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The experiment was conducted to determine α-amylase activity and the effect of seven plant species extracts including Punica granatum L. (Punicaceae), Rheum officinale B. (Polygonaceae), Rhus coriaria L. (Anacardiaceae), Artemisia sieberi B. ( Compositae), Peganum harmala L. (Nitrariaceae) , Datura stramonium L. (Solanaceae) and Thymus vulgaris L. (Lamiaceae) on α-amylase activity of four stored insect pests including Callosobruchus maculatus F. (Coleoptera: Bruchidae), Rhyzopertha dominica F. (Coleoptera: Bostrichidae), Sitophilus granarius L. (Coleoptera: Curculionidae), and Trogoderma granarium E. (Coleoptera : Dermestidae). Also, gut pH and optimum temperature for α-amylase activity of these insects were determined. It was found that α - amylases midgut pH of all four insect species was acidic and optimum temperature was between 30 and 40 °C. Beyond these temperatures, the α-amylases activities sharply decreased. Plant extracts caused inhibitory activity on insect α-amylases varying from nearly 4% to 95% inhibition. D. stramonium and R. officinali extracts had the highest amylase inhibitory activity among the tested extracts, while methanolic extracts of P. harmala, and T. vulgaris (except for S. granaries α-amylase) showed the lowest inhibitory activity. Gel assays revealed that more than one isoform of α -amylase detected in midgut crude extracts of the four insect pests examined could be inhibited by the plant extracts. [ABSTRACT FROM AUTHOR]

The experiment was conducted to determine α-amylase activity and the effect of seven plant species extracts including Punica granatum L. (Punicaceae), Rheum officinale B. (Polygonaceae), Rhus coriaria L. (Anacardiaceae), Artemisia sieberi B. ( Compositae), Peganum harmala L. (Nitrariaceae) , Datura stramonium L. (Solanaceae) and Thymus vulgaris L. (Lamiaceae) on α-amylase activity of four stored insect pests including Callosobruchus maculatus F. (Coleoptera: Bruchidae), Rhyzopertha dominica F. (Coleoptera: Bostrichidae), Sitophilus granarius L. (Coleoptera: Curculionidae), and Trogoderma granarium E. (Coleoptera : Dermestidae). Also, gut pH and optimum temperature for α-amylase activity of these insects were determined. It was found that α - amylases midgut pH of all four insect species was acidic and optimum temperature was between 30 and 40 °C. Beyond these temperatures, the α-amylases activities sharply decreased. Plant extracts caused inhibitory activity on insect α-amylases varying from nearly 4% to 95% inhibition. D. stramonium and R. officinali extracts had the highest amylase inhibitory activity among the tested extracts, while methanolic extracts of P. harmala, and T. vulgaris (except for S. granaries α-amylase) showed the lowest inhibitory activity. Gel assays revealed that more than one isoform of α -amylase detected in midgut crude extracts of the four insect pests examined could be inhibited by the plant extracts. [ABSTRACT FROM AUTHOR]

This study was an attempt to prepare copper nanoparticles and to determine their catalytic activity employing walnut shell (WS) residue as a green support and a reusable material. The nanocatalyst was characterized though inductively coupled plasma optical emission spectrometry (ICP-OES), N2-sorption analysis, X-ray powder diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS), and transmission electron microscopy (TEM). The catalytic performance of CuNPs@WS was then studied in the preparation of propargylamines via a three-component reaction. The catalyst could be recovered and reused without a significant decrease in its activity over eight reaction cycles. The simple methodology described herein is an economic, ecofriendly and practical method accompanied by higher yields.

This study aimed to evaluate the potential of zinc oxide nanoparticles (ZnO NPs) in the biofortification of lentil seedlings and subsequently improve the Zn status in rats. In the first phase of the study, the effects of various ZnO NPs concentrations (0, 10, 20, 40, 80, and 160 ppm) on the lentil growth, Zn accumulation, and other physiological parameters were investigated. Subsequently, the rats were fed ZnO NP-biofortified lentil seedlings (20 and 160 ppm) to assess their impact on animal health and Zn status. The results highlighted a concentration-dependent response of lentil seedlings to ZnO NPs, with optimal growth observed at 20 ppm, whereas higher concentrations inhibited lentil growth. Pigment and biochemical analyses revealed a complex interplay between chlorophyll, carotenoids, soluble sugars, and proteins with distinct responses to nanoparticle concentrations. Elevated levels of hydrogen peroxide and malondialdehyde of lentil seedlings at high concentrations of ZnO NPs suggest oxidative stress, countered by the upregulation of antioxidant enzymes and increased phenolic compounds. On the other hand. animal studies have showed that ZnO NP-biofortified lentil seedlings enhance serum zinc and magnesium levels in rats without affecting body weight. While serum triglyceride levels of rats decreased in both treatment groups, an elevation in creatinine and a marked increase in aspartate aminotransferase (AST) levels were observed at a higher ZnO NP concentration (160 ppm), indicative of potential kidney and liver stress. Paradoxically, serum iron levels were lower in all groups consuming lentil seedlings than in the control group, suggesting a potential interaction between lentil components and iron metabolism. These findings suggest that ZnO NP-biofortified lentils may be a promising approach to enhance Zn nutrition; however, further investigation is needed to optimize ZnO NPs concentration and assess long-term safety., (© 2024. The Author(s).)

Coumarin, a naturally occurring compound found in various plants, has a rich history of use in traditional medicine. Recent research has highlighted its anti-inflammatory properties, positioning it as a promising candidate for treating inflammatory disorders such as rheumatoid arthritis, asthma, and inflammatory bowel disease. This narrative review aims to comprehensively summarize the current knowledge regarding coumarin's pharmacological effects in alleviating inflammatory conditions by analyzing preclinical and clinical studies. The review focuses on elucidating the mechanisms through which coumarin exerts its anti-inflammatory effects, including its antioxidant activity, inhibiting pro-inflammatory cytokine production, and modulation of immune cell functions. Additionally, the paper addresses potential limitations of using coumarin, such as concerns about toxicity at high doses or with prolonged use. Before widespread clinical application, further investigation is needed to fully understand coumarin's potential benefits and risks., Competing Interests: 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., (© 2024 The Authors. Published by Elsevier B.V.)

