Notes

Reversal of azole resistance inside Vaginal yeast infections simply by oridonin.
In this study, antioxidant-rich eggplant peel extract was used to obtain a value-added pastry cream. In order to reduce the susceptibility to degradation, microencapsulation of the biologically active compounds from the eggplant peel was first performed. The microencapsulated bioactive compounds powder (MBC) obtained through freeze-drying retained about 94.31% of the anthocyanins present in the extract, was rich in phenolic compounds, and displayed a high antioxidant activity. The purple colored powder was added to the pastry cream in different concentrations (5% and 10%), allowing significant increase of total phenolic content and antioxidant activity, which were rather stable over 72 h of storage under refrigeration conditions. Sensory evaluation indicated that addition of MBC resulted in improved color and overall acceptability of the pastry cream formulation. All pastry cream samples exhibited rheological behavior specific to the weak gel-like structures, with increasing values of storage modulus with MBC addition. The instrumental texture analysis showed that MBC addition to the pastry cream slightly decreased the firmness and improved the chewiness of the samples.Antimicrobial resistance (AMR) is a major concern facing global health today, with the greatest impact in developing countries where the burden of infectious diseases is much higher. The inappropriate prescribing and use of antibiotics are contributory factors to increasing antibiotic resistance. Antimicrobial stewardship programmes (AMS) are implemented to optimise use and promote behavioural change in the use of antimicrobials. AMS programmes have been widely employed and proven to improve antibiotic use in many high-income settings. However, strategies to contain antimicrobial resistance have yet to be successfully implemented in low-resource settings. A recent toolkit for AMS in low- and middle-income countries by the World Health Organisation (WHO) recognizes the importance of local context in the development of AMS programmes. This study employed a bottom-up approach to identify important local determinants of antimicrobial prescribing practices in a low-middle income setting, to inform the development of a local AMS programme. Analysis of prescribing practices and interviews with prescribers highlighted priorities for AMS, which include increasing awareness of antibiotic resistance, development and maintenance of guidelines for antibiotic use, monitoring and surveillance of antibiotic use, ensuring the quality of low-cost generic medicines, and improved laboratory services. The application of an established theoretical model for behaviour change guided the development of specific proposals for AMS. Finally, in a consultation with stakeholders, the feasibility of the plan was explored along with strategies for its implementation. This project provides an example of the design, and proposal for implementation of an AMS plan to improve antibiotic use in hospitals in low-middle income settings.Acinetobacter baumannii (named in honor of the American bacteriologists Paul and Linda Baumann) is a Gram-negative, multidrug-resistant (MDR) pathogen that causes nosocomial infections, especially in intensive care units (ICUs) and immunocompromised patients with central venous catheters. A. baumannii has developed a broad spectrum of antimicrobial resistance, associated with a higher mortality rate among infected patients compared with other non-baumannii species. In terms of clinical impact, resistant strains are associated with increases in both in-hospital length of stay and mortality. A. baumannii can cause a variety of infections; most involve the respiratory tract, especially ventilator-associated pneumonia, but bacteremia and skin wound infections have also been reported, the latter of which has been prominently observed in the context of war-related trauma. Cases of meningitis associated with A. baumannii have been documented. The most common risk factor for the acquisition of MDR A baumannii is previous antibiotic use, following by mechanical ventilation, length of ICU/hospital stay, severity of illness, and use of medical devices. Current efforts focus on addressing all the antimicrobial resistance mechanisms described in A. baumannii, with the objective of identifying the most promising therapeutic scheme. Bacteriophage- and artilysin-based therapeutic approaches have been described as effective, but further research into their clinical use is required.Energetic binders are a research hot-spot, and much emphasis has been placed on their mechanical properties. In this study, propargyl-terminated ethylene oxide-tetrahydrofuran copolymer (PTPET) was synthesized. Then, PTPET and low-molecular-weight ester-terminated glycidyl azide polymer (GAP) were reacted by the click reaction without using catalysts to obtain a polyether polytriazole elastomer. Through tensile tests, where R = 0.5, the tensile strength reached 0.332 MPa, with an elongation at break of 897.1%. Swelling tests were used to measure the cross-linked network and showed that the cross-linked network regularity was reduced as R increased. The same conclusions were confirmed by dynamic mechanical analysis (DMA). In DMA curves, Tg was around -70 to -65 °C, and a small amount of crystallization appeared at between -50 and -30 °C, because locally ordered structures were also present in random copolymers, thereby forming localized crystals. Their thermal performance was tested by Differential Scanning Calorimeter (DSC) and Thermal Gravimetric Analyzer (TG), and the main mass loss occurred at around 350 to 450 °C, which meant that they were stable. In conclusion, the polyether polytriazole elastomer can be used as a binder in a composite propellant.The advent of new technologies in the field of medicine and dentistry is giving improvements that lead the clinicians to have materials and procedures able to improve patients' quality of life. In dentistry, the last digital techniques offer a fully digital computerized workflow that does not include the standard multiple traditional phases. The purpose of this study is to evaluate all clinical trials and clinical randomized trials related to the digital or dental impression technique in prosthetic dentistry trying to give the readers global information about advantages and disadvantages of