Uncontrolled hypertension (HTN) is growing in incidence globally creating a critical need for alternative therapeutic strategies. Directly stimulating the carotid sinus nerve (CSN) is known to potentially reduce blood pressure (BP) but its clinical efficacy has not been consistently demonstrated with existing electrode technologies in humans. We investigated the effect of acute direct CSN stimulation on BP and HR in anesthetized humans using an application-specific multi-contact electrode. Using a novel surgical approach, a custom electrode was implanted around tissue including CSN branches in anesthetized adults. Following functional mapping, presumed baroafferent fibers were identified via response and stimulated. Outcome measures included change in systolic BP (SBP), diastolic BP (DBP), and heart rate (HR) during and after stimulation using multi-level modeling. Secondarily, dose dependency was examined. In 13 subjects, stimulation caused a 24 ± 20 mmHg (mean ± SD, p < 0.01) maximum drop in SBP, with associated drops in DBP (11 ± 9 mmHg, p < 0.01) and HR (10 ± 9 bpm, p < 0.05). In subjects with baseline SBP > 120 mmHg (n = 8), maximum SBP drop was 31 ± 23 mmHg, while subjects with baseline SBP < 120 mmHg (n = 5) exhibited a maximum SBP drop of 11 ± 3 mmHg. In all patients, BP and HR recovered rapidly with stimulus withdrawal. There were results suggesting a positive dose (electrical current) response relationship. Using a novel surgical approach and application specific electrode, direct stimulation of the carotid sinus nerve in anesthetized human subjects caused a marked concurrent drop in BP/HR followed by rapid recovery with stimulation withdrawal. There was an indication of dose dependency.This study was registered as ClinicalTrials.gov ID NCT06969846, May 9, 2025.

Intracerebral hemorrhage (ICH) leads to severe neurological deficits by disrupting brain structure and function, particularly in the sensorimotor cortex. Effective interventions to promote post-ICH brain remodeling remain limited. This study investigated the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on structural and functional remodeling in the sensorimotor networks of rats with ICH, using multi-scale analyses spanning micro-, meso-, and macro-levels.

A rat model of left basal ganglia ICH was established, followed by taVNS intervention. Structural remodeling was assessed through histology, immunofluorescence, and transmission electron microscopy. Functional remodeling was evaluated using fractional amplitude of low-frequency fluctuations (fALFF) and degree centrality (DC) analyses.

taVNS enhanced myelin repair and axonal remodeling, indicated by increased myelin basic protein (MBP) expression, reduced dephosphorylated neurofilament protein (SMI-32), and partial restoration of synaptic ultrastructure. Functional imaging showed significant longitudinal increases in zfALFF and zDC values in sensorimotor regions, including the primary and secondary motor cortices, which negatively correlated with modified neurological severity scores (mNSS).

taVNS promotes structural and functional remodeling in the sensorimotor cortex after ICH, offering a potential therapeutic strategy for neurological recovery.

Stroke is the second leading cause of death globally and a major contributor to disability. Developing countries report the highest rates of stroke, with ischemic stroke being the most prevalent type. This study aimed to explore the potential association between specific single nucleotide polymorphisms (SNPs) and thrombotic strokes in Egyptian patients, as well as the role of DNA methylation in the promoter regions of genes associated with these SNPs. The study involved 100 adult patients who were consecutively admitted to the International Medical Center. These patients, diagnosed with acute ischemic stroke, were compared to age-matched control subjects (± 3 years). Molecular analysis was conducted on six thrombosis-related SNPs: FV (R506Q, H1299R, Y1702C), FII (G20210A), and MTHFR (C677T, A1298C) using blood samples from both stroke patients and healthy controls. DNA methylation in the promoter regions of the FV, FII, and MTHFR genes was assessed through a sodium bisulfite conversion protocol and genomic DNA digestion with the methylation-dependent restriction enzyme MspJI, using specific primers for the promoter regions of FV, FII, and MTHFR in all derived samples. The biochemical analysis of the derived samples revealed elevated levels of homocysteine, ESR, and LDL in stroke patients, alongside reduced levels of both vitamin B12 and serum folate. The SNP analysis of samples from healthy controls and stroke patients, conducted using the TaqMan™ SNP genotyping assay, identified the homozygous SNPs in the FV, FII, and MTHFR genes. The results clearly show that the MTHFR C677T heterozygous mutation is present in nearly all stroke patient samples, with a very low likelihood of this mutation co-occurring with SNP mutations in the other indicated genes. Analysis of methylation activities in the promoter regions of the indicated genes showed hypermethylation in the MTHFR promoter region, while methylation levels in the FV and FII promoter regions were normal. The analysis showed increased methylation of cytosine nucleotide in the MTHFR promoter region, potentially inhibiting MTHFR expression and contributing to the development of thrombotic strokes in patients. Overall, the data support an association between the MTHFR C677T mutation, hypermethylation in its promoter region, and stroke development in the study participants.

