The role of MNK1-mTORC1 pathway in modulating macrophage responses to Vibrio vulnificus infection.

Vibrio vulnificus (Vv) is known to cause life-threatening infections, particularly septicemia. These patients often exhibit elevated levels of pro-inflammatory cytokines. While it is established that mitogen-activated protein kinase (MAPK)-interacting kinase (MNK) contributes to the production of pro-inflammatory cytokines, the role of MNK in macrophages during Vv infection remains unclear. In this study, we investigate the impact of MNK on macrophages. We demonstrate that the inhibition of MNK in J774A.1 cells, when treated with lipopolysaccharide or Vv, resulted in decreased production of tumor necrosis factor alpha and interleukin-6, without affecting their transcription. Interestingly, treatment with MNK inhibitor CGP57380 led to enhanced phosphorylation of MNK1 but decreased phosphorylation of eIF4E. Moreover, MNK1 knockout cells exhibited an increased capacity for phagocytosis and clearance of Vv, with more acidic phagosomes than the parental cells. Notably, CGP57380 did not impact phagocytosis, bacterial clearance, or phagosome acidification in Vv-infected J774A.1 cells. Considering the reported association between MNK and mammalian target of rapamycin complex 1 (mTORC1) activation, we investigated the mTORC1 signaling in MNK1 knockout cells infected with Vv. Our results revealed that attenuation of the mTORC1 signaling in these cells and treatment with the mTORC1 inhibitor rapamycin significantly enhanced bacterial clearance in J774A.1 cells following Vv infection. In summary, our findings suggest that MNK promotes the Vv-induced cytokine production in J774A.1 cells without affecting their transcription levels. MNK1 appears to impair the phagocytosis, bacterial clearance, and phagosome acidification in Vv-infected J774A.1 cells through the MNK1-mTORC1 signaling pathway rather than the MNK1-eIF4E signaling pathway. Our findings highlight the importance of the MNK1-mTORC1 pathway in modulating macrophage responses to Vv infection. IMPORTANCE: Mitogen-activated protein kinase (MAPK)-interacting kinase (MNK) plays a role in promoting the production of tumor necrosis factor alpha and interleukin-6 in macrophages during Vibrio vulnificus (Vv) infection. Inhibition or knockout of MNK1 in J774A.1 cells resulted in reduced cytokine production without affecting their transcription levels. MNK1 also impairs phagocytosis, bacterial clearance, and phagosome acidification in Vv-infected cells through the MNK1-mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. The findings highlight the importance of the MNK1-mTORC1 pathway in modulating macrophage responses to Vv infection.

Drought response revealed by chromatin organization variation and transcriptional regulation in cotton.

BACKGROUND: Cotton is a major world cash crop and an important source of natural fiber, oil, and protein. Drought stress is becoming a restrictive factor affecting cotton production. To facilitate the development of drought-tolerant cotton varieties, it is necessary to study the molecular mechanism of drought stress response by exploring key drought-resistant genes and related regulatory factors. RESULTS: In this study, two cotton varieties, ZY007 (drought-sensitive) and ZY168 (drought-tolerant), showing obvious phenotypic differences under drought stress, were selected. A total of 25,898 drought-induced genes were identified, exhibiting significant enrichment in pathways related to plant stress responses. Under drought induction, At subgenome expression bias was observed at the whole-genome level, which may be due to stronger inhibition of Dt subgenome expression. A gene co-expression module that was significantly associated with drought resistance was identified. About 90% of topologically associating domain (TAD) boundaries were stable, and 6613 TAD variation events were identified between the two varieties under drought. We identified 92 genes in ZY007 and 98 in ZY168 related to chromatin 3D structural variation and induced by drought stress. These genes are closely linked to the cotton response to drought stress through canonical hormone-responsive pathways, modulation of kinase and phosphatase activities, facilitation of calcium ion transport, and other related molecular mechanisms. CONCLUSIONS: These results lay a foundation for elucidating the molecular mechanism of the cotton drought response and provide important regulatory locus and gene resources for the future molecular breeding of drought-resistant cotton varieties.

Microencapsulated essential oils alleviate diarrhea in weaned piglets by modulating the intestinal microbial barrier as well as not inducing antibiotic resistance: a field research.

