Search Results (295)

Remote photoplethysmography (rPPG) extracts physiological signals from facial videos by analyzing subtle skin color variations caused by blood flow. While this technology enables contactless health monitoring, it also raises privacy concerns because facial videos reveal both identity and sensitive biometric information. Existing privacy-preserving techniques, such as blurring or pixelation, degrade visual quality and are unsuitable for practical rPPG applications. This paper presents rePPG, a framework that inserts a desired rPPG signal into facial videos while preserving the original facial appearance. The proposed method disentangles facial appearance and physiological features, enabling replacement of the physiological signal without altering facial identity or visual quality. Skin segmentation restricts modifications to skin regions, and a cycle-consistency mechanism ensures that the injected rPPG signal can be reliably recovered from the generated video. Importantly, the extracted rPPG signals are evaluated against the injected target physiological signals rather than the subject’s original physiological state, ensuring that the evaluation measures signal rewriting accuracy. Experiments on the PURE and UBFC datasets show that rePPG successfully embeds target PPG signals, achieving 1.10 BPM MAE and 95.00% PTE6 on PURE while preserving visual quality (PSNR 24.61 dB, SSIM 0.638). Heart rate metrics are computed using a 5-second temporal window to ensure a consistent evaluation protocol. Full article

Protein-losing enteropathy (PLE) is an uncommon and often underrecognized manifestation of lymphoproliferative disorders and may be difficult to diagnose when conventional gastrointestinal investigations are unrevealing. We present an 82-year-old woman with recurrent hospital admissions initially spanning six months for diarrhea, weight loss, peripheral edema, and persistent hypoalbuminemia. Initial upper gastrointestinal endoscopy was normal, and colonoscopy was deferred due to intercurrent infection. Despite extensive laboratory and radiologic evaluation, including routine biochemical testing and imaging, the etiology of PLE remained unclear. Peripheral blood flow cytometry subsequently identified a small kappa-restricted monoclonal B-cell population compatible with marginal zone lymphoma, later confirmed on bone marrow biopsy, raising suspicion for gastrointestinal involvement. Video capsule enteroscopy demonstrated diffuse erosive and ulcerative disease throughout the small intestine, providing an anatomical explanation for the patient’s protein loss. Following lymphoma-directed therapy, repeat capsule enteroscopy showed complete normalization of the small bowel mucosa. This case highlights the diagnostic value of combining peripheral blood flow cytometry and capsule endoscopy in unexplained protein-losing enteropathy, a rare and diagnostically challenging presentation of indolent lymphoma, and illustrates the role of capsule imaging in both disease localization and treatment monitoring. As a single-case report, these findings are not generalizable, and further studies are required to evaluate the broader applicability of this diagnostic approach. Full article

Background/Objectives: Glioblastoma multiforme (GBM) is the most infiltrative, treatment-resistant, and deadly brain tumor in adults. Given the extremely malignant phenotype of the GBM cells, the high intratumoral heterogeneity, and the limited efficacy of the vast majority of chemotherapeutics due to the restrictive nature of the blood–brain barrier, GBM remains largely incurable. Methods: Utilizing the U87, U251, and T98G GBM cell lines, diverse in vitro approaches (Western blotting, quantitative real-time PCR, flow cytometry, immunofluorescence, Luc-reporter analysis, microscopic examination, and scanning electron microscopy), and pharmacological inhibition, we investigated for the first time the cell death decisions in the GBM cells in response to the LCS1269 treatment. Results: We showed that LCS1269 collapsed the mitochondrial potential and triggered both intrinsic and extrinsic apoptosis. Importantly, our findings demonstrated that LCS1269-mediated apoptosis was paralleled by an induction of both MLKL-dependent necroptosis and caspase-3/GSDME-dependent pyroptosis. Using a combination of specific inhibitors, we further demonstrated that apoptosis, necroptosis, and pyroptosis provoked by LCS1269 occur simultaneously and orchestrate a peculiar form of programmed cell death, which is known as PANoptosis. We subsequently found that LCS1269-induced PANoptosis may be initiated either through the RIPK1-PANoptosome alone or through the integrated ZBP1-, AIM2-, and RIPK1-PANoptosomes. Additionally, we revealed that LCS1269-mediated PANoptosis may be closely related to micronuclei formation. Conclusions: Taken together, our results confirm that LCS1269 is a promising anti-glioblastoma agent that is capable of effectively promoting GBM cell death via PANoptosis. Full article

