Search Results (140)

Background: Dietitians play a critical role in preventing food–drug interactions (FDIs) and drug–nutrient interactions (DNIs); however, evidence regarding their knowledge, attitudes, and practices (KAP) in Saudi Arabia remains limited. Objective: The aim of this study was to assess dietitians’ KAP regarding FDIs and DNIs and examine their associations with socio-demographic and professional characteristics. Methods: A national cross-sectional study was conducted among 353 dietitians using a validated and modified questionnaire. Knowledge was assessed via 15 multiple-choice items (score range 0–15) and categorized as poor (0–5), moderate (6–10), or good (11–15). Attitudes were assessed using 8 Likert-scale statements (score range 8–40) and classified as negative (8–19), neutral (20–29), or positive (30–40). Practices were assessed via 6 frequency-scale items (score range 6–30) and categorized as poor (6–14), moderate (15–23), or good (24–30). Associations were analyzed using chi-square tests. Results: In total, 65.2% of participants demonstrated poor knowledge. Knowledge level was significantly associated with nationality (p = 0.011), educational qualification (p = 0.042), attendance at FDI/DNI training courses (p = 0.003), and inclusion of related topics during university education (p = 0.013). Higher knowledge levels were also associated with managing digestive diseases (p = 0.001), cardiovascular diseases (p = 0.020), and cancer (p = 0.031). Positive attitudes were reported by 77.6% of participants and were significantly associated with managing cardiovascular disease (p < 0.001) and obesity (p = 0.008). Good practices were observed in 36.3% of dietitians and were significantly associated with younger age (p = 0.024), more recent graduation (p = 0.006), fewer years of professional experience (p = 0.002), and managing obesity (p = 0.016). Knowledge was positively associated with practice (p < 0.001). Conclusions: Despite generally positive attitudes, substantial gaps in knowledge and practice regarding FDIs and DNIs exist among dietitians in Saudi Arabia. Strengthening academic curricula and continuing professional education is essential to enhance competency and improve patient safety. Full article

Cisplatin remains a widely used anticancer agent; however, its effectiveness can be influenced by systemic toxicity, resistance mechanisms, and interactions with exogenous compounds. Nicotinamide (vitamin B3), an NAD⁺ precursor and a commonly used dietary supplement, is involved in cellular metabolism, redox homeostasis, and DNA repair pathways, which may potentially modulate the cellular responses to Platinum-based agents. Here, we combine chemical synthesis, computational studies, spectroscopic analysis, and biological assays to investigate the molecular and biological aspects of Cisplatin–Nicotinamide interactions. A novel cis-[Pt(NH₃)₂NicotinamideCl]NO₃ complex was obtained and its structure analyzed. Density functional theory (DFT) calculations indicate a thermodynamically favorable coordination of Nicotinamide to the first hydrolysis product of Cisplatin (CisPt1) with binding energies comparable to those calculated for nucleobase coordination under the same theoretical conditions. In non-small cell lung cancer cell lines (A549 and PC-9), in vitro results suggest that Nicotinamide pre-treatment reduces Cisplatin cytotoxicity under specific experimental conditions, but the pre-formed complex does not exert anticancer effects. These data are consistent with a model in which Nicotinamide may interact with reactive Cisplatin species, potentially contributing to the reduced availability of reactive Platinum(II) species. This work provides mechanistic insight into potential drug–nutrient interactions involving Platinum-based chemotherapy and highlights the need for further investigation under clinically relevant conditions in the near future. Full article

