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The solubility of bisphenol A in 14 different pure solvents (N,N-dimethylformamide, formamide, acetone, 1,4-dioxane, cyclohexanone, ethyl acetate, methyl acetate, acetonitrile, ethanol, methanol, 1...

The solubility of methyleneaminoacetonitrile in binary (ethanol+water, ethanol+2-propanol, ethanol+ n -butanol) solvents was measured by a laser dynamic method under p = 101.1 kPa at temperatures ranging from 278.15 K to 323.15 K. The solubility increased with increasing temperature at a given solvent composition; the solubility also increased with the increasing content of ethanol at a given temperature. The modified Apelblat equation, λh equation and Jouyban-Acree model were used to correlate the experimental solubility data, the values of RD and RMSD indicated that these models fit solubility data well. The calculated thermodynamic properties of Δ sol H ° , Δ sol S ° , Δ sol G ° showed that the dissolution process in binary solvents was endothermic and entropy-driven.

The solubility of methyleneaminoacetonitrile in binary solvents (ethanol+methanol, 2-propanol+methanol, n‑butanol+methanol) was measured by a laser dynamic method under atmospheric pressure at temperatures ranging from 278.15 K to 323.15 K. The solubility of methyleneaminoacetonitrile in binary solvents increased with increasing temperature and the content of methanol. In addition, Hansen solubility parameters (HSP) were used to explain and predict the solubility behavior. The experimental solubility data in binary solvents were correlated by the modified Apelblat equation, λh equation, Jouyban-Acree model, and Sun model. The values of RD and RMSD indicated that these models fit the solubility data well in binary solvents. The thermodynamic properties (ΔsolH°, ∆solS°, ∆solG°, %ξH, %ξTS) of the solution were calculated from the van't Hoff equation, and the dissolution process was endothermic, and the force of the dissolution process was entropy-driven.

The solubility of 2-cyanoacetamide in N,N-dimethylformamide, acetone, acetonitrile, methanol, methyl acetate, tetrahydrofuran, ethanol, ethyl acetate, n-propanol, n-butanol, trichloromethane, dichl...

Exposure to fine particulate matter (PM2.5) can induce oxidative stress and proinflammatory cytokine production, which are central for the induction of PM2.5-mediated adverse effects on public health. Nuclear factor kappa B (NF-κB) signaling is essential for inflammation. The subcellular distribution of thioredoxin (Trx) is related to the activation of NF-κB, but the mechanism involved is unclear. In the current study, we focused on the relationship between the antioxidant Trx and NF-κB in human bronchial epithelial cells (BEAS-2B) after PM2.5 exposure. We inhibited the nuclear translocation of Trx by cHCEU (4-cyclohexyl-[3-(2-chloroethyl)ureido]benzene) and subsequently increased the transcriptional activity of Nrf2 to upregulate the expression of Trx by t-BHQ. Our data suggest that PM2.5 exposure induces the activation of NF-κB and the expression of the downstream proinflammatory cytokines IL-1, IL-6, IL-8 and TNF-α in BEAS-2B cells. CHCEU alleviates inflammatory cytokines by blocking Trx nuclear translocation and inhibits the DNA binding activity of NF-κB. T-BHQ could promote the transcriptional activity of Nrf2 but failed to alleviate the production of inflammatory cytokines. Furthermore, the synergistic effect of t-BHQ and cHCEU on alleviating PM2.5-induced inflammation is more effective than the use of cHCEU alone. Our findings characterize the underlying molecular mechanisms of proinflammatory responses induced by PM2.5 and show that the nuclear translocation and accumulation of Trx in nuclei play important roles in PM2.5-induced NF-κB activation and proinflammatory responses.

