Phase separation of ternary epoxy/PEI blends with higher molecular weight of tertiary component polysiloxane.

A tertiary component with higher molecular weight of epoxy terminated polysiloxane (DMS-E11) was incorporated into the diglycidyl ether of bisphenol-A (DGEBA)/thermoplastic polyetherimide (PEI) blends. In this ternary DGEBA/PEI/DMS-E11 system, 25 or 30 wt% PEI and no more than 20 wt% DMS-E11 were used to ensure the formation of a continuous PEI-rich phase via reaction induced phase separation for optimum mechanical properties of blends. The results of morphology monitoring by OM and TRLS indicated that the addition of DMS-E11 could accelerate phase separation of DGEBA/PEI. Obvious differences were observed by SEM/EDS in the final morphologies of the blends. DMS-E11 localized in the PEI-rich phase continuously while it separated with DGEBA into spherical particles in the DGEBA-rich phase. DMA measurements found that the storage modulus and T g decreased with DMS-E11 content but were compensated partly by the presence of PEI. The results of tensile tests confirmed the synergistic strengthening for epoxy resin from PEI and DMS-E11.

Two telomerase-targeting Pt(ii) complexes of jatrorrhizine and berberine derivatives induce apoptosis in human bladder tumor cells.

Two novel Pt(ii) complexes, [Pt(B-TFA)Cl]Cl (Pt1) and [Pt(J-TFA)Cl]Cl (Pt2) with jatrorrhizine and berberine derivatives (B-TFA and J-TFA) were first prepared as desirable luminescent agents for cellular applications and potent telomerase inhibitors, which can induce bladder T-24 tumor cell apoptosis by targeting telomerase, together with induction of mitochondrial dysfunction, telomere DNA damage and cell-cycle arrest. Importantly, T-24 tumor inhibition rate (TIR) was 50.4% for Pt2, which was higher than that of Pt1 (26.4%) and cisplatin (37.1%). Taken together, all the results indicated that jatrorrhizine and berberine derivatives Pt1 and Pt2 show low toxicity and could be novel Pt-based anti-cancer drug candidates.

High in vitro and in vivo antitumor activities of luminecent platinum(II) complexes with jatrorrhizine derivatives.

Two highly active anticancer Pt(II) complexes, [Pt(Jat1)Cl]Cl (Pt1) and [Pt(Jat2)Cl]Cl (Pt2), containing jatrorrhizine derivative ligands (Jat1 and Jat2) are described. Cell intake study showed high accumulation in cell nuclear fraction. Pt1 and Pt2 exhibited high selectivity for HeLa cancer cells (IC50 = 15.01 ±â€¯1.05 nM and 1.00 ±â€¯0.17 nM) comparing with HL-7702 normal cells (IC50 > 150 µM), by targeting p53 and telomerase. Pt2 containing Jat2 ligand was more potent and showed high selectivity for telomerase. It also caused mitochondria and DNA damage, sub-G1 phase arrest, and a high rate of cell apoptosis at the low dose of 1.00 nM. The HeLa tumor inhibition rate (TIR) of Pt2 was 48.8%, which was even higher than cisplatin (35.2%). In addition, Pt2 displayed green luminescent property and potent telomerase inhibition. Our findings demonstrated the promising development of platinum(II) complexes containing jatrorrhizine derivatives as novel Pt-based anti-cancer agents.

In vitro and in vivo antitumor activities of three novel binuclear platinum(II) complexes with 4'-substituted-2,2':6',2″-terpyridine ligands.

