The best of both worlds:mastering nerve regeneration combining biological and nanotechnological tools

Over the last decade,remarkable developments in nanotechnology have powered medical research,unveiling new approaches for the solution of public health issues such as the treatment of traumatic peripheral neuropathies.

Chemical profile and antimicrobial activity of Secondatia floribunda A. DC(Apocynaceae)

To establish the chemical profile, and to evaluate the antibacterial and modulatory activity of the ethanolic extracts of the stalk’s inner bark and heartwood of Secondatia floribunda.MethodsQuantification of total phenols and flavonoids was determined by the Folin-Ciocalteu method and aluminum chloride, respectively. Phenolic compounds were identified and quantified by HPLC-DAD (High Performance Liquid Chromatography-Diodearray Detector) and the Infrared Spectroscopy was performed using the measure by Attenuated Total Reflectance with Fourier Transform (ATR-FTIR). Antibacterial assays for determination of the Minimum Inhibitory Concentration (MIC) and modification of aminoglycosides were performed by microdilution.ResultsInfrared spectra showed similar characteristics, having among its main absorption bands hydroxyl group (OH). The antibacterial activity showed clinically significant results for the strains of Staphylococcus aureus and Escherichia coli. In modulation assay, synergic and antagonistic effect for both extracts was observed. Heartwood extract in combination with antibiotics showed a significant MIC reduction at 19.8% (P < 0.000 1)-79.3% (P < 0.01).ConclusionsThis study is the first report of chemical and biological information of Secondatia floribunda suggesting that it is clinically relevant source of a new antibacterial therapy, especially due to the presence of significant levels of phenolic compounds.

Glutamine is highly effective in preventing in vivo cobalt-induced oxidative stress in rat liver

AIM: To evaluate the in vivo effect of glutamine on cobaltgenerated oxidative stress and (HO-1) induction in rat liver.METHODS: Fasted female Wistar rats received a single injection of cobalt chloride (375 μmol/kg body weight) and then were killed at different times. Lipid peroxidation and soluble and enzymatic antioxidant defense system (reduced glutathione (GSH), catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD)) were measured in liver homogenates. Ferritin and ferritin iron contents as well as heme oxygenase-1 (HO-1) activity and expression were also determined. The antioxidant properties of glutamine (Gin) were also evaluated. RESULTS: Cobalt chloride increased lipid peroxidation (50% over control values) 1 h after treatment. GSH reached a minimum at 3 h (40%) increasing thereafter. Twelve hours after CoCl2 injection, the antioxidant enzymes CAT, GSH-Px and SOD also diminished by about 30%. Heme oxygenase-1 induction was observed 6 h after treatment reaching a maximum value of 14-fold over the controls, 12 h after cobalt treatment. A 1.7-fold increase in ferritin and ferritin-bound iron 24 h after treatment were also obtained. Administration of glutamine (300 mg/kg body weight) by gavage 24 h before CoCl2 treatment entirely prevented the increase in thiobarbituric acid reactive substances (TBARS) content, the decrease in GSH levels, and partially reverted heme oxygenase-1 induction. CONCLUSION: These results suggested that a natural product such as glutamine prevents glutathione depletion and consequently heme oxygenase induction.

Microglia depletion as a therapeutic strategy:friend or foe in multiple sclerosis models?

