In this paper, we report a case of sequential immune-related adverse events induced by envafolimab in a patient with small cell lung cancer (SCLC), including immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM), diabetic ketosis (DK), and pneumonitis (CIP). A 63-year-old male with limited-stage SCLC received 4 cycles of etoposide plus carboplatin chemotherapy followed by radiotherapy, concurrent with maintenance immunotherapy using envafolimab. Eight months after initiating immunotherapy, the patient developed symptoms of dry mouth and excessive thirst. The clinical presentation was consistent with ICI-DM, though all diabetes-associated autoantibodies were negative. After achieving glycemic control with insulin, envafolimab was resumed. At 15 months, metastasis to the left submandibular region was identified and managed with localized iodine-125 seed implantation; envafolimab monotherapy was continued as maintenance treatment. Nineteen months after initiation of immunotherapy, the patient presented with chest tightness, shortness of breath, and dyspnea. Further diagnostic evaluation confirmed CIP and radiation pneumonitis, which improved following glucocorticoid therapy. Envafolimab was consequently suspended, and topotecan therapy was initiated for one month as second-line therapy, but was ultimately discontinued due to financial constraints. Six months after discontinuing topotecan, the patient was readmitted due to a progressively enlarging left submandibular metastases. Laboratory findings upon admission revealed DK, which had occurred due to self-discontinuation of insulin and a switch to oral hypoglycemic agents one week ago. During hospitalization, recurrent syncope of unknown origin occurred. After clinical improvement with supportive care, anti-tumor therapy with anlotinib was initiated as third-line therapy. Following envafolimab immunotherapy, the patient sequentially developed ICI-DM, DK and CIP. With prompt intervention, severe complications such as diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state, and respiratory failure were successfully avoided. This case underscores the importance of early recognition and management of immune-related adverse events (irAEs). The occurrence of DK after self-discontinuation of insulin highlights the necessity for long-term insulin therapy in ICI-DM. The patient remains alive with an overall survival exceeding 27 months, suggesting that ICI-DM may represent a potential prognostic biomarker for favorable outcomes in patients receiving immunotherapy.

The efficacy of immune checkpoint inhibitors (ICI) combined with chemotherapy as a neoadjuvant/adjuvant therapy for locally advanced penile squamous-cell carcinoma (PSCC) remains unclear.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract, with its pathogenesis primarily linked to activating mutations in the KIT or platelet derived growth factor receptor alpha (PDGFRA) genes. Surgical resection remains the standard curative treatment for localized GIST; however, ~50% of patients eventually develop recurrence or metastasis. Since the introduction of imatinib in the early 21st century, the management of metastatic GIST has shifted from solely surgical intervention to a systemic, chronic disease management model centered on tyrosine kinase inhibitors (TKIs). However, during the course of treatment, most patients develop drug resistance. Despite the transformative impact of TKIs, some critical clinical challenges remain unresolved. Intratumoral heterogeneity, in particular, poses a significant obstacle, as tumors often comprise diverse populations of cells with varying genetic and molecular profiles. This diversity means that while some subclones may initially respond well to TKI therapy, others harboring inherent or acquired resistance mutations can continue to proliferate, ultimately leading to treatment failure. Additionally, the limited durability of TKIs responses, even in tumors initially sensitive to treatment, remains a pressing concern. Moreover, the lack of curative systemic options for advanced GIST, along with adverse drug reactions, underscores the unmet needs within this patient population. These challenges underscore the necessity of this review, which discusses current standard drug treatment strategies for advanced GIST, including sequential TKIs therapy and investigations into mechanisms of drug resistance. Finally, the review explores precise and actionable future directions for GIST drug development and clinical management, including mutation-stratified therapeutic sequencing, rational TKI-based combination regimens, and circulating tumor DNA (ctDNA)-guided real-time treatment monitoring and resistance surveillance.

To evaluate the efficacy, safety, and treatment burden of intravitreal ranibizumab (RBZ) combined with a dexamethasone (DEX) intravitreal implant compared to ranibizumab monotherapy for macular edema (ME) secondary to non-ischemic retinal vein occlusion (RVO).

Previous research has demonstrated the effectiveness of lenvatinib and programmed death-1 (PD-1) blockades in the treatment of sarcoma. However, there is limited information regarding the efficacy and safety of combining lenvatinib with PD-1 blockades as a re-challenge therapy in patients with metastatic soft tissue sarcoma (STS) following prior treatment failure with tyrosine kinase inhibitors (TKIs).

Skp1 is a potential pharmacological target for cancer treatment. However, the few Skp1 inhibitors reported to date have exhibited limited structural diversity and target specificity. This highlights the need for new chemical scaffolds that could potentially be developed into potent and specific Skp1 inhibitors.

