This review is directed at understanding how neuronal death occurs in two distinct insults, global ischemia and focal ischemia. These are the two principal rodent models for human disease. Cell dea...

Ischemic Cell Death in Brain Neurons

Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and represents a growing challenge in terms of prevention and treatment. Despite its high prevalence, only a small minority of affected patients develops inflammation and subsequently fibrosis and chronic liver disease, while most of them only exhibit simple steatosis. In this context, the full understanding of the mechanisms underlying the development of NAFLD and non-alcoholic steatohepatitis (NASH) is of extreme importance; despite advances in this field, knowledge on the pathogenesis of NAFLD is still incomplete. The 'two-hit' hypothesis is now obsolete, as it is inadequate to explain the several molecular and metabolic changes that take place in NAFLD. The "multiple hit" hypothesis considers multiple insults acting together on genetically predisposed subjects to induce NAFLD and provides a more accurate explanation of NAFLD pathogenesis. Such hits include insulin resistance, hormones secreted from the adipose tissue, nutritional factors, gut microbiota and genetic and epigenetic factors. In this article, we review the factors that form this hypothesis.

/pdf/the-multiple-hit-pathogenesis-of-non-alcoholic-fatty-liver-4b2gfxdwuu.pdf

The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)

Consumption of fruits and vegetables, particularly green leafy vegetables and vitamin C–rich fruits and vegetables, appears to have a protective effect against coronary heart disease.

/pdf/the-effect-of-fruit-and-vegetable-intake-on-risk-for-2gb5zy11tb.pdf

The Effect of Fruit and Vegetable Intake on Risk for Coronary Heart Disease

During the last few years, research on toxicologically relevant properties of engineered nanoparticles has increased tremendously. A number of international research projects and additional activities are ongoing in the EU and the US, nourishing the expectation that more relevant technical and toxicological data will be published. Their widespread use allows for potential exposure to engineered nanoparticles during the whole lifecycle of a variety of products. When looking at possible exposure routes for manufactured Nanoparticles, inhalation, dermal and oral exposure are the most obvious, depending on the type of product in which Nanoparticles are used. This review shows that (1) Nanoparticles can deposit in the respiratory tract after inhalation. For a number of nanoparticles, oxidative stress-related inflammatory reactions have been observed. Tumour-related effects have only been observed in rats, and might be related to overload conditions. There are also a few reports that indicate uptake of nanoparticles in the brain via the olfactory epithelium. Nanoparticle translocation into the systemic circulation may occur after inhalation but conflicting evidence is present on the extent of translocation. These findings urge the need for additional studies to further elucidate these findings and to characterize the physiological impact. (2) There is currently little evidence from skin penetration studies that dermal applications of metal oxide nanoparticles used in sunscreens lead to systemic exposure. However, the question has been raised whether the usual testing with healthy, intact skin will be sufficient. (3) Uptake of nanoparticles in the gastrointestinal tract after oral uptake is a known phenomenon, of which use is intentionally made in the design of food and pharmacological components. Finally, this review indicates that only few specific nanoparticles have been investigated in a limited number of test systems and extrapolation of this data to other materials is not possible. Air pollution studies have generated indirect evidence for the role of combustion derived nanoparticles (CDNP) in driving adverse health effects in susceptible groups. Experimental studies with some bulk nanoparticles (carbon black, titanium dioxide, iron oxides) that have been used for decades suggest various adverse effects. However, engineered nanomaterials with new chemical and physical properties are being produced constantly and the toxicity of these is unknown. Therefore, despite the existing database on nanoparticles, no blanket statements about human toxicity can be given at this time. In addition, limited ecotoxicological data for nanomaterials precludes a systematic assessment of the impact of Nanoparticles on ecosystems.

