Natural Products for the Prevention and Treatment of Oral Mucositis—A Review

Cancer, a major world public health problem, is associated with chemotherapy treatments whose administration leads to secondary concerns, such as oral mucositis (OM). The OM disorder is characterized by the presence of ulcers in the oral mucosa that cause pain, bleeding, and difficulty in ingesting fluids and solids, or speaking. Bioactive compounds from natural sources have arisen as an effective approach for OM. This review aims to summarize the new potential application of different natural products in the prevention and treatment of OM in comparison to conventional ones, also providing a deep insight into the most recent clinical studies. Natural products, such as Aloe vera, Glycyrrhiza glabra, Camellia sinensis, Calendula officinalis, or honeybee crops, constitute examples of sources of bioactive compounds with pharmacological interest due to their well-reported activities (e.g., antimicrobial, antiviral, anti-inflammatory, analgesic, or wound healing). These activities are associated with the bioactive compounds present in their matrix (such as flavonoids), which are associated with in vivo biological activities and minimal or absent toxicity. Finally, encapsulation has arisen as a future opportunity to preserve the chemical stability and the drug bioa vailability of bioactive compounds and, most importantly, to improve the buccal retention period and the therapeutic effects.     

Evaluation of wastewater toxicity: comparative study between Microtox and activated sludge oxygen uptake inhibition

Microtox is a frequent toxicity tool for the screening of wastewaters discharged into wastewater treatment plants. There is currently an increasing controversy between this test and others using activated sludge. A Microtox and electrolytic respirometry comparative study for toxicity determination has been performed. Seven organic and five inorganic toxic compounds have been assessed for comparing both methods. Microtox proved to have a higher sensitivity to toxicants but was less representative of effects on activated sludge compared to respirometry. For instance, assays accomplished with LAS, a biodegradable reference surfactant, showed a toxic effect by Microtox but good biodegradability and no toxicity in respirometry. This could be explained by the different nature of the biological material used, as Microtox utilises the seawater Vibrio fischeri, whereas respirometry uses the bacterial consortium in activated sludge. For the evaluation of the potential toxicity of a compound on a WWTP, the preferred biological material be used should be activated sludge itself. Results obtained with any other biological material would be just an approach to reality.     

Dual-stage sugar substitution in strawberries with a Stevia-based sweetener

The present study introduces and analyzes a new process denominated dual-stage sugar substitution (D3S). This process aims to induce sugar substitution in strawberries. In a first stage, high-calorie sugars (sucrose, fructose and glucose) are partially removed from the fruit samples and in a second stage, low-calorie sugar (stevioside and rebaudioside) is incorporated to the fruit to maintain its sweetness. The process was evaluated by studying the use of ultrasound application in one or both stages of the D3S process. Best performance of the process was obtained by subjecting the fruit samples to ultrasound in the sugar removal stage followed by immersion of the samples in Stevia-based solution without application of ultrasound in the sweetener incorporation stage. These operating conditions result in the highest sugar removal during the first stage, highest water loss during the process and highest sweetener incorporation during the second stage of the D3S process.Industrial relevanceThe work described in this research is relevant to the production of dried fruits. A process to produce low-calorie dried fruit is presented. The process removes high-calorie sugars from the fruit and replaces it with a natural low-calorie sugar restoring the sweetness of the fruit.     

Microbial and sensory changes during refrigerated storage of desalted cod (Gadus morhua) preserved by combined methods