Autophagy is a self-degradative homeostatic mechanism that plays an important role in tumor viability, metabolic reprogramming, and drug resistance. Circulating tumor DNA (ctDNA) is fragmented DNA that comes from dying tumor cells and leaks out into the blood stream. ctDNA can now be measured through blood tests and is a non-invasive way to identify cancer. ctDNA has shown promise for early detection of cancer, prognosis, and monitoring treatment response in real time. There is emerging mechanistic evidence suggesting a potential relationship between autophagy and ctDNA dynamics which has been discussed as a new autophagy–ctDNA axis. Autophagy can affect ctDNA levels by promoting or suppressing apoptosis and necrosis of tumor cells. When autophagy is cytoprotective, less DNA would be shed into the bloodstream. When autophagy is inhibited or defective, more DNA would be released because of increased genomic instability. Stressors found within the tumor microenvironment (TME) like hypoxia, oxidative stress, and nutrient depletion can also induce autophagy and indirectly affect ctDNA. Targeting autophagy therapeutically with drugs that induce or inhibit autophagy such as chloroquine (CQ) or mechanistic target of rapamycin (mTOR) inhibitors can affect ctDNA concentrations. Although emerging mechanistic evidence suggests a potential relationship between autophagy and ctDNA dynamics, direct clinical studies validating this interaction remain lacking. Therefore, this review presents the autophagy–ctDNA relationship as a hypothetical and exploratory model that warrants further mechanistic and translational investigation in cancer development, therapeutic resistance, and clinical applications. Full article

Glioblastoma multiforme (GBM) remains the most aggressive and therapeutically intractable primary brain tumor, with many patients experiencing rapid relapse despite maximal surgical resection followed by standard chemoradiation. This persistent failure reflects the convergence of profound tumor-intrinsic genetic heterogeneity and a highly dynamic, spatially structured, and immunosuppressive tumor microenvironment (TME). Together, these forces create strong selective pressures that fuel tumor evolution, intratumoral diversity, phenotype plasticity, diffuse invasion, and robust resistance to therapy. The TME of GBM is orchestrated through a complex interplay between diverse cellular constituents, including tumor-associated macrophages, reactive astrocytes, endothelial cells, pericytes, and GBM stem cells, and non-cellular components such as extracellular matrix remodeling, hypoxia, metabolic and nutrient gradients, and spatially patterned cytokine and chemokine signaling networks. Additionally, heterogeneity in blood–brain barrier (BBB) and blood–tumor barrier (BTB) complicates drug delivery and immune surveillance, reinforcing therapeutic resistance and regional tumor adaptation. Conventional two-dimensional cell cultures and animal models fail to sufficiently capture these multiscale, patient-specific interactions, limiting their translational predictive power. In this narrative review, we synthesize recent advances in GBM organoid technologies as physiologically relevant, three-dimensional platforms that more faithfully recapitulate TME for driving tumor evolution and treatment resistance. We compare complementary organoid strategies, including patient-derived GBM organoids that preserve native cytoarchitecture, cerebral organoid co-culture systems that reconstruct tumor–brain interactions, and advanced platforms incorporating immune and vascular features such as air–liquid interface cultures, microglia-enriched systems, and BBB/BTB-integrated models. Finally, we highlight emerging innovations such as spatial transcriptomics, organoid-on-a-chip systems, live imaging coupled with lineage tracing, genome engineering, and artificial intelligence integration that collectively position GBM organoids at the forefront of precision neuro-oncology, reproducing TME, enabling dynamic mapping of tumor evolution, and accelerating patient-specific therapeutic discovery. Full article

Background: Type 2 diabetes mellitus (T2DM) is commonly managed with complex pharmacotherapy combined with dietary modification, which increases the risk of clinically relevant drug–food interactions (DFIs). Despite their potential impact on treatment efficacy and safety, patient knowledge of DFIs—particularly in the context of modern therapies such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs)—remains insufficiently explored. Methods: This cross-sectional study assessed knowledge of DFIs among 103 adults with T2DM using a self-administered, expert-validated questionnaire. Data on sociodemographic characteristics, clinical variables, anti-diabetic therapy (including GLP-1 RAs), sources of education, and attendance at dietary consultations were collected. Knowledge scores were calculated based on correct responses and categorized into tertiles (low, moderate, high). Associations were analyzed using non-parametric tests. Multivariable logistic regression was performed to identify independent predictors of moderate-to-high DFI knowledge. Results: Substantial gaps in DFI knowledge were identified, particularly regarding interactions involving dietary fiber, dairy products, grapefruit juice, and nutrient deficiencies associated with long-term pharmacotherapy. Knowledge level was not significantly associated with age, educational attainment, diabetes duration, or GLP-1 RA use. Female sex was associated with higher knowledge in univariate analysis (p = 0.026); however, this association did not remain significant in the multivariable regression model. Attendance at at least one dietary consultation in the previous year was significantly associated with higher knowledge levels (p = 0.041) and remained an independent predictor in multivariable analysis (OR = 2.31; 95% CI: 1.04–5.15; p = 0.039). Most participants reported not receiving prior education on DFIs, while expressing a strong need for more frequent counseling. Conclusions: Patients with T2DM demonstrate insufficient knowledge of clinically relevant DFIs, including selected issues related to GLP-1 RA therapy. Attendance at structured dietary consultations was independently associated with higher levels of DFI knowledge; however, the directionality and causality of this relationship cannot be established. Given the cross-sectional design and the assessment of knowledge rather than behavioral or clinical outcomes, these findings should be interpreted as hypothesis-generating. Further longitudinal and interventional studies are required to determine whether improved DFI knowledge translates into meaningful changes in dietary behavior, treatment adherence, or metabolic outcomes. Full article

