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1.
BMC Pregnancy Childbirth ; 24(1): 530, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39134987

RESUMEN

BACKGROUND: Despite extensive research, the identification of effective biomarkers for early prediction of preterm birth (PTB) continues to be a challenging endeavor. This study aims to identify amniotic fluid (AF) protein biomarkers useful for the early diagnosis of PTB. METHODS: We initially identified the protein expression profiles in the AF of women with PTB (n = 22) and full-term birth (FTB, n = 22), from the First People's Hospital of Yunnan Province who underwent amniocentesis from November 2019 to February 2020, using mass spectrometry employing the data-independent acquisition (DIA) technique, and then analyzed differentially expressed proteins (DEPs). Subsequently, the least absolute shrinkage and selection operator (LASSO) and random forest analysis were employed to further screen the key proteins for PTB biomarker identification. The receiver operating characteristic (ROC) analysis, calibration plots, and decision curve analyses (DCA) were utilized to assess the discrimination and calibration of the key biomarkers. RESULTS: A total of 25 DEPs were identified between the PTB and FTB groups, comprising 13 up-regulated and 12 down-regulated proteins. Three key protein biomarkers for early PTB diagnosis were identified: IL1RL1 (interleukin-1 receptor-like 1), APOE (apolipoprotein E), and NECTIN4 (nectin cell adhesion molecule 4). The results of the ROC analysis showed that the area under the curve (AUC) of the three proteins combined as a biomarker for early diagnosis of PTB was 0.913 (95% CI: 0.823-1.000), with a sensitivity of 0.864 and a specificity of 0.955, both superior to those of the individual biomarkers. Bootstrap internal validation revealed a concordance index (C-index) of 0.878, with a sensitivity of 0.812 and a specificity of 0.773, indicating the robust predictive performance of these biomarkers. CONCLUSIONS: We identified three previously unexplored yet potentially useful protein biomarkers in AF for early PTB diagnosis: IL1RL1, APOE, and NECTIN4.


Asunto(s)
Líquido Amniótico , Apolipoproteínas E , Biomarcadores , Nacimiento Prematuro , Proteómica , Humanos , Femenino , Nacimiento Prematuro/diagnóstico , Nacimiento Prematuro/metabolismo , Embarazo , Adulto , Biomarcadores/metabolismo , Biomarcadores/análisis , Proteómica/métodos , Líquido Amniótico/metabolismo , Líquido Amniótico/química , Moléculas de Adhesión Celular/análisis , Moléculas de Adhesión Celular/metabolismo , Nectinas/metabolismo , Curva ROC , Amniocentesis
2.
Am J Sports Med ; 52(7): 1719-1727, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38702960

RESUMEN

BACKGROUND: The incremental biological changes in the synovial microenvironment of the shoulder in acute and chronic instability that may contribute to joint degeneration are poorly understood. Proteomic analysis of synovial fluid in patients with shoulder instability may improve our understanding of proteins that are shed into shoulder synovial fluid after an injury. HYPOTHESIS: Injury-specific factors such as the direction of instability and the severity of glenoid and humeral bone loss are associated with the proteome of synovial fluid in patients with shoulder instability. STUDY DESIGN: Descriptive laboratory study. METHODS: Synovial fluid lavage samples were compared between patients with anterior (n = 12) and posterior (n = 8) instability and those without instability (n = 5). Synovial proteins were identified with liquid chromatography-tandem mass spectrometry. Orthogonal validation of protein targets found to be significant on tandem mass spectrometry was performed in a separate set of prospective patients with Western blotting. Data were processed and analyzed, and P values were adjusted with the Benjamini-Hochberg method for multiple comparisons. RESULTS: A total of 25 patients were included. Tandem mass spectrometry identified 720 protein groups in synovial fluid of patients with shoulder instability. There were 4 synovial proteins that were significantly expressed in patients with anterior instability relative to posterior instability: periostin (POSTN) (adjusted P value = .03; log fold change [logFc] = 4.7), transforming growth factor beta-induced protein ig-h3 (adjusted P value = .05; logFc = 1.7), collagen type VI alpha-3 chain (adjusted P value = .04; logFc = 2.6), and coagulation factor V (adjusted P value = .04; logFc = -3.3). Among these targets, POSTN showed a moderate correlation with the Hill-Sachs lesion size (r = 0.7). Prospective validation with Western blotting confirmed a significantly higher level of POSTN in synovial fluid of patients with anterior instability (P = .00025; logFc = 5.1). CONCLUSION: Proteomic analysis enriched our understanding of proteins that were secreted into shoulder synovial fluid of patients with shoulder instability. The identification of POSTN, a proinflammatory catabolic protein involved with tissue remodeling and repair, as a significant target in anterior shoulder instability is a novel finding. Therefore, further study is warranted to determine the role that POSTN may play in the progression of bone loss and posttraumatic osteoarthritis. CLINICAL RELEVANCE: Proteomic analysis of synovial fluid in patients with shoulder instability improved our understanding of this abnormality after an injury.


Asunto(s)
Biomarcadores , Moléculas de Adhesión Celular , Inestabilidad de la Articulación , Proteómica , Líquido Sinovial , Humanos , Líquido Sinovial/metabolismo , Líquido Sinovial/química , Inestabilidad de la Articulación/metabolismo , Femenino , Biomarcadores/metabolismo , Biomarcadores/análisis , Masculino , Moléculas de Adhesión Celular/metabolismo , Moléculas de Adhesión Celular/análisis , Adulto , Adulto Joven , Articulación del Hombro/metabolismo , Adolescente , Espectrometría de Masas en Tándem , Periostina
3.
Int J Urol ; 31(5): 475-482, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38193247