Articular cartilage, a highly specialised and avascular tissue, exhibits limited regenerative potential following trauma or degenerative conditions such as osteoarthritis (OA). Conventional surgical interventions, including microfracture and autologous chondrocyte implantation (ACI), have shown limited long-term efficacy due to donor site morbidity and restricted cell proliferation. In this context, mesenchymal stromal cells (MSCs) have emerged as a promising alternative owing to their multipotency, self-renewal capacity, and low immunogenicity. While bone marrow (BM) remains the traditional source of MSCs, recent studies have reported that peripheral blood-derived mesenchymal stromal cells (PB-MSCs) may possess chondrogenic, osteogenic, and adipogenic potential comparable to that of BM-derived MSCs. PB-MSCs can be harvested through minimally invasive methods, thereby avoiding the complications associated with BM aspiration. Experimental evidence indicates that PB-MSCs exhibit strong cell viability, proliferative potential, and the ability to synthesise cartilage-specific extracellular matrix proteins, such as type II collagen and sulphated glycosaminoglycans, within three-dimensional scaffolds. Immunophenotypically, PB-MSCs express mesenchymal markers including CD29, CD44, CD90, and CD105 while lacking hematopoietic markers CD34 and CD45. Flow cytometry analyses reveal that CD105⁺ populations increase following cryopreservation, highlighting their clinical utility. In contrast to these experimentally defined PB-MSCs, the term peripheral blood stem cells (PBSCs) is used in clinical studies to describe heterogeneous, non-cultured peripheral blood-derived cell preparations, typically enriched in hematopoietic stem and progenitor cells following granulocyte colony-stimulating factor (G-CSF) mobilisation, without full mesenchymal characterisation. In vitro studies confirm successful tri-lineage differentiation, whereas in vivo investigations have demonstrated effective cartilage regeneration using PB-based clinical approaches, including postoperative intra-articular administration of hyaluronic acid (HA) combined with PBSCs, as well as implantation of PBSCs covered with a collagen membrane. Furthermore, advancements in biomaterial engineering, such as poly(ethylene glycol)–cysteine–arginine–glycine–aspartic acid (PEG-CRGD) hydrogels, have enhanced PB-MSC adhesion, proliferation, and chondrogenic differentiation while promoting immunomodulation through M2 macrophage polarisation. Despite these promising outcomes, the available evidence remains limited and heterogeneous, with substantial variability in cell definitions, experimental models, and clinical study designs, which currently constrains definitive conclusions regarding clinical efficacy. Future research should focus on optimising isolation protocols, understanding molecular pathways governing PB-MSC chondrogenesis, and standardising clinical applications. Overall, PB-MSCs represent a viable, less invasive, and translationally relevant cell source for cartilage regeneration and regenerative orthopaedic therapies Full article

Normal pregnancy is associated with uterine and vascular remodeling by matrix metalloproteinases (MMPs) to facilitate placental blood flow and uterine expansion for the growing fetus. Increases in MMP-2 and MMP-9 in response to estrogen and progesterone promote placentation, uteroplacental vascularization and fetal growth during healthy pregnancy, but are altered in preeclampsia (PE). PE is characterized by hypertension in pregnancy (HTN-Preg) and fetal growth restriction (FGR). Predisposing genetic, demographic and environmental factors alter uteroplacental MMPs, immune response and integrins leading to apoptosis of invasive trophoblasts, inadequate spiral arteries remodeling, and reduced uteroplacental perfusion pressure (RUPP). Ensuing placental ischemia causes imbalance between anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) and pro-angiogenic placental growth factor (PlGF) and promotes the release of tumor necrosis factor-α (TNF-α), hypoxia-inducible factor, reactive oxygen species, and angiotensin AT₁ receptor agonistic autoantibodies. Systemically, these bioactive factors target vascular endothelial cells, smooth muscle cells, and extracellular matrix, causing endothelial dysfunction, vasoconstriction, inadequate vascular remodeling, and HTN-Preg, while locally they diminish uteroplacental remodeling and cause FGR. In support, animal models of HTN-Preg induced by RUPP or infusion of sFlt-1 or TNF-α show decreases in vascular MMP-2, MMP-9 and vasodilation, increases in MMP-1, MMP-7 and vasoconstriction, collagen accumulation, and arterial stiffness. Also, decreases in uterine MMP-2 and MMP-9 could impede uterine expansion and lead to preterm birth. Conversely, PlGF and TNF-α antagonist reversed MMPs imbalance and collagen accumulation, and improved vascular function, blood pressure, and pup weight in HTN-Preg models. Persistent postpartum changes in MMPs could affect maternal hemorrhage, future pregnancies, and HTN, and cause fetal programming of cardiovascular and metabolic diseases. Understanding the aberrant uteroplacental and vascular signaling and remodeling by MMPs could help design new biomarkers and remedies for PE. Targeting bioactive factors and rectifying MMP imbalance could improve vascular and uteroplacental remodeling, and manage HTN-Preg, FGR and PE. Full article

