Expression of Duffy antigen receptor for chemokines (DARC) is down-regulated in colorectal cancer

Abstract

Duffy antigen receptor for chemokines (DARC) is a silent chemokine receptor which selectively binds angiogenic chemokines without inducing conventional signaling responses. DARC has been reported to inhibit the development of multiple cancers through clearance of angiogenic chemokines. However, its role in colorectal cancer (CRC) remains unclear. We investigated the expression of DARC in CRC and explored correlation of DARC expression with clinical pathological features and microvessel density (MVD). The protein expression levels of DARC were detected by immunohistochemistry in 90 CRC and 64 paired unaffected tissues. The mRNA levels of DARC were detected by quantitative real-time PCR in 15 CRC and paired unaffected tissues. MVD in CRC was also assessed by immunohistochemistry of CD34. We found that the mRNA and protein expression levels of DARC were significantly lower in CRC than in the unaffected tissues (p?<?0.05). The DARC protein expression levels were positively correlated with DARC mRNA expression levels in both CRC (p?<?0.001) and unaffected tissues (p?<?0.001). We also found that DARC expression was significantly correlated with tumor differentiation (p?<?0.001), lymph node metastasis (p?<?0.01) and TNM stage (p?<?0.05). Moreover, we observed a strong negative relationship between DARC expression and MVD in CRC (p?<?0.001). We showed that DARC expression is down-regulated in CRC and associated with clinical pathological features and MVD of CRC. DARC might be involved in tumorigenesis, progression, angiogenesis, and metastasis of CRC.     

The methylation status of TNF-α and SOCS3 promoters and the regulation of these gene expressions in patients with Behçet’s disease

Abstract

Introduction: The aim of this study was to evaluate the methylation status of TNF-α and SOCS3 promoters in patients with BD and compare them with a healthy group.

Method: This was a case–control study, in which 47 subjects with BD and 61 individuals as the control participated. Blood samples were collected from all the participants. Then, PBMCs were isolated using the Ficoll method and methylation of considered sites was investigated using the qMS-PCR technique after DNA extraction by the rapid genomic DNA extraction method and its analysis with Nano-drop.

Results: The methylation and expression of TNF-α showed that the methylation level significantly declined in the patient in comparison with the healthy (p?<?0.05). Moreover, the results on the mean expression showed that it significantly increased in the patient group, as compared with the healthy group (p?<?0.05). In addition, the expression of the SOCS3 gene was not significantly different between the patients and healthy subjects while the level of SOCS3 methylation was significantly higher in the patient group than that in the healthy group (p?<?0.05).

Discussion: The present study revealed that the gene expression of TNF-alpha increased in BD patients, suggesting that TNF-alpha likely has a role in the pathogenesis of BD.     

The association between micronucleus,nucleoplasmic bridges,and nuclear buds frequency and the degree of uterine cervical lesions

Background and aim: The loss of genomic stability plays an important role in carcinogenesis. Therefore, it is imperative to use certain biomarkers of DNA damage due to genomic instability in order to predict cancer risk. The aim of this study was the evaluation of genomic instability in patients with cervical lesions.

Materials and methods: We investigated the genetic damages in 80 subjects: 40 patients with high-grade squamous intraepithelial lesions (HSIL), 20 patients with invasive squamous cervical cancer (SCC) and 20 healthy women with a biomarker in two different tissues; the micronucleus (MN) test in peripheral blood lymphocytes (PBL), and in buccal exfoliated cells (BEC). This study also examined the frequency of other nuclear anomalies such as nucleoplasmic bridges (NPBs) and nuclear bunds (NBUDs) in PBL.

Results: The frequency of MN in BEC, MN in PBL, NPB in PBL and NBUD in PBL were significantly higher (p?Conclusion: Although larger studies are needed, our data support the predictive value of MN, NPB and NBUD as biomarkers of genomic instability for evaluation of risk level of cancer diseases.     

