Natural Compounds for Counteracting Nonalcoholic Fatty Liver Disease (NAFLD): Advantages and Limitations of the Suggested Candidates

The booming prevalence of nonalcoholic fatty liver disease (NAFLD) in adults and children will threaten the health system in the upcoming years. The “multiple hit” hypothesis is the currently accepted explanation of the complex etiology and pathophysiology of the disease. Some of the critical pathological events associated with the development of NAFLD are insulin resistance, steatosis, oxidative stress, inflammation, and fibrosis. Hence, attenuating these events may help prevent or delay the progression of NAFLD. Despite an increasing understanding of the mechanisms involved in NAFLD, no approved standard pharmacological treatment is available. The only currently recommended alternative relies on lifestyle modifications, including diet and physical activity. However, the lack of compliance is still hampering this approach. Thus, there is an evident need to characterize new therapeutic alternatives. Studies of food bioactive compounds became an attractive approach to overcome the reticence toward lifestyle changes. The present study aimed to review some of the reported compounds with beneficial properties in NAFLD; namely, coffee (and its components), tormentic acid, verbascoside, and silymarin. We provide details about their protective effects, their mechanism of action in ameliorating the critical pathological events involved in NAFLD, and their clinical applications.     

Linear and Cyclic Depsipeptidomimetics with β‐Lactam Cores: A Class of New αvβ3 Integrin Receptor Inhibitors

The α_vβ₃ integrin receptor plays an important role in tumor metastasis and tumor‐induced angiogenesis. The inhibition of this receptor with diverse ligands, antibodies, or cyclic peptides is a promising research field for the treatment of a variety of tumors. The replacement of Phe‐(Me)Val dipeptide by a β‐lactam ring in Cilengitide has led to new products that show higher inhibitory activity than the parent cyclopeptide. In particular, substitution of a peptide bond β‐lactam‐NH‐Asp linkage by a β‐lactam‐O‐Asp ester linkage increases the activity of the new cyclodepsipeptide. In the same way it has been found that open‐chain compounds of the form Asp‐β‐lactam‐Arg can interact with the receptor and inhibit its activity moderately. The integrin inhibitory activity of the synthesized compounds has been established by using the CGH array, a method that appears to be a more reliable trial than the classical adhesion test.     

Direct and Enantioselective Vinylogous Michael Addition of α‐Alkylidenepyrazolinones to Nitroolefins Catalyzed by Dual Cinchona Alkaloid Thioureas

While several protocols exist for the asymmetric functionalization of pyrazolinones at the α‐position relying on nucleophilic addition or annulation procedures, use of α‐alkylidene electron‐rich analogues in asymmetric vinylogous coupling to carbon electrophiles is substantially an uncharted domain. We now report, for the first time, that alkylidenepyrazolinones carrying an enolizable carbon at the γ‐position efficiently participate in direct and asymmetric, catalytic vinylogous Michael‐type additions to nitroolefins providing the expected adducts in high yields, with complete γ‐site selectivity and with extraordinary levels of enantio‐, diastereo‐, and geometrical selectivities. Both enantiomeric adducts were equally accessed by employing a quasi‐enantiomeric quinine‐ or quinidine‐based thiourea catalyst pair.

     

