Cervical cancer is a malignant tumor that threatens women's health and radiotherapy represents a major therapeutic approach for its treatment; however, radioresistance frequently leads to treatment failure. The present study aimed to investigate whether loperamide (LOP), a µ‑opioid receptor agonist commonly used as an antidiarrheal agent, could enhance the radiosensitivity of cervical cancer cells by regulating ferroptosis. A Cell Counting Kit‑8 assay was used to evaluate the cytotoxicity of LOP in SiHa and HeLa cells, and EdU and colony formation assays were performed to assess cell proliferation. In addition, wound‑healing and Transwell assays were performed to detect cell migration. Flow cytometry was applied to measure cell apoptosis and intracellular reactive oxygen species (ROS) levels, and colorimetric assays were used to determine malondialdehyde (MDA) and glutathione (GSH) contents. The mRNA and protein expression levels of the ferroptosis‑related markers GSH peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) were analyzed using reverse transcription‑quantitative PCR and western blotting. The results showed that LOP significantly inhibited the viability of SiHa and HeLa cells, and exerted a synergistic effect with radiotherapy (combination index <1) to suppress cell proliferation and migration. Combined treatment with LOP and radiotherapy markedly increased apoptosis and ROS accumulation, elevated MDA levels and reduced GSH levels. Moreover, the combination treatment significantly downregulated the expression of GPX4 and SLC7A11. These findings indicated that LOP enhances the radiosensitivity of cervical cancer cells, with ferroptosis induction via inhibition of the GPX4/SLC7A11 axis as a contributing mechanism. Both apoptosis and ferroptosis were induced by the combination treatment, suggesting that the radiosensitizing effect may involve multiple cell death pathways. These observations provide a basis for further investigation into LOP as a potential radiosensitizing agent in cervical cancer.

Ceratonia siliqua L. (C. siliqua), commonly known as the carob tree, is an evergreen species of the Fabaceae family native to the Mediterranean basin and increasingly cultivated worldwide. Traditionally valued as animal feed and a natural sweetener, it has recently gained recognition as a multifunctional plant resource with nutritional, pharmaceutical, and industrial relevance. This review synthesizes current knowledge on the botany, phytochemistry, nutritional profile, bioactivity, and traditional uses of C. siliqua, and discusses its economic and industrial significance. Emphasis is placed on its rich content of polyphenols, flavonoids, dietary fiber, proteins, and essential minerals, which have been associated with antioxidant, antidiabetic, antidiarrheal, antimicrobial, and cardiometabolic-related activities. Beyond its nutritional potential, carob is increasingly used in food processing, functional foods, and pharmaceutical formulations, with locust bean gum as a key industrial derivative. Despite its long history, recent advances highlight new applications and the need for systematic quality control, valorization of genetic resources, and sustainable exploitation strategies. Overall, this review provides an integrative perspective that bridges traditional knowledge with modern scientific findings, aiming to guide future research and support broader utilization of carob as a natural bioresource in health, nutrition, and industry.

Abiotic humification via the Maillard reaction represents an indispensable geochemical process driving humic-like substance (HLS) formation and potential soil organic carbon (C) stabilization. Clay minerals act as critical modulators of this process, yet the differential mediating mechanisms of montmorillonite (Mont) and kaolinite (Kao)-two dominant soil clay minerals with distinct crystal structures-on glycine (Gly)-driven structural evolution of HLS remain poorly understood. Specifically, how Gly dosage couples with clay mineral types to modulate condensation reactions and structural differentiation of HLS has not been systematically clarified. In this study, a sterile abiotic reaction system was established with glucose and catechol as co-precursors, and five Gly concentration gradients (0, 0.03, 0.06, 0.12, and 0.24 mol/L) were set to investigate the regulatory effects of Gly on Maillard-derived HLS formation and structural evolution under Mont and Kao mediation. A combination of ultraviolet-visible spectroscopy, total organic carbon (TOC) analysis, elemental analysis, Fourier transform infrared (FTIR) spectroscopy, and partial least squares structural equation modeling (PLS-SEM) was applied to characterize HLS aromatic condensation, mineral-organic interactions, and abiotic humification pathways. Results showed that elevated Gly concentrations continuously increased the supernatant E4/E6 ratio and TOC content; this trend reflected enhanced adsorption of highly aromatic HLS fractions onto mineral surfaces, leaving simpler-structured components in the aqueous phase. The E4/E6 Amax relative increment reached 261.3% in Kao system versus 148.3% in Mont system, while Mont maintained more stable kinetic inflection x0 values with weaker fluctuation across Gly gradients. The optimal Gly concentration for humic-like acid (HLA) C (CHLA) accumulationwas 0.06 mol/L in both clay systems, where the maximum CHLA value of Kao group reached 3.00 g/kg, 69.5% higher than the 1.77 g/kg observed in Mont treatments. Over the full incubation period, the average CHLA/fulvic-like acid (FLA) C (CFLA) ratio of Kao system increased by 492.8%, merely 160.5% for Mont; Mont-derived HLA exhibited consistently higher H/C atomic ratios (1.28-1.94) than Kao HLA (0.94-1.83), verifying weaker aromatic condensation of Mont-produced humic fractions. Kao likely facilitated higher aromatic condensation, molecular maturity, and CHLA/CFLA ratio of HLS, whereas Mont restricted macromolecular polymerization through interlayer spatial confinement, producing HLA with higher H/C ratios and simpler molecular structures. FTIR spectra confirmed divergent responses of the two clay minerals to Gly gradients and strengthened mineral-organic coupling at the optimal 0.06 mol/L Gly dosage, with Kao displaying a wider fluctuation range (0.50-5.99) of polysaccharide C-O band intensity than Mont (0.91-1.01). PLS-SEM further verified that Gly addition directly drove early HLS formation, and mineral-organic coupling may serve as a key intermediate pathway related to HLS structural evolution and mineral-associated C retention. These findings likely reveal the structure-dependent regulatory patterns of typical soil clay minerals in abiotic humification under laboratory simulation, providing a preliminary mechanistic reference for optimizing precursor conditions to promote soil C stabilization.

