Search Results (4,770)

Background/Objectives: Ischemic colitis, typically caused by thrombosis or reduced blood flow in the inferior mesenteric artery, is the most common ischemic lesion at the colorectal level. This case contributes to existing knowledge by highlighting the rare co-occurrence of a thrombosed aortic aneurysm and ischemic colitis, pointing to a direct vascular etiology rather than a multifactorial or idiopathic cause. Methods: A thorough electronic search was conducted on PubMed to identify risk factors and etiological determinants of ischemic colitis. Results: We present the case of a 70-year-old male with diffuse abdominal pain and multiple cardiac comorbidities. A CT scan revealed aeroenteritis, aerocolia, fusiform aneurysmal dilation of the abdominal aorta (18 cm long, 7.3 cm in diameter, from below the renal arteries to the bifurcation), parietal thrombosis, a circulating lumen of 2.7 cm, and inferior mesenteric artery thrombosis. Intraoperatively, necrosis was found in the upper rectum, sigmoid colon, descending colon, and the middle third of the left transverse colon, with clear demarcation between healthy and necrotic tissue. A subtotal proctocolectomy with transverse colostomy was performed. Conclusions: This case highlights ischemic colitis as a vascular disorder, urging broader differential diagnosis when common causes are unclear. Timely imaging, a multidisciplinary approach, and attention to vascular risks are key to identifying rare causes like aneurysmal thrombosis. While thrombosed abdominal aortic aneurysms can cause mesenteric ischemia, their link to ischemic and ulcerative colitis is unique, emphasizing the importance of accurate risk assessment in treatment planning. Full article

Preeclampsia is a hypertension condition of human pregnancy that poses a significant risk to pregnant women and their fetus. It complicates about 2–8% of human pregnancies worldwide and displays multifactorial pathogenesis, including increased placental oxidative stress because of disturbed utero-placental blood flow. Recent evidence suggests that increased oxidative stress promotes acceleration of the placental senescence which is implicated in the pathogenesis of preeclampsia. This review focuses on the mechanisms that lead to oxidative stress in preeclamptic patients and examines the role of oxidative stress-induced placental senescence in the pathogenesis of the disease. Full article

Sickle cell disease (SCD) is a monogenic blood disorder characterized by abnormal hemoglobin S production, which polymerizes under hypoxia conditions to produce chronic red blood cell hemolysis, widespread organ damage, and vasculopathy. As a result of vaso-occlusion and ischemia-reperfusion injury, individuals with SCD have recurrent pain episodes, infection, pulmonary disease, and fall victim to early death. Oxidative stress due to chronic hemolysis and the release of hemoglobin and free heme is a key driver of the clinical manifestations of SCD. The net result is the generation of reactive oxygen species that consume nitric oxide and overwhelm the antioxidant system due to a reduction in enzymes such as superoxide dismutase and glutathione peroxidase. The primary mechanism for handling cellular oxidative stress is the activation of antioxidant proteins by the transcription factor NRF2, a promising target for treatment development, given the significant role of oxidative stress in the clinical severity of SCD. In this review, we discuss the role of oxidative stress in health and the clinical complications of SCD, and the potential of NRF2 as a treatment target, offering hope for developing effective therapies for SCD. This task requires our collective dedication and focus. Full article

