). Conclusion: ATA lSSc and ACA dSSc have specific characteristics when compared to ATA dSSc or ACA lSSc. ATA lSSc patients have more ILD than ACA lSSc patients, and ATA dSSc patients have the worst prognosis. Overall, inverted phenotypes show the value of a patient assessment combining antibody and skin subset and should be considered as a separate group.
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Cardier, Jose E., i Gonzalo Luna. "Crosstalk between Murine Liver Sinusoidal Endothelial Cells (LSEC) and Hematopoietic Stem Cells during In Vitro Hematopoiesis." Blood 108, nr 11 (16.11.2006): 4245. http://dx.doi.org/10.1182/blood.v108.11.4245.4245.
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Abstract Crosstalk between murine liver sinusoidal endothelial cells (LSEC) and hematopoietic stem cells during in vitro hematopoiesis. G. Luna, J. E. Cardier. Laboratorio de Patologia Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas (IVIC). Apartado 21827, Caracas, Venezuela We have showed that at the liver there is a specific hematopoietic microenvironment, constituted by the liver sinusoid endothelial cells (LSEC), which are capable to support, in vitro and in vivo, not only the proliferation but also the differentiation and survival of hematopoietic stem cells (HSC). The ability of LSEC to support hematopoiesis could be related to specific hematopoietic molecules expressed by these cells. In this study, we investigate the expression of some cell adhesion molecules (VCAM-1, ICAM-1, and the integrin a4b1 ), and early acting hematopoietic cytokines (IL-6 and GM-CSF), on LSEC cocultured with HSC. The expression of VCAM-1, ICAM-1, α4β1, IL6 and GM-SCF was increased on LSEC cocultured with HSC. In contrast, a significant decrease in the expression of IL-6 and GM-CSF in the HSC derived from the same cocultures was observed. The blockade of VCAM-1 on LSEC reduced significantly the adhesion of HSC to LSEC monolayers, suggesting that this molecule is involved in the binding of HSC to LSEC microenvironments. There were not changes in the expression of the molecules evaluated when the LSEC and HSC were co-cultured in non-contact conditions, suggesting that soluble factors do not participate in regulating the expression of these molecules. Our data shows that during in vitro hematopoiesis, LSEC are activated to express molecules associated with the hematopoiesis process. LSEC activation is regulated by the contact between these cells and HSC. By expressing critical hematopoietic microenvironment molecules, LSEC may regulate the proliferation and differentiation of HSC, during liver extramedullary hematopoiesis.
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Ran, Dan, Isabel Taubert, Volker Eckstein, Frauke Bellos, Patrick Wuchter, Rainer Saffrich, Mario Schubert i Anthony D. Ho. "Frequency of Leukemia Stem Cell Candidates Predicts Refractoriness to Conventional Chemotherapy and Adverse Clinical Outcome". Blood 116, nr 21 (19.11.2010): 2160. http://dx.doi.org/10.1182/blood.v116.21.2160.2160.
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Abstract Abstract 2160 We have shown that leukemia stem cells candidates (LSCC) can be prospectively identified by high activity of aldehyde dehydrogenase (ALDHbr) and expression of CD34 among the leukemia blasts from the marrow of patients with AML. In this study we have examined the relationship between the frequency of LSCC at diagnosis with persistence of leukemia blasts after induction chemotherapy as well as with long-term clinical outcome. Using single cell sorting, we have further separated subsets among the LSCC and correlated their individual functional properties with the respective marker constellation. The percentage of LSCC in 101 patients ranged from 0.01% to 12.90% with a median of 0.51%. Frequencies of LSCC among the leukemia blasts at diagnosis correlated significantly with the persistence of leukemia after the first induction chemotherapy (n=79, Spearman R=0.7797, P<0.0001). During the observation period of 24 months, 21 of 60 patients with high levels of LSCC died as compared to 7 of 41 patients with low levels of LSCC (p=0.029). The overall survival (OS) probability for the patients with high levels of LSCC was significantly worse (p=0.05) than in those with low LSCC. Characterization of these LSCC at a single cell level showed that a varying proportion, i.e. 15% to 78% of their progeny cells demonstrated the same chromosomal aberrations as the original leukemia population, indicating the presence of residual normal HSC. Thus high frequencies of LSCC at the time of diagnosis predict persistence of leukemia blasts, failure to achieve CR within the first cycle and poor overall clinical outcome. Our prospective separation of LSCC permits precise characterization of the biological properties of the subsets of stem cell candidates in human AML. Disclosures: Ho: Genzyme: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees.