Microencapsulated essential oils (MEO)have been used as antibiotic alternatives that can be applied to alleviate diarrhea in weaning piglet. We examined a large group of weaned piglets and incorporated essential oil containing thymol (2%), carvacrol (5%) and cinnamaldehyde (3%) in the feed of weaned piglets on an intensive production farm. The piglets were divided into four groups; Control (no additions) and chlortetracycline (Chl), essential oil (EO) and microencapsulated essential oil (MEO) were fed ad libitum over a 28-day trial period. We found MEO significantly reduced the incidence of diarrhea in the piglets that was also accompanied by increased average daily weight gains from days 14-28 (p < 0.05). MEO enhanced the antioxidant capacity in the piglets and serum total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-px) levels were significantly increased (p < 0.05). MEO also significantly reduced expression of genes related to ileal inflammation (IL-6, TNF-α and TGF-ß1) (p < 0.05) and significantly (p < 0.05) increased in sIgA antibody levels. MEO influenced the composition of the intestinal microbiome and reduced Bacteroidota (p < 0.05) and thus altered the Firmicutes/Bacteroidota ratio. However, none of the treatments produced significant changes in the most common tetracycline resistance genes (p > 0.05). Metagenomic analysis indicated that MEO impacted DNA expression, virulence factors, antioxidant activity and antimicrobial activity. Metabolomic analysis of the intestinal content also indicated that MEO impacted tyrosine metabolism and primary bile acid biosynthesis suggesting improved intestinal health and nutrient absorption. This study paves the way for further research into the development and optimization of MEO-based interventions aimed at improving piglet health and performance while also providing a reference for reducing reliance on antibiotics in animal agriculture.

Biosynthesis of Scopoletin in Sweet Potato Confers Resistance against Fusarium oxysporum.

Fusarium wilt is a severe fungal disease caused by Fusarium oxysporum in sweet potato. We conducted transcriptome analysis to explore the resistance mechanism of sweet potato against F. oxysporum. Our findings highlighted the role of scopoletin, a hydroxycoumarin, in enhancing resistance. In vitro experiments confirmed that scopoletin and umbelliferone had inhibitory effects on the F. oxysporum growth. We identified hydroxycoumarin synthase genes IbF6'H2 and IbCOSY that are responsible for scopoletin production in sweet potatoes. The co-overexpression of IbF6'H2 and IbCOSY in tobacco plants produced the highest scopoletin levels and disease resistance. This study provides insights into the molecular basis of sweet potato defense against Fusarium wilt and identifies valuable genes for breeding wilt-resistant cultivars.

Preparation of meaty flavor additive from soybean meal through the Maillard reaction.

Meaty flavor additive was prepared from soybean meal hydrolysate and xylose in the method of Maillard reaction. Under the conditions of reaction temperature 120 ℃, time 120 min and cysteine addition 10%, the Maillard products had strong flavor of meat. The content of free amino acids was 4.941 µ mol/mL in the products. There were 50 volatile flavor substances in Maillard reaction products according to GC-MS analysis. 4 mercaptans, 4 sulfur substituted furans, 3 thiophenes, 7 furans, 6 pyrazine, 3 pyrrole, 1 pyrimidine, 7 aldehydes, 4 ketones, 7 esters, 2 alcohols and 2 acids were included. The Maillard reaction products also have strong antioxidant activity. The scavenging ability of FRAP, DPPH radical, hydroxyl radical and ABTS+ radical was 1.82%, 69.8%, 68.7% and 71.6% respectively. The products of Mailard reaction have potential to be used in food additives.

Tcbf: a novel user-friendly tool for pan-3D genome analysis of topologically associating domain in eukaryotic organisms.

SUMMARY: TAD boundaries are essential for organizing the chromatin spatial structure and regulating gene expression in eukaryotes. However, for large-scale pan-3D genome research, identifying conserved and specific TAD boundaries across different species or individuals is computationally challenging. Here, we present Tcbf, a rapid and powerful Python/R tool that integrates gene synteny blocks and homologous sequences to automatically detect conserved and specific TAD boundaries among multiple species, which can efficiently analyze huge genome datasets, greatly reduce the computational burden and enable pan-3D genome research. AVAILABILITY AND IMPLEMENTATION: Tcbf is implemented by Python/R and is available at https://github.com/TcbfGroup/Tcbf under the MIT license.

Florfenicol sustained-release granules: an in vitro-in vivo correlation study in pigs.

