Coexistence of Two Chiral Helices Produces Kink Translation in Spiroplasma Swimming.

The mechanism underlying Spiroplasma swimming is an enigma. This small bacterium possesses two helical shapes with opposite-handedness at a time, and the boundary between them, called a kink, travels down, possibly accompanying the dual rotations of these physically connected helical structures, without any rotary motors such as flagella. Although the outline of dynamics and structural basis has been proposed, the underlying cause to explain the kink translation is missing. We here demonstrated that the cell morphology of Spiroplasma eriocheiris was fixed at the right-handed helix after motility was stopped by the addition of carbonyl cyanide 3-chlorophenylhydrazone (CCCP), and the preferential state was transformed to the other-handedness by the trigger of light irradiation. This process coupled with the generation and propagation of the artificial kink, presumably without any energy input through biological motors. These findings indicate that the coexistence of two chiral helices is sufficient to propagate the kink and thus to propel the cell body.IMPORTANCE Many swimming bacteria generate a propulsion force by rotating helical filaments like a propeller. However, the nonflagellated bacteria Spiroplasma spp. swim without the use of the appendages. The tiny wall-less bacteria possess two chiral helices at a time, and the boundary called a kink travels down, possibly accompanying the dual rotations of the helices. To solve this enigma, we developed an assay to determine the handedness of the body helices at the single-wind level, and demonstrated that the coexistence of body helices triggers the translation of the kink and that the cell body moves by the resultant cell bend propagation. This finding provides us a totally new aspect of bacterial motility, where the body functions as a transformable screw to propel itself forward.

Focal Myocardial Damage in Cardiac Sarcoidosis Characterized by Strain Analysis on Magnetic Resonance Tagged Imaging in Comparison with Fluorodeoxyglucose Positron Emission Tomography Accumulation and Magnetic Resonance Late Gadolinium Enhancement.

OBJECTIVE: The aims of this study were to characterize focal myocardial damage of cardiac sarcoidosis by strain analysis and to compare it with late gadolinium enhancement (LGE) and fluorodeoxyglucose (FDG) positron emission tomography. METHODS: We reviewed 208 segments from 13 cardiac sarcoidosis patients and measured the circumferential strain (Ecc) and the strain change per second (Ecc rate). The mean Ecc and Ecc rate values were compared between the FDG(+) and FDG(-), and the LGE(+) and LGE(-) segments using Welch's t test. RESULTS: The peak and max Ecc rates were better in the LGE(-) segments than in the LGE(+) segments (-11.8 vs -8.9%, 40.5 vs 29.7%/s, both P < 0.001). The max Ecc rate was higher in the FDG(-) segments than in the FDG(+) segments (39.2 vs 31.7%/s, P < 0.001), but the peak Ecc did not differ between the FDG(+) and FDG(-) segments (-11.2 vs -10.1%, P = 0.17). CONCLUSIONS: Strain analysis could reveal focal myocardial damage in the FDG(+) or the LGE(+) segments.

The association between wedging of the aorta and cardiac structural anatomy as revealed using multidetector-row computed tomography.

The aortic root is wedged within the cardiac base. The precise extent of aortic wedging, however, and its influence on the surrounding cardiac structures, has not been systematically investigated. We analysed 100 consecutive patients, who underwent coronary arterial computed tomographic angiography. We assessed the extent of aortic wedging by measuring the vertical distance between the non-adjacent aortic sinus and the inferior epicardium. A shorter distance indicates deeper aortic wedging. We assessed the tilt angle and diameter of the ascending aorta, the relative heights of the left atrial roof and the oval fossa, the shape of the proximal right coronary artery, the angle of the aorta relative to the left ventricular axis, and the lung volume. The mean extent of wedging was 42.7 ± 9.8 mm. Multivariate analysis revealed that ageing, male gender, increased body mass index, patients without cardiomyopathy, the extent of tilting and dilation of the ascending aorta, and lung volume were all independent predictors for deeper aortic wedging (R2  = 0.7400, P < 0.0001). The extent of wedging was additionally correlated with a relatively high left atrial roof (R2  = 0.1394, P < 0.0001) and oval fossa (R2  = 0.1713, P < 0.0001), the shepherd's crook shape of the proximal right coronary artery (R2  = 0.2376, P < 0.0001), and the narrowness of the angulation of the root relative to the left ventricular axis (R2  = 0.2544, P < 0.0001). In conclusion, ageing, male gender, obesity, background cardiac disease, aortic tilting and dilation, and lung volume are all correlated with the extent of wedging of the aortic root within the cardiac base.

