Heat Shot Research Articles

Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation Analysis Reveal Insights into the Molecular Mechanism of Cordia myxa in the Treatment of Liver Cancer.

Traditional treatments of cancer have faced various challenges, including toxicity, medication resistance, and financial burdens. On the other hand, bioactive phytochemicals employed in complementary alternative medicine have recently gained interest due to their ability to control a wide range of molecular pathways while being less harmful. As a result, we used a network pharmacology approach to study the possible regulatory mechanisms of active constituents of Cordia myxa for the treatment of liver cancer (LC). Active constituents were retrieved from the IMPPAT database and the literature review, and their targets were retrieved from the STITCH and Swiss Target Prediction databases. LC-related targets were retrieved from expression datasets (GSE39791, GSE76427, GSE22058, GSE87630, and GSE112790) through gene expression omnibus (GEO). The DAVID Gene Ontology (GO) database was used to annotate target proteins, while the Kyoto Encyclopedia and Genome Database (KEGG) was used to analyze signaling pathway enrichment. STRING and Cytoscape were used to create protein-protein interaction networks (PPI), while the degree scoring algorithm of CytoHubba was used to identify hub genes. The GEPIA2 server was used for survival analysis, and PyRx was used for molecular docking analysis. Survival and network analysis revealed that five genes named heat shot protein 90 AA1 (HSP90AA1), estrogen receptor 1 (ESR1), cytochrome P450 3A4 (CYP3A4), cyclin-dependent kinase 1 (CDK1), and matrix metalloproteinase-9 (MMP9) are linked with the survival of LC patients. Finally, we conclude that four extremely active ingredients, namely cosmosiin, rosmarinic acid, quercetin, and rubinin influence the expression of HSP90AA1, which may serve as a potential therapeutic target for LC. These results were further validated by molecular dynamics simulation analysis, which predicted the complexes with highly stable dynamics. The residues of the targeted protein showed a highly stable nature except for the N-terminal domain without affecting the drug binding. An integrated network pharmacology and docking study demonstrated that C. myxa had a promising preventative effect on LC by working on cancer-related signaling pathways.

Preface: SolarPACES 2022, 28th International Conference on Concentrating Solar Power and Chemical Energy Systems

The SolarPACES 2022 International Conference was held from September 27 to September 30, 2022 in Albuquerque, New Mexico. As the premier international conference and network for advancing commercial deployment and research and development of concentrating solar-thermal power (CSP) and related technologies, the community was excited to convene in person after two years of virtual collaboration. The conference brought together more than 400 participants from 29 countries. The technical presentations and plenary sessions highlighted exciting advances in state-of-the-art commercial deployment and next-generation research and development. There was much focus on emerging commercial markets, including the value of thermal energy storage for cost-effective long duration energy storage – charged either with electricity or solar heat – and the use of solar thermal energy for industrial and chemical processes, especially to decarbonize the large portion of energy that’s currently used for industrial process heating. By holding the conference in the U.S., we were able to highlight particular technical and strategic objectives being advanced by the U.S. Department of Energy (DOE) and the US Government, including the progress in advancing the Generation 3 (Gen3) CSP test facility [1] at Sandia National Laboratories. This megawatt-scale system will demonstrate a fully integrated thermal transport and storage system that can collect, store, and deliver heat above 700° Celsius, using solid particle heat transfer media. Attendees to the conference were able to tour the globally renowned CSP research center at Sandia National Laboratories and the National Solar Thermal Test Facility (NSTTF). The NSTTF opened in 1978 as the world’s first tower research facility for CSP and has been operating for more than 40 years. The site has been a center of excellence in the development of molten salt technologies for CSP and has played a key role in the demonstration of technologies used in some of the largest solar power plants in the world. We also highlighted the recent announcements from the U.S. Department of Energy of the Energy Earthshot Initiatives to accelerate breakthroughs of abundant, affordable, and reliable clean energy solutions by the end of this decade. Specifically, the Long Duration Storage Shot [2] established a target to reduce the cost of grid-scale energy storage by 90% for systems that deliver 10 or more hours of duration, to $0.05 per kilowatt-hour of electricity delivered from storage. The Industrial Heat Shot [3] aims to develop cost-competitive industrial heat decarbonization technologies with at least 85% lower greenhouse gas emissions by 2035. Hydrogen Shot [4] seeks to reduce the cost of clean hydrogen by 80%, to $1 per 1 kilogram. CSP technologies have promising potential to contribute to all of these important goals. The 2022 conference covered important contributions in all of these areas, and more, across 15 technical tracks, coordinated and chaired by international experts in each field. We had high quality contributions across the board, including 211 oral presentations and 111 posters. Additionally, the plenary sessions brought together leading experts on energy storage, US and global markets for CSP technologies, and a specific focus on industrial decarbonization. On behalf of SolarPACES, I thank all of the conference participants, authors, presenters, track chairs, and the conference organizing committee for an extremely successful meeting! Avi Shultz Chairman of the 28th SolarPACES conference

