Search Results (5,178)

Nanotechnology has emerged as a transformative tool in animal production, offering novel strategies to enhance productivity, health, and product quality. Among trace elements, selenium (Se) plays an essential role in antioxidant defence, immune regulation, and redox balance through its incorporation into selenoproteins. Selenium nanoparticles (SeNPs), synthesized via chemical, physical, or biological methods, have shown superior bioavailability, stability, and lower toxicity compared to traditional organic and inorganic selenium forms. This review explores the synthesis, physicochemical properties, and metabolic fate of SeNPs, emphasizing their advantages in poultry production systems. In poultry, SeNPs exhibit potent antioxidant and anti-stress effects by enhancing the activity of glutathione peroxidase, superoxide dismutase, and thioredoxin reductase, thereby mitigating lipid peroxidation and oxidative tissue damage. Their immunomodulatory effects are linked to improved lymphocyte proliferation, cytokine regulation, and increased immunoglobulin levels under normal and stress conditions. SeNP supplementation has been associated with enhanced growth performance, feed efficiency, carcass quality, and reproductive outcomes in broilers, layers, and quails. Furthermore, selenium nanoparticles have demonstrated therapeutic potential in preventing or alleviating chronic diseases such as cancer, diabetes, cardiovascular dysfunction, and neurodegenerative disorders. SeNPs also serve as biofortification agents, increasing selenium deposition in poultry meat and eggs, thus improving their nutritional value for human consumption. However, selenium’s narrow safety margin requires careful dose optimization to avoid potential toxicity. This review highlights the multifaceted benefits of selenium nanoparticles in poultry nutrition and health, while underscoring the need for further studies on grey SeNPs, long-term safety, and regulatory frameworks. Integrating SeNPs into poultry production represents a promising strategy to bridge animal health, food security, and public nutrition. Full article

Non-homologous end joining (NHEJ) is a critical DNA double-strand break (DSB) repair pathway that operates throughout the cell cycle to maintain the genomic stability of the cell. Unlike homologous recombination (HR), NHEJ is capable of repairing DSBs without the need for a homologous template, making it a rapid response mechanism, but potentially prone to errors. Central to NHEJ function and essential for the ligation through the recruitment and activation of additional repair factors, such as Artemis, XRCC4, and DNA ligase IV, is the DNA-dependent protein kinase (DNA-PK) complex. Dysregulation in the NHEJ pathway contributes to genomic instability, oncogenesis, and resistance to genotoxic therapies. Consequently, inhibitors of DNA-PK have emerged as promising therapeutic agents to sensitize tumor cells to radiation and DNA-damaging chemotherapeutics. Inhibiting the DNA-PK ability to recruit the protein complex needed for successful DSB repair promotes cell death through apoptosis or mitotic catastrophe. While inhibitors of DNA-PK can be used to enhance the effects of genotoxic therapies, the field still struggles to address critical problems: how to best exploit the differential DNA repair capacities among tumor subtypes, how to maximize radiosensitization of cancerous cells while sparing normal tissues, and how to translate preclinical studies into clinical benefits. Given that NHEJ constitutes the primary line of defense against radiation-induced damage, rapidly repairing the majority of double-strand breaks throughout the cell cycle, this review concentrates on targeting the DNA-PK complex, as the master regulator of this rapid-response mechanism, highlighting why its inhibition represents a strategic action to overcome intrinsic radioresistance. The implementation of DNA-PK inhibitors into medical practice can enable the stratification of oncologic patients into two categories, based on the tumors’ vulnerability to NHEJ disruptions. Thus, the therapeutic pathways of patients with NHEJ tumors could branch, combining traditional genotoxic therapies (radiation and DNA-damaging chemotherapeutics) with DNA-PK inhibitors to achieve an enhanced effect and improved survival outcomes. Full article

