Twelve undescribed peptidic compounds, bukhansantaibols A-K (1-10) and bukhansantaibals A-B (11-12), were isolated from the soil fungus Trichoderma atroviride through LC-MS and bioactivity-guided purification. Their structures were elucidated by the analysis of 1D and 2D NMR spectra, HRESIMS, and acid hydrolysis using modified Marfey's method. All compounds were evaluated for their cytotoxic activity against HCT-8 (colon cancer) and SK-OV-3 (ovarian cancer) cells. Among them, compounds 1-5 exhibited significant inhibitory effects, with IC50 values ranging from 2.1 to 19.6 μM.

This paper explores a synthetic pathway for naphtopyrazolotriazines utilizing amines as versatile starting materials. The approach leverages the reactivity of amines to construct the triazine core, fused with naphtho and pyrazolo cycles, through a series of controlled diazo coupling and cyclization reactions. By employing amines, this method allows for the introduction of varied substituents, enabling the tailoring of electronic and steric properties to suit specific potential applications. The significance of this work lies in its efficiency, scalability, and potential to synthesize compounds with tunable functionalities. Naphtopyrazolotriazines are of interest due to the presence of a pyrazolo triazine moiety, which is known for its bioactivity, including anticancer and antimicrobial properties, and their possible utility in optoelectronic materials. All synthesized compounds have been characterized by 1D and 2D NMR, IR, UV-Vis, and mass spectrometry. Additionally, UV-Vis and fluorescence spectra of the synthesized compounds, together with the frontier molecular orbitals energies, were calculated by DFT methods implemented in Gaussian 09W software.

The human Poly ADP-ribose Polymerase (PARP) family comprises 17 enzymes responsible for the transfer of ADP-ribose to proteins, forming poly- or mono-ADP-ribosylation. This post-translational modification regulates DNA repair and programmed cell death, processes affecting cancer biology. PARP inhibitors, including the FDA-approved olaparib, are used to treat BRCA-dependent breast and ovarian cancers. Although therapies with use of PARP inhibitors are showing clinical success, their effects on the immune system remain understudied. Prior work has shown that PARP inhibition can modulate inflammatory responses and alter innate immunity. In this study, we evaluated the immunomodulatory effects of olaparib on myeloid cells in vivo, focusing on bone marrow and spleen. Olaparib treatment altered the composition and activation state of dendritic cells, neutrophils, and macrophages. In the bone marrow, olaparib increased the proportion of cDC2 population, mature neutrophils and inflammatory macrophages expressing CD80. In contrast, splenic myeloid cells exhibited enhanced expression of markers associated with tolerogenic phenotypes, including CD206 and CD124 in neutrophils and macrophages. The spleen also showed an increase in immature monocyte-derived dendritic cells (CD206+) and a bias toward the cDC2 subset. These findings indicate that PARP inhibition can induce short-term phenotypic remodeling of myeloid cell populations, promoting a more immunoregulatory profile, especially in the spleen. These changes may contribute to an altered immune landscape with implications for anti-tumor immunity.

Chemotherapy remains a cornerstone in the treatment of esophageal cancer (EC), yet chemoresistance remains a critical challenge, leading to poor outcomes and limited therapeutic success. Mitochondrial DNA (mtDNA) has emerged as a pivotal player in mediating these responses, influencing cellular metabolism, oxidative stress regulation, and apoptotic pathways. This review provides a comprehensive overview of the mechanisms by which mtDNA alterations, including mutations and copy number variations, drive chemoresistance in EC. Specific focus is given to the role of mtDNA in metabolic reprogramming, including its contribution to the Warburg effect and lipid metabolism, as well as its impact on epithelial-mesenchymal transition (EMT) and mitochondrial bioenergetics. Recent advances in targeting mitochondrial pathways through novel therapeutic agents, such as metformin and mitoquinone, and innovative approaches like CRISPR/Cas9 gene editing, are also discussed. These interventions highlight the potential for overcoming chemoresistance and improving patient outcomes. By integrating mitochondrial diagnostics with personalized treatment strategies, we propose a roadmap for future research that bridges basic mitochondrial biology with translational applications in oncology. The insights offered in this review emphasize the critical need for continued exploration of mtDNA-targeted therapies to address the unmet needs in EC management and other diseases associated with mitochondria.

