Search Results (50)

Direct chemical reprogramming provides a potentially scalable approach for generating retinal lineage-associated cells without genetic manipulation. In this study, human Tenon’s capsule fibroblasts were converted into retinal progenitor-like cells using a defined small-molecule cocktail. Retinal lineage-associated features were evaluated by immunofluorescence staining, quantitative reverse-transcription PCR, Western blot analysis, and bulk RNA sequencing, showing upregulation of neural and retinal markers, including VSX2, and transcriptomic remodeling consistent with transcriptional features associated with neuronal differentiation programs. Functional responsiveness was assessed by glutamate-evoked intracellular calcium imaging, revealing glutamate-responsive intracellular calcium dynamics in induced cells but not in parental fibroblasts. For in vivo assessment, induced cells were delivered via intravitreal transplantation in Wistar rats and subretinal transplantation in Long–Evans rats. One month after transplantation, structural and functional evaluations using optical coherence tomography, electroretinography, and histological analyses showed localized alterations in retinal structure at the subretinal injection site, while no significant differences were observed in scotopic ERG responses under the present experimental conditions. In contrast, fibroblast transplantation showed more prominent structural alterations under similar conditions. Human nuclei-positive signals were detectable in a subset of eyes, exhibiting focal and heterogeneous distribution within retinal regions at the one-month endpoint. Collectively, these suggest the induction of retinal lineage-associated molecular and functional features, with short-term functional tolerability observed in vivo under the present experimental conditions. Full article

Patients with heavily calcified coronary arteries represent a challenge in percutaneous coronary intervention (PCI), as severe calcification impairs device delivery and limits optimal stent expansion, leading to higher risks of stent thrombosis, restenosis, and adverse clinical outcomes. Approximately 20% of patients undergoing PCI exhibit severe coronary calcification, which independently predicts incomplete revascularization, increased mortality, and higher rates of major adverse cardiovascular events over mid-term follow-up. Recent advances have focused on improving the assessment and management of calcified lesions. Intracoronary imaging modalities, including intravascular ultrasound and optical coherence tomography, allow precise detection and characterization of calcium burden, overcoming the limitations of angiography. These tools play a pivotal role in guiding procedural strategy, enabling tailored selection of calcium-modifying techniques based on lesion morphology, and optimizing stent deployment. Technological innovations have significantly expanded therapeutic options. While non-compliant balloon angioplasty alone is often insufficient, adjunctive devices such as cutting and scoring balloons improve plaque modification in focal disease. Atherectomy techniques, including rotational and orbital systems, are effective for more complex lesions but require technical expertise and carry procedural risks. Intravascular lithotripsy has emerged as a promising, less aggressive modality capable of fracturing deep calcium, while excimer laser atherectomy offers an alternative for resistant lesions. Despite these advances, current evidence supporting calcium-modifying strategies is largely based on procedural outcomes rather than definitive improvements in long-term clinical endpoints. Meta-analyses and randomized trials have not demonstrated clear superiority of any single technique, and most studies remain underpowered. Intriguingly, recent data suggest that outcomes in treated calcified lesions may approximate those of non-calcified disease, raising the hypothesis that these technologies could mitigate the adverse impact of calcification. However, this remains unproven, highlighting the urgent need for adequately powered randomized trials to determine their true clinical benefit. Full article

