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In this study, titanium dioxide (TiO2) nanofilms with nanoparticle structure were grown in situ on metallic aluminum (Al) sheets using a simple sol-hydrothermal method. Al sheets were chosen because they can form Schottky junctions with TiO2 during the calcination process, thus achieving a tight bonding between the nanoparticles and the solid substrate, which cannot be achieved with conventional glass substrates. The substrates synthesized with different contents of titanium butoxide [Ti(OBu)4] were investigated using 4-mercaptobenzoic acid as a probe molecule, and the results showed that the substrate with 9 % of the total volume of Ti(OBu)4 had the highest surface-enhanced Raman scattering (SERS) performance. As a low-cost SERS substrate that is simple to synthesize, it has excellent signal reproducibility, with a relative standard deviation of 4.51 % for the same substrate and 6.43 % for different batches of synthesized substrates. Meanwhile, the same batch of substrate can be stored at room temperature for at least 20 weeks and still maintain stable SERS signals. In addition, the synthetic substrate was used to quantitatively detect urea with a detection limit of 4.23 × 10-3 mol/L, which is comparable to the application of noble metal substrates. The feasibility of this method was verified in human urine, and the results were consistent with the clinical results, indicating that this method has great potential for clinical application.
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Background: Bladder cancer is a common malignant tumor of the urinary system. The progression of the condition is associated with a poor prognosis, so it is necessary to identify new biomarkers to improve the diagnostic rate of bladder cancer. Methods: In this study, 338 urine samples (144 bladder cancer, 123 healthy control, 32 cystitis, and 39 upper urinary tract cancer samples) were collected, among which 238 samples (discovery group) were analyzed by LC-MS. The urinary proteome characteristics of each group were compared with those of bladder cancer, and the differential proteins were defined by bioinformatics analysis. The pathways and functional enrichments were annotated. The selected proteins with the highest AUC score were used to construct a diagnostic panel. One hundred samples (validation group) were used to test the effect of the panel by ELISA. Results: Compared with the healthy control, cystitis and upper urinary tract cancer samples, the number of differential proteins in the bladder cancer samples was 325, 158 and 473, respectively. The differentially expressed proteins were mainly related to lipid metabolism and iron metabolism and were involved in the proliferation, metabolism and necrosis of bladder cancer cells. The AUC of the panel of APOL1 and ITIH3 was 0.96 in the discovery group. ELISA detection showed an AUC of 0.92 in the validation group. Conclusion: This study showed that urinary proteins can reflect the pathophysiological changes in bladder cancer and that important molecules can be used as biomarkers for bladder cancer screening. These findings will benefit the application of the urine proteome in clinical research.
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Sensitive and multiple detection of the biomarkers of type 1 diabetes mellitus (T1DM) is vital to the early diagnosis and clinical treatment of T1DM. Herein, we developed a SERS-based biosensor using polyvinylidene fluoride (PVDF) membranes as a flexible support for the detection of glutamic acid decarboxylase antibodies (GADA) and insulin autoantibodies (IAA). Two kinds of silver-gold core-shell nanotags embedded with Raman probes and attached with GADA or IAA antibodies were synthesized to capture the targets, enabling highly sensitive and highly selective detection of GADA and IAA. The embedded Raman probes sandwiched between silver and gold layers guaranteed spectral stability and reliability. Moreover, the utilization of two Raman probes enables simultaneous and multiplexing detection of both GADA and IAA, improving the detection accuracy for T1DM. The proposed SERS-based method has been proven feasible for clinical sample detection, demonstrating its great potential in sensitive, reliable, and rapid diagnosis of T1DM.