Diagnostic Accuracy of Endocardial-to-Epicardial Myocardial Blood Flow Ratio for the Detection of Significant Coronary Artery Disease With Dynamic Myocardial Perfusion Dual-Source Computed Tomography.

BACKGROUND: Previous dynamic stress computed tomography perfusion (CTP) studies used absolute myocardial blood flow (MBF in mL/100 g/min) as a threshold to discriminate flow-limiting coronary artery disease (CAD), but absolute MBF can be vary because of multiple factors. The aim of this study was to compare the diagnostic performance of absolute MBF and the transmural perfusion ratio (TPR) for the detection of flow-limiting CAD, and to clarify the influence of CT delayed enhancement (CTDE) on the diagnostic performance of CTP.Methods and Results:We retrospectively enrolled 51 patients who underwent dual-source CTP and invasive coronary angiography (ICA). TPR was defined as the endocardial MBF of a specific segment divided by the mean of the epicardial MBF of all segments. Flow-limiting CAD was defined as luminal diameter stenosis >90% on ICA or a lesion with fractional flow reserve ≤0.8. Segmental presence and absence of myocardial scar was determined by CTDE. The area under the receiver-operating characteristics curve (AUC) of TPR was significantly greater than that of MBF for the detection of flow-limiting CAD (0.833 vs. 0.711, P=0.0273). Myocardial DE was present in 27 of the 51 patients and in 34 of 143 territories. When only territories containing DE were considered, the AUC of TPR decreased to 0.733. CONCLUSIONS: TPR calculated from absolute MBF demonstrated higher diagnostic performance for the discrimination of flow-limiting CAD when compared with absolute MBF itself.

Slit-Like Deformation of the Coronary Sinus Orifice due to Compression of the Inferior Pyramidal Space by the Severely Dilated Left Ventricle.

The coronary sinus is located within the inferior pyramidal space, which is the part of the epicardial visceral fibroadipose tissue wedging between the four cardiac chambers from the bottom of the heart. Therefore, this region is susceptible to the morphological changes of the cardiac chambers. We present a case of slit-like deformation of the coronary sinus orifice due to compression of the inferior pyramidal space by the severely dilated left ventricle, which has not been previously described.

Clinical cardiac structural anatomy reconstructed within the cardiac contour using multidetector-row computed tomography: Atrial septum and ventricular septum.

Cardiologists are increasingly becoming involved in procedures associated with the atrial septum and ventricular septum, such as transseptal puncture and selective site pacing. Moreover, detailed knowledge about the architecture of the atrial septum and ventricular septum is now available from studies by radiologists and anatomists. However, from the viewpoint of clinical cardiologists, many questions about the three-dimensional cardiac structural anatomy that relate closely to routine invasive procedures remain unresolved. Although modern multidetector-row computed tomography could provide answers, interventional cardiologists might have not considered the potential of this equipment, as only a few have performed studies with both radiological imaging and cadaveric hearts. Detailed knowledge of the three-dimensional fluoroscopic cardiac structural anatomy could help to reduce the need for contrast medium injection and radiation exposure, and to perform safe interventions. In this article, we present a series of cardiac structural images, including images of the atrial septum and ventricular septum, reconstructed in combination with the cardiac contour using multidetector-row computed tomography. We also discuss the clinical implications of the findings on the basis of accumulated insights of research pioneers. We hope that the present images will serve as a bridge between the fields of cardiology, radiology, and anatomy, and encourage cardiologists to integrate their accumulated insights into the three-dimensional clinical images of the living heart.

