Ethanolic extracts from Mangifera indica L. have been proved to possess anti-tumor properties in many cancer systems. However, although most effects have been demonstrated with fruit pulp extract, the underlying molecular mechanisms of mango peel are still unclear. This study was designed to explore the effects of mango peel extract (MPE) on colon cancer cell lines. MPE affected cell viability and inhibited the colony formation trend of tumor cells, while no effects were observed in human dermal fibroblasts used as a non-cancerous cell line model. These events were a consequence of the induction of apoptosis associated to reactive oxygen species (ROS) production, activation of players of the oxidative response such as JNK and ERK1/2, and the increase in Nrf2 and manganese superoxide dismutase (MnSOD). Significantly, mango peel-activated stress triggered a DNA damage response evidenced by the precocious phosphorylation of histone 2AX (γH2AX), as well as phosphorylated Ataxia telangiectasia-mutated (ATM) kinase and p53 upregulation. Mango peel extract was also characterized, and HPLC/MS (High Performance Liquid Chromatography/Mass Spectrometry) analysis unveiled the presence of some phenolic compounds that could be responsible for the anti-cancer effects. Collectively, these findings point out the importance of the genotoxic stress signaling pathway mediated by γH2AX in targeting colon tumor cells to apoptosis.

Niosomes are non-ionic surfactant-based vesicles with high promise for drug delivery applications. They can be rapidly prepared via microfluidics, allowing their reproducible production without the need of a subsequent size reduction step, by controlled mixing of two miscible phases of an organic (lipids dissolved in alcohol) and an aqueous solution in a microchannel. The control of niosome properties and the implementation of more complex functions, however, thus far are largely unknown for this method. Here we investigate microfluidics-based manufacturing of topotecan (TPT)-loaded polyethylene glycolated niosomes (PEGNIO). The flow rate ratio of the organic and aqueous phases was varied and optimized. Furthermore, the surface of TPT-loaded PEGNIO was modified with a tumor homing and penetrating peptide (tLyp-1). The designed nanoparticular drug delivery system composed of PEGNIO-TPT-tLyp-1 was fabricated for the first time via microfluidics in this study. The physicochemical properties were determined through dynamic light scattering (DLS) and zeta potential analysis. In vitro studies of the obtained formulations were performed on human glioblastoma (U87) cells. The results clearly indicated that tLyp-1-functionalized TPT-loaded niosomes could significantly improve anti-glioma treatment.

Prion diseases are fatal neurodegenerative diseases that affect humans and animals. Prion strains, conformational variants of misfolded prion proteins, are associated with distinct clinical and pathological phenotypes. Host-strain interactions result in the selective damage of distinct brain areas and they are responsible for strain selection and/or adaptation, but the underlying molecular mechanisms are unknown. Prion strains can be distinguished by their cell tropism in vivo and in vitro, which suggests that susceptibility to distinct prion strains is determined by cellular factors. The neuroblastoma cell line PK1 is refractory to the prion strain Me7, but highly susceptible to RML. We challenged a large number of clonal PK1 lines with Me7 and successfully selected highly Me7-susceptible subclones (PME) to investigate whether the prion strain repertoire of PK1 can be expanded. Notably, the Me7-infected PME clones were more protease-resistant when compared to RML-infected PME clones, which suggested that cell-adapted Me7 and RML are distinct prion strains. Strikingly, Me7-refractory cells, including PK1 and astrocytes in cortico-hippocampal cultures, are highly susceptible to prions, being derived from homogenates of Me7-infected PME cells, suggesting that the passage of Me7 in PME cells leads to an extended host range. Thus, PME clones represent a compelling cell model for strain selection and adaptation.