Secondary dilated cardiomyopathy (DCM) refers to left ventricular dilation and impaired systolic function arising from identifiable extrinsic causes, such as ischemia, hypertension, toxins, infections, systemic diseases, or metabolic disorders. Unlike primary DCM, which is predominantly genetic, secondary DCM represents a diverse spectrum of pathophysiological mechanisms linked to external insults on myocardial structure and function. The increasing prevalence of conditions such as alcohol use disorder, chemotherapy-induced cardiotoxicity, and viral myocarditis underscores the need for heightened awareness and early recognition of secondary DCM. A comprehensive analysis of clinical trial data and observational studies involving secondary dilative cardiomyopathy was conducted, with a focus on mortality, symptom relief, and major adverse events. A systematic literature review was performed using databases, including PubMed, Embase, and ClinicalTrials.gov, following PRISMA guidelines for study selection. Data were extracted on patient demographics, etiology of dilation, trial design, outcomes, and follow-up duration. Advances in diagnostic modalities have refined the ability to identify underlying causes of secondary DCM. For example, high-sensitivity troponin and cardiac magnetic resonance imaging are pivotal in diagnosing myocarditis and differentiating it from ischemic cardiomyopathy. Novel insights into toxin-induced cardiomyopathies, such as those related to anthracyclines and immune checkpoint inhibitors, have highlighted pathways of mitochondrial dysfunction and oxidative stress. Treatment strategies emphasize the management of the causing condition alongside standard heart failure therapies, including RAAS inhibitors and beta-blockers. Emerging therapies, such as myocardial recovery protocols in peripartum cardiomyopathy and immune-modulating treatments in myocarditis, are promising in reversing myocardial dysfunction. Secondary DCM encompasses a heterogeneous group of disorders that require a precise etiological diagnosis for effective management. Timely identification and treatment of the underlying cause, combined with optimized heart failure therapies, can significantly improve outcomes. Future research focuses on developing targeted therapies and exploring the role of biomarkers and precision medicine in tailoring treatment strategies for secondary DCM. Full article

Objective: The contralateral hippocampus, a critical region for cognitive function, is often overlooked in everyday clinical practice and stroke research. This study aimed to evaluate the effect of specific antiplatelet agents on the hippocampus (ipsilateral and contralateral) during the hyperacute phase of stroke. Materials and Methods: Twelve-week-old rats were randomly assigned to four groups, each containing six rats: a cilostazol group, an aspirin group, an aspirin plus cilostazol group, and a control group. Each substance was administered for four weeks. Permanent brain ischemia was induced over 2 h using intraluminal middle cerebral artery occlusion. A neurologic examination was conducted, followed by euthanasia and histological examination of the CA1 hippocampal region. The hematoxylin and eosin stain was used to assess the total number of intact neuronal cell bodies and pyknotic nuclei, an indicator of early irreversible neuronal injury. Results: In the ipsilateral hippocampus, monotherapy with either aspirin or cilostazol significantly reduced pyknotic nuclei compared with the control group (p = 0.0016 and p = 0.0165, respectively). However, combination therapy showed no significant difference from the controls (p = 0.2375). In the contralateral hippocampus, cilostazol monotherapy demonstrated significantly reduced pyknotic nuclei (p = 0.0098), whereas aspirin monotherapy and combination therapy did not (p = 0.1009 and p = 0.9999, respectively). A cumulative analysis of both hemispheres revealed that monotherapy with aspirin or cilostazol markedly reduced injury markers (p = 0.0002 and p = 0.0001, respectively), whereas combined therapy revealed no significant benefit (p = 0.1984). A neurological assessment indicated that the most severe deficits were in the combination therapy group. Conclusions: To the best of our knowledge, this is the first study to compare acute histopathological changes in the affected and unaffected hippocampus after a stroke in a rat model. Dual antiplatelet therapy resulted in worse outcomes (histopathological and neurological) than monotherapy. Full article