This study aimed to compare adverse event (AE) profiles between Avastin and bevacizumab biosimilars to support clinical decision-making, given the limited availability of real-world data.

Spider silk is highly attractive material because of its superior mechanical properties and excellent biocompatibility, enabling it to self-assemble into a wide range of morphological structures for drug delivery system. However, most spider silk particles developed as drug carriers are based on complex repetitive domains of spider silk proteins and exhibit relatively large particle sizes (> 300 nm), which limits their biomedical applications. In this study, we engineered a novel recombinant spider silk protein (NC-iRGD) by integrating terminal domains derived from major ampullate silk and the tumor-penetrating peptide iRGD. The silk particles were generated by mixing with a high-concentration potassium phosphate buffer and exhibited an average particle size of approximately 170 nm, which is smaller than that of other reported spider silk particles. Under incubation of silk particles in the drug solution, a 90% loading efficiency for the peptide drug (ChMAP-28) were determined. The cytotoxicity result showed that NC-iRGD particles displayed excellent biocompatibility and high drug loading efficiency in the neutral pH and low ionic strength. The release of ChMAP-28 was shown to be dependent on the ionic strength and pH of the release buffer. Additionally, NC-iRGD demonstrated enhanced tumor penetration and greater cytotoxicity against cancer cells compared to NC particles due to its iRGD sequence. Overall, the high drug loading capacity, controlled-release capability, and improved tumor penetration of NC-iRGD particles make them a promising novel drug delivery system for targeting polypeptide therapeutics to tumor microenvironments.

This phase I trial aimed to assess the pharmacokinetics (PK), safety, and preliminary efficacy of a single dose of HR20013 (mixed formulation of fosrolapitant and palonosetron) plus dexamethasone in patients with malignant solid tumors.

Anticancer drug therapy-induced immunosuppression increases the incidence of treatment-resistant infectious diseases in cancer patients. Combining antibacterial and anticancer capabilities into a single medication can potentially enhance the treatment outcomes. In this light, the current study focused on developing innovative 5-arylidene-3-phenyl-2-thioimidazolones 1a-e and evaluated them as antimicrobial candidates against a panel of Gram-positive and Gram-negative bacterial and fungal isolates. Compounds 1e and 2d exhibited the most potent microbial activity, with MIC values ranging from 24 ± 0.5 to 12 ± 0.20 µg/ml in comparison with streptomycin and cycloheximide as reference standards. Using the colon cancer cell line (HCT 116) as a representative example, the novel compounds were assessed as anticancer agents. Compounds 1e and 2d appeared to be the most effective candidates, with IC50 values of 7.25 ± 1.03 and 44.3 ± 3.28 µg/ml, respectively, when compared to doxorubicin (IC50 = 4.12 ± 0.50 µg/ml). Therefore, we extended the anticancer study of both 1e and 3b to include the other three cancer cells, PC3, A549, and MCF-7, and the normal Vero cell line. 1e was the most effective anticancer compound, exhibiting IC50 values ranging from 5.2 ± 0.09 to 8.1 ± 0.11 µg/mL and demonstrating a promising safety profile against the BJ1 normal cell line. In vitro enzyme screening assay of 1e against CDK-2, EGFR, HER-2, and VEGFR-2 enzymes investigated its promising multitargeting inhibiting activity (IC50 = 0.314 ± 0.031, 0.183 ± 0.014, 0.197 ± 0.024, and 0.235 ± 0.028 µM, respectively). A molecular docking study was carried out to discover the probable interactions of compound 1e with the active sites of the assessed kinases. Additionally, in silico ADMET studies were carried out for 1e, which represented its good oral absorption, good drug-likeness characteristics, and low toxicity risks.

