Search Results (732)

The tightly controlled and transient acquisition of a motile phenotype by otherwise static epithelial cells (epithelial–mesenchymal transition, EMT) enables the repair of a damaged epithelium. Conversely, a persistent, dysregulated, and exacerbated EMT characterizes epithelial malignancies such as breast carcinoma (BC) and oral squamous cell carcinoma (OSCC), being key for their metastasis and for their escaping anti-tumor immune responses. Herein, we investigated the relationship between EMT signatures and immune cell infiltration across OSCC and metastatic BC with the aim to identify prognostic markers and/or therapeutic targets common to both these malignancies, or unique to OSCC or BC. To this end, we analyzed publicly available transcriptomic datasets to identify coding genes involved in EMT with strong correlation to immune cell signatures. The methodology consisted of data selection, correlation analysis, signature overlap determination, and validation using independent databases. Results indicated that in both OSCC and BC the expression of EMT-related genes is strongly associated with that of immunosuppressive and pro-tumor macrophages. Notably, the FN1 gene coding for the extracellular matrix glycoprotein fibronectin (FN) emerged as the EMT gene common to either tumor types. In confirmation of this, FN protein levels were higher in OSCC and BC tissues than in their normal counterparts. Given FN capability of favoring tumor invasion and metastasis while hindering antitumor immune responses, these data encourage the development of FN antagonists to be used as an adjunct to conventional therapy in the treatment of both OSCC and BC. Full article

Introduction: Massage therapy delivers structured mechanosensory input that can influence brain function, yet the central mechanisms and potential for neuroplastic change have not been synthesized across neuroimaging modalities. This mechanistic review integrates evidence from electroencephalography (EEG), functional MRI (fMRI), and functional near-infrared spectroscopy (fNIRS) to map how massage alters human brain activity acutely and over time and to identify signals of longitudinal adaptation. Materials and Methods: We conducted a scoping, mechanistic review informed by PRISMA/PRISMA-ScR principles. PubMed/MEDLINE, Cochrane Library, Google Scholar, and ResearchGate were queried for English-language human trials (January 1990–July 2025) that (1) delivered a practitioner-applied manual massage (e.g., Swedish, Thai, shiatsu, tuina, reflexology, myofascial techniques) and (2) measured brain activity with EEG, fMRI, or fNIRS pre/post or between groups. Non-manual stimulation, structural-only imaging, protocols, and non-English reports were excluded. Two reviewers independently screened and extracted study, intervention, and neuroimaging details; heterogeneity precluded meta-analysis, so results were narratively synthesized by modality and linked to putative mechanisms and longitudinal effects. Results: Forty-seven studies met the criteria: 30 EEG, 12 fMRI, and 5 fNIRS. Results: Regarding EEG, massage commonly increased alpha across single sessions with reductions in beta/gamma, alongside pressure-dependent autonomic shifts; moderate pressure favored a parasympathetic/relaxation profile. Connectivity effects were state- and modality-specific (e.g., reduced inter-occipital alpha coherence after facial massage, preserved or reorganized coupling with hands-on vs. mechanical delivery). Frontal alpha asymmetry frequently shifted leftward (approach/positive affect). Pain cohorts showed decreased cortical entropy and a shift toward slower rhythms, which tracked analgesia. Somatotopy emerged during unilateral treatments (contralateral central beta suppression). Adjuncts (e.g., binaural beats) enhanced anti-fatigue indices. Longitudinally, repeated programs showed attenuation of acute EEG/cortisol responses yet improvements in stress and performance; in one program, BDNF increased across weeks. In preterm infants, twice-daily massage accelerated EEG maturation (higher alpha/beta, lower delta) in a dose-responsive fashion; the EEG background was more continuous. In fMRI studies, in-scanner touch and reflexology engaged the insula, anterior cingulate, striatum, and periaqueductal gray; somatotopic specificity was observed for mapped foot areas. Resting-state studies in chronic pain reported normalization of regional homogeneity and/or connectivity within default-mode and salience/interoceptive networks after multi-session tuina or osteopathic interventions, paralleling symptom improvement; some task-based effects persisted at delayed follow-up. fNIRS studies generally showed increased prefrontal oxygenation during/after massage; in motor-impaired cohorts, acupressure/massage enhanced lateralized sensorimotor activation, consistent with use-dependent plasticity. Some reports paired hemodynamic changes with oxytocin and autonomic markers. Conclusions: Across modalities, massage reliably modulates central activity acutely and shows convergent signals of neuroplastic adaptation with repeated dosing and in developmental windows. Evidence supports (i) rapid induction of relaxed/analgesic states (alpha increases, network rebalancing) and (ii) longer-horizon changes—network normalization in chronic pain, EEG maturation in preterm infants, and neurotrophic up-shifts—consistent with trait-level recalibration of stress, interoception, and pain circuits. These findings justify integrating massage into rehabilitation, pain management, mental health, and neonatal care and motivate larger, standardized, multimodal longitudinal trials to define dose–response relationships, durability, and mechanistic mediators (e.g., connectivity targets, neuropeptides). Full article