Clinical cardiac structural anatomy reconstructed within the cardiac contour using multidetector-row computed tomography: The arrangement and location of the cardiac valves.

It is essential for the interventional cardiologist to have in-depth anatomical information about the three-dimensional arrangement and location of the cardiac valves relative to the various projections of the cardiac contour as revealed fluoroscopically. Multidetector-row computed tomography is useful for providing information about the three-dimensional arrangements of each structure. This article presents cardiac structural images, focusing on the arrangement and location of the cardiac valves, which were reconstructed with the cardiac contour and surrounding structures using multidetector-row computed tomography. We discuss the clinical implications of the findings. We hope these images will serve as a bridge between cardiology, radiology, and anatomy, and will prompt scientists in the field of cardiology to integrate their accumulated insights into three-dimensional clinical images of the living heart.

Clinical cardiac structural anatomy reconstructed within the cardiac contour using multidetector-row computed tomography: Left ventricular outflow tract.

The left ventricular outflow tract (LVOT) is a common site of idiopathic ventricular arrhythmia. Many electrocardiographic characteristics for predicting the origin of arrhythmia have been reported, and their prediction rates are clinically acceptable. Because these approaches are inductive, based on QRS-wave morphology during the arrhythmia and endocardial or epicardial pacing, three-dimensional anatomical accuracy in identifying the exact site of the catheter position is essential. However, fluoroscopic recognition and definition of the anatomy around the LVOT can vary among operators, and three-dimensional anatomical recognition within the cardiac contour is difficult because of the morphological complexity of the LVOT. Detailed knowledge about the three-dimensional fluoroscopic cardiac structural anatomy could help to reduce the need for contrast medium injection and radiation exposure, and to perform safe interventions. In this article, we present a series of structural images of the LVOT reconstructed in combination with the cardiac contour using multidetector-row computed tomography. We also discuss the clinical implications of these findings based on the accumulated insights of research pioneers.

Clinical Structural Anatomy of the Inferior Pyramidal Space Reconstructed Within the Cardiac Contour Using Multidetector-Row Computed Tomography.

Although many studies have described the detailed anatomy of the inferior pyramidal space, it may not be easy for cardiologists who have few chances to study cadaveric hearts to understand the correct morphology of the structure. The inferior pyramidal space is the part of extracardiac fibro-adipose tissue wedging between the 4 cardiac chambers from the diaphragmatic surface of the heart. Many cardiologists have interests in pericardial adipose tissue, but the inferior pyramidal space seems to have been neglected. A number of important structures, including the coronary sinus, atrioventricular node, atrioventricular nodal artery, membranous septum, muscular atrioventricular sandwich (previously called the "muscular atrioventricular septum"), atrial septum, ventricular septum, aortic valvar complex, mitral valvar attachment, and tricuspid valvar attachment are associated with the inferior pyramidal space. We previously revealed its 3-dimensional live anatomy using multidetector-row computed tomography. Moreover, the 3-dimensional understanding of the anatomy in association with the cardiac contour is important from the viewpoints of clinical cardiac electrophysiology. The purpose of this article is to demonstrate extended findings regarding the clinical structural anatomy of the inferior pyramidal space, which was reconstructed in combination with the cardiac contour using multidetector-row computed tomography, and discuss the clinical implications of the findings.

Clinical structural anatomy of the inferior pyramidal space reconstructed from the living heart: Three-dimensional visualization using multidetector-row computed tomography.

The inferior pyramidal space (IPS) comprises the epicardial visceral adipose tissue wedged between the bottoms of the four cardiac chambers from the postero-inferior epicardial surface of the heart. Understanding the complex anatomy around the IPS is important for clinical cardiologists. Although leading anatomists and radiologists have clarified the anatomy of the IPS in detail, few studies have demonstrated this anatomy in three dimensions. The aim of this study was to visualize the three-dimensional anatomy of the IPS reconstructed from the living heart using multidetector-row computed tomography. We also developed an original paper model of the IPS to enhance understanding of its intricate structure.