Potential signal pathway of all-trans retinoic acid for MMP-2 and MMP-9 expression in injury podocyte induced by adriamycin

Abstract

All-trans-retinoic acid (ATRA) can regulate some specific genes expression in various tissue and cells via nuclear retinoic acid receptors (RARs), including three subtypes: retinoic acid receptor-alpha (RAR-α), retinoic acid receptor-beta (RAR-β) and retinoic acid receptor-gamma (RAR-γ). Podocyte injury plays a pivotal role in the progression of glomerulosclerosis (GS). This study was performed to study the potential signal pathway of ATRA in the expression of matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9) in injury podocyte. Cells were divided into three groups: group of negative control (NC), group of injury podocyte induced by adriamycin (ADR) (AI) and group of ADR inducing podocyte injury model treated with ATRA (AA). The cells morphology changes were detected using microscope and scanning electron microscopy. MMP-2 and MMP-9 enzymic activity was detected using the gelatin zymography method. Protein and mRNA expressions of MMP-2, MMP-9, RAR-α, RAR-β and RAR-γ were measured by western-blot and real-time RT-PCR. Enzymatic activity of MMP-2 and MMP-9 in group AA was significantly enhanced compared to AI group after ATRA-treated 24?h (p?<?0.05). The protein and mRNA expressions of MMP-2/MMP-9 in group AA were significantly increased than those in group AI at both 12 and 24?h time points (p?<?0.05). Compared to group AI, RAR-α and RAR-γ protein/mRNA expressions of group AA were significantly increased at both 12 and 24?h time points (p?<?0.05). There was no difference for the expression of RAR-β between group AI and group AA (p?>?0.05). RAR-α protein level was positively correlated with MMP-2 or MMP-9 protein expression (p?<?0.05), and RAR-γ protein level was also positively correlated with MMP-2 or MMP-9 protein expression (p?<?0.05). In conclusion, ATRA may increase expression of MMP-2 and MMP-9 by the potential signal pathway of RAR-α and RAR-γ in injury podocyte induced by adriamycin, but not RAR-β.     

Association between red blood cell distribution width and long-term mortality among patients undergoing percutaneous coronary intervention with previous history of cancer

Abstract

Background: The number of patients suffering from coronary heart disease with cancer is rising. There is scarce evidence concerning the biomarkers related to prognosis among patients undergoing percutaneous coronary intervention (PCI) with cancer. Thus, the aim of this study was to investigate the association between red blood cell distribution width (RDW) and prognosis in this population.

Methods: A total of 172 patients undergoing PCI with previous history of cancer were enrolled in this retrospective study. The endpoint was long-term all-cause mortality. According to tertiles of RDW, the patients were classified into three groups: Tertile 1 (RDW <12.8%), Tertile 2 (RDW ≥12.8% and <13.5%) and Tertile 3 (RDW ≥13.5%).

Results: During an average follow-up period of 33.3 months, 29 deaths occurred. Compared with Tertile 3, mortality of Tertile 1 and Tertile 2 was significantly lower in the Kaplan–Meier analysis. In multivariate Cox regression analysis, RDW remained an independent risk factor of mortality (HR: 1.938, 95% CI: 1.295–2.655, p?<?0.001). The all-cause mortality in Tertile 3 was significantly higher than that in Tertile 1 (HR: 5.766; 95% CI: 1.426–23.310, p?=?0.014).

Conclusions: An elevated RDW level (≥13.5%) was associated with long-term all-cause mortality among patients undergoing PCI with previous history of cancer.     

Prognostic value of pre-treatment red blood cell distribution width in lung cancer: a meta-analysis

Abstract

Objective: In recent years, increasing studies found that pre-treatment red blood cell distribution width (RDW) could predict clinical outcomes in various cancers. However, the prognostic value of pre-treatment RDW in lung cancer was inconsistent. Therefore, we performed a meta-analysis to determine prognostic value of pre-treatment RDW in lung cancer.

