Breast cancer is a complex disease which cannot be defined merely by clinical parameters like lymph node involvement and histological grade, or by routinely used biomarkers like estrogen receptor ...(ER), progesterone receptor (PGR) and epidermal growth factor receptor 2 (HER2) in diagnosis and prognosis. Breast cancer originates from the epithelial cells. Keratins (K) are cytoplasmic intermediate filament proteins of epithelial cells and changes in the expression pattern of keratins have been seen during malignant transformation in the breast. Expression of the K8/18 pair is seen in the luminal cells of the breast epithelium, and its role in prognostication of breast cancer is not well understood.
In this study, we have modulated K8 expression to understand the role of the K8/18 pair in three different breast epithelium derived cell lines: non-transformed MCF10A, transformed but poorly invasive MDA MB 468 and highly invasive MDA MB 435. The up-regulation of K8 in the invasive MDA MB 435 cell line resulted in a significant decrease in proliferation, motility, in-vitro invasion, tumor volume and lung metastasis. The down-regulation of K8 in MDA MB 468 resulted in a significant increase in transformation potential, motility and invasion in-vitro, while MCF10A did not show any changes in cell transformation assays.
These results indicate the role of K8/18 in modulating invasion in breast cancer -its presence correlating with less invasive phenotype and absence correlating with highly invasive, dedifferentiated phenotype. These data may have important implications for prognostication of breast cancer.
•High rate of photocatalysis under solar light.•Photocatalysis combining economical and sustainable components including TiO2, black volcanic ashes and solar light.•TiO2 nanoparticles loaded on a ...natural material (black volcanic ashes).•Catalyst can absorb both UV and visible light.•Photocatalyst in particles for eliminating the complex liquid/powder separation process for wastewater treatment.
Heterogeneous photocatalysis based on TiO2, as advanced oxidation process, has proven to be an effective application in the removal of aqueous and gaseous pollutants. The use of solar energy to degrade pollutants by photocatalysis represents an economic and sustainable alternative. This research focuses on the photodegradation of pollutants from wastewater by TiO2 nanostructured loaded into a natural mineral material (volcanic soil of black lava). The activity of the photocatalyst was evaluated in different conditions of radiation under sunlight. The results showed that the material is an efficient photocatalyst under visible light, obtaining 95% degradation of wastewater pollutant under sunlight irradiation after only 2h, and can be proposed for its use in photoreactors for treatment of high-volume of wastewater. The studied material can be used for advanced oxidation treatments in photoreaction systems with continuous flow, thereby resolving the problems arising from the use of conventional powder photocatalytic systems.
ABSTRACT
Aims As part of a larger study to estimate the global burden of disease and injury attributable to alcohol: to evaluate the evidence for a causal impact of average volume of alcohol ...consumption and pattern of drinking on diseases and injuries; to quantify relationships identified as causal based on published meta‐analyses; to separate the impact on mortality versus morbidity where possible; and to assess the impact of the quality of alcohol on burden of disease.
Methods Systematic literature reviews were used to identify alcohol‐related diseases, birth complications and injuries using standard epidemiological criteria to determine causality. The extent of the risk relations was taken from meta‐analyses.
Results Evidence of a causal impact of average volume of alcohol consumption was found for the following major diseases: tuberculosis, mouth, nasopharynx, other pharynx and oropharynx cancer, oesophageal cancer, colon and rectum cancer, liver cancer, female breast cancer, diabetes mellitus, alcohol use disorders, unipolar depressive disorders, epilepsy, hypertensive heart disease, ischaemic heart disease (IHD), ischaemic and haemorrhagic stroke, conduction disorders and other dysrhythmias, lower respiratory infections (pneumonia), cirrhosis of the liver, preterm birth complications and fetal alcohol syndrome. Dose–response relationships could be quantified for all disease categories except for depressive disorders, with the relative risk increasing with increased level of alcohol consumption for most diseases. Both average volume and drinking pattern were linked causally to IHD, fetal alcohol syndrome and unintentional and intentional injuries. For IHD, ischaemic stroke and diabetes mellitus beneficial effects were observed for patterns of light to moderate drinking without heavy drinking occasions (as defined by 60+ g pure alcohol per day). For several disease and injury categories, the effects were stronger on mortality compared to morbidity. There was insufficient evidence to establish whether quality of alcohol had a major impact on disease burden.
