Interference with PLA2G16 promotes cell cycle arrest and apoptosis and inhibits the reprogramming of glucose metabolism in multiple myeloma cells by modulating the Hippo/YAP signaling pathway.

Multiple myeloma, which is a clonal plasma cell tumor, derives from a postmitotic lymphoid B-cell lineage and remains untreatable. Group XVI phospholipase A2 (PLA2G16) can either be a tumor suppressor or an oncogene in different types of cancer. This study was intended to explore the role of PLA2G16 in multiple myeloma and to reveal the reaction mechanism. The mRNA and protein expressions of PLA2G16 in human bone marrow stromal cell line HS-5 and multiple myeloma cells were assessed using reverse transcription-quantitative PCR and western blot. The transfection efficacy of sh-PLA2G16 and oe-YAP was examined using reverse transcription-quantitative PCR and western blot. Through cell counting kit-8 assay and 5-ethynyl-2'- deoxyuridine staining, multiple myeloma cell viability and proliferation were detected. Flow cytometry was used to measure cell apoptosis and cell cycle distribution. Oxygen consumption rate, the activities of mitochondrial respiratory chain complexes I-V, and the activity of caspase-3 were estimated with Seahorse XF24 analyzer, oxidative phosphorylation activity assay kit, and caspase-3 assay kit, respectively. Lactate production and glucose consumption were evaluated usingcorresponding assay kits. Western blot was employed to meaure proteins associated with cell cycle, glycolysis, pentose phosphate pathway as well as Hippo/YAP signaling pathway. In this study, PLA2G16 expression was greatly increased in multiple myeloma cells and PLA2G16 silence inhibited cell proliferation, promoted cell apoptosis, facilitated cell cycle arrest, and suppressed the reprogramming of glucose metabolism in multiple myeloma. It was also identified that PLA2G16 depletion inhibited the Hippo/YAP signaling pathway. Further experiments revealed that the overexpression of YAP partially reversed the inhibitory effects of PLA2G16 silence on multiple myeloma cell malignant development and the reprogramming of glucose metabolism. Collectively, PLA2G16 silence impeded multiple myeloma progression and inhibited glucose metabolism reprogramming by blocking the Hippo/YAP signaling pathway.

Bortezomib, epirubicin, and dexamethasone (PAD) results in superior free-progression survival compared to bortezomib, cyclophosphamide, and dexamethasone (VCD) treatment in non-transplantation newly diagnosed multiple myeloma patients aged between 50 to 65: a retrospective single-center analysis in non-transplant patients.

Background: To explore the optimum induction therapy for patients with newly diagnosed multiple myeloma (NDMM) who are eligible but have not yet received autologous stem cell transplantation (ASCT) in China. Methods: A total of 140 NDMM patients with cytogenetic background were selected from the Chang Zheng Hospital for this study. The induction therapy consisted of combined bortezomib (1.3 mg/m2, i.v.), cyclophosphamide (200 mg, i.v.), and dexamethasone (20 mg, i.v.) (VCD); or combined bortezomib (1.3 mg/m2, i.v.), epirubicin (50 mg/m2, i.v.), and dexamethasone (20 mg, i.v.) (PAD). All patients received 4-6 cycles of induction therapy until the first remission (defined as reaching at least partial remission), followed by thalidomide (100 mg/every night, p.o.) as the maintenance therapy. Data was analyzed using SPSS18.0 software and Kaplan-Meier and Cox regression analyses. Results: Of the 140 patients enrolled, 56 were treated with VCD and 84 received the PAD regimen. Compared to patients treated with VCD, patients receiving PAD treatment showed better free-progression survival (PFS) (hazard ratio: 0.355; 95% confidence interval: 0.214 to 0.591; P<0.001) and response rates, defined as achieving very good partial response (VGPR) or better (VCD vs. PAD: 47/56 or 83.9% vs. 77/84 or 92.8%; P=0.087). Similarly, the superior efficiency of PAD treatment was observed in different cytogenetic abnormality subgroups, even in patients with 1q21 amplification. Conclusions: This analysis demonstrated that PAD treatment resulted in better PFS compared to VCD in NDMM patients (aged 50-55 years old) who are eligible for but refuse ASCT therapy.