Advanced network pharmacology study reveals multi-pathway and multi-gene regulatory molecular mechanism of Bacopa monnieri in liver cancer based on data mining, molecular modeling, and microarray data analysis

Liver cancer is a malignant tumor that grows on the surface or inside the liver. The leading cause is a viral infection with hepatitis B or C virus. Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer. A list of studies evidences the therapeutic efficacy of Bacopa monnieri against liver cancer, but the precise molecular mechanism is yet to be discovered. This study combines data mining, network pharmacology, and molecular docking analysis to potentially revolutionize liver cancer treatment by identifying effective phytochemicals. Initially, the information on active constituents of B. monnieri and target genes of both liver cancer and B. monnieri were retrieved from literature as well as from publicly available databases. Based on the matching results between B. monnieri potential targets and liver cancer targets, the protein-protein interaction (PPI) network was constructed using the STRING database and imported into Cytoscape for screening of hub genes based on their degree of connectivity. Later, the interactions network between compounds and overlapping genes was constructed using Cytoscape software to analyze the network pharmacological prospective effects of B. monnieri on liver cancer. Gene Ontology (GO) and KEGG pathway analysis of hub genes revealed that these genes are involved in the cancer-related pathway. Lastly, the expression level of core targets was analyzed using microarray data (GSE39791, GSE76427, GSE22058, GSE87630, and GSE112790). Further, the GEPIA server and PyRx software were used for survival and molecular docking analysis, respectively. In summary, we proposed that quercetin, luteolin, apigenin, catechin, epicatechin, stigmasterol, beta-sitosterol, celastrol, and betulic acid inhibit tumor growth by affecting tumor protein 53 (TP53), interleukin 6 (IL6), RAC-alpha serine/threonine protein kinases 1 (AKT1), caspase-3 (CASP3), tumor necrosis factor (TNF), jun proto-oncogene (JUN), heat shot protein 90 AA1 (HSP90AA1), vascular endothelial growth factor A (VEGFA), epidermal growth factor receptor (EGFR), and SRC proto-oncogene (SRC). Through, microarray data analysis, the expression level of JUN and IL6 were found to be upregulated while the expression level of HSP90AA1 was found to be downregulated. Kaplan–Meier survival analysis indicated that HSP90AA1 and JUN are promising candidate genes that can serve as diagnostic and prognostic biomarkers for liver cancer. Moreover, the molecular docking and molecular dynamic simulation of 60ns well complemented the binding affinity of the compound and revealed strong stability of predicted compounds at the docked site. Calculation of binding free energies using MMPBSA and MMGBSA validated the strong binding affinity between the compound and binding pockets of HSP90AA1 and JUN. Despite that, in vivo and in vitro studies are mandatory to unveil pharmacokinetics and biosafety profiles to completely track the candidature status of B. monnieri in liver cancer.

5613423 TREATMENT OF ERYTHROID PRECURSOR CELLS FROM β-THALASSEMIC PATIENTS WITH ISOXAZOLE DERIVATIVES: POTENT INDUCTION OF FETAL HEMOGLOBIN

