Prediction and validation of microbial community function from normal pulp to pulpitis caused by deep dentinal caries

alexandrossfakianakis shared this article with you from Inoreader Prediction and validation of microbial community function from normal pulp to pulpitis caused by deep dentinal caries via International Endodontic Journal Abstract Introduction Microbial function changes may be responsible for dental pulp transformation from normal to diseased. However, studies on the prediction and verification of the function of the microbial community in the deep dentine and pulp of caries-induced pulpitis are lacking. Methods This study included 171 cases of deep dentinal caries divided into normal pulp (NP), reversible pulpitis (RP), and irreversible pulpitis (IRP). In Experiment I, the microbial-community composition was identified in 111 samples using 16S ribosomal DNA. Function prediction was performed through phylogenetic investigation of communities by PICRUSt prediction and qPCR. In Experiment II, different microbiome functions were confirmed in 60 samples using liquid chromatography-tandem mass spectrometry. Results In Experiment I, microbial abundance significantly differed in the IRP group compared to the other two groups. The RP and NP groups had the same microbiome composition, but the predicted functional difference between the RP and NP groups pertained to membrane transport (P<0.010). The predicted functional difference between the IRP and NP groups pertained to amino-acid, co-factor, and vitamin metabolism (P<0.010). In Experiment II, Kyoto Encyclopedia of Genes and Genomes functional annotation revealed that the differential metabolites between the RP and NP groups did not participate in membrane transport; however, the differential metabolites between the IRP and NP groups participated in amino-acid metabolism. Conclusions The near-pulp microbiome in RP and NP with deep dentinal caries had the same differential function. However, amino acid metabolism in near the pulp microbial community differed between IRP and NP with deep dentinal caries. View on Web

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Outcomes of relapsed/refractory extracranial germ cell tumors treated on conventional salvage chemotherapy without stem cell rescue: Experience from a tertiary cancer center

alexandrossfakianakis shared this article with you from Inoreader Outcomes of relapsed/refractory extracranial germ cell tumors treated on conventional salvage chemotherapy without stem cell rescue: Experience from a tertiary cancer center via Pediatric Blood & Cancer Abstract Background and aims Data on the outcome and prognostic indicators in extracranial relapsed/refractory germ cell tumors (rel/ref-GCTs) in children are limited to a few studies. This study looks at remission rates and outcomes of rel/ref-GCTs treated with conventional salvage chemotherapy (SC) regimens without stem cell rescue at a single center in the developing world. Methods Patients treated at our center from January 2009 to December 2018 were included. Risk at primary presentation was stratified as all completely excised teratomas and stage I gonadal tumors being low risk (LR); stage IV ovarian, stage III–IV extragonadal GCTs as high risk (HR), and the remaining as intermediate risk (IR). SC regimens were: vinblastine–ifosfamide–cisplatin/carboplatin or paclitaxel–ifosfamide–cisplatin/carboplatin, or cisplatin/carboplatin–etoposide–bleomycin. Local therapy was either surgery and/or radiotherapy. Results The analyzable cohort comprised 50 patients (44 = rel-GCTs; 6 = ref-GCTs) with a median age of 3.8 years and male:female ratio of 1.27:1. Primary location was ovary in 16 (32%), testicular in 10 (20%), and extragonadal in the rest (48%). Local, metastatic, and combined progression was noted in 28 (56%), 14 (28%), and eight (16%) patients, respectively, at a median time of 8.5 months. At a median follow-up of 60 months, the 5-year event-free survival (EFS) and overall survival (OS) of the entire cohort (n = 50) were 42.4% and 50.0%, respectively. In patients previously exposed to platinum analogs (n = 38), 5-year-EFS and OS were 27.7% and 31.7%, respectively. Local relapses did better when compared to metastatic and combined relapses (5-year EFS: 64% vs. 23% vs. 0%; p = .009). LR and IR tumors did better compared to HR (5-year EFS: 81.5% vs. 49.3% vs. 6.5%; p = .002). Patients with normalization of t umor markers after two cycles had a superior EFS (57.6% vs. 0%; p < .001). Relapsed tumors fared better than primary refractory GCTs (5-year EFS: 48.6% vs. 0%; p < .001). Conclusions Primary refractory GCTs, extragonadal rel-GCTs, and rel/ref-GCTs with a poor biochemical response did poorly with conventional SC and need alternative treatment strategies. The rel/ref-testicular GCTs had the best chance of salvage despite a second recurrence (5-year EFS and OS: 28.60% and 42.90%, respectively). View on Web

