Association of Serum Interleukin-8 and Serum Amyloid A With Anxiety Symptoms in Patients With Cerebral Small Vessel Disease.

Objective: Cerebral small vessel disease (CSVD) is a clinical syndrome caused by pathological changes in small vessels. Anxiety is a common symptom of CSVD. Previous studies have reported the association between inflammatory factors and anxiety in other diseases, but this association in patients with CSVD remains uncovered. Our study aimed to investigate whether serum inflammatory factors correlated with anxiety in patients with CSVD. Methods: A total of 245 CSVD patients confirmed using brain magnetic resonance imaging (MRI) were recruited from December 2019 to December 2021. Hamilton Anxiety Rating Scale (HAMA) was used to assess the anxiety symptoms of CSVD patients. Patients with HAMA scores ≥7 were considered to have anxiety symptoms. The serum levels of interleukin-1ß (IL-1ß), IL-2R, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), serum amyloid A (SAA), C-reactive protein (CRP), high-sensitivity C-reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR) were detected. We compared levels of inflammatory factors between the anxiety and non-anxiety groups. Logistic regression analyses examined the correlation between inflammatory factors and anxiety symptoms. We further performed a gender subgroup analysis to investigate whether this association differed by gender. Results: In the fully adjusted multivariate logistic regression analysis model, we found that lower levels of IL-8 were linked to a higher risk of anxiety symptoms. Moreover, higher levels of SAA were linked to a lower risk of anxiety symptoms. Our study identified sex-specific effects, and the correlation between IL-8 and anxiety symptoms remained significant among males, while the correlation between SAA and anxiety symptoms remained significant among females. Conclusions: In this study, we found a suggestive association between IL-8, SAA, and anxiety symptoms in CSVD participants. Furthermore, IL-8 and SAA may have a sex-specific relationship with anxiety symptoms.

Gut-brain axis: Focus on gut metabolites short-chain fatty acids.

Emerging evidence supports that the gut microbiome, reconsidered as a new organ in the human body, can not only affect the local gut, but also communicate with the brain via multiple pathways related to neuroendocrine, immune, and neural pathways, thereby proposing the new concept of the microbiome-gut-brain (MGB) axis. Recently, the role of short-chain fatty acids (SCFAs), which are the main anaerobic fermented metabolites of the gut microbiota in the MGB axis, has garnered significant attention. SCFAs are involved in a broad range of central neurological diseases, including neurodegenerative diseases, cerebral vascular diseases, epilepsy, neuroimmune inflammatory diseases, and mood disorders. However, the underlying mechanism of SCFA-related distant organ crosstalk is yet to be elucidated. Herein, we summarize current knowledge regarding interactions between SCFAs and the MGB axis, as well as their protective effects against central neurological diseases.

The Protective Effect of Quercetin on Endothelial Cells Injured by Hypoxia and Reoxygenation.

Background: Cerebral small vessel disease (CSVD) is a group of clinical syndromes covering all pathological processes of small vessels in the brain, which can cause stroke and serious dementia. However, as the pathogenesis of CSVD is not clear, so the treatment is limited. Endothelial cell dysfunction is earlier than clinical symptoms, such as hypertension and leukosis. Therefore, the treatment of endothelial cells is expected to be a new breakthrough. Quercetin, a flavonoid present in a variety of plants, has the function of anti-inflammation and anti-oxidation. This study aimed to investigate the protective effect of quercetin on endothelial cell injury and provide a basic theory for subsequent application in the clinic. Methods: Human brain microvascular endothelial cells (HBMECs) were cultured in vitro, and the injury model of endothelial cells was established by hypoxia and reoxygenation (H/R). The protective effects of quercetin on HBMECs were studied from the perspectives of cell viability, cell migration, angiogenesis and apoptosis. In order to further study the mechanism of quercetin, oxidative stress and endoplasmic reticulum stress were analyzed. What's more, blood-brain barrier (BBB) integrity was also studied. Results: Quercetin can promote the viability, migration and angiogenesis of HBMECs, and inhibit the apoptosis. In addition, quercetin can also activate Keap1/Nrf2 signaling pathway, reduce ATF6/GRP78 protein expression. Further study showed that quercetin could increase the expression of Claudin-5 and Zonula occludens-1. Conclusions: Our experiments show that quercetin can protect HBMECs from H/R, which contains promoting cell proliferation, cell migration and angiogenesis, reducing mitochondrial membrane potential damage and inhibiting cell apoptosis. This may be related to its antioxidation and inhibition of endoplasmic reticulum stress. At the same time, quercetin can increase the level of BBB connexin, suggesting that quercetin can maintain BBB integrity.

The Synergistic Effect of Ginkgo biloba Extract 50 and Aspirin Against Platelet Aggregation.

PURPOSE: We aimed to investigate potential synergistic antiplatelet effects of Ginkgo biloba extract (GBE50) in combination with aspirin using in vitro models. METHODS: Arachidonic acid (AA), platelet activating factor (PAF), adenosine 5'-diphosphate (ADP) and collagen were used as inducers. The antiplatelet effects of GBE50, aspirin and 1:1 combination of GBE50 and aspirin were detected by microplate method using rabbit platelets. Synergy finder 2.0 was used to analyze the synergistic antiplatelet effect. The compounds in GBE50 were identified by UPLC-Q/TOF-MS analysis and the candidate compounds were screened by TCMSP database. The targets of candidate compounds and aspirin were obtained in TCMSP, CCGs, Swiss target prediction database and drugbank. Targets involving platelet aggregation were obtained from GenCLiP database. Compound-target network was constructed and GO and KEGG enrichment analyses were performed to identify the critical biological processes and signaling pathways. The levels of thromboxane B2 (TXB2), cyclic adenosine monophosphate (cAMP) and PAF receptor (PAFR) were detected by ELISA to determine the effects of GBE50, aspirin and their combination on these pathways. RESULTS: GBE50 combined with aspirin inhibited platelet aggregation more effectively. The combination displayed synergistic antiplatelet effects in AA-induced platelet aggregation, and additive antiplatelet effects occurred in PAF, ADP and collagen induced platelet aggregation. Seven compounds were identified as candidate compounds in GBE50. Enrichment analyses revealed that GBE50 could interfere with platelet aggregation via cAMP pathway, AA metabolism and calcium signaling pathway, and aspirin could regulate platelet aggregation through AA metabolism and platelet activation. ELISA experiments showed that GBE50 combined with aspirin could increase cAMP levels in resting platelets, and decreased the levels of TXB2 and PAFR. CONCLUSION: Our study indicated that GBE50 combined with aspirin could enhance the antiplatelet effects. They exerted both synergistic and additive effects in restraining platelet aggregation. The study highlighted the potential application of GBE50 as a supplementary therapy to treat thrombosis-related diseases.