Pancreatic cancer is highly aggressive with limited treatment options. PLA2G16 has been implicated in cancer progression, but its role in prognosis and gemcitabine sensitivity in pancreatic cancer remains poorly understood.

Immune Checkpoint Inhibitor-related Pneumonitis (CIP) exhibits high morbidity and mortality rates in the real world, often coexisting with pneumonia, particularly after immunochemotherapy. We aimed to develop and validate a non-invasive nomogram for differentiating CIP from pneumonia in patients undergoing immunochemotherapy.

Immune checkpoint inhibitors (ICI)-containing therapy for advanced or recurrent non-small cell lung cancer (NSCLC) are not completed by some responders for reasons other than progressive disease (PD). The proportion of patients who discontinue ICI and the length of their treatment-free status are unclear.

Extracellular vesicles (EVs) is promising in predicting the efficacy of immune checkpoint inhibitor (ICI) therapies. But it is challenging to determine the level of circulating EVs due to their variations in spatial and temporal distribution. To address this, we developed an in situ EV detection platform integrating multiplex EV capture with microfluidic-generated immune-tumor spheroids. This platform enables in situ monitoring of EV secretion dynamics under ICI and chemotherapeutic treatments, capturing localized and temporal changes in EV release. Using predictive models, we identified EVs carrying programmed cell death ligand 1 (PD-L1) as the most robust predictors of spheroid viability during treatment. RNA sequencing further revealed that dynamic EV expression changes are driven by gene transcription, providing a temporal understanding of EV regulation. Our platform overcomes the limitations of traditional methods by offering a physiologically relevant system to study EV-mediated immune responses. By addressing the spatial and temporal heterogeneity of EVs, this work advances EV-based biomarker discovery and provides a foundation for optimizing personalized immunotherapies.

Triterpenoid compounds such as betulinic acid (BA) and oleanolic acid (OA) exhibit considerable pharmacological activities. However, their current production primarily relies on plant extraction and chemical synthesis, methods that are often plagued by low efficiency, complex extraction processes, and environmental concerns. Microbial-based synthesis has emerged as one of the most effective approaches for producing BA and OA.

Colorectal cancer (CRC) has emerged as a global health concern, as evidenced by its position as the second leading cause of cancer-related mortality. This underscores the necessity for effective disease management strategies. The present study aims to assess the impact of chitosan nanoparticles (CSNP) conjugated with the Lactobacillus acidophilus secretome (CSNP/L.a-sup), on the signaling pathways associated with CRC.

Triple-negative breast cancer (TNBC) is associated with a poor prognosis due to insufficient molecular subtyping precision and limited actionable targets. Although metabolic reprogramming underlies TNBC chemotherapy resistance, establishing metabolic subtyping systems and investigating drug sensitivity across distinct metabolic subgroups could provide novel therapeutic avenues for breast cancer management. GSVA (Gene Set Variation Analysis) analysis of metabolic pathways reveals significant differences in TNBC (Triple-Negative Breast Cancer) patients. TNBC patients are classified into four metabolic subtypes through consensus clustering, based on their GSVA values of metabolic pathways. These subtypes are: MS_1, characterised by increased lipogenic activity; MS_2, characterised by increased carbohydrate and nucleotide metabolism; MS_3, a metabolism-active subtype with activation of all types of metabolism; and MS_4, characterised by suppressed metabolic activity across all types of metabolism. We next propose a novel method called MODIN (Multiomics-Driven Drug-Cell Interaction Network), which embeds multi-omics gene information (mRNA expression, copy number variation and DNA methylation) and drug SMILES data into a latent space, and then employs a multi-head attention-based interaction module to accurately predict the LN_IC50 values of 621 drugs in TNBC. Based on MODIN, noteworthy disparities in drug sensitivity emerge between the patient cohorts categorised as MS_2 and MS_3. MS_3 patients show a significantly higher sensitivity to chemotherapy regimens, especially for doxorubicin and docetaxel, while the MS_2 cohort displays marked resistance to these drugs. Our study reveals the metabolic heterogeneity of TNBC, and TNBC patients with increased carbohydrate and nucleotide metabolism exhibit the poorest prognoses and greater resistance to doxorubicin and docetaxel.

