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Antimicrobial nonwovens for single use applications (e.g., diapers, sanitary napkins, medical gauze, etc.) are of utmost importance as the first line of defense against bacterial infections. However, the utilization of petrochemical nondegradable polymers in such nonwovens creates sustainability-related issues. Here, sustainable poly(hydroxybutyrate) (PHB) and e-poly-l-lysine (e-PLL) submicro- and microfiber-based antimicrobial nonwovens produced by a novel industrially scalable process, solution blowing, have been proposed. In such nonwovens, e-PLL acts as an active material. In particular, it was found that most of e-PLL is released within the first hour of deployment, as is desirable for the applications of interest. The submicro- and microfiber mat was tested against C. albicans and E. coli, and it was found that e-PLL-releasing microfibers result in a significant reduction of bacterial colonies. It was also found that e-PLL-releasing antimicrobial submicro- and microfiber nonwovens are safe for human cells in fibroblast culture. Mechanical characterization of these nonwovens revealed that, even though they are felt as soft and malleable, they possess sufficient strength, which is desirable in the end-user applications.

In this study we investigated the in vivo Hepatoprotective activity of ethanolic extract of Garuga pinnata (EEGP) leaves in Carbon tetrachloride (CCl4) induced hepatotoxicity using wistar rats of either sex as model. Hepatotoxicity was induced by the administration of CCl4 intraperitoneally (0.125ml CCl4 in liquid paraffin (1:1) per 100g body weight). Garuga pinnata leaves extract at different dose levels (200 and 400mg/kg, p.o.) showed the dose dependant hepatoprotective effect and was compared with well known standard hepatoprotective Silymarain (100mg/kg). When groups were treated with CCl4, significant increase in serum biochemical parameters such as Serum Glutamate Oxaloacetate Transaminase (SGOT), Serum Glutamate Pyruvate Transaminase (SGPT), Alkaline phosphate (ALP), Acid Phosphate (ACP), Creatinine and alteration of tissue biochemical parameters such as reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (LPO), and the total proteins were observed. The histopathological examination of the CCl4 treated groups showed sinusoidal congestion, centrilobular necrosis, marked vacuolations and congestion. However, pretreatment with extract of leaves of Garuga pinnata significantly reduced the increased serum levels of biochemical parameters and restored antioxidant defense enzymes level to its normal. Moreover, histopathology of leaves extract treated groups showed normal architecture with minimal sinusoidal congestion. Taken together, our study concludes that EEGP to be a more potential agent for caring liver from CCl4 induced damage.

The extracts and the compounds isolated from Phyllanthus amarus Schumm and Thonn (Family: Euphorbiaceae) have shown a wide spectrum of pharmacological activities including antiviral, antibacterial, antiplasmodial, antimalarial, antimicrobial, anticancer, antidiabetic, hypolipidemic, antioxidant, hepatoprotective, nephroprotective and diurectic properties. Background: This investigation was aimed at exploring the anxiolytic potential of Phyllanthus amarus standardized extracts and predict probable role of marker phyto constitutents. Objective and Methods: Three standardized extracts of Phyllanthus amarus plant viz. standardized aqueous extract of Phyllanthus amarus whole plant (PAAE), standardized methanolic extract of P. amarus leaf (PAME) and the standardized hydro-methanolic extract of P. amarus leaf (PAHME) were tested in the classical animal models of anxiety: Elevated plus-maze model and Light & Dark Exploration test. Results: The lower doses of the tannin rich extract (PAHME) of the P. amarus possess significant anxiolytic activity compared to lignin rich (PAME) and aqueous extracts (PAAE), while at a higher dose (400mg/kg) the results of all three extracts appears to be potentially sedative. While the molecular docking studies support these probable anxiolytic, the sedative effects of the Phyllanthus amarus extracts could be due to the interaction of tannins and lignans with the GABAbenzodiazepine receptor complex. Conclusion: The results of the present study indicate that the tannin-rich extract of the P. amarus may have potential clinical applications in the management of anxiety. It can be further studied for optimum dosage to be used as a future of anti-anxiety drug development or as a standardized Phytomedicine.

Rabbit and porcine corneas have been used in scientific research due to their structural similarity to the human cornea. Currently, there are no studies that have compared corneal collagen fibrillar diameter, interfibrillar distance and interlamellar distance between human and animal models. Ten pairs of porcine, rabbit, and human corneas were used. These were analysed using light and Transmission Electron microscopy. The collagen fibrillar diameter, interfibrillar distance and interlamellar distance were statistically compared between porcine, rabbit and human corneas. The human, porcine and rabbit; mean collagen fibrillar diameters were: 24.52 ± 2.09 nm; 32.87 ± 0.87 nm; and 33.67 ± 1.97 nm. The mean interfibrillar distances were: 46.10 ± 2.44 nm; 53.33 ± 2.24 nm; and 52.87 ± 2.73 nm, respectively. The collagen fibrillar diameter and interfibrillar distance of porcine and rabbit corneas were significantly different (p

Background:: Phyllanthus fraternus Webster Linn (family, Euphorbiaceae) is used as a traditional medication for the treatment of various disorders and has therapeutic implications. Objective:: This study intends to investigate the anxiolytic potential of Phyllanthus fraternus standardized extract and prediction of the probable role of its marker phytoconstituents. Methods:: We tested the standardized hydro-ethanolic extract of Phyllanthus fraternus (whole plant) for the Elevated plus-maze model (EPM) and Light & Dark Exploration test as classical models for anxiety. Phyto-chemical HPTLC fingerprint analysis was performed for the detection of two classes of compounds lignans and tannins. HPTLC analysis of the standardized extract was performed using phyllanthin hypophyllanthin and corilagin as marker compounds. Additionally, GABA receptor antagonism was studied in other sets of experiments to assess the involvement of this receptor in the anxiolytic- like effects produced by Phyllanthus fraternus. Results:: The lower doses of the lignan and tannin-rich extract of the Phyllanthus fraternus possess significant anxiolytic-like activity compared to the standard diazepam. Additionally, the results of the present study suggested that high doses (400mg/kg) of Phyllanthus fraternus have exerted some sedative- like effects. Phytochemical screening and HPTLC fingerprint analysis indicate the presence of lignans and tannins, whereas HPLC analysis of the standardized extract revealed the presence of marker lignan (Hypophyllanthin) and Tannin (Corilagin). The anxiolytic-like effect of Phyllanthus fraternus observed in the mice models were blocked by Flumazenil indicating the involvement of GABAA receptors in the modulation of this effect. Our molecular docking studies also supported probable anxiolytic and sedative effects. Conclusion:: To summarize, results support the use of Phyllanthus fraternus in the anxiety-like symptoms/ disease condition and suggest its anxiolytic-like effect governed by the GABA-A receptors.