The Claisen self-condensation of lactones can be carried out safely and efficiently under Mukaiyama conditions, in the presence of TiCl 4 and triethylamine. The primary Claisen products can be elaborated to various derivatives or converted directly into dihydroxyketones. Such compounds are valuable educts for the synthesis of ionizable lipids for the delivery of nucleic acid therapeutics and can now be accessed through a concise, economical, scalable route that avoids more technically challenging reaction sequences.

Lipid nanoparticles (LNPs) have proven to be promising delivery vehicles for RNA-based vaccines and therapeutics, particularly in LNP formulations containing ionizable cationic lipids that undergo protonation/deprotonation in response to buffer pH changes. These nanoparticles are typically formulated using a rapid mixing technique at low pH, followed by a return to physiological pH that triggers LNP-LNP fusion. A detailed understanding of these dynamic processes is crucial to optimize the overall performance and efficiency of LNPs. However, knowledge gaps persist regarding how particle formation mechanisms impact drug loading and delivery functions. In this work, we employ single-molecule Convex Lens-induced Confinement (CLiC) microscopy in combination with Förster resonance energy transfer (FRET) measurements to study LNP fusion dynamics in relation to various formulation parameters, including lipid concentration, buffer conditions, drug loading ratio, PEG-lipid concentrations, and ionizable lipid selection. Our results reveal a strong correlation between the measured fusion dynamics and the formulation parameters used; these findings are consistent with DLS and Cryo-TEM-based assays. These measurements offer a cost-effective method for characterizing and screening potential drug candidates and can provide additional insights into their design, with opportunities for optimization.

Environmental pollution with plastic polymers has become a global problem, leaving no continent and habitat unaffected. Plastic waste is broken down into smaller parts by environmental factors, which generate micro- and nanoplastic particles (MNPPs), ultimately ending up in the human food chain. Before entering the human body, MNPPs make their first contact with saliva in the human mouth. However, it is unknown what proteins attach to plastic particles and whether such protein corona formation is affected by the particle's biophysical properties. To this end, we employed polystyrene MNPPs of two different sizes and three different charges and incubated them individually with saliva donated by healthy human volunteers. Particle zeta potential and size analyses were performed using dynamic light scattering complemented by nanoliquid chromatography high-resolution mass spectrometry (nLC/HRMS) to qualitatively and quantitatively reveal the protein soft and hard corona for each particle type. Notably, protein profiles and relative quantities were dictated by plastic particle size and charge, which in turn affected their hydrodynamic size, polydispersity, and zeta potential. Strikingly, we provide evidence of the latter to be dynamic processes depending on exposure times. Smaller particles seemed to be more reactive with the surrounding proteins, and cultures of the particles with five different cell lines (HeLa, HEK293, A549, HepG2, and HaCaT) indicated protein corona effects on cellular metabolic activity and genotoxicity. In summary, our data suggest nanoplastic size and surface chemistry dictate the decoration by human saliva proteins, with important implications for MNPP uptake in humans.

The environmental presence of nano- and micro-plastic particles (NMPs) is suspected to have a negative impact on human health. Environmental NMPs are difficult to sample and use in life science research, while commercially available plastic particles are too morphologically uniform. Additionally, this NMPs exposure exhibited biological effects, including cell internalization, oxidative stress, inflammation, cellular adaptation, and genotoxicity. Therefore, developing new methods for producing heterogenous NMPs as observed in the environment is important as reference materials for research. Thus, we aimed to generate and characterize NMPs suspensions using a modified ultrasonic protocol and to investigate their biological effects after exposure to different human cell lines. To this end, we produced polyethylene terephthalate (PET) NMPs suspensions and characterized the particles by dynamic light scattering and scanning electron microscopy. Ultrasound treatment induced polymer degradation into smaller and heterogeneous PET NMPs shape fragments with similar surface chemistry before and after treatment. A polydisperse suspension of PET NMPs with 781 nm in average size and negative surface charge was generated. Then, the PET NMPs were cultured with two human cell lines, A549 (lung) and HaCaT (skin), addressing inhalation and topical exposure routes. Both cell lines interacted with and have taken up PET NMPs as quantified via cellular granularity assay. A549 but not HaCaT cell metabolism, viability, and cell death were affected by PET NMPs. In HaCaT keratinocytes, large PET NMPs provoked genotoxic effects. In both cell lines, PET NMPs exposure affected oxidative stress, cytokine release, and cell morphology, independently of concentration, which we could relate mechanistically to Nrf2 and autophagy activation. Collectively, we present a new PET NMP generation model suitable for studying the environmental and biological consequences of exposure to this polymer., Competing Interests: Declaration of competing interest The authors declare no conflict of interest with regard to the publication of this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Photodynamic therapy (PDT) represents a non-invasive treatment strategy currently utilized in the clinical management of selected cancers and infections. This technique is predicated on the administration of a photosensitizer (PS) and subsequent irradiation with light of specific wavelengths, thereby generating reactive oxygen species (ROS) within targeted cells. The cellular effects of PDT are dependent on both the localization of the PS and the severity of ROS challenge, potentially leading to the stimulation of various cell death modalities. For many years, the concept of regulated cell death (RCD) triggered by photodynamic reactions predominantly encompassed apoptosis, necrosis, and autophagy. However, in recent decades, further explorations have unveiled additional cell death modalities, such as necroptosis, ferroptosis, cuproptosis, pyroptosis, parthanatos, and immunogenic cell death (ICD), which helps to achieve tumor cell elimination. Recently, nanoparticles (NPs) have demonstrated substantial advantages over traditional PSs and become important components of PDT, due to their improved physicochemical properties, such as enhanced solubility and superior specificity for targeted cells. This review aims to summarize recent advancements in the applications of different metal-based NPs as PSs or delivery systems for optimized PDT in cancer treatment. Furthermore, it mechanistically highlights the contribution of RCD pathways during PDT with metal NPs and how these forms of cell death can improve specific PDT regimens in cancer therapy., 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

