Sodium valproate inhibited apoptosis in lethally scalded rat cardiomyocytes by regulating hypoxia-inducible factor-1α expression.

This study assessed the inhibitory effect of sodium valproate (VPA) on apoptosis of cardiomyocytes in lethally scalded rats. The model of a 50% total body surface area (TBSA) third-degree full-thickness scald was produced, 48 male SD rats were randomly divided into three groups (n = 16), the sham group and the scald group were given an intraperitoneal injection of 0.25ml of saline, the scald +VPA group was given an intraperitoneal injection of VPA (300 mg/kg) after scalded, Each group was subdivided into two subgroups (n=8) according to the two observation time points of 3h and 6h after scald. Apoptotic cardiomyocytes were observed, and myocardial tissue levels of nitric oxide (NO), cysteine protease-3 (caspase-3) activity, hypoxia-inducible factor-1α (HIF-1α), inducible nitric oxide synthase (iNOS), BCL2/adenovirus E1B interacting protein 3 (BNIP3) and caspase-3 protein were measured. Compared with sham scald group, severe scald elevated CK-MB, cardiomyocyte apoptosis rate, caspase-3 activity and protein levels, NO content, and HIF-1α signalling pathway proteins; whereas VPA decreased CK-MB, cardiomyocyte apoptosis rate and inhibited HIF-1α signalling pathway protein expression. In conclusion, these results suggested that VPA inhibited early cardiomyocyte apoptosis and attenuated myocardial injury in lethally scalded rats, which may be related to the regulation of the HIF-1α signalling pathway.

Aberrant effort-based reward dynamics in anhedonia.

Anhedonia is a transdiagnostic symptom and associated with a spectrum of reward deficits among which the motivational dysfunction is poorly understood. Previous studies have established the abnormal cost-benefit trade-off as a contributor to motivational deficits in anhedonia and its relevant psychiatric diseases. However, it remains elusive how the anhedonic neural dynamics underlying reward processing are modulated by effort expenditure. Using an effort-based monetary incentive delay task, the current event-related potential study examined the neural dynamics underlying the effort-reward interplay in anhedonia using a nonclinical sample who scored high or low on an anhedonia questionnaire. We found that effort prospectively decreased reward effect on the contingent variation negativity and the target-P3 but retrospectively enhanced outcome effect on the feedback-P3 following effort expenditure. Compared to the low-anhedonia group, the high-anhedonia group displayed a diminished effort effect on the target-P3 during effort expenditure and an increased effort-enhancement effect for neutral trials during the feedback-P3 period following effort expenditure. Our findings suggest that anhedonia is associated with an inefficient control and motivation allocation along the efforted-based reward dynamics from effort preparation to effort production.

Effects of Thymosin ß4 on Myocardial Apoptosis in Burned Rats.

The aim of this study was to investigate the effects of thymosin ß4 on myocardial apoptosis following burns. Fifty healthy Sprague Dawley (SD) rats were randomly divided into the normal control group, resuscitation group the low-dose Tß4 (thymosin ß4) group (2g), the medium-dose Tß4 group (6g), and the high-dose Tß4 group (18g). The rats were immersed in 95°C hot water for 18 seconds, and then the model of 30% body surface area (TBSA) III° scald was established. The resuscated rats were injected with lactate Ringer's solution for antishock rehydration, while the Tß4 treatment group was injected with lactate Ringer's solution for antishock rehydration, and the animals were sacrificed 6 h after scald. The degree of histopathological damage was observed by HE (hematoxylin and eosin) staining. Western blot was used to detect STAT1 and STAT3 protein expression levels. Real-time PCR was used to detect mRNA expressions of STAT1 and STAT3. The results showed that the apoptosis rate of the resuscitation group was significantly higher than that of the control group (P < 0.01). Compared with the resuscitation group, the apoptosis rate of thymosin ß4 in the treatment group was significantly reduced (P < 0.01). Compared with the normal control group, the expression of STAT1 protein was increased and the expression of STAT3 protein was decreased in model group rats after ischemia and reperfusion. Compared with the model group, the expression of STAT1 protein decreased and the expression of STAT3 protein increased after ischemia-reperfusion in the thymosin ß4 treatment group. Thymosin ß4 may protect the myocardium by downregulating STAT1 and upregulating STAT3 expression and inhibiting myocardial apoptosis induced by ischemia and reperfusion after severe scald injury.