Keratin constitutes the major component of the feather, hair, hooves, horns, and wool represents a group of biological material having high cysteine content (7–13%) as compared to other structural proteins. Keratin -based biomaterials have been investigated extensively over the past few decades due to their intrinsic biological properties and excellent biocompatibility. Unlike other natural polymers such as starch, collagen, chitosan, the complex three-dimensional structure of keratin requires the use of harsh chemical conditions for their dissolution and extraction. The most commonly used methods for keratin extraction are oxidation, reduction, steam explosion, microbial method, microwave irradiation and use of ionic liquids. Keratin -based materials have been used extensively for various biomedical applications such as drug delivery, wound healing, tissue engineering. This review covers the structure, properties, history of keratin research, methods of extraction and some recent advancements related to the use of keratin derived biomaterials in the form of a 3-D scaffold, films, fibers, and hydrogels., Graphical abstract Image 1, Highlights • Keratin a versatile material having unique structural moiety. • Keratin sources and methods of extraction. • Keratin-based materials for biomedical applications. • 3-D scaffold, films, fibers, and hydrogels.

Already in early 2000s, concerns have been growing in the EU about increasing use of cocaine and it is estimated that below 1 % of the population administer the drug by smoking crack cocaine. New available data suggests an increase in the use of crack cocaine and an increase in the number of crack cocaine users entering treatment has been reported in several European countries. Robust estimations of crack cocaine use are however not available yet. The use of crack cocaine has long been associated with severe adverse socio-economic conditions as well as mental health problems, such as suicide ideation and depression. The aim of this study was to assess spatial trends in population-normalized mass loads of crack cocaine biomarkers (i.e., anhydroecgonine and anhydroecgonine methyl ester) in 13 European cities in six countries (the Netherlands, Belgium, Ireland, Portugal, Spain and Italy). Furthermore, temporal trends over a five-year period were evaluated through the analysis of historic samples collected in the Netherlands. Finally, the stability of the crack cocaine biomarkers in wastewater was investigated through batch experiments. The samples were analyzed with a new developed and validated hydrophilic interaction liquid chromatography coupled to mass spectrometry method. Targeted crack cocaine biomarkers were found in all cities. Also, crack cocaine biomarker was detected in wastewater from 2017 to 2021 in the Netherlands, but no significance between the years were found. With respect to biomarker in-sample stability, AEME was found to be stable in wastewater. This study assessed crack cocaine use for the first time on a broad scale, both temporal and in cities across Europe, with wastewater-based epidemiology and it shows the importance of wastewater analysis to monitor community loads of crack cocaine use.

The aim of present work was to develop carboxymethylcellulose (CMC)-polyvinyl alcohol (PVA) hydrogel films for extended delivery of water soluble basic drug, using citric acid (CA) as a cheap and non-toxic crosslinking agent. Gentamicin sulfate (GTM) was used as a model drug. The hydrogel films were evaluated for carboxyl content, tensile strength, swellability, drug loading and release, hemocompatibility and characterized by 13C-CP-MAS NMR, ATR-FTIR and thermal analysis (TGA and DSC). The instrumental analysis helped to confirm the formation of ester crosslinks. CMC-PVA hydrogel films exhibited greater carboxyl content, tensile strength and swellability than the pure CMC hydrogel films. The GTM loading increased with an increase in the amount of PVA in the hydrogel films. The CMC-PVA hydrogel films showed propensity to extend the release of GTM above 24 h. Hemolysis assay revealed the hemocompatible nature of the hydrogel films. Altogether, the CMC-PVA hydrogel films can be envisioned as promising biomaterial for the delivery of water soluble basic drugs.

The search for new antibacterial agents and a better comprehension of substances with antimicrobial behavior is mandatory nowadays due to the serious public health problem of infection diseases. In the present work, 30 diterpenes were studied, with 2 natural derivatives, named ent-16-kauren-19-oic acid and ent-pimara-8(14),15-dien-19-oic acid, and 28 semi-synthetic derivatives. The natural diterpenes were isolated from Mikania glomerata and Viguiera arenaria, respectively. All diterpenes were submitted to antimicrobial assays against six different Gram-positive microorganisms to better understand the structure–activity relationship of antimicrobial diterpenes. The semi-synthetic derivatives were all obtained from the two natural derivatives by structural modifications, mainly esterification reactions. Both natural derivatives, together with the derivative ent-8(14)-pimaren-19-oic acid, displayed the most relevant antibacterial activities, with minimal inhibitory concentration (MIC) values that were less than 10 μg mL–1 for most pathogens; thus, they were considered promising antimicrobial agents. Moreover, in light of the hypothesis of Urzúa and colleagues, several considerations about the structure–activity relationship of antimicrobial diterpenes could be stated.

The extraction of total phenolics (TPC), total flavonoids content (TFC), total saponins content (TSC), and caffeic acid (AC) contents of asparagus roots extract (ARE) from New Zealand and Chinese AR cultivars was optimized following a microwave-assisted extraction combined with central composite design. The determination of AC was conducted by HPLC in samples extracted under the optimum extraction conditions. The optimal variables for ethanol extraction generated a maximum TPC, TFC and TSC of optimal results for 68.6 mg GAE/g, 11.9 mg RE/g and 0.7 mg SE/g as well as antioxidant power towards β-carotene bleaching assay (%βsc) (57.2%), superoxide anion radical (%O sc 2− ) scavenging capacity (20.1%) and ferric reducing antioxidant power assay (FRAP) (1.63 µmol/g). For methanol, optimum extraction conditions obtained maximum TPC (62.6 mg GAE/g) TFC (10.7 mg RE/g), TSC (0.68 mg SE/g) with %βsc (53.9%), %O sc 2− (19.1%) and FRAP (0.63 µmol/g). The content of caffeic acid from ARE ranged from 0.46 to 2.89 mg/g with ethanol and from 0.41 to 2.64 mg/g with methanol.

