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Neuroinflammation stands as a critical player in the pathogenesis of diverse neurological disorders, with microglial cells playing a central role in orchestrating the inflammatory landscape within the central nervous system. Cannabidiol (CBD) has gained attention for its potential to elicit anti-inflammatory responses in microglia, offering promising perspectives for conditions associated with neuroinflammation. Here we investigated whether the NLRP3 inflammasome and inducible nitric oxide synthase (iNOS) are involved in the protective effects of CBD, and if their modulation is dependent on cannabinoid receptor 2 (CB2) and PPARγ signalling pathways. We found that treatment with CBD attenuated pro-inflammatory markers in lipopolysaccharide (LPS)-challenged BV2 microglia in a CB2- and PPARγ-dependent manner. At a molecular level, CBD inhibited the LPS-induced pro-inflammatory responses by suppressing iNOS and NLRP3/Caspase-1-dependent signalling cascades, resulting in reduced nitric oxide (NO), interleukin-1β (IL-1β), and tumour necrosis factor-alpha (TNF-α) concentrations. Notably, the protective effects of CBD on NLRP3 expression, Caspase-1 activity, and IL-1β concentration were partially hindered by the antagonism of both CB2 receptors and PPARγ, while iNOS expression and NO secretion were dependent exclusively on PPARγ activation, with no CB2 involvement. Interestingly, CBD exhibited a protective effect against TNF-α increase, regardless of CB2 or PPARγ activation. Altogether, these findings indicate that CB2 receptors and PPARγ mediate the anti-inflammatory effects of CBD on the NLRP3 inflammasome complex, iNOS activity and, ultimately, on microglial phenotype. Our results highlight the specific components responsible for the potential therapeutic applications of CBD on neuroinflammatory conditions.

Electrical and electronic equipment (EEE) have revolutionized our lives, however, their associated waste (WEEE) presents a global challenge because at this time EEE relies heavily on metals that are not commonly found in the living environment (Biosphere), which find their way into the environment during both production/disposal of EEE/WEEE. The use of organic components in EEE is increasingly common, particularly with the growing interest in flexible electronics. Here we describe an approach to device design employing in silico toxicity screening to assess the toxicity of the components chosen for use in EEE that is exemplified using inorganic and organic components known in the literature for the production of prototype organic light-emitting electrochemical cells. This approach could easily be employed to screen a variety of components for which datasets to produce safety data sheets (SDSs) don't yet exist because they have not been produced in large scale or in a regulatory environment which necessitates this. The approach has significant potential to improve high throughput screening of components for EEE that are "safe-by-design", potentially in combination with AI and ML approaches.

Colorectal cancer (CRC) is the second global cause of cancer morbidity. Often, potent CRC drugs fail to reach the market, due to the molecule having low solubility levels. Therefore, there is a need to develop a viable, targeted delivery system for hydrophobic drugs. Whey protein isolate (WPI), in the form of hydrogels, has demonstrated loadability with hydrophobic molecules. Hydrophobic cannabidiol (CBD) has demonstrated potential in inhibiting and suppressing CRC tumour growth. Therefore, in this study, WPI hydrogels were assessed as a novel oral hydrophobic drug delivery vehicle, using CBD as a model drug. The hydrogels were analysed in conditions consistent with the alimentary tract. The investigation was performed at pH 2 (stomach), pH 7 (small intestines) and pH 9 (large intestines) and using the enzymes pepsin (stomach) and protease (small and large intestines) to simulate the digestive environment. Polymer swelling assays demonstrated that the swelling potential of the hydrogels was strongly dependent on pH. At pH 2, hydrogels decreased in mass, losing around 10% of their initial mass, while hydrogels in a pH 9 environment increased in mass by approximately 50%. However, the enzymatic degradation of the hydrogels at pH 2 (pepsin, stomach), pH 7 (protease, small intestines) and pH 9 (protease, large intestines) was more pronounced in the neutral-alkaline pH range. Pepsin at pH 2 had no significant effect on the hydrogels. In contrast, protease at pH 9 significantly degraded the hydrogels, resulting in a mass loss of 30-40% from the initial mass. The results suggesting a higher rate of degradation in the intestines rather than in the stomach. Furthermore, CBD release, analysed with U.V. spectroscopy, demonstrated a higher release rate in pH conditions associated with the intestines (pH 7 and pH 9) rather than the stomach (pH 2), suggesting a higher rate of CBD release in regions of the digestive tract affected by CRC. Significantly, the hydrogels significantly reduced the viability of HT29 CRC cells. This study demonstrates the potential of the utilisation of WPI hydrogels as an oral hydrophobic drug delivery system.

