Hypertension is a major contributor to cardiovascular morbidity and mortality, largely driven by oxidative stress, mitochondrial dysfunction, endothelial injury, and chronic vascular inflammation. Emerging evidence suggests that targeting vascular bioenergetics may provide complementary therapeutic strategies beyond conventional antihypertensive drugs. This review explores the mitochondrial protective mechanisms of Piper retrofractum and its major bioactive compounds in the context of hypertension and oxidative vascular injury. The phytochemical profile of P. retrofractum, particularly piperine, piplartine, pipernonaline, and retrofractamides, demonstrates significant antioxidant, anti-inflammatory, and metabolic regulatory activities. Mechanistically, these compounds may attenuate mitochondrial reactive oxygen species (mtROS), restore endothelial nitric oxide synthase (eNOS) coupling, activate AMPK-SIRT1-PGC-1α signaling, induce Nrf2-HO-1 antioxidant pathways, and modulate mitochondrial dynamics and mitophagy. Collectively, these effects contribute to improved endothelial function, reduced vascular remodeling, suppression of inflammatory cascades, and enhanced mitochondrial resilience. In addition, emerging omics technologies, network pharmacology, and AI-assisted nutraceutical discovery offer new opportunities to elucidate multitarget mechanisms and optimize P. retrofractum-based interventions. Despite promising preclinical evidence, important limitations remain, including insufficient clinical studies, limited mitochondrial-specific investigations, and challenges related to bioavailability and standardization. Overall, P. retrofractum represents a promising mitochondria-centered nutraceutical candidate for hypertension management and vascular protection, warranting further translational and clinical investigation.

Staphylococcus aureus (S. aureus) is a leading cause of bacteraemia and infective endocarditis worldwide, posing significant public health challenges in resource-limited low- and middle-income countries (LMICs). However, whether specific genomic factors influence the development of S. aureus infective endocarditis (SAIE) during S. aureus bacteraemia (SAB) remains unclear. Thus, the study aimed to determine whether clinical SAIE isolates were genomically distinguishable from SAB isolates originating from public hospitals in Gauteng, South Africa. Seventy-seven (54 SAB, 23 SAIE) bloodstream isolates were characterised to assess antimicrobial susceptibility (VITEK®2 system), biofilm formation (crystal violet assay), virulence genes (multiplex-polymerase chain reactions) and genetic relatedness (pulsed-field gel electrophoresis), while 12 representative isolates underwent whole-genome sequencing. A higher SAIE (29.9%) prevalence than previously reported in South Africa was observed, with cases linked to young male persons who inject drugs (P < 0.01). While the SAB and SAIE groups did not differ in virulence profiles, SAB isolates demonstrated higher resistance rates to gentamicin and clindamycin than SAIE isolates (P < 0.05). The endemic Panton-Valentine leukocidin-positive sequence type (ST) 152, clonal complex (CC) 152 lineage predominated in SAIE isolates, while the pandemic CC8, encompassing ST239 and ST612, was exclusive to SAB isolates. Overall, SAB and SAIE isolates were not clearly distinguished by the markers assessed, suggesting that SAIE development may reflect the combined effects of bacterial traits, host susceptibility and exposure-related risk factors, rather than a distinct SAIE-specific genomic profile. These findings highlight the need for continued genomic surveillance of circulating S. aureus lineages to inform targeted infection-control strategies.

Tachycardia-induced cardiomyopathy secondary to persistent tachycardia in children is a distinct form of cardiomyopathy caused by sustained or frequent tachyarrhythmias. It is characterized by cardiac enlargement, impaired cardiac function, and heart failure and is clinically reversible with early and standardized treatment. Herein, we report a challenging pediatric case presenting with recurrent intermittent dyspnea and palpitations for 1 year. The final diagnoses were as follows: (a) paroxysmal atrial tachycardia and (b) tachycardia-induced cardiomyopathy. Under the guidance of a three-dimensional electroanatomical mapping system, an intracardiac electrophysiological study accurately localized the focal atrial tachycardia to the posterior margin of the right upper pulmonary vein, followed by successful radiofrequency ablation. The patient's clinical symptoms improved significantly postoperatively, and the patient was discharged uneventfully. During the 8-month follow-up period, no recurrence of atrial tachycardia was documented. Follow-up echocardiography confirmed normalization of cardiac dimensions and function.

