Atomized inhalation of Icaritin reduces airway inflammation and remodeling in asthmatic mice.

BACKGROUND: Asthma is a disease characterized by airway hyperresponsiveness and airway inflammation. Icaritin (ICT) is a plant hormone with various pharmacological activities such as anti-inflammatory, immune regulation, and anti-tumor. This study mainly explored the effects of nebulized inhalation of ICT on airway inflammation and airway remodeling in asthmatic mice. METHOD: Different groups of ovalbumin (OVA)-induced asthma mice with acute and chronic airway inflammation received ICT. Asthmatic mice received budesonide (BDND) aerosol inhalation as a positive control, while normal control and asthma model mice received the same volume of saline. Following finishing of the study, analyses were conducted on behavioral tests, biochemical indices, and histological structures of lung tissues. RESULTS: Aerosol inhalation of ICT can notably reduce inflammatory cells infiltration around the airways and pulmonary vessels, and suppressed goblet cell hyperplasia in asthmatic mice. Long-term inhalation of ICT can decrease airway collagen deposition and airway smooth muscle hyperplasia, and alleviate airway hyperresponsiveness, mirroring the effects observed with hormone employed in clinical practice. CONCLUSION: Nebulized inhalation of ICT can effectively inhibit airway inflammation in asthmatic mice, improve airway remodeling, and reduce airway hyperresponsiveness, with effects similar to those of hormones. It may serve as a potential candidate used as a hormone replacement asthma treatment.

Genetically determined blood pressure, antihypertensive medications, and risk of intracranial aneurysms and aneurysmal subarachnoid hemorrhage: A Mendelian randomization study.

INTRODUCTION: Observational studies suggest that different classes of antihypertensive drugs may have different effects on the occurrence of intracranial aneurysms (IA) and subarachnoid hemorrhage (SAH). However, the reported results in previous studies are inconsistent, and randomized data are absent. We performed a two-sample Mendelian randomization (MR) analysis to study the causal effects of genetically determined blood pressure (BP) and genetic proxies for antihypertensive drug classes on the risk of IA and SAH. MATERIALS AND METHODS: Genetic instruments and outcome data were obtained from independent genome-wide association studies (GWAS) or published data, which were exclusively restricted to European ancestry. Causal relationships were identified using inverse-variance weighted MR analyses and a series of statistical sensitivity analyses. The FinnGen consortium was used for repeated analysis to verify results obtained from the above GWAS. RESULTS: Two-sample MR analysis showed that genetically determined Systolic BP, Dystolic BP, and Pulse Pressure were related to a higher risk of IA and SAH. Based on identified single nucleotide polymorphisms (SNPs) that influence the effect of calcium channel blockers (CCB, 42 SNPs), beta-blockers (BB, 8 SNPs), angiotensin-converting enzyme inhibitors (ACEI, 2 SNPs), angiotensin receptor blockers (ARB, 1 SNPs), and thiazides (5 SNPs), genetically determined effect of CCBs was associated with a higher risk of IA (OR, 1.07 [95% CI, 1.03-1.10], p = 5.02 × 10-5) and SAH (OR, 1.06 [95% CI, 1.03-1.09], p = 1.84 × 10-3). No associations were found between other antihypertensive drugs and the risk of IA or SAH. The effect of CCBs on SAH was confirmed in FinnGenconsortium samples (OR, 1.04 [95% CI, 1.00-1.08], p = 0.042). DISCUSSION AND CONCLUSION: This MR analysis supports the role of elevated blood pressure in the occurrence of intracranial aneurysms and subarachnoid hemorrhage. However, genetic proxies for calcium channel blockers were associated with an increased risk of intracranial aneurysms and subarachnoid hemorrhage. Further studies are required to confirm these findings and investigate the underlying mechanisms.

[Preparation of chloro-sparfloxacin and its fluorescence behavior].

Sparfloxacin (SPFX) can be oxidized by nitrous acid then react with chlorohydric acid further to form a strong fluorescence substance in acid media. The molecular structure is identified by elemental analysis, IR, MS and fluorescence spectra. The emission properties of sparfloxacin and chloro-sparfloxacin are greatly distinct, the fluorescence of sparfloxacin is so weak that it can not be determined by means of fluorescence spectra, but the fluorescence intensity of the new substance is 110 fold more than that of sparfloxacin itself. With quinine sulfate (0.05 mol.L-1 of H2SO4, phi f = 0.55) as standard solution, the fluorescence quantum production rate of SPFX and this new fluorescence were determined as 0.0072 and 0.1539, respectively. By this, a new sensitive method for the determination of SPFX tablets by fluorescence spectroscopy is presented with good result. The recovery of method is 97.2%. RSD is 1.6%. Finally, the fluorescence self quenching and chloro-sparfloxacin enhancement mechanism of sparfloxacin are explored in detail.