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.

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.

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.

Differences in the mechanism of type 1 and type 2 diabetes-induced skin dryness by using model mice.

Diabetes induces dry skin that may cause infective diseases. In this study, we aimed to clarify the mechanism of diabetes-induced skin dryness in animal models. We also examined the difference in the mechanism of skin dryness in type 1 and type 2 diabetes. We examined skin dryness in type 1 diabetes model mice (streptozotocin [STZ] induction), non-obesity type 2 diabetes model mice (newborn STZ injection), and obesity type 2 diabetes model mice (KK-Ay/TaJcl). An increase in transepidermal water loss was observed in the type 1 diabetes model mice, and reduced skin hydration was observed in the type 2 diabetes model mice. In the type 1 diabetes model mice, an increase in advanced glycation end products and matrix metalloproteinase-9 led to a decline in collagen IV level, inducing skin dryness. In the obesity type 2 diabetes model mice, an increase in the release of histamine and hyaluronidase by mast cells resulted in a decline in the level of hyaluronic acid, inducing skin dryness. However, in the non-obesity type 2 diabetes model mice, the main factors of skin dryness could not be clearly identified. Nevertheless, inflammatory cytokine levels increased. We hypothesize that inflammatory cytokines disrupt the collagen of the skin. Diabetes caused skin dryness in each mouse model, and the mechanism of skin dryness differed by diabetes type.

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.

[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.

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.

Locked wires fixator for fractures of the distal third of the radius and ulna in children.

BACKGROUND: Prevention of redisplacement is an issue after the treatment of fractures of the distal third of the radius in children. In this study, we used a locked wires fixator for this type of fracture and achieved favorable treatment outcomes. METHODS: The subjects were 8 children with fractures of the distal third of the radius (male: 7, female: 1, mean age: 9.0 years old) who underwent surgery with locked wires fixators and were able to be evaluated 12 months after surgery. Immobilization was not applied after surgery. The locked wires fixator or K-wire was removed when the bridging callus was observed on plain radiography 4-6 (mean 5.5) weeks after surgery in all patients. The presence of bone union, functional outcomes, and complications were investigated postoperatively. RESULTS: All patients achieved bone union without redisplacement excellent function. The pin site infection was observed in two patients. CONCLUSIONS: The locked wires fixator may be a new useful treatment method for fractures likely to cause postoperative redisplacement.

Th2 and Th17 Induce Dry Skin in a Mouse Model of Arthritis.

Skin dryness is a characteristic of rheumatoid arthritis (RA) model mice. However, the mechanism underlying the induction of dry skin by RA is unclear. We hypothesized that T helper (Th)2 and Th17 cells mediate this process. A mouse model of DBA/1JJmsSlc collagen-induced arthritis was treated with Th2 or Th17 cell inhibitor, and transepidermal water loss (TEWL) and the expression of markers associated with allergic reaction and inflammation were evaluated. TEWL and plasma levels of thymic stromal lymphopoietin, interleukin (IL)-6 and -17, and tumor necrosis factor (TNF)-α were increased in the arthritis mouse model compared to that in control mice. Administration of Th2 cell inhibitor abolished the increase in TEWL, IL-6, and TNF-α levels, whereas Th17 cell inhibitor reversed TEWL and decreased IL-17 level. Th2 and Th17 cells contribute to the induction of dry skin, but via distinct mechanisms.

Adverse Reaction of Dextran Sodium Sulfate-Induced Colitis in a Collagen-Induced Mouse Arthritis Model.

The pathogenic relationship of ulcerative colitis and rheumatoid arthritis is not known. Therefore, we examined dextran sodium sulfate (DSS)-induced colitis separately and in combination with a mouse arthritis model that mimics rheumatoid arthritis and evaluated the deterioration-related factors of each condition. Arthritis was induced in a collagen-induced arthritis mouse model using DBA/1JJmsSlc mice and ulcerative colitis was induced by the administration of drinking water containing 3.0% (w/v) DSS. The arthritis/DSS-treated mice developed worse colitis scores compared to that of the other groups of mice. The arthritis/DSS-treated mice did not demonstrate changes in hind foot volumes or in the concentration of matrix metalloproteinase-3 (MMP-3) in the plasma; however, plasma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α were increased. Our results showed that IL-6 and TNF-α may influence the deterioration effect of colitis in arthritic mice.

Ameliorative Effect of High-Dose Vitamin C Administration on Dextran Sulfate Sodium-Induced Colitis Mouse Model.

