The combination of allantoin, bisabolol, D-panthenol and dipotassium glycyrrhizinate mitigates UVB-induced PGE2 synthesis by keratinocytes.

OBJECTIVE: Erythema, characterized by the redness of the skin, is a common skin reaction triggered by various endogenous and exogenous factors. This response is often a result of the activation of underlying inflammatory mechanisms within the skin. The objective of this study is to investigate the potential benefits of applying a combination of skincare ingredients, namely allantoin, bisabolol, D-panthenol and dipotassium glycyrrhizinate (AB5D), in the modulation of inflammatory factors associated with erythema. Additionally, the study aims to elucidate the mechanisms by which these ingredients exert their combined actions to alleviate erythema-associated inflammation. METHODS: Human epidermal keratinocytes were exposed to UVB and subsequently treated with AB5D. Transcriptomics profiling was performed to analyse the dose-response effect of AB5D treatment on keratinocytes. The quantitation of inflammatory mediators, including PGE2 , IL-1α, IL-6, IL-8, IL-1RA and TNFα, was performed on cultured media. Additionally, the oxygen radical absorbance capacity (ORAC) assay was carried out to evaluate the total antioxidant capacity of both individual ingredients and the AB5D combination. To assess the in-vitro antioxidant effects of AB5D against UVB-induced oxidative stress in hTERT keratinocytes, real-time quantitation of mitochondrial superoxide was measured through live-cell imaging. RESULTS: The application of AB5D to UVB-exposed keratinocytes downregulated gene sets associated with inflammatory responses, highlighting the anti-inflammatory properties of AB5D. Specifically, AB5D effectively reduced the production of PGE2 , leading to the downregulation of inflammatory cytokines. Moreover, our findings indicate that AB5D exhibits antioxidative capabilities, functioning as both an antioxidant agent and a regulator of antioxidant enzyme expression to counteract the detrimental effects of cellular oxidative stress. CONCLUSION: We demonstrated that AB5D can reduce UVB-induced PGE2 , IL-1α, IL-6, IL-8, IL-1RA and TNFα as well as mitochondrial superoxide. These findings suggest that AB5D may alleviate erythema by modulating inflammation via PGE2 and through antioxidation mechanisms.

L'érythème, caractérisé par une rougeur sur la peau, est une réaction cutanée fréquente déclenchée par divers facteurs endogènes et exogènes. Il s'agit d'une réponse qui résulte souvent de l'activation des mécanismes inflammatoires sous-jacents dans la peau. OBJECTIF: cette étude vise à étudier les bénéfices potentiels de l'application d'une association d'ingrédients de soins cutanés, à savoir l'allantoïne, le bisabolol, le D-panthénol et le glycyrrhizinate dipotassique (AB5D) dans la modulation des facteurs inflammatoires associés à l'érythème. En outre, l'étude vise à élucider les mécanismes par lesquels ces ingrédients exercent leurs actions combinées pour soulager l'inflammation associée à l'érythème. MÉTHODES: les kératinocytes épidermiques humains ont été exposés aux UVB et traités par la suite par AB5D. Un profilage transcriptomique a été effectué pour analyser l'effet dose-réponse du traitement par AB5D sur les kératinocytes. La quantification des médiateurs inflammatoires, y compris PGE2, IL-1α, IL-6, IL-8, IL-1RA et TNFα, a été effectuée sur des milieux de culture. En outre, le dosage de la capacité d'absorption des radicaux oxygénés (Oxygen Radical Absorbance Capacity, ORAC) a été effectué pour évaluer la capacité antioxydante totale des deux ingrédients individuels et de l'association AB5D. Pour évaluer les effets antioxydants in vitro de l'AB5D contre le stress oxydatif induit par les UVB dans les kératinocytes hTERT, on a mesuré la quantification en temps réel du superoxyde mitochondrial par des tests d'imagerie des cellules vivantes. RÉSULTATS: l'application de l'AB5D aux ensembles de gènes régulés à la baisse exposés aux kératinocytes UVB associés à des réponses inflammatoires, a mis en évidence les propriétés anti-inflammatoires de l'AB5D. Plus précisément, l'AB5D a efficacement réduit la production de PGE2, entraînant une régulation négative des cytokines inflammatoires. En outre, nos résultats indiquent que l'AB5D présente des capacités antioxydantes. Il fonctionne à la fois comme un agent antioxydant et comme un régulateur de l'expression enzymatique antioxydante pour contrer les effets néfastes du stress oxydatif cellulaire. CONCLUSION: nous avons montré que l'AB5D pouvait réduire la PGE2 induite par les UVB, l'IL-1α, l'IL-6, IL-8, IL-1RA et le TNFα, ainsi que le superoxyde mitochondrial. Ces résultats suggèrent que l'AB5D pourrait soulager l'érythème en modulant l'inflammation via la PGE2 et via des mécanismes d'antioxydation.

