Search Results (2,633)

Background: Ischemic stroke has been reported rarely after coronavirus disease 2019 (COVID-19) vaccination, most clearly in association with vaccine-induced immune thrombotic thrombocytopenia (VITT). Nevertheless, temporal proximity alone cannot establish causality, particularly when conventional vascular risk factors are present. We report a case of posterior circulation ischemic stroke occurring 36–48 h after first-dose ChAdOx1 nCoV-19/AZD1222 vaccination without VITT and provide a focused narrative review of the clinical, epidemiological, and mechanistic evidence regarding post-vaccination stroke. Methods: Clinical, laboratory, and neuroimaging data were reviewed retrospectively. A focused narrative literature review was performed to contextualize VITT-related and non-VITT ischemic stroke after COVID-19 vaccination, pharmacovigilance signals, population-based evidence, and proposed biological mechanisms. Results: A 63-year-old man with well-controlled hypertension and a remote history of smoking developed systemic symptoms within 24 h of first-dose ChAdOx1 nCoV-19/AZD1222 vaccination, followed by severe hypertension and acute posterior circulation neurological symptoms 36–48 h after vaccination. Neuroimaging showed an acute left cerebellar infarct extending into the middle cerebellar peduncle, with approximately 50% stenosis of the intradural left vertebral artery. Platelet counts remained normal, D-dimer and anti-PF4 antibody testing were normal, SARS-CoV-2 polymerase chain reaction (PCR) testing was negative, and routine cardiac evaluation did not identify a definite cardioembolic source. Conclusions: This case highlights an early posterior circulation ischemic stroke temporally associated with ChAdOx1 nCoV-19/AZD1222 vaccination in the absence of VITT. Although individual causality cannot be established from a single case, careful reporting of such presentations may improve clinical recognition, etiological evaluation, and pharmacovigilance. Full article

Background and Clinical Significance: Marfan syndrome (MFS) is an autosomal-dominant connective-tissue disorder caused by pathogenic FBN1 variants. Aortic-root dilation and dissection are the canonical complications, whereas spontaneous vertebral artery dissection (VAD) is described only sporadically. Yet, cerebrovascular events are several-fold more common in MFS, and up to 74% of patients exhibit increased vertebral artery tortuosity, a validated predictor of dissection; Case Presentation: A 32-year-old African man with hypertension, type 2 diabetes mellitus, tobacco use, and headaches labelled as migraine presented with acute agitation, visual disturbance, vertigo, dysarthria, and right-sided weakness of two hours’ duration. Examination disclosed previously unrecognised marfanoid stigmata: arachnodactyly with positive wrist and thumb signs, reduced upper-to-lower segment ratio, increased arm-span-to-height ratio, dolichocephaly, pectus excavatum, and a high-arched palate. Non-contrast CT showed left occipital and posterior inferior cerebellar hypodensities. CT angiography demonstrated discontinuous intraluminal filling defects in the left vertebral artery at C4 and C2, and MR angiography confirmed long-segment occlusion/stenosis of the intracranial left vertebral artery. Echocardiography revealed mild aortic-root dilation (4.0 cm; Z-score +2.53) and a small patent foramen ovale (PFO) with a positive bubble study. The patient received intravenous thrombolysis followed by antiplatelet therapy, a high-intensity statin, antihypertensive therapy, and intensified glycaemic control. Because the infarct territory matched the dissected vessel and the small PFO carried no high-risk features (RoPE score 6; PASCAL category “unlikely”), VAD was designated the culprit lesion and the PFO incidental; Conclusions: Spontaneous VAD may be the inaugural manifestation of unrecognised MFS, antedating aortic complications. In young adults with cryptogenic posterior-circulation stroke and marfanoid features, early cervical imaging and Ghent assessment are warranted, and a coexistent PFO should not be assumed causal. Multidisciplinary evaluation supports accurate attribution and surveillance. Full article

