Erucin inhibits osteoclast formation via suppressing cell-cell fusion molecule DC-STAMP without influencing mineralization by osteoblasts.

OBJECTIVE: Erucin (ERN), an isothiocyanate, is derived from the vegetable arugula. Although ERN has antitumor and antioxidant activity, the effect of ERN on osteoclast and osteoblast differentiation is not well documented. In this study, we evaluated the effects of ERN on osteoclast and osteoblast differentiation in vitro. RESULTS: ERN significantly reduced the formation of 1α,25(OH)2D3-induced tartrate-resistant acid phosphatase (TRAP)-positive cells at non-cytotoxic concentrations. Furthermore, ERN downregulated the mRNA expression of osteoclast-associated genes, such as nuclear factor of activated T cells cytoplasmic-1, TRAP, and cathepsin K. In addition, ERN suppressed mRNA expression of dendritic cell specific transmembrane protein (DC-STAMP), which encodes cell-cell fusion. However, ERN did not affect mineralization by osteoblasts. Thus, our data suggest that ERN may attenuate osteoclastic bone resorption by inhibiting multinucleation of mononuclear pre-osteoclasts and by suppressing mRNA expression of DC-STAMP in bone marrow cells without influencing mineralization by osteoblasts.

The first case of SMARCA4-deficient sarcoma of stomach.

SMARCA4-deficient sarcoma was first reported in the chest and recently in the uterus, but not in the stomach. Here, we present a patient diagnosed with SMARCA4-deficient sarcoma of the stomach, using histochemistry. An emergency operation was performed due to perforation of the tumor. However, one month after the operation, two nodes recurred, and six cycles of combination chemotherapy consisting of adriamycin and ifosfamide were administered. The combination chemotherapy showed a remarkable effect, and complete remission was achieved. The patient was alive without recurrence after 48-month follow-up. SMARCA4-deficient sarcoma is an exceedingly rare tumor with an extremely poor therapeutic response to anticancer drugs. Herein, we present the first case of SMARCA4-deficient sarcoma of the stomach, where a complete response to chemotherapy was achieved.

Radiofrequency Ventro-oral Thalamotomy for Post-stroke Focal Dystonia in a Pediatric Patient.

Dystonia is a movement disorder that has various treatment options. For primary dystonia, stereotactic procedures such as deep brain stimulation (DBS) have demonstrated favorable outcomes. For secondary dystonia, however, the treatment outcomes remain inconclusive, and the heterogeneous etiological background is considered to contribute to the poor outcomes of the disease. Here, we report a rare pediatric case of post-stroke focal dystonia treated with conventional radiofrequency ventro-oral (Vo) thalamotomy. The patient was an 11-year-old girl with secondary focal dystonia in her right hand. The dystonia was considered to result from a stroke lesion in the putamen due to vasculitis following varicella-zoster virus infection. We hypothesized that the infarction of the putamen resulted in hyperactivity in the thalamus, and, thus, performed a radiofrequency Vo thalamotomy. Markedly decreased muscle tone in her right hand was noted immediately after surgery. However, the improvement was temporary, as her symptoms returned to baseline level by the 6-month follow-up. Although the observed improvement was temporary in this case, our findings may elucidate the possible mechanisms of secondary focal dystonia. Further studies are needed to establish an effective surgical treatment for secondary focal dystonia.

Insulin resistance: Relationship between indices during late gestation in dairy cows and effects on newborn metabolism.

