Extracellular vesicles promote silica nanoparticle aggregation that inhibits silica-induced cytotoxicity.

Amorphous silica has been approved as a food and pharmaceutical additive. However, its potential to enhance the carcinogenicity of epithelial cells is incontrovertible. With their expanded surface area per unit mass and distinctive cellular incorporation, nano-sized silica particles (nSPs) exhibit heightened cytotoxicity compared to micrometer-sized counterparts. The precise effect of nSPs on the generation of small extracellular vesicles (sEVs) within endosomes after cellular uptake remains unclear. In the present study, we explored the secretion of sEVs from cells and their functional implications following exposure to nSPs. Our findings demonstrate that nSP50 exposure not only induced epithelial-mesenchymal transition (EMT) but also promoted the maturation of multivesicular endosomes (MVEs) along with the secretion of sEVs in A549 cells. Inhibition of sEV secretion using GW4869 and apoptosis activator 2 exacerbated nSP50-induced EMT, indicating that sEV secretion may suppress EMT. Analysis of the function of sEV in a cell-free system revealed that co-incubation of sEVs with nSP50 led to the formation of micrometer-sized aggregates, which exhibited limited uptake efficiency within A549 cells. These results strongly suggest that the secretion of sEVs plays a protective role against the cytotoxicity attributed to nSP50 exposure.

Spontaneous Remission Without Steroid Therapy in Isolated Cardiac Sarcoidosis with Severe Left Ventricular Systolic Dysfunction.

Spontaneous remission is often observed in extracardiac cases of sarcoidosis, such as skin sarcoidosis. However, for cardiac sarcoidosis (CS), the prognosis is unfavorable. Although corticosteroids are the first-line treatment for CS, data regarding the natural history of isolated CS are limited. We describe a rare case of isolated CS with severe left ventricular systolic dysfunction that improved without steroid therapy.

Safety and potential usefulness of sequential intracoronary acetylcholine and ergonovine administration for spasm provocation testing.

BACKGROUND: Although guidelines recommend intracoronary acetylcholine (ACh) and ergonovine (ER) provocation testing for diagnosis of vasospastic angina, the feasibility and safety of sequential (combined) use of both pharmacological agents during the same catheterization session remain unclear. OBJECTIVES: In this study, we investigated the feasibility and safety of sequential intracoronary ACh and ER administration for coronary spasm provocation testing. METHODS: The study included 235 patients who showed positive results on ACh and ER provocation testing. Initial intracoronary ACh administration was followed by ER administration for left coronary artery (LCA) spasm provocation testing. Subsequently, the right coronary artery (RCA) was subjected to sequential ACh and ER administration for provocation testing. The primary outcome of the study was the safety of sequential intracoronary ACh and ER provocation testing, which was assessed based on a composite of all-cause death, sustained ventricular tachycardia and fibrillation, and cardiogenic shock. RESULTS: Even in patients with negative results on sequential intracoronary ACh and ER provocation testing in the LCA and only ACh administration into the RCA, additional administration of ER into the RCA showed a positive provocation test result in 33 of 235 (14.0%) patients; three (1.3%) patients developed adverse effects (cardiogenic shock occurred in all cases) during LCA provocation testing. We observed no deaths attributable to spasm provocation testing. CONCLUSION: Sequential administration of intracoronary ACh and ER was associated with a relatively low major complication rate and may be safe and potentially useful for diagnosis of vasospastic angina.

Safety and potential usefulness of novel coronary spasm provocation testing protocolCoronary spasm represents a subtype of ischemic heart disease, potentially leading to heart attack. Although guidelines recommend intracoronary administration of different pharmacological agents, acetylcholine (ACh) and ergonovine (ER), for coronary spasm provocation testing, the feasibility and safety of sequential (combined) use of both drugs are unclear. In the present study, we showed that sequential administration of intracoronary ACh and ER was associated with a relatively low major complication rate and may be safe and potentially useful for diagnosis of coronary vasospasm.

Right versus left coronary artery involvement in patients with type A acute aortic dissection.