Inflammatory bowel diseases, comprising Crohn’s disease and ulcerative colitis, represent chronic inflammatory disorders with rising global incidence, underscoring the pivotal role of modifiable environmental factors in disease pathogenesis. Diet and intestinal microbiota have emerged as critical bidirectional therapeutic targets through complex interactions with host immune responses. Epidemiological evidence demonstrates that healthy and high fiber diets reduce disease risk, while ultra-processed foods and inflammatory dietary patterns increase susceptibility. Therapeutic nutritional interventions, including exclusive enteral nutrition, the Crohn’s Disease Exclusion Diet combined with partial enteral nutrition, and the Mediterranean diet can induce and maintain clinical remission while promoting favorable microbiome modifications characterized by the enrichment of butyrate-producing taxa such as Faecalibacterium prausnitzii and Roseburia species, alongside a reduction in pathogenic Proteobacteria. Micronutrient deficiencies affect up to 78% of patients through malabsorption, chronic blood losses, dietary restrictions, and drug–nutrient interactions. Nutritional status significantly impacts surgical outcomes, with preoperative malnutrition and sarcopenia associated with increased postoperative complications, and it reciprocally influences biologic therapy response. Integration of personalized, microbiome-informed dietary strategies as complementary components of comprehensive treatment plans represents a promising therapeutic frontier, requiring multidisciplinary collaboration, rigorous clinical trials with standardized microbiome analyses, and precision nutrition algorithms accounting for disease phenotype, baseline microbial composition, and individual patient characteristics to optimize outcomes and improve quality of life. Full article

Nanomaterials are widely used in biomedical research as drug and antibody carriers, and some nanomaterials have been shown to exhibit antimicrobial activity. Previously, silver nanoclusters (AgNCs) were predicted to interact with the bacterial TolC protein, which is involved in the development of multidrug resistance in pathogens. In this study, glutathione-coated AgNCs were synthesized and characterized. Their toxicological properties were studied in a microplate assay against five bacterial strains, both as single components and in mixtures with heavy metal salts and antibiotics. The resulting AgNCs had a diameter of 2.2 ± 0.5 nm, with excitation and emission maxima of λ = 490 nm and λ = 638 nm, respectively. No significant growth inhibition was observed at the concentrations used in resistance modulation assays (≤2.5 µg/mL Ag), except for transient effects at very high concentrations. A decrease in bacterial resistance to copper (II) and cadmium (II) cations and the antibiotics erythromycin and levofloxacin was observed upon the addition of AgNCs containing 2.5 μg/mL silver to the nutrient medium. A dose-dependent effect of AgNCs on bacterial resistance to toxicants was established. Thus, nanoclusters can be considered as inhibitors of bacterial resistance to heavy metals and antibiotics, which may be useful in studying bacterial adaptation mechanisms and developing technologies for overcoming multidrug resistance in bacteria. Full article