Background: Meniscal injuries are common athletic injuries, and isolated meniscal repair is a critical procedure for restoring knee function. However, rehabilitation protocols after meniscal repair remain controversial. This systematic review aimed to evaluate rehabilitation protocols to determine the best strategies for enhancing recovery following isolated meniscal repair. Objectives: Analyze current rehabilitation protocols following isolated meniscal repair, focusing on the efficacy of approaches in improving functional outcomes and reducing recovery time. This study also aims to identify gaps in the existing literature and provide recommendations for future studies. Data sources: Search was conducted using PubMed, Scopus, and Web of Science databases, covering studies published between May 2015 and May 2024. Inclusion criteria: Studies reporting on isolated meniscal repair with defined postoperative rehabilitation protocols and quantifiable outcome measures. Data extraction: Focused on patient demographics, meniscal tear types, repair techniques, and rehabilitation outcomes. The methodological quality of the included studies was assessed, and narrative synthesis was conducted. Results: The review included 13 studies with significant variability in rehabilitation protocols and outcomes. Early weight-bearing and range of motion exercises have been associated with improved recovery in some studies for stable meniscal tears. However, conservative approaches have better outcomes in patients with complex tears. The use of adjunctive therapies such as blood flow restriction training has demonstrated potential in enhancing muscle preservation and overall recovery. Conclusions: Rehabilitation protocols after meniscal repair surgery should be individualized. Although innovative protocols show promise, further research is needed to standardize rehabilitation approaches and optimize long-term outcomes. Full article

Background: Adipose tissue is a crucial endocrine organ, and obesity, due to its associated chronic inflammation and oxidative stress, disrupts adipokine secretion. These adipokines can be detected not only in blood but also in saliva. Dietary changes are a crucial part of managing obesity, encompassing a balanced diet, increased physical activity, and lifestyle modifications. Moreover, adding functional foods like amaranth and canola oils, recognized for their health benefits, may further improve metabolic and inflammatory health. These products have anti-inflammatory effects and may help reduce the pro-inflammatory activity of adipose tissue, thereby improving systemic and oral health. The study aimed to assess the impact of a 3-week calorie-restricted diet, supplemented with canola or amaranth oil on salivary adipokines, i.e., serpin A12, plasminogen activator inhibitor-1 (PAI-1), and tumor necrosis factor receptor-1 (TNF-R1), pH, and salivary flow in obese patients. Methods: A total of 115 adults with obesity (BMI > 30 kg/m²) were enrolled and placed on a 3-week calorie-restricted diet. The study group (n = 44) received additional supplementation: 21 participants received 20 mL of canola oil daily, and 23 received 20 mL of amaranth oil. The control group (n = 71) followed the same calorie-restricted diet without oil supplementation. Non-stimulated saliva was collected twice, for 20 min each time, before and after the intervention, to evaluate flow rate, pH, and concentrations of serpin A12, PAI-1, and TNF-R1. Concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Results: An increase in saliva flow rate was observed in patients supplemented with amaranth oil (p = 0.0367). Both the amaranth oil and canola oil groups showed a significant rise in salivary pH (p = 0.0425). Across all participants, the 3-week calorie-restricted diet resulted in a reduction in salivary PAI-1 (p = 0.0339), serpin A12 (p = 0.0001), and TNF-R1 (p = 0.0058). Conclusions: The 3-week calorie-restricted diet contributed to a decrease in the concentration of adipokines in saliva. The low-calorie diet, combined with supplementation of amaranth and canola oils, increased salivary flow and resulted in higher pH values, indicating greater alkalinity. Full article