Methods: We performed a search in PubMed, The Cochrane Library, EMBASE (via OVID), Web of Science, CNKI, Wanfang, VIP, SinoMed databases, then we identified all records up to February 15, 2019. Outcomes of interest were overall survival (OS) and disease-free survival (DFS). Hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs) were calculated to assess the relevance of pre-treatment RDW to OS in lung cancer.

Results: We included ten articles in total. Pooled results revealed that elevated pre-treatment RDW was significantly associated with poor OS (HR?=?1.55, 95% CI: 1.26–1.92, p?<?0.001) and DFS (HR?=?1.53, 95% Cl: 1.15–2.05; p?=?0.004) in lung cancer. Further subgroup analysis manifested that lung cancer patients with elevated pre-treatment RDW had worse prognosis.

Conclusions: A higher value of pre-treatment RDW indicated worse survival of patients with lung cancer. RDW may serve as a reliable and economical marker for prediction of lung cancer prognosis.     

JTC-801 exerts anti-proliferative effects in human osteosarcoma cells by inducing apoptosis

Background: The research of G protein-coupled receptors (GPCRs) is a promising strategy for drug discovery. In cancer therapy, there is a need to discover novel agents that can inhibit proliferation and induce apoptosis in cancer cells. JTC-801 is a novel GPCR antagonist with the function of reversing pain and anxiety symptoms. This study aims to investigate the antitumor effects of JTC-801 on human osteosarcoma cells (U2OS) and elucidate the underlying mechanism.

Materials and methods: The Cell Counting Kit-8 assay was used to detect the viability of U2OS cells treated with JTC-801 in vitro. The cell apoptosis was evaluated using a flow cytometry assay with Annexin V-FITC/PI double staining. The inhibitory effect of JTC-801 on invasion and migration of U2OS cells were determined by the Transwell assays. Western blot assay was performed to measure the levels of proteins related to cell apoptosis and its mechanism.

Results: The JTC-801 significantly decreased the viability of U2OS cells (p?p?p?Conclusions: JTC-801 may exert osteosarcoma cell growth inhibition by promoting cell apoptosis, through PI3K/AKT signaling pathway participation.     

Urinary cell cycle arrest biomarker [TIMP-2]·[IGFBP7] in patients with hepatorenal syndrome

Abstract

Background: Patients with hepatorenal syndrome carry a high short-term mortality. Early diagnosis and treatment are essential for patients’ outcome. Nevertheless diagnosis of HRS remains difficult. First-line therapy terlipressin is often associated with severe complications. Biomarkers become more on focus for an early diagnosis.

Objective: The aim of this study was to test the diagnostic accuracy of urinary [TIMP-2]·[IGFBP7] for HRS patients and prognostic value for therapy responding patients.

Material and methods: NephroCheck^® measures urinary concentrations of TIMP-2 and IGFBP-7, both indicating stress of renal cells and associated with induction of cell cycle arrest. 22 HRS patients and 30 patients with normal kidney function were included. [TIMP-2]·[IGFBP7] was measured using NephroCheck^®. HRS patients receiving terlipressin were also examined.

Results: [TIMP-2]·[IGFBP7] values did not differ significantly (1.3?±?2.09 vs. 1.03?±?1.03; p?=?0.55). Furthermore, there was no significant difference of [TIMP-2]·[IGFBP7] regarding response of terlipressin (1.32?±?2.39 vs. 0.81?±?1.05; p?=?0.56). Low [TIMP-2]·[IGFBP7] values were significantly associated with higher mortality (p?=?0.01).

Conclusions: The results of this study suggest that [TIMP-2]·[IGFBP7] is not suitable for diagnostic of HRS and prediction of therapy response, but there might be evidence for prognostic value of [TIMP-2]·[IGFBP7] in regard to mortality of liver cirrhosis patients.     