Background: Major Depressive Disorder (MDD) is more common in patients with Inflammatory Bowel Disease (IBD) than in the general population, suggesting a shared but unclear pathogenesis. Autophagy, a conserved intracellular cleaning process, maintains cellular health by removing debris and recycling nutrients. Given the limited research on autophagy in this comorbidity, this study investigated the role of autophagy-related genes in both disorders. Aim: This study aimed to identify shared autophagy-related mechanisms between IBD and MDD and to explore potential therapeutic strategies. Methods: We identified differentially expressed autophagy-related genes (DE-ARGs) in diseased versus normal tissues. Shared DE-ARGs between IBD and MDD were designated Co-DEGs. We analyzed correlations among Co-DEGs and their association with immune cell infiltration. Four machine-learning algorithms were used to pinpoint key biomarkers. Potential therapeutic agents were predicted and validated via molecular docking. Results: We identified 47 shared Co-DEGs. Among these, CASP1 emerged as a cross-disease shared susceptibility-associated gene (SSAG), consistently selected by all machine-learning models. Drug-gene interaction analysis and molecular docking identified compounds that could regulate CASP1. Single-cell analysis suggested CASP1 helps reshape the immune microenvironment in Crohn’s disease. Furthermore, Mendelian randomization identified WDR6 as a shared genetic risk factor for both conditions. Conclusions: Our findings illuminate autophagy-mediated mechanisms linking gut and brain disorders. The identification of CASP1 as a SSAG, along with candidate therapeutics, provides a foundation for future research and targeted treatments for IBD and MDD comorbidity. Full article

The high failure rate of anticancer drugs in clinical trials highlights the need for preclinical models that accurately reproduce the structural, biochemical, and mechanical complexity of human tumors. Conventional two-dimensional cultures and animal models often lack the physiological complexity required to predict clinical outcomes, driving the development of three-dimensional systems that better emulate the tumor microenvironment. Among these, microfluidic-based spheroid models have emerged as powerful tools for cancer research and drug screening. By integrating 3D spheroids with microfluidics, these platforms allow precise control of nutrient flow, oxygen gradients, shear stress, and interstitial pressure, while supporting co-culture with stromal, immune, and endothelial cells. Such systems enable the investigation of drug response, angiogenesis, metastasis, and immune interactions under dynamic and physiologically relevant conditions. This review summarizes recent advances in microfluidic spheroid models for cancer, covering both carcinomas and sarcomas, with an emphasis on device design, biomaterial integration, and translational validation. Key challenges remain, including technical complexity, scalability constraints, and the absence of standardized protocols. Overall, the merger of microfluidic technology with 3D spheroid culture provides a promising pathway toward predictive, ethical, and personalized preclinical testing, bridging the gap between in vitro modeling and clinical oncology. Full article

Garlic (Allium sativum L.) has served as a food source and medicinal agent for over thousands of years. Bioactive constituents, including allicin, diallyl sulfide/disulfide/trisulfide, ajoene, and S-allyl-cysteine, demonstrate antioxidant, anti-inflammatory, antithrombotic, antineoplastic, antimicrobial and neuroprotective properties. Convergent mechanistic evidence suggests the modulation of redox homeostasis, attenuation of pro-inflammatory signaling, regulation of platelet activation, and induction of apoptosis and cell-cycle arrest in tumor models. Computational studies, in conjunction with wet-lab data, offer molecular-level insights and guide candidate prioritization. Density functional theory elucidates radical-scavenging pathways and electronic descriptors that account for redox activity. Structure-based methods, including docking, molecular dynamics, and MM-GBSA, elucidate potential interactions between organosulfur scaffolds and enzymes or receptors pertinent to pharmacological effects. In silico ADME/Tox platforms predict generally favorable oral absorption for hydrophobic allyl sulfides, while polar derivatives exhibit more limited brain penetration. Emerging AI/ML pipelines combine network pharmacology with QSAR to focus on important targets and chemical types, while also spotting potential development. Formulation strategies, including nanoencapsulation and controlled-release systems, are utilized to stabilize labile thiosulfinates and modulate hydrogen-sulfide-releasing profiles, with potential applications in various disease conditions. Significant challenges encompass the standardization of preparations, variability in pharmacokinetics, heterogeneity in dose–response relationships, and interactions between drugs and nutrients or other drugs. The integration of mechanistic, computational, and formulation insights delineates a systematic approach to progress garlic-derived agents from diverse natural products to reproducible, mechanism-guided pharmaceuticals. Full article

