The effect of alginate oligosaccharides on intestine barrier function and Vibrio parahaemolyticus infections in the white shrimp Litopenaeus vannamei.

The intestine is a host-pathogen interaction site and improved intestinal barrier function help to prevent disease in shrimp. Alginate oligosaccharides (AOS) are derived from resourceful brown algae. The intestine protection properties of AOS were widely recognized, and their benefits in fish have been reported. Nevertheless, there are no reports on AOS in shrimp and other crustaceans. In the present work, we measured the effects of AOS on growth performance and disease resistance in the white shrimp Litopenaeus vannamei and investigated their effects on intestinal health. Shrimps with an initial weight of about 2 g were fed with diets supplemented with 0 (control), 0.07%, 0.2%, 0.6%, or 1.2% of AOS for 56 days and were sampled and challenged with Vibrio parahaemolyticus. Dietary AOS did not significantly influence weight gain or feed utilization (P > 0.05). However, AOS considerably decreased the seven-day cumulative mortality after the challenge at any dose (P < 0.05). Dietary AOS improved the intestinal structure, significantly boosted the intestinal villus height at 0.6% and 1.2% levels, and increased intestinal wall thickness by 0.2%, 0.6%, and 1.2%. The alkaline phosphatase and maltase activities were also increased, suggesting that AOS improved the intestinal condition. Redox homeostasis in intestinal was improved by AOS, as expressed by the enhanced total antioxidant capacity and decreased malonaldehyde content, partly due to the increased superoxide dismutase and catalase activities. Compared with the antioxidant system, AOS's stimulating effects on immunity were more significant. At any level, AOS significantly activated lysozyme activity, the expression of propo and two antimicrobial peptide genes (pen-3 and crusin). However, the lowest concentration of AOS did not stimulate the gene expression of all three assayed pattern recognition receptors (LGBP, Toll, and IMD), and only the highest concentration of AOS increased the expression of imd. These findings suggest that AOS are highly efficient immunostimulants, and various immune pathways in shrimp are differentially sensitive to AOS. Finally, our findings suggest that AOS significantly alter the gut microbiota and their relative abundance at the phylum, family, and genus levels. In conclusion, AOS significantly enhances disease resistance in L. vannamei, possibly attributed to improved intestinal development, increased intestinal immunity and altered microbiota. These findings could provide a basis for future studies on the practical use of AOS and its mechanisms of action.

The efficacy and safety of ceftolozane-tazobactam in the treatment of GNB infections: a systematic review and meta-analysis of clinical studies.

BACKGROUND: Ceftolozane-tazobactam is a novel cephalosporin/ß-lactamase inhibitor combination with activity against Gram-negative bacteria (GNB). We aimed to comprehensively evaluate the clinical efficacy and safety of ceftolozane-tazobactam in treating GNB infections in adult patients. RESEARCH DESIGN AND METHODS: PubMed, Embase, and Cochrane databases were retrieved until August 2022. Randomized trials and non-randomized controlled studies evaluating ceftolozane-tazobactam and its comparators in adult patients with GNB infections were included. RESULTS: A total of 13 studies were included. Overall, patients receiving ceftolozane-tazobactam had significant advantages in clinical cure (odds ratio [OR], 1.62; 95% CI, 1.05-2.51) and microbiological eradication (OR, 1.43; 95% CI, 1.19-1.71), especially in Pseudomonas aeruginosa-infected patients. Ceftolozane-tazobactam had a significant advantage in clinical success or microbial eradication compared with polymyxin/aminoglycosides (PL/AG) or levofloxacin. There were no significant differences in adverse events (AEs), Clostridium difficile infection (CDI), and mortality between ceftolozane-tazobactam and comparators. Notably, ceftolozane-tazobactam showed a significantly lower risk of acute kidney injury compared with PL/AG. CONCLUSIONS: Ceftolozane-tazobactam showed excellent clinical and microbiological efficacy in treating GNB, especially P. aeruginosa-induced infections. The overall safety profile of ceftolozane-tazobactam was comparable to other antimicrobials, with no increased risk of CDI and obvious advantage over antibacterial agents with high nephrotoxicity.

Protective effects of glutamine against soy saponins-induced enteritis, tight junction disruption, oxidative damage and autophagy in the intestine of Scophthalmus maximus L.

