The aim of this study is to develop nanocomposites consisting of near-infrared nanoparticle-functionalized metal-organic frameworks and investigate their antitumor performances. Using molybdenum disulfide and 30% H2O2 as reactants, novel near-infrared molybdenum oxide nanoparticles (HxMoO3 NPs) were synthesized via supercritical fluid technology. A one-pot method was then employed to synthesize doxorubicin-loaded metal-organic framework nanocomposites and molybdenum oxide nanoparticles (DOX/HxMoO3@ZIF-8 NPs). The morphology and structure of the DOX/HxMoO3@ZIF-8 were characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), energy dispersive spectroscopy (EDS), and thermogravimetric analysis (TGA). The obtained DOX/HxMoO3@ZIF-8 exhibited a uniform crystal structure, high drug-loading of 45.5 mg/g, large specific surface area (311.9 m2/g), and excellent photothermal conversion efficiency (79.6%). The in vivo studies showed that mice in the DOX/HxMoO3@ZIF-8 + NIR group exhibited the smallest tumor size (22.3 ± 9.2 mm2) and the lightest tumor weights (0.02 ± 0.005 g), significantly demonstrating its in vitro and in vivo antitumor activity. These findings suggest that the developed nanocomposite has hight potential for enhancing the application of multifunctional nanocarriers in tumor treatment.

Doxorubicin is an antitumor antibiotic. It is often used in veterinary medicine to treat and extend the lives of dogs with cancer. A cardiotoxic side effect can lead to heart failure and treatment discontinuation. This systematic review and meta-analysis aimed to evaluate the drug's cardiotoxic effects on the ejection fraction (EF) of dogs in doxorubicin protocols. The search was done in eight databases, with a total of 3587 articles screened, resulting in fifteen eligible articles included. A report on the included studies' methods and results was done. It also assessed the risk of bias. Thirteen articles demonstrated cardiac changes in echocardiography with different routes of administration (intravenous and intracoronary). The intracoronary route was more toxic, and in all six studies performed, there was heart failure. The intravenous route caused heart failure in six of the nine studies. A meta-analysis showed this drug worsened heart disease. It included four studies where it significantly lowered the EF. Overall, the intervention produced a mean reduction of 21.24% in EF. This review shows doxorubicin's impact on cardiac function. It reveals the need for careful monitoring of each patient.

IntroductionFor many years, 5-fluorouracil (5-FU) has been utilized as a chemotherapeutic treatment for a variety of malignancies. Unfortunately, 5-FU causes cardiotoxicity, which restricts its clinical use. Nifuroxazide (NFX) is a STAT-3 inhibitor with antioxidant and anti-inflammatory effects.MethodsCardiotoxicity was induced by 5-FU (30 mg/kg) once daily for 5 days. NFX was administered in two doses, 25 and 50 mg.ResultsCompared to 5-FU-control rats, NFX significantly attenuates cardiotoxicity induced by 5-FU, as indicated by decreasing creatine kinase (CK)-MB, aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) serum levels. Histopathological examinations confirmed the protective effects of NFX against histological abrasions induced by 5-FU. NFX attenuated the oxidative damage induced by 5-FU mediated by peroxisome proliferator-activated receptor gamma (PPAR-γ) signal activation. Moreover, NFX mitigated 5-FU-induced inflammation by suppressing nucleotide-binding domain, leucine-rich repeat-containing protein 3/signal transducer and activator of transcription 3 (NLRP3/STAT3) signal activation. Notably, these protective effects are dose-dependent. Additionally, NFX mitigated 5-FU-induced apoptosis by downregulating Bax, while upregulating Bcl-2.ConclusionsCollectively, NFX attenuated 5-FU-induced cardiac intoxication by regulating NLRP3/STAT-3, PPAR-γ, and Bax/Bcl-2 signals.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have improved cancer outcomes but can induce immune-related adverse events, including mycobacterial infections. This study retrospectively analysed pulmonary nontuberculous mycobacteria (NTM) infection in 91 patients with pre-existing stage II-IV lung cancer at Shanghai Pulmonary Hospital between June 2015 and June 2024. Among these patients, 78.0% [71/91] were male, and 16.5% [15/91] were receiving ICIs monotherapy at the time of initial pulmonary NTM infection diagnosis (ICIs group). Compared with the non-ICIs group, ICIs-treated patients developed pulmonary NTM infection earlier (median time: 12 months [IQR, 6-18] vs. 21.5 months [IQR, 13-30]; p = 0.004), and had a higher proportion of rapid-growing NTM isolates (73.3% [11/15] vs. 30.3% [23/76]; p = 0.003), predominantly Mycobacterium abscessus complex (40.0% [6/15]). In contrast, Mycobacterium avium complex was the predominant NTM species in the non-ICIs group (71.1% [54/76]). During 12 months of anti-NTM therapy, the ICIs group showed a lower cumulative sputum culture conversion rate (36.4% [4/11] vs. 59.6% [31/52]; p = 0.19) and a longer median time to initial sputum culture conversion (12 months vs. 6 months; p = 0.13), though these differences were not statistically significant. The most commonly administered ICIs drugs were tislelizumab (40.0% [6/15]) and sintilimab (26.7% [4/15]). These findings suggest that ICIs may be associated with earlier development of pulmonary NTM infection in lung cancer patients. Future prospective studies with larger sample sizes are needed to validate this conclusion.