Background/Objectives: Vitamin D deficiency is highly prevalent worldwide and is associated with multiple comorbidities and pharmacological treatments that may interfere with its metabolism. Evidence on the effect of supplementation across different drug user groups remains limited. Methods: A prospective study was conducted across community pharmacies over twelve months. Baseline socio-demographic, serum 25(OH)D concentration, quality of life (QoL), lifestyle habits, and medication use were collected. Participants received vitamin D supplementation for 12 months. Changes in vitamin D status and QoL were analyzed according to medication use. Logistic regression identified predictors of achieving adequate serum vitamin D levels (>30 ng/mL). Statistical significance was set at p < 0.05. Results: At baseline, 87.2% of 210 participants had insufficient or deficient vitamin D levels. After supplementation, mean serum vitamin D increased significantly from 21.3 ± 8.2 to 32.1 ± 12.6 ng/mL (p < 0.001), and QoL scores improved from 68.6 ± 18.7 to 77.8 ± 18.5 (p < 0.001). Dietary intake of vitamin D–rich foods and outdoor activity also increased. Supplementation improved vitamin D status among users of benzodiazepines, proton pump inhibitors, beta-blockers, statins, levothyroxine, metformin, and angiotensin-converting enzyme inhibitors, but not among corticosteroid, nonsteroidal anti-inflammatory drugs, or vitamin K antagonist. Multivariate analysis confirmed adherence as a strongest predictor of vitamin D adequacy (OR = 15.31, 95% CI = 2.90–80.75), while corticosteroid therapy, diabetes, and hypercholesterolemia were negatively associated. Conclusions: Vitamin D supplementation effectively corrected deficiency and improved QoL, but its efficacy varied according to comorbidities and medication use. Personalized supplementation strategies, emphasizing adherence and considering pharmacological profiles, may optimize outcomes. Further studies should explore mechanistic drug–nutrient interactions and long-term clinical implications. Full article

The intestine is a complex organ whose main functions are food digestion and nutrient absorption. It is therefore of great interest for pharmaceutical research as a preferred route for drug delivery. In vitro intestinal models are valuable tools for the preclinical evaluation of absorption, distribution, metabolism, and excretion of new therapeutic formulations; consequently, several attempts have been made to recreate the human intestine barrier in vitro. The models so far set up were aimed at mimicking specific intestinal features related to the molecules or processes under investigation. Artificial membranes are suitable to study passive absorption; systems based on 2D/3D cell cultures reproduce the transcellular pathway; organs-on-a-chip mimic the in vivo cellular and mechanical complexity, allowing the identification of the multiple factors involved in molecular interactions with the intestinal barrier; and intestine explants replicate in full the native organ under controlled conditions, thus providing the most comprehensive in vitro model. All these models have advantages and disadvantages but all have given important contribution to advance the knowledge on the interaction of drugs, toxins, and xenobiotic with the intestinal barrier. Full article

Dietary polyphenols are recognized as crucial modulators of gastrointestinal motility, holding therapeutic promise for conditions like irritable bowel syndrome, postoperative ileus, and functional dyspepsia. However, their reported effects are heterogeneous, ranging from spasmolytic to prokinetic. This review aims to clarify these inconsistencies by synthesizing experimental evidence on structure–activity relationships and underlying mechanisms. Relevant publications were identified in PubMed and Google Scholar using terms related to polyphenols and gastrointestinal motility. References were selected for relevance, and the narrative review integrates findings from in vitro, ex vivo, in vivo, and clinical studies. Across various experimental models, polyphenols function as multi-target modulators of gastrointestinal smooth muscle. The primary mechanisms identified involve the blockade of voltage-dependent L-type Ca²⁺ channels, activation of K⁺ channels (BK, K_ATP), and modulation of the NO/cGMP and cAMP/PKA pathways. Flavones and multiple flavonols consistently demonstrate spasmolytic activity via Ca²⁺ channel antagonism. In contrast, flavanones engage BK and K_ATP channels to induce membrane hyperpolarization. Complex extracts from plants like ginger and turmeric exhibit mixed pro- or antimotility effects, reflecting the diverse profiles of their constituent compounds. While robust ex vivo pharmacology and some in vivo and human data exist, a high degree of dataset heterogeneity and inconsistent reporting impedes direct translational efforts. Polyphenols are promising multi-mechanistic modulators of gastrointestinal motility with clear structure–activity patterns. To advance their clinical application, future research must focus on establishing standardized in vivo pharmacokinetics, conducting targeted structure–activity studies, employing bioassay-guided fractionation, and designing rigorous clinical trials. Full article

