Search Results (16,142)

Background/Objectives: Retinoblastoma treatment remains limited by therapeutic resistance and toxicity. While melphalan is a key chemotherapeutic agent, its efficacy is constrained by adverse effects. Curcumin has emerged as a potential adjunct owing to its capacity to regulate oxidative stress and oncogenic signaling pathways, including STAT3. This study aimed to assess the synergistic tumor-inhibitory effects of melphalan–curcumin combined treatment and to investigate the roles of ROS, apoptosis, and STAT3-associated signaling, including validation in a three-dimensional (3D) tumor spheroid model. Materials and Methods: Human retinoblastoma (WERI-Rb-1) and normal keratinocyte (HaCaT) cells were exposed to melphalan, curcumin and the combined treatment regimen. Cell viability was analyzed by MTT assay, and drug interactions were analyzed using the Chou–Talalay method. Migration was evaluated by scratch assay. Intracellular ROS levels were quantified using the DCFH-DA assay and confirmed by flow cytometry. Apoptosis was quantified by Annexin V/PI staining, and caspase activity was assessed colorimetrically and by immunocytochemistry. Cytokine levels were determined by ELISA, and gene expression profiling of STAT3 and apoptosis-associated genes were performed using qRT-PCR. Three-dimensional tumor spheroids were established to evaluate treatment responses in a physiologically relevant model. The contribution of ROS was further investigated using N-acetyl-L-cysteine (NAC) pretreatment. Results: The combination of melphalan and curcumin notably reduced WERI-Rb-1 cell viability in a synergistic manner (CI < 1) while exhibiting lower cytotoxicity in HaCaT cells, indicating selective antitumor activity. Co-treatment markedly inhibited cell migration and increased intracellular ROS levels. Cells pretreated with NAC significantly reduced ROS levels accumulation and moderately restored cellular viability, supporting a contributory role of oxidative stress. The combination treatment induced pronounced apoptosis, with increased early and late apoptotic cell populations, enhanced caspase-7 and caspase-9 activity, and elevated caspase-9 protein expression. These effects were associated with upregulation of pro-apoptotic genes (BAX, CASP3, CASP7, CASP9), downregulation of anti-apoptotic genes (BCL2, SURVIVIN), and reduction in STAT3 mRNA expression. In addition, the combination reduced pro-inflammatory cytokine levels. Importantly, these effects were recapitulated in 3D tumor spheroids, where the combination treatment reduced spheroid size and viability and induced structural disruption. NAC-mediated rescue experiments in 3D models further supported the notion that ROS contributes to, but is not solely responsible for, the observed effects. Conclusions: Overall, these results suggest that melphalan and curcumin exert synergistic and selective antitumor effects in retinoblastoma cells, associated with changes consistent with ROS-related effects, mitochondrial apoptotic processes, and STAT3-related transcriptional alterations rather than definitive pathway activation. The validation of these effects in a 3D tumor spheroid model provides additional support for the potential clinical significance of this combined treatment; however, additional protein-level and functional validation is required. Full article

Background/Objectives: Histone deacetylase (HDAC) inhibitors have been shown to prime the response to immunotherapy (IMT) treatment by inducing immune activation and infiltration to target tumor cells. Many studies primarily focus on adaptive immune cells and their expression of pro-inflammatory markers, like somatostatin receptor 2 (SSTR2); however, macrophages are known to help mediate key tumor microenvironment changes. The goal of this study is to evaluate the effects of HDAC inhibitors and IMT on macrophages, their expression of SSTR2, and their impact on the treatment response in triple-negative breast cancer (TNBC). Methods: Cytotoxic effects of HDAC inhibitors on 4T1 mouse mammary carcinoma cells, including suberoylanilide hydroxamic acid (SAHA), were evaluated using flow cytometry. Bone marrow-derived macrophages (BMDMs) were stimulated to M1-like and M2-like phenotypes and treated with SAHA to explore the effects on SSTR2 expression in different macrophage phenotypes. 4T1-tumor-bearing BALB/c mice were used to evaluate the therapy response to four treatments: saline control, SAHA, anti-PD-1 + anti-CTLA-4 checkpoint blockade IMT, or a combination of SAHA + IMT. Additional cohorts of 4T1-tumor-bearing BALB/c mice and NOD SCID mice, which lack adaptive immune cells, were euthanized for early evaluation of tumor-associated macrophage (TAM) populations via flow cytometry and cytokine analysis. One-way independent ANOVAs and log-rank tests were used to compare group differences. Results: SAHA promotes SSTR2 expression on M1-like BMDMs in vitro. SAHA promotes M2-like TAMs in vivo and stimulates pro-inflammatory, anti-tumor cytokine production in combination with IMT. Conclusions: SAHA drives SSTR2 expression and anti-tumor innate immune responses with additive effects in combination with immunotherapy in preclinical TNBC. Full article

