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1.
Line Engelbrechtsen Eva Pers Winning Iepsen Ehm A. Andersson Yuvaraj Mahendran Julie Lundgren Anna Elisabet Jonsson Sten Madsbad Jens Juul Holst Henrik Vestergaard Torben Hansen Signe Sørensen Torekov 《Metabolomics : Official journal of the Metabolomic Society》2016,12(12):181
Introduction
Increased levels of circulating branched chain amino acids (BCAAs), as well as phenylalanine, and tyrosine have been suggested to be involved in the pathogenesis of insulin resistance and type 2 diabetes. However, it is unknown how these metabolites are affected by weight loss, and during weight-maintaining treatment with glucagon-like peptide-1 receptor agonist (GLP-1 RA).Objective
We aimed to characterize changes in metabolites related to protein turnover and glycolysis after a weight loss intervention followed by long term weight maintenance with/without GLP-1 RA.Methods
Fifty-eight obese individuals underwent a diet-induced 12 % body weight loss during 8 weeks. Participants were randomized to weight maintenance with or without administration of the GLP-1 RA liraglutide (1.2 mg/day) for 52 weeks. Metabolomic profiling by high-throughput proton nuclear magnetic resonance spectroscopy was used for quantification of metabolites.Results
The weight loss was maintained in both groups and was associated with 9–20 % decreases in plasma concentrations of alanine, phenylalanine, histidine, tyrosine and the BCAAs leucine, isoleucine and valine (p < 0.05). Plasma citrate levels increased during weight loss (p = 5.2 × 10?15) and showed inverse correlation with insulin resistance measured by HOMA–IR levels (r = ?0.318, p = 0.025). Valine concentrations were lower in the control group compared to the GLP-1RA group during weight maintenance (p = 0.005).Conclusion
Weight loss is associated with marked changes in plasma concentrations of eight amino acids and glycolysis-related metabolites. Levels of the suggested type 2 diabetes risk markers (BCAAs) remain low during long-term weight maintenance.2.
Liming Weng Yan Gong Jeffrey Culver Stephen J. Gardell Christopher Petucci Alison M. Morse Reginald F. Frye Stephen T. Turner Arlene Chapman Eric Boerwinkle John Gums Amber L. Beitelshees Peggy R. Borum Julie A. Johnson Timothy J. Garrett Lauren M. McIntyre Rhonda M. Cooper-DeHoff 《Metabolomics : Official journal of the Metabolomic Society》2016,12(10):160
Introduction
Atenolol, a commonly prescribed β blocker for hypertension, is also associated with adverse cardiometabolic effects such as hyperglycemia and dyslipidemia. Knowledge of the mechanistic underpinnings of these adverse effects of atenolol is incomplete.Objective
We sought to identify biomarkers associated with risk for these untoward effects of atenolol. We measured baseline blood serum levels of acylcarnitines (ACs) that are involved in a host of different metabolic pathways, to establish associations with adverse cardiometabolic responses after atenolol treatment.Methods
Serum samples from Caucasian hypertensive patients (n = 224) who were treated with atenolol in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study were interrogated using a quantitative LC/MS assay for a large number of unique ACs in serum. For the 23 ACs that were detected in serum from ≥80 % of all patients, we conducted linear regression for changes in cardiometabolic factors with baseline AC levels, baseline cardiometabolic factors, age, sex, and BMI as covariates. For the 5 ACs that were detected in serum from 20 to 79 % of the patients, we similarly modeled changes in cardiometabolic factors, but with specifying the AC as present/absent in the regression.Results
Among the 28 ACs, the presence (vs. absence) of arachidonoyl-carnitine (C20:4) was significantly associated with increased glucose (p = 0.0002), and was nominally associated with decreased plasma HDL-C (p = 0.017) and with less blood pressure (BP) lowering (p = 0.006 for systolic BP, p = 0.002 for diastolic BP), after adjustment.Conclusion
Serum level of C20:4 is a promising biomarker to predict adverse cardiometabolic responses including glucose and poor antihypertensive response to atenolol.3.
