scholarly journals Citrate Synthase and OGDH as Potential Biomarkers of Atherosclerosis under Chronic Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-35
Author(s):  
Ling-bing Meng ◽  
Gai-feng Hu ◽  
Meng-jie Shan ◽  
Yuan-meng Zhang ◽  
Ze-mou Yu ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Chronic Stress ◽  
Target Genes ◽  
Adrenal Glands ◽  
Citrate Synthase ◽  
Spline Interpolation ◽  
Docking Study ◽  
Control Group ◽  
Molecular Docking Study ◽  
Hub Proteins

Background. Pathological changes of the adrenal gland and the possible underlying molecular mechanisms are currently unclear in the case of atherosclerosis (AS) combined with chronic stress (CS). Methods. New Zealand white rabbits were used to construct a CS and AS animal model. Proteomics and bioinformatics were employed to identify hub proteins in the adrenal gland related to CS and AS. Hub proteins were detected using immunohistochemistry, immunofluorescence assays, and Western blotting. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to analyze the expression of genes. In addition, a neural network model was constructed. The quantitative relationships were inferred by cubic spline interpolation. Enzymatic activity of mitochondrial citrate synthase and OGDH was detected by the enzymatic assay kit. Function of citrate synthase and OGDH with knockdown experiments in the adrenal cell lines was performed. Furthermore, target genes-TF-miRNA regulatory network was constructed. Coimmunoprecipitation (IP) assay and molecular docking study were used to detect the interaction between citrate synthase and OGDH. Results. Two most significant hub proteins (citrate synthase and OGDH) that were related to CS and AS were identified in the adrenal gland using numerous bioinformatic methods. The hub proteins were mainly enriched in mitochondrial proton transport ATP synthase complex, ATPase activation, and the AMPK signaling pathway. Compared with the control group, the adrenal glands were larger and more disordered, irregular, and necrotic in the AS+CS group. The expression of citrate synthase and OGDH was higher in the AS+CS group than in the control group, both at the protein and mRNA levels ( P < 0.05 ). There were strong correlations among the cross-sectional areas of adrenal glands, citrate synthase, and OGDH ( P < 0.05 ) via Spearman’s rho analysis, receiver operating characteristic curves, a neural network model, and cubic spline interpolation. Enzymatic activity of citrate synthase and OGDH increased under the situation of atherosclerosis and chronic stress. Through the CCK8 assay, the adrenal cell viability was downregulated significantly after the knockdown experiment of citrate synthase and OGDH. Target genes-TF-miRNA regulatory network presented the close interrelations among the predicted microRNA, citrate synthase and OGDH. After Coimmunoprecipitation (IP) assay, the result manifested that the citrate synthase and OGDH were coexpressed in the adrenal gland. The molecular docking study showed that the docking score of optimal complex conformation between citrate synthase and OGDH was -6.15 kcal/mol. Conclusion. AS combined with CS plays a significant role on the hypothalamic–pituitary–adrenal (HPA) axis, promotes adrenomegaly, increases the release of glucocorticoid (GC), and might enhance ATP synthesis and energy metabolism in the body through citrate synthase and OGDH gene targets, providing a potential research direction for future related explorations into this mechanism.

scholarly journals EFFECT OF MOBILE PHONE RADIATION ON ADRENAL GLAND OF MALE ALBINO RATS

2020 ◽  
Vol 28 (1) ◽  
Author(s):  
Shalini Gupta ◽  
Shilpi Jain ◽  
Satyam Khare ◽  
Prateek Gautam
Keyword(s):  
Adrenal Gland ◽  
Mobile Phone ◽  
Radiation Exposure ◽  
Mobile Phones ◽  
Adrenal Glands ◽  
Cellular Level ◽  
Control Group ◽  
Albino Rats ◽  
Hormonal Changes ◽  
Mobile Phone Radiation

Introduction: The tremendous growth in telecommunication world has increased the number of mobile phone users to many folds. The benefits of cell phones are just half the picture. The other half may be a darker one. The main aim of this study is to observe the effect of electromagnetic radiation being emitted by mobile phones on adrenal gland microanatomy and the hormones released by the gland on male albino rats. Materials and methods: Forty-two male albino rats of Spargue-Dawley species were divided into two equal groups. The experimental group rats were exposed to mobile phone radiation operating at 900 MHz while the control group rats were not. At the end of every two months, seven rats were sacrificed to analyse histological and hormonal changes. Results: No changes were seen at the cellular level of the adrenal glands even after six months of radiation exposure. Hormonal assay showed a variation in the cortisol levels of the rats but the changes were within normal range. Conclusions: Lack of appreciable changes in the cellular morphology and hormonal levels even after six months of radiation exposure signify that the adrenal glands are not affected by exposure to mobile phones.

