Uridine alleviates high-carbohydrate diet-induced metabolic syndromes by activating sirt1/AMPK signaling pathway and promoting glycogen synthesis in Nile tilapia (Oreochromis niloticus).

Carbohydrates have a protein sparing effect, but long-term feeding of a high-carbohydrate diet (HCD) leads to metabolic disorders due to the limited utilization efficiency of carbohydrates in fish. How to mitigate the negative effects induced by HCD is crucial for the rapid development of aquaculture. Uridine is a pyrimidine nucleoside that plays a vital role in regulating lipid and glucose metabolism, but whether uridine can alleviate metabolic syndromes induced by HCD remains unknown. In this study, a total of 480 Nile tilapia (Oreochromis niloticus) (average initial weight 5.02 ± 0.03 g) were fed with 4 diets, including a control diet (CON), HCD, HCD + 500 mg/kg uridine (HCUL) and HCD + 5,000 mg/kg uridine (HCUH), for 8 weeks. The results showed that addition of uridine decreased hepatic lipid, serum glucose, triglyceride and cholesterol (P < 0.05). Further analysis indicated that higher concentration of uridine activated the sirtuin1 (sirt1)/adenosine 5-monophosphate-activated protein kinase (AMPK) signaling pathway to increase lipid catabolism and glycolysis while decreasing lipogenesis (P < 0.05). Besides, uridine increased the activity of glycogen synthesis-related enzymes (P < 0.05). This study suggested that uridine could alleviate HCD-induced metabolic syndrome by activating the sirt1/AMPK signaling pathway and promoting glycogen synthesis. This finding reveals the function of uridine in fish metabolism and facilitates the development of new additives in aquatic feeds.

Bacillus cereus Alters Bile Acid Composition and Alleviates High-Carbohydrate Diet-Induced Hepatic Lipid Accumulation in Nile Tilapia (Oreochromis niloticus).

A high-carbohydrate diet (HCD) can induce excessive fat accumulation in fish, and intestinal microbiota are thought to play important roles in host metabolism. Whether and how intestinal bacteria alleviate the HCD-induced metabolic disorders in fish have attracted more attention. Bacillus cereus was isolated from the intestine content of Nile tilapia. The control diet, high-carbohydrate diet (HC), and HC supplemented with B. cereus Su1 (HCS) were used to feed juvenile Nile tilapia for 8 weeks. The results of the present study showed that B. cereus Su1 supplementation decreased the serum glucose, triglycerides (TG), and reduced hepatic lipid accumulation compared with the HC group. The intestinal bacterial composition analysis suggested that HCS elevated bacterial diversity and the enriched bacteria were closely related to bile acid (BA) metabolism. Higher bile salt hydrolase (BSH) activity was found in the HCS group and B-targeted metabolomic analysis revealed that HCS increased BA content in the intestine and liver compared with HC, including unconjugated BAs (CA and CDCA) and conjugated BAs (TCA, GCA, TCDCA, GCDCA, TDCA, and TUDCA). Furthermore, a high-carbohydrate diet supplemented with B. cereus Su1 significantly enhanced the protein expression of the BA receptor farnesoid X receptor in the liver and decreased significantly the expression level of lipid synthesis-related genes and proteins, while it had no significant effect on lipolysis-related genes and proteins. This study found that B. cereus Su1 altered the intestinal microbiota and bile acid content and composition to regulate the lipid metabolism, revealing the function of the crosstalk among probiotics, intestinal microbiota, and BAs in ameliorating lipid accumulation induced by a high-carbohydrate diet in fish.

Mechanically controllable nonreciprocal transmission and perfect absorption of photons.

Photon absorption and nonreciprocal photon transmission are studied in a rotating optical resonator coupled with an atomic ensemble. It is demonstrated that the perfect photon absorption is accompanied by optical bistability when the resonator is static. If the spinning detune is adjusted to some particular values, we find that the amplified unidirectional photon transmission can be realized. We have explicitly given the perfect photon absorption conditions and the maximal adjustable amplification rate. It is found that the coupling of the resonator and the atomic ensemble is necessary for perfect photon absorption, and the phase difference of the two input fields only affects the perfect absorption point. It gives new insight into the design of photon absorbers and optical switches.