M ultiple sclerosis is a chro nic central nervous system demyelinating disease whose onset and progression are driven by a combination of immune dysregulation,genetic predisposition,and environmental fa ctors.The activation of microglia and astrocytes is a key player in multiple sclerosis immunopathology,playing specific roles associated with anatomical location and phase of the disease and controlling demyelination and neurodegeneration.Even though reactive mic roglia can damage tissue and heighten deleterious effects and neurodegeneration,activated microglia also perform neuroprotective functions such as debris phagocytosis and growth fa ctor secretion.Astrocytes can be activated into pro-inflammato ry phenotype A1 through a mechanism mediated by activated neuroinflammatory microglia,which could also mediate neurodegeneration.This A1 phenotype inhibits oligodendrocyte prolife ration and differe ntiation and is toxic to both oligodendrocytes and neurons.Howeve r,astroglial activation into phenotype A2 may also take place in response to neurodegeneration and as a protective mechanism.A variety of animal models mimicking specific multiple sclerosis features and the associated pathophysiological processes have helped establish the cascades of events that lead to the initiation,progression,and resolution of the disease.The colonystimulating facto r-1 receptor is expressed by myeloid lineage cells such as peripheral monocytes and macrophages and central nervous system microglia.Importantly,as microglia development and survival critically rely on colony-stimulating factor-1 receptor signaling,colony-stimulating factor-1 receptor inhibition can almost completely eliminate microglia from the brain.In this context,the present review discusses the impact of microglial depletion through colo ny-stimulating factor-1 receptor inhibition on demyelination,neurodegeneration,astroglial activation,and behavior in different multiple sclerosis models,highlighting the diversity of microglial effects on the progression of demyelinating diseases and the strengths and weaknesses of microglial modulation in therapy design.

CD4+ T cells and natural killer cells: Biomarkers for hepatic fibrosis in human immunodeficiency virus/hepatitis C virus-coinfected patients

AIM To characterize peripheral blood natural killer(NK) cells phenotypes by flow cytometry as potential biomarker of liver fibrosis in human immunodeficiency virus(HIV)/hepatitis C virus(HCV) coinfected patients.METHODS Peripheral mononuclear cells from 24 HIV/HCV(HBVnegative) coinfected and 5 HIV/HCV/HBV seronegative individuals were evaluated. HIV/HCV coinfected patients were divided in to groups: G1, patients with METAVIR F0-F2 and G2, patients with METAVIR F3-F4. NK surface cell staining was performed with: AntiCD3(APC/Cy7), anti-CD56(PE/Cy5), anti-CD57(APC), anti-CD25(PE), anti-CD69(FITC), anti-NKp30(PE), antiNKp46(PE/Cy7), anti-NKG2D(APC), anti-DNAM(FITC); anti-CD62L(PE/Cy7), anti-CCR7(PE), anti-TRAIL(PE), anti-Fas L(PE), anti CD94(FITC). Flow cytometry data acquisition was performed on BD FACSCanto, analyzed using Flow Jo software. Frequency of fluorescence was analyzed for all single markers. Clinical records were reviewed, and epidemiological and clinical data were obtained.RESULTS Samples from 11 patients were included in G1 and from 13 in G2. All patients were on ARV, with undetectable HIV viral load. Liver fibrosis was evaluated by transient elastography in 90% of the patients and with biopsy in 10% of the patients. Mean HCV viral load was(6.18 ± 0.7 log10). Even though, no major significant differences were observed between G1 and G2 regarding NK surface markers, it was found that patients with higher liver fibrosis presented statistically lower percentage of NK cells than individual with low to mild fibrosis and healthy controls(G2: 5.4% ± 2.3%, G1: 12.6% ± 8.2%, P = 0.002 and healthy controls 12.2% ± 2.7%, P = 0.008). It was also found that individuals with higher liver fibrosis presented lower CD4 LT count than those from G1(G2: 521 ± 312 cells/μL, G1: 770 ± 205 cells/μL; P = 0.035).CONCLUSION Higher levels of liver fibrosis were associated with lower percentage of NK cells and LTCD4+ count; and they may serve as noninvasive biomarkers of liver damage.

