The overexpression of the Epidermal Growth Factor Receptor (EGFR) is a pivotal factor in the progression of various cancers, making it a critical target for therapeutic intervention. This study employed molecular docking techniques to identify potential inhibitors against wild-type EGFR and its clinically relevant mutations, including the exon 19 deletion and T790M/L858R resistance mutations. Nine compounds, comprising five irreversible tyrosine kinase inhibitors (TKIs) and four small molecule natural compounds, were systematically screened using CB-dock2 computational tool. The drug-likeness and toxicity of these molecules were also examined based on their ADMET and Toxicity Prediction profiles. Among the tested compounds, Tetrandrine, Dauricine, and Olmutinib exhibited robust binding affinities across both wild-type and mutant EGFR configurations, highlighting their potential as effective inhibitors. These findings align with existing literature, reinforcing the importance of natural compounds and targeted inhibitors in combating EGFR-driven cancers. The integrated approach of combining molecular docking using CB-dock2, ADMET profiling, and Lipinski's rule of five provides a robust framework for preliminary drug candidate screening, potentially accelerating the development of more precise and effective EGFR-targeted therapies. The findings contribute to the growing body of research exploring alternative and more nuanced strategies for inhibiting EGFR-driven oncogenic mechanisms, highlighting the importance of computational methods in identifying novel molecular targets with improved specificity and reduced side effects.

Cancer remains a major global health challenge, and emerging research highlights the role of the gut microbiota in cancer development. This complex microbial community supports digestion, immunity, and even mental well-being, adapting to lifestyle factors like diet and exercise. One key function is the breakdown of tryptophan (Trp) into indole. Studies have linked these compounds to cancer, inflammatory conditions, and brain disorders. This review compiles evidence showing that indole derivatives produced by gut bacteria could serve as potential anticancer agents by targeting specific biochemical pathways. Mechanistically, these metabolites inhibit IDO1, lower kynurenine levels, decrease regulatory T cells, and increase CD8+ T cell responses. They also activate tumor-suppressive signaling pathways such as the aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR), and nuclear factor erythroid 2-related factor 2 (NRF2), while regulating reactive oxygen species (ROS). In addition, some indole derivatives trigger interleukin-12 (IL-12)-mediated T cell activation, leading to metabolic stress in cancer cells by downregulating UHRF1 and activating AMP-activated protein kinase (AMPK), thereby depleting ATP and causing cell death. Relevant literature was identified from PubMed, Google Scholar, and Scopus up to January 2026. Collectively, understanding this link could support development of personalized diets and microbiota-based cancer therapies.

p-cresyl sulfate (pCS) is a prominent uremic toxin and biomarker for the progression of chronic kidney disease (CKD). This article reports a highly selective and sensitive electrochemical sensor, designed for the early diagnosis of pCS. The sensor is designed with a screen-printed carbon electrode (SPCE) modified by multi-walled carbon nanotube (MWCNT), which improve electrical conductivity as well as helps in fast electron transfer. The detection of pCS was performed using molecularly imprinted polymer (MIP) synthesized with pyrrole as monomer to obtain polypyrrole (Ppy) polymer matrix, and a SnO2-rGO (Stannic oxide-reduced graphene oxide) nanocomposite was incorporated into the Ppy matrix during the process of polymerization. The resulted PpySnO2-rGO-MIP was immobilized onto the MWCNT-modified SPCE surface to produce highly selective binding cavities for pCS recognition. Structural analysis of the nanocomposite and MIP matrix was performed by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and selected area electron diffraction (SAED). Electrochemical characterization through cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) showed a superior sensor performance with sensitivity of 12.81 Omega (ng/mL)-1 cm-2, wide linear range of 50-3100 ng/mL, and low detection limit of 11.24 ng/mL. Density functional theory (DFT) calculations were performed with B3LYP/3-21 G method, which revealed a favorable interaction between pCS and pyrrole with a binding energy of -12.5 kcal/ mol and was supported by theoretical IR spectral shifts. Analysis on real sample by using pCS-spiked urine was also done, which indicated good recovery (102.2-103.2 %) and reproducibility (RSD: 1.5-3.8 %).

