The in vitro studies of triptolide with CYP isoforms and P-gp indicate that triptolide has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP1A2 and CYP3A4. Further clinical studies are needed to evaluate the significance of this interaction.
1. The aim of this study was to investigate the effects of glycyrrhizin on the pharmacokinetics of celastrol in rats. 2. Twelve male Sprague-Dawley rats were randomly assigned to two groups: control group and test group. Test group was pretreated with glycyrrhizin at a dose of 100 mg/kg/day for 10 days, and then the two groups were orally administered with celastrol at a dose of 1 mg/kg. The concentration of celastrol was determined using a sensitive and reliable LC-MS method. 3. The results showed that glycyrrhizin could significantly decrease the plasma concentration (from 64.36 ng/mL to 38.42 ng/mL) and AUC (from 705.39 to 403.43 μg·h/L) of celastrol in rats. To investigate its potential mechanism, the effects of glycyrrhizin on the transport and metabolic stability of celastrol were investigated using Caco-2 cell monolayer transwell model and rat liver microsome incubation systems. The Caco-2 cell monolayer transwell experiments indicated that glycyrrhizin could increase the efflux ratio of celastrol (4.02 versus 6.51). However, the rat liver microsome incubation experiments showed that glycyrrhizin could significantly increase the intrinsic clearance rate of celastrol from 20.3 ± 3.37 to 38.8 ± 4.18 μL/min/mg protein. 4. In conclusion, these results indicated that the herb-drug interaction between glycyrrhizin and celastrol might occur when they were coadministered.
Interleukin-8 (IL-8), the first known chemokine, is a CXC chemokine, which is cable of attracting neutrophils and inducing them to release lysozomal enzymes, triggering the respiratory burst. In the present study, the cDNA of an IL-8 was cloned from Japanese sea perch Lateolabrax japonicus (designated LjIL-8) by homology cloning and rapid amplification of cDNA ends (RACE) approaches. The full-length cDNA of LjIL-8 consisted of 803 nucleotides with a canonical polyadenylation signal sequence AATAAA and a poly(A) tail, and an open reading frame (ORF) of 300 bp encoding a polypeptide of 99 amino acid residues with a predicted molecular weight of 6.6 kDa. The high identity of LjIL-8 with IL-8 in other organisms indicated that LjIL-8 should be a new member of the IL-8 family. By fluorescent quantitative real-time PCR, mRNA transcript of LjIL-8 was detectable in all the examined tissues with higher level in spleen and head-kidney. The temporal expression of LjIL-8 mRNA in the spleen was up-regulated by lipopolyssacharide (LPS) stimulation and reached the maximum level at 6 h post-stimulation, and then dropped back to the original level gradually. These results indicated that LjIL-8 was a constitutive and inducible acute-phase protein that perhaps involved in the immune defense of L. japonicus.
INTRODUCTION: Congenital hypertrophic pyloric stenosis (CHPS), the most common infantile disease requiring surgical intervention, is routinely treated with open or laparoscopic pyloromyotomy. Recently, gastric peroral endoscopic pyloromyotomy (G-POEM) has been used for adult gastroparesis. We aimed to evaluate the efficacy and safety of G-POEM in treating infantile CHPS.
METHODS:We reviewed data from 21 G-POEM-treated patients at 3 tertiary children's endoscopic centers in China between January 2019 and December 2020. Clinical characteristics, procedure-related parameters, perioperative management, and follow-up outcomes were summarized.
RESULTS:G-POEM was performed successfully in all patients. The median operative duration was 49 (14-150) minutes. The submucosal tunnels were successfully established along the greater curvature of the stomach in 19 cases, and 2 cases were switched to the lesser curvature because of difficulty. No perioperative major adverse events occurred. Minor adverse events included inconsequential mucosal injury in 5 cases and unsatisfactory closure of the mucosal incision in 1 case. Upper gastrointestinal contrast radiography in all patients showed smooth passage of the contrast agent through the pylorus on postoperative day 3. The growth curves of the patients reached normal levels 3 months after the procedure. No recurrent clinical symptoms occurred in any patient during the median follow-up period of 25.5 (14-36) months.
DISCUSSION:G-POEM is feasible, safe, and effective for infants with CHPS, with satisfactory clinical responses over a short-term follow-up. Further multicenter studies should be performed to compare the long-term outcomes of this minimally invasive technique with open or laparoscopic pyloromyotomy.
The techniques of homology cloning and anchored PCR were used to clone the fucose-binding lectin (F-type lectin) gene from Japanese sea perch (Lateolabrax Japonicus). The full-length cDNA of sea perch F-lectin (JspFL) contained a 5' untranslated region (UTR) of 39 bp, an ORF of 933 bp encoding a polypeptide of 310 amino acids with an estimated molecular mass of 10.82 kDa and a 3' UTR of 332 bp. The searches for nucleotides and protein sequence similarities with BLAST analysis indicated that the deduced amino acid sequence of JspFL was homological to the Fucose-binding lectin in other fish species. In the JspFL deduced amino acid sequence, two tandem domains that exhibit the eel carbohydrate-recognition sequence motif were found. The temporal expressions of gene in the different tissues were measured by real-time PCR. And the mRNA expressions of the gene were constitutively expressed in tissues including spleen, head-kidney, liver, gill, and heart. The JspFL expression in spleen was different during the stimulated time point, 2 h later the expression level became up-regulated, and 6 h later the expression level became down-regulated. The result indicated that JspFL was constitutive and inducible expressed and could play a critical role in the host-pathogen interaction.
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