Search

Nonalcoholic fatty liver disease (NAFLD) refers to excess fat accumulation in the liver. In animal experiments and human kinetic study, we found that administration of combined metabolic activators (CMAs) promotes the oxidation of fat, attenuates the resulting oxidative stress, activates mitochondria, and eventually removes excess fat from the liver. Here, we tested the safety and efficacy of CMA in NAFLD patients in a placebo-controlled 10-week study. We found that CMA significantly decreased hepatic steatosis and levels of aspartate aminotransferase, alanine aminotransferase, uric acid, and creatinine, whereas found no differences on these variables in the placebo group after adjustment for weight loss. By integrating clinical data with plasma metabolomics and inflammatory proteomics as well as oral and gut metagenomic data, we revealed the underlying molecular mechanisms associated with the reduced hepatic fat and inflammation in NAFLD patients and identified the key players involved in the host-microbiome interactions. In conclusion, we showed that CMA can be used to develop a pharmacological treatment strategy in NAFLD patients., Knut and Alice Wallenberg Foundation; European Union (EU); Horizon 2020; PoLiMeR Innovative Training Network; Marie Sklodowska-Curie Grant; Research and Innovation Program

Introduction: socioeconomic factors play an important role in the prevalence of Helicobacter pylori (HP) infection. The aim of this study is to investigate HP prevalence among symptomatic patients in the upper socioeconomic segment of the population undergoing gastroscopy in an endemic urban region. Methodology: over a 12-month period, data were collected from the first consecutive 1000 patients (500 from university hospital, 500 from community hospital) who had gastroscopy and HP evaluation. Results: overall, 211/1000 patients (21.1 %) were found to have HP in gastric biopsies. The specificity, sensitivity, positive predictive value, negative predictive value and diagnostic accuracy of rapid urease test were 87.5%, 99.7%, 99%, 96.5%, and 96.9% respectively. Atrophic gastritis, gastric and duodenal ulcers were significantly more common in HP positive patients. Age based distribution of HP prevalence: > 6 decades (15.5%), 3rd-5th decades (26.1%), < 3rd decades (10.4%). Conclusion: in an HP endemic country, the prevalence of HP infection among symptomatic patients belonging to the upper socioeconomic segment of the population appears to be markedly lower. The lowest prevalence in young patients is expected to result in future decrease in HP prevalence., NA

NA

Fabrication and characterization of flexible optical fiber bundles (FBs) with in-house synthesized high-index and low-index thermally matched glasses are presented. The FBs composed of around 15000 single-core fibers with pixel sizes between 1.1 and 10 mu m are fabricated using the stack-and-draw technique from sets of thermally matched zirconium-silicate ZR3, borosilicate SK222, sodium-silicate K209, and F2 glasses. With high refractive index contrast pair of glasses ZR3/SK222 and K209/F2, FBs with numerical apertures (NAs) of 0.53 and 0.59 are obtained, respectively. Among the studied glass materials, ZR3, SK222, and K209 are in-house synthesized, while F2 is commercially acquired. Seven different FBs with varying pixel sizes and bundle diameters are characterized. Brightfield imaging of a micro-ruler and a Convallaria majalis sample and fluorescence imaging of a dye-stained paper tissue and a cirrhotic mice liver tissue are demonstrated using these FBs. demonstrating their good potential for microendoscopic imaging. Brightfield and fluorescence imaging performance of the studied FBs are compared. For both sets of glass compositions, good imaging performance is observed for FBs, with core diameter and core-to-core distance values larger than 1.6 mu m and 2.3 mu m, respectively. FBs fabricated with K209/F2 glass pairs revealed better performance in fluorescence imaging due to their higher NA of 0.59., Smart Growth Operational Programme; EU-H2020-ICT-2014 grant MIREGAS: Programmable multi-wavelength Mid-IR source for gas sensing; Foundation for Polish Science Team Programme; European Regional Development Fund; European Union (European Union); H2020

Non-alcoholic fatty liver disease (NAFLD) is caused by the imbalance between lipid deposition and lipid removal from the liver, and its global prevalence continues to increase dramatically. NAFLD encompasses a spectrum of pathological conditions including simple steatosis and non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis and liver cancer. Even though there is a multi-disciplinary effort for development of a treatment strategy for NAFLD, there is not an approved effective medication available. Single or combined metabolic cofactors can be supplemented to boost the metabolic processes altered in NAFLD. Here, we review the dosage and usage of metabolic cofactors including l-carnitine, Nicotinamide riboside (NR), l-serine, and N-acetyl-l-cysteine (NAC) in human clinical studies to improve the altered biological functions associated with different human diseases. We also discuss the potential use of these substances in treatment of NAFLD and other metabolic diseases including neurodegenerative and cardiovascular diseases of which pathogenesis is linked to mitochondrial dysfunction., Knut and Alice Wallenberg Foundation

