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1,6- O, O-Diacetylbritannilactone (OODBL), a plant sesquiterpene lactone, was previously reported to show multiple pharmacological effects such as anti-cancer and anti-inflammatory activities. In this study, we investigated the anti-inflammatory effect of OODBL on interleukin (IL)-4-induced signal transducer and activator of transcription 6 (STAT6) signaling pathway in human lung A549 cells. We found that OODBL dramatically inhibited IL-4-induced messenger RNA (mRNA) expression of eotaxin-1 and arachidonate 15-lipoxygenase-1 (ALOX15) in a dose-dependent manner. To clarify the action mechanism of OODBL, we examined the effect of OODBL on activation of STAT6. OODBL decreased both STAT6 phosphorylation and reporter gene activity. Furthermore, OODBL suppressed phosphorylation of Janus Kinase 3 (JAK3) without affecting JAK1. Taken together, OODBL abolished IL-4-induced eotaxin-1 and ALOX15 mRNA expressions by repressing the activation of STAT6 and JAK3. These results suggest that OODBL has a potential therapeutic efficacy on inflammatory diseases especially allergic airway disease as a lead compound. [ABSTRACT FROM AUTHOR]

Bee venom has been used for treating various diseases for a long time. However, the bioactive constituents of bee venom and its mechanisms remain poorly understood. In the present study, phospholipase A 2 ( Bt-PLA 2 ) cDNA was cloned, and a mature form of Bt-PLA 2 was purified from bumblebee venom ( Bombus terrestris ). The differentiation induction and apoptosis induction activities of Bt-PLA 2 on chronic myelogenous leukemia (CML) K562 cells were also evaluated. Bt-PLA 2 cDNA has 540 nucleotides that encode a 180-amino-acid protein. The purified, mature form of Bt-PLA 2 was an 18-kDa protein, and it inhibited K562 cell growth, determined by an IC 50 value of 29.5 ng/μl. Moreover, Bt-PLA 2 induced erythroid differentiation of K562 cells in a dose-dependent manner, and this was supplemented with the upregulation of glycophorin A (GPA) mRNA expression. Bt-PLA 2 -induced apoptosis, analyzed by DAPI staining, was correlated with the result analyzed by AnnexinV-FITC/PI binding. Furthermore, activation of caspase 3 and poly ADP-ribose polymerase (PARP) and inhibition of p-Akt, determined by western blot, further demonstrated that Bt-PLA 2 induced apoptosis mainly through the Akt pathway. The parallel induction of erythroblasts differentiation of K562 cells and apoptosis due to Bt-PLA 2 treatment demonstrated the potential use of Bt-PLA 2 as an anti-leukemia drug lead. [ABSTRACT FROM AUTHOR]

Mulberry (Morus spp.) is a multipurpose tree that is worldwide planted because of its economic importance. This study was to investigate the likely consequences of anticipated future elevated CO2 (eCO2) on growth, physiology and nutrient uptake of nitrogen (N), phosphorus (P) and potassium (K) in two most widely cultivated mulberry (Morus multicaulis Perr.) varieties, QiangSang-1 and NongSang-14, in southwest China. A pot experiment was conducted in environmentally auto-controlled growth chambers under ambient CO2 (ACO2, 410/460 ppm, daytime/nighttime) and eCO2 (710/760 ppm). eCO2 significantly increased plant height, stem diameter, leaf numbers and biomass production, and decreased chlorophyll concentrations, net photosynthetic rate, stomatal conductance and transpiration rate of these two mulberry varieties. Under eCO2 leaf N and P, and root N, P and K concentrations in both mulberry varieties decreased, while plant total P and K uptake in both varieties were enhanced, and an increased total N uptake in NongSang-4, but not in QiangSang-1. Nutrient dilution and transpiration rate were the main factors driving the reduction of leaf N and P, whereas changes in plant N and P demand had substantial impacts on photosynthetic inhibition. Our results can provide effective nutrient management strategies for a sustainable mulberry production under global atmosphere CO2 rising scenarios. [ABSTRACT FROM AUTHOR]