Background
Complications of ostomy significantly affect the quality of life of ostomates. There is little evidence on the rate of long-term complications in ostomates, especially from the developing countries which include Sri Lanka. This study was aimed to describe the long-term complications of enteral ostomies and their contributory factors.Methods
A retrospective analysis was carried out on 192 patients who underwent ostomy creation over a period of 5 years. Data on type of complications, age, sex, type of ostomy, type of surgery and perioperative care by enteric stoma therapist were gathered. Associations were established using Chi square test and multiple logistic regression.Results
Out of 192 patients, only 146 patients presented regularly for follow up. The mean follow up duration was 28 months (range: 3–183). Around 34.2% developed surgical long-term complications related to the ostomy. Common complications were prolapse (n = 24, 16.4%), skin excoriation (n = 22, 15.1%) and parastomal hernia (n = 14, 9.6%). Overall complication rate was significantly less in loop ostomies (p < 0.05) and defunctioning ostomies (p < 0.05). Skin excoriation was significantly high in males (p < 0.05) and in ileostomies (p < 0.001). Parastomal hernia was commoner in end ostomies (p < 0.05). Perioperative care by enteric stoma therapist reduced the overall and specific complications (p < 0.001).Conclusion
The overall complication rate in our cohort of patients was 34.2%. The perioperative care of a stoma therapist may be very effective in preventing complications particularly in a setting with limited resources.4.
Karan S. Rana Chathyan Pararasa Islam Afzal David A. Nagel Eric J. Hill Clifford J. Bailey Helen R. Griffiths Ioannis Kyrou Harpal S. Randeva Srikanth Bellary James E. Brown 《Cardiovascular diabetology》2017,16(1):147
Background
Irisin is a hormone released mainly from skeletal muscle after exercise which increases adipose tissue energy expenditure. Adipocytes can also release irisin after exercise, acting as a local adipokine to induce white adipose tissue to take on a brown adipose tissue-like phenotype, suggesting that irisin and its receptor may represent a novel molecular target for the treatment of obesity and obesity-related diabetes. Previous reports provide conflicting evidence regarding circulating irisin levels in patients with type 2 diabetes (T2DM).Methods
This study investigated plasma irisin concentrations in 79 T2DM individuals, assessing potential associations with measures of segmental body composition, markers of endothelial dysfunction and peripheral blood mononuclear cell telomere length (TL).Results
Resting, overnight-fasted plasma irisin levels were significantly higher in this group of T2DM patients compared with levels we previously reported in healthy volunteers (p < 0.001). Moreover, plasma irisin displayed a positive correlation with body mass index (p = 0.04), body fat percentage (p = 0.03), HbA1c (p = 0.03) and soluble E-selectin (p < 0.001). A significant negative association was observed between plasma irisin and visceral adiposity (p = 0.006) in T2DM patients. Multiple regression analysis revealed that circulating soluble E-selectin levels could be predicted by plasma irisin (p = 0.004). Additionally, cultured human umbilical vein endothelial cells (HUVEC) exposed to 200 ng/ml irisin for 4 h showed a significant fourfold increase in E-selectin and 2.5-fold increase in ICAM-1 gene expression (p = 0.001 and p = 0.015 respectively), and there was a 1.8-fold increase in soluble E-selectin in conditioned media (p < 0.05).Conclusion
These data suggest that elevated plasma irisin in T2DM is associated with indices of adiposity, and that irisin may be involved in pro-atherogenic endothelial disturbances that accompany obesity and T2DM. Accordingly, irisin may constitute a potentially novel therapeutic opportunity in the field of obesity and cardiovascular diabetology.5.
Stewart F. Graham Olivier P. Chevallier Praveen Kumar Onur Türkoğlu Ray O. Bahado-Singh 《Metabolomics : Official journal of the Metabolomic Society》2016,12(4):62
Introduction
Autism spectrum disorders (ASD) is a group of neurodevelopmental disorders believed to have a multifactorial basis. Presently, diagnosis is based on behavioral and developmental signs in children before the age of 3 and no reliable clinical biomarkers are available for early detection.Objectives
This study aimed to biochemically profile the cerebellum from post-mortem human brain from ASD sufferers (n = 11) and compare their profiles to that of age-matched controls (n = 11) with no known brain disorder.Methods
Using liquid chromatography combined with LTQ-Orbitrap mass spectrometry we detected 14,328 features in ESI+ mode in polar extracts of post-mortem brain.Results
Of these only 37 were found to be statistically significantly different between ASD and controls (p < 0.05; fdr < 0.05). A panel of four features had a predictive power of 96.64 %, following statistical cross validation, for ASD detection. This model produced an AUC = 0.874 (CI 0.768–0.944) and a Fisher’s exact score of p = 4.50E?29.Conclusion
Whilst at this time we were unable to chemically identify the four features of interest we believe that this study underscores the potential value of high resolution metabolomics for the study of ASD. Further characterization of the polar metabolome of post mortem ASD brains could lead to the identification of potential biomarkers and novel therapeutics for the disease. The development of accurate biomarkers could assist in the early detection of ASD and promote early intervention strategies to improve outcome.6.