Tyrosinase is the key enzyme for melanin biosynthesis. Overproduction and deposition of this pigment cause different problems in various industries including agriculture and food. Finding safe tyrosinase inhibitors thus attracts great research interest. The goal of this study is evaluation of inhibitory potencies of some novel synthetic derivatives of tyrosol and raspberry ketone on diphenolase activity of mushroom tyrosinase. The ligands inhibited enzyme activity and compound 4-(2-(4-(hydroxymethyl)-2-methyl-1,3-dioxolan-2-yl)ethyl)phenol (1d) exhibited the most inhibitory potency (77% inhibition, IC 50  = 0.32 µmol L -1 ) via the mixed inhibition mode. This compound was also safe according to the results of in vitro analyses. The enzyme-ligands interactions were theoretically and experimentally investigated using molecular docking and fluorescence quenching approaches, respectively. Modes of quenching and related parameters were also determined and molecular docking data showed that the ligands bind to important sites of the enzyme. These compounds, especially 1d, can be suggested as efficient candidates for further investigations., 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 Elsevier Ltd. All rights reserved.)

A multiferroic nanostructure of manganese ferrite barium-titanate called magneto-electric nanoparticles (MENs) was synthesized by a co-precipitation method. FTIR, Raman spectroscopy, TEM, and X-ray diffraction confirmed the presence of spinel core and perovskite shell phases with average crystallite sizes of 70-90 nm. Magnetic, optical, and magnetoelectrical properties of MENs were investigated using VSM, UV-Vis spectrophotometry, DLS, and EIS spectroscopy techniques. After pre-activation by low-pressure argon (Ar) plasma, the MENs were functionalized by a highly hydrophilic acrylic acid and Oxygen (AAc+O 2 ) mixture to produce COOH and C=O-rich surfaces. The loading and release of doxorubicin hydrochloride (DOX) on MENs were investigated using UV-vis and fluorescence spectrophotometry under alternating low-frequency magnetic fields. Plasma treatment enabled drug-loading control by changing the particles' roughness as physical adsorption and creating functional groups for chemical absorption. This led to reduced metabolic activity and cell adherences associated with elevated expression of pro-apoptotic genes (BCL-2, caspase 3) in 4T1 breast cancer cells in vitro exposed to alternating current magnetic field (ACMF) compared to MENs-DOX without field exposure. ACMF-potentiated anticancer effects of MENs were validated in vivo in tumor-bearing Balb/C mice. Altogether, our results suggest potentiated drug loading of MENs showing superior anticancer activity in vitro and in vivo when combined with ACMF., (© 2023. Springer Nature Limited.)

This study aimed to identify the indices/indicators used for evaluating the "creating supportive environments" mechanism of the Ottawa Charter for Health Promotion, with a focus on built environments, in different settings. A search for literature with no time limit constraint was performed across Medline (via PubMed), Scopus, and Embase databases. Search terms included "Ottawa Charter," "health promotion," "supportive environments," "built environments," "index," and "indicator." we included the studies conducted on developing, identifying, and/or measuring health promotion indices/indicators associated with "built environments" in different settings. The review articles were excluded. Extracted data included the type of instrument used for measuring the index/indicator, the number of items, participants, settings, the purpose of indices/indicators, and a minimum of two associated examples of the indices domains/indicators. The key definitions and summarized information from studies are presented in tables. In total, 281 studies were included in the review, within which 36 indices/indicators associated with "built environment" were identified. The majority of the studies (77%) were performed in developed countries. Based on their application in different settings, the indices/indicators were categorized into seven groups: (1) Healthy Cities (n=5), (2) Healthy Municipalities and Communities (n=18), (3) Healthy Markets (n=3), (4) Healthy Villages (n=1), (5) Healthy Workplaces (n=4), (6) Health-Promoting Schools (n=3), and (7) Healthy Hospitals (n=3). Health promotion specialists, health policymakers, and social health researchers can use this collection of indices/indicators while designing/evaluating interventions to create supportive environments for health in various settings.

Potentially inappropriate prescribing (PIP) is a major public health concern with several undesirable health consequences for older adults. In this overview, we aimed to map and gather information from existing literature to provide a better insight into the prevalence of PIP among community dwellers. Electronic databases were searched from their inception to April 2022. The quality of the included systematic reviews (SRs) was assessed using the assessment of multiple systematic reviews checklist. The degree of overlap within the SRs was also evaluated (2% overlap). All SRs on the prevalence of PIP in older individuals in community settings were included, and a narrative approach was used to synthesize data. Nineteen SRs comprising 548 primary studies met the inclusion criteria, and the average quality of the included SRs was moderate. More than half (50.5%) of the primary studies were conducted in Europe, followed by the United States (22.8%), and Asia (18.9%). Thirty different criteria were used in the primary studies to estimate the prevalence of PIP. The most widely used criteria were those presented in Beers (41.8%) and STOPP (Screening Tool of Older Persons' Prescriptions)/START (Screening Tool to Alert to Right Treatment) (21.8%) criteria. Benzodiazepines, nonsteroidal anti-inflammatory drugs, and antidepressants were the most frequently reported PIPs. A considerable variation in the prevalence of PIP ranging from 0% to 98% was reported by SRs. However, there is a high degree of uncertainty regarding the extent of PIP in community settings. To identify knowledge-to-action gaps, SR authors should consider the differences in prevalence of PIP according to settings, applied tools, data sources, geographical areas, and specific pathologies. There is also a need for primary and SR studies from low- and middle-income countries regarding the prevalence of PIP.