Background/Objectives: Secondary hyperparathyroidism (SHPT) is a common and clinically significant complication of advanced chronic kidney disease and may require surgical intervention when medical therapy fails. This study aimed to evaluate the association between parathyroid gland burden, defined by gland number and size parameters, and biochemical disease severity in patients undergoing parathyroidectomy for SHPT, and to assess the concordance between preoperative imaging findings and intraoperative observations. Although parathyroid gland enlargement is a hallmark of SHPT, the clinical relevance of parathyroid gland number and overall gland burden in relation to biochemical disease severity and the accuracy of preoperative imaging remains incompletely defined. Methods: This single-center, retrospective observational study included adult patients who underwent parathyroidectomy for secondary hyperparathyroidism between January 2015 and December 2020. Demographic, clinical, laboratory, imaging, intraoperative, and histopathological data were analyzed. Parathyroid gland burden was assessed based on gland number, largest gland diameter, and total gland burden. Associations between gland morphology and biochemical parameters were evaluated using correlation analyses and multivariable logistic regression. Agreement between preoperative imaging and intraoperative findings was assessed using diagnostic performance metrics, contingency analysis, and the weighted kappa coefficient. Results: A total of 101 patients were included. Patients with three or more enlarged parathyroid glands had significantly higher preoperative parathyroid hormone and alkaline phosphatase levels, higher serum phosphorus levels, and lower calcium and vitamin D levels (all p < 0.05). Total gland burden and largest gland diameter were positively correlated with parathyroid hormone and alkaline phosphatase levels. In multivariable analysis, higher parathyroid hormone levels, longer dialysis duration, and vitamin D deficiency were independently associated with high gland burden. Preoperative imaging demonstrated moderate agreement with intraoperative findings (weighted kappa = 0.46; 95% CI, 0.29–0.63). Separate evaluation of imaging modalities showed that both ultrasonography and scintigraphy had relatively high sensitivity but limited specificity for detecting extensive gland involvement. Conclusions: In patients undergoing parathyroidectomy for secondary hyperparathyroidism, increased parathyroid gland burden is associated with greater biochemical disease severity. Preoperative imaging shows limited concordance with intraoperative findings and should be interpreted cautiously, particularly in the presence of multiglandular disease. These findings support the integration of morphological parameters into comprehensive preoperative assessment while highlighting the need for larger prospective, multicenter studies with standardized imaging protocols and long-term follow-up. Full article

Primary hyperparathyroidism (PHPT) in the pediatric population is a rare but clinically important endocrine disorder that poses significant diagnostic and therapeutic challenges. In contrast to adult PHPT, which is often detected incidentally, pediatric patients are frequently symptomatic at diagnosis, with manifestations reflecting prolonged exposure to hypercalcemia and elevated parathyroid hormone levels. Neonatal forms, particularly neonatal severe hyperparathyroidism, represent life-threatening conditions requiring prompt biochemical recognition and urgent intervention. The heterogeneity of clinical presentation and the rarity of the disease contribute to delayed diagnosis and increased risk of end-organ complications. Although hereditary syndromes are proportionally more frequent in children than in adults, sporadic PHPT remains the most common etiology in pediatric patients and is typically caused by a single parathyroid adenoma. Genetically determined forms, including multiple endocrine neoplasia syndromes, hyperparathyroidism–jaw tumor syndrome, and calcium-sensing receptor-related disorders, are often associated with multiglandular disease, earlier onset, and a higher risk of persistence or recurrence. Biochemical confirmation remains the cornerstone of PHPT diagnosis, while diagnostic imaging plays an important role in preoperative localization and surgical planning. High-resolution cervical ultrasound is the preferred first-line imaging modality in pediatric patients due to its excellent diagnostic performance and absence of ionizing radiation. Functional and advanced cross-sectional imaging techniques should be applied in a stepwise manner in selected cases with inconclusive first-line imaging or suspected ectopic disease, balancing diagnostic yield against radiation exposure. Surgical management remains the definitive treatment for pediatric PHPT. The extent of surgery is determined by disease etiology, localization findings, and intraoperative assessment, with focused parathyroidectomy favored in sporadic single-gland disease and more extensive approaches required in genetically determined forms. This review highlights a structured diagnostic and therapeutic pathway for pediatric PHPT, emphasizing the integration of biochemical testing, imaging strategies, genetic evaluation, and individualized surgical management to optimize outcomes and reduce long-term morbidity. Full article