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Shi, Fang, i Ling Li. "Phosphatidylinositol 3-Kinase/Protein Kinase B/Mammalian Target of the Rapamycin Pathway-Related Protein Expression in Lung Squamous Cell Carcinoma and Its Correlation with Lymph Node Metastasis". Journal of Oncology 2022 (23.08.2022): 1–7. http://dx.doi.org/10.1155/2022/4537256.
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The targeted therapy of lung squamous cell carcinoma (LSCC), a pathological type of non-small-cell lung cancer, is relatively lacking by contrast with lung adenocarcinoma. The overexpression or inhibition of intracellular signaling pathways leads to disease. To evaluate genes for a targeted therapy in LSCC, we analyzed PI3K pathway components in LSCC tissues and found elevated PI3K levels in LSCC tissues compared with adjacent counterparts. A comparison of PI3K levels in tissues with and without metastasis revealed that the PI3K pathway activity was greatly increased in metastatic tissues. Our findings suggest that the metastasis of cancer cells in patients with LSCC is closely related to the overexpression of PI3K pathway components in cancer tissues. We performed in vitro cell culture experiments and found that inhibition of PI3K activity decreased proliferation and increased apoptosis in H520 cells, suggesting that PI3K pathway inhibition limits LSCC cell proliferation. We hypothesize that LSCC metastasis is related to the overexpression of PI3K pathway components and inhibiting this pathway may help reduce the risk of lymph node metastasis in LSCC patients.
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Yang, Zhendong, Jianping Jin i Tao Chang. "CircPTK2 (hsa_circ_0003221) Contributes to Laryngeal Squamous Cell Carcinoma by the miR-1278/YAP1 Axis". Journal of Oncology 2021 (13.10.2021): 1–22. http://dx.doi.org/10.1155/2021/2408384.
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Laryngeal cancer accounts for 20% of all head and neck malignancies. Laryngeal squamous cell carcinoma (LSCC) is the most common type of laryngeal cancer and is characterized by squamous differentiation, a high mortality rate, and poor prognosis. Accumulating studies have indicated that circular RNAs (circRNAs) are critical regulators in many cancers. CircPTK2 exerts an important regulatory role in several cancers. In this study, we aimed to elucidate the function of circPTK2 (hsa_circ_0003221) in LSCC. Through a series of investigations, we discovered that circPTK2 was significantly upregulated in LSCC tissues cells. Functionally, cell counting kit-8 (CCK-8) and flow cytometry analyses revealed that knockdown of circPTK2 suppressed LSCC cell viability and the cell cycle while promoting cell apoptosis. Notably, silencing circPTK2 inhibited tumor growth in vivo. Mechanistically, circPTK2 functioned as a molecular sponge of miR-1278 to upregulate YAP1 expression in LSCC cells. Moreover, YAP1 knockdown inhibited malignant phenotypes of LSCC cells. The rescue experiments showed that YAP1 overexpression reversed the effects of circPTK2 on LSCC cells. Therefore, we concluded that circPTK2 facilitates LSCC progression through the miR-1278/YAP1 axis.
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Furuta, Kunimaro, Qianqian Guo, Petra Hirsova i Samar H. Ibrahim. "Emerging Roles of Liver Sinusoidal Endothelial Cells in Nonalcoholic Steatohepatitis". Biology 9, nr 11 (12.11.2020): 395. http://dx.doi.org/10.3390/biology9110395.
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Nonalcoholic steatohepatitis (NASH) has become a growing public health problem worldwide, yet its pathophysiology remains unclear. Liver sinusoidal endothelial cells (LSEC) have unique morphology and function, and play a critical role in liver homeostasis. Emerging literature implicates LSEC in many pathological processes in the liver, including metabolic dysregulation, inflammation, angiogenesis, and carcinogenesis. In this review, we highlight the current knowledge of the role of LSEC in each of the progressive phases of NASH pathophysiology (steatosis, inflammation, fibrosis, and the development of hepatocellular carcinoma). We discuss processes that have important roles in NASH progression including the detrimental transformation of LSEC called “capillarization”, production of inflammatory and profibrogenic mediators by LSEC as well as LSEC-mediated angiogenesis. The current review has a special emphasis on LSEC adhesion molecules, and their key role in the inflammatory response in NASH. Moreover, we discuss the pathogenic role of extracellular vesicles and their bioactive cargos in liver intercellular communication, inflammation, and fibrosis. Finally, we highlight LSEC-adhesion molecules and derived bioactive product as potential therapeutic targets for human NASH.