Introduction: Medical gas plasma therapy has been successfully applied to several types of cancer in preclinical models. First palliative tumor patients suffering from advanced head and neck cancer benefited from this novel therapeutic modality. The gas plasma-induced biological effects of reactive oxygen and nitrogen species (ROS/RNS) generated in the plasma gas phase result in oxidation-induced lethal damage to tumor cells., Objectives: This study aimed to verify these anti-tumor effects of gas plasma exposure on urinary bladder cancer., Methods: 2D cell culture models, 3D tumor spheroids, 3D vascularized tumors grown on the chicken chorion-allantois-membrane (CAM) in ovo, and patient-derived primary cancer tissue gas plasma-treated ex vivo were used., Results: Gas plasma treatment led to oxidation, growth retardation, motility inhibition, and cell death in 2D and 3D tumor models. A marked decline in tumor growth was also observed in the tumors grown in ovo. In addition, results of gas plasma treatment on primary urothelial carcinoma tissues ex vivo highlighted the selective tumor-toxic effects as non-malignant tissue exposed to gas plasma was less affected. Whole-transcriptome gene expression analysis revealed downregulation of tumor-promoting fibroblast growth factor receptor 3 (FGFR3) accompanied by upregulation of apoptosis-inducing factor 2 (AIFm2), which plays a central role in caspase-independent cell death signaling., Conclusion: Gas plasma treatment induced cytotoxicity in patient-derived cancer tissue and slowed tumor growth in an organoid model of urinary bladder carcinoma, along with less severe effects in non-malignant tissues. Studies on the potential clinical benefits of this local and safe ROS therapy are awaited., 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. Production and hosting by Elsevier B.V.)

Background: Type 2 diabetes mellitus (T2DM) is one of the most important risk factors for cardiovascular diseases, with a high economic burden on health care systems. Since gender and residency can affect people's lifestyle and health behaviors, this study was conducted to investigate the prevalence of T2DM and its determinants by gender and residency., Methods: A secondary analysis study was conducted on the survey data of the IraPEN (Iran's Package of Essential Non-Communicable Disease) pilot program conducted in 2017 in Naghadeh County, Iran. Data of 3,691 participants aged 30-70 years from rural and urban areas of the County were included into data analysis process. Sociodemographic factors, anthropometric measurements, and cardiovascular risk factors related to T2DM were assessed., Results: The overall prevalence of T2DM within the population was 13.8%, which was significantly higher among women (15.5%) than men (11.8%), and non-significantly higher in urban (14.5%) areas than rural (12.3%) areas. In both genders, age (male: OR 1.01, 95% CI: 1.00-1.03; P = 0.012; female: OR 1.03, 95% CI: 1.02-1.04; P<0.001), blood pressure (male: OR 1.77, 95% CI: 1.13-2.79; P = 0.013; female: OR 2.86, 95% CI: 2.12-3.85; P<0.001), and blood triglycerides (male: OR 1.46, 95% CI: 1.01-2.11; P = 0.04; female: OR 1.34, 95% CI: 1.02-1.77; P = 0.035) had a significant relationship with the chance of developing T2DM. Among women, a significant relationship was found between abdominal obesity (OR 1.68, 95% CI: 1.17-2.40; P = 0.004) and the chance of developing T2DM. Age (rural: OR 1.03, 95% CI: 1.01-1.04; P<0.001; urban: OR 1.02, 95% CI: 1.01-1.04; P<0.001), blood pressure (rural: OR 3.14, 95% CI: 2.0-4.93; P<0.001; urban: OR 2.23, 95% CI: 1.66-3; P<0.001), and abdominal obesity (rural: OR 2.34, 95% CI: 1.41-3.87; P = 0.001; urban: OR 1.46, 95% CI: 1.06-2.01; P = 0.019), in both rural and urban areas, blood cholesterol (OR 1.59, 95% CI: 1.07-2.37; P = 0.02) in rural areas, and blood triglycerides (OR 1.51, 95% CI: 1.16-1.98; P = 0.002) in urban areas were significant predictors of T2DM., Conclusion: Given the higher prevalence of T2DM among females, risk reduction strategies at the community level should be more targeted at women. The higher prevalence of T2DM risk factors among the urban population is a wake-up call for policymakers to pay more attention to the consequences of unhealthy and sedentary lifestyles within urban communities. Future actions should be focused on appropriate timely action plans for the prevention and control of T2DM from early years of life., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ghassab-Abdollahi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Nano- and microplastic particles (NMP) are strong environmental contaminants affecting marine ecosystems and human health. The negligible use of biodegradable plastics and the lack of knowledge about plastic uptake, accumulation, and functional consequences led us to investigate the short- and long-term effects in freshly isolated skin cells from mice. Using fluorescent NMP of several sizes (200 nm to 6 µm), efficient cellular uptake was observed, causing, however, only minor acute toxicity as metabolic activity and apoptosis data suggested, albeit changes in intracellular reactive species and thiol levels were observed. The internalized NMP induced an altered expression of various targets of the nuclear factor-2-related transcription factor 2 pathway and were accompanied by changed antioxidant and oxidative stress signaling responses, as suggested by altered heme oxygenase 1 and glutathione peroxide 2 levels. A highly increased beta-catenin expression under acute but not chronic NMP exposure was concomitant with a strong translocation from membrane to the nucleus and subsequent transcription activation of Wnt signaling target genes after both single-dose and chronic long-term NMP exposure. Moreover, fibroblast-to-myofibroblast transdifferentiation accompanied by an increase of α smooth muscle actin and collagen expression was observed. Together with several NMP-induced changes in junctional and adherence protein expression, our study for the first time elucidates the acute and chronic effects of NMP of different sizes in primary skin cells' signaling and functional biology, contributing to a better understanding of nano- and microplastic to health risks in higher vertebrates., (© 2023. The Author(s).)

