European journal of pharmacology
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Organoids are self-organizing, multicellular structures that contain multiple cell types, represent organ structure and function, and can be used to model organ development, maintenance and repair ex vivo. Organoids, derived from embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) or adult stem cells, are cultured in extracellular matrix (ECM). ⋯ In addition, we will discuss the read out strategies to evaluate organoid phenotype and function. Finally, we will indicate how the choice of both culture parameters and read out strategy should be tailored to specific applications of the organoid culture.
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Casticin, an active compound isolated from Vitex Fructus, has been reported to have anti-inflammatory effects in previous studies. The present study was designed to evaluate the protective effects of casticin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and clarify the underlying mechanisms. ALI was induced by intratracheal instillation of LPS. ⋯ Furthermore, casticin suppressed LPS-induced NF-κB activation, and NLRP3, ASC, and caspase-1 expression. In conclusion, the results suggested that casticin had a protective effect against LPS-induced ALI. Casticin protected against LPS-induced ALI by inhibiting inflammatory cytokines production through the inhibition of NF-κB and NLRP3 signaling pathways.
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Centhaquin has been shown to produce antinociception in the mouse hot plate and tail flick assays through the opioid, the α2A and α2B adrenoceptors. Present study was conducted to determine the effects of centhaquin in a rat model of postoperative pain. Involvement of opioid, and adrenergic receptors was assessed by pretreating rats with antagonists at the opioid (naloxone), α2-(atipamezole) or α2B-(imiloxan) adrenergic receptors. ⋯ This is the first report demonstrating centhaquin antinociception in the rat postoperative pain model. Opioid, α2 adrenergic, and particularly α2B adrenergic receptors are involved in mediating antihyperalgesia while attenuation of nonevoked guarding is mediated by α2B/α2 adrenergic receptors. Centhaquin could be an effective non-sedating alternative in treating postoperative pain in ambulatory surgeries.
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Lacosamide is an anti-epileptic drug that is also used for the treatment of painful diabetic neuropathy acting through voltage-gated sodium channels. The aim of this work was to evaluate the effects of acute application of lacosamide on the electrical activity of corneal cold nerve terminals in lacrimo-deficient guinea pigs. Four weeks after unilateral surgical removal of the main lachrimal gland in guinea pigs, corneas were excised and superfused in vitro at 34°C for extracellular electrophysiological recording of nerve terminal impulse activity of cold thermosensitive nerve terminals. ⋯ Temperature threshold was increased by the addition of lidocaine (P<0.05) but not lacosamide (P>0.05) to the irrigation fluid. In summary, the application of lacosamide results in a significant decrease of the augmented spontaneous activity and responsiveness to cold of corneal sensory nerves from tear-deficient animals. Based on these promising results we speculate that lacosamide might be used to reduce the hyperexcitability of corneal cold receptors caused by prolonged ocular surface dryness due to hyposecretory or evaporative dry eye disease.
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Asthma is a chronic inflammatory heterogeneous disorder initiated by a dysregulated immune response which drives disease development in susceptible individuals. Though T helper 2 (TH2) biased responses are usually linked to eosinophilic asthma, other Th cell subsets induce neutrophilic airway inflammation which provokes the most severe asthmatic phenotypes. A growing evidence highlights the role of T regulatory (Treg) cells in damping abnormal Th responses and thus inhibiting allergy and asthma. ⋯ It also ameliorated goblet cell metaplasia and bronchial fibrosis. Splenocytes flow cytometry revealed increased percentage of CD4(+) CD25(+) FOXP3(+) Treg cells by Adalimumab that was associated with increase in their suppressive activity as shown by elevated BAL fluid IL-10. We conclude that the beneficial effects of Adalimumab in this CD1 neutrophilic model of allergic airway inflammation are attributed to augmentation of Treg cell number and activity.