Search Results (676)

Background/Objectives: Curcumin (CUR) is well known for its therapeutic properties, particularly attributed to its antioxidant and anti-inflammatory effects in managing chronic diseases such as arthritis. While CUR application for biomedical purposes is well known, the phytochemical has several restrictions given its poor water solubility, physicochemical instability, and low bioavailability. These limitations have led to innovative formulations, with nanocarriers emerging as a promising alternative. For this reason, this study aimed to address the potential advantages of associating CUR with nanocarrier systems in managing arthritis through a scoping review. Methods: A systematic literature search of preclinical (in vivo) and clinical studies was performed in PubMed, Scopus, and Web of Science (December 2024). General inclusion criteria include using CUR or natural derivatives in nano-based formulations for arthritis treatment. These elements lead to the question: “What is the impact of the association of CUR or derivatives in nanocarriers in treating arthritis?”. Results: From an initial 536 articles, 34 were selected for further analysis (31 preclinical investigations and three randomized clinical trials). Most studies used pure CUR (25/34), associated with organic (30/34) nanocarrier systems. Remarkably, nanoparticles (16/34) and nanoemulsions (5/34) were emphasized. The formulations were primarily presented in liquid form (23/34) and were generally administered to animal models through intra-articular injection (11/31). Complete Freund’s Adjuvant (CFA) was the most frequently utilized among the various models to induce arthritis-like joint damage. The findings indicate that associating CUR or its derivatives with nanocarrier systems enhances its pharmacological efficacy through controlled release and enhanced solubility, bioavailability, and stability. Moreover, the encapsulation of CUR showed better results in most cases than in its free form. Nonetheless, most studies were restricted to the preclinical model, not providing direct evidence in humans. Additionally, inadequate information and clarity presented considerable challenges for preclinical evidence, which was confirmed by SYRCLE’s bias detection tools. Conclusions: Hence, this scoping review highlights the anti-arthritic effects of CUR nanocarriers as a promising alternative for improved treatment. Full article

Recently, a number of natural biologically active substances have been proven to be attractive alternatives to conventional anticancer medicine or as adjuvants in contemporary combination therapies. Although lignin-based materials were previously accepted as waste materials with limited usefulness, recent studies increasingly report the possibility of their use for novel applications in various industrial branches, including biomedicine. In this regard, the safety, efficiency, advantages and limitations of lignin compounds for in vitro/in vivo applications remain poorly studied and described. This study was carried out to investigate the possibility of using newly synthesized, alkali lignin-based micro-/nano-biopolymer formulations (Lignin@Formulations/L@F) as carriers for substances with antioxidant and/or anticancer effectiveness. Moreover, we tried to assess the opportunity for using an electro-assisted approach for achieving improved intracellular internalization. An investigation was conducted on an in vitro panel of breast cell lines, namely two breast cancer lines with different metastatic potentials and one non-tumorigenic line as a control. The characterization of all tested formulations was performed via DLS (dynamic light scattering) analysis. We developed an improved separation procedure via size/charge unification for all types of Lignin@Formulations. Moreover, in vitro applications were investigated. The results demonstrate that compared to healthy breast cells, both tested cancer lines exhibited slight sensitivity after treatment with different formulations (empty or loaded with antioxidant substances). This effect was also enhanced after applying electric pulses. L@F loaded with Quercetin was also explored only on the highly metastatic cancer cell line as a model for the breast cancer type most aggressive and non-responsive to traditional treatments. All obtained data suggest that the tested formulations have potential as carriers for the electro-assisted delivery of natural antioxidants such as Quercetin. Full article

