Search

Schistosoma mansoni, an intravascular parasitic worm and the causative agent of schistosomiasis, relies on its tegument (outer layer) for survival and host interaction. This study explored the morphology and mechanical properties of S. mansoni tegument using Atomic Force Microscopy (AFM). Notably, we employed the PeakForce Quantitative Nanomechanical Mapping (PF-QNM) mode in air, enabling simultaneous acquisition of 3D topography and mechanical property contrasts (adhesion, elastic modulus). Additionally, nanoindentation (AFM contact mode) was performed on female worm tegument for elastic modulus measurement. Both techniques revealed an elastic modulus range of fractions or units of GPa for the tegument. Interestingly, mechanical property maps, particularly adhesion contrast, displayed a recurring pattern of light and dark bands. We also measured the depth of annular furrows on the female tegument, finding an average of 128 ± 10 nm. These findings establish AFM, particularly PF-QNM, as a valuable tool to characterize S. mansoni tegument properties, offering insights for future investigations into parasite biology and its response to immunological or pharmacological challenges., (© 2024. The Author(s).)

Background: Schistosomiasis, caused by the parasitic blood fluke Schistosoma mansoni, is a significant global health concern, particularly in tropical and subtropical regions. The available chemotherapeutic drug is restricted to praziquantel with present problems related to efficacy, toxicity and resistance, justifying the search for new drugs. Different natural products, including γ-lactones, have demonstrated anthelmintic activity. Thus, in this study, new γ-lactones from Porcelia ponderosa were investigated for their anti-S. mansoni effects in vitro and in vivo., Purpose: To evaluate the therapeutical potential against S. mansoni of the mixture of γ-lactones 1 + 2 obtained from Porcelia ponderosa seeds., Study Design and Methods: The precipitate formed during the concentration of CH 2 Cl 2 extract from seeds of P. ponderosa showed to be composed by a mixture of the new γ-lactones 1 + 2 (in a ratio 77:23) which were chemically characterized using NMR and ESI-HRMS. This mixture was evaluated in vitro and in vivo against S. mansoni, using a murine model of schistosomiasis. Additionally, toxicity of the mixture of 1 + 2 (77:23) was determined using mammalian cell lines (in vitro) or the model organism Caenorhabditis elegans (in vivo)., Results: Seeds of P. ponderosa afforded a mixture of two unreported γ-lactones, 3‑hydroxy-4-methylene-2-(tetracosa-17'Z,23'-diene-13',15'-diynyl)‑but-2-enolide (1) and 3‑hydroxy-4-methylene-2-(tetracos-17'Z-ene-13',15'-diynyl)‑but-2-enolide (2). Initially, the antischistosomal activity of the mixture of 1 + 2 (77:23) was investigated in vitro, and obtained results demonstrate reduced activity against Schistosoma mansoni worms (EC 50 of 83.3 μg/ml) in comparison to positive control praziquantel (EC 50 of 1.5 μg/ml). However, when tested in vivo using oral administration at 400 mg kg -1 , the standard dose used in the murine model of schistosomiasis, the mixture of 1 + 2 (77:23) revealed expressive reductions in both worm burden (65.7 %) and egg production (97.2 %), similar of those observed to praziquantel (89.7 % and 91.5 %, respectively). On the other hand, when treated using 200 and 100 mg kg -1 , reductions in worm burden (25.7 and 12.4 %) and egg production (33.6 and 13.3 %) were also observed. Importantly, the mixture of 1 + 2 (77:23) exhibited no toxicity using mammalian cell lines (in vitro) or C. elegans (in vivo)., Conclusion: Considering the promising in vivo activity of γ-lactones from P. ponderosa, the mixture of 1 + 2 (77:23) can be considered as promising candidate for the development of novel antischistosomal therapeutics, underscoring the importance of biodiversity exploration in the search for effective treatments against neglected tropical diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

The liver plays a crucial role in lipid metabolism and metabolic homeostasis. Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common chronic liver disease worldwide and currently has no specific treatments. Lifestyle modifications such as weight loss, exercise, and dietary changes are recommended to reduce the risk factors associated with the disease. Oxidized cholesterol products, some phospholipids and diacylglycerols can activate inflammatory pathways and contribute to the progression to Non-Alcoholic Steatohepatitis. Monitoring the whole plasma and liver lipidome may provide insights into the onset, development, and prevention of inflammatory-related diseases. As Lipid Droplets (LDs) represent augmented lipid reservoirs in NAFLD, new developments are being made on different therapies focused on LD associated proteins modulation (seipin, PLIN-2), as well as LD lipophagy mechanisms. The information covered in this publication provides an overview of the available research on lipid biomarkers linked to NAFLD and can be used to guide the development of future pharmacological therapies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Melanoma is originated from the malignant transformation of the melanocytes and is characterized by a high rate of invasion, the more serious stage compromising deeper layers of the skin and eventually leading to the metastasis. A high mortality due to melanoma lesion persists because most of melanoma lesions are detected in advanced stages, which decreases the chances of survival. The identification of the principal mechanics implicated in the development and progression of melanoma is essential to devise new early diagnosis strategies. Cell mechanics is related with a lot of cellular functions and processes, for instance motility, differentiation, migration and invasion. In particular, the elastic modulus (Young's modulus) is a very explored parameter to describe the cell mechanical properties; most cancer cells reported in the literature smaller elasticity modulus. In this work, we show that the elastic modulus of melanoma cells lacking galectin-3 is significantly lower than those of melanoma cells expressing galectin-3. More interestingly, the gradient of elastic modulus in cells from the nuclear region towards the cell periphery is more pronounced in shGal3 cells. RESEARCH HIGHLIGHTS: AFM imaging and force spectroscopy were used to investigate the morphology and elasticity properties of healthy HaCaT cells and melanoma cells WM1366, with (shSCR) and without (shGal3) expression of galectin-3. It is shown the effect of galectin-3 protein on the elastic properties of cells: the cells without expression of galectin-3 presents lower elastic modulus. By the results, we suggest here that galectin-3 could be used as an effective biomarker of malignancy in both melanoma diagnostic and prognosis., (© 2023 Wiley Periodicals LLC.)

