Nuclear Cascade Research Articles

High energy neutrino production in gamma-ray bursts: dependence of the neutrino signal on the jet composition

Heavy nuclei can be synthetized or entrained in gamma-ray bursts (GRBs) with implications on the high-energy neutrino emission. By means of a Monte-Carlo algorithm, we model nuclear cascades and investigate their impact on the neutrino production considering kinetic dominated jets (in the internal shock model, including a dissipative photosphere) as well as Poynting flux dominated jets (for a jet model invoking internal-collision-induced magnetic reconnection and turbulence, ICMART). We find that the ICMART model allows for efficient nuclear cascades leading to an overall larger neutrino fluence than in the other two jet models. The survival of nuclei and inefficient nuclear cascades lead to an overall reduction of the neutrino fluence up to one order of magnitude. However, if nuclei are disintegrated, the neutrino fluence may be comparable to the one emitted from a jet loaded with protons. Exploring the parameter space of jet properties, we conclude that the composition and the bulk Lorentz factor have significant impact on the efficiency of nuclear cascades as well as the spectral shape of the expected neutrino fluence. On the other hand, the neutrino spectral distribution is less sensitive to the power-law index of the accelerated population of protons or heavier nuclei. For what concerns the diffuse emission of neutrinos from GRBs, we find that the uncertainty due to the jet composition can be at most comparable to the one related to the GRB cosmological rate.

Nuclear Peace in the Middle East

This paper raises and refutes a number of counterarguments against Saudi nuclearization, and through an argument centred around Waltzian conceptions of neorealism, argues that it could stabilize the Middle East whilst fulfilling KSA’s foreign policy goals in the event Tehran nuclearizes as well. It analyzes key details, such as the effect of nuclearization on the Gulf’s immediate paradigm, the possibility of a nuclear cascade amongst other prominent Islamic nations, as well as the consequences of nuclearization on Saudi-American relations.

Nuclear cascades or more of the same? Why meliorists may have gotten it right: A commentary on Tetlock et al. (2023)

AbstractTetlock et al.'s balanced contribution to the debate over the possibility of long‐range geopolitical forecasting provides a useful roadmap at a critical time. An especially challenging geopolitical juncture compels heightened attention to systematic efforts of this sort that both identify limits on expert judgment and offer ways to overcome them. The task may be extremely difficult‐‐skeptics abound‐‐but is nevertheless vital for a social science true to the mission of enhancing peace and security.This article is protected by copyright. All rights reserved.

Nuclear and electromagnetic cascades induced by ultra-high-energy cosmic rays in radio galaxies: implications for Centaurus A

ABSTRACT Very high energy (VHE) γ-rays ($\gtrsim\!\! 0.1\rm ~TeV$) and neutrinos are crucial for identifying accelerators of ultra-high-energy cosmic rays (UHECRs), but this is challenging especially for UHECR nuclei. In this work, we develop a numerical code to solve the transport equation for UHECRs and their secondaries, where both nuclear and electromagnetic cascades are taken into account self-consistently, considering steady UHECR accelerators such as radio galaxies. In particular, we focus on Centaurus A, which has been proposed as one of the most promising UHECR sources in the local Universe. Motivated by observations of extended VHE γ-ray emission from its kiloparsec-scale jet by the High Energy Stereoscopic System (H.E.S.S.), we study interactions between UHECRs accelerated in the large-scale jet and various target photon fields including blazar-like beamed core emission, and present a quantitative study on VHE γ-ray signatures of UHECR nuclei, including the photodisintegration and Bethe–Heitler pair production processes. We show that VHE γ-rays from UHECR nuclei could be detected by the ground-based γ-ray telescopes given that the dominant composition of UHECRs consists of intermediate-mass (such as oxygen) nuclei.