Herein, we report the design and synthesis of three novel binuclear platinum(II) complexes, [Pt(tpbtpy)Cl][Pt(DMSO)Cl3] (tpbtpy-Pt), [Pt(dthbtpy)Cl][Pt(DMSO)Cl3]⋅CH3OH (dthbtpy-Pt), and [Pt(qlbtpy)Cl][Pt(DMSO)Cl3]⋅CH3OH (qlbtpy-Pt) with 4'-(3-thiophenecarboxaldehyde)-2,2':6',2″-terpyridine (tpbtpy), 4'-(3,5-bis (1,1-dimethylethyl)-2-hydroxy-benzaldehyde)-2,2':6',2″-terpyridine (dthbtpy) and 4'-(2-quinolinecarboxaldehyde)-2,2':6',2″-terpyridine (qlbtpy) as ligands, respectively. All three novel binuclear platinum(II) complexes tpbtpy-Pt, dthbtpy-Pt, and qlbtpy-Pt were characterized by single-crystal X-ray diffraction analysis, spectroscopic analysis (ESI-MS, IR, 1H NMR), and elemental analysis. Additionally, the cytotoxicity of tpbtpy-Pt, dthbtpy-Pt and qlbtpy-Pt was assessed with human non-small cell lung cancer cell line (NCIH460 cells), yielding IC50 values in the range of 0.35-12.09 µM with tpbtpy-Pt as the most potent and qlbtpy-Pt as the least potent complexes. Mechanistic studies indicated that tpbtpy-Pt and dthbtpy-Pt induced apoptosis through mitochondrial dysfunction and telomerase inhibition. In a NCIH460 xenograft model, when administered at 10.0 mg kg-1 every 2 days, tpbtpy-Pt was shown to significantly reduce tumor growth (tumor growth inhibition rate (IR) = 70.1%, p < 0.05). Therefore, tpbtpy-Pt is a promising Pt(II) complex for further translational studies and clinical evaluation as an antitumor agent.

Synthesis of two platinum(II) complexes with 2-methyl-8-quinolinol derivatives as ligands and study of their antitumor activities.

Two platinum(II) complexes, [Pt(ClQ)(DMSO)Cl] (ClQ-Pt) and [Pt(BrQ)(DMSO)Cl] (BrQ-Pt), with 5,7-dichloro-2-methyl-8-quinolinol (H-ClQ) and 5,7-dibromo-2-methyl-8-quinolinol (H-BrQ) as ligands, respectively, have been synthesized and characterized. The single-crystal X-ray diffraction characterization as well as other spectroscopic and analytical studies of ClQ-Pt and BrQ-Pt revealed that the coordination geometry of Pt(II) can be described as a four-coordinated square planar geometry. By MTT assay, ClQ-Pt displayed the most potent activity, with IC50 values of 5.02-34.38 µM against MGC80-3, T-24, Hep-G2 and BEL-7402 tumor cells. Among them, the T-24 cells the highest sensitivity to ClQ-Pt and BrQ-Pt with IC50 value of 5.02 ±â€¯0.62 µM and 18.02 ±â€¯1.05 µM, respectively. In addition, ClQ-Pt caused a higher percentage of apoptotic T-24 cells (ca. 33.75%) than that of BrQ-Pt (ca. 23.85%) and cisplatin (ca. 12.82%). Mechanistic studies revealed that ClQ-Pt and BrQ-Pt caused T-24 cell cycle arrest at the S phase, as shown by the down-regulation of cyclin A and CDK2 expression levels. In addition, ClQ-Pt and BrQ-Pt also caused mitochondrial dysfunction. Interestingly, the in vitro anticancer activity of ClQ-Pt was higher than those of BrQ-Pt and cisplatin, more selective for T-24 tumor cells than for normal HL-7702 cells. Taken together, we concluded that the 5- and 7-substitution groups of the ClQ ligands play an important role in determining the anti-proliferation activity of the corresponding Pt(II) complexes.

Platinum(ii) complexes with rutaecarpine and tryptanthrin derivatives induce apoptosis by inhibiting telomerase activity and disrupting mitochondrial function.