Indoxyl sulfate (IS) is a gut microbiota derived metabolite having various adverse implications in chronic kidney disease, cardiovascular disease, uremic syndrome. IS is also known as protein bound uremic toxin. Due to the serious issues caused by IS its timely quantification is important for the diagnosis and prevention of several diseases. Several traditional methods are available for detecting IS, including mass spectrometry and liquid chromatography. However, as these techniques are both time-consuming and costly our work represents the first demonstration of an electrochemical immunosensor for detecting IS using an anti-IS monoclonal antibody. The screen-printed carbon electrode (SPCE) was modified with a tertiary nanocomposite of chitosan-Au nanoparticles-CeO2 nanoparticles to provide abundant chemical groups through chitosan for the immobilization of antibodies and to deliver the synergistic effects of the Au-CeO2 nanocomposite such as improved surface area to volume ratio, electrical conductivity, and biocompatibility. The detection of IS using the fabricated label-free sensor was performed using the cyclic voltammetry technique. The fabricated sensor showed the sensitivity of 22.8 μA log10 (μM) cm-2 and LOD of 0.06 μM in the linear range of 1 nM to 1000 μM. The selectivity test was also performed on this immunosensor in the presence of various possible interference molecules found in human urine. The performance of the fabricated sensor was also assessed using a spiked urine sample, showing an acceptable recovery rate of 92.54-107.27%.

Intermittent fasting (IF) has emerged as a promising dietary approach with prospective advantages for clinical as well as non-clinical applications. Research indicates that IF enhances insulin sensitivity, facilitates weight reduction and stimulates cellular repair pathways, including autophagy. Physiological adaptations to fasting are reflected in favorable alterations in biomarkers and metabolic processes. This review examines the current evidence on IF by analyzing studies retrieved through schematic searches of the MEDLINE via PubMed database, Embase and ScienceDirect using specific keyword combinations. It focuses on commonly practiced regimens- Time-restricted eating (TRE) (16/8 method), Alternate-day fasting (ADF), the 5:2 intermittent energy-restriction diet and One meal a day (OMAD) approaches and explores their effects on cardiovascular function, metabolic regulation, cognitive performance and longevity. Various IF regimens including the TRE (16/8 method), ADF, the 5:2 diet and OMAD approaches are discussed in relation to their effects on cardiovascular health, cognitive function, metabolic regulation, aging and longevity. While most finding highlight significant health benefits, inconsistencies and methodological limitations are also reported. Mechanistically, IF orchestrates a coordinated metabolic response through modulation of key nutrient sensing pathway such as AMP activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR) and unc-51-like kinase 1 (ULK1). These cascades interact with Sirtuins (SIRT1/3), peroxisome proliferator activated receptor gamma coactivator-1α (PGC-1α) and the transcription factor EB (TFEB) to regulate autophagy, mitochondrial biogenesis, oxidative stress defense and cellular repair. Clinically, these molecular events underpin improvements in glycaemic control, lipid metabolism and inflammatory balance, supporting the therapeutic potential of IF for cardiometabolic disorders, neuroprotection and healthy aging.