each procedure. Data collection was conducted in the main scientific search engines, including articles from the last 10 years, in order to obtain results that do not concern obsolete impression techniques. Elsevier, Pubmed and Embase have been screened as sources for performing the research. The results data demonstrated how the working time appears to be improved with digital workflow, but without a significant result (P = 0.72596). The papers have been selected following the Population Intervention Comparison Outcome (PICO) question, which is related to the progress on dental impression materials and technique. The comparison between dentists or practitioners with respect to classic impression procedures, and students open to new device and digital techniques seem to be the key factor on the final impression technique choice. Surely, digital techniques will end up supplanting the analogical ones altogether, improving the quality of oral rehabilitations, the economics of dental practice and also the perception by our patients.The use of biotherapeutics for the treatment of diseases of the central nervous system (CNS) is typically impeded by insufficient transport across the blood-brain barrier. Here, we investigate a strategy to potentially increase the uptake into the CNS of an affibody molecule (ZSYM73) via binding to the transferrin receptor (TfR). ZSYM73 binds monomeric amyloid beta, a peptide involved in Alzheimer's disease pathogenesis, with subnanomolar affinity. We generated a tri-specific fusion protein by genetically linking a single-chain variable fragment of the TfR-binding antibody 8D3 and an albumin-binding domain to the affibody molecule ZSYM73. Simultaneous tri-specific target engagement was confirmed in a biosensor experiment and the affinity for murine TfR was determined to 5 nM. Blockable binding to TfR on endothelial cells was demonstrated using flow cytometry and in a preclinical study we observed increased uptake of the tri-specific fusion protein into the cerebrospinal fluid 24 h after injection.The development of synthetic ways to fabricate nanosized materials with a well-defined shape, narrow-sized distribution, and high stability is of great importance to a rapidly developing area of nanotechnology. Here, we report an unusual reaction between amorphous two-line ferrihydrite and concentrated sulfuric or other mineral and organic acids. Instead of the expected dissolution, we observed the formation of new narrow-distributed brick-red nanoparticles (NPs) of hematite. Different acids produce similar nanoparticles according to scanning (SEM) and transmission electron microscopy (TEM), selected area electron diffraction (SAED), X-ray diffraction (XRD), infrared spectroscopy (FTIR), and energy-dispersive X-ray spectroscopy (EDX). The reaction demonstrates new possibilities for the synthesis of acid-resistant iron oxide nanoparticles and shows a novel pathway for the reaction of iron hydroxide with concentrated acids. The biomedical potential of the fabricated nanoparticles is demonstrated by the functionalization of the particles with polymers, fluorescent labels, and antibodies. Three different applications are demonstrated i) specific targeting of the red blood cells, e.g., for red blood cell (RBC)-hitchhiking; ii) cancer cell targeting in vitro; iii) infrared ex vivo bioimaging. This novel synthesis route may be useful for the development of iron oxide materials for such specificity-demanding applications such as nanosensors, imaging, and therapy.Silicon nanofiber clusters were successfully generated by the irradiation of millisecond pulsed laser light on silicon sludge disposed from wafer back-grinding processes. It was found that the size, intensity, and growing speed of the laser-induced plume varied with the gas pressure, while the size and morphology of the nanofibers were dependent on the laser pulse duration. The generated nanofibers were mainly amorphous with crystalline nanoparticles on their tips. The crystallinity and oxidation degree of the nanofibers depended on the preheating conditions of the silicon sludge. This study demonstrated the possibility of changing silicon waste into functional nanomaterials, which are possibly useful for fabricating high-performance lithium-ion battery electrodes.Nanocomposites based on Au- and SiO2-modified SnO2 were studied as sensitive materials for ethanol and benzene detection in dry (RH = 1%) and humid (RH = 20%) air. Modification of SnO2 by amorphous SiO2 (13 mol.%) was effectuated by hydrothermal synthesis; modification by Au nanoparticles (1 wt.%) was carried out via impregnation by citrate-stabilized Au sol. The composition of the samples was determined by X-ray fluorescent spectroscopy and energy-dispersive X-ray spectroscopy. The microstructure was characterized by XRD, HRTEM, and low-temperature nitrogen adsorption. The surface groups were investigated by XPS, TPR-H2, and FTIR spectroscopy. DRIFT spectroscopy was performed to investigate the interaction between ethanol and the surface of the synthesized materials. Studies of the sensor properties have shown that in all cases the most sensitive is the SnO2/SiO2-Au nanocomposite. This material retains high sensitivity even in a humid atmosphere. The obtained results are discussed in terms of the synergistic effect of two modifiers (Au and SiO2) in the formation of sensor properties of SnO2/SiO2-Au nanocomposites.The synthesis of ribosomes is one of the central and most resource demanding processes in each living cell. As ribosome biogenesis is tightly linked with the regulation of the cell cycle, perturbation of ribosome formation can trigger severe diseases, including cancer. Eukaryotic ribosome biogenesis starts in the nucleolus with pre-rRNA transcription and the initial assembly steps, continues in the nucleoplasm and is finished in the cytoplasm. From start to end, this process is highly dynamic and finished within few minutes. Despite the tremendous progress made during the last decade, the coordination of the individual maturation steps is hard to unravel by a conventional methodology. In recent years small molecular compounds were identified that specifically block either rDNA transcription or distinct steps within the maturation pathway. As these inhibitors diffuse into the cell rapidly and block their target proteins within seconds, they represent excellent tools to investigate ribosome biogenesis. Here