Water management of alternate wetting and drying combined with phosphate application reduced lead and arsenic accumulation in rice.

Lead (Pb) and arsenic (As) exist in soil with different ionic forms, and it is difficult to immobilize simultaneously Pb and As in soil. The objective of this study is to determine the effects of water management including flooding (FL), alternate wetting and drying (AWD) and dry farming (DF) combined with addition of phosphate (P) on the accumulation of Pb and As in rice. Our results showed that Pb accumulated in root during vegetative stage, and most of As in root was transported to the above ground parts during the reproductive stage. Pb was evenly distributed in grains, and As was mostly accumulated in bran and aleurone layer. Water management had a reverse effect on the accumulation of Pb and As in rice. However, the effects of P on arid soil environment and Pb, As accumulation in rice were stronger than that in flooded soil. Application of P under AWD treatment could maintain a similar quantity of Fe plaque with flooding, decrease the availability of Pb in rhizosphere soil, reduce Pb and As accumulation in root, and result in the reduction of Pb and As accumulation in grains by 86% and 66% respectively. Besides, our study also found that flooding or AWD during vegetative stage facilitated the formation of iron plaque. In conclusion, AWD combined with P application could maintain a relatively lower concentrations of Pb and As in grains.

The neutrophil-lymphocyte ratio and immunosuppressive acidic protein may be useful parameters for predicting depression among middle-aged patients with diffuse large B cell lymphoma.

BACKGROUND: Patients with diffuse large B cell lymphoma (DLBCL) may experience depression. Growing evidence shows that depression interacts with immunity. However, the relationship between depression and immunity among DLBCL patients has not been investigated, despite reports indicating that patients with DLBCL often suffer from depression. METHODS: To accurately investigate the relationship between depression and immunity, 82 primarily diagnosed middle-aged patients with DLBCL who received standard chemotherapy were enrolled. The patients were divided into depressed and nondepressed groups according to Zung Self-rating Depression Scale (SDS) scores. Prozac was used to treat patients with depression until their symptoms were alleviated. The concentration of immunosuppressive acidic protein (IAP); percentages of cluster of differentiation (CD)3+, CD4+, and CD8+ T lymphocytes and CD56+ natural killer (NK) cells; absolute lymphocyte count (ALC); and neutrophil--lymphocyte ratio (NLR) were calculated at enrollment and after treatment. RESULTS: A higher score on the depression test was positively associated with serum IAP levels and NLR, and negatively associated with ALC. The levels of NLR and serum IAP in the depressed patients were significantly higher compared to those in the nondepressed patients. CONCLUSIONS: Our results suggest for the first time that IAP and the NLR are closely correlated with depression and may be parameters for predicting depression.

Lead was mobilized in acid silty clay loam paddy soil with potassium dihydrogen phosphate (KDP) amendment.

The immobilization effectiveness between Pb and phosphorus in soil varies with soil types. To clarify the effect of phosphate on the availability of Pb in agricultural soil, a culture experiment with three types of paddy soil was performed with potassium dihydrogen phosphate (KDP) added. EDTA, DGT and in-situ solution extraction methods were used to represent different available Pb content. Results showed that the concentration of EDTA-Pb in HN soil was slightly elevated after exogenous KDP added. The supplement of 300 mg/kg KDP significantly increased the content of soluble Pb in both acid silty clay loam soil and neutral silty loam soil (increased by 104.65% and 65.12%, respectively). However, there was no significant influence of KDP on the concentration of DGT extracted Pb. XANES results showed that Pb(OH)2, PbHPO4, humic acid-Pb and GSH-Pb were the major speciation of Pb in soil colloids. The proportion of Pb(OH)2 and humic acid-bounded Pb in soil colloids were elevated after exogenous KDP added. Our results indicated that there was a mobilization effect of KDP on Pb by increasing the amount of colloidal Pb in soil solution, especially in acid silty clay loam paddy soil. Such colloid-facilitated transport might promote the uptake of Pb in rice and pose a potential threat to human health.