Different Role of Tumor Necrosis Factor-α Polymorphism in Non-Hodgkin Lymphomas among Caucasian and Asian Populations: A Meta-Analysis

Tumor necrosis factor-α (TNF-α) is an immunoregulatory cytokine involved in B- and T-cell function, and also plays an important role in inflammation and cancer. TNF-α-308G>A has been associated with constitutively elevated TNF-α expression. Several studies have reported the association between the TNF-α-308G>A polymorphism and non-Hodgkin lymphomas (NHL) risk, however, results are still inconsistent. To solve these conflicts, we conducted the first meta-analysis to assess the effect of TNF-α-308G>A polymorphism on the risk of NHL and various subtypes (additive model) including 10,619 cases and 12,977 controls in Caucasian and Asian populations. Our meta-analysis indicated that TNF-α-308G>A polymorphism is not associated with NHL risk when pooling all studies together (OR = 1.06, 95% CI: 0.92–1.23, p = 0.413). In stratified analyses, we found TNF-α-308A allele was significantly associated with higher risk of NHL, B-cell lymphomas (BCL), T-cell lymphomas (TCL) and diffuse large B-cell lymphomas (DLBCL) in Caucasians (OR = 1.22, 95% CI: 1.06–1.40, p = 0.007; OR = 1.18, 95% CI: 1.03–1.34, p = 0.014; OR = 1.20, 95% CI: 1.01–1.42, p = 0.040; OR = 1.21, 95% CI: 1.11–1.32, p < 0.001, respectively). Interestingly, it was associated with decreased risk of NHL, BCL and DLBCL in Asians (OR = 0.75, 95% CI: 0.66–0.86, p < 0.001; OR = 0.70, 95% CI: 0.52–0.94, p = 0.018; OR = 0.70, 95% CI: 0.57–0.86, p = 0.001). These findings also suggest TNF-α might play a distinct role in pathogenesis of NHL in different populations.     

Tetramethylpyrazine Protects Retinal Capillary Endothelial Cells (TR-iBRB2) against IL-1β-Induced Nitrative/Oxidative Stress

Blood-retinal barrier (BRB) breakdown is one of the primary causes of diabetic retinopathy (DR). The pro-inflammatory factor interleukin-1β (IL-1β) was reported to be involved in the induction of BRB breakdown during the pathogenesis of DR. In the present study, we investigated the protective effect of tetramethylpyrazine (TMP), a major active component of the traditional herb Ligusticum chuanxiong, on IL-1β-induced cell death of the rat retinal capillary endothelial TR-iBRB2 cells. Our results showed that IL-1β-induced cell dysfunction in TR-iBRB2 cells via inducing nitrative/oxidative stress; however, such effect was attenuated with the pre-treatment of TMP. The cellular protective effect of TMP was likely to be mediated through the inhibition of inducible nitric oxide synthase (iNOS) expression and leukostasis as well as suppression of reactive oxygen species (ROS) generation, mitochondrial dysfunction and MAPKs activation. These findings significantly contribute to a better understanding of the protective effect of TMP in DR and form the basis of the therapeutic development of TMP in treating such disease in the future.     

<Emphasis Type="Italic">Trans</Emphasis> Fatty Acids Suppress TNF-α-Induced Inflammatory Gene Expression in Endothelial (HUVEC) and Hepatocellular Carcinoma (HepG2) Cells

