Acute myeloid leukemia (AML) shows substantial biological and clinical heterogeneity that extends beyond leukemia-intrinsic genetic alterations. MRC1, which encodes the myeloid receptor CD206, has been linked to monocytic differentiation and immunoregulatory states in AML. We investigated whether the MRC1 variants rs691005 and rs2253120 are associated with AML occurrence, development and prognosis.

We genotyped rs691005 and rs2253120 in 335 patients with AML and 326 healthy controls. Their associations with AML susceptibility, cytogenetic abnormalities, risk stratification, complete remission after two treatment cycles, and overall survival (OS) were examined under co-dominant, dominant, and recessive models. Independent prognostic effects were assessed using multivariable Cox regression. The relationship between SNP and MRC1 expression was evaluated using GTEx eQTL data and genotype-stratified expression measurements in primary AML bone marrow CD34⁺ cells. TCGA datasets were used to assess MRC1 expression and survival in AML. Virtual MRC1 knockdown and pathway analysis was performed using a single-cell RNA-sequencing dataset generated at our center.

Neither variant was associated with AML susceptibility, cytogenetic abnormalities, or early remission. rs691005 was associated with adverse risk stratification and showed a nominal association with shorter OS in Kaplan-Meier analysis. rs2253120 AA homozygosity was associated with improved OS after multivariable adjustment and was linked to lower MRC1 expression in GTEx and primary AML samples. Higher MRC1 expression was associated with poorer OS in TCGA-LAML. Virtual MRC1 knockdown revealed exploratory enrichment patterns related to myeloid differentiation, adhesion, cytokine production, and immune regulation.

MRC1 rs691005 was linked to adverse risk stratification and shorter OS, whereas rs2253120 AA homozygosity was independently associated with better OS and lower MRC1 expression. These findings support a potential role for inherited variation at the MRC1 locus in the clinical and immune heterogeneity of AML.

Exercise can modulate immune function and inflammatory signaling in cancer populations; however, its effects on the immune system in men with localized prostate cancer undergoing active surveillance are unknown. This study examined the effects of high-intensity interval training (HIIT) on circulating immune cell phenotypes, function, and systemic cytokine levels in this clinical setting.

This was a secondary analysis of the Exercise During Active Surveillance for Prostate Cancer (ERASE) trial, a single-center randomized controlled trial. Fifty-two men with localized prostate cancer on active surveillance were randomized to a 12-week supervised aerobic HIIT program (n=26) or usual care (n=26). HIIT consisted of three sessions per week at 85% to 95% of peak oxygen consumption. Fasting blood samples were collected at baseline and post-intervention. Changes in immune cell subsets (T cells, B cells, and NK cells; flow cytometry), NK cell cytotoxicity, and plasma cytokine concentrations were assessed. Analyses of covariance were used to compare between-group differences.

The HIIT group attended 96% of prescribed sessions. Compared with usual care, the HIIT group showed a significant increase in the proportion of the circulating major NK-cell subset (CD3-CD56+CD16+) (adjusted between-group difference, 2.0%; 95% CI, 0.3 to 3.7; p=0.024) and PBMC-mediated cytotoxicity against K562 (2.9%; 95% CI, 0.3 to 5.4; p=0.031). A significant between-group decrease was also observed in basophil counts (-0.04 ×10⁹/L; 95% CI, -0.07 to -0.01; p = 0.011), with no differences in other leukocyte populations. HIIT significantly reduced plasma levels of IL-4 (-0.02 pg/mL; 95% CI, -0.03 to -0.01; p = 0.011) and IL-12p70 (-0.14 pg/mL; 95% CI, -0.23 to -0.06; p = 0.002) compared with usual care. No significant between-group differences were observed in T cell or B cell subsets, or other inflammatory cytokines including IL-6 and TNF-α.

A 12-week supervised HIIT program significantly increased the proportion of the circulating major NK-cell subset and PBMC-mediated cytotoxicity while reducing IL-4 and IL-12p70 concentrations in men with prostate cancer undergoing active surveillance. Because these were peripheral-blood measures rather than tumor-level readouts, and given the exploratory design and number of comparisons, these findings should be interpreted as hypothesis-generating and require confirmation in larger, adequately powered studies.

Cervical nodal metastasis critically influences prognosis in oral squamous cell carcinoma (OSCC), yet current staging does not quantify the degree of metastatic replacement within lymph nodes. This study evaluated morphometric index Node Deposit Size Index (NDSI) to assess their association with pathological aggressiveness and survival.