Influence of dietary sodium taurocholate on the growth performance and liver health of Nile tilapia (Oreochromis niloticus).

Bile acids (BAs) are a class of cholesterol-derived amphipathic molecules approved as new animal feed additives. However, the functional researches mainly focused on BAs mixture, and the influence of the individual BA on fishes was still limited. In the present study, Nile tilapia were fed basal diet with three levels of sodium taurocholate at 0 mg/kg (CON), 300 mg/kg (TCAL), and 600 mg/kg (TCAH) for 8 weeks. The results indicated that addition of sodium taurocholate did not significantly influence the growth performance. Instead, TCAH group had higher cholesterol accumulation with liver fibrosis. In TCAH group, the level of nuclear factor E2-related factor 2 (nrf2) signaling-associated oxidative stress factors significantly increased in the liver. Additionally, fish in TCAH group had the highest expression level of genes encoding endoplasmic reticulum (ER) stress and inflammatory cytokines in the liver. In conclusion, 300 mg/kg of sodium taurocholate did not significantly influence the growth performance of fish, while 600 mg/kg of sodium taurocholate markedly induced cholesterol accumulation and liver injury, suggesting that the application of taurocholic acid in aquafeed should be re-evaluated.

Bacillus amyloliquefaciens protects Nile tilapia against Aeromonas hydrophila infection and alleviates liver inflammation induced by high-carbohydrate diet.

Carbohydrates are widely distributed in nature as an important nutritional substance and energy source. However, the utilization efficiency of carbohydrates is very poor in fish. Over consumption of carbohydrates will cause excessive inflammatory response and result in lower pathogen resistance in fish. Probiotics have been widely used to prevent inflammation, but the underlying mechanism still needs more exploration. In this study, three diets, including a control diet (CD), a high-carbohydrate diet (HD) and the HD supplemented with Bacillus amyloliquefaciens SS1 (HDB) were used to feed Nile tilapia for 10 weeks. At the end of the feeding trial, fish were challenged with Aeromonas hydrophila (A. hydrophila) for 7 days. The data showed that the addition of Bacillus amyloliquefaciens SS1 (B. amyloliquefaciens SS1) significantly increased the survival rate and enhanced the respiratory burst activity of head kidney leukocytes in Nile tilapia. B. amyloliquefaciens SS1 treatment significantly elevated the anti-oxidative capability, which was evidenced by higher activities of superoxide dismutase (SOD) and total antioxidant capacity (T-AOC), and higher content of reduced glutathione (GSH) in the serum. Administration with B. amyloliquefaciens SS1 effectively suppressed inflammatory response in the liver by inhibiting nuclear factor kappa-B (NF-κB)/interleukin-1 beta (IL-1ß) inflammatory signaling pathway. In vitro analysis suggested that intestinal bacteria derived-acetate has the antioxidant capability, which may account for the alleviation of inflammation. Overall, this study demonstrated that dietary supplementation with B. amyloliquefaciens SS1 protected Nile Tilapia against A. hydrophila infection and suppressed liver inflammation by enhancing antioxidant capability.

Lactobacillus plantarum Ameliorates High-Carbohydrate Diet-Induced Hepatic Lipid Accumulation and Oxidative Stress by Upregulating Uridine Synthesis.