Four new platinum(ii) complexes, [Pt(Rut)(DMSO)Cl2] (Rut-Pt), [Pt(Try)(DMSO)Cl2] (Try-Pt), [Pt(ITry)(DMSO)Cl2] (ITry-Pt) and [Pt(BrTry)(DMSO)Cl2] (BrTry-Pt), with rutaecarpine (Rut), tryptanthrin (Try), 8-iodine-tryptanthrin (ITry) and 8-bromo-tryptanthrin (BrTry) as ligands were synthesized and fully characterized. In these complexes, the platinum(ii) adopts a four-coordinated square planar geometry. The inhibitory activity evaluated by the MTT assay showed that BrTry-Pt (IC50 = of 0.21 ± 0.25 µM) could inhibit the growth of T-24 tumor cells (human bladder cancer cell line) more so than the other three complexes. In addition, all of these Pt complexes exhibited low toxicity against non-cancerous HL-7702 cells. BrTry-Pt induced cell cycle arrest in the S phase, leading to the down-regulation of cyclin A and CDK2 proteins. BrTry-Pt acts as a telomerase inhibitor targeting the c-myc promoter. In addition, BrTry-Pt also caused mitochondrial dysfunction. Importantly, the in vitro anticancer activity of BrTry-Pt was higher than those of Rut-Pt, Try-Pt and ITry-Pt, and it was more selective for T-24 cells than for non-cancerous HL-7702 cells.

Novel tacrine platinum(II) complexes display high anticancer activity via inhibition of telomerase activity, dysfunction of mitochondria, and activation of the p53 signaling pathway.

In this work, we designed and synthesized tacrine platinum(II) complexes [PtClL(DMSO)]⋅CH3OH (Pt1), [PtClL(DMP)] (Pt2), [PtClL(DPPTH)] (Pt3), [PtClL(PTH)] (Pt4), [PtClL(PIPTH)] (Pt5), [PtClL(PM)] (Pt6) and [PtClL(en)] (Pt7) with 4,4'-dimethyl-2,2'-bipyridine (DMP), 4,7-diphenyl-1,10-phenanthroline (DPPTH), 1,10-phenanthroline (PTH), 2-(1-pyrenecarboxaldehyde) imidazo [4,5-f]-[1,10] phenanthroline (PIPTH), 2-picolylamine (PM) and 1,2-ethylenediamine (en) as telomerase inhibitors and p53 activators. Biological evaluations demonstrated that Pt1Pt7 exhibited cytotoxic activity against the tested NCIH460, Hep-G2, SK-OV-3, SK-OV-3/DDP and MGC80-3 cancer cell lines, with Pt5 displaying the highest cytotoxicity. Pt5 exhibited an IC50 value of 0.13 ±â€¯0.16 µM against SK-OV-3/DDP cancer cells and significantly reduced tumor growth in a Hep-G2 xenograft mouse model (tumor growth inhibition (TGI) = 40.8%, p < 0.05) at a dose of 15.0 mg/kg. Interestingly, Pt1Pt7 displayed low cytotoxicity against normal HL-7702 cells. Mechanistic studies revealed that these compounds caused cell cycle arrest at the G2/M and S phases, and regulated the expression of CDK2, cyclin A, p21, p53 and p27. Further mechanistic studies showed that Pt5 induced SK-OV3/DDP cell apoptosis via dysfunction of mitochondria, inhibition of the telomerase activity by directly targeting the c-myc promoter, and activation of the p53 signaling pathway. Taken together, Pt5 has the potential to be further developed as a new antitumor drug.

Synthesis, characterization and biological evaluation of six highly cytotoxic ruthenium(ii) complexes with 4'-substituted-2,2':6',2''-terpyridine.

Herein, six ruthenium(ii) terpyridine complexes, i.e. [RuCl2(4-EtN-Phtpy)(DMSO)] (Ru1), [RuCl2(4-MeO-Phtpy)(DMSO)] (Ru2), [RuCl2(2-MeO-Phtpy)(DMSO)] (Ru3), [RuCl2(3-MeO-Phtpy)(DMSO)] (Ru4), [RuCl2(1-Bip-Phtpy)(DMSO)] (Ru5), and [RuCl2(1-Pyr-Phtpy)(DMSO)] (Ru6) with 4'-(4-diethylaminophenyl)-2,2':6',2''-terpyridine (4-EtN-Phtpy), 4'-(4-methoxyphenyl)-2,2':6',2''-terpyridine (4-MeO-Phtpy), 4'-(2-methoxyphenyl)-2,2':6',2''-terpyridine (2-MeO-Phtpy), 4'-(3-methoxyphenyl)-2,2':6',2''-terpyridine (3-MeO-Phtpy), 4'-(1-biphenylene)-2,2':6',2''-terpyridine (1-Bip-Phtpy), and 4'-(1-pyrene)-2,2':6',2''-terpyridine (1-Pyr-Phtpy), respectively, were synthesized and fully characterized. The MTT assay demonstrates that the in vitro anticancer activity of Ru1 is higher than that of Ru2-Ru6 and more selective for Hep-G2 cells than for normal HL-7702 cells. In addition, various biological assays show that Ru1 and Ru6, especially the Ru1 complex, are telomerase inhibitors targeting c-myc G4 DNA and also cause apoptosis of Hep-G2 cells. With the same Ru center, the in vitro antitumor activity and cellular uptake ability of the 4-EtN-Phtpy and 1-Bip-Phtpy ligands follow the order 4-EtN-Phtpy > 1-Bip-Phtpy.