The ubiquitous nature of microplastic particles (MP) is a growing environmental and ecological concern due to their impact on aquatic and terrestrial systems and potentially on human health. The potential impact on human health may be due to MP daily exposure by several routes, but little is known about the cellular effects. Previous in vitro and in vivo studies have described inflammation, oxidative stress, and metabolic disruption upon plastic exposure, while the effect of individual plastic parameters is not fully unraveled. To this end, we investigated plastic exposure to different polymer types, sizes, and concentrations in three human cell lines (A549, HEK293, and HeLa). Particles were polystyrene (PS) or polymethylmethacrylate (PMMA) in three sizes and concentrations, and amine-modified PS served as positive control. After MP size validation using dynamic light scattering, a high-throughput high-content imaging-based and algorithm-driven multi-z-stack analysis was established to quantify intracellular fluorescent particle accumulation in 3D objects and cell maximum intensity projections. MP uptake correlated with concentration and for PS with size (1.040 μm), while for PMMA it was maximal for 400 nm MP. Uptake increased in HEK cells independent of MP parameters. Except for positive controls, no major effect on metabolic activity, viability, and cell cycle was observed, while intracellular thiol content and cytokine secretion were affected to a considerable extent. Interestingly, particle uptake was correlated significantly with particle size and concentration, underlining the dependence of MP parameters on biological effects., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Research on nano- and micro-plastic particles (NMPPs) suggests their potential threat to human health. Some studies have even suggested genotoxic effects of NMPP exposure, such as micronuclei (MN) formation, while others found the opposite. To clarify the ability of NMPP to induce MN formation, we used non-malignant HaCaT keratinocytes and exposed these to a variety of polystyrene (PS) and poly methyl methacrylate (PMMA) particle types at different concentrations and three different sizes. Investigations were performed following acute (one day) and chronic exposure (five weeks) against cytotoxic (amino-modified NMPPs) and genotoxic (methyl methanesulfonate, MMS) positive controls. An optimized high-content imaging workflow was established strictly according to OECD guidelines for analysis. Algorithm-based object segmentation and MN identification led to computer-driven, unsupervised quantitative image analysis results on MN frequencies among the different conditions and thousands of cells per condition. This could only be realized using accutase, allowing for partial cell detachment for optimal identification of bi-nucleated cells. Cytotoxic amino-modified particles were not genotoxic; MMS was both. During acute and long-term studies, PS and PMMA particles were neither toxic nor increased MN formation, except for 1000 nm PS particles at the highest concentration of unphysiological 100 µg/mL. Interestingly, ROS formation was significantly decreased in this condition. Hence, most non-charged polymer particles were neither toxic nor genotoxic, while aminated particles were toxic but not genotoxic. Altogether, we present an optimized quantitative imaging workflow applied to a timely research question in environmental toxicity.

Tyrosinase plays determinant role in enzymatic browning of vegetables and fresh-cut fruits. Development of new tyrosinase inhibitors is of great concern in food and agriculture. To discover new inhibitors, novel phenolic derivatives were synthesized and their inhibitory effects were investigated on activity of mushroom tyrosinase. All compounds showed potent inhibitory activities in their low concentrations and compound 4-(4-hydroxyphenyl)butan-2-one (1b) was found to be the most potent inhibitor (73.75% inhibition, IC 50 value 5.6 μmol L -1 ). This ligand inhibited enzyme activity in a mixed pattern and kinetic parameters were also determined. In vitro assays revealed that this compound has not cytotoxicity/hemolytic effects and can be considered as safe for further investigations. Analysis of fluorescence spectra showed that all ligands quenched enzyme intrinsic fluorescence. The quenching mode and important binding parameters were also calculated. Enzyme-ligands interactions were also theoretically analyzed by molecular docking and results showed that the ligands interact with structurally/functionally critical residues., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

A group of biosurfactants, called rhamnolipids, have been shown to have antibacterial and antibiofilm activity against multidrug-resistant bacteria. Here, we examined the effect of rhamnolipid biosurfactants extracted from Pseudomonas aeruginosa MA01 on cell growth/viability, biofilm formation, and membrane permeability of methicillin-resistant Staphylococcus aureus (MRSA) ATCC6538 bacterial cells. The results obtained from flow cytometry analysis showed that by increasing the concentration of rhamnolipid from 30 to 120 mg/mL, the cell viability decreased by about 70%, and the cell membrane permeability increased by approximately 20%. In fact, increasing rhamnolipid concentration was directly related to cell membrane permeability and inversely related to cell survival. Microtiter plate biofilm assay and laser scanning confocal microscopy analysis revealed that rhamnolipid, at a concentration of 60 mg/mL, exerts a reducing effect on the biofilm formation of Staphylococcus aureus. Real-time PCR analysis for monitoring the relative changes in the expression of agrA, agrC, icaA, and icaD genes involved in biofilm formation and related to the quorum-sensing pathway after treatment with rhamnolipid indicated a reduced expression level of these genes, as well as sortase A gene. The results of the present study deepen our knowledge regarding the use of microbial natural products as promising candidates for therapeutic applications., (© 2022. The Author(s).)

This paper describes a synthesis of ALC-0315 by a sequence that more than doubles the overall yield relative to the published one, and that employs much cleaner reactions, thereby facilitating purifications to a considerable extent., (© 2022 Wiley-VCH GmbH.)

Despite therapeutic improvements in recent years, breast cancer remains an often fatal disease. In addition, breast cancer ulceration may occur during late stages, further complicating therapeutic or palliative interventions. In the past decade, a novel technology received significant attention in the medical field: gas plasma. This topical treatment relies on the partial ionization of gases that simultaneously produce a plethora of reactive oxygen and nitrogen species (ROS/RNS). Such local ROS/RNS overload inactivates tumour cells in a non-necrotic manner and was recently identified to induce immunogenic cancer cell death (ICD). ICD promotes dendritic cell maturation and amplifies antitumour immunity capable of targeting breast cancer metastases. Gas plasma technology was also shown to provide additive toxicity in combination with radio and chemotherapy and re-sensitized drug-resistant breast cancer cells. This work outlines the assets of gas plasma technology as a novel tool for targeting breast cancer by summarizing the action of plasma devices, the roles of ROS, signalling pathways, modes of cell death, combination therapies and immunological consequences of gas plasma exposure in breast cancer cells in vitro, in vivo, and in patient-derived microtissues ex vivo., (© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Objective: To determine 1) the indexes/indicators used for evaluating the "strengthening community actions" mechanism of the Ottawa Charter for Health Promotion and 2) to extract the characteristics and key components of the indexes/indicators using a scoping review. Data Source :In May 2020, the search was conducted across three databases: Medline (via PubMed), Embase, and Scopus. Inclusion and Exclusion Criteria : All primary studies relating to development, identification, and measurement of health promotion indices/indicators associated to the "strengthening community actions" were included. The review articles were excluded., Data Extraction: The data were extracted to a data-charting form that was developed by the research team. Two authors reviewed the extracted data., Data Synthesis: To summarize and report the data, a descriptive numerical analysis and a narrative descriptive synthesizing approach were used., Results: In total, 93 study articles were included. A majority of studies (82%) were conducted in developed countries. Different types of recognized indices were categorized into seven groups: social cohesion (n = 3), community capacity (n = 1), community participation (n = 7), social capital (n = 6), social network (n = 3), social support (n = 1), and others (n = 5)., Conclusions: Having a collection of "strengthening community actions" indices/indicators in hand, health policymakers and health promotion specialists might be able to do their best in considering, selecting, and applying the most appropriate indices/indicators while evaluating community health promotion interventions in different settings.