Trans fatty acids (TFA) intake has been linked to cardiovascular diseases and liver diseases; yet the effect of TFA on inflammation remains controversial. Accordingly, the objective of this paper was to determine the in vitro effects of TFA on inflammatory gene expression. Human umbilical vein endothelial cells (HUVEC) and human hepatocellular carcinoma (HepG2) cells were treated for 24 h with either trans-vaccenic acid (tVA), trans-palmitoleic acid (tPA) or elaidic acid (EA) at concentrations of 5–150 µM, or with a mixture of tVA and tPA (150/50 µM). All TFA were highly incorporated into cell membranes, as determined by gas chromatography, representing 15–20% of total fatty acids in HUVEC and 3–8% in HepG2 cells. Incorporation of EA, a common industrial TFA, increased the ratio of the stearoyl-CoA desaturase (SCD-1), a key enzyme involved in fatty acid metabolism. Ruminant TFA, including tVA, tPA and the mixture of tVA and tPA, significantly reduced the TNF-α-induced gene expression of TNF, VCAM-1 and SOD2 in HUVEC, as well as TNF and IL-8 in HepG2 cells. EA also decreased inflammatory gene expression in HUVEC, but not in HepG2 cells. The inhibition of peroxisome proliferator-activated receptor (PPAR)-γ did not influence the effects of TFA on gene expression. Overall, physiological and supraphysiological concentrations of TFA, especially tVA and tPA, prevented inflammatory gene expression in vitro. This effect is independent of PPAR-γ activation and may be due to an alteration of fatty acid metabolism in cell membranes caused by the high incorporation of TFA.     

The -308G/A of Tumor Necrosis Factor (TNF)-α and 825C/T of Guanidine Nucleotide Binding Protein 3 (GNB3) are Associated with the Onset of Acute Myocardial Infarction and Obesity in Taiwan

Acute myocardial infarction is a highly prevalent cardiovascular disease in Taiwan. Among several etiological risk factors, obesity and inflammation are strongly associated with the frequency of hypertension, cardiovascular disease, diabetes, and myocardial infarction. To discriminate obesity- and inflammation-related genes and the onset of acute myocardial infarction (AMI), a case-control study was conducted to investigate the association of the -308G/A polymorphisms of tumor necrosis factor (TNF)-α and the C825T polymorphism of guanidine nucleotide binding protein 3 (GNB3) with the onset of AMI among Taiwanese cohorts. A total of 103 AMI patients and 163 matched normal control samples were enrolled in the present study. The genomic DNA was extracted and subjected into polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis. An association between the A homozygosity of the TNF-α-308G/A polymorphism and the onset of AMI was observed among the male subjects (p = 0.026; Spearman index = 0.200, p = 0.008). An association between the T homozygosity of GNB3 C825T polymorphism and obesity was also observed (Fisher's exact, p = 0.009). The TT genotype has a protective effect against acquiring AMI among the obese female population in Taiwan (Fisher's exact, p = 0.032). In conclusion, TNF-α-308G/A and the GNB3 C825T polymorphisms are associated with obesity and AMI in the Taiwanese population.     

A Lack of Evidence for an Ecological Role of the Putative Allelochemical (±)-Catechin in Spotted Knapweed Invasion Success

Allelopathy is a notoriously difficult mechanism to demonstrate. There has been a recent resurgence of interest in allelopathy because of the work done on the invasive weed spotted knapweed and its putative allelochemical, (±)-catechin. In this study we collected and analyzed soil samples taken from three, long-term knapweed infested sites in Montana, USA during the summer and fall of 2005. We only detected catechin in all the soil cores at one time point (August, 2005) at two of the sites. Field levels from these two sites were nearly three orders of magnitude lower than what has previously been reported to cause reduced growth in a sensitive native species. Fourteen percent of the remaining soil cores contained low but detectable levels (<0.11 ppm) of (±)-catechin. Additional experiments indicated that soil moisture appears to play a significant role in whether or not catechin degrades rapidly or remains in the soil. Adding to previous work, this paper sheds doubt on the importance of this chemical in spotted knapweed invasion success.     

Behavior of (–)-α-Bisabolol and (–)-α-Bisabololoxides A and B in Camomile Flower Extraction with Supercritical Carbon Dioxide

Abstract

A systematic study of the extraction behavior of selected components of camomile flowers in extraction with supercritical carbon dioxide was carried out. (–)-α-Bisabolol and its A and B oxides, which have a wide importance in pharmacology and standardization of camomile flower products, were selected. The dependence of the yield of selected components on the pressure and/or temperature of supercritical extraction was investigated. The results obtained were correlated.     