Alveolar bone regeneration remains a significant challenge in dentistry and maxillofacial surgery due to the limited availability of autografts and the complexity of restoring the native bone microenvironment. In the present study, multifunctional bio-nanocomposite films composed of polyhydroxybutyrate (PHB), LAPONITE® nanoclay (LAP), and guar gum (GG) were fabricated by the solvent-casting technique and investigated as potential bioresorbable films for alveolar bone regeneration. Structural and physiological characteristics, characterized using FESEM, EDX, FTIR, XRD, and TGA confirmed the successful incorporation of LAPONITE® within the PHB/GG matrix and revealed significant modifications in the morphology, crystallinity, thermal behaviour, and surface characteristics of the films. The incorporation of LAPONITE® increased film thickness from 0.056 ± 0.005 mm in the control to 0.156 ± 0.007 mm in 10 wt% and significantly influenced the mechanical performance and porous microstructure of the bio-nanocomposites. Among the investigated formulations, the 5 wt% bio-nanocomposite film exhibited the most balanced combination of porous morphology, mechanical strength (123.90 ± 4.25 MPa), biomineralization behaviour, controlled degradation profile, antimicrobial activity, and cytocompatibility. In vitro biomineralization studies demonstrated the progressive formation of an apatite-like mineral layer following immersion in simulated body fluid (SBF), while degradation studies indicated a controlled mass-loss behaviour over 28 days. Antimicrobial evaluation against S. aureus demonstrated that the developed bio-nanocomposite films exhibited antimicrobial activity. Cytocompatibility assessment using MG-63 cells confirmed that all bio-nanocomposite films were non-toxic, with the 3-5 wt% formulations exhibiting the most favourable cellular response. Collectively, the developed PHB/LAPONITE®/guar gum bio-nanocomposite films demonstrated a favourable combination of structural integrity, mechanical performance, bioactivity, antimicrobial properties, and cytocompatibility, highlighting their potential for alveolar bone regeneration applications.

Acute liver failure (ALF) is characterized by rapid hepatocellular injury with profound metabolic and microbial dysregulation. Plasma metabolomics and metaproteomics performed in ALF patients (n = 270) identified a distinct non-survivor signature marked by elevated primary bile acids and tryptophan metabolites associated with inflammation, mitochondrial dysfunction, and cell death (p < 0.01, FDR < 0.01, FC > 1.5). ALF non-survivors also showed altered alpha/beta diversity (p < 0.05) with depletion of bacterial species linked to bile acid metabolism and redox homeostasis. Among cytotoxic metabolites, chenodeoxycholic acid (CDCA; logFC > 10) strongly predicted early mortality (HR > 1.7, p < 0.05). In an acetaminophen-induced ALF mouse model, Bacteroides intestinalis AM-1 (10⁹ CFU/ml), administered prophylactically and therapeutically, significantly reduced toxic metabolites, enhanced glutathione detoxification via L-histidine amino ligase and GSH synthetase (FC > 1.5, p < 0.05), activated FXR-FGF15 signaling, suppressed IL-1β/TLR4 pathways, reduced oxidative stress and caspase-3–mediated necroptosis (p < 0.05), and ameliorated liver injury by ~ 70%, supporting its therapeutic potential in ALF.

4-Ethyl phenyl sulfate (4-EPS), a gut microbiota-derived metabolite, is identified in ailments like chronic kidney disease (CKD) and numerous neurodegenerative conditions like autism spectrum disorders (ASD). This study is a novel attempt to comprehend the interaction of 4-ethyl phenyl sulfate (4-EPS) with human serum albumin (HSA). This interaction was examined using spectroscopic techniques like circular dichroism (CD), Fourier transform infrared (FTIR), UV-vis absorption, fluorescence spectroscopy, and molecular docking studies. The conformation investigation through FTIR and CD confirmed the alteration in the secondary structure of HSA due to the binding of 4-EPS. Fluorescence spectroscopy revealed the formation of a complex between HSA and 4-EPS upon interaction via static quenching. The spontaneity of the binding process was indicated by the negative ΔG value. Absorption spectroscopy demonstrated that in the presence of 4-EPS (2-48 μM), the absorbance of HSA progressively declined as a result of the formation of the 4-EPS-HSA complex. Contact angle measurements showed the involvement of hydrophobic interactions between HSA and 4-EPS. Molecular modeling was performed, followed by optimization using the DFT approach. Molecular docking study revealed moderate binding between the metabolite and HSA. It was further confirmed that hydrophobic interaction and hydrogen bonds were the main forces responsible for stabilizing the 4-EPS-HSA complex.