Marine-derived fungi have emerged as a promising source of bioactive compounds with therapeutic potential. This study investigates the biological activities of Aspergillus niger MF6, a fungal isolate derived from coral reefs along the Hurghada coast in the Red Sea, Egypt. The isolate demonstrated significant antimicrobial activity, with broad-spectrum inhibition against pathogens, including E. coli, S. aureus, and C. albicans, achieving inhibition zones up to 20 mm. Ethyl acetate was identified as the most effective solvent for extracting bioactive compounds, facilitating the isolation of metabolites responsible for antimicrobial activity. Antioxidant assays revealed robust activity, with dose-dependent scavenging effects across multiple mechanisms. Furthermore, cytotoxicity assays against HepG-2 and MCF-7 cancer cell lines demonstrated moderate cytotoxic activity, with IC50 values of 177.25 ± 5.42 µg/ml and 256.97 ± 7.45 µg/ml, respectively. GC-MS analysis identified key bioactive compounds, including hexadecenoic acid and 9-octadecenoic acid, likely contributing to these effects. This study underscores the therapeutic promise of coral-associated fungi as a sustainable source of antimicrobial, antioxidant, and anticancer agents.

Tislelizumab, a PD-1-targeting monoclonal antibody, can potentially treat advanced esophageal squamous cell carcinoma (ESCC). Using pooled clinical data, this study evaluates Tislelizumab's efficacy and safety in advanced ESCC.

Brain tumors, particularly gliomas, are among the most lethal malignancies, with high mortality driven by a delayed diagnosis and limited therapeutic efficacy. A central challenge lies in the presence of the blood‑brain barrier (BBB), which severely impedes the delivery of systemically administered therapeutics to tumor sites. Addressing this clinical urgency, nanoparticle (NP)‑based delivery systems have emerged as a transformative strategy to enhance brain‑specific drug accumulation, minimize off‑target toxicity and improve treatment outcomes. The present review systematically examined the recent advances in nanocarrier technologies for targeted brain tumor therapy, including liposomes, solid lipid NPs, dendrimers, polymeric nanoplatforms and inorganic nanomaterials. The design principles, mechanisms for BBB traversal, therapeutic payload compatibility and tumor‑targeting capabilities of NP technologies demonstrated in preclinical models have also been highlighted. In addition to drug delivery, emerging applications of nanocarriers in gene therapy were explored and the impact of protein corona formation on NP behavior in vivo was discussed. Finally, current translational bottlenecks were identified and future design considerations to achieve clinically viable, precision‑targeted nanomedicines for brain tumors were outlined.

This study investigates the green synthesis of selenium nanoparticles (SeNPs) and their encapsulation in liposomes as a novel drug delivery system to enhance the antibacterial and anticancer properties of SeNPs. Liposomes are well-known for their ability to improve the biological activity of encapsulated drugs, making them a promising candidate for targeted therapies, particularly in oral cancer treatment.

Copper nanoparticles (CuNPs) have received interest due to their antibacterial, antioxidant, and anticancer effects. However, current synthesis methods frequently use harmful substances. Green synthesis with plant extracts provides a safer, more environmentally friendly option. This study looks at the production of CuNPs with Passiflora flower extract and assesses their biological activity.