Differentially expressed miR-20, miR-21, miR-100, miR-125a and miR-146a as a potential biomarker for prostate cancer

Prostate cancer is the leading cause of death among men worldwide. Deregulation of microRNAs has been reported in many cancers. Expression of microRNAs miR-20a-5p, miR-21-5p, miR-100-5p, miR-125a-5p and miR-146a-5p in tissue blocks of histologically confirmed prostate cancer patients compared with BPH patients, to identify potential microRNA biomarker for prostate cancer. MicroRNA was isolated and expression was quantified by qRT-PCR using Taqman Advanced microRNA assay kits. The interactions between the microRNA:target mRNA were predicted by using bioinformatics tools such as miRwalk and miRTargetlink. The experimentally validated targets were analysed using gprofiler to identify their molecular function, biological process and related pathways. The expression analysis revealed that miR-21 and miR-100 were significantly down-regulated whereas miR-125a was up-regulated in prostate cancer patients. Comparative analysis of the expression levels with tumor grading reveal that miR-100 was significantly down-regulated (p?<?0.05) in high grade tumor, indicating that miR-100 associated with prostate cancer. ROC analysis revealed that combined analysis of down-regulated miRNAs (miR-21 and miR-100) shown AUC of 0.72 (95% CI 0.65–0.79). The combined analysis of all five miRNAs showed AUC of 0.87 (95% CI 0.81–0.92). The targets prediction analysis revealed several validated targets including BCL2, ROCK1, EGFR, PTEN, MTOR, NAIF1 and VEGFA. Our results provide evidence that combined analysis of all the five miRNAs as a panel can significantly improve the prediction level of the presence of prostate cancer and may be used as a potential diagnostic biomarker.

     

Association between circulating irisin levels and epicardial fat in patients with treatment-naïve overt hyperthyroidism

Abstract

Background: Hyperthyroidism is associated with increased metabolic activity and thermogenesis. Irisin is a key molecule in thermogenesis and energy expenditure via adipose tissue browning. Epicardial fat was previously defined as brown-like fat. Thus, here we aimed to evaluate the association between serum irisin level and epicardial fat thickness (EFT) in patients with hyperthyroidism.

Methods: A total of 25 hyperthyroid patients and 24 age-, sex- and BMI-matched healthy controls were enrolled. Serum irisin levels, thyroid hormone levels, and body compositions were compared. EFT was measured via transthoracic echocardiography.

Results: Serum irisin level and EFT were significantly higher in the hyperthyroid group (p?<?0.001 and p?=?0.001, respectively). The distributions of fat-free mass, muscle mass and fat mass were similar between the study groups. Serum irisin level was negatively correlated with TSH (p?<?0.001) and positively correlated with fT3 (p?<?0.001), fT4 (p?<?0.001) and TSH receptor antibody (p?=?0.002) levels and EFT (p?=?0.001). In multivariate linear regression analysis, TSH (β?=??0.475, p?<?0.001) and EFT (β?=?0.290, p?=?0.023) levels were significantly associated with serum irisin levels.

Conclusions: An increased serum irisin level associated with EFT might contribute to metabolic derangement in hyperthyroidism. Further studies are needed to elucidate whether irisin levels and EFT are affected by hyperthyroidism or vice versa.     

Evaluation of mediators of oxidative stress and inflammation in patients with acute appendicitis

Context: This study aims to explore the potential of new inflammatory markers for improving the challenging diagnosis of acute appendicitis (AA).

Methods: Levels of IL-1, IL-6, IL-8, IL-10, CRP, INF-γ, and TNF-α in serum were measured in 73 patients with AA. Oxidative stress and antioxidant enzymes were analyzed.

Results: Serum levels of interleukins, TNF-α, and INF-γ were significantly elevated in patients with appendicitis (p?<?0.0001), except for IL-10, which presented decreased levels. There were no significant differences in SOD (p?=?0.29), CAT (p?=?0.19), or TBARS levels (p?=?0.18), whereas protein carbonyls presented significant increase (p?<?0.0001).

Conclusion: Evaluating these biomarkers could aid in diagnosing AA.     

Loss of FBXW7 is related to the susceptibility and poor prognosis of cervical squamous carcinoma

Objective: To investigate the relationship between F box/WD-40 domain protein 7 (FBXW7) and cervical squamous cancer.