Objective: The benign nature of perimesencephalic subarachnoid hemorrhage (pmSAH) can be challenged by the occurrence of complications. Given the limited prognostic value of established clinical parameters for the development of complications in patients with pmSAH, this study evaluates the potential of volumetric hemorrhage quantification for risk assessment and the evaluation of the clinical outcome. Material and Methods: In this retrospective single-center study, we analyzed all consecutive patients diagnosed with pmSAH between 2010 and 2023 at a tertiary care academic medical center in Germany. The volumetric quantification of the hemorrhage in cm³ was performed using non-contrast CT imaging. The occurrence of clinical complications, including hydrocephalus, vasospasm, and delayed cerebral ischemia (DCI), were assessed. Clinical outcomes were determined by the Glasgow Outcome Scale (GOS) at discharge. Multivariable logistic regression models were used to assess the correlation between quantified hemorrhage volumes and the occurrence of complications and clinical outcomes (GOS) controlled for other variables such as age, sex, cardiovascular risk factors, clinical symptoms, and the modified Fisher scale. Results: A total of 82 patients (58.5% male, 54.8 ± 12.1 years) were enrolled. The median World Federation of Neurosurgical Societies (WFNS) score for all patients at admission was 1.0 (IQR 1.0–1.0). During the clinical course, hydrocephalus occurred in 29%, vasospasm in 14.6%, and DCI in 8.5% of all patients. Hemorrhage volume quantification was found to be the strongest independent predictor for hydrocephalus (OR 1.28; 95% CI 1.02–1.61; p = 0.032) and vasospasm (OR 1.25; 95% CI 1.07–1.46; p = 0.007) and showed a high predictive accuracy in ROC analyses (AUC = 0.77 and 0.76, respectively). Conversely, neither clinical parameters nor the modified Fisher scale were associated with these complications. A higher hemorrhage volume was also significantly correlated with a worse functional outcome (GOS; β = –0.07, CI: −0.12–−0.02, p = 0.021). Conclusions: In patients with pmSAH, the volumetric quantification of hemorrhage may be an adequate prognostic parameter regarding the occurrence of hydrocephalus and vasospasm. In addition, the quantitative assessment of hemorrhage volumes was strongly associated with clinical outcomes in these patients. Despite the generally benign nature of pmSAH, this imaging biomarker could improve individualized clinical management strategies and inform about the risk for the occurrence of complications. Full article

Acute surgical abdomen is characterized by intense, sudden abdominal pain due to intra-abdominal conditions requiring prompt surgical intervention. The coronavirus disease 2019 (COVID-19) pandemic has led to various complications related to the disease’s complex pathophysiological mechanisms, hence the hypothesis of COVID-19-induced acute abdominal surgical pathologies. The connection between acute surgical abdomen and COVID-19 involves two primary mechanisms. First, there is the presence of angiotensin-converting enzyme 2 (ACE2) receptors in multiple abdominal organs. This facilitates the cytokine storm through direct viral injury and inflammation. Second, the hypercoagulable state induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) increases the thrombotic risk within abdominal vessels, which can subsequently lead to ischemia. ACE2 receptors are notably expressed in the gastric, duodenal, and rectal epithelium, with SARS-CoV-2 viral RNA and nucleocapsid proteins detected in these tissues. The inflammatory response results in significant endothelial damage, activating coagulation pathways that cause monocellular infiltration, lymphocytic inflammation, and uncontrolled coagulation. These findings highlight the need for further research to clarify how COVID-19 leads to acute abdominal pathologies. Understanding these mechanisms is vital for improving clinical management and patient outcomes during future health crises and in the aftermath of the pandemic. Full article

Background: Acute bowel ischemia that develops secondarily to thrombotic occlusion of the superior mesenteric artery is a life-threatening abdominal emergency. Although an open surgical repair is still the main treatment modality for this pathology, percutaneous endovascular revascularization is currently recognized as an alternative therapeutic option. However, in some patients, endovascular repair of the occluded superior mesenteric artery is technically very challenging. Case description: We provide technical details of percutaneous endovascular revascularization of the superior mesenteric artery in a patient presenting with highly calcified plaques extending to the aortic wall, with an associated risk of the aortic wall rupturing after standard balloon angioplasty. The patient was managed using the lithotripsy-assisted angioplasty, in order to minimize the risk of aortic injury. Conclusion: During endovascular reconstruction of the superior mesenteric artery for acute bowel ischemia, on the one hand, a full revascularization of the ischemic bowel should be achieved. On the other hand, the procedure should not be too aggressive. In this technical note, we demonstrated that even very difficult cases can be successfully managed endovascularly, if a tailored approach is used and proper endovascular devices are applied. Full article

