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Extraordinary progress has been made over the past decade in the chemical synthesis of many stilbene oligomers (>2) as well as in biotechnological methods for the production of these compounds.

Brain cancer is an aggressive type of cancer with poor prognosis. While the immune system protects against cancer in the early stages, the tumor exploits the healing arm of inflammatory reactions to accelerate its growth and spread. Various immune cells penetrate the developing tumor region, establishing a pro-inflammatory tumor milieu. Additionally, tumor cells may release chemokines and cytokines to attract immune cells and promote cancer growth. Inflammation and its associated mechanisms in the progression of cancer have been extensively studied in the majority of solid tumors, especially brain tumors. However, treatment of the malignant brain cancer is hindered by several obstacles, such as the blood-brain barrier, transportation inside the brain interstitium, inflammatory mediators that promote tumor growth and invasiveness, complications in administering therapies to tumor cells specifically, the highly invasive nature of gliomas, and the resistance to drugs. To resolve these obstacles, nanomedicine could be a potential strategy that has facilitated advancements in diagnosing and treating brain cancer. Due to the numerous benefits provided by their small size and other features, nanoparticles have been a prominent focus of research in the drug-delivery field. The purpose of this article is to discuss the role of inflammatory mediators and signaling pathways in brain cancer as well as the recent advances in understanding the nano-carrier approaches for enhancing drug delivery to the brain in the treatment of brain cancer.

The existing pandemic viral infection caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) leads to coronavirus disease 2019 (Covid-19). SARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as an entry-point into affected cells and down-regulation of ACE2 by this virus triggers the release of pro-inflammatory cytokines and up-regulation of angiotensin II. These changes may lead to hypercytokinemia and the development of cytokine storm with the development of acute lung injury and acute respiratory distress syndrome. Different repurposed had been in use in the management of Covid-19, one of these agents is pentoxifylline (PTX) which has anti-inflammatory and antioxidant properties. Therefore, the objective of the present mini-review is to highlight the potential role of PTX in Covid-19 regarding its anti-inflammatory and antioxidant effects. PTX is a non-selective phosphodiesterase inhibitor that increases intracellular cyclic adenosine monophosphate which stimulates protein kinase A and inhibits leukotriene and tumor necrosis factor. PTX has antiviral, anti-inflammatory and immunomodulatory effects, thus it may attenuate SARS-CoV-2-induced hyperinflammation and related complications. As well, PTX can reduce hyper-viscosity and coagulopathy in Covid-19 through increasing red blood cell deformability and inhibition of platelet aggregations. In conclusion, PTX is a non-selective phosphodiesterase drug, that has anti-inflammatory and antioxidant effects thereby can reduce SARS-CoV-2 infection-hyperinflammation and oxidative stress. Besides, PTX improves red blood cells (RBCs) deformability and reduces blood viscosity so can mitigate Covid-19-induced hyper-viscosity and RBCs hyper-aggregation which is linked with the development of coagulopathy. Taken together, PTX seems to be an effective agent against Covid-19 severity.

During the last decades, many numerical models have been developed to explore the conditions for seismic and aseismic slip. Those models explore the behavior of frictional faults, embedded in either elastic or inelastic mediums, and submitted to a far field loading (seismic cycle models), or initial stresses (single dynamic rupture models). Those initial conditions impact both fault and off-fault dynamics. Because of the sparsity of direct measurements of fault stresses, modelers have to make assumptions about the initial conditions. To these days, Anderson theory is the only framework that can be used to link fault generation and reactivation to the three-dimensional stress field. In this study, we focus on the initial stresses in 2D plane strain models developed to compute off-fault deformation. It has been demonstrated that initial conditions, in particular the angle between fault and the greatest compressive stress, is of crucial importance for the localization and intensity of off-fault inelastic deformation. However, because those models are performed on a 2D plane, the importance of the out-of-plane stress have never been investigated. We show that it can lead to set up a stress field that is not in agreement with Anderson theory (i.e., modelling a strike-slip fault in a three-dimensional stress field appropriate for reverse faulting). We investigate the influence of initial stresses by comparing equivalent models with “correct” and “incorrect” initial stress fields, keeping constant rupture-related parameters (stress drop, seismic ratio), angle between fault and greatest principal stress, and depth. We first use purely elastic models to study the influence of initial stresses on the assessment of two plastic criteria (Drucker-Prager and Coulomb stress change). We show that setting up the incorrect initial stress field can lead to underestimating the different yield criteria. The error is of the order of magnitude of the dynamic stress drop. Moreover, setting up the incorrect pre-stresses leads to errors in the estimation of potential off-fault failure modes. Then, we explore the influence of pre-stresses conditions on off-fault inelastic deformation. Using two different modelling strategies (a plastic deformation model and a micromechanics model computing dynamic damage), we show that setting up the incorrect stress field can lead to underestimate the size of the damage zone by a factor of 3 to 6 for the studied cases. Moreover, because of the interactions between fault slip and off-fault deformation, we show that initial stress field influences the rupture propagation. Setting up the correct stress field can significantly slow the rupture, because of the more important quantity of damage induced.