The extracellular matrix (ECM) is a dynamic, tissue-specific network that integrates biochemical and mechanical cues to regulate cell behavior and organ homeostasis. Increasing evidence indicates that dysregulated ECM remodeling is an upstream driver of chronic human diseases rather than a passive consequence of injury. This review summarizes principles of ECM organization, mechanotransduction, and pathological remodeling and highlights translational opportunities for ECM-targeted therapies, biomaterial platforms, and precision diagnostics. We conducted a narrative synthesis of foundational and recent literature covering ECM composition and turnover, stiffness-dependent signaling, and disease-associated remodeling across fibrosis/cardiovascular disease, cancer, and metabolic disorders, together with advances in ECM-based biomaterials, drug delivery, and ECMderived biomarkers and imaging. Across organs, a self-reinforcing cycle of altered matrix composition, excessive crosslinking, and stiffness-dependent mechanotransduction (including integrin–FAK and YAP/TAZ pathways) sustains fibroinflammation, myofibroblast persistence, and progressive tissue dysfunction. In tumors, aligned and crosslinked ECM promotes invasion, immune evasion, and therapy resistance while also shaping perfusion and drug penetration. Translational strategies increasingly focus on modulating ECM synthesis and crosslinking, normalizing rather than ablating matrix architecture, and targeting ECM–cell signaling axes in combination with anti-fibrotic, cytotoxic, or immunotherapeutic regimens. ECM biology provides a unifying framework linking pathogenesis, therapy, and precision diagnostics across chronic diseases. Clinical translation will benefit from standardized quantitative measures of matrix remodeling, mechanism-based biomarkers of ECM turnover, and integrative imaging–omics approaches for patient stratification and treatment monitoring. Full article

Background/Objectives: Cancer persists as a leading concern in the current medical field, and current therapies are limited by toxicity, cost, and resistance. Targeted inhibition of tubulin polymerization is considered as a promising therapeutic strategy for cancer treatment. Methods: Thirty-one new tubulin polymerization inhibitors were designed via molecular hybridization techniques, and BLI technology was employed to quantitatively investigate their interactions with tubulin. Antiproliferative activities against MCF-7, MDA-MB-231, A549, and HeLa cell lines was evaluated using the CCK8 assay. Apoptosis induction and cell cycle arrest were analyzed by flow cytometry. The anti-tumor activity of compound B6 was validated in a mouse melanoma tumor model. Results: Compounds exhibited varying degrees of antiproliferative activity against four tumor cell lines. Among them, compound B6 was the most promising candidate and displayed strong broad-spectrum anticancer activity with an average IC₅₀ value of 2 μM. The mechanism studies revealed that compound B6 inhibited tubulin polymerization in vitro, disrupted cell microtubule networks, and arrested the cell cycle at G2/M phase. Furthermore, B6 displayed significant in vivo antitumor efficacy in a melanoma tumor model with tumor growth inhibition rates of 70.21% (50 mg/kg). Conclusions: This work shows that B6 is a promising lead compound deserving further investigation as a potential anticancer agent. Full article

