scholarly journals Leukocyte Gene Expression in Patients with Medication Refractory Depression before and after Treatment with ECT or Isoflurane Anesthesia: A Pilot Study

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
E. Iacob ◽  
S. C. Tadler ◽  
K. C. Light ◽  
H. R. Weeks ◽  
K. W. Smith ◽  
...  
Keyword(s):  
Gene Expression ◽  
Healthy Controls ◽  
Open Label ◽  
Blood Samples ◽  
Refractory Depression ◽  
Isoflurane Anesthesia ◽  
Before And After ◽  
Open Label Trial ◽  
Underlying Mechanisms ◽  
Potential Biomarkers

Objective. To evaluate leukocyte gene expression for 9 selected genes (mRNAs) as biological markers in patients with medication refractory depression before and after treatment with ECT or isoflurane anesthesia (ISO).Methods. In a substudy of a nonrandomized open-label trial comparing effects of ECT to ISO therapy, blood samples were obtained before and after treatment from 22 patients with refractory depression, and leukocyte mRNA was assessed by quantitative PCR. Patients’ mRNAs were also compared to 17 healthy controls.Results. Relative to controls, patients before treatment showed significantly higher IL10 and DBI and lower ADRA2A and ASIC3 mRNA (P<0.025). Both ECT and ISO induced significant decreases after treatment in 4 genes: IL10, NR3C1, DRD4, and Sult1A1. After treatment, patients’ DBI, ASIC3, and ADRA2A mRNA remained dysregulated.Conclusion. Significant differences from controls and/or significant changes after ECT or ISO treatment were observed for 7 of the 9 mRNAs studied. Decreased expression of 4 genes after effective treatment with either ECT or ISO suggests possible overlap of underlying mechanisms. Three genes showing dysregulation before and after treatment may be trait-like biomarkers of medication refractory depression. Gene expression for these patients has the potential to facilitate diagnosis, clarify pathophysiology, and identify potential biomarkers for treatment effects.

scholarly journals Bioinformatic analysis identifies potential biomarkers and therapeutic targets of septic-shock-associated acute kidney injury

Hereditas ◽  
2021 ◽  
Vol 158 (1) ◽  
Author(s):  
Yun Tang ◽  
Xiaobo Yang ◽  
Huaqing Shu ◽  
Yuan Yu ◽  
Shangwen Pan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Septic Shock ◽  
Acute Kidney Injury ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Kidney Injury ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Blood Samples ◽  
Potential Biomarkers

Abstract Background Sepsis and septic shock are life-threatening diseases with high mortality rate in intensive care unit (ICU). Acute kidney injury (AKI) is a common complication of sepsis, and its occurrence is a poor prognostic sign to septic patients. We analyzed co-differentially expressed genes (co-DEGs) to explore relationships between septic shock and AKI and reveal potential biomarkers and therapeutic targets of septic-shock-associated AKI (SSAKI). Methods Two gene expression datasets (GSE30718 and GSE57065) were downloaded from the Gene Expression Omnibus (GEO). The GSE57065 dataset included 28 septic shock patients and 25 healthy volunteers and blood samples were collected within 0.5, 24 and 48 h after shock. Specimens of GSE30718 were collected from 26 patients with AKI and 11 control patents. AKI-DEGs and septic-shock-DEGs were identified using the two datasets. Subsequently, Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed to elucidate molecular mechanisms of DEGs. We also evaluated co-DEGs and corresponding predicted miRNAs involved in septic shock and AKI. Results We identified 62 DEGs in AKI specimens and 888, 870, and 717 DEGs in septic shock blood samples within 0.5, 24 and 48 h, respectively. The hub genes of EGF and OLFM4 may be involved in AKI and QPCT, CKAP4, PRKCQ, PLAC8, PRC1, BCL9L, ATP11B, KLHL2, LDLRAP1, NDUFAF1, IFIT2, CSF1R, HGF, NRN1, GZMB, and STAT4 may be associated with septic shock. Besides, co-DEGs of VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 coupled with corresponding predicted miRNAs, especially miR-29b-3p, miR-152-3p, and miR-223-3p may be regarded as promising targets for the diagnosis and treatment of SSAKI in the future. Conclusions Septic shock and AKI are related and VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 genes are significantly associated with novel biomarkers involved in the occurrence and development of SSAKI.

scholarly journals Bioinformatics-Based Identification of lncRNA-miRNA-mRNA Network in Dilated Cardiomyopathy and Drug Prediction