New porphyrin&ndash, pyrrolidine/pyrroline conjugates were prepared by revisiting 1,3-dipolar cycloaddition reactions between a porphyrinic azomethine ylide and a series of dipolarophiles. Cationic conjugates obtained by alkylation of the pyrrolidine/pyrroline cycloadducts showed ability to generate singlet oxygen and to produce iodine in presence of KI when irradiated with visible light. Some of the cationic derivatives showed photobactericidal properties towards a Gram-negative bioluminescent E. coli. In all cases, these features were significantly improved using KI as coadjutant, allowing, under the tested conditions, the photoinactivation of the bacterium until the detection limit of the method with a drastic reduction of the required photosensitizer concentration and irradiation time. The obtained results showed a high correlation between the ability of the cationic porphyrin derivative to produce singlet oxygen and iodine and its E. coli photoinactivation profile.

Rationale Although dihydrobenzofuran neolignans (DBNs) display a wide diversity of biological activities, the identification of their in vivo metabolites using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) remains a challenge to be overcome. Recently, ESI-MS/MS data of protonated DBNs have been reported, but they were shown to be limited due to the scarcity of diagnostic ions. Methods The gas-phase fragmentation pathways of a series of biologically active synthetic benzofuran neolignans (BNs) and DBNs were elucidated by means of negative ESI accurate-mass tandem and sequential mass spectrometry, and thermochemical data estimated using computational chemistry and the B3LYP/6-31+G(d,p) model. Results Deprotonated DBNs produced more diagnostic product ions than the corresponding protonated molecules. Moreover, a series of odd-electron product ions (radical anions) were detected, which has not been reported for protonated DBNs. Direct C2 H3 O2 • elimination from the precursor ion (deprotonated molecule) only occurred for the BNs and can help to distinguish these compounds from the DBNs. The mechanism through which the [M - H - CH3 OH]- ion is formed is strongly dependent on specific structural features. Conclusions The negative ion mode provides much more information than the positive ion mode (at least one diagnostic product ion was detected for all the analyzed compounds) and does not require the use of additives to produce the precursor ions (deprotonated molecules).

Reconstituted keratin is a novel bone graft material when prepared as a rigid scaffold. Understanding the immunogenicity of this material is important to determine whether this substance is a viable surgical option. Previous studies have shown no innate immune system activation in response to reconstituted keratin implants. To examine antibody-mediated immune responses to reconstituted keratin implants, bone and blood samples were taken from twelve sheep with surgically created tibial defects containing such implants. RT-PCR was used to detect mRNA of the inflammatory marker SOCS 3 in local bony tissue, and a novel immunohistochemistry assay developed to detect antikeratin antibodies in serum. Two animals were sacrificed per time-point at weeks 1, 2, 4, 6, 8 and 12. Time points for serum analysis included baseline (pre-surgery) and all other time points; mRNA analysis examined samples from all time points. No upregulation in antikeratin antibodies or SOCS 3 mRNA was observed at any time point, indicating that reconstituted keratin implants do not trigger an adaptive immune response in vivo in an ovine model. These findings provide the platform for further development of keratin implants in other mammalian models to define its immunogenic profile and safety.

This study elucidates the gas-phase fragmentation pathways of a series of biologically active benzofuran neolignans (BNs) and dihydrobenzofuran neolignans (DBNs) by means of electrospray ionization accurate-mass tandem and sequential mass spectrometry (ESI-MS/MS and ESI-MSn) and thermochemical data estimated by using Computational Chemistry and the B3LYP/6-31+G(d,p) model. In their deprotonated forms, these compounds produced more diagnostic product ions as compared to the corresponding protonated molecules. Moreover, a series of odd-electron product ions (radical anions) were detected, which has not been reported for protonated DBNs. Direct C2H3O2• elimination from the precursor ion (deprotonated molecule) only occurred for the BNs and can help to distinguish these compounds from the DBNs. Although the product ion [M‒CH3OH]‒ emerged in the spectrum of all the DBNs analyzed here, the mechanism through which this ion originates strongly depends on specific structural features, so that further [M‒CH3OH]‒ fragmentation generates important diagnostic product ions. Comparison between the ESI-MS/MS data of these compounds in the negative ion mode (deprotonated molecule) and in the positive ion mode (protonated molecule) revealed that the negative ion mode provides much more information (at least one diagnostic product ion emerged for all the analyzed compounds) and does not require the use of additives to produce the precursor ions (deprotonated molecules).

Hydroxyapatite (HA) derived from bovine bones garnered wider interest as a bone substitute due to their abundant availability as meat wastes and similarities in morphology and mineral composition to human bone. In our previous work, we developed an easy and reproducible method to prepare xenograft HA scaffolds from NZ bovine cancellous bones (BHA). However, the processing methodology rendered the material mechanically weak. The present study investigated the infiltration of chitosan (CS) into the bovine HA scaffolds (CSHA) to improve the mechanical properties of BHA. The presence of characteristic functional groups of HA and CS as detected by infrared spectroscopy confirmed the infiltration of CS into the BHA scaffolds. X-ray Diffraction study confirmed the presence of the hydroxyapatite phase in both BHA and CSHA scaffolds. SEM and μCT analyses showed the CSHA scaffolds presented adequate porosity and an interconnected porous architecture required for cell migration and attachment. CSHA scaffolds presented good thermal, chemical and structural stability while demonstrating sustained biodegradability in simulated body fluid. CSHA scaffolds presented mechanical properties significantly higher than the BHA scaffolds. CSHA scaffolds were biocompatible with Saos-2 osteoblast cells and supported cell proliferation significantly better than the BHA scaffolds indicating their potential in bone tissue engineering.