The JUpiter ICy moons Explorer (JUICE) mission is the first large-class (L1) mission of ESA Cosmic Vision. JUICE will be launched in April 2023 with an arrival at Jupiter in 2031 and at least four years making detailed observations of Jupiter’s magnetosphere and of three of its largest moons (Ganymede, Callisto and Europa). The Radio and Plasma Wave Investigation (RPWI) consortium will carry the most advanced set of electric and magnetic fields sensors ever flown in Jupiter’s magnetosphere, which will allow to characterize the radio emission and plasma wave environment of Jupiter and its icy moons. Here we present the scientific objectives and the technical features of the Search Coil Magnetometer (SCM) of RPWI. SCM will provide for the first time three-dimensional measurements of magnetic field fluctuations in the frequency range 0.1 Hz – 20 kHz within Jupiter’s magnetosphere. High sensitivity (~10 fT / √Hz at 1 kHz) will be assured by combining an optimized (20 cm long) magnetic transducer with a low-noise (4 nV / √Hz) ASIC pre-amplifier. Perturbations by the spacecraft are strongly reduced by accommodating SCM at about 10 m away from the spacecraft on the JUICE magnetometer boom. The combination of high sensitivity and high cleanliness of SCM measurements will allow unpreceded studies of electromagnetic fluctuations down to plasma kinetic scales, in particular in key regions such as the magnetopause, the auroral region and the magnetotail current sheet of Ganymede’s own magnetosphere which JUICE will orbit for many months. This will lead to important advances in understanding how fundamental plasma processes such as magnetic reconnection, turbulence and particle energization occur in Jupiter’s plasma environment.

Faults are complex systems embedded in an evolving medium fractured by seismic ruptures. This off-fault damage zone is shown to be thermo-hydro-mechano-chemically coupled to the main fault plane by a growing number of studies. Yet, off-fault medium is still, for the most part modelled as a purely elastic -- hence passive -- medium. Using a micromechanical model we investigate the depth variation of dynamically triggered off-fault damage and its counter-impact on earthquake slip dynamics. We show that if the damage zone becomes narrower with depth, it is also denser and thus, unlike what is commonly believed, remains an energy sink even at depth. The results are in agreement with the complementary model by Okubo et al., 2019. In contrast to study cited above, our model accounts for the dynamics changes of elastic moduli related to crack growth. This lead to the dynamic creation of low-velocity zone that can trapped seismic waves and further impact the earthquake dynamics, even at greater depth. We therefore claim that the intertwined dynamics between the main fault plane and its surrounding medium must be including along the all seismogenic.

Background Following the SARS-CoV-2 Omicron variant spread, the use of unsupervised antigenic rapid diagnostic tests (self-tests) increased. Aim This study aimed to measure self-test uptake and factors associated with self-testing. Methods In this cross-sectional study from 20 January to 2 May 2022, the case series from a case–control study on factors associated with SARS-CoV-2 infection were used to analyse self-testing habits in France. A multivariable quasi-Poisson regression was used to explore the variables associated with self-testing among symptomatic cases who were not contacts of another infected individual. The control series from the same study was used as a proxy for the self-test background rate in the non-infected population of France. Results During the study period, 179,165 cases who tested positive through supervised tests were recruited. Of these, 64.7% had performed a self-test in the 3 days preceding this supervised test, of which 79,038 (68.2%) were positive. The most frequently reported reason for self-testing was the presence of symptoms (64.6%). Among symptomatic cases who were not aware of being contacts of another case, self-testing was positively associated with being female, higher education, household size, being a teacher and negatively associated with older age, not French by birth, healthcare-related work and immunosuppression. Among the control series, 12% self-tested during the 8 days preceding questionnaire filling, with temporal heterogeneity. Conclusion The analysis showed high self-test uptake in France with some inequalities which must be addressed through education and facilitated access (cost and availability) for making it a more efficient epidemic control tool.

The human oral cavity is comprised of dynamic and polynomial microbes which uniquely reside in the microenvironments of oral cavities. The cumulative functions of the symbiotic microbial communities maintain normal homeostasis; however, a shifted microbiota yields a dysbiosis state, which produces local and systemic diseases including dental caries, periodontitis, cancer, obesity and diabetes. Recent research reports claim that an association occurs between oral dysbiosis and the progression of different types of cancers including oral, gastric and pancreatic ones. Different mechanisms are proposed for the development of cancer, such as induction of inflammatory reactions, production of carcinogenic materials and alteration of the immune system. Medications are available to treat these associated diseases; however, the current strategies may further worsen the disease by unwanted side effects. Natural-derived polyphenol molecules significantly inhibit a wide range of systemic diseases with fewer side effects. In this review, we have displayed the functions of the oral microbes and we have extended the report regarding the role of polyphenols in oral microbiota to maintain healthy conditions and prevention of diseases with emphasis on the treatment of oral microbiota-associated cancer.

Dipeptidyl peptidase-4 (DPP-IV) inhibitors are known as safe and well-tolerated antidiabetic medicine. Therefore, the aim of the present work was to synthesize some carbohydrazide derivatives (1a–5d) as DPP-IV inhibitors. In addition, this work involves simulations using molecular docking, ADMET analysis, and Lipinski and Veber’s guidelines. Wet-lab synthesis was used to make derivatives that met all requirements, and then FTIR, NMR, and mass spectrometry were used to confirm the structures and perform biological assays. In this context, in vitro enzymatic and in vivo antidiabetic activity evaluations were carried out. None of the molecules had broken the majority of the drug-likeness rules. Furthermore, these molecules were put through additional screening using molecular docking. In molecular docking experiments (PDB ID: 2P8S), many molecules displayed more potent interactions than native ligands, exhibiting more hydrogen bonds, especially those with chloro- or fluoro substitutions. Our findings indicated that compounds 5b and 4c have IC50 values of 28.13 and 34.94 µM, respectively, under in vitro enzymatic assays. On the 21st day of administration to animals, compound 5b exhibited a significant reduction in serum blood glucose level (157.33 ± 5.75 mg/dL) compared with the diabetic control (Sitagliptin), which showed 280.00 ± 13.29 mg/dL. The antihyperglycemic activity showed that the synthesized compounds have good hypoglycemic potential in fasting blood glucose in the type 2 diabetes animal model (T2DM). Taken all together, our findings indicate that the synthesized compounds exhibit excellent hypoglycemic potential and could be used as leads in developing novel antidiabetic agents.