Hong-Bin?Cheng Rong-Yi?Chen Jing-Ping?Wu Li?Chen Yan-Hua?Liang Hai-Feng?Pan Zi-Feng?Pan Qing-Hua?Zhang Qing?Li Tian-Xi?Du Yong-Mei?Lv
Background
Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease. Complement component 4 (C4) has be proved to play a role in pathogenesis of SLE. In the present study, we investigated the effect of C4 on T cells differentiation.Methods
Thirty SLE patients were included in this study. CD4+ T cells were isolated from healthy subjects, and dendritic cells (DCs) were isolated from healthy subjects or SLE patients. C4 was supplemented to co-incubate with T cells and DCs.Results
Serum C4 concentration was positively correlated with regulatory T cell (Treg) percentage (R2 = 0.5907, p < 0.001) and TGFβ concentration (R2 = 0.5641, p < 0.001) in SLE patients. Different concentrations of C4 had no effect on T cells differentiation. Co-incubated T cells with DCs and C4 for 7 days, the Treg percentage and TGF-β concentration were significantly elevated. In addition, pre-treated DCs (from healthy subjects or SLE patients) with C4 and then co-incubated with T cells, the increases of Treg percentage and TGF-β concentration were also observed.Conclusion
C4 takes part in T cells differentiation to Treg cells via DCs.7.
Tomas Kovarnik Zhi Chen Gary S. Mintz Andreas Wahle Kristyna Bayerova Ales Kral Martin Chval Karel Kopriva John Lopez Milan Sonka Ales Linhart 《Cardiovascular diabetology》2017,16(1):156
Background
Coronary atherosclerosis progresses faster in patients with diabetes mellitus (DM) and causes higher morbidity and mortality in such patients compared to non-diabetics ones (non-DM). We quantify changes in plaque volume and plaque phenotype during lipid-lowering therapy in DM versus non-DM patients using advanced intracoronary imaging.Methods
We analyzed data from 61 patients with stable angina pectoris included to the PREDICT trial searching for prediction of plaque changes during intensive lipid-lowering therapy (40 mg rosuvastatin daily). Geometrically correct, fully 3-D representation of the vascular wall surfaces and intravascular ultrasound virtual histology (IVUS-VH) defined tissue characterization was obtained via fusion of two-plane angiography and IVUS-VH. Frame-based indices of plaque morphology and virtual histology analyses were computed and averaged in 5 mm long baseline/follow-up registered vessel segments covering the entire length of the two sequential pullbacks (baseline, 1-year). We analyzed 698 5-mm-long segments and calculated the Liverpool active plaque score (LAPS).Results
Despite reaching similar levels of LDL cholesterol (DM 2.12 ± 0.91 mmol/l, non-DM 1.8 ± 0.66 mmol/l, p = 0.21), DM patients experienced, compared to non-DM ones, higher progression of mean plaque area (0.47 ± 1.15 mm2 vs. 0.21 ± 0.97, p = 0.001), percent atheroma volume (0.7 ± 2.8% vs. ? 1.4 ± 2.5%, p = 0.007), increase of LAPS (0.23 ± 1.66 vs. 0.13 ± 1.79, p = 0.018), and exhibited more locations with TCFA (Thin-Cap Fibro-Atheroma) plaque phenotype in 5 mm vessel segments (20.3% vs. 12.5%, p = 0.01). However, only non-DM patients reached significant decrease of LDL cholesterol. Plaque changes were more pronounced in PIT (pathologic intimal thickening) compared to TCFA with increased plaque area in both phenotypes in DM patients.Conclusion
Based on detailed 3D analysis, we found advanced plaque phenotype and further atherosclerosis progression in DM patients despite the same reached levels of LDLc as in non-DM patients. Trial registration ClinicalTrials.gov identifier: NCT017735128.