Numerical analysis method for intra-stage non-equilibrium two-phase condensing flow in wet steam turbine and its application

To improve the numerical calculation performance of the intra-stage wet steam non-equilibrium condensing flow in a wet steam turbine, this paper proposed a numerically modified wet steam non-equilibrium condensation (NEC) model by considering the interphase heat and mass transfer in the Euler/Euler coordinate system. The model was developed based on nucleation kinetics, and the expressions of the critical droplet formation free energy and the nucleation rate were given. First, combining the experimental data, the non-isothermal effect nucleation model was modified by the surface tension coefficient method. Then, the low-pressure modified droplet growth model, which is suitable for describing any range of Knudsen numbers, was employed to calculate the droplet surface heat and mass transfer process, and the steam/liquid two-phase control equations and the turbulence model were presented. Meanwhile, the parameter transfer and coupling problem between the vapor and liquid phases was solved. Subsequently, the modified model and the original model were adopted to solve the wet steam condensing flow at the 1D Moses-Stein nozzle numerically, and the results showed that the modified model could calculate the distribution characteristics of pressure and droplet radius more accurately and fit the experimental results better. Afterward, the characteristicsof the non-equilibrium condensing flow of wet steam in the steam turbine cascade were investigated. Finally, combined with the experimental result on the pressure distribution in the steam turbine plane static cascade, the validity of the proposed numerically modified model was further verified, which provided a theoretical basis for the high-accuracy numerical analysis of the condensing flow in the nuclear power wet steam turbine cascade.

Collimator design for gamma-ray cascade angular correlations in medical imaging

In recent decades, Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) have become workhorses of molecular imaging. The main drawback of these modalities is that they resort to statistical methods of image reconstruction, as the location of the individual nuclei emitting radiation is not accessible. To remedy this situation, we embarked on a project to introduce a new modality of nuclear medical imaging which exploits the non-collinear angular correlations of nuclear gamma-ray cascades subsequent to beta decays. This modality, if effective, determines the location of each decay nucleus. We have retrofitted the small animal PET assembly of RIKEN-Kobe (Japan) with tungsten+PLA (polylactic acid) collimators. The chosen material is inexpensive, amenable to three-dimensional (3D) printing, and has good photon attenuation properties. We included the collimator geometry in GATE (Geant4 Application for Tomographic Emission) simulations and developed algorithms for image reconstruction with medical isotope candidates viz., 111In and 43K. Our preliminary simulations show that data acquisition with a 2 MBq source for 900 s is sufficient to reproduce the source geometry with high resolution. This report summarizes our progress to date and the plans for the near future.

Macrophages facilitate tumor cell PD-L1 expression via an IL-1β-centered loop to attenuate immune checkpoint blockade.

Tumor-associated macrophages (TAMs) play critical roles in reprogramming other immune cells and orchestrating antitumor immunity. However, the interplay between TAMs and tumor cells responsible for enhancing immune evasion remains insufficiently understood. Here, we revealed that interleukin (IL)-1β was among the most abundant cytokines within the in vitro tumor-macrophage coculture system, and enhanced IL-1β expression was associated with impaired cytotoxicity of CD8+ T cells in human ovarian cancer, indicating the possibility that IL-1β mediated immunosuppression during tumor-TAMs crosstalk. Mechanistically, we demonstrated that IL-1β significantly boosted programmed death-ligand 1 (PD-L1) expression in tumor cells via the activation of the nuclear factor-κb signaling cascade. Specifically, IL-1β released from TAMs was triggered by lactate, the anaerobic metabolite of tumor cells, in an inflammasome activation-dependent manner. IL-1β sustained and intensified immunosuppression by promoting C-C motif chemokine ligand 2 secretion in tumor cells to fuel TAMs recruitment. Importantly, IL-1β neutralizing antibody significantly curbed tumor growth and displayed synergistic antitumor efficacies with anti-PD-L1 antibody in tumor-bearing mouse models. Together, this study presents an IL-1β-centered immunosuppressive loop between TAMs and tumor cells, highlighting IL-1β as a candidate therapeutic target to reverse immunosuppression and potentiate immune checkpoint blockade.

Insulin-like growth factor II receptor alpha overexpression in heart aggravates hyperglycemia-induced cardiac inflammation and myocardial necrosis.