we review how the inhibitors affect ribosome biogenesis and discuss how these effects can be interpreted by taking the complex self-regulatory mechanisms of the pathway into account. With this we want to highlight the potential of low molecular weight inhibitors to approach the dynamic nature of the ribosome biogenesis pathway.The objective of this study is to assess the relationship between gallstones and venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), and the risk of VTE after cholecystectomy for gallstones. This nationwide population-based cohort study retrieved the hospitalization database from the Longitudinal Health Insurance Research Database (LHID2000), a database belonging to the National Health Insurance (NHI) program of Taiwan. A total of 345,793 patients aged ≥ 18 years with gallstones diagnosed between 2000 and 2010 were identified as the study cohort. The beneficiaries without gallstones were randomly selected as the control cohort by propensity score matching with the study cohort at a 11 ratio based on age, sex, urbanization, occupation, comorbidities, and year of the index date. We compared the risk of VTE between both cohorts and measured the risk differences of VTE between the gallstones patients with (n = 194,187) and without cholecystectomy (n = 151,606). Each pat, history of pregnancy, and comorbidities (log-rank test, p less then 0.001). Our findings indicate that the risk of DVT or PE in patients with gallstones was greater than those without gallstones. However, the risk of DVT and PE in the patients with gallstones would decrease after cholecystectomy. This area of research needs more studies to ascertain the pathogenesis for the contribution of gallstones to the development of VTE and the protective mechanisms of cholecystectomy against the development of VTE.Several reports have described the anti-cancer activity of arctigenin, a lignan extracted from Arctium lappa L. Here, we investigated the effect of arctigenin (ATG) on doxorubicin (DOX)-induced cell death using MDA-MB-231 human breast cancer cells. The results showed that DOX-induced cell death was enhanced by ATG/DOX co-treatment in a concentration-dependent manner and that this was associated with increased DOX uptake and the suppression of multidrug resistance-associated protein 1 (MRP1) gene expression in MDA-MB-231 cells. ATG enhanced DOX-induced DNA damage and decreased the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and the expressions of RAD51 and survivin. Cell death caused by ATG/DOX co-treatment was mediated by the nuclear translocation of apoptosis inducing factor (AIF), reductions in cellular and mitochondrial Bcl-2 and Bcl-xL, and increases in mitochondrial BAX levels. However, caspase-3 and -7 did not participate in DOX/ATG-induced cell death. We also found that DOX/ATG-induced cell death was linked with activation of the p38 signaling pathway and suppressions of the phosphorylations and expressions of Akt and c-Jun N-terminal kinase. Taken together, these results show that ATG enhances the cytotoxic activity of DOX in MDA-MB-231 human breast cancer cells by inducing prolonged p21 expression and p38-mediated AIF-dependent cell death. In conclusion, our findings suggest that ATG might alleviate the side effects and improve the therapeutic efficacy of DOX.Claudins (CLDNs) play crucial roles in the formation of tight junctions. We have reported that abnormal expression of CLDN2 confers chemoresistance in the spheroids of human lung adenocarcinoma A549 cells. A food composition, which can reduce CLDN2 expression, may function to prevent the malignant progression. Here, we found that ethanol extract of Brazilian green propolis (EBGP) and kaempferide, a major component of EBGP, decrease CLDN2 expression. In the two-dimensional culture model, EBGP decreased the tight junctional localization of CLDN2 without affecting that of zonula occludens-1, an adaptor protein, and enhanced paracellular permeability to doxorubicin, a cytotoxic anticancer drug. EBGP reduced hypoxic stress, and enhanced the accumulation and sensitivity of doxorubicin in the spheroid of A549 cells. Kaempferide dose-dependently decreased CLDN2 expression, although dihydrokaempferide and pinocembrin did not. The phosphorylation of Akt, a regulatory factor of CLDN2 expression, was inhibited by kaempferide but not by dihydrokaempferide. The 2,3-double bond in the C ring may be important to inhibit Akt. Kaempferide decreased the mRNA level and promoter activity of CLDN2, indicating that it inhibits the transcription of CLDN2. In accordance with EBGP, kaempferide decreased the tight junctional localization of CLDN2 and increased a paracellular permeability to doxorubicin, suggesting that it diminished the paracellular barrier to small molecules. In addition, kaempferide reduced hypoxic stress, and enhanced the accumulation and sensitivity of doxorubicin in the spheroids. In contrast, dihydrokaempferide did not improve the sensitivity to doxorubicin. Further study is needed using an animal model, but we suggest that natural foods abundantly containing kaempferide are candidates for the prevention of the chemoresistance of lung adenocarcinoma.Increased hydration is recommended as healthy habit with several merits. However, supportive data are sparse. To assess the efficacy of increased daily water intake, we tested the effect of water supplementation on biomarkers in blood, urine, and saliva. Twenty-four healthy Japanese men and 31 healthy Japanese women with fasting blood glucose levels ranging from 90-125 mg/dL were included. An open-label, two-arm, randomized controlled trial was conducted for 12 weeks. Two additional 550 mL bottles of water on top of habitual fluid intake were consumed in the intervention group. The subjects drank one bottle of water (550 mL) within 2 h of waking, and one bottle (550 mL) 2 h before bedtime. Subjects increased mean fluid intake from 1.3 L/day to 2.0 L/day, without changes in total energy intake. Total body water rate increased with associated water supplementation. There were no significant changes in fasting blood glucose and arginine vasopressin levels, but systolic blood pressure was significantly decreased in the intervention group. Furthermore, water supplementation increased body temperature, reduced blood urea nitrogen concentration, and suppressed estimated glomerular filtration rate reduction. Additionally, existence of an intestinal