Conclusions Overall, these findings indicate that alcohol impacts many disease outcomes causally, both chronic and acute, and injuries. In addition, a pattern of heavy episodic drinking increases risk for some disease and all injury outcomes. Future studies need to address a number of methodological issues, especially the differential role of average volume versus drinking pattern, in order to obtain more accurate risk estimates and to understand more clearly the nature of alcohol–disease relationships.
Maternal consumption of a high-fat diet (HFD) during pregnancy and lactation is closely related to hepatic lipid accumulation, insulin resistance and increased serum cytokine levels in offspring and ...into their adulthood. MicroRNA (miRNA) have been implicated in cholesterol biosynthesis and fatty acid metabolism. We evaluated the modulation of hepatic fatty acid synthesis (de novo), β-oxidation pathways, and miRNA-122 (miR-122) and miRNA-370 (miR-370) expression in recently weaned offspring (day 28) of mouse dams fed a HFD (HFD-O) or a standard chow (SC-O) during pregnancy and lactation. Compared with SC-O mice, HFD-O mice weighed more, had a larger adipose tissue mass and were more intolerant to glucose and insulin (P< 0·05). HFD-O mice also presented more levels of serum cholesterol, TAG, NEFA and hepatic IκB kinase and c-Jun N-terminal kinase phosphorylation compared with SC-O mice (P< 0·05). Protein levels of fatty acid synthase, acetyl-CoA carboxylase and 3-hydroxy-3-methylglutaryl-CoA reductase were similar in HFD-O and SC-O mice, whereas expression levels of SCD1 mRNA and protein were more abundant in HFD-O mice than in SC-O mice (P< 0·05). Interestingly, mRNA expression levels of the β-oxidation-related genes ACADVL and CPT1 were decreased in HFD-O mice (P< 0·05). Furthermore, the expression of miR-122 was reduced but that of miR-370 was increased in HFD-O mice compared with that in SC-O mice (P< 0·05). Changes in hepatic lipid metabolism were accompanied by increased mRNA content of AGPAT1 and TAG deposition in HFD-O mice (P< 0·05). Taken together, the present results strongly suggest that maternal consumption of a HFD affects the early lipid metabolism of offspring by modulating the expression of hepatic β-oxidation-related genes and miRNA that can contribute to metabolic disturbances in adult life.
World Allergy Organization anaphylaxis guidelines: Summary Simons, F. Estelle R., MD, FRCPC; Ardusso, Ledit R.F., MD; Bilò, M. Beatrice, MD ...
Journal of allergy and clinical immunology,
03/2011, Letnik:
127, Številka:
3
Journal Article
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When indicated at any time during the episode, additional important steps include administering supplemental oxygen and maintaining the airway, establishing intravenous access and giving fluid ...resuscitation, and initiating cardiopulmonary resuscitation with continuous chest compressions before rescue breathing.\n Intravenous Chlorpheniramine or Diphenhydramine; Oral Cetirizine) Beta-2 Adrenergic Agonistsa (eg. Intravenous Hydrocortisone or Methylprednisolone; Oral Prednisone or Prednisolone) Strength of recommendation for use in anaphylaxisb C C C Pharmacologic effects At H1-receptor, inverse agonist effect; stabilize receptors in inactive conformation; decrease skin and mucosal symptoms At beta-2 receptor, increase bronchodilation Switch off transcription of activated genes that encode pro-inflammatory proteins; decrease late phase allergic response Clinical relevance Decrease itch, flush, urticaria, sneezing, and rhinorrhea, but are not life-saving because they do not prevent or relieve obstruction to airflow or hypotension/shock Decrease wheeze, cough and shortness of breath but are not life-saving because they do not prevent or relieve upper airway obstruction or hypotension/shock Onset of action takes several hours; therefore, are not life-saving in initial hours of an anaphylactic episode; used to prevent and relieve protracted or biphasic anaphylaxis; however, these effects have not been proven Potential adverse effects (usual dose) First-generation drugs cause drowsiness, somnolence, and impaired cognitive functionc Tremor, tachycardia, dizziness, jitteriness Unlikely during a short course Potential