Background/objective: The widespread use of pesticides in modern agriculture has raised increasing concern about their potential adverse effects on human health. Exposure to these compounds has been linked to multiple negative health outcomes. This systematic review aims to evaluate and synthesise the available scientific evidence on the effects of pesticide exposure on human health during agricultural production—with particular emphasis on alterations in gut microbiota and intestinal membrane permeability—by integrating results from experimental and observational studies conducted on animals and humans. Methods: This systematic review was conducted in accordance with PRISMA guidelines. A systematic literature search was carried out using the main databases Medline/PubMed, Embase and Web of Science, introducing the search algorithm “pesticides” AND “gut microbiota”, from which a total of seven systematic reviews that met our inclusion criteria were found and subsequently analysed. The quality assessment was based on the principles of evidence-based medicine. This systematic review was registered in the OSF. Results: The findings indicate that prenatal exposure to pesticides is linked to adverse outcomes in foetal development. Additionally, pesticide exposure affects metabolic, immune, and nervous system function due to alterations in gut microbiota composition and membrane permeability. Evidence from animal model studies complements human data by providing insight into the underlying biological mechanisms, such as oxidative stress, liver dysfunction, alterations in hormonal signalling and activation of the inflammatory response. Conclusions: Public health strategies should prioritise reducing pesticide exposure, strengthening environmental protection and supporting further research on gut microbiota modulation and intestinal membrane permeability. Such measures may contribute to the prevention and mitigation of pesticide-related health disorders. Limitations: Human data are insufficient to establish clear causal relationships. Moreover, substantial variability among pesticide types and the difficulty of distinguishing the effects of complex mixtures from those of individual compounds complicate interpretation of the findings.

Conventional nanoparticle manufacturing techniques remain costly, labor-intensive, and difficult to scale, while also being subject to batch-to-batch variability. These limitations hinder their clinical translation, particularly in first-in-human trials. Emerging transformative technologies such as microfluidics and three-dimensional (3D) printing offer opportunities to develop agile, continuous, and scalable manufacturing processes. This study aims to demonstrate the feasibility of continuous microfluidic production of nanoparticles using customizable 3D-printed chips, integrated with atomization technologies, to generate solid nano-enabled controlled release therapies. 3D-printed microfluidic chips were designed using computational fluid dynamics (CFD) to optimize flow characteristics. Nifedipine (NFD)-loaded nanoparticles were continuously manufactured with Eudragit L-100 and subsequently embedded into pullulan microparticles by spray-drying, yielding nano-in-microparticles (NIM). Particle size, encapsulation efficiency, solid-state properties,permeability, and release kinetics were assessed inex vivoFranz cell studies across porcine intestinal membranes. Continuous microfluidic processing produced NFD-loaded nanoparticles with 95% encapsulation efficiency. Spray-drying yielded spherical pullulan-based NIMs of ~ 10 µm, which, upon rehydration, released NFD nanoparticles of ~ 100 nm. The nanoparticles retained their amorphous state and displayed a three-fold increase in intestinal permeability compared to free drug, accompanied by a three-fold reduction in lag time. Release studies demonstrated reduced burst release and a sustained zero-order release profile over 24 h, favorable for blood pressure maintenance therapy. The integration of 3D-printed microfluidic chip design with continuous manufacturing and spray-drying enables scalable production of solid nano-enabled therapies. The NFD-loaded NIMs demonstrated enhanced permeability and controlled release, supporting the potential of this platform for the clinical translation of nanomedicines.

We evaluated whether serum biomarkers reflecting intestinal membrane integrity will serve as predictors for post-operative feeding intolerance (FI) in patients with congenital heart disease (CHD). We enrolled infants ≥ 35 weeks gestational age, aged 0-6 months, with complex CHD undergoing palliation surgery. After surgery, blood samples were obtained prior to the initiation of enteral feeds, at 7 and 14-days post feeding initiation, and at times of symptoms of FI and/or necrotizing enterocolitis (NEC). Plasma biomarkers of tight junction integrity (claudin-3), villus injury (I-FABP), and clinical outcomes were analyzed. Twenty-four infants were included in the analysis, and twelve of those had FI and/or symptoms of NEC. Patients in the FI group had higher peak claudin-3 than controls (p < 0.001). Claudin-3 was overall higher during 28 days after surgery in patients with FI. Pre-feeding I-FABP levels were higher for the FI group vs. control group (p = 0.006) but did not rise afterward. Higher cardiopulmonary bypass time and maximal lactate was associated with FI. Weight for length at discharge was significantly lower in patients with FI. We suggest that, when measured sequentially, plasma levels of I-FABP and claudin-3 may help to predict children with CHD at risk of feeding intolerance post cardiac surgery. If further validated in larger cohort, these biomarkers may aid in optimizing feeding protocols aimed at reducing sequelae such as NEC.

