Evaluation of the Available Energy Value and Amino Acid Digestibility of Brown Rice Stored for 6 Years and Its Application in Pig Diets.

Long-term storage may reduce the nutritional quality of brown rice, so the present study aimed to evaluate the nutritional values of long-term-stored nutrition in pig diets. In Exp. 1, 18 Landrace × Yorkshire (L × Y) barrows with an initial body weight (IBW) of 25.48 ± 3.21 kg were randomly assigned to three treatments, including a corn-based diet, one-year-stored brown rice (BR1) diet, and six-year-stored brown rice (BR6) diet, to determine the digestible energy (DE) and metabolizable energy (ME) values of stored brown rice. In Exp. 2, 24 barrows (L × Y; IBW: 22.16 ± 2.42 kg) fixed with ileal T-cannula were randomly allotted to four dietary treatments, including a corn diet, two stored brown rice diets, and a nitrogen-free diet, to evaluate the amino acid (AA) digestibility of the stored brown rice. In Exp. 3 and 4, 108 crossbred weaned piglets (L × Y; IBW: 9.16 ± 0.89 kg) and 90 crossbred growing pigs (L × Y; IBW: 48.28 ± 3.51 kg) were allotted to three treatment diets, including a control diet and two stored brown rice diets, respectively, to investigate the application of stored brown rice in weaned piglets and fully grown pig diets. The results indicated that there was no significant difference in the DE and ME values between corn and stored brown rice (p > 0.05), while the apparent ileal digestibility (AID) of arginine, histidine, asparagine + aspartic acid (Asx), and the standardized ileal digestibility (SID) of arginine and histidine were higher in the stored brown rice diet compared to the corn diet (p < 0.05). Compared to the corn, the stored brown rice showed no significant effects on growth performance, nutrient-apparent total tract digestibility (ATTD), and serum biochemical indices (p > 0.05) but showed decreased activity in the various digestive enzymes in the duodenum, jejunum, and ileum of the weaned piglets (p < 0.05). Also, the stored brown rice diet showed no significant effects on growth performance, carcass traits, meat quality, as well as the fatty acid profiles in the longissimus dorsi muscle of fully grown pigs compared with the corn diet (p > 0.05). In conclusion, the brown rice stored for 6 years under good conditions had no obvious changes in the available energy and nutrient values. Although it may reduce digestive enzyme activity in the small intestines of the piglets, the stored brown rice showed no obvious adverse effects on growth performance and meat quality and can be effectively used in pig diets.

Multi-omics analysis reveals the molecular regulatory network underlying the prevention of Lactiplantibacillus plantarum against LPS-induced salpingitis in laying hens.

BACKGROUND: Salpingitis is one of the common diseases in laying hen production, which greatly decreases the economic outcome of laying hen farming. Lactiplantibacillus plantarum was effective in preventing local or systemic inflammation, however rare studies were reported on its prevention against salpingitis. This study aimed to investigate the preventive molecular regulatory network of microencapsulated Lactiplantibacillus plantarum (MLP) against salpingitis through multi-omics analysis, including microbiome, transcriptome and metabolome analyses. RESULTS: The results revealed that supplementation of MLP in diet significantly alleviated the inflammation and atrophy of uterus caused by lipopolysaccharide (LPS) in hens (P < 0.05). The concentrations of plasma IL-2 and IL-10 in hens of MLP-LPS group were higher than those in hens of LPS-stimulation group (CN-LPS group) (P < 0.05). The expression levels of TLR2, MYD88, NF-κB, COX2, and TNF-α were significantly decreased in the hens fed diet supplemented with MLP and suffered with LPS stimulation (MLP-LPS group) compared with those in the hens of CN-LPS group (P < 0.05). Differentially expressed genes (DEGs) induced by MLP were involved in inflammation, reproduction, and calcium ion transport. At the genus level, the MLP supplementation significantly increased the abundance of Phascolarctobacterium, whereas decreased the abundance of Candidatus_Saccharimonas in LPS challenged hens (P < 0.05). The metabolites altered by dietary supplementation with MLP were mainly involved in galactose, uronic acid, histidine, pyruvate and primary bile acid metabolism. Dietary supplementation with MLP inversely regulates LPS-induced differential metabolites such as LysoPA (24:0/0:0) (P < 0.05). CONCLUSIONS: In summary, dietary supplementation with microencapsulated Lactiplantibacillus plantarum prevented salpingitis by modulating the abundances of Candidatus_Saccharimonas, Phascolarctobacterium, Ruminococcus_torques_group and Eubacterium_hallii_group while downregulating the levels of plasma metabolites, p-tolyl sulfate, o-cresol and N-acetylhistamine and upregulating S-lactoylglutathione, simultaneously increasing the expressions of CPNE4, CNTN3 and ACAN genes in the uterus, and ultimately inhibiting oviducal inflammation.