Myeloperoxidase (MPO), a key enzyme involved in neutrophil extracellular trap formation and other inflammatory processes, has emerged as an attractive therapeutic target for cardiovascular, central nervous system, respiratory, and autoimmune diseases. To date, four irreversible MPO inhibitors have entered clinical trials; however, none have reached the market, highlighting the challenges of MPO drug discovery.

This review provides an overview of MPO biology, its pathological roles in inflammatory diseases, and recent advances in MPO drug discovery. It then systematically summarizes patent literature published between 2020 and 2026, identified through Espacenet, Google Patents, and SciFinder, comprehensively covering the structural optimization and pharmacological characterization of emerging MPO inhibitors, including small molecules, peptides, and antibodies.

Patent analysis indicates that MPO drug discovery remains heavily dependent on legacy thioxanthine/deazathioxanthine scaffolds. Current efforts are primarily focused on overcoming historical liabilities through improving target selectivity and pharmacokinetic properties. In parallel, non-thioxanthine chemotypes are emerging, although most still exhibit suboptimal potency and therefore require further optimization. The development of dual- or multi-target MPO inhibitors may represent a promising strategy for addressing complex inflammatory networks.

Chronic kidney disease (CKD) represents a significant public health problem. Patients with CKD have high morbidity and mortality, mainly due to cardiovascular diseases. As CKD progresses, impaired renal clearance leads to the progressive accumulation of uremic toxins, culminating in deleterious effects on multiple organ systems. Uremic toxins contribute to cardiovascular disease by inducing inflammation, oxidative stress, and endothelial barrier dysfunction, thereby promoting atherosclerotic processes. They are also potentially implicated in neurological impairment, bone disorders, and sarcopenia. Some uremic toxins originate from dietary components and gut microbiota metabolism, which are key mechanisms and pathways in uremic toxicity. Current dialysis therapies only partially mitigate uremic toxicity, highlighting the need for strategies that reduce uremic toxin generation as well as more efficient dialysis modalities. Given the importance of uremic toxins in CKD progression, this review provides a comprehensive overview of uremic toxicity, focusing on its pathophysiological mechanisms, its relationship with the gut microbiota, and emerging interventions to mitigate its deleterious effects.

Animal venoms are complex biochemical systems composed of proteins, peptides, and small molecules with bioactivity. Traditionally regarded as toxic agents, venom components are increasingly recognized as valuable molecular libraries that can modulate cellular processes in human disease pathophysiology. This review highlights the translational potential of venom-derived molecules, with emphasis on clinically approved venom-derived drugs such as captopril, while also discussing their therapeutic potential for diseases such as cancer, autoimmunity, cardiovascular diseases, chronic pain, neuropsychiatric disorders, and infectious diseases. Special emphasis is given to the mechanisms by which these toxins modulate ion channels, enzymes, and receptor systems. Recent advances in venomics, harnessing proteomics, transcriptomics, and high-throughput screening, are also discussed, which can accelerate the clinical translation of venom-derived therapeutics. Key challenges related to assessing the immunogenicity of the venom-derived compounds, bioavailability, and safety have also been addressed alongside emerging strategies to overcome them. Collectively, these advances can provide a logical framework for developing novel therapeutics, bridging the gap between toxinology and drug discovery.

Lipoproteins are molecules composed of phospholipids and apolipoproteins that transport triacylglycerol and cholesterol in blood and are implicated in the development of many diseases.

In this study, we fill a knowledge gap by precisely characterizing the apolipoprotein profile (with Bio-Plex Human Apolipoprotein Assay) in three metabolically separate groups of individuals (lean individuals and obese individuals without and with metabolic syndrome) and at four distinct time points (0, 3, 6, and 12 months post bariatric surgery).

