Comparison of growth factor levels in injectable platelet-rich fibrin obtained from healthy individuals and patients with chronic periodontitis: a pilot study.

BACKGROUND: This study aimed to assess and compare the concentrations of growth factors, white blood cells (WBCs), and platelets in injectable platelet-rich fibrin (i-PRF) derived from people with healthy periodontal conditions and those with chronic periodontitis. METHODS: Venous blood samples were obtained from 30 patients diagnosed with chronic periodontitis (test group) and 30 participants with healthy periodontal conditions (control group). The i-PRF was then acquired from centrifuged blood. The growth factors (VEGF, IGF-1, TGF-ß1, PDGF-BB and EGF) released from the i-PRF samples were compared between groups with ELISA testing. The amounts of WBCs and platelets were also compared. RESULTS: No significant differences in the concentrations of growth factors were found between the groups (the mean values for the control and test groups were, respectively: IGF: 38.82, 42.46; PDGF: 414.25, 466.28; VEGF: 375.69, 412.18; TGF-ß1: 21.50, 26.21; EGF: 138.62, 154.82). The test group exhibited a significantly higher WBC count than the control group (8.80 vs. 6.60, respectively). However, the platelet count did not show a statistically significant difference between the groups (control group 242.0 vs. test group 262.50). No significant correlation was observed between WBC count and growth factor level in either group. CONCLUSIONS: The growth factor levels in i-PRFs did not exhibit significant difference between the two groups. This suggests that the levels of these growth factors may be unaffected by the periodontal disease.

Bystander LECT2 amyloidosis in tumor nephrectomy.

Pathologic evaluation of the non-neoplastic renal parenchyma in tumor nephrectomy specimens is critical and can detect both renal-limited and systemic pathologies. We report the case of a 69-year-old Punjabi male who underwent cytoreductive nephrectomy for advanced renal cell carcinoma after immunotherapy. We detected clinically unexpected leukocyte chemotactic factor 2 (LECT2) amyloidosis during pathologic analysis of the surrounding non-neoplastic renal parenchyma, which was confirmed by mass spectrometry. LECT2 amyloidosis occurs predominantly in Hispanic patients and has only rarely been described in Punjabi patients. This case highlights the importance of careful pathologic evaluation of the non-neoplastic renal parenchyma of nephrectomy specimens and raises awareness that LECT2 amyloidosis can occur outside of the typical demographic of Hispanic patients.

Prognostic value of Dickkopf-1 and ß-catenin expression according to the antitumor immunity of CD8-positive tumor-infiltrating lymphocytes in biliary tract cancer.

The role of ß-catenin and Dickkopf-1 (DKK1) is dependent on the specific immunobiology of T cell inflammation in biliary tract cancer (BTC). We aimed to analyze the role of DKK1 or ß-catenin as a prognostic factor in BTC, and determine the clinical associations of ß-catenin and DKK1 with CD8+ tumor-infiltrating lymphocytes (TIL). We used data from The Cancer Genome Atlas Research Network and the clinicopathological data of 145 patients with BTC who had undergone primary radical resection between 2006 and 2016. CD8+ TIL expression was a significant predictor of favorable overall survival (OS) and relapse-free survival (RFS) (median OS, 34.9 months in high-TIL, 16.7 months in low-TIL, P < 0.0001 respectively; median RFS, 27.1 months in high-TIL, 10.0 months in low-TIL, P < 0.0001 respectively). In the high-CD8+ TIL BTC group, the tumor expression of ß-catenin and DKK1 had a significant negative impact on either OS or RFS. In the low-TIL BTC group, there were no differences according to ß-catenin and DKK1 expression. Cox regression multivariate analysis demonstrated that CD8+ TIL and ß-catenin retained significant association with OS. Among patients with resected BTC, the ß-catenin and DKK1 protein and high CD8+ TIL levels were associated with poor and good clinical outcomes, respectively.

The effect of the anticoagulant on the cellular composition and growth factor content of platelet-rich plasma.