An ambispective cohort of 104 surgically treated, node-positive OSCC patients was analysed. Maximum metastatic deposit diameter and lymph node diameter were measured on routine H&E slides. NDSI correlated with clinicopathological variables, extranodal extension (ENE), lymph node density (LND), and survival using non-parametric tests, Spearman correlation, Kaplan-Meier analysis, and ROC curves.

ENE-positive nodes demonstrated higher NDSI than ENE-negative nodes (86.9% vs 43.8%; p < 0.001). NDSI increased across pathological nodal stage (pN), from 31.9% in pN1 to 87.8% in pN3b (p < 0.001), and across overall stage, reaching 87.9% in Stage IVB (p < 0.001). Higher NDSI was associated with lymphovascular invasion (LVI) (72.0% vs 45.4%; p < 0.001) and perineural invasion (69.5% vs 50.7%; p = 0.024). NDSI correlated with LND (Spearman ρ=0.43, p < 0.001). ROC analysis identified an NDSI cutoff of 73.3% for predicting ENE (AUC = 0.854; not internally validated) and a cutoff of 60% for predicting 1-year mortality (AUC = 0.708; not internally validated). On multivariable linear regression (R² = 0.524), LVI and pN (pN2a, pN2b, and pN3b) were independently associated with higher NDSI, whereas the remaining clinicopathological variables were not independently significant.

NDSI correlate with adverse pathology and early mortality. However, the association between NDSI and ENE is not fully independent of pathological N-stage, and reproducibility, independent prognostic value, and cutoff stability require external validation before clinical use.

Although central nervous system leukemia (CNSL) is a recognized complication of acute leukemia, myelodysplastic neoplasms (MDS) complicated by CNSL are exceedingly rare, particularly after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies have largely focused on chronic myelomonocytic leukemia with central nervous system (CNS) involvement. Here, we describe the first comprehensively documented case of isolated CNS infiltration after allo-HSCT in a patient with MDS.

A patient with high-risk MDS with increased blasts-2, harboring IDH1 and TP53 mutations, a complex karyotype, and a very high Molecular International Prognostic Scoring System score underwent unrelated allo-HSCT. On day +19 post-transplantation, the patient developed a severe, unexplained headache. Cerebrospinal fluid (CSF) analysis by flow cytometry revealed blasts largely immunophenotypically consistent with those in the bone marrow at initial diagnosis, while concurrent bone marrow assessment confirmed remission. CSF blasts were cleared following triple intrathecal therapy (IT). To date, the patient remains in remission on azacitidine maintenance therapy, with an overall survival of 14 months from diagnosis.

Although CNSL is exceptionally rare in patients with MDS, this case demonstrates that isolated CNS infiltration may occur after allo-HSCT. Our findings emphasize that CNS involvement should be considered in the differential diagnosis of patients with MDS presenting with neurological manifestations, even without marrow relapse. Furthermore, this case highlights the critical role of CSF flow cytometry in establishing the diagnosis when conventional CSF studies are inconclusive.

Osteosarcoma (OS) is an aggressive primary bone malignancy that predominantly affects children and adolescents. Although surgery and chemotherapy have improved survival, therapeutic progress has remained limited over recent decades. Aberrant fatty acid metabolism has been increasingly implicated in OS progression, yet its distribution across different cellular compartments of the tumor microenvironment remains unclear. In this study, we integrated single-cell RNA-sequencing data from 140,562 cells across 17 OS patients and characterized the metabolic heterogeneity of tumor microenvironment. Two fatty acid metabolism-associated populations were identified: IBSP+ malignant osteosarcoma cells and SPARC+ macrophages. IBSP+ malignant cells showed preferential activation of fatty acid degradation and occupied an intermediate state along the pseudo-time trajectory. Lipid uptake and cholesterol efflux programs reached their highest activity near this state, indicating substantial lipid metabolic remodeling along the inferred transition among malignant-cell states. By contrast, SPARC⁺ macrophages exhibited a lipid-adapted, immunosuppressive phenotype accompanied by elevated fatty acid degradation activity. Cell-cell communication analysis further identified IBSP⁺ malignant cells as a major source of APOE- and SPP1-related signals directed toward SPARC+ macrophages, suggesting coordinated metabolic communication between these populations. To evaluate its clinical relevance, we applied transcriptomic deconvolution to independent OS cohorts. Concurrent enrichment of IBSP+ malignant cells and SPARC+ macrophages was associated with significantly shorter overall survival. Comparison of the double-high and double-low groups subsequently identified DKK1 as a candidate effector linked to this adverse metabolic niche. Consistent with this observation, DKK1 silencing in MG-63 cells reduced proliferation, colony formation, migration, and invasion. Collectively, these findings characterize fatty acid metabolism-associated cellular heterogeneity and a clinically relevant association between IBSP⁺ malignant cells and SPARC⁺ macrophages in OS, while identifying DKK1 as a candidate prognostic and therapeutic factor associated with the double-high phenotype.

