Efficacy of pegylated interferon α2a in patients without HBeAg loss after the withdrawal of long-term lamivudine therapy

BACKGROUND: Improving the HBe seroconversion rate of patients without HBeAg loss after long-term lamivudine therapy has become an urgent clinical problem that we have to face. Unfortunately, there is no consensus on the mananement of these patients. The aim of this study was to evaluate the efficacy of pegylated interferon (PEG-IFN) α2a in patients without HBeAg loss after the withdrawal of long-term lamivudine therapy. METHODS: Fifty patients with chronic hepatitis B without the loss of HBeAg after ≥96 weeks of lamivudine treatment were enrolled to withdraw from treatment to induce a biochemical breakthrough. Patients who achieved a biochemical breakthrough within 24 weeks received 48-weeks of PEG-IFN α2a therapy, and were then assessed during a subsequent 24-week follow-up period. RESULTS: Forty-three (86.0%) patients achieved a biochemical breakthrough within 24 weeks of lamivudine withdrawal. The rates of combined response (both undetectable HBV DNA and HBeAg loss) and HBsAg loss were alone 51.2% and 20.9%, respectively after 48 weeks of PEG-IFN α2a therapy, and 44.2% and 18.6%, respectively, at 24 weeks after treatment cessation. The end-of-treatment combined response rate was 65.4% among patients with a baseline HBsAg <20,000 IU/mL, which was significantly higher than 29.4% of patients with HBsAg ≥20,000 IU/mL (P=0.031). For patients with HBsAg levels <1,500 IU/mL at 12 and 24 weeks therapy, the end-of-treatment combined response rate was 68.2% and 69.0%, which were both significantly higher than patients with HBsAg ≥1,500 IU/mL (33.3% and 14.3%; P=0.048 and 0.001). The end-of-treatment combined response rate was significantly higher among patients with HBV DNA<10(5) copies/mL (76.2%) compared to patients with HBV DNA ≥10(5) copies/mL (27.3%) after 24 weeks of therapy (P=0.004). CONCLUSION: Retreatment with PEG-IFN α2a was effective and safe for patients without HBeAg loss after the withdrawal of long-term lamivudine therapy. HBsAg levels at the baseline, 12 and 24 weeks of therapy, and HBV DNA levels at 24 weeks of therapy, can predict the effect of PEG-IFN α2a after 48 weeks of therapy

2,3,4,6-Tetra-O-acetyl-β-d-galacto­pyrano­syl butyrate

The title compound, C18H26O11, was synthesized by a condensation reaction of 2,3,4,6-tetra-O-acetyl-α-d-galactopyranosyl bromide and butyric acid. The acet­oxy­methyl and butyrate groups are located on the same side of the pyran ring, showing the β configuration for the d-glycosyl ester; the butyl group adopts an extend conformation, the C—C—C—C torsion angle being 179.1 (7)°. In the crystal, the mol­ecules are linked by weak C—H⋯O hydrogen bonds

(Acetyl­acetonato-κ2 O,O′)bis­[2-(5-methyl-3-phenyl­pyrazin-2-yl-κN 1)phen­yl-κC 1]iridium(III)

In the title complex, [Ir(C17H13N2)2(C5H7O2)], the IrIII atom is hexa­coordinated in a distorted octa­hedral geometry by two C,N-bidentate 2-(5-methyl-3-phenyl­pyrazin-2-yl)phenyl (mdpp) ligands and one O,O-bidentate acetyl­acetonate ligand. The dihedral angles between the phenyl rings and the pyrazine ring are 9.56 (14) and 58.99 (14)° for one mdpp ligand and 9.34 (14) and 79.94 (15)° for the other

Elevation of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Expression in the Mouse Brain after Chronic Nonylphenol Exposure

The present study was performed to investigate the effects of chronic administration of nonylphenol (NP) on the expression of inflammation-related genes in the brains of mice. NP was given orally by gavages at 0, 50, 100, and 200 mg/kg/d. The expression of inflammatory enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), was evaluated by immunohistochemistry and immunoblotting assays. The nitric oxide (NO) level and nitric oxide synthase (NOS) activity were also measured by biochemical analyses. The results showed that NP at a high dose (200 mg/kg/d) significantly increased the expression of iNOS and COX-2 in both the hippocampus and cortex. In parallel with the increase in iNOS expression, the NO level was significantly greater at the dose of 200 mg/kg/d, compared to the control. The activity of NOS was also increased in the brain of mice at the dose of 100 and 200 mg/kg/d. These findings demonstrate that NP may have the potential to induce the chronic inflammation or cause neurotoxicity in the mouse brain

Comprehensive Analysis of CRIP1 Expression in Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy that imposes great challenges in terms of drug resistance and relapse. Previous studies revealed heterogeneous leukemia cells and their relevant gene markers, such as CRIP1 as clinically prognostic in t (8;21) AML patients. However, the expression and role of CRIP1 in AML are poorly understood. We used the single-cell RNA sequencing and gene expression data from t (8;21) AML patients to analyze the immune and regulation networks of CRIP1. Two independent cohorts from GSE37642 and The Cancer Genome Atlas (TCGA) datasets were employed as validation cohorts. In addition, the methylation data from TCGA were used to analyze the methylation effect of the CRIP1 expression. Gene expression profile from t (8;21) AML patients showed that the CRIP1-high group exhibited an enrichment of immune-related pathways, including tumor necrosis factor (TNF)α signaling via nuclear factor kappa B (NFκB) pathways. Further studies using CIBERSORT showed that the CRIP1-high group had a significantly higher infiltration of exhausted CD8 T cells and activated mast cells. The CRIP1 expression was validated in the GSE37642-GPL96, GSE37642-GPL570, and TCGA datasets. In addition, with the methylation data, four CpG probes of CRIP1 (cg07065217, cg04411625, cg25682097, and 11763800) were identified as negatively associated with the CRIP1 gene expression in AML patients. Our data provide a comprehensive overview of the regulation of CRIP1 expression in AML patients. The evaluation of the TNFα-NFκB signaling pathway as well as the immune heterogeneity might provide new insights for exploring improvements in AML treatment

Insights into the Ecological Roles and Evolution of Methyl-Coenzyme M Reductase-Containing Hot Spring Archaea

Several recent studies have shown the presence of genes for the key enzyme associated with archaeal methane/alkane metabolism, methyl-coenzyme M reductase (Mcr), in metagenome-assembled genomes (MAGs) divergent to existing archaeal lineages. Here, we study the mcr-containing archaeal MAGs from several hot springs, which reveal further expansion in the diversity of archaeal organisms performing methane/alkane metabolism. Significantly, an MAG basal to organisms from the phylum Thaumarchaeota that contains mcr genes, but not those for ammonia oxidation or aerobic metabolism, is identified. Together, our phylogenetic analyses and ancestral state reconstructions suggest a mostly vertical evolution of mcrABG genes among methanogens and methanotrophs, along with frequent horizontal gene transfer of mcr genes between alkanotrophs. Analysis of all mcr-containing archaeal MAGs/genomes suggests a hydrothermal origin for these microorganisms based on optimal growth temperature predictions. These results also suggest methane/alkane oxidation or methanogenesis at high temperature likely existed in a common archaeal ancestor