Lipidomics has been proving that membrane lipids play a crucial role in several cell functions and are involved in several pathologies, including cancer. In fact, beyond a scaffold where proteins and ...other components are embedded, the cell membrane can also act as a barrier or a target for anticancer drugs. From this point of view, the development of new chemotherapeutic agents should also take into account the role of the membrane in their activity. This Review aims to highlight the importance of anticancer drug-membrane interactions as a powerful strategy to improve cancer therapy. Biophysical techniques emerge, therefore, as essential tools to unveil such interactions.
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•Cancer cells present changes in phospholipid constitution, surface charge and membrane fluidity.•The structural, biophysical and functional differences between cancer and normal cell membranes can modulate drug activity.•Mimetic models have been developed to overcome membrane's complexity and used to study anticancer drug-membrane interactions.•Research of new cancer therapies using membrane biophysics may be a path to overcome the problems found in clinical practice.
Fraudulent milk adulteration is a dangerous practice in the dairy industry that is harmful to consumers since milk is one of the most consumed food products. Milk quality can be assessed by Fourier ...Transformed Infrared Spectroscopy (FTIR), a simple and fast method for obtaining its compositional information. The spectral data produced by this technique can be explored using machine learning methods, such as neural networks and decision trees, in order to create models that represent the characteristics of pure and adulterated milk samples.
Thousands of milk samples were collected, some of them were manually adulterated with five different substances and subjected to infrared spectroscopy. This technique produced spectral data from the milk samples composition, which were used for training different machine learning algorithms, such as deep and ensemble decision tree learners. The proposed method is used to predict the presence of adulterants in a binary classification problem and also the specific assessment of which of five adulterants was found through multiclass classification. In deep learning, we propose a Convolutional Neural Network architecture that needs no preprocessing on spectral data. Classifiers evaluated show promising results, with classification accuracies up to 98.76%, outperforming commonly used classical learning methods.
The proposed methodology uses machine learning techniques on milk spectral data. It is able to predict common adulterations that occur in the dairy industry. Both deep and ensemble tree learners were evaluated considering binary and multiclass classifications and the results were compared. The proposed neural network architecture is able to outperform the composition recognition made by the FTIR equipment and by commonly used methods in the dairy industry.
Peroxisomes are ubiquitous organelles with well-defined functions in lipid and reactive oxygen species metabolism, having a significant impact on a large number of important diseases. Growing ...evidence points to them, in concert with mitochondria, as important players within the antiviral response. In this review we summarize and discuss the recent findings concerning the relevance of peroxisomes within innate immunity. We not only emphasize their importance as platforms for cellular antiviral signaling but also review the current information concerning their role in the control of bacterial infections. We furthermore review the recent data that pinpoints peroxisomes as regulators of inflammatory processes.
Cheese whey addition to milk is a type of fraud with high prevalence and severe economic effects, resulting in low yield for dairy products, nutritional reduction of milk and milk-derived products, ...and even some safety concerns. Nevertheless, methods to detect fraudulent addition of cheese whey to milk are expensive and time consuming, and are thus ineffective as screening methods. The Fourier-transform infrared (FTIR) spectroscopy technique is a promising alternative to identify this type of fraud because a large number of data are generated, and useful information might be extracted to be used by machine learning models. The objective of this work was to evaluate the use of FTIR with machine learning methods, such as classification tree and multilayer perceptron neural networks to detect the addition of cheese whey to milk. A total of 520 samples of raw milk were added with cheese whey in concentrations of 1, 2, 5, 10, 15, 20, 25, and 30%; and 65 samples were used as control. The samples were stored at 7, 20, and 30°C for 0, 24, 48, 72, and 168 h, and analyzed using FTIR equipment. Complementary results of 520 samples of authentic raw milk were used. Selected components (fat, protein, casein, lactose, total solids, and solids nonfat) and freezing point (°C) were predicted using FTIR and then used as input features for the machine learning algorithms. Performance metrics included accuracy as high as 96.2% for CART (classification and regression trees) and 97.8% for multilayer perceptron neural networks, with precision, sensitivity, and specificity above 95% for both methods. The use of milk composition and freezing point predicted using FTIR, associated with machine learning techniques, was highly efficient to differentiate authentic milk from samples added with cheese whey. The results indicate that this is a potential method to be used as a high-performance screening process to detected milk adulterated with cheese whey in milk quality laboratories.
Diabetes mellitus (DM) is characterized by hyperglycaemia, resulting from defects in insulin secretion, insulin action or both. There are several factors such as hyperlipidemia and oxidative stress ...(OS), namely the production of reactive oxygen/nitrogen species (ROS/RNS), that actively contribute to the development and worsening of DM. Chalcones, also termed as benzalacetophenone or benzylidene acetophenone, present a 1,3-diaryl-2-propen-1-one scaffold that has been shown to be highly promising in the development of new antioxidant compounds. Considering the potential interest of antioxidant therapy, the present review scrutinizes the role of the main sources of ROS/RNS production during DM. The modulatory effect of chalcones against nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, xanthine oxidase, mitochondrial respiratory chain and nitric oxide synthase, is also thoroughly discussed, establishing, whenever possible, a structure-activity relationship (SAR). From the SAR analysis, it can be stated that the presence of catechol groups, hydroxyl and methoxyl substituents in the chalcones scaffold improves their modulatory activity against the main sources of ROS/RNS production in DM.