RESUMEN

OBJECTIVE: To investigate the clinicopathological factors affecting discrepancies between multi-parametric magnetic resonance imaging (mpMRI) and histopathological evaluation for diagnosis of extraprostatic extension (EPE) of prostate cancer. METHODS: One hundred-and-three lesions from 96 cases with suspected EPE on preoperative mpMRI, of which 60 and 43 showed bulging and frank capsular breach, respectively, were grouped according to pathological (p)EPE in radical prostatectomy specimens. Additionally, clinicopathological/immunohistochemical findings for periostin reflecting a desmoplastic stromal reaction were compared between these groups. RESULTS: pEPE was detected in 49 (48%) of the 103 lesions. Of these, 25 (42%) showed bulging and 24 (56%) showed frank capsular breach on MRI. In the total cohort, the absence of pEPE was significantly associated with a lower Gleason Grade Group (GG) (p < 0.0001), anterior location (p = 0.003), absence of intraductal carcinoma of the prostate (IDC-P) (p = 0.026), and high stromal periostin expression (p < 0.0001). These trends were preserved in subgroups defined by MRI findings, except for anterior location/IDC-P in the bulging subgroup. CONCLUSIONS: GG, anterior location, and periostin expression may cause mpMRI-pathological discrepancies regarding EPE. Periostin expression was a significant pEPE-negative factor in all subgroup analyses. Our results indicate that patients with suspected EPE on MRI, regardless of their pEPE results, should be followed as carefully as those with definite pEPE.


Asunto(s)
Imágenes de Resonancia Magnética Multiparamétrica , Prostatectomía , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/cirugía , Anciano , Persona de Mediana Edad , Próstata/patología , Próstata/diagnóstico por imagen , Moléculas de Adhesión Celular/análisis , Moléculas de Adhesión Celular/metabolismo , Clasificación del Tumor , Estudios Retrospectivos , Imagen por Resonancia Magnética
4.
Arch Gynecol Obstet ; 309(1): 167-173, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-36625879

RESUMEN

OBJECTIVE: It is aimed to be a technique that can be used for diagnosis and to prevent maternal deaths in cases where the serum levels of cell adhesion molecules are different in patients with abnormal placentation compared to healthy pregnant women. MATERIALS AND METHODS: Patients between March 2020 and September 2021 were included in the study. While 56 patients, out of 153 cases formed the placental adhesion and/or localization anomaly group, 55 cases without placental adhesion anomaly (placental invasion anomaly and/or previa pathology) constituted the cesarean section group and 42 cases constituted the vaginal birth control group. Demographic characteristics and histories of 153 patients were questioned. I-CAM-1, V-CAM-1, E-Selectin, P-Selectin, LRG-1 levels were studied. The parameters measured by the ELISA method were studied in the Thermo Fisher Scientific Multiscan Go (Finland) device at the Hatay Mustafa Kemal University Medical Faculty Medical Biochemistry USA ELISA Laboratory. Wholehouse and One Way Anova analysis methods were used to compare the results. RESULTS: There were significant differences in E-Selectin, P-Selectin, ICAM-1 and LRG-1 values between the groups (p < 0.05). There was a significant difference between the vaginal birth (VB) and previa/percreata (PP) groups in terms of E-Selectin (p = 0.038). In terms of P-Selectin, there was a significant difference between the C/S and previa/percreata (PP) groups (p < 001). P-Selectin was higher in the previa/percreata (PP) group. There was a significant difference between the Vaginally birth (VB), C/S group (p = 0.041) and the vaginal birth (VB), previa/percreata (PP) group (p = 0.013) in terms of ICAM-1, but there was no significant difference between the C/S and previa/percreata (PP) groups. In terms of LRG-1, there was a significant difference between all 3 groups (p < 0.05). DISCUSSION: A recent study investigated the potential modulatory effects of trans-resveratrol (RSV), arginase and endothelial dysfunction biomarkers in patients with PE. Another reflection of endothelial dysfunction in PE is increased endothelial activation biomarkers such as intercellular adhesion molecule-1 (ICAM-1), von Willebrand factor (vWF), and Caspase-3 (CASP-3). The study, regarding vWF expression, the preeclampsia (PE) group showed higher levels compared to endothelial cells incubated with healty pregnant (HP) plasma [Bueno-Pereira et al 2022 Antioxidants 2111]. From this and similar studies, the hypothesis that the role of cell adhesion molecules in endothelial damage may be the underlying cause of invasion and location anomalies emerges. This hypothesis is the starting point of our study. CONCLUSIONS: In our study, all adhesion molecules except V-CAM-1 were found to be significantly higher in the previa/percreata (PP) group. E-Selectin and LRG-1 adhesion molecules were found to be significantly higher even in C/S patients compared to normal delivery. As a result; these adhesion molecules can be studied as a marker in previa/percreata (PP) patients.


Asunto(s)
Preeclampsia , Molécula 1 de Adhesión Celular Vascular , Femenino , Humanos , Embarazo , Biomarcadores , Moléculas de Adhesión Celular/análisis , Cesárea , Selectina E/análisis , Células Endoteliales/química , Células Endoteliales/metabolismo , Células Endoteliales/patología , Molécula 1 de Adhesión Intercelular/análisis , Selectina-P , Placenta/patología , Preeclampsia/metabolismo , Factor de von Willebrand
5.
J Periodontal Res ; 59(3): 446-457, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38140743

