Changes of T-lymphocyte subpopulation and differential expression pattern of the T-bet and GATA-3 genes in diffuse large B-cell lymphoma patients after chemotherapy

BACKGROUND AND OBJECTIVE: T cell-mediated immunity plays an important role in enhancing antitumor response.This study aimed to investigate the changes in the T-lymphocyte subpopulation and to characterize the differential expression pattern of corresponding regulatory genes in peripheral blood mononuclear cells (PBMCs) from diffuse large B cell lymphoma (DLBCL) patients before and after chemotherapy. METHODS: A total of 56 DLBCL patients were recruited for analysis of T-cell subset distribution in the peripheral blood using flow cytometry; serum interferon (IFN)-γ and interleukin (IL)-4 levels using enzyme-linked immunosorbent assays; and early growth response protein 1 (EGR-1), T-bet, GATA-binding protein 3 (GATA-3), and transforming growth factor (TGF)-β mRNA levels using quantitative reverse-transcription polymerase chain reaction. Twenty-six healthy subjects served as controls. RESULTS: The percentage of CD3(+)CD4(+)T lymphocytes in peripheral blood from DLBCL patients was significantly decreased, whereas the percentages of CD3(+)CD8(+)T and CD4(+)CD25(+)T cells were significantly increased compared to those in controls (p < 0.05). Serum levels of IFN-γ and IL-4 were also significantly lower in DLBCL patients than those in controls (p < 0.05), and the levels of EGR-1, T-bet, and GATA-3 mRNA in PBMCs were lower (2.69 ± 1.48, 9.43 ± 2.14, and 20.83 ± 9.05 fold, respectively) in DLBCL patients than those in controls. Furthermore, there was a positive association between the levels of EGR-1 and T-bet mRNA (p = 0.001). However, the level of TGF-β mRNA was significantly increased in DLBCL patients, which was inversely associated with the T-bet mRNA level (p = 0.008), but positively associated with the percentage of T regulatory cells in PBMCs (p = 0.011). After three cycles of chemotherapy, the distribution of T-lymphocyte subsets in DLBCL patients were changed, and the levels of EGR-1, T-bet, and GATA-3 mRNA were significantly increased (p < 0.05) compared to those before chemotherapy. CONCLUSIONS: These results demonstrate the changes in T-lymphocyte subpopulations and the altered expression 34 pattern of the corresponding regulatory genes in PBMCs from DLBCL patients after chemotherapy, which are associated with the response of patients to treatment. The preferential expression of the T-bet gene after chemotherapy was closely correlated with the increased expression of the EGR-1 gene and decreased expression of the TGF-β gene

Metal-containing functional polymers: (I) Room temperature magnetic materials and (II) Anion exchange membranes

Nanostructured magnetic materials are important for various applications, and hence their development is critical for the advancement of science and technology. Coupling self-assembly to the generation of magnetic materials in a simple, straight-forward manner has remained a challenge. Here, a series of novel cobalt-functionalized block copolymers (BCPs) with various block ratios were synthesized using ring-opening metathesis polymerization (ROMP). These BCPs self-assembled into different nanostructured morphologies, including cylindrical, lamellar, and inverted cylindrical phases. Upon a simple heat treatment, all these nanostructured materials exhibited room temperature ferromagnetic (RTF) behavior due to the nanoconfinement of the cobalt species within one phase. The effect of dimensionality, or the degree of nanoconfinement, on the macroscopic magnetic properties was studied using superconducting quantum interference device (SQUID) magnetometer. The most highly constrained cylindrical morphology yielded the highest coercivity. The inverted cylindrical morphology, analogous to antidot materials, in which a 3D magnetic matrix is confined between diamagnetic cylinders, showed the second highest coercivity, while the least confined lamellar morphology exhibited the lowest coercivity value. A series of metal-containing block-random copolymers composed of an alkyl-functionalized homo block (C16) and a random block of cobalt complex- (Co) and ferrocene-functionalized (Fe) units was synthesized via ROMP. Taking advantage of the block-random architecture, the influence of dipolar interactions on the magnetic properties of these nanostructured BCPs was studied by varying the molar ratio of the Co units to the Fe units, while maintaining the cylindrical phase-separated morphology. DC magnetic measurements, including magnetization versus field, zero-field-cooled and field cooled, as well as AC susceptibility measurements, showed that the magnetic properties of the nanostructured BCPs could be easily tuned by diluting the cobalt density with Fe units in the cylindrical domains. Decreasing the cobalt density weakened the dipolar interactions of the cobalt nanoparticles, leading to the transition from a room temperature ferromagnetic to a superparamagnetic material. These results confirmed that dipolar interactions of the cobalt nanoparticles within the phase-separated domains were responsible for the RTF properties of the nanostructured BCPs. The effect of domain size on the magnetic properties of these RTF materials was investigated using a series of five cobalt-containing BCPs with various molecular weights and constant block ratios. The BCPs self-assembled into cylindrical morphologies with different domain sizes upon solvent annealing, and then were converted to RTF materials upon a simple heat treatment. The domain sizes of these RTF materials did not show a significant impact on their coercivity values, possibly because the domain size range investigated was not large enough and the cobalt-cobalt dipolar interactions were nearly constant throughout. At the same time, this study confirms that the RTF materials generated from these novel BCPs are robust. (Abstract shortened by UMI.

