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BACKGROUND: Gastric intestinal metaplasia (IM) is a precancerous lesion that is associated with an elevated risk of gastric carcinogenesis. Weiwei Decoction (WWD) is a promising traditional Chinese herbal formula widely employed in clinical for treating IM. Previous studies suggested the potential involvement of the olfactomedin 4 (OLFM4)/nucleotide-binding oligomerization domain 1 (NOD1)/caudal-type homeobox gene 2 (CDX2) signaling pathway in IM regulation. AIM: To verify the regulation of the OLFM4/NOD1/CDX2 pathway in IM, specifically investigating WWD's effectiveness on IM through this pathway. METHODS: Immunohistochemistry for OLFM4, NOD1, and CDX2 was conducted on tissue microarray. GES-1 cells treated with chenodeoxycholic acid were utilized as IM cell models. OLFM4 short hairpin RNA (shRNA), NOD1 shRNA, and OLFM4 pcDNA were transfected to clarify the pathway regulatory relationships. Protein interactions were validated by co-immunoprecipitation. To explore WWD's pharmacological actions, IM rat models were induced using N-methyl-N'-nitro-N-nitrosoguanidine followed by WWD gavage. Gastric cells were treated with WWD-medicated serum. Cytokines and chemokines content were assessed by enzyme-linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction. RESULTS: The OLFM4/NOD1/CDX2 axis was a characteristic of IM. OLFM4 exhibited direct binding and subsequent down-regulation of NOD1, thereby sustaining the activation of CDX2 and promoting the progression of IM. WWD improved gastric mucosal histological lesions while suppressing intestinal markers KLF transcription factor 4, villin 1, and MUCIN 2 expression in IM rats. Regarding pharmacological actions, WWD suppressed OLFM4 and restored NOD1 expression, consequently reducing CDX2 at the mRNA and protein levels in IM rats. Parallel regulatory mechanisms were observed at the protein level in IM cells treated with WWD-medicated serum. Furthermore, WWD-medicated serum treatment strengthened OLFM4 and NOD1 interaction. In case of anti-inflammatory, WWD restrained interleukin (IL)-6, interferon-gamma, IL-17, macrophage chemoattractant protein-1, macrophage inflammatory protein 1 alpha content in IM rat serum. WWD-medicated serum inhibited tumor necrosis factor alpha, IL-6, IL-8 transcriptions in IM cells. CONCLUSION: The OLFM4/NOD1/CDX2 pathway is involved in the regulation of IM. WWD exerts its therapeutic efficacy on IM through the pathway, additionally attenuating the inflammatory response.
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To clarify the relationship between gelatinization degree and structure characteristics, oat kernels were roasted to different gelatinization degree of 15 %-90 % based on tempering water content of 22.5 %-35 %, and the structure characteristics of starch and protein were evaluated. The results showed that the increased gelatinization degree dependent on tempering water content promoted protein aggregation on the surface of starch particles, forming larger aggregates with molecular weight >100 kDa. Oat kernels presented a dense starch gel network structure induced by gelatinized starch. Partial gelatinization of starch led to a decrease in pasting viscosities (setback viscosity, 3.91 Pa·s-1.59 Pa·s) and enthalpy (5.12 J/g-0.11 J/g). With the increase of gelatinization degree, the starch crystal structure conversed from A + V type to V type, accompanied by the formation of starch-lipid complexes and a decrease of relative crystallinity (22.28 %-8.72 %). Moreover, 50 % gelatinized oat flour possessed the highest ß-sheet structure (38.04 %), but a decrease in surface hydrophobicity and an increase in endogenous fluorescence intensity were found in oat flour of gelatinization degree >50 %. This study provided a theoretical reference for the application of oat flour with different gelatinization degrees to match suitable products.