BACKGROUND: Type A acute aortic dissection (AAD) complicated by coronary malperfusion is a life-threatening disease. In the present study, we compared the clinical characteristics and prognostic impact of treatment strategies including surgical treatment and percutaneous coronary intervention (PCI) in type A AAD patients with RCA and LCA involvement. METHODS: This multicenter registry included 220 patients with type A AAD and either RCA or LCA involvement. Treatment strategies were left to treating physicians. The primary endpoint was in-hospital death. RESULTS: Of 220 patients, 115 (52.3%) and 105 (47.7%) had RCA and LCA involvement. Patients with LCA involvement were more1 likely to present with Killip class IV on admission than those with RCA involvement. Coronary angiography was performed in 52 of 220 (23.6%) patients, among whom 39 (75.0%) underwent subsequent PCI. During the hospitalization, 93 (42.3%) patients died. Patients with LCA involvement had an increased risk of in-hospital mortality compared to those with RCA involvement (54.3% vs. 31.3%, p < 0.001). In patients with RCA involvement, multivariable analysis identified Killip class IV and no surgical treatment as predictors of in-hospital death, while PCI and surgical treatment were indicated as factors associated with lower in-hospital mortality in patients with LCA involvement. CONCLUSIONS: The rates of RCA and LCA involvement were similar in type A AAD. Immediate PCI as a bridge to subsequent surgical treatment might improve survival in patients with type A AAD complicated by coronary malperfusion, especially in those with LCA involvement.

Skin, Liver, and Kidney Interactions Contribute to Skin Dryness in Aging KK-Ay/Tajcl Mice.

Type 2 diabetes is a lifestyle-related disease that affects people worldwide and is especially prevalent in the elderly. Many elderly people with diabetes also complain of dry skin; however, the relationship between aging and dry skin in type 2 diabetes is unknown. The purpose of this study was to examine the interaction between aging and dry skin using the specific pathogen-free KK-Ay/TaJcl type 2 diabetes mouse model. Skin dryness in this model increases with age and was evaluated at 10, 27, 40, and 50 weeks. We observed increased mast cell expression, increased histamine and matrix metalloproteinase-1 levels, and decreased collagen expression in the skin of aging KK-Ay/TaJcl mice. In addition, the increased expression of angiopoietin 2, interleukin-6, tumor necrosis factor-α, and endostatin in the blood indicated kidney damage in this model. Aging KK-Ay/TaJcl mice also showed fatty liver pathology, which led to increased reactive oxygen species in the blood and liver, as well as the increased expression of M1 macrophages in the liver. These results showed that dry skin is associated with skin, kidney, and liver interactions in an aging type 2 diabetes mouse model.

Age­related differences for expression of the nerve­specific proteins after peripheral nerve injury.

The effects of aging on axon regeneration currently remain unclear. In addition, the up-regulated expression of neurotrophic factors that occurs within one week of peripheral nerve injury has been shown to play an important role in the axon regeneration. To investigate the effects of aging on axon regeneration, the expression of nerve-specific proteins immediately after peripheral nerve injury were compared between young and aged mice. A mouse peripheral nerve injury model was prepared using the sciatic nerve compression method. In each group, Luxol fast blue staining and immunofluorescence staining were performed to assess the degree of Wallerian degeneration in the sciatic nerve, and to evaluate the expression of repressor element 1-silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), nerve growth factor (NGF), and semaphorin 3A (Sema3A) in the dorsal root ganglion, respectively. Wallerian degeneration was observed in both young and aged mice after peripheral nerve injury. Significant increases were observed in the expression of REST/NRSF (P<0.0001), NT3 (P=0.0279), and Sema3A (P=0.0175) following peripheral nerve injury in young mice, while that of BDNF (P=0.5583) and NGF (P=0.9769) remained unchanged. On the other hand, no significant differences were noted in the expression of these nerve-specific proteins in aged mice. Based on the results of the present study, compensatory changes induced by peripheral nerve injury were initiated by the up-regulated expression of REST/NRSF in young mice, but not in aged mice.

Relationships of pain-causing substances with dry skin and effects of zaltoprofen on alleviation of symptoms in arthritis model mice.