Fluorescence emission-guided blood flow and lymph node location detection are important observation methods in cancer removal surgery, where near-infrared LED illumination is used to induce fluorescence emission. However, conventional LED light sources have narrow beam widths, resulting in a limited excitation area and a restricted field of view (FOV). In this study, we propose a balanced optical illumination module that combines a beam-focusing condenser lens and a beam-diffusing lens to expand the beam width while efficiently redistributing optical energy. When only the LED was used, the beam diameter and central irradiance were 4.0 cm and 1.43 mW/cm², respectively. With the condenser lens, the beam diameter remained nearly unchanged (3.98 cm), while the central irradiance decreased to 0.91 mW/cm². When the condenser was combined with the proposed diffuser structure, the beam diameter increased to 14.1 cm, corresponding to an approximately 3.5-fold expansion, while the central irradiance was measured at 0.72 mW/cm², reflecting the redistribution of optical energy from an initially Gaussian-like irradiance distribution into a wider and more uniform illumination area. This irradiance level exceeds the minimum threshold of 0.6 mW/cm² required to induce fluorescence emission, as defined for the experimental working distance of 30 cm and LED power of 200 mW. By integrating the irradiance distributions of both the bare LED and the proposed structure over their respective illuminated surfaces, the measured total power is physically consistent with energy conservation, showing an expected transmission loss of 18.8% due to optical absorption and scattering. These results demonstrate that the proposed beam diffusion-concentration approach provides an effective and practical solution for wide-field fluorescence-guided lesion observation during cancer removal surgery. Full article

Trypanosomiasis, caused by flagellated protozoa of the genus Trypanosoma, has recently emerged as a major threat to aquaculture in China, particularly in farmed large yellow croaker (Larimichthys crocea). Outbreaks lead to high mortality rates and severe economic losses. Conventional diagnostic tools, such as blood-smear microscopy and molecular assays including polymerase chain reaction or quantitative polymerase chain reaction (qPCR), are often limited by low sensitivity during early infection or by their dependence on sophisticated instruments and trained personnel, restricting their utility in field conditions. To address these challenges, a multienzyme isothermal rapid amplification (MIRA) assay coupled with a lateral-flow dipstick (LFD) was developed for the rapid detection of trypanosoma strains circulating in L. crocea targeting the 18S ribosomal ribonucleic acid gene. After optimizing primer-probe sets, the assay performance was evaluated using plasmid standards and a panel of common aquaculture pathogens. The MRA-LFD assay consistently detected plasmid DNA at concentrations as low as 0.01 fg/µL (≈2.1 copies/µL) and demonstrated no cross-reactivity with other pathogens. Using clinical DNA samples positive for Trypanosoma, the detection limit was 100 fg µL⁻¹. Validation with 150 tissue samples from fish with and without clinical symptoms demonstrated high diagnostic consistency (94%) with qPCR results, confirming the reliability of the assay. This MIRA-LFD platform provides a sensitive, specific and portable diagnostic tool for early detection of Trypanosoma infections in large yellow croaker, offering valuable support for surveillance and disease management in aquaculture. Full article

Background/Objectives: Cognitive impairment and sleep disturbances are highly prevalent in individuals with multiple sclerosis (MS), particularly during middle age, and negatively affect functional independence and quality of life. Although physical exercise has demonstrated cognitive and sleep-related benefits in MS, tolerance to high-intensity training is often limited. Blood flow restriction (BFR) training, which combines low-load resistance exercise with partial vascular occlusion, has emerged as a feasible alternative. This study aimed to evaluate the effects of a 12-week BFR training program on performance in specific cognitive domains and sleep quality in middle-aged adults with MS. Methods: A randomized controlled trial was conducted in 65 adults with relapsing–remitting multiple sclerosis (RRMS) aged 40–65 years and an Expanded Disability Status Scale score below 7. Participants were randomly assigned to a BFR training group or a usual-care control group. The intervention consisted of supervised low-load resistance training with BFR performed twice weekly for 12 weeks. Outcomes assessed before and after the intervention included processing speed (Symbol Digit Modalities Test), executive function (Trail Making Test A and B), verbal fluency (Isaacs Set Test), and self-reported sleep quality (Pittsburgh Sleep Quality Index). Results: Compared with controls, participants in the BFR group showed significant improvements in specific cognitive domains, including processing speed, executive function, and verbal fluency. Significant reductions were also observed in self-reported global sleep disturbance and daytime dysfunction. No adverse events were reported. Conclusions: A 12-week BFR training program improved performance in key cognitive domains and self-reported sleep quality in middle-aged adults with MS, supporting its feasibility and potential clinical relevance as an exercise-based intervention. Full article

