Protective Potential of ß-Hydroxybutyrate against Glucose-Deprivation-Induced Neurotoxicity Involving the Modulation of Autophagic Flux and the Monomeric Aß Level in Neuro-2a Cells.

Hypoglycemia has been known as a potential contributory factor to neurodegenerative diseases, such as Alzheimer's disease. There may be shared pathogenic mechanisms underlying both conditions, and the ketone body, ß-hydroxybutyrate (BHB), as an alternative substrate for glucose may exert neuroprotection against hypoglycemia-induced injury. To investigate this, Neuro-2a cells were subjected to a 24 h period of glucose deprivation with or without the presence of BHB. Cell viability, reactive oxygen species (ROS) production, apoptosis, autophagy, and adenosine triphosphate (ATP) and beta-amyloid peptide (Aß) levels were evaluated. The results show that Neuro-2a cells deprived of glucose displayed a significant loss of cell survival with a corresponding decrease in ATP levels, suggesting that glucose deprivation was neurotoxic. This effect was likely attributed to the diverse mechanisms including raised ROS, defective autophagic flux and reduced basal Aß levels (particularly monomeric Aß). The presence of BHB could partially protect against the loss of cell survival induced by glucose deprivation. The mechanisms underlying the neuroprotective actions of BHB might be mediated, at least in part, through restoring ATP, and modulating ROS production, autophagy flux efficacy and the monomeric Aß level. Results imply that a possible link between the basal monomeric Aß and glucose deprivation neurotoxicity, and treatments designed for the prevention of energy impairment, such as BHB, may be beneficial for rescuing surviving cells in relation to neurodegeneration.

Quercetin Increases Mitochondrial Biogenesis and Reduces Free Radicals in Neuronal SH-SY5Y Cells.

Alzheimer's disease (AD) is a common neurodegenerative disorder that causes dementia and affects millions of people worldwide. The mechanism underlying AD is unclear; however, oxidative stress and mitochondrial biogenesis have been reported to be involved in AD progression. Previous research has also reported the reduction in mitochondrial biogenesis in the brains of patients with AD. Quercetin (QE), a type of polyphenol, has been found to be capable of increasing mitochondrial biogenesis in the body. Accordingly, we explored whether QE could reduce amyloid beta (Aß) accumulation caused by hydrogen peroxide (H2O2)-induced oxidative stress in SH-SY5Y cells. Our results revealed that QE stimulated the expression of mitochondrial-related proteins such as SIRT1, PGC-1α, and TFAM and subsequently activated mitochondrial biogenesis. Additionally, QE increased ADAM10 expression but reduced H2O2-induced reactive oxygen species production, apoptosis, ß-site amyloid precursor protein cleaving enzyme 1 expression, and Aß accumulation in the SH-SY5Y cells. These findings indicate that QE can effectively elevate mitochondrial biogenesis-related proteins and reduce the damage caused by oxidative stress, making it a promising option for protecting neuronal cells.

Protective Effects of Fucoxanthin on Hydrogen Peroxide-Induced Calcification of Heart Valve Interstitial Cells.

Cardiovascular diseases such as atherosclerosis and aortic valve sclerosis involve inflammatory reactions triggered by various stimuli, causing increased oxidative stress. This increased oxidative stress causes damage to the heart cells, with subsequent cell apoptosis or calcification. Currently, heart valve damage or heart valve diseases are treated by drugs or surgery. Natural antioxidant products are being investigated in related research, such as fucoxanthin (Fx), which is a marine carotenoid extracted from seaweed, with strong antioxidant, anti-inflammatory, and anti-tumor properties. This study aimed to explore the protective effect of Fx on heart valves under high oxidative stress, as well as the underlying mechanism of action. Rat heart valve interstitial cells under H2O2-induced oxidative stress were treated with Fx. Fx improved cell survival and reduced oxidative stress-induced DNA damage, which was assessed by cell viability analysis and staining with propidium iodide. Alizarin Red-S analysis indicated that Fx has a protective effect against calcification. Furthermore, Western blotting revealed that Fx abrogates oxidative stress-induced apoptosis via reducing the expression of apoptosis-related proteins as well as modulate Akt/ERK-related protein expression. Notably, in vivo experiments using 26 dogs treated with 60 mg/kg of Fx in combination with medical treatment for 0.5 to 2 years showed significant recovery in their echocardiographic parameters. Collectively, these in vitro and in vivo results highlight the potential of Fx to protect heart valve cells from high oxidative stress-induced damage.