Cannabis sativa L., renowned for its versatility in pharmaceutical, textile, and cosmetic industries, is highly susceptible to several agronomic and environmental factors, particularly herbicides. These chemical agents, while commonly used for weed control, can adversely affect plant growth, physiology, and secondary metabolite production. Understanding the plant’s response to such external stressors is essential for optimizing its cultivation and ensuring the quality of its bioactive compounds. In our current work, we studied the impact of two herbicides- glyphosate and metribuzin on the morpho-physiological and biochemical characteristics of cannabis plants. The secondary metabolite production analysis was carried out using Gas Chromatography-Mass S pectrometry (GC-MS). Furthermore, in silico studies using molecular modelling and optimization via Density Functional Theory (DFT) were performed, followed by molecular docking. It was observed that both herbicides greatly impact overall plant productivity including primary and secondary metabolite production. Further, glyphosate treatment caused an increase in fatty acid synthesis while the contrary was observed in case of metribuzin. Also, herbicide stress leads to the synthesis of cannabidivarol and cannabidiol although they were absent in the untreated group. These findings provide crucial insights for optimizing agricultural practices in cannabis cultivation. Moreover, molecular simulation results showed that both metribuzin and glyphosate bind at the active pocket of Tetrahydrocannabinolic acid synthase (THCA synthase) and offer a mechanistic explanation for the observed variations in Δ9 -tetrahydocannabinol (THC) levels by suggesting that both herbicides inhibit THCA synthase activity, contributing to a deeper understanding of herbicide-plant interactions at the molecular level. Our findings indicate that herbicide stress impacts overall cannabis productivity and alters biosynthesis. The stress notably stimulates the production of cannabidivarol and cannabidiol. In addition, molecular docking studies revealed that metribuzin binds to the same active channel as Cannabigerolic acid (CBGA)- the THC precursor, while glyphosate binds at the entrance, thereby hindering THC production. This multifaceted approach guides sustainable farming strategies and has implications for manipulating cannabinoid profiles in pharmaceutical and other industrial applications.

Gut microbiota-derived metabolites have emerged as promising candidates in cancer therapeutics. Among these metabolites, 4-ethylphenyl sulfate (4-EPS), produced through dietary metabolism, is linked to chronic diseases but remains unexplored as a therapeutic agent for colorectal cancer (CRC) treatment. This study investigates the selective anticancer activity of 4-EPS using HCT-116 human colorectal adenocarcinoma cells and CCD 841 normal colon epithelial cells. Treatment with 4-EPS significantly reduced cell proliferation, viability, ATP levels, and colony-forming ability while increased apoptosis rate. Morphological changes included cell shrinkage, intracellular vesicle formation, and loss of membrane integrity. Mechanistically, 4-EPS upregulated Bax, downregulated Bcl2, and induced G2/M phase cell cycle arrest. In silico investigations revealed strong interactions with HDAC isoforms, suggesting epigenetic modulation. Markedly, 4-EPS treatment showed no deleterious effect on CCD 841 normal colon epithelial cells, which proved its selective anticancer role for colon cancer cells. These findings highlight 4-EPS as a promising therapeutic agent for treating CRC.

Continuous anthropogenic inputs have raised environmental concerns regarding non-degradable plastics derived from non-renewable petrochemicals, creating an urgent need for sustainable alternatives and driving a paradigm shift toward bioplastics. This review investigates the transformative role of the natural biopolymer xanthan gum as an eco-friendly additive in advancing biodegradable materials. Derived from Xanthomonas campestris, xanthan gum offers non-toxicity, biodegradability, and strong compatibility. The literature indicates that its negative charge enables interactions with positively charged molecules, enhancing composite properties such as mechanical strength. Although xanthan gum has limitations when used alone, it functions as an effective additive in packaging applications. The novelty of this work lies in exploring diverse techniques and formulations for integrating xanthan gum into bioplastic films and coatings, emphasizing its role in reinforcing biopolymer structures. As a sustainable alternative, xanthan gum-based composites preserve food quality and extend shelf life by providing protection against moisture, oxygen, UV radiation, and microbial contamination. Realizing its full potential requires optimized formulations to prevent structural disruptions and reduced stretchability at higher xanthan gum concentrations. Continued research, especially leveraging nanotechnology, is essential to amplify its advantages and address related challenges. This review highlights xanthan gum's pivotal contribution to bioplastic innovation, presenting a strong case for its broader adoption in the food packaging industry.