Modern medicine requires effective, continuous, and safe therapies, which largely depend on the targeted delivery and activity of the drug. This goal can be achieved by designing drug delivery systems with improved pharmacokinetic properties and enhanced drug transport to the affected tissue. Human serum albumin (HSA) is an attractive carrier for the synthesis of therapeutic nanoparticles, several of which have already been approved by the United States Food and Drug Administration (FDA). The success of Abraxane as an effective treatment for metastatic breast cancer and non-small cell lung carcinoma, the application of Optison in ultrasound imaging, and the use of Nanocoll as an agent for SPECT diagnostics in sentinel node localisation confirm the strong potential of albumin-based systems. Further benefits are expected in patients with soft tissue cancers, as LadRx is seeking FDA marketing approval for Aldoxorubicin. The future of oncology lies in theranostics, which combines a tumour-localising factor on one platform with a drug targeting cancer cells and a factor that activates the cytotoxicity of the drug after it reaches the target tissue. This article presents recent advancements in albumin-based nanoparticles for drug delivery, targeting, and imaging. It also briefly discusses methods of synthesis and surface modification of albumin nanocarriers to enable targeted delivery to pathological sites. Finally, it outlines the latest approaches in multimodal theranostic platforms, highlighting albumin’s potential to improve cancer therapy. Full article

Mesenchymal stromal cells (MSCs) are intensively investigated in oncology owing to their intrinsic tumor-homing ability and capacity to deliver therapeutic agents directly into the tumor microenvironment (TME). Recent advances in genetic engineering have enabled precise modification of MSCs, allowing controlled expression of therapeutic genes and other cargo delivery, thus improving targeting efficiency. As cellular carriers, MSCs have been engineered to transport oncolytic viruses, suicide genes in gene-directed enzyme prodrug therapy (GDEPT), multifunctional nanoparticles, and therapeutic factors such as IFN-β or TRAIL, while engineered MSC-derived extracellular vesicles (MSC-EVs) offer a promising cell-free alternative. These strategies increase intratumoral drug concentration, amplify bystander effects, and synergize with standard therapies while reducing systemic toxicity. Conversely, accumulating evidence highlights the tumor-promoting properties of MSCs: once recruited by inflammatory and hypoxic cues, they remodel the tumor microenvironment by stimulating angiogenesis, suppressing immune responses, differentiating into cancer-associated fibroblasts, and promoting epithelial-to-mesenchymal transition (EMT), ultimately enhancing invasion, metastasis, and therapy resistance. This duality has sparked both enthusiasm and concern in the oncology field. The present review outlines the paradoxical role of MSCs in oncology—ranging from their potential to promote tumor growth to their emerging utility as vehicles for targeted drug delivery. By highlighting both therapeutic opportunities and biological risks, we aim to provide a balanced perspective on how MSC-based strategies might be refined, optimized, and safely integrated into future cancer therapies. Full article

Cancer stem cells (CSCs) represent a small but highly resilient tumor subpopulation responsible for sustained growth, metastasis, therapeutic resistance, and recurrence. Their survival is supported by aberrant activation of developmental and inflammatory pathways, including Wnt/β-catenin, Notch, Hedgehog, PI3K/Akt/mTOR, STAT3, and NF-κB, as well as epithelial–mesenchymal transition (EMT) programs and niche-driven cues. Increasing evidence shows that phytochemicals, naturally occurring bioactive compounds from medicinal plants, can disrupt these networks through multi-targeted mechanisms. This review synthesizes current findings on prominent phytochemicals such as curcumin, sulforaphane, resveratrol, EGCG, genistein, quercetin, parthenolide, berberine, and withaferin A. Collectively, these compounds suppress CSC self-renewal, reduce sphere-forming capacity, diminish ALDH⁺ and CD44⁺/CD24⁻ fractions, reverse EMT features, and interfere with key transcriptional regulators that maintain stemness. Many phytochemicals also sensitize CSCs to chemotherapeutic agents by downregulating drug-efflux transporters (e.g., ABCB1, ABCG2) and lowering survival thresholds, resulting in enhanced apoptosis and reduced tumor-initiating potential. This review further highlights the translational challenges associated with poor solubility, rapid metabolism, and limited bioavailability of free phytochemicals. Emerging nanotechnology-based delivery systems, including polymeric nanoparticles, lipid carriers, hybrid nanocapsules, and ligand-targeted formulations, show promise in improving stability, tumor accumulation, and CSC-specific targeting. These nanoformulations consistently enhance intracellular uptake and amplify anti-CSC effects in preclinical models. Overall, the consolidated evidence supports phytochemicals as potent modulators of CSC biology and underscores the need for optimized delivery strategies and evidence-based combination regimens to achieve meaningful clinical benefit. Full article

