Circular RNA circEGFR regulates tumor progression via the miR-106a-5p/DDX5 axis in colorectal cancer

Recently, an increasing number of studies have reported that dysregulation of circular RNA (circRNA) expression plays critical roles in the progression of several cancers, including colorectal cancer (CRC). However, the detailed molecular mechanisms of circRNAs involvement in CRC remain largely unknown. Here, we confirmed that the level of circEGFR was significantly increased in CRC tissues compared to matched adjacent non-tumor tissues, and a high level of circEGFR was correlated with poor clinicopathological characteristics and poor prognosis in patients with CRC. Moreover, increased circEGFR expression promoted CRC cell proliferation, migration, and invasion in vitro. Mechanistically, circEGFR acted as a ceRNA for miR-106a-5p to relieve the repressive effect of miR-106a-5p on DDX5 mRNA. Moreover, circEGFR enhanced DDX5 expression, thereby upregulating p-AKT levels. Together, these findings showed that circEGFR promoted CRC cell proliferation, migration, and invasion through the miR-106a-5p/DDX5/AKT axis, and may serve as a promising diagnostic marker and therapeutic target for CRC patients.     

miR-199a-3p targets ETNK1 to promote invasion and migration in gastric cancer cells and is associated with poor prognosis

PurposeTo investigate the prognostic significance of miR-199a-3p and its role in invasion and metastasis in gastric cancer.MethodsmiR-199a-3p expression in 436 formalin-fixed and 39 frozen gastric cancer tissues was investigated by in situ hybridization and RT-PCR, respectively. The role of miR-199a-3p in the migration and invasion of gastric cancer cells was determined in overexpression and inhibitor studies using transwell assays and the SGC-7901, BGC-823 and MGC-803 gastric cancer cells lines. The effect of miR-199a-3p expression on ethanolamine kinase 1 (ETNK1) levels was determined by western botting.ResultsmiR-199a-3p was significantly up-regulated in AGS, SGC-7901, BGC-823 and MGC-803 gastric cancer cells, when compared with GES-1 non-malignant gastric epithelial cells. In situ hybridization studies revealed that human non-tumor gastric mucosa samples were negative for miR-199a-3p expression, while 162 of 436 (37.16%) cases of gastric cancer demonstrated positive expression. miR-199a-3p overexpression was associated with tumor size, Lauren classification, depth of invasion, lymph node and distant metastasis, TNM stage and prognosis. In patients with I, II and III stage tumors, high miR-199a-3p expression was associated with a significantly lower 5-year survival rate. miR-199a-3p overexpression was associated with increased cell migration and invasion. ETNK1 expression was inhibited following miR-199a-3p overexpression in BGC-823 and SGC-7901 cells, and elevated following miR-199a-3p suppression in MGC-803 cells.ConclusionmiR-199a-3p is highly expressed in gastric cancer, and correlates with invasion, metastasis and prognosis. miR-199a-3p regulates the invasion and migration of gastric cancer cells by targeting ETNK1. Consequently, miR-199a-3p may serve as a prognostic indicator in gastric cancer.     

Suppressive effect of platycodin D on bladder cancer through microRNA-129-5p-mediated PABPC1/PI3K/AKT axis inactivation

Platycodin D (PD) is a major constituent of Platycodon grandiflorum and has multiple functions in disease control. This study focused on the function of PD in bladder cancer cell behaviors and the molecules involved. First, we administered PD to the bladder cancer cell lines T24 and 5637 and the human uroepithelial cell line SV-HUC-1. Cell viability and growth were evaluated using MTT, EdU, and colony formation assays, and cell apoptosis was determined using Hoechst 33342 staining and flow cytometry. The microRNAs (miRNAs) showing differential expression in cells before and after PD treatment were screened. Moreover, we altered the expression of miR-129-5p and PABPC1 to identify their functions in bladder cancer progression. We found that PD specifically inhibited the proliferation and promoted the apoptosis of bladder cancer cells; miR-129-5p was found to be partially responsible for the cancer-inhibiting properties of PD. PABPC1, a direct target of miR-129-5p, was abundantly expressed in T24 and 5637 cell lines and promoted cell proliferation and suppressed cell apoptosis. In addition, PABPC1 promoted the phosphorylation of PI3K and AKT in bladder cancer cells. Altogether, PD had a concentration-dependent suppressive effect on bladder cancer cell growth and was involved in the upregulation of miR-129-5p and the subsequent inhibition of PABPC1 and inactivation of PI3K/AKT signaling.     