A noteworthy treatment of metastatic small-cell lung cancer with afatinib, followed by subsequent development of rare metastatic lesions in the ascending and sigmoid colon.

BACKGROUND: Small-cell lung cancer (SCLC) represents a group of highly fatal diseases with a tendency toward fast growth, early metastasis, and easy development of chemotherapy resistance. In the past 30 years, few advances have been made in the systemic treatment of SCLC, and cisplatin/etoposide has remained the standard of care for limited-stage SCLC and, in combination with radiotherapy, extensive-stage SCLC. The preferred metastatic sites of SCLC include the brain, liver, adrenal glands, bone, and bone marrow. However, bowel metastasis caused by SCLC is extremely rarely proved in patients while they are still alive (although autopsy studies suggest that silent metastases to the bowel are more common), and the standard treatment for bowel metastasis has never been reported. The mean time between the identification of gastrointestinal metastasis and mortality in patients with lung cancer is 100.6 days, with a range of 21-145 days. CASE: We report the case of a patient with extensive SCLC (including brain metastasis), in which exon 19 deletion of epidermal growth factor receptor (EGFR) was detected. She initially refused chemotherapy and cranial radiotherapy and instead only agreed to oral target therapy. The second-generation EGFR-tyrosine kinase inhibitor (TKI), afatinib, was administered to the patient, and partial remission, including smaller metastatic brain tumors, was noted. Even though the subsequent development of rare metastatic lesions in the ascending and sigmoid colon was proved by colonoscopic biopsies, the prolonged overall survival (400 days) without standard treatment was marked in this case. CONCLUSION: The patient with extensive metastasis of SCLC did not receive standard systemic chemotherapy. Instead, she initially received second-generation EGFR-TKI afatinib alone and later on whole brain radiotherapy as well (3 weeks before she expired). The prolonged overall survival of 400 days was marked and is worthy of sharing and further investigation.

1,25(OH)2D3 Alleviates Aß(25-35)-Induced Tau Hyperphosphorylation, Excessive Reactive Oxygen Species, and Apoptosis Through Interplay with Glial Cell Line-Derived Neurotrophic Factor Signaling in SH-SY5Y Cells.

Amyloid beta (Aß) accumulation in the brain is one of the major pathological features of Alzheimer's disease. The active form of vitamin D (1,25(OH)2D3), which acts via its nuclear hormone receptor, vitamin D receptor (VDR), has been implicated in the treatment of Aß pathology, and is thus considered as a neuroprotective agent. However, its underlying molecular mechanisms of action are not yet fully understood. Here, we aim to investigate whether the molecular mechanisms of 1,25(OH)2D3 in ameliorating Aß toxicity involve an interplay of glial cell line-derived neurotrophic factor (GDNF)-signaling in SH-SY5Y cells. Cells were treated with Aß(25-35) as the source of toxicity, followed by the addition of 1,25(OH)2D3 with or without the GDNF inhibitor, heparinase III. The results show that 1,25(OH)2D3 modulated Aß-induced reactive oxygen species, apoptosis, and tau protein hyperphosphorylation in SH-SY5Y cells. Additionally, 1,25(OH)2D3 restored the decreasing GDNF and the inhibited phosphorylation of the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3ß (GSK-3ß) protein expressions. In the presence of heparinase III, these damaging effects evoked by Aß were not abolished by 1,25(OH)2D3. It appears 1,25(OH)2D3 is beneficial for the alleviation of Aß neurotoxicity, and it might elicit its neuroprotection against Aß neurotoxicity through an interplay with GDNF-signaling.

The mediating effect of dietary patterns on the association between mother's education level and the physical aggression of five-year-old children: a population-based cohort study.