RESUMEN

OBJECTIVE: The aim of this study was to analyze the effects of periodontal treatment on markers of atherosclerotic coronary artery disease and circulating levels of periostin. BACKGROUND: Periostin is necessary for periodontal stability, but it is highly present in atherosclerotic plaques. Treatment of periodontal disease, with low levels of local periostin, is thought to reduce systemic levels of periostin. Thus, this may contribute to cardiovascular health. METHODS: A pilot randomized controlled clinical trial was designed to include patients with severe periodontal disease and history of atherosclerotic coronary artery disease. Samples of gingival crevicular fluid (GCF) and serum were collected before and after periodontal treatment by periodontal surgery or non-surgical therapy. The levels of several markers of inflammation and cardiovascular damage were evaluated including CRP, IFN-γ, IL-1ß, IL-10, MIP-1α, periostin, and TNF-α in GCF and CRP, Fibrinogen, IFN-γ, IL-1ß, IL-6, IL-10, L-Selectin, MIP-1α, Periostin, TNF-α, and vWF in serum. RESULTS: A total of 22 patients with an average of 56 years old were recruited for participating in this study. Twenty of them were male. Most of them (82%) had suffered an acute myocardial event and underwent surgery for placing 1, 2, or 3 stents in the coronary arteries more than 6 months ago but less than 1 year. The treatment of periodontal disease resulted in an overall improvement of all periodontal parameters. Regarding the evaluation of GCF and serum, a significant increase of periostin in the GCF was observed after periodontal surgery. In contrast, although other markers in GCF and serum improved, no significant correlations were found. CONCLUSION: Treatment of periodontal disease through periodontal surgery induces a local and transient increase in the levels of periostin in the gingival crevicular fluid. The effects on systemic markers of inflammation and cardiovascular function have not been confirmed.


Asunto(s)
Biomarcadores , Moléculas de Adhesión Celular , Enfermedad de la Arteria Coronaria , Líquido del Surco Gingival , Enfermedades Periodontales , Humanos , Masculino , Proyectos Piloto , Persona de Mediana Edad , Femenino , Moléculas de Adhesión Celular/análisis , Moléculas de Adhesión Celular/sangre , Moléculas de Adhesión Celular/metabolismo , Enfermedad de la Arteria Coronaria/cirugía , Enfermedad de la Arteria Coronaria/complicaciones , Líquido del Surco Gingival/química , Líquido del Surco Gingival/metabolismo , Biomarcadores/análisis , Biomarcadores/sangre , Enfermedades Periodontales/metabolismo , Enfermedades Periodontales/complicaciones , Interleucina-10/análisis , Interleucina-10/sangre , Proteína C-Reactiva/análisis , Interferón gamma/análisis , Interferón gamma/sangre , Anciano , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-1beta/análisis , Interleucina-1beta/sangre , Interleucina-1beta/metabolismo , Periostina
6.
J Oral Pathol Med ; 52(2): 181-187, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36207782

RESUMEN

BACKGROUND: Primordial odontogenic tumour is a benign mixed neoplasm of recent description, which has histological similarities with other odontogenic tumours such as the ameloblastic fibroma. In this article, we investigate the architecture of the sub-epithelial layer of mesenchymal cells expressing the marker CD34 in primordial odontogenic tumour. OBJECTIVE: Analyse the spatial patterns of CD34 expression in primordial odontogenic tumour and compare them with those in ameloblastic fibroma and the normal tooth germ by means of objective imaging approaches, to better characterise these lesions. METHODS: Two cases of primordial odontogenic tumour, four cases of ameloblastic fibroma and two cases of tooth germ in cap and bell stages were used for morphological, structural and immunohistochemical analyses. RESULTS: CD34 expression was found in vascular endothelium of primordial odontogenic tumour, ameloblastic fibroma and tooth germ. In addition, a characteristic sub-epithelial expression was observed only in primordial odontogenic tumour, corresponding to 84%-86% of the sample boundaries. Moreover, the zone expressing CD34 corresponded with a higher cellularity, which was absent in ameloblastic fibroma and tooth germ. CONCLUSION: Image analysis of the primordial odontogenic tumour architecture revealed characteristics absent in other odontogenic tumours and tooth germs. This study provides additional information to support the idea that this neoplasm is a distinct entity from early stage AF or developing odontoma.


Asunto(s)
Fibroma , Tumores Odontogénicos , Odontoma , Humanos , Tumores Odontogénicos/patología , Germen Dentario , Odontoma/patología , Moléculas de Adhesión Celular/análisis
7.
Mol Biol Rep ; 49(12): 11881-11890, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36224445

RESUMEN

Diabetes patients are at a high risk of developing complications related to angiopathy and disruption of the signal transduction system. The liver is one of the multiple organs damaged during diabetes. Few studies have evaluated the morphological effects of adhesion factors in diabetic liver. The influence of diurnal variation has been observed in the expression and functioning of adhesion molecules to maintain tissue homeostasis associated with nutrient uptake. The present study demonstrated that the rhythm-influenced functioning of tight junction was impaired in the liver of ob/ob mice. The tight junctions of hepatocytes were loosened during the dark period in control mice compared to those in ob/ob mice, where the hepatocyte gaps remained open throughout the day. The time-dependent expression of zonula occludens 1 (ZO1, encoded by Tjp1 gene) in the liver plays a vital role in the functioning of the tight junction. The time-dependent expression of ZO1 was nullified and its expression was attenuated in the liver of ob/ob mice. ZO1 expression was inhibited at the mRNA and protein levels. The expression rhythm of ZO1 was found to be regulated by heat shock factor (HSF)1/2, the expression of which was reduced in the liver of ob/ob mice. The DNA-binding ability of HSF1/2 was decreased in the liver of ob/ob mice compared to that in control mice. These findings suggest the involvement of impaired expression and functioning of adhesion factors in diabetic liver complications.


