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Pressure therapy has been used for the prevention and treatment of hypertrophic scars for decades. However, the cellular and molecular mechanisms of this treatment modality have not been fully elaborated, leading to long‐lasting controversies regarding its clinical effectiveness. In this current study, we adopted an in vitro 3D culture and compression model to explore the effect of pressure force on fibroblasts, in order to further explain the working mechanism of compression force during pressure treatment. Human dermal fibroblasts were cultured in the 3D culture hydrogel and treated with 1.5 atm of external compression force through a syringe tube device, for 4, 8, and 20 h respectively. RNA‐seq identified 437 differentially regulated genes after an 8‐h compression intervention compared with control cells, among which 256 genes were up‐regulated and 181 genes were down‐regulated. Further q‐PCR analysis confirmed that early growth response 1(EGR1) and c‐fos were down‐regulated after an 8‐h compression intervention. However, the down‐regulation of EGR1 and c‐fos at the mRNA level does not lead to altered protein synthesis through western blot, for both 8 and 20‐h time points after pressure intervention. Genes closely related to the fibrotic function of fibroblasts including type I collagen (COL1), type III collagen (COL3), transforming growth factor β1(TGF‐β1), matrix metallopeptidase 1 (MMP1), matrix metallopeptidase 1 (TIMP1), connective tissue growth factor (CTGF), α smooth muscle actin (α‐SMA), and fibronectin 1 (FN1), were also unaffected after pressure treatment for 8 h. The current study indicated that in our 3D hydrogel culture model, pressure does not directly affect the fibrotic function of dermal fibroblast in vitro. Indirect regulation including reducing oedema, blood perfusion, and tension could be a more possible mechanism of pressure therapy. [ABSTRACT FROM AUTHOR]

Background and Purpose: Inhibition of PDE5 improves synaptic plasticity and memory via enhancing cGMP expression, thus activating the cGMP/cAMP response element binding protein (CREB) signalling pathway. This study investigated the effects of a PDE5 inhibitor on scopolamine-induced cognitive dysfunction, using memory-related behavioural tests and biochemical assays.Experimental Approach: In mice were pretreated with PDE5 inhibitor, amnesia was induced by scopolamine. The learning and memory abilities of mice were tested using the Morris water maze test, the Y-maze test, the passive avoidance test and the novel object recognition test in sequence. Expression of memory-related bio-molecules and oxidative stress parameters in brain tissue were measured using Western blot and spectrophotometry respectively.Key Results: KJH-1002, a novel and potent inhibitor of PDE5 (IC50 0.059 ± 0.04 nmol·L-1 ), was synthesized. In the behavioural tests, it markedly improved the memory performance impaired by scopolamine, indicating a restoration of cognitive function in the mice. Moreover, KJH-1002 increased cGMP levels in the cortex and the scopolamine-reduced expression of phosphorylated CREB, Levels of ERK 1/2, Akt and brain-derived neurotrophic factor in the cortex and hippocampus were restored by KJH-1002 treatment. In addition, KJH-1002 administration increased the activities of SOD, glutathione peroxidase and glutathione reductase, and decreased the level of malondialdehyde.Conclusion and Implications: KJH-1002 restored cognitive function in scopolamine-induced amnesia mice by activating the cGMP/CREB signalling pathway and attenuating oxidative stress. The beneficial effects of KJH-1002 on cognition indicate its potential as a therapeutic candidate for Alzheimer's disease. [ABSTRACT FROM AUTHOR]