Search

Soluble major histocompatibility complex class I-related chain A molecules (sMICA) and natural-killer group 2 member D (NKG2D) not only correlate with tumorigenesis and progression, but also with tumor invasion and metastasis. In this study, we used immunohistochemistry to investigate the correlation and prognostic significance of the differential expression of sMICA and NKG2D in pancreatic carcinoma and paracarcinoma tissues from 70 patients with pancreatic carcinomas. The results showed that sMICA expression was significantly (P<0.05) higher in tumor tissues (67.1%) than that in adjacent nontumor tissues (31.4%), whereas NKG2D expression was significantly (P<0.001) lower in tumor tissues (32.9%) than that in adjacent nontumor tissues (60.0%). Spearman's rank correlation test showed a negative correlation between the expression of sMICA and that of NKG2D (r=-0.676, P<0.001). Kaplan-Meier survival analysis showed that a high sMICA expression was significantly correlated with decreased disease-free survival (DFS) (P<0.001) and overall survival (OS) (P<0.001), while a high NKG2D expression was significantly associated with increased DFS (P=0.001) and OS (P=0.001) of the patients. Multivariate analysis showed that a high sMICA expression was an independent predictive factor for poor DFS (P<0.001) and OS (P=0.012); but low NKG2D expression was not an independent prognostic factor for poor DFS (P=0.238) and OS (P=0.574). In conclusion, our findings suggest that the expression levels of sMICA and NKG2D are abnormal and negatively correlated with one another in pancreatic carcinoma tissues; they may be considered as valuable biomarkers for the prognosis of pancreatic carcinoma. [ABSTRACT FROM AUTHOR]

Previous research reported associations between bisphenol A (BPA) exposure and some malignant tumor incidences, yet the underlying mechanism remains largely uncertain. This investigation was aimed to explore the association of BPA exposure burden with colorectal cancer (CRC) and the role of tumor tissue lipid metabolism in the associations between BPA and CRC using lipidomic approach. Urinary BPA levels in CRC cases were significantly higher than those in controls (P value < 0.05). BPA was positively correlated with all three serum CRC biomarkers, with an estimated odds ratio (OR) of 4.45 (95% confidence interval (95% CI): [1.31, 15.14]) between the highest and lowest tertiles of exposure. Lipidomic screening of tumor samples suggested significant perturbation in the glycerophospholipid metabolism pathway, of which phosphatidylcholine (PC 34:0), phosphatidylcholine (PC 37:1), phosphatidylethanolamine (PE 34:2), triacylglycerol (TG 56:4) demonstrated mediation contribution of 21.9%, 18.7%, 18.4% and 27.39%, respectively, in the association between BPA exposure and CRC. Our work provides novel findings that cancer tissue metabolites may be playing vital mediating roles in the associations between BPA exposure burden and CRC risk. These findings contribute to better understanding of the etiology of CRC induced by environmental stressors. [Display omitted] • BPA exposure was associated with risk of CRC. • High BPA group exhibited significant lipid dysregulation in CRC tissues. • Lipid metabolites may mediate the association between BPA exposure and CRC. [ABSTRACT FROM AUTHOR]

Background The purpose of the present study was to examine the expression levels of microRNA-9 (miR- 9) in osteosarcoma tissues and normal bone tissues, and investigate the relationships between miR-9 expression, clinicopathological features and the prognosis of patients with osteosarcoma. Methods The expression levels of miR-9 in osteosarcoma tissues and corresponding non-cancerous tissues were detected using a real-time quantitative assay. Differences in patient survival were determined using the Kaplan-Meier method and a log-rank test. A Cox proportional hazards regression analysis was used for univariate and multivariate analyses of prognostic values. Results Compared to non-cancerous bone tissues, the expression levels of miR-9 in osteosarcoma tissues were significantly elevated (P < 0.001). We found that the expression level of miR-9 was significantly associated with tumor size (P = 0.011), clinical stage (P = 0.009) and distant metastasis (P < 0.001). The Kaplan-Meier curve showed that patients with low miR-9 expression survived significantly longer than patients with high miR-9 expression (P = 0.0017). Multivariate analysis suggested that miR-9 expression level (P = 0.002) is an independent prognostic factors for overall survival. Conclusions The findings of our study suggest that increased miR-9 expression has a strong correlation with the aggressive progression of osteosarcoma and its overexpression is a statistically significant risk factor affecting overall survival, suggesting that increased miR-9 expression could be a valuable marker of tumor progression and for prognosis of osteosarcoma. [ABSTRACT FROM AUTHOR]