Asunto(s)
Moléculas de Adhesión Celular , Uniones Estrechas , Proteína de la Zonula Occludens-1 , Animales , Ratones , Moléculas de Adhesión Celular/análisis , Hepatocitos/metabolismo , Hígado , Uniones Estrechas/química , Uniones Estrechas/genética , Uniones Estrechas/metabolismo , Proteína de la Zonula Occludens-1/genética , Proteína de la Zonula Occludens-1/análisis , Proteína de la Zonula Occludens-1/metabolismo
8.
Nanotechnology ; 33(42)2022 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-35820407

RESUMEN

EDIL3 is a strong and highly accurate diagnostic marker for breast cancer, meanwhile, EDIL3 overexpressed exosomes are novel biomarkers for the early diagnosis of triple-negative breast cancer (TNBC). Here, we proposed a fluorescent detection method for EDIL3 overexpressed exosomes, which is simple and sensitive. Basically, we utilized a magnetic nanospheres (MNS) based liquid sandwich immunoassay strategy. MNS were modified with CD63 aptamers, which can immunologically bound to the CD63 protein on the surface of exosomes. Alexa Fluor 647 labeled anti-EDIL3 antibodies (Anti-EDIL3/AF647) were used as the fluorescent probes to recognize the EDIL3 on exosomes derived from a TNBC cell line (MDA-MB-231). With the target TNBC exosomes present, sandwich structures containing MNS, exosomes and fluorescent probes were formed. After magnetic purification, optical super resolution imaging of the products was conducted to check the specificity of the assay. In addition, fluorescence signals of the products were detected to quantitatively analyze the EDIL3 overexpressed exosomes. The linear range was found to be 7.78 × 101to 7.78× 106particlesµl-1. The detection limit was approximately 10 particlesµl-1. The feasibility of the method for the detection of exosomes in complex biological samples was also demonstrated. Such a simple and sensitive detection method for EDIL3 overexpressed exosomes holds a great potential in clinical diagnosis of TNBC.


Asunto(s)
Exosomas , Neoplasias de la Mama Triple Negativas , Proteínas de Unión al Calcio/análisis , Proteínas de Unión al Calcio/metabolismo , Moléculas de Adhesión Celular/análisis , Moléculas de Adhesión Celular/metabolismo , Línea Celular Tumoral , Exosomas/química , Colorantes Fluorescentes/análisis , Humanos , Inmunoensayo , Imagen Óptica , Neoplasias de la Mama Triple Negativas/diagnóstico , Neoplasias de la Mama Triple Negativas/metabolismo
9.
Aging (Albany NY) ; 14(4): 1597-1610, 2022 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-35172279

RESUMEN

BACKGROUND: COVID-19 survivors report residual lung abnormalities after discharge from the hospital. The aim of this study was to identify biomarkers in serum and induced sputum samples from patients after hospitalization for COVID-19. METHODS: Patients admitted to hospitals in Spain with laboratory-confirmed COVID-19 were recruited for this study. SARS-CoV-2-infected patients were divided into groups with mild/moderate and severe disease according to the severity of their symptoms during hospitalization. Levels of 92 biomarkers were measured in serum and induced sputum samples. RESULTS: A total of 108 patients (46.2% severe cases) were included in this study. The median number of days after the onset of symptoms was 104. A significant difference was observed in diffusing capacity for carbon monoxide (DLCO), an indicator of lung function, whereby DLCO <80% was significantly lower in severe cases (p <0.001). Differences in inflammatory biomarkers were observed between patients with mild/moderate and severe disease. For some biomarkers, correlations in serum and induced sputum levels were detected. Independent predictors of severe disease were DLCO <80% and the serum CDCP1 value. CONCLUSIONS: Higher levels of CDCP1 remain after hospital discharge and are associated with the severity of COVID-19. The possible prognostic implications warrant further investigation.


Asunto(s)
Antígenos de Neoplasias/sangre , COVID-19/sangre , Moléculas de Adhesión Celular/sangre , Antígenos de Neoplasias/análisis , Biomarcadores/sangre , Moléculas de Adhesión Celular/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Esputo/química
10.
J Clin Lab Anal ; 36(2): e24179, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35152510

RESUMEN

BACKGROUND: Periostin (POSTN) is an extracellular matrix protein that is overexpressed in lung cancer and is considered an effective diagnostic and prognostic biomarker for lung cancer. The purpose of this study was to investigate the diagnostic performance of POSTN and to further evaluate the diagnostic value of POSTN combined with carcinoembryonic antigen (CEA) and cancer ratio [CR: serum lactate dehydrogenase (LDH)/pleural effusion adenosine deaminase (PE ADA)] in lung cancer-related malignant PE (MPE). METHODS: A total of 108 patients with PE, including 54 with lung cancer and 54 with benign lung disease, were enrolled in this study. The POSTN levels of PE and serum were detected using an enzyme-linked immunosorbent assay. Information on the expression of PE and serum CEA, serum LDH, and PE ADA was collected from medical records. RESULTS: The levels of PE POSTN in MPE of patients with lung cancer were significantly higher than those in patients with benign PE (p < 0.0001). The receiver operating characteristic (ROC) curve indicated that the diagnostic sensitivity and specificity of PE POSTN for lung cancer-related MPE were respectively 77.78% and 68.52% when the cutoff value was determined to be 53.45 ng/ml. The ROC curve analysis demonstrated that PE POSTN has a high diagnostic value in MPE associated with lung cancer [area under the curve (AUC) = 0.764], and the combination of PE POSTN, PE CEA, and CR can improve the diagnostic accuracy of lung cancer-related MPE (AUC = 0.948). CONCLUSION: POSTN can be used as a potential marker for lung cancer-related MPE diagnosis.