Plants offer an ecosystem for microorganisms from diverse phylogenetic domains and phyla as well as viruses and viroids [...]

Polydatin or 3-O-β-d-resveratrol-glucopyranoside (PD), a stilbenoid component of Polygonum cuspicadum (Polygonaceae), has a variety of biological roles. In traditional Chinese medicine, P. cuspicadum extracts are used for the treatment of infections, inflammation, and cardiovascular disorders. Polydatin possesses a broad range of biological activities including antioxidant, anti-inflammatory, anticancer, and hepatoprotective, neuroprotective, and immunostimulatory effects. Currently, a major proportion of the population is victimized with cervical lung cancer, ovarian cancer and breast cancer. PD has been recognized as a potent anticancer agent. PD could effectively inhibit the migration and proliferation of ovarian cancer cells, as well as the expression of the PI3K protein. The malignancy of lung cancer cells was reduced after PD treatments via targeting caspase 3, arresting cancer cells at the S phase and inhibiting NLRP3 inflammasome by downregulation of the NF-κB pathway. This ceases cell cycle, inhibits VEGF, and counteracts ROS in breast cancer. It also prevents cervical cancer by regulating epithelial-to-mesenchymal transition (EMT), apoptosis, and the C-Myc gene. The objective of this review is thus to unveil the polydatin anticancer potential for the treatment of various tumors, as well as to examine the mechanisms of action of this compound.

Prostate cancer (PCa) is the leading cause of cancer death in men, and its treatment is commonly associated with severe adverse effects. Thus, new treatment modalities are required. In this context, natural compounds have been widely explored for their anti-PCa properties. Aquatic organisms contain numerous potential medications. Anticancer peptides are less toxic to normal cells and provide an efficacious treatment approach via multiple mechanisms, including altered cell viability, apoptosis, cell migration/invasion, suppression of angiogenesis and microtubule balance disturbances. This review sheds light on marine peptides as efficacious and safe therapeutic agents for PCa.

Editorial on the Research Topic: Opportunities and Challenges for Drug Discovery from Natural Products in the Pharmacotherapy of Neurological Disorders

This review provides an overview on the role of camalexin in plant immunity taking into account various plant-pathogen and beneficial microbe interactions, regulation mechanisms and the contribution in basal and induced plant resistance. In a hostile environment, plants evolve complex and sophisticated defense mechanisms to counteract invading pathogens and herbivores. Several lines of evidence support the assumption that secondary metabolites like phytoalexins which are synthesized de novo, play an important role in plant defenses and contribute to pathogens' resistance in a wide variety of plant species. Phytoalexins are synthesized and accumulated in plants upon pathogen challenge, root colonization by beneficial microbes, following treatment with chemical elicitors or in response to abiotic stresses. Their protective properties against pathogens have been reported in various plant species as well as their contribution to human health. Phytoalexins are synthesized through activation of particular sets of genes encoding specific pathways. Camalexin (3'-thiazol-2'-yl-indole) is the primary phytoalexin produced by Arabidopsis thaliana after microbial infection or abiotic elicitation and an iconic representative of the indole phytoalexin family. The synthesis of camalexin is an integral part of cruciferous plant defense mechanisms. Although the pathway leading to camalexin has been largely elucidated, the regulatory networks that control the induction of its biosynthetic steps by pathogens with different lifestyles or by beneficial microbes remain mostly unknown. This review thus presents current knowledge regarding camalexin biosynthesis induction during plant-pathogen and beneficial microbe interactions as well as in response to microbial compounds and provides an overview on its regulation and interplay with signaling pathways. The contribution of camalexin to basal and induced plant resistance and its detoxification by some pathogens to overcome host resistance are also discussed.

Due to their role as energy and carbon sources and their regulatory functions, sugars influence all phases of the plant life cycle, interact with other signaling molecules, including phytohormones, and control plant growth and development [...]

Magnetic field draping occurs when the magnetic field lines frozen in a plasma flow wrap around a body or plasma environment. The draping of the interplanetary magnetic field (IMF) around the Earth's magnetosphere has been confirmed in the early days of space exploration. However, its global and three-dimensional structure is known from modeling only, mostly numerical. Here, this structure in the dayside of the Earth's magnetosheath is determined as a function of the upstream IMF orientation purely from in-situ spacecraft observations. We show the draping structure can be organized in three distinct regimes depending on how radial the upstream IMF is. Quantitative analysis demonstrates how the draping pattern results from the frozen-in condition with the magnetosheath flow, deflected around the magnetopause.

