The combined enhancement of RL, nZVI and AQDS on the microbial anaerobic-aerobic degradation of PAHs in soil.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous persistent organic pollutants in soil, which have carcinogenic, teratogenic and mutagenic hazards. The effects of rhamnolipid (RL), nano zero-valent iron (nZVI), and anthraquinone-2,6-disulfonic acid (AQDS) on the degradation of PAHs in soil were studied. It was found that the treatment of 5 mg·kg-1RL + 1% nZVI +0.2 mmol·kg-1AQDS had the highest degradation rate. The degradation rate of total PAHs and HMW-PAHs was 72.81% and 79.47% respectively after 90 days. High-throughput sequencing showed that in RL + nZVI + AQDS enhanced soil, Clostridium, Geobacter, Anaeromyxobacter and Sphingomonas were the dominant species for anaerobic degradation of PAHs. Rhodococcus, Nocardioides, and Microvirga are the dominant species for aerobic degradation of PAHs. The activities of methyltransferase, dehydrogenase and catechol 1,2-dioxygenase in the anaerobic-aerobic degradation process of PAHs were consistent with the degradation process of PAHs, indicating the role of these enzymes in the degradation of PAHs. RL, nZVI, and AQDS combined enhanced microbial anaerobic-aerobic degradation has great application potential in remediation of PAHs-contaminated soil.

Bcl2 inhibitor ABT737 reverses the Warburg effect via the Sirt3-HIF1α axis to promote oxidative stress-induced apoptosis in ovarian cancer cells.

AIMS: Compared to normal cells, tumor cells maintain higher concentrations of reactive oxygen species (ROS) to support proliferation, invasion, and metastasis. Chemotherapeutic drugs often induce tumor cell apoptosis by increasing intracellular ROS concentrations to highly toxic levels. ABT737, which inhibits the apoptosis regulator B cell lymphoma 2 (Bcl2), increases the sensitivity of ovarian cancer cells to chemotherapeutic drugs by regulating the glucose metabolism, but the underlying mechanisms remain unclear. Therefore, we aimed to determine whether ABT737 promoted H2O2-induced tumor cell apoptosis by reversing glycolysis in ovarian cancer cells. MAIN METHODS: SKOV3 ovarian cancer cells were treated with H2O2, ABT737, or both. Cell viability was compared using methyl thiazolyl tetrazolium (MTT), and flow cytometry was used to detect differences in apoptosis, ROS, and mitochondrial membrane potential. The relative expression levels of proteins associated with apoptosis and the glucose metabolism were measured using immunoblotting. Finally, glucose uptake and lactate secretion were measured using kits and compared. KEY FINDINGS: ABT737 downregulated proteins associated with glucose uptake (GLUT1) and glycolysis (LHDA, PKM2 and HK2) via the Sirt3-HIF1α axis, reducing glucose uptake and lactate secretion in SKOV3 cells. This reversed glycolysis in the tumor cells, and promoted H2O2-induced apoptosis. SIGNIFICANCE: The Bcl2 inhibitor ABT737 enhanced the anti-tumor effect of oxidative stress by reversing the Warburg effect in ovarian cancer cells, providing powerful theoretical support for further clinical applications of Bcl2 inhibitors.

Dichloroacetic acid upregulates apoptosis of ovarian cancer cells by regulating mitochondrial function.

BACKGROUND: Metabolic reprogramming is a characteristic of tumor cells and is considered a potential therapeutic target. Even under aerobic conditions, tumor cells use glycolysis to produce energy, a phenomenon called the "Warburg effect". Pyruvate dehydrogenase kinase 1 (PDK1) is a key factor linking glycolysis and the tricarboxylic acid cycle. Dichloroacetic acid (DCA) reverses the Warburg effect by inhibition of PDK1 to switch cytoplasmic glucose metabolism to mitochondrial oxidative phosphorylation (OXPHOS). METHODS: Cell viability was examined using a standard MTT assay. Glucose consumption and l-lactate production were measured using commercial colorimetric kits, and intracellular lactate dehydrogenase (LDH) activity was evaluated using cell lysates and an LDH Quantification Kit. Real-time PCR was used to detect the expression of related genes. The production of total ROS was evaluated by staining with dichlorofluorescin diacetate. RESULTS: Comparison of various aspects of glucose metabolism, such as expression of key enzymes in glycolysis, lactate production, glucose consumption, mitochondrial oxygen consumption rate, and citric acid production, revealed that A2780/DDP cells were primarily dependent on glycolysis whereas A2780 cells were primarily dependent on mitochondrial OXPHOS. Mitochondrial uncoupling protein 2 (UCP2) protects against mitochondrial ROS while allowing energy metabolism to switch to glycolysis. Treatment of A2780 cells with various concentrations of DCA resulted in decreased expression of UCP2, a metabolic switch from glycolysis to mitochondrial OXPHOS, and an increase in oxidative stress induced by ROS. These effects were not observed in A2780/DDP cells with higher UCP2 expression suggesting that UCP2 might induce changes in mitochondrial functions that result in different sensitivities to DCA. CONCLUSION: Our results show that a drug targeting tumor metabolic changes affects almost the entire process of glucose metabolism. Thus, it is necessary to comprehensively determine tumor metabolic functions to facilitate individualized antitumor therapy.