The synthesis of new porphyrin-indazole hybrids by a Knoevenagel condensation of 2-formyl-5,10,15,20-tetraphenylporphyrin and N-methyl-nitroindazolylacetonitrile derivatives is reported. The target compounds were isolated in moderate to good yields (32–57%) and some of the isolated porphyrin-indazole conjugates showed good performance in the generation of singlet oxygen when irradiated with visible light. Their efficiency as photosensitizers in the photoinactivation of methicillin resistant Staphylococcus aureus–MRSA was evaluated. All derivatives showed to be able to photoinactivate the MRSA bacteria. Compound 3a appears to be the most promising photosensitiser (PS) in the photoinactivation of these bacteria, despite being the least efficient in singlet oxygen generation. The addition of potassium iodide (KI) significantly potentiated the antimicrobial Photodynamic Therapy (aPDT) process mediated by all the analysed porphyrin-indazole conjugates. The combined action of nitroindazole-porphyrins with potassium iodide (KI) action appears to be promising in the photoinactivation of MRSA.

Photodynamic inactivation (PDI) is a therapeutic approach in study due to the ability to reduce or completely eliminate the bacterial strains without the development of resistance mechanisms. In this therapeutic methodology the cationic chlorins (Chls) with pyridinium or inverted pyridinium moieties are one of the photosensitizers exploited in our biological approaches. In this context, we synthesized and characterized new free-base and zinc(II) complexes of pyridinium or inverted pyridinium Chl derivatives (1b, 2, 2a and 2b, respectively) for the inactivation of Escherichia coli (E. coli). The PDI assay was performed with white light irradiation delivered at a fluence rate of 25 mW cm−2. The obtained results of this study demonstrate high PDI efficiency of the zinc(II) metallated Chl 1b, reaching the detection limit of the bioluminescent method (5.2 log reduction) in 45 min of irradiation.

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Background and aims Wastewater‐based epidemiology is an additional indicator of drug use that is gaining reliability to complement the current established panel of indicators. The aims of this study were to: (i) assess spatial and temporal trends of population‐normalized mass loads of benzoylecgonine, amphetamine, methamphetamine and 3,4‐methylenedioxymethamphetamine (MDMA) in raw wastewater over 7 years (2011–17); (ii) address overall drug use by estimating the average number of combined doses consumed per day in each city; and (iii) compare these with existing prevalence and seizure data. Design Analysis of daily raw wastewater composite samples collected over 1 week per year from 2011 to 2017. Setting and Participants Catchment areas of 143 wastewater treatment plants in 120 cities in 37 countries. Measurements Parent substances (amphetamine, methamphetamine and MDMA) and the metabolites of cocaine (benzoylecgonine) and of Δ9‐tetrahydrocannabinol (11‐nor‐9‐carboxy‐Δ9‐tetrahydrocannabinol) were measured in wastewater using liquid chromatography–tandem mass spectrometry. Daily mass loads (mg/day) were normalized to catchment population (mg/1000 people/day) and converted to the number of combined doses consumed per day. Spatial differences were assessed world‐wide, and temporal trends were discerned at European level by comparing 2011–13 drug loads versus 2014–17 loads. Findings Benzoylecgonine was the stimulant metabolite detected at higher loads in southern and western Europe, and amphetamine, MDMA and methamphetamine in East and North–Central Europe. In other continents, methamphetamine showed the highest levels in the United States and Australia and benzoylecgonine in South America. During the reporting period, benzoylecgonine loads increased in general across Europe, amphetamine and methamphetamine levels fluctuated and MDMA underwent an intermittent upsurge. Conclusions The analysis of wastewater to quantify drug loads provides near real‐time drug use estimates that globally correspond to prevalence and seizure data., This study was supported by the following countries, institutions and projects Australia: Thyne Reid foundation; Canada: Natural Sciences and Engineering Research Council of Canada (NSERC); Iceland: The Icelandic Research Fund (Grant number 163049–051); Slovenia: Slovene Research Agency (funding Project L1–9191); Spain: MINECO/AEI projects (CTM2014–56628‐C3–2‐R, CTQ2015–65603‐P, CTM2016–81935‐REDT, CTM2017–84763‐C3–2‐R), Galician Council of Culture, Education and Universities (ED481D 2017/003); UK: Environmental Sustainability Knowledge Transfer Network, Engineering and Physical Sciences Research Council and Thermo Fisher Scientific (CASE industrial scholarship for K. Munro, Ref.: EP/J502029/1). European Monitoring Centre for Drugs and Drug Addiction (EMCDDA); EU International Training Network SEWPROF (Marie Curie‐FP7‐PEOPLE, grant number 317205); COST Action ES1307 supported by COST (European Cooperation in Science and Technology); WATCH (Wastewater Analysis of Traces of illicit drug‐related Chemicals for law enforcement and public Health DG migration and Home affairs ‐ HOME/2015/ISFP/PR/DRUG/0062). Sampling support and provision of catchment information Austria: Klemens Geiger and Michael Schlapp; Belgium: Jonathan Phariseau, Bart Coene, Luc Van Os, Peter Nys, Dieter Lemaire, Jean‐François Mougel, Patrick Vantroyen and Karel Claes; Croatia: Marin Ganjto; Czech Republic: Jiri Stara and Robert Hrich Brněnské; France: Véronique Bremont; Italy: Roberto Mazzini and Francesca Pizza (Milan), Francesco Avolio (Bologna), Fabrizio Moratto and Sergio Ghezzi (Gorizia), Rosanna Brienza and Simona Panariello (Potenza), Pier Paolo Abis and Antonia Attanasio (Bari), Antonella Cicala (Palermo); Norway: Pia Ryrfors; Portugal: João Goulão, José Martins, Pedro Alvaro and Fátima Paixão; Slovakia: Silvia Antalová and Jozef Tichy; Spain: Begoña Martínez López, Cristian Mesa, Santiago Querol Rodriguez, Fernando Llavador, Enrique Albors and Gloria Fayos; the Netherlands: Alex Veltman, Peter Theijssen, Peter van Dijk, Stefan Wijers, Mark Stevens, Ferry de Wilde. Analytical support Australia: Maulik Ghetia; Cyprus: Popi Karaolia; Greece: Nikoilaos Raikos; Spain: Ana Maria Botero‐Coy, Clara Boix, Alberto Celma, Jorge Pitarch, Inés Racamonde and Eddie Fonseca; Italy: Emma Gracia‐Lor, Nikolaos I. Rousis and Noelia Salgueiro‐Gonzalez. Data repository and data screening Eawag: Harald von Waldow; EMCDDA: Renate Hochwieser, Liesbeth Vandam, João Matias and Federica Mathis.

