scholarly journals The Secretome Deregulations in a Rat Model of Endotoxemic Shock

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
A. Blangy-Letheule ◽  
A. Persello ◽  
S. Michelland ◽  
V. Cunin ◽  
F. Souab ◽  
...  
Keyword(s):  
Septic Shock ◽  
Large Scale ◽  
Biological Fluids ◽  
Predictive Biomarkers ◽  
Control Group ◽  
Label Free ◽  
Good Opportunity ◽  
Time Points ◽  
Arterial Blood ◽  
Endotoxemic Shock

Introduction. Septic shock is a systemic inflammatory response syndrome associated with organ failures. Earlier clinical diagnosis would be of benefit to a decrease in the mortality rate. However, there is currently a lack of predictive biomarkers. The secretome is the set of proteins secreted by a cell, tissue, or organism at a given time and under certain conditions. The plasma secretome is easily accessible from biological fluids and represents a good opportunity to discover new biomarkers that can be studied with nontargeted “omic” strategies. Aims. To identify relevant deregulated proteins (DEP) in the secretome of a rat endotoxemic shock model. Methods. Endotoxemic shock was induced in rats by intravenous injection of lipopolysaccharides (LPS, S. enterica typhi, 0.5 mg/kg) and compared to controls (Ringer Lactate, iv). Under isoflurane anesthesia, carotid cannulation allowed mean arterial blood pressure (MAP) and heart rate (HR) monitoring and blood sampling at different time points (T0 and T50 or T0 and T90, with EDTA and protease inhibitor). Samples were prepared for large-scale tandem mass spectrometry (MS-MS) based on a label-free quantification to allow identification of the proteins deregulated upon endotoxemic conditions. A Gene Ontology (GO) analysis defined several clusters of biological processes (BP) in which the DEP are involved. Results. Ninety minutes after shock induction, the LPS group presents a reduction in MAP (-45%, p < 0.05 ) and increased lactate levels (+27.5%, p < 0.05 ) compared to the control group. Proteomic analyses revealed 10 and 33 DEP in the LPS group, respectively, at 50 and 90 minutes after LPS injection. At these time points, GO-BP showed alterations in pathways involved in oxidative stress response and coagulation. Conclusion. This study proposes an approach to identify relevant DEP in septic shock and brings new insights into the understanding of the secretome adaptations upon sepsis.

scholarly journals METHODOLOGICAL ISSUES OF DETERMINING CONCENTRATIONS OF SOME CYTOKINES IN PERIPHERAL MBLOOD FROM HEALTHY INDIVIDUALS

2018 ◽  
Vol 20 (5) ◽  
pp. 763-774
Author(s):  
N. A. Arsentieva ◽  
Areg A. Totolian
Keyword(s):  
Blood Serum ◽  
Large Scale ◽  
Human Peripheral Blood ◽  
Biological Fluids ◽  
Control Group ◽  
Healthy Individuals ◽  
Serum Samples ◽  
Normal Ranges ◽  
Number Of Patients ◽  
Cytokine Levels

Cytokines are the most important factors in pathogenesis of infectious, allergic, autoimmune, lymphoproliferative diseases and immunopathological processes. Many cytokines are very useful therapeutic targets for immunodiagnostics of different human diseases. Measurement of the cytokine levels by immunochemical methods in various biological fluids is usually used for diagnostic evaluation. Content analysis of research articles from two Russian immunological journals, “Meditsinskaya Immunologiya” = “Medical Immunology (Russia)” and “Infektsiya i immunitet” = “Russian Journal of Infection and Immunity,”, shows that ELISA, xMAP multiplex immunoassay, and CBA technologies are the most common methods used in clinical and immunological studies aimed for determination of cytokine contents in blood serum/plasma. Normal ranges of some plasma/serum cytokines in healthy individuals were subject to wide variations when using different methods and specific reagents from various manufacturers. The normal ranges applied by the CBA-technology, are significantly higher than appropriate values obtained by ELISA or xMAP-technologies. Most studies included a small control group, usually limited by 15-20 persons. In most of these works, blood serum samples were used for assays, whereas EDTA-conserved plasma was taken only in few studies. It has been concluded that the results of cytokine measurements in blood serum/plasma in healthy individuals vary in wide ranges, and depend on many factors, e.g., initial sampling material, mode of technology, type of test systems, and characteristics of the group under study: number of patients, age, gender, geographical factor, etc. The mentioned data demonstrate a need for large-scale multicenter clinical studies, in order to standardize measurements of the cytokine levels in human peripheral blood and to specify their normal values.