Optimal angulations for obtaining an en face view of each coronary aortic sinus and the interventricular septum: Correlative anatomy around the left ventricular outflow tract.

An optimal image intensifier angulation used for obtaining an en face view of a target structure is important in electrophysiologic procedures performed around each coronary aortic sinus (CAS). However, few studies have revealed the fluoroscopic anatomy of the target area. This study investigated the optimal angulation for each CAS and the interventricular septum (IVS). The study included 102 consecutive patients who underwent computed tomography coronary angiography. The optimal angle for each CAS was determined by rotating the volume-rendered image around the vertical axis. The angle formed between the anteroposterior axis and IVS was measured using the horizontal section. The frontal direction was defined as zero, positive, or negative if the en face view of the target CAS was obtained in the frontal view, left anterior oblique (LAO) direction, or right anterior oblique (RAO) direction, respectively. The optimal angles for the left, right, and non-CASs were 120.3 ± 10.5°, 4.8 ± 16.3°, and -110.0 ± 13.8°, respectively. The IVS angle was 42.6 ± 8.5°. Accordingly, the optimal image intensifier angulations for the left, right, and non-CASs and the IVS were estimated to be RAO 60°, LAO 5°, LAO 70°, and RAO 50°, respectively. The IVS angle was the most common independent predictor of the optimal angle for each CAS. Differences in the optimal angulations for each CAS and the IVS are demonstrated. The biplane angulation needs to be tailored according to the individual patients and target structures for electrophysiologic procedures.

Dose reduction in dynamic CT stress myocardial perfusion imaging: comparison of 80-kV/370-mAs and 100-kV/300-mAs protocols.

OBJECTIVES: To determine the effect of reduced 80-kV tube voltage with increased 370-mAs tube current on radiation dose, image quality and estimated myocardial blood flow (MBF) of dynamic CT stress myocardial perfusion imaging (CTP) in patients with a normal body mass index (BMI) compared with a 100-kV and 300-mAs protocol. METHODS: Thirty patients with a normal BMI (<25 kg/m(2)) with known or suspected coronary artery disease underwent adenosine-stress dual-source dynamic CTP. Patients were randomised to 80-kV/370-mAs (n = 15) or 100-kV/300-mAs (n = 15) imaging. Maximal enhancement and noise of the left ventricular (LV) cavity, contrast-to-noise ratio (CNR) and MBF of the two groups were compared. RESULTS: Imaging with 80-kV/370-mAs instead of 100-kV/300-mAs was associated with 40% lower radiation dose (mean dose-length product, 359 ± 66 vs 628 ± 112 mGy[Symbol: see text]cm; P < 0.001 ) with no significant difference in CNR (34.5 ± 13.4 vs 33.5 ± 10.4; P = 0.81) or MBF in non-ischaemic myocardium (0.95 ± 0.20 vs 0.99 ± 0.25 ml/min/g; P = 0.66). Studies obtained using 80-kV/370-mAs were associated with 30.9% higher maximal enhancement (804 ± 204 vs 614 ± 115 HU; P < 0.005), and 31.2% greater noise (22.7 ± 3.5 vs 17.4 ± 2.6; P < 0.001). CONCLUSIONS: Dynamic CTP using 80-kV/370-mA instead of 100-kV/300-mAs allowed 40% dose reduction without compromising image quality or MBF. Tube voltage of 80-kV should be considered for individuals with a normal BMI. KEY POINTS: • CT stress perfusion imaging (CTP) is increasingly used to assess myocardial function. • Dynamic CTP is feasible at 80-kV in patients with normal BMI. • An 80-kV/370-mAs protocol allows 40% dose reduction compared with 100-kV/300-mAs. • Contrast-to-noise ratio and myocardial blood flow of the two protocols were comparable.