Kidney transplantation is the treatment of choice for patients with advanced chronic kidney disease (CKD) and end stage renal disease (ESRD). However, acute rejection (AR) is a common complication in kidney transplantation and is associated with reduced graft survival. Current diagnosis of AR relies mainly on clinical monitoring including serum creatinine, proteinuria, and confirmation by histopathologic assessment in the biopsy specimen of graft kidney. Although an early protocol biopsy is indispensable for depicting the severity of pathologic lesions in subclinical acute rejection (subAR), it is not acceptable in some cases and cannot be performed because of its invasive nature. Therefore, we examined the detection of noninvasive biomarkers that are closely related to the pathology of subAR in protocol biopsies three months after kidney transplantation. In this study, the urinary level of microtubule-associated protein 1 light chain 3 (LC3), monocyte chemotactic protein-1 (MCP-1), liver-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), and human epididymis secretory protein 4 (HE4) were measured three months after kidney transplantation. Urine samples of 80 patients undergoing kidney transplantation between August 2014 to September 2016, were prospectively collected after three months. SubAR was observed in 11 patients (13.8%) in protocol biopsy. The urinary levels of LC3, MCP-1, NGAL, and HE4 were significantly higher in patients with subAR than in those without, while those of L-FABP did not differ between the two groups. Multivariate regression models, receiver-operating characteristics (ROC), and areas under ROC curves (AUC) were used to identify predicted values of subAR. Urinary HE4 levels were able to better identify subAR (AUC = 0.808) than the other four urinary biomarkers. In conclusion, urinary HE4 is increased in kidney transplant recipients of subAR three months after kidney transplantation, suggesting that HE4 has the potential to be used as a novel clinical biomarker for predicting subAR.

Epidermal growth factor receptor (EGFR) is associated with the progression of a wide range of cancers including breast, glioma, lung, and liver cancer. The observation that EGFR inhibition can limit the growth of EGFR positive cancers has led to the development of various EGFR inhibitors including monoclonal antibodies and small-molecule inhibitors. However, the reported toxicity and drug resistance greatly compromised the clinical outcome of such inhibitors. As a type of chemical antibodies, nucleic acid aptamer provides an opportunity to overcome the obstacles faced by current EGFR inhibitors. In this study, we have developed and investigated the therapeutic potential of a 27mer aptamer CL-4RNV616 containing 2'-O-Methyl RNA and DNA nucleotides. Our results showed that CL-4RNV616 not only displayed enhanced stability in human serum, but also effectively recognized and inhibited the proliferation of EGFR positive Huh-7 liver cancer, MDA-MB-231 breast cancer, and U87MG glioblastoma cells, with an IC50 value of 258.9 nM, 413.7 nM, and 567.9 nM, respectively. Furthermore, TUNEL apoptosis assay revealed that CL-4RNV616 efficiently induced apoptosis of cancer cells. In addition, clinical breast cancer biopsy-based immunostaining assay demonstrated that CL-4RNV616 had a comparable detection efficacy for EGFR positive breast cancer with commonly used commercial antibodies. Based on the results, we firmly believe that CL-4RNV616 could be useful in the development of targeted cancer therapeutics and diagnostics.

The main objective of this study is to develop a novel dual-purpose material based on carbon xerogel microspheres (CXMs) that permits the delayed release of cannabidiol (CBD) and the removal of aflatoxin. The CXMs were prepared by the sol-gel method and functionalized with phosphoric acid (CXMP) and melamine (CXMN). The support and the modified materials were characterized by scanning electronic microscopy (SEM), N2 adsorption at -196 °C, X-ray photoelectron spectroscopy (XPS), and zeta potential. For the loading of the cannabidiol (CBD) in the porous samples, batch-mode adsorption experiments at 25 °C were performed, varying the concentration of CBD. The desorption kinetics was performed at two conditions for simulating the gastric (pH of 2.1) and intestinal (pH of 7.4) conditions at 37 °C based on in vitro CBD release. Posteriorly, the samples obtained after desorption were used to study aflatoxin removal, which was evaluated through adsorption experiments at pH = 7.4 and 37 °C. The adsorption isotherms of CBD showed a type I(b) behavior, with the adsorbed uptake being higher for the support than for the modified materials with P and N. Meanwhile, the desorption kinetics of CBD at gastric conditions indicated release values lower than 8%, and the remaining amount was desorbed at pH = 7.4 in three hours until reaching 100% based on the in vitro experiments. The results for aflatoxin showed total removal in less than 30 min for all the materials evaluated. This study opens a broader landscape in which to develop dual-purpose materials for the delayed release of CBD, improving its bioavailability and allowing aflatoxin removal in gastric conditions.

