Mechanistic insights into the release of doxorubicin from graphene oxide in cancer cells

Liposomal doxorubicin (L-DOX) is a popular drug formulation for the treatment of several cancer types (e.g., recurrent ovarian cancer, metastatic breast cancer, multiple myeloma, etc.), but poor nuclear internalization has hampered its clinical applicability so far. Therefore, novel drug-delivery nanosystems are actively researched in cancer chemotherapy. Here we demonstrate that DOX-loaded graphene oxide (GO), GO-DOX, exhibits much higher anticancer efficacy as compared to its L-DOX counterpart if administered to cellular models of breast cancer. Then, by a combination of live-cell confocal imaging and fluorescence lifetime imaging microscopy (FLIM), we suggest that GO-DOX may realize its superior performances by inducing massive intracellular DOX release (and its subsequent nuclear accumulation) upon binding to the cell plasma membrane. Reported results lay the foundation for future exploitation of these new adducts as high-performance nanochemotherapeutic agents

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.Fil: Di Santo, Mariana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Alaimo, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Domínguez Rubio, Ana Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Pérez, Oscar E.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentin

Disentangling EEG responses to TMS due to cortical and peripheral activations

Background: the use of combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) for the functional evaluation of the cerebral cortex in health and disease is becoming increasingly common. However, there is still some ambiguity regarding the extent to which brain responses to auditory and somatosensory stimulation contribute to the TMS-evoked potential (TEP). Objective/Hypothesis: to measure separately the contribution of auditory and somatosensory stimulation caused by TMS, and to assess their contribution to the TEP waveform, when stimulating the motor cortex (M1). Methods: 19 healthy volunteers underwent 7 blocks of EEG recording. To assess the impact of auditory stimulation on the TEP waveform, we used a standard figure of eight coil, with or without masking with a continuous noise reproducing the specific time-varying frequencies of the TMS click, stimulating at 90% of resting motor threshold. To further characterise auditory responses due to the TMS click, we used either a standard or a sham figure of eight coil placed on a pasteboard cylinder that rested on the scalp, with or without masking. Lastly, we used electrical stimulation of the scalp to investigate the possible contribution of somatosensory activation. Results: auditory stimulation induced a known pattern of responses in electrodes located around the vertex, which could be suppressed by appropriate noise masking. Electrical stimulation of the scalp alone only induced similar, non-specific scalp responses in the in the central electrodes. TMS, coupled with appropriate masking of sensory input, resulted in specific, lateralized responses at the stimulation site, lasting around 300 ms. Conclusions: if careful control of confounding sources is applied, TMS over M1 can generate genuine, lateralized EEG activity. By contrast, sensory evoked responses, if present, are represented by non-specific, late (100–200 ms) components, located at the vertex, possibly due to saliency of the stimuli. Notably, the latter can confound the TEP if masking procedures are not properly used

Disentangling EEG responses to TMS due to cortical and peripheral activations

BACKGROUND: the use of combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) for the functional evaluation of the cerebral cortex in health and disease is becoming increasingly common. However, there is still some ambiguity regarding the extent to which brain responses to auditory and somatosensory stimulation contribute to the TMS-evoked potential (TEP). OBJECTIVE/HYPOTHESIS: to measure separately the contribution of auditory and somatosensory stimulation caused by TMS, and to assess their contribution to the TEP waveform, when stimulating the motor cortex (M1). METHODS: 19 healthy volunteers underwent 7 blocks of EEG recording. To assess the impact of auditory stimulation on the TEP waveform, we used a standard figure of eight coil, with or without masking with a continuous noise reproducing the specific time-varying frequencies of the TMS click, stimulating at 90% of resting motor threshold. To further characterise auditory responses due to the TMS click, we used either a standard or a sham figure of eight coil placed on a pasteboard cylinder that rested on the scalp, with or without masking. Lastly, we used electrical stimulation of the scalp to investigate the possible contribution of somatosensory activation. RESULTS: auditory stimulation induced a known pattern of responses in electrodes located around the vertex, which could be suppressed by appropriate noise masking. Electrical stimulation of the scalp alone only induced similar, non-specific scalp responses in the in the central electrodes. TMS, coupled with appropriate masking of sensory input, resulted in specific, lateralized responses at the stimulation site, lasting around 300 ms. CONCLUSIONS: if careful control of confounding sources is applied, TMS over M1 can generate genuine, lateralized EEG activity. By contrast, sensory evoked responses, if present, are represented by non-specific, late (100-200 ms) components, located at the vertex, possibly due to saliency of the stimuli. Notably, the latter can confound the TEP if masking procedures are not properly used

Percutaneous tibial nerve stimulation (PTNS) efficacy in the treatment of lower urinary tract dysfunctions. A systematic review