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. Full article

The protein p53, often referred to as the “guardian of the genome,” is essential for preserving cellular balance and preventing cancerous transformations. As one of the most commonly altered genes in human cancers, its impaired function is associated with tumor initiation, development, and resistance to treatment. Exploring the diverse roles of p53, which include regulating the cell cycle, repairing DNA, inducing apoptosis, reprogramming metabolism, and modulating immunity, provides valuable insights into cancer mechanisms and potential treatments. This review integrates recent findings on p53′s dual nature, functioning as both a tumor suppressor and an oncogenic promoter, depending on the context. Wild-type p53 suppresses tumors by inducing cell cycle arrest or apoptosis in response to genotoxic stress, while mutated variants often lose these functions or gain novel pro-oncogenic activities. Emerging evidence highlights p53′s involvement in non-canonical pathways, such as regulating tumor microenvironment interactions, metabolic flexibility, and immune evasion mechanisms. For instance, p53 modulates immune checkpoint expression and influences the efficacy of immunotherapies, including PD-1/PD-L1 blockade. Furthermore, advancements in precision diagnostics, such as liquid biopsy-based detection of p53 mutations and AI-driven bioinformatics tools, enable early cancer identification and stratification of patients likely to benefit from targeted therapies. Therapeutic strategies targeting p53 pathways are rapidly evolving. Small molecules restoring wild-type p53 activity or disrupting mutant p53 interactions, such as APR-246 and MDM2 inhibitors, show promise in clinical trials. Combination approaches integrating gene editing with synthetic lethal strategies aim to exploit p53-dependent vulnerabilities. Additionally, leveraging p53′s immunomodulatory effects through vaccine development or adjuvants may enhance immunotherapy responses. In conclusion, deciphering p53′s complex biology underscores its unparalleled potential as a biomarker and therapeutic target. Integrating multi-omics analyses, functional genomic screens, and real-world clinical data will accelerate the translation of p53-focused research into precision oncology breakthroughs, ultimately improving patient outcomes. Full article

Marek’s disease (MD), induced by the highly contagious Marek’s disease virus (MDV), remains a significant challenge to global poultry health despite extensive vaccination efforts. This study employed integrated transcriptomic and metabolomic analyses to investigate liver responses in naturally MDV-infected Wenchang chickens during late infection stages. RNA sequencing identified 959 differentially expressed genes (DEGs) between the infected and uninfected groups. Functional enrichment analysis demonstrated that these DEGs were primarily associated with canonical pathways related to metabolism and cellular processes, including lipid, carbohydrate, and amino acid metabolism, as well as the p53 signaling pathway, cell cycle, and apoptosis. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) detected 561 differentially expressed metabolites (DEMs), showing near-significant enrichment (p = 0.069) in phenylalanine metabolism. Integrated analysis of transcriptomics and metabolomics data highlighted that critical gene–metabolite pairs such as SGPL1-palmitaldehyde–sphinganine-1-phosphate and ME1-NADP+–malic acid potentially mediate functional crosstalk between sphingolipid metabolism and cellular redox homeostasis during viral oncogenesis. This comprehensive mapping of regulatory networks provides insights into host–virus interactions during MDV pathogenesis, offering potential applications in immunomodulation approaches, targeted therapeutic strategies, and vaccine adjuvant development. Full article

Background/Objectives: The liver, the body’s primary detoxifying organ, is often affected by various inflammatory diseases, including hepatitis, cirrhosis, and non-alcoholic fatty liver disease (NAFLD), many of which can be exacerbated by secondary infections such as spontaneous bacterial peritonitis, bacteremia, and sepsis—particularly in patients with advanced liver dysfunction. The global rise in these conditions underscores the need for effective interventions. Natural products have attracted attention for their potential to support liver health, particularly through synergistic combinations of plant extracts. Epavin, a dietary supplement from Erbenobili S.r.l., formulated with plant extracts like Taraxacum officinale (L.), Silybum marianum (L.) Gaertn., and Cynara scolymus (L.), known for their liver-supporting properties, has been proposed as adjuvant for liver functions. The aim of this work was to evaluate of Epavin’s antioxidant, anti-inflammatory, and protective effects against heavy metal-induced toxicity. In addition, the antibacterial effect of Epavin against a panel of bacterial strains responsible for infections associated with liver injuries has been evaluated. Methods: The protection against oxidative stress induced by H₂O₂ was evaluated in HepG2 and BALB/3T3 cells using the dichlorofluorescein diacetate (DCFH-DA) assay. Its anti-inflammatory activity was investigated by measuring the reduction in nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages using the Griess assay. Additionally, the cytoprotecting of Epavin against heavy metal-induced toxicity and oxidative stress were evaluated in HepG2 cells using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] (MTT) and DCFH-DA assays. The antibacterial activity of Epavin was assessed by determining the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) against Gram-positive (Enterococcus faecalis ATCC 29212, and BS, Staphylococcus aureus 25923, 29213, 43300, and BS) and Gram-negative (Escherichia coli 25922, and BS, Klebsiella pneumoniae 13883, 70063, and BS) bacterial strains using the microdilution method in broth, following the Clinical and Laboratory Standards Institute’s (CLSI) guidelines. Results: Epavin effectively reduced oxidative stress in HepG2 and BALB/3T3 cells and decreased NO production in LPS-stimulated RAW 264.7 macrophages. Moreover, Epavin demonstrated a protective effect against heavy metal-induced toxicity and oxidative damage in HepG2 cells. Finally, it exhibited significant antibacterial activity against both Gram-positive and Gram-negative bacterial strains, with MIC values ranging from 1.5 to 6.0 mg/mL. Conclusions: The interesting results obtained suggest that Epavin may serve as a valuable natural adjuvant for liver health by enhancing detoxification processes, reducing inflammation, and exerting antibacterial effects that could be beneficial in the context of liver-associated infections. Full article