Chronic pulmonary diseases, including chronic obstructive pulmonary disease (COPD), idiopathic interstitial pneumonias (IIPs), pulmonary arterial hypertension (PAH), and pulmonary tuberculosis (PTB), are all marked by persistent immune imbalance, inflammation, and tissue injury. Despite the known anti-inflammatory and antioxidant properties of sea buckthorn, its protective mechanisms across these conditions remain poorly defined. We obtained active compounds and predicted targets from TCMSP and SwissTargetPrediction, and integrated disease genes from GeneCards and CTD with transcriptomic evidence from differential expression analysis and WGCNA. Using SVM-RFE, random forest, and LASSO, we identified hub genes and performed enrichment, immune infiltration, molecular docking, and molecular dynamics analyses. Our results showed that quercetin, kaempferol, and isorhamnetin were the core compounds linked to immune- and inflammation-related targets. The four diseases shared involvement in Toll-like receptor, NOD-like receptor, and related inflammatory pathways, along with recurrent alterations in myeloid cells. Besides, results from molecular docking and molecular dynamics simulations also suggested relatively stable interactions between key compounds and protein targets. Overall, these findings suggest that sea buckthorn may have potential pharmacological relevance across chronic lung diseases. It might do so by modulating common inflammatory signaling pathways and myeloid-related immune responses. At the same time, these findings provide a basis for further experimental validation. Full article

Background/Objectives: Arterial hypertension (AH) and hepatitis C virus (HCV) infection are interlinked, with AH increasing the risk of severe liver disease and HCV contributing to cardiovascular issues. Treating HCV in hypertensive patients is critical, though data on direct-acting antivirals (DAAs) in this group remain limited. Methods: This retrospective study evaluated the effects of DAAs in AH patients with HCV using data from the 2015–2023 EpiTer-2 project, a multicenter study in Poland. Results: Among the 18,968 HCV-infected DAA-treated patients, 5976 had AH. These patients were older, predominantly women, and had higher rates of obesity, comorbidities, cirrhosis, hepatocellular carcinoma, and genotype 1b infection. Sustained virologic response rates were high and comparable between the AH and non-AH groups in the intent-to-treat (94.8% vs. 94.2%) and per-protocol analyses (97.6% vs. 97.6%). AH was not independently associated with treatment failure (OR 0.87, 95% CI: 0.69–1.10). Predictors of failure included genotype 3, decompensated liver function, cirrhosis, thrombocytopenia, and treatment with asunaprevir + daclatasvir. While therapy discontinuation was more common in the AH patients, most completed treatment, with fatigue being the most frequent adverse event. Although not directly evaluated, the overall safety outcomes suggest that potential drug–drug interactions with antihypertensive therapies are unlikely to have a major clinical impact in routine practice. Conclusions: This study highlights the safety and efficacy of DAAs in AH patients and emphasizes the importance of early HCV detection and treatment in this population. Full article

Background: Hyperuricemia is increasingly recognized as an important component of metabolic dysfunction and cardiometabolic risk, particularly in individuals with obesity and hypertension. However, the relative contribution of obesity-related metabolic disturbances and blood pressure parameters to serum uric acid levels remains incompletely understood. The aim of this study was to identify independent clinical and metabolic determinants of serum uric acid levels and to determine whether obesity or hypertension is more strongly associated with elevated serum uric acid levels. Methods: This retrospective observational study evaluated the metabolic determinants of serum uric acid levels in 370 hospitalized adults stratified according to obesity and hypertension status. Serum uric acid concentrations were measured using an enzymatic spectrophotometric method and compared across four clinical groups, and univariate and multivariable analyses were performed to identify independent determinants of serum uric acid levels. Allopurinol use was recorded and included in the multivariable analysis, whereas the effects of individual antihypertensive drug classes were not evaluated. Results: Hyperuricemia was identified in 16.8% of the cohort, with the highest prevalence observed among patients with coexisting obesity and hypertension (22%). Serum uric acid levels were higher in men than in women (median: 6.4 vs. 5.7 mg/dL; p < 0.001). In the multivariable analysis, higher expected serum uric acid levels were independently associated with higher BMI, higher ALT activity, eGFR ≤ 90 mL/min/1.73 m², and male sex, whereas older age and not receiving allopurinol were independently associated with lower expected serum uric acid levels. Each 1 kg/m² increase in BMI was associated with an approximately 0.48% higher expected serum uric acid level (95% CI: 0.19–0.78%; p = 0.001). Blood pressure parameters were not significant predictors. Conclusions: These findings suggest that excess adiposity and associated metabolic disturbances may play a more prominent role than hypertension alone in the development of hyperuricemia. Targeting obesity and metabolic risk factors may therefore represent an important strategy for reducing hyperuricemia and improving cardiometabolic health. Full article

