Search Results (10)

Multidrug-resistant bacterial pathogens pose a critical global health challenge, necessitating safe and effective antimicrobial alternatives. Plant-derived nanoparticles represent promising candidates due to their bioactivity and biocompatibility. Magnesium nitrate nanoparticles were synthesized using Momordica charantia peel extract through green chemistry. Phytochemical screening identified flavonoids, phenolics, tannins, and terpenoids that facilitated nanoparticle formation and stability. Characterization via scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, and Fourier transform infrared spectroscopy confirmed polydisperse size distribution (1–100 nm), crystalline structure, and functional group capping. Disc diffusion assays demonstrated concentration-dependent antibacterial activity against multidrug-resistant strains, with maximum inhibition zones of 17.6 ± 1.1 mm against Gram-positive bacteria. Minimum inhibitory concentration and minimum bactericidal concentration assays revealed high bactericidal activity, particularly against Gram-positive bacteria. Time-kill kinetic studies showed concentration- and time-dependent killing with ≥3 log₁₀ reduction in viable bacterial counts at higher concentrations. Nanoparticle–antibiotic combinations exhibited markedly enhanced activity against multidrug-resistant strains compared to free antibiotics, indicating synergistic effects. Toxicity assessment using Brine Shrimp Lethality Assay revealed low toxicity (LC₅₀ > 1000 µg/mL). Green-synthesized magnesium nitrate nanoparticles demonstrate potent antibacterial properties and effectively enhance antibiotic potency against multidrug-resistant bacteria. Further studies are required to validate therapeutic applicability. Full article

This study developed and evaluated multifunctional Cu-doped Zeolitic Imidazolate Framework-8 nanoparticles coated with hyaluronic acid (Cu-ZIF-8@HA) for antimicrobial application on stainless-steel food-contact surfaces. Structural characterization through SEM, TEM, and elemental mapping confirmed the successful synthesis, uniform Cu incorporation, and HA coating without compromising the crystalline ZIF-8 framework. Cu doping reduced particle size (~130 nm) and enhanced redox activity, while HA encapsulation improved colloidal stability and biocompatibility by shifting zeta potential from positive (+22.1 mV) to negative (−18.7 mV). Cytotoxicity assays demonstrated that HA significantly mitigated metal-induced toxicity, maintaining >70% cell viability at ≤1000 µg/mL. Antibacterial assessments revealed potent activity against Salmonella Typhimurium ATCC 14028 and Escherichia coli O157:H7, with Cu-ZIF-8@HA exhibiting the largest inhibition zones (18.15–20.33 mm), lowest MIC/MBC values (500/2000 µg/mL and 1000/2500 µg/mL), and over 6-log reductions in bacterial adhesion on stainless steel. Enhanced wettability (contact angle 11.77°) and surface energy (64.42 mN/m) further facilitated antimicrobial contact. These results confirm that Cu-ZIF-8@HA integrates the oxidative potency of Cu, the structural stability of ZIF-8, and the biocompatibility of HA, offering a promising and safe nanomaterial platform for controlling bacterial contamination and biofilm formation in food-processing environments. Full article

Background/Objectives: The stimulator of interferon genes (STING) pathway plays a central role in innate immune signaling and represents an attractive therapeutic target for cancer immunotherapy. Amidobenzimidazole (ABZI) derivatives have emerged as promising non-nucleotide STING agonists with improved drug-like properties compared to cyclic dinucleotides. However, current ABZI compounds still exhibit limited oral bioavailability and cross-species potency discrepancies. In addition, potential systemic toxicity remains a concern, indicating the need for further structural optimization. Methods: In this study, a comprehensive computer-aided drug design strategy was employed to systematically investigate ABZI derivatives and identify novel STING agonists with enhanced activity and favorable pharmacokinetic profiles. A 3D quantitative structure–activity relationship (3D-QSAR) model was constructed using the Topomer CoMFA approach based on a dataset of 109 reported ABZI compounds. Guided by the contour map analysis, new chemical groups were introduced through a fragment growth method, generating a large virtual library. The library was subsequently filtered via molecular docking, molecular dynamics simulations, and MM-PBSA binding free energy calculations. Results: Among the newly designed ABZI compounds, five compounds displayed lower binding free energies than D59, with M13 and M44 showing reductions exceeding 6.7 kcal/mol. This work demonstrates the effectiveness of an integrated in silico design strategy for the discovery of novel STING agonists. Conclusions: The identified compounds represent promising candidates for subsequent experimental validation and may support the development of nitrogen heterocycle-based STING agonists for antitumor applications. Full article