Glioblastoma (GB) is one of the most aggressive and invasive cancers. Current treatment protocols for GB include surgical resection, radiotherapy, and chemotherapy with temozolomide. However, despite these treatments, physicians still struggle to effectively image, diagnose, and treat GB. As such, patients frequently experience recurrence of GB, demanding innovative strategies for early detection and effective therapy. Bioconjugated quantum dots (QDs) have emerged as powerful nanoplatforms for precision imaging and targeted drug delivery due to their unique optical properties, tunable size, and surface versatility. Due to their extremely small size, QDs can cross the blood–brain barrier and be used for precision imaging of GB. This review explores the integration of QDs with click chemistry for robust bioconjugation, focusing on artificial intelligence (AI) to advance GB therapy, mechanistic insights into cellular uptake and signaling, and strategies for mitigating toxicity. Click chemistry enables site-specific and stable conjugation of targeting ligands, peptides, and therapeutic agents to QDs, enhancing selectivity and functionalization. Algorithms driven by AI may facilitate predictive modeling, image reconstruction, and personalized treatment planning, optimizing QD design and therapeutic outcomes. We discuss molecular mechanisms underlying interactions of QDs with GB, including receptor-mediated endocytosis and intracellular trafficking, which influence biodistribution and therapeutic efficacy. Use of QDs in photodynamic therapy, which uses reactive oxygen species to induce apoptotic cell death in GB cells, is an innovative therapy that is covered in this review. Finally, this review addresses concerns associated with the toxicity of metal-based QDs and highlights how QDs can be coupled with AI to develop new methods for precision imaging for detecting and treating GB for induction of apoptosis. By converging nanotechnology and computational intelligence, bioconjugated QDs represent a transformative platform for paving a safer path to smarter and more effective clinical interventions of GB. Full article

Steroidal compounds lie at the crossroads of inflammation and cancer, where modulation of common signaling pathways creates opportunities for dual-action therapeutic intervention. Accumulating evidence indicates that their anti-inflammatory and antitumor activities are frequently interconnected, reflecting shared molecular mechanisms that regulate immune signaling, oxidative stress, cell proliferation, and apoptosis. This review provides a critical and comparative analysis of major classes of bioactive steroids—including furanosteroids, neo-steroids, aromatic steroids, α,β-epoxy steroids, peroxy steroids, cyanosteroids, nitro- and epithio steroids, halogenated steroids (fluorinated, chlorinated, brominated, iodinated), and steroid phosphate esters—with emphasis on their dual anti-inflammatory and anticancer potential. More than one thousand steroidal metabolites derived from plants, fungi, marine organisms, bacteria, and synthetic sources are surveyed. While the majority exhibit either anti-inflammatory or antineoplastic activity alone, only a limited subset displays potent activity in both domains. Comparative evaluation highlights the structural features that favor dual functionality, including epoxide, peroxide, nitrile, nitro, halogen, and phosphate ester moieties, as well as rearranged or heteroatom-enriched steroidal frameworks. Where available, biological data from in vitro and in vivo assays (IC₅₀ values, enzyme inhibition, cytokine modulation, and antiproliferative effects) are summarized and critically compared. Special attention is given to rare natural metabolites—such as polyhalogenated marine steroids, phosphorylated sterols, and heteroatom-containing derivatives—as well as synthetic analogues designed to enhance cytotoxic or immunomodulatory efficacy. Mechanistically, steroids exhibiting dual activity commonly modulate convergent signaling pathways, including NF-κB, JAK/STAT, MAPK, PI3K/AKT, redox homeostasis, and apoptosis regulation. Collectively, these findings underscore the potential of structurally optimized steroids as multifunctional therapeutic agents and provide a framework for the rational design of next-generation anti-inflammatory and anticancer drugs. Full article

