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The metabolic reprogramming is an important basis for the development of many tumors, including prostate cancer (PCa). Metabolic changes in many amino acids consist of serine and glycine affect the biological behavior of them. Phospholipase C epsilon (PLCε) plays an important role as an oncogene. However, its role in regulating amino acid metabolism remains unclear. In this study, results found significantly positive correlation between PLCε and Yes-associated protein (YAP) in PCa tissues. LC-MS/MS and GC-MS results further displayed abnormally elevated levels of serine, glycine and its some downstream metabolites in the blood of PCa patients. Secondly, PLCε knockdown can inhibit serine/glycine producing and proliferation of PCa both in vivo and in vitro. Mechanistically, PLCε may affect the serine/glycine metabolism by regulating dephosphorylation and nuclear translocation of YAP. More interestingly, verteporfin (VP, a specific inhibitor of YAP) could effectively enhance the PLCε-depletion induced inhibition of serine/glycine secretion and growth. Overall, this research revealed the possibility of anomalous serine/glycine levels in the blood for the diagnosis of PCa, identified the important role of the PLCε/YAP axis in regulating serine/glycine metabolism, cell proliferation and tumor growth, and suggested the combination of VP with PLCε-depletion may provide a new idea for the treatment of PCa.

Dissolved organic matter (DOM) in karst water is one of the most important carbon sink components, whose origins, distributions, and transport processes are of significance to carbon sink studies. Chromophoric dissolved organic matter (CDOM) can be utilized to express the composition and structural properties of DOM. In this paper, water samples were collected monthly from Xueyu Cave in a karst underground river from both inside and outside the cave. The changes in hydrochemistry and CDOM spectral characteristics as well as the influencing factors for CDOM changes were studied, with the aim of providing experimental support for carbon sink fluxes in karst processes. The main results were as follows. ① The dominant type of CDOM in Xueyu Cave karst water consisted of small molecular weight organic matter that was autochthonously derived and easily bio-degraded, and the tryptophan-like and tyrosine-like components accounted for more than 60% of the total CDOM. ② The most effective influencing factor inside the cave was microbes, which degraded the small molecular DOM in groundwater and induced slight decreases in the TOC and DOC concentrations; they also increased the humic index (HIX). ③ However, the dominant factor outside the cave was submerged aquatic plant photosynthesis, which induced significant increases in the TOC and DOC concentrations and autochthonous small molecular weight DOM contents.

This study was designed to elucidate the chemical composition and anti-cancer effects of Schizonepeta tenuifolia’s ethanol extracts. Microfluidic technology was used in the study of Schizonepeta tenuifolia from 9 different geographic regions. The ethanol extracts were examined with HPLC to establish their Fingerprints in order to analyze the relationship between the spectrum and efficacy index through Grey Correlation software, and a rapid HPLC-Q-TOF/MS method was established. The result shows that chromatographic peaks of the 19, 6, 11, 16, 18th are the representative diosmetin, luteoloside, hesperidin, luteolin, and apigenin. The 10, 12, 20th peaks may be naringenin-7-O-glucuronide or quercitrin, rosmarinate or acetylcorynoline, and 5,7-dihydroxy-6,4-dimethoxy flavone. The major chemical composition of Schizonepeta tenuifolia was found to have the anti-lung-tumor effects. A new method was established for the quality control of traditional Chinese medicine.

To explore the effect of arsenic trioxide combined with itraconazole on proliferation and apoptosis of KG1a cells and its potential mechanism.The cell morphology was observed with Wrighe-Giemsa staining; cell survival rate was examined by CCK-8; and colony formation capacity was measured by methylcellulose colony formation test; the flow cytometry was used to analyse the cell apoptosis rate and cell cycle; the protein expressions of BCL-2,caspase-3,BAX,SMO,Gli1 and Gli2 were detected by Western-blot.The arsenic trioxide and itraconazole alone both could inhibit the KG1a cell proliferation in dose-and time-dependent manner. In comparison between single and combined drug-treatment group, both the cell survival rate and the colony number of the single drug-treatment group were significantly lower(P0.05), and the apoptosis rate was higher in the combined drug-treatment group. In the combined-treatment group, the protein expression of Caspase-3 and BAX was upregulated, while the protein expression of BCL-2,SMO,Gli1 and Gli2 was downregulated.Arsenic trioxide combined with itraconazole can inhibit the KG1a cell proliferation and induce apoptosis, which may be related with the inhibition of Hh signaling pathway and upregulation of both Caspase-3 and BAX protein expression, and provided experimental data of arsenic trioxide combined with itraconazole for the treatment of refractory AML.