Dental trauma in endoscopy: A systematic review and experience of a tertiary endoscopy centre.

BACKGROUND: Dental injury is the leading cause of litigation in anaesthesia but an underrecognized preventable complication of endoscopy. AIM: To determine frequency and effects of dental injury in endoscopy, we present findings from an audit of outpatient endoscopy procedures conducted at a tertiary university hospital and a systematic review of literature. METHODS: Retrospective review of 11265 outpatient upper endoscopy procedures over the period of 1 June 2019 to 31 May 2021 identified dental related complications in 0.284% of procedures. Review of literature identified a similar rate of 0.33%. RESULTS: Pre-existing dental pathology or the presence of prostheses makes damage more likely but sound teeth may be affected. Pre-endoscopic history and tooth examination are key for risk stratification and may be conducted succinctly with limited time outlay. Tooth retrieval should be prioritized in the event of dental injury to minimize aspiration and be followed by prompt dental consultation for specific management. CONCLUSION: Dental complications occur in approximately 1 in 300 of upper endoscopy cases. These are easily preventable by pre-endoscopy screening. Protocols to mitigate dental injury are also suggested.

Ectopic adrenocorticotrophic hormone syndrome secondary to treatment-related neuroendocrine differentiation of metastatic castrate-resistant prostate cancer.

Summary: A 64-year-old man with progressive metastatic castrate-resistant prostate adenocarcinoma presented with recurrent fluid overload, severe hypokalaemia with metabolic alkalosis and loss of glycaemic control. Clinical features were facial plethora, skin bruising and proximal myopathy. Plasma adrenocorticotrophic hormone (ACTH), serum cortisol and 24-h urinary cortisol levels were elevated. Low-dose dexamethasone failed to suppress cortisol. Pituitary MRI was normal and 68Gallium-DOTATATE PET-CT scan showed only features of metastatic prostate cancer. He was diagnosed with ectopic ACTH syndrome secondary to treatment-related neuroendocrine prostate cancer differentiation. Medical management was limited by clinical deterioration, accessibility of medications and cancer progression. Ketoconazole and cabergoline were utilised, but cortisol remained uncontrolled. He succumbed 5 months following diagnosis. Treatment-related neuroendocrine differentiation of prostate adenocarcinoma is a rare cause of ectopic ACTH syndrome. Learning points: Neuroendocrine differentiation following prostate adenocarcinoma treatment with androgen deprivation has been described. Ectopic adrenocorticotrophic hormone (ACTH) syndrome should be considered where patients with metastatic prostate cancer develop acute electrolyte disturbance or fluid overload. Ketoconazole interferes with adrenal and gonadal steroidogenesis and can be used in ectopic ACTH syndrome, but the impact may be insufficient. Inhibition of gonadal steroidogenesis is favourable in prostate cancer. More data are required to evaluate the use of cabergoline in ectopic ACTH syndrome. Ectopic ACTH syndrome requires prompt management and is challenging in the face of metastatic cancer.

Anterior Segment Optical Coherence Tomography Angiography Assessment of Corneal Vascularisation After Combined Fine-Needle Diathermy with Subconjunctival Ranibizumab: A Pilot Study.