Saccharum officinarum L. exploitation and processing result in different byproducts, such as filter cake (FC). This study aimed to establish the most suitable experimental conditions to obtain lipophilic bioactive compounds from FC industrial residues, considering their high efficiency, cost-effectiveness, extraction yield, composition, and physicochemical properties. Results indicated that the most appropriate methodology consisted of the pretreatment of the FC sample with H 2 SO 4 , followed by ethanolic extraction (B6 method), avoiding energy-consumption FC drying steps and providing ethanol recovery (approx. 90%). The obtained B6 extract yield was 9.59 ± 0.27 g/100 g of FC dry weight, and this methodology proved to be more efficient in obtaining fatty alcohols (20.28 ± 1.48 g/kg extract) and phytosterols (31.56 ± 0.18 g/kg extract) while maintaining lower total monosaccharide concentration (26.19 ± 1.82 mg/g extract). Furthermore, the geographically related multivariate analysis in wax composition and antioxidant activity was evaluated by comparing B6 waxes from Guariba (G) and Univalem (U), both provided by Brazil and collected in June 2020. Overall, the wax composition is affected, but the antioxidant activity is uncompromised, which indicates that the optimized wax extraction method can be applied to FC., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Schistosomiasis is a parasitic disease that afflicts approximately 250 million people worldwide. There is an urgent demand for new antiparasitic agents because praziquantel, the only drug available for the treatment of schistosomiasis, is not universally effective and may derail current progress toward the WHO goal of eliminating this disease as a public health problem by 2030. Nifuroxazide (NFZ), an oral nitrofuran antibiotic, has recently been explored to be repurposed for parasitic diseases. Here, in vitro , in vivo , and in silico studies were conducted to evaluate the activity of NFZ on Schistosoma mansoni. The in vitro study showed significant antiparasitic activity, with 50% effective concentration (EC 50 ) and 90% effective concentration (EC 90 ) values of 8.2 to 10.8 and 13.7 to 19.3 μM, respectively. NFZ also affected worm pairing and egg production and induced severe damage to the tegument of schistosomes. In vivo , a single oral dose of NFZ (400 mg/kg of body weight) to mice harboring either prepatent or patent S. mansoni infection significantly reduced the total worm burden (~40%). In patent infection, NFZ achieved a high reduction in the number of eggs (~80%), but the drug caused a low reduction in the egg burden of animals with prepatent infection. Finally, results from in silico target fishing methods predicted that serine/threonine kinases could be one of the potential targets for NFZ in S. mansoni. Overall, the present study revealed that NFZ possesses antischistosomal properties, mainly in terms of egg burden reduction in animals with patent S. mansoni infection. IMPORTANCE The increasing recognition of the burden imposed by helminthiasis, associated with the limited therapeutic arsenal, has led to initiatives and strategies to research and develop new drugs for the treatment of schistosomiasis. One of these strategies is drug repurposing, which considers low-risk compounds with potentially reduced costs and shorter time for development. In this study, nifuroxazide (NFZ) was evaluated for its anti-Schistosoma mansoni potential through in vitro , in vivo , and in silico studies. In vitro , NFZ affected worm pairing and egg production and induced severe damage to the tegument of schistosomes. In vivo , a single oral dose of NFZ (400 mg/kg) to mice harboring either prepatent or patent S. mansoni infection significantly reduced the total worm burden and egg production. In silico investigations have identified serine/threonine kinases as a molecular target for NFZ. Collectively, these results implied that NFZ might be a potential therapeutic candidate for the treatment of schistosomiasis., Competing Interests: The authors declare no conflict of interest.

Lipid molecules, such as policosanol, ergosterol, sphingomyelin, omega 3 rich phosphatidylcholine, α-tocopherol, and sodium butyrate, have emerged as novel additions to the portfolio of bioactive lipids. In this state-of-the-art review, we discuss these lipids, and their activity against obesity and mental or neurological disorders, with a focus on their proposed cellular targets and the ways in which they produce their beneficial effects. Furthermore, this available information is compared with that provided by in silico Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) models in order to understand the usefulness of these tools for the discovery of new bioactive compounds. Accordingly, it was possible to highlight how these lipids interact with various cellular targets related to the molecule transportation and absorption (e.g., α-tocopherol transfer protein for α-Tocopherol, ATP-binding cassette ABC transporters or Apolipoprotein E for sphingomyelins and phospholipids) or other processes, such as the regulation of gene expression (involving Sterol Regulatory Element-Binding Proteins for ergosterol or Peroxisome Proliferator-Activated Receptors in the case of policosanol) and inflammation (the regulation of interleukins by sodium butyrate). When comparing the literature with in silico Quantitative Structure-Activity Relationship (QSAR) models, it was observed that although they are useful for selecting bioactive molecules when compared in batch, the information they provide does not coincide when assessed individually. Our review highlights the importance of considering a broad range of lipids as potential bioactives and the need for accurate prediction of ADMET parameters in the discovery of new biomolecules. The information presented here provides a useful resource for researchers interested in developing new strategies for the treatment of obesity and mental or neurological disorders.