Ischemic stroke is a leading cause of death and disability worldwide. Currently, there is an unmet clinical need for pharmacological treatments that can improve ischemic stroke outcomes. In this study, we investigated the role of brain peroxisome proliferator-activated receptor alpha (PPARα) in ischemic stroke pathophysiology. We used a well-established model of cerebral ischemia in PPARα transgenic mice and conducted the RNA sequencing (RNA-seq) of mouse stroke brains harvested 48 h post-middle cerebral artery occlusion (MCAO). PPARα knockout (KO) increased brain infarct size following stroke, indicating a protective role of PPARα in brain ischemia. Our RNA-seq analysis showed that PPARα KO altered the expression of genes in mouse brains with known roles in ischemic stroke pathophysiology. We also identified many other differentially expressed genes (DEGs) upon the loss of PPARα that correlated with increased infarct size in our stroke model. Gene set enrichment analysis (GSEA) and Gene Ontology (GO) analysis revealed the upregulation of gene signatures for the positive regulation of leukocyte proliferation, apoptotic processes, acute-phase response, and cellular component disassembly in mouse stroke brains with PPARα KO. In addition, pathway analysis of our RNA-seq data revealed that TNFα signaling, IL6/STAT3 signaling, and epithelial–mesenchymal transition (EMT) gene signatures were increased in PPARα KO stroke brains. Our study highlights PPARα as an attractive drug target for ischemic stroke due to its transcriptional regulation of inflammation-, apoptosis-, and EMT-related genes in brain tissue following ischemia. Full article

Retinal ischemic disorders present significant threats to vision, characterized by inadequate blood supply oxygen–glucose deprivation (OGD), oxidative stress, and cellular injury, often resulting in irreversible injury. Catalpol, an iridoid glycoside derived from Rehmannia glutinosa, has demonstrated antioxidative and neuroprotective effects. This study aimed at investigating the protective effects and mechanisms of catalpol against oxidative stress or OGD in vitro and retinal ischemia in vivo, focusing on the modulation of key biomarkers of retinal ischemia, including HIF-1α, vascular endothelial growth factor (VEGF), angiopoietin-2, MCP-1, and the Wnt/β-catenin pathway. Cellular viability was assessed using retinal ganglion cell-5 (RGC-5) cells cultured in DMEM; a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed. H₂O₂ (1 mM)/OGD was utilized. Vehicle or different catalpol concentrations were administered 15 min before the ischemic-like insults. The Wistar rat eyes’ intraocular pressure was increased to 120 mmHg for 60 min to induce retinal ischemia. Intravitreous injections of catalpol (0.5 or 0.25 mM), Wnt inhibitor DKK1 (1 μg/4 μL), anti-VEGF Lucentis (40 μg/4 μL), or anti-VEGF Eylea (160 μg/4 μL) were administered to the rats’ eyes 15 min before or after retinal ischemia. Electroretinogram (ERG), fluorogold retrograde labeling RGC, Western blotting, ELISA, RT-PCR, and TUNEL were utilized. In vitro, both H₂O₂ and OGD models significantly (p < 0.001/p < 0.001; H₂O₂ and OGD) induced oxidative stress/ischemic-like insults, decreasing RGC-5 cell viability (from 100% to 55.14 ± 2.19%/60.84 ± 4.57%). These injuries were insignificantly (53.85 ± 1.28% at 0.25 mM)/(63.46 ± 3.30% at 0.25 mM) and significantly (p = 0.003/p = 0.012; 64.15 ± 2.41%/77.63 ± 8.59% at 0.5 mM) altered by the pre-administration of catalpol, indicating a possible antioxidative and anti-ischemic effect of 0.5 mM catalpol. In vivo, catalpol had less effect at 0.25 mM for ERG amplitude ratio (median [Q1, Q3] 14.75% [12.64%, 20.48%]) and RGC viability (mean ± SE 63.74 ± 5.13%), whereas (p < 0.05 and p < 0.05) at 0.5 mM ERG’s ratio (35.43% [24.35%, 43.08%]) and RGC’s density (74.34 ± 5.10%) blunted the ischemia-associated significant (p < 0.05 and p < 0.01) reduction in ERG b-wave amplitude (6.89% [4.24%, 10.40%]) and RGC cell viability (45.64 ± 3.02%). Catalpol 0.5 mM also significantly protected against retinal ischemia supported by the increased amplitude ratio of ERG a-wave and oscillatory potential, along with recovering a delayed a-/b-wave response time ratio. When contrasted with DKK1 or Lucentis, catalpol exhibited similar protective effects against retinal ischemia via significantly (p < 0.05) blunting the ischemia-induced overexpression of β-catenin, VEGF, or angiopoietin-2. Moreover, ischemia-associated significant increases in apoptotic cells in the inner retina, inflammatory biomarker MCP-1, and ischemic indicator HIF-1α were significantly nullified by catalpol. Catalpol demonstrated antiapoptotic, anti-inflammatory, anti-ischemic (in vivo retinal ischemia or in vitro OGD), and antioxidative (in vitro) properties, counteracting retinal ischemia via suppressing upstream Wnt/β-catenin and inhibiting downstream HIF-1α, VEGF, and angiopoietin-2, together with its decreasing TUNEL apoptotic cell number and inflammatory MCP-1 concentration. Full article