Effect of brominated vegetable oils on heart lipid metabolism

Normal rats fed for 105 days on an experimental diet made up of standard laboratory chow supplemented with 0.5% of a mixture of brominated sunflower-olive oil (BVO) developed a significant increase in the triacylglycerol content of the heart, liver and soleus muscle compared to controls. In addition, BVO-treated rats had a decrease in plasma levels of triacylglycerol and total and HDL cholesterol. Plasma fatty acid levels and plasma post-heparin lipolytic activities, such as H-TGL, LPL, T-TGL and MGH were similar to those of control animals fed the standard chow alone. Heart PDH_a (active portion of pyruvate dehydrogenase) was dramatically decreased in the BVO-fed rats. A faster rate of spontaneous lipolysis was recorded in the isolated perfused preparation of hearts from the experimental animals. The addition of 10⁻⁷ M of glucagon to the perfusate, however, revealed a lipolytic effect comparable to the one observed in the control rats. In summary, our findings of normal fatty acids and low triacylglycerol plasma levels associated with normal activities of the various PHLA (post-heparin lipolytic activity) enzymes suggest that accumulation of triacylglycerol in heart muscle may not be explained essentially in terms of an elevated uptake and/or increased delivery of plasma fatty acids or plasma triacylglycerol. A decreased in situ catabolism of tissue triacylglycerol also appears unlikely because the spontaneous as well as the glucagon induced lipolysis in the heart both were found to be unimpaired. Our results suggest that the mechanisms involved in the toxicologic effects of a BVO diet on heart lipid metabolism could be exerted mainly at the level of triacylglycerol biosynthesis rather than a derangement in some known step of their catabolic pathway. Additional studies are necessary to clarify this matter. An abstract pertaining to this work was presented in November 1984 at the IV Congress of the Pan American Association of Biochemical Societies (PAABS), Buenos Aires, Argentina.     

Heat recovery from Diesel engines: A thermodynamic comparison between Kalina and ORC cycles

In the context of heat recovery for electric power generation, Kalina cycle (a thermodynamic cycle using as working fluid a mixture of water and ammonia) and Organic Rankine Cycle (ORC) represent two different eligible technologies. In this work a comparison between the thermodynamic performances of Kalina cycle and an ORC cycle, using hexamethyldisiloxane as working fluid, was conducted for the case of heat recovery from two Diesel engines, each one with an electrical power of 8900 kWe. The maximum net electric power that can be produced exploiting the heat source constituted by the exhaust gases mass flow (35 kg/s for both engines, at 346 °C) was calculated for the two thermodynamic cycles. Owing to the relatively low useful power, for the Kalina cycle a relatively simple plant layout was assumed. Supposing reasonable design parameters and a logarithmic mean temperature difference in the heat recovery exchanger of 50 °C, a net electric power of 1615 kW and of 1603 kW respectively for the Kalina and for the ORC cycle was calculated.Although the obtained useful powers are actually equal in value, the Kalina cycle requires a very high maximum pressure in order to obtain high thermodynamic performances (in our case, 100 bar against about 10 bar for the ORC cycle). So, the adoption of Kalina cycle, at least for low power level and medium–high temperature thermal sources, seems not to be justified because the gain in performance with respect to a properly optimized ORC is very small and must be obtained with a complicated plant scheme, large surface heat exchangers and particular high pressure resistant and no-corrosion materials.     

In-situ neutron diffraction study of magnesium amide/lithium hydride stoichiometric mixtures with lithium hydride excess

The hydrogen sorption of mixtures of magnesium amide (Mg(NH₂)₂) and lithium hydride (LiH) with different molecular ratios have been investigated using in-situ neutron diffraction; the experiments were performed at D20/ILL and SPODI/FRMII. The results reveal a common reaction pathway for 1:2, 3:8 and 1:4 magnesium amide: lithium hydride mixtures. Intermediate reaction steps are observed in both ab- and desorption. The thermodynamic properties of the system at 200 °C are not changed by the addition of excess lithium hydride. This finding has important implications for the tailoring the characteristics of this promising hydrogen storage material.     

Environmental life cycle assessment of Italian mozzarella cheese: Hotspots and improvement opportunities

