Enhanced serum concentrations of transforming growth factor-beta1 in simple fatty liver: is it really benign?

<p>Abstract</p> <p>Background</p> <p>Inside the spectrum of non-alcoholic fatty liver disease, simple fatty liver is generally thought of as being "non progressive", differently from non-alcoholic steatohepatitis, which increases in severity due to the presence of apoptosis/inflammation and fibrosis. The "benignity" of fatty liver is widely accepted but conceptually difficult to maintain because the mechanisms underlying this entity are the same ones that determine the more severe form.</p> <p>Findings provide evidence that iron overload is associated with increased liver damage and collagen deposition. Transforming growth factor-beta1 released by hepatic stellate cells during chronic liver injury plays a critical role in liver apoptosis and fibrogenesis.</p> <p>Objective</p> <p>To verify whether both the forms of non-alcoholic fatty liver disease were really dissimilar, evaluating the serum profile of two key parameters, indexes of severity.</p> <p>Methods</p> <p>A total of 123 patients (57 females) participated, forming three groups: forty five patients with fatty liver, 42 patients with non-alcoholic steatohepatitis and 36 with chronic hepatitis C. All had a biopsy-proven diagnosis.</p> <p>Measurements</p> <p>Serum concentrations of transforming growth factor-beta1 and ferritin.</p> <p>Results</p> <p>High concentrations of transforming growth factor-beta1 were noticed in patients suffering from both fatty liver and non-alcoholic steatohepatitis, 129.1 (45.4) versus 116.8 (42.2) ng/mL, P = 0.2; they were significantly superior to those of chronic hepatitis C patients 87.5 (39.5) ng/mL, P < 0.001. Ferritin levels were on average above normal values and similar in the three groups (P = 0.9), also when adjusted for gender (P = 0.5) and age (P = 0.3).</p> <p>Conclusion</p> <p>No difference between serum concentrations of transforming growth factor-beta1 and ferritin in fatty liver and non-alcoholic steatohepatitis suggests that these forms share more common aspects, regarding their progression, than previously thought.</p

Algebraic Distribution of Segmental Duplication Lengths in Whole-Genome Sequence Self-Alignments

Distributions of duplicated sequences from genome self-alignment are characterized, including forward and backward alignments in bacteria and eukaryotes. A Markovian process without auto-correlation should generate an exponential distribution expected from local effects of point mutation and selection on localised function; however, the observed distributions show substantial deviation from exponential form – they are roughly algebraic instead – suggesting a novel kind of long-distance correlation that must be non-local in origin

Diagnostic accuracy of a noninvasive hepatic ultrasound score for non-alcoholic fatty liver disease (NAFLD) in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

CONTEXT AND OBJECTIVE: Noninvasive strategies for evaluating non-alcoholic fatty liver disease (NAFLD) have been investigated over the last few decades. Our aim was to evaluate the diagnostic accuracy of a new hepatic ultrasound score for NAFLD in the ELSA-Brasil study.DESIGN AND SETTINGS: Diagnostic accuracy study conducted in the ELSA center, in the hospital of a public university.METHODS: Among the 15,105 participants of the ELSA study who were evaluated for NAFLD, 195 individuals were included in this sub-study. Hepatic ultrasound was performed (deep beam attenuation, hepatorenal index and anteroposterior diameter of the right hepatic lobe) and compared with the hepatic steatosis findings from 64-channel high-resolution computed tomography (CT). We also evaluated two clinical indices relating to NAFLD: the fatty liver index (FLI) and the hepatic steatosis index (HSI).RESULTS: Among the 195 participants, the NAFLD frequency was 34.4%. High body mass index, high waist circumference, diabetes and hypertriglyceridemia were associated with high hepatic attenuation and large anteroposterior diameter of the right hepatic lobe, but not with the hepatorenal index. The hepatic ultrasound score, based on hepatic attenuation and the anteroposterior diameter of the right hepatic lobe, presented the best performance for NAFLD screening at the cutoff point &#8805; 1 point; sensitivity: 85.1%; specificity: 73.4%; accuracy: 79.3%; and area under the curve (AUC 0.85; 95% confidence interval, CI: 0.78-0.91)]. FLI and HSI presented lower performance (AUC 0.76; 95% CI: 0.69-0.83) than CT.CONCLUSION: The hepatic ultrasound score based on hepatic attenuation and the anteroposterior diameter of the right hepatic lobe has good reproducibility and accuracy for NAFLD screening

Salmonella enterica Serovar Typhimurium Lacking hfq Gene Confers Protective Immunity against Murine Typhoid

Salmonella enterica is an important enteric pathogen and its various serovars are involved in causing both systemic and intestinal diseases in humans and domestic animals. The emergence of multidrug-resistant strains of Salmonella leading to increased morbidity and mortality has further complicated its management. Live attenuated vaccines have been proven superior over killed or subunit vaccines due to their ability to induce protective immunity. Of the various strategies used for the generation of live attenuated vaccine strains, focus has gradually shifted towards manipulation of virulence regulator genes. Hfq is a RNA chaperon which mediates the binding of small RNAs to the mRNA and assists in post-transcriptional gene regulation in bacteria. In this study, we evaluated the efficacy of the Salmonella Typhimurium Δhfq strain as a candidate for live oral vaccine in murine model of typhoid fever. Salmonella hfq deletion mutant is highly attenuated in cell culture and animal model implying a significant role of Hfq in bacterial virulence. Oral immunization with the Salmonella hfq deletion mutant efficiently protects mice against subsequent oral challenge with virulent strain of Salmonella Typhimurium. Moreover, protection was induced upon both multiple as well as single dose of immunizations. The vaccine strain appears to be safe for use in pregnant mice and the protection is mediated by the increase in the number of CD4+ T lymphocytes upon vaccination. The levels of serum IgG and secretory-IgA in intestinal washes specific to lipopolysaccharide and outer membrane protein were significantly increased upon vaccination. Furthermore, hfq deletion mutant showed enhanced antigen presentation by dendritic cells compared to the wild type strain. Taken together, the studies in murine immunization model suggest that the Salmonella hfq deletion mutant can be a novel live oral vaccine candidate

Biotechnological Perspective of Reactive Oxygen Species (ROS)-Mediated Stress Tolerance in Plants

All environmental cues lead to develop secondary stress conditions like osmotic and oxidative stress conditions that reduces average crop yields by more than 50% every year. The univalent reduction of molecular oxygen (O2) in metabolic reactions consequently produces superoxide anions (O2•−) and other reactive oxygen species (ROS) ubiquitously in all compartments of the cell that disturbs redox potential and causes threat to cellular organelles. The production of ROS further increases under stress conditions and especially in combination with high light intensity. Plants have evolved different strategies to minimize the accumulation of excess ROS like avoidance mechanisms such as physiological adaptation, efficient photosystems such as C4 or CAM metabolism and scavenging mechanisms through production of antioxidants and antioxidative enzymes. Ascorbate-glutathione pathway plays an important role in detoxifying excess ROS in plant cells, which includes superoxide dismutase (SOD) and ascorbate peroxidase (APX) in detoxifying O2•−radical and hydrogen peroxide (H2O2) respectively, monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR) and glutathione reductase (GR) involved in recycling of reduced substrates such as ascorbate and glutathione. Efficient ROS management is one of the strategies used by tolerant plants to survive and perform cellular activities under stress conditions. The present chapter describes different sites of ROS generation and and their consequences under abiotic stress conditions and also described the approaches to overcome oxidative stress through genomics and genetic engineering