Electrospun Poly (methyl methacrylate) fibrous nonwovens containing diazo-dye Chicago Sky Blue (CSB) and methyl cellulose (Methocel A15 LV) were fabricated and explored for CSB release for therapeutic purposes. The role of Methocel was to accelerate CSB release and make it tunable in the 20 h to 11 days range. The spectrofluorometric analysis revealed that the release rate and the ultimate released amount were affected by the nonwoven thickness, the surrounding liquid medium (DI water or PBS), wettability of the fiber mat, and the Methocel concentration. In several experiments some intriguing and repeatable oscillations in the amount of the released CSB in the presence of Methocel were observed and accompanied by the appearance of a new fluorescence peak at the wavelength of 680 nm. The Raman spectroscopy was also used to elucidate the nature of such oscillations. A kinetic mechanism is also proposed to explain the oscillations and the appearance of a new fluorescence peak by CSB dimerization and formation of relatively stable CSB dimers.

We have investigated gas‐phase fragmentation reactions of protonated benzofuran neolignans (BNs) and dihydrobenzofuran neolignans (DBNs) by accurate‐mass electrospray ionization tandem and multiple‐stage (MSn) mass spectrometry combined with thermochemical data estimated by Computational Chemistry. Most of the protonated compounds fragment into product ions B ([M + H–MeOH]+), C ([B–MeOH]+), D ([C–CO]+), and E ([D–CO]+) upon collision‐induced dissociation (CID). However, we identified a series of diagnostic ions and associated them with specific structural features. In the case of compounds displaying an acetoxy group at C‐4, product ion C produces diagnostic ions K ([C–C2H2O]+), L ([K–CO]+), and P ([L–CO]+). Formation of product ions H ([D–H2O]+) and M ([H–CO]+) is associated with the hydroxyl group at C‐3 and C‐3′, whereas product ions N ([D–MeOH]+) and O ([N–MeOH]+) indicate a methoxyl group at the same positions. Finally, product ions F ([A–C2H2O]+), Q ([A–C3H6O2]+), I ([A–C6H6O]+), and J ([I–MeOH]+) for DBNs and product ion G ([B–C2H2O]+) for BNs diagnose a saturated bond between C‐7′ and C‐8′. We used these structure‐fragmentation relationships in combination with deuterium exchange experiments, MSn data, and Computational Chemistry to elucidate the gas‐phase fragmentation pathways of these compounds. These results could help to elucidate DBN and BN metabolites in in vivo and in vitro studies on the basis of electrospray ionization ESI‐CID‐MS/MS data only.

Made available in DSpace on 2019-10-04T12:36:48Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-03-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Bemisia tabaci (Gennadius) biotype B (Hemiptera: Aleyrodidae) has developed resistance to numerous conventional insecticides, which has led us to investigate the toxicity of ten dihydrobenzofuran- (DBN) and benzofuran-type (BN) neolignans structurally related to conocarpan against second instar B. tabaci nymphs. At concentrations higher than 5mg/L, most of the tested compounds killed 100% of B. tabaci biotype B nymphs 6days after spraying. The contact toxicity of compounds 2 ((+/-)-trans-dehydrodiferulate dimethyl ester), 3 ((+/-)-4-O-methyl-trans-dehydrodiferulate dimethyl ester), 5 ((+/-)-4-O-acetyl-trans-dehydrodiferulate dimethyl ester), 6 ((+/-)-7,8-dihydro-trans-dehydrodicoumarate dimethyl ester), 8 ((+/-)-4-O-methyl-7,8-dihydro-trans-dehydrodiferulate dimethyl ester), and 10 ((+/-)-7,8-dihydro-7,8-dehydro-trans-dehydrodicoumarate dimethyl ester) was higher than the contact toxicity of pyriproxyfen at a concentration of 75mg/L, which was used as positive control. Repellent (compounds 2 and 7 ((+/-)-7,8-dihydro-trans-dehydrodiferulate dimethyl ester) and oviposition deterrent (compounds 2, 3, and 7) effects were observed for adult whiteflies exposed to leaves sprayed with DBNs for 24 and 48h, respectively. These results suggest that DBNs have potential application in the development of effective pest management compounds. Univ Estadual Paulista, Fac Ciencias Agron Botucatu, Dept Protecao Vegetal, Botucatu, SP, Brazil Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Quim, Ribeirao Preto, SP, Brazil Univ Estadual Paulista, Fac Ciencias Agron Botucatu, Dept Protecao Vegetal, Botucatu, SP, Brazil FAPESP: 2013/20094-0 FAPESP: 2016/16957-0

Optimisation of the antioxidant activity of asparagus root extract (ARE) and inosine from New Zealand and Chinese asparagus root cultivars was carried out using a response surface methodology (RSM) using Box-Behnken design (BBD). The determination of inosine was carried out using HPLC under optimal extraction conditions. The independent parameters variables combination (extraction temperature 51 °C, extraction time 73.02 min, ethanol 75.23% and solid: liquid ratio 1:50) produced maximum total flavonoids content (TFC) (9.2–17.1 mg RE/g dry root), total phenolic content (TPC) (14.7–35.2 mg GAE/g dry root) and total saponin content (TSC) (9.2–17.1 mg RE/g dry root). Extraction at temperature 50 °C for 78.5 min, using 70% ethanol at solid: liquid ratio of 1:40 for maximum 2,2-diphenyl-1-picrylhydracyl (DPPH) (38.9–78.1%), 2,2-azinobis(3-ethylbenzo-thiazoline-6-sulfonate) (ABTS) (36.6–61.2%), ferric reducing antioxidant power assay (FRAP) (0.54–1.69 μmol/g), β-carotene bleaching assay (51.2–76.0%) and superoxide anion radical (O2−) scavenging capacity (42.5–70.2%). For methanol, extraction conditions viz. extraction temperature at 51 °C for 75 min, using 75% methanol at solid: liquid ratio of 1:50 resulted in maximum TFC (12.0–13.4 mg RE/g dry root), TPC (25.1–26.2 mg GAE/g dry root) and TSC (5.9–6.4 mg SE/g dry root). Extraction temperature at 50 °C for 76.5 min using 80% methanol at solid: liquid ratio of 1:50 produced maximum%DPPHsc (55.8–69.9%), %ABTSsc (43.0–52.0%), FRAP (0.54–0.59 μmol/g dry root), %βsc (49.2%–71.2%) and%O2−sc (34.4–41.6%). The content of inosine from ARC ranged from 1.3 to 6.0 mg/g with ethanol and from 0.9 to 4.1 mg/g with methanol extraction.