Infectious diarrhoea is a serious threat to farm animals, especially newborns. This study aimed to investigate in vitro selective growth-inhibitory effects of 15 Indian ethnoveterinary plant ethanolic extracts, 5 antibiotic growth promoters, 5 antibiotics, 15 phytochemicals and their synthetic analogues against 12 diarrhoea-associated and 12 probiotic bacteria of veterinary concern. Minimum inhibitory concentrations (MIC≥ 80) of crude extracts and chemicals were determined by the broth microdilution method and log value of the ratio of selective indices (SI) were calculated. Among the tested agents, 8-hydroxyquinoline and chloroxine (SI = 1.3 and 0.7) showed selective antibacterial effects comparable to those of ciprofloxacin, doxycycline, and tetracycline (SI = 1.1, 0.8 and 0.9), respectively. The extracts of Embelia ribes fruit and Punica granatum epicarp (SI = 0.3 and 0.2, respectively) produced weak selectivity, inhibiting the growth of diarrhoea-causing strains at lower concentrations than beneficial microbiota. An ultra-high-performance liquid chromatography equipped with a mass spectrometer and a high-resolution accurate mass (UHPLC/MS-HRAM) analysis of E. ribes extract, that showed a certain degree of selectivity, highest amongst tested species, quantified abundant embelin (256.7-327.6 µg/mg of dry extract), which could be responsible for its antibacterial activity. To our knowledge, this is the first study investigating the growth-inhibitory effects of E. ribes and embelin toward gastrointestinal bacteria of veterinary significance. In conclusion, our study identifies potential growth-inhibitory activities of 8-hydroxyquinoline and E. ribes extract, supporting further investigation of their potential relevance for veterinary antidiarrhoeal research. However, further studies are necessary to explore their applications in farm animals.

Bacterial lysates (BL) are used as immunomodulators to prevent respiratory infections, though clinical evidence on efficacy remains inconsistent. Conventional oral administration may not provide optimal lung protection. This study explores inhalable microparticles containing BL associated to a locust bean gum (LBG) matrix as a strategy for pulmonary immunization against respiratory infections. LBG is a galactomannan showing mucoadhesive properties and potential to target antigen-presenting cells through mannose receptor interactions. BL-loaded LBG microparticles (LBG:BL = 10:0.2, w/w) were assessed regarding safety profile in respiratory cells (A549, Calu-3 and differentiated THP-1 cells) and in an airway 3D tissue model (MucilAir®). Assays demonstrated absence of toxicity (cell viability >70%) at physiological concentrations (38-76 μg/cm[2] or 125-250 μg/mL). Minimal generation of reactive oxygen species (ROS) was detected, and no significant alterations were observed on transepithelial electrical resistance (TEER), indicating satisfactory safety profile. In vivo pulmonary delivery of BL-loaded LBG microparticles more effectively induced mucosal IgA responses than controls. These findings support repurposing BL as immunomodulators for preventing respiratory infections through inhalable BL-loaded LBG microparticles, enhancing immune responses through antigen delivery to lung-resident immune cells and antigen presentation in bronchus-associated lymphoid tissue.

