Zinc lactate alleviates oxidative stress by modulating crosstalk between constitutive androstane receptor signaling pathway and gut microbiota profile in weaned piglets.

This study aimed to determine the regulatory mechanism of dietary zinc lactate (ZL) supplementation on intestinal oxidative stress damage in a paraquat (PQ)-induced piglet model. Twenty-eight piglets (mean body weight 9.51 ± 0.23 kg) weaned at 28 d of age were randomly divided into control, ZL, PQ, and ZL + PQ groups (n = 7 in each group). The ZL-supplemented diet had little effect on growth performance under normal physiological conditions. However, under PQ challenge, ZL supplementation significantly improved average daily gain (P < 0.05) and reduced the frequency of diarrhea. ZL improved intestinal morphology and ultrastructure by significantly increasing the expression level of the jejunal tight junction protein, zonula occludens-1 (ZO-1) (P < 0.05), and intestinal zinc transport and absorption in PQ-induced piglets, which reduced intestinal permeability. ZL supplementation also enhanced the expression of antioxidant and anti-inflammatory factor-related genes and decreased inflammatory cytokine expression and secretion in PQ-induced piglets. Furthermore, ZL treatment significantly inhibited the activation of constitutive androstane receptor (CAR) signaling (P < 0.01) in PQ-induced piglets and altered the structure of the gut microbiota, especially by significantly increasing the abundance of beneficial gut microbes, including UCG_002, Ruminococcus, Rikenellaceae_RC9_gut_group, Christensenellaceae_R_7_group, Treponema, unclassified_Christensenellaceae, and unclassified_Erysipelotrichaceae (P < 0.05). These data reveal that pre-administration of ZL to piglets can suppress intestinal oxidative stress by improving antioxidant and anti-inflammatory capacity and regulating the crosstalk between CAR signaling and gut microbiota.

Dietary Soybean Oligosaccharides Addition Increases Growth Performance and Reduces Lipid Deposition by Altering Fecal Short-Chain Fatty Acids Composition in Growing Pigs.

One hundred and twenty-eight boars and gilts of the Duroc × Landrace × Yorkshire variety with an initial body weight (BW) of 52.49 ± 0.48 kg were used in a randomized complete block design for a 63-day experiment. The four treatment groups were: control diet (CON), CON + 0.2% soybean oligosaccharides (SBOS), CON + 0.4% SBOS, and CON + 0.8% SBOS. The results showed that the average daily weight gain (ADG) was significantly higher in the 0.8% SBOS group than in the CON group on days 0-63 (p < 0.05). Compared with the CON group, adding 0.8% SBOS to the diet significantly increased the carcass weight, dressing percentage, and carcass lean percentage, but decreased the average backfat depth of growing-finishing pigs (p < 0.05). Adding different concentrations (0.2%, 0.4%, and 0.8%) of SBOS to the diet can significantly increase the concentrations of acetate, propionate, and butyrate in feces (p < 0.05). The activities of malic enzyme and fatty acid synthase in the 0.8% group were significantly lower than those in the 0.2% and CON groups (p < 0.05). In summary, 0.8% SBOS supplementation to growing-finishing pigs' diets can reduce lipid deposition and increase ADG.

Dietary Taurine Improves Growth Performance and Intestine Health via the GSH/GSSG Antioxidant System and Nrf2/ARE Signaling Pathway in Weaned Piglets.