The advancement of nanotechnology and the growing demand for environmentally sustainable processes have fueled interest in green synthesis methods. In this research, copper-doped zinc oxide nanoparticles (Cu: ZnO NPs) were synthesized using a microwave-assisted approach, employing a bio-extract derived from Pistia Stratiotes (PS) leaves as a reducing agent. Comprehensive characterization through UV-Visible spectroscopy, PL, FTIR, SEM with EDS, TEM, DLS, XRD and XPS confirmed the formation, optical and structural features of the synthesized NPs. SEM and TEM images revealed spherical and nanorod-like morphologies, with particle sizes ranging from 15 nm to 65 nm and a tendency to agglomerate. Density Functional Theory (DFT) simulations using Quantum Espresso indicated a band gap narrowing to 3.0 eV after copper doping. Biologically, the Cu: ZnO NPs exhibited strong antibacterial activity against Candida albicans (16.3-17.5 mm), Staphylococcus aureus (18.4-21.5 mm), and Escherichia coli (19-21.6 mm). Additionally, the NPs showed promising anticancer potential against SK-MEL-28 melanoma cells, with an IC50 value of 30.53 µg/mL. Overall, this research demonstrates an eco-friendly and efficient route for fabricating Cu: ZnO NPs with significant antimicrobial and anticancer properties, emphasizing their potential for future biomedical applications.

The present study reports, the eco-friendly synthesis of gold nanoparticles (AuNPs) using Equisetum diffusum D. Don. extract, a medicinal plant known for its therapeutic properties. Phytochemicals present in the extract served as reducing and stabilizing agents for synthesizing stable AuNPs with an average size range of 68.8 nm. The biosynthesized AuNPs were characterized using UV-vis spectroscopy, FTIR, XRD, SEM, EDX, and dynamic light scattering (DLS) methods, confirming their stability, morphology, and crystalline nature. The green synthesized ED@AuNPs exhibited promising biological activities, including broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria, with inhibition zones from 24 to 37 mm. The anticancer activity was assessed through an MTT assay against hepatic carcinoma (HePG2) cells, revealing dose-dependent cytotoxicity with maximum inhibition at 200 µg/mL (47.62%). Antidiabetic activity was demonstrated by starch hydrolysis and enzyme kinetics, with significant α-amylase inhibitory activity up to 70.85%, comparable to the standard drug Acarbose. Moreover, antioxidant activity was conformed through FRAP and DPPH assays, indicating strong free radical scavenging activity and reducing ability. The study demonstrates the potential of biosynthesized ED@AuNPs as multifunctional agents with applications in biomedicine, particularly in antibacterial, anticancer, antidiabetic, and antioxidant therapies, offering an eco-friendly and sustainable approach for nanoparticle synthesis.

Hepatocellular carcinoma (HCC) presents a significant global health challenge, marked by high mortality and recurrence. This study investigated the synergistic potential of cisplatin and palbociclib (C + P) against HCC cell lines. RT-qPCR revealed that C + P significantly downregulated HCC-related genes, including Hsp90, β-catenin, and components of the PI3K/AKT/mTOR pathway, compared to cisplatin alone and controls. Western blotting confirmed a reduction in phosphorylated AKT (P-AKT) with palbociclib and C + P, while PTEN, a tumor suppressor, was upregulated in the C + P group. Annexin V-FITC assays demonstrated a substantial increase in apoptosis in palbociclib and C + P treated cells. Cell cycle analysis indicated S and G0-G1 phase arrest with C + P, suggesting a combined cytotoxic effect. Scratch wound assays showed that both palbociclib and C + P significantly inhibited cell migration compared to cisplatin and controls. These findings suggest a promising synergistic effect of C + P in overcoming cisplatin resistance in HCC. However, further research is needed to fully elucidate the complex interactions between these drugs.