Water blanching and the use of additives (potassium sorbate and citric acid) combined with different types of packaging (air, vacuum "VP" and modified atmosphere packaging "MAP": 60% CO(2), 30% N(2) and 10% O(2)), were studied as new methods of preservation of chilled desalted cod. Microbial counts and total volatile basic nitrogen (TVB-N) analyses were carried out during a period of 42 days on all samples stored at 4 degrees C. No Aeromonas or sulphite-reducing Clostridium were isolated from any of the analysed samples. The lowest microbial counts of mesophilic, psychrotrophic, Pseudomonas, moulds and yeasts, were found in samples with additives in all kinds of packaging. These samples in VP or MAP maintained an excellent microbial quality throughout the 42 days of storage, with mesophilic and psychrotrophic counts always below 4 log CFU/g. Counts of the four microorganisms above-mentioned in blanched samples packaged with air, exceeded 5 log CFU/g on days 21-28, so it became necessary to use VP or MAP to maintain these microorganisms at an acceptable level for the entire storage period. TVB-N contents were low in samples with additives, regardless of the kind of packaging, as well as in blanched samples packaged in VP and MAP, never reaching 25 mg/100 g. Since there were no significant differences either in microbial growth or in TVB-N between samples in VP and MAP, a sensory analysis was performed only in desalted cod submitted to the two treatments (blanching and additives) combined with VP, both in raw and cooked samples. The results of this analysis showed that the addition of potassium sorbate and citric acid did not alter the typical organoleptic features of desalted cod. The sensory characteristics of both blanched samples and those with additives in VP showed no change during the period of the study.     

Synthesis of Four Steroidal Carbamates with Antitumor Activity against Mouse Colon Carcinoma CT26WT Cells: In Vitro and In Silico Evidence

Colorectal cancer (CRC) is one of the most lethal cancers worldwide. If detected on time, surgery can expand life expectations of patients up to five more years. However, if metastasis has grown deliberately, the use of chemotherapy can play a crucial role in CRC control. Moreover, the lack of selectivity of current anticancer drugs, plus mutations that occur in cancerous cells, demands the development of new chemotherapeutic agents. Several steroids have shown their potentiality as anticancer agents, while some other compounds, such as Taxol and its derivatives bearing a carbamate functionality, have reached the market. In this article, the synthesis, characterization, and antiproliferative activity of four steroidal carbamates on mouse colon carcinoma CT26WT cells are described. Carbamate synthesis occurred via direct reaction between diosgenin, its B-ring modified derivative, and testosterone with phenyl isocyanate under a Brønsted acid catalysis. All obtained compounds were characterized by ¹H and ¹³C Nuclear Magnetic Resonance (NMR), High Resolution Mass Spectroscopy (HRMS); their melting points are also reported. Results obtained from antiproliferative activity assays indicated that carbamates compounds have inhibitory effects on the growth of this colon cancer cell line. A molecular docking study carried out on Human Prostaglandin E Receptor (EP4) showed a high affinity between carbamates and protein, thus providing a valuable theoretical explanation of the in vitro results.     

Using UML Profiles for Documenting Web-Based Application Frameworks

The Web now offers an exceptional infrastructure for the development of distributed collaborative services and applications. However, most of the existing applications only make use of the Web access and visualization facilities, without exploiting its distributed-processing potential capabilities. Web technologies are currently more focused on the provision of semantics to data and the design of dynamic Web pages, while paying little attention to the distributed architecture of the applications – that should go beyond client-server architectures. Application frameworks are one of the key technologies that may provide the mechanisms required for the design and development of reusable and scalable systems in these environments. However, the way to document such frameworks so they can be effectively tailored and reused still remains unresolved. In this paper we propose the use of UML profiles for documenting Web-based application frameworks, as a standard means for expressing their semantics. UML profiles allow all stakeholders of a system to share a common graphical notation and vocabulary, and permit more precise specifications and better documentation on how to use and customize applications. As an example, we build a UML profile for MultiTEL, a framework particularly well suited for the development of Internet-based multimedia and collaborative systems, and show how systems designers can use it to derive and document their applications.     