Early weaning of piglets was prone to increase reactive oxygen species, disrupt the redox balance, decrease antioxidant capacity, cause oxidative stress and intestinal oxidative damage, and lead to diarrhea in piglets. This research aimed to study dietary taurine (Tau) supplementation at a level relieving intestinal oxidative damage in early-weaned piglets. A total of 48 piglets were assigned to four groups of 12 individuals and fed a basal diet with 0.0% Tau (CON), 0.2% Tau (L-Tau), 0.3% Tau (M-Tau), or 0.4% Tau (H-Tau), respectively. The animal experiment lasted 30 days. The final weight, weight gain, average daily gain, and feed conversion rate increased with the increase in dietary Tau (Linear, p < 0.05; Quadratic p < 0.05), while the diarrhea index of piglets decreased with the increase in dietary Tau (Linear, p < 0.05). Serum malondialdehyde, nitric oxide (NO), D-lactose, and oxidized glutathione (GSSG) concentrations decreased with the increase in dietary Tau (Linear, p < 0.05). The O2•- and •OH clearance rate in serum, liver, and jejunum mucosa increased with the increase in dietary Tau (Linear, p < 0.05). Serum superoxide dismutase (SOD) activity, glutathione peroxidase (GPX) activity, catalase (CAT) activity, and peroxidase (POD) activity and total antioxidant capacity increased with the increase in dietary Tau (Linear, p < 0.05). The serum glutathione (GSH) concentration and the ratio of GSH to GSSG increased with the increase in dietary Tau (Linear, p < 0.05). The POD and glutathione synthase activity in the liver and jejunum mucosa increased with the increase in dietary Tau (Linear, p < 0.05). The mRNA abundances of HO-1 and GPX1 in the H-Tau group were higher than that in the L-Tau, M-Tau, and CON groups (p < 0.05). The mRNA abundances of SOD1 and Nrf2 in the M-Tau and H-Tau groups were higher than in the L-Tau and CON groups (p < 0.05). The mRNA abundance of SOD2 in the L-Tau, M-Tau, and H-Tau groups was higher than in the CON group (p < 0.05). The VH and the ratio of VH to CD of jejunum and ileum increased with the increase in dietary Tau (Linear, p < 0.05). The mRNA abundances of occludens 1 and claudin 1 in the H-Tau group were higher than that in the CON, L-Tau, and M-Tau (p < 0.05). The mRNA abundance of occludin in the L-Tau, M-Tau, and H-Tau groups was higher than that in CON (p < 0.05). The abundance of Firmicutes increased with the increase in dietary Tau (Linear, p < 0.05), while Proteobacteria and Spirochaetota decreased with the increase in dietary Tau (Linear, p < 0.05). Collectively, dietary supplementation of 0.3% and 0.4% Tau in feed could significantly improve the growth performance and enhance the antioxidant capacity of piglets.

Crosstalk between trace elements and T-cell immunity during early-life health in pigs.

With gradual ban on the use of antibiotics, the deficiency and excessive use of trace elements in intestinal health is gaining attention. In mammals, trace elements are essential for the development of the immune system, specifically T-cell proliferation, and differentiation. However, there remain significant gaps in our understanding of the effects of certain trace elements on T-cell immune phenotypes and functions in pigs. In this review, we summarize the specificity, development, subpopulations, and responses to pathogens of porcine T cells and the effects of functional trace elements (e.g., iron, copper, zinc, and selenium) on intestinal T-cell immunity during early-life health in pigs. Furthermore, we discuss the current trends of research on the crosstalk mechanisms between trace elements and T-cell immunity. The present review expands our knowledge of the association between trace elements and T-cell immunity and provides an opportunity to utilize the metabolism of trace elements as a target to treat various diseases.

Dietary Complex Probiotic Supplementation Changed the Composition of Intestinal Short-Chain Fatty Acids and Improved the Average Daily Gain of Growing Pigs.

At present, probiotics are being extensively evaluated for their efficacy as an alternative to antibiotics, and their safety in livestock production. In this study, 128 (Duroc, Yorkshire and Landrace) pigs with an average initial body weight of 28.38 ± 0.25 kg were allocated to four dietary treatments in a randomized complete-block design. There were eight pens per treatment, with four pigs per pen (two barrows and two gilts). Dietary treatments included: (1) control diet; (2) control diet + 0.05% complex probiotic; (3) control diet + 0.1% complex probiotic; (4) control diet + 0.2% complex probiotic. During the 28-day experimental period, the feeding of 0.1% complex probiotic in the diet increased body weight and average daily gain (p < 0.05). The addition of complex probiotics decreased total cholesterol and glucose concentrations in the blood (p < 0.01). Acetate concentrations in the blood increased from 0.1% complex probiotic in the diet (p < 0.05), while NH3 and H2S emissions in the feces decreased (p < 0.05) from 0.1% or 0.2% complex probiotic in the diet. In conclusion, dietary complex probiotic supplementation changed the composition of intestinal short-chain fatty acids and improved growth performance for growing pigs.