Publisher Copyright: © 2023 by the authors. A new generation of clay-based nano pigments has been introduced, providing the advantage of both inorganic pigments and organic dyes. These nano pigments have been synthesized through a stepwise procedure where, initially, an organic dye is adsorbed onto the surface of the adsorbent, and then dye adsorbed adsorbent is used as pigment for further applications. The objective of the current paper was to examine the interaction of non-biodegradable toxic dyes, Crystal Violet (CV) and Indigo Carmine (IC), with clay minerals (montmorillonite (Mt), vermiculite (Vt), and clay bentonite (Bent)) and their organically modified forms (OMt, OBent, and OVt) and to develop a novel methodology for the synthesis of the value-added products and clay-based nano pigments without creating second generation waste materials. In our observation, the uptake of CV was more intense onto pristine Mt, Bent, and Vt, and the uptake of IC was more onto OMt, OBent, and OVt. CV was found to be in the interlayer region of Mt and Bent, as supported by XRD data. Zeta potential values confirmed the presence of CV on their surface. In contrast, in the case of Vt and organically modified forms, the dye was found on the surface, confirmed by XRD and zeta potential values. In the case of indigo carmine, the dye was found only on the surface of pristine Mt, Bent, Vt, and organo Mt, Bent, Vt. During the interaction of CV and IC with clay and organoclays, intense violet and blue-colored solid residues were obtained (also known as clay-based nano pigments). The nano pigments were used as colorants in a poly (methyl-methacrylate) (PMMA) polymer matrix to form transparent polymer films.

Neuroblastoma is the most prevalent extracranial solid tumor in pediatric patients, originating from sympathetic nervous system cells. Metastasis can be observed in approximately 70% of individuals after diagnosis, and the prognosis is poor. The current care methods used, which include surgical removal as well as radio and chemotherapy, are largely unsuccessful, with high mortality and relapse rates. Therefore, attempts have been made to incorporate natural compounds as new alternative treatments. Marine cyanobacteria are a key source of physiologically active metabolites, which have recently received attention owing to their anticancer potential. This review addresses cyanobacterial peptides’ anticancer efficacy against neuroblastoma. Numerous prospective studies have been carried out with marine peptides for pharmaceutical development including in research for anticancer potential. Marine peptides possess several advantages over proteins or antibodies, including small size, simple manufacturing, cell membrane crossing capabilities, minimal drug–drug interactions, minimal changes in blood–brain barrier (BBB) integrity, selective targeting, chemical and biological diversities, and effects on liver and kidney functions. We discussed the significance of cyanobacterial peptides in generating cytotoxic effects and their potential to prevent cancer cell proliferation via apoptosis, the activation of caspases, cell cycle arrest, sodium channel blocking, autophagy, and anti-metastasis behavior.

Understanding the mechanical properties of the off-fault medium and its interactions with earthquake rupture is essential for a better understanding of the behavior of fault zones. In this framework, two-dimensional, plane strain models are often used to investigate the interplay between seismic rupture propagation and inelastic deformation in the damage zone. The role of pre-stress conditions for faulting and damage has been studied, in particular the influence of Y, the angle between the largest principal stress and the fault strike. However, in plane strain conditions, the out-of-plane stress is often ignored when setting up the initial stress field, and its influence on dynamic rupture and stress evolution has not been inferred. In this study, we explore the role of the out-of-plane pre-stress for a 2D in-plane model in plane strain conditions. We model a 1D right-lateral, strike-slip vertical fault featuring slip-weakening friction law. We first demonstrate theoretically that if the out- of-plane stress is not considered properly in the initial stress field, pre-stress conditions may not correspond to actual strike-slip faulting. We then investigate how changing the initial stress field can influence the rupture and the stress evolution in the off-fault medium. Our results show that if it does not influence significantly the rupture dynamics, the out-of-plane stress is essential in controlling the evolution of the off-fault medium, especially the localization and extend of areas affected by plastic yielding. Therefore, our results demonstrate the importance of considering properly the initial out-of-plane stress to infer the extend, magnitude and distribution of damage in 2D plane strain simulations with off fault plastic deformation.

Understanding where the magnetic reconnection occurs at the Earth’s magnetopause is one of the important remaining questions about this phenomena. Since the last decades various models predicting the position of the X-line have been made. These models largely depend on the orientation of the magnetic field in the magnetosheath close to the magnetopause, such as the Maximum Magnetic Shear model (Trattner et al 2007). Therefore understanding how it is structured as a function of the solar wind and interplanetary magnetic field is of pivotal importance. Machine learning was used to collect around 45 million measurements in the magnetosheath at 5s resolution in all available Cluster, MMS, Double Star, THEMIS dataset, and to build detailed maps of the field structure in that region as a function of the IMF orientation. It allowed us to reconstruct for the first time the three dimensional magnetic field draping in the dayside magnetosheath from in-situ data only. Our results reveal how the frozen-in condition constrains the draping around the magnetopause. A comparison of the draping obtained with in-situ data with the one from a widely used magnetostatic model (Kobel et al 1994) was made. Differences of up to 180° were found for cone angle between 12.5° and 45°, for which the consequences regarding the position of the X-line will be discussed.

The SCIentific Qt application for Learning from Observations of Plasmas (SciQLop) project allows to easily discover, retrieve, plot and label in situ space physic measurements from remote servers such as Coordinated Data Analysis Web (CDAWeb) or Automated Multi-Dataset Analysis (AMDA). Analyzing data from a single instrument on a given mission can rise some technical difficulties such as finding where to get them, how to get them and sometimes how to read them. Thus building for example a machine-learning pipeline involving multiple instruments and even multiple spacecraft missions can be very challenging. Our goal here is to remove all these technical difficulties without sacrificing performances to allow scientist to focus on data analysis.SciQLop development has started in 2015 as a C++ graphical application funded by the Paris-Saclay Center for Data Science (CDS) then by Paris-Saclay SPACEOBS and finally it joined the Plasma Physics Data Center (CDPP) in 2019. It has evolved from a monolithic C++ graphical application to a collection of simple and reusable Python or C++ packages solving one problem at a time, increasing our chances to reach users and contributors.The SciQLop project is composed of the following tools:Speasy: An easy to use Python package to retrieve data from remote servers with multi-layer cache support. Speasy_proxy: A self-hostable, chainable remote cache for Speasy written as a simple Python package. Broni: A Python package which finds intersections between spacecraft trajectories and simple shapes or physical models such as magnetosheath. Orbit-viewer: A Python graphical user interface (GUI) for Broni. TSCat: A Python package used as backend for catalogs of events storage. TSCat-GUI: A Python graphical user interface (GUI). SciQLop-GUI: An extensible and efficient user interface to visualize and label time-series with an embedded IPYthon terminal. While some components are production ready and already used for science, SciQLop is still in development and the landscape is moving quite fast.In this presentation we will give an overview of SciQLop, demonstrate its benefits using some specific cases studies and finally discuss the planned features development.

