Biodegradable multi-walled carbon nanotubes trigger anti-tumoral effects.

Carbon nanotubes are of huge biotechnological interest because they can penetrate most biological barriers and, inside cells, can biomimetically interact with the cytoskeletal filaments, triggering anti-proliferative and cytotoxic effects in highly dividing cells. Unfortunately, their intrinsic properties and bio-persistence represent a putative hazard that relapses their application as therapies against cancer. Here we investigate mild oxidation treatments to improve the intracellular enzymatic digestion of MWCNTs, but preserving their morphology, responsible for their intrinsic cytotoxic properties. Cell imaging techniques and confocal Raman spectroscopic signature analysis revealed that cultured macrophages can degrade bundles of oxidized MWCNTs (o-MWCNTs) in a few days. The isolation of nanotubes from these phagocytes 96 hours after exposure confirmed a significant reduction of approximately 30% in the total length of these filaments compared to the control o-MWCNTs extracted from the cell culture medium, or the intracellular pristine MWCNTs. More interestingly, in vivo single intratumoral injections of o-MWCNTs triggered ca. 30% solid melanoma tumour growth-inhibitory effects while displaying significant signs of biodegradation at the tumoral/peri-tumoral tissues a week after the therapy has had the effect. These results support the potential use of o-MWCNTs as antitumoral agents and reveal interesting clues of how to enhance the efficient clearance of in vivo carbon nanotubes.

Quasiclassical trajectory study of the effect of antisymmetric stretch mode excitation on the O(³P) + CH4(ν3 = 1) → OH + CH3 reaction on an analytical potential energy surface. Comparison with experiment.

Motivated by a recent crossed-beam experiment on the title reaction reported by Pan and Liu [J. Chem. Phys. 140, 191101 (2014)], a detailed dynamics study was performed at three collision energies using quasiclassical trajectory (QCT) calculations based on a full-dimensional potential energy surface recently developed by our group (PES-2014). Although theory/experiment agreement is not yet quantitative, in general the theoretical results reproduce the experimental evidence: the vibrational branching ratio of OH(v = 1)/OH(v = 0) is ~0.8/0.2, excitation of the antisymmetric CH stretching mode in methane increases reactivity by factor 2.28-1.50, although an equivalent amount as translational energy is more efficient in promoting the reaction and, finally, product angular distribution shifts from backward in the CH4(ν = 0) ground-state to sideways when the antisymmetric CH stretching mode is excited. These results give confidence to the PES-2014 surface, depend on the quantization procedure used, are comparable with recent QCT calculations or improve previous theoretical studies using a different surface, and demonstrate the utility of the theory/experiment collaboration.

Dynamics of the O(3P) + CH4 hydrogen abstraction reaction at hyperthermal collision energies.

Motivated by recent experiments on the title reaction at the high collision energy of 64 kcal mol(-1) reported by Minton et al., a detailed dynamics study was carried out using quasi-classical trajectory (QCT) calculations based on an analytical potential energy surface recently developed by our group, PES-2014. Our results reproduce the experimental evidence: most of the available energy appears as translational energy (80 ± 10%) and scattering distribution is forward, suggesting a stripping mechanism associated with high impact parameters. Of special interest is the triple (angle-velocity) differential cross section (a combination of translational and scattering distributions), which shows the same structure associated with the products. Agreement with experiment lends confidence to the new PES-2014 surface; this is encouraging, furthermore, because its fitting was made with thermal behaviour in mind, and higher energy areas were neither sampled nor weighted sufficiently.

Oxidative stress is associated with liver damage, inflammatory status, and corticosteroid therapy in patients with systemic lupus erythematosus.

