Dendrobine modulates autophagy to alleviate ox-LDL-induced oxidative stress and senescence in HUVECs.

Dendrobine has potential advantages in suppressing atherosclerosis (AS). FK506-binding protein 1A (FKBP1A) is implicated in the regulation of autophagy, inflammation, and apoptosis. To reveal the mechanism by which dendrobine inhibits AS by modulating autophagy, oxidative stress, apoptosis, and senescence. An in vitro AS cell model was induced by culturing human umbilical vein endothelial cells (HUVECs) with oxidized low-density lipoprotein (ox-LDL). The cells were treated with dendrobine alone or in combination with short hairpin RNA (shRNA) targeting FKBP1A or together with 3-methyladenine (3MA), an autophagy inhibitor. Inflammatory cytokines levels tumor necrosis factor-α, interleukin-6 (IL-6), and IL-1ß were analyzed and oxidative stress levels were detected by the analysis of reactive oxygen species, malondialdehyde, and superoxide dismutase levels, followed by the analysis of apoptosis levels through terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Cell senescence was evaluated by senescence-associated ß-galactosidase and light chain 3 (LC3) levels were detected by immunofluorescence (IF) staining. The targeting relationship of dendrobine and FKBP1A was predicted by SwissTarget, PyMol, Autodock, and Open Babel software. Dendrobine reduced the levels of proinflammation factors, oxidative stress levels, apoptosis levels, and senescence phenotype in ox-LDL-induced HUVECs. Besides, cell viability has an opposite change. Furthermore, there was an increase in LC3 IF tensity, and LC3-II/I and Beclin1 expressions, and a decrease in p62 expression. However, these effects of dendrobine could be markedly destroyed by shRNA silencing FKBP1A and 3MA. Dendrobine can suppress inflammatory responses, oxidative stress, apoptosis, and senescence via FKBP1A-involved autophagy ox-LDL-treated HUVECs.

Clinical effects of Lingguizhugan decoction in the treatment of hypertension: a systematic review and meta-analysis.

BACKGROUND: Lingguizhugan decoction is commonly used to treat metabolic syndrome; however, its curative effect on hypertension is still unclear. Our study aimed to evaluate the clinical efficacy and safety of Lingguizhugan decoction combined with western medicine in the treatment of hypertension. METHODS: We searched 7 electronic databases for relevant studies and full-text articles involved in the evaluation of clinical effects difference between Lingguizhugan decoction combined with western medicine and western medicine alone. All included articles were quality assessed and data analysis was conducted with Review Manager (5.4). Sensitivity analysis was performed, and the results were visualized by means of forest and funnel plots. Results were expressed as risk ratio (RR) or mean difference (MD), together with their 95% confidence intervals (CIs). RESULTS: In total, 7 studies eventually met our inclusion criteria. The results showed that Lingguizhugan decoction combined with western medicine had a better improvement in decrease systolic blood pressure (SBP) (MD =12.33 mmHg; 95% CI: 3.37 to 21.28; P=0.007) and diastolic blood pressure (DBP) (MD =7.42 mmHg; 95% CI: 1.89 to 12.95; P=0.009) than western medicine alone, it also had a higher effective ratio (RR =1.20; 95% CI: 1.11 to 1.31; P<0.0001) and lower adverse reactions (RR =0.51; 95% CI: 0.30 to 0.86; P=0.01). The results were robust and no obvious publication bias was observed in this study. DISCUSSION: Our research supported that Lingguizhugan decoction combined with western medicine can effectively reduce patients' blood pressure and improve their clinical symptoms. Because of the limitation in the quantity and quality of the included studies, further large sample and multi center follow-up controlled trials should be carried out to validate our conclusions.

Biological evaluation of linalool on the function of blood vessels.

Long­term hypertension leads to alterations in the structure and function of blood vessels, and abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are important factors for these changes. Linalool is a natural compound extracted from plants. The present study aimed to explore the role and underlying mechanism of linalool in the physiological behavior of VSMCs. Angiotensin II (Ang II) was utilized to treat VSMCs, and MTT and western blotting assays were then employed to detect the effect of linalool on the induced proliferation and migration of VSMCs. The target gene of linalool was predicted by the SwissTargetPrediction website, and its expression level in VSMCs was determined using reverse transcription­quantitative PCR and western blotting. Next, the role of the target gene in the physiological behavior of VSMCs treated with linalool was examined, and the signaling pathway was explored. The results revealed that the proliferation and migration of VSMCs treated with Ang II were significantly promoted, and linalool could alleviate these effects in a dose­dependent manner. Cholinergic receptor muscarinic 3 (CHRM3), as a predicted target, was found to be highly expressed in Ang II­induced VSMCs, and CHRM3 overexpression could prevent the inhibitory effect of linalool on cell proliferation and migration. In addition, its overexpression caused an increase in the expression of proteins related to the MAPK signaling pathway. In conclusion, linalool inhibited the proliferation and migration of Ang II­induced VSMCs and blocked the MAPK signaling pathway by downregulating CHRM3.

Comparison of the neuromuscular blocking effects of cisatracurium during isoflurane or propofol anesthesia in dogs.

OBJECTIVE: To compare the neuromuscular blocking effects of cisatracurium during isoflurane versus propofol anesthesia in dogs. STUDY DESIGN: Prospective, randomized study. ANIMALS: A total of 20 healthy, client-owned dogs (16 females, four males) weighing 12.5-22 kg and aged 1-8 years. METHODS: Dogs undergoing elective surgery were randomized in equal numbers to an isoflurane (ISO) or propofol (PPF) group. Other drugs used during anesthesia were equal between groups. Single-twitch (ST) stimulation was used to monitor neuromuscular response. After recording the baseline ST (T0), cumulative doses of cisatracurium (0.05 mg kg-1) were administered intravenously until ST/T0 ≤5%. Effective doses 50 (ED50) and 95 (ED95) of cisatracurium in each group were calculated from group dose-response curves. Recovery of ST (TR) was defined as spontaneous recovery of ST to 80-120% of T0 remaining stable for 2 minutes. The ST after each dose of cisatracurium, duration 25% (time after the last dose until 25% recovery of TR), recovery index (time to recovery from 25% to 75% of TR) and duration to TR (time after the last dose until recovery of TR) were recorded. RESULTS: Incremental doses of cisatracurium, median (range), were 2 (1-3) in ISO and 4 (2-5) in PPF to achieve ≥95% depression of ST/T0 (p < 0.01). ED50 and ED95 were 20 µg kg-1 and 117 µg kg-1 in ISO and 128 µg kg-1 and 167 µg kg-1 in PPF, respectively. The duration 25%, recovery index and duration to TR, median (range), were longer in ISO [22.6 (10.3-24.3), 5.3 (3.0-7.8) and 36.1 (20.1-49.7) minutes, respectively] than in PPF [10.2 (6.8-16.5), 3.0 (2.0-3.8) and 17.7 (14.2-28.7) minutes, respectively] (p < 0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Cisatracurium-induced neuromuscular blockade was significantly enhanced and prolonged by isoflurane compared with propofol.