Improvement of Ulcerative Colitis by Aspartate via RIPK Pathway Modulation and Gut Microbiota Composition in Mice.

The intestine requires a great deal of energy to maintain its health and function; thus, energy deficits in the intestinal mucosa may lead to intestinal damage. Aspartate (Asp) is an essential energy source in the intestinal mucosa and plays a vital part in gut health. In the current study, we hypothesized that dietary supplementation of Asp could alleviate DSS-induced colitis via improvement in the colonic morphology, oxidative stress, cell apoptosis, and microbiota composition in a mouse model of dextran. Asp administration decreased the disease activity index, apoptosis, myeloperoxidase, eosinophil peroxidase, and proinflammatory cytokine (IL-1ß and TNF-α) concentrations in the colonic tissue, but improved the body weight, average daily food intake, colonic morphology, and antioxidant-related gene (GPX1 and GPX4) expression in DSS-treated mice. Expression levels of RIPK1 and RIPK3 were increased in the colon following Asp administration in the DSS-induced mice, whereas the MLKL protein expression was decreased. 16S rRNA sequencing showed that Asp treatment increased the abundance of Lactobacillus and Alistipes at the gene level, and Bacteroidetes at the phylum level, but decreased the abundance of Actinobacteria and Verrucomicrobia at the phylum level. Asp may positively regulate the recovery of DSS-induced damage by improving the immunity and antioxidative capacity, regulating RIPK signaling and modulating the gut microbiota composition.

Correlations of gestational hemoglobin level, placental trace elements content, and reproductive performances in pregnant sows.

The iron status of sows has a great influence on reproductive performance. Iron deficiency reduces reproductive performance and newborn piglet survival rate of sow. The hemoglobin is a potential predictor for the iron status of sows and is convenient for rapid detection in pig farms. However, the relationship between iron status, hemoglobin, placental trace elements, and reproductive performance remains unclear. In this study, the hemoglobin and reproductive performance of more than 500 sows with first to sixth parities at different gestation stages (25, 55, 75, 95, and 110 d of gestation) in two large-scale sow farms were collected, and the content of placental Fe, Zn, Mn, and Cu was analyzed. The results show that hemoglobin levels of sows during pregnancy (days 75, 95, and 110) decreased significantly (P < 0.001). As the parity increases, the hemoglobin levels of sows at days 25 and 55 of gestation and placental mineral element contents including Fe, Zn, Mn, and Cu at delivery decreased (P < 0.05), while the litter size, birth alive, and litter weights increased gradually (P < 0.001). Furthermore, hemoglobin during pregnancy had a negative linear correlation with litter weight and average weight (P < 0.05), and higher hemoglobin at day 25 of gestation may reduce the number of stillbirths (P = 0.05), but higher hemoglobin at day 110 of gestation may tend to be a benefit for the birth (P = 0.01). And there was a significant positive linear correlation between hemoglobin at day 110 of gestation and placental Fe and Mn levels (P = 0.002, P = 0.013). There was also a significant positive linear correlation among Fe, Zn, Mn, and Cu in the placenta (P < 0.001). The levels of Fe, Zn, and Mn in the placental at delivery were positively related to the average weight of the fetus (P = 0.048, P = 0.027, P = 0.047), and placental Cu was linearly correlated with litter size (P = 0.029). Our research revealed that the requirements for iron during gestation were varied in different gestation periods and parities. The feeds should be adjusted according to the gestation periods, parities, or iron status to meet the iron requirements of sows and fetal pigs.