The aim of this research was to prepare a different particle sizes of zinc oxide nanostructures by two different methods. The zinc oxide nanoparticle (ZnO NPs) was successfully prepared by a green synthesis technique but the zinc oxide quantum dot (ZnO QDs) was successfully prepared by a chemical method. The structure, composition and morphology of the prepared different shapes of ZnO nanostructures have been characterized by the means of X-ray diffractograms (XRD), high resolution transmission electron microscope (HRTEM), Energy Dispersive x-ray (EDX), UV-Vis spectroscopy and Fourier transform infrared spectroscopy (FTIR). From UV-Vis spectroscopy studies we noticed that the optical band gap energy of ZnO nanostructures was decreased by increasing an irradiation time. The removal of complex organic contaminants and pollutants from water, the heterogeneous photocatalytic degradation of methylene blue (MB), Fluorescein and Rhodamine 6G (Rh 6G) dyes were studied using ZnO NPs and ZnO QDs as a derived catalyst. We had studied the impact of ZnO NPs and ZnO QDs as a catalyst to enhance the photocatalytic activity of different organic dyes under UV-Vis irradiation and we observed that the photodegradation percentage of organic dyes was rapidly increased by increasing UV irradiation time in both two shapes of ZnO nanostructures. ZnO QDs behave as the best photocatalyst for successfully photodegraded due to the smallest size of ZnO QDs has a higher photocatalytic activity than the large particle size of ZnO NPs. So, it is better to use the ZnO QDs as a removal dyes and pollutants in the wastewater application. Also, we have assessed the cytotoxicity of ZnO NPs and ZnO QDs against two cell lines, (T-47) breast cancer carcinoma, and (DU-145) prostate cancer cell compared to Human skin fibroblast (HSF). The proliferation of cancer cells using MTT assay clarified that both cancer cells (T-47), (DU-145) as well as (HSF) normal cell line are regularly inhibited as they grow on different concentrations of ZnQ QDs and ZnQ NPs. The maximum inhibitory effect of both were recorded at concentration of 100 µg/ml (62.63, 79.72 and 42.59% and 72.68, 83.28, 18.12 µg/ml) in case of ZnQ QDs and ZnQ NPs respectively. It was cleared that ZnQ NPs was more potent for test cancer cell lines, this was confirmed by IC50, since it was (18.12,13.3,74.86) in ZnO NPs compared with (42.59,17.05 and 76.4) in ZnQ QDs respectively. Finally, it was proved that the ZnO NPs behave as a good anticancer nanomaterial than ZnO QDs. This means ZnO NPs are superior for anticancer applications if compared with ZnO QDs.

Cancer is characterized by abnormal cell proliferation. Cyclins and cyclin-dependent kinases (CDKs) have been recognized as essential regulators of the intricate cell cycle, orchestrating DNA replication and transcription, RNA splicing, and protein synthesis. Dysregulation of the CDK pathway is prevalent in the development and progression of human cancers, rendering cyclins and CDKs attractive therapeutic targets. Several CDK4/6 inhibitors have demonstrated promising anti-cancer efficacy and have been successfully translated into clinical use, fueling the development of CDK-targeted therapies. With this enthusiasm for finding novel CDK-targeting anti-cancer agents, there have also been exciting advances in the field of targeted protein degradation through innovative strategies, such as using proteolysis-targeting chimera, heat shock protein 90 (HSP90)‍-mediated targeting chimera, hydrophobic tag-based protein degradation, and molecular glue. With a focus on the translational potential of cyclin- and CDK-targeting strategies in cancer, this review presents the fundamental roles of cyclins and CDKs in cancer. Furthermore, it summarizes current strategies for the proteasome-dependent targeted degradation of cyclins and CDKs, detailing the underlying mechanisms of action for each approach. A comprehensive overview of the structure and activity of existing CDK degraders is also provided. By examining the structure‍‒‍activity relationships, target profiles, and biological effects of reported cyclin/CDK degraders, this review provides a valuable reference for both CDK pathway-targeted biomedical research and cancer therapeutics.