Primary hyperoxalurias (PHs) are rare autosomal recessive disorders characterized by overproduction of oxalate, a metabolic end product that readily forms calcium oxalate crystals. Excess hepatic oxalate leads to recurrent kidney stones, nephrocalcinosis, and progressive renal injury, often culminating in end-stage kidney disease (ESKD). Once renal clearance declines, systemic oxalate accumulation can cause multisystem deposition. PH encompasses three types—PH1, PH2, and PH3—caused by deficiencies in the hepatic enzymes AGT, GRHPR, and HOGA1, respectively, resulting in accumulation of glyoxylate and subsequent oxalate overproduction. Clinical presentation varies from infantile oxalosis to adult-onset recurrent nephrolithiasis, with PH1 generally being the most severe. Diagnosis relies on urinary oxalate measurements, plasma oxalate in advanced chronic kidney disease, urinary metabolite profiling, imaging, and genetic testing. Management includes hyperhydration, citrate supplementation, pyridoxine for responsive PH1 patients, dialysis and transplantation when required, while RNA interference therapies targeting glycolate oxidase or LDHA have demonstrated substantial biochemical efficacy in PH1 and represent promising emerging therapeutic options, although long-term clinical outcome data remain limited and broader applicability to other PH types is still under investigation. Future strategies focus on modulating intestinal oxalate absorption, gut microbiome therapies, oxalate-degrading enzymes, and novel gene-editing approaches. Early diagnosis and individualized management are critical to prevent kidney injury and systemic oxalosis. In this review, we summarize the genetic, biochemical, and clinical features of PH and discuss current and emerging therapeutic strategies. Full article

Background/Objectives: Pediatric osteoporosis is a multifactorial condition characterized by impaired bone mineralization and increased fracture risk, particularly vertebral compression fractures. This study aims to evaluate the diverse etiology, diagnostic challenges, and treatment options for pediatric osteoporosis in a cohort of affected children. Methods: We reviewed eleven pediatric patients (aged 5–16 years) diagnosed with vertebral fractures and osteoporosis, who were hospitalized between 2020 and 2024 at the Department of Endocrinology and Metabolic Diseases at PMMH-RI in Lodz. Clinical evaluation included medical history, physical examination, biochemical markers of bone metabolism, and imaging techniques such as dual-energy X-ray absorptiometry (DXA) to determine underlying causes of bone fragility. Results: The cohort presented a broad etiological spectrum, including seven patients with genetic disorders (e.g., mutations in COL1A1, LRP5, SGMS2, and ALPL genes) and secondary osteoporosis due to chronic diseases requiring prolonged glucocorticoid therapy (two patients with Duchenne muscular dystrophy (DMD), one patient with Crohn’s disease) or endocrinological disorders (one patient with Cushing disease). Vertebral fractures were confirmed in all patients, with back pain as the predominant symptom. Low bone mass (BMD Z-score < −2.0) was observed in eight individuals; in others, clinical signs of skeletal fragility were present despite Z-scores above this threshold. Mild biochemical abnormalities included hypercalciuria (3/11 cases) and vitamin D deficiency (6/11 cases). Height adjustment improved BMD interpretation in short-stature patients. Most children received bisphosphonate therapy, supplemented with calcium and vitamin D. In two patients, bisphosphonates were not used due to lack of parental consent or underlying conditions in which such treatment is not recommended. Conclusions: Pediatric osteoporosis requires a multidisciplinary diagnostic and therapeutic approach, integrating clinical, biochemical, and genetic factors. It is a heterogeneous and often underrecognized condition, with vertebral fractures frequently serving as its earliest sign—even in the absence of overt symptoms or low bone mass. This underscores the need for clinical vigilance, as significant skeletal fragility may occur despite normal BMD values. Importantly, pediatric osteoporosis may also impact the attainment of peak bone mass and ultimately affect final adult height. Early diagnosis through thorough assessment, including height-adjusted DXA, and a multidisciplinary approach are essential to ensure timely management and prevent long-term complications. Full article