It has been consistently demonstrated that physical exercise is a cost-effective way to promote emotional well-being. However, the environment in which it takes place might amplify or mitigate this beneficial effect. The present study aimed at comparing the effects of walking in a natural or urban field setting on positive and negative affect. For this purpose, 150 students (46 female, 104 male; mean age: 20.2 years) were randomized into one of three groups: Green Walking (GW

International audience; In a companion statistical study, we showed that the expression of the magnetopause surface as a power law of an elliptic function of the zenith angle θ holds at lunar distances, that the flaring of the magnetopause surface is influenced by the Interplanetary Magnetic Field (IMF) By component and that the IMF Bx component had no influence on the stand-off distance. As a follow-up to these statistical results, this paper presents a new empirical analytical asymmetric and non-indented model of the magnetopause location and shape. This model is obtained from fitting of 15,349 magnetopause crossings using 17 different spacecraft and is parametrized by the upstream solar wind dynamic and magnetic pressures, the IMF clock angle and the Earth dipole tilt angle. The constructed model provides a more accurate prediction of the magnetopause surface location than current Magnetopause surface models, especially on the night side of the magnetosphere.

Modern laser plasma accelerators require combination of high peak power and high average power from the laser. Ti:Sa CPA remaining the best technology for such purpose a high average power Ti:Sa amplifier has been developed

We report the demonstration of 100Hz, 300mJ TiSa amplifier. The amplifier is based on active-mirror concept, with efficient cooling capacity, and pumped by frequency-doubled Nd:YAG laser emitting 700mJ at 532nm.

International audience; The shape and location of the magnetopause current sheet in the near-cusp region is still a debated question. Over time, several observations led to contradictory conclusions regarding the presence of an indentation of the magnetopause in that region. As a result several empirical models consider the surface is indented in that region, while some others do not. To tackle this issue, we fit a total of 17,230 magnetopause crossings to various indented and non-indented analytical models. The results show that while all models describe the magnetopause position and shape equivalently far from the cusp region, the non-indented version over-estimate the radial position of the near-cusp magnetopause. Among indented models, we show that the one designed from non-linearmagneto hydrodynamic simulations fits well the near-cusp magnetopause location, while the other underestimate its position probably because their design was possibly based on magnetopause crossing catalogs that contain cusp inner boundary crossings.

Epithelial to mesenchymal transition (EMT) is a physiological process that assumes a primary role in the induction of cancer metastasis. This results in increased cell renewal, and resistance to cell death and therapies. EMT, therefore, represents an effective strategy for regulating cancerous cell activity. A need for efficacy and low cytotoxicity epithelial to mesenchymal transition modifying drugs has led to the investigational testing of the efficacy of plethora of different groups of phytonutrients. Luteolin is a natural flavonoid inhibits the growth of cancer cells by various mechanisms, such as the stimulation of cancer cell apoptosis, cell cycle arrest, inhibition of cell replication, tumor growth, improvement of drug resistance, prevention of cancer cell intrusiveness and metastasis. This review article focuses on the anti-cancer and anti-metastatic potential of luteolin targeting various transcription factors, markers and signaling pathways associated with the repression of epithelial to mesenchymal transition.

Carotenoids in food substances are believed to have health benefits by lowering the risk of diseases. Lutein, a carotenoid compound, is one of the essential nutrients available in green leafy vegetables (kale, broccoli, spinach, lettuce, and peas), along with other foods, such as eggs. As nutrition plays a pivotal role in maintaining human health, lutein, as a nutritional substance, confers promising benefits against numerous health issues, including neurological disorders, eye diseases, skin irritation, etc. This review describes the in-depth health beneficial effects of lutein. As yet, a minimal amount of literature has been undertaken to consider all its promising bioactivities. The step-by-step biosynthesis of lutein has also been taken into account in this review. Besides, this review demonstrates the drug interactions of lutein with β-carotene, as well as safety concerns and dosage. The potential benefits of lutein have been assessed against neurological disorders, eye diseases, cardiac complications, microbial infections, skin irritation, bone decay, etc. Additionally, recent studies ascertained the significance of lutein nanoformulations in the amelioration of eye disorders, which are also considered in this review. Moreover, a possible approach for the use of lutein in bioactive functional foods will be discussed.