Endometrial, ovarian, and cervical cancers differ substantially in epidemiology, anatomy, and unmet clinical need, yet the same inorganic nanomaterial toolbox is often discussed without disease-specific translational context. This narrative review synthesizes preclinical and clinical literature on gold, magnetic, mesoporous silica, carbon-based, and metal-organic framework nanotheranostic platforms identified through PubMed and Web of Science searches from database inception through August 2026, using a structured comparison across endometrial, ovarian, and cervical cancer. Particular attention is given to biosafety, reproductive toxicity, patient-derived organoid (PDO) models, AI-assisted design, manufacturing, and regulatory translation. Clinically, carbon nanoparticle suspensions have direct evidence for sentinel lymph node mapping in endometrial cancer, whereas the strongest ovarian cancer precedents for locoregional and nanomedicine delivery remain non-inorganic, including hyperthermic intraperitoneal chemotherapy and pegylated liposomal doxorubicin. In cervical disease, organic hexaminolevulinate photodynamic therapy for CIN2, approved by China's NMPA in March 2026, provides a relevant local drug-device comparator. We identified no inorganic nanomedicine currently approved specifically for a gynecologic malignancy; ferumoxytol is approved as an intravenous iron replacement product, and AuroLase gold nanoshells remain investigational, with no gynecologic trial identified. Route-matched delivery - intrauterine or hysteroscopic for endometrial cancer, intraperitoneal for ovarian cancer, and topical or intracervical for cervical disease - may therefore be more clinically relevant than increasing platform complexity alone. EC- and OC-derived organoids provide increasingly mature disease models that could support nanotherapeutic screening, but direct nanomedicine validation remains limited, while AI-assisted design is constrained by small heterogeneous datasets and limited external validation. Future progress will depend on reproductive-safety endpoints, appropriately validated PDO models, standardized manufacturing and characterization, and regulatory strategies that clearly distinguish established evidence from preclinical promise.

Ovarian cancer (OC) is a type of gynaecological cancer with a higher mortality rate due to diagnosis at an advanced stage and limited treatment options. This study aimed to leverage transcriptomic data to identify cellular and molecular pathways and potential anti-cancer compounds that specifically target primary invasive epithelial ovarian cancer (EOC). By employing next-generation knowledge discovery (NGKD) methodologies, we sought to unravel the intricate molecular landscape of primary invasive EOC using RNA sequencing (RNA-seq) data and decipher potential therapeutics for this debilitating disease. We performed NGKD analysis of the Gene Expression Omnibus (GEO) dataset GSE1295399 obtained from whole RNA-seq experiments. Using the raw counts and filtered metadata from GEO, we identified 2123 differentially expressed genes (DEGs) based on a Log₂ fold change (≤ ±0.6) and a p-value cutoff of < 0.05, between primary invasive EOC and benign EOC using the ExpressAnalyst platform. The DEGs were further analysed using both ExpressAnalyst and WebGestalt tools for differentially regulated cellular and molecular pathways and gene ontology (GOs), including biological process (GO-BP), molecular function (GO-MF) and cellular components (GO-CC). Both L1000 Fire Works Display (L1000FWD) and L1000 Characteristic Direction Signature Search Engine (L1000CDS2) tools were used to decipher synthetic or natural chemical compounds with the potential to reverse OC-associated gene signatures. DEGs implicated in key cellular and molecular pathways, such as oxidative phosphorylation, cell cycle, proteasome, programmed cell death protein-1 (PD-1) signalling, nuclear factor kappa B (NF-kB) signalling, cytokine and chemokine signalling, natural killer cell-mediated cytotoxicity and microRNAs in cancer, were positively enriched. The ribosome, translation, translational initiation and elongation and transforming growth factor-beta (TGF-β) signalling were negatively enriched in primary invasive EOC. Based on NGKD analysis, we identified approximately 50 synthetic or natural compounds, including naproxol, palbociclib, etoposide, wortmannin, PP-110, AZD-8055, amsacrine and BRD-K6595526. The results of this study could aid in the development of personalized treatment plans based on the unique profile of each tumour type, thus facilitating the development of personalized or precision treatment plans and improving diagnostic and prognostic capabilities in the clinic. In conclusion, the combination of RNA-seq and cutting-edge NGKD methodologies holds significant promise for identifying key cellular and molecular pathways and OC therapeutics.