Propolis is a rich natural source of biologically active polyphenols; however, their therapeutic potential is often limited by poor oral bioaccessibility and bioavailability. This study reports the development and validation of a high-performance liquid chromatography-diode array detector (HPLC-DAD) method optimized for the quantification of major propolis polyphenols-caffeic acid (CA), pinocembrin (PC), chrysin (CR), caffeic acid phenethyl ester (CAPE), and galangin (GN) in 2-hydroxypropyl-β-cyclodextrin (HP-β-CD)-based complexes. A green complexation approach based on HP-β-CD and lyophilization was applied to continental propolis, yielding a water-soluble formulation suitable for oral administration. The isocratic HPLC-DAD method demonstrated linearity, sensitivity, and precision, suitable for reliable analysis of polyphneols in cyclodextrin-based matrices. Gastrointestinal behavior was evaluated using a simulated oral, gastric, and intestinal digestion model. PC and CAPE remained stable throughout digestion, whereas GN, CR, and CA showed higher sensitivity, with decreases of 43.1-71.6% compared to undigested samples. HP-β-CD complexation enhanced polyphenol solubility and improved gastrointestinal stability. Intestinal bioaccessibility, assessed by a centrifugation model, ranged from 77.2% (CR) to 124.9% (CA). However, the complexes did not permeate the artificial intestinal membrane, resulting in reduced dialyzable polyphenols, with CA being undetectable. These findings provide a validated analytical platform and mechanistic insight into the gastrointestinal behavior of cyclodextrin-complexed propolis polyphenols, supporting their application in oral functional formulations.

Synthesis, in vitro characterization and biopharmaceutical evaluation of a novel phosphate prodrug of sorafenib.

Bioaccessibility of Co-Occurring Mycotoxins in Brazilian Infant Foods at Regulatory Levels and Effect on the Intestinal Membrane Integrity

Polymeric micelles for oral drug delivery: progress and innovations in preclinical studies.

Tauopathies are neurodegenerative diseases characterized by accumulation of hyperphosphorylated tau protein (P-tau). The gut microbiota (GM) is symbiotic with the host and altered in neurodegenerative diseases. Amitriptyline (AMI) is a functional inhibitor of acid sphingomyelinase (ASM) which is abnormally highly expressed in brains of Alzheimer patients. Little data is known about the role of colonic ASM in management of tauopathy. Therefore, the aim of this study was to investigate the role of AMI on reversing gut dysbiosis, ceramide levels, colonic inflammation and intestinal barrier disruption in tauopathy through the bidirectional gut-brain axis. P301S transgenic mice were administered AMI for 35 days. Colonic ASM, ceramides, inflammation and membrane integrity were assessed besides fecal microbiome analysis and serum lipopolysaccharides to assess intestinal membrane disruption. Levels of hippocampal P-tau, protein phosphatase 2 A and neurogenesis were assessed along with cognitive behavior. AMI treatment significantly reduced colonic ASM, ceramide levels, increased abundance of Harryflintia, Dubosiella, and Parasutterella and decreased abundance of Lactobacillus, Lachnoclostridium, Oscillibacter, Oscillospiracea UCG-003, Colidextribacter, Roseburia, Butyricicoccus, and Sphingomondales. In contrast, P301S mice displayed an altered GM profile with enriched Firmicutes and Clostridia, and low proportions of Bacteroidota- a phylum associated with intestinal barrier protection-, and Ruminococcaceae. Also, AMI treatment decreased inflammation and restored colonic membrane integrity with subsequent decrease in serum lipopolysaccharides, P-tau in hippocampus and improvement in cognitive behaviour and neurogenesis. The current results indicate that AMI has neuroprotective effects against tauopathy through modulation of ASM activity, associated ceramide levels, GM composition, colonic inflammation and membrane integrity through bidirectional gut-brain axis.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1007/s11481-025-10270-x.