A Study on the Effect of High Calorie Diet on Stress Alleviation

2012 ◽  
Vol 724 ◽  
pp. 139-142
Author(s):  
Sang Gyun Roh ◽  
Jae Gook Lee
Keyword(s):  
Food Intake ◽  
Adrenal Gland ◽  
Adrenal Glands ◽  
Feedback Inhibition ◽  
Control Group ◽  
Hormonal Change ◽  
Stress Alleviation ◽  
Calorie Diet ◽  
High Calorie Diet ◽  
High Calorie

In this study, we tried to reveal the presence of a cytokine that is regulated by weight, food intake, body fat, the hypothalamus-pituitary-adrenal axis, and corticosterone. The experiment group was given a high calorie diet and the control group was fed a normal calorie diet, and both groups were exposed to various stresses. The behavioral and hormonal change by the kinds and severity of stresses were measured via their immunologic aspect as well as their stress alleviation by voluntary high calorie food intake. After sacrificing the animal, the adrenal gland fat tissues were weighed, and the high calorie diet group showed heavier adrenal glands than those of the control group. In particular, the CVS A group had lighter adrenal gland weight than the Res B and CVS B groups, and the other groups had heavier adrenal glands. The comparison of plasma ACTH concentration to the corticosteroid secretion ratio showed that the CVS A group had decreased ACTH and an increased corticosteroid/ACTH ratio. This fact shows that the adrenal gland was highly active and, in spite of a normal corticosteroid concentration, induced too much negative feedback inhibition.

scholarly journals Effect of New Thalidomide Analogs in Acute Kidney Injury on Rats

2021 ◽  
Vol 12 (5) ◽  
pp. 6100-6113
Keyword(s):  
Ischemia Reperfusion ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Docking Study ◽  
Positive Control ◽  
Negative Control ◽  
Positive Control Group ◽  
Control Group ◽  
Molecular Docking Study ◽  
The Mean

Renal ischemia/reperfusion (I/R) injury contains multiple mechanisms involving an excessive amount of ROS that causes oxidative stress, inflammation, and rapid kidney dysfunction. This work aimed to study the ability of thalixisostere 3f on angiogenesis and antioxidant effect in I/R. There was a significant decrease in VEGF from thalix and modified thalixisostere 3f groups as compared with that of a negative control group (P < 0.001). There was a significant decrease in the mean concentration of MDA in kidney tissue obtained from thalix and thalixisostere 3f groups as compared with that of a positive control group (P < 0.001). There was a significant increase in the mean concentrations of SOD and GSH in kidney tissue of group's thalix and thalixisostere 3f groups as compared with that of a positive control group. We found that thalixisostere 3f is more effective than thalix in inhibiting the expression VEGF as pro-angiogenic factors. Molecular docking study indicated that the proper recognition of the inhibitor thalix-isostere with the conserved amino acid residues at the binding active site of VEGFR2 as one of the important enzymes to be targeted as part of antiangiogenic anticancer.

scholarly journals Adrenal gland pathology in rats after acute postnatal hypoxia

2013 ◽  
Vol 94 (5) ◽  
pp. 615-621
Author(s):  
G I Gubina-Vakulik ◽  
A V Andreev ◽  
N G Kolousova
Keyword(s):  
Adrenal Gland ◽  
Functional Activity ◽  
Adrenal Glands ◽  
Acute Hypoxia ◽  
Main Group ◽  
Female Rats ◽  
Control Group ◽  
Newborn Rats ◽  
Cambium Layer ◽  
Cellular Regeneration