Hypertension is a prevalent disorder that results in millions of deaths worldwide. In this regard, timely diagnosis and effective treatment are paramount for maintaining optimal blood pressure levels in the early stages of the disease. The objective of the present study was to synthesize and assess the effect of peptides derived from chia seeds that had undergone fermentation with Lacticaseibacillus paracasei strain 2501 (hereinafter referred to as LPDP, i.e., L. paracasei-derived products from this fermentation) on the angiotensin-converting enzyme (ACE) and the spontaneously hypertensive rat model (SHR). LPDP exhibited competitive inhibition, as evidenced by the identification of seven peptides in the <1 kDa fraction by HPLC-QToF-MS. The LPDP exhibited an IC₅₀ of 11.1 μg/mL on ACE. The oral administration of 50 mg/kg body weight (BW) to SHR over a 14-day period resulted in a significant reduction in systolic pressure from 152 to 87 mmHg, accompanied by a substantial decrease in diastolic pressure from 117 to 74 mmHg. It is noteworthy that doses of 500 mg/kg BW led to a significant reduction in systolic pressure, from 154 to 68 mmHg and diastolic pressure, from 117 to 42 mmHg under identical experimental conditions. The hematological profiling of the assayed animals revealed that LPDP has no adverse effects at the cellular or biochemical level. These findings indicate the anti-hypertensive properties of LPDP and its possible application in the treatment of blood pressure. Full article

Background/Objectives: Diabetes mellitus type 2 (T2DM) is often associated with hypertension, necessitating treatment with combinations of medications that address both glycemic control and blood pressure. Whether commonly co-prescribed antihypertensives modify the glycemic efficacy of a sulfonylurea remains insufficiently characterized in controlled preclinical models. Methods: One hundred adult male Wistar rats were allocated to ten parallel groups (n = 10): healthy and diabetic untreated controls; glimepiride, bisoprolol or amlodipine monotherapy (in healthy and diabetic animals); and the diabetic combinations glimepiride+bisoprolol and glimepiride+amlodipine. T2DM was induced with a high-fat diet plus low-dose streptozotocin (35 mg/kg, i.p.) and confirmed by fasting blood glucose ≥ 200 mg/dL. Glycated hemoglobin (HbA1c) was measured weekly for 11 weeks. Non-parametric inference (Kruskal–Wallis, Dunn’s with Bonferroni correction, Mann–Whitney U, Wilcoxon signed-rank) was complemented by Random Forest regression and PCA/K-means clustering. Results: Week-11 HbA1c differed markedly across groups (Kruskal–Wallis H = 94.3, p < 0.001). Glimepiride + bisoprolol achieved near-normal control (4.37% ± 0.15), statistically indistinguishable from healthy groups (p ≥ 0.33), and was the only diabetic regimen with a declining trajectory (−0.66 percentage points; Wilcoxon p = 0.004). Adding either antihypertensive to glimepiride did not worsen glycemic control. Amlodipine monotherapy did not attenuate hyperglycemia (8.47% ± 0.20), approaching that of untreated diabetic controls (9.31% ± 0.18), consistent with the absence of intrinsic glucose-lowering activity. All agents showed pronounced disease-state dependence (healthy–diabetic divergence 2.33–3.13 points). Random Forest prediction was accurate (R² = 0.985), and unsupervised clustering separated effective from ineffective regimens, corroborating the statistical findings. Conclusions: In this model, bisoprolol co-administration enhanced and amlodipine co-administration preserved glimepiride-mediated glycemic control. Glimepiride+bisoprolol emerged as the most effective regimen, supporting cardioselective β-blockade as a metabolically favorable antihypertensive partner for sulfonylurea therapy and warranting clinical confirmation. More broadly, these results provide a preclinical, evidence-based rationale for selecting metabolically favorable antihypertensives in patients with coexisting T2DM and hypertension, with the potential to improve glycemic outcomes and reduce the risk of adverse drug–disease interactions during combination therapy. Full article