Background/Objectives: Cardiotoxicity remains a leading cause of drug withdrawal. Conventional preclinical models, such as two-dimensional (2D) cell cultures and animal studies, often fail to accurately predict human cardiac responses. While 2D cultures lack the complex architecture and dynamic functionality of native myocardium, interspecies differences limit the translational relevance of animal models. The objective of this study was to develop a human-relevant, in vitro platform that enables predictive and functional assessment of drug-induced cardiotoxicity. Methods: Here, we present a high-throughput in vitro platform for cardiotoxicity screening using three-dimensional (3D) cardiac tissues derived from human induced pluripotent stem cells (hiPSCs) within a thermoresponsive extracellular matrix-derived hydrogel. The hydrogel enables homogeneous encapsulation, differentiation in 3D, and long-term assembly into a functional cardiac tissue. Maturation was validated by immunostaining for cardiac-specific markers, and calcium imaging was employed to monitor electrical signal propagation. Contractile performance, defined by beat rate and contraction amplitude, was quantified using video-based motion analysis. The platform was applied to evaluate the dose-dependent effects of various cardioactive compounds, including β-adrenergic agonists ((-) epinephrine and dopamine), a cardiotoxic chemotherapeutic (doxorubicin), a sinus node inhibitor (ivabradine), a calcium channel blocker (verapamil), and a β-adrenergic antagonist (metoprolol). Results: The engineered cardiac tissues exhibited functional maturation and stable contractile behavior. Drug testing demonstrated compound-specific, dose-dependent functional responses. For each compound, the system faithfully reproduced the expected physiological responses. Conclusions: This human-relevant, scalable platform enables sensitive, multiparametric functional assessment of cardiac tissues, offering a cost-effective and predictive tool for preclinical drug safety testing. By bridging the gap between in vitro assays and human physiology, it holds promise to enhance translational accuracy while reducing reliance on animal models. Full article

Background and Clinical Significance: Tyrosine kinase inhibitors (TKIs) have transformed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) into a largely manageable chronic disease. However, off-target toxicities are increasingly recognized; rarer complications such as bone marrow edema (BME) remain underreported. BME is a radiological syndrome characterized by excess intramedullary fluid on fat-suppressed T2/STIR magnetic resonance imaging sequences and may progress to irreversible osteochondral damage if unrecognized. We report a case series of TKI-associated BME and propose a practical diagnostic-therapeutic framework. Case Presentation: We describe three patients with Ph+ CML who developed acute, MRI-confirmed BME of the lower limb during TKI therapy. Case 1 developed unilateral then bilateral knee BME, temporally associated first with dasatinib and subsequently with imatinib; symptoms improved after TKI interruption, bisphosphonate therapy, and supportive measures, and did not recur after switching to bosutinib. Case 2 presented with proximal femoral BME during long-term imatinib; imatinib was stopped, intravenous neridronate administered, and bosutinib initiated with clinical recovery and later near-complete radiological resolution. Case 3 experienced multifocal foot and ankle BME during imatinib; symptoms resolved after drug discontinuation and bisphosphonate therapy, and disease control was re-established with bosutinib without recurrence of BME. All patients underwent molecular monitoring and mutational analysis to guide safe therapeutic switching. Discussion: Temporal association across cases and the differential kinase profiles of implicated drugs suggest PDGFR (and to a lesser extent, c-KIT) inhibition as a plausible mechanistic driver of TKI-associated BME. PDGFR-β blockade may impair pericyte-mediated microvascular integrity, increase interstitial fluid extravasation, and alter osteoblast/osteoclast coupling, promoting intramedullary edema. Management combining MRI confirmation, temporary TKI suspension, bone-directed therapy (bisphosphonates, vitamin D/calcium), symptomatic care, and, when required, therapeutic switching to a PDGFR-sparing agent (bosutinib) led to clinical recovery and preservation of leukemia control in our series. Conclusions: BME is an underrecognized, potentially disabling, TKI-related adverse event in CML. Prompt recognition with targeted MRI and a multidisciplinary, stepwise approach that includes temporary TKI adjustment, bone-directed therapy, and consideration of PDGFR-sparing alternatives can mitigate morbidity while maintaining disease control. Prospective studies are needed to define incidence, risk factors, optimal prevention, and management strategies. Full article