Dipeptidyl peptidase-IV (DPP-IV) inhibitors, often known as gliptins, have been used to treat type 2 diabetes mellitus (T2DM). They may be combined with other medications as an additional treatment or used alone as a monotherapy. In addition to insulin, sulfonylureas, thiazolidinediones, and metformin, these molecules appear as possible therapeutic options. Oxadiazole rings have been employed in numerous different ways during drug development efforts. It has been shown that including them in the pharmacophore increases the amount of ligand that may be bound. The exceptional hydrogen bond acceptor properties of oxadiazoles and the distinct hydrocarbon bonding potential of their regioisomers have been established. Beside their anti-diabetic effects, oxadiazoles display a wide range of pharmacological properties. In this study, we made the assumption that molecules containing oxadiazole rings may afford a different approach to the treatment of diabetes, not only for controlling glycemic levels but also for preventing atherosclerosis progression and other complications associated with diabetes. It was observed that oxadiazole fusion with benzothiazole, 5-(2,5,2-trifluoroethoxy) phenyl, β-homophenylalanine, 2-methyl-2-{5-(4-chlorophenyl), diamine-bridged bis-coumarinyl, 5-aryl-2-(6′-nitrobenzofuran-2′-yl), nitrobenzofuran, and/or oxindole leads to potential anti-diabetic activity.

Extracts from medicinal plants are generally obtained by conventional methods like percolation and maceration. Owing to limitations of traditional methods and to meet the rising demand of extracts, the development of new green approaches is need of hour. In the present research, we have developed an ultrasound-assisted extraction (UAE) method for the Nardostachys jatamansi (NJ) D. Don, DC roots and optimized the extraction parameters for possible improved extract yield. A multivariate optimization strategy using the Centre Composite Design coupled with response surface methodology was applied. A numerical optimization approach accurately predicted the extraction conditions (sonication time ∼ 20 min, ethanol ∼ 70 % and a liquid/solid ratio of about 21:1). Scanning electron microscopy of the plant samples after UAE also indicated the cavitation effect due to sound waves. GC-MS analysis of the optimized ultrasound extract (OUNJ) confirmed improvement in the concentration of various secondary metabolites like jatamansone (91.8 % increase), spirojatamol (42.3 % increase), globulol (130.4 % increase), sitosterol (84.6 % increase) as compared to the soxhlet extract (SXNJ). Different anti-oxidant parameters (DPPH, Glutathione, Catalase SOD and NO) were also significantly altered (p 0.05) in the optimized extracts. The IC

Medicinal plants are considered the reservoir of diverse therapeutic agents and have been traditionally employed worldwide to heal various ailments for several decades. Silymarin is a plant-derived mixture of polyphenolic flavonoids originating from the fruits and akenes of Silybum marianum and contains three flavonolignans, silibinins (silybins), silychristin and silydianin, along with taxifolin. Silybins are the major constituents in silymarin with almost 70–80% abundance and are accountable for most of the observed therapeutic activity. Silymarin has also been acknowledged from the ancient period and is utilized in European and Asian systems of traditional medicine for treating various liver disorders. The contemporary literature reveals that silymarin is employed significantly as a neuroprotective, hepatoprotective, cardioprotective, antioxidant, anti-cancer, anti-diabetic, anti-viral, anti-hypertensive, immunomodulator, anti-inflammatory, photoprotective and detoxification agent by targeting various cellular and molecular pathways, including MAPK, mTOR, β-catenin and Akt, different receptors and growth factors, as well as inhibiting numerous enzymes and the gene expression of several apoptotic proteins and inflammatory cytokines. Therefore, the current review aims to recapitulate and update the existing knowledge regarding the pharmacological potential of silymarin as evidenced by vast cellular, animal, and clinical studies, with a particular emphasis on its mechanisms of action.

During the last few decades, cancer has remained one of the deadliest diseases that endanger human health, emphasizing urgent drug discovery. Cellular senescence has gained a great deal of attention in recent years because of its link to the development of cancer therapy. Senescent cells are incapable of proliferating due to irreversibly inhibition of the initiation of the cell cycle pathways. However, senescent cells aggregate in tissues and produce a pro-inflammatory secretome called senescence-associated secretory phenotype (SASP) that can cause serious harmful effects if not managed properly. There is mounting evidence that senescent cells lead to various phases of tumorigenesis in various anatomical sites, owing mostly to the paracrine activities of the SASP. Therefore, a new treatment field called senotherapeutics has been established. Senotherapeutics are newly developed anticancer agents that have been demonstrated to inhibit cancer efficiently. In light of recent findings, several promising natural products have been identified as senescence inducers and senotherapeutics, including, miliusanes, epigallocatechin gallate, phloretin, silybin, resveratrol, genistein, sulforaphane, quercetin, allicin, fisetin, piperlongumine, berberine, triptolide, tocotrienols and curcumin analogs. Some of them have already been validated through preclinical trials and exert an enormous potential for clinical trials. This review article focuses on and summarizes the latest advances made on cellular senescence and its potential as a target for cancer treatment and highlights the well-known natural products as senescence inducers and senotherapeutics for cancer treatment.

Alzheimer's Disease (AD) is a chronic neurodegenerative disease. It is clinically characterized by memory loss and intellectual decrease, among other neurological deficits. The etiology of AD is not completely understood but includes amyloid plaques and intracellular helical filaments as well as neurofibrillary tangles with hyperphosphorylated tau protein. AD is also associated with alterations in amyloid processing genes, such as PSEN1 or PSEN2 and APP. The modulation of the immune system, cholesterol metabolism, and synaptic vesicle endocytosis have all been shown to remediate AD. In this review, enzymes such as AChE, BuChE, β-secretase, γ-secretase, MAO, and RAGE are discussed as potential targets for AD treatment. The aim of this review was to address the molecular mechanisms as well as various genetic factors in AD etiology. The use of natural compounds against these targets might be beneficial for the management of AD.