Objective: This study aimed to identify clinically modifiable and readily accessible predictors of 30-day mortality in a 10-year candidemia cohort and to assess temporal changes in Candida species distribution. Methods: We retrospectively evaluated 391 hospitalized adults with positive blood cultures for Candida spp. between January 2015 and March 2025. Only the first candidemia episode was included. Demographic characteristics, comorbidities, risk factors, laboratory parameters, antifungal therapy, and outcomes were recorded. Species identification was performed using conventional methods and the VITEK 2 system. Factors associated with 30-day mortality were analyzed using univariate and multivariate logistic regression models. Results: The mean age was 64.5 ± 17.7 years, and 56.3% of patients were male. Most patients (68.8%) were managed in the intensive care unit, and the 30-day mortality rate was 54%. Non-albicans Candida species accounted for 62.7% of isolates, with an increasing trend over time, particularly for Candida glabrata. Fluconazole susceptibility was 79%. In univariate analysis, advanced age, solid tumors, invasive mechanical ventilation, leukocytosis, thrombocytopenia, septic shock, intensive care unit admission, and failure to remove the central venous catheter were associated with mortality. Multivariate analysis identified advanced age, intensive care unit admission, septic shock, failure to remove the central venous catheter, leukocytosis, and thrombocytopenia as independent predictors of 30-day mortality. Conclusions: Candidemia remains a life-threatening infection with high mortality. Central venous catheter management and simple hematological parameters, particularly white blood cell and platelet counts, provide practical tools for early risk stratification. Although the rising prevalence of non-albicans Candida species may require updates in empirical therapy, prompt source control remains essential to improve survival. Full article

Background: Microfibrillar-associated protein 2 (MFAP2) is implicated in various malignancies, yet its specific role and molecular mechanisms in glioblastoma (GBM) progression remain poorly understood. Methods: We analyzed MFAP2 expression in human clinical specimens and murine models. Functional impacts were assessed in U251 cells via gain- and loss-of-function assays. Mechanistic studies explored the interplay between autophagic flux and Wnt/β-catenin signaling. An orthotopic GL261 syngeneic orthotopic model validated these findings in vivo. Results: MFAP2 was significantly overexpressed in GBM, correlating with poor patient prognosis. In vitro, MFAP2 markedly enhanced U251 viability, migration, and invasion while suppressing apoptosis. Mechanistically, MFAP2 triggered autophagic flux, subsequently activating the Wnt/β-catenin cascade and its downstream targets (MMP9, c-Myc, Cyclin D1). Pharmacological inhibition of either autophagy or Wnt signaling effectively abrogated these oncogenic phenotypes. In vivo, MFAP2 knockdown reduced tumor volume by 62.4% and suppressed the autophagy–Wnt axis. Conclusions: MFAP2 is an oncogenic regulator in glioblastoma models that links autophagy activity to Wnt/β-catenin signaling. Our findings support MFAP2 as a candidate prognostic biomarker and a potential therapeutic target; however, additional validation in larger molecularly annotated clinical cohorts and multiple GBM models is warranted. Full article