Mechanism of the Formation of Ba2Ti9O20-Based Phases in the Course of Solid-Phase Interaction in the BaO–TiO2(ZrO2) and Cs2O–BaO–TiO2(ZrO2) Systems

The mechanism of solid-phase interaction in the BaO–TiO₂(ZrO₂) and Cs₂O–BaO–TiO₂(ZrO₂) systems is investigated. It is established that the formation of the Ba₂Ti₉O₂₀ compound and Ba₂Ti₉O₂₀-based solid solutions is a multistage process proceeding through the formation of intermediate phases. The solid-phase interaction in the BaO–TiO₂(ZrO₂) system occurs through the formation of the BaTi₄O₉ intermediate compound. The Ba₂Ti₉O₂₀ single-phase product is formed only in the presence of ZrO₂ (0.82 mol %) upon heat treatment at a temperature of 1250°C for 5 h. In the Cs₂O–BaO–TiO₂(ZrO₂) system, the BaTi₅O₁₁ metastable intermediate phase is formed at the first stage of the solid-phase interaction. The Cs _x Ba_{2 – x/2}Ti_{9 – y} Zr _y O₂₀ single-phase solid solutions are prepared upon heat treatment at 1100°C for 1 h. It is demonstrated that, in the Ba₂Ti₉O₂₀ structure, cesium can isomorphously substitute for barium with the formation of Cs _x Ba_{2 – x/2}Ti_{9 – y} Zr _y O₂₀ solid solutions (0 x 0.8, y = 0 and 0.09).     

Phase and melting relationships of β, α and α′-Ca3(PO4)2 polymorphs in the Ca3(PO4)2-Zn3(PO4)2 system

In order to provide an exact knowledge of the phase transitions and melting relationships of Ca₃(PO₄)₂ (TCP) in the presence of zinc, a revisited version of the rich-Ca₃(PO₄)₂ region of the phase diagram of the system Ca₃(PO₄)₂-Zn₃(PO₄)₂ has been established in the present work. Experimental determination of this diagram was carried out by solid-state reactions of samples prepared from pure NH₄H₂PO₄, CaCO₃ and ZnO raw materials. X-ray Diffraction, Differential Thermal Analyses and Field Emission Scanning Electron Microscopy studies allowed to revise the α, β, α + β-TCP phase stability fields, delimitating for the first time the biphasic α + α′-TCP field and the melting relationships in the high temperature region of the system. The results allowed to determine two peritectic invariant points, at ≈1400 °C for 95 mol% Ca₃(PO₄)₂ and at ≈1490 °C for ≈99.5 mol% Ca₃(PO₄)₂.     

Investigation of Spectroscopic Properties and Spin-Orbit Splitting in the X(2)Π and A(2)Π Electronic States of the SO(+) Cation

The potential energy curves (PECs) of the X(2)Π and A(2)Π electronic states of the SO(+) ion are calculated using the complete active space self-consistent field method, which is followed by the internally contracted multireference configuration interaction (MRCI) approach for internuclear separations from 0.08 to 1.06 nm. The spin-orbit coupling effect on the spectroscopic parameters is included using the Breit-Pauli operator. To improve the quality of PECs and spin-orbit coupling constant (A(0)), core-valence correlation and scalar relativistic corrections are included. To obtain more reliable results, the PECs obtained by the MRCI calculations are corrected for size-extensivity errors by means of the Davidson modification (MRCI+Q). At the MRCI+Q/aug-cc-pV5Z+CV+DK level, the A(0) values of the SO(+)(X(2)Π(1/2, 3/2)) and SO(+)(A(2)Π(1/2, 3/2)) are 362.13 and 58.16 cm(-1) when the aug-cc-pCVTZ basis set is used to calculate the spin-orbit coupling splitting, and the A(0) of the SO(+)(X(2)Π(1/2, 3/2)) and SO(+)(A(2)Π(1/2, 3/2)) are 344.36 and 52.90 cm(-1) when the aug-cc-pVTZ basis set is used to calculate the spin-orbit coupling splitting. The conclusion is drawn that the core-valence correlations correction makes the A(0) slightly larger. The spectroscopic results are obtained and compared with those reported in the literature. Excellent agreement exists between the present results and the measurements. The vibrational manifolds are calculated, and those of the first 30 vibrational states are reported for the J = 0 case. Comparison with the measurements shows that the present vibrational manifolds are both reliable and accurate.     