Neuregulins (NRGs) are ligands of tyrosine kinase receptors from the ErbB family and play multiple developmental roles. NRG1–ErbB signaling regulates myelination and has been associated with amyotrophic lateral sclerosis (ALS) pathology. Given the potential therapeutic relevance of this pathway for motor neuron (MN) diseases, we employed a transgenic (TG) mouse with persistent neuronal overexpression of neuregulin type III (NRG1-III) to investigate its impact on the neuromuscular system. We performed an analysis of phenotypic changes in this TG model, including motor behavior, neuropathological evaluation by immunocytochemistry and ultrastructural examination of the spinal cord, peripheral nerves, and neuromuscular junctions (NMJs). Calcium dynamics in cultured MNs were also examined. We found that cholinergic C-boutons on TG MNs, where NRG1-III typically accumulates, exhibited upregulation of C-bouton-associated proteins and expansion of the subsynaptic cistern (SSC)-associated endoplasmic reticulum. Calcium imaging revealed altered homeostasis in TG MNs, accompanied by the upregulation of molecules linked to axonal plasticity. At NMJs, regressive changes involving autophagic dysregulation were observed. These alterations were accompanied by increased motor activity in behavioral tests. Overall, our findings indicate that persistently elevated NRG1-III signaling compromises MN connectivity and long-term health, a factor to consider when developing therapeutic strategies for neurodegenerative diseases such as ALS. Full article

Introduction: Direct pulp capping (DPC) aims to preserve the vitality of the dental pulp by placing a protective biocompatible material over the exposed pulp tissue to facilitate healing. There are several calcium-silicate materials that have been designed to promote mineralization and the regulation of inflammation. These have strong potential for the repair and regeneration of dental pulp. Among them, Biodentine (BD) and EndoSequence RRM Putty (ES) have been found to promote in vitro and in vivo mineralization while minimizing some of the limitations of the first-generation calcium-silicate-based materials. Theracal-LC (TLC), a light-cured, resin-modified calcium-silicate material, is a newer product with potential to improve the clinical outcomes of DPC, but existing studies have reported conflicting findings regarding its biocompatibility and ability to support pulpal healing in direct contact with the pulp. A comprehensive assessment of the biocompatibility and pulpal protection provided by these three capping materials has not yet been performed. Aim: We aimed to quantify the inflammatory response, dentin bridge formation, and material adaptation following DPC using three calcium-silicate materials: ES, BD, and TLC. Materials and Methods: DPC was performed on the maxillary first molar of C57BL/6 female mice. Maxilla were collected and processed at 1 and 21 days post-DPC. The early inflammatory response was measured 24 h post-procedure using confocal imaging of anti-Lys6G6C, which indicates the extent of neutrophil and monocyte infiltration. Reparative mineralized bridge formation was assessed at 21 days post-procedure using high-resolution micro-computed tomography (micro-CT) and histology. Lastly, the homogeneity of the capping materials was evaluated by quantifying voids in calcium-silicate restorations using micro-CT. Results: DPC using TLC induced less infiltration of Lys6G6C⁺ cells at 24 h than BD or ES. BD promoted higher volumes of tertiary dentin than TLC, but TLC and ES showed no significant differences in volume. No differences were observed in material adaptation and void spaces among the three capping materials. Conclusions: All three materials under investigation supported pulp healing and maintained marginal integrity. However, TLC induced a lower inflammatory response on day 1 and induced similar levels of tertiary dentin to ES. These observations challenge the common perception that resin-based capping materials are not suitable for direct pulp capping. Our findings underscore the need to balance biological responses with physical properties when selecting pulp capping materials to improve long-term clinical success. Full article