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Técnicas Biosensibles , Diabetes Mellitus Tipo 1 , Nanopartículas del Metal , Humanos , Diabetes Mellitus Tipo 1/diagnóstico , Plata , Reproducibilidad de los Resultados , Biomarcadores , Anticuerpos , Oro , Espectrometría Raman/métodosRESUMEN
In diagnosing prostate cancer and distinguishing it from other prostate diseases, the ratio of the concentration of free prostate-specific antigen (f-PSA) to total prostate-specific antigen (t-PSA), i.e., (f-PSA%) is more accurate than the concentration of t-PSA alone. Immunoassay based on surface-enhanced Raman scattering (SERS) frequency shift has been proven to be particularly suitable for detecting large biomolecules with high reproducibility. Along similar lines, the present study developed a SERS-based biosensor that simultaneously detects t-PSA and f-PSA. The 4-mercaptobenzoic acid (MBA) on the immunocapture substrate is coupled to the t-PSA antibody through the carboxyl group, and the combination of t-PSA induces the Raman frequency shifts of MBA. The immunocolloidal gold attached with f-PSA antibodies selectively capture the f-PSA that immobilized on the MBA-modified SERS substrates, allowing for f-PSA quantification according to the SERS intensities of the 5, 5'-Dithiobis (succinimidyl-2-nitrobenzoate) (DSNB) probe. The results show that f-PSA and t-PSA have good linear response in the concentration scale of 0.1-20 ng/mL, and 1-200 ng/mL, respectively. The biosensor combines Raman frequency shifts and intensities, which greatly simplifies traditional procedures for f-PSA% detection. All the results demonstrated the great potential of the proposed biosensor in highly reproducible and accurate diagnosis of prostate cancers.
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Técnicas Biosensibles , Nanopartículas del Metal , Neoplasias de la Próstata , Masculino , Humanos , Antígeno Prostático Específico , Reproducibilidad de los Resultados , Neoplasias de la Próstata/diagnóstico , Anticuerpos , Espectrometría Raman/métodos , Oro/química , Nanopartículas del Metal/químicaRESUMEN
Iodine excess may cause and aggravate autoimmune thyroiditis (AIT), which is regarded as a typical kind of autoimmune disease mainly mediated by CD4+ T cells. Thus far, it is unclear whether T helper (Th) 9 cells, a novel subpopulation of CD4+ T cells, play a potential role in AIT. Therefore, in the present study, changes in Th9 cells were detected in murine models of AIT induced by excess iodine intake to explore the possible immune mechanism. Female C57BL/6 mice were divided into 7 groups (n = 8) and were supplied with water containing 0.005% sodium iodide for 0, 2, 4, 6, 8, 10, and 12 weeks. With the extension of the high-iodine intake duration, the incidence of thyroiditis and the spleen index were significantly increased, and serum thyroglobulin antibody (TgAb) titers and interleukin 9 (IL-9, major cytokine from Th9 cells) concentrations were also increased. Additionally, it was revealed that the percentages of Th9 cells in spleen mononuclear cells (SMCs) and thyroid tissues were both markedly elevated and accompanied by increased mRNA and protein expression of IL-9 and key transcription factors of Th9 cells (PU.1 and IRF-4). Significantly, dynamic changes in Th9 cells were found, with a peak at 8 weeks after high iodine intake, the time point when thyroiditis was the most serious. Importantly, Th9 cells were detected in the areas of infiltrating lymphocytes in thyroid sections. In conclusion, the continuously increasing proportions of Th9 cells may play an important role in the occurrence and development of AIT induced by high iodine intake.
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Yodo , Tiroiditis Autoinmune , Femenino , Animales , Ratones , Interleucina-9/efectos adversos , Yodo/efectos adversos , Ratones Endogámicos C57BL , Células Th17/metabolismoRESUMEN
BACKGROUND AND AIMS: Psychological symptoms are prevalent among individuals with non-communicable diseases, while the longitudinal association between triglyceride glucose (TyG) index, an indicator of metabolic health, and depression progression remains unclear yet. This study aims to investigate the association of baseline TyG index and depression progression in middle-aged and elder adults. METHODS AND RESULTS: This retrospective cohort study enrolled 8287 participants aged 45 years or above from national China Health and Retirement Longitudinal Study in visit 1 (2011-2012), which were biennially followed for depression score until visit 4 (2017-2018). Multivariate-adjusted regression models were used to evaluate the association of baseline TyG index with the individual level change rate and slope of depression score. The mean age (±SD) of participants was 58.25 ± 9.10 years, and 3806 (45.9%) were men. There was no significant difference of depression score at baseline across TyG quartile groups (P = 0.228). Participants in the highest quartile of TyG index had a 0.124 (95% CI: 0.018-0.230) higher change rate of depression score, and a 0.127 (95% CI: 0.019-0.235) higher change slope, compared to those in the lowest. The observed associations were consistent in multiple sensitivity analyses, and stable in men, the elder, and overweight people. CONCLUSION: TyG index is positively associated with depression progression especially in men, the elder and overweight people, which provides new insights for the primary prevention of depression disorder.