Mycotoxins are toxic compounds found in food and feed that pose significant risks to human and animal health. This work reviews recent studies on the cytotoxic effects of four mycotoxins: beauvericin (BEA), citrinin (CTN), moniliformin (MON), and patulin (PAT) in various cell lines. Additionally, an experimental study evaluates the effects of these mycotoxins and their binary combinations on human neuroblastoma cells (SH-SY5Y) after 24 and 48 h of exposure using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. This analysis is driven by the additional risks posed by the frequent occurrence of these combinations in agricultural and food products, as well as the lack of studies addressing their effects, interactions, and regulatory frameworks. This research focuses on comparing the cytotoxicity data obtained in the SH-SY5Y cell line with previously reported findings in the literature for other cell lines exposed to BEA, CTN, MON, and PAT, individually and in binary combination. The literature highlights significant scientific interest in understanding the cytotoxic effects of these mycotoxins, with findings varying based on exposure time and concentration. Experimentally, PAT demonstrated the highest toxicity in SH-SY5Y cells, while MON was the least toxic. Among combinations, BEA + MON and CTN + PAT showed the greatest reduction in cell viability. However, medium inhibitory concentration (IC₅₀) values were not reached for most combinations involving MON, reflecting its lower potency under the studied conditions. These findings underscore the importance of further investigation and enhanced regulations to address the health risks posed by mycotoxins, as their cytotoxic effects remain a pressing issue in food safety. Full article

Colchicine (COL), a widely used natural drug, has potent anti-inflammatory effects; however, as a narrow therapeutic index drug, its clinical application is limited by its serious gastrointestinal adverse effects, and only oral formulations are currently marketed worldwide. Recent studies have shown that transdermal, injection, and oral drug delivery are the three main delivery strategies for COL. This article elaborates on the research progress of different delivery strategies in terms of toxicity reduction and efficacy enhancement, depicting that the transdermal drug delivery route can avoid the first-pass effect and the traumatic pain associated with the oral and injection routes, respectively. Therefore, such a dosage form holds a significant promise that requires the development of further research to investigate effective COL delivery formulations. In addition, the permeation-promoting technologies utilized for transdermal drug delivery systems are briefly discussed. This article is expected to provide scientific ideas and theoretical guidance for future research and the exploration of COL delivery strategies. Full article

Bexarotene, a drug approved for treatment of cutaneous T-cell lymphoma (CTCL), is classified as a rexinoid by its ability to act as a retinoid X receptor (RXR) agonist with high specificity. Rexinoids are capable of inducing RXR homodimerization leading to the induction of apoptosis and inhibition of proliferation in human cancers. Numerous studies have shown that bexarotene is effective in reducing viability and proliferation in CTCL cell lines. However, many treated patients present with cutaneous toxicity, hypothyroidism, and hyperlipidemia due to crossover activity with retinoic acid receptor (RAR), thyroid hormone receptor (TR), and liver X receptor (LXR) signaling, respectively. In this study, 10 novel analogs and three standard compounds were evaluated side-by-side with bexarotene for their ability to drive RXR homodimerization and subsequent binding to the RXR response element (RXRE). In addition, these analogs were assessed for proliferation inhibition of CTCL cells, cytotoxicity, and mutagenicity. Furthermore, the most effective analogs were analyzed via qPCR to determine efficacy in modulating expression of two critical tumor suppressor genes, ATF3 and EGR3. Our results suggest that these new compounds may possess similar or enhanced therapeutic potential since they display enhanced RXR activation with equivalent or greater reduction in CTCL cell proliferation, as well as the ability to induce ATF3 and EGR3. This work broadens our understanding of RXR–ligand relationships and permits development of possibly more efficacious pharmaceutical drugs. Modifications of RXR agonists can yield agents with enhanced biological selectivity and potency when compared to the parent compound, potentially leading to improved patient outcomes. Full article

Low phosphorus (P) availability is a major limiting factor for potatoes. P fertilizer is applied to enhance P availability; however, it may become toxic when plants accumulate at high concentrations. Therefore, it is necessary to gain more knowledge of the morphological and biochemical processes associated with P deficiency and toxicity for potatoes, as well as to explore an alternative approach to ameliorate the P deficiency condition. A comprehensive study was conducted (I) to assess plant morphology, mineral allocation, and metabolites of potatoes in response to P deficiency and toxicity; and (II) to evaluate the potency of plant growth-promoting rhizobacteria (PGPR) in improving plant biomass, P uptake, and metabolites at low P levels. The results revealed a reduction in plant height and biomass by 60–80% under P deficiency compared to P optimum. P deficiency and toxicity conditions also altered the mineral concentration and allocation in plants due to nutrient imbalance. The stress induced by both P deficiency and toxicity was evident from an accumulation of proline and total free amino acids in young leaves and roots. Furthermore, root metabolite profiling revealed that P deficiency reduced sugars by 50–80% and organic acids by 20–90%, but increased amino acids by 1.5–14.8 times. However, the effect of P toxicity on metabolic changes in roots was less pronounced. Under P deficiency, PGPR significantly improved the root and shoot biomass, total root length, and root surface area by 32–45%. This finding suggests the potency of PGPR inoculation to increase potato plant tolerance under P deficiency. Full article

