Biological Activity of NHC-Gold-Alkynyl Complexes Derived from 3-Hydroxyflavones.

In this paper we describe the synthesis of new N-heterocyclic carbene (NHC) gold(I) derivatives with flavone-derived ligands with a propargyl ether group. The compounds were screened for their antimicrobial and anticancer activities, showing greater activity against bacteria than against colon cancer cells (Caco-2). Complexes [Au(L2b)(IMe)] (1b) and [Au(L2b)(IPr)] (2b) were found to be active against both Gram-positive and Gram-negative strains. The mechanism of action of 1b was evaluated by measurement of thioredoxin reductase (TrxR) and dihydrofolate reductase (DHFR) activity, besides scanning electron microscopy (SEM). Inhibition of the enzyme thioredoxin reductase is not observed in either Escherichia Coli or Caco-2 cells; however, DHFR activity is compromised after incubation of E. coli cells with complex 1b. Moreover, loss of structural integrity and change in bacterial shape is observed in the images obtained from scanning electron microscopy (SEM) after treatment E. coli cells with complex 1b.

Sulfonamide-Derived Dithiocarbamate Gold(I) Complexes Induce the Apoptosis of Colon Cancer Cells by the Activation of Caspase 3 and Redox Imbalance.

Two new families of dithiocarbamate gold(I) complexes derived from benzenesulfonamide with phosphine or carbene as ancillary ligands have been synthesized and characterized. In the screening of their in vitro activity on human colon carcinoma cells (Caco-2), we found that the more lipophilic complexes-those with the phosphine PPh3-exhibited the highest anticancer activity whilst also displaying significant cancer cell selectivity. [Au(S2CNHSO2C6H5)(PPh3)] (1) and [Au(S2CNHSO2-p-Me-C6H4)(IMePropargyl)] (8) produce cell death, probably by intrinsic apoptosis (mitochondrial membrane potential modification) and caspase 3 activation, causing cell cycle arrest in the G1 phase with p53 activation. Besides this, both complexes might act as multi-target anticancer drugs, as they inhibit the activity of the enzymes thioredoxin reductase (TrxR) and carbonic anhydrase (CA IX) with the alteration of the redox balance, and show a pro-oxidant effect.

Unveiling the Antioxidant Therapeutic Functionality of Sustainable Olive Pomace Active Ingredients.

Olive pomace (OP) is the main residue that results from olive oil production. OP is rich in bioactive compounds, including polyphenols, so its use in the treatments of diseases related to oxidative stress, such as cancer, could be considered. The present work aimed to study the biological properties of different OP extracts, obtained by ohmic heating-assisted extraction and conventional heating, using water and 50% ethanol, in the treatment and prevention of colorectal cancer through Caco-2 cell models. Additionally, an in-silico analysis was performed to identify the phenolic intestinal absorption and Caco-2 permeability. The extracts were chemically characterized, and it was found that the Ohmic-hydroethanolic (OH-EtOH) extract had the highest antiproliferative effect, probably due to its higher content of phenolic compounds. The OH-EtOH induced potential modifications in the mitochondrial membrane and led to apoptosis by cell cycle arrest in the G1/S phases with activation of p53 and caspase 3 proteins. In addition, this extract protected the intestine against oxidative stress (ROS) caused by H2O2. Therefore, the bioactive compounds present in OP and recovered by applying a green technology such as ohmic-heating, show promising potential to be used in food, nutraceutical, and biomedical applications, reducing this waste and facilitating the circular economy.

Gold(I) Complexes Bearing Alkylated 1,3,5-Triaza-7-phosphaadamantane Ligands as Thermoresponsive Anticancer Agents in Human Colon Cells.

Overheating can affect solubility or lipophilicity, among other properties, of some anticancer drugs. These temperature-dependent changes can improve efficiency and selectivity of the drugs, since they may affect their bioavailability, diffusion through cell membrane or activity. One recent approach to create thermosensitive molecules is the incorporation of fluorine atoms in the chemical structure, since fluor can tune some chemical properties such as binding affinity. Herein we report the anticancer effect of gold derivatives with phosphanes derived from 1,3,5-triaza-7-phosphaadamantane (PTA) with long hydrocarbon chains and the homologous fluorinated chains. Besides, we analysed the influence of temperature in the cytotoxic effect. The studied gold(I) complexes with phosphanes derived from PTA showed antiproliferative effect on human colon carcinoma cells (Caco-2/TC7 cell line), probably by inhibiting cellular TrxR causing a dysfunction in the intracellular redox state. In addition, the cell cycle was altered by the activation of p53, and the complexes produce apoptosis through mitochondrial depolarization and the consequent activation of caspase-3. Furthermore, the results suggest that this cytotoxic effect is enhanced by hyperthermia and the presence of polyfluorinated chains.