Synthesis and antitumor mechanisms of two novel platinum(ii) complexes with 3-(2'-benzimidazolyl)-7-methoxycoumarin.

Two novel platinum(ii) complexes, [PtCl2(H-MeOBC)(DMSO)] (Pt1) and [Pt2Cl3(MeOBC)(DMSO)2] (Pt2), with 3-(2'-benzimidazolyl)-8-methoxycoumarin (H-MeOBC) as the ligand were synthesized and evaluated for their antiproliferative activity. Among all the tumor cells, dual-Pt(ii) complex Pt2 exhibited the most potent activity, with an IC50 value of 0.5 ± 0.2 µM against cisplatin-resistant SK-OV-3/DDP cancer cells. In the case of SK-OV-3/DDP cells, Pt2 displayed a 20.1-196.0-fold increased activity when compared with cisplatin, H-MeOBC and Pt1. Importantly, Pt1 and Pt2 displayed low inhibitory rates against normal HL-7702 cells. Further investigation revealed that Pt2 is a novel telomerase inhibitor binding to c-myc promoter elements. Mechanistic studies demonstrated that dual-Pt(ii) complex Pt2 arrests the cell cycle at the G2/M phase and induces apoptosis and causes mitochondrial dysfunction.

Synthesis, Characterization, and Cytotoxicity of the Cobalt (III) Complex with N,N-Diethyl-4-(2,2':6',2''-terpyridin-4'-yl)aniline.

A cobalt(III) complex, [Co(L)2 ](ClO4 )3 (1), in which the ligand L was N,N-diethyl-4-(2,2':6',2''-terpyridin-4'-yl)aniline (L), was synthesized and fully characterized. This new cobalt(III) complex 1 exhibited selective cytotoxicity against HeLa, T-24, A549, MGC80-3, HepG2, and SK-OV-3 cells with IC50 values in the micromolar range (0.52 - 4.33 µm), and it exhibited low cytotoxicity against normal HL-7702 cells. The complex 1 was the most potent against the T-24 cells. It was found that 1 could cause the cell cycle arrest in G1 phase, and it exerted its antitumor activity mainly via disruption of mitochondrial function.

Overexpression of miR-34c inhibits high glucose-induced apoptosis in podocytes by targeting Notch signaling pathways.

Recent findings have shown that microRNAs play critical roles in the pathogenesis of diabetic nephropathy. miR-34c has been found to inhibit fibrosis and the epithelial-mesenchymal transition of kidney cells. However, the role of miR-34c in diabetic nephropathy has not been well studied. The current study was designed to investigate the role and potential underlying mechanism of miR-34c in regulating diabetic nephropathy. After treating podocytes with high glucose (HG) in vitro, we found that miR-34c was downregulated and that overexpression of miR-34c inhibited HG-induced podocyte apoptosis. The direct interaction between miR-34c and the 3'-untranslated region (UTR) of Notch1 and Jagged1 was validated by dual-luciferase reporter assay. Moreover, Notch1 and Jagged1 as putative targets of miR-34c were downregulated by miR-34c overexpression in HG-treated podocytes. Overexpression of miR-34c inhibited HG-induced Notch signaling pathway activation, as indicated by decreased expression of the Notch intracellular domain (NICD) and downstream genes including Hes1 and Hey1. Furthermore, miR-34c overexpression increased the expression of the anti-apoptotic gene Bcl-2, and decreased the expression of the pro-apoptotic protein Bax and cleaved Caspase-3. Additionally, the phosphorylation of p53 was also downregulated by miR-34c overexpression. Taken together, our findings suggest that miR-34c overexpression inhibits the Notch signaling pathway by targeting Notch1 and Jaggged1 in HG-treated podocytes, representing a novel and potential therapeutic target for the treatment of diabetic nephropathy.