Most drugs or the natural substances reputed to display some biological activity are hydrophobic molecules that demonstrate low bioavailability regardless of their mode of absorption. Resveratrol and its derivatives belong to the chemical group of stilbenes; while stilbenes are known to possess very interesting properties, these are limited by their poor aqueous solubility as well as low bioavailability in animals and humans. Among the substances capable of forming nanomolecular inclusion complexes which can be used for drug delivery, cyclodextrins show spectacular physicochemical and biomedical implications in stilbene chemistry for their possible application in nanomedicine. By virtue of their properties, cyclodextrins have also demonstrated their possible use in green chemistry for the synthesis of stilbene glucosylated derivatives with potential applications in dermatology and cosmetics. Compared to chemical synthesis and genetically modified microorganisms, plant cell or tissue systems provide excellent models for obtaining stilbenes in few g/L quantities, making feasible the production of these compounds at a large scale. However, the biosynthesis of stilbenes is only possible in the presence of the so-called elicitor compounds, the most commonly used of which are cyclodextrins. We also report here on the induction of resveratrol production by cyclodextrins or combinatory elicitation with methyljasmonate in plant cell systems as well as the mechanisms by which they are able to trigger a stilbene response. The present article therefore discusses the role of cyclodextrins in stilbene chemistry both at the physicochemical level as well as the biomedical and biotechnological levels, emphasizing the notion of "easy alliance" between these compounds and stilbenes.

Most drugs or the natural substances reputed to display some biological activity are hydrophobic molecules that demonstrate low bioavailability regardless of their mode of absorption. Resveratrol and its derivatives belong to the chemical group of stilbenes; while stilbenes are known to possess very interesting properties, these are limited by their poor aqueous solubility as well as low bioavailability in animals and humans. Among the substances capable of forming nanomolecular inclusion complexes which can be used for drug delivery, cyclodextrins show spectacular physicochemical and biomedical implications in stilbene chemistry for their possible application in nanomedicine. By virtue of their properties, cyclodextrins have also demonstrated their possible use in green chemistry for the synthesis of stilbene glucosylated derivatives with potential applications in dermatology and cosmetics. Compared to chemical synthesis and genetically modified microorganisms, plant cell or tissue systems provide excellent models for obtaining stilbenes in few g/L quantities, making feasible the production of these compounds at a large scale. However, the biosynthesis of stilbenes is only possible in the presence of the so-called elicitor compounds, the most commonly used of which are cyclodextrins. We also report here on the induction of resveratrol production by cyclodextrins or combinatory elicitation with methyljasmonate in plant cell systems as well as the mechanisms by which they are able to trigger a stilbene response. The present article therefore discusses the role of cyclodextrins in stilbene chemistry both at the physico-chemical level as well as the biomedical and biotechnological levels, emphasizing the notion of "easy alliance" between these compounds and stilbenes. Part of this work is the result of an aid to the postdoctoral training and improvement abroad for Dr Adrián Matencio (number 21229/PD/19) and financed by the Fundación Séneca (Región de Murcia, Spain).

Covering: 1976 to 2020. Although constituting a limited chemical family, phytostilbenes represent an emblematic group of molecules among natural compounds. Ever since their discovery as antifungal compounds in plants and their ascribed role in human health and disease, phytostilbenes have never ceased to arouse interest for researchers, leading to a huge development of the literature in this field. Owing to this, the number of references to this class of compounds has reached the tens of thousands. The objective of this article is thus to offer an overview of the different aspects of these compounds through a large bibliography analysis of more than 500 articles. All the aspects regarding phytostilbenes will be covered including their chemistry and biochemistry, regulation of their biosynthesis, biological activities in plants, molecular engineering of stilbene pathways in plants and microbes as well as their biotechnological production by plant cell systems.

Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by the formation of intracellular neurofibrillary tangles (NFTs) and extracellular amyloid plaques. Growing evidence has suggested that AD pathogenesis is not only limited to the neuronal compartment but also strongly interacts with immunological processes in the brain. On the other hand, aggregated and misfolded proteins can bind with pattern recognition receptors located on astroglia and microglia and can in turn induce an innate immune response, characterized by the release of inflammatory mediators, ultimately playing a role in both the severity and the progression of the disease. It has been reported by genome-wide analysis that several genes which elevate the risk for sporadic AD encode for factors controlling the inflammatory response and glial clearance of misfolded proteins. Obesity and systemic inflammation are examples of external factors which may interfere with the immunological mechanisms of the brain and can induce disease progression. In this review, we discussed the mechanisms and essential role of inflammatory signaling pathways in AD pathogenesis. Indeed, interfering with immune processes and modulation of risk factors may lead to future therapeutic or preventive AD approaches.

Glioblastoma multiforme (GBM) is the most common form of brain cancer and one of the most aggressive cancers found in humans. Most of the signs and symptoms of GBM can be mild and slowly aggravated, although other symptoms might demonstrate it as an acute ailment. However, the precise mechanisms of the development of GBM remain unknown. Due to the improvement of molecular pathology, current researches have reported that glioma progression is strongly connected with different types of epigenetic phenomena, such as histone modifications, DNA methylation, chromatin remodeling, and aberrant microRNA. Furthermore, the genes and the proteins that control these alterations have become novel targets for treating glioma because of the reversibility of epigenetic modifications. In some cases, gene mutations including P16, TP53, and EGFR, have been observed in GBM. In contrast, monosomies, including removals of chromosome 10, particularly q23 and q25-26, are considered the standard markers for determining the development and aggressiveness of GBM. Recently, amid the epigenetic therapies, histone deacetylase inhibitors (HDACIs) and DNA methyltransferase inhibitors have been used for treating tumors, either single or combined. Specifically, HDACIs are served as a good choice and deliver a novel pathway to treat GBM. In this review, we focus on the epigenetics of GBM and the consequence of its mutations. We also highlight various treatment approaches, namely gene editing, epigenetic drugs, and microRNAs to combat GBM.