Biliary tract cancers (BTCs) are lethal malignancies currently lacking satisfactory methods for early detection and accurate diagnosis. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) is a promising diagnostic tool for this disease. In this pilot study, sera samples from 50 BTCs and 30 cholelithiasis patients as well as 30 healthy subjects from a population-based case-control study were randomly grouped into training set (30 BTCs, 20 cholelithiasis and 20 controls), duplicate of training set, and blind set (20 BTCs, 10 cholelithiasis and 10 controls); all sets were analyzed on Immobilized Metal Affinity Capture ProteinChips via SELDI-TOF-MS. A decision tree classifier was built using the training set and applied to all test sets. The classification tree constructed with the 3,400, 4,502, 5,680, 7,598, and 11,242 mass-to-charge ratio (m/z) protein peaks had a sensitivity of 96.7% and a specificity of 85.0% when comparing BTCs with non-cancers. When applied to the duplicate set, sensitivity was 66.7% and specificity was 70.0%, while in the blind set, sensitivity was 95.0% and specificity was 75.0%. Positive predictive values of the training, duplicate, and blind sets were 82.9%, 62.5% and 79.2%, respectively. The agreement of the training and duplicate sets was 71.4% (Kappa = 0.43, u = 3.98, P < 0.01). The coefficient of variations based on 10 replicates of one sample for the five differential peaks were 15.8-68.8% for intensity and 0-0.05% for m/z. These pilot results suggest that serum protein profiling by SELDI-TOF-MS may be a promising approach for identifying BTCs but low assay reproducibility may limit its application in clinical practice. [ABSTRACT FROM AUTHOR]

Studies examining the regulatory roles and clinical applications of monosaccharides other than glucose in cancer have been neglected. Mannose, a common type of monosaccharide found in human body fluids and tissues, primarily functions in protein glycosylation rather than carbohydrate metabolism. Recent research has demonstrated direct anticancer effects of mannose in vitro and in vivo. Simply supplementing cell culture medium or drinking water with mannose achieved these effects. Moreover, mannose enhances the effectiveness of current cancer treatments including chemotherapy, radiotherapy, targeted therapy, and immune therapy. Besides the advancements in basic research on the anticancer effects of mannose, recent studies have reported its application as a biomarker for cancer or in the delivery of anticancer drugs using mannose-modified drug delivery systems. This review discusses the progress made in understanding the regulatory roles of mannose in cancer progression, the mechanisms underlying its anticancer effects, and its current application in cancer diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Objectives: To detect whether early growth response 1 (EGR1) in peripheral blood leucocytes (PBLs) indicates temporomandibular joint (TMJ) osteoarthritis (OA) lesions. Materials and Methods: Egr1 mRNA expression levels in PBLs were detected in eight malocclusion patients without temporomandibular disorder (TMD) signs and 16 malocclusion patients with clinical TMD signs with (eight) or without (eight) imaging signs of TMJ OA. Twelve 6‐week‐old rats were randomized to a control group and a unilateral anterior crossbite (UAC) group and were sampled at 4 weeks. The Egr1 mRNA expression levels in PBLs and protein expression levels in different orofacial tissues were measured. Results: Patients with TMD signs with/without TMJ OA diagnosis showed lower Egr1 mRNA expression levels in PBLs than patients without TMD signs. The lower Egr1 mRNA expression was also found in the PBLs of UAC rats, which were induced to exhibit early histo‐morphological signs of TMJ OA lesions. In subchondral bone of UAC rats, EGR1 protein expression was decreased, co‐localization of EGR1 with osterix or dentin matrix protein‐1 was identified, and the number of EGR1 and osterix double‐positive cells was reduced (all p < .05). Conclusion: Egr1 reduction in PBLs potentially indicates subchondral bone OA lesions at an early stage. [ABSTRACT FROM AUTHOR]

Summary: Background: The temporomandibular joint (TMJ) disc plays a role in joint movement and in load absorbance and distribution. An experimental unilateral anterior crossbite (UAC) prosthesis induces mandibular condylar cartilage degeneration in rats. However, the changes in the articular disc are still unknown. Objective: To describe changes in the TMJ discs of UAC rats. Methods: The discs of fifty‐four Sprague‐Dawley rats, equally distributed into a UAC group and an age‐matched sham‐operated control group at 4, 12 and 20 weeks (n = 9), were evaluated by gross and histomorphological observation and by detection at the mRNA or protein expression levels of the markers related to the matrix elements. Results: No macro‐ or micro‐morphological differences were observed between groups. However, there were catabolic degradative changes at the molecular level in the UAC group, showing a significant reduction in the mRNA and/or protein expression levels of many molecules. The reduction became worse with time (P < 0.05). The reduced molecules included: (a) those related to the extracellular matrix, such as type I collagen, decorin and fibromodulin; (b) those related to chondrogenesis, such as type II collagen and aggrecan; and (c) those related to osteogenesis, such as alkaline phosphatase and runt‐related transcription factor 2. The mRNA expression of vascular endothelial growth factor did not change. In contrast, fibronectin, which can promote wound healing, and its N‐terminal fragment, which can induce cartilage degradation, were accumulated (P < 0.05). Conclusion: TMJ discs were stimulated to catabolic changes by the aberrant dental occlusion and seemed to go to inanimate with time. [ABSTRACT FROM AUTHOR]

