scholarly journals Chondroitin sulfate degradation and eicosanoid metabolism pathways are impaired in focal segmental glomerulosclerosis: Experimental confirmation of an in silico prediction

Bioimpacts ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 89-95
Author(s):  
Shiva Kalantari ◽  
Mohammad Naji ◽  
Mohsen Nafar ◽  
Hootan Yazdani-Kachooei ◽  
Nasrin Borumandnia ◽  
...  
Keyword(s):  
Chondroitin Sulfate ◽  
Focal Segmental Glomerulosclerosis ◽  
In Silico ◽  
Target Genes ◽  
In Silico Analysis ◽  
Non Invasive ◽  
Segmental Glomerulosclerosis ◽  
Eicosanoid Metabolism ◽  
Cox 2 ◽  
Primary Glomerular Disease

Introduction: Focal segmental glomerulosclerosis (FSGS), the most common primary glomerular disease, is a diverse clinical entity that occurs after podocyte injury. Although numerous studies have suggested molecular pathways responsible for the development of FSGS, many still remain unknown about its pathogenic mechanisms. Two important pathways were predicted as candidates for the pathogenesis of FSGS in our previous in silico analysis, whom we aim to confirm experimentally in the present study. Methods: The expression levels of 4 enzyme genes that are representative of "chondroitin sulfate degradation" and "eicosanoid metabolism" pathways were investigated in the urinary sediments of biopsy-proven FSGS patients and healthy subjects using real-time polymerase chain reaction (RT-PCR). These target genes were arylsulfatase, hexosaminidase, cyclooxygenase-2 (COX-2), and prostaglandin I2 synthase. The patients were sub-divided into 2 groups based on the range of proteinuria and glomerular filtration rate and were compared for variation in the expression of target genes. Correlation of target genes with clinical and pathological characteristics of the disease was calculated and receiver operating characteristic (ROC) analysis was performed. Results: A combined panel of arylsulfatase, hexosaminidase, and COX-2 improved the diagnosis of FSGS by 76%. Hexosaminidase was correlated with the level of proteinuria, while COX-2 was correlated with interstitial inflammation and serum creatinine level in the disease group. Conclusion: Our data supported the implication of these target genes and pathways in the pathogenesis of FSGS. In addition, these genes can be considered as non-invasive biomarkers for FSGS.

scholarly journals FRUITFULL Is a Repressor of Apical Hook Opening in Arabidopsis thaliana

2020 ◽  
Vol 21 (17) ◽  
pp. 6438
Author(s):  
Miriam Führer ◽  
Angelika Gaidora ◽  
Peter Venhuizen ◽  
Jedrzej Dobrogojski ◽  
Chloé Béziat ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
In Silico ◽  
Target Genes ◽  
Growth Promotion ◽  
In Silico Analysis ◽  
Regulatory Elements ◽  
Suitable Model ◽  
Differential Growth ◽  
Apical Hook ◽  
Growth Transitions

Plants adjust their architecture to a constantly changing environment, requiring adaptation of differential growth. Despite their importance, molecular switches, which define growth transitions, are largely unknown. Apical hook development in dark grown Arabidopsis thaliana (A. thaliana) seedlings serves as a suitable model for differential growth transition in plants. Here, we show that the phytohormone auxin counteracts the light-induced growth transition during apical hook opening. We, subsequently, identified genes which are inversely regulated by light and auxin. We used in silico analysis of the regulatory elements in this set of genes and subsequently used natural variation in gene expression to uncover correlations between underlying transcription factors and the in silico predicted target genes. This approach uncovered that MADS box transcription factor AGAMOUS-LIKE 8 (AGL8)/FRUITFULL (FUL) modulates apical hook opening. Our data shows that transient FUL expression represses the expression of growth stimulating genes during early phases of apical hook development and therewith guards the transition to growth promotion for apical hook opening. Here, we propose a role for FUL in setting tissue identity, thereby regulating differential growth during apical hook development.

The Role of Micrornas in Regulating Redox Modulation in Bipolar Disorder

2017 ◽  
Vol 41 (S1) ◽  
pp. S119-S119
Author(s):  
H. Kim ◽  
K. Tyryshkin ◽  
N. Elmi ◽  
V. Oliviera ◽  
A. Andreazza ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Transcription Factors ◽  
In Silico ◽  
Target Genes ◽  
In Silico Analysis ◽  
Machine Learning Algorithms ◽  
Validation Dataset ◽  
Control Group ◽  
Redox Modulation ◽  
Validation Experiment

IntroductionAlterations in redox modulation are consistently reported in bipolar disorder (BD). MicroRNAs are targeted regulators of gene expression.Objectives and aimsWe aimed to examine if microRNAs that target redox modulators can discriminate between BD and healthy controls.MethodsData from brains of individuals with and without BD were obtained from Array Collection datasets. MicroRNAs targeting redox modulators were assessed for their ability to discriminate BD from the control group using machine-learning algorithms. Methylation of microRNAs, expression of their transcription factors and redox targets were assessed with ANCOVA with FDR correction. For validation, we acquired plasma samples belonging to 2 families of individuals with and without BD (n = 9). Plasma microRNAs were sequenced using the Ion Total RNA Sequencing Kit (Thermo Fisher Scientific), and microRNAs identified from the in silico analysis were examined in the validation dataset.ResultsWe identified 5 miRNAs (hsa-miR-299, hsa-miR-125a, hsa-miR-145, hsa-miR-30b, hsa-miR424) that were common in two of the four in silico datasets. Target genes glutathione peroxidase 4, ATP5A1, ATP5G1, NDUFS1, NDUFC2, and catalase were expressed at different levels between BD and the control group. Furthermore, our results showed that transcription factors CTCF and USF1 might control the expression of hsa-miR-145, while methylation differences were not found. Finally, hsa-miR-30b was significantly increased in the plasma of patients with BD compared to controls in the validation experiment.ConclusionsOur study demonstrates that microRNAs may have an important role in the initiation of redox changes in BD.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals MicroRNAs Modulate the Pathogenesis of Alzheimer’s Disease: An In Silico Analysis in the Human Brain

