Search Results (542)

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. Full article

Deoxynojirimycin (DNJ), the first isolated iminosugar, is a natural alkaloid acting as a potent inhibitor of α-glucosidase with high nutritional value. It naturally occurs in plants (especially Morus spp.), microbes, and insects or can be synthesized. Diverse biological activities, such as antihyperglycemic, lipid-lowering, antitumor, antiviral, and anti-inflammatory, have been recognized for this compound. However, DNJ has not been approved as a food supplement until now. Several studies, also in clinics, are carried out on Morus spp. containing DNJ. Among Morus spp., Morus alba L. (white mulberry), Morus nigra L. (black mulberry), and Morus rubra L. (red mulberry) are the three main species that grow all over the world. Some spurious studies have been conducted on Reducose^® and Glubloc™, two products that contain DNJ and Morus alba, respectively. However, mulberry allergy, including respiratory allergy, airborne contact urticaria, anaphylaxis, oral allergy syndrome, and food induced urticaria, may be observed. This review aims to explore a crucial and timely question: how DNJ exerts its biological effects and what role it may play in therapeutic applications. We provide a comprehensive summary of the current understanding of DNJ’s pharmacological potential and the methods used for its production. We also report recent developments in clinical studies on Morus alba, Reducose^® and Glubloc™. Full article

In recent decades, there has been a marked surge in the development of marine-by-product-derived ingredients for cosmetic applications, driven by the increasing demand for natural, sustainable, and high-performance formulations. Marine animal by-products, particularly those from fish, crustaceans, and mollusks, represent an abundant yet underutilized source of bioactive compounds with notable potential in cosmeceutical innovation. Generated as waste from the fishery and seafood-processing industries, these materials are rich in valuable bioactives, such as chitosan, collagen, peptides, amino acids, fatty acids, polar lipids, lipid-soluble vitamins, carotenoids, pigments, phenolics, and mineral-based substrates like hydroxyapatite. Marine by-product bioactives can be isolated via several extraction methods, and most importantly, green ones. These compounds exhibit a broad spectrum of skin-health-promoting effects, including antioxidant, anti-aging, anti-inflammatory, antitumor, anti-wrinkle, anti-hyperpigmentation, and wound-healing properties. Moreover, applications extend beyond skincare to include hair, nail, and oral care. The present review provides a comprehensive analysis of bioactives obtained from marine mollusks, crustaceans, and fish by-products, emphasizing modern extraction technologies with a focus on green and sustainable approaches. It further explores their mechanisms of action and documented efficacy in cosmetic formulations. Finally, the review outlines current limitations and offers future perspectives for the industrial valorization of marine by-products in functional and environmentally-conscious cosmetic development. Full article

The marine seaweed Undaria pinnatifida belongs to the large group of brown macroalgae (Ochrophyta) and is valued both as a nutritious food and a source of pharmaceutical compounds. It has been widely consumed in East Asia as part of the traditional diet and is generally regarded as a “healthy longevity food.” Consequently, it represents one of the most promising natural sources of biomedicinal and bioactive products. This review aims to synthesize current scientific evidence on the pharmacologically active compounds of U. pinnatifida, emphasizing their mechanisms of action and therapeutic potential in neurodegenerative and chronic diseases. This narrative review is based on a comprehensive literature search of peer-reviewed articles from scientific databases, focusing on studies addressing the pharmacological properties of U. pinnatifida and its major bioactive constituents. Recent research highlights that compounds such as fucoxanthin (a carotenoid), fucosterol (a sterol), fucoidan (a polysaccharide), alginate, and dietary fiber found in U. pinnatifida possess significant potential for developing treatments for conditions including goitre, urinary diseases, scrofula, dropsy, stomach ailments, and hemorrhoids. Moreover, these compounds exhibit remarkable pharmacological properties, including immunomodulation, antitumor, antiviral, antioxidant, antidiabetic, anti-inflammatory, anticoagulant, antithrombotic, and antibacterial activities, all with low toxicity and minimal side effects. Additionally, U. pinnatifida shows promise in the treatment or prevention of neurodegenerative diseases such as Alzheimer’s and Parkinson’s, as well as neuropsychiatric conditions like depression, supported by its antioxidant effects against oxidative stress and neuroprotective activities. Numerous in vitro and in vivo studies have confirmed that U. pinnatifida polysaccharides (UPPs), particularly fucoidans, exhibit significant biological activities. Thus, accumulating evidence positions UPPs as promising therapeutic agents for a variety of diseases. Full article