In order to further clarify the rational use of different medicinal parts of Schizonepeta, microfluidic technology was used in this study to investigate the differences in drug efficacy against lung cancer in vitro. The ethanol extracts were examined with HPLC to establish their fingerprints in order to analyze the relationship between the spectrum and efficacy index through Grey Correlation software, and a rapid HPLC-Q-TOF/MS method was established. The result in vitro shows that the effect and components of different medicinal parts had a certain differences, and apoptosis and necrosis rate from big to small in turn is leaf, flower, root, stem. The chromatographic peaks of the 26, 12, 2, 6 and 15th are the luteolin, icynaroside, rosmarinic, caffeic acid, and hesperidin, while the 20 and 10th may be dan phenolic acid L and benzoic acid. On the one hand, preliminary study reflects that the root of Schizonepeta tenuifolia may be developed into the medicinal parts in future. On the other hand, the major chemical composition of S. tenuifolia was found to have the anti-lung-tumor effects. This new method was established for the quality control and the rational use of different parts of traditional Chinese medicine.

In this paper, the modes of occurrence of the trace elements of Na, K, Fe and Si in SX-Coal and SD-Coal, which were used for COREX process, were analyzed. The coal was treated by wet digestion method and then the content of trace elements was analyzed. After that, the modes of occurrence of the elements were studied by sequential extraction procedure method and analyzed by ICP-OES. The results showed that the content of Na element is the highest and the content of K and Si elements is very low among the four elements in both kinds of coal. Na and K elements mainly exist in the mode of residue in SX-Coal and SD-Coal, and they are tends to enriched in the residue during the pyrolysis. Fe and Si elements mainly exist in the mode of carbonate, iron oxides and manganese oxides in SD-Coal. Fe and Si are tends to be decomposed from the compounds during the pyrolysis.

Low response, treatment-related complications and relapse due to the low sensitivity of myelodysplastic syndrome (MDS) and leukemia stem cells (LSCs) or pre‑LSCs to arsenic trioxide (ATO), represent the main problems following treatment with ATO alone in patients with MDS. To solve these problems, a chemosensitization agent can be applied to increase the susceptibility of these cells to ATO. Curcumin (CUR), which possesses a wide range of anticancer activities, is a commonly used chemosensitization agent for various types of tumors, including hematopoietic malignancies. In the present study, we investigated the cytotoxic effects and potential mechanisms in MDS-SKM-1 and leukemia stem-like KG1a cells treated with CUR and ATO alone or in combination. CUR and ATO exhibited growth inhibition detected by MTT assays and apoptosis analyzed by Annexin V/PI analyses in both SKM-1 and KG1a cells. Apoptosis of SKM-1 and KG1a cells determined by Annexin V/PI was significantly enhanced in the combination groups compared with the groups treated with either agent alone. Further evaluation was performed by western blotting for two hallmark markers of apoptosis, caspase-3 and cleaved-PARP. Co-treatment of the cells with CUR and ATO resulted in significant synergistic effects. In SKM-1 and KG1a cells, 31 and 13 proteins analyzed by protein array assays were modulated, respectively. Notably, survivin protein expression levels were downregulated in both cell lines treated with CUR alone and in combination with ATO, particularly in the latter case. Susceptibility to apoptosis was significantly increased in SKM-1 and KG1a cells treated with siRNA-survivin and ATO. These results suggested that CUR increased the sensitivity of SKM-1 and KG1a cells to ATO by downregulating the expression of survivin.

Leukemia relapse and nonrecurrence mortality (NRM) due to leukemia stem cells (LSCs) represent major problems following hematopoietic stem cell transplantation (HSCT). To eliminate LSCs, the sensitivity of LSCs to chemotherapeutic agents used in conditioning regimens should be enhanced. Curcumin (CUR) has received considerable attention as a result of its anticancer activity in leukemia and solid tumors. In this study, we investigated the cytotoxic effects and underlying mechanisms in leukemia stem-like KG1a cells exposed to busulfan (BUS) and CUR, either alone or in combination. KG1a cells exhibiting BUS-resistance demonstrated by MTT and annexin V/propidium iodide (PI) assays, compared with HL-60 cells. CUR induced cell growth inhibition and apoptosis in KG1a cells. Apoptosis of KG1a cells was significantly enhanced by treatment with CUR+BUS, compared with either agent alone. CUR synergistically enhanced the cytotoxic effect of BUS. Seven apoptosis-related proteins were modulated in CUR- and CUR+BUS-treated cells analyzed by proteins array analysis. Importantly, the antiapoptosis protein survivin was significantly downregulated, especially in combination group. Suppression of survivin with specific inhibitor YM155 significantly increased the susceptibility of KG1a cells to BUS. These results demonstrated that CUR could increase the sensitivity of leukemia stem-like KG1a cells to BUS by downregulating the expression of survivin.

