Altered miRNAs Expression Correlates With Gastroenteropancreatic Neuroendocrine Tumors Grades

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and heterogeneous tumors that present a wide spectrum of different clinical and biological characteristics. Currently, tumor grading, determined by Ki-67 staining and mitotic counts, represents the most reliable predictor of prognosis. This time-consuming approach fails to reach high reproducibility standards thus requiring novel approaches to support histological evaluation and prognosis. In this study, starting from a microarray analysis of paraffin-embedded tissue specimens, we defined the miRNAs signature for poorly differentiated NETs (G3) compared to well-differentiated NETs (G1 and G2) consisting of 56 deregulated miRNAs. We identified 8 miRNAs that were expressed in all GEP-NETs grades but at different level. Among these miRNAs, miR-96-5p expression level was progressively higher from grade 1 to grade 3; inversely, its target FoxO1 expression decreased from grade 1 to grade 3. Our results reveal that the miRNAs expression profile of GEP-NET is correlated with the tumor grade, showing a potential advantage of miRNA quantification that could aid clinicians in the classification of common GEP-NETs subtypes. These findings could reliably support the histological evaluation of GEP-NETs paving the way toward personalized treatment approaches

Clinical efficacy of adjunctive methods for the non-surgical treatment of peri-implantitis: a systematic review and meta-analysis

Background: The aim of this systematic review (SR) was to evaluate the clinical efficacy of different adjunctive methods/therapies to the non-surgical treatment (NST) of peri-implantitis. Materials and methods: The protocol of the review was registered in PROSPERO database (CRD42022339709) and was designed according to PRISMA statement. Electronic and hand searches were performed to identify randomized clinical trials (RCTs) comparing non-surgical treatment of peri-implantitis alone versus NST plus any adjunctive method/treatment. The primary outcome was probing pocket depth (PPD) reduction. Results: Sixteen RCTs were included. Only 2 out of 1189 implants were lost and follow-up ranged from 3 to 12 months. PPD reduction across the studies varied from 0.17 to 3.1 mm, while defect resolution from 5.3% to 57.1%. Systemic antimicrobials were associated to higher PPD reduction (1.56 mm; [95% CI 0.24 to 2.89]; p = 0.02) with high heterogeneity, and treatment success (OR = 3.23; [95% CI 1.17 to 8.94]; p = 0.02), compared to NST alone. No differences were found with adjunctive local antimicrobials and lasers for PPD and bleeding on probing (BoP) reduction. Conclusions: Non-surgical treatment with or without adjunctive methods may reduce PPD and BoP even if complete resolution of the pocket is unpredictable. Among possible adjunctive methods, only systemic antibiotics seems to provide further benefits, but their usage should be considered with caution

A method for monitoring vascular access function during hemodialysis

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Correlation of Serum Cystatin C with Glomerular Filtration Rate in Patients Receiving Platinum-Based Chemotherapy

Objectives. Serum cystatin C seems to be an accurate marker of glomerular filtration rate (GFR) compared to serum creatinine. The aim of this work was to explore the possibility of using serum cystatin C instead of serum creatinine to early predict renal failure in cancer patients who received platinum based chemotherapy. Design and Methods. Serum creatinine, serum cystatin C concentrations, and GFR were determined simultaneously in 52 cancer patients received carboplatin-based or cisplatin-based chemotherapy. Serum creatinine was assayed on Cobas C6000-Roche, serum cystatin C assay was performed on AIA 360-Tosoh, and GFR was determined in all patients, before the first cycle of chemotherapy and before the subsequent administrations. Results. In the overall series, for the prediction of a fall of GFR < 80 mL/min/1.73 m2, the AUC of the ROC curve for cystatin C was 0,667 and the best threshold was 1.135 mg/L (sensitivity 90.5%, specificity 61.1%). For a GFR fall < 60 mL/min/1.73 m2, the AUC of ROC curve for cystatin C was 74.3% and the best threshold was 1.415 mg/L (sensitivity 66.7%, specificity 73.2%). Conclusions. Baseline cystatin C values were not able to predict renal failure during subsequent treatment. In conclusion, serum cystatin C is not a reliable early marker to efficiently predict renal failure in patients receiving chemotherapy

