Although post-ischemic stroke process is essential for the repair of the infarcted area, excessive inflammation during this process can induce tissue damage. Damage-associated molecular patterns (DAMPs) released from injured cells in the early phase of ischemic stroke induce cytokine and chemokine production by activating microglia, thereby facilitating neutrophil and lymphocyte infiltration. However, the inhibition of neutrophils, lymphocytes, and their associated proinflammatory molecules has shown no apparent improvement in the functional outcomes and prognosis of post-ischemic stroke. Therefore, the selection of molecules and cell types that regulate cytokine production is important. Considering that the increase and infiltration of activated microglia/macrophages (M/M) is the major pathological change in ischemic stroke in humans and that DAMP/toll-like receptor (TLR) signaling is the starting point for microglial activation, the regulation of TLR signaling in M/M may be an important therapeutic strategy in the management of ischemic stroke.

We found that receptor activator of NF-κB ligand (RANKL)/receptor activator of NF-κB (RANK) signaling, expressed in activated M/Ms, inhibited DAMPs and TLR4 signaling. We also developed a partial peptide of RANKL, named microglial healing peptide 1 (MHP1), which regulates multiple TLR signaling pathways via RANK and CD14. This peptide was effective in mouse and monkey models and could be used in combination with tissue plasminogen activators in humans. Currently, we are attempting to improve the stability and efficacy of these peptides.

Drug discovery in the field of acute ischemic stroke remains challenging. Continued research on the molecular mechanisms and development of novel drugs is important for the development of drugs intended for patients with ischemic stroke.

Aortic dissection is a life-threatening condition involving tearing of the inner lining of the aorta, resulting in the separation of the layers of the aortic wall. Aortic dissection can lead to organ ischemia; however, the underlying molecular and cellular mechanisms remain poorly understood. This study examined the expression of genes associated with the promotion of aortic dissection and progression of vascular failure.

We downloaded two publicly available gene expression profiles (GSE190635 and GSE52093) from the Gene Expression Omnibus (GEO) database for the combined analysis of samples from human aortic tissue and control subjects. After identifying the differentially expressed genes (DEGs) using the GEO2R online tool, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. We also analyzed the protein-protein interactions (PPIs) of DEGs using the NetworkAnalyst online tool.

We identified 4,677 upregulated and 4,406 downregulated DEGs. Gene enrichment analysis revealed that these DEGs were mainly enriched in cell population proliferation, regulation of DNA replication, inflammatory responses, cell cycle, mitosis, and positive regulation of cell adhesion. PPI network analysis identified the following 10 hub genes: SHC1, ECT2, MCM10, EIF3C, HELLS, CDC5L, ACTB, USP9X, YWHAZ, and MAPK1. Through bioinformatics analysis, we have identified potential biomarkers and therapeutic targets for aortic dissection, providing a theoretical basis for future studies.

Background: At present, there is a paucity of evidence for the efficacy of cardioprotective (CP) drugs in improving the prognosis of patients with congenital heart disease (CHD), who are at high risk of hypertension and cardiovascular disease. CP drugs lower blood pressure (BP); therefore, in the present study we analyzed BP parameters in patients with CHD treated with and without CP drugs.

Methods and Results: A total of 60 adult patients with New York Heart Association (NYHA) class I CHD were divided into two groups - those treated with and those without CP drugs. Brachial and central BPs, radial augmentation indices, and brachial-ankle pulse wave velocities were compared between the groups. CP drugs include renin-angiotensin system blockers, as well as some beta blockers (carvedilol, metoprolol, and bisoprolol). Of the 60 patients included in the present study, 15 (25%) were treated with CP drugs. Although there was no difference in brachial systolic BP (SBP) between patients treated with CP drugs compared to those without (116.7 ± 12.5 vs.124.4 ± 19.7 mmHg, respectively; P = 0.1945), central SBP was significantly lower in patients treated with CP drugs than those without (113.2 ± 16.0 vs. 126.8 ± 21.0 mmHg, respectively; P = 0.0105). The prevalence of high central SBP was lower in the group treated with CP drugs than those without (0/15 vs. 16/45, respectively; P = 0.006), as was the prevalence of high pulse wave velocities (0/15 vs. 13/45, respectively; P = 0.0259).

Conclusions: CP drugs, when used to treat adults with CHD, lower central SBP and brachial-ankle pulse wave velocities, and therefore have the potential to improve the prognosis of patients at high risk for hypertension and cardiovascular disease.

Introduction: Retinal atherosclerosis is preceded by metabolic abnormalities and lifestyle factors. However, the most sensitive biomarkers remain unknown.

Purpose: We sought to elucidate the status of retinal arterioles in healthy men who were not treated for hypertension or metabolic diseases.

Methods: This cross-sectional study involved 733 consecutively enrolled healthy male volunteers (age, 46 ± 4 years). Fasting morning urine and blood samples were collected. Alcohol consumption and smoking status were assessed. Using the Scheie classification, fundus findings were interpreted as hypertensive and/or sclerotic changes (H/S group) or as normal (controls).

Result: Retinal arterioles were normal in 680 participants (controls), but showed hypertensive (n = 8) or sclerotic (n = 52) changes in 53 (H/S group), with overlapping hypertensive and sclerotic changes in 7. The H/S group patients were older and had a higher body mass index, systolic/diastolic blood pressure, uric acid, hemoglobin A1c, smoking index, alcohol consumption values, and a lower serum amylase level than the controls. Multivariate logistic analysis revealed significant associations between the H/S group and age (p < 0.001), systolic blood pressure (p < 0.001), uric acid levels (p = 0.011), and serum amylase levels (p = 0.010).

Conclusion: These findings suggest that high systolic blood pressure, high serum uric acid concentration, and low serum amylase level may aid the early detection of retinal atherosclerosis.

Background: The cold-sensitivity constitution (CSC), known as "Hiesho" in Japanese, is a detriment to the quality of life in young women. While CSC is associated with an imbalance in autonomic nervous activity, reflected by heart rate variability (HRV), foot baths increase parasympathetic nervous activity (PNA) as well as peripheral blood flow and epidermal temperature. In the present study, we investigated the physiological responses of young women with CSC to foot baths.

Methods: We measured the epidermal temperature of the hallux and dorsal hand, as well cutaneous blood flow at the hallux, 15 min before and 15 and 30 min after a 15-minute foot bath. HRV was also calculated.

Results: A total of 32 healthy women, assigned to either the CSC (n = 23) or non-CSC (n = 9) group, were included in the present study. After the foot bath, the epidermal temperature in the hallux increased significantly in both groups. Although the baseline hallux temperature was significantly lower in the CSC than the non-CSC group, there was no difference between the two groups after the foot bath. The baseline dorsal hand temperature was also significantly lower in the CSC than the non-CSC group; however, the foot bath significantly increased dorsal hand temperature in the CSC, but not the non-CSC, group. Cutaneous blood flow to the hallux increased significantly after the foot bath in both groups. Additionally, the PNA in the CSC group was significantly enhanced 30 min post-foot bath.

Conclusion: Foot baths in otherwise healthy young women with CSC increased the epidermal temperatures of the foot and hand. Non-localized effects of foot baths via PNA stimulation may be suggested.