Iron deficiency and iron excess may cause adverse outcomes during pregnancy. In sows' feed, iron is added as ferrous sulfate, ferrous glycine, or other forms to improve their reproductive performance and prevent iron-deficiency anemia in their offspring. However, it is always ineffective and iron-deficiency anemia often occurs in piglets. To explore the iron requirements in pregnant sows, we conducted a large-scale farm study to track the hemoglobin levels, placental trace element content, and reproductive performances of hundreds of sows. The correlation between the hemoglobin levels, placental trace element content, and reproductive performance indicators of sows during pregnancy at different parities was analyzed. We found that pregnancy hemoglobin level of sows decreases during the gestation and varies at different parities. The hemoglobin level of sows during pregnancy was linearly negatively correlated with reproductive performance. The content of iron, zinc, manganese, and copper in the placenta was linearly positively correlated. Our results revealed that iron deficiency or excess in sows' feed may not be conducive to the improvement of reproductive performance, and the optimal iron supplementation dose during pregnancy may depend on the iron status and number of fetuses of sow.

Effects of Dietary Zinc Sources on Growth Performance and Gut Health of Weaned Piglets.

The present study aimed to investigate the effects of dietary zinc sources on the growth performance and gut health of weaned piglets. In total, 96 Duroc × Landrace × Yorkshire (DLY) weaned piglets with an initial average body weight of 8.81±0.42kg were divided into four groups, with six replicates per treatment and four pigs per replicate. The dietary treatment groups were as follows: (1) control group, basal diet; (2) zinc sulphate (ZnSO4) group, basal diet +100mg/kg ZnSO4; (3) glycine zinc (Gly-Zn) group, basal diet +100mg/kg Gly-Zn and (4) zinc lactate group, and basal diet +100mg/kg zinc lactate. The whole trial lasted for 28days. Decreased F/G was noted in the Gly-Zn and zinc lactate groups (p<0.05). The zinc lactate group had a lower diarrhea rate than the control group (p<0.05). Moreover, the ZnSO4, Gly-Zn, and zinc lactate groups had significantly higher apparent total tract digestibility of dry matter (DM), crude protein (CP), ether extract (EE), crude ash, and zinc than the control group (p<0.05). The Gly-Zn and zinc lactate groups had higher jejunal villus height and a higher villus height:crypt depth ratio than the control group (p<0.05). In addition, the ZnSO4, Gly-Zn and zinc lactate groups had a significantly lower mRNA expression level of jejunal ZRT/IRT-like protein 4 (ZIP4) and higher mRNA expression level of jejunal interleukin-1ß (IL-1ß) than the control group (p<0.05). The mRNA expression level of jejunal zinc transporter 2 (ZNT2) was higher and that of jejunal Bcl-2-associated X protein (Bax) was lower in the Gly-Zn and zinc lactate groups than in the control group (p<0.05). Moreover, the zinc lactate group had a higher count of Lactobacillus spp. in the cecal digesta and higher mRNA expression levels of jejunal occludin and mucin 2 (MUC2) than the control group (p<0.05). In conclusion, dietary supplementation with 100mg/kg ZnSO4, Gly-Zn, or zinc lactate could improve the growth performance and gut barrier function of weaned piglets. Dietary supplementation with organic zinc, particularly zinc lactate, had the best effect.

The Associated Regulatory Mechanisms of Zinc Lactate in Redox Balance and Mitochondrial Function of Intestinal Porcine Epithelial Cells.