The present study investigated a cradle-to-grave life cycle assessment to estimate the environmental impacts associated with Italian mozzarella cheese consumption. The differences between mozzarella produced from raw milk and mozzarella produced from curd were studied, and differences in manufacturing processes have been emphasized in order to provide guidance for targeted improvements at this phase. Specifically, the third-largest Italian mozzarella producer was surveyed to collect site-specific manufacturing data. The Ecoinvent v3.2 database was used for secondary data, whereas SimaPro 8.1 was the modeling software. The inventory included inputs from farm activities to end of life disposal of wasted mozzarella and packaging. Additionally, plant-specific information was used to assign major inputs, such as electricity, natural gas, packaging, and chemicals to specific products; however, where disaggregated information was not provided, milk solids allocation was applied. Notably, loss of milk solids was accounted during the manufacture, moreover mozzarella waste and transport were considered during distribution, retail, and consumption phases. Feed production and animal emissions were the main drivers of raw milk production. Electricity and natural gas usage, packaging (cardboard and plastic), transport, wastewater treatment, and refrigerant loss affected the emissions from a farm gate-to-dairy plant gate perspective. Post-dairy plant gate effects were mainly determined by electricity usage for storage of mozzarella, transport of mozzarella, and waste treatment. The average emissions were 6.66 kg of CO₂ equivalents and 45.1 MJ of cumulative energy demand/kg of consumed mozzarella produced directly from raw milk, whereas mozzarella from purchased curd had larger emissions than mozzarella from raw milk due to added transport of curd from specialty manufacturing plants, as well as electricity usage from additional processes at the mozzarella plant that are required to process the curd into mozzarella. Normalization points to ecotoxicity as the impact category most significantly influenced by mozzarella consumption. From a farm gate-to-grave perspective, ecotoxicity and freshwater and marine eutrophication are the first and second largest contributors of mozzarella consumption to average European effects, respectively. To increase environmental sustainability, an improvement of efficiency for energy and packaging usage and transport activities is recommended in the post-farm gate mozzarella supply chain.     

Acid and alcohol tolerance of Escherichia coli O157:H7 in pulque, a typical Mexican beverage

Pulque is a traditional Mexican fermented alcoholic beverage produced from the nectar of maguey agave plants. No data exist on the behavior of Escherichia coli O157:H7 in agave nectar and pulque. An initial trial was done of the behavior of E. coli O157:H7 during fermentation of nectar from a single producer, a nectar mixture from different producers and "seed" pulque. A second trial simulating artisanal pulque production was done by contaminating fresh nectar with a cocktail of three E. coli O157:H7 strains, storing at 16 ° and 22 °C for 14 h, adding seed pulque and fermenting until pulque was formed. A third trial used pulque from the second trial stored at 22 °C as seed to ferment fresh nectar at 22 °C for 48 h (fermentation cycle). This procedure was repeated for an additional two fermentation cycles. During incubation at 16 ° or 22 °C in the first trial, the E. coli O157:H7 strains multiplied in both the single producer nectar and nectar mixture, reaching maximum concentration at 12h. E. coli O157:H7 cell concentration then decreased slowly, although it survived at least 72 h in both fermented nectars. E. coli O157:H7 did not multiply in the seed pulque but did survive at least 72 h. In the second trial, the numbers of E. coli O157:H7 increased approximately 1.5 log CFU/ml at 22 °C and 1.2 log CFU/ml at 16 °C after 14 h. After seed pulque was added, E. coli O157:H7 concentration decreased to approximately 2 log CFU/ml, and then remained constant until pulque was produced. In the third trial, the E. coli O157:H7 cells multiplied and survived during at least three nectar fermentation cycles. The results suggest that E. coli O157:H7 can develop acid and alcohol tolerance in pulque, and constitutes a public health risk for pulque consumers.     

Photochemical fate of carbamazepine in surface freshwaters: laboratory measures and modeling

It is shown here that carbamazepine (CBZ) would undergo direct photolysis and reaction with (?)OH as the main phototransformation pathways in surface waters. Environmental lifetimes are expected to vary from a few weeks to several months, and predictions are in good agreement with available field data. Acridine (I) and 10,11-dihydro-10,11-trans-dihydroxy-CBZ (V) are the main quantified phototransformation intermediates upon direct photolysis and (?)OH reaction, respectively. The photochemical yield of mutagenic I from CBZ is in the 3-3.5% range, and it is similar for both direct photolysis and (?)OH reaction: it would undergo limited variation with environmental conditions. In contrast, the yield of V would vary in the 4-8.5% range depending on the conditions, because V is formed from CBZ by (?)OH (9.0% yield) more effectively than upon direct photolysis (1.4% yield). Other important photointermediates, mostly formed from CBZ upon (?)OH reaction, are an aromatic-ring-dihydroxylated CBZ (VI) and N,N-bis(2-carboxyphenyl)urea (VII). Compounds VI and VII are formed by photochemistry and are not reported as human metabolites; thus, they could be used as tracers of CBZ phototransformation in surface waters. Interestingly, VI has recently been detected in river water.