Hypertension-induced cardiac remodeling is a complex process driven by interconnected molecular and cellular mechanisms that culminate in hypertensive myocardium, characterized by ventricular hypertrophy, fibrosis, impaired angiogenesis, and myocardial dysfunction. This review discusses the histomorphometric changes in capillary density, fibrosis, and mast cells in the hypertensive myocardium and delves into the roles of key regulatory systems, including the apelinergic system, vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathways, and nitric oxide (NO)/nitric oxide synthase (NOS) signaling in the pathogenesis of hypertensive heart disease (HHD). Capillary rarefaction, a hallmark of HHD, contributes to myocardial ischemia and fibrosis, underscoring the importance of maintaining vascular integrity. Targeting capillary density (CD) through antihypertensive therapy or angiogenic interventions could significantly improve cardiac outcomes. Myocardial fibrosis, mediated by excessive collagen deposition and influenced by fibroblast growth factor-2 (FGF-2) and transforming growth factor-beta (TGF-β), plays a pivotal role in the structural remodeling of hypertensive myocardium. While renin–angiotensin–aldosterone system (RAAS) inhibitors show anti-fibrotic effects, more targeted therapies are needed to address fibrosis directly. Mast cells, though less studied in humans, emerge as critical regulators of cardiac remodeling through their release of pro-fibrotic mediators such as histamine, tryptase, and FGF-2. The apelinergic system emerges as a promising therapeutic target due to its vasodilatory, anti-fibrotic, and cardioprotective properties. The system counteracts the deleterious effects of the RAAS and has demonstrated efficacy in preclinical models of hypertension-induced cardiac damage. Despite its potential, human studies on apelin analogs remain limited, warranting further exploration to evaluate their clinical utility. VEGF signaling plays a dual role, facilitating angiogenesis and compensatory remodeling during the early stages of arterial hypertension (AH) but contributing to maladaptive changes when dysregulated. Modulating VEGF signaling through exercise or pharmacological interventions has shown promise in improving CD and mitigating hypertensive cardiac damage. However, VEGF inhibitors, commonly used in oncology, can exacerbate AH and endothelial dysfunction, highlighting the need for therapeutic caution. The NO/NOS pathway is essential for vascular homeostasis and the prevention of oxidative stress. Dysregulation of this pathway, particularly endothelial NOS (eNOS) uncoupling and inducible NOS (iNOS) overexpression, leads to endothelial dysfunction and nitrosative stress in hypertensive myocardium. Strategies to restore NO bioavailability, such as tetrahydrobiopterin (BH₄) supplementation and antioxidants, hold potential for therapeutic application but require further validation. Future studies should adopt a multidisciplinary approach to integrate molecular insights with clinical applications, paving the way for more personalized and effective treatments for HHD. Addressing these challenges will not only enhance the understanding of hypertensive myocardium but also improve patient outcomes and quality of life. Full article