Effect Evaluation of Platelet-Rich Plasma Combined with Vacuum Sealing Drainage on Serum Inflammatory Factors in Patients with Pressure Ulcer by Intelligent Algorithm-Based CT Image.

This work was to explore the efficacy of intelligent algorithm-based computed tomography (CT) to evaluate platelet-rich plasma (PRP) combined with vacuum sealing drainage (VSD) in the treatment of patients with pressure ulcers. Based on the u-net network structure, an image denoising algorithm based on double residual convolution neural network (Dr-CNN) was proposed to denoise the CT images. A total of 84 patients who were hospitalized in hospital were randomly divided into group A (without any intervention), group B (PRP treatment), group C (VSD treatment), and group D (PRP+VSD treatment). Procalcitonin (PCT) was detected by enzyme-linked immunosorbent assay (ELISA) combined with immunofluorescence method, C-reactive protein (CRP) was detected by rate reflectance turbidimetry (RRT), and interleukin-6 (IL-6) was detected by electrochemiluminescence method. The results showed that after treatment, 44 cases (52.38%) of pressure ulcers patients recovered, 24 cases (28.57%) had no change in stage, and 16 cases (19.04%) developed pressure ulcers. The pain scores of group D at 1 week (3.35 ± 0.56 points) and 2 weeks (2.76 ± 0.55 points) after treatment were significantly lower than those in group C (7.77 ± 0.58 points and 6.34 ± 0.44 points, respectively). The time of complete wound healing in group D (24.5 ± 2.32) was obviously lower in contrast to that in groups A, B, and C (35.54 ± 3.22 days, 30.23 ± 2 days, and 29.34 ± 2.15 days, respectively). In addition, the medical satisfaction of group D (8.74 ± 0.69) was significantly higher than that of groups A, B, and C (4.69 ± 0.85, 5.22 ± 0.31, and 5.18 ± 0.59, respectively). The levels of IL-6 and PCT in group D were lower than those in groups A, B, and C, and the differences were statistically significant (P < 0.01). The average values of peak signal to noise ratio (PSNR) and structural similarity index measure (SSIM) of the Dr-CNN network model were 37.21 ± 1.09 dB and 0.925 ± 0.01, respectively, which were higher than other algorithms. The mean values of root mean square error (MSE) and normalized mean absolute distance (NMAD) of the Dr-CNN network model were 0.022 ± 0.002 and 0.126 ± 0.012, respectively, which were significantly lower than other algorithms (P < 0.05). The experimental results showed that PrP combined with VSD could significantly reduce the inflammatory response of patients with pressure ulcers. PRP combined with VSD could significantly reduce the pain of dressing change for patients. Moreover, the performance model of image denoising algorithm based on double residual convolutional neural network was better than other algorithms.

MicroRNA-185 inhibits the proliferation and migration of HaCaT keratinocytes by targeting peroxisome proliferator-activated receptor ß.

Proliferation and migration of keratinocytes are major processes of skin wound repair after injury. It has been indicated that microRNAs (miRNAs/miRs) are associated with the proliferation and migration of keratinocytes. However, the mechanism by which miR-185 affects these processes in keratinocytes remains unclear. In the present study, the expression level of miR-185 and peroxisome proliferator-activated receptor ß (PPARß) was examined by reverse transcription-quantitative PCR in HaCaT keratinocytes. Cell proliferation was evaluated using Cell Counting Kit-8 and colony formation assays. Western blot analysis was used to detect the levels of cell proliferation, migration and PI3K/AKT signaling pathway-associated proteins. In addition, the migratory capacity of the cells was determined using Transwell assay. The target gene of miR-185 was verified using dual-luciferase reporter assay. The results indicated that overexpression of miR-185 inhibited proliferation, migration and activation of the PI3K/AKT signaling pathway in HaCaT keratinocytes. PPARß was indicated to be a target of miR-185 and its overexpression promoted the proliferation and migration of HaCaT keratinocytes, while its knockdown exhibited the adverse effects. Furthermore, PI3K inhibitor LY294002 inhibited activation of the PI3K/AKT signaling pathway and decreased the proliferation and migration of HaCaT keratinocytes. In addition, overexpressed PPARß reversed the suppressive effects of miR-185 overexpression on proliferation, migration and activation of the PI3K/AKT signaling pathway. In conclusion, the results of the present study demonstrated that miR-185 suppressed activation of the PI3K/AKT signaling pathway via targeting PPARß, thereby regulating proliferation and migration in HaCaT keratinocytes. The present study provided a novel theoretical basis for the use of miR-185 as a target in wound repair.