microbiome correlated with decreased systolic blood pressure and increased body temperature. Habitual water supplementation after waking up and before bedtime in healthy subjects with slightly elevated fasting blood glucose levels is not effective in lowering these levels. However, it represents a safe and promising intervention with the potential for lowering blood pressure, increasing body temperature, diluting blood waste materials, and protecting kidney function. Thus, increasing daily water intake could provide several health benefits.Pathogens hitting the plant cell wall is the first impetus that triggers the phenylpropanoid pathway for plant defense. The phenylpropanoid pathway bifurcates into the production of an enormous array of compounds based on the few intermediates of the shikimate pathway in response to cell wall breaches by pathogens. The whole metabolomic pathway is a complex network regulated by multiple gene families and it exhibits refined regulatory mechanisms at the transcriptional, post-transcriptional, and post-translational levels. The pathway genes are involved in the production of anti-microbial compounds as well as signaling molecules. The engineering in the metabolic pathway has led to a new plant defense system of which various mechanisms have been proposed including salicylic acid and antimicrobial mediated compounds. In recent years, some key players like phenylalanine ammonia lyases (PALs) from the phenylpropanoid pathway are proposed to have broad spectrum disease resistance (BSR) without yield penalties. Now we have more evidence than ever, yet little understanding about the pathway-based genes that orchestrate rapid, coordinated induction of phenylpropanoid defenses in response to microbial attack. It is not astonishing that mutants of pathway regulator genes can show conflicting results. Therefore, precise engineering of the pathway is an interesting strategy to aim at profitably tailored plants. Here, this review portrays the current progress and challenges for phenylpropanoid pathway-based resistance from the current prospective to provide a deeper understanding.Diabetes Mellitus (DM) is a multi-factorial chronic health condition that affects a large part of population and according to the World Health Organization (WHO) the number of adults living with diabetes is expected to increase. Since type 2 diabetes mellitus (T2DM) is suffered by the majority of diabetic patients (around 90-95%) and often the mono-target therapy fails in managing blood glucose levels and the other comorbidities, this review focuses on the potential drugs acting on multi-targets involved in the treatment of this type of diabetes. In particular, the review considers the main systems directly involved in T2DM or involved in diabetes comorbidities. Agonists acting on incretin, glucagon systems, as well as on peroxisome proliferation activated receptors are considered. Inhibitors which target either aldose reductase and tyrosine phosphatase 1B or sodium glucose transporters 1 and 2 are taken into account. Moreover, with a view at the multi-target approaches for T2DM some phytocomplexes are also discussed.Green tea-derived galloylated catechins have weak direct antibacterial activity against both Gram-positive and Gram-negative bacterial pathogens and are able to phenotypically transform, at moderate concentrations, methicillin-resistant Staphylococcus aureus (MRSA) clonal pathogens from full β-lactam resistance (minimum inhibitory concentration 256-512 mg/L) to complete susceptibility (~1 mg/L). Reversible conversion to susceptibility follows intercalation of these compounds into the bacterial cytoplasmic membrane, eliciting dispersal of the proteins associated with continued cell wall peptidoglycan synthesis in the presence of β-lactam antibiotics. The molecules penetrate deep within the hydrophobic core of the lipid palisade to force a reconfiguration of cytoplasmic membrane architecture. The catechin gallate-induced staphylococcal phenotype is complex, reflecting perturbation of an essential bacterial organelle, and includes prevention and inhibition of biofilm formation, disruption of secretion of virulence-related proteins, dissipation of halotolerance, cell wall thickening and cell aggregation and poor separation of daughter cells during cell division. These features are associated with the reduction of capacity of potential pathogens to cause lethal, difficult-to-treat infections and could, in combination with β-lactam agents that have lost therapeutic efficacy due to the emergence of antibiotic resistance, form the basis of a new approach to the treatment of staphylococcal infections.A continuous-flow acetylation reaction was developed, applying cheap and safe reagent, acetonitrile as acetylation agent and alumina as catalyst. The method developed utilizes milder reagent than those used conventionally. The reaction was tested on various aromatic and aliphatic amines with good conversion. The catalyst showed excellent reusability and a scale-up was also carried out. Furthermore, a drug substance (paracetamol) was also synthesized with good conversion and yield.Kinetoplastid parasites, including Leishmania and Trypanosoma spp., are life threatening pathogens with a worldwide distribution. Next-generation therapeutics for treatment are needed as current treatments have limitations, such as toxicity and drug resistance. In this study, we examined the activities of established mammalian target of rapamycin (mTOR)/phosphoinositide 3-kinase (PI3K) inhibitors against these tropical diseases. High-throughput screening of a library of 1742 bioactive compounds against intracellular L. donovani was performed, and seven mTOR/PI3K inhibitors were identified. Dose-dilution assays revealed that these inhibitors had half maximal effective concentration (EC50) values ranging from 0.14 to 13.44 μM for L. donovani amastigotes and from 0.00005 to 8.16 μM for T. brucei. The results of a visceral leishmaniasis mouse model indicated that treatment with Torin2, dactolisib, or NVP-BGT226 resulted in reductions of 35%, 53%, and 54%, respectively, in the numbers of liver parasites. In an acute T. brucei mouse model using NVP-BGT226 parasite numbers were reduced to under the limits of detection by five consecutive days of treatment. Multiple sequence and structural alignment results indicated high similarities between mTOR and kinetoplastid TORs; the