Cancer immunotherapy targeting the PD-1/PD-L1 pathway has demonstrated efficacy across a range of common solid tumors and some hematopoietic malignancies. Despite these groundbreaking successes, the clinical development of other 'checkpoint inhibitors' targeting molecules like TIM-3, TIGIT, ICOS and others, has largely fallen short, often showing minimal clinical benefit even in combination with anti-PD therapy. This article explores three key hypotheses that help explain the disparity in therapeutic success: (1) the absence of tumor- specific immunosuppressive logic in many checkpoint targets, (2) the dominance-but not redundancy-of immune evasion mechanisms within the tumor microenvironment (TME), and (3) the emergence of therapy-induced resistance. This is not intended as a comprehensive review of the literature. Instead, it highlights select evidence to explain past failures and to illuminate a more strategic, biologically informed path forward.

Cancer is an age-related disease that affects one in two Japanese individuals, placing a significant burden on both patients and caregivers due to its clinical characteristics, high treatment costs, and associated adverse events (AEs). Consequently, cancer treatment remains a major public concern. In recent years, patient-centered medical care has gained increasing attention and is strongly desired in cancer treatment. Companion diagnostics (CDx) are expected to facilitate personalized treatment; however, their current status remains unclear. In this study, we evaluated the role of CDx in anticancer drug treatment based on data available at the time of drug approval. Our analysis revealed that the benefit-risk ratio, defined as the objective response rate of an anticancer drug divided by the incidence of severe AEs, was significantly higher for anticancer drugs requiring CDx (wCDx) in Japanese patients (1.54-fold, p < 0.0135) than for anticancer drugs not requiring CDx. Although the objective response rate did not differ between the 2 groups, the incidence of severe AEs was lower in the wCDx group. These findings suggest that CDx helps identify patients who are better suited for specific anticancer treatments and/or that active pharmaceutical ingredients in wCDx therapies carry a lower risk of severe AEs. To further promote patient-centered medical care, the active development of CDx alongside new anticancer drugs should be encouraged, despite the higher development hurdles, through regulatory support, particularly since drug pricing does not differ between the 2 groups.

Pigmentation is one of the most prominent side effects caused by anticancer drugs, especially in female patients, as these changes in appearance can decrease QOL. A typical drug causing such pigmentation is 5-fluorouracil (5-FU); we have previously shown that 5-FU-induced pigmentation is associated with increased adrenocorticotropic hormone (ACTH) and reactive oxygen species (ROS) levels. In male Hos:HRM-2 mice, 5-FU administration resulted in pigmentation appearing in the genital area, accompanied by elevations in neutrophils, ACTH, and ROS. By contrast, female mice showed increases in neutrophils and noradrenaline, but not in ACTH or ROS levels; furthermore, they did not develop pigmentation. In addition, estradiol levels were markedly decreased in female mice, which may have enhanced neutrophil apoptosis and suppressed ROS production. In addition, noradrenaline reflects the stress response and may contribute to the decrease in estradiol, suggesting the hypothalamus-pituitary-adrenal axis and sex hormones may interact in the formation of sex differences. These results suggest that sex differences exist in the development of 5-FU-induced hyperpigmentation and that fluctuations in estradiol and associated changes in neutrophils, ROS, and ACTH may underlie this phenomenon.

