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Furosemide, abbreviated as FS, is a loop diuretic drug with low solubility and permeability. Herein, three adducts derived from FS and hexamethylenetetramine (HTEM), amantadine (AMD) and isonicotin...

Indomethacin (Indo) and naproxen (Nap) belong to Biopharmaceutical Classification System (BCS) class II drugs, which permeate membranes well but are poorly soluble. Two pharmaceutical salts hydrate of Indo and Nap with (1R,2R)-1,2-diphenylethylenediamine (DPEN) were obtained using solution crystallization. Both salts, (DPEN)2·(Indo)2·(H2O)2 and (DPEN)1·(Nap)1·(H2O)0.5, were characterised using various solid-state characterisation techniques such as single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and Raman spectra. The structure analysis shows that DPEN is monocation as only one amine is protonated into ammonium. The Indo, DPEN and water molecules form one-dimensional hydrogen bond chains through extensive N H⋯O, N H⋯N and O H⋯N interactions. The solubility study shows that the two salts are more soluble in pH 1.2, 4.5 and 6.8 buffer mediums compared with pure raw materials. Solubility thermodynamics calculation was carried out to further understand the solubility properties of two salts.

The aim of the present study was to investigate the effect of chitosan (a naturally derived polymer) on the immune responses and glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and lactate dehydrogenase (LDH) levels in WEHI-3 cell-generated leukemia mice. Mice were divided into control, WEHI-3 control, acetic acid (vehicle)-treated, and 5 and 20 mg/kg chitosan-treated groups. Mice were subsequently weighed, blood was collected, and liver and spleen samples were isolated and weighed. Blood samples were measured for cell markers, the spleen underwent phagocytosis and natural killer (NK) cell activity examination, and cell proliferation was analyzed by flow cytometry. Chitosan did not significantly affect the weights of body, liver and spleen at 5 and 20 mg/kg treatment. Chitosan increased the percentage of CD3 (T cells marker), decreased the levels of CD19 (B-cell marker) and CD11b at 5 mg/kg treatment, and decreased the levels of Mac-3 at 5 and 20 mg/kg treatment. Chitosan significantly increased macrophage phagocytosis of PBMCs, but did not significantly affect macrophage phagocytosis in the peritoneal cavity. Chitosan treatment did not significantly affect the cytotoxic activity of NK cells, and also did not affect T- and B-cell proliferation. Chitosan significantly increased total white blood cell numbers, and GOT and GPT activities were both significantly increased. However, chitosan did not significantly affect LDH activity in leukemia mice. Chitosan may aid in future studies on improving immune responses in the treatment of leukemia.

High dopant (phosphorus) activation of 24% and 27% in strained and relaxed Ge 0.93 Sn 0.07 films are demonstrated by microwave annealing, respectively. The annealing effects on the carrier activation in strained and relaxed GeSn films by RTA and MWA were also investigated.

The GeSn films were epitaxially grown by reduced pressure chemical vapor deposition and characterized by X-ray diffraction and reciprocal space mapping. By phosphorus implant with a dose of 2 x 1015 cm-2 followed by rapid thermal annealing at 550 °C, a Ge 0.93 Sn 0.07 n+/p diode with an extremely high I ON /I OFF ratio of 6 x 105 is demonstrated.