Trewia nudiflora L. (Euphorbiaceae) stem bark is traditionally used in Ayurvedic medicine for treating pain and gastrointestinal disorders, yet its bioactive constituents and underlying mechanisms remain unvalidated. This study aimed to isolate bioactive secondary metabolites from the methanol stem bark extract (MeOH-extract) of T. nudiflora and systematically evaluate its antidiarrheal, analgesic, thrombolytic, and membrane-stabilizing activities. Secondary metabolites were isolated via column chromatography and structurally characterized using [1]H and [13]C NMR. In vivo antidiarrheal (castor oil-induced), central (tail-immersion), and peripheral (acetic acid writhing) analgesic profiles were evaluated in Swiss-albino mice. In vitro thrombolytic and membrane-stabilizing assays were complemented by in silico molecular docking and ADMET profiling against five validated protein targets. Stigmasterol and (5α)-gitoxigenin 3-(α-L-rhamnopyranoside) were isolated as known constituents, providing chemotaxonomic confirmation, while the novelty lies in their integrated pharmacological and in silico characterization. The MeOH extract significantly reduced diarrheal feces by up to 60.46% (400 mg/kg), prolonged tail-immersion latency by 217.65%, and inhibited abdominal writhing by up to 65.39%. The extract showed 23.10% clot lysis and 79.14% hemolysis inhibition, while stigmasterol and gitoxigenin preferentially targeted μ-opioid (-5.856 kcal/mol) and EP2 receptors (-5.649 kcal/mol), respectively. ADMET profiling confirmed favorable oral absorption for stigmasterol (HIA = 96.4%, log BB = 0.80, LD50 = 890 mg/kg) and flagged gitoxigenin's narrow cardenolide safety margin (Toxicity Class II; LD50 = 41 mg/kg). These findings provide phytochemical and mechanistic support for the ethnomedicinal claims of T. nudiflora and identify both compounds as pharmacological leads warranting further investigation.

Background: Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease in which long-term maintenance of remission remains a major therapeutic challenge. Increasing evidence indicates that disruption of host-microbiome metabolic interactions, impaired production of short-chain fatty acids (SCFAs), defective epithelial energy metabolism, and intestinal barrier dysfunction contribute to disease relapse. These observations have generated interest in adjunctive metabolic strategies aimed at restoring luminal homeostasis rather than directly suppressing inflammation. Objective: This narrative review examines the biological rationale for combining pectin, a fermentable dietary fiber that promotes endogenous SCFA production, with kaolin, naturally occurring adsorbent clay, as adjunctive metabolic therapy for maintaining remission in UC. We summarize current mechanistic, experimental, and clinical evidence and discuss future translational research priorities. Evidence: Experimental studies demonstrate that pectin fermentation enhances the production of butyrate and other SCFAs, thereby improving epithelial energy metabolism, strengthening intestinal barrier integrity, and modulating mucosal immune responses. Kaolin possesses adsorptive and barrier-protective properties that may reduce luminal exposure to potentially harmful microbial products while improving stool consistency. Although direct clinical evidence supporting the combined use of pectin and kaolin in UC is currently lacking, indirect evidence derived from microbiome research, SCFA biology, dietary intervention studies, and experimental models provides a biologically plausible foundation for further investigation. Perspective: We propose that restoration of luminal metabolic homeostasis through complementary modulation of microbial fermentation and luminal environmental stabilization may represent a novel adjunctive approach for reducing relapse risk in selected patients with UC receiving conventional maintenance therapy. A conceptual framework for future randomized clinical trials incorporating clinical, endoscopic, microbiome, metabolomic, and biomarker outcomes is presented. Conclusions: Current evidence supports the biological plausibility of SCFA-directed metabolic interventions in UC but remains insufficient to justify routine clinical application of pectin-kaolin therapy. Well-designed randomized controlled trials are required to determine efficacy, safety, optimal patient selection, and mechanisms of action. By integrating advances in microbiome science, intestinal metabolism, and mucosal immunology, this review provides a translational framework for the development of inexpensive, microbiome-oriented adjunctive therapies for maintenance of remission in UC.