inhibitors are predicted to bind in a similar manner. Taken together, these results indicated that the TOR pathways of parasites have potential for the discovery of novel targets and new potent inhibitors.Fibromyalgia syndrome (FMS) is a chronic illness characterized by widespread pain and other clinical and emotional symptoms. The lack of objective markers of the illness has been a persistent problem in FMS research, clinical management, and social recognition of the disease. A critical historical revision of diagnostic criteria for FMS, especially those formulated by the American College of Rheumatology (ACR), was performed. This narrative review has been structured as follows Introduction; historical background of FMS, including studies proposing and revising the diagnostic criteria; the process of development of the ACR FMS diagnostic criteria (1990 and 2010 versions); revisions of the 2010 ACR FMS diagnostic criteria; the development of scales based on the 2010 and 2011 criteria, which could help with diagnosis and evaluation of the clinical severity of the disease, such as the Polysymptomatic Distress Scale and the FMS Survey Questionnaire; relationships of prevalence and sex ratio with the different diagnostic criteria; validity and diagnostic accuracy of the ACR FMS criteria; the issues of differential diagnosis and comorbidity; the strength and main limitations of the ACR FMS criteria; new perspectives regarding FMS diagnosis; and the impact of the novel findings in the diagnosis of FMS. It is concluded that despite the official 2010 FMS diagnostic criteria and the diagnostic proposal of 2011 and 2016, complaints from health professionals and patients continue.RNA-binding proteins (RBPs) are involved in regulating all aspects of RNA metabolism, including processing, transport, translation, and degradation. Dysregulation of RNA metabolism is linked to a plethora of diseases, such as cancer, neurodegenerative diseases, and neuromuscular disorders. Recent years have seen a dramatic shift in the knowledge base, with RNA increasingly being recognised as an attractive target for precision medicine therapies. In this article, we are going to review current RNA-targeted therapies. Furthermore, we will scrutinise a range of drug discoveries targeting protein-RNA interactions. In particular, we will focus on the interplay between Lin28 and let-7, splicing regulatory proteins and survival motor neuron (SMN) pre-mRNA, as well as HuR, Musashi, proteins and their RNA targets. We will highlight the mechanisms RBPs utilise to modulate RNA metabolism and discuss current high-throughput screening strategies. This review provides evidence that we are entering a new era of RNA-targeted medicine.OBJECTIVE The main objective of this study was to evaluate the impact of the French national program on home return of chronic heart failure patients (PRADO-IC) in terms of re-hospitalizations for heart failure (HF) during its deployment in the Bas-Rhin (France). PATIENTS AND METHODS This was a pilot, descriptive, quantitative, retrospective, and bi-centric study (University Hospitals of Strasbourg and Haguenau Hospital Center, France). It included all patients included in the PRADO-IC program from these centers between January 1, 2015 and December 31, 2015. The primary endpoint of our study was the evaluation of the number of 1-year, 6-month, and 30-day re-admissions to the hospital in relation to an acute HF episode, before and after the inclusion of patients in the PRADO-IC program. The secondary endpoints were the number of overall re-hospitalizations (all-cause); the number of days of hospitalization for HF; the time to first re-hospitalization and the average length of hospital stay, before and after in39 ± 15.94 days for the 1 year follow-up (p less then 0.001). In contrast, inclusion in PRADO-IC statistically increased the mean time to first re-hospitalization for HF from mean 99.36 ± 72.39 days before inclusion to 148.11 ± 112.77 days after inclusion (p less then 0.001). CONCLUSION This study seems to demonstrate that the PRADO-IC program could improve the management of chronic HF patients in ambulatory care, particularly regarding HF re-hospitalization. However, due to the limitations of the methodology used and the small number of patients, it is advisable to consolidate its initial results with a randomized controlled study on a larger number of patients. In our opinion, its results need to be communicated because, to our knowledge, no equivalent study exists.The buriti oil (Mauritia flexuosa L.) can be associated with polymeric matrices for biomedical applications. This study aimed to evaluate the effect of chitosan gel (CG) associated with buriti oil (CGB) as a healing agent. The fatty acids and volatile compounds composition of buriti oil were performed and the composite gels were characterized using FTIR and thermal analysis. Biological tests including antimicrobial, antioxidant, anti-inflammatory and healing effects were also investigated. Buriti oil is composed of oleic and palmitic acids, and the main volatile compounds were identified. The buriti oil did not show antimicrobial activity, on the other hand, the composite gel (chitosan and oil) proved to be efficient against Staphylococcus aureus and Klebsiella pneumonia at the 10 mg/mL. Similar behavior was observed for antioxidant activity, determined by the β-carotene bleaching assay, composite gels presenting higher activity and buriti oil showed anti-inflammatory activity, which may be related to the inhibition of the release of free radicals. Regarding wound healing performed using in vivo testing, the composite gel (CGB) was found to promote faster and complete wound retraction. The results indicated that the gel chitosan-buriti oil has a set of properties that improve its antibacterial, antioxidant and healing action, suggesting that this material can be used to treat skin lesions.Homoepitaxial growth of organic semiconductor single crystals is a promising methodology toward the establishment of doping technology for organic opto-electronic applications. In this study, both electronic and crystallographic properties of homoepitaxially grown single crystals of rubrene were accurately examined. Undistorted lattice structures of homoepitaxial rubrene were confirmed by high-resolution analyses of grazing-incidence X-ray diffraction (GIXD) using synchrotron radiation. Upon bulk doping of acceptor