Hybrid Photonic Nanostructures by In Vivo Incorporation of an Organic Fluorophore into Diatom Algae

Biotechnological processes harnessing living organisms' metabolism are low‐cost routes to nanostructured materials for applications in photonics, electronics, and nanomedicine. In the pursuit of photonic biohybrids, diatoms microalgae are attractive given the properties of the porous micro‐to‐nanoscale structures of the biosilica shells (frustules) they produce. The investigations have focused on in vivo incorporation of tailored molecular fluorophores into the frustules of Thalassiosira weissflogii diatoms, using a procedure that paves the way for easy biotechnological production of photonic nanostructures. The procedure ensures uniform staining of shells in the treated culture and permits the resulting biohybrid photonic nanostructures to be isolated with no damage to the dye and periodic biosilica network. Significantly, this approach ensures that light emission from the dye embedded in the isolated biohybrid silica is modulated by the silica's nanostructure, whereas no modulation of photoluminescence is observed upon grafting the fluorophore onto frustules by an in vitro approach based on surface chemistry. These results pave the way to the possibility of easy production of photonic nanostructures with tunable properties by simple feeding the diatoms algae with tailored photoactive molecules.     

Reduced Levels of ABCA1 Transporter Are Responsible for the Cholesterol Efflux Impairment in β-Amyloid-Induced Reactive Astrocytes: Potential Rescue from Biomimetic HDLs

The cerebral synthesis of cholesterol is mainly handled by astrocytes, which are also responsible for apoproteins’ synthesis and lipoproteins’ assembly required for the cholesterol transport in the brain parenchyma. In Alzheimer disease (AD), these processes are impaired, likely because of the astrogliosis, a process characterized by morphological and functional changes in astrocytes. Several ATP-binding cassette transporters expressed by brain cells are involved in the formation of nascent discoidal lipoproteins, but the effect of beta-amyloid (Aβ) assemblies on this process is not fully understood. In this study, we investigated how of Aβ_1-42-induced astrogliosis affects the metabolism of cholesterol in vitro. We detected an impairment in the cholesterol efflux of reactive astrocytes attributable to reduced levels of ABCA1 transporters that could explain the decreased lipoproteins’ levels detected in AD patients. To approach this issue, we designed biomimetic HDLs and evaluated their performance as cholesterol acceptors. The results demonstrated the ability of apoA-I nanodiscs to cross the blood–brain barrier in vitro and to promote the cholesterol efflux from astrocytes, making them suitable as a potential supportive treatment for AD to compensate the depletion of cerebral HDLs.     

Beneficial and Sexually Dimorphic Response to Combined HDAC Inhibitor Valproate and AMPK/SIRT1 Pathway Activator Resveratrol in the Treatment of ALS Mice

Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disorder. There is no cure and current treatments fail to slow the progression of the disease. Epigenetic modulation in the acetylation state of NF-kB RelA and the histone 3 (H3) protein, involved in the development of neurodegeneration, is a drugable target for the class-I histone deacetylases (HDAC) inhibitors, entinostat or valproate, and the AMP-activated kinase (AMPK)-sirtuin 1 pathway activator, resveratrol. In this study, we demonstrated that the combination of valproate and resveratrol can restore the normal acetylation state of RelA in the SOD1(G93A) murine model of ALS, in order to obtain the neuroprotective form of NF-kB. We also investigated the sexually dimorphic development of the disease, as well as the sex-sensibility to the treatment administered. We showed that the combined drugs, which rescued AMPK activation, RelA and the histone 3 acetylation state, reduced the motor deficit and the disease pathology associated with motor neuron loss and microglial reactivity, Brain-Derived Neurotrophic Factor (BDNF) and B-cell lymphoma-extra large (Bcl-xL) level decline. Specifically, vehicle-administered males showed earlier onset and slower progression of the disease when compared to females. The treatment, administered at 50 days of life, postponed the time of onset in the male by 22 days, but not in a significant way in females. Nevertheless, in females, the drugs significantly reduced symptom severity of the later phase of the disease and prolonged the mice’s survival. Only minor beneficial effects were produced in the latter stage in males. Overall, this study shows a beneficial and sexually dimorphic response to valproate and resveratrol treatment in ALS mice.     