BACKGROUND: Relatively few studies have investigated the effects of diet on behavior problems among preschoolers, particularly, physical aggression. In addition, children raised by poorly educated mothers usually have a higher probability of developing negative outcomes. Additionally, highly educated mothers have a higher probability of providing more healthy foods for their children. Thus, mothers providing healthy foods might mitigate children's behavior problems. The study aims to examine whether preschoolers' dietary pattern, as a manipulable factor, mediates the association between maternal education level and physical aggression. METHODS: Data came from the Taiwan Birth Cohort Study (TBCS), a nationally representative population-based cohort study, which included 18,513 five-year-old Taiwanese children. Mothers and primary caregivers reported the information on preschoolers' physical aggression and food consumption at age 5 and maternal education level at age 6 months. Two dietary patterns, namely a healthy diet and a high-fat-sugar-salt (HFSS) diet, were retrieved by exploratory factor analysis. Mediation hypotheses were tested by a series of multiple regression models conducted using the PROCESS macro of SAS 9.4. All models were adjusted for children's sex, parental marital status, household income, mental distress at age 5 and children's physical aggression at age 3. RESULTS: Maternal education positively linked to healthy dietary patterns (B = 0.014, p = 0.002) which was negatively associated with preschoolers' physical aggression (B = -0.096, p = 0.013), and it is negatively related to the HFSS dietary pattern (B = -0.042, p = 0.002) which was directly positively associated with preschoolers' physical aggression (B = 0.123, p = 0.008). The association between maternal education and preschoolers' physical aggression was partially mediated by preschoolers' healthy (B = -0.001, p < .001) and HFSS (B = -0.005, p = <.001) dietary patterns, respectively. The R-square of the mediation model is 0.178. CONCLUSIONS: Preschoolers' dietary patterns directly associate with their physical aggression. In addition, mothers with poor education may provide less healthy foods and more unhealthy foods to their children, which may increase the level of physical aggression. The results imply partial mediating effects of dietary patterns between maternal education and physical aggression. It is suggested that a parent-based nutritional education program focusing on healthy meal preparation for poor educated mothers might be beneficial for preschoolers' healthy development.

Equol Pretreatment Protection of SH-SY5Y Cells against Aß (25-35)-Induced Cytotoxicity and Cell-Cycle Reentry via Sustaining Estrogen Receptor Alpha Expression.

ß-amyloid formation in the brain is one of the characteristics of Alzheimer's disease. Exposure to this peptide may result in reentry into the cell cycle leading to cell death. The phytoestrogen equol has similar biological effects as estrogen without the side effects. This study investigated the possible mechanism of the neuron cell-protecting effect of equol during treatment with Aß. SH-SY5Y neuroblastoma cells were treated with either 1 µM S-equol or 10 nM 17ß-estradiol for 24 h prior to 1 µM Aß (25-35) exposure. After 24 h exposure to Aß (25-35), a significant reduction in cell survival and a reentry into the cell cycle process accompanied by increased levels of cyclin D1 were observed. The expressions of estrogen receptor alpha (ERα) and its coactivator, steroid receptor coactivator-1 (SRC-1), were also significantly downregulated by Aß (25-35) in parallel with activated extracellular signal-regulated kinase (ERK)1/2. However, pretreatment of cells with S-equol or 17ß-estradiol reversed these effects. Treatment with the ER antagonist, ICI-182,780 (1 µM), completely blocked the effects of S-equol and 17ß-estradiol on cell viability, ERα, and ERK1/2 after Aß (25-35) exposure. These data suggest that S-equol possesses a neuroprotective potential as it effectively antagonizes Aß (25-35)-induced cell cytotoxicity and prevents cell cycle reentry in SH-SY5Y cells. The mechanism underlying S-equol neuroprotection might involve ERα-mediated pathways.

A High-Fructose-High-Coconut Oil Diet Induces Dysregulating Expressions of Hippocampal Leptin and Stearoyl-CoA Desaturase, and Spatial Memory Deficits in Rats.

We investigated the effects of high-fructose-high-fat diets with different fat compositions on metabolic parameters, hippocampal-dependent cognitive function, and brain leptin (as well as stearoyl-CoA desaturase (SCD1) mRNA expressions). Thirty-two male Wistar rats were divided into 3 groups, a control group (n = 8), a high-fructose soybean oil group (37.5% of fat calories, n = 12), and a high-fructose coconut oil group (37.5% of fat calories, n = 12) for 20 weeks. By the end of the study, the coconut oil group exhibited significantly higher serum fasting glucose, fructosamine, insulin, leptin, and triglyceride levels compared to those of the control and soybean oil groups. However, hippocampal leptin expression and leptin receptor mRNA levels were significantly lower, while SCD1 mRNA was significantly higher in rats fed the high-fructose-high-coconut oil diet than in rats fed the other experimental diets. In addition, the coconut oil group spent significantly less time in the target quadrant on the probe test in the Morris water maze (MWM) task. Rats fed the high-fructose-high-coconut oil diet for 20 weeks were prone to develop hyperglycemia, hyperinsulinemia, hyperleptinemia, and hypertriglyceridemia. These metabolic consequences may contribute to hippocampal-dependent memory impairment, accompanied by a lower central leptin level, and a higher SCD1 gene expression in the brain.