Enhanced cGMP Interactor Rap Guanine Exchange Factor 4 (EPAC2) Expression and Activity in Degenerating Photoreceptors: A Neuroprotective Response?

The disease retinitis pigmentosa (RP) leads to photoreceptor degeneration by a yet undefined mechanism(s). In several RP mouse models (i.e., rd mice), a high cyclic GMP (cGMP) level within photoreceptors is detected, suggesting that cGMP plays a role in degeneration. The rap guanine exchange factor 4 (EPAC2) is activated by cyclic AMP (cAMP) and is an accepted cGMP-interacting protein. It is unclear whether and how cGMP interacts with EPAC2 in degenerating photoreceptors; we therefore investigated EPAC2 expression and interactions with cGMP and cAMP in retinas of the rd1 and rd10 models for retinal degeneration. EPAC2 expression in the photoreceptor layer increased significantly during rd1 and rd10 degeneration, and an increase in EPAC2 interactions with cGMP but not cAMP in the rd1 was also seen via a proximity ligation assay on histological sections. Retinal explant cultures revealed that pharmacological inhibition of the EPAC2 activity reduced the photoreceptor layer thickness in the rd10 retina, suggesting that EPAC2 inhibition promotes degeneration. Taken together, our results support the hypothesis that high degeneration-related cGMP leads to increased EPAC2 and cGMP interactions, inhibiting EPAC2. By inference, EPAC2 could have neuroprotective capacities that may be exploited in the future.     

Fraction from Wax Apple [Syzygium samarangense (Blume) Merrill and Perry] Fruit Extract Ameliorates Insulin Resistance via Modulating Insulin Signaling and Inflammation Pathway in Tumor Necrosis Factor α-Treated FL83B Mouse Hepatocytes

Inflammation is associated with the development of insulin resistance in Type 2 diabetes mellitus. In the present study, mouse FL83B cells were treated with tumor necrosis factor-alpha (TNF-α) to induce insulin resistance, and then co-incubated with a fraction from wax apple fruit extract (FWFE). This fraction significantly increased the uptake of the nonradioactive fluorescent indicator 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose (2-NBDG) in insulin resistant cells. Western blot analysis revealed that, compared with the TNF-α-treated control group, FWFE increased the expression of the insulin receptor (IR), insulin receptor substrate-1 (IRS-1), protein kinase B (Akt/PKB), phosphatidylinositol-3 kinase (PI3K), and glucose transporter 2 (GLUT-2), and increased IR tyrosyl phosporylation, in insulin resistant FL83B cells. However, FWFE decreased phosphorylation of c-Jun N-terminal kinases (JNK), but not the expression of the intercellular signal-regulated kinases (ERK), in the same cells. These results suggest that FWFE might alleviate insulin resistance in TNF-α-treated FL83B cells by activating PI3K-Akt/PKB signaling and inhibiting inflammatory response via suppression of JNK, rather than ERK, activation.     

Electronic properties and stability of M2O3 (M = Al,Ga, In) and alloy (MxGa1-x)2O3 in α and β phases: A theoretical study