The overconsumption of carbohydrates induces oxidative stress and lipid accumulation in the liver, which can be alleviated by modulation of intestinal microbiota; however, the underlying mechanism remains unclear. Here, we demonstrated that a strain affiliated with Lactobacillus plantarum (designed as MR1) efficiently attenuated lipid deposition, oxidative stress, as well as inflammatory response, which are caused by high-carbohydrate diet (HC) in fish with poor utilization ability of carbohydrates. Serum untargeted metabolome analysis indicated that pyrimidine metabolism was the significantly changed pathway among the groups. In addition, the content of serum uridine was significantly decreased in the HC group compared with the control group, while it increased by supplementation with L. plantarum MR1. Further analysis showed that addition of L. plantarum MR1 reshaped the composition of gut microbiota and increased the content of intestinal acetate. In vitro experiment showed that sodium acetate could induce the synthesis of uridine in hepatocytes. Furthermore, we proved that uridine could directly ameliorate oxidative stress and decrease liver lipid accumulation in the hepatocytes. In conclusion, this study indicated that probiotic L. plantarum MR1 ameliorated high-carbohydrate diet-induced hepatic lipid accumulation and oxidative stress by increasing the circulating uridine, suggesting that intestinal microbiota can regulate the metabolism of nucleotides to maintain host physiological homeostasis.

Microbiota derived butyrate affected the muscle texture of Nile tilapia (Oreochromis niloticus) fed with different protein sources.

Flesh quality is influenced by diet components, but the underlying mechanism remains unclear. This study aimed to investigate the effect of replacing soybean meal (SBM) protein with cottonseed protein concentrate (CPC) at different levels (0%, CK; 15%, CPC15; 30%, CPC30 and 45%, CPC45) on the flesh quality of Nile tilapia. The results indicated that different protein sources influenced muscle amino acid composition instead of fatty acid composition. Lower muscle lipid content was found in CPC45, which in turn significantly altered the muscle texture. The hepatic lipid metabolism-related genes were detected and we found that CPC45 significantly suppressed the lipogenesis and promoted lipolysis. Higher content of microbiota-derived butyrate was found in the intestinal content of CPC45 and butyrate could decrease the lipid accumulation in vitro. Replacing SBM with CPC increased the intestinal butyrate to suppress the lipogenesis in the liver which may account for the increased muscle hardness.

Sarsasapogenin-AA13 inhibits LPS-induced inflammatory responses in macrophage cells in vitro and relieves dimethylbenzene-induced ear edema in mice.

Sarsasapogenin-AA13 (AA13) is a novel synthetic derivative of sarsasapogenin extracted from the Chinese herb Rhizoma Anemarrhenae. In this study we investigated the effects of AA13 on lipopolysaccharide (LPS)-induced production of inflammatory factors in macrophage cells and the anti-inflammatory activity of AA13 in an inflammatory model of dimethylbenzene-induced ear edema. Macrophage cells (RAW264.7 cells and mouse peritoneal macrophages) were exposed to LPS (1 µg/mL); pretreatment with AA13 (5-20 µmol/L) dose-dependently inhibited LPS-induced production of NO, TNF-α and PGE2, and LPS-stimulated expression levels of COX-2 and iNOS. Furthermore, pretreatment with AA13 dose-dependently suppressed LPS-stimulated phosphorylation of p38 and JNK, but had no effect on ERK in RAW264.7 cells. Moreover, pretreatment with AA13 inhibited LPS-induced activation of the nuclear factor (NF)-κB in RAW264.7 cells. The in vivo anti-inflammatory activity of AA13 was demonstrated in a mouse inflammatory model: pre-treatment with either AA13 (20 mg·kg-1·d-1, ig) or a positive control antifani (10 mg·kg-1·d-1, ig) for 3 d significantly relieved dimethylbenzene-induced ear edema. Our results demonstrate that AA13 effectively inhibit LPS-induced inflammatory responses in macrophage cells in vitro and relieve dimethylbenzene-induced ear edema in vivo.

Up- regulation of miR-328-3p sensitizes non-small cell lung cancer to radiotherapy.