Prostate cancer (PCa) is the most commonly detected malignancy in men worldwide. PCa is a slow-growing cancer with the absence of symptoms at early stages. The pathogenesis has not been entirely understood including the key risk factors related to PCa development like diet and microbiota derived metabolites. Microbiota may influence the host's immunological responses, inflammatory responses, and metabolic pathways, which may be crucial for the development and metastasis. Similarly, short-chain fatty acids, methylamines, hippurate, bile acids, and other metabolites generated by microbiota may have potential roles in cancer inflammation and progression of cancer. Most studies have focused on the role of metabolites and their pathways involved in chronic inflammation, tumor initiation, proliferation, and progression. In summary, the review discusses the role of microbiota and microbial-derived metabolite-built strategies in inflammation and progression of the PCa.

Para-cresol sulfate (PCS), a gut metabolite and uremic toxin with a low molecular weight (188.02 g/mol), is a possible biomarker of interest due to its involvement in both health and sickness. We report, for the first time, the implication of PCS in diagnosis of chronic kidney disease (CKD) by using a highly sensitive detection platform based on streptavidin-poly HRP-AuNPs composite modified gold SPE. In this study, a broad panel of single-stranded DNA (ssDNA) aptamers targeting PCS were screened by a capture SELEX strategy, yielding candidates with huge affinity and specificity. Biolayer Interferometry (BLI) analysis confirmed that oligo 4 (a PCSspecific aptamer) exhibited the highest binding affinity towards target with K-d = 643 pM, in comparison to other screened aptamers whose K-d value ranged from 10.48 mM to 8.9 nM. With the obtained quantification and detection limit values as low as 169 pM and 50 pM, respectively, the produced apta-sensor demonstrated promising performance. The applicability of the aptasensor was evaluated using spiked human serum samples, and the low relative standard deviation (RSD) values indicated excellent reproducibility and minimal variation. Characterization of the functionalized electrode surface demonstrated excellent results in terms of repeatability, reproducibility, and stability, with RSD values of 2.67 %, 3.21 %, and 2.05 %, respectively. Circular dichroism (CD) spectroscopy supported the specific interaction between the PCS aptamer and its target, PCS. The results indicated a decrease in molecular ellipticity intensity upon complex formation, without any significant shift in characteristic wavelength indicating conformational stabilization rather than structural transition.

Human colon hosts a highly organized protective microbial ecosystem in the form of biofilms, increasingly recognized as key contributors to colorectal cancer (CRC) progression through microbial dysbiosis and complex host-microbiota interactions. In India, CRC ranks among the top ten cancers, with an age-standardized incidence rate of approximately 6.3 per 100,000 in males and 3.7 per 100,000 in females highlighting a higher risk in men, late-stage diagnosis, inadequate screening, and treatment limitations, particularly in urban populations. This study aims to explore the microbial composition of colonic biofilms from the Indian cohort of colorectal cancer patients from New Delhi, which is witnessing a rise in the incidence of CRC. Colorectal biopsies were taken from tumors (n = 15) and adjacent non-tumor tissues (n = 15) at the Gastrointestinal Department of AIIMS, New Delhi, India. Fluorescence in situ hybridization (FISH) was employed to determine the bacterial population in the biofilm. The workflow included microtomy, deparaffinization, tissue permeabilization, and hybridization with bacterial 16S rDNA probes, and the detected signals were visualized by confocal microscopy. The results showed quite different microbial patterns and tumor-associated biofilms were found to have an increased density of Escherichia coli, Klebsiella pneumoniae, and Bacteroides fragilis, while Fusobacterium nucleatum and E. coli (pks⁺) with a pks⁺ genomic island encoding the genotoxin colibactin were seen less often. These results confirm significant dysbiosis and the formation of invasive biofilms in CRC tissues. Understanding the composition of these biofilms may facilitate the development of targeted strategies to restore microbial balance and reduce CRC risk both in the Indian and global population. • Tumor-associated biofilms show distinct microbial dysbiosis in Indian CRC patients. • Enrichment of Escherichia coli, Klebsiella pneumoniae, and Bacteroides fragilis was observed at tumor site. • Insights into biofilm composition may aid to targeted interventions for CRC risk reduction.