Asunto(s)
Biomarcadores de Tumor/análisis , Moléculas de Adhesión Celular/análisis , Neoplasias Pulmonares/complicaciones , Derrame Pleural Maligno/diagnóstico , Anciano , Líquido del Lavado Bronquioalveolar/química , Moléculas de Adhesión Celular/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Derrame Pleural/diagnóstico , Derrame Pleural Maligno/química , Derrame Pleural Maligno/etiología , Curva ROC , Sensibilidad y Especificidad
11.
Med Sci (Basel) ; 11(1)2022 12 29.
Artículo en Inglés | MEDLINE | ID: mdl-36649044

RESUMEN

BACKGROUND: Knowledge about the occurrence of processes such as proliferation, apoptosis and angiogenesis in healthy lung tissues with different bronchial epitheliums is limited, and further exploration can contribute to a better understanding of the physiological renewal of lung tissues. The processes mentioned above occur with the help of important tissue factors; therefore, the aim of the study was to determine the expression of markers Ki-67, nestin, CD34 and vascular endothelial growth factor (VEFG) and detect apoptotic cells in relatively healthy lung tissue. METHODS: Samples of relatively healthy lung tissue were obtained from 19 patients and divided into groups of patients with non-changed and patients with metaplastic bronchial epithelium. Tissue samples were examined by hematoxylin and eosin staining. Ki-67, nestin, VEGF and CD34-positive cells were detected by the immunohistochemistry method. Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay was carried out to detect apoptotic cells. The number of positive structures was counted semi-quantitatively by microscopy. RESULTS: Ki-67-positive cells were detected in only one case. An occasional to moderate number of nestin-positive structures was found in various tissues of relatively healthy lungs with different bronchial epitheliums. No apoptotic cells were seen in non-changed bronchial epithelium, compared with few apoptotic cells in metaplastic bronchial epithelium. Metaplastic bronchial epithelium contained more VEGF-positive cells than non-changed bronchial epithelium. Samples with non-changed, and metaplastic bronchial epithelium both contained a similar number of CD34-positive structures. CONCLUSIONS: Proliferative activity and programmed cell death are not prominent events in normal lung tissue. A moderate number of nestin-positive cells in the alveolar epithelium and cartilage of bronchi with pseudostratified ciliated epithelium suggests a significant role of neuronal origin cells in these structures, to be intensified in metaplastic bronchial epithelium. A practically non-changed number of CD34-positive cells excludes any difference in stimulation of endothelial origin cells between lungs with different types of epithelium, while an increase in VEGF in structures with metaplastic epithelium suggests the presence/influence of tissue ischemia impact on possible development/maintenance of metaplasia.


Asunto(s)
Pulmón , Factor A de Crecimiento Endotelial Vascular , Humanos , Apoptosis , Moléculas de Adhesión Celular/análisis , Epitelio/química , Epitelio/metabolismo , Antígeno Ki-67/análisis , Pulmón/metabolismo , Metaplasia , Nestina/análisis , Factor A de Crecimiento Endotelial Vascular/análisis , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factores de Crecimiento Endotelial Vascular/análisis , Antígenos CD34
12.
Future Oncol ; 18(3): 333-348, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34756116

RESUMEN

Background: Papillary thyroid carcinoma (PTC) is one of the most common endocrine malignancies and has a favorable prognosis. However, optimal treatments and prognostic markers have not been clearly identified. Methods: Gene expression data from primary PTC were downloaded from the Gene Expression Omnibus database and subjected to two analyses of differentially expressed genes (DEGs), followed by intersecting individual and integrated DEGs analyses as well as gene set enrichment analysis. Analysis of data from Sequence Read Archive and The Cancer Genome Atlas, immunohistochemistry and qRT-PCR of TFF3 were performed to validate the results. Finally, the relationship between gene expression and disease-free survival as well as immune cell infiltration were investigated. Results: Six critical DEGs and several tumor-enriched signaling pathways were identified. Immunohistochemistry and qRT-PCR validated the low expression of TFF3 in PTC. TFF3 and FCGBP are coexpressed in PTC, and patients with lower gene expression had worse disease-free survival but higher immune cell infiltration. Conclusion: TFF3 was significantly underexpressed and may function with FCGBP synergistically in PTC.


Lay abstract Thyroid cancers are some of the most common endocrine malignancies. However, the optimal treatments and prognostic markers have not been clearly identified. We identified six critical differentially expressed genes and several tumor-enriched signaling pathways in papillary thyroid carcinoma, and found that TFF3 was the most underexpressed gene, as validated by experiment. In addition, TFF3 and FCGBP worked synergistically and may mark prognosis and tumor immune cell infiltration, which may benefit patients with papillary thyroid carcinoma by providing early indication and prompting further basic investigation.


Asunto(s)
Biomarcadores de Tumor/genética , Recurrencia Local de Neoplasia/epidemiología , Cáncer Papilar Tiroideo/mortalidad , Neoplasias de la Tiroides/mortalidad , Factor Trefoil-3/genética , Adulto , Biomarcadores de Tumor/análisis , Moléculas de Adhesión Celular/análisis , Moléculas de Adhesión Celular/genética , Conjuntos de Datos como Asunto , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/inmunología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Medición de Riesgo/métodos , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/inmunología , Cáncer Papilar Tiroideo/cirugía , Glándula Tiroides/inmunología , Glándula Tiroides/patología , Glándula Tiroides/cirugía , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/inmunología , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Factor Trefoil-3/análisis , Microambiente Tumoral/inmunología
13.
Front Immunol ; 12: 753929, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34950135

RESUMEN

Background: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) mediated by autoimmunity. No objective clinical indicators are available for the diagnosis and prognosis of MS. Extracellular proteins are most glycosylated and likely to enter into the body fluid to serve as potential biomarkers. Our work will contribute to the in-depth study of the functions of extracellular proteins and the discovery of disease biomarkers. Methods: MS expression profiling data of the human brain was downloaded from the Gene Expression Omnibus (GEO). Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases. GO and KEGG were used to analyze the function and pathway of EP-DEGs. STRING, Cytoscape, MCODE and Cytohubba were used to construct a protein-protein interaction (PPI) network and screen key EP-DEGs. Key EP-DEGs levels were detected in the CSF of MS patients. ROC curve and survival analysis were used to evaluate the diagnostic and prognostic ability of key EP-DEGs. Results: We screened 133 EP-DEGs from DEGs. EP-DEGs were enriched in the collagen-containing extracellular matrix, signaling receptor activator activity, immune-related pathways, and PI3K-Akt signaling pathway. The PPI network of EP-DEGs had 85 nodes and 185 edges. We identified 4 key extracellular proteins IL17A, IL2, CD44, IGF1, and 16 extracellular proteins that interacted with IL17A. We clinically verified that IL17A levels decreased, but Del-1 and resolvinD1 levels increased. The diagnostic accuracy of Del-1 (AUC: 0.947) was superior to that of IgG (AUC: 0.740) with a sensitivity of 82.4% and a specificity of 100%. High Del-1 levels were significantly associated with better relapse-free and progression-free survival. Conclusion: IL17A, IL2, CD44, and IGF1 may be key extracellular proteins in the pathogenesis of MS. IL17A, Del-1, and resolvinD1 may co-regulate the development of MS and Del-1 is a potential biomarker of MS. We used bioinformatics methods to explore the biomarkers of MS and validated the results in clinical samples. The study provides a theoretical and experimental basis for revealing the pathogenesis of MS and improving the diagnosis and prognosis of MS.