Lung cancer is one of the most common human cancers. Long noncoding RNA AFAP1-AS1 (LncRNA AFAP1-AS1) and microRNA-545-3p (miR-545-3p) were reported to play important roles in lung cancer development. This study aimed to elucidate the functional mechanisms of AFAP1-AS1 and miR-545-3p in lung cancer. Quantitative real time polymerase chain reaction was carried out to determine the levels of AFAP1-AS1, miR-545-3p and hepatoma-derived growth factor (HDGF). Cell proliferation, apoptosis, migration and invasion were detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide assay, flow cytometry, and transwell migration and invasion assays, respectively. Furthermore, the interaction between miR-545-3p and AFAP1-AS1 or HDGF was predicted by bioinformatics analysis software starbase and confirmed by the dual luciferase reporter assay. Western blot assay was used to detect the protein level of HDGF. Besides, murine xenograft model was conducted through injecting A549 cells transfected with sh-AFAP1-AS1. The expression levels of AFAP1-AS1 and HDGF were increased, while miR-545-3p was decreased in lung cancer tissues and cells. AFAP1-AS1 knockdown suppressed lung cancer cell proliferation, migration, and invasion and induced apoptosis. Furthermore, AFAP1-AS1 mediated cell progression through regulating miR-545-3p expression. In addition, miR-545-3p negatively regulated the expression level of HDGF via binding 3'-untranslated region of HDGF. As expected, AFAP1-AS1 knockdown inhibited lung cancer progression via affecting miR-545-3p/HDGF axis. Besides, AFAP1-AS1 knockdown suppressed lung cancer tumor growth in vivo. Collectively, our results suggested that AFAP1-AS1 promoted the development of lung cancer via regulating miR-545-3p/HDGF axis, providing a potential target for the treatment of lung cancer.

In this study, RGD coated GEM liposomes were prepared by the emulsification-solvent evaporation method. The in vitro and in vivo characterizations were done to evaluate the feasibility of applicati...

We tested the hypothesis that oral NaHCO3 intake stimulates splenic anti-inflammatory pathways. Following oral NaHCO3 loading, macrophage polarization was shifted from predominantly M1 (inflammatory) to M2 (regulatory) phenotypes, and FOXP3+CD4+ T-lymphocytes increased in the spleen, blood, and kidneys of rats. Similar anti-inflammatory changes in macrophage polarization were observed in the blood of human subjects following NaHCO3 ingestion. Surprisingly, we found that gentle manipulation to visualize the spleen at midline during surgical laparotomy (sham splenectomy) was sufficient to abolish the response in rats and resulted in hypertrophy/hyperplasia of the capsular mesothelial cells. Thin collagenous connections lined by mesothelial cells were found to connect to the capsular mesothelium. Mesothelial cells in these connections stained positive for the pan-neuronal marker PGP9.5 and acetylcholine esterase and contained many ultrastructural elements, which visually resembled neuronal structures. Both disruption of the fragile mesothelial connections or transection of the vagal nerves resulted in the loss of capsular mesothelial acetylcholine esterase staining and reduced splenic mass. Our data indicate that oral NaHCO3 activates a splenic anti-inflammatory pathway and provides evidence that the signals that mediate this response are transmitted to the spleen via a novel neuronal-like function of mesothelial cells.

Silicosis is pathologically characterized by diffused pulmonary fibrosis and abundant deposition of extracellular matrix (ECM) components. The ECM is mainly secreted by myofibroblasts which are the activated state of fibroblasts. MicroRNA-29b (miR-29b) is one of the well-known microRNAs involved in fibrosis, but its roles in silicosis have not been specified. In this study, we hypothesized that miR-29b might play a protective role in the progression of silicosis. MTT assay, qRT-PCR, immunofluorescence and western blotting were applied. The results demonstrated that the supernatants from silica-treated macrophages not only caused the proliferation of fibroblasts (NIH-3T3 and MRC-5) but were also involved in the down-regulation of miR-29b. Meanwhile they could induce fibroblast activation, increasing the expression of ECM components such as collagen1 and collagen3, in a silica dose-dependent manner. Furthermore, overexpression of miR-29b by transfecting mimics markedly reduced the expression of ECM components and inhibited ECM synthesis. These findings indicate that miR-29b inhibits the supernatants from silica-treated macrophages from inducing extracellular matrix synthesis, thus miR-29b might have a strong anti-fibrotic capacity in silicosis and serve as a potential therapeutic agent for the treatment.