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Glucemia , Glucosa , Masculino , Persona de Mediana Edad , Humanos , Adulto , Anciano , Femenino , Triglicéridos , Glucemia/metabolismo , Factores de Riesgo , Estudios Longitudinales , Estudios Retrospectivos , Depresión/diagnóstico , Depresión/epidemiología , Sobrepeso , BiomarcadoresRESUMEN
Understanding the structure-activity correlation and reaction mechanism of the catalytic process in an acetic acid-sodium acetate (HAc-NaAc) buffer environment is crucial for the design of efficient nanozymes. Here, we first reported a lattice restructuration of Au-LaNiO3-δ nanofibers (NFs) after acidification with the HAc-NaAc buffer to show a significantly enhanced oxidase-like property. Surface-enhanced Raman spectroscopy (SERS) and density functional theory (DFT) calculation confirm the direct evidence for the formation of specific enhanced intermediate O-O species after acidification, indicating that the insertion of the carboxyl group in the A-Au/LaNiO3-δ NFs plays crucial roles in both producing vacancies in HAc-NaAc solution from its dissociation during the catalytic process and the protection of the vacancies, which can be directly interacted with oxygen in the environment to produce O-O species, realizing the enhanced oxidation of substrate molecules. The insertion of the carboxyl group increased the oxidase-like catalytic activity by 2.38 times and the SERS activity by 5.27 times. This strategy offers a way to construct an efficient nanozyme-linked immunosorbent assay system for the diagnosis of cancer through the highly sensitive SERS identification of exosomes.
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Nanopartículas del Metal , Nanopartículas del Metal/química , Oro/química , Espectrometría Raman/métodos , Oxidorreductasas , AcetatosRESUMEN
Background: 5-Fluorouracil (5-FU) is one of the most common chemotherapy drugs used to treat colorectal cancer (CRC), which often develops resistance in more than 15% of patients. Curcumin, an active component of Curcuma longa, has been reported to show antitumor activity in CRC and, furthermore, enhance the effect of chemotherapy against colorectal cancer cells. However, the molecular mechanisms underlying the sensitizing effect of curcumin on 5-FU have not been largely elucidated. In this study, we aimed to systematically investigate the role of curcumin as a chemosensitizer for the treatment of CRC, along with the key events responsible for its pharmaceutical effect, which may lead to better clinical outcomes. Methods: A high-resolution 2DE-based proteomics approach was used to characterize global protein expression patterns in CRC cells treated with 5-FU both in combination with curcumin or without. The differentially expressed proteins were obtained from the 2DE analysis and subsequently identified by MALDI-TOF MS or nano-ESI-MS/MS, some of which were validated by the Western blot. Intracellular reactive oxygen species (ROS) were measured to assess the change in the redox environment resulting from the drug treatment. Results: A series of proteins with altered abundances were detected and identified by MALDI-TOF or nano-MS/MS. From a total of 512 isolated proteins, 22 proteins were found to be upregulated and 6 proteins were downregulated. Intracellular ROS was significantly elevated after curcumin treatment. Furthermore, mass spectrometry data revealed that some of the proteins appeared to have more oxidized forms upon curcumin treatment, suggesting a direct role for ROS in the chemosensitizing effect of curcumin. Conclusion: The effect of curcumin in enhancing chemosensitivity to 5-FU is a complex phenomenon made up of several mechanisms, including enhancement of the intracellular level of ROS. Our findings presented here could provide clues for a further study aimed at elucidating the mechanisms underlying the chemosensitizing effect of curcumin.