Background: Pulmonary atresia (PA) with ventricular septal defect (VSD) and major aortopulmonary collateral arteries (MAPCAs), a life-threatening congenital heart defect (CHD), is frequently associated with abnormal pulmonary blood flow and vascular remodeling, causing hypoxia and heart failure. Segmental pulmonary hypertension (PH), a distinct PH type, may exist in some patients. Pulmonary vasodilators have been considered for treatment; however, evidence of their efficacy and safety remains lacking. Methods: A systematic review was conducted using PubMed, MEDLINE, The Cochrane Library, and Ichushi Web, encompassing studies from inception to May 2023. Inclusion criteria focused on patients with PA/VSD/MAPCAs treated with PH medications. Results: Of 86 studies screened, 6 met the inclusion criteria, including 1 cohort study and 5 case reports, comprising 22 patients. The most frequently administered medications were sildenafil (14 cases) and bosentan (12 cases), with 16 patients receiving monotherapy. Clinical improvements were observed in pulmonary vascular resistance (8/8 patients), oxygen saturation (8/19 patients), and symptoms (19/21 patients). Adverse effects were noted in five patients, including treatment discontinuation in two. Conclusions: PH medications may benefit some patients with PA/VSD/MAPCAs; however, the extremely limited sample size (n = 22) and substantial heterogeneity in anatomy, age, surgical status, and treatment regimens severely limit interpretability and clinical applicability. Considering the potential benefits and risks associated with these medications, their use should be considered cautiously and restricted to specialized centers with expertise in CHD and PH management. Full article

Background/Objectives: Blood Flow Restriction training has been suggested as a method to enhance strength and neuromuscular adaptations at low exercise intensities. Early reports indicate potential effects on pain perception, myofascial stiffness, and flexibility; however, the evidence remains inconsistent. Method: Twenty-two healthy adults participated in a randomized, within-participant, contralateral-controlled design, performing 5 min of treadmill walking (4–5 km/h) with and without blood flow restriction at 70% arterial occlusion pressure. Pressure pain threshold, hip range of motion, and hamstring stiffness were measured before and after the intervention. Adverse effects were recorded. Results: Changes in pain threshold, range of motion, and myofascial stiffness were similar between conditions. The pressure pain threshold decreased slightly in both conditions, regardless of BFR, while range of motion and stiffness remained unchanged. Mild, short-lasting sensations (cuff pressure, erythema, tingling) were reported, with no adverse events. Conclusions: A single short session of low-intensity BFR walking did not change pain sensitivity, flexibility, or myofascial stiffness in healthy adults. The protocol was well tolerated. Repeated or longer interventions may be needed to see measurable effects. Full article

This study aimed to investigate the efficacy of a 12-week blood flow restriction (BFR) resistance training (BFRRT) program in enhancing anaerobic power. Changes in anaerobic power were compared following 12 weeks of resistance training using three approaches: low-load resistance training with BFRRT at 30% of one-repetition maximum (1RM), traditional high-load resistance training (HRT) at 80% of 1RM, and traditional low-load resistance training (LRT) at 30% of 1RM. Twenty-one male college students were randomly assigned to the BFRRT (n = 7), HRT (n = 7), or LRT (n = 7) groups. The BFR for BFRRT was applied to the proximal femur at 100–130 mmHg. Each group exercised three times per week for 12 weeks. Anaerobic power and metabolic fatigue levels were evaluated using the Wingate Anaerobic Test (WAnT) every 3 weeks, with blood lactate concentrations measured before and after each session. Outcomes included peak power, mean power, fatigue rate, and time to peak power, analyzed via two-way mixed-model analysis of variance. The results revealed a significant group × time interaction for anaerobic peak power, with the blood flow restriction training group demonstrating earlier improvements compared with traditional high-load resistance training, while no significant between-group differences were observed for mean power. Post hoc analysis revealed that BFRRT improved peak power by Week 6, HRT by Week 9, and LRT showed no improvements. BFRRT significantly enhanced anaerobic power in a shorter duration compared with HRT, despite utilizing lower loads and normal-speed exercises. These findings suggest that BFRRT is an effective method for improving anaerobic power while utilizing lower external loads than HRT. Full article