Hv1 is a voltage-gated proton channel highly expressed in immune cells where, it acts to maintain NAD(P)H oxidase activity during the respiratory burst. We have recently reported that Hv1 is expressed in cells of the medullary thick ascending limb (mTAL) of the kidney and is critical to augment reactive oxygen species (ROS) production by this segment. While Hv1 is associated with NOX2 mediated ROS production in immune cells, the source of the Hv1 dependent ROS in mTAL remains unknown. In the current study, the rate of ROS formation was quantified in freshly isolated mTAL using dihydroethidium and ethidium fluorescence. Hv1 dependent ROS production was stimulated by increasing bath osmolality and ammonium chloride (NH4Cl) loading. Loss of either p67phox or NOX4 did not abolish the formation of ROS in mTAL. Hv1 was localized to mitochondria within mTAL, and the mitochondrial superoxide scavenger mitoTEMPOL reduced ROS formation. Rotenone significantly increased ROS formation and decreased mitochondrial membrane potential in mTAL from wild-type rats, while treatment with this inhibitor decreased ROS formation and increased mitochondrial membrane potential in mTAL from Hv1−/− mutant rats. These data indicate that NADPH oxidase is not the primary source of Hv1 dependent ROS production in mTAL. Rather Hv1 localizes to the mitochondria in mTAL and modulates the formation of ROS by complex I. These data provide a potential explanation for the effects of Hv1 on ROS production in cells independent of its contribution to maintenance of cell membrane potential and intracellular pH., Graphical abstract Image 1

The design and synthesis of highly active adsorption materials for recycling noble metals are essential to the high-tech industry. Here, a new adsorbent material namely resorcinol-formaldehyde-biuret (RFB) is prepared by grafting biuret onto the phenolic. Compared with the traditional methods, the preparation of RFB herein requires no hydrothermal process, which reduces cost. What's more, RFB prepared without the hydrothermal process exhibits better adsorption performance. Specifically, it has a high adsorption capacity of 1334 mg/g at room temperature and a fast adsorption rate that can adsorb a 10 mL of 100 mg/L gold ion solution within 10 min by just 5 mg RFB. Different factors such as pH, coexisting metal ions, and contact time that affects the adsorption process were systematically investigated. FT-IR, SEM, TEM, and XPS were used to characterize the adsorbent before and after adsorption. It is found that the adsorption isotherm and kinetics of RFB are consistent with the Langmuir isotherm model and the pseudo-second-order kinetic model, respectively. Further regeneration and cyclic adsorption indicate that RFB can be recycled at least four times. Besides, the reduction of 4-nitrophenol to 4-aminophenol was realized with the assist of Au-adsorbed RFB (RFB-Au). The strong soft-soft interaction between N, O atoms and Au atoms gives the material excellent gold ion adsorption capacity and selectivity. Findings herein can broaden the application of nitrogen-rich nanomaterials in gold ion recovery.

The N-doped mesoporous carbon materials (CNM) had been synthesized with hard template method. Benzoxazine (BOZ) was adopted as a precursor and SBA-15 as template. The electrochemical performance of carbon materials prepared by different ultrasonic time, different benzoxazine concentration and different carbonization temperature were conducted by a three-electrode system. In order to further explain electrochemical behaviour of the obtained carbon materials, the corresponding characterizations were also done. CNM-800 had a highest specific capacitance value, 428.8 F g−1 (0.25 A/g) in the three-electrode system. After 20,000 cycles of CNM-800 at the current density of 5 A g−1, CNM-800 still had 98.5% of the original capacitance, which showed that CNM-800 had a good cycling stability. In order to investigate the application value of supercapacitors, a two-electrode system was also adopted, a maximum energy density was 11.2 Wh kg−1. The prepared carbon material (CNM-800) have the higher specific capacitance than the related literatures. This kind of N-doped mesoporous carbon material would have a potential application value as supercapacitor.