The aim of this study was to evaluate the risk factors associated with noncarious cervical lesions (NCCLs), cervical dentin hypersensitivity (CDH), and gingival recession (GR), besides the ...relationship among these conditions in a specific Brazilian sample population.
185 patients who attended the "Ambulatory Program for Rehabilitation of Patients with Noncarious Cervical Lesions and Cervical Dentin Hypersensitivity" were evaluated, and 5180 teeth were analyzed. The subjects filled out a form and a calibrated examiner performed the clinical exams to determine the presence of NCCLs, CDH, and GR. NCCLs were classified according to their morphology and depth, CDH levels were evaluated according to air stimuli response, and GRs were categorized according to Miller’s classification. The association of the risk factors with NCCLs, CDH, and GR was determined with the Mann-Whitney U test and multiple linear regression. For the correlations, the Spearman test was used with a 95%-confidence level.
The NCCLs, CDH, and GR distributions within the study were 88.1%, 89.1%, and 59.4%, respectively. Maxillary premolars were the most affected by all three conditions. A positive correlation was found between age, NCCLs, and GR; between NCCLs and CDH; CDH and GR; GR and NCCLs. Age, gender, oral hygiene, gastroesophageal diseases, and occlusal trauma were significantly associated with the presence of all three conditions.
The NCCLs and GR distributions increased with age; NCCLs, CDH, and GR had positive correlation; the lesions’ depth and morphology contributed to high levels of sensitivity and severity of recessions; age, gender, gastric disease, and occlusal trauma were relevant factors for the occurrence of NCCLs, CDH, and GR.
The increasing distribution of NCCLs, CDH, and GR is closely associated with people’s lifestyles. Thus, it is important for the clinicians to recognize the etiological factors and their most relevant associations to prevent and control such alterations, in order to improve the population’s quality of life.
Emerging evidence highlights the multifaceted roles of the RNA epitranscriptome during viral infections. By modulating the modification landscape of viral and host RNAs, viruses enhance their ...propagation and elude host surveillance mechanisms. Here, we discuss how specific RNA modifications, in either host or viral RNA molecules, impact the virus-life cycle and host antiviral responses, highlighting the potential of targeting the RNA epitranscriptome for novel antiviral therapies.
α-Glucosidase inhibitors are described as the most effective in reducing post-prandial hyperglycaemia (PPHG) from all available anti-diabetic drugs used in the management of type 2 diabetes mellitus. ...As flavonoids are promising modulators of this enzyme's activity, a panel of 44 flavonoids, organised in five groups, was screened for their inhibitory activity of α-glucosidase, based on in vitro structure-activity relationship studies. Inhibitory kinetic analysis and molecular docking calculations were also applied for selected compounds. A flavonoid with two catechol groups in A- and B-rings, together with a 3-OH group at C-ring, was the most active, presenting an IC
50
much lower than the one found for the most widely prescribed α-glucosidase inhibitor, acarbose. The present work suggests that several of the studied flavonoids have the potential to be used as alternatives for the regulation of PPHG.
Human papillomaviruses (HPV) are the causative agents of the most common sexually transmitted infection worldwide. While infection is generally asymptomatic and can be cleared by the host immune ...system, when persistence occurs, HPV can become a risk factor for malignant transformation. Progression to cancer is actually an unintended consequence of the complex HPV life cycle. Different antiviral defence mechanisms recognize HPV early in infection, leading to the activation of the innate immune response. However, the virus has evolved several specific strategies to efficiently evade the antiviral immune signalling. Here, we review and discuss the interplay between HPV and the host cell innate immunity. We further highlight the evasion strategies developed by different HPV to escape this cellular response and focus on the correlation with HPV-induced persistence and tumorigenesis.
Localization of mTORC2 activity inside cells Ebner, Michael; Sinkovics, Benjamin; Szczygieł, Magdalena ...
The Journal of cell biology,
02/2017, Volume:
216, Issue:
2
Journal Article
Peer reviewed
Open access
Activation of protein kinase Akt via its direct phosphorylation by mammalian target of rapamycin (mTOR) complex 2 (mTORC2) couples extracellular growth and survival cues with pathways controlling ...cell growth and proliferation, yet how growth factors target the activity of mTORC2 toward Akt is unknown. In this study, we examine the localization of the obligate mTORC2 component, mSin1, inside cells and report the development of a reporter to examine intracellular localization and regulation by growth factors of the endogenous mTORC2 activity. Using a combination of imaging and biochemical approaches, we demonstrate that inside cells, mTORC2 activity localizes to the plasma membrane, mitochondria, and a subpopulation of endosomal vesicles. We show that unlike the endosomal pool, the activity and localization of mTORC2 via the Sin1 pleckstrin homology domain at the plasma membrane is PI3K and growth factor independent. Furthermore, we show that membrane recruitment is sufficient for Akt phosphorylation in response to growth factors. Our results indicate the existence of spatially separated mTORC2 populations with distinct sensitivity to PI3K inside cells and suggest that intracellular localization could contribute to regulation of mTORC2 activity toward Akt.
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