Soy saponins, as thermo-stable anti-nutrients in soybean meal (SBM), are the primary causal agents of SBM-induced enteritis, which represents a well-documented pathologic alternation involving the distal intestines of various farmed fish. Our previous work showed that soy saponins might lead to SBM-induced enteritis, destroy tight junction structure and induce oxidative damage in juvenile turbot. Glutamine, as a conditionally essential amino acid, is an important substrate utilized for the growth of intestinal epithelial cells. An 8-week feeding trial was carried out to determine whether glutamine can attenuate the detrimental effects of soy saponins. Three isonitrogenous-isolipidic experimental diets were formulated as follows: (i) fish meal-based diet (FM), considered as control; (ii) FM + 10 g/kg soy saponins, SAP; and (iii) SAP + 15 g/kg glutamine, GLN. The results showed that dietary soy saponins significantly increased the gene expression levels of inflammatory markers (IL-1ß, IL-8 and TNF-α) and related signaling factors (NF-кB, AP-1, p38, JNK and ERK), which were remarkably attenuated by dietary glutamine. Compared to SAP group, GLN-fed fish exhibited significantly higher expression levels of tight junction genes (CLDN3, CLDN4, OCLN, Tricellulin and ZO-1). Glutamine supplementation in SAP diet markedly suppressed the production of reactive oxygen species, malondialdehyde and protein carbonyl, and enhanced the activities of antioxidant enzymes as well as the mRNA levels of HO-1, SOD, GPX and Nrf2. Furthermore, GLN-fed fish had a remarkably lower number of autophagosomes compared to SAP-fed fish. In conclusion, our study indicated that glutamine could reverse the harmful effects of soy saponins on intestinal inflammation, tight junction disruption and oxidative damage, via attenuation of NF-кB, AP-1 and MAPK pathways and activation of Nrf2 pathway. Glutamine may have the function of controlling autophaghic process within an appropriate level of encountering inflammation.

Chitosan and chitooligosaccharides attenuate soyabean meal-induced intestinal inflammation of turbot (Scophthalmus maximus): possible involvement of NF-кB, activator protein-1 and mitogen-activated protein kinases pathways.

An 8-week feeding experiment was conducted to investigate and confront the putative functions of chitosan (CTS) and chitooligosaccharide (COS) in the growth and homoeostasis of distal intestine in juvenile turbots fed diets containing soyabean meal (SBM). Three isolipidic and isonitrogenous diets were formulated by supplemented basal diet (based on a 400 g/kg SBM) with 7·5 g/kg CTS or with 2·0 g/kg COS. Our results indicated that both CTS and COS supplementation could significantly improve (i) the growth performance and feed efficiency ratio; (ii) antioxidant activity driven by metabolic enzymes (i.e. catalase, glutathione reductase, glutathione peroxidase and superoxide dismutase); (iii) glutathione levels; (iv) acid phosphatase and lysozyme activity and (v) IgM content. As a result, these two particular prebiotics were able to significantly attenuate the histological alterations due to local inflammation as well as to decrease the transcriptional levels of proinflammatory cytokines (i.e. IL-1ß, IL-8 and TNF-α) and major pathway effectors (i.e. activator protein-1 (AP-1), NF-кB, p38 mitogen-activated protein kinase, c-Jun N-terminal kinase and extracellular regulated kinase). High-throughput sequencing data indicated that dietary CTS and COS could significantly decrease the diversity of intestinal bacteria but elevate the relative abundances of Bacillus, Lactobacillus and Pseudomonas genera. Altogether, these findings suggest that CTS and COS can improve growth of turbot, enhance intestinal immune and anti-oxidant systems and promote the balance of intestinal microbiota. The protective effects, elicited by these two prebiotics, against SBM-induced inflammation could be attributed to their roles in alleviating the overexpression of inflammatory cytokines by possibly down-regulating NF-кB, AP-1 and/or mitogen-activated protein kinases pathways.

Corn gluten meal induces enteritis and decreases intestinal immunity and antioxidant capacity in turbot (Scophthalmus maximus) at high supplementation levels.