Corilagin (β-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-d-glucose), an ellagitannin, is one of the major bioactive compounds present in various plants. Ellagitannins belong to the hydrolyzable tannins, a group of polyphenols. Corilagin shows broad-spectrum biological, and therapeutic activities, such as antioxidant, anti-inflammatory, hepatoprotective, and antitumor actions. Natural compounds possessing antitumor activities have attracted significant attention for treatment of cancer. Corilagin has shown inhibitory activity against the growth of numerous cancer cells by prompting cell cycle arrest at the G2/M phase and augmented apoptosis. Corilagin-induced apoptosis and autophagic cell death depends on production of intracellular reactive oxygen species in breast cancer cell line. It blocks the activation of both the canonical Smad and non-canonical extracellular-signal-regulated kinase/Akt (protein kinase B) pathways. The potential apoptotic action of corilagin is mediated by altered expression of procaspase-3, procaspase-8, procaspase-9, poly (ADP ribose) polymerase, and Bcl-2 Bax. In nude mice, corilagin suppressed cholangiocarcinoma growth and downregulated the expression of Notch1 and mammalian target of rapamycin. The aim of this review is to summarize the anticancer efficacy of corilagin with an emphasis on the molecular mechanisms involving various signaling pathways in tumor cells.

Two class I family teosinte branched1/cycloidea/proliferating cell factor1 (TCP) proteins from allotetraploid cotton are involved in cotton fiber cell differentiation and elongation and root hair development. However, the biological function of most class II TCP proteins is unclear. This study sought to reveal the characteristics and functions of the sea-island cotton class II TCP gene GbTCP4 by biochemical, genetic, and molecular biology methods. GbTCP4 protein localizes to nuclei, binding two types of TCP-binding cis-acting elements, including the one in its promoter. Expression pattern analysis revealed that GbTCP4 is widely expressed in tissues, with the highest level in flowers. GbTCP4 is expressed at different fiber development stages and has high transcription in fibers beginning at 5 days post anthesis (DPA). GbTCP4 overexpression increases primary root hair length and density and leaf and stem trichomes in transgenic Arabidopsis relative to wild-type plants (WT). GbTCP4 binds directly to the CAPRICE (CPC) promoter, increasing CPC transcript levels in roots and reducing them in leaves. Compared with WT plants, lignin content in the stems of transgenic Arabidopsis overexpressing GbTCP4 increased, and AtCAD5 gene transcript levels increased. These results suggest that GbTCP4 regulates trichome formation and root hair development in Arabidopsis and may be a candidate gene for regulating cotton fiber elongation.

Phthalate acid esters (PAEs) are the most frequently utilized synthetic chemical compounds worldwide. They are typical emergent contaminants and are currently attracting considerable concern due to their risks to plants, animals, and public health. Determining the vital environmental factors that affect the toxicity of target pollutants in soil is important for vegetable production and the maintenance and control of soil productivity. We investigated the influence of di-n-butyl phthalate (DBP) and bis(2-ethylhexyl) phthalate (DEHP) under different soil conditions on physiological changes in water spinach (Ipomoea aquatic Forsk.) seedlings and the rhizosphere soil microbial community. Supported by our former experiments in which we determined the representative concentrations that caused the most pronounced toxic effects, three experimental concentrations were studied including control soils without PAEs and spiked soils with either 20 mg DBP or DEHP kg-1 soil. The soil at all the three PAE concentrations was then adjusted to test two soil pH values, three levels of soil organic matter (SOM) content, and three levels of soil moisture content; thus, we completed 12 treatments or conditions simulating different soil environment conditions in greenhouses. After 30 days of cultivation, we analyzed the toxicity effects of two target PAEs on plant growth and physiological factors, and on soil microbial community characteristics. The toxicity of soil DBP and DEHP to the physiology of water spinach was found to be most affected by the soil pH value, then by SOM content, and least of all by soil moisture. The results of the 454 high-throughput sequencing analysis of the soil microbial community indicated that the toxicity of target PAEs to soil microorganisms was most affected by SOM content and then by soil moisture, and no clear relationship was found with soil pH. Under different soil conditions, declines in leaf biomass, chlorophyll a content, and carotenoid content-as well as increases in free amino acid (FAA) content, superoxide anion free radical activity, and hydroxyl radical activity-occurred in response to DBP or DEHP. Heavy use of chemical fertilizer, organic fertilizer, and high humidity led to the special environmental conditions of greenhouse soil, constituting the main conditions considered in this study. The results indicate that under the special highly intensive production systems of greenhouses, soil conditions may directly influence the effects of pollutant phytotoxicity and may thus endanger the yield, nutrient content, and food safety of vegetables. The combined studies of the impacts on plants and rhizosphere microorganisms give a more detailed picture of the toxic effects of the pollutants under different soil conditions.