BACKGROUND: The cellular and biochemical composition of the platelet rich plasma (PRP) may impact its regenerative capacity. PRP composition have been shown to vary substantially among different separation systems and protocols. The type and the dose of anticoagulant might affect the content of PRP. OBJECTIVE: The objective of this study was to evaluate the effect of anticoagulant use, on cellular composition and the amount of growth factors in fresh PRP. METHODS: Three different methods were used to prepare PRP from 12 healthy participants. The protocol 1 included standart dose sodium citrate (SC) (0.9 ml, 3.8%), protocol 2 included 0.5 ml SC and no anticoagulant was used in protocol 3. The PRP's were compared in regards to cellular content, capture efficiency of platelets (CE), concentrations and total doses of fresh studied vascular endothelial growth factor (VEGF), platelet derived growth factor -BB, (PDGF-BB), transforming growth factor ß1 (TGF-ß1) levels. RESULTS: The CE and total platelet count were highest in protocol 1. The white blood cells (WBC) and VEGF were highest in protocol 3. The highest total TGF-ß1 and total PDGF levels were obtained with protocol 1, while the highest total VEGF levels were obtained with protocol 3. CONCLUSION: The results of this study revealed that the use and the dose of SC affects the cellular content of PRP and GFs measured in fresh PRP. The CE and platelet dose increases while the WBC and VEGF decreases with the use of SC.

Mesothelial-to-Mesenchymal Transition and Exosomes in Peritoneal Metastasis of Ovarian Cancer.

Most patients with ovarian cancer (OvCA) present peritoneal disseminated disease at the time of diagnosis. During peritoneal metastasis, cancer cells detach from the primary tumor and disseminate through the intraperitoneal fluid. The peritoneal mesothelial cell (PMC) monolayer that lines the abdominal cavity is the first barrier encountered by OvCA cells. Subsequent progression of tumors through the peritoneum leads to the accumulation into the peritoneal stroma of a sizeable population of carcinoma-associated fibroblasts (CAFs), which is mainly originated from a mesothelial-to-mesenchymal transition (MMT) process. A common characteristic of OvCA patients is the intraperitoneal accumulation of ascitic fluid, which is composed of cytokines, chemokines, growth factors, miRNAs, and proteins contained in exosomes, as well as tumor and mesothelial suspended cells, among other components that vary in proportion between patients. Exosomes are small extracellular vesicles that have been shown to mediate peritoneal metastasis by educating a pre-metastatic niche, promoting the accumulation of CAFs via MMT, and inducing tumor growth and chemoresistance. This review summarizes and discusses the pivotal role of exosomes and MMT as mediators of OvCA peritoneal colonization and as emerging diagnostic and therapeutic targets.

The Growth Factors and Cytokines of Dental Pulp Mesenchymal Stem Cell Secretome May Potentially Aid in Oral Cancer Proliferation.

BACKGROUND: Growth factors and cytokines responsible for the regenerative potential of the dental pulp mesenchymal stem cell secretome (DPMSC-S) are implicated in oral carcinogenesis. The impact and effects of these secretory factors on cancer cells must be understood in order to ensure their safe application in cancer patients. OBJECTIVE: We aimed to quantify the growth factors and cytokines in DPMSC-S and assess their effect on oral cancer cell proliferation. MATERIALS AND METHODS: DPMSCs were isolated from patients with healthy teeth (n = 5) that were indicated for extraction for orthodontic reasons. The cells were characterized using flow cytometry and conditioned medium (DPMSC-CM) was prepared. DPMSC-CM was subjected to a bead-based array to quantify the growth factors and cytokines that may affect oral carcinogenesis. The effect of DPMSC-CM (20%, 50%, 100%) on the proliferation of oral cancer cells (AW123516) was evaluated using a Ki-67-based assay at 48 h. AW13516 cultured in the standard growth medium acted as the control. RESULTS: VEGF, HCF, Ang-2, TGF-α, EPO, SCF, FGF, and PDGF-BB were the growth factors with the highest levels in the DPMSC-CM. The highest measured pro-inflammatory cytokine was TNF-α, followed by CXCL8. The most prevalent anti-inflammatory cytokine in the DPMSC-CM was IL-10, followed by TGF-ß1 and IL-4. Concentrations of 50% and 100% DPMSC-CM inhibited Ki-67 expression in AW13516, although the effect was non-significant. Moreover, 20% DPMSC-CM significantly increased Ki-67 expression compared to the control. CONCLUSIONS: The increased Ki-67 expression of oral cancer cells in response to 20% DPMSC-CM indicates the potential for cancer progression. Further research is needed to identify their effects on other carcinogenic properties, including apoptosis, stemness, migration, invasion, adhesion, and therapeutic resistance.