Diabetes-induced cardiovascular complications are mainly associated with high morbidity and mortality in patients with diabetes. Insulin-like growth factor II receptor α (IGF-IIRα) is a cardiac risk factor. In this study, we hypothesized IGF-IIRα could also deteriorate diabetic heart injury. The results presented that both in vivo transgenic Sprague-Dawley rat model with specific IGF-IIRα overexpression in the heart and in vitro myocardium H9c2 cells were used to investigate the negative function of IGF-IIRα in diabetic hearts. The results showed that IGF-IIRα overexpression aided hyperglycemia in creating more myocardial injury. Pro-inflammatory factors, such as Tumor necrosis factor-alpha, Interleukin-6, Cyclooxygenase-2, Inducible nitric oxide synthase, and Nuclear factor-kappaB inflammatory cascade, are enhanced in the diabetic myocardium with cardiac-specific IGF-IIRα overexpression. Correspondingly, IGF-IIRα overexpression in the diabetic myocardium also reduced the PI3K-AKT survival axis and activated mitochondrial-dependent apoptosis. Finally, both ejection fraction and fractional shortening were be significantly decrease in diabetic rats with cardiac-specific IGF-IIRα overexpression. Overall, all results provid clear evidence that IGF-IIRα can enhance cardiac damage and is a harmful factor to the heart under high-blood glucose conditions. However, the pathophysiology of IGF-IIRα under different stresses and its downstream regulation in the heart still require further research.

Magnesium yields opposite effects on the nuclear and cytosolic cascades of apoptosis in different rat brain regions.

Magnesium is considered as potential neuroprotective and therapeutic agent, but certain studies have provided evidence of its apoptotic effectiveness in neurons. We aimed to evaluate the possible apoptotic effects of long-term magnesium use in healthy adult rat brains. Magnesium citrate and magnesium glycinate compounds were administered orally to rats for 8 weeks (36 mg/kg). Expression levels of Bcl-2, Bax and Cyt-C genes were analyzed by real-time polymerase chain reactions (RT-PCR) in the prefrontal cortex, hippocampus and striatum regions. Bcl-2, Bax and CytC protein levels were measured using ELISA kits. Tissue sections were evaluated histopathologically with hematoxylin-eosin staining. Compared to the control group, the magnesium-administered groups indicated gene expression reductions in almost all brain regions; pro-apoptotic Bax, anti-apoptotic Bcl-2 and Cyt-C gene expression levels were reduced. With magnesium, the Bcl-2 and Bax protein levels were increased. Bax/Bcl-2 gene and protein ratio were also increased in the striatum and hippocampus, whereas Cyt-C protein levels were decreased or did not change in the magnesium treated groups. There was no pathological finding in histological evaluation. Long-term magnesium usage can promote apoptotic cascade in brain tissue by increasing Bax/Bcl-2 ratio. Cyt-C, a prominent factor processing caspase pathway, was decreased or unchanged. In addition, taking into account the histological evaluation, we supposed that the absence of Cyt-C in the cytosol can prevent the subsequent apoptotic pathway. Consequently, we obtained the findings of apoptotic initiation with magnesium in brain, but this cascade seems to be arrested at later stages.

Malting barley carbon dots-mediated oxidative stress promotes insulin resistance in mice via NF-κB pathway and MAPK cascade

BackgroundFood-borne carbon dots (CDs) are widely generated during food processing and are inevitably ingested by humans causing toxicity. However, the toxic effects of food-borne CDs on the blood glucose metabolism are unknown.ResultsIn this study, we brewed beer via a representative strategy and extracted the melting-barley CDs (MBCDs) to explore the toxic effects on blood glucose in mice. We found the accumulation of fluorescent labeled MBCDs in various organs and oral administration of MBCDs can cause visceral toxicity, manifested as liver damage. Mice were orally administered MBCDs (5 and 25 mg/kg) for 16 weeks, and increased levels of fasting blood glucose were observed in both MBCDs-treated groups. Transcriptomic analyses revealed that MBCDs activate oxidative stress, inflammatory responses, the MAPK cascade, and PI3K/Akt signaling in mice livers. Mechanistically, MBCDs exposure-induced reactive oxygen species (ROS) overproduction activates the nuclear factor-κB (NF-κB) signaling pathway and MAPK cascade, thereby promoting phosphorylated insulin receptor substrate (IRS)-1 at Ser307 and inducing insulin resistance (IR). Meanwhile, the IR promoted gluconeogenesis, which enhanced MBCDs-induced hyperglycemia of mice. Importantly, inhibition of the ROS significantly attenuated the MBCDs-induced inflammatory response and MAPK cascade, thereby alleviating IR and hyperglycemia in mice.ConclusionIn summary, this study revealed that MBCDs promote ROS overproduction and thus induced IR, resulting in imbalance of glucose homeostasis in mice. More importantly, this study was further assessed to reveal an imperative emphasis on the reevaluation of dietary and environmental CDs exposure, and has important implications for T2DM prevention research.Graphical