Background/Objectives: Spontaneous remission (SR) of acute myeloid leukemia (AML) offers unique clinical insights into host anti-tumor immunity. However, the comprehensive clinical landscape and molecular dynamics of blast clearance and subsequent relapse remain unclear. This study aimed to elucidate these dynamics. Methods: We conducted a two-phase observational study: a systematic pooled analysis of 66 adult AML SR cases (1990–2024) to define clinical triggers and outcomes and longitudinal molecular tracking of two institutional cases to map clonal shifts (with immune profiling for Patient 1 and genomic tracking for both). Results: In the pooled analysis, infection was the predominant trigger, accounting for 78.6% (95% CI: 65.6–88.4%) of SR events. The dataset showed male predominance and monocytic leukemia enrichment (57.6% [95% CI: 44.1–70.4%]), suggesting lineage-specific susceptibility. SR duration and relapse risk were independent of the infection trigger, AML subtype, or age. When integrated with these clinical patterns, institutional tracking was consistent with a biphasic evolutionary model: an acute IL-8 surge alongside NKT and CD4+ T cell activation coincided with blast clearance, as observed primarily in Patient 1. Subsequently, the emergence of TP53 or NRAS mutations within persistent DNMT3A-mutated clones during relapse raised the hypothesis that unresolved chronic inflammation could potentially exert selective pressure favoring resistant subclones. Such interpretations remain correlational and require prospective validation. Conclusions: Our findings outline a clinical–evolutionary framework for AML SR. Remission durability likely relies on balancing acute immune activation with underlying clonal stability. These observational insights highlight complex immune-genomic crosstalk, generating hypotheses for future prospective investigations. Full article

Dysregulation of the immune system, gut microbiota alteration, and epithelial dynamics in the colon contribute to the pathogenesis of inflammatory bowel disease (IBD). However, the role of epithelial dynamics, particularly epithelial regeneration, remains incompletely understood. CADM1 encodes an immunoglobulin-superfamily cell adhesion molecule involved in epithelial adhesion, immune cell interactions, and tumor suppression in colon and various cancers. Here, we investigated the role of CADM1 in IBD using a murine model of colitis induced by dextran sulfate sodium in both wild-type and conventional Cadm1-deficient (Cadm1^−/−) mice. Cadm1^−/− mice exhibited more severe colitis than wild-type mice with increased mortality (64% vs. 10%) and delayed recovery. Cadm1^−/− mice showed reduced numbers of Ki-67-positive cells in colonic crypts and delayed epithelial regeneration, whereas no significant differences were observed in epithelial apoptosis, intestinal permeability, or immune responses. Immunohistochemistry revealed that CADM1 expression was restricted to regenerative crypt cells in wild-type mice with nuclear accumulation of β-catenin and phospho-Akt. Furthermore, CADM1 overexpression in colon epithelial cells enhanced Tcf-transcriptional activity in a β-catenin-dependent manner. Immunohistochemistry of human IBD materials revealed that CADM1 expression also correlated with nuclear β-catenin accumulation in crypt epithelial cells. Collectively, CADM1 appears to promote colonic epithelial regeneration through the PI3K/Akt/β-catenin axis to protect against severe epithelial injury in IBD. Full article

Pharmacokinetic modeling in Positron Emission Tomography (PET) imaging has become a cornerstone in cancer research, offering insights into tumor development and progression. These models facilitate the quantification of radiotracer distribution and metabolism, enabling precise measurement of physiological parameters essential for cancer diagnosis, staging, and treatment monitoring. However, accurate pharmacokinetic modeling depends on reliable input function acquisition and partial volume correction techniques to minimize biases in quantitative PET metrics. This review provides a comprehensive overview of current methodologies and advancements in pharmacokinetic modeling for PET oncology imaging. We discuss techniques for acquiring input functions, including arterial, venous, and image-derived input functions (IDIFs), along with population-based input functions (PBIFs). Their strengths, limitations, and clinical applications are critically evaluated. Additionally, we examine quantitative methods such as partial volume correction (PVC) that mitigate the spatial resolution limitations of PET, improving radiotracer quantification in small or heterogeneous tumors. Furthermore, we explore advanced kinetic modeling techniques, including compartmental models, graphical approaches, and data-driven methods, highlighting recent innovations such as machine learning and Bayesian modeling. Key areas for future research in PET pharmacokinetic modeling include integrating hybrid imaging modalities, developing robust patient-specific input functions, and leveraging machine learning to streamline modeling processes. These advancements aim to enhance the precision and clinical utility of PET imaging in oncology, leading to more personalized cancer treatment strategies. Full article