This research proposes to systematically investigate the cardioprotective mechanisms of Pericarpium Trichosanthis injection (PTI) against acute myocardial ischemia through an integrated approach combining ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) constituent profiling, UNIFI database-assisted component identification, network pharmacology-guided target prediction, molecular docking verification, and in vivo experimental validation. The multimodal methodology is designed to comprehensively uncover the therapeutic benefits and molecular pathways underlying this traditional Chinese medicine formulation. Methods: UPLC-Q-TOF/MS and the UNIFI database were used in conjunction with a literature review to screen and validate the absorbed components of PTI. Using network pharmacology, we constructed protein-protein interaction (PPI) networks for pinpointing prospective therapeutic targets. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify potential signaling pathways. In vivo experiments were conducted to investigate the mechanisms by which PTI ameliorated isoproterenol-induced myocardial injury in rats. All animal experiments have adhered to ARRIVE guidelines. Results: UPLC-Q-TOF/MS revealed 11 core active components in PTI. Network pharmacology prioritization identified pseudoaspidin, ciryneol C, cynanoside M, daurinol, and n-butyl-β-D-fructopyranoside as central bioactive constituents within the compound-target interaction network. Topological analysis of the protein interactome highlighted AKT1, EGFR, MMP9, SRC, PTGS2, STAT3, BCL2, CASP3, and MAPK3 as the most interconnected nodes with the highest betweenness centrality. Pathway enrichment analysis established the PI3K/Akt signaling cascade as the principal mechanistic route for PTI’s cardioprotective effects. Molecular docking simulations demonstrated high-affinity interactions between characteristic components (e.g., cynanoside M, darutigenol) and pivotal targets including PTGS2, MAPK3, CASP3, and BCL2. In vivo investigations showed PTI treatment markedly attenuated myocardial tissue degeneration and collagen deposition (p < 0.05), normalized electrocardiographic ST-segment deviations, and suppressed pro-inflammatory cytokine production (IL-6, TNF-α). The formulation concurrently reduced circulating levels of cardiac injury indicators (LDH, cTnI) and oxidative stress parameters (ROS, MDA), Regarding apoptosis regulation, PTI reduced Bax, caspase-3, and caspase-9, while elevating Bcl-2 (p < 0.05), effectively inhibiting myocardial cell apoptosis with all therapeutic outcomes reaching statistical significance. These findings highlight PTI’s protective effects against myocardial injury through multi-target modulation of inflammation, oxidation, and apoptosis. Conclusions: PTI exerts its therapeutic effects in treating acute myocardial ischemia by regulating and suppressing inflammatory responses, and inhibiting cardiomyocyte apoptosis. Full article

Atrial fibrillation (Afib) recurrence after catheter ablation (CA) remains a significant clinical challenge, driven by a complex and dynamic interplay of structural, electrical, and autonomic mechanisms. While pulmonary vein isolation (PVI) is the cornerstone of CA, recurrence rates remain substantial, highlighting the need to understand the evolving pathophysiology beyond PV reconnection. Post-ablation changes, including inflammation, edema, oxidative stress, and ischemia, create a transient proarrhythmic state that may contribute to early recurrence. Over time, atrial remodeling, fibrosis, and residual autonomic activity further sustain arrhythmogenicity. Additionally, epicardial adipose tissue promotes atrial myopathy, accelerating disease progression, particularly in patients with risk factors such as older age, female sex, obesity, hypertension, obstructive sleep apnea, and heart failure. The multifactorial nature of Afib recurrence underscores the limitations of a “one-size-fits-all” ablation strategy. Instead, a patient-specific approach integrating advanced mapping techniques, multimodal imaging, and computational modeling is essential. Artificial intelligence (AI) and digital twin models hold promise for predicting recurrence by simulating individualized disease progression and optimizing ablation strategies. However, challenges remain regarding the standardization and validation of these novel approaches. A deeper understanding of the dynamic interconnections between the mechanisms driving recurrence is crucial for improving long-term CA outcomes. This review explores the evolving nature of Afib recurrence, emphasizing the need for a precision medicine approach that accounts for the continuous interaction of pathophysiological processes in order to refine patient selection, ablation strategies, and post-procedural management. Full article