Chitosan, a naturally derived polysaccharide, has gained considerable attention as a biomaterial for drug delivery due to its excellent biocompatibility, biodegradability, and mucoadhesive properties. However, its limited solubility and compatibility with hydrophobic drugs restrict broader applications. Recent advances in the chemical modification of chitosan specifically through fluorination have significantly improved its performance in nanomedicine. Fluorinated chitosan (FCS) exhibits enhanced hydrophobicity, chemical and thermal stability, and improved drug encapsulation efficiency, making it highly effective for cancer therapy. This review comprehensively examines the synthesis techniques of FCS nanoparticles, such as grafting, ionic gelation, and microemulsion, and evaluates how these influence particle size, stability, and drug loading. The multifunctional role of FCS in targeted cancer drug delivery, photodynamic therapy, immunotherapy, and gene editing is critically analyzed, supported by in vitro and in vivo studies demonstrating improved tumor accumulation, cellular uptake, and immune modulation. Despite its promise, FCS presents challenges such as toxicity concerns and regulatory complexities, which must be addressed for clinical translation. Future prospects include developing stimuli-responsive systems and expanding FCS applications beyond oncology. Overall, FCS represents a transformative platform in nanotechnology, offering new avenues for precision drug delivery and personalized cancer treatment.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, with limited effective therapeutic options due to late diagnosis, aggressive progression, and rapid development of drug resistance. In pursuit of novel treatments, this study reports the design, synthesis, and biological evaluation of a new series of topsentin derivatives, featuring a 1,2,4-oxadiazole core. The newly synthesized derivatives were screened for antiproliferative activity against multiple PDAC cell lines (SUIT-2, Patu-T, and PANC-1), identifying several compounds with potent growth-inhibitory effects, particularly on SUIT-2 and Patu-T cells. Further studies demonstrated that these compounds also significantly inhibited cell migration and reduced clonogenic potential, with IC50 values in the micromolar range. The results suggest that these marine-inspired 1,2,4-oxadiazole derivatives effectively target key hallmarks of PDAC, including proliferation, migration, and colony formation, supporting their further development as promising candidates for overcoming drug resistance and metastatic progression in pancreatic cancer.

Microbial exopolysaccharides from extreme environments are increasingly becoming valuable candidates for drug development. In this study, four fractions named XL-1, XMRS-1, XL-1-D, and XMRS-1-D were isolated and purified from the hadal bacterium Psychrobacter pulmonis by column chromatography. The structural features of these fractions were characterized by molecular weight, monosaccharide composition, Fourier transform infrared (FTIR) spectrum, amino acid analysis and NMR. The results showed that XL-1 and XMRS-1 were mainly composed of mannose, glucose, and glucosamine, while XL-1-D and XMRS-1-D were mainly composed of mannose. In vitro bioactivity assays demonstrated that all four fractions significantly enhanced RAW264.7 macrophage proliferation and phagocytosis, stimulated nitric oxide (NO) and reactive oxygen species (ROS) production, and induced the secretion of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and the expression of inducible nitric oxide synthase (iNOS) mRNA. Moreover, plate cloning tests, cell scratch tests, and apoptosis assays, along with RT-qPCR analysis, demonstrated that the four fractions significantly inhibited A549 cells' proliferation. Specifically, XMRS-1 and XMRS-1-D upregulated Bax, Caspase-3, Caspase-8, and Caspase-9, while downregulating Bcl-2, suggesting transcriptional activation of apoptosis-related pathways. These results offered a reference for the further development and utilization of this hadal bacterium in the future.

Nudibranchs have garnered increasing interest in biomedical research due to their complex chemical defense mechanisms, many of which are derived from their diet, including sponges, cnidarians, tunicates, and algae. Their remarkable ability to sequester dietary toxins and synthesize secondary metabolites positions them as a promising source of biologically active compounds with potential therapeutic applications, particularly in oncology. This study aimed to review and summarize the available literature on the bioactive potential of nudibranch-derived compounds, focusing mainly on their antitumor properties. Although research in this area is still limited, recent studies have identified alkaloids and terpenoids isolated from species such as Dolabella auricularia, Jorunna funebris, Dendrodoris fumata, and members of the genus Phyllidia. These compounds exhibit notable cytotoxic activity against human cancer cell lines, including those from colon (HCT-116, HT-29, SW-480), lung (A549), and breast (MCF7) cancer. These findings suggest that compounds derived from nudibranchs could serve as scaffolds for the development of more effective and selective anticancer therapies. In conclusion, nudibranchs represent a valuable yet underexplored resource for antitumor drug discovery, with significant potential to contribute to the development of novel cancer treatments.