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Avena , Amido , Amido/química , Farinha , Viscosidade , Água/químicaRESUMO
Gastric cancer (GC) is the fifth most common cause of cancer-associated deaths; however, its treatment options are limited. Despite clinical improvements, chemotherapy resistance and metastasis are major challenges in improving the prognosis and quality of life of patients with GC. Therefore, effective prognostic biomarkers and targets associated with immunological interventions need to be identified. Solute carrier family 2 member 2 (SLC2A2) may serve a role in tumor development and invasion. The present study aimed to evaluate SLC2A2 as a prospective prognostic marker and chemotherapeutic target for GC. SLC2A2 expression in several types of cancer and GC was analyzed using online databases, and the effects of SLC2A2 expression on survival prognosis in GC were investigated. Clinicopathological parameters were examined to explore the association between SLC2A2 expression and overall survival (OS). Associations between SLC2A2 expression and immune infiltration, immune checkpoints and IC50 were estimated using quantification of the tumor immune contexture from human RNA-seq data, the Tumor Immune Estimation Resource 2.0 database and the Genomics of Drug Sensitivity in Cancer database. Differential SLC2A2 expression and the predictive value were validated using the Human Protein Atlas, Gene Expression Omnibus, immunohistochemistry and reverse transcription-quantitative PCR. SLC2A2 expression was downregulated in most types of tumor but upregulated in GC. Functional enrichment analysis revealed an association between SLC2A2 expression and lipid metabolism and the tumor immune microenvironment. According to Gene Ontology term functional enrichment analysis, SLC2A2-related differentially expressed genes were enriched predominantly in 'chylomicron assembly', 'plasma lipoprotein particle assembly', 'high-density lipoprotein particle', 'chylomicron', 'triglyceride-rich plasma lipoprotein particle', 'very-low-density lipoprotein particle'. 'intermembrane lipid transfer activity', 'lipoprotein particle receptor binding', 'cholesterol transporter activity' and 'intermembrane cholesterol transfer activity'. In addition, 'cholesterol metabolism', and 'fat digestion and absorption' were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes pathway analysis. Patients with GC with high SLC2A2 expression had higher levels of neutrophil and M2 macrophage infiltration and a significant inverse correlation was observed between SLC2A2 expression and MYC targets, tumor mutation burden, microsatellite instability and immune checkpoints. Furthermore, patients with high SLC2A2 expression had worse prognosis, including OS, disease-specific survival and progression-free interval. Multivariate regression analysis demonstrated that SLC2A2 could independently prognosticate GC and the nomogram model showed favorable performance for survival prediction. SLC2A2 may be a prospective prognostic marker for GC. The prediction model may improve the prognosis of patients with GC in clinical practice, and SLC2A2 may serve as a novel therapeutic target to provide immunotherapy plans for GC.
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The present study aims to investigate the genotype distribution of Human papillomavirus (HPV) and variations of HPV18 and HPV58 infection among 6538 females in Luoyang city during 2019-2021. The overall positive rate of females with HPV infection was 12.34%, with 9.74% were infected with single HPV and 2.60% with multiple HPVs. The prevalent rate of high-risk HPV (HR-HPV) was 9.85% and the top five HR-HPV genotypes were HPV52 (1.94%), HPV16 (1.93%), HPV58 (1.48%), HPV51 (1.02%) and HPVV39 (0.99%). Two peaks of HPV infections rates were observed in females aged ≤ 20 and 61-65 years old. To characterize mutations, 39 HPV18 and 56 HPV58 L1, E6 and E7 genes were sequenced and submitted to GenBank. In the HPV18 E6-E7-L1 sequences, 38 nucleotides changes were observed with 10/38 were non-synonymous mutations (5 in E6 gene, 1 in E7 gene and 4 in L1 gene). In the HPV58 E6-E7-L1 sequences, 53 nucleotides changes were observed with 23/53 were non-synonymous mutations (3 in E6 gene, 5 in E7 gene and 15 in L1 gene). Phylogenetic analysis based on L1 gene showed that 92.3% (36/39) of HPV18 isolates fell into sublineage A1 and 7.7% (3/39) belonged to A5. For HPV58, 75.0% (42/56) isolates belonged to sublineage A1 and 25.0% (14/56) were sublineage A2. There was no association between amino mutation and cervical lesions. The present study provides basic information about the distribution, genotypes and variations of HPV among females population in Luoyang city, which would assist in the formulation of HPV screening and vaccination programs and preventive strategies for HPV-attributable cancer in this region.
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Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/genética , Papillomavirus Humano 18/genética , Proteínas Oncogênicas Virais/genética , Papillomavirus Humano , Filogenia , Neoplasias do Colo do Útero/epidemiologia , Papillomaviridae/genética , Mutação , Genótipo , Nucleotídeos , China/epidemiologiaRESUMO
Liquid biopsy has been taken as a minimally invasive examination and a promising surrogate to the clinically applied tissue-based test for the diagnosis and molecular analysis of cancer. Extracellular vesicles (EVs) carry complex molecular information from the tumor, allowing for the multicomponent analysis of cancer and would be beneficial to personalized medicine. In this review, the advanced nanomaterials and nanotechniques for the detection and molecular profiling of EVs, highlight the advantages of nanotechnology in the high-purity isolation and the high-sensitive and high-specific identification of EVs, are summarized. An outlook on the clinical application of nanotechnology-based liquid biopsy in the diagnosis, prognostication, and surveillance of cancer is also provided. It provides information for developing liquid biopsy based on EVs by discussing the advantages and challenges of functionalized nanomaterials and various nanotechnologies.
