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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: Myocardial infarction (MI) induces high morbidity all over the world. Patients with MI are more vulnerable to depression, and depression worsens their prognosis. Inflammatory response is the primary pathophysiological mechanism of MI combined with depression. Therefore, MI and depression would benefit from attenuating inflammation. Objectives: To explore the anti-inflammation effect in relieving heart dysfunction and depressive behaviors of mice under MI and chronic stress. Materials and Methods: A total of 40 male C57BL/6J mice were given sham or MI surgery, and the success rate of the surgery was 80%. Hence, 32 mice survived surgery and were distributed as 8 in each group of study. Then, unpredictable chronic mild stress (UCMS) or Anshen Buxin Liuwei pills (ABL pills) group were applied to some MI mice, and the mice were divided into different groups, including sham group, MI group, MI + UCMS group, and MI + UCMS + ABL pills group (n = 8). After a 2-week treatment, the mice underwent the sucrose preference test, and echocardiography before sacrifice. Then, the mice were sacrificed for pathological detection and inflammatory cytokines detection. Results: Compared with mice in the sham group, those mice had lower left ventricular ejection fraction (LVEF) (51.25 ± 9.92 vs. 12.18 ± 8.46, 20.95 ± 16.40, 29.55 ± 13.33%, P < 0.05) and left ventricular fractional shortening (LVFS) (21.12 ± 6.82 vs. 5.57 ± 4.0, 9.89 ± 8.03, 14.0 ± 6.65%, P < 0.05) in the MI, MI + UCMS, and MI + UCMS + ABL pills groups. ABL pills could reverse cardiac dysfunction for the significant elevation of LVEF and LVFS. The hematoxylin and eosin staining presented left ventricular (LV) enlargement, inflammatory cell infiltration, and myocardial fibrosis formation in MI and MI + UCMS mice. While ABL pills reversed the pathological changes induced by ligation of the left anterior descending. The enzyme-linked immunosorbent assay detection showed that MI and MI + UCMS elevated the concentrations of cardiac tumor necrosis factor-α (TNF-α) and tumor necrosis factor receptor 1 (TNFR1), which were reduced by ABL pills. ABL pills significantly reversed the depressive behaviors of mice with MI + UCMS (82.97 ± 3.04 vs. 76.07 ± 7.84%, P < 0.05). MI + UCMS group had a higher level of cortex TNFR1 than sham and MI, while ABL pills reversed the elevation (P > 0.05). Conclusions: Anti-inflammation treatment effectively improves cardiac function and depressive behaviors via inhibiting TNF-α/TNFR1. [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]

Background: Previously, Huangqi decoction (HQD) has been found to have a potential therapeutic effect on DMN-induced liver cirrhosis. Here, the mechanisms of HQD action against liver fibrosis were investigated in relation to hepatocyte apoptosis and hepatic inflammation regulation. Methods: Liver fibrosis was induced by DMN administration for 2 or 4 weeks. Hepatocyte apoptosis and of Kupffer cells (KC) and hepatic stellate cells (HSC) interaction were investigated using confocal microscopy. The principle cytokines, fibrogenic proteins and apoptotic factors were investigated using western blot analysis. Results: Compared with the DMN-water group, HQD showed decreased hepatocyte apoptosis and reduced expression of apoptotic effectors, cleaved-caspase-3, and fibrotic factors, such as smooth muscle α-actin (α-SMA), transforming growth factor beta-1 (TGF-β1). However, the KC marker CD68 increased significantly in DMN-HQD liver. Confocal microscopy demonstrated widespread adhesion of KCs to HSCs in DMN-water and DMN-HQD rats liver. Conclusions: HQD exhibited positive protective effects against liver fibrosis; its mechanism of action was associated with protection from hepatocyte apoptosis and the promotion of CD68 expression in the devolopment of liver fibrosis to cirrhosis development. [ABSTRACT FROM AUTHOR]