The objective of this study was to synthesize and characterize pharmaceutical characteristics of florfenicol sustained-release granules (FSRGs) in vitro and in vivo. FSRGs were synthesized using monostearate, polyethylene glycol 4000 and starch. In vitro dissolution profiles were studied using the rotating basket method in pH 1.2 HCl solution and pH 4.3 acetate buffer. Twenty-four male healthy Landrace×Yorkshire pigs were equally divided into three groups and administered a 20 mg/kg i.v bolus of florfenicol solution and dosed orally with FSRGs in the fasting and fed states. The Higuchi model was the best fit for the drug release profile in pH 1.2 and pH 4.3 media, and the mechanism of drug dissolution was governed by both diffusion and dissolution. We established a level A in vitro - in vivo correlation for FSRGs and the in vivo profile of the FSRGs can be estimated by the in vitro drug release.

Shikimic Acid Regulates the NF-κB/MAPK Signaling Pathway and Gut Microbiota to Ameliorate DSS-Induced Ulcerative Colitis.

Shikimic acid (SA) is a compound extracted from the plant anise and has anti-inflammatory effects. However, any impact on intestinal inflammation or mechanisms involved has not been investigated. The present study used a dextran sulfate sodium (DSS)-induced mouse colitis model to investigate the effects of SA on intestinal inflammation. Intragastric administration of SA slowed DSS-induced weight loss, reduced disease activity index (DAI) score, enhanced the intestinal barrier, reduced the destruction of the colonic structure, inhibited the phosphorylation of key proteins in MAPK and NF-κB signaling pathways, inhibited the expression of inflammatory factors TNF-α, IL-1ß, and MPO (P < 0.05), decreased IFN-γ expression (P < 0.05), and increased immunoglobulin IgG content (P < 0.05). After 50 mg/kg SA treatment, the content of Bacteroidetes increased and Proteobacteria decreased in the cecal feces of mice with colitis (P < 0.05) and the richness of gut species increased. In conclusion, SA could improve intestinal inflammation and enhance intestinal immunity, indicating its suitability as a therapeutic candidate.

Two kinds of lateral flow immunoassays based on multifunctional magnetic prussian blue nanoenzyme and colloidal gold for the detection of 38 ß-agonists in swine urine and pork.

Herein, novel multifunctional magnetic prussian blue nanoenzymes (MPBNs) and colloidal gold (CG) were synthesized and used to develop two kinds of lateral flow immunoassays (LFIAs) for the detection of 38 ß-agonists. Since MPBNs has a unique three-in-one function of colorimetric magnetic catalytic activities, the signal intensity and coupling ratio are 2 and 8-fold higher than that of the CG. The cut-off values of the CG-LFIA and MPBNs-LFIA for swine urine and pork are 5/5 and 0.3/0.5 µg/kg, the limits of detection are 0.19/0.29 and 0.02/0.03 µg/kg, respectively. The sensitivity of MPBNs-LFIA is 10-fold higher than that of CG-LFIA, and up to 200-fold higher than that of the reported LFIAs. The recoveries of the LFIAs are 80.0%-116.7%, with coefficients of variation of 1.4%-14.3%. Our study proved that the MPBNs have more advantages than CG, and can offer a promising signal label for ultrasensitive immunoassay techniques.

Hemp seed protein and chlorogenic acid complex: Effect of ultrasound modification on its structure and functional properties.

In this study, the effects of ultrasound and chlorogenic acid (CA) on the structural and functional properties of hemp seed protein (HSP) was investigated. Compared with natural HSP, the UV-vis spectra intensity of ultrasound-treated HSP (UHSP) and UHSP-CA increased, the fluorescence spectra intensity decreased with a red shift in the maximum intensity peak. The results showed that ultrasound modification and complexation with CA unfolded the structure of HSP exposing its internal groups. Fluorescence quenching analysis showed that the best binding between UHSP and CA (binding constant 2.94 × 102 L/mol) was achieved at 450 W for 15 min of ultrasound treatment. In addition, the same ultrasound conditions minimized the particle size and surface roughness of UHSP and UHSP-CA. The solubility of UHSP and UHSP-CA increased by 23.3 and 38.7 %, the emulsifying activity index increased by 16.9 and 16.2 %, and the emulsion stability index increased by 20.9 and 20.8 %, respectively. These results indicated that appropriate ultrasound treatment and complexation with CA can significantly modify the structural and functional properties of HSP, improving its application value in the food field.

Dietary supplementation with a microencapsulated complex of thymol, carvacrol, and cinnamaldehyde improves intestinal barrier function in weaning piglets.