scholarly journals Pharmacogenetics of Antidepressants: from Genetic Findings to Predictive Strategies

2019 ◽  
Vol 4 (2) ◽  
pp. 33-43
Author(s):  
L. K. Khokhlov ◽  
N. E. Lukyanov
Keyword(s):  
Large Scale ◽  
Depressive Disorders ◽  
Genome Wide Association Study ◽  
Treatment Effectiveness ◽  
Predictive Biomarkers ◽  
Genomic Research ◽  
Control Group ◽  
Variable Activity ◽  
Cytochrome P450 Family ◽  
Almost All

The constantly growing contribution of depressive disorders to the global disease statistics calls for a growth of treatment effectiveness and optimization. Antidepressants are the most frequently prescribed medicines for depressive disorders. However, development of a standardized pharmacotherapeutic approach is burdened by the genomic heterogeneity, lack of reliable predictive biomarkers and variability of the medicines metabolism aggravated by multiple side effects of antidepressants. According to modern assessments up to 20 % of the genes expressed in our brain are involved in the pathogenesis of depression. Large-scale genetic and genomic research has found a number of potentially prognostic genes. It has also been proven that the effectiveness and tolerability of antidepressants directly depend on the variable activity of the enzymes that metabolize medicines. Almost all modern antidepressants are metabolized by the cytochrome P450 family enzymes. The most promising direction of research today is the GWAS (Genome-Wide Association Study) method that is aimed to link genomic variations with phenotypical manifestations. In this type of research genomes of depressive patients with different phenotypes are compared to the genomes of the control group containing same age, sex and other parameters healthy people. Notably, regardless of the large cohorts of patients analyzed, none of the GWA studies conducted so far can reliably reproduce the results of other analogous studies. The explicit heterogeneity of the genes associated with the depression pathogenesis and their pleiotropic effects are strongly influenced by environmental factors. This may explain the difficulty of obtaining clear and reproducible results. However, despite any negative circumstances, the active multidirectional research conducted today, raises the hope of clinicians and their patients to get a whole number of schedules how to achieve remission faster and with guaranteed results

Salivary mir-27b Expression in Oral Lichen Planus Patients: A Series of Cases and a Narrative Review of Literature

2020 ◽  
Vol 19 (31) ◽  
pp. 2816-2823 ◽  
Author(s):  
Dario Di Stasio ◽  
Laura Mosca ◽  
Alberta Lucchese ◽  
Donatella Delle Cave ◽  
Hiromichi Kawasaki ◽  
...  
Keyword(s):  
Lichen Planus ◽  
Oral Lichen Planus ◽  
Inflammatory Diseases ◽  
Biological Fluids ◽  
Critical Role ◽  
Invasive Procedure ◽  
Control Group ◽  
Study Group ◽  
Immune Functions ◽  
Oral Lichen

Background: microRNAs play a critical role in auto-immunity, cell proliferation, differentiation and cell death. miRNAs are present in all biological fluids, and their expression is essential in maintaining regular immune functions and preventing autoimmunity, whereas miRNA dysregulation may be associated with the pathogenesis of autoimmune and inflammatory diseases. Oral lichen planus (OLP) is an inflammatory disease mediated by cytotoxic T cells attack against epithelial cells. The present study aims to perform a specific microRNA expression profile through the analysis of saliva in this disease. Methods: The study group was formed by five patients (mean age 62.8±1.98 years; 3 females/2 males) affected by oral lichen planus and control group by five healthy subjects (mean age 59.8 years±2.3; 3 females/ 2 males); using a low-density microarray analysis, we recorded a total of 98 differentially expressed miRNAs in the saliva of patients with oral lichen planus compared to the control group. The validation was performed for miR-27b with qRT-PCR in all saliva samples of oral lichen planus group. Results: 89 miRNAs were up-regulated and nine down-regulated. In details, levels of miR-21, miR- 125b, miR-203 and miR15b were increased (p<0.001) in study group while levels of miR-27b were about 3.0-fold decreased compared to controls (p<0.001) of miR-27b expression in OLP saliva. QRTPCR validation confirmed the down regulation of miR-27b in all saliva samples. Conclusions: Collecting saliva samples is a non-invasive procedure and is well accepted by all patients. microRNAs can be readily isolated and identified and can represent useful biomarkers of OLP.