JAK3/STAT5/6 Pathway Alterations Are Associated with Immune Deviation in CD8+ T Cells in Renal Cell Carcinoma Patients

To investigate the molecular mechanisms underlying altered T cell response in renal cell carcinoma (RCC) patients, we compared autologous and allogeneic CD8+ T cell responses against RCC line from RCC patients and their HLA-matched donors, using mixed lymphocyte/tumor cell cultures (MLTCs). In addition, we analyzed the expression of molecules associated with cell cycle regulation. Autologous MLTC responder CD8+ T cells showed cytotoxic activity against RCC cell lines; however the analysis of the distribution of CD8+ T-cell subsets revealed that allogenic counterparts mediate superior antitumor efficacy. In RCC patients, a decreased proliferative response to tumor, associated with defects in JAK3/STAT5/6 expression that led to increased p27KIP1 expression and alterations in the cell cycle, was observed. These data define a molecular pathway involved in cell cycle regulation that is associated with the dysfunction of tumor-specific CD8+ effector cells. If validated, this may define a therapeutic target in the setting of patients with RCC

Dysbiosis Triggers ACF Development in Genetically Predisposed Subjects

Background: Colorectal cancer (CRC) is the third most common cancer worldwide, characterized by a multifactorial etiology including genetics, lifestyle, and environmental factors including microbiota composition. To address the role of microbial modulation in CRC, we used our recently established mouse model (the Winnie-APCMin/+) combining inflammation and genetics.Methods: Gut microbiota profiling was performed on 8-week-old Winnie-APCMin/+ mice and their littermates by 16S rDNA gene amplicon sequencing. Moreover, to study the impact of dysbiosis induced by the mother's genetics in ACF development, the large intestines of APCMin/+ mice born from wild type mice were investigated by histological analysis at 8 weeks.Results: ACF development in 8-week-old Winnie-APCMin/+mice was triggered by dysbiosis. Specifically, the onset of ACF in genetically predisposed mice may result from dysbiotic signatures in the gastrointestinal tract of the breeders. Additionally, fecal transplant from Winnie donors to APCMin/+ hosts leads to an increased rate of ACF development.Conclusions: The characterization of microbiota profiling supporting CRC development in genetically predisposed mice could help to design therapeutic strategies to prevent dysbiosis. The application of these strategies in mothers during pregnancy and lactation could also reduce the CRC risk in the offspring

Interleukin-1β blockade reduces intestinal inflammation in a murine model of Tumor Necrosis Factor-independent ulcerative colitis

Background &amp; aimsInflammatory bowel diseases (IBDs) are multifactorial diseases commonly treated with either immunomodulatory drugs or anti-tumor necrosis factor (TNF). Currently, failure to respond to anti-TNF therapy (assessed not prior to 8-12 weeks after starting treatment) occurs in 20-40% of patients enrolled in clinical trials and 10-20% in clinical practice. Murine models of IBD provide important tools to better understand disease mechanism(s). In this context and among the numerous models available, Winnie-TNF-KO mice were recently reported to display characteristics of ulcerative colitis (UC) that are independent of TNF, and with increased IL-1β production.MethodsHerein, the efficacy of recombinant (r) IL-1 receptor antagonist (IL-1Ra, Anakinra) administration was evaluated in Winnie-TNF-KO mice, utilized as an UC model of primary anti-TNF non-responders.ResultsWe analyzed gut mucosal biopsies and circulating cytokine profiles of a cohort of 30 UC patients; approximately 75% of primary non-responders were characterized by abundant IL-1β in both the serum and local intestinal tissues. In Winnie-TNF-KO mice, administration of Anakinra efficiently reduced the histological score of the distal colon, which represents the most common site of inflammation in Winnie mice. Furthermore, among lamina propria and mesenteric lymph node-derived T cells, IFNγ-expressing CD8+ T cells were significantly reduced following Anakinra administration.ConclusionsOur study provides new insight and alternative approaches to treat UC patients, and point to anti-IL-1 strategies (i.e., Anakinra) that may be a more effective therapeutic option for primary non-responders to anti-TNF therapy

Combined effect of obesity and diabetes on early breast cancer outcome: A prospective observational study