Lipid metabolism pathways such as β -oxidation, lipolysis and, lipogenesis, are mainly associated with normal liver function. However, steatosis is a growing pathology caused by the accumulation of lipids in hepatic cells due to increased lipogenesis, dysregulated lipid metabolism, and/or reduced lipolysis. Accordingly, this investigation hypothesizes a selective in vitro accumulation of palmitic and linoleic fatty acids on hepatocytes. After assessing the metabolic inhibition, apoptotic effect, and reactive oxygen species (ROS) generation by linoleic (LA) and palmitic (PA) fatty acids, HepG2 cells were exposed to different ratios of LA and PA to study the lipid accumulation using the lipophilic dye Oil Red O. Lipidomic studies were also carried out after lipid isolation. Results revealed that LA was highly accumulated and induced ROS production when compared to PA. Lipid profile modifications were observed after LA:PA 1:1 ( v / v ) exposure, which led to a four-fold increase in triglycerides (TGs) (mainly in linoleic acid-containing species), as well as a increase in cholesterol and polyunsaturated fatty acids (PUFA) content when compared to the control cells. The present work highlights the importance of balancing both PA and LA fatty acids concentrations in HepG2 cells to maintain normal levels of free fatty acids (FFAs), cholesterol, and TGs and to minimize some of the observed in vitro effects (i.e., apoptosis, ROS generation and lipid accumulation) caused by these fatty acids.

Schistosomiasis, a parasitic disease caused by the blood fluke of the genus Schistosoma, affects over 230 million people, especially in developing countries. Despite the significant economic and public health consequences, only one drug is currently available for treatment of schistosomiasis, praziquantel. Thus, there is an urgent demand for new anthelmintic agents. Based on our continuous studies involving the chemical prospection of floristic biodiversity aiming to discover new bioactive compounds, this work reports the in vitro antiparasitic activity against Schistosoma mansoni adult worms of neolignans threo-austrobailignan-6 and verrucosin, both isolated from Saururus cernuus L. (Saururaceae). These neolignans showed a significant in vitro schistosomicidal activity, with EC 50 values of 12.6-28.1 µM. Further analysis revealed a pronounced reduction in the number of S. mansoni eggs. Scanning electron microscopy analysis revealed morphological alterations when schistosomes were exposed to either threo-austrobailignan-6 or verrucosin. These relevant antischistosomal properties were accompanied by low cytotoxicity potential against the animal (Vero) and human (HaCaT) cell lines, resulting in a high selectivity index. Considering the promising chemical and biological properties of threo-austrobailignan-6 and verrucosin, this research should be of interest to those in the area of neglected diseases and in particular antischistosomal drug discovery., (© 2022. The Author(s).)

Sugarcane is primarily harvested to meet up to 80% of global sugar demand. Recently, lipids recovered from their biomass (straw and bagasse) have attracted much attention due to their possible utilisation in biofuel production but also by the presence of health-promoting compounds as phytosterols (i.e., improvement of cardiovascular function) or 1-octacosanol (i.e., anti-obesity). Although this fraction is commonly obtained through solid-liquid isolation, there is scarce information about how different solvents affect the composition of the extracts. This research work aimed to study whether, in sugarcane straw and bagasse samples, Soxtec extraction with widely used dichloromethane (DCM) would be suitable to recover most of the lipid classes when compared to other available solvents such as food grade ethanol (EtOH) or solvents without regulation restrictions for food and drug applications (i.e., acetone and ethyl acetate). The obtained results allow concluding that sugarcane waxes from straw and bagasse are complex lipid mixtures of polar and non-polar compounds. According to the extraction yield, the best results were obtained with ethanol (5.12 ± 0.30% and 1.97 ± 0.31%) for both straw and bagasse, respectively. The extractant greatly influenced the lipid composition of the obtained product. Thus, DCM enriched the isolates in glycerolipids (mono-, di- and triglycerides), free fatty acids, fatty alcohols, fatty aldehydes, phytosterols and hydrocarbons. On the other hand, EtOH resulted in polar isolates rich in glycolipids. Therefore, depending on the application and objectives of future research studies, the solvent to recover such lipids needs to be carefully selected.

In this study, we compared visual pictorial size perception between healthy volunteers (CG) and an experimental group (EG) of people diagnosed with schizophrenia. We have been using paintings by Salvador Dalí and Rorschach plates to estimate visual pictorial size perception. In this transversal, ex post facto, and quasi-experimental study, we observed differences between EG and CG. Schizophrenic in-patients perceived sizes about 1.3-fold greater than healthy volunteers (p=0.006), implying that pictorial size perception is altered in some way in schizophrenia. Considering the present and previous results, this measurement of diameter size of first pictorial perception may be a useful estimate of some aspects of perceptual alterations that may be associated with psychotic symptoms in prodromal and acute schizophrenic episodes and other related mental states. Eventually, this may help in preventing people from evolving to acute episodes., (© 2021. The Author(s).)

