This study presents a supervised machine learning approach using a Random Forest classifier to detect ischemia-reperfusion injury (IRI) in kidney tissue based on intravital two-photon microscopy data. A rodent model of unilateral renal IRI was used, with 30 min of pedicle occlusion followed by 15 min of reperfusion. Continuous imaging captured nuclear (Hoechst 33342), vascular (FITC-dextran), and mitochondrial (TMRM) changes in real time. From extracted video frames, 2000 manually segmented regions of interest (ROIs), 1000 control and 1000 injured segments, were analyzed using texture analysis. Five textural features were used as input: angular second moment (ASM) and inverse difference moment (IDM) from gray-level co-occurrence matrix (GLCM); short run emphasis (SRE) and long run emphasis (LRE) from run length matrix (RLM); and HH wavelet coefficient energy (EnHH) from discrete wavelet transform (DWT). All showed significant differences (p < 0.001) between injured and control tissue. The Random Forest model achieved 79.8% accuracy, a macro F1-score of 0.79, a Matthews Correlation Coefficient of 0.5959, and an ROC AUC of 0.83. These findings highlight the potential of AI-based texture analysis to detect early nuclear and vascular alterations during IRI. Future work should expand datasets, include 3D analyses, and incorporate multimodal imaging for greater generalizability.

Although body weight (BW) and waist circumference (WC) reduction are key goals of Japan's Specific Health Guidance program, limited evidence exists linking these reductions to a lower incidence of hypertension. This study aimed to evaluate the association between changes in BW and WC and the subsequent development of hypertension among men in a nationwide population. We retrospectively analyzed 23,109 men aged 40-64 years who required intensive health guidance and had no prior history of hypertension, using a nationwide database (DeSC Healthcare, Tokyo, Japan) from April 2014 to August 2023. One-year changes in BW and WC were examined for their association with incident hypertension using multivariable Cox regression and cubic spline analyses. During a mean follow-up of 1381 ± 789 days, 4162 men (18.0%) developed hypertension. Greater reductions in BW and WC were associated with a progressively lower risk of hypertension. In multivariable Cox models, BW reductions of ≤ -3.0 kg, -2.9 to -2.0 kg, and -1.9 to -1.0 kg were significantly associated with reduced hypertension risk (HR: 0.74 [95% CI: 0.67-0.82], 0.85 [0.76-0.96], and 0.89 [0.81-0.99], respectively). WC reductions of ≤ -3.0 cm and -2.9 to -2.0 cm were also significantly associated with reduced risk (HR: 0.80 [0.73-0.88] and 0.81 [0.72-0.92], respectively). Cubic spline analyses confirmed a monotonic decrease in hypertension risk with increasing BW and WC reduction. Among men eligible for Specific Health Guidance, one-year reductions in BW and WC were significantly associated with a lower risk of developing hypertension.

Ischemic stroke (IS) is an acute neurological disorder causing brain dysfunction, with high mortality and disability. PANoptosis is a synchronized sort of regulated cell demise that combines the characteristics of pyroptosis, apoptosis, and necroptosis. However, its role in ischemic stroke remains unclear. We downloaded the ischemic stroke-related microarray dataset GSE58294 from the Gene Expression Omnibus (GEO) database and identified Differentially expressed PANoptosis-related genes (DE-PRGs). We utilized three algorithms to identify diagnostic DE-PRGs, constructed a nomogram for diagnostic modeling, and evaluated their diagnostic performance with receiver operating characteristic (ROC) analysis. Additionally, we develop interaction networks linking genes with miRNAs, transcription factors, and drugs. We also analyzed gene expression in different cell subgroups using the GSE174574 single-cell dataset. We applied consensus clustering to classify stroke samples into subtypes and compared immune microenvironment differences. Ultimately, we verified the gene expression patterns of candidate markers through the MCAO model. We pinpointed seven diagnostic DE-PRGs, with CASP1, PIK3R5, AVEN, and PSMC3 showing significant protein expression differences. Single-cell transcriptome analysis revealed the link between stroke and immune cells. Furthermore, consensus clustering revealed two clusters with unique immune infiltration patterns and functional characteristics. Our study may provide new theoretical insights for the early diagnosis and targeted therapy of IS and offer support for the clinical application of PANoptosis in IS.

Obesity is a recognized risk factor for cardiovascular morbidity and mortality, however its impact on survival following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) remains controversial. Therefore, the aim of this study was to evaluate the feasibility of a preclinical model of CA/CPR in obese rats as well as 72-hour (h) survival, and investigate the effect of obesity on myocardial dysfunction post-CA/CPR. Rats were subjected to 6 min of untreated ventricular fibrillation and to 6 min of CPR. Hemodynamic parameters were continuously recorded up to 4 h, serial blood samples were collected and echocardiography was performed at 2 and 4 h after resuscitation. Rats were sacrificed 72 and 4 h after resuscitation. After CA, no obese rats survived up to 72 h compared to controls whereas each rat developed marked post- return of spontaneous circulation hemodynamic impairment during the 4 h observation; obese rats showed an impairment in diastolic function as well as a significant increase in troponin T plasma concentration compared to controls. This could support that obesity negatively impacts survival, hemodynamic stability and left ventricular function after CA.