Methods: We investigated the FBXW7 expression in 136 cervical squamous carcinoma cases through immunohistochemistry and Western-blot analysis to evaluate the clinical significance of FBXW7 and to elucidate the relationship of FBXW7 expression with progression-free survival (PFS) and overall survival (OS).

Results: Low FBXW7 expression was associated with high histologic grade, lymphovascular space invasion and lymph node metastasis, among other parameters. Patients with low FBXW7 expression exhibited poor OS and PFS.

Conclusions: FBXW7 is related to the susceptibility and prognosis of cervical squamous carcinoma, indicating FBXW7 may be a potentially important target for the prediction of prognosis.     

Recurrence prediction using microRNA expression in hormone receptor positive breast cancer during tamoxifen treatment

Abstract

Purpose: To identify miRNAs associated with distant recurrence during tamoxifen treatment and build a recurrence prediction model.

Materials and methods: We measured the expression of five miRNAs (miR-134, miR-125b-5P, miRNA-30a, miR-10a-5p and miR-222). A total of 176 tumour tissues from 176 patients who had hormone receptor positive breast cancer with tamoxifen treatment were used to measure miRNA expression using quantitative real-time PCR (qRT-PCR).

Results: The five miRNAs were all up-regulated in distant recurrence cases within 5?years after surgery and during tamoxifen treatment. Kaplan-Meier survival analyses based on expression cut-offs determined by receiver characteristics curves (ROC) showed that high expression of miR-134, miR-125b-5P, miRNA-30a, miR-10a-5p and miR-222 were significantly (log-rank p-value =0.006, p-value <0.0001, p-value <0.0001, p-value <0.0001 and p-value <0.0001, respectively) associated with short relapse-free time. Our results were used to build a combined 3 miRNAs expression model. It could be used to categorize high-risk subset of patients with short relapse-free survival (AUC =0.891, p-value <0.0001).

Conclusions: Distant recurrence during tamoxifen treatment of hormone positive breast cancer might be affected by tamoxifen resistance related miRNAs. Such distant recurrence can be predicted using miRNA measurement.     

Comparative study of observed actions,motor imagery and control therapeutic exercise on the conditioned pain modulation in the cervical spine: a randomized controlled trial

Abstract

Aim: The aim of this study was to compare the effects of cervical exercise, motor imagery (MI) and action observation (AO) of cervical exercise actions on conditioned pain modulation and pressure pain thresholds. The second objective was to assess the effects of these interventions on cervical motor activity (ranges of motion and muscle endurance), attention, and the ability to generate motor images.

Study design: Single-blinded randomized controlled trial.

Materials and methods: Fifty-four healthy subjects were randomly assigned to each group. Response conditioned pain modulation, pressure pain threshold, were the main variables. The secondary outcome measures included, cervical range of motion, Neck flexor endurance test, mental movement representation associated and psychosocial variables.

Results: All groups showed significant differences in time factor for all evaluated variables (p?<?.01) except pressure pain threshold over the tibial region. The post hoc analysis revealed significant within-group differences in the AE and AO groups in conditioned pain modulation (p?<?.05), with medium effect size in time [AE (d –0.61); AO (d –0.74)].

Conclusion: The results showed that within-group changes in conditioned pain modulation, cervical muscle endurance, and attention where founded only in the AE and AO groups. Variations in pain thresholds at pressure in the trapezium area were also obtained in the three groups. Changes in the ranges of flexion-extension and rotation movement were presented exclusively in the exercise group, and in the capacity to generate motor images only in the AO group. However, there was no difference in the pressure pain threshold over the tibial region.     

Longitudinal analysis of tear cathepsin S activity levels in male non-obese diabetic mice suggests its potential as an early stage biomarker of Sjögren’s Syndrome

Context: Cathepsin S (CTSS) activity is elevated in Sjögren’s Syndrome (SS) patient tears.

Objective: To evaluate longitudinal expression of tear and tissue CTSS activity relative to other disease indicators in Non-Obese Diabetic (NOD) mice.