The aim of the present study was to screen out the biomarkers associated with chemoresistance in ovarian carcinomas and to investigate the molecular mechanisms. microRNA (miRNA) expression data was obtained from published microarray data of the GSE43867 dataset from Gene Expression Omnibus (GEO), including the data of 86 chemotherapy-treated patients with serous epithelial ovarian carcinomas (response group, 36 complete response cases and 12 partial response cases; non-response group, 10 stable cases and 28 progressive disease cases), and identification of differentially-expressed miRNAs were conducted with a GEO2R online tool based on R language. TargetScan 6.2 was used to predict the targets of differentially-expressed miRNAs. Protein-protein interaction network analysis was conducted by STRING 9.1, while functional enrichment [Gene Ontology (GO) biological process terms] and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted by GeneCodis3 for the target genes. A total of 6 differentially-expressed miRNAs were screened out, with 317 target genes obtained. It was found that 67 interactions existed among 76 genes/proteins through the PPI network analysis, and that 6 of these were potential key genes (PIK3R5, MAPK3, PTEN, S1PR3, BDKRB2 and NCBP2). The main biological processes involved in chemoresistant ovarian carcinoma were apoptosis, programmed cell death, cell migration, cell death and cell motility. The miRNA target genes were found to be associated with the ErbB signaling pathway, the gonadotropin-releasing hormone signaling pathway and other pathways in cancer. IK3R5, MAPK3 and PIK3R5 are involved in the majority of GO terms and KEGG pathways associated with chemoresistance in ovarian carcinoma. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to evaluate the frequency and absolute number of circulating innate lymphoid cell (ILC) subsets and their associations with clinical and serological features in systemic lupus erythematosus (SLE). Patients and methods: We recruited 28 SLE patients (6 males, 22 females; mean age 37.57 years; range, 18 to 56 years) and 13 healthy controls (4 males, 9 females; mean age 32.08 years; range, 19 to 48 years). Circulating ILC subsets were identified by flow cytometry. Associations between all detected cells and SLE disease activity, clinical manifestations, and serum autoantibodies were analyzed. Results: In this study, significantly higher frequencies of ILC2s and ILC3s, lower frequencies of ILC1s, and higher ILC1/ILC3 and ILC1/ILC2 ratios were observed in SLE patients than in healthy controls. The frequencies and number of ILC3s were positively associated with SLE disease activity index 2000 score and anti-double stranded deoxyribonucleic acid titers in patients with SLE. Decreased ILC1 frequencies, increased ILC3 frequencies, and decreased ILC1/ILC3 and ILC2/ILC3 ratios were observed in patients with arthritis compared to those without arthritis. Conclusion: Our results indicated biased altered distributions of circulating ILC subsets in SLE. ILC3s were associated with SLE disease activity, and ILC1s, ILC3s, and ILC1/ILC3 and ILC2/ILC3 ratios were associated with SLE accompanied with arthritis. Taken together, these results suggest that ILCs may serve as cellular biomarkers for disease activity and arthritis involvement in SLE. [ABSTRACT FROM AUTHOR]