Evaluation of Ovaries in Patients with Polycystic Ovary Syndrome using Shear Wave Elastography

2020 ◽  
Vol 16 (5) ◽  
pp. 578-583
Author(s):  
Aysegul Altunkeser ◽  
Zeynep Ozturk Inal ◽  
Nahide Baran
Keyword(s):  
Shear Wave ◽  
Large Scale ◽  
Polycystic Ovary ◽  
Shear Wave Elastography ◽  
Left Ovary ◽  
Control Group ◽  
Tissue Elasticity ◽  
Group I ◽  
Pcos Group ◽  
The Right

Background: Shear wave electrography (SWE) is a novel non-invasive imaging technique which demonstrate tissue elasticity. Recent research evaluating the elasticity properties of normal and pathological tissues emphasize the diagnostic importance of this technique. Aims: Polycystic ovarian syndrome (PCOS), which is characterized by menstrual irregularity, hyperandrogenism, and polycystic overgrowth, may cause infertility. The aim of this study was to evaluate the elasticity of ovaries in patients with PCOS using SWE. Methods: 66 patients diagnosed with PCOS according to the Rotterdam criteria (PCOS = group I) and 72 patients with non-PCOS (Control = group II), were included in the study. Demographic and clinical characteristics of the participants were recorded. Ovarian elasticity was assessed in all patients with SWE, and speed values were obtained from the ovaries. The elasticity of the ovaries was compared between the two groups. Results: While there were statistically significant differences between the groups in body mass index (BMI), right and left ovarian volumes, luteinizing hormone and testosterone levels (p<0.05), no significant differences were found between groups I and II in the velocity (for the right ovary 3.89±1.81 vs. 2.93±0.72, p=0.301; for the left ovary 2.88±0.65 vs. 2.95±0.80, p=0.577) and elastography (for the right ovary 36.62±17.78 vs. 36.79±14.32, p=0.3952; for the left ovary 36.56±14.15 vs. 36.26±15.10, p=0.903) values, respectively. Conclusion: We could not obtain different velocity and elastography values from the ovaries of the patients with PCOS using SWE. Therefore, further large-scale studies are needed to elucidate this issue.

scholarly journals Optimizing Manufacturing and Osseointegration of Ti6Al4V Implants through Precision Casting and Calcium and Phosphorus Ion Implantation? In Vivo Results of a Large-Scale Animal Trial

Materials ◽  
2020 ◽  
Vol 13 (7) ◽  
pp. 1670 ◽  
Author(s):  
Wölfle-Roos JV ◽  
Katmer Amet B ◽  
Fiedler J ◽  
Michels H ◽  
Kappelt G ◽  
...  
Keyword(s):  
Ion Implantation ◽  
Large Scale ◽  
In Vivo Studies ◽  
Control Group ◽  
Implant Surface ◽  
Precision Casting ◽  
Pull Out ◽  
Significant Difference ◽  
Calcium And Phosphorus