Methods: CTSS activity was measured in tears and lacrimal glands (LG) from male 1–6?month (M) NOD and 1 and 6?M BALB/c mice. Lymphocytic infiltration was quantified by histopathology, while disease-related proteins (Rab3D, CTSS, collagen 1) were quantified using q-PCR and immunofluorescence.

Results: In NOD LG, lymphocytic infiltration was noted by 2?M and established by 3?M (p?<?0.01). IFN-?, TNF-α, and MHC II expression were increased by 2?M (p?<?0.01). Tear CTSS activity was significantly elevated at 2?M (p?<?0.001) to a maximum of 10.1-fold by 6?M (p?<?0.001). CTSS activity in LG lysates was significantly elevated by 2?M (p?<?0.001) to a maximum of 14-fold by 3?M (p?<?0.001). CTSS and Rab3D immunofluorescence were significantly increased and decreased maximally in LG acini by 3?M and 2?M, respectively. Comparable changes were not detected between 1 and 6?M BALB/c mouse LG, although Collagen 1 was decreased by 6?M in LG of both strains.

Conclusion: Tear CTSS activity is elevated with other early disease indicators, suggesting potential as an early stage biomarker for SS.     

Dynamic thiol/disulphide homeostasis as indicator of oxidative stress in automotive workers

Abstract

Purpose: To examine thiol-disulphide homeostasis auto painters.

Materials and methods: A total of 115 male workers, including 60 auto painters workers and 55 reference group, of the painting and assembly line units respectively, were included in the study. Thiol-disulphide parameters and ischaemia-modified albumin (IMA) of groups were determined. Urinary hippuric acid, (HA) phenol, hexanedione, trichloroacetic acid, arsenic and blood lead and manganese were analysed.

Results: The median urinary HA level was significantly higher in auto painters when compared to the reference group [(2461 (1212) vs. 520 (513) µgr/L), (p?<?0.001)] . The mean disulphide level [19.7 (4.3) vs 0.15.1(4.1) μmol/L, (p?<?0.001)], the disulphide/native thiol ratio [4.72 (1.47) vs. 3.13 (1.21, (p?<?0.001)] and the disulphide/total thiol ratio [4.31 (1.23) vs. 2.94 (1.06), (p?<?0.001)] were higher in auto painters when compared to the reference group. There was a statistically significant positive correlation between urinary HA and disulphide concentrations (r?=?0.536 and p?<?0.001), disulphide/native thiol ratio (r?=?0.564 and p?<?0.001) and the disulphide/total thiol ratio (r?=?0.564 and p?<?0.001) and IMA (r?=?0.396 and p?<?0.001).

Conclusion: The results presented in this study showed that oxidative stress can be associated with occupational exposure to toluene denoted by alteration of thiol disulphide homeostasis and ischaemia-modified albumin levels.     

Plasma sE-cadherin and the plasma sE-cadherin/sVE-cadherin ratio are potential biomarkers for chronic obstructive pulmonary disease

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation with endothelial dysfunction. Cadherins are adhesion molecules on epithelial (E-) and vascular endothelial (VE-) cells. Soluble (s) cadherin is released from the cell surface by the effects of proteases including matrix metalloproteinases (MMPs).

Objective: The aim of this study was to examine the associations of sE-/sVE-cadherin levels in plasma with the development of COPD.

Methods: Plasma sE-/VE-cadherin levels were measured by an enzyme-linked immunosorbent assay in 115 patients with COPD, 36 symptomatic smokers (SS), 63 healthy smokers (HS) and 78 healthy non-smokers (HN). sE-cadherin and MMP-7 levels in epithelial lining fluid (ELF) were measured in 24 patients (12 COPD and 12 control).

Results: Plasma sE-cadherin levels and sE-cadherin/sVE-cadherin ratios were significantly higher in COPD and SS than in HS and HN groups, while plasma sVE-cadherin levels were lower in COPD than in HS and HN groups (p?p?p?p?Conclusions: Plasma sE-cadherin levels and sE-cadherin/sVE-cadherin ratios are potential biomarkers for COPD.