Around 3% of children worldwide are affected by food allergy and its prevention is a public health priority. Dietary approaches have been shown to be effective in protecting against development of food allergy. While there is uncertainty for the effectiveness of dietary approaches implemented during pregnancy and breastfeeding to prevent allergy, early active introduction of common allergen foods in the infant diet is recommended as an effective approach for allergy prevention. There are challenges to uptake and putting the recommendations into practice; this article provides practical information to support families and health care professionals with implementing allergy prevention guidance.

Fatty acid binding protein 5 (FABP5, or epidermal FABP) is an intracellular chaperone of fatty acid molecules that regulates lipid metabolism and cell growth. In patient-derived tumours, FABP5 expression is increased up to tenfold, often co-expressed with other cancer-related proteins. High tumoral FABP5 expression is associated with poor prognosis. FABP5 activates transcription factors (TFs) leading to increased expression of proteins involved in tumorigenesis. Genetic and pharmacological preclinical studies show that inhibiting FABP5 reduces protumoral markers, whereas elevation of FABP5 promotes tumour growth and spread. Thus, FABP5 might be a valid target for novel therapeutics. The evidence base is currently strongest for liver, prostate, breast, and brain cancers, and squamous cell carcinoma (SCC), which could represent relevant patient populations for any drug discovery programme.

Osseous disease accounts for over half of chronic pathologies, but there is a limited supply of autografts, the gold standard; hence, there is a demand for new synthetic biomaterials. Herein, we present the use of a promising, new dairy-derived biomaterial: whey protein isolate (WPI) in the form of hydrogels, modified with the addition of different concentrations of the biotechnologically produced protein-like polymeric substance poly-γ-glutamic acid (γ-PGA) as a potential scaffold for tissue regeneration. Raman spectroscopic analysis demonstrated the successful creation of WPI-γ-PGA hydrogels. A cytotoxicity assessment using preosteoblastic cells demonstrated that the hydrogels were noncytotoxic and supported cell proliferation from day 3 to 14. All γ-PGA-containing scaffold compositions strongly promoted cell attachment and the formation of dense interconnected cell layers. Cell viability was significantly increased on γ-PGA-containing scaffolds on day 14 compared to WPI control scaffolds. Significantly, the cells showed markers of osteogenic differentiation; they synthesised increasing amounts of collagen over time, and cells showed significantly enhanced alkaline phosphatase activity at day 7 and higher levels of calcium for matrix mineralization at days 14 and 21 on the γ-PGA-containing scaffolds. These results demonstrated the potential of WPI-γ-PGA hydrogels as scaffolds for bone regeneration.

Purpose of the Review The purpose of the review is to review the evidence for the nutritional management of paediatric food allergy and provide a practical approach for healthcare professionals working in this area. Recent Findings Dietary elimination remains the mainstay for management of food allergies in children. However, the elimination of food allergens increases the risk for growth faltering, micronutrient deficiencies and feeding difficulties. Breastmilk remains the ideal source of nutrition for infants, but when not available, the vast majority will tolerate an extensively hydrolysed formula, and rice hydrolysate has also been suggested as a suitable alternative. Only in severe cases, including anaphylaxis, eosinophilic oesophagitis and growth faltering, is an amino acid formula indicated. The early introduction of peanut and egg and avoiding the delay in the introduction of other allergens, when not already allergic, has been highlighted by recent studies. Summary Whilst the elimination of allergens increases the risk of developing poor growth, micronutrient deficiencies and feeding difficulties, optimal, early dietary input, including advice on active introduction of allergens and alternative feeds, ideally from a registered dietitian/nutritionist, may be prevent and improve outcomes.

