Bo Yang

Phytochemicals with antifungal activity against Fusarium graminearum (F. graminearum) are considered potential in-feed anti-mycotoxigenic agents that may complement conventional post-harvest control strategies. Therefore, we screened fourteen phytochemicals, including seven quinolizidine alkaloids (QAs), for anti-F. graminearum activity, evaluated their individual and combined efficacy in inhibiting mycelial growth, spore germination, and deoxynivalenol (DON) production, and explored the underlying mechanisms via transcriptomic analysis. Matrine (MT), sophoridine (SR), and sophocarpine (SC) exhibited antifungal activity against F. graminearum, with minimum inhibitory concentrations (MICs) of 5, 4, and 4 mg/mL, respectively. The three QAs at their MICs completely inhibited mycelial growth and DON production in liquid cultures, but were less effective on potato dextrose agar plates and in pig feed. Particularly pronounced antifungal activity and inhibitory effects on DON production were observed when the three QAs were applied in combination with berberine hydrochloride (BBR). The observed inhibition appears to be attributed to dysregulated expression of the TRI cluster genes and ERG biosynthesis genes, coupled with significant modulation of steroid biosynthesis (ko00100) and central carbon/lipid metabolism pathways. These findings provide preliminary experimental evidence supporting the further exploration of QA–BBR combinations to control fungal proliferation and DON accumulation in pig feed.

Resveratrol (RES) is a natural polyphenolic compound characterized by poor aqueous solubility and significant first-pass metabolism, resulting in extremely low oral bioavailability. Although resveratrol-loaded nanostructured lipid carriers (RES-NLCs) have shown potential in enhancing oral absorption, direct experimental evidence for their intestinal lymphatic transport mechanism remains limited, and existing explanations is largely based on indirect inference. RES-NLCs were prepared, and their pharmacokinetics and lymphatic transport characteristics were evaluated using a laboratory-established mesenteric lymph duct–jugular vein assisted reflux model in rats. Simultaneously, a 28-day repeated-dose toxicity study was conducted in ICR mice. Pharmacokinetic results showed that compared with RES-Sol, RES-NLCs increased Cmax by approximately 2.3-fold, improved relative bioavailability by 7-fold, and achieved an absolute bioavailability of 176%. The lymphatic transport model confirmed that RES-NLCs are absorbed via the intestinal lymphatic pathway. In the 28-day repeated-dose toxicity study, no mortality or obvious clinical symptoms were observed at a dose of 10 mg/kg. The RES-NLCs group exhibited increased liver coefficient and decreased spleen coefficient. Hematological analysis showed a mild increase in red blood cell count, along with decreases in mean corpuscular volume and red blood cell distribution width coefficient of variation. Serum biochemistry revealed significant elevations in aspartate aminotransferase and alanine aminotransferase (p = 9 × 10⁻⁵ and p = 4.02 × 10⁻⁷, respectively). However, no significant differences were observed in the organ coefficients of the heart, lungs, kidneys, or brain. Body composition and magnetic resonance imaging showed no abnormalities, and histopathological examination of major organs including the liver, stomach, and intestines revealed no structural damage. These findings provide direct evidence that RES-NLCs enhance the oral bioavailability by promoting intestinal lymphatic uptake, suggesting that this system may serve as an effective delivery platform for poorly soluble hydrophobic drugs.

Background: The in vivo efficacy and mechanisms of matrine (MT) in reversing β-lactam resistance in E. coli remain unclear. Methods: β-lactam-resistant E. coli strains were treated with MT both in vitro and in a murine intestinal colonization model. Phenotypic changes (MIC, morphology, growth, biofilm, β-lactamase) were evaluated, and transcriptomic profiles were analyzed. Results: MT at sub-inhibitory concentrations significantly and concentration-dependently reduced the MICs of β-lactam-resistant E. coli strains by 2- to 32-fold in vitro. This reduction was also confirmed in vivo, and its magnitude became more pronounced as the number of doses increased. MT treatment dispersed bacterial aggregates and dissipated extracellular matrix, but did not alter the morphology of individual bacteria. At concentrations above 1024 μg/mL, MT significantly inhibited bacterial growth; lower concentrations (≤512 μg/mL) had no effect. Notably, MT inhibited biofilm formation and β-lactamase production both in vitro and in vivo. Conclusions: MT restored the susceptibility of β-lactam-resistant E. coli to cefepime and cefquinome. This effect was associated with suppression of biofilm formation and β-lactamase production, which correlated with the downregulation of key genes (ycgR, pgaB, pgaD, bla_TEM and bla_CTX-M).