/pdf/the-potential-risks-of-nanomaterials-a-review-carried-out-t45f9crq14.pdf

The potential risks of nanomaterials: a review carried out for ECETOC

https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.26093

Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: A connection between endogenous alcohol and NASH

Breath analysis is a young field of research with its roots in antiquity. Antoine Lavoisier discovered carbon dioxide in exhaled breath during the period 1777-1783, Wilhelm (Vilem) Petters discovered acetone in breath in 1857 and Johannes Muller reported the first quantitative measurements of acetone in 1898. A recent review reported 1765 volatile compounds appearing in exhaled breath, skin emanations, urine, saliva, human breast milk, blood and feces. For a large number of compounds, real-time analysis of exhaled breath or skin emanations has been performed, e.g., during exertion of effort on a stationary bicycle or during sleep. Volatile compounds in exhaled breath, which record historical exposure, are called the 'exposome'. Changes in biogenic volatile organic compound concentrations can be used to mirror metabolic or (patho)physiological processes in the whole body or blood concentrations of drugs (e.g. propofol) in clinical settings-even during artificial ventilation or during surgery. Also compounds released by bacterial strains like Pseudomonas aeruginosa or Streptococcus pneumonia could be very interesting. Methyl methacrylate (CAS 80-62-6), for example, was observed in the headspace of Streptococcus pneumonia in concentrations up to 1420 ppb. Fecal volatiles have been implicated in differentiating certain infectious bowel diseases such as Clostridium difficile, Campylobacter, Salmonella and Cholera. They have also been used to differentiate other non-infectious conditions such as irritable bowel syndrome and inflammatory bowel disease. In addition, alterations in urine volatiles have been used to detect urinary tract infections, bladder, prostate and other cancers. Peroxidation of lipids and other biomolecules by reactive oxygen species produce volatile compounds like ethane and 1-pentane. Noninvasive detection and therapeutic monitoring of oxidative stress would be highly desirable in autoimmunological, neurological, inflammatory diseases and cancer, but also during surgery and in intensive care units. The investigation of cell cultures opens up new possibilities for elucidation of the biochemical background of volatile compounds. In future studies, combined investigations of a particular compound with regard to human matrices such as breath, urine, saliva and cell culture investigations will lead to novel scientific progress in the field.

https://iopscience.iop.org/article/10.1088/1752-7155/8/3/034001/pdf

The human volatilome: volatile organic compounds (VOCs) in exhaled breath, skin emanations, urine, feces and saliva

Clinical breath analysis remains in its infancy, despite the fact that its potential has been recognized for centuries and that blood, urine, and other bodily fluids and tissues are routinely analyzed to diagnose disease or to monitor therapy. This review discusses the present status of clinical breath analysis and suggests reasons why breath analysis has not received similar widespread clinical use. Currently, a number of marker molecules have been identified in breath that could be used to identify disease, disease progression, or to monitor therapeutic intervention and this list is expected increase dramatically since the analysis of breath is ideally suited for population-based studies in the developed and underdeveloped world. Recent advances in analytical instrumentation have suggested that the use of exhaled breath in medicine should now be re-examined. In particular, the availability of real-time, portable monitors will represent a breakthrough for clinical diagnosis. Progress in clinical breath analysis will require collaboration amongst device makers, experts in breath analysis, and clinicians.

Current status of clinical breath analysis

https://www.gastrojournal.org/article/S0016-5085(00)20235-7/pdf

Increased gastrointestinal ethanol production in obese mice: Implications for fatty liver disease pathogenesis

Clinical application of breath biomarkers of oxidative stress status.

Background—Free radical–mediated oxidative damage to lipids is thought to be an important process in the pathogenesis of atherosclerosis. Although previous studies have demonstrated a beneficial impact of antioxidant vitamin supplements on lipid peroxidation, the effect of dietary patterns on lipid peroxidation is unknown. Methods and Results—During the 3-week run-in period of a randomized trial, 123 healthy individuals were fed a control diet, low in fruits, vegetables, and dairy products, with 37% of calories from fat. Participants were then randomized to consume for 8 weeks: (1) the control diet, (2) a diet rich in fruits and vegetables but otherwise similar to the control diet, and (3) a combination diet rich in fruits, vegetables, and low-fat dairy products and reduced in fat. Serum oxygen radical–absorbing capacity, malondialdehyde (an in vitro measure of lipid peroxidation), and breath ethane (an in vivo measure of lipid peroxidation) were measured at the end of run-in and intervention periods. Bet...

Terence H. Risby

Papers

The human volatilome: volatile organic compounds (VOCs) in exhaled breath, skin emanations, urine, feces and saliva

Current status of clinical breath analysis

Increased gastrointestinal ethanol production in obese mice: Implications for fatty liver disease pathogenesis

Clinical application of breath biomarkers of oxidative stress status.

Effect of dietary patterns on measures of lipid peroxidation: results from a randomized clinical trial.