Antibacterial activity and inhibition against Staphylococcus aureus NorA efflux pump by ferulic acid and its esterified derivatives

Objective:To evaluate the inhibitory activity of ferulic acid and four of its esterified derivatives(methyl,ethyl,propyl,and butyl)against resistance mechanisms in Staphylococcus aureus strains.Methods:Ferulic acid derivatives were obtained by esterification with methanol,ethanol,propanol,and butanol,and then characterized by hydrogen and carbon-13 nuclear magnetic resonance analysis.The minimum inhibitory concentrations(MIC)of ferulic acid and its esterified derivatives,ethidium bromide,and norfloxacin were obtained using the microdilution test,while the efflux pump inhibition test was conducted by examining reduction in the MICs of norfloxacin and ethidium bromide.Molecular docking was also carried out using the Schrodinger Suite 2015 molecular modeling software.A three-dimensional model of NorA efflux pump was generated using I-TASSER.The best scoring model was used as a receptor for ligand-receptor docking.Results:The methyl and butyl ester derivatives did not demonstrate significant antimicrobial activity.However,a significant synergic effect was evidenced when norfloxacin was combined with the ethyl and propyl esterified derivatives.The docking study demonstrated favorable energy of interaction between ferulate derivatives and NorA,and amino acid residues TYR57,TYR58,and LEU255 were present commonly in stabilizing all complexes.The PCA analysis corroborated the docking hypothesis that the lipophilic character and hydrogen bond interactions were the most relevant characteristics involved with NorA inhibitors.The pharmacokinetic parameters of ferulic acid derivatives showed good ADMET properties,demonstrating that they can be easily absorbed and have no effect or inhibit the cytochrome P450 enzyme complex,revealing their potential as drug candidates.Conclusions:This study provides strong evidence that the molecular basis for this activity is potentially due to the NorA efflux pump.

Impact of chitosan-based nanocarriers on cytoskeleton dynamics:Current status and challenges

Chitosan-based nanocarriers(CS-NCs)show a promising role in improving drugs and bioactive compounds delivery for therapy.However,the effects exerted by CS-NCs at the cellular level,including their recognition and uptake,have not been fully investigated yet.Many factors,including size,shape,concentration,and surface chemistry of CS-NCs,play an important role in determining the types of intracellular signals triggered.The mechanism of uptake and the involvement of the cytoskeleton during the CS-NCs endocytosis variates among the different cell types as well as further effects observed inside cells.In the present work,we discuss the effects induced by CS-NCs per se on the cytoskeleton,a key component in cell architecture and physiology.The focus of this report is made on tumoral and normal biological models in which CS-NCs could differentially affect the cell cytoskeleton.The recent years reports regarding the impact of CS-NCs on cytoskeleton dynamics and the current techniques for its evaluation are summarized and discussed.Understanding mechanisms underlying cytoskeletal impact after cell exposure to CS-NCs is critical for the design of safest value-added formulations in the biomedical field.Furthermore,this revision points out some interesting aspects of cytoskeletal changes and cell death encompassing anti-tumoral effects.

A study of chlorophyll-like and phycobilin pigments in the C endosymbiont of the apple- snail Pomacea canaliculata

Pigments present in the brown-greenish C morph of an intracellular endosymbiont of Pomacea canaliculata were investigated.Acetone extracts of the endosymbiotic corpuscles showed an absorption spectrum similar to that of chlorophylls.Three fractions obtained from silica gel column chromatography of the acetone extracts(CI,CII and CIII),were studied by positive ion fast atom bombardment-mass spectrometry(FAB–MS)and hydrogen-nuclear magnetic resonance(H-NMR).Results indicated the presence of(1)a sterol in the yellow colored CI fraction;(2)a mixture of pheophorbides a and b in the major green fraction,CII;and(3)a modified pheophorbide a in the smaller green fraction,CIII.Aqueous extracts of the C endosymbiont did not show evidence of the occurrence of C-phycocyanin,allophycocyanin or phycoerithrin(light absorption,fluorescence emission,and electrophoresis of the protein moieties)while cyanobacterial cells(Nostoc sp.)showed evidence of C-phycocyanin and allophycocyanin.The possible phylogenetic and functional significance of the pigments present in the C endosymbiont is discussed.