Naringenin, a prominent member of the flavanone family of polyphenols, is widely distributed in cherries, tomatoes, and citrus fruits, such as grapefruits, as well as in medicinal plants. In vitro and in vivo investigations have shown that naringenin, naringenin-loaded nanoparticles, and its derivatives, whether administered singularly or in conjunction with other anticancer agents, can effectively counteract carcinogenic agents and inhibit the advancement of various malignancies, including colon cancer, lung neoplasms, ovarian cancer, and breast cancer. In this study, the effects of naringenin-benzylpiperazines (3b, 3f, and 3g) were investigated on breast ductal carcinoma MCF7 (ER-α+), human breast adenocarcinoma SK-Br, human triple-negative breast metastatic adenocarcinoma MDA-MB-231, ovarian cancer NIH-OVCAR-3, and human ovarian cancer SKOV-3 cells. The IC₅₀ values of 3b, 3f, and 3g were found to be between 31.39 and 73.60 µM, 29.11 and 86.91 µM, and 23.53 and 88.63 µM, respectively. The data obtained indicate that compound 3f may be a molecule with the potential to trigger mitochondrial apoptosis in cancer cell lines in a dose-dependent manner by modulating hypoxia, angiogenesis, and JAK/STAT signaling pathways. In addition, the potential therapeutic value of the compound and its interaction mechanisms with molecular targets have been investigated through theoretical (in silico) calculations.

Giant cell fibroma (GCF), a benign fibrous growth, accounts for about 4.7% of all oral benign or reactive fibrous growths. GCF commonly occurs in Caucasians, with a minor female predilection and a peak occurrence in the first three decades of life. Clinically, gingival nodules that are roughly 1 cm in diameter are commonly seen. Diagnosis relies on histopathological features, as clinical features are not sufficient on their own.

Here, we report Egyptian case series of three female and two male patients with GCFs, with age range from 15 to 64 years. Three of them occurred in relatively uncommon locations (tongue and buccal mucosa). Some of the patients had esthetic concerns and others had masticatory problems. The first case was multiple, which is extremely rare. The lesions were removed surgically and depending on the histopathological features, a final diagnosis of giant cell fibroma was established.

It is crucial for dentists to identify GCFs due to their frequent occurrence and to consider them when making a differential diagnosis with other fibrous hyperplastic diseases of the oral cavity, not only solitary lesions but also multiple lesions.

To better understand primary acinic cell carcinoma (AcCC) of the breast, this study investigated its clinical and pathological features.

Nine cases of primary acinic cell carcinoma were thoroughly evaluated using routine pathological and immunohistochemical methods. The clinical features, pathological morphological features, and prognosis of each case were collected and analyzed.

The tumors were located in the left breast in four cases (44.4%) and the right breast in five (55.6%). Most lesions (88.9%, 8/9) were in the upper outer quadrant, with one (11.1%) in the lower outer quadrant. One case (11.1%) was categorized as BI-RADS 6, and eight (88.9%) as BI-RADS 4. Histologically, the cases exhibited diverse growth patterns. The predominant patterns were microglandular and acinar. Less common patterns included microcystic, cystic, follicular, clear cell, and solid structures. Eosinophilic secretions were visible within the lumens.The tumor cells showed cytoplasmic variations (granular, clear, or basophilic) and prominent nucleoli. Immunohistochemically, all tumors were negative for estrogen receptor (ER) and androgen receptor (AR). Progesterone receptor (PR) was weakly positive in two cases and negative in the remaining seven. Human Epidermal Growth Factor Receptor 2 (HER2) immunohistochemistry was negative in five cases and scored 1 + in four. Alpha-1-antichymotrypsin (AACT) was positive in four cases, while lysozyme was positive in eight. Collagen IV was negative in all cases, whereas epithelial membrane antigen (EMA) was diffusely positive. S100 protein expression was detected in seven cases. Notably, all cases exhibited an mutant-type p53 expression pattern, and the Ki-67 proliferation index ranged from 5% to 80%.

AcCC of the breast is a rare, triple-negative malignancy that typically presents as a BI-RADS 4 lesion in the upper outer quadrant. Its diagnosis is based on characteristic morphological features-primarily microglands and acinar patterns, along with less common cystic, follicular, clear cell, and solid architectures. This is supported by a distinctive immunohistochemical profile, which consistently includes mutant-type expression of p53 protein. A comprehensive understanding of the clinicopathological and immunophenotypic spectrum of AcCC is crucial for accurate diagnosis and differential diagnosis. Enhanced recognition of this entity, particularly its rare morphological variants, will help reduce diagnostic errors and guide more precise clinical management, ultimately improving prognostic assessment for affected patients.