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The effects of different emulsifiers, such as soy protein isolate-sucrose ester (SPI-SE) and whey protein isolate-sucrose ester (WPI-SE), on the properties of the emulsion during the microencapsulation of cannabis oil were studied. The influence of SE concentration on the emulsion properties of the two emulsifying systems was analyzed. The results of the adsorption kinetics show that SE can decrease the interfacial tension, particle size and zeta potential of the emulsions. The results of the interfacial protein concentration show that SE could competitively replace the protein at the oil-water interface and change the strength of the interfacial film. The results of the viscoelastic properties show that the emulsion structure of the two emulsion systems results in the maximum value when the concentration of SE is 0.75% (w/v), and the elastic modulus (G') of the emulsion prepared with SPI-SE is high. The viscosity results show that all emulsions show shear-thinning behavior and the curve fits well with the Ostwald-Dewaele model. The addition of SE in the emulsions of the two emulsion systems can effectively stabilize the emulsion and change the composition and strength of the oil-water interface of the emulsion. The cannabis oil microcapsules prepared with protein-SE as an emulsion system exhibit high quality.
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Previous studies reported that sex and age could influence urine metabolomics, which should be considered in biomarker discovery. As a consequence, for the baseline of urine metabolomics characteristics, it becomes critical to avoid confounding effects in clinical cohort studies. In this study, we provided a comprehensive lifespan characterization of urine metabolomics in a cohort of 348 healthy children and 315 adults, aged 1 to 78 years, using liquid chromatography coupled with high resolution mass spectrometry. Our results suggest that sex-dependent urine metabolites are much greater in adults than in children. The pantothenate and CoA biosynthesis and alanine metabolism pathways were enriched in early life. Androgen and estrogen metabolism showed high activity during adolescence and youth stages. Pyrimidine metabolism was enriched in the geriatric stage. Based on the above analysis, metabolomic characteristics of each age stage were provided. This work could help us understand the baseline of urine metabolism characteristics and contribute to further studies of clinical disease biomarker discovery.
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Líquidos Corporales , Espectrometría de Masas en Tándem , Humanos , Adulto , Niño , Anciano , Adolescente , Cromatografía Liquida/métodos , Metabolómica/métodos , Líquidos Corporales/metabolismo , Biomarcadores/metabolismoRESUMEN
BACKGROUND AND AIMS: Visceral adiposity index (VAI), an indicator of visceral fat, is associated with metabolic health and arterial stiffness. However, studies correlating VAI and stroke are limited. This study aimed to explore the association between VAI and incident stroke in the Chinese population. METHODS AND RESULTS: We retrospectively analysed the data of 9127 individuals enrolled in the China Health and Retirement Longitudinal Study. The first survey of the study was conducted during 2011-2012 and the individuals were followed up until Survey 4 (2017-2018). Multivariable-adjusted Cox regression models were used to evaluate the association between VAI and stroke. The mean age of the study population was 59.3 ± 9.5 years and 4938 (54.1%) participants were women. During the median follow-up of 5.2 [1.0-7.0] years, 833 (9.1%) participants developed stroke, and the cumulative incidence of stroke increased with increasing quartiles of VAI (8.6%, 8.7%, 9.2%, and 10.0%). Compared to those in the first quartile of VAI, individuals in the fourth quartile had an increased risk of stroke (adjusted hazard ratio, 1.45; 95% CI, 1.15-1.75). The results were stable in several sensitivity analyses. CONCLUSION: Our findings suggest a positive association between VAI and incident stroke in the Chinese population.