Introduction: Arterial hypertension (AH) is one of the leading public health issues worldwide, and patients’ adherence to recommended treatment is essential for successful regulation of blood pressure (BP), disease control, and prevention of complications. Aim: The aim of this study was to evaluate the adherence of patients with hypertension to medication and lifestyle changes in Croatia, based on the primary care arm of the EUROASPIRE V survey. Methods: A cross-sectional study was conducted in nine family medicine practices in the city of Zagreb, following the protocol of the EUROASPIRE V primary care study. Out of the total Croatian cohort of 203 participants, data on 156 participants with AH were included in this study. The study used components of the EUROASPIRE V questionnaire on self-assessment of adherence to medications, existing lifestyle characteristics and self-reported lifestyle changes (smoking, salt intake, and physical activity, respectively). Results: A total of 156 participants were included, with almost even distribution of men (n = 77, 49.4%) and women (n = 79, 50.6%); median age was 65 (57, 72). A self-reported medication adherence to antihypertensive medication of 100% (all of the time) was reported by 56.9% patients. According to the lifestyle change questionnaire, the highest adherence was concerning reduction in salt intake (74.4%), while smoking was reduced in 24.1% of advised participants with AH, 13.8% had quit smoking, and increased physical activity was reported by 24.4% patients. Conclusions: The results of the primary care arm of EUROASPIRE V study in Croatia on treated patients with AH indicate suboptimal BP control in a significant proportion of patients (55.1%) and suboptimal lifestyle change adherence. Achieving target BP and optimal disease control requires additional efforts to foster patients’ adherence to prescribed medications and lifestyle recommendations. Full article

Hypertension threatens the health of aging captive giant pandas, yet its molecular signatures remain poorly characterized. Here, multi-omics sequencing was applied to explore the molecular regulatory process of hypertension and the pharmacodynamic effect of levamlodipine on this endangered species. Six aged giant pandas were divided into hypertensive and normotensive groups (three hypertensive and three normotensive pandas) based on clinical phenotypes and blood pressure measurements. A multi-omics approach was employed, including blood RNA-seq, Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq), single-cell RNA-seq (scRNA-seq) of peripheral blood mononuclear cells, and time-series RNA-seq following levamlodipine administration. Our transcriptomic analysis revealed a statistically significant decline in ACE2 transcript abundance (Padj < 0.05), which suggests a possible shift in renin–angiotensin system signaling linked to hypertensive status in giant pandas. Single-cell analysis of 88,693 cells revealed that hypertension-associated genes were predominantly enriched in monocytes and T cells, implicating immune cell activation. Time-dependent transcriptional changes after levamlodipine administration. Temporal gene dynamics showed early activation of metabolic pathways followed by delayed inhibition of ion channels and calcium signaling. This study provides a transcriptional molecular perspective into the pathogenesis of hypertension in giant pandas, which is conducive to developing more effective antihypertensive treatment strategies, thereby protecting the health of this endangered species. Full article

In this study, Apocynum venetum was employed as the raw material to optimize protein extraction and enzymatic hydrolysis processes for the preparation of highly active angiotensin-converting enzyme (ACE)-inhibitory peptides, achieving an ACE inhibition rate of 92.34%. Multispectral analyses and microstructural characterization demonstrated that enzymatic hydrolysis induced the unfolding of protein secondary structures, resulting in a looser and more porous morphology enriched with characteristic amino acids. A total of 2567 peptide sequences were identified by LC–MS/MS, among which 18 potential bioactive peptides were screened. Molecular docking analysis revealed that these peptides interact with the active site of ACE primarily through hydrogen bonding and hydrophobic interactions, with WLRDFL exhibiting the strongest binding affinity. This study systematically elucidates the structural characteristics and antihypertensive molecular mechanisms of ACE-inhibitory peptides derived from Apocynum venetum, providing both theoretical insights and experimental support for the development of natural antihypertensive functional foods and the high-value utilization of this plant. Full article

