Dietary broccoli impedes Western diet-enhanced fatty liver and hepatocellular carcinoma development

Liver is the metabolic center for energy homeostasis in our body, maintaining a balance between carbohydrate and fat metabolism. The “Westernized” dietary pattern, which is known for high saturated fat and refined sugar and rooted in the lifestyle of a large proportion of the world’s population, may greatly disrupt energy balance, resulting in obesity and obesity-related diseases. Non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma, which is also a possible endpoint of NAFLD, are both enhanced by adiposity and inflammation, and almost symptomless until serious damage is caused in liver. However, these diseases can be preventable, by changing lifestyle and diet. Broccoli, a well-accepted brassica vegetable in the United States, has the potential to reduce cancer risk and ameliorate inflammation. Therefore, in this study, we aimed to understand the impact of dietary broccoli on the development of NAFLD and liver cancer in mice fed a Western diet. Accordingly, we proposed a whole dietary broccoli intervention. A combined Western diet-fed and diethylnitrosamine (DEN)-treated mouse liver cancer models was used in order to evaluate the changes in hepatic lipidosis, macrophage activation, and tumorigenesis after long-term consumption of broccoli. Our results show that dietary broccoli decreased hepatic lipidosis as early as 3 months after initiation, and effectively down-regulated liver damage. The enlarged hepatic triglyceride pool due to the Western diet was narrowed by dietary broccoli, lowering the influx of non-esterified fatty acids but increasing the excretion of very-low-density lipoprotein. Activation of hepatic macrophages, was lowered by continues consumption of broccoli. Furthermore, DEN-induced liver tumor size and hepatic neoplasm-related lesion formation were both decreased by dietary broccoli. In addition, as an incidental finding, intraperitoneal DEN-induced nasal epithelial neoplasm-related lesions in B6C3F1 mice are first reported in this study. Overall, whole broccoli dietary intervention has the potential to impede the progression of NAFLD, from hepatic steatosis, through steatohepatitis, to hepatocellular carcinoma. This study fills gaps of knowledge about the impact of broccoli on hepatic lipid metabolism, supports the cancer preventive effect of brassicas revealed by epidemiologic studies, and further encourages the whole food dietary intervention. Translation to clinical studies is needed

Electroencephalography and transcranial Doppler ultrasonography in neonatal citrullinemia

The authors present a case of citrullinemia with a genotype of argininosuccinate synthetase (ASS1), c.380 G>A (p.R127Q)/c.380 G>A (p.R127Q), in two alleles. A 3-day-old female infant presented with status epilepticus and coma. Laboratory data showed hyperammonemia and marked lactic acidosis in the blood and cerebrospinal fluid; electroencephalography showed severely suppressed cerebral activity and focal paroxysmal volleys of slow and sharp waves (< 1Hz) over the left hemisphere. Real-time transcranial Doppler ultrasonography showed a brain edema and high peaked systolic and low diastolic flows in basal, anterior, and middle cerebral arteries; however, immediately after a blood exchange transfusion, systolic flows were lower and diastolic flows were higher. The resistance indices were significantly different (means: 0.58 vs. 0.37; p=0.01). The patient was placed on diet therapy. After six blood exchange transfusions and peritoneal dialysis, her neurologic examination results and serum ammonia and lactate values were normal. The authors found that electroencephalography and transcranial Doppler ultrasonography were useful for the diagnosis and follow-up treatment of neonatal citrullinemia

Reinfusion of ascites during hemodialysis as a treatment of massive refractory ascites and acute renal failure

Refractory ascites can occur in patients with various conditions. Although several procedures based on the reinfusion of ascitic fluid have been reported after the failure of bed rest, salt and water restriction, diuretics, intravenous administration of albumin, and repeated paracentesis, these procedures are performed for ascitic fluid removal without dialytic effect. In this study, a flow control reinfusion of ascites during hemodialysis (HD) was performed to demonstrate the efficacy of this method in a lupus patient with massive refractory ascites and respiratory and acute renal failure (ARF). The alleviation of ascites and ARF attests to the success of the flow control reinfusion of ascites during HD. This procedure can control the rate of ascites and body fluid removal simultaneously during HD using the roller pump. In conclusion, with a normal coagulation profile, the procedure of flow control reinfusion of ascites during HD is an effective alternative treatment for the alleviation of refractory ascites with renal failure

Continuous Production of Lipase-Catalyzed Biodiesel in a Packed-Bed Reactor: Optimization and Enzyme Reuse Study

An optimal continuous production of biodiesel by methanolysis of soybean oil in a packed-bed reactor was developed using immobilized lipase (Novozym 435) as a catalyst in a tert-butanol solvent system. Response surface methodology (RSM) and Box-Behnken design were employed to evaluate the effects of reaction temperature, flow rate, and substrate molar ratio on the molar conversion of biodiesel. The results showed that flow rate and temperature have significant effects on the percentage of molar conversion. On the basis of ridge max analysis, the optimum conditions were as follows: flow rate 0.1 mL/min, temperature 52.1°C, and substrate molar ratio 1 : 4. The predicted and experimental values of molar conversion were 83.31 ± 2.07% and 82.81 ± .98%, respectively. Furthermore, the continuous process over 30 days showed no appreciable decrease in the molar conversion. The paper demonstrates the applicability of using immobilized lipase and a packed-bed reactor for continuous biodiesel synthesis

Inhibition of Mitochondria- and Endoplasmic Reticulum Stress-Mediated Autophagy Augments Temozolomide-Induced Apoptosis in Glioma Cells

Autophagy is a crucial process for cells to maintain homeostasis and survival through degradation of cellular proteins and organelles, including mitochondria and endoplasmic reticula (ER). We previously demonstrated that temozolomide (TMZ), an alkylating agent for brain tumor chemotherapy, induced reactive oxygen species (ROS)/extracellular signal-regulated kinase (ERK)-mediated autophagy to protect glioma cells from apoptosis. In this study, we investigated the role of mitochondrial damage and ER stress in TMZ-induced cytotoxicity. Mitochondrial depolarization and mitochondrial permeability transition pore (MPTP) opening were observed as a prelude to TMZ-induced autophagy, and these were followed by the loss of mitochondrial mass. Electron transport chain (ETC) inhibitors, such as rotenone (a complex I inhibitor), sodium azide (a complex IV inhibitor), and oligomycin (a complex V inhibitor), or the MPTP inhibitor, cyclosporine A, decreased mitochondrial damage-mediated autophagy, and therefore increased TMZ-induced apoptosis. TMZ treatment triggered ER stress with increased expression of GADD153 and GRP78 proteins, and deceased pro-caspase 12 protein. ER stress consequently induced autophagy through c-Jun N-terminal kinases (JNK) and Ca2+ signaling pathways. Combination of TMZ with 4-phenylbutyrate (4-PBA), an ER stress inhibitor, augmented TMZ-induced cytotoxicity by inhibiting autophagy. Taken together, our data indicate that TMZ induced autophagy through mitochondrial damage- and ER stress-dependent mechanisms to protect glioma cells. This study provides evidence that agents targeting mitochondria or ER may be potential anticancer strategies