Expression of the axon guidance factor Slit2 and its receptor Robo1 in patients with Hirschsprung disease: An observational study.

ABSTRACT: Hirschsprung disease (HD) is a common form of digestive tract malformation in children. However, the pathogenesis of HD is not very clear. This study aimed to investigate the expression of slit guidance ligand 2 (Slit2) and roundabout 1 (Robo1) in patients with HD.From January 2018 to January 2019, 30 colon specimens from children with HD undergoing surgical resection at the Department of Surgery in Qilu Children's Hospital of Shandong University were obtained. These specimens were divided into the normal segment group, the transitional segment group and the spastic segment group. Immunohistochemical staining, Western blotting, and real-time polymerase chain reaction were used to measure the expression of Slit2 and Robo1 in the intestinal walls of normal, transitional, and spastic segments.Immunohistochemical staining and Western blot analyses showed high levels of the Slit2 and Robo1 proteins in normal ganglion cells in children with HD, lower levels in transitional ganglion cells, and no expression in spastic segments, with significant differences between groups (P < .05). Similarly, the real-time polymerase chain reaction results were consistent with the Western blot analysis results.The expression of Slit2 and Robo1 decreases significantly in the spastic segment of the intestinal tract in patients with HD.

Adropin levels and its associations as a fat-burning hormone in patients with polycystic ovary syndrome: a correlational meta-analysis.

AIMS: Adropin is a peptide hormone with potential implications in patients with polycystic ovary syndrome (PCOS). The aim of this meta-analysis was to compare the circulating (serum/plasma) and follicular fluid adropin levels between human PCOS patients and non-PCOS controls. METHODS: Relevant studies were retrieved by online database and manual searching. The standardized mean differences (SMDs) with 95% confidence intervals (CIs) were obtained by a random-effects meta-analysis. Meta-analysis of correlations was performed for the associations of adropin with anthropometric, lipid, insulin resistance and hormonal covariates. The funnel plot analysis with Begg's and Egger's tests was used for publication bias. RESULTS: A total of 9 studies were included in this meta-analysis. The results indicated that the adropin levels were significantly decreased in PCOS patients as compared to non-PCOS controls (SMD = -1.87, 95% CI = -2.55 to -1.18, p < .0001). This decrease was more evident in overweight PCOS patients than their normoweight counterparts (SMD = -0.55, 95% CI = -0.80 to -0.30, p < .0001). A one-study leave-out sensitivity analysis indicated that no single study had a significant influence on the overall outcome, suggesting the robustness of this meta-analysis. There were significant associations of decreased adropin levels with the body mass index, dyslipidemia and insulin resistance in PCOS. CONCLUSION: Adropin levels are significantly reduced in PCOS patients compared to controls, and this decrease was more evident in overweight PCOS patients.

Validation of a DKK1 RNAscope chromogenic in situ hybridization assay for gastric and gastroesophageal junction adenocarcinoma tumors.

Dickkopf-1 (DKK1) is a secreted modulator of Wnt signaling that is frequently overexpressed in tumors and associated with poor clinical outcomes. DKN-01 is a humanized monoclonal therapeutic antibody that binds DKK1 with high affinity and has demonstrated clinical activity in gastric/gastroesophageal junction (G/GEJ) patients with elevated tumoral expression of DKK1. Here we report on the validation of a DKK1 RNAscope chromogenic in situ hybridization assay to assess DKK1 expression in G/GEJ tumor tissue. To reduce pathologist time, potential pathologist variability from manual scoring and support pathologist decision making, a digital image analysis algorithm that identifies tumor cells and quantifies the DKK1 signal was developed. Following CLIA guidelines the DKK1 RNAscope chromogenic in situ hybridization assay and digital image analysis algorithm were successfully validated for sensitivity, specificity, accuracy, and precision. The DKK1 RNAscope assay in conjunction with the digital image analysis solution is acceptable for prospective screening of G/GEJ adenocarcinoma patients. The work described here will further advance the companion diagnostic development of our DKK1 RNAscope assay and could generally be used as a guide for the validation of RNAscope assays with digital image quantification.