Biomarkers of temporomandibular joint (TMJ) osteoarthritis (OA) remain unknown. The objective was to detect whether molecular biomarkers from peripheral blood leucocytes (PBLs) engage in TMJ OA lesions. Thirty‐four six‐week‐old Sprague Dawley rats were used. The top upregulated gene ontology categories and gene‐fold changes in PBLs were detected by a microarray analysis comparing rats that received 20‐week unilateral anterior crossbite (UAC) treatment with age‐matched controls (n = 4). Twenty weeks of UAC treatment had been reported to induce TMJ OA‐like lesions. The other twenty‐four rats were randomly placed in the UAC and control groups at 12‐ and 20‐week time points (n = 6). The mRNA expression levels of the selected biomarkers derived from the microarray analysis and their protein expression in the alveolar bone and TMJ were detected. The microarray analysis indicated that the three most highly involved genes in PBLs were Egr1, Ephx1 and Il10, which were confirmed by real‐time PCR detection. The increased protein expression levels of the three detected molecules were demonstrated in cartilage and subchondral bone (P < 0.05), and increased levels of EPHX1 were reported in discs (P < 0.05); however, increased levels were not present in the alveolar bone. Immunohistochemistry revealed the increased distribution of EGR1‐positive, EXPH1‐positive and IL10‐positive cells predominantly in the osteochondral interface, with EXPH1 also present in TMJ discs. In conclusion, the increased mRNA expression of Egr1, Ephx1 and Il10 in PBLs may serve as potential biomarkers for developed osteoarthritic lesions relating to osteochondral interface hardness changes induced by dental biomechanical stimulation. [ABSTRACT FROM AUTHOR]

Abstract: Epitestosterone (ET) has been used as a masking agent and prohibited by the World Anti-Doping Agency (WADA) because its administration will decrease the urinary T/ET ratio, a marker of testosterone (T) administration. In this study, an off-line immunoaffinity extraction coupled with high performance liquid chromatography (HPLC) was developed to quantify the endogenous steroid ET in human urine. The immunoaffinity column (IAC) was prepared by immobilizing the anti-ET monoclonal antibodies on CNBr-activated Sepharose 4B, which can remove the contaminations and non-target compounds from matrix to enrich the target analyte ET. The mobile phase was ammonium acetate (10mM, pH 4.0)/acetonitrile (45/55, v/v) at an isocratic flow of 1.0mL/min and the UV absorbance detection wavelength was 244nm for the detection of ET. The IAC showed good reliability and durability since it had been used for more than 100 runs in a year. The limit of quantification (LOQ) was 1ng/mL. Satisfied repeatability and precision of the day-to-day and within-day were obtained with the RSD values less than 10%. Results of the recovery of the urine samples were ranged from 98% to 102% with repeatability less than 9%, indicating that the method developed can be used for the real urine sample analysis. [Copyright &y& Elsevier]

Fifteen compounds were obtained from Polygonatum prattii Baker, which could be divided into four steroids, nine flavonoids, one lignanoid and one acidamide. The chemotaxonomic significance of P. prattii and the some other species among Asparagaceae was also discussed. As a result, Polygonatum may have close relationships with Liriope , Disporopsis , Ophiopogon and Aspidistra. Additionally, homoisoflavanones and steroids can be recognized as typical biomarkers for the above genus. • Fifteen compounds are isolated from P. prattii. • Compounds 1 – 11 and 13 – 15 were obtained from P. prattii for the first time. • Polygonatum may have close relationships with four genus of Asparagaceae. [ABSTRACT FROM AUTHOR]

• Twenty-week aberrant occlusion caused rat masseter atrophy. • Twenty-week aberrant occlusion did not cause atrophy in rat lateral pterygoid muscle. • Twenty-week aberrant occlusion upregulated Fbxo32 expression in rat masseter. • Twenty-week aberrant occlusion did not change Fbxo32 in rat lateral pterygoid muscle. • Increased Fbxo32 expression would be a candidate biomarker of rat masseter atrophy. To detect the long-term response to unilateral anterior crossbite (UAC) in masticatory muscles and in molecular biomarkers of peripheral blood leukocytes. Fifty-six six-week-old Sprague-Dawley rats were used. The gene-fold changes in peripheral blood leukocytes were detected by the microarray analysis to compare the rats that received 20-week UAC treatment with age-matched controls (n = 4). Muscle atrophy-related gene Fbxo32 was selected based on the data of the microarray analysis verified by using real-time PCR. The remaining 36 rats were randomly separated in the UAC and control groups at 12 and 20 weeks (n = 12). The protein expression of Fbxo32 and the muscle injury and myogenesis-related markers, αB-crystallin and desmin, were detected in the masseter and lateral pterygoid muscles by western blot assay. In the 20-week UAC group, the masseter muscle weight was lower than that in the age-matched control group, and the expression level of Fbxo32 gene in peripheral blood leukocytes was increased according to the microarray analysis confirmed by real-time PCR detection. The increased protein expression levels of Fbxo32 were detected in the masseter in the 20-week UAC group, and the protein expression levels of desmin and αB-crystallin were decreased at this time point. No similar changes were detected in the lateral pterygoid muscle. Masseter atrophy is induced by long-term stimulation of UAC. The increased expression of the Fbxo32 gene in peripheral blood leukocytes may be a candidate biological marker of masseter atrophy. [ABSTRACT FROM AUTHOR]