MicroRNAs (miRNAs) are believed to be resistant against radiotherapy in certain types of cancers. The aim of our study was to determine the clinical application of miRNAs in non-small cell lung cancer (NSCLC). Sixty NSCLC tissue samples and adjacent histologically normal tissues were obtained for miRNAs microarray analysis and validated by RT-qPCR. Correlation between miRNA expression level and clinicopathological features was evaluated. Our study examined the influence of changed miRNA expression on the damaged DNA and its associated radio sensitivity. Luciferase assay was performed to determine potential effects on the targeted gene. Our study identified fifteen altered miRNAs in which miR-328-3p was down regulated in NSCLC tumour tissue as compared to normal tissues. Down-expression of miR-328-3p was positively associated with an enhanced lymph node metastasis, advanced clinical stage and a shortened survival rate. miR-328-3p expression was decreased in A549 cells compared to other NSCLC cell lines. Up-regulation of miR-328-3p demonstrated a survival inhibition effect in A549 and restored NSCLC cells' sensitivity to radio therapy. An increased miR-328-3p expression promoted irradiation-induced DNA damage in cells. γ-H2AX was identified as the direct target of miR-328-3p. Over-expressed miR-328-3p can improve the radiosensitvity of cells by altering the DNA damage/repair signalling pathways in NSCLC.

Calpain-Calcineurin-Nuclear Factor Signaling and the Development of Atrial Fibrillation in Patients with Valvular Heart Disease and Diabetes.

Calpain, calcineurin (CaN), and nuclear factor of activated T cell (NFAT) play a key role in the development of atrial fibrillation. Patients with valvular heart disease (VHD) are prone to develop atrial fibrillation (AF). Thus, our current study was aimed at investigating whether activation of calpain-CaN-NFAT pathway is associated with the incidence of AF in the patients with VHD and diabetes. The expressions of calpain 2 and alpha- and beta-isoforms of CaN catalytic subunit (CnA) as well as NFAT-c3 and NFAT-c4 were quantified by quantitative reverse transcription-polymerase chain reaction in atrial tissues from 77 hospitalized patients with VHD and diabetes. The relevant protein content was measured by Western blot and calpain 2 in human atrium was localized by immunohistochemistry. We found that the expressions of calpain 2, CnA alpha and CnA beta, and NFAT-c3 but not NFAT-c4 were significantly elevated in the samples from patients with AF compared to those with sinus rhythm (SR). Elevated protein levels of calpain 2 and CnA were observed in patients with AF, and so was the enhanced localization of calpain 2. We thereby concluded that CaN together with its upstream molecule, calpain 2, and its downstream effector, NFAT-c3, might contribute to the development of AF in patients with VHD and diabetes.

[Effect and mechanism of gastrodin inhibiting ß-amyloid plaques in brain of mice].

This study was designed to investigate the effect of gastrodin（GAS） against ß-amyloid plaques in 5×FAD Alzheimer's disease（AD） transgenic mice, and utilize 117 cell model（over-expression of Aß and ß-secretase） to explore the underlying mechanism. 5×FAD mice model were randomly divided into three groups, including GAS-high dose group(GAS-H, 200 mg·kg(-1)·d(-1)), GAS-middle dose group(GAS-M, 100 mg·kg(-1)·d(-1)) and GAS-low dose group(GAS-L, 50 mg·kg(-1)·d(-1)). Meanwhile, the wild type mice were used in the control group. After being treated with GAS for three months, 5×FAD mice were evaluated by Morris water maze for the learning and memory ability and by ELISA for Aß in the cerebral homogenate. Then, Aß plaques in the hippocampus and cortex of 5×FAD mice were observed and analyzed with immunohistochemical staining. The cell apoptosis rate and the cell viability were determined in vitro, after the cells were treated with different concentrations of GAS(10, 25, 50 and 100 µmol·L(-1)). Furthermore, Intracelluar/extracelluar Aß were determined by ELISA. Effects of GAS on BACE（ß-secretase site APP cleaving enzyme） m RNA and protein expression were analyzed in 117 cell models by Q-PCR and Western blotting. The results suggest that GAS is able to restore the learning and memory capacity of 5×FAD mice, and reduce Aß in the cerebral homogenate and Aß plaques in the brain. Compared with the untreated transgenic positive group, Aß plaques were declined in hippocampus and cortex of GAS-H group by 93.28% and 88.88%, and Aß was reduced in the cerebral homogenate by 55.74%. In vitro study suggests a dose-dependent effect of GAS in reducing Aß in 117 cell models. When the cells were treated with 100 µmol·L(-1) GAS, extracelluar Aß and intracellular Aß of 117 cells were reduced by 63.1% and 49.1%. BACE expression was largely suppressed in m RNA by 32.9%（P < 0.01）. At 50 µmol·L(-1) GAS, the protein level was declined by 47.9%（P < 0.05）. In conclusion, GAS inhibits Aß production and accumulation by inhibiting ß-secretase.