Background: Uncemented implants are still associated with several major challenges, especially with regard to their manufacturing and their osseointegration. In this study, a novel manufacturing technique—an optimized form of precision casting—and a novel surface modification to promote osseointegration—calcium and phosphorus ion implantation into the implant surface—were tested in vivo. Methods: Cylindrical Ti6Al4V implants were inserted bilaterally into the tibia of 110 rats. We compared two generations of cast Ti6Al4V implants (CAST 1st GEN, n = 22, and CAST 2nd GEN, n = 22) as well as cast 2nd GEN Ti6Al4V implants with calcium (CAST + CA, n = 22) and phosphorus (CAST + P, n = 22) ion implantation to standard machined Ti6Al4V implants (control, n = 22). After 4 and 12 weeks, maximal pull-out force and bone-to-implant contact rate (BIC) were measured and compared between all five groups. Results: There was no significant difference between all five groups after 4 weeks or 12 weeks with regard to pull-out force (p > 0.05, Kruskal Wallis test). Histomorphometric analysis showed no significant difference of BIC after 4 weeks (p > 0.05, Kruskal–Wallis test), whereas there was a trend towards a higher BIC in the CAST + P group (54.8% ± 15.2%), especially compared to the control group (38.6% ± 12.8%) after 12 weeks (p = 0.053, Kruskal–Wallis test). Conclusion: In this study, we found no indication of inferiority of Ti6Al4V implants cast with the optimized centrifugal precision casting technique of the second generation compared to standard Ti6Al4V implants. As the employed manufacturing process holds considerable economic potential, mainly due to a significantly decreased material demand per implant by casting near net-shape instead of milling away most of the starting ingot, its application in manufacturing uncemented implants seems promising. However, no significant advantages of calcium or phosphorus ion implantation could be observed in this study. Due to the promising results of ion implantation in previous in vitro and in vivo studies, further in vivo studies with different ion implantation conditions should be considered.

An Internet-based health gateway device for interactive communication and automatic data uploading: Clinical efficacy for type 2 diabetes in a multi-centre trial

2016 ◽  
Vol 23 (6) ◽  
pp. 595-604 ◽  
Author(s):  
Jae Hyoung Cho ◽  
Hun-Sung Kim ◽  
Seung Hyun Yoo ◽  
Chang Hee Jung ◽  
Woo Je Lee ◽  
...  
Keyword(s):  
Adverse Events ◽  
Healthcare System ◽  
Glucose Control ◽  
Large Scale ◽  
Diabetes Management ◽  
Intervention Group ◽  
Diabetes Control ◽  
Control Group ◽  
Anthropometric Parameters ◽  
Automatic Data

Introduction The aim of this study was to improve the quality of diabetes control and evaluate the efficacy of an Internet-based integrated healthcare system for diabetes management and safety. Methods We conducted a large-scale, multi-centre, randomized clinical trial involving 484 patients. Patients in the intervention group ( n = 244) were treated with the Internet-based system for six months, while the control group ( n = 240) received the usual outpatient management over the same period. HbA1c, blood chemistries, anthropometric parameters, and adverse events were assessed at the beginning of the study, after three months, and the end of the study. Results There were no initial significant differences between the groups with respect to demographics and clinical parameters. Upon six-month follow-up, HbA1c levels were significantly decreased from 7.86 ± 0.69% to 7.55 ± 0.86% within the intervention group ( p < 0.001) compared to 7.81 ± 0.66% to 7.70 ± 0.88% within the control group. Postprandial glucose reduction was predominant. A subgroup with baseline HbA1c higher than 8% and good compliance achieved a reduction of HbA1c by 0.8 ± 1.05%. Glucose control and waist circumference reduction were more effective in females and subjects older than 40 years of age. There were no adverse events associated with the intervention. Discussion This e-healthcare system was effective for glucose control and body composition improvement without associated adverse events in a multi-centre trial. This system may be effective in improving diabetes control in the general population.

scholarly journals Metabolic Evaluation of Urine from Patients Diagnosed with High Grade (HG) Bladder Cancer by SPME-LC-MS Method

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2194
Author(s):  
Kamil Łuczykowski ◽  
Natalia Warmuzińska ◽  
Sylwia Operacz ◽  
Iga Stryjak ◽  
Joanna Bogusiewicz ◽  
...  
Keyword(s):  
Thin Film ◽  
Bladder Cancer ◽  
High Performance ◽  
Biomarker Discovery ◽  
Solid Phase ◽  
Biological Fluids ◽  
Reversed Phase ◽  
Control Group ◽  
Metabolic Evaluation ◽  
Metabolomic Profiling