Recent clinical trials have demonstrated that neoadjuvant administration of PD-1 + /- CTLA-4 inhibitor is superior to adjuvant PD-1 inhibitors in patients with resectable stage III and IV cutaneous melanoma. However, the generalizability of these results to an unselected patient population treated in routine clinical settings remains unclear.

Despite the use of therapeutic modalities such as surgery, chemotherapy, and radiotherapy, breast cancer remains a potentially fatal condition for humans. The primary problems with these treatments are their low efficacy and their inevitable side effects to the surrounding healthy tissues. Overcoming these challenges has been achieved through precision therapeutics, where personalized interventions have significantly improved treatment efficacy. However, the development of nanoparticles has largely remained focused on optimizing delivery platforms based on a one-size-fits-all approach. As lipid-based, polymeric, and inorganic nanoparticles are now being engineered with greater specificity, they are increasingly suited for customization-paving the way for truly personalized drug delivery in the era of precision medicine. In this line, the current study focuses on breast cancer, and recent developments in drug delivery. The first part of this review looks at practical difference between precision medicine and precision targeting. It describes breast cancer signaling pathways, highlighting the exciting potential of nanotechnology in cancer drug delivery using precision targeting - an approach closely linked to precision medicine. We also go over how nanostructures can improve the way drugs, genes, and immunotherapy are delivered in the treatment of breast cancer. Lastly, we discuss challenges, solutions, future directions, and possibilities for the practical use of nanotechnology in the treatment of breast cancer, while introducing nano-products based on clinical trials.

An interesting sunlight-driven photodynamic therapy (PDT) has been realized. In this study, we propose a strategy involving an intramolecular electron-donating ligand to develop a high-performance type-I photosensitizer. Specifically, an electron-rich core is flanked by two iridium atoms, facilitating electron transfer and promoting hydroxyl radical generation. The resulting Ir(III) photosensitizer, Q-T, boosts the rapid generation of reactive oxygen species (ROS) under low-intensity laser exposure. Moreover, the type-I ROS ideally suits hypoxic microenvironments, thus demonstrating remarkable PDT against various cell lines, under artificial and natural sunlight. In a skin squamous carcinoma (A431) organoid model, one cycle of treatment of dosing of Q-T followed by sunlight irradiation effectively induces cellular apoptosis and completely eradicates tumor organoids. This approach offers a promising avenue for the efficient PDT of skin cancer utilizing sunlight.

The pathogenesis of uterine carcinosarcoma (UCS) remains unclear due to a few mature cell lines. Herein, we established a new cell line, ESCA, from a Chinese woman. Especially, three sublines, named ESCA-2, ESCA-3, ESCA-5, were isolated based on the rate of cells' different sedimentation. All ESCA cells have been subcultured for more than 60 generations. ESCA sublines display different cell morphology and growth characteristics, as well as have different sensitivity to chemotherapeutic drugs. ESCA was most sensitive to paclitaxel and carboplatin, while ESCA-2 was most sensitive to ifosfamide. Besides, ESCA showed severe chromosome karyotype abnormalities and abnormal number of chromosomes. Whole exome sequence showed ESCA and its sublines, as well as tissue block shared similar single nucleotide variants, such as TP53, TRRAP mutations, while relatively large differences in mutational signature abundance. When all ESCA cells were xenotransplanted subcutaneously into BALB/c-nu mice, they developed into tumors that resembled the original tumor with positive AE1/3 and Vimentin in immunohistochemical staining. Interestingly, the transplanted tumor from ESCA-5 proliferated fastest with a relatively low level of glucose uptake evaluated by micro-PET/CT scanning. Taken together, ESCA and its sublines may be valuable tools to explore the molecular mechanism of UCS.

