Search Results (67)

Heracleum sosnowskyi Manden., or H. sosnowskyi, of the Apiaceae was first cultivated in the USSR in 1947 as a potential fodder plant. Due to the development of cold-resistant cultivars and the characteristics of H. sosnowskyi, it quickly became feral. As a result, H. sosnowskyi began to spread as an aggressive invasive species in the 1970s and 1980s. By the 90s it had become an ecological disaster. As well as forming monocultures and displacing native species, H. sosnowskyi contains furanocoumarins, photosensitizing compounds that increase skin sensitivity to ultraviolet rays and cause severe burns. In addition, furanocoumarins have cytotoxic, genotoxic, mutagenic and estrogenic effects. H. sosnowskyi also contains essential oils, which are particularly active during flowering and can irritate the mucous membranes of the eyes and respiratory tract, as well as cause allergic reactions in the form of bronchospasm in people with asthma and hypersensitivity. When released in high concentrations, these biologically active compounds have an allelopathic effect on native plant species, displacing them and reducing biodiversity. As H. sosnowskyi is not native; the biologically active compounds it secretes have a xenobiotic effect, causing serious damage to the ecosystems it occupies. However, in parallel with these negative properties, furanocoumarins have been found to be effective in the treatment of cancer and skin diseases. Furanocoumarins possess antimicrobial antioxidant osteo- and neuroprotective properties. Essential oils containing octyl acetate, carboxylic acid esters, and terpenes can be used in the pharmaceutical industry as antiseptic and anti-inflammatory agents. Additionally, essential oils can be used as biofumigants and natural herbicides. A comprehensive approach allows H. sosnowskyi to be viewed in two ways. On the one hand, it is an aggressive alien species that causes significant damage to ecosystems and poses a threat to human health. On the other hand, it is a potentially valuable natural resource whose biomass can be used within the principles of the circular economy. It is hoped that the use of H. sosnowskyi for economic interests can be a partial compensation for the problem of its aggressive invasion, which is of anthropogenic origin. Full article

Background/Objectives: The aim of this study was to investigate the cytotoxic, genotoxic, apoptotic, and anti-inflammatory effects of the antiseptic agent octenidine dihydrochloride (OCT-D) on the RPMI-2650 cell line derived from human nasal mucosa in vitro. Methods: RPMI-2650 cells and Human Umbilical Cord Endothelial Cells (HUVECs) were treated with various concentrations of OCT-D (0.00625–0.4%) for 12 and 24 h. Cell viability was assessed using the WST-1 assay, while DNA damage was assessed using the comet and micronucleus (MN) assays. Apoptotic activity was determined using Annexin V flow cytometry and fluorescence microscopy. Intracellular reactive oxygen species (ROS) levels were measured, and inflammatory cytokines (IL-1β, IL-6, TNF-α, and IFN-γ) were measured by Enzyme-Linked Immunosorbent Assay (ELISA). The mRNA expression of genes associated with apoptosis, oxidative stress, and inflammation was analyzed using RT-PCR. Results: OCT-D caused dose- and time-dependent cytotoxicity, and RPMI-2650 cells showed greater resistance compared to HUVECs. While a strong apoptotic response was observed in HUVECs, RPMI-2650 cells exhibited limited apoptosis. OCT-D was found to cause dose-dependent DNA damage and an increase in MN in both cell lines. OCT-D significantly reduced cytokine levels and ROS production in both cell types. RT-PCR results supported its anti-inflammatory and antioxidant effects at the molecular level. Conclusions: In conclusion, this study demonstrated that OCT-D exhibited minimal cytotoxic and apoptotic effects in RPMI-2650 cells, but affected vascular structure by inducing apoptosis in endothelial cells. These findings provide important evidence that OCT-D can be used as a potential adjunctive agent in nasal treatments, and these data need to be supported by preclinical and clinical studies. Full article