Gut microbial modulation through diet is central to human health and disease. Despite tremendous effort in understanding the impact of nutrients and drugs on the gut microbiota, and attempts to develop dietary strategies that facilitate gut-beneficial effects, several erroneous gut microbiota-associated concepts remain prevalent in popular belief. This article discusses widespread misconceptions about the gut microbiota, contrasting them with contemporary scientific facts. In this article, ten prevalent myths, including the obsolete 10:1 bacteria-to-human-cell ratio, the reductive categorization of microbes as ‘good’ or ‘bad’, and the discredited universal biomarker status of the Firmicutes/Bacteroidetes ratio in relation to metabolic diseases, have been debunked. Essential facts highlighting the context-dependency of the microbiome, considerable inter-individual heterogeneity, and dynamic reactivity to dietary changes are discussed. This questions the assumptions that increased diversity always signifies health, that probiotics are intrinsically safe, that fecal microbiota transplantation is a universal remedy, or that leaky gut syndrome constitutes a clearly defined diagnosis. It is highlighted that eubiosis and dysbiosis do not possess uniform criteria, and microbiome–drug interactions are extremely individualized. The gut microbiota operates as a dynamic, adaptive ecosystem, necessitating sophisticated, evidence-based methodologies for study and therapeutic application, transcending simplistic misconceptions in favor of tailored insights and therapies. Full article

Malaria persists as a paradigmatic model of co-evolutionary complexity, emerging from the dynamic interplay among a human host, Anopheles vectors, and Plasmodium falciparum parasites. In human populations, centuries of selective pressures have sculpted an intricate and heterogeneous immunogenetic landscape. Classical adaptations, such as hemoglobinopathies, are complemented by a diverse array of genetic polymorphisms that modulate innate and adaptive immune responses. These genetic traits, along with the acquisition of functional immunity following repeated exposures, mitigate disease severity but are continually challenged by the parasite’s highly evolved mechanisms of antigenic variation and immunomodulation. Such host adaptations underscore an evolutionary arms race that perpetually shapes the clinical and epidemiological outcomes. Intermediaries in malaria transmission have evolved robust responses to both natural and anthropogenic pressures. Their vector competence is governed by complex polygenic traits that affect physiological barriers and immune responses during parasite development. Recent studies reveal that these mosquitoes exhibit rapid behavioral and biochemical adaptations, including shifts in host-seeking behavior and the evolution of insecticide resistance. Mechanisms such as enhanced metabolic detoxification and target site insensitivity have emerged in response to the widespread use of insecticides, thereby eroding the efficacy of conventional interventions like insecticide-treated bed nets and indoor residual spraying. These adaptations not only sustain transmission dynamics in intervention saturated landscapes but also challenge current vector control paradigms, necessitating the development of innovative, integrated management strategies. At the molecular level, P. falciparum exemplifies evolutionary ingenuity through extensive genomic streamlining and metabolic reconfiguration. Its compact genome, a result of strategic gene loss and pruning, is optimized for an obligate parasitic lifestyle. The repurposing of the apicoplast for critical anabolic functions including fatty acid, isoprenoid, and haem biosynthesis highlights the parasite’s ability to exploit host derived nutrients efficiently. Moreover, the rapid accumulation of mutations, coupled with an elaborate repertoire for antigenic switching and epigenetic regulation, not only facilitates immune escape but also accelerates the emergence of antimalarial drug resistance. Advanced high throughput sequencing and functional genomics have begun to elucidate the metabolic epigenetic nexus that governs virulence gene expression and antigenic diversity in P. falciparum. By integrating insights from molecular biology, genomics, and evolutionary ecology, this study delineates the multifaceted co-adaptive dynamics that render malaria a recalcitrant global health threat. Our findings provide critical insights into the molecular arms race at the heart of host–pathogen vector interactions and underscore promising avenues for the development of next generation therapeutic and vector management strategies aimed at sustainable malaria elimination. Full article