Background: Percutaneous Tibial Nerve Stimulation (PTNS) has been proposed for the treatment of overactive bladder syndrome (OAB), non-obstructive urinary retention (NOUR), neurogenic bladder, paediatric voiding dysfunction and chronic pelvic pain/painful bladder syndrome (CPP/PBS). Despite a number of publications produced in the last ten years, the role of PTNS in urinary tract dysfunctions remains unclear. A systematic review of the papers on PTNS has been performed with the aim to better clarify potentialities and limits of this technique in the treatment of OAB syndrome and in other above mentioned urological conditions. Methods. A literature search using MEDLINE and ISI web was performed. Search terms used were "tibial nerve" and each of the already mentioned conditions, with no time limits. An evaluation of level of evidence for each paper was performed. Results: PTNS was found to be effective in 37-100% of patients with OAB, in 41-100% of patients with NOUR and in up to 100% of patients with CPP/PBS, children with OAB/dysfunctional voiding and patients with neurogenic pathologies. No major complications have been reported.Randomized controlled trials are available only for OAB (4 studies) and CPP/PBS (2 studies). Level 1 evidence of PTNS efficacy for OAB is available. Promising results, to be confirmed by randomized controlled studies, have been obtained in the remaining indications considered. Conclusions: PTNS is an effective and safe option to treat OAB patients. Further studies are needed to assess the role of PTNS in the remaining indications and to evaluate the long term durability of the treatment. Further research is needed to address several unanswered questions about PTNS

Carrageenan-induced acute inflammation in the mouse air pouch synovial model. Role of tumour necrosis factor

We used the mouse air pouch model of inflammation to study the interaction between cytokines, prostaglandin E2 (PGE2) and cell migration during the various phases of acute local inflammation induced by carrageenan. In serum, the levels of interleukin 1 (IL-1), interleukin 6 (IL-6), tumour necrosis factor (TNF), serum amiloid-A (SAA) and Fe++ were never different from controls, indicating that no systemic inflammatory changes were induced. Locally the exudate volume and the number of leukocytes recruited into the pouch increased progressively until 7 days after carrageenan. The same was true for PGE2 production. We could not measure IL-1 but the production of IL-6 and TNF reached a maximum after 5-24 h then quickly decreased. Anti-TNF antibodies inhibited cell migration by 50% 24 h after treatment. Pretreatment with interleukin 10 (IL-10) inhibited TNF production almost completely and cell migration by 60%. Carrageenan-induced inflammation was modulated by anti-inflammatory drugs. Pretreatment with dexamethasone (DEX) or indomethacin (INDO) inhibited cell migration and reduced the concentration of TNF in the exudate. Production of PGE2 or vascular permeability did not correlate with the number of cells in the pouch. Local TNF seems to play an important role in this model, particularly for leukocyte migration in the first phase of the inflammatory process. In conclusion, the air pouch seems to be a good model for studying the regulation of the early events of local inflammation, particularly the role of cytokines and cell migration

Ni Catalysts Supported Over TiO2, SiO2 and ZrO2 for the Steam Reforming of Glycerol

A 72-year-old man was admitted with one blade of a huge pair of shears in his left thorax. His hemodynamics deteriorated due to life-threatening vascular lesions. An urgent thoracotomy revealed several injuries to the intercostal vessels and left apical inferior lung lobe. The blade tip was stuck in the posterior chest wall, 2 cm adjacent to the descending aorta. The blade was removed, the lung was sutured, and the patient made a good recovery

Ni Catalysts Supported Over TiO2, SiO2 and ZrO2 for the Steam Reforming of Glycerol

Ni-based catalysts supported on TiO2, ZrO2 and SiO2 (in the form of mesoporous Santa Barbara Amorphous 15 (SBA-15) and amorphous dense nanoparticles), were employed in the steam reforming of glycerol. Each sample was prepared by liquid phase synthesis of the support followed by impregnation with the active phase and calcination at 8008C or by direct synthesis through flame pyrolysis. Many techniques have been used to assess the physical chemical properties of both the fresh and spent catalysts, such as atomic absorption, N2 adsorption/desorption, XRD, SEM, TEM, temperature-programmed reduction (TPR), X-ray photoelectron spectroscopy (XPS), Micro-Raman and FTIR spectroscopy. The samples showed different textural, structural and morphological properties,as well as different reducibility and thermal resistance depending on the preparation method and support. Some of these properties were tightly bound to catalyst performance, in terms of H2 productivity and stability towards coking and sintering. A key parameter was the metal\u2013support interaction, which strongly depended on the preparation procedure. In particular, the stronger the interaction, the more stable the metallic Ni clusters, which in turn lead to a higher catalytic activity and stability. Surface acidity was also taken into account, in which the nature of the acid sites was differentiated (silanols, titanols or Lewis acid sites). The characterisation of the spent catalysts also allowed us to interpret the deactivation process. The formation of multi-walled nanotubes was observed for every sample, though it was only in some cases that this led to severe deactivatio