Clostridium perfringens toxinotype D, toxinotype E, and gastroenteritis-linked BEC/CPILE-positive strains have never been reported in healthy children. We isolated, whole-genome sequenced and bioinformatically characterised three C. perfringens isolates-type D (IQ1), type E (IQ2) and BEC/CPILE-positive (IQ3), recovered from the stools of three healthy two-year-olds, which were further compared to 128 C. perfringens genomes available from NCBI. The analysis uncovered a previously under-described putative toxin gene alv (alveolysin) encoded by isolates IQ2 and IQ3, which appeared to be a clade-specific trait associated with strains from domestic animals. A plasmid analysis indicated that the iota-toxin was encoded on a near-intact previously described plasmid pCPPB-1 in type E strain IQ2. The BEC genes becA and becB were carried on a near-identical pCPOS-1 plasmid previously associated with Japanese gastroenteritis outbreaks. Furthermore, a close phylogenetic relatedness was inferred between the French C. perfringens type E isolates cp515.17 and newly sequenced IQ2, suggesting geographical links. This study describes novel C. perfringens isolates from healthy individuals which encode important toxin genes, indicating the potential spread of these veterinary and clinically important strains and mobile genetic elements, and highlights areas for future research.

Pediatric human immunodeficiency virus (HIV) care in resource-limited settings remains a major challenge to achieving global HIV treatment and virologic suppression targets, in part because the administration of combination antiretroviral therapies (cART) is inherently complex in this population and because viral load and drug resistance genotyping are not routinely available in these settings. Children may also be at elevated risk of transmission of drug-resistant HIV as a result of suboptimal antiretroviral administration for prevention of mother-to-child transmission. We investigated the prevalence and the correlates of pretreatment HIV drug resistance (PDR) among HIV-infected, cART-naive children in Ethiopia. We observed an overall PDR rate of 14%, where all cases featured resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs): ~9% of participants harbored resistance solely to NNRTIs while ~5% harbored resistance to both NNRTIs and nucleoside reverse transcriptase inhibitors (NRTIs). No resistance to protease inhibitors was observed. No sociodemographic or clinical parameters were significantly associated with PDR, though limited statistical power is noted. The relatively high (14%) rate of NNRTI resistance in cART-naive children supports the use of non-NNRTI-based regimens in first-line pediatric treatment in Ethiopia and underscores the urgent need for access to additional antiretroviral classes in resource-limited settings.

The aim of this study was to investigate the efficacy of the vacuum-assisted biopsy (VAB) system in evacuating symptomatic haematomas after VAB excision of benign breast lesions. We retrospectively analysed the data of eight patients with symptomatic and large haematomas who were treated with VAB evacuation between 10 and 14 days after VAB excision. Only one case underwent the procedure 24 h after VAB excision, due to the patient reporting intense pain, which was relieved after application of the technique, even though it had to be done twice. This new clinical application of the VAB system for evacuating symptomatic breast haematomas was successful in all the cases in the present study. No technique-related complications were observed. Conclusions: To the best of our knowledge, this is the first study to reveal that VAB evacuation of symptomatic haematomas is safe, effective, quick and well-tolerated by patients.

Dendritic cell-based and other vaccination strategies that use the patient's own immune system for the treatment of cancer are gaining momentum. Most studies of therapeutic cancer vaccination have been performed in adults. However, since cancer is one of the leading causes of death among children past infancy in the Western world, the hope is that this form of active specific immunotherapy can play an important role in the pediatric population as well. Since children have more vigorous and adaptable immune systems than adults, therapeutic cancer vaccines are expected to have a better chance of creating protective immunity and preventing cancer recurrence in pediatric patients. Moreover, in contrast to conventional cancer treatments such as chemotherapy, therapeutic cancer vaccines are designed to specifically target tumor cells and not healthy cells or tissues. This reduces the likelihood of side effects, which is an important asset in this vulnerable patient population. In this review, we present an overview of the different therapeutic cancer vaccines that have been studied in the pediatric population, with a main focus on dendritic cell-based strategies. In addition, new approaches that are currently being investigated in clinical trials are discussed to provide guidance for further improvement and optimization of pediatric cancer vaccines.

