The Probiotic Effectiveness in Preventing Experimental Colitis Is Correlated With Host Gut Microbiota

Current evidence to support extensive use of probiotics in inflammatory bowel disease is limited and factors that contribute to the inconsistent effectiveness of clinical probiotic therapy are not completely known. Here, we used Bifidobacterium longum JDM 301 as a model probiotic to study potential factors that may influence the effect of probiotics in experimental colitis. We found that the effect of B. longum JDM 301 in tempering experimental colitis varied across individual mice even with the same genetic background. The probiotic efficacy was highly correlated with the host gut microbial community features. Consumption of a diet rich in fat could exacerbate mucosal injury-induced colitis but could not change the host responsiveness to B. longum JDM 301 treatment, suggesting of potential mechanistic differences between regulating colitis pathogenesis, and modulating probiotic efficacies by the gut microbiota. Together, our results suggest that personalized microbiome features may modify the probiotic therapeutic effect and support the idea of personalized probiotic medicine in inflammatory bowel disease

Automated measurement of cattle surface temperature and its correlation with rectal temperature

<div><p>The body temperature of cattle varies regularly with both the reproductive cycle and disease status. Establishing an automatic method for monitoring body temperature may facilitate better management of reproduction and disease control in cattle. Here, we developed an Automatic Measurement System for Cattle’s Surface Temperature (AMSCST) to measure the temperature of metatarsus by attaching a special shell designed to fit the anatomy of cattle’s hind leg. Using AMSCST, the surface temperature (ST) on the metatarsus of the hind leg was successively measured during 24 hours a day with an interval of one hour in three tested seasons. Based on ST and rectal temperature (RT) detected by AMSCST and mercury thermometer, respectively, a linear mixed model was established, regarding both the time point and seasonal factors as the fixed effects. Unary linear correlation and Bland-Altman analysis results indicated that the temperatures measured by AMSCST were closely correlated to those measured by mercury thermometer (R² = 0.998), suggesting that the AMSCST is an accurate and reliable way to detect cattle’s body temperature. Statistical analysis showed that the differences of STs among the three seasons, or among the different time points were significant (<i>P</i><0.05), and the differences of RTs among the different time points were similarly significant (<i>P</i><0.05). The prediction accuracy of the mixed model was verified by 10-fold cross validation. The average difference between measured RT and predicted RT was about 0.10 ± 0.10°C with the association coefficient of 0.644, indicating the feasibility of this model in measuring cattle body temperature. Therefore, an automated technology for accurately measuring cattle body temperature was accomplished by inventing an optimal device and establishing the AMSCST system.</p></div

Installation diagram of the data detection device of AMSCST.

<p>Installation diagram of the data detection device of AMSCST.</p

Consistency of temperature measured by AMSCST and mercury thermometer.

<p>A. The linear curve of the measured temperature of AMSCST and mercury thermometer; B. Bland and Altman plot showing agreement between measurements obtained by the mercury thermometer (as the reference) and AMSCST.</p

The mean ST and RT in different days and different seasons (°C).

<p>The mean ST and RT in different days and different seasons (°C).</p

Development and validation of a UPLC–MS/MS assay for the determination of gemcitabine and its L-carnitine ester derivative in rat plasma and its application in oral pharmacokinetics

A simple and rapid UPLC–MS/MS method to simultaneously determine gemcitabine and its L-carnitine ester derivative (2'-deoxy-2', 2'-difluoro-N-((4-amino-4-oxobutanoyl) oxy)-4-(trimethyl amm-onio) butanoate-cytidine, JDR) in rat plasma was developed and validated. The conventional plasma sample preparation method of nucleoside analogues is solid-phase extraction (SPE) which is time-consuming and cost-expensive. In this study, gradient elution with small particles size solid phase was applied to effectively separate gemcitabine and JDR, and protein precipitation pretreatment was adopted to remove plasma protein and extract the analytes with high recovery(>81%). Method validation was performed as per the FDA guidelines, and the standard curves were found to be linear in the range of 5–4000 ng/ml for JDR and 4–4000 ng/ml for gemcitabine, respectively. The lower limit of quantitation (LLOQ) of gemcitabine and JDR was 4 and 5 ng/ml, respectively. The intra-day and inter-day precision and accuracy results were within the acceptable limits. Finally, the developed method was successfully applied to investigate the pharmacokinetic studies of JDR and gemcitabine after oral administration to rats

Combination of l‑Carnitine with Lipophilic Linkage-Donating Gemcitabine Derivatives as Intestinal Novel Organic Cation Transporter 2‑Targeting Oral Prodrugs

Novel organic cation transporter 2 (OCTN2, <i>SLC22A5</i>) is responsible for the uptake of carnitine through the intestine and, therefore, might be a promising molecular target for designing oral prodrugs. Poor permeability and rapid metabolism have greatly restricted the oral absorption of gemcitabine. We here describe the design of intestinal OCTN2-targeting prodrugs of gemcitabine by covalent coupling of l-carnitine to its N4-amino group via different lipophilic linkages. Because of the high OCTN2 affinity, the hexane diacid-linked prodrug demonstrated significantly improved stability (3-fold), cellular permeability (15-fold), and oral bioavailability (5-fold), while causing no toxicity as compared to gemcitabine. In addition, OCTN2-targeting prodrugs can simultaneously improve the permeability, solubility, and metabolic stability of gemcitabine. In summary, we present the first evidence that OCTN2 can act as a new molecular target for oral prodrug delivery and, importantly, the linkage carbon chain length is a key factor in modifying the affinity of the substrate for OCTN2