Overexpression of Arginase-1 is an indicator of poor prognosis in patients with colorectal cancer

AimArginase-1 (Arg-1) metabolizes l-arginine to l-ornithine and urea. It has been documented to have a role in various malignancies. However, the relationship between Arg-1 expression and clinicopathological characteristics of colorectal cancer (CRC) patients remains to be elucidated. The present study aimed to analyze the expression and prognostic value of Arg-1 in patients with CRC.Material and methodsThe mRNA and protein expressions of Arg-1 in fresh colorectal cancer tissue specimens and the corresponding noncancerous tissue specimens were examined by RT-qPCR (n = 24) and western blot analysis (n = 17). Arg-1 expression levels were determined in paraffin-embedded CRC tissue specimens (n = 236) by immunohistochemistry. The associations of Arg-1 expression and clinicopathological features and clinical prognosis in 236 CRC patients were analyzed.ResultsThe expression levels of Arg-1 were significantly higher in the CRC tissues compared with the matched noncancerous tissues, and elevated Arg-1 expression was remarkably associated with stage III-IV tumors (P = 0.007), lymph node metastasis (P = 0.019) and a plasma albumin concentration <35 g/l (P = 0.022). Kaplan-Meier analysis indicated that Arg-1 overexpression was associated with adverse prognoses for overall survival (OS) (P < 0.001) and disease-free survival (DFS) (P < 0.001) in all cases. Further analysis revealed that the patients with high Arg-1 expression had significantly shorter OS and DFS at the advanced stages (III + IV) (P = 0.032 for OS, and P = 0.012 for DFS) but not at the early stages (I + II) (P = 0.194 for OS, and P = 0.065 for DFS). Multivariate analysis revealed that Arg-1 overexpression was an independent prognostic factor for OS (P = 0.002) and DFS (P < 0.001) in patients with CRC.ConclusionThe data indicated that Arg-1 overexpression in CRC may be a marker that can discriminate subgroups of patients with a poor prognosis.     

miR-146a-5p regulates autophagy and NLRP3 inflammasome activation in epithelial barrier damage in the in vitro cell model of ulcerative colitis through the RNF8/Notch1/mTORC1 pathway

Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon that can be influenced by microRNAs (miRNAs). This study aims to investigate the impact of miR-146a-5p on lipopolysaccharide (LPS)-induced Caco-2/HT-29 cell autophagy and NLRP3 inflammasome activation and the underlying mechanism, with the aim of identifying potential therapeutic targets. We used LPS to establish Caco-2/HT-29 cell models and measured cell viability by CCK-8. The levels of miR-146a-5p, RNF8, markers of NLRP3 inflammasome activation and autophagy, proteins involved in the Notch1/mTORC1 pathway, and inflammatory factors were assessed by RT-qPCR, Western blot, and ELISA. Intestinal epithelial barrier function was evaluated by measuring transepithelial electrical resistance. Autophagic flux was measured using tandem fluorescent-labeled LC3. miR-146a-5p was highly-expressed in LPS-induced Caco-2/HT-29 cells, and autophagy flux was blocked at the autolysosomal stage after LPS induction. Inhibition of miR-146a-5p suppressed NLRP3 inflammasome activation, reduced intestinal epithelial barrier damage, and facilitated autophagy inhibition in LPS-induced Caco-2/HT-29 cells. The autophagy inhibitor NH4Cl partially nullified the inhibitory effects of miR-146a-5p inhibition on NLRP3 inflammation activation. miR-146a-5p targeted RNF8, and silencing RNF8 partly abrogated the action of miR-146a-5p inhibition on promoting autophagy and inhibiting NLRP3 inflammasome activation. miR-146a-5p inhibition suppressed the Notch1/mTORC1 pathway activation by upregulating RNF8. Inhibition of the Notch1/mTORC1 pathway partially nullified the function of silencing RNF8 on inhibiting autophagy and bolstering NLRP3 inflammasome activation. In conclusion, miR-146a-5p inhibition may be a potential therapeutic approach for UC, as it facilitates autophagy of LPS-stimulated Caco-2/HT-29 cells, inhibits NLRP3 inflammasome activation, and reduces intestinal epithelial barrier damage by upregulating RNF8 and suppressing the Notch1/mTORC1 pathway.     