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Adiposidad , Accidente Cerebrovascular , Anciano , Índice de Masa Corporal , China/epidemiología , Femenino , Humanos , Grasa Intraabdominal , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Obesidad Abdominal/diagnóstico , Obesidad Abdominal/epidemiología , Jubilación , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiologíaRESUMEN
To obtain the difference of the fungal and bacterial community diversity between wild Cordyceps sinensis, artificial C. sinensis and their habitat soil, Illmina Hiseq high-throughput sequencing technology was applied. The results show that Proteobacteria was the dominant bacterial phylum in C. sinensis, Actinobacteria was the dominant bacterial phylum in soil microhabitat, Ophiocordyceps sinensis was the predominant dominant fungus of C. sinensis. The α diversity analysis showed that the fungal diversity of stroma was lower than other parts, and the fungal diversity of wild C. sinensis was lower than that of artificial C. sinensis. The ß diversity analysis showed that the fungal and bacterial community diversity of soil microhabitat samples was significantly different from that of C. sinensis. The fungal community diversity was less different between wild and artificial C. sinensis, especially in sclerotia. LEfSe analysis showed a lot of species diversity between wild and artificial C. sinensis. Those different species between wild C. sinensis, artificial C. sinensis and their habitat soil provide ideas for further research on breed and components of C. sinensis.
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Cordyceps , Microbiota , Cordyceps/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Microbiota/genética , Suelo , Microbiología del SueloRESUMEN
BACKGROUND AND AIMS: We aimed to evaluate the association between BMI change and stroke in middle-aged and older adults with type 2 diabetes and identify sex differences. METHODS AND RESULTS: The China Health and Retirement Longitudinal Study is an ongoing national population-based cohort study. Participants aged 45 or above with type 2 diabetes were enrolled and followed for stroke incidence. BMI change was defined as BMI at 2013-BMI at 2011. Of 1774 participants (mean [SD] age in 2011, 60.23 [8.88] years), 795 (44.8 %) were men. A total of 112 incident stroke cases were confirmed up to 2018. The incidence rate of stroke was similar between men and women (6.79 % vs 5.92 %, P = 0.516). BMI increase was independently associated with an increased stroke risk (adjusted odds ratio, 1.15; 95 % CI, 1.05-1.31) in men, while this positive association was not significant in women (adjusted odds ratio, 1.12; 95 % CI, 0.98-1.29). In addition, the positive dose-response relationship between BMI increase and stroke was observed only in men. CONCLUSION: Among middle-aged and older adults with type 2 diabetes, there is a sex-specific association of BMI change with stroke. An increase in BMI could result in a higher risk of incident stroke in men.
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Índice de Masa Corporal , Diabetes Mellitus Tipo 2/epidemiología , Obesidad/epidemiología , Accidente Cerebrovascular/epidemiología , Aumento de Peso , Factores de Edad , Anciano , China/epidemiología , Diabetes Mellitus Tipo 2/diagnóstico , Femenino , Humanos , Incidencia , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Obesidad/diagnóstico , Pronóstico , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Accidente Cerebrovascular/diagnóstico , Factores de TiempoRESUMEN
Glaucoma is the leading cause of irreversible blindness worldwide. The proteome characterization of glaucoma is not clearly understood. A total of 175 subjects, including 57 primary acute angle-closure glaucoma (PAACG), 50 primary chronic angle-closure glaucoma (PCACG), 35 neovascular glaucoma (NVG), and 33 cataract patients, were enrolled and comparison proteomic analysis was provided. The samples were randomly divided into discovery group or validation group, whose aqueous humor proteome was analyzed by data-independent acquisition or by parallel reaction monitoring. The common proteome features of three types of glaucoma were immune response, lipid metabolism, and cell death. Three proteins, VTN, SERPIND1, and CD14, showed significant upregulation in glaucoma and could discriminate glaucoma from cataract. Mutual differential proteomic analysis of PAACG, PCACG, and NVG showed different proteome characterization of the three types of glaucoma. NVG was characterized with activated angiogenesis. PAACG was characterized with activation of inflammation response. SERPIND1 was discovered to play vital role in glaucoma occurrences, which is associated with eye transparency decrease and glucose metabolism. This study would provide insights in understanding proteome characterization of glaucoma and benefit the clinical application of AH proteome.