Bladder cancer (BC) is a common malignancy of the urinary system and a leading cause of death worldwide. In this work, untargeted metabolomic profiling of biological fluids is presented as a non-invasive tool for bladder cancer biomarker discovery as a first step towards developing superior methods for detection, treatment, and prevention well as to further our current understanding of this disease. In this study, urine samples from 24 healthy volunteers and 24 BC patients were subjected to metabolomic profiling using high throughput solid-phase microextraction (SPME) in thin-film format and reversed-phase high-performance liquid chromatography coupled with a Q Exactive Focus Orbitrap mass spectrometer. The chemometric analysis enabled the selection of metabolites contributing to the observed separation of BC patients from the control group. Relevant differences were demonstrated for phenylalanine metabolism compounds, i.e., benzoic acid, hippuric acid, and 4-hydroxycinnamic acid. Furthermore, compounds involved in the metabolism of histidine, beta-alanine, and glycerophospholipids were also identified. Thin-film SPME can be efficiently used as an alternative approach to other traditional urine sample preparation methods, demonstrating the SPME technique as a simple and efficient tool for urinary metabolomics research. Moreover, this study’s results may support a better understanding of bladder cancer development and progression mechanisms.

scholarly journals Effects of D-allulose on glucose tolerance and insulin response to a standard oral sucrose load: results of a prospective, randomized, crossover study

2021 ◽  
Vol 9 (1) ◽  
pp. e001939
Author(s):  
Francesco Franchi ◽  
Dmitry M Yaranov ◽  
Fabiana Rollini ◽  
Andrea Rivas ◽  
Jose Rivas Rios ◽  
...  
Keyword(s):  
Crossover Study ◽  
Plasma Glucose ◽  
Large Scale ◽  
Insulin Response ◽  
Mean Difference ◽  
Dietary Guidelines ◽  
Sugar Intake ◽  
Time Points ◽  
Insulin Levels ◽  
Dose Dependent

IntroductionCurrent dietary guidelines recommend limiting sugar intake for the prevention of diabetes mellitus (DM). Reduction in sugar intake may require sugar substitutes. Among these, D-allulose is a non-calorie rare monosaccharide with 70% sweetness of sucrose, which has shown anti-DM effects in Asian populations. However, there is limited data on the effects of D-allulose in other populations, including Westerners.Research design and methodsThis was a prospective, randomized, double-blind, placebo-controlled, crossover study conducted in 30 subjects without DM. Study participants were given a standard oral (50 g) sucrose load and randomized to placebo or escalating doses of D-allulose (2.5, 5.0, 7.5, 10.0 g). Subjects crossed-over to the alternate study treatment after 7–14 days of wash out. Plasma glucose and insulin levels were measured at five time points: before and at 30, 60, 90 and 120 min after ingestion.ResultsD-allulose was associated with a dose-dependent reduction of plasma glucose at 30 min compared with placebo. In particular, glucose was significantly lower with the 7.5 g (mean difference: 11; 95% CI 3 to 19; p=0.005) and 10 g (mean difference: 12; 95% CI 4 to 20; p=0.002) doses. Although glucose was not reduced at the other time points, there was a dose-dependent reduction in glucose excursion compared with placebo, which was significant with the 10 g dose (p=0.023). Accordingly, at 30 min D-allulose was associated with a trend towards lower insulin levels compared with placebo, which was significant with the 10 g dose (mean difference: 14; 95% CI 4 to 25; p=0.006). D-allulose did not reduce insulin at any other time point, but there was a significant dose-dependent reduction in insulin excursion compared with placebo (p=0.028), which was significant with the 10 g dose (p=0.002).ConclusionsThis is the largest study assessing the effects of D-allulose in Westerners demonstrating an early dose-dependent reduction in plasma glucose and insulin levels as well as decreased postprandial glucose and insulin excursion in subjects without DM. These pilot observations set the basis for large-scale investigations to support the anti-DM effects of D-allulose.Trial registration numberNCT02714413.