Unique profiles of targetable genomic alterations and prognosis in young Chinese patients with lung adenocarcinoma

ObjectiveLung adenocarcinoma in young patients is a rare entity, and the targetable genomic alterations (GAs) are poorly studied. In other cancers, it has been demonstrated that young age defines unique disease biology. Here, the association of young age with GAs and prognosis is studied in a large cohort of Chinese patients.MethodsWe retrospectively screened 1000 consecutive patients, and identified 181 patients aged 40 years or younger. GAs were identified by next-generation sequencing (NGS) assay. The clinical and genetic characteristics were analyzed.ResultsAmong younger group, 167(92.3%) patients were diagnosed withadvanced-stage adenocarcinoma, 98(54.1%) were female, 27(14.9%) were smokers, and the median age was 35 years. Targetable GAs which were significantly more common in the younger population (P < 0.001), were associated with young age (P < 0.05). The frequency of ALK translocations, EGFR and KRAS mutations was 37.6%, 34.3% and 6.1%, respectively. Younger patients had a higher prevalence of rare GAs including HER2, ROS1 and MET (P < 0.05). Prognosis for younger patients was similar (median OS of patients with GAs, 23.91 vs 23.67 months, P > 0.05) or better than that for older population (median OS of patients without GAs, 44.28 vs 41.88 months, P < 0.05) according to GAs. Therapy modality was an independent prognostic factor (P < 0.05), and 83% of death rate decreased if given preferred therapy.ConclusionYounger patients with lung adenocarcinoma had unique prevalence of targetable GAs. Comprehensive genotyping including NGS is recommended for personalized therapy and prognosis evaluation in this population.     

Expression and clinical significance of FOS-like antigen 1 in gastric adenocarcinoma

BackgroundThe overexpression of FOS-like antigen 1 (FOSL1) in several types of cancers was reported before. However, the expression and clinical significance of FOSL1 in gastric cancer (GC) have not been elucidated.Materials and methodsThe expression of FOSL1 in 105 cases of GCs was detected with immunohistochemistry, and the mRNA of FOSL1 was investigated with quantitative real-time polymerase chain reaction(qRT-PCR) in 15 pairs of GCs and tumor adjacent tissues. With Chi-square test or Fisher test, we analyzed the correlation between FOSL1 expression and clinicopathological factors. With univariate analysis, we evaluated the correlations between clinicopathological factors including FOSL1 and overall survival (OS) rates. With multivariate analysis, we identified the independent prognostic risk factors of GC.ResultsThe percentages of patients with low and high FOSL1 expression in our study accounted for 43.81% and 56.19%, respectively. The mRNA levels of FOSL1 in GCs were significantly higher than those in tumor adjacent tissues. FOSL1 expression was demonstrated to be significantly correlated with lymphatic invasion (P = 0.036) and TNM stage (P = 0.016). High expression of FOSL1 was significantly correlated with lower 5-year OS (P = 0.002), and FOSL1 expression was identified as an independent prognostic biomarker of GC (P = 0.001).ConclusionsFOSL1 is an independent prognostic biomarker of GC. Detecting FOSL1 expression could help stratify GC patients with high-risk and guide the precious treatment.     