Herpes simplex virus-1 infection or Simian virus 40-mediated immortalization of corneal cells causes permanent translocation of NLRP3 to the nuclei.

AIM: To investigate into the potential involvement of pyrin containing 3 gene (NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of corneas against viruses. METHODS: The herpes viral keratitis model was utilized in BALB/c mice with inoculation of herpes simplex virus-1 (HSV-1). Corneal tissues removed during therapy of patients with viral keratitis as well as a Simian vacuolating virus 40 (SV40)-immortalized human corneal epithelial cell line were also examined. Immunohistochemistry was used to detect NLRP3 in these subjects, focusing on their distribution in tissue or cells. Western blot was used to measure the level of NLRP3 and another two related molecules in NLPR3 inflammasome, namely caspase-1 and IL-1ß. RESULTS: The NLRP3 activation induced by HSV-1 infection in corneas was accompanied with redistribution of NLRP3 from the cytoplasm to the nucleus in both murine and human corneal epithelial cells. Furthermore, in the SV40-immortalized human corneal epithelial cells, NLRP3 was exclusively located in the nucleus, and treatment of the cells with high concentration of extracellular potassium (known as an inhibitor of NLRP3 activation) effectively drove NLRP3 back to the cytoplasm as reflected by both immunohistochemistry and Western blot. CONCLUSION: It is proposed that herpes virus infection activates and causes redistribution of NLRP3 to nuclei. Whether this NLRP3 translocation occurs with other viral infections and in other cell types merit further study.

In-situ X-ray diffraction snapshotting: determination of the kinetics of a photodimerization within a single crystal.

In a single-crystal-to-single-crystal (SCSC) transformation, a preformed three-dimensional coordination polymer,[Ni3(oba)2(bpe)2(SO4)(H2O)4]· H2O (H2oba = 4,4'-oxydibenzoic acid; bpe = (E)-1,2-di(pyridin-4-yl)ethane) (1), was shown to undergo a [2+2] cycloaddition reaction upon exposure to UV irradiation. The kinetics of this reaction were followed by taking "snapshots" of the solid state transformation using in situ single crystal X-ray crystallography; a first order process was indicated. The reaction rate was influenced by many factors such as the separation of the sample from the UV light source, the heat produced by the UV irradiation, the light flux of the UV lamp used, the size of the single-crystal and the powder samples. The investigation of the kinetics was complemented by (1)H NMR studies. The results clearly demonstrate that in situ single-crystal X-ray diffraction is able to provide useful insights into the gradual formation of the photoproducts and the reaction processes. The work also offers a clear indication that it is possible to use the technique to study the kinetics of other photocycloaddition reactions and SCSC processes in general.

[Investigation of sexual function in male kidney transplant recipients].

OBJECTIVE: To observe the change of sexual function in male kidney transplant recipients. METHODS: Sixty married males, aged 26 to 45 years, who had received kidney transplantations at least half a year before and whose serum creatinine (Scr) was under 200 mumol/L, were selected randomly in the study. Sexual functions were reviewed before and after the patients' renal failure and after kidney transplantations. The results were analyzed in Chi-Square test methods. RESULTS: Their sexual functions, significantly aggravated after renal failure, were improved after kidney transplantations, but failed to return to normal. The recipients had a common worry that their sex lives might affect the renal grafts. CONCLUSIONS: Kidney transplantations significantly improve the sexual functions of these renal failure patients. It is quite necessary to provide sexological guidance to kidney transplant recipients and their spouses.