Asunto(s)
Líquido Extracelular/química , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Proteínas/análisis , Adulto , Biomarcadores , Química Encefálica , Proteínas de Unión al Calcio/análisis , Proteínas de Unión al Calcio/fisiología , Moléculas de Adhesión Celular/análisis , Moléculas de Adhesión Celular/fisiología , Proteínas del Líquido Cefalorraquídeo/análisis , Proteínas del Líquido Cefalorraquídeo/genética , Conjuntos de Datos como Asunto , Supervivencia sin Enfermedad , Femenino , Perfilación de la Expresión Génica , Ontología de Genes , Cefalea/genética , Cefalea/metabolismo , Humanos , Interleucina-17/análisis , Interleucina-17/fisiología , Masculino , Persona de Mediana Edad , Anotación de Secuencia Molecular , Esclerosis Múltiple Recurrente-Remitente/líquido cefalorraquídeo , Esclerosis Múltiple Recurrente-Remitente/genética , Esclerosis Múltiple Recurrente-Remitente/metabolismo , Supervivencia sin Progresión , Análisis por Matrices de Proteínas , Mapas de Interacción de Proteínas , Proteínas/genética , Sensibilidad y Especificidad
14.
Diagn Pathol ; 16(1): 86, 2021 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-34563225

RESUMEN

BACKGROUND: Thyroid tumors are often difficult to histopathologically diagnose, particularly follicular adenoma (FA) and follicular carcinoma (FC). Papillary carcinoma (PAC) has several histological subtypes. Periostin (PON), which is a non-collagenous extracellular matrix molecule, has been implicated in tumor invasiveness. We herein aimed to elucidate the expression status and localization of PON in thyroid tumors. METHOD: We collected 105 cases of thyroid nodules, which included cases of adenomatous goiter, FA, microcarcinoma (MIC), PAC, FC, poorly differentiated carcinoma (PDCa), and undifferentiated carcinoma (UCa), and immunohistochemically examined the PON expression patterns of these lesions. RESULTS: Stromal PON deposition was detected in PAC and MIC, particularly in the solid/sclerosing subtype, whereas FA and FC showed weak deposition on the fibrous capsule. However, the invasive and/or extracapsular regions of microinvasive FC showed quite strong PON expression. Except for it, we could not find any significant histopathological differences between FA and FC. There were no other significant histopathological differences between FA and FC. Although PDCa showed a similar PON expression pattern to PAC, UCa exhibited stromal PON deposition in its invasive portions and cytoplasmic expression in its carcinoma cells. Although there was only one case of UCa, it showed strong PON immunopositivity. PAC and MIC showed similar patterns of stromal PON deposition, particularly at the invasive front. CONCLUSIONS: PON may play a role in the invasion of thyroid carcinomas, particularly PAC and UCa, whereas it may act as a barrier to the growth of tumor cells in FA and minimally invasive FC.


Asunto(s)
Adenoma/química , Biomarcadores de Tumor/análisis , Carcinoma Papilar/química , Moléculas de Adhesión Celular/análisis , Bocio/metabolismo , Inmunohistoquímica , Cáncer Papilar Tiroideo/química , Neoplasias de la Tiroides/química , Nódulo Tiroideo/química , Adenoma/patología , Adolescente , Adulto , Anciano , Carcinoma Papilar/patología , Diferenciación Celular , Femenino , Bocio/patología , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Valor Predictivo de las Pruebas , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología , Nódulo Tiroideo/patología , Adulto Joven
15.
BMC Cancer ; 21(1): 1011, 2021 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-34503477

RESUMEN

BACKGROUND: Flow cytometry plays a key role in detecting bone marrow (BM) involvement in patients with diffuse large B-cell lymphoma (DLBCL). To improve its detection sensitivity, we need to explore novel markers. In this study, we detected the expression CD54 on lymphoma cells in BM specimens from DLBCL patients and clarified its diagnostic significance in BM involvement by DLBCL. METHODS: We collected BM specimens from 76 patients with DLBCL (germinal center B-cell (GCB) = 25, non-GCB = 51) and 10 control patients without lymphoma. We detected and compared the expression of CD54 on lymphoma cells and normal mature B cells by using 10-color panels. RESULTS: Normal plasma cells expressed a higher level of CD54 as compared with hematogones (p < 0.05) and normal mature B cells (p < 0.05). Among 76 patients, 23 of them (GCB = 12, non-GCB = 11) had BM involvement. Lymphoma B cells from 12 cases (GBC = 4, non-GCB = 8) expressed a higher level of CD54 compared to normal mature B cells (p < 0.05). Additionally, lymphoma cells of the non-GCB subtype frequently expressed a higher level of CD54 in comparison to the GCB subtype (p < 0.05). And the high expression of CD54 was not related to plasmacytoid differentiation. CONCLUSION: Aberrant expression of CD54 on lymphoma cells is frequently seen in patients' BM specimens involved by DLBCL, especially in the non-GCB subtype. CD54 could be used as a new marker to gate on lymphoma cells and improve the detection sensitivity of BM involvement in patients with DLBCL.