Decreased expression levels of DAL-1 and TOB1 are associated with clinicopathological features and poor prognosis in gastric cancer

PurposeWe previously demonstrated that the functional inactivation of DAL-1 and TOB1 promotes an aggressive phenotype in gastric cancer cells, but the links between both genes and the survival of patients with gastric cancer are unknown. Here, we investigated the correlations of the expression levels of DAL-1 and TOB1 with the progression of gastric cancer.MethodsA total of 270 patients who underwent resectable gastrectomy were included. The expression of DAL-1 and TOB1 was detected by immunohistochemistry.ResultsLow expression of DAL-1 in cancer tissue was significantly associated with tumor site (p < 0.05), histological grade (p < 0.01), depth of invasion (p < 0.05), lymph node metastasis status (p < 0.05), Lauren classification (p < 0.001), and clinical stage (p < 0.01). A lower level of TOB1 was observed in gastric cancer patients with diffuse type disease compared to patients with either intestinal or mixed type disease (p < 0.001). Additionally, Spearman’s correlation analysis revealed that decreased expression of DAL-1 was positively correlated with low TOB1 expression (r=0.304, p < 0.001). The survival analysis showed that low levels of DAL-1 and TOB1 were significantly associated with poor survival of gastric cancer patients (p <0.001 and p < 0.05, respectively).ConclusionThe downregulation of DAL-1 and TOB1 expression is associated with shorter survival of gastric cancer patients. Hence, DAL-1 and TOB1 may be considered potential novel markers for predicting the outcomes of patients with gastric cancer.     

miR-455-5p suppresses hepatocellular carcinoma cell growth and invasion via IGF-1R/AKT/GLUT1 pathway by targeting IGF-1R

Hepatocellular carcinoma (HCC) is among the most frequently observed forms of cancer. MicroRNAs (miRNAs) are increasingly thought to play a key role in regulating the onset and progression of a wide range of cancer types. In the present report, we found that miR-455-5p expression was significantly decreased in both HCC patient tumor tissues and cell lines, and that this reduction in expression was linked to poorer patient outcomes. When we overexpressed miR-455-5p in HCC cell lines (Huh7 and HepG2), this was linked with impaired proliferation, colony formation, migration, and invasion. We further found that this miRNA was able to directly bind the insulin growth factor receptor (IGF-1R) 3′-untranslated region, thereby suppressing IGF-1R expression in HCC cells. Consistent with this, miR-455-5p overexpression was associated with reduced glucose transporter (GLUT) 1 expression, which in turn inhibited HCC cell uptake of glucose, production of lactate, and generation of ATP. Together these results thus indicate that mIR-455-5p is able to suppress tumor functionality via impairing glycolysis in HCC cells, highlighting this miRNA as a potential target for anti-cancer therapeutic interventions.     

Serum TEM5 and TEM7 concentrations correlate with clinicopathologic features and poor prognosis of colorectal cancer patients

PurposeColorectal cancer (CRC) is a serious threat worldwide; therefore, discovering sensitive and specific serum biomarkers for early stages of CRC is a great challenge. In this study, we evaluated whether tumour endothelial marker 5 (TEM5) and 7 (TEM7) circulating in blood serum can be useful as blood-based markers for detection, progression, and prognosis in CRC patients. Moreover, their specificity and sensitivity in the early diagnosis of CRC were compared with common carcinoma diagnostic markers, i.e. CEA and Ca 19-9.Materials and methodsThe study included 45 CRC patients and 35 healthy individuals. The serum concentration of TEM5 and TEM7 were quantified using sandwich ELISA.ResultsThe mean TEM5 and TEM7 serum concentrations were statistically significantly higher in the CRC patients than in the healthy controls. Moreover, the mean TEM5 and TEM7 concentrations were statistically significantly higher in the serum of patients with late stage (III/IV) compared to early stage (I/II) cancer. The TEM5 and TEM7 values increased along the development of the T, N, and M stages. The TEM5 and TEM7 sensitivity and specificity in CRC detection were higher than routinely used blood markers (CEA, Ca19-9). The high TEM5 and TEM7 concentrations were associated with worse overall survival compared to CRC patients of low TEM5 and TEM7 concentrations.ConclusionsTaken together, these findings suggest that TEM5 and TEM7 serum concentrations can be considered as useful biomarkers for the detection of CRC patients and for monitoring cancer progression and identifying patients with a high possibility of poor survival.     