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Wei Liu ◽  
Jinqiang Cai ◽  
Mengjie Tang ◽  
QinJing Yang
Keyword(s):  
Gene Expression ◽  
Dilated Cardiomyopathy ◽  
Protein Interactions ◽  
Unknown Etiology ◽  
Pathway Enrichment Analysis ◽  
Blood Samples ◽  
Qrt Pcr ◽  
Cerna Network ◽  
Potential Biomarkers

Background. Dilated cardiomyopathy (DCM) is a cardiovascular disease of unknown etiology with progressive aggravation. More and more studies have shown that long noncoding RNAs (lncRNAs) play an essential role in dilated cardiomyopathy formation and development. The mechanism of action of competitive endogenous RNA (ceRNA) networks formed based on the principle that lncRNAs affect mRNAs’ expression level by competitively binding microRNAs (miRNAs) in dilated cardiomyopathy has rarely been reported. Objective. This study is aimed at constructing a lncRNA-miRNA-mRNA ceRNA network by bioinformatics analysis methods, discovering, and validating potential biomarkers of DCM in the ceRNA network and determining possible therapeutic targets from them for drug prediction. Methods. A lncRNA dataset and a mRNA microarray dataset were downloaded from the Gene Expression Omnibus Database (GEO). Gene expression was compared between blood samples from patients with dilated cardiomyopathy and blood samples from normal subjects to identify differential expression of lncRNAs and mRNAs. The lncRNA-miRNA-mRNA network was constructed using bioinformatics tools, and functional and pathway enrichment analysis and protein-protein interactions were performed. The mRNAs in the network and the proteins they encode are then used as targets for predicting drugs. Besides, the expression of lncRNAs in the ceRNA network was validated by real-time quantitative PCR (qRT-PCR) experiments in vitro. Results. The differentially expressed lncRNA-miRNA-mRNA ceRNA network in dilated cardiomyopathy was successfully established. Two differentially overexpressed key lncRNAs were found from the network: AC093817 and AC091062, and qRT-PCR experiments further validated the overexpression of AC093817 and AC091062. The mRNAs in the network and the proteins encoded by the mRNAs were used for drug prediction to get related drugs. Conclusion. This study supports a possible mechanism and drug development of dilated cardiomyopathy, AC093817 and AC091062 being potential biomarkers of dilated cardiomyopathy.

An Open Label Trial of Clustered Maintenance rTMS for Patients with Refractory Depression

2013 ◽  
Vol 6 (3) ◽  
pp. 292-297 ◽  
Author(s):  
Paul B. Fitzgerald ◽  
Nicci Grace ◽  
Kate E. Hoy ◽  
Michael Bailey ◽  
Zafiris J. Daskalakis
Keyword(s):  
Open Label ◽  
Refractory Depression ◽  
Open Label Trial

scholarly journals VRK2 gene expression in schizophrenia, bipolar disorder and healthy controls

2016 ◽  
Vol 209 (2) ◽  
pp. 114-120 ◽  
Author(s):  
Martin Tesli ◽  
Katrine Verena Wirgenes ◽  
Timothy Hughes ◽  
Francesco Bettella ◽  
Lavinia Athanasiu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bipolar Disorder ◽  
Association Studies ◽  
Mrna Level ◽  
Genome Wide Association Studies ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Schizophrenia Spectrum Disorders ◽  
Underlying Mechanisms

BackgroundCommon variants in the Vaccinia-related kinase 2 (VRK2) gene have been associated with schizophrenia, but the relevance of its encoded protein VRK2 in the disorder remains unclear.AimsTo identify potential differences in VRK2 gene expression levels between schizophrenia, bipolar disorder, psychosis not otherwise specified (PNOS) and healthy controls.MethodVRK2 mRNA level was measured in whole blood in 652 individuals (schizophrenia, n = 201; bipolar disorder, n = 167; PNOS, n = 61; healthy controls, n = 223), and compared across diagnostic categories and subcategories. Additionally, we analysed for association between 1566 VRK2 single nucleotide polymorphisms and mRNA levels.ResultsWe found lower VRK2 mRNA levels in schizophrenia compared with healthy controls (P<10–12), bipolar disorder (P<10–12) and PNOS (P = 0.0011), and lower levels in PNOS than in healthy controls (P = 0.0042) and bipolar disorder (P = 0.00026). Expression quantitative trait loci in close proximity to the transcription start site of the short isoforms of the VRK2 gene were identified.ConclusionsAltered VRK2 gene expression seems specific for schizophrenia and PNOS, which is in accordance with findings from genome-wide association studies. These results suggest that reduced VRK2 mRNA levels are involved in the underlying mechanisms in schizophrenia spectrum disorders.