Melanoma is an aggressive skin cancer that continues to present major therapeutic difficulties. Although targeted drugs and immune checkpoint inhibitors have improved outcomes, resistance and treatment-related toxicity limit long-term benefit. In recent years, nanotechnology has been explored as a way to improve how drugs are delivered and to achieve greater tumor selectivity. Among available nanocarriers, liposomes have attracted particular interest. Built from lipid bilayers, they can carry both hydrophilic and hydrophobic molecules, and they are generally well tolerated. Importantly, their surface can be modified with polymers or targeting ligands to direct the carrier more selectively to melanoma cells. Experimental models show that liposomal drug formulations can increase concentrations in tumor tissue while limiting distribution to healthy organs. They have also been used successfully to combine different types of agents, chemotherapies, immunomodulators, and nucleic acids, within a single delivery system. These findings suggest genuine potential to address several of the shortcomings of conventional treatments. Although translation to the clinic is slowed by challenges such as formulation stability and large-scale production, liposomes represent an important step toward safer and more effective melanoma therapy within the broader field of oncologic nanotechnology. Full article

The arachidonic acid pathway plays a pivotal role in the biosynthesis of important inflammatory and signal transducing agents such as prostaglandins, leukotrienes and thromboxanes. When this pathway is deregulated, it leads to pathological conditions such as cardiovascular diseases, metabolic diseases, and cancer. Two key enzymes of the pathway are cyclooxygenases (COXs) and lipoxygenases (LOXs), which are responsible for the production of prostaglandins and leukotrienes, respectively. Consequently, these enzymes have long been recognized as key therapeutic targets for the treatment and management of inflammatory disorders and other pathological conditions associated with inflammation. In this review, we describe the new evidence over the last 4 years regarding the arachidonic acid pathway. Moreover, we will pay attention to the structure and function of the COX-2 and 5-LOX enzymes and their role in inflammation, as well as define their active sites. Later, we will discuss the most potent, dual inhibitors of COX-2 and 5-LOX enzymes, based on in vitro and in vivo experiments, from 2020–2024. Structure–activity relationship (SAR) analysis of these compounds revealed four key structural features required for potent dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX). We refer to these criteria as “The Rule of Four for Inflammation”. Full article

Background and Objectives: Aggressive cancer development is characterized by rapid tumor growth and progressive immune dysfunction. Tumor-derived microRNAs (miRNAs) emerge as master regulators of both malignant transformation and immune evasion, making them promising therapeutic targets. Using the highly aggressive CT-26 peritoneal adenomatosis model, this study explored the potential of selective miRNA inhibition to simultaneously suppress tumor growth and overcome immunosuppression. Methods and Results: Our results revealed that inhibition of miR-155, miR-21, and miR-17 by methylsulfonyl phosphoramidate (mesyl) oligonucleotides exhibited markedly different therapeutic profiles. miR-155 inhibition demonstrated minimal efficacy. miR-21 suppression provided early tumor regression and prevented cancer-associated thymic atrophy, translating into extended survival. miR-17 inhibition displayed delayed but superior tumor growth inhibition, significantly reducing pathologically elevated polymorphonuclear myeloid-derived suppressor cell (MDSC) populations, and nearly doubled animal lifespan. Combination therapy targeting all three miRNAs integrated these complementary mechanisms, maintaining consistent anti-tumor efficacy across early and late stages while providing thymic protection and MDSC reduction. Importantly, therapeutic responses in vivo substantially exceeded predictions based on in vitro tumor cell proliferation and motility measurements, revealing critical contributions of systemic immunomodulation. Conclusions: These findings demonstrate that miRNA inhibition reshapes tumor–immune interactions, positioning anti-miRNA therapeutics as immunomodulatory agents for effective colorectal cancer treatment. Full article

