Journal of applied biomedicine最新文献

Background: Ginsenoside Rb2 is beneficial in cardiovascular disease treatment, yet its role in heart failure (HF) is obscure. This study aimed to investigate the effect and mechanism of ginsenoside Rb2 on HF.

Methods: The left anterior descending branch-ligated HF rat model and oxygen-glucose deprivation/reoxygenation (OGD/R) H9c2 cell model were constructed. Ginsenoside Rb2 were applied for intervention. Heart function indexes, miR-216a-5p expression, autophagy, oxidative stress, apoptosis, cell morphology, and proliferation were detected to explore the effect of ginsenoside Rb2 on HF. Overexpression of miR-216a-5p was employed to explore the specific mechanism of ginsenoside Rb2 on HF.

Results: Ginsenoside Rb2 improved the heart function of HF rats, including the reduction of heart rate, LVEDP, and heart weight/body weight ratio, and the increase of LVSP, +dP/dtmax, -dP/dtmax, LVEF, and LVFS. It also down-regulated miR-216a-5p expression and enhanced OGD/R-induced cardiomyocyte viability. Ginsenoside Rb2 up-regulated Bcl2, LC3B II/I, and Beclin1, and down-regulated Bax, Caspase-3, and p62 in the myocardium of HF rats and OGD/R-induced H9c2 cells. Moreover, ginsenoside Rb2 increased the levels of SOD and CAT, but decreased the levels of MDA and ROS in the myocardium of HF rats and OGD/R-induced H9c2 cells. However, overexpression of miR-216a-5p promoted the apoptosis and oxidative stress of cardiomyocytes and inhibited autophagy, thus reversing the therapeutic effect of ginsenoside Rb2 on HF in vivo and in vitro.

Conclusion: Ginsenoside Rb2 demonstrated potential as a therapeutic intervention for HF by enhancing autophagy and reducing apoptosis and oxidative stress through miR-216a-5p downregulation. Further research could explore its application in clinical trials and investigate the complex mechanism networks underlying its effects.

Although many efforts have been made to improve management strategies and diagnostic methods in the past several decades, the prevention of anastomotic complications, such as anastomotic leaks and strictures, remain a major clinical challenge. Therefore, new molecular pathways need to be identified that regulate anastomotic healing, and to design new treatments for patients after anastomosis to reduce the occurrence of complications. Rabbits were treated with a MST1/2 inhibitor XMU-XP-1, a Chinese medicine formula Shenhuang plaster (SHP) or a control vehicle immediately after surgery. The anastomotic burst pressure, collagen deposition, and hydroxyproline concentration were evaluated at 3 and 7 days after the surgery, and qRT-PCR and western-blot analyses were used to characterize mRNA and protein expression levels. Both XMU-XP-1 and SHP significantly increased anastomotic burst pressure, collagen deposition, and the concentration of hydroxyproline in intestinal anastomotic tissue at postoperative day 7 (POD 7). Importantly, SHP could induce TGF-β1 expression, which activated its downstream target Smad-2 to activate the TGF-β1 signaling pathway. Moreover, SHP reduced the phosphorylation level of YAP and increased its active form, and treatment with verteporfin, a YAP-TEAD complex inhibitor, significantly suppressed the effects induced by SHP during anastomotic tissue healing. This study demonstrated that activation of the Hippo-YAP pathway enhances anastomotic healing, and that SHP enhances both the TGF-β1/Smad and YAP signaling pathways to promote rabbit anastomotic healing after surgery. These results suggest that SHP could be used to treat patients who underwent anastomosis to prevent the occurrence of anastomotic complications.

Introduction: False aneurysms in the thoracic aorta are dangerous complications that can occur after cardiac surgery. They often result in high mortality rates. These aneurysms are caused by damage to all layers of the aortic wall. This study aimed to pinpoint the area of the experimental specimen (native vessel, anastomosis, or prosthetic graft) with the greatest deformation, to determine whether a false aneurysm is likely to develop in the anastomotic portion.

Methods: We conducted the inflation-extension test by performing eight cycles ranging from 0 to 20. The pressure sampling frequency was 100 Hz, and each cycle lasted approximately 34 seconds, resulting in a loading frequency of 0.03 Hz. During the experiment, each camera captured 3,000 frames. Based on the data collected, we evaluated and compared the loading stages of cycle 1 and cycle 8.

Results and discussion: During loading, the native vessel experienced a dominant deformation of approximately 7% in the circumferential direction. The prosthetic graft, which had a longitudinal construction, deformed by approximately 8% in the axial direction. The prosthetic graft, on the other hand, only experienced a deformation of up to 1.5% in the circumferential direction, which was about 5 times smaller than the deformation of the native vessel. The anastomosis area was very stiff and showed minimal deformation. Additionally, there was little difference in the mechanical response between the first C1 and the eighth C8 cycle.

Conclusion: Based on the available evidence, it can be inferred that aortic false aneurysms are more likely to form just behind the suture lines in the native aorta, which is more elastic compared to stiff sections of anastomosis and prosthetic graft. Numerous pulsations of the native vessel will likely cause the impairment of the aorta at the margin of the anastomosis. This will lead to disruption of the aortic wall and false aneurysm formation in the native vessel near the area of anastomosis.