Grape powder consumption affects the expression of neurodegeneration-related brain proteins in rats chronically fed a high-fructose-high-fat diet.

Abnormal glucose metabolism in the brain is recognized to be associated with cognitive decline. Because grapes are rich in polyphenols that produce antioxidative and blood sugar-lowering effects, we investigated how grape consumption affects the expression and/or phosphorylation of neurodegeneration-related brain proteins in aged rats fed a high-fructose-high-fat (HFHF) diet. Wistar rats were maintained on the HFHF diet from the age of 8 weeks to 66 weeks, and then on an HFHF diet containing either 3% or 6% grape powder as an intervention for 12 weeks. Western blotting was performed to measure the expression/phosphorylation levels of several cortical and hippocampal proteins, including amyloid precursor protein (APP), tau, phosphatidylinositol-3-kinase (PI3K), extracellular signal-regulated kinase (ERK), receptor for advanced glycation end products (RAGEs), erythroid 2-related factor 2 (Nrf2) and brain-derived neurotrophic factor (BDNF). Inclusion of up to 6% grape powder in the diet markedly reduced RAGE expression and tau hyperphosphorylation, but upregulated the expression of Nrf2 and BDNF, as well as the phosphorylation of PI3K and ERK, in the brain tissues of aged rats fed the HFHF diet. Thus, grape powder consumption produced beneficial effects in HFHF-diet-fed rats, exhibiting the potential to ameliorate changes in neurodegeneration-related proteins in the brain.

A diet containing grape powder ameliorates the cognitive decline in aged rats with a long-term high-fructose-high-fat dietary pattern.

Research has suggested that the consumption of foods rich in polyphenols is beneficial to the cognitive functions of the elderly. We investigated the effects of grape consumption on spatial learning, memory performance and neurodegeneration-related protein expression in aged rats fed a high-fructose-high-fat (HFHF) diet. Six-week-old Wistar rats were fed an HFHF diet to 66 weeks of age to establish a model of an HFHF dietary pattern, before receiving intervention diets containing different amounts of grape powder for another 12 weeks in the second part of the experiment. Spatial learning, memory performance and cortical and hippocampal protein expression levels were assessed. After consuming the HFHF diet for a year, results showed that the rats fed a high grape powder-containing diet had significantly better spatial learning and memory performance, lower expression of ß-amyloid and ß-secretase and higher expression of α-secretase than the rats fed a low grape powder-containing diet. Therefore, long-term consumption of an HFHF diet caused a decline in cognitive functions and increased the risk factors for neurodegeneration, which could subsequently be ameliorated by the consumption of a polyphenol-rich diet.

Cholesterol overload induces apoptosis in SH-SY5Y human neuroblastoma cells through the up regulation of flotillin-2 in the lipid raft and the activation of BDNF/Trkb signaling.

Epidemiological investigations have shown that Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. It has been indicated that the cholesterol concentration in the brain of AD patients is higher than that in normal people. In this study, we investigated the effects of cholesterol concentrations, 0, as the control, 3.125, 12.5, and 25µM, on cholesterol metabolism, neuron survival, AD-related protein expressions, and cell morphology and apoptosis using SH-SY5Y human neuroblastoma cells. We observed that expressions of cholesterol hydroxylase (Cyp46), flotillin-2 (a marker of lipid raft content), and truncated tyrosine kinase B (TrkBtc) increased, while expressions of brain-derived neurotrophic factor (BDNF) and full-length TrkB (TrkBfl) decreased as the concentration of cholesterol loading increased. Down-regulation of the PI3K-Akt-glycogen synthase kinase (GSK)-3ß cascade and cell apoptosis were also observed at higher concentrations of cholesterol, along with elevated levels of ß-amyloid (Aß), ß-secretase (BACE), and reactive oxygen species (ROS). In conclusion, we found that cholesterol overload in neuronal cells imbalanced the cholesterol homeostasis and increased the protein expressions causing cell apoptosis, which illustrates the neurodegenerative pathology of abnormally elevated cholesterol concentrations found in AD patients.

Reciprocal relationship between unhealthy eating behaviours and depressive symptoms from childhood to adolescence: 10-year follow-up of the Child and Adolescent Behaviors in Long-Term Evolution study.