Intraoperative radiotherapy (IORT) could abrogate cancer recurrences, but the underlying mechanisms are unclear. To clarify the effects of IORT-induced wound fluid on tumor progression, we treated breast cancer cell lines and human-derived tumor spheroids in 2D and microfluidic cell culture systems, respectively. The viability, migration, and invasion of the cells under treatment of IORT-induced wound fluid (WF-RT) and the cells under surgery-induced wound fluid (WF) were compared. Our findings showed that cell viability was increased in spheroids under both WF treatments, whereas viability of the cell lines depended on the type of cells and incubation times. Both WFs significantly increased sub-G1 and arrested the cells in G0/G1 phases associated with increased P16 and P21 expression levels. The expression level of Caspase 3 in both cell culture systems and for both WF-treated groups was significantly increased. Furthermore, our results revealed that although the migration was increased in both systems of WF-treated cells compared to cell culture media-treated cells, E-cadherin expression was significantly increased only in the WF-RT group. In conclusion, WF-RT could not effectively inhibit tumor progression in an ex vivo tumor-on-chip model. Moreover, our data suggest that a microfluidic system could be a suitable 3D system to mimic in vivo tumor conditions than 2D cell culture., (© 2022. The Author(s).)

The pandemic has posed an intense threat to the mental health of younger adults. Despite significant efforts in studying various aspects of COVID-19, there is a dearth of evidence on how negative emotions are associated with behaviors. A comparison across associated factors to different negative emotions by means of a unified model is especially missing from the literature. This study was conducted by using the results of a survey conducted across 2,534 students enrolled in 7 states in the US. Various feelings such as sad, irritable, stress and guilt were analyzed in a unified model by means of seemingly unrelated regression (SUR). Questions were asked related to rationally limiting the spread of virus, and questions related to behaviors that seem to be extreme. Irrational behaviors, such as limiting exercise at home due to COVID-19 could be due to experiencing negative emotions, which distort the meaning of events for the students. That behavior, for instance, was found to be positively associated with various negative feelings. In addition, the results highlighted significant differences across emotions in terms of demographic characteristics such as gender and age, and various precautionary actions that students take, such as limiting outdoor activities or limiting social gathering. For instance, it was highlighted while avoiding a large group of people, in spite of its importance in curbing the spread of virus, is negatively associated with various negative emotions, taking a possible nonconsequential precaution of completely limiting all people outside the immediate family result in a higher level of negative emotions. Also, it was found that having a higher body mass index (BMI), self-rated worse health conditions, and limiting outdoor activities have detrimental effects on the mental health of students., Competing Interests: The authors have declared that no competing interests exist.

Glioblastoma multiforme (GBM) is the most common primary malignant adult brain tumor. Therapeutic options for glioblastoma are maximal surgical resection, chemotherapy, and radiotherapy. Therapy resistance and tumor recurrence demand, however, new strategies. Several experimental studies have suggested gas plasma technology, a partially ionized gas that generates a potent mixture of reactive oxygen species (ROS), as a future complement to the existing treatment arsenal. However, aspects such as immunomodulation, inflammatory consequences, and feasibility studies using GBM tissue have not been addressed so far. In vitro, gas plasma generated ROS that oxidized cells and led to a treatment time-dependent metabolic activity decline and G2 cell cycle arrest. In addition, peripheral blood-derived monocytes were co-cultured with glioblastoma cells, and immunomodulatory surface expression markers and cytokine release were screened. Gas plasma treatment of either cell type, for instance, decreased the expression of the M2-macrophage marker CD163 and the tolerogenic molecule SIGLEC1 (CD169). In patient-derived GBM tissue samples exposed to the plasma jet kINPen ex vivo, apoptosis was significantly increased. Quantitative chemokine/cytokine release screening revealed gas plasma exposure to significantly decrease 5 out of 11 tested chemokines and cytokines, namely IL-6, TGF-β, sTREM-2, b-NGF, and TNF-α involved in GBM apoptosis and immunomodulation. In summary, the immuno-modulatory and proapoptotic action shown in this study might be an important step forward to first clinical observational studies on the future discovery of gas plasma technology's potential in neurosurgery and neuro-oncology especially in putative adjuvant or combinatory GBM treatment settings.

Reactive oxygen species (ROS) have been subject of increasing interest in the pathophysiology and therapy of cancers in recent years. In skin cancer, ROS are involved in UV-induced tumorigenesis and its targeted treatment via, e.g., photodynamic therapy. Another recent technology for topical ROS generation is cold physical plasma, a partially ionized gas expelling dozens of reactive species onto its treatment target. Gas plasma technology is accredited for its wound-healing abilities in Europe, and current clinical evidence suggests that it may have beneficial effects against actinic keratosis. Since the concept of hormesis dictates that low ROS levels perform signaling functions, while high ROS levels cause damage, we investigated herein the antitumor activity of gas plasma in non-melanoma skin cancer. In vitro, gas plasma exposure diminished the metabolic activity, preferentially in squamous cell carcinoma cell (SCC) lines compared to non-malignant HaCaT cells. In patient-derived basal cell carcinoma (BCC) and SCC samples treated with gas plasma ex vivo, increased apoptosis was found in both cancer types. Moreover, the immunomodulatory actions of gas plasma treatment were found affecting, e.g., the expression of CD86 and the number of regulatory T-cells. The supernatants of these ex vivo cultured tumors were quantitatively screened for cytokines, chemokines, and growth factors, identifying CCL5 and GM-CSF, molecules associated with skin cancer metastasis, to be markedly decreased. These findings suggest gas plasma treatment to be an interesting future technology for non-melanoma skin cancer topical therapy.