To investigate the relationship between insulin resistance indices ["Revised quantitative insulin sensitivity check index" (RQUICKI; RQ), "Revised quantitative insulin sensitivity check index - ß-hydroxybutyrate" (RQUICKIBHB ; RQBHB ), and "Homeostasis model assessment-insulin resistance" (HOMA-IR; HR)], and metabolic parameters in dams during late gestation, and their newborn calves. Blood was sampled twice weekly during the experimental period in 30 dry Holstein cows. In calves, blood sampling and body weight measurements were performed immediately after birth, and in 1-week-old male calves, liver and muscle biopsy samples were obtained for determining metabolic factor mRNA levels. RQ and RQBHB were negatively correlated with insulin, nonesterified fatty acid, BHB, and albumin and were positively correlated with leptin levels in blood during late gestation (p < .05). RQ, rather than RQBHB , reflected metabolism of dams, while stronger positive correlations were present between HR and blood insulin concentrations than other parameters, and calves of dams with high HR had low body weight, and high liver and muscle expression of growth hormone and insulin receptor mRNA (p < .05). RQ and HR of dams during late gestation could serve as indicators of dam metabolism and predictors of metabolism in newborn calves respectively.

Sulforaphene attenuates multinucleation of pre-osteoclasts by suppressing expression of cell-cell fusion-associated genes DC-STAMP, OC-STAMP, and Atp6v0d2.

We assessed the effect of sulforaphene (SFE) on osteoclast differentiation. SFE significantly decreased the number of RANKL-induced tartrate-resistant acid phosphatase-positive cells and suppressed pre-osteoclast multinucleation. Furthermore, SFE downregulated mRNA expression of DC-STAMP, OC-STAMP, and Atp6v0d2, which encode cell-cell fusion molecules. Our data suggest that SFE attenuates pre-osteoclast multinucleation via suppression of cell-cell fusion.

Sulforaphane inhibits osteoclast differentiation by suppressing the cell-cell fusion molecules DC-STAMP and OC-STAMP.

Sulforaphane (SFN), a kind of isothiocyanate, is derived from broccoli sprouts. It has anti-tumor, anti-inflammatory, and anti-oxidation activity. The molecular function of SFN in the inhibition of osteoclast differentiation is not well-documented. In this study, we assessed the effect of SFN on osteoclast differentiation in vitro. SFN inhibited osteoclast differentiation in both bone marrow cells and RAW264.7 cells. Key molecules involved in the inhibitory effects of SFN on osteoclast differentiation were determined using a microarray analysis, which showed that SFN inhibits osteoclast-associated genes, such as osteoclast-associated receptor (OSCAR), nuclear factor of activated T cells cytoplasmic-1, tartrate-resistant acid phosphatase, and cathepsin K. Moreover, the mRNA expression levels of the cell-cell fusion molecules dendritic cell specific transmembrane protein (DC-STAMP) and osteoclast stimulatory transmembrane protein (OC-STAMP) were strongly suppressed in cells treated with SFN. Furthermore, SFN increased the phosphorylation of signal transducer and activator of transcription 1 (STAT1), a regulator of macrophage and osteoclast cell fusion. Thus, our data suggested that SFN significantly inhibits the cell-cell fusion molecules DC-STAMP and OC-STAMP by inducing the phosphorylation of STAT1 (Tyr701), which might be regulated by interactions with OSCAR.

[Surgical Outcome of Acute and Subacute Subdural Hematoma with Endoscopic Surgery].

Acute subdural hematoma (ASDH) and subacute subdural hematoma(SASDH)evacuations are commonly performed through a large craniotomy or with external decompression surgery to avoid secondary brain injury. In the field of head trauma, minimally invasive surgeries performed with neuroendoscopy were recently reported. We report 12 patients with ASDH( n=9) and SASDH (n=3)w ho underwent endoscopic hematoma evacuation via a small craniotomy between November 2013 and May 2015. All patients were over 65 years of age(mean age, 78.8 years[range, 65-91 years]) and had subdural hematomas without extensive contusion. The mean preoperative Glasgow Coma Scale(GCS)score was 8.75 (range, 4-13). In three patients, we observed the bleeding point and substantially coagulated it. Decompression in all patients was adequate after surgery. Patients with a preoperative GCS score of 4-6 showed poor outcomes, whereas those with a score >9 showed relatively good outcomes. We performed the operations safely in patients who were on antithrombotic therapy or had a systemic bleeding tendency pre-injury. Endoscopic hematoma evacuation via a small craniotomy is a safe and minimally invasive procedure in patients older than 65 years with comorbidities.