Background: Reliable biomarkers that capture tumor–host interactions and predict treatment resistance in extensive-stage small cell lung cancer (SCLC) remain limited. We evaluated the prognostic and predictive value of the pretreatment lactate dehydrogenase-to-albumin ratio (LAR), an integrative biomarker reflecting metabolic activity, systemic inflammation, and host nutritional status. Methods: This multicenter, retrospective cohort study included patients with extensive-stage SCLC treated at five tertiary centers between 2016 and 2024. Pretreatment LAR was calculated using baseline serum lactate dehydrogenase and albumin levels and dichotomized using a Youden index-derived cut-off at the 12-month overall survival (OS) horizon. Time-dependent receiver operating characteristic (ROC) analyses using inverse probability weighting were performed to assess discriminative performance. Survival outcomes were evaluated using Kaplan–Meier estimates and Cox proportional hazards models. Associations with platinum resistance and lack of objective treatment benefit (defined as progressive disease as best response) were examined using logistic regression models. Results: A total of 223 patients were included. Elevated LAR was associated with inferior OS (median, 15.8 vs. 25.2 months; log-rank p < 0.001) and progression-free survival (7.9 vs. 11.5 months; p < 0.001). In multivariable analysis, LAR remained independently associated with OS (HR, 1.43; 95% CI, 1.04–1.95; p = 0.028). LAR demonstrated modest but consistently superior discriminative performance compared with other inflammatory indices for both 12-month OS (area under the curve [AUC], 0.692) and 6-month progression-free survival (PFS) (AUC, 0.646), with statistically significant differences in DeLong comparisons. Higher LAR was independently associated with increased odds of platinum resistance (adjusted odds ratio [aOR], 2.31; 95% CI, 1.41–3.81; p = 0.001) and lack of objective treatment benefit (adjusted OR, 2.04; 95% CI, 1.33–3.14; p = 0.001). Conclusions: Pretreatment LAR is a clinically accessible and biologically integrative biomarker associated with survival and treatment resistance in extensive-stage SCLC. By capturing tumor–host interactions, LAR may support risk stratification and identify patients at increased risk of early treatment failure. Prospective validation is warranted to define its role in biomarker-driven clinical decision-making. Full article

Background/Objectives: Prostate cancer (PCa) is the second most commonly diagnosed cancer in men globally. Radiation oncologists often find PCa tumor characterization and outcome prediction challenging. Therefore, the potential for artificial intelligence (AI) implementation in radiation oncology has increased in recent years. This systematic review aims to evaluate the efficacy of AI algorithms in characterizing PCa tumors and predicting post-therapy outcomes. Methods: A total of 2055 studies were identified through a comprehensive search across PubMed and Scopus, then exported to Covidence. Inclusion criteria focused on prospective and retrospective cohort studies as well as randomized clinical trials (RCTs) published between 2015 and 2024 that explored the implementation of AI in tumor characterization and outcome prediction of PCa. Two independent reviewers evaluated each paper, and evaluation metrics such as specificity, sensitivity, accuracy, and area under the curve (AUC) were analyzed. The Risk of Bias in Non-randomized Studies of Interventions, Version 2 (ROBINS-I V2) tool was used to assess the risk of bias (ROB). Results: Across the 19 studies analyzed, there was no significant difference in model performance between machine learning (ML) and deep learning (DL) models. AI models using multi-input strategies (e.g., radiomics with clinical markers) generally performed better than single-input models. Of the imaging modalities used for radiomic feature extraction, multiparametric MRI (mpMRI)-trained AI models consistently achieved the highest performance. Conclusions: AI displays considerable potential for integration into clinical workflows for PCa management. However, further studies utilizing larger datasets and external cohorts independent of the sample population are needed to validate clinical utility and improve model transparency for reliable implementation. Full article

Objectives: This study aimed to investigate the biological role and molecular mechanism of the RNA m⁵C methyltransferase NSUN4 in cervical cancer progression, with a focus on its involvement in ferroptosis regulation. Methods: Differential expression and survival analyses were performed using TCGA and GEPIA datasets. Functional enrichment and GSEA identified pathways associated with NSUN4 dysregulation. NSUN4 expression was validated in clinical tissues by qRT-PCR, Western blot, and immunohistochemistry. Gain- and loss-of-function assays, including CCK-8, colony formation, and Transwell assays, were conducted to assess cell proliferation and invasion. Furthermore, a nude mouse subcutaneous xenograft model was established to validate the oncogenic role of NSUN4 in vivo. Ferroptosis was evaluated using specific inhibitors and measurement of GSH and ferroptosis-related proteins. RIP, m⁵C-RIP, RNA stability, and dual-luciferase assays were performed to explore the underlying mechanism. Results: NSUN4 was markedly upregulated in cervical cancer tissues and correlated with poor prognosis. Functionally, NSUN4 enhanced tumor cell growth, migration, and invasion while inhibiting ferroptosis. Mechanistically, NSUN4 bound to and stabilized C-MYC mRNA via m⁵C methylation, activating the PI3K/Akt signaling pathway and promoting ferroptosis resistance. Conclusions: NSUN4 promotes cervical cancer progression by stabilizing C-MYC mRNA through m⁵C modification, leading to PI3K/Akt activation and suppression of ferroptosis. These findings identify NSUN4 as a novel oncogenic regulator and potential therapeutic target in cervical cancer. Full article