The present demonstrated that SSL-CH extract selectively inhibits the growth of HeLa cell lines though activation of p53 and Bax genes medaied proapoptotic pathway signifying it is a potential alternative anticancer agent for cervical cancer.

To overcome the dual challenges of suboptimal therapeutic outcomes and delayed detection in hepatocellular carcinoma (HCC), a nucleus-targeting theranostic nanoplatform based on gadolinium-functionalized carbon dots (GdCDs) is presented. GdCDs were synthesized via a one-step hydrothermal method utilizing neutral red and citric acid as carbon precursors and gadolinium chloride hexahydrate as the paramagnetic source, showing good fluorescence (FL) and magnetic resonance imaging (MRI) capabilities. After modified with a nuclear localization sequence (NLS), GdCDs were loaded with doxorubicin (DOX) to yield the integrated theranostic platform: Nucleus-targeting gadolinium-functionalized carbon dot drug delivery system (NT-GdCDs-DDS) for FL/MRI dual-modality imaging and nucleus-targeting drug delivery. NT-GdCDs-DDS exhibited optimal excitation/emission wavelengths at 497/596 nm, a high longitudinal relaxivity (r1) of 23.11 mM-1 s-1, and a DOX loading efficiency of 61.9%. Results of antitumor activity assays in vitro demonstrated the viability of HepG2 cells incubated with 400 μg/mL NT-GdCDs-DDS for 24 h was 8.12%, demonstrating strong antitumor activity. Furthermore, a significant tumor growth suppression in mice was observed by treated with NT-GdCDs-DDS over a 15-day period, showing superiority to free DOX. These findings establish NT-GdCDs-DDS as a potent theranostic nanoplatform for simultaneous HCC imaging and therapy.

Chrysin (CHR), a naturally occurring flavonoid with promising anticancer potential, suffers from poor water solubility, limiting its therapeutic applications. To address this, β-Cyclodextrin (β-CD) inclusion complexes (ICs) of CHR were synthesized via the freeze-drying method at varying molar ratios (1:1, 1:2, 1:3, 1:4), with the 1:4 ratio exhibiting the highest entrapment efficiency (95.23%) and selected for further study. These ICs were then functionalized onto gold nanoparticles (AuNPs) to develop CHR-β-CD-AuNPs, enhancing drug delivery and stability. Characterization by UV-Vis, FTIR, NMR, NTA, and TEM confirmed successful encapsulation, hydrogen bonding, and spherical morphology with an average particle size of ~ 43 nm. Molecular docking supported strong interactions between CHR and β-CD. In vitro studies against human triple-negative breast cancer (MDA-MB-231) cells demonstrated that CHR-β-CD-AuNPs exhibited potent cytotoxicity with an IC50 of 22.17 ± 1.24 mg/L, significantly lower than CHR/β-CD ICs (IC50: 22.84 ± 1.00 mg/L) and free CHR (IC50 > 100 mg/L, p < 0.001). Hoechst and phalloidin staining revealed clear apoptotic features such as nuclear fragmentation and cytoskeletal disruption. Gene expression analysis showed upregulation of Bax and Caspase-3 and downregulation of Bcl-2, confirming apoptosis induction. Furthermore, scratch wound assays demonstrated significant inhibition of cancer cell migration, with wound closure reduced to 8.38 ± 0.74% (IC) and 15.27 ± 1.05% (IC-AuNPs) compared to 74.41 ± 1.22% in untreated controls (p < 0.001). These findings establish that β-CD-based CHR-AuNP nanocarriers substantially improve the solubility, stability, and therapeutic efficacy of CHR, offering a promising nanoformulations strategy for enhanced targeted breast cancer therapy.