Background/Objectives: Long COVID (LC) is associated with more than 200 symptoms. This study aimed to evaluate the correlation between symptoms clusters and pharmacological treatment in patients with LC and to explore differences by sex. Methods: We conducted a cross-sectional descriptive study including 304 participants diagnosed with LC according to the World Health Organization criteria. Symptoms during the acute phase, at the time of diagnosis of LC, and those persisting across both phases were collected by anamnesis. Symptoms were grouped into six clusters: systemic, neurocognitive, respiratory/cardiovascular, musculoskeletal, neurological/neuromuscular, and psychological/psychiatric. Drug use was assessed through a questionnaire verified by the medical records, including the consumption of cardiovascular drugs, antidepressants/anxiolytics, and anti-inflammatory/analgesics. Results: Patients reported a mean of 5.23 ± 1.10 symptoms in the acute phase, 4.20 ± 1.70 at LC diagnosis, and 3.83 ± 1.80 persisting across both phases. The most consumed pharmacological group was cardiovascular drugs (43.3%), followed by antidepressants/anxiolytics (34.8%). Psychotropic drugs and anti-inflammatory/analgesic drugs showed a positive association with all symptomatic groups (p < 0.05). Cardiovascular drugs showed a positive association with cardiorespiratory (β = 0.19, p < 0.05), neuromuscular (β = 0.11, p < 0.05), and psychological (β = 0.14, p < 0.05) symptoms. Conclusions: Psychotropic and anti-inflammatory/analgesic drugs were positively associated with all symptom clusters, while cardiovascular drugs were associated only with cardiorespiratory, neuromuscular, and psychological symptoms, highlighting the relevance of better characterization of treatment patterns in this population. Full article

Chronic diabetic wounds are characterized by persistent inflammation, impaired angiogenesis, oxidative stress, and defective tissue remodeling, leading to delayed healing. Cordyceps militaris, a medicinal fungus with known anti-inflammatory and antioxidant properties, has shown therapeutic potential in metabolic disorders; however, its role in diabetic wound repair remains unclear. In this study, we evaluated the wound-healing effects of an aqueous extract of C. militaris using in vitro keratinocyte models and a streptozotocin-induced diabetic mouse model. C. militaris treatment significantly accelerated wound closure, improved epidermal regeneration, and enhanced skin barrier integrity. Mechanistically, C. militaris restored HIF-1α and TGF-β1 expression, promoted cell proliferation and fibroblast activation, and increased the expression of matrix metalloproteinases MMP-1 and MMP-2, indicating enhanced extracellular matrix remodeling. In parallel, excessive inflammatory responses were attenuated, as evidenced by reduced IL-6 and TNF-α levels, along with activation of SIRT1/Nrf2/HO-1 antioxidant signaling pathways. Collectively, these findings demonstrate that C. militaris promotes a balanced wound-healing microenvironment and represents a promising natural therapeutic candidate for the treatment of diabetic wounds. Full article

Mammarenaviruses (MaAv) cause persistent infection in their natural rodent hosts across the world and, via zoonotic events, can cause severe disease in humans. Thus, the MaAv Lassa virus (LASV) in Western Africa and the Junin virus (JUNV) in the Argentinean Pampas cause hemorrhagic fever diseases with significant case fatality rates in their endemic regions. In addition, the globally distributed MaAv lymphocytic choriomeningitis virus (LCMV) is an underrecognized human pathogen of clinical significance capable of causing devastating infections in neonates and immunocompromised individuals. Despite their impact on human health, there are currently no FDA-approved vaccines or specific antiviral treatments for MaAv infections. Existing anti-MaAv therapies are limited to the off-label use of ribavirin, whose efficacy remains controversial; hence, the development of novel therapeutics to combat human pathogenic MaAv is vital. We employed a high-throughput cell-based infection assay to screen the Pandemic Response Box, a collection of 400 diverse compounds with established antimicrobial activity, for MaAv inhibitors. We identified Ro-24-7429, an antagonist of the HIV-1 Tat protein and RUNX family transcription factor 1 inhibitor; WO 2006118607 A2, a dihydroorotate dehydrogenase inhibitor; and verdinexor, a novel selective inhibitor of nuclear export (SINE) targeting the XPO1/CRM1, as potent anti-MaAv compounds. Consistent with their distinct validated targets, verdinexor and WO 2006118607 A2 exhibited very strong synergistic antiviral activity when used in combination therapy. Our findings pave the way for the development of verdinexor as a potent host-directed antiviral against MaAv, which could be integrated into the development of combination therapy with direct- or host-acting antivirals to combat human pathogenic MaAv. Full article