MiR-188-5p and MiR-141-3p influence prognosis of bladder cancer and promote bladder cancer synergistically

MicroRNA (miRNA) plays a significant role in suppressing the occurrence and development of tumor by inhibiting the translation of target proteins. Although previous researches have verified many miRNAs’ functions in bladder cancer (BC), the function of miR-188-5p and miR-141-3p in BC still remains unknown. Our experiment manifested that miR-188-5p and miR-141-3p were highly expressed in BC tissues and cells, which indicated a poor prognosis. In vitro functional assays suggested that down-regulated miR-188-5p and miR-141-3p inhibited the proliferation, migration and invasion of BC cells, while a combination of half dose down-regulated miR-188-5p and half dose down-regulated miR-141-3p demonstrated a more obvious inhibition effect. All results indicated that miR-188-5p and miR-141-3p promoted BC respectively and synergistically. Therefore, miR-188-5p and miR-141-3p will not only assist the diagnosis of BC, but also serve as more effective joint markers to predict the progression of BC.     

Prognostic value of long non-coding RNA FOXD2-AS1 expression in patients with solid tumors

BackgroundAlthough increasing evidence has revealed that FOXD2-AS1 overexpression exists in various solid tumors, the value of FOXD2-AS1 as a prognostic marker in such cancers remains uncertain. Accordingly, the present research aimed to assess the association of FOXD2-AS1 with cancer prognosis and predict the biological function of FOXD2-AS1.MethodsWe systematically retrieved PubMed, PMC, Web of Science, EMBASE and Wiley Online Library databases for eligible articles published up to December 2018. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to evaluate the correlation of FOXD2-AS1 expression with overall survival (OS), disease free survival (DFS) and clinicopathological characteristics. We also used five Gene Expression Omnibus (GEO) datasets from breast cancer patients to explore the relationship between FOXD2-AS1 expression and prognosis. Finally, we validated FOXD2-AS1 expression in various carcinomas and predicted its biological function based on the public databases.ResultsA total of 13 studies with 2502 tumor patients were included. The pooled HRs demonstrated that FOXD2-AS1 overexpression was significantly associated with unfavorable OS (HR = 1.39, 95%CI: 1.23–1.57, p < 0.001) and DFS (HR = 2.24, 95%CI: 1.55–3.23, p < 0.001) in tumor patients. The pooled ORs indicated that FOXD2-AS1 upregulation was related to large tumor size (OR = 1.53, 95%CI: 1.26–1.85, p < 0.001), deep invasion depth (OR = 1.99, 95%CI: 1.53–2.58, p < 0.001), distant metastasis (OR = 2.03, 95%CI: 1.69–2.43, p < 0.001) and advanced TNM stage (OR = 1.35, 95%CI: 1.06–1.72, p = 0.0150), but not to lymph node metastasis nor differentiation. Moreover, a similar pooled result for the OS of breast cancer patients was obtained (HR = 1.55, 95%CI: 1.14–2.11, p = 0.0052) by analyzing GEO data. Finally, elevated FOXD2-AS1 expression in various solid tumor tissues was verified based on The Cancer Genome Atlas (TCGA) data. Further functional prediction demonstrated that FOXD2-AS1 may participate in some cancer-related pathways.ConclusionElevated FOXD2-AS1 expression was associated with poor survival in patients with solid tumors and may serve as a potential prognostic biomarker for a variety of cancers.     