scholarly journals The effect of surgery on the levels of matrix metalloproteinases in patients with inguinal hernia

2021 ◽  
Vol 70 (4) ◽  
pp. 627-634
Author(s):  
Sabina Strohalmová ◽  
Kateřina Levová ◽  
Aleš Antonín Kuběna ◽  
Zdeněk Krška ◽  
David Hoskovec ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Inguinal Hernia ◽  
Surgical Treatment ◽  
Matrix Metalloproteinases ◽  
Healthy Controls ◽  
Serum Concentrations ◽  
Blood Samples ◽  
Metalloproteinase Inhibitors ◽  
Before And After ◽  
Circulating Levels

Matrix metalloproteinases (MMPs) are associated with the alteration of extracellular matrix. The purpose of this study was to investigate how the levels of matrix metalloproteinases and their inhibitors – TIMPs are influenced by the presence of inguinal hernia as well as by its surgical treatment. The studied group consisted of 25 patients with inguinal hernia and 21 healthy controls for comparison. Two blood samples - before and after the treatment were collected from patients. Serum concentrations of MMPs and TIMPs were analysed by multiplex immunoassays. There was a difference in circulating levels of MMPs in patients before the surgery compared to healthy controls – the concentrations of MMP-2 and MMP-9 were significantly lower (p=0.026, p=0.018, respectively). After the surgery, the levels of MMPs, especially MMP-2 (p<0.0001), were significantly decreased in patients compared to the preoperative values, apart from MMP 9. On the contrary, MMP-9 showed significant increase after the surgery (p<0.0001). Circulation levels of TIMP-2 in patients were significantly decreased in comparison with controls (p=0.004), whereas levels of TIMP-1 were similar to controls. Both tested metalloproteinase inhibitors showed a significant decrease in detected levels (TIMP-1 p=0.0004; TIMP-2 p<0.0001) after the procedure compared to the preoperative values. The levels of MMPs, especially MMP-2 and MMP-9, and their inhibitors TIMP-1 and TIMP-2 are involved by the presence of inguinal hernia as well as are influenced by the surgery.

scholarly journals Profiling gene expression of the host response to a Plasmodium vivax irradiated sporozoite immunization and infectious challenge

2018 ◽  
Author(s):  
Monica C Rojas-Pena ◽  
Dalia C Arafat ◽  
Juan Manuel Velasquez ◽  
Swetha C Garimalla ◽  
Myriam Arevalo-Herrera ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plasmodium Vivax ◽  
Inflammatory Responses ◽  
Interferon Response ◽  
Global Public Health ◽  
T Cell Signaling ◽  
Blood Samples ◽  
Phase 2 Trial ◽  
Before And After ◽  
Differential Transcription

The development of vaccines that provide sterile protection against human malaria is a major global public health priority requiring a better understanding of the mechanisms involved in natural and vaccine-induced sterile immunity. RNAseq was used to profile gene expression of peripheral blood samples from 12 Duffy positive (Fy+) (Plasmodium vivax susceptible) volunteers enrolled in a phase 2 trial who were vaccinated with radiation attenuated P. vivax sporozoites (RAS; 5 were protected, 7 not) and from 5 Fy- (P. vivax resistant) volunteers exposed to mosquitoes harboring live non-attenuated sporozoites. Blood samples were obtained before and after immunization as well as after controlled infection with live P vivax sporozoites. The most profound changes in gene expression were observed between baseline and post-challenge, with 97 distinct signatures differentiating protected and not protected Fy+ individuals. Differentiation was also observed between Fy- and Fy+ protected individuals, notably with downregulation of multiple inflammatory responses as well as extracellular matrix-related gene activity. Analysis of transcriptional modules shows that both B-cell and T-cell signaling are reduced while cell cycle regulation, interferon response, and other informative signatures are elevated in individuals who are not protected against malaria. An asymptomatic individual had an intermediate profile indicative of differential transcription associated with pathology and symptomology. Systems biology thus provides insight into how whole malaria-attenuated sporozoites prime the immune system to protect against malaria, as well as the transcription responses that are associated with sterile protection.

scholarly journals Neoadjuvant palbociclib on ER+ breast cancer (N007): clinical response and EndoPredict’s value

2018 ◽  
Vol 25 (2) ◽  
pp. 123-130 ◽  
Author(s):  
Louis W C Chow ◽  
Satoshi Morita ◽  
Christopher Y C Chow ◽  
Wai-Kuen Ng ◽  
Masakazu Toi
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Clinical Response ◽  
Pathologic Complete Response ◽  
Prognostic Index ◽  
Complete Response ◽  
Risk Scores ◽  
Open Label ◽  
End Points ◽  
Before And After