Peptides play a crucial role in the development of pharmaceuticals and functional foods. Multiple studies have shown that natural bioactive peptides possess antioxidant, antihypertensive, anti-tumor, and anti-inflammatory activities. Marine bioactive peptides, especially those sourced from fish, constitute a substantial reservoir of these molecules. Although considerable research has been undertaken on fish-derived peptides, studies specifically concerning those from tuna are limited. Tuna, a marine fish of high nutritional value, generates substantial by-product waste during fishing and processing. Therefore, it is essential to conduct an evaluation of the advancements in study on tuna-derived active peptides and to offer a perspective on the direction of future investigations. This review integrates prospective bioactive peptides derived from tuna and reports contemporary strategies for their investigation, including extraction, purification, screening, identification, and activity evaluation procedures, including Yeast Surface Display (YSD) and molecular docking. This review seeks to promote the continued investigation and application of bioactive peptides derived from tuna. Full article

Introduction: Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. Even though surgery and chemotherapy are the mainstay of treatment, immunotherapy, and more specifically anti-tumor vaccination, has gained popularity over the past years due to the lower related toxicity and fewer long-term side effects. Dendritic cell (DC) vaccines have been shown to induce tumor specific cytotoxic T-cell (CTL) responses both in vitro and in vivo; however, due to the nature of the disease, resistance to immunotherapy is often developed. Various modifications, such as the implementation of viral vectors, tumor RNA, or even tumor-specific peptides (neoantigens), have been studied as a means to avoid resistance and enhance the effectiveness of the vaccines. In this review, we aim to assess the effects of neoantigen-loaded DC vaccines (naDCVs) on the immune response against gastric cancer cells. Materials and methods: A thorough literature search was conducted on PubMed and clinicaltrials.gov for studies assessing the efficacy of naDCVs against gastric cancer both in vivo and in vitro. The studies were assessed for eligibility by two independent reviewers based on predetermined inclusion and exclusion criteria. The search was completed following the PRISMA guidelines. Results: Eleven studies were included in our systematic review. In five of the studies, the effects of the naDCVs were tested in vitro; in two and in four they were examined both in vitro and in vivo. The in vitro studies showed that the naDCVs resulted in a more robust immune response against the cancer cells in the study groups compared to the control groups. The in vivo studies conducted on mice showed that tumor volume was reduced in the groups treated with the naDCV compared to the untreated groups. What is more, the cytotoxic effect of CTLs against tumor cells was also increased in the vaccine groups. One of the studies was conducted on humans as a phase I study. The results show increased CTL proliferation and cytokine production in the vaccinated group compared to the control, but no difference regarding the tumor size was observed. Conclusions: Neoantigen-loaded DC vaccines can stimulate a strong immune response against specific gastric cancer cell peptides and enhance tumor cell lysis, therefore hindering or even reversing disease progression, offering great potential for the treatment of patients with gastric cancer. Full article