For some professionally, vocationally, or technically oriented careers, curricula delivered in higher education establishments may focus on teaching material related to a single discipline. By contrast, multidisciplinary, interdisciplinary, and transdisciplinary teaching (MITT) results in improved affective and cognitive learning and critical thinking, offering learners/students the opportunity to obtain a broad general knowledge base. Chemistry is a discipline that sits at the interface of science, technology, engineering, mathematics, and medicine (STEMM) subjects (and those aligned with or informed by STEMM subjects). This article discusses the significant potential of inclusion of chemistry in MITT activities in higher education and the real-world importance in personal, organizational, national, and global contexts. It outlines the development and implementation challenges attributed to legacy higher education infrastructures (that call for creative visionary leadership with strong and supportive management and administrative functions), and curriculum design that ensures inclusivity and collaboration and is pitched and balanced appropriately. It concludes with future possibilities, notably highlighting that chemistry, as a discipline, underpins industries that have multibillion dollar turnovers and employ millions of people across the world.

Electrical stimulation (ES) can serve as a therapeutic modality accelerating the healing of wounds, particularly chronic wounds which have impaired healing due to complications from underlying pathology. This review explores how ES affects the cellular mechanisms of wound healing, and its effectiveness in treating acute and chronic wounds. Literature searches with no publication date restrictions were conducted using the Cochrane Library, Medline, Web of Science, Google Scholar and PubMed databases, and 30 full-text articles met the inclusion criteria. In vitro and in vivo experiments investigating the effect of ES on the general mechanisms of healing demonstrated increased epithelialization, fibroblast migration, and vascularity around wounds. Six in vitro studies demonstrated bactericidal effects upon exposure to alternating and pulsed current. Twelve randomized controlled trials (RCTs) investigated the effect of pulsed current on chronic wound healing. All reviewed RCTs demonstrated a larger reduction in wound size and increased healing rate when compared to control groups. In conclusion, ES therapy can contribute to improved chronic wound healing and potentially reduce the financial burden associated with wound management. However, the variations in the wound characteristics, patient demographics, and ES parameters used across studies present opportunities for systematic RCT studies in the future.

In situ forming hydrogels are a class of biomaterials that can fulfil a variety of important biomedically relevant functions and hold promise for the emerging field of patient-specific treatments (e.g., cell therapy, drug delivery). Here we report the results of our investigations on the generation of in situ forming hydrogels with potential for wound healing applications (e.g., complex blast injuries). The combination of polysaccharides that were oxidized to display aldehydes, amine displaying chitosan and nanostructured ZnO yields in situ forming bionanocomposite hydrogels. The physicochemical properties of the components, their cytotoxicity towards HaCat cells and the in vitro release of zinc ions on synthetic skin were studied. The in situ gel formation process was complete within minutes, the components were non-toxic towards HaCat cells at functional levels, Zn2+ was released from the gels, and such materials may facilitate wound healing.

Studying cells in a three‐dimensional (3D) environment has great potential in understanding cell behaviours such as morphology, proliferation, differentiation, and migration. Microengineered 3D cell scaffolds with precise defined geometries have offered a new approach to study cell behaviour and its interactions with scaffolds. The use of Raman spectroscopy to characterise biomolecules is a rapidly expanding area and has been implemented in numerous fields including pharmacology, microbiology, toxicology, and single‐cell studies. However, one area where it remains unexploited despite the vast potential of the technique is in the investigation of 3D cell scaffolds. A combination of Raman microscopy and chemometric approaches have employed to investigate the structure and biochemistry of nanofabricated scaffolds and a cell–scaffold complex. The 3D Raman mapping combined with the use of nanofabricated 3D scaffolds offers a unique opportunity to assess the influence of scaffold architecture on cell body and cell nuclei morphology and biochemistry. For the first time, we have cultured a human epithelial colorectal adenocarcinoma cell line on OrmoComp scaffolds and determined the structure and biochemistry of nanofabricated scaffolds and a cell–scaffold complex with the use of Raman microscopy combined with appropriate data analysis protocols. The results demonstrate the potential of 3D Raman mapping for identifying biochemical and physical variation within single cells as they grow and adhere to 3D scaffolds.