Frequency and type of adverse analytical findings in athletics: Differences among disciplines.

Athletics is a highly diverse sport that contains a set of disciplines grouped into jumps, throws, races of varying distances, and combined events. From a physiological standpoint, the physical capabilities linked to success are quite different among disciplines, with varying involvements of muscle strength, muscle power, and endurance. Thus, the use of banned substances in athletics might be dictated by physical dimensions of each discipline. Thus, the aim of this investigation was to analyse the number and distribution of adverse analytical findings per drug class in athletic disciplines. The data included in this investigation were gathered from the Anti-Doping Testing Figure Report made available by the World Anti-Doping Agency (from 2016 to 2018). Interestingly, there were no differences in the frequency of adverse findings (overall,~0.95%, range from 0.77 to 1.70%) among disciplines despite long distance runners having the highest number of samples analysed per year (~9812 samples/year). Sprinters and throwers presented abnormally high proportions of adverse analytical findings within the group of anabolic agents (p < 0.01); middle- and long-distance runners presented atypically high proportions of findings related to peptide hormones and growth factors (p < 0.01); racewalkers presented atypically high proportions of banned diuretics and masking agents (p = 0.05). These results suggest that the proportion of athletes that are using banned substances is similar among the different disciplines of athletics. However, there are substantial differences in the class of drugs more commonly used in each discipline. This information can be used to effectively enhance anti-doping testing protocols in athletics.

Improves symptoms and urinary biomarkers in refractory interstitial cystitis/bladder pain syndrome patients randomized to extracorporeal shock wave therapy versus placebo.

Extracorporeal shock wave therapy (ESWT) has been shown to improve symptoms in patients with interstitial cystitis/bladder pain syndrome (IC/BPS); however, there is a lack of objective evidence. We measured change of urinary biomarker levels in 25 patients with IC/BPS received ESWT or placebo once a week for 4 weeks. Urines were collected from participants at baseline, 4 and 12 weeks post treatment. A representative 41 inflammatory growth factors, cytokines, and chemokines in urine were measured using a MILLIPLEX immunoassay kit. Symptom bother was assessed by O'Leary-Sant symptom scores (OSS), and visual analog scale (VAS) for pain. The ESWT group exhibited a significant reduction in the OSS and VAS compared to the placebo group 4 weeks post-treatment (P < 0.05), and the effects were persistent at 12 weeks. The difference in urinary markers change in ESWT versus placebo was P = 0.054 for IL4, P = 0.013 for VEGF, and P = 0.039 for IL9 at 4 weeks. The change of urine biomarker was not significant in other biomarkers or all the measured proteins at 12 weeks. The current data suggest that IL4, IL9, and VEGF mediation may be involved in its pathophysiologic mechanisms and response to LESW treatment.

Anti-inflammatory effect of different PRGF formulations on cutaneous surface.

Cutaneous autoimmune and inflammatory diseases are a major burden of global disease and many lack effective treatments that can derive in different dermatoses like atopic dermatitis. Despite the increase prevalence and the high health-care costs worldwide, the heterogeniety and multifactoriality of these diseases mean that effective treatment options are scarce. Plasma rich in growth factors (PRGF) technology could be an alternative approach that may help in the management of this cutaneous condition. The aim of this study was to assess the effect of two different PRGF formulations (just activated and autologous topical serum (ATS)) for the management of skin inflammation. Additionally, ATS was assessed over two patients suffering from radiotherapy induced dermatitis. Human organotypic skin explant cultures (hOSECs) were used as human skin models. To induce atopic dermatitis-like conditions, skin explants were treated with both interleukin-4 (IL-4) and interleukin-13 (IL-13). PRGF and ATS were intradermally and topically applied, respectively. Metabolic activity, reactive oxigen species (ROS), necrosis and inflammatory cytokine production were determined. Both PRGF formulations increased tissue viability and significantly reduced the excessive free radical accumulation and the cutaneous cytokine production such as TNF-α and IL-1ß. Case reports showed a positive response after ATS treatment in terms of skin quality improvement, local erythema decrease and burning and itching amelioration. The oedema, swelling and desquamation caused by radiation induced dermatitis was also reduced and the patients referred ceased pruritus and pain. This preliminary study suggests that PRGF might aid in the management of inflammatory skin conditions.