Aim: To isolate licochalcone A (LicoA) from licorice, prepare LicoA-loaded solid lipid nanoparticles (L-SLNs) and evaluate the L-SLNs in vitro and in vivo against Schistosoma mansoni . Materials & methods: LicoA was obtained by chromatographic fractionation and encapsulated in SLNs by a modified high shear homogenization method. Results: L-SLNs showed high encapsulation efficiency, with satisfactory particle size, polydispersity index and Zeta potential. Transmission electron microscopy revealed that L-SLNs were rounded and homogenously distributed. Toxicity studies revealed that SLNs decreased the hemolytic and cytotoxic properties of LicoA. Treatment with L-SLNs showed in vivo efficacy against S. mansoni . Conclusion: L-SLNs are efficient in reducing worm burden and SLNs may be a promising delivery system for LicoA to treat S. mansoni infections.

The intravascular parasitic worm Schistosoma mansoni is a causative agent of schistosomiasis, a disease of great global public health significance. Praziquantel is the only drug available to treat schistosomiasis and there is an urgent demand for new anthelmintic agents. Adopting a phenotypic drug screening strategy, here, we evaluated the antiparasitic properties of 46 commercially available cardiovascular drugs against S. mansoni. From these screenings, we found that amiodarone, telmisartan, propafenone, methyldopa, and doxazosin affected the viability of schistosomes in vitro, with effective concentrations of 50% (EC 50 ) and 90% (EC 90 ) values ranging from 8 to 50 µM. These results were further supported by scanning electron microscopy analysis. Subsequently, the most effective drug (amiodarone) was further tested in a murine model of schistosomiasis for both early and chronic S. mansoni infections using a single oral dose of 400 mg/kg or 100 mg/kg daily for five consecutive days. Amiodarone had a low efficacy in chronic infection, with the worm and egg burden reduction ranging from 10 to 30%. In contrast, amiodarone caused a significant reduction in worm and egg burden in early infection (>50%). Comparatively, treatment with amiodarone is more effective in early infection than praziquantel, demonstrating the potential role of this cardiovascular drug as an antischistosomal agent.

The unstoppable growth of human population that occurs in parallel with all manufacturing activities leads to a relentless increase in the demand for resources, cultivation land, and energy. In response, currently, there is significant interest in developing strategies to optimize any available resources and their biowaste. While solutions initially focused on recovering biomolecules with applications in food, energy, or materials, the feasibility of synthetic biology in this field has been demonstrated in recent years. For instance, it is possible to genetically modify Saccharomyces cerevisiae to produce terpenes for commercial applications (i.e., against malaria or as biodiesel). But the production process, similar to any industrial activity, generates biowastes containing promising biomolecules (from fermentation) that if recovered may have applications in different areas. To test this hypothesis, in the present study, the lipid composition of by-products from the industrial production of β-farnesene by genetically modified Saccharomyces cerevisiae are studied to identify potentially bioactive compounds, their recovery, and finally, their stability and in vitro bioactivity. The assayed biowaste showed the presence of triterpenes, phytosterols, and 1-octacosanol which were recovered through molecular distillation into a single fraction. During the assayed stability test, compositional modifications were observed, mainly for the phytosterols and 1-octacosanol, probably due to oxidative reactions. However, such changes did not affect the in vitro bioactivity in macrophages, where it was found that the obtained fraction decreased the production of TNF-α and IL-6 in lipopolysaccharide (LPS)-induced inflammation.

Background: Praziquantel is the only drug available to treat schistosomiasis, and there is an urgent demand for new anthelmintic agents. Methodology & results: We conducted in-depth in vitro and in vivo  studies and report a target fishing investigation. In vitro , tamoxifen was active against adult and immature worms at low concentrations (<5 μM). Tamoxifen at a single dose (400 mg/kg) or once daily for five consecutive days (100 mg/kg/day) in mice harboring either adult (patent infection) or juvenile (prepatent infection) significantly reduced worm burden (30-70%) and egg production (70-90%). Target fishing studies revealed propionyl-CoA carboxylase as a potential target for tamoxifen in Schistosoma   mansoni and glucose uptake by S. mansoni was also significantly reduced. Conclusion: Our results provide news evidence of antiparasitic effect of tamoxifen and reveal propionyl-CoA carboxylase as a potential target.

Most of the global sugar and ethanol supply trade comes from the harvesting of Saccharum officinarum (i.e., sugarcane). Its industrial processing results in numerous by-products and waste streams, such as tops, straw, filter cake, molasses and bagasse. The recovery of lipids (i.e., octacosanol, phytosterols, long-chain aldehydes and triterpenoids) from these residues is an excellent starting point for the development of new products for various application fields, such as health and well-being, representing an important feature of the circular economy. By selecting green scalable extraction procedures, industry can reduce its environmental impact. Refluxed ethanol extraction methods have been demonstrated to meet these characteristics. On the other hand, effective non-solvent methodologies such as molecular distillation and supercritical CO 2 extraction can fractionate lipids based on high temperature and pressure application with similar yields. Sugarcane lipophilic extracts are usually analyzed through gas chromatography (GC) and liquid chromatography (LC) techniques. In many cases, the identification of such compounds involves the development of high-temperature GC-MS/FID techniques. On the other hand, for the identification and quantification of thermolabile lipids, LC-MS techniques are suitable for the separation and identification of major lipid classes. Generically, its composition includes terpenes, phytosterols, tocopherol, free fatty acids, fatty alcohols, wax esters, triglycerides, diglycerides and monoglycerides. These compounds are already known for their interesting application in various fields such as pharma and cosmetics due to their anti-hypercholesterolemic, anti-hyperglycemic, antioxidant and anti-inflammatory properties.