Relationship of decreased accumulation of (99m)Tc-tetrofosmin on myocardial single-photon emission computed tomography images between QRS duration in dilated cardiomyopathy patient with left bundle branch block.

PURPOSE: This study aimed to clarify the relationship between severity of conduction delay in the left ventricle and myocardial uptake of (99m)Tc-tetrofosmin (TF) in dilated cardiomyopathy (DCM) patients with left bundle branch block (LBBB). METHODS AND RESULTS: Thirty-two DCM patients with LBBB underwent electrocardiography and (99m)Tc-TF myocardial single-photon emission computed tomography (SPECT). SPECT images were acquired at 30 min (early images) and 3 h (late images) after injection. We calculated the total defect score (TDS) using a 20-segment model with a 5-point scoring system. The TDS in early and late images was defined as the summed early score (SES) and summed late score (SLS), respectively. On early images, 29 of 32 patients (91%) had decreased tracer uptake in the septum. All patients showed a decreased tracer uptake in the septum on late images. A significant correlation was observed between TDS (both SES and SLS) and QRS duration, with SLS showing an excellent correlation (SES: r = 0.554, P < 0.001; SLS: r = 0.779, P < 0.0001). CONCLUSIONS: These findings suggest that in DCM patients with LBBB, hypoperfusion and myocardial damage in the septum might occur in accordance with an increase in the QRS duration.

Association between the rotation and three-dimensional tortuosity of the proximal ascending aorta.

Age-related morphological changes of the aorta, including dilatation and elongation, have been reported. However, rotation has not been fully investigated. We focused on the rotation of the ascending aorta and investigated its relationship with tortuosity. One hundred and two consecutive patients who underwent computed tomography coronary angiography were studied. The angle at which the en face view of the volume-rendered image of the right coronary aortic sinus (RCS) was obtained without foreshortening was defined as the rotation index. It was defined as zero if the RCS was squarely visible in the frontal view, positive if it rotated clockwise toward the left anterior oblique (LAO) direction, and negative if it rotated counter-clockwise toward the right anterior oblique (RAO) direction. The tortuosity was evaluated by measuring the biplane tilt angles formed between the ascending aorta and the horizontal line. The mean rotation index, posterior tilt angle viewed from the RAO direction (αRAO ), and anterior tilt angle viewed from the LAO direction (αLAO ) were 4.8 ± 16.3, 60.7 ± 7.0°, and 63.6 ± 9.0°, respectively. Although no correlation was observed between the rotation index and the αLAO (ß = -0.0761, P = 0.1651), there was a significant negative correlation between the rotation index and αRAO (ß = -0.1810, P < 0.0001). In multivariate regression analysis, the rotation index was an independent predictor of the αRAO (ß = -0.1274, P = 0.0008). Clockwise rotation of the proximal ascending aorta exacerbates the tortuosity by tilting the aorta toward the posterior direction.

Fat embolism syndrome: A severe case diagnosed early using dual-energy CT and saved with VA-ECMO and inhaled nitric oxide.

Diagnosing FES is difficult and time-consuming, and identify FES as an etiology of right ventricular volume overload for early diagnosis. Because FES is a reversible condition, even severe cases can bse treated if the patient survives the acute phase.

Nattokinase, a Subtilisin-like Alkaline-Serine Protease, Reduces Mutacin Activity by Inactivating the Competence-Stimulating Peptide in Streptococcus mutans.