scholarly journals Effects of Polymyxin B Hemoperfusion on Septic Shock Patients Requiring Noradrenaline: Analysis of a Nationwide Administrative Database in Japan

2021 ◽  
pp. 1-6
Author(s):  
Kenji Fujimori ◽  
Kunio Tarasawa ◽  
Kiyohide Fushimi
Keyword(s):  
Septic Shock ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Polymyxin B ◽  
Administrative Database ◽  
Control Group ◽  
Continuous Hemodiafiltration ◽  
Significant Survival ◽  
Maximum Daily Dose ◽  
Polymyxin B Hemoperfusion

<b><i>Introduction:</i></b> Polymyxin B hemoperfusion (PMX) reduces endotoxin in septic shock patients’ blood and can improve hemodynamics and organ functions. However, its effects on the reduction of septic shock mortality are controversial. <b><i>Methods:</i></b> Using the Japanese diagnosis procedure combination database from April 2016 to March 2019, we identified adult septic shock patients treated with noradrenaline. This study used propensity score matching to compare the outcome between PMX-treated and non-treated patients. The primary endpoint was 28-day mortality, counting from the day of noradrenaline initiation. The secondary endpoints were noradrenaline-, ventilator-, and continuous hemodiafiltration (CHDF)-free days at day 28. <b><i>Results:</i></b> Of 30,731 eligible patients, 4,766 received PMX. Propensity score matching produced a matched cohort of 4,141 pairs with well-balanced patient backgrounds. The 28-day survival rate was 77.9% in the PMX group and 71.1% in the control group (<i>p</i> &#x3c; 0.0001). Median days of noradrenalin-, CHDF-, and ventilator-free days were 2 days (<i>p</i> &#x3c; 0.0001), 2 days (<i>p</i> &#x3c; 0.0001), and 6 days (<i>p</i> &#x3c; 0.0001) longer in the PMX group than in the control group, respectively. When stratified with the maximum daily dose of noradrenaline, the PMX group showed a statistically significant survival benefit in the groups with noradrenaline dose &#x3c;20 mg/day but not in the noradrenaline group dose ≥20 mg/day. <b><i>Conclusion:</i></b> Analysis of large Japanese databases showed that septic shock patients who received noradrenaline might benefit from PMX treatment.

scholarly journals The combined detection of Amphiregulin, Cyclin A1 and DDX20/Gemin3 expression predicts aggressive forms of oral squamous cell carcinoma

2021 ◽  
Author(s):  
Ekaterina Bourova-Flin ◽  
Samira Derakhshan ◽  
Afsaneh Goudarzi ◽  
Tao Wang ◽  
Anne-Laure Vitte ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell ◽  
Large Scale ◽  
Biomarker Discovery ◽  
Gene Expression Signature ◽  
Predictive Biomarkers ◽  
Specific Gene ◽  
Specific Expression ◽  
Intrinsic Nature ◽  
Independent Cohort

Abstract Background Large-scale genetic and epigenetic deregulations enable cancer cells to ectopically activate tissue-specific expression programmes. A specifically designed strategy was applied to oral squamous cell carcinomas (OSCC) in order to detect ectopic gene activations and develop a prognostic stratification test. Methods A dedicated original prognosis biomarker discovery approach was implemented using genome-wide transcriptomic data of OSCC, including training and validation cohorts. Abnormal expressions of silent genes were systematically detected, correlated with survival probabilities and evaluated as predictive biomarkers. The resulting stratification test was confirmed in an independent cohort using immunohistochemistry. Results A specific gene expression signature, including a combination of three genes, AREG, CCNA1 and DDX20, was found associated with high-risk OSCC in univariate and multivariate analyses. It was translated into an immunohistochemistry-based test, which successfully stratified patients of our own independent cohort. Discussion The exploration of the whole gene expression profile characterising aggressive OSCC tumours highlights their enhanced proliferative and poorly differentiated intrinsic nature. Experimental targeting of CCNA1 in OSCC cells is associated with a shift of transcriptomic signature towards the less aggressive form of OSCC, suggesting that CCNA1 could be a good target for therapeutic approaches.

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