Triple-negative breast cancer (TNBC) is prone to relapse and metastasis due to the immunosuppressive state of the tumor microenvironment and limited exposure to relevant antigens, and chemotherapy alone has poor efficacy. We have developed a novel theranostic nanoplatform to address these problems: multifunctional nanocapsules (NCs) with a PD-L1-mediated gold shell induce immunogenic cell death (ICD) to remodel the immune microenvironment. PD-L1 and NLG919 dual immune checkpoints are programmed to synergistically sensitize photothermal therapy and chemotherapy, and photoacoustic imaging (PAI) is used to visualize and localize TNBC tissues for identification.

breast cancer remains a significant global health burden, with chemotherapy serving as a cornerstone of treatment. However, chemotherapy is associated with a high symptom burden, adversely impacting patients' quality of life. This study assessed the prevalence, severity, and impact of symptom burden among breast cancer patients undergoing chemotherapy in Delta State, Nigeria.

Cisplatin is a widely used chemotherapeutic agent; however, its therapeutic efficacy is often limited by severe cytotoxic side effects, particularly gastrointestinal toxicity, which manifests as intestinal mucositis. MicroRNAs (miRNAs) are small non-coding RNAs that play critical roles in both normal physiological and pathological processes by regulating gene expression. However, their role in cisplatin-induced gastrointestinal toxicity remains unclear. In this study, we investigated the regulatory effects of miRNAs on cisplatin-induced inflammation in intestinal epithelial cells (IEC-6). Our results demonstrate that cisplatin significantly decreases cell viability while inducing interleukin-6 (IL-6) expression in a dose-dependent manner. Moreover, we observed that cisplatin activates the phosphorylation of p38 and ERK but does not activate JNK in IEC-6 cells. Using specific inhibitors of p38 and ERK, we confirmed their roles in regulating IL-6 expression. Through analysis of the miRNA database, we identified several miRNAs that potentially target IL-6. Notably, rno-let-7f-5p and rno-let-7g-5p showed significant downregulation following cisplatin treatment. Transfection mimics and inhibitors of rno-let-7f-5p and rno-let-7g-5p further confirmed their regulatory role in IL-6 expression. Importantly, inhibition of the p38 and ERK pathways attenuated the cisplatin-induced reduction of rno-let-7f-5p and rno-let-7g-5p levels, suggesting a potential regulatory link between MAPK signaling and miRNA expression. In conclusion, our findings support a model in which cisplatin promotes inflammation in intestinal epithelial cells by activating the p38 and ERK pathways and is associated with the suppression of rno-let-7f-5p and rno-let-7g-5p. These findings provide mechanistic rationale that may inform future efforts to mitigate cisplatin-associated gastrointestinal toxicity.

The aggregation-caused quenching (ACQ) phenomenon limits the bioimaging application of traditional fluorescent probes. To address this, we developed a novel strategy to convert ACQ-type bioactive Staurosporine analogues into aggregation-induced emission (AIE) luminogens by constructing a donor-acceptor system via the introduction of cyano units as strong electron-withdrawing groups. First, we successfully developed a novel fluorescent scaffold based on the skeleton of Staurosporine, which is a kind of microbial secondary metabolite. Next, we synthesized three derivatives (STY1-3) by introducing a new rotor via one-step structural modification. These three compounds exhibited tunable AIE fluorescence and retained significant bioactivity. Cellular imaging demonstrated their capacity to outline cell contours with low background interference, while cytotoxicity assays revealed potent antitumor activity against NCI-N87 and MCF-7 cell lines. This work provides a design method for developing bioactive AIE probes from natural ACQ scaffolds.

Restoring apoptosis in malignant cells represents a central goal of anticancer therapy. Tumour cells often escape cell death by overexpressing anti-apoptotic members of the BCL-2 protein family, particularly BCL-2, BCL-xL, and MCL1. These proteins inhibit the intrinsic mitochondrial apoptotic pathway through intricate interactions with pro-apoptotic partners and direct modulation of the mitochondrial outer membrane. Their pivotal role in cell survival has established them as attractive therapeutic targets. Over the past two decades, significant efforts have been devoted to developing selective small-molecule inhibitors capable of neutralising these proteins and reactivating apoptosis. A first milestone was the discovery of ABT-263 (navitoclax), a dual BCL-2/BCL-xL inhibitor. Building on this achievement, the development of venetoclax, a highly selective BCL-2 inhibitor, marked a major breakthrough, demonstrating potent pro-apoptotic activity and clinical efficacy in several leukaemia subtypes. Despite these advances, the design of inhibitors of BCL-2 family members remains challenging, largely due to the structural characteristics of the BH3-binding groove, which is both shallow and hydrophobic, complicating the identification of molecules with optimal binding affinity and selectivity. PROTACs targeting BCL-xL may represent a promising future strategy, potentially overcoming the intrinsic limitations of small molecule inhibitors.