Potential Effects of Nonadherent on Adherent Human Umbilical Venous Endothelial Cells in Cell Culture.

The adherence and shear-resistance of human umbilical venous endothelial cells (HUVEC) on polymers is determined in vitro in order to qualify cardiovascular implant materials. In these tests, variable fractions of HUVEC do not adhere to the material but remain suspended in the culture medium. Nonadherent HUVEC usually stop growing, rapidly lose their viability and can release mediators able to influence the growth and function of the adherent HUVEC. The aim of this study was the investigation of the time dependent behaviour of HUVEC under controlled nonadherent conditions, in order to gain insights into potential influences of these cells on their surrounding environment in particular adherent HUVEC in the context of in vitro biofunctionality assessment of cardiovascular implant materials. Data from adherent or nonadherent HUVEC growing on polystyrene-based cell adhesive tissue culture plates (TCP) or nonadhesive low attachment plates (LAP) allow to calculate the number of mediators released into the culture medium either from adherent or nonadherent cells. Thus, the source of the inflammatory mediators can be identified. For nonadherent HUVEC, a time-dependent aggregation without further proliferation was observed. The rate of apoptotic/dead HUVEC progressively increased over 90% within two days. Concomitant with distinct blebbing and loss of membrane integrity over time, augmented releases of prostacyclin (PGI2, up to 2.91 ± 0.62 fg/cell) and platelet-derived growth factor BB (PDGF-BB, up to 1.46 ± 0.42 fg/cell) were detected. The study revealed that nonadherent, dying HUVEC released mediators, which can influence the surrounding microenvironment and thereby the results of in vitro biofunctionality assessment of cardiovascular implant materials. Neglecting nonadherent HUVEC bears the risk for under- or overestimation of the materials endothelialization potential, which could lead to the loss of relevant candidates or to uncertainty with regard to their suitability for cardiac applications. One approach to minimize the influence from nonadherent endothelial cells could be their removal shortly after observing initial cell adhesion. However, this would require an individual adaptation of the study design, depending on the properties of the biomaterial used.

Model establishment of prognostic-related immune genes in laryngeal squamous cell carcinoma.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors of the head and neck in the world. At present, the treatment methods include surgery, radiotherapy, and chemotherapy, but the 5-year survival rate is still not ideal and the quality of life of the patients is low. Due to the relative lack of immunotherapy methods, this study aims to build a risk prediction model of related immune genes, which can be used to effectively predict the prognosis of laryngeal cancer patients, and provide targets for subsequent immunotherapy. METHODS: We collected the 111 cases of laryngeal squamous cell carcinoma and 12 matched normal samples in the The Cancer Genome Atlas Database (TCGA) gene expression quantification database. The differentially expressed related immune genes were screened by R software version 3.5.2. The COX regression model of immune related genes was constructed, and the sensitivity and specificity of the model were evaluated. The risk value was calculated according to the model, and the risk curve was drawn to verify the correlation between related immune genes, risk score, and clinical traits. RESULTS: We selected 8 immune-related genes that can predict the prognosis of LSCC in a COX regression model and plotted the Kaplan-Meier survival curve. The 5-year survival rate of the high-risk group was 16.5% (95% CI: 0.059-0.459), and that of the low-risk group was 72.9% (95% CI: 0.555-0.956). The area under the receiver operating characteristic (ROC) curve was used to confirm the accuracy of the model (AUG = 0.887). After univariate and multivariate regression analysis, the risk score can be used as an independent risk factor for predicting prognosis. The risk score (P = .021) was positively correlated with the clinical Stage classification. CONCLUSION: We screened out 8 immune genes related to prognosis: RBP1, TLR2, AQP9, BTC, EPO, STC2, ZAP70, and PLCG1 to construct risk value models, which can be used to speculate the prognosis of the disease and provide new targets for future immunotherapy.

