The Age-Sensitive Efficacy of Calorie Restriction on Mitochondrial Biogenesis and mtDNA Damage in Rat Liver

Calorie restriction (CR) is the most efficacious treatment to delay the onset of age-related changes such as mitochondrial dysfunction. However, the sensitivity of mitochondrial markers to CR and the age-related boundaries of CR efficacy are not fully elucidated. We used liver samples from ad libitum-fed (AL) rats divided in: 18-month-old (AL-18), 28-month-old (AL-28), and 32-month-old (AL-32) groups, and from CR-treated (CR) 28-month-old (CR-28) and 32-month-old (CR-32) counterparts to assay the effect of CR on several mitochondrial markers. The age-related decreases in citrate synthase activity, in TFAM, MFN2, and DRP1 protein amounts and in the mtDNA content in the AL-28 group were prevented in CR-28 counterparts. Accordingly, CR reduced oxidative mtDNA damage assessed through the incidence of oxidized purines at specific mtDNA regions in CR-28 animals. These findings support the anti-aging effect of CR up to 28 months. Conversely, the protein amounts of LonP1, Cyt c, OGG1, and APE1 and the 4.8 Kb mtDNA deletion content were not affected in CR-28 rats. The absence of significant differences between the AL-32 values and the CR-32 counterparts suggests an age-related boundary of CR efficacy at this age. However, this only partially curtails the CR benefits in counteracting the generalized aging decline and the related mitochondrial involvement.     

Exploring Molecular Contacts of MUC1 at CIN85 Binding Interface to Address Future Drug Design Efforts

The modulation of protein-protein interactions (PPIs) by small molecules represents a valuable strategy for pharmacological intervention in several human diseases. In this context, computer-aided drug discovery techniques offer useful resources to predict the network of interactions governing the recognition process between protein partners, thus furnishing relevant information for the design of novel PPI modulators. In this work, we focused our attention on the MUC1-CIN85 complex as a crucial PPI controlling cancer progression and metastasis. MUC1 is a transmembrane glycoprotein whose extracellular domain contains a variable number of tandem repeats (VNTRs) regions that are highly glycosylated in normal cells and under-glycosylated in cancer. The hypo-glycosylation fosters the exposure of the backbone to new interactions with other proteins, such as CIN85, that alter the intracellular signalling in tumour cells. Herein, different computational approaches were combined to investigate the molecular recognition pattern of MUC1-CIN85 PPI thus unveiling new structural information useful for the design of MUC1-CIN85 PPI inhibitors as potential anti-metastatic agents.     

Cachexia,a Systemic Disease beyond Muscle Atrophy

Cachexia is a complication of dismal prognosis, which often represents the last step of several chronic diseases. For this reason, the comprehension of the molecular drivers of such a condition is crucial for the development of management approaches. Importantly, cachexia is a syndrome affecting various organs, which often results in systemic complications. To date, the majority of the research on cachexia has been focused on skeletal muscle, muscle atrophy being a pivotal cause of weight loss and the major feature associated with the steep reduction in quality of life. Nevertheless, defining the impact of cachexia on other organs is essential to properly comprehend the complexity of such a condition and potentially develop novel therapeutic approaches.     

Milk from cows fed a diet with a high forage:concentrate ratio improves inflammatory state,oxidative stress,and mitochondrial function in rats

Excessive energy intake may evoke complex biochemical processes characterized by inflammation, oxidative stress, and impairment of mitochondrial function that represent the main factors underlying noncommunicable diseases. Because cow milk is widely used for human nutrition and in food industry processing, the nutritional quality of milk is of special interest with respect to human health. In our study, we analyzed milk produced by dairy cows fed a diet characterized by a high forage:concentrate ratio (high forage milk, HFM). In view of the low n-6:n-3 ratio and high content of conjugated linoleic acid of HFM, we studied the effects of this milk on lipid metabolism, inflammation, mitochondrial function, and oxidative stress in a rat model. To this end, we supplemented for 4 wk the diet of male Wistar rats with HFM and with an isocaloric amount (82 kJ, 22 mL/d) of milk obtained from cows fed a diet with low forage:concentrate ratio, and analyzed the metabolic parameters of the animals. Our results indicate that HFM may positively affect lipid metabolism, leptin:adiponectin ratio, inflammation, mitochondrial function, and oxidative stress, providing the first evidence of the beneficial effects of HFM on rat metabolism.     

Macrophage Immunomodulation Through New Polymers that Recapitulate Functional Effects of Itaconate as a Power House of Innate Immunity

Itaconate (ITA) is an emerging powerhouse of innate immunity with therapeutic potential that is limited in its ability to be administered in a soluble form. A library of polyester materials that incorporate ITA into polymer backbones resulting in materials with inherent immunoregulatory behavior is developed. Harnessing hydrolytic degradation release from polyester backbones, ITA polymers result in the mechanism specific immunoregulatory properties on macrophage polarization in vitro. In a functional assay, the polymer-released ITA inhibits bacterial growth on acetate. Translation to an in vivo model of biomaterial associated inflammation, intraperitoneal injection of ITA polymers demonstrate a rapid resolution of inflammation in comparison to a control polymer silicone, demonstrating the value of sustained biomimetic presentation of ITA.     

Workers’ rest allowance and smoothing of the workload in assembly lines

Ergonomic aspects have a crucial role in manual assembly systems. They impact on the workers’ health, final product quality and productivity. For these reasons, there is the necessity to integrate them into the assembly line balancing phase as, whereas, only time and cost variables are considered. In this study, human energy expenditures are considered as ergonomic aspects and we integrate them, for the first time, into the assembly line balancing problem type 2 through the rest allowance evaluation. We consider as an objective function the minimization of the smoothness index. Firstly, a new optimal method based on mixed integer linear programming and a new linearization methodology are proposed. Then, a heuristic approach is introduced. To complete the study, a computational experimentation is presented to validate the mathematical model and to compare the methodologies proposed in terms of computational time, complexity and solution. Additionally, we provide a detailed analysis of the impact that rest allowance evaluation can have on productivity comparing the results obtained, taking into account the rest allowance integration before, during and after the assembly balancing process.     

Polymer brush coatings for combating marine biofouling

A variety of functional polymer brushes and coatings have been developed for combating marine biofouling and biocorrosion with much less environmental impact than traditional biocides. This review summarizes recent developments in marine antifouling polymer brushes and coatings that are tethered to material surfaces and do not actively release biocides. Polymer brush coatings have been designed to inhibit molecular fouling, microfouling and macrofouling through incorporation or inclusion of multiple functionalities. Hydrophilic polymers, such as poly(ethylene glycol), hydrogels, zwitterionic polymers and polysaccharides, resist attachment of marine organisms effectively due to extensive hydration. Fouling release polymer coatings, based on fluoropolymers and poly(dimethylsiloxane) elastomers, minimize adhesion between marine organisms and material surfaces, leading to easy removal of biofoulants. Polycationic coatings are effective in reducing marine biofouling partly because of their good bactericidal properties. Recent advances in controlled radical polymerization and click chemistry have also allowed better molecular design and engineering of multifunctional brush coatings for improved antifouling efficacies.