BACKGROUND: The authors previously prepared a microencapsulated complex of thymol, carvacrol, and cinnamaldehyde (MEEO). This study aimed to evaluate the effect of MEEO on the intestinal mucosal barrier and homeostasis in weaning piglets. A comparison of the effect of MEEO versus chlortetracycline (CTC) was performed in this study. RESULTS: Piglets were divided into three groups - control (Con), MEEO, and CTC groups - and raised for 28 days. The results showed that MEEO significantly elevated the ratio of the villus height and the crypt depth in the jejunum and decreased the crypt depth in the ileum compared with the other groups (P < 0.05); it also upregulated the messenger ribonucleic acid (mRNA) expression of tight junction protein in the small intestine. Compared with the Con group, MEEO increased the concentration of secretory immunoglobulin A (sIgA), cathelicidin antimicrobial peptides (CAMP), and interleukin 10 (IL-10), while decreasing the interleukin 1 beta (IL-1ß) concentration in both jejunal and ileal mucosa (P < 0.05). The mRNA expression of jejunal mucosal MUC1 and ileal mucosal MUC2 was increased in the MEEO group compared with the other groups (P < 0.05). Intestinal microbial analysis showed that dietary treatment had little impact on the ileal microbial structure. A significant rise in the genus Lactobacillus was, however, found in the MEEO group. There is a positive correlation between the Lactobacillus and sIgA, and between the Lactobacillus and CAMP, indicating that an improvement in the mucosal barrier function by the addition of MEEO may be associated with the proliferation of Lactobacillus. CONCLUSION: Dietary supplementation with MEEO improves intestinal barrier function in weaning piglets, the effect of which was superior to CTC. © 2022 Society of Chemical Industry.

Genomic innovation and regulatory rewiring during evolution of the cotton genus Gossypium.

Phenotypic diversity and evolutionary innovation ultimately trace to variation in genomic sequence and rewiring of regulatory networks. Here, we constructed a pan-genome of the Gossypium genus using ten representative diploid genomes. We document the genomic evolutionary history and the impact of lineage-specific transposon amplification on differential genome composition. The pan-3D genome reveals evolutionary connections between transposon-driven genome size variation and both higher-order chromatin structure reorganization and the rewiring of chromatin interactome. We linked changes in chromatin structures to phenotypic differences in cotton fiber and identified regulatory variations that decode the genetic basis of fiber length, the latter enabled by sequencing 1,005 transcriptomes during fiber development. We showcase how pan-genomic, pan-3D genomic and genetic regulatory data serve as a resource for delineating the evolutionary basis of spinnable cotton fiber. Our work provides insights into the evolution of genome organization and regulation and will inform cotton improvement by enabling regulome-based approaches.

Pharmacokinetics, bioavailability, and excretion of ponazuril in piglets.

Ponazuril is a triazine anticoccidial drug which is the main metabolite of toltrazuril in animals, it has excellent activity against many protozoa, including Cystoisospora suis, and has broad application prospects in the control of swine coccidiosis. To evaluate the pharmacokinetic and excretion characteristics of ponazuril, 12 healthy piglets aged 10-14 days were divided into 2 groups for pharmacokinetic studies, which were given 20 mg/kg body weight ponazuril orally and intravenously, respectively. And 6 other piglets were housed individually in metabolic cages and given the same oral dose of ponazuril. After administration, the concentration of ponazuril in plasma, fecal, and urine samples collected was determined using high-performance liquid chromatography (HPLC). The plasma concentration profiles of ponazuril obtained after intravenous and oral administration were analyzed simultaneously by the nonlinear mixed-effects (NLME) model. Following the results, the pharmacokinetics of ponazuril exhibited a Michaelis-Menten elimination with Michaelis-Menten constant Km and maximum metabolic rate Vm of 10.8 µg/mL and 0.083 mg/kg/h. The apparent volume of distribution was calculated to be 735 mL/kg, and the final estimated oral bioavailability was 81%. Besides, cumulatively 86.42 ± 2.96% of ponazuril was recovered from feces and 0.31% ± 0.08% from urine during 0-1,020 h after oral administration. These findings indicated a good oral absorption of ponazuril in piglets with nonlinear disposition and slow excretion largely via feces, implying sustained drug concentration in vivo and long-lasting anticoccidial effects.