Safety, tolerance, and pharmacokinetics of salvianolic acid B in healthy Chinese volunteers: A randomized, double-blind, placebo-controlled phase 1 clinical trial.

Background: Salvianolic acid B (Sal B) is one of the main active ingredients of Salvia miltiorrhiza Bunge. In China, many traditional Chinese medicines have been modified into injections for higher bioavailability and better efficacy. Salvianolic acid injection has been widely used in the clinic. Objective: This phase 1, randomized, double-blind, placebo-controlled, single-center study aimed to evaluate the safety, tolerance, and pharmacokinetics of Sal B injection in healthy Chinese volunteers. Methods: For the single-ascending-dose study, forty-seven healthy volunteers were randomly divided into 25, 75, 150, 200, 250, and 300 mg groups. For the multiple-ascending-dose study, sixteen healthy volunteers were randomly divided into 150 and 300 mg groups. In each group, volunteers were treated with Sal B or placebo randomly. Their safety was evaluated by a skin test, physical examination, vital sign, laboratory examination, 12-lead electrocardiogram, Holter, and clinical symptoms and signs. Blood samples were collected in 75, 150, and 300 mg single-ascending-dose study groups and 150 mg multiple-ascending-dose study groups to determine the concentration of salvianolic acid B. Results: In single-ascending-dose study groups, there were 41 adverse events in 24 cases (51.1%, 24/47). In multiple-ascending-dose study groups, there were 13 adverse events in eight cases (50.0%, 8/16). Sixty-six volunteers received the skin test, and three of them were excluded because of the positive result. Adverse events related to the treatment included increased alanine aminotransferase (4.0%), increased bilirubin (2.0%), increased creatinine kinase-MB (2.0%), increased brain natriuretic peptide (8.0%), increased urine N-acetyl-ß-D-glucosidase (4.0%), dizziness (2.0%), and chest discomfort (2.0%). No serious adverse events occurred. No volunteers withdrew from the trial. Peak plasma concentration and the area under the plasma concentration-time curve of salvianolic acid B progressively increased in a dose-dependent manner in 75, 150, and 300 mg single-ascending-dose study groups. There was no accumulation after 5 consecutive days of administration of 150 mg salvianolic acid B. Conclusion: Salvianolic acid B injections administered up to 300 mg in a single dose and 250 mg for 5 consecutive days showed excellent safety and tolerability in healthy Chinese volunteers. Clinical Trial Registration: www.chinadrugtrials.org.cn, identifier CTR20192236.

Effects of synbiotic on growth, digestibility, immune and antioxidant performance in broilers.

The overuse of in-feed antibiotics has been associated with serious issues, including the developing of antibiotic-resistant pathogens and causing drug residues in poultry products. To date, many countries have restricted the use of growth-promoting antibiotics in food animals, resulting in the increased need for effective alternatives to in-feed antibiotic. Synbiotics, which are composed of probiotics and prebiotics, have been shown to act synergistically when applied simultaneously. Thus, this study investigated the effects of a synbiotic, composed of microencapsulated Lactobacillus plantarum (MLP) and fructooligosaccharide (FOS), on growth, immune and antioxidant parameters, and digestibility of calcium and phosphorus in broilers. A total of 168 newly hatched male broilers were randomly allotted to three dietary groups (n = 7): (1) a corn-soybean meal basal diet (CON); (2) basal diet + synbiotic (SYN); and (3) basal diet + aureomycin (ANT). Compared with the CON, chickens had greater average daily gain and digestibility of calcium and phosphorus in the SYN group (P < 0.05). In the SYN and ANT group, serum IgA, IgG, and IL-10 levels were higher, while the serum TNF-α, IL-2, and IL-6 levels were reduced (P < 0.05) compared to CON. Compared with CON, the level of serum malondialdehyde was lower (P < 0.05) and SOD level was higher (P < 0.05) in either SYN or ANT group. No significant differences in populations of Escherichia coli were seen in chickens among the three groups, whereas, the populations of Lactobacillus were higher (P < 0.05) in chickens in the SYN group compared with those in CON and ANT groups. Taken together, the addition of SYN, consisting of MLP and FOS, had benefits on growth, immune and antioxidant parameters, and digestibility of calcium and phosphorus, indicating its potential to serve as a substitute for antibiotics in broiler feeding.

