Non-alcoholic Fatty Liver Disease: What We Learn from Omics Studies

Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver diseases with 10–30% prevalence in western countries. The severity of NAFLD ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC). However, the wide range of clinical staging of the disease prevents the clear understanding of its pathogenesis. Recently, high-throughput genomic, transcriptomic, and proteomic studies focus on enlightening the complex mechanisms responsible for NAFLD and NASH development. All together these Omics studies, in different cohorts once again, proved that NAFLD and NASH are linked with many complex mechanisms such as accumulation and traffic of various lipids in the liver and activation of inflammation responses. Moreover, some of these studies may have identified potential biomarkers and candidate risky or protective alleles that can be a valuable tool for the assessment of susceptibility and histological severity of NAFLD. Nonetheless, confirmation of these potential biomarkers and candidate genes by multiple Omics tools is required for their clinical application in the diagnosis and treatment of NASH and NAFLD

Can Proteomic Profiling Identify Biomarkers and/or Therapeutic Targets for Liver Fibrosis?

Liver fibrosis is a serious disease that affects around 350–400 million people worldwide. The main approach for fibrosis staging is liver biopsy, which is an invasive procedure that is not endured pretty well by patients. Currently, some serum-based biomarker panels are available for diagnosis and staging of liver fibrosis. Recent high-throughput proteomic studies are also very promising for identification of novel biomarkers for diagnosis and/or treatment of liver fibrosis. We hereby review the application of proteomic profiling studies for identification of fibrosis biomarkers with their advantages and drawbacks

Longitudinal metabolomics analysis reveals the acute effect of cysteine and NAC included in the combined metabolic activators

Growing evidence suggests that the depletion of plasma NAD+ and glutathione (GSH) may play an important role in the development of metabolic disorders. The administration of Combined Metabolic Activators (CMA), consisting of GSH and NAD+ precursors, has been explored as a promising therapeutic strategy to target multiple altered pathways associated with the pathogenesis of the diseases. Although studies have examined the therapeutic effect of CMA that contains N-acetyl-L-cysteine (NAC) as a metabolic activator, a system-wide comparison of the metabolic response to the administration of CMA with NAC and cysteine remains lacking. In this placebo-controlled study, we studied the acute effect of the CMA administration with different metabolic activators, including NAC or cysteine with/without nicotinamide or flush free niacin, and performed longitudinal untargeted-metabolomics profiling of plasma obtained from 70 well-characterized healthy volunteers. The time-series metabolomics data revealed the metabolic pathways affected after the administration of CMAs showed high similarity between CMA containing nicotinamide and NAC or cysteine as metabolic activators. Our analysis also showed that CMA with cysteine is well-tolerated and safe in healthy individuals throughout the study. Last, our study systematically provided insights into a complex and dynamics landscape involved in amino acid, lipid and nicotinamide metabolism, reflecting the metabolic responses to CMA administration containing different metabolic activators

Concentrations of Connective Tissue Growth Factor in Patients with Nonalcoholic Fatty Liver Disease: Association with Liver Fibrosis

Aim: In this study, we aimed to investigate the relationship between the histological fibrosis stage of nonalcoholic fatty liver disease (NAFLD) and serum connective tissue growth factor (CTGF) to determine the usefulness of this relationship in clinical practice. Methods: Serum samples were collected from 51 patients with biopsy-proven NAFLD and 28 healthy controls, and serum levels of CTGF were assayed by ELISA. Results: Levels of CTGF were significantly higher in patients with NAFLD compared with controls (P = 0.001). The serum CTGF levels were significantly increased, that correlated with histological fibrosis stage, in patients with NAFLD [in patients with no fibrosis (stage 0) 308.2 ± 142.9, with mild fibrosis (stage 1–2) 519.9±375.2 and with advanced fibrosis (stage 3–4) 1353.2 ± 610 ng/l, P < 0.001]. Also serum level of CTGF was found as an independent predictor of histological fibrosis stage in patients with NAFLD (β = 0.662, t = 5.6, P < 0.001). The area under the ROC curve was estimated 0.931 to separate patients with severe fibrosis from patients with other fibrotic stages. Conclusion: Serum levels of CTGF may be a clinical utility for distinguishing NAFLD patients with and without advanced fibrosis

Real-world efficacy and safety of Ledipasvir plus Sofosbuvir and Ombitasvir/Paritaprevir/Ritonavir +/- Dasabuvir combination therapies for chronic hepatitis C: A Turkish experience

