Cucurbitacin B induces neurogenesis in PC12 cells and protects memory in APP/PS1 mice

Cucurbitacin B (CuB) isolated from Cucumis melo by using a PC12 cell bioassay system exhibited significant nerve growth factor (NGF)-mimic or NGF-enhancing activity in PC12 arid primary neuron cells. It was also demonstrated pro-neurogenesis effects in ICR and APP/PSI mice and improved memory deficit of APP/PSI mice. Its possible mechanism includes significant induction of the phosphorylation of glucocorticoid receptor (GR), protein kinase C (PKC), phospholipase C (PLC) and inhibition of cofilin. ChemProteoBase profiling, binding assay and cellular thermal shift assay (CETSA) were used to determine the target protein. Results revealed that CuB could affect actin dynamics as an actin inhibitor but did not bind with GR. The protein level of cofilin in PC12 cells after treating 0.3 mu M and different temperatures was significantly higher than that of control group. Other neurotrophic signalling pathways, such as TrkA/TrkB, were analysed with specific inhibitors and Western blot. The inhibitors of TrkA, PLC, PKC, Ras, Raf and ERK1/2 significantly decreased the percentage of PC12 cells with neurite outgrowth and shortened the length of neurite outgrowth induced by CuB. CuB significantly induced the phosphorylation of TrkA, ERK and CREB. The phosphorylation of these proteins was obviously decreased by their specific inhibitors. These results suggest that cofilin is a candidate target protein of CuB in PC12 cells and that the GR/PLC/PKC and TrkA/Ras/Raf/ERK signalling pathways play important roles in the neuroprotective effect of CuB.11Ysciescopu

Esophageal granular cell tumor successfully resected by endoscopic submucosal dissection

Granular cell tumors of the esophagus are rare neoplasms and their diagnosis is mainly based on histopathologic examination of endoscopic biopsies. With the development of endoscopic techniques, there has been a marked increase in local treatment modalities for early esophageal neoplasms. In this case report, we describe the removal of a granular cell tumor by the endoscopic submucosal dissection technique, and briefly discuss the literature on clinicopathologic aspects and management of granular cell tumors

Inhibition of mitochondrial complex I by the novel compound FSL0260 enhances high salinity-stress tolerance in Arabidopsis thaliana

Chemical priming is an attractive and promising approach to improve abiotic stress tolerance in a broad variety of plant species. We screened the RIKEN Natural Products Depository (NPDepo) chemical library and identified a novel compound, FSL0260, enhancing salinity-stress tolerance in Arabidopsis thaliana and rice. Through transcriptome analysis using A. thaliana seedlings, treatment of FSL0260 elevated an alternative respiration pathway in mitochondria that modulates accumulation of reactive oxygen species (ROS). From comparison analysis, we realized that the alternative respiration pathway was induced by treatment of known mitochondrial inhibitors. We confirmed that known inhibitors of mitochondrial complex I, such as rotenone and piericidin A, also enhanced salt-stress tolerance in Arabidopsis. We demonstrated that FSL0260 binds to complex I of the mitochondrial electron transport chain and inhibits its activity, suggesting that inhibition of mitochondrial complex I activates an alternative respiration pathway resulting in reduction of ROS accumulation and enhancement of tolerance to salinity in plants. Furthermore, FSL0260 preferentially inhibited plant mitochondrial complex I rather than a mammalian complex, implying that FSL0260 has a potential to be an agent for improving salt-stress tolerance in agriculture that is low toxicity to humans

Osteochondritis Dissecans of the Humeral Capitellum in Young Athletes Comparison Between Baseball Players and Gymnasts

Background: Osteochondritis dissecans (OCD) lesions are often observed in the humeral capitellum both in young baseball players and gymnasts. It is generally believed that capitellar OCD in baseball players can be seen on an anteroposterior (AP) radiograph with the elbow in 45° of flexion. However, the mechanism of injury seems to be different in baseball players and gymnasts. Repetitive valgus overload with the elbow in flexion is believed to be the cause of capitellar OCD lesions in baseball players, whereas weightbearing with the elbow in extension may be the cause of OCD in gymnasts. Purpose: To determine the difference in capitellar OCD location between baseball players and gymnasts and to propose the optimal AP radiographic angle of the elbow for visualization of early-stage OCD lesions in adolescent gymnasts. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Subjects consisted of 95 baseball players (95 elbows) and 21 gymnasts (24 elbows) with a mean age of 13.7 years (range, 11-18 years). To localize the lesion, inclination of the affected area in the humeral capitellum against the humeral axis was investigated using sagittal computed tomography images of the elbow. The inclination angle was defined as the angle between the long axis of the humerus and the line perpendicular to a line that connected the anterior and posterior margin of the lesion. The inclination angle in each group was compared and statistically analyzed. Results: The mean inclination angle was 57.6° ± 10.7° in baseball players and 28.0° ± 10.7° in gymnasts. Capitellar OCD lesions were located more anterior in baseball players when compared with gymnasts (P < .01). Conclusion: Due to differences in applied stress, capitellar OCD lesions in baseball players were located more anteriorly compared with those seen in gymnasts. Therefore, although AP radiographs with the elbow in 45° of flexion are optimal for detecting OCD lesions in baseball players, radiographs with less elbow flexion or full extension are more useful in gymnasts, especially in early-stage OCD

Methyl 3‑((6-Methoxy-1,4-dihydroindeno[1,2‑<i>c</i>]pyrazol-3-yl)­amino)­benzoate (GN39482) as a Tubulin Polymerization Inhibitor Identified by MorphoBase and ChemProteoBase Profiling Methods

A series of indenopyrazoles was synthesized from the corresponding indanones and phenyl isothiocyanates in two steps. Among the compounds synthesized, methyl 3-((6-methoxy-1,4-dihydroindeno­[1,2-<i>c</i>]­pyrazol-3-yl)­amino)­benzoate <b>6m</b> (GN39482) was found to possess a promising antiproliferative activity toward human cancer cells without affecting any antimicrobial and antimalarial activities at 100 nM. Both a methoxy group at R¹ position and a methoxycarbonyl group at R² position of the anilinoquinazoline framework are essential for the high cell growth inhibition. Both MorphoBase and ChemProteoBase profiling analyses suggested that compound <b>6m</b> was classified as a tubulin inhibitor. Indeed, compound <b>6m</b> inhibited the acetylated tubulin accumulation and the microtubule formation and induced G2/M cell cycle arrest in HeLa cells, revealing that a promising antiproliferative activity of compound <b>6m</b> toward human cancer cells is probably caused by the tubulin polymerization inhibition