Mild traumatic brain injury (mTBI) remains a clinical challenge, particularly in cases with normal computed tomography (CT) findings but persistent or evolving symptoms. Conventional diagnostic approaches relying solely on clinical criteria and neuroimaging often lack adequate sensitivity and may lead to unnecessary radiation exposure. Recent advances in biomarker research have identified several blood-based proteins such as glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), S100 calcium-binding protein B (S100B), Tau protein, neuron-specific enolase (NSE), and neurofilament light chain (NFL) as potential tools for improving diagnostic precision and guiding clinical decisions. In this study, we synthesize current evidence evaluating the diagnostic and prognostic utility of these biomarkers using sensitivity, specificity, negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). GFAP and UCH-L1 have shown high sensitivity in detecting intracranial lesions and are now FDA-cleared for emergency department triage within 12 h of injury. While S100B remains widely investigated, its low specificity limits its application beyond select clinical scenarios (i.e., in patients without polytrauma). Additionally, Tau, NSE, and NFL are emerging as prognostic markers, with studies suggesting associations with persistent symptoms and long-term neurocognitive outcomes. Overall, the integration of biomarker-based data into clinical workflows may enhance early mTBI diagnosis, reduce reliance on imaging, and enable individualized follow-up and prognostic stratification. Future research should refine optimal sampling windows and explore multimarker panels to maximize diagnostic and prognostic performance. Full article

Background: Transcatheter aortic valve implantation (TAVI) has revolutionized the treatment of severe aortic valve stenosis (AS). Balloon post-dilatation (PD) remains an important procedural step to optimize valve function by resolving incomplete valve expansion, which may lead to paravalvular regurgitation and other potentially adverse effects. There are only limited data on the predictors, incidence, and clinical impact of PD during TAVI. Methods: This retrospective, single-center study analyzed 585 patients who underwent TAVI (2016–2022). Pre-procedural evaluations included transthoracic echocardiography and CT angiography to assess key parameters, including the aortic valve calcium score (AVCS); aortic valve calcium density (AVCd); aortic valve maximal systolic transvalvular flow velocity (AV Vmax); and aortic valve mean systolic pressure gradient (AV MPG). We identified imaging predictors of PD and evaluated associated clinical outcomes by analyzing procedural endpoints (according to VARC-3 criteria) and long-term survival. Results: PD was performed on 67 out of 585 patients, with elevated AV Vmax (OR: 1.424, 95% CI: 1.039–1.950; p = 0.028) and AVCd (OR: 1.618, 95% CI: 1.227–2.132; p = 0.001) emerging as a significant independent predictor for PD in TAVI. Kaplan–Meier survival analysis revealed no significant differences in short- and mid-term survival between patients who underwent PD and those who did not. Interestingly, patients requiring PD exhibited a lower incidence of adverse events regarding major vascular complications, permanent pacemaker implantations and stroke. Conclusions: The study highlights AV Vmax and AVCd as key predictors of PD. Importantly, PD was not associated with increased procedural adverse events and did not predict adverse events in this contemporary cohort. Full article

Perioperative and long-term postoperative major adverse cardiovascular events (MACE) are a leading cause of morbidity and mortality in patients undergoing noncardiac surgery. In selected high-risk patients, when information about cardiovascular status may influence surgical decisions, preoperative risk stratification is reasonable, with stress imaging being the preferred method. Coronary computed angiography (CCTA) and coronary artery calcium score (CACS) offer direct anatomical assessment of atherosclerotic coronary arteries and help gauge the extent and severity of coronary artery disease. Strong evidence supports that CCTA and CACS, either alone or in combination, are reliable methods for assessing the risk of both perioperative and long-term postoperative MACE, often demonstrating equal or superior prognostic performance compared to traditional imaging tools. Moreover, integrating CCTA or CACS into standard preoperative imaging protocols further enhances perioperative risk prediction and improves the ability to accurately stratify patients. Future research is needed to better define the role of CCTA and CACS in preoperative cardiovascular risk evaluation of patients undergoing noncardiac surgery. Full article