Asunto(s)
Biomarcadores de Tumor/análisis , Médula Ósea/química , Citometría de Flujo , Molécula 1 de Adhesión Intercelular/análisis , Linfoma de Células B Grandes Difuso/química , Adulto , Anciano , Anciano de 80 o más Años , Linfocitos B/química , Linfocitos B/metabolismo , Biomarcadores de Tumor/metabolismo , Biopsia , Médula Ósea/metabolismo , Médula Ósea/patología , Moléculas de Adhesión Celular/análisis , Moléculas de Adhesión Celular/metabolismo , Diferenciación Celular , Femenino , Centro Germinal/química , Centro Germinal/metabolismo , Centro Germinal/patología , Humanos , Inmunofenotipificación , Molécula 1 de Adhesión Intercelular/metabolismo , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Células Plasmáticas/citología
16.
Cell Mol Biol Lett ; 26(1): 31, 2021 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-34217213

RESUMEN

Developmental endothelial locus-1 (Del-1) is a secretory, multifunctional domain protein. It can bind to integrins and phosphatidylserine. As a local tissue signal, it plays a regulatory role in the cancer microenvironment and inflammation. Del-1 has destructive effects in most cancers and is associated with the progression and invasion of some cancers. In contrast, Del-1 also plays a protective role in inflammation. Del-1 regulates inflammation by regulating the generation of neutrophils in bone marrow, inhibiting the recruitment and migration of neutrophils and accelerating the clearance of neutrophils by macrophages. Del-1 and IL-17 are reciprocally regulated, and their balance maintains immune system homeostasis. Del-1 is expected to become a new therapeutic target for inflammatory disorders such as multiple sclerosis.


Asunto(s)
Proteínas de Unión al Calcio/metabolismo , Moléculas de Adhesión Celular/metabolismo , Inflamación/metabolismo , Neoplasias/metabolismo , Animales , Proteínas de Unión al Calcio/análisis , Moléculas de Adhesión Celular/análisis , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Humanos , Inflamación/patología , Macrófagos/metabolismo , Macrófagos/patología , Neoplasias/patología , Neutrófilos/metabolismo , Neutrófilos/patología
17.
BMC Nephrol ; 22(1): 266, 2021 07 16.
Artículo en Inglés | MEDLINE | ID: mdl-34271871

RESUMEN

BACKGROUND: To investigate if remote ischemic preconditioning (RIPC) can offer any renoprotective value by counteracting the deleterious effect of partial nephrectomy (PN) under warm ischemia on renal function. METHODS: Four groups, each with 5 Wistar albino rats, were constructed; RIPC + PN, PN, RIPC and sham. Right nephrectomy was performed to constitute a solitary kidney model. RIPC denoted sequential clamping/declamping of the femoral artery/vein complex. PN was performed under warm-ischemia following RIPC. Blood samples were collected on multiple occasions until euthanasia on day 7. Immunoassays were conducted to measure the serum and tissues levels of kidney injury markers. Kidneys were examined histologically and morphometric analyzes were performed using digital scanning. RESULTS: IL-33 levels did not differ significantly between the groups. Serum levels of KIM-1, NGAL, and aldose reductase in RIPC + PN, PN and RIPC groups were significantly lower than that of sham group. Tissue biomarker levels were similar across groups. The observed trend in mean necrosis area of PN group was higher than that of RIPC + PN group (p > 0.05). The transitional zone between necrosis and healthy tissue showed a trend towards increasing width in the rats subjected to RIPC before PN vs. those who underwent PN without RIPC (p > 0.05). CONCLUSION: RIPC failed to counteract the renal functional consequences of PN under warm ischemia in a solitary kidney animal model. The supportive but marginal histological findings in favor of RIPC's renoprotective potential were not supplemented with the changes in serum and tissue biomarker levels.


Asunto(s)
Moléculas de Adhesión Celular/análisis , Precondicionamiento Isquémico/métodos , Riñón , Lipocalina 2/análisis , Nefrectomía , Daño por Reperfusión , Aldehído Reductasa/análisis , Animales , Biomarcadores/análisis , Modelos Animales de Enfermedad , Riñón/metabolismo , Riñón/patología , Riñón/fisiopatología , Pruebas de Función Renal , Nefrectomía/efectos adversos , Nefrectomía/métodos , Ratas , Ratas Wistar , Daño por Reperfusión/sangre , Daño por Reperfusión/etiología , Daño por Reperfusión/patología , Resultado del Tratamiento , Isquemia Tibia/métodos
18.
J Invest Dermatol ; 141(10): 2380-2390, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33865912

RESUMEN

Little is known regarding the molecular differences between basal cell carcinoma (BCC) subtypes, despite clearly distinct phenotypes and clinical outcomes. In particular, infiltrative BCCs have poorer clinical outcomes in terms of response to therapy and propensity for dissemination. In this project, we aimed to use exome sequencing and RNA sequencing to identify somatic mutations and molecular pathways leading to infiltrative BCCs. Using whole-exome sequencing of 36 BCC samples (eight infiltrative) combined with previously reported exome data (58 samples), we determine that infiltrative BCCs do not contain a distinct somatic variant profile and carry classical UV-induced mutational signatures. RNA sequencing on both datasets revealed key differentially expressed genes, such as POSTN and WISP1, suggesting increased integrin and Wnt signaling. Immunostaining for periostin and WISP1 clearly distinguished infiltrative BCCs, and nuclear ß-catenin staining patterns further validated the resulting increase in Wnt signaling in infiltrative BCCs. Of significant interest, in BCCs with mixed morphology, infiltrative areas expressed WISP1, whereas nodular areas did not, supporting a continuum between subtypes. In conclusion, infiltrative BCCs do not differ in their genomic alteration in terms of initiating mutations. They display a specific type of interaction with the extracellular matrix environment regulating Wnt signaling.