NEAT1 Knockdown Inhibits Keloid Fibroblast Progression by miR-196b-5p/FGF2 Axis.

BACKGROUND: Keloid is a benign fibroproliferative tumor of the skin caused by abnormal wound healing process after skin injury. Long noncoding RNAs have been reported to be involved in the development of keloid. However, the role and mechanism of nuclear enriched abundant transcript 1 (NEAT1) in keloid are still unknown. METHODS: Quantitative real-time polymerase chain reaction was performed to detect the expression of NEAT1, miR-196b-5p, and fibroblast growth factor 2 (FGF2). Western blot was conducted to measure the levels of collagen I, α-smooth muscle actin, fibronectin, and FGF2. Cell Counting Kit-8 assay and transwell assay were used to evaluate cell viability and migration, respectively. Dual-luciferase reporter assay was conducted to verify the targeting relationship between miR-196b-5p and NEAT1 or FGF2. RESULTS: NEAT1 was increased and miR-196b-5p was decreased in keloid tissues and fibroblasts. NEAT1 knockdown or miR-196b-5p overexpression suppressed cell viability, migration, and extracellular matrix (ECM) component production in keloid fibroblasts. MiR-196 b-5p was a target of NEAT1, and NEAT1 overexpression reversed the effect of miR-196b-5p on keloid fibroblast progression. Moreover, we found that miR-196b-5p directly targeted FGF2. FGF2 knockdown suppressed keloid fibroblast viability, migration, and ECM protein production. FGF2 overexpression abolished the effect of miR-196b-5p overexpression on keloid fibroblast development. CONCLUSIONS: NEAT1 silencing suppressed cell viability, migration, and ECM expression in keloid fibroblasts by regulating miR-196b-5p/FGF2 axis, indicating a promising strategy for keloid treatment.

Loganin attenuates intestinal injury in severely burned rats by regulating the toll-like receptor 4/NF-κB signaling pathway.

Severe burns may lead to intestinal inflammation and oxidative stress, resulting in intestinal barrier damage and gut dysfunction. Loganin, an iridoid glycoside compound, has been isolated from Cornus officinalis Sieb. et Zucc; however, its role in the treatment of burn injury is yet to be fully elucidated. Therefore, the present study examined the effect of loganin administration on burn-induced intestinal inflammation and oxidative stress after severe burns in male Sprague-Dawley rats. Histological injury was assessed by hematoxylin and eosin staining. Furthermore, cytokine expression in intestinal tissues was measured by ELISA and reverse transcription-quantitative PCR. Antioxidative activities were assessed by determining the levels of reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA). Apoptosis was detected by flow cytometry. Apoptosis-related proteins, toll-like receptor 4 (TLR4) protein and NF-κB translocation were examined by western blotting. Immunohistochemical staining was used to observe TLR4 and NF-κB p65 expression in intestinal tissues. The present study suggested that loganin administration significantly reduced burn injury-induced intestinal histological changes, tumor necrosis factor-α, interleukin (IL)-6 and IL-1ß production and oxidative stress, evidenced by decreased ROS levels and MDA content (P<0.05). Furthermore, loganin increased SOD, CAT and GSH-Px levels and intestinal epithelial cell apoptosis. Loganin treatment also significantly inhibited activation of the TLR4/NF-κB signaling pathway in the intestine of severely burned rats (P<0.05). In conclusion, loganin reduced burns-induced intestinal inflammation and oxidative stress, potentially by regulating the TLR4/NF-κB signaling pathway.