Preoperative contrast-enhanced computed tomography-based radiomics model for overall survival prediction in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy with a rising incidence worldwide. The prognosis of HCC patients after radical resection remains poor. Radiomics is a novel machine learning method that extracts quantitative features from medical images and provides predictive information of cancer, which can assist with cancer diagnosis, therapeutic decision-making and prognosis improvement. AIM: To develop and validate a contrast-enhanced computed tomography-based radiomics model for predicting the overall survival (OS) of HCC patients after radical hepatectomy. METHODS: A total of 150 HCC patients were randomly divided into a training cohort (n = 107) and a validation cohort (n = 43). Radiomics features were extracted from the entire tumour lesion. The least absolute shrinkage and selection operator algorithm was applied for the selection of radiomics features and the construction of the radiomics signature. Univariate and multivariate Cox regression analyses were used to identify the independent prognostic factors and develop the predictive nomogram, incorporating clinicopathological characteristics and the radiomics signature. The accuracy of the nomogram was assessed with the concordance index, receiver operating characteristic (ROC) curve and calibration curve. The clinical utility was evaluated by decision curve analysis (DCA). Kaplan-Meier methodology was used to compare the survival between the low- and high-risk subgroups. RESULTS: In total, seven radiomics features were selected to construct the radiomics signature. According to the results of univariate and multivariate Cox regression analyses, alpha-fetoprotein (AFP), neutrophil-to-lymphocyte ratio (NLR) and radiomics signature were included to build the nomogram. The C-indices of the nomogram in the training and validation cohorts were 0.736 and 0.774, respectively. ROC curve analysis for predicting 1-, 3-, and 5-year OS confirmed satisfactory accuracy [training cohort, area under the curve (AUC) = 0.850, 0.791 and 0.823, respectively; validation cohort, AUC = 0.905, 0.884 and 0.911, respectively]. The calibration curve analysis indicated a good agreement between the nomogram-prediction and actual survival. DCA curves suggested that the nomogram had more benefit than traditional staging system models. Kaplan-Meier survival analysis indicated that patients in the low-risk group had longer OS and disease-free survival (all P < 0.0001). CONCLUSION: The nomogram containing the radiomics signature, NLR and AFP is a reliable tool for predicting the OS of HCC patients.

A rechargeable molecular solar thermal system below 0 °C.

An optimal temperature is crucial for a broad range of applications, from chemical transformations, electronics, and human comfort, to energy production and our whole planet. Photochemical molecular thermal energy storage systems coupled with phase change behavior (MOST-PCMs) offer unique opportunities to capture energy and regulate temperature. Here, we demonstrate how a series of visible-light-responsive azopyrazoles couple MOST and PCMs to provide energy capture and release below 0 °C. The system is charged by blue light at -1 °C, and discharges energy in the form of heat under green light irradiation. High energy density (0.25 MJ kg-1) is realized through co-harvesting visible-light energy and thermal energy from the environment through phase transitions. Coatings on glass with photo-controlled transparency are prepared as a demonstration of thermal regulation. The temperature difference between the coatings and the ice cold surroundings is up to 22.7 °C during the discharging process. This study illustrates molecular design principles that pave the way for MOST-PCMs that can store natural sunlight energy and ambient heat over a wide temperature range.

Poloxamer 407/188 Binary Thermosensitive Gel as a Moxidectin Delivery System: In Vitro Release and In Vivo Evaluation.

Moxidectin (MXD) is an antiparasitic drug used extensively in veterinary clinics. In this study, to develop a new formulation of MXD, a thermosensitive gel of MXD (MXD-TG) was prepared based on poloxamer 407/188. Furthermore, the gelation temperature, the stability, in vitro release kinetics and in vivo pharmacokinetics of MXD-TG were evaluated. The results showed that the gelation temperature was approximately 27 °C. MXD-TG was physically stable and can be released continuously for more than 96 h in vitro. The Korsmeyer−Peppas model provided the best fit to the release kinetics, and the release mechanism followed a diffusive erosion style. MXD-TG was released persistently for over 70 days in sheep. Part of pharmacokinetic parameters had a difference in female and male sheep (p < 0.05). It was concluded that MXD-TG had a good stability, and its release followed the characteristics of a diffusive erosion style in vitro and a sustained release pattern in vivo.

Controlled Synthesis of a Two-Dimensional Non-van der Waals Ferromagnet toward a Magnetic Moiré Superlattice.