The endocannabinoid system has previously been shown to play a role in the permeability and inflammatory response of the human gut. The goal of our study was to determine the effects of endogenous anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) on the permeability and inflammatory response of intestinal epithelium under normal, inflammatory, and hypoxic conditions. Human intestinal mucosa was modeled using Caco-2 cells. Human tissue was collected from planned colorectal resections. Accumulation of AEA and 2-AG was achieved by inhibiting their metabolizing enzymes URB597 (a fatty acid amide hydrolase inhibitor) and JZL184 (a monoacylglycerol lipase inhibitor). Inflammation and ischemia were simulated with TNF-α and IFN-γ and oxygen deprivation. Permeability changes were measured by transepithelial electrical resistance. The role of the CB1 receptor was explored using CB1-knockdown (CB1Kd) intestinal epithelial cells. Endocannabinoid levels were measured using liquid chromatography-mass spectrometry. Cytokine secretion was measured using multiplex and ELISA. URB597 and JZL184 caused a concentration-dependent increase in permeability via CB1 (P < 0.0001) and decreased cytokine production. Basolateral application of JZL184 decreased permeability via CB1 (P < 0.0001). URB597 and JZL184 increased the enhanced (worsened) permeability caused by inflammation and hypoxia (P < 0.0001 and P < 0.05). CB1Kd cells showed reduced permeability response to inflammation (P < 0.01) but not hypoxia. 2-AG levels were increased in response to inflammation and hypoxia in Caco-2 cells. In human mucosal tissue, inflammation increased the secretion of granulocyte macrophage-colony stimulating factor, IL-12, -13, and -15, which was prevented with ex vivo treatment with URB597 and JZL184, and was inhibited by a CB1 antagonist. The results of this study show that endogenous AEA and 2-AG production and CB1 activation play a key modulatory roles in normal intestinal mucosa permeability and in inflammatory and hypoxic conditions.-Karwad, M. A., Couch, D. G., Theophilidou, E., Sarmad, S., Barrett, D. A., Larvin, M., Wright, K. L., Lund, J. N., O'Sullivan, S. E. The role of CB1 in intestinal permeability and inflammation.

The anti-cancer effect of the plant-derived cannabinoid, cannabidiol, has been widely demonstrated both in vivo and in vitro. However, this body of preclinical work has not been translated into clinical use. Key issues around this failure can be related to narrow dose effects, the cell model used and incomplete efficacy. A model of acute lymphoblastic disease, the Jurkat T cell line, has been used extensively to study the cannabinoid system in the immune system and cannabinoid-induced apoptosis. Using these cells, this study sought to investigate the outcome of those remaining viable cells post-treatment with cannabidiol, both in terms of cell size and tracking any subsequent recovery. The phosphorylation status of the mammalian Target of Rapamycin (mTOR) signaling pathway and the downstream target ribosomal protein S6, were measured. The ability of cannabidiol to exert its effect on cell viability was also evaluated in physiological oxygen conditions. Cannabidiol reduced cell viability incompletely, and slowed the cell cycle with fewer cells in the G2/M phase of the cell cycle. Cannabidiol reduced phosphorylation of mTOR, PKB and S6 pathways related to survival and cell size. The remaining population of viable cells that were cultured in nutrient rich conditions post-treatment were able to proliferate, but did not recover to control cell numbers. However, the proportion of viable cells that were gated as small, increased in response to cannabidiol and normally sized cells decreased. This proportion of small cells persisted in the recovery period and did not return to basal levels. Finally, cells grown in 12% oxygen (physiological normoxia) were more resistant to cannabidiol. In conclusion, these results indicate that cannabidiol causes a reduction in cell size, which persists post-treatment. However, resistance to cannabidiol under physiological normoxia for these cells would imply that cannabidiol may not be useful in the clinic as an anti-leukemic agent.

As health care leaders, we often pull staff together to review a process or work on a variety of projects. Think back to the last project you asked staff members to work on. Were they working as a group or a team? Words shape everything: our perception, perspective, the worth of the collective group and the product it produces. The literature uses the terms group and team interchangeably just as many leaders do. Until we define a word, it can have a variety of meanings. The fundamental factors that distinguish between groups and teams are very different, and the distinction between the two is very important. Learning the difference between a group and a team will afford you, as a leader, success in relationships with your staff, project sustainment, and staff members that will naturally rise to leadership roles. All teams are groups; however, not all groups are teams. The purpose of this article is to define the term team and identify strategies nurse leaders can use to effectively develop, analyze, and support high-functioning, collaborative teams.