Most drug discovery studies use 2D cell cultures and animal models for screening new chemical entities (NCEs), which often leads to suboptimal results due to genetic variations, species differences, or lack of most physiological preclinical models. This is one of the most important reasons behind high rate of failure of drug candidate in the clinic, especially in oncology drug development projects. To address this issue, we developed a 3D pancreatic tumor spheroid model that better mimics the parental tumor architecture. We observed similar drug effects on cellular viability in both 2D cultures and 3D spheroids. However, cellular viability alone is insufficient to predict the translation of efficacy into clinical studies. A 3D multicellular tumor model is essential to comprehensively evaluate drug effects on the tumor microenvironment (TME), angiogenesis, and tumor biomarkers. Our model includes 3D monocellular and multicellular spheroids, which demonstrated a more relevant platform for potency evaluation. We used pancreatic ductal adenocarcinoma cells PANC-1 and PANC04.03 to conduct a comprehensive drug screening and assessed spheroid shrinkage and pre-vascularization. We also evaluated RT-qPCR analysis for gene expression of CSC markers (CD44, SOX2, KRT18), EMT markers (αSMA, vimentin) and the apoptotic marker (Annexin A1) under various conditions. Our findings highlighted the significant differences between 2D and 3D cultures, underscoring the importance of 3D multicellular models for predicting therapeutic markers and enabling comprehensive drug evaluation. In this study, MRTX1133 (a Phase I candidate of KRAS-G12D inhibitor) was used for testing our hypothesis. Treating the spheroids with MRTX1133 revealed enhanced drug response profiles compared to 2D cultures. This study underscores the critical importance of 3D multicellular model in preclinical drug screening and their potential to bridge the gap between in vitro studies and clinical outcomes.

This study investigated the effects of peach gum polysaccharide (PGP) on chemotherapy-induced intestinal injury and behavioral changes in mice. Female C57BL/6 mice were injected with E0771 breast cancer cells and divided into 3 groups: control, chemotherapy (pirarubicin), and PGP treatment (pirarubicin plus PGP). Behavioral tests, colon length measurement, tissue staining, 16S rDNA sequencing, and metabolomics were performed. Transcriptomic data of colon and hippocampal tissues were analyzed and validated by Western blotting. PGP significantly alleviated colon damage, reduced inflammation and apoptosis, and restored colon length. It mitigated depressive behaviors by suppressing inflammasome activation in the hippocampus, increased gut microbiota diversity, and improved depression-associated metabolites. After the depletion of the intestinal flora, the antidepressant effect of PGP is significantly weakened. These findings suggest that PGP protects against chemotherapy-induced intestinal and behavioral damage by modulating the gut microbiota and gut-brain axis.

The B-cell lymphoma-2 (Bcl-2) family proteins, key regulators of apoptosis, are frequently dysregulated in cancer, tipping the balance of cell survival and apoptosis in favor of survival. The ubiquitin-proteasome system (UPS) is a critical cellular machinery that controls the Bcl-2 levels through regulation of protein stability. This review delves into the intricate interplay between the proteasome and Bcl-2 family members, exploring how proteasome-mediated degradation impacts cell survival and proliferation to influence cancer progression. We discuss the therapeutic potential of targeting the proteasome-Bcl-2 axis, including the use of proteasome inhibitors as anticancer agents. We examine their mechanisms of action, clinical efficacy, and limitations while exploring emerging strategies to overcome these challenges.

The CXCR4/CXCL12 axis is vital for tumor metastasis and immune evasion in various cancers. However, developing effective inhibitors is challenging due to complex intracellular interactions and limitations of soluble receptor drugs targeting single transmembrane proteins. Here, we engineered a water-soluble CXCR4QTY-Fc molecular trap by fusing a redesigned CXCR4 variant with the IgG1-Fc domain. CXCR4QTY-Fc effectively neutralizes CXCL12, inhibits CXCR4 downstream signaling, and suppresses migration and invasion of CXCR4-positive cancer cells in vitro, even with dipeptidyl peptidase 4 (DPP-4) inhibition. In mouse models of pancreatic, breast, and prostate cancer metastasis, CXCR4QTY-Fc significantly reduced tumor metastasis, outperforming the clinical CXCR4 antagonist AMD3100. Mechanistically, CXCR4QTY-Fc blocks endosomal CXCL12/CXCR4 signaling and reshapes the tumor microenvironment by downregulating CXCL12, thereby inhibiting tumor growth, metastasis, and angiogenesis. This biomimetic, non-immunogenic approach offers a promising strategy for broad-spectrum metastasis inhibition.