Pharmacokinetics and Bioequivalence of 2 Olanzapine Orally Disintegrating Tablet Products in Healthy Chinese Subjects Under Fed and Fasting Conditions.

To assess the bioequivalence of two 5-mg olanzapine orally disintegrating tablet (ODT) products, 2 randomized, open-label, single-dose, 2-way crossover studies were carried out under fasting or fed conditions. Blood samples were collected at scheduled times according to the study protocol. Statistical analysis of area under the concentration-time curve from time 0 to 168 hours (AUC0-t ), area under the curve from time zero to infinity (AUC0-∞ ), and peak plasma concentration (Cmax ) was conducted. Two formulations were considered bioequivalent if the 90% confidence intervals (CIs) of the geometric mean ratios for AUC0-t, AUC0-∞ , and Cmax were within the range of 0.80-1.25. Adverse events were recorded and evaluated throughout the studies. A total of 48 subjects with 24 in each study completed the 2 studies. In fasted subjects, the 90%CIs for the test product versus the reference product were 97.28%-105.13% for AUC0-t , 97.57%-105.54% for AUC0-∞ , and 90.94%-103.97% for Cmax . In fed subjects, the 90%CIs for AUC0-t , AUC0-∞ and Cmax were 99.73%-122.63%, 99.56%-121.75%, and 99.46%-120.46%, respectively. No serious adverse events were reported in the studies. The reference and the test product of 5-mg olanzapine ODT show comparable pharmacokinetic profiles under both fed and fasted conditions and were considered bioequivalent.

Pharmacokinetics and tolerability of cinitapride in healthy Chinese volunteers: a randomized, open-label, single- and multiple-dose study.

Cinitapride (CIN) is a drug for functional dyspepsia. The purpose of the study was to investigate the pharmacokinetics and tolerability of CIN in healthy Chinese volunteers. A randomized, open-label, single- and multiple-dose study was conducted in 12 healthy volunteers. Three different doses of CIN (1, 2, 4 tablets) were given to six groups in the single-dose study, and one tablet (1 mg) of CIN was administered three times a day in the multiple-dose study. Blood samples were collected at predetermined time intervals after CIN dosing and analyzed by LC-MS/MS. Eleven volunteers completed the study. After single dose, the Cmax and AUC of plasma increased approximately linearly with dosage; no statistically significant differences were found in pharmacokinetic parameters between three dose groups. After multiple doses, there was no significant change in Tmax and t1/2 compared with the results from the single dose. After repeated doses, AUC0-t and AUC0-∞ were increased, while CLz/F slightly decreased. And no differences between male and female. The pharmacokinetic parameters of this study were consistent with study results of non-Chinese subjects. Good tolerability was demonstrated in both single- and multiple-dose studies with dosage range from 1 to 4 mg in healthy Chinese subjects.

Pharmacokinetics and Bioequivalence Study of Hydroxychloroquine Sulfate Tablets in Chinese Healthy Volunteers by LC-MS/MS.