Global Maps of Galactic Cosmic Ray Induced Ionization at Different Altitudes in Planetary Atmosphere

High-energy precipitating particles of cosmic origin viz. cosmic ray protons of heavier nuclei of galactic and/or solar origin induce complicated nuclear electromagnetic-lepton cascades in the Earth’s atmosphere, eventually leading to an ionization of the ambient air. The induced by cosmic rays atmospheric ionization is related to possible effect of precipitating particles on atmospheric chemistry and physics. In this work, using a combination of state of the art 3-D full target models we computed as realistically as possible, explicitly considering the contribution of heavy ions, the ion production at eight altitudes in the Earth’s atmosphere, scilicet: 25 g/cm2 (≈ 45 km asl), 50 g/cm2 (≈ 35 km asl) Fig. 1, 100 g/cm2 (≈ 24.5 km asl), 150 g/cm2 (≈ 19.5 km asl) Fig. 2, 200 g/cm2 (≈ 16 km asl), 250 g/cm2 (≈ 13.5 km asl) Fig. 3, 300 g/cm2 (≈ 11.5 km asl), 400 g/cm2 (≈ 8.5 km asl) Fig. 4. This includes altitudes from the upper troposphere to the stratosphere. Here we provided global maps with resolution of 1◦×1◦ of the computed ion production rates. Hence, the presented here results give a good basis for further studies related to the space weather and the possible impact of precipitating highenergy particles of galactic and/or solar origin on the atmospheric chemistry and physics.

Pathfinder for a high statistics search for missing energy in gamma cascades

We investigate the feasibility of a high statistics experiment to search for invisible decay modes in nuclear gamma cascades using 200 kg of %36 Cs(Tl) scintillators that are presently available at Texas A\&M. The experiment aims to search for missing energy by robustly establishing the absence of a photon in a well identified gamma cascade. We report on the experimental demonstration of the energy resolution necessary for this search. Prior explorations of this detector concept focused on baryonically coupled physics that could be emitted in $E_2$ transitions. We point out that this protocol can also search for particles that are coupled to photons by searching for the conversion of a photon produced in a gamma cascade into a hidden particle. Examples of these processes include the oscillation of a photon into a hidden photon and the conversion of a photon into an axion-like-particle either in the presence of a magnetic field or via the Primakoff process. This proof-of-concept apparatus appears to have the ability to search for hitherto unconstrained baryonically coupled scalars and pseudoscalars produced in $E_0$ and $M_0$ transitions. If successfully implemented, this experiment serves as a pathfinder for a larger detector with greater containment that can thoroughly probe the existence of new particles with mass below 4 MeV that lie in the poorly constrained supernova ``trapping window'' that exists between 100 keV and 30 MeV.

New Potential of Roxatidine Acetate Hydrochloride on Atopic Dermatitis Mouse Model, Human Keratinocytes, and Human Skin Equivalent Model.

Atopic dermatitis (AD) is a complex inflammatory skin disorder, characterized by a complicated pathophysiology and a wide range of clinical phenotypes. Roxatidine acetate chloride (RXA) is a precursor of Roxatidine and a histamine H2 receptor antagonist, used for the treatment of gastric ulcers. In this study, we aimed to examine whether RXA had anti-AD effects and determine the underlying molecular mechanism of RXA. The anti-AD effects were examined in Dermatophagoides farinae body (Dfb)-induced AD mouse model, tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated HaCaT keratinocytes, and human skin equivalent model using ELISA, histological analysis, immunohistochemistry, Western blot, and immunofluorescence. Results showed that RXA treatment significantly alleviated Dfb-induced AD skin symptoms and clinical severity in mice by decreasing the levels of immunoglobulin E, histamine, and inflammatory cytokines. RXA effectively inhibited the expression of adhesive molecules and recovered the filaggrin expression in Dfb-induced AD skin lesions and TNF-α/IFN-γ-stimulated HaCaT keratinocytes. Additionally, RXA significantly upregulated the expression of aryl hydrocarbon receptor and sirtuin1. The anti-AD effects of RXA were associated with suppressed nuclear factor kappa cascade. Overall, our results suggest that RXA may be a potential anti-AD candidate owing to its inhibitory effect against skin inflammation and protection of the skin barrier function in AD.