Background: Oral squamous cell carcinoma (OSCC) is one of the most serious forms of cancer in the world. The opportunities to decrease the mortality rate would lie in the possibility of earlier identification of this pathology, and at the same time, the immediate approach of anticancer therapy. Furthermore, new treatment strategies for OSCC are needed to improve existing therapeutic options. Bioactive compounds found in medicinal plants could be used to support these strategies. It is already known that they have an increased potential for action and a safety profile; therefore, they could improve the therapeutic effect of classical chemotherapeutic agents in combination therapies. Methodology: This research was based on an extensive review of recently published studies in scientific databases (PubMed, Scopus, and Web of Science). The selection criteria were based on experimental protocols investigating molecular mechanisms, synergistic actions with conventional anticancer agents, and novel formulation possibilities (e.g., nanoemulsions and mucoadhesive films) for the targeted delivery of bioactive compounds in OSCC. Particular attention was given to in vitro, in vivo, translational, and clinical studies that have proven therapeutic relevance. Results: Recent discoveries regarding the effect of bioactive compounds in the treatment of oral cancer were analyzed, with a view to integrating them into oncological practice for increasing therapeutic efficacy and reducing the occurrence of adverse reactions and treatment resistance. Conclusions: Significant progress has been achieved in this review, allowing us to appreciate that the valorization of these bioactive compounds is emerging. Full article

Outer-membrane vesicles (OMVs), naturally secreted by Gram-negative bacteria, have gained recognition as a versatile platform for the development of next-generation vaccines. OMVs are essential contributors to bacterial pathogenesis, horizontal gene transfer, cellular communication, the maintenance of bacterial fitness, and quorum sensing. Their intrinsic immunogenicity, adjuvant properties, and scalability establish OMVs as potent tools for combating infectious diseases and cancer. Recent advancements in genetic engineering and biotechnology have further expanded the utility of OMVs, enabling the incorporation of multiple epitopes and antigens from diverse pathogens. These developments address critical challenges such as antigenic variability and co-infections, offering broader immune coverage and cost-effective solutions. This review explores the unique structural and immunological properties of OMVs, emphasizing their capacity to elicit robust immune responses. It critically examines established and emerging engineering strategies, including the genetic engineering of surface-displayed antigens, surface conjugation, glycoengineering, nanoparticle-based OMV engineering, hybrid OMVs, and in situ OMV production, among others. Furthermore, recent advancements in preclinical research on OMV-based vaccines, including synthetic OMVs, OMV-based nanorobots, and nanodiscs, as well as emerging isolation and purification methods, are discussed. Lastly, future directions are proposed, highlighting the potential integration of synthetic biology techniques to accelerate research on OMV engineering. Full article

Skin cancers are associated with a significant psychological burden across all age groups, particularly as their global incidence continues to rise. Ultraviolet (UV) radiation—primarily UVA and UVB—remains the leading etiological factor, inducing DNA mutations in key genes such as TP53 and BRAF. Among skin cancers, basal cell carcinoma (BCC) is the most prevalent and typically indolent. In contrast, squamous cell carcinoma (SCC) tends to be more invasive, while melanoma is the most aggressive and prone to metastasis. Melanoma is especially concerning due to its rapid dissemination and its occurrence not only on the skin but also in ocular, mucosal, and nail tissues. These challenges, along with rising treatment resistance and mortality, underscore the urgent need for novel anticancer agents. Berberine—a plant-derived isoquinoline alkaloid—has attracted increasing attention for its broad-spectrum anticancer potential, including against skin cancers. In this review, we summarize current evidence regarding berberine’s mechanisms of action in melanoma and SCC, emphasizing both its preventive and therapeutic effects. We further explore its potential as an adjuvant agent in combination with conventional treatments, offering a promising avenue for enhancing the clinical outcomes of skin cancer therapy. Full article