The DNA Damage Response (DDR) network is an essential machinery for maintaining genomic integrity, with DDR defects being implicated in cancer initiation, progression, and treatment resistance. Moreover, oxidative stress, an imbalance between reactive oxygen species production and antioxidant defense, can significantly impact cell viability, leading to cell death or survival. Herein, we tested the hypothesis that DDR-related signals and redox status measured in multiple myeloma (MM) cell lines correlate with the sensitivity to genotoxic insults. At baseline and following irradiation with Ultraviolet C (UVC; 50 J/m²) or treatment with melphalan (100 μg/mL for 5 min) DDR-related parameters, redox status expressed as GSH/GSSG ratio and apurinic/apyrimidinic sites were evaluated in a panel of eleven human MM cell lines and one healthy B lymphoblastoid cell line. We found that MM cell lines with increased apoptosis rates displayed significantly higher levels of endogenous/baseline DNA damage, reduced GSH/GSSG ratio, augmented apurinic/apyrimidinic lesions, decreased nucleotide excision repair and interstrand crosslinks repair capacities, and highly condensed chromatin structure. Taken together, these findings demonstrate that DDR-related parameters and redox status correlate with the sensitivity of MM cells to DNA-damaging agents, specifically melphalan, and, if further validated, may be exploited as novel sensitive/effective biomarkers. Full article

Cholangiocarcinoma (CCA) is an aggressive malignancy of the biliary tract with rising global incidence and limited treatment options. Its pathogenesis involves a complex interplay of genetic mutations, epigenetic dysregulation, inflammatory signaling, and environmental influences. Emerging evidence highlights the pivotal role of the gut–liver axis and microbiota dysbiosis in shaping biliary homeostasis and disease progression. Alterations in microbial composition disrupt apoptosis and autophagy, two key processes regulating cell survival and death, thereby contributing to tumorigenesis, metastasis, and therapy resistance. Specific taxa, including Enterococcus, Escherichia coli, Pseudomonas, Bifidobacterium, and Bacillus, demonstrate strain-dependent effects, acting either as tumor promoters through genotoxic metabolites and immune evasion or as potential tumor suppressors by inducing apoptosis and immune activation. These findings underscore the context-dependent roles of microbiota in CCA biology. Importantly, microbiota modulation offers novel therapeutic opportunities. Dietary interventions such as probiotics, prebiotics, and nutritional strategies, alongside innovative microbiome-targeted therapies, hold promise for restoring microbial balance, enhancing antitumor immunity, and improving patient outcomes. This review integrates current molecular and microbiological evidence to propose the gut microbiota as both a biomarker and a therapeutic target in CCA, opening avenues for precision medicine approaches in hepatobiliary oncology. Full article

Acute promyelocytic leukemia (APL) is a rare subtype of acute myeloid leukemia (AML) characterized by chromosomal translocation forming the fusion protein that blocks the differentiation of myeloid progenitors and increases the self-renewal of leukemia cells. The introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has dramatically improved outcomes in APL, making it a leading example of successful treatment through differentiation of cancer cells. However, life-threatening side effects and treatment resistance may develop; therefore, modulation of the safety and efficacy of these drugs may contribute to further improving treatment results. Recently, zinc, involved in the structure and function of transcription factors, has received special attention for its potential role in the development and treatment response of cancer. Zinc homeostasis is disrupted in APL, with intracellular accumulation stabilizing oncogenic proteins. Zinc depletion promotes degradation of PML–RARA and induces apoptosis, while supplementation enhances genotoxic stress in leukemic cells but protects normal hematopoiesis. Zinc also regulates key transcription factors involved in differentiation and proliferation, including RUNX2, KLF4, GFI1, and CREB. In this review, we examine how zinc may impact zinc-finger (ZnF) and non-ZnF transcription factors and differentiation therapy in APL, thereby identifying potential strategies to enhance treatment efficacy and minimize side effects. 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