Neurological disorders (NDs) represent a significant global health challenges, with neurodegeneration being a common pathological feature. Recent investigations indicate the involvement of gut microbiota-derived metabolites in these disorders, such as neuroinflammation, oxidative stress, and cognitive decline. The gut-brain axis, a communication network between the gut and the central nervous system (CNS), is influenced by microbial metabolites, which can cross the blood-brain barrier and impact brain function. Key metabolites such as trimethylamine N-oxide (TMAO), para-cresol sulfate (pCS), 4-ethylphenyl sulfate (4-EPS), and indoxyl sulfate (IS) have been linked with the progression of neurological disorders. TMAO disrupts blood-brain barrier integrity, promotes oxidative stress, and activates microglial cells, which lead to the apoptosis of neurons, resulting in neuroinflammation. This could also result in psychiatric changes and behavioral disorders. pCS produced from gut bacteria metabolizing dietary proteins is correlated with amplified oxidative stress, neuroinflammation, and cognitive impairments in disorders like Parkinson's disease and Alzheimer's disease. Similarly, elevated 4-EPS levels are linked to autism spectrum disorder, contributing to anxiety-like behavior and blood-brain barrier disruption. Understanding the mechanisms by which gut-derived metabolites affect neurological health could lead to novel therapeutic strategies that can target gut microbiota for the medication and treatment of neurological disorders. Dietary precursors and gut microbiota metabolites, modulated by probiotics, prebiotics, postbiotics, and synbiotics, play a critical role in maintaining microbiota homeostasis and influencing neurological health, needing sophisticated biosensors to enable real-time monitoring and early intervention in disorders linked to gut metabolite imbalances.

The Carcinogen benzo[a]pyran-7, 8 dihydrodiol 9, 10 epoxide(BaP-DNP) the active metabolite of benzo[a]pyrene has been postulated to induce carcinogenesis through formation of adduct with DNA and through alteration of critical pathways involved in signaling. Besides genotoxicity, BPDE has more recently been reported to alter the NF-κB, MAPK, and PI3K/Akt, that are involved in inflammation, cell survival and cell proliferation. From the above molecular docking analysis of BPDE binding to the potential proteins of these pathways, the mechanism of action of the compound is examined. The studies conducted on docking reveal moderate binding affinity of BPDE with NF-κB, that is, -6.11 kcal/mol, which points out its role in inflammation and oncogenic signaling. In addition, BPDE has more protein-binding affinities within the MAPK and PI3K/Akt pathway for CDK1 (-7.46 kcal/mol), LOX (-7.47 kcal/mol), and CDK6 (-6.84 kcal/mol). These indicate that influence of BPDE in tumour progression should not be only through the activation of NF-κB but would rather be supported by significant inputs of pathways that include PI3K/Akt and MAPK. This interaction would seem to favor cell survival, proliferation, and apoptosis resistance. Broader analysis of the data presented allows defining NF-κB as one of the key molecules contributing to BPDE-induced carcinogenesis; however, the data also point to the significant participation of the MAPK and PI3K/Akt pathways in this process. Future work should also more fully detail how these pathways interconnect and also evaluate the effectiveness of inhibiting NF-κB and related pathways in preventing BPDEs carcinogenic action. This study adds to understanding of molecular mechanisms and therapeutic targets of BPDE. Keywords: Carcinogenesis, Benzo[a]pyrene Diol Epoxide, Nuclear Factor Kappa B, Mitogen-Activated Protein Kinases, Phosphoinositide 3-Kinase /Akt ### Competing Interest Statement The authors have declared no competing interest.