OBJECTIVE: To investigate the reciprocal relationship between unhealthy eating behaviours and depressive symptoms from childhood to adolescence. DESIGN: Unhealthy eating behaviours were measured by the frequencies of eating foods with excess salt, sugar or fat in the past week. Depressive symptoms in the past two weeks were measured using a seven-item scale. Hierarchical linear growth models were used to analyse longitudinal associations between unhealthy eating behaviours and depressive symptoms. Time-fixed variables (sex, parents' education level and household monthly income) and time-varying variables (parents' marital status, family activities, body weight, vegetable or fruit consumption, exercising and smoking) were controlled for. SETTING: The Child and Adolescent Behaviors in Long-Term Evolution study, which commenced in 2001 and has annual follow-up. SUBJECTS: Students (n 2630) followed from 2nd grade (8 years old in 2002) to 11th grade. RESULTS: The frequency of unhealthy eating behaviours in the previous year and the difference between the frequency in the previous and successive year were positively associated with the initiation and growth rate of depressive symptoms. Depressive symptoms in the previous year and the difference in depressive symptoms between the previous and successive year were positively associated with the initial state and growth rate of unhealthy eating behaviours. CONCLUSIONS: Our results suggest a reciprocal relationship between depressive symptoms and unhealthy eating behaviours. This relationship should be considered when developing programmes targeting depressive symptoms and unhealthy diet in children and adolescents.

A high-cholesterol diet enriched with polyphenols from Oriental plums (Prunus salicina) improves cognitive function and lowers brain cholesterol levels and neurodegenerative-related protein expression in mice.

Ageing accompanied by a decline in cognitive performance may be a result of the long-term effects of oxidative stress on neurologic processes. It has been shown that high-cholesterol contents in the blood and brain may lead to the deposition of the ß-amyloid (Aß) protein in the brain, which damages brain cells. The present study was designed to observe the effect of polyphenol-rich Oriental plums on cognitive function and cerebral neurodegeneration-related protein expression in mice that were fed a high-cholesterol diet for 5 months. The study consisted of four groups: the control (Ctrl) group, which was fed the American Institute of Nutrition (AIN)-93M diet; the high cholesterol (HC) group, which was fed the AIN-93M diet with 5% cholesterol; the high cholesterol + low Oriental plum (LOP) group, which was fed the AIN-93M diet with 5% cholesterol and 2% Oriental plum powder; and the high cholesterol + high Oriental plum (HOP) group, which was fed the AIN-93M diet with 5% cholesterol and 5% Oriental plum powder. Measurements of cognitive function were assessed using the Morris water maze, and the mRNA expression of cholesterol hydroxylase (Cyp46), Aß and ß-secretase 1 (BACE1) were analysed. The results showed that cholesterol concentrations in both the blood and the brain were significantly higher in the HC group than in the Ctrl and HOP groups at the end of the trial. The high-cholesterol diet per se produced significant cognitive deficits, which were accompanied by a significantly increased mRNA expression of Cyp46, BACE1, Aß and 24-hydroxycholesterol in the brain cortex and hippocampus. However, all of these variables were non-significantly increased in the HOP group as compared to the Ctrl group. In conclusion, incorporating polyphenol-enriched Oriental plum into a high-cholesterol diet can ameliorate some of the symptoms of neurodegenerative conditions.

Palmitic acid-induced neuron cell cycle G2/M arrest and endoplasmic reticular stress through protein palmitoylation in SH-SY5Y human neuroblastoma cells.

Obesity-related neurodegenerative diseases are associated with elevated saturated fatty acids (SFAs) in the brain. An increase in SFAs, especially palmitic acid (PA), triggers neuron cell apoptosis, causing cognitive function to deteriorate. In the present study, we focused on the specific mechanism by which PA triggers SH-SY5Y neuron cell apoptosis. We found that PA induces significant neuron cell cycle arrest in the G2/M phase in SH-SY5Y cells. Our data further showed that G2/M arrest is involved in elevation of endoplasmic reticular (ER) stress according to an increase in p-eukaryotic translation inhibition factor 2α, an ER stress marker. Chronic exposure to PA also accelerates beta-amyloid accumulation, a pathological characteristic of Alzheimer's disease. Interestingly, SFA-induced ER stress, G2/M arrest and cell apoptosis were reversed by treatment with 2-bromopalmitate, a protein palmitoylation inhibitor. These findings suggest that protein palmitoylation plays a crucial role in SFA-induced neuron cell cycle G2/M arrest, ER stress and apoptosis; this provides a novel strategy for preventing SFA-induced neuron cell dysfunction.

Application of the solvent extraction technique to investigation of the anti-inflammatory activity of adlay bran.