Background: Cytokine-like receptor family 1 (CRLF1) has been implicated in tumor progression, yet its prognostic function and mechanistic actions in prostate cancer (PCa) remain elusive. Objective: This investigation sought to clarify the functional role, molecular mechanisms, and clinical relevance of CRLF1 in the progression of PCa. Methods: We conducted extensive bioinformatics analyses utilizing the protein interaction networks and the TCGA-PRAD dataset. CRLF1 and cartilage oligomeric matrix protein (COMP) expression were validated in clinical samples by qRT-PCR and Western blot (WB). Functional assessments, including Transwell invasion, flow cytometry, CCK-8, and wound healing, were conducted in vitro. An in vivo xenograft tumor model was used for further validation. Mechanistic investigations involved genetic perturbation (overexpression and inhibition) of CRLF1 and COMP. Results: Compared to benign tissues, the levels of CRLF1 and COMP were markedly elevated in PCa tissues. Bioinformatics assessments illustrated a robust positive relationship between CRLF1 and COMP, suggesting COMP may function as a downstream mediator. In vitro and in vivo investigations illustrated that silencing CRLF1 significantly suppressed PCa cell growth, invasion, and tumor progression, while enhancing apoptosis. Importantly, suppressing COMP counteracted the cancer-promoting effects triggered by CRLF1 overexpression. At the mechanistic level, CRLF1 facilitates tumor progression by modulating COMP to activate the FAK/PI3K/AKT signaling cascade. Conclusions: Our outcomes demonstrate that CRLF1 promotes PCa progression by targeting COMP to stimulate the FAK/PI3K/AKT signaling axis. This newly identified CRLF1/COMP/FAK/PI3K/AKT pathway underscores CRLF1 as a potential biomarker and therapeutic target for PCa. Full article

Cancer threatens the health and lives of people around the world and causes a heavy economic burden on families and society. Dysbiosis of the gut microbiota has been observed in cancer patients and is an important factor in cancer progression. Quercetin, a widely distributed dietary flavonol, exhibits pleiotropic anti-cancer activities in preclinical models. Importantly, recent studies reveal a bidirectional crosstalk between quercetin and the gut microbiota that may critically shape its biological effects. Specifically, gut microbiota enzymes mediate quercetin biotransformation and produce tumor-suppressive quercetin metabolites. On the other hand, quercetin remodels specific gut microbial species and their metabolites to promote anti-tumor activity. This review provides a timely and systematic synthesis of the latest findings regarding quercetin, gut microbiota, and cancer. Furthermore, we discuss strategies to enhance this interaction for improved cancer therapy. By highlighting the pivotal role of the gut microbiota, this review offers novel insights and a refined theoretical framework to guide future research and potential clinical translation of quercetin in cancer prevention and treatment. Full article

Cutaneous T-cell lymphoma (CTCL), primarily mycosis fungoides (MF) and Sézary syndrome (SS), has long been characterized as a neoplasm of mature memory T cells, based on monoclonal T-cell receptor (TCR) rearrangements and tissue-resident memory (TRM)/central memory (TCM) T-cell phenotypes. This review synthesizes converging population-genetic, multi-omic, and single-cell evidence to argue that this characterization is incomplete and that a progenitor-based model better accounts for the full spectrum of disease biology. We present evidence that initiating mutations arise in hematopoietic stem or early lymphoid progenitor survive thymic selection, and diversify after TCR assembly, resulting in branched evolution across both blood and skin. In SS, paired analyses reveal > 200 shared variants between CD34⁺ progenitors and Sézary cells, as well as signal-joint T-cell receptor excision circle (sjTREC) positivity, providing direct progenitor-level evidence. In MF, convergent signals, multiple malignant clonotypes per lesion, greater blood–skin than skin–skin clonotype overlap, and compartment-specific CNV subclones, implicate hematogenous seeding and reseeding. Population-scale lymphoid clonal hematopoiesis and lymphoid-pattern mosaic chromosomal alterations define a compatible antecedent state. Spatial single-cell atlases and trajectory analyses map site-conditioned programs in skin, including Th2-skewed cytokines, microbial responses, and UV signatures, that select and expand subclones and explain inter- and intra-patient heterogeneity. This framework reconciles mature immunophenotypes with upstream initiation and clarifies why compartment-focused therapies often reshape rather than eradicate disease. It yields testable predictions and actionable implications: trials should pair multicompartment cytoreduction with strategies that attenuate progenitor-derived reservoirs, restore immune balance, and repair skin barrier dysfunction. A progenitor-initiated, niche-adapted model provides a coherent scaffold for more durable control in CTCL. Full article