Glioblastoma (GBM) remains one of the most treatment-resistant human malignancies, largely due to the interplay between disrupted fluid dynamics, immune evasion, and the structural complexity of the tumor microenvironment; in addition to these, treatment resistance is also driven by intratumoral heterogeneity, glioma stem cell persistence, hypoxia-induced metabolic and epigenetic plasticity, adaptive oncogenic signaling, and profound immunosuppression within the tumor microenvironment. Emerging evidence shows that dysfunction of the glymphatic system, mislocalization of aquaporin-4, and increased intracranial pressure compromise cerebrospinal fluid–interstitial fluid exchange and impair antigen drainage to meningeal lymphatics, thereby weakening immunosurveillance. GBM simultaneously remodels the blood–brain barrier into a heterogeneous and permeable blood–tumor barrier that restricts uniform drug penetration yet enables tumor progression. These alterations intersect with profound immunosuppression mediated by pericytes, tumor-associated macrophages, and hypoxic niches. Advances in imaging, including DCE-MRI, DTI-ALPS, CSF-tracing PET, and elastography, now allow in vivo characterization of glymphatic function and interstitial flow. Therapeutic strategies targeting the fluid-immune interface are rapidly expanding, including convection-enhanced delivery, intrathecal and intranasal approaches, focused ultrasound, nanoparticle systems, and lymphatic-modulating immunotherapies such as VEGF-C and STING agonists. Integrating barrier modulation with immunotherapy and nanomedicine holds promise for overcoming treatment resistance. Our review synthesizes the mechanistic, microenvironmental, and translational advances that position the glymphatic–immune axis as a new frontier in glioblastoma research. Full article

Background/Objectives: Chagas disease, caused by Trypanosoma cruzi, remains a major neglected tropical disease with limited therapeutic options restricted to benznidazole and nifurtimox, both associated with significant toxicity and reduced efficacy during chronic infection. Seeking novel, safe, and sustainable chemotherapeutic candidates, two new saturated cardanol-derived phospholipid analogs—LDT10 and LDT119—were rationally designed based on the molecular scaffold of miltefosine and biosourced from cashew nut shell liquid (CNSL). This study aimed to evaluate the pharmacokinetic properties of these compounds in silico and assess their antiparasitic activity, cytotoxicity, and morphological and ultrastructural effects on all developmental forms of T. cruzi in vitro. Materials and Methods: In silico ADMET predictions (SwissADME, pkCSM) were performed to determine bioavailability, pharmacokinetic behavior, CYP inhibition, mutagenicity, and hepatotoxicity. Antiproliferative activity was evaluated in epimastigotes, trypomastigotes, and intracellular amastigotes using dose–response assays and flow cytometry. Cytotoxicity was assessed in HEPG2 and HFF-1 cells using resazurin-based viability assays. Morphological and ultrastructural alterations were investigated through scanning (SEM) and transmission (TEM) electron microscopy. Reactive oxygen species (ROS) generation was quantified with H₂DCFDA after 4 h and 24 h of exposure. Results: In silico analyses indicated favorable drug-like profiles, high intestinal absorption (>89%), absence of mutagenicity or hepatotoxicity, and non-penetration of the blood–brain barrier. LDT10 was not a P-gp substrate, and LDT119 acted as a P-gp inhibitor, suggesting reduced efflux and higher intracellular retention. Both compounds inhibited epimastigote proliferation with low IC₅₀ values (LDT10: 0.81 µM; LDT119: 1.2 µM at 48 h) and reduced trypomastigote viability (LD₅₀ LDT10: 2.1 ± 2 µM; LDT119: 1.8 ± 0.8 µM). Intracellular amastigotes were highly susceptible (IC₅₀ LDT10: 0.48 µM; LDT119: 0.3 µM at 72 h), with >90% inhibition at higher concentrations. No cytotoxicity was observed in mammalian cells up to 20 µM. SEM revealed membrane wrinkling, pore-like depressions, rounded cell bodies, and multiple flagella, indicating cell division defects. TEM showed Golgi disorganization, autophagic vacuoles, mitochondrial vesiculation, and abnormal kinetoplast replication, while host cells remained structurally preserved. Both compounds induced significant ROS production in trypomastigotes after 24 h in a dose-dependent manner. Conclusions: LDT10 and LDT119 exhibited potent and selective in vitro activity against all developmental stages of T. cruzi, with low micromolar to submicromolar IC₅₀/LD₅₀ values, minimal mammalian cytotoxicity, and extensive morphological and ultrastructural damage consistent with disruption of phospholipid biosynthesis pathways. Combined with favorable in silico pharmacokinetic predictions, these CNSL-derived phospholipid analogs represent promising candidates for future Chagas disease chemotherapy and warrant further in vivo evaluation. Full article