Diagnostic power of VEGF,MMP-9 and TIMP-1 in patients with breast cancer. A multivariate statistical analysis with ROC curve

PurposeVascular endothelial growth factor is an important factor in promoting angiogenesis in malignant processes, matrix metalloproteinase-9 in the degradation of extracellular matrix, which enhances metastasis, and tissue inhibitor of metalloproteinase-1 is its inhibitor. The aim of this study was to investigate the diagnostic power of these parameters in comparison to CA15-3 in breast cancer patients and in relation to the control group.Materials/methodsThe study included 120 breast cancer patients, 60 patients with benign breast tumors and 60 healthy women. Plasma levels of tested parameters were determined by enzyme-linked immunosorbent assay, CA15-3 by chemiluminescent microparticle immuno assay.ResultsTissue inhibitor of metalloproteinase-1 showed the highest value of sensitivity in breast cancer group (86.25%) and, more importantly, highest value in breast cancer stage I (85%). Vascular endothelial growth factor also showed high sensitivity (stage I and II–75%, III–85%, IV–70% and 76.25% in total breast cancer group) and the highest specificity (85%) from all tested parameters. It was also the only parameter which had statistically significant area under curve in all stages. In the total breast cancer group all tested parameters showed statistically significant area under curve, but the maximum range was obtained for combination: ‘vascular endothelial growth factor + CA15-3′. Vascular endothelial growth factor seems to be the best candidate for diagnosing breast cancer stage I and for differentiating between breast cancer and non-carcinoma cases.ConclusionsThe combined analysis of tested parameters and CA15-3 resulted in an increase in sensitivity and area under curve values, which provides hope for developing new panel of biomarkers that may be used in diagnosing breast cancer in the future.     

Evaluation of IgE antibodies to recombinant pollen allergens (Phl p 1, Phl p 2, and Phl p 5) in a random sample of patients with specific IgE to Phleum pratense

BACKGROUND: We measured specific IgE levels against the recombinant allergens (RAs) rPhl p 1, rPhl p 2, and rPhl p 5 in patients allergic to grass pollen, and examined the existence of different patterns of IgE production to RAs. The seasonal variations of IgE levels to rPhl p 1, rPhl p 2, and rPhl p 5 were considered, too. METHODS: Blood was taken from 276 consecutive patients with allergy to grass pollen diagnosed by patient history and skin prick testing. Total and specific serum IgE was measured by the immunoenzymatic CAP FEIA System. Eosinophil cationic protein (ECP) and myeloperoxidase (MPO) were assessed by radioimmunoassay according to the instructions of the manufacturers. RESULTS: We observed eight different patterns of IgE production to rPhl p 1, rPhl p 2, and rPhl p 5 in patients with specific IgE to timothy grass. A significant difference between the values of IgE levels to timothy and the sum of each level of specific IgE to individual RAs was found (P = 0.039, Wilcoxon matched pairs test) in the whole population (n = 276 subjects). In four subgroups of patients, the sum of each level of specific IgE to individual RAs was equal to the levels of specific IgE to timothy grass extract. In one subgroup, the sum of IgE to RAs was lower than the levels of IgE to the natural counterpart (P = 0.013). A lack of subjects in two subgroups did not permit comparison at all. Finally, three subjects with specific IgE to timothy did not show specific IgE to RAs. Out of 276 patients, blood was taken from two different groups of subjects at different time points: November-January and May-July, respectively. The median values were as follows: total IgE = 139 kU/l, IgE to timothy = 10.2 kUA/l; IgE to rPhl p 1 = 3.6 kUA/l, to rPhl p 2 = <0.35 kUA/l, and to rPhl p 5 = 1.1 kUA/l; ECP = 8.25 microg/l; MPO = 303.08 microg/l (before exposure to grass pollen); total IgE = 159 kU/l, IgE to timothy = 57.2 kUA/l; IgE to rPhl p 1 = 22.1 kUA/l, to rPhl p 2 = 5.9 kUA/l, and to rPhl p 5 = 3.9 kUA/l; ECP = 16.21 microg/l; MPO = 413.09 microg/l (during the pollen season). There were significant variations of specific IgE levels between the patients exposed to pollen and the unexposed patients. Moreover, there were statistical differences in the IgE, ECP, and MPO levels in sera before and during the pollen season P<0.035, P<0.017, and P<0.0062, respectively. CONCLUSIONS: The results suggest that RAs allow establishment of the patient's IgE-reactivity profile, encourage future research, and encourage manufacturers to produce further RAs for precise diagnosis and substantially improved immunotherapy injection of only those allergens against which significant amounts of specific IgE are produced.     