The primary aim of this study was to determine the relationship between soluble sugar levels (sucrose, glucose, or fructose) in yellow lupine embryo axes and the pathogenicity of the hemibiotrophic fungus Fusarium oxysporum f. sp. Schlecht lupini. The first step of this study was to determine the effect of exogenous saccharides on the growth and sporulation of F. oxysporum. The second one focused on estimating the levels of ergosterol as a fungal growth indicator in infected embryo axes cultured in vitro on sugar containing-medium or without it. The third aim of this study was to record the levels of the mycotoxin moniliformin as the most characteristic secondary metabolite of F. oxysporum in the infected embryo axes with the high sugar medium and without it. Additionally, morphometric measurements, i.e., the length and fresh weight of embryo axes, were done. The levels of ergosterol were the highest in infected embryo axes with a sugar deficit. At the same time, significant accumulation of the mycotoxin moniliformin was recorded in those tissues. Furthermore, it was found that the presence of sugars in water agar medium inhibited the sporulation of the pathogenic fungus F. oxysporum in relation to the control (sporulation of the pathogen on medium without sugar), the strongest inhibiting effect was observed in the case of glucose. Infection caused by F. oxysporum significantly limited the growth of embryo axes, but this effect was more visible on infected axes cultured under sugar deficiency than on the ones cultured with soluble sugars. The obtained results thus showed that high sugar levels may lead to reduced production of mycotoxins by F. oxysporum, limiting infection development and fusariosis.

Dripper clogging reduces the performance and service life of a drip irrigation system. The impact of chlorination (1.5 ppm of free chlorine during 1 h application) and pressure flushing (0.18 MPa) on the biofouling of non-pressure-compensating drippers fed by real reclaimed wastewater was studied at lab scale using Optical Coherence Tomography. The effect of these treatments on microbial composition (bacteria and eukaryotes) was also investigated by High-throughput DNA sequencing. Biofouling was mainly observed in inlet, outlet and return areas of the drippers. Chlorination limited biofilm development mainly in the mainstream of the milli-labyrinth channel. It was more efficient when combined with pressure flushing. Moreover, chlorination was more efficient in maintaining the water distribution uniformity. It reduced the bacterial concentration and the diversity of the dripper biofilms compared to the pressure flushing method. This method strongly modified the microbial communities, promoting chlorine-resistant bacteria such asComamonadaceaeorAzospira. Inversely, several bacterial groups were identified as sensitive to chlorination such as Chloroflexi and Planctomycetes. Nevertheless, one month after stopping the treatments the bacterial diversity re-increased and the chlorine-sensitive bacteria such as Chloroflexi phylum and the Saprospiraceae, Spirochaetaceae, Christensenellaceae and Hydrogenophilaceae families re-emerged with the growth of biofouling, highlighting the resilience of the bacteria from drippers. Based on PCoA analyses, the structure of the communities still clustered separately from never-chlorinated drippers, showing that the effect of chlorination was still present one month after stopping the treatment.HighlightsThe fouling of drippers is a bottleneck for drip irrigation using reclaimed wastewaterBiofouling was lowest when chlorination was combined with pressure flushingThe β-Proteobacteria and Firmicutes contain chlorine resistant bacteriaThe decrease of Chloroflexi by chlorination was transitoryThe bacterial community was resilient after the interruption of cleaning events

Alzheimer's disease (AD) is one of the crucial causative factors for progressive dementia. Neuropathologically, AD is characterized by the extracellular accumulation of amyloid beta plaques and intracellular neurofibrillary tangles in cortical and limbic regions of the human brain. The circadian system is one of the many affected physiological processes in AD, the dysfunction of which may reflect in the irregularity of the sleep/wake cycle. The interplay of circadian and sleep disturbances inducing AD progression is bidirectional. Sleep-associated pathological alterations are frequently evident in AD. Understanding the interrelation between circadian disruption and AD may allow for earlier identification of AD pathogenesis as well as better suited approaches and potential therapies to combat dementia. In this article, we examine the existing literature related to the molecular mechanisms of the circadian clock and interacting mechanisms of circadian disruption and AD pathogenesis.

Soluble sugars such as sucrose, glucose and fructose in plant host cells not only play the role as donors of carbon skeletons, but they may also induce metabolic signals influencing the expression of defense genes. These metabolites function in a complex network with many bioactive molecules, which independently or in dialogue, induce successive defense mechanisms. The aim of this study was to determine the involvement of sucrose and monosaccharides as signaling molecules in the regulation of the levels of phytohormones and hydrogen peroxide participating in the defense responses of Lupinus luteus L. to a hemibiotrophic fungus Fusarium oxysporum Schlecht f. sp. lupini. A positive correlation between the level of sugars and postinfection accumulation of salicylic acid and its glucoside, as well as abscisic acid, was noted. The stimulatory effect of sugars on the production of ethylene was also reported. The protective role of soluble sugars in embryo axes of yellow lupine was seen in the limited development of infection and fusariosis. These results provide evidence for the enhanced generation of signaling molecules both by sugar alone as well as during the crosstalk between sugars and infection caused by F. oxysporum. However, a considerable postinfection increase in the level of these signaling molecules under the influence of sugars was recorded. The duration of the postinfection generation of these molecules in yellow lupine was also variable.