adverse effects (overdose) Extreme drowsiness, confusion, coma, respiratory depression, paradoxical central nervous system stimulation, eg. seizures in infants and children Headache, hypokalemia, vasodilation Unlikely Comment From 0 to 14 different H1-antihistamines,c and different dose regimens, are listed as adjunctive medications in anaphylaxis guidelines; role not proven Use in anaphylaxis is extrapolated from use in acute asthma; if given as adjunctive treatment for bronchospasm not relieved by epinephrine, should optimally be delivered by face mask and nebulization From 0 to 3 different glucocorticoids,d and different dose regimens,d are listed as adjunctive medications in anaphylaxis guidelines; role not proven Table 8 Second-Line Medications for Anaphylaxis Treatment Medication Epinephrine/adrenaline auto-injectora Epinephrine from an ampule/syringeb or prefilled syringec (alternative but not preferred formulations) Other aspects of discharge management Anaphylaxis emergency action plan (personalized, written) Medical identification (eg, bracelet, wallet card) Medical record electronic flag (or chart sticker) Emphasize the importance of follow-up, preferably with an allergy/immunology specialist Assessment of sensitization to allergen Before discharge, consider assessing sensitization to allergens suggested in the history of the acute episode, by measuring serum IgE levels to relevant allergen(s), if the test is availabled 3-4 weeks after the episode, confirm allergen sensitization using skin testse Challenge/provocation tests might be needed in some patients, for example, with food or medication allergy, in order to assess risk of future anaphylactic episodes furtherf Long-term risk reduction: avoidance and/or immunomodulation Food-triggered anaphylaxis: avoidance of relevant food(s) Stinging insect-triggered anaphylaxis: avoidance of stinging insects; subcutaneous venom immunotherapy (protects up to 80-90% of adults and 98% of children) Medication-triggered anaphylaxis: avoidance of relevant medications; if indicated, medically supervised desensitization in a healthcare setting according to published protocols Idiopathic anaphylaxis: for frequent episodes, consider glucocorticoid and H1-antihistamine prophylaxis for 2-3 months Optimal management of asthma and other concomitant diseases Table 9 Recommendations at Time of Discharge From the Healthcare Setting
International Consensus on drug allergy Demoly, P.; Adkinson, N. F.; Brockow, K. ...
Allergy,
April 2014, Letnik:
69, Številka:
4
Journal Article, Conference Proceeding
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When drug reactions resembling allergy occur, they are called drug hypersensitivity reactions (DHRs) before showing the evidence of either drug‐specific antibodies or T cells. DHRs may be allergic or ...nonallergic in nature, with drug allergies being immunologically mediated DHRs. These reactions are typically unpredictable. They can be life‐threatening, may require or prolong hospitalization, and may necessitate changes in subsequent therapy. Both underdiagnosis (due to under‐reporting) and overdiagnosis (due to an overuse of the term ‘allergy’) are common. A definitive diagnosis of such reactions is required in order to institute adequate treatment options and proper preventive measures. Misclassification based solely on the DHR history without further testing may affect treatment options, result in adverse consequences, and lead to the use of more‐expensive or less‐effective drugs, in contrast to patients who had undergone a complete drug allergy workup. Several guidelines and/or consensus documents on general or specific drug class‐induced DHRs are available to support the medical decision process. The use of standardized systematic approaches for the diagnosis and management of DHRs carries the potential to improve outcomes and should thus be disseminated and implemented. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), and the World Allergy Organization (WAO), has decided to issue an International CONsensus (ICON) on drug allergy. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences and deficiencies of evidence, thus providing a comprehensive reference document for the diagnosis and management of DHRs.