Background: Terahertz (THz) waves, lying between millimeter waves and infrared light, may interact with biomolecules due to their unique energy characteristics. However, whether THz waves are neurally regulated remains controversial, and the underlying mechanism is elusive. Methods: Mouse brain slices were exposed to 1.94 THz waves for 1 h. Synaptic plasticity was evaluated via transmission electron microscopy (TEM), long-term potentiation (LTP), and neuronal class III β-tubulin (Tuj1) and synaptophysin (SYN) expression. Immunofluorescence (IF) and electrophysiology were used to identify neurons sensitive to THz waves. The calcium activity of excitatory neurons, glutamate receptor currents, and glutamate neuron marker expression was also assessed using calcium imaging, a patch clamp, and Western blotting (WB). Optogenetics and chemogenetics were used to determine the role of excitatory neurons in synaptic plasticity impairment after THz wave exposure. NMDA receptor 2B (GluN2B) was overexpressed in the ventral hippocampal CA1 (vCA1) by a lentivirus to clarify the role of GluN2B in THz wave-induced synaptic plasticity impairment. Results: Exposure to 1.94 THz waves increased postsynaptic density (PSD) thickness and reduced the field excitatory postsynaptic potential (fEPSP) slope and Tuj1 and SYN expression. THz waves diminished vCA1 glutamatergic neuron activity and excitability, neural electrical activity, and glutamate transporter function. THz waves reduced N-methyl-D-aspartate receptor (NMDAR) current amplitudes and NMDAR subunit expression. Activating vCA1 glutamatergic neurons through optogenetics and chemogenetics mitigated THz wave-induced synaptic plasticity impairment. GluN2B subunit overexpression improved synaptic plasticity marker expression, synaptic ultrastructure, and the fEPSP slope. Conclusions: Exposure to 1.94 THz waves decreased synaptic plasticity, glutamatergic neuron excitability, and glutamatergic synaptic transmission in the vCA1. Glutamatergic neuron activation and GluN2B overexpression alleviated THz wave-induced synaptic plasticity impairment; thus, neuromodulation could be a promising therapeutic strategy to mitigate the adverse effects of THz radiation. Full article

Heart failure with reduced ejection fraction due to ischemic cardiomyopathy remains a significant clinical challenge. Electrical conduction delays exacerbate symptoms by causing uncoordinated contractions, reducing pumping efficiency, and increasing mortality. Right ventricular pacing further worsens dyssynchrony, while resynchronization therapy improves outcomes but has a high non-responder rate. Given these limitations, bundle branch pacing engages the heart’s conduction system, restoring synchronized contraction and enhancing cardiac function. This review examines the impact of left-bundle-branch-block-induced dyssynchrony, the role of advanced imaging in assessing ventricular function, and the clinical outcomes of bundle branch pacing in heart failure patients. Specifically, we explore the mechanical and hemodynamic effects of left bundle branch block, imaging techniques for dyssynchrony evaluation, and the comparative benefits of bundle branch pacing versus resynchronization therapy. Conduction delays impair function, increase myocardial stress, and worsen clinical outcomes. Advanced imaging plays a critical role in patient selection, identifying those most likely to benefit from conduction system pacing. By restoring electrical coordination, bundle branch pacing enhances ventricular function, reduces hospitalizations, and promotes reverse remodeling. It offers similar or superior benefits to conventional resynchronization therapy, regulates stress hormones, reduces oxidative damage, and improves calcium handling. Bundle branch pacing represents a significant advancement in heart failure management, but careful patient selection remains crucial. Future research should focus on optimizing implantation techniques and validating long-term benefits through large-scale clinical trials. Full article