The treatment of proctological conditions, including hemorrhoids, anal fissures, and perianal abscesses, is often complicated by bacterial infections, particularly those involving multidrug-resistant Escherichia coli. This study presents the synthesis, characterization, and biological evaluation of the newly designed synthetic peptide AMPEC4, inspired by cytotoxin 5 from Naja ashei snake venom. AMPEC4 demonstrated potent antimicrobial properties with MIC values of 100 and 200 µg/mL, effectively inhibiting biofilm formation (up to 84%) and eradicating the pre-formed biofilm by up to 35%. The antibacterial activity of AMPEC4 was further supported by a membrane permeabilization assay, demonstrating its capacity to disrupt bacterial membrane integrity in a dose-dependent manner. Furthermore, AMPEC4 significantly promoted fibroblast migration, a critical step in tissue regeneration, while exhibiting notable biocompatibility, as evidenced by the absence of hemolytic, cytotoxic, and genotoxic effects. By addressing both infection control and tissue regeneration, AMPEC4 represents a promising therapeutic strategy for managing chronic wounds, particularly in the challenging environment of the anorectal region. Its ability to target Escherichia coli reference and clinical strains while accelerating the wound-healing process underscores its potential for future clinical applications. Full article

Ocular fungal infections are slow-progressing conditions that primarily affect the cornea but can also involve the entire eyeball. Candida albicans is one of the most involved species. Both diagnosing and treating these infections require prompt and effective action. However, the currently available treatment options mainly rely on azoles and polyenes, which are known for their poor penetration into ocular tissue and associated toxicity. Moreover, conventional antifungals are usually ineffective when tested against biofilm-associated infections, mainly due to the metabolically inactive state of dormant cells embedded in the extracellular biofilm matrix. Here, analysis of the in vitro antifungal activity of four 2-aminobenzoic acid derivatives synthesized using a green method and their combination with Fluconazole (FLC) showed efficacy against the FLC-resistant clinical isolate of C. albicans under both planktonic and biofilm formation conditions. Results showed that compounds 1 and 2 exhibited the best antifungal activity in the checkerboard association test, presenting a synergistic effect towards antifungal action. The downregulation of HWP, ERG11, and ASL3 genes during biofilm inhibition suggested a reduced capacity of the four compounds for hyphal growth and adhesion, as well as a decrease in pathogenicity due to the downregulation of some SAP genes. In vitro and in vivo toxicity profiles indicated that these compounds exhibited low toxicity, as well as the absence of genotoxic effects. Therefore, green-synthetized 2-aminobenzoic acid derivatives may have potential as antifungal agents for the inhibition of C. albicans growth and biofilm formation. Full article

The prevention of human infectious diseases associated with waterborne pathogens is reliant on the effective disinfection of water supplies by drinking water treatment plants and adequately maintained distribution networks. For decades, the chlorination of water has safeguarded public health, where chlorine is broadly applied in both water disinfection and food production facilities, including the dairy industry, from farm to fork. The identification of chlorine disinfection byproducts in water supplies and dairy food produce is of great concern, however, due to their cytotoxic, genotoxic, mutagenic, teratogenic, and potential endocrine-disrupting activity. The association between the trihalomethanes (THMs) and haloacetic acids (HAAs) and tumour formation is documented and has led to the implementation of maximum contaminant levels enforced by the European Union. Furthermore, chlorine resistance in bacterial species is associated with multidrug resistance in clinically relevant pathogens, where antibiotic- and biocidal-resistant genes are also environmental pollutants. Increasing the concentration of chlorine to surmount this resistance will ultimately lead to increasing concentrations of byproducts in both water and food products, exceeding the EU requirements. This article provides insight into chlorine DBPs as a toxicological public health risk and the relationship between chlorine resistance and antibiotic resistance in microbes relevant to dairy food production. Full article