Phenolic-Rich Extracts from Avocado Fruit Residues as Functional Food Ingredients with Antioxidant and Antiproliferative Properties.

In this study, the total phenolic compounds content and profile, the nutritional value, the antioxidant and antiproliferative activities of avocado peel, seed coat, and seed extracts were characterized. Additionally, an in-silico analysis was performed to identify the phenolic compounds with the highest intestinal absorption and Caco-2 permeability. The avocado peel extract possessed the highest content of phenolic compounds (309.95 ± 25.33 mMol GA/100 g of extract) and the lowest effective concentration (EC50) against DPPH and ABTS radicals (72.64 ± 10.70 and 181.68 ± 18.47, respectively). On the other hand, the peel and seed coat extracts had the lowest energy densities (226.06 ± 0.06 kcal/100 g and 219.62 ± 0.49 kcal/100 g, respectively). Regarding the antiproliferative activity, the avocado peel extract (180 ± 40 µg/mL) showed the lowest inhibitory concentration (IC50), followed by the seed (200 ± 21 µg/mL) and seed coat (340 ± 32 µg/mL) extracts. The IC50 of the extracts induced apoptosis in Caco-2 cells at the early and late stages. According to the in-silico analysis, these results could be related to the higher Caco-2 permeability to hydroxysalidroside, salidroside, sakuranetin, and luteolin. Therefore, this study provides new insights regarding the potential use of these extracts as functional ingredients with antioxidant and antiproliferative properties and as medicinal agents in diseases related to oxidative stress such as cancer.

Grape Stem Extracts with Potential Anticancer and Antioxidant Properties.

The application of plant extracts for therapeutic purposes has been used in traditional medicine because plants contain bioactive compounds with beneficial properties for health. Currently, the use of these compounds that are rich in polyphenols for the treatment and prevention of diseases such as cancer, diabetes, and cardiovascular diseases, many of them related to oxidative stress, is gaining certain relevance. Polyphenols have been shown to have antimutagenic, antioxidant, and anti-inflammatory properties. Therefore, the objective of the present work was to study the potential effect of grape stem extracts (GSE), rich in phenolic compounds, in the treatment of cancer, as well as their role in the prevention of this disease associated with its antioxidant power. For that purpose, three cancer lines (Caco-2, MCF-7, and MDA-MB-231) were used, and the results showed that grape stem extracts were capable of showing an antiproliferative effect in these cells through apoptosis cell death associated with a modification of the mitochondrial potential and reactive oxygen species (ROS) levels. Additionally, grape stem extracts showed an antioxidant effect on differentiated intestinal cells that could protect the intestine from diseases related to oxidative stress. Therefore, grape extracts contain bioactive principles with important biological properties and could be used as bio-functional food ingredients to prevent diseases or even to improve certain aspects of human health.

DOLARS, a Distributed On-Line Activity Recognition System by Means of Heterogeneous Sensors in Real-Life Deployments-A Case Study in the Smart Lab of The University of Almería.

Activity Recognition (AR) is an active research topic focused on detecting human actions and behaviours in smart environments. In this work, we present the on-line activity recognition platform DOLARS (Distributed On-line Activity Recognition System) where data from heterogeneous sensors are evaluated in real time, including binary, wearable and location sensors. Different descriptors and metrics from the heterogeneous sensor data are integrated in a common feature vector whose extraction is developed by a sliding window approach under real-time conditions. DOLARS provides a distributed architecture where: (i) stages for processing data in AR are deployed in distributed nodes, (ii) temporal cache modules compute metrics which aggregate sensor data for computing feature vectors in an efficient way; (iii) publish-subscribe models are integrated both to spread data from sensors and orchestrate the nodes (communication and replication) for computing AR and (iv) machine learning algorithms are used to classify and recognize the activities. A successful case study of daily activities recognition developed in the Smart Lab of The University of Almería (UAL) is presented in this paper. Results present an encouraging performance in recognition of sequences of activities and show the need for distributed architectures to achieve real time recognition.

A New Architecture Based on IoT and Machine Learning Paradigms in Photovoltaic Systems to Nowcast Output Energy.

The classic models used to predict the behavior of photovoltaic systems, which are based on the physical process of the solar cell, are limited to defining the analytical equation to obtain its electrical parameter. In this paper, we evaluate several machine learning models to nowcast the behavior and energy production of a photovoltaic (PV) system in conjunction with ambient data provided by IoT environmental devices. We have evaluated the estimation of output power generation by human-crafted features with multiple temporal windows and deep learning approaches to obtain comparative results regarding the analytical models of PV systems in terms of error metrics and learning time. The ambient data and ground truth of energy production have been collected in a photovoltaic system with IoT capabilities developed within the Opera Digital Platform under the UniVer Project, which has been deployed for 20 years in the Campus of the University of Jaén (Spain). Machine learning models offer improved results compared with the state-of-the-art analytical model, with significant differences in learning time and performance. The use of multiple temporal windows is shown as a suitable tool for modeling temporal features to improve performance.