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Exogenous fetuin‐A protects against sepsis‐induced myocardial injury by inhibiting oxidative stress and inflammation in mice

alexandrossfakianakis shared this article with you from Inoreader Exogenous fetuin‐A protects against sepsis‐induced myocardial injury by inhibiting oxidative stress and inflammation in mice via Fundamental & Clinical Pharmacology Abstract Sepsis-induced myocardial injury is a consequence of septicemia and is one of the major causes of death in intensive care units. A serum glycoprotein called fetuin-A is secreted largely by the liver, tongue, placenta, and adipose tissue. Fetuin-A has a variety of biological and pharmacological properties. The anti-inflammatory and antioxidant glycoprotein fetuin-A has shown its efficacy in a number of inflammatory disorders including sepsis. However, its protective role against sepsis-induced myocardial injury remains elusive. The purpose of this work is to explore the role of fetuin-A in mouse models of myocardial injury brought on by cecal ligation and puncture (CLP). CLP significantly induced the myocardial injury assessed in terms of elevated myocardial markers (serum CK-MB, cTnI levels), inflammatory markers (IL-6, TNF-α) in the serum, and oxidative stress markers (increased MDA levels and decreased reduced glutathione) in heart tissue homogenate following 24 hours of ligati on and puncture. Further, hematoxylin and eosin (H&E) staining showed considerable histological alterations in the myocardial tissue of sepsis-developed mice. Interestingly, fetuin-A pretreatment (50 and 100 mg/kg) for four days before the CLP procedure significantly improved the myocardial injury and was evaluated in perspective of a reduction in the CK-MB, cTnI levels, IL-6, and TNF-α in sepsis-developed animals. Fetuin-A pretreatment significantly attenuated the oxidative stress and improved the myocardial morphology in a dose-dependent manner. The present study provides preliminary evidence that fetuin-A exerts protection against sepsis-induced cardiac dysfunction in vivo via suppression of inflammation and oxidative damage. View on Web

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Cardia and non‐cardia gastric cancer risk associated with Helicobacter pylori in East Asia and the West: A systematic review, meta‐analysis, and estimation of population attributable fraction

alexandrossfakianakis shared this article with you from Inoreader Cardia and non‐cardia gastric cancer risk associated with Helicobacter pylori in East Asia and the West: A systematic review, meta‐analysis, and estimation of population attributable fraction via Helicobacter Abstract Objectives To assess the region-specific relative risk of cardia/non-cardia gastric cancer (CGC/NCGC) associated with Helicobacter pylori (H. pylori) and quantify its contribution to gastric cancer burden using population attributable fraction (PAF). Methods PubMed, EMBASE, Web of Science, and Cochrane Central databases were searched by two reviewers until April 20, 2022. The association between H. pylori infection and NCGC/CGC was assessed using pooled odds ratios (ORs) with 95% confidence intervals (CIs). PAF was calculated using the formula of H. pylori prevalence and the pooled OR. Results One hundred and eight studies were included. A significant association was observed between H. pylori infection and NCGC in East Asia (OR, 4.36; 95% CI: 3.54–5.37) and the West (OR, 4.03; 95% CI: 2.59–6.27). Regarding CGC, a significant association was found only in East Asia (OR, 2.86; 95% CI: 2.26–3.63), not in the West (OR, 0.80; 95% CI: 0.61–1.05). For studies with a follow-up time of ≥10 years, pooled ORs for NCGC and CGC in East Asia were 5.58 (95% CI: 4.08–7.64) and 3.86 (95% CI: 2.69–5.55), respectively. Pooled OR for NCGC was 6.80 (95% CI: 3.78–12.25) in the West. PAFs showed that H. pylori infection accounted for 71.2% of NCGC, 60.7% of CGC in East Asia, and 73.2% of NCGC in the West. Conclusions Gastric cancer burden associated with H. pylori infection exhibits important geographical differences. Prolonged follow-up period could overcome the underestimation of the magnitude of the association between H. pylori infection and CGC/NCGC. Customized strategies for H. pylori screening and eradication should be implemented to prevent gastric cancer. View on Web

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Neuroinflammation related to the blood‐brain barrier and sphingosine‐1‐phosphate in a pre‐clinical model of periodontal diseases and depression in rats.

alexandrossfakianakis shared this article with you from Inoreader Neuroinflammation related to the blood‐brain barrier and sphingosine‐1‐phosphate in a pre‐clinical model of periodontal diseases and depression in rats. via Journal of Clinical Periodontology ABSTRACT Aim To explore the potential mechanisms of neuroinflammation (microglia, blood-brain barrier [BBB] permeability, and the sphingosine-1-phosphate [S1P] pathways) resulting from the association between periodontitis and depression in rats. Materials and methods This pre-clinical in vivo experimental study used Wistar rats, in which experimental periodontitis (P) was induced by using oral gavages with Porphyromonas gingivalis and Fusobacterium nucleatum. Then a chronic mild stress (CMS) model was implemented to induce depressive-like behavior, resulting in four groups: P with CMS (P+CMS+), P without CMS (P+CMS-), CMS without P (P-CMS+), and controls (P-CMS-). After harvesting brain samples, Protein/mRNA expression analyses and fluorescence immunohistochemistry were performed in the frontal cortex (FC). Results were analyzed by ANOVA tests. Results CMS exposure increased the number of microglia (an indicator of neuroinflammation) in the FC. In the combined model (P+CMS+), there was a decrease in the expression of tight junction proteins (zonula occludens-1 [ZO-1], occludin) and an increase in intercellular and vascular cell adhesion molecules (ICAM-1, VCAM-1) and matrix metalloproteinase 9 (MMP9), suggesting a more severe disruption of the BBB. The enzymes and receptors of S1P were also differentially regulated. Conclusions Microglia, BBB permeability, and S1P pathways could be relevant mechanisms explaining the association between periodontitis and depression. This article is protected by copyright. All rights reserved. View on Web