The structure of the mucous membrane of the small intestine in chickens of different sexes was studied. The Isa-Brown crossbred chickens were divided into two groups: males and females. In the birds’ small intestine, the volume of the entire mucosa and its individual structural parts (muscularis mucosae, crypts, villi) was investigated. The volume of connective tissue fibers located in the crypt area was also determined. The sex of the chickens has a pronounced influence on the indicators value. In males, 73.9 % of the mucosa volume is occupied by villi; 21.8 % by crypts; 4.3 % by the muscularis mucosae. In females, this ratio is 80.6 % – 15.7% – 3.7 %. Males have larger volumes of the muscularis mucosae and crypts. Females dominate only in terms of villi volume. The mucosa total volume has higher values in females, which exceed males in the duodenum by 1209.4 mm3 (P &lt; 0.05), in the jejunum by 2719.5 mm3 (P &lt; 0.05) and in the ileum by 424.2 mm3. In males, 70.4 % of the villi volume is occupied by the epithelial layer, and 29.6 % by the basal lamina. In females, this proportion is 74.8 % and 25.2 %. At the same time, in the entire small intestine, the largest values of the epithelium volume belong to females. They also have higher basal lamina volume of the villus in the jejunum and ileum. Connective tissue fibers support the structure and mechanical properties of the intestinal wall. Along the entire small intestine, the collagen fibers volume is greater in males, and elastic fibers in females. The males’ duodenum contains 12.3 % of the small intestine collagen fibers, the jejunum – 75.9 %, the ileum – 11.8 %. In females, the proportion of collagen fibers in this area is: 16.7 %, 73.4 % and 9.9 %, respectively. The proportion of elastic fibers in the males’ duodenum is 22.2 %, in the jejunum – 69.2 %, in the ileum – 8.6 %. In females, the distribution of elastic fibers along the intestinal wall is: 17.2 % – 73.7 % – 9.1 %. The presented sexual features of the small intestine mucosa morphology of chickens demonstrate its adaptive capabilities in accordance with the physiological state of the organism.

Synthesis, characterization, and anticancer evaluation of N-Heterocyclic entities: ADME profiling and In Silico predictions

Itraconazole loaded nanoemulsions: Hansen solubility & charge-driven permeation and GastroPlus based predicted In vivo performance.

Introduction: Diabetes mellitus is a metabolic disorder characterized by elevated blood glucose levels due to insufficient insulin production or insulin resistance. Although Metformin is a widely used anti-diabetic drug, its side effects necessitate the exploration of safer alternatives. This study investigates the anti-diabetic potential of Finger Millet (Eleusine coracana) by evaluating its absorption and permeability properties using in vitro models. Methods: The absorption and permeability of Finger Millet extract were compared with Metformin using the Franz cell diffusion and everted gut sac models. The extract’s absorption was measured at 239 nm, and its permeability through chicken ileum tissue was assessed to simulate intestinal absorption. Results: Finger Millet extract demonstrated superior absorption and permeability compared to Metformin. The extract showed a faster and more efficient diffusion across the intestinal membrane. Discussion: Its high content of phenolic compounds and flavonoids contributed to its anti-diabetic properties, likely by inhibiting carbohydrate-digesting enzymes (α-amylase, α-glucosidase). Conclusion: Finger Millet exhibits significant anti-diabetic potential, surpassing Metformin in terms of absorption and permeability. Its rich phytochemical composition offers a multi-targeted approach to diabetes management, making it a promising natural alternative to conventional drugs.

A chitin binding protein from the kuruma shrimp Marsupenaeus japonicus involved in WSSV infection.

Lysinuric protein intolerance (LPI) is an autosomal recessive disorder caused by variants in the SLC7A7 gene, leading to impaired transport of dibasic amino acids across intestinal and renal membranes. This results in postprandial hyperammonaemia due to deficiencies in lysine, arginine and ornithine, crucial substrates for the urea cycle. It commonly presents in infancy with recurrent vomiting, diarrhoea and encephalopathy. Diagnosis involves molecular genetic testing for the SLC7A7 gene variant. In this case, the rarity of the neuroimaging findings and the identification of an ultra-rare mutation contribute to the expanding clinical and genetic spectrum of LPI. Despite therapeutic advancements, the prognosis of LPI hinges on the progression of pulmonary and renal complications, underscoring the importance of comprehensive care and monitoring.

Deep eutectic solvents: A strategy for boosting alprazolam solubility and permeability in an intestinal membrane model

Celiac disease is a chronic autoimmune disease, the basis of its pathogenesis is damage of the mucous membrane of the small intestine by gluten. The prevalence of celiac disease is steadily rising and occurs in both children and adults. Clinical manifestations of celiac disease can be typical, i.e. the development of diarrhea, steatorrhea, malabsorption, and atypical ones. The aim: to deepen the knowledge of doctors about the polymorphism of clinical forms of celiac disease in children. Clinical case. The article highlights three cases of atypical course of celiac disease and gluten-sensitive disease. Various clinical forms of gluten intolerance in children are shown, which were manifested by recurrent alopecia, persistent seborrhea, pronounced abdominal syndrome after taking a gluten-containing product in combination with rapid physical activity. Conclusions. Іn addition to celiac disease, there are a number of that make their recognition complicated and delay their treatment. That is why timely clinical and laboratory diagnosis of gluten-sensitive diseases is important, and it allows us to recognize the disease on time, to prescribe treatment and thereby to optimize the prognosis. The research was carried out in accordance with the principles of the Declaration of Helsinki. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