Folate-conjugated PLGA-PEG nanocarriers have emerged as a promising strategy for targeted delivery of anticancer agents such as 9-bromo-noscapine (9-Br-Nos) for targeting of folate receptors, which are overexpressed in breast cancer cells. They were synthesized and characterized for their size, morphology, encapsulation efficiency, and drug release profile. In vitro cytotoxicity studies have revealed an enhancement in anticancer efficacy of nano-formulated drugs compared to free drugs. Enhanced cellular uptake, improved mitochondrial membrane potential, and increased reactive oxygen species (ROS) production were observed in treated cells. Additionally, the spheroid disintegration assay was performed to evaluate the effect of the nano-formulation on the three-dimensional (3D) tumor model. Western blot analysis revealed changes in the expression of apoptosis-related proteins, further supporting the enhanced therapeutic potential of the nanocarrier system. In vivo pharmacokinetic studies demonstrated improvement in bioavailability and prolonged circulation of the nano-encapsulated drug. This study underscores the potential of nanocarrier-based drug delivery systems in improving the therapeutic efficacy of anticancer agents.

BACKGROUND Methotrexate-induced encephalopathy is an uncommon but potentially serious neurotoxic complication of high-dose methotrexate therapy. Its clinical and radiological features can closely resemble acute ischemic stroke, leading to diagnostic confusion and unnecessary interventions. Early recognition is crucial to prevent mismanagement and ensure appropriate care. CASE REPORT We report a 16-year-old girl with high-grade osteosarcoma of the distal femur who developed sudden neurological symptoms, beginning with dysphasia and cognitive slowing, progressing within 1 hour to global aphasia and altered consciousness following high-dose methotrexate infusion. Laboratory findings were normal. Magnetic resonance imaging performed 2 hours after symptom onset revealed bilateral diffusion restriction in the centrum semiovale, without corresponding fluid-attenuated ınversion recovery (FLAIR) abnormalities, suggestive of acute ischemia. Intravenous thrombolysis with alteplase (0.9 mg/kg) was administered, but subsequent imaging showed shifting diffusion abnormalities without vascular occlusion, inconsistent with stroke. Methotrexate was withheld, and supportive care alone led to complete neurological recovery within 3 days. The patient resumed chemotherapy 1 week later and remained asymptomatic at 1-year follow-up. CONCLUSIONS Methotrexate-induced encephalopathy is an important stroke mimic in oncology patients. Diffusion restriction without FLAIR changes and a reversible clinical course help distinguish it from true ischemic stroke. Awareness of this condition is essential, as full recovery can occur with supportive care alone, without the need for specific therapeutic interventions.

The excellent biocompatibility and tunable optical properties of carbon dots make them highly promising for applications in photodynamic therapy (PDT). However, effectively enhancing their photodynamic performance remains a significant challenge. This work employed methylene blue and metformin as precursors along with three trace metal elements ion (Fe3+, Zn2+ and Cu2+) to synthesize carbon dots (CDs, FeCDs, ZnCDs and CuCDs) via a one-step hydrothermal method.

The menin-lysine methyltransferase 2A acute leukemia (KMT2A) protein-protein interaction has emerged as a clinically validated epigenetic target in acute leukemia, following the approval of the reversible menin inhibitor Revumenib for KMT2A-rearranged and nucleophosmin 1 (NPM1)-mutant disease. This success transformed a once "undruggable" interface into a tractable binding pocket, triggering the rapid expansion of medicinal-chemistry strategies aimed at achieving deeper and more durable transcriptional reprogramming. This review analyzes the full menin-inhibitor landscape from a medicinal-chemistry perspective, integrating reversible, covalent, and degrader-oriented modalities within a unified structure-activity framework. We highlight how scaffold architecture, pocket occupancy, electrophile placement toward Cys329, and polarity tuning control binding mode, residence time, metabolic stability, resistance susceptibility, and pharmacodynamic durability. Across all chemical classes, sustained target engagement-rather than equilibrium affinity alone-emerges as the dominant determinant of antileukemic efficacy. By integrating structure-activity relationship (SAR), resistance mechanisms, safety considerations, and translational scope across oncology and metabolic indications, this review provides a roadmap for the rational design of next-generation menin inhibitors and establishes menin as a model system for modern epigenetic drug discovery.