The current study utilised a bioassay-directed chemical analysis scheme to screen the anti-inflammatory activity of fractions and compounds from adlay bran (AB). Liquid-liquid extraction couple with liquid chromatography-mass spectrometry (LC-MS) was applied to the isolation, analysis and identification of active components in AB samples. Ethanol extracts of AB (ABE) and ethyl acetate extracts AB (ABEa) were obtained and further partitioned with different solvents. The results showed that among all 16 kinds of fractions from ABE and ABEa, ABEa-Ea-B (80% Ea/n-hexane sub-fraction from ABE-Ea) had the most potent inhibitory effects on NO production, iNOS and COX-2 expressions, and proinflammatory IL-6 and TNF-α secretion in lipopolysaccharide-activated RAW264.7 cells system. Mechanistic data from luciferase reporter-gene assay revealed that the anti-inflammatory action of ABEa-Ea-B may be associated with inhibition of NF-kB transcriptional activity. Notably, tangeretin, nobiletin, and p-hydroxybenzoic acid were found to be the main active compounds for the anti-inflammatory properties in ABEa-Ea-B.

Identification of sinensetin metabolites in rat urine by an isotope-labeling method and ultrahigh-performance liquid chromatography-electrospray ionization mass spectrometry.

Sinensetin (SIN), one of the major polymethoxyflavones (PMFs) contained mainly in the citrus peels, has been reported to possess various bioactivities, including antifungal, antimutagenic, anticancer, and anti-inflammatory activities. Although the biotransformation of SIN in fungi and insects has been reported, the information about the metabolism of SIN in mammals is still unclear. In this study, formation of SIN metabolites in rats was investigated. Four isotope-labeled SINs ([4'-D3]SIN, [3'-D3]SIN, [5-D3]SIN, and [6-D3]SIN) were synthesized and administered to rat. The urine samples were collected and main metabolites were monitored by ultrahigh-performance liquid chromatography-electrospray ionization mass spectrometry. The administered compound and four SIN metabolites were detected in rat urine. These metabolites were identified as 4'-hydroxy-5,6,7,3'-tetramethoxyflavone, 5-hydroxy-6,7,3',4'-tetramethoxyflavone, 6-hydroxy-5,7,3',4'-tetramethoxyflavone, and 7-hydroxy-5,6,3',4'-tetramethoxyflavone sulfate.

A novel synthetic microtubule inhibitor, MPT0B214 exhibits antitumor activity in human tumor cells through mitochondria-dependent intrinsic pathway.

Agents that interfere with mitotic progression by disturbing microtubule dynamics are commonly used for cancer treatment. Previously, a series of aroylquinolone regioisomers as novel microtubule inhibitors were discovered. One of these new compounds, MPT0B214 inhibited tubulin polymerization through strongly binding to the tubulin's colchicine-binding site and had cytotoxic activity in a variety of human tumor cell lines. After treatment with MPT0B214, KB cells were arrested in the G2-M phase before cell death occurred, which were associated with upregulation of cyclin B1, dephosphorylation of Cdc2, phosphorylation of Cdc25C and elevated expression of the mitotic marker MPM-2. Furthermore, the compound induced apoptotic cell death through mitochondria/caspase 9-dependent pathway. Notably, several KB-derived multidrug-resistant cancer cell lines were also sensitive to MPT0B214 treatment. These findings showed that MPT0B214 is a potential compound in the treatment of various malignancies.

Practical management of the increasing burden of non-alcoholic fatty liver disease.

Obesity-induced liver disease (non-alcoholic fatty liver disease (NAFLD)) describes a spectrum from steatosis through steatohepatitis to cirrhosis. Its prevalence is rising in tandem with societal rates of obesity which through consequent insulin resistance and fat deposition in hepatocytes lead to hepatocyte death and attempts at repair, which if persistent, lead to activation of liver fibrogenic cells. NAFLD, which may also progress to primary liver cancer, is now the most common cause of chronic liver disease in affluent countries. There is currently no single accurate diagnostic test besides a liver biopsy. The decision to consider a liver biopsy will be informed by the presence of insulin resistance determined by comparatively easy-to-measure factors together with other putative markers of progression such as hypertension. If a liver biopsy is performed, patients with steatosis with no evidence of inflammation may be less aggressively managed while those with steatohepatitis, since they have a faster trajectory to cirrhosis, should be managed more robustly. Besides lifestyle changes and increased aerobic exercise other strategies include considering referral to centres with ongoing clinical trials. Emerging treatments include α1 adrenoceptors antagonists, angiotensin receptor blockers, glitazones and vitamin E.