Oxidative stress exerts an important role on the pathophysiological mechanisms of systemic lupus erythematosus (SLE). This study investigated oxidative stress in patients with SLE and its correlation with disease activity, corticosteroid therapy, and liver function biomarkers. The study included 58 patients with SLE and 105 healthy volunteers. Patients showed oxidative stress increase evaluated by tert-butyl hydroperoxide-initiated chemiluminescence (CL-LOOH), advanced oxidation protein products (AOPP), and nitric oxide metabolites. C-reactive protein (CRP) was associated with CL-LOOH and with AOPP. Aspartate aminotransferase correlated significantly with CL-LOOH and with AOPP. Patients with disease activity showed an inverse significant correlation of daily prednisone doses and CL-LOOH and a direct correlation with total antioxidant capacity. In conclusion, patients with SLE have persistent lipoperoxidation and protein oxidation even with inactive disease or mild disease activity. The significant correlation between oxidative stress and CRP suggests that, despite clinical remission, the persistence of an inflammatory condition favors oxidative stress. Oxidative stress was associated with liver enzymes, and this relationship seems to support the hypothesis of drug-induced oxidative stress with consequent liver injury. In relation to non-active disease, patients with active SLE did not present oxidative stress and antioxidant capacity changes, due to the antioxidant drugs used in SLE treatment, especially prednisone.

Facial exercise therapy for facial palsy: systematic review and meta-analysis.

UNLABELLED: The effectiveness of facial exercises therapy for facial palsy has been debated in systematic reviews but its effects are still not totally explained. OBJECTIVE: To perform a systematic review with meta-analysis to evaluate the effects of facial exercise therapy for facial palsy. DATA SOURCES: A search was performed in the following databases: Cochrane Controlled Trials Register Library, Cochrane Disease Group Trials Register, MEDLINE, EMBASE, LILACS, PEDro, Scielo and DARE from 1966 to 2010; the following keywords were used: 'idiopathic facial palsy', 'facial paralysis', 'Bell's palsy', 'physical therapy', 'exercise movement techniques', 'facial exercises', 'mime therapy' 'facial expression', 'massage' and 'randomized controlled trials'. REVIEW METHODS: The inclusion criteria were studies with facial exercises, associated or not with mirror biofeedback, to treat facial palsy. RESULTS: One hundred and thirty-two studies were found but only six met the inclusion criteria. All the studies were evaluated by two independent reviewers, following the recommendations of Cochrane Collaboration Handbook for assessment of risk of bias (kappa coefficient = 0.8). Only one study presented sufficient data to perform the meta-analysis, and significant improvements in functionality was found for the experimental group (standardized mean difference (SMD) = 13.90; 95% confidence interval (CI) 4.31, 23.49; P = 0.005). CONCLUSION: Facial exercise therapy is effective for facial palsy for the outcome functionality.

Neuronal differentiation is triggered by oleic acid synthesized and released by astrocytes.

Unlike in the adult brain, the newborn brain specifically takes up serum albumin during the postnatal period, coinciding with the stage of maximal brain development. Here we report that albumin stimulates oleic acid synthesis by astrocytes from the main metabolic substrates available during brain development. Oleic acid released by astrocytes is used by neurons for the synthesis of phospholipids and is specifically incorporated into growth cones. Oleic acid promotes axonal growth, neuronal clustering, and expression of the axonal growth-associated protein-43, GAP-43; all these observations indicating neuronal differentiation. The effect of oleic acid on GAP-43 synthesis is brought about by the activation of protein kinase C, since it was prevented by inhibitors of this kinase, such as H-7, polymyxin or sphingosine. The expression of GAP-43 was significantly increased in neurons co-cultured with astrocytes by the presence of albumin indicating that neuronal differentiation takes place in the presence of oleic acid synthesized and released by astrocytes in situ. In conclusion, during brain development the presence of albumin could play an important role by triggering the synthesis and release of oleic acid by astrocytes, which induces neuronal differentiation.

Organization and transcriptional analysis of a six-gene cluster around the rplK-rplA operon of Corynebacterium glutamicum encoding the ribosomal proteins L11 and L1.