Purpose: Skin dryness is a symptom of rheumatoid arthritis (RA). However, the mechanisms through which dry skin is induced in RA are unclear. Accordingly, in this study, we characterized substances related to pruritus and pain and then evaluated whether oral administration of zaltoprofen (ZLT) alleviated the symptom of dry skin induced by RA in model mice.Material and Methods: DBA/1JJmsSlc collagen-induced arthritis model mice were treated with ZLT, and transepidermal water loss (TEWL), capacitance, and inflammation-, pruritus-, and pain-related markers were assessed.Results: Our findings demonstrated that arthritis model mice treated with ZLT exhibited suppression of increases in TEWL and decreases in capacitance. Furthermore, ZLT also blocked the increase in mast cell numbers, substance P expression, and cyclo-oxygenase-2 expression in the skin and prevented enhancement of plasma levels of thymic stromal lymphopoietin, tumour necrosis factor-α, interleukin-6, histamine, and bradykinin. No changes in plasma levels of corticosterone or reactive oxygen species or skin levels of glucocorticoid receptor were observed in ZLT-treated arthritis model mice.Conclusions: Overall, these findings suggested that patients with RA may benefit from biopharmacy to alleviate joint symptoms and nonsteroidal anti-inflammatory drugs for pain relief and alleviation of skin symptoms.

Influence of Smoking in the Clinical Outcomes of Distal Radius Fractures.

Introduction There are various studies that reviewed the effect of cigarette smoking in fracture healing process. Nonunion, delayed union, and residual pain are the significant risk factors associated with smoking and fracture healing. Little has been known about the impact of smoking in distal radius fracture healing. We intend to explore in brief the effect of smoking in distal radius fracture healing and comparing it with nonsmokers having the same fracture fixation and analyze the outcomes with respect to fracture healing and return of function. Materials and Methods Of the total 186 patients, 92 were included in the study with ( n = male: 31, female: 61) mean age of 60.2 years. They were divided into two groups: smoking ( n = 43) and nonsmoking ( n = 49). All had surgical fixation of the distal radius with volar locking plate and started on early mobilization. The range of motion of the wrist, grip, visual analog scale, quick disabilities of the arm and shoulder and hand score, Mayo wrist score, and bone healing period were noted between these two groups and compared with statistical analysis. Results The mean follow-up period was 8.7 months. There was a significant association of young age and male patients having distal radius fractures in the smoking group ( p < 0.05). All fractures healed well in both groups without complications. There was no significant difference between these two groups in terms of range of motion, grasp, bone healing period, and functional outcomes. Conclusion Despite the well-known fact that, smoking has negative implications in the fracture healing process, we found group of patients (smoking and nonsmoking) with distal radius fractures treated by volar locking plates healed well with good radiological union and excellent functional outcome There is no significant influence of smoking in distal radius fracture fixation.

Indomethacin, a Non-steroidal Anti-inflammatory Drug, Induces Skin Dryness via PPARγ in Mice.

Cyclooxygenase (COX)-1-selective inhibitors have side effects such as itching and dryness of the skin. In this study, the degree of skin dryness and the onset mechanism of this condition were investigated by comparing the effects of three non-steroidal anti-inflammatory drugs (NSAIDs) in mice. Mice were orally administered either indomethacin, loxoprofen sodium, or celecoxib (n = 5 per group) once daily for four consecutive days, and blood samples as well as skin and jejunal tissues were isolated on day 5. In the mice treated with indomethacin, transepidermal water loss was significantly increased, and dry skin was observed. In addition, the expression of matrix metalloproteinase (MMP)-I, mast cells, CD163, CD23, CD21, histamine, and peroxisome proliferation-activated receptor (PPAR)γ in the skin and jejunum was increased, and the blood levels of interleukin-10 and immunoglobulin E were also increased. In contrast, the expression of collagen type I in the skin was decreased. These results show that indomethacin activates PPARγ in the skin and jejunum, changes the polarity of macrophages, increases the secretion of MMP-1 from mast cells, and decomposes collagen type I, leading to dry skin.

Dual-phase Au-Pt alloys free from magnetic susceptibility artifacts in magnetic resonance imaging.