Ethnopharmacological Relevance: Propolis has been used in folk medicine for thousands of years and, in the past few decades, it has attracted renewed interest. Although propolis has been traditionally used in many communities worldwide against parasitic diseases, its effect against Schistosoma mansoni infection remains unclear., Aim of the Study: To demonstrate the effects of Brazilian red propolis on Schistosoma mansoni ex vivo and in an animal model of schistosomiasis., Materials and Methods: In vitro, we monitored phenotypic and tegumental changes as well as the effects of the crude extract of propolis on pairing and egg production. In a mouse infected with either immature (early infection) or adult (chronic infection) worms, propolis was administered by oral gavage and we studied the influence of this natural product on worm burden and egg production., Results: Propolis 25 μg/mL reduced motility and caused 100% mortality of adult parasites ex vivo. Further analysis revealed a pronounced reduction in oviposition after exposure to propolis at sub-lethal concentrations. In addition, scanning electron microscopy showed morphological alterations in the tegument of schistosomes. In the animal model, propolis markedly reduced worm burden and egg production in both early and chronic S. mansoni infection when compared to untreated control animals., Conclusions: The efficacy of Brazilian red propolis in both in vitro and in vivo studies suggests its potential anthelmintic properties against S. mansoni infection., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We present a novel patient-specific fluid-solid-growth framework to model the mechanobiological state of clinically detected intracranial aneurysms (IAs) and their evolution. The artery and IA sac are modeled as thick-walled, non-linear elastic fiber-reinforced composites. We represent the undulation distribution of collagen fibers: the adventitia of the healthy artery is modeled as a protective sheath whereas the aneurysm sac is modeled to bear load within physiological range of pressures. Initially, we assume the detected IA is stable and then consider two flow-related mechanisms to drive enlargement: (1) low wall shear stress; (2) dysfunctional endothelium which is associated with regions of high oscillatory flow. Localized collagen degradation and remodelling gives rise to formation of secondary blebs on the aneurysm dome. Restabilization of blebs is achieved by remodelling of the homeostatic collagen fiber stretch distribution. This integrative mechanobiological modelling workflow provides a step towards a personalized risk-assessment and treatment of clinically detected IAs.

Background: Schistosomiasis is a socioeconomically devastating parasitic infection afflicting hundreds of millions of people and animals worldwide. It is the most important helminth infection, and its treatment relies solely on the drug praziquantel. Oral H1-antihistamines are available worldwide, and these agents are among the most widely used of all medications in children and adults. Given the importance of the drug repositioning strategy, we evaluated the antischistosomal properties of the H1-antihistamine drugs commonly used in clinical practices., Methods: Twenty-one antihistamine drugs were initially screened against adult schistosomes ex vivo. Subsequently, we investigated the anthelmintic properties of these antihistamines in a murine model of schistosomiasis for both early and chronic S. mansoni infections at oral dosages of 400 mg/kg single dose or 100 mg/kg daily for five consecutive days. We also demonstrated and described the ability of three antihistamines to induce tegumental damage in schistosomes through the use of scanning electron microscopy., Results: From phenotypic screening, we found that desloratadine, rupatadine, promethazine, and cinnarizine kill adult S. mansoni in vitro at low concentrations (5-15 µM). These results were further supported by scanning electron microscopy analysis. In an animal model, rupatadine and cinnarizine revealed moderate worm burden reductions in mice harboring either early or chronic S. mansoni infection. Egg production, a key mechanism for both transmission and pathogenesis, was also markedly inhibited by rupatadine and cinnarizine, and a significant reduction in hepatomegaly and splenomegaly was recorded. Although less effective, desloratadine also revealed significant activity against the adult and juvenile parasites., Conclusions: Although the worm burden reductions achieved are all only moderate, comparatively, treatment with any of the three antihistamines is more effective in early infection than praziquantel. On the other hand, the clinical use of H1-antihistamines for the treatment of schistosomiasis is highly unlikely.