molecules into the homoepitaxial single crystals of rubrene, highly sensitive photoelectron yield spectroscopy (PYS) measurements unveiled a transition of the electronic states, from induction of hole states at the valence band maximum at an adequate doping ratio (10 ppm), to disturbance of the valence band itself for excessive ratios (≥ 1000 ppm), probably due to the lattice distortion.Hyponatremia has been shown to be associated with prognosis in various cancers, but its role in upper tract urothelial carcinoma (UTUC) is largely unidentified. We created an international multiregional cohort of UTUC, consisting of 524 and 213 patients from Taiwan and the U.S., to validate the significance of hyponatremia. Clinicopathologic characteristics were compared according to the presence of hyponatremia. Univariate and multivariate Cox regression models were used to investigate the association of hyponatremia with disease progression and survival. The impact of hyponatremia in patients from distinct regions was also analyzed. Hyponatremia was found in 143 (19.4%) patients. Hyponatremic patients had significantly worse Eastern Cooperative Oncology Group (ECOG) performance status (p = 0.00001) and higher pT stage (p = 0.002). In multivariate analysis, hyponatremia was an independent prognostic factor for progression (HR 1.585, 95% CI 1.115-2.253, p = 0.010), cancer-specific death (HR 2.225, 95% CI 1.457-3.397, p = 0.0002), and overall mortality (HR 1.819, 95% CI 1.299-2.545, p = 0.0005). Kaplan-Meier analysis showed the consistent adverse effect of hyponatremia on all outcomes in patients from Taiwan and the U.S. (all p less then 0.05). Hyponatremia is commonly accessible and can serve as a negative marker for both the general health condition and disease severity of UTUC patients. A similar implication of hyponatremia in progression and survival despite patients' region of presentation suggests its general applicability across different ethnicities.Next generation sequencing (NGS) allows parallel sequencing of multiple genes at a very high depth of coverage. The need to analyze a variety of targets for diagnostic/prognostic/predictive purposes requires multi-gene characterization. Multi-gene panels are becoming standard approaches for the molecular analysis of solid lesions. We report a custom-designed 128 multi-gene panel engineered to cover the relevant targets in 22 oncogene/oncosuppressor genes for the analysis of the solid tumors most frequently subjected to routine genotyping. A total of 1695 solid tumors were analyzed for panel validation. The analytical sensitivity is 5%. Analytical validation (i) Accuracy sequencing results obtained using the multi-gene panel are concordant using two different NGS platforms and single-gene approach sequencing (100% of 83 cases); (ii) Precision consistent results are obtained in the samples analyzed twice with the same platform (100% of 20 cases). Clinical validation the frequency of mutations identified in different tumor types is consistent with the published literature. This custom-designed multi-gene panel allows to analyze with high sensitivity and throughput 22 oncogenes/oncosuppressor genes involved in diagnostic/prognostic/predictive characterization of central nervous system tumors, non-small-cell lung carcinomas, colorectal carcinomas, thyroid nodules, pancreatic lesions, melanoma, oral squamous carcinomas and gastrointestinal stromal tumors.DNA damage is well recognized as a critical factor in cancer development and progression. DNA lesions create an abnormal nucleotide or nucleotide fragment, causing a break in one or both chains of the DNA strand. When DNA damage occurs, the possibility of generated mutations increases. Genomic instability is one of the most important factors that lead to cancer development. DNA repair pathways perform the essential role of correcting the DNA lesions that occur from DNA damaging agents or carcinogens, thus maintaining genomic stability. Inefficient DNA repair is a critical driving force behind cancer establishment, progression and evolution. A thorough understanding of DNA repair mechanisms in cancer will allow for better therapeutic intervention. In this review we will discuss the relationship between DNA damage/repair mechanisms and cancer, and how we can target these pathways.Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging zoonotic coronavirus that has a tendency to cause significant healthcare outbreaks among patients with serious comorbidities. We analyzed hospital data from the MERS-CoV outbreak in King Abdulaziz Medical Center, Riyadh, Saudi Arabia, June-August 2015 using the susceptible-exposed-infectious-recovered (SEIR) ward transmission model. The SEIR compartmental model considers several areas within the hospital where transmission occurred. We use a system of ordinary differential equations that incorporates the following units emergency department (ED), out-patient clinic, intensive care unit, and hospital wards, where each area has its own carrying capacity and distinguishes the transmission by three individuals in the hospital patients, health care workers (HCW), or mobile health care workers. The emergency department, as parameterized has a large influence over the epidemic size for both patients and health care workers. Trend of the basic reproduction number (R0), which reached a maximum of 1.39 at the peak of the epidemic and declined to 0.92 towards the end, shows that until added hospital controls are introduced, the outbreak would continue with sustained transmission between wards. Transmission rates where highest in the ED, and mobile HCWs were responsible for large part of the outbreak.Parkinson's disease (PD) is the most common neurodegenerative movement disorder without any objective biomarker available to date. Increasing evidence highlights the critical role of neuroinflammation, including T cell responses, and spreading of aggregated α-synuclein in PD progression. Lymphocyte-activation gene 3 (LAG3) belongs to the immunoglobulin (Ig) superfamily expressed by peripheral immune cells, microglia and neurons and plays a key role in T cell regulation. The role of LAG3 has been extensively investigated in several human cancers, whereas until recently, the role of LAG3 in the central nervous system (CNS) has been largely unknown. Accumulating evidence highlights the potential role of LAG3 in PD pathogenesis, mainly by binding to