Predictors of hepatitis B surface antigen loss,relapse and retreatment after discontinuation of effective oral antiviral therapy in noncirrhotic HBeAg‐negative chronic hepatitis B

Reliable predictors of outcomes after treatment discontinuation in HBeAg‐negative chronic hepatitis B (CHB) patients have not been established. We investigated the role of hepatitis B surface antigen (HBsAg), interferon‐inducible protein‐10 (IP10) and hepatitis B core‐related antigen (HBcrAg) serum levels as predictors of HBsAg loss, relapse and retreatment in noncirrhotic HBeAg‐negative CHB patients who discontinued long‐term antiviral therapy. All HBsAg‐positive (n = 57) patients of the prospective DARING‐B study were included and followed monthly for 3 months, every 2/3 months until month‐12 and every 3/6 months thereafter. HBsAg, IP10 and HBcrAg levels were measured by enzyme immunoassays, and SCALE‐B score was calculated. Twelve patients achieved HBsAg loss before retreatment with 18‐month cumulative incidence of 25%. Independent predictors of HBsAg loss were baseline HBsAg and month‐1 IP10 levels. Of 10 patients with baseline HBsAg ≤100 IU/mL, 70% cleared HBsAg and 10% required retreatment. Of 23 patients with baseline HBsAg >1000 IU/mL, 4% cleared HBsAg and 43% required retreatment. Of 24 patients with intermediate baseline HBsAg (100‐1000 IU/mL), 17% cleared HBsAg and 21% required retreatment; in this subgroup, month‐1 IP10 was significantly associated with HBsAg loss, which occurred in 30% and 7% of cases with IP10 >150 and ≤150 pg/mL, respectively. Baseline HBcrAg was undetectable in all patients who cleared HBsAg and was associated with retreatment. SCALE‐B was associated with HBsAg loss but not with relapse or retreatment. In conclusion, HBsAg, IP10 and HBcrAg serum levels can be useful for the decisions and management of treatment discontinuation in noncirrhotic Caucasian patients with HBeAg‐negative CHB.     

A low molecular weight OLED material: 2-(4-((2-hydroxyethyl)(methyl)amino)benzylidene)malononitrile. Synthesis,crystal structure,thin film morphology,spectroscopic characterization and DFT calculations

2-(4-((2-Hydroxyethyl)(methyl)amino)benzylidene)malononitrile (HEMABM) was synthesized from 4-[hydroxymethyl(methyl)amino]benzaldehyde and propanedinitrile to obtain a low molecular weight fluorescent material with an efficient solid-state emission and electroluminescence properties comparable to the well-known poly(2-methoxy-5(2′-ethyl)hexoxyphenylenevinylene) (MEH-PPV). The HEMABM was used to prepare an organic light-emitting diode by a solution process. Despite the title compound being a small molecule, it showed optical properties and notable capacity to form a film with smooth morphology (10.81 nm) closer to that of polymer MEH-PPV (10.63 nm). The preparation of the device was by spin coating, the electrical properties such as threshold voltage were about 1.0 V for both HEMABM and MEH-PPV, and the luminance 1300 cd m⁻² for HEMABM and 2600 cd m⁻² for MEH-PPV. This low molecular weight compound was characterized by SCXRD, IR, NMR, and EI. Besides a quantitative analysis of the intermolecular interactions by PIXEL, density functional theory (DFT) calculations are reported.

A low molecular weight fluorescent malononitrile derivative showed an efficient solid-state emission and electroluminescence properties.     

Complex Deregulation and Expression of Cytokines and Mediators of the Immune Response in Parkinson's Disease Brain is Region Dependent

Neuroinflammation is common in neurodegenerative diseases including Parkinson disease (PD). Expression of 25 mRNAs was assessed with TaqMan‐PCR including members of the complement system, colony stimulating factors, Toll family, cytokines IL‐8, IL‐6, IL‐6ST, IL‐1B, TNF‐α family, IL‐10, TGFβ family, cathepsins and integrin family, in the substantia nigra pars compacta, putamen, frontal cortex area 8 and angular gyrus area 39, in a total of 43 controls and 56 cases with PD‐related pathology covering stages 1–6 of Braak. Up‐regulation of IL‐6ST was the only change in the substantia nigra at stages 1–2. Down‐regulation of the majority of members examined occurred in the substantia nigra from stage 4 onwards. However, region‐dependent down‐ and up‐regulation of selected mRNAs occurred in the putamen and frontal cortex, whereas only mRNA up‐regulated mRNAs were identified in the angular cortex from stage 3 onwards in PD cases. Protein studies in frontal cortex revealed increased IL6 expression and reduced IL‐10 with ELISA, and increased IL‐6 with western blotting in PD. Immunohistochemistry revealed localization of IL‐5, IL‐6 and IL‐17 receptors in glial cells, mainly microglia; IL‐5, IL‐10 and M‐CSF in neurons; TNF‐α in neurons and microglia; and active NF‐κB in the nucleus of subpopulations of neurons and glial cells in PD. Distinct inflammatory responses, involving pro‐ and anti‐inflammatory cytokines, and variegated mediators of the immune response occur in different brain regions at the same time in particular individuals. Available information shows that altered α‐synuclein solubility and aggregation, Lewy body formation, oxidative damage and neuroinflammation converge in the pathogenesis of PD.     

Bennett acceptance ratio method to calculate the binding free energy of BACE1 inhibitors: Theoretical model and design of new ligands of the enzyme

In recent years, the design, development, and evaluation of several inhibitors of the BACE1 enzyme, as part of Alzheimer's treatment, have gathered the scientific community's interest. Here, a linear regression model was built using binding free energy calculations through the Bennett acceptance ratio method for 20 known inhibitors of the BACE1 enzyme, with a Pearson coefficient of R = 0.88 and R² = 0.78. The validation of this model was verified employing eight additional random inhibitors, which also gave a linear correlation with R = 0.97 and R² = 0.93. Furthermore, this linear regression model was also used for proposing the structure of four potential BACE1 inhibitors, and the most active of them gave a theoretical K_d = 10 nM. However, these molecules have not been synthesized yet. Our team used a total time of more than 800 ns for the Molecular Dynamics to carry out this study, and all the software used were freely available.     

Peliosis hepatis complicated by portal hypertension following renal transplantation

Peliosis hepatis is a rare benign disease, but in last years the number of identified cases has increased. This disease is known to be sometimes accompanied by hepatocellular carcinoma. In the recent article, Yu et al describe a case of liver peliosis, characterized by an increased proliferative index. Therefore, additional diagnosis of patients should include analyzing other tumor markers expression in order to assess the risk of malignant cell transformation in peliosis hepatis.     

Applied research in biotechnology as a source of opportunities for green chemistry start-ups

Applied research in biotechnology can be a source of inspiration for start-ups in green chemistry. The versatility of bioprocesses and the possibility of developing business models from research outcomes could create innovation ecosystems, including large economies and developing countries such as Colombia.The process of training young researchers is key to ensure the feasibility of these start-ups in the long term; however, many universities have curricula that are far from generating conditions that favor the development of new businesses. The integration between research groups, curriculum, and the industry are key elements to deepen the development of green chemistry-oriented ventures.This paper shows the lessons learned from Universidad Pontificia Bolivariana through its research group in biotechnology CIBIOT as a working model that integrates the curriculum and research. Case studies and reflections on technology-based entrepreneurship are shown.