Hypertension or high blood pressure drives structural and functional cardiac remodelling through sustained pressure overload, oxidative stress, and chronic inflammation. Lifestyle modifications including regular exercise and a healthy diet including fruits and vegetables help in attenuating high blood pressure. Berries are small fruits abundant in polyphenols, vitamins and minerals which provide these fruits with antioxidant and anti-inflammatory properties. One such berry is the Saskatoon berry (Amelanchier alnifolia), which is rich in anthocyanins and procyanidins with demonstrated cardiometabolic activity, yet its effects on hypertension and cardiac remodelling have not been studied. This study evaluated the impact of 16-week Saskatoon berry supplementation on cardiovascular structure, function, inflammation, and oxidative stress in spontaneously hypertensive rats (SHRs). Age-matched Wistar Kyoto (WKY) rats served as normotensive controls. Saskatoon berry supplementation did not significantly lower systolic or diastolic blood pressure in SHRs; however, echocardiography results revealed trends towards attenuation of hypertensive cardiac remodelling. Saskatoon berry supplementation reduced interventricular septal and posterior wall thickness, decreased left ventricular (LV) mass, and partially preserved systolic function, as reflected by improved ejection fraction and fractional shortening. Diastolic relaxation (IVRT) remained impaired, indicating selective effects on systolic rather than lusitropic function. Serum TNF-α and TBARS were not significantly altered, whereas IL-10 was partially restored, suggesting a modest improvement in systemic inflammatory balance. Principal component analysis integrating all hemodynamic, echocardiographic, and biochemical variables revealed a dominant pathological remodelling axis that distinguished WKY from SHRs. Saskatoon berry supplementation shifted SHRs toward an intermediate multivariate phenotype, supporting a coordinated improvement across structural and functional domains despite persistent hypertension. Together, these findings indicate that Saskatoon berry exerts blood pressure-independent cardioprotective effects that mitigate hypertensive LV hypertrophy and preserve systolic performance. Saskatoon berry may represent a promising functional food ingredient for attenuating cardiac remodelling in hypertension. Full article

Pregnancy involves profound metabolic, hormonal, and immunological adaptations essential for fetal development; however, disturbances may lead to complications such as preeclampsia (PE), pre-gestational diabetes, and gestational diabetes mellitus (GDM). These conditions are closely linked to oxidative stress, inflammation, endothelial dysfunction, impaired placentation, and metabolic dysregulation. Consequently, dietary strategies capable of modulating these pathways are of increasing interest. Edible and medicinal mushrooms are widely studied as functional food due to the content of bioactive compounds with antioxidant, anti-inflammatory, immunomodulatory, and metabolic regulatory effects. This review summarizes the nutritional composition of mushrooms and highlights key bioactive constituents with antioxidant and metabolic regulatory properties. Among them, ergothioneine has emerged as a key molecule due to its potent redox-buffering capacity and its potential involvement in the activation of the Nrf2 signaling pathway, a master regulator of cellular antioxidant defense. Through modulation of Nrf2-dependent gene expression, mushroom-derived compounds may contribute to improved cellular resilience against oxidative damage relevant to PE and GDM pathophysiology. Mushroom consumption has additionally been associated with improved glycemic control and enhanced antioxidant defenses in experimental and limited clinical studies, although evidence regarding the prevention or management of hypertensive and metabolic pregnancy complications remains insufficient. Although preclinical findings are promising, clinical evidence remains limited. Further well-designed prospective studies and randomized controlled trials are required to determine efficacy, safety, optimal intake, and active compounds responsible for these effects. Nevertheless, current evidence supports the biological plausibility that edible and medicinal mushrooms are promising dietary modulators of the ergothioneine–Nrf2 axis with potential relevance for maternal–fetal health. Full article