Obese patients had a higher baseline ApoB/ApoA1 ratio, which returned to the reference level over the follow-up period. The above is of clinical importance, as the ratio is a predictor of adverse cardiovascular events common in obese subjects. Interestingly, plasma concentrations of most of the investigated apolipoproteins appeared to be relatively stable at the onset of the experiment, with changes observed later in time. We detected significant drops in the levels of ApoC3, ApoD, and ApoH that occurred as early as three months post intervention. On the other hand, the levels of ApoA2, ApoE, and ApoJ increased with time. Of the above, ApoE is known to be involved in the removal of TAGs and cholesterol from the blood. Conversely, ApoJ appears to be one of the determinants of the tissues' responsiveness to insulin. Thus, it may be an indicator of the reduced insulin resistance observed a few months after the surgery.

Overall, the investigated proteins have a documented role in the development and progression of vascular pathologies. Hence, our results may be interpreted as a sign of improved cardiovascular fitness of our patients.

Background/Objectives: Anthracycline-induced cardiotoxicity remains a major challenge in cancer treatment, and researchers are showing interest in artificial intelligence (AI) to improve the prediction and detection of cancer therapy-related cardiac dysfunction (CTRCD). Current surveillance strategies rely mainly on left ventricular ejection fraction and, more recently, global longitudinal strain. Methods: The present study was designed to evaluate cardiac performance in a rat model of doxorubicin-induced cardiotoxicity and empagliflozin-mediated cardioprotection using a machine learning-based analytical framework. Eighteen adult male Sprague-Dawley rats were assigned to five experimental groups. We aimed to quantify ventricular wall dynamics and contractility using an advanced image-processing and object-detection model that has not been previously used to distinguish normal from impaired cardiac kinetics. During real-time recording, simultaneous electrocardiogram monitoring was performed, enabling direct correlation between deep learning-based ventricular wall motion metrics and cardiac electrical activity. The cardioprotective effects of empagliflozin were further validated by immunofluorescence staining (cTnI, vimentin, α-SMA, and Cx43) of rat cardiomyocytes and paraffin-embedded cardiac tissue, demonstrating attenuation of cellular injury and structural remodeling. Results: The integrated analysis of cardiac kinetic patterns derived via machine learning distinguishes not only extreme cardiotoxicity, but also tracks a graded pattern consistent with ECG-derived severity and treatment-related functional preservation. These findings indicate that the algorithm captures the gradient of empagliflozin's cardioprotective effect within this internally validated preclinical setting. Additionally, immunofluorescence results validated the benefits of SGLT2 inhibition on myocardial integrity. Conclusions: The novelty of the present work lies at the intersection of advanced cardiac kinetic analysis using AI, preclinical modeling, and SGLT2-mediated cardioprotection in cardio-oncology.

Spinal dural arteriovenous fistulas (sDAVFs) are the most common spinal vascular malformation and a treatable cause of progressive myelopathy, yet diagnosis and optimal management remain challenging. This study presents a nine-year institutional experience using a multidisciplinary treatment algorithm that prioritizes endovascular embolization, with surgery reserved for unsuccessful or contraindicated cases.

We retrospectively analyzed 15 patients treated between 2015 and 2023, all diagnosed by MRI and confirmed by digital subtraction angiography. Endovascular embolization was attempted as the initial treatment modality in all patients using contemporary liquid embolic agents.

Three patients (20%) subsequently required surgical disconnection following unsuccessful or incomplete embolization. Lesions ranged from Th5 to L5, and most patients presented with varying degrees of motor deficits, gait disturbance, paresthesias, or sphincter dysfunction. Neurological improvement occurred in all but one patient, and no treatment-related complications were observed. Prior embolization attempts aided intraoperative localization in surgically treated cases, facilitating precise fistula identification.

These findings demonstrate the feasibility and favorable outcomes of a multidisciplinary, stepwise treatment strategy in this single-center experience. Endovascular embolization served as the initial treatment modality, while surgical disconnection provided an effective complementary option in selected cases where embolization was unsuccessful or incomplete.