Chimeric antigen receptor (CAR)-engineered natural killer (NK) cells are a promising platform for off-the-shelf immunotherapy due to their safety advantages over CAR-T cells, including lower risk of graft-versus-host disease, cytokine release syndrome, and neurotoxicity. However, their persistence and efficacy are limited by immunological challenges such as host T-cell-mediated rejection, NK cell fratricide, and macrophage-mediated clearance. This review summarizes gene editing strategies to overcome these barriers, including β2-microglobulin (B2M) knockout and HLA-E overexpression to evade T and NK cell attacks, CD47 overexpression to inhibit phagocytosis, and TIGIT deletion to enhance cytotoxicity. In addition, we discuss functional enhancements such as IL-15 pathway activation, KIR modulation, and transcriptional reprogramming (e.g., FOXO1 knockout) to improve persistence and antitumor activity. We also highlight the role of induced pluripotent stem cell (iPSC)-derived NK platforms, enabling standardized, scalable, and multiplex gene-edited products. Finally, we explore artificial intelligence (AI) applications in immunogenomic profiling and predictive editing to tailor NK cell therapies to patient-specific HLA/KIR/SIRPα contexts. By integrating immune evasion, functional reinforcement, and computational design, we propose a unified roadmap for next-generation CAR-NK development, supporting durable and broadly applicable cell-based therapies. Full article

Chimeric antigen receptor (CAR)-engineered immune cells, particularly CAR T lymphocytes and CAR natural killer (NK) cells, have revolutionized cancer immunotherapy. However, their therapeutic efficacy and safety can be influenced by the tumor microenvironment, particularly the presence of mesenchymal stem cells (MSCs). MSCs are immunomodulatory cells which can alter the function of tumor-infiltrated immune cells in both supportive and suppressive ways. Results obtained in recently conducted experimental studies demonstrate that MSCs modulate proliferation, cytotoxicity, cytokine production and anti-tumor activity in CAR-expressing immune cells in both a juxtacrine and a paracrine manner. While MSCs can enhance CAR cell viability and persistence through trophic support, they may also impair cytotoxic function and promote an immunosuppressive phenotype under certain conditions. Understanding the dualistic nature of MSCs in CAR-based immunotherapy for malignant diseases is critical for optimizing clinical outcomes. Additionally, MSCs may serve as vehicles for targeted delivery of immunomodulatory agents, and should be considered as active components in the design of next-generation CAR-based immunotherapies. Accordingly, in this review article we emphasize molecular and cellular mechanisms involved in MSC-dependent modulation of CAR-expressing immune cells, paving the way for more efficient CAR-based immunotherapy for malignant diseases. Full article

This article reviews the mechanisms by which marine natural products regulate ferroptosis and their potential applications in tumor therapy. Ferroptosis is a form of programmed cell death driven by iron-dependent lipid peroxidation, characterized primarily by the accumulation of lipid peroxides and the failure of antioxidant defense systems. Due to their unique chemical structural diversity, marine natural products demonstrate significant advantages in regulating the ferroptosis pathway. Studies showed that marine compounds target key molecules such as glutathione peroxidase 4 (GPX4) and long-chain acyl-CoA synthetase 4 (ACSL4(a)) ACSL4(1) to modulate lipid peroxidation and iron metabolism, inducing ferroptosis in tumor cells and reshaping the tumor microenvironment (TME). In addition, marine compounds can enhance anti-tumor effects by activating immune responses. Although marine compounds hold great potential in regulating ferroptosis, their clinical translation faces challenges such as low bioavailability and tumor type dependency. Future research needs to integrate multi-omics techniques to further analyze the mechanisms of marine compounds and develop precision therapeutic strategies based on marine compounds to overcome the bottlenecks in ferroptosis therapy. Full article

Cancer treatment remains a formidable challenge globally. Natural products, particularly natural alkaloids, have emerged as significant resources for the development of novel anti-tumor drugs due to their structural diversity and unique biological activities. Our team previously isolated an alkaloid, 6-hydroxymethyldihydrochelerythrine (6-HMDN), from Zanthoxylum ailanthoides. Subsequent in vitro and in vivo activity screenings, utilizing cell-based assays and a zebrafish xenograft model, revealed that 6-HMDN significantly inhibited the proliferation of HepG2 and MCF7 cells and effectively suppressed HepG2 cell migration. Mechanistic studies indicated that 6-HMDN induced tumor cell apoptosis by modulating the Bcl-2/Bax protein balance and activating the caspase cascade. Furthermore, 6-HMDN augmented intracellular reactive oxygen species (ROS) levels, thereby promoting ferroptosis, as evidenced by lipid ROS accumulation and glutathione (GSH) depletion. Additionally, 6-HMDN attenuated focal adhesion kinase (FAK) phosphorylation, leading to the inhibition of tumor cell migration. In vivo experiments further substantiated the capacity of 6-HMDN to effectively suppress tumor proliferation and metastasis. These findings demonstrate that 6-HMDN exhibits potent anti-tumor activity, exerting its effects through multiple mechanisms involving the regulation of apoptosis, ferroptosis, and the FAK signaling pathway. Therefore, 6-HMDN may be considered a promising candidate for anti-tumor drug development. Full article