Miguel A. Velasco Rafael Raya Luca Muzzioli Daniela Morelli Abraham Otero Marco Iosa Febo Cincotti Eduardo Rocon 《Biomedical engineering online》2017,16(1):74
Background
This paper presents the preliminary results of a novel rehabilitation therapy for cervical and trunk control of children with cerebral palsy (CP) based on serious videogames and physical exercise.Materials
The therapy is based on the use of the ENLAZA Interface, a head mouse based on inertial technology that will be used to control a set of serious videogames with movements of the head.Methods
Ten users with CP participated in the study. Whereas the control group (n = 5) followed traditional therapies, the experimental group (n = 5) complemented these therapies with a series of ten sessions of gaming with ENLAZA to exercise cervical flexion–extensions, rotations and inclinations in a controlled, engaging environment.Results
The ten work sessions yielded improvements in head and trunk control that were higher in the experimental group for Visual Analogue Scale, Goal Attainment Scaling and Trunk Control Measurement Scale (TCMS). Significant differences (27% vs. 2% of percentage improvement) were found between the experimental and control groups for TCMS (p < 0.05). The kinematic assessment shows that there were some improvements in the active and the passive range of motion. However, no significant differences were found pre- and post-intervention.Conclusions
Physical therapy that combines serious games with traditional rehabilitation could allow children with CP to achieve larger function improvements in the trunk and cervical regions. However, given the limited scope of this trial (n = 10) additional studies are needed to corroborate this hypothesis.9.
Julián Varas Pablo Achurra Felipe León Richard Castillo Natalia De La Fuente Rajesh Aggarwal Leticia Clede María P. Bravo Marcia Corvetto Rodrigo Montaña 《Annals of surgical innovation and research》2016,10(1):2
Background
Central venous catheterization (CVC) is a basic requirement for many medical specialties. Simulated training in CVC may allow the acquisition of this competency but few reports have established a valid methodology for learning and acquiring procedural skills for CVC. This study aims to validate the use of a tracking motion device, the imperial college surgical assessment device (ICSAD), by comparing it with validated global rating scales (GRS) to measure CVC performance in a simulated torso.Methods
Senior year medical students, first and last year residents (PGY1, LYR), and expert anesthesiologists performed a jugular CVC assessment in a simulated model (Laerdal IV Torso). A validated GRS for objective assessment of technical skills and motion analysis by ICSAD was used. Statistical analysis was performed through Mann–Whitney and Kruskal–Wallis tests for construct validity and Spearman correlation coefficients between the ICSAD and GRS scores for concurrent validity between both.Results
32 subjects were recruited (10 medical students, 8 PGY1, 8 LYR and 8 experts). Total path length measured with ICSAD and GRS scores were significantly different between all groups, except for LYR compared to experts (p = 0.664 for GRS and p = 0.72 for ICSAD). Regarding jugular CVC procedural time, LYR and experts were faster than PGY1 and MS (p < 0.05). Spearman correlation coefficient was ?0.684 (p < 0.001) between ICSAD and GRS scores.Conclusions
ICSAD is a valid tool for assessment of jugular CVC since it differentiates between expert and novice subjects, and correlates with a validated GRS for jugular CVC in a simulated torso.10.
Objectives
To characterize biomarkers that underlie osteosarcoma (OS) metastasis based on an ego-network.Results
From the microarray data, we obtained 13,326 genes. By combining PPI data and microarray data, 10,520 shared genes were found and constructed into ego-networks. 17 significant ego-networks were identified with p < 0.05. In the pathway enrichment analysis, seven ego-networks were identified with the most significant pathway.Conclusions
These significant ego-modules were potential biomarkers that reveal the potential mechanisms in OS metastasis, which may contribute to understanding cancer prognoses and providing new perspectives in the treatment of cancer.11.