Background/Objectives: Neuroblastoma is a genetically diverse, highly metastatic pediatric cancer accounting for 15% of childhood cancer deaths despite only having ~8% of childhood cancer incidence. The current standard of care for high-risk diseases is highly genotoxic. This, combined with less than 50% survival in high-risk diseases and an abysmal 5% survival in relapsed cases, makes discovering novel, effective, and less toxic treatments essential. Methods: A prophylactic syngeneic mouse model was used to test high-dose lipid-mediator highly unsaturated fatty acids on tumorigenesis. Wildtype mice were gavaged with 12.3–14.6 g/d (adult human equivalent) omega-3 EPA, DHA, or oxidation-resistant bis allylic deuterated DHA (D-DHA) and 4.6–6.0 g/d arachidonic acid (ARA). At seven days, MYCN-expressing murine neuro-2a cells syngeneic to the gavaged mice were injected subcutaneously. Oral gavage continued for 10–20 d post-injection when tumors and tissues were harvested. Results: Fifty percent of control (not gavaged) animals form tumors (4/8) at about 10 d. High-dose DHA, D-DHA, and EPA block tumor formation completely in n = 8 or 10 animals. In contrast, ω6 arachidonic acid (4.6–6.0 g/d) enhances tumor formation (6/10 tumors) and reduces latency (5.5 to 10 days) compared to the control. The co-delivery of ARA and EPA results in a reduced tumor burden analogous to the control group, suggesting that EPA directly opposes the mechanism of ARA-mediated tumor formation. DHA acts through a non-oxidative mechanism. Conclusions: Sustained high-dose ω3 (weeks/months) is safe and well-tolerated in humans. These results suggest that ω3 DHA and EPA delivery at ultra-high doses may represent a viable low-toxicity therapy for neuroblastoma. Full article

Heterocyclic pharmaceuticals are emerging contaminants due to their toxic, carcinogenic nature and detrimental impact on the natural ecosystem. These compounds pose a significant environmental concern given their widespread use in medical therapy, constituting over 90% of new medications. Their unique chemical structure contributes to their persistence in various environmental matrices, necessitating urgent measures to mitigate their risks. This review comprehensively examines the sources, environmental fate, toxicity, and long-term risks associated with heterocyclic pharmaceuticals, proposing potential remediation strategies. The article commences with an overview of the diverse types of heterocyclic pharmaceuticals and their applications, focusing on compounds containing heteroatoms such as nitrogen, oxygen, and sulfur. Subsequently, it explores the sources and pathways through which these pollutants enter the environment, including wastewater discharge, agricultural runoff, improper disposal, resistance to biodegradation, and bioaccumulation. The toxic effects and long-term consequences of exposure to heterocyclic pharmaceuticals are then discussed, encompassing neurotoxicity, genotoxicity, mutagenesis, cardiovascular and metabolic toxicity, carcinogenicity, and teratogenesis. Additionally, this review summarizes various remediation strategies and treatment solutions aimed at reducing the environmental impact of these compounds, drawing insights from the literature. The research concludes by identifying critical areas for future research, emphasizing the urgent need for more effective remediation strategies to address the growing concern posed by these emerging contaminants. Full article

The present study investigates the influence of nitrosamines and etoposide on mesenchymal stromal cells (MSCs) in a differentiation state- and biological age-dependent manner. The genotoxic effects of the agents on both neonatal and adult stem cell populations after treatment, before, or during the course of differentiation, and the sensitivity of the different MSC types to different concentrations of MNU or etoposide were assessed. Hereby, the multipotent differentiation capacity of MSCs into osteoblasts, adipocytes, and chondrocytes was analyzed. Our findings reveal that while all cell types exhibit DNA damage upon exposure, neonatal CB-USSCs demonstrate enhanced resistance to genotoxic damage compared with their adult counterparts. Moreover, the osteogenic differentiation of MSCs was more susceptible to genotoxic damage, whereas the adipogenic and chondrogenic differentiation potentials did not show any significant changes upon treatment with genotoxin. Furthermore, we emphasize the cell-specific variability in responses to genotoxic damage and the differences in sensitivity and reaction across different cell types, thus advocating the consideration of these variabilities during drug testing and developmental biological research. Full article