Sulforaphane (SFN), one of the isothiocyanates, is a biologically active compound extracted from cruciferous vegetables, and has been shown to induce cytotoxic effects on many human cancer cells including human leukemia cells. However, the exact molecular mechanism and altered gene expression associated with apoptosis is unclear. In this study, we investigated SFN-induced cytotoxic effects and whether or not they went through cell-cycle arrest and induction of apoptosis and further examined molecular mechanism and altered gene expression in human leukemia HL-60 cells. Cell viability, cell-cycle distribution, sub-G1 (apoptosis), reactive oxygen species (ROS) and Ca2+ production, levels of mitochondrial membrane potential (ΔΨm ), and caspase-3, -8, and -9 activities were assayed by flow cytometry. Apoptosis-associated proteins levels and gene expressions were examined by Western blotting and cDNA microarray assays, respectively. Results indicated that SFN decreased viable cells, induced G2/M phase arrest and apoptosis based on sub-G1 phase development. Furthermore, SFN increased ROS and Ca2+ production and decreased the levels of ΔΨm and activated caspase-3, -8, and -9 activities in HL-60 cells. SFN significantly upregulated the expression of BAX, Bid, Fas, Fas-L, caspase-8, Endo G, AIF, and cytochrome c, and inhibited the antiapoptotic proteins such as Bcl-x and XIAP, that is associated with apoptosis. We also used cDNA microarray to confirm several gene expressions such as caspase -8, -3, -4, -6, and -7 that are affected by SFN. Those results indicated that SFN induced apoptosis in HL-60 cells via Fas- and mitochondria-dependent pathways. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 311-328, 2017.

Background/aim Laminarin, a typical component of fungal cell walls, has been shown to induce immune responses in both adult and larval locusts. We investigated the effects of laminarin on immune response and glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and lactate dehydrogenase (LDH) levels in normal mice. Materials and methods Thirty-six normal BALB/c mice were randomly divided into four groups and treatments were provided by gavage. Group I mice acted as normal control; mice of groups II-IV received laminarin at different doses (100 μl at 1, 2.5 and 5.0 mg/mouse in double-distilled water, respectively). All animals were treated for 14 days and were weighed, blood was collected for determination of cell markers, liver and spleen samples were weighed. Spleens were used for phagocytosis and determination of natural killer (NK) cell activity and cell proliferation by flow cytometric assay. Results Laminarin reduced the body weights and weights of liver and spleen. Laminarin increased CD3, CD19 and Mac-3 cell populations at 2.5 and 5 mg/mouse, however, these did not affect CD11b marker levels. Laminarin (1 and 5 mg/mouse) reduced macrophage phagocytosis from peripheral blood mononuclear cells, but did not affect phagocytosis by macrophages from the peritoneal cavity. At an effector:target ratio of 50:1, laminarin reduced NK cell cytotoxic activity at all levels, but at a ratio of 25:1, only at 1 mg treatment. Laminarin did not affect T-cell and B-cell proliferation. Laminarin increased the level of GPT and reduced that of LDH at all doses, indicating laminarin can protect against liver injury. Laminarin is worthy of investigation in future experiments on improving immune responses.

Background/aim Antrodia cinnamomea is found with polysaccharides, lipids, vitamins, fibers and ash (minerals) and is well known in Taiwan as a traditional Chinese medicine. Its biological activities have been reported to have anti-inflammatory, anti-fatigue, anti-tumor and immunomodulatory effects, but its protective effects on liver function are still unclear. Materials and methods We determined if Antrodia cinnamomea was hepatoprotective against carbon tetrachloride (CCl4) toxicity in Wistar rats. Six groups were used in the study: 1) control (no induction by CCl4); 2) negative control (CCl4-induction and no treatment); 3) positive control (silymarin treatment); 4) groups 4-6 were treated with CC14 and different concentrations (350 mg/kg, 1,400 mg/kg, 3,150 mg/kg) of Antrodia cinnamomea. Blood and liver samples of rats were harvested and then detected by biochemical and tissue histochemical analysis. Activity of the antioxidative enzymes glutathione peroxidase, superoxide dismutase and catalase in the liver were also monitored. Results Only the high-dose treatment was able to decrease serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) levels and improve liver function. High and medium doses increased total liver protein and reduced hydroxyproline. It was also observed that the high dose treatment reduced lipid peroxidation. Liver sections of CC14 treated animals receiving Antrodia cinnamomea showed less fibrosis compared to the CCl4 control group. Conclusion This finding suggested that Antrodia cinnamomea can either enhance liver recovering from CCl4 damage or attenuate CCl4 toxicity in rats.

