Sodium tanshinone IIA sulfonate protects vascular relaxation in ApoE-knockout mice by inhibiting the SYK-NLRP3 inflammasome-MMP2/9 pathway.

BACKGROUND: Hyperlipidemia damages vascular wall and serves as a foundation for diseases such as atherosclerosis, hypertension and stiffness. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is implicated in vascular dysfunction associated with hyperlipidemia-induced vascular injury. Sodium tanshinone IIA sulfonate (STS), a well-established cardiovascular protective drug with recognized anti-inflammatory, antioxidant, and vasodilatory properties, is yet to be thoroughly investigated for its impact on vascular relaxant imbalance induced by hyperlipidemia. METHODS: In this study, we treated ApoE-knockout (ApoE-/-) mouse with STS and assessed the activation of the NLRP3 inflammasome, expression of MMP2/9, integrity of elastic fibers, and vascular constriction and relaxation. RESULTS: Our findings reveal that STS intervention effectively preserves elastic fibers, significantly restores aortic relaxation function in ApoE-/- mice, and reduces their excessive constriction. Furthermore, STS inhibits the phosphorylation of spleen tyrosine kinase (SYK), suppresses NLRP3 inflammasome activation, and reduces MMP2/9 expression. CONCLUSIONS: These results demonstrate that STS protects vascular relaxation against hyperlipidemia-induced damage through modulation of the SYK-NLRP3 inflammasome-MMP2/9 pathway. This research provides novel insights into the mechanisms underlying vascular relaxation impairment in a hyperlipidemic environment and uncovers a unique mechanism by which STS preserves vascular relaxation, offering valuable foundational research evidence for its clinical application in promoting vascular health.

Efficacy of Electronic Cigarettes vs Varenicline and Nicotine Chewing Gum as an Aid to Stop Smoking: A Randomized Clinical Trial.

Importance: Electronic cigarettes (ECs) are often used by smokers as an aid to stopping smoking, but evidence is limited regarding their efficacy compared with nicotine replacement therapy (NRT), and no evidence is available on how their efficacy compares with that of varenicline. Objective: To evaluate whether ECs are superior to NRT and noninferior to varenicline in helping smokers quit. Design, Setting, and Participants: This was a randomized clinical trial conducted at 7 sites in China and including participants who were smoking at least 10 cigarettes per day and motivated to quit, not using stop-smoking medications or EC, and willing to use any of the study products. Participants were first recruited in May 2021, and data analysis was conducted in December 2022. Interventions: A cartridge-based EC (30 mg/mL nicotine salt for 2 weeks and 50 mg/mL after that), varenicline (0.5 mg, once a day for 3 days; 0.5 mg, twice a day for 4 days; and 1 mg, twice a day, after that), and 2 mg (for smokers of ≤20 cigarettes per day) or 4 mg (>20 cigarettes per day) nicotine chewing gum, all provided for 12 weeks and accompanied by minimal behavioral support (an invitation to join a self-help internet forum). Main Outcomes and Measures: The primary outcome was sustained abstinence from smoking at 6 months as validated by an expired-air carbon monoxide reading (<8 parts per million). Participants lost to follow-up were included as nonabstainers. Results: Of 1068 participants, 357 (33.5%) were female, and the mean (SD) age was 33.9 (3.1) years. A total of 409 (38.3%), 409 (38.3%), and 250 (23.4%) participants were randomized to the EC, varenicline, and NRT arms, respectively. The 6-month biochemically validated abstinence rates were 15.7% (n = 64), 14.2% (n = 58), and 8.8% (n = 22) in the EC, varenicline, and NRT study arms, respectively. The quit rate in the EC arm was noninferior to the varenicline arm (absolute risk reduction, 1.47%; 95% CI, -1.41% to 4.34%) and higher than in the NRT arm (odds ratio, 1.92; 95% CI, 1.15-3.21). Treatment adherence was similar in all study arms during the initial 3 months, but 257 participants (62.8%) in the EC arm were still using ECs at 6 months, with no further use in the 2 other study arms. The most common adverse reactions were throat irritation (32 [7.8%]) and mouth irritation (28 [6.9%]) in the EC arm, nausea (36 [8.8%]) in the varenicline arm, and throat irritation (20 [8.0%]) and mouth irritation (22 [8.8%]) in the NRT arm. No serious adverse events were recorded. Conclusions and Relevance: The results of this randomized clinical trial found that when all treatments were provided with minimal behavior support, the efficacy of EC was noninferior to varenicline and superior to nicotine chewing gum. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2100048156.

Oridonin Alters Hepatic Urea Cycle via Gut Microbiota and Protects against Acetaminophen-Induced Liver Injury.

Acetaminophen (APAP) hepatotoxicity is the leading cause of acute liver failure in the western world. Oridonin (OD), which is the major active ingredient of the traditional Chinese medicine Rabdosia rubescens, reportedly exerts anti-inflammatory and antioxidative effects. Here, we first find that OD protects against APAP-induced hepatotoxicity. The results of hepatic tissue-associated RNA-seq and metabolomics showed that the protective effects of OD were dependent upon urea cycle regulation. And such regulation of OD is gut microbiota partly dependent, as demonstrated by fecal microbiota transplantation (FMT). Furthermore, using 16S rRNA sequencing, we determined that OD significantly enriched intestinal Bacteroides vulgatus, which activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to regulate redox homeostasis against APAP by urea cycle. In conclusion, our study suggests that the Bacteroides vulgatus-urea cycle-Nrf2 axis may be a potential target for reducing APAP-induced liver injury, which is altered by OD.

Characterization of magnetic domain walls using electron magnetic chiral dichroism.