Immunohistochemical expression pattern of RIP5, FGFR1, FGFR2 and HIP2 in the normal human kidney development

AimPresent study analyses the co-localisation of RIP5 with FGFR1, FGFR2 and HIP2 in the developing kidney, as RIP5 is a major determinant of urinary tract development, downstream of FGF-signaling.MethodsParaffin embedded human kidney tissues of 16 conceptuses between the 6th-22th developmental week were analysed using double-immunofluorescence method with RIP5/FGFR1/FGFR2 and HIP2 markers. Quantification of positive cells were performed using Kruskal–Wallis test.ResultsIn the 6th week of kidney development RIP5 (89.6%) and HIP2 (39.6%) are strongly expressed in the metanephric mesenchyme. FGFR1 shows moderate/strong expression in the developing nephrons (87.3%) and collecting ducts (70.5%) (p < 0.05). RIP5/FGFR1 co-localized at the marginal zone and the ureteric bud with predominant FGFR1 expression. FGFR2 (26.1%) shows similar expression pattern as FGFR1 (70.5%) in the same kidney structures. RIP5/FGFR2 co-localized at the marginal zone and the collecting ducts (predominant expression of FGFR2). HIP2 is strongly expressed in collecting ducts (96.7%), and co-localized with RIP5. In 10th week, RIP5 expression decrease (74.2%), while the pattern of expression of RIP5 and FGFR1 in collecting ducts (33.4% and 91.9%) and developing nephrons (21.9% and 32.4%) (p < 0.05) is similar to that in the 6th developmental week. Ureter is moderately expressing RIP5 while FGFR1 is strongly expressed in the ureteric wall. FGFR2 is strongly expressed in the collecting ducts (84.3%) and ureter. HIP2 have 81.1% positive cells in the collecting duct. RIP5/FGFR1 co-localize in collecting ducts and Henley’s loop.ConclusionsThe expression pattern of RIP5, FGFR1, FGFR2 and HIP2 in the human kidney development might indicate their important roles in metanephric development and ureteric muscle layer differentiation through FGF signaling pathways.     

GRACE score of myocardial infarction patients correlates with oxidative stress index,hsCRP and inflammation

BackgroundEtiopathogenesis of myocardial infarction (MI) is contributed by oxidative injury and inflammatory response. The interplay of these processes determines outcomes in MI patients. However, studies showing the relationship of oxidative stress and inflammatory cytokines with prognosis and severity of MI are lacking.ObjectiveThe present study was designed to assess the degree of oxidative stress and inflammation in correlation with GRACE (Global Registry of Acute Coronary Events) risk score in patients of MI.MethodsMI patients were segregated according to GRACE risk score and age. Blood samples of the patients were used for determination of level of total peroxide, Total Antioxidant Status (TAS), Oxidative Stress Index (OSI), pro-inflammatory molecules such as high sensitive C-reactive protein (hsCRP), Tumor Necrosis Factor α (TNFα), interleukin 1 β (IL 1β), interleukin 6 (IL 6), anti-inflammatory cytokine interleukin 10 (IL 10), and TNFα/IL 10 cytokine ratio.ResultsWe found significant elevation in concentration of total peroxide, TAS and OSI in all MI patients than healthy volunteers, this elevation showed pronouncement with higher GRACE score (GS) and age. Alteration in pro-inflammatory and anti-inflammatory cytokines was seen in MI patients than control group, and this alteration displayed polarization with GS and age.ConclusionMI patients with higher GS and age have greater degree of OSI and inflammation, and these biochemical parameters were significantly correlated with GS and thus disease severity.