Corn gluten meal (CGM) is an important alternative protein source in aquafeed production. However, in turbot (Scophthalmus maximus), CGM could not be effectively utilized because of its low digestibility, the reason for which is still unclear. The purpose of the present study was to investigate and elucidate the cause for the poor utilization of CGM by turbot from the view of gut health. An 8-week feeding trial was conducted with turbot individuals (initial body weight 11.4 ± 0.2 g), which were fed with one of four isonitrogenous and isolipidic diets formulated to include 0%, 21.2%, 31.8%, and 42.6% CGM to progressively replace 0%, 33%, 50%, and 67% fish meal (FM) protein in a FM-based diet, respectively. The results showed that CGM caused dose-dependent decreases in (1) growth performance, nutrient digestibility, and feed utilization; (2) activities of brush-border membrane enzymes; (3) intestinal antioxidant indices of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase activities, and reduced glutathione level; (4) intestinal immune parameters of acid phosphatase activity, complement 3, complement 4, and IgM concentrations. Dose-dependent increases in the severity of the inflammation, with concomitant alterations on microvilli structure and increasing expression of inflammatory cytokine genes of Il-1ß, Il-8, and Tnf-α were observed but without a change in the intracellular junctions and the epithelial permeability established by the plasma diamine oxidase activity and D-lactate level examinations. In conclusion, the present work proved that CGM negatively affected the gut health of turbot by inducing enteritis and by decreasing intestinal immunity and antioxidant capacity, which could be one of the reasons for the reduced utilization of CGM by turbot.

Protective effect of glutamine and arginine against soybean meal-induced enteritis in the juvenile turbot (Scophthalmus maximus).

Soybean meal can induce enteritis in the distal intestine (DI) and decrease the immunity of several cultured fish species, including turbot Scophthalmus maximus. Glutamine and arginine supplementation have been used to improve immunity and intestinal morphology in fish. This study was conducted to investigate the effects of these two amino acids on the immunity and intestinal health of turbot suffering from soybean meal-induced enteritis. Turbots (initial weight 7.6 g) were fed one of three isonitrogenous and isolipidic diets for 8 weeks: SBM (control diet), with 40% soybean meal; GLN, SBM diet plus 1.5% glutamine; ARG, the SBM diet plus 1.5% arginine. Symptoms that are typical of soybean meal-induced enteritis, including swelling of the lamina propria and subepithelial mucosa and a strong infiltration of various inflammatory cells was observed in fish that fed the SBM diet. Glutamine and arginine supplementation significantly increased (1) the weight gain and feed efficiency ratio; (2) the height and vacuolization of villi and the integrity of microvilli in DI; (3) serum lysozyme activity, and the concentrations of C3, C4, and IgM. These two amino acids also significantly decreased the infiltration of leucocytes in the lamina propria and submucosa and the expression of inflammatory cytokines including il-8, tnf-α, and tgf-ß. For the mucosal microbiota, arginine supplementation significantly increased microbiota community richness and diversity, and glutamine supplementation significantly increased the relative abundance of Lactobacillus and Bacillus. These results indicate that dietary glutamine and arginine improved the growth performance, feed utilization, and distal intestinal morphology, activated the innate and adaptive immune systems, changed the intestinal mucosal microbiota community, and relieved SBMIE possibly by suppression of the inflammation response.

Role and mechanism of Sophoridine on proliferation inhibition in human glioma U87MG cell line.

Sophoridine, a natural product obtained from medicinal plants, which has a variety of pharmacological effects, including anti-cancer effects, and selectively induces apoptotic cell death in a variety of human cancer cells in vitro and in vivo; however, its mechanism of action needs to be further elaborated. In this study, we investigated the effects of Sophoridine on the induction of apoptosis in human Glioma U87MG cells. Here, we found that Sophoridine can significantly inhibited cell proliferation, G2/M phase arrest, induced cell apoptosis and caused reactive oxygen species (ROS) generation and GSH content reduction. Sophoridine also triggered significant down-regulated the expression of p27, CDK2, Survivin, Livin, Bcl-2, E2F1 and the transcriptional activity of FoxM1, NF-κb and AP-1, meanwhile, up-regulated the expression of caspase-3/8, p53, Smac, c-JNK and p38-MAPK. Moreover, we found that Sophoridine significantly inhibited ubiquitin-proteasome in tumor cells. In conclusion, Sophoridine shows obvious anti-cancer activity on glioma cells by inducing cell apoptosis, inducing ROS accumulation, and activating mitochondrial signal pathways. Eventually, we believe Sophoridine could be used as a new drug for the treatment of glioma.

A pharmacodynamic simulation to evaluate tigecycline in treatment of nosocomial pneumonia caused by multidrug-resistant Acinetobacter baumannii.