Fluid administration is a key component in the management of acute ischemic stroke (AIS). However, the effects of different sodium concentrations in resuscitation fluids, particularly on distal organ function, remain controversial. This study compared the impact of four commonly used fluids-0.9% isotonic saline (ISO), 0.45% hypotonic saline (HYPO), 1.5% hypertonic saline (HYPER), and 5% glucose (GLUCO)-on perilesional brain tissue, lungs, and kidneys following AIS. AIS was induced in 28 male Wistar rats. Three hours after stroke induction, animals were randomized to receive one of the four fluids. In the brain, the ISO group showed significantly higher expression of versican and hyaluronan compared to the HYPER group (p = 0.022 and p = 0.018, respectively). Conversely, the HYPER group exhibited significantly elevated levels of interleukin-1β (IL-1β), vascular cell adhesion molecule-1 (VCAM-1), and zonula occludens-1 (ZO-1) compared to the GLUCO group (p = 0.01, p = 0.02, and p = 0.006, respectively). In the lungs, the ISO group demonstrated less alveolar collapse and pulmonary edema compared to the HYPER and HYPO groups (p = 0.01 and p = 0.007, respectively). In the kidneys, both the ISO and HYPO groups showed significantly less brush-border injury than the HYPER group (p = 0.007 and p = 0.032, respectively). Furthermore, blood chloride levels declined over time in the ISO group compared to the others. In conclusion, isotonic fluid administration resulted in the least amount of injury to the brain, lungs, and kidneys in this experimental model of AIS, supporting its use as a preferred resuscitation strategy in the acute phase.

The precise molecular mechanisms underlying angioedema attacks in cases of C1-inhibitor-deficient hereditary angioedema (C1-INH-HAE), angiotensin-converting enzyme inhibitor-induced angioedema (ACEi-AE), and mast cell-/histamine-mediated angioedema (Hist-AE) are not well understood. These attacks may involve immune and inflammatory mechanisms. We compared serum biomarkers indicating vascular integrity, leakage, angiogenesis, coagulation, and inflammation. During an attack-free period, we assessed 34 markers simultaneously using multi- and/or singleplex ELISA in 25 patients with C1-INH-HAE, 17 with ACEi-AE, 25 with Hist-AE, and 23 healthy controls. Differential blood counts, C1-INH-HAE-specific laboratory parameters, and recently developed assays addressing early complement and lectin pathways were included. The results revealed significant differences, as well as some similarities. Tie-2, VEGFs, C1s/C1INHc appear to play a role in all AE types regardless of whether they are bradykinin- or histamine-mediated. Furthermore, evidence was found for a role of IL-17, eosinophil, and neutrophil chemotactic factors, and the activation of these granulocytes was found. MASP-1/C1-INHc indicated early activation of the lectin pathway in ACEi-AE and HistAE, but not in C1-INH-HAE. C1s/C1-INHc and MASP-1/C1INHc ratio was able to discriminate C1-INH-HAE from controls and the other AE types. Future investigations in C1-INH-HAE, ACEi-AE, and Hist-AE should not only focus on complement activation but also the interaction with granulocytes.

Chlorogenic acid, an ester of caffeic acid and quinic acid, is found in foods such as eggplant and peaches. Its role in heart disease remains poorly understood. This study investigated whether chlorogenic acid affects cardiac hypertrophy and fibrosis in animal and cellular models of isoproterenol-induced cardiac hypertrophy. Treatment of isoproterenol-stimulated cardiomyocytes with chlorogenic acid reduced cell size and the expression levels of cardiac hypertrophy-related genes. In the animal model, isoproterenol was delivered via an osmotic minipump for 2 weeks to induce cardiac hypertrophy, and chlorogenic acid was intraperitoneally administered for the same duration. Echocardiographic analysis showed that chlorogenic acid significantly reduced wall thickness in mice. Picrosirius red staining, quantitative reverse transcription polymerase chain reaction, and Western blot analysis revealed that cardiac fibrosis was attenuated by chlorogenic acid. Chlorogenic acid treatment downregulated galectin 3 (Lgals3), a fibrosis-associated gene that had been upregulated by isoproterenol stimulation. Galectin 3 knockdown ameliorated isoproterenol-induced cardiac hypertrophy and reduced the expression levels of COL1A1 and ADAMTS8; galectin 3 overexpression increased cardiomyocyte size and upregulated COL1A1 and ADAMTS8 expression levels. These findings suggest that chlorogenic acid could serve as a novel treatment for cardiac hypertrophy and fibrosis via downregulation of galectin 3.