Open-cell foams based on hydroxyapatite (HAp) can mimic the extracellular matrix (ECM) to better replace damaged hard tissues and assist in their regeneration processes. Aerogels of HAp nanowires ...(NW) with barium titanate (BT) particles were produced and characterized regarding their physical and chemical properties, bioactivity, and in vitro cytotoxicity. Considering the role of piezoelectricity (mainly due to collagen) and surface charges in bone remodeling, all BT particles, of size 280 nm and 2 and 3 µm, contained BaTiO
in their piezoelectric tetragonal phase. The synthesized nanowires were verified to be AB-type carbonated hydroxyapatite. The aerogels showed high porosity and relatively homogeneous distribution of the BT particles. Barium titanate proved to be non-cytotoxic while all the aerogels produced were cytotoxic for an extract concentration of 1 mg/mL but became non-cytotoxic at concentrations of 0.5 mg/mL and below. It is possible that these results were affected by the higher surface area and quicker dissolution rate of the aerogels. In the bioactivity assays, SEM/EDS, it was not easy to differentiate between the apatite deposition and the surface of the HAp wires. However, a quantitative EDS analysis shows a possible CaP deposition/dissolution cycle taking place.
ABSTRACT
The general dynamic model of oceanic island biogeography (GDM) has added a new dimension to theoretical island biogeography in recognizing that geological processes are key drivers of the ...evolutionary processes of diversification and extinction within remote islands. It provides a dynamic and essentially non‐equilibrium framework generating novel predictions for emergent diversity properties of oceanic islands and archipelagos. Its publication in 2008 coincided with, and spurred on, renewed attention to the dynamics of remote islands. We review progress, both in testing the GDM's predictions and in developing and enhancing ecological–evolutionary understanding of oceanic island systems through the lens of the GDM. In particular, we focus on four main themes: (i) macroecological tests using a space‐for‐time rationale; (ii) extensions of theory to islands following different patterns of ontogeny; (iii) the implications of GDM dynamics for lineage diversification and trait evolution; and (iv) the potential for downscaling GDM dynamics to local‐scale ecological patterns and processes within islands. We also consider the implications of the GDM for understanding patterns of non‐native species diversity. We demonstrate the vitality of the field of island biogeography by identifying a range of potentially productive lines for future research.
Management and treatment of chronic urticaria (CU) Maurer, M.; Church, M.K.; Gonçalo, M. ...
JEADV. Journal of the European Academy of Dermatology and Venereology/Journal of the European Academy of Dermatology and Venereology,
06/2015, Letnik:
29, Številka:
S3
Journal Article
Recenzirano
Odprti dostop
Developments increasing our understanding of chronic urticaria have resulted in the simplification and improvement of available treatments. Currently, many treatments target mast cell mediators, but ...we can now disrupt mast cell activation with the anti‐IgE antibody omalizumab, which has markedly advanced the treatment landscape for patients with difficult‐to‐treat urticaria. Current guidelines provide a framework for the management and treatment of patients with CU but, as each patient is different, knowledge and experience of specialist dermatologists and allergists are key to effective pharmacotherapy. This article reviews the different therapeutic options for patients with chronic spontaneous urticaria (also called chronic idiopathic urticaria) or chronic inducible urticaria and discusses management of special populations or special circumstances related to CU.
Bottom‐up tissue engineering is a promising approach for designing modular biomimetic structures that aim to recapitulate the intricate hierarchy and biofunctionality of native human tissues. In ...recent years, this field has seen exciting progress driven by an increasing knowledge of biological systems and their rational deconstruction into key core components. Relevant advances in the bottom‐up assembly of unitary living blocks toward the creation of higher order bioarchitectures based on multicellular‐rich structures or multicomponent cell–biomaterial synergies are described. An up‐to‐date critical overview of long‐term existing and rapidly emerging technologies for integrative bottom‐up tissue engineering is provided, including discussion of their practical challenges and required advances. It is envisioned that a combination of cell–biomaterial constructs with bioadaptable features and biospecific 3D designs will contribute to the development of more robust and functional humanized tissues for therapies and disease models, as well as tools for fundamental biological studies.
The recapitulation of native tissue hierarchy and biofunctionality remains a remarkable challenge. Bottom‐up tissue engineering has arisen as the most promising approach for designing modular biomimetic 3D microtissues that can better display the biofunctionality and biospecific design of living architectures. The most recent advances in integrative bottom‐up engineering of functional microtissues are discussed.
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