A cluster of six genes, tRNA(Trp)-secE-nusG-rplK-rplA-pkwR, was cloned and sequenced from a Corynebacterium glutamicum cosmid library and shown to be contiguous in the C. glutamicum genome. These genes encode a tryptophanyl tRNA, the protein translocase component SecE, the antiterminator protein NusG, and the ribosomal proteins L11 and L1 in addition to PkwR, a putative regulatory protein of the LacI-GalR family. S1 nuclease mapping analysis revealed that nusG and rplK are expressed as separate transcriptional units and rplK and rplA are cotranscribed as a single mRNA. A 19-nucleotide inverted repeat that appears to correspond to a transcriptional terminator was located in the 3' region downstream from nusG. Northern analysis with different probes confirmed the S1 mapping results and showed that the secE-rplA four-gene region gives rise to four transcripts. secE was transcribed as a 0.5-kb monocistronic mRNA, nusG formed two transcripts of 1.4 and 1.0 kb from different initiation sites, and the two ribosomal protein genes rplK and rplA were cotranscribed as a single mRNA of 1.6 kb. A consensus L1 protein binding sequence was identified in the leader region of the rplK-rplA transcript, suggesting that expression of the rplK-rplA cluster was regulated by autogenous regulation exerted by the L1 protein at the translation level. The promoters of the nusG and rplK-rplA genes were subcloned in a novel corynebacterial promoter-probe vector and shown to confer strong expression of the reporter gene.

The effect of albumin on astrocyte energy metabolism is not brought about through the control of cytosolic Ca2+ concentrations but by free-fatty acid sequestration.

Albumin is an important serum protein that under normal circumstances is not present in the brain. However, during development, under hypoxia, or after breakdown of the blood-brain barrier, albumin is found in the brain, where it is able to regulate energy metabolism. In this work the mechanism through which albumin regulates astrocyte metabolism was investigated. Our results show that albumin strongly increases (more than 100%) the flux of glucose and lactate through the pyruvate dehydrogenase-catalyzed reaction in astrocytes from primary culture. However, albumin only slightly stimulated other metabolic pathways, such as the tricarboxylic acid cycle or the pentose phosphate shunt, indicating that it exerts its effect specifically on the reaction catalyzed by pyruvate dehydrogenase. Although albumin increased cytosolic Ca2+ concentrations in astrocytes, our results show that the increase in pyruvate dehydrogenase activity promoted by albumin is not due to the enhancement of Ca2+ concentrations. Indeed, highly purified albumins failed to increase the Ca2+ concentration but did enhance lactate oxidation. In agreement with this, the effect of albumin on lactate oxidation was not abolished after Ca2+ depletion. Instead, the presence of fatty acids inhibited lactate oxidation and counteracted the effect of albumin, suggesting that albumin activates pyruvate dehydrogenase by binding free fatty acids and/or their CoA-derivatives.

Oleic acid inhibits gap junction permeability and increases glucose uptake in cultured rat astrocytes.

The role of oleic acid in the modulation of gap junction permeability was studied in cultured rat astrocytes by the scrape-loading/Lucifer yellow transfer technique. Incubation with oleic acid caused a dose-dependent inhibition of gap junction permeability by 79.5% at 50 microM, and no further inhibition was observed by increasing the oleic acid concentration to 100 microM. The oleic acid-mediated inhibition of gap junction permeability was reversible and was prevented by bovine serum albumin. The potency of oleic acid-related compounds in inhibiting gap junction permeability was arachidonic acid > oleic acid > oleyl alcohol > palmitoleic acid > stearic acid > octanol > caprylic acid > palmitic acid > methyloleyl ester. Oleic acid and arachidonic acid, but not methyloleyl ester, increased glucose uptake by astrocytes. Neither oleic acid nor arachidonic acid increased glucose uptake in the poorly coupled glioma C6 cells. These results support that the inhibition of gap junction permeability is associated with the increase in glucose uptake. We suggest that oleic acid may be a physiological mediator of the transduction pathway leading to the inhibition of intercellular communication.