The 18 kDa translocator protein (TSPO) plays an important role in apoptotic cell death, including apoptosis induced by the hypoxia mimicking agent cobalt chloride (CoCl₂). In this study, the protective effects of a high (CB86; Ki = 1.6 nM) and a low (CB204; Ki = 117.7 nM) affinity TSPO ligands were investigated in H1299 lung cancer cell line exposed to CoCl₂. The lung cell line H1299 was chosen in the present study since they express TSPO and able to undergo programmed cell death. The examined cell death markers included: ATP synthase reversal, reactive oxygen species (ROS) generation, mitochondrial membrane potential (Δψm) depolarization, cellular toxicity, and cellular viability. Pretreatment of the cells with the low affinity ligand CB204 at a concentration of 100 µM suppressed significantly (p < 0.05 for all) CoCl₂-induced cellular cytotoxicity (100%), ATP synthase reversal (67%), ROS generation (82%), Δψm depolarization (100%), reduction in cellular density (97%), and also increased cell viability (85%). Furthermore, the low affinity TSPO ligand CB204, was harmless when given by itself at 100 µM. In contrast, the high affinity ligand (CB86) was significantly effective only in the prevention of CoCl₂–induced ROS generation (39%, p < 0.001), and showed significant cytotoxic effects when given alone at 100 µM, as reflected in alterations in ADP/ATP ratio, oxidative stress, mitochondrial membrane potential depolarization and cell death. It appears that similar to previous studies on brain-derived cells, the relatively low affinity for the TSPO target enhances the potency of TSPO ligands in the protection from hypoxic cell death. Moreover, the high affinity TSPO ligand CB86, but not the low affinity ligand CB204, was lethal to the lung cells at high concentration (100 µM). The low affinity TSPO ligand CB204 may be a candidate for the treatment of pulmonary diseases related to hypoxia, such as pulmonary ischemia and chronic obstructive pulmonary disease COPD. Full article

Probiotics, prebiotics, and synbiotics are potential mediators to maintaining healthy intestinal flora and have garnered an area of wide research in the past few years. The current study assesses the in vivo effects of probiotic (Lactobacillus plantarum MBTU-HK1), prebiotic (acacia gum) (either singly or in combination as a synbiotic on growth performance), biochemical, hematological, physiological, and immunological effects and their role in the reduction of procarcinogen enzyme activities in male Balb/c mice. The absence of treatment-related toxicity and a normal physiological range of biochemical and hematological parameters ensure their safe consumption. The synbiotic group was found to possess lowered cholesterol levels and enhanced protein and mineral content. The probiotic and synbiotic groups reinforced immunoglobulin levels and had a modulatory effect on phagocytosis. A lymphocyte proliferation pattern suggested the stimulatory effect of synbiotic combination on splenocyte viability and proliferation. Total antioxidant capability in the liver was determined by a 2,2-diphenyl-1-picrylhydrazyl assay and all the treatment groups were found to possess increased scavenging activity. Synbiotic and prebiotic treatment was observed to lead to reduced tumor necrosis factor α (TNF-α) levels. Bacterial procarcinogenic fecal enzyme activities were found to be decreased, proving their role in the prevention of colon cancer incidence. This study proves the potency and safety of oral administration of L. plantarum MBTU-HK1 and acacia gum either individually or in combination. Full article

Advanced nasopharyngeal carcinoma (NPC) has a poor prognosis because of the lack of an effective treatment. Here we explored the efficiency and the molecular mechanisms of combined treatment with triptolide and ionizing radiation for treating NPC. Human nasopharyngeal carcinoma (CNE) cells were treated with triptolide, ionizing radiation, or triptolide plus ionizing radiation in vitro. Tumor potency was examined in an in vivo CNE cell xenograft mouse model, which was treated as above. Our results demonstrated that triptolide caused a significant reduction in cell growth and colony number, and induced a marked apoptosis that was further enhanced with increasing doses of ionizing radiation. Combination treatment synergistically reduced tumor weight and volume without obvious toxicity. Western blot analysis in vitro and in vivo showed that triptolide induced apoptotic protein Bax expression and inhibited phosph-NF-κB p65, Bcl-2 and VEGF proteins without affecting other NF-κB related protein expression. In conclusion, our findings revealed that triptolide plus ionizing radiation had synergistic anti-tumor and anti-angiogenesis effects in NPC via down-regulating NF-κB p65 phosphorylation. The combination therapy may provide novel mechanism insights into inhibit NPC. Full article