Being one of the most aggressive primary brain tumors, glioblastoma multiforme (GBM) is known from the median survivals of just 15 months following diagnosis. Conventional treatments, including surgical resection, radiotherapy, and chemotherapy, have limited efficiency due to the invasive nature of glioma cells and the presence of a blood–brain barrier. Therefore, adjuvant therapy in the form of a localized delivery of chemotherapeutic agents is indispensable to increase the chances of patients. Among a variety of advanced drug carriers, collagen has recently emerged as an excellent choice for regional chemotherapy, mainly due to its biocompatibility, biodegradability, weak antigenicity, biomimetics, and well-known safety profile, as well as its native presence in the extracellular matrix of the central nervous system. The aim of this paper is to highlight the most recent studies describing the application of collagen as a drug carrier able to provide an extended delivery of chemotherapeutic agents directly to the GBM site, and to provide exciting opportunities for its future applications. Full article

Background: Vaccines have revolutionized disease prevention, yet their effectiveness is challenged by variable immunogenicity, individual response differences, and emerging variants. Biomimetic strategies, inspired by natural immune processes, offer new avenues to enhance vaccine performance. Objectives: This narrative review examines how bioinspired approaches—grounded in evolutionary medicine, immunology, and host–microbiota interactions—can improve vaccine immunogenicity and long-term protection. We further examine the evolutionary foundations of immune responses, highlighting how an evolutionary perspective can inform the development of durable, broadly protective, and personalized vaccines. Furthermore, mechanistic insights at the molecular and cellular level are explored, including Toll-like receptor (TLR) engagement, dendritic cell activation pathways, and MHC-I/MHC-II-mediated antigen presentation. These mechanisms are often mimicked in biomimetic systems to enhance uptake, processing, and adaptive immune activation. Results: The review highlights how immunosenescence, maternal immunity, genetic variation, and gut microbiota composition influence vaccine responses. Biomimetic platforms—such as nanoparticle carriers and novel adjuvants—enhance antigen presentation, boost adaptive immunity, and may overcome limitations in traditional vaccine approaches. Additionally, co-administration strategies, delivery systems, and microbiota-derived immunomodulators show promise in improving vaccine responsiveness. Conclusions: Integrating biomimetic and evolutionary principles into vaccine design represents a promising path toward safer, longer-lasting, and more effective immunizations Full article

Helicobacter pylori (H. pylori) is one of the most prevalent chronic bacterial infections globally, significantly contributing to gastritis, peptic ulcers, and gastric malignancies. Its pathogenesis involves a complex array of virulence factors—including cagA, vacA, and urease—which facilitate mucosal colonization, immune evasion, and persistent inflammation. A major challenge in vaccine development is the bacterium’s ability to manipulate both innate and adaptive immune responses, resulting in limited natural clearance and long-term persistence. This review synthesizes H. pylori pathogenesis and host immune dynamics, highlighting their implications for vaccine design. By elucidating the molecular and cellular mechanisms underlying host–pathogen interactions, we explore how these insights inform antigen selection, adjuvant optimization, and delivery strategies. By integrating basic science with translational objectives, this review aims to support the development of an effective H. pylori vaccine, addressing global health needs, particularly in regions with a high infection burden and limited access to treatment. Full article