Schistosomiasis is one of the most important parasitic infections in terms of its negative effects on public health and economics. Since praziquantel is currently the only drug available to treat schistosomiasis, there is an urgent need to identify new anthelmintic agents. Piplartine, also known as piperlongumine, is a biologically active alkaloid/amide from peppers that can be detected in high amounts in the roots of Piper tuberculatum. Previously, it has been shown to have in vitro schistosomicidal effects. However, its anthelmintic activity in an animal host has not been reported. In the present work, in vivo antischistosomal properties of isolated piplartine were evaluated in a mouse model of schistosomiasis infected with either adult (patent infection) or juvenile (pre-patent infection) stages of Schistosoma mansoni. A single dose of piplartine (100, 200 or 400 mg/kg) or daily doses for five consecutive days (100 mg/kg/day) administered orally to mice infected with schistosomes resulted in a reduction in worm burden and egg production. Treatment with the highest piplartine dose (400 mg/kg) caused a significant reduction in a total worm burden of 60.4% (P < 0.001) in mice harbouring adult parasites. S. mansoni egg production, a process responsible for pathology in schistosomiasis, was also significantly inhibited by piplartine. Studies using scanning electron microscopy revealed substantial tegumental alterations in parasites recovered from mice. Since piplartine has well-characterized mechanisms of toxicity, is easily available, and is cost-effective, our results indicate that this bioactive molecule derived from medicinal plants could be a potential lead compound for novel antischistosomal agents., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In this work, we present some properties and use of a nanocomposite formed by gold nanoparticles (NPs) into poly(methyl methacrylate) (PMMA) and its application as substrates for surface-enhanced Raman spectroscopy (SERS). The nanocomposite was formed using low-energy (49 eV) ion implantation of gold in PMMA using a cathodic arc plasma gun. The gold NPs are formed spontaneously from the implanted ions and they remain isolated from each other by the polymer medium surrounding them, ensuring a spacing between the NPs of less than 10 nm (hot spot places). The NPs form below the surface, protected from the environment, guaranteeing the stability of the composite layer. Moreover, here, we present an interesting approach to concentrate analyte molecules closer to the metal surface using the swelling effect in PMMA. Using absorption of the analyte, the molecules stay in the gaps between NPs, which is a good solution for one of the biggest challenges in SERS, that is, to guide molecules to the hot spot places., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

The treatment and control of schistosomiasis, a neglected disease that affects more than 200 million people worldwide, rely on the use of a single drug, praziquantel. A vaccine has yet to be developed and since new drug design and development is a lengthy and costly process, drug repurposing is a promising strategy. In this study, the efficacy of promethazine, a first-generation antihistamine, was evaluated against Schistosoma mansoni ex vivo and in a murine model of schistosomiasis. In vitro assays demonstrated that promethazine affected parasite motility, viability, and it induced severe tegumental damage in schistosomes. The LC 50 of the drug was 5.84 μM. Similar to promethazine, schistosomes incubated with atropine, a classical anticholinergic drug, displayed reduced motor activity. In an animal model, promethazine treatment was introduced at an oral dose of 100 mg/kg for five successive days at different intervals from the time of infection, for the evaluation of the stage-specific susceptibility (pre-patent and patent infections). Various parasitological criteria indicated the in vivo antischistosomal effects of promethazine: there were significant reductions in worm burden, egg production, and hepato- and splenomegaly. The highest worm burden reduction was achieved with promethazine in patent infections (> 90%). Taken together, considering the importance of the repositioning of drugs in infectious diseases, especially those related to poverty, our data revealed the possibility of promethazine repositioning as an antischistosomal agent., (Copyright © 2019 American Society for Microbiology.)

Schistosomiasis is a parasitic flatworm disease that infects over 200 million people worldwide, especially in poor communities. Treatment and control of the disease rely on just one drug, praziquantel. Since funding for drug development for poverty-associated diseases is very limited, drug repurposing is a promising strategy. In this study, from a screening of 13 marketed diuretics, we identified that spironolactone, a potassium-sparing diuretic, had potent antischistosomal effects on Schistosoma mansoni in vitro and in vivo in a murine model of schistosomiasis. In vitro , spironolactone at low concentrations (<10 µM) is able to alter worm motor activity and the morphology of adult schistosomes, leading to parasitic death. In vivo , oral treatment with spironolactone at a single dose (400 mg/kg) or daily for five consecutive days (100 mg/kg/day) in mice harboring either patent or prepatent infections significantly reduced worm burden, egg production, and hepato- and splenomegaly ( P <  0.05 to P <  0.001). Taken together, with the safety profile of spironolactone, supported by its potential to affect schistosomes, these results indicate that spironolactone could be a potential treatment for schistosomiasis and make it promising for repurposing., (Copyright © 2019 American Society for Microbiology.)

In this study, we evaluated the in vitro and in vivo schistosomicidal activities of chalcones against Schistosoma mansoni worms. In vitro assays revealed that chalcones 1 and 3 were the most active compounds, without affecting significantly mammalian cells. Confocal laser scanning microscopy and scanning electron microscopy studies revealed reduction on the numbers of tubercles and morphological alterations in the tegument of S. mansoni worms after in vitro incubation with chalcones 1 and 3. In a mouse model of schistosomiasis, the oral treatment (400 mg/kg) with chalcone 1 or 3 significantly caused a total worm burden reduction in mice. Chalcone 1 showed significant inhibition of the S. mansoni ATP diphosphohydrolase activity, which was corroborated by molecular docking studies. The results suggested that chalcones could be explored as lead compounds with antischistosomal properties., (© 2018 Wiley-VHCA AG, Zurich, Switzerland.)