Fuzzy monitoring of in-bed postural changes for the prevention of pressure ulcers using inertial sensors attached to clothing.

Postural changes while maintaining a correct body position are the most efficient method of preventing pressure ulcers. However, executing a protocol of postural changes over a long period of time is an arduous task for caregivers. To address this problem, we propose a fuzzy monitoring system for postural changes which recognizes in-bed postures by means of micro inertial sensors attached to patients' clothes. First, we integrate a data-driven model to classify in-bed postures from the micro inertial sensors which are located in the socks and t-shirt of the patient. Second, a knowledge-based fuzzy model computes the priority of postural changes for body zones based on expert-defined protocols. Results show encouraging performance in the classification of in-bed postures and high adaptability of the knowledge-based fuzzy approach.

Insight into the potential application of polyphenol-rich dietary intervention in degenerative disease management.

In recent times, a great number of plants have been studied in order to identify new components with nutraceutical properties, among which are polyphenols. Dietary polyphenols represent a large group of bioactive molecules widely found in the food of plant origin and they have been found able to prevent the onset and progression of degenerative diseases, and to reduce and control their symptoms. These health protective effects have been mainly related to their antioxidant and anti-inflammatory properties. However, it must be considered that the application of isolated polyphenols as nutraceuticals is quite limited due to their poor systemic distribution and relative bioavailability. The present review highlights the potential effect of dietary intervention with polyphenol-rich food and plant extracts in patients with cancer, diabetes and neurodegenerative, autoimmune, cardiovascular and ophthalmic diseases, as well as the possible molecular mechanisms of action suggested in numerous studies with animal models.

Efficient Activity Recognition in Smart Homes Using Delayed Fuzzy Temporal Windows on Binary Sensors.

Human activity recognition has become an active research field over the past few years due to its wide application in various fields such as health-care, smart home monitoring, and surveillance. Existing approaches for activity recognition in smart homes have achieved promising results. Most of these approaches evaluate real-time recognition of activities using only sensor activations that precede the evaluation time (where the decision is made). However, in several critical situations, such as diagnosing people with dementia, "preceding sensor activations" are not always sufficient to accurately recognize the inhabitant's daily activities in each evaluated time. To improve performance, we propose a method that delays the recognition process in order to include some sensor activations that occur after the point in time where the decision needs to be made. For this, the proposed method uses multiple incremental fuzzy temporal windows to extract features from both preceding and some oncoming sensor activations. The proposed method is evaluated with two temporal deep learning models (convolutional neural network and long short-term memory), on a binary sensor dataset of real daily living activities. The experimental evaluation shows that the proposed method achieves significantly better results than the real-time approach, and that the representation with fuzzy temporal windows enhances performance within deep learning models.

Activity Recognition for IoT Devices Using Fuzzy Spatio-Temporal Features as Environmental Sensor Fusion.

The IoT describes a development field where new approaches and trends are in constant change. In this scenario, new devices and sensors are offering higher precision in everyday life in an increasingly less invasive way. In this work, we propose the use of spatial-temporal features by means of fuzzy logic as a general descriptor for heterogeneous sensors. This fuzzy sensor representation is highly efficient and enables devices with low computing power to develop learning and evaluation tasks in activity recognition using light and efficient classifiers. To show the methodology's potential in real applications, we deploy an intelligent environment where new UWB location devices, inertial objects, wearable devices, and binary sensors are connected with each other and describe daily human activities. We then apply the proposed fuzzy logic-based methodology to obtain spatial-temporal features to fuse the data from the heterogeneous sensor devices. A case study developed in the UJAmISmart Lab of the University of Jaen (Jaen, Spain) shows the encouraging performance of the methodology when recognizing the activity of an inhabitant using efficient classifiers.

Gold as a Possible Alternative to Platinum-Based Chemotherapy for Colon Cancer Treatment.

Due to the increasing incidence and high mortality associated with colorectal cancer (CRC), novel therapeutic strategies are urgently needed. Classic chemotherapy against CRC is based on oxaliplatin and other cisplatin analogues; however, platinum-based therapy lacks selectivity to cancer cells and leads to deleterious side effects. In addition, tumor resistance to oxaliplatin is related to chemotherapy failure. Gold(I) derivatives are a promising alternative to platinum complexes, since instead of interacting with DNA, they target proteins overexpressed on tumor cells, thus leading to less side effects than, but a comparable antitumor effect to, platinum derivatives. Moreover, given the huge potential of gold nanoparticles, the role of gold in CRC chemotherapy is not limited to gold(I) complexes. Gold nanoparticles have been found to be able to overcome multidrug resistance along with reduced side effects due to a more efficient uptake of classic drugs. Moreover, the use of gold nanoparticles has enhanced the effect of traditional therapies such as radiotherapy, photothermal therapy, or photodynamic therapy, and has displayed a potential role in diagnosis as a consequence of their optic properties. Herein, we have reviewed the most recent advances in the use of gold(I) derivatives and gold nanoparticles in CRC therapy.