α-synuclein fibrils and affecting its endocytosis and intercellular transmission, which sheds more light on the connection between immune dysregulation and α-synuclein spreading pathology. Serum and cerebrospinal fluid (CSF) soluble LAG3 (sLAG3) levels have been demonstrated to be potentially associated with PD development and clinical phenotype, suggesting that sLAG3 could represent an emerging PD biomarker. Specific single nucleotide polymorphisms (SNPs) of the LAG3 gene have been also related to PD occurrence especially in the female population, enlightening the pathophysiological background of gender-related PD clinical differences. Given also the ongoing clinical trials investigating various LAG3-targeting strategies in human diseases, new opportunities are being developed for PD treatment research. In this review, we discuss recent preclinical and clinical evidence on the role of LAG3 in PD pathogenesis and biomarker potential, aiming to elucidate its underlying molecular mechanisms.Bone morphogenetic protein 2 (BMP2) is strongly selected in both fat-tailed and thin-tailed sheep and may be a candidate gene for sheep tail type selection. However, the mechanism of action of BMP2 in sheep tail fat deposition remains unclear. This study investigated genetic variation and haplotype combinations of the BMP2 gene in sheep with different tail types, aiming to reveal the molecular mechanism of BMP2 in sheep tail fat deposition. We detected a total of three single nucleotide polymorphisms (SNPs) (g.48401619 T > A, g.48401272 C > A, and g.48401136 C > T) among 533 sheep. The alleles and genotype frequencies of these SNPs were in Hardy-Weinberg equilibrium and showed significant correlations with tail length. Linkage disequilibrium existed between the g.48401272 C > A and g.48401136 C > T sites, where CACT was the predominant genotype. At the cellular level, the expression levels of peroxisome proliferator-activated receptor gamma (PPARγ) and lipoprotein lipase (LPL) were upregulated after BMP2 overexpression; there were significantly higher levels of PPARγ than controls at 0 d and 1 d, and of LPL than controls at 1 d and 7 d. These results indicate that the BMP2 gene may participate in sheep tail fat deposition and could be used for molecular-marker-assisted selection of sheep tail type.Orange byproduct (flavedo and albedo) from juice extraction, was used as raw material for this study. Kinetics of total phenolic and total flavonoid contents and antioxidant activity was experimentally determined during both conventional (agitation at 80 rpm) and ultrasound assisted (at 520 and 790 W/L) aqueous extraction from orange byproduct at 5, 15, and 25 °C. An extraction mathematical model was also developed. Significant increase of biocompounds extraction yields was observed as temperature and acoustic power density increased. Ultrasound assistance allowed higher yields at lower temperatures and shorter times. Yields of total phenolic and total flavonoid contents and antioxidant activity obtained with ultrasound extraction (790 W/L, 25 °C, 3 min) were 29%, 39%, and 197% higher, respectively, than those obtained by conventional extraction. The extraction kinetics curves were properly represented by the Weibull model for both conventional and acoustic extraction (mean relative error lower than 5%). Naringin, neohesperidin, and hesperidin were the main phenolic compounds found in the extracts, followed by ferulic, sinapic, and cuomaric acids. Neohesperidin, hesperidin, coumaric acid, and sinapic acid presented the highest yields, especially when extraction was assisted by ultrasound. Meanwhile, naringin and ferulic acid were extracted in a lesser extent, most likely due to their lipophilic character.ATP-dependent proteases are ubiquitous across all kingdoms of life and are critical to the maintenance of intracellular protein quality control. The enzymatic function of these enzymes requires structural stability under conditions that may drive instability and/or loss of function in potential protein substrates. Thus, these molecular machines must demonstrate greater stability than their substrates in order to ensure continued function in essential quality control networks. We report here a role for ATP in the stabilization of the inner membrane YME1L protease. Qualitative fluorescence data derived from protein unfolding experiments with urea reveal non-standard protein unfolding behavior that is dependent on [ATP]. Using multiple fluorophore systems, stopped-flow fluorescence experiments demonstrate a depletion of the native YME1L ensemble by urea-dependent unfolding and formation of a non-native conformation. Additional stopped-flow fluorescence experiments based on nucleotide binding and unfoldase activities predict that unfolding yields significant loss of active YME1L hexamers from the starting ensemble. Taken together, these data clearly define the stress limits of an important mitochondrial protease.Nanoparticles represent a potent antigen presentation and delivery system to elicit an optimal immune response by effector cells targeting tumor-associated antigens expressed by cancer cells. Many types of nanoparticles have been developed, such as polymeric complexes, liposomes, micelles and protein-based structures such as virus like particles. All of them show promising results for immunotherapy approaches. In particular, the immunogenicity of peptide-based cancer vaccines can be significantly potentiated by nanoparticles. Indeed, nanoparticles are able to enhance the targeting of antigen-presenting cells (APCs) and trigger cytokine production for optimal T cell response. The present review summarizes the categories of nanoparticles and peptide cancer vaccines which are currently under pre-clinical evaluation.Genetically edited food utilizes new techniques that may decrease all of the risks associated with genetically modified food, or "GMO" food. Safety and labeling regulations for genetically edited food are still new, and it is challenging for the consumer to differentiate it from conventional food. Although genetically edited food has the potential for reducing the risks associated with the gene introduction process, consumer perceptions toward it are still unclear. The research has compared the regulations governing GMO food and genetically edited food in Japan, Europe, and the United States. We found that the genetically edited food regulations in Japan