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Humor Acuoso/metabolismo , Glaucoma/metabolismo , Proteoma/metabolismo , Anciano , Anciano de 80 o más Años , Catarata/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The aim of this study was to establish a method for geographical origins identification of Panax notoginseng (P. notoginseng) based on abundant chromatographic spectral information. Characteristic fingerprints of P. notoginseng extracts samples were generated by Multi-wavelength Fusion Profiling (MWFP) method based on the HPLC fingerprints established at three wavelengths of 203 nm, 270 nm and 325 nm. The samples grouping results calculated with the averagely linear quantified fingerprint method (ALQFM) and the unsupervised statistical methods based on fusion fingerprints matches with the geographical origins. The Multi-wavelength Fusion Profiling (MWFP) method has been successfully applied to identification of geographical origins of P. notoginseng and shows the advantages compared with single-channel fingerprints. In addition, eight physiologically active components, including four saponins, two flavones and two amino acids, were identified from the most relevant ingredients of P. notoginseng geographical origins by fusion fingerprint-efficacy relationship analysis. Besides the recognized active saponins, other categories of active ingredients such as flavonoids and amino acids should be paid attention to in the producing areas identification or the quality judgment of P. notoginseng.
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Aminoácidos/aislamiento & purificación , Flavonoides/aislamiento & purificación , Panax notoginseng/química , Saponinas/aislamiento & purificación , Aminoácidos/química , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Flavonoides/química , Geografía , Humanos , Panax notoginseng/clasificación , Raíces de Plantas/química , Control de Calidad , Saponinas/químicaRESUMEN
4-Cyanophenylhydrazine (4-CPH) is an organic synthesis intermediate. To date, several products derived from 4-CPH have been well studied; however, 4-CPH itself has not been extensively investigated. Herein, we performed vibrational and theoretical analyses of 4-CPH. Density functional theory (DFT) calculations were applied to predict the IR and Raman spectra of 4-CPH, which were compared with the experimental spectra. The calculated and experimental spectral results were in good agreement, except for an abnormal transformation of the protonated 4-CPH cyano group (C≡N), which was observed in the theoretical IR spectrum. Several wavefunction analyses revealed that this transformation was due to the protonation-induced depolarization of the molecule. Moreover, we verified the applicability of 4-CPH as a probe for surface-enhanced Raman spectroscopy (SERS). We observed a pH-dependent shift in the cyano bond frequency within the silent region and determined, as a novel discovery, that this shift was induced by 4-CPH protonation. Our results provide considerable, fundamental information that confirms the potential of 4-CPH as a SERS probe.
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Aqueous humor (AH) proteins are involved in many physiological and pathological processes of the eye. The proteome analysis of AH is important to understand its physiological and pathophysiological functions. In the present study, AH samples obtained from 21 cataract volunteers were pooled together. After high-pH RPLC offline separation, the pooled sample was analyzed by LC-MS/MS to provide a comprehensive profile of AH proteome. The function analysis was provided by the GO and IPA annotation. In order to determine whether the AH proteome can reflect the pathophysiological changes of the disease, DIA technology was used to analyze the AH samples obtained from three neovascular glaucoma (NVG) patients (six samples) before and after drug treatment. The differential proteins were validated by PRM technology in an independent group (14 samples). In the AH proteome database, 802 proteins were identified, and 318 proteins were identified for the first time. Furthermore, 480 proteins were quantified based on the peak intensity-based semiquantification (iBAQ), which ranged by approximately 7 orders of magnitude. These proteins are primarily involved in immunity- and inflammation-related pathways. The differential AH proteomic analysis in NVG treatment revealed that the AH proteome can reflect the pathophysiological changes of drug treatment. Angiogenesis and thrombus coagulation progression are deeply involved in NVG treatment. The present experiment provided a comprehensive AH proteome analysis and expanded the profile of human AH proteome. The differential AH proteomic analysis of NVG treatment indicated that AH proteome can reflect the pathophysiological changes in drug intervention.