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Vesículas Extracelulares , Nanoestruturas , Neoplasias , Humanos , Biomarcadores Tumorais , Vesículas Extracelulares/patologia , Nanotecnologia , Neoplasias/diagnósticoRESUMO
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases characterized by progressive cognitive decline. Early diagnosis and dynamic monitoring are essential to the treatment and care of AD but challenging. Here we develop a noninvasive, blood-based AD detection method based on surface plasmonic resonance imaging (SPRi) technique. The functionalized sensing SPRi chips were constructed with self-assembled loop-displaying peptoid nanosheets to improve the detection sensitivity of plasma amyloid ß42 (Aß42). We analyze the plasma from 30 clinically diagnosed AD patients, 29 amnestic cognitive impairment (aMCI) patients, and 30 control individuals and demonstrate that this sensing system can significantly distinguish the three groups with high sensitivity and specificity. In the follow-up studies of the aMCI patients, we find that decrease in the binding signals in the patients correlates with the disease progression into AD whereas the almost unchanged signals correlate with stable disease remaining at aMCI status. These results show the capability of the peptoid-nanosheet-based SRPi sensing system for the early diagnosis and dynamic monitoring of AD.
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Doença de Alzheimer , Disfunção Cognitiva , Peptoides , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico , Progressão da Doença , Humanos , Testes NeuropsicológicosRESUMO
When studying the altered expression of genes associated with cartilage regeneration by quantitative real-time RT-PCR (RT-qPCR), reference genes with highly stable expression during different stages of chondrocyte developmental are necessary to normalize gene expression accurately. Until now, no reports evaluating expression changes of commonly used reference genes in rabbit articular cartilage have been published. In this study, defects were made in rabbit articular cartilage, with or without insulin-like growth factor 1 (IGF-1) treatment, to create different chondrocyte living environments. The stability and intensity of the expressions of the candidate reference genes glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 18S Ribosomal RNA (18S rRNA), cyclophilin (CYP), hypoxanthine phosphoribosyl transferase (HPRT1), and beta-2-microglobulin (B2M) were evaluated. The data were analyzed by geNorm and NormFinder. B2M and 18S rRNA were identified to be suitable reference genes for rabbit cartilage tissues.
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Cartilagem/metabolismo , Perfilação da Expressão Gênica , Cicatrização/genética , Ferimentos e Lesões/genética , Animais , Modelos Animais , Coelhos , Reação em Cadeia da Polimerase em Tempo RealRESUMO
A field experiment was conducted to study the effects of different mulching measures on the diurnal and seasonal variations of winter wheat field soil respiration in dry land region of Loess Plateau. Four treatments were installed, i. e., 300 kg x hm(-2) straw mulching (M300), 600 kg x hm(-2) straw mulching (M600), plastic film mulching (PM), and no mulching (CK). In all treatments, the soil respiration rate had a decreasing trend from autumn to winter, but increased rapidly after winter and peaked at jointing stage. Comparing with CK, treatments mulching promoted the soil respiration obviously from wintering to maturing stage, with significant differences between treatment PM and the others. The average soil respiration rate in treatments M300, and M600 in whole growth period was 1. 52 micromol CO2 x m(-2) x s(-1) and 1. 47 micromol CO2 x m(-2) x s(-1), being 10. 2% and 6.6% higher than the CK (1.38 micromol CO2 x m(-2) s(-1)) , respectively, and that in treatment PM was 3. 63 micromol CO2 x m(-2) x s(-1), 163% higher than CK. The diurnal variation of soil respiration rate in CK and in M300 and M600 presented a single peak curve and peaked at 12:00 and 14:00, respectively, but for PM treatment, the diurnal variation of soil respiration rate was similar with that in CK at jointing stage while presented a bimodal curve at maturing stage, with the peaks at 12:00 and 16:00, respectively. Soil respiration rate had an exponential correlation with soil temperature, and a parabolic correlation with soil moisture.