Elif Erdem Ibrahim Inan Harbiyeli Hazal Boral Macit Ilkit Meltem Yagmur Reha Ersoz 《Mycopathologia》2018,183(3):521-527
Purpose
To evaluate the efficiency of corneal collagen cross-linking (CXL) in addition to topical voriconazole in cases with mycotic keratitis.Design
Retrospective case series in a tertiary university hospital.Participants
CXL was performed on 13 patients with mycotic keratitis who presented poor or no response to topical voriconazole treatment.Methods
The clinical features, symptoms, treatment results and complications were recorded retrospectively. The corneal infection was graded according to the depth of infection into the stroma (from grade 1 to grade 3). The visual analogue scale was used to calculate the pain score before and 2 days after surgery.Main Outcome Measures
Grade of the corneal infection.Results
Mean age of 13 patients (6 female and 7 male) was 42.4 ± 17.7 years (20–74 years). Fungus was demonstrated in culture (eight patients) or cytological examination (five patients). Seven of the 13 patients (54%) were healed with topical voriconazole and CXL adjuvant treatment in 26 ± 10 days (15–40 days). The remaining six patients did not respond to CXL treatment; they initially presented with higher grade ulcers. Pre- and post-operative pain score values were 8 ± 0.8 and 3.5 ± 1, respectively (p < 0.05).Conclusions
The current study suggests that adjunctive CXL treatment is effective in patients with small and superficial mycotic ulcers. These observations require further research by large randomized clinical trials.12.
Felipe A. de Oliveira Mohamed H. Shahin Yan Gong Caitrin W. McDonough Amber L. Beitelshees John G. Gums Arlene B. Chapman Eric Boerwinkle Stephen T. Turner Reginald F. Frye Oliver Fiehn Rima Kaddurah-Daouk Julie A. Johnson Rhonda M. Cooper-DeHoff 《Metabolomics : Official journal of the Metabolomic Society》2016,12(8):129
Introduction
While atenolol is an effective antihypertensive agent, its use is also associated with adverse events including hyperglycemia and incident diabetes that may offset the benefits of blood pressure lowering. By combining metabolomic and genomic data acquired from hypertensive individuals treated with atenolol, it may be possible to better understand the pathways that most impact the development of an adverse glycemic state.Objective
To identify biomarkers that can help predict susceptibility to blood glucose excursions during exposure to atenolol.Methods
Plasma samples acquired from 234 Caucasian participants treated with atenolol in the Pharmacogenomic Evaluation of Antihypertensive Responses trial were analyzed by gas chromatography Time-Of-Flight Mass Spectroscopy. Metabolomics and genomics data were integrated by first correlating participant’s metabolomic profiles to change in glucose after treatment with atenolol, and then incorporating genotype information from genes involved in metabolite pathways associated with glucose response.Results
Our findings indicate that the baseline level of β-alanine was associated with glucose change after treatment with atenolol (Q = 0.007, β = 2.97 mg/dL). Analysis of genomic data revealed that carriers of the G allele for SNP rs2669429 in gene DPYS, which codes for dihydropyrimidinase, an enzyme involved in β-alanine formation, had significantly higher glucose levels after treatment with atenolol when compared with non-carriers (Q = 0.05, β = 2.76 mg/dL). This finding was replicated in participants who received atenolol as an add-on therapy (P = 0.04, β = 1.86 mg/dL).Conclusion
These results suggest that β-alanine and rs2669429 may be predictors of atenolol-induced hyperglycemia in Caucasian individuals and further investigation is warranted.13.