Aneurysmal bone cyst on the left zygomatic arch concomitant with bilateral inferior turbinate gasification in an adult female: A case report.

The simultaneous occurrence of an aneurysmal bone cyst (ABC) on a zygomatic arch with bilateral inferior turbinate gasification is extremely rare, and no previous studies are available. Here we report the case of a 34-year-old Chinese Han female who presented with hyperplasia of the left maxillary bone for one and a half years. The patient was observed to have an ABC on the left zygomatic arch concomitant with bilateral inferior turbinate gasification, as indicated by X-ray computed tomography, contrast-enhanced computed tomography and three-dimensional maxillofacial reconstruction. The patient underwent surgical resection of the cyst, and no postoperative symptoms were observed during the 4 years of follow-up. The etiology of this case is considered to be associated with a gene abnormality.

[Effects of ovarian carcinoma cells on the maturation and function of human dendritic cells].

OBJECTIVE: To investigate the effects of ovarian carcinoma cells on the differentiation, maturation, and function of the dendritic cells (DC). METHODS: Human epithelial ovarian carcinoma cells were isolated from specimens of ovarian carcinoma from 12 patients obtained during operation, and cultured. Peripheral blood samples were collected from these patients. DC were isolated and co-cultured with recombinant human tumor necrosis factor (TNF)-alpha to promote their maturation. Immunostaining and flow cytometry (FC) were used to detect the DC specific marker CD1a, maturation marker CD83, co-stimulating factors CD86 and human leucocyte antigen (HLA)-DR. FITC-labeled glucan was added and FC was used to detect the phagocytic function. T cells were co-cultured with immature and mature DC of different concentrations respectively for 96 h, 18 h before the end of culture 3H-TdR was added, liquid scintillation counter was used to measure the level of count per minute (cpm) Ovarian carcinoma cells and peripheral mononuclear cells were put into Transwell to contact each other directly or indirectly, TNF-alpha was add to promote the maturation, and then FC was used to detect the CD1a, CD83, CD86, and HLA-DR levels, and the glucan uptake level. ELISA was used to detect the levels of IL-12, IL-10, and interferon (IFN)-gamma, and Western blotting was used to detect the p-38 protein and phosphorylated p-38 protein in the supernatant. RESULTS: After stimulation of TNF-alpha the expression; levels of CD1a, CD86, CD83, and HLA-DR of the DCs were remarkably increased. Immature DCs showed a strong ability at phagocytosis of glucan, and this ability was decreased by the stimulation of TNF-alpha. The proliferative function of mature DCs on allogenic T lymphocytes was significantly increased dose-dependently (P<0.05). Co-culture with ovarian carcinoma cells decreased the expression levels of CD1a, CD86, and HLA-DR, increased the expression level of CD83, and decreased the ability in up taking glucan by 43.05%. The proliferative function of the DC cultured in direct contact with ovarian carcinoma cells was decreased by 56.35%, and such inhibitory function of the DCs cultured not in direct contact with ovarian carcinoma cells was weaker, and the levels of CD1a, CD86, CD83, and HLA-DR expressed by the DC cultured not in direct contact with ovarian carcinoma cells was between those of the DC cultured in direct contact with ovarian carcinoma cells and those of the DC undergoing routine culture. The levels of IL-12 and phosphorylated p-38 protein were decreased in the supernatant of the DC co-cultured with ovarian carcinoma cells. CONCLUSION: Ovarian carcinoma cells suppress the differentiation of monocyte into DC, negatively regulates the phagocytotic and antaean managing functions of DC, thus the DC can not effectively stimulate the proliferation of T lymphocytes and inhibit the activity of cytotoxic T lymphocytes. That may be one of the underlying mechanisms of immune escape of tumor and immune tolerance of T lymphocytes.

[Simulated uterus microenvironment induced human placental mesenchymal stem cells differentiation to uterus smooth muscle cells in vitro].

OBJECTIVE: To develop a new method to promote the differentiation of mesenchymal stem cells derived from human placenta (pMSC) to uterus smooth muscle cells (uSMC) in simulated uterus microenvironment. METHODS: MSCs were isolated from human placenta, cultivated, and analyzed for their phenotype by flow cytometry. The multipotential differentiation of the pMSC was examined by chondrogenic, adipogenic, and osteogenetic induction. uSMC were isolated from uteri resected during operation and co-cultivated with the pMSC in a Transwell chamber simulating Two, 4, and 8 days later RT-PCR and Western blotting were used to detect the mRNA and protein expression of alpha-actin, calmodulin, and myosin heavy chains (MHC), the markers of smooth muscle differentiation at the early, middle, and late stages. On day 8 RT-PCR was used to detect the expression of estrogen receptor in these 2 groups of cells, then estrogen was used to stimulate these cells and the protein kinase C (PKC) activity was examined. RESULTS: The pMSC could be induced into adipocytes, osteocytes, and chondrocytes respectively. After co-culture with uSMC, the morphology of the pMSC changed closely into that of the uSMC, and MHC was expressed in the pMSC. Estrogen receptor was positive in both groups of cells. The PKC activity increased, especially in the cell membrane, after stimulation of estrogen. CONCLUSION: The postpartum human placenta can be used as an important and novel source of multipotent stem cells for tissue engineering and genetic engineering. Placental MSC have the potential to differentiate into smooth muscle cells under the simulated uterus microenvironment in vitro.