Background/Objectives: Camellia nitidissima Chi (C. nitidissima), a traditional Chinese “food and medicine homology” plant, has demonstrated potential anti-tumor properties. However, its mechanisms of anti-lung cancer activity via ferroptosis remain unclear. This study aimed to construct an integrated research system of “natural product extraction-purification, bioactivity evaluation, and computational drug screening” to explore the bioactive compounds in C. nitidissima leaves targeting HMOX-1-mediated ferroptosis and their anti-lung cancer mechanisms. Methods: Active fractions were prepared using ethanol extraction combined with polyamide column chromatography. The anti-lung cancer activity was evaluated using the NCI-H1975 cell model. Ferroptosis was verified via transmission electron microscopy (TEM), biochemical indicators, a PCR Array, and immunofluorescence. The bioactive compounds were identified using UPLC-Q Exactive MS, and their binding affinity to HMOX-1 was evaluated via molecular docking and dynamics simulations, followed by cellular validation. Results: The 95% F1 fraction from the extracts of C. nitidissima leaves exhibited the strongest anti-lung cancer activity, which could be significantly reversed by Ferrostatin-1. Furthermore, it induced typical ferroptosis-related structural damage in mitochondria, including shrinkage and a reduction in size, increased membrane density, and a reduction or even the disappearance of cristae structures. At the molecular level, this fraction significantly increased the levels of oxidative stress markers (ROS↑, MDA↑, Fe²⁺↑, and GSH↓) and upregulated the expression of key ferroptosis-related genes, including HMOX-1, CHAC1, and NOX1. Using UPLC-Q Exactive MS combined with computational simulation methods, four bioactive compounds with high affinity for HMOX1 were successfully identified, including isochlorogenic acid A (−8.4 kcal/mol), isochlorogenic acid C (−8.4 kcal/mol), apigenin (−7.8 kcal/mol), and chrysin (−7.3 kcal/mol). Cellular experiments validated that these compounds exhibited dose-dependent anti-proliferative effects. Conclusions: The leaves of C. nitidissima induce anti-lung cancer effects via HMOX-1-mediated ferroptosis. Isochlorogenic acid A/C, apigenin, and chrysin were identified as key bioactive components. These findings lay the foundation for the development of natural ferroptosis-targeted drugs. Full article

Orphan nuclear receptor 4A1 (NR4A1, Nur77) plays a crucial role in regulating immune cell metabolism and function within the tumor microenvironment (TME), thus influencing cancer progression and serving as a potential therapeutic target for cancer immunotherapy. A comprehensive review discussing the multifaceted roles of NR4A1 in immune cells and the exploitation of that knowledge for therapeutic development is lacking in the field. This review explores diverse functions of NR4A1 in tumor-associated immune cells, including T cells, monocytes, natural killer cells, B cells, dendritic cells, macrophages, and neutrophils. NR4A1 contributes to immune regulation by impacting cytokine production, cell differentiation, and immune cell exhaustion. We highlight how NR4A1 in immune cells within the TME may be either a positive (e.g., macrophages in colon cancer) or negative prognostic factor (e.g., T cells in melanoma), depending on the cancer and immune cell context. Additionally, this review also highlights potential therapeutic strategies targeting NR4A1, leading to its inhibition, activation, or degradation to restore immune cell function and enhance anti-tumor immunity. Such therapies could potentially improve patient outcomes by altering immune cell behaviors, blocking intrinsic tumor growth pathways, or via both mechanisms. However, the development of NR4A1-targeted therapies will be dependent on further research to better understand lineage-specific roles of NR4A1 and the underlying mechanisms across different cancer types and immune cells. Full article