While many new and emerging therapeutic concepts have appeared throughout the last decades, cancer still is fatal in many patients. At the same time, the importance of immunology in oncotherapy is increasingly recognized, not only since the advent of checkpoint therapy. Among the many types of tumors, also breast cancer has an immunological dimension that might be exploited best by increasing the immunogenicity of the tumors in the microenvironment. To this end, we tested a novel therapeutic concept, gas plasma irradiation, for its ability to promote the immunogenicity and increase the toxicity of breast cancer cells in vitro and in vivo. Mechanistically, this emerging medical technology is employing a plethora of reactive oxygen species being deposited on the target cells and tissues. Using 2D cultures and 3D tumor spheroids, we found gas plasma-irradiation to drive apoptosis and immunogenic cancer cell death (ICD) in vitro, as evidenced by an increased expression of calreticulin, heat-shock proteins 70 and 90, and MHC-I. In 4T1 breast cancer-bearing mice, the gas plasma irradiation markedly decreased tumor burden and increased survival. Interestingly, non-treated tumors injected in the opposite flank of mice exposed to our novel treatment also exhibited reduced growth, arguing for an abscopal effect. This was concomitant with an increase of apoptosis and tumor-infiltrating CD4 + and CD8 + T-cells as well as dendritic cells in the tissues. In summary, we found gas plasma-irradiated murine breast cancers to induce toxicity and augmented immunogenicity, leading to reduced tumor growth at a site remote to the treatment area., (© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.)

In this study a novel method was implemented and investigated in order to destroy cancer cells inside the mouse body on a clinical level. In the case of in-vitro study, MTT assay was employed to discover an effective dose of applied plasma and distinguish the plasma effect in direct and in indirect treatments. Tumor growth was also measured in in-vivo section so that the effectiveness of direct and indirect treatments could be compared. Furthermore, an investigation was conducted to study the interferences between a conventional method (chemotherapy) and plasma treatment so as to increase the effectiveness of treatment inside the body. Hematoxylin and Eosin, Flow Cytometry, TUNEL and Western Blot assay were used to investigate any cell alteration and the impact of various treatment methods on cancer cell and amount of their apoptosis and protein levels. Radiology and CT scan images were taken to determine the final tumor volume. The results showed a significant cell death and substantial reduction in tumor growth in direct plasma treatment in comparison with indirect plasma treatment. Eventually, dramatic destruction of cancer cells was observed while using of indirect plasma-chemotherapy combination, thus introducing an effective method for deep tissue tumors can be introduced.

Gold nanoparticles supported on imidazole-modified bentonite, Bent@Im@Au NPs, has been developed for the first time as an effective heterogeneous catalyst for the synthesis of propargylamines under mild reaction conditions in water at a loading of 0.07 mol % of Au. Various techniques such as X-ray diffraction, high-resolution transmission electron microscopy, Fourier transform infrared spectroscopy, and element mapping by scanning electron microscopy were used to determine the physicochemical properties of the catalysts. The new gold catalyst was found to be highly active providing high to excellent yields of A3 coupling products via the reactions of various aldehydes, having electron-withdrawing as well as electron-donating substituents, with different amines and alkynes. The catalysts can be easily recovered and reused without significant loss of activity and the recycled catalyst was characterized., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Sleep is one of the most basic human requirements. This research aims at determining the status of sleep quality and its relationship with quality of life among high-risk pregnant women in Tabriz, Iran, in 2015., Materials and Methods: This research was a sectional study done on 364 qualified women in 28-36 weeks of pregnancy suffering from mild preeclampsia and gestational diabetes. The sampling was done as convenience. Personal-social-midwifery questionnaire, Pittsburg sleep quality, and quality of life in pregnancy (QOL-ORAV) were used for gathering data. Multivariate linear regression model was used for determining the relationship between sleep quality and its subsets with quality of life and controlling confounders., Findings: In the current study, the prevalence of sleep disturbance was 96.4%. Mean (SD) of the total score of sleep quality was 10.1 (4.1) and the total score of quality of life was 61.7 (17.3). According to Pearson's correlation test, there was statistically significant relationship between quality of life and sleep quality and all its subsets except sleep duration and use of sleep medication (p < 0.001). Meanwhile, according to the multivariate linear regression model, sleep latency, day time dysfunction, health status, and home air-conditioning were related with quality of life., Discussion: The findings of current research show that sleep quality is low among high-risk pregnant women and quality of life is medium. So, it is necessary that required training is given by health cares for improving sleep quality and quality of life to mothers.

Background: Different diagnostic screening tests have been developed to detect periodontal disease in the early stages. Despite these advances still, there is a need for a more practical and beneficial diagnostic test., Aim: The aim of this study was to investigate the possibility of developing such a kit based on the body immune response against Porphyromonas gingivalis., Method and Materials: This experimental study was conducted by culturing P. gingivalis and extracting its antigens. These antigens were injected into peritoneal cavity of four Balb/c mice. Finally, the pattern, type, and quantity of antibody response against P. gingivalis antigen were detected. Results of the study showed that 3.0 × 108 cells of P. gingivalis are an appropriate count for stimulating the immunization in Balb/c mice and the subsequent amount of antibody (IgG) production was 81.5 μg/ml., Result: The antigenic injections which were done in the current study could mimic the condition of periodontal disease and the raise of P. gingivalis in the body., Conclusion: The obtained data can be used in future attempts to develop practical and usable test kits against P. gingivalis.