Vitamin C is a natural nutrient with antioxidant properties and is used as a health supplement. In this study, we examined the effects of intraperitoneal administration of high-dose vitamin C (4 g/kg) on dextran sodium sulfate (DSS)-induced ulcerative colitis. We prepared a mouse ulcerative colitis model by administering DSS for 7 d along with high-dose vitamin C each day during DSS treatment. Ulcerative colitis induced by DSS was ameliorated by high-dose vitamin C administration. Blood levels of interleukin-6, tumor necrosis factor-α, hydrogen peroxide (H2O2), and iron were elevated in DSS-treated mice but lowered by high-dose vitamin C administration. Contrarily, the levels of H2O2 and iron and the numbers of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells in the colon were further increased by high-dose vitamin C administration. The expression levels of fibroblasts, collagen type I, and collagen type III decreased in the DSS-treated mice but increased in mice administered high-dose vitamin C. These results suggest that high-dose vitamin C administration can improve ulcerative colitis.

Acute urinary retention in two adolescent girls with imperforate hymen.

Acute urinary retention is rare symptom in young adolescent girls. Imperforate hymen can be a cause of acute urinary retention possibly due to the pressure effect of the distended vagina (hematocolpos) on the lower urinary tract. However, the mechanism of progression to urinary retention is unknown. We report on two cases of adolescent girls with imperforate hymen who presented with acute urinary retention. A series of volume tolerance tests of the urinary bladder and urodynamic studies before operation revealed highly elevated urethral resistance, which was induced by interaction of large amount of urinary volume in the bladder and the large size of hematocolpos. After operation, urinary retention could not be observed and the urethral pressure returned to normal.

Anatomical-positional relationship between the bone structure of the distal radius and flexor pollicis longus tendon using ultrasonography.

PURPOSE: In this study, using an ultrasonography, we investigated the positional relationship between the volar bone cortex of distal radius and flexor pollicis longus (FPL) tendon in the distal radius of healthy subjects. METHODS: The subjects were 32 healthy volunteers (56 wrists) (Age 32.9 ± 8.5, 16 males and 16 females). Their wrists were imaged by an ultrasonography. The distances between the watershed line (WS) and FPL (A), between the distal margin of pronator quadratus (DMPQ) and FPL (B), between the FPL and volar radial bone cortex at the maximum muscle belly of the PQ muscle right below the sliding region of the FPL tendon (C), and between the WS and DMPQ (D) were measured. RESULTS: All these parameters showed a normal distribution. When the correlation among the parameters was investigated, a correlation with an index of the physique, BMI, was noted in A (P < 0.01), B (P < 0.01), and C (P < 0.01), but no correlation was noted only in D (P = 0.59). CONCLUSIONS: Our results were suggested that when distal radius fracture is treated with a distal plate placement, the appropriate placement can be achieved by applying about 3 mm additional dissection of soft tissue on the volar bone cortex distal to the DMPQ.

Administration of High-Dose Vitamin C and Irinotecan Ameliorates Colorectal Cancer Induced by Azoxymethane and Dextran Sodium Sulfate in Mice.

High-dose vitamin C administration has been reported to exhibit antitumor effect in various mouse models of cancer. However, the underlying mechanism of antitumor effect against colorectal cancer remains to be elucidated. In this study, we investigated the antitumor effect of high-dose vitamin C in a mouse model of chronic inflammation-associated colorectal cancer induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). After cancer induction, the mice were administered vitamin C and/or irinotecan. Because irinotecan is a key drug in colorectal cancer treatment, it was used for comparison in this study. We examined reactive oxygen species (ROS) and interleukin-6 (IL-6) levels in the plasma of mice, as well as collagen type I and caspase-1 expression and neutrophil and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cell counts in the colon tissue. Vitamin C and/or irinotecan administration decreased the plasma level of ROS and IL-6 and increased the expression of collagen type I and caspase-1. Furthermore, it increased neutrophil and TUNEL-positive cell counts. The most significant changes in the parameters analyzed were observed when both vitamin C and irinotecan were administered.

The Influence of Reactive Oxygen Species and Glucocorticoids on Dry Skin in a Mouse Model of Arthritis.

BACKGROUND: Dry skin induced by rheumatoid arthritis (RA) causes itching, which negatively influences a patient's quality of life. We previously reported that mast cells are related to dry skin in arthritic mice. However, the mechanism of mast cell activation is unclear. In this study, we examined the mechanism underlying the formation of dry skin induced by mast cells in arthritis that involves thymic stromal lymphopoietin (TSLP), neutrophils, reactive oxygen species (ROS), and glucocorticoids. METHODS: Mice with DBA/1JJmsSlc collagen-induced arthritis were treated with inhibitors or neutralizing antibodies. We measured transepidermal water loss (TEWL) to examine the modulating signal of mast cells. RESULTS: TEWL, the number of mast cells, and the plasma levels of TSLP, ROS, and corticosterone in the arthritic mice were increased when compared with the control mice. However, the mice treated with TSLP- and neutrophil-neutralizing antibodies and ROS and glucocorticoid receptor inhibitors (N-acetyl-L-cysteine [NAC] and RU-486, respectively) experienced an improvement. The ameliorating effect was most remarkable following treatment with NAC + RU-486. CONCLUSION: This study suggested that inhibiting ROS and glucocorticoids is important to ameliorate dry skin in arthritis, which may provide a novel treatment option for dry skin in RA patients.