Oxazine derivatives, a class of heterocyclic compounds, exhibit a variety of biological properties, such as anticonvulsant and antitumor activities. In this study, we evaluated the effect of two cyclohexene-fused 1,3-oxazines (cis‑1-benzyl-N-phenyl-1,4,4a,5,8,8a-hexahydro-3,1-benzoxazin-2-imine (1) and trans‑N-phenyl-1,4,4a,5,8,8a-hexahydro-3,1-benzoxazin-2-imine (2)) in cultures of Bacillus cereus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, Serratia marcescens, Shigella flexneri and Staphylococcus aureus by the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC). Additionally, the ex vivo antiparasitic activity of oxazines was assessed against Schistosoma mansoni, a helminth that is one of the major agents of the disease schistosomiasis Also, oxazines were evaluated on three tumor cell lines, NCI-H292 (human lung carcinoma), MCF-7 (human breast adenocarcinoma) and HEp-2 (human cervix carcinoma), and two normal cell lines (Vero and red blood cells). Bioassays revealed that oxazine 2 is more effective against bacteria than oxazine 1, with the lowest MIC and MBC values of 3.91 and 32.5μg/mL, respectively. Similarly, compound 2 demonstrated higher antiparasitic activity than 1, and scanning electron microscopy analysis showed several morphological alterations in the tegument of worms in a concentration-dependent manner. In contrast, both oxazines exhibited low cytotoxic effects on cancer and normal cell lines. These results indicated that oxazines exerted direct effects on bacteria and parasite schistosomes. More importantly, since schistosomiasis control programs rely on one drug, praziquantel, oxazines may have the potential to become new antischistosomal agents., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Schistosomiasis is a major public health problem worldwide, especially in poor communities. Since praziquantel is currently the only drug available to treat schistosomiasis, there is an urgent need to identify new antischistosomal drugs. Nerolidol is a sesquiterpene present as an essential oil in several plants that has been approved by the FDA. This study evaluated the in vivo antischistosomal activity of nerolidol in a mouse model of schistosomiasis infected with either adult or juvenile stages of Schistosoma mansoni. A single dose of nerolidol (100, 200 or 400 mg/kg) administered orally to mice infected with adult schistosomes resulted in a reduction in worm burden and egg production. Treatment with the highest nerolidol dose (400 mg/kg) caused significant reduction in a total worm burden of 70.06% (P < 0.001). Additionally, the technique of quantitative and qualitative oograms showed that a single 400 mg/kg nerolidol dose achieved an immature egg reduction of 84.6% (P < 0.001). In faecal samples, the Kato-Katz method also revealed a reduction of 75.2% in eggs/g at a dose of 400 mg/kg (P < 0.001). Furthermore, scanning electron microscopy revealed that nerolidol-mediated worm killing was associated with tegumental damage. In contrast to activity against adult S. mansoni infection, oral treatment with nerolidol 400 mg/kg had low efficacy in mice harbouring juvenile schistosomes. Since nerolidol is already in use globally as a food additive and has a proven safety record, evaluation of this natural compound's potential for treatment of schistosomiasis could be entirely cost effective in the near future., (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Chinese Hamster Ovary (CHO) cell cultures were grown on surfaces lithographed with periodic 3D hexagonal microcavity array morphology. The range of microcavity size (inscribed circle diameter) was from 12 μm to 560 μm. CHO cells were grown also on flat surfaces. The characterization was performed with respect to cell growth density (number of nuclei per unit area) by fluorescence optical microscopy and evaluated by correlation function analysis. We found that optimum microcavity radius was 80 μm, concerning to the maximum cell growth density, being even greater than the growth density on a flat (unstructured) substrate of the same material. This finding can be important for optimization of biotechnological processes and devices., (Copyright © 2016. Published by Elsevier B.V.)

In this work, novel and nontoxic fluorinated ionic liquids (FILs) that are totally miscible in water and could be used in biological applications, where fluorocarbon compounds present a handicap because their aqueous solubility (water and biological fluids) is in most cases too low, have been investigated. The self-aggregation behavior of perfluorosulfonate-functionalized ionic liquids in aqueous solutions has been characterized using conductometric titration, isothermal titration calorimetry (ITC), surface tension measurements, dynamic light scattering (DLS), viscosity and density measurements, and transmission electron microscopy (TEM). Aggregation and interfacial parameters have been computed by conductimetry, calorimetry, and surface tension measurements in order to study various thermodynamic and surface properties that demonstrate that the aggregation process is entropy-driven and that the aggregation process is less spontaneous than the adsorption process. The novel perfluorosulfonate-functionalized ILs studied in this work show improved surface activity and aggregation behavior, forming distinct self-assembled structures.

We describe an approach to ion implantation in which the plasma and its electronics are held at ground potential and the ion beam is injected into a space held at high negative potential, allowing considerable savings both economically and technologically. We used an "inverted ion implanter" of this kind to carry out implantation of gold into alumina, with Au ion energy 40 keV and dose (3-9) × 10(16) cm(-2). Resistivity was measured in situ as a function of dose and compared with predictions of a model based on percolation theory, in which electron transport in the composite is explained by conduction through a random resistor network formed by Au nanoparticles. Excellent agreement is found between the experimental results and the theory.

Whereas energetic ion beams are conventionally produced by extracting ions (say, positive ions) from a plasma that is held at high (positive) potential, with ion energy determined by the potential drop through which the ions fall in the beam formation electrode system, in the device described here the plasma and its electronics are held at ground potential and the ion beam is formed and injected energetically into a space maintained at high (negative) potential. We refer to this configuration as an "inverted ion source." This approach allows considerable savings both technologically and economically, rendering feasible some ion beam applications, in particular small-scale ion implantation, that might otherwise not be possible for many researchers and laboratories. We have developed a device of this kind utilizing a metal vapor vacuum arc plasma source, and explored its operation and beam characteristics over a range of parameter variation. The downstream beam current has been measured as a function of extraction voltage (5-35 kV), arc current (50-230 A), metal ion species (Ti, Nb, Au), and extractor grid spacing and beamlet aperture size (3, 4, and 5 mm). The downstream ion beam current as measured by a magnetically-suppressed Faraday cup was up to as high as 600 mA, and with parametric variation quite similar to that found for the more conventional metal vapor vacuum arc ion source.