Background: Previous studies suggested that obesity and diabetes were correlated with breast cancer outcome. The aim of the present study was to investigate the prognostic effect of obesity and diabetes on the outcome of early breast cancer patients. Materials and Methods: Overall, 841 early breast cancer patients were prospectively enrolled between January 2009 and December 2013. Study population was divided into four groups: (1) patients without obesity or diabetes; (2) patients with only diabetes; (3) patients with only obesity; and (4) patients with both diabetes and obesity. Categorical variables were analyzed by the chi-square test and survival data by the log-rank test. Results: At diagnosis, obese and diabetic patients were more likely to be older (p < 0.0001) and post-menopausal (p < 0.0001) and to have a tumor larger than 2 cm (p < 0.0001) than patients in groups 1–3. At univariate analyses, obese and diabetic patients had a worse disease-free survival (p = 0.01) and overall survival (p = 0.001) than did patients without obesity and diabetes. At multivariate analyses, the co-presence of obesity and diabetes was an independent prognostic factor for diseasefree survival (hazard ratio=2.62, 95% CI 1.23–5.60) but not for overall survival. Conclusions: At diagnosis, patients with obesity and diabetes were older, had larger tumors and a worse outcome compared to patients without obesity or diabetes. These data suggest that metabolic health influences the prognosis of patients affected by early breast cance

Brazilian red propolis: extracts production, physicochemical characterization, and cytotoxicity profile for antitumor activity

Brazilian red propolis has been proposed as a new source of compounds with cytotoxic activity. Red propolis is a resinous material of vegetal origin, synthesized from the bees of the Appis mellifera family, with recognized biological properties. To obtain actives of low polarity and high cytotoxic profile from red propolis, in this work, we proposed a new solvent accelerated extraction method. A complete 23 factorial design was carried out to evaluate the influence of the independent variables or factors (e.g., temperature, number of cycles, and extraction time) on the dependent variable or response (i.e., yield of production). The extracts were analyzed by gas chromatography coupled with mass spectrometry for the identification of chemical compounds. Gas chromatography analysis revealed the presence of hydrocarbons, alcohols, ketones, ethers, and terpenes, such as lupeol, lupenone, and lupeol acetate, in most of the obtained extracts. To evaluate the cytotoxicity profile of the obtained bioactives, the 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide colorimetric assay was performed in different tumor cell lines (HCT116 and PC3). The results show that the extract obtained from 70 °C and one cycle of extraction of 10 min exhibited the highest cytotoxic activity against the tested cell lines. The highest yield, however, did not indicate the highest cytotoxic activity, but the optimal extraction conditions were indeed dependent on the temperature (i.e., 70 °C).FCT -Fundação para a Ciência e a Tecnologia(UIDB/04469/2020)info:eu-repo/semantics/publishedVersio

Nutritional Regimes Enriched with Antioxidants as an Efficient Adjuvant for IBD Patients under Infliximab Administration, a Pilot Study

Antioxidants are privileged candidates for the development of adjuvants able to improve the efficiency of pharmacological therapies, particularly for chronic inflammatory syndromes. During the last 20 years, anti-TNFα (tumor necrosis factor alpha) monoclonal antibodies infusion has been the biological therapy most frequently administered but there is still large space for improvement in disease remission rates and maintenance. In this context, nutritional bioactive compounds contained in dietary patterns or included as supplements, may act as adjuvants for the induction and maintenance of IBD (inflammatory bowel diseases) remission. To verify this possibility, a single-center preliminary study (SI-CURA, Soluzioni Innovative per la gestione del paziente e il follow up terapeutico della Colite UlceRosA) was designed and carried out to evaluate whether a daily administration of purple corn supplement could improve the response to Infliximab (IFX) infusion of IBD patients with both Crohn’s disease (CD) and ulcerative colitis (UC). A cohort of 47 patients was enrolled in the study. Biological samples were collected before the first and the third IFX infusion. All patients received nutritional guidelines, 27 of them received commercial red fruit tea with low anthocyanins content, while 20 received a purple corn supplement with a high anthocyanin content. Results show that the administration of an antioxidant-enriched purple corn supplement could improve IFX-mediated disease remission in terms of circulating inflammatory markers. Comparison between CD and UC patients revealed that, at this anthocyanin dosage, the purple corn extract administration improved the IFX response in CD but not in UC patients. Our results may pave the way for a new metacentric study of CD patients, recruiting a wider cohort and followed-up over a longer observational time