To evaluate the prognostic effect of a novel index by two-dimensional speckle-tracking echocardiography (STREI index) integrating right atrial (RA) and right ventricular (RV) strain in patients with immunoglobulin light chain (AL) cardiac amyloidosis.

Ninety patients were diagnosed with AL amyloidosis at Kumamoto University Hospital from 2007 to 2022. Among these patients, 70 with evidence of cardiac amyloidosis and sufficient echocardiographic data at diagnosis, including RA and RV strain analysis, were retrospectively analysed. The STREI index was developed with the following formula: [2 × RV - free wall longitudinal strain (RV - FWLS) + RA strain during the reservoir phase].

During a median follow-up of 854 days (interquartile range, 151-1787 days), 33 deaths occurred. The STREI index was significantly lower in the all-cause death group than in the survival group (40.5 ± 19.9 vs. 57.7 ± 18.9, p < 0.01). The STREI index was significantly and independently associated with all-cause death after adjusting for left ventricular global longitudinal strain and left atrial strain during the reservoir phase (hazard ratio: 0.96, 95 % confidence interval: 0.93-0.98, p < 0.01). The optimal cut-off value was an STREI index of 50 % (sensitivity: 78 %, specificity: 72 %, area under curve: 0.80) to predict all-cause mortality using receiver operating characteristic analysis. A Kaplan-Meier analysis showed a significantly higher risk of all-cause death and cardiovascular death in patients with a low STREI index (<50 %, n = 32) than in those with a high STREI index (≥50 %, n = 38) (both p < 0.01).

The STREI index, which is a new index of total right heart function, might be useful for predicting the prognosis in patients with AL cardiac amyloidosis.

Cardiometabolic diseases (CMD) encompass a cluster of cardiovascular disorders primarily driven by metabolic dysregulation, such as obesity-associated cardiomyopathy, hypertensive heart disease, and diabetic cardiomyopathy. The pathogenesis of CMD is closely linked to chronic inflammation, myocardial hypertrophy, and mitochondrial energy metabolism dysfunction. Recently, the succinate-GPR91 pathway, a critical hub for metabolic regulation, has gained attention for its role in CMD. In addition to its function as an intermediate in the TCA cycle, succinate also exerts a range of pathophysiological effects by acting as a signaling molecule through the activation of its receptor, GPR91.Studies indicate that in metabolic disorders such as obesity, hypertension, diabetes,and atherosclerosis, abnormal activation of the succinate-GPR91 axis exacerbates inflammation, accelerates myocardial hypertrophy, and induces mitochondrial dysfunction, contributing to cardiovascular damage. Targeting the succinate-GPR91 pathway may offer novel CMD therapies. This article reviews succinate's role in inflammation, hypertrophy, mitochondrial dysfunction, and other diseases, offering insights for CMD research and treatment.

Health and safety issues in micro and small enterprises (MSEs) are recognized as a global challenge. This study aimed to examine Workers' Health Centers (WHCs) as a representative public organization providing occupational health services to MSEs in Korea. WHCs were established in 2011 after a trial period aimed at addressing occupational diseases in MSEs with limited resources. As of 2024, there are 24 WHCs, 22 branch offices, and 23 trauma counseling centers for workers. These health centers are managed by the Korea Occupational Safety and Health Agency, with their actual operation delegated to private organizations. Each WHC employs an average of 13 staff members and is organized into four specialized teams: cardiovascular disease prevention, workplace environment improvement, musculoskeletal disease prevention, and occupational stress management. These centers also offer common basic programs along with region-specific specialized initiatives. In 2023, the total cumulative number of users reached 203,877, with employees from MSEs comprising approximately 88.5% of the total. WHCs can thus be seen as playing a pivotal role as case managers of health requirements in the workplace by fostering strong relationships with MSEs and linking them to other relevant programs through a problem-solving-oriented approach. Given the limited resources of these enterprises, proactive policies and the equitable application of safety and health regulations are essential. A balanced strategy that combines regulatory enforcement with practical assistance is critical to ensure the success of WHCs in improving health and safety conditions in MSEs.