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 983
Author(s):  
Agnese Gugliandolo ◽  
Luigi Chiricosta ◽  
Virginia Boccardi ◽  
Patrizia Mecocci ◽  
Placido Bramanti ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nervous System ◽  
In Silico ◽  
Target Genes ◽  
Amyloid Β ◽  
In Silico Analysis ◽  
Protein Translation ◽  
Mirnas Expression ◽  
Silico Analysis

MicroRNAs (miRNAs) are small RNAs involved in the post-transcriptional regulation of their target genes, causing a decrease in protein translation from the mRNA. Different miRNAs are found in the nervous system, where they are involved in its physiological functions, but altered miRNAs expression was also reported in neurodegenerative disorders, including Alzheimer’s disease (AD). AD is characterized by memory loss, cognitive function abnormalities, and various neuropsychiatric disturbances. AD hallmarks are amyloid β (Aβ) aggregates, called senile plaques, and neurofibrillary tangles (NFTs) formed by hyperphosphorylated Tau protein. In this study, we performed an in silico analysis to evaluate altered patterns of miRNAs expression in the brains of AD patients compared to healthy subjects. We found 12 miRNAs that were differentially expressed in AD compared to healthy individuals. These miRNAs have target genes involved in AD pathogenesis. In particular, some miRNAs influence Aβ production, having as target secretase and amyloid precursor protein (APP). Some miRNAs were reported to be involved in nervous system functions, and their alteration can cause neuronal dysfunction.

scholarly journals In silico analysis of active compounds from ethanol extract of Curcuma xanthorrhiza on COX-2 receptors as anti-inflammation candidate

2021 ◽  
Author(s):  
Herawati Herawati ◽  
Yudit Oktanella ◽  
Agri Kaltaria Anisa ◽  
Dyah Kinasih Wuragil ◽  
Aulanni'am Aulanni'am
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Ethanol Extract ◽  
Active Compounds ◽  
Curcuma Xanthorrhiza ◽  
Cox 2 ◽  
Silico Analysis ◽  
Anti Inflammation

scholarly journals Sintesis Senyawa Vanilil Metil Keton dan Uji Aktivitas Antiinflamasi terhadap Enzim COX-1 dan COX-2 melalui Analisis In Silico

ALCHEMY ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 1-11
Author(s):  
Khoirotul Ummah ◽  
Robby Gus Mahardika ◽  
Ana Mardliyah
Keyword(s):  
In Silico ◽  
Methyl Ketone ◽  
Aerobic Condition ◽  
In Silico Analysis ◽  
Inflammatory Activity ◽  
Wacker Oxidation ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Silico Analysis ◽  
Cox 1

This study reports the synthesis of vanillyl methyl ketone from eugenol through Wacker oxidation and anti-inflammatory activity test toward COX-1 and COX-2 through in silico analysis. Wacker oxidation process was catalyzed by PdCl2 and CuCl2 using DMF solvent under the aerobic condition at room temperature for 48 hours. The product of the synthesis was purified by column chromatography and was characterized by NMR, IR, and MS spectroscopy. Characterization by spectroscopic methods showed that vanillyl methyl ketone was formed with a yield of 45% and vanillin (3%) was produced as a by-product. The anti-inflammatory activity of vanillyl methyl ketone was carried out by molecular docking toward   COX-1 and COX-2 obtained from PDB. The analysis showed that the anti-inflammatory activity and selectivity toward COX-2 of vanillyl methyl ketone was higher than eugenol. This was shown by the low binding energy affinity and the number of hydrogen bonds formed between the vanillyl methyl ketone and the active site of the enzyme. Keywords: eugenol, Wacker, vanillyl methyl ketone, antiinflammatory, in silico Pada penelitian ini dilakukan sintesis senyawa vanilil metil keton dari eugenol melalui oksidasi Wacker serta dilakukan uji aktivitas antiinflamasi terhadap enzim COX-1 dan COX-2 melalui analisis in silico. Proses oksidasi Wacker dikatalisis oleh PdCl2 dan CuCl2 menggunakan pelarut DMF dalam kondisi aerob pada suhu ruang selama 48 jam. Senyawa hasil sintesis dipisahkan menggunakan kolom kromatografi dan dikarakterisasi menggunakan spektroskopi NMR, IR dan MS. Hasil karakterisasi menunjukkan bahwa senyawa vanilil metil keton telah terbentuk dengan randemen sebanyak 45% dan juga dihasilkan senyawa vanillin (3%) sebagai produk samping. Aktivitas antiinflamasi senyawa vanilil metil keton dilakukan dengan docking molekuler terhadap enzim COX-1 dan COX-2 yang diperoleh dari PDB. Hasil analisis menunjukkan bahwa aktivitas antiinflamasi dan selektivitas terhadap COX-2 pada senyawa vanilil metil keton lebih tinggi dibandingkan eugenol. Hal ini ditunjukkan melalui rendahnya afinitas energi pengikatan dan banyaknya ikatan hidrogen yang terbentuk antara vanilil metil keton dengan sisi aktif enzim. Kata kunci : eugenol, Wacker, vanilil metil keton, antiinflamasi, in silico

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