Neoxanthin is a xanthophyll carotenoid with high-value nutritional functions for human health due to its anti-cancer, anti-oxidative, and anti-obesity activities. In this present work, we systematically reviewed the structure, source, and biosynthetic pathways of neoxanthin, and discussed the advantages and disadvantages of the prevailing extraction methods of neoxanthin. Meanwhile, this review described the latest research progress on the pharmacological activities of neoxanthin. Finally, we concluded with a discussion on the main challenges of neoxanthin production from microalgae, and proposed some future development prospects and potential solutions.

The enzyme γ-glutamyl transpeptidase (GGT), located on the surface of cellular membranes, hydrolyzes extracellular glutathione (GSH) to guarantee the recycling of cysteine and maintain intracellular redox homeostasis. High expression levels of GGT on tumor cells are associated with increased cell proliferation and resistance against chemotherapy. Therefore, GGT inhibitors have potential as adjuvants in treating GGT-positive tumors; however, most have been abandoned during clinical trials due to toxicity. Recent studies indicate marine-derived ovothiols as more potent non-competitive GGT inhibitors, inducing a mixed cell-death phenotype of apoptosis and autophagy in GGT-overexpressing cell lines, such as the chronic B leukemic cell HG-3, while displaying no toxicity towards non-proliferative cells. In this work, we characterize the activity of two synthetic ovothiol analogs, L-5-sulfanylhistidine and iso-ovothiol A, in GGT-positive cells, such as HG-3 and HL-60 cells derived from acute promyelocytic leukemia. The two compounds inhibit the activity of membrane-bound GGT, without altering cell vitality nor inducing cytotoxic autophagy in HG-3 cells. We provide evidence that a portion of L-5-sulfanylhistidine enters HG-3 cells and acts as a redox regulator, contributing to the increase in intracellular GSH. On the other hand, ovothiol A, which is mostly sequestered by external membrane-bound GGT, induces intracellular ROS increase and the consequent autophagic pathways. These findings provide the basis for developing ovothiol derivatives as adjuvants in treating GGT-positive tumors' chemoresistance.

Colorectal cancer (CRC) remains a predominant cause of global cancer-related mortality, highlighting the pressing demand for innovative therapeutic strategies. Natural polysaccharides have emerged as promising candidates in cancer research due to their multifaceted anticancer mechanisms and tumor-suppressive potential across diverse malignancies. In this study, we enzymatically extracted a polysaccharide, named ERPP, from Ruditapes philippinarum and comprehensively evaluated its anti-colorectal cancer activity. We conducted in vitro assays, including CCK-8 proliferation, clonogenic survival, scratch wound healing, and Annexin V-FITC/PI apoptosis staining, and the results demonstrated that ERPP significantly inhibited HT-29 cell proliferation, suppressed colony formation, impaired migratory capacity, and induced apoptosis. JC-1 fluorescence assays provided further evidence of mitochondrial membrane potential (MMP) depolarization, as manifested by a substantial reduction in the red/green fluorescence ratio (from 10.87 to 0.35). These antitumor effects were further validated in vivo using a zebrafish HT-29 xenograft model. Furthermore, ERPP treatment significantly attenuated tumor angiogenesis and downregulated the expression of the vascular endothelial growth factor A (Vegfaa) gene in the zebrafish xenograft model. Mechanistic investigations revealed that ERPP primarily activated the mitochondrial apoptosis pathway. RT-qPCR analysis showed an upregulation of the pro-apoptotic gene Bax and a downregulation of the anti-apoptotic gene Bcl-2, leading to cytochrome c (CYCS) release and caspase-3 (CASP-3) activation. Additionally, ERPP exhibited potent antioxidant capacity, achieving an 80.2% hydroxyl radical scavenging rate at 4 mg/mL. ERPP also decreased reactive oxygen species (ROS) levels within the tumor cells, thereby augmenting anticancer efficacy through its antioxidant activity. Collectively, these findings provide mechanistic insights into the properties of ERPP, underscoring its potential as a functional food component or adjuvant therapy for colorectal cancer management.