Role of mast cells in the induction of dry skin in a mouse model of rheumatoid arthritis.

PURPOSE: Rheumatoid arthritis (RA) is known to induce dry skin as an extra-articular symptom. However, the mechanisms behind the induction are unclear. In this study, we utilized an arthritis mouse model to simulate RA to reveal the relationship between arthritis and dry skin. MATERIALS AND METHODS: DBA/1JJmsSlc control mice (n = 5) and DBA/1JJmsSlc collagen-induced arthritis mouse model (arthritis mice; n = 5) were used. We measured transepidermal water loss (TEWL) and capacitance to reveal the effect of arthritis on skin barrier function. In addition, we measured the expression of biomarkers of skin barrier function. RESULTS: We found that the hind limb volume of the arthritis mice was higher than that of the control mice. Our results showed that the arthritis mice had higher TEWL and lower capacitance when compared to the control mice. When compared to that of the control mice, the skin of the arthritis mice was thicker with more leukocyte infiltration. In the skin of arthritis mice, we observed lower expression of type I and IV collagens, but higher expression of matrix metalloproteinases (MMP)-1 and -9 when compared to that of the control mice. The levels of mast cells, histamine, substance P, and tryptase were higher in the arthritis mice than in the control mice. This study showed that the arthritis mice exhibited a disruption of skin barrier function (i.e. dry skin), which was improved following treatment with a mast cell inhibitor. CONCLUSIONS: Our results on mast cells suggested that an improvement of dry skin is important for RA management.

Characterization of dry skin associating with type 2 diabetes mellitus using a KK-Ay/TaJcl mouse model.

PURPOSE: Type 2 diabetes mellitus (DM) induces various dermatological conditions that can affect patient quality of life, including increased susceptibility to skin infections and dry skin. While the mechanisms that underlie the causes of dry skin in type 1 DM have been widely studied, how type 2 DM elicits similar effects is unclear. The purpose of this study was therefore to evaluate skin barrier and hydration function using a KK-Ay/TaJcl mouse model of type 2 DM. MATERIALS AND METHODS: KK-Ay/TaJcl and control mice were housed separately for 4 weeks and then body weight, water intake, urine production, and blood glucose levels were measured. Skin barrier function was estimated by assessing transepidermal water loss (TEWL) and hydration levels of the stratum corneum. The expression levels of various skin biochemical factors were also examined by western blot, including type 1 collagen, mast cell tryptase, hyaluronic acid binding protein (HABP), and fibroblast protein S100A4. RESULTS: Compared to control mice, there was a marked increase in body weight, water intake, urine production, and blood glucose levels in the KK-Ay/TaJcl mice over the length of the experiment. Hydration levels in the stratum corneum were lower in KK-Ay/TaJcl mice compared to control mice, although TEWL was not significantly different between groups. We also found that hyaluronic acid binding protein expression was higher in KK-Ay/TaJcl mice, although other biochemical factors were the same. CONCLUSIONS: These findings suggest that hyaluronic acid associates with the dry skin caused by type 2 DM. This contributes to understanding this phenomenon and may lead to better treatment options for patients in the future.

Evaluation of the pulley function of the hamulus of the hamate for the flexor tendons.

PURPOSE: The aim of this study was to measure the curvature radii of the finger flexor tendons on CT acquired using tendon conditions to examine whether the hamulus of the hamate functions as a pulley of the flexor tendon. METHODS: The subjects were 20 healthy volunteers (40 hands) (14 males and 6 females, mean age: 27.5 years old). Their hands were imaged in extension and flexion of the fingers on CT. The curvature radii of the little and middle finger flexor tendons at the hamulus of the hamate were calculated. RESULTS: The curvature radii of the little and middle finger flexor tendons were 24.8 ± 7.3 and 327.1 ± 343.9 mm in finger extension, respectively, and 21.3 ± 5.3 and 265.1 ± 202.9 mm in finger flexion, respectively. The curvature radius of the little finger flexor tendon was significantly smaller than that of the middle finger flexor tendon in both finger extension and flexion (P < 0.01). CONCLUSIONS: Our study suggested that the hamulus of the hamate functions as a pulley for the little finger flexor tendon.

[Acute Aortic Insufficiency due to the Avulsion of Aortic Valve Commissure;Report of a Case].

A 61-year-old man with a history of hypertension and cerebral infarction, presented to a clinic with sudden dyspnea at rest. He was diagnosed with heart failure and referred to our hospital. Echocardiography and three-dimensional computed tomography showed acute heart failure and aortic insufficiency due to avulsion of the aortic valve commissure between the right coronary cusp and the non-coronary cusp. He had no symptoms such as fever or infection and no history of rheumatic disease. He underwent intima fixation of the avulsed commissure and aortic valve replacement using a tissue valve because acute left heart failure was refractory to medical treatment. Postoperative echocardiography demonstrated good left ventricular contraction without any aortic regurgitation. He was discharged on the 35th postoperative day.