An enzyme free glucose sensor was prepared by a molecular imprinting method (MIP). The procedure was developed by in situ preparation of a new polyvinyl acetate (PVA) electrode reinforced by MnO2/CuO loaded on graphene oxide (GO) nanoparticles (PVA/MnO2@GO/CuO). The nanocomposite was modified in the presence of glucose and then imprinted. A carbone paste method with voltammetry was used in the fabrication of the sensor from prepared MIP nanocomposite. PVA/MnO2@GO/CuO electrode was characterized by X-ray diffraction, FT-IR spectroscopy and scanning electron microscopy. Electrocatalytic activity of the electrode toward glucose oxidation was then investigated by cyclic voltammetry in alkaline medium. The results show that the response of PVA/MnO2@GO/CuO MIP is much higher than PVA/MnO2@GO/CuO non-imprinted electrode toward glucose oxidation. The detection limit was 53μM, and the sensor responses are linear for concentrations from 0.5 to 4.4mM. Relative standard deviations for intra- and inter-day determination were less than 6.0%. The relative recoveries for different samples were 96%., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Because students' ability to use statistics, which is mathematical in nature, is one of the concerns of educators, embedding within an e-learning system the pedagogical characteristics of learning is 'value added' because it facilitates the conventional method of learning mathematics. Many researchers emphasize the effectiveness of cognitive apprenticeship in learning and problem solving in the workplace. In a cognitive apprenticeship learning model, skills are learned within a community of practitioners through observation of modelling and then practice plus coaching. This study utilized an internet-based Cognitive Apprenticeship Model (i-CAM) in three phases and evaluated its effectiveness for improving statistics problem-solving performance among postgraduate students. The results showed that, when compared to the conventional mathematics learning model, the i-CAM could significantly promote students' problem-solving performance at the end of each phase. In addition, the combination of the differences in students' test scores were considered to be statistically significant after controlling for the pre-test scores. The findings conveyed in this paper confirmed the considerable value of i-CAM in the improvement of statistics learning for non-specialized postgraduate students.

Background: Periodontal disease is considered as a risk factor for poor pregnancy outcomes, including preterm birth and low birth weight. Only few studies have assessed the knowledge and practice behaviours of healthcare providers, concerning oral health during pregnancy, periodontal diseases and their role in adverse pregnancy outcomes. The present study aimed to compare the knowledge and practice behaviours of a group of Iranian obstetricians, general practitioners, and midwives about periodontal disease., Design and Methods: A cross-sectional study was conducted using a self-administered, structured questionnaire that was previously used in North Carolina. The questionnaire was translated into Persian language and was randomly distributed among 200 obstetricians, general practitioners, and midwives participating in an international congress. Data were analysed by Chi-square and spearman correlation tests using SPSS statistical software (version PASW 18)., Results: A total of 150 completed the questionnaires, achieving a response rate of 75%. Totally, the knowledge of the obstetricians was more accurate compared to the two other groups and the midwives were the worst. More experienced general practitioners (P=0.002) and obstetricians (P=0.049) did less dental examinations for their patients during their first visit or periodically. More experienced obstetricians also referred their patients for dental examinations during pregnancy less than their less experienced colleagues (P<0.001)., Conclusions: Although the participants had some knowledge about periodontal disease and its association with adverse pregnancy outcomes, there is much space for improvements. The participants' attitude and knowledge were consistent. Significance for public healthPreterm labour and low birth weight are considered to be one of the greatest problems in obstetrical medicine and are one of the most prevalent risk factors for death during the neonatal period. On the other hand, periodontal diseases are considered as important factors affecting pregnant women and their new-born children. Therefore it seems quite important to find out whether the healthcare providers who are most visited by pregnant women are aware of the periodontal disease and its relationship with poor pregnancy outcomes. The present study aimed to assess and compare the knowledge and beliefs of a group of Iranian obstetricians, general practitioners, and midwives regarding periodontal disease, and to assess whether their practice behaviours reflected their beliefs. The authors hope that publication of this paper would provide an evidence to plan for these health professionals' education on the importance of pregnant women's oral health promotion.

In the current study the effects of serine proteinase inhibitors (TLCK, TPCK, SBTI, and a combination of SBTI and TPCK) with concentrations of 1% and 4% of dietary protein in artificial diets were tested against growth of the Sunn pest, Eurygaster integriceps Puton (Hemiptera: Scutelleridae), development, and its gut serine proteinase targets. Analysis of variance indicated that protease inhibitors affected nymphal development time, adult weight, and survival. Mean development time of third instar nymphs in control, SBTI (1%), TLCK (1%), and TPCK was 7.18, 9.74, 9.97, and 8.52 days, respectively. The highest mortality (100 % mortality) was observed when a combination of TPCK and SBTI, both at 4% of dietary protein, was used followed by TPCK (4%) that produced 95% mortality. There were significant differences in proteinase activity between treatments and controls when BApNA and SAAPFpNA were used as substrates for trypsin and chymotrypsin, respectively. Reduction of trypsin activity in insects fed with low doses of SBTI (1%), TLCK (1%), and both doses of TPCK (1% and 4%) was 40, 26, 23, and 17%, respectively. Inhibition of chymotrypsin activity was seen in the insects fed on SBTI (1%), TLCK (1%), and TPCK (4%) where inhibition was 14, 9, and 36%, respectively. Maximum inhibition of chymotrypsin activity was observed in the insects fed on diets containing high doses of TPCK (4%). In gel assays, the greatest effects were observed when E. integriceps were fed on high doses of SBTI and TPCK. Therefore, TPCK followed by SBTI proved to be the most effective proteinase inhibitors of E. integriceps.

The effect of triticale α-amylases inhibitors on starch hydrolysis catalyzed by the Sunn pest, Eurygaster integriceps Puton (Hemiptera: Scutelleridae) midgut amylases was examined. Biochemical studgawies showed that inhibitors from Triticale (a hybrid of wheat and rye) had inhibitiory effects on E. integriceps α-amylases. The effects of the triticale α-amylase inhibitor (T-αAI) on α-amylase of E. integriceps showed a dose dependent manner of inhibition, e.g. less inhibition of enzyme activity (around 10%) with a lower dose (0.25 mg protein) and high inhibition of enzyme activity (around 80%) when a high dose of inhibitor was used (1.5 mg protein). The enzyme kinetic studies using Michaelis-Menten and Lineweaver-Burk equations showed the K(m) remained constant (0.58%) but the maximum velocity (V(max)) decreased in the presence of a crude extract of Triticale inhibitors, indicating mixed inhibition. The temperature giving 50% inactivation of enzyme (T(50)) during a 30-min incubation at pH 7.0 was 73° C. The maximum inhibitory activity was achieved at 35° C and pH 5.0. Gel assays showed the meaningful inhibition of E. integriceps α-amylases by various concentrations of Triticale inhibitors. Based on the data presented in this study, it could be said that the T-αAI has good inhibitory activity on E. integriceps gut α-amylase.