miRNA Expression Profiling in Subcutaneous Adipose Tissue of Monozygotic Twins Discordant for HIV Infection: Validation of Differentially Expressed miRNA and Bioinformatic Analysis

Combined AntiRetroviral Treatments (cARTs) used for HIV infection may result in varied metabolic complications, which in some cases, may be related to patient genetic factors, particularly microRNAs. The use of monozygotic twins, differing only for HIV infection, presents a unique and powerful model for the controlled analysis of potential alterations of miRNAs regulation consequent to cART treatment. Profiling of 2578 mature miRNA in the subcutaneous (SC) adipose tissue and plasma of monozygotic twins was investigated by the GeneChip^® miRNA 4.1 array. Real-time PCR and ddPCR experiments were performed in order to validate differentially expressed miRNAs. Target genes of deregulated miRNAs were predicted by the miRDB database (prediction score > 70) and enrichment analysis was carried out with g:Profiler. Processes in SC adipose tissue most greatly affected by miRNA up-regulation included (i) macromolecular metabolic processes, (ii) regulation of neurogenesis, and (iii) protein phosphorylation. Furthermore, KEGG analysis revealed miRNA up-regulation involvement in (i) insulin signaling pathways, (ii) neurotrophin signaling pathways, and (iii) pancreatic cancer. By contrast, miRNA up-regulation in plasma was involved in (i) melanoma, (ii) p53 signaling pathways, and (iii) focal adhesion. Our findings suggest a mechanism that may increase the predisposition of HIV⁺ patients to insulin resistance and cancer.     

Effects of Sedentarism and Treadmill Training in Mechanical Properties of Muscles of Ovariectomized Rats with High-Fat Diet

The aim of this study is to evaluate the ability of physical training in the maintenance of muscle strength in rats with HFD （high-fat diet） after OVX （ovariectomy）. Eighty Wistar rats are at eight weeks of age and weight 200 g which divided into 8 groups （n = 10） and treated for 12 weeks： GA： OVX ＋ ND （normal diet）, GB： OVX ＋ ND ＋ training, GC： sham ＋ ND, GD： sham ＋ ND ＋ training, GE： OVX ＋ HFD, GF： OVX ＋ HFD ＋ training, GG： sham ＋ HFD and GH： sham ＋ HFD ＋ training. HFD consists of standard ration for rats with addition of 30% lipids. In training groups, physical training five training/week was conducted on a treadmill with adaptation period of three weeks up to 18 m/s for one hour, training were performed for 12 weeks. The sedentary animals remained in individual box. To analyze the effects of training and diet, tensile strength tests of the gastrocnemius muscles were conducted： the speed of 0.1 mm/min. Analysis of variance was performed to compare groups. The mean （SD） obtained for the maximum load （N） were： GA 57.77 （6.89）, GB 62.74 （5.07）, GC 49.45 （6.06）, GD 59.42 （5.26） and GE 55.58 （4.72）, GF 62.50 （4.56）, GG 58.35 （4.54） and GH 56.67 （5.87）, respectively. There were no differences for maximum load between surgeries （p = 0.004） and between treatments （p = 0.000）. Differences were found also for the relationship surgery diet treatment （p = 0.007）. For the variable stiffness （N/mm）, there were not statistically significant differences： GA 5.03 （0.72）, GB 5.08 （1.09）, GC 5.17 （0.53）, GD 5.35 （0.80）, GE 5.52 （1.20）, GF 5.36 （1.07）, GG 4.83 （1.03） and GH 5.40 （0.73）. For the toughness （N/mm）, there were differences between treatments （p = 0.010） and the ratio diet treatment （p = 0.024）： GA 455.00 （107.21）, GB 541.96 （126.80）, GC 394.97 （84.67）, GD 566.90 （157.07）; GE 424.63 （113.03）, GF 478.07 （106.03）; GG 517.44 （98.65?     