Galaxamide, an N-methylated cyclo-pentapeptide containing five D-leucines isolated from Galaxaura filamentosa, has shown significant antitumor activity. This unique cyclo-pentapeptide offered a fresh skeleton for structural modifications. Herein, galaxamide and its 23 analogs (Gala01~Gala24) were designed and synthesized by substituting D-leucine with various proteinogenic amino acids or altering the amino acid configuration using the “3 + 2” strategy, and the in vitro antitumor activity of these cyclopeptides was studied utilizing the CCK-8 assay against two human tumor cell lines (A549 and K562) and one human normal cell line (293T). The total yields of galaxamide and its analogs reached 9.7% and 9.1–16.0%, respectively. CCK-8 assays demonstrated that these compounds showed broad-spectrum antitumor activity, with Gala04 exhibiting outstanding activity against K562 cells (IC₅₀ = 4.2 µM). The anticancer efficacy of galaxamide analogs against tumor cell lines was significantly influenced by the quantity of D-leucines and the D-leucine position. Full article

CD300 family members are immunoglobulin superfamily receptors that regulate immune cell function through either activating or inhibitory signals. Among them, CD300a is a prototypical inhibitory receptor, highly expressed in both myeloid and lymphoid lineages, and plays a pivotal role in the pathogenesis of inflammation and tumor immunity. CD300a transduces inhibitory signals in several immune cells—including mast cells, eosinophils, monocytes, dendritic cells (DCs), neutrophils, and natural killer (NK) cells—by recruiting SHP-1 phosphatase to immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and suppressing activation pathways such as Toll-like receptor (TLR)-MyD88 and FcεRI signaling. Recent studies suggest that tumor cells may hijack CD300a-associated pathways to establish an immunosuppressive microenvironment that facilitates immune evasion, tumor survival, and potentially metastatic spread. Proposed mechanisms include reduced DC-mediated type I interferon (IFN) production, diminished NK cell cytotoxicity, and negative regulation of mast cell– and eosinophil-dependent anti-tumor responses. Although some of these findings are derived from in vivo models, the cumulative evidence positions CD300a as a critical immune checkpoint in tumor-associated immune regulation. In addition to its established roles in hematologic malignancies—including chronic lymphocytic leukemia, acute lymphoblastic leukemia, and acute myeloid leukemia—CD300a has also been implicated in modulating tumor-associated immune responses in other pathological contexts. While most studies emphasize its immune cell–mediated effects, emerging evidence suggests that CD300a may directly influence tumor progression by regulating immune homeostasis, intracellular signaling, and tumor microenvironment interactions. Collectively, these findings establish CD300a as a pleiotropic immunoregulatory molecule in both hematologic and non-hematologic malignancies, underscoring the need to further explore its broader relevance and therapeutic potential in cancer immunology. Full article

Unconventional T (UC T) cells, including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells, γδ T cells, and double-negative (DN) T cells, are key players in immune surveillance and response due to their properties combining innate-like and adaptive-like features. These cells are widely present in mucosal tissues, where they can rapidly respond to infections and tumor-associated changes. In fact, UC T cells can have both pro- and anti-tumoral effects, with their activity influenced by factors such as microbial composition and the tumor microenvironment. In particular, intratumoral microbiota significantly impacts the development, function, and activation of UC T cells, influencing cytokine production and shaping the immune response in various cancers. The complex crosstalk between UC T cells and the surrounding factors is discussed in this review, with a focus on how these cells might be interesting candidates to explore and exploit as anticancer therapeutic agents. However, the great potential of UC T cells, not only demonstrated in the context of adoptive cell transfer, but also enhanced through techniques of engineering, is still flanked by different challenges, like the immunosuppressive tumor microenvironment and heterogeneity of target molecules associated with some specific categories of tumors, like gastrointestinal cancers. Full article