Sodium bicarbonate (NaHCO3) slows the decline in kidney function in patients with chronic kidney disease (CKD), yet the mechanisms mediating this effect remain unclear. The Dahl salt-sensitive (SS) rat develops hypertension and progressive renal injury when fed a high salt diet; however, the effect of alkali loading on kidney injury has never been investigated in this model. We hypothesized that NaHCO3 protects from the development of renal injury in Dahl salt-sensitive rats via luminal alkalization which limits the formation of tubular casts, which are a prominent pathological feature in this model. To examine this hypothesis, we determined blood pressure and renal injury responses in Dahl SS rats drinking vehicle (0.1 M NaCl) or NaHCO3 (0.1 M) solutions as well as in Dahl SS rats lacking the voltage-gated proton channel (Hv1). We found that oral NaHCO3 reduced tubular NH4+ production, tubular cast formation, and interstitial fibrosis in rats fed a high salt diet for 2 weeks. This effect was independent of changes in blood pressure, glomerular injury, or proteinuria and did not associate with changes in renal inflammatory status. We found that null mutation of Hv1 also limited cast formation in Dahl SS rats independent of proteinuria or glomerular injury. As Hv1 is localized to the luminal membrane of TAL, our data suggest that alkalization of the luminal fluid within this segment limits cast formation in this model. Reduced cast formation, secondary to luminal alkalization within TAL segments may mediate some of the protective effects of alkali loading observed in CKD patients.

Hv1 is a voltage-gated proton channel highly expressed in phagocytic cells, where it participates in the NADPH oxidase-dependent respiratory burst. We have recently identified Hv1 as a novel renal channel, expressed in the renal medullary thick ascending limb that appears to importantly contribute to the pathogenesis of renal hypertensive injury in the Dahl salt-sensitive rat model. The purpose of this review is to describe the experimental approaches that we have undertaken to identify the source of excess reactive oxygen species production in the renal outer medulla of Dahl salt-sensitive rats and the resulting evidence that the voltage-gated proton channel Hv1 mediates augmented superoxide production and contributes to renal medullary oxidative stress and renal injury. In addition, we will attempt to point out areas of current controversy, as well as propose areas in which further experimental studies are likely to move the field forward. The content of the following review was presented as part of the Water and Electrolyte Homeostasis Section New Investigator Award talk at Experimental Biology 2014.

This study examined the ability of plumbagin to induce apoptosis in chronic myelogenous leukemia (CML). Plumbagin exposure led to a significant reduction in cell viability and the induction of apoptosis. Mechanistically, plumbagin treatment led to elevated levels of ROS. Plumbagin-induced apoptosis was inhibited by N-acetyl L-cysteine (NAC) and PEG-catalase. Furthermore, plumbagin exposure led to elevated expression of DR4 and DR5 and increased killing through soluble TRAIL. The plumbagin-induced increase in DR4 and DR5 was inhibited by treatment with NAC. Together, this study suggests that plumbagin may be an effective treatment of CML through increased sensitivity to TRAIL-mediated killing.

Extracts from plants containing plumbagin (PLB) continue to be used as a treatment of a number of chronic immunologically-based diseases. However, most of these claims are supported only by anecdotal evidence with few scientific reports describing the mechanism of action or the efficacy of plumbagin in the suppression of the immune response. In the current study, we tested the hypothesis that plumbagin-induced suppression of the immune response was mediated through the induction of apoptosis. Splenocytes from C57BL/6 mice cultured in the presence of 0.5 mu M or greater concentrations of PLB significantly reduced proliferative responses to mitogens, including anti-CD3 mAbs, concanavalin A (Con A), lipopolysaccharide (LPS) and staphylococcal enterotoxin B (SEB) in vitro. Exposure of naive and activated splenocytes to PLO led to a significant increase in the levels of apoptosis. In addition, PLB treatment led to a significant increase in the levels of reactive oxygen species (ROS) in naive and activated splenocytes. Furthermore, treatment with the ROS scavenger, N-acetylcysteine (NAC), prevented PLB-induced apoptosis, suggesting a role of ROS in PLO-induced apoptosis. PLB-induced apoptosis led to ROS-mediated activation of both the extrinsic and intrinsic apoptotic pathways. In addition, plumbagin led to increased expression of Fas. Finally, treatment of mice with PLO (5 mg/kg) led to thymic and splenic atrophy as well as a significant suppression of the response to SEB and dinitroflourobenzene (DNFB) in vivo. Together, these results suggest that plumbagin has significant immunosuppressive properties which are mediated by generation of ROS, upregulation of Fas, and the induction of apoptosis. (C) 2010 Elsevier Inc. All rights reserved.