The shortage of effective antibiotics against multidrug-resistant Acinetobacter baumannii (MDR-Ab) has posed great threat to the public health. But the advent of tigecycline gives us new hope. The goal of our research was to assess the clinical efficacy of tigecycline at different doses by using a pharmacokinetic/pharmacodynamic (PK/PD) model which can incorporate pharmacokinetic data of tigecycline from patients with pneumonia and MICs of MDR-Ab from a tertiary hospital. A 10000-patient Monte-Carlo Simulation based on the PK/PD model was conducted to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of tigecycline. 97% isolates displayed susceptibility and 3% were tigecycline-intermediate strains and the values of MIC ranged from 0.125 to 4 µ g/ml. A CFR of 61.62% was predicted for tigecycline at current dosage (50 mg q12h). When the dosage was increased, the predicted CFRs for 75 mg q12h, 100 mg q12h, 125 mg q12h, 150 mg q12h were 81.00%, 89.86%, and 94.57%, 96.77%, respectively. Despite presented higher susceptibility, the CFR obtained was not optimal at current dosage. A higher CFR indicating a better clinical efficacy can be gained by the increased dosage.

Treatment of community-acquired pneumonia with moxifloxacin: a meta-analysis of randomized controlled trials.

Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality throughout the world. To investigate whether moxifloxacin monotherapy is associated with better clinical outcomes than other antibiotics recommended for CAP among adults with mild-to-moderate or severe CAP, we performed a meta-analysis. MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched for randomized control trials (RCTs). The efficacy and safety of moxifloxacin were compared with other antimicrobial agents used to treat CAP. Fourteen RCTs, consisting of 6923 total patients, were included in the meta-analysis. No difference was found regarding the incidence of adverse events and mortality between moxifloxacin and the compared regimens. We found that moxifloxacin is as effective and well-tolerated as other recommended antibiotics for the treatment of CAP and possesses a better pathogen eradication rate than beta-lactam-based therapy.

Effects of dietary ß-glucan, mannan oligosaccharide and their combinations on growth performance, immunity and resistance against Vibrio splendidus of sea cucumber, Apostichopus japonicus.

A 4-week feeding trial was conducted to investigate the effects of dietary ß-glucan, mannan oligosaccharide (MOS) and their combinations on growth performance, immunity and disease resistance of sea cucumber Apostichopus japonicus. Sea cucumbers (1215 individuals with initial weight of 3.8 ± 0.2 g) were fed nine practical diets according to a 3 × 3 factorial design: the basal diet as the control supplemented with three levels of ß-glucan (0, 0.075, 0.15% w/w), crossed with 0, 0.1% (w/w) or 0.2% (w/w) MOS. Immune indices including total coelomocytes count (TCC), phagocytosis, superoxide anion production, superoxide dismutase (SOD) activity and total nitric oxide synthase activity (T-NOS) were measured at days 7, 11, 15, 18, 22, 25 and 29. At the end of the feeding trial, all the sea cucumbers left were weighted to monitor growth, and then were challenged by Vibrio splendidus. The results showed that dietary ß-glucan, MOS and their combinations significantly increased TCC, phagocytosis, superoxide anion production and SOD activity of sea cucumbers (P < 0.05). Only 0.15% ß-glucan and the combinations of ß-glucan and MOS significantly increased the T-NOS activity (P < 0.05). A synergistic effect was found between dietary ß-glucan and MOS. Moreover, combinations of ß-glucan and MOS prolonged the high levels of immune indices compared with ß-glucan or MOS supplementation alone. Except the 0.15% ß-glucan group, all the other treatments showed significantly lower cumulative mortality compared with control (P < 0.05). Furthermore, combination of 0.15% ß-glucan and 0.1% MOS had the best effects on enhancing disease resistance of sea cucumber. All treatments showed significantly higher specific growth rate (SGR) compared with control (P < 0.05), and the combination of 0.15% ß-glucan and 0.1% MOS was significantly higher than other treatments (P < 0.05). In conclusion, our results confirm the potential of ß-glucan and MOS as dietary immunostimulants and the synergistic effects of ß-glucan and MOS on A. japonicus.

[Isolation and identification of major steroidal saponins of Paris polyphylla Smith var stenophylla Franch].

