Ιατρικά Άρθρα Αλέξανδρος Γ. Σφακιανάκης

Τρίτη 19 Δεκεμβρίου 2017

The Sangar Institute and personalised genomics

Julia Wilson talks to ecancer at EAPM 2017 in Belfast. She discusses the importance of genomic data in personalised medicine and some of the challenges involves. She highlights the exciting upcoming work in the Sangar Institute.

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Targeting Neuroinflammation to Treat Alzheimer’s Disease

Abstract

Over the past few decades, research on Alzheimer’s disease (AD) has focused on pathomechanisms linked to two of the major pathological hallmarks of extracellular deposition of beta-amyloid peptides and intra-neuronal formation of neurofibrils. Recently, a third disease component, the neuroinflammatory reaction mediated by cerebral innate immune cells, has entered the spotlight, prompted by findings from genetic, pre-clinical, and clinical studies. Various proteins that arise during neurodegeneration, including beta-amyloid, tau, heat shock proteins, and chromogranin, among others, act as danger-associated molecular patterns, that—upon engagement of pattern recognition receptors—induce inflammatory signaling pathways and ultimately lead to the production and release of immune mediators. These may have beneficial effects but ultimately compromise neuronal function and cause cell death. The current review, assembled by participants of the Chiclana Summer School on Neuroinflammation 2016, provides an overview of our current understanding of AD-related immune processes. We describe the principal cellular and molecular players in inflammation as they pertain to AD, examine modifying factors, and discuss potential future therapeutic targets.

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Increased anti-biofilm efficacy of toluidine blue on Staphylococcus species after nano-encapsulation.

Increased anti-biofilm efficacy of toluidine blue on Staphylococcus species after nano-encapsulation.

Photodiagnosis Photodyn Ther. 2017 Dec 13;:

Authors: Rout B, Liu CH, Wu WC

Abstract
BACKGROUND: Photodynamic therapy has been studied by many studies as a method for inactivating bacterial growth. Workers have used planktonic bacterial as well as biofilm bacterial cultures to evaluate the potential of photodynamic therapy in inactivating bacteria. However, almost all the studies use a photosensitiser in aqueous solution, which could be detrimental to the efficiency of photodynamic therapy.
METHODS: In this study, the photodynamic killing effect of toluidine blue O (TBO) has been investigated on Staphylococcal biofilms in -vitro. The sensitivity of the in-vitro biofilms to photodynamic killing action was compared using different formulations of TBO, different dosages of photosensitiser and different light irradiation strengths. Effect of TBO formulations on bacterial quorum sensing system was evaluated using a colorimetric assay. Finally, dual staining using hoechst and propidium iodide stains was carried out on the photodynamically treated biofilms to visualise and compare the effects of photodynamic therapy. Scanning electron microscope imagery was also carried out to evaluate the photodynamic killing effect on the in-vitro biofilms.
RESULTS: The sensitivity of biofilms to the photodynamic killing effect increased proportionally with the photosensitiser dosage and the light irradiation duration. TBO encapsulated in microemulsion was more effective in killing the biofilm bacteria than only TBO in water. The combination of TBO in microemulsion with EDTA was another effective way of increasing the photodynamic killing effect on the bacterial biofilms. Effect of encapsulated TBO on the quorum sensing system of bacteria was greater than the effect of aqueous solution of TBO. The in-vitro Staphylococcal biofilms could thus be inhibited by the photodynamic effect, and TBO encapsulated in microemulsion was much more effective than only TBO in water.
CONCLUSIONS: The encapsulation of a photosensitiser is an effective way of increasing the likelihood of the complete and successful inactivation of the biofilm growth. The encapsulated photosensitiser achieves higher inactivation of the bacterial biofilm than that of the aqueous solution of a photosensitiser.

PMID: 29247704 [PubMed - as supplied by publisher]

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Functional dissection of astrocyte-secreted proteins: Implications in brain health and diseases.

Functional dissection of astrocyte-secreted proteins: Implications in brain health and diseases.

Prog Neurobiol. 2017 Dec 13;:

Authors: Jha MK, Kim JH, Song GJ, Lee WH, Lee IK, Lee HW, An SSA, Kim S, Suk K

Abstract
Astrocytes, which are homeostatic cells of the central nervous system (CNS), display remarkable heterogeneity in their morphology and function. Besides their physical and metabolic support to neurons, astrocytes modulate the blood-brain barrier, regulate CNS synaptogenesis, guide axon pathfinding, maintain brain homeostasis, affect neuronal development and plasticity, and contribute to diverse neuropathologies via secreted proteins. The identification of astrocytic proteome and secretome profiles has provided new insights into the maintenance of neuronal health and survival, the pathogenesis of brain injury, and neurodegeneration. Recent advances in proteomics research have provided an excellent catalog of astrocyte-secreted proteins. This review categorizes astrocyte-secreted proteins and discusses evidence that astrocytes play a crucial role in neuronal activity and brain function. An in-depth understanding of astrocyte-secreted proteins and their pathways is pivotal for the development of novel strategies for restoring brain homeostasis, limiting brain injury/inflammation, counteracting neurodegeneration, and obtaining functional recovery.

PMID: 29247683 [PubMed - as supplied by publisher]

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Prospects and progress in the production of valuable carotenoids: insights from metabolic engineering, synthetic biology, and computational approaches.

Prospects and progress in the production of valuable carotenoids: insights from metabolic engineering, synthetic biology, and computational approaches.