Zinc lactate (ZnLA) is a new organic zinc salt which has antioxidant properties in mammals and can improve intestinal function. This study explored the effects of ZnLA and ZnSO4 on cell proliferation, Zn transport, antioxidant capacity, mitochondrial function, and their underlying molecular mechanisms in intestinal porcine epithelial cells (IPEC-J2). The results showed that addition of ZnLA promoted cell proliferation, inhibited cell apoptosis and IL-6 secretion, and upregulated the mRNA expression and concentration of MT-2B, ZNT-1, and CRIP, as well as affected the gene expression and activity of oxidation or antioxidant enzymes (e.g., CuZnSOD, CAT, and Gpx1, GSH-PX, LDH, and MDA), compared to ZnSO4 or control. Compared with the control, ZnLA treatment had no significant effect on mitochondrial membrane potential, whereas it markedly increased the mitochondrial basal OCR, nonmitochondrial respiratory capacity, and mitochondrial proton leakage and reduced spare respiratory capacity and mitochondrial reactive oxygen (ROS) production in IPEC-J2 cells. Furthermore, ZnLA treatment increased the protein expression of Nrf2 and phosphorylated AMPK, but reduced Keap1 and p62 protein expression and autophagy-related genes LC3B-1 and Beclin mRNA abundance. Under H2O2-induced oxidative stress conditions, ZnLA supplementation markedly reduced cell apoptosis and mitochondrial ROS levels in IPEC-J2 cells. Moreover, ZnLA administration increased the protein expression of Nrf2 and decreased the protein expression of caspase-3, Keap1, and p62 in H2O2-induced IPEC-J2 cells. In addition, when the activity of AMPK was inhibited by Compound C, ZnLA supplementation did not increase the protein expression of nuclear Nrf2, but when Compound C was removed, the activities of AMPK and Nfr2 were both increased by ZnLA treatment. Our results indicated that ZnLA could improve the antioxidant capacity and mitochondrial function in IPEC-J2 cells by activating the AMPK-Nrf2-p62 pathway under normal or oxidative stress conditions. Our novel finding also suggested that ZnLA, as a new feed additive for piglets, has the potential to be an alternative for ZnSO4.

Glutamate and aspartate alleviate testicular/epididymal oxidative stress by supporting antioxidant enzymes and immune defense systems in boars.

Several potential oxidative agents have damaging effects on mammalian reproductive systems. This study was conducted to investigate the effects of glutamate (Glu) and aspartate (Asp) supplementation on antioxidant enzymes and immune defense systems in the outer scrotum of boars injected with H2O2. A total of 24 healthy boars were randomly divided into 4 treatment groups: control (basal diet, saline-treated), H2O2 (basal diet, H2O2-challenged outer scrotum (1 mL kg-1 BW)), Glu (basal diet +2% Glu, H2O2-challenged), and Asp (basal diet+2% Asp, H2O2-challenged). Our results showed that both Glu and Asp supplementation improved testicular morphology and decreased the genital index in the H2O2-treated boars. Glu and Asp administration increased the antioxidant enzyme activities and affected the testicular inflammatory cytokine secretion but had no effect on sex hormone levels. Furthermore, the mRNA expression of CAT, CuZnSOD, and GPx4 was altered in the testes and epididymis of boars treated with Asp and Glu. Glu and Asp supplementation also modulated the expression of TGF-ß1, IL-10, TNF-α, IL-6 and IL-1ß in the testis and epididymis. These results indicate that dietary Glu and Asp supplementation might enhance antioxidant capacity and regulate the secretion and expression of inflammatory cytokines to protect the testes and epididymis of boars against oxidative stress.

Effects of Bacillus subtilis DSM32315 supplementation and dietary crude protein level on performance, gut barrier function and microbiota profile in weaned piglets1.