Chronic rhinitis is induced by endotype-diverse inflammatory processes, which complicates effective therapeutic management. According to the current principles of personalized medicine, which also apply to the management of rhinological disorders, the best therapeutic results can be achieved after targeted treatment preceded by analysis of the patient’s endotype. Analysis of immune and cellular mechanisms allows for the use of biological treatment, and its effects provide new information on inflammatory processes in the nasal mucosa. The effects of biological treatment may be particularly interesting in the case of mixed endotypes, which pose a difficult therapeutic challenge. In eosinophilic asthma co-occurring with allergic rhinitis, as well as in eosinophilic asthma associated with non-allergic rhinitis, eosinophils represent a key effector cell population driving the underlying type 2-mediated inflammatory response. The aim of this study is to analyze the efficacy of anti-IL5 or anti-ILR5 therapy in patients with severe eosinophilic asthma and persistent allergic or non-allergic rhinitis. Methods: In this single-center real-life study, the authors analyzed the effects of biological treatment on rhinological symptoms in patients over the age of 18 with severe uncontrolled eosinophilic bronchial asthma with coexisting persistent allergic or non-allergic rhinitis treated with mepolizumab or benralizumab. In all patients, the otolaryngologist performed anterior rhinoscopy. Evaluation of rhinological symptoms and quality of life in patients treated with anti-IL5 or anti-IL5 therapy before and six months after biological treatment was performed using the TNSS and SNOT-22 scales. Results: In total, 67 patients with eosinophilic severe bronchial asthma were included in the study; among them 39 (58.2%) suffered from persistent allergic rhinitis and 28 (41.8%) suffered from chronic non-allergic rhinitis. After six months of treatment, higher absolute differences for SNOT and TNSS were observed in the persistent allergic rhinitis group. Conclusions: Biological treatment with mepolizumab and benralizumab may reduce the severity of rhinological symptoms in both endotypes of inflammation. However, higher therapeutic benefits were observed in patients with co-existing persistent allergic rhinitis. It was demonstrated that, in addition to IgE-mediated responses, the eosinophil represented an important component of the inflammatory reaction in allergic rhinitis. Full article

Sewage sludge is increasingly recognized as a major reservoir for pharmaceuticals and emerging contaminants that are only partially removed by conventional wastewater treatment. This study provides the first comprehensive assessment of these contaminants in biosolids generated from ten major wastewater treatment plants (WWTPs) across Jordan. Different pharmaceuticals were quantified in the sludge samples generated. The results revealed concentrations ranging from 10 to over 2000 µg kg⁻¹, with antibiotics typically showing the highest enrichment (e.g., ciprofloxacin up to 2165 µg kg⁻¹, ofloxacin up to 303 µg kg⁻¹). Anti-inflammatory compounds such as diclofenac reached 196 µg kg⁻¹, while the antimicrobial triclosan exceeded 4700 µg kg⁻¹ in some sludge samples. Carbamazepine, a recalcitrant antiepileptic drug, ranged between 50 and 223 µg kg⁻¹, reflecting both widespread use and strong persistence. Elevated levels of quaternary ammonium compounds (QACs) were also detected. The highest levels were generally associated with large urban WWTPs and plants receiving industrial discharges. Environmental risk assessment (ERA) indicated that the risk for soil biota was acceptable for most cases for low application doses (5–10 t/ha) except for WWTP6-MD, WWTP8-S, and WWTP9-IC, where the risk was non-acceptable. Severe limitations in the risk assessment were noted: reliable toxicity endpoints in terrestrial soil organisms such as microbiota, collembola, and earthworms are few, while deriving endpoints via aquatic available data is not always reliable. Overall, the findings demonstrate that Jordanian sewage sludge contains environmentally relevant levels of pharmaceuticals and QACs and that risk assessment is, therefore, pertinent before any stabilization and realistic land application scenarios are chosen. Full article

Background: Nintedanib and pirfenidone are two anti-fibrotic agents for diseases within the interstitial lung diseases (ILDs) spectrum. Here, we provide a comprehensive analysis regarding treatment persistence and adherence rates for the Greek territory. Methods: This was a retrospective cohort study of patients initiating anti-fibrotic treatment during the period 2019–2023, utilizing data extracted from the National Electronic Prescription Database. Treatment persistence was defined as the duration from the date of the first prescription to the end of follow-up, death, or switching to another agent. Adherence was estimated based on the Medication Possession Ratio (MPR) metric. Results: Overall, 2112 patients were analyzed. The majority were naive, male patients with a diagnosis of idiopathic pulmonary fibrosis (IPF). The overall median treatment persistence was 40.2 months (95% CI: 35.5–44.6). Women and treatment-naive patients demonstrated longer median treatment persistence compared to their counterparts, while older patients demonstrated the lowest median persistence rates. Adherence levels remained high across the follow-up period (90%). Diagnosis of IPF and gastrointestinal comorbidities were associated with a higher risk of discontinuation. Conclusions: We have generated novel data concerning the factors that affect patients’ outcomes under anti-fibrotic therapy. These findings may provide helpful insights for the therapeutic management of ILDs. Full article