GABAergic Regulation of Astroglial Gliotransmission through Cx43 Hemichannels

Gamma-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain. It is produced by interneurons and recycled by astrocytes. In neurons, GABA activates the influx of Cl^- via the GABA_A receptor or efflux or K⁺ via the GABA_B receptor, inducing hyperpolarization and synaptic inhibition. In astrocytes, the activation of both GABA_A and GABA_B receptors induces an increase in intracellular Ca²⁺ and the release of glutamate and ATP. Connexin 43 (Cx43) hemichannels are among the main Ca²⁺-dependent cellular mechanisms for the astroglial release of glutamate and ATP. However, no study has evaluated the effect of GABA on astroglial Cx43 hemichannel activity and Cx43 hemichannel-mediated gliotransmission. Here we assessed the effects of GABA on Cx43 hemichannel activity in DI NCT1 rat astrocytes and hippocampal brain slices. We found that GABA induces a Ca²⁺-dependent increase in Cx43 hemichannel activity in astrocytes mediated by the GABA_A receptor, as it was blunted by the GABA_A receptor antagonist bicuculline but unaffected by GABA_B receptor antagonist {"type":"entrez-protein","attrs":{"text":"CGP55845","term_id":"875097176","term_text":"CGP55845"}}CGP55845. Moreover, GABA induced the Cx43 hemichannel-dependent release of glutamate and ATP, which was also prevented by bicuculline, but unaffected by CGP. Gliotransmission in response to GABA was also unaffected by pannexin 1 channel blockade. These results are discussed in terms of the possible role of astroglial Cx43 hemichannel-mediated glutamate and ATP release in regulating the excitatory/inhibitory balance in the brain and their possible contribution to psychiatric disorders.     

仿生土木工程研究进展与展望

随着城镇化水平不断提升,中国每年新增建筑面积约20亿m²,大规模基础设施建设对土木工程理论和技术创新的要求越来越高。学者们通过研究自然界的增强增韧、水下黏合、钻孔掘进和轻质高强等现象发现,生物体具有独特的外部形态和组织结构,通过模仿生物体的外部形态、结构特征或运动机理可为土木工程技术创新和可持续发展提供新思路、新原理和新理论。从仿生材料、仿生结构和仿生机械与构筑物3个方面阐述仿生学在土木工程中的应用,列举典型的应用案例,并对仿生土木工程进行总结和展望,为未来的研究提供基础材料。作为新兴的研究方向,仿生土木工程基础理论尚不完善,仿生土木工程涉及生物、材料、结构等多学科的交叉,需要开展不同领域间的协同合作研究。     

A technical characterization of APTs by leveraging public resources

Advanced persistent threats (APTs) have rocketed over the last years. Unfortunately, their technical characterization is incomplete—it is still unclear if they are advanced usages of regular malware or a different form of malware. This is key to develop an effective cyberdefense. To address this issue, in this paper we analyze the techniques and tactics at stake for both regular and APT-linked malware. To enable reproducibility, our approach leverages only publicly available datasets and analysis tools. Our study involves 11,651 regular malware and 4686 APT-linked ones. Results show that both sets are not only statistically different, but can be automatically classified with F1 > 0.8 in most cases. Indeed, 8 tactics reach F1 > 0.9. Beyond the differences in techniques and tactics, our analysis shows thats actors behind APTs exhibit higher technical competence than those from non-APT malwares.

     

Vitis vinifera L. Bioactive Components Modulate Adipose Tissue Metabolic Markers of Healthy Rats in a Photoperiod-Dependent Manner

Scope

The beneficial health effects of (poly)phenol-rich foods such as red grapes mainly depend on both the type and concentration of (poly)phenols. Since fruit (poly)phenol content is influenced by growing conditions, the study examines the seasonal effects of red grapes (Vitis vinifera L.), grown under various cultivation conditions, on metabolic markers of adipose tissue in healthy rats.

Methods and results

For this purpose, Fischer 344 rats are exposed into three different light-dark cycles and daily supplemented with 100 mg kg⁻¹ of either conventionally or organically grown red grapes for 10 weeks (n = 6). Seasonal consumption of organic grapes (OGs), which are richer in anthocyanins, increases energy expenditure (EE) of animals exposed to long photoperiod and enhances uncoupling protein 1 (UCP1) protein expression in brown adipose tissue of animals under standard photoperiod. Additionally, red grape consumption affects the gene expression profile of white adipose tissue (WAT), upregulating browning markers of subcutaneous WAT in 12 h light (L12) and 18 h light (L18) photoperiods, and downregulating adipogenic and lipolytic markers of visceral WAT in 6 h light (L6) and L12 photoperiods.

Conclusions

These results clearly show that bioactive compounds of grapes can modulate the metabolic markers of white and brown adipose tissues in a photoperiod and depot-dependent manner, partly affecting EE when consumed out of season.