Aim. To study the histological changes in the adrenal glands of rats with acute postnatal hypoxia and «structural trace» in the adrenal glands during the first month of life. Methods. Wistar rats were used as experimental animals. After calving, the newborn rats (main group, 20 newborn rats, progeny of 5 female rats) were placed in the bell-pressure chamber (simulating altitude of 3.500 meters with an atmospheric pressure of 493 mm Hg) for 5 min. Rats were withdrawn from the experiment by decapitation at the first day (1 hour after the acute postnatal hypoxia modeling, 7 rats), 7 days after (7 rats) and 35 days after (6 rats) the experiment. The same number of intact rats of the control group were examined at the same timepoints. The adrenal glands of rats were examined morphologically using histological, histochemical, immunohistochemical and morphometric methods. Results. It was found that a short episode of mild short hypoxia just after the birth leads to the development of specific adaptive changes in adrenal glands: cortical hyperplasia, increased morpho-functional activity of endocrinocytes in the medullar substance associated with extensive apoptosis, decreasing of morpho-functional activity of endocrinocytes of the glomerular zone and fetal cortex. Cellular regeneration of spongiocytes was observed not only in the cambium layer, but also in the fascicular zone, which presumes not only physiological, but also reparative regeneration. Regeneration of medullar cells, seemingly, only occurs during the first few days after birth by migration of sympathogonia from outside of the adrenal gland to its center. At days 14 th and 35 th, despite the same conditions, histological signs of active functioning of the cortical fascicular zone and medullar substance preserved in animals of the main group compared with the controls. Conclusion. Results of the study prove the need for clinical studies of the adrenal function correction in newborns undergoing postnatal and intranatal acute hypoxia, as well as of consequences for the adrenal gland morpho-functional state after birth for such cases.

EVALUATION OF IN-SILICO ANTICANCER POTENTIAL OF PYRETHROIDS: A COMPARATIVE MOLECULAR DOCKING STUDY

2015 ◽  
Author(s):  
Manik Ghosh ◽  
Kamal Kant ◽  
Anoop Kumar ◽  
Padma Behera ◽  
Naresh Rangra ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Study ◽  
Molecular Docking Study

Myricetin Preferentially Binds to Interfacial Regions in Domains 1 – 3 to Inhibit Cholesterol-Dependent Cytolysins: A Molecular Docking Study

2020 ◽  
Author(s):  
Rafael Espiritu
Keyword(s):  
Molecular Docking ◽  
Structural Changes ◽  
Docking Study ◽  
Listeriolysin O ◽  
Molecular Docking Study ◽  
Docking Analysis ◽  
Streptolysin O ◽  
Molecule Inhibitor ◽  
Human Cd59 ◽  
Anthrolysin O

<p>Cholesterol-dependent cytolysins (CDCs) are proteinaceous toxins secreted as monomers by some Gram-positive and Gram-negative bacteria that contribute to their pathogenicity. These toxins bind to either cholesterol or human CD59, leading to massive structural changes, toxin oligomerization, formation of very large pores, and ultimately cell death, making these proteins promising targets for inhibition. Myricetin, and its related flavonoids, have been previously identified as a candidate small molecule inhibitor of specific CDCs such as listeriolysin O (LLO) and suilysin (SLY), interfering with their oligomerization. In this work, molecular docking was performed to assess the interaction of myricetin with other CDCs whose crystal structures are already known. Results indicated that although myricetin bound to the hitherto identified cavity in domain 4 (D4), much more efficient and stable binding was obtained in sites along the interfacial regions of domains 1 – 3 (D1 – D3). This was common among the tested CDCs, which was primarily due to much more extensive stabilizing intermolecular interactions, as indicated by post-docking analysis. Specifically, myricetin bound to (1) the interface of the three domains in anthrolysin O (ALO), perfringolysin O (PFO), pneumolysin (PLY), SLY, and vaginolysin (VLY), (2) at/near the D1/D3 interface in LLO and streptolysin O (SLO), and (3) along the D2/D3 interface in intermedilysin (ILY). These findings provide theoretical basis on the possibility of using myricetin and its related compounds as a broad-spectrum inhibitor of CDCs to potentially address the diseases associated with these pathogens.</p>