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Lu, Miaolong, Wei Chen, Wei Zhuang i Xianquan Zhan. "Label-free quantitative identification of abnormally ubiquitinated proteins as useful biomarkers for human lung squamous cell carcinomas". EPMA Journal 11, nr 1 (4.01.2020): 73–94. http://dx.doi.org/10.1007/s13167-019-00197-8.
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Abstract Background Ubiquitination is an important molecular event in lung squamous cell carcinoma (LSCC), which currently is mainly studied in nonsmall cell lung carcinoma cell models but lacking of ubiquitination studies on LSCC tissues. Here, we presented the ubiquitinated protein profiles of LSCC tissues to explore ubiquitination-involved molecular network alterations and identify abnormally ubiquitinated proteins as useful biomarkers for predictive, preventive, and personalized medicine (PPPM) in LSCC. Methods Anti-ubiquitin antibody-based enrichment coupled with LC-MS/MS was used to identify differentially ubiquitinated proteins (DUPs) between LSCC and control tissues, followed by integrative omics analyses to identify abnormally ubiquitinated protein biomarkers for LSCC. Results Totally, 400 DUPs with 654 ubiquitination sites were identified,, and motifs A-X (1/2/3)-K* were prone to be ubiquitinated in LSCC tissues. Those DUPs were involved in multiple molecular network systems, including the ubiquitin–proteasome system (UPS), cell metabolism, cell adhesion, and signal transduction. Totally, 44 hub molecules were revealed by protein–protein interaction network analysis, followed by survival analysis in TCGA database (494 LSCC patients and 20,530 genes) to obtain 18 prognosis-related mRNAs, of which the highly expressed mRNAs VIM and IGF1R were correlated with poorer prognosis, while the highly expressed mRNA ABCC1 was correlated with better prognosis. VIM-encoded protein vimentin and ABCC1-encoded protein MRP1 were increased in LSCC, which were all associated with poor prognosis. Proteasome-inhibited experiments demonstrated that vimentin and MRP1 were degraded through UPS. Quantitative ubiquitinomics found ubiquitination level was decreased in vimentin and increased in MRP1 in LSCC. These findings showed that the increased vimentin in LSCC might be derived from its decreased ubiquitination level and that the increased MRP1 in LSCC might be derived from its protein synthesis > degradation. GSEA and co-expression gene analyses revealed that VIM and MRP1 were involved in multiple crucial biological processes and pathways. Further, TRIM2 and NEDD4L were predicted as E3 ligases to regulate ubiquitination of vimentin and MRP1, respectively. Conclusion These findings revealed ubiquitinomic variations and molecular network alterations in LSCC, which is in combination with multiomics analysis to identify ubiquitination-related biomarkers for in-depth insight into the molecular mechanism and therapeutic targets and for prediction, diagnosis, and prognostic assessment of LSCC.
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Torres-Ayuso, Pedro, Elvira An, Katherine M. Nyswaner, Daniel A. Ritt, Suzanne I. Specht, Sudipto Das, Thorkell Andresson i in. "Abstract 2152: TNIK, a novel activator of FAK and YAP signaling, is a therapeutic target in lung squamous cell carcinoma". Cancer Research 82, nr 12_Supplement (15.06.2022): 2152. http://dx.doi.org/10.1158/1538-7445.am2022-2152.