Adiponectin receptor 1 (ADIPOR1) rs1342387 polymorphism and risk of cancer: a meta-analysis.

Many studies have indicated possible associations between a polymorphism of adiponectin receptor 1 (ADIPOR1) rs1342387 and risk of cancer, but contradictory results have been reported. The main aim of this study was to draw a reliable conclusion about the relationship between the rs1342387 polymorphism and cancer incidence, by conducting a literature search of Pubmed, Embase, Wanfang and Cochrane libraries. Eleven studies including 3, 738 cases and 4, 748 controls were identified in this meta-analysis. The ADIPOR1 rs1342387 polymorphism was associated with risk of colorectal cancer for all genetic comparison models (GG vs AA, OR: 1.44, 95%CI: 1.21 -1.70; G carriers vs A carriers, OR: 1.23, 95%CI: 1.11 -1.36; dominant model, OR: 1.28, 95%CI: 1.10 -1.49 and recessive model, OR: 1.31, 95%CI: 1.12 -1.55). Stratified by ethnicity, the rs1342387 polymorphism was significantly associated with risk of colorectal cancer in Asian ancestry for all genetic comparison models (GG vs AA, OR: 1.56, 95%CI: 1.26-1.92; G carriers vs. A carriers OR: 1.30, 95%CI: 1.18 -1.43; dominant model OR: 1.31, 95%CI: 1.08 -1.60 and recessive model OR: 1.44, 95%CI: 1.26 -1.64), but not in Caucasian or mixed (Caucasian mainly) groups. In summary, the ADIPOR1 rs1342387 polymorphism is significantly associated with risk of colorectal cancer among individuals of Asian ancestry.

Proteolysis by endogenous calpain I leads to the activation of calcineurin in human heart.

BACKGROUND: The calmodulin-independent pathway is thought to involve the activation of calcineurin by calpain. However, the effect of endogenous calpain on calcineurin in human heart is not well known. METHODS: Proteolysis and activation of recombinant calcineurin by purified calpain isozymes I and II as well as endogenous calcineurin by calpains in the human heart were investigated by Western blot. Activation of calpain and calcineurin in the human heart was examined using zymography and a calcineurin activity assay. RESULTS: Calpains I and II caused limited proteolysis of full-length calcineurin in a Ca(2+)-dependent manner, and the degradation fragment(s) were constitutively active in the absence of calmodulin. Calpain I and calcineurin were expressed in ventricular myocardium from patients with heart failure, with no difference in expression levels in the left and right heart chambers. Human heart calpains I and II degraded the specific substrate casein in gels which were incubated in medium containing Ca2+, but not in Ca(2+)-free medium. Calpain inhibitor-sensitive calcineurin activity was stimulated in the human ventricular myocardium in the presence of concentrations of Ca2+ that were found to activate calpain I. CONCLUSIONS: Proteolysis of calcineurin A by endogenous calpain I leads to the formation of constitutively active calcineurin in the human heart, which may contribute to the pathogenesis of myocardial disease.

[Correlation of adiponectin gene SNP +45T/G polymorphism and premature coronary heart disease of Han ethnic males].