Background: Breast cancer incidence and mortality exhibit a rising trend globally among both premenopausal and postmenopausal women, suggesting that there are serious errors in our preventive and therapeutic measures. Purpose: Providing a series of valuable, but misunderstood inventions highlighting the role of increasing estrogen signaling in prevention and therapy of breast cancer instead of its inhibition. Results: 1. Breast cells and breast cancer cells with germline BRCA1/2 mutations similarly show defects in liganded estrogen receptor (ER) signaling, demonstrating its role in genomic instability and cancer initiation. 2. In breast tumors, the increased expression of special receptor family maybe an effort for self-directed improvement of genomic defects, while the weakness or loss of receptors indicates a defect requiring medical repair. 3. ER overexpression in breast cancer cells is capable of strengthening estrogen signaling and DNA repair, while in ER negative tumors, HER2 overexpression tries to upregulate unliganded ER activation and genome stabilization. 4. ER-positive breast cancers responsive to endocrine therapy may show a compensatory ER overexpression resulting in a transient tumor response. Breast cancers non-responsive to antiestrogen treatment exhibit HER2-overexpression for compensating the complete inhibition of hormonal ER activation. 5. In breast tumors, somatic mutations serve upregulation of ER activation via liganded or unliganded pathway helping genome stabilization and apoptotic death. 6. The mutual communication between breast cancer and its inflammatory environment is a wonderful partnership among cells fighting for genome stabilization and apoptotic death of tumor. 7. In breast cancers, there is no resistance to genotoxic or immune blocker therapies, but rather, the nonresponsive tumor cells exhaust all compensatory possibilities against therapeutic damages. Conclusions: Understanding the behavior and ambition of breast cancer cells may achieve a turn in therapy via applying supportive care instead of genotoxic measures. Full article

Ciprofloxacin, a second-generation fluoroquinolone, is widely used in human and veterinary medicine. However, it is known for its environmental persistence and ability to promote bacterial resistance, causing genotoxic impacts and chronic toxicity in various aquatic life forms. Adsorption is an effective technique for water treatment, removing multiple organic molecules, even in minimal concentrations. Hybrid materials based on fibrous clay minerals, such as palygorskite, are promising for environmental remediation, significantly when modified with oxides to improve their adsorption properties. This work prepared and characterized a CeO₂/palygorskite hybrid material using various physicochemical techniques (XRD, FTIR, BET, SEM), which indicated the formation of the heterostructure material with interesting textural properties. This CeO₂/palygorskite was evaluated as an adsorbent of the antibiotic drug ciprofloxacin. The influence of pH (3, 7, and 9) and ciprofloxacin concentration (6, 8, 10, and 14 ppm) on adsorption were studied, using pseudo-first- and pseudo-second-order kinetic models. The pseudo-second-order model showed the best fit (R² > 0.99) and the lowest squared error (SSE), indicating chemisorption. The Langmuir, Freundlich, and Temkin isotherms were applied to the experimental data, where the Langmuir model had the best fit, indicating monolayer adsorption with a maximum capacity of 15 mg·g⁻¹. Post-adsorption characterization by FTIR confirmed the structural stability of the material, highlighting its promising application in environmental remediation due to its high concentration of adsorbents. Full article

Epitranscriptomics is a field that delves into post-transcriptional changes. Among these modifications, the conversion of adenosine to inosine, traduced as guanosine (A>I(G)), is one of the known RNA-editing mechanisms, catalyzed by ADARs. This type of RNA editing is the most common type of editing in mammals and contributes to biological diversity. Disruption in the A>I(G) RNA-editing balance has been linked to diseases, including several types of cancer. Drug resistance in patients with cancer represents a significant public health concern, contributing to increased mortality rates resulting from therapy non-responsiveness and disease progression, representing the greatest challenge for researchers in this field. The A>I(G) RNA editing is involved in several mechanisms over the immunotherapy and genotoxic drug response and drug resistance. This review investigates the relationship between ADAR1 and specific A>I(G) RNA-edited sites, focusing particularly on breast cancer, and the impact of these sites on DNA damage repair and the immune response over anti-cancer therapy. We address the underlying mechanisms, bioinformatics, and in vitro strategies for the identification and validation of A>I(G) RNA-edited sites. We gathered databases related to A>I(G) RNA editing and cancer and discussed the potential clinical and research implications of understanding A>I(G) RNA-editing patterns. Understanding the intricate role of ADAR1-mediated A>I(G) RNA editing in breast cancer holds significant promise for the development of personalized treatment approaches tailored to individual patients’ A>I(G) RNA-editing profiles. Full article