J Biotechnol. 2017 Dec 13;:

Authors: Sankari M, Rao PR, Hemachandran H, Pullela PK, Doss C GP, Tayubi IA, Subramanian B, Gothandam KM, Singh P, Ramamoorthy S

Abstract
Carotenoids are isoprenoid pigments synthesized exclusively by plants and microorganisms and play critical roles in light harvesting, photoprotection, attracting pollinators and phytohormone production. In recent years, carotenoids have been used for their health benefits due to their high antioxidant activity and are extensively utilized in food, pharmaceutical, and nutraceutical industries. Regulation of carotenoid biosynthesis occurs throughout the life cycle of plants, with vibrant changes in composition based on developmental needs and responses to external environmental stimuli. With advancements in metabolic engineering techniques, there has been tremendous progress in the production of industrially valuable secondary metabolites such as carotenoids. Application of metabolic engineering and synthetic biology has become essential for the successful and improved production of carotenoids. Synthetic biology is an emerging discipline; metabolic engineering approaches may provide insights into novel ideas for biosynthetic pathways. In this review, we discuss the current knowledge on carotenoid biosynthetic pathways and genetic engineering of carotenoids to improve their nutritional value. In addition, we investigated synthetic biological approaches for the production of carotenoids. Theoretical biology approaches that may aid in understanding the biological sciences are discussed in this review. A combination of theoretical knowledge and experimental strategies may improve the production of industrially relevant secondary metabolites.

PMID: 29247672 [PubMed - as supplied by publisher]

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Combination of melatonin and rapamycin for head and neck cancer therapy: Suppression of AKT/mTOR pathway activation, and activation of mitophagy and apoptosis via mitochondrial function regulation.

Combination of melatonin and rapamycin for head and neck cancer therapy: Suppression of AKT/mTOR pathway activation, and activation of mitophagy and apoptosis via mitochondrial function regulation.

J Pineal Res. 2017 Dec 16;:

Authors: Shen YQ, Guerra-Librero A, Fernandez-Gil BI, Florido J, García-López S, Martinez-Ruiz L, Mendivil-Perez M, Soto-Mercado V, Acuña-Castroviejo D, Ortega-Arellano H, Carriel V, Diaz-Casado ME, Reiter RJ, Rusanova I, Nieto A, López LC, Escames G

Abstract
Head and neck squamous cell carcinoma (HNSCC) clearly involves activation of the Akt mammalian target of rapamycin (mTOR) signalling pathway. However, the effectiveness of treatment with the mTOR inhibitor rapamycin is often limited by chemoresistance. Melatonin suppresses neoplastic growth via different mechanisms in a variety of tumours. In the present study, we aimed to elucidate the effects of melatonin on rapamycin-induced HNSCC cell death, and to identify potential cross-talk pathways. We analysed the dose-dependent effects of melatonin in rapamycin-treated HNSCC cell lines (Cal-27 and SCC-9). These cells were treated with 0.1, 0.5, or 1 mM melatonin combined with 20 nM rapamycin. We further examined the potential synergistic effects of melatonin with rapamycin in Cal-27 xenograft mice. Relationships between inhibition of the mTOR pathway, reactive oxygen species (ROS), and apoptosis and mitophagy reportedly increased the cytotoxic effects of rapamycin in HNSCC. Our results demonstrated that combined treatment with rapamycin and melatonin blocked the negative feedback loop from the specific downstream effector of mTOR activation S6K1 to Akt signalling, which decreased cell viability, proliferation, and clonogenic capacity. Interestingly, combined treatment with rapamycin and melatonin induced changes in mitochondrial function, which were associated with increased ROS production, increasing apoptosis and mitophagy. This led to increase cell death and cellular differentiation. Our data further indicated that melatonin administration reduced rapamycin-associated toxicity to healthy cells. Overall, our findings suggested that melatonin could be used as an adjuvant agent with rapamycin, improving effectiveness while minimizing its side effects. This article is protected by copyright. All rights reserved.

PMID: 29247557 [PubMed - as supplied by publisher]

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Exploring the clinical use of ultrasound imaging: A survey of physiotherapists in New Zealand.

Exploring the clinical use of ultrasound imaging: A survey of physiotherapists in New Zealand.

Musculoskelet Sci Pract. 2017 Dec 08;34:27-37

Authors: Ellis R, De Jong R, Bassett S, Helsby J, Stokes M, Cairns M

Abstract
BACKGROUND: In New Zealand ultrasound imaging (USI) is being used increasingly by physiotherapists. To fully understand the extent to which physiotherapists in New Zealand are using USI, it is necessary to evaluate not only the context of its clinical use but also the barriers preventing its uptake.
OBJECTIVES: To examine the field and scope of use of USI, the type and content of training and the barriers restricting physiotherapists from using the technique.
DESIGN: Cross-sectional observational design utilising an Internet-based electronic survey.
METHOD: An electronic survey built on the design of previous research with guidance from an expert review panel. Participants were included if they were New Zealand registered physiotherapists.
RESULTS: Of the 465 participants who responded, 433 were eligible to complete the survey. There were 415 participants who completed the survey, 24% who said they used USI whilst 76% did not. For those using USI, the uses were varied including those within a rehabilitative paradigm (i.e. biofeedback; 52%) and also diagnostic (49%). USI training was also varied ranging from formal to informal. The main barriers preventing physiotherapists from using USI were lack of training, access to equipment, and equipment expense.
CONCLUSIONS: The participants reported a variety of clinical uses of USI and levels of training. A better understanding of the clinical uses and benefits of USI would enhance both training and clinical uptake. With the identification of barriers limiting physiotherapists' use of USI, ways to overcome these in New Zealand can now be explored further.

PMID: 29247981 [PubMed - as supplied by publisher]

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