Selenium Deficiency Promotes Dilatation of the Aorta by Increasing Expression and Activity of Vascular Smooth Muscle Cell Derived Matrix Metalloproteinase-2.

OBJECTIVE: Selenium (Se) is a key part of the body's oxidation defence system. However, it is unclear whether Se affects the development of aortic aneurysm (AA). An animal experiment was conducted to clarify the role of Se in AA development. METHODS: C57BL/6N male mice were fed with a Se deficient (Se-D, < 0.05 mg/kg), Se adequate (Se-A, 0.2 mg/kg), or Se supplemented (Se-S, 1 mg/kg) diet for 8 weeks. Subsequently, an AA murine model (Se-D, n = 11; Se-A, n = 12; Se-S, n = 15) was established using angiotensin II (Ang II, 1 mg/kg/min) for four weeks plus ß-aminopropionitrile (BAPN, 1 mg/mL) for the first two weeks. Saline replaced Ang II, and BAPN was removed during the modelling process for sham mice (Se-A, n = 9). To determine whether Se deficiency promoted aortic dilation via matrix metalloproteinase-2 (MMP-2), the non-specific MMP inhibitor doxycycline (Dox, 100 mg/kg/day) was given to Se-D AA mice (n = 7) for two weeks. RESULTS: The maximum aortic diameter in Se-D AA model mice was significantly increased compared with Se-A AA model mice. MMP-2 expression and activity in the aortic media of Se-D AA model mice was significantly increased compared with Se-A AA model mice. A large number of vascular smooth muscle cells (VSMCs) were found aggregating in the media of the non-dilated aorta of Se-D AA model mice, which was completely inhibited by Dox. The percentage of VSMCs in aortic media of Se-D AA model mice was significantly higher than in Se-A AA model mice. The maximum aortic diameter and occurrence rate of AA in Se-D AA model mice with Dox were significantly reduced compared with Se-D AA model mice. CONCLUSION: Se deficiency promoted dilatation of the aorta in AA model mice by increasing expression and activity of VSMC derived MMP-2, causing abnormal aggregation and proliferation of VSMCs in aortic media.

Quercetin Reduces the Virulence of S. aureus by Targeting ClpP to Protect Mice from MRSA-Induced Lethal Pneumonia.

The dramatic increase of methicillin-resistant Staphylococcus aureus (MRSA) poses a great challenge to the treatment of Staphylococcus aureus (S. aureus) infections. Therefore, there is an urgent need to identify novel anti-infective agents to attack new targets to overcome antibiotic resistance. Casein hydrolase P (ClpP) is a key virulence factor in S. aureus to maintain cellular homeostasis. We screened from flavonoids and finally determined that quercetin could effectively attenuate the virulence of MRSA. The results of the thermal shift assay showed that quercetin could bind to ClpP and reduce the thermal stability of ClpP, and the KD value between quercetin and ClpP was 197 nM as determined by localized surface plasmon resonance. We found that quercetin exhibited a protective role of a mouse model of MRSA-induced lethal infection in a murine model. Based on the above facts, quercetin, as a ClpP inhibitor, could be further developed as a potential candidate for antivirulence agents to combat S. aureus infections. IMPORTANCE The resistance of Staphylococcus aureus (S. aureus) to various antibiotics has increased dramatically, and thus the development of new anti-infective drugs with new targets is urgently needed to combat resistance. Caseinolytic peptidase P (ClpP) is a casein hydrolase that has been shown to regulate a variety of important virulence factors in S. aureus. Here, we found that quercetin, a small-molecule compound from traditional Chinese herbal flavonoids, effectively inhibits ClpP activity. Quercetin attenuates the expression of multiple virulence factors in S. aureus and effectively protects mice from lethal pneumonia caused by MRSA. In conclusion, we determined that quercetin is a ClpP inhibitor and an effective lead compound for the development of a virulence factor-based treatment for S. aureus infection.

Efficacy of "Pinggan Formula" in Controlling Acute Type B Aortic Dissection Perioperative Blood Pressure: A Randomized Controlled Clinical Trial.

OBJECTIVE: To explore a new treatment that can proceed from the whole, control blood pressure smoothly and coordinate the treatment of multiple factors causing blood pressure fluctuations. METHOD: We conducted a single-center, double-blinded, and randomized controlled clinical trial. 48 patients with acute Type B aortic dissection were randomly assigned into two groups: the experimental group, who received pinggan formula treatment, and the control group, who received placebo treatment. The drug was taken orally after meals three times a day. Only when the patients' blood pressure fluctuated, conventional antihypertensive drugs were given to maintain the blood pressure within the target range and the dosage was recorded to convert the DDD value. Meanwhile, the international standardized score was used to evaluate the defecation, sleep, pain, anxiety, and depression of patients in the two groups during the hospitalization. RESULT: Univariate analysis was conducted on variables that might affect the assessment results, and it was found that grouping factors had a significant impact on the outcome variables, that is, after the intervention, the mean value of DDDs used in the perioperative period in the control group was 2.19 (0.38, 4.00). (P=0.0219), defecation score (2.13 (1.59, 2.67); P < 0.0001), sleep score (0.95 (0.40, 1.50); P=0.0014), pain score (1.77 (0.61, 2.93); P=0.0045), depression score (4.04 (2.95, 5.12); and P < 0.0001) were significantly higher than that of the experimental group, and the difference was statistically significant. CONCLUSION: Pinggan formula has a clear therapeutic regulation effect on the overall hemodynamics of acute Stanford type B aortic dissection during the perioperative period and can be recommended as an auxiliary drug for conventional antihypertensive drugs at the current stage.