We have explored the effects of atmospheric environment on Kelvin force microscopy (KFM) measurements of potential difference between different regions of test polycrystalline diamond surfaces. The diamond films were deposited by microwave plasma-assisted chemical vapor deposition, which naturally produces hydrogen terminations on the surface of the films formed. Selected regions were patterned by electron-beam lithography and chemical terminations of oxygen or fluorine were created by exposure to an oxygen or fluorine plasma source. For KFM imaging, the samples were mounted in a hood with a constant flow of helium gas. Successive images were taken over a 5-h period showing the effect of the environment on KFM imaging. We conclude that the helium flow removes water molecules adsorbed on the surface of the samples, resulting in differences in surface potential between adjacent regions. The degree of water removal is different for surfaces with different terminations. The results highlight the importance of taking into account the atmospheric environment when carrying out KFM analysis., (Copyright © 2012 Wiley Periodicals, Inc.)

This manuscript reports on the fabrication of plasmonic substrates using cathodic arc plasma ion implantation, in addition to their performance as SERS substrates. The technique allows for the incorporation of a wide layer of metallic nanoparticles into a polymer matrix, such as PMMA. The ability to pattern different structures using the PMMA matrix is one of the main advantages of the fabrication method. This opens up new possibilities for obtaining tailored substrates with enhanced performance for SERS and other surface-enhanced spectroscopies, as well as for exploring the basic physics of patterned metal nanostructures. The architecture of the SERS-active substrate was varied using three adsorption strategies for incorporating a laser dye (rhodamine): alongside the nanoparticles into the polymer matrix, during the polymer cure and within nanoholes lithographed on the polymer. As a proof-of-concept, we obtained the SERS spectra of rhodamine for the three types of substrates. The hypothesis of incorporation of rhodamine molecules into the polymer matrix during the cathodic arc plasma ion implantation was supported by FDTD (Finite-Difference Time-Domain) simulations. In the case of arrays of nanoholes, rhodamine molecules could be adsorbed directly on the gold surface, then yielding a well-resolved SERS spectrum for a small amount of analyte owing to the short-range interactions and the large longitudinal field component inside the nanoholes. The results shown here demonstrate that the approach based on ion implantation can be adapted to produce reproducible tailored substrates for SERS and other surface-enhanced spectroscopies.

Objective: To report the clinical progress of patients with Hodgkin's lymphoma treated with autologous transplantation after failure or relapse of first-line treatment with chemotherapy and/or radiation therapy., Methods: The results of a retrospective analysis of 31 patients submitted to autologous transplantation as second-line treatment, between April 2000 and December 2008, were analyzed. Fourteen men and seventeen women, with a median age of 27 years, were submitted to autologous transplantation for relapsed (n = 21) or refractory (n = 10) Hodgkin's lymphoma., Results: Mortality related to treatment in the first 100 days after transplant was 3.2%. With a mean follow-up period of 18 months (range: 1 to 88 months), the probability of global survival and progression-free survival in 18 months was 84 and 80%, respectively. The probability of global survival and progression-free survival at 18 months for patients with chemosensitive relapses (n = 21) was 95 and 90%, respectively, versus 60 and 45% for patients with relapses resistant to chemotherapy (n = 10) (p = 0.001 for global survival; p = 0.003 for progression-free survival). In the multivariate analysis, absence of disease or pretransplant disease < 5 cm were favorable factors for global survival (p= 0.02; RR: 0.072; 95%CI: 0.01-0.85) and progression-free survival (p= 0.01; RR: 0.040; 95%CI: 0.007-0.78)., Conclusion: Autologous transplantation of stem-cells is a therapeutic option for Hodgkin's lymphoma patients after the first relapse. Promising results were observed in patients with a low tumor burden at transplant.

We describe the design and implementation of a high voltage pulse power supply (pulser) that supports the operation of a repetitively pulsed filtered vacuum arc plasma deposition facility in plasma immersion ion implantation and deposition (Mepiiid) mode. Negative pulses (micropulses) of up to 20 kV in magnitude and 20 A peak current are provided in gated pulse packets (macropulses) over a broad range of possible pulse width and duty cycle. Application of the system consisting of filtered vacuum arc and high voltage pulser is demonstrated by forming diamond-like carbon (DLC) thin films with and without substrate bias provided by the pulser. Significantly enhanced film∕substrate adhesion is observed when the pulser is used to induce interface mixing between the DLC film and the underlying Si substrate.

We describe a small hollow-cathode plasma source suitable for small-scale materials synthesis and modification application. The supporting electrical system is minimal. The gaseous plasma source delivers a plasma ion current of up to about 1 mA. Here we outline the source construction and operation, and present some of its basic performance characteristics.

We describe a nanolithography process for a polymethylmethacrylate (PMMA) surface using scanning contact atomic force microscopy. Parallel furrows were scribed with a pyramidal silicon tip using the same scan mechanism as used to image samples. The PMMA was first electron beam irradiated using a scanning electron microscope and developed. The topography formed is reproducible and predictable. Material from the region where the tip scribes is moved to nearby regions, and aligned, elongated PMMA fragments are seen to decorate the valleys between furrows.