Two-dimensional (2D) magnetic materials provide an ideal platform for spintronics, magnetoelectrics, and numerous intriguing physical phenomena in 2D limits. Moiré superlattices based on 2D magnets offer an avenue for controlling the spin degree of freedom and engineering magnetic properties. However, the synthesis of high-quality, large-grain, and stable 2D magnets, much less obtaining a magnetic moiré superlattice, is still challenging. We synthesize 2D ferromagnets (trigonal Cr5Te8) with controlled thickness and robust stability through chemical vapor deposition. Single-unit-cell-thick flakes with lateral sizes of tens of micrometers are obtained. We observe the layer-by-layer growth mode for the crystal formation in non-van der Waals Cr5Te8. The robust anomalous Hall signal confirms that Cr5Te8 of varying thickness have a long-range ferromagnetic order with an out-of-plane easy axis. There is no obvious change of the Curie temperature when the thickness of Cr5Te8 decreases from 52.1 to 7.2 nm. Here, we construct diverse 2D non-van der Waals/van der Waals vertical heterostructures (Cr5Te8/graphene, Cr5Te8/h-BN, Cr5Te8/MoS2). A uniform moiré superlattice is formed in the heterostructure through a lattice mismatch. The successful growth of 2D Cr5Te8 and a related moiré superlattice introduces 2D non-van der Waals ferromagnets into moiré superlattice research, thus highlighting prospects for property investigation of a non-van der Waals magnetic moiré superlattice and massive applications which require a scalable approach to magnetic moiré superlattices.

Effects of Chlortetracycline Rumen-Protected Granules on Rumen Microorganisms and Its Diarrhea Therapeutic Effect.

Chlortetracycline is a broad-spectrum antibiotic used as an oral medication in ruminants. However, this antibiotic affects the rumen microbial population, thereby upsetting the normal microbiota of ruminants. This study determined whether our newly developed chlortetracycline rumen-protected granules are relatively harmless to rumen microorganisms while effective against lamb E. coli diarrhea. We used a qPCR assay to quantify selected rumen microorganisms from lambs treated with or without oral chlortetracycline. We also assessed bacterial diversity in the rumen by 16S rRNA gene sequencing. Lambs were divided into three groups: one group given with oral chlortetracycline granules for 7 days; one group with chlortetracycline premix; and one without treatment. Rumen fluid was collected on 0 d, 7 d, and 14 d of the experiment. In the therapeutic effect trial, cases of naturally E. coli-infected lamb with diarrhea were selected and divided into low, medium, and high dose groups of granules, premix, infection control, and healthy control groups. Treatments were continuously administered for 7 days, and animals were observed for 14 days after drug withdrawal to score and evaluate the treatment effect. Results of qPCR and 16S rRNA gene sequencing showed that the granules could diminish the impact of chlortetracycline on rumen microorganisms compared with the premix. The diarrhea therapeutic effect trial showed that the oral administration of the chlortetracycline rumen-protected granules at the dose of 30 mg/kg·bw/d for 7 days could effectively treat lamb diarrhea caused by E. coli. In conclusion, we provide a new drug preparation of chlortetracycline that can diminish the effect on the rumen microbiota while treating diarrhea caused by E. coli.

In vitro Dissolution Testing and Pharmacokinetic Studies of Silymarin Solid Dispersion After Oral Administration to Healthy Pigs.

We evaluated the pharmacokinetics of silymarin solid dispersion in pigs to determine whether silybin bioavailability would be increased over that of a silymarin premix. In vitro dissolution testing was conducted using dissolution apparatus 1 (baskets) at 100 rpm at 37 ± 0.5°C in pH 1.2 HCl, pH 6.8 phosphate, and pH 4.3 acetate buffers containing 0.5% Tween-80. In vivo pharmacokinetics were studied using 16 healthy pigs (Yorkshire × Landrace) that were randomly assigned to two groups. Silymarin as solid dispersion and premix dosage forms were administered directly by stomach tubes at 50 mg kg-1 silybin. In vitro dissolution of silybin for the premix was 35.02, 35.90, and 38.70% in these buffers, respectively. In contrast, silybin dissolution in solid dispersions was increased to 82.92, 87.48, and 99.70%, respectively. Silymarin solid dispersion administered at a single dose resulted in a peak concentration (Cmax) of 1,190.02 ± 246.97 ng ml-1 with the area under the curve (AUC0-∞) at 1,299.19 ± 67.61 ng ml-1 h. These parameters for the premix groups were 411.35 ± 84.92 ng ml-1 and 586.82 ± 180.99 ng ml-1 h, respectively. The Cmax and AUC0-∞ values for the solid dispersion were about twice that of the premix and were consistent with the in vitro dissolution data.