Liver cancer, also known as hepatocellular carcinoma (HCC), remains a major global health concern, with high mortality driven by late-stage diagnosis, limited treatment efficacy, and frequent therapeutic resistance. Matrix metalloproteinases (MMPs), a large family of zinc-dependent endopeptidases, are central to the biological processes that drive liver tumor initiation and progression. By degrading and reorganizing extracellular matrix components, MMPs facilitate tumor expansion, tissue invasion, and metastatic dissemination. In addition, these enzymes regulate the availability of growth factors, cytokines, and chemokines, thereby influencing angiogenesis, inflammation, immune cell recruitment, and the development of an immunosuppressive tumor microenvironment. Aberrant expression or activity of multiple MMP family members is consistently associated with aggressive clinicopathologic features, including vascular invasion, increased metastatic potential, and reduced patient survival, highlighting their promise as prognostic markers and actionable therapeutic targets. Past attempts to modulate MMP activity were hindered by broad inhibition profiles and dose-limiting toxicities, underscoring the need for improved specificity and delivery strategies. Recent advances in molecular design, biologics engineering, and nanotechnology have revitalized interest in MMP targeting by enabling more selective, context-dependent modulation of proteolytic activity. Preclinical studies demonstrate that carefully tuned MMP inhibition can limit tumor invasion, enhance anti-angiogenic responses, and potentially improve the efficacy of existing systemic therapies, including immuno-oncology agents. This review synthesizes current knowledge on the multifaceted roles of MMPs in HCC pathobiology and evaluates emerging therapeutic strategies that may finally unlock the clinical potential of targeting these proteases. Full article

The progression of neoplastic diseases is driven by a complex interplay of biological processes, including uncontrolled proliferation, enhanced invasion, metastasis, and profound metabolic reprogramming. Among the hallmarks of cancer, as revised by Hanahan and Weinberg, the reprogramming of energy metabolism has emerged as a critical feature that enables cancer cells to meet their heightened bioenergetic and biosynthetic demands. One significant aspect of this metabolic adaptation is the accumulation of lipid droplets (LDs) dynamic, cytoplasmic organelles primarily involved in lipid storage and metabolic regulation. LDs serve as reservoirs of neutral lipids and play a multifaceted role in cancer cell physiology. Their accumulation is increasingly recognized as a marker of tumor aggressiveness and poor prognosis. By storing lipids, LDs provide a readily accessible source of energy and essential building blocks for membrane synthesis, supporting rapid cell division and growth. Moreover, LDs contribute to cellular homeostasis by modulating oxidative stress, maintaining redox balance, and regulating autophagy, particularly under nutrient-deprived or hypoxic conditions commonly found in the tumor microenvironment. Importantly, LDs have been implicated in the development of resistance to cancer therapies. They protect cancer cells from the cytotoxic effects of chemotherapeutic agents by buffering endoplasmic reticulum (ER) stress, inhibiting apoptosis, and facilitating survival pathways. The presence of LDs has been shown to correlate with increased resistance to a variety of chemotherapeutic drugs, although the precise molecular mechanisms underlying this phenomenon remain incompletely understood. Emerging evidence suggests that chemotherapy itself can induce changes in LD accumulation, further complicating treatment outcomes. Given their central role in cancer metabolism and therapy resistance, LDs represent a promising target for therapeutic intervention. Strategies aimed at disrupting lipid metabolism or inhibiting LD biogenesis have shown potential in sensitizing cancer cells to chemotherapy and overcoming drug resistance. In this review, we comprehensively examine the current understanding of LD biology in cancer, highlight studies that elucidate the link between LDs and drug resistance, and discuss emerging approaches to target lipid metabolic pathways to enhance therapeutic efficacy across diverse cancer types. Full article

Background/Objectives: To improve the response rate of immune checkpoint inhibitors (ICIs), inducing immunogenic cell death (ICD) is a promising approach. Photothermal therapy (PTT) induces immunogenic cell death and activates anti-tumor immunity. While there are various ICD inducers, the difference in ICD induction by various modalities is poorly understood. In this study, we found previously unrecognized advantages of PTT compared to anti-cancer drugs and showed the usefulness of PTT as an anti-cancer drug-free approach to be combined with immunotherapy. Methods: Gold nanorods were synthesized as photothermal agents and added to culture medium or locally administered to tumor tissues. Mitoxantrone (MIT), an ICD inducer, and cisplatin (CDDP), a non-ICD inducer, were compared with PTT. To assess the induction of ICD, the subcellular localization and amounts of high mobility group box 1 (HMGB1) and calreticulin (CRT) were observed using immunofluorescent staining. FM3A tumor-bearing mice were treated with PTT or anti-cancer drugs, and cell death and DAMPs localization in tumor tissues were analyzed. Also, the supra-additive effect of PTT on ICI was observed. Tumor-infiltrating CD8⁺ T cells were examined to evaluate the immune status in tumor tissues. Results: In vivo assays showed that PTT induces HMGB1 release and increased expression of CRT on the cell membrane. Moreover, PTT showed a supra-additive effect in terms of therapeutic effect and anti-tumor activation when combined with an immune checkpoint inhibitor. Conclusions: In this study, we demonstrated that PTT induced ICD-related signaling and improved the response rate of ICI, which means PTT is a promising combination therapy with ICI. Full article