This study was aimed to investigate the effect of Honokiol (HNK) on proliferation and apoptosis of acute myeloid leukemia HL-60 cells and its potential mechanism. Inhibitory effect of HNK on the HL-60 cell proliferation was detected by MTT assay. Flow cytometry was used to detect the change of cell cycle and AnnexinV/PI staining was used to detect apoptosis. Western blot was applied to analyze the cell cycle protein (cyclins), cyclin-dependent kinase (CDK), P53, P21, P27, BCL-2, BCL-XL, Bax, caspase-3/9 and proteins for MAPK signal pathway. The results showed that HNK could inhibit the proliferation of HL-60 cells in time- and dose dependent ways. HNK arrested HL-60 cells in G0/G1 phase, and S phase cells decreased significantly (P0.05). The expression of cyclin D1, cyclin A, cyclin E and CDK2/4/6 were significantly down-regulated (P0.05), the expression of P53 and P21 was significantly upregulated after treating for 24 h with HNK (P0.05). After 24 h treatment with HNK, HL-60 cell apoptosis increased significantly with the upregulation of activated caspase-3, -9, BAX expression and the downregulation of BCL-2, BCL-XL expression. The MAPK subfamily, P38 and JNK were not significantly changed, but the expression of MEK1/2-ERK1/2 was significantly downregulated (P0.05). It is concluded that HNK arrestes the cells at G0/G1 phase and induces HL-60 cell apoptosis through the intervention of MEK1/2-ERK1/2 signaling pathway.

This study was aimed to explore the effect of arsenic trioxide combined with curcumin on proliferation and apoptosis of KG1a cells and its potential mechanism. The cell survival rate was mesured by MTT; colony formation capacity was examined by methylcellulose colony formation test; flow cytometry was used to analyse the cell surface molecules, cell apoptosis rate and cell cycle; the cell morphology was observed with Wright-Giemsa staining and the protein expression of BCL-2, BAX, PARP was detected by Western blot. The results showed that the phenotype of KG1a cells was CD34(+)CD38(-), while the phenotype of HL-60 cell was CD34(+)CD38(+). The former possessed a stronger colony ability than the latter. Effect of curcumin and arsenic trioxide alone on cell proliferation and inhibition was in dose-dependent manner. Compared with single drug-treatment group, the cell survival rate and colony number were lower, and the apoptosis rate was higher in combined drug-treatment group. Protein expression of BCL-2 and PARP was upregulated, while the protein expression of PARP was downregulated in the combined treatment group. It is concluded that compared with HL-60 cells, KG1a cells are the earlier leukemia stem/progenitor cells. Arsenic trioxide combined with curcumin can effectively inhibit the KG1a cell proliferation and induce apoptosis, which may be associated with the downregulation of BCL-2 and PARP protein expression and the upregulation of BAX protein expression.

This study was aimed to investigate the effect of Honokiol (HNK) combined with Gemcitabine (GEM) on the proliferation and apoptosis of human Burkitt lymphoma Raji cells. Cell proliferation was detected by CCK-8 method to study the role of Honokiol and Gemcitabine in Raji cells. The cell apoptosis and cell cycle status were analyzed by flow cytometry. The level of apoptosis-related protein BCL-2 was measured with Western blot. The results showed that compared with cells treated with mentioned above drugs alone, the proliferative potential of cells in combination group was significantly inhibited (P0.01) and the inhibition rate was related to the concentration and action time of HNK; and apoptosis rate markedly increased (P0.01), while most Raji cells were arrested at G0/G1 phase and decreased in S phase after treatment with combination of two drugs; the expression of BCL-2 protein decreased (P0.01). It is concluded that Honokiol combined Gemcitabine can synergistically inhibit the proliferation, induce cell apoptosis, and down-regulate the expression of BCL-2 in Raji cells. The possible mechanism of synergistic effect may be related with arrest of cell cycle at G0/G1 phase and downregulation of the expression of BCL-2.