Spisulosine (1-deoxysphinganine) is a sphingoid amino alcohol isolated from the sea clams that showed potent antiproliferative activity against a broad spectrum of solid tumors but failed in clinical trials due to neurotoxicity. However, its structural similarity to other bioactive sphingoids, interesting mode of action, and appreciable potency against cancer cells make it a suitable lead for future anticancer drug development. The present study was conducted to elucidate mechanisms of the antiproliferative/cytotoxic effects of newly synthesized spisulosine analog homospisulosine (KP7). The evaluation was performed on cervical carcinoma cells, representing an in vitro model of one of the most common cancer types and a significant worldwide cause of women's cancer mortality. Treatment with homospisulosine (2.0 μM) for 24, 48, and 72 h significantly inhibited the growth of HeLa cells in vitro and induced apoptosis detectable by DNA fragmentation, externalization of phosphatidylserine, dissipation of mitochondrial membrane potential, activation of caspase-3 and cleavage of PARP. In addition, treating HeLa cells with spisulosine increased p27 and Bcl-2 on protein levels and phosphorylation of Bcl-2 on Ser70 residue. These results support the potential for spisulosine analogs represented here by homospisulosine for future therapeutic development.

Introduction: This study aimed to identify the phytochemical constituents that could target gastric cancer in Kangai injection using a network pharmacology-based approach.

Methods: Protein-protein interactions (PPI), Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted utilizing String and OmicShare tools. In the in vitro experiments, the related mRNA and protein levels were assessed via real-time quantitative polymerase chain reaction and Western blotting, respectively. Cell proliferation was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay.

Results: Kangai injection comprises several compounds, which target multiple substrates and pathways related to gastric cancer. The PPI and Gene Ontology analyses revealed that tumor necrosis factor (TNF) was a hub gene. KEGG pathway enrichment analysis indicated that the the TNF pathway was significantly enriched. Kangai injection decreased the mRNA levels of TNFR2, TRAF2, PI3K, AKT, and IκBα and inhibited the phosphorylation of PI3K, AKT, and IκBα phosphorylations. Kangai injection inhibited cell proliferation, while TNFR2 overexpression or treatment with the PI3K activator 740 Y-P partially restored it.

Conclusion: Kangai injection operates through multiple targets and pathways in gastric cancer, with the TNFR2/PI3K/AKT/NF-κB pathway playing a crucial role in its mechanism against gastric cancer.

Purpose: This study investigated EEG alpha rhythm spectral power in children with Specific Language Impairment (SLI) and compared it to typically developing children to better understand the electrophysiological characteristics of this disorder. Specifically, we explored resting-state EEG, because there are studies that point to it being linked to speech and language development.

Methods: EEG recordings of 30 children diagnosed with specific language impairment and 30 typically developing children, aged 4.0-6.11 years, were carried out under eyes closed and eyes open conditions. Differences in alpha rhythm spectral power in relation to brain topography and experimental conditions were calculated.

Results: In the eyes closed condition, alpha rhythm spectral power was statistically significantly lower in children with specific language impairment in the left temporal (T5) and occipital electrodes (O1, O2) than in typically developing children. In the eyes open condition, children with SLI showed significantly lower alpha rhythm spectral power in the left temporal (T3, T5), parietal (P3, Pz), and occipital electrodes (O1, O2). There were no statistically significant differences between the groups in relation to the relative change (the difference between average alpha rhythm spectral power during eyes closed condition and average alpha rhythm spectral power during eyes open condition divided by average alpha rhythm spectral power during eyes closed condition) in the alpha rhythm spectral power between the conditions.

Conclusion: Lower alpha rhythm spectral power in the left temporal, left, midline parietal, and occipital brain regions could be a valuable electrophysiological marker in children with SLI. Further investigation is needed to examine the connection between EEG alpha spectral power and general processing and memory deficits in patients with SLI.

Myocardial hypertrophy may lead to heart failure and sudden death. As traditional Chinese medicine, Guanxinning tablets (GXN) have significant pharmacological effects in the prevention and treatment of cardiovascular diseases. However, the anti-cardiac hypertrophy efficacy of GXN and its mechanism of action are still unclear. Therefore, we established a heart failure rat model and isolated primary cardiomyocytes of neonatal rat to observe the protective effect of GXN on heart failure rat model and the intervention effect on myocardial cell hypertrophy, and to explore the possible mechanism of GXN preventing and treating myocardial hypertrophy. The results of in vivo experiments showed that GXN could significantly reduce the degree of cardiac hypertrophy, reduce the size of cardiomyocytes, inhibit the degree of myocardial remodeling and fibrosis, and improve cardiac function in rats with early heart failure. The results of in vitro experiments showed that GXN was safe for primary cardiomyocytes and could improve cardiomyocyte hypertrophy and reduce the apoptosis of cardiomyocytes in pathological state, which may be related to the inhibition of the over-activation of MEK-ERK1/2 signaling pathway. In conclusion, GXN may inhibit cardiac hypertrophy and improve early heart failure by inhibiting the over-activation of MEK-ERK1/2 signaling pathway.