INTRODUCTION: Hydroxychloroquine (HCQ), 4-aminoquinoline, is an antimalarial drug and has become a basic therapy for rheumatic disease treatment. It can stabilize the condition of SLE patients and reduce the chances of patient relapse through its immunosuppressive function and antiinflammatory effects. This drug was absorbed completely and rapidly by oral administration, but has a prolonged half-life for elimination. The objective of this study was to evaluate the pharmacokinetic parameters and relative bioequivalence of a new generic (test) formulation with the branded (reference) formulation of HCQ in healthy Chinese male volunteers. This study was designed to acquire regulatory approval for the test formulation. METHODS: This study was conducted with a randomized, single-dose, two-period, and crossover design. The male subjects were randomly assigned to two groups at a 1:1 ratio to receive 0.2 g hydroxychloroquine sulfate tablets (0.1 g/piece) of the two formulations after a 3-month washout period then administered the alternate formulation. Study drugs were administered after overnight fasting (over 10 h). Plasma concentrations of hydroxychloroquine were measured by a validated LC-MS/MS method. The following pharmacokinetic properties were determined by a noncompartmental pharmacokinetic method: C max, T max, AUC0-t , AUC0-∝, and t 1/2. The bioequivalence between the test and reference products was assessed based on the following parameters: C max, AUC0-60d, and AUC0-∝ using the ANOVA method. If the 90% CI for AUC0-t was within 80-125% and for C max was within 70-143% of the statistical interval proposed by the SFDA, the two formulations were assumed bioequivalent. Concerning the main pharmacokinetic charateristics of hydroxychloroquine, a long half-life drug, the pharmacokinetic parameters of 0-72 h were determined according to the FDA. Furthermore, a comparison was made between the parameters at 0-60 days and 0-72 h to evaluate whether a truncated AUC method can be applied to estimate the relative bioavailability of HCQ. Tolerability was assessed by monitoring vital signs and laboratory tests and by questioning subjects about adverse events. RESULTS: The 90% CI of C max for HCQ is 103.8-142.3%; the AUC0-60 is 100-114.2% and AUC0-∝ 100-115.5%. Both met the criteria according to the SFDA's guidelines for bioequivalence. The relative bioavailability was 109.5% (according to AUC0-60d) and 110.7% (according to AUC0-∝). No serious or unexpected adverse events were observed. CONCLUSIONS: In this study, the pharmacokinetic studies and results were conducted so that the test and reference formulations of HCQ met the Chinese criteria for assuming bioequivalence. Both formulations were well tolerated in the population studies.

Modulation of pharmacokinetics of theophylline by antofloxacin, a novel 8-amino-fluoroquinolone, in humans.

AIM: To evaluate the pharmacokinetic interactions between theophylline and antofloxacin in vivo and in vitro. METHODS: A randomized, 5-day treatment and 3-way crossover design was documented in 12 healthy subjects. The subjects were orally administered with antofloxacin (400 mg on d 1 and 200 mg on d 2 to 5), theophylline (100 mg twice a day and morning dose 200 mg on d 1 and 5), or theophylline plus antofloxacin. The plasma and urinary pharmacokinetics of antofloxacin and theophylline were characterized after the first and last dose. The effect of antofloxacin on theophylline metabolism was also investigated in pooled human liver microsomes. RESULTS: The 5-day treatment with antofloxacin significantly increased the area of the plasma concentration-time curve and peak plasma concentration of theophylline, accompanied by a decrease in the excretion of theophylline metabolites. On the contrary, theophylline did not affect the pharmacokinetics of antofloxacin. In vitro studies using pooled human hepatic microsomes demonstrated that antofloxacin was a weak reversible and mechanism-based inhibitor of CYP1A2. The clinical interaction between theophylline and antofloxacin was further validated by the in vitro results. CONCLUSION: The results showed that antofloxacin increases the plasma theophylline concentration, partly by acting as a mechanism-based inhibitor of CYP1A2.

[The protective effects of ginsenoside RG1 and Rb1 against damage of HaCaT cells by ultraviolet B].

AIM: To investigate the survival rate and the level of HaCaT cells damage with ultraviolet B (UVB) radiation at various doses, and observe the protective effects of ginsenoside Rg1 and Rb1 in vitro. METHODS: MTT assay was employed to analyze the cell survival rate after UVB radiation of 30, 60, 90 and 120 mJ x cm(-2). The damage of nucleolus and the protective effects of ginsenoside Rg1 and Rb1 were scanned by Hoechst 33258 staining and single cell gel electrophoresis assay (SCGE). RESULTS: It was found that the cell survival rate decreased gradually and the damage of nucleolus aggravated as the radiation dose increased from 30 mJ x cm(-2) to 120 mJ x cm(-2). At the dose of 20 microg x mL(1-), obvious protective effect of ginsenoside Rg1 and Rb1 can be observed against UVB radiation-induced HaCaT cells growth inhibition and nucleolus damage. CONCLUSION: UVB radiation inhibits HaCaT human keratinocytes growth and ginsenoside Rg1 and Rb1 can relief the damage.