Streptococcus mutans is a major cariogenic organism because of its ability to form biofilms on tooth surfaces. Bacteriocins produced by S. mutans (known as mutacins) are indirect pathogenic factors that play a role in the persistence of this microbe in the oral environment. Nattokinase, a subtilisin-like alkaline serine protease, potently inhibits biofilm formation without affecting S. mutans growth. However, effective strategies utilizing nattokinase to control mutacin production by S. mutans are lacking. In this study, we evaluated the effect of nattokinase on mutacin activity in 46 strains of S. mutans with different mutacin genotypes isolated from the dental plaques of pediatric patients with caries. Nattokinase reduced the activity of mutacin against oral streptococci at a concentration of 1 mg/mL in all clinical isolates. Furthermore, nattokinase reduced the expression of non-lantibiotic mutacin structural genes (nlmABCD) and inactivated the extracellular competence-stimulating peptide involved in comDE activation, which regulates non-lantibiotic mutacin gene expression. These results suggest that nattokinase may reduce the virulence of S. mutans and could potentially be used as a new caries-preventive agent as an alternative to conventional drug treatments.

Differentiating Macrovascular and Microvascular Ischemia Using Fractal Analysis of Dynamic Myocardial Perfusion Stress-CT.

OBJECTIVES: Fractal analysis of dynamic myocardial stress computed tomography perfusion imaging (4D-CTP) has shown potential to noninvasively differentiate obstructive coronary artery disease (CAD) and coronary microvascular disease (CMD). This study validates fractal analysis of 4D-CTP in a multicenter setting and assesses its diagnostic accuracy in subgroups with ischemia and nonobstructed coronary arteries (INOCA) and with mild to moderate stenosis. MATERIALS AND METHODS: From the AMPLIFiED multicenter trial, patients with suspected or known chronic myocardial ischemia and an indication for invasive coronary angiography were included. Patients underwent dual-source CT angiography, 4D-CTP, and CT delayed-enhancement imaging. Coronary artery disease, CMD, and normal perfusion were defined by a combined reference standard comprising invasive coronary angiography with fractional flow reserve, and absolute or relative CT-derived myocardial blood flow. Nonobstructed coronary arteries were defined as ≤25% stenosis and mild to moderate stenosis as 26%-80%. RESULTS: In 127 patients (27% female), fractal analysis accurately differentiated CAD (n = 61, 23% female), CMD (n = 23, 30% female), and normal perfusion (n = 34, 35% female) with a multiclass area under the receiver operating characteristic curve (AUC) of 0.92 and high agreement (multiclass κ = 0.89). In patients with ischemia (n = 84), fractal analysis detected CAD (n = 61) over CMD (n = 23) with sensitivity of 95%, specificity of 74%, accuracy of 89%, and AUC of 0.83. In patients with nonobstructed coronary arteries (n = 33), INOCA (n = 15) was detected with sensitivity of 100%, specificity of 78%, accuracy of 88%, and AUC of 0.94. In patients with mild to moderate stenosis (n = 27), fractal analysis detected CAD (n = 19) over CMD with sensitivity of 84%, specificity of 100%, accuracy of 89%, and AUC of 0.95. CONCLUSIONS: In this multicenter study, fractal analysis of 4D-CTP accurately differentiated CAD and CMD including subgroups with INOCA and with mild to moderate stenosis.

E2f1-deficient NOD/SCID mice have dry mouth due to a change of acinar/duct structure and the down-regulation of AQP5 in the salivary gland.

Non-obese diabetic (NOD) mice have been used as a model for dry mouth. NOD mice lacking the gene encoding E2f1, a transcription factor, develop hyposalivation more rapidly progressively than control NOD mice. However, the model mice are associated with an underlying disease such as diabetes. We have now established E2f1-deficient NOD/severe combined immunodeficiency disease (NOD/SCID.E2f1(-/-)) mice to avoid the development of diabetes (Matsui-Inohara et al., Exp Biol Med (Maywood) 234(12):1525-1536, 2009). In this study, we investigated the pathophysiological features of dry mouth using NOD/SCID.E2f1(-/-) mice. In NOD/SCID.E2f1(-/-) mice, the volume of secreted saliva stimulated with pilocarpine is about one third that of control NOD/SCID mice. In behavioral analysis, NOD/SCID.E2f1(-/-) mice drank plenty of water when they ate dry food, and the frequency and time of water intake were almost double compared with control NOD/SCID mice. Histological analysis of submandibular glands with hematoxylin-eosin stain revealed that NOD/SCID.E2f1(-/-) mice have more ducts than NOD/SCID mice. In western blot analysis, the expression of aquaporin 5 (AQP5), a marker of acinar cells, in parotid and in submandibular glands of NOD/SCID.E2f1(-/-) mice was lower than in NOD/SCID mice. Immunohistochemical analysis of parotid and submandibular acini revealed that the localization of AQP5 in NOD/SCID.E2f1(-/-) mice differs from that in NOD/SCID mice; AQP5 was leaky and diffusively localized from the apical membrane to the cytosol in NOD/SCID.E2f1(-/-) mice. The ubiquitination of AQP5 was detected in submandibular glands of NOD/SCID.E2f1(-/-) mice. These findings suggest that the change of acinar/duct structure and the down-regulation of AQP5 in the salivary gland cause the pathogenesis of hyposalivation in NOD/SCID.E2f1(-/-) mice.