PURPOSE: Magnetic resonance imaging (MRI) devices are frequently used in image-based diagnosis. In the case of large artifacts, which are generated in magnetic resonance (MR) images when magnetic materials, such as metals, are present in the body, these devices are less useful. This study aimed to develop a dual-phase Au-Pt alloy that does not generate artifacts in MR images and has high workability to prepare medical devices. MATERIALS AND METHODS: A processing method to produce a dual-phase Au-Pt alloy was established, and the magnetic susceptibility and artifacts of different alloy compositions were determined using a SQUID (superconducting quantum interference device) flux meter and a 1.5 T-MRI system. The crystallographic phases of the prepared alloy samples were identified using X-ray diffraction. Sample cross-sections were observed using a metallurgical microscope. Furthermore, a thinning test was conducted to examine alloy workability. RESULTS: Dual-phase Au-Pt alloys Au70Pt30 and Au67Pt33-the former heat-treated at 800 and 850 °C and the latter heat-treated at 900 °C-generated minimal artifacts when imaged in a 1.5 T-MRI system. Their volume magnetic susceptibility increased as the heat-treatment temperature decreased. The alloy surfaces were observed to be uniform. Moreover, the workability of the dual-phase alloy was considerably better than that of the single-phase alloy. CONCLUSION: Volume magnetic susceptibility could be controlled by changing the composition and processing temperature of the Au-Pt alloys. Dual-phase Au-Pt alloys those do not generate magnetic susceptibility artifacts in MRI images and have good workability could be prepared. The alloys are expected to be used in the preparation of various implantable medical devices.

Glycyrrhizin ameliorates melanoma cell extravasation into mouse lungs by regulating signal transduction through HMGB1 and its receptors.

Metastasis, which accounts for the majority of all cancer-related deaths, occurs through several steps, namely, local invasion, intravasation, transport, extravasation, and colonization. Glycyrrhizin has been reported to inhibit pulmonary metastasis in mice inoculated with B16 melanoma. This study aimed to identify the mechanism through which glycyrrhizin ameliorates the extravasation of melanoma cells into mouse lungs. Following B16 melanoma cell injection, mice were orally administered glycyrrhizin once every two days over 2 weeks; lung samples were then obtained and analyzed. Blood samples were collected on the final day, and cytokine plasma levels were determined. We found that glycyrrhizin ameliorated the extravasation of melanoma cells into the lungs and suppressed the plasma levels of interleukin-6, tumor necrosis factor-α, and transforming growth factor-ß. Furthermore, glycyrrhizin ameliorated the lung tissue expression of high mobility group box-1 protein (HMGB1), receptor for advanced glycation end products (RAGE), Toll-like receptor (TLR)-4, RAS, extracellular signal-related kinase, NF-κB, myeloid differentiation primary response 88, IκB kinase complex, epithelial-mesenchymal transition markers, and vascular endothelial growth factor-A. Our study demonstrates that glycyrrhizin ameliorates melanoma metastasis by regulating the HMGB1/RAGE and HMGB1/TLR-4 signal transduction pathways.

Mechanical Properties Enhancement of the Au-Cu-Al Alloys via Phase Constitution Manipulation.

To enhance the mechanical properties (e.g., strength and elongation) of the face-centered cubic (fcc) α-phase in the Au-Cu-Al system, this study focused on the introduction of the martensite phase (doubled B19 (DB19) crystal structure of Au2CuAl) via the manipulation of alloy compositions. Fundamental evaluations, such as microstructure observations, phase identifications, thermal analysis, tensile behavior examinations, and reflectance analysis, have been conducted. The presence of fcc annealing twins was observed in both the optical microscope (OM) and the scanning electron microscope (SEM) images. Both strength and elongation of the alloys were greatly promoted while the DB19 martensite phase was introduced into the alloys. Amongst all the prepared specimens, the 47Au41Cu12Al and the 44Au44Cu12Al alloys performed the optimized mechanical properties. The enhancement of strength and ductility in these two alloys was achieved while the stress plateau was observed during the tensile deformation. A plot of the ultimate tensile strength (UTS) against fracture strain was constructed to illustrate the effects of the introduction of the DB19 martensite phase on the mechanical properties of the alloys. Regardless of the manipulation of the alloy compositions and the introduction of the DB19 martensite phase, the reflectance stayed almost identical to pure Au.

Coexistence of Spontaneous Coronary Artery Dissection, Takotsubo Cardiomyopathy, and Myocardial Bridge.

We report a case of spontaneous coronary artery dissection located next to a myocardial bridge in a patient with concomitant takotsubo cardiomyopathy. A fusion image with multidetector-row computed tomography and single-photon emission computed tomography played an important role in the diagnosis of these lesions. (Level of Difficulty: Advanced.).