are the most science-based, in the meaning that genetically edited food products are allowed to be sold without any safety evaluation. Based on the difference among regions, we further studied the potential acceptance level for such products among Japanese consumers, where regulation seemed science-based as policy. To understand the factors that may affect the adoption of genetically edited food among youth in Japan, we utilized the structural equation modeling (SEM) method with 180 surveys of Japanese university students to measure six factors Knowledge, Attitude Towards Technology, Perceived Benefits, Perceived Risks, Trust, and Willingness to Purchase. The survey was conducted twice with an intervention in the middle to measure the effect of science communication, and we found significant differences when comparing the two datasets. The results of this survey indicate the importance of increasing knowledge and the positive role of science communication in increasing the adoption and trust of biotechnology products, such as genetically edited food.Lithium chloride (LiCl) is a widely used drug for the treatment of bipolar disorders, but as a side effect, 40% of the patients develop diabetes insipidus. LiCl affects the activity of the glycogen synthase kinase 3 (GSK3), and mice deficient for GSK3β showed a reduction in the urine concentration capability. The cellular and molecular mechanisms are not fully understood. We used primary cultured inner medullary collecting duct cells to analyze the underlying mechanisms. LiCl and the inhibitor of GSK3 (SB216763) induced a decrease in the aquaporin-2 (Aqp2) protein level. LiCl induced downregulation of Aqp2 mRNA expression while SB216763 had no effect and TWS119 led to increase in expression. The inhibition of the lysosomal activity with bafilomycin or chloroquine prevented both LiCl- and SB216763-mediated downregulation of Aqp2 protein expression. Bafilomycin and chloroquine induced the accumulation of Aqp2 in lysosomal structures, which was prevented in cells treated with dibutyryl cyclic adenosine monophosphate (dbcAMP), which led to phosphorylation and membrane localization of Aqp2. Downregulation of Aqp2 was also evident when LiCl was applied together with dbcAMP, and dbcAMP prevented the SB216763-induced downregulation. We showed that LiCl and SB216763 induce downregulation of Aqp2 via different mechanisms. While LiCl also affected the mRNA level, SB216763 induced lysosmal degradation. Specific GSK3β inhibition had an opposite effect, indicating a more complex regulatory mechanism.The paper presents tools to model low speed airflow coming from a turbulent machine. This low speed flow have instabilities who generate noise disturbances in the environment. The aim of the study proposed in this paper, is the using of cyclostationary tools with audio signals to model this airflow and detect the noisy frequencies to eliminate this noise. This paper also deals with the extraction in real time of the frequency corresponding to the noise nuisance. This extraction makes it possible to build a software sensor. This software sensor can be used to estimate the air flow rate and also to control a future actuator which will reduce the intensity of the noise nuisance. This paper focuses on the characteristic of the sound signal (property of cyclostationarity) and on the development of a software sensor. The results are established using an experimental setup representative of the physical phenomenon to be characterised.Given the concern regarding increased hearing loss in young people who use personal listening devices (PLDs), the present study analyzes the experience of PLDs among college students to identify their knowledge of and attitude toward hearing conservation. It also explains their relationship between knowledge of hearing loss and attitude-related hearing conservation as a questionnaire response using a regression model. A total of 1009 Korean college students responded to an online questionnaire. As a survey tool, the Personal Listening Device and Hearing Questionnaire was adapted as a Korean version with 78 modified items under 9 categories. Using principal component analysis, specific factors were extracted, and their relationships and paths were confirmed using multiple regression analysis. The results of the knowledge category of the questionnaire indicate that most respondents knew how to maintain healthy hearing and understood the signs of hearing loss. Regardless, many college students habitually use PLDs at high levels in noisy environments; they do not recognize how to prevent hearing loss. Even though they continue their current use pattern for PLDs, they also had a positive attitude toward receiving more information about hearing conservation. According to the regression model, the students' self-reported hearing deficits were due to the volume rather than the frequent use. Interestingly, knowledge about hearing loss may encourage students to develop a positive attitude toward reasonable restriction of PLD use. When PLD users have detailed knowledge about the hearing loss provided by professionals, we believe that most will avoid serious hearing problems and its risks and maintain a judicious attitude toward their own conservation.Melanoma is the most serious type of skin cancer and remains highly drug-resistant. Therefore, the discovery of novel effective agents against melanoma is in high demand. Herein, we investigated the cytotoxic activities in melanoma cells and underlying molecular mechanisms of beauvericin (BEA) and its analogue beauvericin G1 (BEA G1), which are cyclohexadepsipeptides isolated from fungi. BEA and BEA G1 significantly suppressed the growth, clonogenicity, migration, and invasion of A375SM human melanoma cells and promoted caspase-dependent apoptosis through upregulation of death receptors, as well as modulation of pro- and anti-apoptotic Bcl-2 family members. Furthermore, the effects of BEA and BEA G1 were associated with the suppression of multiple molecular targets that play crucial roles in melanoma oncogenesis, including ERK, JNK, p38, NF-κB, STAT3, and MITF. Notably, the cytotoxic efficacy of BEA G1 against A375SM cells was stronger than that of BEA. These findings suggest that BEA and BEA G1 can be further investigated as potent cytotoxic natural compounds for the suppression of melanoma progression.
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