Kim B. Pælestik Nichlas R. Jespersen Rebekka V. Jensen Jacob Johnsen Hans Erik Bøtker Steen B. Kristiansen 《Cardiovascular diabetology》2017,16(1):148
Background
Hypoglycemia is associated with increased mortality rate in patients with diabetes. The underlying mechanisms may involve reduced myocardial tolerance to ischemia and reperfusion (IR) or reduced capacity for ischemic preconditioning (IPC). As IPC is associated with increased myocardial glucose uptake (MGU) during reperfusion, cardioprotection is linked to glucose metabolism possibly by O-linked β-N-acetylglucosamine (O-GlcNAc). We aimed to investigate the impact of hypoglycemia in hearts from animals with diabetes on myocardial IR tolerance, on the efficacy of IPC and whether modulations of MGU and O-GlcNAc levels are involved in the underlying mechanisms.Methods
In a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6–7 in each group) infarct size (IS) was evaluated after 40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l]. Myocardial glucose uptake and O-GlcNAc levels were evaluated during reperfusion. IPC was induced by 2 × 5 min of global ischemia prior to index ischemia.Results
IS increased in hearts from animals with (p < 0.01) and without (p < 0.01) diabetes during hypoglycemia compared to normoglycemia. IPC reduced IS during normoglycemia in both animals with (p < 0.01) and without (p < 0.01) diabetes. During hypoglycemia, however, IPC only reduced IS in hearts from animals with diabetes (p < 0.05). IPC increased MGU during reperfusion and O-GlcNAc levels in animals with diabetes during hypo- (MGU: p < 0.05, O-GlcNAc: p < 0.05) and normoglycemia (MGU: p < 0.01, O-GlcNAc: p < 0.05) and in animals without diabetes only during normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01).Conclusions
Hypoglycemia increases myocardial susceptibility to IR injury in hearts from animals with and without diabetes. In contrast to hearts from animals without diabetes, the hearts from animals with diabetes are amenable to cardioprotection during hypoglycemia. In parallel with IPC induced cardioprotection, MGU and O-GlcNAc levels increase suggesting that increased MGU and O-GlcNAc levels are involved in the mechanisms of IPC.14.
Seth D. Rhoades Aalim M. Weljie 《Metabolomics : Official journal of the Metabolomic Society》2016,12(12):183
Introduction
Both reverse-phase and HILIC chemistries are deployed for liquid-chromatography mass spectrometry (LC–MS) metabolomics analyses, however HILIC methods lag behind reverse-phase methods in reproducibility and versatility. Comprehensive metabolomics analysis is additionally complicated by the physiochemical diversity of metabolites and array of tunable analytical parameters.Objective
Our aim was to rationally and efficiently design complementary HILIC-based polar metabolomics methods on multiple instruments using design of experiments (DoE).Methods
We iteratively tuned LC and MS conditions on ion-switching triple quadrupole (QqQ) and quadrupole-time-of-flight (qTOF) mass spectrometers through multiple rounds of a workflow we term Comprehensive optimization of LC–MS metabolomics methods using design of experiments (COLMeD). Multivariate statistical analysis guided our decision process in the method optimizations.Results
LC–MS/MS tuning for the QqQ method on serum metabolites yielded a median response increase of 161.5 % (p < 0.0001) over initial conditions with a 13.3 % increase in metabolite coverage. The COLMeD output was benchmarked against two widely used polar metabolomics methods, demonstrating total ion current increases of 105.8 and 57.3 %, with median metabolite response increases of 106.1 and 10.3 % (p < 0.0001 and p < 0.05 respectively). For our optimized qTOF method, 22 solvent systems were compared on a standard mix of physiochemically diverse metabolites, followed by COLMeD optimization, yielding a median 29.8 % response increase (p < 0.0001) over initial conditions.Conclusions
The COLMeD process elucidated response tradeoffs, facilitating improved chromatography and MS response without compromising separation of isobars. COLMeD is efficient, requiring no more than 20 injections in a given DoE round, and flexible, capable of class-specific optimization as demonstrated through acylcarnitine optimization within the QqQ method.15.
Hai-Ying Zhu Long Jin Qing Guo Zhao-Bo Luo Xiao-Chen Li Yu-Chen Zhang Xiao-Xu Xing Mei-Fu Xuan Guang-Lei Zhang Qi-Rong Luo Jun-Xia Wang Cheng-Du Cui Wen-Xue Li Zheng-Yun Cui Xi-Jun Yin Jin-Dan Kang 《Biotechnology letters》2017,39(5):775-783
Objective
To investigate the effect of the small molecule, RepSox, on the expression of developmentally important genes and the pre-implantation development of rhesus monkey–pig interspecies somatic cell nuclear transfer (iSCNT) embryos.Results
Rhesus monkey cells expressing the monomeric red fluorescent protein 1 which have a normal (42) chromosome complement, were used as donor cells to generate iSCNT embryos. RepSox increased the expression levels of the pluripotency-related genes, Oct4 and Nanog (p < 0.05), but not of Sox2 compared with untreated embryos at the 2–4-cell stage. Expression of the anti-apoptotic gene, Bcl2, and the pro-apoptotic gene Bax was also affected at the 2–4-cell stage. RepSox treatment also increased the immunostaining intensity of Oct4 at the blastocyst stage (p < 0.05). Although the blastocyst developmental rate was higher in the group treated with 25 µM RepSox for 24 h than in the untreated control group (2.4 vs. 1.2%, p > 0.05), this was not significant.Conclusion
RepSox can improve the developmental potential of rhesus monkey–pig iSCNT embryos by regulating the expression of pluripotency-related genes.16.