The purpose of the study was to test the efficacy of neoadjuvant palbociclib therapy and to evaluate its impact on cell cycle arrest and changes in EndoPredict (EP) scores before and after treatment. Postmenopausal women with histologically proven ER+ve, HER2−ve invasive breast cancer, 2 cm or greater, were enrolled in an open-label, single-arm study. Twenty eligible patients were given letrozole 2.5 mg per day together with palbociclib 125 mg per day for 3 out of 4 weeks in repeated cycles for 16 weeks (4 cycles) before surgery. The primary end points were clinical response rates (cRR) and preoperative endocrine prognostic index (PEPI). The secondary end points were pathologic response and gene expression testing with EP test on collected tumor samples. The following results were obtained. 17 patients showed a clinical response of 50% or more, including 8 complete responses and 9 partial responses. There was significant reduction in area (P < 0.0001) and volume (P = 0.017) of the cancer. Pathologic complete response (pCR) was achieved in one patient; all cancers were downgraded after treatment. Ki67 (P = 0.044) and EP scores (P < 0.0001) were significantly reduced after treatment. Analysis of the relative gene expression levels showed that all proliferative genes, IL6ST and RBBP8 were decreased after palbociclib treatment. 6 patients with intermediate and three patients with high PEPI risk scores were found to have low EPclin scores. All patients with high PEPI relapse risk score had high EPclin score. In conclusion, effective clinical response was demonstrated by neoadjuvant letrozole in combination with palbociclib. Compared with PEPI, EPclin might be a better parameter to estimate prognosis after neoadjuvant therapy.

scholarly journals Gene Expression Signature for Prediction of Golimumab Response in a Phase 2a Open-Label Trial of Patients With Ulcerative Colitis

2018 ◽  
Vol 155 (4) ◽  
pp. 1008-1011.e8 ◽  
Author(s):  
Shannon E. Telesco ◽  
Carrie Brodmerkel ◽  
Hongyan Zhang ◽  
Lilianne (Lee-Lian) Kim ◽  
Jewel Johanns ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Gene Expression Signature ◽  
Open Label ◽  
Expression Signature ◽  
Open Label Trial

scholarly journals Hunger and Satiety Peptides: Is There a Pattern to Classify Patients with Prader-Willi Syndrome?

2021 ◽  
Vol 10 (21) ◽  
pp. 5170
Author(s):  
Marta Bueno ◽  
Ester Boixadera-Planas ◽  
Laura Blanco-Hinojo ◽  
Susanna Esteba-Castillo ◽  
Olga Giménez-Palop ◽  
...  
Keyword(s):  
Cluster Analysis ◽  
Peptide Yy ◽  
Prader Willi Syndrome ◽  
Healthy Controls ◽  
Good Tool ◽  
Before And After ◽  
Hormone Responses ◽  
Glucagon Like Peptide 1 ◽  
Underlying Mechanisms ◽  
Cluster 2

Hyperphagia is one of the main problems of patients with Prader-Willi syndrome (PWS) to cope with everyday life. The underlying mechanisms are not yet well understood. Gut-brain hormones are an interrelated network that may be at least partially involved. We aimed to study the hormonal profile of PWS patients in comparison with obese and healthy controls. Thirty adult PWS patients (15 men; age 27.5 ± 8.02 years; BMI 32.4 ± 8.14 kg/m2), 30 obese and 30 healthy controls were studied before and after eating a hypercaloric liquid diet. Plasma brain-derived neurotrophic factor (BDNF), leptin, total and active ghrelin, peptide YY (PYY), pancreatic polypeptide (PP), Glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and amylin were determined at times 0′, 30′, 60′ and 120′. Cluster analysis was used. When considering all peptides together, two clusters were established according to fasting hormonal standardized concentrations. Cluster 1 encompassed most of obese (25/30) and healthy controls (28/30). By contrast, the majority of patients with PWS were located in Cluster 2 (23/27) and presented a similar fasting profile with hyperghrelinemia, high levels of leptin, PYY, GIP and GLP-1, compared to Cluster 1; that may reflect a dysfunction of these hunger/satiety hormones. When peptide behavior over the time was considered, PP concentrations were not sustained postprandially from 60 min onwards in Cluster 2. BDNF and amylin did not help to differentiate the two clusters. Thus, cluster analysis could be a good tool to distinguish and characterize the differences in hormone responses between PWS and obese or healthy controls.

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