In postmenopausal women, human 3beta-hydroxysteroid dehydrogenase type 1 (3beta-HSD1) is a critical enzyme in the conversion of DHEA to estradiol in breast tumors, while 3beta-HSD2 participates in the production of cortisol and aldosterone in the human adrenal gland. The goals of this project are to determine if Arg195 in 3beta-HSD1 vs. Pro195 in 3beta-HSD2 in the substrate/inhibitor binding site is a critical structural difference responsible for the higher affinity of 3beta-HSD1 for inhibitor and substrate steroids compared to 3beta-HSD2 and whether Asp61, Glu192 and Thr8 are fingerprint residues for cofactor and substrate binding using site-directed mutagenesis. The R195P-1 mutant of 3beta-HSD1 and the P195R-2 mutant of 3beta-HSD2 have been created, expressed, purified and characterized kinetically. Dixon analyses of the inhibition of the R195P-1 mutant, P195R-2 mutant, wild-type 3beta-HSD1 and wild-type 3beta-HSD2 by trilostane has produced kinetic profiles that show inhibition of 3beta-HSD1 by trilostane (K(i)=0.10microM, competitive) with a 16-fold lower K(i) and different mode than measured for 3beta-HSD2 (K(i)=1.60microM, noncompetitive). The R195P-1 mutation shifts the high-affinity, competitive inhibition profile of 3beta-HSD1 to a low-affinity (trilostane K(i)=2.56microM), noncompetitive inhibition profile similar to that of 3beta-HSD2 containing Pro195. The P195R-2 mutation shifts the low-affinity, noncompetitive inhibition profile of 3beta-HSD2 to a high-affinity (trilostane K(i)=0.19microM), competitive inhibition profile similar to that of 3beta-HSD1 containing Arg195. Michaelis-Menten kinetics for DHEA, 16beta-hydroxy-DHEA and 16alpha-hydroxy-DHEA substrate utilization by the R195P-1 and P195R-2 enzymes provide further validation for higher affinity binding due to Arg195 in 3beta-HSD1. Comparisons of the Michaelis-Menten values of cofactor and substrate for the targeted mutants of 3beta-HSD1 (D61N, D61V, E192A, T8A) clarify the functions of these residues as well.

A three-stage hybrid membrane process for the concentration of ethanol–water extracts of the Echinacea plant has been investigated. Preliminary investigations using osmotic distillation in a single-stage process resulted in severe membrane wet-out by the ethanol-soluble, sparingly water-soluble alkyl amides that precipitated from solution due to the preferential removal of ethanol. In Stage 1 of the hybrid process, ethanol removal from the neat extract was achieved by pervaporation (PV). This gave an ethanol-free aqueous product containing suspended alkyl amides that was suitable for marketing in tincture form. In Stage 2, the precipitated alkyl amides were removed from the Stage 1 product by microfiltration (MF). In Stage 3, the microfiltration permeate was concentrated several-fold by osmotic distillation, followed by adding-back of the microfiltration retentate containing the precipitated alkyl amides to the osmotic distillation retentate. This gave a highly concentrated product suitable for marketing in capsule form. In addition to process design and product characterisation, pervaporation operating conditions were optimised for greatest efficiency in this application.