Seventy-two piglets aged at 25 d were chosen to investigate the effects of Bacillus subtilis DSM32315 supplementation in diets with different protein levels on growth performance, intestinal barrier function, and gut microbiota profile in a 42-d trial. The animals were allotted to four treatment groups in a randomized complete block design involving a 2 (protein levels) × 2 (probiotic levels) factorial arrangement of treatments. Two protein levels included the high CP (HP) diets (0 to 14 d, 20.5%; 15 to 42 d, 19.5%) and the low CP (LP) diets (0 to 14 d, 18%; 15 to 42 d, 17%), and added probiotic (PRO) levels included at 0 and 500 mg/kg diet. Two interactions between CP and PRO for ADG (P < 0.01) and F/G (P < 0.05) were observed in phase 1. Within the piglets given the LP diet, probiotic supplementation increased ADG and decreased F/G ratio. Likewise, there were interactions between CP and PRO on the digestibility of CP (P < 0.01) and EE (P < 0.05), and probiotic supplementation increased the digestibility of CP and ether extract (EE) of piglets fed with LP diet, but that was not the case for piglets fed with HP diet. Furthermore, there were interactions between CP and PRO on villus height (P < 0.01) and villus height:crypt depth ratio (P < 0.05) in ileum. Piglets fed with LP diet containing probiotic had the greatest villus height and villus height:crypt depth ratio in ileum among treatments. There were also main effects of PRO on the propionic acid (P < 0.05) and butyric acid (P < 0.05), and the concentrations of propionic acid and butyric acid in colonic digesta were increased with the inclusion of probiotic in diet. Piglets fed with LP diet containing probiotic had the greatest population of Bacillus and Bifidobacterium (P < 0.05) in colon. In addition, there were interactions between CP and PRO on the mRNA expressions of occludin-1 (P < 0.05), epidermal growth factor (EGF) (P < 0.05), and insulin-like growth factor 1 receptor (IGF-1R) (P < 0.05). The LP fed piglets plus probiotic exhibited the greatest mRNA expressions of occludin-1, EGF, and IGF-1R in ileum compared with other treatments. In conclusion, moderate dietary protein restriction combining with the addition of B. subtilis DSM32315 synergistically increased growth performance, altered hindgut bacterial composition and metabolites, maintained intestinal barrier function in ileum of piglets.

Prevention of Oxidative Stress by α-Ketoglutarate via Activation of CAR Signaling and Modulation of the Expression of Key Antioxidant-Associated Targets in Vivo and in Vitro.

α-Ketoglutarate (AKG) can act as an antioxidant both in vitro and in vivo. However, the mechanisms of the protective effects of AKG are still not well understood. We evaluated the effects of AKG supplementation on the regulation of the constitutive-androstane-receptor (CAR) pathway in porcine intestinal cells and piglets exposed to H2O2. Our data showed that AKG treatment significantly increased not only the intra- and extracellular levels of AKG (26.9 ± 1.31 µmol/g protein, 1064.4 ± 39.80 µmol/L medium) but also those of Asp (29.3 ± 0.21 µmol/g, 4.20 ± 0.11 µmol/L), Gln (24.82 ± 1.50 µmol/g, 1087.80 ± 16.10 µmol/L), and Glu (91.90 ± 3.6 µmol/g, 19.76 ± 1.00 µmol/L). There was approximately a 4-fold increase in α-ketoglutarate dehydrogenase mRNA levels in enterocytes and a simultaneous reduction in ROS levels ( P < 0.05). Moreover, AKG treatment increased the activities of the antioxidant enzymes and the efficiency of cellular respiration ( P < 0.05). AKG also regulated the mRNA levels of the target genes involved in antioxidant responses and xenobiotic detoxification in enterocytes. Increases in the protein levels of SOD1, SOD2, CAR, RXRα, and UCP2 and marked reductions in the expression levels of Nrf2 and Keap1 proteins ( P < 0.05) were observed after AKG administration in the H2O2-induced piglets. Our results indicated that AKG may protect against oxidative stress by activating CAR signaling and modulating the expression of key antioxidant-related targets, which improves cellular respiration and antioxidant capacity. The in vivo and in vitro effects of AKG suggest that it may prove to be useful in the reduction of oxidative stress in animal and human trials and subsequent prevention of gastrointestinal pathologies.

Efficacy and safety of Suanzaoren decoction for primary insomnia: a systematic review of randomized controlled trials.