Exploitation of the Antibacterial Properties of Photoactivated Curcumin as ‘Green’ Tool for Food Preservation

In the search for non-chemical and green methods to counteract the bacterial contamination of foods, the use of natural substances with antimicrobial properties and light irradiation at proper light waves has been extensively investigated. In particular, the combination of both techniques, called photodynamic inactivation (PDI), is based on the fact that some natural substances act as photosensitizers, i.e., produce bioactive effects under irradiation. Notably, curcumin is a potent natural antibacterial and effective photosensitizer that is able to induce photodynamic activation in the visible light range (specifically for blue light). Some practical applications have been investigated with particular reference to food preservation from bacterial contaminants.     

The Generation of Nitric Oxide from Aldehyde Dehydrogenase-2: The Role of Dietary Nitrates and Their Implication in Cardiovascular Disease Management

Reduced bioavailability of the nitric oxide (NO) signaling molecule has been associated with the onset of cardiovascular disease. One of the better-known and effective therapies for cardiovascular disorders is the use of organic nitrates, such as glyceryl trinitrate (GTN), which increases the concentration of NO. Unfortunately, chronic use of this therapy can induce a phenomenon known as “nitrate tolerance”, which is defined as the loss of hemodynamic effects and a reduction in therapeutic effects. As such, a higher dosage of GTN is required in order to achieve the same vasodilatory and antiplatelet effects. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is a cardioprotective enzyme that catalyzes the bio-activation of GTN to NO. Nitrate tolerance is accompanied by an increase in oxidative stress, endothelial dysfunction, and sympathetic activation, as well as a loss of the catalytic activity of ALDH2 itself. On the basis of current knowledge, nitrate intake in the diet would guarantee a concentration of NO such as to avoid (or at least reduce) treatment with GTN and the consequent onset of nitrate tolerance in the course of cardiovascular diseases, so as not to make necessary the increase in GTN concentrations and the possible inhibition/alteration of ALDH2, which aggravates the problem of a positive feedback mechanism. Therefore, the purpose of this review is to summarize data relating to the introduction into the diet of some natural products that could assist pharmacological therapy in order to provide the NO necessary to reduce the intake of GTN and the phenomenon of nitrate tolerance and to ensure the correct catalytic activity of ALDH2.     

In Vitro Selection of Lactobacillus and Bifidobacterium Probiotic Strains for the Management of Oral Pathobiont Infections Associated to Systemic Diseases

The human oral pathobionts Aggregatibacter actinomycetemcomitans, Streptococcus mitis and Streptococcus mutans, in dysbiosis-promoting conditions, lead to oral infections, which also represent a threat to human systemic health. This scenario may be worsened by antibiotic misuse, which favours multi-drug resistance, making the research on pathogen containment strategies more than crucial. Therefore, we aimed to in vitro select the most promising probiotic strains against oral pathogen growth, viability, biofilm formation, and co-aggregation capacity, employing both the viable probiotics and their cell-free supernatants (CFSs). Interestingly, we also assessed probiotic efficacy against the three-pathogen co-culture, mimicking an environment similar to that in vivo. Overall, the results showed that Lactobacillus CFSs performed better than the Bifidobacterium, highlighting Limosilactobacillus reuteri LRE11, Lacticaseibacillus rhamnosus LR04, Lacticaseibacillus casei LC04, and Limosilactobacillus fermentum LF26 as the most effective strains, opening the chance to deeper investigation of their action and CFS composition. Altogether, the methodologies presented in this study can be used for probiotic efficacy screenings, in order to better focus the research on a viable probiotic, or on its postbiotics, suitable in case of infections.