Marine organisms are considered as a reservoir of diverse metabolites with unique skeletons and multifaceted biological activities. Marine organisms, including Xenia, Cespitularia, and Heteroxenia, have been extensively studied in recent decades to explore their activities. Species of the genus Heteroxenia play a robust ecological role and afford a wide array of metabolites, including steroids, sesquiterpenoids, diterpenoids, and lipid derivatives with notable bioactivities as cytotoxic, antiviral, antimicrobial, and anti-inflammatory properties primarily based on in vitro studies. Fourteen compounds were isolated and their structures were elucidated based on NMR data and mass spectrometry. Most of these metabolites possess rare or uncommon structural frameworks such as gorgostane- and androstane-type steroids, and verticillane diterpenoids with an unusual C-6/C-12 skeleton, which are infrequently reported from marine sources. This review provides a comprehensive overview of Heteroxenia corals, highlighting their ecological role, metabolites isolated from Heteroxenia species, with emphasis on their 13C NMR spectroscopic features and reported bioactivities. This integrative approach provides a chemotaxonomic spectroscopic framework and identifies research gaps, that support future natural product discovery and pharmacological investigations of Heteroxenia species, while acknowledging that ecological function and general bioactivity do not necessarily predict direct therapeutic applicability and require further validation of selectivity and safety.

Immune checkpoint inhibitors (ICIs) targeted PD-1/PD-L1 axis generate immune-related adverse events such as myocarditis, limiting their clinical application. Herein, we tried to explore the potential mechanism of ICIs-induced myocarditis. We performed single-cell RNA sequencing of heart tissues and peripheral blood mononuclear cells (PBMC) collected from mice with or without a relative low dose of PD-1/PD-L1 inhibitor (BMS-1) treatment. Compared with PBS treatment, BMS-1 treatment increased T, B, NK cells, and neutrophils but decreased macrophages in the heart. Four T cell subclusters in the heart were identified, including Treg, LEF1+CD4+ T, CCL5+CD8+ T, and STMN1+CD8+ T cells. The BMS-1-heart exhibited increased CCL5+CD8+ T cells depicted by elevated Nkg7 and Ccl5 gene expression compared with the PBS-heart. The number of macrophages declined but revealed inflammatory activity in the BMS-1-heart. Interestingly, CCR5, a receptor for CCL5 expressed in both CCR2- resident and CCR2+ recruit macrophages in the heart, was upregulated by the BMS-1 treatment. In addition, fibroblasts, not endothelial cells, showed an inflammatory activation state. Last, we identified increased CCL5+CD8+ T cells in the BMS-1-PBMC. Immunofluorescence staining also confirmed significantly elevated CCL5+CD8+ T cells in the BMS-1-heart than that of PBS-heart. BMS-1 seems to recruit circulating CCL5+CD8+ T cells to the heart, which further interact with CCR5+ macrophages, resulting in fibroblast activation. The CCL5/CCR5 axis and circulating CCL5+CD8+ T cells may be potential therapeutic/diagnostic strategies for ICIs-induced myocarditis.

3-Mercaptopyruvate sulfurtransferase (3-MST), a key enzyme in sulfur metabolism, has recently gained attention as a potential anticancer target. However, reported 3-MST inhibitors remain limited, motivating the exploration of new scaffolds such as natural products. In this study, a library of 3744 natural products was virtually screened against human 3-MST using DiffDock (diffusion-model-based docking) followed by AutoDock Vina docking. Top-ranking candidates were further analyzed via molecular dynamics simulations and Molecular Mechanics Poisson-Boltzmann Surface Area binding free energy calculations. Methylophiopogonanone A (4), Daphnoretin (5), and L-asarinin (9) exhibited stable binding with favorable energetics, displaying binding free energies comparable to the reference ligand 7NC301. Binding mode analyses revealed that Methylophiopogonanone A primarily engaged in hydrophobic interactions, whereas Daphnoretin and L-asarinin formed extensive polar contacts, accompanied by higher desolvation penalties. In vitro cytotoxicity assays showed that Methylophiopogonanone A and L-asarinin reduced HCT116 cell viability by 40.3% and 26.3% at 25 µM, which is consistent with their inhibitory of 3-MST with IC50 = 5.83 ± 0.69 µM and IC50 = 19.11 ± 3.37 µM, respectively. These results suggested that the natural products identified in this study represent promising scaffolds for further optimization as potential 3-MST inhibitors. This work provides an AI-guided natural-product screening workflow for 3-MST and delivers prioritized inhibitor scaffolds for subsequent optimization and experimental validation.

Geraniol (GI), an acyclic monoterpene alcohol, exhibits diverse anti-cancer activities. However, its potential effects against gastric cancer remain poorly understood.

To assess the incidence of delayed chemotherapy-induced nausea and vomiting (CINV) and identify key risk factors among adult patients.