INTRODUCTION: To describe anterior segment optical coherence tomography angiography (AS-OCTA) imaging to monitor corneal vascularisation (CoNV) and scar reduction after combined fine-needle diathermy (FND) with subconjunctival ranibizumab. METHODS: Prospective clinical study of six eyes from six subjects with corneal scar and CoNV which underwent combined FND with subconjunctival ranibizumab. All eyes were imaged using slit-lamp photography (SLP) and AS-OCTA (Optovue, Inc., Fremont, CA, wavelength: 840 nm) before and after the operation, with two independent masked assessors analysing all images. Main outcome measures were changes in median corneal scar area and vessel density (AS-OCTA) comparing pre- and postoperative imaging up to month 3 and 6. RESULTS: The mean age of the subjects was 60 ± 23 years, with three males and three females. CoNV and corneal scarring involving the visual axis were present in all eyes, secondary to previous infective keratitis (n = 3), severe blepharokeratoconjunctivitis (n = 2), or chemical injury (n = 1). Follow-up time frame ranged from 2 to 6 months postoperation. There was a reduction in median corneal scar area from 30.2 mm2 (IQR 18.7-38.5) before surgery to 14.8 mm2 (IQR 7.1-19.6) after surgery, with a median reduction of 37.1% (IQR = - 3.1-86.9, p = 0.046). There was also a reduction in median cornea vessel density (AS-OCTA) from 20.8% (IQR 16.1-20.8) before surgery to 17.6% (IQR 14.0-17.6) after surgery, with a median reduction of 15.1% (IQR 13.2-15.1, p < 0.001). CONCLUSIONS: Combined imaging of SLP and AS-OCTA is useful for monitoring treatment response of corneal scarring and CoNV after combined FND with subconjunctival Ranibizumab.

Microarray immobilization of biomolecules using a fast trans-cyclooctene (TCO)-tetrazine reaction.

By anchoring 1,2,4,5-tetrazine-containing biomolecules onto trans-cyclooctene (TCO)-functionalized slides, a site-specific microarray immobilization approach is described in this study. Compared with existing immobilization methods, our approach offers several distinctive features, including fast kinetics and high chemoselectivity.

"Minimalist" cyclopropene-containing photo-cross-linkers suitable for live-cell imaging and affinity-based protein labeling.

Target identification of bioactive compounds within the native cellular environment is important in biomedical research and drug discovery, but it has traditionally been carried out in vitro. Information about how such molecules interact with their endogenous targets (on and off) is currently highly limited. An ideal strategy would be one that recapitulates protein-small molecule interactions in situ (e.g., in living cells) and at the same time enables enrichment of these complexes for subsequent proteome-wide target identification. Similarly, small molecule-based imaging approaches are becoming increasingly available for in situ monitoring of a variety of proteins including enzymes. Chemical proteomic strategies for simultaneous bioimaging and target identification of noncovalent bioactive compounds in live mammalian cells, however, are currently not available. This is due to a lack of photoaffinity labels that are minimally modified from their parental compounds, yet chemically tractable using copper-free bioorthogonal chemistry. We have herein developed novel minimalist linkers containing both an alkyl diazirine and a cyclopropene. We have shown chemical probes (e.g., BD-2) made from such linkers could be used for simultaneous in situ imaging and covalent labeling of endogenous BRD-4 (an important epigenetic protein) via a rapid, copper-free, tetrazine-cyclopropene ligation reaction (k2 > 5 M(-1) s(-1)). The key features of our cyclopropenes, with their unique C-1 linkage to BRD-4-targeting moiety, are their tunable reactivity and solubility, relative stability, and synthetic accessibility. BD-2, which is a linker-modified analogue of (+)-JQ1 (a recently discovered nanomolar protein-protein-interaction inhibitor of BRD-4), was subsequently used in a cell-based proteome profiling experiment for large-scale identification of potential off-targets of (+)-JQ1. Several newly identified targets were subsequently confirmed by preliminary validation experiments.