Background: Increased production of fetal hemoglobin (HbF) can be beneficial for β-thalassemia patients and several clinical trials in β-thalassemia and/or sickle-cell disease (SCD) are ongoing using HbF inducers, such as NCT01245179 (based on the HDAC inhibitor Panobinostat), NCT00790127 (based on 2,2-dimethylbutyrate, HQK-1001) and NCT03877809 (based on the mTOR inhibitor sirolimus). Methods: In this context, new molecules able to induce HbF are needed. In this communication, we have studied in deep a new class of promising HbF inducers characterized by an isoxazole chemical skeleton. These derivatives are 3,4-isoxazolediamide compounds recently synthesized in our laboratories. The original structures of two natural molecules, geldanamycin and radicicol, known to be natural Hsp (Heat Shot Protein) inhibitors, were modified to lead to a novel class of synthetic compounds, containing the isoxazole nucleus, and displaying potent and selective inhibition of Hsp90. Here we used erythroid precursors cells (ErPCs) isolated from β-thalassemic patients and treated with appropriate concentrations of 8 isoxazole derivatives previously demonstrated to be able to induce erythroid differentiation of K562 cells. Results: We demonstrated the high efficacy of the analyzed isoxazoles in inducing HbF. Some derivatives demonstrated an activity even higher than other HbF inducers used as positive controls, such as Hydroxyurea (HU) or Sirolimus. Most of the isoxazole derivatives displayed high effects in decreasing the excess of free α-globin chains in treated ErPCs. All the compounds were assayed for genotoxicity through the Ames test, employing the histidine-requiring Salmonella typhimurium mutant TA 97A, TA98, TA100 and TA1535 strains that allow to check frameshift mutation and base-pair substitution, with and without metabolic activation induced by S9 Mix. These assays excluded any drawbacks related to genotoxicity. Summary - Conclusion: We may therefore conclude that these novel isoxazoles could be proposed for clinical studies for possible therapeutic application for the treatment of β-thalassemia. These compounds have been recently patented as potential therapeutic agents for β-thalassemia (US Patent 11077116). Acknowledgements This study was sustained by the Wellcome Trust (innovator award 208872/Z/17/Z), by AIFA (AIFA-2016-02364887) and by the UE THALAMOSS Project (Thalassemia Modular Stratification System for Personalized Therapy of Βeta-Thalassemia; no. 306201-FP7-HEALTH-2012-INNOVATION-1). We thank A.L.T. (Associazione per la lotta alla Talassemia) “Rino Vullo” - Ferrara, and A.V.L.T. (Associazione Veneta per la Lotta alla Talassemia) “Elio Zago” - APS – Rovigo.

Charge, spin, and heat shot noises in the absence of average currents: Conditions on bounds at zero and finite frequencies

Nonequilibrium situations where selected currents are suppressed are of interest in fields like thermoelectrics and spintronics, raising the question of how the related noises behave. We study such zero-current charge, spin, and heat noises in a two-terminal mesoscopic conductor. In the presence of voltage, spin, and temperature biases, the nonequilibrium (shot) noises of charge, spin, and heat can be arbitrarily large, even if their average currents vanish. However, as soon as a temperature bias is present, additional equilibrium (thermal-like) noise necessarily occurs. We show that this equilibrium noise sets an upper bound on the zero-current charge and spin shot noises, even if additional voltage or spin biases are present. We demonstrate that these bounds can be overcome for heat transport by breaking the spin and electron-hole symmetries, respectively. By contrast, we show that the bound on the charge noise for strictly two-terminal conductors even extends into the finite-frequency regime.

Shot noise of photonic heat transport through an oscillation device modulated by Majorana fermions

The photonic heat transport through an oscillation device under the modulation of Majorana bound states (MBSs) is investigated by using nonequilibrium Green’s function method. The photonic heat current correlation and shot noise formulas are derived. The overall behavior of heat shot noise is governed by terminal temperatures, while its detailed construction is modulated by the attached MBSs and oscillation device. The maximum values of heat current and shot noise are located at integer n times quantum flux Φ0, while they are modulated to zero at half integer of quantum flux (n+12)Φ0 due to changing magnetic flux. The Fano factor presents explicit nonlinear behavior by decreasing firstly to the minimum value and then increasing as the increase of temperature difference. The minimum value of Fano factor is raised up, while its position shifts towards zero temperature difference due to increasing terminal photon frequency. The monotonous enhancement of Fano factor valley is presented due to increasing the coupling constant λ between oscillation device and MBSs, while nonmonotonous variation of Fano factor valley is generated by adjusting the coupling energy ɛM of MBSs.