Background/Aims: This study aimed to evaluate the real-life efficacy and tolerability of direct-acting antiviral treatments for patients with chronic hepatitis C (CHC) with/without cirrhosis in the Turkish population.Material and Methods: A total of 4,352 patients with CHC from 36 different institutions in Turkey were enrolled. They received ledipasvir (LDV) and sofosbuvir (SOF)+/- ribavirin (RBV) ombitasvir/paritaprevir/ritonavir +/- dasabuvir (PrOD)+/- RBV for 12 or 24 weeks. Sustained virologic response (SVR) rates, factors affecting SVR, safety profile, and hepatocellular cancer (HCC) occurrence were analyzed.Results: SVR12 was achieved in 92.8% of the patients (4,040/4,352) according to intention-to-treat and in 98.3% of the patients (4,040/4,108) according to per-protocol analysis. The SVR12 rates were similar between the treatment regimens (97.2%-100%) and genotypes (95.6%-100%). Patients achieving SVR showed a significant decrease in the mean serum alanine transaminase (ALT) levels (50.90 +/- 54.60 U/L to 17.00 +/- 14.50 U/L) and model for end-stage liver disease (MELD) scores (7.51 +/- 4.54 to 7.32 +/- 3.40) (p<0.05). Of the patients, 2 were diagnosed with HCC during the treatment and 14 were diagnosed with HCC 37.0 +/- 16.0 weeks post-treatment. Higher initial MELD score (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.22-2.38; p=0.023]), higher hepatitis C virus (HCV) RNA levels (OR: 1.44, 95% CI: 1.31-2.28; p=0.038), and higher serum ALT levels (OR: 1.38, 95% CI: 1.21-1.83; p=0.042) were associated with poor SVR12. The most common adverse events were fatigue (12.6%), pruritis (7.3%), increased serum ALT (4.7%) and bilirubin (3.8%) levels, and anemia (3.1%).Conclusion: LDV/SOF or PrOD +/- RBV were effective and tolerable treatments for patients with CHC and with or without advanced liver disease before and after liver transplantation. Although HCV eradication improves the liver function, there is a risk of developing HCC.Turkish Association for the Study of The Liver (TASL

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2

Ferrofluid plug actuation for Micro pumping systems

© 2017 Trans Tech Publications, Switzerland.Ferrofluids are colloidal mixtures which consist of nano-sized magnetic particles suspended in a base fluid. The typical magnetic particles could be maghemite, magnetite, cobalt ferrite etc. To keep a ferrofluid suspension in a stable state is possible by an electrical double layer or by adding surfactant. They have many applications on electrical, mechanical and optical systems. Recently, the ability of being manipulated by an external magnetic field made them considerable for microfluidic systems such as micro operations, pumping and mixing. Among them, micro scaled pumping systems have appeared as a critical research area due to its notable potential to be applied on many biological and electronic systems. Moreover, the development of lab on a chip and the micro total analysis systems for biological issues has revealed the necessity of liquid transport for micro quantities. Micropumps with ferrofluid plug actuation mechanisms are considered to have the ability to fulfill this requirement. Therefore, driving the working fluids with ferrofluid plugs in a micro-sized tube or channel has attracted researchers' interest. In this study, ferrofluid plug actuated micro pumping systems have been reviewed from the available literature based on their design and their maximum generated flow rate

Magnetic field dependent thermal conductivity measurements of magnetic nanofluids by 3 omega method

This study aims to investigate the thermal conductivity of the Fe3O4-water magnetic nanofluid under the influence of external magnetic field. The Fe3O4-water magnetic nanofluid sample with 4.8% vol. concentration was purchased. Then, it is diluted to four different vol. concentrations of 1, 2, 3, 4%. The external magnetic field in the range of 0-400 G was applied in parallel and perpendicular directions to the temperature gradient generated by the thermal conductivity measurement probe. Before thermal conductivity measurements, the external magnetic field generated in the air gap between permanent magnets has been analyzed both numerically and experimentally. Then a non-uniformity parameter was defined to relate magnetic field in measurement region to chain aggregation of the nanoparticles. Thermal conductivity measurements were conducted with 3 omega method. The results showed that the thermal conductivity enhances with the increasing of the magnetic field strength up to a specific point, then the enhancement decreases. It is also observed that this specific point varies according to the particle concentration. Unlike the most of available study in the literature, in this study the lower thermal conductivity enhancements were obtained. The maximum enhancements with the highest concentration were 10% and 5.6% in parallel and perpendicular orientations, respectively

A rotating permanent magnetic actuator for micropumping devices with magnetic nanofluids

In this study, a novel rotating permanent magnetic actuator (PMA) system is proposed to manipulate magnetic nanofluids to pump chemicals inside micro-sized channels with circular paths. The PMA consists of two permanent magnet pairs and a rotor-like structure. A semicircular-shaped microchannel with a square cross-section area is located at the top of the actuator in order to investigate the performance of the PMA. Fe3O4-water magnetic nanofluid is employed as a working fluid for the manipulation inside the microchannel. In the first stage of this work, a numerical survey is conducted to determine the most suitable angular distance between permanent magnets of a pair in terms of generated magnetic field form in the microchannel region and velocity distribution of magnetic nanofluid within the semicircular microchannel when the permanent magnets are stationary. Preliminary experiments are then carried out for the stationary permanent magnets to validate the predicted flow-field results. Performance tests for different PMA speeds (7.5-30 rpm) and particle concentrations (1%-3% by vol.) indicate that it is possible to manipulate the magnetic nanofluid inside the semicircular channel within a velocity range of 58.7-940 mu m s(-1), which corresponds to a flow rate range of 0.56-9.02 mu L min(-1). The results confirm that the proposed PMA system provides flow rate requirements in analytical microfluidic applications such as low flow drug delivery (1-10 mu L min(-1)), cell sorting (6.1 mu L min(-1)), and pathogen detection (3-5.83 mu L min(-1))