Aspirin Rescues Wnt-Driven Stem-like Phenotype in Human Intestinal Organoids and Increases the Wnt Antagonist Dickkopf-1.

BACKGROUND & AIMS: Aspirin reduces colorectal cancer (CRC) incidence and mortality. Understanding the biology responsible for this protective effect is key to developing biomarker-led approaches for rational clinical use. Wnt signaling drives CRC development from initiation to progression through regulation of epithelial-mesenchymal transition (EMT) and cancer stem cell populations. Here, we investigated whether aspirin can rescue these proinvasive phenotypes associated with CRC progression in Wnt-driven human and mouse intestinal organoids. METHODS: We evaluated aspirin-mediated effects on phenotype and stem cell markers in intestinal organoids derived from mouse (ApcMin/+ and Apcflox/flox) and human familial adenomatous polyposis patients. CRC cell lines (HCT116 and Colo205) were used to study effects on motility, invasion, Wnt signaling, and EMT. RESULTS: Aspirin rescues the Wnt-driven cystic organoid phenotype by promoting budding in mouse and human Apc deficient organoids, which is paralleled by decreased stem cell marker expression. Aspirin-mediated Wnt inhibition in ApcMin/+ mice is associated with EMT inhibition and decreased cell migration, invasion, and motility in CRC cell lines. Chemical Wnt activation induces EMT and stem-like alterations in CRC cells, which are rescued by aspirin. Aspirin increases expression of the Wnt antagonist Dickkopf-1 in CRC cells and organoids derived from familial adenomatous polyposis patients, which contributes to EMT and cancer stem cell inhibition. CONCLUSIONS: We provide evidence of phenotypic biomarkers of response to aspirin with an increased epithelial and reduced stem-like state mediated by an increase in Dickkopf-1. This highlights a novel mechanism of aspirin-mediated Wnt inhibition and potential phenotypic and molecular biomarkers for trials.

Reduced MFAP5 expression in stroma of gallbladder adenocarcinoma and its potential diagnostic utility.

The diagnosis of invasive adenocarcinoma of the gallbladder can sometimes be challenging. The presence of true desmoplastic reaction facilitates the diagnosis of invasion. However, desmoplasia-like changes can be observed in benign gallbladder conditions, and recognition of desmoplasia may be challenging based on morphology. In this study, we tested the expression pattern of microfibril-associated protein 5 (MFAP5), a promising immunohistochemical marker for desmoplasia, in benign gallbladders with desmoplasia-like reaction and gallbladders with invasive adenocarcinoma. We also evaluated the diagnostic utility of MFAP5 in challenging cases with an interobserver agreement study. The results showed that all benign cases retained intact/positive MFAP5 staining pattern in periglandular connective tissue, whereas 79.3% (23 out of 29) of cases of adenocarcinomas demonstrated diffuse and complete loss of MFAP5 staining in the tumor stroma. Interobserver agreement was improved by 2.66 times when images of MFAP5 immunohistochemistry were provided. In conclusion, MFAP5 expression is downregulated in the desmoplastic stroma of gallbladder adenocarcinoma and may provide a useful diagnostic marker in difficult cases.

The relationship between hepatoma-derived growth factor and prognosis in non-small cell lung cancer: A systematic review and meta-analysis.