Many toxic agents can cause DNA double strand breaks (DSBs), which are in most cases quickly repaired by the cellular machinery. Using ionising radiation, we explored the kinetics of DNA lesion signaling and structural chromosome aberration formation at the intra- and inter-chromosomal level. Using a novel approach, the classic Premature Chromosome Condensation (PCC) was combined with γ-H2AX immunofluorescence staining in order to unravel the kinetics of DNA damage signalisation and chromosome repair. We identified an early mechanism of DNA DSB joining that occurs within the first three hours post-irradiation, when dicentric chromosomes and chromosome exchanges are formed. The slower and significant decrease of "deleted chromosomes" and 1 acentric telomere fragments observed until 24 h post-irradiation, leads to the conclusion that a second and error-free repair mechanism occurs. In parallel, we revealed remaining signalling of γ-H2AX foci at the site of chromosome fusion long after the chromosome rearrangement formation. Moreover there is important signalling of foci on the site of telomere and sub-telomere sequences suggesting either a different function of γ-H2AX signalling in these regions or an extreme sensibility of the telomere sequences to DNA damage that remains unrepaired 24 h post-irradiation. In conclusion, chromosome repair happens in two steps, including a last and hardly detectable one because of restoration of the chromosome integrity.

The paper presents the application of natural materials, especially wood, which are relevant for human well-being in built environments of health, social, and day care facilities. These properties were tested by a complex methodology in a case study in the wooden waiting room at National Oncology Institute in Bratislava. In this space, experimental tests of physiological responses were further executed on 50 volunteers moving in the waiting room for 20 min. In this article, the EEG (electroencephalograph) (four persons) and emotions from the faces of all our volunteers before entering and after a stay in a wooden waiting room were recorded. Specifically, the ECG (electrocardiograph), heart rate (HR), and respiration activity were measured by using our own designed ECG holter (40 persons), and also blood pressure and cortisol levels were observed. The usage of wooden materials verifies their regenerative and positive impact on the human nervous system, through the appealing aesthetics (color, texture, and structures), high contact comfort, pleasant smell, possibility to regulate air humidity, volatile organic compound emissions (VOC-emissions), and acoustic well-being in the space.

RNA editing in plant mitochondria and plastids converts specific nucleotides from cytidine (C) to uridine (U). These editing events differ among plant species and are relevant to developmental stages or are impacted by environmental conditions. Proteins of the MORF family are essential components of plant editosomes. One of the members, MORF9, is considered the core protein of the editing complex and is involved in the editing of most sites in chloroplasts. In this study, the phenotypes of a T-DNA insertion line with loss of MORF9 and of the genetic complementation line of Arabidopsis were analyzed, and the editing efficiencies of plastid RNAs in roots, rosette leaves, and flowers from the morf9 mutant and the wild-type (WT) control were compared by bulk-cDNA sequencing. The results showed that most of the known MORF9-associated plastid RNA editing events in rosette leaves and flowers were similarly reduced by morf9 mutation, with the exception that the editing rate of the sites ndhB-872 and psbF-65 declined in the leaves and that of ndhB-586 decreased only in the flowers. In the roots, however, the loss of MORF9 had a much lower effect on overall plastid RNA editing, with nine sites showing no significant editing efficiency change, including accD-794, ndhD-383, psbZ-50, ndhF-290, ndhD-878, matK-706, clpP1-559, rpoA-200, and ndhD-674, which were reduced in the other tissues. Furthermore, we found that during plant aging, MORF9 mRNA level, but not the protein level, was downregulated in senescent leaves. On the basis of these observations, we suggest that MORF9-mediated RNA editing is tissue-dependent and the resultant organelle proteomes are pertinent to the specific tissue functions.

