The effect of PCSK9 inhibitors on brain stroke prevention: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Although proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to improve cardiovascular outcomes, their effects on brain stroke risk are unclear. The present meta-analysis aimed to evaluate the effects of PCSK9 inhibitors on brain stroke prevention. METHODS AND RESULTS: We searched PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov for research published until December 30, 2020, to find randomized controlled trials (RCTs) of PCSK9 inhibitors for brain stroke prevention. Relative risk (RR) and 95% confidence intervals (CIs) were used to represent the outcomes. Seven RCTs with 57,440 participants, including 29,850 patients treated with PCSK9 inhibitors and 27,590 control participants, were included. PCSK9 inhibitors were associated with significant reductions in total brain stroke risk (RR, 0.77; 95% CI, 0.67-0.88; P < 0.001) and ischemic brain stroke risk (RR, 0.76; 95% CI, 0.66, 0.89; P < 0.001) in comparison with the control group. There was no significant difference in cardiovascular mortality (RR, 0.95; 95% CI, 0.84-1.07; P = 0.382) and the risk of hemorrhagic brain stroke (RR, 1.00; 95% CI, 0.66-1.51; P = 0.999) between patients treated with PCSK9 inhibitors and controls. PCSK9 inhibitors did not significantly increase the incidence of neurocognitive adverse events (RR, 1.02; 95% CI, 0.81-1.29; P = 0.85). Moreover, subgroup analysis showed no difference in cognitive function disorder risks among different PCSK9 inhibitors and treatment times. CONCLUSIONS: PCSK9 inhibitors significantly reduced the risk of total brain stroke and ischemic brain stroke without increasing the risk of brain hemorrhage and neurocognitive impairment.

Surface-enhanced Raman spectroscopic analysis of N6-benzylaminopurine residue quantity in sprouts with gold nanoparticles.

A rapid and quantitative method for the determination of N6-Benzylademine (N6-BA) was established through the application of surface-enhanced Raman spectroscopy (SERS). The Raman peak intensities of N6-BA at 1002 cm-1 positively correlated to N6-BA concentrations in sprout extracts. The R2 reached 0.99, and RSDs calculated below 10% at the concentration range of 0.1 ∼5µg mL-1. The average recoveries were 80.0% ∼ 98.2% for blank samples intentionally contaminated at differing levels of 0.04, 0.4, and 1 µg g-1. The whole procedure, including sample preparation and SERS detection, did not exceed 30 min for a set of 6 samples. This study indicates that SERS is a promising technique for rapid tracing analysis and on-site testing of N6-BA.

Comparison and analysis of several wet scrubbing solutions to remove methyl mercaptan.

Wet scrubbing is regarded as an effective method to remove hydrophobic organic odorants. The focus of wet scrubbing is to choose an appropriate scrubbing liquid. In this study, methyl mercaptan (CH3SH) was selected as a representative hydrophobic organic odorant for treatment by wet scrubbing using several types of scrubbing solution: ethanol (C2H5OH), lead acetate ((CH3COO)2Pb), sodium hypochlorite (NaClO), and sodium hydroxide (NaOH). A comparative analysis of the treatment efficiency, operation cost, and environmental impact was conducted. Results of the technical and economic comparison indicate that the C2H5OH solution is the best choice of scrubbing solution among those tested. These findings serve as a reference for engineering design and operation for the removal of hydrophobic organic odorants.

Secreted frizzled-related protein 1 regulates the progression of neuropathic pain in mice following spinal nerve ligation.

Previous studies have shown that the Wnt/ß-catenin signaling pathway plays an important role in modulating neuropathic pain after sciatic nerve injury. In this study, we explored the role of secreted frizzled-related protein 1 (SFRP1), a Wnt antagonist, in neuropathic pain using a mouse model following spinal nerve ligation (SNL). We found SNL-induced SFRP1 downregulation in the spinal cord. Further, overexpression of SFRP1 via spinal injection into the spinal cord attenuated SNL-induced allodynia, hyperalgesia, and neuroinflammation. Consistently, in vitro assays also showed decreased expression of SFRP1 in spinal cord astrocytes after exposure to lipopolysaccharide (LPS). Overexpression of SFRP1 significantly alleviated the secretion of LPS-induced proinflammatory factors in spinal cord astrocytes. Furthermore, spinal injection of LPS-treated astrocytes induced allodynia and hyperalgesia, which were reversed by the overexpression of SFRP1 in these cells. Additionally, SNL increased Wnt3a and ß-catenin levels and also induced an increase in nuclear expression of ß-catenin; these effects were all attenuated by SFRP1. Finally, we found that downregulation of SFRP1, mainly through DNA methylation, is involved in the pathogenesis of neuropathic pain. Taken together, these results suggested that the SFRP1/Wnt3a/ß-catenin signaling pathway might be a suitable therapeutic target for neuropathic pain.

Binding of prorenin to (pro)renin receptor induces the proliferation of human umbilical artery smooth muscle cells via ROS generation and ERK1/2 activation.

INTRODUCTION: Since the discovery of the (pro)renin receptor (PRR), it has been considered as a novel bioactive molecule of the renin-angiotensin system (RAS). The activation of PRR can elicit a series of angiotensin II (AngII)-independent effects. MATERIALS AND METHODS: In this study, we investigated the effects of prorenin and PRR on the proliferation of human umbilical artery smooth muscle (HUASM) cells and explored the possible mechanisms underlying these effects. RESULTS: The binding of prorenin to PRR can promote proliferation and upregulate the anti-apoptotic protein Bcl-2 and downregulate the pro-apoptotic protein Bax independently of AngII in HUASM cells. In addition, the binding of prorenin to PRR can also increase the production of reactive oxygen species (ROS) and the phosphorylation of extracellular signal-regulated kinase (ERK1/2) independently of AngII. The pretreatment of HUASM cells with an NADPH oxidase inhibitor DPI decreased the production of ROS and also decreased the phosphorylation of ERK1/2. Furthermore, pretreatment of HUASM cells with DPI and the ERK1/2 inhibitor PD98059 significantly attenuated the prorenin-induced proliferation and regulation of apoptosis factors. CONCLUSION: Binding of prorenin to PRR can induce HUASM cell proliferation via the ROS generation and ERK1/2 activation.