Background: Extra-oesophageal reflux (EOR) may lead to microaspiration in patients with cystic fibrosis (CF), a probable cause of deteriorating lung function. Successful clinical trials of ivacaftor highlight opportunities to understand EOR in a real world study. Methods: Data from 12 patients with CF and the G551D mutation prescribed ivacaftor (150 mg bd) was collected at baseline, 6, 26 and 52 weeks. The changes in symptoms of EOR were assessed by questionnaire (reflux symptom index (RSI) and Hull airway reflux questionnaire (HARQ)). Results: Six patients presented EOR at baseline (RSI > 13; median 13; range 2-29) and 5 presented airway reflux (HARQ >13; median 12; range 3 to 33). Treatment with ivacaftor was associated with a significant reduction of EOR symptoms (P < 0.04 versus baseline) denoted by the reflux symptom index and Hull airway reflux questionnaire. Conclusion: Ivacaftor treatment was beneficial for patients with symptoms of EOR, thought to be a precursor to microaspiration., BBSRC; UK Government Technology Strategy Board Knowledge Transfer Partnership; Medical Research Council Clinician Scientist Fellowship

NA

Background: Chronic hepatitis B infection is characterized by hepatic immune and inflammatory response with considerable variation in the rates of progression to cirrhosis. Genetic variants and environmental cues influence predisposition to the development of chronic liver disease; however, it remains unknown if aberrant DNA methylation is associated with fibrosis progression in chronic hepatitis B. Results: To identify epigenetic marks associated with inflammatory and fibrotic processes of the hepatitis B-induced chronic liver disease, we carried out hepatic genome-wide methylation profiling using Illumina Infinium beadarrays comparing mild and severe fibrotic disease in a discovery cohort of 29 patients. We obtained 310 differentially methylated regions and selected four loci comprising three genes from the top differentially methylated regions: hypermethylation of HOXA2 and HDAC4 along with hypomethylation of PPP1R18 were significantly linked to severe fibrosis. We replicated the prominent methylation marks in an independent cohort of 102 patients by bisulfite modification and pyrosequencing. The timing and causal relationship of epigenetic modifications with disease severity was further investigated using a cohort of patients with serial biopsies. Conclusions: Our findings suggest a linkage of widespread epigenetic dysregulation with disease progression in chronic hepatitis B infection. Cpg methylation at novel genes sheds light on new molecular pathways, which can be potentially exploited as a biomarker or targeted to attenuate inflammation and fibrosis., European Association for the Study of the Liver; Sheila Sherlock Physician Scientist Fellowship; European Commission; Horizon Marie Curie Sklodowska Individual Fellowship; NIHR Newcastle Biomedical Research Centre

Background: Chronic liver injury can lead to the development of liver fibrosis and cirrhosis but only in a minority of patients. Currently, it is not clear which factors determine progression to fibrosis. We investigated whether DNA\methylation profile as determined by pyrosequencing can distinguish patients with mild from those with advanced/severe fibrosis in non-alcoholic liver disease (NAFLD) and alcoholic liver disease (ALD). To this end, paraffin-embedded liverbiopsies were collected from patients with biopsy-proven NAFLD or ALD, as well as paraffin-embedded normal liver resections, genomic DNA isolated, bisulfite converted and pyrosequencing assays used to quantify DNA methylation at specific CpGs within PPAR alpha, PPAR alpha, TGF beta 1, Collagen 1A1 and PDGF alpha genes. Furthermore, we assessed the impact of age, gender and anatomical location within the liver on patterns of DNA methylation inthe same panel of genes. Results: DNA methylation at specific CpGs within genes known to affect fibrogenesis distinguishes between patients with mild from those with severe fibrosisin both NAFLD and ALD, although same CpGs are not equally represented in both etiologies. In normal liver, age, gender or anatomical location had no significant impact on DNA methylation patterns in the liver. Conclusions: DNA methylation status at specific CpGs may be useful as part of a wider set of patient data for predicting progression to liver fibrosis., EASL Physician Scientist Sheila Sherlock Fellowship; Medical Research Council (MRC); National Institute on Alcohol Abuse and Alcoholism (NIAAA); NIHR Newcastle Biomedical Research Centre