Ga₂O₃ is clearly emerging as an important wide band-gap semiconductor. Band-gap engineering is now highly demanded for expanding its applications. Alloying with the same group of metal oxides is a straightforward and effective way. In this work, by using hybrid density functional theory calculations, the structural, electronic properties, and phase stability of group IIIA (Al, Ga, In) metal oxides and their ternary alloys (M_xGa_1-x)₂O₃ (M = Al, In) in the corundum and monoclinic phases are systematically investigated. The lattice constants, elastic constants, modulus, formation energies, band-gaps, band-gap deformation potentials, band-edge alignments, band-gap bowing, and ternary alloy formation energies are obtained. The basic relations between the geometric structure and electronic properties are discussed. It is found that the cation ordered structure is the most stable alloy structure in the monoclinic phase, rather than the random alloy structure as is commonly thought. A phase stability diagram of the (M_xGa_1-x)₂O₃ alloys is established, showing that the stable phase of the alloy changes from the monoclinic phase to the corundum phase when the incorporation of Al₂O₃ (In₂O₃) is greater than 69% (76%). These results can be used to understand the relative experimental data and shed some light on the synthesis and device design efforts of Ga₂O₃.     

A comparative raman study of the local structure in (Ge2S3) x (As2S3)1-x and (GeS2) x (As2S3)1−x glasses

The Raman spectra of glasses in the ternary (Ge₂S₃) _x (As₂S₃)_1−x and (GeS₂) _x (As₂S₃)_1−x systems are reported. It is shown that the degree of disorder in the (Ge₂S₃) _x (As₂S₃)_1−x glasses increases with an increase in the Ge content. The differences in the spectra of glasses with the same molar content of As₂S₃ are discussed in terms of the changes occurring in the local structure due to deviations from the stoichiometry. The observed changes in the intensity of the boson peak indicate changes in the medium-range order structure of the glasses under study.     

Modulation of the PI3K/Akt Pathway and Bcl-2 Family Proteins Involved in Chicken’s Tubular Apoptosis Induced by Nickel Chloride (NiCl2)

Exposure of people and animals to environments highly polluted with nickel (Ni) can cause pathologic effects. Ni compounds can induce apoptosis, but the mechanism and the pathway of Ni compounds-induced apoptosis are unclear. We evaluated the alterations of apoptosis, mitochondrial membrane potential (MMP), phosphoinositide-3-kinase (PI3K)/serine-threonine kinase (Akt) pathway, and Bcl-2 family proteins induced by nickel chloride (NiCl₂) in the kidneys of broiler chickens, using flow cytometry, terminal deoxynucleotidyl transferase 2ʹ-deoxyuridine 5ʹ-triphosphate dUTP nick end-labeling (TUNEL), immunohistochemstry and quantitative real-time polymerase chain reaction (qRT-PCR). We found that dietary NiCl₂ in excess of 300 mg/kg resulted in a significant increase in apoptosis, which was associated with decrease in MMP, and increase in apoptosis inducing factor (AIF) and endonuclease G (EndoG) protein and mRNA expression. Concurrently, NiCl₂ inhibited the PI3K/Akt pathway, which was characterized by decreasing PI3K, Akt1 and Akt2 mRNA expression levels. NiCl₂ also reduced the protein and mRNA expression of anti-apoptotic Bcl-2 and Bcl-xL and increased the protein and mRNA expression of pro-apoptotic Bax and Bak. These results show that NiCl₂ causes mitochondrial-mediated apoptosis by disruption of MMP and increased expression of AIF and EndoG mRNA and protein, and that the underlying mechanism of MMP loss involves the Bcl-2 family proteins modulation and PI3K/Akt pathway inhibition.     

New Efficient Synthesis of tRNA Related Adenosines Bearing the Hydantoin Ring (ct6A,ms2ct6A) by Intramolecular Cyclization of N6-(N-Boc-α-aminoacyl)-adenosine Derivatives

A novel and efficient way for the synthesis of N⁶-hydantoin-modified adenosines, which utilizes readily available N⁶-(N-Boc-α-aminoacyl)-adenosine derivatives, was developed. The procedure is based on the epimerization-free, Tf₂O-mediated conversion of the Boc group into an isocyanate moiety, followed by intramolecular cyclization. Using this method two recently discovered hydantoin modified tRNA adenosines, that is, cyclic N⁶-threonylcarbamoyl-adenosine ( ct⁶A ) and 2-methylthio-N⁶-threonylcarbamoyladenosine ( ms²ct⁶A ) were prepared in good yields.