Fatma Elzahraa Akram Tarek El-Tayeb Khaled Abou-Aisha Mohamed El-Azizi 《Annals of clinical microbiology and antimicrobials》2016,15(1):48
Background
Silver nanoparticles (AgNPs) are potential antimicrobials agents, which can be considered as an alternative to antibiotics for the treatment of infections caused by multi-drug resistant bacteria. The antimicrobial effects of double and triple combinations of AgNPs, visible blue light, and the conventional antibiotics amoxicillin, azithromycin, clarithromycin, linezolid, and vancomycin, against ten clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) were investigated.Methods
The antimicrobial activity of AgNPs, applied in combination with blue light, against selected isolates of MRSA was investigated at 1/2–1/128 of its minimal inhibitory concentration (MIC) in 24-well plates. The wells were exposed to blue light source at 460 nm and 250 mW for 1 h using a photon emitting diode. Samples were taken at different time intervals, and viable bacterial counts were determined. The double combinations of AgNPs and each of the antibiotics were assessed by the checkerboard method. The killing assay was used to test possible synergistic effects when blue light was further combined to AgNPs and each antibiotic at a time against selected isolates of MRSA.Results
The bactericidal activity of AgNPs, at sub-MIC, and blue light was significantly (p < 0.001) enhanced when both agents were applied in combination compared to each agent alone. Similarly, synergistic interactions were observed when AgNPs were combined with amoxicillin, azithromycin, clarithromycin or linezolid in 30–40 % of the double combinations with no observed antagonistic interaction against the tested isolates. Combination of the AgNPs with vancomycin did not result in enhanced killing against all isolates tested. The antimicrobial activity against MRSA isolates was significantly enhanced in triple combinations of AgNPs, blue light and antibiotic, compared to treatments involving one or two agents. The bactericidal activities were highest when azithromycin or clarithromycin was included in the triple therapy compared to the other antibiotics tested.Conclusions
A new strategy can be used to combat serious infections caused by MRSA by combining AgNPs, blue light, and antibiotics. This triple therapy may include antibiotics, which have been proven to be ineffective against MRSA. The suggested approach would be useful to face the fast-growing drug-resistance with the slow development of new antimicrobial agents, and to preserve last resort antibiotics such as vancomycin.17.
Luminita Baditoiu Carmen Axente Diana Lungeanu Delia Muntean Florin Horhat Roxana Moldovan Elena Hogea Ovidiu Bedreag Dorel Sandesc Monica Licker 《Annals of clinical microbiology and antimicrobials》2017,16(1):71
Background
Over recent decades, a dramatic increase in infections caused by multidrug-resistant pathogens has been observed worldwide. The aim of the present study was to investigate the relationship between local resistance bacterial patterns and antibiotic consumption in an intensive care unit in a Romanian university hospital.Methods
A prospective study was conducted between 1st January 2012 and 31st December 2013. Data covering the consumption of antibacterial drugs and the incidence density for the main resistance phenotypes was collected on a monthly basis, and this data was aggregated quarterly. The relationship between the antibiotic consumption and resistance was investigated using cross-correlation, and four regression models were constructed, using the SPSS version 20.0 (IBM, Chicago, IL) and the R version 3.2.3 packages.Results
During the period studied, the incidence of combined-resistant and carbapenem-resistant P. aeruginosa strains increased significantly [(gradient = 0.78, R2 = 0.707, p = 0.009) (gradient = 0.74, R2 = 0.666, p = 0.013) respectively], mirroring the increase in consumption of β-lactam antibiotics with β-lactamase inhibitors (piperacillin/tazobactam) and carbapenems (meropenem) [(gradient = 10.91, R2 = 0.698, p = 0.010) and (gradient = 14.63, R2 = 0.753, p = 0.005) respectively]. The highest cross-correlation coefficients for zero time lags were found between combined-resistant vs. penicillins consumption and carbapenem-resistant P. aeruginosa strains vs. carbapenems consumption (0.876 and 0.928, respectively). The best model describing the relation between combined-resistant P. aeruginosa strains and penicillins consumption during a given quarter incorporates both the consumption and the incidence of combined-resistant strains in the hospital department during the previous quarter (multiple R2 = 0.953, p = 0.017). The best model for explaining the carbapenem resistance of P. aeruginosa strains based on meropenem consumption during a given quarter proved to be the adjusted model which takes into consideration both previous consumption and incidence density of strains during the previous quarter (Multiple R2 = 0.921, p = 0.037).Conclusions
The cross-correlation coefficients and the fitted regression models provide additional evidence that resistance during the a given quarter depends not only on the consumption of antibacterial chemotherapeutic drugs in both that quarter and the previous one, but also on the incidence of resistant strains circulating during the previous quarter.18.