The imbalance of hydrophilicity and lipophilicity along with a large molecular size (due to a unique chemical structure) of natural compounds or plant actives poses a significant challenge for their absorption through a biological membrane and thus, alters the therapeutic efficacy. Therefore, it is desirable to have a novel approach for such formulation in order to improve the solubility and bioavailability of these phytoconstituents as a phospholipid complexation. Herbal drugs are precisely, embedded and bound by phospholipids to form vesicular structures which are amphoteric in nature. Thus, the phytolipid complex technology is unique, in the respect that it has a higher stability profile owing to its amphoteric nature or owing to its solubility in aqueous as well as oil media. It also exhibits a greater absorption and bioavailability, as the drug molecules are embedded in the pockets of the phytosomal assembly, therefore, with more drug loading capability, protection from the gastric environment, and subsequently inactivation in gastro-intestinal tract (GIT). Phytolipid complexes have a great potential in the field of medicine, pharmaceuticals and cosmetics due to improved pharmacokinetics and pharmacological attributes. The present review explores the various aspects of phytolipid complexes concerning the phospholipids, vesicles, choice of ingredients, phytolipid complexation, advantages, preparation methods and their applications.

In this study, the effect of antimicrobial photodynamic therapy (aPDT) and aPDT combined with antibiotics to inactivate Staphylococcus aureus in vitro and ex vivo was compared. The tetracationic porphyrin 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin tetra-iodide (Tetra-Py+-Me) was used to inactivate S. aureus in phosphate buffer solution (PBS) (in vitro) and in pork skin artificially contaminated with S. aureus (ex vivo). The results showed an efficient reduction of 8 log in PBS, after 180 min of irradiation under white light at 4.0 mW cm−2 with Tetra-Py+-Me at 5.0 μM. When aPDT was repeated in the presence of antibiotics, an increased effect was observed with ampicillin at 0.5 and 1.0 μg mL−1 (MIC 0.25 μg mL−1) – the full inactivation (8 log) occurred faster, respectively, after 60 and 30 min of irradiation. In ex vivo, a reduction of ∼4 log of S. aureus was observed after 180 min with 50 μM of Tetra-Py+-Me at 150 mW cm−2, but this efficiency increased significantly with the application of three successive light cycles (reduction to the detection limit ∼6 log). The photoinactivation efficiency observed in ex vivo was also significantly improved when the experiments with 50 μM of Tetra-Py+-Me were repeated in the presence of 5.0 μg mL−1 of ampicillin (inactivation of ∼5.6 log). The results showed that aPDT is an effective approach to control S. aureus infection in skin, inactivating the bacterium to the detection limit after three successive cycles of treatment or after one cycle by using the combination aPDT and ampicillin.

Background: Platelet-rich fibrin (PRF) has gained popularity in craniofacial surgery, as it provides an excellent reservoir of autologous growth factors (GFs) that are essential for bone regeneration. However, the low elastic modulus, short-term clinical application, poor storage potential and limitations in emergency therapy use restrict its more widespread clinical application. This study fabricates lyophilised PRF (Ly-PRF), evaluates its physical and biological properties, and explores its application for craniofacial tissue engineering purposes. Material and methods: A lyophilisation method was applied, and the outcome was evaluated and compared with traditionally prepared PRF. We investigated how lyophilisation affected PRF’s physical characteristics and biological properties by determining: (1) the physical and morphological architecture of Ly-PRF using SEM, and (2) the kinetic release of PDGF-AB using ELISA. Results: Ly-PRF exhibited a dense and homogeneous interconnected 3D fibrin network. Moreover, clusters of morphologically consistent cells of platelets and leukocytes were apparent within Ly-PRF, along with evidence of PDGF-AB release in accordance with previously reports. Conclusions: The protocol established in this study for Ly-PRF preparation demonstrated versatility, and provides a biomaterial with growth factor release for potential use as a craniofacial bioscaffold.

Made available in DSpace on 2018-12-11T16:49:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-01-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) The development of polymeric fibers incorporated with nickel (Ni) nanoparticles (NPs) has gained broad interest due to its applications, mainly for impurities removal from oil with the aid of magnetic field. In the present study, poly(vinylidene fluoride) (PVDF) fibers containing Ni NPs were produced by solution blow spinning (SBS) technique. Scanning electron microscope (SEM) measurements showed fibers with an average diameter of 564 nm, randomly dispersed without a preferred orientation. X-ray spectrum shows peaks related to Ni showing that Ni NPs were incorporated into the fibers. The magnetic analysis of the nanocomposite shows the hysteresis loops typical of ferromagnetic behavior and ZFC–FC curves revealed the presence of superparamagnetic behaviour and an average blocking temperature of 165 K. The results achieved in this work showed that is possible to produce fibrous material, using SBS technique, with unusual magnetic properties that may be applicable in various fields, including different areas of technological industry. Faculdade de Engenharia Universidade Estadual Paulista (UNESP), Câmpus de Ilha Solteira Grupo de Supercondutividade e Magnetismo Departamento de Física Universidade Federal de São Carlos Faculdade de Engenharia Universidade Estadual Paulista (UNESP), Câmpus de Ilha Solteira FAPESP: 09/54082-2 FAPESP: 2016/11459-2

The aim of present investigation was to characterize carboxymethyl tamarind gum (CMTG) based interpenetrating networks (IPNs) of aceclofenac for site specific sustained delivery. The drug loaded IPNs were prepared by using chitosan and CMTG as polymers and gluteraldehyde as crosslinking agent. The IPNs were characterized by Attenuated total reflectance- Fourier transform infrared (ATR-FTIR) spectroscopy, thermal analysis, X-ray powder diffraction and solid state 13C-nuclear magnetic resonance spectroscopy. The prepared IPNs were evaluated for the drug entrapment efficiency and equilibrium swelling. The drug release from IPNs was studied in 0.1NHCl for 2h followed by phosphate buffer pH 6.8 for further 10h and compared with commercial tablet. The results of ATR-FTIR and thermal analysis for blank IPNs indicated intercalation of polymeric chains of crosslinked CMTG and chitosan. The results of solid state characterization revealed that the aceclofenac is compatible with IPNs. Entrapment efficiency of IPNs was found to be increased with increase in crosslinker concentration as well as amount of CMTG. The equilibrium swelling study indicated pH dependent swelling of IPNs. The drug release by IPNs showed sustained release of aceclofenac upto 12h while commercial formulation showed fast release within 8h. From the results, it can be concluded that the IPNs of CMTG and chitosan has potential in development of site specific sustained drug delivery.