Background: High-grade serous ovarian carcinoma (HG-SOC) remains the most lethal gynecological malignancy, largely due to intrinsic or acquired resistance to platinum-based chemotherapy. Although large-scale sequencing studies have delineated the genomic landscape of HG-SOC, clinically actionable biomarkers predictive of platinum response and outcome are still lacking. This study aimed to identify genomic alterations associated with platinum sensitivity, resistance, or refractoriness, and to assess their prognostic relevance. Methods: Tumor DNA from 24 HG-SOC patients with optimal cytoreductive resection, classified as platinum-sensitive (n = 9), platinum-resistant (n = 8), or platinum-refractory (n = 7) underwent targeted next-generation sequencing of 409 cancer-associated genes. Somatic variants were filtered and classified for oncogenicity using established criteria incorporating predicted functional impact, REVEL scores, and population allele frequencies. Associations between mutational profiles, platinum response, and overall survival (OS) were evaluated using Kaplan–Meier and Cox regression analyses. Key findings were validated in the TCGA ovarian serous carcinoma (TCGA-OV) dataset using survival analyses. Results: A total of 1367 protein-altering somatic variants across 301 genes were identified. While TP53 mutations were ubiquitous, platinum-resistant and platinum-refractory tumors showed enrichment of pathogenic alterations affecting DNA repair, transcriptional regulation, epigenetic modification, and oncogenic signaling, including FANCA, ATF1, MAF, NCOA2, PIK3CA, and TET1. Mutations in these genes were associated with reduced overall survival in exploratory analyses (median 2.5–9 months vs. 27.5–45 months). Multivariate analysis identified FANCA and ATF1 as potential independent predictors in exploratory modeling. In the TCGA-OV cohort, patients harboring pathogenic variants in a multi-gene panel derived from this study (excluding BRCA1/2) exhibited significantly worse survival compared with both BRCA1/2-mutated cases and the overall cohort. Conclusions: This exploratory study identifies a set of genomic alterations converging on transcriptional and epigenetic regulation, DNA repair, and oncogenic signaling that are associated with platinum resistance and adverse prognosis in HG-SOC. Independent validation in TCGA supports the potential clinical relevance of this mutational signature. These findings warrant further validation in larger prospective cohorts and functional studies to clarify their role as biomarkers of aggressive disease and therapeutic vulnerability. Full article

Dehydrothyrsiferol (DT), a brominated oxasqualenoid from the red alga Laurencia viridis, represents a compelling example of this framework. This review establishes DT as a model Smart Secondary Metabolite based on the convergence of a unique molecular architecture of rigid stereogroups connected by flexible bonds; a high metabolic yield (0.42% w/w of crude extract); potent selective bioactivity against kinetoplastids and drug-resistant tumors; multi-target modulation of protein phosphatase 2A (PP2A) and cell-surface integrins; and distinctive chemotaxonomic relevance within Macaronesian communities. Its biosynthesis proceeds through stereocontrolled epoxide-opening cascades, generating an evolutionarily refined scaffold. Ecologically, DT operates as a multifunctional shield, providing antifouling protection and deterring herbivory. Pharmacologically, it acts as a selective signaling modulator, triggering integrin-mediated cell death (IMD) in resistant cancer cells and inducing mitochondrial collapse in protozoa. In vivo studies in murine models of cutaneous leishmaniasis have demonstrated an 87% reduction in lesion size, reinforcing its promise as a lead structure. Full article