Genomic approaches are opening avenues for understanding all aspects of biological life, especially as they begin to be applied to multiple individuals and populations. However, these approaches typically depend on the availability of a sequenced genome for the species of interest. While the number of genomes being sequenced is exploding, one group that has lagged behind are weeds. Although the power of genomic approaches for weed science has been recognized, what is needed to implement these approaches is unfamiliar to many weed scientists. In this review we attempt to address this problem by providing a primer on genome sequencing and provide examples of how genomics can help answer key questions in weed science such as: (1) Where do agricultural weeds come from; (2) what genes underlie herbicide resistance; and, more speculatively, (3) can we alter weed populations to make them easier to control? This review is intended as an introduction to orient weed scientists who are thinking about initiating genome sequencing projects to better understand weed populations, to highlight recent publications that illustrate the potential for these methods, and to provide direction to key tools and literature that will facilitate the development and execution of weed genomic projects.

To precisely control the emission limit of volatile organic compounds (VOCs) even at trace amounts, reactive nanomaterials of, e.g., carbon are demanded. Particularly, considering the polar/non-polar nature of VOCs, amphiphilic carbon nanomaterials with a huge surface area could act as multipurpose VOC sensors. Here, for the first time, a buckypaper sensor composed of oxygenated amorphous carbon (a-COx)/graphite (G) nanofilaments is developed. Presence of the oxygen-containing groups rises the selectivity of the sensor to polar VOCs, such as ethanol and acetone through formation of hydrogen bonding, affecting the electron withdrawing ability of the group, the hole carrier density, and, thus, the resistivity. On the other hand, the electrostatic interactions between the toluene aromatic ring and the π electrons of the graphitic crystals cause a formation of charge-transfer complexes, which could be the main mechanism of high responsiveness of the sensor towards non-polar toluene. To the best of my knowledge, an amphiphilic carbon nanofilamentous buckypaper has never been reported for gas sensing, and my device sensing polar/non-polar VOCs is state of the art for environmental control.

Zwitterionic polysaccharides (ZPs) have been shown in recent years to display peculiar immunological properties, thus attracting the interest of the carbohydrate research community. To fully elucidate the mechanisms underlying these properties and exploit the potential of this kind of structures, in depth studies are still required. In this context, the preparation of two cationic, an anionic, as well as two zwitterionic tetrasaccharide analogues of the smallest immunogenic structure of Streptococcus pneumoniae type 14 (SP14) capsular polysaccharide are presented. By exploiting a block strategy, the negative charge has been installed on the non-reducing end of the lactose unit of the tetrasaccharide and the positive charge either on the non-reducing end of the lactosamine moiety or on an external linker. These structures have then been tested by competitive ELISA, showing that the structural variations we made do not modify the affinity of the neutral compound to binding to a specific antibody. However, lower efficacies than the natural SP14 compound were observed. The results obtained, although promising, point to the need to further elongate the polysaccharide structure, which is likely too short to cover the entire epitopes.

New strategies are continuously sought for the treatment of skin and wound infections due to increased problems with non-healing wounds. Electrospun nanofiber mats with antibacterial agents as drug delivery systems provide opportunities for the eradication of bacterial infections as well as wound healing. Antibacterial activities of such mats are directly linked with their drug release behavior. Traditional pharmacopoeial drug release testing settings are not always suitable for analyzing the release behavior of fiber mats intended for the local drug delivery. We tested and compared different drug release model systems for the previously characterized electrospun chloramphenicol (CAM)-loaded nanofiber (polycaprolactone (PCL)) and microfiber (PCL in combination with polyethylene oxide) mats with different drug release profiles. Drug release into buffer solution and hydrogel was investigated and drug concentration was determined using either high-performance liquid chromatography, ultraviolet-visible spectrophotometry, or ultraviolet (UV) imaging. The CAM release and its antibacterial effects in disc diffusion assay were assessed by bacterial bioreporters. All tested model systems enabled to study the drug release from electrospun mats. It was found that the release into buffer solution showed larger differences in the drug release rate between differently designed mats compared to the hydrogel release tests. The UV imaging method provided an insight into the interactions with an agarose hydrogel mimicking wound tissue, thus giving us information about early drug release from the mat. Bacterial bioreporters showed clear correlations between the drug release into gel and antibacterial activity of the electrospun CAM-loaded mats.