The inhibition of angiotensin-converting enzyme (ACE) to lower angiotensin is important in the treatment of hypertension (HT). ACE inhibitory activity is rarely documented in Thai traditional and indigenous medicine. Here, we evaluated the angiotensin I–converting enzyme inhibitory (ACEi) activity through bio-screening of selected medicinal plant species traditionally used for HT treatment by ethnic communities in northern Thailand, including Blumea balsamifera (L.) DC., Clerodendrum chinense (Osbeck) Mabb., Rotheca serrata (L.) Steane & Mabb., and Zingiber purpureum Roscoe. Using an in vitro assay, ethanolic extracts were evaluated for ACE inhibitory activity. Among the four extracts tested, the ethanolic leaf extract of Blumea balsamifera was the most effective by reducing ACE activity by 29, 36, and 64% at concentrations of 0.4, 2.0, and 10.0 mg/mL, respectively. The rhizome extract of Zingiber purpureum showed the second highest activity, with inhibition rates of 34%, 39%, and 40% at the corresponding concentrations. Cytotoxicity testing in HEK293T kidney cells was conducted to underscore the detectable toxicity under the tested conditions. Interestingly, intercultural and cross-cultural comparisons revealed a degree of agreement in the use of medicinal plants for hypertension treatment. Plant species traditionally used across multiple cultures tended to show higher levels of ACE inhibitory activity, suggesting their potential as candidates for the development of novel anti-hypertensive agents. To our knowledge, this is the first report describing the ACE inhibitory activity of medicinal plant species used for hypertension treatment by ethnic communities in northern Thailand. Full article

Hypertension is a major global public health challenge. Traditional antihypertensive drugs often cause side effects, which has prompted growing interest in natural antihypertensive agents. However, most existing antihypertensive peptides target single pathways, thereby constraining their effectiveness against hypertension’s complex mechanisms. In contrast, multi-target peptides modulate complex hypertension-related networks, offering enhanced blood pressure control and reduced resistance risks. This narrative review comprehensively summarizes the latest research progress on multi-target antihypertensive peptides, including their main food sources (animal, plant, and microorganism sources) and bioactive mechanisms. In addition, this review also describes the process of artificial intelligence (AI) and network pharmacology-driven multi-target antihypertensive peptide screening, and summarizes the machine learning (ML) models and activity prediction websites that have been applied to antihypertensive peptide screening. Finally, this review explores the challenges and future directions in multi-target antihypertensive peptide research, thereby providing a theoretical basis for the development of novel multi-target antihypertensive peptides. Full article

Moringa oleifera is rich in γ-aminobutyric acid (GABA), a functional non-protein amino acid with significant antihypertensive and neuroprotective activities. However, the key enzymes responsible for catalyzing the conversion of L-glutamate (L-Glu) to GABA—glutamate decarboxylases (GADs)—have not been functionally characterized in M. oleifera, which limits its metabolic engineering applications. In this study, the previously obtained MoGAD1 (PZ458702) and MoGAD2 (PZ458703) genes were heterologously expressed in Escherichia coli Rosetta (DE3) to produce recombinant proteins. SDS-PAGE and Western blot analyses showed that both MoGAD1 and MoGAD2 were solubly expressed at 20 °C and 37 °C. Their catalytic functions were verified via whole-cell biocatalysis, and high-performance liquid chromatography (HPLC) analysis confirmed that both MoGAD1 and MoGAD2 could convert L-Glu to GABA. The GABA yields of the engineered strains harboring MoGAD1 and MoGAD2 reached 3.67 ± 0.1833 g/L and 0.648 ± 0.002 g/L, with conversion rates of 61.2% and 10.8%, respectively. Both MoGAD1 and MoGAD2 exhibited favorable docking with PLP, with binding energies of −5.489 kcal/mol and −5.297 kcal/mol, respectively; they also showed good docking with L-Glu, with binding energies of −4.207 kcal/mol and −4.49 kcal/mol, respectively. This study provides the first experimental evidence for the activity of the MoGAD protein encoded by the GAD gene from M. oleifera, elucidates the molecular mechanism underlying GABA accumulation, and offers candidate genes for biotechnological production of GABA. Full article