A direct synthesis of several 1,2-disubstituted 4-, 5-, 6-, and 7-azaindoles from available amino-o-halopyridines is described. This procedure involves a palladium-catalyzed N-arylation followed by a Sonogashira reaction and subsequent cyclization in a one-pot manner, exhibiting a wide scope and compatibility with electron-withdrawing and electron-donating groups. The strategy represents an advancement in azaindole chemistry with a straightforward approach toward 1,2-disubstituted azaindoles, while avoiding complex N-arylations of hindered 2-substituted azaindoles and difficult purification steps of intermediates.

Bone tissue engineering has emerged as one of the most indispensable approaches to address bone trauma in the past few decades. This approach offers an efficient and a risk-free alternative to autografts and allografts by employing a combination of biomaterials and cells to promote bone regeneration. Hydroxyapatite (HA) is a ceramic biomaterial that mimics the mineral composition of bones and teeth in vertebrates. HA, commonly produced via several synthetic routes over the years has been found to exhibit good bioactivity, biocompatibility, and osteoconductivity under both in vitro and in vivo conditions. However, the brittle nature of HA restricts its usage for load bearing applications. To address this problem, HA has been used in combination with several polymers in the form of biocomposite implants to primarily improve its mechanical properties and also enhance the implants' overall performance by simultaneously exploiting the positive effects of both HA and the polymer involved in making the biocomposite. This review article summarizes the past and recent developments in the evolution of HA-polymer biocomposite implants as an "ideal" biomaterial scaffold for bone regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2046-2057, 2018.

Citric acid crosslinked β-cyclodextrin–carboxymethylcellulose (βCD-CMC) hydrogel films were prepared by esterification-crosslinking method for the controlled release of ketoconazole (model drug). The hydrogel films were evaluated for active βCD content, carboxyl content, swelling ratio, drug loading and release, and hemolytic activity. The structural characterization was carried out using solid state 13 C NMR, ATR-FTIR, TGA and DSC analysis. The βCD-CMC hydrogel films showed increase in active βCD content swelling ratio and drug loading with increase in the concentration of βCD in the feed. The βCD helped to minimize the burst effect and retarded the release of ketoconazole. The hydrogel films were found to be biocompatible and capable of controlling the release of ketoconazole for long duration.

Carbon–carbon and carbon–heteroatom coupling reactions are among the most important transformations in organic synthesis as they enable complex structures to be formed from readily available compounds under different routes and conditions. Several metal-catalyzed cross-coupling reactions have been developed creating many efficient methods accessible for the direct formation of new bonds between differently hybridized carbon atoms.During the last decade, much effort has been devoted towards improvement of the sustainability of these reactions, such as catalyst recovery and atom efficiency. Polyethylene glycol (PEG) can be used as a medium, as solid-liquid phase transfer catalyst, or even as a polymer support. PEG has been investigated in a wide variety of cross-coupling reactions either as an alternative solvent to the common organic solvents or as a support for catalyst, substrate, and ligand. In this review we will summarize the different roles of PEG in palladium- and copper-catalyzed cross-coupling reactions, with the focus on Heck, Suzuki–Miyaura, Sonogashira, Buchwald–Hartwig, Stille, Fukuyama, and homocoupling reactions. We will highlight the role of PEG, the preparation of PEGylated catalysts and substrates, and the importance for the reaction outcome and applicability.1 Introduction2 PEG in Heck Reactions3 PEG in Homocoupling Reactions4 PEG in Suzuki–Miyaura Reactions5 PEG in Sonogashira Reactions6 PEG in Buchwald–Hartwig Reactions7 PEG in Stille Reactions8 PEG in Fukuyama Reactions9 PEG in Miscellaneous Cross-Coupling Routes10 Conclusions

This study reports on the chemical composition and antimicrobial activity of the essential oil from Artemisia absinthium L. leaves AA EO collected in Brazil against a representative panel of cariogenic bacteria. The minimum inhibitory concentrations MICs were determined by the broth dilution method in 96-well microplates. AA EO was inactive against most of the investigated oral pathogens, but it displayed moderate activity against Streptococcus mutans MIC = 250 μg/mL and very promising activity against Streptococcus mitis MIC = 62.5 μg/mL. Gas chromatography GC FID and gas chromatography mass spectrometry GC-MS revealed that camphor 1, 19.0 %, E-caryophyllene 2, 9.3 %, eucalyptol 3, 6.8 %, germacrene D 6.7 %, and α-cadinol 6.5 % were the major chemical constituents of AA EO. However, when tested alone, compounds 1, 2, and 3 were inactive MIC > 1000 μg/mL against all the studied microorganisms.

Solution-processed metal oxides have been investigated as an alternative to vacuum-based oxides to implement low-cost, high-performance electronic devices on flexible transparent substrates. However, their electrical properties need to be enhanced to apply at industrial scale. Amorphous indium-gallium-zinc oxide (a-IGZO) is the most-used transparent semiconductor metal oxide as an active channel layer in thin-film transistors (TFTs), due to its superior electrical properties. The present work evaluates the influence of composition, thickness and ageing on the electrical properties of solution a-IGZO TFTs, using solution combustion synthesis method, with urea as fuel. After optimizing the semiconductor properties, low-voltage TFTs were obtained by implementing a back-surface passivated 3-layer In:Ga:Zn 3:1:1 with a solution-processed high-к dielectric, AlOx. The devices show saturation mobility of 3.2 cm2 V&minus, 1 s&minus, 1, IOn/IOff of 106, SS of 73 mV dec&minus, 1 and VOn of 0.18 V, thus demonstrating promising features for low-cost circuit applications.