Atherosclerosis is a chronic, multifactorial vascular disease and the leading global cause of cardiovascular morbidity. Its development reflects interconnected disturbances in lipid metabolism, endothelial function, inflammation, smooth muscle cell (SMC) phenotypic switching, and extracellular matrix remodeling. Genetic predisposition, including monogenic disorders such as familial hypercholesterolemia and polygenic risk variants, modulates disease susceptibility by altering lipid homeostasis as well as inflammatory and thrombotic pathways. Epigenetic regulators and noncoding RNAs, such as histone modifications, microRNAs, and long noncoding RNAs, further shape gene expression and link environmental cues to vascular pathology. Endothelial injury promotes lipoprotein retention and oxidation, triggering monocyte recruitment and macrophage-driven foam cell formation, cytokine secretion, and necrotic core development. Persistent inflammation, macrophage heterogeneity, and SMC plasticity collectively drive plaque growth and destabilization. Emerging insights into immune cell metabolism, intracellular signaling networks, and novel regulatory RNAs are expanding therapeutic possibilities beyond lipid-lowering. Current and evolving treatments include statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, anti-inflammatory agents targeting interleukin-1 beta (IL-1β) or NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3), and advanced approaches such as gene editing, siRNA, and nanoparticle-based delivery. Integrating multi-omics, biomarker-guided therapy, and precision medicine promises improved risk stratification and next-generation targeted interventions. This review summarizes recent molecular advances and highlights translational opportunities for enhancing atherosclerosis prevention and treatment. Full article

Background/Objectives: The global fight against cancer persists despite advances in prevention and treatment. The current study investigated the phytochemical constituents, antioxidant, anti-inflammatory, and anticancer properties of Eucomis comosa, traditionally used in South Africa to treat elephantiasis and cancer-related conditions. Methods: Phytochemical screening, Fourier transform infrared spectroscopy (FTIR), and liquid chromatography–mass spectrometry (LC-MS) analyses were conducted. Antioxidant activity was measured through DPPH and nitric oxide (NO) radical scavenging assays. The anticancer activity was assessed using the MTT assay. Results: Phytochemical screening confirmed the presence of alkaloids, cardiac glycosides, terpenoids, flavonoids, saponins, and phlobatannins. FTIR analysis of the aqueous extract displayed characteristic peaks at 3278.92 cm⁻¹ for O–H stretch, at 2930.67 cm⁻¹ for C–H stretch, at 1623.97 cm⁻¹ for C=O stretch, 1410.24 cm⁻¹ for C=C stretch and at 931.17 cm⁻¹ for =C–H, while LC-MS identified diverse metabolites, including polyphenols such as flavan-3-ols, flavone glycosides, and chalcones. Among the extracts, methanol showed the strongest DPPH scavenging activity (IC₅₀ = 972.73 µg/mL), followed by ethanol (1296.36 µg/mL). For NO scavenging, methanol again outperformed ethanol, with IC₅₀ values of 1301 µg/mL and 2890 µg/mL, respectively. Cytotoxicity assays demonstrated that the ethanol extract completely inhibited cell growth at concentrations of 100 and 200 µg/mL. Methanol, ethanol, and hexane extracts significantly suppressed cell proliferation in DU-145, PC-3, and SKU-T-1 cancer cell lines at higher concentrations, with IC₅₀ values ranging between 0.2 and 2.5 µg/mL. Conclusions: These findings indicate that the phytochemicals and functional groups present in E. comosa extracts contribute to their dose-dependent antioxidant and anticancer activities, supporting their ethnomedicinal use. Full article