Boron (B) alleviates aluminum (Al) toxicity in higher plants; however, the underlying mechanisms behind this phenomenon remain unknown. Here, we used bromocresol green pH indicator, noninvasive microtest, and microelectrode ion flux estimation techniques to demonstrate that B promotes root surface pH gradients in pea (Pisum sativum) roots, leading to alkalization in the root transition zone and acidification in the elongation zone, while Al inhibits these pH gradients. B significantly decreased Al accumulation in the transition zone (∼1.0–2.5 mm from the apex) of lateral roots, thereby alleviating Al-induced inhibition of root elongation. Net indole acetic acid (IAA) efflux detected by an IAA-sensitive platinum microelectrode showed that polar auxin transport, which peaked in the root transition zone, was inhibited by Al toxicity, while it was partially recovered by B. Electrophysiological experiments using the Arabidopsis (Arabidopsis thaliana) auxin transporter mutants (auxin resistant1-7; pin-formed2 [pin2]) and the specific polar auxin transporter inhibitor1-naphthylphthalamic acid showed that PIN2-based polar auxin transport is involved in root surface alkalization in the transition zone. Our results suggest that B promotes polar auxin transport driven by the auxin efflux transporter PIN2 and leads to the downstream regulation of the plasma membrane-H+-ATPase, resulting in elevated root surface pH, which is essential to decrease Al accumulation in this Al-targeted apical root zone. These findings provide a mechanistic explanation for the role of exogenous B in alleviation of Al accumulation and toxicity in plants.

Background/aim Oral cancer has been reported to be one of the major cancer-related diseases in human populations and the treatment of oral cancer is still unsatisfied. Fisetin, is a flavonoid from plants and has several biological activities such as antioxidant, anti-inflammatory and anticancer function, but its cytotoxicity in human oral cancer cells is unknown. In the present study, we investigated fisetin-induced cytotoxic effects on HSC3 human oral cancer cells in vitro. Materials and Methods/Results: We used flow cytometric assay to show fisetin induced apoptotic cell death through increased reactive oxygen species and Ca2+, but reduced the mitochondrial membrane potential and increased caspase-8, -9 and -3 activities in HSC3 cells. Furthermore, we also used 4' 6-diamidino-2-phenylindole staining to show that fisetin induced chromatin condensation (apoptotic cell death), and Comet assay to show that fisetin induced DNA damage in HSC3 cells. Western blotting was used to examine the levels of apoptotic-associated protein and results indicated that fisetin increased expression of pro-apoptotic proteins such as B-cell lymphoma 2 (BCL2) antagonist/killer (BAK) and BCL2-associated X (BAX) but reduced that of anti-apoptotic protein such as BCL2 and BCL-x, and increased the cleaved forms of caspase-3, -8 and -9, and cytochrome c, apoptosis-inducing factor (AIF) and endonuclease G (ENDO G) in HSC3 cells. Confocal microscopy showed that fisetin increased the release of cytochrome c, AIF and ENDO G from mitochondria into the cytoplasm. Conclusion Based on these observations, we suggest that fisetin induces apoptotic cell death through endoplasmic reticulum stress- and mitochondria-dependent pathways.

ZnSn(OH)6hierarchical cubes and Zn2SnO4octahedra have been synthesized through a rapid, template-free, one-pot hydrothermal approach using zinc acetate, tin chloride and sodium hydroxide. ZnSn(OH)6aggregates with cubic morphology and uniform size distribution have been successfully synthesized via aggregation-mediated crystallization. Through adjusting the hydrothermal parameters, Zn2SnO4octahedra were obtained at a higher temperature. The formation of Zn2SnO4 octahedra undergone a transformation from ZnSn(OH)6cubes. The as-synthesized products were characterized by powder X-ray diffraction (XRD), scanning electron microscopy (SEM) and differential scanning calorimetric analysis (DSC) and thermogravimetric analysis (TG).