Casey Burton Honglan Shi Yinfa Ma 《Metabolomics : Official journal of the Metabolomic Society》2016,12(5):78
Introduction
Urinary pteridines are putative molecular biomarkers for noninvasive cancer screening and prognostication. Central to their translational biomarker development is the need to understand the sources and extent of their non-epidemiological variation.Objectives
This study was designed to characterize the two primary sources of urinary pteridine variance: daily variation and the effect of dietary folate.Methods
Daily variation was studied by collecting urine specimens (n = 81) three times daily for 3 days. The effect of dietary folate was investigated in a treatment study in which urine specimens (n = 168) were collected daily during a control week and a treatment week during which participants received dietary folate supplements. Measurements of six urinary pteridines were made using high-performance liquid chromatography–tandem mass spectrometry. Coefficients of variation were calculated to characterize daily variance between and within subjects, while nearest neighbor non-parametric analyses were used to identify diurnal patterns and measure dietary folate effects.Results
Daily variance was approximately 35 % RSD for both within-day and between-day periods for most pteridines. Diurnal patterns in response to circadian rhythms were similarly observed for urinary pteridines. Folate supplementation was shown to alter urinary pteridine profiles in a pathway dependent manner, suggesting that dietary folate may regulate endogenous neopterin and biopterin biosynthesis.Conclusions
Urinary pteridine levels were found to be responsive to both daily variation and folate supplementation. These findings provide new insights into pteridine biosynthesis and regulation as well as useful information for the design of future clinical translational research.19.
Radhakrishnan Vishnubalaji Shijun Yue Musaad Alfayez Moustapha Kassem Fei-Fei Liu Abdullah Aldahmash Nehad M. Alajez 《Cancer cell international》2015,16(1):77
Background
Molecular profiling of colorectal cancer (CRC) based on global gene expression has revealed multiple dysregulated signalling pathways associated with drug resistance and poor prognosis. However, the role of BMP2 signaling in CRC is not fully characterised.Methods
Bioinformatics data analysis were conducted on the GSE21510 dataset. Leniviral technology was utilized to stably express BMP2 in the HCT116 CRC model. Gene expression profiling was conducted using Agilent microarray platform while data normalization and bioinformatics were conducted using GeneSpring software. Changes in gene expression were assessed using qRT-PCR. AlamarBlue assay was used to assess cell viability in vitro. In vivo experiments were conducted using SCID mice.Results
Our data revealed frequent downregulation of BMP2 in primary CRC tissues. Additionally, interrogation of publically available gene expression datasets revealed significant downregulation of BMP2 in metastatic recurrent compared to non-metastatic cancer (p = 0.02). Global gene expression analysis in CRC cells over-expressing BMP2 revealed multiple dysregulated pathways mostly affecting cell cycle and DNA damage response. Concordantly, lentiviral-mediated re-expression of BMP2 inhibited HCT116 CRC growth, sphere formation, clonogenic potential, cell migration, and sensitized CRC cells to 5-fluorouracil (5-FU) in vitro. Additionally, BMP2 inhibited CRC tumor formation in SCID mice.Conclusions
Our data revealed an inhibitory role for BMP2 in CRC, suggesting that restoration of BMP2 expression could be a potential therapeutic strategy for CRC.20.