We previously characterized a H + transport pathway in medullary thick ascending limb nephron segments that when activated stimulated the production of superoxide by nicotinamide adenine dinucleotide phosphate oxidase. Importantly, the activity of this pathway was greater in Dahl salt-sensitive rats than salt-resistant (SS.13 BN ) rats, and superoxide production was enhanced in low Na + media. The goal of this study was to determine the molecular identity of this pathway and its relationship to Na + . We hypothesized that the voltage-gated proton channel, HV1, was the source of superoxide-stimulating H + currents. To test this hypothesis, we developed HV1 −/− null mutant rats on the Dahl salt-sensitive rat genetic background using zinc-finger nuclease gene targeting. HV1 could be detected in medullary thick limb from wild-type rats. Intracellular acidification using an NH 4 Cl prepulse in 0 sodium/BaCl 2 containing media resulted in superoxide production in thick limb from wild-type but not HV1 −/− rats ( P I 0.005 versus 0.002 U/s, P =0.046, respectively). Superoxide production was enhanced by low intracellular sodium (−/− rats compared with wild-type Dahl salt-sensitive rats. We conclude that HV1 is expressed in medullary thick ascending limb and promotes superoxide production in this segment when intracellular Na + is low. HV1 contributes to the development of hypertension and renal disease in Dahl salt-sensitive rats.

We have recently demonstrated that both cellular acidification and low intracellular [Na] promote NADPH oxidase activity in mTAL via activation of the voltage-gated proton channel Hv1. NH4+ is norm...

Oxidative stress in the renal outer-medulla contributes to the development of hypertension and renal disease in Dahl salt-sensitive (SS) rats. We have previously demonstrated that an unknown proton channel is responsible for enhanced superoxide production in medullary thick ascending limb (mTAL) of SS rats. We hypothesized that HV1 is responsible for superoxide producing H+ currents and is expressed in mTAL of SS rats. In order to test our hypothesis we quantitated HV1 mRNA (RT-PCR) and protein (immunohistochemistry) specifically within mTAL of wild-type SS rats and in a HV1-/- strain of Dahl SS rats in which we mutated the HV1 gene using a Zn-finger nuclease. We confirmed complete loss of Hv1 protein in HV1-/- rats both by whole-cell voltage clamp of peritoneal macrophages and by Western blot/anti-HV1 staining in spleen (positive control tissue). Using the same antibody, HV1 protein expression was found to be significantly greater in mTAL of wild-type rats compared to presumed background in HV1-/- rats (...

Human 3beta-hydroxysteroid dehydrogenase/isomerase type 1 (3beta-HSD1) is a critical enzyme in the conversion of DHEA to estradiol in breast tumors and may be a target enzyme for inhibition in the treatment of breast cancer in postmenopausal women. Human 3beta-HSD2 participates in the production of cortisol and aldosterone in the human adrenal gland in this population. In our recombinant human breast tumor MCF-7 Tet-off cells that express either 3beta-HSD1 or 3beta-HSD2, trilostane and epostane inhibit the DHEA-induced proliferation of MCF-7 3beta-HSD1 cells with 12- to 16-fold lower IC(50) values compared to the MCF-7 3beta-HSD2 cells. The compounds also competitively inhibit purified human 3beta-HSD1 with 12- to 16-fold lower K(i) values compared to the noncompetitive K(i) values measured for human 3beta-HSD2. Using our structural model of 3beta-HSD1, trilostane or 17beta-acetoxy-trilostane was docked in the active site of 3beta-HSD1, and Arg195 in 3beta-HSD1 or Pro195 in 3beta-HSD2 was identified as a potentially critical residue (one of 23 non-identical residues in the two isoenzymes). The P195R mutant of 3beta-HSD2 were created, expressed and purified. Kinetic analyses of enzyme inhibition suggest that the high affinity, competitive inhibition of 3beta-HSD1 by trilostane and epostane may be related to the presence of Arg195 in 3beta-HSD1 vs. Pro195 in 3beta-HSD2.