Evaluation of the effects of interval hypoxic-hyperoxic training in patients with metabolic syndrome

Abstract Introduction Metabolic syndrome (MS) as a “cluster” of interrelated disorders, including insulin resistance, visceral obesity, dyslipidemia, and hypertension, is an serious clinical problem that is a high risk factor for the development of type 2 diabetes, acceleration of the development and progression of cardiovascular diseases, and such increasingly common liver damage like non-alcoholic fatty liver disease. According to a number of authors, metabolic syndrome is a reversible condition, and with early diagnosis and treatment, a reduction in the severity of manifestations of this syndrome can be achieved. A significant role in the treatment of MS and obesity is played by non-drug methods – dosed physical activity, diet, various physiotherapeutic procedures, as well as interval hypoxic-hyperoxic training (IHHT). Objective Evaluation of the effect of interval hypoxic-hyperoxic training (IHHT) on the components of metabolic syndrome, and the possibility of their reversal recovery. Materials and methods The study included 65 patients (33 men) with metabolic syndrome, aged 29–66 years. The patients were divided into 2 groups: study and control (the groups were matched by sex, age, presence of MS components and number of comorbidities). Initially, anthropometric, laboratory and instrumental studies were carried out. The patients of the main group underwent a course of IHHT for 3 weeks, 5 days a week (15 workouts). Patients in the control group underwent a course of training simulating IHHT (placebo), which also consisted of 15 trainings. The duration of one procedure was 40 minutes. Next day after the end of the training course, the changes in all initial parameters were assessed. Results The statistical significance of changes after the IGGT course was assessed using the Wilcoxon test as p<0.05 and was detected in the main group according to the following parameters: reduction in arterial stiffness, measured using CAVI (Cardio-Ankle Vascular Index, on the Fukuda Denshi ap.), a decrease in the stage of liver fibrosis and stiffness of liver tissue (was realized by a non-invasive method, a liver elastometry, on the FibroScan ap. Echosense), a decrease in high-sensitivity C-reactive protein, heat shot protein-70, a decrease in total cholesterol, low density lipoproteins, triglycerides levels. According to nitric oxide, transforming growth factor beta-1, heart-type fatty acid binding protein, there was no significant dynamics after the IHHT course in both groups. There was also a tendency towards a decrease in the indices of the abdominal/hip circumference, weight, and in blood pressure, but this results was not statistically significant, due to the insufficient power of the study (a small number of patients). Conclusions IHHT is a safe, well-tolerated procedure and is recommended in the therapeutic and prophylactic plan for patients with metabolic syndrome, and is effective in correcting and minimizing the components of this syndrome. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): This work was financed by the Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World-Class Research Centers “Digital biodesign and personalized healthcare”

Homology Modeling and Characterization of Novel Stress Inducing Genes and their Split Sites Recognition in the Genome of Zebra Fish (Danio Rario) by Employing Special Consensus Pattern Matching Algorithms- using an in-Silico Method

Zebra fish has long been considered to be as a strong animal model in biology and modern genetics; however now a days its gaining lot of importance in environmental studies as well. The readily availability of entire genome sequences made to permit carrying out in silico studies at Genomic level. As everyone is known that stress is much more complex and complicated process that involves so much of gene regulations known as up regulation and down regulation, the corresponding stress proteins, broadly known as heat shock proteins. In the current study, the potential transcription factor binding sites were traced out by using bioinformatics tools and about 50 heat shock protein genes were predicted by using special alogorithms using pattern matching and position weight matrices. The 3D structure of DNA-binding domain of HSTF-1 ( Heat Shock Transcription factor-1) which is crucial for regulating heat shot proteins was traced out and builted by using homology modelling methods. The 3D structure of the heat shock transcription factor-1 and together with predicted transcription factor binding sites may be validated in future experimental works which would help us in understanding the complex responsive stress mechanisms lying in Zebra fish.