The filamentous fungus Trametes versicolor is a rich source of laccase (Tvlac). Laccases catalyze reactions that convert substituted phenol substrates into diverse derivatives through aromatic oxidation. We investigated methyl p-coumarate, methyl ferulate, and methyl caffeate biotransformation by Trametes versicolor ATCC 200801. Despite substrate similarity, the biotransformation reactions varied widely. Only methyl p-coumarate was converted into three derivatives. We isolated and identified the chemical structures of such derivatives by NMR and IR analysis. Hydroxylation, methylation, and hydrolysis were the main reactions resulting from the studied biotransformation. We also analyzed the interactions between Tvlac (PDB ID: 1GYC) and the three phenolic substrates by molecular docking simulations. The substituents in the phenol ring influenced substrate conformation and orientation in the Tvlac site. The biotransformation reaction selectivity correlated with the different binding energies to the Tvlac site. Our results demonstrated that docking studies successfully predict the biotransformation of cinnamic acid analogs by T. versicolor.

The aim of the study was to evaluate the effectiveness of polyherbal formulation on cataract development in streptozotocin-nicotinamide-induced diabetic rats. Diabetes was induced by streptozotocin (65 mg/kg, ip) and nicotinamide (90 mg/kg, ip). The diabetic rats were orally treated with polyherbal formulation (therapeutic dose, 28.71 mg/kg and 2×therapeutic dose, 57.42 mg/kg) and metformin (150 mg/kg), for 12 weeks. Serum glucose levels, body weight, histopathology of pancreas were used to evaluate the antidiabetic activity while the histopathological study of eye and protein content in lens were used to evaluate the protective effect of polyherbal formulation on cataract development. The progression of cataract in rat lens was observed with a slit-lamp biomicroscope. A daily treatment of polyherbal formulation for 12 weeks resulted in significant (p

e13017 Background: Activation of the mammalian target of rapamycin intracellular signaling pathway is one of the mechanisms of endocrine resistance in breast cancer. The addition of everolimus to exemestane improves progression-free survival (PFS) in patients with hormone receptor positive (HR+) advanced breast cancer (ABC) previously treated with nonsteroidal aromatase inhibitors (NSAIs). The aim of this study was to assess the effectiveness and safety of everolimus plus exemestane in patients with HR+ ABC. Methods: We retrospectively evaluated patients with HR+, HER2 negative ABC treated with everolimus/exemestane that recurred or progressed during/after treatment with NSAIs in a portuguese comprehensive cancer center. Study endpoints were PFS, overall survival (OS), overall response rate and adverse events. Results: Between April 2014 and September 2020, 63 female patients were treated with everolimus/exemestane. Median age was 59 years (36-79), and all had performance status ECOG ≤2. Seventeen (27.0%) patients had bone metastasis alone, 39 (61.9%) had bone and visceral metastasis, 25 (39.7%) had metastasis in 3 or more sites and 87.3% had previous hormone-sensitive disease. Before everolimus/exemestane, 61 (96.8%) patients were being treated with palliative endocrine therapy (alone or in combination with CDK4/6 inhibitors) or chemotherapy (ChT) and 2 (3.2%) patients were under adjuvant endocrine therapy. Median follow-up time was 12.8 months (1.4-74.6), with 39 patients alive. Overall response rate was 14.3% (1 complete response and 8 partial responses) and 45 patients had stable disease. Median PFS was 5.6 months (CI95% 2.4-8.8) and median OS was 25.4 months (CI95% 10.3-40.5). Subgroup analysis regarding PFS was statistically significant for previous treatment with CDK4/6 inhibitors (p = 0.026) and for site of metastasis (p = 0.025). In the subgroup of patients that previously underwent palliative ChT, median PFS was 4.0 months (CI95% 0.2-9.6) and median OS was 18.6 months (CI95% 8.2-29.0). For patients that did not receive previous palliative ChT, median PFS was 5.8 months (CI95% 3.8-7.8) and median OS was 43.5 months (CI95% 2.0-85.0). Grade 3 and 4 adverse events occurred in 21 (33.3%) patients, and were: nausea, anorexia, rash, headache, haematologic toxicity, hepatic cytolysis, hyperglycaemia, pneumonitis, oral mucositis and acute kidney failure with need for haemodialysis. Fifty-five (87.3%) patients suspended everolimus, 34 (54.0%) due to disease progression and 21 (33.3%) due to toxicity. Conclusions: Our results confirm the effectiveness and safety of everolimus/exemestane in real-world setting and support its use mainly before palliative ChT. Everolimus/exemestane in HR+ ABC is feasible in the clinic, with toxicity manageable under close surveillance.

Reconstituted keratin-hydroxyapatite (K-HA) composites have shown potential as nonload-bearing bone graft substitute material. This in vivo study investigated the bone regeneration response of keratin plus 40% HA composite materials in comparison to collagen counterparts and an unfilled defect site. The implantation site was a noncritical size defect created in the long bones (tibia) of sheep, with observations made at 1, 2, 4, 6, 8, and 12 weeks postimplantation. Porous K-HA materials displayed an excellent biocompatibility similar to collagen counterparts; however, the rate of bone regeneration at K-HA implantation sites was markedly slower than that of the collagen or unfilled defect sites. While collagen materials were undetectable by 4 weeks implantation, K-HA composite remnants were present at 12 weeks. However, there is evidence that K-HA implants participated in the natural remodelling process of bone, with bone regeneration occurring via a creeping substitution mechanism. Observations imply that the rate of bone ingrowth into the K-HA defect site was matched with the rate of K-HA resorption. These results suggest that K-HA materials may offer significant benefits as nonload-bearing bone graft substitutes where it is desirable that the degradation of the scaffolding material be well matched with the rate of bone regeneration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2034-2044, 2017.

A practical palladium-catalyzed cascade C-N cross-coupling/Heck reaction of alkenyl bromides with amino-o-bromopyridines is described for a straightforward synthesis of substituted 4-, 5-, 6-, and 7-azaindoles using a Pd2(dba)3/XPhos/t-BuONa system. This procedure consists of the first cascade C-N cross-coupling/Heck approach toward all four azaindole isomers from available aminopyridines. The scope of the reaction was investigated and several alkenyl bromides were used, allowing access to different substituted azaindoles. This protocol was further explored for N-substituted amino-o-bromopyridines.