Background/Objectives: Mesenchymal stem cells (MSCs) are deemed to be a highly safe model for autologous and allogeneic cellular therapy, owing to their inherent lack of HLA-DR expression, immunomodulatory properties, homing ability, and plasticity allowing differentiation into different cell types. The interest in activating autophagic signaling in MSCs has recently grown due to its significant potential in maintaining stemness, enhancing paracrine signaling, and providing therapeutic benefits for cancer and neurodegenerative diseases. This study aimed to explore the impact of autophagy induction on enhancing the therapeutic potential of MSCs by maintaining their plasticity and to assess different induction agents. Methods: In this study, MSCs were first extracted from the fat tissue of Sprague–Dawley (SD) rats and characterized phenotypically and molecularly by their positive expression of stemness markers CD29, CD106, and CD44, and their negative expression of hematopoietic surface markers CD14, CD34, and CD45, using a flow cytometry approach. Isolated MSCs were then treated separately with two FDA-approved autophagy inducers: Lithium Chloride and Trehalose, following assessment of autophagy activity. Results: Treated MSCs showed significant increases in autophagic activity at both the transcriptional and translational levels. The successful induction of autophagy in MSCs was confirmed through the elevated expression of autophagy-related genes such as ATG3, ATG13, ATG14, P62, and ULK1. These data were confirmed by the significant upregulation in LC3 protein expression and the formation of autophagosomes, which was detected using a transmission electron microscope. Furthermore, the expression of Oct4, Sox2, and Nanog genes was significantly enhanced after treatment with Trehalose and Lithium Chloride compared with untreated control MSCs which may indicate an upregulation of pluripotency. Meanwhile, Lithium Chloride and Trehalose did not significantly induce cellular apoptosis, indicated by the Bax/Bcl-2 expression ratio, and significantly decreased the expression of the antioxidant markers SOD and GPx. Conclusions: Treatment of MSCs with Trehalose and, in particular, Lithium Chloride significantly activated autophagic signaling, which showed a profound effect in enhancing cells’ pluripotency, reinforcing the usage of treated MSCs for autologous and/or allogenic cellular therapy. However, further in vivo studies for activating autophagy in cellular grafts should be conducted before their use in clinical trials. Full article

Background: Vitamin E has been studied for its role in reducing the growth of colorectal cancer (CRC). CRC is a worldwide health concern. A meta-analysis reported that CRC patients have a lower concentration of serum vitamin E, suggesting it to be a risk factor. Although rodent models are widely used in disease research, their application in studying vitamin E as a preventive or therapeutic agent in CRC is not well characterized. To address this gap, we conducted a scoping review to examine the available evidence, adhering to the PRISMA-ScR checklist. Methods: We searched PubMed, Google Scholar, Scopus, and Web of Science (WoS) for full-text English original articles published before May 2024, using Medical Subject Headings (MeSH) terms and free text. The following search string strategy was applied: (Vitamin E OR tocopherol$ OR tocotrienol$) AND (Colo$ cancer OR colo$ carcinoma) AND (Rodentia OR mouse OR Rodent$ OR mice OR murine OR rats OR guinea OR rabbit OR hamsters OR Animal model OR Animal testing OR animals) AND (neoplasm$ OR “tumor mass” OR tumor volume OR tumor weight OR tumor burden). Data were charted into five categories using a standardized, pretested form. The charted data were synthesized using descriptive and narrative methods. Conclusions: This study highlights that γ- and δ-tocopherols, as well as δ-tocotrienol and its metabolites, were reported to reduce tumor volume and formation in various rodent models. While these results are promising, this scoping review identifies a need for further research to address translational barriers such as dosing, bioavailability, and long-term safety before clinical application. Full article