Interleukin 10 promoter haplotype is associated with alcoholic liver cirrhosis in Taiwanese patients

AbstractAlcoholic liver cirrhosis is a severe form of alcohol-related liver damage. More than 95% of heavy drinkers develop a fatty liver, but only 35% of them develop cirrhosis. We postulate that genetic factors may play a role in this difference. Genetic polymorphisms of the cytokine genes may influence Kupffer cells cytokine genes expression. In this study, we evaluated the promoter polymorphisms of interleukin (IL) 1β, IL 6, IL 10, and tumor necrosis factor alpha (TNFα) and aimed to clarify the association between the polymorphisms and the disease. Forty alcoholic patients with liver cirrhosis and 64 healthy volunteers were included in our investigation. Genotyping on IL 1β –511 T>C, IL 6 –572 G>C, IL 10 –819 C>T, IL 10 –1082 G>A, and TNFα –308 G>A was done. Another 36 patients with recurrent alcoholic pancreatitis were included as an additional control group. Genotyping on IL 10 –819 C>T and IL 10 –1082 G>A was done. The polymorphisms on IL 1 and IL 6 showed no significant association. The p value for TNFα –308 G>A was 0.028 in comparison with healthy volunteers. Although the p value was less than 0.05, it did not reach significance after Bonferroni correction. The p values for IL 10 –819 C>T and IL 10 –1082 G>A were respectively 0.031 and 0.026 in healthy volunteers and 0.028 and 0.023 in the alcoholic pancreatitis group. The results also did not reach significance after Bonferroni correction. Among the participants with the GCC haplotype, healthy volunteers had p = 0.027 (p < 0.05) and an odds ratio (OR) of 0.124 [confidence interval (95%) CI, 0.015–0.997], whereas the alcoholic pancreatitis group had p = 0.023 (p < 0.05) and an OR of 0.106 (95% CI, 0.012–0.912). The odds ratio of people having one ATA haplotype was 6.233 (95% CI, 0.739–52.547) in healthy volunteers and 6.588 (95% CI, 0.727–59.679) in the alcoholic pancreatitis group; the corresponding rate was 10.521 (95% CI, 1.252–88.440) and 12.833 (95% CI 1.408–117.008) for people with two ATA haplotypes. The p values in these groups were 0.031 (p < 0.05) and 0.028 (p < 0.05), respectively. The presence of a GCC haplotype could have protective effect against alcoholic liver disease, whereas the presence of an ATA haplotype could predispose carriers to the disease. The IL 10 promoter haplotype is associated with alcoholic liver cirrhosis in Taiwanese patients

Эволюция наноструктурированных продуктов индивидуального электрохимического окисления меди и алюминия

This paper covers the results of the composition and structure evolution of nanostructured materials produced by separate electrochemical oxidation of metals (copper and aluminum). The electrolysis products after short-term and long-term aging were characterized by XRD (X‑ray diffraction) and DSC (differential scanning calorimetry) analysis. There is the difference in aging of nanostructures of copper- and aluminum-compounds. Short-term aging results in the phase transformation of copper (I) oxide and the stability of aluminum oxyhydroxide (boehmite). Copper (I) oxide is oxidized to copper (II) oxide and copper carbonate hydroxide. At long-term aging the oxidation of copper (I) oxide does not completed because the Pilling–Bedworth ratio for copper (II) oxide, copper carbonate hydroxide is greater than one. The structure of all copper-containing compounds (copper (I) oxide, copper (II) oxide, copper carbonate hydroxide) is changed. It results in the increases of both the interplanar spacing and the temperature of the phase transformations. Coherent scattering region (CSR) of boehmite and copper (I) oxide are 3–4 nm and 20–30 nm, respectively, and does not change at short-term and long-term agingВ работе представлены результаты исследования эволюции состава и структуры наноструктурированных материалов, полученных при раздельном электрохимическом окислении металлов (медь и алюминий). Продукты электролиза после кратковременного и длительного старения охарактеризованы методами РФА (рентгенофазовый анализ) и ДСК (дифференциальная сканирующая калориметрия). Установлено различие в старении наноструктур соединений меди и алюминия. Кратковременное старение приводит к фазовому превращению оксида меди (I) и стабильности оксигидроксида алюминия (бемита). Оксид меди (I) окисляется до оксида меди (II) и основного карбоната меди. При длительном старении оксида меди (I) окисление происходит не полностью, так как отношения Пиллинга-Бедворта для оксида меди (II) и гидроксида карбоната меди больше единицы. Структура всех медьсодержащих соединений (оксид меди (I), оксид меди (II), гидроксид карбоната меди) изменяется. Это приводит к увеличению как межплоскостных расстояний, так и температуры фазовых превращений. Область когерентного рассеяния (ОКР) бемита и оксида меди (I) составляет 3–4 нм и 20–30 нм, соответственно, и не изменяется при кратковременном и длительном старени

Molecular basis of USP7 inhibition by selective small-molecule inhibitors

Ubiquitination controls the stability of most cellular proteins, and its deregulation contributes to human diseases including cancer. Deubiquitinases remove ubiquitin from proteins, and their inhibition can induce the degradation of selected proteins, potentially including otherwise 'undruggable' targets. For example, the inhibition of ubiquitin-specific protease 7 (USP7) results in the degradation of the oncogenic E3 ligase MDM2, and leads to re-activation of the tumour suppressor p53 in various cancers. Here we report that two compounds, FT671 and FT827, inhibit USP7 with high affinity and specificity in vitro and within human cells. Co-crystal structures reveal that both compounds target a dynamic pocket near the catalytic centre of the auto-inhibited apo form of USP7, which differs from other USP deubiquitinases. Consistent with USP7 target engagement in cells, FT671 destabilizes USP7 substrates including MDM2, increases levels of p53, and results in the transcription of p53 target genes, induction of the tumour suppressor p21, and inhibition of tumour growth in mice