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BACKGROUND: To investigate the biological relationship, mechanism between perilipin2 and the occurrence, advancement of gastric carcinoma, and explore the mechanism of lipid metabolism disorder leading to gastric neoplasm, and propose that perilipin2 is presumably considered as a potential molecular biomarker of gastric carcinoma. METHODS: RNA-seq was applied to analyze perilipin2 and differentially expressed genes modulated by perilipin2 in neoplastic tissues of both perilipin2 overexpression and knockdown groups in vivo. The mechanism was discovered and confirmed by Rt-qPCR, immunoblotting, immunohistochemistry, staining and microassay, respectively. Cellular function experiments were performed by flow cytometry, CCK8, clonogenic assay, etc. RESULTS: Overexpression and knockdown of perilipin2 augmented the proliferation and apoptosis of gastric carcinoma cell lines SGC7901 and MGC803, respectively. The neoplastic cells with perilipin2-overexpression obtained more conspicuously rapid growth than knockdown group in vivo, and perilipin2 affected the proliferation and apoptosis of gastric carcinoma cells by modulating the related genes:acyl-coa synthetase long-chain family member 3, arachidonate 15-lipoxygenase, microtubule associated protein 1 light chain 3 alpha, pr/set domain 11 and importin 7 that were participated in Ferroptosis pathway. Moreover, RNA-seq indicated perilipin2 was an indispensable gene and protein in the suppression of Ferroptosis caused by abnormal lipometabolism in gastric carcinoma. CONCLUSION: Our study expounded the facilitation of perilipin2 in regulating the proliferation and apoptosis of gastric carcinoma cells by modification in Ferroptosis pathway, and we interpreted that the mechanism of gastric neoplasm caused by obesity, we also discovered that pr/set domain 11 and importin 7 are novel transcription factors relevant to gastric carcinoma. Furthermore, perilipin2 probably serves not only as a diagnostic biomarker, but also a new therapeutic target.
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Biomarcadores de Tumor/genética , Ferroptosis/genética , Metabolismo de los Lípidos/genética , Perilipina-2/metabolismo , Neoplasias Gástricas/patología , Animales , Apoptosis , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Perilipina-2/antagonistas & inhibidores , Perilipina-2/genética , RNA-Seq , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
An increasing number of studies have shown that kinesin family member 20A (KIF20A) was overexpressed in several types of cancer, and its overexpression correlated with the oncogenesis and prognosis of cancers. However, little is known about the roles of KIF20A in human non-small cell lung cancer (NSCLC). Thus, the aim of the present study was to demonstrate the expression of KIF20A in human NSCLC and reveal its biological functions and the underlying mechanisms. qRT-PCR, western blot and immunohistochemistry were used to assess the expression of NSCLC patient specimens and NSCLC cell lines. The functions of KIF20A in migration and invasion were determined using Transwell assay. Cell proliferation capacity was performed by CKK-8 assay. We demonstrated that KIF20A was overexpressed in NSCLC specimens compared with the adjacent non-tumorous specimens, and high expression of KIF20A was associated with clinical stage and metastasis in NSCLC. Decreased expression of KIF20A inhibited NSCLC cells migration, invasion and proliferation. Most importantly, further experiments demonstrated that decreased the expression of KLF20A significantly downregulated expression of p-JNK and MMP7, which indicated that knockdown of KIF20A alters lung cancer cell phenotype and regulates JNK pathways. These results suggest that KIF20A may act as a putative oncogene and a potential therapeutic target in NSCLC.
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Background: The association of pathological states with N-glycosylation of haptoglobin-ß has attracted increasing attention. Materials & Methods: In the present study, disease-specific haptoglobin-ß (DSHp-ß) was separated from serum immunoinflammation-related protein complexes (IIRPCs) of 600 participants including 300 patients with benign lung diseases (BLDs) and 300 patients with non-small cell lung cancer (NSCLC). The enriched glycopeptides of the tryptic digests of the DSHp-ß were analyzed using matrix assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS). Results: 20 of glycopeptides were detected for each sample. The statistical analysis has indicated that significant changes in the sialylation of DSHp-ß between BLDs and NSCLC patients were observed. The age- and sex-matched participants were randomly clarified into the training set and the validation set. Receiver operating characteristic (ROC) analysis has revealed that the level ratio of glycopeptides (G2G3/G2G3S4) at the sites of Asn207/211 has potential capability to distinguish BLDs from NSCLC, with the sensitivity of 74.4%, the specificity of 82.8%, and the area under curve (AUC) of 0.805. Conclusion: The glycosylation of DSHp-ß can distinguish NSCLC from BLDs with high diagnostic accuracy compared with current clinical available serum markers.