Bioactive natural products (NPs) may play a critical role in cancer progression by targeting nucleic acids and a wide array of proteins, including enzymes. Furthermore, a large number of derivatives (NPDs), including semi-synthetic products and pharmacophores from NPs, have been developed to enhance the solubility and stability of NPs. Acute myeloid leukemia (AML) is a poor-prognosis hematologic malignancy characterized by the clonal accumulation in the blood and bone marrow of myeloid progenitors with high proliferative capacity, survival and propagation abilities. A number of potential pathways and targets have been identified for development in AML, and include, but are not limited to, Fms-like tyrosine kinase 3 (FLT3) and isocitrate dehydrogenases resulting from genetic mutations, BCL2 family members, various signaling kinases and histone deacetylases, as well as tumor-associated antigens (such as CD13, CD33, P-gp). By targeting nucleic acids, FLT3 or CD33, several FDA-approved NPs and NPDs (i.e., cytarabine, anthracyclines, midostaurin, melphalan and calicheamicin linked to anti-CD33) are the major agents of upfront treatment of AML. However, the effective treatment of the disease remains challenging, in part due to the heterogeneity of the disease but also to the involvement of the bone marrow microenvironment and the immune system in favoring leukemic stem cell persistence. This review summarizes the current state of the art, and provides a summary of selected NPs/NPDs which are either entering or have been investigated in preclinical and clinical trials, alone or in combination with current chemotherapy. With multifaceted actions, these biomolecules may target all hallmarks of AML, including multidrug resistance and deregulated metabolism. Full article

Major depressive disorder remains a leading cause of disability worldwide, with conventional antidepressants offering incomplete and often transient relief. Mounting evidence highlights disturbances in tryptophan (Trp) metabolism as a key biological axis linking inflammation, neuroplasticity, and mood regulation. Plant-derived compounds that modulate this pathway, including 5-hydroxytryptophan, isoflavones, berberine, and polyphenols, have emerged as promising candidates for integrative treatment strategies. Yet, despite encouraging preclinical and clinical findings, knowledge gaps persist regarding long-term efficacy, mechanistic specificity, and standardized therapeutic protocols. This narrative review explores how Trp modulators influence central and peripheral mechanisms relevant to depression, from serotonergic synthesis and kynurenine shunting to gut–brain–immune interactions. Evidence from animal models and randomized clinical trials is critically synthesized, with particular attention to outcomes on mood stabilization, anxiety reduction, cognitive function, and sleep regulation. Special emphasis is placed on translational potential, methodological limitations, and the need for harmonized research frameworks. Here we highlight that phytochemical interventions represent a mechanistically informed and biocompatible strategy for advancing depression management. By bridging neurobiology and clinical psychiatry, these insights may pave the way for next-generation therapeutics that integrate dietary, microbiota-targeted, and anti-inflammatory approaches. Broader application of this research could ultimately refine personalized psychiatry, expand therapeutic horizons, and contribute to global mental health resilience. Full article

The HIV-1 envelope glycoprotein gp120 is prominently exposed on the surface of both HIV-1 virions and infected host cells, serving as a key marker of infection. gp120 plays a pivotal role in viral entry by interacting with the primary receptor, CD4, on host cells. Therapeutic strategies targeting the HIV-1 reservoir, such as anti-gp120 antibodies that trigger antibody-dependent cellular cytotoxicity (ADCC) and chimeric antigen receptor T (CAR-T) cells, rely on the presence of gp120 on the surface of infected cells to exert their effects. Consequently, accurate monitoring of gp120 expression on infected cells is essential for evaluating the pharmacological efficacy of these interventions. In this study, a sensitive, specific, and inexpensive enzyme-linked immunosorbent assay (ELISA) for quantifying HIV-1 gp120 glycoprotein was developed using a selected pair of anti-gp120 antibodies. The assay achieved a lower limit of quantitation (LLOQ) of 0.16 pM, demonstrating sensitivity comparable to that of the digital single molecule array (Simoa) platform, which exhibited a LLOQ of 0.23 pM and requires specialized instrumentation. The binding specificity of the antibodies used in the novel assay was confirmed using liquid chromatography–mass spectrometry (LC-MS), and the assay was pharmacologically validated with lysates obtained from 2D10 and MOLT IIIB cell lines. Furthermore, treatment of HIV-infected human primary CD4⁺ T cells with a targeted activator of cell kill (TACK) compound significantly reduced gp120 concentration in CD4⁺ T cell lysate compared to controls. The gp120 marker from infected cell lysates correlated with the number of gp120-positive cells detected by immunocytochemistry, as well as with HIV-1 p24 levels and cell-associated viral RNA measurements. In summary, a novel, simple, and sensitive HIV-1 gp120 ELISA has been developed and validated. This assay holds potential for investigating HIV-1 persistence and evaluating the efficacy of therapeutic agents targeting infected cells. Full article