Metallo-Supramolecular Cyclic Polymers

Cyclic brush polymers represent an exciting new macromolecular topology. For the first time, this new topology has been combined with metallo-supramolecular interactions to construct novel cyclic brush polymers. Here, ring-expansion metathesis polymerization was used to synthesize a universal cyclic template with a polynorbornene backbone, which was further modified with the metal-chelating synthon terpyridine. The terpyridine side chains served as the key supramolecular unit for the creation of cyclic polymer brushes and gels. This metallo-supramolecular functionality allowed direct visualization of the cyclic brush polymers by transmission electron microscopy for the first time. This demonstration should open a new area in which supramolecular interactions are used to build an array of novel cyclic brush copolymers as well as other cyclic-polymer-based architectures generating new materials

Metal-Cation-Based Anion Exchange Membranes

Here we present the first metal-cation-based anion exchange membranes (AEMs), which were synthesized by copolymerization and cross-linking of a norbornene monomer functionalized with a water-soluble bis­(terpyridine)­ruthenium­(II) complex and dicyclopentadiene. Each ruthenium complex has two associated counteranions, unlike most ammonium- and phosphonium-based membranes with single cation–anion pairs. The resulting AEMs show anion conductivities and mechanical properties comparable to those of traditional quaternary-ammonium-based AEMs as well as good alkaline stability and methanol tolerance. These results suggest that metal-cation-based polymers hold promise as a new class of materials for anion-conducting applications

Nanostructured Block-Random Copolymers with Tunable Magnetic Properties

It was recently shown that block copolymers (BCPs) produced room-temperature ferromagnetic materials (RTFMs) due to their nanoscopic ordering and the cylindrical phase yielded the highest coercivity. Here, a series of metal-containing block-random copolymers composed of an alkyl-functionalized homo block (C₁₆) and a random block of cobalt complex- (Co) and ferrocene-functionalized (Fe) units was synthesized via ring-opening metathesis polymerization. Taking advantage of the block-random architecture, the influence of dipolar interactions on the magnetic properties of these nanostructured BCP materials was studied by varying the molar ratio of the Co units to the Fe units, while maintaining the cylindrical phase-separated morphology. DC magnetic measurements, including magnetization versus field, zero-field-cooled, and field-cooled, as well as AC susceptibility measurements showed that the magnetic properties of the nanostructured BCP materials could be easily tuned by diluting the cobalt density with Fe units in the cylindrical domains. Decreasing the cobalt density weakened the dipolar interactions of the cobalt nanoparticles, leading to the transition from a room temperature ferromagnetic (RTF) to a superparamagnetic material. These results confirmed that dipolar interactions of the cobalt nanoparticles within the phase-separated domains were responsible for the RTF properties of the nanostructured BCP materials

Water Uptake and Ion Mobility in Cross-Linked Bis(terpyridine)ruthenium-Based Anion Exchange Membranes

As an alternative to benzyltrimethylammonium (BTMA)-functionalized polymers for use as anion exchange membranes (AEMs), we report here on the properties of cross-linked polymers containing tethered bis­(terpyridine)­ruthenium­(II) complexes as AEMs with chloride, bicarbonate, and hydroxide mobile ions. The maximum conductivity for the Ru­(II)-complex-based membranes, measured at 30 °C in liquid water, depended on the water uptake and degree of cross-linking more than on the ion exchange capacity (IEC). For membranes with 2:1 cross-linker:monomer ratio, the highest conductivities were 7.9 mS cm^–1 for the 1.6 mequiv g^–1 IEC membrane in chloride form, with a hydration number of 51, and 6.5 mS cm^–1 for the 1.8 mequiv g^–1 IEC membrane in bicarbonate form, with a hydration number of 124. Additionally, we calculated the chloride and bicarbonate ion diffusion coefficients from conductivity measurements and the samples’ hydrated ion concentration, which enabled the membrane ion diffusion coefficients (<i>D</i>) to be related to the dilute solution ion diffusivity (<i>D</i>₀) through the ratio <i>D</i>/<i>D</i>₀. Although membranes with a 1:1 cross-linker:monomer ratio had the lowest barrier to transport, indicated by their high <i>D</i>/<i>D</i>₀ ratio, membranes with a 2:1 cross-linker:monomer ratio demonstrated the highest conductivity due to their balanced water uptake and ion concentration in the hydrated state. At hydration numbers greater than 20, the diffusion coefficient of the mobile chloride or bicarbonate ions was within an order of magnitude of the dilute solution limit. Finally, the properties of the Ru­(II)-complex-based AEMs were compared to BTMA-based AEMs by considering the size and charge distribution of the cationic center