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Abstract Lung squamous cell carcinoma (LSCC) is the second most common type of lung cancer. No precision therapies have been approved for the treatment of LSCC and the genetic drivers of LSCC are unknown in approximately 60% of the cases. As a result, treatment of LSCC is still limited to chemotherapy and/or radiotherapy. Analysis of LSCC samples from the TCGA reveals that nearly 50% of LSCC patients harbor distal amplification of the 3q chromosome that includes the resident protein kinase gene TNIK. Recent studies have pinpointed TNIK as a potential oncogenic driver in cancer cells with distal 3q amplification (Cancer Discov. 2013; 3:1044). However, the therapeutic potential of TNIK in LSCC remains unexplored. To determine if amplified TNIK is a genetic driver in LSCC, we analyzed TNIK expression in a panel of LSCC cell lines. We show that TNIK is overexpressed in LSCC cell lines in comparison with primary lung cells from healthy donors, consistent with observations in patient tumors based on analysis of TCGA data. Furthermore, we demonstrate that TNIK genetic depletion or pharmacological inhibition significantly reduces survival of LSCC cells with 3q amplification in vitro and in in vivo LSCC cell-line derived mouse xenografts. Importantly, we have generated LSCC patient-derived xenograft (PDX) mouse models to test TNIK inhibitors and have observed that inhibition of TNIK catalytic activity suppresses tumor growth in LSCC PDX mouse models. To elucidate the molecular mechanisms underpinning TNIK-driven LSCC cell viability we have used a combination of reverse-phase protein arrays, motif-driven screens for proteins with TNIK consensus phosphorylation sites, co-expression experiments, peptide mapping and mass spectrometry. Through these approaches, we have identified the tumor suppressor MERLIN as a novel TNIK substrate and determined that TNIK phosphorylates MERLIN at Ser13, Thr272 and Thr576. We also demonstrate that TNIK is required for stabilization of the YAP transcription factor, and activation of the focal adhesion kinase, FAK, two oncogenic pathways that are inhibited by MERLIN. In conclusion, we have pinpointed the protein kinase TNIK as a promising therapeutic target in LSCC that maintains survival of LSCC cells through modulation of novel a TNIK-MERLIN-YAP/FAK signaling pathway. Citation Format: Pedro Torres-Ayuso, Elvira An, Katherine M. Nyswaner, Daniel A. Ritt, Suzanne I. Specht, Sudipto Das, Thorkell Andresson, Christina M. Robinson, Simone Difilippantonio, Baktiar O. Karim, Benjamin E. Turk, Deborah K. Morrison, John Brognard. TNIK, a novel activator of FAK and YAP signaling, is a therapeutic target in lung squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2152.
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Mo, Bin-Yu, Jin-Shu Pang, Wen-Bin Dai, Ya-si Su, Wei Jiang i Su-Ning Huang. "A Comprehensive Evaluation of miR-144-3p Expression and Its Targets in Laryngeal Squamous Cell Carcinoma". Computational and Mathematical Methods in Medicine 2021 (16.07.2021): 1–11. http://dx.doi.org/10.1155/2021/6684186.
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Laryngeal squamous cell carcinoma (LSCC) is an aggressive type of head and neck squamous cell carcinoma (HNSCC) with a relatively high rate of morbidity and mortality. An altered miR-144-3p level in LSCC with a small number of patients has been previously reported. However, the clinical implication of miR-144-3p and its involved mechanism underlying this disease is not clearly elucidated. In this work, we aimed to confirm the expression of miR-144-3p with larger samples and also to identify target genes for the investigation of the underlying mechanism of miR-144-3p in LSCC. The levels of miR-144-3p were downregulated in 155 samples of LSCC tissues as compared to 26 non-LSCC samples (SMD: -0.78; 95% confidence interval (CI): -1.23, -0.32). The AUC of 0.90 in the summarized ROC curve also indicated a potential ability to differentiate LSCC from non-LSCC tissues, with a sensitivity of 0.78 and a specificity of 0.88. With respect to the molecular mechanism, we predicted the potential targets from online-based prediction, peer-reviewed publications, and RNA-seq and microarray data. In particular, the genes influenced by transfection with miR-144-3p in the LSCC FaDu cell line were collected from the microarray GSE56243. Lastly, 12 novel targets for miR-144-3p in LSCC were obtained by different algorithms. In conclusion, our study confirmed the loss or downregulation of miR-144-3p in LSCC, which might contribute to the LSCC tumorigenesis and progression via regulation of the 12 novel targets, such as IL24, ITGA6, and CEP55. In the future, further investigations are required to validate the present results.
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Rubinstein, D., A. K. Roska i P. E. Lipsky. "Liver sinusoidal lining cells express class II major histocompatibility antigens but are poor stimulators of fresh allogeneic T lymphocytes." Journal of Immunology 137, nr 6 (15.09.1986): 1803–10. http://dx.doi.org/10.4049/jimmunol.137.6.1803.