Effect of Mechanical Surface Treatments on Impact Strength for Low Carbon Steel AISI 1020

Objective of this paper is to study the influence of some mechanical surface treatments on impact strength stress for low carbon steel AISI 1020 AISI. Several specimens were subjected or encountered to for impact test were equipped agreeing to ASTM E23 and then were encounter to surface treatment Such as shot peening which was implemented on some specimens using steel balls having diameter of 1.25mm and hardness = 55HRC for (10,20,30) min. Some another’s specimens were treated with using laser peening pulse in notch zone of impact specimen at (5,10,15) laser CO2 pulse. and Plasma also used for surface treatment of impact specimens by using plasma beam for 2,5,10 sec. The results showed that the mechanical surface treatment contributed in improvements of toughness fracture for low carbon steel comparing with base metal. It was found that when increasing shot peening time finding decreasing in the impact strength decreased impact stress because of increase in hardness which generating from heat shot which generated residual stress and the best time was 10 min. and laser pulses and plasma beam were in contributed in increasing impact strength stress for the same reason above and the number of 5 pulse give gave the best result and also the plasma for 5 sec.

Heat and charge transport measurements to access single‐electron quantum characteristics

In the framework of the Floquet scattering‐matrix theory, we discuss how electrical and heat currents accessible in mesoscopics are related to the state of excitations injected by a single‐electron source into an electron waveguide. We put forward an interpretation of a single‐particle heat current, which differs essentially from that of an electrical current. We show that the knowledge of both a time‐dependent electrical current and a time‐dependent heat current allows the full reconstruction of a single‐electron wave function. In addition, we compare electrical and heat shot noise caused by splitting of a regular stream of single‐electron excitations. If only one stream impinges on a wave splitter, the heat shot noise is proportional to the well‐known expression of the charge shot noise, reflecting the partitioning of the incoming single particles. The situation differs when two electronic streams collide at the wave splitter. The shot noise suppression, due to the Pauli exclusion principle, is governed by different overlap integrals in the case of charge and of heat.

Hsp90aa1: a novel target gene of miR-1 in cardiac ischemia/reperfusion injury.

The role of microRNA-1 (miR-1) in ischemia/reperfusion (I/R)-induced injury is not well illustrated. The present study aimed to investigate the expression and potential target of miR-1 in the myocardium of a rat model of I/R. The apoptosis of cardiomyocytes in the ischemic rat myocardium increased on day 1, then attenuated on day 3 and day 7 post-I/R. Heat shot protein 90 (Hsp90) aa1 mRNA expression was decreased post-I/R, and Hsp90aa1 protein level was decreased on day1 post-I/R, but was reversed on day 3 and day 7 post-I/R. MiR-1 was downregulated post-I/R, and repression of miR-1 in cultured neonatal rat ventricular cells (NRVCs) led to an increase of Bcl-2 and decreases of Bax and active caspase-3. Dual luciferase reporter assays revealed that miR-1 interacted with the 310–315 nt site at the 3′UTR of Hsp90aa1, and miR-1 was verified to inhibit Hsp90aa1 expression at the posttranscriptional level. Over-expression of Hsp90aa1 could attenuate oxygen-glucose deprivation (OGD)-induced apoptosis of NRVCs. Additionally, miR-1 mimic, in parallel to Hsp90aa1 siRNA, could enhance OGD-induced apoptosis of NRVCs. Taken together, our results reveal that Hsp90aa1 is a novel target of miR-1, and repression of miR-1 may contribute to the recovery of Hsp90aa1 during myocardial I/R.

Inhibition of Tumor Growth and Alteration of Associated Macrophage Cell Type by an HO-1 Inhibitor in Breast Carcinoma-Bearing Mice

Heme oxygenase-1 [HO-1, also called heat shot protein 32 (HSP32)] can specifically metabolize heme to carbon monoxide, biliverdin, and ferrous iron and plays an important role in the processes of anti-inflammation, tissue protection, and antioxidative stress reaction. It has been reported that HO-1 can promote tumorigenesis and metastasis of many tumors. However, the detailed mechanisms of how HO-1 affects tumor progress are not clear. Here, we used ZnPPIX (a specific inhibitor of HO-1) to evaluate its potential effects on mouse breast cancer and tumor-associated macrophages (TAMs). We found out that mouse 4T1 breast cancer growth can be effectively suppressed through inhibition of HO-1 in vitro and in vivo. Moreover, in the 4T1 mouse model, when HO-1 was suppressed in TAMs, alternatively activated macrophages (M2 type) switched to classically activated macrophages (M1 type). In conclusion, 4T1 breast cancer growth was modulated by HO-1 expression. Furthermore, inhibition of HO-1 may induce tumor-associated immune response by activating TAMs' alternative proliferation. These data suggest that HO-1 may be an important target of breast cancer treatment.