[The Mid-term Results of Transapical Transcatheter Aortic Valve Implantation for Aortic Stenosis].

We aimed to evaluate the results of transapical transcatheter aortic valve implantation (TAVI) for aortic stenosis. Thirty patients who had aortic stenosis and underwent transapical TAVI between 2016 and 2020 were enrolled. Medical records were reviewed, and the following data were retrieved and analyzed:basic demographic data, and intraoperative data and postoperative outcomes. Mean age was 85.8 years. There were 3 intraoperative complications (1 apex bleeding, 1 coronary stenosis and 1 mitral regurgitation). Extracorporeal membrane oxygenation was initiated due to unstable hemodynamics in two patients. One patient was converted to mitral valve replacement due to severe mitral regurgitation. There were 2 in-hospital complications (1 with sick sinus syndrome and 1 with cerebral infarction). One patient died of cerebral infarction and eventually, the 30-day mortality was 3%. Median observational period was 1.3 years. Three-year survival was 87.3%. Left ventricular ejection fraction increased by six months after the procedure and then, reached plateau. Left ventricular mass index decreased constantly throughout the observational period. Both parameters at one year after the procedure were significantly higher than preoperative ones. In conclusion, survival after transapical TAVI was favorable because of the low critical complication rate. Both left ventricular functional improvement and reverse remodeling were obtained.

Correction of humpback and DISI deformities by vascularized bone grafting in patients with scaphoid nonunion.

INTRODUCTION: Although vascularized bone grafting (VBG) using 1, 2 intercompartmental supraretinacular artery (1, 2 ICSRA) is effective for scaphoid nonunion, dorsal intercalated segment instability (DISI) deformity persists even after correction of humpback deformity (HD). The purpose of this retrospective study was to evaluate the correction of HD and DISI deformity after 1, 2 ICSRA VBG for scaphoid nonunion. METHODS: We treated 18 patients (mean age: 25.8, 16 males and 2 females) with scaphoid nonunion using a 1, 2-ICSRA VBG between January 2010 and December 2018. The average time from injury to surgery was 20.0 (3-120) months. The nonunions were located at the waist in all patients. The correction of HD and DISI deformity was investigated on the preoperative images and images at the last examination. RESULTS: In all patients, the correction of HD was positively correlated with that of DISI deformity. Moreover, we focused on the time from injury to surgery and evaluated changes in HD and DISI deformity according to the time to surgery. As a result, changes in HD and DISI deformity were positively correlated in patients with a shorter time to surgery but were not correlated when the time to surgery exceeded 5 months. CONCLUSIONS: These results suggest that DISI deformity can be corrected by correcting HD when the time from injury to surgery is short, but that correction is difficult if the time to surgery is prolonged.

Outcomes of conservative treatment for bony mallet fingers.

BACKGROUND: The treatment strategy for bony mallet fingers remains controversial. The outcomes of conservative treatment were investigated in this study. In addition, the time to bone union, and gap between the bone fragment and distal phalanx are discussed. METHODS: The subjects were 26 patients (27 fingers) with bony mallet fingers (20 males and 6 females, mean age: 46.0 years old, the mean limitation of extension of the distal interphalangeal (DIP) joint: - 20.2°). In conservative treatment, splinting was applied for 6 weeks, followed by 2-week taping. The time to bone union, range of motion of the DIP joint, and the Crawford classification on the final follow-up were investigated. In addition, the bone fragment occupation rate was evaluated on plain radiography on the first examination. Furthermore, the gap on the first examination and after splinting. The relationship between the gap and bone union period was also investigated. RESULTS: The mean time from injury to bone union was 170.2 days, the mean range of motion of the DIP joint was - 8.5° in extension and 60.9° in flexion, and the Crawford classification was Excellent for 22 fingers, Good for 2, Fair for 2, and Poor for 1. On the first examination, the mean bone fragment occupation rate was 44.0%. The mean gap on the first examination was 1.1 mm and this was significantly narrowed to 0.8 mm after splinting (p < 0.01). No significant correlation was noted between the time to bone union and gap on the first examination (p = 0.16), however, a significant positive correlation was noted between them after splinting (p < 0.01). CONCLUSIONS: This study suggested that a favorable clinical outcome can be achieved by conservative treatment. Moreover, the bone union period decreased as the gap after splinting decreased, being significantly correlated.