Goblet cell adenocarcinomas (GCAs) are an exceedingly rare subtype of tumors, almost exclusively occurring in the appendix, and characterized by features overlapping both adenocarcinomas and neuroendocrine tumors (NETs), which has historically led to confusion and varied nomenclature. This study presents a comprehensive review of the literature highlighting particularities of this type of malignancy, starting from a rare case of a 54-year-old female operated on in our clinic for an appendiceal tumor, initially suspected to be a mucinous neoplasm based on colonoscopic biopsy, which was ultimately confirmed to be goblet cell adenocarcinoma on both intraoperative frozen section and definitive pathological examination. Exhibiting signs and symptoms associated with an abdominal mass, she underwent a right hemicolectomy with partial omentectomy for locally advanced, high-grade, invasive goblet cell adenocarcinoma of the appendix with lymphatic macro metastases and epiploic invasion, categorized as AJCC stage IVb carcinomatosis. The patient received FOLFOX adjuvant. Six months later, she required reoperation due to the progression of carcinomatosis, which was again confirmed histopathologically. A second-line oncological protocol comprising irinotecan, capecitabine, and bevacizumab was initiated. Given the rarity of GCAs and the absence of a consensus on nomenclature, classification, and diagnostic criteria, we conducted a comprehensive literature review to highlight current trends related to this entity, including its classification within different systems (Tang, Yozu, WHO, AJCC), as well as the therapeutic surgical approaches—ranging from simple appendectomy to extensive multiorgan resection, cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC), and the use of systemic therapy. Adhering to these recommendations will enhance communication among pathologists, surgeons, and oncologists regarding the natural history and prognosis of this rare malignancy. Full article

The increasing prevalence of antimicrobial resistance (AMR) demands novel strategies, including the use of plant-derived agents. This study investigates the chemical profile and in vitro antimicrobial activity of essential oil from Lavandula angustifolia (LEO), cultivated in Northeastern Bulgaria. Gas chromatography–mass spectrometry (GC-MS) analysis confirmed the presence of a linalool/linalyl acetate chemotype, characteristic of high-quality lavender oil. LEO demonstrated significant inhibitory activity against Escherichia coli ATCC 25922, with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 0.31% (v/v) and moderate to weak activity against other Gram-positive and fungal strains. Time–kill assays revealed a concentration-dependent bactericidal effect on E. coli. The addition of LEO at subinhibitory concentrations increased the inhibition zones for all antibiotics. In silico analysis identified functional protein clusters potentially modulated by LEO constituents, including targets related to membrane integrity and metabolic regulation. The findings indicate the potential of lavender essential oil as a natural antimicrobial adjuvant; however, additional in vivo and clinical investigations are necessary to validate its therapeutic use. Furthermore, molecular docking analysis revealed a high binding affinity of linalool and linalyl acetate towards the FabI protein of E.coli, suggesting a potential inhibitory mechanism at the molecular level. Full article

Background: Vaccines represent one of the most affordable and efficient tools for controlling infectious diseases; however, the development of efficacious vaccines against complex pathogens remains a major challenge. Adjuvants play a relevant role in enhancing vaccine-induced immune responses. One such molecule is interferon-stimulated gene 15 (ISG15), a key modulator of antiviral immunity that acts both through ISGylation-dependent mechanisms and as a cytokine-like molecule. Methods: In this study, we assessed the immunostimulatory potential of ISG15 as an adjuvant in Modified Vaccinia virus Ankara (MVA)-based vaccine candidates targeting Zika virus (ZIKV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Early innate responses and immune cell infiltration were analyzed in immunized mice by flow cytometry and cytokine profiling. To elucidate the underlying mechanism of action of ISG15, in vitro co-infection studies were performed in macrophages. Finally, we evaluated the magnitude and functional quality of the elicited antigen-specific cellular immune responses in vivo. Results: Analysis of early innate responses revealed both platform- and variant-specific effects. ISG15AA preferentially promoted natural killer (NK) cell recruitment at the injection site, whereas ISG15GG enhanced myeloid cell infiltration in draining lymph nodes (DLNs), particularly when delivered via MVA. Moreover, in vitro co-infection of macrophages with MVA-based vaccine vectors and the ISG15AA mutant led to a marked increase in proinflammatory cytokine production, highlighting a dominant role for the extracellular, ISGylation-independent functions of ISG15 in shaping vaccine-induced immunity. Notably, co-infection of ISG15 with MVA-ZIKV and MVA-SARS-CoV-2 vaccine candidates enhanced the magnitude of antigen-specific immune responses in both vaccine models. Conclusions: ISG15, particularly in its ISGylation-deficient form, acts as a promising immunomodulatory adjuvant for viral vaccines, enhancing both innate and adaptive immune responses. Consistent with previous findings in the context of Human Immunodeficiency virus type 1 (HIV-1) vaccines, this study further supports the potential of ISG15 as an effective adjuvant for vaccines targeting viral infections such as ZIKV and SARS-CoV-2. Full article