OBJECTIVE: To research the steroidal saponins of Paris polyphylla Smith var stenophylla Franch for enriching the resource of Radix Paridis. METHODS: Compounds were isolated by silica gel, macroporous adsorption resin,Sephadex LH-20 and RP-C18 column chromatography and the structures were elucidated on the basis of spectroscopic methods. RESULTS: Five kinds of steroidal saponins were isolated and identified as follows: paris saponin I (1) Diosgenin-3-O-alpha-L-rhamnopyranosyl-(1 --> 2)-[alpha-L-arabinofuranosyl-(1 --> 4 )]-beta-D-Glucopyranoside, paris saponin V (2) Diosgenin-3-O-alpha-L-rhamnopyranosyl-(1 --> 2)-beta-D-glucopyranoside, paris saponin VI (3) Pennogenin-3-O-alpha-L-rhamnopyranosyl-(1 --> 2)-beta-D-glucopyranoside, paris saponin VII (4) Pennogenin-3-O-alpha-L-rhamnopyranosyl-(1 --> 4)-alpha-L-rhamnopyranosyl- 1 --> 4)-[alpha-L-rh-amnopyranosyl-(1 --> 2)]-beta-D-glucopyranoside, paris saponin H (5) Pennogenin-3-O-alpha-L-rhamnopyranosyl-(1 --> 2)-[alpha-L-arabinofuranosyl-(1 --> 4)]-beta-D-Glucopyranoside. CONCLUSION: All the five kinds of steroidal saponins were isolated from P. polyphylla. Smith var stenophylla Franch for the first time.

High-performance liquid chromatographic fingerprint analysis for different origins of sea buckthorn berries.

Using high-performance liquid chromatography (HPLC), a chemical fingerprint method was developed for investigating and demonstrating the variance of flavonoids among different origins of sea buckthorn berries. Thirty-four samples were analyzed including 15 RS (Hippophae rhamnoides ssp. sinensis) samples, 7 RY (H. rhamnoindes ssp. yunnanensis) samples, 5 RW (H. rhamnoides ssp. wolongensis) samples, 4 NS (H. neurocarpa ssp. stellatopilosa) samples and 3 TI (H. tibetana) samples. In the HPLC chromatograms, 12 compounds were identified as flavonoids, including quercetin 3-O-sophoroside-7-rhamnoside, kaempferol 3-O-sophoroside-7-O-rhamnoside, isorhamnetin 3-O-sophoroside-7-O-rhamnoside, isorhamnetin 3-O-glucoside-7-O-rhamnoside, quercetin 3-O-rutinoside, quercetin 3-O-glucoside, isorhamnetin 3-O-rutinoside, isorhamnetin 3-O-glucoside, quercetin, kaempferol 7-O-rhamnoside, kaempferol and isorhamnetin. Both correlation coefficient of similarity in chromatograms and relative peak areas of characteristic compounds were calculated for quantitative expression of the HPLC fingerprints. Our results revealed that the chromatographic fingerprint combining similarity evaluation could efficiently identify and distinguish sea buckthorn berries from different species. However, no obvious difference between RS and RY suggested that the two subspecies might have very close relationship in terms of chemotaxonomy. The established method was considered to be suitable for fingerprint analysis to check the genuine origin and control the quality of sea buckthorn berries and extracts.

[Characteristic changes of vascular tension factors in diabetic arterial occlusion of lower extremities].

OBJECTIVE: To study the change of vascular tension factors (VTF), including vascular contractile factors as endothelin-1 (ET-1), thromboxane A2 (TXA2) and vascular dilatory factors as nitric oxide (NO), prostacyclin (PGI2), in different stage of peripheral diabetic arterial occlusion (PDAO), and to preliminarily explore the clinical significance of these changes. METHODS: VTF in 40 diabetic patients, 15 of 2nd stage and 25 of 3rd stage, were observed by measuring level of ET-1, NO, TXB2 and 6-keto-PGF1alpha in blood plasma with RIA assay. RESULTS: (1) ET-1 and TXB2 levels in all patients were higher than those in control (P < 0.05 and P < 0.01), those in patients of 3rd stage was higher than those of 2nd stage, showing significant difference (P < 0.05). (2) NO and 6-keto-PGF1alpha levels in all patients was lower than those in control, but showed no significant difference between patients of various stages (P > 0.05). CONCLUSION: There are changes of VTF in patients with PDAO, manifesting as increase of vascular contractive factors and decrease of vascular dilative factor. The changes are diffrent in various stages, the vascular contractive and thrombotic factors in patients of 3rd stage are higher than those in patients of 2nd stage, but the injury on vascular dilative factors in the two stages showed insignificant difference.