Domain walls and spin states of permalloy were investigated by electron magnetic chiral dichroism (EMCD) technique in Lorentz imaging mode using a JEM-2100F transmission electron microscope. EMCD signals from both Fe and Ni L3,2 edges were detected from the Bloch lines but not from the adjacent main wall. The magnetic polarity orientation of the circular Bloch line is opposite to that of the cross Bloch line. The orientations of Fe and Ni spins are parallel rather than antiparallel, both at the cross Bloch line and circular Bloch line.

Prevalence and progression of myopic retinopathy in Chinese adults: the Beijing Eye Study.

PURPOSE: To determine the prevalence and progression of myopic retinopathy in Chinese adults. DESIGN: Population-based cross-sectional study. PARTICIPANTS: The Beijing Eye Study 2001 included 4439 subjects of 5324 individuals who were invited to participate (response rate, 83.4%); the eligibility criterion was an age of 40+ years. The study was repeated in 2006, with 3251 subjects (73.2%) participating. METHODS: The participants underwent a detailed eye examination, including fundus photography. Myopic retinopathy was defined by posterior staphylomata, lacquer cracks, Fuchs' spot of the macula, and myopic chorioretinal atrophy at the posterior pole. Parapapillary atrophy was assessed separately. MAIN OUTCOME MEASURES: Prevalence of myopic retinopathy and its change during a follow-up of 5 years. RESULTS: After exclusion of pseudophakic or aphakic eyes, and eyes without assessable fundus photographs, 4319 subjects (97.3%) were included in the present study. Myopic retinopathy was present in 198 eyes (2.3%+/-0.2%; 95% confidence interval [CI], 2.0-2.6) of 132 participants (3.1%). Myopic retinopathy was significantly associated with higher age (P<0.001), worse best-corrected visual acuity (P<0.001), deeper anterior chamber (P = 0.04), larger optic disc (P<0.001), less age-related macular degeneration (P = 0.02; odds ratio [OR] 0.90), and greater prevalence of open-angle glaucoma (P<0.001; OR 4.42). Myopic retinopathy was not associated significantly (P>0.20) with body height and weight, gender, rural versus urban region of residence, level of education, intraocular pressure, or central corneal thickness. The prevalence of myopic retinopathy increased significantly (P<0.001) with increasing myopic refractive error, from 3.8% in eyes with a myopic refractive error of < -4.0 diopters to 89.6% in eyes with a myopic refractive error of at least -10.0 diopters. At the 5-year follow-up examination, enlargement of the chorioretinal atrophy at the posterior fundus was observed in 9% of the eyes. CONCLUSIONS: Myopic retinopathy was present in 3.1% of subjects aged 40+ years who resided in the Greater Beijing area. Myopic retinopathy was associated with increased age, worse best-corrected visual acuity, deeper anterior chamber, larger optic disc, less age-related macular degeneration, and higher prevalence of open-angle glaucoma.

Underdevelopment of optic radiation in children with amblyopia: a tractography study.

PURPOSE: To detect the abnormalities of the optic radiation (OR) in children with amblyopia by diffusion tensor imaging (DTI) and tractography. DESIGN: Prospective, nonrandomized clinical trial. METHODS: Fourteen children with amblyopia and 14 normally sighted children underwent DTI scanning. After the ORs were reconstructed by using tractography algorithm, voxels through which the anterior parts of ORs passed were determined for their values of fractional anisotropy (FA). The paired t test was applied to compare their mean FA values of right OR and left OR in the control group. For the amblyopia group, analysis of variance was conducted to determine the effect of laterality and vision status on the FA values. In addition, the voxel numbers of anterior and posterior parts of both ORs were calculated. The Student t test was used to compare the average FA of bilateral ORs and voxel numbers between the two groups. RESULTS: Comparison demonstrated left-higher-than-right asymmetry in both amblyopic children and normal children. We found no significant difference of average FA between the amblyopic group (0.4832 +/- 0.0225) and control group (0.4770 +/- 0.0273). Voxel numbers of the anterior parts of both ORs were not significantly different between the two groups, whereas voxel numbers of their posterior parts in the controls were more than that of amblyopic children. CONCLUSION: Tractography showed more voxels in the posterior ORs of normal children than in the amblyopic children, indicating that normal children have better development of the ORs. The underdevelopment of the ORs might reflect the dysfunction of visual cortex in children with amblyopia.

Detection of abnormal visual cortex in children with amblyopia by voxel-based morphometry.

PURPOSE: To detect the abnormalities of gray matter in children with amblyopia by voxel-based morphometry (VBM). DESIGN: Prospective, nonrandomized clinical trial. METHODS: Thirteen children with amblyopia and 14 normally sighted children underwent magnetic resonance (MR) examination. The two groups were age-matched with a mean age of 5.8 years. In the amblyopia group, five children had strabismus amblyopia, and eight had anisometropic amblyopia. We analyzed the original 3-dimensional T1 brain images using the VBM module within the widely used analysis software package SPM2 (Welcome Department of Cognitive Neurology, London, United Kingdom). After normalization, segmentation, and smoothing of the images, comparison between amblyopic and control groups was derived for the gray matter of the entire brain using parametric statistics. RESULTS: The results of VBM analysis indicated that the amblyopic group had decreased gray matter density in the middle frontal gyrus, parahippocampal gyrus, fusiform gyrus, inferior temporal gyrus of the left hemisphere, and the bilateral calcarine cortices. The radii of these regions ranged from 12 to 36 voxels. These abnormalities were consistent with morphologic changes in brain regions related to visual function. CONCLUSIONS: Using MR and VBM analysis, we detected morphologic changes in the visual cortex of children with amblyopia, which may indicate developmental abnormalities of visual cortex during the critical growth period.