Background: Mild to moderate thalassemia trait (TT) and iron deficiency anemia (IDA) are the most common conditions of microcytic hypochromic anemia (MHA) and they exhibit highly similar clinical and laboratory features. It is sometimes difficult to make a differential diagnosis between TT and IDA in clinical practice. Therefore, a simple, effective, and reliable index is needed to discriminate between TT and IDA., Methods: Data of 598 patients (320 for TT and 278 for IDA) were enrolled and randomly assigned to training set (278 of 598, 70%) and validation set (320 of 598, 30%). Stepwise discriminant analysis was used to define the best diagnostic formula for the discrimination between TT and IDA in training set. The accuracy and diagnostic performance of formula was tested and verified by receiver operating characteristic (ROC) analysis in validation set and its diagnostic performance was compared with other published indices., Results: A novel formula, Thalassemia and IDA Discrimination Index (TIDI) = -13.932 + 0.434 × RBC + 0.033 × Hb + 0.025 ×MCHC + 53.593 × RET%, was developed to discriminate TT from IDA. TIDI showed a high discrimination performance in ROC analysis, with the Area Under the Curve (AUC) = 0.936, Youden' s index = 78.7%, sensitivity = 89.5%, specificity = 89.2%, respectively. Furthermore, the formula index also obtained a good classification performance in distinguishing 5 common genotypes of TT from IDA (AUC from 0.854-0.987)., Conclusion: The new, simple algorithm can be used as an effective and robust tool for the differential diagnosis of mild to moderate TT and IDA in Guangxi region, China., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Metastasis is the main cause of the lethality of prostate cancer. Class I phosphatidylinositol 3-kinases (PI3Ks), which contain 4 isoforms, α, β, δ, and γ, are known to play important roles in cell growth, migration, invasion, and so on. However, the respective role of each PI3K isoform in cancer cell migration and invasion remains unknown. In a study that aimed to elucidate the respective role of the 4 PI3K isoforms, we investigated the change in migratory and invasive ability of DU145 cells after treatment with each PI3K isoform-specific inhibitor. Both migration and invasion of DU145 cells were potently blocked by each of the PI3Kβ inhibitors (GSK2636771 and TGX221) and PI3Kδ inhibitors (CAL101 and IC87114) while not obviously affected by PI3Kα inhibitor BYL719 or PI3Kγ inhibitor AS252424. Furthermore, knocking down PI3Kβ or PI3Kδ isoform led to a significant decrease in migration of DU145. The results suggest that PI3Kβ and PI3Kδ play key roles in prostate cancer cell migration, while PI3Kα and PI3Kγ might be redundant. Oral administration of GSK2636771 (100 mg/kg) and CAL101 (30 mg/kg) inhibited tumor growth in bone, an experimental model by intratibia injection of DU145 cells, with improved bone structure and bone mineral density analyzed by micro-computed tomography. Tissue staining indicated reduction of metastatic DU145 cells and osteoclasts in the bones of GSK2636771- and CAL101-treated mice compared to the untreated group. In summary, our results indicated the distinct roles of 4 PI3K isoforms in the migration of prostate cancer DU145 cells, and they demonstrated the in vitro and in vivo antimetastatic effect of PI3K-isoform specific inhibitors, most of which are in clinical trials.-Zhang, Z., Liu, J., Wang, Y., Tan, X., Zhao, W., Xing, X., Qiu, Y., Wang, R., Jin, M., Fan, G., Zhang, P., Zhong, Y., Kong, D. Phosphatidylinositol 3-kinase β and δ isoforms play key roles in metastasis of prostate cancer DU145 cells.

Olfactory neuroblastoma (ONB) is a kind of rare and complex head and neck tumor. The reports on this field are very scarce due to the low morbidity. Here, we summarized the clinical features and prognosis of ONB through analysis of 10 cases, and determined the phosphorylation status of some molecules known to be involved in carcinogesis such as Akt, Erk, Stat3 and Stat5 in ONB tissue. Ten ONB patients were recruited in this study, 6 male and 4 female, ranging from 26 to 66 years old. In the 10 cases, 6 were diagnosed as late T stage (T 3 /T 4 ), 6 were at late Kadish stage (C/D) and 3 were at high Hyams grade (Ⅲ), which indicated a poorer prognosis. Patient characteristics-gender and tumor features were evaluated with respect to the overall survival (OS) through univariate analysis. The result indicated that the OS of male is obviously higher than that of female after a series of combined treatment. The OS of ONB patients in the late stage or high grade is lower than those in early stages or low grade. Moreover, p-Akt, p-Erk, p-Stat3 and p-Stat5 was detected in 5 (50%), 9 (90%), 7 (70%) and 0 patients (0%), respectively, suggesting the former 3 molecules might be potential biomarkers for diagnosis of ONB., (Copyright © 2018. Published by Elsevier GmbH.)