BACKGROUND: Insomnia is a widespread human health problem, but there currently are the limitations of conventional therapies available. Suanzaoren decoction (SZRD) is a well known classic Chinese herbal prescription for insomnia and has been treating people's insomnia for more than thousand years. The objective of this study was to evaluate the efficacy and safety of SZRD for insomnia. METHODS: A systematic literature search was performed for 6 databases up to July of 2012 to identify randomized control trials (RCTs) involving SZRD for insomniac patients. The methodological quality of RCTs was assessed independently using the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Twelve RCTs with total of 1376 adult participants were identified. The methodological quality of all included trials are no more than 3/8 score. Majority of the RCTs concluded that SZRD was more significantly effective than benzodiazepines for treating insomnia. Despite these positive outcomes, there were many methodological shortcomings in the studies reviewed, including insufficient information about randomization generation and absence of allocation concealment, lack of blinding and no placebo control, absence of intention-to-treat analysis and lack of follow-ups, selective publishing and reporting, and small number of sample sizes. A number of clinical heterogeneity such as diagnosis, intervention, control, and outcome measures were also reviewed. Only 3 trials reported adverse events, whereas the other 9 trials did not provide the safety information. CONCLUSIONS: Despite the apparent reported positive findings, there is insufficient evidence to support efficacy of SZRD for insomnia due to the poor methodological quality and the small number of trials of the included studies. SZRD seems generally safe, but is insufficient evidence to make conclusions on the safety because fewer studies reported the adverse events. Further large sample-size and well-designed RCTs are needed.

Dietary L-arginine supplementation differentially regulates expression of lipid-metabolic genes in porcine adipose tissue and skeletal muscle.

Obesity is a major health crisis worldwide and new treatments are needed to fight this epidemic. Using the swine model, we recently reported that dietary L-arginine (Arg) supplementation promotes muscle gain and reduces body-fat accretion. The present study tested the hypothesis that Arg regulates expression of key genes involved in lipid metabolism in skeletal muscle and white adipose tissue. Sixteen 110-day-old barrows were fed for 60 days a corn- and soybean-meal-based diet supplemented with 1.0% Arg or 2.05% L-alanine (isonitrogenous control). Blood samples, longissimus dorsi muscle and overlying subcutaneous adipose tissue were obtained from 170-day-old pigs for biochemical studies. Serum concentrations of leptin, alanine and glutamine were lower, but those for Arg and proline were higher in Arg-supplemented pigs than in control pigs. The percentage of oleic acid was higher but that of stearic acid and linoleic acid was lower in muscle of Arg-supplemented pigs, compared with control pigs. Dietary Arg supplementation increased mRNA levels for fatty acid synthase in muscle, while decreasing those for lipoprotein lipase, glucose transporter-4, and acetyl-coenzyme A carboxylase-α in adipose tissue. Additionally, mRNA levels for hormone sensitive lipase were higher in adipose tissue of Arg-supplemented pigs compared with control pigs. These results indicate that Arg differentially regulates expression of fat-metabolic genes in skeletal muscle and white adipose tissue, therefore favoring lipogenesis in muscle but lipolysis in adipose tissue. Our novel findings provide a biochemical basis for explaining the beneficial effect of Arg in improving the metabolic profile in mammals (including obese humans).

Dietary L-arginine supplementation increases muscle gain and reduces body fat mass in growing-finishing pigs.

Obesity in humans is a major public health crisis worldwide. In addition, livestock species exhibit excessive subcutaneous fat at market weight. However, there are currently few means of reducing adiposity in mammals. This study was conducted with a swine model to test the hypothesis that dietary L-arginine supplementation may increase muscle gain and decrease fat deposition. Twenty-four 110-day-old barrows were assigned randomly into two treatments, representing supplementation with 1.0% L-arginine or 2.05% L-alanine (isonitrogenous control) to a corn- and soybean meal-based diet. Growth performance was measured based on weight gain and food intake. After a 60-day period of supplementation, carcass and muscle composition were measured. Serum triglyceride concentration was 20% lower (P < 0.01) but glucagon level was 36% greater (P < 0.05) in arginine-supplemented than in control pigs. Compared with the control, arginine supplementation increased (P < 0.05) body weight gain by 6.5% and carcass skeletal-muscle content by 5.5%, while decreasing (P < 0.01) carcass fat content by 11%. The arginine treatment enhanced (P < 0.05) longissimus dorsi muscle protein, glycogen, and fat contents by 4.8, 42, and 70%, respectively, as well as muscle pH at 45 min post-mortem by 0.32, while reducing muscle lactate content by 37%. These results support our hypothesis that dietary arginine supplementation beneficially promotes muscle gain and reduces body fat accretion in growing-finishing pigs. The findings have a positive impact on development of novel therapeutics to treat human obesity and enhance swine lean-tissue growth.