OBJECTIVE: To examine the relationship between single nucleotide polymorphism (SNP) of adiponectin (APN) locus +45T/G and Han male patients with premature coronary artery heart disease (pCAD). METHODS: A total of 423 male patients of Han ethnic group (< 55 yr old) undergoing coronary arteriography were recruited. Among them, 358 patients were diagnosed as pCAD while another 65 normal control (NC). All subjects were genotyped for adiponectin gene SNP +45 by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: Statistical differences of TG/GG genotype ratio were observed between two groups. The TG/GG genotype ratio in the pCAD group was 51.1% versus 35.4% in the NC group (χ(2) = 5.45, P = 0.022). After an adjustment of conventional risk factors, such as age, body mass index (BMI) and hypertension, the adiponectin gene SNP +45TG/GG genotype was strongly associated with Han ethnic group male pCAD by binary logistic regression analysis (OR = 1.843, P = 0.035, 95%CI: 1.045 ∼ 3.250). And there were statistical differences between TT genotype and TG/GG genotype among pCAD subjects in the following factors: BMI, total cholesterol (TC), low-density lipoprotein-C (LDL-C) and APN level (P < 0.05). By Pearson correlation analysis, APN was negatively correlated with TC, LDL-C and SNP +45T/G polymorphism. CONCLUSION: The SNP of adiponectin locus +45T/G is associated with male pCAD. And TG/GG genotype is a possible predisposing gene for Han ethnic group male pCAD.

[Effects of carvedilol and metoprolol on expression of autoantibodies against cardiac adrenergic receptors in aged patients with chronic heart failure and ventricular arrhythmia].

OBJECTIVE: To investigate the effects of carvedilol and metoprolol on the expression of autoantibodies against cardiac ß(1), ß(2) and α(1) adrenergic receptors in aged patients with chronic heart failure (CHF) and ventricular arrhythmia (VA). METHODS: Sixty-eight patients with CHF and VA were randomly divided metoprolol treatment group or carvedilol treatment group on the basis of digoxin and diuretic treatment. All patients were followed up for six months cardiac function was monitored by echocardiography, VA by Holter and the three autoantibodies by enzyme-linked immunosorbent assay (ELISA). RESULTS: (1) Systolic blood pressure and brain natriuretic peptide (BNP) were significantly lower in carvedilol group than that in metoprolol group (P < 0.05). (2) The positive ratio of autoantibodies against the cardiac ß(1) adrenergic receptor was significantly decreased compared with that of pre-treatment (P < 0.05) in metoprolol group. The positive ratios of autoantibodies against cardiac ß(1), ß(2) and α(1)-adrenergic receptors were all significantly decreased compared with that of pre-treatment (P < 0.01) in carvedilol group. Moreover, the incidence of VA was significantly decreased in carvedilol group (P < 0.05) but not in metoprolol group. CONCLUSION: Carvedilol is superior to metoprolol on decreasing the incidence of VA in aged patients with chronic heart failure and ventricular arrhythmia.

Characterization of H5N1 influenza viruses that continue to circulate in geese in southeastern China.

The H5N1 influenza virus, which killed humans and poultry in 1997, was a reassortant that possibly arose in one type of domestic poultry present in the live-poultry markets of Hong Kong. Given that all the precursors of H5N1/97 are still circulating in poultry in southern China, the reassortment event that generated H5N1 could be repeated. Because A/goose/Guangdong/1/96-like (H5N1; Go/Gd) viruses are the proposed donors of the hemagglutinin gene of the H5N1 virus, we investigated the continued circulation, host range, and transmissibility of Go/Gd-like viruses in poultry. The Go/Gd-like viruses caused weight loss and death in some mice inoculated with high virus doses. Transmission of Go/Gd-like H5N1 viruses to geese by contact with infected geese resulted in infection of all birds but limited signs of overt disease. In contrast, oral inoculation with high doses of Go/Gd-like viruses resulted in the deaths of up to 50% of infected geese. Transmission from infected geese to chickens occurred only by fecal contact, whereas transmission to quail occurred by either aerosol or fecal spread. This difference is probably explained by the higher susceptibility of quail to Go/Gd-like virus. The high degree of susceptibility of quail to Go/Gd (H5N1)-like viruses and the continued circulation of H6N1 and H9N2 viruses in quail support the hypothesis that quail were the host of origin of the H5N1/97 virus. The ease of transmission of Go/Gd (H5N1)-like viruses to land-based birds, especially quail, supports the wisdom of separating aquatic and land-based poultry in the markets in Hong Kong and the need for continued surveillance in the field and live-bird markets in which different types of poultry are in contact with one another.