Protective Effect of Hypericum perforatum L. Extract on Hexavalent Chromium Induced Toxicity in Rat Adrenal Gland

2017 ◽  
Vol 68 (9) ◽  
pp. 2014-2017
Author(s):  
Jelena Savici ◽  
Oana Maria Boldura ◽  
Cornel Balta ◽  
Diana Brezovan ◽  
Florin Muselin ◽  
...  
Keyword(s):  
Drinking Water ◽  
Adrenal Gland ◽  
Hexavalent Chromium ◽  
Structural Damage ◽  
Hypericum Perforatum ◽  
Adrenal Glands ◽  
Expression Level ◽  
Apoptotic Pathway ◽  
Hypericum Perforatum L ◽  
Induction Of Apoptosis

This study was carried out to test the possibility of hexavalent chromium administration through drinking water to induce the structural damage in rat�s adrenal glands and the possibility of Hypericum perforatum extract to faith against chromium aggression. Chromium induced cellular stress was determined by the expression level assessment of the Bcl2 genes family, known to modulate the apoptotic pathway. Obtained results showed that exposure to chromium altered adrenal glands morphology, by induction of apoptosis. When Hypericum perforatum extract was administered expression level of Bcl2 genes and histological lesions in adrenal glands were significantly reduced.

Computational Evidences of Phytochemical Mediated Disruption of PLpro Driven Replication of SARS-CoV-2: A Therapeutic Approach Against COVID-19

2020 ◽  
Vol 21 ◽  
Author(s):  
Acharya Balkrishna ◽  
Rashmi Mittal ◽  
Vedpriya Arya
Keyword(s):  
Molecular Docking ◽  
Md Simulation ◽  
Bond Distance ◽  
Immunological Response ◽  
Docking Study ◽  
Receptor Interaction ◽  
Molecular Docking Study ◽  
Replication Process ◽  
Stable Conformation ◽  
Distance Analysis

Background:: COVID-19 caused by SARS-CoV-2 has been declared as global pandemic by WHO. Comprehensive analysis of this unprecedented outbreak may help to fight against the disease and may play a pivotal role in decreasing the mortality rate linked with it. Papain like protease (PLpro), a multifunctional polyprotein facilitates the replication of SARS-CoV-2 and evades it from the host immunological response by antagonizing cytokines, interferons and may be considered as potential drug target to combat the current pandemic. Methods:: Natural moieties obtained from medicinal plants were analysed for their potency to target PLpro of SARS-CoV-2 by molecular docking study and were compared with synthetic analogs named as remdesivir, chloroquine and favipiravir. The stability of complexes of top hits was analysed by MD Simulation and interaction energy was calculated. Furthermore, average RMSD values were computed and deepsite ligand binding pockets were predicted using Play Molecule. Drug like abilities of these moieties were determined using ADMET and bond distance between the ligand and active site was assessed to predict the strength of interaction. Results:: Nimbocinol (-7.6 Kcal/mol) and sage (-7.3 Kcal/mol) exhibited maximum BA against PLpro SARS-CoV-2 as evident from molecular docking study which was found to be even better than remdesivir (-6.1 Kcal/mol), chloroquine (-5.3 Kcal/mol) and favipiravir (-5.7 Kcal/mol). Both nimbocinol-PLpro and sage-PLpro SARS-CoV-2 complex exhibited stable conformation during MD Simulation of 101ns at 310 K and potential, kinetic and electrostatic interaction energies were computed which was observed to be concordant with results of molecular docking study. RMSD average values were found to be 0.496 ± 0.015 Å and 0.598 ± 0.023 Å for nimbocinol and sage respectively thus revealing that both the deviation and fluctuations during MD Simulation were observed to be least. Deepsite prediction disclosed that both compounds occupied cryptic pockets in receptor and non-bond distance analysis revealed the formation of hydrogen bonds during ligand-receptor interaction. ADMET exploration further validated the drug like properties of these compounds. Conclusion:: Present study revealed that active constituents of Azadirachta indica and Salvia officinalis can be potentially used to target SARS-CoV-2 by hindering its replication process.

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