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Pharmacokinetic and pharmacodynamic study of 3 products of epoetin alfa as single subcutaneous dose in healthy volunteers

alexandrossfakianakis shared this article with you from Inoreader Pharmacokinetic and pharmacodynamic study of 3 products of epoetin alfa as single subcutaneous dose in healthy volunteers via Fundamental & Clinical Pharmacology Abstract Background Hemax® is an epoetin alfa product developed by Biosidus S.A. in Argentina at the end of the 1980's and has been present in that market since 1991. The initial presentation was a lyophilized powder containing albumin as stabilizer, to best adapt to environmental conditions in developing countries; more recently, a prefilled syringe, albumin-free presentation was developed, since this presentation has become the preferred standard in many markets. Objective The primary objective was to compare the pharmacokinetic profile of different formulations of epoetin alfa after a single subcutaneous administration to healthy volunteers of 40,000 IU of Eprex/Erypo® and Hemax® PFS. Methods This clinical trial was conceived following an open label, randomized, 3-way 3-period cross-over balanced, and sequential design. The study was conducted on 24 healthy volunteers. Results To analyze similarity between Hemax® PFS and the innovator product, Eprex®, AUC and Cmax of both products have been compared. The 90%CI lower limit for the geometric mean ratios was higher than 80% for any comparisons and the 90%CI upper limit for these geometric ratios was below 125% for all the comparisons made, thus demonstrating equivalence between both products. Conclusion The comparison between Hemax® PFS and Eprex® resulted in similar 90%CI for Cmax, AUC(0-120 h) and AUC(0-inf) ratios, all of them within the 80-125% interval, with a power above 95% for each ratio. These findings suggest biosimilar patterns for absorption velocity (with Tmax close to 15 h), absorption extent and elimination (with an elimination half-life close to 25-30 h for each formulation) View on Web

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Myeloid Phenotypes in Tracheostomy‐Associated Granulation Tissue

alexandrossfakianakis shared this article with you from Inoreader Myeloid Phenotypes in Tracheostomy‐Associated Granulation Tissue via The Laryngoscope In patients with indwelling tracheostomy, granulation tissue is a common, recurrent problem that may lead to multiple surgeries, difficulties with decannulation, and even wound contracture leading to stenosis at the site of prosthesis. This study demonstrates that alternatively activated M2 macrophages are increased in airway granulation tissue as determined by gene expression analysis of canonical biomarkers and cell surface antigens assessed by flow cytometry and immunohistochemistry. The monocyte cell populations associated with granulation tissue are predominantly classical subtype and the majority of macrophages were positive for pro-inflammatory marker S100A8/A9 with 36% of macrophages co-localizing the biomarker CD169+, highlighting these cell population as potential therapeutic targets for airway granulation tissue. Objective(s) Tracheostomy-associated granulation tissue is a common, recurrent problem occurring secondary to chronic mucosal irritation. Although granulation tissue is composed of predominantly innate immune cells, the phenotype of monocytes and macrophages in tracheostomy-associated granulation tissue is unknown. This study aims to define the myeloid cell population in granulation tissue secondary to tracheostomy. Methods Granulation tissue biopsies were obtained from 8 patients with tracheostomy secondary to laryngotracheal stenosis. Cell type analysis was performed by flow cytometry and gene expression was measured by quantitative real-time polymerase chain reaction. These methods and immunohistochemistry were used to define the monocyte/macrophage population in granulation tissue and were compared to tracheal autopsy control specimens. Results Flow cytometry demonstrated macrophages (CD45+CD11b+) and monocytes (CD45+FSClowSSClow) represent 23.2 ± 6% of the granulation tissue cell population. The M2 phenotype (CD206) is present in 77 ± 11% of the macrophage population and increased compared to the M1 phenotype (p = 0.012). Classical monocytes (CD45+CD14highCD16low) were increased in granulation tissue compared to controls (61.2 ± 7% and 30 ± 8.5%, p = 0.038). Eighty-five percent of macrophages expressed pro-inflammatory S100A8/A9 and 36 ± 4% of macrophages co-localized CD169, associated with tissue-resident macrophages. M2 gene expression (Arg1/CD206) was increased in granulation tissue (3.7 ± 0.4, p = 0.035 and 3.5 ± 0.5, p = 0.047) whereas M1 gene expression (CD80/CD86) was similar to controls (p = 0.64, p = 0.3). Immunohistochemistry of gra nulation tissue demonstrated increased cells co-localizing CD11b and CD206. Conclusions M2 macrophages are the dominant macrophage phenotype in tracheostomy-associated granulation tissue. The role of this cell type in promoting ongoing inflammation warrants future investigation to identify potential treatments for granulation tissue secondary to tracheostomy. Level of Evidence 3 Laryngoscope, 2023 View on Web

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