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Abstract Guinea pig liver sinusoidal lining cells (LSLC), a mixture of Kupffer cells (KC) and sinusoidal endothelial cells (EC), were examined for their capacity to function as antigen-presenting cells (APC). LSLC were extremely poor stimulators of freshly isolated allogeneic T lymphocytes even though a large number of them expressed class II major histocompatibility complex (MHC) antigens (Ia). This deficiency could not be explained by a lack of soluble factor production by LSLC, because an interleukin 1-containing macrophage (M phi) supernatant could not restore the capacity of LSLC to stimulate allogeneic T cells. Moreover, LSLC were able to promote mitogen-induced proliferation of accessory cell-depleted T lymphocytes. No evidence of suppression was apparent in experiments in which LSLC were added to cultures of T cells stimulated by allogeneic peritoneal exudate M phi (PEM). The Ia expressed by LSLC was functional because they were able to stimulate an alloreactive T cell line. When LSLC were mixed and co-cultured with either PEM syngeneic to the responding lymphocytes or Ia-negative fibroblasts, the allostimulatory ability of LSLC was greatly augmented. In contrast, the addition of mitogen-activated T cell supernatants had only a minimal effect on the capacity of LSLC to stimulate allogeneic T cells. The data suggest that LSLC lack a biologic property that is necessary for recognition of class II MHC determinants by fresh but not primed allogeneic T cells and that is not required to support T cell activation induced by nonspecific mitogenic lectins. These findings may be important in understanding the reason that antigen introduced into the portal blood appears not to initiate an immune response.
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Wang, Ying, Qingli Huang i Faping Li. "miR-140-5p targeted FGF9 and inhibited the cell growth of laryngeal squamous cell carcinoma". Biochemistry and Cell Biology 98, nr 2 (kwiecień 2020): 83–89. http://dx.doi.org/10.1139/bcb-2018-0351.
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Increasing evidence has suggested that microRNAs (miRNAs) play critical roles in the initiation and development of cancers. Here, we found that miR-140-5p was significantly downregulated in both laryngeal squamous cell carcinoma (LSCC) tissues and cell lines. Decreased expression of miR-140-5p was significantly associated with the metastasis of LSCC. Overexpression of miR-140-5p inhibited proliferation and induced apoptosis of LSCC cells. Mechanistically, the fibroblast growth factor 9 (FGF9) was identified as the target of miR-140-5p. miR-140-5p bound the 3′-untranslated region (3′-UTR) of FGF9 and suppressed the expression of FGF9 in LSCC cells. Additionally, the level of FGF9 was upregulated in LSCC tissues and negatively correlated with the expression of miR-140-5p. Restoration of FGF9 attenuated the suppressive role of miR-140-5p in regulating the growth of LSCC cells. Collectively, these results indicated that the tumor suppressive function of miR-140-5p in LSCC was partially exercised by modulating the expression of FGF9.
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Yang, Jiechao, Liang Zhou, Yanping Zhang, Juan Zheng, Jian Zhou, Zheqiang Wei i Jiaping Zou. "DIAPH1 Is Upregulated and Inhibits Cell Apoptosis through ATR/p53/Caspase-3 Signaling Pathway in Laryngeal Squamous Cell Carcinoma". Disease Markers 2019 (14.01.2019): 1–10. http://dx.doi.org/10.1155/2019/6716472.
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Cancer bioinformatics has been used to screen possible key cancer genes and pathways. Here, through bioinformatics analysis, we found that high expression of diaphanous related formin 1 (DIAPH1) was associated with poor overall survival in head and neck squamous cell carcinoma and laryngeal squamous cell carcinoma (LSCC). The effect of DIAPH1 in LSCC has not been previously investigated. Therefore, we evaluated the expression, function, and molecular mechanisms of DIAPH1 in LSCC. Immunohistochemistry and western blot analysis confirmed the significant upregulation of DIAPH1 in LSCC. We used DIAPH1 RNA interference to construct two DIAPH1-knockdown LSCC cell lines, AMC-HN-8 and FD-LSC-1, and validated the knockdown efficiency. Flow cytometry data showed that DIAPH1 inhibited apoptosis. Further, western blot analysis revealed that DIAPH1 knockdown increased the protein levels of ATR, p-p53, Bax, and cleaved caspase-3, -8, and -9. Thus, DIAPH1 is upregulated in LSCC and may act as an oncogene by inhibiting apoptosis through the ATR/p53/caspase-3 pathway in LSCC cells.