Several studies have supported Dr Gideon Koren’s 1993 landmark article, “Medications Which Can Kill a Toddler with One Tablet or Teaspoonful.” Although each study has its own merits, most focus solely on pediatric overdoses, and few provide an exhaustive reference list for real-time evaluation of ingestions in children and adults. The following xenobiotics warrant special attention because of their potential to cause serious outcomes, even after exposure to small volumes. This list does not imply that all pediatric exposures to these agents result in fatality, and the absence of a xenobiotic from this list does not indicate that it is necessarily safe. α1-Adrenergic agonists and imidazoline receptor agonists: Clonidine, guanfacine, naphazoline, oxymetazoline, tetrahydrozoline, xylazine (veterinary). Sulfonylureas: Chlorpropamide, glyburide, glipizide, glimepiride. Calcium channel blockers: Verapamil, diltiazem, nifedipine, amlodipine, nicardipine, nimodipine; β-Blockers: Metoprolol, labetalol, propranolol, sotalol. Tricyclic antidepressants: Imipramine, desipramine, amitriptyline, nortriptyline. Opioids: Codeine, hydrocodone, methadone, morphine, heroin. Antidiarrheals: Diphenoxylate plus atropine, loperamide. Salicylates and methyl salicylate: Oil of wintergreen, bismuth subsalicylate, mentholated balms, paramao or lawang root oil . Antipsychotics: Loxapine, thioridazine, chlorpromazine. Antimalarials: Chloroquine, hydroxychloroquine, quinine, primaquine. Antiarrhythmics: Quinidine, disopyramide, procainamide, flecainide, amiodarone. Camphor: A terpenoid used as an analgesic, antipruritic agent, and component of cooling gels, ointments, balms, mothballs, household fragrances, and essential oils. Oral camphor use occurs in some regions for religious ceremonies, traditional remedies, aphrodisiacs, or lactation suppression. Nonalkaloid toxic lignan: Podophyllin, podofilox. Unique plant toxins: Colchicine. Oral acetylcholinesterase inhibitors: Rivastigmine, donepezil, galantamine, carbamate pesticides. Methylxanthines: Theophylline, 1,3-dimethylxanthine, caffeine. Other opioids: Buprenorphine, fentanyl. Toxic alcohols: Methanol, ethylene glycol, diethylene glycol. Caustics and other household products: Acidic or alkaline household products, hydrofluoric acid, selenious acid, acetonitrile, methylene chloride. Accidental overdoses continue to occur regularly despite the implementation of various safety measures, including widespread public education, the use of childproof containers, and easy access to poison control centers. In the US, poison control centers receive more than 2.4 million calls annually, with more than 50% involving children younger than 6 years. Most pediatric accidental ingestions involve household cleaning products and analgesics, followed by cosmetics, foreign objects, and dietary supplements. Adult overdoses may be unintentional but often involve larger total doses or high-risk medications, including opioids and sedative-hypnotics. America's Poison Centers identify the 5 most common substance classes as analgesics, household cleaners, antidepressants, cosmetic or personal care items, and cardiovascular drugs. The number of ingestions involving cleaning products increased sharply during the COVID-19 pandemic but has since declined.

The poor water solubility of many drugs and drug candidates is a limiting factor to their bioavailability after oral administration. Although dissolution enhancing approaches, e.g. amorphous solid dispersions, are often used to make enabling formulations, these are usually associated with high development and manufacturing costs. This study focuses on the potential of using pharmaceutical excipients (binders) in simple tablet formulations to improve drug release and thus bioavailability. Loperamide hydrochloride, fenofibrate, compound c0 (a drug candidate) and carvedilol were chosen for this study as poorly water-soluble model compounds. Their solubility in the absence and presence of three polymeric binders, polyvinylpyrrolidone (PVP) K90, hydroxypropyl methylcellulose (HPMC) E4M and E15, and methylcellulose (MC) was tested in FaSSIF-V1 buffer and biorelevant media. Additionally, after wet granulation using PVP K90 or HPMC E15 as binders and tablet compression, the dissolution of the model compounds was tested in FaSSIF-V1 buffer and biorelevant media. Although solubilities and dissolution profiles of the model compounds were mostly improved by the binders, correlation between solubility in buffers and dissolution from the tablets in biorelevant FaSSIF-V1 was poor, indicating that dissolution experiments may be a better screening tool than solubility experiments. An important conclusion of these studies is that it is possible to increase the rate, and in some cases, the extent of dissolution of four poorly soluble drugs using wet granulation with polymeric binders, followed by tablet compression - a simple and cost-effective approach to improving drug performance.

Constipation is a common gastrointestinal disorder, which impairs the quality of life. This study investigated the ameliorative effects of 6'-sialyllactose (6'-SL) in a loperamide-induced murine model of constipation and associated depressive-like behaviors. Constipation was induced in mice by loperamide and subsequently treated by administering 6'-SL at doses of 100 or 300 mg per kg body weight for 14 days. The ameliorative effects of 6'-SL were evaluated through defecation-related parameters, histopathological and immunohistochemical analyses of colonic and hippocampal tissues, biochemical assays, behavioral tests, gut microbiota analysis, and short-chain fatty acid (SCFA) levels. The results showed that 6'-SL alleviated loperamide-induced constipation by improving defecation-related parameters, colonic histopathology, gastrointestinal neurotransmitter levels, and AQP3 and SCF/c-Kit levels. Moreover, 6'-SL ameliorated constipation-associated depressive-like behaviors and hippocampal alterations while modulating the gut microbiota composition and increasing the SCFA levels. Spearman's correlation analysis suggested that the alleviation of constipation and depressive-like behaviors may be associated with alterations in the gut microbiota and SCFA levels upon 6'-SL intervention. These results provide a theoretical and practical basis for developing functional foods and biomedical products based on 6'-SL.