Protein Hydrolysates from Fenugreek (Trigonella foenum graecum) as Nutraceutical Molecules in Colon Cancer Treatment.

The application of plant extracts for therapeutic purposes has been used in traditional medicine since the plants are a source of a great variety of chemical compounds that possess biological activity. Actually, the effect of these extracts on diseases such as cancer is being widely studied. Colorectal adenocarcinoma is one of the main causes of cancer related to death and the second most prevalent carcinoma in Western countries. The aim of this work is to study the possible effect of two fenugreek (Trigonella foenum graecum) protein hydrolysates on treatment and progression of colorectal cancer. Fenugreek proteins from seeds were hydrolysed by using two enzymes separately, which are named Purafect and Esperase, and were then tested on differentiated and undifferentiated human colonic adenocarcinoma Caco2/TC7 cells. Both hydrolysates did not affect the growth of differentiated cells, while they caused a decrease in undifferentiated cell proliferation by early apoptosis and cell cycle arrest in phase G1. This was triggered by a mitochondrial membrane permeabilization, cytochrome C release to cytoplasm, and caspase-3 activation. In addition, the hydrolysates of fenugreek proteins displayed antioxidant activity since they reduce the intracellular levels of ROS. These findings suggest that fenugreek protein hydrolysates could be used as nutraceutical molecules in colorectal cancer treatment.

Proteasome versus Thioredoxin Reductase Competition as Possible Biological Targets in Antitumor Mixed Thiolate-Dithiocarbamate Gold(III) Complexes.

New mixed gold(III) derivatives with dithiocarbamate and thiolate ligands have been synthesized and characterized. They display high anticancer activity against colon cancer cell lines without affecting to differentiated enterocytes, high stability in phosphate-buffered saline solution, and resistance to gold reduction in the presence of reducing agents in the majority of the derivatives. Some of them show interaction with thioredoxin reductase as derived from in vitro analysis and computational studies. However, a competition between this enzyme and proteasome is detected in cells, which is corroborated by the determination of proteasomal chymotrypsin-like activity inhibition. In addition, some of these dithiocarbamate gold(III) derivatives reduce cell viability and proliferation by intrinsic apoptotic pathway, with changes in mitochondrial membrane potential, cytochrome c release and caspase-3 activation. Consequently, our results show new complexes with proteasome as possible target in colorectal cancer.

Real-Time Monitoring in Home-Based Cardiac Rehabilitation Using Wrist-Worn Heart Rate Devices.

Cardiac rehabilitation is a key program which significantly reduces the mortality in at-risk patients with ischemic heart disease; however, there is a lack of accessibility to these programs in health centers. To resolve this issue, home-based programs for cardiac rehabilitation have arisen as a potential solution. In this work, we present an approach based on a new generation of wrist-worn devices which have improved the quality of heart rate sensors and applications. Real-time monitoring of rehabilitation sessions based on high-quality clinical guidelines is embedded in a wearable application. For this, a fuzzy temporal linguistic approach models the clinical protocol. An evaluation based on cases is developed by a cardiac rehabilitation team.

Alkynyl gold(I) complex triggers necroptosis via ROS generation in colorectal carcinoma cells.

Given the rise of apoptosis-resistant tumors, there exist a growing interest in developing new drugs capable of inducing different types of cell death to reduce colorectal cancer-related death rates. As apoptosis and necroptosis do not share cellular machinery, necroptosis induction may have a great therapeutic potential on those apoptosis-resistant cancers, despite the inflammatory effects associated with it. We have synthesized an alkynyl gold(I) complex [Au(CC-2-NC5H4)(PTA)] whose anticancer effect was tested on the colorectal adenocarcinoma Caco-2 cell line. With regard to its mechanism of action, this gold complex enters the mitochondria and disrupts its normal function, leading to an increase in ROS production, which triggers necroptosis. Necroptosis induction has been found dependent of TNF-α (Tumor necrosisfactor α) and TNFR1(Tumor necrosisfactor receptor 1) binding, RIP1(Receptor-Interacting Protein 1) activation and NF-κB (Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells) signaling. Moreover, the antitumor potential of [Au(CC-2-NC5H4)(PTA)] has also been confirmed on the 3D cancer model spheroid. Overall, the obtained data show firstly that gold complexes might have the ability of inducing necroptosis, and secondarily that our compound [Au(CC-2-NC5H4)(PTA)] is an interesting alternative to current chemotherapy drugs in cases of apoptosis resistance.