BACKGROUND: Hepatoma-derived growth factor (HDGF) promotes cancer progression and metastasis by interacting with vascular endothelial growth factor, thereby inducing epithelial-to-mesenchymal transition and angiogenesis. Recent studies have correlated increased HDGF levels with poor prognosis in various malignancies, including lung cancer. This meta-analysis systematically assessed the prognostic significance of HDGF expression in patients with non-small cell lung cancer (NSCLC). METHODS: Eligible studies were identified by searching literature in PubMed, Embase, Scopus, and the Cochrane library until June 2020. The pooled hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) was determined to assess the relationship between HDGF expression and clinical outcome in patients with NSCLC. RESULTS: The pooled HRs between high HDGF expression and clinical outcome were 2.20 (95% CI 1.75-2.76, P < .001) and 2.77 (95% CI 1.79-4.29, P < .001) for overall survival and disease-free survival, respectively. High HDGF expression was significantly correlated with a larger tumor size (OR 1.59, 95% CI 1.02-2.46, P = .040). CONCLUSION: HDGF expression is related to clinical outcome and may be a prognostic marker in patients with NSCLC.

Molecular differences between arterial and venous grafts in the first year after coronary artery bypass grafting.

Despite commonly used for coronary artery bypass surgery, saphenous vein (SV) grafts have significantly lower patency rates in comparison to internal thoracic artery (ITA) grafts, which might be due to the structural characteristics of the vessel wall but also due to differences in oxidative stress adaptation and molecular signaling and regulation. This human post mortem study included a total of 150 human bypass grafts (75 SV grafts and 75 ITA grafts) obtained from 60 patients divided into five groups due to the time period of implantation: group 1: baseline group without grafting; group 2: 1 day; group 3: > 1 day-1 week; group 4: > 1 week-1 month; group 5: > 1 month-1 year. Pieces of 3 mm length were fixed with formaldehyde, dehydrated, wax embedded, cut into sections of 3 µm thickness, and histologically and immunohistochemically examined. Over the whole time period, we observed a lower neointima formation and a better preserved media in ITA grafts with a higher percentage of TNF-α, PDGFR-α, and VEGF-A in nearly all vessel wall layers, a higher amount of MMP-7, MMP-9, EGFR, and bFGF positive cells in SV grafts and a timely different peak not only between ITA and SV grafts but also within the various vessel wall layers of both graft types. Since most of the examined growth factors, growth factor receptors and cytokines are regulated by MAPKs, our results suggest an activation of different pathways in both vessel graft types immediately after bypass grafting.

1H, 13C, and 15N backbone assignments of the C-terminal region of the human retinoic acid-induced protein 2.

Retinoic acid-induced protein 2 is a human protein of 530 residues encoded by the RAI2 gene (Q9Y5P3; RAI2_HUMAN). RAI2 is a novel tumor suppressor protein whose depletion in breast cancer cell lines results in the downregulation of several genes associated with differentiation along with increased invasiveness and aggressive tumor phenotype of the cells. The role of the protein is specified to be a transcriptional regulator that promotes chromosomal stability and hence controls the expression of several regulators of cancer and metastasis. Structurally, RAI2 remains an unknown entity and, hence, to obtain a detailed view on the structure function relationship we report the 1H, 13C, and 15N resonance assignments for the backbone and side chain nuclei of the C-terminal region (a.a. 303-451 of UniProt Q9Y5P3) of RAI2.

Prognostic role of dickkopf-1 in patients with cancer.

As an antagonist for the WNT signal passway, dickkopf-1(DKK1) have a great important role in the occurence and development of various type cancer. The present paper performed a meta-analysis to evaluate the predictive significance of DKK1 in cancer.To assess the relationship between the expression of DKK1 and prognostic role in human cancers, a total of 16 articals were screened from the multiple online databases (Pubmed, EMBASE, CNKI, Web of Science and Google Scholar) in our study. By using the STATA soft,pooled hazard ratio and 95% confidence intervals of overall survival (OS), progression-free survival, disease-free survival and time to recurrence were used to evaluate the strength of this relationship.The meta-analysis showed that higher expression of DKK1 was significantly associated with shorter OS in cancer patients. In stratified analyzes, the higher expression of DKK1 could reduced the OS in patients with breast cancer,digestive system cancer and urogenital system cancer, but not patients with the lung cancer. It also showed that higher expression of DKK1 was significantly associated with shorter progression-free survival, disease-free survival and time to recurrence in cancer patients.The present study indicate that higher expression of DKK1 predict an unfavorable clinical outcome in patients with breast cancer, digestive system cancer and urogenital system cancer.