BackgroundDangguiliuhuang Tang (DGLHT), a classic traditional Chinese medicine formula, has long been used to treat type 2 diabetes mellitus (T2DM). Nevertheless, its therapeutic efficacy, pharmacological foundation, and underlying mechanisms warrant further scientific exploration.MethodsUltra-high-performance liquid chromatography coupled with Thermo Vanquish UHPLC-Thermo Q Exactive HFX (UHPLC-QE-MS) was utilized to identify the chemical components of DGLHT. A potential therapeutic network for DGLHT in treating T2DM was constructed using network pharmacology. Untargeted metabolomics techniques were applied to reveal the differential effects of DGLHT on T2DM, and 16S rDNA amplification sequencing technology was used to investigate the differential metabolic regulation of gut microbiota in T2DM mice treated with DGLHT. Molecular biomedical experimental methods were combined to validate and analyze expression levels of the relevant proteins in the liver. A correlation analysis between the active ingredients of DGLHT and the differential gut microbiota was established.ResultsDGLHT improved glycemia, glucose tolerance, and liver injury in T2DM mice. A total of 38 major components were identified. Core targets included mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 3 (MAPK3), non-receptor tyrosine kinase (TNK), C-X-C motif chemokine ligand 8 (CXCL8), and serine/threonine kinase 1 (AKT1). DGLHT significantly altered the serum metabolic profile and gut microbiota composition in T2DM mice. These alterations affected inflammation-related Toll-like receptor signaling pathways, phosphorylation-associated ErbB signaling pathways, and functional substance metabolism related to bile secretion, cholesterol metabolism, biosynthesis of unsaturated fatty acids, protein digestion and absorption, cysteine and methionine metabolism, carbohydrate metabolism, intestinal membrane transport, and amino acid metabolism. DGLHT modulated protein expression in several key signaling pathways, including the toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB)/NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) pathway, phosphatidylinositide 3-kinase (PI3K)/protein kinase B (AKT)/glucose transporter type 4 (GLUT4) pathway, AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferators-activated receptor γ coactivator 1 alpha (PGC-1α) pathway, and heme oxygenase 1 (HO-1)/superoxide dismutase (SOD2)/catalase (CAT) pathway. The Candida genus and gamma-linolenic acid exhibited the strongest correlation.ConclusionDGLHT alleviates T2DM insulin resistance via multi-pathway regulation of inflammation, energy metabolism, and oxidative stress, mediated through metabolic and gut microbiota modulation.

Production of collagen-derived hydroxyproline (Hyp)-containing di- and tripeptides by brush border membrane enzymes and their absorption characteristics.

The particle drifting effect in vivo: impact of dose and animal species.

Nickel (Ni) is a significant environmental pollutant that poses a risk to human health due to its carcinogenic nature which involves DNA damage, oxidative stress, and disruption of cellular signaling pathways. These effects contribute to the development of lung, nasal, and sinonasal cancers, as well as damage to various tissues and organs. Nickel chloride (NiCl2), an inorganic divalent Ni compound, has been reported to induce oxidative stress in cellular systems by disrupting redox homeostasis. This study aimed to investigate the effect of a single acute oral dose of NiCl2 on the rat small intestine, especially on the antioxidant defence system and DNA integrity. Male Wistar rats were divided into five groups: one control (untreated) and four NiCl2-treated groups, each receiving single oral dose of NiCl2 at 45, 90, 135, and 180mg/kg body weight. NiCl2 treatment diminished the content of reduced glutathione and total sulfhydryl groups but increased lipid and protein oxidation and also hydrogen peroxide levels. The antioxidant power of the intestine was compromised due to inhibition of key antioxidant enzymes and decreased reduced glutathione levels which led to impaired free radical quenching and metal-reducing ability. Oral administration of NiCl2 inhibited the marker enzymes of intestinal brush border membrane. Enzymes of pathways of carbohydrate metabolism like glycolysis, gluconeogenesis, citric acid cycle, and hexose monophosphate shunt were also inhibited. The diphenylamine and comet assays showed significantly increased DNA fragmentation, while DNA-protein cross-linking in intestinal mucosa of NiCl2-administered animals was also elevated, when compared to the control group. Histopathology showed abnormal morphology of intestinal villi with marked lymphocytic infiltration in NiCl2-treated rats. This is likely due to increased ROS production and oxidative damage of cell components. All changes were seen in a NiCl2 dose-dependent manner. The observed intestinal damage could be due to significant impairment in the antioxidant defence system elicited by oxidative stress produced upon exposure to NiCl2 with more prominent changes at higher doses of the metal ion.