The side effects and resistance to treatments associated with platinum compounds, such as cisplatin, underscore the present need for novel anticancer agents with improved properties. The development of hybrid drugs, combining two bioactive units, offers a promising approach by synergistically enhancing the biological activity of the two fragments while reducing the resistance of classic drugs. This work presents the synthesis of a novel family of heterobimetallic compounds, featuring a monofunctional Pt(II) complex with amino groups and a p-ferrocenylaniline ligand. Cytotoxic assays reveal that the derivatives with methylated and isopropylated substituted amines exhibit remarkably higher activity against several tumor cell lines compared with cisplatin and the unsubstituted diamino complex. Notably, these methylated and isopropylated complexes demonstrate high selectivity and present high antitumor activity in cell lines where cisplatin is ineffective. Classical molecular dynamics simulations targeting DNA reveal a consistent relation between the extent of distortion of the duplex upon complex coordination and the cytotoxic activity observed in biological assays. According to our simulations, coordination of the heterometallic complexes can produce a significant disruption of the H-bond pattern of the platinated guanine. Moreover, the distortion mechanism induced by the voluminous substituents of the amino ligands entails either the intercalation of the ferrocene moiety, facilitating new hydrogen bonds between originally non-interacting base pairs and new weak attractive stacking interactions between the Pt(II) complex and neighboring nucleobases, or the displacement of adjacent nucleotides from the pairing region toward the solvent environment.

Sustained increase in intraocular pressure (IOP) following intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) in the treatment of retinal disease has been theoretically attributed to aggregation of anti-VEGF in the iridocorneal angle. However, previous studies by our group showed full clearance of intravitreally injected bevacizumab, aflibercept, and ranibizumab. The objective of this study was to further analyze and compare the clearance of these anti-VEGF agents from the eye after a single injection in a rat model.

Gastric cancer is a common malignant tumour. Copper-induced cell death, a recently discovered form of metal ion-related cell death, has garnered significant attention from researchers. We synthesised a multifunctional nanoparticle, ZnO@CuEA, and characterised its morphology using transmission electron microscopy. Cytotoxicity was analysed via CCK8 assays and calcein-AM staining. The tumour-targeting capability of ZnO@CuEA was validated using confocal microscopy and in vivo imaging experiments. RNA-seq and proteomic analysis were conducted to assess changes in mRNA and protein expression before and after ZnO@CuEA treatment. Lysosomal β-galactosidase staining was employed for cellular senescence detection, and protein expression levels were analysed via Western blot. Finally, in vivo experiments demonstrated the tumour-inhibitory effect of ZnO@CuEA. ZnO@CuEA is a multifunctional nanoparticle capable of targeting tumour cells and inducing cuproptosis. In vivo experiments showed that ZnO@CuEA exhibits significant antitumor activity. The multifunctional nanoparticles synthesised in this study provide a novel therapeutic approach for cancer treatment.

The patient presents with a genetic condition named Li-Fraumeni syndrome, which predisposes her to multiple neoplasms during her lifespan. Due to the chemotherapeutic treatment of an osteosarcoma, the patient presents with cardiotoxicity secondary to doxorubicin that is refractory to conventional management. The patient is initially stabilized with a peripheral veno-arterial extracorporeal membrane oxygenation device, with no improvement after 14 days of support. Later she was assisted with a HeartMate 3 mechanical circulatory device as a bridge to candidacy or as a destination therapy. She is the first paediatric patient in Spain to be assisted with long-term circulatory support using the HeartMate 3 device.

VCP/p97 plays an important role in endoplasmic reticulum related degradation pathways, and inhibition of p97 was shown to induce ER stress and subsequently cell death in a variety of solid tumors and hematoma. For acute myeloid leukemia (AML) cells, inhibition of p97 activity leads to the accumulation of ubiquitylated proteins, activation of unfolded protein response (UPR) and apoptosis.

High-dose methotrexate (HD-MTX) is seen as an effective therapy for acute lymphoblastic leukemia (ALL); however, it is extremely toxic. Monitoring the plasma concentrations of methotrexate (MTX) and its important metabolite, 7-hydroxy-methotrexate (7-OH-MTX), on a routine basis aids in dose modification of rescue medications and in avoiding toxicity. The pharmacologically active and toxic effects of drugs are due to the unbound portion, as most drugs are bound to plasma proteins to some degree. However, the simultaneous measurement of unbound plasma concentrations of MTX and 7-OH-MTX has not been reported.