Chemotherapy is one of the first-line treatment options in cancer patients. Cisplatin (CDDP) is widely used as one of the antineoplastic agents in many cancers. Nevertheless, CDDP resistance is considered as a therapeutic challenge in cancer. Considering the CDDP side effects in normal tissues, prediction of CDDP response helps to select a suitable therapeutic strategy in cancer patients. Sex-determining region Y-box 2 (SOX2) is a critical regulator of tumor growth and embryogenesis that is involved in tumor metastasis, apoptosis, and cell proliferation, through association with other developmental/oncogenic signaling pathways. SOX2 has also a crucial role in CDDP resistance in tumor cells. Therefore, we discussed the role of SOX2 in regulation of CDDP response in tumor cells. It has been reported that SOX2 upregulation through PI3K/AKT, WNT, Hippo, and TGF-β signaling pathways mainly promotes the CDDP resistance in tumor cells. The present review can be an effective step in introducing SOX2 as a prognostic marker as well as a therapeutic target in cancer patients.

Sweet's syndrome is also called as acute febrile neutrophilic dermatosis. Drug-induced Sweet's syndrome was first reported in association with trimethoprim-sulfamethoxazole. It is very rare. To the best of our knowledge, bleomycin-induced Sweet's syndrome has not been reported previously.

3-Phosphoglycerate dehydrogenase (PHGDH) is a key enzyme in the serine biosynthesis pathway, supporting cancer cell growth, survival, and proliferation. Its overexpression is frequently observed in aggressive cancers such as breast cancer, melanoma, and glioma, where it drives tumor growth, metastasis, and resistance to oxidative stress. Targeting PHGDH with small-molecule inhibitors has emerged as a promising therapeutic strategy. Notable inhibitors like NCT-503, CBR-5884, Azacoccone E, and Ixocarpalactone A, along with covalent inhibitors such as Withangulatin A, exhibit potent anticancer activity by limiting serine availability and inducing apoptosis. Gene-silencing techniques, including RNA interference (RNAi) and CRISPR/Cas9, further validate PHGDH as a therapeutic target. Advances in computational methods and structure-activity relationship (SAR) analysis have accelerated the discovery of selective PHGDH inhibitors, offering insights into binding mechanisms and facilitating rational drug design. However, cancer cells can activate alternative metabolic pathways, such as glutaminolysis, to evade PHGDH inhibition. Thus, combination therapies targeting multiple metabolic nodes are being explored to enhance efficacy and overcome resistance. Ongoing research focuses on optimizing PHGDH inhibitors through virtual screening, QSAR modeling, and clinical trials, aiming to integrate them into precision oncology and develop effective therapies for patients with high PHGDH expression or specific metabolic profiles.

Metastasis is one of the leading factors of cancer-related deaths worldwide. New potential targets and treatment strategies are needed to extend survival and enhance the quality of life for these patients. We performed an in-depth bioinformatics analysis to identify potential genes and associated potential therapeutic compounds for metastasis of prostate adenocarcinoma. The differentially expressed genes (DEGs) were first identified using four datasets (GSE8511), (GSE3325), (GSE27616) and (GSE6919) present in the Gene Expression Omnibus (GEO) database and analyzed using the GEO2R. WGCNA was performed to find a significant gene cluster. Network analysis was performed using MCODE and Cytohubba plugins of Cytoscape to select hub genes. Moreover, expression validation of key genes was carried out using the TCGA dataset. Functional annotation and pathway enrichment analyses were conducted for validation, while survival analysis was applied to assess potential therapeutic effects. DEGs retrieved from the GEO were submitted to the Connectivity Map database to identify potentially related compounds. Molecular docking, ADMET analysis and drug-likeness properties, MD simulations and MM-GBSA analysis were performed to screen for the best potential drugs. We identified three compounds-Prunetin, Ofloxacin, and ALW-II-49-7 that may help extend disease-free survival in patients with tumor metastasis. Additionally, ACTA2, MYLK, and CNN1 were recognized as potential therapeutic targets for these compounds. These drugs' potential effectiveness and binding efficiency were screened using induced fit molecular docking followed by 100 ns MD-based Simulations and MM-GBSA analysis. However, further in vitro and in vivo studies are needed to confirm these findings. Insight box This study integrates microarray gene expression profiling with bioinformatics tools to identify differentially expressed genes (DEGs) and co-expression networks using WGCNA. Network analysis in Cytoscape was used to screen hub genes, and the Connectivity Map (cMAP) database was searched for potential candidate drugs. Binding efficiency of repurposed drugs was evaluated using molecular docking, molecular dynamics (MD) simulations, and MM-GBSA analysis. Our findings provide the potential therapeutic drugs and targets of prostate adenocarcinoma metastasis with possibilities for follow-up in vitro and in vivo validation.