Iron oxide nanozymes stabilize stannous fluoride for targeted biofilm killing and synergistic oral disease prevention.

Dental caries (tooth decay) is the most prevalent human disease caused by oral biofilms, affecting nearly half of the global population despite increased use of fluoride, the mainstay anticaries (tooth-enamel protective) agent. Recently, an FDA-approved iron oxide nanozyme formulation (ferumoxytol, Fer) has been shown to disrupt caries-causing biofilms with high specificity via catalytic activation of hydrogen peroxide, but it is incapable of interfering with enamel acid demineralization. Here, we find notable synergy when Fer is combined with stannous fluoride (SnF 2 ), markedly inhibiting both biofilm accumulation and enamel damage more effectively than either alone. Unexpectedly, our data show that SnF 2 enhances the catalytic activity of Fer, significantly increasing reactive oxygen species (ROS) generation and antibiofilm activity. We discover that the stability of SnF 2 (unstable in water) is markedly enhanced when mixed with Fer in aqueous solutions without any additives. Further analyses reveal that Sn 2+ is bound by carboxylate groups in the carboxymethyl-dextran coating of Fer, thus stabilizing SnF 2 and boosting the catalytic activity. Notably, Fer in combination with SnF 2 is exceptionally effective in controlling dental caries in vivo , preventing enamel demineralization and cavitation altogether without adverse effects on the host tissues or causing changes in the oral microbiome diversity. The efficacy of SnF 2 is also enhanced when combined with Fer, showing comparable therapeutic effects at four times lower fluoride concentration. Enamel ultrastructure examination shows that fluoride, iron, and tin are detected in the outer layers of the enamel forming a polyion-rich film, indicating co-delivery onto the tooth surface. Overall, our results reveal a unique therapeutic synergism using approved agents that target complementary biological and physicochemical traits, while providing facile SnF 2 stabilization, to prevent a widespread oral disease more effectively with reduced fluoride exposure.

Iron oxide nanozymes stabilize stannous fluoride for targeted biofilm killing and synergistic oral disease prevention.

Dental caries is the most common human disease caused by oral biofilms despite the widespread use of fluoride as the primary anticaries agent. Recently, an FDA-approved iron oxide nanoparticle (ferumoxytol, Fer) has shown to kill and degrade caries-causing biofilms through catalytic activation of hydrogen peroxide. However, Fer cannot interfere with enamel acid demineralization. Here, we show notable synergy when Fer is combined with stannous fluoride (SnF2), markedly inhibiting both biofilm accumulation and enamel damage more effectively than either alone. Unexpectedly, we discover that the stability of SnF2 is enhanced when mixed with Fer in aqueous solutions while increasing catalytic activity of Fer without any additives. Notably, Fer in combination with SnF2 is exceptionally effective in controlling dental caries in vivo, even at four times lower concentrations, without adverse effects on host tissues or oral microbiome. Our results reveal a potent therapeutic synergism using approved agents while providing facile SnF2 stabilization, to prevent a widespread oral disease with reduced fluoride exposure.