Asunto(s)
Carcinoma Basocelular/genética , Neoplasias Cutáneas/genética , Anciano , Proteínas CCN de Señalización Intercelular/análisis , Carcinoma Basocelular/clasificación , Carcinoma Basocelular/patología , Moléculas de Adhesión Celular/análisis , Femenino , Humanos , Masculino , Mutación , Proteínas Proto-Oncogénicas/análisis , Neoplasias Cutáneas/clasificación , Neoplasias Cutáneas/patología
19.
J Crohns Colitis ; 15(10): 1707-1719, 2021 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-33837762

RESUMEN

BACKGROUND: Real life data regarding pharmacokinetics of vedolizumab in patients needing dose optimisation are scarce. We set to examine whether pre-optimisation vedolizumab levels associate with therapy outcomes and which mechanisms explain the associations. METHODS: A multicentre observational study assessed the outcome of dose increase in association with pre-escalation levels in vedolizumab-treated patients. SubsequentIy, α4ß7 occupancy on peripheral blood [PB] and intestinal lamina propria [LP] tissues was investigated on various cellular subsets in patients undergoing lower endoscopy on infusion day. Cellular localisation of vedolizumab-bound α4ß7 and effects on M1 and M2 macrophages were also explored. RESULTS: A total of 161 inflammatory bowel disease [IBD] patients were included. Among 129/161 patients intensified during maintenance [Week 14 onward], pre-intensification trough levels were comparable or higher among those subsequently attaining post-optimisation clinical, biomarker, and endoscopic remission, compared with non-remitting patients [p = 0.09, 0.25, 0.04, respectively]. Similar results were demonstrated for those dose-optimised during induction [Week 6, n = 32]. In the immune sub-study [n = 43], free α4ß7 receptors at trough were similarly low among patients with/without mucosal healing, on PB T cells [p = 0.15], LP T cells [p = 0.88], and on PB eosinophils [p = 0.08]. Integrin receptors on M1 and M2 macrophages were also saturated by low levels of vedolizumab and anti-inflammatory cytokine secretion was not increased. Co-localisation and dissociation experiments demonstrated membranal α4ß7 receptors of two origins: non-internalised and newly generated α4ß7, but re-binding was still complete at very low concentrations. CONCLUSIONS: These results do not support pharmacokinetics as the mechanism responsible for loss of response to vedolizumab, nor do they support a need for higher drug concentration to enhance vedolizumab's immune effects. Higher pre-escalation levels may indicate less clearance [less severe disease] and higher likelihood of subsequent re-gained response, regardless of therapy escalation.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Fármacos Gastrointestinales/administración & dosificación , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Adulto , Biomarcadores/análisis , Proteína C-Reactiva/análisis , Moléculas de Adhesión Celular/análisis , Relación Dosis-Respuesta a Droga , Endoscopía Gastrointestinal , Femenino , Humanos , Macrófagos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Mucoproteínas/análisis , Albúmina Sérica/análisis
20.
Cancer Med ; 10(6): 2063-2074, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33624385

RESUMEN

AIMS: To investigate novel biomarker for diagnosis of cervical cancer, we analyzed the datasets in Gene Expression Omnibus (GEO) and confirmed the candidate biomarker in patient sample. MATERIALS AND METHODS: We collected major datasets of cervical cancer in GEO, and analyzed the differential expression of normal and cancer samples online with GEO2R and tested the differences, then focus on the GSE63514 to screen the target genes in different histological grades by using the R-Bioconductor package and R-heatmap. Then human specimens from the cervix in different histological grades were used to confirm the top 8 genes expression by immunohistochemical staining using Ki67 as a standard control. RESULTS: We identified genes differentially expressed in normal and cervical cancer, 274 upregulated genes and 206 downregulated genes. After intersection with GSE63514, we found the obvious tendency in different histological grades. Then we screened the top 24 genes, and confirmed the top 8 genes in human cervix tissues. Immunohistochemical (IHC) results confirmed that keratin 17 (KRT17) was not expressed in normal cervical tissues and was over-expressed in cervical cancer. Cysteine-rich secretory protein-2 (CRISP2) was less expressed in high-grade squamous intraepithelial lesions (HSILs) than in other histological grades. CONCLUSION: For the good repeatability and consistency of KRT17 and CRISP2, they may be good candidate biomarkers. Combined analysis of KRT17, CRISP2 expression at both genetic and protein levels can determine different histological grades of cervical squamous cell carcinoma. Such combined analysis is capable of improving diagnostic accuracy of cervical cancer.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , Moléculas de Adhesión Celular/genética , Queratina-17/genética , Displasia del Cuello del Útero/genética , Neoplasias del Cuello Uterino/genética , Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/patología , Moléculas de Adhesión Celular/análisis , Proteínas de Ciclo Celular/análisis , Proteínas de Ciclo Celular/genética , Cuello del Útero/metabolismo , Proteínas de Unión al ADN/análisis , Proteínas de Unión al ADN/genética , Bases de Datos Genéticas , Conjuntos de Datos como Asunto , Desmogleína 1/análisis , Desmogleína 1/genética , Regulación hacia Abajo , Femenino , Perfilación de la Expresión Génica/métodos , Marcadores Genéticos , Humanos , Inmunohistoquímica , Péptidos y Proteínas de Señalización Intracelular/análisis , Péptidos y Proteínas de Señalización Intracelular/genética , Queratina-17/análisis , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Clasificación del Tumor , Proteínas de Neurofilamentos/análisis , Proteínas de Neurofilamentos/genética , Proteínas y Péptidos Salivales/análisis , Proteínas y Péptidos Salivales/genética , Proteínas de Plasma Seminal/análisis , Proteínas de Plasma Seminal/genética , Regulación hacia Arriba , Neoplasias del Cuello Uterino/química , Neoplasias del Cuello Uterino/patología , Displasia del Cuello del Útero/química , Displasia del Cuello del Útero/patología
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