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition that results from intracranial aneurysm rupture, leading to the accumulation of blood between the arachnoid and pia mater. The blood breakdown products and damage-associated molecule patterns (DAMPs), which are released as a result of vascular and cellular compromise following aneurysm rupture, elicit local endothelial reactions leading to the narrowing of cerebral arteries and ischemia. In addition, vascular inflammation, characterized by activated endothelial cells, perpetuates disruption of the neurovascular unit and the blood–brain barrier. The uncertain prognosis of aSAH patients contributes to the necessity of a fluid biomarker that can serve as a valuable adjunct to radiological and clinical evaluation. Limited studies have investigated vascular inflammation and angiogenic protein expression following aSAH. Reliable markers of the vascular inflammatory and angiogenic response associated with aSAH may allow for the earlier detection of patients at risk for complications and aid in the identification of novel pharmacologic targets. We investigated whether vascular inflammatory and angiogenesis signaling proteins may serve as potential biomarkers of aSAH. Serum and cerebrospinal fluid (CSF) from fifteen aSAH subjects and healthy age-matched controls as well as hydrocephalus (CSF) no-aneurysm controls were evaluated for levels of vascular inflammatory and angiogenesis proteins. Protein measurement was carried out using electrochemiluminescence. The area under the curve (AUC) was calculated using receiver operating characteristics (ROC) to obtain information on biomarker reliability, specificity, sensitivity, cut-off points, and likelihood ratio. In addition, patients were grouped by Glasgow Outcome Score—Extended at 3 months post-injury to determine the correlation between vascular inflammatory protein levels and clinical outcome measures. aSAH subjects demonstrated elevated vascular inflammatory protein levels in serum and CSF when compared to controls. Certain vascular injury and angiogenic proteins were found to be promising biomarkers of inflammatory response in aSAH in the CSF and serum. In particular, elevated levels of serum amyloid-alpha (SAA) were found to be correlated with unfavorable outcomes following aSAH. Determination of these protein levels in CSF and serum in aSAH may be utilized as reliable biomarkers of inflammation in aSAH and used clinically to monitor patient outcomes. Full article

Although various factors contribute to the transition from acute kidney injury (AKI) to chronic kidney disease (CKD), no clinically effective pharmacological treatment has been established. We investigated whether chymase inhibition is effective in preventing renal fibrosis, a key process in the transition from AKI to CKD. Male BALB/c mice were subjected to unilateral ischemia-reperfusion (I/R) injury, and TY-51469, a chymase-specific inhibitor, was administered intraperitoneally at a dose of 10 mg/kg/day for 6 weeks. The 45 min ischemic period followed by 6 weeks of reperfusion resulted in severe renal atrophy. Renal fibrosis was particularly pronounced in the transition region between the cortex and medulla in placebo-treated mice. The expression of mouse mast cell protease 4 (MMCP-4, a mouse chymase) mRNA, the number of chymase-positive mast cells, and fibrosis-related factors, such as transforming growth factor (TGF)-β1 and collagen I, were all significantly increased in I/R-injured kidneys. However, treatment with TY-51469 significantly suppressed fibrosis formation, along with the inhibition of renal chymase and TGF-β1 expression. These findings suggest that chymase inhibition may be a potential therapeutic strategy for preventing the transition from AKI to CKD by reducing fibrosis. Full article