Immunization With RANKL Inhibits Osteolytic Bone Metastasis in Breast Cancer.

Breast cancer cells often metastasize to bone. Accumulating evidence suggests that inhibiting the receptor activator of nuclear factor-κB ligand (RANKL) not only leads to reduced bone metastasis of breast cancer but also has antitumoral effects. Here, we used mutant receptor activator of nuclear factor-κB ligand (RANKLM) as a vaccine for active immunization to induce antibodies for immunotherapy of bone metastatic cancer. We investigated whether anti-RANKL antibodies inhibit osteolytic bone metastasis in vitro and in a murine model. MC3T3 cells stimulated by MDA-MB-231 culture medium secreted growth differentiation factor-15 (GDF-15), which induced the nuclear factor-κB signaling cascade. In addition, RANKLM treatment-induced reduction of intraosseous growth of MDA-MB-231 cells correlated with decreased GDF-15 expression, a reduced number of osteolytic lesions, and slower tumor progression. In addition, vaccination with RANKLM led to significant improvement in overall survival and skeletal metastasis in tumor-bearing mice. Induction of anti-RANKL antibodies by RANKLM decreased GDF-15 production by deactivating nuclear factor-κB signaling, which in turn inhibited metastasis of MDA-MB-231 cells to bone. Taken together, the results demonstrate a role for RANKLM immunization in preventing bone metastasis of breast cancer.

Euryfuranyl compounds from edible species of cuttlefish as potential anti-inflammatory leads attenuating NF-κB signaling cascade in lipopolysaccharide-activated macrophages

Nuclear factor-kappa B is an inducible transcription element, which was considered as an important regulator of immune functions, and plays a critical role to induce inflammatory reactions. In this study, we have demonstrated the anti-inflammatory potentials of previously undescribed (4 → 13)-abeo-euryfuranyls (1–2) from the spineless cuttlefish Sepiella inermis in lipopolysaccharide-stimulated macrophages. The euryfuranyl bearing (4 → 13)-abeo-euryfuranyl-2-ene-6-hydroxymethyl-propanoate framework (compound 1) displayed prominent inhibitory effects against pro-inflammatory cyclooxygenase-2 (IC50 0.36 mM) and 5-lipoxygenase (IC50 0.70 mM). Additionally, it suppressed the generation of inducible nitric oxide synthase along with cyclooxygenase-2 and 5-lipoxygenase in lipopolysaccharide-stimulated macrophages. The euryfuranyl analogue (1) down-regulated the mRNA expression of cyclooxygenase-2 and nuclear factor-κB signaling pathway in lipopolysaccharide-activated macrophage cells by hindering the degradation of inhibitor-κB proteins, and transfer of the subunit NF-κB p65 to the nucleus from the cytosol. These results demonstrated that the euryfuranyl analogue could be explored as a promising anti-inflammatory therapeutic lead attenuating nuclear factor-κB signaling cascade.

Defective FXR-SHP Regulation in Obesity Aberrantly Increases miR-802 Expression, Promoting Insulin Resistance and Fatty Liver.

Aberrantly elevated expression in obesity of microRNAs (miRNAs), including the miRNA miR-802, contributes to obesity-associated metabolic complications, but the mechanisms underlying the elevated expression are unclear. Farnesoid X receptor (FXR), a key regulator of hepatic energy metabolism, has potential for treatment of obesity-related diseases. We examined whether a nuclear receptor cascade involving FXR and FXR-induced small heterodimer partner (SHP) regulates expression of miR-802 to maintain glucose and lipid homeostasis. Hepatic miR-802 levels are increased in FXR-knockout (KO) or SHP-KO mice and are decreased by activation of FXR in a SHP-dependent manner. Mechanistically, transactivation of miR-802 by aromatic hydrocarbon receptor (AHR) is inhibited by SHP. In obese mice, activation of FXR by obeticholic acid treatment reduced miR-802 levels and improved insulin resistance and hepatosteatosis, but these beneficial effects were largely abolished by overexpression of miR-802. In patients with nonalcoholic fatty liver disease (NAFLD) and in obese mice, occupancy of SHP is reduced and that of AHR is modestly increased at the miR-802 promoter, consistent with elevated hepatic miR-802 expression. These results demonstrate that normal inhibition of miR-802 by FXR-SHP is defective in obesity, resulting in increased miR-802 levels, insulin resistance, and fatty liver. This FXR-SHP-miR-802 pathway may present novel targets for treating type 2 diabetes and NAFLD.