Cryptotanshinone protects primary rat cortical neurons from glutamate-induced neurotoxicity via the activation of the phosphatidylinositol 3-kinase/Akt signaling pathway.

Excitotoxicity contributes to neuronal death and is involved in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). In the present study, cryptotanshinone, an active ingredient from a Chinese plant, Salvia miltiorrhiza, was investigated to assess its neuroprotective effects against glutamate-induced toxicity in primary culture of rat cortical neurons. Cryptotanshinone reversed glutamate-induced neuronal toxicity, which was characterized by decreased cell viability, increased lactate dehydrogenase release, neuronal DNA condensation, and the alteration of the expression of Bcl-2 family proteins. The neuroprotective effects of cryptotanshinone could be blocked by LY294002 and wortmannin, two inhibitors of PI3K. The importance of the PI3K pathway was further confirmed by the activation of Akt and anti-apoptotic Bcl-2 by cryptotanshinone in a PI3K-dependent manner. These results suggest that cryptotanshinone protects primary cortical neurons from glutamate-induced neurotoxicity through the activation of PI3K/Akt pathway. Such neuroprotective effects may be of interest in AD and other neurodegenerative diseases.

[Clinical investigation of conservative treatment for volar Barton fracture].

OBJECTIVE: To discuss the indication and outcome of volar Barton fracture treated by nonoperative method. METHODS: Twenty-three cases of volar Barton fracture treated by closed method included 8 male and 15 female with an average age of 52.2 years,ranging 16 to 84 years. Among them, 16 cases showed subluxation of the carpus (15 cases were Mehara type I ,1 case was Mehara type III) by radiographs except the other 7 cases. By the experimentation in 32 cadavers, the injury of dorsal radiocarpal ligament was supposed to be a very important cause of the subluxation of the radiocarpal joint. The criteria of Pattee and Thompson was used to evaluate the outcome of the treatment. RESULTS: Twenty-three patients were followed up for 7 to 70 months, 11 cases gained satisfactory outcome (1 case as excellent, 10 cases as good), 12 cases gained unsatisfactory outcome (5 cases as fair, 7 cases as poor). Five of 7 cases without the subluxation of the carpus by the radiographs gained satisfactory outcome. Six of 16 cases with the subluxation of the carpus gained satisfactory outcome. CONCLUSION: (1) The result of reduction will influence the outcome of the treatment, the step on articular surface shoud be less than 2 mm after reduction. (2) Nonoperative method is recommended if volar Barton fractures are not associated with subluxation of the carpus. (3) Nonoperative method can be tried first if the fractures associated with the subluxation of the carpus, however operation is recommended when the articular step is more than 2 mm.

Cytotoxic diterpenoids and sesquiterpenoids from Pteris multifida.

Three new ent-kaurane diterpenoids, named pterokaurane M 1-M 3 ( 1- 3) and three new C 14 pterosin-sesquiterpenoids, named multifidoside A-C ( 4- 6), along with 18 known compounds, were isolated from the whole plants of Pteris multifida . The structures of 1- 6 were established using spectroscopic methods, including extensive 2D NMR and CD analyses. Compounds 4 and 5 showed cytotoxicity against the HepG2 tumor cell line with IC 50 values of less than 10 microM.