Chitosan, a naturally derived polymer, has been shown to possess antimicrobial and anti-inflammatory properties; however, little is known about the effect of chitosan on the immune responses and glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and lactate dehydrogenase (LDH) activities in normal mice. The aim of the present study was to investigate whether chitosan has an effect on the immune responses and GOT, GPT and LDH activities in mice in vivo. BALB/c mice were divided into four groups. The negative control group was treated with a normal diet; the positive control group was treated with a normal diet plus orally administered acetic acid and two treatment groups were treated with a normal diet plus orally administered chitosan in acetic acid at doses of 5 and 20 mg/kg, respectively, every other day for 24 days. Mice were weighed during the treatment, and following the treatment, blood was collected, and liver and spleen samples were isolated and weighted. The blood samples were used for measurement of white blood cell markers, and the spleen samples were used for analysis of phagocytosis, natural killer (NK) cell activity and cell proliferation using flow cytometry. The results indicated that chitosan did not markedly affect the body, liver and spleen weights at either dose. Chitosan increased the percentages of CD3 (T-cell marker), CD19 (B-cell marker), CD11b (monocytes) and Mac-3 (macrophages) when compared with the control group. However, chitosan did not affect the phagocytic activity of macrophages in peripheral blood mononuclear cells, although it decreased it in the peritoneal cavity. Treatment with 20 mg/kg chitosan led to a reduction in the cytotoxic activity of NK cells at an effector to target ratio of 25:1. Chitosan did not significantly promote B-cell proliferation in lipopolysaccharide-pretreated cells, but significantly decreased T-cell proliferation in concanavalin A-pretreated cells, and decreased the activity of GOT and GPT compared with that in the acetic acid-treated group,. In addition, it significantly increased LDH activity, to a level similar to that in normal mice, indicating that chitosan can protect against liver injury.

Osteosarcoma is the most common malignant primary bone tumor in children and young adults and lung metastasis is the main cause of death in those patients. Deguelin, a naturally occurring rotenoid, is known to be an Akt inhibitor and to exhibit cytotoxic effects, including antiproliferative and anticarcinogenic activities, in several cancers. In the present study, we determined if deguelin would inhibit migration and invasion in U-2 OS human osteosarcoma cells. Deguelin significantly inhibited migration and invasion of U-2 OS human osteosarcoma cells which was associated with a reduction of activities of matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9). Furthermore, results from western blotting indicated that deguelin decreased the cell proliferation and cell growth-associated protein levels, such as SOS1, PKC, Ras, PI3K, p-AKT(Ser473), IRE-1α, MEKK3, iNOS, COX2, p-ERK1/2, p-JNK1/2, p-p38, the cell motility and focal adhesion-associated protein levels, such as Rho A, FAK, ROCK-1, the invasion-associated protein levels, such as TIMP1, uPA, MMP-2. MMP-9, MMP-13, MMP-1 and VEGF in U-2 OS cells. Confocal microscopy revealed that deguelin reduced NF-κB p65, Rho A and ROCK-1 protein levels in cytosol. MMP-7, MMP-9 and Rho A mRNA levels were suppressed by deguelin. These in vitro results provide evidence that deguelin may have potential as a novel anti-cancer agent for the treatment of osteosarcoma and provides the rationale for in vivo studies in animal models.

Capsaicin was reported to inhibit cancer cell growth. The aim of this study was to evaluate the antitumor potential of capsaicin by studying antitumor activity in vitro as well as in vivo. The in vitro studies are to examine the effects of capsaicin on human colon cancer colo 205 cells after exposure to capsaicin. The results showed that capsaicin induced cytotoxic effects in a time- and dose-dependent manner and increased reactive oxygen species (ROS) and Ca(2+) but decreased the level of mitochondrial membrane potential (ΔΨ(m)) in colo 205 cells. Data from Western blotting analysis indicated that the levels of Fas, cytochrome c, and caspases were increased, leading to cell apoptosis. Capsaicin decreased the levels of anti-apoptotic proteins such as Bcl-2 and increased the levels of pro-apoptotic proteins such as Bax. Capsaicin-induced apoptosis in colo 205 cells was also done through the activations of caspase-8, -9 and -3. In vivo studies in immunodeficient nu/nu mice bearing colo 205 tumor xenografts showed that capsaicin effectively inhibited tumor growth. The potent in vitro and in vivo antitumor activities of capsaicin suggest that capsaicin might be developed for the treatment of human colon cancer.