Diverse Polycyclic Polyprenylated Acylphloroglucinol Congeners with Anti-Nonalcoholic Steatohepatitis Activity from Hypericum forrestii.

The new polycyclic polyprenylated acylphloroglucinols, hyperforcinols A-J (1-10), were isolated from the fruits of Hypericum forrestii, together with 30 biogenetic congeners of known structures. The structures of hyperforcinols A-J were determined by HRESIMS and 1D/2D NMR spectroscopic analysis, and their absolute configurations were determined by a combination of the electronic circular dichroism (ECD) exciton chirality method, ECD calculations, and X-ray diffraction analysis. A selection of 25 isolates, possessing seven types of carbon skeletons, were assessed for their in vitro effects against nonalcoholic steatohepatitis (NASH) using a free fatty acid-induced L02 cell model. Compounds 20 and 40 significantly decreased intracellular lipid accumulation. QRT-PCR analyses revealed that compounds 20 and 40 regulate the expression of lipid metabolism-related genes, including CD36, FASN, PPARα, and ACOX1.

Diagnosis of non-alcoholic fatty liver disease (NAFLD).

Non-alcoholic fatty liver disease (NAFLD) increases risk of mortality from liver and cardiovascular disease (CVD) and is the major cause of hepatocellular carcinoma (HCC), which may develop without cirrhosis. NAFLD predicts type 2 diabetes, even independently of obesity. Globally, the prevalence of NAFLD averages 25% and is as common as the metabolic syndrome. The majority of patients with type 2 diabetes have NAFLD. The challenge for the diabetologist is to identify patients at risk of advanced liver disease and HCC. At a minimum, liver function tests (LFTs), despite being neither specific nor sensitive, should be performed in all patients with the metabolic syndrome or type 2 diabetes. Increases in LFTs, for which the updated reference values are lower (serum ALT ≈30 U/l in men and ≈20 U/l in women) than those hitherto used in many laboratories, should prompt assessment of fibrosis biomarkers and referral of individuals at risk to a NAFLD/hepatology clinic. Preferably, evaluation of NAFLD should be based on measurement of steatosis biomarkers or ultrasound if easily available. A large number of individuals carry the patatin-like phospholipase domain containing 3 (PNPLA3) I148M variant (30-50%) or the transmembrane 6 superfamily member 2 (TM6SF2) E167K variant (11-15%). These variants increase the risk of advanced liver disease and HCC but not of diabetes or CVD. Genotyping of selected patients for these variants is recommended. Many patients have 'double trouble', i.e. carry both a genetic risk factor and have the metabolic syndrome. Excess use of alcohol could be a cause of 'triple trouble', but such patients would be classified as having alcoholic fatty liver disease. This review summarises a presentation given at the symposium 'The liver in focus' at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Kenneth Cusi, DOI: 10.1007/s00125-016-3952-1 , and by John Jones, DOI: 10.1007/s00125-016-3940-5 ) and a commentary by the Session Chair, Michael Roden (DOI: 10.1007/s00125-016-3911-x ).

John Nash, game theory, and the schizophrenic brain.

This article focuses on John Nash, recipient of the Nobel Prize in Economics in 1994, and subject of the Award winning 2001 film A Beautiful Mind, who was diagnosed with paranoid schizophrenia in 1958 at the age of 29. After presenting an account of the emergence, course, and eventual remission of his illness, the article argues for the relevance of his contribution to game theory, known as the Nash equilibrium, for which he received the Nobel Prize, to research studies of the schizophrenic brain and how it deviates from the normal brain. The case is made that the Nash equilibrium is descriptive of the normal brain, whereas the game theory formulated by John van Neumann, which Nash's theory challenges, is descriptive of the schizophrenic brain. The fact that Nash and his colleagues in mathematics did not make the association between his contributions to mathematics and his mental breakdown and that his later recovery exemplified the validity of this contribution are noted and discussed. Religious themes in his delusional system, including his view of himself as a secret messianic figure and the biblical Esau, are interpreted in light of these competing game theories and the dysfunctions of the schizophrenic brain. His recognition that his return to normalcy came at the price of his sense of being in relation to the cosmos is also noted.

Nash: genius with schizophrenia or vice versa?

Schizophrenia has many negative impacts on the wellbeing of individuals (sufferers). I will critically analyse Nash's experience with his illness of schizophrenia and his concept of wellness based on themes, his journey with schizophrenia and the support of this wife and friends. Ron Howard directed the movie, A Beautiful Mind based on Nash's biography about his mathematical genius and his struggle with schizophrenia. Nash only had one sister, Martha Nash who was born on November 16th, 1930. In terms of his mental health and wellness, Nash began to show signs of schizophrenia in 1958, on the threshold of his career. After 1970, by his choice, he never took antipsychotic medication again. In 1978, Nash was awarded the John von Neumann Theory Prize for his discovery of non-cooperative equilibria, now called Nash equilibria. As a result of Nash's illness, he adopted unhealthy practices that did not help him cope with schizophrenia. Recovery from mental illness has emphasised the importance of hope for the people experiencing mental illness. Nash's self-determinations enabled him to overcome the stigmatisation suffering due to schizophrenia. Nash experienced the five stages of coping with mental illness. The support of Nash's wife Alicia and the few close friends he had were paramount to his recovery and living with schizophrenia. Alicia had used cognitive coping strategies with her caring for Nash by having positive thinking in attempting to accept Nash's illness rather than denying that it existed and to understand the life experiences of a person with schizophrenia. Howard (2001) stated that it's about a 25% chance, that survivors of schizophrenia can regain clarity as Nash did within a certain time period.