Background/Objectives: Curcumin (CUR), a natural polyphenol with poor solubility and significant first-pass metabolism, shows extremely low oral bioavailability. Although CUR-loaded nanostructured lipid carriers (CUR-NLCs) have demonstrated potential in enhancing oral absorption, direct evidence regarding their intestinal lymphatic transport mechanism remains insufficient, and current understanding largely relies on indirect speculation. Methods: CUR-NLCs were prepared by emulsion-ultrasonication and evaluated for their physicochemical properties including particle size, zeta potential, polydispersity index, encapsulation efficiency, drug loading, stability and release profile. A mesenteric lymph duct-jugular vein shunt rat model combined with transmission electron microscopy was employed to assess the pharmacokinetic behavior and lymphatic transport pathway. Results: CUR-NLCs had a mean size of 117.28 ± 1.32 nm, 99.99% encapsulation efficiency, and 1.73% drug loading. They exhibited good gastrointestinal stability and sustained release (max, and extended half-life (33.49 ± 3.15 h). CUR was detected only in the lymph of the CUR-NLCs group, confirming intestinal lymphatic transport. TEM revealed abundant chylomicrons (0.1–2 μm) in jejunal epithelial cells, providing morphological support. Conclusions: This study directly demonstrates that CUR-NLCs improve oral bioavailability via intestinal lymphatic absorption, offering a viable strategy for delivering poorly soluble hydrophobic drugs.

Bacterial intestinal infections, such as porcine colibacillosis, have caused large economic losses to the global pig industry every year

The study aimed to provide a possible strategy to evaluate the detoxifying efficacy of mycotoxin adsorbents in vivo by analyzing deoxynivalenol (DON) concentration in feces. Fifteen pigs were randomly assigned to five groups (groups A–E, 3 replicates/group). The pigs in each group were fed twice a day for 10 d with 500 g of designed diets (group A, commercial feedstuffs; group B, DON-contaminated (mildewed) feedstuffs; groups C, D, E, mildewed feedstuffs containing 0.2% adsorbent 1, 2, and 3, respectively). For each pig, 2-g fecal samples were collected pre-feeding and analyzed by ultra-performance liquid chromatography. Nondetectable or low concentrations of DON (20 μg/g) were detected in six out of twenty fecal batches from pigs in group C. Moderate concentrations of DON (5.54–6.50 μg/g) were detected in one out of twenty fecal batches from pigs in group D and two out of twenty in group E. Based on the predefined evaluation criteria, higher DON concentration and frequency in feces indicate better adsorbent efficacy. Notably, Absorbent 1 demonstrated a more pronounced detoxification efficacy in vivo compared to the other two absorbents.

Introduction: Matrine (MT) is a potential resistance reversal agent. However, it remains unclear whether MT can reverse the resistance of Haemophilus parasuis (H. parasuis) to β-lactams, and, if so, by what mechanism MT works.Methods: We screened one cefaclor (CEC)-resistant strain (clinical strain C7) from eight clinical (H. parasuis) strains and determined the underlying resistance mechanism. Then, we investigated the reversal effect of MTon the resistance of this strain to CEC.Results and Discussion: The production of β-lactamase, overexpression of AcrAB-TolC system, and formation of biofilm might not be responsible for the resistance of clinical strain C7 to CEC. Fourteen mutation sites were found in four PBP genes (ftsI, pbp1B, mrcA, and prcS) of clinical strain C7, among which the mutation sites located in ftsI (Y₁₀₃D and L₅₁₇R) and mrcA (A₆₃₉V) genes triggered the resistance to CEC. The minimum inhibitory concentration (MIC) of CEC against clinical strain C7 was reduced by two to eight folds after MT treatment, accompanied by the significant down-regulated expression of mutated ftsI and mrcA genes. Based on such results, we believed that MT could reverse the resistance of H. parasuis to CEC by inhibiting the mutations in ftsI and mrcA genes. Our research would provide useful information for restoring the antimicrobial activity of β-lactams and improving the therapeutic efficacy of Glässer’s disease.

A pharmacokinetic/pharmacodynamic (PK/PD) model was developed to optimize the dosing regimen of enrofloxacin (EN) againstGlaesserella parasuisin pigs. EN (2.5 mg/kg) was administered intramuscularly to eight healthy pigs and eight pigs that were experimentally infected withG. parasuisSW124. Blood samples were collected at predetermined time points. Plasma EN concentrations were determined, and the main PK parameters were estimated. The PD of EN againstG. parasuisSW124 was also investigated in vitro and ex vivo. The dynamic behaviour of EN in pigs was consistent with a one‐compartment model. Significant differences were observed between healthy and infected pigs in the area under the curve (AUC) (3.58 ± 0.94 and 5.39 ± 1.01 μg h/ml, respectively) and the systemic clearance (CL) (736.32 ± 171.46 and 479.36 ± 96.81 ml/h/kg, respectively), suggesting that the pathogenicity ofG. parasuisSW124 to pigs might alter the PK profile of EN, and therefore should be considered in dose optimization. Both the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were 0.125 μg/ml in tryptone soya broth (TSB) medium or plasma. The mutant prevention concentration (MPC) was 0.6 μg/ml. EN inhibited or killedG.parasuisSW124 in a concentration‐dependent manner. The targeted endpoints of AUC_24 h/MIC for bacteriostasis, bactericidal action, and eradication were 5.10, 7.34, and 8.65 h and 5.91, 9.01, and 10.90 h in healthy and infected pigs, respectively. The optimal doses were 3.58−6.08 mg/kg in healthy pigs and 2.71−4.99 mg/kg in infected pigs from the point of view of preventing drug resistance.