Cannabinoids modulate intestinal permeability through cannabinoid receptor 1 (CB1). The endocannabinoid-like compounds oleoylethanolamine (OEA) and palmitoylethanolamine (PEA) play an important role in digestive regulation, and we hypothesized they would also modulate intestinal permeability. Transepithelial electrical resistance (TEER) was measured in human Caco-2 cells to assess permeability after application of OEA and PEA and relevant antagonists. Cells treated with OEA and PEA were stained for cytoskeletal F-actin changes and lysed for immunoassay. OEA and PEA were measured by liquid chromatography-tandem mass spectrometry. OEA (applied apically, logEC(50) -5.4) and PEA (basolaterally, logEC(50) -4.9; apically logEC(50) -5.3) increased Caco-2 resistance by 20-30% via transient receptor potential vanilloid (TRPV)-1 and peroxisome proliferator-activated receptor (PPAR)-. Preventing their degradation (by inhibiting fatty acid amide hydrolase) enhanced the effects of OEA and PEA. OEA and PEA induced cytoskeletal changes and activated focal adhesion kinase and ERKs 1/2, and decreased Src kinases and aquaporins 3 and 4. In Caco-2 cells treated with IFN and TNF, OEA (via TRPV1) and PEA (via PPAR) prevented or reversed the cytokine-induced increased permeability compared to vehicle (0.1% ethanol). PEA (basolateral) also reversed increased permeability when added 48 or 72 h after cytokines (P < 0.001, via PPAR). Cellular and secreted levels of OEA and PEA (P < 0.001-0.001) were increased in response to inflammatory mediators. OEA and PEA have endogenous roles and potential therapeutic applications in conditions of intestinal hyperpermeability and inflammation.Karwad, M. A., Macpherson, T., Wang, B., Theophilidou, E., Sarmad, S., Barrett, D. A., Larvin, M., Wright, K. L., Lund, J. N., O'Sullivan, S. E. Oleoylethanolamine and palmitoylethanolamine modulate intestinal permeability in vitrovia TRPV1 and PPAR alpha.

One of the most exciting developments in Raman spectroscopy in the last decade has been its application to cells and tissues for diagnostic and pharmaceutical applications, and in particular its use in the analysis of cellular dynamics. Raman spectroscopy is rapidly advancing as a cell imaging method that overcomes many of the limitations of current techniques and is earning its place as a routine tool in cell biology. In this review we focus on important developments in Raman spectroscopy that have evolved into the exciting technique of live-cell Raman microscopy and highlight some of the most recent and significant applications to cell biology.

Autophagy is a catabolic process involved in homeostatic and regulated cellular protein recycling and degradation via the lysosomal degradation pathway. Emerging data associate impaired autophagy, increased activity in the endocannabinoid system, and upregulation of suppressor of cytokine signaling-3 (SOCS3) protein expression during intestinal inflammation. We have investigated whether these three processes are linked. By assessing the impact of the phytocannabinoid cannabidiol (CBD), the synthetic cannabinoid arachidonyl-2'-chloroethylamide (ACEA), and the endocannabinoid N-arachidonoylethanolamine (AEA) on autophagosome formation, we explored whether these actions were responsible for cyclic SOCS3 protein levels. Our findings show that all three cannabinoids induce autophagy in a dose-dependent manner in fully differentiated Caco-2 cells, a model of mature intestinal epithelium. ACEA and AEA induced canonical autophagy, which was cannabinoid type 1 receptor-mediated. In contrast, CBD was able to bypass the cannabinoid type 1 receptor and the canonical pathway to induce autophagy, albeit to a lesser extent. Functionally, all three cannabinoids reduced SOCS3 protein expression, which was reversed by blocking early and late autophagy. In conclusion, the regulatory protein SOCS3 is regulated by autophagy, and cannabinoids play a role in this process, which could be important when therapeutic applications for the cannabinoids in inflammatory conditions are considered.