Ischaemic heart disease remains a leading cause of mortality worldwide, highlighting the need for new agents that protect vascular function. Tectorigenin, a plant-derived isoflavone, is known for its anti-inflammatory and antioxidant properties, but its direct effects on vascular tone have not been clearly explored. This study investigated the vasorelaxant actions of tectorigenin in endothelium-denuded porcine coronary arteries and examined the mechanisms involved. Using isolated artery rings pre-contracted with a thromboxane A₂ analogue, we found that tectorigenin induced concentration-dependent relaxation with an EC₅₀ of approximately 11 µM. Pharmacological inhibition experiments revealed that relaxation at 10-30 µM was significantly reduced by oestrogen receptor antagonists and by 4-aminopyridine, a blocker of voltage-gated potassium channels, and was completely abolished under high-potassium conditions. In contrast, inhibitors targeting neural conduction, nitric oxide synthase, cyclic nucleotide pathways, and other potassium channels had no significant impact. Immunohistochemistry and qPCR analyses indicated predominant ERα expression in the coronary arteries. These findings are consistent with contributions from oestrogen receptors (with ERα predominance) and 4-AP-sensitive Kv channels to the relaxant response; a direct ER-Kv coupling was not established in this ex vivo model. This is the first study to characterise the vascular pharmacology of tectorigenin in a large-animal coronary model. Further in vivo investigations are warranted to assess its potential in managing cardiovascular diseases.

Despite decades of studies into the mechanisms underlying acute kidney injury (AKI), the effective clinical therapies are still limited. Here we report that the development of AKI was attenuated by conditional knockout of phosphoglycerate kinase 1 (PGK1) in renal tubular epithelial cells (RTECs) and aggravated by specific overexpression of PGK1 and administration of 3-phosphoglycerate (3-PG) in male mice. PGK1 interacted with pyruvate kinase M2 (PKM2), inducing PKM2 phosphorylation, promoting the formation of the PKM2 dimer and the subsequent nuclear translocation of PKM2. In the nucleus, the interaction of PKM2 with Pknox1 potentiated the enrichment of Pknox1 within ALOX12 promoters, which resulted in ALOX12-mediated ferroptosis in RTECs. Our drug screening experiments identified L7DG as a potential PGK1 inhibitor which exhibited protective effects against ischemic/reperfusion (I/R)-induced renal injury. Overall, we establish that genetic and pharmacological inhibition of PGK1 might be proposed as an avenue for managing AKI.

Post-cardiac injury syndrome (PCIS) refers to a group of inflammatory pericardial syndromes that arise after cardiac injury, encompassing post-myocardial infarction syndrome, post-pericardiotomy syndrome, and post-traumatic pericarditis. PCIS has evolved significantly over recent years, transitioning from a rare post-myocardial infarction syndrome to a more common phenomenon stemming from the rise of both surgical and transcatheter cardiac procedures. The increasing prevalence of these procedures makes understanding and managing PCIS an important clinical consideration. Additionally, in rare instances of post-MI pericarditis, balancing the reduction of inflammation while maintaining structural cardiac integrity for healing presents unique therapeutic challenges. In this review, we aim to provide a comprehensive overview of PCIS, focusing on its most common manifestations, key imaging modalities for diagnosis, and novel therapeutic strategies.

Worsening heart failure is a common cause of morbidity and mortality among patients worldwide. It is important to recognize changes in a patient's clinical care to understand the risk to their cardiovascular health and overall well-being. Events that define worsening heart failure include hospital admission for heart failure, emergency department visit for heart failure, outpatient intravenous diuretic therapy, escalation of outpatient oral diuretic therapy, and worsening symptoms despite appropriate medical therapy. Optimization of heart failure guideline-directed medical therapy during a worsening heart failure episode has been shown to improve patient survival, reduce hospitalization, and improve patient-reported outcomes.

Pharmacotherapy for heart failure (HF) with reduced ejection fraction (HFrEF) is the foundation of management. The basis of pharmacotherapy for HFrEF includes 4 pillars: beta-blockers, renin angiotensin aldosterone system modulators, mineralocorticoid receptor antagonists, and sodium glucose cotransporter 2 inhibitors. These drug classes collectively reduce mortality, hospitalizations, and can improve functional and clinical status. Additional pharmacotherapy with loop diuretics and sometimes addition of thiazide diuretics at the core can reduce HF symptoms. Contemporary data from recent randomized clinical trials have established a new foundation of successful management of patients with preserved ejection fraction HF.