Attenuation of Hadronic Cascades in Ionization Calorimeter and Long-Range Component

The propagation and detection of electron–nuclear cascades in an ionization calorimeter are considered, and it is shown that the attenuation length associated with ionization may differ strongly from the attenuation length for the energy flux. A possible reason for the hypothesis of a long-range component in detecting cores of extensive air showers is proposed.

Dynamics of Nuclear Cascades in the Photoproduction of Light Neutral Mesons

New experimental data on the multifragmentation of carbon nuclei that is initiated by the photoproduction of neutral pions and eta mesons are discussed. The novelty is associated with the exclusive character of the processes being studied, in which case a determination of partial meson-photoproduction reactions is followed by an analysis of complementary particles for coincidence. The experiment being discussed was performed by the GRAAL (GRenoble Accelerateur Anneau Laser) Collaboration in a beam of 500- to 1500-MeV Compton photons. The possibility of performing new experiments within the BGO-OD Collaboration (Bonn, Germany) is considered. A new method for studying the interaction of short-lived mesons with nuclei on the basis of detecting cascade recoil nucleons is proposed.

Polygalactan from bivalve Crassostrea madrasensis attenuates nuclear factor-κB activation and cytokine production in lipopolysaccharide-activated macrophage

A polygalactosamino-glucopyranosyl fucopyranose →4)-β-GlcAp{(3→1)-α-Fucp}-β-GalNAcp-(4,6-SO3−)-(1→ isolated from the bivalve Crassostrea madrasensis exhibited prospective anti-inflammatory activity against cyclooxygenase-2 and 5-lipoxygenase (IC50 < 50 μg mL−1) on lipopolysaccharide-induced macrophages. The polygalactan attenuated inducible nitric oxide synthase (IC50 65.7 μg mL−1) in lipopolysaccharide-prompted inflammation leading to the reduction of pro-inflammatory cytokine nitric oxide (236.2 μg mL−1 lysate), nuclear factor-κB, tumor necrosis factor-α, and interleukins (0.19−0.22 units mg−1 protein at 100 μg mL-1) by inhibiting cyclooxygenase-2. The polygalacatan suppressed the mRNA of nuclear factor-κB and cyclooxygenase-2 in lipopolysaccharide-induced macrophages. Western blot experiment revealed that the polygalactan attenuated the migration of nuclear factor-κB-p65 to the nucleus from cytoplasm, and suppressed the phosphorylation of α-subunit of κB inhibitor. Greater selectivity index of sulfated polygalactan (3.93) towards inducible cyclooxygenase-2 as compared with the anti-inflammatory agent ibuprofen (1.11), and the potential to inhibit nuclear factor-κB cascade to generate chemokine production manifested its utilization in the development of functional food attenuating inflammation-related disorders.

Lipoprotein(a) as Orchestrator of Calcific Aortic Valve Stenosis.

Aortic valve stenosis (AVS) is the most prevalent valvular heart disease in the Western World with exponentially increased incidence with age. If left untreated, the yearly mortality rates increase up to 25%. Currently, no effective pharmacological interventions have been established to treat or prevent AVS. The only treatment modality so far is surgical or transcatheter aortic valve replacement (AVR). Lipoprotein(a) [Lp(a)] has been implicated as a pivotal player in the pathophysiology of calcification of the valves. Patients with elevated levels of Lp(a) have a higher risk of hospitalization or mortality due to the presence of AVS. Multiple studies indicated Lp(a) as a likely causal and independent risk factor for AVS. This review discusses the most important findings and mechanisms related to Lp(a) and AVS in detail. During the progression of AVS, Lp(a) enters the aortic valve tissue at damaged sites of the valves. Subsequently, autotaxin converts lysophosphatidylcholine in lysophosphatidic acid (LysoPA) which in turn acts as a ligand for the LysoPA receptor. This triggers a nuclear factor-κB cascade leading to increased transcripts of interleukin 6, bone morphogenetic protein 2, and runt-related transcription factor 2. This progresses to the actual calcification of the valves through production of alkaline phosphatase and calcium depositions. Furthermore, this review briefly mentions potentially interesting therapies that may play a role in the treatment or prevention of AVS in the near future.